Coronary artery disease (CAD) remains one of the leading causes of morbidity and mortality worldwide, contributing significantly to cardiovascular events like myocardial infarction (MI) and sudden cardiac death [1].

The pathophysiology of CAD involves a complex interplay of biological, systemic, and hemodynamic factors [2], as confirmed by recent studies [[3], [4], [5]]. In particular, endothelial shear stress (ESS) has gained momentum [6], propelled by advances in computer simulation technologies [7]. ESS, the friction tension exerted by blood flow on the arterial endothelium, plays a crucial role in maintaining vascular homeostasis and in the development of atherosclerosis [2]. Abnormal ESS patterns have been linked to the initiation and progression of coronary atherosclerotic lesions [3,8], suggesting a connection between distinct ESS features and adverse plaque characteristics, such as increased plaque burden, necrotic core expansion, and fibrous cap thinning. [4,9,10]. Moreover, ESS has emerged as a strong predictor of atherosclerotic plaque destabilization and rupture [[11], [12], [13]], and, consequently, adverse cardiovascular outcomes [[12], [13], [14], [15], [16]].

The Functional Assessment in Elderly MI Patients with Multivessel Disease (FIRE) trial was a \guided complete revascularization versus a culprit-only strategy in older patients with MI in the context of a multivessel CAD. The trial demonstrated that a complete revascularization strategy guided by physiological assessment was associated with a lower risk of adverse cardiovascular events at one-year follow-up [17].

Aligning with emerging evidence supporting the assessment of coronary physiology in older MI patients with MVD, this sub-analysis of the FIRE trial tested two key hypotheses: (i) incorporating advanced hemodynamic and anatomical analysis into this assessment could improve the identification of patients at higher risk of complications, and (ii) that distinct ESS patterns derived from personalized computational fluid dynamics (CFD) simulations in non-culprit, no-flow limiting coronary lesions have a significant causal link to CAD outcomes in older patients. To test these hypotheses, interventional cardiologists have conducted CFD simulations using a validated framework, with computational costs compatible with clinical practice [3,[18], [19], [20]].