Circulation. Arrhythmia and electrophysiology最新文献

Background: Nanosecond pulsed field ablation, which offers potential benefits, such as reduced muscle contraction, may enable procedures to be performed under local anesthesia.To evaluate the 12-month safety and efficacy of a novel high-repetition frequency nanosecond pulsed field ablation for treating paroxysmal atrial fibrillation.

Methods: The prospective, multicenter, single-arm trial SCENA-AF study was conducted across 11 Chinese centers. Symptomatic drug-refractory patients with paroxysmal atrial fibrillation aged 18 to 80 years underwent pulmonary vein isolation using a commercial nanosecond pulsed field ablation system. The primary efficacy end point was freedom from documented atrial fibrillation, atrial flutter, or atrial tachycardia ≥30 seconds from 91 to 365 days postablation without use of class I and III antiarrhythmic drugs. The primary safety end point was freedom from device- or procedure-related death, stroke, transient ischemic attacks, or other major complications during the procedure and 12-month follow-up.

Results: Of the 166 enrolled patients who underwent the PFA procedures, 162 completed follow-up. Acute pulmonary vein isolation success was 100% for targeted veins. At 12 months, 88.49% (95% CI, 82.54%-92.50%) met the primary efficacy end point. No device- or procedure-related death, stroke, or transient ischemic attacks occurred. Notably, 92.77% of procedures were performed under local anesthesia and conscious sedation. Procedure-specific serious adverse events occurred in 2.41% of patients and were limited to access-site hematomas or pseudoaneurysms that resolved. No clinical hemolysis signs or symptoms were observed.

Conclusions: The novel high-repetition-frequency nanosecond pulsed field ablation demonstrated high 12-month efficacy and a favorable safety profile for paroxysmal atrial fibrillation treatment. The ability to perform most procedures under local anesthesia with conscious sedation, with general anesthesia rarely needed, highlights a potential advantage of this technology.

Clinical trial registration: www.clinicaltrials.gov; Unique identifier: NCT06039722.

Background: Reversible pulsed field ablation (PF_REV) can temporarily block cardiomyocyte conduction, potentially identifying critical target sites before creating definitive lesions. However, PF_REV local capture might interfere with the tachycardia mechanism. The aim of the study was to characterize the responses of nontriggered PF_REV pulses to serve as a novel clinical mapping tool in reentrant atrial flutter.

Methods: PF_REV pulses were delivered in and outside of the circuit using a 9-mm lattice-tip catheter in 30 reentrant atrial tachycardias in 26 patients. The presence of local capture and responses to PF_REV pulses was characterized.

Results: Out of 163 PF_REV pulses analyzed, 56 (34.4%) showed atrial capture and propagation. Propagated versus Nonpropagated PF_REV cohorts were compared. The coupling interval of propagated PF_REV pulses was significantly longer (195.3±69.2 msec versus 98.9±77.2 msec; P<0.001). Globally, 4 responses were observed: tachycardia termination (11.0%), stable tachycardia cycle length (TCL) prolongation (9.8%), transient irregular TCL variations (3.1%), and no change in activation sequence and TCL (76.1%). Propagation was only associated with irregular TCL variations (8.9% versus 0%, P=0.002). Tachycardia termination or TCL prolongation occurred only when PF_REV was delivered in the reentry circuit (100% specificity). Termination occurred exclusively in the critical isthmus (100% specificity regardless of propagation), and stable TCL prolongation occurred in 93.8% and 6.2% of the cases in the isthmus and outer loop, respectively (100% specificity for nonpropagated and 83.3% specificity for propagated PF_REV to localize the isthmus). Sensitivity of termination or stable TCL prolongation for identifying the critical isthmus was moderate (38.8%) and influenced by isthmus width (11.7±1.7 mm versus 22.9±2.1 mm; P<0.001). Reproducibility of PF_REV pulses, determined by consecutive pulses delivered at the same site producing identical responses, was high (82.9%).

Conclusions: PF_REV mapping is a novel, feasible, and reproducible tool for identifying critical sites in reentrant atrial tachycardia with narrow isthmuses that may be improved through optimized triggering and dose titration.

Background: A limitation of ablation for scar-related ventricular tachycardia (VT) is insufficient lesion depth to address nonendocardial substrate. Ultra-low temperature cryoablation (ULTC) at -196°C has been shown to create transmural lesions in preclinical models. Early human studies in Europe have shown safety and efficacy.

Methods: An EFS (Early Feasibility Study) was designed in collaboration with the Food and Drug Administration as a prospective, nonrandomized evaluation of the acute safety and effectiveness of ULTC ablation for scar-related VT.

Results: Twenty patients (age 63±14 years; 5% women; LVEF 36±13%; 45% ischemic and 55% nonischemic) underwent VT ablation with ULTC from September to December 2023 at 4 clinical sites. Ablation strategies included substrate modification during sinus rhythm, as well as activation and entrainment mapping when hemodynamics permitted. Mean ULTC lesions were 9.9±3.6, with a total freeze duration of 47±22 minutes. Noninducibility of the targeted VTs was observed in 13 of 14 patients with inducibility tested both pre- and postablation. There were no procedural strokes, tamponades, or deaths. One suspected cardiac perforation without tamponade was conservatively managed. One patient was excluded from the follow-up efficacy analysis due to RF use, and another lacked postacute follow-up due to death from heart failure 1 month post-procedure. Among surviving per-protocol patients, 23.7±4.3 weeks of freedom from VT and implantable cardioverter defibrillator shock were 61.1% (11/18) and 83.3% (15/18), respectively.

Conclusions: In a US EFS, ULTC therapy was safe and effective for the treatment of scar-related VT. The EFS design, in collaboration with the Food and Drug Administration, represents an important initiative to accelerate the evaluation of new medical technologies in the United States.

Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05675865.

Background: In the presence of sustained monomorphic ventricular tachycardia (VT), catheter ablation may be an option in congenital heart disease. However, the heterogeneity of underlying congenital heart disease and previous cardiac surgeries is associated with a unique and particularly complex substrate. The aim of the study was to investigate whether preprocedural 3-dimensional anatomic and substrate reconstruction based on cardiac computed tomography scan and magnetic resonance imaging could reliably identify VT substrate and ablation targets.

Methods: Consecutive patients with cardiac computed tomography or magnetic resonance imaging referred for VT ablation in 5 congenital electrophysiology centers were included. Three observers, electrophysiologists, blinded to the ablation procedure and each other, annotated potential ablation targets on 3-dimensional imaging reconstructions with a dedicated software (InHeart). Once completed, the annotations were compared between observers and with the ablation target(s) on the electroanatomical mapping generated during the procedures.

Results: Forty patients (mean age, 38±12 years; 67.5% male) underwent VT ablation, including 28 with a history of spontaneous sustained VT. VT was inducible in 97.5% of cases, with an acute success rate of ablation of 92.5%. Preprocedural imaging identified VT substrate in concordance with electroanatomical mapping in 87.5% of cases. There was a high degree of agreement between the observers. Positive interobserver agreement was complete in 65.0% of cases, moderate in 22.5%, and poor in 5.0%. Considering the total number of isthmuses identified by imaging in comparison with electroanatomical mapping, the sensitivity of imaging was 87.0%, and its positive predictive value was 77.0%.

Conclusions: In our series, 3-dimensional anatomic reconstruction enabled identification of the critical VT substrate in most patients with complex congenital heart disease, particularly those with anatomically based reentrant circuits. Substrate target can be identified by operators with good interobserver reproducibility. This approach may guide VT ablation in these challenging cases.

Background: Cardiovascular disease is the number 1 killer in industrialized countries, with sudden cardiac death due to ventricular arrhythmias representing a major component. To reduce sudden cardiac death, accurate risk prediction and development of effective preventive treatments remain major challenges. In this study, we explored the possibility of using a population-based computational modeling approach to perform virtual clinical trials for antiarrhythmic drug discovery and drug safety testing.

Methods: We developed genetically diverse populations of 1-dimensional cardiac tissue models for both normal hearts and hearts with long QT syndromes (LQT1, LQT2, and LQT3) based on matching the models to the clinically measured distributions of corrected QT intervals for each condition.

Results: Using a doubling of the L-type calcium current to mimic sympathetic stress, the population models exhibited a similar incidence of arrhythmias as observed in corresponding clinical studies for each condition. We demonstrated that the model populations (1) accurately predicted arrhythmia risk under normal and diseased conditions; (2) could be used to assess the effectiveness of a therapeutic strategy, namely shifting the steady-state inactivation curve of the L-type calcium current; and (3) accurately predicted the cardiotoxicity of a series of drugs when compared with their known clinical profiles.

Conclusions: The population-based modeling approach outlined here shows promise as a computational platform that can directly take advantage of data from human clinical studies to improve arrhythmia risk prediction, test antiarrhythmic therapies, and assess cardiotoxicity of drugs.

Background: Pathogenic SCN5A variants are associated with inherited arrhythmias such as long-QT syndrome, Brugada syndrome, and sick sinus syndrome. While Na_v1.5, an α-subunit of the cardiac sodium channel encoded by SCN5A, has been considered to function as a monomer, recent studies reveal that a reduction of sodium current in wild-type Na_v1.5 can be caused by dimerization with loss-of-function mutated Na_v1.5 through dominant-negative effects. However, the clinical significance of the dominant-negative effect remains unclear.

Method: We genetically screened a family who presented with sick sinus syndrome and sudden cardiac death. Whole-cell patch-clamp study using HEK293 cells coexpressing wild-type and variant SCN5A was performed. Channel dimerization was assessed by coimmunoprecipitation and proximity ligation assays. Also, the effects of difopein, a high-affinity inhibitor of Na_v1.5 interaction via 14-3-3 proteins, were evaluated.

Results: The proband carried compound heterozygous variants p.T1396P and p.G833R. The whole-cell mode patch-clamp techniques demonstrated that the p.T1396P showed a dominant-negative effect on the peak sodium currents (37% decrease in I_Na) and altered gating properties (5.6-mV shift in steady-state inactivation) when expressed with wild-type SCN5A. These effects were abolished by difopein. p.G833R showed no dominant-negative or coupled gating effect but still formed dimers. The proband developed earlier and more severe bradycardia than the mother, who only carries p.T1396P, suggesting that loss of coupled gating effect contributed to the severe phenotype.

Conclusions: Our findings suggest that coupled gating may be physiologically important for normal Na_v1.5 function, and its loss can exacerbate disease severity.

Background: Cardiac radioablation is emerging as a treatment modality for refractory ventricular tachycardia. This study aimed to evaluate the effects of radiation on the coronary arteries in a swine model of proton beam cardiac radioablation.

Methods: Eighteen swine underwent single-fraction 30 to 40 Gy pencil-beam scanning proton therapy targeting the left ventricle and were euthanized 12 to 40 weeks later. Treatment planning was performed without restricting the dose to the coronary arteries. The maximum point dose (D_max) to the epicardial coronary arteries was calculated. In secondary analyses, the mean (D_mean) and minimum dose received by the highest irradiated 0.01 cm³ (D_0.01) of each coronary artery were also calculated. Coronary artery segments were harvested from the D_max sites for histological analysis, and the D_max was correlated with stenosis severity.

Results: Ninety-six coronary arteries were analyzed. No stenoses were observed by computed tomography imaging preirradiation. By histological analysis posteuthanasia, 25/96 (26%) coronaries sampled at their D_max sites had ≥75% stenosis. The median D_max was 4.7 Gy for the <75% stenosis group and 29.7 Gy for the ≥75% stenosis group (P<0.001). The AUC-ROC for the association between D_max and stenosis ≥75% was 92.2%. A D_max value of 20.1 Gy best predicted stenosis ≥75%, with sensitivity 92.3% and specificity 87.1%. The AUC-ROCs for the associations of D_mean and D_0.01 with stenosis ≥75% were 84.8% and 91.6%, respectively. In histopathologic analysis, intimal hyperplasia was the most common coronary artery abnormality at the D_max sites, and it was present in 61.5% of all arteries and in 93.9% of arteries with D_max ≥20 Gy.

Conclusions: In this preclinical model of proton beam cardiac radioablation, coronary stenoses occurred in a dose-dependent manner, with D_max showing the closest correlation with stenosis ≥75%. These data provide for the first time a framework for dose constraint considerations for the coronary arteries during treatment planning for cardiac radioablation and thoracic malignancy radiation.

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.