366 SINGAPORE MEDICAL JOURNAL Vol. 14, No. 3. September, 1973. ENDOMYOCARDIAL IN IDIOPATHIC ; WITH REFERENCE TO ITS NATURAL HISTORY

By Tadasu Takatsu

For the past seven years we have experienced ninety- the congestive type on the right and in 10 four patients with idopathic cardiomyopathy, which cases on the left ventricle. By light microscopy the refers to subacute or chronic myocardial disease of myocardial cells in general revealed hypertrophy, oc- unknown cause, often associated with endocardial in- casionally intermingled with atrophy, degenerative volvement. After routine clinical examinations including changes, i.e. deformity of nucleus, vacuolar degenera- , endomyocardial biopsy of the tion, scarcity of myofibrils; and in some cases deposit right and/or left ventricle was performed by Sakakibara- of chemically unknown substances in the sarcoplasmic Konno's in the majority of the cases to in- space; and excessive contraction. Mild to moderate vestigate morphological changes of the myocardium. fibrosis in the interstitium and mild thickening of the Sixty-six cases were male and twenty-eight were endocardial layer were also observed. Generally speak- female. A familial appearance was observed only in ing, these features showed no great differences between four cases. The second and third decades seem to be the two types except for severe hypertrophy, i.e. mark- included much frequently in the present series, and ed increase in average diameter of the myocardial cells the majority of the cases revealed Class I and II. in cross section in the obstructive type and a tendency After Prof. Goodwin's classification our cases were to fibrosis in the congestive type. divided into two types, i.e. hypertrophic and congestive, Electronmicroscopically, the myocardial cells show- considering cardiothoracic ratio in chest X-ray, left ed scarcity of myofibrils, increase in number and de- ventricular hypertrophy in electrocardiogram, left ven- structed mitochondria, increased and dilated sarcoplas- tricular enddiastolic volume (LVEDV) and pressure mic reticulum, abundant glycogen granules, and in some (LVEDP) and ejection fraction, although a clear-cut cases well developed Golgi apparatus, appearance of classification was very difficult because of possible shift ergastoplasm, lysosomes, lipofuchsin pigment granules, of the hypertrophic type to the congestive one. The lipid droplets, dehiscence of intercalated discs, and con- hypertrophic type was observed much more frequently traction bands. There were no significant differences than the congestive one, where six cases of obstructive between the two types, although these appearances type were included in the former. varied markedly individually. Among the symptoms on admission palpitation was The morphological appearances of the found most often encountered; dyspnea, chest pain, fainting, in were not specific to the disease fatigue, , and edema were followed in that because they were also observed in other heart dis- order. There were no great differences between the two eases such as valvular disease, congenital heart disease types except for dyspnea and edema, which were more and so forth. Therefore, endomyocardial biopsy might common in the congestive type. not be of value in this aspect. However, it gave a With respect to the cardiothoracic ratio, about two decisive basis on the diagnosis of endocardial fibroel- thirds of the cases showed over 0.50, where the con- astosis, amyloidosis and so on. For instance, a high gestive type revealed an enlarged heart in much higher school boy with no symptoms and normal heart in the per cent than the hypertrophic one. chest X-ray and electrocardiogram was diagnosed by Among the electrocardiographic abnormalities left cardiac biopsy to have endocardial fibroelastosis. ventricular hypertrophy was observed most frequently; Moreover, there was a case (22 -year -old male) with- and it was noteworthy that A -V block, right bundle out symptoms whose prognosis was known to be poor branch block, ventricular extrasystoles and pathological by endomyocardial biopsy. His electrocardiogram re- Q waves were found relatively often. Extrasytoles, path- vealed a pattern of bilateral bundle branch block. Bi- ological Q waves, abnormal P, atrial fibrillation and opsied specimens of both ventricles showed diffusely right bundle branch block were observed more fre- stained or granular substances of histochemically un- quently in the congestive type. known nature filled in the sarcoplasmic space of myo- On the 3rd and 4th sounds were cardial fibers. The substances were fine fibrous struc- detected in 54.3% and 38.3%, respectively, accompanied tures electronmicroscopically, which revealed tubular by mild systolic murmurs in about 80%. There seemed appearance measuring 50 to 80 A in diameter. About no differences between the two types. a half year later there appeared recurrent Stokes - Cardiac catheterization revealed decreased cardiac Adams attacks. Although he spent normal life with im- index in about one fourth of the total cases, elevation planted electric pacemaker for further two years, he of enddiastolic pressure of the right and left ventricles expired eventually because the myocardium became in about one third, and prominent atrial kick in the unresponsive to electric stimulation. At autopsy the right and left ventricular pressure tracings in about one peculiar deposits filled the whole sarcoplasmic space third and a half, respectively. In the hyper- of all myocardial cells, which electronmicroscopically trophic type prominent atrial kick was observed more revealed many fine tubular structures besides fine fibrous frequently in the left ventricular pressure tracings than ones found at the first biopsy. in the congestive type, whereas in the latter that was With respect to the course of cardiomyopathy there present more frequently in the right ventricular pressure were some differences between hypertrophie and con- tracings. These findings suggest that forceful contract- gestive types. In the hypertrophie type the majority of ion of the left associated with decreased dia- cases were in Class I and II, in most of which the stolic compliance of the left ventricle might become course was stable or improved with exception of one weak with progress of congestive . case with sudden cardiac death. On the other hand, Endomyocardial biopsy was performed in 42 cases Class II, III and IV yielded over 90% of the conges- of the hypertrophic type on the right ventricle and in tive type, and some cases became worse during the 12 cases on the left ventricle, whereas in 23 cases of follow-up period, even with seven deaths. One expired case of the hypertrophic type was a 14 -year -old boy, who showed normal cardiac roent- ST depression in the electro- 'The Third Division, Department of Internal Medicine, Osaka Medical genogram, nonspecific College, Takatsuki, Osaka, Japan. cardiogram, and elevation of enddiastolic pressure only in the right ventricle with normal cardiac index. The SEPTEMBER, 1973 367 myocardial cells of the biopsied ventricle revealed weighed 815 g, both atriums dilated, and both ven- moderate hypertrophy with very few degenerative tricles, especially left ventricle hypertrophied. The changes. Nevertheless, he expired suddenly on a road thickness of the left ventricular wall was 2.0 to 2.5 cm a half year later. and the septum with no special thickening of the upper Among the seven deaths of the congestive type five part of the septum. The endocardium was markedly died suddenly, one of which was that with deposits thickened in many areas, which was fibroelastosis his- of peculiar degenerative substances in the myocardial tologically. The myocardium revealed marked fibrosis cells as described previously. The other four cases died with invasion of elastic fibers from the endocardium. unexpectedly on a road, during class at school or during As these findings of the myocardium and endocardium watching television. In the remaining two cases con- were much advanced as compared to those at biopsy, gestive heart failure became refractory to the treat- there might be rapid progress of the disease for one ment. It is noteworthy that four of seven cases showed year. At the same time it should be considered the QS patterns in the electrocardiogram, and that the fact that the biopsy could provide only a limited in- biopsied myocardium showed atrophic changes mixed formation of localized lesions. with hypertrophy and interstitial fibrosis in many Finally, it must be said that the biopsied cardiac cases. One of them with sudden death is as follows: specimens give a good material to investigate etiology A 16 -year -old high school boy revealed features of of the disease by histochemical and immunological pro- congestive type with enlargement of the heart and QS cedures. We maintain a viral -infection theory of the in V1-3, whereas the heart was normal in size two disease, on which Dr. Burch reported many papers. years previously and somewhat enlarged a year ago. The immunofluorescent techniques were applied to de- By endomyocardial biopsy moderate hypertrophy with termine viral antigens in the myocardium such as Cox- degenerative changes of the myocardial cells and slight sackie adeno and so forth, but only one the endocar- B, ECHO, to moderate fibrosis, but no changes in adenovirus antigen. dium were observed. Electronmicroscopical appearances case showed positive reaction for of the myocardial cells were scarcity of myofibrils, mit- As the results were not coincident with those of Dr. ochondriosis, dilatation of sarcoplasmic reticulum with Burch, experimental investigations in animals are now ergastoplasms and so forth. The symptoms of Class III going on in order to determine the reliability of our were improved to Class II, but he died suddenly during immunofluorescent technique for detection of viral an- class at school one year later. At autopsy the heart tigen in the myocardium.