Angina without coronary artery disease (CAD) has substantial morbidity and is present in 10–30% of patients undergoing angiography. Coronary microvascular dysfunction (CMD) is present in 50–65% of these patients. The optimal treatment of this cohort is undefined. We performed a systematic review to evaluate treatment strategies for objectively defined CMD in the absence of CAD. We included studies assessing therapy in human subjects with angina and coronary flow reserve (CFR) or myocardial perfusion reserve (MPR) <2.5 by positron emission tomography (PET), cardiac magnetic resonance imaging (CMR), dilution methods, or intracoronary Doppler in the absence of coronary artery stenosis ≥50% or structural heart disease. Only 8 articles met strict inclusion criteria. The articles were heterogeneous, using different treatments, end-points, and definitions of CMD. Small sample sizes severely limit the power of these studies, with an average of 11 patients per analysis. Studies evaluating, sildenafil, quinapril, estrogen, and transcutaneous electrical nerve stimulation (TENS) application demonstrated benefits in their respective endpoints. No benefit was found with L-arginine, doxazosin, pravastatin, and diltiazem. Our systematic review highlights that there is little data to support therapies for CMD. We assess the data meeting rigorous inclusion criteria and review the related but excluded literature. We additionally describe the next steps needed to address this research gap, including a standardized definition of CMD, routine assessment of CMD in studies of chest pain without obstructive CAD, and specific therapy assessment in the population with confirmed CMD.

Recent analyses have found that coronary microvascular dysfunction (CMD) portends a poor prognosis in patients with and without obstructive epicardial coronary artery disease (CAD). Chest pain in the absence of epicardial CAD is a common entity. Angina caused by CMD, microvascular angina (MVA), is often indistinguishable from that caused by obstructive epicardial CAD. The recent emergence of noninvasive techniques that can identify CMD, such as stress positron-emission tomography (PET) and cardiovascular magnetic resonance (CMR) myocardial perfusion imaging, allow improved identification of MVA. Using these tools, higher risk patients with MVA can be differentiated from those at lower risk in the heterogeneous population historically labeled as cardiac syndrome X. Likewise, MVA can be diagnosed in those with obstructive epicardial CAD who have persistent angina despite successful revascularization. There is little evidence to support current treatment strategies for MVA and current literature has not clearly defined CMD or whether therapy improves prognosis.

BackgroundNormal or near‐normal coronary arteries (NNCAs) or nonobstructive coronary artery disease (CAD) are found on invasive coronary angiography in ≈55% of patients. Some attribute this to frequent referral of low‐risk patients. We sought to identify the referral indications, pretest risk, key clinical characteristics, sex, and outcomes in patients with NNCAs and nonobstructive CAD versus obstructive CAD on nonemergent invasive coronary angiography.Methods and ResultsOver 24 months, 925 consecutive patients were classified as having NNCAs (≤20% stenosis), nonobstructive CAD (21–49% stenosis), or obstructive CAD (≥50% stenosis). Outcomes included cardiac death, nonfatal myocardial infarction, and late revasclarization. NNCAs were found in 285 patients (31.0%), nonobstructive CAD in 125 (13.5%), and obstructive CAD in 513 (55.5%). NNCAs or nonobstructive CAD was found in 40.5% with stress ischemia, 27.9% after a non‐ST‐elevation myocardial infarction, and in 55.5% with stable or unstable angina. More women than men (53.5% versus 37.2%; P<0.001) had NNCAs or nonobstructive CAD across all referral indications. Pretest risk was high and ICA appropriate in 75.5% and 99.2% of patients, respectively. Annual rates of cardiac death or nonfatal myocardial infarction were 1.0%, 1.1%, and 6.7%, respectively, for patients with NNCAs, nonobstructive CAD, and obstructive CAD (P<0.001). No sex differences in outcomes were observed with either NNCAs, nonobstructive CAD, or obstructive CAD (P=0.84).ConclusionsMany (44.5%) patients undergoing nonemergent invasive coronary angiography have NNCAs or nonobstructive CAD despite high pretest risk, including ischemia and troponin elevation. Although women had more NNCAs or nonobstructive CAD, there were no differences in event rates by sex. Patients with NNCAs and nonobstructive CAD had very low event rates.