P.A.F.M. Doevendans – författare

The development of the heart and vessels during embryogenesis depends on the complex interplay of various cell types and growth factors. The implementation of molecular tools has enabled us to analyse early steps in cardiogenesis and vasculogenesis. Furthermore the introduction of transgenic and knock-out techniques in mice, and the miniaturization of physiologic measurements to the mouse level has fundamentally changed our knowledge. Pathophysiology can be unravelled at the molecular level. The implications of various stimuli on specific membrane receptors can be analyzed. In response to receptor activation, interacting intracellular signalling pathways can activate or block transcription factors. The changes in gene expression lead to functional changes observed in the cardiovascular systems of animal models and humans. Changes in the level of gene expression and protein function in cardiovascular disease are discussed for the sarcomeric, calcium handling and ion channel genes. Furthermore, different approaches to the design of cell-type-specific gene therapy approaches for the heart and vessels are outlined.

The first invasive evaluation of cardiac arrhythmias in humans was performed in 1967 in Paris (Prof. P. Coumel) and Amsterdam (Prof. D. Durrer). This was the start of a rapid increase in knowledge of the diagnosis, mechanism and treatment of cardiac arrhythmias. In that same year Prof. Hein J.J. Wellens became cardiologist in the Wilhelmina Gasthuis in Amsterdam. Initially in Amsterdam (1967-1977) and later on in Maastricht (from 1977), he was the driving force for many breakthroughs in clinical cardiac electrophysiology. With an active interplay between the knowledge derived from the 12-lead electrocardiogram and the recordings made with invasive electrophysiology, he composed new ideas leading to major contributions in clinical cardiac electrophysiology and, more generally, in arrhythmology. He published over 650 scientific papers and 142 books, and had numerous functions within scientific boards of prestigious journals. In addition he trained more than 120 cardiologists in clinical cardiac electrophysiology. On the occasion of the congress "2000, Future of Arrhythmology; Lessons From the Past, Promises For Tomorrow", the scientific work of Prof. Hein J.J. Wellens is highlighted.More than 60 articles over the whole time span have been selected. These articles are accompanied by comments from an expert, co-worker and/or former fellow in order to place the paper in a scientific time frame, including the relationship of the author with Prof. Hein J.J. Wellens.

This accessible handbook aims to help decision-making in cardiovascular patients with a potentially inherited disease. First of all, the basics of molecular cardiology are introduced, followed by contributions of molecular geneticists and clinical geneticists, to show the disciplines involved in DNA diagnostics. Clinicians from around the globe discuss the relevance of genetics for their field of interest covering atherosclerosis, cardiomyopathy and arrhythmias. In addition, some rare but relevant connective tissue diseases are covered. In all the chapters the importance of DNA dianostics are categorized. This varies from the notion that a disease is inherited without information on genetics (Category F), to diseases where the exact location of the molecular defect determines the therapy (Category A). This simple classification is provided for the known inherited diseases to help the physician on how to advise and direct the patients. This is not a textbook for geneticists, but a practical guide for clinicians. In addition, the chapters give insight in etiology, pathophysiology and treatment of inherited cardiovascular diseases.

This volume combines state-of-the-art chapters on technical advances in combination with applications in the different fields of cardiovascular medicine, including atherosclerosis, hypertension, cardiac hypertrophy and failure and arrhythmias. In addition, developments with respect to stem cell applications in cardiology are addressed, including cell source selection, manipulation and applications.

This volume, written by the leaders in the field, will provide a practical and comprehensive overview of the electrocardiogram (ECG). The ECG remains the most accessible and inexpensive diagnostic tool to evaluate the patient presenting with symptoms suggestive of acute myocardial ischemia. The ECG in Acute Myocardial Infarction and Unstable Angina, written by Drs. Hein Wellens, Anton Gorgels and Pieter Doevendans, is an excellent reference for any cardiac electrophysiologist, cardiologist, internist or emergency room physician.

Clinical management and signs are the focus of this practical cardiogenetic reference for those who are involved in the care for cardiac patients with a genetic disease. With detailed discussion of the basic science of cardiogenetics in order to assist in the clinical understanding of the topic.The genetic causes of various cardiovascular diseases are explained in a concise clinical way that reinforces the current management doctrine in a practical manner. The authors will cover the principles of molecular genetics in general but also specific to cardiac diseases. They will discuss the etiology, pathogenesis, pathophysiology, clinical presentation, clinical diagnosis, molecular diagnosis and treatment of each cardiogenetic disease separately. Therapy advice, ICD indications, indications for and manner of further family investigation will all be covered, while each chapter will also contain take-home messages to reinforce the key points. The chapters reviewing the different diseases will each contain a table describing the genes involved in each. Each chapter will also contain specific illustrations, cumulatively giving a complete, practical review of each cardiogenetic disease separately. Special emphasis will be given to advice on how to diagnose and manage cardiogenetic diseases in clinical practice, which genes should be investigated and why, and the pros and cons of genetic testing. Guidelines for investigation in families with sudden cardiac death at young age will also be included. This book will be written for the general cardiologist and the clinical geneticist who is involved in cardiac patients and will provide answers to question such as:Which genes are involved and which mutations? What is the effect of the mutation at cellular level? Which genes should be tested and why? What is the value of a molecular diagnosis? Does it influence therapy? When should the first degree relatives be tested and in which way?

Four years ago-in December 1997-the first European Science Foundation Workshop on Cardiovascular Specific Gene Expression was held in Maastricht. It was hardly possible to imagine the progress in the field in those four years. In 1997, gene expression was still an art focused on individual genes; in 200 I, many labs have access to micro-array facilities to determine the expression of thousands of genes simultaneously. In 1997, gene expression was an area of fundamental research in basis molecular biology laboratories; in 200 I, clinical cardiovascular research has incorporated gene expression approaches. In 1997, the interpretation of a gene expression experiment was usually straightforward; in 200 I, advanced bioinformatics tools are needed to approach the extreme complexities of genetic control of cell and tissue function. The second symposium in this series is focused on Cardiovascular Genomics. New Pathophysiological Concepts. The organizing committee chose to invite a group of renown scientists and young investigators around four topics of eminent importance in cardiovascular research. These topics reflect the major present-day clinical cardiovascular problems: atherosclerosis, hypertension, arrhythmias and heart failure. In addition to these four disease-driven topics, the workshop has sessions on gene expression methodologies and cellular transplant approaches to cardiovascular disease.

The electrocardiogram (ECG) remains the most accessible and inexpensive diagnostic tool to evaluate the patient presenting with symptoms suggestive of acute myocardial ischemia. It plays a crucial role in decision making about the aggressiveness of therapy especially in relation to reperfusion therapy, because such therapy has resulted in a considerable reduction in mortality from acute myocardial infarction. Several factors play a role in the amount of myocardial tissue that can be salvaged by reperfusion therapy, such as the time interval between onset of coronary occlusion and reperfusion, site and size of the jeopardized area, type of reperfusion attempt (thrombolytic agent or an intracoronary catheter intervention), presence or absence of risk factors for thrombolytic agents, etc. Most important in decision making on reperfusion therapy and the type of intervention is to look for markers indicating a higher mortality rate from myocardial infarction. The ECG is a reliable, inexpensive, non-invasive instrument to obtain that information. Recently it has become clear that both in anterior and inferior myocardial infarction, the ECG frequently allows not only to identify the infarct related coronary artery, but also the site of occlusion in that artery and therefore the size of the jeopardized area. Obviously, the more proximal the occlusion, the larger the area at risk and the more aggressive the reperfusion attempt.

The development of the heart and vessels during embryogenesis depends on the complex interplay of various cell types and growth factors. The implementation of molecular tools has enabled us to analyze early steps in cardiogenesis and vasculogenesis. Furthermore the introduction of transgenic and knock-out techniques in mice, and the miniaturization of physiologic measurements to the mouse level has fundamentally changed our knowledge. Pathophysiology can be unraveled at the molecular level. The implications of various stimuli on specific membrane receptors can be analyzed. In response to receptor activation, interacting intracellular signaling pathways can activate or block transcription factors. The changes in gene expression lead to functional changes observed in the cardiovascular systems of animal models and humans. Changes in the level of gene expression and protein function in cardiovascular disease are discussed for the sarcomeric, calcium handling and ion channel genes. Furthermore, different approaches to the design of cell-type-specific gene therapy approaches for the heart and vessels are outlined.

All physicians practicing medicine encounter patients suffering from cardiovascular disease. This book has been outlined in such a way that vascular surgeons, general internists, neurologists and cardiologists should be able to use it. The book covers the complete scope of cardiac diseases in addition to chapters on hypertension and atherosclerosis. In many patients there is a family history of cerebrovascular accidents, myocardial infarction or peripheral arterial disease. Also in patients reporting collaps, palpitations and arrhythmias the family is crucial and can provide clues to a genetic cause of the disease. This book is published to guide physicians in the process of determining whether a genetic component is likely to be present. Furthermore, information is provided what the possibilities and limitations of DNA diagnostic techniques are. Finally, the importance of newly identified categories of potential patients, i. e. gene carriers without symptoms or any inducible sign of disease, is highlighted. For some patients a genetic diagnosis is essential to determine appropriate therapy and for counseling? In some other diseases DNA diagnostic tools are available but the relevant for the patients may be less clear. In other families the search for a disease causing gene is ongoing and the possibilities to find genes and to unravel the pathophysiology of the disease is limited by the lack of patients. To give insight into the current state of genetic diagnostics, the authors have classified the cardiovascular diseases.