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Introduction: Ventricular tachycardia (VT) in patients with structural heart disease can be life-threatening and may persist despite antiarrhythmic therapy and catheter ablation. When standard treatments are ineffective or contraindicated, stereotactic arrhythmia radioablation (STAR) has emerged as a non-invasive salvage option.

Methods: This prospective, single-center study included 19 patients with structural heart disease and recurrent VT unresponsive to conventional therapy and who were ineligible for ablation. Patients were selected by a multidisciplinary team and underwent cardiac CT and electroanatomic mapping for substrate characterization. STAR was delivered in a single 25Gy fraction using volumetric modulated arc therapy. Primary endpoints included safety (adverse events within 12 months) and efficacy (reduction in VT burden, assessed by ICD-recorded anti-tachycardia pacing [ATP] and shocks).

Results: During a median follow-up of 14 months [IQR 9-15], STAR was associated with a significant reduction in ICD therapies, with an average decrease of 81%. Mean ATP interventions/month dropped from 4.5±6.5 to 0.8±2.3 (p=0.029), and total ICD therapies/month decreased from 4.8±7.0 to 0.9±2.5 (p=0.032). Mild pulmonary injury and pericardial effusion occurred in 22.2% of patients. Most cases were asymptomatic; one patient (5.5%) required non-urgent pericardiocentesis. No significant changes in left ventricular function, valvular status, or coronary artery disease progression (assessed by CAD-RADS and PCAT analysis) were observed. One-year mortality was 33.3%; no deaths were directly attributable to STAR.

Conclusion: STAR shows promise as a safe, noninvasive option for patients with refractory VT and advanced cardiomyopathy. Larger multicenter studies are needed to confirm long-term outcomes and better define its clinical role.

The KCNH2 (hERG) gene encodes the Kv11.1 protein, the pore-forming subunit of the rapid delayed rectifier potassium channel, which plays a key role in cardiac repolarization. We aimed to investigate the function of two Kv11.1 variants in trans, S1021Qfs*98 and A228V, identified in a patient suffering from idiopathic ventricular fibrillation (VF). A detailed clinical and genetic investigation was followed by functional analysis using the whole-cell patch clamp technique, western blot, and mathematical simulations in a human ventricular cell model. In comparison with WT, the current was decreased by 69.5 and 69.2 % in S1021Qfs*98 and S1021Qfs*98/A228V, respectively, which agreed well with a significant decrease in the expression of S1021Qfs*98 channels, but no differences were observed in A228V. The voltage dependence of activation and inactivation and the time course of activation and deactivation remained unchanged. Minor changes were observed in the time course of inactivation and recovery from inactivation in S1021Qfs*98 and S1021Qfs*98/A228V. Arrhythmogenesis based on early afterdepolarizations (EADs) at rest, provoked by hypokalemia, and during β-adrenergic stimulation was suggested by simulations in a human ventricular cell model. To conclude, A228V is a benign variant, whereas S1021Qfs*98 exhibits a loss-of-function defect and dominant negativity. EADs-related arrhythmogenesis was predicted, which explains the pathogenic phenotype of the proband carrying both these variants and experiencing repetitive VF episodes. Based on the findings, we reclassify S1021Qfs*98 as a pathogenic, LQT2-associated variant. The data highlight the importance of functional analysis for the correct management of patients with idiopathic VF and genetic variants.

Aims: A personalized pulmonary vein isolation (PVI) approach aimed at ablation index (AI) titration according to multidetector computed tomography-derived left atrial wall thickness (LAWT) maps reported high effectiveness and efficiency outcomes for persistent atrial fibrillation (PeAF) ablation. To date, no randomized trials have compared this approach with the standard CLOSE protocol. This non-inferiority randomized controlled trial sought to compare a LAWT-guided PVI with CLOSE protocol-based for PeAF (NCT05396534).

Methods and results: Consecutive patients referred for first-time PeAF ablation were randomized on a 1:1 basis. In the by-LAWT arm, the AI was titrated according to local LAWT, and the ablation line was personalized to avoid the thickest regions at the pulmonary vein antrum. In the CLOSE arm, LAWT information was not available to the operator; the ablation was performed according to the CLOSE study settings: AI is ≥400 at the posterior wall and ≥550 at the anterior wall. Primary endpoint was freedom from atrial arrhythmias recurrence. Secondary endpoints were the major complication rate, procedure time, radiofrequency time, and first-pass PVI rate. One hundred fifty-six patients were included. At 12 month follow-up, no significant difference occurred in atrial arrhythmia-free survival between groups (P = 0.50). In the by-LAWT group, a significant reduction in procedure time (60.5 vs. 80.0 min; P < 0.01) and RF time (14.4 vs. 28.6 min; P < 0.01) was observed. No difference was observed regarding first-pass PVI (P = 0.72) and the major complication rate (P = 0.99).

Conclusions: The PeAF-by-LAWT trial is the first prospective randomized study to demonstrate that a personalized LAWT-guided PVI for PeAF ablation is non-inferior to the standard CLOSE protocol in terms of arrhythmia-free survival while significantly improving procedural efficiency. The study was not powered to detect differences in safety outcomes.

Atrial fibrillation (AF) is a growing unmet medical need. To reduce its impact on patients' lives, improvements in stroke prevention therapy, treatment of concomitant conditions, and rhythm control therapy are actively developed: Innovations in anti-thrombotic agents, new anti-arrhythmic drugs (AADs), and novel interventional rhythm control therapies emerge alongside AF-reducing effects of general cardiometabolic therapies. Simple risk scores are slowly replaced by personalized AF risk estimation using quantifiable features. These developments were discussed by over 80 experts from academia and industry during the 10th Atrial Fibrillation NETwork /European Heart Rhythm Association consensus conference from 5 to 7 May 2025. The emerging consensus, described here, is multi-domain therapy combining stroke prevention, rhythm control, and therapy of concomitant cardiovascular conditions. This combines anti-coagulants, AADs, and AF ablation with old and new cardiometabolic drugs that can reduce AF risk, AF burden, and AF-related complications at scale. The paper furthermore describes quantitative traits that may enable a shift towards risk-driven therapy based on AF phenotypes. These can enable adjusted therapy strategies that are safe, accessible, and patient-centred. Applying modern data science and artificial intelligence methods to quantitative phenotypic and genetic features can further improve risk estimation and personalized therapy selection. At the same time, translational and clinical research into reversing the drivers of AF and into improved stroke prevention through new drugs and through combination therapies is needed. Together, these efforts offer pathways towards personalized, patient-centred, multi-modal, and accessible AF management that integrates rhythm control, stroke prevention, and therapy of concomitant conditions to bridge today's practical needs with tomorrow's therapeutic innovation.

Aims: Multimorbidity frequently coexists with atrial fibrillation (AF) and complicates treatment decisions. While current guidelines offer selective recommendations for catheter ablation in this group, evidence remains limited. This study aimed to evaluate whether comorbidity burden modifies the effectiveness of catheter ablation vs. antiarrhythmic drug therapy.

Methods and results: In this post hoc analysis of the CABANA trial, patients were stratified by overall comorbidity burden using a data-driven threshold based on the distribution of 15 pre-specified conditions. The primary outcome was a composite of all-cause mortality, disabling stroke, serious bleeding, or cardiac arrest. Secondary outcomes included cardiovascular hospitalization and a composite of all-cause mortality or cardiovascular hospitalization. Additional outcomes included AF recurrence and AF-related quality of life in a sub-cohort. Of 2204 patients, 736 had high comorbidity burden {≥4 conditions, based on a data-driven threshold; median age 68.0 [interquartile range (IQR): 63.0-73.0], 67.1% male} and 1468 had low burden [median age 67.0 (IQR: 61.0-71.0), 60.7% male]. Over a median follow-up of 3.9 years (IQR: 2.4-5.1), for the primary outcome, the adjusted hazard ratio for catheter ablation vs. drug therapy was 0.62 [95% confidence interval (CI): 0.42-0.93] in patients with high comorbidity burden and 1.16 (95% CI: 0.76-1.77) in those with low burden (interaction P = 0.038). Secondary outcomes also tended to favour ablation in the high comorbidity burden group. Moreover, catheter ablation significantly reduced AF recurrence, with relative risk reductions of 49% and 40% in the low- and high-burden groups, respectively. Furthermore, catheter ablation improved AF-related quality of life in both comorbidity groups, with more sustained and pronounced benefits over time in patients with high comorbidity burden.

Conclusion: Catheter ablation was associated with more favourable clinical outcomes in AF patients with high comorbidity burden, which support broader consideration of ablation in this population, though prospective trials are needed to confirm and guide clinical decision-making in personalized rhythm management.

Pre-registered clinical trial number: NCT00911508.

Aims: To evaluate in patients with heart failure with reduced ejection fraction (HFrEF) the association between patient characteristics and likelihood of receiving cardiac resynchronization therapy (CRT), as well as between CRT and clinical outcomes, according to comorbid atrial fibrillation (AF).

Methods and results: Patients in the Swedish Heart Failure (HF) Registry who met the guidelines' recommendation for CRT between 2014 and 2022 were included. The primary endpoint was the composite of time to first HF hospitalization or cardiovascular (CV) death. Secondary endpoints were its individual components, all-cause death, and the total number of HF hospitalizations. Out of 3530 patients with HFrEF and an indication for CRT, 24.7% received a CRT. A history of or concomitant AF were observed in 51.6% of patients. AF was not associated with the likelihood of receiving a CRT, and the patient characteristics independently associated with CRT were consistent regardless of AF, except for CRT being less likely implanted in patients with valvular disease without AF, and more likely among those with AF and university (vs. compulsory) education. Regardless of AF, CRT use was associated with a lower adjusted risk of CV death/first HF hospitalization [hazard ratio (HR): 0.71, 95% confidence interval (CI) 0.64-0.79], of its individual components, and of all-cause death (HR: 0.72, 95% CI 0.64-0.81), but not with total number of HF hospitalizations.

Conclusion: A diagnosis of AF was not associated with the likelihood of receiving CRT in real-world HF care, nor did it affect the association between CRT and lower risk of clinical outcomes.

Aims: Automated QTc measurements from commercial ECG systems often diverge from expert readings. We developed QTcNet, a deep learning model trained and validated on multiple large ECG datasets to improve automated QTc measurement accuracy.

Methods and results: QTcNet employs a regression-based convolutional neural network architecture. It was trained on 120 300 algorithm-labelled ECGs (60 150 from an internal hospital cohort and 60 150 from the MIMIC-IV dataset) after correction for a vendor-specific +15 ms bias. Performance was evaluated against expert QTc measurements in three independent datasets: PTB Diagnostic ECG Database (n = 100 ECGs in validation set), QTcMS (n = 210), and ECGRDVQ (n = 5219). The effect of fine-tuning on cardiologist-annotated ECGs was tested in the PTB database (n = 449 in fine-tuning set). Model explainability analyses were performed with Integrated Gradient maps. QTcNet reduced cross-cohort mean absolute error (MAE) from 23.4 to 13.4 ms and root mean square error (RMSE) from 40.1 to 22.1 ms, almost halving large (>50 ms) outliers. Fine-tuning only reduced errors in the PTB dataset but did not improve cross-cohort performance. Integrated Gradient maps confirmed that the model concentrated on QRS onset and T wave offset, supporting physiological plausibility.

Conclusion: QTcNet, trained on large-scale algorithmically labelled data, consistently outperformed conventional algorithms across three independent, external validation datasets. Fine-tuning of QTcNet may adapt the model to the characteristics of specific cohorts but reduces external validity in other cohorts. We openly release the full model and code, along with a ready-to-use online implementation at https://qtcnet.uni-muenster.de, facilitating further research and community-driven improvement.