Circulation最新文献

{"title":"Radiation Vasculopathy of the Coronary Arteries: State-of-the Art Review.","authors":"Jeffrey Xia, Jean Kim, Abhishek Sharma, Benjamin Yang, Prasanna G Alluri, Katelyn Atkins, Eric D Miller, Terence M Williams, Daniel Addison, Amit Arbune, Alvin Chandra, Efstratios Koutroumpakis, Kathleen W Zhang, Vlad G Zaha","doi":"10.1161/CIRCULATIONAHA.126.079541","DOIUrl":"https://doi.org/10.1161/CIRCULATIONAHA.126.079541","url":null,"abstract":"<p><p>Radiation-associated coronary artery disease (RACAD) is a distinct form of coronary artery disease with several specific biological and clinical aspects as well as key knowledge gaps. RACAD is prevalent in patients with cardiac exposure to radiotherapy. As radiotherapy is integral to the effective treatment of many thoracic malignancies, improved long-term survivorship is coupled with increased risk for RACAD. Ionizing radiation induces free radical generation and activation of proinflammatory cascades, leading to endothelial dysfunction and accelerated atherosclerosis. Risks for RACAD are determined both by radiotherapy, including the radiation dose and the proximity of coronary arteries to the radiotherapy field, and by patient-specific factors, such as younger age, higher baseline cardiovascular risk, and concurrent cardiotoxic systemic therapies. Importantly, radiotherapy delivery is highly individualized on the basis of tumor location and treatment strategy, resulting in heterogeneous coronary exposure to radiation and patient-to-patient variability. Clinical presentation may occur early, within 1 to 2 years, especially in patients with higher cardiac radiation doses (eg, lung or esophageal cancer), or after a latency period of 5 to 20 years with lower cardiac dose radiation exposure (eg, left-sided breast cancer). Patients generally present with symptoms similar to conventional coronary artery disease. However, RACAD symptoms may be underrecognized in cancer survivors due to overlapping treatment-related fatigue, pulmonary disease, or competing oncologic symptoms. Diagnosis and management generally follow standard coronary artery disease guidelines while incorporating cancer-specific considerations, such as planned oncologic surgeries, bleeding risk, postradiotherapy complications such as atretic internal mammary arteries, and cardiotoxic effects of systemic cancer therapies. Primary prevention of RACAD is critical, emphasizing advances in precision radiotherapy, including delivery techniques with improved coronary dosimetry, and cardiac shielding. Key knowledge gaps include understanding long-term outcomes with contemporary 3-dimensional conformal radiotherapy techniques, validated cancer-specific risk prediction models on the basis of coronary dosimetry, optimal surveillance protocols, targeted molecular pharmacotherapies, and risk analysis of percutaneous versus surgical management of RACAD. Prospective studies are needed to develop cancer- and dosimetry-specific risk calculators, validating cardioprotective interventions, and improving multidisciplinary cardio-oncology collaboration to optimize early detection of RACAD and timely intervention in the growing population of cancer survivors.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"154 16","pages":"1627-1645"},"PeriodicalIF":41.3,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149223459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Women's Kidney Health in Focus: A Scientific Statement From the American Heart Association.","authors":"Eman Y Gohar, Ester S Oh, Sofia B Ahmed, S Ananth Karumanchi, Roy O Mathew, Sayna Norouzi, Giorgina B Piccoli, Jane F Reckelhoff, Amanda Vinson, Licy L Yanes Cardozo, Silvi Shah","doi":"10.1161/CIR.0000000000001471","DOIUrl":"10.1161/CIR.0000000000001471","url":null,"abstract":"<p><p>Chronic kidney disease is a global epidemic affecting ≈10% of adults worldwide. Women have a higher prevalence of chronic kidney disease than men yet are less likely to progress to kidney failure, to initiate dialysis, or to receive a kidney transplantation, underscoring the influence of biological sex on chronic kidney disease development, progression, treatment response, and outcomes. Women may also respond differently from men to pharmacological therapies, but they remain underrepresented in clinical trials, limiting the evidence base for sex-specific kidney care. Preclinical evidence implicates a role for estrogen receptor signaling in renal physiology and pathophysiology. Women with chronic kidney disease are at increased risk for adverse pregnancy outcomes and hypertensive disorders of pregnancy, and pregnancy complications can also increase future chronic kidney disease risk. Menopause and aging accelerate chronic kidney disease progression in women as a result of declining estradiol and shifts in kidney estrogen receptor profiles. Endocrine and metabolic disorders such as polycystic ovary syndrome increase susceptibility to chronic kidney disease. Family planning, prepregnancy counseling, and antenatal care are essential to support reproductive health in women with chronic kidney disease. Because chronic kidney disease and cardiovascular disease are tightly intertwined, chronic kidney disease is also a leading contributor to cardiovascular mortality in women. Advancing precision kidney medicine for women requires equitable access to kidney care, embedding assessment of reproductive health in chronic care, trial design with adequate power that includes both women and men, and mechanistic studies linking reproductive health to long-term cardiovascular disease and chronic kidney disease development and progression.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":"e640-e653"},"PeriodicalIF":41.3,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148988553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multimodal <i>KCNQ1</i> Variant-Effect Maps Define Ion Channel Mechanisms and Disease Risk.","authors":"M Lorena Harvey, Ellen Osborn, Megan C Lancaster, Jeremy E Smith, Qianyi Shen, Temidayo A Abe, Ruoyi Cai, Ayesha Muhammad, Rose Kannankeril, Tao Yang, Maria E Calandranis, Daniel J Blackwell, Richard E Dolder, Jessa L Aldridge, Matthew R Fleming, Marcia A Blair, Eduardo Soria, Jack W O'Sullivan, Giovanni Davogustto, Brett M Kroncke, Calum A MacRae, Bjorn C Knollmann, Frederick P Roth, Victoria N Parikh, Euan A Ashley, Jamie I Vandenberg, Chai-Ann Ng, Dan M Roden, Andrew M Glazer","doi":"10.1161/CIRCULATIONAHA.126.080900","DOIUrl":"https://doi.org/10.1161/CIRCULATIONAHA.126.080900","url":null,"abstract":"<p><strong>Background: </strong>Variants in the ion channel gene <i>KCNQ1</i> are the leading cause of congenital long QT syndrome (LQTS), a disorder characterized by QT prolongation and risk of fatal arrhythmias. The expanding use of genetic testing has led to the identification of numerous variants of uncertain significance, complicating clinical interpretation and risk stratification. Functional characterization of <i>KCNQ1</i> variants is essential to define their role in long QT syndrome and advance precision medicine in cardiovascular care.</p><p><strong>Methods: </strong>We generated a nearly comprehensive variant library of 13 403 protein-coding variants in <i>KCNQ1</i>. Using 4 pooled assays followed by high-throughput sequencing, we characterized the variants' effects on cell surface abundance and channel function in both the variant-only and heterozygous states. Case-control analyses and data from large-scale biobanks were used to assess the clinical impact of loss-of-function variants on QT prolongation and long QT syndrome. Heterozygous assay results were used to determine dominant-negative effects, which were also evaluated for association with arrhythmia risk. Protein structural clustering of distinct classes of deleterious variants was analyzed.</p><p><strong>Results: </strong>Across the 4 assays, we generated 49 305 functional measurements of <i>KCNQ1</i> variants. Of the 13 403 <i>KCNQ1</i> studied variants, 1757 demonstrated strong pathogenic evidence, and 6660 showed moderate benign evidence. Loss-of-function variants were significantly associated with QT prolongation and long QT syndrome in case-control and biobank analyses. Deleterious variants clustered within distinct structural domains based on their functional classification. A majority of pathogenic variants exhibited dominant-negative effects; these variants were linked to a higher risk of arrhythmia diagnoses than were haploinsufficient variants.</p><p><strong>Conclusions: </strong>This comprehensive <i>KCNQ1</i> functional atlas provides novel functional evidence for most <i>KCNQ1</i> variants of uncertain significance. It also reveals mechanistic principles linking genetic variation to ion channel biology and arrhythmia susceptibility, advancing cardiovascular precision medicine.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":""},"PeriodicalIF":41.3,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149227385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Response by Reinert and Havers-Borgersen to Letter Regarding Article, \"Polycystic Ovarian Syndrome and the Long-Term Risk of Arrhythmias\".","authors":"Marie Sofie Reinert, Eva Havers-Borgersen","doi":"10.1161/CIRCULATIONAHA.126.081468","DOIUrl":"https://doi.org/10.1161/CIRCULATIONAHA.126.081468","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"154 16","pages":"e623-e624"},"PeriodicalIF":41.3,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149223229","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Defining Meaningful Treatment Responses in Hypertrophic Cardiomyopathy: Seeking a Trifecta Across Phenotypes.","authors":"Andrew Wang","doi":"10.1161/CIRCULATIONAHA.126.082802","DOIUrl":"10.1161/CIRCULATIONAHA.126.082802","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":"1560-1562"},"PeriodicalIF":41.3,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148839383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Future in the Room: TAVR, Surgery, and the Tyranny of the Now.","authors":"Marco Barbanti, Francesco Maisano","doi":"10.1161/CIRCULATIONAHA.126.080256","DOIUrl":"https://doi.org/10.1161/CIRCULATIONAHA.126.080256","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"154 16","pages":"1545-1546"},"PeriodicalIF":41.3,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149223168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Updated Evidence Assessment of the Genetic Causes of Dilated Cardiomyopathy.","authors":"Elizabeth Jordan, Phoenix Grover, Patricia Parker, Jason Cowan, Babken Asatryan, Tomohiko Ai, Akos Berthold, Lucas Bronicki, Emily Brown, Rudy Celeghin, Matthew Edwards, Judith Fan, Cynthia A James, Renee Johnson, Daniel P Judge, Sean Jurgens, Najim Lahrouchi, Tom Lumbers, Francesco Mazzarotto, Argelia Medeiros Domingo, Brittney Murray, Stacey Peters, Kalliopi Pilichou, Alexandros Protonotarios, Karin van Spaendonck-Zwarts, Petros Syrris, Jessica Wang, Roddy Walsh, James S Ware, Ray E Hershberger","doi":"10.1161/CIRCULATIONAHA.126.080302","DOIUrl":"10.1161/CIRCULATIONAHA.126.080302","url":null,"abstract":"<p><strong>Background: </strong>Evidence of the diverse genetic architecture of dilated cardiomyopathy (DCM) continues to emerge and requires reassessment of the clinical relevance of implicated disease genes. Building on the 2019-2020 Clinical Genome Resource evaluation, the DCM gene curation expert panel reconvened in 2024-2025 to conduct a reassessment of genes in DCM.</p><p><strong>Methods: </strong>The Clinical Genome Resource semiquantitative clinical validity classification framework was applied with specifications to DCM to classify genes into categories on the basis of strength of published evidence for a DCM phenotype. Previously curated genes were reassessed, and newly reported gene-disease-mode of inheritance (MOI) relationships, termed \"curations,\" were evaluated.</p><p><strong>Results: </strong>Sixty-eight genes were evaluated, inclusive of 72 unique gene-disease-MOI relationships across 51 previously evaluated and 17 newly assessed genes. Thirty-five curations were classified as high evidence (16 Definitive, 10 Strong, 9 Moderate), increasing by 16 from the prior assessment. Nine newly assessed genes were classified as high evidence: <i>BAG5</i>, <i>FLII</i>, <i>LMOD2</i>, <i>MYLK3</i>, <i>MYZAP</i>, <i>NRAP</i>, <i>PPA2</i>, <i>PPP1R13L</i>, and <i>RPL3L</i>. Twelve genes (11 newly appraised) were rated as high evidence with an autosomal recessive (AR) MOI. Five reevaluated genes from 2019-2020 had clinically significant changes in classification. Except for <i>JPH2</i>, for which curation was modified to separate autosomal dominant and AR MOI curations, clinically significant changes involved upgrades from low- to high-evidence categories (<i>PLEKHM2</i>, <i>PRDM16</i>, <i>TBX20</i>, <i>TNNI3K</i>), demonstrating the robustness of the Clinical Genome Resource gene curation process over time. An additional 29 gene-disease-MOI curations were classified as Limited, including 6 newly evaluated genes and 1 new MOI for a previously evaluated gene, <i>MYBPC3</i>-AR; 4 were classified as No Known Disease Relationship, and remained Disputed. Four previously evaluated genes were curated for both AD and AR MOIs: <i>JPH2</i> (AD-Strong, AR-Limited), <i>LDB3</i> (AD-Limited, AR-Strong), <i>MYBPC3</i> (AD-Limited, AR-Limited), and <i>TNNI3</i> (AD- and AR- Strong).</p><p><strong>Conclusions: </strong>With substantial new evidence, the genetic architecture of DCM has rapidly expanded. This updated assessment of genes reported in DCM yielded 35 high-evidence curations, an increase from 19 only 5 years ago. The results of this evidence-based evaluation process inform clinical interpretation of genetic information in the care of DCM patients and families.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":"1592-1603"},"PeriodicalIF":41.3,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148905238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Finding Time to Relax: The Diastolic Signature of Aficamten in Nonobstructive Hypertrophic Cardiomyopathy.","authors":"Nosheen Reza","doi":"10.1161/CIRCULATIONAHA.126.082804","DOIUrl":"10.1161/CIRCULATIONAHA.126.082804","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":"1577-1579"},"PeriodicalIF":41.3,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148849657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of Anselamimab on Cardiac Structure and Function in Patients With Light Chain Amyloidosis: Insights From the CARES Clinical Trials.","authors":"Xiaowen Wang, Marianna Fontana, Brian Claggett, Karola S Jering, Hicham Skali, Mathew S Maurer, Piero Ricchiuto, Chen Yao, Hrishikesh Kulkarni, Haihong Li, Michele F Mercuri, Candida Cristina Quarta, Scott D Solomon","doi":"10.1161/CIRCULATIONAHA.126.082847","DOIUrl":"10.1161/CIRCULATIONAHA.126.082847","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":"1624-1626"},"PeriodicalIF":41.3,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148857109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HNRNPK Lactylation Amplifies Inflammation and Exacerbates Myocardial Ischemia/Reperfusion Injury by Regulating Jag2 Splicing.","authors":"Suyun Chen, Siman Shen, Wenmei Su, Linhang Fu, Jianning Chen, Li Xu, Ziqiang Yang, Simeng Li, Kun Ding, Yulong Zhang, Ruizhao Shao, Yaofeng Wen, Jing Tang, Yang Wang, Fu-Li Xiang, Liangqing Zhang","doi":"10.1161/CIRCULATIONAHA.126.081410","DOIUrl":"10.1161/CIRCULATIONAHA.126.081410","url":null,"abstract":"<p><strong>Background: </strong>Myocardial ischemia/reperfusion injury triggers profound metabolic reprogramming and lactate accumulation. However, how this metabolic stress regulates inflammatory gene expression remains poorly understood. We hypothesized that lactylation, a lactate-derived posttranslational modification, links metabolic stress to aberrant RNA splicing and cardiac inflammation through the RNA-binding protein HNRNPK (heterogeneous nuclear ribonucleoprotein K).</p><p><strong>Methods: </strong>We analyzed atrial tissues from patients undergoing cardiopulmonary bypass and murine ischemia/reperfusion hearts to assess lactylation dynamics. Lactylation-specific proteomics, RNA sequencing, and crosslinking and immunoprecipitation followed by quantitative polymerase chain reaction were used to identify HNRNPK targets. Mechanisms were defined using site-directed mutagenesis (HNRNPK-K405R), isoform-specific overexpression, and a therapeutic splice-switching antisense oligonucleotide in mice and cardiomyocytes.</p><p><strong>Results: </strong>Reperfusion significantly increased global protein lactylation in human and murine myocardium. Proteomics identified HNRNPK as a key target, specifically lactylated at lysine 405 (K405la). Ischemia-induced K405la promoted HNRNPK binding to <i>Jag2</i> pre-mRNA, suppressing exon 10 skipping and shifting splicing from the <i>Jag2</i> (<i>Jagged2</i>) short (<i>Jag2</i>-S) to the long (<i>Jag2</i>-L) isoform. Jag2-L, but not Jag2-S, exhibited high affinity for Notch1, hyperactivating Notch-NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) signaling and exacerbating inflammation and infarct size. Mice expressing a lactylation-deficient variant (HNRNPK-K405R) were protected from ischemia/reperfusion injury. Treatment with a specific antisense oligonucleotide (Jag2-i9) that blocks the HNRNPK-<i>Jag2</i> interaction prevented Jag2-L production and attenuated cardiac dysfunction.</p><p><strong>Conclusions: </strong>HNRNPK lactylation acts as a metabolic sensor coupling lactate accumulation to pathogenic <i>Jag2</i> splicing. Targeting this metabolic-splicing axis offers a precise therapeutic strategy to limit inflammation and preserve cardiac function in ischemic heart disease.</p><p><strong>Registration: </strong>URL: http://www.chictr.org.cn; Unique identifier: ChiCTR2400091959.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":"1604-1623"},"PeriodicalIF":41.3,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148905223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}