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At cardiac catheterization, the effect of isoproterenol on coronary blood flow was compared in six patients with primary myocardial disease and six patients who appeared to have no cardiac disease. Coronary blood flow was measured by selective coronary artery injection of xenon-133 and external monitoring of disappearance curves with a dual probe, digital scintillation counter. In the presence of similar changes in cardiac output and heart rate-systolic pressure product, changes in coronary blood flow and coronary resistance in response to isoproterenol were significantly less ( P < 0.05) in the subjects with primary myocardial disease than in the normal subjects.

Previous studies in this laboratory had shown that while ethanol at levels of 200 to 300 mg 100 ml had no effect on cardiac protein synthesis, acetaldehyde ( 3.5 mg 100 ml or 0.8 m m ) markedly inhibited cardiac protein synthesis in the intact heart in vitro. In order to localize further the action of acetaldehyde and to separate the protein synthetic effects from contractile function, studies on cell free systems with cardiac muscle microsomes were carried out at concentrations of acetaldehyde seen in humans after moderate ethanol ingestion. There was a significant reduction of microsomal protein synthesis even at these levels of acetaldehyde. Thus, with an acetaldehyde concentration of 0.53 mg 100 ml (0.12 m m ) the protein synthesis was reduced to 52 ± 5.3% of the control microsomes. With acetaldehyde concentrations of 0.13 to 0.26 mg 100 ml (0.03 to 0.06 m m ), the microsomal protein synthesis was 65 ± 8.6% of the controls. The differences from the controls were statistically significant. These data show that at concentrations seen in humans following ethanol ingestion, acetaldehyde interferes with normal cardiac protein synthesis independent of contractile action and thus may play a role in the ultimate development of ethanolic cardiomyopathy.

ABSRACT The surgical correction of a case of fibromuscular subaortic stenosis in an Alsatian dog is described.

Repeated electrical stimulation of the brain stem including the hypothalamus, pons and medulla in monkeys produced an increase in arterial blood pressure, cardiac arrhythmias, various degrees of S-T segment or T wave changes and structural damage to the myocardium. The following ultrastructural changes in the myocardium occurred: distension of sarcoplasmic reticulum, swelling of mitochondria, disarrangement of filamentous arrays, formation of contraction bands, dissociation of intercalated discs and focal necrosis. These changes are similar to those found in ischemic myocardial tissue and myocardial necrosis induced by catecholamines. The myocardial lesions are probably related to activation of the sympathetic mechanism in the brain stem.

The term "reversed pulsus paradoxus" may be used to describe an inspiratory rise of the arterial systolic and diastolic pressures, presumably related to an inspiratory increase in left ventricular stroke output. We have observed a reversed pulsus paradoxus in three unrelated clinical circumstances: idiopathic hypertrophic subaortic stenosis, isorhythmic ventricular rhythms and during intermittent inspiratory positive-pressure breathing in the presence of left ventricular failure. These unusual respiration-related fluctuations of blood pressure must be differentiated from the usual pulsus paradoxus of cardiac tamponade. (N Engl J Med 289:1272–1275, 1973)

Sodium nitroprusside infused in 18 patients with intractable heart failure (nine with ischemic heart disease and nine with cardiomyopathy) produced a prompt reduction of left ventricular filling pressure (pulmonary wedge or left ventricular end-diastolic pressure) from an average of 32.2 to 17.2 mm Hg and a rise in cardiac output from an average of 2.98 to 5.2 liters per minute. Mean arterial pressure fell by 15 mm Hg, and heart rate was slightly but significantly slowed. Stroke volume and forward ejection fraction were nearly doubled. Responses were similar in ischemic heart disease and cardiomyopathy. A diuresis and natriuresis accompanied the infusion, and the clinical response was sustained in five patients in whom the drug was continued for 24 to 72 hours. These results suggest that intractable heart failure may be effectively treated by reduction in impedance to left ventricular ejection. (N Engl J Med 291:587–592, 1974)

In a hereditary cardiomyopathy of the Syrian hamster, changes in water and electrolyte metabolism were investigated. Four age groups were differentiated histopathologically. Body weight of cardiomyopathic animals was initially decreased but later exceeded that of controls. The total extracellular fluid volume was larger than in controls, with a decreased haematocrit; these changes were especially pronounced in the oldest hamsters. The myocardial extracellular space and water content underwent similar changes to those in total extracellular volume. Besides a tendency to hyponatraemia there were no alterations of the serum potassium and sodium levels in the youngest three groups. However, in animals with congestive heart failure, serum potassium was decreased and serum sodium increased. Initially serum calcium was increased and the magnesium value was normal. In prenecrotic tissue myocardial magnesium was markedly decreased but calcium only slightly increased. In the necrotizing myocardium, however, calcium was greatly elevated; in the later stages, calcium tended to decrease. Surprisingly, magnesium was unchanged in necrotizing tissue, and decreased later. Myocardial sodium and potassium did not exhibit changes during the prenecrotic but in the following stages, when potassium was lowered and sodium was elevated. A distinct rise of the extracellular sodium concentration was observed in animals with obvious congestive heart failure. Disturbed myocardial calcium and magnesium metabolism is restricted to cardiomyopathic cells and is thought to play an essential role in the necrotic process. Succeeding changes, especially in sodium and potassium, are thought to occur in myocardial cells developmentally normal but subjected to a sustained volume overload. Secondary aldosteronism is believed to be the cause for the terminal fluid and electrolyte changes in serum and myocardium.

Two siblings with Sandhoff's disease manifested clinical and laboratory evidence of significant cardiomyopathy. Postmortem examination of the hearts of both patients revealed anatomic, biochemical and ultrastructural abnormalities resulting from deficient activities of the enzymes hexosaminidase A and B. A study of the biochemical and ultrastructural changes in the hearts revealed the accumulation of the glycosphingolipid globoside in all cardiac tissues. The necropsy findings indicate that Sandhoff's disease should be considered in the differential diagnosis in infants with cardiomyopathy or mitral insufficiency.

Echocardiographic study was done on four pediatric patients with coexisting hypertrophic subaortic stenosis (HSS) and fixed left ventricular outflow (LVO) obstruction. One had valvar aortic stenosis, two had discrete subaortic stenosis and one had coarctation of the aorta. Preoperatively, HSS was not suspected in any of these patients because of the classical findings of fixed LVO obstruction. The echocardiographic examination revealed an abnormal systolic anterior movement (SAM) of the anterior mitral leaflet with ventricular septal hypertrophy in all, but these findings were overlooked or thought to be related to a subvalvar diaphragm. One or two years after the surgical removal of their fixed obstruction, all showed clinical pictures of HSS. Postoperative echocardiographic examination showed an abnormal SAM with asymmetrical septal hypertrophy, and cardiac catheterization revealed mild to severe degrees of resting pressure gradients across LVO tracts. Amyl nitrite inhalation produced a more prominent SAM with increasing pressure gradient, and angiotensin infusion abolished the SAM and reduced the pressure gradient. From our present study, echocardiography has the potential for identification of HSS coexisting with a fixed LVO obstruction. We recommend that all patients with LVO obstruction have an echocardiographic examination along with pharmacological testing. The demonstration of an unusually thickened ventricular septum and especially, abnormal SAM of the mitral valve would require careful evaluation of left heart hemodynamics and the determination of the level of the major obstruction during cardiac catheterization for pre and postoperative management.

Twenty six patients with systolic clicks, murmurs, and prolapsed mitral valve leaflets were studied because of distressing chest pain or troublesome arrhythmias. Cardiac catheterization revealed normal coronary arteries and a high incidence of left ventricular (LV) dysfunction. The patients, 20 of whom were women, averaged 41 years of age. Thirteen of the 22 patients experienced chest pain of sufficient severity to warrant hospital admission for suspected acute myocardial infarction. Twenty of 26 had abnormal ECG patterns including sinus bradycardia, 1°, 2°, and 3° block, atrial and ventricular arrhythmias and abnormal ST-T wave vectors. Three had patterns of healed transmural infarctions and five of 16 had positive exercise tests. LV dysfunction was hemodynamically documented in 20 patients by either elevated LV end diastolic pressure, low resting cardiac index, or inappropriate rise in cardiac index during exercise. In the remaining six, impaired LV dynamics were demonstrated angiographically. Left ventriculography revealed mitral valve prolapse in all patients, mitral regurgitation in 20, and mild to severe LV hypertrophy in 14 patients. Contractility, determined angiographically, was markedly impaired in 13 patients with marked hypokinesis of the antero-lateral wall of the LV resulting in the appearance of an unusual prominent convexity in this portion of the ventricle in end systole and early diastole. Seven others had similar but less severe impairment of LV contractility. These results indicate that LV dysfunction, possibly related to a primary myocardial disorder, is a significant component of the syndrome of prolapsed mitral valve leaflet. The findings in the symptomatic patients described in this study cannot be generalized to all patients with this syndrome as our sample excluded patients with mild asymptomatic forms of the disease.

The high serum activities of the enzymes creatine kinase, “α-hydroxybutyrate dehydrogenase” and aspartate aminotransf erase found in 75 patients with accidental hypothermia and 18 with hypothermic myxoedema have been shown to be unrelated to either the severity or the duration of the hypothermia, but to be directly related to disturbances of acid—base equilibrium, hypoxia and hypotension. An inverse relationship also exists between the “α-hydroxybutyrate dehy drogenase’d and the serum protein bound iodine levels, suggesting that a thyroid hormone-lack cardiomyopathy may be contributing to the exceptionally poor prognosis of those with hypothermic myxoedema. These findings have important implications for the rational management of patients with accidental hypothermia or hypothermic myxoedema.

The concept of "normalized velocity" has been applied in this study to the echocardiographic (echo) assessment of left ventricular (LV) function in 87 patients. The following normalized velocities were calculated from the ultrasound recording of LV wall motion: 1) the mean circumferential fiber shortening rate (mean V CF ), 2) the mean normalized posterior wall velocity (V PW ), and 3) the mean normalized interventricular septal velocity (V IVS ). Systolic ejection fraction (SEF), and mean (non-normalized) posterior wall velocity (PWV) were also determined. There were 19 patients with normal LV function, 5 with atrial septal defect (mean V CF , V IVS and SEF were not calculated in these patients), 16 with LV volume overload, 29 with myocardial disease, 6 with hypertrophic cardiomyopathy and 12 with coronary artery disease (CAD). Single plane cineangiographic (angio) determinations of mean V CF and SEF were obtained in 50 of the 87 patients (including all 12 patients with CAD). Mean V CF and SEF done by echo correlated very well with mean V CF and SEF done by angio in the patients without CAD ( r = 0.94 and 0.91, respectively). Mean V CF (by echo or by angio) adequately separated normal from abnormal LV function. Although correlation between mean V CF and SEF was good, mean V CF was reduced while SEF was well preserved in several patients. In spite of LV asynergy, most of the patients with CAD had good correlation between echo and angio measurements of mean V CF and SEF. Although PWV correlated with echo and angio mean V CF in the patients without CAD, the overlap of normal and abnormal values made PWV an unreliable index of LV function. In contrast, V PW proved to be a reliable indicator of LV performance in patients without LV asynergy. Agreement between V PW and mean V CF (by echo or angio) was seen in 94% of the patients; in the presence of CAD, however, greater discrepancy was seen between these two measurements. Agreement between V IVS and V PW was present in 90% of the patients without CAD, but in only 58% of the patients with CAD. The analysis of LV wall motion by echocardiography utilizing the "normalized velocity" concept appears to be a rational and practical method for evaluation of LV performance. In the absence of asynergy, V PW provides a reliable index of LV performance which may be of particular value when abnormal septal motion precludes the determination of SEF and mean V CF . In the presence of asynergy, however, mean V CF , V PW and V IVS may reflect only the performance of the visualized segment of myocardium.

A case of left atrial myxoma masquerading as a cardiomyopathy is presented; the unsuspected tumor was diagnosed by stop-action cardiac ultrasonography and echocardiography. The stop-action technique complements standard echocardiography by enhancing the delineation of anatomic and spatial orientation. It has previously been applied to congenital cardiac lesions and should prove to be a valuable noninvasive technique in the precatheterization evaluation of acquired heart disease as well.

Echocardiography provides a reliable, sensitive and practical noninvasive means for the accurate diagnosis of idiopathic hypertrophic subaortic stenosis (IHSS) and the sequential assessment of severity of left ventricular outflow obstruction in the management of this condition. The principal echocardiographic features of IHSS have been demonstrated to include: (1) anterior displacement of the anterior mitral valve in midejection; (2) asymmetric ventricular septal hypertrophy; (3) anterior position of the mitral valve at the onset of systole; (4) forward systolic movement of the posterior mitral leaflet; (5) reduced rate of anterior mitral valve closure in diastole; and (6) partial closure of the aortic leaflets in midejection. The characteristic abnormalities of anterior systolic leaflet motion observed on mitral valve echogram and the response of the leaflet to provocative maneuvers and surgical treatment strongly support the importance of the role of obstruction in IHSS and the apposition of the anterior mitral leaflet, with the hypertrophied ventricular septum as the site of subaortic stenosis.

The ground endosperm of the seeds of Cassia occidentalis (coffee senna) administered to rabbits, orally, 0.25-3.0% body weight, produced a fatal cardiomyopathy characterized by mitochondrial degeneration, lipid accumulation, myofibrillar degeneration, myocytolysis and relatively minor reparative changes. Mitochondrial damage is probably the primary morphologic lesion and results from the specific action of the toxic principle(s) of coffee senna. The other changes reflect the disordered metabolism caused by the altered function of the damaged mitochondria. The microscopic lesions in the hearts of poisoned rabbits resembled those in cattle poisoned with coffee senna and thus the rabbit is considered a useful model for the study of the intoxication. The microscopic appearances of coffee senna poisoning in rabbits and cobalt toxicity in the rat are similar.

Using the recipient's human heart removed at cardiac transplantation, the distribution of digoxin at both the cellular and subcellular level has been studied. In the presence of diffuse histological myocardial abnormalities tissue digoxin is decreased, but the subcellular distribution, presumably reflecting binding to a possible receptor site, is uniform. When the histological abnormality is focal then digoxin distribution is uniform.These results suggest that in the presence of myocardial ischaemia plasma digoxin concentrations may not reflect total myocardial levels accurately.

Summary: Although congenital heart disease is often associated with hereditary factors1,2,3, subvalvular membranous aortic stenosis has previously not been reported in a family. This communication reports the occurrence of aortic subvalvular membrance in two siblings.

Two of five cases of single coronary artery had additional cardiac anomalies. A review of the literature yielded 159 cases, 41% of which had additional cardiac anomalies. The presence of a single coronary artery without other cardiac defects (59%) was usually an innocuous finding. However, a small group of 13 cases without other anomalies were associated with sudden death or cardiomyopathy in young adulthood or childhood. Hence, we think that the presence of this anomaly is of prognostic importance, and that interest in it should be maintained. ( JAMA 230:243-246, 1974)

The typical radiologic and angiocardiographic features of complete transposition of the great vessels with the aort a arising anteriorly from the anatomic and functional right vent ricle, and the pulmonary artery post eriorly from the anat omic and fun ctional left ventricle, are well known (1–6). With the rapid st rides which have taken place in the surgical correction of this anomaly, recognition of obstruction to the outflow tract of the left vent ricle has become increasingly important. A previous report dealt with the pathological findin gs in 23 specimens with this condition (7). Both valvular and subvalvular types of left vent ricular outflow tract obstruction were identified (Fig. 1). The subvalvular va riety exhibited three different appearances: (a) a fibromuscular tunnel found only with a ventricular sept al defect, (b) a fibrous ring or diaphragm found with and without a vent ricular septal defect, and (c) subvalvular muscular narrowing caused by bul ging of the ventricular septum into the cav...

There are two main patterns of cardiomyopathy in the tropical and sub-tropical parts of the world, endomyocardial fibrosis and cardiomegaly of unknown origin. Though there is still argument as to whether these are completely separate, there is increasing evidence that they are in fact different conditions. Endomyocardial fibrosis is a pancarditis with many features resembling rheumatic heart disease, and it seems likely that the pathogenesis may involve immunological mechanisms similar to those operating in the rheumatic process. The role of the parasitic conditions so commonly present in the ecological setting of EMF, e.g. malaria and filariasis, has not been determined, but they may in some way condition an immunological situation in which EMF occurs. The high serotonin content of the plantain diet has not been shown to be a significant factor in the initiation or development of endomyocardial fibrosis. Cardiomegaly of unknown origin, or primary myocardial disease, occurs throughout the tropical and sub-tropical parts of the world and is now increasingly recognized in the more temperature countries. There seems no doubt that a dilated and hypertrophied heart with slight endocardial thickening and mural thrombi can occur in association with many conditions, and that the clinical, radiological, electrocardiographic and autopsy appearances may be the same, despite differences in the associated conditions. The occurrence of cardiomegaly of unknown origin as an endemic problem in many tropical and under-developed areas suggests that in these places there may be common aetiological situations. The basic lesion in this group of conditions appears to be myocardial in situation and metabolic in nature. Alcoholic cardiomyopathies and puerperal heart disease are two fairly well defined clinical entities, and a study of these two conditions in particular may throw light on the basic metabolic processes operating in cardiomegaly of unknown origin. Recent studies have indicated an aetiological infective agent in congestive cardiomyopathy in man, and further developments in this field are awaited.

Left ventricular dimensions from routine clinical one-plane cineangiograms were combined with left ventricular pressure measurements to permit calculation of left ventricular wall stresses. The 25 patients included 12 with normal left ventricular dynamics, 6 with volume overload, 3 with outflow obstruction, and 4 with cardiomyopathy. Average stresses calculated on the basis of an ellipsoid model agreed with average values obtained from the exact solution of a thick-walled elastic ellipsoidal shell. Peak values were 150 to 625 g/cm 2 in the circular direction and 75 to 365 g/cm 2 in the longitudinal direction. A fiber-corrected stress was defined which represents a force per muscle fiber. The variation in fiber-corrected stress during the cardiac cycle may be considerably different from the variation in simple stress. The force-velocity characteristics of circular fibers for the 25 patients are presented. The data on peak wall stress overlap in the four groups of patients. Peak velocity of circumferential fiber shortening varied from 0.44 to 0.63 lengths/sec in patients with myocardial weakness and varied from 0.74 to 2.56 lengths/sec in the other patients. Contractile element velocity was determined during ventricular ejection when the rate of force change equaled zero. Contractile element velocity of shortening was 0.22 to 0.32 lengths/sec in the cardiomyopathy group and 0.50 to 1.32 lengths/sec in the other patients.

ALTHOUGH mitral regurgitation is a frequent i. finding in patients with idiopathic hypertrophic subaortic stenosis, the cause of the regurgitation has been poorly understood. This report describes an angiographic abnormality of the mitral valve in patients with this condition and offers a possible explanation for the valvular incompetence. Materials and Methods Eleven patients with hypertrophic subaortic stenosis were studied by catheterization of the left side of the heart. The diagnosis was made in each by ventricular angiography and by recognition of the classic pressure abnormalities that have been summarized elsewhere.1 The latter included the presence of a systolic pressure gradient . . .

Hypertrophic cardiomyopathy usually involves the left ventricle more severely than the right, and when asymmetrical may produce the syndrome of idiopathic subaortic stenosis. Less commonly, clinical manifestations of inflow-tract obstruction predominate and produce a syndrome that may be mistaken for mitral stenosis, principally because of an apical diastolic rumbling murmur. The probability of this diagnostic error and the risk of a consequent unnecessary operation can be reduced by appreciating the significance of the clues to left ventricular disease revealed by the electrocardiogram and the chest roentgenogram. Furthermore, proper timing of the heart sounds differentiates the protodiastolic filling sound of cardiomyopathy from the opening snap of mitral stenosis. The correct diagnosis is established following ventriculographic and hemodynamic studies.

Dicrotism of the brachial pulse as seen in this laboratory is highly correlated with congestive cardiomyopathy and pericardial tamponade when these diagnoses are made on patients below the age of 40 who have a heart rate over 90 beats per minute (in regular rhythm). When not present otherwise, the phenomenon may be elicited by occlusive pressure at or just distal to the point from which it is being sensed, and under these circumstances age drops out as a major determinant of its occurrence. Observations from the previous literature as well as from this laboratory also indicate that dicrotism probably occurs with much less frequency in the presence of elevated blood pressures. Barner, Willman, and Kaiser's 20 experience during the early period following prosthetic replacement of the regurgitant aortic valve and our own with cardiomyopathy suggest that certain cardiac disease states may be more likely than others to give rise to dicrotism. There is a need for further clarification of this possibility. Such a study should include significant numbers of all types of heart disease, but it should also be done, insofar as is possible, in the presence of all those other factors known to favor dicrotism. Historically the dicrotic pulse appears to have excited the attention of clinicians of the last third of the nineteenth century as a part of the new knowledge obtained from the sphygmograph introduced by Marey in 1863. As the sphygmograph fell into disuse with the appearance of the sphygmomanometer and the string galvanometer, interest in the dicrotic pulse also waned, and it is only now, late in the resurgence of interest in pulses afforded by the introduction of modern electronic transducers, that dicrotism is again presenting itself for study. It should be recognized that many of the factors giving rise to dicrotism were known to writers of this earlier period.

Findings in 11 families with cardiomyopathy are reviewed. Of 98 persons examined, 47 were affected. Their mean age at the time of detection was 24 years (range 2 to 61 years). The diagnosis was made by exclusion. The presence of other affected members, often in 2 or 3 generations of the same family, enabled us to establish the familial character. The clinical findings included palpitations, arrhythmias, syncope and sudden death. Nine patients had intractable congestive heart failure, and 6 Stokes-Adams attacks; 4 of the 6 had implanted pacemakers. Several patients had proved or suspected hypertrophic subaortic stenosis. The electrocardiogram proved to be the best single tool for the detection of cardiomyopathy. Rhythm disturbances, left ventricular hypertrophy, intraventricular conduction defects and abnormal Q waves were frequent. The Wolff-Parkinson-White pattern was found in 4 patients. Clinically the diagnosis of mitral valve disease and myocardial infarction was often considered. The prognosis is uncertain; when first detected 28 patients were asymptomatic, and only 13 have remained asymptomatic during a follow-up period of 7 years. Ten of the 47 patients died during this period, and in the 9 who came to autopsy, no congenital, rheumatic, infectious or coronary heart disease was found. The hearts were enlarged, and histologie examination revealed diffuse fibrosis with severe hypertrophy of the muscle fibers. Of special interest were the dynamic changes in the electrocardiogram with the disappearance of the abnormal Q waves and infarctionlike patterns with advancing age, as well as appearance of left bundle branch block. Serum enzyme disturbances were detected in some families, and their possible significance is discussed. Genetically, the findings are consistent with transmission by an autosomal dominant gene with high penetrance.

Twenty patients with the late systolic murmur-non-ejection click syndrome were exercised on a treadmill with continuous monitoring of the ECG. Eight patients exhibited ectopic activity at rest; exercise increased the abnormalities in 16 during or after exercise. Ventricular ectopic beats were frequent during exercise in 7 patients, atrial fibrillation occurred in 1, while flat ST segment depression of 1 mm. or more developed in 12 of the patients. These changes associated with exercise may indicate a cardiomyopathy associated with the prolapsed valve leaflet which may be linked with the occurrence of sudden death reported in this syndrome. Exercise stress appears to unmask myocardial irritability and should be considered in all patients presenting with this syndrome. Therapy may then be prescribed for those patients developing significant arrhythmias or conduction changes.

Myocardial contractility of left ventricular papillary muscles from normal Syrian hamsters and those with hereditary cardiomyopathy has been studied. The animals were divided into five groups corresponding to different pathological stages and the mechanical parameters correlated with these stages. Developed force and d F d t corrected for cross-sectional area were depressed in all myopathic groups. However, developed force and d F d t , uncorrected for cross-sectional area, were restored to normal in the hypertrophied muscles in the myopathic animals at 220 and 320 days of age in the absence of congestive failure (i.e. without edema). In the early myolytic and healing stage and in the terminal edematous stages of the myopathy, force-velocity curves were depressed at all loads. However in hypertrophied and compensated hearts at 220 to 320 days, the force velocity curves were similar to controls when load was expressed as a fraction of P 0 . Assuming developed force to reflect the number of contractile sites in parallel, it was concluded that the number of normally active contractile sites per unit area was reduced at all stages of the disease. In the hypertrophied, compensated phase, it was postulated that the qualitative nature of these sites remain normal despite their quantitative reduction.

A series of thirteen primary tumors of the heart is reported, with emphasis upon the diagnostic features. Included are nine patients with myxomas of the left atrium, one with myxoma of the left ventricle, one with myxoma of the right atrium and two with other cardiac tumors. In patients with myxomas of the left atrium clinical findings imitated a variety of cardiac lesions; they were typical of pure mitral stenosis in three, of combined stenosis and regurgitation of the mitral valve in two and of pure mitral regurgitation in two. One patient had unexplained cardiac failure without murmurs and was thought to have cardiomyopathy. One patient had no evidence of cardiac disease but did have systemic emboli. The patient with left ventricular myxoma had features suggesting hypertrophic subaortic stenosis. The patient with right atrial myxoma had severe cyanosis and polycythemia, suggesting the cyanotic form of congenital heart disease. In the patient with right ventricular teratoma, symptoms suggested the presence of infundibular pulmonary stenosis; one patient with a left ventricular fibroma was thought to have an unusual form of congenital heart disease. The various features alleged to be characteristic of myxomas are seldom combined in a single case. Consequently the variability of the clinical features of cardiac tumors should be kept in mind; angiocardiographic examinations, capable of positively identifying such tumors, should not be omitted in any patient with valvular heart disease who shows unusual features or in those with obscure cardiac problems.

This echocardiographic study has demonstrated that the finding of systolic separation of the mitral leaflets is not specific for those patients with the late systolic clicklate systolic murmur syndrome but is also seen with ruptured chordae tendineae and in cardiomyopathy patients with mitral regurgitation. From these observations and with the help of observations of others, we have reasoned that the mitral regurgitation associated with cardiomyopathy is not due to mitral annulus dilatation but to papillary muscle dysfunction.

Venous return and therefore cardiac preload and afterload pressures were reduced by means of lower body decompression in two groups of patients. Group 1 consisted primarily of patients with valvular heart disease and Group 2 of patients with cardiomyopathy. Patients in Group 1 with mitral or aortic stenosis had invariable decreases of cardiac output values irrespective of the height of the initial filling pressures. Patients in Group 2 (with cardiomyopathy) had reduced output values except when the left heart filling pressures were about 40 mm Hg. In patients in Group 1 with nonstenotic valvular disease, cardiac output decreased when initial right and left heart filling pressures were below 8 and 25 mm Hg, respectively, but increased by a small amount when the filling pressures exceeded these values. From these results we have concluded that the cardiac output response to physical reduction of preload and afterload depends on both the type of heart disease and the height of the initial ventricular filling pressures. The small increases in cardiac output that occurred in patients with severely decompensated nonstenotic valvular disease suggested that a shallow descending limb to the cardiac function curve can occur in some types of heart disease. However, this probably resulted from changes in regurgitant fractions at the atrioventricular valves and not from an actual descending limb to a myocardial muscle function curve.

A family in which six members of three generations had cardiomyopathy is described. In two affected patients Adams-Stokes attacks developed and implantation of an artificial pacemaker was required. The mode of inheritance conformed to transmission by a dominant gene with variable expressivity and incomplete penetrance. Investigation of serum enzymes demonstrated significantly increased activity of lactic dehydrogenase, alpha hydroxybutyric dehydrogenase, aldolase, glutamic oxaloacetic transaminase and creatine phosphokinase in all the affected male subjects. In the affected female subjects, only slight deviations from normal enzyme activity were observed. Heterogeneity of the condition designated as familial cardiomyopathy is suggested by the observation that in a second family with this disorder normal serum enzyme activity was found in all subjects.

Characteristically, a patient with pheochromocytoma presents with paroxysmal or sustained hypertension and related symptoms. Occasionally the predominant manifestation of such a tumor may be congestive heart failure associated with primary myocardial disease, and hypertension may be absent. A patient with pheochromocytoma whose symptoms and clinical course related to a primary cardiomyopathy, and who remained normotensive until the final month of illness, has been presented. Mechanisms implicated in the development of primary myocardial disease by a pheochromocytoma have been reviewed. Diagnostic and therapeutic measures have been briefly outlined. The physician must be alert to the relatively rare occurrence of a pheochromocytoma in a patient who presents with a primary cardiomyopathy or unexplained congestive heart failure, since removal of the tumor allows for regression, if not cure, of the associated heart disease.

Left ventricular wall thickness and ejection fraction were found to be increased in 17 patients with either hypertrophic obstructive cardiomyopathy or organic obstruction to left heart outflow. Concentric hypertrophy appears to take place partly by inward growth, and this behaviour may be important for understanding the diseases associated with it.

Eighty-five patients with ventricular dysfunction due to coronary disease and to nonobstructive cardiomyopathy were studied by biplane angiocardiography (12/sec) to determine the extent of hypertrophy and the distinguishing features between primary myocardial and coronary disease. Patients with cardiomyopathy and equally severe dysfunction due to coronary disease had identical end-diastolic, end-systolic and stroke volume and work per square meter, stroke work per gram of ventricular mass, end-diastolic pressure, peak equatorial wall stress, ejection fraction, peak circumferential shortening velocity, peak ventricular ejection rate, peak external pump power, left ventricular mass and mass to diastolic volume ratio. Hypertrophy develops after myocardial infarction in proportion to ventricular dilatation and may result in a syndrome of massive hypertrophy, hypokinesis and congestive failure quantitatively identical to that found in primary cardiomyopathy except for etiology. Hypertrophy is associated with normalization of wall stress in both coronary and primary myocardial disease and is thus not dependent on the type of insult to the contractile mechanism.

Ten patients with ischemic cardiomyopathy and with marked cardiomegaly and “intractable” congestive heart failure were studied to determine their response to prolonged complete bed rest therapy. Ischemc cardiomyopathy is similar to other types of cardiomyopathy with severe congestive heart failure, cardiomegaly and electrocardiographic abnormalities, but is distinguished by a history of myocardial infarction or angina pectoris. The prognosis is poor since patients are subject to all the complications of cardiomyopathy, as well as to the sequelae of ischemic heart disease. A proper therapeutic approach encompasses treatment of the heart muscle disease, as well as of the ischemic basis. Management of patients with ischemic cardiomyopathy by prolonged, complete bed rest resulted in initial clinical improvement in all patients. Four patients experienced partial reduction in heart size. Two of these patients lived four and eight years, respectively, after discharge and two are presently living seven and eight months after completing bed rest therapy.

The incidence of toxoplasma antibodies was investigated in 4 groups of Ugandans: blood donors, and patients with endomyocardial fibrosis, congestive cardiomyopathy and rheumatic heart disease. Negative results were obtained in all but one of 38 heart patients known to be under 20 years old, and positive results among adults in 15·8% of the endomyocardial fibrosis group, 34·4% of the cardiomyopathy group, and 38·7% of the rheumatic heart group. In the last 2 groups 60·9% of males and 22·5% of females were positive. Antibodies were present in 11·7% of blood donors aged 15·25.

The clinical findings in 7 Saudi Arab women with 8 episodes of postpartum cardiac failure of obscure aetiology are described. 2 patients had persistent cardiomegaly and ECG abnormalities in their follow-up period, which amounted to 16 months in one and 26 months in the other. Electrocardiographic changes were striking in the early stages of the disease in all patients, and included T wave inversion (all patients), QTc prolongation (6), high voltage (3) and electrical alternans (one). No definite aetiology could be determined. There was an association with a low socio-economic level and a failure to obtain prenatal care. There was no demonstrable clinical malnutrition.

Myofibrillar degeneration is a common form of cardiac injury observed frequently in human beings at autopsy and is produced readily in experimental animals. Administration of exogenous catecholamines such as norepinephrine or isoproterenol has been frequently used as an experimental means of inducing cardiac injury. The potential role of catecholamines in the pathogenesis of this cardiomyopathy becomes more significant with the demonstration that local can induce a similar cardiac lesion. Early, the injured myocardial cells show clumping and disorganization of the cardiac myofibrils. Later, degenerative changes in cell cytoplasm and mineralization of mitochondria are manifest. Such injured cells may either die and be removed by phagocytosis or may be repaired by synthesis of new myofibrils. In the later stages stromal condensation and fibrosis may become evident. This lesion in its acute form in humans and when sufficiently extensive can contribute to or cause death. Since repcated episodes potentially may produce myocadial fibrosis, this lesion is worthy of more serious consideration in the evaluation of human heart disease manifest by impaired cardiac function and interstitial fibrosis.

Cardiac function in clinical heart disease is governed by ventricular (1) preload, (2) contractility, (3) afterload, (4) heart rate, and (5) dyssynergy. The major types of pathophysiologic abnormalities include inotropic disturbances, systolic mechanical pressure and volume overloads and diastolic mechanical ventricular underloading. In contractility and systolic mechanical disorders, the cardiac compensatory mechanisms of (1) Frank-Starling principle, (2) ventricular hypertrophy, and (3) sympathetic nervous system furnish substantial but limited protective reserve for maintaining cardiac output. Assessment of cardiac performance by pump (hemodynamics) and muscle (isovolumic and ejection mechanics) characteristics, including measurements of inotropic indexes of contractile force and velocity properties, provides quantitative analysis of ventricular function determinants and compensatory system interactions in heart disease. Congestive heart failure is compensated when resting cardiac output is maintained at normal levels by the adaptive reserves with their deleterious early effects: dyspnea (preload rise), angina pectoris (increased mass) and tachycardia (adrenergic activity). Decompensated congestive heart failure is the inability of the heart to deliver normal basal cardiac output with attendant late symptoms of fatigue at rest and body organ failure despite maximal use of protective reserves. The compensatory responses utilized and the critical level of depressed contractility causing decompensation are dependent on the specific pathophysiologic condition. Thus, the fundamental variable in congestive heart failure is inotropic integrity of which its abnormal degree determines decompensation in chronic heart disease. Compensation can be sustained by reserve mechanisms at a lower inotropic state in cardiomyopathy than in systolic mechanical disorders in which volume overload can be compensated for at a more depressed level of contractility than pressure overload. The standard classification of clinical function in congestive heart failure is based more on early symptoms consequent to secondary adjustments (compensatory mechanisms) than on disturbances of the primary factors of decompensation: cardiac output (crucial hemodynamic variable) and contractility (the fundamental determinant).

Sixteen patients with diffuse hypertrophic subaortic stenosis have been treated surgically. Thirteen of 14 patients undergoing excision of hypertrophied muscle from the left ventricular outflow tract via left ventriculotomy or aortotomy have survived. Operation has provided excellent symptomatic relief, associated with eradication or significant reduction of the systolic pressure gradient between the left ventricle and the aorta while the patient is at rest. Operation is recommended for those patients with this disease who are experiencing significant and limiting symptoms related to obstruction of the left ventricular outflow tract.

Masses of anomalous Z-band material, the so-called nemaline bodies, have been seen in two biopsies of human myocardium. Neither patient had a clinical picture suggesting cardiomyopathy and it is likely that nemaline bodies are a non-specific feature of developing myocardial hypertrophy in man analogous to that seen in the experimental animal.

The hemodynamic effects of maximal isometric handgrip exercise were determined in 6 normal subjects, 27 patients with coronary atherosclerotic heart disease and 6 patients with idiopathic congestive cardiomyopathy. The hemodynamic responses to isometric handgrip exercise and to dynamic treadmill exercise were compared in normal subjects and patients with atherosclerotic heart disease. In normal subjects, isometric handgrip did not alter heart sounds or precordial apex pulsations, but in patients with atherosclerotic heart disease it either accentuated or evoked atrial or ventricular gallop sounds in 59 and 44 percent, respectively. In patients with atherosclerotic heart disease and those with cardiomyopathy, apical diastolic pulsations markedly increased in amplitude during isometric handgrip. In both normal subjects and patients isometric exercise produced similar responses in systolic time intervals. Isometric handgrip evoked rapid and significant increases in systolic and diastolic blood pressure and heart rate in all normal subjects and patients. The product of systolic blood pressure and heart rate/100 (modified tension-time index) was used as an index of myocardial oxygen demand. Treadmill exercise increased mean modified tension-time index in normal subjects and in patients with atherosclerotic heart disease by 215 (+244 percent) and 147 units (+150 percent), respectively. Handgrip increased mean modified tensiontime index by 52 units in both normal subjects and patients with atherosclerotic heart disease patients (+60 and +49 percent, respectively) and by 38 units (+39 percent) in patients with cardiomyopathy. Isometric handgrip exercise is a simple cardiovascular stress test, applicable at the bedside for provoking abnormal physical signs associated with decreased left ventricular compliance or dysfunction in patients with atherosclerotic heart disease or cardiomyopathy.

Two families with familial muscular subaortic stenosis have been studied. Hemodynamic data in 2 cases and the operative findings of 1 case are described. Autopsy findings of 3 cases have been presented. Clinical findings indicate at least 3 additional cases in 1 family and 5 in the other. The pedigrees of both families have been discussed. The incidence of this lesion in each family over 3 generations suggests that the defect is related to Mendelian dominant inheritance. To our knowledge, this is the first report of cases of familial heart disease compatible with transmission by a Mendelian dominant gene. The importance of differential diagnosis of this disease from other types of aortic or subaortic stenosis prior to surgery has been stressed, since no operation has been devised for this lesion. The distinguishing clinical features include the apical and lower left sternal border location of the systolic murmur, the absence of poststenotic dilatation of the ascending aorta, the absence of calcification of the aortic value, the absence of a murmur of aortic insufficiency, and the strong family history suggesting a familial trait.

Seventy-six patients with recent Coxsackie infection were reviewed. The Coxsackie virus was considered to be aetiologically significant in patients with pleurodynia, meningitis, pericarditis, cardiomyopathy and orchitis. In patients with pneumonia or with a diagnosis of ‘non-specific illness' it was difficult to assess the significance of Coxsackie virus.