Hypertrophic Cardiomyopathy: The Therapeutic Role of Calcium Antagonists

343 Pages·1982·9.153 MB·English

by  J. F. Goodwin (auth.), Professor Dr. med. M. Kaltenbach, S. E. Epstein M. D. (eds.)

Hypertrophic
Cardiomyopathy
The Therapeutic Role of
Calcium Antagonists
Edited by
M.Kaltenbach and S.E.Epstein
With 172 Figures
Springer-Verlag
Berlin Heidelberg New York 1982
Professor Dr. med. M. KALTENBACH, Zentrum der Inneren Me
dizin, Abteilung flir Kardiologie, Klinikum der Johann-Wolfgang
von-Goethe-Universitat, Theodor-Stem-Kai 7, D-6000 Frank
furt 70
S. E. EpSTEIN, M. D., Cardiology Branch, National Heart, Lung,
and Blood Institute, National Institutes of Health, Bethesda,
MD 20205/USA
ISBN-13 :978-3-642-68284-1 e-ISBN-13 :978-3-642-68282-7
DOl: 10.1007/978-3-642-68282-7
Library of Congress Cataloging in Publication Data. Main entry under
title: Hypertrophic cardiomyopathy. Bibliography: p. Includes index. 1.
Heart-Hypertrophy-Chemotherapy. 2. Verapamil. 3. Calcium-Antago
nists-Therapeutic use. I. Kaltenbach, Martin. II. Epstein, S. E. (Stephen
E.) [DNLM: 1. Myocardia diseases-Drug therapy. 2. Calcium-Antago
nists and inhibitors. 3. Iproveratril-Therapeutic use. WG 280 H998]
RC685.H9H957. 616.1'24. 81-16665. ISBN-13:978-3-642-68284-1(U.S.). A
ACR2
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© by Springer-Verlag Berlin Heidelberg 1982
Softcover reprint of the hardcover 1st edition 1982
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2127/3130-543210
Preface
First described in 1907 by Schicke but recognized as a clinical entity only as recently
as 1958, when Teare published the pathologic findings in patients with hypertrophic
cardiomyopathy (HeM), an explosion of knowledge about this fascinating disease
has occurred, which has caused a profound evolution of our understanding of its
broad pathophysiologic and clinical spectrum. Progress has been particularly rapid
in the past few years when M-mode echocardiography, and more recently 2-dimen
sional echocardiography have been applied to the study ofHCM.
In addition to new insights as to what the disease is, there has been enormous
progress concerning its treatment, with the application of beta-adrenergic blocking
agents and surgical relief of left ventricular outflow tract obstruction. Although
these approaches have led to great strides in the symptomatic control of the disease,
many patients' symptoms have remained refactory to medical and surgical therapy.
Most discouragingly, sudden death still occurs, even in patients on large doses of
beta-blocking agents and in patients who have had surgical relief of left ventricular
outflow tract obstruction.
Therapy of HCM with calcium antagonists was initiated in 1973 in Frankfurt!
Main. Independently, several years later, the group in Bethesda started with the
same therapeutical approach. Many assumptions had to be made to justify this new
form of treatment, e.g.:
High doses of verapamil can be given over a long period of time without severe
side effects
- Cardiomyopathy or its clinical effects relates to calcium ion overload or in
creased intramyocardial availability of calcium
The negative inotropic action ofverapamil is not of major clinical importance.
In the meantime our understanding of the disease as well as of the basic princi-
ple of calcium antagonism as defined by Fleckenstein has considerably increased.
Most importantly, therapeutic experience with the use of verapamil in treating pa
tients with HCM has increased markedly, and data relating to its effects have been
collected at different institutions throughout the world.
This volume is aimed to represent our up-to-date knowledge of the topic. It of
fers for the first time an international overview on a new therapeutic approach to
HCM.
MARTIN KALTENBACH· STEPHEN E. EpSTEIN
Contents
Clinical and Anatomical Characterization of Hypertrophic Cardiomyopathy
Synopsis. J. F. GOODWIN . . . . . . . . . . . . . . . . . . . . .. 3
Hypertrophic Cardiomyopathy: An Overview. S. E. EpSTEIN and B. J. MARON.
With 7 Figures . . . . . . . . . . . . . . . . . . . . . . . 5
Echocardiographic Identification of Patterns of Left Ventricular Hyper-
trophy in Hypertrophic Cardiomyopathy. B. J. MARON, 1. S. GOTT-
DIENER, and S. E. EpSTEIN. With 17 Figures .......... 18
Distribution and Significance of Cardiac Muscle Cell Disorganization
in the Left Ventricle of Patients with Hypertrophic Cardiomyopathy:
Evidence of a Diffuse Cardiomyopathic Process. B. J. MARON and
W. C. ROBERTS. With 12 Figures . . . . . . . . . . . . . . . 38
Left Ventricular Biopsy in Hypertrophic Cardiomyopathy: Light and
Electron Microscopic Evaluations. B. KUNKEL, M. SCHNEIDER, R. HOPF,
G. KOBER, K. HUBNER, and M. KALTENBACH. With 3 Figures . . . .. 58
Cardiomyopathy in Animals and Therapeutic Interventions
Synopsis. B. J. MARON . . . . . . . . . . . . . . . . . . . . . .. 72
Spontaneously Occurring Hypertrophic Cardiomyopathy in Dogs and Cats:
A Potential Animal Model ofa Human Disease. B. J. MARON,
S.-K. Lm, and L. P. TILLEY. With 9 Figures ........... 73
Cardiac Effects of Nerve Growth Factor in Dogs. M. P. KAYE,
D. J. WITZKE, D. J. WELLS, and V. FUSTER. With 7 Figures 88
Prevention of Myocardial Cell Necrosis in the Syrian Hamster - Results
of Long-Term Treatment. K. LOSSNITZER, A. KONRAD, D. ZEYER,
and W. MOHR. With 4 Figures . . . . . . . . . . . . . . . . 99
Prevention by Verapamil ofIsoproterenol-Induced Hypertrophic Cardio-
myopathy in Rats. A. FLECKENSTEIN, M. FREY, and J. KEIDEL.
With 4 Figures . . . . . . . . . . . . . . . . . . . . . . .. 115
Effects of Acute Administration of Verapamil in Patients with Hypertrophic
Cardiomyopathy
Synopsis. S. E. EpSTEIN .................... 122
Acute Hemodynamic Effects ofVerapamil in Hypertrophic Cardiomyo-
pathy. D. R. ROSING, K. M. KENT, R. O. BONOW, and S. E. EpSTEIN.
With 9 Figures . . . . . . . . . . . . . . . . . . . . . . . 124
VIII Contents
Hemodynamics and Contractility After Oral, Intravenous, and Intracoronary
Application of Calcium Antagonists. W.-D. BUSSMANN, R. HOPF,
A. TROMPLER, and M. KALTENBACH. With 9 Figures ....... l38
Effect of V erapamil on Left Ventricular Isovolumic Relaxation Time and
Regional Left Ventricular Filling in Hypertrophic Cardiomyopathy.
P. HANRATH, D. G. MATHEY, P. KREMER, F. SONNTAG, and W. BLEIFELD.
With 5 Figures . . . . . . . . . . . . . . . . . . . . . . . .. 148
Treatment of Hypertrophic Cardiomyopathy with Verapamil
Synopsis. H. KUHN ................. 160
Verapamil Treatment of Hypertrophic Cardiomyopathy. R. HOPF and
M. KALTENBACH. With l3 Figures ............. 163
Volume Parameters of the Heart During Long-Term Verapamil Treatment
in Patients with Hypertrophic Cardiomyopathy. M. KALTENBACH and
R. HOPF. With 7 Figures .................. 179
Long-Term Clinical Effects ofVerapamil in Patients with Hypertrophic
Cardiomyopathy. D. R. ROSING, J. R. CONDIT, B. J. MARON,
K. M. KENT, M. B. LEON, R. O. BONOW, L. C. LIpSON, and S. E. EpSTEIN.
With 4 Figures . . . . . . . . . . . . . . . . . . . . . . . .. 187
Effects ofVerapamil on Ventricular Wall Thickness of Patients with
Hypertrophic Cardiomyopathy. H. O. HIRZEL, M. P. TROESCH, R. JENNI,
and H. P. KRAYENBUEHL. With 6 Figures ........... 203
Long-Term Verapamil Treatment in Patients with Hypertrophic
Nonobstructive Cardiomyopathy. H. KUHN, U. THELEN, C. LEUNER,
E. KOHLER, V. BLUSCHKE, and F. LOOGEN. With 10 Figures 214
Verapamil: Its Potential for Causing Serious Complications in Patients
with Hypertrophic Cardiomyopathy. S. E. EpSTEIN and D. R. ROSING.
With 3 Figures . . . . . . . . . . . . . . . . . . . . . . .. 225
Long-Term Results of Different Therapeutic Interventions in Comparison
with Verapamil
Synopsis. R. HOPF . . . . . . . . . . . . . . . . . . . . . . . 236
Efficacy of Operation for Obstructive Hypertrophic Cardiomyopathy:
A 20-Year Experience with Ventricular Septal Myotomy and Myec
tomy. B. J. MARON, J.-P. KOCH, S. E. EpSTEIN, and A. G. MORROW.
With 10 Figures . . . . . . . . . . . . . . . . . . . . . 238
Functional Results in Medically and Surgically Treated Patients with
Hypertrophic Obstructive Cardiomyopathy. B. LOSSE, H. KUHN,
and F. LOOGEN. With 3 Figures .............. 251
Long-Term Treatment of Hypertrophic Cardiomyopathy with Verapamil
or Propranolol. Preliminary Results ofa Multicenter Study. G. KOBER,
R. HOPF, A. SCHMIDT, M. KALTENBACH, G. BIAMINO, R. SCHRODER,
P. BUBENHEIMER, H. ROSKAMM, P. HANRATH, F. SONNTAG,
K.-E. v. OLSHAUSEN, H. ZEBE, W. KOBLER, W. SCHONUNG, A. MULLER,
and M. SCHLEPPER. With 3 Figures . . . . . . . . . . . . . . .. 261
Contents IX
Effects of Different Calcium Blockers and Implications Regarding Therapy
o£ Hypertrophic Cardiomyopathy
Synopsis. G. KOBER . . . . . . . . . . . . . . . . . . . . . .. 268
The Antianginal Efficacy of Seven Different Calcium Antagonists.
H.-J. BECKER, R. HOPF, G. KOBER, and M. KALTENBACH. With 2 Figures 269
Differentiation of Calcium-Antagonistic Drugs with Respect to Their
Myocardial Effects. R. KAUFMANN, R. BAYER, R. RODENKIRCHEN,
and R. MANNHOLD. With 4 Figures ............ 276
The Concept of Calcium Antagonist Therapy in Cardiac Hypertrophy.
Different Calcium Antagonists with Respect to Therapeutic Efficacy
in Hypertrophic Cardiomyopathy. Combined Therapy with
Calcium Antagonists and Other Drugs? M. KALTENBACH, G. KOBER,
and R. HOPF. With 1 Figure . . . . . . . . . . . . . . . . . 285
Clinical Pharmacology of Verapamil in Hypertrophic Cardiomyopathy
Synopsis. R. G. McALLISTER, Jf. ............... 290
Pharmacokinetics, Bioavailability, and ECG Response ofVerapamil in Man.
M. EICHELBAUM and A. SOMOGYI. With 3 Figures ...... 291
Verapamil Plasma Concentrations and Indices of Heart Size in Hyper
trophic Obstructive Cardiomyopathy - Evidence for the Existence
ofa Therapeutic Range. B. G. WOODCOCK, R. HOPF,
and R. KIRSTEN. With 8 Figures .............. 298
Plasma Verapamil Levels in Patients with Hypertrophic Cardiomyopathy:
Interpatient Variability and Clinical Usefulness. M. B. LEON,
D. R. ROSING, and S. E. EpSTEIN. With 6 Figures ....... 309
Correlation ofVerapamil Plasma Levels with Electrocardiographic and
Hemodynamic Effects. R. G. McALLISTER, Jf. With 3 Figures 322
Subject Index . . . . . . . . . . . . . . . . . . . . . . . . . .. 332
List of Contributors
BAYER, R., Physiologisches Institut der Universitat Dusseldorf, MoorenstraI3e 5,
D-4000 Dusseldorf
BECKER, H.-J., Medizinische Klinik I des Stadtkrankenhauses Hanau, LeimenstraI3e
20, D-6450 Hanau I
BIAMINO, G., Medizinische Klinik und Poliklinik, Klinikum Steglitz, Freie Univer
sitat Berlin, Hindenburgdamm 30, D-lOOO Berlin
BLEIFELD,W., II. Medizinische Klinik und Poliklinik, Kardiologische Abteilung,
Universitats-Krankenhaus Eppendorf, MartinistraI3e 52, D-2000 Hamburg 20
BLUSCHKE, V., Medizinische Klinik und Poliklinik, Klinik B (Schwerpunkt Kardio
logie), Universitat Dusseldorf, MoorenstraI3e 5, D-4000 Dusseldorf
BONOW, R. 0., Cardiology Branch, National Heart, Lung, and Blood Institute,
National Institutes of Health, Bethesda, MD 20205/USA
BUBENHEIMER, P., Benedikt-Kreutz-Rehabilitationszentrum flir Herz- und Kreis
laufkranke e.V., Sudring 15, D-7812 Bad Krozingen
BUSSMANN, W.-D., Zentrum der Inneren Medizin, Abteilung flir Kardiologie, Klini
kum der Johann-Wolfgang-Goethe-Universitat, Theodor-Stern-Kai 7, D-6000
Frankfurt/Main 70
CONDIT, J. R., Cardiology Branch, National Heart, Lung, and Blood Institute,
National Institutes of Health, Bethesda, MD 20205/USA
EICHELBAUM, M., Medizinische Klinik der Universitat Bonn, Siegmund-Freud
Str. 25, D-5300 Bonn
EpSTEIN, S. E., Cardiology Branch, National Heart, Lung, and Blood Institute,
National Institutes of Health, Bethesda, MD 20205/USA
FLECKENSTEIN, A., Physiologisches Institut der Universitat Freiburg, Hermann-Her
der-StraI3e 7, D-7800 Freiburg i. Br.
FREY, M., Physiologisches Institut der Universitat Freiburg, Hermann-Herder
Str. 7, D-7800 Freiburg i. Br.
FUSTER, V., Section of Cardiovascular Surgical Research, Mayo Clinic, 200 First
Street SW, MN 55901lUSA
GOODWIN, J. F., Royal Postgraduate Medical School, Hammersmith Hospital,
Ducane Road, GB-London W12 OHS
XII List of Contributors
GOTTDIENER, J. S., Cardiology Branch, National Heart, Lung, and Blood Institute,
National Institutes of Health, Bethesda, MD 20205/USA
HANRATH, P., II. Medizinische Klinik und Poliklinik, Kardiologische Abteilung,
Universitats-Krankenhaus Eppendorf, MartinistraBe 52, D-2000 Hamburg 20
HIRZEL, H. 0., Medizinische Poliklinik, Departement flir Innere Medizin, Universi
tat Zurich, RamistraBe 100, CH-S091 Zurich
HOPF, R., Zentrum der Inneren Medizin, Abteilung flir Kardiologie, Klinikum der
Johann-Wolfgang-Goethe-Universitat, Theodor-Stern-Kai 7, D-6000 Frankfurt!
Main 70
HUBNER, K., Zentrum der Pathologie, Klinikum der Iohann-Wolfgang-Goethe-Uni
versitat, Theodor-Stern-Kai 7, D-6000 Frankfurt/Main 70
JENNI, R., Medizinische Poliklinik, Departement flir Innere Medizin, Universitat
Zurich, RamistraBe 100, CH-S091 Zurich
KALTENBACH, M., Zentrum der Inneren Medizin, Abteilung flir Kardiologie, Klini
kum der Johann-Wolfgang-Goethe-Universitat, Theodor-Stern-Kai 7, D-6000
Frankfurt!Main 70
KAUFMANN, R., Physiologisches Institut der Universitat Dusseldorf, MoorenstraBe
5, D-4000 Dusseldorf
KAYE, M. P., Section of Cardiovascular Surgical Research, Mayo Clinic, 200 First
Street SW, Rochester, MS 55901lUSA
KEIDEL, I., Physiologisches Institut der Universitat Freiburg, Hermann-Herder
Str. 7, D-7S00 Freiburg i. Br.
KENT, K. M., Cardiology Branch, National Heart, Lung, and Blood Institute,
National Institutes of Health, Bethesda, MD 20205/USA
KIRSTEN, R., Abteilung flir Klinische Pharmakologie, Klinikum der Johann-Wolf
gang-von-Goethe-Universitat, SandhofstraBe 74, D-6000 Frankfurt!Main
KOBER, G., Zentrum der Inneren Medizin, Abteilung flir Kardiologie, Klinikum der
Johann-Wolfgang-Goethe-Universitat, Theodor-Stern-Kai 7, D-6000 Frankfurt!
Main 70
KOCH, I.-P., National Heart, Lung, and Blood Institute, National Institutes of
Health, Bethesda, MD 20205/USA
KOHLER, E., Medizinische Klinik und Poliklinik, Klinik B (Schwerpunkt Kardiolo
gie), Universitat Dusseldorf, MoorenstraBe 5, D-4000 Dusseldorf
KONRAD, A., Medizinische Klinik der Bundesknappschaft, Akademisches Lehr
krankenhaus der Universitat des Saarlandes, Lazarettstr. 4 D-6603 Sulzbach
KRAYENBUEHL, H. P., Medizinische Poliklinik, Departement flir Innere Medizin,
Universitat Zurich, RamistraBe 100, CH-S091 Zurich
KREMER, P., II. Medizinische Klinik und Poliklinik, Kardiologische Abteilung,
Universitats-Krankenhaus Eppendorf, MartinistraBe 52, D-2000 Hamburg 20
List of Contributors XIII
KUBLER, W., Abteilung Innere Medizin Ill, Medizinische Klinik der Universitat
Heidelberg, Bergheimer StraBe 58, D-6900 Heidelberg
KUHN, H., Medizinische Klinik und Poliklinik, Klinik B (Schwerpunkt Kardiolo
gie), Universitat Dusseldorf, MoorenstraBe 5, D-4000 Dusseldorf
KUNKEL, B., Zentrum der Inneren Medizin, Abteilung fUr Kardiologie, Klinikum
der Iohann-Wolfgang-Goethe-Universitat, Theodor-Stem-Kai 7, D-6000 Frank
furt! Main 70
LEON, M. B., Cardiology Branch, National Heart, Lung, and Blood Institute, Nation
al Institutes of Health, Bethesda, MD 20205/USA
LEUNER, c., Medizinische Klinik und Poliklinik, Klinik B (Schwerpunkt Kardiolo
gie), Universitat Dusseldorf, MoorenstraBe 5, D-4000 Dusseldorf
LIpSON, L. c., Cardiology Branch, National Heart, Lung, and Blood Institute,
National Institutes of Health, Bethesda, MD 20205/USA
LIU, S.-K., Departments of Pathology and Medicine, The Animal Medical Center,
New York, NY/USA
L6sSE, B., Medizinische Klinik und Poliklinik, Klinik B (Schwerpunkt Kardiologie),
Universitat Dusseldorf, MoorenstraBe 5, D-4000 Dusseldorf
LOOGEN, F., Medizinische Klinik und Poliklinik, Klinik B (Schwerpunkt Kardiolo
gie), Universitat Dusseldorf, MoorenstraBe 5, D-4000 Dusseldorf
LOSSNITZER, K., Medizinische Klinik der Bundesknappschaft Sulzbach/Saar, Aka
demisches Lehrkrankenhaus der Universitat des Saariandes, Lazarettstr. 4
D-6603 Sulzbach
MANNHOLD, R., Physiologisches Institut der Universitat Dusseldorf, MoorenstraBe
5, D-4000 Dusseldorf
MARON, B. 1., Cardiology Branch, National Heart, Lung, and Blood Institute,
National Institutes of Health, Bethesda, MD 20205/USA
MATHEY, D. G., II. Medizinische Klinik und Poliklinik, Kardiologische Abteilung,
Universitats-Krankenhaus Eppendorf, MartinistraBe 52, D-2000 Hamburg
McALLISTER, Ir., R. G., Veterans Administrations Medical Center, Lexington, Ken
tucky, KY 40507/USA
MOHR, W., Abteilung Pathologie der Universitat Ulm, Oberer Eselsberg, M 23,
D-7900 Ulm
MORROW, A. G., National Heart, Lung, and Blood Institute, National Institutes of
Health, Bethesda, MD 20205/USA
MULLER, A., Kerckhoff-Klinik der Max-Planck-Gesellschaft, BenekestraBe 6 - 8,
D-6350 Bad Nauheim
VON OLSHAUSEN, K.-E., Abteilung Innere Medizin III, Medizinische Klinik der
Universitat Heidelberg, Bergheimer StraBe 58, D-6900 Heidelberg
ROBERTS, W. c., Pathology Branch, National Heart, Lung, and Blood Institute,
National Institutes of Health, Bethesda, MD 20205/USA