• Eiichi Akiyama, Seigo Sugiyama, Yasushi Matsuzawa, Masaaki Konishi, Hiroyuki Suzuki, Toshimitsu Nozaki, Keisuke Ohba, Junichi Matsubara, Hirofumi Maeda, Yoko Horibata, Kenji Sakamoto, Koichi Sugamura, Megumi Yamamuro, Hitoshi Sumida, Koichi Kaikita, Satomi Iwashita, Kunihiko Matsui, Kazuo Kimura, Satoshi Umemura, and Hisao Ogawa.
• Department of Cardiovascular Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
• J. Am. Coll. Cardiol. 2012 Oct 30;60(18):1778-86.

ObjectivesThe purpose of this study was to investigate whether peripheral endothelial dysfunction could predict the occurrence of cardiovascular events in patients with heart failure (HF) with normal left ventricular ejection fraction (HFNEF).BackgroundEndothelial dysfunction plays an important role in HF, but the relation between peripheral endothelial dysfunction and prognosis in HFNEF remains unknown.MethodsWe conducted a prospective cohort study of 321 patients with HFNEF. We evaluated cardiac function by echocardiography measuring the ratio of early transmitral flow velocity to tissue Doppler early diastolic mitral annular velocity (E/e'), noninvasively assessed peripheral endothelial function by reactive hyperemia-peripheral arterial tonometry (RH-PAT) as the RH-PAT index (RHI), and followed cardiovascular events.ResultsA total of 59 patients had a cardiovascular event. Kaplan-Meier analysis demonstrated a significantly higher probability of cardiovascular events in the low RHI group than in the high RHI group (mean follow-up: 20 months; log-rank test: p < 0.001). Multivariate Cox hazard analysis identified RHI (per 0.1) (hazard ratio [HR]: 0.80; 95% confidence interval [CI]: 0.67 to 0.94; p = 0.007), E/e' (Ln[E/e'] [per 0.1]) (HR: 1.15; 95% CI: 1.04 to 1.26; p = 0.006), and B-type natriuretic peptide (BNP) (Ln[BNP] [per picogram/milliliter]) (HR: 1.81; 95% CI: 1.44 to 2.28; p < 0.001) as independent predictors of cardiovascular events. The C-statistics for cardiovascular events substantially increased when the RHI was added to the HFNEF prognostic 5 factors (PF5)-age, diabetes, New York Heart Association classification, HF hospitalization history, and left ventricular ejection fraction-which were identified in the I-PRESERVE (Irbesartan in Heart Failure with Preserved Ejection Fraction Study) (PF5 alone: 0.671; PF5 + RHI: 0.712). The net reclassification index was significant after addition of the RHI (19.0%, p = 0.01).ConclusionsPeripheral endothelial dysfunction independently correlated with future cardiovascular events, adding incremental clinical significance for risk stratification in patients with HFNEF. (Endothelial Dysfunction Assessed by Reactive Hyperemia Peripheral Arterial Tonometry and Heart Failure with Preserved Left Ventricular Ejection Fraction; UMIN000002640).Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

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