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·Systemic Arterial Embolism Pathogenesis and Prophylaxis

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·MODERN MEDICAL MONOGRAPHS
14
Systemic Arterial Embolism
Pathogenesis and Prophylaxis
By solNTÁRTIN ASLEY, MD
a sociale Clinical Profes or of Medicine
Unnersuy of Southern California
School of Medicine
GRUNE & STRATTON
19
NEW YORK AND LONDOV

·B Fic 1 & Vural thrombi in rheumatic mitral ten B (angrene of che lege following repeated embolism to bifurcation of aorta in theumatic mitral stenaşıs with gangrene Death from cerebral embolism (By permi sion of Dr RS Guillan and Dr N F Freeman San Francisco ·Contents IX PREFACE INTRODLCTION Å HISTORICAL KEVIEW The Problem Terminology 9 1 HEART DISEASE AS 4 CALCE OF ARTERIL. EXIBOLISY Di tribution of Cardiac Mural Clots Incidence and Di tribution of Erbol. m 16 Fmbolic versus Thrombotir Occlusion 2 DEATH AND DISABILITY FRO\E SYSTEVIE ARTERIAL FROU MIN 20 HEART DISEASE 20 Mobilization of Cardiac Vlural Thrombi 21 Ceneral Dan er of Death 21 Monalny in Single Eysodes Cerebral Fmbolism 22 23 Aortic Embolism Arterial Emboli m in the Extremties 23 Death and Di ability Following Embolectomy 23 Portality in Survivors 26 Duration of Survival Period after Recognized Embolim Recurrent Emboli ta as Cave of Death 27 The Period of Greate RA Recurrent Etisalı m Repeated Embolectomy 29 3 CLINICAL CORRELATIONS OF CARDIAC Vítkel THROMBOSIS AND SYSTEMIC ARTERIAL EMBOLISH 33 Rheumatic Hart Disease Auricular Fibrillation and Right Heart Failure in Rheumatie Vitral Stenc is Con ge tive Heart Failure and Left Auricular Thrombı Mitral Stenosis and Leit Auricular Thrombs Auricular Fib Tillation and less Auricular Thrombosis Mural Steno 19 ver us Aurkular Fibssllaljo E timating Danger of Sy temie Arterial Fmbolism The Chance of Leit Auricu lar Thrombos Chincal Correlations of Lelt Ventricular Thromba Character Location and Size of the Ventricu lat all le lon 4 PATHOCYNESIS OF VASCULAR THRONEO is 17 Thrombotic Sumulus of Dama ed End(thelium 47 Stasis of Flow Coagulability 49 Laboratory tests 5ATHOGENESIS OF CARDIAC MLBSL THROBOSIS Left Auskulat Tarombosis in Rheumatic Heart Disease 53 53 Significance of Auricular Fibrillation leit Ventricular (Mural) Thrombos 6 PATHOCETESİş OF SYSTIC ARTERIAL EXBOLIŞW 3 EART DISTASE 58 Vol 1lization of Cardiac Varal Thrombi 61

·the funds condense and form ma ses which
solidify, it is thus that Nature has sowed in the
agents which are the principles of life the secret of
our destruction It is particularly in the heart that
the fluids coagulate Hoating polypi may plug the
arteries their mass may carry them into vanous
spots and cause various accidents
JEAN BAPTISTE DE SENAC (1749)

·Pieface FOR A CLINICAN TO IMSADE «O controversial a field of medicine as that of thromboembolish with too definite opinions would eem presumplu ous Many crucial deci ions in treatment, however are ba ed on pre sumptive endence which can only be a ceased clinically Periodically he u tas emble analyze and cru talſize the evidence into a mordable hs pothesis to guide bus therapy even though additional evidence may within the following weeks sender certain aspects of his hypothesis also lete Many other truths must be learned belore ne con non rather than FUA$ the pathogenesis and proper treatment of setemic arterjal embo- Iu.m Certain logical deductions however can at present be drawn from available evidence This book attempt to prevent the pertinent material which I have derived much plex urs from arcumulaling and collasing The ullingness to help promptly hown by colleagues was heart warmyn My Strend to orer a quarter of a century De Grorge H Houck is directly respon able for the book s genesis and was con tantly available for help Many colleagues read certain chapters and contributed constructive criticisms I am especially grateful to Doctors Myron Prinzmetal Gurth Carpenter Howard P Lewy Joha / Tragerman Marcus A hrupp and CA Peter on My as octates in practice Dorso s Wilham P Kroger Clifford B Cherry Pobert Curridge ACP Balos and Ben Pin hy gase timely encouragement and vegetons and my brother Dc F Vincent Aley intermittently applied a helpfu) goad ben indu try lagged Dr Charles Dotter and Dr Israel Steinl er: were helpful ia locating angiocardio graphic evidence of left auricular thrombos which was courteou ly upplied by Dr LA Soloff and Dr Zatuchni Dr Arthur Bloomfield and Dr Ralph Major read and criticized the ki torical seslex Permis ion to u e illu trations was gene usls sisen by many and 19 acknowledged in the undis dual illu trations Yr Zolton Iuhasz made what I consider beautiful illo trabon The colored photographs nete made available by Dz S Gilflap and Dr Norman E Freeman The mla ion of the color plates was made po ible by the generosity of my ·CONTENTS Mobilization of Thrombı from the Left Auricle 62 Rheumatic Mitral Stenosis Rhythm Exertion Digitalis Arteriosclerotic Heart Ds case 66 Mobilization of Left Ventricular Thrombi 68 7 DIFFERENTIAL DIAGNOSIS OF RUFUVATIC AND ARTERIOSCLEROTIC HEART DISEASE Incidence of Unsuspected Rheumatic Heart Di ease 73 Pathologic States of Theumatic Heart Disease 74 Clinical Diagnosis of Rheumatic Heart Di ease 80 Causes of Error in Diagnosis Auricular Fibrillation in Middle Age Diagnosis of Mitral Stenosis Roent genologic Study Flectrocardiographic Changes Pre sumptive Diagnosis Recognition of Embolism 01 Recording Pul es Angiocardiograply Subacute Bacterial Endocarditis after Middle Age 8 PROTHYLACTIC ANTITHIROVIBOTIC MEASURES FOR SYSTEMIC ARTERIAL EMBOLISTI 99 Rlieumatic Fever 99 Available Antithrombotic Measures Clioice of Anti thrombotic Measures Arteriosclerotic Heart Disease III Effect of Dicumarol on Formation of Ventricular Mural Thrombi Prophylactic Use of Dicumarol in Acute Myocardial Infarction Value of Dicumarol in Good Risk Ca es Danger of Dicumarol Therapy in Myo cardial Infarction Program of Treatment for Good Risk Patients Congestive Heart Failure 117 9 CONTINUOUS ANTITHROUBOTIC DRUG THERAPY IN HEIRT DISEASE Factors Aflecting Dicumarol Therapy Danger of Bleeding (Minor and Vajor) Protective Level in Chronic Cardiovascular Disea e Treatment Followin, Acute Fmbolic Occlusion 12) Treatment for Surynors of Embohsm 220 Tests of Prothrombin Activity 127 Choice of Antitrombotic Drug 127 Selection and Education of Patient 128 Laboratory Control Printed Instructions Guien Dicu marol Patients Discontinuance of Dicumarol 133 Results from Dicumarol Beſare and During Operation 133 Antithrombotic Preparation for Operation 39 BIBLIOGRAPHY 151 I\DF 119 121 ·Infroduction THE PROBLEM SYSTEMIC ARTERIAL EMBOLISH 15 a dread complication of any heart disease in which thrombı form in the cardiac cavities of the left de A high proportion arise from rheumatic heart disease Such embolim usualls is an un-u pected and unpredictable event The first clinical evidence usually is an occlusion of a large artery Surgical removal of an occluding clot from the aorta or the arteries of the legs occa ionally may be a life-aving procedure but is not ditected at the cause Further more embolism amenable to surgical treatment constitutes only a mall proportion of the total in the va t majority the occluded artery 1 inaccessible This e pecially applies to embolism of the cerebral arteries The number of patients who die of are disabled with the first recog nued embolic attack is distre.. ingly high. Many who urvive the first recognized epi ode survive at the cost of an amputated leg if the embolic occlusion i in a peripheral artery or of a paralyzed ide at the occlusion occurs in an artery in the brain The srvivors then face a trong likelihood of further di ability or of death from a recurrent emboli m Fven the be t treatment, if applied after an embolus to an artery 15 recognized is often tragically delayed and becomes a treat ment of frustration Satisfactory management must be preventive and deal with the problem much earlier Effective treatment mut be directed either at prevention of formation or of mobilization of the canitary cardiac thrombs In rheumatic heart di ease there has been a long preceding period during which the substrate factors which culminate in embolism have been developing We know little about either the precise pathogenesis (f the formation or the mechan; m of mobilization of left auricular thrombı The pathologic stage apparently has been set for years before the appearance of thrombi The period between the time of formation of a left auricular thrombus and the time of its eventual ejection as a recognized sy temic arterial embolus is clinically a latent period The time of formation of left ventricular thrombı not accurately predictable such throrabi occur in relation to the acute or chronic ·X PREFACE friends Mr David Buttolph and Nir Ashton Castle Dr Frederick J Moore helped with evaluation of statistical data Mrs Margaret Stevenson, with Dr John C Jones permisyon made essential statistics available My secretaries Grace Munk Hilda Harris and Pauline Conkle and my laboratory technician Esther Anspoker, spent many hours assisting me The help of Leon Lukaszewski of the Audio Digest Foundation was invaluable For a physician to overlook the many hours of companionship gra ciously foregone by his wife would be unforgivably remiss I acknowl edge her indulgence with gratitude and affection JOIIN MARTIN ASKEY MD ·Introduction THE PROBLEM SYSTEMIC ARTERIAL ESIBOLISM is a dread complication of any heart disease in which thrombı form in the cardiac casilics of the left side A hoh proportion an e from theumatic heart disease Such embolism usually is an unsu pected and unpredictable esent The fir t clinical evidence u ually is an occlusion of a large artery Surgical removal of an occluding clot from the aorta or the arteries of the legs occa ionally may be a liſe aving procedure but is not directed at the cause Further more embol m amenable to urgical treatment consulutes only a small proportion of the total in the va t majority the occluded arlery 15 inacce sıble This e pecially applies to emboli m of the cerebral arteries The number of patients who die or ate di abied with the fir t recog nized embolic attack is du tres ingly high. Many who survive the fir ! recognized epi ode urvie at the cot of an amputated leg iſ the embolic occlusion is in a peripheral artery or of a paralyzed de if the occlu ion occurs in an artery in the brain The survivor then face a strong likelihood of further disability or of death from a recurrent embol m Even the be t treatment iſ applied after an embolus 10 an artery is recognized is often tragically delayed and becomes a treat ment of frustration Satisfactory management mut be preventive and deal with the problem puch earlier Effective treatment must be directed either at prevention of formation or of mobilization of the cavstary cardiac thrombi In rheumatic heart di ease there has been a long preceding period during which the substrate factors which culminate in embolism hase been developing We know little about either the precise pathogene 19 of the formation or the mechanim of mobilization of left auricular thromb: The pathologic stage apparently has been set for years before the appearance of thrombı The period between the time of formation of a left auricular thrombus and the time of its eventual ejection as a recognized systemic arterial embolus is clinically a latent period The time of formation of lelt sentrxular thrombi is not accurately predictable such thrombi occur in relation to the acute or chronir ·2 SYSTEMIC ARTERIAL EMBOLISM endocardial damage of myocardial infarction or congestise licart fatlure There is no reliable way as yet to tell which individual has a small clot in the heart although angiocardiography promises help in the near future If a thrombus is present no one can predict accurately whether or when it will be di-lodged, or if di lodged, where it will occlude an artery A recognized embolic attach, unfortunately, is the first overt clinical evidence of a thrombus in the left cardiac cavities The chance of a cauitary thrombus being pre ent the likelihood of its mobilization as an embolus, and the rik of death or di ability in any individual, at present can only be evaluated statistically Any pro phylactic treatment of the indkidual at present must depend on such statistical data The natural history of systemic arterial embolism must be carefully studied Evidence has been accumulated to allow an appraisal of the hazard to the indivdual The unavoidable challenge to the physician is the need for evaluation of the quantitat en l of a temic arterial emboll m before an occlusion of a larger artery has occurred The first three chapters will discus the problem of the risk the morbidity and mortality and the clinical correlations of sy temic arterial embolism Chapters 4 5 and 6 di cuss the pathogenesis of cardiac mural thrombosis and systemic arterial embolism Chapters 7 8, and I consider the diagnostic and proplıy lactic measures adu able at present in attacking the problem These chapters attempt to blend fact and theory into workable indications for treatment. The evolution of knowledge regarding thromboembolism prior to the pre-ent era will be gren in the Historical Review TERMINOLOGY The term aurcle" will refer to the entire inſlow cavity from either the greater or le ser circulation The clinicians term body of the auricle and auricular appendage, will be used in preference to the anatonii ts terms atrium and auricle 'The former fcrme arc sc}} understood The latter terme uc believe are confusing to the American and Engli h clinician By this latter nomenclature the term aurice' applies only to the auricular apprendage To avoid confusion the term auricle has been abandoned by tho e u ing thus nomenclature The atrial appendage has been introduced the consonant icrms 'atrial fibrillation and atrial thrombı lave been employed in feud of auricular fibrillation and auricular thrombi The wisdom of such term ·3 INTRODUCTION nomeni lature is questioned by many for the monograph therefore we shall u e the old terminology On the other hand the new term antithrombotic will be frequently employed as one at times more precise than the term anticoagulant Pratt 19% believes that emphasis should be pared on the deaurable rather than the undesirable a pects of treatment We believe it mean ing is clear and its use acceptable The tudy of theumatic heart disea e 18 esentially a tudy of rheumatic mitral valvular disea e with or without aortic valvular disea e Most authors base not uprluded cak hed nodular aortic stenos! in their reports although Claw on " * believes it constitutes 10 per cept of all rheumatic valvular lesions The mitral salse has been involved in well over 90 per cent of the ra es reported as rheumalıc lieart disease Among the many terms for the surgical correction of delormuts of the mitral valve onfice ne prefer the term mitral vals oplats It kems to describe better an operative procedure which mu! con der not only correcting deformites of the vale leaflet but at times o pla tic correction of the papılları muscle and the chordae lendineae ·Historical Review ONLY AFTER MANI CENTURIFS of observation have ne ei oled the concept--now so casually accepted-that blood clots form during life in the cavities of the heart and often di charge emboh which occlude the systemic arteries Indeed, there was a lapse of nearly two thousand years from the first recognition of vascular thrombosis in viso to the time when it was established that this clotting process could take place within the heart itself It apparently was Senac 10 u ho in 1749 first described arterial embolism, but only in the last century has the embolic tendency been clearly traced to its two chief cause thrombosis in the left auricle due to rheumatic fever and thrombosis in the left sentricle due to myocardial infarction Hippocrates and his son in lau Diocles of Carystu (1 observed coag ulation in the blood vessels during hfe and as Greek they had a word for t-thrombos Galen 8 later agreed that the humor congeal actually in its own surroundings he Latınized the word to thrombus, but contributed nothing to the concept His dogmatism o dominated thinking that it was not until the early 16th century that cardiac clot or polyps as he called them, were described by Bennen " He and all other physicians considered all clots as hrung been formed during life and this misinterpretation led to nearly two centuries of mistaken in cardiac diagnosis Kerckering 136 in 1670 first pointed out that cardiac clois actually can form after death but he then fell into completely oppo ite error and further confused the picture by stating that all heart chamber clots were postmortem and utterly insignificant It was not until 1749 that an unusually brilliant physician thought through the problem The was Jean Baptı te de Senac 18 whose concept of thromboembolism anticipated in all essential points the current concept generally credited to Virchow 53 As repeatedly happens in medicine his valid concepts not upported by sufficient evidence gained no recognition But regardles of his failure to convince his contemporaries Senac should be credited with three accomplı hments First he clearly differentiated true or antemortem clots or polyps from ſal e or postmortem clots Fale polyps he recognized are 4 ·S HISTORICAL REVIEW tho e concretions that form at the end of an illness or after death true polyps are tho e nhich have formed a long time before the patient dies Fibrous adherent texture he noted was the di linguzelung char acteri tic of true clots they were hard elastic tenacious membranoue and yellowish poly pod bodies He added come are o tightly bound to the sub tance of the ventricle that one almost cannot detach them from it. Senac s second achievement was to describe clearly the three pre requisites for true clot formation--that i, tasis damage to the learl wait and coagulability Polyp he and have a predilection for areas where blood flow is arre ted As soon as movement of the circulation of the blood is topped the blood must condense He thus «poke of the pause uhich the blood makes in the heart When the blood does not empty it elf or when the contractions are incen ble or when there is some ob tacle in the pulmonary artery or in the aorta in the auricles or the ventricles then blood pels barriers it tends to coagulate Particularly in the inter tices of the columna the blood flow 13 asre ted (all ialus mine! The description these fore rlearly applies to the thrombotir milieu of the left aurcle in mitral tenosi Just as clearly Senac recognized that slasis was ond one of the necessities to polyp formation which tended to occur only where the internal surface becomes uneven hy sotne lesion or ome tearing clotting did not tend to occur on mooth polished urface And finally he recognized that the occurrence and the ize of the clots depended on the coagulability of the blood which saried in diferent conditions. In certain allnetes its di alved There are other lineales in which the blood is more di pored to coagulate Thrombos18 was umitsated he knew in the white h matter of the blood Blood he ays does not coagulate as cheer does that is to say as a uniform matter This lymphatic element was the first to coagulate as a white clot which enme hed the red cells If the blood Row was rapid the clots remained white but if the action of the blood is feeble he noted the red parte *ill be sefamed in great quantity and a red clot would form This is the pre ent concept as to the pathogenesis of white platelet thrombi and red thrombs ) Senat described several palients with blood as white as milk and said such blood coagulates ex ils according to sarious observations ·6 SYSTEMIC ARTERIAL EMBOLISM 9 147 To thus clear exposition, Senac added a third achievement Ile de scribed embolism from cardiac clots to the sy temic arteries He de scribed attached clots and those which were 'floating These floating polyps " he said 'may occupy various places at various times, they may plug the artery in other circumstances the mass may carty it elf into various spots and cause various accidents" Why so little attention was paid to this simple mechanistic theory of thrombosis and embolism is difficult to understand Physicians did not distingui h true from fal e clots and continued to rely on any clot in the heart as a felicitous explanation for any difficult case Morgagni '7 writing 12 years after Senac's publication, lamented the stultifying cffect of the accepted doctrine 'If in the heart of the body after death have been found a polypus, thus was immediately said to have ersted from the beginning of the disorder and to have been the perpetual author of all his cviis Consart,"2 in 1806 even believed that he was the first clearly 10 differentiate betx cen antemortem and postmortem clots and later on Laennec gave him the credit They either disregarded or were igno rant of Senac s work Senac s mechanistic concept was overshadowed in the first half of the 19th century by the almost unnersally accepted bchef that vascular inflammation wuth exudation caused all thromboss and later by Rokitan kys theory bluch ascribed all thrombous 10 or poisoned state of the blood The theory of humoral pathology says Acherknecht? appeared to contemporaries as ultra modern progre sic and scientific Arrhythmia was carly associated with polyps but by a natural error the polyps were considered the cause of any erregularites inter mittencies or inequalities of the pul e occurring in their presence This association was emphasized soon after Beniveni firat ob crved clots in the heart Senac (who perhaps is better known becau e he reported the value of quinine for rebellious pulptoljon ) found uneven ness of the pui e to be the most reliable son of cardiac polyps The great Laennec 14. in the hustoric De L Auscultation Mediate aupported this causal relation though he made the incredible statement that the polyp could be localized when the pulse was irregular on one side of the heart and regular on the other Hope in 1812 nanted among the general signs of polypi of the heart the pulse is small wcal irregular intermittent and une qual It seems lughly probable that in most instances these de criptions referred to auricular fibrillation crasis 117 ·7 HISTORICAL REYIEW Thus up to a little oser 100 years ago it was acrepted that clots could form during hile in the cavities of the heart and, characteristically Here I..giated with an irregular action Honever the location of the clots was not correlated with any particular lesion It till was not recognized that most clots in the left auricle occur in mitral vals ular disea e while tho e in the left ventrirle u ually result from endomyo cardial Decrosis due to coronary occlu ion Oddly mo I reported thrombo were in the roght sentricle De pite the recognition by Senac in 1719 that polyps tend to form in the heart when the blood meets barners and Vieu ens 5 earlier description in 1715 of mitral teno is with its obvious ob truction to blood flow over a century and a half passed belore the high incidence of leit auricular clots was generally accepted Osler in his first edition (1893: esy It is not uncommon at the examination to find white throrbe in the appendix of the left auricie Occasionally a large part of the auricle 15 occupied by an antemortem thrombus The predilection of thrombosis for the patches of roughening on the posterior wall of the auru le was aptly described in 1910 by San. om* who noted their importance as a source of sy temic arterial emboli The endocardium luming the auncle as u ually thickened in many Lases in pa ches by chronic endocarduis or atheromalous change The pos error wall of the auricle is most frequently thus afected on the Internal surface of this part of the auricle coagula are frequently obserted They may become detached and become embol which are arrested at ome part in the arterial channeis A correlation of lek auricular thrombosis with mitral stenosis and wall lessons as a ource of embolism thus was establı hed by 1910 Is 1021 MacCallum ' emphasized the frequency of these roughened areas and they became known as MacCallum > patches although he did not correlate these patches with thrombo 19 All this was pro 1243 certainly but while the characteristic lesions a ociated with left aurk ular thrombosis were thus being identified the connection between thrombosis and arrhythmia kas fading into the background in 0 less hir : editsop although the frequency of left auricular thrombs 13 emphasized no correlation with anhythmia js noted Rapid and uregular action of the heart is correlated only with failure of compensation but not with mitral steno 3 and not with clots This omis ion was dot made good eles no ler s ejohth edition of 1918 by which time the arrhythmia had been identified at antul ·8 SYSTEMIC ARTERIAL EMBOLISM fibrillation Although clinicians in the 1920 s showed increasing aware ness of this relationship, it was not until 1930 that Harvey and Levine !!! after studying 21 instances of uninfected niural thrombı (31 with auricular fibrillation), concluded, "there can be no doubt that auricular fibrillation increases the incidence of thrombus formation within the auricles Other investigators concurred and in 1941, when Hay and Levine 11" analyzed 186 cases to determine the relatie importance of age and auricular fibrillation in the development of auricular mural thrombı, they found that fibrillation was the effective factor, regardless of age nor Libman 153 The association of mural clots with coronary arterial dı-case became recognized about 50 years ago, when Huchard' i observed thrombı attached to areas of infarchon However, neither he nor anyone elc recognized that there thrombz discharged emboli to peripheral arteries He described embolism to the brachial and the left internal carotid arteries without revealing any suspicion as to their origin in their early reports on coronary thrombosis neither Herrick 11 mention embolism as a complication One of the fir t reports on thi subject was that of Paullin appearing in 192) 19 Following a scverc attack of coronary insufhciency and occlusion the patient s leg became painful then pale and clammy The pulse could not be felt below the popliteal artery At necropsy a mural thrombus was found in the left ventricle and Paullin “uggested that apparently a portion of the thrombus had been dislodged and had plugged the right femoral artery Since that time arterial embolism in myocardial infarction has become well recognized and greatly feared ·ܢܝܕ Heart Disease as a Cause of Arterial Embolism THE FOLR BANY CAUSES of sistemic arterjal emboli m are Theumatic heart disease myocardial infarclion chronic arteriosclerotic heart dis eace and subacute bacterial endocardit The proportion of ca e attributed to each cau e depends on the accuracy of diagnosie and many estimates of the causes of emboli m were pos ibis Inaccurate in earlier urveys The differential diagnosis of arteriosclerotic heart disea and rheumatic heart disease in the last decade has been more precise and the frequency of rheumatic heart di ea e in middle age and in thn aged has been more readily recognized This may help to explain some discrepancies in estimates Among 228 instances of peripheral arterial emboliem ob erved between 1928 and 1917 Hamonica (FIC 2) found that is 41 (19 pxos cent) the diagno is was arteriosclerotic heart disease ard in 72 (32 per cent) it was acute myocardial infarction--a total therefore of si per cent attributed to arteriosclerotic heart di ea e In In 212 came of embolic arterial occlusion surveyed by Flasher and Stephen on between 1910 and 1930 145 (69 per cent) were considered auricular in origin and only 50 (23 per cent) ventricular Arterio clerotic heart disease therefore was diagnosed only half as frequently as in the earlier urves Even before the advent of penicillin therapy subacute bacterial endo card tas cau ed only a mall proportion of systemic arterial em) oben y per cent, according to laimovici s tudy already cited and only 3 per cent in Flasher and Stephen ons later ca es? Other causes of arterial emboli m are stah: tically rare Ventricular mural thrombosis caused by thickening of the endocardium mucurs tau conditions termed endocardial fibroelastosis of recurrent parietal thromboendocarditze and can cause arterial embolism Tha caUe 1 unknown with possibly both infiammatory and nutritional factors achse 4 mall proportion of arterial embols are unassociated with any prosen heart disease they may anse from atheromatous plaques in the aorta from thrombi in aneury ma from pulmonary veins OT 9 ·8 SYSTEMIC ARTERIAL EMBOLISM fibrillation Although clinicians in the 1920s showed increasing aware ness of this relationship it was not until 1930 that Harves and Levine 1:1 after studying 11l instances of uninfected mural thrombı (31 with auricular fibrillation), concluded there can be no doubt that auricular fibrillation increases the incidence of thrombus formation within th auricles' Other investigators concurred and in 1941, when Hay and Levine 11analyzed 186 cases to determine the relative importance of age and auricular fibrillation in the development of auricular mural thromb they found that fibrillation was the effective factor, regardle s of age The as ociation of mural clots with coronary arterial di case became recognized about 50 years ago, when Huchard 1 1 ob eried thrombi attached to areas of infarchon However, neither he nor anyone ele recognized that these thrombı discharged embol to peripheral arteries He described embolism to the brachial and the left internal carotid arteries without revealing any auspicion as to their origin in their early reports on coronary thrombosis neither Herrick 11 nor Libman 233 mention embolism as a complication One of the first reports on this subject was that of Prullin appearing in 1921 190 Following a csere attack of coronary insufficiency and occlusion the patient leg became painful then pale and clammy The pulse could not be felt below the popliteal artery At necrops; a mural thrombus was found in the left ventricle, and Paullin suggested that apparently a portion of the thrombus had been dr lodged and had plugged the right femoral artery Since that time arterial embolism in myocardial infarction has become well recognized and greatly feared ·11 HEART DISEASE AS A CAUSE OF ARTERIAL EMBOLISM TABLE 1-Distribution of Thrombz in the Carities of the Left Side of the Heart in Patients Dying of Rheumatic Heart Disease Aumber of thrombi in left auric? or left sentricle Aumber ofibrombi Per cent in in del sprcle Beit uncle Author 56 >8 Goder trom 064 9 9 100 D Harley and I evine 22 20 Garyuy 900 Total 89 85 92 3 The danger of sy temic arterial embolum ari ing from cardiac mural thrombı can be measured more accurately than that of pulmonary probohsin Whereas pulmonary embolism may aree from thromo orig?32{ag is either the peripheral veins or the right auricle, tomnc arterial emboli ma arises in over 90 per cent of cases frora throni in the left heart In rheumatic heart di ease almost all these (TABLF 1) thrombı are in the left auricle (90 per cent of mural thrombı are found there) in sonrheumatic beart disea e the majority of thrombı in the left heart are in the left sertricle 3 DISTRIBUTION OF CARDIAC MURAL CLOTS It is a reasonable premise that the source of thrombopla tin intrating A thrombus is in its immediate nmghisorhood This source in casitary thrombosis of the heart 38 adjacent damaged endothelium The location TABLE. -Disenburon of 199 Auricular Thrombi in Monrheumatic Heart Disease and Rheumatic Heast D sease honheumatic hear disP2P Per ceat Rheumatic heart do ea p Per cent P ht at cle 65 10 16 27 20 I tght and left Lei ausicle 17 29 19 15 33 25 I tal 132 Irom Sodet trom ·10 SYSTEMIC ARTERIAL EMBOLISM from the rare phenomenon of paradoxical embolism, in which embol pass through a patent foramen ovale or interventricular septum The infrequency of these causes is indicated by the fact that Haimovic tound no mention of them in huis 228 cases Wright Urdaneta and Wright, -77 in studying 107 cases of abdominal vortic aneurysm men tion no embolic complications PULM ARTERY PULMONARY VEIN THROMBOSIS 09% PATENT FORAMENE OVALE L AURICLE RHEUMATIC CHRONIC CARDIOVALVULAR DISEASE 404% RT AURICLE SUBACUTE BACTERIAL ENDOCARDIYIS 4 8% ARTERIOUCLEROTIC HEART DISEASE 193% RT VENTRICLE L VENTRICLE ACUTE MYOCARDIAL INFARCT 31 5 VENTRICULAR MURAL THROMBUS FIG 2 Origin of emboli 228 unselected cases of embolism of the eviremi ties (31 per cent undetermined) By permission from Harmouci H Pe ripheral arterial embol Angiology (February 1990) Paradoxic or crowed embolism may be cusprcted of arterial embolem OCLUTS in the absence of obuous cardiac disea e and there has been thrombophlebitis and repeated pulmonary infarction 143 The diagnosis is made more often at necropsy than during life Tumor embolism is usually a diagnosis made by microscopic examina tion but massive tumor embols have been described in the brain the spleen the kidney the lungs the later and the extremities Clots in the pulmonary veins may rarely rause arterial emboliem ·13 HEART DISEASE AS A CAUSE OF ARTERIAL EMBOLISM necrops, however, among 160 cases of either recent or remote mso cardial infarction 73 (40 per cent) had a total of III peripheral infarcts The du tribution of sj temic arterial erboh m was studied by Dalry and associates 3 in a large series of ca es of theumatic heart di 74 TABLE 3 and FIGURE 3 Their estimate reflects experience in practice and TARLE 3-Dutribu on of Arterial Systemic Fmbolism in Rheumatic Hear! Diskose Bosed on Clinical Dia roses * Site of lodgment of 393 embolt occurring in 191 ponents Site Number Total Per cent 188 47 8 182 2 3 56 14 z 11 17 28 Arteries to the brain Cerebral Carotid Basılar Relinal Arteries to the abdominal viscera MIA enteric Splers Renal Aortic bifurcation Iliac arteries Arteries to the lower extrettyfies Femoral Popliteal Tibial Arteries to the upper extremities Axillary Brachial 23 59 22 5 3 66 16 8 29 21 16 39 10 0 3 36 Tiał 393 100 D From Daley Ry et a! Sy tem c Arterial Embols mit in Rheumatic Heart Disea e Am Ile st 3 Oriotes 10al by permi sion probably approximates the true distribution The mot frequest ites of lodgment they found are the brain the extremities and the abdom inal vicera ikidneys spleen and intestinesj Olesen 179 found a similar distributica among 123 embol in 75 Theumatı patients Jordan Miller Edwards and Parker 13 studied 372 patients with acute and healed ·12 SYSTEMIC ARTERIAL EMBOLISM of these potential sites for thrombı determines the d, tribution in all ous heart diseases wall lesions in nonrheumatic heart disease are pre dominantly in the left ventricle and right ayrıcle, in rheumatic heart drease, in the left auricle The presence of stasis in these areas encour ages thrombosis The segregation of clots of nonrheumatic origin in the right auricle and left ventricle is quite definite Among 192 instances of auricular clots studied by Soderstrom (TABLE 2) - 3 in 82 the under lying lesion was of a coronary 'type Seventy nine of the 82 were in the right auricle Among 26 instances of auricular thrombı with under lying lesion was of a coronary type Seventy nine of the 82 were in auricular clots were found in groas nonrheumatic heart disease, the underlyina lesions were predominantly rheumatic Myocardial infarc tion is the chief cause of thrombus formation in the ventricles and its predominance in the left ventricle accounts for mo t left sentricular thrombi Over 90 per cent of all systemic arterial emboliem ari es in clots associated with either rheumatic heart disease or coronary arterial disease with or without hypertension Left auricular thrombı of rheu matic origin are presumed to be the cause of most recognized peripheral arterial embol Left ventricular thrombı account for most of the remainder The incidence of left auricular thrombi in rheumatic heart disease and of left ventricular thrombi in myocardial infarction aries 141th many factors and will be discussed later INCIDENCE AND DISTRIBUTION OF EMBOLISM The actual incidence of systemic arterial embolism in heart di ease is not accurately known Clinically detectable emboli represent only the major arterial occlusions and the necropsy examinations are unfortu nately numerically inadequate and necessarily often incomplete This is true whether the source be from rheumatic or arteriosclerotic heart. There is a discrepancy between clinical and pathologic diagnose and between suspected and actual emboli m Warren and Linton found at necropsy an incidence of emboli to the brain spleen and kidney considerablı higher than that derived from the clinical study Other studies confirm tha Based solely on clinical findings Ole cnl! diagnosed symte mic arterjal embol, m in 75 patients among 351 van outral stenosis (28 per cent) but found many unsuspected embol (mostly splenic and renal) at necropsy Hellerstein and Martin !!* found 185 in tances of clinically detected peripheral asterial orclu ion in 1605 compiled cases of myocardial infarction (11 5 per centi Ar ·15 HEART DISEASE AS A CAUSE OF ARTERIAL EMBOLISM myocardial infarction at necropsy and found the brain and kidnrya most frequently carolied by embol m Neither clinical nor necropsy diagno es gne accurate «tatı tical results hoxeres because many embola semain unrecognized Occlu joga of smaller arteries often are not even suspected, although they may cause many ague signs and ymptoms The mimicry of neurologic di orders in the legs by arterial occlu long has been reported by Gilfillar Jones Rolland and Wilies Many epi-odes of transitory faintness and dizziness or weaknese numbness and tingling of the extremitie repre eat minor cerebral emboli m Only a mall proportion of the emboh in 11 ceral arteries are recognized even major emboli in the kidner are unsuspected unle s they cause pain and hematuna and renal failure may be the result of renal infarction Hone and Coggin 1"found that renal infarction from vations sources as recogmed lclore Jeak in only two of 203 ca es, and er Burchell and Edwards s found chacał es scene is only one of 41 in tances of arterial emboliem ol the pleen and kidney associated with acute myocardial infarction Many emboli to the spleen and to the mpsenteric sessels cannot le diagno ed from igns and ymptoms The diagnostic dificulty in all there in tances is equal regardless of the source of embolu Emboli are more frequently su pected and diagnosed in the extremi ties than in the viscera because of visible ans and more obyanus symptoms Ba ed on the symptoms of udden pain or udden numbnes and culdne in 330 in tances of peripheral arterial emboli m studied hy Haimosici?" the diagno 19 was uspected in 81 2 per cent of 300 embolic occlusions 17 157 per cent) gave no clinical manifestation Warten and I inton reported udden onset in only 69 per cent of 110 in tances of embohem in the extremities and evere pain in only 3.& per cent Fren of all potential sites of arterial emboli in were erammed at necrops as they are not--notably the asteries of the brain and of the extremities- the findings would till not accurately rellent the incidence of ystemic arterjal embol m for arterial occlusions and peripheral infarcts often cannot be differentiated as to their origin erther embolx or forally thrombatic Although the brain is upposedly the commonest ite of embolism the case in which it is etamined are elected and therefore not typical-only 10 cases in 161 in a series hy Tess and Day 3 Graham et al % rez jewel a necropsy tudy n! peripheral in{atelit in 101 patients dying of rheumatic fieart dispac

·ARTERIES TO BRAIN
4763
CEREBRAL 18 2
- RETINAL 3
BASILARI
ARTERIES TO UPPER
CAROTID 2
EXTREMITIES 1004
AXILLARY 3
BRACHIAL 36
ARTERIES TO ABDOMINAL
VISCERA 14 %
SPLENIC 17
RENAL 26
MES ENTERIC II
AORTIC BIFURCATION
(23) 39%
ARTERIES TO LOWER
EXTREMITIES (66)
16.8%
ILIAC ARTERIES
(211 5.3%
FEMORAL 29
POPLITEAL 21
TIBIAL 16
Fic 3 Distribution of systemic arterial embolism in rheumatic heart
disease (Figures 3-5 reproduced by permi sion from Daley R et al
Systemic arterial embolism in rheumatic heart disease Am Heart J
October 1931 )

·15 HEART DISEASE AS A CAUSE OF ARTERIAL EMBOLISM tatı tical myocardial infarction at necropsy and found the brain and sineys mot frequently involved by emboli m Neither clinical nor necropsy diagno es gue accurate results however becau-e many emboli remain unrecognized Occlu 10ne of waller arteries often are not even su pected although they may cause many vague signs and symptoms The mimicry of neurologir disorders in the legs by arterial occlu tons has been reported by Gilfillan Jones Rolland and Wylie " Many epi odes of transitory laininess and dizziness or Weakneris numbnes and tingling of the extremitica repre sent minor crebral erhoh ma Only a mall proportion of the enbolt in v ceral arteries are recognized even major rmboli in the kidnese ate unsuspected unless they cause pain and hematuria and renal failure may be the re ult of renal infarction Horie and Comin1* found that renal infarction from various sources was recognized before death in only two of 205 ca es and Miller Burchell and Eduard 13 found clinical evidence in only one of 41 instances of arterial emboli m of the picen and kidney a hciated with arute myocardial infarction Many emboli to the pleen and to the me enteric yesmele cannot I» diagno ed from igns and siznitor The diaqno iu dilliculty in all these in carces is equal regardles of the source of embolu Embol are more frequently su pected and diagnosed in the cutremi Lies than in the vicera becau e of vi ihle 1904 and more obvious symptoms Based on the symptoms of udden pain or sudden numhne g and coldnes in 330 in tances of peripheral arterial embols m tudied by Harmonica V the diagno is was au pected on 12 per cent Of 300 embolic oclu ron 1(57 per cent i gave so clinical mapsfestation Warren and Lintor * reported sudden oneet in only 69 per cent of 110 in. tances of embolism in the extremitie and severe pain in only 228 per cent Esen of all potentialites of arterial emboliem were examined at neltog 1 they are not notably the arteries brain and of the extremities—the findings would till not accurately reflect the incidere of ystemic arterial emboli in for arterial scrlu sons and peripheral Infarcts often cannnt be differentiated as to their origin either embolic or locally thrombs tic Although the rain is supposedly the curton te demhalism the cars in winch it 19 examined are selected and therefore not typical-only 10 cases in 161 in a cries hy Weis and Dans 3 Gabam et al 195 reviene a necropsy study of peripheral infarction in 101 patients dying of rheumatic heart disease ·16 SYSTEMIC ARTERIAL EMBOLISM but did not mention the number of brains examined and Garvin 84 reported examination of the brain in only 56 per cent of his series Although the available cvidence is incomplete and inaccurate, still it indicates that the brain is the most frequent site of both fatal and nonfatal emboli, and any estimate of incidence based on eramınation which excludes this site must be considered inaccurate TABLE 4 Illus trates how experience of cerebral embolism varies according to specialty The pathologist obseries many asymptomatic cases (66 per cent) the TABLE 1-Incidence of Cerebral Embolism in Rheumatic Heart Disease Number of systemic Number of arterial cerebral embolisms embolisms Per cent 39 26 66 Method of diagno ing cerebral embolism Graham et al Weiss and Davis 57 28 49 Mecropay Clinical and pathologic Clinical Daley et al 393 188 48 Bourne 30 22 73 Clinical Warren Linton and Scannell 337 50 14 6 Clinical internist only those clinically manife-ted (48 49 and 73 per cent) and the surgeon predominantly those for whom an operation is being considered (14 6 per cent) EMBOLIC VERSUS THROMBOTIC OCCLUSION Unless an artery is seen at necropsy soon after occlusion it difficult to determine whether the cause was emboli m or thrombosis in aitu even the micro copic structure between the thrombus and the wall may yield no indication Differentiation must be based therefore on assumption If the evidence is equivocal and if either a thrombus or r significantly roughened area is found on the wall of the heart it is then assuined (not proved) that either a portion or an entire thrombus has been ejected and has caused the occlu ion By these criteria mo ! arterial occlusions tudied at necropsy after rheumatie heart disease ·17 HEART DISEASE AS A CAUSE OF ARTERIAL EMBOLISM have been judged embolic Daley et al found thrombi in the leit auricle in 23 of 39 palients with clinically diagnosed anenal emboli m and rou_hening of the wall in 6 others in four of five patients aged over 50 years with the ame diagnosis Glover O Meill fiarns and Janton 1 found thrombotic material in the left auricle Arterial occlusions a _ociated with acute or healed myocardial infarc tron however how by these criteria a much maller proportion of embolic occlu ions. Jordan et al 13 found that in only 29 of 52 instance (ou per cent) of vascular occlusion occurring in 210 patients with acute mayocardial infarction was there a corresponding cavitary clot o about half of the vascular occlusions in acute myocardial infarction ere pre sumably embolic The proportion of embolic ocrlusjons was much lower in tho e occlu ions as ocialed with healed infarcton« In only 8 of 32 instances (25 per cent) of vascular occlusions occurring in 127 patients with healed infarction was there a cavitary slot. Thu onl one in four va cular oclusions in healed myocardial infarctions na presumably embolic It is entirely rea onable that older individuale with arteriosclerotic disease should how a higher proportion of autoch thonous than of embonc vascular occlusions In Theumatic heart disea the average age is lower and there is less peripheral arterial decade It must be remembered however that an occlusion may be of embolic origin even though the pathologi t fails to find a thrombus in the left aurrcle The entire thrombus may have been extruded as implied by Graham et al in reporting the absence of left auricular thrombu un tho thurds of a series of peripheral infarcts found in patients with Theumatic heart di ease and as evidenced by case reports of similar findings followme arterial occlusions with typical embolt Another po sibility is that auricular thrombı may be mi ed by the pathologist Clots may be du lodged in the rourse of necrops Small emboli sulli cient to cau e disabling cerebral lesions can arise from small thrombi which lodged between the folds of tht trabeculae carneae can ea ily be mis ed Soderstrom alls the clots in the auricular appendage recess thrombi These are often of recent formation and characteristically die attarhed to the al by only a tiny stalk or not at all Conse quently he comments uch zhrombi asteasul; lo tor di lodged when thel ft auricular appendage is opened at autopay Wallach Lakash and Angrit s believe that nonbactenal thrombotic embols may aceount for a large proportion of emboli m in which there ·IB SYSTEMIC ARTERIAL EMBOLISM Is no evidence of left auricular thrombı, for in necropsies of 113 patients with rheumatic heart disease and infarctions of the hidney spleen, and brain, they found nonbacterial endocarditis in 28 per cent of those who had left auricular thrombi and in 52 per cent of tho e who died not They point out that the c Tegetations may be overlooked as a cause of embolism because they may Icare little gross evidence on being dılodged another possibility which must be considered there fore, in every instance of systemic arterial emboli m, even in rheumatic heart disease Calcific emboli following surgical mampulation of the mutral valic has been reported by various authors » Wers and Daus 13 reason ably maintain that the burden of proof us on those who deny that arterial occlusions in theumatic heart di ease are from left yuricular thrombı In the absence of definile localized arterio clerosis, a peripheral infarct in the umatic heart disea e 19 niore likely to be due to embolic Occlusion from a left auricular thrombus than to a thrombus in situ and should be so considered until this source is excluded This a umplion Would seem to be a wise precaution for ay ording a possible colly crror of omission in treatment Immediate surgical intervention is seldom necessary for an arteriosclerotic occlu ion but in embolic occlu ron of the artery to an extremity it inust be undertaken within a few hour A vascular occlusion in the presence of an acute or healed niyocardial infarction apparently is about as likely to be due to localized throm bosis as embolism Temporary obsery ihon justified and a careful differential diagnosis between embolism and thrombosis must be made SUMMARY Systemic arterial embolism ari en in over 90 per cent of cr cs cnther from clots in the Inkt auricle of rheumatic origin or clots in the left ventricle of arteriosclerotic origin Clols in the cardiac chambers are segregated according to the type of disease Whereas arterio clerol or coronary arterial dincase eau es lesions predominantly in the right ayricle and left ventricle rheumatic heart di et e causes lesions pre dominantly in the left auricle Rheumatic fieart disease is the mot frequent cius of systemin arterial emboliem Becau e of the urgency of treatment sy temic arterial occlusion in rheumatic heart di ease should in eers in lance be con sidered embolic in ongin unless another source is definitely establi hed ·HEART DISEASE AS A CAUSE OF ARTERIAL EMBOLISM 19 In arteriosclerotic heart de ea e hoxever the frequency of thrombotic vascular occlu ion makes a more deliberate differential diagno i* adva ble Although the incidence and di tribution of temie arterial embolism in heart di ea e are not accurately known the brain 14 apparently the mot frequent site of both fatal and nonlatal ) temic arterial embolism There are everal possibilities by which an arterial occlu ion may be of embolic origin even though no thrombus can be found in the left avricle ·2 Death and Disability from Systemic Arterial Embolism in Heart Disease MOBILIZATION OF CARDIAC MURAL THROMBI SINCE TIIE RISK OF DE ITII or disability from systemic arterial emboli in heart disease arıses only after mobilization of cautary thromb, the proportion of thrombı liberated is an important datum, but it is un known In no series of necropsies following death from heart disease has there been complete examination of all the possible arterial sites of embolism to correlate with the mural thrombi One of the most complete investigations of rheumatic heart disease has been that of Graham et al 101 who examined the brain in most of 101 necropaies Among 33 patients with thrombı in either the body or the appendage of the left auricle they found clear evidence of systemic embolism in 15 (45 per cent) The studies of these authors and others (TABLE 5) based on the identification of left auricular thrombı cither TABLE 5-Erdence Regarding Percentave of Left Auricular Thrombi Mobili ed in Rheumatic Ileart Disease (Number of | Number patients with with left systemic auricular arterial Per cent thrombi embolism mobilized Method of identifying thrombus Method of diagnosing systemic arterial embolism (raham 33 15 45 Necrophy Necropsy Necrops) Necropay Jordan et al 42 32 76 Clover et al 130 47 36 At commts surotomy Clinical 21 12 52 McCoon and Henly At comme surotomy Clinical (confirmed at autopsy) Total 226 105 46 20 ·DEATH AND DISABILITY FROM SYSTEMIC ARTERIAL EMBOLISM at operation or at necropsi and on the diagnosis of systemic arterial embolism from either clinical or pathologic findings indicate that in rheumatic heart di ease about half of all lett auricular thrombı are mobilized The same proportion applies to clots in all casities of the heart according to other tudies in * 114 13 GENERAL DANGER OF DEATH The danger from systemic arterial embolı m in rheumatic heart dis. case does not u ually appear until adulthood but then embolism accounts for a high mortality rate Hebbert and Rankın 15 found that among 45 patient. Over the age of 50 who died as a result of rheumatic heart disease 16 (3) per cent) died of major embolic incidents of 121 deaths directly attributed to theumatic heart di ease in patients between the ages of 40 and 80 Wallach et al 'found 42 (33 per cent) had died of embolism In addition ersboli m was indirectly responsible for other deaths--In one in tance bronchopneumonia had lollowed cerebral em bolistu Among 68 patients over the age of 40 who died of rheumatic heart disease Soloff and Zatuchni ascribed the deaths of 16 (23 per cent) to systemic arterial embolim Selzer 18 found 10 deaths from systemic arterial embolism among 9 necropay tudies where myocardial infarction was the primary illness Heller tein and Martin 11 ascribed 11 deaths annong 160 patients with myocardial infarction examined at necrop , &s being mainly due to systemic arterial embolism. In another li patients arterial embolism was a contabulory cau e of death MORTALITY IN SINGLE EPISODES Bigelow and Greenwood seported that of 39 rheumatic patients with #temic arterial embol, m even (17 per cent) died within a month after the fir embols m but they did not tate the location of the occlusion Twenty four per cent of 73 rheumatic patients studied by Ole en 1 died because of the first embolic episode Among 194 patients of Daley et al . with clinical diagnoses of 393 systemic arterial embals widely distributed the deaths of 23 (21 per cent) here the direct result of a single embolic epi ode From this compiled group of 308 patients with rheumatic heart disease with arterial embolism 49 (16 per cent) died as a re ult of a single epi ode The smmediate mortality rate from emboli m in myocardial infarction higher Jordan et al % report 8 25 per cent death rate in 81 patients with arterial embolism in acute or healed myocardial infarction The mortality rate in any study of ·22 SYSTEMIC ARTERIAL EMBOLISM systemic arterial embolism depends on the proportion of minor lo majo embol recognized, and must be related to the site of embol in The mortality rate in occlusion of a major artery is lugh, whereis immediate death does not often follow occlusion of a splenic, renal or brachus artery Fmbolism to a coronary artery, one of the rarent site, la per haps the luighest mortality (over 90 per cent) so CEREBRAL EMBOLISM Emboli m to a cerebral artery is the greatest danger from embolim in leart discase, because of its high incidence Next to the rarc coronari artery embolum it has the highest mortality rate and not only occount for the majority of embolic deaths but aluo causes servous se idual effects in half the prtients who do not die immediatel Tlie rihan anda crted by Harris and Levine s 109 report of immediate death in one tlued of 72 patients with rheumatic heart dı ease and the death of another 15 per cent within a period arcraging a little oser a year Drley sad that half the patients who had one or more cerebral einbolisme died from this complication Lenegre Tatıbouct and Paris 1 0 reported the death within a few days of more than a third of 83 patients with hemi plegra in rheumatic heart diner e and more or lesy cerere scquclu in a third of the survivors Rocdenbeck and Bermejo "however, reported immediate death of only one of 13 patients with hemiplegia Among the survivors hemiplegii may be followed by severe per sistent motor impairment with partial paralysı Several types of mental disturbance may des elop depending on the size and location of the encephalonulacia In 525 consecutie necropsics in a neurop ychiatric institution Toubin 19 found proof of recurrent cerebral emboli in as the cause of organic brain drcase in 17 patients although the cau e had been su-pected in only one Fue of the 17 patients had rlicumatic heart disease-dia, nosed before death in only one of them—2nd 230 of the five had had recurrent epileptic acizures Another had manic depressive psychosis and of the other two it was only stated that mental changes had been pre ent for many years Beundles the e five another of the 17 patients had nonbacterul thrombotic endocarditis The other 12 were patients with myocardial infarcts and ventricular mural thrombo Although improvements in operatne technic in mitral 17hoplits have reduced the incidence cerebral emboli m till remain one of the most ſcared complications of mitral sal oplasty " ·27 DEATH AND DISABILITY FROM SYSTEMIC ARTERIAL EMBOLISM AORTIC EMBOLISM Embol n to the bifurcation of the abdominal aorta fortunately com poses only about 5 per cent of the total sy temic arterial emboli in rheumatic heart disease Death or los of luxb occurs in a hugh pro portion 65 GO The mortality with aortic embolectomy is nearly as great as without 11.194 67 The pessimism of many surgeons is erprea ed by Taylor ! Successful aortic embolectomy 15 sa spectacular as to completely over hador its true medical worth it is fortunate that this procedure does not have to be con dered in the light of its general medical benefi Mankind would be far better erved if the ame time, effort and money would be spent on some dull public health problem It mut be noted however that many deaths following embolerton, are due to further embolism and not to the operation which u ually an indicated procedure ARTERIAL EMBOLISM IN THE EXTREMITIES Although emboh m to the extremities accurs in one fourth of all rheumatic patients with emboli m in only one half of thre (13 per cent of the total) so it usually dangerou These are the embolic orele nons of the femoral and alac arteries in embol mol the upper extremi ties medical treatment usually procures ati factory recovery but as to embolumn of the lower extremitie there is a «i le variation in reparted results as measured by mortality the frequency of gangrene ang residual di ability There is a good explanation for the variation The danger varies with the location the promptness and aptness of treatment, the condition of the cuculation and the likelihood of secur segre of embolism from the original source Impairment of collateral circulation by diffuse asterial damage or stasis due to congestive failure creates a morbid terrain for any arteriał ob truction Dye et al 07 attribute the poor results in their esses of embolectomes to the pre carious cardiac status of the patient. DEATH AND DISABILITY FOLLOWING EMBOLECTOMY The high mortality following even good treatment in advanced ca es 3*rident in the 1932 report br Flasher and Stephenson? of 212 patients at the Los Angeles County General Hospital Each of these had ·24 SYSTEMIC ARTERIAL EMBOLISM at least one embolic arterial occlusion affecting a lower extremt und 67 per cent died within 30 days of onset Although the patients selected for embolectomy were considered the better risks the mortalıtı among these was slightly higher~ 70 per cent In general however, the patients were in poor condition when first seen and the authors believed that "the outlook toward life and limb that we have noted certainly will not be as grim in private patients' In contrast Pratt 19 reports two thirds survival in 42 cases of embolism in the femoral artery Medical treatment has improved in the last decade and the re ults from emho lectomy hare improved with earlier operation and a better selection of patients In 83 patients without embolectomy for whom the treatment was considered "early and good Silbert records that 71 per cent recovered without gangrene Earlier embolectomy in a lugher proportion of cises was credited with an improvement in limb surual by Warren Linton and Scan nell © Although there can be lutte question that the early remos al of an embolus to the bifurcation of the aorta or the alzac or femoral artery is advisable still it is adv14able only if a trained surgeon anestheti and internist are available The prevention of the subsequent formation of a thrombus at the site of operation or of the inobilization of another left auricular thrombus is both an immediate and a remote concern The tragic nature of embolism to the extremitics in the past is well illustrated by a case report of over 80 years ago Treatment then was ill adv ed and futile and the patient usually died after mi erable suf fering The Yerbatim report is ghen here Embolism of the arteries the Extremities by Samuel B Hard MD AM - one of the Surgeons to the Pre byterian Hospital New York and Profes or of Surgery at the Woman s Medical College of the New York Infirmary The following case appeared in the writers practice la tummer and the rarity of such together with the poverty of the bterature of our own language on the subject are his rea ons for offering this paper for publication Ca e I Heart disease of Suteen ) ears Standing Sudden Occlusion of Right Popliteal Artery after an Attaci oj Endocarditis 1pparent Improre ment and Attempt at Collateral Circulation for Tuo Days Secondary Thrombosis of Femoral Artery extending as high up as I onparts lign ment at least and occluding all the Collateral Branches Gangtom of Leg on Fourth Day Double Diaphragmatic Pleurisy and Trismus on Eleventh Day Death on Tuellth DP aged 32 In h married plasterer by trade has never had rheuma Vhen 16 years old he was told boy hot phy ician that he had tism ·25 DEATH AND DISABILITY FROM SYSTEMIC ARTERIAL EMBOLISM Ilth heart disea e the character of much has not stated and was adsı ed to Bne up hard work and aroid excitement August 6 1873-as first called in ee this patient and found his stomach largely distended with ga bonels open har tympanulic pule 150 irregular and intermittent (mesenteric emboli m auricular fibrillation') Questions and parenthe es pre ent author] 7th Morning Examination of heart revealed hypertrophy of leit ventricle with dilatation and some valvular disea e of the eract nature of which I could not be certain on account of the rapid and integular action of the organi 8th.--Extreme soliering from dyspnora during pa t night no oedema of lower extremties at any ime at half ra i one whule walking acro s the floor he had experi enced a ens p of numbnes in the right leg remarking that he had no control over it. This was followed almost immediately by exceedingly acure pain in the muscles of the call compelling lsm to lie dowa De Cole at once dsrected the limb to be bothed in hot mustard rrales and ugorously rubbed Italics pre ent author s ) The mu cley were perfeculy Naccid the on was wlute as marble and apparently as bloodles and the surface from a hands breadth above the knee to the extremity of Iberoes perfectly cold Pulsation could be felt both tibials of the left limba saglit side no pulsation could be felt below the opening in the adductor magnu for the passage of the lem sral The patients general condirion was indica one of arute suffering this head and upper extremurer mere bathed in Perspirenon and he tossed about the bed racetan ly begging some on to shoot him to put him out of his pain Italis ose pst 11 author 8 ) Tbe dia no is was made of embols m of the right popliteal attery liya clot or vegetation from the salyes of the bear On the 23rd day at 2 o clock A V he died perfectly quietly imposible to obtain perm son to make any po t mortem examinalı it was Whatever-a circum tance much segretted Ward reſers to another patient auth emboli m to the popliteal artery who was in perfect agopy In addition to yeast poultres externally the internal treatment uas supporting and stimulating (italics present authors) the patient s daily allowance being four pounds of fresh lean beef made into a trong brath three eggs and a sufficient quantity of milk made into punch and « ! mulanes one quart bottle oj brandy one halj plat of sherry and one pint of champagne-the later to con trol nausea (Again present authors italics ) The patient also fre quently took as much as four ances of laudanum in the st hours to Telseye pain The modern dosage of alexbol recommend d for periph eral asodilatation would appear of relatiely homeopathic amounts in ·26 SYSTEMIC ARTERIAL EMBOLISM supportive, stimulative, and antınauseating effect Ward found only one recovery in 30 published cases of embolism to the extremities It may seem gratuitous to recall at length the errors of the pat, but even today, with modern methods, the treatment of any single embolic episode is one of frustration inasmuch as only the effect ſembolism) rather than the cause (cardiac mural thrombosis) is being treated The most frequent type, cerebral embolism is at present inaccessible to embolectomy, and has a high mortality rate Emboli lodge in acces sible site in relatively small proportion, and despite the most skillful medical or surgical treatment results are often unsatisfactory Recovery assures no immunity against an early serious or fatal recurrence flox great the danger of recurrence may be, we must consider next MORTALITY IN SURVIVORS OF ARTERIAL EMBOLISM Duration of Survival Period after Recognized Embolism Recovery from the first attack of embolism in no way terminates the danger of future emboliem but actually increa es at Any optimism generated by the survival of an occasional patient for many years without treatment is dampened by an examination of the usual natural history The subsequent natural history in sistemic arterial embolism is that of short urval and a lugh proportion of deaths are due to recurrence Whether the initial embolus is removed or the condition treated expectantly survival is about equally long The danger is well illustrated by Strombeck s " follow up on the 60 "successful cases of survial following embolectomy for all causes in a group of 327 treated in Sweden (1912 through 1932) A fourth of the patients were dead within a year of operation half of them in three years and two thirds in five years femiplegia cau ed 12 of the 41 deaths and occurred in 4 of the 19 survivors Strombeck 19 observed that since these were heart di case patients who had already been exposed to arterial emboli it seems reasonable to assume that a large number of these hemiplegias and perhaps most of them were due to cerebral emboli Since the sources of embolism were all types of heart disease the e figures reflect a general prognosis as to the length of surunkal following embolism

·11
DEATH AND DISABILITY FROM SYSTEMIC ARTERIAL EMBOLISM
RECURRENT EMBOLISM AS CAUSE OF DEATH
la sy tetnic arterial embolin etting on in patients with thru
matic beart ducare recurrence is sunularly frequent and urinal al o
bort. Ang & 39 such patients 32 survived for an aferage of only
three and one half years according to Bigalow and Greenwood who
EMBOLIC DEATHS
14
CARDIAC DEATHS
12
NON CARDIAC DEATHS
10
- NO OF DEATHS
8
9
2 4 5 6 7
10 11 12
YEARS
FG Graph showing face of 52 DSvisors of sy temic arterial emboli na
(Type of death
did not specify the causes of death In another group of 52 27 died
within 3 years 14 from recurrence 56 (704Rocurrenres were enthu
frequent and serious
One mar approtunate the danger of death from eml olism in theu
matic heart disea e as follows DE 20 patients with recognized embo
Iism about 10 dve up the fs a lack and about 38 (45 per cent) of
the Rurynin, 8 dip of recurrent emboli m Thus the risk of death
from embolism) ja the first or subsequent attacks as orer 50 per cent

·28 SYSTEMIC ARTERIAL EMBOLISM The Period of Greatest Risk of Recurrent Embolism The period of greatest likelihood of recurrent emboli m in rlieumatic heart disease in the study of Daley ct al 6+ was immedintely after the first recognized episode In 115 patients who had multiple cpi odes about as many had recurrences within a sech (32) as did in the next three weeks (41), and as many in the first month (73) as in the next 43 41 40- 38 32 33 30- 20- NO OF EPISODES 12 - O wwwwww I DAY TO I WEEK TO I MONTH 6 MONTHS I YR. TO 5 YEARS OVER 10 1 WEEK MONTH TO 6 MOS. TO I YR 5 YEARS TO IO YRS YEARS INTERVAL Fig 5 The time interval between recurrent emlolic ep odes eleven months (71) sec FIGURF 5 Of 201 recurrent episodes within ten years, 144 (or 71 per cent) occurred in the fir t year The danger continued however not just for a short period after the fir t embolısm but throughout life About luulf the deaths early or late were due to systemic arterial embols m moreover it could be said of the survivor at almost any time after the initial episode that half of them cientually would die of systemic arterial embolism The danger became progre sui cly less imminent but was ultunately no less certain The chance of recurrence of systemie arterial embolism in rheumatic heart diserce is thus many times greater than the chance of a primary episode Once the essential tlırombus has formed in the left auricle and ·29 DEATH AND DISABILITY FROM SYSTEMIC ARTERIAL EMBOLISM has been mobilized a continuing substrate for recurrent embolı m exi ts Until the underlying mechanım which produced the primary embolism is altered there is no reason to s ume recurrent embolim will not be the rule The evidence indicates that onre emboli mn begins it continues in one patient reported by Vright nine emboli oscutred within ten day Although recurrent arterial emboli has not been well tudied it heart disea e of nonrheumatic origin and would seem clinically to be le s common certain studies indicate frequent embol o arieing from Frantricular mural throhibi Towbans 48 report of recurrent cerebral emboli m from fragmenting left sentricular thrombi is an excellent chiniral prototype Thrombı may per it over a healed myocardial farct and account for repeated minor unrecomized arsenal occlu4on REPEATED EMBOLECTOMY At tives the recurrent embalı lodge repeatedly in aite acceable los removal so that repeated embolectomies are necessary Although the ame astery may be occluded recurrences are more frequently at differ In seg Beforr adequate antithrombolic mea ures were asaslable to inhubst rau atue cardsac mural thrombo 13 recurrent emboli m Tequired re poated embolectom--on occasions a disheartening experience in 1939 Dicomarol was not in use and although heparin was available 29 necessary to ne it by injection and the need for a prolonged unin terrupted antithrombotic action was not appreciated MacFarlarıms ra c 29 eloquenti Cose Report An unmarried woman uge 27 was admitted to be bepaal prs! 12 1939 with a diagnosis of acute appendicitis Exampinalinn af the heart revealed igns of mitral tenosis with auricular fibrillation and a ventreulat rate of 170 D spite the abdominal pain Forriting and tender ses in the right flac fossa sh te was no 1)idity the leukocyte count Kds 18 200 It was the fr that she might have a mall embolic me enteric Relu 1on sono operate is wa performed on April 17 five days later he complained of a numb feclmg in the left leg and harp Pain Palls deselnped ard the pul could not be sehr below the common famosa) artesy An embolo nas found riding on the bifurcation of the common femoral artery and was remosed (first embolectomy) Heparin slutna was given for eight days and then discontinued The following day April 26 numbne za she right foof developed The font became cold and cyanosed Pul atun was ah ent delow the right lemoral artery A large erbolus wa ·28 SYSTEMIC ARTERIAL EMBOLISM The Period of Greatest Risk of Recurrent Embolism The period of greatest likelihood of recurrent embolism in theunalıc heart disease in the study of Daley et al ' was immediately after the first recognized episode In 115 patients who had multiple episode about as many had recurrences within a week (32) as did in the next three weeks (41) and as many in the first month (73) as in the next 50 43 41 40- 38 32 33 30 NO OF EPISODES 12 을 wwww 1 DAY TO WEEK TO I MONTH 6 MONTHS I YR TO 5 YEARS OVER 10 I WEEK 1 MONTH TO 6 MOS TO YR 5 YEARS TO 10 YRS YEARS INTERVAL Fic 5 The time interval between recurrent embolic emode eleven months (71) cee FIGURE 5 Of 201 recurrent episodes with ten years 141 (or 71 per cent) occurred in the first year The danger continued however not just for a short period after the fir t embolism but throughout life About half the deaths early or late were due to systemic arterial embolism moreover it could be said of the survivor at almost any time after the initial epi ode that half of them eventually would die of systemic arterial embolism The danger became progre sively le-s imminent, but was ultunately no less certain The chance of recurrence of systemic arterial emboli m in rheumatic heart disease is thus many times greater than the chance of a primary episode Once the essential thrombus has formed in the left auricle and ·DEATH AND DISABILITY FROM SYSTEMIC ARTERIAL EMBOLISM on 66 obtained a ki tory of previous major embolc eps ades for 6 of 13 patients with aortic embolism In a study of sy ternic arterial embolism in patients with theumatic heart disea e Daler i found that more than two third of hp 73355 of the fir t recognized attack (115 of 171) had at lea t one recurrenten some as many as 18-manst attacks being within ix months of each other Among Co griffs: 35 patients with recurrent emholim only four had had a single previous epi ode Recurrence 18 8 well e ral) hrd rule, therefore and the pattern of recurrence « 29 certain Irom one recognized embolism as from two There « actually greater probabilis that a patent with one episode will have a second than shal a patient with two will have a third Finally however probable as recurrence may be the servou neus olan future episode is unpredictable Anı ca e may eventually and the inat reported by Teplick and Yarron 21 whose patent will reumatic mitral valve decea and auricular fibrilation recos cred from embol u in the renal artery but dued uddenly within three months aimilar Cores described by Linton? whose patient recovered from embol in in an extremity only to die twelve days later from cerebral embol m The burden of proof would seem to be on those who believe that single ept odes of embolism prcur There is little pathologic proof for this belie? 13. In necropsy studies angle isolated infarcis are the exception the usual finding being multiple infarcts which are frequently of different ages evidence that the base bees fjerted not in a single shower but poradıcalls throughout the patient a lıfe 137 17 Among 189 patients studied at nerropay Bull 47 found 301 emboli in the 15 palients with embolim in the extremities there were 30 embols in other stes besides insolung an hut one of the fiftern Ile rather foscelully adjured in g ney' it is important not to tarp blindly at the extremital embolism, but to remember clearly that the tatter 13 most often noth ng less ban a link in a chain of emboh in other organs prior th sultaneous with or sub equent to extremital embnim The period of potential emesluzation in themanic heart di ease and thus the dange of disability and death is a continuous one from the time of the first emboli m slal death Mort of the minor embolisms which forekara of the ub equent major emboh m clinically unrecoguzed. arc ·30 SYSTEMIC ARTERIAL EMBOLISM removed and heparin again was given intravenously (second embolectomy) On May 3 seven days later heparin was discontinued The following day May 4 she had sudden lower abdominal pain sacral cramp pain down both thighs and showed some shock No pulsation was felt below the bifurcation of the aorta Doctor MacFarlane said it was with considerable misgiving and a feeling of discouragement that further operative treatment was contemplated A large embolus was found at the bifurcation of the aorta but it was difficult to prevent a portion of the embolus from alıpping away The major portion was removed (third embolectomy) lleparin na given continuously again Three days later on May 7 she developed all the signs of another embolus in the right femoral artery! One began 10 wonder whether the whole thing was futile but after further serious con sideration a good sized clot was removed (fourth embolectomy) The clot was located at the right femoral bifurcation Doctor MacFarlane felt that a small piece had escaped into the femoral artery Heparin was con tinued until May 28 Nine days later on June 6 she had right facial weakness paralysis of the right side of the tongue and a cold blue left arm These findings di appeared foxeser tlie following day She rapidly regained her strength and was sent home on June 28th This patient's repeated major arterial embolism (sıx episodes within two months) which occurred after di continuance of heparin and re quired four embolectomies illustrates the danger of rapid recurrence and the necessity of continuous control of coagulability during the period of acute thromboembolism Gilfillan and Freeman 89 in a personal communication record an carly case of a 61 year old woman with rheumatic mitral stenosis and auricular fibrillation Following embolism to the abdominal aortic bifurcation for which embolectomy was done regional heparınızation was induced The venous blood in the arms and presumably the blood in the left aurcle however was normally coagulable Three days later a second embolism occurred again to the bifurcation of the aorta and embolcctomy was again performed The next day death occurred fol lowing cerebral embolism At necrops, the left auricle was found to bc dilated the mitral orifice admitted only the little finger and an unattached laminated thrombus 2 cm in duameter was found in the left auricular appendage ( ee frontispiece) Patients with embolism usually give histories suggestive of previous attacks says Lund 159 In 228 patients with sarious heart diseases Haimovici found 443 resulting embolTwo embolic episodes per patient was the average reported by Des Prez and lubas En for 28 patient with acute arterial embolisin due to rheumatic heart disease Wilkin ·3 Clinical Correlations of Cardiac Mural Thrombosis and Systemic Arterial Embolism Rheumatic Heart Disease SYSTEMIC ARTERIAL, EXIBOLISY in theumatic heart direa e occurs in a certain group of patient Clinicians long have recognized that left auricular thrombo is and systemic arterial emboli m are more frequent in those patients with longstanding mytral strno is auricular fibrillation and congestive heart failure that is others with theumatic heart di ease without these complications The primary correlation of such thromboembol mi mut be with the formation of left auricular thrombs In a composite group of 899 patient unclassified as to thithin or type of valvular Ip ron studied at Decropsy 216 (26 per cent) had left aurular thrombosis (TABLE 6) Thus complication can be correlated fałışlıcally with both miiral cenosis and auricular fibrillation but contrary to the general impre sion not with congestive heart failure that is not with clinical failure of the nght side of the heart Auricular Fibrillation and Right Heart Failure in Rheumatic Mitral Stenosis The time relation hetween the onset of auricular fibrillation and the development of right heart failure in mitral stenosis 14 important TABLE 6-Inndence of Thromb in the Left Aundle (Body or Appendare) in a Composte Croup of 899 Parents Dreng of Chronic Rheumatic fee Drease Author number of patient Number of lest auricular thrombi Per cent Soder Trom 19 29 101 (taban el al Wallaclı et al 33 509 123 24 Total 829 216 26 33 ·32 SYSTEMIC ARTERIAL EMBOLISM SUMMARY Probably 25 to 30 per cent of deaths and an inestimable amount of disability in rheumatic heart disease result from the formation and ejec tion of left auricular thrombı as systemic arterial emboh In the natural course of this disease process about one in six of those with emboli m die of the first episode and about half the survivors are dead within three years, nearly half of these because of recurrent embolism The danger of death in the first attack in rheumatic heart disease is not nearly as great as is the danger of death from recurring emboli m About 10 per cent of deaths in acute myocardial infarction can bu ascribed to systemic arterial embolism in healed myocardial infarction and arteriosclerotic heart disease with hypertension, the death rate is less About one fourth die in the first attack Recurrent emboli m as a caume of death in arteriosclerotic heart disease occurs but it is not as well documented Embolectomy irrespective of the cause of the embolism, at times is an urgent life caung procedure but it is applica ble to only a small proportion of patients Next to the coronary arteris (which are rarely involved) the cerebral arteries are the most dan gerous sites for embolism Cerebral embolism is the most frequent, and at present is inaccessible for embolectomy The survivor of an emboliu episode whether he survives through con crvative treatment or through surgical removal of an occluding thrombus faces the same danger of recurrence The number of embolisme identified during life is small in comparison to the multiple disseminated embolic infarctions revealed at necrops) ·CLINICAL CORRELATIONS 35 cally diagnosed sy temic arterial emboli m in rheumatı heart disease (TABLE 7) the frequency of this occurrence in those without congen tre failure indicates that the thrombı y vally form before the on et of congestive lažlure TABLE 7.--Congestue Failure in a Composite Group of Patients wuh Rheumate Heart Disease and Clinically Recogni ed Systemic Arterial Embolism (Presumpte Endence of Left Auricular Thrombosis) Number with embolim Number Per cent without without congestive congestive failure failure tuthor Comments Terss and Davis 26 (Fatal) 17 65 Bourrie 29 21 83 Harris and Levine 49 72 (Cerebral) 68 17 had "slight or no evidence of conges trie failure 24 had goud exetce tolerance Dormally ambulatory" 49 without Wales en orged laseror edema 69 had congestive fail ure 41 mild 4"mod erate "Uual clinical standard." "Right heart failure" Daley et al 123 61 194 15 clinical ecognition) Ole en 75 49 66 in 26 Belcher and Somerville St 78 listory of congestive failure in 1z* Total 450 306 68 Harris and Levine, 16+ in a study of 72 cases of cerebral embolim in nitral tenosis found this complication more likely to occur in tho e with very little objecure evidence of congestie failure Bovine 31 reported that of 29 suullar instances 24 occurred in patients with good exercise tolerance who were normally ambulatory Facquet Hus on, and Ducrot state that contrary to pulmonary emboh which practically alwais orcur in the bedrudden subjects, the peripheral arterial emboli ·34 SYSTEMIC ARTERIAL EMBOLISM Auricular fibrillation frequently if not usually, precedes rather than follows right heart failure and in a large proportion right heart failure is a late, not an early subsequent des elopment Olesen 179 studied 206 patients #ith mitral stenosis and auricular fibrillation (148 females and 58 males) for a period of from 3 to 20 years Although 82 (40 per cent) had right heart failure when the arrhythmia uas fir t diagnosed in 73 of these, both right heart failure and auricular fibrillation were present when first scen, and no reliable history either as to priority or to time relationship was obtainable But in the 133 patients in whom the time relation could be determined auricular fibrillation occurred first in 124 and right heart failure firat in only nine case Furthermore in thene patients in whom the arrhythmia appeared first there was a long period of auricular fibrillation before right heart failure developed In only 27 of the 124 such patients did right heart failure des elop within five years Eighty per cent, therefore went five years without development of right heart failure Olesen 173 said that the "development the complete heart failure described from the three stigmata heart size heart rhythm and right heart failure, generally occurs in such a way that the heart first increases in size then auricular fibrillation des elops and this is followed at lat by right heart failure? Enlargement of the right ventricle occurs after the left auricle has failed The time sequence in the cardiodynamics of mitral stenosis would appear to be first left auricular dilatation and failure eventually auricular fibrillation and last right heart failure The long survival period of the entire group of 206 patients with auricular fibrillation is instructive Fifty per cent of the females sur vived six to seven years and 50 per cent of the males survived four to five years This emphasizes the need for a long period of observation in evaluating prognosis as to survival and for the inclusion of the tho e cunning as well as the deaths The older concept that those with auricular fibrillation died within three and one half years after its recognition is true only in groups observed for a relatnıely short period of time Congestive Heart Failure and Left Auricular Thrombi Diagno ed by the usual criteria-peripheral venous engorgement and edema--congestive heart failure is not present in the majority of living patients presumed to have left auricular thromb. The pre-umpire diagnosis of left auricular thrombosis is based on an episode of clim ·37 CLINICAL CORRELATIONS auricular thrombı were present in 4 per cent of patients with pure tenosis in 18 4 per rent of those with predominant <tena and less than 10 cc regurgitation and an only 9 1 per cent wah pure insufficiency --regurgitation exceeding 10 ce The findings of Janton et al ' in 200 patients were almo t identical Thus e definite correlation of left auncular thrombosis relik metra! slenost u evident Nearly all patients with left auricular thrombo is have predominating mistral tenosis and 44 per cent of tho ro with pure mitral steno is have left auricular thrombosis Auricular Fibrillation and Left Auricular Thrombosis The correlation betnéen auricular fibrillation and left auricular thrombosis may be tudied in a similar way By the incidence of fibril laron in thrombosis diagnosed during life or at necropsy, and conversely by the incidence of thrombi in persons with fibrillation About four TABLE 8 RELATION OF RHYTHY TO LEFT ALNICLLAR TIROTEOSTS Percentage of Aurirulas Fibrilation in Pansen's wath Rheanaic Heart Disease and Clinically Diagnosed Systemic Anterul Embolism Il resumpitte Eridence of Lt Auricular Thrombosis) Patients with rheumatic heart di ea e and sy lemi arterial eccluson Isticats with auricular fibrillation L'escentage with auricular fibrallax Author llam ICI 92 75 81 5 Harrs and Levine 79 55 76 Dales et al 197 17 82 ck on 69 35 50 Teller and Somerville 54 42 78 Ole en 67 57 85 ( ver el al 81 68 Total 80 632 06 80 ·36 SYSTEMIC ARTERIAL EMBOLISM strike often the well person carrying on without difficulty in his habitual occupation” They point out that the heart lesson is often sa well tolerated that it is the embolism which disclo es it Daley, et al in a study of 194 cases, were unable to correlate the duration and severity of failure with either the onset of systemic arterial emboli m or the number of emboli It is obvious that one must suspect embolism before the onset of congestive failure Mitral Stenosis and Left Auricular Thrombi The clinicians concept regarding a significant association of left auricular thrombosis with mitral stenosis is readily borne out by studies based both on clinical diagnoses and operative findings Nearly all left auricular thrombı are found in patients with predominant mitral stenosis and conversely a high proportion of tho e sith mitral stenosis have left auricular thrombi A correlation based on clinical findings however is only presumptive Cimical diagnoses are not accurate for either left auricular thrombosis or mitral steno 14 Lelt auricular thrombı can be diagnosed only presumptively of based on the clinical recognition of systemic arterial embolism The clinical diagnosis of the degree of valvular stenosis and regurgitation is notori ously unrehable Based on clinical evidence therefore one can only state that presumptive thrombosis appears nearly always in patients with presumptive mitral stenosis In Daley su* 194 cases of syatenuic arterial embolism, mitral regurgitation predominated in only three The only accurate diagnoses either of left auricular thrombosis or of a valve lesion are those made during life at operation Only since cardiotomy permitting digital exploration of the left auricle has accurate diagnosis been possible either of the anatomic type and degree of valvular deformity or of the functional predominance in flow of stenosis or regurgitation But more important for the first time the simultaneous presence of three conditions can accurately be determined and correlated (1) left auricular thrombosis (2) the functional vak ular lesion and (3) auricular fibrillation Of great value have been the studies of Storer et al 36 who learned to estimate the degree of regurgitation by immersing a finger in 1 beaker of water and directing a jet of measured volume against it with a syringe They classified regurgitation roughly as either more or les than 10 cc per systole In 225 cirdiotomies it was determined that left ·39 CLINICAL CORRELATIONS hereier left auncular thrombi are encountered on theumarıc Hear! disease therefore--whether dunng hfe as diagnosed by clinical arterial embolism during cardiotomy or after death at necropsy-80 per cent are associated with auncular fibrillation Conrer ely about half of the patients with auricular fibrillation have left auricular thrombouis 2232 (TABLE 10) The chance of a patient uith rheumatic heart disease and auricular fibrillation having a lele cunicular skrombus is about four times that of a patient truth normal sinus rhythm Mitral Stenosis versus Auricular Fibrillation It 18 evident that leit auricular thrombosis cas be correlated with both auricular fibrillation and pure mitral teno 15 Forty four per cent of the patsents with pure mitral feno 13 in 225 cardiolomes had left PER CENT 90 80- NORMAL SINUS RHYTHM FIBRILLATION TO NORMAL SINUS RHYTHM 3 FIBRILLATION 74 6% FIBRILLATION 20 51% NORMAL SINUS RHYTHM 40 30 20- 25 47 GROUP Y GROUP IT GROUP TTT FIG 6 lacidence of auricular ábrillation and normal thythm in 225 patients wbo had operation for matral raleglas disease froup 1 "pure Tastral stenosis Croup 1 outral stenosis plus regurgitation Group 1] pure miral insuficiency (Figures 6 and 7 reproduced by permi sion from Storer S et al Physiopathological corcepts of mitral valvular de ea e A1 Klay 8 1941 ·38 SYSTEMIC ARTERIAL EMBOLISM TABLF 9-Percentage of Auricular Fibrillation in Patients Dying of Rheumatic Heart Disease uuth Left Auricular Thrombi (Alecropsy) Author Patients with left auricular thrombi Mumber with auricular fibrillation Percentage Soderstrom 60 46 76 Jordan et al 50 42 844 Weiss and Davis 25 22 88 Graef et al 14 10 71 (raham et al 33 30 90 9 Total 182 150 82 fifths of those with left auricular thrombi hava auricular fibrillation and converscly about half of those with auricular fibrillation have left auricular thrombi Among a total of 440 patients with thrombı found at cardiotomy compiled from five reports the incidence of auricular fibrillation was 86 per cent 14 131 1 91 0 Auricular fibrillation av also present in approximately the same proporlion—80 per cent of 632 cascy--of those with pre umptive evidence of left auricular throm boars those in whom systemic arterial embolism nas clinically diag nosed (TABLE 8) Further corroboration comes from necropsy (TABLE 9) at which left auricular thrombı were found Again the incidenci of auricular fibrillation for this group is d2 per cent TABLE 10 RELATION OF RHYTUN TO LEFT AURICI LAR TIROPOSTS Incidence of Left Auricular Thrombi at lecropsy in Patients uuh Rheumatic Heart Disease (Normal Rhythm tersus Anricular Fibrillation) * Percentage Mumber Number with left Rhythm of patients auricular thrombi Normal 150 Auricular fibrillation 170 76 Total 320 93 * From compiled data of Soderstrom and Graham et al 11 44 29 ·CLINICAL CORRELATIONS thrombosis (3 per cent) The addition of auricular fibrillation as a factor cau ed an abrupt rise from 3 to 81 per cent. Thus although about half of all patients with auricular fibrillation without respect to the vale lesion had left auricular thrombi oser three fourths of the e with auricular fibrillation plus pure mitral stenosis had left auricular tiramo) $ Here the caution of Pearl 191 my t be remembered Furt lat and all the time that an ob ensed correlation measures nothing and means nothing but a statistical a sociabon not caucanon Aurtcular fibrillation appears to have clinical importance chieſls as an index of a composite group of factors strongly predispo ed to throm be us The correlation belkeen auricular fibrillation and leit auricular thrombosis is the mo tarcurate we have It is certainly the most helpful to the clinesan of the two correlating factors (auricular fibrillation and mutral stenosis) only the arrhythmia can be diagno ed accurately and identities the group who have 80 per cent of the sy !rmic arterial embolism Estimating Danger of Systemic Arterial Embolism The danger from systeme arterial embolism for any person can only he e tunated ince it is based on the likelihood of three po abilities first that left auricular thrombi exit second that they will be mobilized as embols and third kon the lodgment of the embolus wall re ult-harmle ly of in paraly«19 gangrene or sudden death. The Chance of Left Auricular Thrombosis In those with no bi tosy of systemie artersal embol m the chance of left auricular thrombosis can be estimated from the rhythms and from the type of mitral salvular lesion With normał rhythm the chance a about one in ters excluding pure mitral regurgitation With auricular fibrillation houses the type of associated mitral salvular lesion deter mines the charce of a left auricular thrombus In puse mytral stenosi leit aur ular thromboss ocf273 in about three fourths of those with auricular fibrillation while pure mitral regurgitation Tedures the chance 11 auricular bbrillation to about 10 per cent (FIG 7) The need for accurate diagnosis of the degree of teno is and regur mation remains a challenge to the clinician The average clinical diag Hoc error in all three grouppure stenosis pure regurgitation and the mized conditias--s still fugh but probably will be leadily reduced (TABLE II) Bjork demonstrated how she left auricle can be cathe ·40 SYSTEMIC ARTERIAL EMBOLISM auricular thrombosis, whereis 53 1 per cent of the patients with auric ular fibrillation in the same group had left auricular thrombosis Although pure mitral stenosis identifies the group in which H per cent have left yuricular thrombı, the importance of auricular fibrilla tion is shown when the incidence of those with arrhythmia is compared 100 FIBRILLATION 90 80 84% 70- 60/ 50 FIBRILLATION 40- 30- NORMAL, SINUS RHYTHM NORMAL SINUS RHYTHM 36.1% NORMAL SINUS RHYTHM FIBRILLATION 20- 10 919% B1% 0% GROUPI GROUP I GROUP DI FIG 7 Incidence of left auricular thrombi in those with auricular fibrillation and normal rhythm in the three group Croup I steno is Group II mitral stenosis plus regurgitation Group III pure mitral regurgitation pure mitral with those of normal rhythm Storer Lisan Delmonico and Bailey }} reported that among their patients with pure mutral stenosis there were about as many with quricular fibrillation as with normal rhythm- 51 to 49 per cent (FIG 6) But among those with fibrillation 81 per cent had left auricular thromb: while among those with normal rhythm there werc thrombi in only 3 per cent (FIG 7) Thus although mitral stenosis apparently was essential as a subtrite factor for ielt auricular thrombosis, it was by itself 1 relatively negligible factor in inducing ·CLINICAL CORRELATIONS without overt embolism and without regard to the type of mitral valvular lesion about 10 per cent (3) in tho e with auricular fibrilla tion and pure mitral tend is nearly 20 per cent and (4) in those surviving clinically recognized emboliem regardless of the associated rhythm about 45 per cent (la tho e with clinically recognized syetemic TABLE 12-Estimated Chance of Left Auncular Thrombosis obili allon of Thrombt and Death From Eventual Embolism in Rheumaric Heart Disease Estimated chance of left muncular thrombos19 Fstimated Tercentile chance of death Iroent Mentual emliliam Estimated chance of mobiluation Group 100 Patients 1 10 5 2 With normal rhythm ini teronizedem bolism) With aunstplas fibri) lation (no reco Dized embolism) with out regard to valve 50 25 ܐܐ le con 3 81 42 19 With auricular fibri fation and pure" utsal stenosis (10 recognized embolism) With recognized sys temic arterial embo 1 m (80 ser cent have suscular fibrillation 4 100 100 45 arterial emboli m the presence of imminence of formation of left autxular thrombi will be postulated Although the individual percenisle Tik is necessarily approximale the order of arrangement in the order of lik is logical In addition in the nk of death serious disabilities are suffered by a small proportion of the survivors Although the ill of loilm may be thus tou hly graded and the greater nk recognized in the patient with pure mural stenosis and av xwar Abtulate the cut ·42 SYSTEMIC ARTERIAL EMBOLISM terized through a needle introduced into the right paravertebral space and the degree of regurgitation determined He considered this the method of choice Others have used this method and are impressed with its accurate correlation with the findings at operation 135 74 53 Although the sequelae usually are minor, deaths have occurred follon the procedure, in addition to pneumothorax, hemothorax, and cardiac tamponade 39 178 "+ Transthoracic catheterization of the left ing TADLF 11-Aterage Diagnostic Error Mlade in 225 Patients by Four Groups of Cardiologists * Group 1 (Pure mitral stenosis) Group 2 (Predominant stenosis minimal unsufficiency) Cardiologists Group A Group 3 ( Pure insufficiency) 700 2504 34 6% Group B 27 57 1 27 Group C 35 41 6 63 Group D 24 18 7 100 65 Average error 27 75 38 0 • From Storer et al JAVA 155 103 1951 by permi sion auricle will probably be u ed however more and more in the pre operative evaluation of rheumatic mitral al ular disease This knowl edge will sharpen the accuracy of the prediction of left auricular thrombosis The actual danger of embolism depends of course on the mobilizing tendency of the thrombı This is estimated at 50 per cent for all tho e with left auricular thrombi (CHAPTER 2 TABLE 5) Although emboli may be minor and unrecognized at first the evidence indicates that if thrombı are being mobilized a recognizable arterial embolt m eventually occurs With this occurrence the risk of death and disability from further embolism increases abruptly By the foregoing criteria the rhythm and the type of mitral valvular lesion the approximate statistical risk of death from sy temic arterial embolism increases through four groups (TABLF 12) (1) in those with normal rhythm before recognized embolism the rik of death is less than 5 per cent (2) in those with auricular fibrillation ie ·45 CLINICAL CORRELATIONS than 40 gm there nere only 52 patients with left sentricular throm bo vs (22 per cent) but among the 87 patients with larger inlarctions there were 56 (65 per cent) Thrombosis was more frequent following infarctions of the anterior wall of the left ventricle-in 48 of 115 patients (42 per cent) Among 52 with acute infarctions of the posterior wall there were only 11 instances of ventncular thrombosis (21 per cent) ongesurse failure was mot frequent in patients who e myocardial infarction was healed but who had ventry ular thromb (70 per cent) It was less frequent in patients with both acute infarction and ventricular thrombi (48 per cent) and leat frequent in those wuhous ventricular thrombı regardless of the state of mfaiction Weight Marple and Beck 78 reporting on a study of 1031 cases of myocardial infarction stated that persi tent heart failure predi posed to thromboembole phe nomena and that such failure in a sociation with a large infarct nas e pecially favorable to formation of mural thrombi with conscquent increa e in the risk of emboliem In e timating the probabılıty of left ventricular thrombo is there fore one mu e determine as far as possible whether there is a myocardia! infarction where it is how old it is and how large it is recognizing that the probability is greater of conge tuse failure is also present One other factor was emphasized by Schlichter Hellerstein and hatz 18 Where myocardial infarction was asociated with cardiac aneury m they found that 57 per cent of their 102 patients had en tricular mural thrombo is in a control group of 410 patients with myo cardial infarction without cardiac aneurysm ventricular mural throm bo is was present in only 21 per cent They did not study the relation of congestae failure but among the wa with mural thrombi they ob seni ed embolic phenomena in 30 (61 per cent) The important clinical inlerenres are obvious The danger of sy temir arterial emboli m in rheumatic heart disease is as great before as after th adient of cone tive failure The adient of congestive faslure in creases predominantly the danger of peripheral venous thrombosis and of pulmonary embolism The important prognostic indexes of potential Y temc arterial emboli m are mitral stenosis and auricular fibrillation In arleriosclerotic heart di pase honever conge tive heart failure deſ nitely increases the incidence of left ventricular mural thrombosis and con equently the danger of systemic arterial embolt m The pre ence ol auricular fibrillation actually has no prognostie value so far as ·14 SYSTEMIC ARTERIAL EMBOLISM are useful chiefly as a clinical guide Embolism occurring in a patient with normal rhythm is just as damaging as that occurring in a patient with auricular fibrillation irrespective of the fact that the original chance of developing it was only one fourth as great Every patient with rheumatic heart disease must be considered to be in danger of systemic arterial ernbolism Clinical Correlations of Left Ventricular Thrombi Whereas left auricular thrombosis in rheumatic heart di ea e i correlated largely with the presence of auricular fibrillation and the degree of stenosis of the mitral salve and less with a demonstrable lesion of the auricular wall or congestive heart failure the formation of thrombı in the left ventricle is largely determined by the character location and size of the necrotic lesion in the ventricular wall and by the presence of congestive failure Nearly all left ventricular thromlu occur in association with coronary arterial disease or hyperten ile cardiovascular disease Auricular fibrillation is not associated with left ventricular thrombı any more than is normal rhythm This is illu trated by Jordan's 13 studies in a series of 327 patients who died either with acute or healed myocardial infarction 33 per cent had left ventricular thrombı Twenty seven of the 327 patients had auricular fibrillation but only six of the 27 (22 per cent) had thrombi in the left ventricle In Garvin s 85 study of cardiac mural thrombi there wa no correlation of auricular fibrillation with any cavitary thrombı except those in the left auricle The character of the aortic valve apparently has no significant effect on left ventricular thrombosis Aortic stenosis associated with acute myocardial infarction does not significantly increase the incidence of Jeft ventricular thrombı kumpfe and Bean 145 found four instances of mural thrombı among 13 patients with aortic stenosis complicating 1 recent myocardial infarction (30 per cent) This is an average incidence Character Location and Size of the Ventricular Wall Lesion In a necrops; study of 327 cases of myocardial infarction Jordan et al 13 correlated the incidence of left ventricular thrombi with infare tion in several ways Whereas thrombi were present in 80 of 210 patients with acute infarction (38 per cent) they were found in only 28 of 117 whose infarctions had healed (24 per cent) Another correlation was the size of the lesion Among the 240 with infarctions no greater ·CLINICAL CORRELATIONS than 40 q cm there were only 52 pahents with left ventricular throm bo is (22 per cent), but among the 87 patients with larger infarction there were 56 (65 per cent) Thrombosis was more frequent following infarctions of the anterior all of the left ventricle-in 48 of 115 patients (42 per cent) Among 52 with acute infarctions of the po terior wall there were only !! instances of ventricular thrombosis (21 per cent) Congestire failure was mot frequent in patients who e myocardial infarction was healed but who had ventricular thrombi (70 per cent) it was less frequent in pahents with both acute infarction and ventricular thrombu (48 per cent) and lea t frequent in those without sentricular from£, regardless of the state of infarction Wright, Marple and Beck reporting on a study of 1031 cases of myocardial infarction stated that per a tent heart failure pred. po-ed to thromboembolic phe nomena and that such failure in as oration with a large infarct was e pecially favorable to formation of mural thrombt with consequent tricrease in the ri k of embol m In estimating the probability of left ventricular thrombosis there fore one mu i determine as far as posible whether there is a myocardial Infarction * re it is how old it 19 and how large s 15-serognizing that the probability is greater of conge tive failure is al o present One other factor was emphasized by Schlichter llellerstein and hatz! Where myocardial infarction has a ociated with cardiac aneury m they found that of per cent of their 102 patients had en frxular mural thrombo is in a control group of 410 patients with my cardral ıníarction without cardiac aneurysin ventricular mural throm bo 19 was present in only 21 per cent They did not tudy the relation of conte tive failure but among the 50 kith mural thromb they at served embolic phenomena in 32 161 per cent) The important clinical inferences are obtious The danger of systemic arterial emboly m in theumatic hes!d spa e ss as girar before ay after the advent of congestive fazlure The adient of congestie failure in creasas predominanty the danger of peripheral senops thrombosis and of pulmonary embolism The important prognostic indexes of potential sy temyc arterial embolism are mulral stenosis and auricular fibrillation In arteriosklerotic heart di ease however congestive heart failure deft nitely unereases the incidence of left ventricular mural thrombosis ant con equently the danger of systemic arterial emboli m The presence 01 auricular fibrillation actually has so prognostic value sa far as ·46 SYSTEMIC ARTERIAL EMBOLISM it reflects the presence of more left ventricular mural thrombl than normal rhythm, sale that frequently it is associated with congesine failurea definite thrombotic factor SUMMARY 1 Left auricular thrombosis and systemic arterial embolism in theu matic heart disease can be correlated with both mitral stenosis and auricular fibrillation 2 Auricular fibrillation is the most helpful correlate it is easil recognized and identifies 80 per cent of the patients who will have systemic arterial emboli 3 Left auricular thrombi in rheumatic heart disease in mot in stances, are unrelated to congestive failure (right heart failure) 4 The risk of death from systemic arterial embolism in any person with rheumatic heart disease depends on the chance of an exi ting left auricular thrombus and the chance of systemic arterial embolism The e chances can be estimated by a composite evaluation of three factor the heart rhythm the type of mitral valyular lesion and the pressous occurrence of embolism (TABLE 12) 5 Left ventricular mural thrombosis almost invariably occurs in nonrheumatic heart disease and over 90 per cent of the instances occur in association with coronary arterial disea e or hypertensne cardiovascular disease Left ventricular mural thrombosis can be correlated with the character of the endocardial lesion (its age size and location) Auricular fibrillation cannot be correlated with the formation of clots in the left ventricular chamber in arterio clerotic heart disease Con gestive heart failure, of little correlative significance for left auricular mural clots in rheumatic heart discase is definitely correlated with the formation of mural clots in the left ventricle in arteriosclerotic heart disease ·4 Pathogenesis of Vascular Thrombosis ALTIOLCH FOUR FIFTjI5 of the left auricular thrombt in sheumatic heart disease are found in patients with both mitral steno is and auric ular fibrillation the precise pathogenetic connection between these findings is unknown About half of those with rheumatic heart disease and auricular fibrillation have left auricular thromboeise-why we do not know nor do we know why the other half do not form Ihrombı We know much more about when and where thrombosis occury than we do about why and how it occurs The precise mechanı m of blood lorting esen in a test tube where interacting components may be assembled in a fairly constant relation hup is not known and the con fu con over such a tatic system is multiplied maniold when one at tempts to understand the intravascular clotting of blood in a dynamic $) stem For a relatively imple clinical concept of thrombo the under lying factors may be reduced to the hi torical triad of Senac and Virchou ! - the thrombotic timulus of damaged endothelium the coagulability of the blood and the degree and duration of stagnation in blood flow Regirdles of the approach to the problems of throm bosis says Jaques 1 the evidence mut clarify the mechanı ms by which these three po tulated factors operate THROMBOTIC STIMULUS OF DAMAGED ENDOTHELIUM Clinical thrombosis occurs at a site of endothelial damage damaged esther by inflammation or atherosclerotic degeneration or secondarily as a re uit of stasis of blood how 149 In arterial thramba is endothelial damage 19 usually obvious and is due either to atherosclerotic roughen Ing or to inflammatory changes in the presence of intimal toughening ta is of blood flow then increases the likelihood of thrombo 1 Thu thrombo is in the cerebral coronary mesenteric and extremital arteries occuts typu ally at an atherosclerotic site and more frequently in stasıy due to cogcentaxe failure Indeed it 35 rare to find arterial thrombo is without endence of preceding endothelial damage Occasionally hart 47 ·48 SYSTEMIC ARTERIAL EMBOLISM fer 131 says the amount of arternal damage may be a slight as not to be demonstrable morphologically The likelihood of thrombosis bears a relation to the type of endo thelial lesion Among the diseases ini olving arteries thrombosis occurs readily in thromboangnitis obliterans and thrombotic thrombocytopenic purpura, leas so in the arteritis of systemic lupus erythemato us poly arteritis and scleroderma and only rarely in rheumatic arteritis 13 *** In atherosclerotic roughening of the intima the tendency varies There is a selectivity of site not always easy to explain Platelet thrombithe so called aortic oysters --may adhere to a plaque in the ab dominal aorta even though the stream is relatively fast Conversely although Johnnon and Baggenstoss 1 8 found evidence of arterio-elerosi commonly in the mesenteric arteries it was seldom accompanied there by thrombosis except in cardiac failure STASIS OF FLOW The tendency to propagation of a thrombus after it has occluded the lumen of an artery varies with the type of artery and the type of flow The tendency of a coronary artery thrombus to propagate is not a great as in other vessels In a necropsy study of 327 hearts with myocardial infarction Miller Jordan Parker and Edwards 171 found very few thrombı more than a centimeter long Linton 157 however found rapid and extensive di tal propagation of an embolu- occludinn an artery of the extremity involving even the small tributaries of the peripheral arteries and stated A thrombus may form distal to an embolus as early as nine hours after the occurrence of the emboli in By then it may be an extensie as to prevent the return of the circu lation to the extremity Venous thrombi arise in many instances where there is stasis without any perceptible underlying endothelial daniage--for example in value pockets of peripheral veins as shown by Paterson and McLachlin in who found no lesions even microscopically As in arterial thrombo is the selection of sites is inexplicable although stasis in certain nous systems increases the likelihood of thrombosiy-es conge le failure in peripheral cerebral and prostatic veins in other systems despuite stasis thrombosis occurs rarely in the Iner although the central blood flou may be rapid congestie failure causes pa ske engorgement of the blood in the sinuses and in the mesenteric venous radicles and ·49 PATHOGENESIS OF YASCULAR THROMBOSIS increa es portal pre eure nevertheless, intrahepatic thrombo 14 14 rare under the e conditions and mesenteric venous thrombosi in con tradostinction to mesenteric arterial thrombose cannot be correlater with congestige farlure as exted frou Johnson and Baggen lo al 19 only 9 of 99 cases of mesenteric venou thrombosis collected from the necrops: files of the Mayo Clinic from 1911 to 1915 was cardiac decom pensation con idered a factor in sew of the large number of deaths from con, estue failure the rarity of thrombo is in the portal sy tem apparently excludes tasts as a significant thrombotic factor in this area Prolonged ta is likewa e has little thrombotic ellecl in varices of the leg veins in varicocele and sn she leg veins of paraplegralients Normal blood undoubtedly has all the components nece sary for intra 1a cular fibrin coagulation but the normal thrombopla tic activity 1 not ufficiently concentrated to initiate coagulation ince it must interact with the blood for a certain period Alexander belieses that closing occurs continuou ly as a normal physiologir process within the circula tion Thromboplastic activity is the mot pecific term now posible for an intricate and poorly understood mechanı m Travma olivou lt can tear the intima of a sea el and liberale extrava <ular tre ue thrombo pla din into the lumen The mechanism of platelet agglutination la ion and interaction of a platelet factor with a pla ma factor to instale thrombopla nic activly a well known The potential sites of thrombo 19 presumably are those areas where thrombopla tic activity can be gene rated in ufficient concentration--areas of endothelial damage or ta«r where there is also sufficient time for interaction of thrombotic com ponents to form fibrin COAGULABILITY How does thrombo is occur? A clinician hould probably not altempi to ay much about at Osteg " states that increa ed coagulability is probably related more clo ely to thrombopla tic activity than to any other component lacreased lickiness of platelets increased number of platelets and increased concentration of a conversion accelerating laclor have been ugge ted as accounting for the increased pridence of thrombo is m cestam pathologic and physiologic conditions 84 An unlonunate schi m has existed for years between those interester? in blood coagulation and tha e intere ted in thrombosis Robb Smith ·50 SYSTEMIC ARTERIAL EMBOLISM complains 'If one looks in any of the standard works on liaematolog) written during the last sixty years there is scarcely any mention of the mechanism of thrombosis although there will be much discussion of blood coagulation There is no agreement even regarding clotting in vitro Link 156 re gretted "the bloody polemic between experts over the estimation of prothrombin Although the disagreements in the field of blood clotting perhaps are not less sanguinary, the "coagulationists," as he terra them, are still divided The scheme of blood coagulation as worked out up to the present is illustrated well by Alexander + The intricate laboratory tests for measuring the various components are available In Tocantins 17 book Any accurate predichon for thrombows, then, must be va ed on knowledge of the relative values of the three factors discussed above The clinician knows which diseases are likely to cause thrombose and --equally important he knows the arcas in which thrombosis is }ilch to occur, but as yet he has no reliable way to identify the patient in whom it will occur Blood whether normal or abnormal does not clot at every area of damage and stasis there scems to be a thre hold value that permits thrombosis at one site but not another it is impos able to mesure either the individual or the composite values of the thrombotic and antithrombotic factors at a given site, but frequently thrombosis can be correlated with a local predominance of one factor oser another In one person the character and extent of the vascular damage may outweigh the factors of blood flow and coa, ulability although of course it is impossible to measure the character and extent of vascular damage in every site of potential thrombosis In another person fast may be the precipitating factor but this likewi e cannot be measured in a localized area Laboratory Tests There remains for consideration the coagulability of the blood All tests for thus factor face a common objection The tested blood a based sample not a representative aliquot part of the blood The talues of some thrombotic components prothrombin and its acceory and conversion factors are considered to be the same throughout the bloot whether arterial or senous, but the crucial value the rate of thrombo plastic production at the site of endothelial damage-cannot be meas ·51 PATHOGENESIS OF VASCULAR THROMBOSIS ured from a sample of peripheral blood To predict thrombose it mould be necesary to know the inherent thromboplastic potency of the site the time required for this degree of thrombopla fic potency to interact with the asailalle prothrombin to form fibris and whether the rate of flow at that particular point will permit the necessary duration of inter action Prediction te is determine the clotting time under a number of condition but none of these conditions eri ts in yo There are many rital di crepancies as well as imilarities The existence at times of a hypercoagulable sale which imtrates clotting at predi posed vascular sites is clinically accepted but not well understood Teals now available more often than not fail to detect any alterations in coagulability Irrespectuse of the degree of increased coagulability konever clotting does not occur on smpoh undamaged endothelium in a swiftly movino stream Thrombosis occurs only at certain predu pored sites Increa ed blood coagulability as a precipitating factor in thrombo k is probably of no greater importance than increa ed values for the other two thrombotic factor Thrombosis occurs frequenily with nor mally coagulable blood where the precipitating mfluence has been an 1ncrease in the degree of endothelial damage or an increase in the degree of tasis With all these factors weighed it appears that the predisposition of the area to thrombosis is more important than the predisposition of the blood The probability of thrombosis cannot be predicted by blood te * so there seems lime justification for their routine u e Stati tical data furat h more accurate predictions Farmer and Southwick 71 and others have formulated schemes ba ed on chmical correlations for predicting & patient s tendency to postoperalne venous thrombosis SUMMARY Potentially thrombosis may occur at any site of either primary in Rammation and degeneration of vascular endothelium or secondary changes following stau Specifically it greurs when the blood flow permuta suEcient time for the interaction of thromboplastin and the vd Lod kevin sad 1t you under land som thing you can mal a viod I oft and some i me later thak it was J BS lialdane wh! id that If 303 make a mod i of opething you und stand the molel™ ·52 SYSTEMIC ARTERIAL EMBOLISM other thrombotic components Since this interaction time in inois virtually impossible to measure in vitro predictions based on clinical statistical evidence are more accurate than tho e based on any blond tests now available Hypercoagulable blood occurs, but cannot ordi narily be detected An unpredictable increase in any one of the three thrombotic factorendothelial damage stasis or coagulability --may initiate thrombosis ·5 Pathogenesis of Cardiac Mural Thrombosis LEFT AURICULAR THROMBOSIS IN RHEUMATIC HEART DISEASE AURICULAR FIBRILLATION in Theumatic heart disease is as dialed an increased incidence of left auricular thrombosis irrespective of the type of mitral valse lesion The incidence of left auricular thrombosis is lightly higher in pure mitral regurgitation higher till of teno is plus regurgitation is present and very high in pure mitral teno is * It is not the lesion however but auricular fibrillation which is the primary correlate Mearli all leli auricular thromb occur in predominant miltal tendee but the lughest correlation occurs in those with pure mitral stenosis who have aurrrular fbrillation It follow then that the mechanı m of fibrillation ! Intolve an increase of one or more of the three essential factors in thrombo is-aurocular endothelial damage crea ed coagulability of the blood and retardation of blood Ron in the auricle What site de Perence becueen patients with auricular fibrillation and tho e usk sosmal shythm s tegard to these factors and why is this difference TU I greater in pure mural tenosty? Fu (3 left auricular endothelial damage more frequent in auricular fibrillation? Pathology 19 accept the presente both of Ascholl's bodies and of certain other charalien ric inflammatory changes as esidence of theumatyr opflammation There is no evidence that either of these le uns is more frequent in the fibrillating leit aurcle than in the uncle with normal rhythm A choft** bodies indicate though they are of rheumatic inflamma lion are actually rarer in patients with thromb: 69 SO The same sarity of Ascholl's bodies is con picuous in auricular fibril lation 14 146 Ato the patients with Aschof's bodies are youneet than those without this finding 1019 It appears that the acute rheumatic le jon in eather the blood vessel of the heart has httle ihsombotie poſentiality Von Glahn • has shown that there is lule tendency for thrombosis in acute rheumatic arterilis 19

·52
SYST
other thrombotic compo
virtually impossible to 31
statistical evidence are n
tests now available Hy
narıly be detected An u
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·5 Pathogenesis of Cardiac Rural Thromihosis LEFT AURICULAR THROMBOSIS IN RHEUMATIC HEART DISEASE ACRICULAR FIBRILLATION in thebimatic heart di ea e us a ociated with an increased incidence of leit auricular thrombo 1 Irrespective of the prof mitral value le ion The medence of left auricular thrombosis je lightly higher in pure mural regurgration higher styll of steno is plus regurg:13:10 » grecer and very high in pure mitral steno 18 lt 13 not the ſeason honeser but aurirular fibrillation which is the primary correlate Nearly a}} Irlz sur ular thrombi occur in predominant mittal lenos but the humbyens Correlalion Orcurs in those with pure mitral seno is Who hase ournalar Abrillation It follows then that the mechanism of fibrillation mu Insolve an increase of one or more of the three esented areas in titrompo 15-auricular endothelial damage increa el coagulability f the hood and retardation of blood flow is the aurice W723! the difference between patients with auricular fibrillassa, and theç no mai rhythm in regard to the e fartor and why 28 thu a rarre -> much greater in pure mural tenosis? First is left auricular endothelial damage more frequent in an rol fibrillation' Pathology ts accept the presence brth of Ashing to propean and of certain other tharat tersstic rflammatory char* 24 of sheumatic inflammation There is no esid nee that at the per presser le tons is more frequent » the fiboslaring left aarkl than than auricle with normal rhythm A choff's bodtes orlicative though they are of the goals fion are actually rarer in patients with thrombe* The aume tants of A shafts dies is crr port m. latvan 1 9 184 Alv the patients with lef Fitim gor than the thout the finding **> at appears that the acpie rheumator Inocente or the heart has little thrombokse slz'tt ta that there is little tendering for thromb 1 - gryte per- ·56 SYSTEMIC ARTERIAL EMBOLISM Has in 38 year old man with mural stenosis and regurgitation and auricular fibrillation-its volume wa 3200 cc 19 In mitial stenosis normal rhythm a cociated with an increa ed Ventricular fillin, gradient manifested during middle and late dia tole Catheter studies of left auricular pres ure un mitral stenosis in normal rhythm shou a giant ? "71e that pre umably reflect an increa ed auricular wy stole and pre umably accounts for the increased ventricular filling gradient 118 How much quantitate contraction the graphic record reflects and how much of a factor it is in dimini hing 1?ts in the greatly dılated left auricle is speculatie As a matter of fact there is only a slightly increaned degree of left auricular dilatation and pre sumably stasis in auricular fibrillation In a study of a group with pure mitral steno i Lew ct all found no greater proportion of large left auricles as graded bi Nuoro-copy examination in those with auricular fibrillation than in tho e with normal rhythm There i endence, however, obtained nt cardiotomy and by angiocardiography thint auricular dilatation is slightly greater in auricular fibrillation Tood"ob ered a significant difference al cardiotom In 150 cases of mitral stenosis the average enlargement with normal rhythm was 1 15 and with auricular fibrillation 178 Soloff Zrtuchni Stauffer and Kelly measuring the volume of the left auricle by angiocardiographic technics found the normal to live 100 ce As calculated from their ob eri ations the volume in pure teno is with normal rhythm was 425 cc in auricular fibrillation 543 cc Thuis four to fiefold increase would be reflected in a grerter re dual volume and consequently greater clasis particularly in auricular fibrillation neverticles the increase in degree of stais would hardly seem to be is important as the long duration of stay which fibrillation signifie The patients with auricular fibrillation had an average age of H tho ( with normal rhythni 34 Is ciner Significance of Auricular Fibrillation The chicf clinical features in auricular fibrillation are the greater age of the patient and therefore in mot cases the greater duration of the di esse The ai crage age according to Lenset al greiter in fibrillation DeGraff and Lingo found the aitrim duri tion of life after the on et of rheumatic heart di €10 has 18 years for patients with fibrillation as agunt 15 for tho e with normal rhythm The greater age at death of patients isith auricular fibrillation indicate ·57 PATHOGENESIS OF CARDIAC MUPAL THROMSOSIS that the arrhythnuia deselop later in the coure of the truatu heart di ea e As I sintmetal et al 16 tate it! not aurirular fibrillation but thin cuncurrent agnation that tearls Dkard thromla The importince of fibrillation un dentizing a prolonged duration of theurial heart ds cave It GCCUS sa frequenlly ın mural leno is with regurgita trona in pure mitral steno s and esen more frequently in pute regurgi TABLE 13- Relation of laying Thrombotic factars in Rheumatic Haral Dispase to Left Auricular Thrombosis Degree 1 erdothelial Coagulability lainake of blond Incxlence Duration of la 2173rular Short Prokmeel thermik, 0 Hinimal Mical regut Nation mal chytlum + Mara) ten) mal rhythm 0 Viral meno 1> Aur) ular hi? cilatt 4 (11 LT tai) 11der acei talo? Coincidentally st marks a prolonged duraturn of any of the e (onditions. The it identifies pure matrał teno 18 ay prolonged leht aurk ular tagnation tenosis with minimal regurgitation as prolon ed hot munerate stagnation and pure regurgitation as prolonged but ulazatal tagsatson It affects ps e the aufgal mechanı n of throm by lightls lui does in particular mark tho e patients with the greale e likelihood of thrombu 3 It the me auricular brillation appears in murat lenossens fasis prolonged but the patient is older {coagulability greater) and ite endothelium has been sutjected to the damaging effect of pro loncet 12Ali three thrombolic factors are copridentally at the makums The correlation between aurcular thrombı and adncula fil nilalton therefore predominantly measures a stati tual rather than alti ·5B SYSTEMIC ARTERIAL EMBOLISM 11 a causatne association The arrhythm, contributes little to the thirie thrombotic factors-stasis, coagulability, or endothelial damagebut it accurately indicates that the e factors are at a maximum (TAI LF 13) Prolonged rheumatic heart discose frequently gives rise to auricular fibrillation and prolonged left uuricular stasis frequently gives ri e tu lcft auricular thromboss When the e the car 211C conditions ocrur together a lugh proportion of the patients have both auricular fibrilla tion and left auricular thronbosis two independent effects 1:1 ing to gether from a common origin but a ociated so frequenth that aurio ular fibrillation is an important index of left auricular thrombo the patient with pure mitral stenosis LEFT VENTRICULAR (MURAL) THROMBOSIS In myocardial infarction, only one of the three thrombotic factors is presumably the same as in rlicumatic leart disca e--the congulability of the blood which as in rheumatic heart di esse probabil varie only according to the patients ngc The second factor the thrombotic tendency of the damaged endothelium is much higher in miocardial infarction The readiness with which thrombosis occurs cu le better appreciated when it is remernbered that although the ventricle is actively contracting and the aortic salve operrting freels the clot forms within a few days after arterial occlusion, and at times even when prothromian activity has been reduced to 30 per cent of normal Although the ven tricular wall does not contract strongly in the intmediate arcı of the infarction this localized inactivity with the remaining heart mu cle actacly contracting should have only a minor effect on the movement of blood over that area If this strong thrombotic tendency can exit without significant sta 14 at should be greatly enhanced when ata»ls is obvious Conge tive heart failure which N u urlls a sociated with left cntricular enlargement increased residual volume and resulting this is found in twce 15 many ca es of myocardial infarction with as without sentrxular eluta The higher incidence of mural thrombi in infarcts of the anterar wall is attributed by Jordın ct al 13 to the probably greater ta i at the apex in the pre ence of a large infarct especially in conge tie failuri Sunce this process can occur within a few dave alter mfarsion patients who are not in shock and who l17c no enlargement or dilata tion of the heart and little evidence of stisk thrombosi je let or counted for by an intense thrombotic tendency in the damaged endo ·PATHOGENESIS OF CARDIAC MURAL THROMBOSIS $9 cardium The more acute thus damage, the greater the tendency A Jordar et al 13 demon trated the incidence of thrombi is less in healed infarctions Why left ventricular thrombosis should bare no apparent correlation mith auricular fibrillation although it is so strongly a coriated with rongestive heart failure in which the arrhythmia frequently occurs, 1s not readıly explained Probably the relationship would appear in a larger series SUMMARY Although auricular fibrillation appears to be the closest correlate of trít auricular thrombosis in theumatic heart di ease it does not seem TABLE 14-D ferences in the Alechanism of formation of Mural Clots in che Left durcle and in the Left I entricle Left auricle Lelt sentricle Enology Rheuradt, heart disea e Prolonged stasis needed Character of atas Nonrheumatic heart disease Only short period of ta 19 Derded Mechanism of stasts Vainly obstructed outlet Nonob tructed-congestne beart failure aneury mal dulatation (early etertion alter myocardial infarction) Sess in wall t obvious Oiten mi Usually obvious Recent or cro copic No clots with old infarction Recent large acute lesions lesions form inte clnts than old small le sons Chamber Usually dilated noncon Dilatation not necessaryfracting Hall chamber has contracting wall Clinical correlation Auricular fibrillation Auricular fibrillation not a most important correlate correlate Clinical correlation Congestive failure not a Congestre failure a definite (2 correlate correlite Type of clot Frequently small and un Attacked to wail No bal} attacked in appendage or thrombs larger as a ball thrombu ·60 SYSTEMIC ARTERIAL EMBOLISM to contribute to any of the necessary factors for thrombosi--auricular endothelial damage, greater coagulability of the blood or (except in a slight degrec) retardation of blood flow It is a reflection of the pro longed duration and not the degree of stası Occurring in older pa tients with older heart disease and with prolonged stasis it indicates the greatest probability and highest degree of stasis, coagulability, and endothelial damage Although these same factors are present in arteriosclerotic heart disease they arise from an entirely different set of causes The character of the endothelial lesions in of dominant importance Blood coagulability may be normal for the patients age and sex and stasis (conge the heart failure) is important chiefly in thrombosis associated with healed infarcts The differences in the mechanism of formation of clots in the left auricle and left ventricle are summarized in TABLE 14 ·6 Pathogenesis of Systemic Arterial Embolism in Heart Disease MOBILIZATION OF CARDIAC MURAL THROMBI THE FORCES that terd to expel thrombı from the heart chambers are e sentially the same ones that normally tend to present their formation (ertain humoral factors probably fibrinolytic contenably may alter the chararter of thrombı or po sibly les, en their con tency but mechanical forces seera to be more important an aclue blood flow plus the contractions of the chamber wall In the normal heart the force of perhaps primary importance kan actre blood flow Any motion in a lquid as Iran fitted to all its parts cle keeping them in motion in relation to each other and to the solid material containing them in Suid mechanus thys is termed shearing tress and increases with the velocity of the Nou" Conrer ely, any hackerung in flow reduces the hearing tress A retarded blood flow increaves the tendency both to form thrombi and to retain them at a favorable site The chamber wall may contract actuels or lugghly or be dilated and relatively inert so that in the left ayrıcle during mitral steno is with auricular fibollation the wall may as Soderstrom implie be as defenceless against thrombotic deposits as a horc hould be against fles without ki cutaneous muscles The left ven Inicle may contract weakly as a whole or there may be localized area of weakened contraction or actual los of contraction as in aneurysmal dilatation Expul jon of thrombs from a cardse chamber is affected by a third mechanical factor-the relation of the ize of the thrombus to the suze of the orifice through which it mut pse li a thrombus larger than the sxfice of egress is lop ened it may berome lodged in the opening either m mentanly causing szacopet or longer (cau ing death) The orifire of egress of the left ventrick infrequently is natroned (aortic lenosis is inírequently associated with left ventricular infarction) but one of the main correlates with formation of left auricular thrombi 13 a narrowing of the mitral origte the ball thromby of the heart are predominantly sa the left avricle There are of cours many differences & ·62 SYSTEMIC ARTERIAL EMBOLISM in the interplay of factors in the mobilization of thrombr from the left nuricle and the left ventricle MOBILIZATION OF THROMBI FROM THE LEFT AURICLE The factors affecting mobilization in the left auricle, in addition to flow, are the contraction of the body and appendage and a po aible di tortion of the auricular wall coinciding with ventricular systole and diastole Normally, these forces are strong and effective, but in the rheumatic heart with thrombị they are obviously ineffective at leat in presenting thrombosis During the half second of ventricular diastole a normally patulous mitral valve allows a somewhat varying rate of inflox --sapid both in the early part of diastole and in the final one tenth second-during which both the auricular appendage and the body contract however in the intersening drastasis the flow is hardly grcater than the return of pulmonary venous blood to the heart This unevenness in flow exerts an intermittent shearing stress on the wall of the left aurıcle and normally tends (presumably) to prevent the attachment of platelets > even a favorable endothelial surface There is possibly a pull on the auricular wall with ventricular systole and the suction effect of sen tricular diastole These are merely presuniptive in man Prinzmetal ct al 106 have demonstrated a distorting effect of ventricular systole at times in the heart of a dog an action not yet observed in man lie movement of the auriculoventricular value toward thic apex 17th tole may induce an auricular pul] +18 A diastolic auction effect lias been demonstrated in the heart of the dog and turtle 35 141 A dia tolic auction effect iſ present in man no doubt differs in nature and degree in normal rhythm and auricular fibrillation Effect of Rheumatıc Mitral Stenosis In rheumatıc mitral stenosis with auricular fibrillation--the condition in which four fifths of left auricular thrombs are found all the ants thirombotic forces are les ened First the dilated auricle accommodate a large stagnant residual pool which cven with a normal salic would be evacuated only slowly Second the flow through the mitral value is not the normal pul atıle flow with varying rate—it remains even and steady throughout ventricular diastole with le s tendency to produce a hearing stress on the blood Third the aurıcle it elf of inert through distention is unable to expel the stagnant blood through effective con ·62 PATHOGENESIS OF SYSTEMIC ARTERIAL EMBOLISM ey fole traction (4t cardiotom; the aurıcle appears molionle ) Fourth the pre umed distorting action of sentricular systole might have less effect on a dilated and di tended auticle that is ubject to greatly increased internal pre sure In pure mitral stenosie as ob ened at operation there i no 11 ible distorting motion of either the aurice or its append age on ventricular sy tole or diastole If left auricular thrombı form they have done so through the In or reduction of the mechanical forces that normally present their forms lion If these thrombi esentually are mobilized obsou li il mut bir by an increase in those came factors such have failed to prevent their formation. There must be either (1) a change in the character of blood flow tending to increa e the heating effect nn the thromb: in tl auricle and to move loo e thrombt from the appendage into the actie current (2) a return of contractilits to the auricle or the inert oppend age or (3) an increase in the distorting effect of senincular and dia tolr upon the aurie le Dislodgement of a thrombus depend to some extent on the tenacilo of its atsekment to the wall which apparently varicy with the age of the thrombus Soder trom found that the clits in the body of the left aurkcle were veually large flat formations broadly and firmly attached to the endocardium lle con idesed these surface shtrin as he termed them evidence of an old chronic throml olic tate Ik reser encountered a recent thrombus in the body of the left aurice much touch fibrous thrombi are often cheried al nutral val oplat Quite different are the red smooth and round thrombi characteriti calls found in the auricular appendage They are of Terent formation and frequentis unattached and if so the onl factor presenting mobil ization is ta is The greate t danger of embolier is from these red and recenily firmed left auricular thrombi Belcher and Somerville found that embo, almo telnass cops I of a red thrombus which has become di lodged before organization has had time to tart Kuzman Griffith Jones and Weser 146 found top that fresh thrombir and not old organized clots are the Dutce of em!,olt 31 the red and recently formed thrombus 3s not discharged early into the arterial circulation it becomes att ched and fibrots The crucial time determining whether a clot remains a thrombus or becomes an embolys therefore 13 kortly after its formation when it ·62 SYSTEMIC ARTERIAL EMBOLISM in the interplay of factors in the mobilization of thrombı from the left nuricle and the left ventricle MOBILIZATION OF THROMBI FROM THE LEFT AURICLE The factors affecting mobilization in the left auricle, in addition 10 flow, are the contraction of the body and appendage and a po sible di tortion of the auricular wall, coinciding with ventricular systole and diastole Normally, these forces are strong and effective but in the rheumatic heart with thrombi they are obviously ineffective at least in preventing thrombosis During the half second of ventricular dı zatole, a normally patulous mitral valve allows a somewhat varying rate of inflox---rapid both in the carly part of diastole and in the final one tenth second-during which both the auricular appendage and the body contract however, in the intersemng diastasis the flow is hardly greater than the return of pulmonary venous blood to the heart This unesenness in flos exerts an intermittent shearing stress on the wall of the left auricle and normally tends (presumably) to present the attachment of platelets to even a favorable endothelial surface There is possibly a pull on the auricular wall with ventricular systole and the suction effect of ven tricular diastole These are merely presumptive in man Prinzmetal et al 100 have demonstrated a distorting effect of ventricular ayatole at times in the hcart of a dog an action not yet observed in man The movement of the auriculos entricular valse toward the བ། tole may induce an auricular pull me A duastolic suction effect lias been demonstrated in the heart of the dog and turtle 33 144 A diastolic suction effect of present in man no doubt differs in nature and degree in normal rhythm and auricular fibrillation Effect of Rheumahc Mitral Stenosis In rheumatıc mitral stenosis with auricular fibrillation—the condition in which four fifths of left auricular thrombı are found all the antı thrombotic forces are lessened First the dilated auricle accommodate a large stagnent residual pool which cien with a normal alıc would be evacuated only slowly Second the flow through the mitral vale is not the normal pulsatile flow with varying rate--it remuns es en and steady throughout ventricular diastole with le s tendency to produce ? hearing stress on the blood Third the auricle itself if inert through distention is unable to expel the stagnant blood through effective con aper with ·63 PATHOGENESIS OF SYSTEMIC ARTERIAL EMBOLISM fraction (At cardiotomy the auticle appears motionless ) Fourth the presumed di torting action of sentricular y tole might base less ellert on a dilated and di tended aurcle that is ubject to greatly inerea cd internal pre cure. In pure mitrał teno is as obserted al operation there is no visible di torting motion of either the aurile or its append age on ventricular systole or dsastole lt left auricular thrombi form they have done through the lo ar reduction of the mechans al forces that normally present their forma tron if these thrombı eventually are mobilized obylou ly it mut he by an increase in tho e ame factors which have failed to present their formation There must be esther (1) a change in the character of bloot flow tending to increase the hearing effect on the thrombı in the auricle and to move loo e thromb from the appendage into the active current 12) a return of contractility to the auricle or the inert append age or (3) an increa in the di torting effect of ventricular stole and dia tole upon the auricle Dislodgement of a thrombus depend to some extent on the tenacity of its attachment to the wall which apparently varies with the age of the thrombus Soder trom 3 found that the clots in the body of the left auricle were o vally large flat formation broadly and firmly attached to the endocardium lle considered these surface thronby as he termed them evidence of an old chronic thrombotic tale lle never encountered a recent thrombus in the body of the left auricle Such touch fibrous thrombi are often ob ered at mitral als opla ty Quse different are the red mooth and round thrombi characteriti calls found in the auri ulat appendage They are of recent formation and frequently unattac) ed and if an ite only factor presenting mahil ization is sta The greste danger of emboli m from these red and recently formed left aurular zhromus Belcher and Somervilla y found that emboli almost always comes of a ord thrombus which has become di lodged before organization has had time to tast huzman Criffith June and Meyer 116 found too that fresh thrombi and not oli organized clot are the ource of embolt If the red and recently formed thrombus is not discharged early into the arterial circulation it becomes attached and fibrotic The crucial time determining whether a clot remains a thrombus or become an embolds therefore jy hostly alter its formation when it ·62 SYSTEMIC ARTERIAL EMBOLISM in the interplay of factors in the mobilization of thrombı from the left auricle and the left ientricle MOBILIZATION OF THROMBI FROM THE LEFT AURICLE The factors affecting mobilization in the left yuricle, in addition to flow, are the contraction of the hody and appendage and a po ble dr tortion of the quricular wall coinciding with ventricular sıstole and diastole Normally, the e forces are strong and effective, but in the rheumatic heart with thrombt thry are obviously incffective, at lea t in presenting thrombosis During the lali second of ventriculır destole, a normally patulous mitral valve allows a somewhat varying rate of inflou-rapid both in the early part of diastole and in the final one tenth second-during which both the auriculır appendage and the body contract, however in the intervening diantisis the flow is liardly breater than the return of pulmonary venous blood to the heart This unes ennc s in flow exerts an intermittent shearing stress on the wall of the left avrele anti normally tends (presumably) to present the attachment of platelets to even a favorable endothelial surface There is possibly a pull on the auricular wall with ventricular systole and the suction effect of ven tricular diastolc These are merely presumptose in mon Prinzmetal et al 190 have demonstrated a distorting effect of ventricular ay tole at times in the heart of a dog, an action not yet observed in man The movement of the auriculoventricular valve toward the apex with ayatole may indure an aurirular pull » A diastolır suction cffect has been demonstrated in the heart of the dog and turtle 35 144 A diastolic auction effect if pre ent in man no doubt differs in nature and degree in normal rhythm and auricular fibrillation Effect of Rheumatıc Mitral Stenosis In rheumatic mitral stenosis with auricular fibrillation--the condition in which four fifths of left auricular thrombi are found -all the anti thrombotic forces are lesacned forst the dilated auricle 1ccommodaten a large stagnant residual pool #uch even with a normal yale would be evacuated only slowly Second the flou through the mitral alie i not the normal pulsatile flow with varying rale--it remains esen and steady throughout sentricular diastole with less tendency to produce a shearing stress on the blood Third the auricle itself al inert through distention, is unable to expel the stagnant blood through cliccine con ·63 PATHOGENESIS OF SYSTEMIC ARTERIAL EMBOLISM fraction (At cardiotomy the aurcle appears motionlea ) Fourth the pre unted di torting action of sentricular ey stolc might have less eflect on a slated and di tended auricle that is subject to greatly increased internal pre cure la pure mitral teno k as ob pried at operation there 15 70 13 ble da torting motion of either the auncle or its append age on ventricular y tole or dia tole If left avrxular thromb, forro they have done through ihe lo or reduction of the mechanical forces that normally present their forma tion If these thrombi eventually are mobilized obudou Is it mut he by an increas stoc ame factors which have failed to prevent their formation There mu t be either (?) a change in the cliaracter of lood flow tending to increase the k aring effect on the thrombı in the duscle and to mose loo e thromis from the appendage into the actie current (2) a return of contractility to the auricle or the inert append ame or (3} an increase in the di torting effect of sentrscular y tole and dia tole upon the aurcle Do lodgement of a thrombus depends to p ettent on the tenacit of its attachment to the wall which apparently varies was the age of the thrombu Soder trom 3 found that the clots in the body of the left aurcle were w wally large flat formations broadly and formula attached to the endocardium Me considered these urface thrombi as he termed the evidence of an old chronic throinbonc tale II neser encount sed a recent thrombus in the body of the left aurice Such tough fibrous thrombi are often observed at mitral valioplits Quite different are the red mooth and round thromhi character ti rally found in the auricular appendage They are of recent formation and frequentis unattached and if the onl factor preventing mobil zation is tai The greatest danger of emboli m us from the red and recently iusmed left auricular thromby Belcher and Somerville found that embol almo 1 always const of a red thrombus which has become di Indeed before organization has ład time to tart Kuzman Geelil Jone and Meyer 146 found too that fresh thromb and not old roanized rlots are the Qurce of embol If the red ard recentis Irrmed thrombu is not discharged early into the arterial c»uron it becomes attached and fihroter The crucial time determining whether a clot remains a throm) us or becomes an embolus tortelore is fortly after its formation when it ·64 SYSTEMIC ARTERIAL EMBOLISM will either become attached, organized and relatively innocuous, or become loose and be ejected as an embolus Apparently as long as the mitral valve is of normal width or widened as in mitral regurgitation any minute thrombi that may form are carried by the force of the blood flow through the patulous sale Stagnation due to stenosis not only favors thrombo 13 but allows time for a clot to increase to a size that makes evacuation through the small orifice impossible The contraction of the wall of the cul de sac (the appendıx) either diminishes or ceases and the clots are retained Ball valve thrombı rarely forn except in predominant mitral steno 1 In regurgitation, if larger thrombı do form, the relatively rapid more ment of blood and the larger orifice still favor early expul ion, the bidirectional fluctuations occurring during the cardiac cicle more effectively "milk" the left auricle than does the relatuely retarded nonfluctuant unidirectional floss of mitral stenosis and apparently a high proportion of clots are expelled 1 : Effect of Rhythm There is no evidence that either normal rhythm or establi lcd auric ular fibrillation is more likely to mobilize Icft auricular thrombı. Among 72 patients with cerebral embolism and rheumatic mitral steno is Harris and Levine 10) found nearly four times as many patients with auricular fibrillation as with normal rhythm and Humovich is found an even greater incidence of fibrillation in 92 patients with systemic arterial embolism Nevertheless this preponderance is not related to fibrillation itself it is entirely in proportion to the incidence of left quricular thrombi Certain changes in heart rhythm however occasionally arc a ociated with discharge of emboli In the change from auricular fibrillation to normal rhythm the coincidence of conscrsion and emboli m is at times cvidence of a causatne correlation The relerce honeter is apparently as frequent-embolism coinciding with either a paror; am of nuricular fibrillation or the onset of establi hed fibrillation Among 153 conier sions of auricular fibrillation to normal rhythm studied by Soholow and Ball" I only two had embolı at the time of conversion but seven had embol at the time of a sub equent relap e from normal rhythm to Turicular fibrillation Embolism occurred during prrorysms in five of 13 patients studied by the author 11 Other workers have al o oly ericd thus correlation ( 109 198 ·PATHOGENESIS OF SYSTEMIC ARTERIAL EMBOLISM 65 Sullen acceleration of the heart beat ire pective of the mechanism generally is considered capable of do lodging cardiac mural clot Claically however there is no evidence that sinus tachycardia auric ular Mutter or parotrenal supraventricular tachycardia is asociated with any greater frequency of systems arterial emboli m Embol m rarely accurs during auricular flutter regardless of the type of heart disea 11$ 145 Effect of Exertion In mitral teno is althouch exerce increa e pule rate leſt auric ular pres ure (pulmonary capıllary pre surel and the rate of mira! Salve fios in cc per erond of diastole) the cardiar output is only < elsghtly increased 59 There is no convincing clinical evidence that effort increa es emboli m in rheumatic heart di eas On the contrary Sprague and cling hou e 39 found that of -7 arterial orclu son (presumably embolic) orcurring in 38 patients with rheumatic heart disea e and auricular fibrillanon more than 90 per cent occurred during ordmary daytime aclxity and rest Fertion preceding emhol mn they concluded was coinridenta) Effect of Digitalis The timulation of digitalis might be expected to contribute to therm mobilization of left auricular thrombi although the cluel effect of the drug is on ventricular contraction which become loner and tronger There is no crucial tudy on thus question !! O A The long accepted theory that embol ma xtated with a change in thythm from auricular fibrillation to normal is raused by a return of contraction of the auricle 16 open to doubt. There are several objection Fut the dilated auticle a eciated with auricular fibrillation has not been hown to contract of the rhythm is conserted to norma! If the dilated aurcle of mitral tena is contrarts more effectively with normal shythm than with auricular fibrillation iti difîcult to explain creral other di-crepant facts hy hould embol masceut as frequentis í not more frequently sith change from a normal thythm to that of auricular fibrillation or from a more actively contractin, ayrıcle to one les actively contract ing? Why do both direct and indirert s ualization of left auricular movement fail to how differences in contraction? At cardiotom; both the body and the appendage of the aurice are inert to ordinary susjon ·SYSTEMIC ARTERIAL EMBOLISM Without inspecting the movement of the ventricle the rhythm of the auricle cannot be stated Soloff et al 7 failed to observe by angio cardiography any appreciable variation in the size of the left aurice during the cardiac cycle in patients with mitral stenosis whether the Thythm was normal or that of auricular fibrillation Any alteration of auricular contraction would not seem as significant as the abrupt change in the pattern of ventricular contraction Whether this sudden alteration in ventricular rhythm brings about mobilization of auricular thrombi is speculative Conceivably it might do so by some change in the di torting effect on the auricle of ventricular systole and diastole The nature and degree of the auricular wall pull during systole, and of a suction effect during diastole although presumptive actions undoubt edly vary with the regular and irregular ventricular contractions of normal rhythm and auricular fibrillation A sudden change in rhythm can as logically, if not more logically, explain dislodgement of an auricular thrombus than a change in auricular contraction Final er planation must await further evidence ARTERIOSCLEROTIC HEART DISEASE In contrast to the better documented picture of left auricular throm bosis and systemic arterial embolism in rheumatic heart disease les can be adduced with certainty about arteriosclerotic heart disea en primarily because the diagnosis itself except in cases of myocardial infarction or angina pectoris, is less frequently established with cer tainty and secondarily because it is more difficult to determine whether a given occlusion is thrombotic or embolic Rheumatic heart disease is fairly often mistaken for arteriosclerotic heart disease and when the two conditions coeurst the rheumatic con dition is even more likely to be overlooked, together with its contribu tion to any embolism that may occur It rarely happens though that the arteriosclerotic condition is mistaken for the rheumatic Most studies of systemic arterial embol m in arteriosclerotic heart disease merely state the diagnosis without detailing the studies made to assure that the diagnosis is correct and especially to rule out coexist ing rheumatic heart disease A typical instance in which an error would have been made without a careful differential examination is that re ported in CHAPTER 7 (case 5) Although the patient was 68 years old rheumatic heart disease was diagnosed because of disproportionate left ·87 PATHOGENESIS OF SYSTEMIC ARTERIAL EMBOLISM TACLE 15-T eft Auricular Thrombosis in dcule Vyorardial infarction Number with left auricular thrombo Per cept wuh left auricular thromt Author Patients 181 210 19 11 10 5. Soderstrom Jardan Total 1 fav 391 30 auricular enlargement in the absence of congestise heart failure While she was in another city emboh m to the cerel ral and fenioral arteries occurred and the physician there a cribed it to arteriosclerotic heart disease When the frequency of such errors is con dered it seems quite likely that the incidence of left auricular thrombo is in arteriosclerotic heart di ea e esen maller than the 8 per cent currently etimated (TABLES 15-161 and that the proportion of embols arising fross the left auricle mut then be till malles To explain tomic arterial embois m in arterio clerotic heart dr-ease therefore we mu i chilly explain the mobilization of thrombı from the left ventricle Since there. 18 eldom any valvular ob truction to theus egrees hall thrombi do not occur in the left ventricle) the inquiry mut concern itself with the mechan) m by which thrombi are detached Irom the ventricular wall presumably a certain type of contraction Since clots form un TABLE 36-left funcular Thrombosis in Chronic Arterioscleronc Heart Disease (H oled Wrocardial Interchant Coronary Artery Disease #h Hip rtension and Hypertensie Cardiovascular Disease) Number with left auricular thrombn 19 Ser cent WRTH left autorulat Chri mbosi Patrenis llealed my cardial infarction (Jordan 117 3 2) (nary cleri pluhy perlen son ver trom) }} {erten Ne Carduna cular di ea e (Soder kron 275 57 10 17 Tital and average 418 38 84 ·68 SYSTEMIC ARTERIAL EMBOLISM the presence of a certain contracting mechanism or force, a change in the contracting mechanism would seem to be the most probable cau e of their detachment MOBILIZATION OF LEFT VENTRICULAR THROMBI Rapid and regular ventricular contractions would seem likely to favor the mobilization of thrombi but in acute myocardial infarction where left ventricular thrombı are known to be frequent, there is no documented correlation of systemic arterial emboli m with sinus tachy cardia auricular flutter or supratentricular tachycardia-all of these being conditions that gne rise to accelerated but regular ventricular contraction I ob erved no embolism in 19 cases of myocardial in farction wth auricular flutter, nor in eight cases with supraventricular tachycardia 8 10 In arteriosclerotic heart disease there is no correlation of embolism with auricular flutter 168 188 If auch rapid heart rates do not induce emboli m exertion could hardly be expected to make a difference The effect of rapid irregular ventricular contraction such as is a 40 ciated with auricular fibrillation is more difficult to evaluato-pri marily because of the unreliability of diagnosis of the underlying disease in studies on arteriosclerotic heart disea e secondarily becau c of the previously mentioned doubt as to whether a gren occlusjon i thrombotic or embolic and further because digitalization almost always practiced in auricular fibrillation may theoretically contribute to mo bilization of clots If the number of ventricular thrombı formed is no greater in auricular fibrillation (see CHAPTER 3) any increase in emboli m must be due to greater mobilization of thrombı The irregular contractions of the sentricle secondary to auricular fibrillation might tend to loo on the attachment of a ventricular clot more readily than the even contractions of normal rhythm If systemic arterial embolism occurs soon after auricular fibrillation begins the change in contractions might be u pected as a cause If fibrillation has been going on for some time before embol: m occurs it is questionable whether the clot could have been mobilized olely by an arrhythma that did not prevent is formation Two ways have been suggested in which digitalis may contribute to systemic arterial emboli m in arterio clerotic heart disease At least theoretically," Fishberg Hitzig and hung 3 point out digital pre ·89 ju tifies the PATHOGENESIS OF SYSTEMIC ARTERIAL EMBOLISM Notable du pores to certain dangers in myocardial infarction among the e are mobilization of ventriculat mural thrombi in con e quenre of a more powerful systole Whether thee dangers are actual can only be established by observation of a large series of cases The econd theoretical danger from digitalis po tulated for patients with congestive failure is the decrea e in heart size which al o might tend to di lodge thromby $33 Blumer 4 warned The frequency with which thromlu are present in coronary occlusion attitude of many phy icians regarding the avoidance of medication with digitalis unle s there is ome pry definite indication for its use such az auriculas fibrillation in acute myou ardial infarction where diagnost of arteriosclerotic heart ds ease is highly accurate and diagnosis of lemuse estessa) embolien req.onably accurate the incidence of auricular fibrillation 19 so low that it is difficult to obtain a large series Some years ago I tudied a group of of patients with auricular fibrillation occurring an acute myocardial infarction $ This tudy was made prior to the use of Oscurarel elumating an important antithrom hots factor The relation of auricular fibrillation to i temic arterial embolissa 15 this group is irlere ting The diagnos of scule onlarction as reasonably certain (typical EKG es olulion) and thal of a lamic arterial emboli m bhly probable (patients with sudden hemplega or udden occlusion of an extremital artery) Forty-eight patients had congestive failure and 36 did not The variables affecting arterial thromboemboli m acute mo cardial infarction are so many that nothing more than endtcations are ju tored in es algating the mobiliziog force from statistical data The ize of the acute infarct and the presence or ab ence of congesine failure are the factors chiefly affecting the formation of thrombi Auricular fibrillation and the ver of digitals are the theoretic fartors in mobilizing thrombi that need ei aluation If one tvdjes a group with acute myocardial infarction and conges the heart failure in order to e e the effect of auricular fibrillation and digitalis the results are interesting if not conviering Aurkulas fibrillation was asociated with a significant increased incidence of 51 teruic arterial embol m--se TABLE 17 (PS 001) In a wdy of those patients with an arute myocardtal infarct congr ture heart failure and auricular fibrillation made to determine the incidence of sy temic arterial emboli ma zmong those teren ing and those not receiving digi m ·70 SYSTEMIC ARTERIAL EMBOLISM TABLE 17-Incidence of Systemic Arterial Embolism in Patients rith Acute MIyocardial Infarction and Congestite Failure in Those nuth Normal Rhythm and Those uuth furicular Fibrillation Number of patients Per cent with S temic arterial embolim Normal rlıythm 85 7 (6 patients) 27 (13 patients) Auricular fibrillation 48 tals, there was a suggestre and possibly significant increase in those who received digitalis (TABLE 1&P=001) The data in this study are admittedly suggestive and certainly heu ristic There is too a critical need for more facts What is pointed up are the difficulties insolved in evaluating the relation of auricular fibril lation to arterial emboliem un arteriosclerotic heart disease If the effect of the arrhythmia is inconcluse in a group in which the diagnosis both of the heart condition (acute myocardial infarchon) and of the systemic arterial embolism is highly accurate (the embolic episodes were typical either sudden attacks of hemiplegia or sudden peripheral occlusions), then how conclusive can studies be in patients with supposed chronic arteriosclerotic heart dı ease in whom the diagnosis of both the heart disease and the cause of arterial occlusion is lens certain? If the effects of the arrlıythmia in acute myocardial infarction cannot be divorced from the effect of digitalis how can wystemic arterial embolim in arteriosclerotic heart disease be ascribed to auricular fibrillation unless the effect of digitalis be exrluded? In theumatic heart disease auricular fibrillation can be definitely correlated with an increased incidence of both left auricular thrombosis and systemic arterial embolism In arteriosclerotic leart disease there TABLE 18–Incidence of Systemic Arterial Embolism in Group of 48 Patients uith Acute Mlyocardial Infarction with Congestne Failure and Auricular Fibrillation in Those Cuen Digitalis and those lot Guen Digitalis Number of patients Per cent with sy temic arterial embolim 39 Group gaven digitalis Group given no digitalis 33 (13 patients) 0 (no patients) 9 ·71 PATHOGENESIS OF SYSTEMIC ARTERIAL EMBOLISM no concluente evidence that ayricular fibtillation is a sociated with an increased incidence of left sided thrombi nor is there conclusie evidence that any appirent increased incidence 10 ) temic arterial embol, m attributed to auricular fibrillation cannot be correlated equally well with the administration of digitalis in those with congeetle heart failure SUMMARY There is no adequate explanation for the mobilization of left auricular thromba in the majory of in lances The occurrence of emboli canh not be correlated with anything aje occasionally a change in the rhythm of ventricular contraction from a regular to an stregular rhythun or vice versa An increa e in ventricular tafe alone if regular does not increa e the incidence of embolism There is no evidence either that crerci c tends to increa e the mobilization of left auricular thrombi not there correlation of emboliem with a regular tachycardia uch as inus tachycardia auricular Bulter or patorjemal supraventricular tachycardia TABLE 19-Vechanism of Mobili ation of Left Auricular and Left Ventricular Vural Clors I eft auricular Left ventricular Istrediate mobilizmg factor Related to type of fiow Related more to con not contraction of traction of ventricular articular wall Wal] Relation of arrhythmias No correlation ho tutelat I legular tachy ardia ? Rapid yegolar rhythm No correlation will lo correlate na nithe -auricular fibrillation e tablı hed rhythm tabli hed rhythm 3 Sudden change of Oca onal, but N lenguh euidence thythm of malto d finite auricular fibrillah >> auricular fibrillation normal Ditalis correlation A suggestise correla tion but it enough evidence Exertion No correlation Na correlation ·72 SYSTEMIC ARTERIAL EMBOLISM Mobilization of left auricular thrombi in rheumatic heart disease therefore must be regarded in the main as a fortuitous event Mobilization of a left ventricular thrombus occurs if a clot is detached from the wall None is retained as a ball thrombus A change in the contraction of the wall probably accounts for the dislodgement There is no demonstrable correlation with rapid, regular ventricular contrac lion and any correlation with auricular fibrillation is complicated by the consistent use of digitalis Digitalis induces two changes in the contractile mechanism possibly conducne to the evacuation of left ventricular thrombı (1) a more powerful systole and (2) a reduction in size of the left ventricular cavity A summary of the mechanism ini oled in the mobilization of left sided cardiac mural thrombuis given in TABLE 19 ·7 Differential Diagnosis of Rheumatic and Arteriosclerotic Heart Disease ROFLMITIC HEART DISEASE and attetio clerotic heart disease differ in the danger of 7 temuc artezial embaham nhich the present and in the stiferia delermining whether and what prophylartic antsthrombotic mea ures are indicated in this connection it is crucially umpalan 10 recognsre rheumatic heart di rase because (1) it probably sccounts for most s temi arterial embolism (2) it is unserognized during lile elen in a bigti proportion of patients wath gro s miral tarzla drecque (3) by excluding its posibility the diagnosis of arterio clerotic heart di case can be more confidently made and acted upons and (4) the treatment is by po m aps the same even during congezse heart failure Whereas coronary arterial do ease may remain undetectable until it mamfests itself in acute myocardial ininction er um 805na per Corus hypertensile cardiovascular disease veu8"s nad dubicule to dragnee Rheumatic heart di ease of uspected hould be diagno able no mo tintance vi not always during Ife and belore it causes serious di ability Important procedures for differentiation between Theumatic and arterialerots heart disea e include auscultation in the left lateral po non roentgenograms (not merely Qunta cons} » the pondero anterior right ablque and left lateral po vions and plectrocardiography Dottes Bw has empha yzed the importance of roentgenograms in addition to fluoroscopy lo determine enlargement of cardiac chambers INCIDENCE OF UNSUSPECTED RHEUMATIC MEART DISEASE The incidence of un uspected theumatic heart disease in all degrees 1 probably enormous Fa stender? Pal' and Anderson 106 and others hase hown that its minor tigmas occur in a large proportion of per sons and Lichtman and Mgvp!! found gross rheum: 3tic valvular aamare at necropy in 52 per cent of 342 patients over 50 years old with anatomie esidence of keass & Case Viore important these grous Takaisar deformities are often unter ognized during hie Although 73 ·74 SYSTEMIC ARTERIAL EMBOLISM rheumatic heart disease is often wrongly diagno ed as arteriosclerotic heart disease for example, in 15 of 50 cases that hauſman and Polia hoff 1 1 found at necrop , the reverse error seldom occurs Similarly when the tuo conditions coexist, arteriosclerotic heart dı ease is u ually recognized and rheumatic heart disease overlooked According to Card ner and White 83 the coexi tence was recognized in only 7 of 32 cases Arteriosclerotic heart disease was mi sed only five time, but rheumatic lieart disease 21 times PATHOLOGIC STAGES OF RHEUMATIC HEART DISEASE Tre fairly definite stages of rheumatic heart disea e preceding clinical embolism may be recognized pathologically (FIG. 8-12) Theve ورود Fic 8 Stage 1 Acute rlieumatic carditis Rheumatic verrucae on value margins Thickened corrugated patch of auriculitis on posterior wall of auricle ·DIFFERENTIAL DIAGNOSIS OF HEART DISEASE 75 overlapping tages cannot be eparately identified clinically in every patient but lould be u pected and earched for Stage One Acute rheumatic cardite may not be recognized But when insolvement of the left auricie pre umed (F1C 3) at 1 Stage Treo Progre rechange in the mitral valve and the left auricie result in deformity of the miral vahe cay mg eno regurgitation or i th th increa ing tenai there is u ually a concomitant dilata tion of the lett auricie to an unpredictable degret - light modernte or marked FIG 9) F9 ta I soge se anal mcal clanes suth nattning of 1917a! ohce and auricular dilatatia with beginning ta Chordae tendineae Artened and thu kened Per ) 11 dtk it ayriculiti ·76 SYSTEMIC ARTERIAL EMBOLISM Stage Three Maximal deformity of the mitral valve and maximal dilatation of the left auricle probably arc reached in ten to fifteen years (FIG 10) FIG 10 Stage 3 Maximal tenost of vale and maximal dilatation if auricle Varked dilatation of auricle P'er ting auriculita ·OIFFERENTIAL DIAGNOSIS OF HEART DISEASE 17 Singe Four The formation of thrombi is folloned Mentually fin niobilization of approximately 50 per cent (FIC II) F14 11 ha ett mati naf leit auricular ihr mbi following prolone! tent and auricular til turi le djated small thr mi at site if anti uisti ani fetheen trabeculae carnere in the auricular appendage

·78
SYSTEMIC ARTERIAL EMBOLISM
Stage Fre Minor and usually unrecognized astemic arterial con
bolism (FIC 12)
練
*Y SY
Fig 12 Stage 5 Mobilization of mall thrombı as emboli u ually unreco.
nized

·DIFFERENTIAL DIAGNOSIS OF HEART DISEASE
19
Stage Sir Obrjous serious emboli m (FICS 13-15) which may be
quickly fatal
K
FIC 13 Stage 6 Stage of mobilization of large thrombı as major recog
nized system arterial erabola

·80 SYSTEMIC ARTERIAL EMBOLISM Fics 14-15 (shown side by side) Steno i of mitral orifice and thrombo i of left auricular appendage producing embolt m to abdominal aorta with Jesulting gangrene of bosh lower extremiti (Ny perm son from Could The Pathology of the leart Springfield Ill Charles C Thoma 1933 chap 8 [Dr A H Baggen to s] p 668) CLINICAL DIAGNOSIS OF RHEUMATIC HEART DISEASE Important to the chnical diagnosis of rheumatic heint di rac is the recognition of two preceding places. The first an acute upper re pir atory infcction with an as ociited streptococcal pharyngitis In about three per cent of the patients with Group A beta liemolytic streptococci acute theumatic manife tations with endocarditi occur after a latent period (a few days to six weeks) It imposible howeser alwaya to recognize an upper respiratory infection as streptococcal and cau ative . of rheumatic fever or to diagno e the acute rheumatic condition the econd phase from its signs and a; mpitome ·DIFFERENTIAL DIAGNOSIS OF HEART DISEASE As the direct cause of theumatic lever is not known and cannot be te ted for the diagnosie mut be ba pd on the relatise importance of whateret major or minor findings are present and therefore can only be presumptise lo childhood the disea e frequently meet the accepted criteria established by Jones 139 Rigid as the-e criteria are they adent tedly exclude a certain proportion of ca es of true rheumatic fever and it i felt that the imposition of lifelong penicillin admını tration based on a fal.e diagnosis is a greater hardship than the posible equelae in the event of unrecognized theumatic feser After adolescence the diagnostic problem is far more complex Acute Theumalic infection buth on the original attack and is recurrent epi odes » frequently med Jones major criteria for diagnosis are rarely satufitd on the adult and the minor features are either ah ent or of doubtful gnificance There are thus few clinical findingto warn of impending rheumatic cardstis Many middle aged pacteals in the chronic tage of theumatic heart di ease gue no hi tory of pre ceding treptococcal infection or of rheumatıc feser Such was the case with 52 per cent of 324 muddle aged patients studied by Rosenthal and Feigin (32 cases) * Sprague and Carmichael (115 ca es) -1 Apprl and Ko man (71 cases) and Hebbert and Rankın (106 casea) 113 Causes of Error in Diagnosis There are several cau es of failure to diagno more than one third of all ca e of rheumatic heart di ease during life Fit a ply icran may not see the patient or if only late in life The disca e often runs a benign cour e giving rise to no characteristic signs or symptoms before dealh results from another cause or symptoms may not occur until late in hfe giving the phy ician no opportunity for early diagno 19 A well known in tance of benign mitral stenosis unrecognized until Id age is that of Dr Herman Vickers described by White and Bland Mot of the unrecognized rases have houestr been seen for the for time in middle age The main and correctible cause of mising the diagno 18 of rheumatic heart di ease in patxents who have not prevı ousis seen a physi lap is the frequent failure to suspect and earch Dr it in persons past 40 years of age except when findings definitely point to itThe emphasis placed upon sheumatic heart disea e as e sen Lally a condition of younger per ons has obscured its high incidence i al degrees of severits in the middle aged and elderly Rheumanc ·80 SYSTEMIC ARTERIAL EMBOLISM 2 Fics 14-15 ( lown ide by side) Stenosis of mitral orifice and thrombost of left auricular appendage producing emboli m to abdominal aorta with resulting gangrene of both lower extrenutie (By permi sion from Goull The Pathology of the Ileart Springfield III Charle C Thoma chap 8 (Dr A H Baggen to s) p 668 ) 1933 CLINICAL DIAGNOSIS OF RHEUMATIC HEART DISEASE Important to the clinical diagnosis of rheumatic heart di ease is the recognition of tivo preceding phase. The first as an acute upper respir atory infection with an associated streptococcal pharyngitis In about three per cent of the patients with Group A heta hemolytic treptococci acute rheumatic manifestations with endocarditis occur after a latent period (a few days to six weeks) It is imponaylle however always to recognize an upper re piratory infection as streptococcal and cau atie of rheumatic fever or to diagno e the acute rheumatic condition the second phase from its signs and symptoms ·DIFFERENTIAL DIAGNOSIS OF HEART DISEASE Whether a ociated with auricular fibrillation or with normal rhythm rheuinitie heart disea e in middle age is unrecognized with about equal frequency The problem is to detect or to exclude Theumatic heart drea e when no previous sign is given the cases reported in this chapter illu trate how many have been erroneou ly treated because a careful differential dia no is was not made in one the diagnosis was made only becaute eroboli m forced ils con ideration and in others becau e our former mi takes had laught us always to apply the direct query Have we excluded rheumatic heart di ea es Only by adhering to this precaution can rheumatic heart di ea e in middle age he found and treated Diagnosis of Mitral Stenosis The mot reliable criteria for the diagno is of mitral trno is are au-cultatory and roentgetzalogic findings Electrocardiograrns str at tim s of value in directing attention to the lesson it cannot be too trongly empha ized that auscultation is frequently the only means of diagnor and often the characteri tic dia tolic murmur can be elicsted only with the patient on his left ide Careful au cultation in this poi tion with the breath held after expiration should be routine in the etamination of all patients in whom heart disea e is su pected Tro frequently this is not done in the following four cases emboli moc curred before a diamo is of rheumatic mitral teno is was made in three the chararteri tic murmur had not been heard before eml oly m probably becau e a rare sul search was not made in the fourth the patiert had not seen a physician before the embolim occurred Case 1 - 62 year old housewife had been well until about fire wechs We are examination At that time she had felt fatigue anú honne yol breath and had been given droitalss lien for 1 een in December 1930 ele na moderately dyspner with a vital capacity of 3 liters A totally orregular brani beal Ma hown by electrocardigraphy to be auricular fibrillation with premature besta la murmurs were noted but ko examination in the I ft lateral p iton was made Under treatment the compen 3tion returned Iut the auricular filarstation ne red Th blood pre ure was 130/80 Rentgenogram of the heat showed slight enlargercent of the left sentricle but ) eudenic of enlar,etrest of the left aurcle The tentative diagno! atten clertc ) can disease auricular fibrillation and congestive Teart failure until no ubsequent epi odes were considered possibly attsbutable to abolism On one occa ion there was mere pain in the tight co 1 sert bral angle Da the other acca on the ratient suddenly lad doabl u lon could not walk raight and bad to lean against a car ка ·82 SYSTEMIC ARTERIAL EMBOLISM heart disease unless obvious, is usually diagnosed as arteriosclerotic heart disease The correct diagnosis of heart disease in middle age will be made more often if rheumatic heart discace is considered a pre umptuse diag nosis in cvery cardiac patient, esther alone or as an associated condi tion, until proper studies have been made to exclude it Auricular Fibrillation in Middle Age If auricular fibrillation is seen for the first time in middle age or later, without obvious etiologie findings and no reliable hi tory 1 obtained of acute rheumatic ferer or acute rheumatic cardılı, the arrhythmin more often than not is diagnosed and treated as nonrheu matic heart disease unless a critical differential study as made A hi tors of rheumatic feser would be of lielp but as noted above the acute stage is missed in the majority of patient. Moreover a careful inquiry Te garding a past medical history of the various manifestations of rheu matic fever usually is not made The questioning frequently 15 cursory indifferent and unrewarding I have also been frequently remiss (Ca e 7) It is of more than academic interest however to di lingur h be tween rheumatic and nonrheumatic heart disease as the cau e of auric ular fibrillation The indicated trcalment can vary in many exccntial and critical detail Several specific measures may be indicated of Theumatic heart disease is the cause continuou- prophylaxis agunt recurrent streptococcal infcrtion mitral vals oplasty of mitral steno i is present and antithrombotic mer ures of embolism occur When auricular fibrillation is associated with rheumatic mitral stenosis, the probability both of primary and of recurrent s temic arterial embolı-m is significantly greater than when a sociated with chromc arteriosclerotic heart discase The Lnºis for probabilits in either case is the incidence of thrombi in the left auricle or ventricle If auricular fibrillation occurs in association with theumatic Icart disease the cliance of a left sided thrombus varies from 50 per cent in general to about 75 per cent of pure mitral stenosis present *3r in arteriosclerotic heart disease the chance is only about 33 per cent and is no greater in auricular fibrillation as evidenced h; txo audie! In neither of these groups did auricular fibrillation increi c the inci dence of left sided clots In chronic nonrheumatic heart di case in fact there is an entirely different correlation thr left sided thromba ase associated chrefly with congestie failure 8 ·DIFFERENTIAL DIAGNOSIS OF HEART DISEASE auricle Thie electrocardugram hoxed normal inus rhythm and notched 1 Wales The patient gave a hi tory that included an epi ode in July 1951 characterized by his wife said) mental confusion ome uncov rdinalin in walking and sli,bt dysarthria Thee ymptoms were fran jory and he did not consult a phy leian At the age of mine he had had an attach of acule rheumati leser but a diagnosis of theumatic heart deca e hall never been made Potentially serious emboliem (Ca eg 1471 thu may be the firt evidence both of left auricular thromł osis and of the underlying theu Fic 16 Tracia skrning abnoſtoal band P wases in lead matic heart disease The discovery then may be at the cost of hemplegia the lo s of a leg or death The mortalıly due to emboli m in middle aged patients with rheumatic heart disease is high 113 Unfortunatels although the greatest danger follows the onset of aurxular fibrillation the arrhythmia frequently cau es the characteristic purmurs to dis appear the early dia tolic the mid diastolic and particularly the press tolic The murmut may be atypical in quality Intenity or timing 114 Probably it is because of this masking that mitral tenosis as a cause of auricular fibrillation was e fimated by two authors as only 36 per cent in 79 case Win The proportion is prcbably too lon Roentgenologic Study Man of the m takes in diagno ing thpumatic heart di ease as arterio clerotic heart disease in middle age could posibly be avoided if a ·84 SYSTEMIC ARTERIAL EMBOLISM for 15 minutes before she could proceed After thi second epi ode embolism was suspected and auscultation at the apex in the left lateral position revealed a definite low pitched diastolic murmur More careful questioning revealed that she had rheumatism of the knees in childhoi The diagnosis was changed to rheumatic mitral stenosis with left auricular thrombosis and systemic arterial emboli m În a Cabot case report from the Meu England Journal of Medicine it will be noted that embol m preceded the ob ersation of a late dia toliu murmur typical of mitral stenosis + Case 2-A 66 year old hou ewife lad for three months palpitation shipping heart and moderate dyspnea on climbing three flights and she had been receiving digitalis Then fever and upper abdominal pain developed she was operated upon for acute cholecystitis and cholelilna s At this time ascultation disclo ed a grade 2 apical systolic murmur and a totally irregular rhythm The aortic second sound equalled the pulmonic 'On careful questioning there was no history of rheumatic feser Ten days later sudden coldness and rallor deseloped in the right Jeg No pulsations were palpable below the right femoral artery Tromexan and Dicumarol were administered Two days later a cardiologi i de cerned a definite grade 3 mıd diastolic rumble at the cardiac aper with press tolic accentuation Case 3~ Another pertinent case i that of a 64 year old engineer who had been well all his life sare for a bad ore throat at the age of 31 There were no joint or muscular pains everal weeks after the attack Since that time he had worked without aick leave and had never noted shortness of breath in exertion palpitation spontaneous pain or ea fatigability One evening he noticed some weakness and awkwardne lus right hand and right leg though he walked without difficults After a good night s sleep the leg seemed normal but the hand was weak and mept The blood pressure that day was 141/81 in the right arm and 134/81 in the left the rhythm was regular No murmurs or accentuated sounds were beard eher in the upright or the supine position lie was not examined in the left lateral position Becau e of the patients afe. and the absence of cardiac murmurs the tentatise diagno us was cerebral thrombo is The next day however electrocardiograms showed abnormally prominent notched P wales in lead 2 (F1c 161 On crreful ausculation with a bell stethoscope with the patient in the left lateral po mnon di tinct and low pitched presystolic rumble charactert tic of mitral steno was heard but only over an area about one and one lalf inche diameter Case Nr F age 63 was first een in January 19,6 following tuo short conyulane epi odes There were no presious system to aufge! heart disease Plissical eramnation resealed a rough low pitched press tolic murmur at the mitral area and a cardiac roentgenogram in the right oblique position showed a traight left border and enlargement of the left ·$$ DIFFERENTIAL DIAGNOSIS OF HEART DISEASE auscle The elecite cardio sam h ned normal inus rhythm and notched 1 wales The patient gale a tutory that included an epnde in July 1954 characterized by his wife aid) mental conlu on ome uncoordination 10 Walking and light dy arthria The e ymp sms were tran Klory and he did not chp ak a phy irian At the ace of mine he had had an attack of acute rheumatie fever but a diagn is of th umalic heart di ea e hail ne er been made Potentially serious emboli m (Ca es 1-4) thus may be the first esidence both of left auricular thrombo is and of the underlying rheu JEDNOTLINE Fig 16 Tracing howing abn mal bifid P wares in lead ? matıc heart diease The discovers then may be at the co t of hennplegia the lo s ol a leg or death The mortality due to emboli m in middle aged patients with rheumatic heart di ea e » hig'lz 113 Unfortunately although the greatest danger follows the onset of auricular fibrillation the arrhythmia frequenth causes the characteristic murmurs to de appear the early diastoln the mid dia talic and particularly the presy s. tolic The murmur may be ali pical in quality intensity of timing is Probably at 13 because of this masling that mitral teno is as a cause of auricular fibrillation as e tunated by two authors as only 36 per cent in 95 case 1 15 Thi proportion i pre hably too low Roentgenologic Study Many of th my takes in diagno ing theute stic heart disea e as arterid el roti heart di ease in middle age could possibly be avoided if a ·86 SYSTEMIC ARTERIAL EMBOLISM roentgenologic study for left auricular enlargement were made The absence of a diastolic murmur in a patient with auricular fibrillation does not exclude theumatic leart disease, and reliance must be placed on subsidiary findinge 151 A characteristic roentgenologic pattern, to gether with the arrhythmia justifies a tentative diagnosis es en without other findings and stimulates a more critical appraisal of signs and 19 - F1c 17 Enlargement of the left auricle posteriorly displacing e ophagus ·DIFFERENTIAL DIAGNOSIS OF HEART DISEASE symptoms with earlier recognition of one of the mall and le s serious as well as the large enous emboli Case SA 66 rear old woman we djured in a fall locidental fp examuation, he was found to have auricular fibrillation A diagnosis of arterio clerotic heart di ease was made On re-examination 18 months later she had noted no dy pnea other than slight hotnes of Ireath up a cumbino tairs, which she attributed to her ace She felt that po bly she ured more easily than she hould Auricular fibrillation was 1;}} pre ent the blood pressure was 162/100 and the sentricular rate was 96 no dia folic murmur could be detected in the left lateral position lew basai lun tales were heard bilaterally There was no peripheral con e lion or edema Fluoro Copy Tescaled enlargement of the lelt teatricle and ome tortuosity of the aorta In addition roentgenograms in the riglut oblique on Jeſt la eral positions showed definite enlargement the left auticle (F1 101 This probably repre ents rheumatic mitral stenosis de ple the all ene of any diastolic murmur In September 1956 at a e 70 and while traveling she suffered cerebral and femoral arterial emboli m The diagra is way arteriosclerotic heart dı ez e There are cieral differentiating points between the left auricular e largerzent found in auncular fibrillation in Theumatic heart 0 case and that in arterio clerotic heart disease in theumatic heart disease the left auricle usually is markedly enlar,ed and there need be no con gestive heart failure 4The left autis! kas failed because of mitral ob truckon the chamber is the ite of primary failure which precedes net heart failure In arteriosklerotic heart disease honever the left awice is eslarged only lightly to moderately the left ventricle 1 always enlarged and congestive heart failure 1 pre-ent The left auric ulas failure is econdary to left ventricular failure and absequent to congestive failure Thus f a leit auricle is enlarged out of proportion to the i ft ventricle and congerine heart failure 13 absent at 15 good presumptne extdence of theumatic heart disease This was true in case 5 Case 6 When a 61 year olf woman was seen at home for a cold her heart was found to be fat and musing She had no preceding borinex of breath palpitation of unusual fatigue The diagnosis of aurular Gibralation was confirmed by electrocardio ram The blood pre sure was 132/86 To diast lic murad s could be heard in the left lateral position Etter then or later The contour of the heart in the right oblique an! left lateral vers ladicated left zurruas enlargement the retrocardic race kas encroached upop be left border abnormally sraight and char acters tic et rheumanc mitral heart disease Inquiry brought out that the patient had frequent "rheumatic leg aches as a child 9 OYLIND ·88 incent * SYSTEMIC ARTERIAL EMBOLISM Fic 18 Right anterior oblique left anterior oblique and posteroanterior views showing calcification of mitral valve in rheumatic mitral valvular disease (Figures 18 and 19 reproduced by permission of the Department of Radiology Univerity of Southern California School of Medicine ) ·DIFFERENTIAL DIAGNOSIS OF HEART DISEASE dia nos of regmatic palsuliti he will be ob ersed carefully for char acters the mots and endence of minor enbolim A clinician need not be reluctant to diagno e mitral term is een in the ab eace of left auricular dilatation í other findings are in mificant, He must remember that the finding is fre ed as a clue and not a prerequisite to diagnosis It 19 not al25 pre ent and even when prevent is not always roentgenologically evident! trather rentgenographe finding hokeles an inariable inder af mitral teno us A calified mitral valse las distinguished from calcı fication of the annulus fibrosus) of honn by roentgenography us con rdered conclusise endence of mitral leno i whether other signs are Present or not "FIGS 28 and 19) So man e timates that 10 per cent of the patients with sheumafie mitral seno is hase u sble calcification of the mitral valve but undoubtedly it een in only a very mall proportion of these patients-probably because it is not u pected and a careful roentgenographic examination 14 not made So man finds fluoroscopic examination with optimum arcmmodalıon of the eng more helpful than the roentgenogram hich hp ay tasels adda any ching of the fluoro Lopic examination is carefully done Riebe) 19 Texently repmphasized the precs e preparation of the eyes that is neces Sart of red gogules are uued The use of hort duration roentgen er Tosure 12 to 3 mesecond ) *I probably be of more diagno fic value than fluoroskopy Dotter + halseres ( ing radiologic findings as the basic evidence Souman cla sifed patients with ubchnical tril di cac into smeral division Fur ? all group with unequinocal roentgenographic but inconclusie clinical gny for none at all) of mitral dt ease Second the largest group tho e with defaste roentgenographic findings of mitral drea e in whom the phy scal signa hale not been detested prehously by one or more competent phy ician although they are discernible when earched or Third palients with Toentgenographic evidence compatible with antal dysea e but not dagno ik ind a ociated with no other clinical sign Electrocardiographic Changes The mportance of the elertrorardiogram in patients with normal thithe illu trated in case 3 tot until the electrocardiogram was in pected as theumatic mitral teno 13 u pected A definite notched Pngle in the electrocardiogram of a patient with a clear history of ·90 SYSTEMIC ARTERIAL EMBOLISM Fic 19 Pusteroanterior right anterior oblique and leſt anterior oblique Views showing calcification of annulus fibro us of the mitral vale in nonrheumatic heart disease Typical C shapes or J shaped calcificalinn ·91 DIFFERENTIAL DIAGNOSIS OF HEART DISEASE previous rheumatic diseae makes theumatic mitral teno is a highly probable diagnosis eren in the ab ence of definite apicultafors of other igns Fraser and Turner S studying 2000 unselected cardiograms found notched P waves only twice in the absence of mitral valvular di ease. Conversely the notched Pyase is present in mot cases of pure mitral teno u In 115 patients with normal rhythm submitted to surgical treatment for mitral tend is the same authors found broad or bifid P waves in 92 per cent Presumptive Diagnosis In certain in tances a tentative dugnosis is justified on relateh few findings Acrording to Levine and Love!" One can make a pre sumptive diagno is of mural stenosis in any palient with a past hu lori of sheumatic feser af auricular fibrillation 19 present Case 74 69 }ear old man had a laroxy m of Buricular fibrillation which was terminated with everal do es of quinidine Following the epy ode there was no significant dyspnea palpstation or fatigability The blood pres ure on several observations was never lugher than 120/91 na dua tolle murmurs were audible In the sub equent five months there were several short periods of paroxysmal auriculat fibrillation (of which the patient was acutely aware) relieved by quinidine and al o-notae ociated with the e paroxysms or the u e of the drug-several eps odes of light beadedness la ting for several hossrs and accompanied by di turbance of the son e of balance Fluoroscopic examination following barium dosage gave no endence of enlargement of the left auricle After Rit months of Dadering the dia_nosis of arteriosclerotic heart di page more careiul questioning di elo ed how cursory our original rarestation of the past medical listory had been The pstient had repeated attachs of "infam matory rheumatism in childhood and adolescence Despite the absence of dustolic aurus or of derson (rable enlargement of the leit aurice rheumatic valvulji19 29 considered a more than remote posibility because of the childhood disease and the attacks of fbrillation The spells of light beadedness are possibly due to minor embolism and further embolic eptsodes will be continually suspected Even thou, sbese are only minimal criteria for a tentative diagnosis of beumatic heart disease the patient will receive the benefit of maximal observation RECOGNITION OF EMBOLISM Perhaps the most important point of al} in the management of sis. tpmr arterial embols m in theumatic heart disease is the recognition of the mall emboli that usualły precede major embol m Proper manage ment (CH 4PTER 8) can enormou ly seduce futute embolism The ·92 SYSTEMIC ARTERIAL EMBOLISM mortality from small emboli k nil but small emboh if unrecognized and untreated are frequently and soon followed by major embol which may kill or maim thc z3tient Once the diagnosis of rheumatic heart disea e has been made the clinician must consider embolisin in the differential diagnose of every condition that can arise from it Only a very small proportion of sys tenuic arterial emhols are rlıntrally recognized chefly the major ones Even then the diagnosis frequently is made late The earlier and minor emboli may c cape recognition-fir t becausc thc signs and symptoms are «o alight that even the patient fails to notice them second, beenuse the physician does not suspect their occurrence third because minor signs and symptoms of embol m are not sufficiently inic ligated and Inst because arterial pules are not recorded carls in vil patients with rheumatic lic art disease In prtients with auriculi fibrillation especially pain in the co to vertebral angle should be considered as renal embol-muud aignificant microscopre lemnturin should be sought Intrucnous py clogrima should be made of puszhle ice ab ince of renal function may identify the lesion 15 Transitory fautness and dizzines loull excile. suspicion of sma!? cerebral emboliwhich frequently cau e the symptom experience the significance of mot of these cpi odes to unrecognized Mesenteric arterial emboli m unlen surgically trented us frequentis fital Abdominal pain nau ci and vomiting may be the symptoms ami unless emboli m is considered the patients chince of surssing re ec tron 19 imperild Mesenteric embolism my ma querade as acule pendicitis 161 4G Recording Pulses One of the most important measures for the curly detection of periph eral embolian is the frequent obseruation and recording of pules By this means arterial occluscous may at times be rientified cyen though not suspected in the extremities impairment of arterial pulation may be the only means of diagno is in the ab ence of major signe inic mptoms 10 On auspicion of embolism pul e recording may lie the confirming datum Richard " declares The idea that embol, mis a condiv> with a dramatic onset 384 trially as ex rated *ith an se one » } dies hard Of 48 cases of peripheral emboliem słuch hit olurves the 17 In my ·DIFFERENTIAL DIAGNOSIS OF HEART DISEASE onset of 11 was marked not by udden pain but by numbness or cold ness of the extreranies. Haimovici 19 carefully recorded the mode of onset in his 240 ca es and found that in 28 pain or pumbnes and coldne s developed gradually Madoff Thompson and Strieter 16 re corded a case where the patient had no complaints but coolne s of the extremities led to the finding that pul es were ab ent beyond the femoral Tessel Saddle embolus of the aorta was the diagno is In addition to rai ing the u pirion of embalı m or confirming at pul e palpation may al o identify the ite of occlu jon permitting , preci e surgical approach Griffiths 103 apparently recorded the fort in tance in which emboli m to the bifurcation of the common carotid artery was diagnosed from the sudden on et of hemiplegia and coincs dent loss of pulation Kolden 16 who records a unilar in tance he lieves that caroud embolism occurs more often than is suspected ince the rarotid pul ations in the neck are celdom palpated Dunning" de cribes a method of pharyngeal palpation to detect acclu ton of the internal carotid artery Bloomberg Blumberg and Hammosexcite a case of addle embolism in the aortic bifurcation orcurring after mtrai valvopla.ty in which no one could recall haung felt the femoral artery pulses before operation I have observed another case in wluch the same oversight led to incorrect localization of the embolus, Silbert emphasizes the need for routine determinahon of pu) es in all extrem ties and for constantly remembering the po sybilny of emboli m Since either the dor al pedal or the posterior libial pul-es or both may be ab ent in norma) per ons is Silverman ind Morrison have shoka 11 is obviou ly urgent to note this ab enre before there is any reason to su pect embolism If mitral val opla ty is to be performed it is of great value to know whether there has been previous embolim The risk and difficulty of mitral valvopła ty is greatly increased if a throtabus has formed in the leit auncle When the e thrombi are tot suspected and special precaurrons not taken there is a high inci dence of emboli m at the time of operation The early recognition of embol m occurring during operation is mandatory A patient may unne a ucrea ful operation only to succumb to a belatedly recog nued saddle embolus In many eirls cases peripheral arterial embol m Has diagnosed only when the patient recovered from the ane these with a pain in the leg 11 The best method of detecting uch embolism early is to record the pulses before during and alter valvoplasty rather ihan to wait for 15 ·94 SYSTEMIC ARTERIAL EMBOLISM development of obvious symptoms Tropea and Entine so specify that the carotid pulses and those of the extremities should be recorded after the operation while the patient is in the operating room Boyd makes a similar recommendation If an embolus does lodge in the common carotid arter), and is recognized early it may prove amenable to surgical removal For this reason it is adusable that the anesthetist feel the carotid pulse frequently throughout the operation Madoff, Thompson and Strieter 1 specify precise measures for determining the status of the pulses Before operation, they examine all accessible pulses and then mark with indelible in the exact site of any pulse that is difficult to palpate so that the pul e can be rapidly checked at any time If the condition of the pulse is questionable oscillometric examinations are indicated Regarding postoperative pre cautions they reported from this time forward the status of the peripheral pulses is determined and recorded at hourly intervals for 48 hours This can be done casily and quickly by nurses as well as house officers since the location of the pulses has prouou ly been es tablished" The same procedure should be observed after embolectomy which is often followed by recurrence that may go too long unrecog nized unless the pulses have been carefully recorded Klingensmth and Theis 140 report that 6 of 19 patients undergoing femoral or iliac embolectomy died in the hospital of ubsequent emboli In 27 embo lectomies reported by Taylor 14 there were seven deaths and only four recoveries from sub equent embolism Angiocardiography The knowledge that a left auricular thrombus was pre ent would alert the clinician to the high probability of emboli - (50 per cent), if no operation were performed and the surgeon to the increased danger of embolı m during operation Visualization of left auricular thrombl through special angiocardiographic technics has been demon strated, but as yet is not perfected Large filling defects produced by both auricular tumors and auricular thrombi line been demonstrated Steinberg 33 has seen a clear cut instance of a left atrial mural throm bus in rheumatic heart disease demonstrated by angiocardiography and verified by autopsy Ile wrote me that unfortunately the c films could not be located The fir t published angiocardiogram to show a left auricular thrombus na that of Soloff and 7atuchni (FIC 20) Dotter believes that only fairly large thrombı can be visualized with 6 ·Aarlo Pulmonary Veins Incomplete Gracilcahan of Leit Auncle Lert Artur DIFFERENTIAL DIAGNOSIS OF HEART DISEASE Filing Defects in Left Aurum B Puddle of Contrast Substance in Righ Venice Fic 201-B Angiocarli grapinc demon lration of thrombue in left aunele 162 Pas oli woman with miiral sirni ja auricular fibrillation and cerebral and sadidle embolu A ingegram cried 14 econds after injection in frontal and lateral pr vechione Left aurice and aorta well demon Iruted Note left auricular filling defects hown in both A an! C Re dual contrat uls tance is trapped in the apex of the right sentricle B Tracing of the angcarlingram 95 ·96 Brachiocephald Vessels Aorta Incorpere Opocification or Left Auricle Left Nrum Pulmonary Veins SYSTEMIC ARTERIAL EMBOLISM ell Ventricle 3 Filling Delect in Leit Atrium C D Contrast Substance in Right Ventricle FIG 20C D Ingibeonhngraphic demonstration of thrombus in leſt aurice C Ingiogram Note Jeft auricular filling defects B Tracing of the angiocar lugram (Reproduced by permion from Saloni Land 7aluchin The angiocardiour iphic diagno s of left atrial thromboss Circularion 11 25 1956 ) ·DIFFERENTIAL DIAGNOSIS OF HEART DISEASE Cardiac the pre-ent technic In a personal communication he wrote movement certainly is an enemy to harp visualization of mall intra cardiac ma es Should a ma s within the left auricular appendage le larve enough to be di tingur hed clearly from trabeculac carneae or irregularities in the chamber wall angiocardiography would no doulit be of con idetable value The value would vary greatly with the technic of the exaraination The horter the expo ure the more likely the diagno us for a gnen ized thrombu The longer the expo ure the larger the thrombus which might escape detection Wuh ordinary angiocardiographic technies (130 ccond or longer expo ures) the thrombus would probably have to be quarter ize or larger to be detected Other factors decreasing detail in the film would have a imlar bearing Experimental and preliminary clinical tudies indicate that radiographic etpo ure of 1 mill-econd adds gmficantly to detail and therefore the angrocardiographu yield 'The technic when per fecred may make practical the routine i ualizaron of mall mita atrial mas es Ingrocardiography has been performed after leit auricular catheter ization but major complications have occurred in a high proportion There is the probability that before many years angiocardiography may be an important adjunct in evaluating the problem of thromboembol, m in theumatic leart di ea e Unsal the Technic is perfected clinical acu men in detecting small embolt mu t remain the het procedure for identifying a left auricular throbu Subacute Bacteriol Endocarditis after Middle Age Subscule bacterial endocarditis in the middle aged and elderly wc curs mose (requer the than is generally recognized and often is un ve pected until far advanced In a combined group of 141 patients tudied in two ho pitals by Ander on and Staffurth? and by Wedgwood ? 69 patients 148 per cent) were over the ave of 40 The older the patient the fun er the time from the apparent on et to the time of recognition In a tudy of 76 patients Ander on and Stafurth found the interval was only 3 5 months for patients in the third decade in the centh decade the time interual kas 56 months in the eighth derade 10 month The delay in recognition we asribed to factor» similar to the that delay the diagnos si rheumatic heart di ea e in the middle aged fir t, a paucity of physical signs econd the yn drous nature of the ·98 SYSTEMIC ARTERIAL EMBOLISM disease (two patients had symptoms for two years), and third the failure to consider the diagnosis In five of the 14 patients over the age of 60 studied by Anderson and Staffurth the disease was not recog ruized until the second admrsion or after transfer from another hospital SUMMARY A high proportion of rheumatic heart disease is unrecognized during life Over one third of patients with rheumatic heart disease die with gross valvular deformities unrecognized Although many die with no outstanding signs or symptoms many seen in middle age are undiag nosed becau c of an incomplete examination Careful auscultation in the left lateral position and detailed roentgenologic study of the cardjar sil houette and of the mitral valses for significant calcification will identif many questionable cases Major embolism may be the first sign dis closing mitral stenosis In a patient with recognized rheumatic heart disease the probability of embolism should constantly be kept in mind Pulses in the extremities and neck should be charted and periodically rechecked, they should be examined prior to during and immediately after operation, and for 48 hours after operation, in order to detect embolism occurring while the patient 14 under anesthesia Angiocardı ography in certain instances can identify a left auricular thrombu Its status in diagnosis will be clarified in the next few years The exclusion of rheumatic heart disease makes the diagnosis of arteriosclerotic heart disease with or without hypertension relatively simple Only of rheumatic fever is seriously considered as a cau e in cvery case of supposed degeneratie heart disease will all the examina tions needed for accurate differential diagnosis be made ·8 Prophylactic Antithrombolie Measures for Systemic Arterial Embolism RHEUMATIC FEVER PROPILYLARIS again t syatem;c arterial em boli m obviously begins with preventing the cau Theumatic heart disea e or at lea tits progression to a tate favoring thromboemboli m Going further this means elimi nating the streptococcal infections that are nice to rheumatic lerer The incidence of the di e may be greatly reduced by such measures But complete elimination of it; doubtful because it a impo sble to identify and treat every case The u val practice is to treat only patients with clincally obvious streptorocral ore throats or those in whom (droal culture, reveal group A bets hemolstic treptococci but it these criteria are too strictly adhered to many rheumatogenic strepto coccal electrons soll be mia ed Streptococcı even if present, may not be disclosed except by repeated cultures done with pecial technic Posittle reſts of culture are obtained in only two thirds of pajamnts plen at the on et of theumatic lever Cluft' advocates treating every case of mud febrile pharyngitis as a Group A streptococcal infection Short of thi fir t line defence the only pro Ica) zaked of guard ang against su temic arterial embolisra is the recngnition and treatment of chronic rheumatic beart di ea e. The fir I step is to e timate the retatsverk sembols in from the type of le son and the rhythen but Whateser the e tmate actie antithrombotic treatment ordinarily is ju tified only síter the fir t secogn ed embon m Kerce the urgency 10 find evidence of elen minor emboli m Once the diagno is of embo mi e sable bed any postponement of antithrombotic treatment as umes that further enabolism will not occur or that if it does occur It will not be serious. The reported experience 18 Overwhelmingly main 1 this a symption on the contrary recurrence of embolism is hills probable and as Waschi aptis says it usually is not the first embolism that kills but one of its SUSCESSOID 99 ·100 SYSTEMIC ARTERIAL EMBOLISM Available Antithrombotic Measures The available antitlirombotic measures (TABLE 20) ve aimed at reducing one or more of the three factors in thrombosis-damage to endothelium, coagulability of the blood and circulatory stasy They must be selected so as to provide the mo t effectue combination of measures appropriate to each patient s condition 1 Conversion of auricular fibrillation to normal rhythm u ually improves cardiac output, thereby reducing congestive failure and Tanle 20–Site of Effect of Various Antithrombolic Measures in Nitral Stenosis Damaged endothelium Coagulability of blood Procedure Stagnation of blood flow Conver ton of auricular fibrillation to normal rhythm No known effect No known effect Improves blood flow Amputation of appendale Removes a portion Antithrombotic drug therapy (Dicumarol) No known cffect No effect Removes t28 nation only in appendage heduces plate no known effect ne s and pro thrombin activity let adle ive Mitral valsoplasty with appendectomy Removes a portion No known effect Correct, cau a tive ob truction stasis Improvement in these conditions will reduce the danger of Ihrom bosts but therc is no reason to expect any con iderable improiement from the restoration of normal rhythm in the left aurcle itsell since left auricular contractility is not appreciably improved by the clinge in rhythm The benefits from conversion are u ually temporary in any case since auricular fibrillation eventually returns 2 Amputation of the left puricular appendage removes only a portion of the damaged endothelium uluch is the potential ite of thrombo is Since the damaged endothelum in the body of the aurile remuns and the stagnation continues (becau e mitral stenosis is still pre ent) fur ther thrombosis is possible Removal of the appendage al o interfere ·101 PROPHYLACTIC ANTHROMBOTIG MEASURES with any ub equent operation on the mitral salse by cling the preſ erable avenue of approach As a separate procedure this operation 14 ob olete In current practice the choice of treatment is u ually made between the two mea ures yet to be di cu sed 3 Antithrombotic dru, Dicumirol) therapy operate through hu moral mecham ms by reducing not only prothrombin but al o and predominantly it main conser non factor known as PCA ( crum prothrombin consercion accelerator) or as Factor Vll proconiertın of the or rothrombopla tin 153 Dicumarol derres es the adhesivene platelet. dilat s the se el ® and tends to reduce through fibrinol 18 the thrombi alteady formed Thus it rombats both the oriminal thrombosis and al o the propagation of either the primary or the econdary red or fibrin thrombus After prolonged administra tion the drug causes deterioration of capillary integrity but it has no known effect good or bad on the damaged auricular endothelium or on auricular blood fon Wright and Foley were the fir t to demonstrate that continuous De umaral therapy could dimin h the incidence of repeated embolim in theumatic heart dlae Reports of exeral senes of prolonged application bear out the effectiveness of this treatment (Table 21) The frequency of embolum in 98 patients during 1944 months without drug treatment was compared with the frequency during 2993 months of Dicumarol treatment from the lime of the fir t clinically recognized enbolt m until Dicumarol nas acted an embolus occurred on an average of ever seven months durin. Dicumarol treatment howeser an embolus occurred only on an average of every seven years Although the reduction in death or disability from sy temic arterial embols m in rheumatic heart disea e following the continuous use of Dicumaral nece arily mu t result from a reduction in either the formation or ejection of left auricular thrombi the way this is accompli hed 15 not clear No crucial tudies of the incidence of auricular caritaty clots in treated and untreated patients with theumatic heart disease are yet lea ble Vany ingle cases of continued freedom from embol m with Dicu mari treatment hase been recorded ^3 This freedom depend of course on continued therapy It the drug 13 discontinued the patient is a ain expo ed to a high trk of death from ub equent emboli i Suck treatment nece arily imlo es nz d uemands on the physician and the patient Even with meticulous care either emboli mn or disquieting ·100 SYSTEMIC ARTERIAL EMBOLISM Available Antithrombotic Measures The available antithrombotic measures (TABLE 20) are umed al reducing one or more of the thrce factors in thrombosis-damage to endothelium, coagulability of the blood, and circulatory stası They must be selected so as to provide the most eflective combination of measures appropriate to cach patient's condition 1 Conversion of auricular fibrillation to normal rhythm usually improves cardiac output thereby reducing congc tre failure and TABLE 20—Site of Effect of Various Antithrombotic Veasures in Mitral Stenosis Procedure Damaged endothelium Coagulability of blood Stagnation ! Llood flow Improve blood flow Conver on of auricular fibrillation to normal rhythm No known ellect Mo known effect Amputation of appendage No effect Removes a portion Remove stag nation only in appendage Antithrombotic drug therapy (Dicumarol) No hnown ellect Mo known effect and pro Reduces plate let adhesre ne thrombin activity No known effect Mitral valvoplasty with appendectomy Removes a portion Corrects cau a tive ob truction atasıs Improvement in these conditions will reduce the danger of throm bosis but there is no reason to expect any considerable improvement from the restoration of normal rhythm in the left auricle itself since left auricular contractility is not appreciably improved by the change in rhythm The benefits from conversion are usually temporary in any case, since auricular fibrillation eventually returns 2 Amputation of the left auricular appendlage remoses only a portion of the damaged endothelium which is the potential site of thrombo 19 Since the damaged endothelium in the body of the auricle remain and the stagnation continues (because mitral stenosis is still pre cnt) ſur ther thrombosis is possible Removal of the appendage al o interfere ·103 PROPHYLACTIC ANTITHROMBOTIC MEASURES special maneener lor remos al of thrombs from the left auricle To present cerebral emboli m Bailey s group have occluded the innom nate and left carotid arteries during the time the auricle was being manipulated Clover laia O Reill and Janton" and other object to this procedure believing it is capable of doing more harm than good This operative precaution moreover till does not protect the rest of the body from embolism which may have serious consequences unless it is recognized early Embolism to peripheral arteries accessible to TABLE 22–Recurrence of Embolism after lural 1 alioplasty Patients with systemic arterial embolim before operation Palient with systemic arterial emboliem after operation Author Actis Dato and Morino 49 0 Glover et al 84 1 (QuestionalıI-*) Belcber and Somerville 54 4 Bordon 24 0 13 D 7 1 ("Questionable ) Bigelow and Greenwood Bland Scannell, and Myers Ellis Total 139 7 370 13 operative removal must be detected carlier by frequent determinations of the pulses Glover et al reported an incidence of only 6 per cent of surgically produced emboli m in patients with definite histories of presious embolism (o of &t palients among 452 consecutive salvo plasties! Elis 6A found the incidence 6 per cent among gronp III and 20 per cent among group IV * The reduction of embolism following recovery from the operation is Hg clinical classification of patients with mitral stenosis 19 as follows Group I A beniga group without gunficaat syroptoms Group II Patients with sotne functional impairment, uually dyeprea bat 50 propre give croup jil, P cients wih progTES ) e symptom eithr progresive dyspnea or repeated attacks of scute dyss hea of pulmonary edema Group Ty Cardiac invalids, most of whom have chronic congesti e failure.

·102 SYSTEMIC ARTERIAL EMBOLISM episodes of bleeding may occur It must be admitted that Dicumarol therapy no matter how successful, is only palliative It does nothing to relieve the underlying causes of thromboembolism 4 Combined mitral valoplasty and left auricular appendectomy cor rects the mechanical cause of stasis and al o removes an important po tential site of thrombosis Theoretically it offers the greatest benefit of any treatment for thromboembolism and furthermore it tends to relieve TABLE 21-Systemic Arterial Embolism in Patients uith Rheumatıc Heart Disease Frequency Before and During Antuhrombotic Drug Treatment Before Documaroltherapy|During Dicumarol therapy Number of patients Patient months Number of embolisms Frequency (months) Foley Wright McDevitt and Symons 29 765 77 99 1316 12 112 Owren 13 386 25 15 295 1 293 Author 14 350 21 16 406 101 Beaumont et al 14 168 50 3 3 323 5 61 28 275 103 26 625 13 48 Cosgriff Total 98 1911 276 6 9 AY 2995 35 8. Ay any actual or impending cardiac failure due to stenosis It requires no expen-lle continuous aftercare (TABLE 22) Of 370 patients with a temic arterial embolism before operation only 13 had embolism after operation The chief danger from operation upon a patient with a history of pres sous embolism is emboli m during operation cither in a vital area not amenable to embolectomy (brain) or peripheral embo lism amenable to embolectomy but not recognized early enough for a successful operation With increased experience these dangers have been lessened by appropriate measures in operative technic and by a clo er clinical observation Greater care is ob erred to as ord du lodgement of the thrombus at operation Jamison Rao and Bailey 1 3 have devised a ·105 PROPHYLACTIC ANTITHROMBOTIC MEASURES u ually are not indicated but an attempt to re tore normal rhythm ss probably justified if the teno is cau es progresie di ahtlity and if the other entern for sals opla 's are ati fied the operation hould le done primarily to relieve the inerea ung cardiac failure and spcondarils as prophylaxis again t possible thrombo 1 If there is strong rea on to suspect that emboli m 15 already occurring it may at times he adsı able to undertake the recognized rik of antithrombotic drug therapy Recognized einboli m is the prime and urgent indication for immedi ate antithrombotic drug therapy in any patient who can safely su tain prothrombın reduction After urriting an attack an untreated patient faces a 15 per cent probability of death from eventual recurrent embo lism (FtG 4) The majorits of recurrences come in the first month -one third in the fort month (FIC 5) Whether the original thromius is extruded on bloc or remains and continues to di charge embol the underlying factor that cau ed the original formation and mobilization per it and will continue to cause them Thus chronir and dangerous condition mut be oppo ed immediately and corrected permanently it so ble The choice of permanent treatment is by no means clear Although surgeons recognize that not all patient are eligible for mitral valio platy and interni ts that antithrombotic drugs are too dangerous for sorre patients there has been no crucial compari on of urgical ses va medical methods to indicate which procedure 13 preferable after the fir lepi od of embol m In an attempt to determine criteria for the selection of treatment the hories of 14 urx1yors of systemic arterial embolism have been reviened {TABJE 231l nere private patients and their cases were meticulou Is recorded The natural hretort af 14 urvivors of systemic arterial embolim muid be expected to be as follos According to the evidence about 4) per cent of all deathis should be due to recurrent systemic arterial emt als m Furthermore esentual Terurrent emboli m kould be expectel in tho thirds of the 14 and two thirds of these recurrences should od us within a year This dił not occur in the 14 udred As, deaths kese due to emboli m and rore of the four recurrences were within a year There were many imilarities in these ca es all the patients had lang tanding theumatic heart disea e mo t of them for over 20 years) with predominant mfal stenosis du but two has establı hed auricular fibrillation and of the two with normal thythm one required continuous ·104 SYSTEMIC ARTERIAL EMBOLISM nearly complete and the ri k of death at that stage is slight (TABI E 22) The general experience of surgeons is in agreement Although embo lismis per patient month before and after operation were not gnen by Glover, et alº their summary is si,nificant The fact can be aimply stated that oser a postoperative period of approximately six year in an experience of 700 cases of mitral commi surotomy, there lias been no instance (with but one very questionable and minor exception) of arterial embolism Harken reported that 108 in the first 500 patients with a 30 month follow up, there have been but 5 em boli " Sir Russell Broch 3G said the incidence of embolim after satisfactory mitral valvotomy is very amall In fact I have not had a single case of embolism occurring after operation' The results in a series of case selected for vals oplasty largely becau e of repeated embolism are significant There were no operative death in seven cases reported by Bland Scannell and Myers Although the scien patients had 30 recognized embolisms in 372 months prior to operation (one every 12 months) there was only one possible small cerebral embolism in the succeeding 70 months after operation The risk of death from emboli min a patient with a previous attack who undergoes mitral valoplasty thus is largely limited to the opera tion it elf This is about 3 per cent of the patient is in group III and 10 per cent of the patient is in group IV (About half of tho e with operative chibolism die ) If the patient is not operated upon and not given continuous antithrombotic dru, treatment the rik of death from eventual emboli-m is about 45 per cent Choice of Antithrombotic Procedure Since the risk of death and disabilits from aystemic arterial embol: m varies according to the rhythm the type of mitral valve le ion and the history of presious emboli m (TABLE 13) the treatment mut he selected by weighing the dangers against the benefits to be expected In normal rhythm with no progre sive disability the mortality from embolism is less than five per cent (T4BLF 12) Since no therapy could be expected to improve this rate the patient in the situation should merely be watched for signs of embolism In auricular fibrillation with no recognized embolism the mere presence of the arrhythmia increases the r k of death to about 10 per cent If the mitral valve is purely stenotic the ruh is nearly doubled (TABLE 12) If no embolism has been detected antithrombotic measures ·107 PROPHYLACTIC ANTITHROMBOTIC MEASURES qusardine therapy Attempts to maintain normal rhythm by quinidine theraps were succes ful for some months of years in a few cases but only in Ca e 2 was normal shythm permanently maintained Sesen had recognized embolism before conge me heart failure was clinically apparent Dicumarol therapy was instituted in every cace when embo hm was recogmized and had been maintained for a total of 406 patient months at the time this study was made Dicumarol was discontinued in orly one case becau e of headache and Tromeran was sub tituted with surcess It never became necessary lo discontinue realment because of hemorrhage in any patient During therapy there had leen four recognized embolic episodes and none were fatal Sesen patients dird of conge tive failure In even of the 14 cases mitral valvoplasty was contraindicated but continuous Dicuntarol therapy was chosen as preferable to expectant treatment. All the patients had far advanced disease and six were in congestive failure Their average age at the time of the first Tecognized embolism was 55 years and death within a few years from congealsve falute was apparently wtevitable Six died of this cave an average of three and one half years later During 126 months of continuous antithrombotic therapy there were two recognized embol ms--far less than the expected frequency-followed by recosery Although the treatment had no measurable effect on congestive heart failure it may hare prevented death from emboli m. The other seven patients also receiving antithrombotic drug therapy Here eligible for operation by all criteria except age and progreselle disability four sere aged 30 to 45 year the others w3 to 56 years Glover Janton and O Neyl} 83 among other n should be noted do not accept age par se as a contraindication to operation Congetne failure and progresente disability were present in only one of the men at the fir embolism and this was corrected and controlled (Cace B) Con gestive failures in this case however returned and the patient died five years later Two other patients subsequently developed progresive disability (Ca es 9 and 10) A case worth reporting in detail follows Case 9-Virs D F age 41 has first seen on August 6 19,1 In 1926 at the age of 16 thematic heart disease was fir t diagnosed In 1919 at the age of 39 ske Gist noticed her heart wasnt beating right This apparently was the one of alcular fibrillation 23 years aíter the recog nition of theumatic heart disease There was no restcirlion of activity She ·TABLE 23—Results in 14 Patients with Systemic Arterial Embolism Receiling Dicumarol Present status Emboli #preceding therapy Dicumarol therapy (mos) Duration of Emboli during disease (358) therapy RHDI AF 0 29 1 F 46 Age Now 53 9 Remarks Died of congestive failure ? 2 M 39 1+ 40 NSR I cereb no resid 0 Died of congestive failure 48 3 F 55 1+ 25 26 10+ Died of congestive failure 57 4152 Status at fis i recognized embolim conditions associated with mitral stenosie Auricular fibrillation congestive failure marked aortic regurgitation Normal Sinus rhythm (with quinidine) congestive failure aortic regurgitation Auricular fibrillation uncontrolled conge tuve failure Auncular fibrillation uncontrolled congestive failure Auricular fibrillation uncontrolled congestane farlure Auricular fibrillation uncontrolled congestive failure Normal sinus rhythm Total 2+ 6 0 40 3 Died of congestive failure 53 5 61 1 6 0 40 ? 61 6 F 65 1+ 23 Minor Cereb 40 > Congestive failure perests Still ineligible for operation Congestive farlare peralsts Still ineligible for operation No congestive failure Still ineligible for operation 7 M 61 67 1 17 2 NSR 65 126 8 V 45 Auricular fibrillation Auricular fibrillation 1 ? 60 31 3 0 0 12+ 4 25 50 43 10 56 11 11 53 Auricular fibrillation Auricular fibrillation +1+ 13 Djed of congestie failure Mitral valvoplasty when pro gres De disability developed Progressive disability Functional Claes II 12+ 96 9 62 66 12 53 Auricular fibrillation 2 41 0 1 prob after 5 yrs I after 3 yrs 0 1+ Functional Class II 58 13 11 30 IV 11 Auncular hbnllation Auricular fbrillation 2 2 یہ اب 23 10 4+ 0 26 Lost to follow up Lost to follow up 32 46 Total 280 ·PROPHYLACTIC ANTITHROMBOTIC MEASURES probally the cause of them. Duning the pat no year the patient has suffered s resal tras tary episodes of upropskou ness and numbnesa un bon and weaknes of the rikt arm, interprete i as minor cesel ral embols Trorgegan therapy has been in tute! with no headaches resulting and no further embolia Honever the patient fse incrta ing y pred na effort and the nk of urgery » prcsier at hier pre-ent ast 62 Yeart In 200 morths of continuous Dicumirol therapy of the pas en patient eligible for salopla ty there were only to embolic episode- an average of one esery Il year Fyen for the to patients (Cases II and 12) suth treatment totaling over 12 year the frequency of embolim is much lower than it was before treatment and progrete di 31111111 has not occurred de pite the unfasoyable prognosi u ually a ociatri with emboli m and fibrillation Cas 11-53 vear old man wa du able with monoplegia Ir the fir erabilt m (cerebral) During the next five vears he had reprael embuli en In the spleen mesentery and kidness wluch sequire mi k praluatinr From the a e of 38 (January 1918) he was treated continuou ly mit Dcurant and bad no further clinical embols is seven years le chil sbrie was one esidence of a mesenteric embalm much left n noticeabl cquels He has taken Bicumarol continuously T Dype er 12 year Case 11- 5 rear old woman was first seen after having had tu mbolism fone cerebral) in the previous Iwo years After 37 mintha Drcumarol therapy another cerebral embols m occursed It is debatable whriber the seven patients ehgible for mitral valvplats muld have fared befter had operation bera performed earl but in retro pert it seems that they would hale Although progresse ability was not pre-ent at $1 ut developed later in three palier Cares or 10: One of these patient Les (Case) another has und gore surce ful salseplasty (Ca e" and the third is now oser a refuses to con id r an operation Cace 101 While no astficant ability has ocurred in sasel end 1. after years of Dicumaroi theras till thi cuur e has required vigilance has been rypen ise for the trest and ha \ een overca i by the con tant po abilities of patholo, I treding and al further embolica Tk ondition of the patient in case Il at age 6 y amazmg We ) progres ne dy pres is able to walk without difficulty and has mpt ms of Beginning cardiac faylute It 13 behly indicative of in. We po ibile in certain patients with rheumatic heart di ease na embol mix curs Fmbolzen has orcusted once each in case 11 ·108 SYSTEMIC ARTERIAL EMBOLISM said she was able to run up tairs without shortness of breath in Varch 1950 she developed pain in the leg sluch was diagno ed as an arterial embolus She was hospitalized for two weeks In April of 1930 she had lower abdominal pain anorexia and vomiting which were interpreted a me enteric arterial embolism Following this epi ode alie still suffered no limitation of phy ical activity In August 1951 following pain in the left upper quadrant a palpable spleen was noted Documarol was then given and the treatment maintained for 29 months with no recurrence of embolim A dosage of 375 mg of Dicumarol daily maintained the prothrombin activity between 15 and 35 per cent In the last six months of 1993 in of increasing di ability appeared She noticed sliorinesy of breath and easy fatigability which had not been present prior to then Examination of the heart liad always indicated predominating mitral stenosis A low pitched diastolic murmur was heard at the aper with no evidence of mitral regurgitation The roentgenogram of her che i revealed a moderate accentuation of vascular markings suggestive of minimal pas ne congestion The cardiac silhouette showed a rather marked prominence of the pulmonary conus area The right anterior oblique view showed moderate prominence in the area of the left auricle The finding therefore were those of apparently pure mitral tenosis with euidence of left auricular enlargement left auricular failure and symptoms of undue dy apnea and easy fatigability She apparently was a satı factory candidate for mitral valvo plasty Dicuniarol was discontinued for two weeks before operation She was operated upon on January 14 1931 by Dr John C Jones Operatie Mote The pulmonary artery was large and ten e The auricular appendage was small and contracted It contained both friable and black clot in addition to organized carred old clot and the opening into the auricle was extremely small The body of the auricle was large and no clot was felt therein The anterior valse leaflet was calcified with a plaque of calcium about 14 inch thick The opening in the mitral valle itself w38 less than 1 cm in diameter There was no regurgitation either before or after finger fracture The remaining opening at the end of the operation was between 34 inch and 1 inch long Since the operation the patient has had no euidence of further embolism and has been changed from a functional classification III into cla » II The auricular fibrillation was rei crted hi qumadine lout the dose required for maintenance was infea ible and auricular fibrilla tion was accepted as an establi hed rhythm Another case worth reporting is that of a woman who had a minor cerebral embol, mat the age of 56 Case 10—The patient was given continuous Dicumarol therapy for sit months but persistent headaches deseloped apparently an cracerbation of a migraine tendency that had appeared earlier in her life Since the headaches did not recur after discontinuance of Dieumarol the drug was ·PROPHYLACTIC ANTITHROMBOTIC MEASURES auricular fibrillation survie to normal erpectancy with only minimal disability ti the thromboembolie mechanism does stat occur ARTERIOSCLEROTIC HEART DISEASE It would be unwi e to exclude the future po sibilty of operalne remo al of necrotic myocardial ateas predi posing to thrombo 14 The exci ion of sentricular aneury ms in selected cases already has been achieved " The indications for each procedures and the neces ary pues fections of technic mu t be relegated to the future Incrra ing experience in the use of antithrombotic drugs in arteriosclerotic heart di pace honen er 18 leadily cry tallızıng opinion regarding indications for their ute Wherea the use of Du umarol in Theumatic heart disease seems ju h fied only to prevent the recurrence of emboli m alter it has already been recognized it is indicated in arteriosclerotic heart di ca e as soon as tho e conditions occur which most often give rise to a primary thromb«* The danger of thrombo is in rheumatic heart disease cannot be imilarly limited to a tort period in arterio rlerotic heart di ease it is greatest immediately follos ing myorardial infarction and in any period of congestive heart failure Effect of Dicumarol on Formation of Yentricular Mural Thrombi In everal necropsy serie the effect of Dicumarol on formation of ventricular mural thrombi has been compared with findings in untreated patients These tudies reflect the resuls obtained in practice and reveal a wide variety of conficting conclucions tur that the mificant effert of Dicumarol is an oppo ing the mobili zation rather than the formation of thrombi Burchell 38 quoting results he obtained with VicQuay and Edwards (unpublished data) found as many mural thrombi following mocardial infarction in patients who had been treated with Dirumarol as in the e who had not but of the 16 treated patients with mural thrombı none had gro s sy temic embol at necropsy It the same cline in 33 per cent of 83 untreated ca es of acute myocardial infarction with left sided mural thrombi evidence of Stateini arterial occlu 1or kes found at Decrops, Second that the efferi v raider in inhibitin, clot formation the reduc fon achieved about 50 per cent Honell and hyser 119 contracted the findings in 31 palients dying of my carlial infarction and relening 17 ·110 SYSTEMIC ARTERIAL EMBOLISM 12 and in addition these patients face the inevitable con equences of congestne heart failure at which time the opportunity for ucce sful operation will have passed It would appear then that mitral valoplasty cannot be ruled out of consideration merely because of the added risk imposed by old age or because the absence of progressive disability makes the operation less urgent These 14 cases illustrate the indiuidualization necessary in determining proper treatment A tentative program ba ed on the available evidence is as follows Patients with rheumatic heart dı ease and auricular fibrillation are regarded as the most likely (four to one) to have systemic arterial embolism When angiocardiographic technic for visualization of thrombi is improved these patients will be the ones to be considered for study by that method The recognition of systemic arterial embolism is considered to de mand that immediate Dicumarol prophyla us against recurrence (unless contraindicated) be continued until the most suitable future treatment can be selected Mitral valvoplasty is preferred to lifelong antithrombotic drug therapy, and progessive disability is not considered an indis pensable criterion Embolism alone is an adequate reason for operation Tor the patient eligible for valvoplasty, drug therapy not only is onerous and expensive but merely postpones the time when operation will be necessary When that time comes the patient s age will have increased the risk of operation perhaps so far as to make it unjustifiable The danger of death or disability from subsequent embolism must be meas ured against the danger of operatie death or of disability from an embolus during operation The mortality from eventual recurrent embolism can be estimated at 45 per cent whereas the mortality at operation is now about five per cent Ellis og has shown that the rik of an embolus during operation on a patient with previous embolism in Group III is only five per cent but in (roup IV 20 per cent This is an added reason for early operation However if operation is contra indicated drug therapy should be continued for lıfe provided the necessary conditions can be reasonably assured If fibrillation is pre ent an attempt should be made to change the rhythm to normal and main tain it. Only when circumstances forbid either operation or continuous drug therapy should expectant treatment be resorted to If systemic arterial embolism has not occurred in theumatic mitral stenosis it is justifiable to await the progression of disability before recommending operation Many patients with cardiac enlargement and ·113 PROPHYLACTIC ANTITHROMBOTIC MEASURES thrombų in 63 per cent of 133 patients without anticoagulant trialment who survived more than three days and in 78 per cent of 23 patients who were gren antu pagulant drog more than threl days after the on et Among 51 patients to whom anticoagulants were given prior to the third day however only 15 per cent had mural thrombi-sig nificant reduction--empla izing the need to begin Dicumarol prophylaxi within three days of the onset of 323 ocassial infarction It is apparent that in myocardial infarction Dieuin stol 24 gnen clinically presents the formalion of sentricular thrombi in only 50 per cent of patirnt at best Either thu u ual prothrombin reduction 14 not ulicient to prevent formation of thrombus in half of the patients or an adequate level is not continuou ly maintained VcQuay Burchell and Edwards1 believed they had maintained the acrepled effective prothrombin reduction in all but 10 per cent of their patient and Howell and hs er 119 reported mural thrombs in four of 15 padenle whose protrombin activity had been maintained bencen 20 and 30 per cent Althou, h none of these fussen eparated the good ok from fad n cases there can he little doubt that the probability of Irit sentric ular thrombosis is much greater in patients with large tran mural infarcts and congestae falute In a sing the value of Dicumarol howeser necesary to con ider not merely its lifesaving value or its inhibition of mural throm b> hut on its total antithrombotic effect and in addition niher po sily valuable properties not selaled to prothrombın reduction Prophylactic Use of Dicumarol in Acute Myocardial infarction The efficacy of Dieumarol in reducing mortality and thromboembo Is m in properly elected ca ts of acute myocardial infarction > gen prally accepted At the International Conference on Thrombo is and Fml olism at Basel in 1934 the opin on was vnanimou that aplica agulant drugs hould be guien to every patient with acute myocardial mfarction unle s there were contraindication This ym 19 oppo-ed honeser by Rus ek et al 15 16 ho would fumit Drumarol prophylaxis to about 30 per cent of all cases by exclud ing mild or good atk ca es from tealment They base their dis ent in their e limate of the su k of Drumarol therapy (which they consider exceusise in compari on to the danger of mild myocardial infarction) and on a contention that these milder cases can be reliably identified ·112 SYSTEMIC ARTERIAL EMBOLISM Dıcumarol with tho e in 98 untreated patient. The frequency of mural thrombı in tho c recching prophylactic treatment was 30 per cent !! the untreated 51 per cent These nuthors considered the control of thrombosis, as determined by prothrombin actnuty to be good in 15 pitients fair in 9 and poor in 10 Surpri ingly there wa Hitle difference between the e treated groups (good, fur and poor) in the actual incidence of mural tlırombı but the difference between the treated and the untreated according to chi square analys was alati tically sig nificant in another series of 121 patients dying of acute coronary arterial occlusion without antithrombotic drug treatment Rissanc, Fidler and Conn 131 found murul thromb in 48 per cent while among 191 receiving antithrombotic drugs they found mural thrombi in only 26 per cent Although the c authors did not corrclate the incidence of mural thrombi with the degree of reduction of prothrombın acuity they concluded that the incidence was significantly reduced by the drug In a similar study Wright Marple and Beck O found mural thrombı in 63 per cent of 18 untreated patients but in only 32 per cent of 41 who lind recchi ed Dicumarol Among 75 untreated patients Glucch, Ryder and was crman " found 41 per cent with murul thromba as against 23 per cent of 56 ndequately treated patients ( adequate range was 30 per cent or less) Third that in fatal myocardial infarction the drug does not cru ca aig nificant reduction in the midence of ventricular casitary thrombı or of peripheral infarction (presumptive cudence of embolic occlusion / Gilchri t and Tulloch s found that of 139 untreated patients 56 (10 per cunt) who died later than 24 hours after the attach of niyocardul infarction had ventricular mural thrombı Of 80 treated patients dy mg more than 24 hours after the atta (33 per cent had ventricular mural thrombı The incidence of peripheral infarction in the untreated patients was 21 per cent and among the treated was 15 per cent The e figures in regard both to thrombo is and to peripheral infarction were considered suggestive but not stati trally ignificant The e nuthor did find however a pronounced and lughly significant reduction in the incidence of pulmonary infarction in the trented but fatal caso 34 per cent (3) in 88 treated ca es and 17 per cent (27) in 160 con trol autopies Fourth that the drug does not cause i Jonificant reduction of ventric ular mural thrombi unlean given within three days after the clinical on il of myocardial infarction Les and O Neal 119 demon trated mural ·115 PROPHYLACTIC ANTITHROMBONC MEASURES will fail to bring out that high incidence of thromboembol m wluck can be detected by active search according to previou ly defined criteria In another controlled tudy Furman et al er found no significant difference either in mortality or in thromboemboli m between 50 Drcumarol treated and 76 untreated good risk patients Button 1 hox mer did find uch a difference in 156 good rh patients receiving Dicumarol of whom 2 per cent died and 6 per cent had thromboembo lism in contrast to 5 per cent mortality and 11 5 per cent incidence of thromboemboli m among 58 control patients As Gilchrist and Tulloch * observe If it can be verified that 3 in 100 good r patients can in fact be saved who would otherwise be expected to dic and the incidence of thrombotic complications halved thanks to the use of these drugs then anticoagulants would appear ju tified so far as the family amul the individual wage einer are concerned The late result of contin9owDicumarol prophylaxis for mild casem have not been well established Suzman Ru ki and Goldberg " found no reduction in late mortality among 15 surviving good nih patients receiving Dicumarol up to 76 months after the onset of acule mio cardial infarction but heyes Drake and Janney Smith 138 though they did not separate their good ni k patients did note a prolound reduction 232 mortalsty four years after the attack in 7 patients with a single infarct who received Drumarol, with a mortably tart of 8 per cent against a rate of 47 per cent in 186 comparable untreated control patients Danger of Dicumorol Therapy in Myocardial Intarchon Ruasek 19 bases his contention that the drug is more dangerous than the ds ease upon Unghis e timate that Dicumarol therapy contributes to the death of 17 per cent of patients so frealed But while Rush maintains in the face of considerable di agreement) that if possible to distingui a reliably between goo Ilk and bad r k ca es oon after orset. he applies this estimated death rate to the good nik ca es al though it was dernied from a tudy of myocardial infarction in alt degrees of severity It cannot sea onably be etpected that fałał compli rations due to Bicumarol »ould be as frequent in mild or good rik cases as a cerere cases with a high s k Wingkt Varple and Beck 16 made a controlled tudy o uch good rik cases (adhering to Ru seks eriteria) in which they found 34 instances of bleeding in 114 Dicumarol treated papients and ange in ·SYSTEMIC ARTERIAL EMBOLISM soon after onset Russel 99 concludes that the use of the drug in "good rik cases is costly, burden one, and unnece cary Schnur 14 too objects to the expense inconvenience, and danger of Dicumarol prophylaxis as well as a unisersal difficulty in maintaining constantly effectic concentration in the blood In mild cases he contend onls one death in one hundred is theoretically preventable by Dicumarol prophylaxis One life in one hundred of course, is well worth saving and the effort should be made unles it can be dernonstrated that the drug is more dangerous than the disea e Value of Dicumarol in Good Risk Cases Since the value of Dicunarol in more severe ca es of myocardial infarction is generally admitted attention can be turned on the contro versial good risk case Russek considers good risk patients as tho e without (1) a history of previous myocardial infarction (2) intractable pain, (3) extremne degree or persi tence of shock (4) significant enlargement of the heirt (5) gallop rhythm (6) congestive heart farlure (7) auricular fibrillation or flutter sentricular tachycardı? or intraventricular block and (8) diabetic acidosis or other states pre disposing to thrombo is The immediate mortality rate in untreated mild ca es is so low that neither beneficial nor detrimental effects of Dicum rol can be demon strated without a careful studs of a large serica Sunce a double blind test is not feasible,"4 the best available method is to treat alternate good risk patients and conipare the mortality rate and the thromboembolic complications with those for the untreated good ok patients The has been done by the American Heart As ociations Conimittee on Anticoagulants Wright Marple and Beck o reporting for this com mittee found no significant difference between the immediate mortalıts rates for 114 Dicumirol treated patients (18 per cent) and for 65 control patients (1 5 per cent) On the other hand they found thrombo embolic complications in more than 20 per cent of untreated patient, against nine per cent in tho e treated They emphasize that presention of death is not the only objective of treatment and that a rea onable Tiek may be taken to prevent cuch nonfatal complications as cerrlyra) and peripheral arterial embolism pulmonary emboli m and recurrent infarction They note, too that Russeh found thromboembolic compli cations in only three per cent of untrealed good risk case but they feet that a retrospective study like his limited to reviewing ho pital record ·117 PROPHYLACTIC ANTITHROMBOTIC MEASURES can le maintained safely in patients having muld aitacke it 13 lughly de sable The number of patients having muld all ichs (without treal ment) who develop serious thromboembolic episodes 13 a convincing bit of evidence fasoring treatment The dangers of bleedmg are over empha ized Bleeding complications which occurred in suppo edly Lilled hands over five years ago when physicians had lens experience would not occur today When contraindications to the use of Dicumarol are li ted the em phasis is u ually placed on the presence of lesions that might predi po e to bleeding but this i not the mot important contraindication Job ably more important is the inexperience of the phy ician and pert the lack of reliable laboratory control Ru ek singi tence that consideralion should be given to the probabile results of therapy adınım tered in maller ho pitals or in the patients homes under the guidance of les skilled hande is well taken The proper admisi tration of Drumarol with afety requires a lughly hillal technic It is not to be undertaken by an un hilled physcian in cither a small or large ha pital with questionable laboratory facilities nor usually to be tarted in the home The admitted madu aluilty pl usong the drug under uch unde irable circum tances however can in no way negate the adu ability of the use of the drug under proper condition The us of any procedure requiring pecial equipment indicated only un der uitable conditions The recommendation of the Committee on Anticoaulant of the American lipart te ociation in its initial report in 191 till rems ju tihed Anticoagulant therapy Itald le u ed in all case of coronary thrombosis with myncardial infarction toolen a definite contraindicalycn eri la CONGESTIVE HEART FAILURE 16 Dicumarol can be given afely a the evidence esta s hould Te administered for congestive heart fasure Significant reducion in thromboem . m ha been recorded in treated patients and contra fed to untreated control patients by a number of inir ligatore ps 110 Grillith et al! frund improvement in all types of heart di ease care ir pulny sale and luclic heart disea e noestise heart failure contrsbutes 10 the farination of peripheral nous thrombost and pulmonary embolism in rheumatic heart do ease and to the formation of leit Sentricular thrombi in arterio clerotic heart ·116 SYSTEMIC ARTERIAL EMBOLISM the 65 untreated control patient of the 14 in tances of bleeding how ever, only one as severe and was due they believed, to obylous cire le s management " The patients prothrombin time had been 56 second or longer for a wech, and over 60 seconds for three days, he was then gnen another 110 mg of Dicumarol There was no contraindication to the uue of the drug except the most imį ortant contraindication of all the incompetence of the attending physician Nevertheless the patient recovered from the hemorrhage The pres ulimiy picture of Dicumurol therapy for acute myocardial infarction is far removed from such mishap With increa ing experi ence the incidence of death from hemorrhage is steadily decrea ing especially in good rica es in competent hands Regardmg acute myocardial infarction specifically compilation of 15 series, covering 1572 treated ca es, indicates sesere bleeding in 07 per cent ill patients) will hemorrhage contributing to death in 03 per cent Burchell ? points out that in low rish case the dangers of anticoagulant therapy are minimal control 19 most rendily achied and the poasibility of salvage is greatest We are willing in gnc antı coagulant therapy 10 one hundred or more patients with the hope of preventing one death he declarts It can be coneluded then that just as the greater risk of lienzor lingic death is worth taking in erere myocardial infarction o the slighter nk is justified in mild good risk ca rs In a good niherr if the prognosis is cicntually found to be correct the patient will have been protected both aguinst fatal acculent and al o against erious (though nonfatal) thromboemboliem De Francisco and Tright lisic reported] 11 instances of either serious or fatal thromboembolism in 11 initially mild ca es II on the other hand the infarction is more excre than fir t beleid (Halpern Lemberg Belle and Eichert 107 found it neces cry to ruuse their evaluation in one third of 107 (?ses) the patient will have had the benefit of Documarol therapy during the crucial first three days when it is most effectue If Dicumarol therapy is denied in supposedly good rik ca e it us!! loc denied al 13 tho ceaves afire the di ease originally scems to be le (tere than it really is Program of Treatment for Good Risk Patients In the ab ence of conclusive evidence (whuch cannot well be forth coming since loulile blind tests are infen able) the we play avc1111 must depend on general principles ſi reduced coagulability of the blood ·9 Continuous Antithrombotic Drug Therapy in Heart Disease ARTI RIAL FVBOLIZATIO! in patients with Theumatic heart diese and recurrent myocardial infarction both are becoming accepted by man) physicians as reasonable indicanons for continuous antithronsbolic drug treatment further experience ugge is that patients with severe firt attacks of myocardial infarction can be benefited by long term treat ment.13Chronic conge tae heart failure is another probable indication although Friedberg s admits that the difficulty of consencing many phy sciany of theu (anticoagulaut.) value in miocardial infarction de pile impressive tata trcal endence in their fasor suggests that it will be even more diffil ult to obtain convincing evidence of their benefit in heart failure The abihty of Dicumarol to reduce prothrombin activity and inhibit entrasascular coagulability is unde puted In era when so mans dealhs are caused by clots forming in blood ve sels during hile the availability of a drug which can dımını h this tendency to thrombosis is a clinical god end If safe a continuing reduction in coagulability would be desirable in every per on in whom the dangers of potential thrombo is are continuously present Frperience continues to demonstrate that uch prolonged therapy i properly controlled us as ale as hort term therapy It is feasible com patible with an actise ble and with travel and requires only reasonable pret auton This attitude mark, a dynamic turning point in the manage ment of previou ), du couraging thromboembolic di rar or as Tulloch and right - 1 tate a change from a tane and resigned approach in which patient and physcian alike awarded with apprehension the posibility of a cries of serious or even fatal development In no other cardiovascular disorder is Dictimaro o effective as in the reduc tron of recurrent embohem in theamatic utral stenosis Although its chief mode of action is not known--whether it presents the formation pe spa at n or mobihzation of left auricular thromb there should be little doubt that the de ired end result the prevention of recurrent * termic arterial emboli m is achieved ·118 SYSTEMIC ARTERIAL EMBOLISM disease It increases the incidence of thrombosis in diseased arteries in both dıeases Jordan, et al 13 demonstrated the increased incidence of left ventricular thrombi in arteriosclerotic heart di ea e a sociated with congestive failure Prophylactic Dicumarol treatment is indicated for congestive heart failure resulting from degenerative heart disease from any cau e SUMMARY Three measures are available to reduce the recurrence of left auricular thrombosis in rheumatic heart disease drug (Dicumarol) therapy to lower the coagulability of the blood as far as the danger of hemor Thage will permit combined mitral valvoplasty and left auricular appen dectomy to correct the mechanical cause of stasis and to remove an important potential site of thrombosis (auricular appendectomy is no longer done as an isolated procedure) and conver son of auricular fibrillation to normal rhythm to improve cardiac output and dımınısh mtasi Upon recognition of systemic arterial embolism Dicumarol prophy laxis should begin immediately unless positively contraindicated Pa trents eligible for mitral valvopla ty may well submit to operation even before progressive disability makes the operation more urgent and the condition lens favorable If operation is contraindicated or refu ed liſe time antithrombotic drug therapy should be maintained if fea şble If the auricle is fibrillating normal rhythm should be restored and main tarned if possible It is generally accepted that the risk of hemorrhage in severe acute myo cardial infarction is well justified by the salvage obtained with prompt and adequate Dicumarol prophylaxis directed toward preventing throm bosis both in the left ventricle and in peripheral vessels In milder ca es however the less demonstrable benefit of Dicumarol still justifies the slighter risk and insures against the graver risk in those cases (perhaps as many as one third) where the disease unpredictabls becomes worse Dicumarol is indicated on the appearance of congestie failure enther in rheumatic heart disease in which this complication predominantly increases the tendency toward venous thrombo is or in arteriosclerotic heart disease in which in addition it promotes left sentricular and arterial thrombosis ·CONTINUOUS ANTITHROMBOTIC DRUG THERAPY had died (FIG 211 In the mild cases the authors found no significant reduction to ju tify continuing therapy beyond the acule pha e Kezes Drake and Janne Smith 239 gare Dicumarol continuou ly to one group of patients who had single infarcts and continuing anginal ymptoms and to another group with multiple infarct comparing the result in those groups with results in two milar groups wlio had recened no Dicumarol during or after the attack they found that four years after the ingle infarction 41 per cent of the untreated patients WETE dead but only º per cent of the Dicumarol treated had died Among tho e with recurrent infarction 63 per cent of the untreated died within four years of the first attack compared to only 12 per cent of the Documarol treated patients. These findings suggest that even after an mitallo mld attack the patient with coris19g anginal my toms will benefit from long term theraps FACTORS AFFECTING DICUMAROL THERAPY Succe fal continuous treatment with Dicumarol hinges on the relia bility of the patient the physcian and the laborator Plysciun« er Tenenced with this drug learn to apply inc crima in determmung the eligibility of all thret parties but many others without uch cyper ener imply hun the drug entirely because of an unwarranted fear of induting hemorrhage The danger of bleeding varies with the condition treatech Fath Jlogic hemorrhage is les frequent in rheumatic brart divathan in ather thrombotic conditions for becau e the vounger patients u ualls have fewer potential nes of erious bleeding and second becau e it is not nece sar; do greatly reduce prothrombin activity in order to control the thromboembolic tendency In addition theses the re3 urante in every care of reduced prothrombin aclıtt's that the vitamin A, preparations can rapidly restore normal coagula bibly The e fartors as ure greater afety in 4 Ing Dic umarol permit its application to a larger number of patient and ju lify a longer interval between laboratory te is Besond this imple outline there are inesitable complications which unle s under toed will cause the theraly to be condemned Many phi kian are t»!} puzzled by the fact that within the ame supposedly protecine range of prothrombin actuts thromboemboliem may ocur at one time and bemonha e at another However most vascular disease present the ame dilemma--the ·120 SYSTEMIC ARTERIAL EMBOLISM Selected patients who survive acute myocardial infarction Ine longer and have fewer recurrences with continuous Dicumarol therapy Three causes of death await two thirds of the survisors of acute myocardial infarction, according to Achor et al 1 Tliese are conge tre heart fa lure recurrent myocardial infarction and sudden death without conge tre failure or acute infarction In 21 (8 per cent) of 250 patient systemic DURATION OF OBSERVATION AND MORTALITY NOS OF CASES LONG TERM SHORT TERM 82 CASES 88 GASES 201 15. 10 3H D DEATHS 1 2 3 4 5 6 7 1 2 3 4 5 6 7 YEARS YEARS FIG 21 Mortality rate among patients with myocardial infarction given Dicumarol only during acute attack and tho e gnen it continuou ly (By permi sion from Suzman VI M Ru hin HD and Goldberg B in evaluation of the effect of continuous long term anticoagulant therapy on the prognosis of myocardial infarction A report of 82 ca e Circulation 12 338 1935 ) arterial occlusion (thrombotic or embolic) was a major cau e of death Dicumarol could be expected to lc beneficul in conge tre heurt failure and to reduce the incidence of recurrent infarction and av temic arterial occlusion The antithrombotic action plus the pre umed 120duators effect could reduce the incidence of sudden death Suzman et al"! have compared the mortality rate in two groups patients surviving acute myocardial infarction One group of 88 recensed Dicumarol only during the acute plia e the other 82 recensed at both in the acute phase and continuou ly thercaſter (FIC 21) Before the end of the fourth year, 27 (33 per cent) of those on short term therapy were dead but only six (7 per cent) of those on long term therapy ·123 CONTINUOUS ANTITHROMBOTIC DRUG THERAPY against thromboemboh m and bleeding Either complication or both of them together may occur in certain instances Tulloch and Vnght reported thromboembolism occurring during Dicumarol therapy in 13 patients whose prothrombin time indicated a supposedly adequate range (23 to 40 cecond 20 and 10 per cent of normal) and even in three patients who e prothrombin time has longer than 40 econds (below 10 per cent) in all cases of bleeding uchel lvy Barber 1 prothrombin arinity was in the called therapeutic range 77 (10 to 30 per cent) Foley Wright Me Devitt and Symons report in tances of bleeding in 85 patients receiving long term antithrombotic dru, therapy for various conditions in which the prothrombin time was within therapeutic range in appen and further investigation in these ca es revealed pathologic conditions eg hemorrhoid gyneco Ingical disorder and renal calculi in four imilar ca rs studied by Owren " the causes of bleeding were renal calculye renal tuberculoare bronchietasys and gastric ulrer Un u pected catcinomas of the bowel ir the uterus and ulcers of the bladder and the duodenum have been dr closed by bleeding occurring at ordinarily desirable levels of pro thrombin activity *** These findings indicate that the lesion and nat the prothrombin level determines the onset of hemorrhage The level at which bleeding is induced in this lesion determines the ale kiel mce it is impo sible to detect much less evaluate every potentially hem arrhagic lesion in the body the nk cannot be mea ured ercept taf tically The supposed therapeutic range can only be a compromise low enough to prevert clotting and high enough to prevent bleeding to most in tances If prothrombin activity were further reduced throm boss would be lens probable but the danger of bleeding would become prohibuie l the reduction were lighter bleeding would be less of a danger but the r k of thrombosis would be greater Danger of Bleeding (Minor and Major) Vinos bleeding of a degree neither fatal nor disabling frequenily occurs with prothrombin activity in the therapeutic range At accessible sites as in epi taus oozing from the gums or areas of purpurs ! can ordinarily be ignored (if blood dy crasızs are excluded) since it not refect the pre ence of potential bleeding lesions elsewhere not augur future serious bleeding Such bleeding probably results from a localved capillary delect and any II k at CBISies is far mulweighed by the ni k of disability or death from thromboembolic complications de ·122 SYSTEMIC ARTERIAL EMBOLISM danger of thrombosis from damage to the intima at one site, and of bleeding from a break through the adsentit11 at another Corre pond ingly, there are not one but tio important lesels of prothrombin reduc tion the effecte lezel at which thromboembolism in presented and the safe leiel, below which serious bleeding may occur cither of the c levels is predictable in any one patient The effective level varies wath the type and particular stage of vascular damage In Buerger's disease and blue phlebitis (phlegmasia cerul a dolens), for example the risk of thrombosis is high - in acute rlieu matic arteritis and auriculitis it is low, with nornal cardiova cular endothelium thrombosis cannot occur While prothrombin activity in Buerger - discase might have to be reduced to 10 per cent of normal or loner to present thrombosis in rheumatic arteritis a moderate reduction to 50 per cent might pos ibly be sufficient to prevent thrombosis In the acutely necrotic tage of myocardial infarction, the tendency for cauitary thrombo in i great and a reduction below 20 per cent initialls might lie necessary however as the endocardium heals, the thrombotic tendency le ens until of complete healing takes place and normal endothelium covers the area no thrombosis will occur at that site even with normal prothrombin actuty The safe level e individually determined but cannot be individually predicted It depends on the nature and state of the vessel wall of the whole vascular tree In the normal blood secl there is no tendency toward either bleeding or thrombosis Quich 19 asuurca us that when the vascular syatem is intact there will be no hemorrhage cien when the blood is incoagulable from any cause lack of thrombopla tinogen (as in hemophilia) prothrombin deficiency heparınızation or total absence of fibrinogen “Hemorrhage occurs fie state only when an adılıtional factor is superimpo ed on the original coagulation dcfect (Italics are mine) Similarly no bleeding occurs with the coagulation defect produced in man by Dicumarol if the Ice el alls are intact Clinically bleeding occurs because of the c additional factor Lesions such as a peptic ulcer or a cerebral aneurysm although not bleed ing with a normal prothrombin activity will begin at possibly an 80 per cent or 50 per cent lesel or po sibly only of the activity is reduced below 10 per cent To be safe prothrombin levels mu t stay above the figures an impossibility in all cases since these figures are unpredictable Any arbitrary range of prothrombın values cannot alway“ protect ·125 CONTINUOUS ANTITHROMBOTIC DRUG THERAPY cardial infarction concluding A mile anticoagulant protection 1 definitely better than none Griffith et al 10 found that among patients with congestive heart failure who e prothrombin activity was maintained below 6 per cent only 18 per cent had thromboembolism (all types) while among those with Su hter redurtion the frequency was 15 per cent The e authors suoge ted to per cent of normal as the safe prophylactic maximum Brambel Hunter and Fitzpatrick 33 ale helsere that between 45 and 50 per cent is a protect se reduction Burt' tated that her aim was to keep the prothrombin level between 30 and 60 per cent With regard to chronic rheumatic heart di ea e there is no controlled tudy to how that the formation of left aurirular thrombs 1 presented The only practical control in evaluation of this therapy is the patient previous history compared with his course following treatment (T48LF 21) The evidence o obtained that Dicumarol does reduce the incidence of emboli m by only a moderate reduction of prothrombin activity is convincing Regulating therapy by the prothrombın and proconvertin te t Owren 154 had only one recurrence in 13 patiente maintained for 29) patient months at 10 10 30 per cent level Smih and Schelling point out that the e apparently low levels actually corres pond however to 39-44 per cent and 57-58 per cent in terms of the fuck te 1 (FIC 22) This indicates then the efficacy of only a moderate reduction of prothrombin actists Cosgriff maintained in general a range between 15 and 30 per cent of normal prothrombin activity Wood and Conn & maintained prothrombin activity at 20 10 35 per cent of normal My experience and that of my associales in treating 301 private pa tients with chronic kardiosa cular discase for periods ranging from three months to nine years has led to the conclusion that in ambulatory patient a reduction in prothrombin actisity to 50 per cent 19 satisfactors TREATMENT FOLLOWING ACUTE EMBOLIC OCCLUSION The detailed treatment of acute embolic arterial occlusion of the extremities i leyond the scope of this monograph and 15 well descuid in everal recent frytbooks Frequently not eses the best treatment can avert occa ional lo , of hfe and limb The contnbution of surgery to relief of emboli m is limited to indications of relatively infrequent occurrence For aortic gaddle eraboli m 25 An example surgery has ·124 SYSTEMIC ARTERIAL EMBOLISM of the diseases for which Dicumarol is indicated The wae dictum of Olwin and Friedman 181 should always be considered in treatment 'A little bleeding may be of light con equence, but a little clotting may mean the difference between a living and a dead patient The only risk that deserves detailed consideration is serious bleeding Bleeding is serious only when it occurs at a site where immediate vital or irreparable damage is done by a small hemorrhage (as in the brain) or at an inaccessible site where a massive lo s can cause death before it can be halted by administration of vitamın hs, or replaced by transfusion Fatal bleeding has nearly always been froni a cerebral artery during treatment for atherosclerosis not for rheumatic heart di ease Among 1334 caves of cardiovascular disease treated by Beau mont and Tarrit 19 with esther Tromexan or phens lindanedione fire deaths occurred, all among athero-clerotic patients and all due to cere bral hemorrhage Three of the patients were being treated for cerebral thrombosis and two for hypertensive cardiovascular disea e of the sxx patients with cerebral hemorrhage tone was not fatal) two had at least 30 per cent of normal prothrombin activity and one had 10 per cent In contrast to this incidence of serious blceding there were no deaths among 450 patients treated by the same authors for valvular heart disease Luckey 1 s believes that nearly all cerebral hemorrhage re ulting from treatment can be avoided if the drug is not given in two conditions during the pre ence of a blood pressure above 160/90 and during the presence of xanthochromia or red cells in the spinal fluid le comment ruefully however that a very small proportion of our patient with cerebral vascular accidents have neither hy pertension or xanthochromia The comparative freedom from serious bleeding among patients with rheumatic heart disease is borne out in other studies probably becau e the danger of cerebral hemorrhage is le s serious at the carlier age of many patients with rheumatic heart di ci e than at the older age at which atherosclerotic heart disease develop Protective Level in Chronic Cardiovascular Disease In chronic cardiovascular di ea e since any reduction of prothromlıın activity tends to inhibit thrombosis to ome extent even a moderate reduction gives adequate protection to many person Vright Marple and Bech have e tablished this principle in the treatment of myo ·127 CONTINUOUS ANTITHROMBOTIC DRUG THERAPY 200 mg Another 200 mg 1 gisen the second day, and 100 mg daily thereafter until the prothrombin content has dropped to 30 pxr cent The dosage necesary to maintain prothrombin actisily at 15 to 30 per cent is then determined After four weeks the daily dose is reduced by 125 mg (one half tablet) to permit an increase in prothrombin activity to 50 per cent U ually by the econd week the individual reaction to the drug is knokp and prothrombin act»ity need be measured only every other day by the third week twice kcells by the fourth week weekly and thereafter at increasing intervals to a maxinum of one month The monthly interval between tests is ſea ihle of course because of the greater safety from bleeding a ured bs main taining prothrombin at the relatively afe level of 40 to 50 per cent TESTS OF PROTHROMBIN ACTIVITY The value of any test of prothrombin activity is to reflect the relation to thrombosis and hemorrhage in the opinion of the majority of hema tology is and clinicians at the International Conference at Ba din 1951 there is no les uperior to the one stage Quick test for this purpose It now has the further advantage of widespread use and a wide pread correlation of at values with clinical results Brambel and Wise 34 observe Since this method measures changes in clotting rate as affected by ronprothrombin entities (activators) and hence give an over all picture of the clotting potentialities of blood it is a v elu) and practical tool for this pecific purpose The anticoagulant effect is a complex one which even today is not completely understood There may be prac tical advantages in certain instance however in the method of Owren which measures prothrombin and proconsertin and its modi fication by Ware and Strayde)The e methods gise accurate results as late as four days after blond is drawn whereas the Quirk te t mut b done within a few hours Owren suggested range of 10 to 30 per cant corre ponds to 39 to si per cent in the Quick cale (FIG 22) CHOICE OF ANTITHROMBOTIC DRUG The choice of a prothrombopenic drug reminds one of a choice aming the digitalis glycosides which likewise have a qualitatyvely simt lar action and of whick the mot effective the chcian finds are those *ith which he is most familiar Simularly the coumarin and phenyl indianedione dernaties are qualitatively alike in the effect on the ·126 SYSTEMIC ARTERIAL EMBOLISM an advantage over expectant treatment and is therefore the adual procedure, but such embolism in rheumatic heart disea e account fc only about fire per cent of clinical occlusion Emboli m to the aliace femoral arteries occurs in about 13 per cent and for these sites al surgery usually is indicated Against these le cr chances Jooms 1! 50 per cent incidence of cerebral embolism, with the graver sequel of death and disability, and with no hope as yet of effective operatio Whatever improvement may be promised by developments in curgie technic, embolectomy will remain essentially a palliative rather than preventive operation The tragedy lies in the probability that erjo occlusion often could have been presented if carlier minor emboli had been recognized and this applies with special force to cerebr embolism The important treatment in an acute epr ode therefore directed not at the fait accompl—the emboli m--but at presenti further formation and mobilization of the causative thrombi TREATMENT FOR SURVIVORS OF EMBOLISM After recovery of the patient from embolism protlırombını activ may be allowed to increase to between 40 and 50 per cent and aft a period of stabilization prothrombin activity need not be determine more often than once a month for most rheumatic patients For son patients cien a longer period centually is considered safe a tip other investigators Coogan Dans and Petersen find an interval six weeks satisfactory with some stable patients and Burt 10 spea of one to two months In patients with arteriosclerotic heart di ceke whom the dangers of hemorrhage are greater 1 period longer tha three reeks is inadvisable For four weeks following clinical emboli in the protlırombin Jerel maintained at 15 to 30 per cent because of the higher thrombot tendency in the acute condition This is the period of greatest peril recurrence in theumatic heart disease and iſ adequate antithromboe protection is withdrawn for even a day the chance of further emboli is high (FIC 5) Jf heparın is being administered during the acu stage, Dicumarol can be addedmanticipating its maximum effect about 48 hours The daily prothrombin time should be determined a blood sample obtained jut prior to the administration of heparı If the prothrombin content is 100 per cent of normal at the out 300 mg of Dicumarol is given on the first day of less than 100 per cena ·129 CONTINUOUS ANTITHROMBOTIC DRUG THERAPY prorty The criteria for selection of palients base been discussed previou l (21 That is the individual danger of bleeding? Are foci of bleeding pre ent or uspected? Although mo t bleeding in Dicumarol therapy comes from previou ly latent le-ions an increa ed danger maj le su pected from the patients hi tory If there are a ociated hyper tension and artenoscleroi the nk of cerebral hemorrhage u ually contraindicates the use of Dicumarol Anown gastrointestinal le on or previous bleeding may warn of ma ne hemorrhage (one of the mot serious but not fatal hemorrhages in my piperience occurred 12 a patient with an old apparently quiescent diverticulitis) In myo cardial infarction according to Bay 17 et al Dicumarol therapy 14 perm ible at there has been a hi tory of duodenal ulcer but no recent putabls hed bleedin, This policy particularly applies only ta short term therapy for prolonged treatment a more careful evaluation ? necesary Since liver di case in it-elf reduces prothrombın activity it requires pecial caution in treatment but it is not an absolute contraindication Renal impairment is undesirable and any renal lesion must Lic ena rately evaluated as a potential focus for bleeding but at lould a) o be remembered chat renal impairment may be due to repeated renal embolic infarction Although impairment of renal function may not be a con traindication for hort term therapy it increases the nl in long term treatment Fven though the patients physical condition will permit Dicumarol therapy his per anaht) or the cycumstances of his life may forbid the undertaking of a long range program that demands his close coop eration He mut be carefully educated in his responsibilties and obra ouk ke must be re ponsule to such education Only after everal die quirting esrls experterres due to our failure in this re Dect did my colleagues and I esohe a program which we con der ute Probably imilar di turbing experiences lase de couraged other physicians from further use of the drug patient printed as well as oral in tructions regarding the early inanifestations of abnormal bleeding but ome have not bech intelligent enough to follow these in tructions For example one of our paris patient who e Intelligence was ovete timated failed to observe tares feces recurring for several day Another patient moved away failed to appear ior te ts could not be located was kept supplied with Dicumatl by an unknown druggist deseloped 7049 hernaturia alter sit months and then came to the office The prothrombın actruly was ·128 SYSTEMIC ARTERIAL EMBOLISM prothrombin activity the chief difference being in speed and duration of action The phenylındanedione derivatives laic the disadvantage however, of sometimes causing agranulocytosi urticaria, and dermatiti Barher reports after having used Tromexan, phenylındanedtone and cyclocumarol, we came back agun to Dicumarol” Foley suggests, 100% 90% 807 70% 60% OWREN WARE AUTHOR 50% BRAMBEL FORD HOSP PROPHYLACTIC RANGE NICHOL AND WRIGHT QUICK SCALE 40%- 584-44* MAYO CLINIC BRUZELIUS 305-401 ,572 397 39% 457 30-40t 30% EXPRESSED IN TERMS OF QUICK TEST 20% 42% 18% 10% 30% 10% 314-12% 0 Fic 22 Comparıson of degrees of anticoagulation therapeutic range of various authors (By permi sion from Smith T J and Schelling V The clinical comparison of laboratory methods used in controlling oral anti coagulant therapy in Thrombosis and Embolism I'roc I International Conference Basel Benno Schwale & C 1951) as quite a series of Dicumarol (dicoumarin) deris ative are available and all have been used successfully the choice will be determined primarily by the price In this al o the choice resembles that of a digitalis preparation My associates and I have had similar experience to Barker s–Tromexan and phenylındanedione live been found prel erable in a few instances but after trying these and other agent 1c have revcrted to Ducumarol using it in prolonged therapy for more than 300 patients with thromboembolic conditions SELECTION AND EDUCATION OF PATIENT Before a patient can be considered eligible for continuous treatment several questions must be answered (1) Is the patient with mural stenosis eligible for taloplasty? If so this treatment should lasc ·131 CONTINUOUS ANTITHROMBOTIC DRUG THERAPY a time to tell me then explained to him who I did not tell lum While I am not entirely clear in my memory I think he tated he would huse hesitated to remove the tooth if he had known I was taking ap anticoagulant Within half an hour after the extraction I think all blerding had stopped and a clot had formed Ten other patients have had dental extractions while taking Dicumarol without difficulty írom bleeding Another patient ga hed his leg while fishing in Northern California and consulted a local doctor The leg was bleeding onk moderately and required only a pres ure bandage When asked later if he hail told the doctor he was taking Dicumarol he aid No I thought it mught inghten hum These instances although eloquent of the degree to whsh fear of bleeding can be conquered emphasize on the other hand another danger--that of overconfidence on the part of the patient, and a failure on our part in proper education Another warning to the patient, therefore must not be oserlooked Neier omit reporting the use of Dicumarol to a physician or dentist and always consult the personal physician in addition the po sıkılıty of an accident with loss of consciousness must be considered A physician patient carries a card which says I am taking Dicumarol as a medicine in ca e oi injury of even minor degree get medical attention Immediately control bleeding by firm pres ure at the site of hleeding We are nou giving imular card to our other patients Unu ual cycum tances at tymey may lead to the u e of Dicumaro! when a trong possibility of severe bleeding may be prelerable to the trong po ibility of serious clotting Bay et al 17 mention a patient who even preferred the nk of another massive gastrointestinal hemor thage from a peptic ulcer (he had had three) to the rk of another myocardial infarction (he had had thot and insisted on being given Dirumarol Mo i patients shok little concern about occasional bleeding such as puspur hlotches occasjonal coning of the gums when the teeth are bru hed or epi tasis as long as they understand. The con cern of a phy clan about unpredictable bleeding which a frightened patient of family mi interpret as caused by faulty treatment may largely be averted if the possibility of bleeding is properly explained Serious bleeding in a carefully selected patient with the prothrombin lesel k pt at 50 per cent of regalar relable prothrombin determinations are made is rare ·130 SYSTEMIC ARTERIAL EMBOLISM lens than 10 per cent The bleeding stopped following the adminitration of utamın hı, and the prothrombin concentration quickly rose to normal Since then no patient is accepted for continuous treatment without inore critical evaluation In addition to his intelligence and cooperation the patient mu t have an understanding of the objective of treatment mu t realize the neces sity of continuous treatment, and must accept the calculated rid of blecdıng If the physician has to bear the complete reponsibility for treatment this form of therapy is inadusable Both the benefits and the dangers are explained frankly and the treatment can then be restricted to those willing to undertake their share in a continuing responsibility Patients are instructed and educated reguding their con dition much as a diabetic patient is regarding diabetes The under tand ing of objectie versus dangers by such carefully screened patients is often quite gratifying They become intere ted in their prothrombin les els and Dıcumarol dosage and accept minor bleeding without alarm The opposite danger to undue fear however occasionally arises the danger of the patients overconfidence One patient an attorney who needed a dental extraction badls was loath lo discontinue the Documarol because he had two mild cerebral thromboses when he stopped it previ ou ly His statement I would rather bleed than clot Doctor i allu trative of his degree of understanding His oral surgeon was al o ju t: fiably loath to extract the tooth unles Dicumarol was discontinued Because of previous experiences with dental extraction without diffi culty, we convinced him it was safe lhe attorney wrote him a letter accepting the rik The dental extraction was accomplı hed without abnormal bleeding The following year it was nece-sary to extract another tooth I consented assuming the same oral surgeon would be used He had retired however and the attorney nos firmly convinced that the fear of the physician often tran-cends that of the patient wrote me when the time came to have my upper right molar removed and I found that Dr -- had retired from practice I did not tell the extractor for fear that I would have the same trouble with him that I had had with Dr A few minutes after the extraction I a led him if he was going to pack it lle said no that he did not beliese in packing a tooth cochet-a natural clot was be! I then told him that there might be difficulty in a natural clot formation as I was then taking Dicumarol and my prothrombın lesel 1 74 between 25 and 30 per cent I remember very di tinctly that he replied This is a hell of ·CONTINUOUS ANTITHROMBOTIC DRUG THERAPY DISCONTINUANCE OF DICUMAROL The chief weakness in continuous antithrombotic drug therapy las heen the danger of interrupting it for any rea on including operation Such withdrawal of the drug not only re tores the original r1 L of emboli m but according to the experience of many phy icians temporarily increases the nk Of 17 patients observed by Coemetall embolism recurred in 12 after Dicumarol was withdrawn--in eight of thee within a month Wright it reported erious thromboembolim in 10 of 12 patients with Theumalic heart di ease who were not con tinuou ly treated and five of the e died after withdrawal of the drug Discontinuance prior to both minor and major urgers has been con sidered mandatory although in certain instances serious emboli m has occurred One patsent reported by Wright ?! had two ay temic arterial embolt when Dicumarol was discontinued before a dental extraction Facquet Hu on and Ducrot tº reported a death from cerebral embo 11 m ocurring whers Dirumarol was di-continued prior to dental extrac tion My own experienre with a number of patients undergoing dental extraction indicates that it is unneces zry in most in tances to top the drug' Olwin 595 ciles an in tance of fatal cerebral embol mix days following withdrawal of Dicumarol in preparation for mitral valio platy The danger of formation and evacuation of a fresh clot is admistedly greatest al miral vah oplasty where the outce of the emoh 19 the very site of operation and where the operative procedure it els may di fodge a clot A large eries tudied in this connection is that of Ell and Elarken The problem is usually presented they find when a patient has already had one or more penipheral emboll In their fir 1 500 patients 79 had had emboli and mo ! of thest " were In aufsrular fibrillation O[ the e 17 (more than one out of five) suffered operative embolism in the next 300 patient, however although th proportion of patients with previous embol m was greater (there were 601 onlix of them (1 out of 101 had operative emboli m The nk was far greater in patients in Group 4 (20 per cent} than in Group 3 17 per cent) Mot important supre about half of all urgically induced embohi are fatal the possibility of embolism adds at leat three per cent to the danger of death at operation Thus the po ibility of operatuse emboli i ha been ignificantly decreased as our experience has increased these authors contment but it to ·132 SYSTEMIC ARTERIAL EMBOLISM Laboratory Control One other consideration may be described with a brevity that perhaps does less than justice to its importance laboratory control and the supervision of the patient < regimen In my practice, one secretary keep records on all patients recen ing Dicumarol supervises appointment for regular laboratory tests, and telephones every patient who fail to heep an appointment If the patient seems unlikely to mamlan lus cooperation the drug is gradually discontinued Laboratory accuracy 18 guaranteed by the work of two reliable technicians who hve made the tests for many year The printed instructions given each patient may seem to be unduly alarming at first reading Properly explained they are not Tlicy merely alert the patient to complications Printed Instructions Given Dicumarol Patients erious if Because of heart disease or chronic thrombophlelıtıyou are receiving a drug which normally tends to present clot forma tion (Dicumarol or Tromexan) While the e drugs should be helpful in the treatment of your di esse there is a pro sbility that they may cau e hemorrhage which can be very not checked Hemorrhage ordinarily can be cheched and con trolled if it is promptly reported to your doctor Symptoms to be reported are Bleeding from any area Nosebleed oozing gums or ruptured skin ve el Coughing of blood Vomiting of blood Blood in the urine (red black or coffee colored urine) Bloods black or tarry tool While taking the e drugs you should not take alicylates (aspirin Alka Seltzer Empırın etc ) or liquid or medicinal aron It is al o adusable while taking these drur not to take any patent or adverti ed medicine without consulting your physician ce 110 an occ3 We employ the e precautions about salicy lates wlule detcrinınıng the maintenance dose of Dicumaro! Wher thus is e tabl, hed » reason to deprive a patient of a small dose of alıcılates a sional analgesic The dose needed to induce a significant prothrombın reduction is quite large (over sit grams a day) ·135 CONTINUOUS ANTITHROMBOTIC DRUG THERAPY cannot present all sentriculas clats in myocardial infarction it is wishful thinking to assume it can present all left auricular clots in rlieumatic heart diese Ren en 109 ajs We have a u picion that active antı coagulant therapy belore operation makes the thrombus in the left atrium more friable llorn concurs 118 We heartıly agree with Ren en that in all probability antiroagulants keep the thrombotic material in a more friable gelatinous fait and increa the danger of embolus when urgical manipulation is to be undertaken Janton ? 5 report Quite a few of our patients have been on Ducumarol over a period of one two or more years in every one there was a clot and the center of the clot was soft and of currant jelly consi tency Wright 13 however belles per the opposite that mural thrombi in the hearts of patients treated for ten dave or more with anticoagulants tend to be more atmoothly sealed over with a fibrin coating and to possess fewer friable and regular fibrillating tas? Suscp Dicumarol 1s usually discontinued before operalion sa po able that the gelatinous friable clots deacribed by Ron en llorn and Janton were tho e that formed during the preoperatne period when the drug was di continued As a ze ult of these varying opinions how ever the advisability of the preoperative use of Dicurarol 19 not agreed upon Ren sen sa18 199 We use no anticoagulants for a larger [ac] period preoperatively Horn 118 lates We do not u e anticoagulants esther before during or after urgery and do not believe they are indicated Wright ? It appears logical to place patients on anti coagulants for from ten to thirty days in preparation for a commis surotomy despite the prevent lack of tati lical proal of its value The final proof of the effectivene s and afety of Dicurarol gren throughout the entire preoperative period mu I come from the surgeons RESULTS FROM DICUMAROL BEFORE AND DURING OPERATION An important experience in this field in that of Storm and Hansen 1 With Vullertz 234 these in eligat its maintained entithrombotic prophy laxı through 54 thoracotomies for lung cancer and other di eases in patient for whom the risk of interrupting prophylaxis seemed too great The loss of blood during operation was determined they report and found to be normal as compared with a group of untreated ·134 SYSTEMIC ARTERIAL EMBOLISM remains a little higher in patients who have had previous embol than in the series as a whole " Belcher and Somerville O report a comparable experience Tive of their 54 patients with preoperative embol (9 per cent) had further embolism during valioplasty or shortly afterward A typical case in my experience was Case 9 in CHAPTER 8 Dicumarol was discontinued two weeks before operation The pathologist reported that "the inner surface of the appendage is almost completely covered by white, organized thrombus while the small lumen remaining con tains fresh purple thrombun” Four days after the operation cerebral embolism occurred The approximate risk of embolisin at operation in patient with previous embolism, therefore is about 10 per cent (5 per cent in Group 3 20 per cent in Group 4), and death results in probably half of such accidents If this hurdle of operation is surmounted" Ellis and Harken sa conclude the likelihood of late embolization is not great ' By the very operation-the mitral valve opened the auricular appendage removed—the thrombotic milieu is destroyed, through elimi nation of stası Any subsequent embolism therefore is unlikely except from clots already pre ent at operation Inasmuch as operative emboli are invariably red and recently formed it is probable the clots have formed in the short preoperative period during which coagulability has been allowed to return to normal The old organized fibrous clots are not u ually dislodged Most recently formed clot of undisturbed presumably have a 50 per cent chance of becoming attached and not ejected (TABLE 5) but the clots formed just prior to operation may not have even this chance Within a few days an exploring finger de pite all precautions may be the factor that precipitates embolism If the patient should be protected against the formation of fresh preoperative thrombı this requires the use of Dicumarol started at an adequate time before and continued throughout operation To justify such treatment the drug must be shown to be effective and the danger of hemorrhage less than the danger of operative embo lism First it must be established that the use of Dicumarol can effec tively reduce the incidence of left auricular thrombi and can also affect the clots already present beneficially and not harmfully There is no apparent disagreement regarding the effect of Dicumarol in oppoing the formation of clots but there is a sharp division of opinion regarding the effect on the character of a clot which may form despite Dicumarol or of an old clot which already has formed Since Documarol ·115 CONTINUOUS ANTITHROMBOTIC DRUG THERAPY cannot present all ventricular clats in myocardial infarction at 18 m hful thinking to ar urme it can prevent all left auticular clots in theumatic heart dease Ren sen ** 23º Be have a suspicions that aclise antı coaoulint therapy before operation makes the thrombus in the left atrium more friable Horn concurs 118 We hearinly agter with Ren en that in all probability anticoagulants keep the thrombotic material in a more friable gelatinous state and increa e the danger of embolus when urgical manipulation to be undertaken Janton report Quite a few of our patients have en on Ducumarol over a period of one two or more year in every one there was a clot and the center of the clot na olt and of currant jelly con 1 tency Wright" however believes the opposite that mural thromb in the hearts of patients treated for ten dav> or more with antiroagulants tend to be more smoothly sealed over with fibrin coating and to possess fewer friable and irregular fibrillating au → Sin e Ocumarol is usually discontinued before operation it* po able that the gelatinou“ friable clots described by hen en Jorn Ann Santon were tho e that formed during the preoperative persods hier the drug was di continued As a result of these varying opinions how per the advi ability of the preoperative use of Dicumarol 19 not agreed upor Pen en says 19 Weu e no anticoagulants for a large { c) period preoperatives Horn 118 tales We do not u e anticoagulants either before during or after surgery and do not believe they are indicated night 13 It appears logical to piace patients on anti coagulants for from len to thirty days in preparation for a commis Surotomy de pite the pre ent lack of satı tical proof of ils value Th fral proof of the effectivenes and afety of Documarol geven throughout the entire preoperatie period mu t come from the urgeon RESULTS FROM DICUMAROL BEFORE AND DURING OPERATION An important esperience in this field » that of Storm and Han en 17 Tith Mulleruz these investigators maintained antithronibotic prophy laus through 54 tkoricotomjes lung can er and other di ea es in patient for whom the nk of interrupting prophylaxis seemed top Teat The loss of blood during operation was determined they report and found to be normal as compared with a group of untreated ·136 SYSTEMIC ARTERIAL EMBOLISM patients They later maintained Dicumarol therapy through mitral valoplasty in 26 cases, finding hemorrhages no greater than in 26 control operations studied at the same time, or un 50 similar operatione performed in previous years of the 26 patients protected by Documarol none had thromboembolic coinplications in the three or four weeks following operation although sesen had had thromboemboli m How cier a fresh auricular thrombus was found at operation in one patient who had recensed Dirumarol for only ix days before operation Either the clot had formed before the drug was started or Documarol nas ancſfeche In the 26 control patient four had operative cerebral embolism which was fatal in one case and caused residual paraly is in another a fifth patient had a probable cerebral embolı m Antithrombotic Preparation for Operation Several preoperative procedures using antithrombotic drugs have been advocated in an attempt to present operatre embolism 1 Dicumarol may be adminiatered before valvopla ty to all patients but discontinued before operation This is ba ed on the belief that Dicumarol not only inhibits formation of new clots but al o rendera previously formed clots le s friable and lc s likely to be ejected Thi is inferred from the evidence of Burchell 38 that mural clots formed durin, D.cumarol therapy in myocardial infarction are le « readily ejected from the work of H P Wright » O showing that venous and arterul clots in rabbits are more rapidly canalized with Drcumarol therapy than in its absence and from the observations of I Wright As alrendy discussed others disagree that clots are rendered le « friable This procedure may prevent the early formation of clots but does not protect against them the lat few days before operation of the drug is discontinued 2 Dicumarol may be usthdrawn before operation in tho e who are receiving the drug for embolism but the antithrombotic effect may be maintained up to the time of operation by substituting heparin intra 1enou ly for Dicumarol This is the decontrol method adıocated by Olvan 180IIcparin and a coumarın or phenylındanedione derisative are gucn after operation This controls a patient to the moment of opera tion and respects the surgeon s fear of inerea ed hemorrhage during the operation with a lowered prothrombin activity Likoff 13 also believes in continuing Dicumarol until immediately before operation, perhaps ·CONTINUOUS ANTITHROMBOTIC DRUG THERAPY 51 ht up to the point of operation the patients blood coagulability can be controlled with quick acting drugs uch as hepatın 3 Bucumarol may be given to every patient as a preoperatie meas ure and continued through the operation and for several weeks after as advocated by Storm et al 3 I Vore selectively Dicumarol may be given before during and after cardiotomy only to those patients in whom the ni of operative embro 11 m 13 con dered high-those patients who have had previou ly diamo no ed embolic episodes since suppo edly they face a nih of a 20 per cent incidence of emboli m (if in Group 4) and a 5 per cent inci dence (of in Group 31 Whether all patients who undergo valvopla iv hould recere Da vinarol as uggested by Storm et al mu t be deler mined by further experience in patients with previous emhol m how ever the high incidence of operate embohom soulil sem to you by the contmuance of the drug before during and for a host time after opera con l' ankthrombor drugs have been applied long enough Before operation few tre h and potentially embolic clots hould be present The final possibility that clots might desclop at the uluse linc after operation can be eliminated by maintaining antithrombotic drug therapy for a week or two until this danger is pa t Although the prothrombin activity is often abruptly elevated by the use of blood tran lu sons during operation the operation itself removes the most important factor in thrombosis-stası What of the Converse danger--that hemorrhage might occur pot operatively ma surgical wound' In the experience of Storm Hansen and Vullertz 37 38 this does not occur it might be argued in fact, that ans potential ite of hemorrhage would be readily evident at opera tion and could be repaired immediately Bleeding into the pericardial cavity when the drug is first tacted followige operation has occurred to begin Dicumarol soon after operation is probably not advı able since a surgical incision that might not bleed at a 100 per cent level of prothrombin during the operation moght and of cour e did ton those in tances of postoperatie bleeding) when the prothtomb activity as lonered after operation SUMMARY 1 Continuous antithrombotic drug (Dicumaro!) trtatment is indi ated for patients with mitral tenosis and stetric arterial embolim who are ineligible for mitral als oplasty and eligible for the drug ·138 SYSTEMIC ARTERIAL EMBOLISM 2 Continuous treatment also is indicated (if facilities are adequate) for patients who survive a severe or recurrent myocardial infarction or even for those who develop the anginal syndrome not responding to other treatment 3 Continuous Dieumarol treatment is safe for the ambulatory patient of the physician is competent, the patient carefully selected, and the laboratory reliable 4. 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LIEBERSIAN J Symons, C, AND IILEBVER R Long lerm anti cogrulant therapy Circulation 9 748 1957 275 AND FOLEY VT Use of anticoagulant in trealment of heart dira Am J Med 3 718 1917 26 MARPLE, C DAY» Deck DF Myocardial Infarchion Is Clinical Vanestations and Treatment with Anticoagulants New York Crane & walton, 19 p 219 LRDANETA E AND WRICHT B Re-opening the care of the abdominal aortic a titysm Circulation 13 751 1936 248 WOOD J CA Cory HL, JR Prevention of systemic arterial embolim in chron rheumatic he di ea e by means of protracted anticoagulant the rape (rculat: 10 514 1933 2) Wood P An apprec alson of mitral tends Bat) 1 48 0 1951 280 SHRADER EL DAWEL, VB AND ORACLES Y Coror ary citibol in Carculat n11259 1956 81 BACGER VI BJORKO AND VALMISTI ON ( Technique and sequelae of cath lerization of the left s de of the heart Am Heant 53 91 1927 ·152 SYSTEMIC ARTERIAL EMBOLISM 218 TOWBIN A Recurrent cerebral emboli m Arch Neurol & Pychiat *3 173 1955 219 TR 4CERVIAN LJ AND CORLEY CL Rheumatic le ions in left atrial ar pendages Calfornia Med 82 163 1935 250 TROPEA F AND EVTIVE J Peripheral emholization following mitral com mi urotomy Arch Surg 67 43 1953 251 TULLOCH I AND WRIGHT IS Long term anticoagulant therapy Circula tion 9 823 19.1 252 VIEUSSENS R Traite nouveau de la tructure et des cau es du movement naturel du coeur (Toulouse 1715) in Vajor RH Cla ic De criptions of Di ea e ed i Springfield Charles C Thoma 1932 p336 203 VIRCHOW R Gesammelte Abhandlungen zur wi en chaftlichen Medicin Frankfurt Sohn and Co 1850 chap 1 r 221 251 lov GLAUV VC The pathology of rheumati m Am Ved 2 76 1917 255 WALLACIS J B LUKASIE L AND ANGRI T A A Source of embol in theu matic heart disea e Am J Clin Path 21 172 1951 256 LUKASIT L AND ANGRIST A A Mechanı m of death in theumatic heart dı ea e in different age periods Am J Clin Path 26 360 1936 257 WARD S B Emboli m of the arteries of the extremities New York V J 19 257 1874 258 WARE A G AND STR AGNELL R An improved one stage prothrombin method Am J Clin Path 22 791 1952 259 WARE ER Ca e Report Presented before the Pacific Interban Clinical Club 1918 260 WARREN RAND LINTON RR The treatment of arterial emboli m New England J Med 233 421 1918 261 AND SCANNELL J G Arterial embolism Recent progre Ann Surg 140 311 1951 262 WEDGWOOD JEarly diagno is of subacute bacterial endocardit Lancet 2 1058 1955 263 WEISS S AND DAVIS D Rheumatic heart disea e III Embolic manife is tion Am Heart J 945 1933 264 WESSLER S COHEY S AND FLEISCIINER F G The temporary thrombotic tate New England J Med 251 113 1936 265 WHITE PD AND BLAND E F Vitral tenosis after 80 JINA 116 2001 1911 266 WILKINSOY AB Ob ervations on aortic embol m California Wed 76 311 1952 267 WILKINSON WR Arterial embolectomy Report of succe fui aortic femoral and popliteal embolectomie Am J Sur» 85 648 1933 268 t»EART JH 4 CH49314 C B Dicumarol therapy in conge ine heart failure New England J Ved 239 701 1918 269 WRICIIT HP KUBIK M M AND HAYDEN V Influence of anticoagulant administration on the rate of recanalization of experimentally thrombose ] vein Brit J Surg 10 163 1932 ·155 INDEX Endothelial damage D.cumarol Therapy-Contd in thoracotomy 1 16 of arteries 17 of left sarcie in myocardial infarction 11! 11 theumatic heart disa 53 51 toabinuous therapy 11119 dangers 115 in Donbacterial frombotic en locar glural thrombi prevention of 113 ditis, 11 in rheumatic b an di ea of lett venircle continuous after embols m 126 ca arteria cleronic hean de rise 45 in endocardial fibroela toy 9 ver us operation 110 bleedinin 124 [leart di ca e for recurrent embo) m 10 prothrorabın le el deaitable in 122 as eu e of embolt m See Embolim arterial sy tomc Dig talis 65 68 69 70 71 art rio cleric See Anetyo chetoric bear d sent Esbolism art pal, sy temic th umatic See Rheumatic heart 1 calcific See Embol source cau-es of 9 Ilean failure Se also & circulatory er bral, 12 congestisc Uncal orrelation of 33 documstolun ))7 18 death and di ability it in mitral steno is Mortality rate in 21 22 23 26 42 auricular fibrillation in 39 40 41 101 lelt Auncular failure on 31 diagnost Hemortha e Sec Ilceding clinical recognition 15 93 HI, torical review 1 dflorentiation from thromto 14 16 di inkurran, 9 32 11 Infarction embolettomy for 21 21 myocardial See Myocardial inlarction senal 12, 15 me enttie i5 61 pletuc. 15 10 myocardial infarct op S Myo ar Petracardiac clotting See Thrombo 19 dal inta ction cardiac mural Paradoxt 10 intrava cular clotting See Thrombosis peripheral 9 vascolar previous attacks in 30 pulve in 92 94 Left auricular thrombosis See Throm currence 26 30 133 bo cardiac musa) ta that heart d seases Rhey Lell aurice that hart disease catheterization of 41 42 97 plene 12 dangers 41 47 97 tv al trom 27 105 110 Se a) so d latalion of 75 1677 1887 Embu math and dssability oute 9 10 16 17 18 1105mal 56 Fndo as fil yo la 10-> in matsal stel s19 9 in aormal rhythm 515 Endoc dla in ayrical fibrillation 56 Aontacte al ah narit 17 Left senteticufer thrombols See Throm ubacute bacterial, 9 97 bos cardiac mura) olume ·Inder ar Angiocardiography 91-97 survival of patients 31 Aneurysm in rheumatic heart di ea e aortic as ource of emboli 10 age of patients in 56 cardiac 45 61 111 Lleeding Annulus fibro u calcification of 89 cerebral 124 Antithrombotic measures See also Dicu lesions causing 123 marol therapy minor 123 in arterio clerotic heart di ea e 111- prothrombin level safe 122 in rheumatic heart di ea e rarity in 117 121 in theumatic heart di ease 99-101 Aortic plaque as ource of embolus 48 in therapeutic range 121 123 vitamin I preparations for 121 Aortic steno 1 left ventricular throm Blood bosis in 41 coagulability 49 Arteries laboratory tests for 49-51 embolism to See Emboli m arterial hypercoagulability 51 occlusion of 15 16 serum prothrombin conser son ac Arterial embolism See Emboli m celerating factor in 49 terial systemic platelets 49 Arterial occlu ion 15 16 17 See also Blue phlebitis (phlegmasia cerulea do Emboli m arterial systemic lens) 48 122 Arteriosclerosis 48 Buerger s di ea e 48 122 Arterio clerotic heart di ease See also Cardiac aneury m See Aneury m Embol m Thrombosis diac diagnosis of differential 82 87 89 Cardiac mural brombus See Throm Arteritis 48 122 bos cardiac mural Auricular fibrillation Cerebral emboli m See Emboli m brain in arteriosclerotic heart do ease Clots See Thrombo is left ventricular thrombosi in 45 Coagulability See Blood coagulability 46 Congestive heart failure See Heart fail mobilization of thrombı 61 68 ure conge tive Aschoff bodies in 53 auricular endothelial damage in 53 Dental extraction 133 auricular tasis in 55 56 Dicumarol therapy See also intithrom left auricular dilatation in 55 56 botic measure in middle age 82 action of 101 in mitral regurgitation 53 on old clot 31 in mitral stenosi bleeding in See Bleeding duration of de ea e index of 56 in conge tive heart failure 9 117 at dental extraction 133 left auricular thrombo is in 36 at operation murmurs disappearance of 8) in mitral talvoplasty 135 right heart failure in 33 154 ·INDEX 157 Thrombo 1-Contd platelet 4 48 a cular 9 10 12, 4, 48 49 9 Thrombo is, mural leit Burcle 19 rheumatic heart diseac auncular fibrillation in 37 clinical correlations of 33 diagno is, angiocardio-raphy 91 dia 10 is emboli ma index ol 83 con esse heart failure in 31 33 36 in mutral regurgitation, 53 in mitral sleng is 33 36 in mitral steno is with mitral re gurgitation, 53 lesions underlying thromt. A choff by lies in 53 51 in theumatic rarditis, & ule 51 mobilization a mot 61 60 in nonbacterial thrombotit endocar diti 17 left ventricle clinical correlations, 411 pathologic correlation with infarct in endocardial fibroela to 9 mobilization as emboli 68-71 right aunele D 12 night ventricle 7 Lussbow Bydolph 1 ·156 SYSTEMIC ARTERIAL EMBOLISM Lupus erythemato us systemi. 48 thrombosis in 48 Vitral regurgitation diagno i 36 42 lelt auricular thrombosis in 53 Vitral stenosis auricular fibrillation in See also Au ricular fibrillation with right heart failure 33 diagnosis accuracy of 36 42 embolism Sec Emlolism arterial sys temic left auricle size of See Rheuniatic heart di ea e left auricle left auricular thrombo is in Sce Thrombo cardiac mural Vyocardial infarction See also Thron cardiac mural cmbolism in 12 See also Embolim arterial lemic urvivors Dicumarol treatment of 119 survival with 120 death type of 120 thrombo is in See 1 hrombo 15 car diac mural Pulses See under Emboli m arterial systemic Recurrent embol m See Emboli mre Current Rheumatıe arteritis See Arteritis rheu matic Rheumatic fever diagnost 81 I heumatic heart di ea e auricular fibrillation See Auricular fibrillation diagno is chnical 18 differential 73 80 83 emboli m di clo ing diagno1 83 In mitral steno 83 85 86 88 89 pre umptive 91 einboli min 37 39 10 prophylactic mea ure 99 101 left auricle in 56 87 pathologic stage 77,8 prophylaxi 99 bo! de Senac Jean Bapti te 4 Serum prothromhan conser son acceler alor (SPCA) 49 51 Streptococcal infections prophylaxis in 99 Stasi circulatory in arterie 118 in heart in left duricie 55 degree and duration of Sy in auricular fibrillation 56 in left ventricle 58 Prothrombin activity after arterial embolism 126 tests of choice of 127 laboratory control 132 Quick test one tage 127 reduction by salteylate 132 Owren te 1 (prothromin and pro convertin) 127 Ware and Stragnells test 127 therapeutic range 122-124 Phlegmasia cerulea dolen 48 122 See also Blue phlebitis Polyarteritis thrombosis in 48 Prognosis in embolt m See Emboli m artena! sy temic in thrombosis See Thrombo 19 Terminology 2 3 Thromboembolism Ser Embolt m Thrombo s Thrombo is arterial See va cular all 61 67 72 cardiac coronary 22 predation of thromi 044 51 predi po ition of certain area 51 ·INDEX 157 Thromato - Coord plalelet, 48 4-cular 9 10 12 17 19 49 99 Thrombosi mural left auncie In rheumatic heart di ta e auricular fibrillation in 34 clinical correlations of 33 diagno is angiocardiorraphy 91 danno embols m as indes of 83 conge he heart failure in 31 30 36 in mural regur itation 53 in matral stenosi 33 36 in miiral steno ) with mitral re gurgitation 53 lexions underlying throml, A choll bodie in 53 51 en Theumatic cardit) arute 51 mot tlıcation & emllı 61 fax in nonbacterul thrombotie en locar otrs, 10 left ventricle cl nical correlati n 41 42 pathologic correlations with infarct in endocardial fil rocla 10 : 9 molilization & embol 68 71 night auricle 10 12 Ti ft Sentricle 7 Varcbow Rudolphs *