Pathophysiology of Heart Failure

Abstract

Heart failure (HF) has become a public health issue that is so important that it has been named a “new epidemic of cardiovascular disease,” and its prognosis is poor. The 5-yr mortality rate in patients with mild HF is approx 50%; the annual mortalities depend on disease severity and range from <5% in asymptomatic patients to 30–80% in endstage disease, with 10% in mild HF and 20–30% in moderate HF (1). Today, HF is the single most frequent cause of hospitalization in persons 65 yr of age or older (1). HF becomes more common with increasing age. The increase in the aging of the population and the growing number of people surviving myocardial infarctions are important reasons why the prevalence of HF has been rising steadily. Fortunately, during the last three decades substantial improvements in the diagnosis, management, and treatment of patients with HF have been achieved. Drugs have become available that have been demonstrated unequivocally to delay death, enable patients to avoid hospitalization, and improve the quality of life assessed by exercise capacity and symptoms questionnaires. In the 1970s HF was perceived as a disease with symptoms that were closely allied to hemodynamic disequilibrium. This hemodynamic model suggested that increased ventricular wall stress is the principal cause of HF. It was thought that these abnormalities can be rectified by the use of vasodilating drugs that lead to afterload reduction. These drugs in fact lowered left atrial pressure and increased cardiac output, and acute HF symptoms are rapidly improved by the use of drugs such as diuretics, vasodilators, and morphine. This response relates largely to changes in central hemodynamics. However, it was soon realized that the administration of some of these afterload-reducing drugs was not associated with any clinical benefit on patients’ outcomes even after improvement in hemodynamic status had been achieved. The origin of symptoms in chronic HF (CHF) is not related in a simple manner to hemodynamic findings as well (2). These discoveries led to the for­mulation of the neurohormonal hypothesis of the progression of HF (3). In recent years much has been learned about the pathophysiology of HF, and HF is today regarded as a hemodynamic disorder due to impaired pump function with reduced cardiac output and subsequent venous congestion. Complex neurohormonal activation is aimed at improv­ing the mechanical environment of the heart, and circulating and local hormones as well as proinflammatory cytokines play an important role in disease progression. In fact, in recent years the most important developments in the treatment of HF have been the intro­duction of first the angiotensin converting enzyme (ACE) inhibitors and then ß-blockers, which resulted in an almost 50% decrease in mortality in the last decade in therapeutic trials. The great benefits of these drugs on delaying the progression of HF are mainly attributable to their neurohumoral effects with beneficial effects on the remodeling of the failing heart. This chapter focuses on the complex neurohormonal changes in HF with their diagnostic implications.