Exploring the Mechanisms of Exercise Intolerance in Patients With HFpEF: Are We too "Cardiocentric?".

D espite having a normal left ventricular ejection fraction, patients with heart failure with preserved ejection fraction (HFpEF) have limited exercise capacity, represented by a peak oxygen consumption (VO2) that is less than what would be predicted for age, and comorbidities including obesity, metabolic syndrome, diabetes, or hypertension. Exercise intolerance is their main symptom, even when fluid balance, systemic blood pressure, and heart rate are optimized. In addition to a reduction in quality of life, reduced peak VO2 in these patients has also been shown to determine prognosis. Knowledge of the physiological factors that limit exercise capacity in these patients may result in approaches to improve functional capacity and perhaps alter the natural history of the syndrome. There is no doubt that reductions in cardiac output and inappropriate increases in cardiac filling pressures contribute to reduced exercise capacity in patients with HFpEF. Reports by various investigators have demonstrated chronotropic incompetence (1), alterations in diastolic function with exaggerated filling pressures during exercise (2), reductions in cardiac output during exercise (3), and abnormalities in ventricular-arterial coupling (4) in these patients. Despite these central cardiac abnormalities, several studies have shown that only 60% of the reduction in peak VO2 can be explained by a reduction in cardiac output. Patients with HFpEF also have impaired