JACC. Clinical electrophysiology最新文献

Background: Tricuspid transcatheter edge-to-edge repair (T-TEER) is an important treatment option for symptomatic severe tricuspid valve regurgitation. Interaction with a preexisting right ventricular (RV) pacing lead can result in clinically significant RV lead dysfunction over time.

Objectives: The goal of this study was to evaluate the 2-year safety and function of preexisting RV leads after T-TEER.

Methods: The Tri-LEAD (Tricuspid Right Ventricular lead entrapment in transcatheter tricuspid interventions) study was a retrospective multicenter international registry of 146 patients who underwent T-TEER with an RV lead in situ from 2015 to 2023. Primary outcome was RV lead dysfunction after T-TEER at 2 years (defined as change in RV lead function, dislodgement, or fracture) and need for intervention due to RV lead dysfunction or cardiac complication.

Results: Mean patient age was 78.1 ± 8.6 years, and 54% were male. Over a median follow-up of 557 days (Q1-Q3: 278-966 days), 10 patients (6.8%) had an impedance change >200 Ω and 2 patients (1.4%) had a threshold change ≥1 V, with no observed cases of RV lead fracture, dislodgement, cardiac structure perforation, or pacemaker-related re-interventions. T-TEER was not associated with an increased risk of the composite safety endpoint (adjusted SHR: 1.39; 95% CI: 0.64 to 3.02; P = 0.41). Over time, changes in RV lead sensing (-0.53 mV/year; 95% CI: -1.15 to 0.08; P = 0.094), impedance (-2.4 Ω/year; 95% CI: -15.4 to 10.6; P = 0.72), and threshold (-0.011 V/year; 95% CI: -0.052 to 0.031; P = 0.62) were minimal and not clinically significant.

Conclusions: T-TEER has no detrimental impact on the performance of transvenous RV leads in the short term or midterm.

Background: Clinical cardiac radiation therapy (RT-25 Gy) decreases ventricular tachycardia (VT). Nonischemic cardiomyopathy (NICM) murine studies showed improved left ventricular (LV) ejection fraction (LVEF) with low-dose RT (LDRT-5 Gy), attributed to a decrease in macrophages. However, whether LDRT reduces VT remains unknown.

Objectives: The goal of this study was to investigate the effects of LDRT on VT in NICM mice.

Methods: NICM was modeled by using long-chain acyl-CoA synthetase-1 (ACSL1^TG) mice. Post LDRT or sham treatment, ACSL1^TG mice underwent echocardiography, epicardial mapping to assess electrical properties, and norepinephrine injection to examine ventricular arrhythmias (VA). Heart tissue was collected to assess LV sympathetic innervation. To investigate the role of macrophages, macrophages in ACSL1^TG mice were depleted with anti-colony stimulating factor-1 receptor (CSF1R) antibody or vehicle treatment. LVEF, electrical properties, VA, and sympathetic innervation were measured in terminal studies as previously described.

Results: NICM mice treated with LDRT exhibited higher LVEF and lower VA. LDRT resulted in faster conduction velocity and lower activation time. LDRT mice exhibited greater sympathetic nerve density and reduced innervation heterogeneity. CSF1R mice exhibited greater LVEF. No differences were observed in VA, conduction velocity, or activation time in CSF1R mice vs vehicle-treated mice. CSF1R mice had greater nerve density, although they presented no differences in innervation heterogeneity.

Conclusions: In NICM mice, LDRT improved LV function and reduced spontaneous VA correlated with improved sympathetic nerve distribution, a known risk factor for VT. Decreasing macrophage abundance did not recapitulate the effects of LDRT on VA. Further studies are needed to validate these findings and explore antiarrhythmic mechanisms of LDRT.

Background: Sudden death and ventricular arrhythmias (VAs) remain a significant concern among patients with congenital heart disease (CHD). Although catheter ablation techniques have improved dramatically over the last decade, current evidence in this specific population is primarily derived from small retrospectvie studies.

Objectives: The aim of this study was to describe the burden and characteristics of VAs targeted by catheter ablation in CHDs, as well as associated outcomes and emerging preventive ablative strategies.

Methods: This prospective nationwide study included all patients with CHD referred for catheter ablation of a VA from 2020 to 2024 in France. The primary outcome was the rate of per-procedural acute success. Secondary outcomes included complications as well as freedom from arrhythmia recurrence.

Results: Among a total of 1,192 consecutive catheter ablation procedures, 210 (17.6%) VA catheter ablations were performed in 190 patients (mean age 43.8 ± 15.5 years; 63.8% male): ventricular tachycardia (VT) was targeted in 164 (78.1%) procedures and premature ventricular complex in 53 (25.2%) (both VT and premature ventricular complex were targeted in 7). Fourteen (6.7%) patients had a simple CHD, 161 (76.7%) a moderate CHD, and 35 (16.7%) a complex CHD. In patients with tetralogy of Fallot (n = 126), catheter ablation was performed without clinically documented VA in 46 (36.5%), mainly before transcatheter or surgical intervention. Overall, the clinical arrhythmia was successfully ablated in 182 (86.7%) patients. An acute complication was reported in 6 (2.9%) procedures, with no related death. The overall 1- and 2-year rates of freedom from recurrence were 81.5% (95% CI: 75.3%-88.4%) and 78.2% (95% CI: 71.2%-85.8%), respectively. The presence of anatomical isthmuses related to prior cardiac surgeries was associated with lower recurrence rates (HR: 0.30; 95% CI: 0.14-0.64; P < 0.001).

Conclusions: VAs represent approximately 20% of catheter ablation procedures performed in patients with CHD. This large cohort provides key insights into the effectiveness of catheter ablation and the main mechanisms of VAs in patients with CHD. The significant differences in outcomes reported depending on underlying substrate are important to consider to inform the benefit/risk assessment.

Background: Pathogenic variants in DSP cause arrhythmogenic cardiomyopathies with variable inheritance pattern. Recessive mutations underlie syndromic forms such as Carvajal syndrome, whereas dominant variants cause DSP cardiomyopathy, a left-dominant arrhythmogenic cardiomyopathy characterized by early electrical instability, inflammation, and fibrosis. The mechanisms driving these phenotypes remain poorly defined.

Objectives: The authors sought to create a clinically relevant platform to investigate disease mechanisms in Desmoplakin Cardiomyopathy.

Methods: We generated a knock-in mouse carrying the Dsp^S311A mutation, orthologous to the human pathogenic hotspot S299R. Heterozygous and homozygous mice (n ≥6/group) were longitudinally phenotyped by echocardiography, electrocardiographic telemetry, histology, and ultrastructural and molecular analyses. Moderate treadmill exercise was used as a physiological stressor. Outcomes included cardiac function, arrhythmias, fibrosis, apoptosis, inflammation, and desmosomal integrity.

Results: Homozygous Dsp^S311A/S311A mice developed early biventricular dysfunction with subepicardial necrosis, replacement fibrosis, myocardial inflammation, spontaneous arrhythmias, and cutaneous defects, recapitulating Carvajal syndrome. Heterozygous Dsp^WT/S311A mice exhibited hallmarks of dominant DSP cardiomyopathy: patchy left ventricular fibrosis, apoptosis, inflammation, and electrical instability preceding systolic impairment. Desmosomal remodeling occurred in both genotypes, with connexin-43 mislocalization evident from 1 month, whereas β-catenin nuclear translocation and reduced DSP/DSG2 protein were restricted to homozygotes. Of note, spontaneous arrhythmias and electrical instability were already present in both genotypes, temporally preceding structural remodeling. Exercise accelerated apoptosis, fibrosis, arrhythmias, and premature death.

Conclusions: This Dsp^S311A knock-in model captures key aspects of recessive and dominant DSP cardiomyopathies, uniquely combining spontaneous arrhythmias, inflammation, and extracardiac features. This model provides a unique in vivo platform to dissect DSP-related arrhythmogenic mechanisms and to test therapies aimed at preventing sudden cardiac death.