Methods:

The authors performed a systematic review and meta-analysis for studies published in English between 1980 and January 2017, assessing the composite primary outcome of all-cause death and nonfatal myocardial infarction (MI) using random-effects models to estimate pooled incidences. Secondary outcomes were the single occurrence of all-cause death, nonfatal MI, and cardiovascular hospitalization defined as chronic heart failure, cardiac arrhythmias, acute coronary sydromes, or any other manifestation of ischemic heart disease. Search terms included “syndrome X” and “microvascular angina.” Planned subgroup analyses were according to: (i) definition of “normal” coronary arteries (less than obstructive coronary artery disease [CAD], i.e., <50% coronary stenosis vs. absence of any angiographically appreciable atherosclerosis); (ii) presence or absence of documentation of myocardial ischemia including documented coronary dysfunction) as a prerequisite inclusion criterion in the various studies; (iii) the clinical presentation: typical angina, vasospastic angina, and “undefined” angina type, including patients with atypical angina or angina equivalents, and (iv) the diagnostic modality to assess CAD, either invasive coronary arteriography (ICA) or coronary computed tomography angiography (CCTA). Exclusion criteria: studies including acute coronary syndrome, and stress and other cardiomyopathies.