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Project

Cardiac reserve and ventricular interdependence in right heart disease: diagnostic and therapeutic prospects

The cardiovascular system contains two separate circuits, the pulmonary and the systemic circulation, which is paralleled in cardiac anatomy by the division of the heart into a right and a left side. The right heart pumps the deoxygenated blood it receives from the systemic veins into the pulmonary circulation while the left heart then propels the oxygenated blood back into the systemic circulation. Historically, evaluation or cardiac physiology and pathophysiology has focused primarily on left ventricular performance. Nonetheless, proper function of the cardiovascular system requires a concerted effort of both sides because the left and the right heart operate in series and are inextricably linked on an anatomical and functional level. Unsurprisingly, a large body of evidence now firmly establishes the important role of the right ventricular-pulmonary vascular unit in both normal cardiovascular physiology and a broad range of cardiac and pulmonary vascular diseases.

As exercise capacity is an important outcome predictor in cardiovascular disease, evaluation of cardiac function during exercise is of prime clinical relevance. Beyond its prognostic value, cardiac imaging during exercise also provides a unique insight into disease mechanisms as it evaluates patients whilst they are symptomatic. Finally, the assessment of cardiac function during exercise may unmask underlying cardiac dysfunction as in preclinical or early disease stages as compensatory structural and functional changes often mitigate the underlying dysfunction at rest.

Building further upon previous work in this domain by our research group, this thesis focuses on comprehensive exercise imaging techniques to evaluate the diagnostic and therapeutic potential of cardiac reserve and ventricular interdependence in patients with pulmonary vascular disease, heart failure and arrhythmic cardiomyopathy. We examined the cardiac response to exercise and its interaction with the circulation and demonstrated that (1) the pathophysiology of exercise limitation in patients with chronic thromboembolic pulmonary disease is related to both depressed cardiac reserve and abnormal pulmonary vascular response, (2) the multifaceted decline of cardiac and pulmonary vascular function accompanying disease progression in HFpEF is unmasked by exercise and already emerges in preclinical disease, (3) exercise imaging improves discrimination of pathology in arrhythmogenic cardiomyopathy and (4) exercise imaging holds potential in the evaluation of treatment response in pulmonary vascular disease. Furthermore, we described in detail how exercise and respiration augment adverse ventricular interdependence in precapillary pulmonary hypertension and to a lesser extent also in heart failure with preserved ejection fraction. Finally, we explored cardiac pacing as means of reducing adverse ventricular interaction in an experimental ovine model of RV pressure overload.

In conclusion, the findings outlined in this thesis manuscript demonstrate the added clinical benefit of combining exercise with state-of-the-art cardiac imaging and potentially broadens its scope to evaluation of treatment response.

Date:1 Aug 2015 →  14 Dec 2021
Keywords:Pulmonary Hypertension, Right Ventricle, Exercise testing, Cardiac Resynchronisation Therapy, Pulmonary Banding, Cardiac Magnetic Resonance
Disciplines:Cardiac and vascular medicine
Project type:PhD project