Whole heart atherosclerosis volume and risk for major adverse cardiovascular events across the clinical likelihood for obstructive CAD; the CONFIRM2 study

Introduction: The totality of atherosclerosis from the coronary tree can be measured with quantitative coronary CT and is increasingly being recognized as important marker for future cardiovascular events. We evaluated the risk and absolute event rates of plaque volume staging systems and provided analyses according to the clinical likelihood of obstructive CAD. Methods: CONFIRM2 is an ongoing, global, multicenter, observational registry that included patients with clinically indicated coronary CT angiography and follow-up for major adverse cardiovascular events (MACE). Patients without cardiac symptoms and prior CAD were excluded. Atherosclerosis was quantified across all coronary segments by AI-QCT. Total plaque volume (TPV) was categorized into non-calcified plaque (NCPV, HU <350) and calcified (HU>350). The primary end point was the incidence rate of MACE over at 4 years and included all-cause mortality, myocardial infarction, stroke, congestive heart failure, late revascularizations (occurring >90 days post index CCTA), and hospitalization for unstable angina. Secondary endpoint included Death, MI, and stroke. The prognostic value of TPV and NCPV was evaluated across the pretest likelihood according to the ESC Risk Factor Weighted Likelihood (ESC RF-CL). Results: A total of 6061 patients (mean age 58.6 ± 12.1 years, 48.6% male) were included and the mean follow-up duration was: 4.4 ± 1.8 years. According to the ESC RF-CL for obstructive CAD, patients were classified as very-low, low, and moderate risk in 36.0%, 43.0%, and 22.0%, and obstructive CAD rates were 6.8%, 15.7%. and 28.2, respectively. Within the total cohort, TPV >0–250, 250–750, and >750 mm³ were associated with MACE: HR 2.5 (95% CI 1.1, 5.6), HR 10.1 (95% CI 4.4, 22.9), and HR 15.9 (95% CI 6.7, 38.0) compared with TPV=0. According to RF-CL very-low, low, and moderate, the MACE rates were: 0.7, 2.9, 0.0% for TPV=0 mm³; 2.3%, 3.6%, 4.6% for TPV >0–250 mm³; 10.3%, 12.3%, 13.5% for TPV 250–750 mm³; and 18.8%, 16.7%, and 19.8% for TPV>750 mm³. Findings were consistent for the secondary endpoint. Conclusion: Among a large cohort of symptomatic patients evaluated by coronary CT angiography, the burden of atherosclerosis by AI-QCT was the main driver for cardiovascular events. Absolute event rates were consistently higher by each plaque volume stage, and consistent across the clinical likelihood subgroups for obstructive CAD. While quantitative atherosclerosis was present in the majority of patients, risk increased significantly from 250 mm³ of TPV during intermediate term follow-up.