Journal: Europace

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Abstract

Efficacy and safety of the GOLD FORCE multicentre randomized clinical trial: multielectrode phased radiofrequency vs. irrigated radiofrequency single-tip catheter with contact force ablation for treatment of symptomatic paroxysmal atrial fibrillation.

Wintgens LIS, Klaver MN, Maarse M, Spitzer SG, ... Elvan A, Boersma LVA
Aims
Pulmonary vein isolation (PVI) for atrial fibrillation (AF) has become increasingly safe and effective with the evolution of single-tip ablation catheters aided by contact force sensing (ST-CF) and single-shot devices such as the second-generation pulmonary vein ablation catheter (PVAC) Gold multi-electrode array. The multicentre randomized GOLD FORCE trial was conducted to evaluate non-inferiority of safety and efficacy of PVAC Gold PVI compared to ST-CF ablation for paroxysmal AF.
Methods and results
The primary efficacy endpoint documented AF recurrence ≥30 s was assessed by time-to-first-event analysis after a 90-day blanking period using repeated 7-day Holters. Secondary endpoints include acute success and procedural characteristics. Safety endpoints included procedural complications, stroke/transient ischaemic attack (TIA), tamponade, bleeding, and access site complications. Two hundred and eight patients underwent randomization and PVI (103 assigned to PVAC Gold, 105 to ST-CF). Acute success rates were 95% and 97% for PVAC Gold and ST-CF, respectively. At 12 months, AF recurrence was observed in 46.6% of the PVAC Gold group and in 26.2% of the ST-CF group [absolute efficacy difference 20.4% (95% confidence interval, CI 7.5-33.2%), hazard ratio 2.05 (95% CI 1.28-3.29), P = 0.003]. PVAC Gold had significantly shorter procedure and ablation times. Complication rates were 5.7% and 4.9% for PVAC Gold and ST-CF, respectively (P = 0.782).
Conclusion
In this multicentre randomized clinical trial, ablation with ST-CF and PVAC Gold ablation catheters non-inferiority for efficacy was not met. AF recurrence was significantly more frequent in the PVAC Gold group compared to single-tip contact force group. Both groups had similarly low rates of adverse events. PVAC Gold ablation had significantly shorter procedure and ablation times.

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

Europace: 18 Jul 2021; epub ahead of print
Wintgens LIS, Klaver MN, Maarse M, Spitzer SG, ... Elvan A, Boersma LVA
Europace: 18 Jul 2021; epub ahead of print | PMID: 34279627
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Abstract

Atrial fibrillation and risk of venous thromboembolism: a Swedish Nationwide Registry Study.

Hornestam B, Adiels M, Wai Giang K, Hansson PO, Björck L, Rosengren A
Aims
Atrial fibrillation (AF) is associated with arterial thromboembolism, mainly ischaemic stroke, while venous thromboembolism (VTE) in AF is less well studied. The aim of this study, therefore, was to examine the relationship between AF and VTE, including pulmonary embolism (PE) and deep venous thrombosis (DVT).
Methods and results
AF cases without previous VTE, ischaemic stroke or pulmonary arterial hypertension were identified from the Swedish Inpatient Registry between 1987 and 2013 and compared to two population controls per case without AF matched for age, sex, and county with respect to the incidence of VTE, PE, and DVT. In total, 463 244 AF cases were compared to 887 336 population controls. In both men and women, VTE rates were higher among AF patients the first 30 days after an AF diagnosis [40.2 vs. 5.7 in men and 55.7 vs. 6.6 in women per 1000 person-years at risk, respectively; hazard ratios 6.64 (95% confidence interval, 5.74-7.69) and 7.56 (6.47-8.83)]; and then decreasing, simultaneously with an increasing number of AF patients being treated with oral anticoagulation. VTE risk was similar to controls after 9 months in men but remained slightly elevated in women.
Conclusion
AF is strongly associated with an increased risk of VTE during the first months after diagnosis.
Introduction:
of anticoagulant therapy soon after AF diagnosis might reduce the risk of VTE as well as of ischaemic stroke.

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

Europace: 18 Jul 2021; epub ahead of print
Hornestam B, Adiels M, Wai Giang K, Hansson PO, Björck L, Rosengren A
Europace: 18 Jul 2021; epub ahead of print | PMID: 34279622
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Abstract

Cardiovascular magnetic resonance-based predictors of complete left ventricular systolic functional recovery after rhythm restoration in patients with atrial tachyarrhythmia.

Stegmann C, Jahnke C, Lindemann F, Oebel S, ... Hindricks G, Paetsch I
Aims
To establish a cardiovascular magnetic resonance (CMR)-based prediction model for complete systolic left ventricular ejection fraction (LVEF) recovery for the distinction of \'arrhythmia-induced\' from \'arrhythmia-mediated\' cardiomyopathy in patients with atrial tachyarrhythmias.
Methods and results
Two hundred and fifty-three tachyarrhythmia patients referred for catheter ablation were enrolled and underwent CMR baseline imaging; patients with a reduced LVEF <50% at baseline and CMR imaging at 3-month follow-up after successful rhythm restoration constituted the final study population (n = 134). CMR at baseline consisted of standard functional cine imaging, determination of extracellular volume, and late gadolinium enhancement (LGE) imaging; follow-up CMR comprised standard functional cine imaging. Left ventricular end-diastolic volume index (LVEDVI) measurements were categorized in \'opposite\', \'normal\', and \'enlarged\'. At follow-up, 80% (107/134) presented with complete LVEF recovery, while in 20% (27/134) persistent LVEF impairment was observed. LVEDVI and LGE were independent predictors of complete LVEF recovery with LGE adding significant incremental value on logistic regression modelling. Model-derived probabilities for complete LVEF recovery in LVEDVI categories of opposite, normal, and enlarged for LGE negativity and positivity were 94%, 85%, and 29% and 77%, 55%, and 8%, respectively.
Conclusion
CMR-derived assessment of LVEDVI category and LGE allowed for identification of arrhythmia-induced cardiomyopathy with acceptable discriminative performance. Probabilities for complete LVEF recovery for the combination of opposite LVEDVI/LGE negativity and enlarged LVEDVI/LGE positivity were 94% and 8%, respectively. The CMR-based prediction model of complete LVEF recovery can be used to perform upfront stratification in atrial tachyarrhythmia-related LVEF impairment.

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

Europace: 18 Jul 2021; epub ahead of print
Stegmann C, Jahnke C, Lindemann F, Oebel S, ... Hindricks G, Paetsch I
Europace: 18 Jul 2021; epub ahead of print | PMID: 34279613
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Abstract

A meta-analysis of clinical risk factors for stroke in anticoagulant-naïve patients with atrial fibrillation.

Noubiap JJ, Feteh VF, Middeldorp ME, Fitzgerald JL, ... Lau DH, Sanders P
Aims
The aim of this study is to summarize data from prospective cohort studies on clinical predictors of stroke and systemic embolism in anticoagulant-naïve atrial fibrillation (AF) patients.
Methods and results
EMBASE, MEDLINE, Global Index Medicus, and Web of Science were searched to identify all studies published by 28 November 2019. Forty-seven studies reporting data from 1 756 984 participants in 15 countries were included. The pooled incidence of stroke in anticoagulant-naïve AF patients was 23.8 per 1000 person-years (95% CI 19.7-28.2). Older age was associated with incident stroke or systemic embolism, with a pooled hazard ratio (HR) of 2.14 (95% CI 1.85-2.47), 2.83 (95% CI 2.27-3.51), and 6.87 (95% CI 6.33-7.44) for age 65-75, ≥75, and ≥85 years, respectively. Other predictors of stroke or systemic embolism included history of stroke or TIA (HR 2.84, 95% CI 2.19-3.67), hypertension (HR 1.60, 95% CI 1.37-1.86), diabetes (HR 1.28, 95% CI 1.20-1.37), heart failure (HR 1.25, 95% CI 1.11-1.40), peripheral artery disease (pooled HR 1.35, 95% CI 1.04-1.75), vascular disease (pooled HR 1.21, 95% CI 1.06-1.39), and prior myocardial infarction (pooled HR 1.08, 95% CI 1.03-1.14). Female sex was a predictor of thromboembolism in studies outside Asia (HR 1.33, 95% CI 1.15-1.55), but not in those done in Asia (HR 0.95, 95% CI 0.81-1.10).
Conclusion
This study confirms age and prior stroke as the strongest predictors of stroke or systemic embolism in anticoagulant-naive AF patients. Other predictors include hypertension, diabetes, heart failure, and vascular disease. Female sex seems not to be universally associated with stroke or systemic embolism.

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

Europace: 18 Jul 2021; epub ahead of print
Noubiap JJ, Feteh VF, Middeldorp ME, Fitzgerald JL, ... Lau DH, Sanders P
Europace: 18 Jul 2021; epub ahead of print | PMID: 34279604
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Abstract

Complications of implantable cardioverter-defibrillator treatment in arrhythmogenic right ventricular cardiomyopathy.

Christensen AH, Platonov PG, Svensson A, Jensen HK, ... Bundgaard H, Svendsen JH
Aims
Treatment with implantable cardioverter-defibrillators (ICD) is a cornerstone for prevention of sudden cardiac death in arrhythmogenic right ventricular cardiomyopathy (ARVC). We aimed at describing the complications associated with ICD treatment in a multinational cohort with long-term follow-up.
Methods and results
The Nordic ARVC registry was established in 2010 and encompasses a large multinational cohort of ARVC patients, including their clinical characteristics, treatment, and events during follow-up. We included 299 patients (66% males, median age 41 years). During a median follow-up of 10.6 years, 124 (41%) patients experienced appropriate ICD shock therapy, 28 (9%) experienced inappropriate shocks, 82 (27%) had a complication requiring surgery (mainly lead-related, n = 75), and 99 (33%) patients experienced the combined endpoint of either an inappropriate shock or a surgical complication. The crude rate of first inappropriate shock was 3.4% during the first year after implantation but decreased after the first year and plateaued over time. Contrary, the risk of a complication requiring surgery was 5.5% the first year and remained high throughout the study period. The combined risk of any complication was 7.9% the first year. In multivariate cox regression, presence of atrial fibrillation/flutter was a risk factor for inappropriate shock (P < 0.05), whereas sex, age at implant, and device type were not (all P > 0.05).
Conclusion
Forty-one percent of ARVC patients treated with ICD experienced potentially life-saving ICD therapy during long-term follow-up. A third of the patients experienced a complication during follow-up with lead-related complications constituting the vast majority.

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

Europace: 18 Jul 2021; epub ahead of print
Christensen AH, Platonov PG, Svensson A, Jensen HK, ... Bundgaard H, Svendsen JH
Europace: 18 Jul 2021; epub ahead of print | PMID: 34279601
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Abstract

Worldwide sedation strategies for atrial fibrillation ablation: current status and evolution over the last decade.

Garcia R, Waldmann V, Vanduynhoven P, Nesti M, ... Boveda S, Duncker D
Catheter ablation for atrial fibrillation (AF) has become one of the most common procedures in the electrophysiology lab with rapidly increasing volumes. Peri-procedural anaesthesia for AF ablation varies between centres, from general anaesthesia to deep or conscious sedation. The aim of this survey was to assess current sedation practices for AF ablation worldwide and its evolution over the last decade. Centres regularly performing AF ablation responded to an online survey. A total of 297 centres participated in the survey. Overall, the median (interquartile range) number of AF ablation procedures increased from 91 (43-200) to 200 (74-350) per year (P < 0.001) between 2010 and 2019. The proportion of cryoablation also increased from 17.0% to 33.2% (P < 0.001). In 2019, the most used sedation technique was general anaesthesia (40.5%), followed by conscious sedation (32.0%) and deep sedation (27.5%). Between 2010 and 2019, the proportion of procedures performed under general anaesthesia (+4.4%; P = 0.02) and deep sedation (+4.8%; P < 0.01) increased, whereas the use of conscious sedation decreased (-9.2%; P < 0.001). The most commonly used hypnotic drugs were propofol and midazolam, whereas the most commonly used opioid drugs were remifentanyl and fentanyl. This worldwide survey shows that the number of AF ablation procedures has more than doubled over the last decade and general anaesthesia remains most commonly used. Studies comparing outcomes between different sedation strategies are needed to guide optimal decision-making.

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

Europace: 18 Jul 2021; epub ahead of print
Garcia R, Waldmann V, Vanduynhoven P, Nesti M, ... Boveda S, Duncker D
Europace: 18 Jul 2021; epub ahead of print | PMID: 34308973
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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: journals.permis[email protected]

Europace: 17 Jul 2021; 23:996-1002
Mascia G, Bona RD, Ameri P, Canepa M, ... Crotti L, Brignole M
Europace: 17 Jul 2021; 23:996-1002 | PMID: 33367713
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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.

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Europace: 17 Jul 2021; 23:985-995
Finocchiaro G, Sheikh N, Leone O, Westaby J, ... Sheppard MN, Olivotto I
Europace: 17 Jul 2021; 23:985-995 | PMID: 33447843
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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: 17 Jul 2021; 23:1063-1071
Donnellan E, Wazni OM, Chung MK, Elshazly MB, ... Saliba W, Jaber W
Europace: 17 Jul 2021; 23:1063-1071 | PMID: 33463688
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Abstract

Alpha 1-adrenoceptor signalling contributes to toxic effects of catecholamine on electrical properties in cardiomyocytes.

Huang M, Fan X, Yang Z, Cyganek L, ... Akin I, Borggrefe M
Aims
This study aimed to investigate possible roles and underlying mechanisms of alpha-adrenoceptor coupled signalling for the pathogenesis of Takotsubo syndrome (TTS).
Methods and results
Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) were treated with a toxic concentration of epinephrine (Epi, 0.5 mM for 1 h) to mimic the setting of TTS. Patch-clamp technique, polymerase chain reaction (PCR) and Fluorescence-activated cell sorting (FACS) were employed for the study. High concentration Epi suppressed the depolarization velocity, prolonged duration of action potentials and induced arrhythmic events in hiPSC-CMs. The Epi effects were attenuated by an alpha-adrenoceptor blocker (phentolamine), suggesting involvement of alpha-adrenoceptor signalling in arrhythmogenesis related to QT interval prolongation in the setting of TTS. An alpha 1-adrenoceptor agonist (phenylephrine) but not an alpha 2-adrenoceptor agonist (clonidine) mimicked Epi effects. Epi enhanced ROS production, which could be attenuated by the alpha- adrenoceptor blocker. Treatment of cells with H2O2 (100 µM) mimicked the effects of Epi on action potentials and a reactive oxygen species (ROS)-blocker (N-acetyl-I-cysteine, 1 mM) prevented the Epi effects, indicating that the ROS signalling is involved in the alpha-adrenoceptor actions. Nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) oxidases were involved in alpha 1-adrenoceptor signalling. A protein kinase C (PKC) blocker suppressed the effects of Epi, phenylephrine and ROS as well, implying that PKC participated in alpha 1-adrenoceptor signalling and acted as a downstream factor of ROS. The abnormal action potentials resulted from alpha 1-adrenoceptor activation-induced dysfunctions of ion channels including the voltage-dependent Na+ and L-type Ca2+ channels.
Conclusions
Alpha 1-adrenoceptor signalling plays important roles for arrhythmogenesis of TTS. Alpha-adrenoceptor blockers might be clinically helpful for treating arrhythmias in patients with TTS.

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

Europace: 17 Jul 2021; 23:1137-1148
Huang M, Fan X, Yang Z, Cyganek L, ... Akin I, Borggrefe M
Europace: 17 Jul 2021; 23:1137-1148 | PMID: 33604602
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Abstract

Local catheter impedance drop during pulmonary vein isolation predicts acute conduction block in patients with paroxysmal atrial fibrillation: initial results of the LOCALIZE clinical trial.

Das M, Luik A, Shepherd E, Sulkin M, ... Ramos P, García-Bolao I
Aims
Radiofrequency ablation creates irreversible cardiac damage through resistive heating and this temperature change results in a generator impedance drop. Evaluation of a novel local impedance (LI) technology measured exclusively at the tip of the ablation catheter found that larger LI drops were indicative of more effective lesion formation. We aimed to evaluate whether LI drop is associated with conduction block in patients with paroxysmal atrial fibrillation (AF) undergoing pulmonary vein isolation (PVI).
Methods and results
Sixty patients underwent LI-blinded de novo PVI using a point-by-point ablation workflow. Pulmonary vein rings were divided into 16 anatomical segments. After a 20-min waiting period, gaps were identified on electroanatomic maps. Median LI drop within segments with inter-lesion distance ≤6 mm was calculated offline. The diagnostic accuracy of LI drop for predicting segment block was assessed using receiver operating characteristic analysis. For segments with inter-lesion distance ≤6 mm, acutely blocked segments had a significantly larger LI drop [19.8 (14.1-27.1) Ω] compared with segments with gaps [10.6 (7.8-14.7) Ω, P < 0.001). In view of left atrial wall thickness differences, the association between LI drop and block was further evaluated for anterior/roof and posterior/inferior segments. The optimal LI cut-off value for anterior/roof segments was 16.1 Ω (positive predictive value for block: 96.3%) and for posterior/inferior segments was 12.3 Ω (positive predictive value for block: 98.1%) where inter-lesion distances were ≤6 mm.
Conclusion
The magnitude of LI drop was predictive of acute PVI segment conduction block in patients with paroxysmal AF. The thinner posterior wall required smaller LI drops for block compared with the thicker anterior wall.

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

Europace: 17 Jul 2021; 23:1042-1051
Das M, Luik A, Shepherd E, Sulkin M, ... Ramos P, García-Bolao I
Europace: 17 Jul 2021; 23:1042-1051 | PMID: 33550380
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Abstract

Age-related tilt test responses in patients with suspected reflex syncope.

Rivasi G, Torabi P, Secco G, Ungar A, ... Brignole M, Fedorowski A
Aims
Tilt testing (TT) is recognized to be a valuable contribution to the diagnosis and the pathophysiology of vasovagal syncope (VVS). This study aimed to assess the influence of age on TT responses by examination of a large patient cohort.
Methods and results
Retrospective data from three experienced European Syncope Units were merged to include 5236 patients investigated for suspected VVS by the Italian TT protocol. Tilt testing-positivity rates and haemodynamics were analysed across age-decade subgroups. Of 5236 investigated patients, 3129 (60%) had a positive TT. Cardioinhibitory responses accounted for 16.5% of positive tests and were more common in younger patients, decreasing from the age of 50-59 years. Vasodepressor (VD) responses accounted for 24.4% of positive tests and prevailed in older patients, starting from the age of 50-59. Mixed responses (59.1% of cases) declined slightly with increasing age. Overall, TT positivity showed a similar age-related trend (P = 0.0001) and was significantly related to baseline systolic blood pressure (P < 0.001). Tilt testing was positive during passive phase in 18% and during nitroglycerine (TNG)-potentiated phase in 82% of cases. Positivity rate of passive phase declined with age (P = 0.001), whereas positivity rate during TNG remained quite stable. The prevalence of cardioinhibitory and VD responses was similar during passive and TNG-potentiated TT, when age-adjusted.
Conclusions
Age significantly impacts the haemodynamic pattern of TT responses, starting from the age of 50. Conversely, TT phase-passive or TNG-potentiated-does not significantly influence the type of response, when age-adjusted. Vagal hyperactivity dominates in younger patients, older patients show tendency to vasodepression.

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

Europace: 17 Jul 2021; 23:1100-1105
Rivasi G, Torabi P, Secco G, Ungar A, ... Brignole M, Fedorowski A
Europace: 17 Jul 2021; 23:1100-1105 | PMID: 33564843
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Abstract

Use of high-density activation and voltage mapping in combination with entrainment to delineate gap-related atrial tachycardias post atrial fibrillation ablation.

Vlachos K, Efremidis M, Derval N, Martin CA, ... Haïssaguerre M, Jaïs P
Aims
An incomplete understanding of the mechanism of atrial tachycardia (AT) is a major determinant of ablation failure. We systematically evaluated the mechanisms of AT using ultra-high-resolution mapping in a large cohort of patients.
Methods and results
We included 107 consecutive patients (mean age: 65.7 ± 9.2 years, males: 81 patients) with documented endocardial gap-related AT after left atrial ablation for persistent atrial fibrillation (AF). We analysed the mechanism of 134 AT (94 macro-re-entries and 40 localized re-entries) using high-resolution activation mapping in combination with high-density voltage and entrainment mapping. Voltage in the conducting channels may be extremely low, even <0.1 mV (0.14 ± 0.095 mV, 51 of 134 AT, 41%), and almost always <0.5 mV (0.03-0.5 mV, 133 of 134 AT, 99.3%). The use of multipolar Orion, HDGrid, and Pentaray catheters improved our accuracy in delineating ultra-low-voltage areas critical for maintenance of the circuit of endocardial gap-related AT. Conventional ablation catheters often do not detect any signal (noise level) even using adequate contact force, and only multipolar catheters of small electrodes and shorter interelectrode space can detect clear fractionated low-amplitude and high frequency signals, critical for re-entry maintenance. We performed a diagnosis in 112 out of 134 AT (83.6%) using only activation mapping and in 134 out of 134 AT (100%) using the combination of activation and entrainment mapping.
Conclusion 
High-resolution activation mapping in combination with high-density voltage and entrainment mapping is the ideal strategy to delineate the critical part of the circuit in endocardial gap-related re-entrant AT after 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: 17 Jul 2021; 23:1052-1062
Vlachos K, Efremidis M, Derval N, Martin CA, ... Haïssaguerre M, Jaïs P
Europace: 17 Jul 2021; 23:1052-1062 | PMID: 33564832
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Abstract

Relationship between procedural volume and complication rates for catheter ablation of atrial fibrillation: a systematic review and meta-analysis.

Tonchev IR, Nam MCY, Gorelik A, Kumar S, ... Kistler PM, Kalman JM
Aims
There are conflicting data as to the impact of procedural volume on outcomes with specific reference to the incidence of major complications after catheter ablation for atrial fibrillation. Questions regarding minimum volume requirements and whether these should be per centre or per operator remain unclear. Studies have reported divergent results. We performed a systematic review and meta-analysis of studies reporting the relationship between either operator or hospital atrial fibrillation (AF) ablation volumes and incidence of complications.
Methods and results
Databases were searched for studies describing the relationship between operator or hospital AF ablation volumes and incidence of complications which were published prior to 12 June 2020. Of 1593 articles identified, 14 (315 120 patients) were included in the meta-analysis. Almost two-thirds of the procedures were performed in low-volume centres. Both hospital volume of ≥50 and ≥100 procedures/year were associated with a significantly lower incidence of complications compared to <50/year (4.2% vs. 5.5%, OR = 0.58, 95% CI 0.50-0.66, P < 0.001) or <100/year (5.5% vs. 6.2%, OR = 0.62, 95% CI 0.53-0.73, P < 0.001), respectively. Hospitals performing ≥50 procedures/year demonstrated significantly lower mortality compared with those performing <50 procedures/year (0.16% vs. 0.55%, OR = 0.33, 95% CI 0.26-0.43, P < 0.001). A similar relationship existed between proceduralist volume of <50/year and incidence of complications [3.75% vs. 12.73%, P < 0.001; OR = 0.27 (0.23-0.32)].
Conclusion
There is an inverse relationship between both hospital and proceduralist AF ablation volume and the incidence of complications. Implementation of minimum hospital and operator AF ablation volume standards should be considered in the context of a broader strategy to identify AF ablation Centers of Excellence.

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

Europace: 17 Jul 2021; 23:1024-1032
Tonchev IR, Nam MCY, Gorelik A, Kumar S, ... Kistler PM, Kalman JM
Europace: 17 Jul 2021; 23:1024-1032 | PMID: 33595063
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Abstract

Bi-atrial high-density mapping reveals inhibition of wavefront turning and reduction of complex propagation patterns as main antiarrhythmic mechanisms of vernakalant.

van Hunnik A, Zeemering S, Podziemski P, Kuklik P, ... Verheule S, Schotten U
Aims
Complex propagation patterns are observed in patients and models with stable atrial fibrillation (AF). The degree of this complexity is associated with AF stability. Experimental work suggests reduced wavefront turning as an important mechanism for widening of the excitable gap. The aim of this study was to investigate how sodium channel inhibition by vernakalant affects turning behaviour and propagation patterns during AF.
Methods and results
Two groups of 8 goats were instrumented with electrodes on the left atrium, and AF was maintained by burst pacing for 3 or 22 weeks. Measurements were performed at baseline and two dosages of vernakalant. Unipolar electrograms were mapped (249 electrodes/array) on the left and right atrium in an open-chest experiment. Local activation times and conduction vectors, flow lines, the number of fibrillation waves, and local re-entries were determined. At baseline, fibrillation patterns contained numerous individual fibrillation waves conducting in random directions. Vernakalant induced conduction slowing and cycle length prolongation and terminated AF in 13/15 goats. Local re-entries were strongly reduced. Local conduction vectors showed increased preferential directions and less beat-to-beat variability. Breakthroughs and waves were significantly reduced in number. Flow line curvature reduced and waves conducted more homogenously in one direction. Overall, complex propagation patterns were strongly reduced. No substantial differences in drug effects between right and left atria or between goats with different AF durations were observed.
Conclusions
Destabilization of AF by vernakalant is associated with a lowering of fibrillation frequency and inhibition of complex propagation patterns, wave turning, local re-entries, and breakthroughs.

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

Europace: 17 Jul 2021; 23:1114-1123
van Hunnik A, Zeemering S, Podziemski P, Kuklik P, ... Verheule S, Schotten U
Europace: 17 Jul 2021; 23:1114-1123 | PMID: 33608723
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Impact:
Abstract

Current perspectives on wearable rhythm recordings for clinical decision-making: the wEHRAbles 2 survey.

Manninger M, Zweiker D, Svennberg E, Chatzikyriakou S, ... Potpara T, Duncker D
Novel wearable devices for heart rhythm analysis using either photoplethysmography (PPG) or electrocardiogram (ECG) are in daily clinical practice. This survey aimed to assess impact of these technologies on physicians\' clinical decision-making and to define, how data from these devices should be presented and integrated into clinical practice. The online survey included 22 questions, focusing on the diagnosis of atrial fibrillation (AF) based on wearable rhythm device recordings, suitable indications for wearable rhythm devices, data presentation and processing, reimbursement, and future perspectives. A total of 539 respondents {median age 38 [interquartile range (IQR) 34-46] years, 29% female} from 51 countries world-wide completed the survey. Whilst most respondents would diagnose AF (83%), fewer would initiate oral anticoagulation therapy based on a single-lead ECG tracing. Significantly fewer still (27%) would make the diagnosis based on PPG-based tracing. Wearable ECG technology is acceptable for the majority of respondents for screening, diagnostics, monitoring, and follow-up of arrhythmia patients, while respondents were more reluctant to use PPG technology for these indications. Most respondents (74%) would advocate systematic screening for AF using wearable rhythm devices, starting at patients\' median age of 60 (IQR 50-65) years. Thirty-six percent of respondents stated that there is no reimbursement for diagnostics involving wearable rhythm devices in their countries. Most respondents (56.4%) believe that costs of wearable rhythm devices should be shared between patients and insurances. Wearable single- or multiple-lead ECG technology is accepted for multiple indications in current clinical practice and triggers AF diagnosis and treatment. The unmet needs that call for action are reimbursement plans and integration of wearable rhythm device data into patient\'s files and hospital information systems.

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

Europace: 17 Jul 2021; 23:1106-1113
Manninger M, Zweiker D, Svennberg E, Chatzikyriakou S, ... Potpara T, Duncker D
Europace: 17 Jul 2021; 23:1106-1113 | PMID: 33842972
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Impact:
Abstract

Likelihood of injury due to vasovagal syncope: a systematic review and meta-analysis.

Jorge JG, Raj SR, Teixeira PS, Teixeira JAC, Sheldon RS
Aims
Vasovagal syncope (VVS) is the most common type of syncope and is usually considered a benign disorder. The potential for injury is worrisome but the likelihood is unknown. We aimed to determine the proportion of patients injured due to VVS.
Methods and results
A systematic search of studies published until August 2020 was performed in multiple medical and nursing databases. Included studies had data on the proportion of patients with injury due to VVS prior to study enrolment. Random effects methods were used. Twenty-three studies having 3593 patients met inclusion criteria. Patients were diagnosed clinically with VVS, and 82% had >2 syncopal episodes before enrolment. Tilt test was positive in 60% and 14 studies reported comorbidities (32.6% hypertensive). The weighted mean injury rate was 33.5% [95% confidence interval (CI): 27.3-40.5%]. The likelihood of injury correlated with population age (r = 0.4, P = 0.05), but not with sex, positive tilt test, or hypertension. The injury rates were 25.7% (95% CI: 19.1-32.8%) in studies with younger patients (mean age ≤50 years, n = 1803) and 43.4% (95% CI: 34.9-52.3%) in studies with older patients (P = 0.002). Nine studies reported major injuries; with a weighted mean rate of major injuries of 13.9% (95% CI: 9.5-19.8%).
Conclusion 
Injuries due to syncope are frequent, occurring in 33% of patients with VVS. The risk of major injuries is substantial. Older patients are at higher risk. Clinicians should be aware of the risk of injuries when providing care and advice to patients with VVS.

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

Europace: 17 Jul 2021; 23:1092-1099
Jorge JG, Raj SR, Teixeira PS, Teixeira JAC, Sheldon RS
Europace: 17 Jul 2021; 23:1092-1099 | PMID: 33693816
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Impact:
Abstract

Cryoballoon ablation vs. antiarrhythmic drugs: first-line therapy for patients with paroxysmal atrial fibrillation.

Kuniss M, Pavlovic N, Velagic V, Hermida JS, ... Chierchia GB, Cryo-FIRST Investigators
Aims
Treatment guidelines for patients with atrial fibrillation (AF) suggest that patients should be managed with an antiarrhythmic drug (AAD) before undergoing catheter ablation (CA). This study evaluated whether pulmonary vein isolation employing cryoballoon CA is superior to AAD therapy for the prevention of atrial arrhythmia (AA) recurrence in rhythm control naive patients with paroxysmal AF (PAF).
Methods and results
A total of 218 treatment naive patients with symptomatic PAF were randomized (1 : 1) to cryoballoon CA (Arctic Front Advance, Medtronic) or AAD (Class I or III) and followed for 12 months. The primary endpoint was ≥1 episode of recurrent AA (AF, atrial flutter, or atrial tachycardia) >30 s after a prespecified 90-day blanking period. Secondary endpoints included the rate of serious adverse events (SAEs) and recurrence of symptomatic palpitations (evaluated via patient diaries). Freedom from AA was achieved in 82.2% of subjects in the cryoballoon arm and 67.6% of subjects in the AAD arm (HR = 0.48, P = 0.01). There were no group differences in the time-to-first (HR = 0.76, P = 0.28) or overall incidence [incidence rate ratio (IRR)=0.79, P = 0.28] of SAEs. The incidence rate of symptomatic palpitations was lower in the cryoballoon (7.61 days/year) compared with the AAD arm (18.96 days/year; IRR = 0.40, P < 0.001).
Conclusions
Cryoballoon CA was superior to AAD therapy, significantly reducing AA recurrence in treatment naive patients with PAF. Additionally, cryoballoon CA was associated with lower symptom recurrence and a similar rate of SAEs compared with AAD therapy.

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

Europace: 17 Jul 2021; 23:1033-1041
Kuniss M, Pavlovic N, Velagic V, Hermida JS, ... Chierchia GB, Cryo-FIRST Investigators
Europace: 17 Jul 2021; 23:1033-1041 | PMID: 33728429
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Impact:
Abstract

Smartphone electrocardiogram for detecting atrial fibrillation after a cerebral ischaemic event: a multicentre randomized controlled trial.

Koh KT, Law WC, Zaw WM, Foo DHP, ... Fong AYY, Ong TK
Aims
Atrial fibrillation (AF) is a preventable cause of ischaemic stroke but it is often undiagnosed and undertreated. The utility of smartphone electrocardiogram (ECG) for the detection of AF after ischaemic stroke is unknown. The aim of this study is to determine the diagnostic yield of 30-day smartphone ECG recording compared with 24-h Holter monitoring for detecting AF ≥30 s.
Methods and results
In this multicentre, open-label study, we randomly assigned 203 participants to undergo one additional 24-h Holter monitoring (control group, n = 98) vs. 30-day smartphone ECG monitoring (intervention group, n = 105) using KardiaMobile (AliveCor®, Mountain View, CA, USA). Major inclusion criteria included age ≥55 years old, without known AF, and ischaemic stroke or transient ischaemic attack (TIA) within the preceding 12 months. Baseline characteristics were similar between the two groups. The index event was ischaemic stroke in 88.5% in the intervention group and 88.8% in the control group (P = 0.852). AF lasting ≥30 s was detected in 10 of 105 patients in the intervention group and 2 of 98 patients in the control group (9.5% vs. 2.0%; absolute difference 7.5%; P = 0.024). The number needed to screen to detect one AF was 13. After the 30-day smartphone monitoring, there was a significantly higher proportion of patients on oral anticoagulation therapy at 3 months compared with baseline in the intervention group (9.5% vs. 0%, P = 0.002).
Conclusions
Among patients ≥55 years of age with a recent cryptogenic stroke or TIA, 30-day smartphone ECG recording significantly improved the detection of AF when compared with the standard repeat 24-h Holter monitoring.

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

Europace: 17 Jul 2021; 23:1016-1023
Koh KT, Law WC, Zaw WM, Foo DHP, ... Fong AYY, Ong TK
Europace: 17 Jul 2021; 23:1016-1023 | PMID: 33782701
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Impact:
Abstract

CarDiac magnEtic Resonance for prophylactic Implantable-cardioVerter defibrillAtor ThErapy in Non-Ischaemic dilated CardioMyopathy: an international Registry.

Guaricci AI, Masci PG, Muscogiuri G, Guglielmo M, ... Schwitter J, Pontone G
Aims
The aim of this registry was to evaluate the additional prognostic value of a composite cardiac magnetic resonance (CMR)-based risk score over standard-of-care (SOC) evaluation in a large cohort of consecutive unselected non-ischaemic cardiomyopathy (NICM) patients.
Methods and results
In the DERIVATE registry (www.clinicaltrials.gov/registration: RCT#NCT03352648), 1000 (derivation cohort) and 508 (validation cohort) NICM patients with chronic heart failure (HF) and left ventricular ejection fraction <50% were included. All-cause mortality and major adverse arrhythmic cardiac events (MAACE) were the primary and secondary endpoints, respectively. During a median follow-up of 959 days, all-cause mortality and MAACE occurred in 72 (7%) and 93 (9%) patients, respectively. Age and >3 segments with midwall fibrosis on late gadolinium enhancement (LGE) were the only independent predictors of all-cause mortality (HR: 1.036, 95% CI: 1.0117-1.056, P < 0.001 and HR: 2.077, 95% CI: 1.211-3.562, P = 0.008, respectively). For MAACE, the independent predictors were male gender, left ventricular end-diastolic volume index by CMR (CMR-LVEDVi), and >3 segments with midwall fibrosis on LGE (HR: 2.131, 95% CI: 1.231-3.690, P = 0.007; HR: 3.161, 95% CI: 1.750-5.709, P < 0.001; and HR: 1.693, 95% CI: 1.084-2.644, P = 0.021, respectively). A composite clinical and CMR-based risk score provided a net reclassification improvement of 63.7% (P < 0.001) for MAACE occurrence when added to the model based on SOC evaluation. These findings were confirmed in the validation cohort.
Conclusion
In a large multicentre, multivendor cohort registry reflecting daily clinical practice in NICM work-up, a composite clinical and CMR-based risk score provides incremental prognostic value beyond SOC evaluation, which may have impact on the indication of implantable cardioverter-defibrillator implantation.

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

Europace: 17 Jul 2021; 23:1072-1083
Guaricci AI, Masci PG, Muscogiuri G, Guglielmo M, ... Schwitter J, Pontone G
Europace: 17 Jul 2021; 23:1072-1083 | PMID: 33792661
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Impact:
Abstract

Sex differences in disease progression and arrhythmic risk in patients with arrhythmogenic cardiomyopathy.

Rootwelt-Norberg C, Lie ØH, Chivulescu M, Castrini AI, ... Edvardsen T, Haugaa KH
Aims
We aimed to assess sex-specific phenotypes and disease progression, and their relation to exercise, in arrhythmogenic cardiomyopathy (AC) patients.
Methods and results
In this longitudinal cohort study, we included consecutive patients with AC from a referral centre. We performed echocardiography at baseline and repeatedly during follow-up. Patients\' exercise dose at inclusion was expressed as metabolic equivalents of task (MET)-h/week. Ventricular arrhythmia (VA) was defined as aborted cardiac arrest, sustained ventricular tachycardia, or appropriate therapy by implantable cardioverter-defibrillator. We included 190 AC patients (45% female, 51% probands, age 41 ± 17 years). Ventricular arrhythmia had occurred at inclusion or occurred during follow-up in 85 patients (33% of females vs. 55% of males, P = 0.002). Exercise doses were higher in males compared with females [25 (interquartile range, IQR 14-51) vs. 12 (IQR 7-22) MET-h/week, P < 0.001]. Male sex was a marker of proband status [odds ratio (OR) 2.6, 95% confidence interval (CI) 1.4-5.0, P = 0.003] and a marker of VA (OR 2.6, 95% CI 1.4-5.0, P = 0.003), but not when adjusted for exercise dose and age (adjusted OR 1.8, 95% CI 0.9-3.6, P = 0.12 and 1.5, 95% CI 0.7-3.1, P = 0.30, by 5 MET-h/week increments). In all, 167 (88%) patients had ≥2 echocardiographic examinations during 6.9 (IQR 4.7-9.8) years of follow-up. We observed no sex differences in deterioration of right or left ventricular dimensions and functions.
Conclusion
Male AC patients were more often probands and had higher prevalence of VA than female patients, but not when adjusting for exercise dose. Importantly, disease progression was similar between male and female patients.

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

Europace: 17 Jul 2021; 23:1084-1091
Rootwelt-Norberg C, Lie ØH, Chivulescu M, Castrini AI, ... Edvardsen T, Haugaa KH
Europace: 17 Jul 2021; 23:1084-1091 | PMID: 33829244
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Impact:
Abstract

EHRA expert consensus statement and practical guide on optimal implantation technique for conventional pacemakers and implantable cardioverter-defibrillators: endorsed by the Heart Rhythm Society (HRS), the Asia Pacific Heart Rhythm Society (APHRS), and the Latin-American Heart Rhythm Society (LAHRS).

Burri H, Starck C, Auricchio A, Biffi M, ... Vassilikos VP, Martins Oliveira M
With the global increase in device implantations, there is a growing need to train physicians to implant pacemakers and implantable cardioverter-defibrillators. Although there are international recommendations for device indications and programming, there is no consensus to date regarding implantation technique. This document is founded on a systematic literature search and review, and on consensus from an international task force. It aims to fill the gap by setting standards for device implantation.

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

Europace: 17 Jul 2021; 23:983-1008
Burri H, Starck C, Auricchio A, Biffi M, ... Vassilikos VP, Martins Oliveira M
Europace: 17 Jul 2021; 23:983-1008 | PMID: 33878762
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Impact:
Abstract

The V6-V1 interpeak interval: a novel criterion for the diagnosis of left bundle branch capture.

Jastrzębski M, Burri H, Kiełbasa G, Curila K, ... Rajzer M, Vijayaraman P
Aims
We hypothesized that during left bundle branch (LBB) area pacing, the various possible combinations of direct capture/non-capture of the septal myocardium and the LBB result in distinct patterns of right and left ventricular activation. This could translate into different combinations of R-wave peak time (RWPT) in V1 and V6. Consequently, the V6-V1 interpeak interval could differentiate the three types of LBB area capture: non-selective (ns-)LBB, selective (s-)LBB, and left ventricular septal (LVS).
Methods and results
Patients with unquestionable evidence of LBB capture were included. The V6-V1 interpeak interval, V6RWPT, and V1RWPT were compared between different types of LBB area capture. A total of 468 patients from two centres were screened, with 124 patients (239 electrocardiograms) included in the analysis. Loss of LVS capture resulted in an increase in V1RWPT by ≥15 ms but did not impact V6RWPT. Loss of LBB capture resulted in an increase in V6RWPT by ≥15 ms but only minimally influenced V1RWPT. Consequently, the V6-V1 interval was longest during s-LBB capture (62.3 ± 21.4 ms), intermediate during ns-LBB capture (41.3 ± 14.0 ms), and shortest during LVS capture (26.5 ± 8.6 ms). The optimal value of the V6-V1 interval value for the differentiation between ns-LBB and LVS capture was 33 ms (area under the receiver operating characteristic curve of 84.7%). A specificity of 100% for the diagnosis of LBB capture was obtained with a cut-off value of >44 ms.
Conclusion
The V6-V1 interpeak interval is a promising novel criterion for the diagnosis of LBB area capture.

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

Europace: 11 Jul 2021; epub ahead of print
Jastrzębski M, Burri H, Kiełbasa G, Curila K, ... Rajzer M, Vijayaraman P
Europace: 11 Jul 2021; epub ahead of print | PMID: 34255038
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Impact:
Abstract

Pulsed field ablation prevents chronic atrial fibrotic changes and restrictive mechanics after catheter ablation for atrial fibrillation.

Nakatani Y, Sridi-Cheniti S, Cheniti G, Ramirez FD, ... Jaïs P, Cochet H
Aims
Pulsed field ablation (PFA), a non-thermal ablative modality, may show different effects on the myocardial tissue compared to thermal ablation. Thus, this study aimed to compare the left atrial (LA) structural and mechanical characteristics after PFA vs. thermal ablation.
Methods and results
Cardiac magnetic resonance was performed pre-ablation, acutely (<3 h), and 3 months post-ablation in 41 patients with paroxysmal atrial fibrillation (AF) undergoing pulmonary vein (PV) isolation with PFA (n = 18) or thermal ablation (n = 23, 16 radiofrequency ablations, 7 cryoablations). Late gadolinium enhancement (LGE), T2-weighted, and cine images were analysed. In the acute stage, LGE volume was 60% larger after PFA vs. thermal ablation (P < 0.001), and oedema on T2 imaging was 20% smaller (P = 0.002). Tissue changes were more homogeneous after PFA than after thermal ablation, with no sign of microvascular damage or intramural haemorrhage. In the chronic stage, the majority of acute LGE had disappeared after PFA, whereas most LGE persisted after thermal ablation. The maximum strain on PV antra, the LA expansion index, and LA active emptying fraction declined acutely after both PFA and thermal ablation but recovered at the chronic stage only with PFA.
Conclusion
Pulsed field ablation induces large acute LGE without microvascular damage or intramural haemorrhage. Most LGE lesions disappear in the chronic stage, suggesting a specific reparative process involving less chronic fibrosis. This process may contribute to a preserved tissue compliance and LA reservoir and booster pump functions.

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

Europace: 07 Jul 2021; epub ahead of print
Nakatani Y, Sridi-Cheniti S, Cheniti G, Ramirez FD, ... Jaïs P, Cochet H
Europace: 07 Jul 2021; epub ahead of print | PMID: 34240134
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Impact:
Abstract

Spatial characterization of the tachycardia circuit of atrioventricular nodal re-entrant tachycardia.

Katritsis DG, Marine JE, Katritsis G, Latchamsetty R, ... Sánchez-Quintana D, Anderson RH
Aims
The exact circuit of atrioventricular nodal re-entrant tachycardia (AVNRT) remains elusive. To assess the location and dimensions of the AVNRT circuit.
Methods and results
Both typical and atypical AVNRT were induced at electrophysiology study of 14 patients. We calculated the activation time of the fast and slow pathways, and consequently, the length of the slow pathway, by assuming an average conduction velocity of 0.04 mm/ms in the nodal area. The distance between the compact atrioventricular node and the slow pathway ablating electrode was measured on three-dimensionally reconstructed fluoroscopic images obtained in diastole and systole. We also measured the length of the histologically discrete right inferior nodal extension in 31 human hearts. The length of the slow pathway was calculated to be 10.8 ± 1.3 mm (range 8.2-12.8 mm). The distance from the node to the ablating electrode was measured in five patients 17.0 ± 1.6 mm (range 14.9-19.2 mm) and was consistently longer than the estimated length of the slow pathway (P < 0.001). The length of the right nodal inferior extension in histologic specimens was 8.1 ± 2.3 mm (range 5.3-13.7 mm). There were no statistically significant differences between these values and the calculated slow pathway lengths.
Conclusion
Successful ablation affects the tachycardia circuit without necessarily abolishing slow conduction, probably by interrupting the circuit at the septal isthmus.

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

Europace: 07 Jul 2021; epub ahead of print
Katritsis DG, Marine JE, Katritsis G, Latchamsetty R, ... Sánchez-Quintana D, Anderson RH
Europace: 07 Jul 2021; epub ahead of print | PMID: 34240123
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Impact:
Abstract

Clinical and electrophysiological predictors of device-detected new-onset atrial fibrillation during 3 years after cardiac surgery.

Bidar E, Zeemering S, Gilbers M, Isaacs A, ... Maessen JG, Schotten U
Aims
Postoperative atrial fibrillation (POAF) after cardiac surgery is an independent predictor of stroke and mortality late after discharge. We aimed to determine the burden and predictors of early (up to 5th postoperative day) and late (after 5th postoperative day) new-onset atrial fibrillation (AF) using implantable loop recorders (ILRs) in patients undergoing open chest cardiac surgery.
Methods and results
Seventy-nine patients without a history of AF undergoing cardiac surgery underwent peri-operative high-resolution mapping of electrically induced AF and were followed 36 months after surgery using an ILR (Reveal XT™). Clinical and electrophysiological predictors of late POAF were assessed. POAF occurred in 46 patients (58%), with early POAF detected in 27 (34%) and late POAF in 37 patients (47%). Late POAF episodes were short-lasting (mostly between 2 min and 6 h) and showed a circadian rhythm pattern with a peak of episode initiation during daytime. In POAF patients, electrically induced AF showed more complex propagation patterns than in patients without POAF. Early POAF, right atrial (RA) volume, prolonged PR time, and advanced age were independent predictors of late POAF.
Conclusions
Late POAF occurred in 47% of patients without a history of AF. Patients who develop early POAF, with higher age, larger RA, or prolonged PR time have a higher risk of developing late POAF and may benefit from intensified rhythm follow-up after cardiac surgery.
Clinicaltrials.gov number
NCT01530750.

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

Europace: 30 Jun 2021; epub ahead of print
Bidar E, Zeemering S, Gilbers M, Isaacs A, ... Maessen JG, Schotten U
Europace: 30 Jun 2021; epub ahead of print | PMID: 34198338
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Impact:
Abstract

The cost of non-response to cardiac resynchronization therapy: characterizing heart failure events following cardiac resynchronization therapy.

Varma N, Auricchio A, Connolly AT, Boehmer J, ... Nabutovsky Y, Gold M
Aims
The aim of this study is to quantify healthcare resource utilization among non-responders to cardiac resynchronization therapy (CRT-NR) by heart failure (HF) events and influence of comorbidities.
Methods and results
The ADVANCE CRT registry (2013-2015) prospectively identified responders/CRT-NRs 6 months post-implant using the clinical composite score. Heart failure event rates and associated cost, both overall and separated for inpatient hospitalizations, office visits, emergency room visits, and observational stays, were quantified. Costs of events were imputed from payments for similar real-world encounters in subjects with CRT-D/P devices in the MarketScan™ commercial and Medicare Supplemental insurance claims databases. Effects of patient demographics and comorbidities on event rates and cost were evaluated. Of 879 US patients (age 69 ± 11 years, 29% female, ischaemic disease 52%), 310 (35%) were CRT-NR. Among CRT-NRs vs. responders, more patients developed HF (41% vs. 11%, P < 0.001), HF event rate was higher (67.0 ± 21.7 vs. 11.4 ± 3.7/100 pt-year, P < 0.001), and HF readmission within 30 days was more common [hazard ratio 7.06, 95% confidence interval (2.1-43.7)]. Inpatient hospitalization was the most common and most expensive event type in CRT-NR. Comorbid HF was increased by diabetes, hypertension, and pulmonary disorders. Over 2 years, compared to CRT responders, each CRT-NR resulted in excess cost of $6388 ($3859-$10 483) to Medicare (P = 0.015) or $10 197 ($6161-$17 394) to private insurances (P = 0.014).
Conclusion
Healthcare expenditures associated with contemporary CRT non-response management are among the highest for any HF patient group. This illustrates an unmet need for interventions to improve HF outcomes and reduce costs among some CRT recipients.

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

Europace: 30 Jun 2021; epub ahead of print
Varma N, Auricchio A, Connolly AT, Boehmer J, ... Nabutovsky Y, Gold M
Europace: 30 Jun 2021; epub ahead of print | PMID: 34198334
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Impact:
Abstract

Novel electrocardiographic criteria for short QT syndrome in children and adolescents.

Suzuki H, Horie M, Ozawa J, Sumitomo N, ... Akazawa K, Nagashima M
Aims
Although shortening of the corrected QT interval (QTc) is a key finding in the diagnosis of short QT syndrome (SQTS), there may be overlap of the QTc between SQTS patients and normal subjects in childhood and adolescence. We aimed to investigate electrocardiographic findings for differentiation of SQTS patients.
Methods and results
The SQTS group comprised 34 SQTS patients <20 years old, including 9 from our institutions and 25 from previous reports. The control group comprised 61 apparently healthy subjects with an QTc of <360 ms who were selected from 13 314 participants in a school-based screening programme. We compared electrocardiographic findings, including QT and Jpoint-Tpeak intervals (QT and J-Tpeak, respectively), those corrected by using the Bazett\'s and Fridericia\'s formulae (cB and cF, respectively) and early repolarization (ER) between the groups. QT, QTc by using Bazett\'s formula (QTcB), QTc by using Fridericia\'s formula (QTcF), J-Tpeak, J-Tpeak cB, and J-Tpeak cF were significantly shorter in the SQTS group than in the control group. On receiver operating characteristic curve analysis, the area under the curve (AUC) was largest for QTcB (0.888) among QT, QTcB, and QTcF, with a cut-off value of 316 ms (sensitivity: 79.4% and specificity: 96.7%). The AUC was largest for J-Tpeak cB (0.848) among J-Tpeak, J-Tpeak cB, and J-Tpeak cF, with a cut-off value of 181 ms (sensitivity: 80.8% and specificity: 91.8%). Early repolarization was found more frequently in the SQTS group than in the control group (67% vs. 23%, P = 0.001).
Conclusion
A QTcB <316 ms, J-Tpeak cB < 181 ms, and the presence of ER may indicate SQTS patients in childhood and adolescence.

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

Europace: 27 Jun 2021; epub ahead of print
Suzuki H, Horie M, Ozawa J, Sumitomo N, ... Akazawa K, Nagashima M
Europace: 27 Jun 2021; epub ahead of print | PMID: 34179980
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Impact:
Abstract

Epidemiology of cardiac implantable electronic device infections: incidence and risk factors.

Han HC, Hawkins NM, Pearman CM, Birnie DH, Krahn AD
Cardiac implantable electronic device (CIED) infection is a potentially devastating complication of CIED procedures, causing significant morbidity and mortality for patients. Of all CIED complications, infection has the greatest impact on mortality, requirement for re-intervention and additional hospital treatment days. Based on large prospective studies, the infection rate at 12-months after a CIED procedure is approximately 1%. The risk of CIED infection may be related to several factors which should be considered with regards to risk minimization. These include technical factors, patient factors, and periprocedural factors. Technical factors include the number of leads and size of generator, the absolute number of interventions which have been performed for the patient, and the operative approach. Patient factors include various non-modifiable underlying comorbidities and potentially modifiable transient conditions. Procedural factors include both peri-operative and post-operative factors. The contemporary PADIT score, derived from a large cohort of CIED patients, is useful for the prediction of infection risk. In this review, we summarize the key information regarding epidemiology, incidence and risk factors for CIED infection.

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

Europace: 22 Jun 2021; 23:iv3-iv10
Han HC, Hawkins NM, Pearman CM, Birnie DH, Krahn AD
Europace: 22 Jun 2021; 23:iv3-iv10 | PMID: 34051086
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Impact:
Abstract

Infections associated with cardiac electronic implantable devices: economic perspectives and impact of the TYRX™ antibacterial envelope.

Boriani G, Vitolo M, Wright DJ, Biffi M, ... Tarakji KG, Wilkoff BL
The occurrence of cardiac implantable electronic devices (CIED) infections and related adverse outcomes have an important financial impact on the healthcare system, with hospitalization length of stay (2-3 weeks on average) being the largest cost driver, including the cost of device system extraction and device replacement accounting for more than half of total costs. In the recent literature, the economic profile of the TYRX™ absorbable antibacterial envelope was analysed taking into account both randomized and non-randomized trial data. Economic analysis found that the envelope is associated with cost-effectiveness ratios below USA and European benchmarks in selected patients at increased risk of infection. Therefore, the TYRX™ envelope, by effectively reducing CIED infections, provides value according to the criteria of affordability currently adopted by USA and European healthcare systems.

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

Europace: 22 Jun 2021; 23:iv33-iv44
Boriani G, Vitolo M, Wright DJ, Biffi M, ... Tarakji KG, Wilkoff BL
Europace: 22 Jun 2021; 23:iv33-iv44 | PMID: 34160600
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Impact:
Abstract

Therapy and outcomes of cardiac implantable electronic devices infections.

Perrin T, Deharo JC
Cardiac implantable electronic device (CIED) infection causes significant morbidity and mortality without appropriate treatment. It can present as incisional infection, pocket infection, systemic CIED infection, or occult bacteraemia. Complete percutaneous CIED extraction (excepted in case of incisional infection) and appropriate antibiotic therapy are the two main pillars of therapy. Device reimplantation, if needed, should be delayed sufficiently to allow control of the infection. Here, we address the differences in prognosis according to the clinical scenario and the different treatment options.

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

Europace: 22 Jun 2021; 23:iv20-iv27
Perrin T, Deharo JC
Europace: 22 Jun 2021; 23:iv20-iv27 | PMID: 34160599
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Impact:
Abstract

Antibiotic eluting envelopes: evidence, technology, and defining high-risk populations.

Callahan TD, Tarakji KG, Wilkoff BL
Cardiovascular implantable electronic devices (CIED) are effective and important components of modern cardiovascular care. Despite the dramatic improvements in the functionality and reliability of these devices, over time patients are at risk for developing several morbidities, the most feared of which are local and systemic infections. Despite significant financial investment and aggressive therapy with hospitalization, intravenous antibiotics, and transvenous lead extraction, the outcomes include a 1-year mortality rate as high as 25%. This risk of infection has increased over time, likely due to the increased complexity of the surgical interventions required to insert and replace these devices. The only way to reduce this morbidity and mortality is to prevent these infections, and other than preoperative antibiotics, there were little data supporting effective therapy until the WRAP-IT trial provided randomized data showing that pocket infections can be reduced by 60% at 12 months and major CIED infections reduced by 40% at 1 year with the use of the absorbable antibiotic eluting envelope in patient CIED procedures at high risk of infection. Not all CIED procedures are at high risk of infection and justify the use of the envelope, but cost-effectiveness data support the use of the antibiotic envelope particularly in patients with defibrillator replacements, revisions, and upgrades, such as to a resynchronization device and in patients with prior CIED infection, history of immunocompromise, two or more prior procedures, or a history of renal dysfunction.

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

Europace: 22 Jun 2021; 23:iv28-iv32
Callahan TD, Tarakji KG, Wilkoff BL
Europace: 22 Jun 2021; 23:iv28-iv32 | PMID: 34160597
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Abstract

How does the level of pulmonary venous isolation compare between pulsed field ablation and thermal energy ablation (radiofrequency, cryo, or laser)?

Kawamura I, Neuzil P, Shivamurthy P, Kuroki K, ... Koruth JS, Reddy VY
Aims
We studied the extent/area of electrical pulmonary vein isolation (PVI) after either pulsed field ablation (PFA) using a pentaspline catheter or thermal ablation technologies.
Methods and results
In a clinical trial (NCT03714178), paroxysmal atrial fibrillation (PAF) patients underwent PVI with a multi-electrode pentaspline PFA catheter using a biphasic waveform, and after 75 days, detailed voltage maps were created during protocol-specified remapping studies. Comparative voltage mapping data were retrospectively collected from consecutive PAF patients who (i) underwent PVI using thermal energy, (ii) underwent reablation for recurrence, and (iii) had durably isolated PVs. The left and right PV antral isolation areas and non-ablated posterior wall were quantified. There were 20 patients with durable PVI in the PFA cohort, and 39 in the thermal ablation cohort [29 radiofrequency ablation (RFA), 6 cryoballoon, and 4 visually guided laser balloon]. Pulsed field ablation patients were younger with shorter follow-up. Left atrial diameter and ventricular systolic function were preserved in both cohorts. There was no significant difference between the PFA and thermal ablation cohorts in either the left- and right-sided PV isolation areas, or the non-ablated posterior wall area. The right superior PV isolation area was smaller with PFA than RFA, but this disappeared after propensity score matching. Notch-like normal voltage areas were seen at the posterior aspect of the carina in the balloon sub-cohort, but not the PFA or RFA cohorts.
Conclusion
Catheter-based PVI with the pentaspline PFA catheter creates chronic PV antral isolation areas as encompassing as thermal energy ablation.

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

Europace: 20 Jun 2021; epub ahead of print
Kawamura I, Neuzil P, Shivamurthy P, Kuroki K, ... Koruth JS, Reddy VY
Europace: 20 Jun 2021; epub ahead of print | PMID: 34151947
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Impact:
Abstract

First-line treatment of persistent and long-standing persistent atrial fibrillation with single-stage hybrid ablation: a 2-year follow-up study.

Magni FT, Al-Jazairi MIH, Mulder BA, Klinkenberg T, ... Mariani MA, Blaauw Y
Aims
This study evaluates the efficacy and safety of first-line single-stage hybrid ablation of (long-standing) persistent atrial fibrillation (AF), over a follow-up period of 2 years, and provides additional information on arrhythmia recurrences and electrophysiological findings at repeat ablation.
Methods and results
This is a prospective cohort study that included 49 patients (65% persistent AF; 35% long-standing persistent AF) who underwent hybrid ablation as first-line ablation treatment (no previous endocardial ablation). Patients were relatively young (57.0 ± 8.5 years) and predominantly male (89.8%). Median CHA2DS2-VASc score was 1.0 (0.5; 2.0) and mean left atrium volume index was 43.7 ± 10.9 mL/m2. Efficacy was assessed by 12-lead electrocardiography and 72-h Holter monitoring after 3, 6, 12, and 24 months. Recurrence was defined as AF/atrial flutter (AFL)/tachycardia (AT) recorded by electrocardiography or Holter monitoring lasting >30 s during 2-year follow-up. At 2-year follow-up, single and multiple procedure success rates were 67% and 82%, respectively. Two (4%) patients experienced a major complication (bleeding) requiring intervention following hybrid ablation. Among the 16 (33%) patients who experienced an AF/AFL/AT recurrence, 13 (81%) were ATs/AFLs and only 3 (19%) were AF. Repeat ablation was performed in 10 (20%) patients and resulted in sinus rhythm in 7 (70%) at 2-year follow-up.
Conclusion
First-line single-stage hybrid AF ablation is an effective treatment strategy for patients with persistent and long-standing persistent AF with an acceptable rate of major complications. Recurrences are predominantly AFL/AT that can be successfully ablated percutaneously. Hybrid ablation seems a feasible approach for first-line ablation of (long-standing) persistent AF.

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

Europace: 17 Jun 2021; epub ahead of print
Magni FT, Al-Jazairi MIH, Mulder BA, Klinkenberg T, ... Mariani MA, Blaauw Y
Europace: 17 Jun 2021; epub ahead of print | PMID: 34143871
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Impact:
Abstract

Cardiac magnetic resonance to predict recurrences after ventricular tachycardia ablation: septal involvement, transmural channels, and left ventricular mass.

Quinto L, Sanchez P, Alarcón F, Garre P, ... Mont L, Roca-Luque I
Aims
Ventricular tachycardia (VT) substrate-based ablation has an increasing role in patients with structural heart disease-related VT. VT is linked to re-entry in relation to myocardial scarring with areas of conduction block (core scar) and areas of slow conduction [border zone (BZ)]. VT substrate can be analysed by late gadolinium enhancement cardiac magnetic resonance (LGE-CMR). Our study aims to analyse the role of LGE-CMR in identifying predictors of VT recurrence after ablation.
Methods and results
We analysed 110 consecutive patients who underwent VT ablation from 2013 to 2018. All patients underwent a preprocedural LGE-CMR, and in 94 patients (85.5%), the CMR was used to aid the ablation. All LGE-CMR images were semi-automatically processed using dedicated software to detect scarring and conducting channels. After a median follow-up of 2.7 ± 1.6 years, the overall VT recurrence was 41.8% with an implantable cardioverter-defibrillator shock reduction from 43.6% to 28.2% before and after ablation, respectively. The amount of BZ (26.6 ± 13.9 vs. 19.6 ± 9.7 g, P = 0.012), the total amount of scarring (37.1 ± 18.2 vs. 29 ± 16.3 g, P = 0,033), and left ventricular (LV) mass (168.3 ± 53.3 vs. 152.3 ± 46.4 g, P < 0.001) were associated with VT recurrence. LGE septal distribution [62.5% vs. 37.8%; hazard ratio (HR) 1.67 (1.02-3.93), P = 0.044], channels with transmural path [66.7% vs. 31.4%, HR 3.25 (1.70-6.23), P < 0.001], and midmural channels [54.3% vs. 27.6%, HR 2.49 (1.21-5.13), P = 0.013] were related with VT recurrence. Multivariate analysis showed that the presence of septal LGE [HR 3.67 (1.60-8.38), P = 0.002], transmural channels [HR 2.32 (1.15-4.72), P = 0.019], and LV mass [HR 1.01 (1.005-1.019), P = 0.002] were independent predictors of VT recurrence.
Conclusion
Pre-procedural LGE-CMR is a helpful and feasible technique to identify patients with high risk of VT recurrence after ablation. LV mass, septal LGE distribution, and transmural channels were predictive factors of post-ablation VT recurrence.

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

Europace: 17 Jun 2021; epub ahead of print
Quinto L, Sanchez P, Alarcón F, Garre P, ... Mont L, Roca-Luque I
Europace: 17 Jun 2021; epub ahead of print | PMID: 34142121
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Impact:
Abstract

Prognostic markers of all-cause mortality in patients with atrial fibrillation: data from the prospective long-term registry of the German Atrial Fibrillation NETwork (AFNET).

Nabauer M, Oeff M, Gerth A, Wegscheider K, ... Breithardt G, Steinbeck G
Aims
Atrial fibrillation (AF) is associated with a high risk of cardiovascular and non-cardiovascular death, even on anticoagulation. It is controversial, which conditions-including concomitant diseases and AF itself-contribute to this mortality. To further clarify these questions, major determinants of long-term mortality and their contribution to death were quantified in an unselected cohort of AF patients.
Methods and results
We established a large nationwide registry comprising 8833 AF-patients with a median follow-up of 6.5 years (45 345 patient-years) and central adjudication of adverse events. Baseline characteristics of the patients were evaluated as predictors of mortality using Cox regression and C-indices for determination of predictive power. Annualized mortality was highest in the first year (6.2%) and remained high thereafter (5.2% in men and 5.5% in women). Thirty-eight percent of all deaths were cardiovascular, mainly due to heart failure or sudden death. Sex-specific age was the strongest predictor of mortality, followed by concomitant cardiovascular and non-cardiovascular conditions. These factors accounted for 25% of the total mortality beyond age and sex and for 84% of the mortality differences between AF types. Thus, the electrical phenotype of the disease at baseline contributed only marginally to prediction of mortality.
Conclusion
Mortality is high in AF patients and arises primarily from heart failure, peripheral artery disease, chronic obstructive lung disease, chronic kidney disease, and diabetes mellitus, which, therefore, should be targeted to lower mortality. Parameters related to the electrical manifestation of AF did not have an independent impact on long-term mortality in our representative cohort.

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

Europace: 16 Jun 2021; epub ahead of print
Nabauer M, Oeff M, Gerth A, Wegscheider K, ... Breithardt G, Steinbeck G
Europace: 16 Jun 2021; epub ahead of print | PMID: 34136917
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Abstract

The β-angle can help guide clinical decisions in the diagnostic work-up of patients suspected of Brugada syndrome: a validation study of the β-angle in determining the outcome of a sodium channel provocation test.

van der Ree MH, Vendrik J, Verstraelen TE, Kors JA, ... Tan HL, Postema PG
Aims
In patients with Brugada syndrome (BrS) but without spontaneous Type-1 electrocardiogram, several electrocardiographic characteristics have been studied, including the β-angle. Previous studies suggested that the β-angle might be useful in distinguishing BrS-patients from patients with only suggestive repolarization patterns without performing sodium channel blocker provocation testing. In this study, we aimed to determine the diagnostic value of the β-angle in patients suspected of BrS.
Methods and results
A large cohort (n = 1430) of consecutive patients who underwent provocation testing was evaluated. β-angles were measured in leads V1, V2, and their corresponding positions over the second and third intercostal space. Receiver-operating characteristic curves were constructed and the diagnostic accuracy of previously reported β-angle cut-offs were calculated and evaluated. The importance of the β-angle for predicting the provocation test outcome was determined using a prediction model constructed with logistic regression. The optimum β-angle cut-off in our cohort for ruling out a positive provocation test was 15°; sensitivities were 80-98% and negative predictive values were 79-96% among the right precordial leads. Previously reported β-angle cut-offs performed less well, indicated by lower Youden indices. In the optimism-corrected prediction model [C-statistic: 0.78 (95% CI: 0.75-0.81)], the β-angle had large value (Z-score: 2.1-10.3) and aided construction of a nomogram to predict test outcome.
Conclusion
To predict the outcome of provocation testing for BrS, the β-angle alone does not demonstrate strong diagnostic characteristics. However, the β-angle is an important variable to predict provocation test outcome and thus has added value.

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

Europace: 13 Jun 2021; epub ahead of print
van der Ree MH, Vendrik J, Verstraelen TE, Kors JA, ... Tan HL, Postema PG
Europace: 13 Jun 2021; epub ahead of print | PMID: 34125232
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Abstract

The Atrial Fibrillation Better Care pathway for managing atrial fibrillation: a review.

Stevens D, Harrison SL, Kolamunnage-Dona R, Lip GYH, Lane DA
The 2020 European Society of Cardiology guidelines endorse the Atrial Fibrillation Better Care (ABC) pathway as a structured approach for the management of atrial fibrillation (AF), addressing three principal elements: \'A\' - avoid stroke (with oral anticoagulation), \'B\' - patient-focused better symptom management, and \'C\' - cardiovascular and comorbidity risk factor reduction and management. This review summarizes the definitions used for the ABC criteria in different studies and the impact of adherence/non-adherence on clinical outcomes, from 12 studies on seven different cohorts. All studies consistently showed statistically significant reductions in the risk of stroke, myocardial infarction, and mortality among those with ABC pathway adherent treatment. The ABC pathway provides a simple decision-making framework to enable consistent equitable care from clinicians in primary and secondary/tertiary care. Further research examining the impact of ABC pathway implementation in prospective cohorts utilizing consistent inclusion criteria and definitions of \'A\', \'B\', and \'C\' adherent care is warranted.

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

Europace: 13 Jun 2021; epub ahead of print
Stevens D, Harrison SL, Kolamunnage-Dona R, Lip GYH, Lane DA
Europace: 13 Jun 2021; epub ahead of print | PMID: 34125202
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Impact:
Abstract

Predictors of sinus rhythm 6 weeks after cardioversion of atrial fibrillation: a pre-planned post hoc analysis of the X-VeRT trial.

Cappato R, Ezekowitz MD, Hohnloser SH, Meng IL, Wosnitza M, Camm AJ
Aims
Using a pre-planned post hoc analysis of patients included in X-VeRT, we evaluated predictors of sinus rhythm at 6 weeks after planned cardioversion.
Methods and results
Receiver operating characteristic curves and logistic regression models were used to evaluate continuous and categorical variables as predictors of sinus rhythm 6 at weeks from cardioversion (end of study). The primary analysis was performed in successfully cardioverted patients with an evaluable electrocardiogram at end of study. A second analysis evaluated additional patients who spontaneously restored sinus rhythm before planned cardioversion. Of the 1504 patients with atrial fibrillation of >48 h or of unknown duration who were randomly assigned to either rivaroxaban or vitamin K antagonist, 1039 (64.6 ± 10.3 years, 73.4% male) underwent planned cardioversion and were included in this study. Patients receiving early cardioversion (i.e. between 1 and 5 days from hospitalization) had a 67% higher probability to have sinus rhythm at end of study than those who received delayed cardioversion (i.e. between 21 and 56 days from hospitalization) [odds ratio (OR) 1.67, confidence interval (CI) 1.27-2.18; P < 0.0001]. In a multivariate analysis of 17 baseline variables, patients with a CHADS2 score of 0 were 33% less likely to be in sinus rhythm than those with a CHADS2 score ≥2 (OR 0.66, CI 0.47-0.94; P = 0.0225). In the secondary analysis, spontaneous restoration of sinus rhythm was also found to predict sinus rhythm at end of study (OR 8.62, CI 1.54-48.16; P = 0.0142).
Conclusion
In X-VeRT, early cardioversion and high CHADS2 scores predicted sinus rhythm at 6 weeks from cardioversion.

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

Europace: 12 Jun 2021; epub ahead of print
Cappato R, Ezekowitz MD, Hohnloser SH, Meng IL, Wosnitza M, Camm AJ
Europace: 12 Jun 2021; epub ahead of print | PMID: 34128075
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Impact:
Abstract

Variables affecting the quality of anticoagulation in atrial fibrillation patients newly initiating vitamin K antagonists: insights from the national and multicentre SULTAN registry.

Rivera-Caravaca JM, Badimón L, Ferreira-Gonzalez I, Gómez-Doblas JJ, ... Anguita M, Marín F
Aims
Vitamin K antagonists (VKAs) are effective drugs reducing the risk for stroke in atrial fibrillation (AF), but the benefits derived from such therapy depend on the international normalized ratio (INR) maintenance in a narrow therapeutic range. Here, we aimed to determine independent variables driving poor anticoagulation control [defined as a time in therapeutic range (TTR) <65%] in a \'real world\' national cohort of AF patients.
Methods and results
The SULTAN registry is a multicentre, prospective study, involving patients with non-valvular AF from 72 cardiology units expert in AF in Spain. At inclusion, all patients naïve for oral anticoagulation were started with VKAs for the first time. For the analysis, the first month of anticoagulation and those patients with <3 INR determinations were disregarded. Patients were followed up during 1 year. A total of 870 patients (53.9% male, the mean age of 73.6 ± 9.2 years, mean CHA2DS2-VASc and HAS-BLED of 3.3 ± 1.5 and 1.4 ± 0.9, respectively) were included in the full analysis set. In overall, 7889 INR determinations were available. At 1-year, the mean TTR was 63.1 ± 22.1% and 49.2% patients had a TTR < 65%. Multivariate Cox regression analysis showed that coronary artery disease [odds ratio (OR) 1.81, 95% confidence interval (CI) 1.14-2.87; P = 0.012] and amiodarone use (OR 1.54, 95% CI 1.01-2.34; P = 0.046) were independently associated with poor quality of anticoagulation (TTR <65%).
Conclusion
This study demonstrated that the quality of anticoagulation in AF patients newly starting VKAs is sub-optimal. Previous coronary artery disease and concomitant use of amiodarone were identified as independent variables affecting the poor quality of VKA therapy during the first year.

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

Europace: 10 Jun 2021; epub ahead of print
Rivera-Caravaca JM, Badimón L, Ferreira-Gonzalez I, Gómez-Doblas JJ, ... Anguita M, Marín F
Europace: 10 Jun 2021; epub ahead of print | PMID: 34115857
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Impact:
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: 06 Jun 2021; 23:821-827
Chieng D, Finch S, Sugumar H, Taylor AJ, ... Kalman JM, Kistler PM
Europace: 06 Jun 2021; 23:821-827 | PMID: 33236092
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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: 06 Jun 2021; 23:828-836
Ellermann C, Wolfes J, Eckardt L, Frommeyer G
Europace: 06 Jun 2021; 23:828-836 | PMID: 33200170
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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: 06 Jun 2021; 23:837-843
Escobar C, Camm AJ
Europace: 06 Jun 2021; 23:837-843 | PMID: 33221894
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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.

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Europace: 06 Jun 2021; 23:918-927
Sieliwonczyk E, Alaerts M, Robyns T, Schepers D, ... Saenen J, Loeys B
Europace: 06 Jun 2021; 23:918-927 | PMID: 33221854
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Impact:
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: 06 Jun 2021; 23:907-917
Bariani R, Cipriani A, Rizzo S, Celeghin R, ... Perazzolo Marra M, Bauce B
Europace: 06 Jun 2021; 23:907-917 | PMID: 33313835
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Impact:
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, ... Dionisi Vici C, 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: 06 Jun 2021; 23:948-957
Di Mambro C, Tamborrino PP, Silvetti MS, Yammine ML, ... Dionisi Vici C, Drago F
Europace: 06 Jun 2021; 23:948-957 | PMID: 33336258
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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: 06 Jun 2021; 23:861-867
Lycke M, Kyriakopoulou M, El Haddad M, Wielandts JY, ... Duytschaever M, Knecht S
Europace: 06 Jun 2021; 23:861-867 | PMID: 33367708
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Impact:
Abstract

Safety, effectiveness, and quality of life following pulmonary vein isolation with a multi-electrode radiofrequency balloon catheter in paroxysmal atrial fibrillation: 1-year outcomes from SHINE.

Schilling R, Dhillon GS, Tondo C, Riva S, ... Gupta D, Reddy VY
Aims
To evaluate the safety and effectiveness of a compliant multi-electrode radiofrequency balloon catheter (RFB) used with a multi-electrode diagnostic catheter for pulmonary vein isolation (PVI).
Methods and results
This prospective, multicentre, single-arm study was conducted at six European sites and enrolled patients with symptomatic paroxysmal atrial fibrillation. The primary effectiveness endpoint was entrance block in treated pulmonary veins (PVs) after adenosine/isoproterenol challenge. The primary safety endpoint was the occurrence of primary adverse events (PAEs) within 7 days. Cerebral magnetic resonance imaging and neurological assessments were performed pre- and post-ablation in a subset of patients. Atrial arrhythmia recurrence was assessed over 12 months via transtelephonic and Holter monitoring. Quality of life was assessed by the Atrial Fibrillation Effect on Quality of Life (AFEQT) questionnaire. Of 85 patients undergoing ablation per study protocol, PV entrance block was achieved in all (one PV required touch-up with a focal catheter). Acute reconnection of ≥1 PVs after adenosine/isoproterenol challenge was observed in 9.3% (30/324) of PVs ablated. Post-ablation, silent cerebral lesions were detected in 9.7% (3/31) of patients assessed, all of which was resolved at 1-month follow-up. One patient experienced a PAE (retroperitoneal bleed). Freedom from documented symptomatic and all arrhythmia was 72.2% and 65.8% at 12 months. Four patients (4.7%) underwent repeat ablation. Significant improvements in all AFEQT subscale scores were seen at 6 and 12 months.
Conclusion
PVI with the novel RFB demonstrated favourable safety and effectiveness, with low repeat ablation rate and clinically meaningful improvement in quality of life.
Clinicaltrials.gov registration number
NCT03437733.

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

Europace: 06 Jun 2021; 23:851-860
Schilling R, Dhillon GS, Tondo C, Riva S, ... Gupta D, Reddy VY
Europace: 06 Jun 2021; 23:851-860 | PMID: 33450010
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Impact:
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: 06 Jun 2021; 23:970-977
Lu YY, Huang SY, Lin YK, Chen YC, ... Chen SA, Chen YJ
Europace: 06 Jun 2021; 23:970-977 | 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: 06 Jun 2021; 23:958-969
Obergassel J, O'Reilly M, Sommerfeld LC, Kabir SN, ... Kirchhof P, Fabritz L
Europace: 06 Jun 2021; 23:958-969 | PMID: 33462602
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Impact:
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: 06 Jun 2021; 23:868-877
Bordignon S, Chen S, Bologna F, Thohoku S, ... Schmidt B, Chun JKR
Europace: 06 Jun 2021; 23:868-877 | PMID: 33458770
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Abstract

Witnessed and unwitnessed sudden cardiac death: a nationwide study of persons aged 1-35 years.

Svane J, Lynge TH, Hansen CJ, Risgaard B, Winkel BG, Tfelt-Hansen J
Aims
The aim of this study is to compare clinical characteristics and causes of death among witnessed and unwitnessed sudden cardiac death (SCD) cases aged 1-35 years.
Methods and results
In this retrospective nationwide study, all deaths in persons aged 1-35 years in Denmark during 2000-09 were included (23.7 million person-years). Using the in-depth descriptive Danish death certificates and Danish nationwide registries, 860 cases of sudden, unexpected death were identified. Through review of autopsy reports and register data, we identified 635 cases of SCD of which 266 (42%) were witnessed and 326 (51%) were unwitnessed. In 43 cases (7%), witnessed status was missing. Clinical characteristics were overall similar between the two groups. We found a male predominance among unwitnessed SCD compared to witnessed SCD (71% and 62%, respectively, P-value 0.012), as well as more psychiatric comorbidity (20% and 13%, respectively, P-value 0.029). Unwitnessed SCD more often occurred during sleep whereas witnessed SCD more often occurred while the individual was awake and relaxed (P-value < 0.001). The autopsy rate among all SCD cases was 70% with no significant difference in autopsy rate between the two groups. Sudden unexplained death, which was the leading autopsy conclusion in both groups, was more frequent among unwitnessed SCD (P-value 0.001).
Conclusion
Several clinical characteristics and autopsy findings were similar between witnessed and unwitnessed SCD cases. Our data support the inclusion of both witnessed and unwitnessed cases in epidemiological studies of SCD cases aged 1-35 years, although the risk of misclassification is higher among unwitnessed and non-autopsied cases of SCD.

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

Europace: 06 Jun 2021; 23:898-906
Svane J, Lynge TH, Hansen CJ, Risgaard B, Winkel BG, Tfelt-Hansen J
Europace: 06 Jun 2021; 23:898-906 | PMID: 33595080
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Impact:
Abstract

Development and external validation of prediction models to predict implantable cardioverter-defibrillator efficacy in primary prevention of sudden cardiac death.

Verstraelen TE, van Barreveld M, van Dessel PHFM, Boersma LVA, ... Zwinderman AH, Wilde AAM
Aims
This study was performed to develop and externally validate prediction models for appropriate implantable cardioverter-defibrillator (ICD) shock and mortality to identify subgroups with insufficient benefit from ICD implantation.
Methods and results
We recruited patients scheduled for primary prevention ICD implantation and reduced left ventricular function. Bootstrapping-based Cox proportional hazards and Fine and Gray competing risk models with likely candidate predictors were developed for all-cause mortality and appropriate ICD shock, respectively. Between 2014 and 2018, we included 1441 consecutive patients in the development and 1450 patients in the validation cohort. During a median follow-up of 2.4 (IQR 2.1-2.8) years, 109 (7.6%) patients received appropriate ICD shock and 193 (13.4%) died in the development cohort. During a median follow-up of 2.7 (IQR 2.0-3.4) years, 105 (7.2%) received appropriate ICD shock and 223 (15.4%) died in the validation cohort. Selected predictors of appropriate ICD shock were gender, NSVT, ACE/ARB use, atrial fibrillation history, Aldosterone-antagonist use, Digoxin use, eGFR, (N)OAC use, and peripheral vascular disease. Selected predictors of all-cause mortality were age, diuretic use, sodium, NT-pro-BNP, and ACE/ARB use. C-statistic was 0.61 and 0.60 at respectively internal and external validation for appropriate ICD shock and 0.74 at both internal and external validation for mortality.
Conclusion
Although this cohort study was specifically designed to develop prediction models, risk stratification still remains challenging and no large group with insufficient benefit of ICD implantation was found. However, the prediction models have some clinical utility as we present several scenarios where ICD implantation might be postponed.

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

Europace: 06 Jun 2021; 23:887-897
Verstraelen TE, van Barreveld M, van Dessel PHFM, Boersma LVA, ... Zwinderman AH, Wilde AAM
Europace: 06 Jun 2021; 23:887-897 | PMID: 33582797
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Abstract

Enrichment of loss-of-function and copy number variants in ventricular cardiomyopathy genes in \'lone\' atrial fibrillation.

Lazarte J, Laksman ZW, Wang J, Robinson JF, ... Hegele RA, Roberts JD
Aims
Atrial fibrillation (AF) is a complex heritable disease whose genetic underpinnings remain largely unexplained, though recent work has suggested that the arrhythmia may develop secondary to an underlying atrial cardiomyopathy. We sought to evaluate for enrichment of loss-of-function (LOF) and copy number variants (CNVs) in genes implicated in ventricular cardiomyopathy in \'lone\' AF.
Methods and results
Whole-exome sequencing was performed in 255 early onset \'lone\' AF cases, defined as arrhythmia onset prior to 60 years of age in the absence of known clinical risk factors. Subsequent evaluations were restricted to 195 cases of European genetic ancestry, as defined by principal component analysis, and focused on a pre-defined set of 43 genes previously implicated in ventricular cardiomyopathy. Bioinformatic analysis identified 6 LOF variants (3.1%), including 3 within the TTN gene, among cases in comparison with 4 of 503 (0.80%) controls [odds ratio: 3.96; 95% confidence interval (CI): 1.11-14.2; P = 0.033]. Further, two AF cases possessed a novel heterozygous 8521 base pair TTN deletion, confirmed with Sanger sequencing and breakpoint validation, which was absent from 4958 controls (P = 0.0014). Subsequent cascade screening in two families revealed evidence of co-segregation of a LOF variant with \'lone\' AF.
Conclusion
\'Lone\' AF cases are enriched in rare LOF variants from cardiomyopathy genes, findings primarily driven by TTN, and a novel TTN deletion, providing additional evidence to implicate atrial cardiomyopathy as an AF genetic sub-phenotype. Our results also highlight that AF may develop in the context of these variants in the absence of a discernable ventricular cardiomyopathy.

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

Europace: 06 Jun 2021; 23:844-850
Lazarte J, Laksman ZW, Wang J, Robinson JF, ... Hegele RA, Roberts JD
Europace: 06 Jun 2021; 23:844-850 | PMID: 33682005
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Impact:
Abstract

Procedural efficiencies, lesion metrics, and 12-month clinical outcomes for Ablation Index-guided 50 W ablation for atrial fibrillation.

O\'Brien J, Obeidat M, Kozhuharov N, Ding WY, ... Snowdon RL, Gupta D
Aims
The safety of Ablation Index (AI)-guided 50 W ablation for atrial fibrillation (AF) remains uncertain, and mid-term clinical outcomes have not been described. The interplay between AI and its components at 50 W has not been reported.
Methods and results
Eighty-eight consecutive AF patients (44% paroxysmal) underwent AI-guided 50 W ablation. Procedural and 12-month clinical outcomes were compared with 93 consecutive controls (65% paroxysmal) who underwent AI-guided ablation using 35-40 W. Posterior wall isolation (PWI) was performed in 44 (50%) and 23 (25%) patients in the 50 and 35-40 W groups, respectively, P < 0.001. The last 10 patients from each group underwent analysis of individual lesions (n = 1230) to explore relationships between different powers and the AI components. Pulmonary vein isolation was successful in all patients. Posterior wall isolation was successful in 41/44 (93.2%) and 22/23 (95.7%) in the 50 and 35-40 W groups, respectively (P = 0.685). Radiofrequency times (20 vs. 26 min, P < 0.001) and total procedure times (130 vs. 156 min, P = 0.002) were significantly lower in the 50 W group. No complication or steam pop was seen in either group. Twelve-month freedom from arrhythmia was similar (80.2% vs. 82.8%, P = 0.918). A higher proportion of lesions in the 50 W group were associated with impedance drop >7 Ω (54.6% vs. 45.5%, P < 0.001). Excessive ablation (AI >600 anteriorly, >500 posteriorly) was more frequent in the 50 W group (9.7% vs. 4.3%, P < 0.001).
Conclusion
Ablation Index-guided 50 W AF ablation is as safe and effective as lower powers and results in reduced ablation and procedure times. Radiofrequency lesions are more likely to be therapeutic, but there is a higher risk of delivering excessive ablation.

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

Europace: 06 Jun 2021; 23:878-886
O'Brien J, Obeidat M, Kozhuharov N, Ding WY, ... Snowdon RL, Gupta D
Europace: 06 Jun 2021; 23:878-886 | PMID: 33693677
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Abstract

Persistence and adherence to non-vitamin K antagonist oral anticoagulant treatment in patients with atrial fibrillation across five Western European countries.

Komen JJ, Pottegård A, Mantel-Teeuwisse AK, Forslund T, ... Kjerpeseth LJ, Klungel OH
Aims
To assess persistence and adherence to non-vitamin K antagonist oral anticoagulant (NOAC) treatment in patients with atrial fibrillation (AF) in five Western European healthcare settings.
Methods and results
We conducted a multi-country observational cohort study, including 559 445 AF patients initiating NOAC therapy from Stockholm (Sweden), Denmark, Scotland, Norway, and Germany between 2011 and 2018. Patients were followed from their first prescription until they switched to a vitamin K antagonist, emigrated, died, or the end of follow-up. We measured persistence and adherence over time and defined adequate adherence as medication possession rate ≥90% among persistent patients only.
Results
Overall, persistence declined to 82% after 1 year and to 63% after 5 years. When including restarters of NOAC treatment, 85% of the patients were treated with NOACs after 5 years. The proportion of patients with adequate adherence remained above 80% throughout follow-up. Persistence and adherence were similar between countries and was higher in patients starting treatment in later years. Both first year persistence and adherence were lower with dabigatran (persistence: 77%, adherence: 65%) compared with apixaban (86% and 75%) and rivaroxaban (83% and 75%) and were statistically lower after adjusting for patient characteristics. Adherence and persistence with dabigatran remained lower throughout follow-up.
Conclusion
Persistence and adherence were high among NOAC users in five Western European healthcare settings and increased in later years. Dabigatran use was associated with slightly lower persistence and adherence compared with apixaban and rivaroxaban.

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

Europace: 06 Jun 2021; epub ahead of print
Komen JJ, Pottegård A, Mantel-Teeuwisse AK, Forslund T, ... Kjerpeseth LJ, Klungel OH
Europace: 06 Jun 2021; epub ahead of print | PMID: 34096584
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Abstract

Effective termination of atrial fibrillation by SK channel inhibition is associated with a sudden organization of fibrillatory conduction.

Gatta G, Sobota V, Citerni C, Diness JG, ... Schotten U, van Hunnik A
Aims
Pharmacological termination of atrial fibrillation (AF) remains a challenge due to limited efficacy and potential ventricular proarrhythmic effects of antiarrhythmic drugs. SK channels are proposed as atrial-specific targets in the treatment of AF. Here, we investigated the effects of the new SK channel inhibitor AP14145.
Methods and results
Eight goats were implanted with pericardial electrodes for induction of AF (30 days). In an open-chest study, the atrial conduction velocity (CV) and effective refractory period (ERP) were measured during pacing. High-density mapping of both atrial free-walls was performed during AF and conduction properties were assessed. All measurements were performed at baseline and during AP14145 infusion [10 mg/kg/h (n = 1) or 20 mg/kg/h (n = 6)]. At an infusion rate of 20 mg/kg/h, AF terminated in five of six goats. AP14145 profoundly increased ERP and reduced CV during pacing. AP14145 increased spatiotemporal instability of conduction at short pacing cycle lengths. Atrial fibrillation cycle length and pathlength (AF cycle length × CV) underwent a strong dose-dependent prolongation. Conduction velocity during AF remained unchanged and conduction patterns remained complex until the last seconds before AF termination, during which a sudden and profound organization of fibrillatory conduction occurred.
Conclusion
AP14145 provided a successful therapy for termination of persistent AF in goats. During AF, AP14145 caused an ERP and AF cycle length prolongation. AP14145 slowed CV during fast pacing but did not lead to a further decrease during AF. Termination of AF was preceded by an abrupt organization of AF with a decline in the number of fibrillation waves.

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

Europace: 02 Jun 2021; epub ahead of print
Gatta G, Sobota V, Citerni C, Diness JG, ... Schotten U, van Hunnik A
Europace: 02 Jun 2021; epub ahead of print | PMID: 34080619
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Abstract

Atrial fibrillation burden during the coronavirus disease 2019 pandemic.

O\'Shea CJ, Middeldorp ME, Thomas G, Harper C, ... Lau DH, Sanders P
Aims
The aim of this study is to determine the association between the coronavirus disease 2019 (COVID-19) pandemic and atrial fibrillation (AF) occurrence in individuals with cardiac implantable electronic devices (CIEDs).
Method and results
Multi-centre, observational, cohort study over a 100-day period during the COVID-19 pandemic (COVID-19) in the USA. Remote monitoring was used to assess AF episodes in patients with a CIED (pacemaker or defibrillator; 20 centres, 13 states). For comparison, the identical 100-day period in 2019 was used (Control). The primary outcomes were the AF burden during the COVID-19 pandemic, and the association of the pandemic with AF occurrence, as compared with 1 year prior. The secondary outcome was the association of AF occurrence with per-state COVID-19 prevalence. During COVID-19, 10 346 CIEDs with an atrial lead were monitored. There were 16 570 AF episodes of ≥6 min transmitted (16 events per 1000 patient days) with a significant increase in proportion of patients with AF episodes in high COVID-19 prevalence states compared with low prevalence states [odds ratio 1.34, 95% confidence interval (CI) 1.21-1.48, P < 0.001]. There were significantly more AF episodes during COVID-19 compared with Control [incident rate ratio (IRR) 1.33, 95% CI 1.25-1.40, P < 0.001]. This relationship persisted for AF episodes ≥1 h (IRR 1.65, 95% CI 1.53-1.79, P < 0.001) and ≥6 h (IRR 1.54, 95% CI 1.38-1.73, P < 0.001).
Conclusion
During the first 100 days of COVID-19, a 33% increase in AF episodes occurred with a 34% increase in the proportion of patients with AF episodes observed in states with higher COVID-19 prevalence. These findings suggest a possible association between pandemic-associated social disruptions and AF in patients with CIEDs.
Clinical trial registration
Australian New Zealand Clinical Trial Registry: ACTRN12620000692932.

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

Europace: 01 Jun 2021; epub ahead of print
O'Shea CJ, Middeldorp ME, Thomas G, Harper C, ... Lau DH, Sanders P
Europace: 01 Jun 2021; epub ahead of print | PMID: 34077513
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Abstract

Autonomic modulation and cardiac arrhythmias: old insights and novel strategies.

Chatterjee NA, Singh JP
The autonomic nervous system (ANS) plays a critical role in both health and states of cardiovascular disease. There has been a long-recognized role of the ANS in the pathogenesis of both atrial and ventricular arrhythmias (VAs). This historical understanding has been expanded in the context of evolving insights into the anatomy and physiology of the ANS, including dysfunction of the ANS in cardiovascular disease such as heart failure and myocardial infarction. An expanding armamentarium of therapeutic strategies-both invasive and non-invasive-have brought the potential of ANS modulation to contemporary clinical practice. Here, we summarize the integrative neuro-cardiac anatomy underlying the ANS, review the physiological rationale for autonomic modulation in atrial and VAs, highlight strategies for autonomic modulation, and finally frame future challenges and opportunities for ANS therapeutics.

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

Europace: 28 May 2021; epub ahead of print
Chatterjee NA, Singh JP
Europace: 28 May 2021; epub ahead of print | PMID: 34050642
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Impact:
Abstract

Optimized implementation of cardiac resynchronization therapy: a call for action for referral and optimization of care.

Mullens W, Auricchio A, Martens P, Witte K, ... Ruschitzka F, Leclercq C
Cardiac resynchronization therapy (CRT) is one of the most effective therapies for heart failure with reduced ejection fraction and leads to improved quality of life, reductions in heart failure hospitalization rates and all-cause mortality. Nevertheless, up to two-thirds of eligible patients are not referred for CRT. Furthermore, post-implantation follow-up is often fragmented and suboptimal, hampering the potential maximal treatment effect. This joint position statement from three European Society of Cardiology Associations, Heart Failure Association (HFA), European Heart Rhythm Association (EHRA) and European Association of Cardiovascular Imaging (EACVI), focuses on optimized implementation of CRT. We offer theoretical and practical strategies to achieve more comprehensive CRT referral and post-procedural care by focusing on four actionable domains: (i) overcoming CRT under-utilization, (ii) better understanding of pre-implant characteristics, (iii) abandoning the term \'non-response\' and replacing this by the concept of disease modification, and (iv) implementing a dedicated post-implant CRT care pathway.

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

Europace: 24 May 2021; epub ahead of print
Mullens W, Auricchio A, Martens P, Witte K, ... Ruschitzka F, Leclercq C
Europace: 24 May 2021; epub ahead of print | PMID: 34037728
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Abstract

Prevention of cardiac implantable electronic device infections: guidelines and conventional prophylaxis.

Blomstrom-Lundqvist C, Ostrowska B
Cardiac implantable electronic devices (CIED) are potentially life-saving treatments for several cardiac conditions, but are not without risk. Despite dissemination of recommended strategies for prevention of device infections, such as administration of antibiotics before implantation, infection rates continue to rise resulting in escalating health care costs. New trials conveying important steps for better prevention of device infection and an EHRA consensus paper were recently published. This document will review the role of various preventive measures for CIED infection, emphasizing the importance of adhering to published recommendations. The document aims to provide guidance on how to prevent CIED infections in clinical practice by considering modifiable and non-modifiable risk factors that may be present pre-, peri-, and/or post-procedure.

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

Europace: 24 May 2021; epub ahead of print
Blomstrom-Lundqvist C, Ostrowska B
Europace: 24 May 2021; epub ahead of print | PMID: 34037227
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Abstract

Long-term survival following upgrade compared with de novo cardiac resynchronization therapy implantation: a single-centre, high-volume experience.

Schwertner WR, Behon A, Merkel ED, Tokodi M, ... Kosztin A, Merkely B
Aims
Patients with a pacemaker or implantable cardioverter-defibrillator are often considered for cardiac resynchronization therapy (CRT). However, limited comprehensive data are available regarding their long-term outcomes.
Methods and results
Our retrospective registry included 2524 patients [1977 (78%) de novo, 547 (22%) upgrade patients] with mild to severe symptoms, left ventricular ejection fraction ≤35%, and QRS ≥ 130ms. The primary outcome was the composite of all-cause mortality, heart transplantation (HTX), or left ventricular assist device (LVAD) implantation; secondary endpoints were death from any cause and post-procedural complications. In our cohort, upgrade patients were older [71 (65-77) vs. 67 (59-73) years; P < 0.001], were less frequently females (20% vs. 27%; P = 0.002) and had more comorbidities than de novo patients. During the median follow-up time of 3.7 years, 1091 (55%) de novo and 342 (63%) upgrade patients reached the primary endpoint. In univariable analysis, upgrade patients exhibited a higher risk of mortality/HTX/LVAD than the de novo group [hazard ratio (HR): 1.41; 95% confidence interval (CI): 1.23-1.61; P < 0.001]. However, this difference disappeared after adjusting for covariates (adjusted HR: 1.12; 95% CI: 0.86-1.48; P = 0.402), or propensity score matching (propensity score-matched HR: 1.10; 95% CI: 0.95-1.29; P = 0.215). From device-related complications, lead dysfunction (3.1% vs. 1%; P < 0.001) and pocket infections (3.7% vs. 1.8%; P = 0.014) were more frequent in the upgrade group compared to de novo patients.
Conclusion
In our retrospective analysis, upgrade patients had a higher risk of all-cause mortality than de novo patients, which might be attributable to their more significant comorbidity burden. The occurrence of lead dysfunction and pocket infections was more frequent in the upgrade group.

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

Europace: 24 May 2021; epub ahead of print
Schwertner WR, Behon A, Merkel ED, Tokodi M, ... Kosztin A, Merkely B
Europace: 24 May 2021; epub ahead of print | PMID: 34037220
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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.

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Europace: 20 May 2021; 23:653-664
Ben-Haim Y, Asimaki A, Behr ER
Europace: 20 May 2021; 23:653-664 | PMID: 33200179
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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 May 2021; 23:797-805
de Jong JSY, Blok MRS, Thijs RD, Harms MPM, ... van Dijk N, de Lange FJ
Europace: 20 May 2021; 23:797-805 | PMID: 33219671
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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: 20 May 2021; 23:757-766
Beer D, Subzposh FA, Colburn S, Naperkowski A, Vijayaraman P
Europace: 20 May 2021; 23:757-766 | PMID: 33236070
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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: 20 May 2021; 23:789-796
Steger A, Dommasch M, Müller A, Sinnecker D, ... Malik M, Schmidt G
Europace: 20 May 2021; 23:789-796 | PMID: 33276379
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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: 20 May 2021; 23:740-747
Carabelli A, Jabeur M, Jacon P, Rinaldi CA, ... Neuzil P, Defaye P
Europace: 20 May 2021; 23:740-747 | PMID: 33313789
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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: 20 May 2021; 23:682-690
López-Canoa JN, Couselo-Seijas M, Baluja A, González-Melchor L, ... Eiras S, Rodríguez-Mañero M
Europace: 20 May 2021; 23:682-690 | PMID: 33319222
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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: 20 May 2021; 23:775-780
Steinfurt J, Bezzina CR, Biermann J, Staudacher D, ... Odening KE, Lodder EM
Europace: 20 May 2021; 23:775-780 | PMID: 33324992
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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: 20 May 2021; 23:665-673
Tiver KD, Quah J, Lahiri A, Ganesan AN, McGavigan AD
Europace: 20 May 2021; 23:665-673 | 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: 20 May 2021; 23:722-730
Tilz RR, Lenz C, Sommer P, Roza MS, ... Vogler J, Eitel C
Europace: 20 May 2021; 23:722-730 | PMID: 33351076
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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, CAPA Study Investigators
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.

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

Europace: 20 May 2021; 23:731-739
Wu G, Huang H, Cai L, Yang Y, ... Huang C, CAPA Study Investigators
Europace: 20 May 2021; 23:731-739 | PMID: 33367669
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Impact:
Abstract

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

Nair GM, Birnie DH, Sumner GL, Krahn AD, ... Essebag V, BRUISE CONTROL Investigators
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: 20 May 2021; 23:748-756
Nair GM, Birnie DH, Sumner GL, Krahn AD, ... Essebag V, BRUISE CONTROL Investigators
Europace: 20 May 2021; 23:748-756 | PMID: 33367623
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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: 20 May 2021; 23:781-788
Webster G, Aburawi EH, Chaix MA, Chandler S, ... Wilde AAM, Bhuiyan ZA
Europace: 20 May 2021; 23:781-788 | PMID: 33367594
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Impact:
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: 20 May 2021; 23:691-700
Nalliah CJ, Wong GR, Lee G, Voskoboinik A, ... Sanders P, Kalman JM
Europace: 20 May 2021; 23:691-700 | PMID: 33447844
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Impact:
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: 20 May 2021; 23:674-681
Börschel CS, Ohlrogge AH, Geelhoed B, Niiranen T, ... Salomaa V, Schnabel RB
Europace: 20 May 2021; 23:674-681 | PMID: 33458771
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Impact:
Abstract

High-power short duration vs. conventional radiofrequency ablation of atrial fibrillation: a systematic review and meta-analysis.

Ravi V, Poudyal A, Abid QU, Larsen T, ... Trohman RG, Huang HD
Aims
We sought to compare the effectiveness and safety of high-power short-duration (HPSD) radiofrequency ablation (RFA) with conventional RFA in patients with atrial fibrillation (AF).
Methods and results
MEDLINE, Cochrane, and ClinicalTrials.gov databases were searched until 15 May 2020 for relevant studies comparing HPSD vs. conventional RFA in patients undergoing initial catheter ablation for AF. A total of 15 studies involving 3718 adult patients were included in our meta-analysis (2357 in HPSD RFA and 1361 in conventional RFA). Freedom from atrial arrhythmia was higher in HPSD RFA when compared with conventional RFA [odds ratio (OR) 1.44, 95% confidence interval (CI) 1.10-1.90; P = 0.009]. Acute PV reconnection was lower (OR 0.56, P = 0.005) and first-pass isolation was higher (OR 3.58, P < 0.001) with HPSD RFA. There was no difference in total complications between the two groups (P = 0.19). Total procedure duration [mean difference (MD) -37.35 min, P < 0.001], fluoroscopy duration (MD -5.23 min, P = 0.001), and RF ablation time (MD -16.26 min, P < 0.001) were all significantly lower in HPSD RFA. High-power short-duration RFA also demonstrated higher freedom from atrial arrhythmia in the subgroup analysis of patients with paroxysmal AF (OR 1.80, 95% CI 1.29-2.50; P < 0.001), studies with ≥50 W protocol in the HPSD RFA group (OR 1.53, 95% CI 1.08-2.18; P = 0.02] and studies with contact force sensing catheter use (OR 1.65, 95% CI 1.21-2.25; P = 0.002).
Conclusion
High-power short-duration RFA was associated with better procedural effectiveness when compared with conventional RFA with comparable safety and shorter procedural duration.

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

Europace: 20 May 2021; 23:710-721
Ravi V, Poudyal A, Abid QU, Larsen T, ... Trohman RG, Huang HD
Europace: 20 May 2021; 23:710-721 | PMID: 33523184
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Impact:
Abstract

Extra-pulmonary vein driver mapping and ablation for persistent atrial fibrillation in obese patients.

Hu X, Jiang W, Wu S, Xu K, ... Liu X, Qin M
Aims
The aim of this study was to determine whether driver ablation effectively treats persistent atrial fibrillation (AF) in obese patients.
Methods and results
We randomly assigned 124 persistent AF obese patients to two groups, one undergoing conventional ablation (n = 62) and the other undergoing driver ablation (n = 62). Sixty-two non-obese patients with persistent AF undergoing driver ablation served as matched controls. Bipolar electrogram dispersion was analysed for driver mapping. Epicardial adipose tissue (EAT) volume was measured using cardiac computed tomography. Obese patients had a higher proportion of driver regions in the posterior wall (56.5% vs. 32.3%, P = 0.007). Driver complexity, measured as the average number and area of driver regions, was higher in the obese group than in the non-obese group (3.5 ± 1.0 vs. 2.9 ± 0.9, P < 0.001; 15.5% ± 4.2% vs. 9.8 ± 2.6%, P < 0.001, respectively). Left atrial EAT volume correlated better with the proportion of area of driver regions than did body mass index (BMI) and total EAT (BMI: r2 = 0.250, P < 0.001; total EAT: r2 = 0.379, P < 0.001; and left atrial EAT: r2 = 0.439, P < 0.001). The rate of AF termination was significantly higher in the driver ablation group than in the conventional ablation group (82.9% vs. 22.8%, P < 0.001). During the follow-up period of 16.9 ± 6.5 months, patients in the driver ablation group had significantly better AF-free survival (91.91% vs. 79.0%, log rank test, P = 0.026) and AF/atrial tachycardia-free survival (83.9% vs. 64.5%, log rank test, P = 0.011) than did patients in the conventional ablation group.
Conclusion
Obesity is associated with increased driver complexity. Driver ablation improves long-term outcomes in obese patients with persistent AF.

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

Europace: 20 May 2021; 23:701-709
Hu X, Jiang W, Wu S, Xu K, ... Liu X, Qin M
Europace: 20 May 2021; 23:701-709 | PMID: 33554255
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Impact:
Abstract

Economic evaluation of an absorbable antibiotic envelope for prevention of cardiac implantable electronic device infection.

Rennert-May E, Raj SR, Leal J, Exner DV, Manns BJ, Chew DS
Aims
Recent evidence suggests that an antibiotic impregnated envelope inserted at time of cardiac implantable electronic device (CIED) implantation may reduce risk of subsequent CIED infection compared with standard of care (SoC). The objective of the current work was to perform a cost-effectiveness analysis comparing an antibiotic impregnated envelope with SoC at time of CIED insertion.
Methods and results
Decision analytic models were used to project healthcare costs and benefits of two strategies, an antibiotic impregnated envelope plus SoC (Env+SoC) vs. SoC alone, in a cohort of patients undergoing CIED implantation over a 1-year time horizon. Evidence from published literature informed the model inputs. Probabilistic and deterministic sensitivity analyses were performed. The primary outcome was the incremental cost per infection prevented, assessed from the Canadian healthcare system perspective. Envelope plus SoC was associated with fewer CIED infection (7 CIED infections/1000 patients) at higher total costs ($29 033 000/1000 patients) compared with SoC (11 CIED infections and $27 926 000/1000 patients). The incremental cost per infection prevented over 1 year was $274 416. Use of Env+SoC was cost saving only when baseline CIED infection risk was increased to 6% (vs. base case of 1.2%).
Conclusions
A strategy of Env+SoC was not economically favourable compared with SoC alone, and the opportunity cost of widescale implementation should be considered. Future work is required to develop validated risk stratification tools to identify patients at greatest risk of CIED infection. The value proposition of Env+SoC improves when applying this intervention to patients at greatest infection risk.

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

Europace: 20 May 2021; 23:767-774
Rennert-May E, Raj SR, Leal J, Exner DV, Manns BJ, Chew DS
Europace: 20 May 2021; 23:767-774 | PMID: 33554239
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Impact:
Abstract

Antithrombotic therapy for stroke prevention in patients with atrial fibrillation who survive an intracerebral haemorrhage: results of an EHRA survey.

Ivany E, Lane DA, Dan GA, Doehner W, ... Lenarczyk R, Potpara TS
The aim of this survey is to provide a snapshot of current practice regarding antithrombotic therapy (ATT) in patients with atrial fibrillation (AF) comorbid with intracerebral haemorrhage (ICH). An online survey was distributed to members of the European Heart Rhythm Association. A total of 163 clinicians responded, mostly cardiologists or electrophysiologists (87.7%), predominantly working in University hospitals (61.3%). Most respondents (47.2%) had seen one to five patients with AF comorbid with ICH in the last 12 months. Among patients sustaining an ICH on oral anticoagulation (OAC), 84.3% respondents would consider some form of ATT post-ICH, with 73.2% preferring to switch from a vitamin-K antagonist (VKA) to a non-VKA oral anticoagulant (NOAC) and 37.2% preferring to switch from one NOAC to another. Most (36.6%) would restart OAC >30 days post-ICH. Among patients considered unable to take OAC, left atrial appendage occlusion procedure was the therapy of choice in 73.3% respondents. When deciding on ATT, respondents considered patient\'s CHA2DS2-VASc score, ICH type, demographics, risk factors, and patient adherence. The main reason for not restarting or commencing ATT was concern about recurrent ICH (80.8%). National or international clinical guidelines would be advantageous to support decision-making (84.3%). Other helpful resources reported were multidisciplinary team involvement (46.9%) and patient education (82%). In summary, most survey respondents would prescribe OAC therapy for patients with AF who have sustained an ICH on OAC and would restart OAC >30 days post-ICH. The risk of recurrent ICH was the main reason for not prescribing any ATT post-ICH.

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

Europace: 20 May 2021; 23:806-814
Ivany E, Lane DA, Dan GA, Doehner W, ... Lenarczyk R, Potpara TS
Europace: 20 May 2021; 23:806-814 | PMID: 34020460
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Impact:
Abstract

A randomized study of yoga therapy for the prevention of recurrent reflex vasovagal syncope.

Shenthar J, Gangwar RS, Banavalikar B, Benditt DG, Lakkireddy D, Padmanabhan D
Aims
Vasovagal syncope (VVS) is a common cardiovascular dysautonomic disorder that significantly impacts health and quality of life (QoL). Yoga has been shown to have a positive influence on cardiovascular autonomics. This study assessed the effectiveness of yoga therapy on the recurrence of VVS and QoL.
Methods and results
We randomized subjects with recurrent reflex VVS (>3 episodes in the past 1 year) and positive head-up tilt test to guideline-directed therapy (Group 1) or yoga therapy (Group 2). Patients in Group 1 were advised guideline-directed treatment and Group 2 was taught yoga by a certified instructor. The primary endpoint was VVS recurrences and QoL. Between June 2015 and February 2017, 97 highly symptomatic VVS patients were randomized (Group 1: 47 and Group 2: 50). The mean age was 33.1 ± 16.6 years, male:female of 40:57, symptom duration of 17.1 ± 20.7 months, with a mean of 6.4 ± 6.1 syncope episodes. Over a follow-up of 14.3 ± 2.1 months Group 2 had significantly lower syncope burden compared with Group 1 at 3 (0.8 ± 0.9 vs. 1.8 ± 1.4, P < 0.001), 6 (1.0 ± 1.2 vs. 3.4 ± 3.0, P < 0.001), and at 12 months (1.1 ± 0.8 vs. 3.8 ± 3.2, P < 0.001). The Syncope functional score questionnaire was significantly lower in Group 2 compared with Group 1 at 3 (31.4 ± 7.2 vs. 64.1 ± 11.5, P < 0.001), 6 (26.4 ± 6.3 vs. 61.4 ± 10.7, P < 0.001), and 12 months (22.2 ± 4.7 vs. 68.3 ± 11.4, P < 0.001).
Conclusion
For patients with recurrent VVS, guided yoga therapy is superior to conventional therapy in reducing symptom burden and improving QoL.

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

Europace: 19 May 2021; epub ahead of print
Shenthar J, Gangwar RS, Banavalikar B, Benditt DG, Lakkireddy D, Padmanabhan D
Europace: 19 May 2021; epub ahead of print | PMID: 34015829
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Impact:
Abstract

Obstructive sleep apnoea testing and management in atrial fibrillation patients: a joint survey by the European Heart Rhythm Association (EHRA) and the Association of Cardiovascular Nurses and Allied Professions (ACNAP).

Desteghe L, Hendriks JML, Heidbuchel H, Potpara TS, Lee GA, Linz D
Obstructive sleep apnoea (OSA) is highly prevalent in atrial fibrillation (AF) patients and associated with reduced response to rhythm control strategies. However, there is no practical guidance on testing for OSA in AF patients and for OSA treatment implementation. We sought to evaluate current practices and identify challenges of OSA management in AF. A descriptive cross-sectional study was performed with a content-validated survey to evaluate OSA management in AF by healthcare practitioners. Survey review, editing, and dissemination occurred via the European Heart Rhythm Association and the Association of Cardiovascular Nursing and Allied Professions and direct contact with arrhythmia centres. In total, 186 responses were collected. OSA-related symptoms were ranked as the most important reason to test for OSA in AF patients. The majority (67.7%) indicated that cardiologists perform \'ad-hoc\' referrals. Only 11.3% initiated systematic testing by home sleep test or respiratory polygraphy and in addition, 10.8% had a structured OSA assessment pathway in place at the cardiology department. Only 6.7% of the respondents indicated that they test >70% of their AF patients for OSA as a component of rhythm control therapy. Various barriers were reported: no established collaboration between cardiology and sleep clinic (35.6%); lack in skills and knowledge (23.6%); lack of financial (23.6%) and personnel-related resources (21.3%). Structured testing for OSA occurs in the minority of AF patients. Centres apply varying methods. There is an urgent need for increased awareness and standardized pathways to allow OSA testing and treatment integration in the management of AF.

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

Europace: 16 May 2021; epub ahead of print
Desteghe L, Hendriks JML, Heidbuchel H, Potpara TS, Lee GA, Linz D
Europace: 16 May 2021; epub ahead of print | PMID: 34000040
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Impact:
Abstract

Role of pre-operative transthoracic echocardiography in predicting post-operative atrial fibrillation after cardiac surgery: a systematic review of the literature and meta-analysis.

Kawczynski MJ, Gilbers M, Van De Walle S, Schalla S, ... Maesen B, Bidar E
Aims
This systematic review and meta-analysis aims to evaluate the role of pre-operative transthoracic echocardiography in predicting post-operative atrial fibrillation (POAF) after cardiac surgery.
Methods and results
Electronic databases were searched for studies reporting on pre-operative echocardiographic predictors of POAF in PubMed, Cochrane library, and Embase. A meta-analysis of echocardiographic predictors of POAF that were identified by at least five different publications was performed. Forty-three publications were included in this systematic review. Echocardiographic predictors for POAF included surrogate parameters for total atrial conduction time (TACT), structural cardiac changes, and functional disturbances. Meta-analysis showed that prolonged pre-operative PA-TDI interval [5 studies, Cohen\'s d = 1.4, 95% confidence interval (CI) 0.9-1.9], increased left atrial volume indexed for body surface area (LAVI) (23 studies, Cohen\'s d = 0.8, 95% CI 0.6-1.0), and reduced peak atrial longitudinal strain (PALS) (5 studies, Cohen\'s d = 1.4, 95% CI 1.0-1.8), were associated with POAF incidence. Left atrial volume indexed for body surface was the most important predicting factor in patients without a history of AF. These parameters remained important predictors of POAF in heterogeneous populations with variable age and comorbidities such as coronary artery disease and valvular disease.
Conclusion
This meta-analysis shows that increased TACT, increased LAVI, and reduced PALS are valuable parameters for predicting POAF in the early post-operative phase in a large variety of patients.

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

Europace: 16 May 2021; epub ahead of print
Kawczynski MJ, Gilbers M, Van De Walle S, Schalla S, ... Maesen B, Bidar E
Europace: 16 May 2021; epub ahead of print | PMID: 34000038
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Impact:
Abstract

Real-time intracardiac echocardiography validation of saline-enhanced radiofrequency needle-tip ablation: lesion characteristics and gross pathology correlation.

Dickow J, Wang S, Suzuki A, Imamura K, ... Curley MG, Packer DL
Aims
With the implementation of saline-enhanced radiofrequency (SERF) needle-tip ablation, real-time validation of lesion formation is needed for the controllable creation of transmural lesions. The aim of the study was to analyse the ability of two-dimensional intracardiac echocardiography (2D-ICE) to guide and validate SERF ablation in real-time.
Methods and results
Fifty-six SERF energy deliveries at left ventricular sites of 11 dogs guided by 2D-ICE were analysed (power: 15-50 W; time: 25-120 s; irrigation saline: 60°C with 10 mL/min flow rate). Catheter tip/tissue orientation and lesion formation could be well detected by 2D-ICE in 49 (87.5%) energy deliveries. Gross pathology analysis confirmed excellent 2D-ICE lesion localization, the ability to detect transmural lesions (70% sensitivity, 47% specificity) and positive correlation between 2D-ICE and the corresponding gross pathology measurements of \'maximal lesion depth\'; (repeated measures correlation: rrm = 0.43, P = 0.012) and \'depth at maximal lesion width\' ([email protected]; rrm = 0.51, P = 0.003). The median angle between SERF catheter tip and endocardium was 76° [interquartile range (IQR) 58-83°]. The more perpendicular the catheter tip/tissue orientation was the deeper [email protected] (rrm = 0.32, P = 0.045). Grade 3 microbubbles on 2D-ICE during ablation, indicating inadequate catheter tip/tissue contact, was associated with smaller lesion volumes than with Grade 1 microbubbles (284.8 mm3 [IQR 151.3-343.1] vs. 2114.1 mm3 [IQR 1437.0-3026.3], P < 0.001).
Conclusion
With excellent lesion localization and a 70% detection rate of transmural lesions, 2D-ICE is well suited to validate SERF ablation lesion formation in real-time. The catheter tip/tissue angle impacts the lesion formation and through perpendicular catheter positioning, deeper intramural areas of the myocardium can be reached.

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

Europace: 15 May 2021; epub ahead of print
Dickow J, Wang S, Suzuki A, Imamura K, ... Curley MG, Packer DL
Europace: 15 May 2021; epub ahead of print | PMID: 33993234
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Impact:
Abstract

Antithrombotic treatment management in low stroke risk patients undergoing cardioversion of atrial fibrillation <48 h duration: results of an EHRA survey.

Migliore F, Providencia R, Farkowski MM, Dan GA, ... Zorzi A, Boveda S
Data supporting the safety of cardioversion (CV) of atrial fibrillation (AF) without anticoagulation in patients with AF duration <48 h are scarce. Observational studies suggest that the risk of stroke in these patients is very low when the definite duration of the AF episode is of <48 h and the clinical risk profile as estimated through the CHA2DS2VASc score is low (a score of 0 for men and 1 for women). As the recent 2020 European Society of Cardiology (ESC) guidelines indication for this clinical scenario is based mainly on consensus, we sent out a survey to assess the current clinical practice on anticoagulation prior to and post-CV in patients with AF <24-48 h duration and low stroke risk across centres in Europe. Of the 136 respondents, half were affiliated to university hospitals (68/136; 50%). Non-university hospitals (50/136; 36%) and private hospitals (2/136; 1.4%) accounted over a third of respondents. The main findings of our survey were (i) heterogeneity in the anticoagulation management both before and post-CV in low stroke-risk patients with AF <48 h, (ii) higher utilization of periprocedural low-molecular-weight heparin than of non-vitamin K antagonist oral anticoagulant, (iii) higher utilization of pre-CV transoesophageal echocardiography for electrical CV than for pharmacological CV regardless of the duration of AF, (iv) high adherence to a 4-week post-CV oral anticoagulant (OAC) therapy, mainly for electrical CV, and finally, (v) perceived higher acceptance of lack of post-CV OAC therapy in patients with <24 h than 24-48 h episode duration. The results obtained in this survey highlight the need for more research providing definitive clarification on the safety of CV without anticoagulation in patients with short duration AF.

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

Europace: 14 May 2021; epub ahead of print
Migliore F, Providencia R, Farkowski MM, Dan GA, ... Zorzi A, Boveda S
Europace: 14 May 2021; epub ahead of print | PMID: 33990842
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Impact:
Abstract

Impact of closed loop stimulation on prognostic cardiopulmonary variables in patients with chronic heart failure and severe chronotropic incompetence: a pilot, randomized, crossover study.

Proff J, Merkely B, Papp R, Lenz C, ... Landmesser U, Roser MJ
Aims
Clinical effects of rate-adaptive pacing in heart failure patients with chronotropic incompetence (CI) undergoing cardiac resynchronization therapy (CRT) remain unclear. Closed loop stimulation (CLS) is a new rate-adaptive sensor in CRT devices. We evaluated the effectiveness of CLS in CRT patients with severe CI, focusing primarily on key prognostic variables assessed by cardiopulmonary exercise (CPX) testing.
Methods and results
In the randomized, crossover, multicentre BIO|CREATE study, 20 CRT patients with severe CI and NYHA Class II/III (60%/40%) were randomized 1:1 to the sequence DDD-40 mode to DDD-CLS mode, or the sequence DDD-CLS mode to DDD-40 mode (1 month in each mode). Patients underwent symptom-limited treadmill-based CPX test in each mode. An improvement (decrease) of the ventilatory efficiency (VE) slope of ≥5% during CLS was regarded as positive response to CLS. Seventeen patients with full data sets had a mean intra-individual VE slope change of -1.8 ± 3.0 (-4.1%) with CLS (P = 0.23). Eight patients (47%) were CLS responders, with a -6.1 ± 2.7 (-16.4%) slope change (P = 0.029). Compared to non-responders, CLS responders had a higher left ventricular (LV) ejection fraction (46 ± 3 vs. 36 ± 9%; P = 0.0070), smaller end-diastolic LV volume (121 ± 34 vs. 181 ± 41 mL; P = 0.0085), smaller end-systolic LV volume (65 ± 23 vs. 114 ± 39 mL; P = 0.0076), and were predominantly in NYHA Class II (P = 0.0498).
Conclusion
The data of the present pilot study are compatible with the notion that CLS activation may improve VE slope in CRT patients with severe CI and less advanced heart failure. Further research is needed to determine the long-term clinical outcomes of CLS.

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

Europace: 12 May 2021; epub ahead of print
Proff J, Merkely B, Papp R, Lenz C, ... Landmesser U, Roser MJ
Europace: 12 May 2021; epub ahead of print | PMID: 33982093
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Impact:
Abstract

Proximity to the descending aorta predicts regional fibrosis in the adjacent left atrial wall: aetiopathogenic and prognostic implications.

Caixal G, Althoff T, Garre P, Alarcón F, ... Guasch E, Mont L
Aims
Left atrial (LA) fibrosis is present in patients with atrial fibrillation (AF) and can be visualized by magnetic resonance imaging with late gadolinium enhancement (LGE-MRI). Previous studies have shown that LA fibrosis is not randomly distributed, being more frequent in the area adjacent to the descending aorta (DAo). The objective of this study is to analyse the relationship between fibrosis in the atrial area adjacent to the DAo and the distance to it, as well as the prognostic implications of this fibrosis.
Methods and results
Magnetic resonance imaging with late gadolinium enhancement was obtained in 108 patients before AF ablation to analyse the extent of LA fibrosis and the distance DAo-to-LA. A high-density electroanatomic map was performed in a subgroup of 16 patients to exclude the possibility of an MRI artifact. Recurrences after ablation were analysed at 1 year of follow-up. The extent of atrial fibrosis in the area adjacent to the DAo was inversely correlated with the distance DAo-to-LA (r = -0.34, P < 0.001). This area had the greatest intensity of LGE [image intensity ratio (IIR) 1.14 ± 0.15 vs. 0.99 ± 0.16; P < 0.001] and also the lowest voltage (1.07 ± 0.86 vs. 1.54 ± 1.07 mV; P < 0.001) and conduction velocity (0.65 ± 0.06 vs. 0.96 ± 0.57 mm/ms; P < 0.001). The extent of this regional fibrosis predicted recurrence after AF ablation [hazard ratio (HR) 1.02, 95% CI 1.01-1.03; P = 0.01], however total fibrosis did not (HR = 1.01, 95% CI 0.97-1.06, P = 0.54).
Conclusions
Atrial fibrosis was predominantly located in the area adjacent to the DAo, and increased with the proximity between the two structures. Furthermore, this regional fibrosis better predicted recurrence after AF ablation than total atrial fibrosis.

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

Europace: 10 May 2021; epub ahead of print
Caixal G, Althoff T, Garre P, Alarcón F, ... Guasch E, Mont L
Europace: 10 May 2021; epub ahead of print | PMID: 33975341
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Impact:
Abstract

New safe approach to target symptomatic Hisian ectopy/tachycardia.

Chaumont C, Savouré A, Godin B, Mirolo A, Rivron S, Anselme F
Aims
Although cryoenergy safety profile is appropriate for the ablation of arrhythmogenic foci near the conduction system, mapping using the cryoablation catheter is of limited precision. Combining the safety of cryoenergy and the high precision of a 3D mapping system therefore appears the most appropriate set-up for ablation in the vicinity of the His bundle.
Methods and results
A 29-year-old woman with a 3-year history of increasing shortness of breath and palpitations refractory to medical treatment was sent to the electrophysiology (EP) laboratory for catheter ablation. Surface electrocardiogram showed sinus rhythm and frequent ectopic beats with narrow QRS complexes similar to those of the sinus beats. The left ventricular ejection fraction was impaired (38%) with no other aetiology found, apart from frequent ectopies. Detailed intracardiac mapping, using a 3D electroanatomical system, revealed that the ectopy originated from the distal His bundle, which was indicated by both antegrade and reversed His bundle activation sequence during ectopy compared to that during sinus rhythm. Due to the proximity of the conduction system, cryoenergy rather than radiofrequency was chosen to target this Hisian ectopy. A special set-up was made in order to allow the cryoablation catheter to be visualized into the 3D mapping system. Cryoenergy delivered to the site of earliest Hisian ectopy activation completely abolished it.
Conclusion
Such a combined approach may help to improve the therapeutic strategy for ablation procedures with a high risk of injury to the conduction system. It could notably be extended to the ablation of para-Hisian ectopy or accessory pathways.

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

Europace: 10 May 2021; epub ahead of print
Chaumont C, Savouré A, Godin B, Mirolo A, Rivron S, Anselme F
Europace: 10 May 2021; epub ahead of print | PMID: 33975338
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Abstract

Identification of local atrial conduction heterogeneities using high-density conduction velocity estimation.

van Schie MS, Heida A, Taverne YJHJ, Bogers AJJC, de Groot NMS
Aims
Accurate determination of intra-atrial conduction velocity (CV) is essential to identify arrhythmogenic areas. The most optimal, commonly used, estimation methodology to measure conduction heterogeneity, including finite differences (FiD), polynomial surface fitting (PSF), and a novel technique using discrete velocity vectors (DVV), has not been determined. We aim (i) to identify the most suitable methodology to unravel local areas of conduction heterogeneities using high-density CV estimation techniques, (ii) to quantify intra-atrial differences in CV, and (iii) to localize areas of CV slowing associated with paroxysmal atrial fibrillation (PAF).
Methods and results
Intra-operative epicardial mapping (>5000 sites, interelectrode distances 2 mm) of the right and left atrium and Bachmann\'s bundle (BB) was performed during sinus rhythm (SR) in 412 patients with or without PAF. The median atrial CV estimated using the DVV, PSF, and FiD techniques was 90.0 (62.4-116.8), 92.0 (70.6-123.2), and 89.4 (62.5-126.5) cm/s, respectively. The largest difference in CV estimates was found between PSF and DVV which was caused by smaller CV magnitudes detected only by the DVV technique. Using DVV, a lower CV at BB was found in PAF patients compared with those without atrial fibrillation (AF) [79.1 (72.2-91.2) vs. 88.3 (79.3-97.2) cm/s; P < 0.001].
Conclusions
Areas of local conduction heterogeneities were most accurately identified using the DVV technique, whereas PSF and FiD techniques smoothen wavefront propagation thereby masking local areas of conduction slowing. Comparing patients with and without AF, slower wavefront propagation during SR was found at BB in PAF patients, indicating structural remodelling.

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

Europace: 09 May 2021; epub ahead of print
van Schie MS, Heida A, Taverne YJHJ, Bogers AJJC, de Groot NMS
Europace: 09 May 2021; epub ahead of print | PMID: 33970234
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Abstract

Pulsed field ablation selectively spares the oesophagus during pulmonary vein isolation for atrial fibrillation.

Cochet H, Nakatani Y, Sridi-Cheniti S, Cheniti G, ... Haïssaguerre M, Jais P
Aims
Extra-atrial injury can cause complications after catheter ablation for atrial fibrillation (AF). Pulsed field ablation (PFA) has generated preclinical data suggesting that it selectively targets the myocardium. We sought to characterize extra-atrial injuries after pulmonary vein isolation (PVI) between PFA and thermal ablation methods.
Methods and results
Cardiac magnetic resonance (CMR) imaging was performed before, acutely (<3 h) and 3 months post-ablation in 41 paroxysmal AF patients undergoing PVI with PFA (N = 18, Farapulse) or thermal methods (N = 23, 16 radiofrequency, 7 cryoballoon). Oesophageal and aortic injuries were assessed by using late gadolinium-enhanced (LGE) imaging. Phrenic nerve injuries were assessed from diaphragmatic motion on intra-procedural fluoroscopy. Baseline CMR showed no abnormality on the oesophagus or aorta. During ablation procedures, no patient showed phrenic palsy. Acutely, thermal methods induced high rates of oesophageal lesions (43%), all observed in patients showing direct contact between the oesophagus and the ablation sites. In contrast, oesophageal lesions were observed in no patient ablated with PFA (0%, P < 0.001 vs. thermal methods), despite similar rates of direct contact between the oesophagus and the ablation sites (P = 0.41). Acute lesions were detected on CMR on the descending aorta in 10/23 (43%) after thermal ablation, and in 6/18 (33%) after PFA (P = 0.52). CMR at 3 months showed a complete resolution of oesophageal and aortic LGE in all patients. No patient showed clinical complications.
Conclusion
PFA does not induce any signs of oesophageal injury on CMR after PVI. Due to its tissue selectivity, PFA may improve safety for catheter ablation of AF.

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

Europace: 06 May 2021; epub ahead of print
Cochet H, Nakatani Y, Sridi-Cheniti S, Cheniti G, ... Haïssaguerre M, Jais P
Europace: 06 May 2021; epub ahead of print | PMID: 33961027
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