J Am Coll Cardiol
· 2026 Jun · PMID 42233552
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BACKGROUND: Cardiovascular disease increases risks of chronic kidney disease (CKD) progression and mortality in type 2 diabetes. OBJECTIVES: The study sought to assess semaglutide effects on kidney and survival outcomes...BACKGROUND: Cardiovascular disease increases risks of chronic kidney disease (CKD) progression and mortality in type 2 diabetes. OBJECTIVES: The study sought to assess semaglutide effects on kidney and survival outcomes by baseline cardiovascular status in the FLOW trial. METHODS: 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 ≥20%). The primary outcome was ≥50% estimated glomerular filtration rate (eGFR) decline, eGFR <15 mL/min/1.73 m, dialysis, transplantation, and kidney or cardiovascular death. All-cause death was a confirmatory secondary outcome. RESULTS: 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 ≥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). CONCLUSIONS: 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).
Ioannou A, Patel R, Mansell J
… +23 more, Sheikh A, Thillainathan B, Razvi Y, Martinez-Naharro A, Venneri L, Lane T, Petrie A, Moon J, Manisty C, Lachmann H, Hawkins PN, Galpert J, Keene D, Kellman P, Solomon SD, Knight DS, Kotecha T, Lockie T, Patel N, Khiani R, Wechalekar A, Gillmore JD, Fontana M
J Am Coll Cardiol
· 2026 May · PMID 42201646
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BACKGROUND: 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...BACKGROUND: 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. OBJECTIVES: The purpose of this study was to prospectively characterize arrhythmic burden using implantable loop recorders and explore associations with amyloid subtype and disease characteristics. METHODS: In this prospective single-center observational study, 110 treatment-naïve 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. RESULTS: 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. CONCLUSIONS: 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).
Aday AW, Eden SK, Kundu S
… +8 more, Greevy RA, Anderson-Mellies A, Alba PR, Alcorn CW, Sullivan AE, Tindle HA, Beckman JA, Freiberg MS
J Am Coll Cardiol
· 2026 May · PMID 42201289
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BACKGROUND: 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 st...BACKGROUND: 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. OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Butler J, Kahwash R, Khan MS
… +14 more, Zhang D, Dukes JW, Reddy M, Basuray A, Gharib E, Gerritse B, Laechelt A, Wehking J, Sarkar S, Van Dorn B, Patel N, Laager V, Zile MR, ALLEVIATE-HF Investigators
J Am Coll Cardiol
· 2026 Jun · PMID 42201288
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BACKGROUND: Early identification of worsening heart failure (HF) may improve outcomes. OBJECTIVES: This study aims to assess if insertable cardiac monitor (ICM)-based high-risk detection combined with centrally managed,...BACKGROUND: Early identification of worsening heart failure (HF) may improve outcomes. OBJECTIVES: 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. METHODS: 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. RESULTS: 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 ± 8.9 months, the serious adverse events rate was 0.32% (95% CI: 0.10%-0.99%; prespecified safety threshold ≤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). CONCLUSIONS: 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).
Yao Z, Dardari ZA, LaMonte MJ
… +23 more, Matsushita K, Ballantyne CM, Lima JA, Vasan RS, Simonsick EM, Appel LJ, Cohen DL, Judd S, Cawthon PM, Shah AM, Weber BN, Cao T, Dzaye O, Tasdighi E, Jelwan Y, Jha KK, Psaty BM, Bis JC, Olson NC, Lash JP, Cushman M, Eaton CB, Blaha MJ
J Am Coll Cardiol
· 2026 May · PMID 42201287
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BACKGROUND: 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 r...BACKGROUND: 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. OBJECTIVES: 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. METHODS: 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. RESULTS: Among 59,396 participants, the median IL-6 concentration was 1.91 pg/mL. The mean age was 63.6 ± 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. CONCLUSIONS: 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.
Al-Kindi S, Ayers MP, Ayuba G
… +18 more, Cavender MA, Guha A, Fradley M, Khraishah H, McGrath L, Minhas A, Montgomery R, Reza N, Syed FF, Weber B, Albert CM, Cappola TP, Cigarroa JE, Gerszten RE, Lohr NL, Prabhu SD, Rajagopalan S, Association of Professors in Cardiology
J Am Coll Cardiol
· 2026 May · PMID 42201285
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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. Thes...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.
Kahwash R, Butler J, Khan MS
… +15 more, Zhang D, Dukes J, Reddy M, Kaplan RM, Amin A, Kanwar R, Sarkar S, Laager V, Wehking J, Van Dorn B, Gerritse B, Patel N, Laechelt A, Zile MR, ALLEVIATE-HF Investigators
J Am Coll Cardiol
· 2026 Jun · PMID 42201276
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BACKGROUND: Arrhythmia burden in ambulatory patients with symptomatic heart failure (HF) without cardiac implantable electronic devices (CIEDs) is not well defined, and it remains uncertain whether device-guided remote c...BACKGROUND: Arrhythmia burden in ambulatory patients with symptomatic heart failure (HF) without cardiac implantable electronic devices (CIEDs) is not well defined, and it remains uncertain whether device-guided remote congestion management modifies arrhythmia occurrence. OBJECTIVES: The goal was to assess whether arrhythmia burden differed between randomized congestion-management strategies and characterize the occurrences and associations of insertable cardiac monitor (ICM)-detected arrhythmias with therapeutic actions and clinical events. METHODS: In ALLEVIATE-HF, patients with NYHA functional class II-III HF with any ejection fraction (EF) and a recent HF event, without prior CIEDs, underwent ICM implantation and were randomized to ICM-guided, physician-directed, nurse-facilitated congestion management or usual care. In both arms, arrhythmia data were accessible to investigators, and arrhythmia-related management was clinician directed. Arrythmia occurrence was estimated using Kaplan-Meier methods. Associations with therapeutic interventions and clinical events were evaluated using time-varying Cox models. RESULTS: The analysis included 711 patients (mean age 70.5 ± 10.4 years; 45.7% women; mean follow-up 17.3 ± 8.9 months); 67.9% had HF with preserved EF, and 60.2% were NYHA functional class II at baseline. During the 13-month randomized phase, arrhythmia occurrence rate did not differ between the study arms. The 3-year overall occurrence of atrial fibrillation (AF) was 66.6%, with an incidence of new-onset AF of 25.4%. Bradyarrhythmia occurred in 47.1% of patients, and ventricular tachycardia or fibrillation (VT/VF) in 20.1%. ICM-recorded arrhythmia was associated with subsequent increase in arrhythmia-related interventions (HR: 3.81; VT/VF and VT/VF-related interventions, HR: 7.04; AF and AF-related interventions, HR: 3.28; bradyarrhythmia and bradyarrhythmia-related interventions, HR: 7.22; all P < 0.001). ICM-recorded arrhythmia was associated with increased risk of all-cause hospitalization (HR: 1.79; P < 0.001) and HF events (HR: 1.69; P = 0.003). Therapeutic CIED implantation and ablation occurred in 22.7% and 26.1%, respectively. Bradyarrhythmias were more common in patients with EF ≥50%, whereas VT/VF occurred more frequently in EF <50%; AF occurrence was similar between EF groups. CONCLUSIONS: In ambulatory patients with recent symptomatic HF events, arrhythmia burden was not modified by the study protocol-directed, congestion-management strategy. Continuous ICM monitoring revealed a high burden of clinically meaningful arrhythmias that were associated with clinical events and therapeutic interventions. (Algorithm Using LINQ Sensors for Evaluation And Treatment of Heart Failure [ALLEVIATE-HF]; NCT04452149).
Bruno J, Arrigo M, Baudry G
… +19 more, Biegus J, Bozkurt B, Čerlinskaitė-Bajorė K, Cohen LP, Hartshorne-Evans N, Ishihara S, Jessen N, Martens P, Myhre P, Pagnesi M, Rosner C, Sari NY, Savarese G, Skaarup KG, Spahillari A, Ter Maaten JM, Tolppanen H, Januzzi JL, Mebazaa A
J Am Coll Cardiol
· 2026 Jun · PMID 42201275
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Acute heart failure (AHF) represents a major global health challenge, with a substantial impact on survival, morbidity, and health care resource utilization. The clinical and economic burden associated with this conditio...Acute heart failure (AHF) represents a major global health challenge, with a substantial impact on survival, morbidity, and health care resource utilization. The clinical and economic burden associated with this condition continues to grow, highlighting the need for a timely, structured, and patient-centered approach to care. In light of the expanding body of data and evidence accumulated over recent years, it is necessary to rethink how we approach the recognition and management of AHF. This need has motivated the development of the present review, which aims to provide an updated and practical synthesis of the management of AHF-from early diagnostic assessment and decongestive strategies to the initiation of guideline-directed medical therapy and planning for outpatient transition. The goal is to outline an integrated, holistic, and patient-centered care pathway to facilitate timely recognition and access to guideline-directed medical therapies for AHF. This document is the result of collaboration among an international panel of clinicians with expertise in AHF management. The aim is to offer guidance that is globally applicable across a wide range of clinical settings. Particular attention has been paid to ensuring that the proposed recommendations reflect diverse health care needs while addressing key challenges and threats in the management of patients with AHF. By aligning clinical strategies with patient needs and system capabilities, this review seeks to advance the quality and consistency of AHF care worldwide.