Microvascular angina and the continuing dilemma of chest pain with normal coronary angiograms

Abstract

Since initial reports over 4 decades ago, cases of patients with angina-like chest pain whose coronary angiograms show no evidence of obstructive coronary artery disease and who have no structural heart disease continue to be a common occurrence for cardiologists. Many features of this patient population have remained constant with successive reports over time: a female predominance, onset of symptoms commonly between 40 and 50 years of age, pain that is severe and disabling, and inconsistent responses to conventional anti-ischemic therapy. Because patients may have had abnormal noninvasive testing that led to performance of coronary angiography, investigators have sought to show an association of this syndrome with myocardial ischemia. Abnormalities in coronary flow and metabolic responses to stress have been reported by several groups, findings consistent with a microvascular etiology for ischemia and symptoms, but others have questioned the presence of ischemia, even in patients selected for abnormal noninvasive testing. Despite considerable efforts by many groups over 4 decades, the syndrome remains controversial with regard to pathophysiology, diagnosis, and management.

Figures

1. Contribution of Nitric Oxide to Epicardial and Microvascular Coronary Tone

The effect of risk factors for coronary atherosclerosis on the change in resting coronary vascular tone with L-NMMA, an antagonist of NO synthesis. The percent change in the coronary vascular resistance, flow, and proximal and distal epicardial diameters with L-NMMA are compared in patients with ≥ 1 risk factor (open circles) and in patients without risk factors (solid circles). Results expressed as mean ± SEM. † P<0.001, and denotes differences in the response to L-NMMA by repeat-measures analysis of variance between patients with and patients without risk factors. *P<0.05, and **P,0.01 denote differences between rest and post-LNMMA measurements in each group. (From reference , with permission)

2. Atherosclerosis Risk Factors and Coronary Tone During Endothelial Stimulation

The impact of risk factors for coronary atherosclerosis on the vascular effects of acetylcholine before and after inhibition of nitric oxide synthesis with L-NMMA.. The percent change in the coronary vascular resistance, flow, and proximal and distal epicardial diameters with acetylcholine are compared in patients with ≥ 1 risk factor (open circles) and in patients without risk factors (solid circles) for atherosclerosis. Responses to the peak dose of acetylcholine are compared before and after L-NMMA in the two groups. Results expressed as mean ± SEM. †P<0.03, and denotes differences in the response to acetylcholine between patients with and patients without risk factors. *P<0.05, and **P,0.01 denote differences between control and post-LNMMA measurements in each group. (From reference , with permission)

3. Left Ventricular Functional Responses to Stress

Comparison of the quantitative myocardial response to the infusion of incremental doses of dobutamine in healthy control subjects (open circles) and in patients with chest pain and normal coronary angiograms (solid circles). Results expressed as mean ±S EM. P value corresponds to comparison of the different responses by repeat-measures analysis of variance. (From reference , with permission)

4. Chest Pain During Cardiac Catheterization: The Sensitive Heart

Prevalence of typical chest pain experienced during cardiac catheterization in 36 patients with chest pain and normal coronary angiograms (CPNCA), 44 patients with coronary artery disease (CAD) and 10 patients with valvular heart disease (VHD) provoked by pacing from apex of right ventricle at 5 beats over resting heart rate and/or injection of contrast media into the left coronary artery. (Adapted from reference , with permission)

5. Connecting the Dots.....

Future research should establish a coherent pathophysiology that links coronary microvascular dysfunction with myocardial ischemia. For the diagnosis to be clinically relevant, testing that separates those patients whose symptoms are due to myocardial ischemia from those whose pain is non-ischemic should be validated by multiple groups, and strategies for effective management must be supported by randomized clinical trials.