BACKGROUND: Coronary plaque features are imaging biomarkers of cardiovascular risk, but less is known about sex-specific patterns in their prognostic value. This study aimed to define sex differences in the coronary atherosclerotic phenotypes assessed by artificial intelligence–based quantitative computed tomography (AI-QCT) and the associated risk of major adverse cardiovascular events (MACEs). METHODS: Global multicenter registry including symptomatic patients with suspicion of coronary artery disease referred for coronary computed tomography angiography. AI-QCT analyzed 16 coronary artery disease features. The primary end point was MACE defined as death, myocardial infarction, late revascularization, cerebrovascular events, unstable angina, and congestive heart failure. RESULTS: Among 3551 patients (mean age, 59±12 years; 49.5% women), MACE occurred in 3.2% of women and 6.1% of men during an average follow-up of 4.8±2.2 years. The AI-QCT features total plaque volume, noncalcified plaque, calcified plaque, and percentage atheroma volume were significantly higher in men ( P <0.001), and high-risk plaques were more prevalent (9.2% versus 2.5%; P <0.0001). Independent of age and cardiovascular risk factors, the AI-QCT-derived features of total plaque volume, noncalcified plaque, calcified plaque, and percentage atheroma volume conferred a higher relative risk of MACE in women than men. For every 50-mm ³ increase in total plaque volume, relative risk increased by 17.7% (95% CI, 1.12–1.24) in women versus 5.3% (95% CI, 1.03–1.07) in men ( P _interaction <0.001); for noncalcified plaque, relative risk increased by 27.1% (95% CI, 1.17–1.38) versus 11.6% (95% CI, 1.08–1.15; P _interaction =0.0015); and for calcified plaque, relative risk increased by 22.9% (95% CI, 1.14–1.33) versus 5.4% (95% CI, 1.01–1.10; P _interaction =0.0012), respectively. Similarly, for percentage atheroma volume, the risk was higher in women. The findings remained unchanged when restricted to a secondary composite end point (death and myocardial infarction). CONCLUSIONS: The AI-QCT plaque features, total plaque volume, noncalcified plaque, calcified plaque, and percentage atheroma volume, conferred a higher relative MACE risk in women and may prompt more aggressive antiatherosclerotic therapy and reinforced preventive interventions. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04279496.

Purpose: Cardiac rehabilitation (CR) has been proven to reduce mortality and morbidity in patients with cardiovascular disease. Machine learning (ML) techniques are increasingly used to predict healthcare outcomes in various fields of medicine including CR. This systemic review aims to perform critical appraisal of existing ML-based prognosis predictive model within CR and identify key research gaps in this area. Review Methods: A systematic literature search was conducted in Scopus, PubMed, Web of Science, and Google Scholar from the inception of each database to January 28, 2024. The data extracted included clinical features, predicted outcomes, model development, and validation as well as model performance metrics. Included studies underwent quality assessments using the IJMEDI and Prediction Model Risk of Bias Assessment Tool checklist. Summary: A total of 22 ML-based clinical models from 7 studies across multiple phases of CR were included. Most models were developed using smaller patient cohorts from 41 to 227, with one exception involving 2280 patients. The prediction objectives ranged from patient intention to initiate CR to graduate from outpatient CR along with interval physiological and psychological progression in CR. The best-performing ML models reported area under the receiver operating characteristics curve between 0.82 and 0.91, with sensitivity from 0.77 to 0.95, indicating good prediction capabilities. However, none of them underwent calibration or external validation. Most studies raised concerns about bias. Readiness of these models for implementation into practice is questionable. External validation of existing models and development of new models with robust methodology based on larger populations and targeting diverse clinical outcomes in CR are needed. KEY PERSPECTIVE: What is novel? This systematic review is the first to critically appraise existing machine learning (ML)-based clinical prognostic models in cardiac rehabilitation (CR). It identifies key research gaps in ML application in CR and provides constructive suggestions for improving the quality of ML models specifically in CR. What are the clinical and/or research implications? The review demonstrates various clinical challenges in the CR setting that ML models have been used to address and their corresponding outcomes. It reveals potential limitations in existing models and offers recommendations to enhance the readiness of current and future models for implementation in clinical settings as clinical decision-support tools.