Journal: Europace

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Abstract

Attenuated heart rate recovery is associated with higher arrhythmia recurrence and mortality following atrial fibrillation ablation.

Donnellan E, Wazni OM, Chung MK, Elshazly MB, ... Saliba W, Jaber W
Aims
Heart rate recovery (HRR), the decrease in heart rate occurring immediately after exercise, is caused by the increase in vagal activity and sympathetic withdrawal occurring after exercise and is a powerful predictor of cardiovascular events and mortality. The extent to which it impacts outcomes of atrial fibrillation (AF) ablation has not previously been studied. The aim of this study is to investigate the association between attenuated HRR and outcomes following AF ablation.
Methods and results
We studied 475 patients who underwent EST within 12 months of AF ablation. Patients were categorized into normal (>12 b.p.m.) and attenuated (≤12 b.p.m.) HRR groups. Our main outcomes of interest included arrhythmia recurrence and all-cause mortality. During a mean follow-up of 33 months, 43% of our study population experienced arrhythmia recurrence, 74% of those with an attenuated HRR, and 30% of those with a normal HRR (P < 0.0001). Death occurred in 9% of patients in the attenuated HRR group compared to 4% in the normal HRR cohort (P = 0.001). On multivariable models adjusting for cardiorespiratory fitness (CRF), medication use, left atrial size, ejection fraction, and renal function, attenuated HRR was predictive of increased arrhythmia recurrence (hazard ratio 2.54, 95% confidence interval 1.86-3.47, P < 0.0001).
Conclusion
Heart rate recovery provides additional valuable prognostic information beyond CRF. An impaired HRR is associated with significantly higher rates of arrhythmia recurrence and death following AF ablation.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: [email protected]

Europace: 18 Jan 2021; epub ahead of print
Donnellan E, Wazni OM, Chung MK, Elshazly MB, ... Saliba W, Jaber W
Europace: 18 Jan 2021; epub ahead of print | PMID: 33463688
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Abstract

On the nature of delays allowing anatomical re-entry involving the Purkinje network: a simulation study.

Vigmond EJ, Bouyssier J, Bayer J, Haïssaguerre M, Ashikaga H
Aims
Clinical observations suggest that the Purkinje network can be part of anatomical re-entry circuits in monomorphic or polymorphic ventricular arrhythmias. However, significant conduction delay is needed to support anatomical re-entry given the high conduction velocity within the Purkinje network.
Methods and results
We investigated, in computer models, whether damage rendering the Purkinje network as either an active lesion with slow conduction or a passive lesion with no excitable ionic channel, could explain clinical observations. Active lesions had compromised sodium current and a severe reduction in gap junction coupling, while passive lesions remained coupled by gap junctions, but modelled the membrane as a fixed resistance. Both types of tissue could provide significant delays of over 100 ms. Electrograms consistent with those obtained clinically were reproduced. However, passive tissue could not support re-entry as electrotonic coupling across the delay effectively increased the proximal refractory period to an extremely long interval. Active tissue, conversely, could robustly maintain re-entry.
Conclusion
Formation of anatomical re-entry using the Purkinje network is possible through highly reduced gap junctional coupling leading to slowed conduction.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: [email protected]

Europace: 18 Jan 2021; epub ahead of print
Vigmond EJ, Bouyssier J, Bayer J, Haïssaguerre M, Ashikaga H
Europace: 18 Jan 2021; epub ahead of print | PMID: 33463686
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Abstract

Epicardial adipose tissue modulates arrhythmogenesis in right ventricle outflow tract cardiomyocytes.

Lu YY, Huang SY, Lin YK, Chen YC, ... Chen SA, Chen YJ
Aims
Ventricular arrhythmia (VA) frequently occurs in fatty infiltrative cardiomyopathy or epicardial adipose tissue (EAT) abundant hearts. Right ventricular outflow tract (RVOT), commonly covered with EAT, is vital for VA genesis. This study explored whether EAT contributes to RVOT arrhythmogenesis.
Methods and results
Conventional microelectrodes and whole-cell patch clamp were used to record electrical activity and ionic currents in rabbit RVOT tissue preparation or isolated single cardiomyocytes with or without (control) connected EAT. Epicardial adipose tissue-connected (N = 6) RVOT had more portions of fibrosis than did control (N = 5) RVOT (160.3 ± 23.2 vs. 91.9 ± 13.4 μm2/mm2, P < 0.05). Epicardial adipose tissue-connected RVOT cardiomyocytes (n = 18) had lower negative resting membrane potential (-68 ± 1 vs. -73 ± 2 mV, P < 0.05); smaller action potential (AP) amplitude (108 ± 4 vs. 135 ± 6 mV, P < 0.005); and longer 90%, 50%, and 20% of AP duration repolarization (361 ± 18 vs. 309 ± 9 ms, P < 0.05; 310 ± 17 vs. 256 ± 13 ms, P < 0.05; and 182 ± 19 vs. 114 ± 24 ms, P < 0.05, respectively) than did control (n = 13) RVOT cardiomyocytes. Moreover, compared with control RVOT cardiomyocytes, EAT-connected RVOT cardiomyocytes had larger transient outward potassium currents, similar delayed rectifier potassium currents, smaller L-type calcium currents, and inward rectifier potassium currents. After ajmaline (10 μM, a sodium channel blocker) superfusion, high VA inducibility was observed through rapid pacing in EAT-connected RVOT but not in control RVOT.
Conclusions
Epicardial adipose tissue exerts distinctive electrophysiological effects on RVOT with a propensity towards VA induction, which might play a role in lipotoxicity pathogenesis-related ventricular arrhythmogenesis.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: [email protected]

Europace: 18 Jan 2021; epub ahead of print
Lu YY, Huang SY, Lin YK, Chen YC, ... Chen SA, Chen YJ
Europace: 18 Jan 2021; epub ahead of print | PMID: 33463675
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Abstract

Effects of genetic background, sex, and age on murine atrial electrophysiology.

Obergassel J, O\'Reilly M, Sommerfeld LC, Kabir SN, ... Kirchhof P, Fabritz L
Aims
Genetically altered mice are powerful models to investigate mechanisms of atrial arrhythmias, but normal ranges for murine atrial electrophysiology have not been robustly characterized.
Methods and results
We analyzed results from 221 electrophysiological (EP) studies in isolated, Langendorff-perfused hearts of wildtype mice (114 female, 107 male) from 2.5 to 17.7 months (mean 7 months) with different genetic backgrounds (C57BL/6, FVB/N, MF1, 129/Sv, Swiss agouti). Left atrial monophasic action potential duration (LA-APD), interatrial activation time (IA-AT), and atrial effective refractory period (ERP) were summarized at different pacing cycle lengths (PCLs). Factors influencing atrial electrophysiology including genetic background, sex, and age were determined. LA-APD70 was 18 ± 0.5 ms, atrial ERP was 27 ± 0.8 ms, and IA-AT was 17 ± 0.5 ms at 100 ms PCL. LA-APD was longer with longer PCL (+17% from 80 to 120 ms PCL for APD70), while IA-AT decreased (-7% from 80 to 120 ms PCL). Female sex was associated with longer ERP (+14% vs. males). Genetic background influenced atrial electrophysiology: LA-APD70 (-20% vs. average) and atrial ERP (-25% vs. average) were shorter in Swiss agouti background compared to others. LA-APD70 (+25% vs. average) and IA-AT (+44% vs. average) were longer in 129/Sv mice. Atrial ERP was longer in FVB/N (+34% vs. average) and in younger experimental groups below 6 months of age.
Conclusion
This work defines normal ranges for murine atrial EP parameters. Genetic background has a profound effect on these parameters, at least of the magnitude as those of sex and age. These results can inform the experimental design and interpretation of murine atrial electrophysiology.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: [email protected]

Europace: 18 Jan 2021; epub ahead of print
Obergassel J, O'Reilly M, Sommerfeld LC, Kabir SN, ... Kirchhof P, Fabritz L
Europace: 18 Jan 2021; epub ahead of print | PMID: 33462602
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Abstract

Risk prediction of atrial fibrillation in the community combining biomarkers and genetics.

Börschel CS, Ohlrogge AH, Geelhoed B, Niiranen T, ... Salomaa V, Schnabel RB
Aims
Classical cardiovascular risk factors (CVRFs), biomarkers, and common genetic variation have been suggested for risk assessment of atrial fibrillation (AF). To evaluate their clinical potential, we analysed their individual and combined ability of AF prediction.
Methods and results
In N = 6945 individuals of the FINRISK 1997 cohort, we assessed the predictive value of CVRF, N-terminal pro B-type natriuretic peptide (NT-proBNP), and 145 recently identified single-nucleotide polymorphisms (SNPs) combined in a developed polygenic risk score (PRS) for incident AF. Over a median follow-up of 17.8 years, n = 551 participants (7.9%) developed AF. In multivariable-adjusted Cox proportional hazard models, NT-proBNP [hazard ratio (HR) of log transformed values 4.77; 95% confidence interval (CI) 3.66-6.22; P < 0.001] and the PRS (HR 2.18; 95% CI 1.88-2.53; P < 0.001) were significantly related to incident AF. The discriminatory ability improved asymptotically with increasing numbers of SNPs. Compared with a clinical model, AF risk prediction was significantly improved by addition of NT-proBNP and the PRS. The C-statistic for the combination of CVRF, NT-proBNP, and the PRS reached 0.83 compared with 0.79 for CVRF only (P < 0.001). A replication in the Dutch Prevention of REnal and Vascular ENd-stage Disease (PREVEND) cohort revealed similar results. Comparing the highest vs. lowest quartile, NT-proBNP and the PRS both showed a more than three-fold increased AF risk. Age remained the strongest risk factor with a 16.7-fold increased risk of AF in the highest quartile.
Conclusion
The PRS and the established biomarker NT-proBNP showed comparable predictive ability. Both provided incremental predictive value over standard clinical variables. Further improvements for the PRS are likely with the discovery of additional SNPs.

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

Europace: 16 Jan 2021; epub ahead of print
Börschel CS, Ohlrogge AH, Geelhoed B, Niiranen T, ... Salomaa V, Schnabel RB
Europace: 16 Jan 2021; epub ahead of print | PMID: 33458771
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Abstract

Optimizing cryoballoon pulmonary vein isolation: lessons from >1000 procedures- the Frankfurt approach.

Bordignon S, Chen S, Bologna F, Thohoku S, ... Schmidt B, Chun JKR
Aims
Cryoballoon (CB) pulmonary vein isolation (PVI) is an accepted ablation strategy for rhythm control in atrial fibrillation (AF). We describe efficacy and safety in a high volume centre with a long experience in the use of the second-generation CB (CB2).
Methods and results
Consecutive paroxysmal AF (PAF) or persistent AF (persAF) patients undergoing CB2-PVI were enrolled. Procedural data, efficacy, and safety issues were systematically collected. The 28 mm CB2 was used in combination with an inner lumen spiral catheter, a luminal oesophageal temperature (LET) probe was used with a cut-off of 15°C, the phrenic nerve (PN) monitored during septal PVs ablation. Freeze duration was mainly set at 240 s with a bonus application in case of delayed time-to-isolation (TTI > 75 s). A total of 1017 CB2 procedures were analysed (58% male, 66 ± 12 years old, 70% with PAF). 3964 PVs were identified, 99.8% PVs isolated using solely the 28 mm CB. Mean procedure time was 69 ± 25 min, TTI during the first application was recorded in 77% of PVs after a mean of 48 ± 31 s. We recorded 0.2% cardiac tamponade, 4.8% PN injury (1.6% of PN palsy), and 19% of LET < 15°C. Among 725 patients with follow-up data, 84% with PAF and 75% with persAF were in stable SR at 1 year. Shorter freezing duration and longer TTI were procedural predictors for recurrence.
Conclusion
Cryoballoon procedures are fast and associated with a benign safety profile. Shorter TTI and longer freeze durations are associated with sinus rhythm during follow-up.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: [email protected]

Europace: 16 Jan 2021; epub ahead of print
Bordignon S, Chen S, Bologna F, Thohoku S, ... Schmidt B, Chun JKR
Europace: 16 Jan 2021; epub ahead of print | PMID: 33458770
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Abstract

Sleep apnoea has a dose-dependent effect on atrial remodelling in paroxysmal but not persistent atrial fibrillation: a high-density mapping study.

Nalliah CJ, Wong GR, Lee G, Voskoboinik A, ... Sanders P, Kalman JM
Aims
Obstructive sleep apnoea (OSA) associates with atrial fibrillation (AF), but the relationship of OSA severity and AF phenotype with the atrial substrate remains poorly defined. We sought to define the atrial substrate across the spectrum of OSA severity utilizing high-density mapping.
Methods and results
Sixty-six consecutive patients (male 71%, age 61 ± 9) having AF ablation (paroxysmal AF 36, persistent AF 30) were recruited. All patents underwent formal overnight polysomnography and high-density left atrial (LA) mapping (mean 2351 ± 1244 points) in paced rhythm. Apnoea-hypopnoea index (AHI) (mean 21 ± 18) associated with lower voltage (-0.34, P = 0.005), increased complex points (r = 0.43, P < 0.001), more low-voltage areas (r = 0.42, P < 0.001), and greater voltage heterogeneity (r = 0.39, P = 0.001), and persisted after multivariable adjustment. Atrial conduction heterogeneity (r = 0.24, P = 0.025) but not conduction velocity (r = -0.09, P = 0.50) associated with AHI. Patchy regions of low voltage that co-localized with slowed conduction defined the atrial substrate in paroxysmal AF, while a diffuse atrial substrate predominated in persistent AF. The association of AHI with remodelling was most apparent among paroxysmal AF [LA voltage: paroxysmal AF -0.015 (-0.025, -0.005), P = 0.004 vs. persistent AF -0.006 (-0.017, 0.005), P = 0.30]. Furthermore, in paroxysmal AF an AHI ≥ 30 defined a threshold at which atrial remodelling became most evident (nil-mild vs. moderate vs. severe: 1.92 ± 0.42 mV vs. 1.84 ± 0.28 mV vs. 1.34 ± 0.41 mV, P = 0.006). In contrast, significant remodelling was observed across all OSA categories in persistent AF (1.67 ± 0.55 mV vs. 1.50 ± 0.66 mV vs. 1.55 ± 0.67 mV, P = 0.82).
Conclusion
High-density mapping observed that OSA associates with marked atrial remodelling, predominantly among paroxysmal AF cohorts with severe OSA. This may facilitate the identification of AF patients that stand to derive the greatest benefit from OSA management.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: [email protected]

Europace: 13 Jan 2021; epub ahead of print
Nalliah CJ, Wong GR, Lee G, Voskoboinik A, ... Sanders P, Kalman JM
Europace: 13 Jan 2021; epub ahead of print | PMID: 33447844
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Abstract

Arrhythmogenic potential of myocardial disarray in hypertrophic cardiomyopathy: genetic basis, functional consequences and relation to sudden cardiac death.

Finocchiaro G, Sheikh N, Leone O, Westaby J, ... Sheppard MN, Olivotto I

Myocardial disarray is defined as disorganized cardiomyocyte spatial distribution, with loss of physiological fibre alignment and orientation. Since the first pathological descriptions of hypertrophic cardiomyopathy (HCM), disarray appeared as a typical feature of this condition and sparked vivid debate regarding its specificity to the disease and clinical significance as a diagnostic marker and a risk factor for sudden death. Although much of the controversy surrounding its diagnostic value in HCM persists, it is increasingly recognized that myocardial disarray may be found in physiological contexts and in cardiac conditions different from HCM, raising the possibility that central focus should be placed on its quantity and distribution, rather than a mere presence. While further studies are needed to establish what amount of disarray should be considered as a hallmark of the disease, novel experimental approaches and emerging imaging techniques for the first time allow ex vivo and in vivo characterization of the myocardium to a molecular level. Such advances hold the promise of filling major gaps in our understanding of the functional consequences of myocardial disarray in HCM and specifically on arrhythmogenic propensity and as a risk factor for sudden death. Ultimately, these studies will clarify whether disarray represents a major determinant of the HCM clinical profile, and a potential therapeutic target, as opposed to an intriguing but largely innocent bystander.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: [email protected]

Europace: 13 Jan 2021; epub ahead of print
Finocchiaro G, Sheikh N, Leone O, Westaby J, ... Sheppard MN, Olivotto I
Europace: 13 Jan 2021; epub ahead of print | PMID: 33447843
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Abstract

High-degree atrioventricular block in COVID-19 hospitalized patients.

Dagher L, Wanna B, Mikdadi G, Young M, Sohns C, Marrouche NF
Background
The novel coronavirus SARS-CoV-2 has shown the potential to significantly affect the cardiovascular system. Cardiac arrhythmias are commonly reported complications in COVID-19 hospitalized patients.
Methods
While tachyarrhythmias seem most common, we describe four cases of COVID-19 patients who developed a transient high-degree atrioventricular (AV) block during the course of their hospitalization.
Results and conclusion
All four patients who developed a high-degree AV block during their hospitalization with COVID-19 did not require permanent pacing. Similarly to most AV blocks associated with infectious organisms and given its transient nature, this case series suggests that conservative management strategies should be preferred in COVID-19 patients who develop complete heart block.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: [email protected]

Europace: 11 Jan 2021; epub ahead of print
Dagher L, Wanna B, Mikdadi G, Young M, Sohns C, Marrouche NF
Europace: 11 Jan 2021; epub ahead of print | PMID: 33432349
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Abstract

Sinus rhythm voltage fingerprinting in patients with mitral valve disease using a high-density epicardial mapping approach.

van Schie MS, Starreveld R, Bogers AJJC, de Groot NMS
Aims
Unipolar voltage (UV) mapping is increasingly used for guiding ablative therapy of atrial fibrillation (AF) as unipolar electrograms (U-EGMs) are independent of electrode orientation and atrial wavefront direction. This study was aimed at constructing individual, high-resolution sinus rhythm (SR) UV fingerprints to identify low-voltage areas and study the effect of AF episodes in patients with mitral valve disease (MVD).
Methods and results
Intra-operative epicardial mapping (interelectrode distance 2 mm) of the right and left atrium, Bachmann\'s bundle (BB), and pulmonary vein area was performed in 67 patients (27 male, 67 ± 11 years) with or without a history of paroxysmal AF (PAF). In all patients, there were considerable regional variations in voltages. UVs at BB were lower in patients with PAF compared with those without [no AF: 4.94 (3.56-5.98) mV, PAF: 3.30 (2.25-4.57) mV, P = 0.006]. A larger number of low-voltage potentials were recorded at BB in the PAF group [no AF: 2.13 (0.52-7.68) %, PAF: 12.86 (3.18-23.59) %, P = 0.001]. In addition, areas with low-voltage potentials were present in all patients, yet we did not find any predilection sites for low-voltage potentials to occur.
Conclusion
Even in SR, advanced atrial remodelling in MVD patients shows marked inter-individual and regional variation. Low UVs are even present during SR in patients without a history of AF indicating that low UVs should carefully be used as target sites for ablative therapy.

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

Europace: 11 Jan 2021; epub ahead of print
van Schie MS, Starreveld R, Bogers AJJC, de Groot NMS
Europace: 11 Jan 2021; epub ahead of print | PMID: 33432326
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Abstract

Using machine learning to identify local cellular properties that support re-entrant activation in patient-specific models of atrial fibrillation.

Corrado C, Williams S, Roney C, Plank G, O\'Neill M, Niederer S
Aims
Atrial fibrillation (AF) is sustained by re-entrant activation patterns. Ablation strategies have been proposed that target regions of tissue that may support re-entrant activation patterns. We aimed to characterize the tissue properties associated with regions that tether re-entrant activation patterns in a validated virtual patient cohort.
Methods and results
Atrial fibrillation patient-specific models (seven paroxysmal and three persistent) were generated and validated against local activation time (LAT) measurements during an S1-S2 pacing protocol from the coronary sinus and high right atrium, respectively. Atrial models were stimulated with burst pacing from three locations in the proximity of each pulmonary vein to initiate re-entrant activation patterns. Five atria exhibited sustained activation patterns for at least 80 s. Models with short maximum action potential durations (APDs) were associated with sustained activation. Phase singularities were mapped across the atria sustained activation patterns. Regions with a low maximum conduction velocity (CV) were associated with tethering of phase singularities. A support vector machine (SVM) was trained on maximum local conduction velocity and action potential duration to identify regions that tether phase singularities. The SVM identified regions of tissue that could support tethering with 91% accuracy. This accuracy increased to 95% when the SVM was also trained on surface area.
Conclusion
In a virtual patient cohort, local tissue properties, that can be measured (CV) or estimated (APD; using effective refractory period as a surrogate) clinically, identified regions of tissue that tether phase singularities. Combing CV and APD with atrial surface area further improved the accuracy in identifying regions that tether phase singularities.

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

Europace: 11 Jan 2021; epub ahead of print
Corrado C, Williams S, Roney C, Plank G, O'Neill M, Niederer S
Europace: 11 Jan 2021; epub ahead of print | PMID: 33437987
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Abstract

Quantitative collagen assessment in right ventricular myectomies from patients with tetralogy of Fallot.

Wülfers EM, Greiner J, Giese M, Madl J, ... Rog-Zielinska EA, Fürniss HE
Aims
Patients with tetralogy of Fallot (TOF) are often affected by right ventricular fibrosis, which has been associated with arrhythmias. This study aimed to assess fibrosis distribution in right ventricular outflow tract (RVOT) myocardium of TOF patients to evaluate the utility of single histology-section analyses, and to explore the possibility of fibrosis quantification in unlabelled tissue by second harmonic generation imaging (SHGI) as an alternative to conventional histology-based assays.
Methods and results
We quantified fibrosis in 11 TOF RVOT samples, using a tailor-made automated image analysis method on Picrosirius red-stained sections. In a subset of samples, histology- and SHGI-based fibrosis quantification approaches were compared. Fibrosis distribution was highly heterogeneous, with significant and comparable variability between and within samples. We found that, on average, 67.8 mm2 of 10 µm thick, histologically processed tissue per patient had to be analysed for accurate fibrosis quantification. SHGI provided data faster and on live tissue, additionally enabling quantification of collagen anisotropy.
Conclusion
Given the high intra-individual heterogeneity, fibrosis quantification should not be conducted on single sections of TOF RVOT myectomies. We provide an analysis algorithm for fibrosis quantification in histological images, which enables the required extended volume analyses in these patients.

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

Europace: 05 Jan 2021; epub ahead of print
Wülfers EM, Greiner J, Giese M, Madl J, ... Rog-Zielinska EA, Fürniss HE
Europace: 05 Jan 2021; epub ahead of print | PMID: 33404047
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Abstract

Long-term oral anticoagulant after catheter ablation for atrial fibrillation.

Chew D, Piccini JP

Catheter ablation is superior to antiarrhythmic therapy for the reduction of symptomatic atrial fibrillation (AF), recurrence, and burden. The possibility of a true \'rhythm\' control strategy with catheter ablation has re-opened the debate on rate vs. rhythm control and the subsequent impact on stroke risk. Some observation studies suggest that successful AF catheter ablation and maintenance of sinus rhythm are associated with a decrease in stroke risk, while the CABANA trial had demonstrated no apparent reduction. Other observational studies have demonstrated increased stroke risk when oral anticoagulation (OAC) is discontinued after catheter ablation. When and in whom OAC can be discontinued after ablation will need to be determined in properly conducted randomized control trials. In this review article, we discuss our current understanding of the interactions between AF, stroke, and anticoagulation following catheter ablation. Specifically, we discuss the evidence for the long-term anticoagulation following successful catheter ablation, the potential for OAC discontinuation with restoration of sinus rhythm, and novel approaches to anticoagulation management post-ablation.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: [email protected]

Europace: 04 Jan 2021; epub ahead of print
Chew D, Piccini JP
Europace: 04 Jan 2021; epub ahead of print | PMID: 33400774
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Abstract

Mechanical circulatory support in the management of life-threatening arrhythmia.

Della Bella P, Radinovic A, Limite LR, Baratto F

Life-threatening refractory unstable ventricular arrhythmias in presence of advanced heart failure (HF) may determine haemodynamic impairment. Haemodynamic mechanical support (HMS) in this setting has a relevant role to restore end-organ perfusion. Catheter ablation (CA) of ventricular tachycardia (VT) is effective at achieving rhythm stabilization, allowing patient\'s weaning from HMS, or bridging to permanent HF treatments. Acute heart decompensation during CA at anaesthesia induction in presence of advanced heart disease, in selected cases requires a preemptive HMS to prevent periprocedure adverse outcomes. Substrate ablation during sinus rhythm (SR) might be an effective strategy of ablation in presence of unstable VTs; however, in a minority of patients, it might have some limitations and might be unfeasible in some settings, including the case of the mechanical induction of several unstable VTs and the absence of ablation targets. In case of the persistent induction of unstable VTs after a previous failure of a substrate-based ablation in SR, a feasible alternative strategy of ablation might be VT activation/entrainment mapping supported by HMS. Multiple devices are available for HMS in the low-output states related to electrical storm and during CA of VT. The choice of the device is not standardized and it is based on the centres\' expertise. The aim of this article is to provide an up-to-date review on HMS for the management of life-threatening arrhythmias, in the context of catheter ablation and discussing our approach to manage critical VT patients.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: [email protected]

Europace: 30 Dec 2020; epub ahead of print
Della Bella P, Radinovic A, Limite LR, Baratto F
Europace: 30 Dec 2020; epub ahead of print | PMID: 33382868
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Abstract

Post-operative pain following cardiac implantable electronic device implantation: insights from the BRUISE CONTROL trials.

Nair GM, Birnie DH, Sumner GL, Krahn AD, ... Wells GA, Essebag V
Aims 
Post-operative pain following cardiac implantable electronic device (CIED) insertion is associated with patient dissatisfaction, emotional distress, and emergency department visits. We sought to identify factors associated with post-operative pain and develop a prediction score for post-operative pain.
Methods and results 
All patients from the BRUISE CONTROL-1 and 2 trials were included in this analysis. A validated Visual Analogue Scale (VAS) was used to assess the severity of pain related to CIED implant procedures. Patients were asked to grade the most severe post-operative pain, average post-operative pain, and pain on the day of the first post-operative clinic. Multivariable regression analyses were performed to identify predictors of significant post-operative pain and to develop a pain-prediction score. A total of 1308 patients were included. Multivariable regression analysis found that the presence of post-operative clinically significant haematoma {CSH; P value < 0.001; odds ratio (OR) 3.82 [95% confidence interval (CI): 2.37-6.16]}, de novo CIED implantation [P value < 0.001; OR 1.90 (95% CI: 1.47-2.46)], female sex [P value < 0.001; OR 1.61 (95% CI: 1.22-2.12)], younger age [<65 years; P value < 0.001; OR 1.54 (95% CI: 1.14-2.10)], and lower body mass index [<20 kg/m2; P value < 0.05; OR 2.05 (95% CI: 0.98-4.28)] demonstrated strong and independent associations with increased post-operative pain. An 11-point post-operative pain prediction score was developed using the data.
Conclusion 
Our study has identified multiple predictors of post-operative pain after CIED insertion. We have developed a prediction score for post-operative pain that can be used to identify individuals at risk of experiencing significant post-operative pain.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: [email protected]

Europace: 27 Dec 2020; epub ahead of print
Nair GM, Birnie DH, Sumner GL, Krahn AD, ... Wells GA, Essebag V
Europace: 27 Dec 2020; epub ahead of print | PMID: 33367623
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Abstract

A simple and practical criterion for determining a failed His-bundle pacing.

Liang Y, Wang N, Yu H, Xu B, ... Wang Z, Han Y
Aims
To establish a simple criterion for determining a failed His-bundle pacing (HBP). This criterion states that if stimulus to QRS end interval is longer than His-bundle potential to QRS end interval (\'S-QRSend > H-QRSend\') then a failed HBP can be determined.
Methods and results
We performed retrospective analysis on 737 pacing tests around His-bundle in 241 patients and prospective analysis on 400 tests in 123 patients. A successful HBP is defined as that whole His-bundle is captured with or without capture of adjacent ventricular myocardium, otherwise, a failed HBP was considered. The output criteria and effective refractory period criteria were used as the gold standards for determining a successful HBP. The gold standards are that if decreasing the pacing output or pacing cycle length to a certain level results in duration or morphology changes of QRS, then a successful HBP is ascertained. In retrospective analysis of patients with normal His-Purkinje conduction, a failed HBP was determined in 31% (154/492) of pacing tests according to \'S-QRSend > H-QRSend\'; all of them were validated by the gold standards (specificity = 100%). In prospective study, a failed HBP was confirmed according to the simple criterion with 100% accuracy in 33% (79/241) pacing tests. This simple criterion was also suitable for patients with His-Purkinje conduction disease although cases with \'S-QRSend > H-QRSend\' rarely occurred.
Conclusion
A failed HBP can be easily and reliably determined solely by \'S-QRSend > H-QRSend\' in more than 30% pacing tests.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: [email protected]

Europace: 25 Dec 2020; 22:ii61-ii66
Liang Y, Wang N, Yu H, Xu B, ... Wang Z, Han Y
Europace: 25 Dec 2020; 22:ii61-ii66 | PMID: 33083840
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Impact:
Abstract

Novel left ventricular cardiac synchronization: left ventricular septal pacing or left bundle branch pacing?

Wu S, Sharma PS, Huang W

It is well recognized that a high burden of right ventricular pacing results in deleterious clinical outcomes over the long term. His bundle pacing can achieve optimal ventricular synchronization; however, relatively high pacing thresholds, low R-wave amplitudes, and the long-term performance have been concerns. Recently, left ventricular (LV) septal endocardium pacing (LVSP) has demonstrated improved acute haemodynamics. Another novel technique of intraseptal left bundle branch pacing (LBBP) via transvenous approach has been adopted rapidly and has demonstrated its feasibility and effectiveness. This article reviews the clinical application and differences between LVSP and LBBP. Compared with LVSP, LBBP has strict criteria for left conduction system capture and lead location. In addition to LV septal capture it also stimulates the proximal left bundle branch, resulting in rapid and physiological LV activation. With a uniformity and standardization of the implant procedure and definitions, it may be possible to achieve widespread application of this form of physiological pacing.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: [email protected]

Europace: 25 Dec 2020; 22:ii10-ii18
Wu S, Sharma PS, Huang W
Europace: 25 Dec 2020; 22:ii10-ii18 | PMID: 33370804
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Impact:
Abstract

Electrical characteristics of pacing different portions of the His bundle in bradycardia patients.

Hu Y, Gu M, Hua W, Niu H, ... Liu X, Zhang S
Aims
His-bundle pacing (HBP) can be achieved in either atrial-side HBP (aHBP) or ventricular-side HBP (vHBP). The study compared the pacing parameters and electrophysiological characteristics between aHBP and vHBP in bradycardia patients.
Methods and results
Fifty patients undergoing HBP implantation assisted by visualization of the tricuspid valvular annulus (TVA) were enrolled. The HBP lead position was identified by TVA angiography. Twenty-five patients were assigned to undergo aHBP and compared with 25 patients who underwent vHBP primarily in a prospective and randomized fashion. Pacing parameters and echocardiography were routinely assessed at implant and 3-month follow-up. His-bundle pacing was successfully performed in 45 patients (90% success rate with 44.4% aHBP and 55.6% vHBP). The capture threshold was lower in vHBP than aHBP at implant (vHBP: 1.1 ± 0.5 vs. aHBP: 1.4 ± 0.4 V/1.0 ms, P = 0.014) and 3-month follow-up (vHBP: 0.8 ± 0.4 vs. aHBP: 1.7 ± 0.8 V/0.4 ms, P < 0.001). The R-wave amplitude was higher in vHBP than in aHBP at implant (vHBP: 4.5 ± 1.4 vs. aHBP: 2.0 ± 0.8 mV, P < 0.001) and at 3-month follow-up (vHBP: 4.4 ± 1.5 vs. aHBP: 1.8 ± 0.7 mV, P < 0.001). No procedure-related complications and aggravation of tricuspid valve regurgitation were observed in most patients and echocardiographic assessment of cardiac function remained in the normal range in all patients during the follow-up.
Conclusion
This study demonstrates that vHBP features a low and stable pacing capture threshold and high R-wave amplitude, suggesting better pacing mode management and battery longevity can be achieved by HBP in the ventricular side.

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Europace: 25 Dec 2020; 22:ii27-ii35
Hu Y, Gu M, Hua W, Niu H, ... Liu X, Zhang S
Europace: 25 Dec 2020; 22:ii27-ii35 | PMID: 33370803
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Impact:
Abstract

Lead performance and clinical outcomes of patients with permanent His-Purkinje system pacing: a single-centre experience.

Qian Z, Qiu Y, Wang Y, Jiang Z, ... Hou X, Zou J
Aims
His-Purkinje system (HPS) pacing, including His bundle (HB) and left bundle branch (LBB) pacing, has emerged as a highlighted topic in recent years. Comparisons in lead performance and clinical outcomes between HB and LBB pacing were seldom reported. We aimed to investigate the mid-long-term lead performance and clinical outcomes of permanent HPS pacing patients in our centre.
Methods and results
Permanent HB pacing was implemented by placing the pacing lead helix at the HB area. Left bundle branch pacing was achieved by placing the lead helix in the left-side sub-endocardium of the interventricular septum. Pacing parameters, 12-lead ECG, echocardiography, and clinical outcomes were evaluated during follow-up. A total of 64 patients with HB pacing and 185 with LBB pacing were included. Left bundle branch pacing exhibited a slightly longer paced QRS duration than HB pacing (117.7 ± 11.0 vs. 113.7 ± 19.8 ms, P = 0.04). Immediate post-operation, LBB pacing had a significant higher R-wave amplitude (16.5 ± 7.5 vs. 4.3 ± 3.6 mV, P < 0.001) and lower capture threshold (0.5 ± 0.1 vs. 1.2 ± 0.8 V, P < 0.001) compared with HB pacing. During follow-up, an increase in capture threshold of >1.0 V from baseline was found in eight (12.5%) patients in the HB pacing group and none in LBB pacing. Paced QRS morphology changed from Qr to QS in lead V1 in seven patients (3.8%) with LBB pacing. Both HB and LBB pacing preserved cardiac function in patients with left ventricular ejection fraction (LVEF) over 50%. In patients with LVEF <50%, both HB and LBB pacing improved clinical outcomes during follow-up.
Conclusion
His-Purkinje system pacing produced favourable electrical synchrony and improved cardiac function in patients with heart failure. Left bundle branch pacing showed superior pacing parameters over HB pacing. Lead micro-displacement with changes in paced QRS morphology posts a concern in LBB pacing.

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Europace: 25 Dec 2020; 22:ii45-ii53
Qian Z, Qiu Y, Wang Y, Jiang Z, ... Hou X, Zou J
Europace: 25 Dec 2020; 22:ii45-ii53 | PMID: 33370802
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Impact:
Abstract

Feasibility and efficacy of left bundle branch area pacing in patients indicated for cardiac resynchronization therapy.

Li Y, Yan L, Dai Y, Zhou Y, ... Chen K, Zhang S
Aims
The present study was to evaluate the feasibility and clinical outcomes of left bundle branch area pacing (LBBAP) in cardiac resynchronization therapy (CRT)-indicated patients.
Methods and results
LBBAP was performed via transventricular septal approach in 25 patients as a rescue strategy in 5 patients with failed left ventricular (LV) lead placement and as a primary strategy in the remaining 20 patients. Pacing parameters, procedural characteristics, electrocardiographic, and echocardiographic data were assessed at implantation and follow-up. Of 25 enrolled CRT-indicated patients, 14 had left bundle branch block (LBBB, 56.0%), 3 right bundle branch block (RBBB, 12.0%), 4 intraventricular conduction delay (IVCD, 16.0%), and 4 ventricular pacing dependence (16.0%). The QRS duration (QRSd) was significantly shortened by LBBAP (intrinsic 163.6 ± 29.4 ms vs. LBBAP 123.0 ± 10.8 ms, P < 0.001). During the mean follow-up of 9.1 months, New York Heart Association functional class was improved to 1.4 ± 0.6 from baseline 2.6 ± 0.6 (P < 0.001), left ventricular ejection fraction (LVEF) increased to 46.9 ± 10.2% from baseline 35.2 ± 7.0% (P < 0.001), and LV end-diastolic dimensions (LVEDD) decreased to 56.8 ± 9.7 mm from baseline 64.1 ± 9.9 mm (P < 0.001). There was a significant improvement (34.1 ± 7.4% vs. 50.0 ± 12.2%, P < 0.001) in LVEF in patients with LBBB.
Conclusion
The present study demonstrates the clinical feasibility of LBBAP in CRT-indicated patients. Left bundle branch area pacing generated narrow QRSd and led to reversal remodelling of LV with improvement in cardiac function. LBBAP may be an alternative to CRT in patients with failure of LV lead placement and a first-line option in selected patients such as those with LBBB and heart failure.

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Europace: 25 Dec 2020; 22:ii54-ii60
Li Y, Yan L, Dai Y, Zhou Y, ... Chen K, Zhang S
Europace: 25 Dec 2020; 22:ii54-ii60 | PMID: 33370801
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Impact:
Abstract

Long-term performance and risk factors analysis after permanent His-bundle pacing and atrioventricular node ablation in patients with atrial fibrillation and heart failure.

Su L, Cai M, Wu S, Wang S, ... Vijayaraman P, Huang W
Aims
His-bundle pacing (HBP) combined with atrioventricular node (AVN) ablation has been demonstrated to be effective in patients with atrial fibrillation (AF) and heart failure (HF) during medium-term follow-up and there are limited data on the risk analysis of adverse prognosis in this population. In this study, we aimed to evaluate the long-term performance of HBP following AVN ablation in AF and HF.
Methods and results
From August 2012 to December 2017, consecutive AF patients with HF and narrow QRS who underwent AVN ablation and HBP were enrolled. The clinical and echocardiographic data, pacing parameters, all-cause mortality, and heart failure hospitalization (HFH) were tracked. A total of 94 patients were enrolled (age 70.1 ± 10.5 years; male 57.4%). Acute HBP were achieved in 89 (94.7%) patients with successful permanent HBP combined with AVN ablation in 81 (86.2%) patients. Left ventricular ejection fraction (LVEF) improved from 44.9 ± 14.9% at baseline to 57.6 ± 12.5% during a median follow-up of 3.0 (IQR: 2.0-4.4) years (P < 0.001). Heart failure hospitalization or all-cause mortality occurred in 21 (25.9%) patients. The LVEF ≤ 40%, pulmonary artery systolic pressure (PASP) ≥40 mmHg, or serum creatinine (Scr) ≥97 μmol/L at baseline was significantly associated with higher composite endpoint of HFH or death (P < 0.05). The His capture threshold was 1.0 ± 0.7 V/0.5 ms at implant and remained stable during follow-up.
Conclusion
His-bundle pacing combined with AVN ablation was effective in patients with AF and drug-refectory HF. High PASP, high Scr, or low LVEF at baseline was independent predictors of composite endpoint of all-cause mortality or HFH.

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Europace: 25 Dec 2020; 22:ii19-ii26
Su L, Cai M, Wu S, Wang S, ... Vijayaraman P, Huang W
Europace: 25 Dec 2020; 22:ii19-ii26 | PMID: 33370800
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Impact:
Abstract

The feasibility and safety of left bundle branch pacing vs. right ventricular pacing after mid-long-term follow-up: a single-centre experience.

Chen X, Jin Q, Bai J, Wang W, ... Su Y, Ge J
Aims
The aim of this study is to prospectively assess the feasibility and safety of left bundle branch pacing (LBBP) when compared with right ventricular pacing (RVP) during mid-long-term follow-up in a large cohort.
Methods and results
Patients (n = 554) indicated for pacemaker implantation were prospectively and consecutively enrolled and were non-randomized divided into LBBP group and RVP group. The levels of cTnT and N-terminal pro-B type natriuretic peptide were measured and compared within 2 days post-procedure between two groups. Implant characteristics, procedure-related complications, and clinical outcomes were also compared. Pacing thresholds, sensing, and impedance were assessed during procedure and follow-up. Left bundle branch pacing was feasible with a success rate of 94.8% with high incidence of LBB potential (89.9%), selective LBBP (57.8%), and left deviation of paced QRS axis (79.7%) with mean Sti-LVAT of 65.07 ± 8.58 ms. Paced QRS duration was significantly narrower in LBBP when compared with RVP (132.02 ± 7.93 vs. 177.68 ± 15.58 ms, P < 0.0001) and the pacing parameters remained stable in two groups during 18 months follow-up. cTnT elevation was more significant in LBBP when compared with RVP within 2 days post-procedure (baseline: 0.03 ± 0.03 vs. 0.02 ± 0.03 ng/mL, P = 0.002; 1 day post-procedure: 0.13 ± 0.09 vs. 0.04 ± 0.03 ng/mL, P < 0.001; 2 days post-procedure: 0.10 ± 0.08 vs. 0.03 ± 0.08 ng/mL, P < 0.001). The complications and cardiac outcomes were not significantly different between two groups.
Conclusion
Left bundle branch pacing was feasible in bradycardia patients associated with stable pacing parameters during 18 months follow-up. Paced QRS duration was significantly narrower than that of RVP. Though cTnT elevation was more significant in LBBP within 2 days post-procedure, the complications, and cardiac outcomes were not significantly different between two groups.

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Europace: 25 Dec 2020; 22:ii36-ii44
Chen X, Jin Q, Bai J, Wang W, ... Su Y, Ge J
Europace: 25 Dec 2020; 22:ii36-ii44 | PMID: 33370799
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Impact:
Abstract

Brugada syndrome and syncope: a practical approach for diagnosis and treatment.

Mascia G, Bona RD, Ameri P, Canepa M, ... Crotti L, Brignole M

Syncope in patients with Brugada electrocardiogram pattern may represent a conundrum in the decision algorithm because incidental benign forms, especially neurally mediated syncope, are very frequent in this syndrome similarly to the general population. Arrhythmic syncope in Brugada syndrome typically results from a self-terminating sustained ventricular tachycardia or paroxysmal ventricular fibrillation, potentially leading to sudden cardiac death. Distinguishing syncope due to malignant arrhythmias from a benign form is often difficult unless an electrocardiogram is recorded during the episode. We performed a review of the existing literature and propose a practical approach for diagnosis and treatment of the patients with Brugada syndrome and syncope.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: [email protected]

Europace: 25 Dec 2020; epub ahead of print
Mascia G, Bona RD, Ameri P, Canepa M, ... Crotti L, Brignole M
Europace: 25 Dec 2020; epub ahead of print | PMID: 33367713
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Impact:
Abstract

Predictors of recurrence after durable pulmonary vein isolation for paroxysmal atrial fibrillation.

Lycke M, Kyriakopoulou M, El Haddad M, Wielandts JY, ... Duytschaever M, Knecht S
Aims
Catheter ablation of paroxysmal atrial fibrillation (AF) reduces AF recurrence, AF burden, and improves quality of life. Data on clinical and procedural predictors of arrhythmia recurrence are scarce and are flawed by the high rate of pulmonary vein reconnection evidenced during repeat procedures after pulmonary vein isolation (PVI). In this study, we identified clinical and procedural predictors for AF recurrence 1 year after CLOSE-guided PVI, as this strategy has been associated with an increased PVI durability.
Methods and results
Patients with paroxysmal AF, who received CLOSE-guided PVI and who participated in a prospective trial in our centre, were included in this study. Uni- and multivariate models were plotted to find clinical and procedural predictors for AF recurrence within 1 year. Three hundred twenty-five patients with a mean age of 63 years (CHA2DS2VASc 1 [1-3], left atrium diameter 41 ± 6 mm) were included. About 60.9% were male individuals. After 1 year, AF recurrence occurred in 10.5% of patients. In a binary logistic regression analysis, the diagnosis-to-ablation time (DAT) was found to be the strongest predictor of AF recurrence (P = 0.011). Diagnosis-to-ablation time ≥1 year was associated with a nearly two-fold increased risk for developing AF recurrence.
Conclusion
The DAT is the most important predictor of arrhythmia recurrence in low-risk patients treated with durable pulmonary vein isolation for paroxysmal AF. Whether reducing the DAT could improve long-term outcomes should be investigated in another trial.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: [email protected]

Europace: 25 Dec 2020; epub ahead of print
Lycke M, Kyriakopoulou M, El Haddad M, Wielandts JY, ... Duytschaever M, Knecht S
Europace: 25 Dec 2020; epub ahead of print | PMID: 33367708
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Impact:
Abstract

Long-term observation of catheter ablation vs. pharmacotherapy in the management of persistent and long-standing persistent atrial fibrillation (CAPA study).

Wu G, Huang H, Cai L, Yang Y, ... Huang C,
Aims 
The roles of radiofrequency catheter ablation (RFCA) and pharmacotherapy in treating persistent and long-standing persistent atrial fibrillation (AF) have not been sufficiently investigated. We conducted a multicentre, randomized, controlled trial to compare the effects of RFCA and pharmacotherapy on the prognosis of these patients.
Methods and results 
A total of 648 patients with persistent and long-standing persistent AF were enrolled from 30 centres and randomized to either the ablation group (n = 327) or the pharmacotherapy group (n = 321). After 54.2 ± 10.6 months of follow-up, the primary endpoints occurred significantly more rarely in the ablation group than in the pharmacotherapy group (10.4% vs. 17.4%; hazard ratio 0.59, 95% confidence interval 0.48-0.75; P < 0.001). The incidence of stroke/transient ischaemic attack (TIA) was significantly lower in the ablation group (4.2% vs. 7.2%, P < 0.001). Likewise, the incidence of new-onset congestive heart failure (CHF) was lower in the ablation group (2.8% vs. 7.2%, P < 0.001). More patients had sinus rhythm in the ablation group than in the pharmacotherapy group (60.6% vs. 20.9%, P < 0.001), but fewer patients were on antiarrhythmic drugs (24.4% vs. 41.6%, P < 0.001) and warfarin (60.8% vs. 83.9%, P = 0.001). Both the 6-min walk distance and the quality of life (QoL) were improved in the ablation group at the end of follow-up.
Conclusion 
In patients with persistent and long-standing persistent AF, RFCA-based treatment was superior to pharmacotherapy in decreasing stroke/TIA and new-onset CHF and improving QoL.

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Europace: 25 Dec 2020; epub ahead of print
Wu G, Huang H, Cai L, Yang Y, ... Huang C,
Europace: 25 Dec 2020; epub ahead of print | PMID: 33367669
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Impact:
Abstract

Life-threatening arrhythmias with autosomal recessive TECRL variants.

Webster G, Aburawi EH, Chaix MA, Chandler S, ... Wilde AAM, Bhuiyan ZA
Aims 
Sudden death and aborted sudden death have been observed in patients with biallelic variants in TECRL. However, phenotypes have only begun to be described and no data are available on medical therapy after long-term follow-up.
Methods and results 
An international, multi-centre retrospective review was conducted. We report new cases associated with TECRL variants and long-term follow-up from previously published cases. We present 10 cases and 37 asymptomatic heterozygous carriers. Median age at onset of cardiac symptoms was 8 years (range 1-22 years) and cases were followed for an average of 10.3 years (standard deviation 8.3), right censored by death in three cases. All patients on metoprolol, bisoprolol, or atenolol were transitioned to nadolol or propranolol due to failure of therapy. Phenotypes typical of both long QT syndrome and catecholaminergic polymorphic ventricular tachycardia (CPVT) were observed. We also observed divergent phenotypes in some cases despite identical homozygous variants. None of 37 heterozygous family members had a cardiac phenotype.
Conclusion 
Patients with biallelic pathogenic TECRL variants present with variable cardiac arrhythmia phenotypes, including those typical of long QT syndrome and CPVT. Nadolol and propranolol may be superior beta-blockers in this setting. No cardiac disease or sudden death was present in patients with a heterozygous genotype.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: [email protected]

Europace: 24 Dec 2020; epub ahead of print
Webster G, Aburawi EH, Chaix MA, Chandler S, ... Wilde AAM, Bhuiyan ZA
Europace: 24 Dec 2020; epub ahead of print | PMID: 33367594
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Impact:
Abstract

Pregnancies, ventricular arrhythmias, and substrate progression in women with arrhythmogenic right ventricular cardiomyopathy in the Nordic ARVC Registry.

Platonov PG, Castrini AI, Svensson A, Christiansen MK, ... Haugaa KH, Svendsen JH
Aims
Women with arrhythmogenic right ventricular cardiomyopathy (ARVC) are at relatively lower risk of ventricular arrhythmias (VAs) than men, but the physical burden associated with pregnancy on VA risk remains insufficiently studied. We aimed to assess the risk of VA in relation to pregnancies in women with ARVC.
Methods and results
We included 199 females with definite ARVC (n = 121) and mutation-positive family members without ascertained ARVC diagnosis (n = 78), of whom 120 had at least one childbirth. Ventricular arrhythmia-free survival after the latest childbirth was compared between women with one (n = 20), two (n = 67), and three or more (n = 37) childbirths. Cumulative probability of VA for each pregnancy (n = 261) was assessed from conception through 2 years after childbirth and compared between those pregnancies that occurred before (n = 191) or after (n = 19) ARVC diagnosis and in mutation-positive family members (n = 51). The nulliparous women had lower median age at ARVC diagnosis (38 vs. 42 years, P < 0.001) and first VA (22 vs. 41 years, P < 0.001). Ventricular arrhythmia-free survival after the latest childbirth was not related to the number of pregnancies. No pregnancy-related VA was reported among the family members. Women who gave birth after ARVC diagnosis had elevated risk of VA postpartum (hazard ratio 13.74, 95% confidence interval 2.9-63, P = 0.001), though only two events occurred during pregnancies.
Conclusion
In women with ARVC, pregnancy was uneventful for the overwhelming majority and the number of prior completed pregnancies was not associated with VA risk. Pregnancy-related VA was primarily related to the phenotypical severity rather than pregnancy itself.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: [email protected]

Europace: 22 Dec 2020; 22:1873-1879
Platonov PG, Castrini AI, Svensson A, Christiansen MK, ... Haugaa KH, Svendsen JH
Europace: 22 Dec 2020; 22:1873-1879 | PMID: 32681178
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Impact:
Abstract

The combined novel KCNQ1 frameshift I145Sfs*92 and nonsense W392X variants caused Jervell and Lange-Nielsen syndrome in a Chinese infant presenting with sustained foetal bradycardia.

Zhang Y, Li X, Yang Y, Wang J, Gao X, Fan M
Aims
We report clinical and molecular analysis of an infant presenting with foetal bradycardia and clinical outcome of Jervell and Lange-Nielsen syndrome (JLNS).
Methods and results
Clinical, electrocardiogram (ECG), and echocardiographic data were collected from members in a three-generation family. Whole exomes were amplified and sequenced for proband. The identified variants were verified in the remaining members. The pathogenicity of candidate variants was predicted using multiple software programmes. A 28-year-old non-consanguineous Chinese woman at 23 weeks\' gestation presenting with sustained foetal bradycardia of 100 b.p.m. Immunological disorders and infection were excluded. The infant was delivered at 37 weeks\' gestation with 2700-g birthweight. QTc was prolonged in both ECG and Holter recording. Hearing tests confirmed bilateral sensorineural hearing loss. Genetic testing demonstrated that the infant carried a novel frameshift c.431delC (p.I145Sfs*92) and a novel nonsense c.1175G>A (p.W392X) compound variants of KCNQ1 inherited from mother and father, respectively, in autosomal recessive inheritance. Only relative II-5 carrying heterozygous KCNQ1-I145Sfs*92 variant had prolonged QTc, while the other carriers did not have prolonged QT, suggesting an autosomal dominant inheritance of LQT1 phenotype with incomplete penetrance in the family.
Conclusion
We report the novel frameshift KCNQ1-I145Sfs*92 and nonsense KCNQ1-W392X compound variants in autosomal recessive inheritance that caused JLNS presenting as sustained foetal bradycardia for the first time. Meanwhile, KCNQ1-I145Sfs*92 heterozygous variant demonstrated LQT1 phenotype in autosomal dominant inheritance with incomplete penetrance.

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Europace: 22 Dec 2020; 22:1880-1884
Zhang Y, Li X, Yang Y, Wang J, Gao X, Fan M
Europace: 22 Dec 2020; 22:1880-1884 | PMID: 32830254
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Impact:
Abstract

Left atrial fibrosis predicts left ventricular ejection fraction response after atrial fibrillation ablation in heart failure patients: the Fibrosis-HF Study.

Kirstein B, Neudeck S, Gaspar T, Piorkowski J, ... Huo Y, Piorkowski C
Aims
Atrial fibrillation (AF) and heart failure (HF) often coexist. Catheter ablation has been reported to restore left ventricular (LV) function but patients benefit differently. This study investigated the correlation between left atrial (LA) fibrosis extent and LV ejection fraction (LVEF) recovery after AF ablation.
Methods and results
In this study, 103 patients [64 years, 69% men, 79% persistent AF, LVEF 33% interquartile range (IQR) (25-38)] undergoing first time AF ablation were investigated. Identification of LA fibrosis and selection of ablation strategy were based on sinus rhythm voltage mapping. Continuous rhythm monitoring was used to assess ablation success. Improvement in post-ablation LVEF was measured as primary study endpoint. An absolute increase in post-ablation LVEF ≥10% was defined as \'Super Response\'. Left atrial fibrosis was present in 38% of patients. After ablation LVEF increased by absolute 15% (IQR 6-25) (P < 0.001). Left ventricular ejection fraction improvement was higher in patients without LA fibrosis [15% (IQR 10-25) vs. 10% (IQR 0-20), P < 0.001]. An inverse correlation between LVEF improvement and the extent of LA fibrosis was found (R2 = 0.931). In multivariate analysis, the presence of LA fibrosis was the only independent predictor for failing LVEF improvement [odds ratio 7.2 (95% confidence interval 2.2-23.4), P < 0.001]. Echocardiographic \'Super Response\' was observed in 55/64 (86%) patients without and 21/39 (54%) patients with LA fibrosis, respectively (P < 0.001).
Conclusion
Presence and extent of LA fibrosis predict LVEF response in HF patients undergoing AF ablation. The assessment of LA fibrosis may impact prognostic stratification and clinical management in HF patients with AF.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: [email protected]

Europace: 22 Dec 2020; 22:1812-1821
Kirstein B, Neudeck S, Gaspar T, Piorkowski J, ... Huo Y, Piorkowski C
Europace: 22 Dec 2020; 22:1812-1821 | PMID: 32830233
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Impact:
Abstract

Electrocardiographic features of 431 consecutive, critically ill COVID-19 patients: an insight into the mechanisms of cardiac involvement.

Bertini M, Ferrari R, Guardigli G, Malagù M, ... Aschieri D, Rapezzi C
Aims
Our aim was to describe the electrocardiographic features of critical COVID-19 patients.
Methods and results
We carried out a multicentric, cross-sectional, retrospective analysis of 431 consecutive COVID-19 patients hospitalized between 10 March and 14 April 2020 who died or were treated with invasive mechanical ventilation. This project is registered on ClinicalTrials.gov (identifier: NCT04367129). Standard ECG was recorded at hospital admission. ECG was abnormal in 93% of the patients. Atrial fibrillation/flutter was detected in 22% of the patients. ECG signs suggesting acute right ventricular pressure overload (RVPO) were detected in 30% of the patients. In particular, 43 (10%) patients had the S1Q3T3 pattern, 38 (9%) had incomplete right bundle branch block (RBBB), and 49 (11%) had complete RBBB. ECG signs of acute RVPO were not statistically different between patients with (n = 104) or without (n=327) invasive mechanical ventilation during ECG recording (36% vs. 28%, P = 0.10). Non-specific repolarization abnormalities and low QRS voltage in peripheral leads were present in 176 (41%) and 23 (5%), respectively. In four patients showing ST-segment elevation, acute myocardial infarction was confirmed with coronary angiography. No ST-T abnormalities suggestive of acute myocarditis were detected. In the subgroup of 110 patients where high-sensitivity troponin I was available, ECG features were not statistically different when stratified for above or below the 5 times upper reference limit value.
Conclusions
The ECG is abnormal in almost all critically ill COVID-19 patients and shows a large spectrum of abnormalities, with signs of acute RVPO in 30% of the patients. Rapid and simple identification of these cases with ECG at hospital admission can facilitate classification of the patients and provide pathophysiological insights.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: [email protected]

Europace: 22 Dec 2020; 22:1848-1854
Bertini M, Ferrari R, Guardigli G, Malagù M, ... Aschieri D, Rapezzi C
Europace: 22 Dec 2020; 22:1848-1854 | PMID: 32944767
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Impact:
Abstract

Frequency of injuries associated with syncope in the prevention of syncope trials.

Jorge JG, Pournazari P, Raj SR, Maxey C, Sheldon RS
Aims
Syncope can lead to injuries. We determined the frequency, severity, and predictors of injuries due to syncope in cohorts of syncope patients.
Methods and results
Participants were enrolled in the POST2 (fludrocortisone) and POST4 (midodrine) vasovagal syncope (VVS) randomized trials, and POST3 enrolled patients with bifascicular block and syncope. Injury was defined as minor (bruising, abrasions), moderate (lacerations), and severe (fractures, burns, joint pain), and recorded up to 1 year after enrolment. A total of 459 patients (median 39 years) were analysed. There were 710 faints occurred in 186 patients during a 1-year follow-up. Fully 56/186 (30%) of patients were injured with syncope (12% of overall group). There were 102 injuries associated with the 710 faints (14%), of which 19% were moderate or severe injuries. Neither patient age, sex, nor the presence of prodromal symptoms associated with injury-free survival. Patients with bifascicular block were more prone to injury (relative risk 1.98, P = 0.018). Patients with ≥4 faints in the prior year had more injuries than those with fewer faints (relative risk 2.97, P < 0.0001), but this was due to more frequent syncope, and not more injuries per faint. In VVS patients, pharmacological therapy significantly reduced the likelihood of an injury due to a syncopal spell (relative risk 0.64, P = 0.015). Injury severity did not associate with age, sex, or prior-year syncope frequency.
Conclusion
Injuries are frequent in syncope patients, but only 4% of injuries were severe. None of age, sex, and prodromal symptoms associate with injury.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: [email protected]

Europace: 22 Dec 2020; 22:1896-1903
Jorge JG, Pournazari P, Raj SR, Maxey C, Sheldon RS
Europace: 22 Dec 2020; 22:1896-1903 | PMID: 32954415
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Impact:
Abstract

Arrhythmic safety of hydroxychloroquine in COVID-19 patients from different clinical settings.

Gasperetti A, Biffi M, Duru F, Schiavone M, ... Tondo C, Forleo GB
Aims
The aim of the study was to describe ECG modifications and arrhythmic events in COVID-19 patients undergoing hydroxychloroquine (HCQ) therapy in different clinical settings.
Methods and results
COVID-19 patients at seven institutions receiving HCQ therapy from whom a baseline and at least one ECG at 48+ h were available were enrolled in the study. QT/QTc prolongation, QT-associated and QT-independent arrhythmic events, arrhythmic mortality, and overall mortality during HCQ therapy were assessed. A total of 649 COVID-19 patients (61.9 ± 18.7 years, 46.1% males) were enrolled. HCQ therapy was administrated as a home therapy regimen in 126 (19.4%) patients, and as an in-hospital-treatment to 495 (76.3%) hospitalized and 28 (4.3%) intensive care unit (ICU) patients. At 36-72 and at 96+ h after the first HCQ dose, 358 and 404 ECGs were obtained, respectively. A significant QT/QTc interval prolongation was observed (P < 0.001), but the magnitude of the increase was modest [+13 (9-16) ms]. Baseline QT/QTc length and presence of fever (P = 0.001) at admission represented the most important determinants of QT/QTc prolongation. No arrhythmic-related deaths were reported. The overall major ventricular arrhythmia rate was low (1.1%), with all events found not to be related to QT or HCQ therapy at a centralized event evaluation. No differences in QT/QTc prolongation and QT-related arrhythmias were observed across different clinical settings, with non-QT-related arrhythmias being more common in the intensive care setting.
Conclusion
HCQ administration is safe for a short-term treatment for patients with COVID-19 infection regardless of the clinical setting of delivery, causing only modest QTc prolongation and no directly attributable arrhythmic deaths.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: [email protected]

Europace: 22 Dec 2020; 22:1855-1863
Gasperetti A, Biffi M, Duru F, Schiavone M, ... Tondo C, Forleo GB
Europace: 22 Dec 2020; 22:1855-1863 | PMID: 32971536
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Abstract

A unified theory for the circuit of atrioventricular nodal re-entrant tachycardia.

Katritsis DG

Atrioventricular nodal re-entrant tachycardia (AVNRT) is the most common regular tachycardia in the human, but its exact circuit remains elusive. In this article, recent evidence about the electrophysiological characteristics of AVNRT and new data on the anatomy of the atrioventricular node, are discussed. Based on this information, a novel, unified theory for the nature of the circuit of the tachycardia is presented.

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Europace: 22 Dec 2020; 22:1763-1767
Katritsis DG
Europace: 22 Dec 2020; 22:1763-1767 | PMID: 32978626
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Impact:
Abstract

Management of ventricular electrical storm: a contemporary appraisal.

Kowlgi GN, Cha YM

Ventricular electrical storm (VES) is a clinical scenario characterized by the clustering of multiple episodes of sustained ventricular arrhythmias (VA) over a short duration. Patients with VES are prone to psychological disorders, heart failure decompensation, and increased mortality. Studies have shown that 10-28% of the patients with secondary prevention ICDs can sustain VES. The triad of a susceptible electrophysiologic substrate, triggers, and autonomic dysregulation govern the pathogenesis of VES. The rate of VA, underlying ventricular function, and the presence of implantable cardioverter-defibrillator (ICD) determine the clinical presentation. A multi-faceted approach is often required for management consisting of acute hemodynamic stabilization, ICD reprogramming when appropriate, antiarrhythmic drug therapy, and sedation. Some patients may be eligible for catheter ablation, and autonomic modulation with thoracic epidural anesthesia, stellate ganglion block, or cardiac sympathetic denervation. Hemodynamically unstable patients may benefit from the use of left ventricular assist devices, and extracorporeal membrane oxygenation. Special scenarios such as idiopathic ventricular fibrillation, Brugada syndrome, Long and short QT syndrome, early repolarization syndrome, catecholaminergic polymorphic ventricular tachycardia, arrhythmogenic right ventricular cardiomyopathy, and cardiac sarcoidosis have been described as well. VES is a cardiac emergency that requires swift intervention. It is associated with poor short and long-term outcomes. A structured team-based management approach is paramount for the safe and effective treatment of this sick cohort.

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Europace: 22 Dec 2020; 22:1768-1780
Kowlgi GN, Cha YM
Europace: 22 Dec 2020; 22:1768-1780 | PMID: 32984880
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Impact:
Abstract

Screening for atrial fibrillation: predicted sensitivity of short, intermittent electrocardiogram recordings in an asymptomatic at-risk population.

Quer G, Freedman B, Steinhubl SR
Aims
Screening for asymptomatic atrial fibrillation (AF) could prevent strokes and save lives, but the AF burden of those detected can impact prognosis. New technologies enable continuous monitoring or intermittent electrocardiogram (ECG) snapshots, however, the relationship between AF detection rates and the burden of AF found with intermittent strategies is unknown. We simulated the likelihood of detecting AF using real-world 2-week continuous ECG recordings and developed a generalizable model for AF detection strategies.
Methods and results
From 1738 asymptomatic screened individuals, ECG data of 69 individuals (mean age 76.3, median burden 1.9%) with new AF found during 14 days continuous monitoring were used to simulate 30 seconds ECG snapshots one to four times daily for 14 days. Based on this simulation, 35-66% of individuals with AF would be detected using intermittent screening. Twice-daily snapshots for 2 weeks missed 48% of those detected by continuous monitoring, but mean burden was 0.68% vs. 4% in those detected (P < 0.001). In a cohort of 6235 patients (mean age 69.2, median burden 4.6%) with paroxysmal AF during clinically indicated monitoring, simulated detection rates were 53-76%. The Markovian model of AF detection using mean episode duration and mean burden simulated actual AF detection with ≤9% error across the range of screening frequencies and durations.
Conclusion
Using twice-daily ECG snapshots over 2 weeks would detect only half of individuals discovered to have AF by continuous recordings, but AF burden of those missed was low. A model predicting AF detection, validated using real-world data, could assist development of optimized AF screening programmes.

© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.

Europace: 22 Dec 2020; 22:1781-1787
Quer G, Freedman B, Steinhubl SR
Europace: 22 Dec 2020; 22:1781-1787 | PMID: 32995870
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Impact:
Abstract

Electrophysiology in the time of coronavirus: coping with the great wave.

Li J, Mazzone P, Leung LWM, Lin W, ... Lin J, Gallagher MM
Aims 
To chart the effect of the COVID-19 pandemic on the activity of interventional electrophysiology services in affected regions.
Methods and results 
We reviewed the electrophysiology laboratory records in three affected cities: Wenzhou in China, Milan in Italy, and London in the UK. We inspected catheter lab records and interviewed electrophysiologists in each centre to gather information on the impact of the pandemic on working patterns and on the health of staff members and patients. There was a striking decline in interventional electrophysiology activity in each of the centres. The decline occurred within a week of the recognition of widespread community transmission of the virus in each region and shows a striking correlation with the national figures for new diagnoses of COVID-19 in each case. During the period of restriction, workflow dropped to <5% of normal, consisting of emergency cases only. In two of three centres, electrophysiologists were redeployed to perform emergency work outside electrophysiology. Among the centres studied, only Wenzhou has seen a recovery from the restrictions in activity. Following an intense nationwide programme of public health interventions, local transmission of COVID-19 ceased to be detectable after 18 February allowing the electrophysiology service to resume with a strict testing regime for all patients.
Conclusion 
Interventional electrophysiology is vulnerable to closure in times of great social difficulty including the COVID-19 pandemic. Intense public health intervention can permit suppression of local disease transmission allowing resumption of some normal activity with stringent precautions.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: [email protected]

Europace: 22 Dec 2020; 22:1841-1847
Li J, Mazzone P, Leung LWM, Lin W, ... Lin J, Gallagher MM
Europace: 22 Dec 2020; 22:1841-1847 | PMID: 32995866
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Impact:
Abstract

Late gadolinium enhancement role in arrhythmic risk stratification of patients with LMNA cardiomyopathy: results from a long-term follow-up multicentre study.

Peretto G, Barison A, Forleo C, Di Resta C, ... Della Bella P, Sala S
Aims
We aimed at addressing the role of late gadolinium enhancement (LGE) in arrhythmic risk stratification of LMNA-associated cardiomyopathy (CMP).
Methods and results
We present data from a multicentre national cohort of patients with LMNA mutations. Of 164 screened cases, we finally enrolled patients with baseline cardiac magnetic resonance (CMR) including LGE sequences [n = 41, age 35 ± 17 years, 51% males, mean left ventricular ejection fraction (LVEF) by echocardiogram 56%]. The primary endpoint of the study was follow-up (FU) occurrence of malignant ventricular arrhythmias [MVA, including sustained ventricular tachycardia (VT), ventricular fibrillation, and appropriate implantable cardioverter-defibrillator (ICD) therapy]. At baseline CMR, 25 subjects (61%) had LGE, with non-ischaemic pattern in all of the cases. Overall, 23 patients (56%) underwent ICD implant. By 10 ± 3 years FU, eight patients (20%) experienced MVA, consisting of appropriate ICD shocks in all of the cases. In particular, the occurrence of MVA in LGE+ vs. LGE- groups was 8/25 vs. 0/16 (P = 0.014). Of note, no significant differences between LGE+ and LGE- patients were found in currently recognized risk factors for sudden cardiac death (male gender, non-missense mutations, baseline LVEF <45% and non-sustained VT), all P-value >0.05.
Conclusions
In LMNA-CMP patients, LGE at baseline CMR is significantly associated with MVA. In particular, as suggested by this preliminary experience, the absence of LGE allowed to rule-out MVA at 10 years mean FU.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: [email protected]

Europace: 22 Dec 2020; 22:1864-1872
Peretto G, Barison A, Forleo C, Di Resta C, ... Della Bella P, Sala S
Europace: 22 Dec 2020; 22:1864-1872 | PMID: 32995851
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Impact:
Abstract

Predictive role of early recurrence of atrial fibrillation after cryoballoon ablation.

Stabile G, Iacopino S, Verlato R, Arena G, ... Landolina M, Tondo C
Aims
The aims of this study were to determine the rate and the predictors of early recurrences of atrial fibrillation (ERAF) after cryoballoon (CB) ablation and to evaluate whether ERAF correlate with the long-term outcome.
Methods and results
Three thousand, six hundred, and eighty-one consecutive patients (59.9 ± 10.5 years, female 26.5%, and 74.3% paroxysmal AF) were included in the analysis. Atrial fibrillation recurrence, lasting at least 30 s, was collected during and after the 3-month blanking period. Three-hundred and sixteen patients (8.6%) (Group A) had ERAF during the blanking period, and 3365 patients (Group B) had no ERAF. Persistent AF and number of tested anti-arrhythmic drugs ≥2 resulted as significant predictors of ERAF. After a mean follow-up of 16.8 ± 16.4 months, 923/3681 (25%) patients had at least one AF recurrence. The observed freedom from AF recurrence, at 24-month follow-up from procedure, was 25.7% and 64.8% in Groups A and B, respectively (P < 0.001). ERAF, persistent AF, and number of tested anti-arrhythmic drugs ≥2 resulted as significant predictors of AF. In a propensity score matching, the logistic model showed that ERAF 1 month after ablation are the best predictor of long-term AF recurrence (P = 0.042).
Conclusion
In patients undergoing CB ablation for AF, ERAF are rare and are a strong predictor of AF recurrence in the follow-up, above all when occur >30 days after the ablation.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: [email protected]

Europace: 22 Dec 2020; 22:1798-1804
Stabile G, Iacopino S, Verlato R, Arena G, ... Landolina M, Tondo C
Europace: 22 Dec 2020; 22:1798-1804 | PMID: 33006599
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Impact:
Abstract

Incidence, characteristics, determinants, and prognostic impact of recurrent syncope.

Zimmermann T, du Fay de Lavallaz J, Nestelberger T, Gualandro DM, ... Lohrmann J, Mueller C
Aims 
The aim of this study is to characterize recurrent syncope, including sex-specific aspects, and its impact on death and major adverse cardiovascular events (MACE).
Methods and results
We characterized recurrent syncope in a large international multicentre study, enrolling patients ≥40 years presenting to the emergency department (ED) with a syncopal event within the last 12 h. Syncope aetiology was centrally adjudicated by two independent cardiologists using all information becoming available during syncope work-up and long-term follow-up. Overall, 1790 patients were eligible for this analysis. Incidence of recurrent syncope was 20% [95% confidence interval (CI) 18-22%] within the first 24 months. Patients with an adjudicated final diagnosis of cardiac syncope (hazard ratio (HR) 1.50, 95% CI 1.11-2.01) or syncope with an unknown aetiology even after central adjudication (HR 2.11, 95% CI 1.54-2.89) had an increased risk for syncope recurrence. Least Absolute Shrinkage and Selection Operator regression fit on all patient information available early in the ED identified >3 previous episodes of syncope as the only independent predictor for recurrent syncope (HR 2.13, 95% CI 1.64-2.75). Recurrent syncope carried an increased risk for death (HR 1.87, 95% CI 1.26-2.77) and MACE (HR 2.69, 95% CI 2.02-3.59) over 24 months of follow-up, however, with a time-dependent effect. These findings were confirmed in a sensitivity analysis excluding patients with syncope recurrence or MACE before or during ED evaluation.
Conclusion 
Recurrence rates of syncope are substantial and vary depending on syncope aetiology. Importantly, recurrent syncope carries a time-dependent increased risk for death and MACE.
Trial registration
BAsel Syncope EvaLuation (BASEL IX, ClinicalTrials.gov registry number NCT01548352).

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: [email protected]

Europace: 22 Dec 2020; 22:1885-1895
Zimmermann T, du Fay de Lavallaz J, Nestelberger T, Gualandro DM, ... Lohrmann J, Mueller C
Europace: 22 Dec 2020; 22:1885-1895 | PMID: 33038231
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Impact:
Abstract

Self-reported treatment burden in patients with atrial fibrillation: quantification, major determinants, and implications for integrated holistic management of the arrhythmia.

Potpara TS, Mihajlovic M, Zec N, Marinkovic M, ... Mujovic N, Stankovic GR
Aims 
Treatment burden (TB) refers to self-perceived cumulative work patients do to manage their health. Using validated tools, TB has been documented in several chronic conditions, but not atrial fibrillation (AF). We measured TB and analysed its determinants and impact on quality of life (QoL) in an AF cohort.
Methods and results 
A single-centre study prospectively included consecutive adult AF patients and non-AF controls managed from 1 April to 21 June 2019, who voluntarily and anonymously answered the TB questionnaire (TBQ) and 5-item EQ-5D QoL questionnaire; TB was calculated as a sum of TBQ points (maximum 170) and expressed as proportion of the maximum value. Of 514 participants, 331 (64.4%) had AF. The mean self-reported TB was 27.6% among AF patients and 24.3% among controls, P = 0.011. The mean TB was significantly higher in patients taking vitamin K antagonists (VKAs) vs. those taking non-VKA antagonist oral anticoagulants (NOAC; 29.5% vs. 24.7%, P = 0.006). The highest item-specific TB was reported for healthcare system organization-related items (e.g. visit appointment), diet, and physical activity modifications. On multivariable analyses, female sex, younger age, and permanent AF were associated with a higher TB, whereas NOACs and electrical AF cardioversion exhibited an inverse association; TB was an independent predictor of decreased QoL (all P < 0.05).
Conclusion 
Our study provided clinically relevant insights into self-perceived TB among AF patients. Approximately one in four patients with AF have a high TB. Specific AF treatments and optimization of healthcare system-required patient activities may reduce the self-perceived TB in AF patients.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: [email protected]

Europace: 22 Dec 2020; 22:1788-1797
Potpara TS, Mihajlovic M, Zec N, Marinkovic M, ... Mujovic N, Stankovic GR
Europace: 22 Dec 2020; 22:1788-1797 | PMID: 33038228
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Impact:
Abstract

Magnetic resonance-guided re-ablation for atrial fibrillation is associated with a lower recurrence rate: a case-control study.

Quinto L, Cozzari J, Benito E, Alarcón F, ... Guasch E, Mont L
Aims
Our aim was to analyse whether using delayed enhancement cardiac magnetic resonance imaging (DE-CMR) to localize veno-atrial gaps in atrial fibrillation (AF) redo ablation procedures improves outcomes during follow-up.
Methods and results
We conducted a case-control study with 35 consecutive patients undergoing a DE-CMR-guided Repeat-pulmonary vein isolation (Re-PVI) procedure. Those with more extensive ablations (e.g. roof lines, box) were excluded. Patients were matched for age, sex, AF pattern, and left atrial dimension with 35 patients who had undergone a conventional Re-PVI procedure guided with a three dimensional (3D)-navigation system. Procedural characteristics were recorded, and patients were followed for 24 months in a specialized outpatient clinic. The primary endpoint was freedom from recurrent AF, atrial tachycardia, or flutter. The duration of CMR-guided procedures was shorter compared to the conventional group (161 ± 52 vs. 195 ± 72 min, respectively, P = 0.049), with no significant differences in fluoroscopy or total radiofrequency time. At the 2-year follow-up, more patients in the DE-CMR-guided group remained free from recurrences compared with the conventional group (70% vs. 39%, respectively, P = 0.007). In univariate Cox-regression analyses, AF pattern [persistent AF, hazard ratio (HR) 2.66 (1.27-5.46), P = 0.006] and the use of DE-CMR [HR 0.36 (0.17-0.79), P = 0.009] predicted recurrences during follow-up; both factors remained independent predictors in multivariate analyses.
Conclusion
The substrate characterization provided by DE-CMR facilitates the identification of anatomical veno-atrial gaps and associates with shorter procedures and better clinical outcomes in repeated AF ablation procedures.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: [email protected]

Europace: 22 Dec 2020; 22:1805-1811
Quinto L, Cozzari J, Benito E, Alarcón F, ... Guasch E, Mont L
Europace: 22 Dec 2020; 22:1805-1811 | PMID: 33063124
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Impact:
Abstract

Anxiety and depression symptoms in Danish patients with an implantable cardioverter-defibrillator: prevalence and association with indication and sex up to 2 years of follow-up (data from the national DEFIB-WOMEN study).

Frydensberg VS, Johansen JB, Möller S, Riahi S, ... Nielsen JC, Pedersen SS
Aims
To investigate (i) the prevalence of anxiety and depression and (ii) the association between indication for implantable cardioverter-defibrillator (ICD) implantation and sex in relation to anxiety and depression up to 24 months\' follow-up.
Methods and results
Patients with a first-time ICD, participating in the national, multi-centre, prospective DEFIB-WOMEN study (n = 1496; 18% women) completed the Hospital Anxiety and Depression Scale at baseline, 3, 6, 12, and 24 months. Data were analysed using linear mixed modelling for longitudinal data. Patients with a secondary prophylactic indication (SPI) had higher mean anxiety scores than patients with a primary prophylactic indication (PPI) at baseline, 3, and 12 months and higher mean depression scores at all-time points, except at 24 months. Women had higher mean anxiety scores as compared to men at all-time points; however, only higher mean depression scores at baseline. Overall, women with SPI had higher anxiety and depression symptom scores than men with SPI. Symptoms decreased over time in both women and men. From baseline to follow-up, the prevalence of anxiety (score ≥8) was highest in patients with SPI (13.3-20.2%) as compared to patients with PPI (range 10.0-14.7%). The prevalence of depression was stable over the follow-up period in both groups (range 8.5-11.1%).
Conclusion
Patients with a SPI reported higher anxiety and depression scores as compared to patients with PPI. Women reported higher anxiety scores than men, but only higher depression scores at baseline. Women with SPI reported the highest anxiety and depression scores overall.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: [email protected]

Europace: 22 Dec 2020; 22:1830-1840
Frydensberg VS, Johansen JB, Möller S, Riahi S, ... Nielsen JC, Pedersen SS
Europace: 22 Dec 2020; 22:1830-1840 | PMID: 33106878
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Impact:
Abstract

Implantation technique and optimal subcutaneous defibrillator chest position: a PRAETORIAN score-based study.

Francia P, Biffi M, Adduci C, Ottaviano L, ... Valsecchi S, Diemberger I
Aims
The traditional technique for subcutaneous implantable cardioverter-defibrillator (S-ICD) implantation involves three incisions and a subcutaneous pocket. Recently, a two-incision and intermuscular (IM) technique has been adopted. The PRAETORIAN score is a chest radiograph-based tool that predicts S-ICD conversion testing. We assessed whether the S-ICD implantation technique affects optimal position of the defibrillation system according to the PRAETORIAN score.
Methods and results
We analysed consecutive patients undergoing S-ICD implantation. The χ2 test and regression analysis were used to determine the association between the PRAETORIAN score and implantation technique. Two hundred and thirteen patients were enrolled. The S-ICD generator was positioned in an IM pocket in 174 patients (81.7%) and the two-incision approach was adopted in 199 (93.4%). According to the PRAETORIAN score, the risk of conversion failure was classified as low in 198 patients (93.0%), intermediate in 13 (6.1%), and high in 2 (0.9%). Patients undergoing the two-incision and IM technique were more likely to have a low (<90) PRAETORIAN score than those undergoing the three-incision and subcutaneous technique (two-incision: 94.0% vs. three-incision: 78.6%; P = 0.004 and IM: 96.0% vs. subcutaneous: 79.5%; P = 0.001). Intermuscular plus two-incision technique was associated with a low-risk PRAETORIAN score (hazard ratio 3.76; 95% confidence interval 1.01-14.02; P = 0.04). Shock impedance was lower in PRAETORIAN low-risk patients than in intermediate-/high-risk categories (66 vs. 96 Ohm; P = 0.001). The PRAETORIAN score did not predict shock failure at 65 J.
Conclusion
In this cohort of S-ICD recipients, combining the two-incision technique and IM generator implantation yielded the lowest PRAETORIAN score values, indicating optimal defibrillation system position.
Clinical trial registration
http://clinicaltrials.gov/ Identifier: NCT02275637.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: [email protected]

Europace: 22 Dec 2020; 22:1822-1829
Francia P, Biffi M, Adduci C, Ottaviano L, ... Valsecchi S, Diemberger I
Europace: 22 Dec 2020; 22:1822-1829 | PMID: 33118017
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Impact:
Abstract

Diagnosis, family screening, and treatment of inherited arrhythmogenic diseases in Europe: results of the European Heart Rhythm Association Survey.

Conte G, Scherr D, Lenarczyk R, Gandjbachkh E, ... Wilde A, Potpara T

The spectrum of inherited arrhythmogenic diseases (IADs) includes disorders without overt structural abnormalities (i.e. primary inherited arrhythmia syndromes) and structural heart diseases (i.e. arrhythmogenic ventricular cardiomyopathy, hypertrophic cardiomyopathy). The aim of this European Heart Rhythm Association (EHRA) survey was to evaluate current clinical practice and adherence to 2015 European Society of Cardiology Guidelines regarding the management of patients with IADs. A 24-item centre-based online questionnaire was presented to the EHRA Research Network Centres and the European Cardiac Arrhythmia Genetics Focus Group members. There were 46 responses from 20 different countries. The survey revealed that 37% of centres did not have any dedicated unit focusing on patients with IADs. Provocative drug challenges were widely used to rule-out Brugada syndrome (BrS) (91% of centres), while they were used in a minority of centres during the diagnostic assessment of long-QT syndrome (11%), early repolarization syndrome (12%), or catecholaminergic polymorphic ventricular tachycardia (18%). While all centres advised family clinical screening with electrocardiograms for all first-degree family members of patients with IADs, genetic testing was advised in family members of probands with positive genetic testing by 33% of centres. Sudden cardiac death risk stratification was straightforward and in line with current guidelines for hypertrophic cardiomyopathy, while it was controversial for other diseases (i.e. BrS). Finally, indications for ventricular mapping and ablation procedures in BrS were variable and not in agreement with current guidelines in up to 54% of centres.

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Europace: 22 Dec 2020; 22:1904-1910
Conte G, Scherr D, Lenarczyk R, Gandjbachkh E, ... Wilde A, Potpara T
Europace: 22 Dec 2020; 22:1904-1910 | PMID: 33367591
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Impact:
Abstract

Atrial fibrillation burden: an update-the need for a CHA2DS2-VASc-AFBurden score.

Tiver KD, Quah J, Lahiri A, Ganesan AN, McGavigan AD

Atrial fibrillation (AF) is an established independent risk factor for stroke. Current guidelines regard AF as binary; either present or absent, with the decision for anti-coagulation driven by clinical variables alone. However, there are increasing data to support a biological gradient of AF burden and stroke risk, both in clinical and non-clinical AF phenotypes. As such, this raises the concept of combining AF burden assessment with a clinical risk score to refine and individualize the assessment of stroke risk in AF-the CHA2DS2VASc-AFBurden score. We review the published data supporting a biological gradient to try and construct a putative schema of risk attributable to AF burden.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: [email protected]

Europace: 21 Dec 2020; epub ahead of print
Tiver KD, Quah J, Lahiri A, Ganesan AN, McGavigan AD
Europace: 21 Dec 2020; epub ahead of print | PMID: 33351904
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Abstract

Focal Impulse and Rotor Modulation Ablation vs. Pulmonary Vein isolation for the treatment of paroxysmal Atrial Fibrillation: results from the FIRMAP AF study.

Tilz RR, Lenz C, Sommer P, Roza MS, ... Vogler J, Eitel C
Aims
Pulmonary vein isolation (PVI) is the gold standard for atrial fibrillation (AF) ablation. Recently, catheter ablation targeting rotors or focal sources has been developed for treatment of AF. This study sought to compare the safety and effectiveness of Focal Impulse and Rotor Modulation (FIRM)-guided ablation as the sole ablative strategy with PVI in patients with paroxysmal AF.
Methods and results
We conducted a multicentre, randomized trial to determine whether FIRM-guided radiofrequency ablation without PVI (FIRM group) was non-inferior to PVI (PVI group) for treatment of paroxysmal AF. The two primary efficacy end points were (i) acute success defined as elimination of AF rotors (FIRM group) or isolation of all pulmonary veins (PVI group) and (ii) long-term success defined as single-procedure freedom from AF/atrial tachycardia (AT) recurrence 12 months after ablation. The study was closed early by the sponsor. At the time of study closure, any pending follow-up visits were waived. A total of 51 patients (mean age 63 ± 10.6 years, 57% male) were enrolled. All PVs were successfully isolated in the PVI group and all rotors were successfully eliminated in the FIRM group. Single-procedure effectiveness was 31.3% (5/16) in the FIRM group and 80% (8/10) in the PVI group at 12 months. Three vascular access complications occurred in the FIRM group.
Conclusion
These partial study effectiveness results reinforce the importance of PVI in paroxysmal AF patients and indicate that FIRM-guided ablation alone (without PVI) is not an effective strategy for treatment of paroxysmal AF in most patients.

© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.

Europace: 21 Dec 2020; epub ahead of print
Tilz RR, Lenz C, Sommer P, Roza MS, ... Vogler J, Eitel C
Europace: 21 Dec 2020; epub ahead of print | PMID: 33351076
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Abstract

Progressive involvement of cardiac conduction system in paediatric patients with Kearns-Sayre syndrome: how to predict occurrence of complete heart block and sudden cardiac death?

Di Mambro C, Tamborrino PP, Silvetti MS, Yammine ML, ... Vici CD, Drago F
Aims
The aims of this study are to evaluate the progressive involvement of the cardiac conduction system in the Kearn-Sayre syndrome (KSS) and to establish criteria for the prevention of episodes of syncope or sudden cardiac death.
Methods and results
This is a prospective monocentric study including KSS patients, with diagnosis based on clinical manifestations, muscle biopsy, and genetic tests, before the age of 18. All patients underwent cardiac screening examination with 12-lead electrocardiogram (ECG), 24-h Holter monitoring, and pacemaker (PM) interrogation twice a year. Fifteen patients (nine males, mean age 16.6 ± 3.9 years) with a sporadic KSS were recruited. All subjects manifested at least one of the intraventricular conduction defects (IVDs): 1 right bundle branch block (RBBB), 2 left anterior fascicular block (LAFB), 11 a bi-fascicular block (RBBB + LAFB), and 1 left posterior fascicular block. Most children with bi-fascicular block developed LAFB before the RBBB (P = 0.0049). In six patients, IVD degenerated into atrioventricular block (AVB). Endocavitary PM was implanted in 11 patients (6 with AVB and 5 with a bi-fascicular block), while an implantable cardioverter-defibrillator only in one patient with a non-sustained ventricular tachycardia. Four died at mean age of 14.7 ± 2.6 years, but none of them suddenly.
Conclusion
Even a \'simple\' ECG can predict the arrhythmic risk and the occurrence of catastrophic events in young patients with KSS. Left anterior fascicular block precedes RBBB in determining the bi-fascicular block and this can predict an inexorable progression of the conduction defects even in a short time. Pacemaker implantation may be indicated in these patients since the first bi-fascicular block manifestation.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: [email protected]

Europace: 17 Dec 2020; epub ahead of print
Di Mambro C, Tamborrino PP, Silvetti MS, Yammine ML, ... Vici CD, Drago F
Europace: 17 Dec 2020; epub ahead of print | PMID: 33336258
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Abstract

Catheter ablation or medical therapy to delay progression of atrial fibrillation: the randomized controlled atrial fibrillation progression trial (ATTEST).

Kuck KH, Lebedev DS, Mikhaylov EN, Romanov A, ... Willems S, Ouyang F
Aims
Delay of progression from paroxysmal to persistent atrial fibrillation (AF) is an important measure of long-term success of AF treatment. However, published data on the impact of catheter ablation on AF progression are limited. This study evaluates whether radiofrequency (RF) catheter ablation delays the progression of AF compared with antiarrhythmic drug (AAD) treatment using current AF management guidelines.
Methods
This prospective, randomized, controlled, two-arm, open-label trial was conducted at 29 hospitals and medical centres across 13 countries. Patients were randomized 1 : 1 to RF ablation or AAD treatment. The primary endpoint was the rate of persistent AF/atrial tachycardia (AT) at 3 years.
Results
After early study termination following slow enrolment, 255 (79%) of the planned 322 patients were enrolled (RF ablation, n = 128, AAD, n = 127); 36% of patients in the RF ablation group and 41% in the AAD group completed 3 years of follow-up. For the primary endpoint, the Kaplan-Meier estimate of the rate of persistent AF/AT at 3 years was significantly lower with RF ablation [2.4% (95% confidence interval (CI), 0.6-9.4%)] than with AAD therapy [17.5% (95% CI, 10.7-27.9%); one-sided P = 0.0009]. Patients ≥65 years were ∼4 times more likely to progress to persistent AF/AT than patients <65 years, suggesting RF ablation can delay disease progression [hazard ratio: 3.87 (95% CI, 0.88-17.00); P = 0.0727]. Primary adverse events were reported for eight patients in the RF ablation group.
Conclusions
Radiofrequency ablation is superior to guideline-directed AAD therapy in delaying the progression from paroxysmal to persistent AF.

© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.

Europace: 16 Dec 2020; epub ahead of print
Kuck KH, Lebedev DS, Mikhaylov EN, Romanov A, ... Willems S, Ouyang F
Europace: 16 Dec 2020; epub ahead of print | PMID: 33330909
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Abstract

Two siblings with early repolarization syndrome: clinical and genetic characterization by whole-exome sequencing.

Steinfurt J, Bezzina CR, Biermann J, Staudacher D, ... Odening KE, Lodder EM
Aims 
The early repolarization syndrome (ERS) can cause ventricular fibrillation (VF) and sudden death in young, otherwise healthy individuals. There are limited data suggesting that ERS might be heritable. The aim of this study was to characterize the clinical phenotype and to identify a causal variant in an affected family using an exome-sequencing approach.
Methods and results 
Early repolarization syndrome was diagnosed according to the recently proposed Shanghai ERS Score. After sequencing of known ERS candidate genes, whole-exome sequencing (WES) was performed. The index patient (23 years, female) showed a dynamic inferolateral early repolarization (ER) pattern and electrical storm with intractable VF. Isoproterenol enabled successful termination of electrical storm with no recurrence on hydroquinidine therapy during 33 months of follow-up. The index patient\'s brother (25 years) had a persistent inferior ER pattern with malignant features and a history of syncope. Both parents were asymptomatic and showed no ER pattern. While there was no pathogenic variant in candidate genes, WES detected a novel missense variant affecting a highly conserved residue (p. H2245R) in the ANK3 gene encoding Ankyrin-G in the two siblings and the father.
Conclusion 
We identified two siblings with a malignant ERS phenotype sharing a novel ANK3 variant. A potentially pathogenic role of the novel ANK3 variant is suggested by the direct interaction of Ankyrin-G with the cardiac sodium channel, however, more patients with ANK3 variants and ERS would be required to establish ANK3 as novel ERS susceptibility gene. Our study provides additional evidence that ERS might be a heritable condition.

© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.

Europace: 15 Dec 2020; epub ahead of print
Steinfurt J, Bezzina CR, Biermann J, Staudacher D, ... Odening KE, Lodder EM
Europace: 15 Dec 2020; epub ahead of print | PMID: 33324992
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Abstract

Efficacy and safety of left atrial appendage electrical isolation during catheter ablation of atrial fibrillation: an updated meta-analysis.

Romero J, Gabr M, Patel K, Briceno D, ... Natale A, Di Biase L
Aims
Left atrial appendage electrical isolation (LAAEI) has been shown to improve freedom from all-atrial arrhythmia recurrence in patients with non-paroxysmal atrial fibrillation (AF). The aim of this study is to investigate the long-term efficacy and safety outcomes of LAAEI in patients with non-paroxysmal AF undergoing catheter ablation.
Methods and results
A systematic review of Medline, Cochrane, and Embase was performed for clinical studies evaluating the benefit of LAAEI in non-paroxysmal AF. Nine studies with a total of 2336 patients were included (mean age: 65 ± 9 years, 63% male). All studies included patients with persistent AF, long-standing persistent AF, or both. At a mean follow-up of 40.5 months, patients who underwent LAAEI had significantly higher freedom from all-atrial arrhythmia recurrence than patients who underwent standard ablation alone [69.3% vs. 46.4%; risk ratio (RR) 0.54; 95% confidence interval (CI) 0.42-0.69; P < 0.0001]. A 46% relative risk reduction and 22.9% absolute risk reduction in atrial-arrhythmia recurrence was noted with LAAEI. Rates of cerebral thromboembolism were not significantly different between the two groups (LAAEI 3% vs. standard ablation 1.6%, respectively; RR 1.76; 95% CI 0.61-5.04; P = 0.29). Furthermore, there was no significant difference in the acute procedural complication rates between the two groups (LAAEI 4% vs. standard ablation 3%, respectively; RR 1.29; 95% CI 0.83-2.02; P = 0.26).
Conclusion
At long-term follow-up, LAAEI led to a significantly higher improvement in freedom from all-atrial arrhythmia recurrence in patients with non-paroxysmal AF, when compared to standard ablation alone. Importantly, this benefit was achieved without an increased risk of acute procedural complications or cerebral thromboembolic events.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: [email protected]

Europace: 15 Dec 2020; epub ahead of print
Romero J, Gabr M, Patel K, Briceno D, ... Natale A, Di Biase L
Europace: 15 Dec 2020; epub ahead of print | PMID: 33324978
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Abstract

Sex-related differences of fatty acid-binding protein 4 and leptin levels in atrial fibrillation.

López-Canoa JN, Couselo-Seijas M, Baluja A, González-Melchor L, ... Eiras S, Rodríguez-Mañero M
Aims
Adiposity plays a key role in the pathogenesis of atrial fibrillation (AF). Our aim was to study the sex differences in adipokines levels according to AF burden.
Methods and results
Two independent cohorts of patients were studied: (i) consecutive patients with AF undergoing catheter ablation (n = 217) and (ii) a control group (n = 105). (i) Adipokines, oxidative stress, indirect autonomic markers, and leucocytes mRNA levels were analysed; (ii) correlation between biomarkers was explored with heatmaps and Kendall correlation coefficients; and (iii) logistic regression and random forest model were used to determine predictors of AF recurrence after ablation. Our results showed that: (i) fatty acid-binding protein 4 (FABP4) and leptin levels were higher in women than in men in both cohorts (P < 0.01). In women, FABP4 levels were higher on AF cohort (20 ± 14 control, 29 ± 18 paroxysmal AF and 31 ± 17 ng/mL persistent AF; P < 0.01). In men, leptin levels were lower on AF cohort (22 ± 15 control, 13 ± 16 paroxysmal AF and 13 ± 11 ng/mL persistent AF; P < 0.01). (ii) In female with paroxysmal AF, there was a lower acetylcholinesterase and higher carbonic anhydrase levels with respect to men (P < 0.05). (iii) Adipokines have an important role on discriminate AF recurrence after ablation. In persistent AF, FABP4 was the best predictor of recurrence after ablation (1.067, 95% confidence interval 1-1.14; P = 0.046).
Conclusion
The major finding of the present study is the sex-based differences of FABP4 and leptin levels according to AF burden. These adipokines are associated with oxidative stress, inflammatory and autonomic indirect markers, indicating that they may play a role in AF perpetuation.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: [email protected]

Europace: 14 Dec 2020; epub ahead of print
López-Canoa JN, Couselo-Seijas M, Baluja A, González-Melchor L, ... Eiras S, Rodríguez-Mañero M
Europace: 14 Dec 2020; epub ahead of print | PMID: 33319222
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Abstract

\'Hot phase\' clinical presentation in arrhythmogenic cardiomyopathy.

Bariani R, Cipriani A, Rizzo S, Celeghin R, ... Perazzolo Marra M, Bauce B
Aims
The aim of this study is to evaluate the clinical features of patients affected by arrhythmogenic cardiomyopathy (AC), presenting with chest pain and myocardial enzyme release in the setting of normal coronary arteries (\'hot phase\').
Methods and results
We collected detailed anamnestic, clinical, instrumental, genetic, and histopathological findings as well as follow-up data in a series of AC patients who experienced a hot phase. A total of 23 subjects (12 males, mean age at the first episode 27 ± 16 years) were identified among 560 AC probands and family members (5%). At first episode, 10 patients (43%) already fulfilled AC diagnostic criteria. Twelve-lead electrocardiogram recorded during symptoms showed ST-segment elevation in 11 patients (48%). Endomyocardial biopsy was performed in 11 patients, 8 of them during the acute phase showing histologic evidence of virus-negative myocarditis in 88%. Cardiac magnetic resonance was performed in 21 patients, 12 of them during the acute phase; oedema and/or hyperaemia were detected in 7 (58%) and late gadolinium enhancement in 11 (92%). At the end of follow-up (mean 17 years, range 1-32), 12 additional patients achieved an AC diagnosis. Genetic testing was positive in 77% of cases and pathogenic mutations in desmoplakin gene were the most frequent. No patient complained of sustained ventricular arrhythmias or died suddenly during the \'hot phase\'.
Conclusion
\'Hot phase\' represents an uncommon clinical presentation of AC, which often occurs in paediatric patients and carriers of desmoplakin gene mutations. Tissue characterization, family history, and genetic test represent fundamental diagnostic tools for differential diagnosis.

© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.

Europace: 12 Dec 2020; epub ahead of print
Bariani R, Cipriani A, Rizzo S, Celeghin R, ... Perazzolo Marra M, Bauce B
Europace: 12 Dec 2020; epub ahead of print | PMID: 33313835
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Abstract

European experience with a first totally leadless cardiac resynchronization therapy pacemaker system.

Carabelli A, Jabeur M, Jacon P, Rinaldi CA, ... Neuzil P, Defaye P
Aims
Totally leadless cardiac resynchronization therapy (CRT) can be delivered with a combination of Micra and WiSE-CRT systems. We describe the technical feasibility and first insights into the safety and efficacy of this combination in European experience.
Methods and results
Patients enrolled had indication for both Micra and WiSE-CRT systems because of heart failure related to high burden of pacing by a Micra necessitating system upgrade or inability to implant a conventional CRT system because of infectious or anatomical conditions. The endpoints of the study were technical success of WiSE-CRT implantation with right ventricle-synchonized CRT delivery, acute QRS duration reduction, and freedom from procedure-related major adverse events. All eight WiSE-CRT devices were able to detect the Micra pacing output and to be trained to deliver synchronous LV endocardial pacing. Acute QRS reduction following WiSE-CRT implantation was observed in all eight patients (mean QRS 204.38 ± 30.26 vs. 137.5 ± 24.75 mS, P = 0.012). Seven patients reached 6 months of follow-up. At 6 months after WiSE-CRT implantation, there was a significant increase in LV ejection fraction (28.43 ± 8.01% vs. 39.71 ± 11.89%; P = 0.018) but no evidence of LV reverse remodelling or improvement in New York Heart Association class.
Conclusion
The Micra and the WiSE-CRT systems can successfully operate together to deliver total leadless CRT to a patient. Moreover, the WiSE-CRT system provides the only means to upgrade the large population of Micra patients to CRT capability without replacing the Micra. The range of application of this combination could broaden in the future with the upcoming developments of leadless cardiac pacing.

© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.

Europace: 12 Dec 2020; epub ahead of print
Carabelli A, Jabeur M, Jacon P, Rinaldi CA, ... Neuzil P, Defaye P
Europace: 12 Dec 2020; epub ahead of print | PMID: 33313789
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Abstract

SETAP: epidemiology and prevention of stroke and transient ischaemic attack in Czech patients with atrial fibrillation.

Táborský M, Dušek L, Kautzner J, Vícha M, ... Bezděková M, Skála T
Aims
The aim of this study is to analyse the prevalence, epidemiology, and anticoagulation prevention of stroke or transient ischaemic attack (TIA) in Czech patients with atrial fibrillation (AF).
Methods and results
Retrospective observational analysis of diagnoses, procedures, and treatment reported to the Czech National Registry of Reimbursed Healthcare Services between 2015 and 2018. Prevalence of AF in 2018 was 4.3% of Czech population and the prevalence of stroke/TIA in AF patients was 22.3% with annual incidence of 181.62 cases per 100 000 inhabitants. In 2018, CHA2DS2-ASc score ≥4 was present in 98% AF patients in secondary and 59% in primary prevention, respectively, while the anticoagulation treatment was used by 71-81% of them. Between 2015 and 2018, the percentage of AF patients treated with warfarin monotherapy in primary prevention decreased from 35% to 31%, with acetylsalicylic acid (ASA) monotherapy from 18% to 16% and non-vitamin K antagonist oral anticoagulants (NOACs) monotherapy increased from 7% to 11%. In secondary prevention, the percentage of warfarin monotherapy treatment decreased from 35% to 32%, with ASA monotherapy from 20% to 18% and with NOACs monotherapy increased from 9% to 15%.
Conclusion
This study followed all Czech patients with AF. The unadjusted prevalence and incidence of AF was higher compared with other countries and 2019 European Society of Cardiology Statistics. The study identified several gaps in standard of reimbursed care. 20-30% of AF patients with other risk factors were without any prevention medication and the share of ASA monotherapy in treated patients was 16-18%.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: [email protected]

Europace: 10 Dec 2020; epub ahead of print
Táborský M, Dušek L, Kautzner J, Vícha M, ... Bezděková M, Skála T
Europace: 10 Dec 2020; epub ahead of print | PMID: 33305813
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Abstract

Prediction of low-voltage areas using modified APPLE score.

Seewöster T, Kosich F, Sommer P, Bertagnolli L, Hindricks G, Kornej J
Aims
The presence of low-voltage areas (LVAs) in patients with atrial fibrillation (AF) reflects left atrial (LA) electroanatomical substrate, which is essential for individualized AF management. However, echocardiographic anteroposterior LA diameter included into previous LVAs prediction scores does not mirror LA size accurately and impaired left ventricular ejection fraction (LV-EF) is not directly associated with atrial myopathy. Therefore, we aimed to compare a modified (m)APPLE score, which included LA volume (LAV) and LA emptying fraction (LA-EF) with the regular APPLE score for the prediction of LVAs.
Methods and results
In patients undergoing first AF catheter ablation, LVAs were determined peri-interventionally using high-density maps and defined as signal amplitude <0.5 mV. All patients underwent cardiovascular magnetic resonance imaging before intervention. The APPLE (one point for Age ≥ 65 years, Persistent AF, imPaired eGFR ≤ 60 mL/min/1.73 m2, LA diameter ≥ 43 mm, and LVEF < 50%) and (m)APPLE (last two variables changed by LAV ≥ 39 mL/m2, and LA-EF < 31%) scores were calculated at baseline. The study population included 219 patients [median age 65 (interquartile range 57-72) years, 41% females, 59% persistent AF, 25% LVAs]. Both scores were significantly associated with LVAs [OR 1.817, 95% CI 1.376-2.399 for APPLE and 2.288, 95% CI 1.650-3.172 for (m)APPLE]. Using receiver operating characteristic curves analysis, the (m)APPLE score [area under the curve (AUC) 0.779, 95% CI 0.702-0.855] showed better LVAs prediction than the APPLE score (AUC 0.704, 95% CI 0.623-0.784), however, without statistically significant difference (P = 0.233).
Conclusion
The modified (m)APPLE score demonstrated good prognostic value for LVAs prediction and was comparable with the regular APPLE score.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: [email protected]

Europace: 05 Dec 2020; epub ahead of print
Seewöster T, Kosich F, Sommer P, Bertagnolli L, Hindricks G, Kornej J
Europace: 05 Dec 2020; epub ahead of print | PMID: 33279992
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Abstract

Comparative data on left atrial appendage occlusion efficacy and clinical outcomes by age group in the Amplatzer™ Amulet™ Occluder Observational Study.

Freixa X, Schmidt B, Mazzone P, Berti S, ... Aminian A, Nielsen-Kudsk JE
Aims
Left atrial appendage occlusion (LAAO) may be considered for patients with non-valvular atrial fibrillation (NVAF) and a relative/formal contraindication to anticoagulation. This study aimed to summarize the impact of aging on LAAO outcomes at short and long-term follow-up.
Methods and results
We compared subjects aged <70, ≥70 and <80, and ≥80 years old in the prospective, multicentre Amplatzer™ Amulet™ Occluder Observational Study (Abbott, Plymouth, MN, USA). Serious adverse events (SAEs) were reported from implant through a 2-year post-LAAO visit and adjudicated by an independent clinical events committee. Overall, 1088 subjects were prospectively enrolled. There were 265 subjects (24.4%) <70 years old, 491 subjects (45.1%) ≥70 and <80 years old, and 332 subjects (30.5%) ≥80 years old, with the majority (≥80%) being contraindicated to anticoagulation. As expected, CHA2DS2-VASc and HAS-BLED Scores increased with age. Implant success was high (≥98.5%) across all groups, and the proportion of subjects with a procedure- or device-related SAE was similar between groups. At follow-up, the observed ischaemic stroke rate was not significantly different between groups, and corresponding risk reductions were 62, 56, and 85% when compared with predicted rates for subjects <70, ≥70 and <80, and ≥80 years old, respectively. Major bleeding and mortality rates increased with age, while the incidence of device-related thrombus tended to increase with age.
Conclusions
Despite the increased risk for ischaemic stroke with increasing age in AF patients, LAAO reduced the risk for ischaemic stroke compared with the predicted rate across all age groups without differences in procedural SAEs.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: [email protected]

Europace: 05 Dec 2020; epub ahead of print
Freixa X, Schmidt B, Mazzone P, Berti S, ... Aminian A, Nielsen-Kudsk JE
Europace: 05 Dec 2020; epub ahead of print | PMID: 33279979
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Abstract

Polyscore of autonomic parameters for risk stratification of the elderly general population: the Polyscore study.

Steger A, Dommasch M, Müller A, Sinnecker D, ... Malik M, Schmidt G
Aims
Present society is constantly ageing and elderly frequently suffer from conditions that are difficult and/or costly to treat if detected late. Effective screening of the elderly is therefore needed so that those requiring detailed clinical work-up are identified early. We present a prospective validation of a screening strategy based on a Polyscore of seven predominantly autonomic, non-invasive risk markers.
Methods and results
Within a population-based survey in Germany (INVADE study), participants aged ≥60 years were enrolled between August 2013 and February 2015. Seven prospectively defined Polyscore components were obtained during 30-min continuous recordings of electrocardiogram, blood pressure, and respiration. Out of 1956 subjects, 168 were excluded due to atrial fibrillation, implanted pacemaker, or unsuitable recordings. All-cause mortality over a median 4-year follow-up was prospectively defined as the primary endpoint. The Polyscore divided the investigated population (n = 1788, median age: 72 years, females: 58%) into three predefined groups with low (n = 1405, 78.6%), intermediate (n = 326, 18.2%), and high risk (n = 57, 3.2%). During the follow-up, 82 (4.6%) participants died. Mortality in the Polyscore-defined risk groups was 3.4%, 7.4%, and 17.5%, respectively (P < 0.0001). The Polyscore-based mortality prediction was independent of Framingham score, diabetes, chronic kidney disease, and major stroke and/or myocardial infarction history. It was particularly effective in those aged <75 years (n = 1145).
Conclusion
The Polyscore-based mortality risk assessment from short-term non-invasive recordings is effective in the elderly general population, especially those aged 60-74 years. Implementation of a comprehensive Polyscore screening of this age group is proposed to advance preventive medical care.

© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.

Europace: 03 Dec 2020; epub ahead of print
Steger A, Dommasch M, Müller A, Sinnecker D, ... Malik M, Schmidt G
Europace: 03 Dec 2020; epub ahead of print | PMID: 33276379
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Abstract

Radiofrequency ablation: technological trends, challenges, and opportunities.

Habibi M, Berger RD, Calkins H

More than three decades have passed since utilization of radiofrequency (RF) ablation in the treatment of cardiac arrhythmias. Although several limitations and challenges still exist, with improvements in catheter designs and delivery of energy the way we do RF ablation now is much safer and more efficient. This review article aims to give an overview on historical advances on RF ablation and challenges in performing safe and efficient ablation.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: [email protected]

Europace: 29 Nov 2020; epub ahead of print
Habibi M, Berger RD, Calkins H
Europace: 29 Nov 2020; epub ahead of print | PMID: 33253390
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Abstract

Impact of electroanatomical mapping-guided lead implantation on procedural outcome of His bundle pacing.

Richter S, Ebert M, Bertagnolli L, Gebauer R, ... Hindricks G, Döring M
Aims
Conventional His bundle pacing (HBP) can be technically challenging and fluoroscopy-intense, particularly in patients with His-Purkinje conduction disease (HPCD). Three-dimensional electroanatomical mapping (EAM) facilitates non-fluoroscopic lead navigation and HB electrogram mapping. We sought to assess the procedural outcome of routine EAM-guided HBP compared with conventional HBP in a real-world population and evaluate the feasibility and safety of EAM-guided HBP in patients with HPCD.
Methods and results 
We included 58 consecutive patients (72 ± 13 years; 71% male) who underwent an attempt to conventional (EAM- group; n = 29) or EAM-guided (EAM+ group; n = 29) HBP between June 2019 and April 2020. The centre\'s learning curve was initially determined (n = 40 cases) to define the conventional control group and minimize outcome bias favouring EAM-guided HBP. His bundle pacing was successful in 26 patients (90%) in the EAM+ and 27 patients (93%) in the EAM- group (P = 0.64). The procedure time was 90 (73-135) and 110 (70-130) min, respectively (P = 0.89). The total fluoroscopy time [0.7 (0.5-1.4) vs. 3.3 (1.4-6.5) min; P < 0.001] and fluoroscopy dose [21.9 (9.1-47.7) vs. 78.6 (27.2-144.9) cGycm2; P = 0.001] were significantly lower in the EAM+ than EAM- group. There were no significant differences between groups in His capture threshold (1.2 ± 0.6 vs. 1.4 ± 1.0 V/1.0 ms; P = 0.33) and paced QRS duration (113 ± 15 vs. 113 ± 17 ms; P = 0.89). In patients with HPCD, paced QRS duration was similar in both groups (121 ± 15 vs. 123 ± 12 ms; P = 0.77). The bundle branch-block recruitment threshold tended to be lower in the EAM+ than EAM- group (1.3 ± 0.7 vs. 1.8 ± 1.2 V/1.0 ms; P = 0.31). No immediate procedure-related complications occurred. One patient (2%) experienced lead dislodgement during 4-week follow-up.
Conclusion 
Implementation of routine EAM-guided HBP lead implantation is feasible and safe in a real-world cohort of patients with and without HPCD and results in a tremendous reduction in radiation exposure without prolonging procedure time or increasing procedure-related complications.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: [email protected]

Europace: 29 Nov 2020; epub ahead of print
Richter S, Ebert M, Bertagnolli L, Gebauer R, ... Hindricks G, Döring M
Europace: 29 Nov 2020; epub ahead of print | PMID: 33253376
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Abstract

FRAGILE: FRench Attitude reGistry in case of ICD LEad replacement.

Alonso C, Marquie C, Defaye P, Clementy N, ... Piot O, Deharo JC
Aims
FRench Attitude reGistry in case of ICD LEad replacement (FRAGILE) registry was set-up to describe the attitude in different French institutions in case of implantable cardioverter-defibrillator (ICD) lead replacement, extraction, or abandonment and to compare outcomes in both groups.
Methods and results
Prospective observational study comparing two attitudes in case of ICD lead replacement, extraction, or abandonment. Primary endpoint describes the attitude in different French centres, collect parameters that may influence the decision. Secondary endpoint compares early and mid-term (2 years) complications in both groups.Between April 2013 and April 2017, 552 patients were included in 32 centres. 434 (78.6%) were male, mean patient\'s age was 60.3 ± 14.4 years. In 56.9% of the cases, the decision was to explant the lead. Patients in the extraction group were younger than in the abandonment group (56.7 ± 14.5 vs. 65 ± 12.7 P < 0.0001) and less likely to have comorbidities (46.5% vs. 58.3% of the patients P = 0.022). The mean lead dwelling time was significantly longer in the abandonment group as compared with the extraction group (7.6 ± 3.9 vs. 5.2 ± 3.1 years, P < 0.0001). There was no statistical difference between both groups concerning early and 2 years complications.
Conclusion
In this registry, the strategy in case of non-infected ICD lead replacement was mainly influenced by patient\'s age and comorbidities and lead dwelling time. No difference was observed in outcomes in both strategies.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: [email protected]

Europace: 29 Nov 2020; epub ahead of print
Alonso C, Marquie C, Defaye P, Clementy N, ... Piot O, Deharo JC
Europace: 29 Nov 2020; epub ahead of print | PMID: 33257986
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Abstract

Wearable cardioverter-defibrillator in patients with a transient risk of Sudden cardiac death: the WEARIT-France cohort study.

Garcia R, Combes N, Defaye P, Narayanan K, ... Leclercq C, Marijon E
Aims 
We aimed to provide contemporary real-world data on wearable cardioverter-defibrillator (WCD) use, not only in terms of effectiveness and safety but also compliance and acceptability.
Methods and results 
Across 88 French centres, the WEARIT-France study enrolled retrospectively patients who used the WCD between May 2014 and December 2016, and prospectively all patients equipped for WCD therapy between January 2017 and March 2018. All patients received systematic education session through a standardized programme across France at the time of initiation of WCD therapy and were systematically enrolled in the LifeVest Network remote services. Overall, 1157 patients were included (mean age 60 ± 12 years, 16% women; 46% prospectively): 82.1% with ischaemic cardiomyopathy, 10.3% after implantable cardioverter-defibrillator explant, and 7.6% before heart transplantation. Median WCD usage period was 62 (37-97) days. Median daily wear time of WCD was 23.4 (22.2-23.8) h. In multivariate analysis, younger age was associated with lower compliance [adjusted odds ratio (OR) 0.97, 95% confidence interval (CI) 0.95-0.99, P < 0.01]. A total of 18 participants (1.6%) received at least one appropriate shock, giving an incidence of appropriate therapy of 7.2 per 100 patient-years. Patient-response button allowed the shock to be aborted in 35.7% of well-tolerated sustained ventricular arrhythmias and in 95.4% of inappropriate ventricular arrhythmia detection, finally resulting in an inappropriate therapy in eight patients (0.7%).
Conclusion
Our real-life findings reinforce previous studies on the efficacy and safety of the WCD in the setting of transient high-risk group in selected patients. Moreover, they emphasize the fact that when prescribed appropriately, in concert with adequate patient education and dedicated follow-up using specific remote monitoring system, compliance with WCD is high and the device well-tolerated by the patient.

© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.

Europace: 29 Nov 2020; epub ahead of print
Garcia R, Combes N, Defaye P, Narayanan K, ... Leclercq C, Marijon E
Europace: 29 Nov 2020; epub ahead of print | PMID: 33257972
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Abstract

Upgrade from implantable cardioverter-defibrillator vs. de novo implantation of cardiac resynchronization therapy: long-term outcomes.

Jędrzejczyk-Patej E, Mazurek M, Kotalczyk A, Kowalska W, ... Średniawa B, Lenarczyk R
Aims 
To assess and compare long-term mortality and predictors thereof in de novo cardiac resynchronization therapy defibrillators (CRT-D) vs. upgrade from an implantable cardioverter-defibrillator (ICD) to CRT-D.
Methods and results 
Study population consisted of 595 consecutive patients with CRT-D implanted between 2002 and 2015 in a tertiary care, university hospital, in a densely inhabited, urban region of Poland [480 subjects (84.3%) with CRT-D de novo implantation; 115 patients (15.7%) upgraded from ICD to CRT-D]. In a median observation of 1692 days (range 457-3067), all-cause mortality for de novo CRT-D vs. CRT-D upgrade was 35.5% vs. 43.5%, respectively (P = 0.045). On multivariable regression analysis including all CRT recipients, the previously implanted ICD was an independent predictor for death [hazard ratio (HR) 1.58, 95% confidence interval (CI) 1.10-2.29, P = 0.02]. For those, who were upgraded from ICD to CRT-D, the independent predictors for all-cause death were as follows: creatinine level (HR 1.01, 95% CI 1.00-1.02, P = 0.01), left ventricular end-systolic diameter (HR 1.07, 95% CI 1.02-1.11, P = 0.002), New York Heart Association (NYHA) IV class at baseline (HR 2.36, 95% CI 1.00-5.53, P = 0.049) and cardiac device-related infective endocarditis during follow-up (HR 2.42, 95% CI 1.02-5.75, P = 0.046). A new CRT scale (Creatinine ≥150 μmol/L; Remodelling, left ventricular end-systolic ≥59 mm; Threshold for NYHA, NYHA = IV) showed high prediction for mortality in CRT-D upgrades (AUC 0.70, 95% CI 0.59-0.80, P = 0.0007).
Conclusion 
All-cause mortality in patients upgraded from ICD is significantly higher compared with de novo CRT-D implantations and reaches almost 45% within 4.5 years. A new CRT scale (Creatinine; Remodelling; Threshold for NYHA) has been proposed to help survival prediction following CRT upgrade.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: [email protected]

Europace: 29 Nov 2020; epub ahead of print
Jędrzejczyk-Patej E, Mazurek M, Kotalczyk A, Kowalska W, ... Średniawa B, Lenarczyk R
Europace: 29 Nov 2020; epub ahead of print | PMID: 33257952
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Abstract

Prevalence and prognostic association of ventricular arrhythmia in non-ischaemic heart failure patients: results from the DANISH trial.

Boas R, Thune JJ, Pehrson S, Køber L, ... Svendsen JH, Dixen U
Aims
Improved risk stratification to identify non-ischaemic heart failure patients who will benefit from primary prophylactic implantable cardioverter-defibrillator (ICD) is needed. We examined the potential of ventricular arrhythmia to identify patients who could benefit from an ICD.
Methods and results
A total of 850 non-ischaemic systolic heart failure patients with left ventricle ≤35% and elevated N-terminal pro-brain natriuretic peptides had a 24-h Holter monitor recording performed. We examined present non-sustained ventricular tachycardia (NSVT), defined as ≥3 consecutive premature ventricular contractions (PVCs) with a rate of ≥100/min, and number of PVCs per hour stratified into low (<30) and high burden (≥30) groups. Outcome measures were overall mortality, sudden cardiac death (SCD), and cardiovascular death (CVD). In total, 193 patients died, 49 from SCD and 125 from CVD. Non-sustained ventricular tachycardia (365 patients) was significantly associated with increased all-cause mortality [hazard ratio (HR) 1.47; 95% confidence interval (CI) 1.07-2.03; P = 0.02] and to CVD (HR 1.89; CI 1.25-2.87; P = 0.003). High burden PVC (352 patients) was associated with increased all-cause mortality (HR1.38; CI 1.00-1.90; P = 0.046) and with CVD (HR 1.78; CI 1.19-2.66; P = 0.005). There was no statistically significant association with SCD for neither NSVT nor PVC. In interaction analyses, neither NSVT (P = 0.56) nor high burden of PVC (P = 0.97) was associated with survival benefit from ICD implantation.
Conclusion
Ventricular arrhythmia in non-ischaemic heart failure patients was associated with a worse prognosis but could not be used to stratify patients to ICD implantation.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: [email protected]

Europace: 29 Nov 2020; epub ahead of print
Boas R, Thune JJ, Pehrson S, Køber L, ... Svendsen JH, Dixen U
Europace: 29 Nov 2020; epub ahead of print | PMID: 33257933
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Abstract

Periprocedural anticoagulation in the uninterrupted edoxaban vs. vitamin K antagonists for ablation of atrial fibrillation (ELIMINATE-AF) trial.

Hohnloser SH, Camm AJ, Cappato R, Diener HC, ... Smolnik R, Kautzner J
Aims 
This post hoc analysis of ELIMINATE-AF evaluated requirements of unfractionated heparin (UFH) and procedure-related bleeding in atrial fibrillation (AF) patients undergoing ablation with uninterrupted edoxaban or vitamin K antagonist (VKA) therapy.
Methods and results 
Patients were randomized 2:1 to once-daily edoxaban 60 mg (or dose-reduced 30 mg) or dose-adjusted VKA (target international normalized ratio: 2.0-3.0). Uninterrupted anticoagulation was mandated for 21-28 days\' pre-ablation and 90 days\' post-ablation. During ablation, UFH administration targeted an activated clotting time (ACT) of 300-400 s. Periprocedural bleeding was differentiated between procedure-related (bleeding at puncture side, cardiac tamponade) and unrelated events. Of 614 randomized patients, 553 received study drug and underwent catheter ablation (edoxaban n = 375; VKA n = 178). The median (Q1-Q3) time from last dose to ablation procedure was 14.8 (13.3-16.5) vs. 16.5 (14.8-19.5) h (edoxaban vs. VKA group, respectively). Mean ACT (SD) ≥300 s was observed in 52% edoxaban- vs. 76% VKA-treated patients, despite a higher mean (SD) UFH dose in the edoxaban vs. VKA group [14 261 (6397) IU vs. 11 473 (4300) IU; exploratory P-value < 0.0001]. In the edoxaban group, 13 patients (3.5%) had procedure-related bleeds of whom 9 had received an UFH dose above the median (13 000 IU). In the VKA arm, 7 patients (3.9%) had procedure-related bleeds of whom 3 had received an UFH dose above the median (10 225 IU).
Conclusion 
The rate of procedure-related major/clinically relevant non-major bleeding did not differ between the treatment arms despite higher doses of UFH used with edoxaban vs. VKA to achieve a target ACT during AF ablation.

© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.

Europace: 28 Nov 2020; epub ahead of print
Hohnloser SH, Camm AJ, Cappato R, Diener HC, ... Smolnik R, Kautzner J
Europace: 28 Nov 2020; epub ahead of print | PMID: 33249467
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Abstract

The evolution of cardiac resynchronization therapy and an introduction to conduction system pacing: a conceptual review.

Herweg B, Welter-Frost A, Vijayaraman P

In chronic systolic heart failure and conduction system disease, cardiac resynchronization therapy (CRT) is the only known non-pharmacologic heart failure therapy that improves cardiac function, functional capacity, and survival while decreasing cardiac workload and hospitalization rates. While conventional bi-ventricular pacing has been shown to benefit patients with heart failure and conduction system disease, there are limitations to its therapeutic success, resulting in widely variable clinical response. Limitations of conventional CRT evolve around myocardial scar, fibrosis, and inability to effectively simulate diseased tissue. Studies have shown endocardial stimulation in closer proximity to the specialized conduction system is more effective when compared with epicardial stimulation. Several observational and acute haemodynamic studies have demonstrated improved electrical resynchronization and echocardiographic response with conduction system pacing (CSP). Our objective is to provide a systematic review of the evolution of CRT, and an introduction to CSP as an intriguing, though experimental physiologic alternative to conventional CRT.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: [email protected]

Europace: 27 Nov 2020; epub ahead of print
Herweg B, Welter-Frost A, Vijayaraman P
Europace: 27 Nov 2020; epub ahead of print | PMID: 33247913
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Abstract

Reconstruction of three-dimensional biventricular activation based on the 12-lead electrocardiogram via patient-specific modelling.

Pezzuto S, Prinzen FW, Potse M, Maffessanti F, ... Krause R, Auricchio A
Aims
Non-invasive imaging of electrical activation requires high-density body surface potential mapping. The nine electrodes of the 12-lead electrocardiogram (ECG) are insufficient for a reliable reconstruction with standard inverse methods. Patient-specific modelling may offer an alternative route to physiologically constraint the reconstruction. The aim of the study was to assess the feasibility of reconstructing the fully 3D electrical activation map of the ventricles from the 12-lead ECG and cardiovascular magnetic resonance (CMR).
Methods and results
Ventricular activation was estimated by iteratively optimizing the parameters (conduction velocity and sites of earliest activation) of a patient-specific model to fit the simulated to the recorded ECG. Chest and cardiac anatomy of 11 patients (QRS duration 126-180 ms, documented scar in two) were segmented from CMR images. Scar presence was assessed by magnetic resonance (MR) contrast enhancement. Activation sequences were modelled with a physiologically based propagation model and ECGs with lead field theory. Validation was performed by comparing reconstructed activation maps with those acquired by invasive electroanatomical mapping of coronary sinus/veins (CS) and right ventricular (RV) and left ventricular (LV) endocardium. The QRS complex was correctly reproduced by the model (Pearson\'s correlation r = 0.923). Reconstructions accurately located the earliest and latest activated LV regions (median barycentre distance 8.2 mm, IQR 8.8 mm). Correlation of simulated with recorded activation time was very good at LV endocardium (r = 0.83) and good at CS (r = 0.68) and RV endocardium (r = 0.58).
Conclusion
Non-invasive assessment of biventricular 3D activation using the 12-lead ECG and MR imaging is feasible. Potential applications include patient-specific modelling and pre-/per-procedural evaluation of ventricular activation.

© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.

Europace: 25 Nov 2020; epub ahead of print
Pezzuto S, Prinzen FW, Potse M, Maffessanti F, ... Krause R, Auricchio A
Europace: 25 Nov 2020; epub ahead of print | PMID: 33241411
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Abstract

Cryoablation vs. radiofrequency ablation of the atrioventricular node in patients with His-bundle pacing.

Zweerink A, Bakelants E, Stettler C, Burri H
Aims
Radiofrequency ablation (RFA) of the atrioventricular node (AVN) with His-bundle pacing (HBP) can cause rise in capture thresholds. Cryoablation (CRYO) may offer reversibility in case of threshold rise but has never been tested for AVN ablation in this setting. Our aim was to compare procedural characteristics and outcome of CRYO compared with RFA for AVN ablation in patients with HBP.
Methods and results
Forty-four patients with HBP underwent AVN ablation for an \'ablate and pace\' indication. Cryoablation was performed in the first 22 patients and RFA in the following 22 patients. Procedural characteristics, success rates, and change in His capture thresholds were compared between groups. Distance from the ablation site to the His lead was measured using biplane fluoroscopy. Acute success was 100% with both strategies. Median procedural duration was significantly longer for CRYO {50 [interquartile range (IQR) 38-63] min} compared with RFA [36 (IQR, 30-41) min; P = 0.027]. An acute threshold rise of ≥1 V was observed in four CRYO (one complete loss of capture) and three RFA patients (P = 0.38), with all of the applications being within 6 mm of the His lead tip. During follow-up, nine patients had AVN re-conduction (six CRYO vs. three RFA; P = 0.58), but only four patients required a redo procedure (all CRYO; P = 0.09).
Conclusion
Cryoablation does not offer any advantage over RFA for AVN ablation in patients with HBP and tended to require more redo procedures. If possible, a distance of ≥6 mm should be maintained from the His lead tip to avoid a rise in capture thresholds.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: [email protected]

Europace: 25 Nov 2020; epub ahead of print
Zweerink A, Bakelants E, Stettler C, Burri H
Europace: 25 Nov 2020; epub ahead of print | PMID: 33241283
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Abstract

Interpretation of clinical studies in electrophysiology: statistical considerations for the clinician.

Chieng D, Finch S, Sugumar H, Taylor AJ, ... Kalman JM, Kistler PM

Atrial fibrillation (AF) outcome studies play an essential role in the development of clinical evidence to improve the management of AF patients. Understanding the statistical considerations involved in study design and interpretation is crucial if electrophysiologists are to change practice. In this review, with the guidance of a medical statistician and a clinical trialist we provide an overview of important statistical issues for the clinician, with a focus on clinical studies in AF ablation. Various types of study designs including randomized controlled trials, superiority, and non-inferiority studies are described, along with their implications and limitations. Appropriate sample size calculation is fundamental to ensure statistical power and efficient resource use. Multiplicity in study endpoints is useful to encapsulate the varied effects of an intervention/treatment, although statistical adjustments are required to account for this. Finally, we discuss the limitations with the current primary endpoint used in AF ablation studies, namely, freedom from atrial tachyarrhythmia of >30 seconds, and propose AF burden as a more relevant primary endpoint, based on findings from recent clinical studies. However, technical challenges need to be overcome before AF burden can be routinely adopted, especially the need for non-invasive, long-term monitoring. The emergence of newer technologies, particularly wearable technology, offers significant promise in filling this gap.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: [email protected]

Europace: 24 Nov 2020; epub ahead of print
Chieng D, Finch S, Sugumar H, Taylor AJ, ... Kalman JM, Kistler PM
Europace: 24 Nov 2020; epub ahead of print | PMID: 33236092
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Abstract

His bundle pacing capture threshold stability during long-term follow-up and correlation with lead slack.

Beer D, Subzposh FA, Colburn S, Naperkowski A, Vijayaraman P
Aims
His bundle pacing (HBP) is the most physiologic form of pacing. Long-term HBP capture threshold stability and its relation to lead characteristics at the time of implantation have not been adequately described. The aim of this study was to characterize HB capture threshold in follow-up and to identify potential lead characteristics predictive of lead capture instability.
Methods and results
Consecutive patients with successful HBP for bradycardia indications were identified from the Geisinger HBP registry. His bundle capture thresholds, baseline comorbidities, and radiographic lead slack characteristics were analysed. An increase in HB capture threshold ≥1 V above implant values at any time during follow-up was tracked. Forty-four of the 294 studied (15%) experienced HB capture threshold increase by ≥ 1 V. Threshold increase was seen early (41% by 8 weeks, 66% by 1 year). Eighteen (6%) patients required lead revision in follow-up. Abnormal slack shape was associated with a trend toward capture threshold increase [hazard ratio (HR) 2.07; 95% confidence interval (CI) 0.9-4.6; P = 0.08]. Non-perpendicular angle of lead insertion on radiography was associated with the capture threshold increase (HR 2.81, 95% CI 1.4-5.8; P < 0.01).
Conclusion
His bundle capture threshold remains stable in the majority (85%) of patients. Implant characteristics may predict the threshold rise. Further evaluation of the aetiology of threshold increase and design changes in lead and delivery systems may lead to chronically stable capture thresholds.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: [email protected]

Europace: 24 Nov 2020; epub ahead of print
Beer D, Subzposh FA, Colburn S, Naperkowski A, Vijayaraman P
Europace: 24 Nov 2020; epub ahead of print | PMID: 33236070
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Abstract

Effect of alcohol consumption on the risk of adverse events in atrial fibrillation: from the COmparison study of Drugs for symptom control and complication prEvention of Atrial Fibrillation (CODE-AF) registry.

Lim C, Kim TH, Yu HT, Lee SR, ... Lee YS, Joung B
Aims
The aim of this study is to determine the relationship between alcohol consumption and atrial fibrillation (AF)-related adverse events in the AF population.
Methods and results
A total of 9411 patients with nonvalvular AF in a prospective observational registry were categorized into four groups according to the amount of alcohol consumption-abstainer-rare, light (<100 g/week), moderate (100-200 g/week), and heavy (≥200 g/week). Data on adverse events (ischaemic stroke, transient ischaemic attack, systemic embolic event, or AF hospitalization including for AF rate or rhythm control and heart failure management) were collected for 17.4 ± 7.3 months. A Cox proportional hazard models was performed to calculate hazard ratios (HRs), and propensity score matching was conducted to validate the results. The heavy alcohol consumption group showed an increased risk of composite adverse outcomes [adjusted hazard ratio (aHR) 1.32, 95% confidence interval (CI) 1.06-1.66] compared with the reference group (abstainer-rare group). However, no significant increased risk for adverse outcomes was observed in the light (aHR 0.88, 95% CI 0.68-1.13) and moderate (aHR 0.91, 95% CI 0.63-1.33) groups. In subgroup analyses, adverse effect of heavy alcohol consumption was significant, especially among patients with low CHA2DS2-VASc score, without hypertension, and in whom β-blocker were not prescribed.
Conclusion
Our findings suggest that heavy alcohol consumption increases the risk of adverse events in patients with AF, whereas light or moderate alcohol consumption does not.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: [email protected]

Europace: 22 Nov 2020; epub ahead of print
Lim C, Kim TH, Yu HT, Lee SR, ... Lee YS, Joung B
Europace: 22 Nov 2020; epub ahead of print | PMID: 33227134
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Abstract

Pediatric catheter ablation at the beginning of the 21st century: results from the European Multicenter Pediatric Catheter Ablation Registry \'EUROPA\'.

Krause U, Paul T, Bella PD, Gulletta S, ... Ferrari P, De Filippo P
Aims
Contemporary data from prospective multicentre registries on catheter ablation in pediatric patients are sparse. Aim of the European Pediatric Catheter Ablation Registry EUROPA was to contribute data to fill this gap of knowledge.
Methods and results
From July 2012 to June 2017, data on catheter ablation in pediatric patients (≤18 years of age) including a 1-year follow-up from five European pediatric EP centres were collected prospectively. A total of 683 patients (mean age 12.4 ± 3.9 years, mean body weight 50.2 ± 19 kg) were enrolled. Target tachycardia was WPW/atrioventricular-nodal re-entrant tachycardia (AVRT) in 380 (55.7%) patients, AVNRT in 230 (33.8%) patients, ventricular tachycardia (VT) in 24 (3.5) patients, focal atrial tachycardia (FAT) in 20 (2.9%) patients, IART in 14 (2%) patients, and junctional ectopic tachycardia in 3 (0.45) patients. Overall procedural success was 95.6%. Compared with all other substrates, success was significantly lower in FAT patients (80%, n = 16, P = 0.001). Mean procedure duration was 136 ± 67 min and mean fluoroscopy time was 4.9 ± 6.8 min. Major complications occurred in 0.7% of the patients. No persisting AV block requiring permanent pacing was reported. At 1-year follow-up (605/683 patients, 95%), tachycardia recurrence was reported in 7.8% of patients. Recurrence after VT ablation (33%) was significantly higher (P = 0.001) than after ablation of all other substrates.
Conclusion
The present study proves overall high efficacy and safety of catheter ablation of various tachycardia substrates in pediatric patients. Of note, complication rate was exceptionally low. Long-term success was high except for patients after VT ablation.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: [email protected]

Europace: 22 Nov 2020; epub ahead of print
Krause U, Paul T, Bella PD, Gulletta S, ... Ferrari P, De Filippo P
Europace: 22 Nov 2020; epub ahead of print | PMID: 33227133
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Abstract

Accuracy of left atrial fibrosis detection with cardiac magnetic resonance: correlation of late gadolinium enhancement with endocardial voltage and conduction velocity.

Caixal G, Alarcón F, Althoff TF, Nuñez-Garcia M, ... Guasch E, Mont L
Aims
Myocardial fibrosis is a hallmark of atrial fibrillation (AF) and its characterization could be used to guide ablation procedures. Late gadolinium enhanced-magnetic resonance imaging (LGE-MRI) detects areas of atrial fibrosis. However, its accuracy remains controversial. We aimed to analyse the accuracy of LGE-MRI to identify left atrial (LA) arrhythmogenic substrate by analysing voltage and conduction velocity at the areas of LGE.
Methods and results
Late gadolinium enhanced-magnetic resonance imaging was performed before ablation in 16 patients. Atrial wall intensity was normalized to blood pool and classified as healthy, interstitial fibrosis, and dense scar tissue depending of the resulting image intensity ratio. Bipolar voltage and local conduction velocity were measured in LA with high-density electroanatomic maps recorded in sinus rhythm and subsequently projected into the LGE-MRI. A semi-automatic, point-by-point correlation was made between LGE-MRI and electroanatomical mapping. Mean bipolar voltage and local velocity progressively decreased from healthy to interstitial fibrosis to scar. There was a significant negative correlation between LGE with voltage (r = -0.39, P < 0.001) and conduction velocity (r = -0.25, P < 0.001). In patients showing dilated atria (LA diameter ≥45 mm) the conduction velocity predictive capacity of LGE-MRI was weaker (r = -0.40 ± 0.09 vs. -0.20 ± 0.13, P = 0.02).
Conclusions
Areas with higher LGE show lower voltage and slower conduction in sinus rhythm. The enhancement intensity correlates with bipolar voltage and conduction velocity in a point-by-point analysis. The performance of LGE-MRI in assessing local velocity might be reduced in patients with dilated atria (LA diameter ≥45).

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Europace: 22 Nov 2020; epub ahead of print
Caixal G, Alarcón F, Althoff TF, Nuñez-Garcia M, ... Guasch E, Mont L
Europace: 22 Nov 2020; epub ahead of print | PMID: 33227129
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Impact:
Abstract

Changing paradigms: from prevention of thromboembolic events to improved survival in patients with atrial fibrillation.

Escobar C, Camm AJ

Atrial fibrillation is associated with a five-fold increase in the risk of stroke. Current guidelines recommend the use of the CHA2DS2-VASc score to stratify the risk of stroke. In addition, guidelines recommend the identification of the conditions that increase the risk of haemorrhage to be modified and thus decrease the risk of bleeding. Nevertheless, many patients with a high thromboembolic risk are prescribed antiplatelet treatment or do not receive any antithrombotic therapy. In addition, therapeutic inertia is common in anticoagulated patients taking vitamin K antagonists, and underdosing is an emerging problem with direct oral anticoagulants, probably because many physicians consider the risk of stroke and the risk of major bleeding to be equal. It is necessary to develop a new approach to risk stratification, an approach that moves from morbidity to mortality, i.e., from stratification of the risk of stroke and major bleeding to stratification of the risk of mortality associated with stroke and the risk of mortality associated with bleeding. In this article, we propose a novel risk stratification approach based on the mortality associated with stroke and bleeding, illustrated by data derived from the literature.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: [email protected]

Europace: 21 Nov 2020; epub ahead of print
Escobar C, Camm AJ
Europace: 21 Nov 2020; epub ahead of print | PMID: 33221894
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Impact:
Abstract

Clinical outcomes and programming strategies of implantable cardioverter-defibrillator devices in paediatric hypertrophic cardiomyopathy: a UK National Cohort Study.

Norrish G, Chubb H, Field E, McLeod K, ... Mangat J, Kaski JP
Aims
Sudden cardiac death (SCD) is the most common mode of death in paediatric hypertrophic cardiomyopathy (HCM). This study describes the implant and programming strategies with clinical outcomes following implantable cardioverter-defibrillator (ICD) insertion in a well-characterized national paediatric HCM cohort.
Methods and results
Data from 90 patients undergoing ICD insertion at a median age 13 (±3.5) for primary (n = 67, 74%) or secondary prevention (n = 23, 26%) were collected from a retrospective, longitudinal multi-centre cohort of children (<16 years) with HCM from the UK. Seventy-six (84%) had an endovascular system [14 (18%) dual coil], 3 (3%) epicardial, and 11 (12%) subcutaneous system. Defibrillation threshold (DFT) testing was performed at implant in 68 (76%). Inadequate DFT in four led to implant adjustment in three patients. Over a median follow-up of 54 months (interquartile range 28-111), 25 (28%) patients had 53 appropriate therapies [ICD shock n = 45, anti-tachycardia pacing (ATP) n = 8], incidence rate 4.7 per 100 patient years (95% CI 2.9-7.6). Eight inappropriate therapies occurred in 7 (8%) patients (ICD shock n = 4, ATP n = 4), incidence rate 1.1/100 patient years (95% CI 0.4-2.5). Three patients (3%) died following arrhythmic events, despite a functioning device. Other device complications were seen in 28 patients (31%), including lead-related complications (n = 15) and infection (n = 10). No clinical, device, or programming characteristics predicted time to inappropriate therapy or lead complication.
Conclusion
In a large national cohort of paediatric HCM patients with an ICD, device and programming strategies varied widely. No particular strategy was associated with inappropriate therapies, missed/delayed therapies, or lead complications.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: [email protected]

Europace: 21 Nov 2020; epub ahead of print
Norrish G, Chubb H, Field E, McLeod K, ... Mangat J, Kaski JP
Europace: 21 Nov 2020; epub ahead of print | PMID: 33221861
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Impact:
Abstract

Clinical characterization of the first Belgian SCN5A founder mutation cohort.

Sieliwonczyk E, Alaerts M, Robyns T, Schepers D, ... Saenen J, Loeys B
Aims
We identified the first Belgian SCN5A founder mutation, c.4813 + 3_4813 + 6dupGGGT. To describe the clinical spectrum and disease severity associated with this mutation, clinical data of 101 SCN5A founder mutation carriers and 46 non-mutation carrying family members from 25 Belgian families were collected.
Methods and results
The SCN5A founder mutation was confirmed by haplotype analysis. The clinical history and electrocardiographic parameters of the mutation carriers and their family members were gathered and compared. A cardiac electrical abnormality was observed in the majority (82%) of the mutation carriers. Cardiac conduction defects, defined as PR or QRS prolongation on electrocardiogram (ECG), were most frequent, occurring in 65% of the mutation carriers. Brugada syndrome (BrS) was the second most prevalent phenotype identified in 52%, followed by atrial dysrythmia in 11%. Overall, 33% of tested mutation carriers had a normal sodium channel blocker test. Negative tests were more common in family members distantly related to the proband. Overall, 23% of the mutation carriers were symptomatic, with 8% displaying major adverse events. As many as 13% of the patients tested with a sodium blocker developed ventricular arrhythmia. One family member who did not carry the founder mutation was diagnosed with BrS.
Conclusion
The high prevalence of symptoms and sensitivity to sodium channel blockers in our founder population highlights the adverse effect of the founder mutation on cardiac conduction. The large phenotypical heterogeneity, variable penetrance, and even non-segregation suggest that other genetic (and environmental) factors modify the disease expression, severity, and outcome in these families.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: [email protected]

Europace: 21 Nov 2020; epub ahead of print
Sieliwonczyk E, Alaerts M, Robyns T, Schepers D, ... Saenen J, Loeys B
Europace: 21 Nov 2020; epub ahead of print | PMID: 33221854
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Impact:
Abstract

Diagnostic yield and accuracy in a tertiary referral syncope unit validating the ESC guideline on syncope: a prospective cohort study.

de Jong JSY, Blok MRS, Thijs RD, Harms MPM, ... van Dijk N, de Lange FJ
Aims 
To assess in patients with transient loss of consciousness the diagnostic yield, accuracy, and safety of the structured approach as described in the ESC guidelines in a tertiary referral syncope unit.
Methods and results 
Prospective cohort study including 264 consecutive patients (≥18 years) referred with at least one self-reported episode of transient loss of consciousness and presenting to the syncope unit between October 2012 and February 2015. The study consisted of three phases: history taking (Phase 1), autonomic function tests (AFTs) (Phase 2), and after 1.5-year follow-up with assessment by a multidisciplinary committee (Phase 3). Diagnostic yield was assessed after Phases 1 and 2. Empirical diagnostic accuracy was measured for diagnoses according to the ESC guidelines after Phase 3. The diagnostic yield after Phase 1 (history taking) was 94.7% (95% CI: 91.1-97.0%, 250/264 patients) and increased to 97.0% (93.9-98.6%, 256/264 patients) after Phase 2. The overall diagnostic accuracy (as established in Phase 3) of the Phases 1 and 2 diagnoses was 90.6% (95% CI: 86.2-93.8%, 232/256 patients). No life-threatening conditions were missed. Three patients died, two unrelated to the cause of transient loss of consciousness, and one whom remained undiagnosed.
Conclusion 
A clinical work-up at a tertiary syncope unit using the ESC guidelines has a high diagnostic yield, accuracy, and safety. History taking (Phase 1) is the most important diagnostic tool. Autonomic function tests never changed the Phase 1 diagnosis but helped to increase the certainty of the Phase 1 diagnosis in many patients and yield additional diagnoses in patients who remained undiagnosed after Phase 1. Diagnoses were inaccurate in 9.4%, but no serious conditions were missed. This is adequate for clinical practice.

© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.

Europace: 20 Nov 2020; epub ahead of print
de Jong JSY, Blok MRS, Thijs RD, Harms MPM, ... van Dijk N, de Lange FJ
Europace: 20 Nov 2020; epub ahead of print | PMID: 33219671
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Impact:
Abstract

Incidence, epidemiology, diagnosis and prognosis of atrio-oesophageal fistula following percutaneous catheter ablation: a French nationwide survey.

Gandjbakhch E, Mandel F, Dagher Y, Hidden-Lucet F, Rollin A, Maury P
Aims
Rate, incidence, risk factors, and optimal management of atrio-oesophageal fistula (AOF) after catheter ablation for atrial fibrillation (AF) remain obscure.
Methods and results
All French centres performing AF ablation were identified and surveys were sent concerning the number of procedures, eventual cases of AOF, and characteristics of such cases. Eighty-two of the 103 centres (80%) performing AF ablation in France were included, with a total of 129 286 AF ablations since 2006 (93% of the whole procedures in France). Thirty-three AOF were reported (reported rate 0.026% per procedure) with a stable reported annual incidence despite the increasing number of procedures. Sensitivity of computed tomography (CT) scan for AOF was 81%. Mortality was 60%, significantly lower in case of surgical corrective therapy (31 vs. 93%, P = 0.001).
Conclusion
The reported rate of AOF after AF ablation in this nationwide survey was 0.026%, with a stable reported annual incidence over time. A normal CT scan does not rule out the diagnosis and should be repeated in case of suspicion. Prognosis remains poor with a mortality of 60% and crucially dependant of immediate surgical correction. No clear protective strategy has been proven effective.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: [email protected]

Europace: 20 Nov 2020; epub ahead of print
Gandjbakhch E, Mandel F, Dagher Y, Hidden-Lucet F, Rollin A, Maury P
Europace: 20 Nov 2020; epub ahead of print | PMID: 33221901
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Impact:
Abstract

Prognostic impact of multiple fragmented QRS on cardiac events in idiopathic dilated cardiomyopathy.

Marume K, Noguchi T, Kamakura T, Tateishi E, ... Ogawa H, Yasuda S
Aims 
To evaluate the prognostic impact of fragmented QRS (fQRS) on idiopathic dilated cardiomyopathy (DCM).
Methods and results 
We conducted a prospective observational study of 290 consecutive patients with DCM (left ventricular ejection fraction ≤ 40%) and narrow QRS who underwent cardiac magnetic resonance. We defined fQRS as the presence of various RSR\' patterns in ≥2 contiguous leads representing the anterior (V1-V5), inferior (II, III, and aVF), or lateral (I, aVL, and V6) myocardial segments. Multiple fQRS was defined as the presence of fQRS in ≥2 myocardial segments. Patients were divided into three groups: no fQRS, single fQRS, or multiple fQRS. The primary endpoint was a composite of hard cardiac events consisting of heart failure death, sudden cardiac death (SCD), or aborted SCD. The secondary endpoints were all-cause death and arrhythmic event. During a median follow-up of 3.8 years (interquartile range, 1.8-6.2), 31 (11%) patients experienced hard cardiac events. Kaplan-Meier analysis showed that the rates of hard cardiac events and all-cause death were similar in the single-fQRS and no-fQRS groups and higher in the multiple-fQRS group (P = 0.004 and P = 0.017, respectively). Multivariable Cox regression identified that multiple fQRS is a significant predictor of hard cardiac events (hazard ratio, 2.23; 95% confidence interval, 1.07-4.62; P = 0.032). The multiple-fQRS group had the highest prevalence of a diffuse late gadolinium enhancement pattern (no fQRS, 21%; single fQRS, 22%; multiple fQRS, 39%; P < 0.001).
Conclusion 
Multiple fQRS, but not single fQRS, is associated with future hard cardiac events in patients with DCM.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: [email protected]

Europace: 18 Nov 2020; epub ahead of print
Marume K, Noguchi T, Kamakura T, Tateishi E, ... Ogawa H, Yasuda S
Europace: 18 Nov 2020; epub ahead of print | PMID: 33212485
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Impact:
Abstract

Safety, efficacy, and reproducibility of cavotricuspid isthmus ablation guided by the ablation index: acute results of the FLAI study.

Viola G, Stabile G, Bandino S, Rossi L, ... Barra S, Casu G
Aims
Ablation index (AI) is a marker of lesion quality during catheter ablation that incorporates contact force, time, and power in a weighted formula. This index was originally developed for pulmonary vein isolation as well as other left atrial procedures. The aim of our study is to evaluate the feasibility and efficacy of the AI for the ablation of the cavotricuspid isthmus (CTI) in patients presenting with typical atrial flutter (AFL).
Methods and results
This prospective multicentre non-randomized study enrolled 412 consecutive patients with typical AFL undergoing AI-guided cavotricuspid isthmus ablation. The procedure was performed targeting an AI of 500 and an inter-lesion distance measurement of ≤6 mm. The primary endpoints were CTI \'first-pass\' block and persistent block after a 20-min waiting time. Secondary endpoints included procedural and radiofrequency duration and fluoroscopic time. A total of 412 consecutive patients were enrolled in 31 centres (mean age 64.9 ± 9.8; 72.1% males and 27.7% with structural heart disease). The CTI bidirectional \'first-pass\' block was reached in 355 patients (88.3%), whereas CTI block at the end of the waiting time was achieved in 405 patients (98.3%). Mean procedural, radiofrequency, and fluoroscopic time were 56.5 ± 28.1, 7.8 ± 4.8, and 1.9 ± 4.8 min, respectively. There were no major procedural complications. There was no significant inter-operator variability in the ability to achieve any of the primary endpoints.
Conclusion
AI-guided ablation with an inter-lesion distance ≤6 mm represents an effective, safe, and highly reproducible strategy to achieve bidirectional block in the treatment of typical AFL.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: [email protected]

Europace: 18 Nov 2020; epub ahead of print
Viola G, Stabile G, Bandino S, Rossi L, ... Barra S, Casu G
Europace: 18 Nov 2020; epub ahead of print | PMID: 33212484
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Impact:
Abstract

Impact of contact force sensing technology on outcome of catheter ablation of idiopathic pre-mature ventricular contractions originating from the outflow tracts.

Reichlin T, Baldinger SH, Pruvot E, Bisch L, ... Kühne M, Sticherling C
Aims
Catheter ablation of frequent idiopathic pre-mature ventricular contractions (PVC) is increasingly performed. While potential benefits of contact force (CF)-sensing technology for atrial fibrillation ablation have been assessed in several studies, the impact of CF-sensing on ventricular arrhythmia ablation remains unknown. This study aimed to compare outcomes of idiopathic outflow tract PVC ablation when using standard ablation catheters as opposed to CF-sensing catheters.
Methods and results
In a retrospective multi-centre study, unselected patients undergoing catheter ablation of idiopathic outflow tract PVCs between 2013 and 2016 were enrolled. All procedures were performed using irrigated-tip ablation catheters and a 3D electro-anatomical mapping system. Sustained ablation success was defined as a  ≥80% reduction of pre-procedural PVC burden determined by 24 h Holter ECG during follow-up. Overall, 218 patients were enrolled (median age 52 years, 51% males). Baseline and procedural data were similar in the standard ablation (24%) and the CF-sensing group (76%). Overall, the median PVC burden decreased from 21% (IQR 10-30%) before ablation to 0.2% (IQR 0-3.0%) after a median follow-up of 2.3 months (IQR 1.4-3.9 months). The rates of both acute (91% vs. 91%, P = 0.94) and sustained success (79% vs. 74%, P = 0.44) were similar in the standard ablation and the CF-sensing groups. No differences were observed in subgroups according to arrhythmia origin from the RVOT (65%) or LVOT (35%). Complications were rare (1.8%) and evenly distributed between the two groups.
Conclusion
The use of CF-sensing technology is not associated with increased success rate nor decreased complication rate in idiopathic outflow tract PVC ablation.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: [email protected]

Europace: 17 Nov 2020; epub ahead of print
Reichlin T, Baldinger SH, Pruvot E, Bisch L, ... Kühne M, Sticherling C
Europace: 17 Nov 2020; epub ahead of print | PMID: 33207371
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Impact:
Abstract

Pulmonary vein isolation alone vs. more extensive ablation with defragmentation and linear ablation of persistent atrial fibrillation: the EARNEST-PVI trial.

Inoue K, Hikoso S, Masuda M, Furukawa Y, ... Nakatani D, Sakata Y
Aims
Previous studies could not demonstrate any benefit of more intensive ablation in addition to pulmonary vein isolation (PVI) including complex fractionated atrial electrogram (CFAE) and linear ablation for recurrence in the initial catheter ablation of persistent atrial fibrillation (AF). This study aimed to establish the non-inferiority of PVI alone to PVI plus these additional ablation strategies.
Methods and results
Patients with persistent AF who underwent an initial catheter ablation (n = 512, long-standing persistent AF; 128 cases) were randomly assigned in a 1:1 ratio to either PVI alone (PVI-alone group) or PVI plus CFAE and/or linear ablation (PVI-plus group). After excluding 15 cases who did not receive procedures, we analysed 249 and 248 patients, respectively. The primary endpoint was recurrence of AF, atrial flutter, and/or atrial tachycardia, and the non-inferior margin was set at a hazard ratio of 1.43. In the PVI-plus group, 85.1% of patients had linear ablation and 15.3% CFAE ablation. After 12 months, freedom from the primary endpoint occurred in 71.3% of patients in the PVI-alone group and in 78.3% in the PVI-plus group [hazard ratio = 1.56 (95% confidence interval: 1.10-2.24), non-inferior P = 0.3062]. The procedure-related complication rates were 2.0% in the PVI-alone group and 3.6% in the PVI-plus group (P = 0.199).
Conclusion
This randomized trial did not establish the non-inferiority of PVI alone to PVI plus linear ablation or CFAE ablation in patients with persistent AF, but implied that the PVI plus strategy was promising to improve the clinical efficacy (NCT03514693).

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: [email protected]

Europace: 16 Nov 2020; epub ahead of print
Inoue K, Hikoso S, Masuda M, Furukawa Y, ... Nakatani D, Sakata Y
Europace: 16 Nov 2020; epub ahead of print | PMID: 33200213
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Impact:
Abstract

Efficacy of multi-electrode linear irreversible electroporation.

Buist TJ, Groen MHA, Wittkampf FHM, Loh P, ... van Es R, Elvan A
Aims
We investigated the efficacy of linear multi-electrode irreversible electroporation (IRE) ablation in a porcine model.
Methods and results
The study was performed in six pigs (weight 60-75 kg). After median sternotomy and opening of the pericardium, a pericardial cradle was formed and filled with blood. A linear seven polar 7-Fr electrode catheter with 2.5 mm electrodes and 2.5 mm inter-electrode spacing was placed in good contact with epicardial tissue. A single IRE application was delivered using 50 J at one site and 100 J at two other sites, in random sequence, using a standard monophasic defibrillator connected to all seven electrodes connected in parallel. The pericardium and thorax were closed and after 3 weeks survival animals were euthanized. A total of 82 histological sections from all 18 electroporation lesions were analysed. A total of seven 50 J and fourteen 100 J epicardial IRE applications were performed. Mean peak voltages at 50 and 100 J were 1079.2 V ± 81.1 and 1609.5 V ± 56.8, with a mean peak current of 15.4 A ± 2.3 and 20.2 A ± 1.7, respectively. Median depth of the 50 and 100 J lesions were 3.2 mm [interquartile range (IQR) 3.1-3.6] and 5.5 mm (IQR 4.6-6.6) (P < 0.001), respectively. Median lesion width of the 50 and 100 J lesions was 3.9 mm (IQR 3.7-4.8) and 5.4 mm (IQR 5.0-6.3), respectively (P < 0.001). Longitudinal sections showed continuous lesions for 100 J applications.
Conclusion
Epicardial multi-electrode linear application of IRE pulses is effective in creating continuous deep lesions.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: [email protected]

Europace: 16 Nov 2020; epub ahead of print
Buist TJ, Groen MHA, Wittkampf FHM, Loh P, ... van Es R, Elvan A
Europace: 16 Nov 2020; epub ahead of print | PMID: 33200191
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Impact:
Abstract

Brugada syndrome and arrhythmogenic cardiomyopathy: overlapping disorders of the connexome?

Ben-Haim Y, Asimaki A, Behr ER

Arrhythmogenic cardiomyopathy (ACM) and Brugada syndrome (BrS) are inherited diseases characterized by an increased risk for arrhythmias and sudden cardiac death. Possible overlap between the two was suggested soon after the description of BrS. Since then, various studies focusing on different aspects have been published pointing to similar findings in the two diseases. More recent findings on the structure of the cardiac cell-cell junctions may unite the pathophysiology of both diseases and give further evidence to the theory that they may in part be variants of the same disease spectrum. In this review, we aim to summarize the studies indicating the pathophysiological, genetic, structural, and electrophysiological overlap between ACM and BrS.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: [email protected]

Europace: 16 Nov 2020; epub ahead of print
Ben-Haim Y, Asimaki A, Behr ER
Europace: 16 Nov 2020; epub ahead of print | PMID: 33200179
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Impact:
Abstract

Infanticide vs. inherited cardiac arrhythmias.

Brohus M, Arsov T, Wallace DA, Jensen HH, ... Overgaard MT, Schwartz PJ
Aims
In 2003, an Australian woman was convicted by a jury of smothering and killing her four children over a 10-year period. Each child died suddenly and unexpectedly during a sleep period, at ages ranging from 19 days to 18 months. In 2019 we were asked to investigate if a genetic cause could explain the deaths, as part of an inquiry into the mother\'s convictions.
Methods and results
Whole genomes or exomes of the mother and her four children were sequenced. Functional analysis of a novel CALM2 variant was performed by measuring Ca2+-binding affinity, interaction with calcium channels and channel function. We found two children had a novel calmodulin variant (CALM2 G114R) that was inherited maternally. Three genes (CALM1-3) encode identical calmodulin proteins. A variant in the corresponding residue of CALM3 (G114W) was recently reported in a child who died suddenly at age 4 and a sibling who suffered a cardiac arrest at age 5. We show that CALM2 G114R impairs calmodulin\'s ability to bind calcium and regulate two pivotal calcium channels (CaV1.2 and RyR2) involved in cardiac excitation contraction coupling. The deleterious effects of G114R are similar to those produced by G114W and N98S, which are considered arrhythmogenic and cause sudden cardiac death in children.
Conclusion
A novel functional calmodulin variant (G114R) predicted to cause idiopathic ventricular fibrillation, catecholaminergic polymorphic ventricular tachycardia, or mild long QT syndrome was present in two children. A fatal arrhythmic event may have been triggered by their intercurrent infections. Thus, calmodulinopathy emerges as a reasonable explanation for a natural cause of their deaths.

© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.

Europace: 16 Nov 2020; epub ahead of print
Brohus M, Arsov T, Wallace DA, Jensen HH, ... Overgaard MT, Schwartz PJ
Europace: 16 Nov 2020; epub ahead of print | PMID: 33200177
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Impact:
Abstract

Risk of arrhythmias after myocardial infarction in patients with left ventricular systolic dysfunction according to mode of revascularization: a Cardiac Arrhythmias and RIsk Stratification after Myocardial infArction (CARISMA) substudy.

Thomsen AF, Jacobsen PK, Køber L, Joergensen RM, ... Jacobsen UG, Jøns C
Aims
The Cardiac Arrhythmias and RIsk Stratification after Myocardial infArction (CARISMA) study was an observational trial including 312 patients with acute myocardial infarction (MI) and left ventricular ejection fraction (LVEF) <40%. Primary percutaneous intervention (pPCI) was introduced 2 years after start of the enrolment, dividing the population into two groups: pre- and post-pPCI. This substudy sought to describe the influence of the mode of revascularization on long-term risk of new-onset atrial fibrillation (AF), bradyarrhythmia, and ventricular tachycardia and the subsequent risk of relevant major cardiovascular events (MACE).
Methods and results
The study included the 268 patients without a history of AF. All patients received an implantable cardiac monitor (ICM) and were followed for 2 years. The choice of revascularization was made by the treating team independently of the trial and retrospectively divided into pPCI, subacute PCI, primary thrombolysis, or no revascularization. Endpoints were new-onset arrhythmia and MACE.A total of 77 patients received no revascularization, whereas 49 received thrombolysis only and 142 received any PCI. The adjusted hazard ratio (HR) for developing any arrhythmia and the subsequently risk of MACE were increased in non-revascularized or thrombolysed patients compared with PCI-patients (any arrhythmia, non-revascularization: HR = 1.7, P = 0.01 and thrombolysis: HR = 1.6, P = 0.05; MACE, non-revascularization: HR = 3.1, P = 0.05 and thrombolysis: HR = 3.1, P = 0.08). All HRs were adjusted for significant baseline and clinically considered covariates and stratified for calendar year.
Conclusion
This study is the first to demonstrate that the long-term risk of arrhythmia documented by an ICM and the subsequent risk of MACE were increased in non-revascularized or thrombolysed patients compared with PCI-patients in a post-MI population with LVEF <40%.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: [email protected]

Europace: 16 Nov 2020; epub ahead of print
Thomsen AF, Jacobsen PK, Køber L, Joergensen RM, ... Jacobsen UG, Jøns C
Europace: 16 Nov 2020; epub ahead of print | PMID: 33200171
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Impact:
Abstract

Role of the rabbit whole-heart model for electrophysiologic safety pharmacology of non-cardiovascular drugs.

Ellermann C, Wolfes J, Eckardt L, Frommeyer G

Plenty of non-cardiovascular drugs alter cardiac electrophysiology and may ultimately lead to life-threatening arrhythmias. In clinical practice, measuring the QT interval as a marker for the repolarization period is the most common tool to assess the electrophysiologic safety of drugs. However, the sole measurement of the QT interval may be insufficient to determine the proarrhythmic risk of non-cardiovascular agents. Several other markers are considered in pre-clinical safety testing to determine potential harm on cardiac electrophysiology. Besides measuring typical electrophysiologic parameters such as repolarization duration, whole-heart models allow the determination of potential predictors for proarrhythmia. Spatial and temporal heterogeneity as well as changes of shape of the action potential can be easily assessed. In addition, provocation manoeuvers (either by electrolyte imbalances or programmed pacing protocols) may induce sustained arrhythmias and thereby determine ventricular vulnerability to arrhythmias. Compared with the human heart, the rabbit heart possesses a similar distribution of ion currents that govern cardiac repolarization, resulting in a rectangular action potential configuration in both species. In addition, similar biophysical properties of rabbit and human cardiac ion channels lead to a comparable pharmacologic response in human and rabbit hearts. Of note, arrhythmia patterns resemble in both species due to the similar effective size of human and rabbit hearts. Thus, the rabbit heart is particularly suitable for testing the electrophysiologic safety of drugs. Several experimental setups have been developed for studying cardiac electrophysiology in rabbits, ranging from single cell to tissue preparations, whole-heart setups, and in vivo models.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: [email protected]

Europace: 16 Nov 2020; epub ahead of print
Ellermann C, Wolfes J, Eckardt L, Frommeyer G
Europace: 16 Nov 2020; epub ahead of print | PMID: 33200170
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Impact:
Abstract

Randomized comparison of oesophageal protection with a temperature control device: results of the IMPACT study.

Leung LWM, Bajpai A, Zuberi Z, Li A, ... Hayat J, Gallagher MM
Aims 
Thermal injury to the oesophagus is an important cause of life-threatening complication after ablation for atrial fibrillation (AF). Thermal protection of the oesophageal lumen by infusing cold liquid reduces thermal injury to a limited extent. We tested the ability of a more powerful method of oesophageal temperature control to reduce the incidence of thermal injury.
Methods and results 
A single-centre, prospective, double-blinded randomized trial was used to investigate the ability of the ensoETM device to protect the oesophagus from thermal injury. This device was compared in a 1:1 randomization with a control group of standard practice utilizing a single-point temperature probe. In the protected group, the device maintained the luminal temperature at 4°C during radiofrequency (RF) ablation for AF under general anaesthesia. Endoscopic examination was performed at 7 days post-ablation and oesophageal injury was scored. The patient and the endoscopist were blinded to the randomization. We recruited 188 patients, of whom 120 underwent endoscopy. Thermal injury to the mucosa was significantly more common in the control group than in those receiving oesophageal protection (12/60 vs. 2/60; P = 0.008), with a trend toward reduction in gastroparesis (6/60 vs. 2/60, P = 0.27). There was no difference between groups in the duration of RF or in the force applied (P value range= 0.2-0.9). Procedure duration and fluoroscopy duration were similar (P = 0.97, P = 0.91, respectively).
Conclusion 
Thermal protection of the oesophagus significantly reduces ablation-related thermal injury compared with standard care. This method of oesophageal protection is safe and does not compromise the efficacy or efficiency of the ablation procedure.

© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.

Europace: 16 Nov 2020; epub ahead of print
Leung LWM, Bajpai A, Zuberi Z, Li A, ... Hayat J, Gallagher MM
Europace: 16 Nov 2020; epub ahead of print | PMID: 33205201
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Impact:
Abstract

Complications related to elective generator replacement of the subcutaneous implantable defibrillator.

van der Stuijt W, Quast ABE, Baalman SWE, de Wilde KC, ... Wilde AAM, Knops RE
Aims
To guarantee uninterrupted function of the subcutaneous implantable cardioverter-defibrillator (S-ICD), the pulse generator needs to be surgically replaced before the battery is depleted. The risks related to this replacement substantially impact long-term outcome for S-ICD recipients, as the majority will undergo one or several of these procedures in their lifetime. We aim to describe the procedural characteristics of the replacement procedure and to provide an insight in the complications associated with these replacements.
Methods and results
In this retrospective analysis, data from replacement procedures and follow-up visits were collected from all patients who underwent elective S-ICD generator replacement in our tertiary centre from June 2014 until November 2019. Original device position was assessed using the PRAETORIAN score. Complications were defined as those requiring surgical intervention, systemic antibiotic treatment, or device extraction. Seventy-two patients were included, with a median follow-up of 1.9 years (IQR 0.6-3.3 years) after replacement. Battery depletion occurred after 5.9 ± 0.7 years. The pulse generator was repositioned in patients with a PRAETORIAN score ≥90 to minimize the defibrillation threshold. Although there was an increase in impedance compared to the implant procedure, first shock conversion rate during defibrillation testing was 91.4% with a success rate of 100% after multiple attempts. Two patients developed a complication after, respectively, 9 and 21 months, resulting in a complication rate of 1.4% per year.
Conclusion
With a median follow-up of 1.9 years, this study shows a low complication rate after S-ICD replacement, with a first shock conversion rate of 91.4%.

© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.

Europace: 15 Nov 2020; epub ahead of print
van der Stuijt W, Quast ABE, Baalman SWE, de Wilde KC, ... Wilde AAM, Knops RE
Europace: 15 Nov 2020; epub ahead of print | PMID: 33197266
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Abstract

Significance of post-pacing intervals shorter than tachycardia cycle length for successful catheter ablation of atypical flutter.

Dall\'Aglio PB, Johner N, Namdar M, Shah DC
Aims
During entrainment mapping of macro-reentrant tachycardias, the time difference (dPPI) between post-pacing interval (PPI) and tachycardia cycle length (TCL) is thought to be a function of the distance of the pacing site to the re-entry circuit and dPPI < 30 ms is considered within the re-entry circuit. This study assessed the importance of PPI < TCL as a successful target for atypical flutter ablation.
Methods and results
A total of 177 ablation procedures were investigated. Surface electrocardiograms (ECGs) were evaluated and combined activation and entrainment mapping were performed to choose ablation sites. Each entrainment sequence immediately preceding static radiofrequency delivery at the same site was analysed. A total of 545 entrainment sequences were analysed. dPPI < 0 ms was observed in 45.3% (247/545) sequences. Ablation resulted in tachycardia termination more often at sites with dPPI < 0 (27.8% vs. 14.5%, P < 0.001) and with a progressively increasingly inverse correlation between dPPI duration and ablation success [odds ratio (OR): 0.974; 95% confidence interval (CI) 0.960-0.988; P < 0.001]. Tachycardia termination or cycle length prolongation also occurred more often at sites with dPPI < 0 (50.6% vs. 33.2%, P < 0.001) and with a similar inverse correlation with dPPI duration (OR: 0.972; 95% CI 0.960-0.984; P < 0.001). Twelve-lead synchronous isoelectric intervals were observed in 64.4% (163/253) flutter ECGs and were associated with a dPPI < 0 (75.3% vs. 55.8%, P < 0.001).
Conclusion
When combined with activation mapping, a negative dPPI is a more effective parameter for identifying a target for successful ablation compared to a dPPI = 0-30 ms. Its occurrence is associated with a critical small narrow slow-conducting isthmus at the target site.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: [email protected]

Europace: 15 Nov 2020; epub ahead of print
Dall'Aglio PB, Johner N, Namdar M, Shah DC
Europace: 15 Nov 2020; epub ahead of print | PMID: 33197256
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Abstract

Anatomical-based percutaneous left stellate ganglion block in patients with drug-refractory electrical storm and structural heart disease: a single-centre case series.

Savastano S, Dusi V, Baldi E, Rordorf R, ... Oltrona Visconti L, De Ferrari GM
Aims
The adoption of percutaneous stellate ganglion blockade for the treatment of drug-refractory electrical storm (ES) has been increasingly reported; however, the time of onset of the anti-arrhythmic effects, the safety of a purely anatomical approach in conscious patients and the additional benefit of repeated procedures remain unclear.
Methods and results
This study included consecutive patients undergoing percutaneous left stellate ganglion blockade (PLSGB) in our centre for drug-refractory ES. Lidocaine, bupivacaine, or a combination of both were injected in the vicinity of the left stellate ganglion. Overall, 18 PLSGBs were performed in 11 patients (age 69 ± 13 years; 63.6% men, left ventricular ejection fraction 31.6 ± 16%). Seven patients received only one PLSGB; three underwent two procedures and one required three PLSGB and two continuous infusions to control ventricular arrhythmias (VAs). All PLSGBs were performed with an anatomical approach; lidocaine, alone, or in combination was used in 77.7% of the procedures. The median burden of VAs 1 h after each block was zero compared with five in the hour before (P < 0.001); 83% of the patients were free from VAs; the efficacy at 24 h increased with repeated blocks. The anti-arrhythmic efficacy of PLSGB was not related to anisocoria. No procedure-related complications were reported.
Conclusion
Anatomical-based PLSGB is a safe and rapidly effective treatment for refractory ES; repeated blocks provide additional benefits. Percutaneous left stellate ganglion blockade should be considered for stabilizing patients to allow further ES management.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: [email protected]

Europace: 14 Nov 2020; epub ahead of print
Savastano S, Dusi V, Baldi E, Rordorf R, ... Oltrona Visconti L, De Ferrari GM
Europace: 14 Nov 2020; epub ahead of print | PMID: 33190159
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