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Coronary Functional Abnormalities in Patients With Angina and Nonobstructive Coronary Artery Disease

Akira Suda¹, Jun Takahashi¹, Kiyotaka Hao¹

¹Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.

Journal of the American College of Cardiology

|November 9, 2019

Insights

Patients with angina and nonobstructive coronary artery disease (CAD) experiencing both epicardial coronary spasm and high microvascular resistance face a worse prognosis. Rho-kinase activation may contribute to this condition, but fasudil treatment improved microvascular resistance.

Area of Science:

Cardiology
Vascular Biology
Clinical Medicine

Background:

Many patients with angina undergoing coronary angiography show no obstructive coronary artery disease (CAD).
Coronary functional abnormalities, affecting both epicardial and microvascular arteries, are implicated in these patients.
This study investigates the prognostic significance of these abnormalities.

Purpose of the Study:

To comprehensively assess the significance of coronary functional abnormalities in patients with angina and nonobstructive CAD.
To evaluate the combined role of epicardial coronary spasm and microvascular dysfunction.
To identify predictors of cardiac events in this patient cohort.

Main Methods:

Prospective enrollment of 187 patients with angina and nonobstructive CAD.
Acetylcholine provocation test for vasospastic angina (VSA) and index of microcirculatory resistance (IMR) measurement.
Follow-up for cardiac events and analysis of prognostic factors, including IMR and VSA.

Main Results:

Vasospastic angina (VSA) was identified in 68% of patients.
Increased IMR was a significant predictor of cardiac events (HR 1.05, p=0.002).
Patients with both high IMR (≥18.0) and VSA had a significantly worse prognosis.

Conclusions:

The coexistence of epicardial coronary spasm and increased microvascular resistance in nonobstructive CAD is linked to adverse outcomes.
Rho-kinase activation is suggested to play a role in the pathophysiology.
Fasudil, a Rho-kinase inhibitor, effectively improved microvascular resistance in VSA patients.

Read full analysis

Abstract

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.

Keywords:

IMR Rho-kinase coronary spasm microvascular dysfunction nonobstructive coronary artery disease

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