MECHANISMS OF EXERCISE LIMITATION IN HYPERTROPHIC CARDIOMYOPATHY

To assess the relation of exercise capacity to indexes of systolic and diastolic function in hypertrophic cardiomyopathy, 81 patients underwent two-dimensional echocardiography, technetium-99m equilibrium radionuclide angiography acquired in list mode and maximal, symptom-limited, treadmill exercise testing with measurement of maximal oxygen consumption (VO2 max). VO2 max for the group was 13.9 to 49.3 (mean 25.4) ml/min per kg. Thirty-six patients (44%) achieved less-than-or-equal-to 70% of age-predicted VO2 max. Patients with such a degree of limitation were more likely to be in New York Heart Association functional class II or III (23 of 36 vs. 14 of 45; p = 0.005); there was no such relation between VO2 and the incidence and magnitude of rest left ventricular outflow tract pressure gradient > 30 mm Hg (11 of 36 vs. 11 of 45; p = NS and 58 +/- 24 vs. 65 +/- 19 mm Hg; p = NS). In the 22 patients with a left ventricular outflow tract gradient, the ratios of peak ejection to peak filling rate and of atrial contribution to left atrial dimension were related to percent of the age-predicted VO2 max (r = 0.49, p = 0.02 and r = 0.54, p < 0.02). These ratios reflect impaired left ventricular systolic performance and atrial systolic failure, respectively. Stepwise discriminant analysis revealed these two ratios to be the two strongest predictors (p = 0.0001) of patients with a left ventricular outflow tract gradient whose VO2 max was less-than-or-equal-to 70% of the age-predicted value (sensitivity 90%, specificity 100%). In 59 patients without a rest left ventricular outflow tract gradient, peak filling rate and time to end-systole were weakly related to the age-predicted VO2 max (r = 0.27, p < 0.05 and r = -0.28, p < 0.05). Stepwise discriminant analysis revealed that in those patients without a left ventricular outflow tract gradient reduced peak filling rate and prolonged time to end-systole best identified (p = 0.004) patients whose VO2 max was less-than-or-equal-to 70% of the age-predicted value (sensitivity 76%, specificity 62%). These findings indicate different mechanisms of exercise limitation in hypertrophic cardiomyopathy. In patients with a left ventricular outflow gradient at rest, the main determinants of exercise limitation were impaired left ventricular and left atrial systolic performance. In those without a gradient, however, diastolic function was a more important factor in the limitation of exercise performance.