journal, the cardiomyopathies - heart · ' secondary' cardiomyopathies, thoughuseful,...

Editorial

British Heart Journal, I972, 34, 545-552.

The cardiomyopathies

J. F. Goodwin' and C. M. Oakley'

Despite world-wide endeavour during thepast decade the pathogenesis of the cardio-myopathies remains unknown. This majorissue has largely been obscured by over-concentration on classification while the pro-duction of enormous lists of those diseasesthat may affect heart muscle has often madeconfusion worse confounded.Our original definition, 'A subacute or

chronic disease of heart muscle of unknown,or obscure aetiology often with associatedpericardial and endocardial involvement butnot due to atherosclerosis', was too complex,while the later division into 'primary' and' secondary' cardiomyopathies, though useful,could not be used to cover all cases and causedsome confusion.

Therefore it is suggested that the wordcardiomyopathy' should be reserved forthose disorders previously described as 'pri-mary cardiomyopathy', and that the term'secondary cardiomyopathy' should be aban-doned, diseases in this group being classifiedaccording to the underlying disease, etc.(Goodwin, 197ia).The definition of cardiomyopathy becomes

much simpler: 'a disorder of heart muscle ofXinknown cause or association' (Oakley,I97ia). This definition emphasizes that incardiomyopathy the myocardial disorder isapparently a primary event. The practice ofusing the term 'ischaemic cardiomyopathy'to describe the myocardial disorder due toischaemic coronary artery disease cannot, inour view, be too greatly deplored.Our new classification based on functional

pathology is as follows:

Congestive: characterized by poor systolicfunction.

1 Address: Department of Medicine (Clinical Cardi-ology), Royal Postgraduate Medical School, Hammer-smith Hospital, London W.12.

Hypertrophic (with or without obstruction):characterized by impaired diastolic compli-ance.Obliterative: characterized by obliteration ofthe ventricular cavities.

The category of constrictive (obliterative)cardiomyopathy should now be abandoned asthis clinical group is virtually confined to thespecific heart muscle diseases, mainly primaryamyloid, and occasionally leukaemic infiltra-tion or polyarthritis nodosa (Goodwin, I964).

In temperate zones the obliterative type isso rare that in practice attention should befocused upon two main types: congestive andhypertrophic, for the vast majority of cardio-myopathies in Great Britain are of one orother of these types.

Thus, of 224 patients with cardiomyopathy,so defined, studied at the Royal PostgraduateMedical School from i960-i970, 102 werecongestive, I20 were hypertrophic, and only2 were obliterative (one endomyocardial fibro-sis and one Loffler's fibroblastic 'endocar-ditis' with eosinophilia).

Congestive cardiomyopathyCongestive cardiomyopathy is recognized bypoor systolic function ('pump failure'). Leftventricular ejectile force is diminished, bloodbeing incompletely ejected from the ventriclesso that the heart dilates. Since heart failurewith congestion is the end-result of any dis-order of the left ventricular muscle, it is par-ticularly important in this group to excludehypertensive and coronary artery disease aswell as all the known toxic and metaboliccauses of left ventricular failure and constric-tive pericarditis.The clinical picture is one of low output

congestive heart failure, with cardiomegalyand filling gallop rhythm. Haemodynamicand angiographic studies show increased

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546 Goodwin and Oakley

systolic and diastolic ventricular volumes andaugmented diastolic pressures. Naked eyenecropsy studies show a dilated flabby ven-tricular mass, with appreciable hypertrophy,much of which is hidden by the dilatation.The coronary arteries are strikingly normaland do not exhibit more than minimal degreesof occlusive atheroma (Gau et al., I970).Dilatation occurs as a result of severe ventricu-lar damage and it has been suggested that theusual process of compensatory hypertrophymay be diminished (Goodwin, 1970). Cer-tainly patients with greater than usual hyper-trophy tend to live longer than those withless hypertrophy (Kristinsson et al., I968;Oakley, I97Ib).

Pathogenesis In congestive cardiomyo-pathy, epidemiology and geographical path-ology, though important, have been unsuc-cessful in shedding any further light on theorigin of heart muscle disease. Field work, asexemplified by that of Miall and his colleagueshas directed attention to the frequency ofheart muscle disorder in Jamaica (Fodor et al.,I964), and there is every reason to believethat the incidence in Jamaica is not greatlyhigher than that in most other countries ofthe world. The incidence in 'developed'countries is probably not much less than inunderdeveloped countries, but recognition isclouded in sophisticated societies whereischaemic heart disease is common and likelyto be preferred as the diagnosis when heartdisease affects patients in the coronary agegroup.

It is now known that angina is experiencedby about I0 per cent of patients with con-gestive cardiomyopathy and that a so-called'infarct pattern' on the electrocardiogram isno guarantee of discrete infarction secondaryto ischaemia (Gau et al., I970). Though clini-cal assessment may weight the scales heavilytowards or away from a diagnosis of conges-tive cardiomyopathy or coronary artery dis-ease, the distinction may only be made withcertainty after selective coronary angiographyand left ventricular angiography have beencarried out.A relation between systemic hypertension

and congestive cardiomyopathy exists (Kris-tinsson, I969; Goodwin, I970), and it has tobe accepted that some hypertensive patientswith left ventricular failure differ only inbeing hypertensive from patients with conges-tive cardiomyopathy (Oakley, I97Ib). Thisremains true at both clinical and pathologicallevels of assessment, and epidemiological evi-dence shows that hypertension and congestive

cardiomyopathy are both common in the samepopulations (Fodor et al., I964). The con-tribution of hypertension to the aetiology ofcongestive cardiomyopathy has recently beenkeenly debated (Oakley, I97ia; Goodwin,I97ib).The role of previous virus infections

(Sainani, Krompotic, and Slodki, I968) hasbeen well substantiated in only a small pro-portion of patients with congestive cardio-myopathy. All the Coxsackie B viruses andalso Echo 9, Echo 6, Echo 30, and influenzaA2 viruses have been incriminated in the causeof acute myocarditis and, though Bengtsson(I968) and Somerville (I968) have shown thatsome patients progress to a chronic myocar-dial disorder, it seems unlikely that previousviral infections account for the developmentof chronic congestive cardiomyopathy in morethan a small proportion of patients. Certainlyno trace of previous infection, viral, bacterial,or protozoal has been found in the heartmuscle of our patients with congestive cardio-myopathy, either in biopsy specimens or afterdeath.The role of alcohol has been even more con-

troversial. Excessive alcohol intake has threepossible associations with myocardial dis-order: (I) cobalt poisoning in heavy beerdrinkers; (2) thiamine deficiency in alcoholicswith grossly inadequate diets; (3) cardiomyo-pathy attributable to the alcohol itself.The first two are accompaniments of alco-

holism. Cobalt poisoning can lead to heartfailure in the absence of alcohol, and proteinmalnutrition sensitizes the myocardium to theeffect of the cobalt. The cause and effectrelation of cobalt has now been amply proven.Cobalt was included in the secret formula ofbrewers in Quebec, in Belgium, and possiblyalso in other parts of the world as a stabilizerof the froth on beer. The uncovering of itsrole as the cause ofan epidemic ofheart failureamong beer drinkers is a fascinating story(Kesteloot et al., I968; Mercier and Patry,I967; Morin I967). It was only by the in-gestion of such huge quantities of beer thatvirtually no other source of calories was takenand protein intake was inadequate that thequantity of cobalt in the beer assumed impor-tance and brought about myocardial failure.

Beri-beri heart disease is virtually non-existent in Great Britain as it is difficult toavoid the ingestion of adequate thiamine evenon the meanest diet. Thiamine deficiency isusually associated with a high cardiac outputand eventual heart failure. Thus beri-beri isusually different from the low output heartfailure seen in the cobalt cases or in congestivecardiomyopathy, but can occasionally occur

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The cardiomyopathies 547

with a low cardiac output ('dry' or Shoshinberi-beri) (McIntyre and Stanley, I971).

It is still uncertain whether or not excessiveconsumption of ethyl alcohol itself leads tocongestive cardiomyopathy. The protagon-ists (Brigden and Robinson, I964; Burch andDePasquale, I968; Alexander, I966; Tobinet al., 1967; Seftel, 197I; Regan, I97I) note ahigh incidence of heavy drinking in patientswith congestive cardiomyopathy and assertthat some patients improve with abstinencebut that few can be so persuaded. A clearassociation of congestive heart failure withheavy alcoholic intake and its relief after stop-ping alcohol in the Bantu in South Africa hasbeen described by Seftel (I97I). Heavy de-position of neutral lipids throughout the myo-cardium and some electron microscopicalappearances have been alleged to be specific(Hibbs et al., I965; Alexander, I966, I967).

Others doubt the direct causal connexionbetween alcohol and heart muscle disease orbelieve that alcohol may be but one of manyconditioning factors which may lower theresistance of the myocardium to noxiousagents as yet unknown. Most adults in thiscountry take alcoholic drinks. We have foundno difference in the drinking habits of patientswith congestive cardiomyopathy comparedwith patients with other heart diseases. Ahistory of heavy alcoholic intake (at least 4pints of beer or 375 ml of spirits daily forseveral years) was found in only i6 of 74patients studied by Kristinsson (I969). Wehave not seen haemodynamic improvementafter undoubted withdrawal of alcohol overa period of months. The consensus nowamong pathologists is that there are no differ-ences in the light microscopical, ultrastruc-tural, or histochemical appearances betweencardiomyopathies of assumed alcoholic causa-tion and those whose origin is unknown.An acute depressant effect of alcohol on

left ventricular dynamics has been shown(Riff, Jain, and Doyle, I969), but this ofcourse provides no evidence that alcohol canalso cause permanent and irreversible heartfailure. Burch stated recently (I97I) that ratswho ingested ethyl alcohol equivalent to 'aquarter of their weight for a quarter of theirlives' failed to develop any cardiomyopathy.The mechanism by which alcohol has been

thought to bring about myocardial damage isquite unknown, but it has been suggestedthat acid aldehyde, the principal first meta-bolite of alcohol, stimulates the release of nor-adrenaline from nerve endings in the myo-cardium and thus leads eventually to deple-tion ofmyocardial noradrenaline stores (Jamesand Bear, I967). This argument is hard to sus-

tain when it is known that drugs which depletecatecholamines such as reserpine and guane-thidine do not bring about heart failure in theotherwise healthy heart, but excessive cate-cholamine action can damage the heart (VanVliet, Burchell, and Titus, I966).The non-selective deterrent effect of alco-

hol on enzyme induction in the liver may bemirrored in similar actions within the myo-cardium but the controversy over the role ofalcohol in the genesis of cirrhosis is almost asunsettled as the arguments over its role in thegenesis of cardiomyopathy.The occurrence of heart failure and evi-

dence of congestive cardiomyopathy duringthe later stages of pregnancy or in the puer-perium has given rise to the term 'peripartumcardiomyopathy'. Common features aremultiparity and malnutrition and a tendencyfor recurrence in subsequent pregnancies(Walsh et al., I965; Demakis and Rahim-toola, I97I). This condition occurs rarely inmore privileged communities and we haveseen only 7 patients in a series of 74 patientsanalysed by Kristinsson (I969).Postpartum or peripartum cardiomyopathy

may represent a multifactorial illness inwhich pregnancy is only one factor. In a re-cent patient the heart failure was associatedwith fulminating toxaemia of pregnancy, andParry (I971, personal communication) hassuggested an association in patients in North-ern Nigeria.

It seems likely that the pathogenesis ofcongestive cardiomyopathy is also multifac-torial and that the diagnosis denotes not adisease but an end-result of which there maybe many causes. The rarity in our experienceof any genetic influence is striking and pointsto an acquired infective or toxic cause.Emanuel, Withers, and O'Brien (I97I) in acollaborative study between the Institute ofCardiology, the Middlesex Hospital, and theRoyal Postgraduate Medical School noted asmall number of familial cases of apparentcongestive cardiomyopathy, which might beexplained by an inherited immunological de-fect which rendered the heart vulnerable tothe development of an acquired cardiomyo-pathy of the congestive type.

Treatment There have been no new ad-vances in the treatment of congestive cardio-myopathy. The mainstays are still bed rest,digitalis, and diuretics. Burch has advocatedprolonged bed rest for up to a year (Burch,Walsh, and Black, 1963). At present there isno haemodynamic evidence of permanent im-provement in myocardial performance aftersuch long periods of rest, but it is certainly

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possible that in at least some patients the re-duction of left ventricular work may give timefor the myocardium to compensate by gainingadequate hypertrophy of its wall. Steroids donot influence the course of the disease. Theeffects of inotropic agents such as glucagonare being studied by our group.

Pericardectomy has been tried but therationale is uncertain; an increase in heart sizeafter pericardial release is unlikely to bebeneficial in these already overstretched heartsfor the Frank-Starling mechanism may notapply at these high volumes. Nevertheless, ithas been postulated that the heart may becomerestricted against a tight pericardium, or thatassociated pericardial effusion may cause somedegree of tamponade.

In our experience of four patients who weretreated by partial pericardial release, haemo-dynamic improvement as judged by subse-quent cardiac catheterization occurred inonly one, though three improved clinicallyafter the operation.

Recently Lewis, Barnard, and Brink (I9971)described dramatic effects after completepericardectomy in four patients. Their resultssuggested a more favourable myocardial fibrelength-tension relation with increased com-pliance but without enhanced contractility.If the problems of cardiac transplantation aresolved before satisfactory medical treatmentis available then transplantation should seri-ously be considered for these patients.

Hypertrophic cardiomyopathyHypertrophic (obstructive) cardiomyopathyused to be recognized only when left ventricu-lar hypertrophy and muscular outflow tractobstruction coexisted. Indeed, this deter-mined the early names for the disorder; ob-structive cardiomyopathy (Goodwin et al,I960) and subsequently hypertrophic ob-structive cardiomyopathy (Cohen et al., I964)in Great Britain, idiopathic hypertrophic sub-aortic stenosis (Braunwald et al, I960) andmuscular subaortic stenosis (Wigle, Heim-becker, and Gunton, I962) in North America.It is now known that obstruction to left ven-tricular ejection is not an invariable featureof the disorder, nor present throughout thelifetime of individual patients. The myocar-dial hypertrophy which characterizes the dis-order cannot be attributed to an increase inwork load but appears to be a primary featureof the abnormal myocardial cell. Functionally,nypertrophic cardiomyopathy is character-ized by a diastolic failure of the left ventricledue to a loss of its normal distensibility. Thiscan be contrasted with the systolic 'pump

failure' of congestive cardiomyopathy inwhich hypertrophy is secondary and compen-sates for cavity dilatation. In hypertrophiccardiomyopathy the cavity of the left ventricleis of normal size in diastole, but in systole itoften appears to be reduced in size (Grant etal., I968) and of abnormal shape due to en-croachment on the lumen of a hypertrophiedseptum and papillary muscles.

Left ventricular outflow tract obstructiontends to be a feature of those patients in whomleft ventricular hypertrophy is most asym-metrical, with major involvement of the sep-tum and relatively less hypertrophy of thefree wall. Obstruction may be absent inpatients who have massive thickening of thefree wall and in these patients the disorderappears to be more widespread, more severe,and the prognosis correspondingly worse.The height of the left ventricular end-diastolicpressure marks the severity and extent ofmyocardial involvement. The end-diastolicpressure is intensely labile, varying greatlywith small changes in end-diastolic volumeand rising steeply with sympathetic stimula-tion during exercise or emotion (Webb-Pep-loe et al., I971).The left ventricle fills slowly, as shown by

Stewart, Mason, and Braunwald (I968), as aresult of the ventricular hypertrophy whichproduces a rigid noncompliant chamber. Re-striction of diastolic filling time due to tachy-cardia aggravates the fault, with a resultingdramatic increase in leftventricularend-diasto-lic pressure and left atrial pressure which leadto dyspnoea, and in some cases to pulmonaryoedema. Syncope may also be due to this cause(Goodwin, I970; Webb-Peploe et al., I97I).

Mitral regurgitation is usually associatedwith outflow tract obstruction and may alsobe variable because both are attributable toanterior dislocation of the anterior mitral cuspwhich moves into the cavity and towards theseptum during systole (Pridie and Turnbull,I968), thereby both blocking the outflow tractand rendering the mitral valve regurgitant.This abnormal movement does not occur inthe patients without outflow tract obstruction(Shah, Gramiak, and Kramer, I969; Pridieand Oakley, I970).We believe that the raised left ventricular

end-diastolic pressure not only reflects theseverity of the disease but is the main deter-minant of symptoms and prognosis (Swan etal., I97I). Reduction of left ventricular inflowrestriction and increase in the rate of filling ofthe left ventricle has since been realized to bethe major aim of treatment rather than solelyrelief of outflow tract obstruction (Oakley,I97Ic).

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qatural history Progression of the dis-)rder may be associated with spontaneous loss)f outflow tract obstruction. This is attribut-Lble to impairment of systolic contractile'unction with an increase in systolic volume.Since there appears to be no increase in end-liastolic volume, even a small fall in ejection'raction considerably affects the stroke volumemd results in a profound reduction in cardiac?erformance.Recent studies on the natural history of

hypertrophic cardiomyopathy have revealed3pontaneous loss of outflow tract obstructionin 8 of 42 patients who have been followed foraver 5 years. The systolic murmur became-less or disappeared in all, and this course wasassociated with an increase in dyspnoea and inheart size. Atrial fibrillation occurred in I5patients and was accompanied by an increasein central venous pressure and by deteriora-tion in symptoms. Systemic embolism oc-curred in 9 of these patients and heart failurein I2 patients, including the 3 who had pul-monary oedema. Five patients died in con-gestive heart failure. Analysis of symptomaticprogress in 85 of our patients and of factors4associated with sudden death suggested thatpatients who had a short history of symptomswhich were progressive and who had a highleft ventricular end-diastolic pressure have apoorer prognosis than those with a long stablemildly symptomatic course and little increasein pressure at rest. Outflow tract obstructionappeared to have no relation to the occurrence,of sudden death (Swan et al., 197I). Childrenwithout outflow tract obstruction but with ahigh left ventricular end-diastolic pressureappear to do especially poorly.

Treatment Left ventricular outflow tractobstruction, being the first functional abnor-mality to be recognized, was also the first to'be attacked. Surgical incision or excision ofthe hypertrophied septum is usually success-"ful in its aim of eradicating the outflow tractgradient (Bentall et al., I965; Morrow et al.,I968). Symptoms are often improved, butobjective evidence for improvement other thanreduction in the outflow tract obstruction isstill lacking, though Morrow et al. reported areduction in mitral regurgitation and in rest-.ing left ventricular end-diastolic pressure,suggesting an improvement in myocardialfimction. The significance of disappearance ofoutflow tract gradients after operation isdifficult to assess in view of the spontaneousloss of outflow tract obstruction during thenatural course of the disorder that has been.shown to be associated with a distinctdeterioration. No postoperative studies have

yet been carried out which show any improve-ment in cardiac output on exercise or an in-crease in stroke volume for the same or a lowerend-diastolic pressure as compared with thepreoperative state. Improvement in late prog-nosis and in long-term survival have also notyet been shown to result from operation. Sofar in I7 of a series of 25 patients who havebeen operated upon at the Royal PostgraduateMedical School between I958 and I970, therehave been 4 late deaths, i from acute leftventricular failure, i from infective endocar-ditis, and 2 sudden deaths. Three patientshave developed atrial fibrillation and 2 havehad systemic emboli. All these patientsshowed a persistently high left ventricularend-diastolic pressure.

Early interest in beta adrenergic blockingdrugs derived from suggestions of left ven-tricular hyperkinesis, and of excess endogen-ous catecholamine activity which have notbeen confirmed (van Noorden, Olsen, andPearse, I97i). The jerky arterial pulse wasoriginally thought to be due to excessivelyrapid ejection due to enhanced catecholamineaction, but in fact the pulse is abrupt and illsustained primarily because of a systolic dipwhich coincides with the onset of outflowtract obstruction and the cessation of rapidejection. The pulses are normal in hypertro-phic cardiomyopathy when obstruction is mildor absent. The total systolic function of the leftventricle is relatively well maintained through-out the course of the disease in most cases.Nevertheless, there does appear to be an ab-normal response to sympathetic stimulationin hypertrophic cardiomyopathy. Isoprenalinecauses a rise in left ventricular end-diastolicpressure which is an almost specific featureof this disorder and which contrasts with thefall or lack of change which is seen both in thenormal left ventricle and in other forms of leftventricular disease and which contrasts alsowith the fall in end-diastolic pressure whichoccurs in hypertrophic cardiomyopathy whenthe rate is increased by pacing (Webb-Peploeet al., I97I). It is for these reasons that drugswhich block the cardiac actions of adrenalinemay be particularly helpful in the treatmentof this disorder.Angina is usually improved by beta adrener-

gic blocking agents in hypertrophic cardio-myopathy as in ischaemic heart disease bylimitation of exercise-induced tachycardia andreduction of its oxygen consumption. Exercisein untreated cardiomyopathy is frequentlyassociated with an excessive tachycardia butfall in stroke volume (Edwards et al., I970).The beta adrenergic blocking drugs bringabout an increase in stroke volume but with

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the fall in rate this is insufficient to improvethe poor circulatory response to exercise.The left ventricular end-diastolic pressure

in hypertrophic cardiomyopathy is as labileas the outflow tract obstruction and it is thesharp rise in end-diastolic pressure on exer-cise, together with reduction in left ventricu-lar filling time, which are responsible fordyspnoea. Webb-Peploe et al. (197I) showedthat practolol reduced end-diastolic pressureon exercise, even when given in a dose whichdid not slow the heart. It seems that eventhough the bradycardiac action of these drugshas value, the left ventricular end-diastolicpressure lowering effect must be attributed tosome other action.The paradoxical effects of isoprenaline and

practolol on end-diastolic pressure have beenattributed to their effects on left ventriculardistensibility (Webb-Peploe et al.), but otherpossibilities should be considered. Eitherlengthening of the PR interval or left atrialfailure could explain the fall in post a waveleft ventricular end-diastolic pressure inducedby beta receptor blockade, but in hypertrophiccardiomyopathy there is an abnormally steeprise in LV diastolic pressure at low volumesduring early filling. It is lowering of this pres-sure, in addition to reduction in post a wavepressure, which supports the suggestion thatfilling of the left ventricle is facilitated by betaadrenergic blockade.As a result of these haemodynamic studies

and of the preliminary results of a double-blind trial (Hubner et al., 1972) we recom-mend that beta adrenergic blocking drugsshould be prescribed for all patients withhypertrophic cardiomyopathy as soon as thediagnosis has been proved and regardless ofthe presence and extent of incapacity, or ofoutflow tract obstruction. Indeed, since pa-tients without outflow tract obstruction mayhave a severe form of the disorder and a sig-nificant chance of sudden death, they arelikely to benefit most from therapy. Syncopeand sudden death are thought to follow anepisode of tachycardia which has broughtabout even greater curtailment of left ven-tricular filling, a more profound fall in strokeoutput and blood pressure, and a more criticaldecrease in coronary blood flow. Beta adrener-gic blocking agents should help to preventthese fatal complications of hypertrophiccardiomyopathy.The dose should be high; our experience

has been that patients tolerate this group ofdrugs well and that children particularlyshould be prescribed a higher dose than wouldbe calculated on a weight basis. We suggest upto 320mg daily ofpropranolol or 8oo mg daily

of practolol in adults. We have not used ox-prenolol or alprenolol but there seems to beno reason why these drugs should not beequally effective.Although the onset of atrial fibrillation

usually marks the onset of serious deteriora-tion, some patients become stable again andlive for many more years. Deterioration afterthe development of atrial fibrillation is likelyfor several reasons. Since its onset is relatedto the height of the left atrial pressure thepatients who develop atrial fibrillation usuallyhave the most advanced left ventricular com-pliance failure and the lowest stroke volumes.Atrial fibrillation is likely to be associatedwith a further fall in stroke output due to lossof the enhanced atrial contribution to ven-tricular filling. Irregular diastolic intervalsfurther limit left atrial emptying and the leftatrial pressure may rise further. Finally,systemic embolism is a high risk (Swan et al.,I971).

Anticoagulants should therefore be startedurgently and continued for an indefiniteperiod in patients who develop atrial fibrilla-tion, and also in those patients who give ahistory suggestive ofparoxysmal atrial fibrilla-tion.

Beta adrenergic blocking drugs are notcontraindicated at the onset of heart failure,and digoxin is not contraindicated in atrialfibrillation since at this stage outflow tractobstruction is usually absent. Digoxin ofcourse may increase the outflow tract gradientin classical hypertrophic cardiomyopathy insinus rhythm (Braunwald, Brockenbrough,and Frye, I962). Control of ventricular ratein atrial fibrillation can be attempted withbeta adrenergic blocking drugs alone butdigitalis is valuable in addition. Digoxin to-gether with a beta adrenergic blocking agentcan sometimes produce a dramatic fall in ven-tricular rate, The maintenance dose ofdigoxin for the control of atrial fibrillationneed not usually exceed 025 mg daily anddigitalis should be given cautiously and underobservation.

Infective endocarditis can complicate thedisorder (Frank and Braunwald, I968) and themain problem in our experience has been de-lay in diagnosis because of lack of awarenessof this complication (Vecht and Oakley, I968).

Pregnancy is surprisingly well tolerated(Turner, Oakley, and Dixon, 1968). Eighteenof our patients with cardiomyopathy havebeen supervised during 22 pregnancies afterthe diagnosis of their cardiac disorder. All thepregnancies were successful and all the pa-tients are still living. Propranolol was giventhroughout pregnancy to 20 patients and

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practolol to the other 2. No undue slowing ofthe foetal heart rate was noted at any stageand no adverse effect on uterine contraction(was noted, nor was there any excessive post-partum haemorrhage. Caesarian section wasreserved for obstetric indications but thesecond stage was expedited when necessary.It is our practice to continue propranololduring labour, giving it intramuscularly ifnecessary, and an intravenous infusion is setup at the onset in case drugs need to be givenquickly or blood has to be replaced, for thesepatients withstand haemorrhage poorly. Anti-biotic cover is given and lactation is not sup-pressed because the concentration of pro-pranolol in the milk is too low to be importantto the infant.

a Eugenic considerations obviously apply,but only a few of our patients have elected toadopt children on this account. There is asyet no evidence that the so-called sporadiccases will not equally transmit the disorder totheir children, thus showing up a previouslyhidden genetic fault. We have not advisedagainst pregnancy except where there is astrong family history but perhaps this policyshould now be revised.

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Analysis of Ioo cases with special reference tochronic alcoholism. American Journal of Medicine,41, 213.

Alexander, C. S. (I967). Electron microscopic obser-vations in alcoholic heart disease. British Heartjournal, 29, 200.

Bengtsson, E. (I968). Myocarditis and cardiomyo-pathy. Cardiologia, 52, 97.

Bentall, H. H., Cleland, W. P., Oakley, C. M., Shah,P. M., Steiner, R. E., and Goodwin, J. F. (I965).Surgical treatment and post-operative haemo-dynamic studies in hypertrophic obstructive cardio-myopathy. British Heart Journal, 27, 585.

Braunwald, E., Brockenbrough, E. C., and Frye, R. L.(I962). Studies on digitalis. V. Comparison of theeffects of Ouabain on left ventricular dynamics invalvular aortic stenosis and hypertrophic subaorticstenosis. Circulation, 26, i66.

Braunwald, E., Morrow, A. G., Cornell, W. P.,Aygen, M. M., and Hilbish, T. F. (I960). Idio-pathic hypertrophic subaortic stenosis. AmericanJ7ournal of Medicine, 29, 924.

Brigden, W. W., and Robinson, J. F. (I964). Alcoholicheart disease. British Medical Journal, 2, I283.

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Burch, G. E., Walsh, J. J., and Black, W. C. (I963).Value of prolonged bed rest in management ofcardiomegaly. J7ournal of the American MedicalAssociation, I83, 8i.

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Edwards, R. H. T., Kristinsson, A., Warrell, D. A.,and Goodwin, J. F. (I970). Effects of propranololon response to exercise in hypertrophic obstructivecardiomyopathy. British Heart journal, 32, 2I9.

Emanuel, R., Withers, R., and O'Brien, K. (I97I).Dominant and recessive modes of inheritance inidiopathic cardiomyopathy. Lancet, 2, I065.

Fodor, J., Miall, W. E., Standard, K. L., Fejfar, Z.,and Stuart, K. L. (I964). Myocardial disease in arural population in Jamaica. Bulletin of the WorldHealth Organization, 31, 32I.

Frank, S., and Braunwald, E. (I968). Idiopathic hyper-trophic subaortic stenosis. A clinical analysis of I26patients with emphasis on the natural history.Circulation, 37, 759.

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Hubner, P., Lane, G., Ziady, G., Oakley, C. M., andGoodwin, J. F. (I972). Double blind trial of pro-pranolol and practolol in hypertrophic obstructivecardiomyopathy. To be published.

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Kesteloot, H., Roelandt, J., Willems, J., Claes, J. H.,and Joossens, J. V. (I968). An enquiry into the roleof cobalt in the heart disease of chronic beerdrinkers. Circulation, 37, 854.

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Lewis, C. M., Barnard, P. M., and Brink, A. J. (I97I).The haemodynamic basis for penicarditis on pallia-tive treatment of idiopathic endomyocardiopathy.In Proceedings of International Symposium onCardiomyopathies and Cardiac Metabolism, Bellville,South Africa, October 1971. To be published.

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McIntyre, N., and Stanley, N. N. (I97I). Cardiac beri-beri: two modes of presentation. British MedicalJ7ournal, 3, 567.

Mercier, G., and Patry, G. (I967). Quebec beer-drinkers' cardiomyopathy. Clinical signs and symp-toms. Canadian Medical Association journal, 97,884.

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Morrow, A. G., Fogarty, T. J., Hannah, H., III, andBraunwald, E. (I968). Operative treatment in idio-pathic hypertrophic subaortic stenosis: techniques,and the results of preoperative and postoperativeclinical and haemodynamic assessments. Circula-tion, 37, 589.

Oakley, C. M. (I97ia). The cardiomyopathies. AtInternational Society of Cardiology Symposium,held at the Royal Postgraduate Medical School,London, October Z97I. To be published.

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Pridie, R. B., and Oakley, C. M. (I970). Mechanismof mitral regurgitation in hypertrophic obstructivecardiomyopathy. British Heart Journal, 32, 203.

Pridie, R. B., and Turnbull, T. A. (i968). The aeti-ology of mitral valve dysfunction as revealed byultrasonics. In Proceedings of the Vth EuropeanCongress of Cardiology, Athens, September I968,pp. 263-272.

Regan, T. J. (197i). Ethyl alcohol and the heart.Circulation, 44, 957.

Riff, D. P., Jain, A. C., and Doyle, J. T. (I969). Acutehaemodynamic effects of ethanol on normal humanvolunteers. American Heart journal, 78, 592.

Sainani, G. S., Krompotic, E., and Slodki, S. J. (I968).Adult heart disease due to the Coxsackie virus Binfection. Medicine, 47, I33.

Seftel, H. C. (I97i). Treatment of cardiomyopathy inJohannesburg. In Proceedings of InternationalSymposium on Cardiomyopathies, Bellville, SouthAfrica, September I97I. To be published.

Shah, P. M., Gramiak, R., and Kramer, D. H. (I969).Ultrasound localization of left ventricular outflowobstruction in hypertrophic obstructive cardio-myopathy. Circulation, 40, 3.

Somerville, W. (I968). Myocarditis and myocardio-pathy. In Proceedings of the Vth European Congressof Cardiology, Athens, September 1968.

Stewart, S., Mason, D. T., and Braunwald, E. (I968).Impaired rate of left ventricular filling in idio-pathic hypertrophic subaortic stenosis and valvularaortic stenosis. Circulation, 37, 8.

Swan, D. A., Bell, B., Oakley, C. M., and Goodwin,J. F. (197I). Analysis of the symptomatic courseand prognosis and treatment of hypertrophic ob-structive cardiomyopathy. British Heart Journal,33, 671.

Tobin, J. R., Driscoll, J. F., Lim, M. T., Sutton, G. C.,Szanto, P. B., and Gunnar, R. M. (I967). Primarymyocardial disease and alcoholism. The clinicalmanifestations and course of the disease in aselected population of patients observed for 3 ormore years. Circulation, 35, 754.

Turner, G. M., Oakley, C. M., and Dixon, H. G.(I968). Management of pregnancy complicated byhypertrophic obstructive cardiomyopathy. BritishMedical Journal, 4, 28I.

Van Noorden, S., Olsen, E. G. J., and Pearse, A. G. E.(197I). Hypertrophic obstructive cardiomyopathy;a histological, histochemical, and ultrastructuralstudy of biopsy material. Cardiovascular Research,5, ii8.

Van Vliet, P. D., Burchell, H. B., and Titus, J. L.(I966). Focal myocarditis associated with pheo-chromocytoma. New England Journal of Medicine,274, I102.

Vecht, R. J., and Oakley, C. M. (I968). Infective endo-carditis in three patients with hypertrophic obstruc-tive cardiomyopathy. British Medical Journal, 2,455.

Walsh, J. J., Burch, G. E., Black, W. C., Ferrans,V. J., and Hibbs, R. G. (I965). Idiopathic myo-cardiopathy of the puerperium (postpartal heartdisease). Circulation, 32, I9.

Webb-Peploe, M. M., Croxson, R. S., Oakley, C. M.,and Goodwin, J. F. (I971). Cardio-selective beta-adrenergic blockade in hypertrophic obstructivecardiomyopathy. Postgraduate Medical Journal,47, Suppl., January, 93.

Wigle, E. D., Heimbecker, R. O., and Gunton, R. W.(I962). Idiopathic ventricular hypertrophy causingmuscular subaortic stenosis. Circulation, 26, 325.

Requests for reprints to Professor J. F. Goodwin,Department of Medicine (Clinical Cardiology),Royal Postgraduate Medical School, Hammer-smith Hospital, London W. I2.

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journal, the cardiomyopathies - heart · ' secondary' cardiomyopathies, thoughuseful,...

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