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BACKGROUND:The various conditions causing a chronic increase of RV pressure greatly differ in the occurrence of RV failure, and in clinical outcome. To get a better understanding of the differences in outcome, RV remodeling, longitudinal function, and transverse function are compared between patients with pulmonary stenosis (PS), those with a systemic RV and those with pulmonary hypertension (PH). MATERIALS AND METHODS:This cross-sectional study prospectively enrolled subjects for cardiac magnetic resonance imaging (CMR), functional echocardiography and cardiopulmonary exercise testing. The study included: controls (n = 37), patients with PS (n = 15), systemic RV (n = 19) and PH (n = 20). Statistical analysis was performed using Analysis of Variance (ANOVA) with posthoc Bonferroni. RESULTS:PS patients had smaller RV volumes with higher RV ejection fraction (61.1±9.6%; p

BACKGROUND:Pulmonary arterial hypertension is usually fatal due to right ventricular failure and is frequently associated with co-existing left ventricular dysfunction. Endothelin-1 is a powerful pro-fibrotic mediator and vasoconstrictor that is elevated in pulmonary arterial hypertension. Endothelin receptor blockers are commonly used as pulmonary vasodilators, however their effect on biventricular injury, remodeling and function, despite elevated isolated right ventricular afterload is unknown. METHODS:Elevated right ventricular afterload was induced by progressive pulmonary artery banding. Seven rabbits underwent pulmonary artery banding without macitentan; 13 received pulmonary artery banding + macitentan; and 5 did not undergo inflation of the pulmonary artery band (sham-operated controls). RESULTS:Right and left ventricular collagen content was increased with pulmonary artery banding compared to sham-operated controls and ameliorated by macitentan. Right ventricular fibrosis signaling (connective tissue growth factor and endothelin-1 protein levels); extra-cellular matrix remodeling (matrix-metalloproteinases 2 and 9), apoptosis and apoptosis-related peptides (caspases 3 and 8) were increased with pulmonary artery banding compared with sham-operated controls and decreased with macitentan. CONCLUSION:Isolated right ventricular afterload causes biventricular fibrosis, right ventricular apoptosis and extra cellular matrix remodeling, mediated by up-regulation of endothelin-1 and connective tissue growth factor signaling. These pathological changes are ameliorated by dual endothelin receptor blockade despite persistent elevated right ventricular afterload.