Prognostic impact of high-risk plaque morphology and impaired physiology in untreated non-culprit coronary lesions: a systematic review and meta-analysis

Background: The management of angiographically intermediate coronary lesions (AICLs) remains challenging. Although current guidelines recommend physiological assessment to guide treatment decisions, residual atherothrombotic risk related to vulnerable plaque morphology may persist in deferred non-culprit lesions (NCLs). We performed a systematic review and meta-analysis to evaluate the prognostic impact of high-risk plaque morphology and impaired physiology in untreated NCLs. Methods: A systematic search of PubMed, Embase, and Web of Science identified 10 studies that included both morphological (optical coherence tomography [OCT], intravascular ultrasound [IVUS], or near infrared spectroscopy) and physiological (fractional flow reserve [FFR], instantaneous wave-free ratio, quantitative flow ratio [QFR], Murray fractal law-based QFR, optical flow reserve, OCT-FFR, or IVUS-FFR) assessment in the same untreated AICLs. Overall, 4757 patients with 7662 untreated NCLs were stratified into four groups: reference, morphology-positive, functional-positive, and morpho-functional-positive. The primary endpoint was target vessel failure (TVF), defined as a composite of cardiac death, target-vessel myocardial infarction, and target-vessel revascularization. Hazard ratios (HRs) were pooled using random-effects models. Results: Compared with the reference group, TVF risk was increased in morphology-positive lesions (HR 2.94, 95% confidence interval [CI] 2.22-3.90) and functional-positive lesions (HR 3.59, 95% CI 1.56-8.24). The highest risk was observed in the morpho-functional-positive group. Indirect comparison showed no significant difference between morphology-positive and functional-positive lesions. Conclusions: High-risk plaque morphology and impaired physiology were independently associated with adverse outcomes in untreated NCLs, while their coexistence identified lesions at highest risk. An integrated morpho-functional assessment may improve risk stratification in multivessel coronary artery disease.