Long-term Prognostic Value of Sequential Coronary CT Angiography and Quantitative PET in Suspected Chronic Coronary Syndromes: A Multicentre study

Abstract

Abstract Background and Aims The long-term prognostic value of a guideline-recommended selective sequential anatomical-functional imaging strategy using coronary computed tomography angiography (CCTA) followed by quantitative [15O]H2O positron emission tomography (PET) remains uncertain. We evaluated its long-term prognostic value in patients with first symptoms suggestive of obstructive coronary artery disease (CAD). Methods In this multicentre European cohort, symptomatic patients first underwent CCTA and were selectively referred to quantitative [15O]H2O PET in case of suspected obstructive stenosis (≥50%). Patients were stratified according to CCTA findings and PET-derived ischaemia (normal CCTA; non-obstructive CAD on CCTA; obstructive CAD on CCTA without ischaemia; obstructive CAD on CCTA with ischaemia). The primary endpoint was a composite of all-cause mortality, non-fatal myocardial infarction (MI), and hospitalization for unstable angina (UA). Adjusted hazard ratios (aHRs) were calculated. Results Among 3,918 patients (61.0±9.8 years; 54.3% female) with a median follow-up of 5.1 [3.8-8.0] years, 278 (7.1%) experienced the primary endpoint. aHRs increased stepwise across CCTA-PET categories. Compared to normal CCTA, non-obstructive CAD and obstructive CAD without ischaemia were associated with a higher risk of the combined primary endpoint (aHR 1.89, [95%CI: 1.23-2.91], p=0.004; aHR 3.20, [95%CI: 1.95-5.25], p<0.001). Among patients with obstructive CAD on CCTA, PET-derived ischaemia further increased the risk of the primary endpoint (aHR 1.55, [95%CI: 1.05-2.30]; p=0.029), but not when excluding UA from the composite endpoint (aHR 1.37, [95%CI 0.90-2.07]; p=0.141). PET-derived ischaemia primarily predicted events within the first year, while obstructive CCTA findings remained associated with long-term hard outcomes. Conclusions A sequential strategy combining CCTA and quantitative [15O]H2O PET provides robust and incremental long-term risk stratification. While PET-derived ischaemia refines prediction of short-term and symptom-driven events, CCTA-derived CAD remains the principal determinant of long-term hard outcomes.