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Pressure and volume registration of the right ventricle, during exercise, in patients with pulmonary hypertension.

The degree of RV dysfunction is an important determinant of mortality and exercise capacity in cardiopulmonary disease. Unfortunately, detection of RV dysfunction is most often delayed, when impairment is severe. Early detection could have important clinical implications for the management of these patients. Furthermore, demonstration of RV dysfunction during exercise might help explain symptoms such as exertional dyspnea or exercise intolerance. The aim of our project is to investigate right ventricular function (RV) and central hemodynamics during exercise, using multimodality assessment, in three different settings: (1) familial pulmonary hypertension, (2) heart failure with preserved ejection fraction, (3) unexplained exertional dyspnea after acute pulmonary embolism, and (4) patients with chronic thromboembolic pulmonary hypertension (CTEPH). Our general hypothesis is that in the first three groups, RV dysfunction may be subtle or undetectable at rest, but can be unmasked under the stress of incremental cycling exercise and the resulting increase in PAP, and that RV dysfunction can be an important and underrecognized cause of exercise limitation. In addition, the fourth group consists of patients with established pulmonary hypertension at rest (CTEPH), which represents the extreme spectrum of pulmonary vascular disease against which the other study groups can be compared. Finally, we have used the same multimodality assessment in a cohort of healthy athletes and non-athletic subjects to accurately describe RV and pulmonary vascular physiology during exercise in healthy individuals. Therefore, the exercise response in the different study populations can also be compared with normal physiology. To evaluate our hypotheses we need to accurately assess RV function during exercise. This requires simultaneous assessment of heart muscle contractility and the load against which it must work. We have developed a new methodology combining real-time cardiac magnetic resonance (CMR) and invasive pressure measures for a comprehensive description of the RVpulmonary arterial unit by providing simultaneous pressure/volume information at rest and during exercise. The testing involved is the most comprehensive in this field of research to date and is only available in a few centers around the world. Our method therefore involves catheter measurement of intra-cardiac pressures and simultaneous assessment of volumes and contractility by CMR and echocardiography – all performed with the study subject at rest and then with exercise. To modulate the load on the RV further, inhalation of oxygen reduced air and sildenafil citrate will be used to augment and attenuate increases in pulmonary artery pressure. This project has the potential to enhance the current understanding of RV function in patients with pulmonary hypertension and to provide a sensitive and accurate tool for diagnosis. This may lead to earlier diagnosis, treatment and better outcomes in these patients.

Date:1 Jan 2014 →  31 Dec 2017
Keywords:Pulmonary hypertension
Disciplines:Laboratory medicine, Palliative care and end-of-life care, Regenerative medicine, Other basic sciences, Other health sciences, Nursing, Other paramedical sciences, Other translational sciences, Other medical and health sciences