Patients sometimes present with classic exertional chest pain, abnormal stress testing, or even troponin-positive events, and then return from coronary angiography with the news that the large epicardial arteries are clean. The reflexive interpretation that the symptoms must therefore be non-cardiac is wrong roughly half the time. A substantial fraction of these presentations represent ischemia with no obstructive coronary arteries — INOCA — driven by dysfunction of the coronary microcirculation, the network of arterioles and capillaries that a standard angiogram cannot visualize. Mehta and colleagues, in a comprehensive review of INOCA, emphasized that the syndrome carries genuine prognostic weight, with increased rates of major adverse cardiac events compared to truly asymptomatic populations, and disproportionately affects women.
The pathophysiology is endothelial. Bairey Merz and colleagues described two principal mechanisms: impaired endothelium-dependent vasodilation, in which the small vessels fail to relax in response to flow-mediated nitric oxide release; and microvascular spasm, in which segments of the small vessels constrict inappropriately under sympathetic or acetylcholine challenge. Both reduce myocardial blood flow at the level of supply, especially during the increased demand of exertion, even when the upstream epicardial arteries remain widely patent. Smilowitz, Toleva, Chieffo, Perera, and Berry’s contemporary clinical review consolidated diagnostic approaches including coronary flow reserve measurement, intracoronary acetylcholine testing, and cardiac magnetic resonance perfusion imaging, all of which can demonstrate microvascular dysfunction that catheter-based angiography misses.
Recognition matters because treatment differs. Standard antianginal therapy still helps, but the most effective regimens combine endothelium-supporting medications — long-acting nitrates, calcium channel blockers, ranolazine, and in selected patients ACE inhibitors or statins — with intensive risk-factor management of hypertension, dyslipidemia, dysglycemia, and smoking, plus structured exercise training, weight optimization, and stress reduction. Patients should be told explicitly that their pain is real, that the standard catheterization findings do not exclude coronary disease, and that the lifestyle and pharmacologic levers in microvascular disease are well-defined and effective. The arteries that look clean on film are not always behaving cleanly under demand, and the medical system is gradually catching up to a disease that has been underdiagnosed for decades.
References:
- Mehta, P. K., Huang, J., Levit, R. D., Malas, W., Waheed, N., & Bairey Merz, C. N. (2022). Ischemia and no obstructive coronary arteries (INOCA): A narrative review. Atherosclerosis, 363, 8-21.
- Bairey Merz, C. N., Pepine, C. J., Shimokawa, H., & Berry, C. (2020). Treatment of coronary microvascular dysfunction. Cardiovascular Research, 116(4), 856-870.
- Smilowitz, N. R., Toleva, O., Chieffo, A., Perera, D., & Berry, C. (2023). Coronary microvascular disease in contemporary clinical practice. Circulation: Cardiovascular Interventions, 16(6), e012568.
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