Coronary artery spasm and impaired myocardial perfusion in patients with ANOCA: Predictors from a multimodality study using stress CMR and acetylcholine testing

Highlights

• Assessment of vasomotor dysfunction by CMR and acetylcholine testing is feasible.

• Coronary artery spasm and impaired microvascular vasodilation coexist.

• Age and previous myocardial infarction are independent predictors of low MPRI.

• Epicardial spasm is associated with low MPRI.

• Prior PCI is predictive for epicardial spasm and female sex for microvascular spasm.

Abstract

Background

Functional coronary disorders such as coronary spasm and microvascular dysfunction (including microvascular spasm and impaired microvascular dilatation) are frequent findings among patients with angina and non-obstructed coronary arteries (ANOCA). In this study, we investigated a potential association of coronary spasm and myocardial perfusion abnormalities as well as predictors of such functional coronary disorders in ANOCA patients using a multimodality diagnostic strategy including adenosine stress CMR and intracoronary acetylcholine testing.

Methods

We enrolled 129 patients with ANOCA who underwent acetylcholine testing and adenosine stress perfusion CMR. Patients were allocated to 3 groups according to their spasm testing result with regard to standardized COVADIS criteria: 1) epicardial spasm, 2) microvascular spasm, and 3) no spasm. The myocardial perfusion reserve index (MPRI) was semiquantitatively determined from adenosine stress perfusion CMR. Multivariate regression analyses were performed to identify predictors of coronary functional disorders.

Results

Patients with epicardial spasm had lower MPRI than patients without, whereas MPRI was preserved in patients with microvascular spasm. Multivariate analyses revealed age, previous myocardial infarction, LVEF and epicardial spasm as independent predictors of diminished MPRI, whereas previous PCI was associated with epicardial spasm, and female sex was a strong predictor of microvascular spasm.

Conclusions

Our results demonstrate coexistence of different functional coronary disorder endotypes involving the macro- and microvascular level of the coronary circulation in patients with ANOCA. We demonstrate that epicardial spasm is associated with diminished myocardial perfusion reserve and report further predictors of coronary functional disorders.

Introduction

About 50% of patients undergoing coronary angiography due to suspected ischemic heart disease are found to have angina and unobstructed coronary arteries (ANOCA) [1]. Nevertheless, this common clinical scenario still represents a diagnostic challenge. Functional coronary artery disorders such as coronary artery spasm or impaired myocardial perfusion reserve affecting the epicardial or microvascular component of the coronary tree are frequently found among these patients [[2], [3], [4]]. Thus, comprehensive assessment of epicardial and microvascular coronary function is recommended and can be performed invasively by an interventional diagnostic procedure (IDP) [4,5]. However, in the forthcoming era of ischaemia-driven percutaneous intervention (PCI), most stable patients are supposed to undergo non-invasive ischaemia imaging as a gate-keeper before entering the catheter laboratory. As a consequence in the real-world setting, it is likely that only a minority of patients with a negative non-invasive test will undergo subsequent invasive coronary angiography in order to assess coronary function. (Semi-)Quantitative myocardial perfusion analysis of cardiac magnetic resonance (CMR) imaging or positron-emission-tomography (PET) allows the assessment of myocardial perfusion at rest and during pharmacological hyperaemia as surrogates for coronary microvascular vasodilator function. Reliable coronary spasm testing, however, relies on intracoronary pharmacological provocation, e.g. using acetylcholine, and several recent studies have demonstrated that coronary artery spasm is the most prevalent mechanism of angina in patients with ANOCA [[4], [5], [6]].

Data on intracoronary acetylcholine spasm provocation following non-invasive ischaemia assessment using adenosine stress perfusion CMR are scarce. Thus, little is known about the association of coronary spasm endotypes (epicardial and microvascular spasm) and abnormalities of microvascular dilatation. The aim of the present study was to investigate the association and identify predictors of diminished myocardial perfusion reserve and coronary spasm endotypes in patients with ANOCA using adenosine stress perfusion CMR imaging and intracoronary acetylcholine spasm provocation testing.