Relation of diastolic function and exercise capacity in ischemic left ventricular dysfunction: Role of β-agonists and β-antagonists

The relation between global left ventricular function at rest (evaluated during cardiac catheterization) and exercise capacity was examined in a group of 33 untreated patients with a previous anterior myocardial infarction. The resting ejection fraction (range, 24-68%) correlated poorly with exercise duration (r = 0.47) and did not separate patients with a depressed exercise capacity (exercise duration < 500 seconds: group A, n = 18) from patients with preserved exercise tolerance (group B, n = 15). The resting left ventricular end-diastolic and end-systolic volume indexes were comparable in groups A and B, but the diastolic pressure-volume relation was shifted upward, and the mean left ventricular pressure during diastolic filling was higher in group A than in group B (19 ± 8 versus 14 ± 4 mmHg; p < 0.02). The heart rate at maximal exercise was similar in both groups (160 ± 16 versus 160 ± 17 beats/min; NS), but heart rate was higher at any given level of exercise in group A than in group B. When 12 patients of group A were treated with xamoterol, a β₁-adrenoceptor partial agonist, their exercise duration increased by 20 ± 14% (p < 0.001), and their maximal exercise heart rate decreased from 158 ± 16 to 143 ± 11 beats/min (p < 0.001). This improved exercise capacity was accompanied by a downward shift of the resting diastolic left ventricular pressure-volume relation and by a decrease in mean left ventricular pressure during diastolic filling. None of these variables changed significantly in six patients of group A treated with placebo. In conclusion, abnormalities of left ventricular diastolic distensibility are present at rest in patients with reduced exercise capacity and ischemic left ventricular dysfunction, and the presence of these abnormalities may predict exercise tolerance better than the indexes of systolic function. These observations suggest that left ventricular diastolic function is an important determinant of functional capacity in patients with chronic heart failure and that exercise tolerance may be improved by drugs (e.g., partial β-agonists) that produce a favorable shift in left ventricular diastolic distensibility.