Beck AW, Desai ND, Abel D
… +34 more, Abraham CZ, Bavaria JE, Browndyke JN, Clough RE, Collet JP, Cutlip DE, Czerny M, Eagleton MJ, Estrera AL, Fleischmann D, Haulon S, Heijmen RH, Kim KM, Kölbel T, Krucoff MW, Lansky AJ, Leshnower BG, Lyden SP, Mack M, Mastracci TM, Matsumura JS, Mehran R, Melissano G, Messé SR, Morice MC, Nienaber CA, Oderich GS, Ouriel K, Ouzounian M, Preventza O, Resch TA, Roselli EE, Spitzer E, Piazza G
Circulation
· 2026 Jun · PMID 42224373
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Innovation in the treatment of ascending aorta and arch pathology with novel catheter-based and hybrid procedures has driven the need for a strategy to guide their safe application. The ARCH-ARC (Aortic Arch Academic Res...Innovation in the treatment of ascending aorta and arch pathology with novel catheter-based and hybrid procedures has driven the need for a strategy to guide their safe application. The ARCH-ARC (Aortic Arch Academic Research Consortium) was established to pragmatically develop consistent clinical end points and to standardize definitions for use in studies of these new technologies. The ARCH-ARC team, consisting of independent international specialists in cardiac surgery, vascular surgery, vascular medicine, cardiology, neurology, radiology, and clinical trials, along with US Food and Drug Administration, industry, and contract research organization representatives, held virtual meetings from 2021 to 2025. Consensus was used to identify appropriate clinical end points and to standardize definitions of end points for endovascular, hybrid, and open surgical procedures in clinical trials in the ascending aorta and arch. Drawing on previous ARC work in cardiac, neurological, renal, and bleeding end points, the ARCH-ARC focused on definitions and end points related to aortic arch-specific anatomy, pathology, and procedures and clinical, device, and imaging. The adoption of the ARCH-ARC consensus definitions and end points will provide a template for consistent adjudication and event reporting and facilitate comparisons of clinical research studies involving devices for ascending aorta and arch pathology.
Swift DL, Ross LM, Laddu DR
… +6 more, Conroy MB, German CA, Evangelista LS, Marvel FA, Jerome GJ, on behalf the American Heart Association Council on Lifestyle and Cardiometabolic Health; Council on Cardiovascular and Stroke Nursing; Council on Clinical Cardiology; Council on Hypertension; and Stroke Council
Circulation
· 2026 Jun · PMID 42220241
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Weight loss and weight loss maintenance are prominent topics of discussion for clinicians and health professionals involved in treatment to reduce obesity and the risk of cardiovascular disease. Because physical activity...Weight loss and weight loss maintenance are prominent topics of discussion for clinicians and health professionals involved in treatment to reduce obesity and the risk of cardiovascular disease. Because physical activity is a key component of comprehensive obesity treatment, this scientific statement summarizes the role of physical activity in promoting weight loss, weight loss maintenance, and cardiometabolic health, complementing lifestyle, pharmacological, and surgical-based weight loss intervention strategies. Independently of weight loss, physical activity and exercise programs improve major cardiometabolic risk factors, including hypertension, insulin resistance, and dyslipidemia, which are highly prevalent in patients with overweight or obesity. As a single treatment modality, physical activity and exercise programs are unlikely to result in clinically meaningful weight loss (ie, at least 5% loss of initial body weight) unless aerobic physical activity levels are exceptionally high. When combined with diet-induced negative energy balance, obesity medication, or surgical treatment, increased physical activity can augment total weight loss and improve cardiometabolic outcomes. Because clinicians and health professionals play a pivotal role in fostering and sustaining patients' health goals, this scientific statement also provides an overview of evidence-based strategies for targeted weight loss counseling and for leveraging digital technology, particularly to engage patients and achieve realistic physical activity goals.
Winters AH, Kelly MA, Syed MG
… +8 more, Bergquist T, Berry ASF, Mohammed N, Cawley D, Jones LK, Pejaver V, Gidding SS, Oetjens MT
Circulation
· 2026 Jun · PMID 42212376
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BACKGROUND: Familial hypercholesterolemia (FH) is an inherited disorder characterized by lifelong elevated LDL-C (low-density lipoprotein cholesterol) and increased risk for premature myocardial infarction. FH research h...BACKGROUND: Familial hypercholesterolemia (FH) is an inherited disorder characterized by lifelong elevated LDL-C (low-density lipoprotein cholesterol) and increased risk for premature myocardial infarction. FH research has focused on European populations and, consequently, estimates of global FH burden primarily reflect this ancestry, with limited data available from other groups. METHODS: We examined the prevalence and clinical outcomes of FH among 104 300 African ancestry individuals enrolled in 3 US-based cohorts: the National Institutes of Health's All of Us, Mount Sinai's BioMe, and Geisinger's MyCode. Genetic variants were evaluated according to standards provided by the Clinical Genome Resource's FH Variant Curation Expert Panel and grouped as pathogenic variants or variants of unknown significance (VUSs). Participants were assigned to European and African ancestry groups based on genetic similarity to reference populations. Clinical outcomes were LDL-C and myocardial infarction. Analyses were adjusted for age and sex. Results were meta-analyzed across cohorts. RESULTS: The prevalence of a pathogenic variant was similar in the African (1 in 306) and European (1 in 273) ancestry groups. The LDL-C elevation associated with pathogenic variants was 20.81 mg/dL (95% CI, 16.17-25.45) greater in individuals with African ancestry compared with their counterparts with European ancestry. Individuals with African ancestry had 1.61 (95% CI, 1.42-1.83; =1.2×10) higher odds of having a VUS compared with individuals with European ancestry and a 10.01 mg/dL (95% CI, 6.13-13.88) greater elevation in LDL-C compared with individuals with European ancestry with a VUS. Although pathogenic variants in both ancestries conferred a 2- to 3-fold increased risk of myocardial infarction, having a VUS only conferred increased risk among the African ancestry group (odds ratio, 1.91 [95% CI, 1.18-3.10]). CONCLUSIONS: The prevalence of pathogenic variants did not significantly vary between African and European ancestry groups. VUSs were both more prevalent among individuals of African ancestry and associated with an increased risk of myocardial infarction equivalent to that of a pathogenic variant. These findings suggest that dependence on existing resources for variant classification could contribute to underdiagnosis of FH in individuals of African ancestry.
BACKGROUND: Acute decompensated heart failure (ADHF) exhibits seasonal variations, yet the short-term effects of ambient temperature, independent of seasonality, remain poorly studied. Moreover, temperature-sensitive exa...BACKGROUND: Acute decompensated heart failure (ADHF) exhibits seasonal variations, yet the short-term effects of ambient temperature, independent of seasonality, remain poorly studied. Moreover, temperature-sensitive exacerbation phenotypes are not well defined, limiting the development of effective preventive strategies. We aimed to investigate the effects of ambient temperature on ADHF admissions and clinical presentation profiles. METHODS: We included 26 874 patients with ADHF who had been registered in the Tokyo Cardiovascular Care Unit Network Database between January 2014 and December 2019. The onset date of ADHF leading to hospitalization, along with clinical characteristics such as age, left ventricular function, cause of ADHF, and hemodynamic profile, was assessed by cardiologists at each participating center. Climate data were obtained from an observatory near the admitting hospital. We used a time-stratified case-crossover design with distributed lag nonlinear models to explore the association between ambient temperature and ADHF admissions over lag days 0 to 5, with stratified analyses by the clinical presentations. RESULTS: Exposure to extremely low temperatures (-4.5 °C [first percentile]) increased the risk of ADHF (1.80, 95% CI, 1.40-2.31) when referenced to the temperature of lowest risk (29.0 °C [99th percentile]). The excess risk of lower temperature appeared immediately on the day of exposure (lag 0). This risk was larger in patients aged ≥70 years and otherwise consistent across subgroups. Notably, the temperature-risk relationship differed by hemodynamic profiles; risk for ADHF with hypertension rose at low temperatures, whereas ADHF with low blood pressure showed the opposite pattern, with risk increasing at high temperatures (odds ratio, 6.25 [95% CI, 1.07-36.6] at the 99th percentile). CONCLUSIONS: Low ambient temperature increased ADHF risk, especially in older adults, while temperature effects differed by hemodynamic phenotype. Incorporating temperature exposure into risk assessment may enable targeted prevention of climate-related decompensation. REGISTRATION:URL: https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000015310; Unique identifier: UMIN000013128.
Desai AS, Zile MR, Ducharme A
… +11 more, Mehra MR, Maisel AS, Sears SF, Costanzo MR, Smart FW, Chien CV, Jonsson O, Hall S, Nie H, Lee FS, Lindenfeld J
Circ Heart Fail
· 2026 Jun · PMID 42206402
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BACKGROUND: While clinical benefits of guideline-directed medical therapy in patients with heart failure (HF) are well established, acute hemodynamic changes after initiation of these agents are not well described. Wirel...BACKGROUND: While clinical benefits of guideline-directed medical therapy in patients with heart failure (HF) are well established, acute hemodynamic changes after initiation of these agents are not well described. Wireless pulmonary artery pressure (PAP) monitoring using implantable sensors is ideally suited to determine changes in pressure following medication titration. METHODS: We compared PAP from 7 days pre-initiation to the 7-day period following 30 days of newly initiated treatment with core HF therapies: angiotensin receptor-neprilysin inhibitors, mineralocorticoid receptor antagonists, sodium-glucose co-transporter-2 inhibitors, and β-blockers in patients implanted with a PAP sensor (CardioMEMS, Abbott) as part of the GUIDE-HF study (Hemodynamic-Guided Management of HF). Patients with changes in loop diuretics or other core HF therapies during the 30-day interval were excluded from the analysis. RESULTS: Of 2358 patients in the study, 50 patients had new angiotensin receptor-neprilysin inhibitor initiation, 97 patients had new sodium-glucose co-transporter-2 inhibitor initiation, 112 patients had new mineralocorticoid receptor antagonist initiation, and 33 had new β-blocker initiation at least 30 days post-implant, continued to take the medication for at least 30 days, and were included in this analysis. Following angiotensin receptor-neprilysin inhibitor or mineralocorticoid receptor antagonist initiation, diastolic PAP decreased by -1.56 (95% CI, -3.54 to -0.40) and -1.15 (95% CI, -1.82 to -0.47) mm Hg, respectively, in the absence of changes in loop diuretics or other core HF therapies. By contrast, there was no detectable change in PAP following the new initiation of the sodium-glucose co-transporter-2 inhibitor. A trend to higher PAP was observed after β-blocker initiation though differences were not significant. CONCLUSIONS: These results may inform the selection of pharmacological therapy to manage elevated filling pressures during hemodynamic-guided therapy. REGISTRATION:URL: https://www.clinicaltrials.gov; Unique identifier: NCT03387813.
Neyazi M, Venturini G, Brown KJ
… +24 more, Choi Y, Gorham JM, Layton OG, Verma A, Wang AJ, Gross RT, McDonough BA, Mendiola Pla M, Viveiros A, DeLaughter DM, DePalma SR, Kim Y, Reichart D, Wakimoto H, Elledge SJ, Divakaran S, Mitchell RN, Koh J, Park JB, Bowles DE, Glass C, Oudit GY, Seidman JG, Seidman CE
Circulation
· 2026 Jun · PMID 42206386
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BACKGROUND: Cardiac sarcoidosis (CS) is an enigmatic disorder characterized by unexplained patchy, sterile granulomas intermixed with preserved myocardium and fibrotic regions without granuloma. CS causes arrhythmias, su...BACKGROUND: Cardiac sarcoidosis (CS) is an enigmatic disorder characterized by unexplained patchy, sterile granulomas intermixed with preserved myocardium and fibrotic regions without granuloma. CS causes arrhythmias, sudden cardiac death, and heart failure. The mechanisms producing this remarkable histopathology and disease progression remain unexplained. METHODS: Using comprehensive single-cell and spatial transcriptomic analyses, we characterized the cellular composition and gene expression in preserved, granulomatous, and fibrotic regions of human CS hearts. From unexpectedly identified clonally expanded cardiac B cells with rearranged immunoglobulin sequences, we reconstructed antibodies and screened libraries comprising the human peptidome or microbial and allergen peptides to define reactive epitopes in CS hearts. RESULTS: Cellular composition and gene expression differed substantially in CS tissues with preserved, granulomatous, or fibrotic histopathology. Cardiomyocytes upregulated arrhythmogenic and inflammasome transcripts associated with pyroptosis. Cardiomyocytes and fibroblasts activated chemoattractant cytokines that sustained myeloid and lymphoid infiltration. Granulomas contained abundant macrophages expressing modulators of cell-cell fusion, along with Th17-skewed T cells that upregulated B-cell-activating factor, thereby promoting antibody production. Fibrotic regions, without active granulomas, exhibited tertiary lymphoid structures, with clonal expansion of mature B and plasma cells. Reconstructed antibodies derived from expanded B-cell clones were inert to microbial and allergen peptides, but reacted to PPL (periplakin), a desmosome protein, and other peptides expressed on cardiac cells. CONCLUSIONS: Progressive inflammatory signals in CS are mediated by chemoattractant genes in cardiomyocytes and fibroblasts within preserved myocardium, cell-cell fusion modulators in activated macrophages within granulomatous regions, and tertiary lymphoid structures in fibrotic regions that produce patient-specific autoimmune antibodies. Identification of PPL as a CS autoantigen may account for shared clinical manifestations in CS and arrhythmic desmosomal cardiomyopathies. CS autoantigens may underlie enigmatic histopathologic findings, perpetuate disease, and contribute to adverse outcomes. Uncovering an intracardiac humoral autoimmune axis in CS provides specific therapeutic opportunities to limit granuloma formation and B-cell activation, which may reduce arrhythmogenicity and progressive dysfunction. Parallel analytic strategies have potential to define autoantigens in other enigmatic cardiac immune disorders.
Khazanie P, Drazner MH, Breathett K
… +10 more, Cohen IG, Fraser M, Khush KK, Mohammed SF, Rogers JG, Shah AS, St Laurent P, Truby LK, Fedson SE, American Heart Association Heart Failure and Transplantation Committee of the Council on Clinical Cardiology; Council on Cardiovascular and Stroke Nursing; Council on Cardiovascular Surgery and Anesthesia; and Council on Quality of Care and Outcomes Research
Circulation
· 2026 May · PMID 42206385
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The heart transplant allocation system is evolving in response to increasing demand for donor organs, technological advances, and changes in medical decision-making. In this evolving landscape, the historical focus of al...The heart transplant allocation system is evolving in response to increasing demand for donor organs, technological advances, and changes in medical decision-making. In this evolving landscape, the historical focus of allocating donor hearts to the "sickest patients first" principle may warrant periodic reassessment and thoughtful safeguards to ensure responsible stewardship and fairness. It is important to note that ethical considerations are central to frontline transplantation cardiologists and cardiothoracic surgeons, who must balance their role in advocating for their individual patients while aligning with allocation policies designed to benefit all recipients equitably. The goals of this scientific statement are (1) to raise awareness of ethical principles in heart transplantation, (2) to review ethical implications of the past and current allocation systems, and (3) to encourage clinicians and stakeholders to address ethical issues that will provide the foundation for future allocation systems.
Liu X, Thomas NH, Berliner D
… +18 more, Schwab J, Rieth A, Strack C, Schallhorn S, Soltani S, Haebel L, Geller W, Zdravkovic M, Hülsmann M, von der Leyen H, Veltmann C, Störk S, Böhm M, Bauersachs J, Koch A, Bavendiek U, Großhennig A, DIGIT-HF Study Group
Wang J, Xu J, Mai H
… +7 more, Niu G, Wu S, Zhang X, Zhu J, Aschner M, Meng Q, Chen R
Circulation
· 2026 May · PMID 42206375
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BACKGROUND: Bisphenol F (BPF) is a common substitute for bisphenol A and the most prevalent bisphenol compound in diverse plastic manufacturing applications. However, the potential toxicity of BPF remains largely unexplo...BACKGROUND: Bisphenol F (BPF) is a common substitute for bisphenol A and the most prevalent bisphenol compound in diverse plastic manufacturing applications. However, the potential toxicity of BPF remains largely unexplored. This study investigates the effects of BPF on the cardiovascular system and intestinal barrier. METHODS: Germ-free mouse models and fecal microbiota transplantation techniques were used to confirm the role of gut microbiota in BPF-induced cardiovascular injury. Untargeted metabolomics and spatial metabolomics were used to identify the in vivo metabolic products of BPF. Single-cell sequencing was used to identify which cardiac cell types were damaged by BPF exposure. RESULTS: BPF was detected in 90.5% of 285 human urine samples (median, 1.16 ng/μg creatinine). BPF exposure induced cardiomyocyte hypertrophy, cardiac dysfunction, and intestinal barrier damage, effects contingent on the presence of gut microbiota. Metabolomic analysis identified the microbial conversion of BPF to N-acetylputrescine (NAP). Mechanistically, we found that BPF stimulated intestinal epithelial cells to secrete spermidine/spermine N1-acetyltransferase 1 (Sat1), which catalyzed this conversion. Furthermore, NAP impaired the intestinal barrier by disrupting the Golgi-mitochondria axis and caused cardiac hypertrophy by activating the p53 pathway and inhibiting glycolysis in cardiomyocytes. Supplementation with or its metabolite tryptophol mitigated BPF-induced cardiac and intestinal injuries by downregulating the Sat1-NAP axis. Clinical analysis further showed elevated serum NAP levels in patients with inflammatory bowel disease, positively correlating with cardiac injury markers. CONCLUSIONS: BPF disrupts intestinal barrier function through microbial metabolism involving the tryptophol/Sat1 pathway, leading to NAP production. NAP damages intestinal organelles and enters circulation, inducing cardiac p53 activation and hypertrophy. This study delineates a novel gut microbiota-Sat1-NAP pathway underlying BPF-induced cardiotoxicity, offering new insights for risk assessment and therapeutic intervention.
Circulation
· 2026 Jun · PMID 42200287
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BACKGROUND: Individuals of African ancestry are underrepresented in genetic studies, contributing to disproportionately higher rates of variants of uncertain significance (VUS) and fewer actionable results in genetic tes...BACKGROUND: Individuals of African ancestry are underrepresented in genetic studies, contributing to disproportionately higher rates of variants of uncertain significance (VUS) and fewer actionable results in genetic testing for cardiomyopathies and arrhythmias. We aimed to determine whether ancestry-enriched VUS confer measurable cardiovascular risk among individuals of African ancestry. METHODS: We identified VUS enriched in individuals of African ancestry in 18 cardiomyopathy and arrhythmia genes. We defined enriched as allele frequency in gnomAD ≥2-fold higher than in European (non-Finnish) individuals, and we confined the analysis to VUS with allele frequency >0.05% in individuals of African ancestry. Associations with cardiovascular phenotypes were assessed in 96 897 individuals of African ancestry from the All of Us (n=65 481) and BioVU (n=31 416) biobanks using fixed-effects meta-analysis. Analyses were stratified by heart failure (HF) status and conventional cardiovascular risk factors. RESULTS: We identified 82 ancestry-enriched VUS. Exploratory analysis in All of Us identified 10 variants associated with composite cardiovascular outcome, 4 of which were associated with individual cardiovascular phenotypes in pooled meta-analysis across both cohorts. p.Val558Ile was associated with a 4-fold increased risk of ventricular arrhythmias or sudden cardiac death (adjusted odds ratio [aOR], 4.02 [95% CI, 1.85-8.71]; =0.004). p.Ile396Val was associated with HF (aOR, 1.67 [95% CI, 1.17-2.39]; =0.02) and atrial arrhythmias (aOR, 1.88 [95% CI, 1.27-2.78]; =0.02). p.Gly11Ser and p.Val842Ile were associated with HF (aOR, 1.96 [95% CI, 1.24-3.10]; =0.02 and aOR, 1.99 [95% CI, 1.16-3.41]; =0.039). The presence of cardiovascular risk factors was associated with earlier onset of HF (adjusted hazard ratio, 1.71 [95% CI, 1.25-2.33]; =0.0006) and atrial arrhythmias (adjusted hazard ratio, 1.17 [95% CI, 1.06-1.29]; =0.0019) in pooled variant carriers. p.Val558Ile, p.Gln1832Glu, and p.Gly11Ser demonstrated increased arrhythmia burden specifically in participants with HF. Using American College of Medical Genetics and Genomics guidelines, p.Val558Ile met criteria for likely pathogenic classification, potentially affecting an estimated 24 000 Black adults in the United States. CONCLUSIONS: Large-scale biobank analysis identified variants classified as VUS that conferred increased risk of cardiomyopathy and arrhythmia in individuals with African ancestry. The risk associated with these variants was increased in the presence of cardiovascular risk factors and HF.
Slivnick JA, Lim SC, Randazzo M
… +27 more, Maurer MS, Helmke S, Scherrer-Crosbie M, Vakilpour A, Zareba KM, Goyal A, Cheng R, Nakamatsu N, Kitano T, Takeuchi M, Hotta VT, Campos Vieira ML, Elissamburu P, Ronderos RE, Prado A, Koutroumpakis E, Deswal A, Pursnani A, Sarswat N, Addetia K, Cotella J, Ruberg FL, Frost M, Fontana M, Lam Su Ping C, Lang RM, Asch FM
BACKGROUND: Cardiac amyloidosis (CA) is an underdiagnosed yet treatable cause of heart failure in which timely diagnosis is essential to initiate life-prolonging therapies. While artificial intelligence (AI)-based tools...BACKGROUND: Cardiac amyloidosis (CA) is an underdiagnosed yet treatable cause of heart failure in which timely diagnosis is essential to initiate life-prolonging therapies. While artificial intelligence (AI)-based tools using transthoracic echocardiography (TTE), electrocardiography, or electronic health records have demonstrated promise for CA detection, most rely on single data sources. We aimed to evaluate whether integrating clinical, laboratory, and TTE biomarkers improves the performance of an existing TTE-based AI model for CA detection. METHODS: We developed and tested a combined AI echo-clinical model (AI-ECM) incorporating demographics, laboratory biomarkers, and TTE parameters into a previously validated TTE-only AI model (Us2.Ca). Model training and internal validation were performed using the Amyloidosis Imaging International Consortium, a global multiethnic registry comprised of 727 patients with CA and 316 controls, including 202 with suspected transthyretin-CA with negative diagnostic evaluation and 114 patients with biopsy-proven extracardiac light chain amyloidosis without cardiac involvement. Ground truth CA diagnosis was adjudicated per consensus criteria. AI-ECM and Us2.Ca performance was assessed using area under the curve, accuracy, sensitivity, and specificity. RESULTS: In building the AI-ECM, feature importance analysis showed that having the Us2.Ca prediction scores, relative wall thickness, sex, and estimated glomerular filtration rate contributed most to performance. The AI-ECM demonstrated superior performance (area under the curve, 0.94; accuracy, 90%; sensitivity, 93%; specificity, 85%) compared with the Us2.Ca (area under the curve, 0.89; accuracy, 80%; sensitivity, 76%; specificity, 91%; =0.006). While the Us2.Ca model classification was indeterminate in 9% of the cases, the AI-ECM allowed classification of all cases. The AI-ECM improved sensitivity for light chain-CA detection and maintained high accuracy across subtypes and control groups. CONCLUSIONS: A multiparametric AI model integrating basic clinical, laboratory, and TTE data with the deep learning Us2.Ca improved performance for CA detection over Us2.Ca alone. This approach represents a step toward scalable, AI-guided precision diagnostics for CA in diverse populations.