Europace最新文献

Background and aims: The long-term impact of left atrial appendage occlusion (LAAO) plus ablation for atrial fibrillation remains controversial. The present study aims to compare the three-year clinical outcomes of LAAO patients with or without one-staged ablation.

Methods: The RECORD study (NCT03917563) was a prospective registry conducted in 39 participating sites in China between 1st April 2019 and 31st October 2020, which consecutively enrolled 3,082 patients who successfully received the WATCHMAN LAAO device. The current study compared patients who received LAAO only to patients who underwent LAAO plus ablation. A 1:1 propensity score matching was performed to attenuate confounding. The primary outcome was a composite endpoint of cardiovascular death, stroke, and systemic embolism at three-year.

Results: 1,633/2,928 (55.8%) patients received LAAO only and 1,295/2,928 (44.2%) received LAAO plus ablation. After propensity score matching, 1,016/2,032 (50.0%) were in the LAAO group and 1,016/2,032 (50.0%) in the LAAO plus ablation group. The mean±SD age was 68.8±9.3 years, with 815 (40.1%) participants being female. The mean±SD CHA2DS2-VASc and HAS-BLED scores at baseline were 3.9±1.8 and 2.4±1.1, respectively. At three-year, compared to LAAO only, LAAO plus ablation was associated with a lower risk of cardiovascular death, stroke, systemic embolism (6.9%vs.10.4%, HRPSM:0.66, 95%CI:0.49-0.89, p=0.007), which was driven mainly by the lower risk of cardiovascular death (3.7%vs.7.3%, HRPSM:0.50, 95%CI:0.34-0.74, p=0.001). No significant between-group differences were noted for BARC-defined bleeding.

Conclusion: LAAO plus ablation was associated with a lower risk of a composite of cardiovascular death, stroke, and systemic embolism than LAAO only at three-year. However, given the observational nature of the current study, the results should be considered as hypothesis-generating only.

Aims: Though pulsed-field ablation (PFA) has demonstrated an excellent safety profile in reducing collateral injury to the oesophagus and phrenic nerve, it is still associated with specific effects, including electrode heating, haemolysis, and electrolysis due to excessive energy dispersion. This study aims to assess whether saline irrigation during PFA application could mitigate these risks.

Methods and results: To comprehensively evaluate the effect of irrigation with the variable-loop circular catheter (VLCC), the following experiments were performed: (i) ex-vivo potato model: to evaluate the lesion depth, bubble formation, and thermal effects in different irrigation regimens; (ii) in vitro blood pool and cardiac ablation: to determine the haemolysis status and tissue temperature change after PFA; (iii) in vivo swine ablation (n = 8), and (iv) clinical randomized trial (n = 25): to compare the efficacy and safety profile between low (4 mL/min) and high (30 mL/min) flow irrigation using the VLCC. Though peak core temperatures at 5 mm depth were all < 50°C under low- and high-irrigation, high irrigation significantly mitigated the instant electrode and deep tissue heating both in the potato and isolated cardiac models. Ex vivo potato slices showed that high-flow irrigation produced the deepest lesion sets when compared to low-flow irrigation (5.94 ± 0.29 mm vs. 5.36 ± 0.33 mm, P = 0.043). Assessment from a high-speed camera and bubble detector demonstrated that high-flow irrigation significantly reduced the total number of gaseous bubbles (54.50 IQR 53.00-56.75 vs. 82.00 IQR 72.00-83.00, P < 0.001) and eliminated the occurrence of larger bubbles. The high-flow irrigation group showed a smaller increase in the level of free haemoglobin immediately after the procedure across the blood pool, swine, and clinical models. Haptoglobin and lactate dehydrogenase levels were also attenuated by high irrigation in the in vivo swine model and clinical trial. One swine in the low-irrigation group developed an acute cerebral lesion (3 mm). The clinical trial confirmed that the incidence of silent cerebral lesions was significantly lower in the high-flow irrigation group (16.7% vs. 66.7%, P = 0.036).

Conclusion: Proper saline irrigation during PFA with VLCC may mitigate electrode-associated haemolysis, reduce electrode and tissue temperature, limit bubble aggregation, and be associated with a lower incidence of silent cerebral lesions, the clinical significance of which remains unclear.

Aims: Electromechanical coupling and mechano-electrical feedback (MEF) are crucial for cardiac function, but their pro-arrhythmic roles in short and long QT syndromes (SQT1 and LQT2) are not fully understood. We aimed to evaluate MEF-induced electrical changes, their arrhythmic impact, and the involvement of stretch-activated channels (SACs) in transgenic rabbit models of SQT1 and LQT2.

Methods and results: Patch-clamp and fluorescence imaging were used to analyse action potential duration (APD), Ca²⁺ transients, and contractility in ventricular cardiomyocytes (VCMs) from LQT2, SQT1 and wild-type (WT) rabbits. LQT2 cells showed prolonged APD and Ca²⁺ transients, increased early afterdepolarizations, Ca²⁺ oscillations, and impaired mechanics compared to WT and SQT1. The cellular electromechanical window (Ca²⁺-transient duration minus APD) was more negative in LQT2 and more positive in SQT1 than in WT. QTc prolonged with preload/afterload increase and decreased with preload reduction across all genotypes, but MEF-induced QTc changes and dispersion were most pronounced in LQT2. Ex vivo Langendorff experiments showed that increased right ventricular (RV) pressure prolonged APD and QTc in WT hearts. This was attenuated by the SAC blocker GSMTx4, suggesting a role for SACs in MEF. In silico models of human VCMs including SACs confirmed higher vulnerability to stretch/MEF-induced arrhythmias, including re-entry, in SQT1 and LQT2.

Conclusion: Mechano-electrical feedback-induced electrical changes, partly mediated by SACs, occur in WT, SQT1, and LQT2, but MEF effects are strongest in LQT2. Mechano-electrical feedback induces pro-arrhythmic effects in silico more prominently in LQT2 and SQT1 than in WT, highlighting the potential pro-arrhythmic role of MEF in a vulnerable electrophysiological substrate.

Aims: Loss-of-function (LOF) mutations of the cardiac Na+ channel (SCN5A) are causatively associated with the Brugada Syndrome (BrS). However, the onset of Ventricular Fibrillation (VF) is a rare event, and critical factors favouring the pathological phenotype remain often elusive. This study explores how concomitant triggering conditions may impact on VF onset in a symptomatic proband carrying the S805L/SCN5A BrS mutation.

Methods and results: Clinical, in-vitro, numerical, and structural analyses were performed. A 67-year-old male was resuscitated after cardiac arrest, and clinical analysis upon hospitalisation revealed severe hypokalaemia (2.5 mEq/L). The ECG showed a coved type-I BrS pattern and the SCN5A mutation (S805L) was identified. Patch-clamp studies carried out in a heterologous expression system (HEK293 cells) revealed that WT/S805L channels exhibit two different phenotypes (normal and LOF); the main parameter controlling this distribution is the cell membrane potential. A protected/normal behaviour was observed at -80 mV; conversely, LOF occurred at more negative potentials (-100/-120 mV). Further analyses in isolated outflow tract ventricular cardiomyocytes showed that hypokalaemia (and bradycardia) induced diastolic potential hyperpolarisation, thus favouring the Na+ current LOF. Computational and molecular modelling confirmed our findings and revealed the structural determinant of this alteration.

Conclusion: WT/S805L Na+ channels exhibit either a LOF or a wild-type-like behaviour depending on the membrane potential. Since hypokalaemia and slow pacing rate induce cell hyperpolarisation and the associated LOF, they represent concurrent elements creating the scenario responsible for the VF and cardiac arrest. These results may represent an interpretative paradigm applicable to other BrS mutations.

Aims: A dual-chamber leadless pacemaker (LP) system relies on a beat-to-beat, wireless, implant-to-implant (i2i™) communication between implanted devices in the right atrium and right ventricle (A-to-V and V-to-A). Atrioventricular (AV) synchrony was evaluated during an ambulatory 24 h period of daily living to determine if its effectiveness can be maintained under real-world conditions.

Methods and results: A prospective, single-arm, multicentre clinical study (ClinicalTrials.gov identifier NCT05252702) evaluated the overall safety and performance of the dual-chamber LPs in patients with standard indications for dual-chamber pacing. Following the 3-month visit, eligible patients wore 12-lead Holter monitors for 24 h while resuming the activities of daily living while under clinically driven programmed settings. Leadless pacemaker diagnostic data were interrogated when patients returned to the clinic. An independent Holter core laboratory adjudicated the proportion of synchronous beats (PR intervals within paced and sensed AV delay bounds). Relationships between AV synchrony and i2i communication success rate, implant indication, heart rate, and AV event type were evaluated. Among 47 analysable patients, mean AV synchrony was achieved in 96.7% of beats, exceeding mean A-to-V and V-to-A transmission success rates of 93.4% and 92.1%, respectively. There were no significant differences in AV synchrony between sinus node and AV block patients. Across all AV paced/sensed cycle combinations and heart rate ranges (including >100 b.p.m.), AV synchrony was sustained >90% in an ambulatory real-world setting.

Conclusion: A dual-chamber leadless pacing system demonstrated >96% overall AV synchrony for a 24 h period of daily living while programmed to clinically appropriate settings, thus showing that true dual-chamber DDD(R) pacing can be maintained in a real-world environment.

Aims: The rising popularity of endurance races underscores the need to explore the risks of sports-related sudden cardiac arrest (Sr-SCA). Although rare, Sr-SCA is significantly more prevalent in men than in women. The mechanisms underlying these sex differences remain unclear.We aimed to investigate the incidence rates, clinical characteristics, aetiologies, sex differences, and exercise performances among SCA cases during major endurance races in Paris over a 10-year period.

Methods and results: We Analysed the Paris Sudden Death Expertise Centre Registry Data (Covering 2011-2024, excluding 2020). This included SCA cases from the half marathon, full marathon and 20 km Parisian race events. We calculated the incidence rates for men and women, with performance analyses focusing on acceleration patterns and the relative risk of SCA in the final kilometre. Among the 1.2 million participants, 17 SCA cases (88% male) were identified, yielding crude incidences of 16.9 and 5.7 per million for men and women, respectively. Sr-SCA was overrepresented in the final kilometres of short races. Men exhibited twice the acceleration rate that women did. Despite extensive medical investigations, no cause was identified in 47.1% of the cases, underscoring the idiopathic nature of Sr-SCA. After hospitalization, 88% (15/17) of the cases survived, all with excellent neurological outcomes [cerebral performance category (CPC) 1], except for one CPC 2.

Conclusion: SCA incidences during endurance races are low, with male predominance, high survival rates, and a high proportion of unexplained cases. The male-specific acceleration in the final kilometre may suggest that physiological and behavioural factors influence SCA risk.

Ventricular tachycardia (VT) and ventricular fibrillation remain major contributors to sudden cardiac death, with current therapies limited by our incomplete understanding of the arrhythmogenic substrate. This narrative review explores recent developments in computer-aided techniques for characterizing the arrhythmogenic substrate, focusing on post-myocardial infarction VT. High-resolution cardiac imaging now enables detailed visualization of structural abnormalities, including heterogeneous scar architecture and fatty infiltration. Sophisticated invasive mapping techniques provide insights into local electrophysiological properties, while novel non-invasive mapping approaches offer complementary views of global electrical patterns. Integration of these modalities through computational simulations allows for mechanistic insights into arrhythmia initiation and maintenance, particularly in post-myocardial infarction VT, where structural and functional substrates interact in complex ways. Emerging artificial intelligence applications enhance substrate analysis through automated feature extraction and pattern recognition, enabling more sophisticated risk stratification. These computer-aided approaches are advancing from research tools to clinical applications, with early evidence suggesting improved ablation outcomes and better risk prediction. However, significant challenges remain in validation, standardization, and clinical implementation of these innovations. This narrative review highlights recent methodological advances and clinical applications of computer-aided substrate characterization, and conceptualizes future directions towards personalized arrhythmia management, also beyond post-infarction VTs.

Aims: Concomitant pulsed field ablation (PFA) for atrial fibrillation (AF) with left atrial appendage closure (LAAC) offers a single-procedure approach for arrhythmia control and thromboembolic risk reduction. This study assessed the workflow, safety, and feasibility of combined PFA and LAAC in routine practice.

Methods and results: We prospectively analysed patients undergoing zero-fluoroscopy PFA, with low fluoroscopy for LAAC. Pre-procedural planning used CT imaging and AI-based models for device selection and landing-zone assessment. A single transseptal puncture facilitated intracardiac echocardiography, PFA catheter, and LAAC sheath. A total of 209 patients were included (56% male; mean age 76.5 ± 7.8 years), with 59.3% paroxysmal AF, 40.7% persistent AF, and 50% de novo AF. The mean CHA2DS2-VASc score was 4.5. Mean procedure and left atrial dwell times were 57.3 ± 17 and 45.1 ± 13.6 min, respectively; fluoroscopy averaged 3.4 ± 0.8 min for LAAC. A single LAAC device was used in 94% of cases, achieving adequate seal in all. No pericardial effusion, phrenic nerve injury, kidney, or oesophageal injury occurred; two patients had minor groin bleeding. All were discharged same day on oral anticoagulation for 90 days. Follow-up CT (80%) or TEE (20%) at 111.6 ± 16.5 days showed no leaks >2 mm, a 4.7% small-leak rate, and two device-related thrombi without stroke, managed with extended anticoagulation.

Conclusion: Combined PFA and LAAC is feasible and safe with favourable early outcomes. Multi-centre studies are warranted to confirm findings and standardize this workflow for broader clinical adoption.