Spontaneous coronary artery dissection as a threshold disorder of coronary wall integrity

Spontaneous coronary artery dissection (SCAD) is an increasingly recognized cause of non-atherosclerotic acute myocardial infarction, predominantly affecting young and middle-aged women and patients during pregnancy or the postpartum period. Although major progress has been made in clinical recognition, angiographic diagnosis, conservative management, and extracoronary vascular screening, the molecular basis of SCAD remains incompletely understood. Here, we develop a provisional, evidence-integrating framework that conceptualizes SCAD as a threshold disorder of coronary wall integrity rather than as a variant of plaque rupture or a purely intimal tear-driven event. The available evidence indicates that the final common pathological event is intramural hematoma formation and true-lumen compression, whereas the threshold for this event is shaped by inherited susceptibility, extracellular matrix architecture, vascular smooth muscle cell and fibroblast regulation, vascular tone, local hemostatic containment, systemic arteriopathy, and reproductive or stress-related hemodynamic load. We critically evaluate inside-out and outside-in models of SCAD initiation, common and rare genetic architecture, the ambiguous role of fibromuscular dysplasia, pregnancy-associated SCAD, antithrombotic controversies, and emerging strategies for mechanism-informed risk stratification. We also define what is established, what remains controversial, and what should not yet be translated into routine practice. Finally, we propose a research roadmap centered on multiomic prospective cohorts, coronary wall models, high-resolution imaging phenotypes, reproductive vascular biology, and pragmatic clinical trials. The resulting taxonomy is intended to organize current evidence, identify priorities for mechanistic validation, and potentially support precision diagnosis, individualized antithrombotic decisions, reproductive counseling, genetic testing, and prevention of recurrence.