Coronary artery spasm, also referred to as vasospastic angina or Prinzmetal's angina, remains a significantly under-recognized contributor to transient myocardial ischemia.
Despite being a functional and reversible narrowing of the coronary artery due to smooth muscle hyperreactivity, its unpredictable presentation can obscure diagnosis.
In contrast to fixed atherosclerotic obstruction, the vasospastic component does not always manifest in standard exercise testing. This mechanism challenges conventional paradigms, particularly in patients presenting with resting angina, minimal risk factors, and non-obstructive findings on angiography.
Pathophysiological Insights into Smooth Muscle Reactivity
Recent investigations have revealed that endothelial dysfunction, oxidative stress, and autonomic dysregulation are central to the pathogenesis of coronary artery spasm. A 2024 study from the Journal of Clinical Cardiology identified a polymorphism in the Rho-kinase pathway, particularly the ROCK2 gene variant, which increases susceptibility by amplifying contractility in vascular smooth muscle.
Elevated activity in Rho-kinase also contributes to microvascular dysfunction, which may coexist with epicardial spasms. A cardiovascular researcher at Kyoto University, emphasizes that "targeting this signaling axis may offer therapeutic potential in patients refractory to nitrates and calcium channel blockers."
Clinical Presentation: Subtle Patterns with Serious Implications
Patients experiencing coronary artery spasm often report transient chest discomfort, typically at rest or during the early morning hours. Unlike stable angina, this pain may not be reproducible on exertion. Some cases also involve silent ischemia, detectable only through ambulatory ECG or advanced cardiac imaging.
Electrocardiographic findings may mimic ST-segment elevation myocardial infarction (STEMI), yet coronary angiography often shows minimal or no fixed stenosis. Without provocation testing such as intracoronary acetylcholine or ergonovine challenge—the diagnosis may be overlooked.
Diagnostic Strategy: Beyond the Standard Angiogram
Traditional diagnostic tools may fall short in detecting dynamic constriction. Modern approaches emphasize:
- Provocative testing under controlled conditions to elicit spasm
- High-resolution intravascular imaging, including OCT and IVUS, to assess vessel wall integrity and endothelial disruption
- Biomarker profiling for systemic inflammation and oxidative stress markers (e.g., hs-CRP, ADMA)
Treatment Considerations: Personalizing Therapy
Calcium channel blockers remain the cornerstone of treatment, acting as effective vasodilators to reduce arterial hyperreactivity. Long-acting nitrates may be added, although tolerance remains a concern. In cases with poor response, Rho-kinase inhibitors are under investigation, showing promise in early-phase clinical trials.
Beta-blockers, especially non-selective forms, may worsen vasospasm and should be prescribed with caution. Lifestyle modifications targeting autonomic balance such as stress reduction and sleep regulation also play a supportive role, particularly when psychosomatic triggers are suspected. For high-risk individuals, implantable cardiac monitors may be used to track arrhythmic episodes associated with silent ischemia or aborted sudden cardiac arrest.
Emerging Perspectives in Coronary Spasm Research
Genetic and molecular profiling is paving the way for a precision cardiology approach. Studies from the National Heart Institute Singapore (2025) have highlighted that Asian populations may carry higher prevalence of spasm-prone endotypes, necessitating ethnic-specific management protocols. Additionally, wearable technologies incorporating real-time ECG and autonomic metrics are being tested to predict vasospastic events in ambulatory settings.
Coronary artery spasm is a clinically elusive but potentially serious condition that requires a high index of suspicion and sophisticated diagnostic strategies. When left undetected, it may lead to ischemic injury, arrhythmia, or sudden cardiac death despite normal angiographic findings. Advances in vascular imaging, pharmacogenomics, and molecular cardiology are shifting the landscape toward more nuanced diagnosis and targeted interventions.
