Contribution of Coronary Physiology and Imaging to Clinical Decision-Making in Patients with Coronary Artery Disease

Coronary physiology and intravascular imaging play a central role in guiding clinical decision-making in patients with coronary artery disease (CAD), yet their applications continue to expand beyond traditional indications. This thesis explores how physiology- and imaging-based strategies can refine risk stratification, improve diagnostic yield, and optimize procedural planning across a broad spectrum of clinical scenarios. Chapter 1 presents a meta-analysis including 24,285 patients, evaluating cardiovascular outcomes following deferred versus performed coronary revascularization based on intracoronary physiology. Over 2.6 years follow-up, physiology-guided deferral was associated with lower rates of all-cause death, cardiovascular death, and unplanned revascularization compared with revascularization, while no significant differences were observed for myocardial infarction (MI) or major adverse cardiovascular events (MACE). These findings support a prognostic role of intracoronary pressure indices beyond revascularization decision-making. Chapter 2 reports a patient-level pooled analysis of the DEFINE-FLAIR and iFR-SWEDEHEART trials with 5-year follow-up. Among 4,511 patients, iFR-guided revascularisation was associated at 5 years of follow-up with a higher incidence of MACE and death compared with FFR, while rates of non-cardiovascular death, non-fatal MI and unplanned revascularisation were similar between groups. These differences were predominantly driven by patients undergoing revascularization. Subgroup analysis of the primary endpoint revealed no significant interactions across baseline characteristics, including vessel location. Chapter 3 evaluates a wire-free diagnostic strategy combining angiography-derived indices of epicardial and microvascular function with acetylcholine testing, enabling comprehensive assessment of obstructive and non-obstructive myocardial ischemia. In 262 patients with chronic coronary syndrome from the AID-ANGIO study, this approach doubled the diagnostic yield compared with coronary angiography alone and demonstrated substantial agreement with wire-based assessment, resulting in frequent changes in therapeutic management. Chapter 4 focuses on procedural optimization, describing the development and external validation of the optical coherence tomography (OCT)–Bifurcation score, based on pre-procedural OCT features (calcified plaque at the side branch, carina length ≥1 mm, and side branch orifice length <1.7 mm), to predict side branch compromise during provisional stenting. This OCT-based score accurately identified lesions at high risk of side branch compromise, enabling improved procedural planning. Collectively, this work demonstrates that expanding the use of coronary physiology and imaging enhances diagnostic precision, prognostic assessment, and interventional strategy in contemporary CAD management.