Since 2020, artificial intelligence (AI) has been increasingly applied to atherosclerotic cardiovascular disease (ASCVD) risk prediction. This structured narrative review with systematic evidence mapping summarizes literature (2020-2026) examining study design, data sources, model architectures, multimodal fusion, model development and validation, performance evaluation, subgroup applications, and implementation barriers. Overall, 126 studies informed the review; 93 provided sufficient information for structured extraction, including prevention setting, exact input variables, comparator scores, validation strategies, discrimination, calibration, dominant model architecture, endpoint category, foundation-model or pretrained-model status, regulatory status, and implementation features. AI-based models may offer modest but clinically meaningful gains over conventional risk equations, especially with multimodal or longitudinal data. Among the 93 studies, traditional machine learning accounted for 83 (89%), deep learning for 7 (8%), and multimodal fusion for 3 (3%). Endpoint definitions were heterogeneous (23% ASCVD-specific; 63% expanded MACE composites). Among these studies, no large language model or federated learning was used for risk prediction. Appropriate comparators should now include contemporary equations such as PREVENT, rather than only legacy tools. Major barriers remain, including limited external validation, performance attenuation, data and algorithmic bias, limited interpretability, inconsistent reporting of calibration, fairness, and clinical utility, unclear regulatory status, and limited prospective evidence. Future work should prioritize calibration, robustness, transportability, fairness, interpretability, regulatory clarity, workflow integration, and prospective evidence of decision impact or post-deployment benefit. The central question is not only whether AI can detect complex patterns, but whether such models can be trusted, implemented, and shown to advance preventive cardiology in real-world settings.
BACKGROUND:Aficamten is a next-in-class, selective cardiac myosin inhibitor (CMI) that relieves left ventricular outflow tract (LVOT) obstruction in obstructive hypertrophic cardiomyopathy (oHCM) by addressing underlying myocardial hypercontractility. The long-term impact of aficamten on myocardial mechanics as measured by global longitudinal strain (GLS) is unknown. METHODS:FOREST-HCM (NCT04219826) is an ongoing open-label extension trial for eligible patients with HCM who completed a parent study of aficamten. Here we report echocardiographic parameters (LVOT gradient and myocardial GLS) obtained from baseline up to week 48 from oHCM patients (N = 27) included in the FOREST-HCM study. RESULTS:From baseline to 38 ± 4.8 weeks, aficamten reduced LVOT gradients at rest (mean difference - 32.7 ± 24 mmHg, p < 0.0001 vs. baseline) and with Valsalva (mean difference - 62.44 ± 34.5 mmHg, p < 0.0001 vs. baseline). Compared to baseline, strain analysis revealed similar GLS at week 12 (-13.9 ± 3.2 vs. -14.3 ± 3.0, p = 0.316) but a significant improvement at weeks 36-48 (-13.9 ± 3.2 vs. -15.1 ± 2.7, p = 0.0093). These improvements were only seen in patients who achieved a hemodynamic response (resting LVOT-G < 30 mmHg, n = 24, p = 0.0009; or complete response with rest <30 mmHg and Valsalva <50 mmHg, n = 21, p = 0.0023). CONCLUSIONS:Aficamten therapy improves myocardial mechanics after long-term treatment, which may indicate functional myocardial improvement incremental to relief of outflow obstruction. The potential mechanisms underlying this improvement warrant further investigation. REGISTRATION:https://clinicaltrials.gov/study/NCT04848506; Clinical trial identifier: NCT04848506.
AIMS:The relative contributions of inflammatory and atherogenic lipoprotein pathways to residual cardiovascular risk remain unclear. We examined the joint and independent associations of interleukin-6 (IL-6) and apolipoprotein B (ApoB) with major adverse cardiovascular events (MACE) and mortality. METHODS:Among 34,064 UK Biobank participants free of prevalent atherosclerotic cardiovascular disease with Olink proteomics, multivariable Cox models estimated hazard ratios (HRs) for MACE (myocardial infarction (MI), stroke, or cardiovascular death), MACE components, and all-cause mortality. Models adjusted for demographics, HDL cholesterol, triglycerides, lipid-lowering therapy, hypertension, diabetes, smoking, eGFR, BMI, and high sensitivity C-reactive protein. Participants were additionally classified into four groups by median IL-6 and an ApoB threshold of 90 mg/dL. RESULTS:Over a median 13.6 years, 2551 (7.5%) MACE events occurred. In continuous models, IL-6 and ApoB were each independently associated with MACE (IL-6 HR 1.11 per SD, 95% CI 1.07-1.16; ApoB HR 1.12 per SD, 95% CI 1.07-1.17), and a simultaneous 1-SD increase in both biomarkers conferred 22% higher MACE risk. Associations were endpoint-specific: ApoB was strongest for MI (HR 1.20, 1.14-1.27), IL-6 for cardiovascular death (HR 1.20, 1.12-1.29) and all-cause mortality (HR 1.17, 1.14-1.20). In categorical analyses, MACE risk rose stepwise relative to the Low IL-6, Low ApoB reference: HR 1.22 (95% CI 1.05-1.41) for high ApoB alone, 1.33 (95% CI 1.15-1.55) for high IL-6 alone, and 1.55 (95% CI 1.34-1.78) for both. CONCLUSION:IL-6 and ApoB were independently associated with cardiovascular events, with atherogenic lipoprotein burden predominating for MI and inflammatory signaling for cardiovascular and all-cause death.
BACKGROUND:Biventricular pacing (BVP) is the standard for cardiac resynchronization therapy (CRT), particularly in left bundle branch block (LBBB). However, conduction system pacing (CSP) may offer superior outcomes as a physiological alternative. We evaluated the clinical efficacy of CSP compared with BVP as a primary strategy for patients with heart failure indicated for CRT. METHODS:A systematic review and meta-analysis was conducted using MEDLINE and the Cochrane Library databases. We included randomized controlled trials (RCTs) comparing CSP with BVP in patients with heart failure and a left ventricular ejection fraction below 50%. Pooled estimates were determined using a random-effects model for all outcomes. RESULTS:Twelve RCTs involving 1223 patients were included. CSP significantly improved the echocardiographic response compared with BVP in the overall cohort (odds ratio [OR]: 1.73; 95% confidence interval [CI]: 1.19-2.52) and the LBBB subgroup (OR: 1.74; 95% CI: 1.15-2.62). CSP revealed significant improvements in NYHA functional class (standardized mean difference: -0.27; 95% CI: -0.46 to -0.08) and 6-min walk distance (mean difference: 21.6 m; 95% CI: 8.07 to 35.14). While composite endpoints (OR: 0.59; 95% CI: 0.33 to 1.08) and mortality (OR: 0.90; 95% CI: 0.39 to 2.11) showed trends favoring CSP, neither reached statistical significance. There was no significant difference in procedural crossovers between the groups (OR: 1.24; 95% CI: 0.54 to 2.87). CONCLUSION:Compared with BVP, CSP improved echocardiographic and functional response in patients requiring CRT. CSP as a primary strategy may be considered in selected patients, but large RCTs with hard clinical endpoints are needed.
Coronary revascularization can be achieved via coronary artery bypass (CABG) or percutaneous coronary intervention (PCI). CABG is associated with higher peri-procedural complications and longer recovery periods but greater long-term reduction in recurrent cardiac events compared to PCI. The preferred revascularization modality depends on various clinical and anatomic factors. In general, CABG is preferable for patients with complex coronary artery disease, especially in cases of concomitant diabetes or reduced left ventricular ejection fraction. Meanwhile, PCI is preferred in patients with less extensive disease or those at high surgical risk. However, patient preference should be a key part of the treatment decision. The majority of randomized evidence is based on primarily White, non-elderly male populations from high-income countries. More robust evidence is urgently needed for patients that are female, older, non-White, and from low- or middle-income countries. In this review, we summarize the current evidence for CABG and PCI, discuss the optimal revascularization strategies for different patient populations, and highlight future directions and knowledge gaps in the field of coronary revascularization.
BACKGROUND:Surgical pulmonary valve replacement (SPVR) is the standard therapy for native or patched right ventricular outflow tract (nRVOT) dysfunction. Transcatheter pulmonary valve replacement (TPVR) has emerged as a less invasive alternative, but comparative data are lacking. OBJECTIVES:To compare clinical outcomes and valve performance between TPVR and SPVR in patients with nRVOT dysfunction. METHODS:Patients with nRVOT dysfunction undergoing TPVR or SPVR were retrospectively identified. TPVR cases were propensity score-matched 1:2 to SPVR. The primary outcome was freedom from all-cause mortality, prosthetic valve endocarditis, or valve-related reintervention. RESULTS:Among 176 patients, 123 (41 TPVR, 82 SPVR) were matched. At 3 years, freedom from the primary outcome was 95.2% for TPVR and 91.5% for SPVR (HR 0.68; 95% CI 0.14-3.29; p = 0.63). TPVR had fewer major in-hospital complications (4.9% vs 18.3%; p = 0.04) and shorter ICU and hospital stays (0.3 ± 0.8 vs 4.8 ± 6.9 days, and 3.1 ± 3.0 vs 12.9 ± 14.6 days; both p < 0.001). Mean gradients were consistently lower with TPVR post-procedure (8.0 vs 9.9 mmHg; p = 0.02), at 1 year (7.9 vs 10.6 mmHg; p = 0.02), and at 3 years (8.4 vs 11.0 mmHg; p = 0.03). Pulmonary regurgitation remained comparable, with most patients having none or mild regurgitation at 3 years (90.0% vs 94.5%; p = 0.22). CONCLUSIONS:In the first propensity score-matched comparison of TPVR and SPVR in nRVOT dysfunction, TPVR demonstrated comparable 3-year clinical outcomes, fewer major in-hospital complications, shorter hospital stay, and more favorable valve hemodynamic performance. These findings support TPVR as an effective, less invasive alternative, although longer-term outcomes warrant further study.
Background Cardiometabolic disease (CMD) and cardiometabolic multimorbidity (CMM) are increasing rapidly, particularly among younger adults. This study aimed to quantify associations of age at CMD/CMM diagnosis with mortality risk and life expectancy. Methods A total of 684,218 participants from six cohorts (UK Biobank, US NHANES, SHARE, CHARLS, CMEC, and ELSA) were included. CMD was defined as the presence of cardiovascular disease (CVD), hypertension, or diabetes. Cox proportional hazard models were used to estimate hazard ratios (HRs) for all-cause and cause-specific mortality according to age at CMD diagnosis. Life expectancy reduction were further evaluated by age of diagnosis. Results Earlier CMD diagnosis showed a clear dose–response association with higher mortality across cohorts. In the UK Biobank, the HR (95% CI) for all-cause mortality was 5.91 (4.95–7.06) for diagnosis before age 40, declining to 1.37 (1.33–1.41) at ≥70 years. Similar trends were observed in other cohorts. Earlier CMD diagnosis were also associated with greater life expectancy reduction. For instance, among 60-year-olds in the UK Biobank, those diagnosed before age 40, at 40–49, and at 50–59 years lost approximately 9.3, 5.4, and 3.2 years, respectively. For multimorbidity, mortality risk and years of life lost increased with the number of CMDs. Participants with coexisting CVD and hypertension diagnosed before age 40 had the highest mortality risk [7.36 (5.09–10.63)] and lost about 9.6 years of life at age 60. Conclusions Earlier diagnosis of CMD and CMM is strongly associated with elevated mortality and substantial reductions in life expectancy. These findings underscore the importance of early preventive intervention strategies to delay disease onset and mitigate premature mortality.
Longevity is a relevant cardiovascular (CV) endpoint because survival integrates incident CV disease (CVD), competing non-CVD risks, and the physiological reserve that determines resilience to aging and chronic illness. Two related constructs, physical activity (PA; a modifiable behavior) and cardiorespiratory fitness (CRF; an integrative phenotype reflecting habitual PA, genetics, cardiopulmonary function, skeletal muscle oxidative capacity, and comorbidity), are consistently associated with lower all-cause and CVD mortality across diverse populations. In this invited narrative review, we synthesize evidence linking PA and CRF to longevity, highlight the dose-response nature of benefits and the importance of activity domain and intensity, and explain why CRF generally outperforms self-reported PA for risk prediction. We address challenges in causal inference, residual confounding variables, reverse causation, and selection/measurement bias, and emphasize approaches that strengthen inference, including device-based PA assessment (e.g., accelerometry), repeated measures, and triangulation with mechanistic and trial evidence. Mechanistic pathways plausibly linking PA and CRF to survival include favorable effects on blood pressure, glycemia and insulin sensitivity, adiposity and body composition, vascular reactivity, autonomic balance, inflammation and immune function, thrombosis, and preservation of skeletal muscle and mitochondrial reserve. We review evidence in particularly relevant subgroups and discuss the "extreme exercise hypothesis", distinguishing mortality from risks, such as atrial fibrillation and accelerated coronary calcification, in endurance athletes. We conclude with practical actions for clinicians and health systems, such as prescribing activities based on the frequency, intensity, time, and type (FITT) principles, incorporating resistance training, treating CRF as a vital sign, and addressing common implementation barriers.
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.
The landscape of lipid management has transitioned from a statin-monotherapy and statin-intensification paradigm to a sophisticated, multi-axis intervention model targeting low-density lipoprotein cholesterol, triglyceride-rich lipoproteins, lipoprotein(a), and vascular inflammation. The emergence of PCSK9-targeted small interfering RNA therapies, CETP inhibitors, and Lp(a)-directed antisense and RNA based agents has enabled complementary modulation of diverse lipid pathways through distinct molecular targets. However, this increasingly multidrug approach may also increase treatment complexity, healthcare burden, and adherence challenges, particularly among high-risk patients already receiving multidrug cardiometabolic therapy. Although intensive and sustained LDL-C lowering remains foundational to preventive cardiology, the real-world effectiveness of increasingly complex treatment strategies may ultimately depend on long-term adherence, affordability, patient capacity, and implementation feasibility. We propose a Clinical Prioritization and Personalization Framework centered on individualized risk-based intensification, comprehensive residual risk management, and optimization of treatment delivery to achieve sustainable, patient-centered cardiovascular protection.
AIMS:Lower socioeconomic position (SEP) groups have higher risks of cardiovascular diseases (CVD), with diet quality being a crucial risk factor. However, whether the association between diet quality and incident CVD differs across SEP (education and income) groups is unclear, which was examined in this study. METHODS:This study included participants aged 30-80 years, free of CVD at baseline, from the Dutch Lifelines cohort. The Lifelines Diet Score, a diet quality indicator based on Dutch dietary guidelines, was calculated with data assessed by a 110-item food frequency questionnaire. Cox proportional hazards models were used to assess the association between diet quality and incident CVD (the first non-fatal major cardiovascular event), and whether this association was modified by SEP, adjusted for age, sex, energy intake, alcohol intake, smoking, TV watching time, moderate-to-vigorous physical activity, sleep duration, social/hobby clubs participation, chronic stress, family history of CVD, and BMI. RESULTS:Of 82,360 participants included, 2827 incident CVD cases were identified (median follow-up 7.4 years, incidence rate 4.7 per 1000 person-years). Education modified the association between diet quality and incident CVD (P-interaction = 0.033). Comparing the poorest to the best diet quality quartiles, hazard ratios (95%CI) were 1.27 (1.06, 1.51) in low, 1.28 (1.06, 1.54) in middle, and 0.98 (0.76, 1.27) in high education group. CONCLUSIONS:For low- and middle-education groups, poor diet quality was associated with disproportionately higher risks of incident CVD. Improving diet quality may therefore have the potential to be a core entry point for lowering CVD health inequalities. To address persistent health inequalities, health policies should tackle broader environmental, social, and structural factors of diet and health equity.
