CirculationPub Date : 2025-04-15Epub Date: 2025-03-19DOI: 10.1161/CIR.0000000000001308
Thomas D Ryan, James E Bates, Karen E Kinahan, Kasey J Leger, Daniel A Mulrooney, Hari K Narayan, Kirsten Ness, Tochukwu M Okwuosa, Nino C Rainusso, Julia Steinberger, Saro H Armenian
{"title":"Cardiovascular Toxicity in Patients Treated for Childhood Cancer: A Scientific Statement From the American Heart Association.","authors":"Thomas D Ryan, James E Bates, Karen E Kinahan, Kasey J Leger, Daniel A Mulrooney, Hari K Narayan, Kirsten Ness, Tochukwu M Okwuosa, Nino C Rainusso, Julia Steinberger, Saro H Armenian","doi":"10.1161/CIR.0000000000001308","DOIUrl":"10.1161/CIR.0000000000001308","url":null,"abstract":"<p><p>The field of cardio-oncology has expanded over the past 2 decades to address the ever-increasing issues related to cardiovascular disease in patients with cancer and survivors. There is increasing recognition that nearly all cancer treatments pose some short- or long-term risk for development of cardiovascular disease and that pediatric patients with cancer may be especially vulnerable to cardiovascular disease because of young age at treatment and expected long life span afterward. Anthracycline chemotherapy and chest-directed radiotherapy are the most well-studied cardiotoxic therapies, and dose reduction, use of cardioprotection for anthracyclines, and modern radiotherapy approaches have contributed to improved cardiovascular outcomes for survivors. Newer treatments such as small-molecule inhibitors, antibody-based cytotoxic therapy, and immunotherapy have expanded options for previously difficult-to-treat cancers but have also revealed new cardiotoxic profiles. Application of effective surveillance strategies in patients with cancer and survivors has been a focus of practitioners and researchers, whereas the prevention and treatment of extant cardiovascular disease is still developing. Incorporation of new strategies in an equitable manner and appropriate transition from pediatric to adult care will greatly influence long-term health-related outcomes in the growing population of childhood cancer survivors at risk for cardiovascular disease.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":"e926-e943"},"PeriodicalIF":35.5,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656249","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}
CirculationPub Date : 2025-04-14DOI: 10.1161/circulationaha.124.072253
Emmanuel Stamatakis,Raaj K Biswas,Nicholas A Koemel,Angelo Sabag,Richard Pulsford,Andrew J Atkin,Afroditi Stathi,Sonia Cheng,Cecilie Thøgersen-Ntoumani,Joanna M Blodgett,Adrian Bauman,Carlos Celis-Morales,Mark Hamer,Jason M R Gill,Matthew N Ahmadi
{"title":"Dose Response of Incidental Physical Activity Against Cardiovascular Events and Mortality.","authors":"Emmanuel Stamatakis,Raaj K Biswas,Nicholas A Koemel,Angelo Sabag,Richard Pulsford,Andrew J Atkin,Afroditi Stathi,Sonia Cheng,Cecilie Thøgersen-Ntoumani,Joanna M Blodgett,Adrian Bauman,Carlos Celis-Morales,Mark Hamer,Jason M R Gill,Matthew N Ahmadi","doi":"10.1161/circulationaha.124.072253","DOIUrl":"https://doi.org/10.1161/circulationaha.124.072253","url":null,"abstract":"BACKGROUNDFew middle-aged and older adults engage in regular leisure-time exercise. Incidental physical activity (IPA) encompasses activities of daily living outside the leisure-time domain. No dose-response study is available to guide IPA-focused interventions and guidelines. We examined the associations of device-assessed IPA intensities (vigorous [VIPA], moderate [MIPA], light [LIPA]) with major adverse cardiovascular events (MACE) and mortality, and we estimated the \"health equivalence\" of LIPA and MIPA against 1 minute of VIPA.METHODSA total of 24 139 nonexercisers from the 2013 to 2015 UK Biobank accelerometry substudy (56.2% women) with a mean±SD age of 61.9±7.6 years were analyzed using a prospective cohort design. IPA energy expenditure and daily durations of VIPA, MIPA, and LIPA were calculated with a validated machine learning-based intensity classifier. MACE included incident stroke, myocardial infarction, and heart failure; CVD death; CVD mortality; and all-cause mortality.RESULTSAnalyses included 22 107 (MACE), 22 174 (CVD mortality), and 24 139 (all-cause mortality) participants, corresponding to 908/223/1071 events over 7.9 years of follow-up. IPA volume exhibited an L-shaped association with a nadir at ≈35 to 38 kJ·kg-1·d-1, corresponding to hazard ratios of 0.49 (95% CI, 0.39-0.61) for MACE, 0.33 (95% CI, 0.22-0.52) for CVD mortality, and 0.31 (95% CI, 0.25-0.38) for all-cause mortality. Any amounts of VIPA or MIPA were associated with lower risk, with a plateau of ≈14 minutes per day (VIPA) and 34 to 50 minutes per day (MIPA). The median VIPA (4.6 min/d) and MIPA (23.8 min/d) durations were associated with CVD mortality hazard ratio of 0.62 (95% CI, 0.46-0.83) and 0.50 (95% CI, 0.31-0.80), respectively. LIPA showed a subtle inverse gradient which was statistically significant only for CVD mortality at levels >130 minutes per day. One minute of VIPA was equivalent to 2.8 (MACE) to 3.4 (CVD mortality) minutes of MIPA and 34.7 (CVD mortality) to 48.5 (MACE) minutes of LIPA.CONCLUSIONSAny daily IPA amount of vigorous or moderate intensity was associated with lower CVD risk in a dose-response manner. LIPA had weak associations with all outcomes. One minute of vigorous or ≈3.0 to 3.5 minutes of moderate IPA was associated with a similar degree of lower CVD risk. Our findings highlight the potential cardiovascular health value of incidental physical activity, especially for people who struggle to do structured exercise.","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"308 1","pages":"1063-1075"},"PeriodicalIF":37.8,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143836523","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}
CirculationPub Date : 2025-04-14DOI: 10.1161/circulationaha.125.073626
Nikolas Nozica,Usha Tedrow
{"title":"Assessing the Consequences of Retrograde and Transseptal Approaches to Ventricular Arrhythmia Ablation.","authors":"Nikolas Nozica,Usha Tedrow","doi":"10.1161/circulationaha.125.073626","DOIUrl":"https://doi.org/10.1161/circulationaha.125.073626","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"312 1","pages":"1060-1062"},"PeriodicalIF":37.8,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143836511","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}
CirculationPub Date : 2025-04-14DOI: 10.1161/circulationaha.124.071418
Xiaofeng Lu,Shaowen Liu,Songwen Chen
{"title":"Letter by Lu et al Regarding Article, \"Association of Atrial Fibrillation Burden and Mortality Among Patients With Cardiac Implantable Electronic Devices\".","authors":"Xiaofeng Lu,Shaowen Liu,Songwen Chen","doi":"10.1161/circulationaha.124.071418","DOIUrl":"https://doi.org/10.1161/circulationaha.124.071418","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"41 1","pages":"e923-e924"},"PeriodicalIF":37.8,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143836521","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":"Patient-Reported Outcomes as End Points in Heart Failure Trials.","authors":"Javed Butler,Muhammad Shariq Usman,Charu Gandotra,Ali Salman,Andrew Farb,Aliza M Thompson,Norman Stockbridge,Cordula Zeller,Folke Folkvaljon","doi":"10.1161/circulationaha.124.072158","DOIUrl":"https://doi.org/10.1161/circulationaha.124.072158","url":null,"abstract":"Heart failure is a growing health-care concern affecting tens of millions of individuals globally. Although traditional therapeutic strategies have focused on reducing the risk for hospitalization and mortality, the importance of patient-reported outcomes (PROs) in patients with heart failure is increasingly being recognized. Regulatory agencies consider PROs part of their evaluation of drugs and devices, and professional society guidelines may recommend interventions that improve PROs. However, for several reasons, the effect of interventions on PROs reported in heart failure trials currently is difficult to interpret. There is no consensus on the timing and frequency of PRO assessments. Moreover, it has been difficult to establish a minimal clinically important difference, that is, the minimal change in a PRO score that is meaningful to a patient. In addition, traditional methods of analyzing and reporting PROs such as comparison of mean differences across groups or responder analysis are prone to statistical artifacts and misinterpretation. This article presents an in-depth discussion of these issues, with the Kansas City Cardiomyopathy Questionnaire used as an example, to facilitate the use of PROs in heart failure research, regulatory, and clinical settings.","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"37 1","pages":"1111-1125"},"PeriodicalIF":37.8,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143836524","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}
CirculationPub Date : 2025-04-14DOI: 10.1161/circulationaha.124.072692
Graham Peigh,Sarah C Rosemas,Anthony I Roberts,Colleen Longacre,Rod S Passman
{"title":"Response by Peigh et al to Letter Regarding Article, \"Association of Atrial Fibrillation Burden and Mortality Among Patients With Cardiac Implantable Electronic Devices\".","authors":"Graham Peigh,Sarah C Rosemas,Anthony I Roberts,Colleen Longacre,Rod S Passman","doi":"10.1161/circulationaha.124.072692","DOIUrl":"https://doi.org/10.1161/circulationaha.124.072692","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"74 1","pages":"e925"},"PeriodicalIF":37.8,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143836545","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}
CirculationPub Date : 2025-04-14DOI: 10.1161/circulationaha.124.072958
Li Qian
{"title":"Reprogrammed Smooth Muscle Cells for Vascular Repair: A New Path to Healing Ischemic Tissue.","authors":"Li Qian","doi":"10.1161/circulationaha.124.072958","DOIUrl":"https://doi.org/10.1161/circulationaha.124.072958","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"9 1","pages":"1095-1097"},"PeriodicalIF":37.8,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143836544","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}
CirculationPub Date : 2025-04-11DOI: 10.1161/circulationaha.124.072340
Yan Zou,Jing Lu,Zhipeng Lian,Jianguo Jia,Juan Shen,Qianhe Li,Jennifer Ming Jen Wong,Kejia Jin,Wendi Yan,Xinyue Ren,Yang Zhang,Chenxing Huang,Huanjie Yang,Feng Huang,Jun Li,Junyu Zhai,Yamei Xu,Xialian Xu,Hang Yu,Yi Jin,Hui Gong,Jinzhong Lin,Junbo Ge,Yuxiang Dai
{"title":"Modified mRNA Treatment Restores Cardiac Function in Desmocollin-2-Deficient Mouse Models of Arrhythmogenic Right Ventricular Cardiomyopathy.","authors":"Yan Zou,Jing Lu,Zhipeng Lian,Jianguo Jia,Juan Shen,Qianhe Li,Jennifer Ming Jen Wong,Kejia Jin,Wendi Yan,Xinyue Ren,Yang Zhang,Chenxing Huang,Huanjie Yang,Feng Huang,Jun Li,Junyu Zhai,Yamei Xu,Xialian Xu,Hang Yu,Yi Jin,Hui Gong,Jinzhong Lin,Junbo Ge,Yuxiang Dai","doi":"10.1161/circulationaha.124.072340","DOIUrl":"https://doi.org/10.1161/circulationaha.124.072340","url":null,"abstract":"BACKGROUNDArrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited heart disease characterized by irregular rhythms and right ventricular dysplasia. Sequence variations in desmosomal protein-encoding genes are linked to ARVC development. Effective treatments for ARVC are lacking. Whereas mRNA-based therapies have shown efficacy in humans, their therapeutic potential for inherited cardiomyopathies remains unclear.METHODSWhole-exome sequencing identified a novel DSC2 sequence variation causing autosomal recessive ARVC in a Chinese family with consanguineous marriage. Mouse models with Dsc2 sequence variation knock-in and constitutive knock-out were generated and analyzed using echocardiography and histology. Transcriptomic and biochemical analyses were conducted to explore ARVC mechanisms. Dsc2 mRNA delivered by intracardiac or transcoronary injection was assessed as a treatment for ARVC in Dsc2 knock-out mice. In addition, effects of Dsc2 mRNA were examined in a transverse aortic constriction mouse model with noninherited right ventricular systolic dysfunction.RESULTSDsc2-deficient mice exhibited right ventricular dilation and dysfunction, mimicking human disease. Transcriptomic analysis identified Myl7 as the most downregulated gene in the right ventricles of Dsc2-deficient mice, and its restoration by adeno-associated virus 9 rescued heart function. Dsc2 mRNA delivery, with or without lipid nanoparticle encapsulation, normalized heart size and function in Dsc2-deficient mice. Reduced DSC2 and MLC2a expression was also noted in patients with noninherited dilated cardiomyopathy and in mice with transverse aortic constriction. A single dose of mRNA provided therapeutic effects lasting 2 to 3 months before declining.CONCLUSIONSOur study reveals novel mechanisms of ARVC caused by DSC2 loss of function, supported by human and mouse data. Loss of Myl7 contributes to reduced cardiac contractility in ARVC and dilated cardiomyopathy with right ventricular systolic dysfunction. Dsc2 mRNA treatment demonstrated significant therapeutic potential in ARVC and transverse aortic constriction models, providing a basis for future clinical applications.","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"25 1","pages":""},"PeriodicalIF":37.8,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143822554","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}
CirculationPub Date : 2025-04-10DOI: 10.1161/cir.0000000000001316
Kara M Whitaker,Bethany Barone Gibbs,Marie-France Hivert,Nour Makarem,Elizabeth Moxley,Jason Vaught,Kelly R Evenson,
{"title":"Sedentary Behavior and Light-Intensity Physical Activity During Pregnancy and Cardiovascular Health: A Science Advisory From the American Heart Association.","authors":"Kara M Whitaker,Bethany Barone Gibbs,Marie-France Hivert,Nour Makarem,Elizabeth Moxley,Jason Vaught,Kelly R Evenson,","doi":"10.1161/cir.0000000000001316","DOIUrl":"https://doi.org/10.1161/cir.0000000000001316","url":null,"abstract":"The Physical Activity Guidelines for Americans supports sitting less and moving more. Growing evidence suggests that a waking behavior profile with less sedentary behavior and more light-intensity physical activity is associated with more favorable cardiovascular health. Remarkably, little is known about how these behaviors relate to cardiovascular health during pregnancy. The purpose of this American Heart Association science advisory is to describe the existing evidence on device-measured sedentary behavior and light-intensity physical activity in relation to cardiovascular health during pregnancy and to make specific calls to action for future research to improve health outcomes and to promote health equity. Outcomes included adverse pregnancy outcomes associated with increased risk of cardiovascular disease and the American Heart Association's Life's Essential 8 health factor components (blood pressure, lipids, glucose, and gestational weight gain). Findings from observational studies are mixed, with preliminary evidence demonstrating an association between high sedentary behavior and increased risk of hypertensive disorders of pregnancy, shorter gestational age at delivery, low or high birth weight, and elevated maternal blood pressure, lipids, glucose, and gestational weight gain. Findings for light-intensity physical activity are limited by fewer studies and are less compelling. Experimental evidence evaluating the impact of decreasing sedentary behavior or increasing light-intensity physical activity on pregnancy cardiovascular health is weak. Future observational studies with rigorous longitudinal designs and larger, diverse samples are needed to characterize associations and to inform the design of adequately powered randomized controlled trials testing the impact of decreasing sedentary behavior and increasing light-intensity physical activity on cardiovascular health during pregnancy.","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"59 1","pages":""},"PeriodicalIF":37.8,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143819365","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}