Topic: Electrophysiology

Abstract

Day-to-day measurement of physical activity and risk of atrial fibrillation.

Bonnesen MP, Frodi DM, Haugan KJ, Kronborg C, ... Svendsen JH, Diederichsen SZ
Aims 
The aim of this study was to investigate the association between within-individual changes in physical activity and onset of atrial fibrillation (AF).
Methods and results 
A total of 1410 participants from the general population (46.2% women, mean age 74.7 ± 4.1 years) with risk factors but with no prior AF diagnosis underwent continuous monitoring for AF episodes along with daily accelerometric assessment of physical activity using an implantable loop recorder during ≈3.5 years. The combined duration of monitoring was ≈1.6 million days, where 10 851 AF episodes lasting ≥60 min were detected in 361 participants (25.6%) with a median of 5 episodes (2, 25) each. The median daily physical activity was 112 (66, 168) min/day. A dynamic parameter describing within-individual changes in daily physical activity, i.e. average daily activity in the last week compared to the previous 100 days, was computed and used to model the onset of AF. A 1-h decrease in average daily physical activity was associated with AF onset the next day [odds ratio 1.24 (1.18-1.31)]. This effect was modified by overall level of activity (P < 0.001 for interaction), and the signal was strongest in the tertile of participants with lowest activity overall [low: 1.62 (1.41-1.86), mid: 1.27 (1.16-1.39), and high: 1.10 (1.01-1.19)].
Conclusions 
Within-individual changes in physical activity are associated with the onset of AF episodes as detected by continuous monitoring in a high-risk population. For each person, a 1-h decrease in daily physical activity during the last week increased the odds of AF onset the next day by ≈25%, while the strongest association was seen in the group with the lowest activity overall.
Clinical trial registration
ClinicalTrials.gov, identifier: NCT02036450.

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

Eur Heart J: 06 Oct 2021; 42:3979-3988
Bonnesen MP, Frodi DM, Haugan KJ, Kronborg C, ... Svendsen JH, Diederichsen SZ
Eur Heart J: 06 Oct 2021; 42:3979-3988 | PMID: 34471928
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Abstract

Epigenetic Age and the Risk of Incident Atrial Fibrillation.

Roberts JD, Vittinghoff E, Lu AT, Alonso A, ... Horvath S, Marcus GM
Background: The most prominent risk factor for atrial fibrillation (AF) is chronological age, however underlying mechanisms are unexplained. Algorithms using epigenetic modifications to the human genome effectively predict chronological age. Chronological and epigenetic predicted ages may diverge, a phenomenon termed epigenetic age acceleration (EAA), which may reflect accelerated biological aging. We sought to evaluate for associations between epigenetic age measures and incident AF.
Methods:
Measures for 4 epigenetic clocks (Horvath, Hannum, DNAm PhenoAge, and DNAm GrimAge) and an epigenetic predictor of PAI-1 levels (DNAm PAI-1) were determined for study participants from 3 population-based cohort studies. Cox models evaluated for associations with incident AF and results were combined via random-effects meta-analysis. Two-sample summary-level Mendelian randomization analyses evaluated for associations between genetic instruments of the EAA measures and AF.
Results:
Among 5,600 individuals (mean age: 65.5 years; 60.1% female; 50.7% black), there were 905 incident AF cases during a mean follow-up of 12.9 years. Unadjusted analyses revealed all 4 epigenetic clocks and the DNAm PAI-1 predictor were associated with statistically significant higher hazards of incident AF, though the magnitudes of their point estimates were smaller relative to the associations observed for chronological age. The pooled EAA estimates for each epigenetic measure, with the exception of Horvath EAA, were associated with incident AF in models adjusted for chronological age, race, sex, and smoking variables. Following multivariable adjustment for additional known AF risk factors that could also potentially function as mediators, pooled EAA measures for 2 clocks remained statistically significant. Five year increases in EAA measures for DNAm GrimAge and DNAm PhenoAge were associated with 19% (adjusted hazard ratio [HR]: 1.19; 95% confidence intervals [CI]: 1.09-1.31; p<0.01) and 15% (adjusted HR: 1.15; 95% CI: 1.05-1.25; p<0.01) higher hazards of incident AF, respectively. Mendelian randomization analyses for the 5 EAA measures did not reveal statistically significant associations with AF. Conclusions: Our study identified adjusted associations between EAA measures and incident AF, suggesting biological aging plays an important role independent of chronological age, though a potential underlying causal relationship remains unclear. These aging processes may be modifiable and not constrained by the immutable factor of time.




Circulation: 29 Sep 2021; epub ahead of print
Roberts JD, Vittinghoff E, Lu AT, Alonso A, ... Horvath S, Marcus GM
Circulation: 29 Sep 2021; epub ahead of print | PMID: 34587750
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Abstract

Bleeding risk with rivaroxaban compared with vitamin K antagonists in patients aged 80 years or older with atrial fibrillation.

Hanon O, Vidal JS, Pisica-Donose G, Orvoën G, ... Boureau AS, SAFIR study group
Objective
Direct oral anticoagulants have been evaluated in the general population, but proper evidence for their safe use in the geriatric population is still missing. We compared the bleeding risk of a direct oral anticoagulant (rivaroxaban) and vitamin K antagonists (VKAs) among French geriatric patients with non-valvular atrial fibrillation (AF) aged ≥80 years.
Methods
We performed a sequential observational prospective cohort study, using data from 33 geriatric centres. The sample comprised 908 patients newly initiated on VKAs between September 2011 and September 2014 and 995 patients newly initiated on rivaroxaban between September 2014 and September 2017. Patients were followed up for up to 12 months. One-year risks of major, intracerebral, gastrointestinal bleedings, ischaemic stroke and all-cause mortality were compared between rivaroxaban-treated and VKA-treated patients with propensity score matching and Cox models.
Results
Major bleeding risk was significantly lower in rivaroxaban-treated patients (7.4/100 patient-years) compared with VKA-treated patients (14.6/100 patient-years) after multivariate adjustment (HR 0.66; 95% CI 0.43 to 0.99) and in the propensity score-matched sample (HR 0.53; 95% CI 0.33 to 0.85). Intracerebral bleeding occurred less frequently in rivaroxaban-treated patients (1.3/100 patient-years) than in VKA-treated patients (4.0/100 patient-years), adjusted HR 0.59 (95% CI 0.24 to 1.44) and in the propensity score-matched sample HR 0.26 (95% CI 0.09 to 0.80). Major lower bleeding risk was largely driven by lower risk of intracerebral bleeding.
Conclusions
Our study findings indicate that bleeding risk, largely driven by lower risk of intracerebral bleeding, is lower with rivaroxaban than with VKA in stroke prevention in patients ≥80 years old with non-valvular AF.

© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 29 Sep 2021; 107:1376-1382
Hanon O, Vidal JS, Pisica-Donose G, Orvoën G, ... Boureau AS, SAFIR study group
Heart: 29 Sep 2021; 107:1376-1382 | PMID: 33262185
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Abstract

Catheter ablation as first-line treatment for paroxysmal atrial fibrillation: a systematic review and meta-analysis.

Imberti JF, Ding WY, Kotalczyk A, Zhang J, ... Andrade J, Gupta D
Objective
To assess the efficacy and safety of catheter ablation (CA) compared with antiarrhythmic drugs (AADs) as first-line treatment for symptomatic paroxysmal atrial fibrillation (AF).
Methods
Systematic review and meta-analysis of randomised controlled trials identified using MEDLINE, Cochrane Library and Embase published between 01/01/2000 and 19/03/2021. The primary efficacy endpoint was the first documented recurrence of atrial arrhythmias following the blanking period. The primary safety endpoint was a composite of all serious adverse events (SAEs).
Results
From 441 records, 6 studies met the inclusion criteria. 609 patients received CA, while 603 received AAD therapy. 212/609 patients in the CA group had a recurrence of atrial arrhythmias as compared with 318/603 in the AADs group resulting in a 36% relative risk reduction (risk ratio: 0.64, 95% CI 0.51 to 0.80, p<0.01). The risk of all SAEs was not statistically different between CA and AAD (0.87, 0.58 to 1.30, p=0.49); 107/609 SAE in the CA group vs 126/603 in the AAD group. Both recurrence of symptomatic atrial arrhythmias (109/505 vs 186/504) and healthcare utilisation (126/397 vs 185/394) were significantly lower in the CA group (0.53, 0.35 to 0.79 and 0.65, 0.48 to 0.89, respectively). There was a 79% reduction in the crossover rate during follow-up among patients randomised to CA compared with AAD (0.21, 0.13 to 0.32, p<0.01).
Conclusions
First-line treatment with CA is superior to AAD therapy in patients with symptomatic paroxysmal AF, as it significantly reduces the recurrence of any atrial arrhythmias and symptomatic atrial arrhythmias, and healthcare resource utilisation with comparable safety profile.

© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 29 Sep 2021; 107:1630-1636
Imberti JF, Ding WY, Kotalczyk A, Zhang J, ... Andrade J, Gupta D
Heart: 29 Sep 2021; 107:1630-1636 | PMID: 34261737
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Abstract

Anticoagulant prescribing for atrial fibrillation and risk of incident dementia.

Cadogan SL, Powell E, Wing K, Wong AY, Smeeth L, Warren-Gash C
Objective
The aim of this study was to investigate the association between oral anticoagulant type (direct oral anticoagulants (DOACs) vs vitamin K antagonists (VKAs)) and incident dementia or mild cognitive impairment (MCI) among patients with newly diagnosed atrial fibrillation (AF).
Methods
Using linked electronic health record (EHR) data from the Clinical Practice Research Datalink in the UK, we conducted a historical cohort study among first-time oral anticoagulant users with incident non-valvular AF diagnosed from 2012 to 2018. We compared the incidence of (1) clinically coded dementia and (2) MCI between patients prescribed VKAs and DOACs using Cox proportional hazards regression models, with age as the underlying timescale, accounting for calendar time and time on treatment, sociodemographic and lifestyle factors, clinical comorbidities and medications.
Results
Of 39 200 first-time oral anticoagulant users (44.6% female, median age 76 years, IQR 68-83), 20 687 (53%) were prescribed a VKA and 18 513 (47%) a DOAC at baseline. Overall, 1258 patients (3.2%) had GP-recorded incident dementia, incidence rate 16.5 per 1000 person-years. DOAC treatment for AF was associated with a 16% reduction in dementia diagnosis compared with VKA treatment in the whole cohort (adjusted HR 0.84, 95% CI: 0.73 to 0.98) and with a 26% reduction in incident MCI (adjusted HR 0.74, 95% CI: 0.65 to 0.84). Findings were similar across various sensitivity analyses.
Conclusions
Incident EHR-recorded dementia and MCI were less common among patients prescribed DOACs for new AF compared with those prescribed VKAs.

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.

Heart: 12 Oct 2021; epub ahead of print
Cadogan SL, Powell E, Wing K, Wong AY, Smeeth L, Warren-Gash C
Heart: 12 Oct 2021; epub ahead of print | PMID: 34645643
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Abstract

Ischemic Stroke in Patients With Hypertrophic Cardiomyopathy According to Presence or Absence of Atrial Fibrillation.

Fauchier L, Bisson A, Bodin A, Herbert J, ... Babuty D, Lip GYH
Background:
and purpose
Patients with hypertrophic cardiomyopathy (HCM) have high risk of ischemic stroke (IS), especially if atrial fibrillation (AF) is present. Improvements in risk stratification are needed to help identify those patients with HCM at higher risk of stroke, whether AF is present or not.
Methods
This French longitudinal cohort study from the database covering hospital care from 2010 to 2019 analyzed adults hospitalized with isolated HCM. A logistic regression model was used to construct a French HCM score, which was compared with the HCM Risk-CVA and CHA2DS2-VASc scores using c-indexes and calibration analysis.
Results
In 32 206 patients with isolated HCM, 12 498 (38.8%) had AF, and 2489 (7.7%) sustained an IS during follow-up. AF in patients with HCM was independently associated with a higher risk for death (hazard ratio, 1.129 [95% CI, 1.088-1.172]), cardiovascular death (hazard ratio, 1.254 [95% CI, 1.177-1.337]), IS (hazard ratio, 1.210 [95% CI, 1.111-1.317]), and other major cardiovascular events. Independent predictors of IS in HCM were older age, heart failure, AF, prior IS, smoking and poor nutrition (all P<0.05). For the HCM Risk-CVA score, CHA2DS2-VASc score and a French HCM score, all c-indexes were 0.65 to 0.70, with good calibration. Among patients with AF, the CHA2DS2-VASc score had marginal improvement over the HCM Risk-CVA score but was less predictive compared with the French HCM score (P=0.001). In patients without AF, both HCM Risk-CVA score and the French HCM score had significantly better prediction compared with CHA2DS2-VASc (both P<0.0001). Decision curve analysis demonstrated that the French HCM score had the best clinical usefulness of the 3 tested risk scores.
Conclusions
Patients with HCM have a high prevalence of AF and a significant risk of IS, and the presence of AF in patients with HCM was independently associated with worse outcomes. A simple French HCM score shows good prediction of IS in patients with HCM and clinical usefulness, with good calibration.



Stroke: 03 Oct 2021:STROKEAHA121034213; epub ahead of print
Fauchier L, Bisson A, Bodin A, Herbert J, ... Babuty D, Lip GYH
Stroke: 03 Oct 2021:STROKEAHA121034213; epub ahead of print | PMID: 34601900
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Abstract

Inducibility, but not stability, of atrial fibrillation is increased by NOX2 overexpression in mice.

Mighiu AS, Recalde A, Ziberna K, Carnicer R, ... Simon JN, Casadei B
Aims
Gp91-containing NADPH oxidases (NOX2) are a significant source of myocardial superoxide production. An increase in NOX2 activity accompanies atrial fibrillation (AF) induction and electrical remodelling in animal models and predicts incident AF in humans; however, a direct causal role for NOX2 in AF has not been demonstrated. Accordingly, we investigated whether myocardial NOX2 overexpression in mice (NOX2-Tg) is sufficient to generate a favourable substrate for AF and further assessed the effects of atorvastatin, an inhibitor of NOX2, on atrial superoxide production and AF susceptibility.
Methods and results
NOX2-Tg mice showed a 2- to 2.5-fold higher atrial protein content of NOX2 compared with wild-type (WT) controls, which was associated with a significant (twofold) increase in NADPH-stimulated superoxide production (2-hydroxyethidium by HPLC) in left and right atrial tissue homogenates (P = 0.004 and P = 0.019, respectively). AF susceptibility assessed in vivo by transoesophageal atrial burst stimulation was modestly increased in NOX2-Tg compared with WT (probability of AF induction: 88% vs. 69%, respectively; P = 0.037), in the absence of significant alterations in AF duration, surface ECG parameters, and LV mass or function. Mechanistic studies did not support a role for NOX2 in promoting electrical or structural remodelling, as high-resolution optical mapping of atrial tissues showed no differences in action potential duration and conduction velocity between genotypes. In addition, we did not observe any genotype difference in markers of fibrosis and inflammation, including atrial collagen content and Col1a1, Il-1β, Il-6, and Mcp-1 mRNA. Similarly, NOX2 overexpression did not have consistent effects on RyR2 Ca2+ leak nor did it affect PKA or CaMKII-mediated RyR2 phosphorylation. Finally, treatment with atorvastatin significantly inhibited atrial superoxide production in NOX2-Tg but had no effect on AF induction in either genotype.
Conclusion
Together, these data indicate that while atrial NOX2 overexpression may contribute to atrial arrhythmogenesis, NOX2-derived superoxide production does not affect the electrical and structural properties of the atrial myocardium.

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

Cardiovasc Res: 27 Sep 2021; 117:2354-2364
Mighiu AS, Recalde A, Ziberna K, Carnicer R, ... Simon JN, Casadei B
Cardiovasc Res: 27 Sep 2021; 117:2354-2364 | PMID: 33483749
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Abstract

Aspirin versus P2Y inhibitors with anticoagulation therapy for atrial fibrillation.

Fukaya H, Ako J, Yasuda S, Kaikita K, ... Matsui K, Ogawa H
Objective
Patients with coronary artery disease (CAD) and atrial fibrillation (AF) can be treated with multiple antithrombotic therapies including antiplatelet and anticoagulant therapies; however, this has the potential to increase bleeding risk. Here, we aimed to evaluate the efficacy and safety of P2Y12 inhibitors and aspirin in patients also receiving anticoagulant therapy.
Methods
We evaluated patients from the Atrial Fibrillation and Ischaemic Events with Rivaroxaban in Patients with Stable Coronary Artery Disease (AFIRE) trial who received rivaroxaban plus an antiplatelet agent; the choice of antiplatelet agent was left to the physician\'s discretion. The primary efficacy and safety end points, consistent with those of the AFIRE trial, were compared between P2Y12 inhibitors and aspirin groups. The primary efficacy end point was a composite of stroke, systemic embolism, myocardial infarction, unstable angina requiring revascularisation or death from any cause. The primary safety end point was major bleeding according to the International Society on Thrombosis and Haemostasis criteria.
Results
A total of 1075 patients were included (P2Y12 inhibitor group, n=297; aspirin group, n=778). Approximately 60% of patients were administered proton pump inhibitors (PPIs) and there was no significant difference in PPI use in the groups. There were no significant differences in the primary end points between the groups (efficacy: HR 1.31; 95% CI 0.88 to 1.94; p=0.178; safety: HR 0.79; 95% CI 0.43 to 1.47; p=0.456).
Conclusions
There were no significant differences in cardiovascular and bleeding events in patients with AF and stable CAD taking rivaroxaban with P2Y12 inhibitors or aspirin in the chronic phase.
Trial registration number
UMIN000016612; NCT02642419.

© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 30 Oct 2021; 107:1731-1738
Fukaya H, Ako J, Yasuda S, Kaikita K, ... Matsui K, Ogawa H
Heart: 30 Oct 2021; 107:1731-1738 | PMID: 34261738
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Abstract

Prediction of incident atrial fibrillation in community-based electronic health records: a systematic review with meta-analysis.

Nadarajah R, Alsaeed E, Hurdus B, Aktaa S, ... Wu J, Gale CP
Objective
Atrial fibrillation (AF) is common and is associated with an increased risk of stroke. We aimed to systematically review and meta-analyse multivariable prediction models derived and/or validated in electronic health records (EHRs) and/or administrative claims databases for the prediction of incident AF in the community.
Methods
Ovid Medline and Ovid Embase were searched for records from inception to 23 March 2021. Measures of discrimination were extracted and pooled by Bayesian meta-analysis, with heterogeneity assessed through a 95% prediction interval (PI). Risk of bias was assessed using Prediction model Risk Of Bias ASsessment Tool and certainty in effect estimates by Grading of Recommendations, Assessment, Development and Evaluation.
Results
Eleven studies met inclusion criteria, describing nine prediction models, with four eligible for meta-analysis including 9 289 959 patients. The CHADS (Congestive heart failure, Hypertension, Age>75, Diabetes mellitus, prior Stroke or transient ischemic attack) (summary c-statistic 0.674; 95% CI 0.610 to 0.732; 95% PI 0.526-0.815), CHA2DS2-VASc (Congestive heart failure, Hypertension, Age>75 (2 points), Stroke/transient ischemic attack/thromboembolism (2 points), Vascular disease, Age 65-74, Sex category) (summary c-statistic 0.679; 95% CI 0.620 to 0.736; 95% PI 0.531-0.811) and HATCH (Hypertension, Age, stroke or Transient ischemic attack, Chronic obstructive pulmonary disease, Heart failure) (summary c-statistic 0.669; 95% CI 0.600 to 0.732; 95% PI 0.513-0.803) models resulted in a c-statistic with a statistically significant 95% PI and moderate discriminative performance. No model met eligibility for inclusion in meta-analysis if studies at high risk of bias were excluded and certainty of effect estimates was \'low\'. Models derived by machine learning demonstrated strong discriminative performance, but lacked rigorous external validation.
Conclusions
Models externally validated for prediction of incident AF in community-based EHR demonstrate moderate predictive ability and high risk of bias. Novel methods may provide stronger discriminative performance.
Systematic review registration
PROSPERO CRD42021245093.

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.

Heart: 03 Oct 2021; epub ahead of print
Nadarajah R, Alsaeed E, Hurdus B, Aktaa S, ... Wu J, Gale CP
Heart: 03 Oct 2021; epub ahead of print | PMID: 34607811
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Abstract

Genetic inhibition of Nuclear Factor of Activated T-cell c2 (NFATc2) prevents atrial fibrillation in CREM transgenic mice.

Ni L, Lahiri SK, Nie J, Pan X, ... Dobrev D, Wehrens XHT
Aims
Abnormal intracellular calcium handling contributes to the progressive nature of atrial fibrillation (AF), the most common sustained cardiac arrhythmia. Evidence in mouse models suggests that activation of the nuclear factor of activated T-cell (NFAT) signaling pathway contributes to atrial remodeling. Our aim was to determine the role of NFATc2 in AF in humans and mouse models.
Methods and results
Expression levels of NFATc1-c4 isoforms were assessed by quantitative reverse transcription-polymerase chain reaction in right atrial appendages from patients with chronic AF. NFATc1 and NFATc2 mRNA levels were elevated in chronic AF (cAF) patients compared with those in sinus rhythm (SR). Western blotting revealed increased cytosolic and nuclear levels of NFATc2 in AF patients. Similar findings were obtained in CREM-IbΔC-X transgenic (CREM) mice, a model of progressive AF. Telemetry ECG recordings revealed age-dependent spontaneous AF in CREM mice, which was prevented by NFATc2 knockout in CREM: NFATc2-/- mice. Programmed electrical stimulation revealed that CREM: NFATc2-/- mice lacked an AF substrate. Morphometric analysis and histology revealed increased atrial weight and atrial fibrosis in CREM mice compared with WT controls, which was reversed in CREM: NFATc2-/- mice. Confocal microscopy showed an increased Ca2+ spark frequency despite a reduced sarcoplasmic reticulum (SR) Ca2+ load in CREM mice compared with controls, whereas these abnormalities were normalized in CREM: NFATc2-/- mice. Western blotting revealed that genetic inhibition of Ca2+/calmodulin-dependent protein kinase II-mediated phosphorylation of S2814 on RyR2 in CREM: RyR2-S2814A mice suppressed NFATc2 activation observed in CREM mice, suggesting that NFATc2 is activated by excessive SR Ca2+ leak via RyR2. Finally, chromatin immunoprecipitation sequencing from AF patients identified Ras And EF-Hand Domain-Containing Protein (RASEF) as a direct target of NFATc2 mediated transcription.
Conclusion
Our findings reveal activation of the NFAT signaling pathway in patients of Chinese and European descent. NFATc2 knockout prevents the progression of AF in the CREM mouse model.
Translational perspective
Atrial fibrillation (AF) is a progressive disease characterized by electrical and structural remodeling which promotes atrial arrhythmias. This study provides evidence for increased \'nuclear factor of activated T-cell\' (NFAT) signaling in patients with chronic AF. Studies in the CREM transgenic model of progressive AF revealed that the NFATc2 isoform mediates atrial remodeling associated with AF substrate development. Chromatin immunoprecipitation sequencing of atrial biopsies from AF patients identified \'Ras And EF-Hand Domain-Containing Protein\' (RASEF) as a downstream target of NFATc2-mediated transcription, suggesting that targeting these factors might be beneficial for curtailing AF progression.

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

Cardiovasc Res: 13 Oct 2021; epub ahead of print
Ni L, Lahiri SK, Nie J, Pan X, ... Dobrev D, Wehrens XHT
Cardiovasc Res: 13 Oct 2021; epub ahead of print | PMID: 34648001
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Impact:
Abstract

Nonvalvular atrial fibrillation patients anticoagulated with rivaroxaban compared with warfarin exhibit reduced circulating extracellular vesicles with attenuated pro-inflammatory protein signatures.

Weiss L, Keaney J, Szklanna PB, Prendiville T, ... Ní Áinle F, Maguire PB
Background
Rivaroxaban, a direct oral factor Xa inhibitor, mediates anti-inflammatory and cardiovascular-protective effects besides its well-established anticoagulant properties; however, these remain poorly characterized. Extracellular vesicles (EVs) are important circulating messengers regulating a myriad of biological and pathological processes and may be highly relevant to the pathophysiology of atrial fibrillation as they reflect alterations in platelet and endothelial biology. However, the effects of rivaroxaban on circulating pro-inflammatory EVs remain unknown.
Objectives
We hypothesized that rivaroxaban\'s anti-inflammatory properties are reflected upon differential molecular profiles of circulating EVs.
Methods
Differences in circulating EV profiles were assessed using a combination of single vesicle analysis by Nanoparticle Tracking Analysis and flow cytometry, and proteomics.
Results
We demonstrate, for the first time, that rivaroxaban-treated non-valvular atrial fibrillation (NVAF) patients (n=8) exhibit attenuated inflammation compared with matched warfarin controls (n=15). Circulating EV profiles were fundamentally altered. Moreover, quantitative proteomic analysis of enriched plasma EVs from six pooled biological donors per treatment group revealed a profound decrease in highly pro-inflammatory protein expression and complement factors, together with increased expression of negative regulators of inflammatory pathways. Crucially, a reduction in circulating levels of soluble P-selectin was observed in rivaroxaban-treated patients (compared with warfarin controls), which negatively correlated with the patient\'s time on treatment.
Conclusion
Collectively, these data demonstrate that NVAF patients anticoagulated with rivaroxaban (compared with warfarin) exhibit both a reduced pro-inflammatory state and evidence of reduced endothelial activation. These findings are of translational relevance toward characterizing the anti-inflammatory and cardiovascular-protective mechanisms associated with rivaroxaban therapy.

© 2021 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis.

J Thromb Haemost: 29 Sep 2021; 19:2583-2595
Weiss L, Keaney J, Szklanna PB, Prendiville T, ... Ní Áinle F, Maguire PB
J Thromb Haemost: 29 Sep 2021; 19:2583-2595 | PMID: 34161660
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Impact:
Abstract

Atrial fibrillation following transcatheter atrial septal defect closure: a systematic review and meta-analysis.

Himelfarb JD, Shulman H, Olesovsky CJ, Rumman RK, ... Horlick E, Abrahamyan L
Objective
The ostium secundum atrial septal defect (ASD) is among the most common congenital cardiac anomalies diagnosed in adulthood. A known complication of transcatheter ASD closure is the development of new-onset atrial fibrillation and flutter (AFi/AFl). These arrhythmias confer an increased risk of postoperative stroke, thrombus formation and systemic emboli. This systematic review examines the burden of de novo AFi/AFl in adults following transcatheter closure and seeks to identify risk factors for AFi/AFl development.
Methods
Studies were identified by a search of MEDLINE, EMBASE and Cochrane databases from inception until 29 April 2020. A meta-analysis of AFi/AFl incidence was performed using a random-effects model.
Results
A total of 31 studies met inclusion criteria, comprising 4788 adult patients without a history of AFi/AFl. Twenty-three studies were included in quantitative synthesis and demonstrated an overall incidence rate of 1.82 patients per 100 person-years of follow-up (I2=83%). In studies that enrolled only patients ≥60 years old, the incidence was 5.21 patients per 100 person-years (I2=0%). Studies with follow-up duration ≤2 years reported an incidence of 4.05 per 100 person-years (I2=55%) compared with a rate of 1.19 per 100 person-years (I2=85%) for studies with follow-up duration >2 years.
Conclusions
The incidence of new-onset AFi/AFl is relatively low following transcatheter closure of secundum ASDs. The rate of de novo AFi/AFl, however, was significantly higher in elderly patients. Shorter follow-up time was associated with a higher reported incidence of AFi/AFl.

© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 20 Oct 2021; epub ahead of print
Himelfarb JD, Shulman H, Olesovsky CJ, Rumman RK, ... Horlick E, Abrahamyan L
Heart: 20 Oct 2021; epub ahead of print | PMID: 34675040
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Impact:
Abstract

Pathophysiological pathways in patients with heart failure and atrial fibrillation.

Santema BT, Arita VA, Sama IE, Kloosterman M, ... Rienstra M, Voors AA
Aims
Atrial fibrillation (AF) and heart failure (HF) are two growing epidemics that frequently co-exist. We aimed to gain insights into underlying pathophysiological pathways in HF patients with AF by comparing circulating biomarkers using pathway overrepresentation analyses.
Methods and results
From a panel of 92 biomarkers from different pathophysiological domains available in 1,620 patients with HF, we first tested which biomarkers were dysregulated in patients with HF and AF (n = 648) compared with patients in sinus rhythm (n = 972). Secondly, pathway overrepresentation analyses were performed to identify biological pathways linked to higher plasma concentrations of biomarkers in patients who had HF and AF. Findings were validated in an independent HF cohort (n = 1,219, 38% with AF). Patient with AF and HF were older, less often women, and less often had a history of coronary artery disease compared with those in sinus rhythm. In the index cohort, 24 biomarkers were upregulated in patients with AF and HF. In the validation cohort, 8 biomarkers were upregulated, which all overlapped with the 24 biomarkers found in the index cohort. The strongest up-regulated biomarkers in patients with AF were spondin-1 (fold change 1.18, p = 1.33x10-12), insulin-like growth factor-binding protein-1 (fold change 1.32, p = 1.08x10-8), and insulin-like growth factor-binding protein-7 (fold change 1.33, p = 1.35x10-18). Pathway overrepresentation analyses revealed that the presence of AF was associated with activation amyloid-beta metabolic processes, amyloid-beta formation, and amyloid precursor protein catabolic processes with a remarkable consistency observed in the validation cohort.
Conclusion
In two independent cohorts of patients with HF, the presence of AF was associated with activation of three pathways related to amyloid-beta. These hypothesis-generating results warrant confirmation in future studies.
Translational perspective
Using an unbiased approach, we identified and validated dysregulation of three amyloid-beta related pathways in patients who had heart failure (HF) with concomitant atrial fibrillation (AF). Amyloid-beta depositions are a hallmark of Alzheimer\'s disease, but might also play a role in pathophysiological processes outside the central nervous system. Biopsy studies are needed to confirm the pathophysiological role of amyloid-beta in patients with AF and HF. Diagnostic and therapeutic implications should be investigated in the light of potential pathophysiological overlap between the three aging-related epidemics: Alzheimer\'s disease, AF and HF.

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

Cardiovasc Res: 22 Oct 2021; epub ahead of print
Santema BT, Arita VA, Sama IE, Kloosterman M, ... Rienstra M, Voors AA
Cardiovasc Res: 22 Oct 2021; epub ahead of print | PMID: 34687289
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Impact:
Abstract

Multiplex protein screening of biomarkers associated with major bleeding in patients with atrial fibrillation treated with oral anticoagulation.

Siegbahn A, Lindbäck J, Hijazi Z, Åberg M, ... Yusuf S, Wallentin L
Background
Oral anticoagulants (OAC) in patients with atrial fibrillation (AF) prevent thromboembolic events, but are associated with significant risk of bleeding.
Objectives
To explore associations between a wide range of biomarkers and bleeding risk in patients with AF on OAC.
Method
Biomarkers were analyzed in a random sample of 4200 patients, 204 cases with major bleedings, from ARISTOTLE. The replication cohort included 344 cases with major bleeding and 1024 random controls from RE-LY. Plasma samples obtained at randomization were analyzed by the Olink Proximity Extension Assay cardiovascular and inflammation panels and conventional immunoassays. The associations between biomarker levels and major bleeding over 1 to 3 years of follow-up were evaluated by random survival forest/Boruta analyses and Cox regression analyses to assess linear associations and hazard ratios for identified biomarkers.
Results
Out of 268 proteins, nine biomarkers were independently associated with bleeding in both cohorts. In the replication cohort the linear hazard ratios (95% confidence intervals) per interquartile range were for these biomarkers: TNF-R1 1.748 (1.456, 2.098), GDF-15 1.653 (1.377, 1.985), EphB4 1.575 (1.320, 1.880), suPAR 1.548 (1.294, 1.851), OPN 1.476 (1.240, 1.757), OPG 1.397 (1.156, 1.688), TNF-R2 1.360 (1.144,1.616), cTnT-hs 1.232 (1.067, 1.423), and TRAIL-R2 1.202 (1.069, 1.351).
Conclusions
In patients with AF on OAC, GDF-15, cTnT-hs, and seven novel biomarkers were independently associated with major bleedings and reflect pathophysiologic processes of inflammation, apoptosis, oxidative stress, vascular calcification, coagulation, and fibrinolysis. Investigations of the utility of these markers to refine risk stratification and guide the management of patients at high risk of bleeding are warranted.

© 2021 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis.

J Thromb Haemost: 30 Oct 2021; 19:2726-2737
Siegbahn A, Lindbäck J, Hijazi Z, Åberg M, ... Yusuf S, Wallentin L
J Thromb Haemost: 30 Oct 2021; 19:2726-2737 | PMID: 34390530
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Impact:
Abstract

Implementing Biological Pacemakers: Design Criteria for Successful.

Komosa ER, Wolfson DW, Bressan M, Cho HC, Ogle BM
Each heartbeat that pumps blood throughout the body is initiated by an electrical impulse generated in the sinoatrial node (SAN). However, a number of disease conditions can hamper the ability of the SAN\'s pacemaker cells to generate consistent action potentials and maintain an orderly conduction path, leading to arrhythmias. For symptomatic patients, current treatments rely on implantation of an electronic pacing device. However, complications inherent to the indwelling hardware give pause to categorical use of device therapy for a subset of populations, including pediatric patients or those with temporary pacing needs. Cellular-based biological pacemakers, derived in vitro or in situ, could function as a therapeutic alternative to current electronic pacemakers. Understanding how biological pacemakers measure up to the SAN would facilitate defining and demonstrating its advantages over current treatments. In this review, we discuss recent approaches to creating biological pacemakers and delineate design criteria to guide future progress based on insights from basic biology of the SAN. We emphasize the need for long-term efficacy in vivo via maintenance of relevant proteins, source-sink balance, a niche reflective of the native SAN microenvironment, and chronotropic competence. With a focus on such criteria, combined with delivery methods tailored for disease indications, clinical implementation will be attainable.



Circ Arrhythm Electrophysiol: 29 Sep 2021; 14:e009957
Komosa ER, Wolfson DW, Bressan M, Cho HC, Ogle BM
Circ Arrhythm Electrophysiol: 29 Sep 2021; 14:e009957 | PMID: 34592837
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Impact:
Abstract

Importance of the Activation Sequence of the His or Right Bundle for Diagnosis of Complex Tachycardia Circuits.

Viswanathan MN, Julie He B, Sung R, Hoffmayer KS, ... Jackman WM, Scheinman MM
In this review, we emphasize the unique value of recording the activation sequence of the His bundle or right bundle branch (RB) for diagnoses of various supraventricular and fascicular tachycardias. A close analysis of the His to RB (H-RB) activation sequence can help differentiate various forms of supraventricular tachycardias, namely atrioventricular nodal reentry tachycardia from concealed nodofascicular tachycardia, a common clinical dilemma. Furthermore, bundle branch reentry tachycardia and fascicular tachycardias often are included in the differential diagnosis of supraventricular tachycardia with aberrancy, and the use of this technique can help the operator make the distinction between supraventricular tachycardias and these other forms of ventricular tachycardias using the His-Purkinje system. We show that this technique is enhanced by the use of multipolar catheters placed to span the proximal His to RB position to record the activation sequence between proximal His potential to the distal RB potential. This allows the operator to fully analyze the activation sequence in sinus rhythm as compared to that during tachycardia and may help target ablation of these arrhythmias. We argue that 3 patterns of H-RB activation are commonly identified-the anterograde H-RB pattern, the retrograde H-RB (right bundle to His bundle) pattern, and the chevron H-RB pattern (simultaneous proximal His and proximal RB activation)-and specific arrhythmias tend to be associated with specific H-RB activation sequences. We show that being able to record and categorize this H-RB relationship can be instrumental to the operator, along with standard pacing maneuvers, to make an arrhythmia diagnosis in complex tachycardia circuits. We highlight the importance of H-RB activation patterns in these complex tachycardias by means of case illustrations from our groups as well as from prior reports.



Circ Arrhythm Electrophysiol: 29 Sep 2021; 14:e009194
Viswanathan MN, Julie He B, Sung R, Hoffmayer KS, ... Jackman WM, Scheinman MM
Circ Arrhythm Electrophysiol: 29 Sep 2021; 14:e009194 | PMID: 34601885
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Impact:
Abstract

Brugada Syndrome: New Insights From Cardiac Magnetic Resonance and Electroanatomical Imaging.

Pappone C, Santinelli V, Mecarocci V, Tondi L, ... Camporeale A, Lombardi M
Background
Brugada syndrome (BrS) is considered a purely electrical disease with variable electrical substrates. Variable rates of mechanical abnormalities have been also reported. Whether exists a link between electrical and mechanical abnormalities has never been previously explored. This investigational physiopathological study aimed to determine the relationship between the substrate size/location, as exposed by ajmaline provocation, and the severity of mechanical abnormalities, as assessed by cardiac magnetic resonance in patients with BrS.
Methods
Twenty-four consecutive high-risk patients with BrS (mean age, 38±11 years, 17 males), presenting with malignant syncope and documented polymorphic VT/VF, and candidate to implantable cardioverter defibrillator implantation, underwent cardiac magnetic resonance and electroanatomic maps. During each examination, ajmaline test (1 mg/kg over 5 minutes) was performed. Cardiac magnetic resonance findings were compared with 24 age, sex, and body surface area-matched controls. In patients with BrS, the correlation between the electrical substrate extent and right ventricular regional mechanical abnormalities before/after ajmaline challenge was analyzed.
Results
After ajmaline, patients with BrS showed a reduction of right ventricular (RV) ejection fraction (P<0.001), associated with decreased transversal displacement (U, P<0.001) and longitudinal strain (ε, P<0.001) localized at RV outflow tract. In patients with BrS significant preajmaline/postajmaline changes of transversal displacement (ΔU, P<0.001) and longitudinal strain (Δε, P<0.001) were found. In the control group, no mechanical changes were observed after ajmaline. The electrical substrate consistently increased after ajmaline from 1.7±2.8 cm2 to 14.2±7.3 cm2 (P<0.001), extending from the RV outflow tract to the neighboring segments of the RV anterior wall. Postajmaline RV ejection fraction inversely correlated with postajmaline substrate extent (r=-0.830, P<0.001). In patients with BrS and normal controls, cardiac magnetic resonance detected neither myocardial fibrosis nor RV outflow tract morphological abnormalities.
Conclusions
BrS is a dynamic RV electromechanical disease, where functional abnormalities correlate with the maximal extent of the substrate size. These findings open new lights on the physiopathology of the disease.
Registration
URL: https://clinicaltrial.gov; Unique identifier: NCT03524079.



Circ Arrhythm Electrophysiol: 24 Oct 2021:CIRCEP121010004; epub ahead of print
Pappone C, Santinelli V, Mecarocci V, Tondi L, ... Camporeale A, Lombardi M
Circ Arrhythm Electrophysiol: 24 Oct 2021:CIRCEP121010004; epub ahead of print | PMID: 34693720
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Impact:
Abstract

Tachypacing-induced CREB/CD44 signaling contributes to the suppression of L-type calcium channel expression and the development of atrial remodeling.

Chang SH, Chan YH, Chen WJ, Chang GJ, Lee JL, Yeh YH
Background
Atrial fibrillation (AF), a common arrhythmia in clinics, is characterized as downregulation of L-type calcium channel (LTCC) and shortening of atrial action potential duration (APD). Our prior studies have shown the association of CD44 with AF genesis.
Objective
The purpose of this study was to explore the potential role of CD44 and its related signaling in tachypacing-induced downregulation of LTCC.
Methods and results
In vitro, tachypacing in atrium-derived myocytes (HL-1 cell line) induced activation (phosphorylation) of cyclic adenosine monophosphate response element-binding protein (CREB). Furthermore, tachypacing promoted an association between CREB and CD44 in HL-1 myocytes, which was documented in atrial tissues from patients with AF. Deletion and mutational analysis of the LTCC promoter along with chromatin immunoprecipitation revealed that cyclic adenosine monophosphate response element is essential for tachypacing-inhibited LTCC transcription. Tachypacing also hindered the binding of p-CREB to the promoter of LTCC. Blockade of CREB/CD44 signaling in HL-1 cells attenuated tachypacing-triggered downregulation of LTCC and shortening of APD. Atrial myocytes isolated from CD44-/- mice exhibited higher LTCC current and longer APD than did those from wild-type mice. Ex vivo, tachypacing caused less activation of CREB in CD44-/- mice than in wild-type mice. In vivo, burst atrial pacing stimulated less inducibility of AF in CREB inhibitor-treated mice than in controls.
Conclusion
Tachypacing-induced CREB/CD44 signaling contributes to the suppression of LTCC, which provides valuable information about the pathogenesis of atrial modeling and AF.

Copyright © 2021 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Heart Rhythm: 29 Sep 2021; 18:1760-1771
Chang SH, Chan YH, Chen WJ, Chang GJ, Lee JL, Yeh YH
Heart Rhythm: 29 Sep 2021; 18:1760-1771 | PMID: 34023501
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Impact:
Abstract

Simple electrophysiological predictor of QRS change induced by cardiac resynchronization therapy: A novel marker of complete left bundle branch block.

Sedláček K, Jansová H, Vančura V, Grieco D, Kautzner J, Wichterle D
Background
QRS complex shortening by cardiac resynchronization therapy (CRT) has been associated with improved outcomes.
Objective
We hypothesized that the absence of QRS duration (QRSd) prolongation by right ventricular mid-septal pacing (RVP) may indicate complete left bundle branch block (cLBBB).
Methods
We prospectively collected 12-lead surface electrocardiograms (ECGs) and intracardiac electrograms during CRT implant procedures. Digital recordings were edited and manually measured. The outcome measure was a change in QRSd induced by CRT (delta CRT). Several outcome predictors were investigated: native QRSd, cLBBB (by using Strauss criteria), interval between the onset of the QRS complex and the local left ventricular electrogram (Q-LV), and a newly proposed index defined by the difference between RVP and native QRSd (delta RVP).
Results
One hundred thirty-three consecutive patients were included in the study. Delta RVP was 27 ± 25 ms, and delta CRT was -14 ± 28 ms. Delta CRT correlated with native QRSd (r = -0.65), with the presence of ECG-based cLBBB (r = -0.40), with Q-LV (r = -0.68), and with delta RVP (r = 0.72) (P < .00001 for all correlations). In multivariable analysis, delta CRT was most strongly associated with delta RVP (P < .00001), followed by native QRSd and Q-LV, while ECG-based cLBBB became a nonsignificant factor.
Conclusion
Baseline QRSd, delta RVP, and LV electrical lead position (Q-LV) represent strong independent predictors of ECG response to CRT. The absence of QRSd prolongation by RVP may serve as an alternative and more specific marker of cLBBB. Delta RVP correlates strongly with the CRT effect on QRSd and outperforms the predictive value of ECG-based cLBBB.

Copyright © 2021 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Heart Rhythm: 29 Sep 2021; 18:1717-1723
Sedláček K, Jansová H, Vančura V, Grieco D, Kautzner J, Wichterle D
Heart Rhythm: 29 Sep 2021; 18:1717-1723 | PMID: 34098086
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Impact:
Abstract

Deficiency of CXXC finger protein 1 leads to small changes in heart rate but moderate epigenetic alterations and significant protein downregulation of hyperpolarization-activated cyclic nucleotide-gated 4 (HCN4) ion channels in mice.

Shi L, Shen J, Jin X, Li Z, ... Yang B, Pan Z
Background
The normal cardiac rhythm is generated in the sinoatrial node (SAN). Changes in ionic currents of the SAN may cause sinus arrhythmia. CXXC finger protein 1 (Cfp1) is an epigenetic regulator that is involved in transcriptional regulation of multiple genes.
Objective
The purpose of this study was to explore whether Cfp1 controls SAN function through regulation of ion channel-related genes.
Methods
Electrophysiological study, patch clamp recording, reverse transcriptase polymerase chain reaction, optical mapping, chromatin immunoprecipitation, and immunofluorescence staining were performed to evaluate the function of SAN and underlying mechanism on Cfp1 heterozygous knockout (Cfp1+/-) mice.
Results
Heart rate was slower slightly and SAN recovery time was longer in Cfp1+/- mice than controls. Whole-cell patch-clamp recording showed that the firing rate of action potentials was reduced in Cfp1+/- mice. The density of If current was reduced by 66% in SAN cells of Cfp1+/- mice but the densities of ICa, ICa-L, and ICa-T were not changed. The hyperpolarization-activated cyclic nucleotide-gated 4 (HCN4) mRNA level in SAN tissue of Cfp1+/- mice was reduced. The HCN4 protein was significantly decreased in SAN cells and tissues after heterozygous deletion of Cfp1. Chromatin immunoprecipitation assay on cultured HL-1 cells demonstrated that Cfp1 was enriched in the promoter regions of HCN4. Knockdown of Cfp1 reduced H3K4 trimethylation, H3K9 acetylation, and H3K27 acetylation of HCN4 promoter region.
Conclusion
Deficiency of Cfp1 leads to small changes in heart rate by moderate epigenetic modification alterations and significant protein downregulation of HCN4 ion channels in mice.

Copyright © 2021 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Heart Rhythm: 29 Sep 2021; 18:1780-1789
Shi L, Shen J, Jin X, Li Z, ... Yang B, Pan Z
Heart Rhythm: 29 Sep 2021; 18:1780-1789 | PMID: 34182171
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Impact:
Abstract

HIGH DENSITY EPICARDIAL MAPPING IN BRUGADA SYNDROME: DEPOLARIZATION AND REPOLARIZATION ABNORMALITIES.

Pannone L, Monaco C, Sorgente A, Vergara P, ... Chierchia GB, de Asmundis C
Background
The pathogenesis of Brugada syndrome (BrS) and consequently of abnormal electrograms (aEGMs) found in the epicardium of the right ventricular outflow tract (RVOT-EPI) is controversial.
Objective
This study aimed to analyze aEGM from high density RVOT-EPI mapping (EAM).
Methods
All patients undergoing RVOT-EPI EAM with HD-Grid Catheter for BrS were retrospectively included. Maps were acquired before and after ajmaline and all patients had concomitant non-invasive ECG imaging (ECGI) with annotation of RVOT-EPI latest activation time (RVOTat). High frequency potentials (HFPs) were defined as ventricular potentials occurring during or after the far-field ventricular EGM showing a local activation time (HFPat). Low frequency potentials (LFPs) were defined as aEGMs occurring after near field ventricular activation showing fractionation or delayed components; their activation time from surface ECG was defined as LFPat.
Results
Fifteen consecutive patients were included in the study. At EAM before ajmaline 7 patients (46.7%) showed LFPs. All patients showed HFPs before and after ajmaline and LFPs after ajmaline. Mean HFPat [134.4 ms vs 65.3 ms, p<0.001], mean LFPat [224.6 ms vs 113.6 ms, p<0.001] and mean RVOTat [124.8 ms vs 55.9 ms, p<0.001] increased after ajmaline. RVOTat correlated with HFPat before (ρ=0.76) and after ajmaline (ρ=0.82) while RVOTat was shorter than LFPat before (p<0.001) and after ajmaline (p<0.001). BrS patients with history of aborted sudden cardiac death had longer aEGMs after ajmaline.
Conclusion
Two different types of aEGMs are described from BrS high density epicardial mapping. This might correlate with depolarization and repolarization abnormalities.

Copyright © 2021. Published by Elsevier Inc.

Heart Rhythm: 29 Sep 2021; epub ahead of print
Pannone L, Monaco C, Sorgente A, Vergara P, ... Chierchia GB, de Asmundis C
Heart Rhythm: 29 Sep 2021; epub ahead of print | PMID: 34601129
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Impact:
Abstract

Sex differences in the origin of Purkinje ectopy-initiated idiopathic ventricular fibrillation.

Surget E, Cheniti G, Ramirez FD, Leenhardt A, ... Hocini M, Haïssaguerre M
Background
Purkinje ectopics (PurkEs) are major triggers of idiopathic ventricular fibrillation (VF). Identifying clinical factors associated with specific PurkE characteristics could yield insights into the mechanisms of Purkinje-mediated arrhythmogenicity.
Objective
The purpose of this study was to examine the associations of clinical, environmental, and genetic factors with PurkE origin in patients with PurkE-initiated idiopathic VF.
Methods
Consecutive patients with PurkE-initiated idiopathic VF from 4 arrhythmia referral centers were included. We evaluated demographic characteristics, medical history, clinical circumstances associated with index VF events, and electrophysiological characteristics of PurkEs. An electrophysiology study was performed in most patients to confirm the Purkinje origin.
Results
Eighty-three patients were included (mean age 38 ± 14 years; 44 [53%] women), of whom 32 had a history of syncope. Forty-four patients had VF at rest. PurkEs originated from the right ventricle (RV) in 41 patients (49%), from the left ventricle (LV) in 36 (44%), and from both ventricles in 6 (7%). Seasonal and circadian distributions of VF episodes were similar according to PurkE origin. The clinical characteristics of patients with RV vs LV PurkE origins were similar, except for sex. RV PurkEs were more frequent in men than in women (76% vs 24%), whereas LV and biventricular PurkEs were more frequent in women (81% vs 19% and 83% vs 17%, respectively) (P < .0001).
Conclusion
PurkEs triggering idiopathic VF originate dominantly from the RV in men and from the LV or both ventricles in women, adding to other sex-related arrhythmias such as Brugada syndrome or long QT syndrome. Sex-based factors influencing Purkinje arrhythmogenicity warrant investigation.

Copyright © 2021 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Heart Rhythm: 29 Sep 2021; 18:1647-1654
Surget E, Cheniti G, Ramirez FD, Leenhardt A, ... Hocini M, Haïssaguerre M
Heart Rhythm: 29 Sep 2021; 18:1647-1654 | PMID: 34260987
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Impact:
Abstract

Late arrhythmias in patients with new-onset persistent left bundle branch block after transcatheter aortic valve replacement using a balloon-expandable valve.

Muntané-Carol G, Nombela-Franco L, Serra V, Urena M, ... Philippon F, Rodés-Cabau J
Background
The arrhythmic burden after discharge in patients with new-onset left bundle branch block (LBBB) undergoing transcatheter aortic valve replacement (TAVR) with the balloon-expandable SAPIEN 3 (S3) valve remains largely unknown.
Objective
The purpose of this study was to determine the incidence of late arrhythmias in patients with new-onset LBBB undergoing TAVR with the balloon-expandable S3 valve.
Methods
This was a multicenter, prospective study that included 104 consecutive TAVR patients with new-onset persistent LBBB following TAVR with the S3 valve. An implantable cardiac monitor (Reveal XT, Reveal LINQ) was implanted before discharge. The primary endpoint was the incidence of high-degree atrioventricular block or complete heart block (HAVB/CHB).
Results
A total of 40 patients (38.5%) had at least 1 significant arrhythmic event, leading to a treatment change in 17 (42.5%). Significant bradyarrhythmias occurred in 20 of 104 patients (19.2%) (34 HAVB/CHB episodes, 252 severe bradycardia episodes), with 10 of 20 patients (50%) exhibiting at least 1 episode of HAVB/CHB. Most HAVB/CHB episodes (60%) occurred within 4 weeks after discharge. Nine patients (8.7%) underwent permanent pacemaker implantation at 12 months based on the Reveal findings (6 HAVB/CHB, 3 severe bradycardia).
Conclusion
S3 valve recipients with new-onset LBBB have a high arrhythmic burden, with more than one-third of patients exhibiting at least 1 significant arrhythmic episode within 12 months (HAVB/CHB in 10% of patients). About one-half of bradyarrhythmic events occurred within 4 weeks after discharge. These results should inform future strategies on the use of continuous electrocardiographic monitoring in TAVR S3 patients with new conduction disturbances following the procedure.

Copyright © 2021 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Heart Rhythm: 29 Sep 2021; 18:1733-1740
Muntané-Carol G, Nombela-Franco L, Serra V, Urena M, ... Philippon F, Rodés-Cabau J
Heart Rhythm: 29 Sep 2021; 18:1733-1740 | PMID: 34082083
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Impact:
Abstract

Identification of a SCN5A founder mutation causing sudden death, Brugada syndrome, and conduction blocks in Southern Italy.

Curcio A, Malovini A, Mazzanti A, Memmi M, ... Bellazzi R, Napolitano C
Background
The genetic architecture of Brugada syndrome (BrS) is emerging as an increasingly complex area of investigation. The identification of genetically homogeneous populations can provide mechanistic insights and improve genotype-phenotype correlation.
Objective
To characterize and define the clinical implications of a novel BrS founder mutation. Using a haplotype-based approach we investigated whether 2 SCN5A genetic variants could derive from founder events.
Methods
Single nucleotide polymorphisms were genotyped in 201 subjects, haplotypes reconstructed, and mutational age estimated. Clinical phenotypes and historical records were collected.
Results
A SCN5A variant (c.3352C>T; p.Gln1118Ter) was identified in 3 probands with BrS originating from south Italy. The same mutation was identified in a proband from central Italy and in 1 U.S. resident subject with Italian ancestry. The 5 individuals carried a common core haplotype, whose frequency was extremely low in local noncarrier probands and in population controls (0%-6.06%). The clinical presentation included multigenerational dominant transmission of Brugada electrocardiographic pattern, high incidence of sudden cardiac death (SCD), and cardiac conduction defects (CCD). We reconstructed 7-generation pedigrees with common geographic origin. Variant\'s age estimates suggested that origin of the p.Gln1118Ter dates back 76 generations (95% confidence interval: 28-200). A second SCN5A variant (c.5350G>A; p.Glu1784Lys) identified in the region did not show similar founder signal.
Conclusion
p.Gln1118Ter is a novel BrS/CCD/SCD founder mutation. We illustrate how these findings provide insights on the inheritance patterns and phenotypes associated with SCN5A mutation.

Copyright © 2021 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Heart Rhythm: 29 Sep 2021; 18:1698-1706
Curcio A, Malovini A, Mazzanti A, Memmi M, ... Bellazzi R, Napolitano C
Heart Rhythm: 29 Sep 2021; 18:1698-1706 | PMID: 34245912
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Impact:
Abstract

Disruption of Protein Quality Control of Human Ether-à-go-go Related Gene K Channel Results in Profound Long QT Syndrome.

Ledford HA, Ren L, Thai PN, Park S, ... Zhang XD, Chiamvimonvat N
Background
Long QT syndrome (LQTS) is a hereditary disease that predisposes patients to life-threatening cardiac arrhythmias and sudden cardiac death. Our previously study of human ether-à-go-go related gene (hERG)-encoded K+ channel (Kv11.1) supports an association between hERG and RING Finger Protein 207 (RNF207) variants in aggravating the onset and severity of LQTS, specifically T613M hERG (hERGT613M) and RNF207 frameshift (RNF207G603fs) mutations. However, the underlying mechanistic underpinning remains unknown.
Objective
The purpose of the current study is to test the role of RNF207 on the function of hERG-encoded K+ channel subunits.
Methods and results
Here, we demonstrate that RNF207 serves as an E3 ubiquitin ligase and targets misfolded hERGT613M proteins for degradation. RNF207G603fs exhibits decreased activity and hinders the normal degradation pathway; this increases the levels of hERGT613M subunits and their dominant-negative effect on the wild-type (WT) subunits, ultimately resulting in decreased current density. Similar findings are shown for hERGA614V, a known dominant-negative mutant subunit. Finally, the presence of RNF207G603fs with hERGT613M results in significantly prolonged action potential durations and reduced hERG current in human pluripotent stem cell-derived cardiomyocytes.
Conclusions
Our study establishes RNF207 as an interacting protein serving as a ubiquitin ligase for hERG-encoded K+ channel subunits. Normal function of RNF207 is critical for the quality control of hERG subunits and, consequently, cardiac repolarization. Moreover, our study provides evidence for protein quality control as a new paradigm in life-threatening cardiac arrhythmias in LQTS patients.

Copyright © 2021. Published by Elsevier Inc.

Heart Rhythm: 07 Oct 2021; epub ahead of print
Ledford HA, Ren L, Thai PN, Park S, ... Zhang XD, Chiamvimonvat N
Heart Rhythm: 07 Oct 2021; epub ahead of print | PMID: 34634443
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Impact:
Abstract

Comparison of Low and Full Dose Apixaban Versus Warfarin in Patients With Atrial Fibrillation and Renal Dysfunction (from a National Registry).

Gurevitz C, Giladi E, Barsheshet A, Klempfner R, ... Kornowski R, Elis A
The use of direct oral anticoagulants for stroke prevention in patients with non-valvular atrial fibrillation (NVAF) is robust. However, the efficacy and safety of different dosage in patients with renal dysfunction is still a clinical challenge. We aimed to evaluate the clinical characteristics and outcomes of patients treated with apixaban in its different doses. A multicenter prospective cohort study, where consecutive eligible apixaban or warfarin treated patients with NVAF and renal impairment, were registered. Patients were followed-up for clinical events over a mean period of 1 year. Analyses were performed according to the dose of apixaban given, with consideration to the standard indications for dose reduction. Primary outcome was a composite of 1-year mortality, stroke or systemic embolism, major bleeding and myocardial infarction, while secondary outcomes included those components separated. Among the study population (n = 2,140), risk of composite outcome was significantly lower in the high dose apixaban group (10%, n = 491) than the low dose group (18%, n = 673) and the warfarin group (18%, n = 976) p <0.001. Results of 1-year mortality were similar. Apixaban dosing analysis revealed 65% of patients were appropriately dosed, while 31% were under-dosed and 4% were over-dosed. Furthermore, 53% of patients treated with low dose apixaban were under-dosed. Propensity score analysis revealed that patients who were appropriately treated with low-dose apixaban had a trend towards better composite outcome and mortality than 1:1 matched warfarin treated patients (18% vs 24%, p = 0.09 and 16% vs 23%, p = 0.06, respectively). Overall, appropriately dosed apixaban treated patients at any dose had significantly better outcomes than matched warfarin treated patients (composite outcome probability of 13.1% vs 18.6%, p = 0.007). In conclusion, apixaban at any dose is a reasonable alternative to warfarin in patients with renal impairment, possibly associated with improved outcomes.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am J Cardiol: 14 Nov 2021; 159:87-93
Gurevitz C, Giladi E, Barsheshet A, Klempfner R, ... Kornowski R, Elis A
Am J Cardiol: 14 Nov 2021; 159:87-93 | PMID: 34503821
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Impact:
Abstract

Results and Predictive Factors After One Cryoablation for Persistent Atrial Fibrillation.

Hermida A, Diouf M, Kubala M, Fay F, ... Beyls C, Hermida JS
Cryoballoon pulmonary vein isolation (PVI) for persistent atrial fibrillation (AF) ablation is an increasingly used strategy. We aimed to determine the results and predictors of arrhythmia recurrence after a single procedure of cryoballoon PVI for patients with persistent and long-standing persistent AF. We included all consecutive patients who underwent cryoballoon PVI for the treatment of persistent symptomatic drug-refractory AF since 2012. All patients were prospectively followed to detect the recurrence of atrial tachyarrhythmia (ATa). Predictors of recurrence were assessed. Cryoballoon PVI was performed on 399 patients with persistent AF, among whom 52 (13%) had long-standing persistent AF. Patients with long-standing persistent AF had a significantly larger left atrium than those with persistent AF. A 28-mm cryoballoon was used for 322 patients (93%). In total, 359 patients (90%) completed the 12-month follow-up visit and the median follow-up was 24 months (interquartile range 43 to 13). The 2-year probability of freedom from ATa recurrence was 51% for persistent AF and 27% for long-standing persistent AF. Long-standing persistent AF and left atrial area/volume were independent predictors of ATa recurrence. Ten patients (2.5%) experienced phrenic nerve palsy, 1 tamponade (0.25%), 2 stroke (0.5%), 2 pericardial effusions (0.5%), and 5 vascular complications (1.25%). In conclusion, 2-year ATa-free survival rates were 51 and 27% for persistent and long-standing persistent AF patients, respectively. Complications were rare. Long-standing persistent AF and left-atrial area/volume were predictors of recurrence.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am J Cardiol: 14 Nov 2021; 159:65-71
Hermida A, Diouf M, Kubala M, Fay F, ... Beyls C, Hermida JS
Am J Cardiol: 14 Nov 2021; 159:65-71 | PMID: 34481590
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Abstract

Clinical characteristics and risk of arrhythmic events in patients younger than 12 years diagnosed with Brugada syndrome.

Righi D, Porco L, Calvieri C, Tamborrino PP, ... Tozzi AE, Drago F
Background
Brugada syndrome (BrS) is an inheritable disease with an increased risk of sudden cardiac death. Although several score systems have been proposed, the management of children with BrS has been inconsistently described.
Objective
The purpose of this study was to identify the characteristics, outcome, and risk factors associated with cardiovascular and arrhythmic events (AEs) in children younger than 12 years with BrS.
Methods
In this single-center case series, all children with spontaneous or drug/fever-induced type 1 Brugada electrocardiographic (ECG) pattern and younger than 12 years at the time of diagnosis were enrolled.
Results
Forty-three patients younger than 12 years at the time of diagnosis were included. The median follow-up was 3.97 years (interquartile range 2-12 years). In terms of first-degree atrioventricular block, premature beats, nonmalignant AEs, malignant AEs, and episodes of syncope, no significant differences were observed either between patients with spontaneous and drug/fever-induced type 1 Brugada ECG pattern or between female and male patients (except a significant difference between female and male patients for first-degree atrioventricular block). A higher incidence of malignant AEs was observed in patients with syncope (3 of 8 [37.5%] vs 0 of 35 [0%]; P = .005) than in patients without syncope. SCN5A mutations were associated with a higher occurrence of malignant AEs (3 of 14 [21.4%] vs 0 of 25 [0%]; P = .04) compared with no SCN5A mutations.
Conclusion
A spontaneous type 1 Brugada ECG pattern is not associated with a higher incidence of syncope, first-degree atrioventricular block, premature beats, nonmalignant AEs, and malignant AEs than the drug/fever-induced type 1 Brugada ECG pattern. Syncope events are correlated with an increased incidence of malignant AEs. Moreover, SCN5A mutations are associated with a higher occurrence of malignant AEs.

Copyright © 2021 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Heart Rhythm: 29 Sep 2021; 18:1691-1697
Righi D, Porco L, Calvieri C, Tamborrino PP, ... Tozzi AE, Drago F
Heart Rhythm: 29 Sep 2021; 18:1691-1697 | PMID: 34147702
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Impact:
Abstract

Long-term outcomes and periprocedural safety and efficacy of percutaneous left atrial appendage closure in a United Kingdom tertiary center: An 11-year experience.

Briosa E Gala A, Pope MTB, Monteiro C, Leo M, ... Newton JD, Betts TR
Background
Left atrial appendage occlusion (LAAO) has been widely adopted as a strategy for stroke prevention in patients with atrial fibrillation ineligible for oral anticoagulation.
Objective
The purpose of this study was to explore longer-term \"real-world\" safety and efficacy outcomes in patients undergoing LAAO given varied practices in antithrombotic regimens and adoption of same-day discharge.
Methods
Analysis of acute procedural and long-term outcome data was performed for all patients undergoing LAAO implant in a United Kingdom tertiary center over an 11-year period. Rates of adverse events were calculated and compared to predicted rates in historical cohorts according to CHA2DS2-VASc and HAS-BLED scores.
Results
Device implantation was attempted in 229 patients, with an acute procedural success rate of 98.2% and low rate of major procedural complications of 2.6% at 30 days, including 1.3% procedure-related mortality. In the last year of enrollment, 75% of patients were discharged on the same day of the procedure. A strategy of early cessation of antithrombotic therapy was adopted, with a low rate of device-related thrombus. Over total follow-up of 889 patient-years, there were low rates of thromboembolic events (2.2/100 patient-years) and of significant bleeding events (intracranial bleed 0.6/100 patient-years; nonprocedural major bleeding 2.3/100 patient-years).
Conclusion
LAAO with a same-day discharge strategy and early cessation of antiplatelet therapy seems to be safe and effective in reducing the risk of stroke and major bleeding over mean follow-up approaching 4 years. Although these data are reassuring, results from randomized trials with strict shorter periods of postprocedural antithrombotic therapy are eagerly awaited.

Copyright © 2021 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Heart Rhythm: 29 Sep 2021; 18:1724-1732
Briosa E Gala A, Pope MTB, Monteiro C, Leo M, ... Newton JD, Betts TR
Heart Rhythm: 29 Sep 2021; 18:1724-1732 | PMID: 34126270
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Impact:
Abstract

Electrophysiologic Characteristics of Atrial Tachycardia Recurrence: Relevance to Catheter Ablation Strategies in Adults with Congenital Heart Disease.

Moore JP, Burrows A, Gallotti RG, Shannon KM
Background
Catheter ablation outcomes for adults with congenital heart disease (ACHD) are described, but recurrence mechanisms remain largely unknown.
Objective
To identify the electrophysiologic characteristics of AT recurrence in ACHD.
Methods
ACHD atrial tachycardia (AT) procedures over a 10-year period were explored for AT or atrial fibrillation (AF) recurrence.
Results
At 299 procedures in 250 ACHD (mean age 39 +/- 15 years, 52% male), 464 ATs (360 intra-atrial reentrant tachycardia [IART], 104 focal AT [FAT], median 2 ATs/procedure) were targeted. Complete (n=256, 86%) or partial (n=37, 12%) success was achieved in 98% of procedures. Over 3.0 years, 67 patients (27%) developed AT/AF recurrence after the index procedure. Recurrent vs index tachycardias were more often FAT (38% vs 19%, p<0.001), demonstrated longer cycle length (325 vs 280 ms, p=0.003), required isoproterenol (50% vs 32%, p=.03) and involved the pulmonary venous atrium (PVA)/septum (53% vs 27%, p<0.001). AF history (HR 2.0 IQR 1.2-3.4, p=0.01), incomplete success (HR 3.6, IQR 2.1-6.4, p<0.001) and PVA substrate (HR 2.1 IQR 1.2-3.5, p=0.006) were independently associated with AT/AF recurrence. After complete index procedure success and no AF history, 5-year actuarial freedom from AT/AF and AT alone were 77% and 80%.
Conclusion
After catheter ablation in ACHD, repeat ATs were frequently focal, requiring isoproterenol administration, or involved IART within the PVA or atrial septum. Negative factors were partial success, index PVA substrate and remote history of AF. These data support aggressive, pharmacologic provocation to eliminate all inducible tachycardias and co-existing PVA substrates at index procedures for ACHD.

Copyright © 2021. Published by Elsevier Inc.

Heart Rhythm: 06 Oct 2021; epub ahead of print
Moore JP, Burrows A, Gallotti RG, Shannon KM
Heart Rhythm: 06 Oct 2021; epub ahead of print | PMID: 34628040
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Impact:
Abstract

Static magnetic field measurements of smart phones and watches and applicability to triggering magnet modes in implantable pacemakers and implantable cardioverter-defibrillators.

Seidman SJ, Guag J, Beard B, Arp Z
Background
Implantable pacemakers and implantable cardioverter-defibrillators (ICDs) are designed to include a \"magnet mode\" feature that can be activated from magnets stronger than 10 G. This feature is designed to be used when a patient is undergoing a procedure where electromagnetic interference is possible, or anytime suspension of tachycardia detection and therapy is needed. A publication in Heart Rhythm demonstrates an iPhone 12 triggering the magnet mode of a Medtronic ICD.
Objective
The purpose of this study is to determine the separation distance between consumer electronic devices that may create magnetic interference, including cell phones and smart watches, and implantable pacemakers and ICDs where magnet mode can be triggered.
Methods
The static magnetic fields of the iPhone 12 models and Apple Watch were measured at several planes in 1 cm resolution using an FW Bell 5180 Gauss Meter with STD18-0404 Transverse probe (unidirectional probe).
Results
All iPhone 12 and Apple Watch 6 models tested have static magnetic fields significantly greater than 10 G in close proximity (1-11 mm), which attenuates to below 10 G between 11 and 20 mm.
Conclusion
The findings of this study support the US Food and Drug Administration recommendation that patients keep any consumer electronic devices that may create magnetic interference, including cell phones and smart watches, at least 6 inches away from implanted medical devices, in particular pacemakers and cardiac defibrillators.

Published by Elsevier Inc.

Heart Rhythm: 29 Sep 2021; 18:1741-1744
Seidman SJ, Guag J, Beard B, Arp Z
Heart Rhythm: 29 Sep 2021; 18:1741-1744 | PMID: 34600610
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Abstract

Filamin C variant-associated Cardiomyopathy: A Pooled Analysis of Individual Patient Data to Evaluate the Clinical Profile and Risk of Sudden Cardiac Death.

Celeghin R, Cipriani A, Bariani R, Bueno Marinas M, ... Pilichou K, Bauce B
Background
Mutations in filamin-C (FLNC) are involved in the pathogenesis of arrhythmogenic cardiomyopathy (ACM) and dilated cardiomyopathy (DCM), and have been associated with a left ventricular (LV) phenotype, characterized by non-ischemic LV fibrosis, ventricular arrhythmias and sudden cardiac death (SCD).
Objective
To investigate the prevalence of FLNC variants in a gene-negative ACM population and to evaluate the clinical phenotype and SCD risk factors in FLNC-associated cardiomyopathies.
Methods
ACM probands who tested negative for mutations in ACM-related genes underwent FLNC genetic screening. Clinical and genetic data were collected and pooled together with those of previously published FLNC-ACM and FLNC-DCM patients.
Results
In a cohort of 270 gene-elusive ACM probands, 12 had FLNC variants (4.4%); thirteen additional family members carried the same mutation. Eighteen (72%) FLNC variant carriers had a diagnosis of ACM (72% males, mean age 45 y). On pooled analysis, 145 patients with FLNC-associated cardiomyopathies were included. Electrocardiographic (ECG) low QRS voltages were detected in 37%, T-wave inversion (TWI) in inferolateral/lateral leads in 24%. Among 67 patients who had cardiac magnetic resonance (CMR), LV non-ischemic late gadolinium enhancement (LGE) was found in 75%. SCD occurred in 28 (19%) patients, of whom 15 showed LV non-ischemic LGE/fibrosis. Compared with patients with no SCD, those who experienced SCD had more frequently inferolateral/lateral TWI (p=0.013) and LV LGE/fibrosis (p=0.033).
Conclusion
Clinical phenotype of FLNC-cardiomyopathies is characterized by late-onset presentation and typical ECG and CMR features. SCD is associated with the presence of LV LGE/fibrosis, but not with severe LV systolic dysfunction.

Copyright © 2021. Published by Elsevier Inc.

Heart Rhythm: 29 Sep 2021; epub ahead of print
Celeghin R, Cipriani A, Bariani R, Bueno Marinas M, ... Pilichou K, Bauce B
Heart Rhythm: 29 Sep 2021; epub ahead of print | PMID: 34601126
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Abstract

Atrial heat shock protein levels are associated with early postoperative and persistence of atrial fibrillation.

van Marion DMS, Ramos KS, Lanters EAH, Bulte LB, ... de Groot NMS, Brundel BJJM
Background
Early detection and staging of atrial fibrillation (AF) is of importance for clinical management. Serum (bio)markers, such as heat shock proteins (HSP), may enable AF staging and identify patients at risk for AF recurrence and postoperative AF (PoAF).
Objective
This study evaluates the relation between serum and atrial tissue HSP levels, stages of AF, AF recurrence after treatment, and PoAF from patients undergoing cardiothoracic surgery.
Methods
Patients without (control) and with paroxysmal, persistent (PerAF), or longstanding persistent (LSPerAF) AF were included. HSPB1, HSPA1, HSPB7, and HSPD1 levels were measured in serum obtained prior to and post intervention. HSPB1, HSPA1, HSPA5, HSPD1, HSPB5, and pHSF1 levels were measured in left and/or right atrial appendages (respectively, LAA and RAA).
Results
In RAA, HSPA5 levels were significantly lower in LSPerAF and HSPD1 levels significantly higher in PerAF patients compared to controls. In RAA of controls who developed PoAF, HSPA1 and HSPA5 levels were significantly higher compared to those without PoAF. Also, HSPB1 RAA levels were lower and HSPA5 LAA levels higher in patients undergoing arrhythmia surgery who developed AF recurrence within 1 week after surgery compared to patients who did not.
Conclusion
HSPA5 RAA and HSPD1 RAA and LAA levels are altered in persistent stages of AF. RAA HSPA1 and HSPA5 levels associate with development of PoAF. Additionally, HSPB1 RAA and HSPA5 LAA levels can predict AF recurrence in patients who underwent arrhythmia surgery. Nevertheless, HSP levels in serum cannot discriminate AF stages from controls, nor predict PoAF or AF recurrence after treatment.

Copyright © 2021 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Heart Rhythm: 29 Sep 2021; 18:1790-1798
van Marion DMS, Ramos KS, Lanters EAH, Bulte LB, ... de Groot NMS, Brundel BJJM
Heart Rhythm: 29 Sep 2021; 18:1790-1798 | PMID: 34186247
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Abstract

Safety, efficacy, and monitoring of bipolar radiofrequency ablation in beating myopathic human and healthy swine hearts.

Bhaskaran A, Niri A, Azam MA, Nayyar S, ... Ha A, Nanthakumar K
Background
The safety and efficacy parameters for bipolar radiofrequency (RF) ablation are not well defined.
Objective
The purpose of this study was to investigate the safe range of power, utility of transmyocardial bipolar electrogram (EGM) amplitude, and circuit impedance in ablation monitoring.
Methods
Sixteen beating ex vivo human and swine hearts were studied in a Langendorff setup. Ninety-two bipolar ablations using two 4-mm irrigated catheters were performed at settings of 20-50 W, 60 seconds, and 30 mL/min irrigation in the left ventricle.
Results
For low-power ablations (20 and 30 W), transmurality was observed in 29 of 38 (76%) and 10 of 28 (36%) ablations for tissue thickness ≤17 mm and >17 mm, respectively. For high-power ablations (40 and 50 W), transmurality was observed in 5 of 7 (71%) and 7 of 19 (37%) ablations for tissue thickness ≤17 mm and >17 mm, respectively. Steam pop occurrence for low- and high-power ablations was 11 of 66 (16%) and 16 of 26 (62%), respectively (P = .0001), respectively. Lesion depth (limited by transmurality) was 12.0 ± 5.7 mm and 12.3 ± 5.8 mm, respectively (P = 1). Transmyocardial EGM amplitude decrement >60% strongly predicted transmurality (area under the curve [AUC] 0.8), and circuit impedance decrement >26% predicted steam pops (AUC 0.75). Half-normal saline did not affect transmurality or incidence of steam pops compared to normal saline irrigation.
Conclusion
Bipolar RF ablation at power of 20-30 W provided an ideal balance of safety and efficacy, whereas power ≥40 W should be used with caution due to the high incidence of steam pops. Lesion transmurality monitoring and steam pop avoidance were best achieved using transmyocardial bipolar EGM voltage and circuit impedance, respectively.

Copyright © 2021 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Heart Rhythm: 29 Sep 2021; 18:1772-1779
Bhaskaran A, Niri A, Azam MA, Nayyar S, ... Ha A, Nanthakumar K
Heart Rhythm: 29 Sep 2021; 18:1772-1779 | PMID: 34182170
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Impact:
Abstract

Role of endocardial ablation in eliminating an epicardial arrhythmogenic substrate in patients with Brugada syndrome.

Kamakura T, Cochet H, Juhoor M, Nakatani Y, ... Haïssaguerre M, Hocini M
Background
Epicardial ablation is occasionally limited by coronary artery (CA) injuries or epicardial fat (EF).
Objective
The purpose of this study was to evaluate the anatomic obstacles that prevent ablation of epicardial abnormal potentials (EAPs) in patients with Brugada syndrome (BrS) and to investigate the feasibility of EAP elimination by endocardial right ventricular (RV) ablation.
Methods
This study included 16 BrS patients with previous ventricular fibrillation (VF), including 10 with an electrical storm. Data from multidetector computed tomography were assessed, and the proximity of the CA and EF was correlated with EAPs.
Results
EAPs were present in the epicardial RV outflow tract and RV inferior wall in all patients and 12 patients (75%), respectively. These EAPs were present within 5 mm of the main body and branches of the right CA in 14 patients (87.5%). However, only 1.4% ± 2.9% of the EAP area was covered with thick EF (≥8 mm). Partial EAP elimination by endocardial RV ablation was feasible in all 10 patients, with 53.3% successful endocardial RV radiofrequency applications for eliminating EAPs. After the procedure, VF remained inducible in 37.5% of the patients. During the 25.1 ± 29.1 months of follow-up, no patients experienced an electrical storm, and VF burden significantly decreased (median VF episodes before and after ablation: 7 and 0, respectively).
Conclusion
EAPs are near the CA in most BrS patients, thereby requiring caution during epicardial ablation, whereas EF is less of an issue. Endocardial ablation is feasible to eliminate some EAPs and may be combined with epicardial ablation.

Copyright © 2021 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Heart Rhythm: 29 Sep 2021; 18:1673-1681
Kamakura T, Cochet H, Juhoor M, Nakatani Y, ... Haïssaguerre M, Hocini M
Heart Rhythm: 29 Sep 2021; 18:1673-1681 | PMID: 34182174
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Abstract

Impact of a predefined pacemapping protocol use for ablation of infrequent premature ventricular complexes: A prospective, multicenter study.

Jáuregui B, Penela D, Fernández-Armenta J, Acosta J, ... Pedrote A, Berruezo A
Background
Pacemapping (PM) is a useful maneuver for aiding premature ventricular complex (PVC) ablation. Its standalone clinical value is still to be defined.
Objectives
The purpose of this study was to analyze the efficacy of a predefined PM protocol for low-burden PVC ablation, regardless of their site of origin (SOO) and the presence of structural heart disease.
Methods
This was a prospective, nonrandomized, multicenter study. The PM protocol was performed when <1 PVC/min was found. The \"target area\" was delimited by the 3 best matching points >94% correlation, and 3 radiofreqency (RF) applications were delivered.
Results
Of 185 patients, 105 (57%) underwent activation mapping, 60 (32%) were PM-guided, and 20 (11%) were canceled due to absence of PVCs. Baseline QRS, PVC burden, and outflow tract origin were independent predictors of PM-guided ablation. A higher proportion of right ventricular outflow tract SOO in the PM group (52% vs 40%; P = .03) was observed. Mean target area was 0.6 ± 0.9 cm2. Mean 10-ms isochronal area in local activation time (LAT)-guided procedures was higher (1.7 ± 2.3 cm2; P <.001). Mean number of PM matching points acquired was 39 ± 21 (range 6-98). Mean mapping and RF times were similar in both groups. However, significantly shorter procedural (53 ± 24 vs 61 ± 26 minutes; P = .04) as well as RF times (111 ± 51 vs 149 ± 149 seconds; P = .05) were needed in the PM group using the proposed protocol. Global clinical success reached 87% for the PM group and 90% (P = .58) the for LAT mapping group.
Conclusion
When LAT mapping is precluded, application of a PM-guided ablation protocol directed to >94% matching correlation target area is a more efficient alternative with comparable clinical results.

Copyright © 2021. Published by Elsevier Inc.

Heart Rhythm: 29 Sep 2021; 18:1709-1716
Jáuregui B, Penela D, Fernández-Armenta J, Acosta J, ... Pedrote A, Berruezo A
Heart Rhythm: 29 Sep 2021; 18:1709-1716 | PMID: 34029733
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Impact:
Abstract

Catheter Ablation for Persistent Atrial Fibrillation: a Multicentre Randomised Trial of Pulmonary Vein Isolation (PVI) versus PVI with Posterior Left Atrial Wall Isolation (PWI) - the CAPLA Study: CAPLA: randomised trial for persistent AF.

Chieng D, Sugumar H, Ling LH, Segan L, ... Kalman JM, Kistler PM
Background
The success of pulmonary vein isolation (PVI) is reduced in persistent AF (PsAF) compared to paroxysmal AF. Adjunctive ablation strategies have failed to show consistent incremental benefit over PVI alone in randomised studies. The left atrial posterior wall is a potential source of non-PV triggers and atrial substrate which may promote the initiation and maintenance of PsAF. Adding posterior wall isolation (PWI) to PVI had shown conflicting outcomes, with earlier studies confounded by methodological limitations.
Objectives
To determine whether combining PWI with PVI significantly improves freedom from AF recurrence, compared to PVI alone, in patients with PsAF.
Methods
This is a multi-centre, prospective, international randomised clinical trial. 338 patients with symptomatic PsAF refractory to anti-arrhythmic therapy (AAD) will be randomised to either PVI alone or PVI with PWI in a 1:1 ratio. PVI involves wide antral circumferential pulmonary vein (PV) isolation, utilising contact force sensing ablation catheters. PWI involves the creation of a floor line connecting the inferior aspect of the PVs, and a roof line connecting the superior aspect of the PVs. Follow up is for a minimum of 12 months with rhythm monitoring via implantable cardiac device/ loop monitor, or frequent intermittent monitoring with an ECG device. The primary outcome is freedom from any documented atrial arrhythmia of > 30 seconds off AAD at 12 months, after a single ablation procedure.
Conclusion
This randomised study aims to determine the success and safety of adjunctive PWI to PVI in patients with persistent AF.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Am Heart J: 03 Oct 2021; epub ahead of print
Chieng D, Sugumar H, Ling LH, Segan L, ... Kalman JM, Kistler PM
Am Heart J: 03 Oct 2021; epub ahead of print | PMID: 34619143
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Impact:
Abstract

Catheter ablation of ventricular tachycardia in nonischemic cardiomyopathy with near-normal left ventricular ejection fraction.

Bennett RG, Campbell T, Kotake Y, Turnbull S, Kumar S
Background
Patients with idiopathic nonischemic cardiomyopathy (NICM) and near-normal left ventricular ejection fraction (LVEF) may develop ventricular tachycardia (VT).
Objective
The purpose of this study was to describe procedural characteristics and outcomes in patients requiring ablation for NICM-related VT with near-normal LVEF compared to impaired LVEF.
Methods
Over 8 years, 77 consecutive patients with NICM-related VT underwent catheter ablation. Of these patients, 47 had idiopathic NICM (20 near-normal LVEF, 27 impaired LVEF). Procedural characteristics and outcomes were compared.
Results
Mean age was 64 ± 12years, mean LVEF was 40% ± 14%, and 75% were male. In the near-normal LVEF group compared to the impaired LVEF group, LVEF was higher (54% ± 5% vs 30 ± 8%; P <.001), scar was predominantly located in the perivalvular left ventricle (LV) and basal septum (15/20 [75%]), was smaller in size [bipolar: 9.7 (6.2-32.4) cm2 vs 30.4 (21.1-37.6) cm2, P = .03; unipolar: 23.3 (6.6-39.9) cm2 vs 57.2 (42.2-74.9) cm2, P = .009], and required smaller areas of ablation [7.0 (5.9-14.2) cm2 vs 11.4 (8.5-16.7) cm2, P = .06]. Both groups experienced comparable procedure times, fluoroscopy doses, ablation times, VT cycle lengths, and acute success rates. After final ablation, VA-free survival was comparable between both groups (65% vs 63%; P = .63) at 12 months.
Conclusion
Idiopathic NICM-related VT with near-normal LVEF was associated with discrete areas of arrhythmogenic, predominantly intramural, scar in the perivalvular LV and basal septum. Despite smaller scar, patients required similar ablation amounts and experienced comparable long-term outcomes compared to patients with idiopathic NICM-related VT and impaired LVEF. These findings underscore the \"three-dimensionality\" of substrate, whereby the intramural basal septum forms the third dimension and impacts ablation outcomes.

Crown Copyright © 2021. Published by Elsevier Inc. All rights reserved.

Heart Rhythm: 28 Sep 2021; epub ahead of print
Bennett RG, Campbell T, Kotake Y, Turnbull S, Kumar S
Heart Rhythm: 28 Sep 2021; epub ahead of print | PMID: 34597769
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Impact:
Abstract

Global approaches to cardiogenetic evaluation after sudden cardiac death in the young: A survey among health care professionals.

van den Heuvel LM, Do J, Yeates L, MacLeod H, ... van Tintelen JP, Ingles J
Background
Thorough investigation of sudden cardiac death (SCD) in those aged 1-40 years commonly reveals a heritable cause, yet access to postmortem genetic testing is variable.
Objective
The purpose of this study was to explore practices of postmortem genetic testing and attitudes of health care professionals worldwide.
Methods
A survey was administered among health care professionals recruited through professional associations, social media, and networks of researchers. Topics included practices around postmortem genetic testing, level of confidence in health care professionals\' ability, and attitudes toward postmortem genetic testing practices.
Results
There were 112 respondents, with 93% from North America, Europe, and Australia/New Zealand, and 7% from South America, Asia and Africa. Only 30% reported autopsy as mandatory, and overall practices were largely case by case and not standardized. North American respondents (87%) more often perceived practices as ineffective compared to those from Europe (58%) and Australia/New Zealand (48%; P = .002). Where a heritable cause is suspected, 69% considered postmortem genetic testing and 61% offered genetic counseling to surviving family members. Financial resources varied widely. Half of participants believed practices in their countries perpetuated health inequalities.
Conclusion
Postmortem genetic testing is not consistently available in the investigation of young SCD despite being a recommendation in international guidelines. Access to postmortem genetic testing, which is critical in ascertaining a cause of death in many cases, must be guided by well-resourced, multidisciplinary teams.

Copyright © 2021 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Heart Rhythm: 29 Sep 2021; 18:1637-1644
van den Heuvel LM, Do J, Yeates L, MacLeod H, ... van Tintelen JP, Ingles J
Heart Rhythm: 29 Sep 2021; 18:1637-1644 | PMID: 33781984
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Impact:
Abstract

Low-energy single-pulse surface stimulation defibrillates large mammalian ventricles.

Moreno A, Walton RD, Bernus O, Vigmond EJ, Bayer JD
Background
Strong electric shocks are the gold-standard for ventricular defibrillation, but are associated with pain and tissue damage. We hypothesize that targeting the excitable gap (EG) of reentry with low-energy surface stimulation is a less damaging and painless alternative for ventricular defibrillation.
Objective
Determine the conditions under which low-energy surface stimulation defibrillates large mammalian ventricles.
Methods
Low-energy surface stimulation was delivered with five 7 cm long electrodes placed 1-2 cm apart on the endocardial and epicardial surfaces of perfused pig left ventricle (LV). Rapid pacing (>4Hz) was used to induce reentry from a single electrode. A 2 ms defibrillation pulse ≤0.5A was delivered from all electrodes with a varied time delay from the end of the induction protocol (0.1-5 sec). Optical mapping was performed and arrhythmia dynamics analyzed. For mechanistic insight, simulations of the VF induction and defibrillation protocols were performed in-silico with an LV model emulating the experimental conditions, and electrodes placed 0.25-2 cm apart.
Results
In living LV, reentry was induced with varying complexity and dominant frequencies ranging between 3.5 to 6.2 Hz over 8 sec post-initiation. Low-energy defibrillation was achieved with energy <60 mJ and electrode separations up to 2 cm for less complex arrhythmia. In simulations, defibrillation consistently occurred when stimulation captured >75% of the EG, which blocked reentry <2.9 mm in front of the leading reentrant wavefront.
Conclusions
Defibrillation with low-energy single-pulse surface stimulation is feasible with energies below the human pain threshold (100 mJ). Optimal defibrillation occurs when arrhythmia complexity is minimal and electrodes capture >75% of the EG.

Copyright © 2021. Published by Elsevier Inc.

Heart Rhythm: 10 Oct 2021; epub ahead of print
Moreno A, Walton RD, Bernus O, Vigmond EJ, Bayer JD
Heart Rhythm: 10 Oct 2021; epub ahead of print | PMID: 34648972
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Impact:
Abstract

Sinus Rhythm QRS Amplitude and Fractionation in Patients with Non-Ischemic Cardiomyopathy to Identify Ventricular Tachycardia Substrate and Location.

Arceluz MR, Liuba I, Tschabrunn CM, Frankel DS, ... Zado ES, Marchlinski FE
Background
Ventricular tachycardia (VT) substrate in left ventricular (LV) nonischemic cardiomyopathy (NICM) consists of fibrosis with surviving myocardium.
Objective
To determine if, in patients with LV NICM and sustained VT, reduced QRS amplitude and QRSf during sinus rhythm can identify the presence and location of abnormal S-NICM and/or FW-NICM VT substrate.
Methods
We compared patients with NICM and VT (Group 1) with electroanatomic mapping septal (S-NICM, n=21) or free wall (FW-NICM, n=20) VT substrate to a 38 patient reference cohort (Group 2) with cardiac MRI (cMRI) and NICM but no VT referred for primary prevention ICD, 26 (68.4%) with late gadolinium enhancement (LGE).
Results
Group 1 had lower QRS amplitude in leads II (0.60±0.22 vs 0.86±0.35, p<0.001), aVR (0.60±0.24 vs 0.75±0.31, p=0.002), aVF (0.48±0.20 vs 0.70±0.28, p<0.001) and V2 (1.09±0.52 vs 1.38±0.55, p=0.001) than Group 2. A QRS <0.55 mV in lead aVF identified VT and accompanying substrate with sensitivity of 70% and specificity of 71%. Most Group 1 and Group 2 patients had 12-lead ECG QRSf in ≥2 contiguous leads (78% vs 63.2%, p=0.14). The sensitivity and specificity for ≥2 QRSf leads identifying respective regional electroantomic or cMRI abnormalities were 76% and 50% for inferior, 44% and 87% for lateral, 21% and 89% for anterior leads.
Conclusions
In LV NICM, low frontal plane QRS (< .55mV in avF) is associated with VT substrate. Although multi-lead QRS fractionation is associated with the presence and location of VT substrate, it is frequently identified in patients without VT with cMRI abnormalities.

Copyright © 2021. Published by Elsevier Inc.

Heart Rhythm: 29 Sep 2021; epub ahead of print
Arceluz MR, Liuba I, Tschabrunn CM, Frankel DS, ... Zado ES, Marchlinski FE
Heart Rhythm: 29 Sep 2021; epub ahead of print | PMID: 34601127
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Abstract

Identifying an Appropriate Endpoint for Cryoablation in Children with Atrioventricular Nodal Reentry Tachycardia: Is Residual Slow Pathway Conduction Associated with Recurrence?

Zook N, DeBruler K, Ceresnak S, Motonaga K, ... Dubin A, Chubb H
Background
Cryoablation is increasingly used to treat atrioventricular nodal reentry tachycardia (AVNRT) due to its safety profile. However, cryoablation may have higher recurrence than radiofrequency ablation (RFA) and the optimal procedural endpoint remains undefined.
Objective
The purpose of this study was to identify the association of cryoablation procedural endpoints with post-procedural AVNRT recurrence.
Methods
We performed a single-center, retrospective analysis of pediatric patients following successful first-time cryoablation for AVNRT between 1/1/2011 and 12/31/2019. Pre-ablation inducibility of AVNRT was recorded. Procedural endpoints, including slow pathway (SP) conduction (presence of jump or echo beats) with and without isoproterenol, were identified. Recurrence established from clinical notes and/or direct patient contact.
Results
Of 256 patients, 147(57%) were assessed on isoproterenol pre-cryoablation, and 171(47%) were assessed on isoproterenol post-cryoablation. Mean cryolesion time was 2586±1434 seconds. Following ablation, 104(41%) had some evidence of residual SP conduction. With median follow up time of 1.9[0.7-3.7] years, recurrence occurred in 14(5%) patients. Complete elimination of SP conduction (with and without isoproterenol) had a HR for recurrence of 1.26(95% CI 0.42-3.8, P=.68) on univariate analysis and 1.39(95% CI 0.36-5.4, P=.63) on multivariate analysis (including demographics, ablation time, 8mm cryocatheter and baseline inducibility).
Conclusion
The observed AVNRT recurrence rate after cryoablation was comparable to RFA. The presence of residual SP conduction was not associated with recurrence. This suggests that jump or single echo beat may be an acceptable endpoint in AVNRT cryoablation.

Copyright © 2021. Published by Elsevier Inc.

Heart Rhythm: 29 Sep 2021; epub ahead of print
Zook N, DeBruler K, Ceresnak S, Motonaga K, ... Dubin A, Chubb H
Heart Rhythm: 29 Sep 2021; epub ahead of print | PMID: 34601128
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Impact:
Abstract

Aorticorenal ganglion as a novel target for renal neuromodulation.

Hori Y, Temma T, Wooten C, Sobowale C, ... Peacock W, Ajijola OA
Background
Clinical trials for renal artery (RA) ablation have shown limited efficacy.
Objective
The purpose of this study was to investigate whether the aorticorenal ganglion (ARG) can be targeted for renal denervation.
Methods
Twenty-eight pigs were studied under isoflurane or alpha-chloralose to examine hemodynamic responses and catecholamine release in response to RA or ARG stimulation. To assess the efficacy of ARG ablation, we randomized 16 pigs to either sham, RA, or ARG ablation, followed by occlusion of the left anterior descending coronary artery (LAD). Hemodynamic responses, cardiac electrophysiological parameters, and arrhythmias/sudden cardiac death were assessed following LAD occlusion. Absent hemodynamic responses to stimulation confirmed ARG or RA ablation. In vivo stellate ganglion neural activity was recorded to assess cardiac sympathetic signaling. Cadaveric dissections were performed to localize the ARG in humans for comparison to swine.
Results
The ARG is a purely sympathetic ganglion with cholinergic inputs and pass-through sensory afferent fibers. Compared to RA stimulation, ARG stimulation yielded greater hemodynamic responses during alpha-chloralose anesthesia. However, neither site yielded significant responses under isoflurane. Radiofrequency ablation of the ARG eliminated responses to both RA and ARG stimulation, whereas RA ablation did not eliminate responses to ARG stimulation. Ablation of the ARG did not impact the kidneys or adrenal glands. Compared to control and RA ablation, ARG ablation was protective against ventricular arrhythmias and sudden death. Human and swine ARG are similarly located in the aorticorenal region.
Conclusion
Our findings indicate that the ARG may be a novel target for renal neuromodulation. Further studies are warranted to validate these findings.

Copyright © 2021 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Heart Rhythm: 29 Sep 2021; 18:1745-1757
Hori Y, Temma T, Wooten C, Sobowale C, ... Peacock W, Ajijola OA
Heart Rhythm: 29 Sep 2021; 18:1745-1757 | PMID: 34182169
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Impact:
Abstract

Nationwide burden of sudden cardiac death: A study of 54,028 deaths in Denmark.

Lynge TH, Risgaard B, Banner J, Nielsen JL, ... Winkel BG, Tfelt-Hansen J
Background
A large proportion of all deaths are sudden cardiac deaths (SCDs). Reliable estimates of nationwide incidence of SCD, however, are missing.
Objectives
The goals of this study were to estimate SCD burden across all age groups in Denmark and to compare it with the estimates of other common causes of death.
Methods
All deaths in Denmark (population of 5.5 million) in 2010 were manually reviewed case by case. Autopsy reports, death certificates, and information from nationwide health registries were systematically examined to identify all SCD cases in 2010. According to the level of detail of the available information, all deaths were categorized as either non-SCD, definite SCD, probable SCD, or possible SCD.
Results
There were 54,028 deaths in Denmark in 2010, of which 6867 (13%) were categorized as SCD (591 (9%) definite SCD, 1568 (23%) probable SCD, and 4708 (68%) possible SCD). The incidence rate of definite SCD was 11 (95% confidence interval 10-12) per 100,000 person-years. Including definite, probable, and possible SCD cases, the highest possible overall SCD incidence rate was 124 (95% confidence interval 121-127) per 100,000 person-years. Estimated SCD burden was similar to or greater than the estimates of all other common causes of death. Of all SCD cases, 49% were not diagnosed with cardiovascular disease before death.
Conclusion
SCD accounted for up to 13% of all deaths. Almost half of all SCD cases occurred in persons without a history of cardiovascular disease. Consequently, the optimization of risk stratification and prevention of SCD in the general population should be given high priority.

Copyright © 2021 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Heart Rhythm: 29 Sep 2021; 18:1657-1665
Lynge TH, Risgaard B, Banner J, Nielsen JL, ... Winkel BG, Tfelt-Hansen J
Heart Rhythm: 29 Sep 2021; 18:1657-1665 | PMID: 33965606
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Abstract

Postinfarct ventricular tachycardia substrate: Characterization and ablation of conduction channels using ripple mapping.

Katritsis G, Luther V, Jamil-Copley S, Koa-Wing M, ... Linton NWF, Kanagaratnam P
Background
Conduction channels have been demonstrated within the postinfarct scar and seem to be co-located with the isthmus of ventricular tachycardia (VT). Mapping the local scar potentials (SPs) that define the conduction channels is often hindered by large far-field electrograms generated by healthy myocardium.
Objective
The purpose of this study was to map conduction channel using ripple mapping to categorize SPs temporally and anatomically. We tested the hypothesis that ablation of early SPs would eliminate the latest SPs without direct ablation.
Methods
Ripple maps of postinfarct scar were collected using the PentaRay (Biosense Webster) during normal rhythm. Maps were reviewed in reverse, and clusters of SPs were color-coded on the geometry, by timing, into early, intermediate, late, and terminal. Ablation was delivered sequentially from clusters of early SPs, checking for loss of terminal SPs as the endpoint.
Results
The protocol was performed in 11 patients. Mean mapping time was 65 ± 23 minutes, and a mean 3050 ± 1839 points was collected. SP timing ranged from 98.1 ± 60.5 ms to 214.8 ± 89.8 ms post QRS peak. Earliest SPs were present at the border, occupying 16.4% of scar, whereas latest SPs occupied 4.8% at the opposing border or core. Analysis took 15 ± 10 minutes to locate channels and identify ablation targets. It was possible to eliminate latest SPs in all patients without direct ablation (mean ablation time 16.3 ± 11.1 minutes). No VT recurrence was recorded (mean follow-up 10.1 ± 7.4 months).
Conclusion
Conduction channels can be located using ripple mapping to analyze SPs. Ablation at channel entrances can eliminate the latest SPs and is associated with good medium-term results.

Copyright © 2021 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Heart Rhythm: 29 Sep 2021; 18:1682-1690
Katritsis G, Luther V, Jamil-Copley S, Koa-Wing M, ... Linton NWF, Kanagaratnam P
Heart Rhythm: 29 Sep 2021; 18:1682-1690 | PMID: 34004345
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Impact:
Abstract

Echocardiographic deformation imaging unmasks global and regional mechanical dysfunction in patients with idiopathic ventricular fibrillation: A multicenter case-control study.

Groeneveld SA, van der Ree MH, Taha K, de Bruin-Bon RHA, ... Postema PG, Hassink RJ
Background
Idiopathic ventricular fibrillation (IVF) is diagnosed in patients with sudden onset of ventricular fibrillation of unidentified origin. New diagnostic tools that can detect subtle abnormalities are needed to diagnose and treat patients with an underlying substrate.
Objective
The purpose of this study was to explore echocardiographic deformation characteristics in IVF patients.
Methods
Echocardiograms were analyzed with deformation imaging by 2-dimensional speckle tracking. Global and regional measurements of the left ventricle (LV) and right ventricle (RV) were performed. Regional LV deformation patterns were evaluated for the presence of postsystolic shortening. Regional RV deformation patterns were classified as type I (normal) or type II/III (abnormal).
Results
In total, 47 IVF patients (mean age 45 years; left ventricular ejection fraction [LVEF] 56%) and 47 healthy controls (mean age 41 years; LVEF 60%) were included. IVF patients showed more global deformation abnormalities as indicated by lower LV global longitudinal strain (18.5% ± 2.6% vs 21.6% ± 1.8%; P <.001) and higher LV mechanical dispersion (41 ± 12 ms vs 26 ± 6 ms; P <.001). In addition, IVF patients showed more regional LV postsystolic shortening compared to healthy controls (50% vs 11%; P <.001). Abnormal RV deformation patterns were observed in 16% of IVF patients and in none of the control subjects (P <.001).
Conclusion
We were able to show both regional and global echocardiographic deformation abnormalities in IVF patients. This study provides evidence that localized myocardial disease is present in a subset of IVF patients.

Copyright © 2021 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Heart Rhythm: 29 Sep 2021; 18:1666-1672
Groeneveld SA, van der Ree MH, Taha K, de Bruin-Bon RHA, ... Postema PG, Hassink RJ
Heart Rhythm: 29 Sep 2021; 18:1666-1672 | PMID: 34058391
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Impact:
Abstract

Trends in Implantable Cardioverter-Defibrillator Programming Practices and its Impact on Therapies: Insights from a North American Remote Monitoring Registry 2007 - 2018.

Bennett MT, Brown ML, Koehler J, Lexcen DR, Cheng A, Cheung JW
Background
Recent evidence has revealed the utility of prolonged arrhythmia detection duration and increased rate cutoff to reduce implantable cardioverter-defibrillator (ICD) therapies. Data on real-world trends in ICD programming and its impact on outcomes are limited.
Objective
Evaluate trends in ICD programming and its impact on ICD therapy using a large remote monitoring database.
Methods
A retrospective analysis of ICD patients implanted from 2007-2018 was conducted using the de-identified Medtronic CareLink Database. Data on ICD programming (number of intervals to detection (NID) and therapy rate cutoff) and delivered ICD therapies were collected.
Results
Among 210,810 patients, the proportion programmed to a rate cutoff ≥ 188 bpm increased from 41% to 49% and an NID of ≥ 30/40 increased from 17% to 67% from before May 2013 versus after February 2016. Programming to a rate cutoff ≥ 188 bpm, ventricular fibrillation (VF) NID ≥ 30/40 or combined rate cutoff ≥ 188 bpm and VF NID ≥30/40 were associated with reductions in ICD therapy. The largest reductions in ICD therapy occurred when the combination of rate cutoff ≥ 188 bpm and VF NID ≥ 30/40 was programmed (anti-tachycardia pacing (ATP): hazard ratio (HR): 0.35, confidence interval (CI): 0.34-0.36, p<0.001; shocks: HR: 0.67, CI: 0.65-0.69, p<0.001; and ATP/shocks: HR: 0.43, CI: 0.42-0.44, p<0.001).
Conclusions
Despite evidence supporting the use of prolonged detection duration and high rate cutoff, implementation of shock reduction programming strategies in real-world clinical practice has been modest. The use of evidence-based ICD programming is associated with reduced ICD shocks over long-term follow-up.

Copyright © 2021. Published by Elsevier Inc.

Heart Rhythm: 13 Oct 2021; epub ahead of print
Bennett MT, Brown ML, Koehler J, Lexcen DR, Cheng A, Cheung JW
Heart Rhythm: 13 Oct 2021; epub ahead of print | PMID: 34656774
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Impact:
Abstract

A governing equation for rotor and wavelet number in human clinical ventricular fibrillation: Implications for sudden cardiac death.

Dharmaprani D, Jenkins EV, Quah JX, Lahiri A, ... Nash MP, Ganesan AN
Background
Ventricular fibrillation (VF) is characterised by multiple wavelets and rotors. No equation to predict the number of rotors and wavelets observed during fibrillation has been validated in human VF.
Objective
We hypothesized a single equation derived from a Markov M/M/∞ birth-death process, could predict the number of rotors and wavelets occurring in human clinical VF.
Methods
Epicardial induced VF (256-electrodes) recordings obtained from patients undergoing cardiac surgery were studied (n=12 patients, n=62 epochs). Rate constants for phase singularity (PS, which occur at the pivot points of rotors) and wavefront (WF) formation and destruction were derived by fitting distributions to PS and WF inter-formation and lifetimes. These rate-constants were combined in an M/M/∞ governing equation to predict the number of PS and WF in VF episodes. Observed distributions were compared to those predicted by the M/M/∞ equation.
Results
The M/M/∞ equation accurately predicted average PS and WF number and population distribution, demonstrated in all epochs. Self-terminating episodes of VF were distinguished from VF episodes requiring termination by a trend towards slower PS destruction, and slower rates of PS formation, and a slower mixing rate of the VF process, indicated by larger values of the second-largest eigenvalue modulus (SLEM) of the M/M/∞ birth-death matrix. The longest-lasting PS (associated with rotors) had shorter inter-activation time intervals compared to shorter lasting PS lasting <150 ms (∼1 PS rotation in human VF).
Conclusions
The M/M/∞ equation explains the number of wavelets and rotors observed, supporting a paradigm of VF based on statistical fibrillatory dynamics.

Copyright © 2021. Published by Elsevier Inc.

Heart Rhythm: 14 Oct 2021; epub ahead of print
Dharmaprani D, Jenkins EV, Quah JX, Lahiri A, ... Nash MP, Ganesan AN
Heart Rhythm: 14 Oct 2021; epub ahead of print | PMID: 34662707
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Impact:
Abstract

Quality of Life Following Initial Treatment of Atrial Fibrillation with Cryoablation Versus Drug Therapy Initial Treatment with Cryoablation or Drug Therapy.

Wazni O, Dandamudi G, Sood N, Hoyt R, ... Nissen SE, STOP-AF First Trial Investigators
Background
The STOP AF First trial recently demonstrated that initial treatment with cryoballoon ablation (CBA) is safe and superior to antiarrhythmic drug (AAD) therapy for preventing atrial arrhythmia recurrence in patients with symptomatic atrial fibrillation (AF).
Objective
To evaluate the change in quality of life (QoL) and symptoms following first-line CBA versus AAD therapy.
Methods
Patients with symptomatic AF not previously receiving rhythm control therapy were randomized to AAD (class I or III) or CBA (Arctic Front Advance, Medtronic). QoL was evaluated at baseline, 6 and 12-months using the Atrial Fibrillation Effect on QualiTy-of-Life (AFEQT) and the European Quality of Life-5 Dimensions (EQ-5D) questionnaires. A review of AF-associated symptoms was conducted at baseline, 1, 3, 6 and 12-months.
Results
In total, 203 subjects received either CBA (n=104) or AAD therapy (n=99). Improvements in the AFEQT summary and subscale scores were significantly larger with CBA vs. AAD therapy at 6 and 12 months (all p<0.02). Clinically meaningful improvement (>5 points) in the AFEQT summary score from baseline to 12 months was observed in 96.0% of patients in the CBA arm vs. 72.2% of patients in the AAD arm (p<0.001). No significant between group differences were observed in the change in EQ-5D index or visual analogue scores. Overall, 54.4% of the CBA group vs. 29.7% of the AAD group reported no AF-specific symptom recurrence following a 90-day blanking period (p=0.0005).
Conclusions
First-line CBA vs. AAD therapy is associated with larger improvements in AF-specific QoL and a higher rate of symptom resolution.

Copyright © 2021. Published by Elsevier Inc.

Heart Rhythm: 15 Oct 2021; epub ahead of print
Wazni O, Dandamudi G, Sood N, Hoyt R, ... Nissen SE, STOP-AF First Trial Investigators
Heart Rhythm: 15 Oct 2021; epub ahead of print | PMID: 34666139
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Impact:
Abstract

Risk of Major Bleeding in Patients With Atrial Fibrillation Taking Dronedarone in Combination With a Direct Acting Oral Anticoagulant (From a U.S. Claims Database).

Gandhi SK, Reiffel JA, Boiron R, Wieloch M
Dronedarone may increase exposure and the risk of major bleeding when prescribed with a direct oral anticoagulant (DOAC). This retrospective cohort study examined the risk of the first occurrence of major bleeding (hospitalization or emergency room visit for gastrointestinal [GI] bleeding, intracranial hemorrhage [ICH], or bleeding at other sites) among new users of apixaban, dabigatran, and rivaroxaban in patients with AF ≥18 years (January 1, 2007 to September 30, 2017) from the United States Truven Health MarketScan claims, comparing concomitant users of dronedarone to DOAC alone users in patients with atrial fibrillation (AF). No increased risk of major bleeding was associated with use of dronedarone and apixaban (adjusted Hazard Ratio [aHR]: 0.69 [95% confidence interval [CI]: 0.40, 1.17], p = 0.16), a modestly increased risk of GI bleeding but not overall bleeding was associated with use of dronedarone and dabigatran (aHR bleeding: 1.18 [95% CI: 0.89, 1.56], p = 0.26; aHR GI bleeding: 1.40 [95% CI: 1.01, 1.93]; p = 0.04) and an increased risk of overall bleeding, driven by GI bleeding, was associated with use of dronedarone and rivaroxaban (aHR bleeding: 1.31 [95% CI: 1.01, 1.69]; p = 0.04; aHR GI bleeding: 1.39 [95% CI: 0.98, 1.95]; p = 0.06), compared to each DOAC respectively. There was no increased risk of ICH associated with combined use of dronedarone and any DOAC. Prospective analyses, preferably randomized controlled studies, are needed to further explore the risk of major bleeding with concomitant use of DOACs and CYP3A4/P-gp inhibitors such as dronedarone.

Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

Am J Cardiol: 14 Nov 2021; 159:79-86
Gandhi SK, Reiffel JA, Boiron R, Wieloch M
Am J Cardiol: 14 Nov 2021; 159:79-86 | PMID: 34656316
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Impact:
Abstract

Electrical cardioversion of atrial fibrillation and the risk of brady-arrhythmic events: Rasmussen et al: Electrical cardioversion and bradycardia.

Rasmussen PV, Blanche P, Dalgaard F, Gislason GH, ... Pallisgaard JL, Hansen ML
Background
Electrical cardioversion (ECV) is a common procedure for terminating atrial fibrillation (AF). ECV is associated with brady-arrhythmic events, however, the age-specific risks of clinically significant brady-arrhythmic events are unknown.
Methods
Using Danish nationwide registers, we identified patients with AF at their first non-emergent ECV between 2005 and 2018 and estimated their 30-day risk of brady-arrhythmic events. Moreover, factors associated with increased risks of brady-arrhythmias were identified. Absolute risks were estimated using logistic regression models fitted with natural splines as well as standardization (G-formula).
Results
We identified 20,725 eligible patients with a median age of 66 years (IQR 60-72) and most males (73%). The 30-day risks of brady-arrhythmic events after ECV were highly dependent on age with estimated risks ranging from 0.5 % (95% CI 0.2-1.7) and 1.2 % (95% CI 0.99-1.5) to 2.7 % (95% CI 2.1-3.3), and 5.1 % (95% 2.6-9.7) in patients aged 40, 65, 80, and 90 years, respectively. Factors associated with brady-arrhythmias were generally related to cardiovascular disease (e.g. ischemic heart disease, heart failure, valvular AF) or a history of syncope. We found no indications that pre-treatment with AADs conferred increased risks of brady-arrhythmic events (standardized absolute risk difference -0.25 % [95% CI -0.67 - 0.17]).
Conclusions
ECV conferred clinically relevant 30-day risks of brady-arrhythmic events, especially in older patients. AAD treatment was not found to increase the risk of brady-arrhythmias. Given the widespread use of ECV, these data should provide insights regarding the potential risks of brady-arrhythmic events.

Copyright © 2021. Published by Elsevier Inc.

Am Heart J: 15 Oct 2021; epub ahead of print
Rasmussen PV, Blanche P, Dalgaard F, Gislason GH, ... Pallisgaard JL, Hansen ML
Am Heart J: 15 Oct 2021; epub ahead of print | PMID: 34666012
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Impact:
Abstract

Fascicular heart blocks and risk of adverse cardiovascular outcomes: results from a large primary care population.

Nyholm BC, Ghouse J, Ji-Young Lee C, Rasmussen PV, ... Nielsen JB, Skov MW
Background
Fascicular heart blocks can progress to complete heart blocks, but this risk has not been evaluated in a large general population.
Objective
To investigate the association between various types of fascicular blocks diagnosed by electrocardiogram (ECG) readings and the risk of incident higher degree atrioventricular block (AVB), syncope, pacemaker implantation and death.
Methods
We studied primary care patients referred for ECG recording between 2001 and 2015. Cox regression models were used to estimate hazard ratios (HR) as well as absolute risks of cardiovascular outcomes.
Results
Of 358,958 primary care patients (median age 54 years, 55% women), 13,636 (3.8%) had any type of fascicular block. Patients were followed up to 15.9 years. We found increasing hazard ratios of incident syncope, pacemaker implantation, and 3rd degree AVB with increasing complexity of fascicular block. Compared with no block, isolated left anterior fascicular block (LAFB) was associated with 0-2% increased 10-year risk of developing 3rd degree AVB (hazard ratio [HR] 1.6, 95% confidence interval [CI] 1.25-2.05), whereas right bundle branch block combined with LAFB and 1st degree AVB was associated with up to 23% increased 10-year risk (HR 11.0, 95% CI 7.7-15.7), depending on age- and sex group. Except for left posterior fascicular block (HR 2.09, 95% CI 1.87-2.32), we did not find any relevant associations between fascicular block and death.
Conclusion
We found that higher degrees of fascicular blocks were associated with increasing risk of syncope, pacemaker implantation, and complete heart block, but the association with death was negligible.

Copyright © 2021. Published by Elsevier Inc.

Heart Rhythm: 17 Oct 2021; epub ahead of print
Nyholm BC, Ghouse J, Ji-Young Lee C, Rasmussen PV, ... Nielsen JB, Skov MW
Heart Rhythm: 17 Oct 2021; epub ahead of print | PMID: 34673253
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Impact:
Abstract

Rotors anchored by refractory islands drive Torsades de Pointes in an experimental model of electrical storm.

Yamazaki M, Tomii N, Tsuneyama K, Takanari H, ... Nattel S, Tsuji Y
Background
Electrical storm (ES) is a life-threatening emergency in patients at high risk of ventricular tachycardia/fibrillation (VT/VF), but the pathophysiology and molecular basis are poorly understood.
Objective
To explore the electrophysiological substrate for experimental ES.
Methods
A model was created by inducing chronic complete atrioventricular-block in defibrillator-implanted rabbits, which recapitulates QT-prolongation, Torsades-des-Pointes (TdP) and VF-episodes.
Results
Optical mapping revealed island-like regions with action potential duration (APD) prolongation in the left ventricle (LV), leading to increased spatial APD-dispersion, in rabbits with ES (defined as ≥3 VF-episodes/24-h). The maximum APD and its dispersion correlated with the total number of VF-episodes in-vivo. TdP was initiated by an ectopic beat that failed to enter the island and formed a reentrant wave, and perpetuated by rotors whose centers swirled in the periphery of the island. Epinephrine exacerbated the island by prolonging APD and enhancing APD-dispersion, which was less evident after late Na+-current (INa-L) blockade with 10 μM ranolazine. Non-sustained VT in a non-ES rabbit heart with homogeneous APD prolongation resulted from multiple foci with an electrocardiographic morphology different from TdP driven by drifting rotors in ES-rabbit hearts. The neuronal Na+-channel subunit NaV1.8 was upregulated in ES-rabbit LV-tissues and expressed within myocardium corresponding to the island location in optically mapped ES-rabbit hearts. The NaV1.8-blocker A-803467 (10 mg/kg, i.v.) attenuated QT-prolongation and suppressed epinephrine-evoked TdP.
Conclusion
A tissue-island with enhanced refractoriness contributes to the generation of drifting rotors that underlies ES in this model. NaV1.8-mediated INa-L merits further investigation as a contributor to the substrate for ES.

Copyright © 2021. Published by Elsevier Inc.

Heart Rhythm: 18 Oct 2021; epub ahead of print
Yamazaki M, Tomii N, Tsuneyama K, Takanari H, ... Nattel S, Tsuji Y
Heart Rhythm: 18 Oct 2021; epub ahead of print | PMID: 34678525
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Impact:
Abstract

Design and Rationale of a Phase 2 Study of NeurOtoxin (Botulinum Toxin Type A) for the PreVention of Post-Operative Atrial Fibrillation - The NOVA Study.

Piccini JP, Ahlsson A, Dorian P, Gillinov MA, ... Ferguson WG, Benussi S
Background
Post-operative AF (POAF) is the most common complication following cardiac surgery, occurring in 30% to 60% of patients undergoing bypass and/or valve surgery. POAF is associated with longer intensive care unit/hospital stays, increased healthcare utilization, and increased morbidity and mortality. Injection of botulinum toxin type A into the epicardial fat pads resulted in reduction of AF in animal models, and in 2 clinical studies of cardiac surgery patients, without new safety observations.
Methods
The objective of NOVA is to assess the use of AGN-151607 (botulinum toxin type A) for prevention of POAF in cardiac surgery patients. This randomized, multi-site, placebo-controlled trial will study one-time injections of AGN-151607 125 U (25 U / fat pad) and 250 U (50 U / fat pad) or placebo during cardiac surgery in ∼330 participants. Primary endpoint: % of patients with continuous AF ≥ 30 s. Secondary endpoints include several measures of AF frequency, duration, and burden. Additional endpoints include clinically important tachycardia during AF, time to AF termination, and healthcare utilization. Primary and secondary efficacy endpoints will be assessed using continuous ECG monitoring for 30 days following surgery. All patients will be followed for up to 1 year for safety.
Conclusion
The NOVA Study will test the hypothesis that injections of AGN-151607 will reduce the incidence of POAF and associated resource utilization. If demonstrated to be safe and effective, the availability of a one-time therapy for the prevention of POAF would represent an important treatment option for patients undergoing cardiac surgery.

Copyright © 2021. Published by Elsevier Inc.

Am Heart J: 19 Oct 2021; epub ahead of print
Piccini JP, Ahlsson A, Dorian P, Gillinov MA, ... Ferguson WG, Benussi S
Am Heart J: 19 Oct 2021; epub ahead of print | PMID: 34687654
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Impact:
Abstract

Predictors of Perforation During Lead Extraction; Results of the Canadian Lead ExtrAction Risk (CLEAR) Study.

Bashir J, Lee AJ, Philippon F, Mondesert B, ... Tyers GFO, Andrade J
Background
Transvenous lead extraction can have serious adverse events such as cardiac or vascular perforation. Risk factors have not been well characterized.
Objective
To identify factors associated with perforation and death, and characterize lead extraction in a large contemporary population.
Methods
We performed a retrospective multi-center study examining patients undergoing lead extraction at 8 Canadian institutions from 1996 through 2016. Demographic and clinical data were used to identify variables associated with perforation and mortality using logistic regression modelling.
Results
2,325 consecutive patients (61.9 ±16.5 years) underwent extraction of 4,527 leads. Perforation rate was 2.7% (63/2,325) and 30-day mortality was 1.6% with mortality of 0.4% due to perforation (38/2,325; 10/2325). Variables associated with perforation included no previous cardiac surgery (Odds ratio [OR] 3.33, 95% confidence interval [CI] 1.54-7.19, p=0.002), female sex (OR 3.27, 95% CI 1.91-5.60, p<0.001), left ventricular ejection fraction > 40% (OR 2.81, 95% CI 1.28-6.14, p=0.010), lead age >8 years (OR 2.64, 95% CI 1.52-4.60, p<0.001), ≥ 2 leads extracted (OR 2.49, 95% CI 1.23-5.04, p=0.011), and diabetes (OR 2.12, 95% CI 1.16-3.86, p=0.014). Variables associated with death included infection as indication for extraction (OR 3.85, 95% CI 1.38-10.73, p=0.010), anemia (OR 3.14, 95% CI 1.38-6.61, p=0.003) and patient age (OR 1.04, 95% CI 1.01-1.07, p=0.012).
Conclusion
Risk factors associated with perforation in lead extraction include no history of cardiac surgery, female sex, preserved left ventricular ejection fraction, lead age > 8 years, ≥ 2 leads extracted, and diabetes.

Copyright © 2021. Published by Elsevier Inc.

Heart Rhythm: 21 Oct 2021; epub ahead of print
Bashir J, Lee AJ, Philippon F, Mondesert B, ... Tyers GFO, Andrade J
Heart Rhythm: 21 Oct 2021; epub ahead of print | PMID: 34695576
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Impact:
Abstract

The effect of left atrial appendage closure on heart failure biomarkers: A PRAGUE-17 trial subanalysis.

Herman D, Osmancik P, Neuzil P, Hala P, ... Reddy VY, PRAGUE-17 Trial Investigators
Introduction
The randomized PRAGUE-17 trial demonstrated noninferiority of left atrial appendage closure (LAAC) to non-vitamin K anticoagulants (NOACs) for the prevention of major cardiovascular or cerebrovascular events. However, the left atrial appendage is an important source of natriuretic peptides and plays a role in left atrial reservoir function. Changes of heart failure (HF) biomarkers after LAAC compared to NOAC has not been studied. The aim of the study was to compare the changes in concentrations of HF biomarkers between LAAC and NOAC patients.
Methods
Of 402 patients randomized in the PRAGUE-17 trial, biomarkers were analyzed in 144 patients (73 in the NOAC and 71 in the LAAC group). Both groups had similar baseline characteristics. Serum concentration of NT-proBNP, NT-proANP, Galectin-3, and GDF-15 were measured at baseline (before the procedure in the LAAC group), at the 6-month (and at 24-month for NT-proBNP) follow-up timepoint.
Results
There were no significant differences in baseline, 6 month, and delta (δ = baseline - 6 month) concentrations of NT-proANP between the groups (NOAC: baseline 2.6 [0.5; 4.9], 6-month 3.1 [1.8; 4.8], p = .068; LAAC: baseline 3.3 [1.1; 4.6], 6-month 2.6 [0.9; 5.3], p = .51; p value for δ in concentrations between groups = 0.42). Similarly, there were no significant differences in baseline, 6, 24 months, and delta concentrations of NT-proBNP between the groups (NOAC: baseline 461.0 [113.5; 1342.0], 6 month 440.0 [120.5; 1291.5], 24 month 798 [274; 2236], p = .39; LAAC: baseline 421.0 [100.0; 1320.0], 6 month 601.0 [145.0; 1230.0], 24 month 855 [410; 1367], p = .28; p value for δ in concentrations between groups = 0.73 at 6 months, and 0.58 at 24 months). Finally, no significant differences were present in baseline, 6 month, and δ concentrations of Galectin-3 and GDF-15 between the two groups.
Conclusion
LAAC did not significantly influence the levels of HF biomarkers 6 months after the procedure.

© 2021 Wiley Periodicals LLC.

J Cardiovasc Electrophysiol: 29 Sep 2021; 32:2645-2654
Herman D, Osmancik P, Neuzil P, Hala P, ... Reddy VY, PRAGUE-17 Trial Investigators
J Cardiovasc Electrophysiol: 29 Sep 2021; 32:2645-2654 | PMID: 34402135
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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: 08 Oct 2021; 23:1586-1595
Varma N, Auricchio A, Connolly AT, Boehmer J, ... Nabutovsky Y, Gold M
Europace: 08 Oct 2021; 23:1586-1595 | PMID: 34198334
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Abstract

Severity of congenital long QT syndrome disease manifestation and risk of depression, anxiety, and mortality: a nationwide study.

Krøll J, Jensen HK, Jespersen C, Kanters JK, ... Tfelt-Hansen J, Weeke PE
Aims
We examined if a congenital long QT syndrome (cLQTS) diagnosis and severity of cLQTS disease manifestation was associated with increased risk of depression, anxiety, and all-cause mortality.
Methods and results
All patients with known cLQTS in Denmark were identified using nationwide registries and specialized inherited cardiac disease clinics (1994-2016) and followed for up to 3 years after their cLQTS diagnosis. Risk factors for depression, anxiety, and all-cause mortality were determined using multivariable Cox proportional-hazards regression. An age- and sex-matched control population was identified (matching 1:4). Overall, 589 patients with cLQTS were identified of which 119/589 (20.2%) developed depression or anxiety during follow-up compared with 302/2356 (12.8%) from the control population (P < 0.001). Severity of cLQTS disease manifestation was identified for 324/589 (55%) of patients with cLQTS; 162 were asymptomatic, 119 had ventricular tachycardia (VT)/syncope, and 43 had aborted sudden cardiac death (aSCD). In multivariable models, patients with aSCD, VT/syncope, or unspecified cLQTS disease manifestation had a higher risk of developing depression or anxiety compared with the control population (hazard ratio [HR]=2.4, 95% confidence interval [CI]: 1.1-5.1; HR = 1.9, 95% CI: 1.2-3.0; HR = 1.6, 95% CI: 1.1-2.3, respectively). Asymptomatic patients had similar risk of developing depression or anxiety as the control population (HR = 1.2, 95% CI: 0.8-1.9). During follow-up, 10/589 (1.7%) patients with cLQTS died compared with 27/2356 (1.1%) from the control population (P = 0.5). Furthermore, 4/10 who died had developed depression or anxiety.
Conclusion
A severe cLQTS disease manifestation was associated with a greater risk of depression or anxiety. All-cause mortality for patients with cLQTS was low.

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

Europace: 14 Oct 2021; epub ahead of print
Krøll J, Jensen HK, Jespersen C, Kanters JK, ... Tfelt-Hansen J, Weeke PE
Europace: 14 Oct 2021; epub ahead of print | PMID: 34652436
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Impact:
Abstract

Association of Left Atrial Metrics with Atrial Fibrillation Rehospitalization and Adverse Cardiovascular Outcomes in Patients with Nonvalvular Atrial Fibrillation following Index Hospitalization.

Bhat A, Gan GCH, Chen HHL, Khanna S, ... MacIntyre CR, Tan TC
Background
Atrial fibrillation (AF) is the most common arrhythmia encountered in clinical practice, with significant clinical and economic burdens, largely driven by adverse cardiovascular outcomes and AF-related hospitalization. Left atrial (LA) parameters have been shown to have prognostic value in cardiovascular disease states. We sought to evaluate the prognostic value of measures of LA size and function, as measured through LA volume index and LA emptying fraction (LAEF), respectively, for AF rehospitalization and long-term adverse outcomes in patients with nonvalvular AF following index hospitalization.
Methods
In this retrospective study, 594 consecutive patients (mean age, 67.8 ± 13.6 years, 53% men) admitted to a tertiary referral center with nonvalvular AF were assessed. Patients who underwent transthoracic echocardiography during their index admission and had complete follow-up data were included and followed for a mean period of 33.18 ± 21.27 months for the primary outcome of AF rehospitalization. The secondary outcome was a composite of all-cause death and major adverse cardiovascular events.
Results
The primary outcome occurred in 250 (42%) patients, and the secondary outcome occurred in 219 (37%) patients. On multivariable regression analysis, LAEF had an independent association with AF rehospitalization (hazard ratio [HR] = 0.967; 95% CI, 0.953-0.982; P < .01), and time-dependent receiver operating characteristic curves demonstrated LAEF to have strong diagnostic accuracy in predicting early and intermediate AF rehospitalization. Both LA volume index (HR = 1.014; 95% CI, 1.003-1.026; P = .01) and LAEF (HR = 0.982; 95% CI, 0.970-0.993; P < .01) were associated with all-cause death and major adverse cardiovascular events.
Conclusions
Adverse LA remodeling, as reflected through LA enlargement and reduced LA mechanical function, is associated with AF rehospitalization and long-term adverse cardiovascular outcomes in hospitalized patients with nonvalvular AF.

Copyright © 2021 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.

J Am Soc Echocardiogr: 29 Sep 2021; 34:1046-1055.e3
Bhat A, Gan GCH, Chen HHL, Khanna S, ... MacIntyre CR, Tan TC
J Am Soc Echocardiogr: 29 Sep 2021; 34:1046-1055.e3 | PMID: 34245827
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Impact:
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: 08 Oct 2021; 23:1511-1527
Stevens D, Harrison SL, Kolamunnage-Dona R, Lip GYH, Lane DA
Europace: 08 Oct 2021; 23:1511-1527 | PMID: 34125202
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Impact:
Abstract

The association between late-phase early recurrence within the blanking period after atrial fibrillation catheter ablation and long-term recurrence: Insights from a large-scale multicenter study.

Onishi N, Kaitani K, Nakagawa Y, Inoue K, ... Shizuta S, EAST-AF Investigators
Background
The relationship between the timing of the first early recurrence and late recurrence after a single catheter ablation procedure for atrial fibrillation is controversial.
Methods
The Efficacy of Short-Term Use of Antiarrhythmic Drugs After Catheter Ablation for Atrial Fibrillation trial followed 2038 patients who underwent radiofrequency catheter ablation for atrial fibrillation.
Results
Of the patients, 907 (45%) had early recurrences within 90 days after the initial ablation. We divided these patients into two groups according to the timing of the first early recurrence episode, namely the ER1 group (early recurrence during the early phase; 0-30 days, n = 814) and ER2 group (early recurrence during the late phase; 31-90 days, n = 93). Three years after ablation, patients with early recurrences had a significantly lower event-free rate from late recurrences after a 90-day blanking period than patients without early recurrences (36.2% and 74.2%, respectively; log-rank, P < 0.0001). Three years after ablation, the event-free rate was significantly higher in the ER1 than the ER2 group (38.3% and 17.1%, respectively; log-rank, P < 0.0001). Moreover, the event-free rate at 3 years in the ER2 group was extremely low (5.6%) in patient with non-paroxysmal atrial fibrillation.
Conclusion
Early recurrences were strongly associated with late recurrences, especially in patients with the first recurrence episode at >1 month within the blanking period after a single ablation procedure. Therefore, these patients should undergo close observation during follow-up, when they had especially with non-paroxysmal atrial fibrillation.

Copyright © 2021. Published by Elsevier B.V.

Int J Cardiol: 14 Oct 2021; 341:39-45
Onishi N, Kaitani K, Nakagawa Y, Inoue K, ... Shizuta S, EAST-AF Investigators
Int J Cardiol: 14 Oct 2021; 341:39-45 | PMID: 34343532
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Impact:
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 1.35, 95% CI 1.15-1.59), 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: 08 Oct 2021; 23:1528-1538
Noubiap JJ, Feteh VF, Middeldorp ME, Fitzgerald JL, ... Lau DH, Sanders P
Europace: 08 Oct 2021; 23:1528-1538 | PMID: 34279604
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Impact:
Abstract

Cryofreezing for slow-pathway modification in patients with slow-fast AVNRT: Efficacy, safety, and electroanatomical relation between sites of transient AV block and sites of successful cryoablation.

Fukuda R, Nakahara S, Wakamatsu Y, Hori Y, ... Ishikawa T, Taguchi I
Introduction
Cryoablation has emerged as an alternative to radiofrequency ablation for treating atrioventricular nodal reentrant tachycardia (AVNRT). The aim of this prospective study was to evaluate the efficacy and safety of cryoapplication at sites within the mid/high septal region of Koch\'s triangle and the relation between sites of transient AV block (AVB) and sites of successful cryoablation.
Methods and results
Included were 45 consecutive patients undergoing slow-fast AVNRT cryoablation. Initial delivery of cryoenergy was to the mid-septal to high septal region of Koch\'s triangle. Transient AVB occurred during cryoenergy delivery in 62% (28/45) of patients. Median distance between sites at which cryofreezing successfully eliminated slow pathway conduction and sites of AVB was 4.0 (3.25-5.0) mm. Sites of successful cryoablation tended to be to the left and inferior to the AVB sites. The atrial/ventricular electrogram ratio was significantly lower at sites of successful cryoablation than at AVB sites (0.25 [0.17-0.56] vs. 0.80 [0.36-1.25], p < .001). Delayed discrete or fractionated atrial electrograms were recorded more frequently at sites of successful cryoablation than at AVB sites (78% vs. 20%, p < .001). No persistent AV conduction disturbance occurred, and 96% (43/45) of patients showed absence of recurrence at a median follow-up time of 25.0 months.
Conclusion
Cryoablation of slow-fast AVNRT and targeting the mid/high septal region of Koch\'s triangle was highly successful. AVB frequently emerged near the site at which the slow pathway was eliminated but always resolved by regulating the energy delivery under careful monitoring, and it may be distinguishable by its local electrogram features.

© 2021 Wiley Periodicals LLC.

J Cardiovasc Electrophysiol: 27 Sep 2021; epub ahead of print
Fukuda R, Nakahara S, Wakamatsu Y, Hori Y, ... Ishikawa T, Taguchi I
J Cardiovasc Electrophysiol: 27 Sep 2021; epub ahead of print | PMID: 34582058
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Impact:
Abstract

High-risk features and predictors of unexplained syncope in the young SCD-SOS cohort.

Carrington M, Pais J, Brás D, Creta A, ... Gonçalves L, Providência R
Introduction
The Sudden Cardiac Death-Screening of Risk FactOrS survey included a 12-lead electrocardiogram (ECG) plus a digital-based questionnaire and aimed to screen for warning signs of diseases that may course with sudden cardiac death in children and young adults. We aimed to estimate the prevalence of unexplained syncope (US) and characterize its high-risk features and predictors in this cohort.
Methods and results
We determined the most probable etiology of transient loss of consciousness (TLOC) episodes based on clinical criteria. US was an exclusion diagnosis and we analyzed its potential clinical and ECG predictors. Among 11 878 individuals, with a mean age of 21 ± 6 (range 6-40) years old, the cumulative incidence of TLOC was 26.5%, 76.2% corresponding to females. Reflex syncope was present in 66.4%, orthostatic hypotension in 8.2%, and 14.8% of the individuals had US. Unexplained syncope was independently associated with age < 18 years old (odds ratio [OR] 1.695; 95% confidence interval [CI] 1.26-2.29, p = .001), male gender (OR 1.642; 95% CI 1.22-2.22, p = .001), participation in competitive sports (OR 1.644; 95% CI 1.01-2.66, p = .043), syncope during exertion and/or palpitations preceding syncope (OR 2.556; 95% CI 1.92-3.40, p < .001), syncope after exertion (OR 2.662; 95% CI 1.73-4.10, p < .001), fever context (OR 9.606; 95% CI 4.13-22.34, p < .001), isolated previous syncopal episode (OR 2.780; 95% CI 0.2.06-3.75, p < .001), and history of palpitations requiring medical care (OR 1.945; 95% CI 1.14-3.31, p = .014). We found no ECG predictors of US in this population.
Conclusions
The cumulative incidence of TLOC in children and young adults is high and remains unexplained in an important proportion of individuals. We identified eight clinical characteristics that may be useful for the risk stratification of individuals evaluated in a nonacute setting.

© 2021 Wiley Periodicals LLC.

J Cardiovasc Electrophysiol: 29 Sep 2021; 32:2737-2745
Carrington M, Pais J, Brás D, Creta A, ... Gonçalves L, Providência R
J Cardiovasc Electrophysiol: 29 Sep 2021; 32:2737-2745 | PMID: 34379354
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Impact:
Abstract

Interventional occlusion of left atrial appendage in patients with atrial fibrillation. Gender-related outcomes in the German LAARGE Registry.

Kleinecke C, Lewalter T, Sievert H, Geist V, ... Senges J, Brachmann J
Introduction
Gender-based differences in atrial fibrillation have been identified, but limited data exist for patients undergoing left atrial appendage occluder (LAAO) implantation. This study reports gender-related periprocedural and 1-year outcomes of the prospective, multicenter German left atrial appendage occlusion registry (LAARGE).
Methods
LAARGE enrolled 641 patients who were scheduled for LAAO implantation from July 2014 to January 2016 in 38 hospitals in Germany. The data collected included demographics, clinical characteristics, details of implantation, and outcome. Efficacy and safety at 1-year follow-up were assessed by the occurrence of thrombembolic and bleeding events, as well as mortality.
Results
Of 638 patients undergoing LAAO implantation 38.9% were female and 61.1% male. Females were older (76.4 ± 8.2 [females] vs. 75.6 ± 7.7 [males], p = .042) and had a higher stroke risk (CHA2 DS2 -VASc score: 4.9 ± 1.5 vs. 4.3 ± 1.5, p < .001). In contrast, males suffered more often from coronary artery (33.1% vs. 53.8%, p < .001) and vascular disease (18.5% vs. 31.0%, p < .001). Technical success was high and similar for both genders (98.4% vs. 97.2%, p = .33). Severe periprocedural complications (6.9% vs. 3.1%, p = .032) occurred more often in females. At 1-year follow-up the rates of all-cause stroke (0.5% vs. 1.3%, p = .65) and severe bleeding (0.0% and 1.0%, p = .29) were low and comparable between the genders. Also, one-year all-cause mortality (9.2% vs. 13.1%, p = .14) did not differ significantly.
Conclusion
LAARGE documented in this elderly patient population undergoing LAAO implantation a higher rate of severe periprocedural complications in females. At 1-year follow-up similar efficacy and safety outcomes were observed for both genders.

© 2021 Wiley Periodicals LLC.

J Cardiovasc Electrophysiol: 29 Sep 2021; 32:2636-2644
Kleinecke C, Lewalter T, Sievert H, Geist V, ... Senges J, Brachmann J
J Cardiovasc Electrophysiol: 29 Sep 2021; 32:2636-2644 | PMID: 34314065
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Impact:
Abstract

Lead fixation mechanism impacts outcome of transvenous lead extraction: Data from the European Lead Extraction ConTRolled Registry.

Levi N, Bongiorni MG, Rav Acha M, Tovia-Brodie O, ... Glikson M, Michowitz Y
Aims
The aims of this study is to characterize the transvenous lead extraction (TLE) population with active (A) compared with passive fixation (PFix) leads and to compare the safety, efficacy, and ease of extracting active fixation (AFix) compared with PFix right atrial (RA) and right ventricular (RV) leads.
Methods and results
The European Lead Extraction ConTRolled Registry (ELECTRa) was analysed. Patients were divided into three groups; those with only AFix, only PFix, and combined Fix leads. Three outcomes were defined. Difficult extraction, complete radiological, and clinical success. Multivariate model was used to analyse the independent effect of Fix mechanism on these outcomes. The study included 2815 patients, 1456 (51.7%) with only AFix leads, 982 (34.9%) with only PFix leads, and 377 (13.4%) with combined Fix leads. Patients with AFix leads were younger with shorter lead dwelling time. Infection was the leading cause for TLE among the combined Fix group with lowest rates among AFix group. No difference in complications rates was noted between patients with only AFix vs. PFix leads. Overall, there were 1689 RA (1046 AFix and 643 PFix) and 2617 RV leads (1441 AFix and 1176 PFix). Multivariate model demonstrated that PFix is independently associated with more difficult extraction for both RA and RV leads, lower radiological success in the RA but has no effect on clinical success.
Conclusion
Mechanism of Fix impact the ease of TLE of RA and RV leads and rates of complete radiological success in the RA but not clinical success. These findings should be considered during implantation and TLE procedures.

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

Europace: 14 Oct 2021; epub ahead of print
Levi N, Bongiorni MG, Rav Acha M, Tovia-Brodie O, ... Glikson M, Michowitz Y
Europace: 14 Oct 2021; epub ahead of print | PMID: 34652415
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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: 08 Oct 2021; 23:1568-1576
Magni FT, Al-Jazairi MIH, Mulder BA, Klinkenberg T, ... Mariani MA, Blaauw Y
Europace: 08 Oct 2021; 23:1568-1576 | PMID: 34143871
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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, ... Camm AAJ, X-VeRT Steering Committee and Investigators
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: 08 Oct 2021; 23:1539-1547
Cappato R, Ezekowitz MD, Hohnloser SH, Meng IL, ... Camm AAJ, X-VeRT Steering Committee and Investigators
Europace: 08 Oct 2021; 23:1539-1547 | PMID: 34128075
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Impact:
Abstract

Assessment of the physical performance in children with asymptomatic pre-excitation.

Książczyk TM, Jaroń A, Pietrzak R, Werner B
Aims
Pre-excitation syndrome can lead to recurrent supraventricular tachycardias (SVTs) and carries a risk of sudden cardiac death (SCD). However, an underestimated consequence of antegrade conduction through an accessory pathway is fusion of intrinsic and accessory conduction that causes asynchronous activation and myocardial contraction that could be a cause for cardiac dysfunction and dilation. It is not known to what extent pre-excitation affects myocardial and physical performance in those patients. The aim of the study was to assess to what degree ventricular pre-excitation affects physical performance in children, using cardio-pulmonary exercise testing (CPET).
Methods and results
The study group consisted of 30 asymptomatic children, aged 8-17 years, with pre-excitation and no history or documentation of SVT compared to 31 healthy controls matched according to sex and age. All patients underwent routine cardiology assessment and then CPET. Echocardiography showed there were no differences in the left ventricular size and function between the study and control group. During the CPET both, patients and controls achieved maximal effort. Patients in the study group showed significantly lower values of VO2max and anaerobic threshold when compared to controls. The most affected subgroup was patients with persistent pre-excitation throughout the exercise.
Conclusions
Physical performance is affected in children with pre-excitation. This effect is stronger in patients with persistent delta wave observed throughout the exercise.

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

Europace: 13 Oct 2021; epub ahead of print
Książczyk TM, Jaroń A, Pietrzak R, Werner B
Europace: 13 Oct 2021; epub ahead of print | PMID: 34648619
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Impact:
Abstract

The use of social media for professional purposes by healthcare professionals: the #intEHRAct survey.

Guerra F, Linz D, Garcia R, Kommata V, ... Boveda S, Duncker D
Social media (SoMe) represents a medium of communication in everyday life and has gained importance for professional use among clinicians. In the #intEHRAct survey, we aimed to describe the use of SoMe by the healthcare community in a professional setting. The EHRA e-Communication Committee and the Scientific Initiatives Committee prepared a questionnaire and distributed it via newsletters, Twitter, LinkedIn, and Facebook. The survey consisted of 19 questions made on an individual basis and collected anonymously. Two hundred and eighty-five responders from 35 countries (72.3% male, age 49 ± 11 years old) completed the survey. Most respondents (42.7%) declared to use SoMe as passive users while 38.3% and 19.0% declared to share content on a non-daily and daily basis, respectively. The respondents estimated they spent a median of 5 (Q1-Q3: 2-10) h per week on SoMe. The most widely used SoMe was LinkedIn (60.8%), but the use of each platform was heterogeneous between countries. Among the advantages of SoMe, respondents indicated the chance of being updated on recent publications (66.0%), networking (48.5%), and the availability of rare or interesting cases (47.9%) as the most useful. Regarding the disadvantages of SoMe, the respondents underlined the loss of personal contact (40.7%), the inability to get \'hands-on\' training (38.7%), and the lack of control regarding quality of scientific evidence (37.1%). Social media is increasingly used for professional purposes for scientific updating, networking, and case-based learning. The results of this survey encourage scientific societies, journals, and authors to enhance the quality, reach and impact of scientific content provided through SoMe.

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

Europace: 08 Oct 2021; epub ahead of print
Guerra F, Linz D, Garcia R, Kommata V, ... Boveda S, Duncker D
Europace: 08 Oct 2021; epub ahead of print | PMID: 34626177
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Abstract

Remote monitoring data from cardiac implantable electronic devices predicts all-cause mortality.

Ahmed FZ, Sammut-Powell C, Kwok CS, Tay T, ... Martin GP, Taylor JK
Aims
To determine if remotely monitored physiological data from cardiac implantable electronic devices (CIEDs) can be used to identify patients at high risk of mortality.
Methods and results
This study evaluated whether a risk score based on CIED physiological data (Triage-Heart Failure Risk Status, \'Triage-HFRS\', previously validated to predict heart failure (HF) events) can identify patients at high risk of death. Four hundred and thirty-nine adults with CIEDs were prospectively enrolled. Primary observed outcome was all-cause mortality (median follow-up: 702 days). Several physiological parameters [including heart rate profile, atrial fibrillation/tachycardia (AF/AT) burden, ventricular rate during AT/AF, physical activity, thoracic impedance, therapies for ventricular tachycardia/fibrillation] were continuously monitored by CIEDs and dynamically combined to produce a Triage-HFRS every 24 h. According to transmissions patients were categorized into \'high-risk\' or \'never high-risk\' groups. During follow-up, 285 patients (65%) had a high-risk episode and 60 patients (14%) died (50 in high-risk group; 10 in never high-risk group). Significantly more cardiovascular deaths were observed in the high-risk group, with mortality rates across groups of high vs. never-high 10.3% vs. <4.0%; P = 0.03. Experiencing any high-risk episode was associated with a substantially increased risk of death [odds ratio (OR): 3.07, 95% confidence interval (CI): 1.57-6.58, P = 0.002]. Furthermore, each high-risk episode ≥14 consecutive days was associated with increased odds of death (OR: 1.26, 95% CI: 1.06-1.48; P = 0.006).
Conclusion
Remote monitoring data from CIEDs can be used to identify patients at higher risk of all-cause mortality as well as HF events. Distinct from other prognostic scores, this approach is automated and continuously updated.

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

Europace: 02 Oct 2021; epub ahead of print
Ahmed FZ, Sammut-Powell C, Kwok CS, Tay T, ... Martin GP, Taylor JK
Europace: 02 Oct 2021; epub ahead of print | PMID: 34601572
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Impact:
Abstract

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

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

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

Europace: 02 Oct 2021; epub ahead of print
Castiglione A, Hornyik T, Wülfers EM, Giammarino L, ... Baczkó I, Odening KE
Europace: 02 Oct 2021; epub ahead of print | PMID: 34601592
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Abstract

Leadless left ventricular endocardial pacing for CRT upgrades in previously failed and high-risk patients in comparison with coronary sinus CRT upgrades.

Sidhu BS, Sieniewicz B, Gould J, Elliott MK, ... Niederer SA, Rinaldi CA
Aims
Cardiac resynchronization therapy (CRT) upgrades may be less likely to improve following intervention. Leadless left ventricular (LV) endocardial pacing has been used for patients with previously failed CRT or high-risk upgrades. We compared procedural and long-term outcomes in patients undergoing coronary sinus (CS) CRT upgrades with high-risk and previously failed CRT upgrades undergoing LV endocardial upgrades.
Method and results
Prospective consecutive CS upgrades between 2015 and 2019 were compared with those undergoing WiSE-CRT implantation. Cardiac resynchronization therapy response at 6 months was defined as improvement in clinical composite score (CCS) and a reduction in LV end-systolic volume (LVESV) ≥15%. A total of 225 patients were analysed; 121 CS and 104 endocardial upgrades. Patients receiving WiSE-CRT tended to have more comorbidities and were more likely to have previous cardiac surgery (30.9% vs. 16.5%; P = 0.012), hypertension (59.2% vs. 34.7%; P < 0.001), chronic obstructive airways disease (19.4% vs. 9.9%; P = 0.046), and chronic kidney disease (46.4% vs. 21.5%; P < 0.01) but similar LV ejection fraction (30.0 ± 8.3% vs. 29.5 ± 8.6%; P = 0.678). WiSE-CRT upgrades were successful in 97.1% with procedure-related mortality in 1.9%. Coronary sinus upgrades were successful in 97.5% of cases with a 2.5% rate of CS dissection and 5.6% lead malfunction/displacement. At 6 months, 91 WiSE-CRT upgrades and 107 CS upgrades had similar improvements in CCS (76.3% vs. 68.5%; P = 0.210) and reduction in LVESV ≥15% (54.2% vs. 56.3%; P = 0.835).
Conclusion
Despite prior failed upgrades and high-risk patients with more comorbidities, WiSE-CRT upgrades had high rates of procedural success and similar improvements in CCS and LV remodelling with CS upgrades.

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

Europace: 08 Oct 2021; 23:1577-1585
Sidhu BS, Sieniewicz B, Gould J, Elliott MK, ... Niederer SA, Rinaldi CA
Europace: 08 Oct 2021; 23:1577-1585 | PMID: 34322707
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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: 08 Oct 2021; 23:1559-1567
Caixal G, Althoff T, Garre P, Alarcón F, ... Guasch E, Mont L
Europace: 08 Oct 2021; 23:1559-1567 | PMID: 33975341
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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: 08 Oct 2021; 23:1677-1684
Desteghe L, Hendriks JML, Heidbuchel H, Potpara TS, Lee GA, Linz D
Europace: 08 Oct 2021; 23:1677-1684 | PMID: 34000040
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Impact:
Abstract

HPSD ablation for AF high-power short-duration RF ablation for atrial fibrillation: A review.

Winkle RA
This manuscript reviews the literature for all in silico, ex vivo, in vitro, in vivo and clinical studies of high-power short-duration (HPSD) radiofrequency (RF) ablations. It reviews the biophysics of RF energy delivery applicable to HPSD and the use of surrogate endpoints to guide the duration of HPSD ablations. In silico modeling shows that a variety of settings in power, contact force and RF duration can result in the same surrogate endpoint value of ablation index and several HPSD combinations produce lesion volumes similar to a low-power long-duration (LPLD) RF application. HPSD lesions are broader with more endocardial effect and are slightly shallower but still transmural. The first 10 s of RF application is most important for lesion formation with diminishing effect beyond 20 s. The ideal contact force is 10-20 g with only a small effect beyond 30 g. In vitro and in vivo models confirm that HPSD makes transmural lesions that are often broader and shallower, and with proper settings, result in fewer steam pops than LPLD. One randomized trial shows better outcomes with HPSD and validates lesion size index as a surrogate endpoint. Clinical studies of HPSD using comparator groups of LPLD ablations uniformly show shorter procedure times and shorter total RF energy delivery for HPSD. HPSD generally has a higher first pass vein isolation rate and a lower acute vein reconnection rate than LPLD. Although not dramatically different from LPLD, long-term freedom from atrial fibrillation and complication rates seem slightly better with HPSD.

© 2020 Wiley Periodicals LLC.

J Cardiovasc Electrophysiol: 29 Sep 2021; 32:2813-2823
Winkle RA
J Cardiovasc Electrophysiol: 29 Sep 2021; 32:2813-2823 | PMID: 33382506
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Abstract

Protection of the esophagus during catheter ablation of atrial fibrillation.

Houmsse M, Daoud EG
Esophageal injury still occurs with high frequency during ablation of atrial fibrillation (AF). The purpose of this study is to provide a review of methods to protect the esophagus from injury during AF ablation. Despite advances in imaging and ablation, the potential risk of esophageal injury during AF ablation remains an important concern with a high occurrence of esophageal injury (≈15%). There have been numerous studies evaluating varied techniques for esophageal protection including active cooling and displacement of the esophagus. These techniques are reviewed in this manuscript as well as the role of esophageal protection in managing patients undergoing AF ablation procedure.

© 2021 Wiley Periodicals LLC.

J Cardiovasc Electrophysiol: 29 Sep 2021; 32:2824-2829
Houmsse M, Daoud EG
J Cardiovasc Electrophysiol: 29 Sep 2021; 32:2824-2829 | PMID: 33556991
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Impact:
Abstract

Concomitant treatment of atrial fibrillation during mitral valve surgery.

Halas M, Kruse J, McCarthy PM
Introduction
Surgical management of atrial fibrillation (AF) is a well-established method of preventing complications and late mortality in patients presenting with AF before mitral valve (MV) surgery. However, despite a substantial body of evidence and a Class I recommendation to apply surgical ablation (SA) concomitant to MV surgery, the utilization of SA remains low.
Methods
In this study, we sought to summarize the current trends in the SA of AF during MV surgery and update the medical community on its advantages, including perioperative mortality and morbidity, freedom from AF, as well as long-term survival and stroke rates.
Results
The data indicate that SA can be added with no increased risk (and perhaps a reduction in perioperative risk) and improved late survival compared to patients with AF left untreated during MV surgery.
Discussion
Inconsistent application of SA may be related to inaccurate perceptions regarding the complexity of the procedure itself, extended cross-clamp and bypass times with attendant increased risks, views that it is ineffective, and increased need for an early pacemaker.
Conclusion
Education in the proper performance of SA, including careful placement of the lesions and attainment of the full transmural effect, contributes to procedure success. Propagating the safety and positive outcomes may also address the concerns.

© 2021 Wiley Periodicals LLC.

J Cardiovasc Electrophysiol: 29 Sep 2021; 32:2873-2878
Halas M, Kruse J, McCarthy PM
J Cardiovasc Electrophysiol: 29 Sep 2021; 32:2873-2878 | PMID: 33783900
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Impact:
Abstract

Supervised Obesity Reduction Trial for AF ablation patients: results from the SORT-AF trial.

Gessler N, Willems S, Steven D, Aberle J, ... Eickholt C, Lüker J
Aims
Weight management seems to be beneficial for obese atrial fibrillation (AF) patients; however, randomized data are sparse. Thus, this study aimed to investigate the influence of weight reduction on AF ablation outcomes.
Methods and results
SORT-AF is an investigator-sponsored, prospective, randomized, multicentre, and clinical trial. Patients with symptomatic AF (paroxysmal or persistent) and body mass index (BMI) 30-40 kg/m2 underwent AF ablation and were randomized to either weight-reduction (group 1) or usual care (group 2), after sleep-apnoea-screening and loop recorder (ILR) implantation. The primary endpoint was defined as AF burden between 3 and 12 months after AF ablation. Overall, 133 patients (60 ± 10 years, 57% persistent AF) were randomized to group 1 (n = 67) and group 2 (n = 66), respectively. Complications after AF-ablation were rare (one stroke and no tamponade). The intervention led to a significant reduction of BMI (34.9 ± 2.6-33.4 ± 3.6) in group 1 compared to a stable BMI in group 2 (P < 0.001). Atrial fibrillation burden after ablation decreased significantly (P < 0.001), with no significant difference regarding the primary endpoint between the groups (P = 0.815, odds ratio: 1.143, confidence interval: 0.369-3.613). Further analyses showed a significant correlation between BMI and AF recurrence for patients with persistent AF compared with paroxysmal AF patients (P = 0.032).
Conclusion
The SORT-AF study shows that AF ablation is safe and successful in obese patients using continuous monitoring via ILR. Although the primary endpoint of AF burden after ablation did not differ between the two groups, the effects of weight loss and improvement of exercise activity were beneficial for obese patients with persistent AF demonstrating the relevance of life-style management as an important adjunct to AF ablation in this setting.
Trial registration number
NCT02064114.

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

Europace: 08 Oct 2021; 23:1548-1558
Gessler N, Willems S, Steven D, Aberle J, ... Eickholt C, Lüker J
Europace: 08 Oct 2021; 23:1548-1558 | PMID: 33895833
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Impact:
Abstract

Intraprocedural PRAETORIAN score for early assessment of S-ICD implantation: A proof-of-concept study.

Gasperetti A, Schiavone M, Biffi M, Casella M, ... Tilz RR, Forleo GB
Introduction
The PRAETORIAN score (PS) was developed to assess the implant position and predict defibrillation success of the subcutaneous implantable cardioverter defibrillators (S-ICD). The main critique moved to the routine use of PS has been its postprocedural timing, that limits its usefulness on procedure guidance. The aim of this proof-of-concept study was to assess the feasibility of an intraprocedural use of PS.
Methods
Forty consecutive patients undergoing S-ICD implantation were enrolled. Intraprocedural PS (IP-PS) obtained with fluoroscopy before closure of the pocket and postprocedural PS (PP-PS) obtained with two-views chest X-ray were compared. Intraprocedural data and PS were compared with the historic cohorts of the involved institutions.
Results
When assessing IP-PS and PP-PS, a complete overall agreement was observed (100%, 1.00-κ; p < .001). When assessing a per-step agreement, a very high-degree of concordance in evaluating Step 1 of the PS was observed (95%, 0.81-κ; p < .001). A complete agreement in Step 2-3 (100%, 1.00-κ; p < .001) of the PS was reported. In comparison with our historical cohort, procedural time in the IP-PS cohort did not increase (45 [41-52] vs. 45 [39-49] min; p = .351) while the expected increase in fluoroscopy time resulted scarce (15 [10-15] s).
Conclusion
An IP-PS can be reliably obtained using fluoroscopy guidance during S-ICD implantation, without a significant increase in procedural duration and may serve as guidance for implanting physicians, to avoid postprocedural S-ICD repositioning, leading to patient discomfort and significantly enhancing infective risks. IP-PS showed a very high agreement with the PP-PS obtained from two-views chest X-ray.

© 2021 Wiley Periodicals LLC.

J Cardiovasc Electrophysiol: 27 Sep 2021; epub ahead of print
Gasperetti A, Schiavone M, Biffi M, Casella M, ... Tilz RR, Forleo GB
J Cardiovasc Electrophysiol: 27 Sep 2021; epub ahead of print | PMID: 34582055
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Impact:
Abstract

Association of Global Cardiac Calcification with Atrial Fibrillation and Recurrent Stroke in Patients with Embolic Stroke of Undetermined Source.

Li TYW, Yeo LLL, Ho JSY, Leow AS, ... Tan BY, Sia CH
Background
Calcium deposits in the heart have been associated with cardiovascular events, mortality, stroke, and atrial fibrillation (AF). However, there is no accepted standard method for scoring cardiac calcifications. Existing methods have also not been validated for the assessment of patients with embolic stroke of undetermined source (ESUS). The aim of this study was to evaluate the association of various cardiac calcification scores with new-onset AF and stroke recurrence in a cohort of patients with ESUS.
Methods
In this study, 181 consecutive patients with stroke diagnosed with ESUS were identified and evaluated. They were followed for new-onset AF and ischemic stroke recurrence for a median duration of 2.1 years. Various echocardiographic cardiac calcification scores were assessed on transthoracic echocardiography performed during the evaluation of ESUS and subsequently assessed for their relation to AF detection and recurrent stroke. The echocardiographic calcium scores assessed were the (1) global cardiac calcium score (GCCS), (2) echocardiographic calcium score (eCS), (3) echocardiographic calcification score, (4) echocardiographic composite cardiac calcium score, and (5) total heart calcification score. Only two of these scoring schemes, GCCS and eCS, quantified the cardiac calcium burden.
Results
Higher calcium scores as measured by GCCS and eCS were found to be significantly associated with subsequent AF detection as well as recurrent ischemic stroke in patients with ESUS. The association with recurrent stroke remained significant even after adjustment for comorbidities and AF.
Conclusions
Higher cardiac calcification measured using the GCCS and eCS is independently associated with AF detection and recurrent ischemic stroke in patients with ESUS, and these scores can be useful markers for further risk stratification in patients with ESUS.

Copyright © 2021 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.

J Am Soc Echocardiogr: 29 Sep 2021; 34:1056-1066
Li TYW, Yeo LLL, Ho JSY, Leow AS, ... Tan BY, Sia CH
J Am Soc Echocardiogr: 29 Sep 2021; 34:1056-1066 | PMID: 33872703
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Impact:
Abstract

Intracardiac echocardiography- versus transesophageal echocardiography-guided left atrial appendage occlusion with Watchman FLX.

Gianni C, Horton RP, Della Rocca DG, Mohanty S, ... Sanchez JE, Natale A
Introduction
Watchman FLX has been recently approved for left atrial appendage occlusion (LAAO) in the US. Intracardiac echocardiography (ICE) - which is already commonly used to guide trans-septal access - can serve as an alternative to TEE, simplifying the procedure and reducing associated costs. Herein, we report our experience with ICE-guided LAAO with Watchman FLX.
Methods and results
This cohort study included the first 190 consecutive patients who underwent LAAO with Watchman FLX in our center. LAAO was successful in all patients without significant peri-procedural, device-related complications in either group. Compared to TEE, we observed a significant reduction in procedural times when using ICE. In addition, there was a potentially clinically relevant reduction in fluoroscopy dose, mainly secondary to fewer cine acquisition runs. At follow-up, no cases of device embolism were noted, whereas the rate of device-related thrombosis and peri-device leaks were comparable between groups.
Conclusion
ICE-guided LAAO with Watchman FLX is safe and feasible, with a significant reduction in procedural time and potential reduction in fluoroscopy dose when compared to TEE.

© 2021 Wiley Periodicals LLC.

J Cardiovasc Electrophysiol: 29 Sep 2021; 32:2781-2784
Gianni C, Horton RP, Della Rocca DG, Mohanty S, ... Sanchez JE, Natale A
J Cardiovasc Electrophysiol: 29 Sep 2021; 32:2781-2784 | PMID: 34411376
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Impact:
Abstract

Ventricular pacing and myocardial function in patient with congenital heart block.

Rangavajla G, Mulukutla S, Thoma F, Kancharla K, ... Jain SK, Saba S
Introduction
Pacing-induced cardiomyopathy (PICM) is a potential complication of chronic right ventricular (RV) pacing, but its characterization in adult patients is often complicated by pre-existing cardiomyopathy. This study investigated the incidence of PICM in patients with congenital heart block (cHB) who have conduction disease from birth without confounding pre-existing cardiac conditions.
Methods and results
This retrospective cohort analysis included 42 patients with cHB and baseline left ventricular ejection fraction (LVEF) ≥50%. Kaplan-Meier analysis was used to assess freedom from cardiomyopathy (defined as LVEF <50%) between paced and nonpaced patients. Patients were 26 ± 3 years old at first presentation, 64% were women and baseline LVEF was 60.0 ± 0.2%. Median follow-up from birth was 35 (interquartile range [IQR]: 20-42) years with a median of 6.7 years (IQR: 3.6-9.2) at our institution. Thirty-two patients received pacing at mean age 21 ± 3 years. Patients receiving a pacemaker (PM) were significantly more likely to develop a cardiomyopathy (p = .021) and no patient developed a cardiomyopathy in the absence of a PM. Four patients who developed a new cardiomyopathy were upgraded to biventricular pacing, leading to stabilization or improvement of LVEF.
Conclusion
In a relatively young and healthy cHB cohort, RV pacing is associated with a higher risk of developing a cardiomyopathy. These data confirm the deleterious effects of RV pacing on myocardial function in patients without pre-existing structural cardiac disease and has clinical implications to the management of patients with cHB.

© 2021 Wiley Periodicals LLC.

J Cardiovasc Electrophysiol: 29 Sep 2021; 32:2684-2689
Rangavajla G, Mulukutla S, Thoma F, Kancharla K, ... Jain SK, Saba S
J Cardiovasc Electrophysiol: 29 Sep 2021; 32:2684-2689 | PMID: 34409682
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Abstract

Brugada syndrome masked by complete left bundle branch block: A clinical and functional study of its association with the p.1449Y>H SCN5A variant.

Arana-Rueda E, Pezzotti MR, Pedrote A, Acosta J, ... García-Fernández N, Castellano A
SCN5A gene variants are associated with both Brugada syndrome and conduction disturbances, sometimes expressing an overlapping phenotype. Functional consequences of SCN5A variants assessed by patch-clamp electrophysiology are particularly beneficial for correct pathogenic classification and are related to disease penetrance and severity. Here, we identify a novel SCN5A loss of function variant, p.1449Y>H, which presented with high penetrance and complete left bundle branch block, totally masking the typical findings on the electrocardiogram. We highlight the possibility of this overlap combination that makes impossible an electrocardiographic diagnosis and, through a functional analysis, associate the p.1449Y>H variant to SCN5A pathogenicity.

© 2021 The Authors. Journal of Cardiovascular Electrophysiology published by Wiley Periodicals LLC.

J Cardiovasc Electrophysiol: 29 Sep 2021; 32:2785-2790
Arana-Rueda E, Pezzotti MR, Pedrote A, Acosta J, ... García-Fernández N, Castellano A
J Cardiovasc Electrophysiol: 29 Sep 2021; 32:2785-2790 | PMID: 34411358
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Abstract

Gender differences in patients with structural heart disease undergoing VT ablation.

Darma A, Bertagnolli L, Torri F, Lurz JA, ... Dinov B, Arya A
Introduction
This study sought to examine gender differences in patients with structural heart disease (SHD) referred for ablation of ventricular tachycardia (VT).
Background
Female patients are often underrepresented in large studies. Significant differences in the clinical presentation, treatment, and prognosis of female patients have been described in previous studies.
Methods and results
We investigated 88 female patients with SHD undergoing VT ablation (mean age 59 years, 56% nonischemic cardiomyopathy, mean left ventricular ejection fraction 35%, 82% in electrical storm). A case-control study with 88 male patients was performed and the results regarding clinical and procedural characteristics, acute and long-term results of the two groups were compared. The female patients had more arrhythmogenic substrate, as they more commonly presented with electrical storm (p = .016) and had a higher number of inducible VT morphologies during the procedure (p = .018). Moreover, the female patients were less likely to have an optimized heart failure medical treatment at baseline (p = .030) and required more time from the first manifestation of the VT to ablation referral (p = .034). Although fewer epicardial ablations were performed in female patients (p = .019), the two groups showed similar results regarding VT noninducibility as ablation endpoint (p = .844), major procedure-related complications (p = .719) and freedom from VT during follow-up (p = .268). Moreover, the overall mortality in the two groups was similar (p = .176). Advanced NYHA class was associated with worse transplant and assist-device-free survival in the female group.
Conclusion
Female patients presenting for VT ablation had more arrhythmogenic substrate and were less likely to have an optimized heart failure medical treatment. Nevertheless, the procedural acute and long-term outcomes between the two genders were similar.

© 2021 The Authors. Journal of Cardiovascular Electrophysiology Published by Wiley Periodicals LLC.

J Cardiovasc Electrophysiol: 29 Sep 2021; 32:2675-2683
Darma A, Bertagnolli L, Torri F, Lurz JA, ... Dinov B, Arya A
J Cardiovasc Electrophysiol: 29 Sep 2021; 32:2675-2683 | PMID: 34411387
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Abstract

CT-guided percutaneous epicardial access for ventricular tachycardia ablation: A proof-of-concept study.

Subramanian M, Ravilla VV, Yalagudri S, Saggu DK, ... d\'Avila A, Narasimhan C
Introduction
The objective of this study was to evaluate the safety and efficacy of preprocedural computed tomography (CT) to guide percutaneous epicardial puncture for catheter ablation of ventricular tachycardia.
Methods and results
A preprocedural CT was used to plan the site, angle, and depth of needle insertion during epicardial access in 10 consecutive patients undergoing ventricular tachycardia (VT) ablation. Adjacent structures (right ventricle, diaphragm, liver, colon, internal mammary artery) were visualized and the course of the needle was planned avoiding these structures. During epicardial access, a protractor was used to guide the angle of needle entry into the subxiphoid space. Postprocedural CT was performed to calculate the deviation between the planned and executed access and to assess for any collateral damage. Percutaneous epicardial access was obtained successfully in all the patients using anterior (n = 4) and inferior (n = 6) approaches. The planned site and angle of puncture was more caudal (2.9 ± 0.9 vs. 3.7 ± 0.7 cm, p = .021) and acute (61.7 ± 5.8 vs. 49.0 ± 5.4°, p = .011) for an anterior approach compared to an inferior approach, respectively. Postprocedure CT revealed minimal deviation of the puncture site (5.4 ± 1.0 mm), angle (5.4 ± 1.2°), and length of needle insertion (0.5 ± 0.2 cm). With regard to the site of entry in the pericardial space, there was a deviation of 5.9 ± 1.1, 6.1 ± 1.1, and 5.8 ± 1.4 mm in the x, y, and z dimensions, respectively. In eight patients with minimal deviation between planned and executed access, there was no collateral injury to adjacent viscera or vessels. In two patients with increased deviation of angle and length of needle insertion, there was entry through the diaphragm during inferior access.
Conclusions
Utilizing pre-procedural CT planning may aid in the success and safety of percutaneous epicardial access during VT ablation.

© 2021 Wiley Periodicals LLC.

J Cardiovasc Electrophysiol: 29 Sep 2021; 32:2665-2672
Subramanian M, Ravilla VV, Yalagudri S, Saggu DK, ... d'Avila A, Narasimhan C
J Cardiovasc Electrophysiol: 29 Sep 2021; 32:2665-2672 | PMID: 34405472
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Abstract

\"Retained wire femoral lead removal and fibroplasty\" for obtaining venous access in patients with refractory venous obstruction.

Brar V, Worley SJ, Eldadah Z, O Donoghue S, ... Bansal S, Oza S
Background
Patients with wire and catheter refractory venous occlusion are traditionally referred for pectoral transvenous lead extraction (TLE) to obtain venous access. TLE causes 1-2 mm circumferential mechanical or laser destruction of tissue surrounding the lead(s). This not only exposes the patient to the risk of major complications but also can damage nontargeted leads. We present a series of patients where retained wire femoral lead removal and fibroplasty was used to obtain venous access in patients with refractory obstruction.
Methods
Between 2008 and 2021, we identified 17 patients where retained wire lead removal followed by fibroplasty was used to retain venous access. Demographic and procedural data were obtained by retrospective review of patient charts.
Results
We were able to successfully obtain venous access in all 17 patients in whom this technique was attempted. In two patients the target lead was less than or equal to 1 year old. In the remaining 15 patients, the average dwell time of the target lead(s) was 6 years. There were no procedure-related complications, and no changes in the parameters of other leads were noted.
Conclusion
Retained wire femoral lead removal and fibroplasty is safe and highly efficacious at obtaining venous access in patients with refractory venous occlusion. If the target lead(s) is less than or equal to 1 year old, this technique can help obtain venous access at the time of the initial surgery, hence avoiding the need for TLE. Furthermore, in patients referred for TLE to obtain venous access, this technique by avoiding the use of TLE tools spares the patient of the associated risks.

© 2021 Wiley Periodicals LLC.

J Cardiovasc Electrophysiol: 29 Sep 2021; 32:2729-2736
Brar V, Worley SJ, Eldadah Z, O Donoghue S, ... Bansal S, Oza S
J Cardiovasc Electrophysiol: 29 Sep 2021; 32:2729-2736 | PMID: 34374160
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Abstract

Utility of hot-balloon-based pulmonary vein isolation under balloon surface temperature monitoring: First clinical experience.

Nakahara S, Wakamatsu Y, Fukuda R, Hori Y, ... Taguchi I, Okumura Y
Introduction
A new hot balloon system that registers balloon surface temperature (BST) during energy delivery is now available for clinical use in Japan. This study sought to investigate the utility of BST measurement for achievement of pulmonary vein isolation (PVI) by a single-shot energy delivery strategy during hot balloon ablation (HBA).
Methods
We applied and tested the system in 30 consecutive patients undergoing HBA for paroxysmal or early-persistent atrial fibrillation (AF). We also performed real-time PV potential monitoring using a circular catheter.
Results
Acute PVI was achieved with single hot balloon shots in 88% (106/120) of the PVs. Real-time BSTs and PV potentials were recorded in all cases. Mean BST at documentation of PVI was 49.4°C, and acute reconnections were observed in most cases (86%, 12/14) in which the single-shot technique was ineffective. Time-to-isolation (TTI) (23.1 ± 8.7 s vs. 36.3 ± 9.3 s, p < .01) and median BST (59.9 ± 2.6°C vs. 55.7 ± 1.9°C, p < .01) differed significantly between cases in which PVI was achieved (vs. those in which PVI was not achieved). Multivariable analysis revealed strong association between both TTI and median BST and acute PVI. The best median BST cutoff value for achieving PVI with a single shot was >58.7°C (sensitivity 67.0%, specificity 100%).
Conclusion
Our data suggest that real-time BST monitoring during energy applications is useful for predicting achievement of acute PVI by a single shot during HBA.

© 2021 Wiley Periodicals LLC.

J Cardiovasc Electrophysiol: 29 Sep 2021; 32:2625-2635
Nakahara S, Wakamatsu Y, Fukuda R, Hori Y, ... Taguchi I, Okumura Y
J Cardiovasc Electrophysiol: 29 Sep 2021; 32:2625-2635 | PMID: 34350665
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Abstract

Outcome of transvenous lead extraction in patients on minimally interrupted periprocedural direct oral anticoagulation therapy.

Issa ZF, Elayyan MAM
Background
Direct oral anticoagulants (DOACs) have increasingly been used for several indications for systemic anticoagulation in patients with cardiac implantable electronic devices (CIEDs). The optimal management of anticoagulation therapy in patients undergoing transvenous lead extraction (TLE) procedures remains uncertain.
Objectives
The aim of this study was to evaluate the feasibility and safety of TLE during minimally interrupted DOAC therapy.
Methods
This is a single-center retrospective study of all patients who underwent TLE of a pacemaker or implantable cardioverter-defibrillator lead while on DOAC therapy. In patients deemed to be at high thromboembolic risk, the last DOAC dose was administered the morning of the day before the procedure (regardless of the type of DOAC) and was restarted as soon as possible after the procedure, without bridging with parenteral anticoagulation.
Results
During the study period, a total of 84 patients underwent TLE while on minimally interrupted DOAC therapy (54% female, mean age: 74 ± 12 years). TLE was attempted for 161 leads, with a median lead dwell time of 61 months (interquartile range, 38-101). Complete procedural success was achieved for 156 leads (96.9%) and partial success for additional two leads (1.2%). One patient developed RV perforation and required pericardiocentesis and blood transfusion, but no surgical repair. Two patients developed pocket hematomas requiring invasive evacuation. No systemic or venous thromboembolic events were observed. There was no in-hospital mortality.
Conclusions
In selected CIED patients at high risk for thromboembolism, TLE during minimally interrupted DOAC therapy may be considered when performed at experienced centers.

© 2021 Wiley Periodicals LLC.

J Cardiovasc Electrophysiol: 29 Sep 2021; 32:2722-2728
Issa ZF, Elayyan MAM
J Cardiovasc Electrophysiol: 29 Sep 2021; 32:2722-2728 | PMID: 34322933
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Abstract

Current practice in transvenous lead extraction in Latin America: Latin American Heart Rhythm Association survey.

Diaz JC, Romero J, Costa R, Cuesta A, ... Niño CD, Mazzetti H
Background
Transvenous lead extraction (TLE) is standard of care for the management of patients with cardiac implantable electronic device infection or lead-related complications. Currently, objective data on TLE in Latin America is lacking.
Objective
To describe the current practice standards in Latin American centers performing TLE.
Methods
An online survey was sent through the mailing list of the Latin American Heart Rhythm Society. Online reminders were sent through the mailing list; duplicate answers were discarded. The survey was available for 1 month, after which no more answers were accepted.
Results
A total of 48 answers were received, from 44 different institutions (39.6% from Colombia, 27.1% from Brazil), with most respondents (82%) being electrophysiologists. Twenty-nine institutions (66%) performed <10 lead extractions/year, with 7 (16%) institutions not performing lead extraction. Although most institutions in which lead extraction is performed reported using several tools, mechanical rotating sheaths were cited as the main tool (66%) and only 13% reported the use of laser sheaths. Management of infected leads was performed according to current guidelines.
Conclusion
This survey is the first attempt to provide information on TLE procedures in Latin America and could provide useful information for future prospective registries. According to our results, the number of centers performing high volume lead extraction in Latin America is smaller than that reported in other continents, with most interventions performed using mechanical tools. Future prospective registries assessing acute and long-term success are needed.

© 2021 Wiley Periodicals LLC.

J Cardiovasc Electrophysiol: 29 Sep 2021; 32:2715-2721
Diaz JC, Romero J, Costa R, Cuesta A, ... Niño CD, Mazzetti H
J Cardiovasc Electrophysiol: 29 Sep 2021; 32:2715-2721 | PMID: 34288220
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