Walter H. Abelmann

Prevalence and etiology of idiopathic dilated cardiomyopathy (summary of a National Heart, Lung, and Blood Institute Workshop)

Idiopathic dilated cardiomyopathy (IDC) is the primary indication for cardiac transplantation, with associated costs of approximately

The Hemodynamic Response to Chronic Anemia

177 million per year. Recognizing the economic implications of IDC, the increasing incidence, and the limited information on pathogenesis and prognosis, the National Heart, Lung, and Blood Institute convened a workshop on the Prevalence and Etiology of Idiopathic Dilated Cardiomyopathy on June 13 to 14, 1991. The difficulties of studying the disease were reviewed, including its relatively low prevalence, its potentially pluricausal nature, and the fact that it is often a diagnosis of exclusion. Still, it presents significant challenges to the cardiovascular scientific community, since the mechanism of myocardial damage and related etiologic and prognostic factors are virtually unknown. The development of more reliable measures of immune-mediated damage and noninvasive measures of impaired cardiac function present new research opportunities in this disorder. Standardized diagnostic criteria for use in observational and interventional trials were developed, and priorities for future research were proposed. Population-based registries and nested case-control studies, where feasible, are appropriate study designs for tracking incidence and prevalence, and for identifying risk factors, respectively. Interventional studies should focus on secondary prevention, through modifying immune-mediated damage in clinically evident dilated cardiomyopathy, and through prevention of sudden death in patients with the disorder. Primary prevention trials must await the identification of modifiable risk factors and of appropriate and effective interventions.

The challenge of cardiomyopathy.

To determine whether the hyperkinetic circulatory response to chronic anemia is obligatory and to assess its strength and potential reversibility, the hemodynamic state at rest was assessed (indicator-dilution method) in 24 patients with chronic anemia before and after certain interventions. A comparison of cardiac output measured before and after treatment established the consistency of the hyperdynamic response to anemia. In the absence of convalescent data, this response might have been overlooked in some anemic patients whose cardiac output fell within the normal range. In the anemic state, cardiac output correlated negatively and significantly with age (r=-0.752). This relationship may account for the apparent absence of the hyperkinetic circulation in elderly, anemic patients. In only the most anemic (hemoglobin, 3.8 g/100 ml) of six patients did inhalation of 100% oxygen lower cardiac output significantly. In four patients, studied in both the supine and sitting posture, orthostatic stress was cons...

The spectrum of pure mitral stenosis. Hemodynamic studies in relation to clinical disability.

The combined clinical and pathophysiologic characteristics and diagnostic features as well as current concepts of pathogenesis, therapy and prevention of the principal forms of cardiomyopathy are reviewed. These include hypertrophic cardiomyopathy, dilated cardiomyopathy, restrictive cardiomyopathy and specific cardiac muscle disease. Emphasis is placed on recent developments and unresolved questions requiring application of newer techniques of molecular biology and genetics and adult myocyte culturing.

Myocarditis presenting as acute myocardial infarction

The pathophysiology of mitral stenosis is reassessed, with special emphasis upon relation of physiologic variables to severity of symptoms and degree of disability. Data from 44 patients with pure mitral stenosis are presented. Cathetcrization of the left side of the heart was performed in all and catheterization of the right side of the heart in 25 patients. Twenty-six patients were in Class I or II (American Heart Association Functional Classification) with mild symptoms or none at all, while 18 patients were in Class III with severe symptoms. As expected, inverse relationships existed between left atrial pressure and mitral valve area (r = − 0.618), pulmonary arterial pressure and mitral valve area (r = − 0.575), and between mean mitral diastolic pressure gradient and mitral valve area (r = − 0.708). There was a positive relationship between cardiac index and mitral valve area (r = + 0.407). All correlation coefficients were significant to the 1 per cent level. Seventeen of the 26 patients in Classes I and II had mitral valve areas of 1.5 cm2, or less. This indicates that severe mitral stenosis can be found in a nearly asymptomatic state. All of the 18 Class III patients had valve areas of less than 1.5 cm2. These two groups of patients with similar degree of valve narrowing were compared. Cardiac output was significantly (p < 0.01) reduced in both categories (2.81 L. min. M2. for Classes I and II, and 2.82 L. min. M2. for Class in patients). Left atrial pressure in the two groups, 18 and 19 mm. Hg, respectively, and mean diastolic pressure gradient, 11 and 13 mm. Hg, respectively, did not show significant differences. However, pulmonary arterial pressure, 22 mm. Hg in Classes I and II and 36 mm. Hg in Class II, as well as pulmonary arteriolar resistance, 105 compared to 425 dynes sec. cm. −5, did allow a hemodynamic distinction between the two clinically different groups. These data suggest that the degree of pulmonary vascular disease is an important determinant of the symptoms of mitral stenosis. For Class I and II patients, history, physical examination and radiographic studies did not allow an accurate prediction of the mitral valve size. It is suggested that one of the earliest adaptive mechanisms to mitral blockade is a decrease in cardiac output and that this is not mediated, initially, through an elevated pulmonary vascular resistance, myocardial failure or atrial fibrillation. It is one of the means by which a patient with severe stenosis of the mitral valve may remain asymptomatic for prolonged periods of time.

Therapy with cyclosporine in experimental murine myocarditis with encephalomyocarditis virus.

Ten patients with acute myocarditis, who were initially seen with clinical signs of acute myocardial infarction, will be discussed. All had symptoms and seven had laboratory evidence of an acute viral infection. Acute cardiac findings consisted of chest pain in nine patients, compatible ECGs and elevated creatine kinase levels in 10, positive MB fractions in eight, and regional wall motion abnormalities in eight. Acutely, the left ventricular ejection fraction was less than 55% in six patients; ventricular ectopy occurred in five patients, bundle branch block in four, transient junctional escape rhythm in three, and congestive heart failure in three. Among the nine patients followed-up for 1 to 14 months there was one death, five patients had normal results of exercise tests, and three had normal coronary angiograms. Wall motion abnormalities persisted in four patients; ejection fraction improved in five and was less than 55% in three. These findings suggest that focal myocardial damage may occur during acute viral myocarditis and mimic acute myocardial infarction resulting from atherosclerotic coronary artery disease.

The quiz electrocardiogram: a new diagnostic and research technique for evaluating the relation between emotional stress and ischemic heart disease.

To explain the progression from infectious viral myocarditis to congestive cardiomyopathy an infection/immune hypothesis has been proposed stating that the primary viral process incites an excessive or disordered immunologic response against the myocardium. To test whether one form of immunosuppressive therapy might ameliorate this process, we used cyclosporine in a murine preparation of infectious myocarditis (encephalomyocarditis [EMC] virus), which has been shown to result in a congestive cardiomyopathy pathologically similar to that seen in man. Eight-week-old male DBA-2 mice were infected with EMC virus and randomized to a treatment or control group. Cyclosporine (25 mg/kg/day) was administered subcutaneously for 3 weeks, starting (1) at 1 week after infection during viral replication, and (2) at 3 weeks after infection, after the period of active viral replication. In mice treated during viral replication there was a significantly higher mortality rate compared with that of control mice (15/21 vs 9/29, p = .01). There was no evident reduction in myocardial pathology (inflammation, necrosis, or calcification) in the treated compared with the control groups. In mice treated after the period of viral replication, there was no improvement in mortality (8/22 vs 2/19, NS) compared with control. Treated mice showed no reduction in myocardial histopathologic lesions. Furthermore, treated mice had significantly greater heart weight/body weight ratios (1.3 +/- 0.4% vs 1.0 +/- 0.3%, p less than .005), lung weight/body weight ratios (1.1 +/- 0.5% vs 0.8 +/- 0.3%, p less than .05), and liver weight/body weight ratios (6.0 +/- 0.8% vs 5.4 +/- 0.6%, p less than .005) than control mice, suggesting more severe myocardial failure.(ABSTRACT TRUNCATED AT 250 WORDS)

Correlation of serum magnesium levels and cardiac digitalis intoxication

To evaluate possible cardiovascular effects of emotional stress, a specially designed 12 minute tape-recorded stress quiz was administered to 43 subjects while blood pressure and the electrocardiogram were monitored. For the entire group, the heart rate and blood pressure rose from respective control levels of 76 beats/min and 136/87 mm Hg to a mean during the quiz of 87 beats/min and 158/94 mm Hg. This difference was highly significant. Of the 43 subjects, 33 were classified as executives and 10 as nonexecutives. There were three groups of executives: control and angina with and without a history of hypertension. Both groups of executives with angina responded with a significantly higher heart rate than that of the executive control group. Blood pressure response was significantly greater in executives with angina and hypertension than in the other groups. Heart rate and systolic blood pressure responses to the quiz were lower in nonexecutives with angina than in executives with angina. During the quiz, 10 of 14 executives with angina had S-T segment depression greater than 0.5 mm; of these, 7 evidenced greater than 1.0 mm depression, andin 3 of these the depression was greater than 1.5 mm and in 2 greater than or equal to 2.0 mm. None of the executive control subjects had S-T depression greater than 0.5 mm Among nonexecutives, 2 had S-T depression greater than 0.5 mm but none greater than 1.0 mm S-T depression. Seventeen of the patients also were given a bicycle exercise tolerance test. There was a significant correlation between S-T depression in response to exercise and to the quiz (r = 0.63; P less than 0.01). The quiz electrocardiogram is presented as a new research technique and diagnostic test for evaluating the relation of emotional stress to ischemic heart disease.

Treatment of viral myocarditis with ribavirin in an animal preparation.

Abstract A prospective study was undertaken to compare the prevalence of hypomagnesemia and hypermagnesemia in patients with cardiac digitalis toxicity and in digitalized patients without toxicity. During an 8 month period on a general medical service, there were 38 patients with “definite” or “possible” digitalis toxicity, by serial electrocardiographic studies, among 120 digitalized patients whose serum magnesium levels were obtained. Serum magnesium concentrations were measured by atomic absorption spectrometry. Hypomagnesemia was present in 21 percent of patients with and 10 percent of those without digitalis toxicity. Hypomagnesemia was not more prevalent in patients with toxicity but relatively lower serum levels of digoxin or digitoxin. The presence of hypermagnesemia was significantly greater in patients with toxicity (18 percent) than in those without toxicity (5 percent), and appeared to be related to a significantly greater prevalence of abnormal renal function in the former group. The potential value of magnesium administration in hypomagnesemic patients with cardiac digitalis toxicity warrants investigation. Caution should be exercised in the administration of magnesium sulfate to digitalis-toxic, azotemic patients who may already be hypermagnesemic.

Prevention of viral myocarditis with recombinant human leukocyte interferon α A/D in a murine model

The therapeutic effects of ribavirin, a broad-spectrum, antiviral agent, on experimental myocarditis caused by encephalomyocarditis (EMC) virus were investigated. Four-week-old DBA/2 mice were inoculated with 10 plaque-forming units (pfu) of EMC virus. Ribavirin in a dose of 100 (group 1, n = 20), 200 (group 2, n = 10), or 400 mg/kg/day (group 3, n = 10) was administered subcutaneously on days 0 to 12 after virus inoculation, and animals were observed for 12 days. Control animals were injected with saline (n = 20). Mice treated with ribavirin survived longer than controls (mean survival 6.7 days for group 1, 7.4 days for group 2, 7.7 days for group 3, and 5.2 days for control; p less than .005). Myocardial virus titers on days 6 to 8 were significantly lower in group 2 (3.24 +/- 0.49 log10pfu/mg; p less than .005) and in group 3 (1.70 +/- 0.65 log10 pfu/mg; p less than .001) compared with controls (4.09 +/- 0.57 log10 pfu/mg). The incidence of gross myocardial lesions was significantly lower in group 1 (13/20, 65%), group 2 (2/10, 20%), and group 3 (0/20, 0%) compared with controls (20/20, 100%) (p less than .05). Histologic examination showed extensive myocardial necrosis and cellular infiltration in untreated groups; there was less infiltration in groups 2 and 3 (p less than .01) and less severe necrosis in group 3 (p less than .01). Thus ribavirin effectively inhibited myocardial virus replication and reduced the inflammatory response and myocardial damage in an experimental preparation of viral myocarditis.