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Profile of atrial myxoma
Profile of Atria1 Mvxoma WILLIAM
FREDERICK GREENWOOD, Toronto,
M.D.*
Canada
view of the literature, to designate the wide spectrum of disease which these tumors can mimic; to try to determine how myxoma differs clinically from the diseases it mimics, and to decide under what conditions one should suspect myxoma and obtain the appropriate angiogram.
YXOMA, a benign intracavitary tumor of the heart, is rare. By 1965 about 350 cases had been reported.’ It is important because it can be abolished by surgical therapy and is usually rapidly fatal if unrecognized and untreated. Diagnosis by angiocardiography seems to be quite accurate; in most of the cases in which myxoma was diagnosed before operation, it was demonstrated in this way. However, false positives2 and false negatives3 have been observed. The lesion must be suspected before the appropriate angiogram is made. The clinical diagnosis was first made by angiography in 1951 ,4 and the first successful surgical excisions were performed in 1955.5,6 A wider use of angiocardiography in the routine investigation of valve lesions before surgery can be expected to increase the number of myxomas found preoperatively; the practice of using cardiopulmonary bypass for all mitral commissurotomies’ or having it available promptly to surgeons performing closed mitral commissurotomies should increase the number of successful resections among those cases found unexpectedly at 0peration.s One important factor in attaining recognition and cure will be the painfully acquired habit of doubting the obvious, a trait of physicians who practice under conditions in which successes and failures are regularly exposed by colleagues in surgery or pathology. No one person can hope to see a sufficient number of these tumors to appreciate from his own experience the many ways in which they manifest themselves. In the past 10 years many authors,g-27 after reporting a few cases of their own, reviewing a group of the reported cases and, in some instances, using their imagination have suggested methods for suspecting the presence of myxoma. The object of this study is, by a critical re-
M
CONSIDERATIONS COMMON TO ALL INTRACAVITARY MYXOMAS The Anatomy of the Lesion: Three quarters of these tumors arise in the left atrium, and nearly all the rest in the right.2s A few, some of which have been successfully removed surgically, have occurred in the ventricles.2g-34 Characteristically, atria1 myxomas arise in or near the fossa ovalis and are pedunculated.3j The pedicle may be short, allowing little movement, or it may be long, allowing the tumor to pass back and forth from atrium to ventricle during the cardiac cycle.2v24*36 Sometimes the tumor has a distinct mark made by the valve ring on its surface, dividing it into distinct atria1 and ventricular segments, thus indicating residence in the ring. It may be solid and spherical or lobulated and have villous projections. These tumors are almost always solitary, but a patient with one large and three small pedunculated tumors in the right atrium and a pedunculated polypoid tumor in the left atrium has been reported by Frankenfeld et a1.37 Kaufman et a1.3s have reported successful surgical removal at one operation of right and left atria1 myxomas which had given rise to both pulmonary and systemic emboli. An 11 year old boy, reported on by Gumming and Finkel,“g had both pulmonary and systemic emboli from a myxoma of the left atrium which extended through the foramen ovale to form a mass 3.5 by 2 by 1 cm. in the right atrium. Gross calcijication is rarely present in myxomas. It has been visualized fluoroscopically in 2
* From the Department of Medicine, University of Toronto, and the Cardiovascular Unit, Toronto General Hospital, Ontario, Canada. Address for reprints: William F. Greenwood, M.D., Cardiovascular Unit, Toronto General Hospital, Toronto 2. Ontario, Canada. VOLUME
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cases of right atria140a4i and 1 of left atria1 myxonla.4? A myxoma from the right atrium showed hemorrhages and some calcification after remova1.43 Relation Between the Anatomy of the Lesion and the Signs and Symptoms: As first pointed out by Goodwin,? myxomas show themselves clinically in three ways, (1) by embolization, (2) by obstruction to the flow of blood and (3) by constitutional effects; that is, by producing symptoms and signs of a constitutional nature as well as changes in the blood which can be detected by hematologic or biochemical examination. EMBOLIZATION Emboli arising in patients with myxoma can consist of tumor fragments or thrombus from the surface of the tumor. Occasionally nearly the whole tumor has been observed to break off, thus obstructing the bifurcation of the aorta. Tumors in either the left or right side of the heart may- obstruct blood flow and lead to congestive heart failure; therefore, venous thrombosis and pulmonary embolism, which commonly complicate failure, would be expected to occur in patients with myxoma of either Pulmonary arterial obstruction ocatrium. curred in 13 of 45 cases of left atria1 myxoma reported by Goodwim2 but in only 243,44 of 282df45-8 cases of right atria1 myxoma was pulmonary embolism noted clinically. It is an odd paradox that pulmonary arterial obstruction seems to be commoner in left atria1 myxoma than in right. In right atria1 myxoma arterial unsaturation presumably due to a right to left shunt occasionally occurs11,46,4g (i.e., in 3 of the 28 cases previously referred to). Although one might expect paradoxic embolism occasionally with right atria1 myxoma, to my knowledge it has not so far been reported. Systemic embolism from myxoma has so far been seen in cases of myxoma of the left atrium, in which it occurred in approximately 40 per cent of patients,2~3~23 and of the left ventricle, in which it occurred in 4 of the 5 reported cases.32-34 THE RESULTS OF OBSTRUCTION TO BLOOD FLOW Small tumors, unless they lead to emboli, are usually asymptomatic. As they enlarge they obstruct, interfering with the transfer of blood from pulmonary or systemic veins through the atrium to the ventricle and leading to the signs and symptoms of congestive heart failure.
The tumor may obstruct the atrioventricular valve, or it may nearly fill the atrium, which usually does not become much enlarged probably because it is not diseased. It is interesting that x-ray evidence of left atria1 enlargement present before operation has disappeared after removal of the tumor.* The obstruction is characteristically inexorably progressive, thus giving rise to the statement that these tumors are pathologically benign but clinically malignant.2g Less commonly, a tumor on a pedicle that allows movement may cause intermittent obstruction leading to syncope or sudden death. This condition occurs in less than a quarter of the cases2 t3,23 More rarely,13J*~50 a remarkable remission from dyspnea or established congestive failure presumably due to intermittent obstruction, may occur in the course of the disease. In Gerbode’s cases0 this relief, which lasted 20 months, followed the occurrence of peripheral emboli from which the patient recovered. Murmurs: Obstruction usually leads to the diastolic murmur characteristic of mitral or tricuspid obstruction, but if valve closure is prevented by the tumor a systolic murmur due to regurgitation may be produced. Variation in murmurs with time and with change in position has been noted and stressed by some as an important clue to the possible presence of myxoma . It is well known that the intensity of the murmur of mitral stenosis characteristically is louder when the patient is lying on his left side, and that its intensity increases with activity or when the patient comes out of congestive failure. To arouse suspicion, therefore, variation in murmurs with time or position must be unlike the variation found in mitral disease. This variability is not often mentioned in the case reports reviewed, although it often appears in the list of possible clues to the presence of a myxoma. Obviously the fallibility of the human memory, even aided by notes, would limit the usefulness of variation in murmurs as a clue even if it were to occur with any frequency. The situation reminds one of the variable murmurs of bacterial endocarditis, which are so often talked about and so seldom seen. Friction Rub: In one reported case of myxoma of the right atrium, a loud systolic crunching noise at the lower end of the sternum with an elevated venous pressure and constitutional manifestations led to the diagnosis of tuberTHE
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Profile
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clllosis pericarditis.44 In a second patient with a right atria1 myxoma that was successfully removed under hypothermia, a loud “pleuropericardial friction rub” persisted throughout his illness.4” In Frankenfeld’s3’ patient with bilateral myxomas a to-and-fro crunching rub at the left sternal border was heard. In 2 other patients with right atria1 myxoma pericardial friction rubs were noted.51s52 These odd noises may have resulted from the tumor rubbing on the endocardial surface of the heart during the cardiac cycle. I have seen a report of a similar noise in only 1 case of left atria1 myxoma.53 Perhaps because of the posterior position of the left atrium a rub caused by a tumor is seldom heard. Opening snaps have been heard and recorded in patients with left atria1 myxoma.36t54-6 Wassermil et a1.56 have noted in phonocardiograms of 3 patients with left atria1 myxoma an accentuated and a delayed first sound (QS interval) and accentuated pulmonary valve clos-’ ure. They have noted presystolic mitral murmurs in 2 of their 3 patients and conclude that the findings are the same as in mitral stenosis. However, mitral murmurs were absent in 1 case, intermittent or faint in 1 and apparently fairly obvious in only 1. Pitt et a1.36 have recorded simultaneously phonocardiograms, left ventricular pressure tracings and cineangiograms in 2 patients with left atria1 myxoma. With ventricular contraction the tumor entered the left atrium, and at this time large left atria1 v waves occurred in the absence of mitral regurgitation, and a notch occurred on the rising record of left ventricular pressure. These events corresponded with a loud first heart sound. An opening snap occurred after the mitral valve opened and was synchronous with checking the excursion of the tumor once it was in the left ventricle. Thus, these sounds, although clinically indistinguishable from those produced by mitral stenosis, appear to be due to tumor movement in these patients and may not originate at the mitral valve. Goodwin2 in his review of 45 cases observed by members of the British Cardiac Society states that in the typical patient the murmurs were atypical or hard to hear. This is probably as near as one can come to a helpful statement about the physical findings in left atria1 myxoma. The ausculatory jkdings in 25 reported cases of right atria1 myxoma24~26~43J4,48 are shown in Table I. It is apparent that 80 per cent of VOLUME
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Myxoma
369 TABLE
The
I
Findings on Auscultation in 25 Reported of Right Atria1 Myxoma24~s6~437bP.1Y
Casey
Diastolic rn~rrn~l~ only Systolic and diastolic rnwrnw~ Murmurs and a friction rllb Systolic mwmur only Friction rub only No mumnm or rllbs Total caged analyzed
patients had murmurs, 20 per cent had pericardial friction rubs and only 12 per cent had no murmurs or rubs. CONSTITUTIONAL MYXOMA
EFFECTS OF THE
OF
HEART
From a review of individual published cases, it is impossible to form any reliable opinion about the incidence of inconspicuous constitutional signs and symptoms. However, Goodwin2 sent a questionnaire to the members of the British Cardiac Society about their cases of left atria1 myxoma. The answers he received enabled him to determine that 40 of the 45 patients (89 per cent) represented by this survey had one of the following five constitutional manifestations : fever (53 per cent), raised sedimentation rate (69 per cent), weight loss (36 per cent), anemia (44 per cent) and abnormal serum proteins (48 per cent). He also showed that these manifestations occurred much more frequently in patients with myxoma than in those who had uncomplicated mitral stenosis. However, mitral stenosis is often complicated by pulmonary infection, pulmonary infarction, active rheumatic fever, severe chronic passive congestion of liver, bland thrombosis in leg veins and bacterial endocarditis. It may also exist with other diseases that can cause COIItitutional effects. In searching for the cause of constitutional manifestations in a patient with heart disease it seems apparent that one must add myxoma to the list of possibilities. Fever,22 ,43 elevation of sedimentation rate,22 .24,43,44 elevation of gamma globulin57 and weight loss 48 have been reported in association with myxomas of the right atrium and right ventricle. However, right atria1 myxomas, unlike those on the left side, tend to have a high hemoglobin,24 which is sometimes46 but not always associated with arterial hypoxia at rest. The arterial hypoxia occasionally observed in
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right atria1 In)-xolrla may be due to a shunt through a dilated foramen ovale,4fi or through a coexisting atria1 septal defect.4” Clubbing has occurred in both right46 and left-sided rnyxomas,2 Al in the former instance with arterial unsaturation. Raynaud’s phenomenon has occurred as the initial symptom in a 15 year old gir1.58 There are isolated reports of other constitutional and hematologic effects of myxoma. Vuopia and NikkilZ 5g have reported a case of mitral stenosis with left atria1 myxoma and hemolytic anemia probably due to mechanical destruction of blood by turbulence. This patient had a hemoglobin of 6.4 gm./lOO ml. with 16 per cent reticulocytes, a white blond count up to 32,000 per cu. mm. and thrombocytopenia (platelets 2,600 to 34,000 per cu. mm.). Bizarre poikilocytes were observed in the smear. The myxoma was found at postmortem examination. Willman et a1.46 have described a woman with striking clubbing of the fingers, heart failure, arterial unsaturation (88 per cent decreasing to 66 per cent after 30 minutes supine), purpuric spots and a platelet count of 30,000 per cu. mm. The platelets did not increase after administration of cortisone but within three days after removal of a right atria1 myxoma the count rose to 230,000 and the cyanosis disappeared. Thus it appears that myxorna can cause increased destruction of both red blood cells and platelets. This fact suggests that minor degrees of hemolysis and an increased platelet turnover might be present in many other cases if one looked for it. On the other hand, in the case of Levinson and Kincaid57 the hematocrit was 54 per cent and the platelet count 1,386 per cu. mm. before removal of a right atria1 myxoma. The C-reactive protein has been elevated (2+ to 4f in 3 cases) .37 J* s4* White blood counts of over 18,000 per cu. mm. have occurred.18JgJ2~30~~0 It should be worthwhile examining the blood for elevations of transaminases if multiple small emboli to muscles occur and account for some of the constitutional manifestations as suggested by Goodwin.2 Elevation of serum glutamic oxalacetic transaminase to 188 units has been reported in a case of left atria1 myxoma.60 For the same reason microscopic hematuria should be looked for although it has not been reported. Roper et al.‘jl have reported 2 cases of left atria1 myxoma associated with fibroadenoma In each case the secof the breast in women.
tions of the breast showed myxomatous stronta in the fibroadenomas. They suggest that there may be rnyxomatous change in 111ore than one: organ system. A 23 year old male patient,6” admitted to ,i U. S. Army Hospital in Nuremberg, had a fulminating pneumonia and died within 30 hours of the onset of illness. At postmortem examination a left atria1 myxoma 3 by 2 by 2 cm. Intimal atheroma and hemosiderowas found. sis of the lungs suggested pre-existing pulmonary hypertension. They compared the rapidly deteriorating condition with that of patients with rheumatic heart disease observed by Louria et a1.63 during an influenza pandemic. However, no other suggestion has been made that patients with myxoma have an increased susceptibility to infection. The factors causing constitutional disturHemorrhage and bances are not entirely clear. degeneration within the turnor13 or multiple small emboli to muscles2 have been suggested. An immune response to fragments of tumor released into the circulation has been invoked as a possible cause of the increase in gamma globulins.10 Currey et al. 64 have reported immunologic studies, before and after operation, in a patient with a right atria1 myxoma and conspicuous constitutional manifestations that Antibodies cleared after removal of the tumor. to myxoma were not demonstrated, but antibodies to fresh human heart muscle were present before operation, the titer dropping from 1 : 120 to 1 :40 four months after operation. The) have previously demonstrated these antibodies in a high percentage of patients with postcardiotomy and postmyocardial infarction syndromes. They suggest, “It is possible that an intracardiac myxoma may initiate and maintain an autoimmune state analogous to that seen after cardiotomy or myocardial infarction.” DIAGNOSIS MYXOMAS
OF LEFT AND RIGHT BY ANGIOCARDIOGRAPHY
ATRIAL
Left Atrial Myxoma: With modern equipment and contrast media, selective injection of the radiopaque dye into the pulmonary artery with a Gidlund compressed-air syringe and the use of cineangiography with 30 or more frames a second, the pictures of the left atrium obtained now are so good that it seems unlikely that false positives or negatives would now plague us. In 1958 a patient with a myxoma that was not detected by angiography was described.51 False positives have also been deTHE
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Profile of Atria1 Myxonla
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scribed.2a3 In 1 of these patients the error was
elusion of a systemic artery or a series of such
ascribed to blood from the pulmonary veins diluting the contrast medium.2 In the second3 the injection was made into the left atrium, and it swirled around, thus presenting an appearance that caused some concern about the presence of a filling defect. At operation with a pump standby the patient had mitral stenosis. Clot and myxoma can theoretically be confused, but to my knowledge have not been. The movement of a myxoma is unmistakable, if it is observed angiographically.2~24~36 Right Atria1 Myxoma: In this case, the injection is made into one of the venae cavae or the right atrium. The former is probably preferable. A technically satisfactory angiogram should now be possible, and for the reasons cited above, it seems unlikely that errors in diagnosis would occur with modern technics. The Use of Ultra Sound in the Diagnosis of Atria1 Myxoma: Sega1,‘j5 states that “atria1 thrombi or myxoma have occasionally been suspected in the preoperative evaluation of patients using ultrasonic technics. However, much more experience is necessary to determine the accuracy of ultra sound for detecting these conditions.”
occlusions,
DIFFERENTIAL DIAGNOSIS OF LEFT ATRIAL MYXOMA
In Patients Presenting with Obstruction, Emboli and Constitutional Manifestations: In patients presenting with a combination of these three types of symptoms and signs one should consider the possibility of left atria1 myxoma, as well as mitral disease complicated by bacterial endocarditis, or some other infection, including active rheumatic disease. Consistently negative blood cultures do not exclude bacterial endocarditis, but when combined with a lack of response to antibiotics one should probably obtain an angiocardiogram to exclude myxoma. The presence of positive blood cultures is most unusual in myxoma but has been reported once.6F A history of rheumatic fever or the presence of aortic murmurs makes myxoma unlikely but does not exclude it. If one is dissatisfied with the nature of a suspected infection in a patient considered to have mitral stenosis, one should consider myxoma. In Patients with Emboli Alone: About 45 per cent of left atria1 myxomas give rise to systemic embolL t3,23 Diagnosis of embolism depends on the demonstration of a sudden ocVOLUME
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the Common sources are (1) atria1 thrombus occurring in a patient with atria1 fibrillation, (2) mural thrombus over a recent myocardial infarction, which occasionally may occur without symptoms except for the embolus, and (3) mitral stenosis even with regular sinus rhythm. More unusual causes are thrombosed pulmonary veins, paradoxic embolism, thrombus in a left ventricular aneurysm, thrombosis on an atheromatous plaque and myxoma of the left atrium. Diffuse arterial disease, such as periarteritis nodosa or disseminated lupus erythematosus, may be confused with multiple emboli and can cause confusion particularly if constitutional manifestations are also present.13
demonstration
case,67 along
with
of a source for embolism.
Three situations involving emboli seem to demand specialconsideration: (1) should reports
If an embolus is removed surgically it always be sectioned. There are many of myxoma diagnosed in this way17’46’61 ,68,69 The gross appearance of the embolus in some of these cases has suggested the diagnosis. (2) Emboli occurring in patients before the age of 20 are very rare, apart from bacterial endocarditis*gv70*71 Thus, angiography to exclude left atria1 myxoma should be performed in all cases of embolism occurring before the age of 20. (3) Emboli occurring in patients with mitral stenosis and sinus rhythm are not unusual. It has been said that this condition should suggest myxoma. However, about one quarter of cases of embolism with mitral stenosis occur with sinus rhythm.72 If we assume that 10 per cent of patients with mitral obstruction will have emboli,73 and that one myxoma will occur with each 200 patients with mitral stenosis requiring operation3 [a figure that is too high (Table II)], one can calculate that mitral stenosis with regular rhythm is at least 12 times as common a source for emboli as myxoma. This is not likely to be a useful indication for angiocardiography, because the yield of rnyxomas will be too small, unless some other feature of the case suggests myxoma. Unfortunately, there are patients who die of cerebral infarction from embolism arising from myxoma without any obstructive signs or symptoms, 73*74and if this is their initial embolus it will be completely unsuspected and undiagnosed.
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372 TABLE
II
Causes of Obstruction to Left Atria1 Outflow Noted at Operation at the Toronto General Hospital January 1950 to February 1967
would be considered. Fortunately, from a review of the reported cases, constitutional manifestations occurring for a long period as a sole manifestation are unusual.
No. of Cases RESULTS
Mitral stenosis Myxoma of left atrium* Cor triatriatum (mild) Supravalvular
mitral stenosis
Ball valve thrombus
1743 4 1 (Angiography, not operated on) 1 (Probable,
0
relieved by
closed operation)
* During this period of time, two additional unsuspected myxomas of the left atrium were found at postmortem examination in patients who had died of emboli; there were no destructive or constitutional symptoms.
Myxoma of Left Atrium Presenting with Obstructive Symbtoms and Signs: These patients are usually confused with those having mitral Suspicion should be aroused: (1) stenosis. if the progression is inexorably rapid; (2) if of sympsyncope occurs ; (3) if the progression toms is irregular, i.e., if there are unusual remissions of dyspnea, particularly if the remission occurs after an embolu?O; (4) if there is an unusual variation in symptoms with posture, e.g., faintness on stooping, dyspnea relieved by lying down; (5) if the murmurs are atypical or hard to hear; (6) if the physical signs or dye curves are unlike mitral regurgitation and if at catheterization large v waves in the wedge or left atria1 pressure tracing suggest mitral regurgitation, a combination suggesting myxoma.“6*51 Signs and symptoms of left atria1 outflow obstruction can be caused by mitral stenosis, myxoma of the left atrium, car triatriatum,75-81 supravalvular mitral stenosis,82 or perhaps by ball thrombus. By far the commonest cause is mitral stenosis (Table II). It is a tribute to surgical skill that 3 of the 4 patients with left atria1 myxoma referred to in Table II are still alive and well8 although only 1 &i was diagnosed before operation. The other 3 cases were encountered at closed operation for mitral stenosis. Diagnosis of Left Atria1 Myxoma in Patients Presenting with Constitutional Signs: These cases may be confused with bacterial endocarditis, active rheumatic fever, or some other collagen disease, such as disseminated lupus erythematosus, hidden malignant lesion, a lymphoma, or some obscure infection. Splenomegaly rarely if ever occurs with nlyxoma.2 Without obstructive or embolic manifestations it is unlikely that the diagnosis
OF SIJRGERY THE
LEFT
IN MYXOMA
OF
ATRIUM
A recent review’ of 58 attempted excisions of atria1 myxoma (both right and left), reported since 1959, demonstrated an over-all mortality of 26 per cent. The immediate results of surgical excision have been good, but information about late results is scanty. Three patients successfully operated on at the Toronto General Hospital* without resection of the adjacent atria1 wall have remained well and have normal left atria1 angiograms 5 to 10 years after removal of the tumor. Scannell in 196484 reported that a patient from whom he had removed a left atria1 myxoma in 195685 was still well. These are the only long-term follow-up observations noted. However, it is probably significant that there are no reports of recurrence after operation, although the first operations were performed more than 10 years ago. 5 z6 RIGHT
ATRIAL
MYXOMA
Two excellent papers24*26 on right atria1 myxoma appeared within a year of each other, analyzing the clinical picture in the reported cases of right atria1 myxoma and adding cases of their own. I can do no better than to quote extensively from these authors. Right heart failure invariably developed in these patients and was usually rapidly progressive and unresponsive to treatment. It was typically evidenced by distended neck veins, a big liver, ascites and edema, without clinical or radiologic signs of left heart failure. The patients were not orthopneic. Twenty-two of 25 patients (Table I) had either murmurs or friction rubs. About onethird had dizziness and syncope at times related to change in body position. About one-fifth had fever and sweats, but with negative blood cultures. Pulmonary emboli were rare. At first the patients were often considered to have tricuspid stenosis, constrictive pericarditis, nonspecific pericarditis, myocarditis, Ebstein’s malformation, carcinoid tumor, or superior vena caval obstruction. The electrocardiogram often showed large peaked P waves, low voltage, evidence of right bundle branch block or right THE
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Profile of Atria1 Myxoma ventricular hypertrophy and, occasionally, an abnormal T wa\-e. X-ray films showed calcification in 2 cases and usually right atria1 and right ventricular enlargement, with absence of vascular engorgement of the lungs despite advanced right heart failure. Unless there was a right to left shunt at atria1 level, there was a diastolic gradient across the tricuspid valve and right atria1 hypertension. The right atria1 pressure tracings in Morrisey’s 2 cases26 were indistinguishable from those seen in proved tricuspid stenosis. In all 12 of the patients submitted to angiocardiography the characteristic filling defect was demonstrated in the right In 1 the catheter was seen to be deatrium. flected by the tumor as the catheter passed through the right atrium. The lesson seems to be that tricuspid stenosis as an isolated lesion is probably as rare as myxoma. Ebstein’s malformation, too, is at times confused with myxoma but can be distinguished by angiocardiography. The use of an electrode catheter is said to be helpful, but not infallible.86 It seems reasonable to obtain angiocardiograms for patients in whom these rare diseases are suspected to exclude right atria1 myxoma. No long-term postoperative follow-up observations are available for patients with right atria1 myxoma. SUMMARY
AND
CONCLUSIONS
From a review of the recent literature on intracavitary myxomas of the heart the following conclusions seem justified : Intracavitary myxoma is a rare, benign tumor that is usually rapidly fatal if not recogIt can be abolished by surgical means nized. and has not been observed to recur, even without resection of the underlying atria1 wall. It can be visualized and easily recognized by appropriate selective angiocardiograms. The appropriate angiocardiogram should be obtained if the history, physical findings, or special investigations suggest the diagnosis. Atria1 myxomas cause embolic, obstructive and constitutional effects that include weight loss, fever, as well as biochemical and hematologic changes. Left atria1 myxoma, accounting for 75 per cent of the tumors, causes systemic emboli, mimics mitral obstruction and may be accompanied by constitutional effects. This combination may be confused with an infection. If one is dissatisfied with the nature of an infecVOLUME
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tion in a patient considered to have mitral disease, one should consider myxoma. Any surgically removed embolus should be sectioned, since unsuspected myxoma may be recognized in this way. Emboli occurring in patients before the age of 20 without bacterial endocarditis are so rare that this circumstance should lead to the suspicion of myxoma. Mitral valve disease is from 200 to 400 times as common a cause of left atria1 obstruction as myxoma. However, myxoma should be considered as a possible cause if: (1) progression of dyspnea is unusually rapid; (2) if syncope occurs; (3) if there are unusual remissions of dyspnea, particularly if the remission follows an embolus ; (4) if the murmurs are atypical or hard to hear; or (5) if there are unusual variations in symptoms with posture, e.g., faintness on stooping or dyspnea relieved by lying down. Right atria1 myxoma leads to failure of the right side of the heart that is usually rapidly progressive and unresponsive to treatment. Only 12 per cent of patients have no murmurs or rubs. Sounds resembling pericardial friction are heard in 20 per cent of patients and are possibly caused by tumor movement within the heart. Right atria1 myxoma may be confused with isolated tricuspid stenosis, Ebstein’s malformation, constrictive pericarditis, obscure myocardial disease and active rheumatic pericarditis. It seems reasonable to obtain angiograms showing the right atrium in patients suspected of having these rather rare diseases to exclude right atria1 myxoma. REFERENCES 1. NEWMAN, H. A., CORDELL, A. R. and PRICHARD, R. W. Intracardiac myxomas: Literature review and report of six cases, one successfully treated. Am. Surgeon, 32: 219, 1966. 2. GOODWIN, J. F. Diagnosis of left atria1 myxoma Lancet, 1: 464, 1963. 3. ALDRIDGE, H.E.and GREENWOOD, W.F. Myxoma of the left atrium. Bit. Heart J., 22: 189, 1960. 4. GOLDBERG, H. P., GLENN, F., DOTTER, C. T. and STEINBERG, I. Myxoma of left atrium: Diagnosis made during life with operative and postmortem findings. Circulation, 6: 762, 1952. 5. CRAFOORD, C. Panel discussion on late results of mitral commisurotomy. In: Henry Ford Hospital, Detroit, International Symposium on Cardiovascular Surgery: Studies in Physiology, diagnosis and Techniques, p. 202. Edited by LAMB, C. R. Philadelphia, 1955. W. B. Saunders. 6. BIGELOW, W. G., DOLAN, F. G. and CAMPBELL, F. W. The effect of hypothermia on the risk of surgery. In: Proceedings of the 16th Congress Internationale de Chirugie at Copenhagen, 1955,
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8.
9. 10. 11. 12.
13.
14.
15. 16. 17.
18. 19. 20. 21. 22.
23. 24.
25.
26.
27.
28. 29.
Greenwood p. 1. Brussels, 1955. Imprimerie Medicale et Scientifique (Sot. An.). KAY, E. B., RODRIGUEZ, P., HOGHIGHI, D., SUZUKI, A. and ZIMMERMAN, H. A. Mitral stenosis Comparative analysis of postoperative results following the closed and open operative approach. Am. J. Cardiol., 14: 139, 1964. FIROR, W. B., ALDRIDGE, H. E. and BIGELOW, W. G. .4 follow-up study of three patients after removal of left atria1 myxoma five to ten years previously. J. Thoracic & Cardiovas. Surg., 51: 515, 1966. FATTI, L. and REID, F. P. Excision of atria1 myxoma. Brit. M. J., 2: 531, 1958. Boss, J. H. and BECHAR, M. Myxoma of the heart. Am. J. Cardiol., 3: 823, 1959. BELLE, M. S. Right atria1 myxoma. Circulation, 19: 910, 1959. DESHMUKH, M., NICHOLS, H. T. and GOLDBERG, H. Myxoma of the left atrium simulating restenosis of the mitral valve. Am. Heart J., 58: 623, 1959. MACGREGOR, C. A. and CULLEN, R. A. The syndrome of fever, anaemia and high sedimentation rate with an atria1 myxoma. Brit. M. J., 2: 991, 1959. ASHMAN, H., ZAROFF, L. I. and BARONOFSKY, I. Right atria1 myxoma. Diagnosis during life. Successful surgical removal. Am. J. Med., 28: 487, 1960. BARLOW, J. B. Myxoma of left atrium. South African M. J., 34: 866, 1960. MARKOVITZ, M. and JOSEPH, S. R. Left atria1 myxoma. Arizona Med., 18: I, 1961. ZUIDEMA, G. D., BURKE, J. F., VILLEGAS, A. H. and SCANNELL, J. G. Surgery of left atria1 myxoma. New England J.‘Med., 264: 1016, 1961. BROADHURST, P. G. Report of a case of myxoma of the left atrium. M. J. Australia, 2: 789, 1961. CHAMOVITZ, D. L. and CARLSON, K. E. Myxoma of the left atrium. J.A.M.A., 179: 79, 1962. BLOODWORTH, J. M. B., JR. and SIJKARAI, M. Myxomaof the heart. Ohio M. J., 57: 161,196l. GOODWIN, J. F. et al. Clinical features of left atria1 myxoma. Thorax, 17: 91, 1962. PAHDI, R. K., KELLY, H. G. and LYNN, R. B. Intraatrial myxoma. Canad. J. Surg., 2: 414, 1959. CAMPEAU and DAVID, P. Myxoma of the heart. Canad. M. A. J., 82: 586, 1960. SANNERSTEDT, R. et al. Right atria1 myxoma-report of a case and review of the literature. Am. Heart J., 64: 243, 1962. BARNARD, C. N., SWANEPOEL, A., MCKENZIE, M. B. and PHILLIPS, W. L. Left atria1 myxoma. Report of a case treated successfully using extracorporeal circulation. Brit. J. Surg., 48: 73, 1960. MORRISEY, J. F., CAMPETI, F. L., MAHONEY, E. B. and Yu, P. N. Right atria1 myxoma. Report of two cases and review of the literature. Am. Heart J., 66: 4, 1963. HAIR, T. E., JR., ORGAIN, E. S., SEALY, W. C. and MCINTOSH, H. D. Myxoma of the left atrium. Observations on two cases, with successful removal and review of diagnostic methods. Am. J. Med., 32: 560, 1962. PRICHARD, R. W. Tumors of the heart. Arch. Path., 51: 98, 1951. SAKAKIBARA, S. et al. Myxoma of the right ven-
30.
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34. 35. 36.
37.
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39.
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44.
45.
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47. 48.
49.
tricle of the heart. Report of a case with successful removal and review of the literature. .4m. Heart J., 69: 382, 1965. MACRAE, F. R. and GALEA, M. Myxoma of the right ventricle of the heart. Canad. M. A. .J.: 85 : 435, 1961. CRUMMY, A. B. and HIPONA, F. j\. The radiographic aspects of right ventricular myxoma. Brit. J. Radial., 37: 468, 1964. FAYEN, .4. W. and BAGLIO, C. M. Primary myxoma occurring in the left ventricle of the heart. Am. J. Clin. Path., 32: 552, 1959. YOUNG, R. D. and HUNTER, W. C. Left ventricular myxoma-primary myxoma of the left ventricle with embolic occlusion of abdominal aorta and renal arteries. Arch. Path., 43: 86, 1947. BJORK, V. 0. and BJORK, L. Left ventricular myxoma. Thorax, 20: 534, 1965. Cardiovascular Pathology, Vol. 2, HUDSON, R. E. p. 1575. London, 1965. Edward Arnold. PITT, A., CRILEY, J. M., PITT, B. and SCHAEFER, J. Left atria1 myxoma; hemodynamic and phonocardiographic consequences of sudden volume changes caused by tumor movement. Circulation, 34 (Suppl. III): 188, 1965. FRANKENFELD, R. H., WATERS, C. H. and STEINER, R. 0. Bilateral myxomas of the heart. Ann. Int. Med., 53: 827, 1960. KAUFMAN, G., RUTISHAUSER, W. and HEGGLIN, R. Heart sounds in atria1 tumors. Am. J. Cardiol., 8: 350, 1961. GUMMING, G. R. and FINKEL, K. Intracardiac myxoma involving right and left atrium in a young patient. J. Pediat., 58: 559, 1961. OLIVER, C. G., JR. and MISSEN, G. A. K. A heavily calcified right atria1 myxoma. Guy’s Hosp. Rep., 115: 37, 1966. WRIGHT, R. P., JR., MCCALL, H. M. and WENGER, N. K. Primary atria1 tumors. Evaluation of clinical findings in 10 cases and review of the literature. Am. J. Cardiol., 11: 790, 1963. SMELLIE, H. Myxoma of the left atrium. Proc. Roy. Sot. Med., 55: 226, 1962. CATT, K., DENBOROUGH, M. A., GRIGG, L. and SLOMAN, G. Myxoma of right atrium. Brit. Heart J., 24: 525, 1962. EMMANUEL, R. W. and LLOYD, W. E. Right atria1 myxoma mistaken for constrictive pericarditis. Brit. Heart J., 24: 796, 1962. HOLSWADE, G. R. and STEINBERG, I. Right atria1 myxoma complicated by a thrombus. J.A.M.A., 193: 126, 1965. WILLMAN, V. L., SYMBAS, P. N., MAMIYA, R. T., COOPER, T. and HANLON, C. R. Unusual aspects of intracavitary tumors of the heart. (Report of two cases.) Dis. Chest, 47: 669, 1965. TABER, R. E., DRAKE, E. H. and GALE, H. M. Cardiac myxomas. Dis. Chest, 47: 102, 1965. BARLOW, J., FULLER, D. and DENNY, M. A case of right atria1 myxoma with special reference to an unusual phonocardiographic finding. Brit. Heart J., 24: 120, 1962. COATES, E. O., JR. and DRAKE, E. H. Myxoma of the right atrium with variable right to left shunt. Clinical and physiological observations and report of a case with successful operative removal. New England J. Med., 259: 165, 1958. THE
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F., SOBORN, .J. .J., ROBSON, G. B., BRAINM. and HILTGREN, H. Left atrial myxoma: successful removal with the aid of extracorporeal circulation. Ann. Surg., 147: 320, 1958. ELLIS, F. H., JR., MANKIN, H. T. and BURCHELL, II. B. Myxoma of the atrium: successful surgical treatment in two cases. M. Clin. ;Vorth America, 42: 1087, 1958. ~h’kTHEY, J. et al. Trois cas de myxoma intracardiaquc operes. Mim. Acad. chir., 85: 425, 1359. COHEN, A. I., MCINTOSH, H. D. and ORGAIN, E. S. The mimetic nature of left atria1 myxomas. Am. J. Cardiol., 11: 802, 1963. HORLICK, L. and MERRIMAN, J. E. Atria1 myxoma. Canad. M. A. J., 77: 582, 1957. LEFCOE, N. M., BRIAN, F. G. and MANNING, G. W. An opening snap recorded in a case of tumor of left atrium. ;VPW England J. Med., 257: 178, 1957. WASSERMIL, M., WARKENTIN, D. L. and RAVIN, A. Myxoma of the left atrium-phonocardiographic study of three cases. Circulation, 25 : 50, 1952. LEVINSON, J. P. and KINCAID, 0. W. Myxoma of the right atrium associated with polycythemia. ,Vew England J. Med., 264: 1187, 1961. SKANSE, B., BARA, N. 0. and WESTFIELD, T. A. Atria1 myxoma with Raynaud’s phenomenon as the initial symptom. Acta med. scandinau., 164: 321, 1959. VUOPIO, P. and NIKKIL;~, E. A. Hemolytic anemia and thrombocytopenia in a case of left atria1 myxoma associated with mitral stenosis. Am. J. Cardial., 17: 585, 1966. GOODWIN, J. F., KAY, J. M. and HEATH, D. Clinical pathological conference. Am. Heart J., 70: 239, 1965. ROPER, C. L., CAMP, F. A. and KEMPSON, R. L. Atria1 myxoma associated with fibroadenomas of the breast. Missouri Med., 62: 113, 1965. FRIEDBERG, S. L., OGNIBENE, A. J. and DOTO, W. R. Left atria1 myxoma and fatal abacterial pneumonia. J. Lancet, 85: 328, 1965. LOURIA, D. B., BLUMENFELD, H. L., ELLIS, J. T., KILBOURNE, E. D. and ROGERS, D. E. Studies on influenza in the pandemic of 1957 to 1958. II. Pulmonary complications of influenza. J. Gin. Invest., 38: 213, 1959. CURREY, H. F. L., MATHEWS, J. A. and ROBINSON, J. Right atria1 myxoma mimicking a rheumatic disorder. Brit. M. J., 1: 547, 1967. &GAL, B. L. Introduction to symposium on Echocardiography. Am. J. Cardiol., 19: 1, 1967. DICK, H. J. and MULLIN, E. W. Myxoma of the heart complicated by bloodstream infection: Staphylococcus aureus and candida parapsilosis. New York J. Med., 56: 856, 1956.
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and \YOLSTEAD, P. M. I,rft atria1 IXs. Chest, 38: 429, 1960. EDWARDS, .i. T. and JOHNSON, \2;. A case of myxoma of the left atrium with peripheral arterial emboli. Brit. J. Surg., 46: 391, 1959. BEANLANDS, D. S., ROY, D. L., DOLAN, F. G. and SHANE, S. J. Myxoma of the left atrium. Canad. M. A. .J., 83: 715, 1969. REALE, A., COLELLA, C. and BRUNO, A. M. Mitral stenosis in childhood, clinical and therapeutic aspects. Am. Heart J., 66: 15, 1963. BROWN, K. W. G. and GREENWOOD, W. F. Unpublished observations. WOOD, P. Diseases of the Heart and Circulation, cd. 2, p. 525. London 1956. Eyre and Spottiswood. KRAPIN, D. Myxoma of left atrium showing signs of a cerebral lesion. New York J. Med., 63: 3136, 1963. Records of the Toronto General Hospital. History No. B.22354. BARRETT, N. R. and HICKIE, J. B. Cor triatriatum. Thorax, 12: 24, 1957. STRETTON, T. M. and FENTON, T. B. Stenosis of the left atria1 A-V canal. Brit. Heart J., 24: 237, 1962. BELCHER, J. R. and SOMMERVILLE, W. B. Cor triatriatum-stenosis of the common pulmonary veinsuccessful treatment of a case. Brit. h4. J., 1: 1280, 1959. SLADE, P. R., TUBBS, 0. S. and WELLS, R. G. Cor triatriatum-a case corrected by surgery. Brit. Heart J., 24: 233, 1962. LAM, C. R., ZIEGLER, R. F., DRAKE, E. I-I. and GREEN, E. Diagnosis and treatment of a type of triatrial heart. Circulation, 20: 723, 1959. VINEBERG, A. and GIALLORETTO, 0. Report of successful operation for stenosis of common pulmonary vein (car triatriatum). Canad. M. A. J., 74: 719, 1956. LEWIS, F. J., VARCO, R. L., TAUFIC, M. and NIAGI, S. -4. Direct vision repair of triatrial heart and of total anomalous pulmonary venous drainage. Surg., Gym. CT Obst., 102: 713, 1956. LYNCH, H. F. et al. Supravalvular mitral stenosis. Circulation, 25: 854, 1952. A~~DERSON, R. N., ALDRIDGE, H. E. and GREENWOOD, W. F. Left atria1 myxoma. Brit. Heart J., 23: 725, 1961. SCANNELL, J. G. Discussion in case records of the Massachusetts General Hospital. Avew England J. Med., 271: 787, 1964. SCANNELL, J. G., BREWSTER, W. R. and BLAND, E. F. Successful removal of a myxoma from the left atrium. New England J. Med., 254: 601, 1956. WATSON, H. Electrode catheters and the diagnosis of Ebstein’s anomaly of the tricuspid valve. Brit. Heart .I., 28: 161, 1966. DUGAN,
myxoma.
BRIDGE,
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FREDERICK GREENWOOD, Toronto,
M.D.*
Canada
view of the literature, to designate the wide spectrum of disease which these tumors can mimic; to try to determine how myxoma differs clinically from the diseases it mimics, and to decide under what conditions one should suspect myxoma and obtain the appropriate angiogram.
YXOMA, a benign intracavitary tumor of the heart, is rare. By 1965 about 350 cases had been reported.’ It is important because it can be abolished by surgical therapy and is usually rapidly fatal if unrecognized and untreated. Diagnosis by angiocardiography seems to be quite accurate; in most of the cases in which myxoma was diagnosed before operation, it was demonstrated in this way. However, false positives2 and false negatives3 have been observed. The lesion must be suspected before the appropriate angiogram is made. The clinical diagnosis was first made by angiography in 1951 ,4 and the first successful surgical excisions were performed in 1955.5,6 A wider use of angiocardiography in the routine investigation of valve lesions before surgery can be expected to increase the number of myxomas found preoperatively; the practice of using cardiopulmonary bypass for all mitral commissurotomies’ or having it available promptly to surgeons performing closed mitral commissurotomies should increase the number of successful resections among those cases found unexpectedly at 0peration.s One important factor in attaining recognition and cure will be the painfully acquired habit of doubting the obvious, a trait of physicians who practice under conditions in which successes and failures are regularly exposed by colleagues in surgery or pathology. No one person can hope to see a sufficient number of these tumors to appreciate from his own experience the many ways in which they manifest themselves. In the past 10 years many authors,g-27 after reporting a few cases of their own, reviewing a group of the reported cases and, in some instances, using their imagination have suggested methods for suspecting the presence of myxoma. The object of this study is, by a critical re-
M
CONSIDERATIONS COMMON TO ALL INTRACAVITARY MYXOMAS The Anatomy of the Lesion: Three quarters of these tumors arise in the left atrium, and nearly all the rest in the right.2s A few, some of which have been successfully removed surgically, have occurred in the ventricles.2g-34 Characteristically, atria1 myxomas arise in or near the fossa ovalis and are pedunculated.3j The pedicle may be short, allowing little movement, or it may be long, allowing the tumor to pass back and forth from atrium to ventricle during the cardiac cycle.2v24*36 Sometimes the tumor has a distinct mark made by the valve ring on its surface, dividing it into distinct atria1 and ventricular segments, thus indicating residence in the ring. It may be solid and spherical or lobulated and have villous projections. These tumors are almost always solitary, but a patient with one large and three small pedunculated tumors in the right atrium and a pedunculated polypoid tumor in the left atrium has been reported by Frankenfeld et a1.37 Kaufman et a1.3s have reported successful surgical removal at one operation of right and left atria1 myxomas which had given rise to both pulmonary and systemic emboli. An 11 year old boy, reported on by Gumming and Finkel,“g had both pulmonary and systemic emboli from a myxoma of the left atrium which extended through the foramen ovale to form a mass 3.5 by 2 by 1 cm. in the right atrium. Gross calcijication is rarely present in myxomas. It has been visualized fluoroscopically in 2
* From the Department of Medicine, University of Toronto, and the Cardiovascular Unit, Toronto General Hospital, Ontario, Canada. Address for reprints: William F. Greenwood, M.D., Cardiovascular Unit, Toronto General Hospital, Toronto 2. Ontario, Canada. VOLUME
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cases of right atria140a4i and 1 of left atria1 myxonla.4? A myxoma from the right atrium showed hemorrhages and some calcification after remova1.43 Relation Between the Anatomy of the Lesion and the Signs and Symptoms: As first pointed out by Goodwin,? myxomas show themselves clinically in three ways, (1) by embolization, (2) by obstruction to the flow of blood and (3) by constitutional effects; that is, by producing symptoms and signs of a constitutional nature as well as changes in the blood which can be detected by hematologic or biochemical examination. EMBOLIZATION Emboli arising in patients with myxoma can consist of tumor fragments or thrombus from the surface of the tumor. Occasionally nearly the whole tumor has been observed to break off, thus obstructing the bifurcation of the aorta. Tumors in either the left or right side of the heart may- obstruct blood flow and lead to congestive heart failure; therefore, venous thrombosis and pulmonary embolism, which commonly complicate failure, would be expected to occur in patients with myxoma of either Pulmonary arterial obstruction ocatrium. curred in 13 of 45 cases of left atria1 myxoma reported by Goodwim2 but in only 243,44 of 282df45-8 cases of right atria1 myxoma was pulmonary embolism noted clinically. It is an odd paradox that pulmonary arterial obstruction seems to be commoner in left atria1 myxoma than in right. In right atria1 myxoma arterial unsaturation presumably due to a right to left shunt occasionally occurs11,46,4g (i.e., in 3 of the 28 cases previously referred to). Although one might expect paradoxic embolism occasionally with right atria1 myxoma, to my knowledge it has not so far been reported. Systemic embolism from myxoma has so far been seen in cases of myxoma of the left atrium, in which it occurred in approximately 40 per cent of patients,2~3~23 and of the left ventricle, in which it occurred in 4 of the 5 reported cases.32-34 THE RESULTS OF OBSTRUCTION TO BLOOD FLOW Small tumors, unless they lead to emboli, are usually asymptomatic. As they enlarge they obstruct, interfering with the transfer of blood from pulmonary or systemic veins through the atrium to the ventricle and leading to the signs and symptoms of congestive heart failure.
The tumor may obstruct the atrioventricular valve, or it may nearly fill the atrium, which usually does not become much enlarged probably because it is not diseased. It is interesting that x-ray evidence of left atria1 enlargement present before operation has disappeared after removal of the tumor.* The obstruction is characteristically inexorably progressive, thus giving rise to the statement that these tumors are pathologically benign but clinically malignant.2g Less commonly, a tumor on a pedicle that allows movement may cause intermittent obstruction leading to syncope or sudden death. This condition occurs in less than a quarter of the cases2 t3,23 More rarely,13J*~50 a remarkable remission from dyspnea or established congestive failure presumably due to intermittent obstruction, may occur in the course of the disease. In Gerbode’s cases0 this relief, which lasted 20 months, followed the occurrence of peripheral emboli from which the patient recovered. Murmurs: Obstruction usually leads to the diastolic murmur characteristic of mitral or tricuspid obstruction, but if valve closure is prevented by the tumor a systolic murmur due to regurgitation may be produced. Variation in murmurs with time and with change in position has been noted and stressed by some as an important clue to the possible presence of myxoma . It is well known that the intensity of the murmur of mitral stenosis characteristically is louder when the patient is lying on his left side, and that its intensity increases with activity or when the patient comes out of congestive failure. To arouse suspicion, therefore, variation in murmurs with time or position must be unlike the variation found in mitral disease. This variability is not often mentioned in the case reports reviewed, although it often appears in the list of possible clues to the presence of a myxoma. Obviously the fallibility of the human memory, even aided by notes, would limit the usefulness of variation in murmurs as a clue even if it were to occur with any frequency. The situation reminds one of the variable murmurs of bacterial endocarditis, which are so often talked about and so seldom seen. Friction Rub: In one reported case of myxoma of the right atrium, a loud systolic crunching noise at the lower end of the sternum with an elevated venous pressure and constitutional manifestations led to the diagnosis of tuberTHE
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clllosis pericarditis.44 In a second patient with a right atria1 myxoma that was successfully removed under hypothermia, a loud “pleuropericardial friction rub” persisted throughout his illness.4” In Frankenfeld’s3’ patient with bilateral myxomas a to-and-fro crunching rub at the left sternal border was heard. In 2 other patients with right atria1 myxoma pericardial friction rubs were noted.51s52 These odd noises may have resulted from the tumor rubbing on the endocardial surface of the heart during the cardiac cycle. I have seen a report of a similar noise in only 1 case of left atria1 myxoma.53 Perhaps because of the posterior position of the left atrium a rub caused by a tumor is seldom heard. Opening snaps have been heard and recorded in patients with left atria1 myxoma.36t54-6 Wassermil et a1.56 have noted in phonocardiograms of 3 patients with left atria1 myxoma an accentuated and a delayed first sound (QS interval) and accentuated pulmonary valve clos-’ ure. They have noted presystolic mitral murmurs in 2 of their 3 patients and conclude that the findings are the same as in mitral stenosis. However, mitral murmurs were absent in 1 case, intermittent or faint in 1 and apparently fairly obvious in only 1. Pitt et a1.36 have recorded simultaneously phonocardiograms, left ventricular pressure tracings and cineangiograms in 2 patients with left atria1 myxoma. With ventricular contraction the tumor entered the left atrium, and at this time large left atria1 v waves occurred in the absence of mitral regurgitation, and a notch occurred on the rising record of left ventricular pressure. These events corresponded with a loud first heart sound. An opening snap occurred after the mitral valve opened and was synchronous with checking the excursion of the tumor once it was in the left ventricle. Thus, these sounds, although clinically indistinguishable from those produced by mitral stenosis, appear to be due to tumor movement in these patients and may not originate at the mitral valve. Goodwin2 in his review of 45 cases observed by members of the British Cardiac Society states that in the typical patient the murmurs were atypical or hard to hear. This is probably as near as one can come to a helpful statement about the physical findings in left atria1 myxoma. The ausculatory jkdings in 25 reported cases of right atria1 myxoma24~26~43J4,48 are shown in Table I. It is apparent that 80 per cent of VOLUME
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369 TABLE
The
I
Findings on Auscultation in 25 Reported of Right Atria1 Myxoma24~s6~437bP.1Y
Casey
Diastolic rn~rrn~l~ only Systolic and diastolic rnwrnw~ Murmurs and a friction rllb Systolic mwmur only Friction rub only No mumnm or rllbs Total caged analyzed
patients had murmurs, 20 per cent had pericardial friction rubs and only 12 per cent had no murmurs or rubs. CONSTITUTIONAL MYXOMA
EFFECTS OF THE
OF
HEART
From a review of individual published cases, it is impossible to form any reliable opinion about the incidence of inconspicuous constitutional signs and symptoms. However, Goodwin2 sent a questionnaire to the members of the British Cardiac Society about their cases of left atria1 myxoma. The answers he received enabled him to determine that 40 of the 45 patients (89 per cent) represented by this survey had one of the following five constitutional manifestations : fever (53 per cent), raised sedimentation rate (69 per cent), weight loss (36 per cent), anemia (44 per cent) and abnormal serum proteins (48 per cent). He also showed that these manifestations occurred much more frequently in patients with myxoma than in those who had uncomplicated mitral stenosis. However, mitral stenosis is often complicated by pulmonary infection, pulmonary infarction, active rheumatic fever, severe chronic passive congestion of liver, bland thrombosis in leg veins and bacterial endocarditis. It may also exist with other diseases that can cause COIItitutional effects. In searching for the cause of constitutional manifestations in a patient with heart disease it seems apparent that one must add myxoma to the list of possibilities. Fever,22 ,43 elevation of sedimentation rate,22 .24,43,44 elevation of gamma globulin57 and weight loss 48 have been reported in association with myxomas of the right atrium and right ventricle. However, right atria1 myxomas, unlike those on the left side, tend to have a high hemoglobin,24 which is sometimes46 but not always associated with arterial hypoxia at rest. The arterial hypoxia occasionally observed in
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right atria1 In)-xolrla may be due to a shunt through a dilated foramen ovale,4fi or through a coexisting atria1 septal defect.4” Clubbing has occurred in both right46 and left-sided rnyxomas,2 Al in the former instance with arterial unsaturation. Raynaud’s phenomenon has occurred as the initial symptom in a 15 year old gir1.58 There are isolated reports of other constitutional and hematologic effects of myxoma. Vuopia and NikkilZ 5g have reported a case of mitral stenosis with left atria1 myxoma and hemolytic anemia probably due to mechanical destruction of blood by turbulence. This patient had a hemoglobin of 6.4 gm./lOO ml. with 16 per cent reticulocytes, a white blond count up to 32,000 per cu. mm. and thrombocytopenia (platelets 2,600 to 34,000 per cu. mm.). Bizarre poikilocytes were observed in the smear. The myxoma was found at postmortem examination. Willman et a1.46 have described a woman with striking clubbing of the fingers, heart failure, arterial unsaturation (88 per cent decreasing to 66 per cent after 30 minutes supine), purpuric spots and a platelet count of 30,000 per cu. mm. The platelets did not increase after administration of cortisone but within three days after removal of a right atria1 myxoma the count rose to 230,000 and the cyanosis disappeared. Thus it appears that myxorna can cause increased destruction of both red blood cells and platelets. This fact suggests that minor degrees of hemolysis and an increased platelet turnover might be present in many other cases if one looked for it. On the other hand, in the case of Levinson and Kincaid57 the hematocrit was 54 per cent and the platelet count 1,386 per cu. mm. before removal of a right atria1 myxoma. The C-reactive protein has been elevated (2+ to 4f in 3 cases) .37 J* s4* White blood counts of over 18,000 per cu. mm. have occurred.18JgJ2~30~~0 It should be worthwhile examining the blood for elevations of transaminases if multiple small emboli to muscles occur and account for some of the constitutional manifestations as suggested by Goodwin.2 Elevation of serum glutamic oxalacetic transaminase to 188 units has been reported in a case of left atria1 myxoma.60 For the same reason microscopic hematuria should be looked for although it has not been reported. Roper et al.‘jl have reported 2 cases of left atria1 myxoma associated with fibroadenoma In each case the secof the breast in women.
tions of the breast showed myxomatous stronta in the fibroadenomas. They suggest that there may be rnyxomatous change in 111ore than one: organ system. A 23 year old male patient,6” admitted to ,i U. S. Army Hospital in Nuremberg, had a fulminating pneumonia and died within 30 hours of the onset of illness. At postmortem examination a left atria1 myxoma 3 by 2 by 2 cm. Intimal atheroma and hemosiderowas found. sis of the lungs suggested pre-existing pulmonary hypertension. They compared the rapidly deteriorating condition with that of patients with rheumatic heart disease observed by Louria et a1.63 during an influenza pandemic. However, no other suggestion has been made that patients with myxoma have an increased susceptibility to infection. The factors causing constitutional disturHemorrhage and bances are not entirely clear. degeneration within the turnor13 or multiple small emboli to muscles2 have been suggested. An immune response to fragments of tumor released into the circulation has been invoked as a possible cause of the increase in gamma globulins.10 Currey et al. 64 have reported immunologic studies, before and after operation, in a patient with a right atria1 myxoma and conspicuous constitutional manifestations that Antibodies cleared after removal of the tumor. to myxoma were not demonstrated, but antibodies to fresh human heart muscle were present before operation, the titer dropping from 1 : 120 to 1 :40 four months after operation. The) have previously demonstrated these antibodies in a high percentage of patients with postcardiotomy and postmyocardial infarction syndromes. They suggest, “It is possible that an intracardiac myxoma may initiate and maintain an autoimmune state analogous to that seen after cardiotomy or myocardial infarction.” DIAGNOSIS MYXOMAS
OF LEFT AND RIGHT BY ANGIOCARDIOGRAPHY
ATRIAL
Left Atrial Myxoma: With modern equipment and contrast media, selective injection of the radiopaque dye into the pulmonary artery with a Gidlund compressed-air syringe and the use of cineangiography with 30 or more frames a second, the pictures of the left atrium obtained now are so good that it seems unlikely that false positives or negatives would now plague us. In 1958 a patient with a myxoma that was not detected by angiography was described.51 False positives have also been deTHE
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scribed.2a3 In 1 of these patients the error was
elusion of a systemic artery or a series of such
ascribed to blood from the pulmonary veins diluting the contrast medium.2 In the second3 the injection was made into the left atrium, and it swirled around, thus presenting an appearance that caused some concern about the presence of a filling defect. At operation with a pump standby the patient had mitral stenosis. Clot and myxoma can theoretically be confused, but to my knowledge have not been. The movement of a myxoma is unmistakable, if it is observed angiographically.2~24~36 Right Atria1 Myxoma: In this case, the injection is made into one of the venae cavae or the right atrium. The former is probably preferable. A technically satisfactory angiogram should now be possible, and for the reasons cited above, it seems unlikely that errors in diagnosis would occur with modern technics. The Use of Ultra Sound in the Diagnosis of Atria1 Myxoma: Sega1,‘j5 states that “atria1 thrombi or myxoma have occasionally been suspected in the preoperative evaluation of patients using ultrasonic technics. However, much more experience is necessary to determine the accuracy of ultra sound for detecting these conditions.”
occlusions,
DIFFERENTIAL DIAGNOSIS OF LEFT ATRIAL MYXOMA
In Patients Presenting with Obstruction, Emboli and Constitutional Manifestations: In patients presenting with a combination of these three types of symptoms and signs one should consider the possibility of left atria1 myxoma, as well as mitral disease complicated by bacterial endocarditis, or some other infection, including active rheumatic disease. Consistently negative blood cultures do not exclude bacterial endocarditis, but when combined with a lack of response to antibiotics one should probably obtain an angiocardiogram to exclude myxoma. The presence of positive blood cultures is most unusual in myxoma but has been reported once.6F A history of rheumatic fever or the presence of aortic murmurs makes myxoma unlikely but does not exclude it. If one is dissatisfied with the nature of a suspected infection in a patient considered to have mitral stenosis, one should consider myxoma. In Patients with Emboli Alone: About 45 per cent of left atria1 myxomas give rise to systemic embolL t3,23 Diagnosis of embolism depends on the demonstration of a sudden ocVOLUME
21, MARCH
1968
as in Dugan’s
the Common sources are (1) atria1 thrombus occurring in a patient with atria1 fibrillation, (2) mural thrombus over a recent myocardial infarction, which occasionally may occur without symptoms except for the embolus, and (3) mitral stenosis even with regular sinus rhythm. More unusual causes are thrombosed pulmonary veins, paradoxic embolism, thrombus in a left ventricular aneurysm, thrombosis on an atheromatous plaque and myxoma of the left atrium. Diffuse arterial disease, such as periarteritis nodosa or disseminated lupus erythematosus, may be confused with multiple emboli and can cause confusion particularly if constitutional manifestations are also present.13
demonstration
case,67 along
with
of a source for embolism.
Three situations involving emboli seem to demand specialconsideration: (1) should reports
If an embolus is removed surgically it always be sectioned. There are many of myxoma diagnosed in this way17’46’61 ,68,69 The gross appearance of the embolus in some of these cases has suggested the diagnosis. (2) Emboli occurring in patients before the age of 20 are very rare, apart from bacterial endocarditis*gv70*71 Thus, angiography to exclude left atria1 myxoma should be performed in all cases of embolism occurring before the age of 20. (3) Emboli occurring in patients with mitral stenosis and sinus rhythm are not unusual. It has been said that this condition should suggest myxoma. However, about one quarter of cases of embolism with mitral stenosis occur with sinus rhythm.72 If we assume that 10 per cent of patients with mitral obstruction will have emboli,73 and that one myxoma will occur with each 200 patients with mitral stenosis requiring operation3 [a figure that is too high (Table II)], one can calculate that mitral stenosis with regular rhythm is at least 12 times as common a source for emboli as myxoma. This is not likely to be a useful indication for angiocardiography, because the yield of rnyxomas will be too small, unless some other feature of the case suggests myxoma. Unfortunately, there are patients who die of cerebral infarction from embolism arising from myxoma without any obstructive signs or symptoms, 73*74and if this is their initial embolus it will be completely unsuspected and undiagnosed.
Greenwood
372 TABLE
II
Causes of Obstruction to Left Atria1 Outflow Noted at Operation at the Toronto General Hospital January 1950 to February 1967
would be considered. Fortunately, from a review of the reported cases, constitutional manifestations occurring for a long period as a sole manifestation are unusual.
No. of Cases RESULTS
Mitral stenosis Myxoma of left atrium* Cor triatriatum (mild) Supravalvular
mitral stenosis
Ball valve thrombus
1743 4 1 (Angiography, not operated on) 1 (Probable,
0
relieved by
closed operation)
* During this period of time, two additional unsuspected myxomas of the left atrium were found at postmortem examination in patients who had died of emboli; there were no destructive or constitutional symptoms.
Myxoma of Left Atrium Presenting with Obstructive Symbtoms and Signs: These patients are usually confused with those having mitral Suspicion should be aroused: (1) stenosis. if the progression is inexorably rapid; (2) if of sympsyncope occurs ; (3) if the progression toms is irregular, i.e., if there are unusual remissions of dyspnea, particularly if the remission occurs after an embolu?O; (4) if there is an unusual variation in symptoms with posture, e.g., faintness on stooping, dyspnea relieved by lying down; (5) if the murmurs are atypical or hard to hear; (6) if the physical signs or dye curves are unlike mitral regurgitation and if at catheterization large v waves in the wedge or left atria1 pressure tracing suggest mitral regurgitation, a combination suggesting myxoma.“6*51 Signs and symptoms of left atria1 outflow obstruction can be caused by mitral stenosis, myxoma of the left atrium, car triatriatum,75-81 supravalvular mitral stenosis,82 or perhaps by ball thrombus. By far the commonest cause is mitral stenosis (Table II). It is a tribute to surgical skill that 3 of the 4 patients with left atria1 myxoma referred to in Table II are still alive and well8 although only 1 &i was diagnosed before operation. The other 3 cases were encountered at closed operation for mitral stenosis. Diagnosis of Left Atria1 Myxoma in Patients Presenting with Constitutional Signs: These cases may be confused with bacterial endocarditis, active rheumatic fever, or some other collagen disease, such as disseminated lupus erythematosus, hidden malignant lesion, a lymphoma, or some obscure infection. Splenomegaly rarely if ever occurs with nlyxoma.2 Without obstructive or embolic manifestations it is unlikely that the diagnosis
OF SIJRGERY THE
LEFT
IN MYXOMA
OF
ATRIUM
A recent review’ of 58 attempted excisions of atria1 myxoma (both right and left), reported since 1959, demonstrated an over-all mortality of 26 per cent. The immediate results of surgical excision have been good, but information about late results is scanty. Three patients successfully operated on at the Toronto General Hospital* without resection of the adjacent atria1 wall have remained well and have normal left atria1 angiograms 5 to 10 years after removal of the tumor. Scannell in 196484 reported that a patient from whom he had removed a left atria1 myxoma in 195685 was still well. These are the only long-term follow-up observations noted. However, it is probably significant that there are no reports of recurrence after operation, although the first operations were performed more than 10 years ago. 5 z6 RIGHT
ATRIAL
MYXOMA
Two excellent papers24*26 on right atria1 myxoma appeared within a year of each other, analyzing the clinical picture in the reported cases of right atria1 myxoma and adding cases of their own. I can do no better than to quote extensively from these authors. Right heart failure invariably developed in these patients and was usually rapidly progressive and unresponsive to treatment. It was typically evidenced by distended neck veins, a big liver, ascites and edema, without clinical or radiologic signs of left heart failure. The patients were not orthopneic. Twenty-two of 25 patients (Table I) had either murmurs or friction rubs. About onethird had dizziness and syncope at times related to change in body position. About one-fifth had fever and sweats, but with negative blood cultures. Pulmonary emboli were rare. At first the patients were often considered to have tricuspid stenosis, constrictive pericarditis, nonspecific pericarditis, myocarditis, Ebstein’s malformation, carcinoid tumor, or superior vena caval obstruction. The electrocardiogram often showed large peaked P waves, low voltage, evidence of right bundle branch block or right THE
AMERICAN
JOURNAL
OF CARDIOLOGY
Profile of Atria1 Myxoma ventricular hypertrophy and, occasionally, an abnormal T wa\-e. X-ray films showed calcification in 2 cases and usually right atria1 and right ventricular enlargement, with absence of vascular engorgement of the lungs despite advanced right heart failure. Unless there was a right to left shunt at atria1 level, there was a diastolic gradient across the tricuspid valve and right atria1 hypertension. The right atria1 pressure tracings in Morrisey’s 2 cases26 were indistinguishable from those seen in proved tricuspid stenosis. In all 12 of the patients submitted to angiocardiography the characteristic filling defect was demonstrated in the right In 1 the catheter was seen to be deatrium. flected by the tumor as the catheter passed through the right atrium. The lesson seems to be that tricuspid stenosis as an isolated lesion is probably as rare as myxoma. Ebstein’s malformation, too, is at times confused with myxoma but can be distinguished by angiocardiography. The use of an electrode catheter is said to be helpful, but not infallible.86 It seems reasonable to obtain angiocardiograms for patients in whom these rare diseases are suspected to exclude right atria1 myxoma. No long-term postoperative follow-up observations are available for patients with right atria1 myxoma. SUMMARY
AND
CONCLUSIONS
From a review of the recent literature on intracavitary myxomas of the heart the following conclusions seem justified : Intracavitary myxoma is a rare, benign tumor that is usually rapidly fatal if not recogIt can be abolished by surgical means nized. and has not been observed to recur, even without resection of the underlying atria1 wall. It can be visualized and easily recognized by appropriate selective angiocardiograms. The appropriate angiocardiogram should be obtained if the history, physical findings, or special investigations suggest the diagnosis. Atria1 myxomas cause embolic, obstructive and constitutional effects that include weight loss, fever, as well as biochemical and hematologic changes. Left atria1 myxoma, accounting for 75 per cent of the tumors, causes systemic emboli, mimics mitral obstruction and may be accompanied by constitutional effects. This combination may be confused with an infection. If one is dissatisfied with the nature of an infecVOLUME
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1968
373
tion in a patient considered to have mitral disease, one should consider myxoma. Any surgically removed embolus should be sectioned, since unsuspected myxoma may be recognized in this way. Emboli occurring in patients before the age of 20 without bacterial endocarditis are so rare that this circumstance should lead to the suspicion of myxoma. Mitral valve disease is from 200 to 400 times as common a cause of left atria1 obstruction as myxoma. However, myxoma should be considered as a possible cause if: (1) progression of dyspnea is unusually rapid; (2) if syncope occurs; (3) if there are unusual remissions of dyspnea, particularly if the remission follows an embolus ; (4) if the murmurs are atypical or hard to hear; or (5) if there are unusual variations in symptoms with posture, e.g., faintness on stooping or dyspnea relieved by lying down. Right atria1 myxoma leads to failure of the right side of the heart that is usually rapidly progressive and unresponsive to treatment. Only 12 per cent of patients have no murmurs or rubs. Sounds resembling pericardial friction are heard in 20 per cent of patients and are possibly caused by tumor movement within the heart. Right atria1 myxoma may be confused with isolated tricuspid stenosis, Ebstein’s malformation, constrictive pericarditis, obscure myocardial disease and active rheumatic pericarditis. It seems reasonable to obtain angiograms showing the right atrium in patients suspected of having these rather rare diseases to exclude right atria1 myxoma. REFERENCES 1. NEWMAN, H. A., CORDELL, A. R. and PRICHARD, R. W. Intracardiac myxomas: Literature review and report of six cases, one successfully treated. Am. Surgeon, 32: 219, 1966. 2. GOODWIN, J. F. Diagnosis of left atria1 myxoma Lancet, 1: 464, 1963. 3. ALDRIDGE, H.E.and GREENWOOD, W.F. Myxoma of the left atrium. Bit. Heart J., 22: 189, 1960. 4. GOLDBERG, H. P., GLENN, F., DOTTER, C. T. and STEINBERG, I. Myxoma of left atrium: Diagnosis made during life with operative and postmortem findings. Circulation, 6: 762, 1952. 5. CRAFOORD, C. Panel discussion on late results of mitral commisurotomy. In: Henry Ford Hospital, Detroit, International Symposium on Cardiovascular Surgery: Studies in Physiology, diagnosis and Techniques, p. 202. Edited by LAMB, C. R. Philadelphia, 1955. W. B. Saunders. 6. BIGELOW, W. G., DOLAN, F. G. and CAMPBELL, F. W. The effect of hypothermia on the risk of surgery. In: Proceedings of the 16th Congress Internationale de Chirugie at Copenhagen, 1955,
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OF CARDIOLOGY
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F., SOBORN, .J. .J., ROBSON, G. B., BRAINM. and HILTGREN, H. Left atrial myxoma: successful removal with the aid of extracorporeal circulation. Ann. Surg., 147: 320, 1958. ELLIS, F. H., JR., MANKIN, H. T. and BURCHELL, II. B. Myxoma of the atrium: successful surgical treatment in two cases. M. Clin. ;Vorth America, 42: 1087, 1958. ~h’kTHEY, J. et al. Trois cas de myxoma intracardiaquc operes. Mim. Acad. chir., 85: 425, 1359. COHEN, A. I., MCINTOSH, H. D. and ORGAIN, E. S. The mimetic nature of left atria1 myxomas. Am. J. Cardiol., 11: 802, 1963. HORLICK, L. and MERRIMAN, J. E. Atria1 myxoma. Canad. M. A. J., 77: 582, 1957. LEFCOE, N. M., BRIAN, F. G. and MANNING, G. W. An opening snap recorded in a case of tumor of left atrium. ;VPW England J. Med., 257: 178, 1957. WASSERMIL, M., WARKENTIN, D. L. and RAVIN, A. Myxoma of the left atrium-phonocardiographic study of three cases. Circulation, 25 : 50, 1952. LEVINSON, J. P. and KINCAID, 0. W. Myxoma of the right atrium associated with polycythemia. ,Vew England J. Med., 264: 1187, 1961. SKANSE, B., BARA, N. 0. and WESTFIELD, T. A. Atria1 myxoma with Raynaud’s phenomenon as the initial symptom. Acta med. scandinau., 164: 321, 1959. VUOPIO, P. and NIKKIL;~, E. A. Hemolytic anemia and thrombocytopenia in a case of left atria1 myxoma associated with mitral stenosis. Am. J. Cardial., 17: 585, 1966. GOODWIN, J. F., KAY, J. M. and HEATH, D. Clinical pathological conference. Am. Heart J., 70: 239, 1965. ROPER, C. L., CAMP, F. A. and KEMPSON, R. L. Atria1 myxoma associated with fibroadenomas of the breast. Missouri Med., 62: 113, 1965. FRIEDBERG, S. L., OGNIBENE, A. J. and DOTO, W. R. Left atria1 myxoma and fatal abacterial pneumonia. J. Lancet, 85: 328, 1965. LOURIA, D. B., BLUMENFELD, H. L., ELLIS, J. T., KILBOURNE, E. D. and ROGERS, D. E. Studies on influenza in the pandemic of 1957 to 1958. II. Pulmonary complications of influenza. J. Gin. Invest., 38: 213, 1959. CURREY, H. F. L., MATHEWS, J. A. and ROBINSON, J. Right atria1 myxoma mimicking a rheumatic disorder. Brit. M. J., 1: 547, 1967. &GAL, B. L. Introduction to symposium on Echocardiography. Am. J. Cardiol., 19: 1, 1967. DICK, H. J. and MULLIN, E. W. Myxoma of the heart complicated by bloodstream infection: Staphylococcus aureus and candida parapsilosis. New York J. Med., 56: 856, 1956.
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