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This article compares intergroup and intragroup clinical and morphologic findings in patients with ischemic cardiomyopathy (IC), idiopathic dilated cardiomyopathy (IDC), and dilated hypertrophic cardiomyopathy (HC) undergoing cardiac transplantation (CT). Few previous publications have described findings in native hearts explanted at the time of CT. The explanted heart in 92 patients having CT was examined in uniform manner with particular attention to the sizes of the ventricular cavities and the presence of and extent of ventricular scarring. Of the 92 hearts examined, 47 had IC, 35 had IDC, and 10 had dilated HC. Although considerable degrees of intragroup variation occurred, the mean degree of left ventricular dilatation was similar among the patients with IC, IDC, and dilated HC. All patients with IC had left ventricular free wall scarring more extensive than that involving the ventricular septum, but the intragroup variation in the amounts of scarring was considerable. Nine of the 10 patients with dilated HC also had ventricular wall scarring, but it was more extensive in the ventricular septum than in the left ventricular free wall and involvement of the right ventricular wall also was present. Eight (23%) of the 35 IDC patients also had grossly visible ventricular scars but they were small and only 1 of the 8 had coronary narrowing and that was not in the distribution of the scarring. Narrowing of 1 or more epicardial coronary arteries >75% in cross-sectional area by plaque was present in all 47 IC patients, in 8 of the 35 IDC patients (7 had no ventricular scars), and in none of the 10 dilated HC patients. Coronary angiography was the major clinical tool allowing separation of the IC, IDC, and HC patients. Coronary angiography did not detect narrowing in any of the 8 patients with IDC who were found to have coronary narrowing on anatomic study. Thus, among patients with IC, IDC, and dilated HC having CT, distinctive anatomic features allow separation of patients with IC, IDC, and dilated HC, but within each group considerable variation in left ventricular cavity size and extent of ventricular scarring occurs.

Cardiac transplantation is performed in some adults having cardiac conditions causing considerable cardiac dysfunction in the absence of an increase in cardiac mass.

In summary, adipose tissue in the heart may constitute up to 50% of the cardiac weight. The greater amounts of cardiac adipose tissue are associated with lower total 12-lead QRS voltages.

We examined the hearts of 366 octogenarians (184 women [50%], 264 white [72%], mean age 84 +/- 4 years). The cause of death was cardiac in 195 (53%), noncardiac but vascular in 47 (13%), and noncardiac and nonvascular in 124 patients (34%). Of the 195 patients with fatal cardiac disease, atherosclerotic coronary artery disease was the cause of death in 127 (65%): acute myocardial infarction in 87 (69%), sudden cardiac arrest outside the hospital in 19 (15%), chronic congestive heart failure with healed myocardial infarction in 15 (12%), and complications of coronary bypass surgery in 6 (4%). At least 1 of the 4 major (left main, left anterior descending, left circumflex, and right) epicardial coronary arteries was narrowed > 75% in cross-sectional area by atherosclerotic plaque in 218 patients (60%). The mean number of significantly narrowed major epicardial coronary arteries was 1.7, 1.3, and 0.7 in those who died of cardiac, peripheral vascular, or noncardiovascular causes, respectively. Among the 87 patients (33 men and 54 women) with fatal acute myocardial infarction, the women more often had ruptured ventricles (21 of 54 [39%] vs 3 of 33 [9%]), and fewer women had healed myocardial infarcts (11 of 54 [20%] vs 24 of 33 [73%], p < 0.05). Calcific deposits were present in the epicardial coronary arteries in 285 patients (78%), in the mitral annulus in 140 (38%), and in aortic valve cusps in 153 (42%).(ABSTRACT TRUNCATED AT 250 WORDS)

The mechanism responsible for sepsis-induced myocardial depression is not known. To determine if sepsis-induced myocardial depression is caused by inadequate free energy available for work, we studied myocardial energy metabolism in a canine model of sepsis. Escherichia coli-infected (n = 18) or sterile (n = 16) fibrin clots were implanted intraperitoneally into beagles. Myocardial function and structure was assessed using radionuclide ventriculograms, echocardiograms, and light and electron microscopy. The adequacy of energy metabolism was evaluated by comparing catecholamine-induced work increases [myocardial O2 consumption (MVO2) and rate pressure product (RPP)] with a simultaneously obtained estimate of intracellular free energy [phosphocreatine-to-adenosine triphosphate ratio (PCr:ATP)] determined by 31P-magnetic resonance spectroscopy. When compared with control animals, septic animals had a decrease in left ventricular ejection fraction (EF, P < 0.0001) on day 1 and fractional shortening (FS, P < 0.0003) on day 2 after clot implantation. On day 2, neither septic nor control animals had statistically significant decreases in PCr:ATP, despite catecholamine-induced increases in MVO2 and RPP (mean maximal increases in septic animals 135 +/- 31 and 51 +/- 10%, respectively). Light and electron microscopic findings showed that hearts of septic animals, compared with control animals, had a greater degree of morphological abnormalities. Thus, in a canine model of sepsis with alterations in myocyte ultrastructure and documented myocardial depression (decreased EF and FS), intracellular free energy levels (PCr:ATP) were maintained despite catecholamine-induced increases in myocardial work (increased MVO2 and RPP), suggesting high-energy synthetic capabilities are not limiting cardiac function.

Subepicardial myocardial lesions are rarely seen at necropsy, and a description of them and their causes has not been reported. Over the last 13 years we have studied 22 patients with subepicardial myocardial lesions. They ranged in age from 14 to 73 years (mean 47), and 20 were men. The lesions were associated with atherosclerotic coronary artery disease in six patients, sarcoidosis in five, idiopathic dilated cardiomyopathy in four, lymphocytic myocarditis in two, and hypoplastic right and left circumflex coronary arteries in one. In four patients the cause was unclear. In the patients with atherosclerotic coronary artery disease, the subepicardial myocardial lesions were small, few in number, and located in the left ventricular posterior wall. In patients with sarcoidosis or myocarditis, the subepicardial lesions were extensive and commonly associated with transmural left and right ventricular lesions. The right ventricular half of the ventricular septum also was frequently affected. In the remaining nine patients, the subepicardial lesions were small and unassociated with transmural left ventricular lesions. Thus subepicardial myocardial lesions occur in a variety of cardiac diseases.

The abnormality of the myocardium in hearts with hypertrophic cardiomyopathy (HC) was assessed regarding whether the muscle bundle in the mid-wall layer maintains its normal circular and continuous orientation surrounding the left ventricular (LV) cavity. Forty-seven autopsied hearts with HC were examined. The LV wall midway between the base and apex was divided into 6 segments in the transverse plane. Histologically, the circular orientation was destroyed largely or completely due to marked fascicle disarray in 77% of the anterior and posterior junctional segments. In 33% of the middle portion of the ventricular septum and in 34% of the anterior and posterior portions of the LV free wall, the midwall layer showed disarray of muscle fibers or small fascicles. In contrast, the lateral LV free wall was devoid of disarranged fibers in its midwall layer. Myocardial fibrosis usually was predominant in the portion where disarray was marked. There were deep tissue clefts often in the area of junction. In 11 hearts (7 from patients aged > 65 years), the circular unit was intact in almost every segment, as it was in 9 of 10 control hearts. The destruction of the circular unit in the area of septal-free wall junctions in most patients with HC is a previously undescribed morphologic feature of HC. This discontinuity may result from retention of an abnormal fetal myocardial architecture in which the septal latitudinal muscle was continuous with the right ventricular free wall.

The presence of numerous, abnormally arranged, cardiac muscle cells distributed widely throughout the hypertrophied left ventricular (LV) wall has been considered a characteristic, morphologic feature of patients dying of hypertrophic cardiomyopathy (HC) and also probably a determinant of impaired LV compliance. However, the relation between such regions of myocardial cell disarray and the magnitude of wall thickness in the same areas of the left ventricle has not been defined. Therefore, the present study was undertaken in which LV wall thickness and the percent area of myocardium disorganized were systematically compared in the same tissue section. No correlation was identified between wall thickness and the amount of myocardium disorganized in the same tissue sections, either when calculated separately for the ventricular septum, and anterolateral and posterior free walls, or when expressed for all 3 regions combined. Therefore, in patients with HC: (1) disorganized myocardial architecture is not confined to greatly thickened portions of the LV wall, but regions of the left ventricle with normal or only mildly increased thickness may also be disordered; and (2) whereas both LV wall thickening and cellular disorganization are manifestations of the primary cardiomyopathic process, these 2 morphologic features do not appear to be directly related with regard to their extent and distribution within the LV wall. These observations will potentially enhance understanding of the relation between LV structure and compliance in HC.

Cardiac necropsy findings are described in a 72-year-old man with Tangier disease whose plasma total cholesterol levels averaged 70 mg/dL, low-density lipoprotein cholesterol level was 45 mg/dL, and high-density lipoprotein cholesterol level was 1.4 mg/dL, and who had coronary artery bypass grafting for severe atherosclerotic coronary artery disease. At necropsy, 24 of the 72 (33%) 5-mm segments of the 4 major (right, left main, left anterior descending, and left circumflex) native coronary arteries and 4 of the 27 (15%) 5-mm segments of the saphenous vein aortocoronary bypass conduits were narrowed by more than 75% in cross-sectional area by atherosclerotic plaques. The plaques were composed primarily (91% to 97%) of fibrous tissue. Oil red O staining, polarized light microscopy, and electron microscopy revealed cholesterol deposits in the plaques and in the walls of coronary arteries, saphenous vein grafts, and aorta. Such deposits also were found in foam cells of histiocytic origin, fibroblasts in all four cardiac valves, and in Schwann cells of cardiac nerves.

Compared to patients with sudden coronary death and acute myocardial infarction, relatively little morphologic data has been reported in patients with unstable angina pectoris. This article reviews necropsy data collected from one laboratory on unstable angina pectoris. From these data, several observations are appropriate: (1) Patients with unstable angina as a group have more coronary narrowing by atherosclerotic plaque than do patients with sudden coronary death or acute or healed myocardial infarction. (2) Patients with unstable angina have a much higher frequency of severe narrowing of the left main coronary artery than do patients in other coronary subsets. (3) The coronary atherosclerotic plaques in unstable angina consist primarily of fibrous tissue, and they are more similar to those found in patients with sudden coronary death than in patients with acute myocardial infarction. (4) The frequency of acute coronary lesions (thrombi, plaque rupture, and plaque hemorrhage) is similar to that observed in patients with sudden coronary death and significantly less than that observed in acute myocardial infarction. (5) The frequency of multiluminal channels throughout the major coronary arteries is significantly higher in unstable angina compared to sudden coronary death or acute myocardial infarction. (6) The major epicardial arteries and the heart are smaller in patients with unstable angina than in patients with sudden coronary death or acute myocardial infarction. (7) The left ventricular cavity is usually of normal size in patients with unstable angina and therefore left ventricular function is usually normal.

Clinical and necropsy findings are described in 56 patients with mitral valve prolapse: 15 patients, aged 16 to 69 years (mean 39), died suddenly and mitral valve prolapse was the only cardiac condition found at necropsy (hereafter called isolated mitral valve prolapse); the remaining 41 patients had other conditions that were capable of being fatal. Of the latter 41 patients, 7, aged 17 to 59 years (mean 45), had associated congenital heart disease, and 34 patients, aged 17 to 70 years (mean 52), had no associated congenital cardiac abnormalities. Compared with the 34 patients without associated congenital heart disease and with nonmitral valve prolapse conditions capable in themselves of being fatal, the 15 patients who died suddenly with isolated mitral valve prolapse were younger (mean age 39 +/- 17 versus 52 +/- 15 years; p = 0.01), more often women (67% versus 26%; p = 0.008) and had a lower frequency of mitral regurgitation (7% versus 38%; p = 0.02). The 15 patients dying suddenly with isolated mitral valve prolapse also were less likely to have evidence of ruptured chordae tendineae (29% versus 67%; p = 0.04). The frequency of increased heart weight (67% versus 59%), a dilated mitral valve anulus (80% versus 81%), a dilated tricuspid valve anulus (17% versus 17%), an elongated anterior mitral leaflet (86% versus 54%), an elongated posterior mitral leaflet (79% versus 77%) and fibrous endocardial plaque under the posterior mitral leaflet (73% versus 63%) was similar between the two groups. The severity of the prolapse (mild 20% versus 11%; moderate 27% versus 58%; severe 53% versus 32%) also was similar between the two groups. Thus, persons with mitral valve prolapse dying suddenly without another recognized condition tend to be relatively young women without mitral regurgitation.

The hearts of 61 patients (39 men aged 64 +/- 11 years) who died from 5 hours to 42 days (median 3 days) after a fatal first acute myocardial infarction without having undergone percutaneous transluminal coronary angioplasty or coronary bypass surgery were studied to compare clinical and cardiac morphologic features of patients receiving thrombolytic therapy with tissue-plasminogen activator (t-PA) to those not receiving thrombolytic therapy. Comparison of findings in the 23 patients who received t-PA intravenously 3 +/- 1 hours after onset of symptoms, with the 38 patients who did not, showed similar baseline characteristics with respect to: age, gender, history of hypertension; location of the infarct; heart weight; severity and numbers of coronary arteries narrowed; and frequencies of plaque rupture, plaque hemorrhage and coronary thrombi. Among the patients receiving t-PA, however, there was a greater frequency of platelet-rich (fibrin-poor) thrombi in the infarct-related coronary arteries (6 of 11 vs 4 of 25 thrombi; p = 0.02), more nonocclusive than occlusive thrombi (6 of 11 vs 4 of 25 thrombi; p = 0.02), and a lower frequency of myocardial rupture (left ventricular free wall or ventricular septum) (5 of 23 [22%] vs 18 of 38 [46%]; p = 0.045).

An active, healthy, and symptom free 16 year old boy with a family history of hypertrophic cardiomyopathy died suddenly while walking home from school. Necropsy showed absence of left ventricular hypertrophy (that is, normal heart weight), though the characteristic histological abnormalities of hypertrophic cardiomyopathy, such as cardiac muscle cell disorganisation and abnormal intramural coronary arteries, were present. It is likely that this patient had hypertrophic cardiomyopathy and died before left ventricular hypertrophy developed.

The hearts of 52 patients (aged 61 +/- 11 years, 34 men) who participated in the Thrombolysis in Myocardial Infarction (TIMI) Study and died from 5 hours to 260 days (median 2.7 days) after onset of chest pain were studied. One heart became available at cardiac transplantation. Of the 52 patients, 38 received recombinant tissue plasminogen activator (rt-PA) not followed by percutaneous transluminal coronary angioplasty (PTCA) or coronary artery bypass grafting (CABG). Eight had PTCA, and 6 had CABG. The infarcts were hemorrhagic by gross inspection (with histologic confirmation) in 23 patients, nonhemorrhagic in 20, not visible grossly in 2 and, in 7, there was no myocardial necrosis by either gross or histologic examination.(ABSTRACT TRUNCATED AT 250 WORDS)

Mode of death, frequency of a healed or an acute myocardial infarct, or both, number of major epicardial coronary arteries severely narrowed by atherosclerotic plaque, and heart weight were studied at necropsy in 889 patients 30 years of age or older with fatal atherosclerotic coronary artery disease. No patient had had a coronary bypass operation or coronary angioplasty. The 889 patients were classified into four major groups and each major group was classified into two subgroups: 1) acute myocardial infarct without (306 patients) or with (119 patients) a healed myocardial infarct; 2) sudden out of hospital death without (121 patients) or with (118 patients) a healed myocardial infarct; 3) chronic congestive heart failure with a healed myocardial infarct without (137 patients) or with (33 patients) a left ventricular aneurysm; and 4) sudden in-hospital death without (20 patients) or with (35 patients) unstable angina pectoris. The mean age of the 687 men (77%) was 60 +/- 11 years, and of the 202 women (23%), 68 +/- 13 years (p = 0.0001). Although men included 77% of all patients, they made up approximately 90% of the out of hospital (nonangina) sudden death group. The frequency of systemic hypertension and angina pectoris was similar in each of the four major groups. The frequency of diabetes mellitus was least in the sudden out of hospital death group and similar in the other three major groups. The mean heart weight and the percent of patients with a heart of increased weight were highest in the chronic congestive heart failure group; values were lower and similar in the other three major groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Certain clinical and morphologic features are described in 23 patients in whom the heart at necropsy weighed at least 1,000 g (mean 1,106). The heart weight to body weight ratio ranged from 1.2 to 2.7 (normal 0.40). The 23 patients were derived from examination of the hearts of 7,671 patients with various cardiovascular disorders over a 25-year period. The massive cardiomegaly was the result of aortic regurgitation in 14 patients (61%): isolated in 8, associated with mitral regurgitation in 4, and with ventricular septal defect in 2. Three others (13%) had combined aortic valve stenosis and aortic regurgitation and 1 patient (4%) had mitral stenosis and regurgitation and mild aortic stenosis. Four patients (17%) had hypertrophic cardiomyopathy, and 1 patient (4%) had ventricular septal defect with mitral stenosis. They were 20 to 64 years old (mean 42) and 21 (91%) were men. Four patients at necropsy had 1 or more major coronary arteries narrowed more than 75% in cross-sectional area by atherosclerotic plaques, and only 4 patients had grossly visible left ventricular (LV) scars, 2 of whom had insignificant coronary narrowing. Examination of electrocardiograms in 17 of the 23 patients disclosed that Sokolow-Lyon criteria for LV hypertrophy was achieved in only 12 patients (71%) and Romhilt-Holt QRS voltage criteria faired even worse. Total 12-lead QRS voltage was more than 175 mm (10 mm = 1 mV) in 16 patients (94%) and it was more than 250 mm in 13 patients (76%). Total 12-lead QRS voltage in 17 patients ranged from 140 to 601 mm (mean 323). Measurement of the sum of the 12-lead QRS voltage may be quite useful in diagnosing LV hypertrophy by electrocardiogram.

Clinical and morphologic findings are described in two patients with congenital hypoplasia of portions of both right and left ventricular free walls in the absence of associated coronary or valvular heart disease. One, a 61 year old man who had never had clinical evidence of cardiac dysfunction, died suddenly and unexpectedly. The second, a 55 year old woman, died of progressive, eventually intractable congestive heart failure of 29 months' duration. Although at least 22 necropsy patients have previously been reported to have "parchment-like" thinning of portions of the right ventricular free wall, only one patient has previously been described with such thinning of portions of both right and left ventricular free walls. The spectrum of right or right and left ventricular wall congenital hypoplasia is a broad one, with nearly half of described patients dying of congestive heart failure in the 1st year of life and the other half reaching adulthood with or without manifestations of cardiac dysfunction.

Necropsy observations are described in 20 patients dying between October 1967 and March 1973 after replacement of the aortic valve with a Hufnagel trileaflet prosthesis. Seven patients died within two months of operation and 13, between 2.1 and 58 months (average 22). Four of seven patients dying early had extensive prosthetic thrombus causing obstruction of one coronary arterial ostium in each. Of the 12 patients surviving six months or longer after valve replacement, death in eight resulted from degeneration (tearing) of the prosthetic cusps causing severe aortic regurgitation in each, and from thrombosis of the prostheses in three, probably causing prosthetic stenosis and defintely causing narrowing of at least one coronary ostium. Thus, prosthetic degeneration or thrombosis caused death in 11 of the 12 patients surviving six months or longer. In conclusion, this trileaflet aortic prosthesis, although similar in design to the normal aortic valve, is composed of materials not durable enough to withstand the stresses created by blood flow in this position.

The subaortic fibrous "ring" in Newfoundland dogs with discrete subaortic stenosis is characterized by the presence of large, uni- and multinucleated, rounded connective tissue cells that resemble chondrocytes in several respects. Connective tissue adjacent to these cells is rich in acid mucopolysaccharides, small but cross-banded collagen fibrils, and small, poorly developed elastic fibers. The chondrocyte-like cells contain numerous cisternae of rough surfaced endoplasmic reticulum and prominent Golgi complexes, and they are surrounded by thick, concentrically arranged layers of basement membrane-like material. The differentiation of cellular and extracellular components of connective tissue in subaortic fibrous rings clearly differs in humans and in dogs with discrete subaortic stenosis.

The natural history of the cardiovascular manifestations of systemic lupus erythematosus (SLE) have been altered by corticosteroids which exert their own cardiovascular effects. This study describes clinical and necropsy observations in 36 corticosteroid-treated patients with SLE and compares them to necropsy observations in patients with SLE reported before the use of corticosteroid therapy. The 36 patients averaged 32 years of age, and 33 were women. Systemic hypertension was present in 25 (69 per cent) and left ventricular hypertrophy in 23 (64 per cent) patients. Hypertension was twice as common in the 19 patients who received this drug for more than 12 months (average 38 months) than in the 17 patients who received this drug for less than 12 months (average 6 months), and was almost five times more common among our patients than in patients with SLE in the presteroid era. Congestive cardiac failure occurred in 15 patients (43 per cent), eight times more frequent than that reported in noncorticosteroid-treated patients with SLE. Subepicardial and myocardial fat was increased in all 36 patients. Lupus carditis was similar in frequency but differed morphologically in our patients compared to those not treated with corticosteroids. Libman-Sacks-type endocardial lesions, present in 18 (50 per cent) of our patients, were smaller, fewer in number, univalvular rather than multivalvular, and mainly left-sided. Most verrucae were either partly or completely healed, and some were calcified. Pericarditis, present in 19 (53 per cent) patients, was predominantly of the fibrous type. Myocarditis was present in three patients, each of whom also had endocarditis and pericarditis. The lumen of at least one of the three major coronary arteries was narrowed more than 50 per cent by atherosclerotic plaques in 42 per cent of the 18 patients who received corticosteroids for more than 1 year, but in none of the 17 patients who received corticosteroids for less than 1 year. Four of the eight patients with narrowed coronary arteries had myocardial infarcts. Although vital to the management of SLE, corticosteroids have an over-all deleterious effect on the heart. Systemic hypertension and left ventricular hypertrophy appear or, when present, worsen; congestive cardiac failure increases; epicardial apartment of Me

Light and electron microscopic observations were made on left ventricular myocardium removed at operation from 16 patients with chronic aortic valve disease. In all 16 patients most cardiac muscle cells were hypertrophid, and surrounded by small amounts of fibrous tissue. In two of the six patients with pure aortic regurgitation and in four of the five patients with combined aortic stenosis and regurgitation, cardiac muscle cells with evidence of degeneration were present in addition to hypertrophied, nondegenerated cells. Degenerated cardiac muscle cells were not observed in the six patients with predominant aortic stenosis. Cardiac muscle cells with mild degeneration showed focal myofibrillar lysis, with preferential loss of thick myofilaments, and focal proliferation of tubules of sarcoplasmic reticulum. More severely degenerated muscle cells showed a marked decrease in the numbers of myofibrils and T tubules and proliferation of sarcoplasmic reticulum or mitochondria, or both. Severly degenerated cells usually were present in areas of marked fibrosis, often were atrophic, had thickened basement membranes and had lost their intercellular connections. These findings suggest that degenerated cardiac muscle cells have poor contractile function and may be responsible for impaired cardiac performance in some patients with chronic aortic valve disease.

Certain clinical and morphologic cardiac observations are described in 18 necropsy patients, aged 33 to 58 years (mean 45 years) (14 women), with chronic hypercalcemia (11.6 to 34.4 mg/dl [19.4]) from one to nine years (mean five years). Primary hyperparathyroidism was present in nine patients and secondary hyperparathyroidism in the other nine (of renal origin in seven). Cardiac valve anular and coronary arterial calcific deposits were present in 10 patients (Group I) including four (mean age 51 years) with considerable narrowing of two or three of the four major epicardial coronary arteries. None of the other eight patients (Group II) had cardiac valve anular or cuspal calcific deposits; only two had coronary calcific deposits, small in each, and none had significant coronary luminal narrowing. Calcium was in the media ("medial calcinosis"), with or without intimal deposition, of the coronary arteries in five patients. Comparison of the patients in Group I to those in Group II disclosed similar mean ages, durations of hypercalcemia and serum calcium levels, but significantly (p less than 0.05) higher mean total serum cholesterol levels (216 versus 163 mg/dl) and heart weights (426 versus 320 g). This study demonstrates that chronic hypercalcemia is associated with accelerated deposition of calcium in the cardiac anuli and valvular cusps, in the media and intima of the coronary arteries and in individual myocardial fibers (dystrophic calcification), and that coronary intimal calcification may be associated with or produce luminal narrowing, especially in patients with serum total cholesterol levels over 200 mg/dl. Thus, chronic hypercalcemia may be viewed as a "risk factor" to accelerated coronary atherosclerosis.

To study the changes in sulfhydryl and disulfide distribution in myocardial infarction we applied the fluorescent sulfhydryl reagent, monobromobimane to sections of myocardium from patients dying of infarction of 24 h to 7 days duration. Staining for both sulfhydryls and for disulfide after reduction of slides blocked with N-Ethyl maleimide showed that sulfhydryls were decreased in the infarcted areas. Disulfides were increased in the periphery of infarction but cells undergoing cytolysis showed loss of disulfide staining as well as sulfhydryl staining. The causes and implication of these changes are discussed.

The amount and distribution of coronary arterial narrowing by atherosclerotic plaque at necropsy is described in 70 victims, aged 22 to 81 years (mean 50), of sudden coronary death. Of 3,484 five-millimeter segments examined (mean 50 per patient) from the 4 major (left main, left anterior descending, left circumflex and right) coronary arteries, 950 (27%) were narrowed 76 to 100% in cross-sectional area (XSA), 1,127 (32%), 51 to 75%; 689 (20%), 26 to 50%; and 718 (21%), 0 to 25%. More extensive severe narrowing occurred in the proximal than in the distal halves of the left anterior descending, left circumflex and right coronary arteries. Comparison between the 31 previously symptomatic victims (angina pectoris or a clinical acute myocardial infarction or both) with the 39 victims who had previously been asymptomatic disclosed a significantly higher mean percent of severely narrowed (76 to 100% XSA) 5-mm segments (30 vs 25%, p less than 0.005) and lower mean percent of minimally narrowed (0 to 25% XSA) segments in the symptomatic group (15 vs 25%, p less than 0.001). Comparison of the 31 patients who had a healed myocardial infarction at necropsy with the 39 patients who did not disclosed a higher mean percent of 5-mm segments narrowed 76 to 100% in XSA (33 vs 24%, p less than 0.001) and a lower mean percent of segments narrowed minimally in those with a left ventricular scar (13 vs 26%, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical and morphologic features of the cardiovascular system are described in five necropsy patients with the Hurler syndrome. In all five patients the coronary arteries, four cardiac valves, mural endocardium of all four chambers, myocardial walls and aorta were affected in a characteristic manner. All of these sites contained large clear cells known as Hurler cells (readily visible by light microscopy). In addition, granular cells were observed in semi-thin (1 mu) sections and by electron microscopy in the coronary arteries, atrioventricular (A-V) valves and in myocardial interstitium. These latter cells appear to produce collagen in an abnormal way and are probably responsible for the heavy deposits of collagen in the cardiovascular system of patients with the Hurler syndrome. In the cardiac muscle cells, in smooth muscle cells of the coronary arteries and in fibroblasts, wherever located, deposits of acid mucopolysaccharides and glycolipids usually were also observed. The acid mucopolysaccharide deposits were observed easily with light microscopy except in the cardiac muscle cells where they were seen only with electron microscopy. The glycolipid depositis, observed only on examination of 1 mu thick sections or with electron microscopy, have not previously been observed in coronary arteries or in myocardial cells. The infiltration into the heart by these cells and deposits in all five patients resulted in severe narrowing of the extramural coronary arteries, considerable thickening of the cardiac valves (the left-sided more than the right-sided valves), generalized thickening of mural endocardium and "stiffening" of the myocardial walls. Thus, the cardiovascular lesions in the Hurler syndrome are specific and life-threatening.

This presentation summarizes necropsy observations in patients with three types of cardiomyopathy: idiopathic, infiltrative, and endomyocardial disease. The idiopathic variety is subdivided into two types depending on the size of the ventricular cavity. In the dilated ventricular type the left ventricular wall is frequently less than 1.5 cm. thick, intracardiac thrombi are common, the atrioventricular valve rings usually are mildly dilated, and focal myocardial and endocardial scars are common. In the nondilated type (hypertrophic cardiomyopathy), the ventricular septum is usually thicker than the left ventricular free wall, which also is thick (greater than 1.5 cm.). When the septum is similar in thickness to the left ventricular free wall (symmetric), left ventricular outflow obstruction does not occur. When the septum is thicker than the left ventricular free wall (asymmetric), left or right ventricular outflow obstruction may or may not be present. The orientation of myocardial fibers one to another in the ventricular septum in the nondilated (hypertrophic) type is abnormal, whereas it is normal in the dilated ventricular type. Intracardiac thrombi are rare and atrioventricular valve rings are never dilated in the nondilated type of idiopathic cardiomegaly. The infiltrative types of cardiomyopathies include iron, calcium, lipids, mucopolysaccharides, granulomas, amyloid, and neoplasms. The first four usually are located within myocardial cells and the latter three, between myocardial cells. It is probable that all these myocardial infiltrates are capable of producing cardiac dysfunction, primarily on a restrictive basis. Endomyocardial disease may or may not be associated with eosinophilia. When the latter occurs, the eosinophils are structurally normal. Death is related to congestive cardiac failure. This category is actuality also in idiopathic.

The relation between clinical evidence of and histologic signs of anthracycline cardiotoxicity was evaluated by reviewing the clinical and morphologic findings in 64 patients studied at necropsy, all of whom had received doxorubicin or daunorubicin chemotherapy during life. Of the 64 patients, 20 (31%) had documented clinical toxicity consisting of impaired left ventricular systolic performance; in 7 (35%) of these 20 patients, histologic signs of toxicity were absent. In the remaining 13 patients with clinical toxicity, histologic signs of toxicity ranged from mild to severe. Of the 44 (69%) patients without clinical signs of drug toxicity, 21 (48%) had no histologic sign of cardiotoxicity; in 23 (52%) of the patients without clinical toxicity, however, morphologic signs of cardiotoxicity were nevertheless present--mild in most patients, but extensive in 4. Signs of extensive histologic toxicity (19 [30%] of 64 patients) were associated with large doses (greater than 450 mg/m2) of the drug, mediastinal irradiation, and age greater than 70 years. This study suggests that attempts to monitor cardiotoxicity by serial evaluation of cardiac histology in patients undergoing anthracycline chemotherapy may be seriously limited by the fact that clinical evidence of toxicity may be present without histologic signs of toxicity; likewise, histologic signs of anthracycline toxicity may be present without clinical evidence of toxicity.

Nuclear membranes of cardiac muscle cells were studied in 134 patients with cardiac hypertrophy of various causes. Abnormalities observed consisted of: a) increased foldings and convolutions; b) nuclear pseudoinclusions formed by cytoplasmic organelles protruding into saccular invaginations of the nuclear membranes, and c) intranuclear tubules. The increased foldings and convolutions of the nuclear membranes and the nuclear pseudoinclusions appear to result from synthesis of nuclear membranes in excess of that needed to accommodate the increase in nuclear volume which occurs in hypertrophy. Intranuclear tubules were found in 6 patients and consisted of tubular invaginations, 400 to 650 A in diameter, of the inner nuclear membranes into the nucleoplasm. Some of these tubules were straight and cylindrical, and were associated with a peripheral layer of marginated chromatin; others were not associated with chromatin, appeared coiled and followed irregular courses. Intranuclear tubules in cardiac muscle cells probably represent an extreme cellular response to the stimulus of hypertrophy.

To determine the relation of a single healed myocardial infarct to a fatal acute myocardial infarct, 129 patients with 1 grossly visible healed and 1 grossly visible acute infarct were studied at necropsy. It was determined whether the acute infarct was opposite to or adjacent to the healed infarct or if 1 infarct was so large that it was both opposite to and adjacent to the other infarct. In 74 (57%) of the 129 patients, the 2 infarcts were opposite one another, in 40 (31%) they were adjacent and in 15 (12%) they were both opposite and adjacent. The age, sex, mean size of the healed infarct and heart weight were similar among the 3 groups. Acute myocardial infarcts were larger in the group that had both opposite and adjacent infarcts than either of the other 2 groups (p less than 0.001). Information regarding whether the infarcts were clinically recognized or not was available in 108 patients: both infarcts were recognized in 41 (38%), neither infarct was recognized in 15 (14%) and 1 infarct was recognized and the other was not in 52 (48%). The number of the 4 major epicardial coronary arteries narrowed at some point greater than 75% in cross-sectional area by atherosclerotic plaque was similar in patients with recognized and in those with unrecognized infarcts. Similar numbers of narrowed major epicardial coronary arteries also were found in each of the 3 infarct groups (opposite, adjacent or both).

Clinical and necropsy findings are described in 54 patients, aged 25 to 83 years (mean 53), who died within 60 days of simultaneous replacements of both mitral and aortic valves. The patients were separated into 4 groups on the basis of the presence of stenosis (with or without associated regurgitation) or pure regurgitation of each valve: 30 patients (56%) had combined mitral and aortic valve stenosis; 12 patients (22%) had mitral stenosis and pure aortic regurgitation; 8 patients (15%) had pure regurgitation of both valves; and 4 patients (7%) had pure aortic regurgitation and mitral stenosis. Necropsy examination in the 54 patients disclosed a high frequency (48%) of anatomic evidence of interference to poppet or disc movement in either the mitral or aortic valve position or both. Anatomic evidence of interference to movement of a poppet or disc in the aortic valve position was twice as common as anatomic evidence of interference to poppet or disc movement in the mitral position. Interference to poppet movement is attributable to the prosthesis's being too large for the ascending aorta or left ventricular cavity in which it resided. The ascending aorta is infrequently enlarged in patients with combined mitral and aortic valve dysfunction irrespective of whether the aortic valve is stenotic or purely regurgitant. Likewise, the left ventricular cavity is usually not dilated in patients with combined mitral and aortic valve stenosis, the most common indication for replacement of both left-sided cardiac valves. Of the 54 patients, 12 (22%) had 1 mechanical and 1 bioprosthesis inserted. It is recommended that both substitute valves should be mechanical prostheses or both should be bioprostheses.

Clinical and necropsy findings are described in eight patients who lived 20 to 31 years (mean 24 years) after healing of a transmural acute myocardial infarct. Two had left ventricular aneurysms and one had both right and left ventricular infarcts. Survival for 2 decades or more after healing of a transmural acute myocardial infarct has rarely been documented and descriptions of hearts at necropsy in patients with well-documented infarcts 20 years or more earlier are virtually nonexistent.

Certain clinical and morphologic findings are described in 55 patients whose hearts at necropsy contained so much fat that they floated in water. The patients were 47 to 89 years old (mean 67). Symptomatic coronary heart disease was present in 28 (51%) and valvular heart disease (mitral stenosis) in 3 (5%). The heart at necropsy was enlarged (greater than 350 g for women and greater than 400 g for men) in 45 patients (82%). The mean heart weight for the 31 women was 470 g and for the 24 men, 515 g. In addition to the severe increase in fat in the atrioventricular sulci and over both ventricles, the amount of fat in the atrial septum was increased in all patients. In 14 patients (25%), the thickness of the atrial septum cephaled to the fossa ovale was greater than or equal to 2 cm. Excessive fat in this location is called "lipomatous hypertrophy of the atrial septum." Of the 16 patients (29%) with fatal acute myocardial infarction, 7 (44%) had rupture of either the left ventricular free wall or ventricular septum. The high frequency of cardiac rupture in these patients supports the contention that rupture during acute myocardial infarction is more common in the fatty than in the non-fatty heart.

Certain cardiac morphologic findings are described in 16 necropsy patients having operative closure of an acquired ventricular septal defect (VSD) during acute myocardial infarction (AMI). Of the 16 patients, 6 were women (mean age 69 +/- 7 years) and 10 were men (mean age 60 +/- 11 years). The AMI associated with the VSD was the first coronary event in 13 patients (81%). At least 6 patients had a history of systemic hypertension. Conduction disturbances were diagnosed by electrocardiogram in 5 patients (31%). The median interval from the onset of the AMI to death was 11 days, and from the onset of the AMI to operative closure of the VSD, 4 days. Eight patients died in the operating room or within 2 hours of operation. Coronary artery bypass grafting was performed simultaneously with the VSD closure in 7 patients. Death was attributed to unsuccessful VSD closure in 5 patients, to inadequate left ventricular cavity after resection of necrotic myocardium in 5 patients and to inadequate viable left ventricular myocardium in 4 patients. Heart weights were increased in 14 patients (88%). The AMI associated with the VSD was anterior in 9 patients and posterior (inferior) in 7. Healed myocardial infarcts were present in 3 patients. All 16 patients had severe (greater than 75% in cross-sectional area) narrowing of 1 or more of the 4 major epicardial coronary arteries.