Determinants of exercise capacity in patients with coronary artery disease and mild to moderate systolic dysfunction: Role of heart rate and diastolic filling abnormalities

BACKGROUND: To test the hypothesis that diastolic filling abnormalities are an important cause of exercise limitation in some patients with coronary artery disease we assessed the factors limiting exercise capacity in a group of patients with coronary artery disease in whom exercise limitation was greater than expected from the degree of resting left ventricular systolic dysfunction. METHODS AND RESULTS: We assessed the relationship between exercise capacity (maximal oxygen consumption) during erect cycle ergometry, heart rate, radionuclide indices of left ventricular systolic function (ejection fraction) and diastolic filling (peak filling rate, and time to peak filling) during semi-erect cycle ergometry in 20 patients (15 male, five female) who were aged 42-72 years (mean 61 years) and had angiographically proven coronary artery disease and evidence of reversible myocardial ischaemia on thallium scintigraphy. All patients exhibited marked exercise limitation (maximal oxygen consumption 8.7- 22.4 ml.min-1.kg-1--mean 15.9 ml.kg-1.min-1, which was 61.1 +/- 16% of age and gender predicted maximum) due to breathlessness or fatigue rather than angina, in spite of a mean ejection fraction for the group of 46.5% (range 30-67%). We also compared the diastolic filling characteristics of these patients during exercise with 10 healthy controls (age 38-66, mean 58 years; eight male, two female). Comparing diastolic filling characteristics, peak filling rate was higher and time to peak filling shorter both at rest and at peak exercise in controls than patients (peak filling rate 3.1 +/- 0.5 vs 2.2 +/- 0.9 EDV.s-1, P = 0.01 at rest and 8.3 +/- 0.8 vs 5.2 +/- 1.9 EDV.s-1, P < 0.0001 on exercise; time to peak filling 115.2 +/- 29.8 vs 228.9 +/- 71.7 ms, P < 0.0001 at rest and 52.8 +/- 16.2 vs 139.6 +/- 44.8 ms, P < 0.0001 on exercise respectively). On univariate analysis in the patients studied, maximal oxygen consumption was correlated with peak heart rate (r = 0.45 P = 0.04), peak exercise time to peak filling (r = -0.85 P < 0.0001), peak exercise peak filling time rate (r = 0.51 P = 0.019), and the relative increase in cardiac output i.e. cardiac output peak/cardiac output rest (r = 0.58, P = 0.008). There was no correlation between maximal oxygen consumption and resting indices of diastolic filling (peak filling rate and time to peak filling) or with resting or peak exercise ejection fraction. On multiple regression analysis, only peak exercise time to peak filling was significantly related to maximal oxygen consumption. CONCLUSION: We have observed a strong correlation between exercise capacity and indices of exercise left ventricular diastolic filling, and have confirmed previous studies showing a poor correlation with resting and exercise indices of systolic function and resting diastolic filling, in patients with coronary artery disease.