Focus on Coronary Physiology
Effect of Sex Difference of Coronary Microvascular Dysfunction on Long-Term Outcomes in Deferred Lesions

https://doi.org/10.1016/j.jcin.2020.04.002Get rights and content
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Abstract

Objectives

This study investigated the sex difference of long-term cardiovascular outcomes on coronary flow reserve (CFR) and index of microcirculatory resistance (IMR) in patients with deferred coronary artery lesions.

Background

Coronary microvascular dysfunction is associated with poorer long-term outcomes. It can be assessed by CFR and the IMR.

Methods

The study prospectively enrolled 434 patients (133 women and 301 men) and analyzed CFR, IMR, fractional flow reserve, and quantitative coronary angiography. Clinical outcomes were assessed by major adverse cardiovascular event(s) (MACE) of cardiac death, myocardial infarction, and revascularization during 5 years of follow-up. The study protocol was approved by the Institutional Review Board or Ethics Committee at each participating center, and all patients provided written informed consent. The study protocol was in accordance with the Declaration of Helsinki.

Results

Women had milder epicardial disease compared with men (fractional flow reserve: 0.91 [interquartile range (IQR): 0.87 to 0.96] vs. 0.90 [IQR: 0.86 to 0.95]; p = 0.037). IMR was similar between the sexes, but CFR was lower in women (2.69 [IQR: 2.08 to 3.90] vs. 3.20 [IQR: 2.20 to 4.31]; p = 0.006) due to a shorter resting mean transit time, whereas hyperemic mean transit times were similar. At 5-year follow-up, MACE was significantly lower in women compared with men (1.1% vs. 5.5%; p = 0.017). Sex, diabetes mellitus, and CFR were independent predictors for MACE for all patients. The risk of MACE was significantly higher in men with low versus high CFR (hazard ratio: 4.58; 95% confidence interval: 1.85 to 11.30; p = 0.011) which was not seen in women.

Conclusions

There was no sex difference in microvascular function by IMR. CFR was lower in women due to a higher resting coronary flow; however, long-term clinical outcomes in deferred lesions were better in women compared with men. (Clinical, Physiological and Prognostic Implication of Microvascular Status; NCT02186093).

Key Words

coronary artery disease
coronary flow reserve
fractional flow reserve
index of microcirculatory resistance
microvascular function

Abbreviations and Acronyms

CAD
coronary artery disease
CFR
coronary flow reserve
CI
confidence interval
CMD
coronary microvascular dysfunction
FFR
fractional flow reserve
HR
hazard ratio
hTmn
hyperemic mean transit time
IMR
index of microcirculatory resistance
MACE
major adverse cardiovascular event(s)
MI
myocardial infarction
rTmn
resting mean transit time

Cited by (0)

This study was supported by an unrestricted research grant from St. Jude Medical and the National Research Foundation of Korea (grant NRF–2018R1D1A1B07044528). Dr. Koo has received institutional research grant support from St. Jude Medical, Abbott, and Philips. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Cardiovascular Interventions author instructions page.

Drs. Chung and K.E. Lee contributed equally to this work.