Advanced Molecular, Metabolic, and Imaging Approaches to Characterizing Right Ventricular Failur

02 Apr 20264 min read0 viewsJournal Feed

GIST (Key Takeaways)

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

Right ventricular (RV) dysfunction is a major determinant of outcomes in pulmonary hypertension (PH) and is identified as a primary contributor to morbidity and mortality in this setting.
The disease trajectory involves progressive increases in pulmonary vascular resistance that impose chronic pressure overload on the RV, ultimately contributing to right heart failure, the leading cause of death in advanced PH.
Recognizing RV dysfunction extends beyond PH to broader cardiovascular contexts, including heart failure with preserved ejection fraction, congenital heart disease, COVID-19, and complications after left ventricular assist device implantation.

The RV initially adapts through hypertrophic remodeling aimed at preserving cardiac output under rising afterload.
Over time, adaptive remodeling evolves into maladaptive changes characterized by RV dilation, fibrosis, stiffness, and detachment from the pulmonary circulation, a phenomenon described as RV–pulmonary arterial uncoupling.
Uncoupling signals an inability of the RV to sustain contractile performance against elevated afterload, contributing to progressive RV failure.

Research highlights inflammatory processes and altered cellular signaling as contributors to RV failure.
Molecular, metabolic, and hemodynamic drivers are active areas of investigation to delineate pathways that promote maladaptive remodeling.

Advances in imaging modalities and biomarker discovery are enhancing detection of deleterious RV remodeling.
Emerging therapeutic strategies, including activin signaling inhibition with sotatercept, show potential to lower pulmonary vascular resistance and support RV recovery, though evidence remains to be fully established.