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Calmodulinopathies are very rare genetic disorders associated with a high risk for sudden cardiac death. Disease-causing variants in 1 of the 3 identical CALM genes cause severe forms of long QT syndrome, catecholaminergic polymorphic ventricular tachycardia, or idiopathic ventricular fibrillation, and there are many unanswered questions concerning management and underlying mechanisms. What is currently known depends largely on the initial publications from the ICamR (International Calmodulinopathy Registry). However, progress is delayed because the accrual of patients in ICamR is slow. As we did long ago for long QT syndrome, this is a call for action, requesting doctors all over the world to enroll even their isolated cases in the Registry. This is the only way to obtain, for an adequate number of patients, the data necessary to define the spectrum of clinical manifestations and the genotype-phenotype correlation essential for an improved risk stratification and best therapeutic management. If you are willing to contribute, please contact us.

Aims: Traditional cardiac pacing and defibrillation devices rely on leads connected to a subcutaneous pulse generator, which can result in complications such as vascular damage, infection, or lead failure. Advances in technology have led to the development of leadless pacemakers, which combine the battery, circuitry, and electrodes into a single self-contained unit, and extravascular implantable cardioverter-defibrillators (ICDs), which position electrodes outside the vasculature. These innovations offer promising alternatives for patients requiring both defibrillation and pacing, particularly those unable or unwilling to accommodate traditional leads. However, the interactions between extravascular ICDs and leadless pacemakers remain largely unexplored and currently lack regulatory approval for combined use. This study evaluates the interactions between leadless pacemakers and extravascular ICDs to assess their simultaneous operation.

Methods and results: In-silico simulations, saline-tank experiments, and Monte Carlo simulations were conducted to evaluate device interactions, focusing on ventricular fibrillation (VF) detection during pacing conditions. Ventricular fibrillation detection was unaffected by pacing pulse widths ≤0.24 ms, with a pacing pulse-to-VF amplitude ratio of ≤2 considered safe. Wider pulse widths or higher outputs progressively increased the risk of VF undersensing. Experiments confirmed that pacing pulses ≤3 V and ≤0.24 ms minimally impacted VF detection. Proximity of device affected pacing pulse amplitude sensed by the ICD, but pacemaker orientation did not. Monte Carlo simulations indicated a 0-4% probability of undesired interactions under clinically relevant conditions.

Conclusion: Extravascular ICDs and leadless pacemakers may safely coexist, with a low observed risk of VF undersensing in our study. Further clinical studies are needed to confirm these findings.

Aims: Ablation modalities differ in their mechanisms of action, tissue specificity, and collateral effects-particularly on the cardiac autonomic nervous system. This study aimed to compare the autonomic effects of pulsed field ablation (PFA) vs. thermal ablation (TA) in patients with atrial fibrillation (AF) through a pooled analysis.

Methods and results: A systematic search of PubMed and Embase was conducted through 5 April 2025, to identify comparative studies. The primary outcome was increase in heart rate (IHR) after ablation, and the secondary outcome was increase in serum S100B (IS100B), a marker of neural injury. Eight studies involving 1007 AF patients were included (mean age: 63.39 ± 10.75 years; 36.3% female; maximum follow-up: 12 months). Baseline characteristics, including the use of antiarrhythmic drugs, were similar between the PFA and TA groups. Pooled analysis showed that PFA was associated with a significantly lower IHR compared to TA (PFA: 4.41 ± 8.86 bpm vs. TA: 10.81 ± 10.46 bpm; P < 0.00001). This difference persisted at midterm (3-6 months) and long-term (12 months) follow-up and remained consistent across age, sex, and different TA modalities (cryoballoon vs. radiofrequency). Correspondingly, the IS100B was significantly less pronounced after PFA (PFA: 33.27 ± 9.46 pg/mL vs. TA: 97.53 ± 31.88 pg/mL; P < 0.00001).

Conclusion: PFA-based pulmonary vein isolation in patients with AF results in a smaller post-procedural IHR and less S100B release, suggesting reduced neural damage and less disruption of the autonomic nervous system compared to TA. These effects are sustained through mid- to long-term follow-up and may have potential implications for patient selection and individualized ablation strategies.

Aims: There is still conflicting evidence if women with persistent atrial fibrillation (AF) profit from a pulmonary vein isolation (PVI) plus strategy. We evaluated the efficacy of a spatio-temporal dispersion-targeted ablation strategy in women from the TAILORED-AF trial.

Methods and results: In TAILORED-AF, 370 patients were randomised to either a personalised, artificial intelligence (AI)-guided tailored ablation or to PVI-only. AF substrate mapping data and 12-month ablation outcomes were compared between women and men. Overall, 21% patients were female (70.4 ± 6.9 vs. 64.5 ± 8.5 years for men, P < 0.001). While spatio-temporal dispersion extent was similar between groups, left atrial low-voltage surface area (<0.2 mV) was significantly larger in women (P < 0.01). In women, the single-procedure freedom from AF (76% vs. 50%, log-rank P < 0.001) and any atrial arrhythmia (56% vs. 38%, log-rank P < 0.05) were significantly superior to PVI alone with a tailored procedure. In the PVI-only group, the single-procedure freedom from AF (50% vs. 70%, log-rank P < 0.001) and any atrial arrhythmia (38% vs. 61%, log-rank P < 0.001) were significantly lower in women. After a tailored ablation, no significant differences were observed between women and men regarding freedom from AF (76% vs. 91%, log-rank P = 0.07) or any atrial arrhythmia (56% vs. 62%, log-rank P = 0.69) free survival.

Conclusion: Compared to men, PVI-only in women with persistent AF leads to a significantly lower freedom from atrial arrhythmia. A personalised spatio-temporal dispersion-targeted ablation strategy led to a higher rate of freedom from any atrial arrhythmia than standard PVI after a single procedure in women and comparable outcomes between women and men.

Registration identification: clinicaltrials.gov NCT04702451.

Aims: Same-day discharge (SDD) following catheter ablation for atrial fibrillation (AF) yields a promising approach to enhance patient satisfaction and reduce healthcare costs. While prior data support the safety of SDD after radiofrequency ablation, evidence following pulsed field ablation (PFA) remains limited. This sub-analysis of the admIRE trial (NCT05293639) evaluates the safety of SDD compared with overnight stays (ONS) after PFA using a variable-loop circular catheter (VLCC).

Methods and results: Baseline and procedural characteristics, safety, and effectiveness were compared between SDD and ONS groups. Primary effectiveness was defined as freedom from composite failure using Kaplan-Meier estimates. Serious adverse events (SAEs) occurring ≤7 days and ≥1 day post-index procedure were assessed. Amongst 277 patients in the admIRE trial, 119 (43.0%) completed SDD, and 158 (57.0%) stayed overnight. The SDD group included fewer patients aged ≥65 years (41.2% vs. 52.5%), shorter fluoroscopy times (4.0 vs. 8.9 min), higher first-pass isolation rates (97.5% vs. 82.9%), and fewer procedural AEs (1.7% vs. 3.8%). More procedures in the SDD group occurred in the morning (63.0% vs. 39.2%). Freedom from primary effectiveness failure was similar (SDD, 75.4% [95% CI 67.4-83.3%] vs. ONS, 74.0% [95% CI 66.4-81.5%]). No significant difference in SAE risk was observed overall [HR, 1.07 (95% CI 0.47-2.44)] or ≤7 days post-procedure [HR, 0.78 (95% CI 0.17-3.49)]. Post-procedural serious cardiac/vascular AE rates were also comparable (SDD, 2.5% vs. ONS, 1.3%).

Conclusion: SDD is feasible in a paroxysmal AF population undergoing PFA with the VLCC, demonstrating comparable safety and effectiveness outcomes with overnight hospitalization.