Coronary microvascular dysfunction, microvascular angina, and treatment strategies

Abstract

Angina without coronary artery disease (CAD) has substantial morbidity and is present in 10% to 30% of patients undergoing angiography. Coronary microvascular dysfunction (CMD) is present in 50% to 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 or myocardial perfusion reserve <2.5 by positron emission tomography, cardiac magnetic resonance imaging, dilution methods, or intracoronary Doppler in the absence of coronary artery stenosis ≥50% or structural heart disease. Only 8 papers met the strict inclusion criteria. The papers were heterogeneous, using different treatments, endpoints, and definitions of CMD. The 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 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 published data. 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.

Keywords: cardiac syndrome X; coronary flow reserve; coronary microvascular dysfunction; microvascular angina; myocardial perfusion reserve.

Figure 1

Etiologies of chest pain without obstructive CAD. This figure illustrates the varying pathophysiologic mechanisms of chest pain without obstructive CAD grouped into three broad categories: non-cardiac; cardiac ischemic; and cardiac non-ischemic. The contribution of multiple potential pathophysiologies to cardiac syndrome X is highlighted. Microvascular angina overlaps partially with cardiac syndrome X as shown, but has a narrower pathophysiologic basis which is cardiac ischemic in nature..

Figure 2

Study Design Flow Diagram The search strategy for our systematic review is detailed. From the 285,399 subjects identified in an initial keyword search, only 8 articles met strict inclusion criteria. The number of articles excluded and their reasons for exclusion are detailed.