Heart Failure: Pathogenesis and Treatment
Authors: Andrew J S Coats
Journal: Journal of the Royal Society of Medicine (2002)

Chronic heart failure is increasing in prevalence and putting a growing burden on health services. One reason for this is our success in salvaging lives from large myocardial infarction and in improving the outlook for patients with moderate and severe heart failure; another is the ageing of the population. Despite improvements in the prevention of heart failure by new antihypertensive and hypolipidaemic therapies this trend seems set to continue; indeed, a worldwide epidemic of heart failure is beginning as African, Asian and East European countries adopt western habits of diet and lack of physical exercise. Against this background, heart failure care and research are advancing apace; most of the now standard treatments were introduced in the past two decades. At basic level much has been learned from the functioning of isolated myocytes—their interaction with the myocardial cytoskeleton and interstitial tissue—and clinical research has begun to elucidate the complex neurohormonal, immunological and endocrine maladaptations that occur in chronic heart failure. In addition, our knowledge of clinical physiology and pathophysiology at the cellular, organ and whole body level is increasing fast. Lastly, but most importantly, the evidence base in terms of large-scale randomized clinical trials is growing very quickly and has established unequivocal benefit from treatments such as angiotensin converting enzyme inhibitors, beta-blockers and spironolactone. Other treatments that looked promising have been found ineffective. Non-pharmaceutical approaches under development include ventricular assist devices and electrical resynchronization. The years to come will be an era of molecular gene therapy, stem cell therapy and novel small molecules fashioned from knowledge of molecular biology of the failing heart.

The weighty tome by Narula and colleagues is thus well timed. Comprehensive but approachable, it is amply illustrated by figures, explanatory tables and cartoons. The format is conventional, moving from basic scientific principles to pathogenic mechanisms, then management. The account of the surgical management of end-stage heart failure is unusually detailed, whereas the overview of medical treatment of heart failure is too brief at 11 pages to do justice to the wealth of data from clinical trials. The main strength of the book is the material on mechanisms. Many of the real experts are here, including Arnold Katz on the cellular and molecular basis of myocardial contraction. The explanation of the current carrying channels of the myocyte is very elegantly presented. The level of detail is sufficient to allow a clinician to grasp basic processes and to envisage where we can next look for progress in our understanding of cardiomyopathy. Conventional ventricular mechanics and haemodynamics are well covered and there is an authoritative chapter by J S Ingwall on the evolving field of myocardial energetics. Insights are presented on the increasingly complex gene pathways for the expression of hypertrophy and the transition from hypertrophy to failure. This leads in well to a more conventional histological classification and description of the cardiomyopathic disorders. Indeed, myopathies dominate, and clinical management of secondary ischaemic cardiac failure is dealt with in less depth. The neurohormonal, immune and endocrine adaptations are well covered but there is little on cytokine activation, so important in the progression of heart failure. Apoptosis gets its own chapter and there are separate chapters on inflammation, matrix remodelling and altered iron channel expression. More clinically oriented chapters cover hypertensive heart disease, the myocardium in diabetes mellitus and infective diseases (including HIV-related cardiomyopathy). Ischaemic heart disease is accorded just one chapter.

I recommend this text to those working in heart failure research and to cardiologists who wish to keep abreast of developments in this expanding area. The emphasis is on cardiomyopathic processes at cellular and organic level; in other words, this is not a clinical ‘how-to’ text.