Exercise intolerance in patients with heart failure and preserved left ventricular systolic function: Failure of the Frank-Starling mechanism

Abstract

Invasive cardiopulmonary exercise testing was performed in 7 patients who presented with congestive heart failure, normal left ventricular ejection fraction and no significant coronary or valvular heart disease and in 10 age-matched normal subjects. Compared with the normal subjects, patients demonstrated severe exercise intolerance with a 48% reduction in peak oxygen consumption (11.6 ± 4.0 versus 22.7 ± 6.1 ml/kg per min; p < 0.001), primarily due to a 41% reduction in peak cardiac index (4.2 ± 1.4 versus 7.1 ± 1.1 liters/mm per m2; p < 0.001).In patients compared with normal subjects, peak left ventricular stroke volume index (34 ±9 versus 46 ± 7 ml/min per m2; p < 0.01) and end-diastolic volume index (56 ± 14 versus 68 ± 12 ml/min per m2; p < 0.08) were reduced, whereas peak ejection fraction and end-systolic volume index were not different. In patients, the change in end-diastolic volume index during exercise correlated strongly with the change in stroke volume index (r = 0.97; p < 0.0001) and cardiac index (r = 0.80; p < 0.03). Pulmonary wedge pressure was markedly increased at peak exercise in patients compared with normal subjects (25.7 ± 9.1 versus 7.1 ± 4.4 mm Hg; p < 0.0001). Patients demonstrated a shift of the left ventricular end-diastolic pressure-volume relation upward and to the left at rest. Increases in left ventricular filling pressure during exercise were not accompanied by increases in end-diastolic volume, indicating a limitation to left ventricular filling.These data suggest that abnormalities in left ventricular diastolic function limited the patients' ability to augment stroke volume by means of the Frank-Starling mechanism, resulting in severe exercise intolerance. These findings provide a pathophysiologic rationale for symptoms of chronic fatigue and dyspnea on exertion, which are often present in patients with a history of congestive heart failure and preserved systolic function.