Vascular Dysfunction Predicts Future Deterioration of Left Ventricular Ejection Fraction in Patients with Heart Failure With Mid-Range Ejection Fraction

Background: Deterioration of left ventricular ejection fraction (LVEF) in patients with heart failure with mid-range ejection fraction (HFmrEF) increases mortality and/or HF hospitalization. The purpose of this study was to evaluate whether HFmrEF is associated with vascular dysfunction and whether vascular function predicts future deterioration of LVEF in patients with HFmrEF. Methods: This study was a single-center, retrospective longitudinal cohort study. We evaluated endothelial function assessed by flow-mediated vasodilation (FMD) and vascular smooth muscle function assessed by nitroglycerine-induced vasodilation (NID) in 69 patients with HFmrEF and 426 patients without HF and evaluated the initial deterioration of LVEF defined as LVEF measurement of at least 40% in 39 patients with HFmrEF for up to 3 years. Findings: Both FMD and NID were significantly lower in patients with HFmrEF than in patients without HF. We categorized patients into two groups based on low tertiles of NID: a low group (NID of <7.0%) and an intermediated and high group (NID of ≥7.0%). There were significant differences between the Kaplan-Meier curves for the deterioration of LVEF in the two groups (P <0.01). Multivariate Cox proportional hazard analysis revealed that NID of <7.0% was an independent predictor of future deterioration of LVEF in patients with HFmrEF. Interpretation: Both endothelial function and vascular smooth muscle function are impaired in patients with HFmrEF compared with those in patients without HF and that low NID of <7.0% predicts future deterioration of LVEF. Trial Registration Details: URL for Clinical Trial: http://www.umin.ac.jp/ctr/index.htm Registration Number for Clinical Trial: UMIN000003409. Funding Information: This study was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science and Culture of Japan (18590815 and 21590898 to Higashi). Declaration of Interests: The authors declared that they do not have anything to disclose regarding conflict of interest with respect to this manuscript. Ethics Approval Statement: The Ethics Review Board of Hiroshima University approved the study protocol. Written informed consent for participation in the study was obtained from all of the subjects.