ANNUAL REVIEWS
Annu. Rev. Med. 1990.41:75-83. Downloaded from www.annualreviews.org Access provided by University of California - San Francisco UCSF on 02/03/15. For personal use only.
Annu. Rev. Med. 1990. 41:75-83 Copyright © 1990 by Annual Reviews Inc. All rights reserved
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MANAGEMENT OF HYPERTROPHIC CARDIOMYOPATHY Rudiger Hop/, M.D., and Martin Kaltenbach, M.D.
Abteilung fUr Kardiologie, Zentrum der Inneren Medizin, Klinikum der Johann Wolfgang Goethe-Universitat, D-6000 Frankfurt am Main 70, West Germany KEY
WORDS:
beta blockers, calcium antagonists, antiarrhythmic drugs, surgical management, prognosis.
ABSTRACT
Therapy of hypertrophic cardiomyopathy aspires to reduce symptoms, increase exercise tolerance, retard or prevent disease progression, and improve prognosis. Medical treatment with calcium antagonists and suppression of rhythm disturbances with amiodarone seem to be most effective. In patients who show no improvement, surgical treatment must be considered. DEFINITION AND CLINICAL COURSE
First described as diffuse hyperplasia of the heart muscle, and later known to be the cause of sudden death during physical activity, hypertrophic cardiomyopathy (HCM) is now defined by (a) hypertrophy (or is it hyper plasia?) of myocardial fibers, sometimes associated with fiber disarray; (b) impaired diastolic filling of the left ventricle; (c) normal or supernormal left ventricular function; and (d) dynamic obstruction of the outflow tract in the obstructive form (HOCM). The natural history of HCM is usually characterized by slow pro gression. Congestive heart failure due to mitral insufficiency or lm75 0066-4219/90/0401-0075$02.00
76
HOPF & KALTENBACH
paired left ventricular filling may occur without considerable fibrosis of the myocardium. Sudden death can be observed independently of objective findings and symptomatic status. Annual mortality is more than 3.5% in untreated patients (1).
Annu. Rev. Med. 1990.41:75-83. Downloaded from www.annualreviews.org Access provided by University of California - San Francisco UCSF on 02/03/15. For personal use only.
MEDICAL TREATMENT Therapy with Beta-Adrenergic Blocking Agents
Acute administration of beta blockers may counteract supernormal con tractility at rest and may reduce the augmentation of outflow tract gradient in HOCM caused by positive inotropy. Beta blockers can improve exercise tolerance by reducing heart rate and by negative inotropy. A reduction of the basal gradient in HOCM is seldom observed, but the increase with sympathetic stimulation can be prevented, and widening of the effective outflow orifice can be observed. Because of negative inotropy, left ven tricular end diastolic and end systolic volume increases and ejection fraction decreases, with cardiac output remaining unchanged (2, 3). On the other hand, there is no beneficial influence on ventricular diastolic function, and the filling pressure increased both at rest and during exercise (4). During long-term treatment, beta blockers can relieve typical symptoms such as dyspnea and angina, but in only a few cases do they reduce fre quency of lightheadedness or syncope. Also, exercise tolerance is improved in only some patients (5). Long-term observations reveal symptomatic benefit on occasion, but more often, symptoms remain unaffected or they reappear (6). In addition, the favorable hemodynamic effects are not repro duced during long-term oral therapy (7). The overall clinical course is not influenced, and mortality rate remains high (8). Better results were reported following high oral doses of 500 mg of propranolol per day (9). However, in our own experience with 480 mg of propranolol per day, we found no influence on symptoms, Sokolow index, heart size, or echocardiographic measurements (10). Therapy with Calcium Antagonists
The importance of the calcium ion in the pathogenesis of myocardial hypertrophy, its role in myocardial contraction and relaxation, and the evidence of calcium antagonist receptors in the atrial tissue (II) all argue for therapy with calcium antagonists. In 1976 we described our first results with verapamil: Patients reported impressive relief of symptoms, attended by objective improvement (12). Following intravenously administered verapamil, outflow obstruction decreased. After oral administration, exer-
Annu. Rev. Med. 1990.41:75-83. Downloaded from www.annualreviews.org Access provided by University of California - San Francisco UCSF on 02/03/15. For personal use only.
HYPERTROPHIC CARDIOMYOPATHY
77
cise capacity and symptomatic status improved in comparison to placebo and propranolol (13). Echocardiography ( 14), radionuclide angiograms ( 15), and hemodynamic investigations (10) verified the improvement of left ventricular relaxation and filling brought about by acute and chronic verapamil or by nifedipine administration. Our clinical experience includes 101 consecutive patients with HeM treated with calcium antagonists (Table 1). Most patients complained of typical symptoms, in particular, dyspnea and angina pectoris. Only 10 patients were symptom-free. During therapy, 85% of the previously symp tomatic patients reported improvement or complete relief of symptoms.
1 Data on 101 patients with proven hypertrophic cardiomyopathy and treated with calcium antagonists
Table
female: 21:
age: 43 ± 11.8
male: 80:
(12 - 61
Annu. Rev. Med. 1990.41:75-83. Downloaded from www.annualreviews.org Access provided by University of California - San Francisco UCSF on 02/03/15. For personal use only.
Annu. Rev. Med. 1990. 41:75-83 Copyright © 1990 by Annual Reviews Inc. All rights reserved
Further
Quick links to online content
MANAGEMENT OF HYPERTROPHIC CARDIOMYOPATHY Rudiger Hop/, M.D., and Martin Kaltenbach, M.D.
Abteilung fUr Kardiologie, Zentrum der Inneren Medizin, Klinikum der Johann Wolfgang Goethe-Universitat, D-6000 Frankfurt am Main 70, West Germany KEY
WORDS:
beta blockers, calcium antagonists, antiarrhythmic drugs, surgical management, prognosis.
ABSTRACT
Therapy of hypertrophic cardiomyopathy aspires to reduce symptoms, increase exercise tolerance, retard or prevent disease progression, and improve prognosis. Medical treatment with calcium antagonists and suppression of rhythm disturbances with amiodarone seem to be most effective. In patients who show no improvement, surgical treatment must be considered. DEFINITION AND CLINICAL COURSE
First described as diffuse hyperplasia of the heart muscle, and later known to be the cause of sudden death during physical activity, hypertrophic cardiomyopathy (HCM) is now defined by (a) hypertrophy (or is it hyper plasia?) of myocardial fibers, sometimes associated with fiber disarray; (b) impaired diastolic filling of the left ventricle; (c) normal or supernormal left ventricular function; and (d) dynamic obstruction of the outflow tract in the obstructive form (HOCM). The natural history of HCM is usually characterized by slow pro gression. Congestive heart failure due to mitral insufficiency or lm75 0066-4219/90/0401-0075$02.00
76
HOPF & KALTENBACH
paired left ventricular filling may occur without considerable fibrosis of the myocardium. Sudden death can be observed independently of objective findings and symptomatic status. Annual mortality is more than 3.5% in untreated patients (1).
Annu. Rev. Med. 1990.41:75-83. Downloaded from www.annualreviews.org Access provided by University of California - San Francisco UCSF on 02/03/15. For personal use only.
MEDICAL TREATMENT Therapy with Beta-Adrenergic Blocking Agents
Acute administration of beta blockers may counteract supernormal con tractility at rest and may reduce the augmentation of outflow tract gradient in HOCM caused by positive inotropy. Beta blockers can improve exercise tolerance by reducing heart rate and by negative inotropy. A reduction of the basal gradient in HOCM is seldom observed, but the increase with sympathetic stimulation can be prevented, and widening of the effective outflow orifice can be observed. Because of negative inotropy, left ven tricular end diastolic and end systolic volume increases and ejection fraction decreases, with cardiac output remaining unchanged (2, 3). On the other hand, there is no beneficial influence on ventricular diastolic function, and the filling pressure increased both at rest and during exercise (4). During long-term treatment, beta blockers can relieve typical symptoms such as dyspnea and angina, but in only a few cases do they reduce fre quency of lightheadedness or syncope. Also, exercise tolerance is improved in only some patients (5). Long-term observations reveal symptomatic benefit on occasion, but more often, symptoms remain unaffected or they reappear (6). In addition, the favorable hemodynamic effects are not repro duced during long-term oral therapy (7). The overall clinical course is not influenced, and mortality rate remains high (8). Better results were reported following high oral doses of 500 mg of propranolol per day (9). However, in our own experience with 480 mg of propranolol per day, we found no influence on symptoms, Sokolow index, heart size, or echocardiographic measurements (10). Therapy with Calcium Antagonists
The importance of the calcium ion in the pathogenesis of myocardial hypertrophy, its role in myocardial contraction and relaxation, and the evidence of calcium antagonist receptors in the atrial tissue (II) all argue for therapy with calcium antagonists. In 1976 we described our first results with verapamil: Patients reported impressive relief of symptoms, attended by objective improvement (12). Following intravenously administered verapamil, outflow obstruction decreased. After oral administration, exer-
Annu. Rev. Med. 1990.41:75-83. Downloaded from www.annualreviews.org Access provided by University of California - San Francisco UCSF on 02/03/15. For personal use only.
HYPERTROPHIC CARDIOMYOPATHY
77
cise capacity and symptomatic status improved in comparison to placebo and propranolol (13). Echocardiography ( 14), radionuclide angiograms ( 15), and hemodynamic investigations (10) verified the improvement of left ventricular relaxation and filling brought about by acute and chronic verapamil or by nifedipine administration. Our clinical experience includes 101 consecutive patients with HeM treated with calcium antagonists (Table 1). Most patients complained of typical symptoms, in particular, dyspnea and angina pectoris. Only 10 patients were symptom-free. During therapy, 85% of the previously symp tomatic patients reported improvement or complete relief of symptoms.
1 Data on 101 patients with proven hypertrophic cardiomyopathy and treated with calcium antagonists
Table
female: 21:
age: 43 ± 11.8
male: 80:
(12 - 61
