Approaches to prevention and early detection of cardiomyopathies: Memorandum from a WHO Meeting*

Me7orada are state-. Les Mc ru m ments concerning the exposent les conclu- Mci,, u~~rwni conclusions or recom- sions et recomman- mendations of certain dations de certaines WHO scientific meet- reunions scientifiquesMeIVIDmn nFrlwloranau s ings; they are signed MdelOMS; its sontby the participants in signcs par les partici- the meeting. pants i ces reunions. Bulletin of the World Health Organization, 64 (3): 36S-374 (1986) 0 World Health Organization 1986 Approaches to prevention and early detection of cardiomyopathies: Memorandum from a WHO Meeting* A meeting on cardiomyopathies was held in Geneva on 25-27 March 1985 to review the state of understanding concerning these diseases and to update the information and recommendations contained in the published report of the WHO Expert Committee on Cardiomyopathies which had met in 1983. Particular emphasis was given to discussing new scientific knowledge, priorities for etiological research, proposals for cooperation between research centres in developed and developing countries, early detection of cardiomyopathies, and possible population studies related to the disease. REVIEW OF NEW SCIENTIFIC KNOWLEDGE The conclusions and recommendations contained in the report of the WHO Expert Committee on Cardiomyopathies (1) remain valid. The sections below bring up to date the information contained in that report. Frequency of cardiomyopathy The increased frequency of diagnosis of dilated cardiomyopathy (CMP) is largely attributable to increased clinical recognition of the condition. This is partly due to wider dissemination of knowledge about CMP and partly to the increased sensitivity and availability of invasive and non-invasive diagnostic methods, particularly echocardiography. Hyper- trophic CMP is being diagnosed with increasing frequency in elderly individuals (2), but at the same time the frequency of at least one form of specific 0 This Memorandum is based on the report of a WHO Consultation (unpublished document WHO/CVD/85.6) (1), which was held in Geneva on 25-27 March 1985. A list of the participants is given on page 371. Requests for reprints should be addressed to Cardiovascular Diseases Unit, World Health Organization, 1211 Geneva 27, Switzerland. A French translation will appear in a later issue of the Bulletin. heart muscle disease, Keshan disease in China, has decreased (3). Pathogenesis of cardiomyopathy Dilated cardiomyopathy. Increasingly, past viral infections are being recognized as causal factors in a significant proportion of patients with dilated CMP (4, 5). A number of studies have reported that acute experimental viral myocarditis can lead to chronic CMP as a complication (6, 7), and that this com- plication can be prevented in mice infected with encephalomyocarditis virus by induction of either active or passive immunity (8). This experimentally induced disease can be significantly modified or even prevented by early treatment with antiviral agents such as ribavirin (9) or interferon (10). On the other hand, the important role played by the immune and autoimmune processes in experimentally induced subacute and chronic myocardial diseases following viral infection has been fully established by a wide array of laboratory studies, as well as by a number of investigations in man (11). The recognition that dilated CMP is a pluricausal or multifactorial disease is gaining increasing accep- tance (12). Based upon studies of cardiomyopathy in 4674 -365- MEMORANDUM Syrian hamsters, it has recently been proposed that alterations in the micro-vasculature, and specifically vascular spasm, are potential pathogenetic factors (13). Lesions of the autonomic nervous system may have pathogenetic significance in cases of dilated CMP (14), and reduced numbers of subepicardial ganglion cells have been reported (14) as well as alter- ations in catecholamine activity (15). It is clear that ventricular arrhythmias play a significant role in the natural history of dilated CMP, especially in the high incidence of sudden death (16). Alteration of dia- stolic function has become recognized as an important factor in dilated as well as in restrictive and hypertrophic CMP (17). Hypertrophic cardiomyopathy. Genetic factors appear to operate in the majority of cases of hyper- trophic CMP. Ventricular arrhythmias, especially ventricular tachycardia, carry a poor prognosis and are associated with sudden death (18, 19). Endomyocardial fibrosis. The specific role of de- granulated eosinophils in the pathogenesis of endo- myocardial fibrosis -irrespective of an etiological association with eosinophilia - has been firmly established; however, the pathogenetic mechanism(s) remain to be elucidated. Chagas' disease. Considerable progress has recently been made in our understanding of Chagas' disease and an in-depth update of such progress would be timely. It is recommended that this be done under the aegis of the Pan American Health Organization. Severe alterations of the autonomic nervous system involving the heart and other organs have been observed in experimentally induced and natural cases of Trypanosoma cruzi infection; however, the mechanism of the neuronal destruction in this disease is not known. Direct neuronal parasitism does not explain extension of the neuronal lesion. It has been suggested that in the acute stage the rupture of a nest of tissue parasites releases antigen that can become associated with the surface membrane of surrounding uninfected cells. These parasite-modified host cells could be damaged by elements of the anti-T.cruzi immune response, thus releasing auto-antigens that induce immunological responses and determine the autoimmune reactions against neurons. In this respect, a number of aspects related to the host- parasite relationship in animal models have recently been described (20). Diagnosis of cardiomyopathy With the rapidly increasing use of endomyocardial biopsy in the evaluation and study of patients with CMP, it has become recognized that inflammatory lesions occur in 3-25Oo of such patients (21, 46). To ensure uniform criteria for the histopathological diagnosis of myocarditis, especially with regard to the study of therapeutic interventions, a group of cardiac pathologists met in 1984 and proposed strict guide- lines (22, 47). Positive diagnosis of active myocarditis requires the presence of a myocardial infiltrate associated with damage to adjoining myocytes, which is not typical of ischaemia. A subsequent biopsy is compatible with ongoing myocarditis, should the lesions be as or more extensive than in the previous biopsy; less extensive lesions support a diagnosis of resolving or healing myocarditis, while disappearance of inflammation, with or without fibrosis, indicates resolved or healed myocarditis. Biopsies have also been found valuable in diagnosing specific diseases of the heart muscle such as haemochromatosis, amyloid disease, sarcoidosis, Fabry's disease, and other myo- cardial diseases, as well as in the detection of trans- plant rejection and of early anthracycline toxicity (23). Gallium scans of the heart have also been valuable adjuncts to the clinical diagnosis of myo- cardial inflammation in some instances. (24). Regional myocardial dysfunction is now well recognized as not infrequent in cases of acute myocarditis as well as in dilated CMP (12, 25). Echocardiography, especially in the two-dimensional mode, is superior to roentgenography in detecting early dilatation of cardiac chambers; and it can also be used to differentiate regional from global dys- functions and quantitate the latter, as well as to detect pericardial effusion and intracardiac thrombi. Radio- ventriculography (gated nuclear scan) permits analysis of biventricular function in resting and exercising patients. Prolonged ambulatory monitoring facilitates detection of significant cardiac arrhythmias and, occasionally, conduction disturbances in many patients with CMP who are not aware that they have the condition and whose diagnostic electrocardio- gram does not reveal these episodic manifestations. Acute pericarditis with characteristic electrocardio- graphic abnormalities is frequently associated with some degree of myocarditis (26) and the extent and significance of this involvement may be determined using the non-invasive techniques mentioned above. Treatment of cardiomyopathies Dilated cardiomyopathy. The newer vasodilator drugs, e.g., captopril, afford symptomatic relief and haemodynamic improvement in cases of congestive heart failure (27), and regression of myocardial cellular hypertrophy has also been reported (28). There is, however, no evidence that the prognosis is influenced. Newer, non-glycoside inotropic agents, 366 PREVENTION AND EARLY DETECTION OF CARDIOMYOPATHIES such as milrinone (29), which are still under investigation, have, in addition, strong vasodilator properties. They also have striking clinical and haemodynamic benefits, but do not affect the prognosis favourably. The use of beta-adrenergic blocking agents in the treatment of dilated CMP remains controversial. Most observations have been made in uncontrolled studies, and the few controlled trials have been small and give conflicting results (30, 31). Cardiac transplantation remains an appropriate therapy for individuals in the late stages of dilated CMP that resist conventional medical approaches. The results are as good or better than those resulting from replacement of hearts affected by ischaemic heart disease (32). Hypertrophic cardiomyopathy. Although treat- ment with beta-adrenergic blocking agents or calcium antagonists may afford symptomatic relief, use of these drugs does not result in regression of cardiac hypertrophy or change its long-term prognosis. Amiodarone, which is moderately effective against ventricular arrhythmias, but is also toxic, may improve the short-term prognosis (33). Endomyocardialfibrosis. There have been no new developments in the therapy of endomyocardial fibrosis. PRIORITIES FOR ETIOLOGICAL RESEARCH Dilated cardiomyopathy It is hoped that the increased understanding of pathogenesis and improved treatment ofCMP facili- tated by endomyocardial biopsies will be enhanced by the use of other techniques, such as characterization of the types of inflammatory cells using monoclonal antibodies, additional immunopathologic studies, histochemical studies, and the analysis of myocardial receptors. Studies should be made of experimental models of viral myocarditis and CMP as well as of other forms of chronic CMP. In addition to such in vivo studies, investigations using preparations of isolated perfused hearts, papillary muscles, and cultured cardiac myocytes should be considered. The effects of alcohol intake and of dietary deficiencies, e.g., of vitamin B1 (thiamine), upon such preparations also require further study. Genetic aspects of dilated CMP should be explored in man and animals using current methods of molecular biology. Investigations already carried out on the genetic aspects of hypertrophic CMP should be extended to dilated CMP. Further work is needed to identify the viruses and strains of viruses responsible for human myocarditis and to analyse differences between the myocardial effects of different cardiotropic viruses. Modern methods in virological research, such as enzyme- linked immunosorbent assay (ELISA) (34), should be used. As mentioned previously, increasing evidence supports the infectious-immune theory of patho- genesis of dilated CMP, and active myocarditis has been demonstrated increasingly frequently by endo- myocardial biopsy of patients with dilated CMP of recent onset. This has led to fairly extensive trials of immunosuppressive regimens of the type that have been successful in suppressing or preventing rejection of cardiac transplants, usually a combination of aza- thioprine and prednisone. Many patients thus treated have improved clinically or recovered (21); however, none of these studies was conducted under controlled conditions, and the results are also compatible with the natural history of viral myocarditis. An inter- national, multicentre, controlled study of immuno- suppressive therapy of biopsy-proven myocarditis following the viraemic phase is in the final planning stages (35). Patients will be randomly assigned to one of three regimens: azathioprine and prednisone; ciclosporin A and low-dose prednisone; or conven- tional therapy (control). High priority will be given to similar controlled trials of immunosuppressive therapy of patients with biopsy-proven myocarditis; however, in view of the known toxic effects of some of these unproven therapies, their further uncon- trolled use is not recommended. General acceptance of standards of preparation and interpretation of endomyocardial biopsies, like that proposed by the International Panel of Pathologists of 1983 (47), is recommended to facilitate these trials. If the value of viral vaccines (8) and antiviral agents (9, 10) is borne out in further studies involving experimental models, the way would be open to conduct preventive intervention trials in humans to avert cases of acute outbreaks of cardiotropic viral infections. Hypertrophic cardiomyopathy Further investigations should be carried out to settle whether human leukocyte antigen is associated with hypertrophic CMP. The hypothesis should be tested that hypertrophic CMP is caused by depletion of cyclic AMP or an altered density of receptors as a consequence of increased levels of norepinephrine (36). For this purpose, quantitative studies of myo- cardial alpha- and beta-adrenergic receptors should be carried out. The role played by catecholamines in this form of CMP should be explored by studying the uptake of radiolabelled catecholamines using positron emission tomography. 367 MEMORANDUM Endomyocardial fibrosis The association between endomyocardial fibrosis and altered eosinophils has been established for temperate zones, but not yet uniformly for the tropics. The mechanisms of degranulation of eosino- phils remain to be established, and the reasons for their different geographical distributions and seasonal variations should be explored. Further studies of the potential diagnostic value of mono- clonal antibodies in this respect should be pursued. Specific heart muscle diseases Chagas' disease. Studies using monoclonal anti- bodies and investigations of serology and cell- mediated immunity have indicated antigenic cross- reactions between host and parasite (37). In this respect, the feature of the parasite that initiates the autoimmune response should be identified, using the techniques of immunochemistry and molecular biology. Peripartum heart disease. The role of viral infections (myocarditis) in this syndrome merits further study, and more work on the development of vaccines should be carried out. Keshan disease. An animal model of this disease in swine has been developed in China (3). The model reproduces the cardiac, hepatic, and skeletal-muscle necrosis characteristic of the disease, which can be prevented by administration of selenium (3). The mechanism whereby selenium deficiency produces these lesions should be studied, as well as the role played by selenium in the metabolism and function of the normal heart. The potential importance of selenium deficiency in dilated CMP in various geo- graphical areas should be explored. Other treatable deficiency diseases. The occurrence of cardiac beriberi as a consequence of thiamine deficiency, which may be an added pathogenetic factor in CMP, should be considered wherever high prevalence of heart failure is noted. Patients on restricted diets, those taking large doses of diuretics (38), or those having an increased demand for thi- amine, e.g., in pregnancy, growth, hyperthyroidism, are at risk. Carnitine deficiency should be considered in cases of familial CMP (39) where levels of this amino acid in plasma and tissue are low. Endomyocardial biopsy usually reveals fibroelastosis, and the condition is treatable using L-carnitine administered orally. Proposals for close cooperation between centres in developed and developing countries Existing multicentre studies of dilated CMP and of endomyocardial disease, established under the auspices of the Scientific Council on Cardiomyo- pathies of the International Society and Federation of Cardiology (ISFC), could serve as models for additional collaborative studies between centres in developed and developing countries. While individual initiative and motivation are important, institutional agreement and commitment are required to ensure the success of such projects over a period of time. If such collaborative research is to result in optimal progress towards better understanding of the causes and pathogenesis of CMP, and in improved therapy as well as prevention of the disease, efforts must be multidisciplinary, involving cellular, subcellular, and molecular biology, immunology, virology, toxi- cology, biochemistry, pharmacology, and epi- demiology, in addition to medicine and paediatrics. Researchers working at the forefronts of these disci- plines must be recruited to contribute to these efforts. Workshops may be effective in this respect, and it is recommended that close cooperation between WHO and the ISFC be continued. EARLY DETECTION OF PATIENTS WITH CARDIOMYOPATHIES The detection ofCMP in its earliest, asymptomatic or latent stages is important for studies of the natural history of the different forms of the disease, as well as to facilitate its secondary prevention and, when available and appropriate, early therapy. Dilated cardiomyopathy For research purposes and early detection, a limited number of individuals may be screened using the methods given below. From a clinical point of view, attention must be directed toward those individuals most likely to develop CMP, and subjects may be selected on the basis of a high-risk profile for dilated CMP: this includes acute viral illness, exposure to alcohol, and a positive family history of CMP. Early signs of CMP include cardiovascular manifestations such as cardiomegaly, arrhythmias (40), electrocardiographic abnormalities, unex- plained cardiomegaly on routine roentgenography, or unexplained arterial embolism. Chest pain is also not an uncommon presentation of dilated CMP (41), and exertional dyspnoea may be the earliest symptom. Initial screening should include a full cardio- vascular history, involving exercise tolerance and a thorough cardiovascular examination, as well as searches for abnormal ventricular impulses, S3 and S4 gallops, and increased venous pressure. Screening 368 PREVENTION AND EARLY DETECTION OF CARDIOMYOPATHIES should include an electrocardiogram. If abnormali- ties are found, these may be followed up and clarified diagnostically be means of echocardiography, ambu- latory monitoring of the electrocardiogram, nuclear imaging or exercise stress tests, cardiac catheter- ization, angiography, and endomyocardial biopsy, depending on clinical indications. If the clinical picture suggests active myocarditis, or if the CMP is of recent onset, endomyocardial biopsy may be necessary to confirm this diagnosis. Hypertrophic cardiomyopathy Whereas a normal electrocardiogram may be recorded even for relatively advanced dilated cardio- myopathy, abnormal electrocardiograms are usual in the early stages of hypertrophic cardiomyopathy, and this observation is therefore important in its early detection. However, there are many other reasons for an abnormal electrocardiogram, and echocardi- ography remains the single most important diag- nostic test for hypertrophic cardiomyopathy. An increased ratio of the thickness of the septum to the thickness of the left ventricular free wall is the cardinal sign of the disease; however, cardiac hyper- trophy may be concentric in as many as 50%o of cases (42). Relatives of patients with hypertrophic CMP constitute the population at greatest risk of develop- ing this form of the disease. Endomyocardialfibrosis The early clinical manifestations of endomyo- cardial fibrosis are not well known, although studies are in progress. Echocardiographic abnormalities tend to appear late in the course of the disease. In tropical countries, children below 10 years of age living with families of low socioeconomic status and with a high prevalence of malnutrition are pre- dominantly affected. The presence of degranulated eosinophils in significant numbers in the peripheral blood (> 15% of the total eosinophil count) is strongly indicative of the disease; however, in the later stages of endomyocardial fibrosis degranulated eosinophils may not be detectable in peripheral blood. In developed countries, endomyocardial biopsies have detected degranulated eosinophils even in the absence of eosinophilia. Indeed, in these countries, it has been established that the earliest stage of endomyocardial fibrosis is myocarditis, with the presence of degranulated eosinophils in the infiltrate. The potential value of gallium scans in the early diagnosis of this disease therefore merits exploration. Special training in the recognition of degranulated eosinophils is required, and a simple illustrated manual would be useful for this purpose. Chagas' disease In 90% of cases of Chagas' disease the initial acute parasitic myocarditis would have occurred during the first decade of life (37). At this time, most affected individuals live in the rural areas where access to medical services is limited, e.g., in some South American countries, so that an early diagnosis cannot be made. However, for those who live in urban or suburban slum areas, early diagnosis is feasible and may lead to use of chemotherapy and a subsequent reduction of parasitaemia. Furthermore, as exercise has been shown to be deleterious in experimentally induced murine trypanosomiasis (43), control of physical activity may be beneficial for human sufferers. After a latent period characterized by the absence of symptoms and clinical signs, Chagas' disease becomes manifest, usually between the second and fourth decades of life (42). The challenge lies in identifying afflicted individuals during the latent period of the disease, when the heart size and electrocardiogram tend to be normal; however, there is little motivation to take up this challenge at present, in the absence of any effective therapy. During the manifest clinical phase of Chagas' disease, the approach to diagnosis may be similar to that used in the early detection of dilated CMP (see above), although this has contributed little if anything to the better management of the disease. Keshan disease Although the acute form of Keshan disease has become rare, it is occasionally encountered in children or in pregnant women. Manifestations of the disease include acute left ventricular failure and cardiogenic shock (3). In as much as the lesions tend to be subendocardial, endomyocardial biopsy may be useful and merits exploration. Special considerations concerning non-invasive methods in the early diagnosis ofcardiomyopathies Whereas all non-invasive cardiac diagnostic methods potentially have a role in the study and diagnosis of CMP, echocardiography (both M-mode and two-dimensional) can be singled out for its broad applicability to all forms of the disease. Although mobile instruments of relatively light weight for echocardiography are widely available, they are not suitable for heavy-duty field use or in the tropics. It is therefore recommended that instruments, which are easy to maintain and which have an independent power source, be developed for this purpose. Simpli- fication of operational procedures to facilitate train- ing of appropriate staff would also be desirable. 369 370 MEMORANDUM Development of simplified systems for ambulatory monitoring of electrocardiograms and processing of magnetic tapes would be beneficial, although tapes could be sent to central locations for processing. Al- though longer periods have been suggested, the valid- ity of monitoring patients with CMP for periods shorter than 24 hours should be examined. If this were acceptable, the method would find wider application. A "points" system for diagnosing cardiomyopathies The WHO Expert Committee on Cardio- myopathies (1) proposed that a "points" system based on clinical features might be helpful in the early diagnosis and identification of cases. In order to explore this possibility, it is proposed that the cardiac profile of different types of CMP be correlated with the definitive diagnosis, as established in referral centres. Annex 1 shows a tabulation that should serve as a basis for developing such a "points" system. FEASIBILITY OF POPULATION STUDIES ON CARDIOMYOPATHIES The design of and methods used in population surveys should be adapted to the particular population and questions addressed, and should include surveys of well defined total populations, randomized and stratified samples, as well as surveys of well defined subsets of populations. Two examples of such surveys were discussed at the meeting. A sample of randomly selected individuals from a homogeneous population is to be surveyed electrocardiographically. In this sample, 1500 ab- normal electrocardiograms are predicted. Each patient with an abnormal electrocardiogram would then be evaluated in depth, starting with echo- cardiography and other non-invasive and invasive studies, if indicated. Where appropriate, ischaemic heart disease is ruled out using an exercise stress test and coronary angiograms. A subset of patients with high-grade ventricular ectopy might then be identified and could be used for a controlled study of the potential effect of amiodarone upon course and survival (44). The second example discussed was a study proposed for an area where endomyocardial fibrosis is endemic, and the disease becomes manifest in patients in their mid-teens. A prospective study is proposed of 100 subjects of age 14-15 years with circulating degranulated eosinophils identified during a survey of a much larger population using both electrocardiography and echocardiography. Such a survey is expected to yield new information on the frequency and natural history of endomyocardial fibrosis. Attention is drawn to a population study that has just been completed in England of patients with overt dilated cardiomyopathy (45). Other possible population studies The potential, wide geographical and regional variability in the absolute and relative frequency of different types ofCMP was recognized. This calls for select worldwide studies, preferably of geographically defined, stable populations with access to specialized centres. Standardized protocols, previously devel- oped by WHO for studies of hypertension, rheumatic heart disease, and ischaemic heart disease, should be consulted for guidance. Two protocols, designed by the ISFC for registering dilated CMP and endomyo- cardial fibrosis, have also been used and reference copies are available.a Populations at high risk, once identified, might become priority candidates for such studies. National mortality and hospital discharge statistics might be helpful in the selection of popu- lations at high risk. Repetitions of such surveys at intervals would yield valuable information on the natural history of CMP. CONCLUSIONS AND RECOMMENDATIONS 1. Scientific knowledge on CMP was reviewed and the information contained in the published report of the WHO Expert Committee on Cardiomyopathies (1) has been updated. The general conclusions in that report remain valid. 2. The infectious-immune theory of the etiology of dilated CMP has been further strengthened by new evidence. Increased application of modern viral diagnostic methods is recommended. In addition, the important role of endomyocardial biopsy in further clinical and investigative approaches was stressed, as well as the need for acceptance of standards for histopathological interpretation. The value of endo- myocardial biopsy might be enhanced by further extension of immunological and histochemical studies. Controlled studies of immunosuppressive therapy of active myocarditis are also urgently needed as are similar studies of beta-adrenergic blocking agents in the therapy of dilated CMP. The effects of alcohol upon the myocardium in the con- text of dilated CMP must always be taken into account. Finally, the genetic aspects of dilated CMP merit further study. 3. For hypertrophic CMP, attention was drawn to the probable role of catecholamines in the disease, the need to quantify catecholamine receptors in normal a Requests should be addressed to Dr D. Amorim, Chairman, Council on Cardiomyopathies, Rua Barao de Lucena 115, Ap. 605, CEP 2260, Botafogo, Rio de Janeiro, R.J., Brazil. PREVENTION AND EARLY DETECTION OF CARDIOMYOPATHIES 371 and abnormal hearts, and the potential value of positron emission tomography. In future, the molecular aspects of the genetic transmission of hypertrophic CMP should be studied. 4. The detailed mechanism of degranulation of eosinophils should be explored and such studies have already been initiated in southern India. Further- more, the geographical distribution and seasonal variation of degranulation of eosinophils merit study. 5. For Chagas' disease, further studies are indicated of the mechanism of initiation of the auto- immune response. 6. The probable significant role of myocarditis in peripartum CMP requires further study. 7. The role played by selenium in cardiac metabolism and function should receive greater attention, together with investigation of the patho- genesis of Keshan disease. 8. Etiological research as well as studies of the natural history and therapy of CMP would greatly benefit from close cooperation between research centres in developed and developing countries. Participation by researchers working at the vanguard of their respective fields should be encouraged. 9. The importance of early detection of CMP was emphasized with respect to the need for better information about its frequency and natural history as well as the possible application of secondary pre- vention. Of the many diagnostic methods available, the value of echocardiography, ambulatory electro- cardiographic monitoring, and endomyocardial biopsy was highlighted. The usefulness of gallium scans and of nuclear magnetic resonance studies needs to the clarified by further study. 10. Epidemiological studies of CMP in well- defined, stable populations throughout the world are considered to be important adjuncts in improving understanding of the biology of these disorders. In this respect, collaboration between centres in de- veloping and developed countries is recommended, where appropriate. 11. To achieve optimal rates of advance in under- standing CMP and its control, researchers working in specialized centres at the forefront of their fields should be recruited as participants or consultants in investigations. Expertise is needed especially in cellular and molecular biology, immunology, and virology; and, to this end, interdisciplinary work- shops may be useful. 12. In order to disseminate knowledge about CMP more widely and to facilitate early recognition of the disease, teaching seminars and the establishment of travelling fellowships are highly recommended. The development of illustrated teaching materials for wide dissemination by WHO is also recommended. 13. Review of the status of the field at regular in- tervals, for purposes of updating, is recommended. * * * W. Abelmann, Harvard Medical School, Beth Israel Hospital, Division of Cardiology, Boston, MA, USA (Rapporteur) D. Amorim, Council on Cardiomyopathies, Rio de Janeiro, Brazil (Chairman) M. L. Bhatia, Department of Cardiology, All-India Institute of Medical Sciences, New Delhi, India Chen Hao-zhu, Shanghai Cardiovascular Disease Institute, Shanghai, China A. 0. Falase, Department of Medicine, University College Hospital, Ibadan, Nigeria T. Hardarson, Internal Medicine, Landsspilahinn, Reykjavik, Iceland I. E. 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New York, Springer, 1980, pp. 13-19. 47. BILLINGHAM, M. E. Er AL. Myocarditis pathology panel, Texas, March 1984. Annex I Check sheet for a point system for the diagnosis of cardiomyopathy 1. General Section Name Age Sex Place of residence Place of birth History ofupper respiratory infection (if yes, state when) YesNo Family history Yes No Alchohol intake 0 1 2 3 Dyspnoea 0 1 2 3 Palpitation 0 1 2 3 Chest pain 0 1 2 3 Swelling of ankles/abdomen 0 1 2 3 Evidence of embolism Yes No Cardiomegaly 0 1 2 3 Heart sound Normal Abnormal Heart murmurs (resting) (if yes, specify) Yes No Heart size (X-ray) 0 1 2 3 ECG (if abnormal, specify) Normal Abnormal Rhythm Normal Abnormal Conduction defects (if yes, specify) Yes No Evidence of ventricular hypertrophy R L Bilateral Evidence of myocardial damage Yes No Blood film: Total white cell count Eosinophils % Degranulated eosinophils % MEMORANDUM Serology (TC) Echocardiography If abnormal: Ventricular hypertrophy Symmetric F] Asymmetric D Ventricular dilatation Ventricular dysfunction Valve function Endocardial thickening Filling defect Pericardial effusion Yes No Normal Abnormal 0 1 2 3 0 1 2 0 1 2 Normal Yes Yes Yes 2. Special studies Cardiac catheterization If abnormal: Ventricular dysfunction Pressure gradient If yes: Resting Provoked Angiography: Ventricular size Ventricular contractility If abnormal: Global Regional Filling defect Valvular insufficiency Apical aneurysm Coronary arteriography If abnormal: Endomyocardial biopsy 3 3 Abnormal No No No Normal Abnormal Yes Yes Yes Yes 0 1 2 Normal Yes Yes Yes Yes Yes Normal 0 1 2 Yes No No No No 3 Abnormal No No No No No Abnormal 3 No Note: 1. In centres where additional studies are desirable and can be performed, they may be added. Examples include viral studies, serological tests for Trypanosoma cruzi, exercise studies, ambulatory ECG monitor- ing, and endomyocardial biopsy. 2. The establishment of definitions for each item on the checklist is obligatory. Some centres may prefer to use numerical data rather than semi-quantitative categories. The relative weights (points) to be assigned to individual items will be determined after initial testing. 374