CRC HRT FAIL PDF

Preface

Heart failure is a growing world-wide epidemic with a prevalence of more than 5 million cases in the United States and 6.5 million cases in Europe. Epidemiologic data demonstrate a rapid increase in its incidence during the past two decades. This trend is likely to continue as the population ages. It is currently the most common hospital discharge diagnosis for patients over the age of 65 years and accounts for substantial morbidity and high mortality. Fortunately, major advances have occurred in our understanding of the cellular mechanisms, pathophysiological abnormalities, nonpharmacologic therapy and surgical therapeutic options for this syndrome during the past decade. This textbook focuses the most recent developments in the pathogenesis, etiologic considerations, diagnosis, and treatment of heart failure and has been written by internationally recognized physicians and scientists involved on a daily basis in heart failure research and clinical care.

The authors' aim is to provide an up-to-date and comprehensive review of the diagnosis and treatment of heart failure. The text is divided into five sections that concisely summarize fundamental cellular and molecular bases for heart failure, its pathophysiology, current invasive and noninvasive diagnostic techniques, pharmacologic advances and device- based therapy, surgical options, and evolving molecular therapies. The first section focuses on the tremendous advances that have occurred over the last decade in our understanding of the basic mechanisms of heart failure. These discoveries have reshaped our understanding of the basic causes of "the heart failure phenotype" and will allow us to redesign therapeutic strategies for the treatment of this disease. These chapters specifically focus on the genetics of dilated and hypertrophic cardiomyopathy, the role of hypertrophy and apoptosis, beta-adrenergic receptor signaling, and excitation-contraction coupling abnormalities that contribute to ventricular dysfunction. In each of these chapters, the role of new tools, such as microarray analysis, proteomics, and molecular imaging are detailed.

The second section summarizes recent insights into the activation of vasoconstrictor and vasodilator pathways, including a host of crucial neurohormones and cytokines. Ischemic left ventricular remodeling, cardiomyopathies of the adult, and diagnostic and etiologic considerations in diastolic heart failure complete this section.

The third section summarizes current diagnostic methodologies and nonsurgical treatment options. Prognostic markers including brain natriuretic peptides (BNP) are highlighted. Recent pivotal multicenter clinical trials that have evaluated the therapeutic efficacy of beta-adrenergic blockers, angiotensin-receptor antagonists, aldosterone antagonists, and endothelin antagonists are included. Indications and intermediate-term outcomes for cardiac resynchronization therapy are highlighted. National practice guidelines for heart failure management from the American Heart Association, American College of Cardiology and the Heart Failure Society of America are also critically reviewed.

Despite the tremendous success of contemporary pharmacologic treatment, heart failure remains a progressive disease and the fourth section of the book focuses on the growing variety of surgical options that are now being adopted for its treatment. The expanding indications for coronary revascularization and mitral valve repair are summarized. Newer ventricular remodeling procedures, such as the Dor procedure and external cardiac restraint devices, are reviewed. The contemporary role of cardiac transplantation, outcome of outpatient left ventricular circulatory support, and the current status of total artificial heart devices are included.

The next generation of therapies will unquestionably be directed at molecular targets in the failing myocardium. The last section includes viral-based gene therapies to restore depressed myocardial contractility, and both stem cell and nonstem cell cellular transplantation techniques designed to repopulate the failing left ventricle. Ongoing advances in vector and stem cell technology, cardiac cell and gene delivery, and, most importantly, our understanding of heart failure pathogenesis, encourage consideration of molecular therapies for heart failure. At the present time, strategies that enhance sarcoplasmic calcium transport, are supported by substantial evidence in both cardiomyocytes derived from heart failure patients and animal models. Initial studies evaluating other novel targets appear promising but have not been as fully evaluated. In ongoing efforts to target cardiac dysfunction, gene and cell transfer provide an important tool to improve our understanding of the relative contribution of specific pathways. Through such experiments, molecular targets can be validated for therapeutic intervention whether pharmacologic or genetic. However, translating these basic investigations into clinical gene therapy for heart failure remains a formidable challenge. The last section of this book will closely examine the problems and hope for these novel strategies. Nevertheless, practical advances and our growing understanding of the molecular pathogenesis of heart failure provide reason for cautious optimism.

This book will be of particular interest to clinical cardiologists and primary care specialists involved in the daily care of patients with ventricular dysfunction and symptomatic heart failure. Physician-scientists will also find it useful for integrating mechanistic laboratory observations with recent clinical advances. Finally, it should appeal to cardiovascular surgeons whose clinical or research interests involve nonpharmacologic treatment of the failing ventricle. Despite the marked increase in heart failure prevalence, there are many reasons for optimism that more accurate diagnosis and more individualized, diseasefocused treatment strategies will soon be available. The scientific and clinical approaches to heart failure management are undergoing dramatic evolution; physicians and surgeons who care for such patients will benefit from the insights provided into current and future therapies available in this text.