heart which, in turn, are related to the progression of the disease.This is particularly critical for the correct identification of patients to be submitted to cardiac transplantation.The paper by Kell et al. shed some biological light on this important clinical problem; the presentation is very clear and unbiased, highlighting the limits and the potentialities of interleukin-6 in determining the risk stratification of patients with heart failure in NYHA class III.

Cardiomyopathies are myocardial disorders that are not secondary to coronary disease or hypertension or to congenital, valvular, or pericardial abnormalities.1 Classification is based on morphological and functional abnormalities, although overlap between groups is considerable. The four main types of cardiomyopathy are hypertrophic, dilated, restrictive, and arrhythmogenic right ventricular. Most heart muscle disorders affect mainly left ventricular structure and function, but the right ventricle is affected in arrhythmogenic right ventricular cardiomyopathy. I performed a literature search of all papers published in English in 1996 using Medline and the keywords cardiomyopathy and heart muscle disease. I searched the sections on cardiomyopathies and inflammatory disorders in volumes 10 and 11 (1995 and 1996) of Current Opinion in Cardiology and the supplement on the cardiomyopathies of the British Heart Journal (December 1994). Current Opinion in Cardiology lists the world literature annually and reviews subjects in which knowledge has advanced during the previous year. Earlier publications have been assimilated into current knowledge, and comprehensive coverage can be found in textbooks such as Diseases of the Heart .2 I selected papers on the basis of quality, relevance, and interest. The recent literature is extensive and has concentrated on understanding the molecular biology and pathogenesis of the disease rather than its drug treatment. Reliable data are scarce.3 Electrocardiographic and echocardiographic screening of defined populations showed that the prevalence of hypertrophic cardiomyopathy was between 1 in 500 and 1 in 5000 in the United States.4 Dilated cardiomyopathy accounts for between 1 in 50 and 1 in 25 cases of heart failure, most being secondary to coronary disease, hypertension, and valvular disease. #### Summary points A molecular pathogenesis for dilated and hypertrophic cardiomyopathy is beginning to be elucidated More than half of patients with hypertrophic cardiomyopathy and a quarter of patients with dilated cardiomyopathy have familial disease Known …

OBJECTIVE--To investigate the molecular genetic basis of the cause of disease in a family with hypertrophic cardiomyopathy. BACKGROUND--Mutation within the beta cardiac myosin heavy chain gene has been shown to be the pathogenetic mechanism underlying the disease in several families, though clear evidence of heterogeneity has been reported. PATIENTS--A family with a history of hypertrophic cardiomyopathy. RESULTS AND CONCLUSION--This paper reports a mutation at aminoacid position 908 within exon 23 of the beta cardiac myosin heavy chain gene, resulting in a conversion of a leucine to valine. This base substitution was identified in an individual with a confirmed family history but with equivocal symptoms of the disease. Inheritance of the mutation by his symptom free juvenile offspring demonstrates the application of the technique to presymptomatic diagnosis.

Between 50 and 70% of patients with heart failure die suddenly and unexpectedly before they have deteriorated to New York Heart Association class IV symptoms. It has long been known that ventricular ectopy predicts sudden cardiac death in coronary heart disease, and this has also been shown in dilated cardiomyopathy. It is less certain whether antiarrhythmic drugs reduce this risk and improve prognosis. Supraventricular arrhythmias frequently develop in heart failure of all causes. They nearly always cause symptoms, and the establishment of atrial fibrillation may mark a permanent deterioration. Except for sustained ventricular tachycardia, ventricular arrhythmias are often occult. Hypokalemia and digitalis toxicity may have been precipitated by diuretics or interaction with antiarrhythmic drugs. In coronary heart failure, arrhythmias may be related to scar tissue or ischemia, which may also be responsible in dilated cardiomyopathy. Use of inotropes and inodilators may precipitate arrhythmias, whereas drugs that conserve energy or potassium, such as beta blockers and angiotensin-converting enzyme inhibitors, may prevent them. Since suppression of ventricular arrhythmias has not been shown to prevent sudden death or prolong life in patients with heart failure, it may be that such arrhythmias do not directly presage ventricular fibrillation except in so far as they are markers of a poor prognosis with a risk of sudden death. If so, such arrhythmias are most likely to be suppressed by agents that result in improvement of left ventricular function and, through that, prolongation of life.

Failure of the right ventricle may be due to a congenital anomaly, intrinsic disease, pulmonary stenosis or pulmonary hypertension. Left ventricular failure may also lead to right ventricular failure if the heart fails totally or secondary to pulmonary hypertension, or if filling of the right ventricle is decreased due to left ventricular dilation or hypertrophy. Treatment of right ventricular failure has yielded disappointing results, except when caused by left ventricular failure that responds to therapy. Digitalis and diuretics may have more adverse than beneficial effects. In patients with both left and right ventricular failure, survival is usually less than 2 years.

The long term performance characteristics of the 2400 and 1260 series of Starr-Edwards aortic prostheses were investigated by a follow up study of clinical outcome of 327 patients discharged from hospital with isolated aortic valve replacement. Follow up lasted for up to 10 years and was based on 1616 patient-years. The 2400 series cloth covered tracked valve was implanted in 182 patients from 1974 to 1980 and the 1260 series bare strut silastic ball valve was inserted in 145 patients from 1979 to 1983. Total 10 year mortality and valve related morbidity were low and no cases of mechanical valve failure were recorded. There were no significant actuarial differences in mortality or valve related morbidity between the 2400 and 1260 valves. Starr-Edwards models 2400 and 1260 aortic valve prostheses showed excellent durability without any mechanical failures over a 10 year period. The long term outcome of isolated aortic valve replacement with these models is associated with a low frequency of valve related complications.

Patients with native valve endocarditis treated surgically between 1968 and 1978 (n =15) and all patients presenting with prosthetic valve endocarditis during this period (n=21) were followed up for at least four years.Five of the patients with native valve endocarditis required urgent early surgical intervention, of whom two died.The remaining 10 underwent valve replacement after a course of antibiotic treatment: all survived, though one required further valve replacement.The 21 patients with prosthetic valve endocarditis suffered 25 attacks.Nine were cured by medical treatment alone; two died before surgical intervention was possible; 11 required valve replacement, of whom three died; and two required valve replacement after a course of antibiotic treatment.The incidence of early prosthetic valve endocarditis- that occurring within two months of operation-was 0-67%, but that of late prosthetic valve endocarditis could not be determined.Medical treatment when started early should cure endocarditis in most patients, but vigilance should be maintained for the appearance of indications for surgery.When such indications exist surgery should not be delayed.

In order to examine the association between arrhythmia and subsequent prognosis, 72-hour ambulatory electrocardiographic monitoring was performed in 86 unselected patients with hypertrophic cardiomyopathy. During monitoring 23 patients experienced at least one episode of supraventricular tachycardia and 24 had ventricular tachycardia (of whom 10 had more than three episodes). The patients were then followed for a mean of 2.6 years (range one to four). Seven patients died suddenly. Of these, five had exhibited multiform and paired ventricular extrasystoles and ventricular tachycardia. These arrhythmias were significantly associated with sudden death whereas supraventricular arrhythmias were not. The patients who died suddenly were older and had experienced more symptoms than the survivors, and three had a family history of hypertrophic cardiomyopathy and sudden death. This experience provides the basis for the assessment of treatment in patients with hypertrophic cardiomyopathy and serious ventricular arrhythmia.