Pub Date : 2024-10-01DOI: 10.1016/j.jacep.2024.05.008
Juan Pablo Ochoa MD, PhD , Maria Ángeles Espinosa MD, PhD , Jara Gayan-Ordas MD , Andrea Fernández-Valledor MD , María Gallego-Delgado MD, PhD , Coloma Tirón MD , Adrián Lozano-Ibañez MD , José Manuel García-Pinilla MD, PhD , José F. Rodríguez-Palomares MD, PhD , José María Larrañaga-Moreira MD , Helena Llamas-Gómez MD , Tomas Ripoll-Vera MD, PhD , Aitana Braza-Boïls PhD , Silvia Vilches MD , Irene Méndez MD , Ramón Bascompte-Claret MD , Ana García-Álvarez MD, PhD , Eduardo Villacorta MD, PhD , Ignacio Fernandez-Lozano MD, PhD , Enrique Lara-Pezzi PhD , Pablo Garcia-Pavia MD, PhD
Background
Genetic disease has recently emerged as a cause of cardiac conduction disorders (CCDs), but the diagnostic yield of genetic testing and the contribution of the different genes to CCD is still unsettled.
Objectives
This study sought to determine the diagnostic yield of genetic testing in young adults with CCD of unknown etiology requiring pacemaker implantation. We also studied the prevalence of rare protein-altering variants across individual genes and functional gene groups.
Methods
We performed whole exome sequencing in 150 patients with CCD of unknown etiology who had permanent pacemaker implanted at age ≤60 years at 14 Spanish hospitals. Prevalence of rare protein-altering variants in patients with CCD was compared with a reference population of 115,522 individuals from gnomAD database (control subjects).
Results
Among 39 prioritized genes, patients with CCD had more rare protein-altering variants than control subjects (OR: 2.39; 95% CI: 1.75-3.33). Significant enrichment of rare variants in patients with CCD was observed in all functional gene groups except in the desmosomal genes group. Rare variants in the nuclear envelope genes group exhibited the strongest association with CCD (OR: 6.77; 95% CI: 3.71-13.87). Of note, rare variants in sarcomeric genes were also enriched (OR: 1.73; 95% CI: 1.05-3.10). An actionable genetic variant was detected in 21 patients (14%), with LMNA being the most frequently involved gene (4.6%).
Conclusions
Unrecognized rare genetic variants increase the risk of CCD in young adults with CCD of unknown etiology. Genetic testing should be performed in patients age ≤60 years with CCD of unknown etiology. The role of genetic variants in sarcomeric genes as a cause of CCD should be further investigated.
{"title":"Rare Genetic Variants in Young Adults Requiring Pacemaker Implantation","authors":"Juan Pablo Ochoa MD, PhD , Maria Ángeles Espinosa MD, PhD , Jara Gayan-Ordas MD , Andrea Fernández-Valledor MD , María Gallego-Delgado MD, PhD , Coloma Tirón MD , Adrián Lozano-Ibañez MD , José Manuel García-Pinilla MD, PhD , José F. Rodríguez-Palomares MD, PhD , José María Larrañaga-Moreira MD , Helena Llamas-Gómez MD , Tomas Ripoll-Vera MD, PhD , Aitana Braza-Boïls PhD , Silvia Vilches MD , Irene Méndez MD , Ramón Bascompte-Claret MD , Ana García-Álvarez MD, PhD , Eduardo Villacorta MD, PhD , Ignacio Fernandez-Lozano MD, PhD , Enrique Lara-Pezzi PhD , Pablo Garcia-Pavia MD, PhD","doi":"10.1016/j.jacep.2024.05.008","DOIUrl":"10.1016/j.jacep.2024.05.008","url":null,"abstract":"<div><h3>Background</h3><div>Genetic disease has recently emerged as a cause of cardiac conduction disorders (CCDs), but the diagnostic yield of genetic testing and the contribution of the different genes to CCD is still unsettled.</div></div><div><h3>Objectives</h3><div>This study sought to determine the diagnostic yield of genetic testing in young adults with CCD of unknown etiology requiring pacemaker implantation. We also studied the prevalence of rare protein-altering variants across individual genes and functional gene groups.</div></div><div><h3>Methods</h3><div>We performed whole exome sequencing in 150 patients with CCD of unknown etiology who had permanent pacemaker implanted at age ≤60 years at 14 Spanish hospitals. Prevalence of rare protein-altering variants in patients with CCD was compared with a reference population of 115,522 individuals from gnomAD database (control subjects).</div></div><div><h3>Results</h3><div>Among 39 prioritized genes, patients with CCD had more rare protein-altering variants than control subjects (OR: 2.39; 95% CI: 1.75-3.33). Significant enrichment of rare variants in patients with CCD was observed in all functional gene groups except in the desmosomal genes group. Rare variants in the nuclear envelope genes group exhibited the strongest association with CCD (OR: 6.77; 95% CI: 3.71-13.87). Of note, rare variants in sarcomeric genes were also enriched (OR: 1.73; 95% CI: 1.05-3.10). An actionable genetic variant was detected in 21 patients (14%), with <em>LMNA</em> being the most frequently involved gene (4.6%).</div></div><div><h3>Conclusions</h3><div>Unrecognized rare genetic variants increase the risk of CCD in young adults with CCD of unknown etiology. Genetic testing should be performed in patients age ≤60 years with CCD of unknown etiology. The role of genetic variants in sarcomeric genes as a cause of CCD should be further investigated.</div></div>","PeriodicalId":14573,"journal":{"name":"JACC. Clinical electrophysiology","volume":"10 10","pages":"Pages 2250-2260"},"PeriodicalIF":8.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141603650","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 : 2024-10-01DOI: 10.1016/j.jacep.2024.06.024
Daniel J. Friedman MD , Mihail G. Chelu MD, PhD
{"title":"Left Bundle Branch Area Pacing for LBBB","authors":"Daniel J. Friedman MD , Mihail G. Chelu MD, PhD","doi":"10.1016/j.jacep.2024.06.024","DOIUrl":"10.1016/j.jacep.2024.06.024","url":null,"abstract":"","PeriodicalId":14573,"journal":{"name":"JACC. Clinical electrophysiology","volume":"10 10","pages":"Pages 2247-2249"},"PeriodicalIF":8.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142035801","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 : 2024-09-30DOI: 10.1016/j.jacep.2024.09.011
Gaurav A Upadhyay
{"title":"Predicting Clinical Success After Cardioneural Ablation for Syncope: Time to Get Into the Weeds.","authors":"Gaurav A Upadhyay","doi":"10.1016/j.jacep.2024.09.011","DOIUrl":"https://doi.org/10.1016/j.jacep.2024.09.011","url":null,"abstract":"","PeriodicalId":14573,"journal":{"name":"JACC. Clinical electrophysiology","volume":" ","pages":""},"PeriodicalIF":8.0,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142620682","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 : 2024-09-30DOI: 10.1016/j.jacep.2024.09.013
John M Miller, Tanyanan Tanawuttiwat, Nektarios Vasilottos
{"title":"Tachycardia Termination Without Global Propagation: A Stimulating Experience.","authors":"John M Miller, Tanyanan Tanawuttiwat, Nektarios Vasilottos","doi":"10.1016/j.jacep.2024.09.013","DOIUrl":"https://doi.org/10.1016/j.jacep.2024.09.013","url":null,"abstract":"","PeriodicalId":14573,"journal":{"name":"JACC. Clinical electrophysiology","volume":" ","pages":""},"PeriodicalIF":8.0,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142620706","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 : 2024-09-29DOI: 10.1016/j.jacep.2024.09.017
Jonathan P Ariyaratnam, Melissa E Middeldorp, Anthony G Brooks, Gijo Thomas, Kadhim Kadhim, Rajiv Mahajan, Rajeev K Pathak, Glenn D Young, Jonathan M Kalman, Prashanthan Sanders
Background: The coronary sinus is an arrhythmogenic structure that can initiate and maintain atrial fibrillation (AF). Coronary sinus ablation has been shown to be effective in prolonging the AF cycle length and terminating AF in patients with both paroxysmal and persistent AF who have persistent AF after pulmonary vein isolation (PVI).
Objectives: The objective of this study was to undertake a randomized controlled trial to investigate the efficacy of coronary sinus isolation (CSI) as an adjunctive ablation strategy for the treatment of high-burden AF.
Methods: Consecutive patients presenting with symptomatic long episodes of paroxysmal AF (≥48 h but ≤7 days) or persistent AF (>7 days and ≤12 months) referred for first-time ablation were enrolled. Participants were randomized to either PVI, roofline ablation, and CSI (CSI group) or PVI and roofline ablation only (non-CSI group). Participants were assessed postprocedurally via clinical follow-up and 7-day Holter monitoring at regular intervals. The primary outcome was single-procedure drug-free atrial arrhythmia-free survival at 2 years.
Results: One hundred participants were recruited to the study; 48 were randomized to the CSI group and 52 to the non-CSI group. Acutely successful CSI was achieved in 45 of the 48 patients in the CSI group. At 2 years follow up, 30 of 48 patients (62.5%) in the CSI group and 33 of 52 (63.4%) in the non-CSI group were free from arrhythmia recurrence. Single-procedure drug-free survival at 2 years was no different between groups (P = 0.91). Similarly, multiple procedure drug assisted survival at 5 years was not different between groups (P = 0.80). Complication rates were not significantly different between groups (P = 0.19).
Conclusions: Adjunctive CSI as part of a de novo ablation strategy does not confer any additional benefit greater than PVI and roofline for the treatment of high-burden AF.
{"title":"Coronary Sinus Isolation for High-Burden Atrial Fibrillation: A Randomized Clinical Trial.","authors":"Jonathan P Ariyaratnam, Melissa E Middeldorp, Anthony G Brooks, Gijo Thomas, Kadhim Kadhim, Rajiv Mahajan, Rajeev K Pathak, Glenn D Young, Jonathan M Kalman, Prashanthan Sanders","doi":"10.1016/j.jacep.2024.09.017","DOIUrl":"10.1016/j.jacep.2024.09.017","url":null,"abstract":"<p><strong>Background: </strong>The coronary sinus is an arrhythmogenic structure that can initiate and maintain atrial fibrillation (AF). Coronary sinus ablation has been shown to be effective in prolonging the AF cycle length and terminating AF in patients with both paroxysmal and persistent AF who have persistent AF after pulmonary vein isolation (PVI).</p><p><strong>Objectives: </strong>The objective of this study was to undertake a randomized controlled trial to investigate the efficacy of coronary sinus isolation (CSI) as an adjunctive ablation strategy for the treatment of high-burden AF.</p><p><strong>Methods: </strong>Consecutive patients presenting with symptomatic long episodes of paroxysmal AF (≥48 h but ≤7 days) or persistent AF (>7 days and ≤12 months) referred for first-time ablation were enrolled. Participants were randomized to either PVI, roofline ablation, and CSI (CSI group) or PVI and roofline ablation only (non-CSI group). Participants were assessed postprocedurally via clinical follow-up and 7-day Holter monitoring at regular intervals. The primary outcome was single-procedure drug-free atrial arrhythmia-free survival at 2 years.</p><p><strong>Results: </strong>One hundred participants were recruited to the study; 48 were randomized to the CSI group and 52 to the non-CSI group. Acutely successful CSI was achieved in 45 of the 48 patients in the CSI group. At 2 years follow up, 30 of 48 patients (62.5%) in the CSI group and 33 of 52 (63.4%) in the non-CSI group were free from arrhythmia recurrence. Single-procedure drug-free survival at 2 years was no different between groups (P = 0.91). Similarly, multiple procedure drug assisted survival at 5 years was not different between groups (P = 0.80). Complication rates were not significantly different between groups (P = 0.19).</p><p><strong>Conclusions: </strong>Adjunctive CSI as part of a de novo ablation strategy does not confer any additional benefit greater than PVI and roofline for the treatment of high-burden AF.</p>","PeriodicalId":14573,"journal":{"name":"JACC. Clinical electrophysiology","volume":" ","pages":""},"PeriodicalIF":8.0,"publicationDate":"2024-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142465587","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 : 2024-09-28DOI: 10.1016/j.jacep.2024.09.012
Richard J Czosek, Shankar Baskar, Chad E Connor
{"title":"Emergence of SCAI in Patients With Tetralogy of Fallot: Early Ablation Target or Moving Target.","authors":"Richard J Czosek, Shankar Baskar, Chad E Connor","doi":"10.1016/j.jacep.2024.09.012","DOIUrl":"https://doi.org/10.1016/j.jacep.2024.09.012","url":null,"abstract":"","PeriodicalId":14573,"journal":{"name":"JACC. Clinical electrophysiology","volume":" ","pages":""},"PeriodicalIF":8.0,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142620675","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 : 2024-09-27DOI: 10.1016/j.jacep.2024.09.018
Rose Crowley, David Chieng, Louise Segan, Jeremy William, Hariharan Sugumar, Sandeep Prabhu, Aleksandr Voskoboinik, Liang-Han Ling, Joseph B Morton, Geoffrey Lee, Alex J McLellan, Michael Wong, Rajeev K Pathak, Laurence Sterns, Matthew Ginks, Prashanthan Sanders, Peter M Kistler, Jonathan M Kalman
Background: Many patients with persistent atrial fibrillation (PsAF) have progressed from an initial paroxysmal phenotype; however, there are patients in whom atrial fibrillation (AF) is persistent at diagnosis. Relatively little is known about this subgroup, but prior observational studies have suggested these patients have worse outcomes with ablation.
Objectives: This study sought to: 1) assess demographic and electrophysiologic characteristics of patients with PsAF at first diagnosis compared with those with who have progressed from paroxysmal atrial fibrillation (PAF); and 2) assess the impact of pattern of AF at diagnosis on recurrence post ablation.
Methods: CAPLA (Catheter Ablation for persistent atrial fibrillation: A Multicentre randomised trial of Pulmonary vein isolation [PVI] vs PVI with posterior Left Atrial wall isolation [PWI]) was a multicenter trial that randomized patients with PsAF to PVI plus PWI or PVI alone. Follow-up was 12 months. Outcomes were assessed after a 3-month blanking period.
Results: A total of 334 patients were included (median age 65.6 years, 23.1% female), 194 (58.1%) had PsAF at first AF diagnosis and 140 (41.9%) had PAF. Patients with PsAF at diagnosis were younger (age 64.0 vs 67.7 years, P = 0.005), had higher rates of heart failure (P < 0.001), and lower left ventricular ejection fraction (54.5% IQR: 40-60 vs 60% IQR: 50-61, P = 0.007). AF recurrence occurred in 85 (43.8%) with PsAF at diagnosis and 70 (50%) with PAF at diagnosis. PsAF at diagnosis was not associated with risk of recurrence on univariable (HR: 0.802; 95% CI: 0.585-1.101; P = 0.173) or multivariable analysis (HR: 0.922; 95% CI: 0.647-1.312; P = 0.650). Median AF burden was 0% in both groups (P = 0.125). There was no difference in left atrial size (P = 0.337) or bipolar voltage (P = 0.579) between the groups.
Conclusions: In the CAPLA cohort of patients, pattern of AF at first diagnosis did not influence post-ablation rate of AF recurrence or AF burden. (Catheter Ablation for persistent atrial fibrillation: A Multicentre randomised trial of Pulmonary vein isolation [PVI] vs PVI with posterior Left Atrial wall isolation [PWI]; ACTRN12616001436460).
{"title":"Persistent Atrial Fibrillation Phenotypes and Ablation Outcomes: Persistent From Outset vs Progression From Paroxysmal AF.","authors":"Rose Crowley, David Chieng, Louise Segan, Jeremy William, Hariharan Sugumar, Sandeep Prabhu, Aleksandr Voskoboinik, Liang-Han Ling, Joseph B Morton, Geoffrey Lee, Alex J McLellan, Michael Wong, Rajeev K Pathak, Laurence Sterns, Matthew Ginks, Prashanthan Sanders, Peter M Kistler, Jonathan M Kalman","doi":"10.1016/j.jacep.2024.09.018","DOIUrl":"https://doi.org/10.1016/j.jacep.2024.09.018","url":null,"abstract":"<p><strong>Background: </strong>Many patients with persistent atrial fibrillation (PsAF) have progressed from an initial paroxysmal phenotype; however, there are patients in whom atrial fibrillation (AF) is persistent at diagnosis. Relatively little is known about this subgroup, but prior observational studies have suggested these patients have worse outcomes with ablation.</p><p><strong>Objectives: </strong>This study sought to: 1) assess demographic and electrophysiologic characteristics of patients with PsAF at first diagnosis compared with those with who have progressed from paroxysmal atrial fibrillation (PAF); and 2) assess the impact of pattern of AF at diagnosis on recurrence post ablation.</p><p><strong>Methods: </strong>CAPLA (Catheter Ablation for persistent atrial fibrillation: A Multicentre randomised trial of Pulmonary vein isolation [PVI] vs PVI with posterior Left Atrial wall isolation [PWI]) was a multicenter trial that randomized patients with PsAF to PVI plus PWI or PVI alone. Follow-up was 12 months. Outcomes were assessed after a 3-month blanking period.</p><p><strong>Results: </strong>A total of 334 patients were included (median age 65.6 years, 23.1% female), 194 (58.1%) had PsAF at first AF diagnosis and 140 (41.9%) had PAF. Patients with PsAF at diagnosis were younger (age 64.0 vs 67.7 years, P = 0.005), had higher rates of heart failure (P < 0.001), and lower left ventricular ejection fraction (54.5% IQR: 40-60 vs 60% IQR: 50-61, P = 0.007). AF recurrence occurred in 85 (43.8%) with PsAF at diagnosis and 70 (50%) with PAF at diagnosis. PsAF at diagnosis was not associated with risk of recurrence on univariable (HR: 0.802; 95% CI: 0.585-1.101; P = 0.173) or multivariable analysis (HR: 0.922; 95% CI: 0.647-1.312; P = 0.650). Median AF burden was 0% in both groups (P = 0.125). There was no difference in left atrial size (P = 0.337) or bipolar voltage (P = 0.579) between the groups.</p><p><strong>Conclusions: </strong>In the CAPLA cohort of patients, pattern of AF at first diagnosis did not influence post-ablation rate of AF recurrence or AF burden. (Catheter Ablation for persistent atrial fibrillation: A Multicentre randomised trial of Pulmonary vein isolation [PVI] vs PVI with posterior Left Atrial wall isolation [PWI]; ACTRN12616001436460).</p>","PeriodicalId":14573,"journal":{"name":"JACC. Clinical electrophysiology","volume":" ","pages":""},"PeriodicalIF":8.0,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142500588","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 : 2024-09-27DOI: 10.1016/j.jacep.2024.07.029
Zain M Virk, Majd A El-Harasis, Zachary T Yoneda, Katherine C Anderson, Lili Sun, Joseph A Quintana, Brittany S Murphy, James L Laws, Giovanni E Davogustto, Matthew J O'Neill, Bibin T Varghese, Diane M Crawford, Hollie L Williams, Mahsima Shabani, Cassady J Pelphrey, Dakota D Grauherr, Kelsey Tomasek, Yan Ru Su, Megan C Lancaster, Quinn S Wells, Jeffrey M Dendy, Pablo Saavedra, Juan C Estrada, Travis D Richardson, Sharon T Shen, Arvindh N Kanagasundram, Jay A Montgomery, Christopher R Ellis, George H Crossley, Harikrishna Tandri, Prince J Kannankeril, Steven A Lubitz, William G Stevenson, Fei Ye, Patrick T Ellinor, Lynne W Stevenson, Dan M Roden, M Benjamin Shoemaker
Background: TTN encodes a sarcomeric protein called titin. Pathogenic rare variants in TTN are the most common finding in patients with atrial fibrillation (AF) and positive genetic testing.
Objectives: This study sought to define the characteristics and outcomes in patients with AF and pathogenic TTN variants compared with genotype-negative patients with AF.
Methods: Patients who presented initially with AF were enrolled in an AF registry. Retrospectively they underwent research sequencing for cardiomyopathy and arrhythmia genes. TTN(+) AF cases were defined as participants with pathogenic or likely pathogenic (P/LP) rare variants located in exons with high cardiac expression. They were matched 1:2 with control subjects with no P/LP variants. Phenotyping used retrospective manual chart review.
Results: Among 2794 participants; 57 (2.0%) TTN(+) AF cases were identified and matched with 114 control subjects. Low QRS complex voltage was present more often in TTN(+) AF cases (18% vs 5%; P < 0.01), with no difference in PR, QRS interval, or QTc. More TTN(+) AF cases had persistent AF at enrollment (44% vs 30%; P = 0.028) and had undergone multiple cardioversions (61% vs. 37%; P < 0.01). By end of follow-up (median 8.3 years; Q1, Q3: 4.5, 13.7 years), 11% of TTN(+) AF cases developed sustained ventricular tachycardia/ventricular fibrillation, 44% left ventricular (LV) systolic dysfunction (LV ejection fraction <50%), and 47% met a combined endpoint of sustained ventricular tachycardia/ventricular fibrillation or LV systolic dysfunction.
Conclusions: TTN(+) AF patients undergo more cardioversions and have more persistent forms of AF. Approximately 50% develop LV systolic dysfunction and/or malignant ventricular arrhythmias. These results highlight the need for diagnostic evaluation and management in TTN(+) patients beyond the usual care for AF.
{"title":"Clinical Characteristics and Outcomes in Patients With Atrial Fibrillation and Pathogenic TTN Variants.","authors":"Zain M Virk, Majd A El-Harasis, Zachary T Yoneda, Katherine C Anderson, Lili Sun, Joseph A Quintana, Brittany S Murphy, James L Laws, Giovanni E Davogustto, Matthew J O'Neill, Bibin T Varghese, Diane M Crawford, Hollie L Williams, Mahsima Shabani, Cassady J Pelphrey, Dakota D Grauherr, Kelsey Tomasek, Yan Ru Su, Megan C Lancaster, Quinn S Wells, Jeffrey M Dendy, Pablo Saavedra, Juan C Estrada, Travis D Richardson, Sharon T Shen, Arvindh N Kanagasundram, Jay A Montgomery, Christopher R Ellis, George H Crossley, Harikrishna Tandri, Prince J Kannankeril, Steven A Lubitz, William G Stevenson, Fei Ye, Patrick T Ellinor, Lynne W Stevenson, Dan M Roden, M Benjamin Shoemaker","doi":"10.1016/j.jacep.2024.07.029","DOIUrl":"10.1016/j.jacep.2024.07.029","url":null,"abstract":"<p><strong>Background: </strong>TTN encodes a sarcomeric protein called titin. Pathogenic rare variants in TTN are the most common finding in patients with atrial fibrillation (AF) and positive genetic testing.</p><p><strong>Objectives: </strong>This study sought to define the characteristics and outcomes in patients with AF and pathogenic TTN variants compared with genotype-negative patients with AF.</p><p><strong>Methods: </strong>Patients who presented initially with AF were enrolled in an AF registry. Retrospectively they underwent research sequencing for cardiomyopathy and arrhythmia genes. TTN(+) AF cases were defined as participants with pathogenic or likely pathogenic (P/LP) rare variants located in exons with high cardiac expression. They were matched 1:2 with control subjects with no P/LP variants. Phenotyping used retrospective manual chart review.</p><p><strong>Results: </strong>Among 2794 participants; 57 (2.0%) TTN(+) AF cases were identified and matched with 114 control subjects. Low QRS complex voltage was present more often in TTN(+) AF cases (18% vs 5%; P < 0.01), with no difference in PR, QRS interval, or QTc. More TTN(+) AF cases had persistent AF at enrollment (44% vs 30%; P = 0.028) and had undergone multiple cardioversions (61% vs. 37%; P < 0.01). By end of follow-up (median 8.3 years; Q1, Q3: 4.5, 13.7 years), 11% of TTN(+) AF cases developed sustained ventricular tachycardia/ventricular fibrillation, 44% left ventricular (LV) systolic dysfunction (LV ejection fraction <50%), and 47% met a combined endpoint of sustained ventricular tachycardia/ventricular fibrillation or LV systolic dysfunction.</p><p><strong>Conclusions: </strong>TTN(+) AF patients undergo more cardioversions and have more persistent forms of AF. Approximately 50% develop LV systolic dysfunction and/or malignant ventricular arrhythmias. These results highlight the need for diagnostic evaluation and management in TTN(+) patients beyond the usual care for AF.</p>","PeriodicalId":14573,"journal":{"name":"JACC. Clinical electrophysiology","volume":" ","pages":""},"PeriodicalIF":8.0,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142500585","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}