Enhanced coronary physiology assessment with endothelial shear stress predicts residual cardiovascular risk in older patients with myocardial infarction

Background: The relationship between traditional risk factors, translesional hemodynamics, and plaque vulnerability remains incompletely understood. Endothelial shear stress (ESS) has recently emerged among the key players determining lesions instability and cardiovascular risk. Aims: We aimed to evaluate the prognostic value of ESS-based quantities and their interplay with anatomical and clinical factors in predicting adverse cardiovascular events in older patients with multivessel coronary artery disease (MVD). Methods: This post hoc analysis of the Functional Assessment in Elderly MI Patients with Multivessel Disease (FIRE) trial included older patients (≥75 years) with acute myocardial infarction (MI) and MVD undergoing percutaneous coronary intervention (PCI). ESS was assessed by angiography-based computational fluid dynamics simulations and the topological shear variation index (TSVI), recently emerged as predictor of future MI measurable within a clinical framework, was computed in non-culprit coronary lesions with negative functional assessment left untreated. The primary endpoint was major adverse cardiovascular events (MACE) at one year, defined as a composite of all-cause death, non-fatal MI, stroke, and ischemia-driven revascularization. Multivariate Cox regression and causal inference analysis were used to assess the prognostic role of anatomo-functional metrics alongside traditional risk factors. Results: A total of 335 FIRE trial patients were analyzed. The median percentage area stenosis (%AS), lesion length, time-averaged ESS, and TSVI were 57.2 %, 12.3 mm, 2.9 Pa, and 59.2 m-1, respectively. Severe lesions were associated with a higher risk of the primary outcome (hazard ratio, HR, 1.024, 95 % confidence interval, CI, 1.002–1.046, p = 0.031). Longer lesions were significantly linked to an increased risk of all-cause death (HR 1.042, 95 % CI 1.009–1.077, p = 0.013), while TSVI was associated with higher risk of MI (HR 1.006, 95 % CI 1.000–1.012, p = 0.014) and ischemia-driven revascularization (HR 1.006, 95 % CI 1.000–1.012, p = 0.021). The inclusion of %AS, lesion length, and TSVI significantly improved multivariate outcome prediction. Causal inference analysis indicated that TSVI had a strong causal association with both MI and revascularization, with an information content at least equal to that of %AS. Conclusions: TSVI, rather than absolute ESS magnitude, plays a key role in predicting acute events in older MI patients with MVD. Integrating ESS-based factors with traditional clinical and anatomical factors significantly enhances risk prediction and helps refine management strategies for this challenging patient population.