Exercise Hemodynamics in Chronic Heart Failure: Physiological and Clinical Aspects

Chronic heart failure is intrinsically associated with exercise intolerance. Understanding the pathophysiological background of exercise intolerance is essential for optimizing the response to current and future therapies aiming at an improvement of exercise capacity. Each step in the oxygen transport chain and the rate of oxygen utilization can be responsible for the reduced exercise capacity in CHF patients. In this thesis, additional physiological insight is provided by characterizing central and peripheral determinants of oxygen uptake during (sub)maximal exercise and recovery. In addition, the clinical effects and its underlying mechanisms of high-intensity interval training (HIT) with or without cardiac resynchronization therapy (CRT) were explored. In conclusion, in part I (physiological aspects) we demonstrated physiological heterogeneity during maximal exercise, submaximal exercise and recovery after maximal exercise. Additional insight in the pathophysiology of exercise intolerance in CHF is essential for developing novel therapies. Moreover, characterization of the nature of exercise limitations is needed to ascertain which determinant should be primarily targeted for therapy. We investigated several new exercise related parameters (Q patterns, ratio of Q-to-VO2, SmO2 amplitude and OP relative recovery) that can be used to identify the main limitation. Further research is necessary to explore the clinical usefulness and prognostic significance of these novel approaches. In part II (clinical aspects), we evaluated HIT induced effects on exercise capacity and its physiological determinants in CHF patients with or without CRT. Although we observed benefits at a group level of several maximal and submaximal exercise parameters, there was still a considerable variation between individual patients. In future studies, the clinical and physiological profile of a responder to both CRT and exercise training should be clarified to enable a more tailored therapeutic approach. A prediction model with exercise related parameters such as proposed in this thesis could optimize benefits for individual patients and may lead to lower healthcare costs.