AIMS:The prevalence and long-term prognostic significance of coronary atherosclerosis detected by coronary computed tomography angiography (CCTA) in young adults remain insufficiently defined. We aimed to evaluate the prevalence of coronary atherosclerosis and its association with long-term cardiovascular outcomes among young adults undergoing clinically indicated CCTA. METHODS AND RESULTS:We performed a retrospective cohort study of consecutive patients undergoing CCTA at two academic centres between 2006 and 2021. Patients with prior coronary artery disease, end-stage renal disease, or malignancy were excluded. Young adults were defined as men ≤50 years and women ≤60 years. Coronary artery disease (CAD) was classified as no CAD, non-obstructive plaque (1-49% stenosis), or obstructive CAD (≥50% stenosis). The primary outcome was a composite of cardiovascular death, non-fatal myocardial infarction, or ischaemic stroke. Associations between CAD severity and outcomes were assessed using cause-specific proportional hazards models with multivariable adjustment. Among 10,247 young adults (median age 47 years; 56% women), 29.0% had non-obstructive plaque and 8.7% had obstructive CAD. Over a median follow-up of 6.7 years (interquartile range 4.2-10.4), the risk of the primary outcome increased with increasing CAD severity. Compared with no CAD, obstructive CAD was associated with a more than two-fold higher risk of events [adjusted hazard ratio (HR) 2.6, 95% confidence interval (CI) 1.9-3.6], while non-obstructive CAD was associated with a modest, non-significant increase in risk (adjHR 1.2, 95% CI 0.9-1.7). Among patients with non-obstructive CAD, event rates increased with greater plaque extent. CONCLUSION:In routine clinical practice, approximately 40% of young adults undergoing CCTA demonstrate coronary atherosclerosis, which is independently associated with adverse long-term cardiovascular outcomes. These findings support the role of CCTA in early risk stratification and targeted preventive strategies among younger individuals.

BACKGROUND:Although the prognostic utility of positron emission tomography (PET) myocardial flow reserve (MFR) is well established, emerging data suggest that reduced subendocardial flows also predict adverse outcomes. However, the incremental value of subendocardial MFR (MFRSE) beyond transmural MFR (MFRTM) remains unclear. METHODS:We studied patients in a multicenter PET registry with normal perfusion on stress/rest Rb-82 PET, excluding those with a previous history of coronary artery bypass surgery, heart transplantation, or left ventricular ejection fraction <40%. The optimal MFRSE cutoff for predicting major adverse cardiovascular events (MACEs; death, myocardial infarction [MI], revascularization, or heart failure [HF] hospitalization) was determined using Youden's index. Patients were stratified into 3 groups: concordant-normal (MFRTM ≥2.0; MFRSE ≥2.1), discordant (low-MFRSE, normal MFRTM), and abnormal MFRTM. Clinical outcomes were compared by MFR groups. RESULTS:Among 6603 patients (normal N=4103; discordant N=885; abnormal N=1615) the mean age was 66.3±12.4 years, and 54% were women. Compared with the concordant-normal group, patients with discordant low-MFRSE were older and more likely to have hypertension, diabetes, peripheral artery disease, and previous percutaneous coronary intervention. The median MFRTM for normal, discordant, and abnormal groups were 2.86, 2.15, and 1.72, respectively. Over a median follow-up of 4.9 years, 1661 MACE events occurred. Discordant low-MFRSE patients had a higher risk of MACE (hazard ratio [HR], 1.41; 95% CI, 1.22-1.64) and all-cause mortality (HR, 1.36; 95% CI, 1.14-1.61) compared with concordant-normal patients. The discordant group had an intermediate absolute risk of MACE, with an adjusted annualized event rate of 5.79% (95% CI, 5.10-6.49) compared with 3.99% (95% CI, 3.67-4.30; P<0.001) in the concordant-normal group and 8.35% (95% CI, 7.71-9.00; P<0.001) in the abnormal MFRTM group. CONCLUSIONS:Subendocardial MFR reveals clinically meaningful risk heterogeneity among patients with preserved transmural flow reserve, helping refine risk stratification beyond traditional PET metrics.

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) remodelling. 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 remodelling and function in patients with and without LBBB. METHODS AND RESULTS:We analysed 233 patients with LBBB and 932 matched controls who underwent PET myocardial perfusion imaging, assessing mechanical dyssynchrony (phase entropy), LV volumes, and ejection fraction (EF); coronary vascular resistance (CVR), myocardial blood flow (MBF), myocardial flow reserve (MFR) as markers of microvascular function; and septal-to-lateral MBF ratio (SLR) as a measure of regional perfusion heterogeneity. Compared with controls, LBBB patients had greater dyssynchrony (56% vs. 40%), larger LV volumes, and lower EF (54% vs. 67%) (all P < 0.001), as well as higher stress CVR (37 vs. 34 mmHg/mL·min-1·g-1), and lower MBF (2.4 vs. 2.6 mL/min/g), MFR (2.4 vs. 2.6), and SLR (0.95 vs. 1.00) (all P < 0.05). Among patients with dyssynchrony, SLR <1.0 identified greater remodelling. 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 Cox 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 death or heart failure hospitalization, whereas LBBB was not. CONCLUSION:Mechanical dyssynchrony and perfusion heterogeneity independently predict adverse LV remodelling, irrespective of LBBB. Integrated imaging improves cardiomyopathy stratification.

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.

Positron emission tomography (PET)/computed tomography (CT) for myocardial perfusion imaging (MPI) provides multiple imaging biomarkers, often evaluated separately. We developed an artificial intelligence (AI) model integrating key clinical PET MPI parameters to improve the diagnosis of obstructive coronary artery disease (CAD). From 17,348 patients undergoing cardiac PET/CT across four sites, 1664 with invasive coronary angiography and no prior CAD were retrospectively analyzed. Coronary artery calcium (CAC) scores were derived from CT attenuation correction maps, and XGBoost model was trained on one site using 10 image-derived parameters: CAC, stress/rest left ventricular ejection fraction, stress myocardial blood flow (MBF), myocardial flow reserve (MFR), ischemic and stress total perfusion deficit (TPD), transient ischemic dilation ratio, rate pressure product, and sex. External validation was performed across three independent sites. In the testing cohort (n = 1278; CAD prevalence 53

Background Clinical adoption of cardiovascular magnetic resonance (CMR) is hampered by procedural complexity and magnetic resonance imaging access. Objectives The objective of the study was to investigate the benefits of artificial intelligence (AI)-assisted CMR in clinical practice. Methods Patients at a tertiary-care center underwent CMR via conventional, operator-directed (ODS) or AI-assisted (AIA) scanning over 3 years. Scan time, scan time variation, image quality using a validated 5-point scale, scan failure, and survival were compared between groups, stratified across CMR indications and technologists’ experience. Results From 2020 to 2024, 6,080 consecutive patients (age 57 ± 17 years, 55% males) underwent 6,545 studies (1,635, 25% AIA, 4,910, 75% ODS) for 5 primary indications. Average scan time and its coefficient of variation were reduced by 23% and 31%, respectively, with AIA compared to ODS (37.9 ± 6.9 vs 49.2 ± 13.0 min; P < 0.001). Scan time reduction by AIA was consistent across indications and range of technologists’ experience, and remained significant after adjusting for key demographic and clinical differences (P < 0.0001) or propensity score. Scan quality score was higher in AIA for cine images (4.09 ± 0.8 vs 4.03 ± 0.8; P < 0.001), late gadolinium enhancement (4.08 ± 0.8 vs 3.98 ± 0.7; P < 0.001), and perfusion (4.28 ± 0.6 vs 4.14 ± 0.6; P < 0.001). Scan failure leading to 90-day repeat CMR was lower in AIA compared to ODS (0.6% vs 1.4%, P < 0.001). After its introduction in 2021, AIA use progressively increased to 78% by 2023. At a median follow-up of 29 months, patient survival did not differ between groups (log-rank P = 0.500). Conclusions In this nonrandomized comparison, AIA improved scan time, scan time consistency, image quality, and 90-day scan failure across top CMR indications, compared to ODS.

This study aimed to assess the relationship between coronary CT angiography detected coronary artery disease (CAD) and long-term cardiovascular outcomes among individuals with and without diabetes mellitus (DM). A retrospective cohort study of patients undergoing CCTA at two medical centers between 2006 and 2024. Patients with prior CAD, advanced kidney disease, or malignancy were excluded. DM was defined by diagnostic codes or elevated hemoglobin A1c. CCTA findings were categorized as no CAD, nonobstructive CAD (1–49

BACKGROUND:Physiologic interaction between the cardiovascular and renal systems is pivotal in the understanding of disease and as a target for therapeutic interventions, as highlighted in the cardiovascular-kidney-metabolic syndrome. This study explores the association of renal blood flow, derived noninvasively from cardiac positron emission tomography-computed tomography, with cardiovascular and renal outcomes. METHODS:We evaluated the association between renal blood flow and outcomes in a retrospective cohort of 295 consecutive patients who underwent 13N-ammonia positron emission tomography-computed tomography myocardial perfusion imaging between September 1, 2019, and March 1, 2020 (Brigham and Women's Hospital, Boston). Global myocardial blood flow, myocardial flow reserve, semiquantitative coronary artery calcium, and previously validated resting renal blood flow were obtained, along with clinical and laboratory data. Patients were followed for 4.0 (interquartile range, 1.7-4.1) years for a composite cardiovascular outcome of all-cause mortality, heart failure hospitalization, or acute coronary syndrome, and a composite renal outcome of 25% reduction in estimated glomerular filtration rate or end-stage renal disease. Survival analyses were adjusted for demographic and clinical characteristics and additionally for estimated glomerular filtration rate and myocardial flow reserve. RESULTS:The population had a mean age of 65.6 years, a body mass index of 29.2 kg/m2, and was 49% female. Overall, 36% had chronic kidney disease stage ≥3. Patients were stratified into 3 renal blood flow groups: ≥75%, 25 to 75th, and ≤25% percentile. Lower renal blood flow was significantly associated with a higher risk of cardiovascular events (adjusted hazard ratio, 5.21 [95% CI 1.53-17.75]; P=0.008; lowest versus highest quartile), and with an elevated risk of adverse renal outcomes (P=0.026), independent of estimated glomerular filtration rate and myocardial flow reserve. CONCLUSIONS:Impaired renal blood flow is associated with cardiac and kidney events, independent of the highly prognostic estimated glomerular filtration rate and myocardial flow reserve. Simultaneous quantification of cardiac and renal perfusion by noninvasive 13N-ammonia positron emission tomography-computed tomography may provide a valuable tool to interrogate pathophysiology and prognosis in the cardiovascular-kidney-metabolic syndrome.

BACKGROUND:Recent guidelines suggest that coronary computed tomography angiography (CTA) may be the preferred testing modality in patients <65 years of age who are suspected of having coronary artery disease (CAD). Because of a higher prevalence of CAD, the role of coronary CTA in older cohorts is less well established. OBJECTIVES:The authors aimed to characterize the yield and prognostic utility of coronary CTA by age in a large registry with long-term follow-up. METHODS:Retrospective cohort of patients clinically referred to coronary CTA at 2 medical centers from 2006 to 2021, excluding patients with prior CAD, severe renal disease, and malignancy. Adjusted Cox regression was used to assess the association of CAD severity (absent, nonobstructive, obstructive) and extent (number of vessels with plaque) with adverse cardiovascular events (major adverse cardiovascular events [MACE]: cardiovascular death, nonfatal myocardial infarction, or ischemic stroke) across different age groups. RESULTS:Among 22,412 patients followed over a median of 6.2 years (Q1-Q3: 3.9-9.6 years), 16,726 were <65 years of age and 5,686 were ≥65 years of age. Older patients had a higher prevalence of obstructive CAD (38% vs 15%) and extensive plaque (52% vs 20% with 3- to 4-vessel involvement) compared with their younger counterparts. Nonobstructive plaque was common in both groups (<65 years of age: 37%; ≥65 years of age: 48%). Obstructive CAD was associated with MACE in both younger (HR: 2.45; P < 0.001) and older individuals (HR: 1.97; P < 0.001). Nonobstructive plaque was associated with MACE in younger individuals (HR: 1.39; P = 0.005), whereas only extensive nonobstructive CAD was associated with MACE in older individuals (HR: 1.56; P = 0.02). Among those with obstructive CAD on coronary CTA who underwent early invasive coronary angiography, revascularization was less common among older adults (48% vs 56%; P = 0.002). CONCLUSIONS:In a large coronary CTA registry, patients ≥65 years of age were more likely to have extensive plaque and stenosis. Although the prognostic value of coronary CTA may be lower among older adults with nonobstructive plaque (a group that has a similar event rate as those with no CAD), the presence of extensive nonobstructive plaque or obstructive stenosis was independently associated with a significantly higher rate of MACE. Newer techniques to better risk stratify patients with nonobstructive plaque may improve the value of coronary CTA, especially in older adults.

BACKGROUND AND AIMS:Skeletal muscle (SM) fat infiltration, or intermuscular adipose tissue (IMAT), reflects muscle quality and is associated with inflammation, a key determinant in cardiometabolic disease. Coronary flow reserve (CFR), a marker of coronary microvascular dysfunction (CMD), is independently associated with body mass index (BMI), inflammation and risk of heart failure, myocardial infarction, and death. The relationship between SM quality, CMD, and cardiovascular outcomes is not known. METHODS:Consecutive patients (n = 669) undergoing evaluation for coronary artery disease with cardiac stress positron emission tomography demonstrating normal perfusion and preserved left ventricular ejection fraction were followed over a median of 6 years for major adverse cardiovascular events (MACEs), including death and hospitalization for myocardial infarction or heart failure. Coronary flow reserve was calculated as stress/rest myocardial blood flow. Subcutaneous adipose tissue (SAT), SM, and IMAT areas (cm2) were obtained from simultaneous positron emission tomography attenuation correction computed tomography using semi-automated segmentation at the 12th thoracic vertebra level. RESULTS:Median age was 63 years, 70% were female, and 46% were nonwhite. Nearly half of patients were obese (46%, BMI 30-61 kg/m2), and BMI correlated highly with SAT and IMAT (r = .84 and r = .71, respectively, P < .001) and moderately with SM (r = .52, P < .001). Decreased SM and increased IMAT, but not BMI or SAT, remained independently associated with decreased CFR (adjusted P = .03 and P = .04, respectively). In adjusted analyses, both lower CFR and higher IMAT were associated with increased MACE [hazard ratio 1.78 (95% confidence interval 1.23-2.58) per -1 U CFR and 1.53 (1.30-1.80) per +10 cm2 IMAT, adjusted P = .002 and P < .0001, respectively], while higher SM and SAT were protective [hazard ratio .89 (.81-.97) per +10 cm2 SM and .94 (.91-.98) per +10 cm2 SAT, adjusted P = .01 and .003, respectively]. Every 1% increase in fatty muscle fraction [IMAT/(SM + IMAT)] conferred an independent 2% increased odds of CMD [CFR <2, odds ratio 1.02 (1.01-1.04), adjusted P = .04] and a 7% increased risk of MACE [hazard ratio 1.07 (1.04-1.09), adjusted P < .001]. There was a significant interaction between CFR and IMAT, not BMI, such that patients with both CMD and fatty muscle demonstrated highest MACE risk (adjusted P = .02). CONCLUSIONS:Increased intermuscular fat is associated with CMD and adverse cardiovascular outcomes independently of BMI and conventional risk factors. The presence of CMD and SM fat infiltration identified a novel at-risk cardiometabolic phenotype.