What is the etiopathogenesis of coronary epicardial vasospasm in Coronary Artery Disease (CAD)?

Etiopathogenesis of Coronary Epicardial Vasospasm in CAD

Coronary epicardial vasospasm results from abnormal vasoconstriction of epicardial coronary arteries causing transient total or subtotal occlusion (>90% constriction), driven by endothelial dysfunction, smooth muscle hyperreactivity, and autonomic dysregulation, which can occur in both atherosclerotic and angiographically normal vessels. 1

Pathophysiological Mechanisms

Vascular Dysfunction

• Endothelial dysfunction is the primary driver, characterized by impaired nitric oxide (NO) production and enhanced vasoconstrictor responses 1, 2
• Smooth muscle hyperreactivity to vasoconstrictor stimuli (acetylcholine, serotonin, thromboxane A2) leads to inappropriate coronary constriction 3, 4
• The vasospasm can be focal or diffuse, affecting single or multiple epicardial vessels 1

Relationship to Atherosclerosis

• Vasospasm occurs in both atherosclerotic and non-atherosclerotic coronary arteries, representing a spectrum of disease 1
• When atherosclerosis coexists with vasospasm, patients experience worse prognosis compared to isolated vasospasm 1
• Endothelial impairment from atherosclerotic plaque predisposes to localized vasospastic responses at stenotic sites 1

Oxidative Stress and Inflammation

• Increased oxidative stress and inflammatory mediators contribute to microvascular injury and abnormal vasoreactivity 2
• Cardiometabolic risk factors (smoking, diabetes, hypertension, dyslipidemia) promote endothelial dysfunction through oxidative mechanisms 1, 5

Autonomic Dysregulation

• Cardiac autonomic dysfunction has been implicated in abnormal coronary vasoreactivity 2
• Enhanced alpha-adrenergic receptor sensitivity may contribute to inappropriate vasoconstriction 4

Clinical Context and Triggers

Provocative Factors

• Smoking is a major trigger for vasospasm 1, 4
• Cold stimulation, hyperventilation, cocaine use can precipitate episodes 1
• Electrolyte disturbances (potassium, magnesium deficiency) 1
• Autoimmune diseases and insulin resistance are associated conditions 1

Geographic and Demographic Variations

• Japanese and Taiwanese populations demonstrate markedly higher prevalence (24.3% and 19.3% multiple vessel spasm) compared to Caucasians (7.5%) 1
• This suggests genetic or environmental factors influence susceptibility to vasospasm 1

Overlap with Microvascular Dysfunction

Mixed Endotypes

• Epicardial vasospasm frequently coexists with coronary microvascular dysfunction (CMD), creating a mixed MVA/VSA phenotype 1
• Concomitant endothelial dysfunction is prevalent in most patients with inducible coronary spasm and impaired adenosine-mediated vasodilation 1
• This overlap is associated with worse prognosis than isolated epicardial spasm 1

Diagnostic Confirmation

Provocative Testing

• Intracoronary acetylcholine during angiography is the gold standard, demonstrating >90% diameter reduction with symptoms and ST-segment changes 1, 4
• Alternative agents include ergonovine or methylergonovine 1, 4
• Hyperventilation and cold pressor tests have limited sensitivity 1

Clinical Pitfalls

• Spontaneous spasm during angiography is rarely observed, necessitating provocative testing in suspected cases 1
• The diagnosis requires documentation of both anatomic spasm and ischemic changes (symptoms plus ECG changes) 1
• Vasospasm can occur at sites of non-obstructive atherosclerotic plaque visible on intravascular imaging, not just angiographically normal vessels 2

Prognostic Implications

Risk Stratification

• Prognosis depends heavily on extent of underlying atherosclerotic disease 1
• Patients with non-obstructive lesions have coronary death rates of approximately 0.5% per annum 1
• Those with spasm superimposed on stenotic lesions have significantly worse outcomes 1
• Vasospasm can precipitate acute coronary syndromes, arrhythmias, sudden cardiac death, and syncope 4