Heart Failure : Pathophysiology, Molecular Biology, and Clinical Management

The treatment of heart failure has shifted over the years from the administration of diuretic agents to the provision of positive inotropic support to the inhibition of the neurohumoral axis. The changes in treatment reflect changes in concepts of the pathophysiology of heart failure. One attractive idea is the crucial role of cardiac hypertrophy as an adaptive and maladaptive process. This idea has recently been extended by delineating the opposing (yet related) pathways leading to cell death. Great efforts have been made to understand the processes leading to hypertrophy, such as the response of the myocardium to physical stress (i.e., pressure overload) at the cellular and molecular levels. Indeed, we may soon be at the stage where such insights can be tested as treatment strategies in animals and humans.

Basic scientists may view heart failure as a disorder caused by altered stress pathways or by mutations of one or more genes. But since heart failure is a clinical syndrome, basic scientists must understand its clinical aspects and clinicians must have the ability to talk to basic scientists about its molecular features. To do this, clinicians need to know about the potential, methods, and tools of molecular biology as they pertain to cardiac hypertrophy and failure. Several books on heart failure attempt to provide these links, ranging from small compendiums to large textbooks. Is another one necessary?

The particular strength of this book on heart failure is that it was written by one expert. Arnold Katz has been a witness to the evolution of concepts in heart failure for over 40 years and has maintained a deep understanding of the relevant basic science and its advances while treating numerous patients with heart failure. The result is a book that integrates recent insights into signal transduction, cell-cycle processes, apoptosis, oxidative stress, and the role of nitric oxide with organ physiology, hemodynamic defense mechanisms, clinical findings, and therapeutic approaches. This is an important feature of the book, since basic scientists and clinicians may underestimate the interactions of the numerous pathways and mechanisms involved in heart failure.

This well-written, concise book provides the link between seminal clinical observations and novel findings at the molecular level. It begins with the evolution of concepts of heart failure and classic organ physiology and continues with an up-to-date discussion of the biochemistry of myocytes. Readers will learn that heart failure is more than the sum of stress pathways. Katz has made an effort to put into perspective the roles of G protein-coupled receptors, downstream signaling events, the regulation of gene transcription and the involvement of transcription factors, the cytoskeleton, and ion channels.

Katz covers a wide array of basic and clinical observations, but there are some minor slips. One is the incomplete description of the interactions within stress pathways (i.e., gp130 is linked not only to STAT activation but also to ras and the MAP-kinase pathway, and the disruption of gp130 results in myocyte apoptosis despite the presence of hypertrophy). Also, the role of the fas ligand or fas in myocyte apoptosis and the role of nuclear factor-(kappa)B activation by JAK in cardiomyocytes may be less clear than the text and some of the figures suggest.

This book is a pleasure to read, and I strongly recommend it to all physicians and basic scientists dealing with heart failure. It provides the integrated insights required to elucidate new mechanisms and apply them clinically.

Helmut Drexler, M.D.
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