JACC Vol. 13, No. 6 1219 May 19X9:1219-39 ACC ANNIVERSARY SEMINAR Suzanne B. Knoebel, MD, FACC, G14est Editor The Challenge of Cardiomyopathy WALTER H. ABELMANN, MD, FACC, BEVERLY H. LORELL, MD, FACC Boston, Massachtrsrtts The combined clinical and pathophysiologic characteristics ease. Emphasis is placed on recent developments and and diagnostic features as well as current concepts of unresolved questions requiring application of newer tech- pathogenesis, therapy and prevention of the principal niques of molecular biology and genetics and adult myocyte forms of cardiomyopathy are reviewed. These include culturing. hypertrophic cardiomyopathy, dilated cardiomyopathy, re- (,I Am Co11Cardiol 1989;13:1219-39) strictive cardiomyopathy and specific cardiac muscle dis- “D’oti venons nous? Que sommes nous? Oti allons nous?” inent as causes of morbidity, disability and mortality. This Thus, Paul Gauguin entitled his monumental canvas of observation holds for a wide range of presentations and 1897, which addresses the human condition and life manifestations, such as decreased tolerance of activity, cycle. Since then, biomedical science has elucidated much congestive heart failure, arrhythmias, conduction distur- of this cycle and also has prolonged it for bances. chest pain and sudden death. :k: :..: .e; many individuals. If we look at the natural This article will not review present knowl- history of individual diseases, the same may . ...*..... edge and understanding of the cardiomyopathies be said for many diseases of heart muscle. in detail; many recent comprehensive reviews We know a great deal more about their origins are available (l-12). Rather, we shall emphasize and are able to recognize them earlier and recent contributions, try to present the high- more widely. Their life cycle has been extended. lights of our knowledge in perspective, ad- and we see the late stages with increasing fre- dress gaps of knowledge and understand- ANNIVERSARY quency. ing and raise questions to be addressed in the 1949-1989 Some afflictions of the heart have decreased future. in prevalence and importance. at least in the more developed countries, partly because of effective prevention or treat- ment, or both, and partly for reasons that are unclear. Historical Perspective Among these are syphilis, rheumatic fever, tuberculosis Disease of heart muscle. as distinct from valvular, coro- and malignant hypertension. On the other hand, diseases of nary, pericardial or congenital heart disease, was recognized heart muscle appear to be more prevalent either because as early as 1891by Krehl(13) in Germany, and reemphasized they have increased in incidence or because they are being in 1901 by Josserand and Gallavardin (14) in France and in recognized more frequently; they have become more prom- This article is port of u series of articles celebrating the 40th anniversury of the American College of Cardiology. From the Cardiovascular Division, Department of Medicine, Charles A. Dana Research Institute and the Harvard-Thorndike Laboratory of Beth The series crttempts to set the stage for the future by Israel Hospital. Beth Israel Hospital and the Harvard Medical School, describing current stute of the urt munagemcnt of selected Boston, Massachusetts. Dr. Lorell is supported by an Established Investiga- major curdiovascular problems and the basic knowledge torship of the American Heart Association, Dallas, Texas. Address for reorints: Walter H. Abelmann. MD, Cardiovascular Division. thut Mill provide directions for rrdvances in diagnosis and Beth Israel Hospital. 330 Brookline Avenue. Boston, Massachusetts 02215. therupy. cl989 by the American C‘ollcge of Cadiology l17~5-lO97!89/S3.50 1220 ABELMANN AND LORELL JACC Vol. 13, No. 6 CHALLENGE OF CARDIOMYOPATHY May 1989:1219-39 1933 by Christian (15) in the United States. However, it these disorders share common clinical, functional and patho- came into prominence and wide recognition only in the logic manifestations. Moreover, experimental models of second half of this century, thanks largely to the contribu- heart failure have shown a good deal of communality and tions by Mattingly (16), who reintroduced the term “primary overlap in the characteristics of individual forms of cardio- myocardial disease,” and Harvey et al. (17) in the United myopathy or specific heart muscle disease. Therefore, the States, and by Brigden (18), who introduced the term car- concept of cardiomyopathy as a pluricausal or multifactorial diomyopathy, and Goodwin and associates (19) in Great disease has gained increasing acceptance (2,5,23). The prin- Britain. Originally, the designation “primary” signified that cipal pathogenetic mechanisms under current consideration the disease predominantly affected the myocardium. Later, include genetic factors, metabolic disturbances, hormonal “primary” came to designate idiopathic afflictions of heart imbalances, toxins, calcium overload, altered vascular reac- muscle, as distinguished from diseases of other organ sys- tivity, hypoxia, free radicals, infection and immunelautoim- tems that affect the heart secondarily. mune processes. Classificationof cardiomyopathy. Initially, primary myo- cardial disease was considered a diagnosis of exclusion, that is, a diagnosis to be made after other etiologies had been Incidence and Prevalence of Cardiomyopathy ruled out. Gradually, it became recognized that there were In developed countries, the annual incidence of cardio- characteristic albeit nonspecific features that permitted rec- myopathy ranges from 0.7 to 7.5 cases per 100,000 popula- ognition of primary myocardial disease on its own merits. tion (24), and the prevalence in England has been reported as Furthermore, it became evident that there were different 8,317 cases per 100,000 population (25). At least 0.7% of groupings of structural and physiologic characteristics, lead- cardiac deaths in the United States have been attributed to ing to a functional classification first introduced by Goodwin cardiomyopathy (24); the male cardiomyopathy mortality is (19) and, in 1968, adopted by the World Health Organization twice that of female, and blacks have more than twice the (WHO) (20). This classification distinguished hypertrophic mortality rate of whites. It is generally believed that dilated cardiomyopathy with or without obstruction, initially known cardiomyopathy constitutes >90% of all cardiomyopathies in the United States as idiopathic hypertrophic subaortic encountered. stenosis (IHSS), from congestive cardiomyopathy and re- In less developed countries, especially in the tropics, strictive cardiomyopathy. In a later modification, the WHO cardiomyopathies are most prevalent and also constitute a (21) classification was altered in that “congestive cardiomy- greater if not dominant fraction of heart disease (24). This opathy” was relabeled “dilated cardiomyopathy”, and greater prevalence is largely in the form of dilated cardio- cases in which a specific etiology or associated systemic myopathy and to some extent of restrictive cardiomyopathy; disease could be identified were now assigned to a new it has been attributed variously to genetic factors, nutritional category of “specific heart muscle disease.” Furthermore, deficiency, infection including Chagas’ disease, physical two new categories, “obliterative cardiomyopathy” and stress, untreated hypertension, endomyocardial fibrosis and “indeterminate cardiomyopathy” were added. toxins such as ethanol (26). Heart muscle disease secondary to specific causes or disease entities (for example, thiamine deficiency, hemo- chromatosis, amyloidosis, muscular dystrophy) according to Hypertrophic Cardiomyopathy the WHO definition are no longer included among the Hypertrophic cardiomyopathy has held the fascination of cardiomyopathies. However, the similar clinical presenta- cardiologists despite its rarity because of its dramatic aber- tions and therapeutic problems have led to widespread rations of geometry and function and its importance as a continuation of the use of the term cardiomyopathy for such cause of disability and death in young, otherwise healthy cases, especially the frequently encountered entity of con- adults. Over the past 3 decades, our appreciation of the gestive heart failure secondary to chronic ischemic heart pleomorphic, geometric and hemodynamic manifestations of disease, generally referred to as “ischemic cardiomyopa- hypertrophic cardiomyopathy has greatly increased because thy.” The pragmatic advantage to the clinician of continuing of an enlarging body of natural history data and technologic to include congestive heart failure associated with specific advances in cardiac imaging. However, major gaps in knowl- heart muscle disease under the concept of dilated cardiomy- edge of the etiology and pathophysiology remain. This opathy has been previously discussed in detail (5). discussion will first present the historical perspective of the Pathogenetic mechanisms. The original concept that most initial disparate evolution and more recent convergence of idiopathic cardiomyopathies were attributable to a specific concepts regarding pathogenic mechanisms in hypertrophic cause, if one but searched long enough and awaited the cardiomyopathy. From this perspective, we will highlight results of further research, has had to be discarded. More major unanswered issues that require attention if further than 75 specific heart muscle diseases that may manifest as strides are to be made in the treatment of symptomatic dilated cardiomyopathy