Top Things to Know: Advanced Molecular, Metabolic, and Imaging Approaches to Characterizing Right
Prepared by Soni S. Pullamsetti, PhD
- Right ventricular (RV) dysfunction is a key determinant of outcomes in pulmonary hypertension (PH) and is increasingly recognized in other conditions, including heart failure with preserved ejection fraction (HFpEF), congenital heart disease, cardiomyopathies, acute infection, critical illness, and after left ventricular assist device implantation.
- In PH, chronic pressure overload can progress from adaptive RV hypertrophy to maladaptive remodeling, characterized by RV dilation, fibrosis, stiffness, and RV–pulmonary artery (PA) uncoupling.
- RV afterload is multifactorial, reflecting not only pulmonary vascular resistance but also pulmonary arterial compliance, characteristic impedance, and pulsatile load.
- RV–PA coupling is fundamental to RV performance, and deterioration in coupling indicates the transition to RV failure when contractility can no longer match afterload.
- Loss of RV–PA coupling has significant clinical consequences, including reduced stroke volume, elevated right-sided filling pressures, impaired perfusion, and venous congestion.
- Therapeutic strategies are increasingly shifting toward RV–targeted approaches, such as modulation of inflammation, fibrosis, metabolism, and RV–PA coupling, highlighting the need for RV–specific endpoints in clinical trials.
- Inflammation directly contributes to RV dysfunction, as cytokine activation and immune cell recruitment are associated with disease severity and promote maladaptive remodeling.
- Fibrosis is a major contributor to RV stiffening and functional decline, with pathways such as transforming growth factor (TGF)-β signaling, extracellular matrix remodeling, and integrin biology representing actionable targets.
- Metabolic remodeling is a hallmark of maladaptive RV failure, involving mitochondrial dysfunction, increased glycolysis, oxidative stress, and lipid accumulation, all of which impair RV energetics.
- Future progress in RV failure will depend on integrated precision phenotyping that combines advanced imaging, circulating biomarkers, multi-omics approaches, artificial intelligence, and machine learning to enable earlier detection and personalized therapy.
Citation
Pullamsetti SS, Vanderpool RR, de Man F, de Jesus Perez VA, Hemnes AR, Mukherjee M, Mercer-Rosa L, Spiekerkoetter E, Tello K, Bonnet S; on behalf of the Council on Cardiopulmonary, Critical Care, Perioperative, and Resuscitation; Council on Clinical Cardiology; and Council on Cardiovascular Surgery and Anesthesia. Advanced molecular, metabolic, and imaging approaches to characterizing right ventricular failure: a scientific statement from the American Heart Association. Circulation. Published online April 2, 2026. doi: 10.1161/CIR.0000000000001422