Douglas E Cannie, Alexandros Protonotarios, Athanasios Bakalakos, Petros Syrris, Massimiliano Lorenzini, Bianca De Stavola, Louise Bjerregaard, Anne M Dybro, Thomas M Hey, Frederikke G Hansen, Marina Navarro Peñalver, Maria G Crespo-Leiro, Jose M Larrañaga-Moreira, Fernando de Frutos, Renee Johnson, Thomas A Slater, Lorenzo Monserrat, Anshuman Sengupta, Luisa Mestroni, Matthew R G Taylor, Gianfranco Sinagra, Zofia Bilinska, Itziar Solla-Ruiz, Xabier Arana Achaga, Roberto Barriales-Villa, Pablo Garcia-Pavia, Juan R Gimeno, Matteo Dal Ferro, Marco Merlo, Karim Wahbi, Diane Fatkin, Jens Mogensen, Torsten B Rasmussen, Perry M Elliott
{"title":"RBM20变体携带者发生室性心律失常和心力衰竭的风险。","authors":"Douglas E Cannie, Alexandros Protonotarios, Athanasios Bakalakos, Petros Syrris, Massimiliano Lorenzini, Bianca De Stavola, Louise Bjerregaard, Anne M Dybro, Thomas M Hey, Frederikke G Hansen, Marina Navarro Peñalver, Maria G Crespo-Leiro, Jose M Larrañaga-Moreira, Fernando de Frutos, Renee Johnson, Thomas A Slater, Lorenzo Monserrat, Anshuman Sengupta, Luisa Mestroni, Matthew R G Taylor, Gianfranco Sinagra, Zofia Bilinska, Itziar Solla-Ruiz, Xabier Arana Achaga, Roberto Barriales-Villa, Pablo Garcia-Pavia, Juan R Gimeno, Matteo Dal Ferro, Marco Merlo, Karim Wahbi, Diane Fatkin, Jens Mogensen, Torsten B Rasmussen, Perry M Elliott","doi":"10.1161/CIRCGEN.123.004059","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Variants in <i>RBM20</i> are reported in 2% to 6% of familial cases of dilated cardiomyopathy and may be associated with fatal ventricular arrhythmia and rapid heart failure progression. We sought to determine the risk of adverse events in <i>RBM20</i> variant carriers and the impact of sex on outcomes.</p><p><strong>Methods: </strong>Consecutive probands and relatives carrying <i>RBM20</i> variants were retrospectively recruited from 12 cardiomyopathy units. The primary end point was a composite of malignant ventricular arrhythmia (MVA) and end-stage heart failure (ESHF). MVA and ESHF end points were also analyzed separately and men and women compared. Left ventricular ejection fraction (LVEF) contemporary to MVA was examined. <i>RBM20</i> variant carriers with left ventricular systolic dysfunction (<i>RBM20</i><sub>LVSD</sub>) were compared with variant-elusive patients with idiopathic left ventricular systolic dysfunction.</p><p><strong>Results: </strong>Longitudinal follow-up data were available for 143 <i>RBM20</i> variant carriers (71 men; median age, 35.5 years); 7 of 143 had an MVA event at baseline. Thirty of 136 without baseline MVA (22.0%) reached the primary end point, and 16 of 136 (11.8%) had new MVA with no significant difference between men and women (log-rank <i>P</i>=0.07 and <i>P</i>=0.98, respectively). Twenty of 143 (14.0%) developed ESHF (17 men and 3 women; log-rank <i>P</i><0.001). Four of 10 variant carriers with available LVEF contemporary to MVA had an LVEF >35%. At 5 years, 15 of 67 (22.4%) <i>RBM20</i><sub>LVSD</sub> versus 7 of 197 (3.6%) patients with idiopathic left ventricular systolic dysfunction had reached the primary end point (log-rank <i>P</i><0.001). <i>RBM20</i> variant carriage conferred a 6.0-fold increase in risk of the primary end point.</p><p><strong>Conclusions: </strong><i>RBM20</i> variants are associated with a high risk of MVA and ESHF compared with idiopathic left ventricular systolic dysfunction. The risk of MVA in male and female <i>RBM20</i> variant carriers is similar, but male sex is strongly associated with ESHF.</p>","PeriodicalId":10326,"journal":{"name":"Circulation: Genomic and Precision Medicine","volume":" ","pages":"434-441"},"PeriodicalIF":6.0000,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10581410/pdf/","citationCount":"0","resultStr":"{\"title\":\"Risks of Ventricular Arrhythmia and Heart Failure in Carriers of <i>RBM20</i> Variants.\",\"authors\":\"Douglas E Cannie, Alexandros Protonotarios, Athanasios Bakalakos, Petros Syrris, Massimiliano Lorenzini, Bianca De Stavola, Louise Bjerregaard, Anne M Dybro, Thomas M Hey, Frederikke G Hansen, Marina Navarro Peñalver, Maria G Crespo-Leiro, Jose M Larrañaga-Moreira, Fernando de Frutos, Renee Johnson, Thomas A Slater, Lorenzo Monserrat, Anshuman Sengupta, Luisa Mestroni, Matthew R G Taylor, Gianfranco Sinagra, Zofia Bilinska, Itziar Solla-Ruiz, Xabier Arana Achaga, Roberto Barriales-Villa, Pablo Garcia-Pavia, Juan R Gimeno, Matteo Dal Ferro, Marco Merlo, Karim Wahbi, Diane Fatkin, Jens Mogensen, Torsten B Rasmussen, Perry M Elliott\",\"doi\":\"10.1161/CIRCGEN.123.004059\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Variants in <i>RBM20</i> are reported in 2% to 6% of familial cases of dilated cardiomyopathy and may be associated with fatal ventricular arrhythmia and rapid heart failure progression. We sought to determine the risk of adverse events in <i>RBM20</i> variant carriers and the impact of sex on outcomes.</p><p><strong>Methods: </strong>Consecutive probands and relatives carrying <i>RBM20</i> variants were retrospectively recruited from 12 cardiomyopathy units. The primary end point was a composite of malignant ventricular arrhythmia (MVA) and end-stage heart failure (ESHF). MVA and ESHF end points were also analyzed separately and men and women compared. Left ventricular ejection fraction (LVEF) contemporary to MVA was examined. <i>RBM20</i> variant carriers with left ventricular systolic dysfunction (<i>RBM20</i><sub>LVSD</sub>) were compared with variant-elusive patients with idiopathic left ventricular systolic dysfunction.</p><p><strong>Results: </strong>Longitudinal follow-up data were available for 143 <i>RBM20</i> variant carriers (71 men; median age, 35.5 years); 7 of 143 had an MVA event at baseline. Thirty of 136 without baseline MVA (22.0%) reached the primary end point, and 16 of 136 (11.8%) had new MVA with no significant difference between men and women (log-rank <i>P</i>=0.07 and <i>P</i>=0.98, respectively). Twenty of 143 (14.0%) developed ESHF (17 men and 3 women; log-rank <i>P</i><0.001). Four of 10 variant carriers with available LVEF contemporary to MVA had an LVEF >35%. At 5 years, 15 of 67 (22.4%) <i>RBM20</i><sub>LVSD</sub> versus 7 of 197 (3.6%) patients with idiopathic left ventricular systolic dysfunction had reached the primary end point (log-rank <i>P</i><0.001). <i>RBM20</i> variant carriage conferred a 6.0-fold increase in risk of the primary end point.</p><p><strong>Conclusions: </strong><i>RBM20</i> variants are associated with a high risk of MVA and ESHF compared with idiopathic left ventricular systolic dysfunction. The risk of MVA in male and female <i>RBM20</i> variant carriers is similar, but male sex is strongly associated with ESHF.</p>\",\"PeriodicalId\":10326,\"journal\":{\"name\":\"Circulation: Genomic and Precision Medicine\",\"volume\":\" \",\"pages\":\"434-441\"},\"PeriodicalIF\":6.0000,\"publicationDate\":\"2023-10-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10581410/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Circulation: Genomic and Precision Medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1161/CIRCGEN.123.004059\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2023/8/18 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"CARDIAC & CARDIOVASCULAR SYSTEMS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Circulation: Genomic and Precision Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1161/CIRCGEN.123.004059","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/8/18 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"CARDIAC & CARDIOVASCULAR SYSTEMS","Score":null,"Total":0}
Risks of Ventricular Arrhythmia and Heart Failure in Carriers of RBM20 Variants.
Background: Variants in RBM20 are reported in 2% to 6% of familial cases of dilated cardiomyopathy and may be associated with fatal ventricular arrhythmia and rapid heart failure progression. We sought to determine the risk of adverse events in RBM20 variant carriers and the impact of sex on outcomes.
Methods: Consecutive probands and relatives carrying RBM20 variants were retrospectively recruited from 12 cardiomyopathy units. The primary end point was a composite of malignant ventricular arrhythmia (MVA) and end-stage heart failure (ESHF). MVA and ESHF end points were also analyzed separately and men and women compared. Left ventricular ejection fraction (LVEF) contemporary to MVA was examined. RBM20 variant carriers with left ventricular systolic dysfunction (RBM20LVSD) were compared with variant-elusive patients with idiopathic left ventricular systolic dysfunction.
Results: Longitudinal follow-up data were available for 143 RBM20 variant carriers (71 men; median age, 35.5 years); 7 of 143 had an MVA event at baseline. Thirty of 136 without baseline MVA (22.0%) reached the primary end point, and 16 of 136 (11.8%) had new MVA with no significant difference between men and women (log-rank P=0.07 and P=0.98, respectively). Twenty of 143 (14.0%) developed ESHF (17 men and 3 women; log-rank P<0.001). Four of 10 variant carriers with available LVEF contemporary to MVA had an LVEF >35%. At 5 years, 15 of 67 (22.4%) RBM20LVSD versus 7 of 197 (3.6%) patients with idiopathic left ventricular systolic dysfunction had reached the primary end point (log-rank P<0.001). RBM20 variant carriage conferred a 6.0-fold increase in risk of the primary end point.
Conclusions: RBM20 variants are associated with a high risk of MVA and ESHF compared with idiopathic left ventricular systolic dysfunction. The risk of MVA in male and female RBM20 variant carriers is similar, but male sex is strongly associated with ESHF.
期刊介绍：
Circulation: Genomic and Precision Medicine is a distinguished journal dedicated to advancing the frontiers of cardiovascular genomics and precision medicine. It publishes a diverse array of original research articles that delve into the genetic and molecular underpinnings of cardiovascular diseases. The journal's scope is broad, encompassing studies from human subjects to laboratory models, and from in vitro experiments to computational simulations.
Circulation: Genomic and Precision Medicine is committed to publishing studies that have direct relevance to human cardiovascular biology and disease, with the ultimate goal of improving patient care and outcomes. The journal serves as a platform for researchers to share their groundbreaking work, fostering collaboration and innovation in the field of cardiovascular genomics and precision medicine.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
