Exercise intolerance in patients with heart failure and preserved left ventricular systolic function: failure of the Frank-Starling mechanism 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 demonstrates 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 less than 0.001), primarily due to a 41% reduction in peak cardiac index (4.2 +/- 1.4 versus 7.1 +/- 1.1 liters/min per m2; p less than 0.001). In patients compared with normal subjects, peak left ventricular stroke volume index (34 +/- 9 versus 46 +/- 7 ml/min per m2; p less than 0.01) and end-diastolic volume index (56 +/- 14 versus 68 +/- 12 ml/min per m2; p less than 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 less than 0.0001) and cardiac index (r = 0.80; p less than 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 less than 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. 