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In 1924, the Dutch physiologist Willem Einthoven received the Nobel Prize in Physiology or Medicine for his discovery of the mechanism of the electrocardiogram (ECG). Anno 2024, the ECG is commonly used as a diagnostic tool in cardiology. In the paper 'Le Télécardiogramme', Einthoven described the first recording of the now most common cardiac arrhythmia: atrial fibrillation (AF). The treatment of AF includes rhythm control, aiming to alleviate symptoms and improve quality of life. Recent studies found that early rhythm control might additionally improve clinical outcomes. However, current therapeutic options have suboptimal efficacy and safety, highlighting a need for better rhythm-control strategies. In this review, we address the challenges related to antiarrhythmic drugs (AADs) and catheter ablation for rhythm control of AF, including significant recurrence rates and adverse side effects such as pro-arrhythmia. Furthermore, we discuss potential solutions to these challenges including novel tools, such as atrial-specific AADs and digital-twin-guided AF ablation. In particular, digital twins are a promising method to integrate a wide range of clinical data to address the heterogeneity in AF mechanisms. This may enable a more mechanism-based tailored approach that may overcome the limitations of previous precision medicine approaches based on individual biomarkers. However, several translational challenges need to be addressed before digital twins can be routinely applied in clinical practice, which we discuss at the end of this narrative review. Ultimately, the significant advances in the detection, understanding, and treatment of AF since its first ECG documentation are expected to help reduce the burden of this troublesome condition.

In 2024, we celebrate the 100th anniversary of Willem Einthoven receiving the Nobel Prize for his discovery of the mechanism of the electrocardiogram (ECG). Building on Einthoven's legacy, electrocardiography allows the monitoring of cardiac bioelectricity through solutions to the so-called forward and inverse problems. These solutions link local cardiac electrical signals with the morphology of the ECG, offering a reversible connection between the heart's electrical activity and its representation on the body surface. Inspired by Einthoven's work, researchers have explored the transition from monitoring to modulation of bioelectrical activity in the heart for the development of new anti-arrhythmic strategies, e.g. via optogenetics. In this review, we demonstrate the lasting influence that Einthoven has on our understanding of cardiac electrophysiology in general, and the diagnosis and treatment of cardiac arrhythmias in particular.

Aims: Trials on integrated care for atrial fibrillation (AF) showed mixed results in different AF populations using various approaches. The multicentre, randomized AF-EduCare trial evaluated the effect of targeted patient education on unplanned cardiovascular outcomes.

Methods and results: Patients willing to participate were randomly assigned to in-person education, online education, or standard care (SC) and followed for minimum 18 months. Education focused on four aspects of integrated AF care: (i) knowledge on AF and oral anticoagulation; (ii) reinforcement of medication adherence; (iii) awareness about risk factors; and (iv) reachability for AF-related questions. The primary endpoint was the composite of cumulative events of unplanned cardiovascular hospitalizations and consultations, emergency department visits for cardiovascular reasons, and cardiovascular death. A total of 1038 patients (69.8 ± 9.2 years) were followed up for 26.9 ± 9.4 months. Education (both in-person and online) significantly improved AF-related knowledge compared to SC (P < 0.001), increased patient awareness about risk factors, led to high medication adherence, and encouraged patients to ask health-related questions. However, in-person education did not show an effect on the primary outcome compared to SC [HR 1.02 (0.91-1.14); P = 0.80] that was also not the case when comparing online education vs. SC [HR 1.18 (0.95-1.46), P = 0.65]. Exploratory subgroup analyses showed a heterogeneous effect over the centres, but a positive impact of in-person education in patients with asymptomatic AF, being 70 years old or younger, and without a history of heart failure.

Conclusion: AF-EduCare showed that intensive targeted patient education did not lead to less unplanned cardiovascular events in the AF patient population as a whole, although subgroups might benefit.

Aims: In repaired tetralogy of Fallot (rTOF), the septal anatomical isthmuses (AI), AI 3, between the ventricular septal defect (VSD) and pulmonary annulus, and AI 4, between the VSD and tricuspid annulus, are important ventricular tachycardia (VT) substrates when slow conducting. Our aim was to assess the influence of VSD characteristics, specifically the presence of muscular or fibrous tissue at its border, on the presence or absence of septal AIs, potentially related to VT.

Methods and results: All consecutive rTOF patients who underwent electroanatomical mapping between January 2005 and March 2023 with an available surgical report providing VSD details (n = 91) were included. The majority of patients had an outlet perimembranous VSD (n = 76, 84%), 6 (7%) an outlet muscular VSD, and 7 (8%) a doubly committed juxta-arterial VSD. In patients with an outlet perimembranous VSD, AI 3 was present in almost all (97%), whereas no AI 4 was observed. In patients with an outlet muscular VSD, AI 3 and AI 4 were present in 83% and 33%, respectively. In all patients with a doubly committed VSD, where the outlet septum is hypoplastic/fibrous, AI 3 was absent. Among patients with a doubly committed VSD with a muscular postero-inferior rim, 50% had AI 4, whereas none of those with a fibrous postero-inferior rim had AI 4.

Conclusion: Ventricular septal defect characteristics aid in determining the presence of septal AIs potentially related to VT. In patients with doubly committed VSDs, septal VT substrates are unlikely. Detailed knowledge of anatomical VSD characteristics is desirable for understanding VT in rTOF.

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.