Right ventricular dysfunction is a key predictor of outcomes in pulmonary hypertension and a major contributor to morbidity and mortality as disease progresses. Chronic elevation of pulmonary vascular resistance imposes pressure overload on the right ventricle, which initially adapts via hypertrophic remodeling to preserve output.
Over time, this shifts to maladaptive remodeling characterized by RV dilation, fibrosis, stiffness, and decoupling from the pulmonary artery, termed RV–pulmonary arterial uncoupling. This uncoupling reflects impaired RV contractility against increased afterload and ultimately progresses to right heart failure, the leading cause of death in late-stage PH.
RV dysfunction is increasingly recognized in other systemic conditions, including heart failure with preserved ejection fraction, congenital heart disease, COVID-19, and complications after left ventricular assist device implantation. Research aims to elucidate molecular and hemodynamic drivers of RV failure, such as inflammation and altered signaling, while innovations in imaging and biomarkers enhance detection of maladaptive remodeling.
Therapeutically, approaches like the activin signaling inhibitor sotatercept show potential to reduce pulmonary vascular resistance and aid RV recovery.
Right ventricular failure in pulmonary hypertension: a mechanistic and translational overview