Abstract

The size of the heart may predict major cardiovascular events (MACE) in patients with stable chest pain. We aimed to evaluate the prognostic value of 3D whole heart volume (WHV) derived from non-contrast cardiac computed tomography (CT). Among participants randomized to the CT arm of the Prospective Multicenter Imaging Study for Evaluation of Chest Pain (PROMISE), we used deep learning to extract WHV, defined as the volume of the pericardial sac. We compared the WHV across categories of cardiovascular risk factors and coronary artery disease (CAD) characteristics and determined the association of WHV with MACE (all-cause death, myocardial infarction, unstable angina; median follow-up: 26 months). In the 3798 included patients (60.5 ± 8.2 years; 51.5% women), the WHV was 351.9 ± 57.6 cm3/m2. We found smaller WHV in no- or non-obstructive CAD, women, people with diabetes, sedentary lifestyle, and metabolic syndrome. Larger WHV was found in obstructive CAD, men, and increased atherosclerosis cardiovascular disease (ASCVD) risk score (p < 0.05). In a time-to-event analysis, small WHV was associated with over 4.4-fold risk of MACE (HR (per one standard deviation) = 0.221; 95% CI: 0.068-0.721; p = 0.012) independent of ASCVD risk score and CT-derived CAD characteristics. In patients with non-obstructive CAD, but not in those with no- or obstructive CAD, WHV increased the discriminatory capacity of ASCVD and CT-derived CAD characteristics significantly. Small WHV may represent a novel imaging marker of MACE in stable chest pain. In particular, WHV may improve risk stratification in patients with non-obstructive CAD, a cohort with an unmet need for better risk stratification. • Heart volume is easily assessable from non-contrast cardiac computed tomography. • Small heart volume may be an imaging marker of major adverse cardiac events independent and incremental to traditional cardiovascular risk factors and established CT measures of CAD. • Heart volume may improve cardiovascular risk stratification in patients with non-obstructive CAD.

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