Author + information
- Received March 20, 2012
- Revision received July 4, 2012
- Accepted July 23, 2012
- Published online October 30, 2012.
- Eiichi Akiyama, MD⁎,†,
- Seigo Sugiyama, MD, PhD⁎,⁎ (, )
- Yasushi Matsuzawa, MD⁎,†,
- Masaaki Konishi, MD, PhD⁎,†,
- Hiroyuki Suzuki, MD†,
- Toshimitsu Nozaki, MD, PhD⁎,
- Keisuke Ohba, MD⁎,
- Junichi Matsubara, MD, PhD⁎,
- Hirofumi Maeda, MD⁎,
- Yoko Horibata, MD⁎,
- Kenji Sakamoto, MD, PhD⁎,
- Koichi Sugamura, MD, PhD⁎,
- Megumi Yamamuro, MD, PhD⁎,
- Hitoshi Sumida, MD, PhD‡,
- Koichi Kaikita, MD, PhD⁎,
- Satomi Iwashita, MT⁎,
- Kunihiko Matsui, MD, MPH§,
- Kazuo Kimura, MD, PhD†,
- Satoshi Umemura, MD, PhD∥ and
- Hisao Ogawa, MD, PhD⁎
- ↵⁎Reprint requests and correspondence:
Dr. Seigo Sugiyama, Department of Cardiovascular Medicine, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku Kumamoto City 860-8556, Japan
Objectives The 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).
Background Endothelial dysfunction plays an important role in HF, but the relation between peripheral endothelial dysfunction and prognosis in HFNEF remains unknown.
Methods We 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.
Results A 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).
Conclusions Peripheral 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)
- endothelial function
- heart failure with normal left ventricular ejection fraction
- reactive hyperemia-peripheral arterial tonometry
Funding: This study was supported in part by a grant-in-aid for Scientific Research (No. C22590786 for S. Sugiyama) from the Ministry of Education, Science, and Culture in Japan. All authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received March 20, 2012.
- Revision received July 4, 2012.
- Accepted July 23, 2012.
- American College of Cardiology Foundation