Postgraduate Medical Journal (December 1972) 48, 722-731.

Clinical demonstrations

PROFESSOR J. F. GOODWIN

WE present the case histories and documentationon a number of patients who illustrate certainaspects of the cardiomyopathies, starting with threepatients who demonstrate some of the features andproblems of congestive cardiomyopathy. Case 1 is aso-called 'index' case with the clear characteristics ofcongestive cardiomyopathy. Case 2 confused theissue by presenting with angina and thereforesimulated ischaemic heart disease, an important anddifficult problem. Case 3 did the reverse; he presentedwith heart failure without a definite episode ofcardiac infarction but was found to have severecoronary artery disease and thus his myocardialfailure was due to this and not to cardiomyopathy.Then three patients (Cases 4, 5 and 6) with hyper-trophic cardiomyopathy will be presented whoillustrate some of the familial aspects, some of thediagnostic difficulties and the importance of histo-logical evidence. Finally, we shall discuss somepatients who demonstrate certain forms of secondarycardiomyopathies. These will be three patients withskeletal muscular dystrophy (Cases 7, 8 and 9) anda patient with acromegaly (Case 10) all of whompresented with, or came to our notice with severemyocardial disease and heart failure.

Case 1 (Presented by Dr Geoffrey Lane)A 42-year-old male architect whose only past

history was mild asthma in childhood and whoremained perfectly well and fit up until December1970. He then developed nausea and diarrhoeafollowed by shortness of breath, tightness in thechest and wheezing when walking. Effort dyspnoeapersisted and in January 1971 he developed paroxy-smal nocturnal dyspnoea. He was admitted to hospitalat this time with signs of bilateral heart failure andimproved on treatment with digoxin and diuretictherapy. Tachycardia persisted however, and car-diomegaly on X-ray was unchanged. Three monthslater he developed further nausea, diarrhoea anddyspnoea and was again admitted to hospital, and2 weeks later was transferred to HammersmithHospital (April 1971). His symptoms were dyspnoeaon minimal effort, orthopnoea, paroxysmal nocturnaldyspnoea; he also had intermittent colicky right iliacfossa pain, a symptom which he had had inter-mittently over a period of fifteen years.

On examination he was a chronically ill man withgross congestive cardiac failure. Blood pressure was100/80 mmHg, pulse 120/mm with frequent ectopics,jugular venous pressure markedly elevated with veryprominent 'a' wave. There was an accentuatedpulmonary component of the second sound and athird heart sound. The apical impulse was diffuseand there was a left parasternal impulse. He hadmarked oedema, basal crepitations and an en-larged liver.

Investigations. His ECG showed sinus tachycardia,a poor progression of the R wave from V1 to V4 andrepolarization changes, with an occasional ven-tricular ectopic beat. The chest X-ray showed grosscardiomegaly and prominent upper zone vessels.The haemoglobin was 16-3 g/100ml, WBC 6600cells/cm3, PBI 5-6,g/100 ml,VMA 8 tzg/mgcreatinine;his serum albumin was 1-8 g/100 ml. On admis-sion he showed quite severe hypokalaemic alkalosis;potassium 2-4 mEq/l.Course. Congestive cardiomyopathy was considered

as the most likely diagnosis and treatment wascontinued with digoxin and frusemide 160 mg/daywith potassium supplementation. However, hiscourse was complicated first by the development ofacute tubular necrosis with oliguria and hypo-natraemia (urea 129 mg/100 ml, Na 117, K 6-9 andHCO3 11 mEq/l) requiring therapy initially in theform of hypertonic saline and glucagon, and thenfrusemide in large doses. With this combination oftherapy he showed transient improvement but thendeveloped further complications; atrial fibrillation(from which time he was put on anticoagulants) andlater two episodes of staphylococcal septicaemia.He steadily became more jaundiced and he died incongestive cardiac failure approximately 6 monthsafter the first onset of symptoms attributable tocardiac disease.

Necropsy findings (Dr E. J. G. Olsen)(1) Mural thrombus in a dilated and hyper-

trophied heart. Post-mortem coronary arteriographyshowed normal coronary arteries.

(2) Pulmonary emboli from venous thrombosisin legs.

(3) Early renal papillary necrosis.(4) Two gastric ulcers; islet cell adenoma of

pancreas.

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Professor GoodwinThis is a distressingly common, though by no

means invariable, course for congestive cardio-myopathy; a 6 months' downhill progression. Somefactor or factors unknown had destroyed thecontractile power of the myocardium. Virus studiesin this patient, and in other patients, have beennegative in our experience, possibly because we seethese patients late in the condition. One is left, evenafter detailed pathology, with a huge question markas to the causation.

DiscussionDR FORSTER (Zurich): At necropsy this patient showed

an islet cell adenoma of the pancreas and gastric ulcersas well as diarrhoea. Could he be a case of Zollinger-Ellison syndrome with cardiomyopathy? Do you thinkthat some disturbance of carbohydrate metabolism couldbe responsible for this cardiomyopathy and have youseen a similar case previously?

PROFESSOR JOHN GOODWIN: No, we have not seen thiscombination before but I suppose it is feasible.

Case 2 (Presented by Dr C. M. Oakley)The next patient, aged 55, worked as a packer.

He presented earlier this year with a 4-year historyof epigastric and retrosternal pain which went intothe left arm on exertion. The pain sounded typicalof ischaemic cardiac pain and was diagnosed asangina. In December 1970 he went into left vent-ricular failure for the first time and shortly after-wards was admitted to hospital (January 1971).A diagnosis of cardiac infarction leading to leftventricular failure was made and while in hospitalhe had a cerebral embolus whose effects were transientIn March 1971, he was re-admitted to hospital withchest pain, again in cardiac failure. On this occasionhe was very ill and went into ventricular fibrillationbut recovered from these episodes. In May 1971 hewas referred to Hammersmith Hospital with adiagnosis of left ventricular aneurysm.On examination he was a thin, small, quiet man

with arcus senilis. Blood pressure 95/60 mmHg;sinus rhythm with slight pulsus alternans. The leftventricle was obviously enlarged with a sustainedimpulse and a palpable gallop; apical fourth andthird sounds present. The chest X-ray showed alarge dilated left ventricle. The ECG showedcomplete left bundle branch block and atrial para-systole. Serum cholesterol 221 mg/100 ml, serumtriglyceride (fasting) 68 mg/100 ml, haemoglobin anduric acid levels normal. Cardiac catheterization re-vealed a very low cardiac output, a high leftventricular end-diastolic pressure and moderatepulmonary hypertension. Selective coronary angio-graphy and a left ventricular angiogram were carriedout. The left ventricle was very large and beat withdecreased vigour; there was no evidence of a

ventricular aneurysm and no thrombus was seen inthe cavity. The coronary arteries were normal.For left ventricular failure to be explained by

coronary artery disease, we expect to see majorocclusive disease affecting at least two vessels, Thusdespite the history of angina for 4 years and thestriking physical signs suggesting aneurysm, thispatient has generalized left ventricular failure ofundetermined (but non-coronary) cause, i.e. con-gestive cardiomyopathy. Some clinical clues pointingaway from the diagnosis of ischaemic heart diseasewere the absence of major or minor coronary 'risk'factors and the complete left bundle branch blockon the ECG. The latter admittedly obscures thediagnostic changes of cardiac infarction but a pre-sentation in left ventricular failure with left bundlebranch block more often means cardiomyopathythan coronary disease.

DiscussionQUESTION. Why do you think this patient has had

angina or pseudo-angina?DR CELIA OAKLEY: I don't know why he has angina

but I can suggest some reasons why he should haveangina. I think it is not pseudo-angina, but real anginaand it is not uncommon in congestive cardiomyopathy.These patients must have a greatly increased myocardialmetabolic demand. Firstly, they have an increased cavitysize and therefore for any pressure generated, the walltension must be greater than usual; wall tension is oneof the main factors concerned with metabolic demands.Secondly, the left ventricular muscle mass is greater thannormal. Thirdly, patients with congestive cardiomyo-pathy maintain their minute output by means of tachy-cardia, and metabolic demand is directly related tocardiac rate. Finally, this high rate will also reducediastolic filling time so that myocardial blood flow maybe curtailed. These are the several reasons why he mighthave angina!PROFESSOR JOHN GOODWIN: Do you think that the

most important factor is the increased ventricular sizewith increased wall tension and increased oxygendemand?DR CELIA OAKLEY: I think it is increased oxygen

demand from a number of different factors, all ofimportance.DR WALLACE BRIGDEN: How do patients with cardio-

myopathy and angina respond to trinitrin?PROFESSOR JOHN GOODWIN: I am not sure I know the

answer to that. I suppose they usually respond becausethe effect of trinitrin is to reduce cardiac work.

Case 3 (Presented by Dr Michael Dean)This patient was a 49-year-old man (a public

relations officer) who illustrates the way in whichischaemic heart disease can mimic the picture ofcongestive cardiomyopathy. In 1966 he was foundto have mild diabetes which was adequately con-trolled by diet and in 1968 a chest X-ray revealedmild cardiomegaly. Over a period of 3 weeks inearly 1971 he developed increasing breathlessness

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on exertion and paroxysmal nocturnal dyspnoea,and was promptly admitted to hospital. He wasnoted to have a tachycardia, elevation of jugularvenous pressure, basal crepitations and an atrialgallop. Treatment with digoxin and diuretics pro-duced rapid improvement and he was referred toHammersmith Hospital for further evaluation witha tentative diagnosis of congestive cardiomyopathy.It is of interest that at no time was there any chestpain to suggest angina pectoris or myocardialinfarction. He smoked about thirty cigarettes per day,and there was a fairly heavy intake of alcohol.On admission he was virtually symptom-free but

there was clinical evidence of left ventricular en-largement and both third and fourth heart soundswere audible. The liver was somewhat enlarged,possibly as a result of his rather heavy alcohol intake.Investigations revealed slight impairment of glucosetolerance and there was elevation of both fastingcholesterol and triglyceride levels; cholesterol 350 mg100 ml and triglyceride 290 mg/100 ml. Chest X-rayshowed moderate cardiac enlargement with noevidence of cardiac failure. The electrocardiogramrevealed sinus rhythm with Q waves in leads I,aVL, and across the left praecordial leads. Theappearance was compatible with an old anterolateralinfarction.

Cardiac catheterization with coronary angiographywas performed to help clarify the diagnosis, whichwas felt to be either ischaemic heart disease, assuggested by the electrocardiogram, or congestivecardiomyopathy. The pulmonary artery pressure waselevated to 62/28 mmHg and the mean pulmonarycapillary wedge pressure was 12mmHg. Leftventricular pressure was 115/5-17 mmHg and theleft ventricular end-diastolic pressure rose to40 mmHg during a brief episode of junctionaltachycardia. The left ventriculogram showed a largeventricular cavity with an akinetic area at thecardiac apex and relatively good contraction of thebasal portions of the ventricle. The coronaryarteriograms revealed complete obstruction of theleft anterior descending coronary artery. Both thecircumflex branch of the left coronary artery andthe right coronary artery were patent but hadseveral minor irregularities of the lumen suggestingthe presence of atheroma. There was some collateralcirculation from the right coronary artery to theleft side.

Thus, the clinical presentation of cardiac failurein this patient seems to be on the basis of ischaemicheart disease. It is of interest that there were nosymptoms to point to this diagnosis and the mainpiece of evidence in favour of this was the electro-cardiogram. In addition there were present severalof the known 'risk factors'-notably mild diabetes,elevated lipids, and cigarette smoking.

DiscussionDR F. HAAGEN (Utrecht): Were all your patients

seriously interrogated regarding excessive alcohol intake?PROFESSOR JOHN GOODWIN: This is an important

question and I am glad that it was asked. In our exper-ience, alcohol does not seem to be an important factor,although this might depend on what is regarded as ahigh alcohol intake. The patients we see have levels ofalcohol intake which are difficult to evaluate. My personalbelief is that alcohol in many patients is no more thanone of the factors but it is seldom the major cause. I thinkthere is a wide variation in individual tolerance, as withalcoholic cirrhosis. We do not find alcohol an importantfactor in our patients with congestive cardiomyopathy.DR WALLACE BRIGDEN: I have no doubt that alcohol

is in some situations, in some people and in some places,an outstandingly important cause of primary disease ofthe heart. The evidence for this is now overwhelmingand comes from clinical, experimental and pathologicalstudies and in the specific findings of electron microscopy.DR E. G. J. OLSEN: Personally, I am unable to distin-

guish at histological or histochemical level, as to whetheror not a patient has been subjected to a tremendousamount of alcohol. This comment extends to the electronmicroscopic level as well.

Familial hypertrophic cardiomyopathy (Presented byDr Celia Oakley)Case 4.A female, 58 years old in 1971, was first seen at

Hammersmith Hospital in 1958 (aet 45 years). Fivemonth before being seen she had developed atrialfibrillation and was treated with digitalis. A monthlater she developed a left renal embolus and anothermonth later, a saddle embolus. When referred toHammersmith Hospital she had effort dyspnoea,palpitations and a transient right hemiplegia.The cardiovascular findings included atrial fibril-

lation, an elevated JVP, and an enlarged tenderpulsatile liver. The heart was moderately enlarged onX-ray but there were no murmurs and no addedsounds. She developed a left hemiplegia while inhospital. There has been little change clinicallyduring the past 13 years. Occasionally she returns tosinus rhythm and haemodynamic studies in 1959and 1966 showed an increasing left atrial andpulmonary artery pressure with a small reductionin cardiac output. The left ventricular angiogramshowed the features ofhypertrophic cardiomyopathy.The left ventricular cavity was deformed but notdilated. The ventricular wall was grossly thickenedbut it contracted well. This patient had clinicalfeatures suggesting pump failure (congestive cardio-myopathy) with haemodynamic and angiographicabnormalities of compliance failure (hypertrophiccardiomyopathy).As this patient recovered she said that she had

lost a son at the age of 15 years. He had diedsuddenly while walking along the street and necropsy

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had revealed 'heart disease'. It was not possible toobtain the report of the coroner's necropsy. Shealso said that her daughter had a heart murmur.

Case 5Her daughter, was investigated at the age of 15.

She was asymptomatic but a murmur had beennoted at a school medical examination some yearsearlier. She was in sinus rhythm and there was noevidence of cardiac failure; the heart was notenlarged, although the left ventricular impulse wasprominent and there was a palpable atrial beat atthe apex. In addition there was an apical systolicmurmur and a third sound or short mitral diastolicmurmur.The girl had all the clinical features, haemo-

dynamic and angiographic findings of hypertrophiccardiomyopathy (HOCM) with mild obstruction toleft ventricular outflow.CommentAt the time that we first saw these patients we

were only beginning to realize that patients withHOCM need not necessarily have murmurs oroutflow tract obstruction and that they mightdevelop or present with congestive heart failure.The features of this family with hypertrophicobstructive cardiomyopathy include sudden death inone member at the age of 15 years and a murmurdetected in another at 15 years who is now in hertwenties, married and has had a child. Her diseasehas not apparently progressed and this is typical ofHOCM. In the mother, the heart disease was onlyrecognized in her late forties when she had alreadyhad her family and she presented in congestivecardiac failure.The mother's illness drew attention to the

daughter's cardiac abnormality which otherwisemight have remained undetected until she in herturn presented with complications of the disease inlater life. This mother and daughter also underlinethe usual under-diagnosis of this disorder in child-hood. The signs are often unspectacular andattributed to innocent causes so that the majorityof children who are referred to us have quiteatypically severe forms of the disorder.

Case 6A housewife, now aged 36 years, was unaware of

any problem until the birth of her third child (1966)when her abdomen and ankles remained swollenafter delivery and amenorrhoea persisted. In 1970she had her varicose veins stripped but withoutimprovement and a laparotomy was performed forthe suspected diagnosis of ovarian carcinoma. A liverbiopsy taken at that time suggested cardiac failure, andshe was referred to Hammersmith Hospital.

In the past she had been treated for asthma in

1962 and for pulmonary tuberculosis in 1967. Therewas no family history of heart disease. She had threechildren aged 2, 9 and 13 years. For about 1 yearshe had been short of breath, with blueness of theface and hands on stooping.On examination she was very thin with hepa-

tomegaly and gross ascites, peripheral cyanosis, asmall volume pulse in sinus rhythm with no arterialparadox; she was obviously in a low cardiac outputstate. Her venous pressure was high in the neck witha dominant 'y' descent. The cardiac impulse showeda marked right ventricular diastolic thrust, such asis described in constrictive pericarditis. There was noleft ventricular impulse, a loud third heart soundgallop and an intermittent tricuspid systolic murmurThe chest X-ray showed a moderately enlarged

heart. Earlier films taken during her anti-tuberculoustherapy showed slight cardiac enlargement in 1969.The ECG showed definite bilateral atrial enlarge-ment. The echocardiogram suggested a smallpericardial effusion and showed a rapid diastolicclosure slope quite unlike HOCM. The differentialdiagnosis at this stage was between constrictivepericarditis and HOCM.

Cardiac catheterization. The mean right atrialpressure (16 mmHg) was identical with the indirectleft atrial pressure, which is typical of constrictivepericarditis but the left ventricular end-diastolicpressure (LVEDP) (26 mmHg) was much higher thanthe right ventricular end-diastolic pressure due to agrossly augmented 'a' wave. There was very littlepulmonary hypertension; a high LVEDP, an aug-mented 'a' wave and significant pulmonary hyper-tension always weigh heavily against constrictivepericarditis and are more suggestive of cardio-myopathy. There was no gradient between the leftventricle and aorta after amylnitrite. Cine-angio-graphy showed slight systolic mitral incompetence,normal left ventricular activity, no cavity dilatationand considerable thickening of the left ventricularwall whose cavity was smooth and featurelesswithout papillary muscle indentations.The patient thus had no evidence of left ventricular

systolic dysfunction with a raised filling pressure andcongestive failure secondary to this. A decision hadto be made as to whether the left ventricular diastolicdysfunction arose from pericardial restriction ormyocardial disease. Although there were severalfeatures against a diagnosis of constrictive peri-carditis, it was considered that it should be excludedand a thoracotomy was performed. The pericardiumwas normal, the left ventricle was small and grosslythickened and the left atrium was tense. Biopsieswere taken from all the cardiac chambers and therewere some features in the left ventricular biopsywhich were suggestive of HOCM with hypertrophyotherwise unexplained.

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DiscussionDR OLSEN: On conventional histological examination

one can immediately see that the regular arrangementof the myocardial fibres is dissociated and that most ofthe fibres show considerable hypertrophy. In hyper-trophy resulting from stenosis or hypertension, the fibresmeasure 15-20 ^m in diameter; in hypertrophic obstruc-tive cardiomyopathy the fibres are larger, from 60-90 g.m.The nuclei are abnormal in shape with a perinuclear haloand there are widespread dystrophic changes within themyocardial fibres. There is also an increase in fibroustissue between the myocardial fibres. At a histologicallevel, these findings indicate hypertrophic cardiomyo-pathy and the only value of histochemical examinationis to demonstrate the considerable glycogen accumulationin the perinuclear area.On electron microscopy the individual myofibre com-

ponents are dissociated and there is a striking cross-overfrom one fibre to another. This appearance is not patho-gnomonic, but it is seen more frequently and to a greaterdegree in HOCM. On cross-section, the mitochondriaare dilated and the cristal arrangement is disrupted, withlarge vacuoles appearing within the cristae. The nuclearmembrane is prominent and crenellated.DR C. OAKLEY: In this patient the diagnosis before

biopsy had to be reached by exclusion. She had leftventricular hypertrophy with diastolic compliance failureand therefore she had HOCM. Dr Olsen did not knowthe clinical problem when he made his report on thebiopsies so his comments were not biased by our views.I would emphasize that one does not necessarily have todemonstrate an abnormal appearance of the left vent-ricular cavity on angiography, although the appearanceof hypertrophied papillary muscles protruding into thecavity make the diagnosis much easier!

PROFESSOR J. GOODWIN: I never thought this patienthad HOCM because of the unimpressive angiogram andthis case clearly demonstrates that one cannot regardthe angiographic appearance as the final arbiter in thediagnosis. This patient really did have a restrictivepicture, hence the differential diagnosis from constrictivepericarditis. It is very unfortunate to miss constrictivepericarditis and I think that under these circumstancesthoracotomy has to be part ofthe investigative programme.DR OLSEN: I would like to emphasize that if one does

attempt a biopsy, it should be an open biopsy, it shouldbe clearly seen and it should be a reasonably largespecimen. A needle biopsy is completely useless from adiagnostic point of view.

PROFESSOR J. GOODWIN: We have experience of openbiopsy in four patients with congestive cardiomyopathyand the appearances were entirely non-specific. Theyalso did not indicate any specific causal aetiology.DR C. OAKLEY: It is important to understand that the

specific features of this disease are hypertrophy and lackof compliance of the myocardium. It is only when themyocardial hypertrophy is localized to a particular sitethat one gets obstruction and loud murmurs. Theobstructive element is only one aspect of the wholedisease problem. This patient did not really have thehaemodynamic features of constrictive pericarditis andif we had been a little more alert, we need not have donethe thoracotomy!

DR PETER TURNER (London): I would be interestedto know why this patient presented with gross tiicuspidregurgitation?DR C. OAKLEY: I don't know the answer! The right

ventricle could not be grossly dilated because the heartitself is not very large. The right ventricular cavitywill probably be small because she has a very largeinterventricular septum and an element of Bernheim'seffect comes into this. If in addition, because of theseptal hypertrophy the tricuspid ring and valve leafletsare displaced, opposition of the valves will not takeplace and we will have an incompetent valve witha small cavity, which will result in an extremely highfilling-pressure. I think this is probably what she had atthe time of presentation.DR FORSTER (Zurich): I don't think you have shown

that this patient did not have endocardial thickening, forthe symptoms would fit very well with the syndromewith eosinophilia demonstrated by my old teacher,Professor Loffler.DR C. OAKLEY: Certainly, mitral incompetence is not

uncommon in Loffler's cardiomyopathy, but this is theonly thing she had in common with Loffler's syndrome.There was no endomural thrombus, no emboli and noeosinophilia and the pathology was not that seen inLoffler's disease.DR OLSEN: In fact there was a little bit of endocardium

in this biopsy and it showed a little increase in endocardialthickening. Loffler found a considerable increase inendocardial thickening and a diffuse elastic pattern in theendocardial thickening which was not seen in this patient.DR WALLACE BRIGDEN: Was there any fibrosis in the

specimen?DR OLSEN: Yes, there was some fine fibrosis around

each individual myocardial fibre and some replacementfibrosis in the middle, but not a great deal.DR WALLACE BRIGDEN: I asked this question because

we have seen patients with a constrictive syndrome cometo necropsy with endocardial fibrosis of no more than1 mm at the thickest site. We have recently seen threepatients who had mitochondrial antibodies with minimalhepatic fibrosis, probably an early stage of biliarycirrhosis. In one patient, there was a thin lattice fibrosisin the heart and that patient had a raised venous pressure,some hepatomegaly but no ascites.DR C. OAKLEY: We have also seen two patients with

biliary cirrhosis who have had cardiac involvement andtricuspid incompetence; one had paroxysmal tachy-cardia and one had a pericardial effusion. We have notseen localized endocardial thickening produce compliancefailure of this sort on its own.DR WALLACE BRIGDEN: Do you think that the 'x'

descent in the venous pulse and the 'y' descent and therelationship between them are meaningful in this difficultdifferential diagnosis of pericardial constriction and myo-cardial disease? Did this patient have a steep or a shallow'x' descent?DR C. OAKLEY: I think the 'x' descent relative to the

'y' depends on factors other than the presence of tri-cuspid incompetence; it depends largely on the P-Rinterval as well, so we have not paid much attention to it.

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QUESTION: Have any hearts from people suffering fromthe Hamman-Rich syndrome come to necropsy and, ifso, is there any interstitial fibrosis in the heart?DR OLSEN: We have seen two or three such cases but

there was no increase in fibrosis in the hearts of thesepatients.DR A. POMERANCE: I have only seen two hearts in this

condition and they have been completely normal.

AddendumSome months later she came in as an emergency

with intestinal obstruction. Most of the smallintestine was gangrenous due to volvulus around anadhesion. She died after massive intestinal resection.

Necropsy: the left ventricular endocardium wasfound to be grossly thickened. The thickeninginvolved the inflow tract and apex but spared theoutflow tract which was separated by a fibrousendocardial ridge. Involvement of the chordae andpapillary muscles of the posterior mitral cuspexplained the mitral regurgitation. The heart thusshowed all the typical features of endomyocardialfibrosis but as she was an Irishwoman who hadnever lived outside Europe the appellation 'Loffler's'endomyocardial disease was given.

This case illustrates the ultimate importance of theangiographic appearance in diagnosis as well as theimportance of recognizing any features which do notfit with a favoured diagnosis. In HOCM a thirdheart sound is uncommon when compliance failureis the problem and the echocardiogram in thispatient showed a rapid diastolic closure slope whichwas also at variance with the physiological distur-bance of HOCM. Despite the rarity of the patient'sheart disease it should have been possible to arriveat the answer and it is of interest to note again thatLoffler's disease is not invariably associated witheosinophilia, embolism and endocardial thrombusformation.

Clinical association of skeletal muscular dystrophywith cardiomyopathy (Presented by Dr D. J. Coltart)

It is well recognized by physicians, and particularlyby neurologists, that patients with skeletal musculardystrophies often terminally exhibit cardiac de-compensation. It could be postulated that thissequence of events might be due to a generalizedmuscular dystrophy with early and serious mani-festations in the skeletal muscles and latterlyaffecting the heart. The reverse could therefore bepostulated for the cardiomyopathies with thegeneralized muscular dystrophic process havingearly and serious manifestations on the heart.The neuro-muscular diseases, Friedreich's ataxia,

progressive muscular dystrophy and myotoniaatrophica can all present with secondary cardiomy-opathies. 55% (thirty-three cases) of Friedreich's

ataxia exhibited some cardiac abnormality (Boyer,Chisholm& McKusick, 1962). Pathologically thiswasdemonstrated as either cardiac hypertrophy with fattyand eosinophilic degeneration or diffuse myocardialfibrosis with eccentric hypertrophy of both ventricles(Manning, 1950). During life, paroxysmal atrialarrhythmias are fairly common in these patients andthe electrocardiogram showed an abnormality in90% of patients being either left ventricular hyper-trophy, right ventricular hypertrophy or 2 :1 AVblock (Thor6n, 1964). The combination of motorinco-ordination simulating Sydenham's chorea and ofcardiac murmurs and electrocardiographic changesmay lead to an erroneous diagnosis of rheumaticfever with carditis. Progressive muscular dystrophieshave been reported to have an incidence of cardiacinvolvement ranging from 50 to 86% (Berenbaum &Horowitz, 1956) and this is demonstrated patho-logically with either myocardial fibrosis, fattyvacuolations with hypertrophy or atrophy (Storstein& Austarheim, 1955). The Duchenne type ofdystrophy very commonly has electrocardiographicabnormalities with tachycardia, right bundle branchblock and tall R waves in the right precordial leads(Gilroy et al., 1963). Q waves and non-specificrepolarization changes are observed. Sudden deathis also quitecommon (Berenbaum& Horowitz, 1956).The Erb type of limb-girdle-dystrophy frequentlyhas right ventricular conduction disturbances(Welsh, Lynn & Haase, 1963) and also terminallyprogresses to congestive heart failure. In patients withfacio-scapulo-humeral type of muscular dystrophy,electrocardiographic changes are infrequent (Perloff,1961) but there has been one case report of atrialstandstill (Bloomfield & Sinclair-Smith, 1965). Inmyotonia atrophica cardiac pathological findings aresparse and non-specific. Electrocardiographicchanges were reported in 62% of these cases withintraventricular conduction defect, prolonged PRinterval, left axis deviation and left bundle branchblock.

Case 7The first case illustrating the relationship of

muscular dystrophy with cardiomyopathy was a29-year-old female doctor. Two years ago her friendsfirst noticed some abnormality in her gait. Shepresented for medical attention 15 months ago withdifficulty in climbing stairs and on standing fromthe sitting position. She was found to have weaknessof the pelvic girdles and quadriceps and diminishedjerks in the leg. The neurologist who saw her atthat time diagnosed a limb-girdle-type musculardystrophy. Eleven months ago she noticed aninappropriate dyspnoea for the first time afterclimbing one flight of stairs. On examination at thattime there was a raised jugular venous pressure,

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728 Clinical demonstrations

some cardiomegaly and a gallop rhythm. The liverwas enlarged and therewassome sacral oedema. ChestX-ray demonstrated cardiomegaly and the investi-gations at that time showed a 15 / neutrophileosinophilia with an iron deficient blood picture.The serum creatinine phosphokinase and aldolasewere normal but an electromyogram indicated aprimary muscular dystrophy. A skeletal musclebiopsy confirmed the dystrophic process withatrophy, swelling and hyaline sarcoplasm in themyofibrils but no inflammatory cells. The patientwas treated with digoxin, diuretics and steroids withgood symptomatic improvement. Eight months agothe serum creatinine phosphokinase was found to be151 mVm/ml (normal upper limit is 50mim/ml). Five

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FIG. 1. Case 7. Muscle biopsy. Left quadriceps. Trichromestain. Histological stain shows widespead atrophy andhypertrophy of the muscle fibres with central nuclei andnuclear clumping. Some of the atrophic fibres are under-going degenerative changes. There is a marked increase inconnective and adipose tissue between the fibres. Noinflammatory changes are seen.

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FIG. 2. Case 7. Muscle biopsy. Left quadriceps. Histo-chemical stain shows that both Type 1 (light) and Type 2(dark) fibres are affected but no specific enzyme changeswere found.

months ago she had an attack of pulmonary oedemawith no ischaemic symptoms. The patient wasreferred to Professor Goodwin at the HammersmithHospital and on examination her facies suggestedsteroid administration, she was in sinus rhythm withcardiomegaly and on auscultation had third andfourth heart sounds with a mid-systolic murmur.The lung fields were clear and there was no peripheraloedema. On neurological examination she hadweakness of the glutei muscles, thigh adductors andquadriceps. The power was normal in the distalmuscle groups. She had slight weakness of bothdeltoids and triceps, normal power in the forearmsand hands. She had no weakness of any othermuscles, no fasciculation or muscle tenderness. Shehad sluggish arm reflexes, the knee jerks were absent,the ankle jerks present and plantar response wasflexor. There was no sensory defect. The investigationsshowed that she was still iron-deficient and the 15%eosinophilia persisted. The thyroid status wasnormal. The creatinine phosphokinase was raised to323 mtm/ml. The electrocardiogram showed sinusrhythm and left atrial hypertrophy and Q waves overthe left praecordium. Chest X-ray demonstratedcardiomegaly with clear lung fields. The shoulderX-ray and pelvic X-ray were normal. At cardiaccatheterization the left ventricular end-diastolicpressure was raised at 24 mmHg with a low cardiacindex. The left ventricular cine-angiogram showed apoorly contracting large left ventricle and normalcoronary angiograms, confirming the diagnosis ofcongestive cardiomyopathy. The electromyogramagain gave a dystrophic record. Sections from themuscle biopsy are shown in Figs. 1 and 2. Noobvious cause has been found to explain the eosino-philia which is now decreasing.Case 8A 36-year-old Italian restaurant-owner presented

with a short history of 6 months' exercise dyspnoeaand pulmonary oedema. He had weakness of hisleft arm and shoulder. His family history revealedsudden cardiac deaths in his mother and twobrothers unsupported by any post-mortem evidence.On examination he was mildly obese, had clinical

left ventricular hypertrophy with a third heartsound and minimal weakness of abduction of theleft arm and the left hip. Investigations showed araised serum creatine phosphokinase, 75 m,m/ml;electrocardiogram showed atrial fibrillation withleft anterior hemiblock pattern, left ventricularhypertrophy and repolarization changes. Chest X-rayshowed cardiac enlargement of left ventricularprominence and dilated upper lung vessels. Theleft ventricular cine-angiogram demonstrated alarge ventricular chamber with poor contractility, nothickness of the walls, no dyskinesia or aneursym

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Clinical demonstrations 729

and trivial mitral incompetence with an end-diastolicpressure of 18 mmHg. Coronary angiography wasnormal. Electromyography showed a diffuse patchymyopathy with brief duration polyphasic actionpotentials.

Case 9A 37-year-old male presented 1 year ago with an

ischaemic episode and paroxysmal supraventriculartachycardia. It was noticed that he had a wobblinggait with weak and wasted sternomastoids, spinati,biceps and triceps but normal distal muscles. Thecreatinine phosphokinase was grossly elevated at323 mVm/ml and his electromyograph showed highvoltage, short duration action potentials diagnosticof a primary myopathic process. He was referred toDr Oakley for cardiac evaluation. Thejugular venouspressure was markedly elevated with palpable leftventricular hypertrophy and a systolic murmur.Electrocardiogram was non-specific and chest X-rayshowed cardiac enlargement with early pulmonaryoedema. Whilst on the waiting list to be brought into be investigated the patient suddenly died at home.

AcknowledgmentsI am grateful to Dr John Durston of St Mary's

Hospital and the National Hospital, Queen Square,for his neurological advice and for the electromyogramsand muscle biopsies.

DiscussionDR COLTART: Meerschwam & Hootsmans (1971) in

Amsterdam were stimulated to look at the electromyo-graphs (EMG) of people with well-proven hypertrophicobstructive cardiomyopathy by the presence of provedcases of progressive muscular dystrophy among therelatives of two of their patients. In forty patients withwell-proven HOCM they havefound anabnormalEMG intwenty-six of these patients, sixteen had polyphasicaction potentials and the others had short mean motorunit action potentials. These abnormalities were positivelycorrelated with increase in age. None of these patientshad symptomatic weakness. Of thirty-one patients, fivehad raised CPK and of twenty-four patients studied, sixhad raised aldolase. These results suggest that in anappreciable number of patients presenting the clinicalpicture of HOCM, a generalized myopathy with earlyand serious cardiac manifestation should be consideredas a possible aetiological factor.DR M.J. DAVIES (London): We have examined muscle

histology at necropsy in a large series of subjects withcongestive cardiomyopathy, diagnosed in life as beingprimary and with no known skeletal muscle abnormality.In ten out of ninety cases there was definite histologicalevidence of a skeletal myopathy.DR COLTART: Have you examined a control group

with an equal degree of cardiac failure but not due tocardiomyopathy?

DR DAVIES: Yes, we routinely examine muscle fromcor pulmonale cases and in these we do not find similarchanges.

PROFESSOR J. GOODWIN: Perhaps one ought toemphasize that Meerschwam's work concerns hyper-trophic cardiomyopathy and not congestive cardiomyo-pathy and thus his findings do not relate to the materialDr Davies is describing.

Myocardial disease and acromegaly (Presented byProfessor John Goodwin)Case 10.The patient was a 51-year-old woman who com-

plained of dyspnoea on effort for 7 years. Onexamination she had acromegalic facies, considerablecardiac enlargement (of the left ventricle) and aregular pulse at 110/min. Jugular venous pressure8 cm above the sternal angle and third and fourthheart sounds; blood pressure 120/90 mmHg. Theelectrocardiogram showed grade 3 left ventricularhypertrophy and left anterior hemiblock.

Radiography of the pituitary fossa showed anexpanded sella turcica (Fig. 1) and biopsy revealedan eosinophil adenoma.

Cardiac catheterization revealed grossly im-paired cardiac function; left ventricular pressure137-174

mmHg; increased left atrial pressure6-33(mean) 38 mmHg; right atrial pressure (mean)8 mmHg ('v' wave 23,) cardiac index 2-71/min/m2.Left ventricular angiography showed mitral regurgi-tation, a large ventricular cavity and poor contrac-tion. Selective coronary arteriography was normal.The patient was treated for cardiac failure in theusual way, and an yttrium implant was placed in thepituitary fossa by Professor Russell Fraser.

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730 Clinical demonstrations

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O ."?.Ell b cC:FIG. 2. Frontal radiographs of the chest (6 ft). (a) November 1968. Nine months before pituitary implant, showing grosscardiomegaly, but no definite pulmonary congestion. (b) August 1969. Shortly before implant, showing increased left atrialpressure, some interstitial pulmonary oedema, and marked increase in the size of the pulmonary arteries. (c) October 1969.After implant, showing slight increase in heart size, but some reduction in interstitial oedema.

Most patients with acromegaly have large heavyhearts, which can generally be ascribed to persistenthypertension or coronary artery disease. But in ourexperience there are patients in whom cardiomegalyand heart failure occurred before hypertension, andwho died of heart disease despite treatment foracromegaly. Presumably therefore, excessive growthhormone may in some way cause irreversible cardiacdamage.DiscussionDR WALLACE BRIGDEN: YOU may be interested in a

minor historical comment. Professor Dorothy Russell ofthe London Hospital was interested in the cardiovascularmanifestations of the neuropathies and made a practiceof carefully examining the pituitary in every subject withcardiomegaly. I plotted out the heart weights of aconsecutive series of subjects with primary muscle diseaseand the two heaviest hearts, well over 1200 g, were bothacromegalic, one with hypertension and one withouthypertension.DR OLSEN: The increase in heart weight is not so much

due to myocardial fibre hypertrophy but to fibrous tissue.In fact, much of the myocardial tissue shows atrophy.DR A. POMERANCE: I have only seen one similar case,

with a heart weight about 800 g. Pathological changeswere minimal with a small increase in interstitial fibroustissue and rather large muscle fibres. My general impres-sion was that there was nothing particularly abnormalpresent!DR C. OAKLEY: Is Dr Olsen really suggesting that

these hearts have 700 g of fibrous tissue and 300 g ofmuscle?DR OLSEN: There is some hypertrophy away from the

fibrous area, but the bulk of the additional tissue isfibrous. Analysis of the constituents of these thickenedmyocardial fibres shows a large increase in collagencomponents.

PROFESSOR MICHAEL HUTT: Surely the weights of theselarge hearts in acromegalic subjects should be expressed

in relation to body weight? We think of idiopathiccardiomegaly as a heart which is abnormally heavy inrelationship to body weight. Most of the acromegalicsubjects are big heavy individuals and one wonderswhether a 1200g or 800 g heart is really that big inrelation to their size.DR B. MCKINNEY: I have recently looked at sections

of acromegalic heart and merely saw a slight increasein fibrous tissue, as described by Dr Pomerance. DoesDr Olsen know of any work measuring muscle fibre size?DR OLSEN: There are several ways in which this could

be done and which we have tried, both at light microscopyand electron microscopy level. It is painstaking and I donot know of any short way around it.

ReferencesBERENBAUM, A.A. & HOROWITZ, W. (1956) Heart involve-ment in progressive muscular dystrophy. American HeartJournal, 51, 622.

BLOOMFIELD, D.A. & SINCLAIR-SMITH, B.C. (1965) Persistentatrial standstill. American Journal of Medicine, 39, 335.

BOYER, S.H., CHISHOLM, A.W. & MCKUSICK, V.A. (1962)Cardiac aspects of Friedreich's ataxia. Circulation, 25, 493.

GILROY, J., CAHALAN, L.J., BERMAN, R. & NEWMAN, M.(1963) Cardiac and pulmonary complication in Duchenne'sprogressive muscular dystrophy. Circulation, 27, 484.

MANNING, G.W. (1950) Cardiac manifestations in Fried-reich's ataxia. American Heart Journal, 39, 799.

MEERSCHWAM, I.S. & HOOTSMANS, W.J.M. (1971) An electro-myographic study in hypertrophic obstructive cardio-myopathy. In: Hypertrophic Obstructive Cardiomyopathy.Ciba Foundation Symposium, J. & A. Churchill, London.

PERLOFF, J.K. (1961) Heart in progressive muscular dystrophyCirculation, 24, 1013.

STORSTEIN, O. & AUSTARHEIM, K. (1955) Progressive musculardystrophy of the heart. Acta medica scandinavica, 150, 431.

THOREN, C. (1964) Cardiomyopathy in Friedreich's ataxiawith studies of cardiovascular and respiratory function.Acta paediatrica, Suppl., 153, 1.

WELSH, A.D., LYNN, T.N. & HAASE, G.R. (1963) Cardiacfindings in 73 patients with muscular dystrophy. Archivesof Internal Medicine, 112, 199.

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BibliographyGACH, J.V., ANDRIANGE, M. & FRANCK, G. (1971) Hyper-

trophic obstructive cardiomyopathy and Friedreich'sataxia. American Journal of Cardiology, 27, 436.

LYNCH, P.G. (1971) Cardiac involvement in chronic poly-myosisis. British Heart Journal, 33, 416.

SOULIE, P. et al. (1966) Le coeur dans la maladie de Fried-reich; etude h6modynamique droite et gauche. Malattiecardiovasculari, 7, 369.

WAHI, P.L., BHARGAVA, K.C. & MOHINDRA, S. (1971) Cardio-respiratory changes in progressive muscular dystrophy.British Heart Journal, 33, 533, 1.

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