Right Ventricular Dysfunction and Ventriculo‐Arterial Uncoupling in Heart Failure With Preserved Ejection Fraction: A Phenotype‐Specific Review of Mechanisms, Diagnosis, and Therapeutic Strategies
Amarelle Chamoun, Talha Farooq, Suhayya Batool, Sadia Tameez‐ud—din, Muhammad Yousaf, Preet Memon, Mohsin Ali, Arun Kumar Maloth, F. N. U. Sawaira, Muhammad Taimur Khan, Mohammad Eisa Ali, Mansoor Khalid, Maleeha Pandit, Kamil Ahmad KamilABSTRACT
Background
Heart failure with preserved ejection fraction (HFpEF) accounts for nearly half of all global heart failure cases. Historically viewed as a left‐centric diastolic disorder, emerging evidence identifies right ventricular (RV) dysfunction and impaired ventriculo‐arterial (RV‐PA) coupling as central drivers of exercise intolerance, functional decline, and adverse clinical outcomes.
Objectives
This review synthesizes current evidence on the pathophysiological mechanisms, advanced diagnostic modalities, prognostic implications, and phenotype‐specific therapies for RV dysfunction in HFpEF, advocating for a transition to systematic biventricular evaluation.
Methods
A structured, PRISMA‐informed search of PubMed and Scopus (2015–2024) identified 74 eligible studies evaluating RV structure, function, and hemodynamics in HFpEF cohorts.
Results
RV dysfunction is prevalent in 19% to 33% of HFpEF patients and independently predicts all‐cause mortality and heart failure hospitalizations. Key pathophysiological drivers include post‐capillary pulmonary hypertension, impaired RV lusitropy, systemic inflammation, and inter‐ventricular dependence. Non‐invasive markers notably speckle‐tracking echocardiography, 4D‐flow cardiac magnetic resonance (CMR), and the TAPSE/PASP ratio enable early identification of subclinical RV‐PA uncoupling. While traditional heart failure therapies show limited efficacy, emerging options including SGLT2 inhibitors, interatrial shunt devices, GLP‐1 receptor agonists, and targeted pulmonary vasodilators demonstrate potential to preserve RV strain and restore hemodynamics across distinct clinical phenotypes.
Conclusions
RV dysfunction is a major prognostic marker in HFpEF. Routine inclusion of RV‐PA coupling indices in diagnostic and risk‐stratification algorithms is essential to guide precision‐based, phenotype‐guided management and improve clinical trajectories.