Key result
Venous endothelial dysfunction drives HFpEF by increasing venous tone and mean circulatory filling pressure.
Why the study?
Pathophysiological mechanisms in HFpEF remain poorly defined, with the venous system emerging as an underrecognized contributor to pathogenesis via endothelial dysfunction and elevated venous tone.
The venous system and its pharmacological modulation represent an underrecognized but critical target in HFpEF pathogenesis, warranting further preclinical and clinical investigation.
Answers are grounded in this paper and cite their sources.
Venous modulation should not yet alter HFpEF care; leaves open a capacitance target for prospective trials.
Heart failure with preserved ejection fraction (HFpEF) is a major cause of cardiovascular morbidity and mortality globally. Despite significant research, the pathophysiological mechanisms underlying this complex condition remain poorly defined. Recently, the venous system has emerged as an underrecognized yet critical contributor to HFpEF pathogenesis, functioning as the primary capacitance system and a determinant of central venous pressure. Evidence suggests an imbalance between endothelial-derived relaxing and contractile factors (EDRF/EDCF), leading to venous endothelial dysfunction, elevated venous tone, and increased mean circulatory filling pressure, all factors that contribute to ventricular–vascular mismatch. This review synthesizes current literature on the vasoactive effects of EDRF and EDCF in the venous vs. arterial systems, in both preclinical and clinical models, and examines how HFpEF therapies may target these pathways. While preclinical models demonstrate the vasoactivity of these mediators in veins of healthy and hypertensive animals, studies investigating its effects in validated HFpEF models are lacking, prompting further research. Furthermore, clinical studies should also prioritize functional assessments and venous-specific endpoints, including direct measures of venous compliance, to better guide therapeutic strategies for HFpEF.
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Lineham et al. (2026) conducted a review in Heart failure with preserved ejection fraction (HFpEF). Venous endothelial dysfunction and an imbalance in relaxing and contractile factors contribute to HFpEF pathogenesis by increasing venous tone and mean circulatory filling pressure.
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