Clinical assessment of endothelial function in heart failure with preserved ejection fraction: A meta-analysis with meta-regressions

Background: Endothelial dysfunction is a key mechanism in the development of cardiac remodelling and diastolic dysfunction in heart failure with preserved ejection fraction (HFpEF). Flow-mediated (FMD) and nitrate-mediated dilation (NMD) are noninvasive methods to assess endothelial function. We performed a meta-analysis evaluating the impact of HFpEF on FMD and NMD. Methods: PubMed, Web of Science, Scopus and EMBASE databases were systematically searched according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Differences were expressed as mean difference (MD) with 95% confidence intervals (95%CI). The random effects method was used. Results: A total of seven studies were included in the final analysis, 7 with data on FMD (326 HFpEF patients and 417 controls) and 3 on NMD (185 HFpEF patients and 271 controls). Compared to controls, HFpEF patients showed significantly lower FMD (MD: −1.929; 95%CI: −2.770, −1.088; P <.0001) and NMD values (MD: −2.795; 95%CI: −3.876, −1.715; P <.0001). Sensitivity analyses substantially confirmed results. Meta-regression models showed that increasing differences in E/A ratio (Z-score: −2.002; P =.045), E/E’ ratio (Z-score: −2.181; P =.029) and left atrial diameter (Z-score: −1.951; P =.050) were linked to higher differences in FMD values between cases and controls. Conclusions: Impaired endothelial function can be documented in HFpEF, with the possibility of a direct association between the severity of diastolic and endothelial dysfunction. Targeting endothelial dysfunction through pharmacological and rehabilitation strategies may represent an attractive therapeutic option.