Determinants of exercise capacity and prognosis in dilated cardiomyopathy : contribution of left ventricular diastolic function and mitral regurgitation

This original work aimed to further evaluate the central cardiac determinants of exercise capacity impatients with dilated cardiomyopathy (DCM) and chronic heart failure (CHF), namely the relative contribution of left ventricular (LV) diastolic filling and mitral regurgitation (MR) and their prognostic relevance. Indeed, the present thesis issue not only provides a more robust definition on the relationship, between diastolic filling and exercise capacity as well as the pathophysiological basis of exercise impairment in CHF, but also allowed an appropriate prognostic stratification of patients involved with this disorder. We first examined in a more quantitative way the potential relationship between indices of diastolic filling and systolic function (assessed by Doppler echocardiography and radionuclide ventriculography) and exercise capacity (quantitatively determined as total body peak oxygen uptake or peak VO2 during a symptom-limited bycicle or treadmill exercise). We also evaluated the robustness of these measurements in terms of reproducibility of our findings, the effects of postural changes and mode of exercise on these possible relationships between LV diastolic filling indices (namely the E/A ratio) and exercise data (peak VO2). The data indicate that indices of diastolic filling rather than systolic function were independent explanators of peak VO2. Since they also supported the existence of an independent contribution of the severity of MR to peak VO2, we then attempted to define the exact mechanisms responsible for the observed relationship. The present study is the first indication that exercise-induced changes in the severity of MR limit stroke volume adaptation during exercise, and could therefore contribute to limit exercise capacity in patients with DCM and chronic low-output heart failure. Because these indices were strongly correlated with exercise capacity, which is a powerful prognostic indicator, our second goal was to determine their prognostic information. A prognostic study was then conducted in a large cohort of consecutive patients with DMC of ischemic and non-ischemic origin. During t a long mean follow-up of 62 months, we found that these indices were independently associated with the risk of cardiac events (cardiac death or the need for heart transplantation) related to this disorder irrespective of the etiology. Based on clinical and echocardiographic parameters identified by the Cox analyses, a risk score was elaborated, and allowed appropriate classification of individual patients into risk group (to die or to require heart transplantation). The data indicate thus that the prognostic of these patients is strikingly related to the degree of residual LV diastolic performance. In conclusion, the assessment of LV diastolic filling provides comprehensive information of the filling pressures, the exercise capacity, and the prognosis in patients with DCM. Doppler-derived LV filling pattern, namely E/A ratio, is particularly appealing because it is easy to measure, readily available for daily clinical decision making without any risk for the patient. Closely related to VO2, E/A ratio which is measured at rest may reliably predict exercise capacity and prognosisThèse de doctorat en sciences biomédicales (cardiologie) -- UCL, 199