Circulation. Arrhythmia and electrophysiology最新文献

Background: Atrial cardiopathy often precedes atrial fibrillation (AF) and has emerged as an independent risk factor for cardiovascular outcomes. However, previous studies have been limited in size and have overlooked the right atrium.

Methods: In 51 693 UK Biobank participants without prevalent AF, we assessed biatrial volumes and emptying fraction from cardiac magnetic resonance imaging using deep learning segmentation. We evaluated associations with new-onset AF, ischemic stroke, heart failure, and dementia, conducted a genome-wide association study, and evaluated causal associations using Mendelian randomization.

Results: Among 51 693 adults, the mean (SD) age was 65 (7.7) years, and 24 584 (48%) were male. During the 4-year follow-up, 964 (1.9%) developed AF, 266 (0.5%) developed ischemic stroke, 365 (0.7%) developed heart failure, and 72 (0.1%) developed dementia. After adjustment for clinical risk factors, both left and right atrial measures were associated with new-onset AF (left atrial minimal volume; hazard ratio, 1.55 [95% CI, 1.48-1.62]), ischemic stroke, and heart failure, with stronger associations in women. Left atrial minimal volume was also associated with dementia. Our genome-wide association study identified 51 (27 novel) genetic associations with atrial measures, many of which do not overlap with established AF loci. Genetic correlations revealed that each atrium had varying correlations with cardiometabolic risk factors, and Mendelian randomization demonstrated that left atrial measures had direct causal effects on AF and stroke risk. However, the stroke associations were attenuated after accounting for AF variants.

Conclusions: In this largest assessment of biatrial structure and function to date, both left and right atrial cardiopathies were independently associated with increased risk of adverse cardiovascular events. We identified several novel genetic loci for atrial traits and observed unique genetic correlations between left and right atrial traits and cardiovascular phenotypes, providing insight into chamber-specific remodeling. Several of these measures are likely to be causal determinants of cardiovascular complications previously attributed to AF.

Background: The arrhythmogenic right ventricular cardiomyopathy (ARVC) risk calculator estimates the risk of incident sustained ventricular arrhythmia (VA) and performs well in ARVC populations meeting 2010 Task Force Criteria. However, the calculator includes no measure of left ventricular (LV) structure and function, while late gadolinium enhancement (LGE) on cardiac magnetic resonance shows promise in arrhythmic risk prediction. This study aims to evaluate whether LV LGE on cardiac magnetic resonance can further refine ARVC VA risk stratification.

Methods: Patients with definite ARVC, no prior sustained VA, and contrast-enhanced cardiac magnetic resonance at baseline were followed at 17 centers. Survival analyses were performed to assess LV LGE effect on VA prediction, and its incremental prognostic value on the risk calculator was evaluated using Cox proportional hazard models. The presence of high-risk LGE, defined as LV epicardial, transmural, or combined septal and free-wall LGE, was studied as a sensitivity analysis.

Results: Of 385 patients (39.6±15.4 years, 39.7% male, 54.0% probands), 132 (34.3%) had LV LGE on cardiac magnetic resonance, with 98 (25.5%) having a high-risk pattern. Over 3.1 [1.2-5.8] years of follow-up, 67 (17.4%) patients experienced VA. In univariable analysis, both LV LGE (hazard ratio, 1.82; P=0.014) and high-risk LV LGE (hazard ratio, 1.85; P=0.017) were associated with higher risk for VA. However, after adjusting for the ARVC calculator-estimated risk, the presence of neither LV LGE (P=0.85) nor high-risk LV LGE (P=0.87) independently predicted sustained VA. (graphic abstract).

Conclusions: While associated with the risk of VA in ARVC, LV LGE did not provide incremental prognostic value for incident VA risk prediction compared with the ARVC risk calculator.

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: 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 (Safety-and-effectiveness Clinical Evaluation of Nanosecond-pulse Ablation for Atrial Fibrillation) 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: 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 (human embryonic kidney) 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: 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 or 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.