Pub Date : 2024-11-17DOI: 10.1001/jamacardio.2024.4639
Ziang Yang, Xieraili Tiemuerniyazi, Fei Xu, Yang Wang, Yang Sun, Peng Yan, Liangxin Tian, Chao Han, Yan Zhang, Shiwei Pan, Zhan Hu, Xi Li, Wei Zhao, Wei Feng
Importance: Efficient approaches to prevent postoperative atrial fibrillation (POAF) after coronary artery bypass grafting (CABG) are still needed.
Objective: To investigate whether partial cardiac denervation, achieved by cutting off the ligament of Marshall (LOM) and resecting the fat pad along the Waterston groove, can reduce the risk of POAF following CABG.
Design, setting and participants: This single-center, randomized clinical trial enrolled adult patients scheduled for isolated CABG in China. Enrollment was from August 15, 2022, to December 13, 2023; follow-up visits were 30 days after discharge.
Interventions: Participants were randomized into the intervention group (CABG plus partial cardiac denervation) and the control group (CABG only) in a 1:1 pattern. All participants were continuously monitored for the incidence of POAF until day 6 after the operation.
Main outcome and measures: The primary end point was the incidence of POAF in 6 days, defined as a supraventricular arrhythmia lasting for more than 30 seconds.
Results: The trial enrolled 430 patients (79 [18.4%] female; mean [SD] age, 61.9 [7.8] years). Compared with the control group, the 6-day incidence of POAF was significantly lower in the intervention group (18.1% vs 31.6%; P = .001; risk ratio, 0.57 [95% CI, 0.41-0.81]). To further support these results, a sensitivity analysis performed with Kaplan-Meier survival curves also showed a significant reduction in the occurrence of POAF in the intervention group (hazard ratio, 0.53 [95% CI, 0.36-0.79]; P = .002). Safety assessments showed no difference between the 2 groups, while postoperative medical cost was reduced in the intervention group.
Conclusions and relevance: This randomized clinical trial found that partial cardiac denervation was an effective procedure to reduce the occurrence of POAF after isolated CABG without additional postoperative complications. These results suggest that partial cardiac denervation may be a good option for cardiac surgeons to consider for preventing POAF after CABG.
{"title":"Partial Cardiac Denervation to Prevent Postoperative Atrial Fibrillation After Coronary Artery Bypass Grafting: The pCAD-POAF Randomized Clinical Trial.","authors":"Ziang Yang, Xieraili Tiemuerniyazi, Fei Xu, Yang Wang, Yang Sun, Peng Yan, Liangxin Tian, Chao Han, Yan Zhang, Shiwei Pan, Zhan Hu, Xi Li, Wei Zhao, Wei Feng","doi":"10.1001/jamacardio.2024.4639","DOIUrl":"10.1001/jamacardio.2024.4639","url":null,"abstract":"<p><strong>Importance: </strong>Efficient approaches to prevent postoperative atrial fibrillation (POAF) after coronary artery bypass grafting (CABG) are still needed.</p><p><strong>Objective: </strong>To investigate whether partial cardiac denervation, achieved by cutting off the ligament of Marshall (LOM) and resecting the fat pad along the Waterston groove, can reduce the risk of POAF following CABG.</p><p><strong>Design, setting and participants: </strong>This single-center, randomized clinical trial enrolled adult patients scheduled for isolated CABG in China. Enrollment was from August 15, 2022, to December 13, 2023; follow-up visits were 30 days after discharge.</p><p><strong>Interventions: </strong>Participants were randomized into the intervention group (CABG plus partial cardiac denervation) and the control group (CABG only) in a 1:1 pattern. All participants were continuously monitored for the incidence of POAF until day 6 after the operation.</p><p><strong>Main outcome and measures: </strong>The primary end point was the incidence of POAF in 6 days, defined as a supraventricular arrhythmia lasting for more than 30 seconds.</p><p><strong>Results: </strong>The trial enrolled 430 patients (79 [18.4%] female; mean [SD] age, 61.9 [7.8] years). Compared with the control group, the 6-day incidence of POAF was significantly lower in the intervention group (18.1% vs 31.6%; P = .001; risk ratio, 0.57 [95% CI, 0.41-0.81]). To further support these results, a sensitivity analysis performed with Kaplan-Meier survival curves also showed a significant reduction in the occurrence of POAF in the intervention group (hazard ratio, 0.53 [95% CI, 0.36-0.79]; P = .002). Safety assessments showed no difference between the 2 groups, while postoperative medical cost was reduced in the intervention group.</p><p><strong>Conclusions and relevance: </strong>This randomized clinical trial found that partial cardiac denervation was an effective procedure to reduce the occurrence of POAF after isolated CABG without additional postoperative complications. These results suggest that partial cardiac denervation may be a good option for cardiac surgeons to consider for preventing POAF after CABG.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov Identifier: NCT05009914.</p>","PeriodicalId":14657,"journal":{"name":"JAMA cardiology","volume":" ","pages":""},"PeriodicalIF":14.8,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11571071/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142644136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-17DOI: 10.1001/jamacardio.2024.4578
Adam Ioannou, Yousuf Razvi, Aldostefano Porcari, Muhammad U. Rauf, Ana Martinez-Naharro, Lucia Venneri, Salsabeel Kazi, Ali Pasyar, Carina M. Luxhøj, Aviva Petrie, William Moody, Richard P. Steeds, Brett W. Sperry, Ronald M. Witteles, Carol Whelan, Ashutosh Wechalekar, Helen Lachmann, Philip N. Hawkins, Scott D. Solomon, Julian D. Gillmore, Marianna Fontana
ImportanceTransthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive cardiomyopathy that commonly presents with concomitant chronic kidney disease. Chronic kidney dysfunction is associated with worse outcomes, but the prognostic value of changes in kidney function over time has yet to be defined.ObjectiveTo assess the prognostic importance of a decline in estimated glomerular filtration rate (eGFR) in a large cohort of patients with ATTR-CM.Design, Setting, and ParticipantsThis retrospective, observational, single-center cohort study evaluated patients diagnosed with ATTR-CM at the National Amyloidosis Centre (NAC) in the UK who underwent an eGFR baseline assessment and a follow-up assessment at 1 year between January 2000 and April 2024. Data analysis was performed in June 2024.Main Outcomes and MeasuresThe primary outcome was the risk of all-cause mortality associated with decline in kidney function (defined as a decrease in eGFR &gt;20%).ResultsAmong 2001 patients, mean (SD) age was 75.5 (8.4) years, and 263 patients (13.1%) were female. The median (IQR) change in eGFR was −5 mlL/min/1.73 m<jats:sup>2</jats:sup> (−12 to 1), and 481 patients (24.0%) experienced decline in kidney function. Patients who experienced decline in kidney function more often had the p.(V142I) genotype than patients with stable kidney function (99 [20.6%] vs 202 [13.3%]; <jats:italic>P</jats:italic> &lt; .001) and had a more severe cardiac phenotype at baseline, as evidenced by higher median (IQR) concentrations of serum cardiac biomarkers (N-terminal pro-B-type natriuretic peptide [NT-proBNP]: 2949 pg/mL [1759-5182] vs 2309 pg/mL [1146-4290]; <jats:italic>P</jats:italic> &lt; .001; troponin T: 0.060 ng/mL [0.042-0.086] vs 0.052 ng/mL [0.033-0.074]; <jats:italic>P</jats:italic> &lt; .001), while baseline median (IQR) kidney function was similar between the 2 groups (eGFR: 63 mL/min/1.73 m<jats:sup>2</jats:sup> [51-77] vs 61 mL/min/1.73 m<jats:sup>2</jats:sup> [49-77]; <jats:italic>P</jats:italic> = .41). Decline in kidney function was associated with a 1.7-fold higher risk of mortality (hazard ratio [HR], 1.71; 95% CI, 1.43-2.04; <jats:italic>P</jats:italic> &lt; .001), with a similar risk across the 3 genotypes (wild type: HR, 1.64; 95% CI, 1.31-2.04; p.(V142I): HR, 1.70; 95% CI, 1.21-2.39; non-p.(V142I): HR, 1.51; 95% CI, 0.87-2.61) (<jats:italic>P</jats:italic> for interaction = .93) and the 3 NAC disease stages (stage 1: HR, 1.69; 95% CI, 1.22-2.32; stage 2: HR, 1.69; 95% CI, 1.30-2.18; stage 3: HR, 1.61; 95% CI, 1.11-2.35) (<jats:italic>P</jats:italic> for interaction = .97). Decline in kidney function remained independently associated with mortality after adjusting for increases in NT-proBNP and outpatient diuretic intensification (HR, 1.48; 95% CI, 1.23-2.76; <jats:italic>P</jats:italic> &lt; .001).Conclusions and RelevanceIn this retrospective cohort study, decline in kidney function was frequent in patients w
{"title":"Kidney Outcomes in Transthyretin Amyloid Cardiomyopathy","authors":"Adam Ioannou, Yousuf Razvi, Aldostefano Porcari, Muhammad U. Rauf, Ana Martinez-Naharro, Lucia Venneri, Salsabeel Kazi, Ali Pasyar, Carina M. Luxhøj, Aviva Petrie, William Moody, Richard P. Steeds, Brett W. Sperry, Ronald M. Witteles, Carol Whelan, Ashutosh Wechalekar, Helen Lachmann, Philip N. Hawkins, Scott D. Solomon, Julian D. Gillmore, Marianna Fontana","doi":"10.1001/jamacardio.2024.4578","DOIUrl":"https://doi.org/10.1001/jamacardio.2024.4578","url":null,"abstract":"ImportanceTransthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive cardiomyopathy that commonly presents with concomitant chronic kidney disease. Chronic kidney dysfunction is associated with worse outcomes, but the prognostic value of changes in kidney function over time has yet to be defined.ObjectiveTo assess the prognostic importance of a decline in estimated glomerular filtration rate (eGFR) in a large cohort of patients with ATTR-CM.Design, Setting, and ParticipantsThis retrospective, observational, single-center cohort study evaluated patients diagnosed with ATTR-CM at the National Amyloidosis Centre (NAC) in the UK who underwent an eGFR baseline assessment and a follow-up assessment at 1 year between January 2000 and April 2024. Data analysis was performed in June 2024.Main Outcomes and MeasuresThe primary outcome was the risk of all-cause mortality associated with decline in kidney function (defined as a decrease in eGFR &amp;gt;20%).ResultsAmong 2001 patients, mean (SD) age was 75.5 (8.4) years, and 263 patients (13.1%) were female. The median (IQR) change in eGFR was −5 mlL/min/1.73 m<jats:sup>2</jats:sup> (−12 to 1), and 481 patients (24.0%) experienced decline in kidney function. Patients who experienced decline in kidney function more often had the p.(V142I) genotype than patients with stable kidney function (99 [20.6%] vs 202 [13.3%]; <jats:italic>P</jats:italic> &amp;lt; .001) and had a more severe cardiac phenotype at baseline, as evidenced by higher median (IQR) concentrations of serum cardiac biomarkers (N-terminal pro-B-type natriuretic peptide [NT-proBNP]: 2949 pg/mL [1759-5182] vs 2309 pg/mL [1146-4290]; <jats:italic>P</jats:italic> &amp;lt; .001; troponin T: 0.060 ng/mL [0.042-0.086] vs 0.052 ng/mL [0.033-0.074]; <jats:italic>P</jats:italic> &amp;lt; .001), while baseline median (IQR) kidney function was similar between the 2 groups (eGFR: 63 mL/min/1.73 m<jats:sup>2</jats:sup> [51-77] vs 61 mL/min/1.73 m<jats:sup>2</jats:sup> [49-77]; <jats:italic>P</jats:italic> = .41). Decline in kidney function was associated with a 1.7-fold higher risk of mortality (hazard ratio [HR], 1.71; 95% CI, 1.43-2.04; <jats:italic>P</jats:italic> &amp;lt; .001), with a similar risk across the 3 genotypes (wild type: HR, 1.64; 95% CI, 1.31-2.04; p.(V142I): HR, 1.70; 95% CI, 1.21-2.39; non-p.(V142I): HR, 1.51; 95% CI, 0.87-2.61) (<jats:italic>P</jats:italic> for interaction = .93) and the 3 NAC disease stages (stage 1: HR, 1.69; 95% CI, 1.22-2.32; stage 2: HR, 1.69; 95% CI, 1.30-2.18; stage 3: HR, 1.61; 95% CI, 1.11-2.35) (<jats:italic>P</jats:italic> for interaction = .97). Decline in kidney function remained independently associated with mortality after adjusting for increases in NT-proBNP and outpatient diuretic intensification (HR, 1.48; 95% CI, 1.23-2.76; <jats:italic>P</jats:italic> &amp;lt; .001).Conclusions and RelevanceIn this retrospective cohort study, decline in kidney function was frequent in patients w","PeriodicalId":14657,"journal":{"name":"JAMA cardiology","volume":"76 1","pages":""},"PeriodicalIF":24.0,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142645837","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 : 2024-11-17DOI: 10.1001/jamacardio.2024.4550
Gregg C Fonarow, Eric D Peterson, Adrian F Hernandez
{"title":"The Fine Art and Science of Translating Trials Results Into Clinical Practice.","authors":"Gregg C Fonarow, Eric D Peterson, Adrian F Hernandez","doi":"10.1001/jamacardio.2024.4550","DOIUrl":"https://doi.org/10.1001/jamacardio.2024.4550","url":null,"abstract":"","PeriodicalId":14657,"journal":{"name":"JAMA cardiology","volume":" ","pages":""},"PeriodicalIF":14.8,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142644144","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 : 2024-11-16DOI: 10.1001/jamacardio.2024.4596
James P MacNamara, Christopher M Hearon, Giorgio Manferdelli, Aman M Shah, Kevin G Tayon, Ambarish Pandey, Satyam Sarma, Benjamin D Levine
{"title":"Heart Failure in Zero Gravity-External Constraint and Cardiac Hemodynamics.","authors":"James P MacNamara, Christopher M Hearon, Giorgio Manferdelli, Aman M Shah, Kevin G Tayon, Ambarish Pandey, Satyam Sarma, Benjamin D Levine","doi":"10.1001/jamacardio.2024.4596","DOIUrl":"10.1001/jamacardio.2024.4596","url":null,"abstract":"","PeriodicalId":14657,"journal":{"name":"JAMA cardiology","volume":" ","pages":""},"PeriodicalIF":14.8,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11569412/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142644132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-15DOI: 10.1001/jamacardio.2024.4470
Mohammad Abdel Jawad, Philip G. Jones, Suzanne V. Arnold, David J. Cohen, Charles F. Sherrod, Mirza S. Khan, Nobuhiro Ikemura, Paul S. Chan, John A. Spertus
ImportanceThe Kansas City Cardiomyopathy Questionnaire (KCCQ) is a commonly used outcome in heart failure trials. While comparing means between treatment groups improves statistical power, mean treatment effects do not necessarily reflect the clinical benefit experienced by individual patients.ObjectiveTo evaluate the association between mean KCCQ treatment effects and the proportions of patients experiencing clinically important improvements across a range of clinical trials and heart failure etiologies.Design, Setting, and ParticipantsA patient-level analysis of 11 randomized clinical trials, including 9977 patients, was performed to examine the association between mean treatment effects and the KCCQ Overall Summary Score (OSS) and the absolute differences in the proportions of patients experiencing clinically important (≥5 points) and moderate to large (≥10 points) improvements. There was no target date range, and included studies were those for which patient-level data were available. Validation was performed in 7 additional trials. The data were analyzed between July 1 and September 15, 2023.Main Outcomes and MeasuresProportion of patients experiencing an improvement of 5 or more and 10 or more points in their KCCQ score (with each domain transformed to a range of 0 to 100 points, where higher scores represent better health status).ResultsGroup mean KCCQ-OSS differences were strongly correlated with absolute differences in clinically important changes (Spearman correlations 0.76-0.92). For example, a mean KCCQ-OSS treatment effect of 2.5 points (half of a minimally important difference for an individual patient) was associated with an absolute difference of 6.0% (95% prediction interval [PI], 4.0%-8.1%) in the proportion of patients improving 5 or more points and 5.0% (95% PI, 3.1%-7.0%) in the proportion improving 10 or more points, corresponding to a number needed to treat of 17 (95% PI, 12-25) and 20 (95% PI, 14-33), respectively.Conclusions and RelevanceInferences about clinical impacts based on population-level mean treatment effects may be misleading, since even small between-group differences may reflect clinically important treatment benefits for individual patients. Results of this study suggest that clinical trials should explicitly describe the distributions of KCCQ change at the patient level within treatment groups to support the clinical interpretation of their results.
{"title":"Interpreting Population Mean Treatment Effects in the Kansas City Cardiomyopathy Questionnaire","authors":"Mohammad Abdel Jawad, Philip G. Jones, Suzanne V. Arnold, David J. Cohen, Charles F. Sherrod, Mirza S. Khan, Nobuhiro Ikemura, Paul S. Chan, John A. Spertus","doi":"10.1001/jamacardio.2024.4470","DOIUrl":"https://doi.org/10.1001/jamacardio.2024.4470","url":null,"abstract":"ImportanceThe Kansas City Cardiomyopathy Questionnaire (KCCQ) is a commonly used outcome in heart failure trials. While comparing means between treatment groups improves statistical power, mean treatment effects do not necessarily reflect the clinical benefit experienced by individual patients.ObjectiveTo evaluate the association between mean KCCQ treatment effects and the proportions of patients experiencing clinically important improvements across a range of clinical trials and heart failure etiologies.Design, Setting, and ParticipantsA patient-level analysis of 11 randomized clinical trials, including 9977 patients, was performed to examine the association between mean treatment effects and the KCCQ Overall Summary Score (OSS) and the absolute differences in the proportions of patients experiencing clinically important (≥5 points) and moderate to large (≥10 points) improvements. There was no target date range, and included studies were those for which patient-level data were available. Validation was performed in 7 additional trials. The data were analyzed between July 1 and September 15, 2023.Main Outcomes and MeasuresProportion of patients experiencing an improvement of 5 or more and 10 or more points in their KCCQ score (with each domain transformed to a range of 0 to 100 points, where higher scores represent better health status).ResultsGroup mean KCCQ-OSS differences were strongly correlated with absolute differences in clinically important changes (Spearman correlations 0.76-0.92). For example, a mean KCCQ-OSS treatment effect of 2.5 points (half of a minimally important difference for an individual patient) was associated with an absolute difference of 6.0% (95% prediction interval [PI], 4.0%-8.1%) in the proportion of patients improving 5 or more points and 5.0% (95% PI, 3.1%-7.0%) in the proportion improving 10 or more points, corresponding to a number needed to treat of 17 (95% PI, 12-25) and 20 (95% PI, 14-33), respectively.Conclusions and RelevanceInferences about clinical impacts based on population-level mean treatment effects may be misleading, since even small between-group differences may reflect clinically important treatment benefits for individual patients. Results of this study suggest that clinical trials should explicitly describe the distributions of KCCQ change at the patient level within treatment groups to support the clinical interpretation of their results.","PeriodicalId":14657,"journal":{"name":"JAMA cardiology","volume":"46 1","pages":""},"PeriodicalIF":24.0,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142637181","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 : 2024-11-15DOI: 10.1001/jamacardio.2024.4610
James E Udelson, Clyde W Yancy, Gregg C Fonarow
{"title":"Interpreting Health Status Measures in Patients With Heart Failure-What Counts.","authors":"James E Udelson, Clyde W Yancy, Gregg C Fonarow","doi":"10.1001/jamacardio.2024.4610","DOIUrl":"https://doi.org/10.1001/jamacardio.2024.4610","url":null,"abstract":"","PeriodicalId":14657,"journal":{"name":"JAMA cardiology","volume":" ","pages":""},"PeriodicalIF":14.8,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638972","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 : 2024-11-13DOI: 10.1001/jamacardio.2024.3957
Henry E Wang
{"title":"Emergency Medical Service Agency Cardiac Arrest Practices.","authors":"Henry E Wang","doi":"10.1001/jamacardio.2024.3957","DOIUrl":"https://doi.org/10.1001/jamacardio.2024.3957","url":null,"abstract":"","PeriodicalId":14657,"journal":{"name":"JAMA cardiology","volume":" ","pages":""},"PeriodicalIF":14.8,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142620491","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 : 2024-11-13DOI: 10.1001/jamacardio.2024.3547
Joseph Park, Michael G. Levin, David Zhang, Nosheen Reza, Jonathan O. Mead, Eric D. Carruth, Melissa A. Kelly, Alex Winters, Colleen M. Kripke, Renae L. Judy, Scott M. Damrauer, Anjali T. Owens, Lisa Bastarache, Anurag Verma, Daniel D. Kinnamon, Ray E. Hershberger, Marylyn D. Ritchie, Daniel J. Rader
ImportanceThe genetic factors that modulate the reduced penetrance and variable expressivity of heritable dilated cardiomyopathy (DCM) are largely unknown. BAG3 genetic variants have been implicated in both DCM and hypertrophic cardiomyopathy (HCM), nominating BAG3 as a gene that harbors potential modifier variants in DCM.ObjectiveTo interrogate the clinical traits and diseases associated with BAG3 coding variation.Design, Setting, and ParticipantsThis was a cross-sectional study in the Penn Medicine BioBank (PMBB) enrolling patients of the University of Pennsylvania Health System’s clinical practice sites from 2014 to 2023. Whole-exome sequencing (WES) was linked to electronic health record (EHR) data to associate BAG3 coding variants with EHR phenotypes. This was a health care population-based study including individuals of European and African genetic ancestry in the PMBB with WES linked to EHR phenotypes, with replication studies in BioVU, UK Biobank, MyCode, and DCM Precision Medicine Study.ExposuresCarrier status for BAG3 coding variants.Main Outcomes and MeasuresAssociation of BAG3 coding variation with clinical diagnoses, echocardiographic traits, and longitudinal outcomes.ResultsIn PMBB (n = 43 731; median [IQR] age, 65 [50-76] years; 21 907 female [50.1%]), among 30 324 European and 11 198 African individuals, the common C151R variant was associated with decreased risk for DCM (odds ratio [OR], 0.85; 95% CI, 0.78-0.92) and simultaneous increased risk for HCM (OR, 1.59; 95% CI, 1.25-2.02), which was confirmed in the replication cohorts. C151R carriers exhibited improved longitudinal outcomes compared with noncarriers as assessed by age at death (hazard ratio [HR], 0.85; 95% CI, 0.74-0.96; median [IQR] age, 71.8 [63.1-80.7] in carriers and 70.3 [61.6-79.2] in noncarriers) and heart transplant (HR, 0.81; 95% CI, 0.66-0.99; median [IQR] age, 56.7 [46.1-63.1] in carriers and 55.6 [45.2-62.9] in noncarriers). C151R was associated with reduced risk of DCM (OR, 0.42; 95% CI, 0.24-0.74) and heart failure (OR, 0.27; 95% CI, 0.14-0.50) among individuals harboring truncating TTN variants in exons with high cardiac expression (n = 358).Conclusions and RelevanceBAG3 C151R was identified as a bidirectional modulator of risk along the DCM-HCM spectrum, as well as an important genetic modifier variant in TTN-mediated DCM. This work expands on the understanding of the etiology and penetrance of DCM, suggesting that BAG3 C151R is an important genetic modifier variant contributing to the variable expressivity of DCM, warranting further exploration of its mechanisms and of genetic modifiers in DCM more broadly.
{"title":"Bidirectional Risk Modulator and Modifier Variant of Dilated and Hypertrophic Cardiomyopathy in BAG3","authors":"Joseph Park, Michael G. Levin, David Zhang, Nosheen Reza, Jonathan O. Mead, Eric D. Carruth, Melissa A. Kelly, Alex Winters, Colleen M. Kripke, Renae L. Judy, Scott M. Damrauer, Anjali T. Owens, Lisa Bastarache, Anurag Verma, Daniel D. Kinnamon, Ray E. Hershberger, Marylyn D. Ritchie, Daniel J. Rader","doi":"10.1001/jamacardio.2024.3547","DOIUrl":"https://doi.org/10.1001/jamacardio.2024.3547","url":null,"abstract":"ImportanceThe genetic factors that modulate the reduced penetrance and variable expressivity of heritable dilated cardiomyopathy (DCM) are largely unknown. <jats:italic>BAG3</jats:italic> genetic variants have been implicated in both DCM and hypertrophic cardiomyopathy (HCM), nominating <jats:italic>BAG3</jats:italic> as a gene that harbors potential modifier variants in DCM.ObjectiveTo interrogate the clinical traits and diseases associated with <jats:italic>BAG3</jats:italic> coding variation.Design, Setting, and ParticipantsThis was a cross-sectional study in the Penn Medicine BioBank (PMBB) enrolling patients of the University of Pennsylvania Health System’s clinical practice sites from 2014 to 2023. Whole-exome sequencing (WES) was linked to electronic health record (EHR) data to associate <jats:italic>BAG3</jats:italic> coding variants with EHR phenotypes. This was a health care population-based study including individuals of European and African genetic ancestry in the PMBB with WES linked to EHR phenotypes, with replication studies in BioVU, UK Biobank, MyCode, and DCM Precision Medicine Study.ExposuresCarrier status for <jats:italic>BAG3</jats:italic> coding variants.Main Outcomes and MeasuresAssociation of <jats:italic>BAG3</jats:italic> coding variation with clinical diagnoses, echocardiographic traits, and longitudinal outcomes.ResultsIn PMBB (n = 43 731; median [IQR] age, 65 [50-76] years; 21 907 female [50.1%]), among 30 324 European and 11 198 African individuals, the common C151R variant was associated with decreased risk for DCM (odds ratio [OR], 0.85; 95% CI, 0.78-0.92) and simultaneous increased risk for HCM (OR, 1.59; 95% CI, 1.25-2.02), which was confirmed in the replication cohorts. C151R carriers exhibited improved longitudinal outcomes compared with noncarriers as assessed by age at death (hazard ratio [HR], 0.85; 95% CI, 0.74-0.96; median [IQR] age, 71.8 [63.1-80.7] in carriers and 70.3 [61.6-79.2] in noncarriers) and heart transplant (HR, 0.81; 95% CI, 0.66-0.99; median [IQR] age, 56.7 [46.1-63.1] in carriers and 55.6 [45.2-62.9] in noncarriers). C151R was associated with reduced risk of DCM (OR, 0.42; 95% CI, 0.24-0.74) and heart failure (OR, 0.27; 95% CI, 0.14-0.50) among individuals harboring truncating <jats:italic>TTN</jats:italic> variants in exons with high cardiac expression (n = 358).Conclusions and Relevance<jats:italic>BAG3</jats:italic> C151R was identified as a bidirectional modulator of risk along the DCM-HCM spectrum, as well as an important genetic modifier variant in <jats:italic>TTN</jats:italic>-mediated DCM. This work expands on the understanding of the etiology and penetrance of DCM, suggesting that <jats:italic>BAG3</jats:italic> C151R is an important genetic modifier variant contributing to the variable expressivity of DCM, warranting further exploration of its mechanisms and of genetic modifiers in DCM more broadly.","PeriodicalId":14657,"journal":{"name":"JAMA cardiology","volume":"46 1","pages":""},"PeriodicalIF":24.0,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142610300","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 : 2024-11-13DOI: 10.1001/jamacardio.2024.3954
Saket Girotra, Paul S Chan
{"title":"Emergency Medical Service Agency Cardiac Arrest Practices-Reply.","authors":"Saket Girotra, Paul S Chan","doi":"10.1001/jamacardio.2024.3954","DOIUrl":"https://doi.org/10.1001/jamacardio.2024.3954","url":null,"abstract":"","PeriodicalId":14657,"journal":{"name":"JAMA cardiology","volume":" ","pages":""},"PeriodicalIF":14.8,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142620559","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}
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