Sixth late-breaking presentation from CONFIRM2 Registry demonstrates 12-fold risk gradient based on total plaque burden
December 15, 2025 (DENVER, CO) – Cleerly, a leader in AI-based cardiovascular imaging, presented new, late-breaking science from the international CONFIRM2 Registry at the Global CVCT Scientific Program 2025 in Washington, DC.
The study, "AI-Guided Quantification of Atherosclerosis on Coronary CT for Identification of High-Risk Individuals in Non-Obstructive CAD: International, Multi-Center Study," analyzed 6,550 patients (51.4% female, mean age 59) over 4.4 years who underwent coronary computed tomography angiography (CCTA) with AI-based quantitative coronary CT analysis (AI-QCT) across international sites.
The findings indicated:
- Patients with non-obstructive CAD and high plaque burden (>750mm³) experienced a 21.9% MACE rate, exceeding the 19.5% rate seen in obstructive CAD patients with similar plaque volumes, demonstrating that total plaque burden drives risk independent of stenosis severity.
- AI-QCT plaque quantification identifies a 12-fold risk gradient in non-obstructive disease: MACE rates increased from 1.7% with no measurable plaque to 21.9% with high plaque burden (>750mm³), revealing previously unrecognized risk stratification in patients traditionally considered lower risk.
- Event rates challenge traditional risk assessment: While overall MACE rates differed between non-obstructive (3.3%) and obstructive CAD (14%), patients with non-obstructive disease and substantial plaque burden showed event rates approaching or exceeding those with flow-limiting stenoses, 18.4% vs 17% for Obstructive vs Non-Obstructive at TPV > 750 mm3.
- After adjusting for baseline risk factors, MACE rates for patients with non-obstructive disease but high total and non-calcified plaque volumes were similar to those with obstructive disease and lower plaque volumes. This signifies a sufficient burden of plaque in non-obstructive disease may result in a critical mass of vulnerable disease that would warrant earlier intervention.
"These findings fundamentally change how we should assess cardiac risk in patients by addressing the historically overlooked risk of non-obstructive coronary artery disease," said Andrew D. Choi, MD, FACC, MSCCT, Director of Noninvasive Cardiology at The George Washington University School of Medicine. "By quantifying total plaque burden throughout the coronary tree, we've identified specific thresholds of patients with mild narrowing, but significant non-obstructive CAD that can carry equivalent or even potentially greater risk than those with traditionally identified severe narrowing. These findings reinforce the clinical value of whole heart plaque analysis in guiding clinical trials, enhancing preventive care decisions, and improving outcomes for the substantial population of patients with non-obstructive coronary disease.”
The study addresses evidence gaps by demonstrating how Cleerly’s AI-QCT enables comprehensive plaque quantification that supports clinical risk stratification beyond traditional assessment. The identification of a "critical mass" threshold where non-obstructive plaque burden drives MACE risk comparable to obstructive disease supports expanding cardiovascular risk assessment to include total atherosclerotic burden.
This marks the sixth late-breaking clinical science presentation from the CONFIRM2 Registry, which continues to provide groundbreaking insights into how AI-QCT transforms cardiovascular risk assessment.
About Cleerly
Cleerly is the company on a mission to eliminate heart attacks by creating a new standard of care for heart disease. Through its FDA-cleared solutions driven by artificial intelligence, Cleerly supports comprehensive phenotyping of coronary artery disease, as determined from advanced noninvasive CT imaging. Cleerly’s approach is grounded in science, based on millions of images from over 40,000 patients. Led by a world-class clinical and technical team, Cleerly enhances health literacy for each and every stakeholder in the coronary care pathway. For more information, please visit: cleerlyhealth.com.
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Cleerly : October 27, 2025
