Kaul U, Sinha SK, Singh R
… +29 more, Parida AK, Mody R, Abhaichand R, Banker D, Khan A, Kalyansundaram A, Moorthy N, Sharma R, Chandra S, Bordoloi N, Kumar D, Chandra Koduganti S, Gunasekaran S, Kapoor R, Baruah R, Mantri RR, Patil R, Sharma Y, Agrawal DK, Ragava PV, Garg R, Reddy KMK, Chandra P, Kumar S, Arambam P, Khan N, Sudhir K, Bangalore S, TUXEDO- 2 India Investigators
J Am Coll Cardiol
· 2026 Jun · PMID 42383943
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BACKGROUND: Patients with diabetes frequently have multivessel disease and are at increased risk of adverse outcomes. The outcomes with a new-generation ultra-thin strut sirolimus-eluting stent (SES) vs everolimus-elutin...BACKGROUND: Patients with diabetes frequently have multivessel disease and are at increased risk of adverse outcomes. The outcomes with a new-generation ultra-thin strut sirolimus-eluting stent (SES) vs everolimus-eluting stent (EES) is unclear as stent-to-stent comparison trials have routinely excluded these patients or included a small proportion of such patients. OBJECTIVES: The purpose of this study was to compare the clinical outcomes of ultra-thin biodegradable polymer (BP) SES vs durable polymer (DP) EES when combined with contemporary optimal medical therapy in patients with diabetes and multivessel disease. METHODS: The TUXEDO-2 is an investigator-initiated prospective, open-label, multicenter, 2 × 2 factorial, randomized (1:1) controlled trial. Patients undergoing percutaneous coronary intervention were randomized to receive either a Supraflex Cruz SES or Xience EES. The participants were also randomized to Ticagrelor or Prasugrel. The primary endpoint was target lesion failure, a composite of cardiac death, target vessel myocardial infarction or ischemia-driven target lesion revascularization at 1-year follow up. The trial was designed to test noninferiority of BP-SES vs DP-EES, with a noninferiority margin of 4.5% (1-sided upper 97.5% confidence bound). RESULTS: Among the 1,800 patients randomized, mean age was 60.3 years with 28% of participants being women. At 1 year, the primary endpoint of target lesion failure occurred in 148 patients, including 70 patients (7.92%) in the BP-SES group and 78 patients (8.75%) in the DP-EES group. The risk difference of -0.83 percentage points (1-sided upper 97.5% confidence bound 3.42%) met the prespecified noninferiority margin (P = 0.005). There were no significant differences in cardiac death (3.6% vs 3.4%), target vessel myocardial infarction (6.61% vs 7.54%), and ischemia-driven target lesion revascularization (0.8% vs 1.0%) between the 2 groups. Nonfatal myocardial infarction (4.7% vs 6.4%) and stent thrombosis was similar (1.0 % vs 0.7%) between the 2 groups. CONCLUSIONS: In patients with diabetes and multivessel disease undergoing percutaneous coronary intervention, ultra-thin biodegradable polymer SES was noninferior to durable polymer EES at 1 year follow-up. (Trial Registration Number CTRI/2019/11/022088).
Sanghvi MM, Nicholls HL, Kaplan TM
… +13 more, Chadalavada S, Ramírez J, Stokes T, Lim C, Mcleod JC, Phillips SM, Phillips BE, Atherton PJ, Khanji MY, Petersen SE, Timmons JA, Munroe PB, Aung N
J Am Coll Cardiol
· 2026 Jun · PMID 42383941
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BACKGROUND: The prognostic value of obesity in cardiovascular disease is complex. Measures such as body mass index and waist-to-height ratio show differing associations with outcomes, especially in heart failure. Assessi...BACKGROUND: The prognostic value of obesity in cardiovascular disease is complex. Measures such as body mass index and waist-to-height ratio show differing associations with outcomes, especially in heart failure. Assessing sarcopenic obesity, the coexistence of excess fat and low muscle mass, may clarify this relationship; however, quantifying sarcopenia in clinical practice remains challenging. OBJECTIVES: The goal was to establish a translatable method of assessing sarcopenic obesity from cardiovascular imaging and assess its clinical relevance using long-term follow-up, genomic, and transcriptomic data. METHODS: We developed a deep learning pipeline to quantify pectoralis major muscle mass from 55,768 cardiovascular magnetic resonance examinations and combined this with body weight to derive a novel sarcopenic obesity index. Associations with cardiac remodeling phenotypes and adverse cardiovascular and mortality outcomes were tested in multivariable models. Genome-wide association analysis, colocalization, and polygenic risk score evaluation were performed for the sarcopenic obesity index. Transcriptomic profiling of skeletal muscle across 7 pathophysiological states assessed differential gene expression. RESULTS: A higher sarcopenic obesity index was associated with adverse cardiac remodeling, and with increased risk of incident heart failure (HR: 1.31; 95% CI: 1.16-1.49), cardiovascular death (HR: 1.51; 95% CI: 1.25-1.81), and all-cause mortality (HR: 1.37; 95% CI: 1.26-1.49). Genome-wide association analysis identified 16 loci for sarcopenic obesity. Loci included genes associated with heart failure and nonischemic cardiomyopathy, with colocalization implicating shared causal variants in heart failure. Transcriptomic profiling demonstrated that sarcopenic obesity loci were specifically modulated during muscle atrophy. Analyses identified ACVR2B, the target of bimagrumab, which is being tested with semaglutide to enhance fat loss while maintaining lean mass. CONCLUSIONS: These results establish sarcopenic obesity as a clinically meaningful cardiovascular risk phenotype and point to viable therapeutic targets.
Kumbhani DJ, Gibson CM, Kinlay S
… +4 more, Peterson ED, Pollak AW, Tamis-Holland JE, Verheugt FWA
J Am Coll Cardiol
· 2026 Jun · PMID 42377293
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Antiplatelet medications have been fundamental to the management of atherosclerotic cardiovascular disease (ASCVD); however, recommendations for their use have evolved over the past decade. Aspirin remains the most widel...Antiplatelet medications have been fundamental to the management of atherosclerotic cardiovascular disease (ASCVD); however, recommendations for their use have evolved over the past decade. Aspirin remains the most widely used antiplatelet drug. Recent data do not support a benefit for primary prevention of ASCVD in unselected populations with routine aspirin use; consideration should be reserved for those at highest ischemic risk. Similarly, the evolution of drug-eluting stents, antiplatelet medications, and research on the optimal regimen and duration of dual antiplatelet therapy have altered evidence-based recommendations for use of antiplatelets in managing patients diagnosed with ASCVD. Antiplatelet medications remain powerful tools to prevent ischemic events, particularly for those who have experienced an acute coronary syndrome, but the balance between the risk of ischemia and the risk of bleeding poses a perpetual challenge and requires individualized treatment. This scientific statement provides a detailed overview of current evidence for the use of antiplatelets in the management of ASCVD. This includes a comparison of current clinical practice guideline-based recommendations, summary of pivotal trials, and discussion of antiplatelet use in patients with elevated bleeding risk or those undergoing surgery. Considerations for use of antiplatelets in those with different phenotypes of ASCVD and those with indications for concurrent use of antithrombotic medications, as well as long-term monitoring and adherence, are addressed.
Kumbhani DJ, Armbruster AL, Cheng RK
… +5 more, Chrispin J, Fischer U, Holbrook AM, Joglar J, Sevestre MA
J Am Coll Cardiol
· 2026 Jun · PMID 42377292
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Direct oral anticoagulants (DOACs) have transformed the prevention and treatment of thromboembolic disease, offering predictable pharmacokinetics, fewer interactions, and improved safety compared with vitamin K antagonis...Direct oral anticoagulants (DOACs) have transformed the prevention and treatment of thromboembolic disease, offering predictable pharmacokinetics, fewer interactions, and improved safety compared with vitamin K antagonists. Over the past decade, DOACs have become the preferred oral anticoagulants for most patients with atrial fibrillation and venous thromboembolism; yet, important gaps remain in their optimal implementation across diverse clinical scenarios. Despite strong evidence supporting their efficacy and safety, DOACs continue to be underutilized and sometimes inappropriately dosed, particularly among patients at elevated thrombotic risk and in populations historically underrepresented in randomized trials. This American College of Cardiology Scientific Statement provides a comprehensive, evidence-based overview of established and emerging indications for DOAC therapy in primary and secondary prevention of thrombotic events. Key domains include anticoagulation in atrial fibrillation, acute and extended treatment of venous thromboembolism, management in special populations (including patients with chronic kidney disease, liver dysfunction, cancer, obesity, frailty, prior bleeding, and valvular heart disease), periprocedural anticoagulation, and antithrombotic strategies following stroke, left atrial appendage closure, and catheter ablation. The document also addresses practical considerations such as drug selection, dosing strategies, duration of therapy, bleeding risk assessment, management of anticoagulant-related bleeding, drug-drug interactions, adherence, and cost-related barriers to care. This statement is intended to complement existing clinical practice guidelines by synthesizing evolving data, clarifying areas of uncertainty, and supporting individualized, patient-centered decision making. By addressing both evidence and implementation challenges, this document aims to improve the appropriate and equitable use of DOACs across the spectrum of thrombotic disease.
Walsh MN, Kober L, Sliwa K
… +21 more, Adamo M, Agarwal A, Banerjee A, Bozkurt B, Cikes M, Damasceno A, Desai AS, Felker GM, Hogan G, Kinugawa K, Kittleson M, Lam CSP, McDonagh T, Metra M, Mullens W, Ribeiro ALP, Vaughn Y, Vest A, Joint American Heart Association (AHA)/American College of Cardiology (ACC)/European Society of Cardiology (ESC)/World Heart Federation (WHF), Task Force for the Universal Definition of Heart Failure in collaboration with the Heart Failure Society of America (HFSA), Heart Failure Association (HFA) of the European Society of Cardiology, and the Japanese Heart Failure Society (JHFS)
J Am Coll Cardiol
· 2026 Jun · PMID 42370864
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Heart failure (HF) remains a pressing health concern, with rising prevalence globally. Subjectivity and ambiguity in the definition of HF and its antecedent stages have limited research, global surveillance, and preventi...Heart failure (HF) remains a pressing health concern, with rising prevalence globally. Subjectivity and ambiguity in the definition of HF and its antecedent stages have limited research, global surveillance, and prevention programs. To address this, several cardiac societies and foundations convened to standardize the definition of HF in 2021 and designated stage B or pre-HF to identify individuals at risk of developing HF. In subsequent years, substantial progress and changes have been made in aspects of preventing HF, improving HF diagnosis and management, and recognizing the importance of the affected individual's voice. Global differences and disparities in HF are better understood, as are causes and comorbidities leading to differences in care, which are also influenced by access to care. This consensus document presents the Second Universal Definition of Heart Failure, aiming to standardize terminology and facilitate a uniform approach for clinicians, researchers, health systems, and policymakers. In this definition, the classification of HF phenotypes moves away from rigid left ventricular ejection fraction cutoffs, instead grouping HF into reduced, preserved, and improved ejection fraction categories to better reflect clinical realities. A universal classification of HF causes is also proposed. The document also addresses the dynamic trajectories of HF-improvement, remission, and recovery-and highlights the impact of social determinants and geographic variation on HF risk and outcomes. By providing a comprehensive, standardized framework for HF definition and classification, this document seeks to improve prevention, early detection, and management of HF worldwide, ultimately enhancing patient care and advancing global cardiovascular health.
Soukoulis V, Afari ME, Abideen Asad ZUL
… +5 more, Banerjee D, Singh A, Subramanyam P, Freed BH, American College of Cardiology Program Director and Graduate Medical Education Council
J Am Coll Cardiol
· 2026 Jun · PMID 42367157
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Annink ME, Beverloo CYY, Kraaijenhof JM
… +5 more, Reeskamp LF, Galenkamp H, van den Born BH, Stroes ESG, Nurmohamed NS
J Am Coll Cardiol
· 2026 Jun · PMID 42340290
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BACKGROUND: Low-density lipoprotein cholesterol (LDL-C), lipoprotein(a) (Lp[a]), and high-sensitivity C-reactive protein (hsCRP) capture different pathways driving atherosclerotic cardiovascular disease (ASCVD). However,...BACKGROUND: Low-density lipoprotein cholesterol (LDL-C), lipoprotein(a) (Lp[a]), and high-sensitivity C-reactive protein (hsCRP) capture different pathways driving atherosclerotic cardiovascular disease (ASCVD). However, it is unknown whether their combined assessment provides reliable risk stratification in different ethnic populations with markedly different distributions of these biomarkers as well as background risk of ASCVD. OBJECTIVES: The goal was to evaluate independent and joint associations of LDL-C, Lp(a), and hsCRP with incident ASCVD and to formally assess additive and multiplicative interaction of these biomarkers in a multiethnic cohort, and to determine whether these associations are consistent across participants of African, European, and South Asian Surinamese descent. METHODS: Among 15,676 HELIUS (HEalthy Life In an Urban Setting) participants without prior myocardial infarction or ischemic stroke (mean age 44.4 ± 13.2 years; 56.0% women), incident ASCVD was identified through linkage to nationwide registries. Fine-Gray competing-risk models were used to assess associations across increasing biomarker quintiles and joint elevations. Additive interaction was assessed using the relative excess risk due to interaction, attributable proportion, and synergy index. Incremental predictive value of Lp(a) and hsCRP beyond a PREVENT-ASCVD (Predicting Risk of Cardiovascular Disease EVENTs-Atherosclerotic Cardiovascular Disease)-based clinical model was evaluated using time-dependent area under the curve and continuous net reclassification improvement. RESULTS: Over median 8.9-year follow-up (138,375 person-years), 378 ASCVD events occurred. Top vs bottom quintile adjusted subdistribution HRs were 1.39 (95% CI: 1.09-1.79) for LDL-C, 1.86 (95% CI: 1.54-2.25) for Lp(a), and 1.51 (95% CI: 1.34-1.71) for hsCRP. Formal interaction assessment showed no interaction on either the multiplicative or additive scale. Risk increased with the number of elevated biomarkers, reaching a 2.44-fold increase (95% CI: 1.46-4.09) among those with all 3 elevated. Consistent dose-response patterns were observed across ethnic groups (P = 0.75), although absolute ASCVD risk was approximately 3-fold higher in South Asian Surinamese participants. Addition of Lp(a) and hsCRP to a clinical model modestly improved discrimination at 10 years (Δ area under the curve: 0.006; P = 0.030) and reclassification (continuous net reclassification improvement: 0.165; 95% CI: 0.050-0.289). CONCLUSIONS: In a multiethnic primary prevention cohort, combined assessment of LDL-C, Lp(a), and hsCRP identified individuals at elevated long-term risk through independent pathways, with consistent relative risk gradients but divergent absolute risks across ethnicities.
Shi H, Cheng S, Sun D
… +15 more, Han Y, Yu C, Sun D, Pei P, Yang L, Chen Y, Du H, Chen L, Schmidt D, Chen J, Chen Z, Li L, Wei J, Lv J, China Kadoorie Biobank Collaborative Group
J Am Coll Cardiol
· 2026 Jun · PMID 42340288
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BACKGROUND: Evidence linking components of particulate matter with diameters ≤2.5 μm (PM) to the incidence of cardiovascular disease (CVD) remains scarce and inconsistent. OBJECTIVES: The aim of this study was to investi...BACKGROUND: Evidence linking components of particulate matter with diameters ≤2.5 μm (PM) to the incidence of cardiovascular disease (CVD) remains scarce and inconsistent. OBJECTIVES: The aim of this study was to investigate the associations of long-term exposure to PM components with incident CVD risk, considering both absolute concentrations and relative proportions. METHODS: This study included 487,037 participants from the China Kadoorie Biobank who were free of CVD or cancer at baseline. Three-year moving average concentrations of PM and its components (black carbon [BC], organic matter, chloride [Cl], nitrate [NO], sulfate [SO], and ammonium [NH]) were geocoded to participants at 1 × 1 km resolution according to their community recruitment clinic locations. Time-varying Cox proportional hazards models were used to evaluate the associations between PM components and incident CVD risk. Substitution models were used to estimate the effects of reallocating PM component proportions while keeping total PM mass constant, thereby evaluating changes in CVD risk associated with shifts in component composition. RESULTS: Over a median 15.1-year follow-up, a total of 196,224 CVD cases, including 72,747 of ischemic heart disease, 74,594 of ischemic stroke, 17,553 of hemorrhagic stroke, and 54,306 of other cerebrovascular diseases, were documented. Long-term exposure to PM components was associated with increased risk for CVD and its major subtypes. For total CVD, the HRs per IQR increase were 1.15 (95% CI: 1.13-1.17) for BC, 1.17 (95% CI: 1.15-1.18) for organic matter, 1.28 (95% CI: 1.25-1.32) for Cl, 1.29 (95% CI: 1.24-1.33) for NO, and 1.23 (95% CI: 1.20-1.25) for SO. Higher proportions of Cl, SO, and BC were associated with an increased risk for ischemic stroke, and the aforementioned inorganic ions were also positively associated with ischemic heart disease. Substituting 1% of any other PM component with Cl was associated with a 3% to 8% higher risk for total CVD, whereas substitutions with BC were associated with a 1% to 8% higher risk for ischemic stroke, and substitution with SO was associated with a 2% to 5% higher risk for ischemic heart disease. CONCLUSIONS: Long-term exposure to PM chemical components was positively associated with CVD risk. Critically, CVD risk was influence by compositional shifts, with a particularly hazardous profile characterized by higher proportions of Cl, BC, or SO. These findings underscore the importance of implementing targeted, health-oriented control strategies that prioritize specific PM components.
El-Hamamsy I, Chauvette V, Bouhout I
… +3 more, Louro K, Poirier N, Demers P
J Am Coll Cardiol
· 2026 Jun · PMID 42339796
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BACKGROUND: With renewed enthusiasm for the Ross procedure in adults in recent years, long-term data using contemporary techniques are needed. OBJECTIVES: The purpose of this study was to evaluate long-term clinical and...BACKGROUND: With renewed enthusiasm for the Ross procedure in adults in recent years, long-term data using contemporary techniques are needed. OBJECTIVES: The purpose of this study was to evaluate long-term clinical and echocardiographic outcomes of the Ross procedure in a contemporary adult cohort. METHODS: From 2011 to 2019, 455 consecutive adults (mean age 47 ± 12 years; 73% male) underwent a Ross procedure at a single high-volume tertiary center. This includes our inaugural experience with the procedure. All patients were prospectively followed with systematic clinical and echocardiographic follow-up. Outcomes included operative safety, long-term survival, reinterventions, valve hemodynamics, and autograft root dimensions. Median follow-up was 9.0 years (Q1-Q3: 7.3-11.1 years), with 98% completeness of clinical and echocardiographic follow-up (4,191 patient-years and 2,921 echocardiograms). RESULTS: Operative mortality was 0.4% (n = 2). No patient-prosthesis mismatch occurred, and permanent pacemaker implantation was required in 0.8% (n = 3). At 12 years, actuarial survival was comparable to the age- and sex-matched general population. The cumulative incidence of autograft reintervention at 12 years was 1.1% ± 0.5%, with no difference between patients with preoperative aortic regurgitation and aortic stenosis (1.2% ± 1.2% vs 1.1% ± 0.6%; P = 0.39, respectively). The cumulative incidence of pulmonary homograft reintervention at 12 years was 1.9% ± 0.9%, and any cardiac reintervention was 3.5% ± 1.0% at 12 years. Mean aortic valve gradient at 12 years was 4.0 ± 0.2 mm Hg. CONCLUSIONS: In a large contemporary adult cohort with comprehensive follow-up, the Ross procedure was associated with excellent long-term survival, durable valve performance, and low reintervention rates, including in patients with preoperative aortic regurgitation and those >50 years of age. These findings provide an important contemporary benchmark and support broader consideration of the Ross procedure in appropriately selected adults in experienced centers.