Pub Date : 2024-01-01Epub Date: 2024-01-16DOI: 10.1161/HAE.0000000000000090
{"title":"Retraction of: Systematic Treatment Approach to Ventricular Tachycardia in Cardiac Sarcoidosis.","authors":"","doi":"10.1161/HAE.0000000000000090","DOIUrl":"https://doi.org/10.1161/HAE.0000000000000090","url":null,"abstract":"","PeriodicalId":10319,"journal":{"name":"Circulation. Arrhythmia and electrophysiology","volume":null,"pages":null},"PeriodicalIF":8.4,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139478134","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 : 2024-01-01Epub Date: 2023-12-28DOI: 10.1161/CIRCEP.123.012026
Hiroshi Nakagawa, Quim Castellvi, Robert Neal, Steven Girouard, Jacob Laughner, Atsushi Ikeda, Masafumi Sugawara, Yoshimori An, Ayman A Hussein, Shady Nakhla, Tyler Taigen, Jakub Srounbek, Mohamed Kanj, Pasquale Santangeli, Walid I Saliba, Antoni Ivorra, Oussama M Wazni
Background: Effects of contact force (CF) on lesion formation during pulsed field ablation (PFA) have not been well validated. The purpose of this study was to determine the relationship between average CF and lesion size during PFA using a swine-beating heart model.
Methods: A 7F catheter with a 3.5-mm ablation electrode and CF sensor (TactiCath SE, Abbott) was connected to a PFA system (CENTAURI, Galvanize Therapeutics). In 5 closed-chest swine, biphasic PFA current was delivered between the ablation electrode and a skin patch at 40 separate sites in right ventricle (28 Amp) and 55 separate sites in left ventricle (35 Amp) with 4 different levels of CF: (1) low (CF range of 4-13 g; median, 9.5 g); (2) moderate (15-30 g; median, 21.5 g); (3) high (34-55 g; median, 40 g); and (4) no electrode contact, 2 mm away from the endocardium. Swine were sacrificed at 2 hours after ablation, and lesion size was measured using triphenyl tetrazolium chloride staining. In 1 additional swine, COX (cytochrome c oxidase) staining was performed to examine mitochondrial activity to delineate reversible and irreversible lesion boundaries. Histological examination was performed with hematoxylin and eosin and Masson trichrome staining.
Results: Ablation lesions were well demarcated with triphenyl tetrazolium chloride staining, showing (1) a dark central zone (contraction band necrosis and hemorrhage); (2) a pale zone (no mitochondrial activity and nuclear pyknosis, indicating apoptosis zone); and a hyperstained zone by triphenyl tetrazolium chloride and COX staining (unaffected normal myocardium with preserved mitochondrial activity, consistent with reversible zone). At constant PFA current intensity, lesion depth increased significantly with increasing CF. There were no detectable lesions resulting from ablation without electrode contact.
Conclusions: Acute PFA ventricular lesions show irreversible and reversible lesion boundaries by triphenyl tetrazolium chloride staining. Electrode-tissue contact is required for effective lesion formation during PFA. At the same PFA dose, lesion depth increases significantly with increasing CF.
{"title":"Effects of Contact Force on Lesion Size During Pulsed Field Catheter Ablation: Histochemical Characterization of Ventricular Lesion Boundaries.","authors":"Hiroshi Nakagawa, Quim Castellvi, Robert Neal, Steven Girouard, Jacob Laughner, Atsushi Ikeda, Masafumi Sugawara, Yoshimori An, Ayman A Hussein, Shady Nakhla, Tyler Taigen, Jakub Srounbek, Mohamed Kanj, Pasquale Santangeli, Walid I Saliba, Antoni Ivorra, Oussama M Wazni","doi":"10.1161/CIRCEP.123.012026","DOIUrl":"10.1161/CIRCEP.123.012026","url":null,"abstract":"<p><strong>Background: </strong>Effects of contact force (CF) on lesion formation during pulsed field ablation (PFA) have not been well validated. The purpose of this study was to determine the relationship between average CF and lesion size during PFA using a swine-beating heart model.</p><p><strong>Methods: </strong>A 7F catheter with a 3.5-mm ablation electrode and CF sensor (TactiCath SE, Abbott) was connected to a PFA system (CENTAURI, Galvanize Therapeutics). In 5 closed-chest swine, biphasic PFA current was delivered between the ablation electrode and a skin patch at 40 separate sites in right ventricle (28 Amp) and 55 separate sites in left ventricle (35 Amp) with 4 different levels of CF: (1) low (CF range of 4-13 g; median, 9.5 g); (2) moderate (15-30 g; median, 21.5 g); (3) high (34-55 g; median, 40 g); and (4) no electrode contact, 2 mm away from the endocardium. Swine were sacrificed at 2 hours after ablation, and lesion size was measured using triphenyl tetrazolium chloride staining. In 1 additional swine, COX (cytochrome c oxidase) staining was performed to examine mitochondrial activity to delineate reversible and irreversible lesion boundaries. Histological examination was performed with hematoxylin and eosin and Masson trichrome staining.</p><p><strong>Results: </strong>Ablation lesions were well demarcated with triphenyl tetrazolium chloride staining, showing (1) a dark central zone (contraction band necrosis and hemorrhage); (2) a pale zone (no mitochondrial activity and nuclear pyknosis, indicating apoptosis zone); and a hyperstained zone by triphenyl tetrazolium chloride and COX staining (unaffected normal myocardium with preserved mitochondrial activity, consistent with reversible zone). At constant PFA current intensity, lesion depth increased significantly with increasing CF. There were no detectable lesions resulting from ablation without electrode contact.</p><p><strong>Conclusions: </strong>Acute PFA ventricular lesions show irreversible and reversible lesion boundaries by triphenyl tetrazolium chloride staining. Electrode-tissue contact is required for effective lesion formation during PFA. At the same PFA dose, lesion depth increases significantly with increasing CF.</p>","PeriodicalId":10319,"journal":{"name":"Circulation. Arrhythmia and electrophysiology","volume":null,"pages":null},"PeriodicalIF":8.4,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139048420","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 : 2024-01-01Epub Date: 2023-12-21DOI: 10.1161/CIRCEP.123.012387
Alexander P Benz, Guy Amit, Stuart J Connolly, Jasrita Singh, Juan G Acosta-Vélez, David Conen, Bishoy Deif, Syamkumar Divakaramenon, William F McIntyre, Viwe Mtwesi, Jason D Roberts, Jorge A Wong, Robin Zhao, Jeff S Healey
Background: Inflammation may promote atrial fibrillation (AF) recurrence after catheter ablation. This study aimed to evaluate a short-term anti-inflammatory treatment with colchicine following ablation of AF.
Methods: Patients scheduled for ablation were randomized to receive colchicine 0.6 mg twice daily or placebo for 10 days. The first dose of the study drug was administered within 4 hours before ablation. Atrial arrhythmia recurrence was defined as AF, atrial flutter, or atrial tachycardia >30 s on two 14-day Holters performed immediately and at 3 months following ablation.
Results: The modified intention-to-treat population included 199 patients (median age, 61 years; 22% female; 70% first procedure) who underwent radiofrequency (79%) or cryoballoon ablation (21%) of AF. Antiarrhythmic drugs were prescribed at discharge in 149 (75%) patients. Colchicine did not prevent atrial arrhythmia recurrence at 2 weeks (31% versus 32%; hazard ratio [HR], 0.98 [95% CI, 0.59-1.61]; P=0.92) or at 3 months following ablation (14% versus 15%; HR, 0.95 [95% CI, 0.45-2.02]; P=0.89). Postablation chest pain consistent with pericarditis was reduced with colchicine (4% versus 15%; HR, 0.26 [95% CI, 0.09-0.77]; P=0.02) and colchicine increased diarrhea (26% versus 7%; HR, 4.74 [95% CI, 1.95-11.53]; P<0.001). During a median follow-up of 1.3 years, colchicine did not reduce a composite of emergency department visit, cardiovascular hospitalization, cardioversion, or repeat ablation (29 versus 25 per 100 patient-years; HR, 1.18 [95% CI, 0.69-1.99]; P=0.55).
Conclusions: Colchicine administered for 10 days following catheter ablation did not reduce atrial arrhythmia recurrence or AF-associated clinical events, but did reduce postablation chest pain and increase diarrhea.
{"title":"Colchicine to Prevent Atrial Fibrillation Recurrence After Catheter Ablation: A Randomized, Placebo-Controlled Trial.","authors":"Alexander P Benz, Guy Amit, Stuart J Connolly, Jasrita Singh, Juan G Acosta-Vélez, David Conen, Bishoy Deif, Syamkumar Divakaramenon, William F McIntyre, Viwe Mtwesi, Jason D Roberts, Jorge A Wong, Robin Zhao, Jeff S Healey","doi":"10.1161/CIRCEP.123.012387","DOIUrl":"10.1161/CIRCEP.123.012387","url":null,"abstract":"<p><strong>Background: </strong>Inflammation may promote atrial fibrillation (AF) recurrence after catheter ablation. This study aimed to evaluate a short-term anti-inflammatory treatment with colchicine following ablation of AF.</p><p><strong>Methods: </strong>Patients scheduled for ablation were randomized to receive colchicine 0.6 mg twice daily or placebo for 10 days. The first dose of the study drug was administered within 4 hours before ablation. Atrial arrhythmia recurrence was defined as AF, atrial flutter, or atrial tachycardia >30 s on two 14-day Holters performed immediately and at 3 months following ablation.</p><p><strong>Results: </strong>The modified intention-to-treat population included 199 patients (median age, 61 years; 22% female; 70% first procedure) who underwent radiofrequency (79%) or cryoballoon ablation (21%) of AF. Antiarrhythmic drugs were prescribed at discharge in 149 (75%) patients. Colchicine did not prevent atrial arrhythmia recurrence at 2 weeks (31% versus 32%; hazard ratio [HR], 0.98 [95% CI, 0.59-1.61]; <i>P</i>=0.92) or at 3 months following ablation (14% versus 15%; HR, 0.95 [95% CI, 0.45-2.02]; <i>P</i>=0.89). Postablation chest pain consistent with pericarditis was reduced with colchicine (4% versus 15%; HR, 0.26 [95% CI, 0.09-0.77]; <i>P</i>=0.02) and colchicine increased diarrhea (26% versus 7%; HR, 4.74 [95% CI, 1.95-11.53]; <i>P</i><0.001). During a median follow-up of 1.3 years, colchicine did not reduce a composite of emergency department visit, cardiovascular hospitalization, cardioversion, or repeat ablation (29 versus 25 per 100 patient-years; HR, 1.18 [95% CI, 0.69-1.99]; <i>P</i>=0.55).</p><p><strong>Conclusions: </strong>Colchicine administered for 10 days following catheter ablation did not reduce atrial arrhythmia recurrence or AF-associated clinical events, but did reduce postablation chest pain and increase diarrhea.</p>","PeriodicalId":10319,"journal":{"name":"Circulation. Arrhythmia and electrophysiology","volume":null,"pages":null},"PeriodicalIF":8.4,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138828447","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 : 2024-01-01Epub Date: 2023-12-15DOI: 10.1161/CIRCEP.123.012072
Michael J Cutler, Lee L Eckhardt, Elizabeth S Kaufman, Elena Arbelo, Elijah R Behr, Pedro Brugada, Marina Cerrone, Lia Crotti, Carlo deAsmundis, Michael H Gollob, Minoru Horie, David T Huang, Andrew D Krahn, Barry London, Steven A Lubitz, Judith A Mackall, Koonlawee Nademanee, Marco V Perez, Vincent Probst, Dan M Roden, Frederic Sacher, Georgia Sarquella-Brugada, Melvin M Scheinman, Wataru Shimizu, Benjamin Shoemaker, Raymond W Sy, Atsuyuki Watanabe, Arthur A M Wilde
Although there is consensus on the management of patients with Brugada Syndrome with high risk for sudden cardiac arrest, asymptomatic or intermediate-risk patients present clinical management challenges. This document explores the management opinions of experts throughout the world for patients with Brugada Syndrome who do not fit guideline recommendations. Four real-world clinical scenarios were presented with commentary from small expert groups for each case. All authors voted on case-specific questions to evaluate the level of consensus among the entire group in nuanced diagnostic and management decisions relevant to each case. Points of agreement, points of controversy, and gaps in knowledge are highlighted.
{"title":"Clinical Management of Brugada Syndrome: Commentary From the Experts.","authors":"Michael J Cutler, Lee L Eckhardt, Elizabeth S Kaufman, Elena Arbelo, Elijah R Behr, Pedro Brugada, Marina Cerrone, Lia Crotti, Carlo deAsmundis, Michael H Gollob, Minoru Horie, David T Huang, Andrew D Krahn, Barry London, Steven A Lubitz, Judith A Mackall, Koonlawee Nademanee, Marco V Perez, Vincent Probst, Dan M Roden, Frederic Sacher, Georgia Sarquella-Brugada, Melvin M Scheinman, Wataru Shimizu, Benjamin Shoemaker, Raymond W Sy, Atsuyuki Watanabe, Arthur A M Wilde","doi":"10.1161/CIRCEP.123.012072","DOIUrl":"10.1161/CIRCEP.123.012072","url":null,"abstract":"<p><p>Although there is consensus on the management of patients with Brugada Syndrome with high risk for sudden cardiac arrest, asymptomatic or intermediate-risk patients present clinical management challenges. This document explores the management opinions of experts throughout the world for patients with Brugada Syndrome who do not fit guideline recommendations. Four real-world clinical scenarios were presented with commentary from small expert groups for each case. All authors voted on case-specific questions to evaluate the level of consensus among the entire group in nuanced diagnostic and management decisions relevant to each case. Points of agreement, points of controversy, and gaps in knowledge are highlighted.</p>","PeriodicalId":10319,"journal":{"name":"Circulation. Arrhythmia and electrophysiology","volume":null,"pages":null},"PeriodicalIF":9.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10824563/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138799626","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 : 2024-01-01Epub Date: 2023-12-21DOI: 10.1161/CIRCEP.123.012150
Dandan Yang, Xiaoping Wan, Neill Schwieterman, Omer Cavus, Ege Kacira, Xianyao Xu, Kenneth R Laurita, Loren E Wold, Thomas J Hund, Peter J Mohler, Isabelle Deschênes, Ji-Dong Fu
Background: MicroRNA-1 (miR1), encoded by the genes miR1-1 and miR1-2, is the most abundant microRNA in the heart and plays a critical role in heart development and physiology. Dysregulation of miR1 has been associated with various heart diseases, where a significant reduction (>75%) in miR1 expression has been observed in patient hearts with atrial fibrillation or acute myocardial infarction. However, it remains uncertain whether miR1-deficiency acts as a primary etiological factor of cardiac remodeling.
Methods: miR1-1 or miR1-2 knockout mice were crossbred to produce 75%-miR1-knockdown (75%KD; miR1-1+/-:miR1-2-/- or miR1-1-/-:miR1-2+/-) mice. Cardiac pathology of 75%KD cardiomyocytes/hearts was investigated by ECG, patch clamping, optical mapping, transcriptomic, and proteomic assays.
Results: In adult 75%KD hearts, the overall miR1 expression was reduced to ≈25% of the normal wild-type level. These adult 75%KD hearts displayed decreased ejection fraction and fractional shortening, prolonged QRS and QT intervals, and high susceptibility to arrhythmias. Adult 75%KD cardiomyocytes exhibited prolonged action potentials with impaired repolarization and excitation-contraction coupling. Comparatively, 75%KD cardiomyocytes showcased reduced Na+ current and transient outward potassium current, coupled with elevated L-type Ca2+ current, as opposed to wild-type cells. RNA sequencing and proteomics assays indicated negative regulation of cardiac muscle contraction and ion channel activities, along with a positive enrichment of smooth muscle contraction genes in 75%KD cardiomyocytes/hearts. miR1 deficiency led to dysregulation of a wide gene network, with miR1's RNA interference-direct targets influencing many indirectly regulated genes. Furthermore, after 6 weeks of bi-weekly intravenous tail-vein injection of miR1 mimics, the ejection fraction and fractional shortening of 75%KD hearts showed significant improvement but remained susceptible to arrhythmias.
Conclusions: miR1 deficiency acts as a primary etiological factor in inducing cardiac remodeling via disrupting heart regulatory homeostasis. Achieving stable and appropriate microRNA expression levels in the heart is critical for effective microRNA-based therapy in cardiovascular diseases.
{"title":"MicroRNA-1 Deficiency Is a Primary Etiological Factor Disrupting Cardiac Contractility and Electrophysiological Homeostasis.","authors":"Dandan Yang, Xiaoping Wan, Neill Schwieterman, Omer Cavus, Ege Kacira, Xianyao Xu, Kenneth R Laurita, Loren E Wold, Thomas J Hund, Peter J Mohler, Isabelle Deschênes, Ji-Dong Fu","doi":"10.1161/CIRCEP.123.012150","DOIUrl":"10.1161/CIRCEP.123.012150","url":null,"abstract":"<p><strong>Background: </strong>MicroRNA-1 (miR1), encoded by the genes <i>miR1-1</i> and <i>miR1-2</i>, is the most abundant microRNA in the heart and plays a critical role in heart development and physiology. Dysregulation of miR1 has been associated with various heart diseases, where a significant reduction (>75%) in miR1 expression has been observed in patient hearts with atrial fibrillation or acute myocardial infarction. However, it remains uncertain whether miR1-deficiency acts as a primary etiological factor of cardiac remodeling.</p><p><strong>Methods: </strong><i>miR1-1</i> or <i>miR1-2</i> knockout mice were crossbred to produce 75%-miR1-knockdown (75%KD; <i>miR1-1<sup>+/-</sup>:miR1-2<sup>-/-</sup></i> or <i>miR1-1<sup>-/-</sup>:miR1-2<sup>+/-</sup></i>) mice. Cardiac pathology of 75%KD cardiomyocytes/hearts was investigated by ECG, patch clamping, optical mapping, transcriptomic, and proteomic assays.</p><p><strong>Results: </strong>In adult 75%KD hearts, the overall miR1 expression was reduced to ≈25% of the normal wild-type level. These adult 75%KD hearts displayed decreased ejection fraction and fractional shortening, prolonged QRS and QT intervals, and high susceptibility to arrhythmias. Adult 75%KD cardiomyocytes exhibited prolonged action potentials with impaired repolarization and excitation-contraction coupling. Comparatively, 75%KD cardiomyocytes showcased reduced Na<sup>+</sup> current and transient outward potassium current, coupled with elevated L-type Ca<sup>2+</sup> current, as opposed to wild-type cells. RNA sequencing and proteomics assays indicated negative regulation of cardiac muscle contraction and ion channel activities, along with a positive enrichment of smooth muscle contraction genes in 75%KD cardiomyocytes/hearts. miR1 deficiency led to dysregulation of a wide gene network, with miR1's RNA interference-direct targets influencing many indirectly regulated genes. Furthermore, after 6 weeks of bi-weekly intravenous tail-vein injection of miR1 mimics, the ejection fraction and fractional shortening of 75%KD hearts showed significant improvement but remained susceptible to arrhythmias.</p><p><strong>Conclusions: </strong>miR1 deficiency acts as a primary etiological factor in inducing cardiac remodeling via disrupting heart regulatory homeostasis. Achieving stable and appropriate microRNA expression levels in the heart is critical for effective microRNA-based therapy in cardiovascular diseases.</p>","PeriodicalId":10319,"journal":{"name":"Circulation. Arrhythmia and electrophysiology","volume":null,"pages":null},"PeriodicalIF":8.4,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10842700/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138828448","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 : 2023-12-01Epub Date: 2023-11-11DOI: 10.1161/CIRCEP.123.012567
A John Camm, Jonathan P Piccini, Marco Alings, Paul Dorian, Gilbert Gosselin, Marie-Claude Guertin, James E Ip, Peter R Kowey, Blandine Mondésert, Fransisco J Prins, Jean-Francois Roux, Bruce S Stambler, Jwm van Eck, Nadea Al Windy, Nathalie Thermil, Silvia Shardonofsky, David B Bharucha, Denis Roy
Background: Despite chronic therapies, atrial fibrillation (AF) leads to rapid ventricular rates (RVR) often requiring intravenous treatments. Etripamil is a fast-acting, calcium-channel blocker administered intranasally affecting the atrioventricular node within minutes.
Methods: Reduction of Ventricular Rate in Patients with Atrial Fibrillation evaluated the efficacy and safety of etripamil for the reduction of ventricular rate (VR) in patients presenting urgently with AF-RVR (VR ≥110 beats per minute [bpm]), was randomized, double-blind, placebo-controlled, and conducted in Canada and the Netherlands. Patients presenting urgently with AF-RVR were randomized (1:1, etripamil nasal spray 70 mg: placebo nasal spray). The primary objective was to demonstrate the effectiveness of etripamil in reducing VR in AF-RVR within 60 minutes of treatment. Secondary objectives assessed achievement of VR <100 bpm, reduction by ≥10% and ≥20%, relief of symptoms and treatment effectiveness; adverse events; and additional measures to 360 minutes.
Results: Sixty-nine patients were randomized, 56 dosed with etripamil (n=27) or placebo (n=29). The median age was 65 years; 39% were female patients; proportions of AF types were similar between groups. The difference of mean maximum reductions in VR over 60 minutes, etripamil versus placebo, adjusting for baseline VR, was -29.91 bpm (95% CI, -40.31 to -19.52; P<0.0001). VR reductions persisted up to 150 minutes. Significantly greater proportions of patients receiving etripamil achieved VR reductions <100 bpm (with longer median duration <100 bpm), or VR reduction by ≥10% or ≥20%, versus placebo. VR reduction ≥20% occurred in 66.7% of patients in the etripamil arm and no patients in placebo. Using the Treatment Satisfaction Questionnaire for Medication-9, there was significant improvement in satisfaction on symptom relief and treatment effectiveness with etripamil versus placebo. Serious adverse events were rare; 1 patient in the etripamil arm experienced transient severe bradycardia and syncope, assessed as due to hypervagotonia.
Conclusions: Intranasal etripamil 70 mg reduced VR and improved symptom relief and treatment satisfaction. These data support further development of self-administered etripamil for the treatment of AF-RVR.
{"title":"Multicenter, Phase 2, Randomized Controlled Study of the Efficacy and Safety of Etripamil Nasal Spray for the Acute Reduction of Rapid Ventricular Rate in Patients With Symptomatic Atrial Fibrillation (ReVeRA-201).","authors":"A John Camm, Jonathan P Piccini, Marco Alings, Paul Dorian, Gilbert Gosselin, Marie-Claude Guertin, James E Ip, Peter R Kowey, Blandine Mondésert, Fransisco J Prins, Jean-Francois Roux, Bruce S Stambler, Jwm van Eck, Nadea Al Windy, Nathalie Thermil, Silvia Shardonofsky, David B Bharucha, Denis Roy","doi":"10.1161/CIRCEP.123.012567","DOIUrl":"10.1161/CIRCEP.123.012567","url":null,"abstract":"<p><strong>Background: </strong>Despite chronic therapies, atrial fibrillation (AF) leads to rapid ventricular rates (RVR) often requiring intravenous treatments. Etripamil is a fast-acting, calcium-channel blocker administered intranasally affecting the atrioventricular node within minutes.</p><p><strong>Methods: </strong>Reduction of Ventricular Rate in Patients with Atrial Fibrillation evaluated the efficacy and safety of etripamil for the reduction of ventricular rate (VR) in patients presenting urgently with AF-RVR (VR ≥110 beats per minute [bpm]), was randomized, double-blind, placebo-controlled, and conducted in Canada and the Netherlands. Patients presenting urgently with AF-RVR were randomized (1:1, etripamil nasal spray 70 mg: placebo nasal spray). The primary objective was to demonstrate the effectiveness of etripamil in reducing VR in AF-RVR within 60 minutes of treatment. Secondary objectives assessed achievement of VR <100 bpm, reduction by ≥10% and ≥20%, relief of symptoms and treatment effectiveness; adverse events; and additional measures to 360 minutes.</p><p><strong>Results: </strong>Sixty-nine patients were randomized, 56 dosed with etripamil (n=27) or placebo (n=29). The median age was 65 years; 39% were female patients; proportions of AF types were similar between groups. The difference of mean maximum reductions in VR over 60 minutes, etripamil versus placebo, adjusting for baseline VR, was -29.91 bpm (95% CI, -40.31 to -19.52; <i>P</i><0.0001). VR reductions persisted up to 150 minutes. Significantly greater proportions of patients receiving etripamil achieved VR reductions <100 bpm (with longer median duration <100 bpm), or VR reduction by ≥10% or ≥20%, versus placebo. VR reduction ≥20% occurred in 66.7% of patients in the etripamil arm and no patients in placebo. Using the Treatment Satisfaction Questionnaire for Medication-9, there was significant improvement in satisfaction on symptom relief and treatment effectiveness with etripamil versus placebo. Serious adverse events were rare; 1 patient in the etripamil arm experienced transient severe bradycardia and syncope, assessed as due to hypervagotonia.</p><p><strong>Conclusions: </strong>Intranasal etripamil 70 mg reduced VR and improved symptom relief and treatment satisfaction. These data support further development of self-administered etripamil for the treatment of AF-RVR.</p><p><strong>Registration: </strong>URL: https://www.clinicaltrials.gov; Unique Identifier: NCT04467905.</p>","PeriodicalId":10319,"journal":{"name":"Circulation. Arrhythmia and electrophysiology","volume":null,"pages":null},"PeriodicalIF":8.4,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10734780/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89717172","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 : 2023-12-01Epub Date: 2023-11-23DOI: 10.1161/CIRCEP.123.012344
Luigi Di Biase, Jacopo Marazzato, Fengwei Zou, Aung Lin, Vito Grupposo, Nilarun Chowdhuri, Jennifer Maffre, Salman Farshchi-Heydari, Tushar Sharma, Christopher Beeckler, Assaf Govari, Rahul Bhardwaj, Sanghamitra Mohanty, Andrea Natale, Hiroshi Nakagawa, Xiaodong Zhang
Background: Pulsed field ablation (PFA) has emerged as an alternative to radiofrequency ablation. However, data on focal point-by-point PFA are scarce. The aim of this study was to compare lesion durability and collateral damage between focally delivered unipolar/biphasic PFA versus radiofrequency in swine.
Methods: Eighteen swine were randomized to low-dose PFA, high-dose PFA, and radiofrequency using a multimodality generator. Radiofrequency delivered by market-available generator served as control group. A contact force-sensing catheter was used to focally deliver PFA/radiofrequency at the pulmonary veins and other predefined sites in the atria. Animals were remapped postprocedurally and 28 days postablation to test lesion durability followed by gross necroscopy and histology.
Results: All targeted sites were successfully ablated (contact force value, 13.9±4.1 g). Follow-up remapping showed persistent pulmonary vein isolation in all animals (100%) with lesion durability at nonpulmonary vein sites proven in most (98%). Regardless of the energy source used, the lesion size was similar across the study groups. Transmurality was achieved in 95% of targeted sites and 100% at pulmonary veins. On histology, PFA animals showed more mature scar formation than their radiofrequency counterpart without myocardial necrosis or inflammation. Finally, no sign of collateral damage was observed in any of the groups.
Conclusions: In a randomized preclinical study, focally delivered unipolar/biphasic PFA guided by contact force values was associated with durable lesions on chronic remapping and with mature scar formation on histology without signs of collateral injury on necroscopy. Further studies are needed to investigate the long-term feasibility of this new approach to atrial fibrillation treatment.
{"title":"Point-by-Point Pulsed Field Ablation Using a Multimodality Generator and a Contact Force-Sensing Ablation Catheter: Comparison With Radiofrequency Ablation in a Remapped Chronic Swine Heart.","authors":"Luigi Di Biase, Jacopo Marazzato, Fengwei Zou, Aung Lin, Vito Grupposo, Nilarun Chowdhuri, Jennifer Maffre, Salman Farshchi-Heydari, Tushar Sharma, Christopher Beeckler, Assaf Govari, Rahul Bhardwaj, Sanghamitra Mohanty, Andrea Natale, Hiroshi Nakagawa, Xiaodong Zhang","doi":"10.1161/CIRCEP.123.012344","DOIUrl":"10.1161/CIRCEP.123.012344","url":null,"abstract":"<p><strong>Background: </strong>Pulsed field ablation (PFA) has emerged as an alternative to radiofrequency ablation. However, data on focal point-by-point PFA are scarce. The aim of this study was to compare lesion durability and collateral damage between focally delivered unipolar/biphasic PFA versus radiofrequency in swine.</p><p><strong>Methods: </strong>Eighteen swine were randomized to low-dose PFA, high-dose PFA, and radiofrequency using a multimodality generator. Radiofrequency delivered by market-available generator served as control group. A contact force-sensing catheter was used to focally deliver PFA/radiofrequency at the pulmonary veins and other predefined sites in the atria. Animals were remapped postprocedurally and 28 days postablation to test lesion durability followed by gross necroscopy and histology.</p><p><strong>Results: </strong>All targeted sites were successfully ablated (contact force value, 13.9±4.1 g). Follow-up remapping showed persistent pulmonary vein isolation in all animals (100%) with lesion durability at nonpulmonary vein sites proven in most (98%). Regardless of the energy source used, the lesion size was similar across the study groups. Transmurality was achieved in 95% of targeted sites and 100% at pulmonary veins. On histology, PFA animals showed more mature scar formation than their radiofrequency counterpart without myocardial necrosis or inflammation. Finally, no sign of collateral damage was observed in any of the groups.</p><p><strong>Conclusions: </strong>In a randomized preclinical study, focally delivered unipolar/biphasic PFA guided by contact force values was associated with durable lesions on chronic remapping and with mature scar formation on histology without signs of collateral injury on necroscopy. Further studies are needed to investigate the long-term feasibility of this new approach to atrial fibrillation treatment.</p>","PeriodicalId":10319,"journal":{"name":"Circulation. Arrhythmia and electrophysiology","volume":null,"pages":null},"PeriodicalIF":8.4,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10734778/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138294834","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 : 2023-12-01Epub Date: 2023-11-29DOI: 10.1161/CIRCEP.123.012334
Melissa E Middeldorp, Roopinder K Sandhu, Jessica Mao, Baris Gencer, Jacqueline S Danik, Vinayaga Moorthy, Nancy R Cook, Christine M Albert
Background: Sustained forms of atrial fibrillation (AF) are associated with lower treatment success rates and poorer prognosis compared with paroxysmal AF. Yet, little is known about risk factors that predispose to persistent AF on initial presentation. Our objective was to define risk factors associated with new-onset persistent AF.
Methods: We prospectively examined the differential associations between lifestyle, clinical, and socioeconomic risk factors and AF pattern (persistent versus paroxysmal) at the time of diagnosis among 25 119 participants without a history of cardiovascular disease, AF, or cancer in the VITAL rhythm study (Vitamin D and Omega-3).
Results: During a median follow-up of 5.3 years, 900 participants developed AF and 346 (38.4%) were classified as persistent at the time of diagnosis. In multivariable competing risk models, increasing age, male sex, White race, height, weight, body mass index ≥30 kg/m2, hypertension, current or past smoking, alcohol intake ≥2 drinks/day, postcollege education, and randomized treatment with vitamin D were significantly associated with incident persistent AF. Compared with paroxysmal AF, increasing age, male sex, weight, body mass index ≥30 kg/m2, and postcollege education were more strongly associated with persistent AF in multivariable models regardless of whether interim cardiovascular disease and heart failure events were censored.
Conclusions: In a prospective cohort without baseline AF or cardiovascular disease, over one-third of AF at the time of diagnosis is persistent. Older age, male sex, postcollege education, and obesity were preferentially associated with persistent AF and represent a high-risk AF subset for population-based intervention.
{"title":"Risk Factors for the Development of New-Onset Persistent Atrial Fibrillation: Subanalysis of the VITAL Study.","authors":"Melissa E Middeldorp, Roopinder K Sandhu, Jessica Mao, Baris Gencer, Jacqueline S Danik, Vinayaga Moorthy, Nancy R Cook, Christine M Albert","doi":"10.1161/CIRCEP.123.012334","DOIUrl":"10.1161/CIRCEP.123.012334","url":null,"abstract":"<p><strong>Background: </strong>Sustained forms of atrial fibrillation (AF) are associated with lower treatment success rates and poorer prognosis compared with paroxysmal AF. Yet, little is known about risk factors that predispose to persistent AF on initial presentation. Our objective was to define risk factors associated with new-onset persistent AF.</p><p><strong>Methods: </strong>We prospectively examined the differential associations between lifestyle, clinical, and socioeconomic risk factors and AF pattern (persistent versus paroxysmal) at the time of diagnosis among 25 119 participants without a history of cardiovascular disease, AF, or cancer in the VITAL rhythm study (Vitamin D and Omega-3).</p><p><strong>Results: </strong>During a median follow-up of 5.3 years, 900 participants developed AF and 346 (38.4%) were classified as persistent at the time of diagnosis. In multivariable competing risk models, increasing age, male sex, White race, height, weight, body mass index ≥30 kg/m<sup>2</sup>, hypertension, current or past smoking, alcohol intake ≥2 drinks/day, postcollege education, and randomized treatment with vitamin D were significantly associated with incident persistent AF. Compared with paroxysmal AF, increasing age, male sex, weight, body mass index ≥30 kg/m<sup>2</sup>, and postcollege education were more strongly associated with persistent AF in multivariable models regardless of whether interim cardiovascular disease and heart failure events were censored.</p><p><strong>Conclusions: </strong>In a prospective cohort without baseline AF or cardiovascular disease, over one-third of AF at the time of diagnosis is persistent. Older age, male sex, postcollege education, and obesity were preferentially associated with persistent AF and represent a high-risk AF subset for population-based intervention.</p>","PeriodicalId":10319,"journal":{"name":"Circulation. Arrhythmia and electrophysiology","volume":null,"pages":null},"PeriodicalIF":9.1,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10852030/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138451063","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 : 2023-12-01Epub Date: 2023-11-29DOI: 10.1161/CIRCEP.123.003750
Edouard Marcoux, Deanna Sosnowski, Sandro Ninni, Martin Mackasey, Julia Cadrin-Tourigny, Jason D Roberts, Morten Salling Olesen, Diane Fatkin, Stanley Nattel
Atrial cardiomyopathy is a condition that causes electrical and contractile dysfunction of the atria, often along with structural and functional changes. Atrial cardiomyopathy most commonly occurs in conjunction with ventricular dysfunction, in which case it is difficult to discern the atrial features that are secondary to ventricular dysfunction from those that arise as a result of primary atrial abnormalities. Isolated atrial cardiomyopathy (atrial-selective cardiomyopathy [ASCM], with minimal or no ventricular function disturbance) is relatively uncommon and has most frequently been reported in association with deleterious rare genetic variants. The genes involved can affect proteins responsible for various biological functions, not necessarily limited to the heart but also involving extracardiac tissues. Atrial enlargement and atrial fibrillation are common complications of ASCM and are often the predominant clinical features. Despite progress in identifying disease-causing rare variants, an overarching understanding and approach to the molecular pathogenesis, phenotypic spectrum, and treatment of genetic ASCM is still lacking. In this review, we aim to analyze the literature relevant to genetic ASCM to understand the key features of this rather rare condition, as well as to identify distinct characteristics of ASCM and its arrhythmic complications that are related to specific genotypes. We outline the insights that have been gained using basic research models of genetic ASCM in vitro and in vivo and correlate these with patient outcomes. Finally, we provide suggestions for the future investigation of patients with genetic ASCM and improvements to basic scientific models and systems. Overall, a better understanding of the genetic underpinnings of ASCM will not only provide a better understanding of this condition but also promises to clarify our appreciation of the more commonly occurring forms of atrial cardiomyopathy associated with ventricular dysfunction.
{"title":"Genetic Atrial Cardiomyopathies: Common Features, Specific Differences, and Broader Relevance to Understanding Atrial Cardiomyopathy.","authors":"Edouard Marcoux, Deanna Sosnowski, Sandro Ninni, Martin Mackasey, Julia Cadrin-Tourigny, Jason D Roberts, Morten Salling Olesen, Diane Fatkin, Stanley Nattel","doi":"10.1161/CIRCEP.123.003750","DOIUrl":"10.1161/CIRCEP.123.003750","url":null,"abstract":"<p><p>Atrial cardiomyopathy is a condition that causes electrical and contractile dysfunction of the atria, often along with structural and functional changes. Atrial cardiomyopathy most commonly occurs in conjunction with ventricular dysfunction, in which case it is difficult to discern the atrial features that are secondary to ventricular dysfunction from those that arise as a result of primary atrial abnormalities. Isolated atrial cardiomyopathy (atrial-selective cardiomyopathy [ASCM], with minimal or no ventricular function disturbance) is relatively uncommon and has most frequently been reported in association with deleterious rare genetic variants. The genes involved can affect proteins responsible for various biological functions, not necessarily limited to the heart but also involving extracardiac tissues. Atrial enlargement and atrial fibrillation are common complications of ASCM and are often the predominant clinical features. Despite progress in identifying disease-causing rare variants, an overarching understanding and approach to the molecular pathogenesis, phenotypic spectrum, and treatment of genetic ASCM is still lacking. In this review, we aim to analyze the literature relevant to genetic ASCM to understand the key features of this rather rare condition, as well as to identify distinct characteristics of ASCM and its arrhythmic complications that are related to specific genotypes. We outline the insights that have been gained using basic research models of genetic ASCM in vitro and in vivo and correlate these with patient outcomes. Finally, we provide suggestions for the future investigation of patients with genetic ASCM and improvements to basic scientific models and systems. Overall, a better understanding of the genetic underpinnings of ASCM will not only provide a better understanding of this condition but also promises to clarify our appreciation of the more commonly occurring forms of atrial cardiomyopathy associated with ventricular dysfunction.</p>","PeriodicalId":10319,"journal":{"name":"Circulation. Arrhythmia and electrophysiology","volume":null,"pages":null},"PeriodicalIF":8.4,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138451062","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 : 2023-12-01Epub Date: 2023-11-16DOI: 10.1161/CIRCEP.123.012404
Fabrizio Assis, Harikrishna Tandri, Rushil Shah, Christopher Batich, Parag Karmarkar, Akhilesh Gonuguntla, Michele Dill, Ekin C Uzunoglu, John N Catanzaro
{"title":"Effects of Intraluminal Content on Esophageal Lesion Formation During Radiofrequency Catheter Ablation: Preliminary Data.","authors":"Fabrizio Assis, Harikrishna Tandri, Rushil Shah, Christopher Batich, Parag Karmarkar, Akhilesh Gonuguntla, Michele Dill, Ekin C Uzunoglu, John N Catanzaro","doi":"10.1161/CIRCEP.123.012404","DOIUrl":"10.1161/CIRCEP.123.012404","url":null,"abstract":"","PeriodicalId":10319,"journal":{"name":"Circulation. Arrhythmia and electrophysiology","volume":null,"pages":null},"PeriodicalIF":8.4,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134648617","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}