Journal: Europace

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Abstract

First experience with pulsed field ablation as routine treatment for paroxysmal atrial fibrillation.

Füting A, Reinsch N, Höwel D, Brokkaar L, Rahe G, Neven K
Aims
Catheter ablation for atrial fibrillation (AF) using thermal energy can cause collateral damage. Pulsed field ablation (PFA) is a novel non-thermal energy source. Few small clinical studies have been published. We report on the first \'real-world\' experience with pulmonary vein isolation (PVI) using PFA for paroxysmal AF (PAF).
Methods and results
Pre- and post-ablation, phrenic nerve function was assessed. After high-density left atrial (LA) bipolar voltage mapping, all PVs were individually isolated using a 13 Fr steerable sheath and a pentaspline PFA over-the-wire catheter. After ablation, bipolar voltage mapping was repeated to assess lesion formation. In 30 PAF patients (mean 63 years; 53% female), uncomplicated PFA was performed, with all PVs acutely isolated. The median procedure time was 116 min. The median PFA catheter LA dwell time was 29 min. The median fluoroscopy time was 26 min. In one patient with roof-dependent flutter, a roof line was intentionally created. In two patients, unintentional bidirectional mitral isthmus block was created. There was no phrenic nerve or oesophageal damage. In one patient, pericardial drainage after cardiac tamponade was performed. In-hospital stay and 30-day follow-up were uneventful. After 90 days, 97% of patients were in sinus rhythm.
Conclusion
PVI using PFA for PAF in a \'real-world\' setting appears to be safe and feasible in this small patient cohort. Procedure times are homogeneous, and LA dwell time is short. Atrial ablation lines can easily be created. Unintentional ablation of atrial tissue can occur, accurate catheter alignment to the PV ostium and axis should be ensured.

© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Europace: 06 May 2022; epub ahead of print
Füting A, Reinsch N, Höwel D, Brokkaar L, Rahe G, Neven K
Europace: 06 May 2022; epub ahead of print | PMID: 35513354
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Abstract

Perceived vs. objective frailty in patients with atrial fibrillation and impact on anticoagulant dosing: an ETNA-AF-Europe sub-analysis.

Diemberger I, Fumagalli S, Mazzone AM, Bakhai A, ... Kirchhof P, De Caterina R
Aims
Frailty is common in patients with atrial fibrillation (AF), with possible impact on therapies and outcomes. However, definitions of frailty are variable, and may not overlap with frailty perception among physicians. We evaluated the prevalence of frailty as perceived by enrolling physicians in the Edoxaban Treatment in Routine Clinical Practice for Patients With Non-Valvular AF (ETNA-AF)-Europe registry (NCT02944019), and compared it with an objective frailty assessment.
Methods and results
ETNA-AF-Europe is a prospective, multi-centre, post-authorization, observational study. There we assessed the presence of frailty according to (i) a binary subjective investigators\' judgement and (ii) an objective measure, the Modified Frailty Index. Baseline data on frailty were available in 13 621/13 980 patients. Prevalence of perceived frailty was 10.6%, with high variability among participating countries and healthcare settings (range 5.9-19.6%). Conversely, only 5.0% of patients had objective frailty, with minimal variability (range 4.5-6.7%); and only <1% of patients were identified as frail by both approaches. Compared with non-frailty-perceived, perceived frail patients were older, more frequently female, and with lower body weight; conversely, objectively frail patients had more comorbidities. Non-recommended edoxaban dose regimens were more frequently prescribed in both frail patient categories.
Conclusions
Physicians\' perception of frailty in AF patients is variable, mainly driven by age, sex, and weight, and quite different compared with the results of an objective frailty assessment. Whatever the approach, frailty appears to be associated with non-recommended anticoagulant dosages. Whether this apparent inappropriateness influences hard outcomes remains to be assessed.

© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.

Europace: 04 May 2022; epub ahead of print
Diemberger I, Fumagalli S, Mazzone AM, Bakhai A, ... Kirchhof P, De Caterina R
Europace: 04 May 2022; epub ahead of print | PMID: 35512229
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Abstract

Cardiac ablation with pulsed electric fields: principles and biophysics.

Sugrue A, Maor E, Del-Carpio Munoz F, Killu AM, Asirvatham SJ
Pulsed electric fields (PEFs) have emerged as an ideal cardiac ablation modality. At present numerous clinical trials in humans are exploring PEF as an ablation strategy for both atrial and ventricular arrhythmias, with early data showing significant promise. As this is a relatively new technology there is limited understanding of its principles and biophysics. Importantly, PEF biophysics and principles are starkly different to current energy modalities (radiofrequency and cryoballoon). Given the relatively novel nature of PEFs, this review aims to provide an understanding of the principles and biophysics of PEF ablation. The goal is to enhance academic research and ultimately enable optimization of ablation parameters to maximize procedure success and minimize risk.

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Europace: 15 Apr 2022; epub ahead of print
Sugrue A, Maor E, Del-Carpio Munoz F, Killu AM, Asirvatham SJ
Europace: 15 Apr 2022; epub ahead of print | PMID: 35426908
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Abstract

Nationwide study of mortality and sudden cardiac death in young persons diagnosed with chronic kidney disease.

Svane J, Nielsen JL, Stampe NK, Feldt-Rasmussen B, ... Lynge TH, Tfelt-Hansen J
Aims
The aim of this study was to compare short- and long-term risk of sudden cardiac death (SCD) among persons aged 18-49 years with and without chronic kidney disease (CKD).
Methods and results
Using Danish nationwide health registries, all persons aged 18-49 years diagnosed with earlier stages of CKD or chronic kidney failure from 1 July 1995 through 2009 were identified. Non-exposed subjects matched on sex and birth-year were identified. All SCD in the Danish population aged 18-49 years in 2000-2009 have previously been identified using information from the Danish nationwide health registries, death certificates, and autopsy reports. In total, 9308 incident cases of earlier stage CKD and 1233 incident cases of chronic kidney failure were included. Among patients with earlier stage CKD, the absolute risk of SCD 1, 5, and 10 years after diagnosis was 0.14%, 0.37%, and 0.68%, respectively. Compared with age- and sex-matched subjects the corresponding relative risk (RR) was 20.3 [95% confidence interval (CI) 8.4-48.8], 7.1 (95% CI 4.2-12.0), and 6.1 (95% CI 3.8-9.7), respectively. Among patients with chronic kidney failure, the absolute 1-, 5-, and 10-year risk of SCD was 0.17%, 0.56%, and 2.07%, respectively. The corresponding RR was 12.5 (95% CI 1.4-111.6), 7.9 (95% CI 2.3-27.0), and 10.1 (95% CI 4.5-22.6).
Conclusion
Persons with earlier stage CKD and chronic kidney failure had increased risk of SCD compared with the background population with a 6- to 20-fold increased risk of SCD. These findings underline the importance of early cardiovascular risk monitoring and assessment in persons with CKD.

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Europace: 04 Apr 2022; epub ahead of print
Svane J, Nielsen JL, Stampe NK, Feldt-Rasmussen B, ... Lynge TH, Tfelt-Hansen J
Europace: 04 Apr 2022; epub ahead of print | PMID: 35373838
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Abstract

Association between left atrial epicardial fat, left atrial volume, and the severity of atrial fibrillation.

van Rosendael AR, Smit JM, El\'Mahdiui M, van Rosendael PJ, ... Delgado V, Bax JJ
Aims
Left atrial (LA) volume and LA epicardial fat are both substrates for atrial fibrillation (AF), but may relate with AF at different (early vs. late) stages in the AF disease process. We evaluated associations between LA epicardial fat and LA volume in patients with sinus rhythm (SR), paroxysmal AF (PAF), and persistent/permanent AF.
Methods and results
In total, 300 patients (100 with SR, 100 with PAF, and 100 with persistent/permanent AF) who underwent cardiac computed tomography angiography (CTA) were included. The epicardial fat mass posterior to the LA and the LA volume were quantified from CTA and compared between patients with SR, PAF, and persistent/permanent AF. Furthermore, four groups were created by classifying LA epicardial fat and LA volume into large or small according to their median. The mean age of the population was 58.9 ± 10.5 years and 69.7% was male. Left atrial epicardial fat mass was larger in patients with PAF compared with SR, but did not further increase from PAF to persistent/permanent AF. Left atrial volume increased significantly from SR to PAF and to persistent/permanent AF. Left atrial epicardial fat and LA volume were both concordantly large or small in 184 (61%) patients, and discordant in 116 (39%). When both were small, 65.2% of the patients had SR, 23.9% PAF, and 10.9% persistent/permanent AF. When the LA epicardial fat mass was large and the LA volume small (compared with both being small), patients were significantly more often in PAF (55.2 vs. 23.9, P < 0.05), less frequently in SR (32.8% vs. 65.2%, P < 0.05) but showed comparable rates of persistent/permanent AF (12.0% vs. 10.9%, P < 0.05). When the LA volume was large, most patients had persistent/permanent AF.
Conclusion
Left atrial epicardial fat mass was larger in PAF vs. SR, possibly indicating a marker of early disease, while large LA volumes were associated with a high prevalence of persistent/permanent AF. Elevated LA epicardial fat mass without large LA volume may reflect the early AF disease process.

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Europace: 31 Mar 2022; epub ahead of print
van Rosendael AR, Smit JM, El'Mahdiui M, van Rosendael PJ, ... Delgado V, Bax JJ
Europace: 31 Mar 2022; epub ahead of print | PMID: 35355079
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Abstract

The MADIT-ICD benefit score helps to select implantable cardioverter-defibrillator candidates in cardiac resynchronization therapy.

Dauw J, Martens P, Nijst P, Meekers E, ... Dupont M, Mullens W
Aims
The aim of this study is to evaluate whether the MADIT-ICD benefit score can predict who benefits most from the addition of implantable cardioverter-defibrillator (ICD) to cardiac resynchronization therapy (CRT) in real-world patients with heart failure with reduced ejection fraction (HFrEF) and to compare this with selection according to a multidisciplinary expert centre approach.
Methods and results
Consecutive HFrEF patients who received a CRT for a guideline indication at a tertiary care hospital (Ziekenhuis Oost-Limburg, Genk, Belgium) between October 2008 and September 2016, were retrospectively evaluated. The MADIT-ICD benefit groups (low, intermediate, and high) were compared with the current multidisciplinary expert centre approach. Endpoints were (i) sustained ventricular tachycardia (VT) or ventricular fibrillation (VF) and (ii) non-arrhythmic mortality. Of the 475 included patients, 165 (34.7%) were in the lowest, 220 (46.3%) in the intermediate, and 90 (19.0%) in the highest benefit group. After a median follow-up of 34 months, VT/VF occurred in 3 (1.8%) patients in the lowest, 9 (4.1%) in the intermediate, and 13 (14.4%) in the highest benefit group (P < 0.001). Vice versa, non-arrhythmic death occurred in 32 (19.4%) in the lowest, 32 (14.6%) in the intermediate, and 3 (3.3%) in the highest benefit group (P = 0.002). The predictive power for ICD benefit was comparable between expert multidisciplinary judgement and the MADIT-ICD benefit score: Uno\'s C-statistic 0.69 vs. 0.69 (P = 0.936) for VT/VF and 0.62 vs. 0.60 (P = 0.790) for non-arrhythmic mortality.
Conclusion
The MADIT-ICD benefit score can identify who benefits most from CRT-D and is comparable with multidisciplinary judgement in a CRT expert centre.

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Europace: 30 Mar 2022; epub ahead of print
Dauw J, Martens P, Nijst P, Meekers E, ... Dupont M, Mullens W
Europace: 30 Mar 2022; epub ahead of print | PMID: 35352116
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Abstract

Tricuspid regurgitation after cardiac resynchronization therapy: evolution and prognostic significance.

Stassen J, Galloo X, Hirasawa K, Marsan NA, ... Delgado V, Bax JJ
Aims
Tricuspid regurgitation (TR) is common in patients with heart failure (HF) and is associated with worse outcome. This study investigated the effect of cardiac resynchronization therapy (CRT) on TR severity and long-term outcome.
Methods and results
Tricuspid regurgitation severity was assessed at baseline and 6 months after CRT implantation, using a multiparametric approach. Patients were divided into four groups: (i) no or mild TR without progression; (ii) no or mild TR with progression to significant (moderate-severe) TR; (iii) significant TR with improvement to no or mild TR; and (iv) significant TR without improvement. The primary endpoint was all-cause mortality. A total of 852 patients (mean age 65 ± 11 years, 77% male) were included. At baseline, 184 (22%) patients had significant TR, with 75 (41%) showing significant improvement at 6-month follow-up. After a median follow-up of 92 (50-137) months, 494 (58%) patients died. Patients with significant TR showing improvement at follow-up had better outcomes than those showing no improvement (P = 0.016). On multivariable analysis, no or mild TR progressing to significant TR [hazard ratio (HR) 1.745; 95% confidence interval (CI): 1.287-2.366; P < 0.001] and significant TR without improvement (HR 1.572; 95% CI: 1.198-2.063; P = 0.001) were independently associated with all-cause mortality, whereas significant TR with improvement at follow-up was not (HR: 1.153; 95% CI: 0.814-1.633; P = 0.424).
Conclusion
Improvement of significant TR after CRT is observed in a substantial proportion of patients, highlighting the potential benefit of CRT for patients with HF having significant TR. Significant TR at 6 months after CRT is independently associated with increased long-term mortality.

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Europace: 28 Mar 2022; epub ahead of print
Stassen J, Galloo X, Hirasawa K, Marsan NA, ... Delgado V, Bax JJ
Europace: 28 Mar 2022; epub ahead of print | PMID: 35348656
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Abstract

Endomysial fibrosis, rather than overall connective tissue content, is the main determinant of conduction disturbances in human atrial fibrillation.

Maesen B, Verheule S, Zeemering S, La Meir M, ... Dhein S, Schotten U
Aims
Although in persistent atrial fibrillation (AF) a complex AF substrate characterized by a high incidence of conduction block has been reported, relatively little is known about AF complexity in paroxysmal AF (pAF). Also, the relative contribution of various aspects of structural alterations to conduction disturbances is not clear. In particular, the contribution of endomysial fibrosis to conduction disturbances during progression of AF has not been studied yet.
Methods and results
During cardiac surgery, epicardial high-density mapping was performed in patients with acutely induced (aAF, n = 11), pAF (n = 12), and longstanding persistent AF (persAF, n = 9) on the right atrial (RA) wall, the posterior left atrial wall (pLA) and the LA appendage (LAA). In RA appendages, overall and endomysial (myocyte-to-myocyte distances) fibrosis and connexin 43 (Cx43) distribution were quantified. Unipolar AF electrogram analysis showed a more complex pattern with a larger number of narrower waves, more breakthroughs and a higher fractionation index (FI) in persAF compared with aAF and pAF, with no differences between aAF and pAF. The FI was consistently higher at the pLA compared with the RA. Structurally, Cx43 lateralization increased with AF progression (aAF = 7.5 ± 8.9%, pAF = 24.7 ± 11.1%, persAF = 35.1 ± 11.4%, P < 0.001). Endomysial but not overall fibrosis correlated with AF complexity (r = 0.57, P = 0.001; r = 0.23, P = 0.20; respectively).
Conclusions
Atrial fibrillation complexity is highly variable in patients with pAF, but not significantly higher than in patients with acutely induced AF, while in patients with persistent AF complexity is higher. Among the structural alterations studied, endomysial fibrosis, but not overall fibrosis, is the strongest determinant of AF complexity.

© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.

Europace: 28 Mar 2022; epub ahead of print
Maesen B, Verheule S, Zeemering S, La Meir M, ... Dhein S, Schotten U
Europace: 28 Mar 2022; epub ahead of print | PMID: 35348667
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Abstract

Management of conduction disorders after transcatheter aortic valve implantation: results of the EHRA survey.

Badertscher P, Knecht S, Zeljković I, Sticherling C, ... Kühne M, Boveda S
Conduction disorders such as left bundle branch block (LBBB) are common after transcatheter aortic valve implantation (TAVI). Consensus regarding a reasonable strategy to manage conduction disturbances after TAVI has been elusive. The European Heart Rhythm Association (EHRA) conducted a survey to capture contemporary clinical practice for conduction disorders after TAVI. A 25-item online questionnaire was developed and distributed among the EHRA electrophysiology (EP) research network centres. Of 117 respondents, 44% were affiliated with university hospitals. A standardized management protocol for advanced conduction disorders such as LBBB or atrioventricular block (AVB) after TAVI was available in 63% of participating centres. Telemetry after TAVI was chosen as the most frequent management strategy for patients with new-onset or pre-existing LBBB (79% and 70%, respectively). Duration of telemetry in patients with new-onset LBBB varied, with a 48-h period being the most frequently chosen, but almost half monitoring continued for at least 72 h. Similarly, in patients undergoing EP study due to new-onset LBBB, the HV interval cut-off point leading to pacemaker implantation was heterogeneous among European centres, although an HV >75 ms threshold was the most common. Conduction system pacing was chosen as a preferred approach by 3.7% of respondents for patients with LBBB and normal left ventricular ejection fraction (LVEF), and by 5.6% for patients with LBBB and reduced LVEF. This survey suggests some heterogenity in the management of conduction disorders after TAVI across European centres. The risk stratification strategies vary substantially. Conduction system pacing in patients with LBBB after TAVI is still underused.

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Europace: 26 Mar 2022; epub ahead of print
Badertscher P, Knecht S, Zeljković I, Sticherling C, ... Kühne M, Boveda S
Europace: 26 Mar 2022; epub ahead of print | PMID: 35348646
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Abstract

Performance-based risk-sharing arrangements for devices and procedures in cardiac electrophysiology: an innovative perspective.

Boriani G, Vitolo M, Svennberg E, Casado-Arroyo R, Merino JL, Leclercq C
There is an increasing pressure on demonstrating the value of medical interventions and medical technologies resulting in the proposal of new approaches for implementation in the daily practice of innovative treatments that might carry a substantial cost. While originally mainly adopted by pharmaceutical companies, in recent years medical technology companies have initiated novel value-based arrangements for using medical devices, in the form of \'outcomes-based contracts\', \'performance-based contracts\', or \'risk-sharing agreements\'. These are all characterized by linking coverage, reimbursement, or payment for the innovative treatment to the attainment of pre-specified clinical outcomes. Risk-sharing agreements have been promoted also in the field of electrophysiology and offer the possibility to demonstrate the value of specific innovative technologies proposed in this rapidly advancing field, while relieving hospitals from taking on the whole financial risk themselves. Physicians deeply involved in the field of devices and technologies for arrhythmia management and invasive electrophysiology need to be prepared for involvement as stakeholders. This may imply engagement in the evaluation of risk-sharing agreements and specifically, in the process of assessment of technology performances or patient outcomes. Scientific Associations may have an important role in promoting the basis for value-based assessments, in promoting educational initiatives to help assess the determinants of the learning curve for innovative treatments, and in promoting large-scale registries for a precise assessment of patient outcomes and of specific technologies\' performance.

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Europace: 24 Mar 2022; epub ahead of print
Boriani G, Vitolo M, Svennberg E, Casado-Arroyo R, Merino JL, Leclercq C
Europace: 24 Mar 2022; epub ahead of print | PMID: 35531864
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Abstract

Assessment and mitigation of bleeding risk in atrial fibrillation and venous thromboembolism: A Position Paper from the ESC Working Group on Thrombosis, in collaboration with the European Heart Rhythm Association, the Association for Acute CardioVascular Care and the Asia-Pacific Heart Rhythm Society.

Gorog DA, Gue YX, Chao TF, Fauchier L, ... Vilahur G, Lip GYH
Whilst there is a clear clinical benefit of oral anticoagulation (OAC) in patients with atrial fibrillation (AF) and venous thromboembolism (VTE) in reducing the risks of thromboembolism, major bleeding events (especially intracranial bleeds) may still occur and be devastating. The decision to initiate and continue anticoagulation is often based on a careful assessment of both the thromboembolism and bleeding risk. The more common and validated bleeding risk factors have been used to formulate bleeding risk stratification scores, but thromboembolism and bleeding risk factors often overlap. Also, many factors that increase bleeding risk are transient and modifiable, such as variable international normalized ratio values, surgical procedures, vascular procedures, or drug-drug and food-drug interactions. Bleeding risk is also not a static \'one off\' assessment based on baseline factors but is dynamic, being influenced by ageing, incident comorbidities, and drug therapies. In this Consensus Document, we comprehensively review the published evidence and propose a consensus on bleeding risk assessments in patients with AF and VTE, with the view to summarizing \'best practice\' when approaching antithrombotic therapy in these patients. We address the epidemiology and size of the problem of bleeding risk in AF and VTE, review established bleeding risk factors, and summarize definitions of bleeding. Patient values and preferences, balancing the risk of bleeding against thromboembolism are reviewed, and the prognostic implications of bleeding are discussed. We propose consensus statements that may help to define evidence gaps and assist in everyday clinical practice.

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Europace: 22 Mar 2022; epub ahead of print
Gorog DA, Gue YX, Chao TF, Fauchier L, ... Vilahur G, Lip GYH
Europace: 22 Mar 2022; epub ahead of print | PMID: 35323922
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Abstract

Clinical impact of Bachmann\'s bundle pacing defined by electrocardiographic criteria on atrial arrhythmia outcomes.

Infeld M, Nicoli CD, Meagher S, Tompkins BJ, ... Meyer M, Lustgarten DL
Aims
Evaluate whether Bachmann\'s bundle pacing (BBp) defined by electrocardiographic (ECG) criteria is associated with less atrial fibrillation/tachycardia (AF/AT) compared with anatomically defined right atrial septal pacing (RASp) and right atrial appendage pacing (RAAp).
Methods and results
This is a retrospective study comparing BBp with non-specific RASp and RAAp on new incidence, burden, and recurrence of AF/AT. We included patients who underwent atrial lead placement between 2006 and 2019 and received > 20% atrial pacing. BBp was defined by paced P-wave morphology and fluoroscopic lead position. Compared with RASp (n = 107) and RAAp (n = 108), AF/AT burden was lower in the BBp (n = 134) group by repeated measures ANOVA (P < 0.001). Over 2-year follow-up, AF/AT burden increased in the RASp (P < 0.01) and RAAp (P < 0.01) groups but did not significantly change in the BBp group (P = 0.91). Atrial arrhythmia burden was lower in the BBp group than the RASp and RAAp groups at 12-15, 18-21, and 24-27 months (P < 0.05) after pacemaker placement. Risk of AF/AT recurrence was lower in BBp than RASp (HR 0.43; P < 0.01) and RAAp patients (HR 0.29, P < 0.01). Risk of de novo AF/AT was also lower in BBp than in RASp (OR 0.12; P < 0.01) and RAAp patients (OR 0.20, P < 0.01).
Conclusion
Bachmann\'s bundle pacing defined using P-wave criteria was associated with decreased atrial arrhythmia burden, recurrence, and de novo incidence compared with right atrial septal pacing and right atrial appendage pacing.

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Europace: 19 Mar 2022; epub ahead of print
Infeld M, Nicoli CD, Meagher S, Tompkins BJ, ... Meyer M, Lustgarten DL
Europace: 19 Mar 2022; epub ahead of print | PMID: 35304608
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Abstract

Comparison of various late gadolinium enhancement magnetic resonance imaging methods with high-definition voltage and activation mapping for detection of atrial cardiomyopathy.

Eichenlaub M, Mueller-Edenborn B, Minners J, Figueras I Ventura RM, ... Arentz T, Jadidi A
Aims
Atrial cardiomyopathy (ACM) is associated with increased arrhythmia recurrence rates after pulmonary vein isolation (PVI). We compare the most common left atrial (LA) late gadolinium enhancement magnetic resonance imaging (LGE-MRI)-methods [Utah-method and image intensity ratio (IIR)-methods] and endocardial voltage mapping for ACM-detection and outcome prediction after PVI for atrial fibrillation (AF).
Methods and results
In this prospective observational study, 37 ablation-naive patients (66 ± 9 years, 84% male) with persistent AF underwent LA-LGE-MRI and high-definition voltage and activation mapping (2129 ± 484 sites) in sinus rhythm prior to PVI. The MRI-post-processing-analyses were performed by two independent expert laboratories. Arrhythmia recurrence was recorded within 12 months following PVI. The global ACM-extent was highly variable: median LA low-voltage substrate (LA-LVS) was 12.9% at <1.0 mV and 2.7% at <0.5 mV; median LA-LGE-extent using the Utah-method was 18.3% and 0.03-93.1% using the IIR-methods. The LA activation time was significantly correlated with LA-LVS (r = 0.76 at <0.5 mV and r = 0.82 at <1.0 mV, both P < 0.0001), but not with LA-LGE-extent. The highest regional matching between LA-LVS <0.5 mV and LA-LGE was found for the anterior wall in 57% of patients using the Utah-method and in 59% using IIR 1.20. The corresponding values for the posterior wall were 19% and 38%, respectively. Arrhythmia recurrence occurred in 15(41%) patients. Freedom from arrhythmia was significantly lower in those with LA-LVS ≥2 cm2 at 0.5 mV but not in those with LGE ≥20% (Utah-stages III and IV): 43% vs. 81%, P = 0.009 and 50% vs. 67%, P = 0.338, respectively.
Conclusion
Comparison of the most common LA-LGE-MRI methods and endocardial voltage mapping revealed large discrepancies in global and regional ACM-extent.

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Europace: 16 Mar 2022; epub ahead of print
Eichenlaub M, Mueller-Edenborn B, Minners J, Figueras I Ventura RM, ... Arentz T, Jadidi A
Europace: 16 Mar 2022; epub ahead of print | PMID: 35298612
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Abstract

Incidence and predictors of sudden cardiac death in arrhythmogenic right ventricular cardiomyopathy: a pooled analysis.

Agbaedeng TA, Roberts KA, Colley L, Noubiap JJ, Oxborough D
Aims
Arrhythmogenic right ventricular cardiomyopathy (ARVC), an inherited heart muscle abnormality, is a major cause of sudden cardiac death (SCD). However, the burden of SCD and risk factors in ARVC are not clearly described. Thus, we estimated the rates and predictors of SCD in ARVC in a meta-analysis.
Methods and results
PubMed, Embase, and Web of Science were searched through 7 April 2021. Prospective studies reporting SCD from ARVC cohorts were included. Data were independently extracted by two reviewers and pooled in a random-effects meta-analysis. Fifty-two studies (n = 5485 patients) with moderate-to-low risk of bias were included. The pooled annualized rates of SCD were 0.65 per 1000 [95% confidence interval 0.00-6.43, I2 0.00%] in those with an implantable cardioverter-defibrillator (ICD) and 7.21 (2.38-13.79, I2 0.0%) in non-ICD cohorts: 7.14 in probands and 8.44 for 2010 Task Force Criteria (TFC). Multivariable predictors of life-threatening arrhythmic events including SCD were: age at presentation [adjusted hazard ratio 0.98 (0.97-0.99)], male sex [2.08 (1.29-3.36)], right ventricular (RV) dysfunction [6.99 (2.17-22.49)], QRS fragmentation [6.55 (3.33-12.90)], T-wave inversion [1.12 (1.02-1.24)], syncope at presentation [2.83 (2.40-4.08)], previous non-sustained ventricular tachyarrhythmia [2.53 (1.44-4.45)], and the TFC score [1.96 (1.02-3.76)], (P < 0.05). Predictors of appropriate ICD therapy were RV dysfunction, syncope, and inducible ventricular arrhythmia (P < 0.01).
Conclusion
This meta-analysis demonstrates a high burden of SCD in ARVC patients, especially among probands and ARVC defined by the modified TFC. Better strategies are required to improve patient management and prevent SCD in ARVC. PROSPERO ID: CRD42020211761.

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Europace: 16 Mar 2022; epub ahead of print
Agbaedeng TA, Roberts KA, Colley L, Noubiap JJ, Oxborough D
Europace: 16 Mar 2022; epub ahead of print | PMID: 35298614
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Abstract

Epicardial fat and atrial fibrillation: the perils of atrial failure.

Poggi AL, Gaborit B, Schindler TH, Liberale L, Montecucco F, Carbone F
Obesity is a heterogeneous condition, characterized by different phenotypes and for which the classical assessment with body mass index may underestimate the real impact on cardiovascular (CV) disease burden. An epidemiological link between obesity and atrial fibrillation (AF) has been clearly demonstrated and becomes even more tight when ectopic (i.e. epicardial) fat deposition is considered. Due to anatomical and functional features, a tight paracrine cross-talk exists between epicardial adipose tissue (EAT) and myocardium, including the left atrium (LA). Alongside-and even without-mechanical atrial stretch, the dysfunctional EAT may determine a pro-inflammatory environment in the surrounding myocardial tissue. This evidence has provided a new intriguing pathophysiological link with AF, which in turn is no longer considered a single entity but rather the final stage of atrial remodelling. This maladaptive process would indeed include structural, electric, and autonomic derangement that ultimately leads to overt disease. Here, we update how dysfunctional EAT would orchestrate LA remodelling. Maladaptive changes sustained by dysfunctional EAT are driven by a pro-inflammatory and pro-fibrotic secretome that alters the sinoatrial microenvironment. Structural (e.g. fibro-fatty infiltration) and cellular (e.g. mitochondrial uncoupling, sarcoplasmic reticulum fragmentation, and cellular protein quantity/localization) changes then determine an electrophysiological remodelling that also involves the autonomic nervous system. Finally, we summarize how EAT dysfunction may fit with the standard guidelines for AF. Lastly, we focus on the potential benefit of weight loss and different classes of CV drugs on EAT dysfunction, LA remodelling, and ultimately AF onset and recurrence.

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Europace: 10 Mar 2022; epub ahead of print
Poggi AL, Gaborit B, Schindler TH, Liberale L, Montecucco F, Carbone F
Europace: 10 Mar 2022; epub ahead of print | PMID: 35274140
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Abstract

Watchman FLX vs. Watchman 2.5 in a Dual-Center Left Atrial Appendage Closure Cohort: the WATCH-DUAL study.

Galea R, Mahmoudi K, Gräni C, Elhadad S, ... Amabile N, Räber L
Aims
No studies have compared Watchman 2.5 (W2.5) with Watchman FLX (FLX) devices to date. We aimed at comparing the FLX with W2.5 devices with respect to clinical outcomes, left atrial appendage (LAA) sealing properties and device-related thrombus (DRT).
Methods and results
All consecutive left atrial appendage closure (LAAC) procedures performed at two European centres between November 2017 and February 2021 were included. Procedure-related complications and net adverse cardiovascular events (NACE) at 6 months after LAAC were recorded. At 45-day computed tomography (CT) follow-up, intra- (IDL) and peri- (PDL) device leak, residual patent neck area (RPNA), and DRT were assessed by a Corelab. Out of 144 LAAC consecutive procedures, 71 and 73 interventions were performed using W2.5 and FLX devices, respectively. There were no differences in terms of procedure-related complications (4.2% vs. 2.7%, P = 0.626). At 45-day CT, the FLX was associated with lower frequency of IDL [21.3% vs. 40.0%; P = 0.032; odds ratio (OR): 0.375; 95% confidence interval (CI): 0.160-0.876; P = 0.024], similar rate of PDL (29.5% vs. 42.0%; P = 0.170), and smaller RPNA [6 (0-36) vs. 40 (6-115) mm2; P = 0.001; OR: 0.240; 95% CI: 0.100-0.577; P = 0.001] compared with the W2.5 group. At 45 days, rate of DRT as detected by CT and/or transoesophageal echocardiography (TOE), was higher with W2.5 (6.0% vs. 0%, P = 0.045). At 6-month follow-up, NACE did not differ between groups.
Conclusions
In this cohort of consecutive LAACs, FLX as compared to W2.5, was associated with similar procedure-related complications and 6-month NACE, but with improved LAA neck coverage, and lower IDL and DRT.

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Europace: 06 Mar 2022; epub ahead of print
Galea R, Mahmoudi K, Gräni C, Elhadad S, ... Amabile N, Räber L
Europace: 06 Mar 2022; epub ahead of print | PMID: 35253840
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Abstract

Epidemiology of cerebral microbleeds and risk of adverse outcomes in atrial fibrillation: a systematic review and meta-analysis.

Corica B, Romiti GF, Raparelli V, Cangemi R, Basili S, Proietti M
Aims
The aim of this study is to perform a systematic review and meta-analysis on the epidemiology of cerebral microbleeds (CMBs) and the risk of intracranial haemorrhage (ICH) and ischaemic stroke (IS) in patients with atrial fibrillation (AF).
Methods and results
PubMed and EMBASE databases were systematically searched from inception to 6 March 2021. All studies reporting the prevalence of CMBs and incidence of ICH and IS in AF patients with and without CMBs were included. Meta-analysis was conducted using random-effect models; odds ratios (ORs), 95% confidence intervals (CIs), and prediction intervals (PIs) were calculated for each outcome. Subgroup analyses were performed according to the number and localization of CMBs. A total of 562 studies were retrieved, with 17 studies finally included in the meta-analysis. Prevalence of CMBs in AF population was estimated at 28.3% (95% CI: 23.8-33.4%). Individuals with CMBs showed a higher risk of ICH (OR: 3.04, 95% CI: 1.83-5.06, 95% PI 1.23-7.49) and IS (OR: 1.78, 95% CI: 1.26-2.49, 95% PI 1.10-2.87). Patients with ≥5 CMBs showed a higher risk of ICH. Metaregression showed how higher of prevalence of diabetes mellitus in AF cohort is associated with higher prevalence of CMBs.
Conclusions
Cerebral microbleeds are common in patients with AF, found in almost one out of four subjects. Cerebral microbleeds were associated with both haemorrhagic and thromboembolic events in AF patients. Moreover, the risk of ICH increased consistently with the burden of CMBs. Cerebral microbleeds may represent an important overlooked risk factor for both ICH and IS in adults with AF.

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Europace: 03 Mar 2022; epub ahead of print
Corica B, Romiti GF, Raparelli V, Cangemi R, Basili S, Proietti M
Europace: 03 Mar 2022; epub ahead of print | PMID: 35244694
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Abstract

Impact of oral anticoagulation on the association between frailty and clinical outcomes in people with atrial fibrillation: nationwide primary care records on treatment analysis.

Wilkinson C, Wu J, Clegg A, Nadarajah R, ... Todd O, Gale CP
Aims
People with atrial fibrillation (AF) frequently live with frailty, which increases the risk of mortality and stroke. This study reports the association between oral anticoagulation (OAC) and outcomes for people with frailty, and whether there is overall net benefit from treatment in people with AF.
Methods and results
Retrospective open cohort electronic records study. Frailty was identified using the electronic frailty index. Primary care electronic health records of 89 996 adults with AF and CHA2DS2-Vasc score of ≥2 were linked with secondary care and mortality data in the Clinical Practice Research Database (CPRD) from 1 January 1998 to 30 November 2018. The primary outcome was a composite of death, stroke, systemic embolism, or major bleeding. Secondary outcomes were stroke, major bleeding, all-cause mortality, transient ischaemic attack, and falls. Of 89 996 participants, 71 256 (79.2%) were living with frailty. The prescription of OAC increased with degree of frailty. For patients not prescribed OAC, rates of the primary outcome increased alongside frailty category. Prescription of OAC was associated with a reduction in the primary outcome for each frailty category [adjusted hazard ratio, 95% confidence interval, no OAC as reference; fit: vitamin K antagonist (VKA) 0.69, 0.64-0.75, direct oral anticoagulant (DOAC) 0.42, 0.33-0.53; mild frailty: VKA 0.52, 0.50-0.54, DOAC 0.57, 0.52-0.63; moderate: VKA 0.54, 0.52-0.56, DOAC 0.57, 0.52-0.63; severe: VKA 0.48, 0.45-0.51, DOAC 0.58, 0.52-0.65], with cumulative incidence function effects greater for DOAC than VKA.
Conclusion
Frailty among people with AF is common. The OAC was associated with a reduction in the primary endpoint across all degrees of frailty.

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Europace: 03 Mar 2022; epub ahead of print
Wilkinson C, Wu J, Clegg A, Nadarajah R, ... Todd O, Gale CP
Europace: 03 Mar 2022; epub ahead of print | PMID: 35244709
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Abstract

Prevalence and clinical significance of isolated low QRS voltages in young athletes.

Zorzi A, Bettella N, Tatangelo M, Del Monte A, ... Pelliccia A, Corrado D
Aims
Low QRS voltages (peak to peak <0.5 mV) in limb leads (LQRSV) on the athlete\'s electrocardiogram (ECG) may reflect an underlying cardiomyopathy, mostly arrhythmogenic cardiomyopathy (ACM) or non-ischaemic left ventricular scar (NILVS). We studied the prevalence and clinical meaning of isolated LQRSV in a large cohort of competitive athletes.
Methods and results
The index group included 2229 Italian competitive athletes [median age 18 years (16-25), 67% males, 97% Caucasian] without major ECG abnormalities at pre-participation screening. Three control groups included Black athletes (N = 1115), general population (N = 1115), and patients with ACM or NILVS (N = 58). Echocardiogram was performed in all athletes with isolated LQRSV and cardiac magnetic resonance (CMR) in those with ventricular arrhythmias or echocardiographic abnormalities. The isolated LQRSV pattern was found in 1.1% index athletes and was associated with increasing age (median age 28 vs. 18 years; P < 0.001), elite status (71% vs. 34%; P < 0.001), body surface area, and body mass index but not with sex, type of sport, and echocardiographic left ventricular mass. The prevalence of isolated LQRSV was 0.2% in Black athletes and 0.3% in young individuals from the general population. Cardiomyopathy patients had a significantly greater prevalence of isolated LQRSV (12%) than index athletes, Black athletes, and general population. Five index athletes with isolated LQSRV and exercise-induced ventricular arrhythmias underwent CMR showing biventricular ACM in 1 and idiopathic NILVS in 1.
Conclusions
Unlike cardiomyopathy patients, the ECG pattern of isolated LQRSV was rarely observed in athletes. This ECG sign should prompt clinical work-up for exclusion of an underlying cardiomyopathy.

© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.

Europace: 03 Mar 2022; epub ahead of print
Zorzi A, Bettella N, Tatangelo M, Del Monte A, ... Pelliccia A, Corrado D
Europace: 03 Mar 2022; epub ahead of print | PMID: 35243505
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Abstract

Miniseries 1-Part I: the Development of the atrioventricular conduction axis.

Hikspoors JPJM, Macías Y, Tretter JT, Anderson RH, ... Farré J, Back Sternick E
Despite years of research, many details of the formation of the atrioventricular conduction axis remain uncertain. In this study, we aimed to clarify the situation. We studied three-dimensional reconstructions of serial histological sections and episcopic datasets of human embryos, supplementing these findings with assessment of material housed at the Human Developmental Biological Resource. We also examined serially sectioned human foetal hearts between 10 and 30 weeks of gestation. The conduction axis originates from the primary interventricular ring, which is initially at right angles to the plane of the atrioventricular canal, with which it co-localizes in the lesser curvature of the heart loop. With rightward expansion of the atrioventricular canal, the primary ring bends rightward, encircling the newly forming right atrioventricular junction. Subsequent to remodelling of the outflow tract, part of the primary ring remains localized on the crest of the muscular ventricular septum. By 7 weeks, its atrioventricular part has extended perpendicular to the septal parts. The atrioventricular node is formed at the inferior transition between the ventricular and atrial parts, with the transition itself marking the site of the penetrating atrioventricular bundle. Only subsequent to muscularization of the true second atrial septum does it become possible to recognize the definitive node. The conversion of the developmental arrangement into the definitive situation as seen postnatally requires additional remodelling in the first month of foetal development, concomitant with formation of the inferior pyramidal space and the infero-septal recess of the subaortic outflow tract.

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Europace: 02 Mar 2022; 24:432-442
Hikspoors JPJM, Macías Y, Tretter JT, Anderson RH, ... Farré J, Back Sternick E
Europace: 02 Mar 2022; 24:432-442 | PMID: 34999831
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Abstract

Miniseries 1-Part III: \'Behind the scenes\' in the triangle of Koch.

Tretter JT, Spicer DE, Sánchez-Quintana D, Back Sternick E, Farré J, Anderson RH
Aims
To take full advantage of the knowledge of cardiac anatomy, structures should be considered in their correct attitudinal orientation. Our aim was to discuss the triangle of Koch in an attitudinally appropriate fashion.
Methods and results
We reviewed our material prepared by histological sectioning, along with computed tomographic datasets of human hearts. The triangle of Koch is the right atrial surface of the inferior pyramidal space, being bordered by the tendon of Todaro and the hinge of the septal leaflet of the tricuspid valve, with its base at the inferior cavotricuspid isthmus. The fibro-adipose tissues of the inferior pyramidal space separate the atrial wall from the crest of the muscular interventricular septum, thus producing an atrioventricular muscular sandwich. The overall area is better approached as a pyramid rather than a triangle. The apex of the inferior pyramidal space overlaps the infero-septal recess of the subaortic outflow tract, permitting the atrioventricular conduction axis to transition directly to the crest of the muscular ventricular septum. The compact atrioventricular node is formed at the apex of the pyramid by union of its inferior extensions, which represent the slow pathway, with the septal components formed in the buttress of the atrial septum, thus providing the fast pathway.
Conclusions
To understand its various implications in current cardiological catheter interventions, the triangle of Koch must be considered in conjunction with the inferior pyramidal space and the infero-septal recess. It is better to consider the overall region in terms of a pyramidal area of interest.

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Europace: 02 Mar 2022; 24:455-463
Tretter JT, Spicer DE, Sánchez-Quintana D, Back Sternick E, Farré J, Anderson RH
Europace: 02 Mar 2022; 24:455-463 | PMID: 34999775
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Abstract

Miniseries 1-Part IV: How frequent are fasciculo-ventricular connections in the normal heart?

Macías Y, Tretter JT, Anderson RH, Sánchez-Quintana D, ... Farré J, Back Sternick E
Aims
Seeking to account for accessory atrioventricular conduction potentially leading to ventricular pre-excitation, Mahaim in the mid-20th century had described pathways between the atrioventricular conduction axis and the muscular ventricular septum. We aimed to look for such \'paraspecific\' connections in adult human hearts.
Methods and results
We serially sectioned 21 hearts, covering the triangle of Koch and the aortic root, and assessing the atrioventricular node, the penetration of the conduction axis, and the bundle branches in our search for fasciculo-ventricular connections. We also calculated the length of the non-branching bundle, and if present the origin of the fasciculo-ventricular connections. The non-branching bundle was 3.6 ± 1.7 mmin length, varying from 1.7 mm to 7.2 mm. Fasciculo-ventricular connections were found in more than half of the hearts, making direct contact with the muscular septum at an average of 3.5 ± 1.7 mm from the origin of the left bundle branch, with the site of origin varying from 1.1 mm to 5.5 mm from the first fascicle of the left bundle branch. In three hearts, additional fasciculo-fascicular connections were observed in the left bundle branch. Two loops were small, but one loop extended over 9.5 mm.
Conclusion
We endorse the finding of Mahaim that fasciculo-ventricular pathways exist in most human hearts. We presume the identified connections had the capability of producing ventricular pre-excitation. More studies are needed to determine the potential clinical manifestations.

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Europace: 02 Mar 2022; 24:464-472
Macías Y, Tretter JT, Anderson RH, Sánchez-Quintana D, ... Farré J, Back Sternick E
Europace: 02 Mar 2022; 24:464-472 | PMID: 34999781
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Abstract

Miniseries 1-Part II: the comparative anatomy of the atrioventricular conduction axis.

Macías Y, de Almeida MC, Tretter JT, Anderson RH, ... Farré J, Back Sternick E
Aims
The arrangement of the conduction axis is markedly different in various mammalian species. Knowledge of such variation may serve to question the validity of using animals as prospective models for design of systems for clinical use.
Methods and results
We compared the arrangement of the atrioventricular conduction axis in human, murine, canine, porcine, and bovine hearts, examining serially sectioned datasets from 20 human, 16 murine, 3 porcine, 5 canine, and 1 bovine hearts. We also analysed computed tomographic datasets obtained from bovines and one human heart. Unlike the situation in the human heart, there is no formation of an atrioventricular fibrous membranous septum in the murine, canine, porcine, nor bovine hearts. Canine, porcine, and bovine hearts also lack an infero-septal recess, when defined as a fibrous plate supporting the buttress of the atrial septum. In these species, half of the non-coronary leaflet is directly opposed to the ventricular septal surface.
Conclusion
There is a long right-sided non-branching component of the axis, which skirts the attachment of the non-coronary sinus of the aortic root. In the bovine heart, moreover, the left bundle branch usually extends intramyocardially as a solitary tape before surfacing and ramifying on the left ventricular septal surface. The difference in the atrioventricular conduction axis between species may influence the anatomical substrates for atrioventricular re-entry tachycardia, as well as providing inferences for assessing the risks of transcatheter implantation of the aortic valve. Further studies are now needed to assess these possibilities.

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Europace: 02 Mar 2022; 24:443-454
Macías Y, de Almeida MC, Tretter JT, Anderson RH, ... Farré J, Back Sternick E
Europace: 02 Mar 2022; 24:443-454 | PMID: 34999788
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Abstract

Loss-of-function mutations in cardiac ryanodine receptor channel cause various types of arrhythmias including long QT syndrome.

Hirose S, Murayama T, Tetsuo N, Hoshiai M, ... Kurebayashi N, Ohno S
Aims
Gain-of-function mutations in RYR2, encoding the cardiac ryanodine receptor channel (RyR2), cause catecholaminergic polymorphic ventricular tachycardia (CPVT). Whereas, genotype-phenotype correlations of loss-of-function mutations remains unknown, due to a small number of analysed mutations. In this study, we aimed to investigate their genotype-phenotype correlations in patients with loss-of-function RYR2 mutations.
Methods and results
We performed targeted gene sequencing for 710 probands younger than 16-year-old with inherited primary arrhythmia syndromes (IPAS). RYR2 mutations were identified in 63 probands, and 3 probands displayed clinical features different from CPVT. A proband with p.E4146D developed ventricular fibrillation (VF) and QT prolongation whereas that with p.S4168P showed QT prolongation and bradycardia. Another proband with p.S4938F showed short-coupled variant of torsade de pointes (scTdP). To evaluate the functional alterations in these three mutant RyR2s and p.K4594Q previously reported in a long QT syndrome (LQTS), we measured Ca2+ signals in HEK293 cells and HL-1 cardiomyocytes as well as Ca2+-dependent [3H]ryanodine binding. All mutant RyR2s demonstrated a reduced Ca2+ release, an increased endoplasmic reticulum Ca2+, and a reduced [3H]ryanodine binding, indicating loss-of-functions. In HL-1 cells, the exogenous expression of S4168P and K4594Q reduced amplitude of Ca2+ transients without inducing Ca2+ waves, whereas that of E4146D and S4938F evoked frequent localized Ca2+ waves.
Conclusion
Loss-of-function RYR2 mutations may be implicated in various types of arrhythmias including LQTS, VF, and scTdP, depending on alteration of the channel activity. Search of RYR2 mutations in IPAS patients clinically different from CPVT will be a useful strategy to effectively discover loss-of-function RYR2 mutations.

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Europace: 01 Mar 2022; 24:497-510
Hirose S, Murayama T, Tetsuo N, Hoshiai M, ... Kurebayashi N, Ohno S
Europace: 01 Mar 2022; 24:497-510 | PMID: 34661651
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Abstract

Safety of very high-power short-duration radiofrequency ablation for pulmonary vein isolation: a two-centre report with emphasis on silent oesophageal injury.

Halbfass P, Wielandts JY, Knecht S, Le Polain de Waroux JB, ... Duytschaever M, Deneke T
Aims
Very high-power short-duration (vHPSD) via temperature-controlled ablation (TCA) is a new modality to perform radiofrequency pulmonary vein isolation (PVI), conceivably at the cost of a narrower safety margin towards the oesophagus. In this two-centre trial, we aimed to determine the safety of vHPSD-based PVI with specific emphasis on silent oesophageal injury.
Methods and results
Ninety consecutive patients with atrial fibrillation (AF) underwent vHPSD-PVI (90 W, 3-4 s, TCA) using the QDOT MICRO catheter, in conjunction with the nGEN (Bad Neustadt, n = 45) or nMARQ generator (Bruges, n = 45). All patients underwent post-ablation oesophageal endoscopy. Procedural parameters and complications were recorded. A subgroup of 21 patients from Bad Neustadt underwent cerebral magnetic resonance imaging (cMRI) to detect silent cerebral events (SCEs). Mean age was 67 ± 9 years, 59% patients were male, and 66% patients had paroxysmal AF. Pulmonary vein isolation was obtained in all cases after 96 ± 29 min. No steam pop, cardiac tamponade, stroke, or fistula was reported. None of the 90 patients demonstrated oesophageal ulceration (0%). Charring was not observed in the nMARQ cohort (0% vs. 11% in the nGEN group). In 5 out of 21 patients (24%), cMRI demonstrated SCE (exclusively nGEN cohort).
Conclusion
Temperature-controlled vHPSD catheter ablation allows straightforward PVI without evidence of oesophageal ulcerations or symptomatic complications. Catheter tip charring and silent cerebral lesions when using the nGEN generator have led to further modification.

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Europace: 01 Mar 2022; 24:400-405
Halbfass P, Wielandts JY, Knecht S, Le Polain de Waroux JB, ... Duytschaever M, Deneke T
Europace: 01 Mar 2022; 24:400-405 | PMID: 34757432
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Abstract

Rate control drugs differ in the prevention of progression of atrial fibrillation.

Koldenhof T, Wijtvliet PEPJ, Pluymaekers NAHA, Rienstra M, ... Crijns HJGM, Tieleman RG
Aims
We hypothesize that in patients with paroxysmal atrial fibrillation (AF), verapamil is associated with lower AF progression compared to beta blockers or no rate control.
Methods and results
In this pre-specified post hoc analysis of the RACE 4 randomized trial, the effect of rate control medication on AF progression in paroxysmal AF was analysed. Patients using Vaughan-Williams Class I or III antiarrhythmic drugs were excluded. The primary outcome was a composite of first electrical cardioversion (ECV), chemical cardioversion (CCV), or atrial ablation. Event rates are displayed using Kaplan-Meier curves and multivariable Cox regression analyses are used to adjust for baseline differences. Out of 666 patients with paroxysmal AF, 47 used verapamil, 383 used beta blockers, and 236 did not use rate control drugs. The verapamil group was significantly younger than the beta blocker group and contained more men than the no rate control group. Over a mean follow-up of 37 months, the primary outcome occurred in 17% in the verapamil group, 33% in the beta blocker group, and 33% in the no rate control group (P = 0.038). After adjusting for baseline characteristics, patients using verapamil have a significantly lower chance of receiving ECV, CCV, or atrial ablation compared to patients using beta blockers [hazard ratio (HR) 0.40, 95% confidence interval (CI) 0.19-0.83] and no rate control (HR 0.64, 95% CI 0.44-0.93).
Conclusion
In patients with newly diagnosed paroxysmal AF, verapamil was associated with less AF progression, as compared to beta blockers and no rate control.

© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.

Europace: 01 Mar 2022; 24:384-389
Koldenhof T, Wijtvliet PEPJ, Pluymaekers NAHA, Rienstra M, ... Crijns HJGM, Tieleman RG
Europace: 01 Mar 2022; 24:384-389 | PMID: 34414430
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Abstract

Docosahexaenoic acid normalizes QT interval in long QT type 2 transgenic rabbit models in a genotype-specific fashion.

Castiglione A, Hornyik T, Wülfers EM, Giammarino L, ... Baczkó I, Odening KE
Aim
Long QT syndrome (LQTS) is a cardiac channelopathy predisposing to ventricular arrhythmias and sudden cardiac death. Since current therapies often fail to prevent arrhythmic events in certain LQTS subtypes, new therapeutic strategies are needed. Docosahexaenoic acid (DHA) is a polyunsaturated fatty acid, which enhances the repolarizing IKs current.
Methods and results
We investigated the effects of DHA in wild type (WT) and transgenic long QT Type 1 (LQT1; loss of IKs), LQT2 (loss of IKr), LQT5 (reduction of IKs), and LQT2-5 (loss of IKr and reduction of IKs) rabbits. In vivo ECGs were recorded at baseline and after 10 µM/kg DHA to assess changes in heart-rate corrected QT (QTc) and short-term variability of QT (STVQT). Ex vivo monophasic action potentials were recorded in Langendorff-perfused rabbit hearts, and action potential duration (APD75) and triangulation were assessed. Docosahexaenoic acid significantly shortened QTc in vivo only in WT and LQT2 rabbits, in which both α- and β-subunits of IKs-conducting channels are functionally intact. In LQT2, this led to a normalization of QTc and of its short-term variability. Docosahexaenoic acid had no effect on QTc in LQT1, LQT5, and LQT2-5. Similarly, ex vivo, DHA shortened APD75 in WT and normalized it in LQT2, and additionally decreased AP triangulation in LQT2.
Conclusions
Docosahexaenoic acid exerts a genotype-specific beneficial shortening/normalizing effect on QTc and APD75 and reduces pro-arrhythmia markers STVQT and AP triangulation through activation of IKs in LQT2 rabbits but has no effects if either α- or β-subunits to IKs are functionally impaired. Docosahexaenoic acid could represent a new genotype-specific therapy in LQT2.

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Europace: 01 Mar 2022; 24:511-522
Castiglione A, Hornyik T, Wülfers EM, Giammarino L, ... Baczkó I, Odening KE
Europace: 01 Mar 2022; 24:511-522 | PMID: 34601592
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Abstract

Antibiotic prophylaxis based on individual infective risk stratification in cardiac implantable electronic device: the PRACTICE study.

Malagù M, Vitali F, Brieda A, Cimaglia P, ... Rapezzi C, Bertini M
Aims
In patients undergoing cardiac implantable electronic device (CIED) intervention, routine pre-procedure antibiotic prophylaxis is recommended. A more powerful antibiotic protocol has been suggested in patients at high risk of infection. Stratification of individual infective risk could guide the prophylaxis before CIED procedure.
Methods and results
Patients undergoing CIED surgery were stratified according to the Shariff score in low and high infective risk. Patients in the \'low-risk\' group were treated with only two antibiotic administrations while patients in the \'high-risk\' group were treated with a prolonged 9-day protocol, according to renal function and allergies. We followed-up patients for 250 days with clinical outpatient visit and electronic control of the CIED. As primary endpoint, we evaluated CIED-related infections. A total of 937 consecutive patients were enrolled, of whom 735 were stratified in the \'low-risk\' group and 202 in the \'high-risk\' group. Despite different risk profiles, CIED-related infection rate at 250 days was similar in the two groups (8/735 in \'low risk\' vs. 4/202 in \'high risk\', P = 0.32). At multivariate analysis, active neoplasia, haematoma, and reintervention were independently associated with CIED-related infection (HR 5.54, 10.77, and 12.15, respectively).
Conclusion
In a large cohort of patients undergoing CIED procedure, an antibiotic prophylaxis based on individual stratification of infective risk resulted in similar rate of infection between groups at high and low risk of CIED-related infection.

© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.

Europace: 01 Mar 2022; 24:413-420
Malagù M, Vitali F, Brieda A, Cimaglia P, ... Rapezzi C, Bertini M
Europace: 01 Mar 2022; 24:413-420 | PMID: 34487163
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Abstract

The use of remote monitoring of cardiac implantable devices during the COVID-19 pandemic: an EHRA physician survey.

Simovic S, Providencia R, Barra S, Kircanski B, ... Anic A, Boveda S
It is unclear to what extent the COVID-19 pandemic has influenced the use of remote monitoring (RM) of cardiac implantable electronic devices (CIEDs). The present physician-based European Heart Rhythm Association (EHRA) survey aimed to assess the influence of the COVID-19 pandemic on RM of CIEDs among EHRA members and how it changed the current practice. The survey comprised 27 questions focusing on RM use before and during the pandemic. Questions focused on the impact of COVID-19 on the frequency of in-office visits, data filtering, reasons for initiating in-person visits, underutilization of RM during COVID-19, and RM reimbursement. A total of 160 participants from 28 countries completed the survey. Compared to the pre-pandemic period, there was a significant increase in the use of RM in patients with pacemakers (PMs) and implantable loop recorders (ILRs) during the COVID-19 pandemic (PM 24.2 vs. 39.9%, P = 0.002; ILRs 61.5 vs. 73.5%, P = 0.028), while there was a trend towards higher utilization of RM for cardiac resynchronization therapy-pacemaker (CRT-P) devices during the pandemic (44.5 vs. 55%, P = 0.063). The use of RM with implantable cardioverter-defibrillators (ICDs) and CRT-defibrillator (CRT-D) did not significantly change during the pandemic (ICD 65.2 vs. 69.6%, P = 0.408; CRT-D 65.2 vs. 68.8%, P = 0.513). The frequency of in-office visits was significantly lower during the pandemic (P < 0.001). Nearly two-thirds of participants (57 out of 87 respondents), established new RM connections for CIEDs implanted before the pandemic with 33.3% (n = 29) delivering RM transmitters to the patient\'s home address, and the remaining 32.1% (n = 28) activating RM connections during an in-office visit. The results of this survey suggest that the crisis caused by COVID-19 has led to a significant increase in the use of RM of CIEDs.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.

Europace: 01 Mar 2022; 24:473-480
Simovic S, Providencia R, Barra S, Kircanski B, ... Anic A, Boveda S
Europace: 01 Mar 2022; 24:473-480 | PMID: 34410364
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Abstract

Current clinical practice in patients with cardiac implantable electronic devices undergoing radiotherapy: a literature review.

Azraai M, D\'Souza D, Lin YH, Nadurata V
Patients with cardiac implantable electronic devices (CIED) undergoing radiotherapy (RT) are more common due to the ageing of the population. With newer CIEDs\' implementing the complementary metal-oxide semiconductor (CMOS) technology which allows the miniaturization of CIED, it is also more susceptible to RT. Effects of RT on CIED ranges from device interference, device operational/memory errors of permanent damage. These malfunctions can cause life-threatening clinical effects. Cumulative dose is not the only component of RT that causes CIED malfunction, as neutron use and dose rate effect also affects CIEDs. The management of this patient cohort in clinical practice is inconsistent due to the lack of a consistent guideline from manufacturers and physician specialty societies. Our review will focus on the current clinical practice and the recently updated guidelines of managing patients with CIED undergoing RT. We aim to simplify the evidence and provide a simple and easy to use guide based on the recent guidelines.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.

Europace: 01 Mar 2022; 24:362-374
Azraai M, D'Souza D, Lin YH, Nadurata V
Europace: 01 Mar 2022; 24:362-374 | PMID: 34516616
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Abstract

Preclinical short QT syndrome models: studying the phenotype and drug-screening.

Fan X, Yang G, Kowitz J, Duru F, ... Zhou X, El-Battrawy I
Cardiovascular diseases are the main cause of sudden cardiac death (SCD) in developed and developing countries. Inherited cardiac channelopathies are linked to 5-10% of SCDs, mainly in the young. Short QT syndrome (SQTS) is a rare inherited channelopathy, which leads to both atrial and ventricular tachyarrhythmias, syncope, and even SCD. International European Society of Cardiology guidelines include as diagnostic criteria: (i) QTc ≤ 340 ms on electrocardiogram, (ii) QTc ≤ 360 ms plus one of the follwing, an affected short QT syndrome pathogenic gene mutation, or family history of SQTS, or aborted cardiac arrest, or family history of cardiac arrest in the young. However, further evaluation of the QTc ranges seems to be required, which might be possible by assembling large short QT cohorts and considering genetic screening of the newly described pathogenic mutations. Since the mechanisms underlying the arrhythmogenesis of SQTS is unclear, optimal therapy for SQTS is still lacking. The disease is rare, unclear genotype-phenotype correlations exist in a bevy of cases and the absence of an international short QT registry limit studies on the pathophysiological mechanisms of arrhythmogenesis and therapy of SQTS. This leads to the necessity of experimental models or platforms for studying SQTS. Here, we focus on reviewing preclinical SQTS models and platforms such as animal models, heterologous expression systems, human-induced pluripotent stem cell-derived cardiomyocyte models and computer models as well as three-dimensional engineered heart tissues. We discuss their usefulness for SQTS studies to examine genotype-phenotype associations, uncover disease mechanisms and test drugs. These models might be helpful for providing novel insights into the exact pathophysiological mechanisms of this channelopathy and may offer opportunities to improve the diagnosis and treatment of patients with SQT syndrome.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.

Europace: 01 Mar 2022; 24:481-493
Fan X, Yang G, Kowitz J, Duru F, ... Zhou X, El-Battrawy I
Europace: 01 Mar 2022; 24:481-493 | PMID: 34516623
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Abstract

Using a smartwatch electrocardiogram to detect abnormalities associated with sudden cardiac arrest in young adults.

Nasarre M, Strik M, Daniel Ramirez F, Buliard S, ... Haïssaguerre M, Bordachar P
Aims 
Smartwatch electrocardiograms (ECGs) could facilitate the detection of sudden cardiac arrest (SCA)-associated abnormalities. We evaluated the feasibility of using smartwatch-derived ECGs for detecting SCA-associated abnormalities in young adults and its agreement with 12-lead ECGs.
Methods and results 
Twelve-lead and Apple Watch ECGs were registered in 155 healthy volunteers and 67 patients aged 18-45 years with diagnosis and ECG signs of long-QT syndrome (n = 10), Brugada syndrome (n = 12), ventricular pre-excitation (n = 19), hypertrophic cardiomyopathy (HCM, n = 13), and arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVC/D, n = 13). Cardiologists separately analysed 12-lead ECGs and the smartwatch ECGs taken from the left wrist (AW-I) and then from chest positions V1, V3, and V6 (AW-4). Compared with AW-I, AW-4 improved the classification of ECGs as \'abnormal\', increasing the sensitivity from 64% to 89% (P < 0.01). Pre-excitation was detected in most cases using AW-I (sensitivity 89%) and in all cases using AW-4 (sensitivity 100%, P = 0.48 compared with AW-I, specificity 100% for both). Brugada was missed using AW-I but was detected in 11/12 patients using AW-4 (sensitivity 92%, specificity 100%, P = 0.003). Long QT was detected in 8/10 cases using AW-I (sensitivity 80%, specificity 100%) and in 9 patients using AW-4 (sensitivity 90%, specificity 100%, P > 0.99). Hypertrophic cardiomyopathy was correctly suspected using AW-I and AW-4 (sensitivity 92% and 85%, specificity 85%, and 100%, P > 0.99). AW-I was mostly (62%) considered normal in ARVC/D whereas AW-4 was useful in suspecting ARVC/D (100% sensitivity, 99% specificity, P = 0.004).
Conclusions 
Detection of SCA-associated ECG abnormalities (pre-excitation, Brugada patterns, long QT, and signs suggestive of HCM and ARVC/D) is possible with an ECG smartwatch.

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Europace: 01 Mar 2022; 24:406-412
Nasarre M, Strik M, Daniel Ramirez F, Buliard S, ... Haïssaguerre M, Bordachar P
Europace: 01 Mar 2022; 24:406-412 | PMID: 34468759
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Abstract

Personalized paroxysmal atrial fibrillation ablation by tailoring ablation index to the left atrial wall thickness: the \'Ablate by-LAW\' single-centre study-a pilot study.

Teres C, Soto-Iglesias D, Penela D, Jáuregui B, ... Ortíz-Pérez JT, Berruezo A
Aims
To determine if adapting the ablation index (AI) to the left atrial wall thickness (LAWT), which is a determinant of lesion transmurality, is feasible, effective, and safe during paroxysmal atrial fibrillation (PAF) ablation.
Methods and results
Consecutive patients referred for PAF first ablation. Left atrial wall thickness three-dimensional maps were obtained from multidetector computed tomography and integrated into the CARTO navigation system. Left atrial wall thickness was categorized into 1 mm layers and AI was titrated to the LAWT. The ablation line was personalized to avoid thicker regions. Primary endpoints were acute efficacy and safety, and freedom from atrial fibrillation (AF) recurrences. Follow-up (FU) was scheduled at 1, 3, 6, and every 6 months thereafter. Ninety patients [60 (67%) male, age 58 ± 13 years] were included. Mean LAWT was 1.25 ± 0.62 mm. Mean AI was 366 ± 26 on the right pulmonary veins with a first-pass isolation in 84 (93%) patients and 380 ± 42 on the left pulmonary veins with first-pass in 87 (97%). Procedure time was 59 min (49-66); radiofrequency (RF) time 14 min (12.5-16); and fluoroscopy time 0.7 min (0.5-1.4). No major complication occurred. Eighty-four out of 90 (93.3%) patients were free of recurrence after a mean FU of 16 ± 4 months.
Conclusion
Personalized AF ablation, adapting the AI to LAWT allowed pulmonary vein isolation with low RF delivery, fluoroscopy, and procedure time while obtaining a high rate of first-pass isolation, in this patient population. Freedom from AF recurrences was as high as in more demanding ablation protocols. A multicentre trial is ongoing to evaluate reproducibility of these results.

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Europace: 01 Mar 2022; 24:390-399
Teres C, Soto-Iglesias D, Penela D, Jáuregui B, ... Ortíz-Pérez JT, Berruezo A
Europace: 01 Mar 2022; 24:390-399 | PMID: 34480548
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Abstract

Characteristics of patients with atrial high rate episodes detected by implanted defibrillator and resynchronization devices.

Miyazawa K, Pastori D, Martin DT, Choucair WK, ... Lip GYH, IMPACT Study Investigators
Aims
Atrial high rate episodes (AHREs) are associated with increased risks of thromboembolism and cardiovascular mortality. However, the clinical characteristics of patients developing AHRE of various durations are not well studied.
Methods and results
This was an ancillary analysis of the multicentre, randomized IMPACT trial. In the present analysis, we classified patients according to the duration of AHRE ≤6 min, >6 min to ≤6 h, >6 to ≤24 h and >24 h, and investigated the association between clinical factors and the development of each duration of AHRE. Of 2718 patients included in the trial, 945 (34.8%) developed AHRE. The incidence rates of each AHRE duration category were 5.4/100, 12.0/100, 6.8/100, and 3.3/100 patient-years, respectively. The incidence rates of AHRE >6 h were significantly higher in patients at high risk of thromboembolism (CHADS2 score ≥3) compared to those at low risk (CHADS2 score 1 or 2). Using Cox regression analysis, age ≥65 years and history of atrial fibrillation (AF) and/or atrial flutter (AFL) were risk factors for AHRE >6 min. In addition, hypertension was associated with AHRE >24 h (hazard ratio 2.13, 95% confidence interval 1.24-3.65, P = 0.006).
Conclusion
Atrial high rate episode >6 min to ≤6 h were most prevalent among all AHRE duration categories. Longer AHREs were more common in patients at risk of thromboembolism. Age and history of AF/AFL were risk factors for AHRE >6 min. Furthermore, hypertension showed a strong impact on the development of AHRE >24 h rather than age.

© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.

Europace: 01 Mar 2022; 24:375-383
Miyazawa K, Pastori D, Martin DT, Choucair WK, ... Lip GYH, IMPACT Study Investigators
Europace: 01 Mar 2022; 24:375-383 | PMID: 34426836
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Abstract

Rate of device-related infections using an antibacterial envelope in patients undergoing cardiac resynchronization therapy reoperations.

Frausing MHJP, Nielsen JC, Johansen JB, Jørgensen OD, ... Olsen T, Kronborg MB
Aims 
Cardiac resynchronization therapy (CRT) reoperations are associated with a particularly high risk of device-related infection (DRI). An antibacterial envelope reduces the occurrence of DRIs in a broad population of moderate-tohigh-risk patients. To investigate the efficacy of an antibacterial envelope in a very high-risk population of patients undergoing CRT reoperation.
Methods and results
In this Danish two-centre, observational cohort study, we included consecutive patients who underwent a CRT pacemaker- or defibrillator reoperation procedure between January 2008 and November 2019. We obtained data from the Danish Pacemaker and ICD Register and through systematic medical chart review. Follow-up was restricted to 2 years. A total of 1943 patients were included in the study of which 736 (38%) received an envelope. Envelope patients had more independent risk factors for infection than non-envelope patients. Sixty-seven (3.4%) patients met the primary endpoint of DRI requiring device system extraction; 50 in the non-envelope group and 17 in the envelope group [4.1% vs. 2.3%, adjusted hazard ratio (HR) 0.52, 95% confidence interval (CI) 0.30-0.90; P = 0.021]. This difference persisted in propensity score analysis (HR 0.51, 95% CI 0.29-0.90; P = 0.019).
Conclusion 
Use of an antibacterial envelope was associated with a clinically and statistically significant reduction in DRIs in patients undergoing CRT reoperations. Our results were comparable to those recently reported from a large randomized controlled trial, which is suggestive of a proportional effect of the envelope even in very high-risk patients.

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Europace: 01 Mar 2022; 24:421-429
Frausing MHJP, Nielsen JC, Johansen JB, Jørgensen OD, ... Olsen T, Kronborg MB
Europace: 01 Mar 2022; 24:421-429 | PMID: 34431989
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Abstract

Electrical markers and arrhythmic risk associated with myocardial fibrosis in mitral valve prolapse.

Chivulescu M, Aabel EW, Gjertsen E, Hopp E, ... Dejgaard LA, Haugaa KH
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.

Europace: 27 Feb 2022; epub ahead of print
Chivulescu M, Aabel EW, Gjertsen E, Hopp E, ... Dejgaard LA, Haugaa KH
Europace: 27 Feb 2022; epub ahead of print | PMID: 35226070
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Abstract

Budget impact analysis of a machine learning algorithm to predict high risk of atrial fibrillation among primary care patients.

Szymanski T, Ashton R, Sekelj S, Petrungaro B, ... Hill NR, Farooqui U
Aims
We investigated whether the use of an atrial fibrillation (AF) risk prediction algorithm could improve AF detection compared with opportunistic screening in primary care and assessed the associated budget impact.
Methods and results
Eligible patients were registered with a general practice in UK, aged 65 years or older in 2018/19, and had complete data for weight, height, body mass index, and systolic and diastolic blood pressure recorded within 1 year. Three screening scenarios were assessed: (i) opportunistic screening and diagnosis (standard care); (ii) standard care replaced by the use of the algorithm; and (iii) combined use of standard care and the algorithm. The analysis considered a 3-year time horizon, and the budget impact for the National Health Service (NHS) costs alone or with personal social services (PSS) costs. Scenario 1 would identify 79 410 new AF cases (detection gap reduced by 22%). Scenario 2 would identify 70 916 (gap reduced by 19%) and Scenario 3 would identify 99 267 new cases (gap reduction 27%). These rates translate into 2639 strokes being prevented in Scenario 1, 2357 in Scenario 2, and 3299 in Scenario 3. The 3-year NHS budget impact of Scenario 1 would be £45.3 million, £3.6 million (difference ‒92.0%) with Scenario 2, and £46.3 million (difference 2.2%) in Scenario 3, but for NHS plus PSS would be ‒£48.8 million, ‒£80.4 million (64.8%), and ‒£71.3 million (46.1%), respectively.
Conclusion
Implementation of an AF risk prediction algorithm alongside standard opportunistic screening could close the AF detection gap and prevent strokes while substantially reducing NHS and PSS combined care costs.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2022. For permissions, please email: journals.permissions@oup.com.

Europace: 27 Feb 2022; epub ahead of print
Szymanski T, Ashton R, Sekelj S, Petrungaro B, ... Hill NR, Farooqui U
Europace: 27 Feb 2022; epub ahead of print | PMID: 35226101
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This program is still in alpha version.