CLINICAL FEATURES OF ATRIAL · clinical features suggesting a generalized infection or general...

Thorax (1962), 17, 91.

CLINICAL FEATURES OF LEFT ATRIAL MYXOMABY

J. F. GOODWIN, C. A. STANFIELD,* R. E. STEINER, H. H. BENTALL,H. M. SAYED,t V. R. BLOOM, AND M. B. BISHOP+

From the Departments of Medicine, Radiodiagnosis, and Surgery, Postgraduate Medical School andHammersmith Hospital, London

(RECEIVED FOR PUBLICATION AUGUST 17, 1961)

Myxoma of the left atrium is the commonestprimary cardiac neoplasm and numerous caseshave been reported (Leach, 1947; Prichard, 1951).Criteria suggested for the diagnosis usuallyemphasize the similarity to mitral stenosis, theimportance of postural changes in symptoms andsigns, and the occurrence of syncope, arrhythmia,persistent heart failure, and embolic phenomena.

Left atrial myxomas have been confused withinflammatory disease, such as lupus erythematosus,Hamman-Rich syndrome, " myocarditis," subacutebacterial endocarditis, or even acute rheumaticfever (Skanse, Berg, and Westfelt, 1959 ; Lekisch,1957). Hyperglobulinaemia has been reported(Skanse et al., 1959; Evans, 1959; Frankenfeld,Waters, and Steiner, 1960; MacGregor andCullen, 1959), but has not been emphasized asmuch as the haemodynamic and embolic aspectsof the disease.The object of this paper is to present four

patients proven clinically (three of whom hadsuccessful operations), with special reference toclinical features suggesting a generalized infectionor general systemic disease. Particular attentionis paid to changes in the serum proteins and tothe physical signs. The haemodynamic effects,angiographic studies, the pathology, and the resultsof successful surgical removal are described.

PATIENTS STUDIED AND METHODSOF INVESTIGATION

There were four patients; one man aged 63 years,and three women aged 48, 47, and 23 years. Clinicalstudies, phonocardiography, and cardiac catheter-ization were performed in all four, and angiocardio-graphy in three. Selective angiograms were obtainedof the right and left sides of the heart in one patientand of the right side only in two. The erythrocytesedimentation rate and serum proteins were studied

*Advanced research fellow of the American Heart Association.tLecturer in thoracic surgery, Ein Shams University, Cairo,

U.A.R.$Nuffield Foundation research fellow in cardiac pathology.

repeatedly before and after operation in the threepatients who came to surgery.

PATIENT 1.-A. G., a Lithuanian woman, aged 48,was a poor historian, but denied rheumatic fever orchorea. In 1957 she was found to have atrial fibrilla-tion, and following this she complained of generalmalaise, abdominal pain. dyspnoea on effort,generalized limb pains, and night sweats. In 1958she developed thyrotoxicosis which resolved onmedical treatment. The atrial fibrillation thenreverted to sinus rhythm, but subsequently relapsedin 1959. At this time a murmur suggestive of mitralvalve disease was heard, and later she developedsubsternal pain resembling angina of effort.

First Hospital Admission.-She was admitted toHammersmith Hospital in October, 1959, for investiga-tion. On examination she was a sallow, ill-lookingwoman. Gross clubbing of the fingers was noted:it had not been present four months previously. Thepulse was 100/minute, irregular from atrial fibrilla-tion, and the blood pressure was about 110/75 mm.Hg. The apical first heart sound was accentuated,and there was a short grade 2 mitral diastolic murmurand an early soft opening snap. The second heartsound was normal. There was no splenomegaly orlymphadenopathy.Serum Proteins.-These were abnormal, the

albumin level being 2.5 g.% and the globulin 5.3 g.%(Fig. 1). The haemoglobin was 12 g.0/. The whiteblood cell count was 6,000/c.mm. Blood cultureswere repeatedly negative. The erythrocyte sedimenta-tion rate was 83 mm./hour (Westergren).

Electrocardiographv.-An electrocardiogram wasnormal before the development of atrial fibrillation(Fig. 2).Radiography.-A chest radiograph showed enlarge-

ment of the right ventricle and left atrium, but noevidence of pulmonary vascular disorder, heart failure,or mitral valve calcification.

Progress. The patient remained febrile and ill,and a diagnosis of subacute infective endocarditis ofthe mitral valve was made. However, she made noresponse to treatment with full doses of penicillin

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J. F. GOODWIN AND OTHERS

A. G. A. G.

Patient 2 W.S.

Patient 3 S.P.

Patient I A.G.

Patient 4 J-J.

4-3 26

25 53

2-2 36

3-6 41FIG. 1.-Two random estimations of serum

proteins in each of the four patients. Thestudies were made before operation inPatients 2, 3, and 4. In each case the serumglobulins, usually the gamma fractions, are

2-9 3-3 raised. and the variability of the electro-phoretic pattern in the same patient isapparent. A= albumin(g. %); G globulin(g. %).

FIG. 2.-Eleatrocardiograms from the fourpatients. Patient I hts a normal ventricularbalance, but Patients 2 and 3 show grade 2,

2-9 6-0 and Patient 4 shows grade 3, right ventri-cular hypertrophy. T wave inversion in V5and V6 is notable in Patient 3 and is attri-

L butable to the effects of digitalis and rightventricular hypertrophy.

26 38

11 III VR V4R VI VS V7

Patient I A.G.

Patient 2 L W.S. t-- -e f

Patient 3 S.P. -L4 , 1

Patient 4 J.J. -4. &n ".-,1_

FIG.2 I sec.

FiG. I

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CLNICAL FEATURES OF LEFT A TRIAL MYXOMA

and streptomycin forwere considered, andmyxoma was suggesteextensive investigationillness, and she wasdi

out-patient departmenl1950. In April, 1960,cough, and rusty sputankles. Substernaldyspnoea.

Second Hospital Aito hospital in May, 1looked ill and was felfibrillation was still p

pressure was now 3Pulmonary valveclointensity and was eat

monary ejetion murtnow a grade 3 systolimid-diastolic murmur

previously. Therewright lung, but the liv4and there was no oedefingers pcrsisted.

Serum Proteins.-albumin levels rangingfrom 4.4 to 4.6 g.% (10 g.% and the whitbThe erythrocyte sedirr(Westergren).

Radiography.-A clment of the right ventatrium, with signs ofhypertension. Smallinitially present but cl

Cardiac Catheteriz,poned or abandonedoedema. On the thircpressure was 85/23 (monary venous "wed(Table I).

RESULTS OF RIGHT HEATR

Patient I

Arterial 0., 92(%/)

Cardiacoutput(1. imin.)

Rightventricle(mm. Hg) 75 7

Pulmonaryartery(mm. Hg) 85 23 (43)+

Pulmonarycapillary"wedge" 40 15 (28)* At Bristol Royal Hnsiit

pressures are shown in pa

six weeks. Other conditions Angiocardiography.-- A venous angiocardiogramthe possibility of left atrial showed a small filling defect of doubtful significance

d by Dr. C. C. Booth. After in the left atrium. The arteries of the right lungl no cause was found for her filled less well than those of the left; the pulmonaryischarged for observation in the veins were not visualized on the right side and weret at her own request in January, thought to be occluded.she developed severe dyspnoea, Progress.-On June 3, 1960, the patient developed

hum, with slight swelling of the an infarct in the right lung and appeared to betightness was associated with deteriorating. The diagnosis was now considered to

rest between a left atrial myxoma and severe mitraldmission.-She was readmitted insufficiency following bacterial endocarditis. We960. On examination she still decided to explore the left atrium, but the patient:rile (97.5' to 99.5' F.). Atrial died before this could be done)resent, and the jugular venous Necropsy.-The heart, which weighed 420 g.,cm. above the sternal angle. contained in the left atrium a pedunculated myxomasure was greatly increased in which arose from the wall of the atrial septum a fewrly in timing. A grade 2 pul- millimetres from the posterior rim of the fossa ovalis,mur was heard and there was below the entrance of the pulmonary veins andic murmur at the apex, but the slightly above the coronary sinus. It was firmlywas softer and longer than attached by a narrow pedicle. 8 mm. in diameter, from

tas dullness at the base of the which it expanded into a lobulated mass of greyish-er and spleen were not enlarged pink, gelatinous material 4 cm. in its widest diameter.-ma. The gross clubbing of the It hung down through the mitral valve ring, and the

free end of the mass, which lay mainly in the confines

These remained abnormal, of the mitral valve, had become converted into a

from 2.3 to 3.3 g./' and globulin twisted, pale, cheesy material in which there were fine'Fig. 1). The haemoglobin was flecks of calcium. The atrial surfaces of the mitralFg1).od Thel haemoguobin ws0valve cusps in contact with this material had becomeenblood cell count 7,000/c.mM. abraded, and two of the chordae to the anterior cuspientation rate was 16 mm./ hour were severed. The valve ring was slightly dilated,

but the valve was otherwise normal. The left atriumhest radiograph showed enlarge- and right ventricle were both dilated and hyper-;ricle, pulmonary artery, and left trophied. The left ventricle was moderately dilated,pulmonary arterial and venous but the wall was of normal thickness (Fig. 3 a and b).bilateral pleural effusions were PAnENT 2.-W. S., a man aged 63 years, had been[eared with treatment. well (with no history cf rheumatic fever or previousation.-This was twice post- cardiovascular disease), until he developed rapidlyowing to threatened pulmonary increasing exertional and paroxysmal nocturnal dys-I occasion the pulmonary artery pnoea 28 months before admission to Hammersmithmean 43) mm. Hg, but a pul- Hospital in September, 1960. Two years earlier he hadIge pressure" was not obtained been in sinus rhythm with an apical presystolic

thrill, accentuated first heart sound, and increase inintensity of pulmonary closure. A pansystolicmurmur was heard at the apex, and there was a

TABLE I diastolic rumbling murmur with presystolic accentua-ART CATHETERIZATION IN LEFT tion. No opening snap was heard.UAL MYXOMA In April, 1960, the patient had experienced five

Patient 4 episodes of vertigo and blurring of vision, followedPatient 2 Patient -- a few seconds later by loss of consciousness for up

3* (l)t (2) to 10 minutes, usually associated with urinary

89 - 87 - incontinence. None of these episodes was observedby a doctor, but they were apparently related to

30 - 46 - changes in posture. There were no residual neuro-

logical symptoms or signs. During the two years of80 10 100 20 - 89 7 illness preceding his admission, he had lost 14 lb.

in weight.90 30 (47) 75 38 - (39) 89 35 (50) Examination on admission to Hammersmith

Hospital revealed a pale, dyspnoeic, elderly man with(20) (35) (19) 32/22 (25) slight peripheral cyanosis, but no definite clubbingtal. t At King's College Hospital. + Mean of the fingers or toes. The pulse was regular atrentheses. + 100/minute, the blood pressure was 95/70 mm. Hg.

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FIG. 3a FIG. 3b

FIG. 3.-Patient 1: (a) Photomicrograph of the myxoma showing the attachment of the pedicle (P) to the left atrial wall (LA), H. and E. > 8-4.(b) High-power view of the myxoma, showing the characteristic cell with plump nucleus and processes extending irregtularly into the myxoidstroma in which there is a scattering of red blood cells, H. and E. 370.

and he was febrile (97° to 100' F.). The jugularvenous pressure was raised to 10 cm. above the sternalangle with a prominent "a" wave. There were

crepitations at both lung bases. The cardiac impulsewas not localized, but there was a right ventricularheave. At the apex there was a presystolic thrilland a full-length diastolic murmur with presystolicaccentuation; the first sound was accentuated andfollowed by a grade I pansystolic murmur. No openingsnap was heard, but the pulmonary component ofthe second sound was accentuated. The liver edge was

palpable 5 cm. below the right costal margin, but thespleen was not felt. The peripheral arterial pulseswere all present but of small volume, and there was

no oedema.Serum Proteins. These were repeatedly abnormal

during the course of the illness, and were recordedas follows: albumin 3.3, 3.0. and 3.6 g.%; globulin4.4. 4.3. and 4.1 g.0/0 (Fig. 1). The haemoglobin was

11.5 g. /. white blood cell count 7,000/c.mm., with a

rornial differential count. The red blood cells were

hypochromic. The blood urea was 49 mg. "I andthe erythrocyte sedimentation rate was 10 mm./hour(Westergren).

Electrocardiographs. An electrocardiogramshowed sinus rhythm and grade 2 right ventricularhypertrophy (Fig. 2).

Radiographv. A chest radiograph showedenlargement of both ventricles and of the pulmonaryartery, but the left atrium was only slightly enlarged.There were signs of pulmonary arterial anid venoushypertension.

Progress. On the eighth day after admission thepatient developed fever to 101° F., which persistedfor three days. He was found to have microscopichaematuria and the blood urea rose to 60 mg. 00.but blood cultures were repeatedly sterile. Thesedimentation rate was now 32 mm./hour. On theeleventh day after admission penicillin. streptomycin.and probenecid were started as treatment for subacutebacterial endocarditis and continued for six weeks.

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CLINICAL FEATURES OF LEFT ATRIAL MYXOMA

It was considered that the mitral valve was infected.The blood urea reached a maximum value of 77 mg. %,but had fallen to 47 mg.% three weeks after admis-sion. The sedimentation rate rose to 34 mm./hour,but fell after one month's treatment to 10 mm./hour.Haematuria did not persist after a fortnight inhospital.

Three weeks after his admission the cardiacmurmurs were found to have changed, and the apicalpansystolic murmur was now cf grade 3 intensity andwas transmitted to the axilla; the mid-diastolicmurmur was still present, but was softer and shorter,and the presystolic accentuation and thrill had dis-appeared. The erythrocyte sedimentation rate was60 mm./hour on the sixty-third day after admission,and the patient did not seem to have benefited fromthe treatment for bacterial endocarditis.

In view of the changing murmurs, failure to respondsatisfactorily to treatment, persistently high sedi-mentation rate, abnormal proteins, and fever in theabsence of positive blood cultures, the possibility of aleft atrial myxoma was considered.

Cardiac Catheterization.-Catheterization of theright heart was performed two months after admis-sion. The cardiac output was 3 1./minute, pulmonaryartery pressure 90/30 mm. Hg, and mean pulmonaryartery " wedge pressure " 20 mm. Hg with prominent" v " waves, suggesting mitral insufficiency (Table 1).

Angiocardiography revealed a filling defect in theleft atrium of doubtful significance. This filling defectwas lobulated and of a type not previously seen inour angiographic studies in mitral valve disease. Itresembled that found in our first patient, and wassimilar to the appearances illustrated by Goldberg.Glenn, Dotter, and Steinberg (1952) and by Steinberg.Dotter, and Glenn (1953) in cases of left atrialmyxoma. A retrograde left ventricular angiogram wasperformed which showed marked reflux of contrastmedium into the left atrium, indicating severe mitralincompetence; it also confirmed the lobulated fillingdefect in the atrium produced by the myxoma. Onseveral films the tumour appeared to be mobile andto prolapse from the left atrium into the left ventricleand vice versa (Fig. 4 a and b).

Operation (Mr. L. L. Bromley and H. H. B.).-Theright atrium was exposed through a right antero-lateral thoracotomy in the fourth intercostal space.Routine cannulations of the left common femoralartery and the superior and inferior venae cavae wereperformed, care being taken to site the caval cannulaewell posteriorly. Normothermic cardio-pulmonarybypass was instituted.The tumour was approached through an incision

placed anteriorly in the right atrium. The inter-atrialseptum was incised above the fossa ovalis and theincision was gradually enlarged as the soft g2latinous

FIG. 4.-Patient 2. Retrograde left ventricular angiogram (lateral projection): (a) contrast medium spreading back into the left atrium fromthe left ventricle, indicating mitral incompetence; there is a lobulated filling defect in the left atrium due to the myxoma (arrowed);(b) half a second later the filling defect can be seen in the left ventricle, due to prolapse of the myxoma through the mitral valve.

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tumour presented. There was a small (1 cm.) pediclesituated near the superior margin of the fossa ovalis.The pedicle was excised with the complete thicknessof the septum. The tumour was graduallydelivered, disimpacting that part which had prolapsedthrough the normal mitral valve. The impressioncaused by the mitral valve ring was clearly seen as aconstriction. The aorta was clamped to preventthe possibility of tumour embolus. The main bulkof the tumour was delivered intact, but some frag-ments were detached. These fragments were removedby sucking; the left atrium and left ventricle werewashed with normal saline and sucked dry severaltimes, all products of suction being discarded.The left ventricle and left atrium were allowed to

refill with blood and the incision in the atrial septumwas repaired.The total period of aortic occlusion was six minutes,

and of cardio-pulmonary bypass 21 minutes. Pressureswere recorded before and after removal of the tumourand are set out in Table II.

TABLE IXVASCULAR PRESSURES BEFORE AND AFTER REMOVAI

OF LEFT ATRIAL MYXOMA

Pulmonary Artery Left Atrium Systemic Artery(mm. Hg) (mm. Hg) (mm. Hg)

Patient Before After Before After Before After

2 60/20(45) 55/30(37) 40 20 18 10 70'40 90 -3 55130(42) 60130(38) 60/18 20 10 100160(78) 100160(78)4 42/35(22) 38/18(25) 30/12 20/10 82156(68) 115i'62(80)

Mean pressures are shown in parentheses.

Pathology. The tissue removed at operationweighed 54 g. and consisted of several fragments anda larger mass, 7 x 4 x 3 cm. in its widest diameters,which comprised the bulk of the tumour. The smallerfragments were mainly soft and gelatinous. At oneedge of the main mass was a narrower, somewhatfibrotic pedicle, 1 cm. in diameter, and 3 cm. awayfrom this edge of the myxoma there was a slightconstriction made by the mitral valve ring. Thebulbous free end was presumably that portion whichhad been situated mainly in the left ventricular cavity(Fig. 5).

Post-operative Course.-This was uneventful apartfrom hypotension during the first 48 hours. Theapical systolic murmur became much reduced inintensity, but signs of pulmonary hypertensionpersisted. Subsequently, the patient improved greatly,the dyspnoea disappeared, he put on weight, and hisfever resolved completely. The serum proteinsbecame normal (Fig. 6).

PATIENT 3.-S. P., a woman aged 23 years, first noteddyspnoea on climbing stairs and a persistent coughfollowing a bout of bronchitis in 1958. In November,1960, she was referred by Drs. Davies and Barritt, ofBristol, who suspected the presence of myxoma ofthe left atrium. She had previously been well andhad no history of rheumatic fever.

FIG. 5.-Patient 2. Myxoma removed at operation

In February, 1959, she was found to have a low-grade fever, an apical diastolic murmur, and anerythrocyte sedimentation rate of 36 mm./hour. Adiagnosis of active rheumatic carditis was made, andshe was sent home to rest for two months. BetweenAugust, 1959, and February, 1960, the erythrocytesedimentation rate varied from 14 to 25 mm./hour.In June, 1960, she was admitted to the Bristol RoyalHospital because of exertional dyspnoea, fatigue,cough, fever, tachycardia, and oedema of the ankles.On examination she was thin and ill with evidenceof pulmonary hypertension. Systolic and diastolicmurmurs and a third heart sound were heard at thecardiac apex. Catheterization of the right heartrevealed a pulmonary artery pressure of 75/30 mm.Hg and a pulmonary artery "wedge pressure " of35 mm. Hg (Table 1). During catheterization thepatient developed pulmonary oedema and hypotensionand was gravely ill for several days. She made aslow and partial recovery, but remained in hospitaluntil September, 1960. During this time the low-gradefever and tachycardia persisted, but the serumglobulins were not raised.She was transferred to Hammersmith Hospital in

November, 1960, complaining of severe dyspnoea andorthopnoea; she had lost 30 lb. in weight during thetwo years of her illness.On examination she was afebrile, but appeared pale.

wasted, ill, and dyspnoeic. Pale, cold extremities anda small pulse volume indicated a low cardiac output.The pulse was regular at 120/minute and the bloodpressure was 95/70 mm. Hg. Crepitations were heardat both lung bases. Jugular venous " a " and " v "'waves rose to 5 cm. above the sternal angle. Therewas a right ventricular heave but the left ventricle

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Before Operation After Operation

Patient 2 W.S.

Patient 3 S.P.

Patient 4 J.J.

A. 30G. 4-3

A. 29G. 3.3

A. 26G 38

A. 38G. 37

A. 46G. 29

A. 43G. 2-6

FIG. 6.-Serum proteins before and after operation. In all three patients the abnormal albumin globulin ratio became norma!. A=albumirn(g. %); G =globulin (g. %).

was not enlarged clinically. The first heart soundat the apex was accentuated, and there was a grade 3apical pansystolic murmur with a loud third heartsound which was heard maximally over the rightventricle and more softly towards the axilla. Noapical diastolic murmur was heard. In the pulmonaryarea a grade 1 ejection systolic murmur with ejectionclick was followed by a narrowly split second withaccentuation of the pulmonary component. The liverand spleen were not felt.Serum Proteins.-These became abnormal. On the

third day after admission the albumin was 4.3 g.%and the globulin 2.6 g.%, but on the twenty-ninthday after admission the albumin was 3.2 g.%/ andthe globulin 3.3 g.% (Fig. 1). The haemoglobin was12.3 g.%, white blood cell count 8,000/c.mm., witha normal differential count. The urine was normal.Blood cultures were repeatedly negative.

Electrocardiography. -- An electrocardiogramshowed sinus rhythm with slight atrial and grade 2right ventricular hypertrophy (Fig. 2).Radiography.-A chest radiograph showed enlarge-

ment of the right ventricle, pulmonary artery, andboth atria. Horizontal costophrenic lines, indicatingpulmonary venous hypertension, were present in both

lower lung fields, and there was an effusion at theright base (Fig. 7 a-d).

Isotope studies of regional pulmonary blood flowby Dr. C. T. Dollery showed reduced perfusion tothe lower portions of the lungs, typical of left atrialand mitral obstruction.

Progress. - The dyspnoea gradually increaseddespite treatment with rest, digitalis, and diuretics.There was pleuritic pain at the base of the right lung.suggesting pulmonary infarction. The apical systolicmurmur was noted to vary in intensity from day today, and slight clubbing of the fingers, absent onadmission, was noted a month after the patient hadbeen in hospital.Her critical illness and the history of pulmonary

oed_mra during previous cardiac catheterizationcontraindicated angiocardiography to confirm thediagnosis of left atrial myxoma, and because theclinical diagnosis seemed almost certain, operationwas carried out 37 days after admission to hospital.

Operation (H. H. B. and Mr. L. L. Bromley).-Theoperation was performed in a similar manner to thaton Patient 2 under normothermic bypass. On openingthe chest the right lung was found to be stiff andthe pulmonary lymphatics distended. Both atriawere enlarged and tense. A myxoma was found to

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extend from a stalk attached near the fossa ovalisthrough a normal mitral valve. The details of thetechnique were almost identical with those in theprevious patient.

The period of aortic clamping was seven minutesand the duration of bypass 28 minutes.

Diagnostic pressures were recorded before andafter removal of the tumour (Table 1I).

Pathology. The total weight of the tissue removedwas 48 g. In addition to several small gelatinousfragments, there was a similar large tumour mass witha narrow pedicle. 7 mm. in diameter. a smaller atrialportion being separated by a fairly sharp constrictionfrom a larger. irregularly shaped ventricular portionmeasuring 4 x 3 cm.

Post-operative Course. This was unremarkableexcept for transient hypotension and bigeminal

b

FIG. 7.-Patient 3. Chest radiographs before and after operation: (a) pre-operative postero-anterior film showing a right basal effusion, andenlargement of the main pulmonary arteries indicating pulmonary arterial hypertension; signs ot venous hypertension are not well seen(see text); (b) pre-operative lateral film showing right ventricular and left atrial enlargement; (c) post-operative postero-anterior filmshowing reduction in size of the main pulmonary arteries and resolution of the right basal effusion; (d) post-operative lateral film showingreduction in size of the lzft atrium.

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rhythm. The apical systolic murmur and third sounddisappeared. The patient subsequently made anuninterrupted recovery and gained 35 lb. in weight.The jugular venous pressure became normal andsigns of pulmonary hypertension regressed. Theeffusion at the base of the right lung cleared (Fig. 7c).It was considered to have been due to obstructionof the right lower lobe pulmonary veins by thrombosisattributable to the low cardiac output and the severepulmonary hypertension and vascular disorder. Theserum proteins returned to normal (Fig. 6).

PATIENT 4.-J. J., a woman aged 47, was healthyuntil nine months before her admission to King's Col-lege Hospital on January 20, 1961. During that timeshe developed fatigue, dyspnoea, lethargy, and generalmalaise, with sweating at night. On several occasionssyncopal attacks followed sudden turning in bed. Shehad lost 28 lb. in weight. There was no history ofrheumatic fever, and when she was examined in 1954no abnormality had been found.A left atrial myxoma was suspected by Dr. Bruce

Pearson and Mr. W. P. Cleland on the basis of thehistory and signs which were suggestive, but nottypical, of mitral valve disease, heart failure of rapidonset, and syncopal attacks. Cardiac catheterizationshowed pulmonary venous and arterial hypertension(Table I). She was transferred to HammersmithHospital on February 20. 1961.

On examination she was an ill woman withorthopnoea, obvious loss of weight, pallor, and slightclubbing of the fingers. Arterial pulses were normal.but the jugular venous pressure was raised to 5 cm.above the sternal angle with a prominent " a " wave.The blood pressure was 105/70 mm. Hg. The cardiacimpulse was right ventricular in type with a sternalheave. The first heart sound was accentuated andthere was a short low-pitched early diastolic soundand short soft presystolic murmur at the apex. Therewas no opening snap. The murmurs and sounds didnot change with posture. The pulmonary closuresound was accentuated and the split was narrow.There were crepitations at the lung bases, and theliver, but not the spleen, was enlarged.Serum Proteins.-These were abnormal. the

albumin levels ranging from 2.2 to 2.6 g.% and theglobulin from 3.6 to 3.8 g.% (Fig. 1). The haemo-globin was 10.5 g.%, the white blood cell count rangedfrom 6,000 to 12,000 per c.mm., and the erythrocytesedimentation rate from 15 to 22 mm./hour.

Electrocardiography. - An electrocardiogramshowed grade 3 right ventricular hypertrophy andlow voltage (Fig. 2).Radiography.-A chest radiograph showed enlarge-

ment of the right ventricle, pulmonary arteries, leftatrium, and possibly the left ventricle. There wasmarked pulmonary arterial and venous hypertension.

FIG. 8.-Patient 4. Pre- and post-operative postero-anterior cnest radiographs: (a) pre-operative, showing enlargement of the heart and themain pulmonary arteries and an effusion and consolidation at the right base; the upper lobe vessels are distended, but signs of venoushypertension are not well seen; (b) post-operative: the right base is now clear and the main pulmonary arteries are smaller.

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There was no evidence of calcification in the region ofthe mitral valve. Consolidation and an effusion atthe right base were probably due to pulmonaryinfarction (Fig. 8).

Cardiac Catheterization and Selective PulmonaryA rteriography.-This demonstrated a pulmonaryartery pressure of 89/35 (mean 50) mm. Hg and awedge pressure of 32/22 (mean 25) mm. Hg (Table I).The main pulmonary arteries were greatly enlargedand the basal segmental branches tortuous andnarrowed, especially on the right side. The leftatrium was enlarged and a lobulated filling defectwas seen within it. On several films the defect wasseen to move from the left ventricles to the left atria,indicating its mobility through the mitral valve. Theright lower lobe pulmonary vein failed to fill withcontrast medium, indicating obstruction by thrombusor myxoma (Figs. 9 a and b and 10 a-e). The reten-tion of contrast medium in the right lower lobepulmonary arteries indicated obstruction to flowthrough that lung segment.

Operation (Mr. W. P. Cleland).-The chest wasopened through a median sternotomy and operationcarried out using normothermic cardio-pulmonarybypass. A soft lobulated myxoma was found attachedto the region of the fossa ovalis (Fig. 11).

Details of the subsequent procedure were similar tothose in the previous two patients.The perfusion time was 41 minutes, and three

periods of aortic clamping of two minutes, twominutes, and seven minutes were required.

Diagnostic pressures were recorded before and afteroperation, and showed a rise in systemic, a fall inleft atrial, but little fall in pulmonary artery, pressures(Table II and Fig. 12).Pathology.-The total weight of the myxoma

removed was 37 g. It was a discrete rounded mass4 x 3 x 2 cm. in its widest diameters, and lacked aconstricting ring, suggesting that it had been mainlyintra-atrial. The pedicle was small, 5 mm. in diameter,and the mass mushroomed out from its point ofattachment with a more rounded, lobular surface.The colour was pinkish yellow and noticeably palerthan the previous examples. It differed also in thatthere was a discrete central area of calcification 1 cm.in diameter.

Post-operative Course.-This was uneventful exceptfor pulmonary infarction in the immediate post-operative period. Two months after the operationthe patient had lost all her symptoms and had gainedweight. The jugular venous pressure was normal,and a third heart sound, but no murmur, was heard atthe apex. Pulmonary valve closure remained slightlvaccentuated, but the right basal shadow cleared. Theserum proteins had become normal, the albumin being4.3 g.% and globulin 2.6 g.% (Fig. 6).

SPECIAL FEATURES OF THE DISEASESYMPTOMS.-Table III sets out the symptoms

in the four patients described. Dyspnoea,

orthopnoea, fatigue, and loss of weight werecommon to all. None had a history of rheumaticfever. The emphasis in the symptomatology wason pulmonary hypertension and a generalizedtoxic infective process more than on syncope oremboli. Syncope, however, occurred in twopatients, but was related to posture in only one.In one patient (who also had a renal embolism)syncopal attacks may have been due to smallcerebral emboli.

TABLE IIISYMPTOMS IN LEFT ATRIAL MYXOMA

Symptoms

DyspnoeaOrthopnoeaParoxysmal nocturnal dyspnceaAcute pulmonary oedemaCoughHaemoptysisPalpitationChest painOedemaFatigueWeight loss (lb.)Syncope

, . / _

Patient

2 3 4

+ ± ++ -4- + 4-? + + o+ 0 + 0+ 0 4- ++ 0 0 -+(A.F.) + 0 0+ 0 4-+ 0 + 0+ + 1 +

51 14 30 280 Spon- 0 Exertion,

taneous posture

FIG. 9.-Patient 4. Arterialphase of pulmonary arterio-gram: (a) postero-anteriorprojection showing enlarge-ment of the main pulmonaryarteries with narrowing ofthe segmental branches tothe lower zones: those atthe right lower zone aretortuous; (b) line drawingof the right pulmonaryartery: U.L.P.A.=pulmon-ary artery to upper lobe;L.L.P.A. pulmonary arteryto lower lobe.

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U. L.

P V~.

L.A

UL.

PA

Fi(i. 10e

FIG. 10.-Patient 4. Venous phase of pulmonary arteriogram:(a) postero-anterior projection, showing an irregular fillingdefect in the left atrium due to the myxoma (arrowed); contrastmedium does not fill the right lower lobe veins but is retained inthe tortuous right lower lobe arteries, indicating obstruction toblood flow in the right lower lobe; (b) simultaneous lateralprojection showing the myxoma lying in the left atrium (arrowed);(c) postero-anterior projection one second later, showing thatthe myxoma (arrowed) has prolapsed through the mitral valveinto the left ventricle; (d) simultaneous lateral projection;(e) line drawing for 9a showing position of upper lobe pulmonaryveins (U.L.P.V.) and lower lobe pulmonary artery (L.L.P.A.).(LA=left atrium.)



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FIG. 11.-Patient 4. View of right atrium showing myxoma partlydelivered through the atrial septum.

Before

CLINICAL SIGNS (Table IV).--Fever was presentin all patients and was usually low grade (990 F.),but occasionally temperatures of up to 101° F.were recorded. All the patients looked ill,haggard, and pale, and had obviously lost weighit.Splenomegaly was never found, but the liver wasenlarged in two patients. Clubbing of the fingerswas found in three patients, and was gross in one.As far as we are aware this has not previously

been described. Judging by the slight degrees inthree of our patients, it might easily have beenmissed in other reported cases, and it was notmentioned in MacGregor and Cullen's (1959)patient. The cause is quite unknown ; our patientsdid not have arterial desaturation, pulmonarysepsis, or hepatic or gastrointestinal disease. Itis possible that arterio-venous shunts occurred inthe lungs as a response to the vascular obstruction,and we have very occasionally noticed clubbing

After

100-

B.A. 50 -

0-

100-

P.A. 50 -

100-

L.A.50-

0

100-

O -

FIG. 12.-Patient 4. Systemic arterial (B.A.), pulmonary arterial (P.A.), and left atrial (L.A.) pressures immediatelybefore and after remnoval of left atrial myxoma. The brac-hial artery pressure has risen, and the left atrial has fallen,indicating a decrease in pulmonary vascular resistance and an increase in cardiac output following removal ofthe obstruction (pressure in mm. Flg).

102

100,

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f-,./"'\i -\

0.

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TABLECLINICAL SIGNS IN LE]

Clinical Signs

FeverPallorClubbingElevated jugular venous pressureRhythm

Blood pressure (mm. Hg)Pulmonary rilesRight ventricular enlargementMitral first sound accentuatedSecond sound narrowly splitand pulmonary closureaccentuated

Opening snapThird heart soundApical murmurs: systolicApical murmurs: diastolic

Variable murmursHepatomegalySplenomegalyPulmonary infarctionSystemic embolism

SilaA

?c

in patients with mitral stebacterial endocarditis orbe of interest to knowarteries become enlarged irbut these were not studie4Apart from these I

generalized systemic diso]were in the cardiovasculapulmonary and left atrial hin all, as were signs suggestA diastolic murmur suggewas heard in three patient,from time to time, andoccurred in three patients.Undoubted embolism

patient, who was in sinfibrillation in only one oti

PHONOCARDIOGRAPHY (Fiteristic features were a ,

sound, a high-pitched paan accentuated pulmonasecond heart sound. Anrecorded, although it hadpatient. A mid-diastolic rin this first patient, andrecorded in the fourth paearly diastolic sound wasbe a third heart sound, bgram might have beenmurmur.The wide splitting of the

patients would be consisteiatrium and delayed fillingto the space-occupying 1I

IV murmur was presumably due to mitral incompe-FT ATRIAL MYXOMA tence resulting from distortion of the mitral valve

Patient by the tumour.1 2 3 4 After operation the first heart sound became

normal in Patients 3 and 4, the mid-diastolico + t + murmur disappeared in the fourth, and the+ + ° + + pansystolic murmur disappeared in the third.inus; Sinus Sinus Sinus Accentuation of pulmonary closure persisted inatera.F. all patients, and Patient 2 retained the wide0/80 95 '70 95/70 105, 70 splitting of the first sound and a soft systolic+ + + + murmur.0 + 0 + Owing to the variability of the murmurs,+ + + + phonocardiography presented some difficulties,+ 0 0 0 and the findings were not always consistent with+ ° + o those on auscultation.

(thrill) ELECTROCARDIOGRAPHY (Fig. 2).-There were± + + 0 no characteristic features of the disorder, the0 + 00 0 0 0 appearances being those of left atrial and right're- Renal 0 0 ventricular enlargement characteristic of any lesion)ral of the left side of the heart producing left atrial

and pulmonary arterial hypertension.nosis in the absence of The graphs of Patient 1 were of interest,other cause. It would however, in showing no evidence of ventricularwhether the bronchial imbalance or left atrial embarrassment despiten patients with myxoma, severe pulmonary venous and arterial hyper-d in Patient 1. tension.features suggesting a RADIOGRAPHY OF THE CHEST.-The changesrder, the striking signs were similar to those found in severe mitralLr system. Evidence of stenosis, with evidence of pulmonary arterialiypertension was present hypertension, enlargement of the right ventricleting mitral valve disease. and main pulmonary arteries, and narrowing ofsting mitral obstruction the segmental arteries to the lower portions ofs. The murmurs varied the lungs. Pulmonary venous hypertension wasI pulmonary infarction shown by horizontal costophrenic lines and hilar

shadows suggesting incipient pulmonary oedema.occurred in only one Pulmonary infarction was present in threeius rhythm, and atrial patients but disappeared after operation. It washer patient. due to obstruction to pulmonary veins, probablyvg. 13 a-d).-The charac- by venous thrombosis, rather than to venouswidely split first heart occlusion from myxomatous tissue.Lnsystolic murmur, and The left atrium was enlarged in all the patients,ry component of the but no intracardiac calcification was seen.opening snap was not ANGIOCARDIOGRAPHY.-In each patient thebeen heard in our first examination showed a lobulated filling defectmurmur was also heard lying in the left atrium. This was leastI was both heard and impressive in our first patient, but in thettient. In Patient 3 an fourth it was obvious, and in different filmsclinically considered to appeared in the left atrium and left ventricleut on the phonocardio- alternately. This movement of the myxomaa short mid-diastolic through the mitral valve was also seen in Patient 2.

We now regard these appearances as diagnosticefirst heart sound in all of myxoma, for we have never seen them producednt with an enlarged left by thrombus in a large number of angiograms inof the left ventricle due mitral valve disease. We consider that a goodesion. The pansystolic pulmonary arteriogram should demonstrate a

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2

M.D.M.

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PA. ,,-

H.F.

M.A...___v...........-_---- * --- - w § vw ww - s . --------- ---- ----B0. . . .

H,F

FIG. 13.-Phonocardiograms before and after operation: Patient 3 (a) high-frequency recordings from the left sternal edge and mitral areabefore operation showing widely split first sound (0-06/sec.), soft pansystolic murmur, and early diastolic vibrations (MDM); pulmonaryclosure is a:centuated; (b) high-frequency recordings from pulmonary artery and mitral areas after operation: the first heart sound isnow single and the diastolic vibrations have disappeared.

-.A hill II. _ .

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.;1 y mv..000,1/

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2

L.S.E. !im\I r { -- -----7---

H.F. If

M.A.

H.F.

I M.D.M._ ~

A A

uJ

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M. A.

H.F.

A.A- P O N N M--W.-P-0- 4 iN #

Fiu;. 13d

FIG. 13.-Phonocardiograms before and after operation: Patient 4 (c) high-frequency recordings from the left sternal edge and mitral area

before operation showing widely split first sound (0-061sec.) and soft mid-diastolic murmur; pulmonary closure is accentuated; (d) high-frequency recordings from pulmonary artery and mitral areas after operation; the first heart sound is now single and the mid-diastolicmurmur has disappeared. P.A.=pulmonary artery; M.A.=-mitral area; L.S.E.=left sternal edge; H.F.=high frequency; I =firstheart sound; 2 ==second heart sound; A2= aortic valve closure; P2= pulmonary valve closure.

H

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myxoma satisfactorily. A left ventricular angio-gram is only likely to show the tumour when itis prolapsing into the left ventricle and causingmitral incompetence, as in Patient 2. Passage ofthe myxoma from left atrium to left ventriclewas not shown in the angiograms presented byGoldberg et al. (1952) or by Steinberg et al. (1953).A further interesting feature was failure to fill

the right lower lobe pulmonary veins in twopatients (1 and 4), probably because of obstructionby thrombus. We thought that the same veinswere obstructed in Patient 3, who also had signsof infarction in the right lower lobe.We do not know whether obstruction to right

lower lobe pulmonary veins is a feature peculiarto myxoma, but it is possible that the tumourobstructs drainage to this lobe. The finding inthree of our four cases may well be significant,and should be considered as suspicious of a leftatrial myxoma if other features also suggest thecondition.CARDIAC CATHETERIZATION (Table I).-There

were no diagnostic features; the low cardiacoutput, high pulmonary vascular resistance, andpulmonary arterial venous hypertension werecharacteristic of severe mitral valve disease.These findings correlated well with the radio-logical signs. They are of value only in localizingthe site of the disorder of the pulmonarycirculation to the venous side of the pulmonaryvascular bed, and thus suggesting obstruction atatrio-ventricular level.

RADIOACTIVE GAS STUDIES.-Examination withradioactive carbon dioxide labelled with oxygen-15(C'502) in two patients showed changes identicalwith those found in severe mitral stenosis, therebeing diminished perfusion in the lower portionsof the lungs as compared with the upper portions(Dollery and West, 1960).

In both cases, these findings correlated with theradiological appearances of the pulmonary arteries,which were also closely similar to those foundin severe mitral valve disease (Doyle, Goodwin,Harrison, and Steiner, 1957). Our studies affordedfurther information that any lesion which increasesleft atrial pressure causes constriction of thevessels to the lower lobes of the lungs.DISORDER OF PLASMA PROTEINS.-Although

abnormal globulins have previously been describedin myxoma (Skanse et al., 1959; Evans, 1959;MacGregor and Cullen, 1959; and Frankenfeldet al., 1960) sufficient attention has not been paidto this disorder in diagnosis in the past.

All our four patients had increased serumgamma globulins and altered albumin-globulin

ratios when studied by paper electrophoresis.The serum albumin was always above 2 g. %(Fig. 1). From time to time these protein patternsvaried considerably quantitatively but remainedqualitatively similar, the excessive globulin usuallybeing in the gamma position. They returnedtowards normal after operation (Fig. 6). InPatient 3 the proteins were initially normal,showing that more than one estimation may berequired to detect the abnormalities.The reason for the abnormal proteins is

unknown, but we think they are related to thefever, anaemia, raised sedimentation rate, malaise,and loss of weight from which these patientssuffered. These features could be explained bya general poisoning of the body tissues by themyxoma, probably by release into the circulationof some abnormal substance; or, less likely, byrepeated tiny emboli. The myxoma itself mayform excessive or unusual globulin, but there wasno qualitative abnormality in the serum gammaglobulins, and autoantibodies have not beendetected in the patients' blood. Histochemicalstudies by our colleague, Dr. Everson Pearse, arein progress.

All patients had severe pulmonary arterial andvenous hypertension, and this may haxe been insome way connected with the serum proteindisorder. The return of the proteins to normalafter removal of the myxoma established beyondquestion that the tumour was the cause of theprotein abnormality.ANAEMIA AND RAISED E.S.R.-All patients had

at some time a raised erythrocyte sedimentationrate and variable degrees of anaemia, usually 10to 12 g. % of haemoglobin. The anaemia wasnonspecific in type, with slight reduction in meancorpuscular haemoglobin concentration and aniso-cytosis and microcytosis suggesting iron deficiencyor a toxic depression of the bone marrow. Sternalmarrow studies in our first patient did not revealany characteristic abnormality. The white bloodcell counts were unremarkable.

DIFFERENTIAL DIAGNOSIS FROM SUBACUTE INFEC-TIVE ENDOCARDITIS.-The presence of clubbingincreases the similarity between myxoma andbacterial endocarditis. Changing "mitral mur-murs," emboli, loss of weight, anaemia, fever,sweating, raised erythrocyte sedimentation rate,clubbing, and anaemia are features common toboth diseases, and on first examination thedifferential diagnosis may be impossible. Theabsence of splenomegaly in our cases of myxoma,and its frequency in infective endocarditis, mayprovide a useful clue, as may the failure of the

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patient with a myxoma to improve with fullchemotherapy for suspected bacterial endocarditis.Repeatedly negative blood cultures do not providea certain differentiation, for these are not alwayspositive in infective endocarditis (Dormer, 1958;Goodwin, 1960) (Table V).

TABLE VDIFFERENTIAL DIAGNOSIS OF BACTERIAL ENDOCARDI-

TIS AND LEFT ATRIAL MYXOMA

Clinical Features

History of rheumatic feverRapid progressionSyncopeSystemic embolism with sinus rhSinus rhythmAtrial fibrillationChanging murmursFeverLoss of weightAnaemiaHigh E.S.R.HyperglobulinaemiaSolenomegalyBlood culturesResponse to antibioticsOther valve lesions

Subacute Bacterial LeftEndocarditis on AtrialMitral Valve Myxoma

c. 50

+

+

(+)

I-

+ usually+ ,,

+ often

0

+

(±)

l-L

Abnormal serum proteins may also occur ininfective endocarditis (Flynn, 1954) and in severeand prolonged congestive heart failure.We accordingly examined all our proven cases

of infective endocarditis with positive bloodcultures. Unfortunately, in only six had theserum proteins been estimated when the diagnosishad been confirmed by positive blood cultures.Table VI shows that the serum proteins weresignificantly altered in only three patients, andexamination of the electrophoretic patterns inmyxoma and bacterial endocarditis by ourcolleague, Dr. I. D. P. Wootton, did not reveal anyqualitative difference between the two conditions.

TABLE VISERUM PROTEINS IN SIX PATIENTS WITH INFECTI VE

ENDOCARDITIS AND POSITIVE BLOOD CULTURES

Patient Albumin Globulin(g-%) (g-%)

ABC

DEF

2-03-63.52-130

2-853-6

3-73.93-13 04-12-854-1

We do not believe that the study of the serumproteins contributes to the differential diagnosisof the two diseases, except in so far as normalproteins do not exclude bacterial endocarditis,whereas repeatedly normal proteins would appearto be unlikely in a patient with myxoma.

The differential diagnosis from bacterial endo-carditis applies only when evidence of valvulardisease other than mitral stenosis or incompetenceis absent. The finding of definite aortic valvedisease makes a myxoma improbable.SURGICAL TECHNIQUE.-Successful removal of

left atrial myxoma has been achieved on a numberof occasions, and Differding, Gardner, and Roe(1961) in their review quote at least 43 cases.Many authors report only one case, althoughCooley, Morris, and Attar (1959) mention three,and Differding et al. (1961) two successfuloperations using cardio-pulmonary bypass.Our three patients were operated on using

extracorporeal circulation with the Melrose-N.E.P.pump-oxygenator under the supervision of Dr.D. G. Melrose. The flow rate was 2.4 1. persquare metre of surface area.The left atrium was approached through the

right atrium and inter-atrial septum. Thisapproach was first described by Brock (1956),and we have found it gives direct access to thetumour with an excellent view of its pedicle,thus permitting easy delivery and minimizingfragmentation of the tumour (Fig. 11).

It seems logical to adopt a surgical approachwhich allows ready identification and completeexcision of the tumour pedicle and the relatedpart of the inter-atrial septum.

Gentle delivery of this most friable tumour isessential especially when it is impacted in the ringof the mitral valve. The importance of aorticocclusion during manipulation of the tumour andcareful inspection of the left ventricle and leftatrium for tumour fragments is emphasized.Thorough lavage of the interior of the heart beforeclosure is important. From the time that thetumour is exposed, use of the normal intracardiacsuction apparatus is discontinued and a specialsucker is used, the contents of which are discarded.VASCULAR PRESSURES AFTER REMOVAL OF THE

MYXOMA.-In each patient there was a fall inleft atrial pressure immediately after removal ofthe tumour, that in the third patient being themost dramatic, the systolic pressure falling to onethird of its pre-operative level. As would beexpected, the pulmonary artery pressure fell lessdramatically, and in Patient 4 there was nosignificant change. The rise in systemic arterialpressure in Patients 2 and 4 is consistent with afall in total pulmonary vascular resistance anda rise in cardiac output. The slight fall inpulmonary arterial pressures denies any significantimmediate pulmonary vasodilatation and fall inarteriolar resistance, and is consistent with the

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persistence of accentuation of pulmonary valveclosure, indicating residual pulmonary hyper-tension. It is probable that pulmonary vasculardisorder, as after mitral valvotomy, will take sometime to resolve and that the pulmonary arteriolarresistance will fall slowly.PATHOLOGY.- All four tumours were sur-

prisingly consistent in their pathological features.They all had narrow, rather fibrotic pedicles, andthree bore the indentation of the mitral valvering which distorted the shape and made it possibleto delineate an atrial and ventricular portion.They were similar also in that their point ofattachment was in each instance to the posterioror postero-inferior margin of the fossa ovalis.The external appearance was that of a lobulatedglistening mass with fronds or rounded projectionsof softer gelatinous, pale yellowish-pink material,which was rather friable, and scattered darkerareas of haemorrhage. The overall consistencywas rubbery, being somewhat firmer centrally thansuperficially (Fig. 5).Each tumour was sectioned through the pedicle

and longest length in order to see the dispositionof the histological elements. The pedicle was firmand often fibrotic, and in it ran several thick-walled vessels which soon became small capillarychannels. The fibrosis extended in frond-likefashion into the main mass, and in this regionthere were a variable number of haemosiderin-containing macrophages and free pigment. Thiswas most evident in Patient 1.The main tumour mass consisted of a pale,

myxomatous stroma, scattered in which were thesomewhat embryonic cells, stellate in shape andwith cytoplasmic processes, usually singly or insmall groups forming syncytia. A few smallcapillaries were present, and haemorrhage aroundthem was not uncommon. Fine strands of elastictissue were also present, but mainly in the regionof the blood vessels in the pedicle. The endotheliallining of the atrium was continuous over the wholeof the surface of the tumour, and this surfacelayer of cells was very similar to the cellscomprising the main mass. Some cells weremultinucleate, but there were no mitoses. Theunderlying atrial wall was normal (Fig. 3).

DISCUSSIONIt is apparent from our four patients, and from

the additional patient described from this hospitalby MacGregor and Cullen in 1959, that thecombination of signs of pulmonary venous andarterial hypertension with apical murmurs of achanging character and signs of a general systemic

disorder with fever, anaemia, or abnormal serumproteins and raised erythrocyte sedimentation rateis highly suggestive of a left atrial myxoma.Three comprehensive retrospective reviews of

atrial myxoma have recently appeared, dealingmainly with cases diagnosed for the first time atoperation or at necropsy (Campeau and David,1960; Aldridge and Greenwood, 1960; Differdinget al., 1961). Campeau and David reported 65myxomas (57 in the left atrium) collected over aperiod from January, 1954, to January, 1959.Aldridge and Greenwood published an analysisof 32 cases of left atrial myxoma reported inthe literature, and added three of their own.Presumably some of the same cases have beenreported in both these papers. Campeau andDavid reported that eight of their cases (18%)had resembled bacterial endocarditis with loss ofweight, fever, petechiae, and raised sedimentationrate, but no splenomegaly and negative bloodcultures. Differding et al. stressed that embolicphenomena and fever might suggest bacterialendocarditis. Aldridge and Greenwood, in listingthe manifestations in their cases, did notmention any features which suggested generalsystemic disease or infection. The commonestsymptoms were the usually accepted ones ofshortness of breath, right-sided heart failure, pul-monary oedema, paroxysmal nocturnal dyspnoea,and systemic embolism. Syncope was compara-tively uncommon and occurred in only four ofthe cases. Aldridge and Greenwood, however,stated that blood cultures were carried out in tencases and were negative, but the reason for takingthe cultures was not clear from the original casereports.

Despite reports in the literature of abnormalserum proteins in some patients, this feature hasnot previously been stressed. Serum proteinestimations have been reported in ten patients withmyxoma (Martin, 1953; Morton, 1954; Davis andAndrus, 1954; Lekisch, 1957; Skanse et al., 1959;Evans, 1959; MacGregor and Cullen, 1959;Frankenfeld et al., 1960; Aldridge and Green-wood, 1960), and in five of these there hasbeen an abnormal albumin-globulin ratio andhyperglobulinaemia. The patient reported byMacGregor and Cullen (1959) had macroglobulin-aemia. Fever is mentioned as occurring in 14of 65 patients reported by Campeau and David(1960).The importance of signs of an infective or

general systemic disorder in arriving at an accuratediagnosis has already been stressed. The otherfeatures of the disease, such as changing mitral

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CLINICAL FEATURES OF LEFT A TRIAL MYXOMA

murmurs, third heart sound, and opening snap ina small proportion of cases, are well recognizedand do not need further emphasis. The shorthistory of the disease and rapid onset of severepulmonary hypertension and heart failure areemphasized by Aldridge and Greenwood (1960)and are borne out by our patients. Data obtainedat cardiac catheterization revealed evidence ofpulmonary arterial and venous hypertensionresembling mitral valve disease of a seriousdegree. We are not aware of any previousmention of a widely split first heart sound, andbelieve that this may possibly be of some valuein diagnosis. We do not know whether occlusionof the right lower lobe pulmonary veins withconsequent pulmonary infarction in the rightlower lobe is of diagnostic significance, but itsoccurrence in three of our four patients leads usto regard it as a possible clue to left atrial myxomain the future.The features of myxoma may indeed be protean,

for ischaemic heart disease may occur in additionto pulmonary hypertension, systemic embolism,and general systemic disorder. Harvey (1957)reported cardiac infarction due to coronaryembolism, and Dr. D. H. Davies, of Bristol,has shown us two patients with myxoma andcoronary embolism. Myxoma should therefore beconsidered in the differential diagnosis of a patientwith unusual features of cardiac ischaemia.The definitive diagnosis of myxoma is made by

adequate selective angiocardiography. We believethat the lobulated nature of the filling defect ischaracteristic. Its passage between atrium andventricle is also important and has not previouslybeen stressed.

Accurate diagnosis is clearly of great import-ance, for the record of successful treatment isnot good. Only 13 of 38 patients operated uponfor atrial myxoma were diagnosed correctly beforean operation for embolectomy or valvotomy(Differding et al., 1961). Campeau and David(1960) reported that of 45 left atrial myxomasonly four were suspected clinically, and threeconfirmed by angiocardiography, while 16 werediscovered accidentally during surgery for mitralstenosis, and 22 were diagnosed at necropsy.

Previous reports, and the progress so far of ourthree patients from whom the tumour has beensuccessfully removed, suggest that this conditionis completely curable when treated in the correctfashion. Untreated it leads inexorably to a fataloutcome.Of a total of 66 patients with left atrial myxoma

reported by Gleason (1955) and by Campeau and

David (1960), 13 were suspected of havinginfective endocarditis, and the differential diagnosisbetween this condition and myxoma is thereforeof real importance.We consider that the condition should be

suspected in any patient without a history ofrheumatic fever and without evidence of othervalve disease, who presents a rapid downhill coursewith loss of weight, signs of general systemicdisease, abnormal serum proteins, fever, and signsof mitral valve obstruction with pulmonary hyper-tension. As with mitral valve disease, myxomaappears to be more common in women; of the35 cases reported by Aldridge and Greenwood(1960), 26 were women and only nine were men.This agrees with our own finding of three womenand one man.Absence of a history of rheumatic fever is of

little value in diagnosis, for approximately 50%of patients with mitral stenosis have no historyof rheumatic fever, while a history of rheumaticfever has been reported in a patient with myxoma(Belcher, 1958).Myxoma and mitral valve disease may co-exist

(Marions and Odman, 1957; Aldridge andGreenwood, 1960), while myxoma developing ina patient who had previously had a valvotomyfor mitral stenosis has been documented byDeshmukh, Nichols, and Goldberg (1959).

CONCLUSIONSAs a result of our experience, we believe that

left atrial myxoma may now readily be suspectedclinically, proven radiologically, and cured sur-gically. Clinical suspicion, however, should ariseless from embolic and haemodynamic featuresthan from signs and symptoms suggesting general-ized inflammatory disease in a patient withpulmonary hypertension, heart failure, or signssuggesting mitral valve disease.

SUMMARYFour patients with myxoma of the left atrium

are described. The diagnosis was made correctlyin all four without the aid of surgery or necropsy,and in the three who came to surgery the tumourwas successfully removed.

All patients presented with rapidly progressivecardiac illness, severe pulmonary hypertension,and signs suggesting mitral valve disease. Theyall showed abnormalities in the serum proteins,consisting of elevation of the globulin factors,usually in the gamma position. Bacterial endo-carditis was closely simulated in two patients, andsubacute rheumatic fever in one.

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The clinical picture, results of special investi-gations, diagnosis, and surgical treatment are

described. Special emphasis, hitherto not reported,has been paid to the serum protein disorder in

diagnosis, and the differentiation from bacterialendocarditis is discussed.

We are grateful to Mr. W. P. Cleland and to Dr.R. S. Bruce Pearson for kindly referring Patient 4 andto Drs. D. H. Davies and D. W. Barritt for Patient 3.

We are also indebted to Mr. Cleland and to Mr. L. L.Bromley for allowing us to quote their operationnotes. Dr. Arthur Hollman kindly performed the leftventricular angiogram in Patient 2 and took theoperation photograph (Fig. 11).

REFERENCESAldridge, H. E., and Greenwood, W. F. (1960). Brit. Heart J., 22,

189.

Belcher, J. R. (1958). Brit. J. Tubere., 52, 62.Brock, R. C. (1956). Guy's Hosp. Rep., 105, 382.Campeau, L., and David. P. (1960). Canad. med. Ass. J., 82, 586.Cooley, D. A., Morris, G. C., and Attar, S. (1959). A.M.A. Arch.

Surg.. 78, 410.Davis, F. W., and Andrus, E. C. (1954). New Engl. J. Med.,251, 297.Deshmukh, M., Nichols, H. T., and Goldberg, H. (1959). Amer.

Heart J., 58, 623.Differding, J. T., Gardner, R. E., and Roe, B. B. (1961). Circulation,

23, 929.

Dollery, C. T., and West, J. B. (1960). Circulation Res.. 8, 765.Dormer, A. E. (1958). Brit. med. J., 1, 63.Doyle, A. E., Goodwin, J. F., Harrison, C. V., and Steiner, R. E.

(1957). Brit. Heart J., 19, 353.Evans, W. (1959). Ibid., 21, 197.Flynn, F. V. (1954). Proc. roy. Soc. Med., 47, 827.Frankenfeld, R. H., Waters, C. H., and Steiner, R. C. (1960). Ani,v.

intern. Med., 53, 827.Gleason, I. 0. (1955). Cancer, 8, 839.Goldberg, H. P., Glenn, F., Dotter, C. T., and Steinberg, 1. (1952).

Circulation, 6, 762.Goodwin, J. F. (1960). Proc. rov. Soc. Med., 53, 556.Harvey, J. C. (1957). Ann. intern. Med., 47, 1067.Leach, W. B. ( 1947). Arch. Path. (Chicago), 44, 198.Lekisch, J. (1957). Ann. intern. Med., 46, 982.MacGregor, G. A.- and Cullen, R. A. (1959). B-it. med. J., 2, 991.Marions. 0., and Odman, P. (1957). Acta radiol. (Stockh.), 47, 461.Martin, B. F. (1953). Ann. intern. Med., 38, 325.Morton, E. V. B. (1954). Edinb. m?ed. J., 61, 227.Prichard, R. W. (1951). A.MtA.A. Arch. Path.. 51, 98.Skanse, B.. Berg, N. O., and Westfelt, L. (1959). Acta medt. scanid..

164, 321.Steinberg, I., Dotter, C. T., and Glenn. F. (1953). Dis. Chest, 24, 509.

ADDENDUM

Since writing this paper we have become awareof a report of hypertrophic osteoarthropathy ina patient with a primary rhabdomyosarcoma ofthe heart (Pascuzzi, C. A., Parkin, T. W., Bruwer,A. J., and Edwards, J. E., Proc. Mayo Clin., 1957,32, 30).

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