Background:Coronary CT angiography (CCTA) enables early noninvasive detection of coronary atherosclerosis, but its use in younger adults is limited by low pretest probability. Coronary artery disease polygenic risk score (CAD-PRS) may help identify individuals with increased likelihood of coronary plaque. Methods:We conducted a retrospective cohort study of patients without prior coronary artery disease who underwent CCTA between 2004 and 2021 and were genotyped through the Mass General Brigham Biobank (n = 1991), with follow-up through 2024. CAD-PRS was analyzed continuously and by risk categories (high [top decile], intermediate, low [bottom decile]). Plaque was classified as absent (CAD-RADS 0), non-obstructive (CAD-RADS 1-2), or obstructive (CAD-RADS 3-5). Extensive plaque was defined as ≥3-vessel involvement. Relative risk regression evaluated associations with plaque stratified by age. Kaplan-Meier and Cox proportional hazards models evaluated associations with adverse cardiovascular outcomes. Results:Plaque was present in 65.6% of participants, extensive plaque in 32.2%, and obstructive disease in 24.6%. Compared with the low-PRS group, high CAD-PRS was associated with greater risk of any plaque (RR 1.68, 95% CI 1.48-1.92), extensive plaque (RR 2.62, 95% CI 1.94-3.54), and obstructive disease (RR 2.82, 95% CI 1.87-4.27) (all P < .001). Associations were strongest among younger individuals (PRS-age interaction P = .017). CAD-PRS improved discrimination beyond age, sex, and traditional risk factors (C-statistic 0.832 [95% CI, 0.814-0.851] vs 0.803 [0.782-0.823]). High CAD-PRS was independently associated with increased cardiovascular events (aHR 2.76, 95% CI 1.55-4.92, P < .001). Conclusions:High CAD-PRS was independently associated with greater presence, extent, and severity of CAD on CCTA. The impact of genetic risk was strongest in younger adults-a group for whom identifying early atherosclerotic plaque may have the greatest impact.

Aims:Left bundle branch block (LBBB) is associated with mechanical dyssynchrony, heterogeneous perfusion, and adverse left ventricular (LV) remodeling. However, not all patients with LBBB develop cardiomyopathy, and dyssynchrony can occur without conduction defects. The role of microvascular dysfunction remains uncertain. We aimed to assess how mechanical dyssynchrony and perfusion heterogeneity relate to LV remodeling and function in patients with and without LBBB. Methods and results:We retrospectively analyzed 233 patients with isolated LBBB and 932 matched controls who underwent PET myocardial perfusion imaging, assessing mechanical dyssynchrony (phase entropy), myocardial blood flow (MBF), coronary vascular resistance (CVR), myocardial flow reserve (MFR), septal-to-lateral MBF ratio (SLR) for perfusion heterogeneity, LV volumes, and ejection fraction (EF). Compared to controls, patients with LBBB had greater dyssynchrony (56% vs. 40%), larger LV volumes, and lower EF (54% vs. 67%) (all p<0.001), and had higher stress CVR (37 vs. 34 mmHg/mL·min-1·g-1), lower stress MBF (2.4 vs. 2.6 mL/min/g), reduced MFR (2.4 vs. 2.6), and lower SLR (0.95 vs. 1.00) (all p<0.05). Among patients with dyssynchrony, SLR<1.0 identified those with more adverse remodeling. In multivariable regression, phase entropy and SLR independently predicted LV volumes and EF, with adverse effects of SLR reduction amplified in LBBB (interaction p<0.01). In the Cox proportional hazards analysis, phase entropy (HR:1.02, p=0.01), MFR (HR:0.62, p<0.001), and LVEF (HR:0.97, p<0.001) were independently associated with mortality and heart failure hospitalization, whereas LBBB was not. Conclusions:Mechanical dyssynchrony and perfusion heterogeneity independently predict adverse LV remodeling, irrespective of LBBB. Integrated imaging enhances cardiomyopathy stratification.

BACKGROUND:Cardiovascular complications from coronavirus disease 2019 (COVID-19) contribute to its morbidity. COVID-19 has been associated with coronary microvascular dysfunction (CMD), yet the long-term relationship is not well understood. We aimed to assess changes in CMD status and myocardial flow reserve (MFR among patients with prior COVID-19 infection using serial cardiac PET/CT imaging. METHODS:single-center study of 35 patients who underwent clinically indicated PET/CT before and after COVID-19 infection. They were compared with 70 historical COVID-19-negative controls matched 2:1 for age and sex, and cardiovascular risk factors. MFR less than 2 was used to define CMD. The primary outcome was the change in global MFR (ΔMFR = follow-up-baseline). Linear and conditional logistic regression were used to account for matching dependencies. RESULTS:The median interval between PET/CT studies among COVID-19 patients was 2.8 years. Most patients had mild symptoms, and 94% were immunized. Baseline perfusion abnormalities were similar between groups (13% vs 29%, P = 0.05). There was no significant difference in global ΔMFR between COVID-19 and control groups (0.07 vs -0.10, P = 0.23). CMD status remained unchanged among most participants (83% in the COVID-19 group and 60% in controls). CONCLUSIONS:Despite prior evidence of an association between COVID-19 and CMD, there were no apparent longitudinal changes in MFR and CMD status in patients with recovered COVID-19 infection. These findings suggest that mild COVID-19 infection does not confer persistent coronary microvascular dysfunction detectable by PET/CT.

Therapeutic Area ASCVD/CVD Risk Assessment Background Coronary artery calcium (CAC) testing is increasingly used in preventive cardiology. When CAC reveals extreme calcifications, further evaluation may be useful. However, calcification limit the diagnostic yield in of coronary CT angiography (CCTA). Photon-counting CT (PCCT) has superior spatial resolution and fewer artifacts, potentially enhancing the diagnostic accuracy to exclude high risk anatomy. However, data on its clinical utility in asymptomatic individuals with extreme CAC scores is limited. Methods This retrospective study analyzed asymptomatic patients with no prior coronary artery disease (CAD) who underwent PCCT-based CCTA at a single academic center between February 2024 and February 2025 after being identified with an extreme CAC score (>1000 Agatston units). Imaging was performed using a dual-source PCCT scanner with ultra-high resolution (UHR) mode (0.2mm slice thickness). Results Nineteen patients (mean age: 64.5 ± 10.3 years; 32% women) were analysed. Standard modifiable cardiovascular risk factors were common, with an average of 2.8 per patient (median: 3). Seven patients (37%) had a family history of premature CAD, and four had elevated lipoprotein (a). The mean BMI was 28.6 ± 5.5 kg/m². All CCTA scans were fully diagnostic, despite a mean CAC score of 1509.9 Agatston units.CCTA findings (figure) showed that 74% did not have severe CAD: CAD-RADS 2 (32%), CAD-RADS 3 (42%), CAD-RADS 4 (21%), and CAD-RADS 5 (5%). Fractional flow reserve CT (FFR-CT) was conducted in seven patients all of whom had negative results for functionally significant stenosis. Four patients underwent invasive coronary angiography, including the only CAD-RADS 5 patient, who subsequently underwent coronary artery bypass grafting. Among the remaining three, invasive functional testing in two showed no functionally significant stenosis, and none underwent revascularization (figure). Conclusions PCCT provided reliable diagnostic assessment despite extreme CAC score and has the potential to exclude high risk anatomy and minimize the need for additional testing. Further research is needed to assess its impact on long-term outcomes.

Background Epicardial adipose tissue (EAT) is a metabolically active visceral fat depot that is both a sensor and a modulator of myocardial biology and changes its composition in response to paracrine signals from the myocardium. We hypothesized that radiomic characterization of EAT from routine coronary computed tomographic angiography (CCTA) can noninvasively capture this adverse remodeling and enable early heart failure (HF) risk stratification. Objectives We sought to develop and externally validate a reproducible radiomic signature of EAT associated with incident HF. Methods We conducted a multicenter cohort study of 72,751 adults without known HF or myocardial infarction undergoing CCTA across 9 UK centers (2007-2022). We deployed a fully automated pipeline to segment EAT and extract 1,655 volumetric, shape, and higher-order radiomic texture features. Using a harmonized survival autoencoder architecture, we derived the fat radiomic profile for HF (FRPHF). The model was developed in 59,327 individuals from 7 centers (age 57 ± 13 years, 47.5% female) and externally tested in 13,424 participants from 2 geographically distinct centers (58 ± 12 years, 49.4% female). Survival models were adjusted for age, sex, and conventional risk factors, including coronary artery disease (CAD) severity and EAT volume. Results Over a median follow-up of 5.1 and 4.0 years, 1,737 (2.9%) and 363 (2.7%) participants developed HF in the internal and external validation cohorts, respectively. FRPHF demonstrated robust discrimination (C-statistics: 0.869 [95% CI: 0.850-0.889] internal; 0.850 [95% CI: 0.831-0.870] external). Each 25-percentile increase in FRPHF was associated with a nearly 4-fold higher adjusted HF risk (adjusted HRs: 3.90 [95% CI: 3.13-4.84] internal; 3.79 [95% CI: 3.01-4.76] external; both P < 0.001), with individuals in the highest decile exhibiting a nearly 20-fold higher risk compared with the lowest decile. In the external cohort, addition of FRPHF to conventional risk models, including EAT volume and CAD severity, significantly improved 5-year discrimination (ΔAUC: 0.047; 95% CI: 0.029-0.065) and net reclassification (NRI: 0.39; 95% CI: 0.29-0.48) and suggested net clinical benefit on decision curve analysis. The associations were consistent across demographic subgroups and across the ejection fraction spectrum. Conclusions Automated radiomic phenotyping of EAT from routine CCTA enables scalable, biologically informed stratification of future HF risk before clinical onset, positioning opportunistic imaging-based visceral fat profiling as a potential tool for precision prevention.

Coronary computed tomography angiography plays a pivotal role in the diagnosis, risk stratification, and treatment of patients with known or suspected coronary artery disease. However, conventional computed tomography (CT) technologies are limited by spatial resolution, artifact susceptibility, and radiation exposure. Photon-counting computed tomography (PCCT) introduces substantial technological improvements over conventional CT. This includes improved spatial and contrast resolution, energy discrimination, and reduction of various artifacts. As a result, PCCT enables superior coronary lumen and plaque evaluation, even in complex cases with severe calcification or smaller coronary stents. Beyond the coronary arteries, PCCT offers improved visualization of cardiac anatomy and myocardial tissue characterization with the potential to reduce downstream testing, improve diagnosis and treatment, and ultimately improve clinical outcomes. PCCT is poised to become the dominant technology for cardiovascular CT; however, challenges such as high costs, increased data demands, and a need for more validation, standardized image acquisition, and post-processing protocols remain. This review explores the technical principles of PCCT, its advantages over conventional CT, and its current and potential future applications in cardiac imaging, highlighting opportunities for future research.

BACKGROUND:The SELECT trial demonstrated that semaglutide reduced major adverse cardiovascular events among individuals with cardiovascular disease (CVD) and overweight/obesity without diabetes. We hypothesized that coronary artery disease (CAD) detected by coronary computed tomography angiography (CCTA) identifies individuals with similar cardiovascular risk. OBJECTIVES:The aim of the study was to evaluate the association between CAD severity by CCTA and cardiovascular outcomes among individuals resembling The SELECT (Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes) trial population but without known CVD. METHODS:We included individuals aged ≥45 years with body mass index ≥27 kg/m2 undergoing CCTA at 2 centers. EXCLUSIONS:prior myocardial infarction, revascularization, stroke, diabetes, end-stage kidney disease, or malignancy. CAD severity was categorized as absent (0%), nonobstructive (1%-49%), or obstructive (≥50%). Extensive nonobstructive CAD was defined as plaque in all coronary arteries. Cox modeling assessed the association between CAD and the composite outcome of cardiovascular death, myocardial infarction, or stroke. RESULTS:Among 5,173 individuals, 53% were male, and 68% and 62% had hypertension and dyslipidemia, respectively. Individuals with obstructive CAD had a 71% higher risk of events (adjusted HR: 1.71; 95% CI: 1.21-2.42; P = 0.002) vs those with no CAD. At 4 years, event risks were 7.8% for obstructive CAD and 7.7% for extensive nonobstructive CAD, comparable to SELECT's control arm (9.7%). Applying SELECT's relative rate reduction of 20%, the number needed to treat was 66 for obstructive and 67 for extensive nonobstructive CAD, comparable to SELECT's 56. CONCLUSIONS:Obstructive or extensive nonobstructive CAD by CCTA identifies overweight/obese individuals without diabetes and no prior CVD as being at elevated cardiovascular risk, suggesting potential benefit from glucagon-like peptide-1 receptor agonist therapy.

Background: Neurocognitive impairment is linked to aging, vascular stiffness, and HIV infection. The role of vascular stiffness in neurocognitive functioning among men with HIV (MWH) remains unclear. This study examined the relationship between carotid artery distensibility and neurocognitive decline in MWH and men without HIV (MWoH), while exploring whether HIV serostatus and age influenced the association. Methods: Baseline vascular and cognitive assessments (2004-2013) were measured in the Multicenter AIDS Cohort Study. Carotid distensibility was measured using B-mode ultrasound. Neurocognitive function was assessed via executive function (Trail Making B) and psychomotor/information processing speed (Trail Making A, Symbol Digit Modalities Test) over a 6.5-year follow-up. Mixed effects linear regression was used to evaluate the association between baseline stiffness and the progression of neurocognitive function, with time operationalized as participant age. Models were adjusted for demographic, behavioral, and cardiometabolic risk factors. Results: Among 717 men, (mean age 49.9 years, 62.9% non-Hispanic White), 459 (64%) were MWH. In MWH, lower distensibility (higher stiffness) at baseline was associated with greater neurocognitive decline with increasing age in Trail Making A (β=-0.03, p <0.001) and Trail Making B (β=-0.02, p =0.02), but not in Symbol Digit Modalities Test. Among MWoH, lower distensibility at baseline was associated with greater neurocognitive decline with increasing age in Trail Making B (β=-0.03, p=0.002) only. The longitudinal association of distensibility with neurocognition only differed by HIV serostatus for Trail Making A ( p <0.05), when assessing the three-way interaction of serostatus, age, and distensibility. Conclusions: Increased vascular stiffness was linked to significant neurocognitive decline in both MWH and MWoH after adjusting for confounding factors. Addressing cardiovascular risk factors may help prevent neurocognitive decline in this population.