Right Ventricular Dysfunction and Ventriculo-Arterial Uncoupling in Heart Failure With Preserved Ejection Fraction: A Phenotype-Specific Review of Mechanisms, Diagnosis, and Therapeutic Strategies

Scritto il 31/10/2026
da Amarelle Chamoun

Clin Cardiol. 2026 Nov;49(11):e70489. doi: 10.1002/clc.70489.

ABSTRACT

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.

PMID:42965400 | DOI:10.1002/clc.70489