Relation of left ventricular chamber stiffness at rest to exercise capacity in hypertrophic cardiomyopathy

The degree of exercise capacity is poorly predicted by conventional markers of disease severity in patients with hypertrophic cardiomyopathy (HC). The principal mechanism of exercise intolerance in patients with HC is the failure of stroke volume augmentation due to left ventricular (LV) diastolic dysfunction. The role of LV chamber stiffness, assessed noninvasively, as a determinant of exercise tolerance is unknown. Sixty-four patients with HC were studied with Doppler echocardiography, exercise testing, and gadolinium cardiac magnetic resonance. The LV chamber stiffness index was determined as the ratio of pulmonary capillary wedge pressure (derived from the E/Ea ratio) to LV end-diastolic volume (assessed by cardiac magnetic resonance). Maximal exercise tolerance was defined as achieved METs. There were inverse correlations between METs achieved and age (r = -0.38, p = 0.003), heart rate deficit (r = -0.39, p = 0.002), LV outflow tract gradient (r = -0.33, p = 0.009), the E/Ea ratio (r = -0.4, p = 0.001), mean LV wall thickness (r = -0.26, p = 0.04), and LV stiffness (r = -0.56, p <0.001) and a positive correlation between METs achieved and LV end-diastolic volume (r = 0.33, p = 0.01). On multivariate analysis, only LV chamber stiffness was associated with exercise capacity. A LV stiffness level of 0.18 mm Hg/ml had 100% sensitivity and 75% specificity (area under the curve 0.84) for predicting < or =7 METs achieved. In conclusion, LV diastolic dysfunction at rest, as manifested by increased LV chamber stiffness, is a major determinant of maximal exercise capacity in patients with HC.