De Becker B, Derval N, Amin R
… +46 more, El Haddad M, Pambrun T, Bouyer B, Francois C, De Smet M, Channan EM, Blankoff N, Krahnefeld O, Agdirlioglu T, Minois D, Andorin A, Bessiere F, Gardey K, Sesselberg HW, Leyton-Mange JS, Marchand H, Mariottini C, Miled M, Sebag FA, Lellouche N, Andronache M, Marchese P, Rossi A, Nesti M, Herzet JM, Rodríguez Manero M, Pavlović N, Anselme F, Chaumont C, Wijnmaalen AP, Piers SRD, Waktare JEP, Najm A, Almorad A, Sousa PA, Lepièce C, Badot D, Auquier N, Efremidis M, Lian E, Maslova V, Tavernier R, Duytschaever M, Le Polain de Waroux JB, Valderrabano M, Knecht S
Circ Arrhythm Electrophysiol
· 2025 Dec · PMID 41328577
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BACKGROUND: Retrograde ethanolization of the vein of Marshall (VOM) has been identified as an adjunct technique in the treatment of persistent atrial fibrillation (AF) and left atrial tachycardia, as stated in the last c...BACKGROUND: Retrograde ethanolization of the vein of Marshall (VOM) has been identified as an adjunct technique in the treatment of persistent atrial fibrillation (AF) and left atrial tachycardia, as stated in the last consensus statement on ablation of AF. However, there is a lack of high-volume data on the technique. METHODS: Through the collection of data from worldwide centers, we performed this international survey that aims to analyze the safety and procedural characteristics of VOM ethanolization in patients referred for treatment of AF or left atrial tachycardia. RESULTS: We included 5579 patients (66 years; range, 20-93) from 26 centers, who underwent VOM ethanolization between 2008 and 2024 for persistent AF (81%), paroxysmal AF (9%), or left atrial tachycardia (10%) under deep sedation (53%) or general anesthesia (47%). A concomitant mitral isthmus line was attempted in 79% of the cases, achieving mitral isthmus block in 98% of patients. There were 0.92% of periprocedural serious adverse events, including 0.09% of peri-procedural death (5 patients). Three patients developed hemodynamic collapse immediately after VOM ethanolization, causing the death of 1 due to anaphylactic shock. One patient died following surgical drainage of pericardial effusion 3 weeks after the procedure. The 3 other deaths were not directly related to VOM ethanolization. Pericardial effusion was observed in 123 patients (2.2%) at the time of or immediately after the procedure, requiring drainage in 20 patients (0.36%) and later in 32 additional patients (0.57%), including 5 (0.09%) requiring drainage. Pacemaker implantation was required in 2 patients (0.04%), 1 for high-grade atrioventricular block and 1 for sinus node dysfunction. CONCLUSIONS: This international survey shows that VOM ethanolization is predominantly performed in patients with persistent AF. It is associated with rare but potentially life-threatening adverse events. Mitral isthmus line ablation results in a very high rate of block when performed concomitantly.
Haugaard SL, Schneider MJ, Kjeldsen ST
… +24 more, Sattler SM, Bastrup JA, Saljic A, Birk JB, Hansen C, Synnestvedt JN, van Hunnik A, Sobota V, Carstensen H, Hopster-Iversen C, Schwarzwald CC, Altintaş A, Barrès R, Jepps TA, Larsen S, Kjøbsted R, Wojtaszewski JFP, Barrado Ballestero S, Roostalu U, Herum KM, Jespersen T, Nattel S, Nissen SD, Buhl R
Circ Arrhythm Electrophysiol
· 2025 Dec · PMID 41328576
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BACKGROUND: Horses are one of the few animals that spontaneously develop atrial fibrillation (AF), making them a powerful model for studying AF mechanisms and treatment effects. Despite the initial effectiveness of treat...BACKGROUND: Horses are one of the few animals that spontaneously develop atrial fibrillation (AF), making them a powerful model for studying AF mechanisms and treatment effects. Despite the initial effectiveness of treatment in horses and humans, AF-induced atrial remodeling compromises its long-term success. Observational studies have suggested that metformin may reduce the risk of AF, but its effects on progressive AF-induced atrial remodeling have yet to be evaluated in a high-fidelity large animal model. METHODS: Here, we used a longitudinal horse model of tachypacing-induced self-sustained AF to characterize the electrical, molecular, and metabolic atrial changes over 4 months of disease, with and without metformin treatment (30 mg/kg orally, twice daily; initiated before AF induction, N=24 horses). Electrophysiological and multiomic approaches were combined with histology, echocardiography, biochemical, and mitochondrial analyses to evaluate disease progression and treatment response. RESULTS: The horse model replicated critical aspects of AF-induced atrial remodeling observed in Humans, including electrical and structural changes. Despite upregulation of metabolic genes and proteins in AF, no significant ultrastructural mitochondrial changes were detected. Metformin plasma trough levels confirmed stable therapeutic exposure. Metformin-treated horses were protected against early AF stabilization and sustained a less complex AF substrate in the right atrium after 4 months of disease. These protective effects were associated with increased right atrial activity of the metabolic regulator, AMPK (AMP-activated protein kinase), changes in metabolic pathways, and modulation of ion-channel gene expression. CONCLUSIONS: Metformin treatment conferred protection against early AF stabilization and selectively attenuated right atrial substrate complexity in a translationally relevant preclinical model. These findings support metformin as a lead molecule for AF prevention, warranting further mechanistic and clinical studies.
Rodriguez-Riascos JF, Vemulapalli HS, Prajapati P
… +9 more, Muthu P, Kim JY, Sorajja D, Shen WK, El Masry H, Sardana M, Valverde AM, Munger TM, Srivathsan K
Circ Arrhythm Electrophysiol
· 2025 Dec · PMID 41328574
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BACKGROUND: Cavotricuspid isthmus (CTI) ablation is frequently performed either as a standalone procedure or in combination with pulmonary vein isolation. With the rapid adoption of pulsed field ablation for atrial fibri...BACKGROUND: Cavotricuspid isthmus (CTI) ablation is frequently performed either as a standalone procedure or in combination with pulmonary vein isolation. With the rapid adoption of pulsed field ablation for atrial fibrillation, it is essential to delineate the utility of this modality in treating CTI-dependent atrial flutter (AFL). This study aims to evaluate the procedural and clinical outcomes of CTI ablation using pulsed field energy. METHODS: We conducted a retrospective analysis of consecutive patients who underwent pulsed field ablation for CTI-dependent AFL between January 2024 and March 2025. The primary end points were acute procedural success, periprocedural complications, and CTI-dependent AFL recurrence during follow-up. RESULTS: A total of 132 patients underwent CTI nonthermal ablation. The median age was 69.5 years, and 27.3% were female. The Farawave catheter was used in 93.9% of cases, PulseSelect in 4.5%, and Sphere-9 in 1.5%. Acute block was achieved in 99.2% of patients, although 8 required adjunctive radiofrequency ablation to complete the line. Periprocedural complications included transient ST-segment elevation in 2 patients and transient conduction disturbances in 3. During a median follow-up of 114 days (n=131), 5 patients (3.8%) experienced recurrence of typical AFL. The 6-month typical AFL-free survival estimate was 93.6%. CONCLUSIONS: Pulsed field ablation appears to be a feasible and effective strategy for CTI-dependent AFL. However, anatomic variability may limit its universal applicability with current catheter designs. Although acute procedural success is high, the long-term durability of the CTI block and its comparative efficacy versus conventional thermal ablation remain areas requiring further investigation.
Nakagawa H, Farshchi-Heydari S, Sugawara M
… +15 more, Ikeda A, Maffre J, Sharma T, Lam P, Govari A, Beeckler CT, Altmann A, Jackman WM, Franz MR, Spangler T, Hussein AA, Nakhla S, Santangeli P, Saliba WI, Wazni OM
Circ Arrhythm Electrophysiol
· 2025 Dec · PMID 41328568
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BACKGROUND: In a previous study, on pulsed-field ablation (PFA) in the swine ventricle, we found that lesion depth was described (±1 mm accuracy) by a logarithmic function of contact force (CF) and the number of PFA puls...BACKGROUND: In a previous study, on pulsed-field ablation (PFA) in the swine ventricle, we found that lesion depth was described (±1 mm accuracy) by a logarithmic function of contact force (CF) and the number of PFA pulses (PF-ablation index). This study was designed to validate prospectively whether the novel PF-ablation index would allow PFA lesions to be created at depths of 3.5, 4.5, 5.5, and 6.5 mm with high prediction accuracy in a swine-beating heart model. METHODS: A 7.5F catheter with a 3.5 mm ablation electrode and CF sensor (ThermoCool SmartTouch SF-Dual Energy) was connected to a PFA system (TRUPULSE 2). In 6 closed-chest swine, a biphasic PFA pulse was delivered between the ablation electrode and a skin patch at 123 separate ventricular sites at 5 different levels of CF (1) low (average CF: 4-15 g; median, 12 g; n=25), (2) moderate (16-30 g; median, 23 g; n=41); 3) high (31-45 g; median, 36 g; n=27), (4) very high (46-68 g; median, 52 g; n=18); or (5) no electrode contact, 1 to 2 mm from the endocardium (n=12). PFA application was terminated when the PF-ablation index reached a predicted lesion depth of 3.5 mm (27 sites), 4.5 mm (25 sites), 5.5 mm (29 sites), and 6.5 mm (30 sites). Swine were euthanized 2 hours after ablation. Lesion size was measured using triphenyl tetrazolium chloride staining. RESULTS: Predicted lesion depth by the PF-ablation index correlated well with actual lesion depthwith ±1.0 mm accuracy in 97/106 (92%) lesions and ±1.5 mm accuracy in all 106 lesions. There were no or poor relationships between intracardiac electrogram attenuation, impedance decrease, electrode temperature, and lesion size. No detectable lesions were created without electrode contact. CONCLUSIONS: A novel PF-ablation index incorporating CF and the number of PFA pulses provides high accuracy in predicting lesion depth in real-time. Intracardiac electrogram attenuation, impedance decrease, and electrode temperature are poor predictors of PFA lesion size.
Ananthan K, Chivers S, Regan W
… +9 more, de Marvao A, Vigneswaran T, Rosenthal E, Zidere V, Homfray T, Williamson C, Simpson JM, Bastiaenen R, Whitaker J
Circ Arrhythm Electrophysiol
· 2025 Dec · PMID 41328558
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BACKGROUND: Long QT syndrome (LQTS) is primarily an inherited condition associated with the risk of sudden cardiac death. Due to variable phenotypic expression, a prolonged QT interval on a 12-lead ECG is not always pres...BACKGROUND: Long QT syndrome (LQTS) is primarily an inherited condition associated with the risk of sudden cardiac death. Due to variable phenotypic expression, a prolonged QT interval on a 12-lead ECG is not always present. LQTS may present in the fetus with persistent bradycardia, including sinus bradycardia or functional 2:1 atrioventricular block. We report our experience of persistent fetal bradycardia prompting parental assessment for congenital LQTS. METHODS: From January 1, 2018 to November 1, 2023, 20 parents (20 mothers; 20 fathers) of fetuses presenting with persistent bradycardia and suspected congenital LQTS were assessed. Autoimmune-mediated atrioventricular block, diagnosed in the presence of maternal anti-Ro/anti-La antibodies, and fetuses with ventricular tachycardia were excluded. Parental ECGs were acquired in the remainder, with comprehensive evaluation, including genomic testing, performed in 12 mothers and 11 fathers. RESULTS: Among 20 fetuses, 16 had sinus bradycardia and 4 had 2:1 atrioventricular block (intermittent=2; persistent=2). Pathogenic LQTS genetic variants were found in 11 fetuses (=8; =1; =1; [calmodulin 2]=1), 9 mothers (=7; =1; =1) and 1 father (=1). Maternal corrected QT interval was higher in those with pathogenic variants compared with those who did not undergo genomic testing (456.9±11.6 versus 425.9±28.7 ms, =0.009) but <400 ms in the paternal carrier. After review, 5 mothers with pathogenic variants were commenced on β-blockers (prepartum=4; postpartum=1). Provocation testing with a treadmill exercise test led to the initiation of β-blockade postnatally in one further case. CONCLUSIONS: The first indication of parental LQTS may be persistent fetal bradycardia. This should prompt consideration of this diagnosis even with a normal maternal corrected QT interval and lead to the initiation of specific management strategies for pregnancy, delivery, and the postpartum period before the results of genomic testing are available.
Subha T, Massé S, Abderrahman Y
… +9 more, Mokhtar-Sasani G, Lai PFH, Asta J, Labos C, Bhaskaran A, Chakraborty P, Chauhan VS, Dorian P, Nanthakumar K
Circ Arrhythm Electrophysiol
· 2025 Dec · PMID 41328553
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BACKGROUND: Activation recovery interval (ARI), extracted from unipolar electrograms, serves as a practical surrogate for repolarization during experimental studies in vivo. Far-field signal contamination and low spatial...BACKGROUND: Activation recovery interval (ARI), extracted from unipolar electrograms, serves as a practical surrogate for repolarization during experimental studies in vivo. Far-field signal contamination and low spatial resolution obscure regional repolarization gradients and duration alternans detection using unipolar ARI. We hypothesized that the attenuation of far-field contamination with the principal component-referenced unipole will allow for a more accurate assessment of true local repolarization gradients and spatially assess action potential duration alternans. METHODS: Unipolar ARI and the novel method, Repol, were validated for the detection of spatial and temporal repolarization changes using simultaneous optical and electrical mapping in a rabbit Langendorff model. Repolarization changes were created using global infusion of ibutilide or pinacidil, or topical application of lidocaine. Epicardial mapping was conducted in a porcine Langendorff model following the topical application of lidocaine to investigate the spatial resolution of each method. Generalized linear models of the two methods were used to compare with optical action potential duration (APD80). RESULTS: Following the infusion of antiarrhythmic drugs, the Repol method (slope=0.90) had a slightly higher correlation to optical APD80 than the ARI method (slope=0.79). Following regional application of lidocaine, Repol was better able to localize the site of drug administration with an average 26.12% reduction as compared with 18.66% reduction in unipolar ARI (=0.0046). Additionally, temporal repolarization alternans and restitution changes assessed by Repol method tracked optical APD80 quantified time domain changes. CONCLUSIONS: Repol has higher sensitivity to local spatiotemporal repolarization heterogeneities and alternans than traditional ARI. Although ARI only correlates with uniformly distributed changes in repolarization in the entire myocardium, Repol also provided accurate regional gradient assessment and duration alternans of repolarization. These findings suggest ARI has significant far-field contamination and Repol may provide a better clinical mapping tool for spatiotemporal repolarization gradient mapping.
Lloyd MS, Reddy VY, Roberts P
… +23 more, Doshi RN, Wright DL, Boersma LVA, Friedman PA, Neuzil P, Blomström-Lundqvist C, Bongiorni MG, Burke MC, Gras D, Kutalek SP, Marijon E, Tolosana JM, Amin AK, Epstein LM, Aasbo JD, Callahan TD, Brisben AJ, West J, Matznick E, Speakman B, Bachman TN, Mont L, Knops RE
Circ Arrhythm Electrophysiol
· 2026 Jan · PMID 41231774
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BACKGROUND: MODULAR antitachycardia pacing (ATP), a multicenter, international trial, assesses a modular cardiac rhythm management system: a subcutaneous implantable cardioverter defibrillator in wireless communication w...BACKGROUND: MODULAR antitachycardia pacing (ATP), a multicenter, international trial, assesses a modular cardiac rhythm management system: a subcutaneous implantable cardioverter defibrillator in wireless communication with a leadless pacemaker (LP) capable of pace-terminating ventricular tachycardia. METHODS: Enrolees had one or more clinical risk factors for ventricular tachycardia and did not require chronic pacing. Complications included prespecified major LP system- and procedure-related complications, and any complication related to the LP, subcutaneous implantable cardioverter defibrillator, implantation, or study protocol. Survival analysis was performed to identify complication-free rates, therapy delivery, and all-cause mortality. RESULTS: The 297 patients enrolled had an ejection fraction of 35±13%, 43% secondary prevention indications, and 59% with prior ventricular arrhythmias. Of 286 patients undergoing LP implantation (100% success), 251 patients completed 12-month follow-up. Mortality rate was 6%, with none related to the implant procedure. Median follow-up duration was 23.4 months (interquartile range, 17.9-28.1). The LP major complication-free rate was 97.2%, exceeding the performance goal. The overall LP+ subcutaneous implantable cardioverter defibrillator system-related complication-free rate was 88.5%. Appropriate tachyarrhythmia-therapy (ATP+shock) rates were 14.4%, and appropriate shock rates were 8.5%. Inappropriate total tachyarrhythmia therapy was 9.5% of which 8.5% were shocks. ATP was 67.3% successful in terminating ventricular arrhythmia episodes and accelerated ventricular arrhythmias in 10.1% of episodes. Overall therapy burden (ATP+shock) was 96/100 patient-years, of which 44/100 patient-years was for shock delivery. CONCLUSIONS: One-year outcomes of the first modular pacing-defibrillator system reveal low system and LP complication rates and good ATP efficacy rates, suggesting that the modular cardiac rhythm management is a viable alternative to single-chamber implantable cardioverter defibrillators using low-energy pacing capability without the need for transvenous leads. CLINICAL TRIAL REGISTRATION:URL: https://clinicaltrials.gov/; Unique identifier: NCT04798768.
Crossley GH, Sanders P, Hansky B
… +11 more, De Filippo P, Shah MJ, Khelae SK, Richardson TD, Philippon F, Zakaib JS, Geelen T, Arias K, Maus B, Mason PK, Lead EvaluAtion for Defibrillation and Reliability Trial Investigators
Circ Arrhythm Electrophysiol
· 2026 Jan · PMID 41222500
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BACKGROUND: The LEADR (Lead Evaluation for Defibrillation and Reliability) trial evaluated the small-diameter (4.7F), lumenless, integrated bipolar OmniaSecure defibrillation lead. The trial exceeded primary safety and e...BACKGROUND: The LEADR (Lead Evaluation for Defibrillation and Reliability) trial evaluated the small-diameter (4.7F), lumenless, integrated bipolar OmniaSecure defibrillation lead. The trial exceeded primary safety and efficacy objective thresholds, demonstrating favorable efficacy at implant and a low rate of complications. Three-year term outcomes of the LEADR trial assessing the OmniaSecure lead are reported here. METHODS: The LEADR trial is a prospective, multicenter, single-arm clinical trial. Patients with an indication for de novo implantable cardioverter defibrillator/cardiac resynchronization therapy defibrillator were implanted with the OmniaSecure lead in standard right ventricle locations and followed at prespecified intervals. The lead was evaluated for safety, efficacy, and reliability through final follow-up. RESULTS: There were 643/657 patients (97.9%) successfully implanted with the OmniaSecure lead with a mean follow-up of 32.4±9.1 months (26% female, 61.9±12.9 years). Pacing capture threshold, pacing impedance, and R-wave amplitudes remained stable throughout. There was a 96.5% freedom from major study lead-related complications at 3 years. At 3 years, 22.3% of patients received appropriate therapies, that is, shock and antitachycardia pacing, with a 75.4% antitachycardia pacing efficacy. Inappropriate shock rate was 2.7% and 5.9% at 1 and 3 years, respectively. CONCLUSIONS: The final results of the LEADR trial demonstrated 3-year term safety, efficacy, and reliability of the OmniaSecure lead, emphasizing the potential utility of this lead in a wide variety of patients.
Circ Arrhythm Electrophysiol
· 2025 Nov · PMID 41159262
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BACKGROUND: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, characterized by atrial fibrosis, a crucial substrate facilitating its initiation and persistence. CKAP4 (cytoskeleton-associated prot...BACKGROUND: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, characterized by atrial fibrosis, a crucial substrate facilitating its initiation and persistence. CKAP4 (cytoskeleton-associated protein 4) has been associated with fibroblast activation; however, its involvement in atrial remodeling and AF susceptibility remains unclear. METHODS: We measured serum CKAP4 by ELISA in 189 patients with drug-refractory AF and 79 controls and then correlated these levels with left atrial scar burden assessed by 3-dimensional electroanatomic mapping. CKAP4 cell-type specificity and AF-associated regulation were evaluated in human single-cell/single-nucleus RNA-seq data sets (GSE238242 and GSE224959). CKAP4 regulation and function were examined in mice subjected to transverse aortic constriction or Ang II (angiotensin II) infusion and in neonatal rat atrial fibroblasts stimulated with Ang II using CKAP4 knockdown/overexpression. AF inducibility was tested by transesophageal burst pacing. Mechanistic studies assessed CKAP4 interactions with wingless/INT signaling pathway (WNT) 3A/WNT5A (co-immunoprecipitation and proximity ligation) and perturbed β-catenin signaling with an agonist (Wnt/β-catenin pathway agonist) or inhibitor (β-catenin/TCF pathway inhibitor) in vitro and in vivo. RESULTS: Serum CKAP4 was higher in AF than controls (<0.001) and correlated with regional and total scar burden (r=0.16-0.29; all <0.05). CKAP4 was enriched in fibroblasts and upregulated in AF in both human data sets. Transverse aortic constriction and Ang II increased atrial CKAP4 in vivo. In atrial fibroblasts, CKAP4 knockdown reduced α-Smooth Muscle Actin (α-SMA), collagen I/III, vimentin, and migration, whereas overexpression produced opposite effects. In mice, CKAP4 knockdown attenuated left atrial fibrosis and reduced AF inducibility. CKAP4 interacted with WNT3A and WNT5A and activated β-catenin signaling; SKL2001 rescued the antifibrotic/antiarrhythmic effects of CKAP4 knockdown, while β-catenin/TCF pathway inhibitor blunted CKAP4-overexpression-induced collagen synthesis and migration. CONCLUSIONS: CKAP4 promotes atrial fibrosis and increases AF vulnerability through the WNT/β-catenin signaling pathway, highlighting the CKAP4-WNT/β-catenin axis as a promising therapeutic target to attenuate atrial structural remodeling in AF.
Multifocal ectopic Purkinje-related premature contractions syndrome presents as a rare cardiac disorder characterized by frequent multifocal ectopic ventricular beats with narrow QRS complexes, originating from various e...Multifocal ectopic Purkinje-related premature contractions syndrome presents as a rare cardiac disorder characterized by frequent multifocal ectopic ventricular beats with narrow QRS complexes, originating from various ectopic foci along the fascicular-Purkinje system. It is characterized by mutations in the gene, inducing a gain-of-function in the human cardiac voltage-gated Na channel (Na1.5), which causes an alteration in the action potentials of the cardiomyocytes. The syndrome was initially delineated in 2012 by Laurent et al in 3 Dutch families, subsequently garnering recognition through several reported cases worldwide. Clinically, it often manifests with a familial predisposition to other arrhythmogenic cardiac diseases, alongside symptoms such as palpitations and syncope. A key diagnostic hallmark is the high daily burden of multifocal premature ventricular contractions observed on 24-hour dynamic ECG, with evidence of repetitive ventricular arrhythmias. This can potentially induce a reversible form of left ventricular dilation with systolic dysfunction, known as premature ventricular contraction-induced cardiomyopathy. Diagnosis may be challenging, requiring exclusion of the most frequent causes of ventricular arrhythmias first. The disappearance of arrhythmias during a stress test and the inefficacy of catheter ablation procedures may serve as additional elements to bolster the suspicion of multifocal ectopic Purkinje-related premature contractions syndrome. Genetic testing and electrophysiological studies are pivotal in confirming the diagnosis. Therapeutic management of this syndrome primarily involves medical therapy with class I antiarrhythmic drugs, such as flecainide and quinidine, which may reduce ventricular arrhythmias and associated symptoms. In this systematic review, our aim was to provide an exhaustive insight into the genetic basis, diagnosis, and treatment strategies for this intriguing yet relatively underexplored syndrome.
Al-Ahmad A, Hincapie-Tabares D, Zei PC
… +28 more, Natale A, Kessler D, Gallinghouse J, Bode W, Osorio J, Dukes JW, Eckart R, Amin A, Vivas Y, Mora L, Thosani A, Silverstein J, Rajendra A, Morales G, Manogue M, Donnelly J, Cuoco F, Sidney D, Brewer R, Meyers J, Metzl MD, Mohanty G, Rehorn M, Dominic P, Day JD, Nannapaneni N, Costello J, DISRUPT-AF Investigators
BACKGROUND: Pulsed field ablation (PFA) has been available in Europe since 2021. In the United States, PFA became commercially available in 2024, and practice patterns are expected to differ from those in Europe. The obj...BACKGROUND: Pulsed field ablation (PFA) has been available in Europe since 2021. In the United States, PFA became commercially available in 2024, and practice patterns are expected to differ from those in Europe. The objective of this study was to describe acute procedural efficiency and safety outcomes, clinical workflow patterns, and the physician learning curve associated with PFA for paroxysmal and nonparoxysmal atrial fibrillation in the first US real-world registry. METHODS: DISRUPT-AF (A Registry Based Collaborative to Measure Efficiency, Effectiveness, and Safety of Farapulse PFA Technology for AF) is a prospective, multicenter registry capturing patient-level data on first-time PFA procedures for paroxysmal atrial fibrillation and nonparoxysmal atrial fibrillation using the pentaspline catheter. Patient baseline characteristics and acute procedural efficiency and safety outcomes were collected. Physicians' learning curve analyses were assessed by categorizing experience levels as 1 to 3, 4 to 10, and >11 procedures. RESULTS: A total of 1076 patients were included; 80.9% of the cases involved ablation beyond the pulmonary veins. Most procedures were performed under general anesthesia (90.2%) using electroanatomic mapping (94.8%). The mean procedural time was 66.64±28.36 minutes. The median fluoroscopy time was 6.17 (0-11.6) minutes, with 25.3% of cases performed using a zero-fluoroscopy approach and 31% utilizing a low-fluoroscopy approach (<2 minutes). The overall procedure-related complication rate was low (1.7%), driven primarily by vascular access complications requiring intervention or transfusion. Procedural efficiency improved with operator experience, evidenced by a reduction in both procedural and fluoroscopy times. CONCLUSIONS: Initial US experience with the pentaspline PFA catheter demonstrated key differences from previously reported European workflows, including higher use of general anesthesia and electroanatomic mapping. Physician learning curve analysis indicated rapid adoption, with improvements in procedural efficiency and consistent safety with operator experience.
Circ Arrhythm Electrophysiol
· 2025 Nov · PMID 41090224
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BACKGROUND: BMP10 (bone morphogenetic protein 10) is a ligand of the TGF (transforming growth factor) β superfamily secreted mainly by atrial cardiomyocytes. Elevated BMP10 blood concentrations predict atrial fibrillatio...BACKGROUND: BMP10 (bone morphogenetic protein 10) is a ligand of the TGF (transforming growth factor) β superfamily secreted mainly by atrial cardiomyocytes. Elevated BMP10 blood concentrations predict atrial fibrillation (AF), AF recurrence after ablation, and AF-related cardiovascular complications like stroke. The conditions increasing BMP10 secretion and the downstream effects of BMP10 in cardiomyocytes are poorly understood. We assessed BMP10 secretion dynamics and BMP10 effects in a human 3-dimensional model of atrial and ventricular engineered heart tissue (EHT). METHODS: Cardiomyocytes (atrial and ventricular) differentiated from human induced pluripotent stem cells were cast into a fibrin-matrix to generate EHT. Atrial EHTs were optogenetically paced (3-5 Hz) or maintained at intrinsic beating rate for 24 hours up to 15 days. Release of BMP10 and other cardiac biomarkers from EHT was quantified. BMP10 plasma concentrations were compared between 1370 patients with different atrial rhythms at blood draw. Additionally, ventricular EHTs were exposed to BMP10 for 10 days. RESULTS: Atrial but not ventricular EHT released BMP10 within 48 hours of culture. High-rate optogenetic pacing increased atrial EHT BMP10 release by ≈3-fold after a latency of at least 24 hours post initiation of pacing. BMP10 plasma concentrations were elevated in patients with documented AF compared with sinus rhythm and even higher in patients with current AF. BMP10 induced upregulation of TGFβ pathway transcripts, increased expression of genes related to AF and heart failure, including and , and increased relative contraction times in ventricular EHTs. CONCLUSIONS: High atrial rates elevate BMP10 expression and release, and higher plasma concentrations of BMP10 are observed in patients with active AF. BMP10 exposure induces transcriptomic changes linked to AF and heart failure in ventricular EHT. These findings support BMP10 as a biomarker and potential mediator of AF-related remodeling and tachycardiomyopathy.
Cauti FM, Rossi P, Magnocavallo M
… +20 more, Polselli M, Martini N, Fioravanti F, Tanese N, Della Rocca DG, Spiriti G, Rampa L, Calore F, Donadello G, Del Greco A, Bondavalli B, Bisceglia C, Bisignani A, Iaia L, Scalisi G, Peretto G, Barengo A, Piccirillo G, Bianchi S, Della Bella P
Circ Arrhythm Electrophysiol
· 2025 Nov · PMID 41090217
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BACKGROUND: Ventricular electrogram duration map (VEDUM) is a new approach for the identification of the arrhythmogenic substrate critical for ventricular tachycardia (VT), and it is based on the evaluation of the prolon...BACKGROUND: Ventricular electrogram duration map (VEDUM) is a new approach for the identification of the arrhythmogenic substrate critical for ventricular tachycardia (VT), and it is based on the evaluation of the prolonged bipolar electrograms. Our aim is to evaluate the prognostic role of the VEDUM area in patients with VT and ischemic cardiomyopathy. METHODS: We enrolled all patients with ischemic cardiomyopathy who underwent VT ablation in 2 different centers. After isthmus transection for VT inducible, the procedure was aimed at noninducibility of any VT plus substrate modification. For each patient, we retrospectively analyzed the amount of the VEDUM area covered during catheter ablation. The primary outcome included any recurrence of sustained VT. RESULTS: Seventy-one patients (mean age: 69.9±8.9 years; males 93%) were enrolled. The mean size of the VEDUM area was 14.6±10.3 cm, and it was visualized in a low voltage area in 65 (91.6%) patients. A deceleration zone and late potentials were recorded inside the VEDUM area in 71.8% and 73.2%, respectively. During a mean follow-up of 24.4±13.9 months, the primary outcome occurred in 18 (25.4%) cases; the arrhythmia free-survival was significantly lower in patients with ablation of at least 75% of the VEDUM area (VEDUM <50%: 57.5%; 50% <VEDUM <75%: 76%; VEDUM >75%: 89.5%; log-rank value: 0.047). The ablation of at least 50% of the VEDUM area (hazard ratio, 0.374 [0.147-0.947]; value, 0.038) and the VT inducibility (hazard ratio, 4.087 [1.341-12.450]; value, 0.013) represented the only predictors of VT recurrence. CONCLUSIONS: VEDUM area ablation represented a new target for catheter ablation of VT in patients with ischemic cardiomyopathy.