Author + information
- Received April 15, 2019
- Revision received August 20, 2019
- Accepted August 26, 2019
- Published online November 4, 2019.
- Akira Suda, MD, PhD,
- Jun Takahashi, MD, PhD,
- Kiyotaka Hao, MD, PhD,
- Yoku Kikuchi, MD, PhD,
- Tomohiko Shindo, MD, PhD,
- Shohei Ikeda, MD, PhD,
- Koichi Sato, MD,
- Jun Sugisawa, MD,
- Yasuharu Matsumoto, MD, PhD,
- Satoshi Miyata, PhD,
- Yasuhiko Sakata, MD, PhD and
- Hiroaki Shimokawa, MD, PhD∗ (, )@TohokuUniPR
- ↵∗Address for correspondence:
Dr. Hiroaki Shimokawa, Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, 1-1, Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan.
Background Approximately one-half of patients undergoing diagnostic coronary angiography for angina have no significant coronary stenosis, in whom coronary functional abnormalities could be involved.
Objectives This study examined the significance of coronary functional abnormalities in a comprehensive manner for both epicardial and microvascular coronary arteries in patients with angina and nonobstructive coronary artery disease (CAD).
Methods This study prospectively enrolled 187 consecutive patients (male/female 113/74, 63.2 ± 12.3 years), who underwent acetylcholine provocation test for coronary spasm and measurement of index of microcirculatory resistance (IMR) to evaluate coronary microvascular function, and followed them for a median of 893 days.
Results Of all subjects, acetylcholine test identified 128 patients with vasospastic angina (VSA) (68%), and cardiac events occurred in 10 patients (5.3%) during the follow-up. Multivariable analysis revealed that IMR correlated with the incidence of cardiac events (hazard ratio: 1.05; 95% confidence interval: 1.02 to 1.09; p = 0.002) and receiver-operating characteristics (ROC) curve analysis identified IMR of 18.0 as the optimal cut-off value. Among the 4 groups based on the cut-off value of IMR and the presence of VSA, the Kaplan-Meier survival analysis showed a significantly worse prognosis in the group with high IMR (≥18.0) and VSA compared with other groups (log rank, p = 0.002). Importantly, intracoronary administration of fasudil, a Rho-kinase inhibitor, significantly ameliorated IMR in the VSA patients with increased IMR (p < 0.0001).
Conclusions These results indicate that in patients with angina and nonobstructive CAD, coexistence of epicardial coronary spasm and increased microvascular resistance is associated with worse prognosis, for which Rho-kinase activation may be involved.
This study was supported in part by the grants-in-aid from the Ministry of Education, Culture, Sports, Science, and Technology, Japan. The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received April 15, 2019.
- Revision received August 20, 2019.
- Accepted August 26, 2019.
- 2019 American College of Cardiology Foundation
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