Prognostic Value of Flow-Mediated Dilation and Reactive Hyperemia Index in Heart Failure: A Systematic Review and Meta-Analysis

<b>Background/Objectives</b>: There is a growing acknowledgment of the role of endothelial dysfunction as an outcome predictor and therapeutic target in heart failure (HF). Flow-mediated dilation (FMD) and the reactive hyperemia index (RHI) are non-invasive diagnostic measures of endothelial dysfunction. In this meta-analysis, we aimed to highlight the importance of endothelial dysfunction, as measured by FMD and RHI, and its association with clinical outcomes, including mortality, hospitalization, and exercise capacity in patients with HF. <b>Methods</b>: We reviewed observational studies assessing clinical outcomes of HF patients with and without impaired FMD and/or RHI. Searches around electronic research databases were conducted using predetermined keywords. Meta-analysis was subsequently performed on selected studies that assessed adverse events in patients with HF. Our primary outcome was adverse events, which include mortality, disease progression, hospitalization, and complications (stroke, myocardial infarction, and heart attack). <b>Results</b>: This review included 16 studies, with a total of 1890 participants. Meta-analysis demonstrated that lower FMD in patients with HF had a significantly higher risk of adverse events (HR 1.44, 95% CI 1.15-1.82; <i>p</i> = 0.002; I² = 80%, random-effects model). In contrast, lower RHI was not associated with an increased risk of adverse events (HR 1.32, 95% CI 0.96-1.82; <i>p</i> = 0.09; I² = 87%, random-effects model). <b>Conclusions</b>: Endothelial dysfunction is associated with adverse endpoints in HF. FMD showed consistent prognostic values, while RHI's prognostic significance is less clear and requires further investigation.