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

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.