Content area
Full Text
Abstract
Heart failure is a common form of heart disease associated with progressive exercise intolerance and high risk of adverse clinical outcome events. The pathophysiology of chronic systolic heart failure is fundamentally determined by the failure of the circulatory system to deliver oxygen sufficient for metabolic needs, and it is best explained by a complex interplay between intrinsic abnormalities of ventricular pump function and extracardiac factors that limit oxygen use in metabolically active tissues. This brief review highlights the role of extracardiac factors (peripheral factors) that may impact exercise capacity in patients with chronic systolic heart failure. Reduced metabolic vasodilation limits delivery of available cardiac output reserve to skeletal muscle during exercise, and it is associated with reduced peak oxygen capacity. Abnormal substrate use in skeletal muscle due to reduced skeletal muscle mass, change in skeletal muscle fiber type, and mitochondrial dysfunction reduces work efficiency and submaximal exercise endurance capacity in patients with systolic heart failure. These extracardiac peripheral mechanisms of impaired exercise tolerance in chronic heart failure may be targets for novel therapeutic development in this patient population.
Keywords: vasodilation; skeletal muscle; exercise
Heart failure affects 6 million persons in the United States and is associated with high rates of hospitalization (1.1 million/yr), high health care costs (>$30 billion/yr in Medicare costs), and high mortality risk (30 to 50% over 5 yr) (1, 2). Heart failure due primarily to systolic dysfunction (also known as heart failure with reduced ejection) accounts for approximately 50% of the heart failure cases. Although there is some overlap in the pathophysiology of heart failure related to primary systolic or diastolic dysfunction, this review is focused on a discussion of chronic systolic heart failure. The pathophysiology of chronic systolic heart failure is fundamentally determined by the failure of the circulatory system to deliver sufficient oxygen for metabolic needs, and it is best explained by a complex interplay between intrinsic abnormalities of ventricular pump function and extracardiac factors that limit oxygen use in metabolically active tissues (3-6). Exercise intolerance at both maximal and submaximal effort is the hallmark of progressive heart failure, and it is associated with worsened quality of life and increased risk of adverse clinical outcomes. This brief review considers the role of two extracardiac factors ("peripheral factors")-...