IMPACT OF STRESS CARDIAC COMPUTED TOMOGRAPHY MYOCARDIAL PERFUSION ON DOWNSTREAM RESOURCES AND PROGNOSIS IN PATIENTS WITH SUSPECTED OR KNOWN CORONARY ARTERY DISEASE: A MULTICENTRE INTERNATIONAL STUDY - THE CTP-PRO STUDY

Background: Stress computed tomography perfusion (Stress-CTP) is a CT-based functional technique that can be added to coronary computed tomography angiography (cCTA) to improve management of patients with suspected coronary artery disease (CAD). The aim of the study is to evaluate the usefulness of combined evaluation of coronary anatomy and myocardial perfusion in intermediate to high-risk patients for suspected CAD or with known disease in terms of clinical decision-making, resource utilization and outcomes. The purpose of the substudy on circulating biomarkers is to identify, in the population of patients evaluated with CCTA, transcriptional biomarkers in peripheral blood of different CAD subtypes, with the aim of refining clinical decision making. Methods: CTP-PRO study is a cooperative, international, multicentre, prospective, randomized controlled study evaluating the cost-effectiveness of a CCTA+CTP strategy (Group A) versus usual care (Group B) in intermediate-high risk patients with suspected or known CAD who undergo clinically indicated diagnostic evaluation. Data regarding downstream testing, hospitalizations, revascularizations, major adverse cardiac events (MACE) as unstable angina, non-fatal myocardial infarction and cardiovascular death after index test were collected at 1-year follow-up and 2-year follow-up. Patients randomized to Group A at Centro Cardiologico Monzino received blood sampling for peripheral blood gene expression assessment. Results: At June 15th 2023, 805 consecutive patients were prospectively enrolled at 9 sites and uploaded in eCRF, of which 453 (56%) had previous revascularization. 413 patients were randomized to Group A, 246 of them with obstructive CAD and 143 of them, according to CTP performance, with inducible ischaemia. Remaining 392 patients were randomized to Group B (278 to Stress CMR, 56 to Exercise Echocardiography, 17 to Exercise ECG and 41 to SPECT), 90 of whom with inducible ischaemia according to test results. At 1-year follow-up, no significant differences were found between two groups in terms of downstream non-invasive testing (p: 0.382), while more hospitalizations, invasive assessment (both p: 0.021) and revascularization (p: 0.003) were recorded in patients randomized to Group A. No significant differences were found between two groups in terms of MACEs. At 2-year follow-up, no significant differences were found between two groups in terms of downstream non-invasive and invasive testing, hospitalization, revascularization and MACEs. At whole-blood transcriptome analysis, highly significant differences in the circulating transcriptome were found between patients with non-obstructive CAD compared to those with obstructive CAD at cCTA, and in the subset of patients with obstructive CAD, between those with and without inducible ischaemia at Stress-CTP. Conclusions: CT-based management of high-risk patients for CAD is associated with comparable rate of downstream non-invasive testing compared to standard of care. Good prognosis is warranted if clinical decision-making is based on combined anatomical and functional information. Whole-blood transcriptome is able not only to accurately discriminate between subjects with and without obstructive CAD at cCTA, but also to identify subjects with obstructive CAD and inducible ischaemia at Stress-CTP.