Circulation最新文献

{"title":"Sustained but Decoyed Activation of the JAK1-STAT Pathway by Aberrant Protein Aggregation Exacerbates Proteotoxicity.","authors":"Mingqi Cai,Bo Pan,Peng Xiao,Mark Bouska,Megan T Lewno,Yu Xing,Erliang Zeng,Huiyun Liang,Faqian Li,Xiang Gao,Xuejun Wang","doi":"10.1161/circulationaha.124.070067","DOIUrl":"https://doi.org/10.1161/circulationaha.124.070067","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":null,"pages":null},"PeriodicalIF":37.8,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142439290","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":"Cardiac Arrhythmias and Autonomic Dysfunction Associated With COVID-19: A Scientific Statement From the American Heart Association.","authors":"Rakesh Gopinathannair,Brian Olshansky,Mina K Chung,Steve Gordon,Jose A Joglar,Gregory M Marcus,Philip L Mar,Andrea M Russo,Uma N Srivatsa,Elaine Y Wan,","doi":"10.1161/cir.0000000000001290","DOIUrl":"https://doi.org/10.1161/cir.0000000000001290","url":null,"abstract":"Cardiac arrhythmias are commonly noted in patients during infections with and recovery from COVID-19. Arrhythmic manifestations span the spectrum of innocuous and benign to life-threatening and deadly. Various pathophysiological mechanisms have been proposed. Debate continues on the impact of incident and exacerbated arrhythmias on the acute and chronic (recovery) phase of the illness. COVID-19 and COVID-19 vaccine-associated myocardial inflammation and autonomic disruption remain concerns. As the pandemic has transformed to an endemic, with discovery of new SARS-CoV-2 variants, updated vaccines, and potent antiviral drugs, vigilance for COVID-19-associated arrhythmic and dysautonomic manifestations remains. The objective of this American Heart Association scientific statement is to review the available evidence on the epidemiology, pathophysiology, clinical presentation, and management of cardiac arrhythmias and autonomic dysfunction in patients infected with and recovering from COVID-19 and to provide evidence-based guidance. The writing committee's consensus on implications for clinical practice, gaps in knowledge, and directions for future research are highlighted.","PeriodicalId":10331,"journal":{"name":"Circulation","volume":null,"pages":null},"PeriodicalIF":37.8,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142436040","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":"Muscle Mass and Glucagon-Like Peptide-1 Receptor Agonists: Adaptive or Maladaptive Response to Weight Loss?","authors":"Jennifer Linge,Andreas L Birkenfeld,Ian J Neeland","doi":"10.1161/circulationaha.124.067676","DOIUrl":"https://doi.org/10.1161/circulationaha.124.067676","url":null,"abstract":"Recent studies have shown that pharmacologic weight loss with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and combination therapies is approaching magnitudes achieved with surgery. However, as more weight loss is achieved, there is concern for potential adverse effects on muscle quantity, composition, and function. This primer aims to address whether muscle-related changes associated with weight loss treatments such as GLP-1 RAs may be maladaptive (ie, adversely affecting muscle health or function), adaptive (ie, a physiologic response to weight loss maintaining or minimally affecting muscle health or function), or perhaps an enhanced response to weight loss (ie, improved muscle health or function after treatment). Based on contemporary evidence with the addition of studies using magnetic resonance imaging, skeletal muscle changes with GLP-1 RA treatments appear to be adaptive: changes in muscle volume z-score indicate a change in muscle volume that is commensurate with what is expected given aging, disease status, and weight loss achieved, and the improvement in insulin sensitivity and muscle fat infiltration likely contributes to an adaptive process with improved muscle quality, lowering the probability for loss in strength and function. Nevertheless, factors such as older age and prefrailty may influence the selection of appropriate candidates for these therapies because of risk for sarcopenia. Several pharmacologic treatments to maintain or improve muscle mass designed in combination with GLP-1-based therapies are under development. For future development of GLP-1-based therapies (and other therapies) designed for weight loss, as well as for patient-centered treatment optimization, the introduction of more objective and comprehensive ways of assessing muscle health (including accurate and meaningful assessments of muscle quantity, composition, function, mobility, and strength) is important for the substantial numbers of patients who will likely be taking these medications well into the future.","PeriodicalId":10331,"journal":{"name":"Circulation","volume":null,"pages":null},"PeriodicalIF":37.8,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142439287","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":"Associations of Circulating ANGPTL3, C-Terminal Domain-Containing ANGPTL4, and ANGPTL3/8 and ANGPTL4/8 Complexes with LPL Activity, Diabetes, Inflammation, and Cardiovascular Mortality.","authors":"Günther Silbernagel, Yan Q Chen, Hongxia Li, Deven Lemen, Yi Wen, Eugene Y Zhen, Martin Rief, Marcus E Kleber, Graciela Delgado, Mark A Sarzynski, Yue-Wei Qian, Boerge Schmidt, Raimund Erbel, Ulrike Trampisch, Angela P Moissl, Henrik Rudolf, Heribert Schunkert, Andreas Stang, Winfried März, Hans J Trampisch, Hubert Scharnagl, Robert J Konrad","doi":"10.1161/CIRCULATIONAHA.124.069272","DOIUrl":"https://doi.org/10.1161/CIRCULATIONAHA.124.069272","url":null,"abstract":"<p><strong>Background: </strong>ANGPTL3/4/8 (angiopoietin-like proteins 3, 4, and 8) are important regulators of LPL (lipoprotein lipase). ANGPTL8 forms complexes with ANGPTL3 and ANGPTL4. ANGPTL4/8 complex formation converts ANGPTL4 from a furin substrate to a plasmin substrate, and both cleavages generate similar C-terminal domain-containing (CD)-ANGPTL4 fragments. Whereas several studies have investigated associations of free ANGPTL proteins with cardiovascular risk, there are no data describing associations of the complexes and CD-ANGPTL4 with outcomes or describing the effects of the complexes on LPL bound to GPIHBP1 (glycosylphosphatidylinositol HDL-binding protein 1).</p><p><strong>Methods: </strong>Recombinant protein assays were used to study ANGPTL protein and complex effects on GPIHBP1-LPL activity. ANGPTL3/8, ANGPTL3, ANGPTL4/8, and CD-ANGPTL4 were measured with dedicated immunoassays in 2394 LURIC (Ludwigshafen Risk and Cardiovascular Health) study participants undergoing coronary angiography and 6188 getABI study (German Epidemiological Trial on Ankle Brachial Index) participants undergoing ankle brachial index measurement. There was a follow-up for cardiovascular death with a median (interquartile range) duration of 9.80 (8.75-10.40) years in the LURIC study and 7.06 (7.00-7.14) years in the getABI study.</p><p><strong>Results: </strong>ANGPTL3/8 potently inhibited GPIHBP1-LPL activity and showed positive associations with LDL-C (low-density lipoprotein cholesterol) and triglycerides (both <i>P</i><0.001). However, in neither study did ANGPTL3/8 correlate with cardiovascular death. Free ANGPTL3 was positively associated with cardiovascular death in the getABI study but not the LURIC study. ANGPTL4/8 and especially CD-ANGPTL4 were positively associated with the prevalence of diabetes, CRP (C-reactive protein; all <i>P</i><0.001), and cardiovascular death in both studies. In the LURIC and getABI studies, respective hazard ratios for cardiovascular mortality comparing the third with the first ANGPTL4/8 tertile were 1.47 (1.15-1.88) and 1.68 (1.25-2.27) when adjusted for sex, age, body mass index, and diabetes. For CD-ANGPTL4, these hazard ratios were 2.44 (1.86-3.20) and 2.76 (2.00-3.82).</p><p><strong>Conclusions: </strong>ANGPTL3/8 potently inhibited GPIHBP1-LPL enzymatic activity, consistent with its positive association with serum lipids. However, ANGPTL3/8, LDL-C, and triglyceride levels were not associated with cardiovascular death in the LURIC and getABI cohorts. In contrast, concentrations of ANGPTL4/8 and particularly CD-ANGPTL4 were positively associated with inflammation, the prevalence of diabetes, and cardiovascular mortality.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":null,"pages":null},"PeriodicalIF":35.5,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399592","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":"A Rare Noncoding Enhancer Variant in <i>SCN5A</i> Contributes to the High Prevalence of Brugada Syndrome in Thailand.","authors":"Roddy Walsh, John Mauleekoonphairoj, Isabella Mengarelli, Fernanda M Bosada, Arie O Verkerk, Karel van Duijvenboden, Yong Poovorawan, Wanwarang Wongcharoen, Boosamas Sutjaporn, Pharawee Wandee, Nitinan Chimparlee, Ronpichai Chokesuwattanaskul, Kornkiat Vongpaisarnsin, Piyawan Dangkao, Cheng-I Wu, Rafik Tadros, Ahmad S Amin, Krystien V V Lieve, Pieter G Postema, Maarten Kooyman, Leander Beekman, Dujdao Sahasatas, Montawatt Amnueypol, Rungroj Krittayaphong, Somchai Prechawat, Alisara Anannab, Pattarapong Makarawate, Tachapong Ngarmukos, Keerapa Phusanti, Gumpanart Veerakul, Zoya Kingsbury, Taksina Newington, Uma Maheswari, Mark T Ross, Andrew Grace, Pier D Lambiase, Elijah R Behr, Jean-Jacques Schott, Richard Redon, Julien Barc, Vincent M Christoffels, Arthur A M Wilde, Koonlawee Nademanee, Connie R Bezzina, Apichai Khongphatthanayothin","doi":"10.1161/CIRCULATIONAHA.124.069041","DOIUrl":"https://doi.org/10.1161/CIRCULATIONAHA.124.069041","url":null,"abstract":"<p><strong>Background: </strong>Brugada syndrome (BrS) is a cardiac arrhythmia disorder that causes sudden death in young adults. Rare genetic variants in the <i>SCN5A</i> gene encoding the Na_v1.5 sodium channel and common noncoding variants at this locus are robustly associated with the condition. BrS is particularly prevalent in Southeast Asia but the underlying ancestry-specific factors remain largely unknown.</p><p><strong>Methods: </strong>Genome sequencing of BrS probands and population-matched controls from Thailand was performed to identify rare noncoding variants at the <i>SCN5A-SCN10A</i> locus that were enriched in patients with BrS. A likely causal variant was prioritized by computational methods and introduced into human induced pluripotent stem cell (hiPSC) lines using CRISPR-Cas9. The effect of the variant on <i>SCN5A</i> expression and Na_v1.5 sodium channel current was then assessed in hiPSC-derived cardiomyocytes (hiPSC-CMs).</p><p><strong>Results: </strong>A rare noncoding variant in an <i>SCN5A</i> intronic enhancer region was highly enriched in patients with BrS (detected in 3.9% of cases with a case-control odds ratio of 45.2). The variant affects a nucleotide conserved across all mammalian species and predicted to disrupt a Mef2 transcription factor binding site. Heterozygous introduction of the enhancer variant in hiPSC-CMs caused significantly reduced <i>SCN5A</i> expression from the variant-containing allele and a 30% reduction in Na_v1.5-mediated sodium current density compared with isogenic controls, confirming its pathogenicity. Patients with the variant had severe phenotypes, with 89% experiencing cardiac arrest.</p><p><strong>Conclusions: </strong>This is the first example of a functionally validated rare noncoding variant at the <i>SCN5A</i> locus and highlights how genome sequencing in understudied populations can identify novel disease mechanisms. The variant partly explains the increased prevalence of BrS in this region and enables the identification of at-risk variant carriers to reduce the burden of sudden cardiac death in Thailand.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":null,"pages":null},"PeriodicalIF":35.5,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399591","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":"YAP Overcomes Mechanical Barriers to Induce Mitotic Rounding and Adult Cardiomyocyte Division.","authors":"Yuka Morikawa, Jong H Kim, Rich Gang Li, Lin Liu, Shijie Liu, Vaibhav Deshmukh, Matthew C Hill, James F Martin","doi":"10.1161/CIRCULATIONAHA.123.066004","DOIUrl":"https://doi.org/10.1161/CIRCULATIONAHA.123.066004","url":null,"abstract":"<p><strong>Background: </strong>Many specialized cells in adult organs acquire a state of cell cycle arrest and quiescence through unknown mechanisms. Our limited understanding of mammalian cell cycle arrest is derived primarily from cell culture models. Adult mammalian cardiomyocytes, a classic example of cell cycle arrested cells, exit the cell cycle postnatally and remain in an arrested state for the life of the organism. Cardiomyocytes can be induced to re-enter the cell cycle by YAP5SA, an active form of the Hippo signaling pathway effector YAP.</p><p><strong>Methods: </strong>We performed clonal analyses to determine the cell kinetics of YAP5SA cardiomyocytes. We also performed single-cell RNA sequencing, marker gene analysis, and functional studies to examine how YAP5SA cardiomyocytes progress through the cell cycle.</p><p><strong>Results: </strong>We discovered that YAP5SA-expressing cardiomyocytes divided efficiently, with >20% of YAP5SA cardiomyocyte clones containing ≥2 cardiomyocytes. YAP5SA cardiomyocytes re-entered cell cycle at the G1/S transition and had an S phase lasting ≈48 hours. Sarcomere disassembly is required for cardiomyocyte progression from S to G2 phase and the induction of mitotic rounding. Although oscillatory Cdk expression was induced in YAP5SA cardiomyocytes, these cells inefficiently progressed through G2 phase. This is improved by inhibiting P21 function, implicating checkpoint activity as an additional barrier to YAP5SA-induced cardiomyocyte division.</p><p><strong>Conclusions: </strong>Our data reveal that YAP5SA overcomes the mechanically constrained myocardial microenvironment to induce mitotic rounding with cardiomyocyte division, thus providing new insights into the in vivo mechanisms that maintain cell cycle quiescence in adult mammals.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":null,"pages":null},"PeriodicalIF":35.5,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399594","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":"Optimizing AHA/ACC Guidelines for the Digital Age: Guidelines in Evolution.","authors":"Catherine M Otto, Mariell Jessup, Richard J Kovacs, Joshua A Beckman","doi":"10.1161/CIR.0000000000001294","DOIUrl":"https://doi.org/10.1161/CIR.0000000000001294","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":null,"pages":null},"PeriodicalIF":35.5,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399593","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":"Antisense Oligonucleotide Therapy for Calmodulinopathy.","authors":"Raul H Bortolin, Farina Nawar, Chaehyoung Park, Michael A Trembley, Maksymilian Prondzynski, Mason E Sweat, Peizhe Wang, Jiehui Chen, Fujian Lu, Carter Liou, Paul Berkson, Erin M Keating, Daisuke Yoshinaga, Nikoleta Pavlaki, Thomas Samenuk, Cecilia B Cavazzoni, Peter T Sage, Qing Ma, Robert D Whitehill, Dominic J Abrams, Chrystalle Katte Carreon, Juan Putra, Sanda Alexandrescu, Shuai Guo, Wen-Chin Tsai, Michael Rubart, Dieter A Kubli, Adam E Mullick, Vassilios J Bezzerides, William T Pu","doi":"10.1161/CIRCULATIONAHA.123.068111","DOIUrl":"10.1161/CIRCULATIONAHA.123.068111","url":null,"abstract":"<p><strong>Background: </strong>Calmodulinopathies are rare inherited arrhythmia syndromes caused by dominant heterozygous variants in <i>CALM1</i>, <i>CALM2</i>, or <i>CALM3</i>, which each encode the identical CaM (calmodulin) protein. We hypothesized that antisense oligonucleotide (ASO)-mediated depletion of an affected calmodulin gene would ameliorate disease manifestations, whereas the other 2 calmodulin genes would preserve CaM level and function.</p><p><strong>Methods: </strong>We tested this hypothesis using human induced pluripotent stem cell-derived cardiomyocyte and mouse models of <i>CALM1</i> pathogenic variants.</p><p><strong>Results: </strong>Human <i>CALM1</i>^{<i>F142L/+</i>} induced pluripotent stem cell-derived cardiomyocytes exhibited prolonged action potentials, modeling congenital long QT syndrome. CALM1 knockout or CALM1-depleting ASOs did not alter CaM protein level and normalized repolarization duration of <i>CALM1</i>^{<i>F142L/+</i>} induced pluripotent stem cell-derived cardiomyocytes. Similarly, an ASO targeting murine <i>Calm1</i> depleted <i>Calm1</i> transcript without affecting CaM protein level. This ASO alleviated drug-induced bidirectional ventricular tachycardia in <i>Calm1</i>^{<i>N98S/+</i>} mice without a deleterious effect on cardiac electrical or contractile function.</p><p><strong>Conclusions: </strong>These results provide proof of concept that ASOs targeting individual calmodulin genes are potentially effective and safe therapies for calmodulinopathies.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":null,"pages":null},"PeriodicalIF":35.5,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141999494","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":"All That Is Gold Does Not Glitter.","authors":"Andrew M Luks, Benjamin D Levine","doi":"10.1161/CIRCULATIONAHA.124.069723","DOIUrl":"https://doi.org/10.1161/CIRCULATIONAHA.124.069723","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":null,"pages":null},"PeriodicalIF":35.5,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388526","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":"Long-Term Incidence of Bradycardia and Pacemaker Implantations Among Cross-Country Skiers: A Cohort Study.","authors":"Niclas Svedberg, Johan Sundström, Stefan James, Ulf Hållmarker, Kristina Hambraeus, Kasper Andersen","doi":"10.1161/CIRCULATIONAHA.123.068280","DOIUrl":"10.1161/CIRCULATIONAHA.123.068280","url":null,"abstract":"<p><strong>Background: </strong>Bradycardia is more common among well-trained athletes than in the general population, but the association with pacemaker implantations is less known. We investigated associations of endurance training with incidence of bradycardia and pacemaker implantations, including sex differences and long-term outcome, in a cohort of endurance trained individuals.</p><p><strong>Methods: </strong>All Swedish skiers who completed >1 race in the cross-country skiing event Vasaloppet between 1989 and 2011 (n=209 108) and a sample of 532 290 nonskiers were followed until first event of bradycardia, pacemaker implantation, or death, depending on end point. The Swedish National Patient Register was used to obtain diagnoses. Cox regression was used to investigate associations of number of completed races and finishing time in Vasaloppet with incidence of bradycardia and pacemaker implantations. In addition, Cox regression was used to investigate associations of pacemaker implantations with death in skiers and nonskiers.</p><p><strong>Results: </strong>Male skiers had a higher incidence of bradycardia (adjusted hazard ratio [aHR], 1.19 [95% CI, 1.05-1.34]) and pacemaker implantations (aHR, 1.17 [95% CI, 1.04-1.31]) compared with male nonskiers. Those who completed the most races and had the best performances exhibited the highest incidence. For female skiers in Vasaloppet, the incidence of bradycardia (aHR, 0.98 [95% CI, 0.75-1.30]) and pacemaker implantations (aHR, 0.98 [95% CI, 0.75-1.29]) was not different from that of female nonskiers. The indication for pacemaker differed between skiers and nonskiers, with sick sinus syndrome more common in the former and third-degree atrioventricular block in the latter. Skiers had lower overall mortality rates than nonskiers (aHR, 0.16 [95% CI, 0.15-0.17]). There were no differences in mortality rates by pacemaker status among skiers.</p><p><strong>Conclusions: </strong>In this study, male endurance skiers had a higher incidence of bradycardia and pacemaker implantations compared with nonskiers, a pattern not seen in women. Among male skiers, those who completed the most races and had the fastest finishing times had the highest incidence of bradycardia and pacemaker implantations. Within each group, mortality rates did not differ in relation to pacemaker status. These findings suggest that bradycardia associated with training leads to a higher risk for pacemaker implantation without a detrimental effect on mortality risk.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":null,"pages":null},"PeriodicalIF":35.5,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141888676","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}