Brief Overview of Heart Failure

Heart failure is a varied clinical syndrome with a complex pathophysiology that is still being defined. These features have led to demanding therapeutic regimens that have made optimal management of heart failure a difficult enterprise. In addition, heart failure is common, and its public heath consequences are ever growing. An estimated 4.8 million individuals are afflicted with this syndrome in the United States today, and 400,000 to 700,000 new cases are estimated to develop each year. The prevalence of heart failure increases with age; it approaches 10% of Americans in the ninth decade of life. Aging of the population and the prolonged survival of patients with a variety of cardiovascular diseases that culminate in ventricular dysfunction ensure that the magnitude of the heart failure problem will substantially worsen in the next decade.

Experts have projected a 2- to 3-fold increase in prevalence. In addition to being a common condition, heart failure causes substantial morbidity with total hospitalizations, directly and indirectly related, exceeding three million per year.

This condition directly or indirectly contributes to the death of approximately 250,000 individuals a year. Advanced heart failure remains one of the most disabling and lethal medical conditions. Readmission shortly after hospital discharge remains disturbingly common, and most patients continue to experience limiting symptoms and often poor quality of life despite treatment. The economic burden of the syndrome is staggering, with estimated direct medical expenditures in excess of $20 billion per year.

Definition and Pathophysiology

Heart failure remains the final common pathway for many cardiovascular diseases whose natural history results in symptomatic or asymptomatic left ventricular dysfunction. Although left ventricular diastolic dysfunction is an important part of the clinical spectrum of heart failure, our review will be restricted to patients with left ventricular systolic dysfunction. This condition is accompanied by a number of pathophysiological abnormalities, including structural remodeling and dilation of the left ventricular chamber; reduced myocyte shortening and wall motion; sodium retention and circulatory congestion; systemic vasoconstriction and vascular remodeling that increases impedance of left ventricular ejection; and neurohormonal activation that contributes to many of the above pathophysiological events.

A number of basic and clinical investigations have highlighted the major importance of the renin-angiotensin-aldosterone system (RAAS) in the generation and progression of heart failure.

The traditional pharmacological means of blocking the activity of the RAAS has been through the inhibition of angiotensin-converting enzyme (ACE), which limits the production of angiotensin II, the major active biological peptide of this system. ACE inhibitors initially were viewed as "vasodilator" therapy because of their ability to reverse smooth muscle vasoconstriction in peripheral arterioles and, thus, substantially lower the elevated systemic vascular resistance that contributes to hemodynamic decompensation in heart failure.