Pub Date : 2024-12-10Epub Date: 2024-12-09DOI: 10.1161/CIRCULATIONAHA.124.070337
Megan C Lancaster, Giovanni Davogustto, Edi Prifti, Claire Perret, Christian Funck-Brentano, Dan M Roden, Joe-Elie Salem
{"title":"A Polygenic Predictor of Baseline QTc is Associated With Sotalol-Induced QT Prolongation.","authors":"Megan C Lancaster, Giovanni Davogustto, Edi Prifti, Claire Perret, Christian Funck-Brentano, Dan M Roden, Joe-Elie Salem","doi":"10.1161/CIRCULATIONAHA.124.070337","DOIUrl":"https://doi.org/10.1161/CIRCULATIONAHA.124.070337","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"150 24","pages":"1984-1986"},"PeriodicalIF":35.5,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142799494","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}
Pub Date : 2024-12-10DOI: 10.1161/CIRCULATIONAHA.124.070563
Bo Sun, Mingke Ni, Yanhui Li, Zhenpeng Song, Hui Wang, Hai-Lei Zhu, Jinhong Wei, Darrell Belke, Shitian Cai, Wenting Guo, Jinjing Yao, Shanshan Tian, John Paul Estillore, Ruiwu Wang, Mads Toft Sondergaard, Malene Brohus, Palle Duun Rohde, Yongxin Mu, Alexander Vallmitjana, Raul Benitez, Leif Hove-Madsen, Michael Toft Overgaard, Glenn I Fishman, Ju Chen, Shubhayan Sanatani, Arthur A M Wilde, Michael Fill, Josefina Ramos-Franco, Mette Nyegaard, S R Wayne Chen
Background: Ca2+ mishandling in cardiac Purkinje cells is a well-known cause of cardiac arrhythmias. The Purkinje cell resident inositol 1,4,5-trisphosphate receptor 1 (ITPR1) is believed to play an important role in Ca2+ handling, and ITPR1 gain-of-function (GOF) has been implicated in cardiac arrhythmias. However, nearly all known disease-associated ITPR1 variants are loss-of-function and are primarily linked to neurological disorders. Whether ITPR1 GOF has pathological consequences, such as cardiac arrhythmias, is unclear. This study aimed to identify human ITPR1 GOF variants and determine the impact of ITPR1 GOF on Ca2+ handling and arrhythmia susceptibility.
Methods: There are a large number of rare ITPR1 missense variants reported in open data repositories. Based on their locations in the ITPR1 channel structure, we selected and characterized 33 human ITPR1 missense variants from open databases and identified 21 human ITPR1 GOF variants. We generated a mouse model carrying a human ITPR1 GOF variant, ITPR1-W1457G (W1447G in mice).
Results: We showed that the ITPR1-W1447G± and recently reported ITPR1-D2594K± GOF mutant mice were susceptible to stress-induced ventricular arrhythmias. Confocal Ca2+ and voltage imaging in situ in heart slices and Ca2+ imaging and patch-clamp recordings of isolated Purkinje cells showed that ITPR1-W1447G± and ITPR1-D2594K± variants increased the occurrence of stress-induced spontaneous Ca2+ release, delayed afterdepolarization, and triggered activity in Purkinje cells. To assess the potential role of ITPR1 variants in arrhythmia susceptibility in humans, we looked up a gene-based association study in the UK Biobank data set and identified 7 rare ITPR1 missense variants showing potential association with cardiac arrhythmias. Remarkably, in vitro functional characterization revealed that all these 7 ITPR1 variants resulted in GOF.
Conclusions: Our studies in mice and humans reveal that enhanced function of ITPR1, a well-known movement disorder gene, increases the risk for cardiac arrhythmias.
{"title":"Inositol 1,4,5-Trisphosphate Receptor 1 Gain-of-Function Increases the Risk for Cardiac Arrhythmias in Mice and Humans.","authors":"Bo Sun, Mingke Ni, Yanhui Li, Zhenpeng Song, Hui Wang, Hai-Lei Zhu, Jinhong Wei, Darrell Belke, Shitian Cai, Wenting Guo, Jinjing Yao, Shanshan Tian, John Paul Estillore, Ruiwu Wang, Mads Toft Sondergaard, Malene Brohus, Palle Duun Rohde, Yongxin Mu, Alexander Vallmitjana, Raul Benitez, Leif Hove-Madsen, Michael Toft Overgaard, Glenn I Fishman, Ju Chen, Shubhayan Sanatani, Arthur A M Wilde, Michael Fill, Josefina Ramos-Franco, Mette Nyegaard, S R Wayne Chen","doi":"10.1161/CIRCULATIONAHA.124.070563","DOIUrl":"https://doi.org/10.1161/CIRCULATIONAHA.124.070563","url":null,"abstract":"<p><strong>Background: </strong>Ca<sup>2+</sup> mishandling in cardiac Purkinje cells is a well-known cause of cardiac arrhythmias. The Purkinje cell resident inositol 1,4,5-trisphosphate receptor 1 (ITPR1) is believed to play an important role in Ca<sup>2+</sup> handling, and ITPR1 gain-of-function (GOF) has been implicated in cardiac arrhythmias. However, nearly all known disease-associated ITPR1 variants are loss-of-function and are primarily linked to neurological disorders. Whether ITPR1 GOF has pathological consequences, such as cardiac arrhythmias, is unclear. This study aimed to identify human ITPR1 GOF variants and determine the impact of ITPR1 GOF on Ca<sup>2+</sup> handling and arrhythmia susceptibility.</p><p><strong>Methods: </strong>There are a large number of rare ITPR1 missense variants reported in open data repositories. Based on their locations in the ITPR1 channel structure, we selected and characterized 33 human ITPR1 missense variants from open databases and identified 21 human ITPR1 GOF variants. We generated a mouse model carrying a human ITPR1 GOF variant, ITPR1-W1457G (W1447G in mice).</p><p><strong>Results: </strong>We showed that the ITPR1-W1447G<sup>±</sup> and recently reported ITPR1-D2594K<sup>±</sup> GOF mutant mice were susceptible to stress-induced ventricular arrhythmias. Confocal Ca<sup>2+</sup> and voltage imaging in situ in heart slices and Ca<sup>2+</sup> imaging and patch-clamp recordings of isolated Purkinje cells showed that ITPR1-W1447G<sup>±</sup> and ITPR1-D2594K<sup>±</sup> variants increased the occurrence of stress-induced spontaneous Ca<sup>2+</sup> release, delayed afterdepolarization, and triggered activity in Purkinje cells. To assess the potential role of ITPR1 variants in arrhythmia susceptibility in humans, we looked up a gene-based association study in the UK Biobank data set and identified 7 rare ITPR1 missense variants showing potential association with cardiac arrhythmias. Remarkably, in vitro functional characterization revealed that all these 7 ITPR1 variants resulted in GOF.</p><p><strong>Conclusions: </strong>Our studies in mice and humans reveal that enhanced function of ITPR1, a well-known movement disorder gene, increases the risk for cardiac arrhythmias.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":""},"PeriodicalIF":35.5,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142799421","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}
Pub Date : 2024-12-10DOI: 10.1161/CIRCULATIONAHA.124.071777
Seiko N Doi, Jawad H Butt, Jens Jakob Thune, Jens C Nielsen, Jens Haarbo, Niels E Bruun, Line L Olesen, Lars Videbæk, Finn Gustafsson, Hans Eiskjær, Christian Hassager, Jesper H Svendsen, Dan E Høfsten, Steen Pehrson, Lars Køber
{"title":"Left Ventricular Ejection Fraction and Implantable Cardioverter-Defibrillator in Non-ischemic Heart Failure with Reduced Ejection Fraction: Insights from DANISH.","authors":"Seiko N Doi, Jawad H Butt, Jens Jakob Thune, Jens C Nielsen, Jens Haarbo, Niels E Bruun, Line L Olesen, Lars Videbæk, Finn Gustafsson, Hans Eiskjær, Christian Hassager, Jesper H Svendsen, Dan E Høfsten, Steen Pehrson, Lars Køber","doi":"10.1161/CIRCULATIONAHA.124.071777","DOIUrl":"https://doi.org/10.1161/CIRCULATIONAHA.124.071777","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":""},"PeriodicalIF":35.5,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142806350","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}
Pub Date : 2024-12-10Epub Date: 2024-12-09DOI: 10.1161/CIRCULATIONAHA.124.072449
Adam J Lewandowski, Martin K Rutter, Rory Collins
{"title":"Scientific and Clinical Impacts of UK Biobank in Cardiovascular Medicine.","authors":"Adam J Lewandowski, Martin K Rutter, Rory Collins","doi":"10.1161/CIRCULATIONAHA.124.072449","DOIUrl":"https://doi.org/10.1161/CIRCULATIONAHA.124.072449","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"150 24","pages":"1907-1909"},"PeriodicalIF":35.5,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142799439","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}
Pub Date : 2024-12-10Epub Date: 2024-12-09DOI: 10.1161/CIRCULATIONAHA.124.070427
Huixin Huang, Xuqi Yang, Kai Yang
{"title":"Letter by Huang et al Regarding Article, \"Atherosclerosis Is a Smooth Muscle Cell-Driven Tumor-Like Disease\".","authors":"Huixin Huang, Xuqi Yang, Kai Yang","doi":"10.1161/CIRCULATIONAHA.124.070427","DOIUrl":"https://doi.org/10.1161/CIRCULATIONAHA.124.070427","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"150 24","pages":"e517-e518"},"PeriodicalIF":35.5,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142799433","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}
Pub Date : 2024-12-10Epub Date: 2024-12-09DOI: 10.1161/CIRCULATIONAHA.124.072220
Jesús Álvarez-García
{"title":"Cognitive Dysfunction in Heart Failure With Preserved Ejection Fraction: Uncovering the Consequences of an Overlooked Comorbidity.","authors":"Jesús Álvarez-García","doi":"10.1161/CIRCULATIONAHA.124.072220","DOIUrl":"https://doi.org/10.1161/CIRCULATIONAHA.124.072220","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"150 24","pages":"1928-1930"},"PeriodicalIF":35.5,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142799506","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}
Pub Date : 2024-12-05DOI: 10.1161/CIRCULATIONAHA.124.069398
Joshua K Meisner, Aaron Renberg, Eric D Smith, Yao-Chang Tsan, Brynn Elder, Abbey Bullard, Owen Merritt, Sean L Zheng, Neal Lakdawala, Anjali Owens, Thomas D Ryan, Erin M Miller, Joseph Rossano, Kimberly Y Lin, Brian Claggett, Euan Ashley, Michelle Michels, Rachel Lampert, John C Stendahl, Dominic Abrahams, Christopher Semsarian, Victoria N Parikh, Matthew Wheeler, Jodie Ingles, Sharlene M Day, Sara Saberi, Mark W Russell, Michael Previs, Carolyn Ho, James S Ware, Adam S Helms
Background: Classically, hypertrophic cardiomyopathy (HCM) has been viewed as a single-gene (monogenic) disease caused by pathogenic variants in sarcomere genes. Pathogenic sarcomere variants are individually rare and convey high risk for developing HCM (highly penetrant). Recently, important polygenic contributions have also been characterized. Low penetrance sarcomere variants (LowSVs) at intermediate frequencies and effect sizes have not been systematically investigated. We hypothesize that LowSVs may be common in HCM with substantial influence on disease risk and severity.
Methods: Among all sarcomere variants observed in the Sarcomeric Human Cardiomyopathy Registry (SHaRe), we identified putative LowSVs defined by (1) population frequency greater than expected for highly penetrant (monogenic) HCM (allele frequency >5×10-5 in the Genome Aggregation Database, gnomAD) and (2) moderate enrichment (>2×) in patients with HCM compared with gnomAD. LowSVs were examined for their association with disease severity and clinical outcomes. Functional effects of selected LowSVs were assessed using induced pluripotent stem cell-derived cardiomyocytes. Association of LowSVs with HCM-adjacent traits in the general population was tested using UK Biobank cardiac magnetic resonance imaging data.
Results: Among 6045 patients and 1159 unique variants in sarcomere genes, 12 LowSVs were identified. LowSVs were collectively common in the general population (1:350) and moderately enriched in HCM (aggregate odds ratio, 14.9 [95% CI, 12.5-17.9]). Isolated LowSVs were associated with an older age of HCM diagnosis and fewer adverse events. However, LowSVs in combination with a pathogenic sarcomere variant conferred higher morbidity (eg, composite adverse event hazard ratio, 5.4 [95% CI, 3.0-9.8] versus single pathogenic sarcomere variant, 2.0 [95% CI, 1.8-2.2]; P<0.001). An intermediate functional impact was validated for 2 specific LowSVs-MYBPC3 c.442G>A (partial splice gain) and TNNT2 c.832C>T (intermediate effect on contractile mechanics). Cardiac magnetic resonance imaging analysis of the general population revealed 5 of 12 LowSVs were significantly associated with HCM-adjacent traits without overt HCM.
Conclusions: This study establishes a new class of low penetrance sarcomere variants that are relatively common in the population. When penetrant, isolated LowSVs cause mild HCM. In combination with pathogenic sarcomere variants, LowSVs markedly increase disease severity, supporting a clinically significant additive effect. Last, LowSVs also contribute to age-related remodeling even in the absence of overt HCM.
{"title":"Low Penetrance Sarcomere Variants Contribute to Additive Risk in Hypertrophic Cardiomyopathy.","authors":"Joshua K Meisner, Aaron Renberg, Eric D Smith, Yao-Chang Tsan, Brynn Elder, Abbey Bullard, Owen Merritt, Sean L Zheng, Neal Lakdawala, Anjali Owens, Thomas D Ryan, Erin M Miller, Joseph Rossano, Kimberly Y Lin, Brian Claggett, Euan Ashley, Michelle Michels, Rachel Lampert, John C Stendahl, Dominic Abrahams, Christopher Semsarian, Victoria N Parikh, Matthew Wheeler, Jodie Ingles, Sharlene M Day, Sara Saberi, Mark W Russell, Michael Previs, Carolyn Ho, James S Ware, Adam S Helms","doi":"10.1161/CIRCULATIONAHA.124.069398","DOIUrl":"https://doi.org/10.1161/CIRCULATIONAHA.124.069398","url":null,"abstract":"<p><strong>Background: </strong>Classically, hypertrophic cardiomyopathy (HCM) has been viewed as a single-gene (monogenic) disease caused by pathogenic variants in sarcomere genes. Pathogenic sarcomere variants are individually rare and convey high risk for developing HCM (highly penetrant). Recently, important polygenic contributions have also been characterized. Low penetrance sarcomere variants (LowSVs) at intermediate frequencies and effect sizes have not been systematically investigated. We hypothesize that LowSVs may be common in HCM with substantial influence on disease risk and severity.</p><p><strong>Methods: </strong>Among all sarcomere variants observed in the Sarcomeric Human Cardiomyopathy Registry (SHaRe), we identified putative LowSVs defined by (1) population frequency greater than expected for highly penetrant (monogenic) HCM (allele frequency >5×10<sup>-5</sup> in the Genome Aggregation Database, gnomAD) and (2) moderate enrichment (>2×) in patients with HCM compared with gnomAD. LowSVs were examined for their association with disease severity and clinical outcomes. Functional effects of selected LowSVs were assessed using induced pluripotent stem cell-derived cardiomyocytes. Association of LowSVs with HCM-adjacent traits in the general population was tested using UK Biobank cardiac magnetic resonance imaging data.</p><p><strong>Results: </strong>Among 6045 patients and 1159 unique variants in sarcomere genes, 12 LowSVs were identified. LowSVs were collectively common in the general population (1:350) and moderately enriched in HCM (aggregate odds ratio, 14.9 [95% CI, 12.5-17.9]). Isolated LowSVs were associated with an older age of HCM diagnosis and fewer adverse events. However, LowSVs in combination with a pathogenic sarcomere variant conferred higher morbidity (eg, composite adverse event hazard ratio, 5.4 [95% CI, 3.0-9.8] versus single pathogenic sarcomere variant, 2.0 [95% CI, 1.8-2.2]; <i>P</i><0.001). An intermediate functional impact was validated for 2 specific LowSVs-<i>MYBPC3</i> c.442G>A (partial splice gain) and <i>TNNT2</i> c.832C>T (intermediate effect on contractile mechanics). Cardiac magnetic resonance imaging analysis of the general population revealed 5 of 12 LowSVs were significantly associated with HCM-adjacent traits without overt HCM.</p><p><strong>Conclusions: </strong>This study establishes a new class of low penetrance sarcomere variants that are relatively common in the population. When penetrant, isolated LowSVs cause mild HCM. In combination with pathogenic sarcomere variants, LowSVs markedly increase disease severity, supporting a clinically significant additive effect. Last, LowSVs also contribute to age-related remodeling even in the absence of overt HCM.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":""},"PeriodicalIF":35.5,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142779449","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}
Pub Date : 2024-12-03Epub Date: 2024-11-11DOI: 10.1161/CIR.0000000000001296
Yuri Kim, Andrew P Landstrom, Svati H Shah, Joseph C Wu, Christine E Seidman
Cardiovascular disease remains the foremost cause of morbidity and mortality globally, affecting millions of individuals. Recent discoveries illuminate the substantial role of genetics in cardiovascular disease pathogenesis, encompassing both monogenic and polygenic mechanisms and identifying tangible targets for gene therapies. Innovative strategies have emerged to rectify pathogenic variants that cause monogenic disorders such as hypertrophic, dilated, and arrhythmogenic cardiomyopathies and hypercholesterolemia. These include delivery of exogenous genes to supplement insufficient protein levels caused by pathogenic variants or genome editing to correct, delete, or modify mutant sequences to restore protein function. However, effective delivery of gene therapy to specified cells presents formidable challenges. Viral vectors, notably adeno-associated viruses and nonviral vectors such as lipid and engineered nanoparticles, offer distinct advantages and limitations. Additional risks and obstacles remain, including treatment durability, tissue-specific targeting, vector-associated adverse events, and off-target effects. Addressing these challenges is an ongoing imperative; several clinical gene therapy trials are underway, and many more first-in-human studies are anticipated. This science advisory reviews core concepts of gene therapy, key obstacles, patient risks, and ongoing research endeavors to enable clinicians to understand the complex landscape of this emerging therapy and its remarkable therapeutic potential to benefit cardiovascular disease.
{"title":"Gene Therapy in Cardiovascular Disease: Recent Advances and Future Directions in Science: A Science Advisory From the American Heart Association.","authors":"Yuri Kim, Andrew P Landstrom, Svati H Shah, Joseph C Wu, Christine E Seidman","doi":"10.1161/CIR.0000000000001296","DOIUrl":"10.1161/CIR.0000000000001296","url":null,"abstract":"<p><p>Cardiovascular disease remains the foremost cause of morbidity and mortality globally, affecting millions of individuals. Recent discoveries illuminate the substantial role of genetics in cardiovascular disease pathogenesis, encompassing both monogenic and polygenic mechanisms and identifying tangible targets for gene therapies. Innovative strategies have emerged to rectify pathogenic variants that cause monogenic disorders such as hypertrophic, dilated, and arrhythmogenic cardiomyopathies and hypercholesterolemia. These include delivery of exogenous genes to supplement insufficient protein levels caused by pathogenic variants or genome editing to correct, delete, or modify mutant sequences to restore protein function. However, effective delivery of gene therapy to specified cells presents formidable challenges. Viral vectors, notably adeno-associated viruses and nonviral vectors such as lipid and engineered nanoparticles, offer distinct advantages and limitations. Additional risks and obstacles remain, including treatment durability, tissue-specific targeting, vector-associated adverse events, and off-target effects. Addressing these challenges is an ongoing imperative; several clinical gene therapy trials are underway, and many more first-in-human studies are anticipated. This science advisory reviews core concepts of gene therapy, key obstacles, patient risks, and ongoing research endeavors to enable clinicians to understand the complex landscape of this emerging therapy and its remarkable therapeutic potential to benefit cardiovascular disease.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":"e471-e480"},"PeriodicalIF":35.5,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142615903","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}
Pub Date : 2024-12-03Epub Date: 2024-11-13DOI: 10.1161/CIR.0000000000001295
Pei-Ni Jone, Adriana Tremoulet, Nadine Choueiter, Samuel R Dominguez, Ashraf S Harahsheh, Yoshihide Mitani, Meghan Zimmerman, Ming-Tai Lin, Kevin G Friedman
Kawasaki disease (KD), an acute self-limited febrile illness that primarily affects children <5 years old, is the leading cause of acquired heart disease in developed countries, with the potential of leading to coronary artery dilation and coronary artery aneurysms in 25% of untreated patients. This update summarizes relevant clinical data published since the 2017 American Heart Association scientific statement on KD related to diagnosis, cardiac imaging in acute KD treatment, and long-term management. Criteria defining North American patients at high risk for developing coronary artery aneurysms who may benefit from more intensive initial treatment have been published. Advances in cardiovascular imaging have improved the ability to identify coronary artery stenosis in patients with KD, yet knowledge gaps remain regarding optimal frequency of serial imaging and the best imaging modality to identify those at risk for inducible myocardial ischemia. Recent data have advanced the understanding of safety and dosing for several anti-inflammatory therapies in KD. New anticoagulation medication, myocardial infarction management, transition of health care for patients with KD, and future directions in research are discussed.
川崎病(KD)是一种急性自限性发热疾病,主要影响儿童
{"title":"Update on Diagnosis and Management of Kawasaki Disease: A Scientific Statement From the American Heart Association.","authors":"Pei-Ni Jone, Adriana Tremoulet, Nadine Choueiter, Samuel R Dominguez, Ashraf S Harahsheh, Yoshihide Mitani, Meghan Zimmerman, Ming-Tai Lin, Kevin G Friedman","doi":"10.1161/CIR.0000000000001295","DOIUrl":"10.1161/CIR.0000000000001295","url":null,"abstract":"<p><p>Kawasaki disease (KD), an acute self-limited febrile illness that primarily affects children <5 years old, is the leading cause of acquired heart disease in developed countries, with the potential of leading to coronary artery dilation and coronary artery aneurysms in 25% of untreated patients. This update summarizes relevant clinical data published since the 2017 American Heart Association scientific statement on KD related to diagnosis, cardiac imaging in acute KD treatment, and long-term management. Criteria defining North American patients at high risk for developing coronary artery aneurysms who may benefit from more intensive initial treatment have been published. Advances in cardiovascular imaging have improved the ability to identify coronary artery stenosis in patients with KD, yet knowledge gaps remain regarding optimal frequency of serial imaging and the best imaging modality to identify those at risk for inducible myocardial ischemia. Recent data have advanced the understanding of safety and dosing for several anti-inflammatory therapies in KD. New anticoagulation medication, myocardial infarction management, transition of health care for patients with KD, and future directions in research are discussed.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":"e481-e500"},"PeriodicalIF":35.5,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142615958","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}
Pub Date : 2024-12-03Epub Date: 2024-09-01DOI: 10.1161/CIRCULATIONAHA.124.071176
Katrin Kemp Gudmundsdottir, Emma Svennberg, Leif Friberg, Tove Hygrell, Viveka Frykman, Faris Al-Khalili, Ziad Hijazi, Mårten Rosenqvist, Johan Engdahl
Background: Guidelines have suggested screening for atrial fibrillation to enable early treatment and avoid downstream negative clinical events. We aimed to determine whether atrial fibrillation screening potentially enhanced by NT-proBNP (N-terminal pro-B-type natriuretic peptide) would reduce stroke or systemic embolism incidence compared with a control group and to determine whether it was safe for those with low NT-proBNP concentrations to forfeit prolonged screening.
Methods: In this randomized controlled trial, all 75- and 76-year-old individuals in Stockholm Region, Sweden, were randomized 1:1 to be invited to screening or serve as a control group. NT-proBNP concentrations were measured, and a single-lead ECG was registered only once if NT-proBNP <125 ng/L, whereas if NT-proBNP ≥125 ng/L, participants underwent prolonged screening, recording single-lead ECGs 4 times daily for 2 weeks. If atrial fibrillation was detected, treatment was initiated. Baseline and outcome data were collected from Swedish National Registries.
Results: In total, 28 712 individuals were randomized. After exclusion of death and emigration, 13 905 remained in the intervention group, 13 884 in the control group. The participation rate in the intervention group was 49.2% (6843 of 13 905). Participants in the high NT-proBNP group (NT-proBNP≥125 ng/L) without previous atrial fibrillation constituted 60% of the total and underwent prolonged screening. New atrial fibrillation was detected in 2.4% (165 of 6843) in the intervention group. There was no difference in atrial fibrillation prevalence or oral anticoagulant treatment between the intervention and the control group after 5 years of follow-up. After a median of 5.1 years (interquartile range, 5.0-5.8), there was no difference in the primary outcome of stroke or systemic embolism between the intervention group and the control group (hazard ratio, 0.96 [95% CI, 0.86-1.06]). The low NT-proBNP group had significantly fewer strokes or systemic emboli than the control group (hazard ratio, 0.59 [95% CI, 0.46-0.74]; P<0.001). In the high NT-proBNP group, the risk of stroke or systemic embolism was higher compared with the low NT-proBNP group (hazard ratio, 1.57 [95% CI, 1.22-2.02]; P=0.001).
Conclusions: In this population-based screening trial for atrial fibrillation using NT-proBNP for screening enhancement, there was no difference in risk of stroke or systemic embolism for the intervention group compared with controls. Participation was moderate. The use of NT-proBNP for screening enhancement was safe in identifying low-risk participants.
{"title":"Randomized Invitation to Systematic NT-proBNP and ECG Screening in 75-Year-Olds to Detect Atrial Fibrillation: STROKESTOP II.","authors":"Katrin Kemp Gudmundsdottir, Emma Svennberg, Leif Friberg, Tove Hygrell, Viveka Frykman, Faris Al-Khalili, Ziad Hijazi, Mårten Rosenqvist, Johan Engdahl","doi":"10.1161/CIRCULATIONAHA.124.071176","DOIUrl":"10.1161/CIRCULATIONAHA.124.071176","url":null,"abstract":"<p><strong>Background: </strong>Guidelines have suggested screening for atrial fibrillation to enable early treatment and avoid downstream negative clinical events. We aimed to determine whether atrial fibrillation screening potentially enhanced by NT-proBNP (N-terminal pro-B-type natriuretic peptide) would reduce stroke or systemic embolism incidence compared with a control group and to determine whether it was safe for those with low NT-proBNP concentrations to forfeit prolonged screening.</p><p><strong>Methods: </strong>In this randomized controlled trial, all 75- and 76-year-old individuals in Stockholm Region, Sweden, were randomized 1:1 to be invited to screening or serve as a control group. NT-proBNP concentrations were measured, and a single-lead ECG was registered only once if NT-proBNP <125 ng/L, whereas if NT-proBNP ≥125 ng/L, participants underwent prolonged screening, recording single-lead ECGs 4 times daily for 2 weeks. If atrial fibrillation was detected, treatment was initiated. Baseline and outcome data were collected from Swedish National Registries.</p><p><strong>Results: </strong>In total, 28 712 individuals were randomized. After exclusion of death and emigration, 13 905 remained in the intervention group, 13 884 in the control group. The participation rate in the intervention group was 49.2% (6843 of 13 905). Participants in the high NT-proBNP group (NT-proBNP≥125 ng/L) without previous atrial fibrillation constituted 60% of the total and underwent prolonged screening. New atrial fibrillation was detected in 2.4% (165 of 6843) in the intervention group. There was no difference in atrial fibrillation prevalence or oral anticoagulant treatment between the intervention and the control group after 5 years of follow-up. After a median of 5.1 years (interquartile range, 5.0-5.8), there was no difference in the primary outcome of stroke or systemic embolism between the intervention group and the control group (hazard ratio, 0.96 [95% CI, 0.86-1.06]). The low NT-proBNP group had significantly fewer strokes or systemic emboli than the control group (hazard ratio, 0.59 [95% CI, 0.46-0.74]; <i>P</i><0.001). In the high NT-proBNP group, the risk of stroke or systemic embolism was higher compared with the low NT-proBNP group (hazard ratio, 1.57 [95% CI, 1.22-2.02]; <i>P</i>=0.001).</p><p><strong>Conclusions: </strong>In this population-based screening trial for atrial fibrillation using NT-proBNP for screening enhancement, there was no difference in risk of stroke or systemic embolism for the intervention group compared with controls. Participation was moderate. The use of NT-proBNP for screening enhancement was safe in identifying low-risk participants.</p><p><strong>Registration: </strong>URL: https://www.clinicaltrials.gov; Unique identifier: NCT02743416.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":"1837-1846"},"PeriodicalIF":35.5,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142104897","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}