Endothelial Dysfunction in Myocardial Infarction With Non-Obstructive Coronary Arteries and Ischemia With Non-Obstructive Coronary Arteries: Mechanisms and Clinical Approach

Myocardial infarction with non-obstructive coronary arteries (MINOCA) and ischaemia with non-obstructive coronary artery disease (INOCA) are increasingly recognised syndromes in which endothelial dysfunction forms the mechanistic bridge between vascular biology and clinical ischaemia. In health, the endothelium preserves vascular homeostasis by regulating tone, platelet activity, and inflammation; when this regulation fails, vessels assume a pro-constrictive, pro-thrombotic, and pro-inflammatory state capable of causing epicardial vasospasm, microvascular dysfunction, or plaque erosion—provoking genuine infarction and arrhythmias despite unobstructed arteries. This paper follows the continuum from these mechanisms to their clinical expression. It traces the evolution from early angiographic observations to contemporary imaging such as CMR, IVUS, and OCT, and outlines a chronological diagnostic pathway from the emergency department to the catheterisation laboratory. Subtle but actionable clues are highlighted across the clinical history, ECG, echocardiography, and angiography, demonstrating that a positive, mechanism-based diagnosis of endothelial dysfunction is feasible even when invasive testing is unavailable. Management is directed by the dominant mechanism calcium-channel blockers and nitrates for vasospastic angina; β-blockers or metabolic agents for microvascular angina supported by endothelial stabilisers, cardiac rehabilitation, and psychosocial care. Persistent endothelial dysfunction is associated with later heart-failure development, particularly HFpEF, emphasising the need for early recognition and tailored therapy. The chapter concludes with real-world challenges and emerging perspectives, including standardised testing, AI-assisted imaging, and precision therapeutics. Ultimately, understanding endothelial dysfunction links mechanisms to clinical practice, reframing MINOCA and INOCA as diagnosable and treatable syndromes that demand mechanism-based, preventive care.