Circulation. Arrhythmia and electrophysiology最新文献

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 PITX2 and NPPB, 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.

Background: Recurrence of atrial arrhythmias remains a significant challenge following catheter ablation for atrial fibrillation. The potential role of semaglutide in reducing atrial arrhythmia recurrence postablation is unclear.

Methods: A consecutive sample of 437 patients with a body mass index ≥24 kg/m² and type 2 diabetes who underwent their first atrial fibrillation ablation procedure between January 2022 and March 2024 were enrolled. Participants were divided into a semaglutide group and a control group based on patient preference. The primary outcome was the freedom from atrial arrhythmia recurrence during the 12-month follow-up period after the 3-month blanking period postablation.

Results: Of the 437 enrolled patients, 158 opted for semaglutide therapy and 279 declined. At baseline, the semaglutide group had higher body mass index (27.5 [2.2] versus 27.0 [2.4]; P=0.038) and glycated hemoglobin levels (8.0 [1.0] versus 7.6 [1.1]; P<0.001) compared with controls. During the 12-month follow-up, the semaglutide group showed a higher event-free rate for recurrent atrial arrhythmias (hazard ratio, 0.68 [95% CI, 0.49-0.95]; P=0.030), greater weight loss (-8.2% [3.2] versus -4.6% [2.9]; P<0.001), and larger reductions in glycated hemoglobin (-1.3% [0.8] versus -0.6% [0.8]; P<0.001).

Conclusions: Semaglutide treatment following catheter ablation for atrial fibrillation is associated with a lower rate of atrial arrhythmia recurrence over 12 months and may lead to improvements in weight and glycated hemoglobin levels.

Background: Radiofrequency catheter ablation (RFCA) of ventricular tachycardia (VT) in arrhythmogenic right ventricular cardiomyopathy is safe and reduces ventricular arrhythmia burden. Previous studies included adult patients, and data on pediatric patients are scarce. The objective of our study was to report on the safety and efficacy of RFCA in pediatric arrhythmogenic right ventricular cardiomyopathy.

Methods: Fifteen patients who fulfilled the 2010 arrhythmogenic right ventricular cardiomyopathy task force criteria, clinically presented before the age of 18, and underwent VT RFCA procedures at ≤21 years old were included. Baseline characteristics, genotypic and phenotypic data, and ablation outcomes were collected.

Results: The mean age at symptom onset was 15.5±1.6 years, and at the index procedure was 18.1±2 years, with 73% of the patients being male. Pathogenic mutation in desmosomal genes was detected in 87%. First presentation symptoms included palpitations (33%), syncope (27%), sustained VT (27%), and sudden cardiac arrest (13%). ECG repolarization abnormalities were present in 93% and 40% were reported to be athletes. In the index RFCA procedure, sustained monomorphic VT was induced in 60%. Electroanatomic mapping showed 100% basal RV epicardial substrate and 54% endocardial low voltage/scar. Repeat VT ablation was required in 80% over a mean follow-up of 16.4 months. The median number of procedures was 2 (interquartile range, 2-4), with sustained VT-free survival of 73% over a mean follow-up duration of 21.4 months. No acute periprocedural complications occurred. Bilateral cardiac sympathetic denervation due to recurrent ventricular arrhythmia was performed in 27%. Eventually, 2 patients (13%) developed advanced heart failure and underwent heart transplantation.

Conclusions: Pediatric arrhythmogenic right ventricular cardiomyopathy RFCA is safe, but early recurrences are common, requiring repeat ablations and sometimes bilateral cardiac sympathetic denervation. The substrate is mostly epicardial with preserved endocardial voltage. VT free survival is 73% after multiple procedures. Progressive heart failure requiring transplantation occurred in 13% within 2 decades of initial presentation.

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 cm², 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% 75%: 89.5%; log-rank P value: 0.047). The ablation of at least 50% of the VEDUM area (hazard ratio, 0.374 [0.147-0.947]; P value, 0.038) and the VT inducibility (hazard ratio, 4.087 [1.341-12.450]; P 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.

Background: In nonischemic cardiomyopathy, mitochondrial Ca²⁺ handling is involved in arrhythmogenesis by modulating diastolic sarcoplasmic reticulum (SR) Ca²⁺ release. Recently, it has been reported that lysosomal Ca²⁺ release can trigger an SR Ca²⁺ release. We investigated whether lysosomal Ca²⁺ flux through the TRPML1 (transient receptor potential mucolipin 1) channel could contribute to ischemic cardiomyopathy-related arrhythmia by causing diastolic SR Ca²⁺ release.

Methods: Ischemic cardiomyopathy was induced in wild-type C57BL/6J and TRPML1 heterozygous knockdown (TRPML1±) mice by ligating the left anterior descending coronary artery. Mice were studied at 3 weeks after myocardial infarction (MI).

Results: After MI, the lysosomal-restricted TRPML1 Ca²⁺ release channel was significantly increased in human patients with ischemic or nonischemic cardiomyopathy. TRPML1, but not the TPC2 (2-pore channel 2), was significantly upregulated by 85% in the mouse MI border zone and by 55% in a remote zone. Lysosomal number and approximation to the SR were increased after MI. Lysosomal Ca²⁺ release was substantially upregulated in MI mouse cardiomyocytes compared with sham cardiomyocytes. The action potential duration was prolonged, and arrhythmogenic diastolic SR Ca²⁺ release was increased in the cardiomyocytes isolated from MI mice. Blocking TRPML1 reduced action potential duration prolongation and depressed early and delayed afterdepolarizations in cardiomyocytes isolated from MI mice, while the TRPML1 agonist increased TRPML1-dependent cellular triggered activity. A TRPML1 antagonist could inhibit induced ventricular fibrillation in MI mice. Consistent with that result, genetic knockdown of TRPML1 could inhibit arrhythmic risk after MI. The effects of TRPML1-targeted drugs were not seen in control cardiomyocytes.

Conclusions: Lysosomes contribute to arrhythmic risk after MI because of increased number, proximity to the SR, and induction of diastolic SR Ca²⁺ release mediated by TRPML1-dependent lysosomal Ca²⁺ release.

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 SCN5A gene, inducing a gain-of-function in the human cardiac voltage-gated Na⁺ channel (Na_v1.5), 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.

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.

Background: Despite advances in endocardial catheter ablation (ECA) for persistent atrial fibrillation (PersAF), undertreatment persists, especially in ECA nonresponders and in longstanding PersAF (LSPersAF), with disappointing ablation results. These patients need effective clinical treatment options.

Methods: The DEEP (Dual Epicardial and Endocardial Procedure) was a prospective, multicenter, single-arm, investigational device exemption trial to establish the safety and effectiveness of a combined epicardial/endocardial ablation procedure with left atrial appendage exclusion for PersAF/LSPersAF. Eligibility included age 18 to 75 years; symptomatic PersAF/LSPersAF refractory to ≥1 Class I/III antiarrhythmic drug; and ≤2 previous failed ECAs. Two-stage hybrid ablation included ECA performed at 91 to 121 days after the epicardial first stage (including left atrial appendage exclusion), followed by a 90-day blanking and 90-day antiarrhythmic drug optimization period. Primary effectiveness was defined as freedom from documented atrial fibrillation/atrial flutter/atrial tachycardia episodes >30 seconds through the 12-month follow-up, absent Class I/III antiarrhythmic drugs, except previously failed antiarrhythmic drugs at doses not exceeding those previously failed. Primary safety was defined as a composite of device/procedure-related serious adverse events within 30 days of epicardial ablation and 7 days of ECA.

Results: Ninety patients enrolled from February 2015 to December 2020; 83.3% (75/90) were male and mean±SD age was 63.4±7.7 years. AF classification was 83.3% (75/90) PersAF/16.7% (15/90) LSPersAF, and 47.8% (43/90) had prior ECA. The composite serious adverse events rate was 6.7% (6/90 [95% CI, 2.5%-13.9%]; P<0.001 versus safety goal), including 3 patients experiencing serious adverse events within 30 days of the epicardial procedure and 3 patients within 7 days of the endocardial procedure, all of whom were anticoagulated at the time of the event. Primary effectiveness through 12 months was 71.8% (61/85 [95% CI, 62.2%-81.3%]; P=0.0134 versus performance goal) and was 62.4% (53/85 [95% CI, 52.1%-72.7%]) through 2 years.

Conclusions: A collaborative hybrid ablation approach to treating PersAF/LSPersAF is safe and effective.

Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02393885.