搜索结果：Journal of the American College of Cardiology

Cardiovascular disease increases risks of chronic kidney disease (CKD) progression and mortality in type 2 diabetes. The study sought to assess semaglutide effects on kidney and survival outcomes by baseline cardiovascular status in the FLOW trial. Participants with type 2 diabetes and CKD were randomized to once-weekly subcutaneous semaglutide 1.0 mg vs placebo. Baseline subgroups included atherosclerotic cardiovascular disease (ASCVD), heart failure, and high total cardiovascular disease risk without established cardiovascular disease (10-year PREVENT [Predicting Risk of cardiovascular disease EVENTs] score &#x2265;20%). The primary outcome was &#x2265;50% estimated glomerular filtration rate (eGFR) decline, eGFR <15 mL/min/1.73 m2, dialysis, transplantation, and kidney or cardiovascular death. All-cause death was a confirmatory secondary outcome. At baseline, 1,198 (33.9%) of 3,533, 678 (19.2%) of 3,532, and 1,329 (66.5%) of 2,000 participants had ASCVD, heart failure, or high total cardiovascular disease risk in those without established cardiovascular disease, respectively. Semaglutide reduced the primary outcome risk in subgroups with (119 of 593 vs 146 of 605) or without (212 of 1,174 vs 264 of 1,161) ASCVD (HR: 0.80; 95% CI: 0.63-1.02; and HR: 0.74; 95% CI: 0.62-0.89, respectively; P for interaction = 0.62), with (67 of 342 vs 88 of 336) or without (264 of 1,424 vs 322 of 1,430) heart failure (HR: 0.67; 95% CI: 0.49-0.93; and HR: 0.79; 95% CI: 0.67-0.93, respectively; P for interaction = 0.40), and with (134 of 675 vs 168 of 654) or without (44 of 331 vs 58 of 340) high total cardiovascular disease risk (HR: 0.73; 95% CI: 0.58-0.91; and HR: 0.73; 95% CI: 0.49-1.08, respectively; P for interaction = 0.99). Numbers needed to treat to prevent 1 primary kidney outcome at 3 years were 22, 13, and 17 in the ASCVD, heart failure, and PREVENT score &#x2265;20% subgroups, respectively. Semaglutide also reduced risks of all-cause death with (99 of 593 vs 121 of 605) or without (128 of 1,174 vs 158 of 1,161) ASCVD (HR: 0.82; 95% CI: 0.63-1.07; and HR: 0.78; 95% CI: 0.62-0.99, respectively; P for interaction = 0.79), with (64 of 342 vs 79 of 336) or without (163 of 1,424 vs 200 of 1,430) heart failure (HR: 0.75; 95% CI: 0.54-1.05; and HR: 0.81; 95% CI: 0.66-0.99, respectively; P for interaction = 0.74), and with (73 of 675 vs 98 of 654) or without (23 of 331 vs 28 of 340) high total cardiovascular disease risk (HR: 0.71; 95% CI: 0.52-0.95; and HR: 0.82; 95% CI: 0.47-1.43, respectively; P for interaction = 0.63). Semaglutide improved kidney and survival outcomes in type 2 diabetes with CKD, irrespective of established ASCVD, heart failure, or high total cardiovascular disease risk. (Evaluate Renal Function with Semaglutide Once Weekly [FLOW]; NCT03819153).

Although mitral transcatheter edge-to-edge repair (MTEER) was approved for secondary mitral regurgitation after the COAPT trial, findings of other MTEER trials have been mixed, raising questions about the applicability of the COAPT results to contemporary clinical practice. We used transportability methods to estimate the treatment effects of COAPT trial interventions applied to 2 target populations: 1) trial-eligible patients representative of U.S. clinical practice; and 2) treatment-candidate patients with secondary mitral regurgitation representative of U.S. clinical practice, regardless of trial eligibility. We identified patients from the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy (TVT) Registry who were treated with MTEER for secondary mitral regurgitation from March 14, 2019 to September 30, 2023. To select trial-eligible individuals, we applied COAPT trial eligibility criteria to the TVT Registry sample. We used inverse odds of participation weighting to standardize patient-level COAPT data to the data distribution of each target population sample and estimated treatment-specific outcomes. The primary outcome was heart failure hospitalization at 2 years. We also examined 10 secondary outcomes, including all-cause death. Our analyses included 614 COAPT trial patients and 15,275 TVT Registry patients, of which 7,289 were COAPT trial-eligible. Trial-eligible TVT Registry patients were less likely to have ischemic cardiomyopathy (34.1% vs 60.8%) and more likely to have 4+ mitral regurgitation (79.4% vs 47.9%) compared with trial patients. We estimated that compared with medical therapy alone, MTEER in conjunction with other COAPT interventions (eg, optimization of medical therapy) in the trial-eligible population would result in 2-year absolute risk reductions of 17.0% for heart failure hospitalizations (95% CI: -28.7% to -5.7%) and 15.4% for all-cause death (95% CI: -26.6% to -5.2%), effect sizes similar to those estimated in the trial (P for difference between the trial and target populations >0.05 for both outcomes). The estimated treatment effect for heart failure hospitalizations in the broader treatment-candidate target population was also similar to that in the COAPT trial (P for difference = 0.90). Although COAPT trial patients had different baseline characteristics than patients undergoing MTEER in contemporary U.S. practice, we estimated that treatment effects would be similar had real-world patients received COAPT trial interventions, under the assumptions required for transportability (eg, conditional exchangeability across data sources, positivity of trial participation).

The "2026 AHA/ACC/ADA/ASN Guideline for the Prevention, Detection, Evaluation, and Management of Cardiovascular-Kidney-Metabolic Syndrome" retires, replaces, and expands upon the "2013 AHA/ACC/TOS Guideline for the Management of Overweight and Obesity in Adults." The primary intended audience for this guideline is clinicians who care for patients across the spectrum of cardiovascular-kidney-metabolic syndrome, an interrelated condition characterized by the interconnections among metabolic risk factors (including obesity and type 2 diabetes), chronic kidney disease, and cardiovascular disease. A comprehensive literature search was conducted from October 29, 2024, to April 14, 2025, to identify clinical studies, systematic reviews and meta-analyses, and other evidence conducted on human subjects that were published since 2015 in English from MEDLINE (through PubMed), EMBASE, the Cochrane Library, the Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline. The focus of this clinical practice guideline is to create a living, working document that provides current knowledge in the field of cardiovascular-kidney-metabolic syndrome aimed at all practicing cardiologists, endocrinologists, nephrologists, and primary care and specialty clinicians who manage these patients.

The recent introduction of cardiac myosin inhibitors has modified the therapy of left ventricular outflow obstruction in patients with hypertrophic cardiomyopathy (HCM) and is raising uncertainties regarding the future role of surgery in the management of obstructive HCM. However, it is likely that a proportion of patients will continue to present with advanced, highly symptomatic HCM, despite medical therapy, and require surgical intervention. We previously reported the short-term results of cutting anterior mitral leaflet secondary chordae in combination with septal myectomy in patients with obstructive HCM. This operative approach has shown excellent results in several short-term studies from our and other centers. However, no data are currently available regarding the long-term outcome of this novel surgical procedure. The study sought to investigate the long-term results of myectomy associated with chordal cutting. Long-term results were assessed in 350 consecutive patients with obstructive HCM who underwent this operation at our center over a 5-year period. Median follow-up was 5.6 years (Q1-Q3: 4.2-6.3 years). Including 2 in-hospital deaths (surgical mortality 0.6%), 6-year overall survival after surgery was 96% and did not differ from that of the general Italian population matched for age and sex (P = 0.331). Follow-up information was available in 344 (99%) patients. At the most recent evaluation, 271 (79%) patients were asymptomatic in NYHA functional class I, 65 (19%) were in NYHA functional class II, and 8 (2%) were in NYHA functional class III. During follow-up, there were 14 deaths, 6 of which were unrelated to HCM. At most recent echocardiographic evaluation, &#x2265;95% of patients had no residual left ventricular outflow gradient, clinically significant mitral regurgitation, or impaired systolic function. Our results show that cutting thickened and/or retracted secondary chordae of the anterior mitral leaflet in association with septal myectomy has excellent long-term clinical and hemodynamic results in patients with obstructive HCM. These findings may further increase the number of myectomy referral centers and the availability of the surgical option for severely symptomatic HCM patients unresponsive to medical treatment.

Valvular heart disease (VHD) is associated with substantial morbidity, mortality, and health care costs, yet its contemporary prevalence among older adults in the United States is unknown. We performed a decentralized study of older adults (PREVUE-VALVE) to determine the population prevalence of VHD among older Americans. Individuals 65-85 years old who previously filled a prescription at CVS or Walgreens pharmacies were randomly selected; contacted via e-mail, direct mail, or text messaging; and invited to participate. Enrolled participants completed study procedures in their homes, including a comprehensive transthoracic echocardiogram. The primary endpoint was the prevalence of moderate or greater (&#x2265; moderate) VHD, weighted to reflect the U.S. The co-primary endpoint was the prevalence of clinically significant VHD, which also included mild-to-moderate regurgitant disease. The study sample (n = 3,000) was representative of older Americans (median age 71 years, 57.1% female, 14.6% non-Hispanic Black, 9.4% Hispanic). The weighted prevalence of &#x2265; moderate VHD was 8.2% (95% CI: 7.0%-9.5%), which increased to 18.4% (95% CI: 16.7%-20.2%) for clinically significant VHD. Tricuspid regurgitation was the most common lesion, followed by aortic stenosis, mitral regurgitation, aortic regurgitation, and mitral stenosis. Older age, but not sex, was associated with greater prevalence. In age- and sex-adjusted analyses, non-Hispanic Black individuals had a lower prevalence of any VHD compared with non-Hispanic White individuals (adjusted RR: 0.91; 95% CI: 0.83-0.99), driven predominantly by lower rates of aortic stenosis and regurgitation. There were no significant adjusted differences in VHD prevalence between Hispanic and non-Hispanic individuals. Extrapolation of these data to the U.S. population indicates that at least 4.7 million 65-85-year-olds currently have &#x2265; moderate VHD, and 10.6 million currently have clinically significant VHD-values that are projected to increase to 6.5 and 14.7 million, respectively, by 2060. In this national in-home echocardiography study, VHD was common among older adults, with important age-related and valve-specific patterns. PREVUE-VALVE establishes the feasibility of large-scale decentralized cardiovascular imaging studies and provides a contemporary foundation for clinical and policy planning related to the burden of VHD. (Age- and Sex-Specific Prevalence of Acquired Valvular Heart Disease (PREVUE-VALVE; NCT05357404).

The nonsteroidal mineralocorticoid receptor antagonist finerenone has been shown to improve cardiovascular and kidney outcomes in patients with cardio-kidney-metabolic (CKM) syndrome, but its effects on sudden death (SD) are uncertain. We investigated independent predictors of SD and treatment effects of finerenone on SD. In this prespecified FINE-HEART analysis, we pooled participant-level data from 3 placebo-controlled trials of finerenone in CKM syndrome, including 2 trials of chronic kidney disease with type 2 diabetes (FIDELIO-DKD [Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease] and FIGARO-DKD [Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease]) and a trial of heart failure with mildly reduced ejection fraction/heart failure with preserved ejection fraction (FINEARTS-HF [FINerenone trial to investigate Efficacy and sAfety superioR to placebo in paTientS with Heart Failure]). SD in each trial was centrally adjudicated by a blinded clinical endpoint committee. We identified clinical predictors of SD in multivariable Cox regression models and examined treatment effects of finerenone on SD in Cox models stratified by region and trial. Of the 18,991 participants, 418 (2.2%) (0.77 per 100 patient-years) experienced SD during a median follow-up of 2.9 years. Overall, rates of SD were higher in FINEARTS-HF than in the chronic kidney disease trials (1.5 vs 0.5 per 100 patient-years). For the pooled population, higher risk of SD was associated with older age, history of heart failure, atrial fibrillation, prior myocardial infarction, higher urine albumin-to-creatinine ratio, and lower baseline systolic blood pressure. Randomization to finerenone reduced the risk of SD compared with placebo (HR: 0.81; 95% CI: 0.67-0.98; P = 0.034). Relative risk reductions were consistent across subgroups defined by number of baseline CKM conditions (Pinteraction = 0.93) and trial (Pinteraction = 0.71). The nonsteroidal mineralocorticoid receptor antagonist finerenone was associated with a lower risk of SD across the CKM spectrum. (FINE-HEART: An Integrated Pooled Analysis of Finerenone across 3 Phase III Trials of Heart Failure and Chronic Kidney Disease and Type 2 Diabetes; CRD42024570467).

Academic cardiovascular medicine has driven transformative advances in prevention, diagnosis, and treatment, contributing to substantial declines in cardiovascular morbidity and mortality over the past half century. These achievements have depended on a robust academic workforce integrating clinical care, research, education, and innovation. However, the sustainability of this workforce is increasingly threatened. Early-career academic cardiologists now enter practice amid rising clinical demands, widening compensation disparities, constrained federal research funding, prolonged training pathways, and escalating administrative burden. Concurrently, academic medical centers face financial pressures, often prioritizing short-term clinical revenue over long-term academic investment, disproportionately affecting early-career faculty and jeopardizing the future pipeline of academic leaders. In response to this challenge, the Association of Professors of Cardiology convened a group of emerging early-career academic faculty to identify core challenges facing early-career faculty and developed a roadmap to revitalize academic cardiovascular medicine. This Perspective outlines guiding principles, domains of action, and actionable strategies to help strengthen the academic cardiology workforce. Ensuring that a pipeline of early-career cardiologists who can pursue fulfilling, impactful, and sustainable academic careers that benefit patients and populations is mission central to the future of cardiovascular medicine.

Epigenetic modifications have been linked to atherosclerotic cardiovascular disease and could constitute therapeutic targets. In this study, we sought to identify differentially methylated CpG sites related to atherosclerosis across vascular beds, and to investigate to what extent these epigenetic signatures reflect cardiovascular risk factors (CVRFs). Blood DNA methylation at 767,735 CpG sites was investigated in 3,688 individuals from 2 prospective cohort studies to create a comprehensive atlas of epigenetic modifications in carotid, coronary, and peripheral atherosclerosis. Atherosclerosis was objectively assessed by medical diagnoses, ultrasonography-assessed carotid plaque presence, and ankle-brachial index. Epigenome-wide association studies (EWAS) with 5% false discovery rate correction were performed to explore the relationship between DNA methylation patterns and atherosclerosis, as well as with CVRFs. Methylation scores were trained with the use of ridge regression for each atherosclerosis phenotype in one cohort, and evaluated for discriminatory and prognostic ability in a separate cohort. The influence of CVRFs on atherosclerosis-associated methylation was investigated by: 1) quantification of overlapping CpG sites associated with CVRFs in EWAS; and 2) observing the effect of CVRF trait adjustment on estimates and P values. Totals of 1,687, 3,131, and 5,852 CpG sites were significantly associated with, respectively, carotid, coronary, and peripheral atherosclerosis; 2,155 sites were significantly associated in 2 or more settings. The most strongly associated CpG sites across phenotypes mapped to 4 loci-an intergenic region on chromosome 2 (near ALPP/ALPG), AHRR, PRSS23, and F2RL3-with additional strong signals in ABCG1 and DHCR24 in coronary atherosclerosis. Epigenetic scores were predictive of 3-point major adverse cerebrovascular and cardiovascular events (HRs ranging from 1.23 to 1.39; all P < 0.001). Overall, >90% of atherosclerosis-associated CpG sites intersected with CVRF-associated sites, particularly smoking (up to 90%), followed by inflammation (60%) and metabolic traits (44%). Atherosclerosis EWAS adjustment for smoking pack-years alone reduced the median absolute estimate of significant CpG sites by 19.6% to 29.0%, and joint adjustment for all CVRF markers by 25.5% to 32.8%. We identified novel and validated previously known associations of DNA methylation with 3 subtypes of atherosclerosis. Results suggest that in blood, the epigenetic signature of atherosclerosis largely reflects cumulative exposure, particularly smoking and cardiometabolic dysregulation, rather than strongly distinguishing vasculature-specific biological processes.

Low resting ankle-brachial index (ABI) is a marker of poor cardiovascular outcomes. Whether modest decrements in ABI translate into higher risks of major adverse limb events (MALE) is unclear because prior studies are small or lack racial diversity and incident outcomes. The purpose of this study was to assess the association between the full range of ABI measures and incident MALE in a large, diverse cohort. Using data from the Veterans Aging Cohort Study-National Cohort, we analyzed a prospective, longitudinal cohort of veterans free of prevalent peripheral artery disease (PAD). Participants were enrolled beginning January 1, 2000, and followed through September 30, 2021. The exposure was resting ABI (continuous and categorical), and the primary outcome was MALE, defined as amputation or revascularization using administrative codes. Secondary outcomes included total amputation, major amputation, or revascularization. Cox proportional hazards models assessed the overall association between ABI and MALE and stratified by sex or race. Models were adjusted for demographics and PAD risk factors. The analysis included 223,350 people, including 8,207 women and 42,173 Black individuals. There were 28,191 MALE. Risk of MALE followed an inverse j-shaped distribution across the continuous ABI spectrum. Compared with a categorical ABI of 1.11 to 1.20, borderline ABI values (range 0.91-1.00) were associated with an increased risk of MALE in the total population as well as sex/race subgroups: total population: HR: 1.53 (95% CI: 1.43-1.64); men: HR: 1.53 (95% CI: 1.43-1.64); women: HR: 2.00 (95% CI: 1.18-3.38); White individuals: HR: 1.60 (95% CI: 1.48-1.73); Black individuals: HR: 1.39 (95% CI: 1.18-1.64). Similar associations were demonstrated for major amputation (HR: 1.34 [95% CI: 1.17-1.54]), total amputation (HR: 1.22 [95% CI: 1.12-1.33]), and revascularization (HR: 2.05 [95% CI: 1.87-2.26]) in the full cohort. ABI was a stronger marker of MALE risk than established risk factors, including current smoking and prevalent cardiovascular disease. In a large, diverse cohort free of prior PAD, ABI values across the full spectrum were associated with an increased risk of incident MALE, suggesting that treating the ABI as a binary measure does not adequately capture clinical risk. Further studies are needed to better understand why MALE occurs despite near-normal ABI values.

Transcatheter aortic valve replacement (TAVR) is an established alternative to surgical aortic valve replacement for symptomatic severe aortic stenosis, but long-term, comparative clinical outcomes and echocardiography data are lacking. Our goal was to compare 10-year clinical and echocardiographic outcomes after balloon-expandable TAVR or surgery in intermediate-risk surgical patients in the PARTNER 2A randomized trial. Between 2011 and 2013, patients with severe, symptomatic aortic stenosis at intermediate surgical risk were randomized at 57 centers to TAVR with the balloon-expandable SAPIEN XT system (Edwards Lifesciences) or to surgery. Randomization was stratified by anatomical suitability for transfemoral (TF) or transthoracic (transapical/transaortic [TA/TAo]) access. Ten-year outcomes were evaluated in the valve implant population and included all-cause mortality, aortic valve reintervention, and core laboratory-adjudicated echocardiographic outcomes. To obtain 10-year data, patient reconsent at 5 years was required, and vital status sweeps were implemented to improve data completeness for all-cause mortality. Among 1,910 randomized patients who received a valve, 974 underwent TAVR (TF: 749/974 [76.9%]) and 936 had surgery. Mean patient age was 81.6 years, 45.4% were women, and the mean Society of Thoracic Surgeons score was 5.8%. At 10 years, vital status was available for 881 of 974 patients (90.5%) and 838 of 936 patients (89.5%). All-cause 10-year mortality with vital status sweeps was 86.1% after TAVR and 82.8% after surgery (HR: 1.13; 95% CI: 1.02-1.25; P = 0.02). When stratified by access route, rates of all-cause mortality for TAVR and surgery in the TF group were similar (83.9% vs 82.1%, respectively; P = 0.27), whereas mortality was higher for TAVR in the TA/TAo group (93.2% vs 85.1%; P < 0.01; P for interaction = 0.03). Cumulative incidence rates of aortic valve reintervention at 10 years were 6.3% for TAVR and 1.6% for surgery (P < 0.001). Of the 24 TAVR and 35 surgical patients with available echocardiographic data at 10 years, mean gradients were 12.6 mm Hg and 12.7 mm Hg, respectively. At the 10-year follow-up, TAVR in intermediate-risk patients with the SAPIEN XT prosthesis compared with surgery was associated with lower survival rates, with differences predominantly observed in the TA/TAo access cohort. TAVR with the XT valve was also associated with significantly higher rates of aortic valve reintervention. (PARTNER II Trial: Placement of AoRTic TraNscathetER Valves II - XT Intermediate and High Risk [PII A]; NCT01314313).

Inclisiran is a small interfering ribonucleic acid targeting hepatic proprotein convertase subtilisin/kexin type 9 messenger RNA, that effectively reduces low-density lipoprotein cholesterol (LDL-C) levels. The effect of inclisiran on cardiovascular (CV) outcomes has not been formally tested. VICTORION-2 Prevent (NCT05030428) is an ongoing, Phase 3 randomized, double-blind, placebo-controlled, international trial assessing the efficacy and safety of inclisiran in preventing CV events in patients with established atherosclerotic cardiovascular disease (ASCVD) receiving high-intensity statin therapy. Patients with established ASCVD (history of myocardial infarction [MI], ischemic stroke, or symptomatic peripheral artery disease), and fasting plasma LDL-C &#x2265;1.8 mmol/L (70 mg/dL) despite high-intensity statin therapy (&#x2265;20 mg rosuvastatin or &#x2265;40 mg atorvastatin daily) will be enrolled. Patients will be treated with inclisiran sodium 300 mg or placebo, administered subcutaneously at Day 1, Day 90, and every 6 months thereafter. The primary outcome will include time to first occurrence of 3-point major adverse CV events (3P-MACE; composite of CV death, MI, or ischemic stroke). Secondary outcomes will include time to occurrence of CV death, time to first occurrence of 4P-MACE (composite of 3P-MACE and urgent revascularization), and major adverse limb event (all adjudicated outcomes), time to occurrence of all-cause death, and long-term safety of inclisiran. Safety will be monitored using a selective safety data collection strategy. VICTORION-2 Prevent will provide robust data on CV benefits and safety of inclisiran in patients with established ASCVD and not at guideline-recommended LDL-C goals despite high-intensity statin treatment.

Interleukin (IL)-6 has emerged as a promising target for cardiovascular disease (CVD) prevention. Better understanding IL-6's contribution to CVD events in community-based, diverse cohorts and in clinically relevant subgroups will provide critical context about IL-6 inhibition for CVD prevention. The aim of this study was to evaluate the association of circulating IL-6 concentrations with incident cardiovascular events and mortality using pooled data from large multiethnic prospective cohorts. The authors harmonized individual-level participant data from 14 cohorts with blood IL-6 measurements and follow-up data on any of 9 prespecified outcomes: myocardial infarction, stroke, atrial fibrillation, heart failure, total coronary heart disease (CHD), total CVD, all-cause mortality, CVD-specific mortality, and CHD-specific mortality. Multivariable-adjusted Cox proportional hazards models were used to estimate HRs and corresponding 95% CIs. IL-6 was analyzed by quartiles and as a log-transformed continuous variable. Associations were further examined by chronic kidney disease status, diabetes status, high-sensitivity C-reactive protein (hsCRP) concentrations, body mass index categories, as well as in secondary prevention. Discrimination was evaluated using the area under the curve across 4 models: base, base plus IL-6, base plus hsCRP, and base plus both markers. Among 59,396 participants, the median IL-6 concentration was 1.91 pg/mL. The mean age was 63.6 &#xb1; 12.4 years. 67.6% were women, and 20.6% were Black. The longest median follow-up time was 15.8 years (for CVD-specific mortality). Higher IL-6 concentrations were associated with increased risk for all 9 outcomes. The strongest association was observed for CHD-specific mortality, with an adjusted HR of 2.12 (95% CI: 1.88-2.39) in the highest compared with the lowest IL-6 quartile. The weakest association was for myocardial infarction (HR: 1.45; 95% CI: 1.28-1.64). Findings were robust and consistent in all key subgroups as well as in secondary prevention. IL-6 alone demonstrated modest additive discrimination beyond hsCRP for stroke, heart failure, CVD, CHD, and mortality. In this large, harmonized, individual-level participant data analysis of prospective cohorts, higher IL-6 concentrations were strongly associated with 9 cardiovascular and mortality outcomes after controlling for clinical covariates. These associations were consistent across cardiometabolic subgroups, chronic kidney disease status, and secondary prevention populations, highlighting the broad and consistent role of IL-6-mediated inflammation in cardiovascular risk.

Transcatheter aortic valve replacement (TAVR) is an alternative to surgical aortic valve replacement for patients with symptomatic severe aortic stenosis. However, long-term outcomes data are lacking for TAVR, particularly with newer-generation transcatheter heart valves. The purpose of this study was to compare 10-year outcomes of intermediate-risk patients who underwent TAVR with the third-generation, balloon-expandable SAPIEN 3 valve in the PARTNER 2 SAPIEN 3 Intermediate-risk Registry (P2S3i) with those who underwent surgery in the PARTNER 2A (P2A) randomized trial. Intermediate-risk patients were enrolled in the P2A trial from 2011 through 2013 and in the P2S3i registry in 2014. These prospective, multicenter studies used the same eligibility criteria and stratified patients based on suitability for transfemoral or transthoracic (transapical/transaortic) access. Ten-year outcomes were evaluated, including all-cause mortality, aortic valve reintervention, and core laboratory-adjudicated echocardiographic outcomes. Patient reconsent was required at 5 years for extended 10-year follow-up, and vital status sweeps were implemented to improve data completeness for all-cause mortality. To account for potential baseline differences and reduce confounding, P2S3i TAVR patients were propensity score-matched 1:1 to P2A surgical patients. Among 2,005 patients who received a valve, 1,069 underwent TAVR in P2S3i and 936 underwent surgery in P2A. After propensity score matching (N = 783 patients in each group), baseline characteristics were similar between groups: mean age was approximately 82 years, 43% were female, and mean Society of Thoracic Surgeons score was 5.5%. At 10 years, all-cause mortality rate was 83.4% after TAVR and 82.3% after surgery, respectively (HR: 1.01 [95% CI: 0.91-1.13]; P = 0.82). Aortic valve reintervention rates adjusted for competing mortality were 2.0% for TAVR and 1.9% for surgery (P = 0.47). Among 32 TAVR and 30 surgical patients with available echocardiographic data at 10 years, mean gradients were 11.0 mm Hg and 12.6 mm Hg, respectively. At 10 years, TAVR with the SAPIEN 3 valve and surgery resulted in similar rates of mortality and aortic valve reintervention, and similar hemodynamics in intermediate-risk patients with symptomatic severe aortic stenosis. This analysis highlights challenges associated with extended long-term follow-up of clinical trials, including differential loss to follow-up and the competing risk of mortality in elderly populations. (PARTNER 2A Trial; NCT01314313; PARTNER 2 SAPIEN 3 Intermediate-Risk Registry; NCT03222128).

Long-term resistance training may influence cardiovascular health, but evidence in women, particularly in the context of aerobic activity and sedentary behavior, remains limited. This study sought to examine the association between long-term resistance training and risk of major cardiovascular disease (CVD) in women, and to evaluate joint associations with aerobic activity, sedentary television viewing, and key training-related characteristics. We conducted a prospective cohort study among 117,025 women from the Nurses' Health Study (N = 45,669; 2002-2020) and Nurses' Health Study II (N = 71,356; 2003-2017), with up to 5 repeated assessments of physical activity. Resistance training was reported every 4 years, and time-varying cumulative averages were calculated to represent long-term exposure. The primary outcome was incident major CVD, defined as nonfatal or fatal myocardial infarction (MI), stroke, coronary artery bypass grafting, or percutaneous coronary intervention. Over a mean of 14.5 years of follow-up (1,630,964 person-years), 5,459 incident major CVD events occurred. Compared with no resistance training, women performing &#x2265;2 h/wk had a 20% lower risk of major CVD (HR: 0.80; 95% CI: 0.69-0.92; P for trend = 0.007), and each additional 1 h/wk was associated with a 5% lower risk (HR per 1 h/wk: 0.95; 95% CI: 0.92-0.99). The inverse association was stronger for MI (HR for &#x2265;2 h/wk vs none: 0.56; 95% CI: 0.41-0.76) but not evident for stroke (HR: 0.99; 95% CI: 0.80-1.23). Women who met recommendations for aerobic activity (&#x2265;15 metabolic equivalent of task hours per week), resistance training (&#x2265;1 h/wk), and low sedentary television viewing (<2 h/d) had a lower risk of major CVD (HR: 0.60; 95% CI: 0.53-0.69), than those meeting aerobic and low sedentary television viewing recommendations but not resistance training (HR: 0.73; 95% CI: 0.67-0.80). Greater consistency in maintaining resistance training (&#x2265;75% of follow-up) and engaging in both upper and lower limb training were associated with stronger inverse associations. In this large prospective study of U.S. women, consistent resistance training, especially when integrated with recommended levels of aerobic activity and reduced sedentary television viewing, was associated with a substantially lower risk of major CVD, particularly MI.

Cardiovascular-kidney-metabolic (CKM) syndrome highlights the inter-related nature of cardiometabolic risk factors, kidney disease, and cardiovascular disease (CVD) and represents an important target for intervention amid rising cardiovascular mortality in the United States. However, contemporary treatment patterns of major cardiometabolic risk factors in this high-risk population are not well defined. The purpose of this study was to characterize national treatment rates of hypertension, diabetes, and hyperlipidemia among U.S. adults with CKM syndrome and to assess risk factor control among treated individuals from 2015 through 2023. We analyzed data from adults aged &#x2265;20 years with CKM stage 2 and above who participated in the National Health and Nutrition Examination Survey from 2015 through August 2023. Treatment rates for hypertension, diabetes, and hyperlipidemia and rates of blood pressure, glycemic, and cholesterol control among treated individuals were estimated using age- and sex-adjusted analyses that accounted for the complex survey design. The study included 6,384 adults with CKM stage 2 and above (weighted mean age 44.2 years; 51.2% women). Only approximately one-half of adults with hypertension (51.3% [95% CI: 49.7%-52.8%]) or hyperlipidemia (48.8% [95% CI: 46.7%-51.0%]) were receiving treatment, while diabetes treatment rates were higher (83.4% [95% CI: 80.1%-86.6%]). Among treated individuals, blood pressure control was achieved in 44.7% (95% CI: 41.6%-47.7%), glycemic control in 47.3% (95% CI: 42.7%-51.8%), and cholesterol control in 68.2% (95% CI: 65.2%-71.1%). Treatment rates for hypertension and hyperlipidemia increased across higher risk strata, while blood pressure and glycemic control were lower among treated adults with higher 10-year CVD risk. Adults aged 20-44 years consistently had the lowest treatment rates across all 3 conditions (hypertension 27.6% [95% CI: 24.8%-30.3%], diabetes 73.7% [95% CI: 63.8%-83.7%], hyperlipidemia 19.7% [95% CI: 15.2%-24.3%]), while women were less likely than men to receive treatment for diabetes and hyperlipidemia. Among racial and ethnic subgroups, Hispanic adults had the lowest treatment rates for hypertension and hyperlipidemia. Among U.S. adults with CKM syndrome, treatment of hypertension and hyperlipidemia was low, and fewer than one-half of treated individuals achieved blood pressure or glycemic control. Gaps in treatment initiation were most pronounced among young adults, women, and Hispanic adults, and inadequate risk factor control was particularly evident among those with higher cardiovascular risk. These findings highlight substantial opportunities to improve cardiometabolic care in this high-risk population.

Tirzepatide is a once-weekly glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist approved for treatment of type 2 diabetes and obesity. The effect of tirzepatide on cardiovascular risk biomarkers in people with overweight or obesity remains uncertain. The purpose of this study was to evaluate the association of tirzepatide compared to placebo on biomarkers that reflect inflammation (high-sensitivity C-reactive protein, interleukin-6, fibrinogen, leukocytes), metabolic/adiposity/hepatic stress (homeostatic model assessment of insulin resistance, leptin, gamma-glutamyl transferase, fibroblast growth factor-21, adiponectin, free fatty acids), endothelial dysfunction (soluble intercellular adhesion molecule-1, E-selectin), and hemostasis/thrombosis (plasminogen activator inhibitor-1:antigen [Ag], tissue plasminogen activator:Ag, thrombomodulin, platelets) in people with obesity. The aforementioned biomarkers were assayed from plasma samples, collected at baseline, 24 weeks, and 72 weeks, from 100 randomly selected participants from each group of the SURMOUNT-1 trial who completed treatment with once-weekly placebo or tirzepatide 5, 10, or 15 mg (n = 392 after low sample volumes excluded). The change in each log-transformed biomarker level over time was evaluated by a mixed model for repeated measures, with change at 72 weeks the primary outcome of interest. Model estimates were back-transformed to the original (geometric mean ratio) scale and expressed as percent change in geometric means. Pearson correlations between log change in biomarker levels and weight were done on pooled tirzepatide doses. At week 72, tirzepatide was associated with significantly greater reductions (negative values) or increases (positive values) in biomarker geometric means compared with placebo. For the 5-, 10-, or 15-mg doses, respectively, these included high-sensitivity C-reactive protein (-36.9%, -46.9%, -54.6%), interleukin-6 (-25.4%, -27.8%, -30.2%), leukocytes (not significant [NS], -8.6%, -10.0%), homeostatic model assessment of insulin resistance (-26.4%, -35.5%, -39.1%), leptin (-44.4%, -59.3%, -61.4%), gamma-glutamyl transferase (-18.6%, -21.6%, -32.7%), fibroblast growth factor-21 (-27.4%, -27.6%, -39.9%), adiponectin (21.1%, 35.1%, 47.7%), free fatty acids (NS, NS, -17.1%), soluble intercellular adhesion molecule-1 (NS, -9.7%, -11.1%), E-selectin (-12.6%, -20.0%, -26.4%), plasminogen activator inhibitor-1:Ag (-41.4%, -35.6%, -44.3%), and platelets (NS, NS, -6.0%) (all adjusted P < 0.05). No consistent associations were observed between tirzepatide and changes in fibrinogen, tissue plasminogen activator:Ag, or thrombomodulin. In this post hoc analysis, tirzepatide was associated with improvements in biomarkers of metabolic/adiposity/hepatic stress and endothelial dysfunction, as well as selected biomarkers of inflammation and hemostasis/thrombosis. This analysis provides a comprehensive, long-term, randomized assessment of biomarker changes across multiple cardiovascular pathways during tirzepatide treatment in obesity. (A Study of Tirzepatide [LY3298176] in Participants With Obesity or Overweight [SURMOUNT-1]; NCT04184622).

Cardiac amyloidosis (CA) is a progressive infiltrative cardiomyopathy associated with conduction disease and arrhythmias, although their true burden and relationship with disease phenotype remain incompletely defined. The purpose of this study was to prospectively characterize arrhythmic burden using implantable loop recorders and explore associations with amyloid subtype and disease characteristics. In this prospective single-center observational study, 110 treatment-na&#xef;ve patients with a new diagnosis of transthyretin amyloid cardiomyopathy (ATTR-CM) or light-chain cardiac amyloidosis (AL-CA) underwent comprehensive phenotyping, including cardiac magnetic resonance, followed by implantable loop recorder implantation. Among 110 patients (ATTRwt-CM: 43, ATTRv-CM: 20, AL-CA: 47) bradyarrhythmias with a Class I indication for pacemaker implantation occurred in 17.3% and were more frequent in ATTR-CM than AL-CA (15 [23.8%] vs 4 [8.5%]; P = 0.036). Baseline conduction abnormalities (QRS duration: sHR: 1.03; [95% CI: 1.01-1.04]; P < 0.001) and higher myocardial amyloid burden were associated with subsequent bradyarrhythmic events (ECV: sHR: 1.06 [95% CI: 1.02-1.10]; P = 0.002). New atrial fibrillation occurred in 28.2% of patients without prior atrial fibrillation and was more frequent in ATTR-CM than AL-CA (15 [50.0%] vs 5 [12.2%]; P < 0.001) with higher amyloid burden associated with increased risk (ECV: sHR: 1.04; 95% CI: 1.00-1.08; P = 0.038). During follow-up 21 (19.1%) patients died (ATTR-CM: 10 [15.9%]; AL-CA: 11[23.4%]). In patients with ATTR-CM, the terminal cardiac rhythm was uniformly pulseless electrical activity; in patients with AL-CA, PEA was the terminal rhythm in 9 (81.8%) patients and 2 (18.2%) had sustained ventricular arrhythmias. In CA, clinically significant arrhythmias are common and frequently asymptomatic. Arrhythmic burden and patterns differ between amyloid subtypes and are closely associated with disease phenotype and myocardial amyloid burden. These findings provide prospective insights into arrhythmogenesis in CA and support the need for further studies to refine risk stratification and inform management strategies. (Exploration of Arrhythmia Burden in Cardiac Amyloidosis Using Implantable Loop Recorders [EXCALIBUR]; NCT04856267).

The multicenter, randomized, sham-controlled FAVOR III China trial (Comparison of Quantitative Flow Ratio-Guided and Angiography-Guided Percutaneous Intervention in Patients with Coronary Artery Disease) demonstrated that quantitative flow ratio (QFR)-guided percutaneous coronary intervention (PCI) resulted in better outcomes compared with angiographic guidance at 1-year and 2-year follow-up. Whether these benefits are sustained over long-term follow-up remains uncertain. The purpose of this study was to evaluate the long-term effectiveness and safety of a QFR-guided PCI strategy compared with angiography-guided PCI at 5 years. Patients with at least 1 angiographically intermediate coronary lesion (50%-90% diameter stenosis) in a vessel &#x2265;2.5 mm diameter were randomized to a QFR-guided (PCI performed only if QFR &#x2264;0.80) or angiography-guided strategy. The primary endpoint was major adverse cardiac events (a composite of all-cause death, myocardial infarction, or ischemia-driven revascularization) at 1 year; 5-year outcomes data are reported herein. At 5 years, major adverse cardiac events composite was lower with QFR guidance than with angiography guidance (17.5% vs 21.1%; HR: 0.80; 95% CI: 0.69-0.92; P = 0.002), driven by fewer myocardial infarctions (5.8% vs 9.0%; HR: 0.63; 95% CI: 0.49-0.80; P < 0.0001) and ischemia-driven revascularizations (9.6% vs 12.0%; HR: 0.78; 95% CI: 0.64-0.95; P = 0.02) in the QFR-guided group. All-cause death did not differ between groups. Landmark analysis showed that the benefit of QFR guidance accrued predominantly within the first 2 years (8.5% vs 12.5%; HR: 0.66; 95% CI: 0.54-0.81; P < 0.0001), with similar outcomes between 2 and 5 years (10.2% vs 11.2%; HR: 0.90; 95% CI: 0.73-1.11; P = 0.32; P for interaction = 0.001). Compared with angiography guidance, QFR-guided strategy improved 5-year clinical outcomes, with benefits primarily achieved within the first 2 years. (The FAVOR III China Study; NCT03656848).

Early identification of worsening heart failure (HF) may improve outcomes. This study aims to assess if insertable cardiac monitor (ICM)-based high-risk detection combined with centrally managed, nurse-facilitated, individually protocolized diuretic interventions is safe and improves HF outcomes. A Reveal LINQ (Medtronic) ICM with an investigational HF risk-status software was implanted in participants with HF who were randomized 1:1 to an intervention arm (high-risk HF alert triggering protocolized diuretic regimen) or an observation arm (standard care). The primary safety endpoint was intervention-related serious adverse events and the primary efficacy endpoint was a 5-component hierarchical composite including cardiovascular death or HF hospitalization or outpatient HF event within 60 days of high-risk onset, Kansas City Cardiomyopathy Questionnaire Clinical Summary Score, and 6-minute walk distance, analyzed using win ratio. A total of 711 participants were randomized (357 intervention, 354 observation). The primary composite endpoint did not significantly differ between groups (win ratio: 0.79; 95% CI: 0.62-1.01; P = 0.06). Over a mean follow-up of 17.3 &#xb1; 8.9 months, the serious adverse events rate was 0.32% (95% CI: 0.10%-0.99%; prespecified safety threshold &#x2264;5%). The cumulative cardiovascular death and HF events were numerically higher in the intervention group (HR: 1.43; 95% CI: 0.95-2.15; P = 0.091). In an exploratory sensitivity analysis adjusting for a baseline Kansas City Cardiomyopathy Questionnaire imbalance, the win ratio was 1.02 (95% CI: 0.80-1.31; P = 0.85). ICM-based risk status detection with centrally coordinated diuretic intervention was safe and yielded a neutral result for the primary composite outcome under the tested implementation strategy (ALLEVIATE-HF [Algorithm Using LINQ Sensors for Evaluation and Treatment of Heart Failure]; NCT04452149).