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This State of the Future Review describes and discusses the potential transformative power of digital twins in cardiac electrophysiology. In this 'big picture' approach, we explore the evolution of mechanistic modelling based digital twins, their current and immediate clinical applications, and envision a future where continuous updates, advanced calibration, and seamless data integration redefine clinical practice of cardiac electrophysiology. Our aim is to inspire researchers and clinicians to embrace the extraordinary possibilities that digital twins offer in the pursuit of precision medicine.

Athletes are predisposed to atrial arrhythmias but the association between intense endurance exercise training, ventricular arrhythmias (VAs), and sudden cardiac death is less well established. Thus, it is unclear whether the 'athlete's heart' promotes specific arrhythmias or whether it represents a more general pro-arrhythmogenic phenotype. Whilst direct causality has not been established, it appears possible that repeated exposure to high-intensity endurance exercise in some athletes contributes to formation of pro-arrhythmic cardiac phenotypes that underlie VAs. Theories regarding potential mechanisms for exercise-induced VAs include repeated bouts of myocardial inflammation and stretch-induced cellular remodelling. Small animal models provide some insights, but larger animal and human data are sparse. The current clinical approach to VAs in athletes is to differentiate those with and without structural or electrical heart disease. However, if the athlete's heart involves a degree of pro-arrhythmogenic remodelling, then this may not be such a simple dichotomy. Questions are posed by athletes with VAs in combination with extreme remodelling. Some markers, such as scar on magnetic resonance imaging, may point towards a less benign phenotype but are also quite common in ostensibly healthy athletes. Other clinical and invasive electrophysiology features may be helpful in identifying the at-risk athlete. This review seeks to discuss the association between athletic training and VAs. We will discuss the potential mechanisms, clinical significance, and approach to the management of athletes with VAs.

Aims: Pulsed field ablation (PFA) is an innovative technology recently adopted for the treatment of atrial fibrillation (AF). Preclinical and clinical studies have reported a remarkable safety profile, as a result of its tissue-specific effect targeting cardiomyocytes and sparing adjacent tissues. Single-shot pentaspline system was the first PFA device to receive regulatory approval. We performed a meta-analysis to compare the efficacy and safety of PFA with the single-shot pentaspline system vs. currently available second-/third-/fourth-generation cryoballoon ablation (CRYO) technologies.

Methods and results: We systematically searched electronic databases for studies focusing on AF ablation employing the PFA single-shot pentaspline system or second-/third-/fourth-generation CRYO technologies. The primary endpoints were acute procedural success assessed on a vein and patient basis. Safety endpoints included overall periprocedural complications and major periprocedural complications. We also compared procedural, fluoroscopy times, and freedom from atrial tachyarrhythmias (ATs) at follow-up (secondary endpoints). Twenty and 70 studies were included for PFA and CRYO, respectively. Pulsed field ablation demonstrated greater acute procedural success on a vein basis (99.9% vs. 99.1%; P < 0.001), as well as per patient (99.5% vs. 98.4%; P < 0.001). Pulsed field ablation yielded lower overall periprocedural complications (3.1% vs. 5.6%; P < 0.001), shorter procedural time (75.9 min vs. 105.6 min; P < 0.001), and fluoroscopy time (14.2 min vs. 18.9 min; P < 0.001) compared with CRYO. No differences were found for major periprocedural complications (1.2% vs. 1.0%; P = 0.46) and freedom from ATs at 1 year (82.3% vs. 80.3%; log-rank P = 0.61).

Conclusion: Pulsed field ablation contributed to higher acute procedural success and safety compared with CRYO. No statistically significant differences in AT recurrence at 1-year follow-up were observed.

Aims: Little is known about the distribution and clinical course of patients with inherited arrhythmia syndrome (IAS) and concomitant atrial arrhythmias (AAs). The aim of the study is (i) to characterize the distribution of AAs in patients with IAS and (ii) evaluate the long-term clinical course of these patients.

Methods and results: An international multicentre study was performed and involved 28 centres in 16 countries. Inclusion criteria were (i) IAS and (ii) electrocardiographic documentation of AAs. The primary endpoint was a composite of sudden cardiac death, sustained ventricular arrhythmias (VAs), or appropriate implantable cardioverter defibrillator (ICD) interventions. Strokes, inappropriate ICD shocks due to AAs, and the occurrence of sinus node dysfunction were assessed. A total of 522 patients with IAS and AAs were included. Most patients were diagnosed with Brugada syndrome (n = 355, 68%) and long QT syndrome (n = 93, 18%). The remaining patients (n = 71, 14%) presented with short QT syndrome, early repolarization syndrome, catecholaminergic polymorphic ventricular tachycardia, progressive cardiac conduction diseases, or idiopathic ventricular fibrillation. Atrial fibrillation was the most prevalent AA (82%), followed by atrial flutter (9%) and atrial tachycardia (9%). Atrial arrhythmia was the first clinical manifestation of IAS in 52% of patients. More than one type of AA was documented in 23% of patients. Nine patients (3%) experienced VA before the diagnosis of IAS due the use of anti-arrhythmic medications taken for the AA. The incidence of the primary endpoint was 1.4% per year, with a two-fold increase in patients who experienced their first AA before the age of 20 (odds ratio 2.2, P = 0.043). This was consistent across the different forms of IAS. Inappropriate ICD shock due to AAs was reported in 2.8% of patients, strokes in 4.4%, and sinus node dysfunction in 9.6%.

Conclusion: Among patients with IAS and AAs, AA is the first clinical manifestation in about half of the cases, with more than one form of AAs present in one-fourth of the patients. The occurrence of AA earlier in life may be associated with a higher risk of VAs. The occurrence of stroke and sinus node dysfunction is not infrequently in this cohort.

Aims: Whether adjusting the duration of ablation based on left atrial wall thickness (LAWT) provides extra benefits for pulmonary vein (PV) isolation for atrial fibrillation (AF) is uncertain. We studied the safety and efficacy of tailored cryoballoon PV isolation (CB-PVI) based on LAWT for paroxysmal AF.

Methods and results: Two hundred seventy-seven patients with paroxysmal AF refractory to anti-arrhythmic drug were randomized 1:1 to either LAWT-guided CB-PVI (n = 135) and empirical CB-PVI (n = 142). Empirical CB-PVI was performed using a 28 mm cryoballoon with recommended application for 240 s per ablation. Cryoapplication in the LAWT-guided group was titrated (additional application for 120 s at PVs, where >25% of the circumference includes segments with LAWT > 2.5 mm and reduced baseline application to 180 s at PVs where >75% of the circumference includes segments with LAWT < 1.5 mm) according to the computed tomography LAWT colour map. The primary endpoint was freedom from any documented atrial arrhythmia of more than 30 s without antiarrhythmic medication, after a single ablation procedure. During a mean follow-up of 18.7 months, patients in the LAWT-guided CB-PVI group (70.8%) had a higher event-free rate from primary endpoint than those in the empirical CB-PVI group (54.4%; hazard ratio 0.64, 95% confidence interval 0.42-0.99; P = 0.043). No differences were observed between the groups in complication rates (3.0% in LAWT-guided vs. 4.9% in empirical CB-PVI). The total procedure time was extended in the LAWT group than in the empirical group (mean 70.2 vs. 65.2 min, respectively).

Conclusion: The LAWT-guided energy titration strategy improved freedom from atrial arrhythmia recurrence, compared with conventional strategy.

Atrial fibrillation (AF) remains the most common cardiac arrhythmia worldwide and is associated with significant morbidity and mortality. The European Society of Cardiology (ESC)/European Association for Cardio-Thoracic Surgery (EACTS) have recently released the 2024 guidelines for the management of AF. This review highlights 10 novel aspects of the ESC/EACTS 2024 Guidelines. The AF-CARE framework is introduced, a structural approach that aims to improve patient care and outcomes, comprising of four pillars: [C] Comorbidity and risk factor management, [A] Avoid stroke and thromboembolism, [R] Reduce symptoms by rate and rhythm control, and [E] Evaluation and dynamic reassessment. Additionally, graphical patient pathways are provided to enhance clinical application. A significant shift is the new emphasis on comorbidity and risk factor control to reduce AF recurrence and progression. Individualized assessment of risk is suggested to guide the initiation of oral anticoagulation to prevent thromboembolism. New guidance is provided for anticoagulation in patients with trigger-induced and device-detected sub-clinical AF, ischaemic stroke despite anticoagulation, and the indications for percutaneous/surgical left atrial appendage exclusion. AF ablation is a first-line rhythm control option for suitable patients with paroxysmal AF, and in specific patients, rhythm control can improve prognosis. The AF duration threshold for early cardioversion was reduced from 48 to 24 h, and a wait-and-see approach for spontaneous conversion is advised to promote patient safety. Lastly, strong emphasis is given to optimize the implementation of AF guidelines in daily practice using a patient-centred, multidisciplinary and shared-care approach, with the simultaneous launch of a patient version of the guideline.

Aims: We aimed to investigate the risk of sinus node dysfunction (SND) indicating cardiac pacing and mortality in first-degree relatives to patients with a pacemaker implanted on this indication and assess the effect of onset-age on disease risk.

Methods and results: In this nationwide register-based study, we used the Danish Civil Registration Registry to establish family structures and merged data with the Danish National Patient Registry and the Danish Pacemaker and ICD Registry containing information on all pacemakers implanted due to SND in Denmark. We followed 6 027 090 individuals born after 1954 in the period between 1982 and 2022 (180 775 041 person-years) among whom 2.477 pacemakers were implanted due to SND. The adjusted rate ratio (RR) of pacemaker-treated SND was 2.9 (2.4-3.6) for individuals having any father, mother, or sibling with a pacemaker implanted on this indication compared with the general population (derived cumulative incidence at the age of 68 years: 0.79 and 0.27%, respectively). This risk was inversely proportional to implantation age in the index person [≤60 years: RR = 5.5 (3.4-9.0)]. Overall, mortality was similar between individuals having a father, mother, or sibling with SND and the general population, but higher for relatives to index persons with an early onset [≤60 years: RR = 1.22 (1.05-1.41)].

Conclusion: First-degree relatives to SND patients are at increased risk of SND with risk being inversely associated with pacemaker implantation age in the index person. Mortality in first-degree relatives was comparable with the general population, although subgroup findings suggest an increased mortality among individuals with a family history of early-onset SND.

Background: Temperature-controlled high-power short-duration (HPSD) radiofrequency catheter ablation for pulmonary vein isolation (PVI) utilizing a novel ablation catheter (QDOT Micro) with real-time assessment of catheter tip temperature aims for safer, more effective and faster procedures.

Methods: The peQasus study is a large European multicenter study set up to assess safety, acute efficacy and outcomes of temperature-controlled HPSD based PVI. The primary endpoints were safety, efficacy and 12-months freedom from atrial tachyarrhythmias. Additionally, two strategies namely very HPSD (90W for 4 seconds) only and a hybrid approach (HPSD with maximum of 50W and vHPSD) were compared.

Results: A total of 1,023 AF patients in 15 centers from 9 European countries received PVI with the QDOT. Complete PVI was successfully achieved in all patients. In 699/1023 (68.3%) the vHPSD only approach (vHPSD group) and in 324/(31.7%) patients the hybrid approach (hybrid group) was utilized. The mean procedure duration was 98.4±37.4 min (vHPSD: 88.2±34.9min, hybrid: 117.4±32.7min, p<0.001). The first pass isolation rate of all PVs was 64% (vHPSD: 62.6%, hybrid: 67.1%, p=0.187). Severe adverse events were observed in 1.7% (vHPSD: 1.6%, hybrid: 1.9%, p=0.746). 12-month arrhythmia-recurrence free survival was 77.1% (vHPSD: 76.8%, hybrid: 77.8%, p=0.241).

Conclusions: In this large multicentre study temperature-controlled HPSD and vHPSD ablation via a novel ablation catheter provides safe and effective PVI with a relatively short procedure duration. Despite a shorter procedure time no differences in terms of safety and freedom from arrhythmia-recurrence were found irrespective of utilizing vHPSD or the hybrid approach.