Bücher der Reihe Developments in Cardiovascular Medicine

Cardiovascular drug therapy has markedly progressed in the recent decades. Not only have new drugs been introduced to clinical practice, but new classes of drugs have been developed. While in 1960 the practicing cardiolo­ gist had a selection of about only ten drugs, in 1987 about 150 drugs are routinely used in cardiovascular diseases. Elderly patients, however, usually do not enjoy the full benefit of this progress. This might be due to lack of knowledge, a conservative approach, or the worldwide tendency not to try new drugs in the elderly. It is now clear that the majority of patients that will be treated in car­ diovascular clinics will be, in the near future, elderly patients. Even now, elderly patients form about one-third of the patients with cardiovascular diseases. These patients are approached, however, according to criteria devel­ oped for younger populations. This is despite the fact that elderly patients differ from younger ones in most aspects, including pathology, epidemiol­ ogy, pathophysiology, diagnostic approach, management, pharmacology, pharmacokinetics, rehabilitation, and supportive treatment. It is the purpose of this book to present to the clinician all drugs with which there is clinical experience in the elderly or which might be potentially useful for the elderly with cardiovascular diseases. The data are presented without the authors taking a position. This should allow the clinicians to make their own selection and individualize treatment, vii viii Preface based on a wide data base. Comparative data are presented only when specific comparative studies were performed.

Knowledge of cardiac ion channels and transporters has advanced remarkably in the last two decades with the development of patch-clamp and molecular biological techniques. This textbook offers a comprehensive overview of structures and functions of ion channels and transporters in the heart. Readers are first introduced to the molecular biology and electrophysiology of all the important ion channels. After discussing their developmental changes, the pharmacology and pathophysiology of clinically-relevant ion channels are reviewed. Molecular aspects of the cardiac excitation-contraction coupling and intracellular Ca2+ regulation by ion transporters are also described. The book will be useful to electrophysiologists, cardiac physiologists and pharmacologists, and molecular biologists interested in ion channels at all levels. For research specialists, the book will provide a perspective of the field. The book can be used as a reference source for working scientists in the fields of ion channels, biophysics, cardiac electrophysiology, and pharmacology. It is aimed at graduate and medical students, designed for use as a textbook for graduate and medical courses.

Pediatric cardiology is celebrating in the 1990s the 50th anniversary of the beginnings of the age of therapy. This informal `history' describes how the discipline grew from the era of pathologic anatomy to the dawn of therapy, the beginnings of closed heart surgery between 1939 and 1945. That dawn ushered in a remarkable half century of change and growth, leading from clinicophysiologic correlations through the start of open heart surgery in the 1950s. The text celebrates some of the achievements of this vivid and heroic age, and describes how, in the mid 1970s, new surgical and medical approaches, including prostaglandins and Doppler echocardiography, led to successful cardiac treatment in infancy, the `infant era'. Interventional cardiology and the study of childhood arrhythmias began. Now, in the 1990s, a new era emphasising molecular biology and cardiac development is growing from the tools and concepts of the past. The four eras have focused on pathologic anatomy, clinicophysiologic correlations and surgery, heart problems in infancy, and now the developing heart. In each era there have been advances in the four domains of pediatric cardiology, the heart before birth, the normal heart, heart disease and defects, and preventive cardiology. Growth in knowledge has been both episodic and dramatic, yet not a picture of unalloyed achievement. The later chapters discuss some of the problems beginning to be recognised in the new and current `developmental era'. The pioneers of pediatric cardiology, both men and women, are more than eponyms, for each used in new and original ways the tools and concepts available in their era. The interaction of tools and concepts is a theme in this book. Just as the tool of the stethoscope was vital in delineating the clinical profile of ventricular septal defect and patent ductus, the fluoroscope played a role in developing the concept of the Blalock Taussig shunt. Pioneers also includepatients and their families, and the book includes some discussion of what little is known of childhood and of the child with heart disease in the four different eras. This is a brief overview of the growth of knowledge of children's hearts from before William Harvey until our own time, and includes references to histories of cardiac surgery and to collections of classic cardiac papers. By its emphasis on the child as the central historic figure, and on the interaction of tools and concepts in the growth of knowledge, the text provides a celebratory approach to the 50th anniversary of modern pediatric cardiology.

Catheter-delivered therapeutic ultrasound angioplasty is a new technique for use in the treatment of obstructive vascular disease. The treatment differs from balloon angioplasty in that it has been shown experimentally to cause disintegration of calcific and fibrotic atherosclerotic plaques, thrombus dissolution and arterial vasodilation. In contrast to laser technology, ultrasound systems are relatively inexpensive and simple to use and maintain. In the clinical trials detailed in this text, ultrasound angioplasty has been shown to be feasible and safe. Ultrasound Angioplasty is a comprehensive text, addressing the theoretical, experimental and clinical issues. The international contributions reflect the excitement, interest, spirit and cooperation in the research and development of therapeutic ultrasound.

Angioplasty has completely transformed the treatment of coronary artery disease and is widely used, with more than 800,000 procedures performed worldwide per year. However, the enthusiasm for angioplasty is shadowed by restenosis, which remains a critical problem after the procedure, resulting in clinical recurrence in over a third of patients. Recently, the mechanisms of restenosis have been completely reappraised with an enriched understanding that the original concept of neointimal hyperplasia may not be accounting for the bulk of the problem. There is a desperate need to heighten understanding of the remodeling process at the molecular, cellular, and arterial level. Vascular remodeling is a well established concept in the field of atherosclerosis and hypertension, but only in recent years has its applicability to the field of restenosis become pivotal. Accordingly, the editors perceived the need to assemble the first book dedicated to the concept of coronary artery remodeling in restenosis, in order to clearly review the experiments leading to the remodeling hypothesis and integrate this with the neointimal hyperplasia (tumor) model for the development of the restenotic lesion. The authors of this book present their experience to facilitate the understanding of the mechanisms for coronary restenosis and remodeling. The various experimental models, clinical issues, and basic mechanisms are reviewed in detail, resulting in a fresh approach to a vexing clinical problem. Arterial Remodeling: A Critical Factor in Restenosis will be useful to the physician and trainee who have an interest in restenosis, and specifically in the major pathophysiologic process which determines the fate of arterial healing in patients following percutaneous coronary revascularization. It is hoped that this book will lay the foundation for more effective therapies that will reduce the chance of constrictive remodeling and improve the long-term efficacy of non-surgical coronary revascularization in the future.

This book is timely and challenging. Within its pages are commentaries and opinions on the scientific background and explanatory ideas for a complex of symptoms and investigations known as syndrome X. The commonest cause by far of angina pectoris is coronary artery obstruction due to atheromatous lesions both within the wall of the artery and intruding into the lumen; in such patients it is expected that there maybe ST segment depression on atrial pacing or on an exercise test indicating myocardial ischemia. Syndrome X was a term first used in an editorial written by Kemp in 1973. He was referring to patients in group X in a paper from Arbogast and Bourassa. Patients in group X had three features, namely angina as judged on a clinical history, alterations of the ST segment on the electrocardiogram during atrial pacing and smooth unobstructed coronary arteries (presumed normal) as assessed by the technique of coronary angiography. The changes on the electrocardiogram, conventionally indicative of myocardial ischemia, could not be explained on the basis of any abnormality of the coronary arteries and Kemp named the complex of fmdings syndrome X because of this seeming paradox and the lack of a single explanation. In the last thirty-one years there has been substantial scientific interest in this syndrome giving rise to a large number of publications. The name syndrome X has led to considerable confusion. Physicians are familiar with the X chromosome and with X linked congenital disorders.

The cardiac system represents one of the most exciting challenges to human ingenuity. Critical to our survival, it consists of a tantalizing array of interacting phenomena, from ionic microscopic transport, membrane channels and receptors through cellular metabolism, energy production to fiber mechanics, microcirculation, electrical activation to the global, clinically observed, function, which is measured by pressure, volume, coronary flow, heart rate, shape changes and responds to imposed loads and pharmaceutical challenges. It is a complex interdisciplinary system requiring the joint efforts of the life sciences, the exact sciences, engineering and technology to understand and control the pathologies involved. The Henry Goldberg Workshops were set up to address these challenges. Briefly, our goals are: 1. To foster interdisciplinary interaction between scientists from different areas of cardiology, identify missing links, and catalyze new questions. 2. To relate micro scale cellular phenomena to the global, clinically manifested cardiac function. 3. To relate conceptual modeling and quantitative analysis to experimental and clinical data. 4. To encourage international cooperation so as to disperse medical and technological know how and lead to better understanding of the cardiac system. Today we celebrate the 7th birthday of a dream come true; a dream to bring together the diversified expertise in the various fields of science, engineering and medicine, to relate to the numerous interactive parameters and disciplines involved in the performance of the heart.

As the majority of cardiovascular deaths are related to myocardial ischemia, it is necessary to understand the various aspects of ischemic heart disease. In this regard, it is noteworthy that ischemic heart disease is commonly associated with atherosclerosis, coronary spasm, as well as thrombosis leading to the development of arrhythmias, cardiovascular cell damage, myocardial infarction, cardiac hypertrophy and congestive heart failure. Furthermore, it is also important to appreciate various physiological, electrophysiological and biochemical processes in the normal heart if we are to understand their significance under pathological situations. Heart Function in Health and Disease has been organized in five sections to provide an outline of a complex problem in a convenient manner. One section of this book is devoted to shedding light on the restructuring and ontogenic changes in the developing heart whereas in the next section some hypertrophic alterations due to chronic hypoxia are described. The third and fourth sections of this book are concerned with the regulation of cardiac channels as well as signal transduction mechanisms and cardiac electric field. The fifth section contains some pathophysiological events during the development of cardiac hypertrophy and heart failure. All of these areas encompass a significant body of new information that will be invaluable to those who work in the field of cardiovascular sciences, as well as those who treat people with heart disease.

This book is based on papers presented at a Symposium held in Seoul, Korea in 1992. The idea for the symposium developed naturally from work in which Professor Yung E Earm, at Seoul National University, had been involved both in my laboratory in Oxford and in his own laboratory in Seoul concerning the possible role of certain amino acids, like taurine that are strongly concentrated by the cells of the heart, and the relationship between such acids and membrane ionic currents. The first obvious question was whether it is possible to identify the transport mechanisms involved for taurine and whether they are electrogenic. The second question is what function could be served by such processes: does taurine play an essential role in cardiac tissue and is this important in protecting the heart from disease? With his colleagues in the Korean Physiological Society, Professor Earm set about the task of fmancing and organizing a meeting at which some of the world's leading cardiac electrophysiologists and taurine specialists could discuss these questions. The fmance was generously provided by the Dong-A Pharmaceutical Company, one of the leading scientific companies in Korea.

Although there are many books on angina, few are devoted to the important problem of how to evaluate drug efficacy in angina pectoris. Drug Evaluation in Angina Pectoris has two fundamental aims: the first is to review the methodological aspects of drug evaluation in stable and unstable angina pectoris; the second is to provide a logical and methodological background for future studies aimed at assessing the ability of medical treatment to improve prognosis. Part I updates the pathophysiology, clinical presentation and prognosis of angina pectoris. Part II aims to `put in numbers' the symptoms and signs of myocardial ischemia, starting from a revision of the currently used parameters. It is extremely important to quantify the variability of the disease for the correct design of clinical trial, a subject dealt with in Part III, which also discusses some clinico-pharmacological aspects of therapy. Part IV is a critical review of the drugs currently used for the treatment of stable and unstable angina, and particularly considers some important unresolved issues concerning their use. The current FDA and EC guidelines for the evaluation of antianginal drugs are briefly discussed in Part V, giving clinical investigators insight into how antianginal drugs are evaluated by regulatory agencies and what is considered as proof of a valid efficacy/tolerability ratio. Drug Evaluation in Angina Pectoris will assist discerning cardiologists, pharmacologists, and advanced students of cardiology as well as innovative pharmaceutical companies, all of whom need to understand what angina is, how to evaluate treatment, and how to judge the agents used in its treatment.

Since it was introduced less than 100 years ago, analysis of the circulatory response to exercise as a measure of cardiac function has undergone remarkable development. Most recently this approach has incorporated the burgeoning technology of the last half of the 20th century to meet the physiological and diagnostic needs of scientist and clinicians. The ease of administration, economy and abundant data that characterize exercise testing for its relative staying power as the most frequently utilized noninvasive method of cardiovascular evaluation. The basic modalities of exercise electrocardiography of treadmill and bicycle have been extended by noninvasive cardiac imaging techniques, including scintigraphy and echocardiography, that have provided new insights in myocardial function during exertion and pharmacologic stress. At the same time, traditional exercise electrocardiography has also been refined by innovations that have broadened its applications. Exercise Testing: Current Concepts and Recent Advances affords the reader a state-of-the-art presentation of the diverse and expanding methods of exercise testing and their roles in patient management. The contributors to this volume include individuals who have made seminal contributions to the field during the last several decades. Indeed, it is legitimate to designate this group as a `Who's Who of Exercise Testing'. It is our hope that this book will enhance the reader's understanding of contemporary methods of exercise testing, as well as provide a glimpse into future directions of this science, that this knowledge is applied to optimal diagnosis and management of our patients.

From the Proceedings of the Meeting of the American Section of the International Society for Heart Research (ISHR) at Hilton Head, South Carolina, September 21-24, 1983

Non-Invasive Imaging of Atherosclerosis is a primer, reference and review of some of the key features of current activities in the field of atherosclerosis. The Editors' goal is to provide material and stimulating ideas to basic scientists and clinical researchers in order to extend the application of vascular imaging and to further develop methods suitable for investigation of the arterial wall. The first section presents current knowledge about pathology, vascular mechanics and compensatory mechanisms active during atherogenesis. It explores the early lesion, complications of plaques and early detection of plaques. Section II reviews several key methodological issues of B-mode ultrasound imaging and some of the most current data. Quantitative B-mode ultrasound is an established non-invasive tool widely used in large epidemiologic studies and interventional clinical trials of atherosclerosis. The last section addresses the most promising areas of development in vascular imaging. This involves new techniques to evaluate the atherosclerotic bed, to follow atheroma progression/regression and to evaluate vascular mechanics in atherosclerotic arteries. The last chapter places the application of non-invasive imaging in perspective.

Cardiac output has always been a subject of interest to both clinicians and researchers in different branches of medicine and surgery. In the last decade more attention has also been paid to its application in pediatrics, neonatology, fetal medicine and pregnancy. Better understanding of the peripheral circulation has provided more insight into the patholophysiology of different diseases. Many cardiac and non-cardiac disorders affect cardiac outputs. Monitoring of the changes in cardiac output is also important in the acutely ill patient. There are several methods to measure cardiac output, each with advantages and pitfalls. This book deals with all relevant aspects of cardiac output in eight parts: part one describes the methods of measuring cardiac output and a comparison between the catheterisation based and the noninvasive techniques, while part two describes the changes in cardiac output due to physiological causes. Part three describes cardiac output in cardiac diseases and systemic hypertension. Cardiac output in acutely ill patients is discussed in part four. Effect of cardiac medications, temporary atrial pacing, permanent pacing, pharmacologic stress testing and anesthesia are covered in detail in part six, while changes in cardiac output in noncardiac diseases are described in part seven. Finally great attention has been paid in part eight to the regional circulation including cerebral, coronary, skeletal and splanchnic circulations. A separate chapter discusses in detail the dynamics of blood flow. This book will be useful both to the cardiologists as well as to physicians in other fields of surgery and medicine and to their trainees. Readers will find this book an interesting and a useful reference on the topic of cardiac output.

This volume constitutes the proceedings of a satellite symposium of the XXXth congress of the International Union of Physiological Sciences. The symposium has been held In Banff, Alberta Canada July 9-11 1986. The program was organized to provide a selective overview of current developments in cardiac biophysics, biochemistry, and physiology. In order to highlight areas of develop- ing ideas and to stimulate the participants' inquisitiveness into the nature and complexity of the integrated cardiovascular system, lectures and discussions were presented that emphasized evolving and sometimes provocative concepts in the field. With the same goal in mind we have, for the readers of this volume, briefly summarized the general discussions. We would like to thank several individuals whose dedication made this sym- posium and publication of the proceedings possible. Mrs. Lois Kokoski and Mrs. Madeleine Aldridge of the Conference Office of the University of Calgary seemingly effortlessly handled the details of the symposium. Peter de Tombe, Dr. Peter Backx and Dr. Jeroen Bucx transcribed the general discussions. Finally, we appreciate the extra effort of our secretaries, Lenore Doell and Gregory Douglas, and the work of Anna Tyberg who prepared the final manuscripts for publication. Henk E.D.J. ter Keurs, M.D. Ph.D. John V. Tyberg, M.D. Ph.D.

To our knowledge, this is the first book dealing exclusively with myocardial contrast two-dimensional echocardiography (MC-2DE), a new and exciting diagnostic methodology for assessment of myocardial perfusion, which has seen rapid development and has now entered the clinical stage. The experi- mental research and human applications have been described in technical papers published in a variety of journals, but our objective is to provide the reader with a comprehensive and concentrated overview of the field and of the current state of the art. To facilitate appreciation of the significant ad- vances made and issues yet to be resolved, we are pleased to have several well known specialists contribute their own assessment of specific aspects of MC- 20E and illustrate the method's principles as well as applications. We were faced with inevitable overlaps and some repetitions in the discussion of quan- titative potentials or limilations of the methodology. Rather than strictly 'streamlining' the text, we decided to accept some redundancy in the interest of presenting a diversity of points of views, reflecting the current evolutionary state of MC-20E. Following a brief reference to the established clinical contrast echocardiog- raphy, recent developments and validations of the specialized MC-2DE tech- nique are reviewed, bearing in mind that the field is in a flux and some of the ongoing activities have not as yet been formally reported. Mechanisms of the echo contrast and several new agents are decribed next, and an additional chapter illustrates current thoughts-on optimizing the echo contrast medium.