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Background: Little is known about the distribution and clinical course of patients with inherited arrhythmia syndrome (IAS) and concomitant atrial arrhythmias (AAs)., Aim: 1) to characterize the distribution of AAs in patients with IAS and 2) evaluate the long-term clinical course of these patients., Methods: An international multicenter study was performed and involved 28 centers in 16 countries. Inclusion criteria were: 1) IAS and 2) ECG documentation of AAs. The primary endpoint was a composite of sudden cardiac death, sustained VAs or appropriate ICD interventions. Strokes, inappropriate ICD shocks due to AAs, and the occurrence of sinus node dysfunction were assessed., Results: 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 (ERS), catecholaminergic polymorphic ventricular tachycardia (CPVT), progressive cardiac conduction diseases, or idiopathic ventricular fibrillation. Atrial fibrillation (AF) was the most prevalent AA (82%), followed by atrial flutter (9%) and atrial tachycardia (9%). AA was the first clinical manifestation of IAS in 52% of patients. More than one type of AAs 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 twofold increase observed in patients who experienced their first AA before the age of 20 (OR 2.2, p=0.043). This was consistent across the different forms of IAS. Inappropriate ICD shock due to AAs were reported in 2.8% of patients, strokes in 4.4% and sinus node dysfunction in 9.6%., Conclusions: 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 ventricular arrhythmias. The occurrence of stroke and sinus node dysfunction is not-infrequently in this cohort., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

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 toward 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., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Brugada syndrome (BrS) is an inherited cardiac condition that increases the risk of sudden cardiac death (SCD) due to ventricular arrhythmias. Catheter ablation has been shown to effectively reduce recurrent ventricular fibrillation (VF) episodes through targeting of abnormal electrograms predominantly located within the anterior surface of the right ventricular outflow tract. Signal frequency mapping is an emerging concept that provides further definition of pathological ventricular substrate., Case Summary: A 66-year-old male with BrS was admitted to our institution with implantable cardioverter defibrillator shocks for VF. Electro-anatomical mapping (EAM) and ablation were performed utilizing a novel automated frequency-based strategy. Combined automated frequency and low voltage maps were generated to define high frequency, low voltage (HF-LVo) depolarization abnormalities within the QRS complex. Low frequency, low voltage (LF-LVo) regions from the QRS terminal notch to the T-wave offset were also identified. The combined HF-LVo and LF-LVo map areas totalled 12.4 cm 2 , compared to the conventional low voltage and late potential map areas, which were 44 cm 2 and 27.8 cm 2 , respectively. The ablation strategy targeted HF-LVo and LF-LVo regions only. Following ablation, re-mapping demonstrated near complete abolition of HF-LVo and LF-LVo regions, with no inducible ventricular arrhythmias during extra-stimulation testing. During follow-up, ECG normalization was observed, with no further ventricular arrhythmias and a negative ajmaline challenge at 6 months., Discussion: Catheter ablation for BrS utilizing a novel automated combined frequency and low voltage EAM approach can objectively identify relevant substrate. The results demonstrate adequate substrate modification with comparable ablation target areas to previous studies and encouraging clinical outcomes., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Patients presenting with or alerting emergency networks due to acute heart failure (AHF) form a diverse group with a plethora of symptoms, risks, comorbidities, and aetiologies. During AHF, there is an increased risk of destabilizing the functional substrate and modulatory adding to the risk of ventricular arrhythmias (VAs) already created by the structural substrate. New VAs during AHF have previously identified patients with higher intra-hospital and 60-day morbidity and mortality. Risk stratification and criteria/best time point for coronary intervention and implantable cardioverter defibrillator implantation, however, are still controversial topics in this difficult clinical setting. The characteristics and logistics of pre-hospital emergency medicine, as well as the density of centres capable of treating AHF and VAs, differ massively throughout Europe. Scientific guidelines provide clear recommendations for the management of arrhythmias in patients with chronic heart failure. However, the incidence, significance, and management of arrhythmias in patients with AHF have been less studied. This consensus paper aimed to address the identification and treatment of VAs that complicate the course of patients who have AHF, including cardiogenic shock., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: Patients undergoing catheter ablation (CA) of ventricular arrhythmias (VAs) are generally observed overnight in the hospital given the concern for complications. To evaluate the efficacy and safety of same-day discharge (SDD) of patients undergoing elective CA of premature ventricular complexes (PVCs)., Methods and Results: A retrospective evaluation of all patients undergoing elective VA ablation at Ascension St Vincent Hospital from 1 January 2018 to 31 December 2019 was undertaken. Of those, the patients undergoing PVC ablation were divided into SDD and non-SDD. Patients underwent SDD at the discretion of the operator. The primary safety outcome was the 30-day incidence of complications and death. The primary efficacy outcome was procedural success. Among 188 patients who underwent VA ablation, 98 (52.1%) were PVC ablations, and of those, 55 (56.1%) were SDD. There was no difference in age, gender, comorbidities, or ejection fraction between the two groups. Patients that were non-SDD were more likely to be on chronic anticoagulation (P = 0.03), have ablation in the LV (P = 0.04), have retrograde access (P = 0.03), and receive heparin during the procedure (P = 0.01). There were no complications in the SDD group compared with one (2.3%) in the non-SDD group. There was no difference in primary efficacy between the two groups with a 90.9% acute success in the SDD and 88.4% in the non-SDD (P = 0.68)., Conclusion: Same-day discharge for CA of PVCs is feasible and could lower healthcare resource utilization without compromising outcomes in this unique population., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background and Aims: Risk scores are proposed for genetic arrhythmias. Having proposed in 2010 one such score (M-FACT) for the long QT syndrome (LQTS), this study aims to test whether adherence to its suggestions would be appropriate., Methods: LQT1/2/3 and genotype-negative patients without aborted cardiac arrest (ACA) before diagnosis or cardiac events (CEs) below age 1 were included in the study, focusing on an M-FACT score ≥2 (intermediate/high risk), either at presentation (static) or during follow-up (dynamic), previously associated with 40% risk of implantable cardioverter defibrillator (ICD) shocks within 4 years., Results: Overall, 946 patients (26 ± 19 years at diagnosis, 51% female) were included. Beta-blocker (βB) therapy in 94% of them reduced the rate of those with a QTc ≥500 ms from 18% to 12% (P < .001). During 7 ± 6 years of follow-up, none died; 4% had CEs, including 0.4% with ACA. A static M-FACT ≥2 was present in 110 patients, of whom 106 received βBs. In 49/106 patients with persistent dynamic M-FACT ≥2, further therapeutic optimization (left cardiac sympathetic denervation in 55%, mexiletine in 31%, and ICD at 27%) resulted in just 7 (14%) patients with CEs (no ACA), with no CEs in the remaining 57. Additionally, 32 patients developed a dynamic M-FACT ≥2 but, after therapeutic optimization, only 3 (9%) had CEs. According to an M-FACT score ≥2, a total of 142 patients should have received an ICD, but only 22/142 (15%) were implanted, with shocks reported in 3., Conclusions: Beta-blockers often shorten QTc, thus changing risk scores and ICD indications for primary prevention. Yearly risk reassessment with therapy optimization leads to fewer ICD implants (3%) without increasing life-threatening events., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Competing Interests: Conflict of interests: None declared.

Background: Some patients affected by mitral valve (MV) prolapse (MVP) are at higher risk of ventricular arrhythmias (VAs), but the underlying pathogenesis, as well as the effects of surgery on VA, remain not fully understood. Mitral valve repair, however, represents a privileged point of view to deepen the understanding of arrhythmogenesis in this context. Hence, we report an interesting case of MV re-repair., Case Summary: A 52-year-old man was referred to our institution for severe mitral regurgitation (MR) due to P2 prolapse in the context of myxomatous MV degeneration. Pre-operative imaging showed systolic mitral annular disjunction, left ventricular (LV) wall curling, Pickelhaube's sign, and a prolapsing tricuspid valve (TV) with only mild regurgitation. Twenty-four-hour electrocardiogram (ECG) Holter revealed a significant burden of premature ventricular contractions (PVCs), most of them originating from anterior papillary muscle (APM), posterior papillary muscle (PPM), and mitral annulus (MA). Quadrangular resection of P2 and mitral annuloplasty were performed. One year later, relapse of severe MR due to a residual P2M1 prolapse occurred. Twenty-four-hour ECG Holter showed no PVCs from PPM and MA, while those from APM persisted. A central edge-to-edge repair was effectively used to fix the residual prolapse. After 1 year from REDO surgery, a third ECG Holter confirmed the absence of any remaining LV PVCs, but still few ectopic beats originating from TV were recorded., Discussion: Here, we report a case of VA resolution after specific, anatomical triggers addressing surgical gestures. Our experience confirms that MV surgery may have a role in MVP patients' arrhythmias correction., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: Previously, we demonstrated that inferolateral mitral annular disjunction (MAD) is more prevalent in patients with idiopathic ventricular fibrillation (IVF) than in healthy controls. In the present study, we advanced the insights into the prevalence and ventricular arrhythmogenicity by inferolateral MAD in an even larger IVF cohort., Methods and Results: This retrospective multi-centre study included 185 IVF patients [median age 39 (27, 52) years, 40% female]. Cardiac magnetic resonance images were analyzed for mitral valve and annular abnormalities and late gadolinium enhancement. Clinical characteristics were compared between patients with and without MAD. MAD in any of the 4 locations was present in 112 (61%) IVF patients and inferolateral MAD was identified in 24 (13%) IVF patients. Mitral valve prolapse (MVP) was found in 13 (7%) IVF patients. MVP was more prevalent in patients with inferolateral MAD compared with patients without inferolateral MAD (42 vs. 2%, P < 0.001). Pro-arrhythmic characteristics in terms of a high burden of premature ventricular complexes (PVCs) and non-sustained ventricular tachycardia (VT) were more prevalent in patients with inferolateral MAD compared to patients without inferolateral MAD (67 vs. 23%, P < 0.001 and 63 vs. 41%, P = 0.046, respectively). Appropriate implantable cardioverter defibrillator therapy during follow-up was comparable for IVF patients with or without inferolateral MAD (13 vs. 18%, P = 0.579)., Conclusion: A high prevalence of inferolateral MAD and MVP is a consistent finding in this large IVF cohort. The presence of inferolateral MAD is associated with a higher PVC burden and non-sustained VTs. Further research is needed to explain this potential interplay., Competing Interests: Conflict of interest: A.H. received a research grant and consultancy fees from GE Healthcare and speaker fees from GE Healthcare and Bayer. He is also a member of the medical advisory board of Medis Medical Imaging Systems and was MRI corelab supervisor of Cardialysis BV until 2022. E.R.B. has consulted for Boston Scientific. S.C.Y. is a consultant for Boston Scientific and has received lecture fees and research grants from Medtronic, Biotronik, and Boston Scientific. The other authors have no conflicts of interest to disclose, (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

The identification of ventricular premature complexes during a cardiological evaluation necessitates the implementation of diagnostic processes aimed at discerning the clinical context that may predispose individuals to a high risk of sudden cardiac death. Epidemiological studies reveal that ventricular premature beats occur in approximately 75% of healthy (or seemingly healthy) individuals, as long as there is no evidence of underlying structural heart disease, such as benign idiopathic ventricular extrasystole originating from the right and left ventricular outflow tracts. In the real world, however, ventricular ectopic beats with morphologies very similar to seemingly benign occurrences are not uncommon. They are notable in subjects exhibiting rapid and complex repetitive forms during exercise testing and Holter electrocardiogram. Additionally, these subjects may display more or less extensive scarring signs on cardiac magnetic resonance and may have a family history of cardiomyopathy and/or sudden cardiac death. Therefore, the purpose of this review is to critically analyse the process of evaluating premature ventricular complexes, which is crucial for accurate risk stratification. The latter cannot overlook some inevitable elements, including morphology, origin, complexity, and the associated clinical setting (absence or presence of structural heart disease)., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background and Aims: Available data on continuous rhythm monitoring by implantable loop recorders (ILRs) in patients with Brugada syndrome (BrS) are scarce. The aim of this multi-centre study was to evaluate the diagnostic yield and clinical implication of a continuous rhythm monitoring strategy by ILRs in a large cohort of BrS patients and to assess the precise arrhythmic cause of syncopal episodes., Methods: A total of 370 patients with BrS and ILRs (mean age 43.5 ± 15.9, 33.8% female, 74.1% symptomatic) from 18 international centers were included. Patients were followed with continuous rhythm monitoring for a median follow-up of 3 years., Results: During follow-up, an arrhythmic event was recorded in 30.7% of symptomatic patients [18.6% atrial arrhythmias (AAs), 10.2% bradyarrhythmias (BAs), and 7.3% ventricular arrhythmias (VAs)]. In patients with recurrent syncope, the aetiology was arrhythmic in 22.4% (59.3% BAs, 25.0% VAs, and 15.6% AAs). The ILR led to drug therapy initiation in 11.4%, ablation procedure in 10.9%, implantation of a pacemaker in 2.5%, and a cardioverter-defibrillator in 8%. At multivariate analysis, the presence of symptoms [hazard ratio (HR) 2.5, P = .001] and age >50 years (HR 1.7, P = .016) were independent predictors of arrhythmic events, while inducibility of ventricular fibrillation at the electrophysiological study (HR 9.0, P < .001) was a predictor of VAs., Conclusions: ILR detects arrhythmic events in nearly 30% of symptomatic BrS patients, leading to appropriate therapy in 70% of them. The most commonly detected arrhythmias are AAs and BAs, while VAs are detected only in 7% of cases. Symptom status can be used to guide ILR implantation., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: Right bundle branch block (RBBB) morphology non-sustained ventricular arrhythmias (VAs) have been associated with the presence of non-ischaemic left ventricular scar (NLVS) in athletes. The aim of this cross-sectional study was to identify clinical and electrocardiogram (ECG) predictors of the presence of NLVS in athletes with RBBB VAs., Methods and Results: Sixty-four athletes [median age 39 (24-53) years, 79% males] with non-sustained RBBB VAs underwent cardiac magnetic resonance (CMR) with late gadolinium enhancement in order to exclude the presence of a concealed structural heart disease. Thirty-six athletes (56%) showed NLVS at CMR and were assigned to the NLVS positive group, whereas 28 athletes (44%) to the NLVS negative group. Family history of cardiomyopathy and seven different ECG variables were statistically more prevalent in the NLVS positive group. At univariate analysis, seven ECG variables (low QRS voltages in limb leads, negative T waves in inferior leads, negative T waves in limb leads I-aVL, negative T waves in precordial leads V4-V6, presence of left posterior fascicular block, presence of pathologic Q waves, and poor R-wave progression in right precordial leads) proved to be statistically associated with the finding of NLVS; these were grouped together in a score. A score ≥2 was proved to be the optimal cut-off point, identifying NLVS athletes in 92% of cases and showing the best accuracy (86% sensitivity and 100% specificity, respectively). However, a cut-off ≥1 correctly identified all patients with NLVS (absence of false negatives)., Conclusion: In athletes with RBBB morphology non-sustained VAs, specific ECG abnormalities at 12-lead ECG can help in detecting subjects with NLVS at CMR., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aims: The electrocardiographic and electrophysiological characteristics of ventricular arrhythmia (VA) arising from the intramural basal inferior septum (BIS) have not been specifically addressed to date. The aim of the current study was to characterize intramural BIS-VA and distinguish it from those with endocardial origins besides clarifying the anatomical configurations of the pyramidal space., Methods and Results: Fifty-five consecutive patients undergoing catheter ablation of VAs from BIS were identified and divided into three groups: the left ventricular (LV)-BIS group (n = 28), right ventricular (RV)-BIS group (n = 8), and intramural group (Intra, n = 19). Compared with the LV-BIS and RV-BIS groups, patients in the Intra group presented with no adequate earliest activation time at the two-sided BIS and epicardial coronary system [right: 7.79 ± 2.38 vs. left: 7.16 ± 2.59 vs. the middle cardiac vein (MCV): 6.26 ± 1.73 ms, P = 0.173] and poor-matched pacing-produced QRS at each site. Under the intracardiac echocardiography view, the pyramidal base was the broadest part of the septum and served as the division of the two-sided BIS. Focal ablation yielded promising acute-term and long-term procedural success in the LV-BIS and RV-BIS groups. But for the Intra group, VAs disappeared only after stepwise ablation successively targeted early preferential exit. After follow-up, three patients in the Intra group had recurrent VA, and all of them were treated well by a redo procedure or drug therapy., Conclusion: Intramural VAs were relatively common in the BIS region in our series. Intra-procedural mapping was important to distinguish the intramural VAs from other VAs by comparing the local activation time and pacing mapping. Procedural success could be achieved by stepwise ablation on the counterpart sides of the BIS and within the MCV., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: Non-invasive left ventricular (LV) pressure-strain loops provide a novel method for quantifying myocardial work by incorporating LV pressure in measurements of myocardial deformation. Early studies suggest that myocardial work parameters such as global constructive work (GCW) could be useful and reliable in arrhythmia prediction, particularly in patients undergoing cardiac resynchronization therapy (CRT). The aim of this study was to evaluate whether the magnitude of GCW was associated with the occurrence of ventricular arrhythmias in patients after CRT., Methods and Results: Patients on guideline-recommended treatment with a CRT defibrillator (CRT-D) were evaluated by 2D speckle-tracking echocardiography including measurements of GCW at least 6 months after implantation. The primary outcome was a composite of appropriate defibrillator therapy and sustained ventricular arrhythmia under the monitor zone. A total of 162 patients [mean age 66 years (±10), 122 males (75%)] were included. Sixteen (10%) patients experienced the primary outcome during a median follow-up of 18 months (interquartile range: 12-25) after the performance of index echocardiography. Patients with a below-median GCW (<1473 mmHg%) had a hazard ratio (HR) for the outcome of 8.14 [95% confidence interval (CI): 1.83-36.08], P = 0.006 compared with patients above the median in a univariate model and remained an independent predictor after multivariate adjustment for the estimated glomerular filtration rate and QRS duration [HR 4.75 (95% CI: 1.01-22.28), P < 0.05]., Conclusion: In patients treated with CRT-D, a GCW below median level was associated with a five-fold increase in the risk of ventricular arrhythmias., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aims: An automated method for determination of short-term variability (STV) of repolarization on intracardiac electrograms (STV-ARIauto) has previously been developed for arrhythmic risk monitoring by cardiac implantable devices, and has proved effective in predicting ventricular arrhythmias (VA) and guiding preventive high-rate pacing (HRP) in a canine model. Current study aimed to assess (i) STV-ARIauto in relation to VA occurrence and secondarily (ii-a) to confirm the predictive capacity of STV from the QT interval and (ii-b) explore the effect of HRP on arrhythmic outcomes in a porcine model of acute myocardial infarction (MI)., Methods and Results: Myocardial infarction was induced in 15 pigs. In 7/15 pigs, STV-QT was assessed at baseline, occlusion, 1 min before VA, and just before VA. Eight of the 15 pigs were additionally monitored with an electrogram catheter in the right ventricle, underwent echocardiography at baseline and reperfusion, and were randomized to paced or control group. Paced group received atrial pacing at 20 beats per min faster than sinus rhythm 1 min after occlusion. Short-term variability increased prior to VA in both STV modalities. The percentage change in STV from baseline to successive timepoints correlated well between STV-QT and STV-ARIauto. High-rate pacing did not improve arrhythmic outcomes and was accompanied by a stronger decrease in ejection fraction., Conclusion: STV-ARIauto values increase before VA onset, alike STV-QT in a porcine model of MI, indicating imminent arrhythmias. This highlights the potential of automatic monitoring of arrhythmic risk by cardiac devices through STV-ARIauto and subsequently initiates preventive strategies. Continuous HRP during onset of acute MI did not improve arrhythmic outcomes., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

In the last 25 years, EP Europace has published more than 300 basic and translational science articles covering different arrhythmia types (ranging from atrial fibrillation to ventricular tachyarrhythmias), different diseases predisposing to arrhythmia formation (such as genetic arrhythmia disorders and heart failure), and different interventional and pharmacological anti-arrhythmic treatment strategies (ranging from pacing and defibrillation to different ablation approaches and novel drug-therapies). These studies have been conducted in cellular models, small and large animal models, and in the last couple of years increasingly in silico using computational approaches. In sum, these articles have contributed substantially to our pathophysiological understanding of arrhythmia mechanisms and treatment options; many of which have made their way into clinical applications. This review discusses a representative selection of EP Europace manuscripts covering the topics of pacing and ablation, atrial fibrillation, heart failure and pro-arrhythmic ventricular remodelling, ion channel (dys)function and pharmacology, inherited arrhythmia syndromes, and arrhythmogenic cardiomyopathies, highlighting some of the advances of the past 25 years. Given the increasingly recognized complexity and multidisciplinary nature of arrhythmogenesis and continued technological developments, basic and translational electrophysiological research is key advancing the field. EP Europace aims to further increase its contribution to the discovery of arrhythmia mechanisms and the implementation of mechanism-based precision therapy approaches in arrhythmia management., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: Premature ventricular beats (PVBs) in athletes are often benign, but sometimes they may be a sign of an underlying disease. We evaluated the prevalence, burden, and morphology of PVBs in healthy voluntary athletes and controls with the main purpose of defining if certain PVB patterns are 'common' and 'training related' and, as such, are more likely benign., Methods and Results: We studied 433 healthy competitive athletes [median age 27 (18-43) years, 74% males] and 261 age- and sex-matched sedentary subjects who volunteered to undergo 12-lead 24 h ambulatory electrocardiogram (ECG) monitoring (24H ECG), with a training session in athletes. Ventricular arrhythmias (VAs) were evaluated in terms of their number, complexity [i.e. couplet, triplet, or non-sustained ventricular tachycardia (NSVT)], exercise inducibility, and morphology. Eighty-six percent of athletes and controls exhibited a total of ≤10 PVBs/24 h, and >90% did not show any couplets, triplets, or runs of NSVT > 3 beats. An higher number of PVBs correlated with increasing age (P < 0.01) but not with sex and level of training. The most frequent morphologies among the 36 athletes with >50 PVBs were the infundibular (44%) and fascicular (22%) ones. In a comparison between athletes and sedentary individuals, and male and female athletes, no statistically significant differences were found in PVBs morphologies., Conclusion: The prevalence and complexity of VAs at 24H ECG did not differ between athletes and sedentary controls and were not related to the type and amount of sport or sex. Age was the only variable associated with an increased PVB burden. Thus, no PVB pattern in the athlete can be considered 'common' or 'training related'., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Sudden cardiac death and ventricular arrhythmias are a global health issue. Recently, a new guideline for the management of ventricular arrhythmias and prevention of sudden cardiac death has been published by the European Society of Cardiology that serves as an update to the 2015 guideline on this topic. This review focuses on 10 novel key aspects of the current guideline: As new aspects, public basic life support and access to defibrillators are guideline topics. Recommendations for the diagnostic evaluation of patients with ventricular arrhythmias are structured according to frequently encountered clinical scenarios. Management of electrical storm has become a new focus. In addition, genetic testing and cardiac magnetic resonance imaging significantly gained relevance for both diagnostic evaluation and risk stratification. New algorithms for antiarrhythmic drug therapy aim at improving safe drug use. The new recommendations reflect increasing relevance of catheter ablation of ventricular arrhythmias, especially in patients without structural heart disease or stable coronary artery disease with only mildly impaired ejection fraction and haemodynamically tolerated ventricular tachycardias. Regarding sudden cardiac death risk stratification, risk calculators for laminopathies, and long QT syndrome are now considered besides the already established risk calculator for hypertrophic cardiomyopathy. Generally, 'new' risk markers beyond left ventricular ejection fraction are increasingly considered for recommendations on primary preventive implantable cardioverter defibrillator therapy. Furthermore, new recommendations for diagnosis of Brugada syndrome and management of primary electrical disease have been included. With many comprehensive flowcharts and practical algorithms, the new guideline takes a step towards a user-oriented reference book., Competing Interests: Conflict of interest: We disclose that in the past 2 years, L.E. received lecture fees from Abbott, Bayer, Boston Scientific, Daichii Sankyo, Medtronic, Biotronik, Sanofi Aventis, Bristol Myers Squibb. K.Z. received funding from Biosense Webster for research in electrophysiology. J.L.M. received direct payment for his personal services from Sanofi Aventis, Boston Scientific, Medtronic and Microport and research funding from Abbott, Daichii Sankyo, Biotronik and Milestone, his department received payment from Biosense, Abbott, Boston Scientific, Medtronic and Biotronik. C.S. received direct payment for his personal services from Biosense Webster, Abbott, Microport, Boston Scientific, Medtronic and Biotronik, travel, and meeting support from Biotronik and research funding from Medtronic. J.T.-H. received travel and meeting support from Abbott and Medtronic and direct personal payment from Leo Pharma. N.D. and H.K. disclose that there is no possible conflict of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: Ablation of outflow tract ventricular arrhythmias may be limited by a deep intramural location of the arrhythmogenic source. This study evaluates the acute and long-term outcomes of patients undergoing ablation of intramural outflow tract premature ventricular complexes (PVCs)., Methods and Results: This multicenter series included patients with structurally normal heart or nonischemic cardiomyopathy and intramural outflow tract PVCs defined by: (a) ≥ 2 of the following criteria: (1) earliest endocardial or epicardial activation < 20ms pre-QRS; (2) Similar activation in different chambers; (3) no/transient PVC suppression with ablation at earliest endocardial/epicardial site; or (b) earliest ventricular activation recorded in a septal coronary vein. Ninety-two patients were included, with a mean PVC burden of 21.5±10.9%. Twenty-six patients had had previous ablations. All PVCs had inferior axis, with LBBB pattern in 68%. In 29 patients (32%) direct mapping of the intramural septum was performed using an insulated wire or multielectrode catheter, and in 13 of these cases the earliest activation was recorded within a septal vein. Most patients required special ablation techniques (one or more), including sequential unipolar ablation in 73%, low-ionic irrigation in 26%, bipolar ablation in 15% and ethanol ablation in 1%. Acute PVC suppression was achieved in 75% of patients. Following the procedure, the PVC burden was reduced to 5.8±8.4%. The mean follow-up was 15±14 months and 16 patients underwent a repeat ablation., Conclusion: Ablation of intramural PVCs is challenging; acute arrhythmia elimination is achieved in 3/4 patients, and non-conventional approaches are often necessary for success., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: A pathogenic/likely pathogenic (P/LP) variant in SCN5A is found in 20-25% of patients with Brugada syndrome (BrS). However, the diagnostic yield and prognosis of gene panel testing in paediatric BrS is unclear. The aim of this study is to define the diagnostic yield and outcomes of SCN5A gene testing with ACMG variant classification in paediatric BrS patients compared with adults., Methods and Results: All consecutive patients diagnosed with BrS, between 1992 and 2022, were prospectively enrolled in the UZ Brussel BrS registry. Inclusion criteria were: (i) BrS diagnosis; (ii) genetic analysis performed with a large gene panel; and (iii) classification of gene variants following ACMG guidelines. Paediatric patients were defined as ≤16 years of age. The primary endpoint was ventricular arrhythmias (VAs). A total of 500 BrS patients were included, with 63 paediatric patients and 437 adult patients. Among children with BrS, 29 patients (46%) had a P/LP variant (P+) in SCN5A and no variants were found in 34 (54%) patients (P-). After a mean follow-up of 125.9 months, 8 children (12.7%) experienced a VA, treated with implanted cardioverter defibrillator shock. At survival analysis, P- paediatric patients had higher VA-free survival during the follow-up, compared with P+ paediatric patients. P+ status was an independent predictor of VA. There was no difference in VA-free survival between paediatric and adult BrS patients for both P- and P+., Conclusion: In a large BrS cohort, the diagnostic yield for P/LP variants in the paediatric population is 46%. P+ children with BrS have a worse arrhythmic prognosis., Competing Interests: Conflict of interest: A.B. is a consultant for Biotronik. A.S. received research grants from Daiichi-Sankyo and Bayer; he has received speaker fees from Menarini and Bayer. V.M. received an educational grant from the Foundation ‘Enrico and Enrica Sovena’. M.L.M. is consultant for Atricure. P.B. received compensation for teaching purposes from Biotronik. G.B.C. received compensation for teaching purposes and proctoring from Medtronic, Abbott, Biotronik, Boston Scientific, and Acutus Medical. C.d.A. receives research grants on behalf of the centre from Biotronik, Medtronic, Abbott, LivaNova, Boston Scientific, AtriCure, Philips, and Acutus; C.d.A. received compensation for teaching purposes and proctoring from Medtronic, Abbott, Biotronik, LivaNova, Boston Scientific, Atricure, Acutus Medical Daiichi Sankyo. The remaining authors have nothing to disclose., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Objectives: Aim of this study was to evaluate arrhythmic burden of patients with Barlow's disease and significant mitral regurgitation (MR) and assess the impact of mitral repair on ventricular arrhythmias (VA) in this group of subjects., Methods: We prospectively included 88 consecutive patients with Barlow's disease referred to our Institution from February 2021 to May 2022. All enrolled patients underwent 24-h Holter monitoring before surgery. Sixty-three of them completed 3 months echocardiographic and Holter follow-up. Significant arrhythmic burden was defined as ≥1% premature ventricular beats/24 h or at least one episode of non-sustained ventricular tachycardia (VT), VT or ventricular fibrillation., Results: At baseline, 29 patients (33%) were arrhythmogenic (AR), while 59 (67%) were not [non-arrhythmogenic (NAR)]. AR subjects tended to be more often females with history of palpitations. Sixty-three patients completed 3-months follow-up. Twenty of them (31.7%) were AR at baseline and 43 (68.3%) were not. Among AR patients, 9 (45%) remained AR after mitral surgery, while 11 (55%) became NAR. Considering NAR subjects at baseline, after mitral valve repair 8 (18.6%) evolved into AR, while 35 (81.4%) remained NAR. A higher prevalence of pre-operative MAD was found among patients experiencing VA reduction if compared with patients who remained arrhythmogenic (63.6% vs 11.1%, P = 0.028)., Conclusions: In our experience, one-third of Barlow's patients referred for mitral surgery showed a significant arrhythmic burden. Almost half of the subjects arrhythmogenic at baseline were free from significant VA after mitral repair. However, a minority (18.6%) of subjects without arrhythmic burden at baseline experienced significant VA at follow-up., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Electrical storm (ES) is a life-threatening condition characterized by at least three separate episodes of ventricular arrhythmias (VAs) over 24 h, each requiring therapeutic intervention, including implantable cardioverter defibrillator (ICD) therapies. Patients with ICDs in secondary prevention are at higher risk of ES and the most common presentation is that of scar-related monomorphic VAs. Electrical storm represents a major unfavourable prognostic marker in the history of patients with structural heart disease, with an associated two- to five-fold increase in mortality, heart transplant, and heart failure hospitalization. Early recognition and prompt treatment are crucial to improve the outcome. Yet, ES management is complex and requires a multidisciplinary approach and well-defined protocols and networks to guarantee a proper patient care. Acute phase stabilization should include a comprehensive clinical assessment, resuscitation and sedation management skills, ICD reprogramming, and acute sympathetic modulation, while the sub-acute/chronic phase requires a comprehensive heart team evaluation to define the better treatment option according to the haemodynamic and overall patient's condition and the type of VAs. Advanced anti-arrhythmic strategies, not mutually exclusive, include invasive ablation, cardiac sympathetic denervation, and, for very selected cases, stereotactic ablation. Each of these aspects, as well as the new European Society of Cardiology guidelines recommendations, will be discussed in the present review., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Brugada syndrome is an inherited channelopathy with an increased risk of sudden cardiac death (SCD) due to ventricular arrhythmias (VA) and an increased incidence of supraventricular arrhythmias, as compared with the general population. For the prevention of SCD, the guidelines recommend the implantable cardioverter-defibrillator (ICD); however, ICD does not prevent VA. In this article, we provide a brief review of the literature on the Brugada syndrome pharmacological therapy, mainly focusing on quinidine treatment. The efficacy of quinidine therapy in the prevention of VA in Brugada syndrome has been demonstrated by several small studies in patients with ICD and recurrent shocks or in asymptomatic patients with inducible ventricular fibrillation (VF) at electrophysiological study. Quinidine has also been tested for the prophylaxis of supraventricular arrhythmias, especially atrial fibrillation/flutter, and in paediatric patients. In these studies, quinidine proved highly effective in preventing re-induction of VF and spontaneous recurrences of both ventricular and supraventricular arrhythmias. Unfortunately, this therapy is burdened by a high incidence of side effects, which may lead to drug discontinuation., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Electrical storm (ES) is a predictor of mortality, and its treatment is challenging. Moreover, not all potential therapeutic strategies are available in all hospitals, and a standardized approach among European centres is lacking. The aim of this European Heart Rhythm Association (EHRA) survey was to assess the current management of patients with ES both in the acute and post-acute phases in 102 different European centres. A 20-item online questionnaire was sent out to the EHRA Research Network Centres. The median number of patients with ES treated annually per centre is 10 (IQR 5-15). The possibility of using autonomic modulation (e.g. percutaneous stellate ganglion block or thoracic epidural anaesthesia) for the acute ES treatment is available in only 29.3% of the centres. Moreover, although over 80% of centres perform ventricular tachycardia ablation, this procedure is available 24/7 in only 16.5% of the hospitals. There is a significant heterogeneity among centres regarding the availability of AADs and their use before deciding to proceed with a non-AAD strategy; specifically, 4.4% of centres use only one drug, 33.3% use two drugs, and 12.2% >two drugs, while about 50% of the centres decide based on individual patient's characteristics. Regarding the type of AADs used for the acute and post-acute management of ES patients, important variability is reported depending upon the underlying heart disease. Most patients considered for percutaneous ablation have structural heart disease. Only 46% of centres refer patients to psychological counselling after ES., Competing Interests: Conflict of interest: M.M.F. received speaker and proctoring fees from Medtronic Poland and Abbott Poland. The other authors report no conflicts of interest related specifically to this manuscript., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: To evaluate whether cardiac magnetic resonance (CMR)-based parametric mapping and strain analysis can improve the risk-stratification for ventricular arrhythmias (VA) and sudden death (SD) in non-ischaemic cardiomyopathy (NICM)., Methods and Results: Secondary analysis of a prospective single-centre-registry (NCT02326324), including 703 consecutive NICM patients, 618 with extracellular volume (ECV) available. The combined primary endpoint included appropriate implantable cardioverter defibrillator therapies, sustained ventricular tachycardia, resuscitated cardiac arrest and SD. During a median follow-up of 21 months, 14 patients (2%) experienced the primary endpoint. Native T1 was not associated with the primary endpoint. Left ventricular global longitudinal strain lost its significant association after adjustment for left ventricular ejection fraction (LVEF). Among patients with ECV available, 11 (2%) reached the primary endpoint. Mean ECV was significantly associated with the primary endpoint and the best cut-off was 30%. ECV ≥ 30% was the strongest independent predictor of the primary endpoint (hazard ratio 14.1, P = 0.01) after adjustment for late gadolinium enhancement (LGE) and LVEF. ECV ≥ 30% discriminated the arrhythmic risk among LGE+ cases and among those with LVEF ≤ 35%. A simple clinical risk-stratification model, based on LGE, LVEF ≤ 35% and ECV ≥ 30%, achieved an excellent predictive ability (Harrell's C 0.82) and reclassified the risk of 32% of the study population as compared to LVEF ≤ 35% alone., Conclusions: Comprehensive CMR evaluation in NICM showed that ECV was the only parameter with an independent and strong predictive value for VA/SD, on top of LGE and LVEF. A risk-stratification model based on LGE, LVEF ≤ 35% and ECV ≥ 30% achieved an excellent predictive ability for VA/SD., Clinical Trial Registration: UHSM CMR study (NCT02326324) https://clinicaltrials.gov/ct2/show/NCT02326324., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Aims: To evaluate the baseline characteristics and the prognostic implications associated with late gadolinium enhancement limited to the right ventricular insertion points (IP-LGE) or present at both the right ventricular insertion points and the left ventricle (IP&LV-LGE) in non-ischaemic dilated cardiomyopathy (DCM)., Methods and Results: This is a retrospective observational multicentre cohort study including 1165 consecutive patients with DCM evaluated by cardiac magnetic resonance. The primary endpoint included appropriate defibrillator therapies, sustained ventricular tachycardia, resuscitated cardiac arrest, or sudden death. The secondary outcome encompassed heart failure hospitalizations, heart transplant, left ventricular assist device implantation, and end-stage heart failure death. IP-LGE was found in 72 patients (6%), who had clinical characteristics closer to LGE- than to LGE+ patients. During follow-up (median 36 months), none of the IP-LGE patients experienced the primary endpoint. The cumulative incidence of the primary endpoint was similar between IP-LGE and LGE- patients (P = 1), while IP-LGE had significantly lower cumulative incidence when compared with LGE+ patients (P < 0.001). When compared with IP-LGE patients, the cumulative incidence of the secondary endpoint was similar in LGE- cases (P = 0.86) but tended to be higher in LGE+ patients (P = 0.06). Both clinical characteristics and outcomes were similar between IP&LV-LGE patients and the rest of LGE+ cases., Conclusions: In a large cohort of DCM patients, IP-LGE was associated with similar outcome when compared with LGE- patients and with significant lower risk of ventricular arrhythmias and sudden death when compared with LGE+ cases. Patients with IP&LV-LGE had clinical characteristics and outcomes similar to the rest of LGE+ cases., Competing Interests: Conflict of interest: P.F.B. received a fellowship salary support grant from Alliance Medical. There is no other conflict of interest for the present study., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Aims: Altered ventricular activation (AVA) causes intraventricular mechanical dyssynchrony (MD) and impedes contraction, promoting pro-arrhythmic electrical remodelling in the chronic atrioventricular block (CAVB) dog. We aimed to study arrhythmogenic and electromechanical outcomes of different degrees of AVA., Methods and Results: Following atrioventricular block, AVA was established through idioventricular rhythm (IVR; n = 29), right ventricular apex (RVA; n = 12) pacing or biventricular pacing [cardiac resynchronization therapy (CRT); n = 10]. After ≥3 weeks of bradycardic remodelling, Torsade de Pointes arrhythmia (TdP) inducibility, defined as ≥3 TdP/10 min, was tested with specific IKr-blocker dofetilide (25 μg/kg/5 min). Mechanical dyssynchrony was assessed by echocardiography as time-to-peak (TTP) of left ventricular (LV) free-wall minus septum (ΔTTP). Electrical intraventricular dyssynchrony was assessed as slope of regression line correlating intraventricular LV activation time (AT) and activation recovery interval (ARI). Under sinus rhythm, contraction occurred synchronous (ΔTTP: -8.6 ± 28.9 ms), and latest activated regions seemingly had slightly longer repolarization (AT-ARI slope: -0.4). Acute AV block increased MD in all groups, but following ≥3 weeks of remodelling IVR animals became significantly more TdP inducible (19/29 IVR vs. 5/12 RVA and 2/10 CRT, both P < 0.05 vs. IVR). After chronic AVA, intraventricular MD was lowest in CRT animals (ΔTTP: -8.5 ± 31.2 vs. 55.80 ± 20.0 and 82.7 ± 106.2 ms in CRT, IVR, and RVA, respectively, P < 0.05 RVA vs. CRT). Although dofetilide steepened negative AT-ARI slope in all groups, this heterogeneity in dofetilide-induced ARI prolongation seemed least pronounced in CRT animals (slope to -0.8, -3.2 and -4.5 in CRT, IVR and RVA, respectively)., Conclusion: Severity of intraventricular MD affects the extent of electrical remodelling and pro-arrhythmic outcome in the CAVB dog model., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

To develop a suite of quality indicators (QIs) for the management of patients with ventricular arrhythmias (VA) and the prevention of sudden cardiac death (SCD). The Working Group comprised experts in heart rhythm management including Task Force members of the 2022 European Society of Cardiology (ESC) Clinical Practice Guidelines for the management of patients with VA and the prevention of SCD, members of the European Heart Rhythm Association, international experts, and a patient representative. We followed the ESC methodology for QI development, which involves (i) the identification of the key domains of care for the management of patients with VA and the prevention of SCD by constructing a conceptual framework of care, (ii) the development of candidate QIs by conducting a systematic review of the literature, (iii) the selection of the final set of QIs using a modified-Delphi method, and (iv) the evaluation of the feasibility of the developed QIs. We identified eight domains of care for the management of patients with VA and the prevention of SCD: (i) structural framework, (ii) screening and diagnosis, (iii) risk stratification, (iv) patient education and lifestyle modification, (v) pharmacological treatment, (vi) device therapy, (vii) catheter ablation, and (viii) outcomes, which included 17 main and 4 secondary QIs across these domains. Following a standardized methodology, we developed 21 QIs for the management of patients with VA and the prevention of SCD. The implementation of these QIs will improve the care and outcomes of patients with VA and contribute to the prevention of SCD., Competing Interests: Conflict of interest: M.J.A. is a consultant for Abbott, Boston Scientific, Bristol Myers Squibb, Daichii Sankyo, Invitae, LQT Therapeutics, and Medtronic. M.J.A. and/or Mayo Clinic are involved in an equity/intellectual property/royalty relationship with AliveCor, Anumana, ARMGO Pharma, Pfizer, and UpToDate. However, none of these entities were involved in this study. T.D. receives from InHeart—Speaker honoraria, personal (< 5.000€), Siemens—Speaker Honoraria, institutional (< 5.000€), Biotronik—Educational Course Director, personal (< 10.000€), Abbott—Speaker honoraria, personal (< 5.000€) and Boston Scientific—Adverse events committee, personal (< 5.000€). CPG Chair of the Data Science Group of EuroHeart, Deputy Editor of EHJ Quality of Care and Clinical Outcomes. Unrelated to the present work: Research grants from Abbott, BMS, BHF, Horizon 2020, NIHR; speaker’s honoraria from AstraZeneca, Raisio Group, Wondr Medical; Consulting from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Ely-Lilly, Menarini, Vifor outside the submitted work., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Aims: While mexiletine has been used for over 40 years for prevention of (recurrent) ventricular arrhythmias and for myotonia, patient access has recently been critically endangered. Here we aim to demonstrate the effectiveness and safety of mexiletine in the treatment of patients with (recurrent) ventricular arrhythmias, emphasizing the absolute necessity of its accessibility., Methods and Results: Studies were included in this systematic review (PROSPERO, CRD42020213434) if the efficacy or safety of mexiletine in any dose was evaluated in patients at risk for (recurrent) ventricular arrhythmias with or without comparison with alternative treatments (e.g. placebo). A systematic search was performed in Ovid MEDLINE, Embase, and in the clinical trial registry databases ClinicalTrials.gov and ICTRP. Risk of bias were assessed and tailored to the different study designs. Large heterogeneity in study designs and outcome measures prompted a narrative synthesis approach. In total, 221 studies were included reporting on 8970 patients treated with mexiletine. Age ranged from 0 to 88 years. A decrease in ventricular arrhythmias of >50% was observed in 72% of the studies for pre-mature ventricular complexes, 64% for ventricular tachycardia, and 33% for ventricular fibrillation. Electrocardiographic effects of mexiletine were small; only in a subset of patients with primary arrhythmia syndromes, a relative (desired) QTc decrease was reproducibly observed. As for adverse events, gastrointestinal complaints were most frequently observed (33% of the patients)., Conclusions: In this systematic review, we present all the currently available knowledge of mexiletine in patients at risk for (recurrent) ventricular arrhythmias and show that mexiletine is both effective and safe., Competing Interests: Conflict of interest: P.G.P. is a member of the Scientific Advisory Group on Cardiovascular Issues (SAG-CVS) of the EMA since 2021. C.E.M.H. is involved in pre-marketing research with Sanofi, Protalix, and Idorsia, outside the submitted work. N.R., N.S., S.B., V.W., B.J., and C.E.M.H. are members of the platform ‘Medicijn voor de Maatschappij’. This is an academic initiative that aims to support sustainable access to medicines for rare diseases, including mexiletine. V.W. reports personal fees from Fair Medicine Foundation, personal fees from Patient One, outside the submitted work., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: Arrhythmogenic right ventricular cardiomyopathy (ARVC) causes ventricular arrhythmias (VAs) and sudden cardiac death (SCD). In 2019, a risk prediction model that estimates the 5-year risk of incident VAs in ARVC was developed (ARVCrisk.com). This study aimed to externally validate this prediction model in a large international multicentre cohort and to compare its performance with the risk factor approach recommended for implantable cardioverter-defibrillator (ICD) use by published guidelines and expert consensus., Methods and Results: In a retrospective cohort of 429 individuals from 29 centres in North America and Europe, 103 (24%) experienced sustained VA during a median follow-up of 5.02 (2.05-7.90) years following diagnosis of ARVC. External validation yielded good discrimination [C-index of 0.70 (95% confidence interval-CI 0.65-0.75)] and calibration slope of 1.01 (95% CI 0.99-1.03). Compared with the three published consensus-based decision algorithms for ICD use in ARVC (Heart Rhythm Society consensus on arrhythmogenic cardiomyopathy, International Task Force consensus statement on the treatment of ARVC, and American Heart Association guidelines for VA and SCD), the risk calculator performed better with a superior net clinical benefit below risk threshold of 35%., Conclusion: Using a large independent cohort of patients, this study shows that the ARVC risk model provides good prognostic information and outperforms other published decision algorithms for ICD use. These findings support the use of the model to facilitate shared decision making regarding ICD implantation in the primary prevention of SCD in ARVC., Competing Interests: Conflicts of interest: C.M.: honoraria from Abbott, I.O.: grants, consulting fees or honoraria from BSM, Cytokinetics, Shire, Genzyme, Amicus, Menarini International, Boston Scientific, and Tenaya, S.A.L.: grants from BMS/Pfizer, Boehringer Ingelheim, fitbit, IBM, and consulting fees from BMS/Pfizer, Invitae, and Blackstone, J.S.H.: research grants from Boston Scientific, Abbott, and Medtronic and is on Scientific Advisory Board for Boston Scientific, H.K.J.: grant from Novo Nordisk foundation and honoraria from Abbott and Biosense Webster, H.C.: consultant for Medtronic Inc., Biosense Webster, Pfizer, and Abbott. He receives research support from Boston Scientific Corp. C.A.J. receives salary support from this grant and consulting fees from Pfizer, J. C.-T. consulting fees from BMS/Pfizer and Bayer., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology.)

Aims: Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVC) is characterized by ventricular arrhythmias (VAs) and sudden cardiac death (SCD). We aimed to develop a model for individualized prediction of incident VA/SCD in ARVC patients., Methods and Results: Five hundred and twenty-eight patients with a definite diagnosis and no history of sustained VAs/SCD at baseline, aged 38.2 ± 15.5 years, 44.7% male, were enrolled from five registries in North America and Europe. Over 4.83 (interquartile range 2.44-9.33) years of follow-up, 146 (27.7%) experienced sustained VA, defined as SCD, aborted SCD, sustained ventricular tachycardia, or appropriate implantable cardioverter-defibrillator (ICD) therapy. A prediction model estimating annual VA risk was developed using Cox regression with internal validation. Eight potential predictors were pre-specified: age, sex, cardiac syncope in the prior 6 months, non-sustained ventricular tachycardia, number of premature ventricular complexes in 24 h, number of leads with T-wave inversion, and right and left ventricular ejection fractions (LVEFs). All except LVEF were retained in the final model. The model accurately distinguished patients with and without events, with an optimism-corrected C-index of 0.77 [95% confidence interval (CI) 0.73-0.81] and minimal over-optimism [calibration slope of 0.93 (95% CI 0.92-0.95)]. By decision curve analysis, the clinical benefit of the model was superior to a current consensus-based ICD placement algorithm with a 20.3% reduction of ICD placements with the same proportion of protected patients (P < 0.001)., Conclusion: Using the largest cohort of patients with ARVC and no prior VA, a prediction model using readily available clinical parameters was devised to estimate VA risk and guide decisions regarding primary prevention ICDs (www.arvcrisk.com)., Competing Interests: Conflict of interest: H.C. is a consultant for Medtronic Inc. and St. Jude Medical/Abbott. H.C. receives research support from Boston Scientific Corp. C.T. and C.A.J. receive salary support from this grant. C.A.J. has received funding for an invited lecture from Abbott. H.T. receives research support from Abbott. A.A.M.W. received a personal fee from Audentes 2017. A.M.S. received lecture honoraria from Boston Scientific Corp. S.L.Z. receives salary support as an advisor to Siemens Healthcare. D.P.J. is a consultant for Pfizer, GSK, and Blade Therapeutics, and receives research support from NIH, Eidos Therapeutics, and Array Biopharma. The rest of the authors have no conflicts of interest., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology.)

Aims: We aimed to characterize the substrate of T-wave inversion (TWI) using cardiac magnetic resonance (CMR) and the association between diffuse fibrosis and ventricular arrhythmias (VA) in patients with mitral valve prolapse (MVP)., Methods and Results: TWI was defined as negative T-wave ≥0.1 mV in ≥2 adjacent ECG leads. Diffuse myocardial fibrosis was assessed by T1 relaxation time and extracellular volume (ECV) fraction by T1-mapping CMR. We included 162 patients with MVP (58% females, age 50 ± 16 years), of which 16 (10%) patients had severe VA (aborted cardiac arrest or sustained ventricular tachycardia). TWI was found in 34 (21%) patients. Risk of severe VA increased with increasing number of ECG leads displaying TWI [OR 1.91, 95% CI (1.04-3.52), P = 0.04]. The number of ECG leads displaying TWI increased with increasing lateral ECV (26 ± 3% for TWI 0-1leads, 28 ± 4% for TWI 2leads, 29 ± 5% for TWI ≥3leads, P = 0.04). Patients with VA (sustained and non-sustained ventricular tachycardia) had increased lateral T1 (P = 0.004), also in the absence of late gadolinium enhancement (LGE) (P = 0.008)., Conclusions: Greater number of ECG leads with TWI reflected a higher arrhythmic risk and higher degree of lateral diffuse fibrosis by CMR. Lateral diffuse fibrosis was associated with VA, also in the absence of LGE. These results suggest that TWI may reflect diffuse myocardial fibrosis associated with VA in patients with MVP. T1-mapping CMR may help risk stratification for VA., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: Echocardiographic studies suggest that strain is related to myocardial fibrosis (MF) and ventricular arrhythmias (VA) in hypertrophic cardiomyopathy (HCM) patients. Cardiac magnetic resonance feature tracking (CMR-FT) also allows strain analysis, but little is known whether it provides incremental value to late gadolinium enhancement imaging (LGE). This study aimed to explore the relationship between CMR-FT-derived strain parameters and histopathology MF and VA and its incremental value to LGE in obstructive HCM (HOCM) patients undergoing septal myectomy., Methods and Results: One hundred and twenty-three symptomatic HOCM patients underwent CMR examination, followed by septal myectomy. The abnormally increased histological MF was defined as higher than the mean + 2 standard deviation (SD) of nine control autopsy subjects who had no history of cardiovascular disease. Septal strain parameters and septal LGE were evaluated at the site of surgical myectomy. Among HOCM patients without LGE, septal circumferential (P = 0.003), longitudinal (P = 0.001), and radial (P = 0.02) strains were significantly impaired in patients with increased histological MF than those without. Histological MF was significantly associated with septal circumferential strain (r = 0.32, P < 0.001), septal longitudinal strain (r = 0.42, P < 0.001), and septal radial strain (r = -0.27, P = 0.003). On multivariate analysis, septal longitudinal strain was independently associated with histological MF [β, 0.19 (0.05-0.34); P = 0.01], and VA [odds ratio, 1.10 (1.01-1.19); P = 0.02]. Moreover, septal longitudinal strain was incremental to septal %LGE in detecting increased MF (P = 0.001) and VA (P = 0.048)., Conclusions: Septal longitudinal strain at CMR is independently related to histological MF and occurrence of VA in HOCM patients. Moreover, it provides incremental value over LGE in detecting increased MF and VA., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2022. For permissions, please email: journals.permissions@oup.com.)

On behalf of the European Heart Rhythm Association, we designed a survey, whose aim was to understand the trend(s) in the clinical management of idiopathic monomorphic premature ventricular contractions (PVCs) among European cardiologists and cardiac electrophysiologists. A total of 202 participants in the survey answered 27 multiple-choice questions on the clinical presentation, diagnosis and treatment of idiopathic monomorphic PVCs. The most common symptom in patients with idiopathic monomorphic PVCs is palpitations, according to the majority of responders (87%), followed by fatigue (29%) and dizziness (18%). Complete blood cell count, renal function with electrolytes levels, and thyroid function are the blood tests requested by the majority of respondents (65%, 92%, and 93%, respectively). Coronary artery disease and structural heart disease needs to be ruled out, according to the vast majority of participants (99%). A 24-h Holter ECG is the preferred ECG modality to assess the burden of PVCs (86% of respondents). Among the different option treatments, beta-blockers and class I antiarrhythmic drugs are by far (81% of respondents) the preferred pharmacological option in comparison with calcium antagonists and class III antiarrhythmic drugs. Catheter ablation has also a good reputation: 99% of responders are keen to use it, especially in patients with high burden of PVCs and when signs of cardiomyopathy occur., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2022. For permissions, please email: journals.permissions@oup.com.)

Aims: To non-invasively characterize, by means of late gadolinium enhancement cardiac magnetic resonance (LGE-CMR), scar differences, and potential variables associated with ventricular tachycardia (VT) occurrence in chronic post-myocardial infarction (MI) patients., Methods and Results: A case-control study was designed through retrospective LGE-CMR data analysis of chronic post-MI patients (i) consecutively referred for VT substrate ablation after a first VT episode (n = 66) and (ii) from a control group (n = 84) with no arrhythmia evidence. The myocardium was characterized differentiating core, border zone (BZ), and BZ channels (BZCs) using the ADAS 3D post-processing imaging platform. Clinical and scar characteristics, including a novel parameter, the BZC mass, were compared between both groups. One hundred and fifty post-MI patients were included. Four multivariable Cox proportional hazards regression models were created for total scar mass, BZ mass, core mass, and BZC mass, adjusting them by age, sex, and left ventricular ejection fraction (LVEF). A cut-off of 5.15 g of BZC mass identified the cases with 92.4% sensitivity and 86.9% specificity [area under the ROC curve (AUC) 0.93 (0.89-0.97); P < 0.001], with a significant increase in the AUC compared to other scar parameters (P < 0.001 for all pairwise comparisons). Adding BZC mass to LVEF allowed to reclassify 33.3% of the cases and 39.3% of the controls [net reclassification improvement = 0.73 (0.71-0.74)]., Conclusions: The mass of BZC is the strongest independent variable associated with the occurrence of sustained monomorphic ventricular tachycardia in post-MI patients after adjustment for age, sex, and LVEF. Border zone channel mass measurement could permit a more accurate VT risk stratification than LVEF in chronic post-MI patients., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Aims: Bipolar radiofrequency ablation (B-RFA) has been reported as a bail-out strategy for the treatment of therapy refractory ventricular arrhythmias (VA). Currently, existing setups have not been standardized for B-RFA, while the impact of conventional B-RFA approaches on lesion formation remains unclear., Methods and Results: (i) In a multicentre observational study, patients undergoing B-RFA for previously therapy-refractory VA using a dedicated B-RFA setup were retrospectively analysed. (ii) Additionally, in an ex vivo model lesion formation during B-RFA was evaluated using porcine hearts. In a total of 26 procedures (24 patients), acute success was achieved in all 14 ventricular tachycardia (VT) procedures and 7/12 procedures with premature ventricular contractions (PVC), with major complications occurring in 1 procedure (atrioventricular block). During a median follow-up of 211 days in 21 patients, 6/11 patients (VT) and 5/10 patients (PVC) remained arrhythmia-free. Lesion formation in the ex vivo model during energy titration from 30 to 50 W led to similar lesion volumes compared with initial high-power 50 W B-RFA. Lesion size significantly increased when combining sequential unipolar and B-RFA (1429 mm3 vs. titration 501 mm3 vs. B-RFA 50 W 423 mm3, P < 0.001), an approach used in overall 58% of procedures and more frequently applied in procedures without VA recurrence (92% vs. 36%, P = 0.009). Adipose tissue severely limited lesion formation during B-RFA., Conclusion: Using a dedicated device for B-RFA for therapy-refractory VA appears feasible and safe. While some patients need repeat ablation, success rates were encouraging. Sequential unipolar and B-RFA may be favourable for lesion formation., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)