Clinical pathologic conference "Hole-in-one" sudden death: Mitral stenosis and left atrial ball thrombus J. T. Lie, M.D., F.A.C.C. M. L. Entman, M.D., F.A.C.C.* Houston, Texas
Case presentation An 83-year-old woman was brought to the hospital on Aug. 16, 1973, by her daughter, after having "passed out" three times on the day of admission. The daughter related t h a t each of the syncopal episodes was sudden in onset and lasted only a few seconds, and that the patient had no seizure activity, although she was incontinent of urine. The patient had been reasonably well all her life. She had a vague history of hypertension, treated intermittently with Reserpine. In addition, diabetes mellitus had been previously diagnosed and she had been taking oral hypoglycemic agents since the age of 75. She had complained of occasional episodes of exertional chest pain t h a t were relieved by nitroglycerin, and, several years previously, mild symptoms of congestive heart failure. Despite this, the patient did not consider herself to be limited in her physical activity on a routine daily basis. In 1970, the patient had an episode of transient aphasia, right hemiparesis, and right hemiparesthesia, but recovered completely from these within a short period of time. She was found to be in atrial fibrillation with a slow ventricular response and was started on a maintenance regime Qf digoxin, 0.125 mg. daily, in addition to oral hypoglycemic drugs and Reserpine. From the Departments of Pathology and Medicine {Cardiologyh Baylor College of Medicine and Ben Taub General Hospital. Texas Medical Center, Houston, Texas. Supported in part by United States Public Health Service Grant HL17269 from the National Heart and Lung Institute. Received for publication March 8, 1976. Reprint requests: J. T. Lie, M.D., Department of Pathology, Baylor College of Medicine, 1200 Moursund. Houston. Texas 77025. *Howard Hughes Medical Investigator.
798
Fig. 1. Chest roentgenogramtaken on Feb. 27. 1972. some 18 months before death, showing slight cardiomegalyand interstitial pulmonary edema.
She was next seen on Feb. 22. 1972, complaining of mild dyspnea on exertion and a cough. Physical examination revealed wheezing and rfiles in the lungs, but no elevation in jugular venous pressure. Cardiac examination was negative. Chest roentgenogram showed mild cardiomegaly and interstitial pulmonary edema (Fig. 1), and the electrocardiogram (ECG) showed slow atrial fibrillation as before. On routine follow-up a month later, the patient's chest roentgenogram was clear and she was asymptomatic. At that
June, 1976, Vol. 91, No. 6, pp. 798-804
C P C - M i t r a l stenosis a n d left atrial ball thrombus
Fig. 2. ECG taken on Aug. 16, 1973, the day of death, showing atrial fibrillation with a ventricular response of 80 per minute.
t i m e the cardiac e x a m i n a t i o n revealed a systolic ejection m u r m u r , but was otherwise u n r e m a r k able. T h e p a t i e n t c o n t i n u e d to do well and ret u r n e d for a routine hospital visit on Aug. 23, 1972. and was found again to be in atrial fibrillation with a h e a r t rate of 60 per minute. Cardiac e x a m i n a t i o n at t h a t t i m e described a G r a d e 2/4 diastolic r u m b l e h e a r d best with the p a t i e n t in the left lateral decubitus position. In addition, a third heart sound was h e a r d which was described as an opening snap. T h e p a t i e n t was referred to the cardiac clinic with the diagnosis of possible r h e u m a t i c h e a r t disease. Chest r o e n t g e n o g r a m a t this t i m e was again essentially negative. T h e p a t i e n t was seen 2 m o n t h s later in the cardiac clinic, where a physical e x a m i n a t i o n was completely n o r m a l a n d no m u r m u r s could be h e a r d by several cardiologists. In March, 1973, the p a t i e n t h a d a n o t h e r episode of d y s p n e a a n d she
American Heart Journal
was found to be in n o r m a l sinus r h y t h m with P R i n t e r v a l of 0.24. A chest r o e n t g e n o g r a m at t h a t t i m e showed some mild venous congestion, but no f r a n k p u l m o n a r y edema. T h e p a t i e n t r e t u r n e d a week later for a r o u t i n e visit and was a s y m p t o matic. In June, 1973, the p a t i e n t was seen in the h o s p i t a l and for the first time since August, 1972, the diastolic r u m b l e was heard along with an a u g m e n t e d first h e a r t sound. No opening snap or third h e a r t sound was h e a r d during this visit. T h e clinical impression a t the time was t h a t the p a t i e n t p r o b a b l y h a d mild r h e u m a t i c mitral stenosis, and because of her age, no f u r t h e r studies were indicated. T h e final episode b e g a n on Aug. 16, 1973, when sync0pal a t t a c k s occurring earlier t h a t d a y b r o u g h t the p a t i e n t to the hospital e m e r g e n c y room, where she experienced no f u r t h e r s y m p toms. On admission, her blood pressure was
799
Lie and Entman
140/100 mm. Hg and she h a d a pulse rate of 90 per minute. However, some time during the course of her time in the emergency room, a peripheral pulse of 32 per m i n u t e was noted. S e r u m electrolytes were n o r m a l and the ECG revealed atrial fibrillation with a ventricular response of 80 per m i n u t e (Fig. 2). T h e p a t i e n t claimed t h a t she felt perfectly well, and was instructed to stop taking digoxin for 2 days and to r e t u r n to the hospital for a follow-up evaluation. W h e n she was a b o u t to enter her car in the hospital parking lot, she experienced a n o t h e r sudden syncopal episode, and was taken back to the hospital as she was recovering. By the time she arrived in the emergency room, however, she was comatose and found to be in cardiorespiratory arrest with no peripheral pulses. An E C G showed narrow QRS complexes at 20 per minute, and cardiopulm o n a r y resuscitation was applied. T h i r t y minutes later, the ECG had become virtually a flat line. and she was cyanotic. S p o n t a n e o u s respirations were weak and i n t e r m i t t e n t , and the pupils were fixed in the mid position. J u g u l a r venous pulse was fully distended and the h e a r t rate varied from 100 to 150 beats per minute. She died shortly thereafter. Clinical discussion DR. M. L. ENTMAN: This is the story of a w o m a n who was found to have the late onset of a diastolic rumble, diagnosed as probably of rheumatic origin. It would be extremely u n u s u a l for a w o m a n to remain a s y m p t o m a t i c from mitral stenosis until her 80's and not have signs of left atrial enlargement, a past history of congestive h e a r t failure, or a past history of r h e u m a t i c h e a r t disease. It has been estimated t h a t the average time between the onset of r h e u m a t i c h e a r t disease and the onset of s y m p t o m a t i c mitral stenosis is 20 to 30 years 1 which would place this lady's episode of r h e u m a t i c fever (if t h e r e were such an episode) in her sixth decade. Although all things are possible, we must therefore consider the possibility t h a t the diastolic m u r m u r in this case e m a n a t e d from a cause o t h e r t h a n mitral stenosis. Perhaps the most c o m m o n problem to mimic mitral stenosis is a left atrial mass obstructing the inflow tract, such as a left atrial m y x o m a or atrial thrombi. Factors which suggest t h a t a diastolic r u m b l e m a y be e m a n a t i n g from a left atrial mass
800
are: (1) a history of s y n c o p e - s y n c o p e is rare in mitral stenosis; (2) positional changes in symptoms or signs; (3) i n t e r m i t t e n t s y m p t o m s or signs; (4) poor symptom-sign c o r r e l a t i o n - a p a t i e n t with no s y m p t o m s m a y be f o u n d to have an $3 h e a r t sound mimicking an opening snap which occurs very close to the second h e a r t sound; (5) radiographic finding of n o r m a l left atrial size and normal p u l m o n a r y vasculature in a patient with a long-standing diastolic m u r m u r ; (6) advanced age at onset of s y m p t o m s in a p a t i e n t w i t h o u t a previous history of r h e u m a t i c fever or r h e u m a t i c heart disease; and (7) history of peripheral embolism as a presenting c o m p l a i n t in a previously a s y m p t o m a t i c patient. I t is also possible, however, t h a t a left atrial mass (particularly in the case of left atrial thrombi) a n d mitral stenosis m a y occur simultaneously. It is clear t h a t a n u m b e r of the factors mentioned above were present in this patient's history. She presented with syncope; had interm i t t e n t l y heard diastolic m u r m u r s and third h e a r t sounds; did not have t r u e s y m p t o m s until the age of 80; and had a h i s t o r y of a cerebral ischemic episode from w h i c h she recovered extremely rapidly, suggesting the possibility t h a t the episode e m a n a t e d from a cerebral emboius. In addition, her p u l m o n a r y vasculature was n o r m a l and did not suggest mitral stenosis, and she had a normal-sized left atrium. T h e patient's E C G was n o r m a l with the exce p• tion of the atrial fibrillation and the one episode of normal sinus r h y t h m d e m o n s t r a t e d normalsize P waves with a prolonged P R interval. This leads us to consider the possibility t h a t the p a t i e n t had a left atrial mass, and the most likely cause of a left atrial mass would be a left atrial myxoma. T h e age distribution of left atrial m y x o m a e has not been extensively d o c u m e n t e d in the literature. In personal communications with Dr. J o h n Fenoglio of the Armed Forces Institute of P a t h o l o g y (AFIP), I have been assured t h a t there is no selective age distribution and t h a t atrial m y x o m a s have been discovered in people in their 80's. Characteristic of patients above 60 years old with atrial m y x o m a was t h a t the tumors were often missed clinically during life. Of interest, the most c o m m o n s y m p t o m s were congestive heart failure and syncope. Emboli were also quite f r e q u e n t with cerebral emboli being the most common. Very few of the
June, 1976, Vol. 91, No. 6
CPC-Mitral stenosis and left atrial ball thrombus
Fig. 3. Dilated and thick-walled left atrium with the spherical ball thrombus lifted out from the bottom of the "cup" to show a stenotic mitral valve with "fish-mouth" deformity.
p a t i e n t s in the A F I P series died a sudden death, b u t sudden d e a t h has been r e p o r t e d in the p a s t by others.~ 3 I t is also of interest t h a t atrial m y x o m a s need not h a v e c a t a s t r o p h i c clinical courses a n d a r e p o r t in the literature of a p a t i e n t followed for 43 y e a r s who was found to h a v e an atrial m y x o m a was r e p o r t e d before the a d v e n t of surgical t h e r a p y for this2 M y p r e l i m i n a r y clinical diagnosis is, therefore, a left atrial m a s s p r o b a b l y a left atrial m y x o m a p r o d u c i n g inflow tract obstruction to the left ventricle. T h e n e x t question is w h a t was t h e t e r m i n a l episode and this is also difficult to assess. At the t i m e when the p a t i e n t was observed to h a v e a pulse of 32 per m i n u t e , despite the fact t h a t her E C G showed a v e n t r i c u l a r r a t e of 80 or m o r e per minute, the p a t i e n t was alert, cooperative, a n d in no a p p a r e n t distress. This suggests t h a t the m o r e obvious conclusion of inflow t r a c t o b s t r u c t i o n m a y be over simplified. I t would seem t h a t , were t h e m i t r a l valve being occluded sufficiently, so t h a t only 32 palpable pulses could occur out of 80 v e n t r i c u l a r c o n t r a c t i o n s per minute, t h e r e w o u l d be m a r k e d elevation of left atrial pressure a n d the p a t i e n t would be s h o r t of breath. T h e question also arises as to why did this w o m a n die suddenly r a t h e r t h a n j u s t h a v e a s y n c o p a l episode as she
American Heart Journal
h a d previously during t h a t day. I f a p e d u n c u lated left atrial m y x o m a were i n t e r m i t t e n t l y occluding the inflow t r a c t to cause syncope, w h a t changed this f o u r t h and final episode S~ t h a t it resulted in death. One possibility is t h a t the m a s s b e c a m e dislodged f r o m the left atrial wall and h a d t o t a l l y occluded the circulation. This h a s been reported in the p a s t as a Cause of d e a t h in m y x o m a 2 T h e question t h e n arises as to where did the t u m o r b e c o m e lodged. T h e two possibilities are t h a t (1) the t u m o r b e c a m e lodged in the m i t r a l ring, a n d in t h a t case the reported pulse deficit would be difficult to explain, or (2) t h e t u m o r had entered into the left ventricle where it occluded the outflow tract. Physical e x a m i n a t i o n before the p a t i e n t ' s d e a t h d e m o n s t r a t e d a systolic ejection t y p e of m u r m u r and c o m p l e t e absence of previously h e a r d diastolic m u r m u r . I t could be postulated, therefore, t h a t the left atrial m a s s b e c a m e dislodged f r o m the left a t r i u m and descended into the left ventricle where it partially occluded and l a t e r c o m p l e t e l y occluded the left v e n t r i c u l a r outflow tract. Such a n obstructive t u m o r could explain the pulse deficit observed w i t h o u t requiring a s high an elevation of the left atrial pressure. T h e reason for the m a s s not being ejected from the ventricle could result either f r o m
801
Lie a n d E n t m a n
Fig. 4. Bisectedball thrombus showingthe internal laminated structure.
the size of the mass or rigidity of the aortic valve which was hemodynamically insignificant until the present episode.
Clinical diagnoses 1. L e f t atrial m a s s producing a diastolic murmur and syncope, with intermittent episodes of congestive heart failure, p r o b a b l y a left atrial myxoma. 2. Dislodged left atrial mass occluding the systemic circulation, causing sudden death.
Pathologic findings DR. J. T. LIE: Autopsy showed that the patient had died with acute pulmonary congestion and edema. She had bilateral bloody hydrothorax, approximately 200 ml. in each pleural cavity. Although the combined lung weight mass was 1,180 grams, microscopically, there were diffuse engorgement of the alveolar capillaries and marked distention of the air spaces with proteinaceous fluid. In addition, the lungs showed mild fibrosis of the alveolar septa and mild to moderate intimal thickening of the pulmonary arterioles. The pericardium contained 75 ml. of clear fluid. The heart weighed 450 grams. A large spherical mass was palpable, moving freely within the dilated and thick-walled left atrial cavity. On incising the left atrium, it was immediately apparent that a ball thrombus, 3.8 cm. in diameter, had become separated from its attachment to the septal wall of the left atrium and lodged snugly over the mitral opening completely
802
obstructing it (Fig. 3). The mitral valve was both stenotic and incompetent, and showed the "fishm o u t h " deformity produced by fusions of the commissures and fibrous thickening of the valve leaflets. The ball thrombus, completely spherical, had a smooth external surface, and on sectioning, was shown to be composed entirely of old laminated thrombotic material (Fig. 4). The microscopic sections of the atrial and ventricular myocardium showed endocardial thickening and multifocal interstitial fibrosis, but no Aschoff's nodules. There was only mild to moderate coronary atherosclerosis. Apart from moderate generalized visceral congestion, the only other significant finding was histologic evidence of cerebral microinfarcts, involving the basal ganglia and hippocampus.
Anatomical diagnoses 1. Cardiomegaly with moderately severe mitral stenosis and incompetence, presumably of rheumatic origin. 2. Detached ball thrombus of the left atrium, completely obstructing the mitral opening. 3. Acute pulmonary edema and generalized visceral congestion. 4. Pleural and pericardial effusions. 5. Old cerebral microinfarcts.
General comment DR. LIE: Sudden death in this octogenarian woman was brought about by the most unusual occurrence of impaction of the mitral valve by a large ball thrombus. The ball thrombus had
June, 1976, Vol. 91, No. 6
C P C - M i t r a l stenosis and left atrial ball thrombus
a p p a r e n t l y become detached, either spontaneously or incidental to the final resuscitative efforts, and rolled down the cup of the left a t r i a l cavity to block off the mitral opening completely. Thus, m e t a p h o r i c a l l y speaking, we were witnessing a "hole-in-one" t y p e of situation and the o u t c o m e was just as d r a m a t i c and definitively final as it would be on the eighteenth green. Incidentally, the size of the ball t h r o m b u s was almost identical to t h a t of a standard-sized golf ball. T h e term "ball t h r o m b u s " was introduced by Wood, 6 who reported the first case of left atrial ball t h r o m b u s in 1814. He described a 15-year-old girl whose chief complaint was fainting spells, o c c u r r i n g three or four times a day. Clinical suspicion of mitral stenosis was confirmed at autopsy, and a spherical thrombus, 189 inches in diameter, was also found within the left atrium. Macleod, ~ 69 years later, described the first case of right atrial ball thrombus. A l t h o u g h a n t e m o r t e m t h r o m b u s in the atria {especially atrial appendages) is n o t u n u s u a l in a variety of h e a r t diseases, massive left atrial t h r o m b i are u n c o m m o n w i t h o u t mitral valve disease and atrial fibrillation. Ball t h r o m b i are exceedingly rare; R e a d and colleagues ~ were the last to have searched the literature and found a b o u t 60 reported cases. T h e a u t o p s y incidence of ball t h r o m b i is a b o u t one in 2,000 to 3,0002 -H An atrial t h r o m b u s to be designed as "ball t h r o m bus" m u s t meet the rigid criteria as e n u n c i a t e d by Welch ~2 in 1899, t h a t there should be: "(1) entire absence of a t t a c h m e n t and c o n s e q u e n t free mobility; (2) i m p r i s o n m e n t in consequence of excess in the diameter of the t h r o m b u s over t h a t of the first narrowing in the circulatory passage ahead of it; and (3) such consistence and shape t h a t the t h r o m b u s m u s t not of necessity lodge as an embolus in this passage. T h e third point does n o t prejudice the question of the possibility of a ball t h r o m b u s lodging as an embolus; b u t it excludes from the g r o u p . . , detached, shaggy, irregular m a s s e s . . , as m u s t necessarily be c a u g h t at once as emboli in the n a r r o w passage in front." I t is possible t h a t the a p p a r e n t rarity of ball t h r o m b i (as recorded in the literature) is due, in part, to the restrictive criteria of Welch. ~-~ Garvin 1~ considered the distinction between p e d u n c u l a t e d and free ball t h r o m b u s to be entirely academic since b o t h Could produce the same s y m p t o m s . E v a n s and Benson ~ suggested
American Heart J o u r n a l
a b a n d o n i n g the term "ball t h r o m b u s " in favor of the more general designation "mass t h r o m b u s " for a n y thrombus, free or attached, occupying most of the left a t r i u m or for a n y smaller t h r o m b u s t h a t could obstruct the mitral valve. A n t e m o r t e m diagnosis of {right or left) atrial ball t h r o m b u s is certainly possible, t h o u g h it would call for a high index of clinical suspicion. 11"13-~6T h e criteria laid down by Battistini ~7in 1909 still apply: signs of mitral stenosis, changing murmurs, disturbance of the general circulation, postural variations of the pulse, and gangrene o f the lower extremities. In addition, E v a n s and Benson 11 and A b r a m s o n TM emphasized the freq u e n c y of hemiplegia t h a t might be transient in nature. As n o t e d before, the first patient, t h a t of a 15year-old girl described by Wood, ~ was the youngest known, and the oldest was p r o b a b l y the 86year-old w o m a n reported by Garvin2 ~ T h e peak age incidence a m o n g the reported cases was in the fifth decade, with a 3:1 female sex predilection2. 1~ Although mitral stenosis and atrial fibrillation were present in the m a j o r i t y of patients, t h e y are by no m e a n s the absolute prerequisites, s~ ~1 A ball t h r o m b u s has also been described as a complication of infective endocarditis. TM It should also be pointed out t h a t the clinical findings of an atrial ball t h r o m b u s and m y x o m a are similar, and b o t h are a m e n d a b l e to surgery in averting the t h r e a t s of embolic complications and sudden death. We thank Ms. Fran Skinner, C.T.~ASCP)H.T., for the excellent gross photography of Figs. 3 and 4. REFERENCES
1. Wood.P.: In Diseases of the heart and circulation, ed. 3, Philadelphia. 1968, J. B. Lippincott Company. 2. Greenwood. W. F.: Profile of atrial myxoma, Am. J. Cardiol. 21:367, 1968. 3. Wight, R. P.. McCall, M. M.. and Wenger, N. K.: Primary atrial tumor, Am. J. Cardiol. 11:790. 1963. 4. Strouse, S.: Primary benign tumors of the heart of 43 years' duration. Arch. Intern. Med. 62:401, 1938. 5. Brewin. T. B.: "Myxoma" of the heart: Report of a case in which death occurred as a result of detachment of the tumor from its pedicle, Guy's Hosp. Rep. 100"278. 1951. 6. Wood.W.: Letter enclosing the history and dissection of a case m which a foreign body was found within the heart. Edinburgh Med. J. 10:50, 1814. 7. Macleod, N.: A movable clot in right auricle, Edinburgh Med. J. 28:696. 1883. 8. Read, J. L.. Porter, R. R Russi, S.. and Kriz. J. R.: Occlusive auricular thrombi. Circulation 12:250. 1955. 9. Cleland, J. B.: Antemortem clots in the chambers of the heart, Med. J. Aust. 2:50. 1936.
803
Lie a n d E n t m a n
10. 11. 12. 13. 14.
-804
Garvin, C. F.: Ball thrombi in the heart, AM. HEART J. 21:371, 1941. Evans, W., and Benson, R.: Mass thrombus of the left auricle, Br. Heart J. 10:39, 1948. Welch, W. H.: Thrombosis, in Allbutt, T. C., editor: A System of Medicine, vol. 6, London, 1899, Macmillan, pp. 720-722. Smithies, F.: Cardiac thrombosis: The clinical and pathologic findings in three cases, J. A. M. A. 53:1347, 1909. Abramson, J. L.: Ball thrombi of the heart, Ann. Clin. Med. 3:327, 1924.
15. Covey, G. W., Crook, R., and Rogers, F. L.: Ball thrombus of the left auricle, Am. J. Med. Sci. 1 75:60, 1928. 16. Wright, I. S, Flynn, J. E., and Duret, K. L.i Ball thrombus in the right auricle with a description of the symptoms produced, AM. HEART J. 27:858, 1944. 17. Battistini, F.: Due casi di thrombosi dell'orecchietta sinistra diagnostica in vita, Gior. Accad. Med. Torino 4 set., 15:313, 1909. 18. Radding, R. S.: Ball thrombus of the right auricle, Am. J. Med. 1 1:653, 1951.
June, 1976, Vol. 91, No. 6
Case presentation An 83-year-old woman was brought to the hospital on Aug. 16, 1973, by her daughter, after having "passed out" three times on the day of admission. The daughter related t h a t each of the syncopal episodes was sudden in onset and lasted only a few seconds, and that the patient had no seizure activity, although she was incontinent of urine. The patient had been reasonably well all her life. She had a vague history of hypertension, treated intermittently with Reserpine. In addition, diabetes mellitus had been previously diagnosed and she had been taking oral hypoglycemic agents since the age of 75. She had complained of occasional episodes of exertional chest pain t h a t were relieved by nitroglycerin, and, several years previously, mild symptoms of congestive heart failure. Despite this, the patient did not consider herself to be limited in her physical activity on a routine daily basis. In 1970, the patient had an episode of transient aphasia, right hemiparesis, and right hemiparesthesia, but recovered completely from these within a short period of time. She was found to be in atrial fibrillation with a slow ventricular response and was started on a maintenance regime Qf digoxin, 0.125 mg. daily, in addition to oral hypoglycemic drugs and Reserpine. From the Departments of Pathology and Medicine {Cardiologyh Baylor College of Medicine and Ben Taub General Hospital. Texas Medical Center, Houston, Texas. Supported in part by United States Public Health Service Grant HL17269 from the National Heart and Lung Institute. Received for publication March 8, 1976. Reprint requests: J. T. Lie, M.D., Department of Pathology, Baylor College of Medicine, 1200 Moursund. Houston. Texas 77025. *Howard Hughes Medical Investigator.
798
Fig. 1. Chest roentgenogramtaken on Feb. 27. 1972. some 18 months before death, showing slight cardiomegalyand interstitial pulmonary edema.
She was next seen on Feb. 22. 1972, complaining of mild dyspnea on exertion and a cough. Physical examination revealed wheezing and rfiles in the lungs, but no elevation in jugular venous pressure. Cardiac examination was negative. Chest roentgenogram showed mild cardiomegaly and interstitial pulmonary edema (Fig. 1), and the electrocardiogram (ECG) showed slow atrial fibrillation as before. On routine follow-up a month later, the patient's chest roentgenogram was clear and she was asymptomatic. At that
June, 1976, Vol. 91, No. 6, pp. 798-804
C P C - M i t r a l stenosis a n d left atrial ball thrombus
Fig. 2. ECG taken on Aug. 16, 1973, the day of death, showing atrial fibrillation with a ventricular response of 80 per minute.
t i m e the cardiac e x a m i n a t i o n revealed a systolic ejection m u r m u r , but was otherwise u n r e m a r k able. T h e p a t i e n t c o n t i n u e d to do well and ret u r n e d for a routine hospital visit on Aug. 23, 1972. and was found again to be in atrial fibrillation with a h e a r t rate of 60 per minute. Cardiac e x a m i n a t i o n at t h a t t i m e described a G r a d e 2/4 diastolic r u m b l e h e a r d best with the p a t i e n t in the left lateral decubitus position. In addition, a third heart sound was h e a r d which was described as an opening snap. T h e p a t i e n t was referred to the cardiac clinic with the diagnosis of possible r h e u m a t i c h e a r t disease. Chest r o e n t g e n o g r a m a t this t i m e was again essentially negative. T h e p a t i e n t was seen 2 m o n t h s later in the cardiac clinic, where a physical e x a m i n a t i o n was completely n o r m a l a n d no m u r m u r s could be h e a r d by several cardiologists. In March, 1973, the p a t i e n t h a d a n o t h e r episode of d y s p n e a a n d she
American Heart Journal
was found to be in n o r m a l sinus r h y t h m with P R i n t e r v a l of 0.24. A chest r o e n t g e n o g r a m at t h a t t i m e showed some mild venous congestion, but no f r a n k p u l m o n a r y edema. T h e p a t i e n t r e t u r n e d a week later for a r o u t i n e visit and was a s y m p t o matic. In June, 1973, the p a t i e n t was seen in the h o s p i t a l and for the first time since August, 1972, the diastolic r u m b l e was heard along with an a u g m e n t e d first h e a r t sound. No opening snap or third h e a r t sound was h e a r d during this visit. T h e clinical impression a t the time was t h a t the p a t i e n t p r o b a b l y h a d mild r h e u m a t i c mitral stenosis, and because of her age, no f u r t h e r studies were indicated. T h e final episode b e g a n on Aug. 16, 1973, when sync0pal a t t a c k s occurring earlier t h a t d a y b r o u g h t the p a t i e n t to the hospital e m e r g e n c y room, where she experienced no f u r t h e r s y m p toms. On admission, her blood pressure was
799
Lie and Entman
140/100 mm. Hg and she h a d a pulse rate of 90 per minute. However, some time during the course of her time in the emergency room, a peripheral pulse of 32 per m i n u t e was noted. S e r u m electrolytes were n o r m a l and the ECG revealed atrial fibrillation with a ventricular response of 80 per m i n u t e (Fig. 2). T h e p a t i e n t claimed t h a t she felt perfectly well, and was instructed to stop taking digoxin for 2 days and to r e t u r n to the hospital for a follow-up evaluation. W h e n she was a b o u t to enter her car in the hospital parking lot, she experienced a n o t h e r sudden syncopal episode, and was taken back to the hospital as she was recovering. By the time she arrived in the emergency room, however, she was comatose and found to be in cardiorespiratory arrest with no peripheral pulses. An E C G showed narrow QRS complexes at 20 per minute, and cardiopulm o n a r y resuscitation was applied. T h i r t y minutes later, the ECG had become virtually a flat line. and she was cyanotic. S p o n t a n e o u s respirations were weak and i n t e r m i t t e n t , and the pupils were fixed in the mid position. J u g u l a r venous pulse was fully distended and the h e a r t rate varied from 100 to 150 beats per minute. She died shortly thereafter. Clinical discussion DR. M. L. ENTMAN: This is the story of a w o m a n who was found to have the late onset of a diastolic rumble, diagnosed as probably of rheumatic origin. It would be extremely u n u s u a l for a w o m a n to remain a s y m p t o m a t i c from mitral stenosis until her 80's and not have signs of left atrial enlargement, a past history of congestive h e a r t failure, or a past history of r h e u m a t i c h e a r t disease. It has been estimated t h a t the average time between the onset of r h e u m a t i c h e a r t disease and the onset of s y m p t o m a t i c mitral stenosis is 20 to 30 years 1 which would place this lady's episode of r h e u m a t i c fever (if t h e r e were such an episode) in her sixth decade. Although all things are possible, we must therefore consider the possibility t h a t the diastolic m u r m u r in this case e m a n a t e d from a cause o t h e r t h a n mitral stenosis. Perhaps the most c o m m o n problem to mimic mitral stenosis is a left atrial mass obstructing the inflow tract, such as a left atrial m y x o m a or atrial thrombi. Factors which suggest t h a t a diastolic r u m b l e m a y be e m a n a t i n g from a left atrial mass
800
are: (1) a history of s y n c o p e - s y n c o p e is rare in mitral stenosis; (2) positional changes in symptoms or signs; (3) i n t e r m i t t e n t s y m p t o m s or signs; (4) poor symptom-sign c o r r e l a t i o n - a p a t i e n t with no s y m p t o m s m a y be f o u n d to have an $3 h e a r t sound mimicking an opening snap which occurs very close to the second h e a r t sound; (5) radiographic finding of n o r m a l left atrial size and normal p u l m o n a r y vasculature in a patient with a long-standing diastolic m u r m u r ; (6) advanced age at onset of s y m p t o m s in a p a t i e n t w i t h o u t a previous history of r h e u m a t i c fever or r h e u m a t i c heart disease; and (7) history of peripheral embolism as a presenting c o m p l a i n t in a previously a s y m p t o m a t i c patient. I t is also possible, however, t h a t a left atrial mass (particularly in the case of left atrial thrombi) a n d mitral stenosis m a y occur simultaneously. It is clear t h a t a n u m b e r of the factors mentioned above were present in this patient's history. She presented with syncope; had interm i t t e n t l y heard diastolic m u r m u r s and third h e a r t sounds; did not have t r u e s y m p t o m s until the age of 80; and had a h i s t o r y of a cerebral ischemic episode from w h i c h she recovered extremely rapidly, suggesting the possibility t h a t the episode e m a n a t e d from a cerebral emboius. In addition, her p u l m o n a r y vasculature was n o r m a l and did not suggest mitral stenosis, and she had a normal-sized left atrium. T h e patient's E C G was n o r m a l with the exce p• tion of the atrial fibrillation and the one episode of normal sinus r h y t h m d e m o n s t r a t e d normalsize P waves with a prolonged P R interval. This leads us to consider the possibility t h a t the p a t i e n t had a left atrial mass, and the most likely cause of a left atrial mass would be a left atrial myxoma. T h e age distribution of left atrial m y x o m a e has not been extensively d o c u m e n t e d in the literature. In personal communications with Dr. J o h n Fenoglio of the Armed Forces Institute of P a t h o l o g y (AFIP), I have been assured t h a t there is no selective age distribution and t h a t atrial m y x o m a s have been discovered in people in their 80's. Characteristic of patients above 60 years old with atrial m y x o m a was t h a t the tumors were often missed clinically during life. Of interest, the most c o m m o n s y m p t o m s were congestive heart failure and syncope. Emboli were also quite f r e q u e n t with cerebral emboli being the most common. Very few of the
June, 1976, Vol. 91, No. 6
CPC-Mitral stenosis and left atrial ball thrombus
Fig. 3. Dilated and thick-walled left atrium with the spherical ball thrombus lifted out from the bottom of the "cup" to show a stenotic mitral valve with "fish-mouth" deformity.
p a t i e n t s in the A F I P series died a sudden death, b u t sudden d e a t h has been r e p o r t e d in the p a s t by others.~ 3 I t is also of interest t h a t atrial m y x o m a s need not h a v e c a t a s t r o p h i c clinical courses a n d a r e p o r t in the literature of a p a t i e n t followed for 43 y e a r s who was found to h a v e an atrial m y x o m a was r e p o r t e d before the a d v e n t of surgical t h e r a p y for this2 M y p r e l i m i n a r y clinical diagnosis is, therefore, a left atrial m a s s p r o b a b l y a left atrial m y x o m a p r o d u c i n g inflow tract obstruction to the left ventricle. T h e n e x t question is w h a t was t h e t e r m i n a l episode and this is also difficult to assess. At the t i m e when the p a t i e n t was observed to h a v e a pulse of 32 per m i n u t e , despite the fact t h a t her E C G showed a v e n t r i c u l a r r a t e of 80 or m o r e per minute, the p a t i e n t was alert, cooperative, a n d in no a p p a r e n t distress. This suggests t h a t the m o r e obvious conclusion of inflow t r a c t o b s t r u c t i o n m a y be over simplified. I t would seem t h a t , were t h e m i t r a l valve being occluded sufficiently, so t h a t only 32 palpable pulses could occur out of 80 v e n t r i c u l a r c o n t r a c t i o n s per minute, t h e r e w o u l d be m a r k e d elevation of left atrial pressure a n d the p a t i e n t would be s h o r t of breath. T h e question also arises as to why did this w o m a n die suddenly r a t h e r t h a n j u s t h a v e a s y n c o p a l episode as she
American Heart Journal
h a d previously during t h a t day. I f a p e d u n c u lated left atrial m y x o m a were i n t e r m i t t e n t l y occluding the inflow t r a c t to cause syncope, w h a t changed this f o u r t h and final episode S~ t h a t it resulted in death. One possibility is t h a t the m a s s b e c a m e dislodged f r o m the left atrial wall and h a d t o t a l l y occluded the circulation. This h a s been reported in the p a s t as a Cause of d e a t h in m y x o m a 2 T h e question t h e n arises as to where did the t u m o r b e c o m e lodged. T h e two possibilities are t h a t (1) the t u m o r b e c a m e lodged in the m i t r a l ring, a n d in t h a t case the reported pulse deficit would be difficult to explain, or (2) t h e t u m o r had entered into the left ventricle where it occluded the outflow tract. Physical e x a m i n a t i o n before the p a t i e n t ' s d e a t h d e m o n s t r a t e d a systolic ejection t y p e of m u r m u r and c o m p l e t e absence of previously h e a r d diastolic m u r m u r . I t could be postulated, therefore, t h a t the left atrial m a s s b e c a m e dislodged f r o m the left a t r i u m and descended into the left ventricle where it partially occluded and l a t e r c o m p l e t e l y occluded the left v e n t r i c u l a r outflow tract. Such a n obstructive t u m o r could explain the pulse deficit observed w i t h o u t requiring a s high an elevation of the left atrial pressure. T h e reason for the m a s s not being ejected from the ventricle could result either f r o m
801
Lie a n d E n t m a n
Fig. 4. Bisectedball thrombus showingthe internal laminated structure.
the size of the mass or rigidity of the aortic valve which was hemodynamically insignificant until the present episode.
Clinical diagnoses 1. L e f t atrial m a s s producing a diastolic murmur and syncope, with intermittent episodes of congestive heart failure, p r o b a b l y a left atrial myxoma. 2. Dislodged left atrial mass occluding the systemic circulation, causing sudden death.
Pathologic findings DR. J. T. LIE: Autopsy showed that the patient had died with acute pulmonary congestion and edema. She had bilateral bloody hydrothorax, approximately 200 ml. in each pleural cavity. Although the combined lung weight mass was 1,180 grams, microscopically, there were diffuse engorgement of the alveolar capillaries and marked distention of the air spaces with proteinaceous fluid. In addition, the lungs showed mild fibrosis of the alveolar septa and mild to moderate intimal thickening of the pulmonary arterioles. The pericardium contained 75 ml. of clear fluid. The heart weighed 450 grams. A large spherical mass was palpable, moving freely within the dilated and thick-walled left atrial cavity. On incising the left atrium, it was immediately apparent that a ball thrombus, 3.8 cm. in diameter, had become separated from its attachment to the septal wall of the left atrium and lodged snugly over the mitral opening completely
802
obstructing it (Fig. 3). The mitral valve was both stenotic and incompetent, and showed the "fishm o u t h " deformity produced by fusions of the commissures and fibrous thickening of the valve leaflets. The ball thrombus, completely spherical, had a smooth external surface, and on sectioning, was shown to be composed entirely of old laminated thrombotic material (Fig. 4). The microscopic sections of the atrial and ventricular myocardium showed endocardial thickening and multifocal interstitial fibrosis, but no Aschoff's nodules. There was only mild to moderate coronary atherosclerosis. Apart from moderate generalized visceral congestion, the only other significant finding was histologic evidence of cerebral microinfarcts, involving the basal ganglia and hippocampus.
Anatomical diagnoses 1. Cardiomegaly with moderately severe mitral stenosis and incompetence, presumably of rheumatic origin. 2. Detached ball thrombus of the left atrium, completely obstructing the mitral opening. 3. Acute pulmonary edema and generalized visceral congestion. 4. Pleural and pericardial effusions. 5. Old cerebral microinfarcts.
General comment DR. LIE: Sudden death in this octogenarian woman was brought about by the most unusual occurrence of impaction of the mitral valve by a large ball thrombus. The ball thrombus had
June, 1976, Vol. 91, No. 6
C P C - M i t r a l stenosis and left atrial ball thrombus
a p p a r e n t l y become detached, either spontaneously or incidental to the final resuscitative efforts, and rolled down the cup of the left a t r i a l cavity to block off the mitral opening completely. Thus, m e t a p h o r i c a l l y speaking, we were witnessing a "hole-in-one" t y p e of situation and the o u t c o m e was just as d r a m a t i c and definitively final as it would be on the eighteenth green. Incidentally, the size of the ball t h r o m b u s was almost identical to t h a t of a standard-sized golf ball. T h e term "ball t h r o m b u s " was introduced by Wood, 6 who reported the first case of left atrial ball t h r o m b u s in 1814. He described a 15-year-old girl whose chief complaint was fainting spells, o c c u r r i n g three or four times a day. Clinical suspicion of mitral stenosis was confirmed at autopsy, and a spherical thrombus, 189 inches in diameter, was also found within the left atrium. Macleod, ~ 69 years later, described the first case of right atrial ball thrombus. A l t h o u g h a n t e m o r t e m t h r o m b u s in the atria {especially atrial appendages) is n o t u n u s u a l in a variety of h e a r t diseases, massive left atrial t h r o m b i are u n c o m m o n w i t h o u t mitral valve disease and atrial fibrillation. Ball t h r o m b i are exceedingly rare; R e a d and colleagues ~ were the last to have searched the literature and found a b o u t 60 reported cases. T h e a u t o p s y incidence of ball t h r o m b i is a b o u t one in 2,000 to 3,0002 -H An atrial t h r o m b u s to be designed as "ball t h r o m bus" m u s t meet the rigid criteria as e n u n c i a t e d by Welch ~2 in 1899, t h a t there should be: "(1) entire absence of a t t a c h m e n t and c o n s e q u e n t free mobility; (2) i m p r i s o n m e n t in consequence of excess in the diameter of the t h r o m b u s over t h a t of the first narrowing in the circulatory passage ahead of it; and (3) such consistence and shape t h a t the t h r o m b u s m u s t not of necessity lodge as an embolus in this passage. T h e third point does n o t prejudice the question of the possibility of a ball t h r o m b u s lodging as an embolus; b u t it excludes from the g r o u p . . , detached, shaggy, irregular m a s s e s . . , as m u s t necessarily be c a u g h t at once as emboli in the n a r r o w passage in front." I t is possible t h a t the a p p a r e n t rarity of ball t h r o m b i (as recorded in the literature) is due, in part, to the restrictive criteria of Welch. ~-~ Garvin 1~ considered the distinction between p e d u n c u l a t e d and free ball t h r o m b u s to be entirely academic since b o t h Could produce the same s y m p t o m s . E v a n s and Benson ~ suggested
American Heart J o u r n a l
a b a n d o n i n g the term "ball t h r o m b u s " in favor of the more general designation "mass t h r o m b u s " for a n y thrombus, free or attached, occupying most of the left a t r i u m or for a n y smaller t h r o m b u s t h a t could obstruct the mitral valve. A n t e m o r t e m diagnosis of {right or left) atrial ball t h r o m b u s is certainly possible, t h o u g h it would call for a high index of clinical suspicion. 11"13-~6T h e criteria laid down by Battistini ~7in 1909 still apply: signs of mitral stenosis, changing murmurs, disturbance of the general circulation, postural variations of the pulse, and gangrene o f the lower extremities. In addition, E v a n s and Benson 11 and A b r a m s o n TM emphasized the freq u e n c y of hemiplegia t h a t might be transient in nature. As n o t e d before, the first patient, t h a t of a 15year-old girl described by Wood, ~ was the youngest known, and the oldest was p r o b a b l y the 86year-old w o m a n reported by Garvin2 ~ T h e peak age incidence a m o n g the reported cases was in the fifth decade, with a 3:1 female sex predilection2. 1~ Although mitral stenosis and atrial fibrillation were present in the m a j o r i t y of patients, t h e y are by no m e a n s the absolute prerequisites, s~ ~1 A ball t h r o m b u s has also been described as a complication of infective endocarditis. TM It should also be pointed out t h a t the clinical findings of an atrial ball t h r o m b u s and m y x o m a are similar, and b o t h are a m e n d a b l e to surgery in averting the t h r e a t s of embolic complications and sudden death. We thank Ms. Fran Skinner, C.T.~ASCP)H.T., for the excellent gross photography of Figs. 3 and 4. REFERENCES
1. Wood.P.: In Diseases of the heart and circulation, ed. 3, Philadelphia. 1968, J. B. Lippincott Company. 2. Greenwood. W. F.: Profile of atrial myxoma, Am. J. Cardiol. 21:367, 1968. 3. Wight, R. P.. McCall, M. M.. and Wenger, N. K.: Primary atrial tumor, Am. J. Cardiol. 11:790. 1963. 4. Strouse, S.: Primary benign tumors of the heart of 43 years' duration. Arch. Intern. Med. 62:401, 1938. 5. Brewin. T. B.: "Myxoma" of the heart: Report of a case in which death occurred as a result of detachment of the tumor from its pedicle, Guy's Hosp. Rep. 100"278. 1951. 6. Wood.W.: Letter enclosing the history and dissection of a case m which a foreign body was found within the heart. Edinburgh Med. J. 10:50, 1814. 7. Macleod, N.: A movable clot in right auricle, Edinburgh Med. J. 28:696. 1883. 8. Read, J. L.. Porter, R. R Russi, S.. and Kriz. J. R.: Occlusive auricular thrombi. Circulation 12:250. 1955. 9. Cleland, J. B.: Antemortem clots in the chambers of the heart, Med. J. Aust. 2:50. 1936.
803
Lie a n d E n t m a n
10. 11. 12. 13. 14.
-804
Garvin, C. F.: Ball thrombi in the heart, AM. HEART J. 21:371, 1941. Evans, W., and Benson, R.: Mass thrombus of the left auricle, Br. Heart J. 10:39, 1948. Welch, W. H.: Thrombosis, in Allbutt, T. C., editor: A System of Medicine, vol. 6, London, 1899, Macmillan, pp. 720-722. Smithies, F.: Cardiac thrombosis: The clinical and pathologic findings in three cases, J. A. M. A. 53:1347, 1909. Abramson, J. L.: Ball thrombi of the heart, Ann. Clin. Med. 3:327, 1924.
15. Covey, G. W., Crook, R., and Rogers, F. L.: Ball thrombus of the left auricle, Am. J. Med. Sci. 1 75:60, 1928. 16. Wright, I. S, Flynn, J. E., and Duret, K. L.i Ball thrombus in the right auricle with a description of the symptoms produced, AM. HEART J. 27:858, 1944. 17. Battistini, F.: Due casi di thrombosi dell'orecchietta sinistra diagnostica in vita, Gior. Accad. Med. Torino 4 set., 15:313, 1909. 18. Radding, R. S.: Ball thrombus of the right auricle, Am. J. Med. 1 1:653, 1951.
June, 1976, Vol. 91, No. 6
