Clinical characteristics and prognosis of patients with microvascular angina: an international and prospective cohort study by the Coronary Vasomotor Disorders International Study (COVADIS) Group

Introduction

Angina pectoris has been considered to be mainly caused by atherosclerotic obstructive coronary artery disease (CAD). However, up to 50% of patients undergoing diagnostic coronary angiography for typical chest pain have angiographically normal coronary arteries or non-obstructive CAD. In such cases, coronary functional abnormalities are implicated, including epicardial coronary artery spasm and coronary microvascular dysfunction (CMD). The latter is typically defined as increased susceptibility to vasoconstrictor stimuli resulting in microvascular spasm and/or impaired dilatation of coronary microvessels, with resultant inadequate increase in blood flow in response to stress. Thus, CMD may be the underlying mechanism in a large proportion of angina patients.

The term microvascular angina (MVA), originally proposed by Cannon and Epstein in 1988, is used for angina/myocardial ischaemia attributable to CMD. Recently, several studies with either invasive or non-invasive techniques for assessment of coronary physiology have provided extensive data, improving what is known about CMD and microvascular ischaemia. In addition, as the COronary VAsomotor Disorders International Study (COVADIS) Group, we have proposed the diagnostic criteria of MVA. Briefly, the diagnosis of MVA is established based upon symptoms suggestive of myocardial ischaemia in the absence of obstructive CAD (<50% diameter reduction and/or fractional flow reserve >0.80) associated with objective evidence of myocardial ischaemia and impaired coronary microvascular function defined by the following four findings: reduced coronary flow reserve (CFR), microvascular spasm, increased microvascular resistance, and/or coronary ‘slow flow phenomenon’.

To date, clinical studies have mainly been the single centre. Given the lack of evidence from international multi-centre studies, the clinical characteristics, and prognosis of patients with MVA remain to be fully elucidated. Our first objective was to study the clinical characteristics and health outcomes of patients with MVA in a large, prospective, international registry. Our second objective was to assess for associations by sex and ethnicity. Thus, in the present study, we undertook a multinational, multi-centre, multi-ethnic, prospective, observational, and longitudinal cohort study.