Journal: Heart Rhythm

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Abstract

Identification of patients at risk of sudden cardiac death in congenital heart disease. The PRospEctiVE study on implaNTable cardIOverter defibrillator therapy and suddeN cardiac death in Adults with Congenital Heart Disease: PREVENTION-ACHD.

Vehmeijer JT, Koyak Z, Leerink JM, Zwinderman AH, ... Mulder BJM, de Groot JR
Background
Sudden cardiac death (SCD) is the main preventable cause of death in adult congenital heart disease (ACHD) patients. Since robust risk stratification methods are lacking, we developed a risk score to predict SCD in ACHD patients: PREVENTION-ACHD.
Objective
to prospectively study predicted SCD risk using PREVENTION-ACHD and actual SCD and sustained ventricular tachycardia/ventricular fibrillation (VT/VF)rates in ACHD patients.
Methods
The PREVENTION-ACHD risk-score assigns one point each to: coronary artery disease, NYHA class II/III heart failure, supraventricular tachycardia, systemic ejection fraction <40%, subpulmonary ejection fraction <40%, QRS duration ≥120 msec, QT dispersion ≥70 msec. SCD-risk was calculated for each patient. An annual predicted risk ≥3% constituted high-risk. The primary outcome was SCD or VT/VF after 2 years. The secondary outcome was SCD.
Results
783 consecutive ACHD patients (31% left-sided lesions, 18% tetralogy of Fallot, 14% closed ASD), median age 36 years and 52% male, were included. PREVENTION-ACHD identified 58 high-risk patients. Eight patients (four at high-risk) experienced the primary outcome. The Kaplan-Meier estimates were 7% (95%CI 0.1-13.3%) in the high-risk and 0.6% (95%CI 0-1.1%) in the low-risk group, HR 12.5 (95%CI 3.1-50.9, p<0.001). The risk-score\'s sensitivity was 0.5, specificity 0.93, resulting in a C-statistic of 0.75 (95%CI 0.57-0.90). The HR for SCD was 12.4 (95%CI 1.8-88.1, p=0.01); sensitivity and specificity were 0.5 and 0.92, and the C-statistic 0.81 (95%CI 0.67-0.95).
Conclusion
The PREVENTION-ACHD risk-score provides greater accuracy in SCD or VT/VF risk stratification compared to current guideline indications and identifies ACHD patients who may benefit from preventive ICD implantation.

Copyright © 2021. Published by Elsevier Inc.

Heart Rhythm: 15 Jan 2021; epub ahead of print
Vehmeijer JT, Koyak Z, Leerink JM, Zwinderman AH, ... Mulder BJM, de Groot JR
Heart Rhythm: 15 Jan 2021; epub ahead of print | PMID: 33465514
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Abstract

Causes of syncopal recurrences in patients treated with permanent pacing for bradyarrhythmic syncope: findings from the SYNCOPACED registry.

Palmisano P, Dell\'Era G, Pellegrino PL, Ammendola E, ... Accogli M, Italian Association of Arrhythmology and Cardiac Pacing (AIAC)
Background
Few studies have examined the causes of syncope/collapse recurrences in patients with a previously implanted pacemaker for bradyarrhythmic syncope.
Objective
To assess the causes of syncope/collapse recurrences after pacemaker implantation for bradyarrhythmic syncope in a large patient population.
Methods
Prospective, multicenter, observational registry enrolling 1,364 consecutive patients undergoing pacemaker implantation for bradyarrhythmic syncope. During follow-up, the time to the first syncope/collapse recurrence was recorded. Patients with syncope/collapse recurrences underwent a predefined diagnostic work-up aimed at establishing the mechanism of syncope/collapse.
Results
During a median follow-up of 50 months, 213 patients (15.6%) reported at least one syncope/collapse recurrence. The risk of syncope/collapse recurrence was highest in patients who underwent implantation for cardioinhibitory vasovagal syncope (26.4%), followed by unexplained syncope and chronic bifascicular block (21.5%), cardioinhibitory carotid sinus syndrome (17.2%), atrial fibrillation needing pacing (15.5%), atrioventricular block (13.6%), and sinus node disease (12.5%) (p=0.017). The most frequent cause of syncope/collapse recurrence was reflex syncope (27.7%), followed by orthostatic hypotension (26.3%), pacemaker/lead malfunction (5.6%), structural cardiac disease (5.2%), and atrial and ventricular tachyarrhythmias (4.7 and 3.8%, respectively). In 26.8% of cases, the mechanism of syncope/collapse remained unexplained.
Conclusion
In patients receiving a pacemaker for bradyarrhythmic syncope, reflex syncope and orthostatic hypotension are the most frequent mechanisms of syncope/collapse recurrence after implantation. Pacing system malfunction, structural cardiac diseases and tachyarrhythmias are rare mechanisms. The mechanism remains unexplained in more than 25% of patients.

Copyright © 2021. Published by Elsevier Inc.

Heart Rhythm: 15 Jan 2021; epub ahead of print
Palmisano P, Dell'Era G, Pellegrino PL, Ammendola E, ... Accogli M, Italian Association of Arrhythmology and Cardiac Pacing (AIAC)
Heart Rhythm: 15 Jan 2021; epub ahead of print | PMID: 33465512
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Abstract

Cardiac Resynchronization Therapy and Ventricular Tachyarrhythmia Burden.

Tankut S, Goldenberg I, Kutyifa V, Zareba W, ... Aktas MK, Younis A
Background
Cardiac resynchronization therapy-defibrillator (CRT-D) may reduce the incidence of first ventricular tachyarrhythmia (VTA) in patients with heart failure (HF) and left bundle-branch-block (LBBB).
Objective
To assess the effect of CRT-D on VTA burden in LBBB patients.
Methods
We included 1281 patients with LBBB from MADIT-CRT. VTA was defined as any treated or monitored sustained ventricular tachycardia (VT≥180 bpm) or ventricular fibrillation (VF). Life-threatening VTA was defined as VT≥200 bpm or VF. VTA recurrence was assessed using the Andersen-Gill model.
Results
During a mean follow-up of 2.5 years, 964 VTA episodes occurred in 264 (21%) patients. The VTA rate per 100 person-years was significantly lower in the CRT-D group when compared with the ICD group (20 vs. 34; respectively; p<0.01). Multivariate analysis demonstrated that CRT-D treatment was associated with a 32% risk reduction for VTA recurrence (HR=0.68; 95%CI 0.57-0.82; p<0.001), 57% risk reduction for recurrent life-threatening VTA, 54% risk reduction for recurrent appropriate ICD-shocks, and a 25% risk reduction for the combined endpoint of VTA and death. The effect of CRT on VTA burden was consistent among all tested subgroups, but was more pronounced among NYHA class I patients. Landmark analysis showed that at 2 years, the cumulative probability of death subsequent to year one was highest (16%) among patients who had ≥2 VTA events during their first year.
Conclusion
In patients with LBBB and HF, early intervention with CRT-D reduces mortality, VTA burden, and frequency of multiple appropriate ICD shocks. VTA burden is a powerful predictor of subsequent mortality.

Copyright © 2021. Published by Elsevier Inc.

Heart Rhythm: 09 Jan 2021; epub ahead of print
Tankut S, Goldenberg I, Kutyifa V, Zareba W, ... Aktas MK, Younis A
Heart Rhythm: 09 Jan 2021; epub ahead of print | PMID: 33440249
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Abstract

Epigenetics in atrial fibrillation: a reappraisal.

Puertas RD, Arora R, Rome S, Asatryan B, Roderick HL, Chevalier P

Atrial fibrillation (AF) is the most common cardiac arrhythmia and an important cause of morbidity and mortality globally. Atrial remodeling includes changes in ion channel expression and function, structural alterations, and neural remodeling, which create an arrhythmogenic milieu resulting in AF initiation and maintenance. Current therapeutic strategies for AF involving ablation and antiarrhythmic drugs are associated with a relatively high recurrence and pro-arrhythmic side effects respectively. Over the last two decades, to overcome these issues, research has sought to identify the genetic basis for AF thereby gaining insight into the regulatory mechanisms governing its pathophysiology. Despite identification of multiple gene loci associated with AF, none have thus far led to a therapy, indicating additional contributors to pathology. Recently, in the context of expanding knowledge of the epigenome (DNA methylation, histone modifications, and noncoding RNAs), its potential involvement in the onset and progression of AF pathophysiology has started to emerge. Probing the role of various epigenetic mechanisms that contribute to AF may improve our knowledge of this complex disease, identify potential therapeutic targets and facilitate targeted therapies. Here, we provide a comprehensive review of growing epigenetic features involved in AF pathogenesis, and summarize the emerging epigenomic targets for therapy that have been explored in preclinical models of AF.

Copyright © 2021. Published by Elsevier Inc.

Heart Rhythm: 09 Jan 2021; epub ahead of print
Puertas RD, Arora R, Rome S, Asatryan B, Roderick HL, Chevalier P
Heart Rhythm: 09 Jan 2021; epub ahead of print | PMID: 33440248
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Abstract

Connexin45 (GJC1) loss-of-function mutation contributes to familial atrial fibrillation and conduction disease.

Li RG, Xu YJ, Ye WG, Li YJ, ... Yang YQ, Bai D
Background
Atrial fibrillation (AF) represents the most common clinical cardiac arrhythmia and substantially increases the risk for cerebral stroke, heart failure and death. Although causative genes for AF have been identified, the genetic determinants for AF remain largely unclear.
Objective
This study aimed to investigate the molecular basis of AF in a Chinese kindred.
Methods
A four-generation family with autosomal-dominant AF and other arrhythmias (atrioventricular block, sinus bradycardia and premature ventricular contractions) was recruited. Genome-wide scan with microsatellite markers and linkage analysis as well as whole-exome sequencing analysis were performed. Electrophysiological characteristics and subcellular localization of the AF-linked mutant were analyzed using dual whole-cell patch clamps and confocal microscopy, respectively.
Results
A novel genetic locus for AF was mapped to chromosome 17q21.3, a 3.23-cM interval between markers D17S951 and D17S931, with a maximum two-point logarithm of odds (LOD) score of 4.2144 at marker D17S1868. Sequencing analysis revealed a heterozygous mutation in the mapping region, NM_005497.4:c.703A>T;p.(M235L), in the GJC1 gene encoding connexin45 (Cx45). The mutation co-segregated with AF in the family and was absent in 632 control individuals. The mutation decreased the coupling conductance in cell pairs (M235L/M235L, M235L/Cx45, M235L/Cx43 and M235L/Cx40), likely due to impaired subcellular localization.
Conclusion
This study defines a novel genetic locus for AF on chromosome 17q21.3, and reveals a loss-of-function mutation in GJC1 (Cx45) contributing to AF and other cardiac arrhythmias.

Copyright © 2021. Published by Elsevier Inc.

Heart Rhythm: 07 Jan 2021; epub ahead of print
Li RG, Xu YJ, Ye WG, Li YJ, ... Yang YQ, Bai D
Heart Rhythm: 07 Jan 2021; epub ahead of print | PMID: 33429106
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Abstract

Catheter Ablation of the Left and Right Atrial Appendages without Isolation in Persistent Atrial Fibrillation.

Ghannam M, Jame S, Jongnarangsin K, Cheng YW, ... Morady F, Chugh A
Background
Electrical isolation of the left atrial appendage (LAA) improves outcomes of patients with persistent atrial fibrillation (AF) but may increase the risk of thromboembolism.
Objective
This study describes a method to map and ablate appendage drivers without complete electrical isolation.
Methods
One hundred and thirteen patients underwent an ablation procedure for persistent AF. The procedure was performed during AF, and consisted of pulmonary vein (PV) and posterior left atrial (LA) isolation, and ablation of the LAA. The right atrium (RA) was targeted in patients with a right-to-left gradient in cycle length (CL). The endpoint of appendage ablation was CL slowing or AF termination but not complete isolation.
Results
Among the 113 patients (mean age, 64.6±8.6; ejection fraction, 54±13%; LA diameter 46±6.5 mm), radiofrequency ablation (RFA) terminated AF in 51 patients (45%). RA ablation was performed in 41 patients (36%) at the index or repeat procedure. The mean AF CL in the RAA was shorter than that in the LAA (160±32 ms vs. 186±29 ms, p<0.01) in these patients. The most frequent target in the RA was the RAA (CLs of 50-60 ms). Discontinuing RFA upon AF termination or conduction slowing prevented LAA isolation. After a follow-up of 24±15 months, 89 patients (78%) remained arrhythmia-free without antiarrhythmic medications.
Conclusions
An ablation strategy guided by the AF CL addresses LAA drivers without complete electrical isolation, and also helps identify the RAA as a source of persistent AF.

Copyright © 2021. Published by Elsevier Inc.

Heart Rhythm: 07 Jan 2021; epub ahead of print
Ghannam M, Jame S, Jongnarangsin K, Cheng YW, ... Morady F, Chugh A
Heart Rhythm: 07 Jan 2021; epub ahead of print | PMID: 33429104
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Abstract

Stimulation and Propagation of Activation in Conduction Tissue: Implications for Left Bundle Branch Area Pacing.

Niri A, Bhaskaran A, Asta J, Massé S, ... Waxman M, Nanthakumar K
Background
Characterizing wave-front generation and impulse conduction in left bundle (LB) has implications for Left Bundle Branch Area Pacing (LBBAP).
Objective
To describe the pacing characteristics of LB and to study the role of pacing pulse width (PW) to overcome Left Bundle Branch Block (LBBB).
Methods
Twenty, fresh ovine heart slabs containing well developed and easily identifiable tissues of the conduction system were used for the study. LB stimulation, activation and propagation were studied under baseline conditions, simulated conduction slowing, conduction block and fascicular block.
Results
The maximum radius of the LB early activation increased to up to 13.4 ± 2.4mm from the pacing stimulus and the time from stimulus to evoked potential shortened when the pacing PW was increased from 0.13 to 2ms at baseline. Conduction slowing and block induced by cooling could be resolved by increasing the pacing PW from 0.25ms to 1.5ms over a distance of 10 ± 1.5mm from the pacing stimulus. The LB Strength-Duration (SD) curve was shifted to the left of myocardial SD curve.
Conclusion
Increasing the PW resolved conduction slowing, block and bypassed experimental model of fascicular block in the LB. Precise positioning of LB lead in LV sub-endocardium is not mandatory in LBBAP as the Strength-Duration curve of LB was shifted to left of that of myocardium and could be captured from a distance by optimizing the PW.

Copyright © 2021. Published by Elsevier Inc.

Heart Rhythm: 04 Jan 2021; epub ahead of print
Niri A, Bhaskaran A, Asta J, Massé S, ... Waxman M, Nanthakumar K
Heart Rhythm: 04 Jan 2021; epub ahead of print | PMID: 33418128
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Abstract

Intermediate Term Performance and Safety of His Bundle Pacing Leads: A Single Center Experience.

Teigeler T, Kolominsky J, Vo C, Shepard RK, ... Ellenbogen KA, Padala SK
Background
The short-term safety, feasibility, and performance of the His bundle pacing (HBP) leads have been reported, however, their longer-term performance beyond 1 year remains unclear.
Objective
The objective of this study was to examine the intermediate-term performance and safety of HBP.
Methods
All HBP lead implants at Virginia Commonwealth University between 01-2014 and 01-2019 were analyzed. HBP was performed using a SelectSecure 3830-69 cm pacing lead (Medtronic, Minneapolis, MN).
Results
Of 295 attempts, successful HBP implantation (selective or non-selective) was seen in 274 (93%) cases. The mean follow-up duration was 22.8±19.5 months (median 19.5 months, IQR 11-33 months). Mean age was 69±15 years, 58% were males, and ejection fraction <50% was noted in 30%. Indications for pacemaker included sick sinus syndrome in 41%, atrioventricular block in 36%, cardiac resynchronization therapy in 7%, and refractory atrial fibrillation in 15%. Selective HBP was achieved in 33%. The mean HBP capture threshold at implant was 1.1±0.9V at 0.8±0.2ms which significantly increased at chronic follow-up to 1.7±1.1V at 0.8±0.3ms (P<0.001). Threshold was ≥2.5V in 24% patients, and 28% had an increase in HBP threshold ≥1V. Loss of His bundle capture at follow-up (septal RV pacing) was seen in 17%. There was a total of 31 (11%) lead revisions, primarily for unacceptably high thresholds.
Conclusion
While HBP can prevent or improve pacing induced cardiomyopathy, the elevated capture thresholds, loss of His bundle capture, and lead revision rates at intermediate follow-up are concerning. Longer-term follow-up data from multiple centers are needed.

Copyright © 2021. Published by Elsevier Inc.

Heart Rhythm: 04 Jan 2021; epub ahead of print
Teigeler T, Kolominsky J, Vo C, Shepard RK, ... Ellenbogen KA, Padala SK
Heart Rhythm: 04 Jan 2021; epub ahead of print | PMID: 33418127
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Abstract

Left ventricular summit arrhythmias with an abrupt V transition: Anatomy of the aortic interleaflet triangle vantage point.

Liao H, Wei W, Tanager KS, Miele F, ... Husain AN, Tung R
Background
While early precordial electrocardiographic (ECG) characteristics are useful to differentiate left-sided from the right-sided outflow tract ventricular arrhythmia (OTVA), few patterns predict an origin from the septal margin of the left ventricular (LV) summit.
Objective
The purpose of this study was to report mapping and ablation characteristics of a new ECG pattern with left bundle branch morphology and an abrupt R-wave transition in lead V (ATV3).
Methods
Over a 3-year period, 78 consecutive patients (mean age 57±15 years; 35% female) with OTVA were referred for mapping and ablation. Twenty patients (26%) exhibited an ATV3 pattern, of whom 65% failed prior ablation.
Results
Ninety-two percent of patients with ATV3 that underwent simultaneous epicardial and endocardial mapping demonstrated an intramural or epicardial site of origin. Eighty percent of OTVA with ATV3 was eliminated by ablation from the vantage point of the interleaflet triangle below the right-left coronary junction. The ATV3 pattern showed higher sensitivity, specificity, predictive value, and accuracy than validated ECG criteria (notch or \"w\" pattern in lead V, qrS pattern in leads V through V, and pattern break V) for predicting successful ablation in the region of the anterior LV ostium. At 12±11 months, freedom from ventricular arrhythmia recurrence was 89% and 82% in the ATV3 and control groups, respectively.
Conclusion
ATV3 is a simple and distinct ECG pattern indicative of a site of origin from the septal margin of the LV summit. The right-left aortic interleaflet triangle vantage point was effective to eliminate OTVA with ATV3 that overwhelmingly exhibited the earliest activation from the epicardium or mid-myocardium. Test characteristics for ATV3 were superior to ECG patterns validated for the anterior LV ostium.

Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Heart Rhythm: 30 Dec 2020; 18:10-19
Liao H, Wei W, Tanager KS, Miele F, ... Husain AN, Tung R
Heart Rhythm: 30 Dec 2020; 18:10-19 | PMID: 32707175
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Abstract

Sex-specific I activation in rabbit ventricles with drug-induced QT prolongation.

Wu AZ, Chen M, Yin D, Everett TH, ... Qu Z, Chen PS
Background
Female sex is a known risk factor for drug-induced long QT syndrome (diLQTS). We recently demonstrated a sex difference in apamin-sensitive small-conductance Ca-activated K current (I) activation during β-adrenergic stimulation.
Objective
The purpose of this study was to test the hypothesis that there is a sex difference in I in the rabbit models of diLQTS.
Methods
We evaluated the sex difference in ventricular repolarization in 15 male and 22 female Langendorff-perfused rabbit hearts with optical mapping techniques during atrial pacing. HMR1556 (slowly activating delayed rectifier K current [I] blocker), E4031 (rapidly activating delayed rectifier K current [I] blocker) and sea anemone toxin (ATX-II, late Na current [I] activator) were used to simulate types 1-3 long QT syndrome, respectively. Apamin, an I blocker, was then added to determine the magnitude of further QT prolongation.
Results
HMR1556, E4031, and ATX-II led to the prolongation of action potential duration at 80% repolarization (APD) in both male and female ventricles at pacing cycle lengths of 300-400 ms. Apamin further prolonged APD (pacing cycle length 350 ms) from 187.8±4.3 to 206.9±7.1 (P=.014) in HMR1556-treated, from 209.9±7.8 to 224.9±7.8 (P=.003) in E4031-treated, and from 174.3±3.3 to 188.1±3.0 (P=.0002) in ATX-II-treated female hearts. Apamin did not further prolong the APD in male hearts. The Ca transient duration (CaTD) was significantly longer in diLQTS than baseline but without sex differences. Apamin did not change CaTD.
Conclusion
We conclude that I is abundantly increased in female but not in male ventricles with diLQTS. Increased I helps preserve the repolarization reserve in female ventricles treated with I and I blockers or I activators.

Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Heart Rhythm: 30 Dec 2020; 18:88-97
Wu AZ, Chen M, Yin D, Everett TH, ... Qu Z, Chen PS
Heart Rhythm: 30 Dec 2020; 18:88-97 | PMID: 32707174
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Abstract

Clinical significance of myocardial scar in patients with frequent premature ventricular complexes undergoing catheter ablation.

Ghannam M, Yokokawa M, Liang JJ, Cochet H, ... Morady F, Bogun F
Background
Frequent premature ventricular complexes (PVCs) can result in PVC-induced cardiomyopathy (PICM). Scarring has been described in patients with frequent PVCs in the absence of apparent heart disease and in patients with known cardiomyopathy.
Objective
The purpose of this study was to determine the impact of focal myocardial scarring as detected by cardiac magnetic resonance imaging (CMR) on PICM, procedural outcomes, and recovery of left ventricular function in patients with frequent PVCs.
Methods
A total of 351 consecutive patients (181 men; age 53 ± 15 years; ejection fraction [EF] 51% ± 12%) with frequent PVCs referred for ablation were included. CMR was performed in all patients before the ablation procedure. A ≥10% increase in EF or normalization of a previously abnormal EF was defined as evidence of PICM.
Results
Myocardial scarring was present in 134 of 351 patients (38%); 66 of 134 patients (49%) with scarring and 54 of 217 patients (25%) without scarring had improvement or normalization of EF after ablation. The presence of myocardial scarring, PVC burden >22%, male sex, asymptomatic status, and PVC QRS width >150 ms were associated with PICM by univariate analysis (P <.01 for all). The presence of scar was independently associated with PICM (odds ratio 2.2; 95% confidence interval 1.3-3.7; P <.005). The success rate of PVC ablation was lower in patients with scarring than in patients without focal scarring (mean 70% vs 82%; P <.01).
Conclusion
Focal scar defined by CMR is independently associated with PICM. Although ablation outcomes are worse in the presence of scarring, EF recovery can occur in most of these patients after ablation.

Copyright © 2020. Published by Elsevier Inc.

Heart Rhythm: 30 Dec 2020; 18:20-26
Ghannam M, Yokokawa M, Liang JJ, Cochet H, ... Morady F, Bogun F
Heart Rhythm: 30 Dec 2020; 18:20-26 | PMID: 32721479
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Abstract

The rationale for repurposing funny current inhibition for management of ventricular arrhythmia.

Chakraborty P, Rose RA, Nair K, Downar E, Nanthakumar K

Management of ventricular arrhythmia in structural heart disease is complicated by the toxicity of the limited antiarrhythmic options available. In others, proarrhythmia and deleterious hemodynamic and noncardiac effects prevent practical use. This necessitates new thinking in therapeutic agents for ventricular arrhythmia in structural heart disease. Ivabradine, a funny current (I) inhibitor, has proven safety in heart failure, angina, and inappropriate sinus tachycardia. Although it is commonly known that funny channels are primarily expressed in the sinoatrial node, atrioventricular node, and conducting system of the ventricle, ivabradine is known to exert effects on metabolism, ion homeostasis, and membrane electrophysiology of remodeled ventricular myocardium. This review considers novel concepts and evidence from clinical and experimental studies regarding this paradigm, with a potential role of ivabradine in ventricular arrhythmia.

Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Heart Rhythm: 30 Dec 2020; 18:130-137
Chakraborty P, Rose RA, Nair K, Downar E, Nanthakumar K
Heart Rhythm: 30 Dec 2020; 18:130-137 | PMID: 32738405
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Abstract

Is competitive atrial pacing a possible trigger for atrial fibrillation? Observations from the RATE registry.

Orlov MV, Olshansky B, Benditt DG, Kotler G, ... Poghosyan H, Waldo AL
Background
A high incidence of asymptomatic atrial tachycardia and atrial fibrillation (AT/AF) has been recognized in patients with cardiac implantable devices (CIED). The clinical significance of these AT/AF episodes remains unclear. Some \"device-detected AT/AF\" was previously shown to be triggered by competitive atrial pacing (CAP).
Objective
To investigate and characterize a potential association between CAP and AT/AF in the largest series of observations to date.
Methods
RATE, a multicenter registry, included 5379 patients with CIEDs followed for approximately 2 years. Electrograms (EGMs) from 1352 patients with AT/AF, CAP, or both were analyzed by experienced adjudicators to assess a causal relationship between AT/AF and CAP onset, duration, and morphology.
Results
In 225 patients, 1394 episodes of both AT/AF and CAP were present in the same tracing. CAP and AT/AF were strongly associated (P ≤ .02). AT/AF occurred during the course of the study in 71% of patients with CAP. In 62% of the episodes, expert adjudication concluded that CAP triggered AT/AF. The duration and morphology of triggered and spontaneous AT/AF episodes differed. Spontaneous AT/AF episodes were associated with constant EGM morphology, and were either long or extremely short. CAP-triggered AT/AF more often had variable and shorter cycle length EGMs. The incidence of short AT/AF events was higher among triggered episodes (25% vs 12.8%, P < .002).
Conclusion
Device-triggered AT/AF due to CAP is likely more common than previously recognized. This AT/AF entity differs from spontaneous AT/AF in duration and morphology. Clinical implications of spontaneous and device-triggered AT/AF may be different.

Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Heart Rhythm: 30 Dec 2020; 18:3-9
Orlov MV, Olshansky B, Benditt DG, Kotler G, ... Poghosyan H, Waldo AL
Heart Rhythm: 30 Dec 2020; 18:3-9 | PMID: 32738404
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Abstract

Premature ventricular complex site of origin and ablation outcomes in patients with prior myocardial infarction.

Penela D, Teres C, Fernández-Armenta J, Aguinaga L, ... Mont L, Berruezo A
Background
Frequent premature ventricular complexes (PVCs) are common after a myocardial infarction (MI), but data on PVC ablation in this population are limited.
Objective
The purpose of this study was to analyze data on PVC ablation in post-MI patients.
Methods
Three hundred thirty-two patients with frequent PVCs and left ventricular (LV) dysfunction were prospectively studied. Data from 67 patients (20%; age 63 ± 10 years; 65 men [93%]) with previous MI were compared with the remaining 265 patients.
Results
PVCs in post-MI patients originate predominantly from the LV (92% LV vs 6% right ventricle [RV]; P <.001). The most frequent sites of origin (SOO) were MI scar in 23 patients (34%) and left ventricular outflow tract (LVOT) in 22 patients (33%). A papillary muscle origin was more frequent in post-MI patients (16% vs 4%; P = .001), whereas an RV outflow tract origin was less frequent (1% vs 33%; P <.001) compared to patients without MI. In post-MI patients, PVC burden decreased from 29% ± 12% at baseline to 4.6% ± 7% (P <.001); left ventricular ejection fraction (LVEF) improved from 33.6% ± 8% to 42% ± 10% (P <.001); and New York Heart Association functional class improved from 2.1 ± 0.7 to 1.4 ± 0.5 points (P <.001) at 12 months. Compared with the remaining 265 patients, there were no differences in acute ablation success (85% vs 85%; P = .45), complication rate (6% vs 6%; P = .41), or absolute improvement in LVEF (8.8 ± 10 vs 9.9 ± 11 absolute points; P = .38).
Conclusion
PVC ablation significantly improves cardiac function and functional status in post-MI patients. PVCs predominantly originate from MI scar and LVOT. A papillary muscle SOO was found to be strongly associated with previous MI.

Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Heart Rhythm: 30 Dec 2020; 18:27-33
Penela D, Teres C, Fernández-Armenta J, Aguinaga L, ... Mont L, Berruezo A
Heart Rhythm: 30 Dec 2020; 18:27-33 | PMID: 32763430
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Abstract

Simultaneous activation of the small conductance calcium-activated potassium current by acetylcholine and inhibition of sodium current by ajmaline cause J-wave syndrome in Langendorff-perfused rabbit ventricles.

Fei YD, Chen M, Guo S, Ueoka A, ... Weiss JN, Chen PS
Background
Concomitant apamin-sensitive small conductance calcium-activated potassium current (I) activation and sodium current inhibition induce J-wave syndrome (JWS) in rabbit hearts. Sudden death in JWS occurs predominantly in men at night when parasympathetic tone is strong.
Objective
The purpose of this study was to test the hypotheses that acetylcholine (ACh), the parasympathetic transmitter, activates I and causes JWS in the presence of ajmaline.
Methods
We performed optical mapping in Langendorff-perfused rabbit hearts and whole-cell voltage clamp to determine I in isolated ventricular cardiomyocytes.
Results
ACh (1 μM) + ajmaline (2 μM) induced J-point elevations in all (6 male and 6 female) hearts from 0.01± 0.01 to 0.31 ± 0.05 mV (P<.001), which were reduced by apamin (specific I inhibitor, 100 nM) to 0.14 ± 0.02 mV (P<.001). More J-point elevation was noted in male than in female hearts (P=.037). Patch clamp studies showed that ACh significantly (P<.001) activated I in isolated male but not in female ventricular myocytes (n=8). Optical mapping studies showed that ACh induced action potential duration (APD) heterogeneity, which was more significant in right than in left ventricles. Apamin in the presence of ACh prolonged both APD at the level of 25% (P<.001) and APD at the level of 80% (P<.001) and attenuated APD heterogeneity. Ajmaline further increased APD heterogeneity induced by ACh. Ventricular arrhythmias were induced in 6 of 6 male and 1 of 6 female hearts (P=.015) in the presence of ACh and ajmaline, which was significantly suppressed by apamin in the former.
Conclusion
ACh activates ventricular I. ACh and ajmaline induce JWS and facilitate the induction of ventricular arrhythmias more in male than in female ventricles.

Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Heart Rhythm: 30 Dec 2020; 18:98-108
Fei YD, Chen M, Guo S, Ueoka A, ... Weiss JN, Chen PS
Heart Rhythm: 30 Dec 2020; 18:98-108 | PMID: 32763429
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Abstract

Optical capture and defibrillation in rats with monocrotaline-induced myocardial fibrosis 1 year after a single intravenous injection of adeno-associated virus channelrhodopsin-2.

Li J, Wang L, Luo J, Li H, ... Wang X, Huang C
Background
Optogenetics uses light to regulate cardiac rhythms and terminate malignant arrhythmias.
Objective
The purpose of this study was to investigate the long-term validity of optical capture properties based on virus-transfected channelrhodopsin-2 (ChR2) and evaluate the effects of optogenetic-based defibrillation in an in vivo rat model of myocardial fibrosis enhanced by monocrotaline (MCT).
Methods
Fifteen infant rats received jugular vein injection of adeno-associated virus (AAV). After 8 weeks, 5 rats were randomly selected to verify the effectiveness ChR2 transfection. The remaining rats were administered MCT at 11 months. Four weeks after MCT, the availability of 473-nm blue light to capture heart rhythm in these rats was verified again. Ventricular tachycardia (VT) and ventricular fibrillation (VF) were induced by burst stimulation on the basis of enhanced myocardial fibrosis, and the termination effects of the optical manipulation were tested.
Results
Eight weeks after AAV injection, there was ChR2 expression throughout the ventricular myocardium as reflected by both fluorescence imaging and optical pacing. Four weeks after MCT, significant myocardial fibrosis was achieved. Light could still trigger the corresponding ectopic heart rhythm, and the pulse width and illumination area could affect the light capture rate. VT/VF was induced successfully in 1-year-observation rats, and the rate of termination of VT/VF under light was much higher than that of spontaneous termination.
Conclusion
Viral ChR2 transfection can play a long-term role in the rat heart, and light can successfully regulate heart rhythm and defibrillate after cardiac fibrosis.

Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Heart Rhythm: 30 Dec 2020; 18:109-117
Li J, Wang L, Luo J, Li H, ... Wang X, Huang C
Heart Rhythm: 30 Dec 2020; 18:109-117 | PMID: 32781160
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Impact:
Abstract

Impact of preoperative electrophysiological intervention on occurrence of peri/postoperative supraventricular tachycardia following Fontan surgery.

Takeuchi D, Toyohara K, Kudo Y, Nishimura T, Shoda M
Background
Little is known about the effects of preoperative electrophysiological study (EPS) and catheter ablation (CA) in Fontan surgery candidates with supraventricular tachycardia (SVT).
Objective
The purpose of this study was to investigate the clinical impact of EPS-guided intervention in Fontan surgery candidates with preceding SVT events.
Methods
A total of 109 consecutive patients with a history of SVT before Fontan surgery were divided into 3 groups: 44 in whom EPS with CA was attempted (CA group); 21 in whom EPS without CA was attempted (EPS group); and 44 in whom EPS was not performed (N group). The incidence and diagnosis of SVT, acute success rate of CA, and risk factors of peri/postoperative SVT were retrospectively investigated.
Results
The total incidence of SVT within 1 year after Fontan surgery was 34% (n = 37), with 91% of cases occurring within 1 month. Among the 71 SVT incidences diagnosed with EPS, 31 were atrioventricular reentrant tachycardias (AVRTs) involving twin atrioventricular nodes, 12 were atrioventricular nodal reentrant tachycardias, 12 were atrial tachycardias, 7 were orthodromic AVRTs via the accessory pathway, 7 were atrial flutters, and 2 were junctional tachycardias. The acute success rate of CA was 91% (48/53). The rate of peri/postoperative atrioventricular reciprocating SVT was significantly lower in the CA group than in the N or EPS group (11% vs 43% or 43%; P <.05). No/unsuccessful CA significantly increased the risk of peri/postoperative SVT in multivariate analysis (odds ratio 4.43; 95% confidence interval 1.69-11.59).
Conclusion
Preoperative CA reduces peri/postoperative SVT occurrence in Fontan surgery candidates at high risk for SVT.

Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Heart Rhythm: 30 Dec 2020; 18:34-40
Takeuchi D, Toyohara K, Kudo Y, Nishimura T, Shoda M
Heart Rhythm: 30 Dec 2020; 18:34-40 | PMID: 32781159
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Impact:
Abstract

Global electrical heterogeneity associated with drug-induced torsades de pointes.

Stabenau HF, Shen C, Zimetbaum P, Buxton AE, Tereshchenko LG, Waks JW
Background
Drugs belonging to diverse therapeutic classes can prolong myocardial refractoriness or slow conduction. These drugs may be effective and well-tolerated, but the risk of sudden cardiac death from torsades de pointes (TdP) remains a major concern. The corrected QT interval has significant limitations when used for risk stratification. Measurement of global electrical heterogeneity (GEH) could help identify the substrate vulnerable to drug-induced ventricular arrhythmias.
Objective
The purpose of this study was to improve risk stratification for drug-induced TdP by measuring GEH on the electrocardiogram (ECG).
Methods
We analyzed ECG data from a case-control study of patients with a history of drug-induced TdP as well as age- and sex-matched controls. Vectorcardiograms were constructed from ECGs. GEH was measured via the spatial ventricular gradient (SVG) vector (magnitude, azimuth, and elevation). Log odds coefficients for TdP were estimated using multivariable logistic regression.
Results
Among 17 cases (47% male; age 58.9 ± 12.5 years) and 17 controls (29% male; age 61.0 ± 12.2 years), 34 ECGs were analyzed. SVG azimuth was significantly different between cases and controls (3.4 vs 22.0 degrees, respectively; P = 0.02). After adjusting for sex and QTc interval, odds of TdP increased by a factor of 3.2 for each 1 SD change in SVG azimuth from the control group mean (95% confidence interval 1.07-9.14; P = .04). QTc was not significant in the multivariable analysis (P = .20).
Conclusion
SVG azimuth is correlated with a history of drug-induced TdP independent of QTc. GEH measurement may help identify patients at high risk for drug-induced arrhythmias.

Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Heart Rhythm: 30 Dec 2020; 18:57-62
Stabenau HF, Shen C, Zimetbaum P, Buxton AE, Tereshchenko LG, Waks JW
Heart Rhythm: 30 Dec 2020; 18:57-62 | PMID: 32781158
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Impact:
Abstract

Primary prevention implantable cardioverter-defibrillators in hypertrophic cardiomyopathy-Are there predictors of appropriate therapy?

Weissler-Snir A, Dorian P, Rakowski H, Care M, Spears D
Background
Identifying patients with hypertrophic cardiomyopathy (HCM) who warrant a primary prevention implantable cardioverter-defibrillator (ICD) is crucial. ICDs are effective in terminating life-threatening arrhythmias; however, ICDs carry risks of complications.
Objective
The purpose of this study was to assess the incidence and predictors of appropriate ICD therapies, inappropriate shocks, and device-related complications in patients with HCM and primary prevention ICDs.
Methods
All patients with HCM who underwent primary prevention ICD implantation at Toronto General Hospital between September 2000 and December 2017 were identified. Therapies (shocks or antitachycardia pacing) for ventricular tachycardia >180 beats/min or ventricular fibrillation were considered appropriate.
Results
Three hundred two patients were followed for a mean 6.1 ± 4.3 years (1801 patient-years of follow-up). Thirty-eight patients (12.6%) received at least 1 appropriate ICD therapy (2.3%/y); the 5-year cumulative probability of receiving appropriate ICD therapy was 9.6%. None of the conventional risk factors nor the European Society of Cardiology risk score was associated with appropriate ICD therapy. In multivariable analysis, age < 40 years at implantation and atrial fibrillation were independent predictors of appropriate ICD therapy. In a subgroup of patients who had undergone cardiac magnetic resonance imaging before ICD implantation, severe late gadolinium enhancement was the strongest predictor of appropriate ICD therapies. ICD-related complications or inappropriate shocks occurred in 87 patients (28.8%), with an inappropriate shock rate of 2.1%/y; the 5-year cumulative probability was 10.7%.
Conclusion
The incidence of appropriate ICD therapies in patients with HCM and primary prevention ICDs is lower than previously reported; a high proportion of patients suffer from an ICD-related complication. Traditional risk factors have low predictive utility. Severe late gadolinium enhancement, atrial fibrillation, and young age are important predictors of ventricular tachyarrhythmias in HCM.

Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Heart Rhythm: 30 Dec 2020; 18:63-70
Weissler-Snir A, Dorian P, Rakowski H, Care M, Spears D
Heart Rhythm: 30 Dec 2020; 18:63-70 | PMID: 32800967
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Impact:
Abstract

Unexpected high failure rate of a specific MicroPort/LivaNova/Sorin pacing lead.

Haeberlin A, Anwander MT, Kueffer T, Tholl M, ... Roten L, Noti F
Background
Pacing leads are the Achilles heel of pacemakers. Most manufacturers report a 3-year survival rate of >99% of their leads. We observed several failures of the Beflex/Vega leads (MicroPort, Shanghai, China; formerly Sorin/LivaNova).
Objective
The purpose of this study was to investigate failure rates of Beflex/Vega leads.
Methods
We analyzed the performance of Beflex/Vega leads implanted at our tertiary referral center. All-cause lead failures (any issues requiring reinterventions such as lead dislocations, cardiac perforations, and electrical abnormalities) were identified during follow-up. The Beflex/Vega lead was compared with a reference lead (CapSureFix Novus 5076, Medtronic, Minneapolis, MN) implanted within the same period and by the same operators.
Results
A total of 585 leads were analyzed (382 Beflex/Vega and 203 CapSureFix Novus 5076 leads). Cumulative failure rate estimates were 5.2%, 6.3%, and 12.4% after 1, 2, and 3 years for the Beflex/Vega lead. This was worse compared to the reference lead (1.5%, 1.5%, 3.7% after 1, 2, and 3 years; P = .001). Early failure manifestations up to 3 months occurred at a similar rate (Beflex/Vega vs CapSureFix Novus 5076 lead: 1.3% vs 0.5% for dislocations; 1.3% vs 1.0% for perforations). During follow-up, electrical abnormalities such as noise oversensing (P = .013) and increased pacing thresholds (P = .003) became more frequent in the Beflex/Vega group. Electrical abnormalities were the most common failure manifestation 3 years after implantation in this group (9.4% vs 2.2% for the CapSureFix Novus 5076).
Conclusion
The failure rate of the Beflex/Vega lead of >10% after 3 years was higher than that of a competitor lead. This gives rise to concern since >135,000 such leads are active worldwide.

Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Heart Rhythm: 30 Dec 2020; 18:41-49
Haeberlin A, Anwander MT, Kueffer T, Tholl M, ... Roten L, Noti F
Heart Rhythm: 30 Dec 2020; 18:41-49 | PMID: 32798776
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Impact:
Abstract

Risk of arrhythmic events after alcohol septal ablation for hypertrophic cardiomyopathy using continuous implantable cardiac monitoring.

Bleszynski PA, Goldenberg I, Fernandez G, Howell E, ... Cove C, Aktas MK
Background
Alcohol septal ablation (ASA) in patients with hypertrophic cardiomyopathy (HCM) can lead to heart rhythm disturbances including complete heart block (CHB) and atrial and ventricular arrhythmias.
Objective
We aimed to evaluate the utility of long-term arrhythmia monitoring with an implantable cardiac monitor (ICM) after ASA.
Methods
Between February 2014 and March 2019, 56 patients with HCM undergoing ASA were enrolled in a prospective study and underwent ICM implantation. Kaplan-Meier survival analysis was used to assess the rate of ICM-detected arrhythmic events.
Results
The mean age was 59 ± 11 years, and 20 (36%) were women. The median (25th, 75th percentile) resting left ventricular outflow tract gradient obtained by echocardiography was 43 (22, 81) mm Hg. Greater than 1 septal perforating artery was injected in 48 patients (86%). The Kaplan-Meier cumulative rate of ICM-detected arrhythmic events at 18 months of follow-up was 71%, with an event rate of 43% occurring within 3 months of ASA. The cumulative rate of the ICM-detected first atrial fibrillation event at 18 months was 37%, and the corresponding rate of CHB was 19%. All atrial fibrillation and CHB events were actionable, leading to the initiation of anticoagulation and pacemaker implantation, respectively. No baseline demographic or procedural variables were identified as independent predictors of an increased risk of developing ICM-detected arrhythmic events.
Conclusion
After ASA, ICM is effective in capturing clinically actionable arrhythmic events in patients with HCM regardless of patient\'s baseline risk factors.

Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Heart Rhythm: 30 Dec 2020; 18:50-56
Bleszynski PA, Goldenberg I, Fernandez G, Howell E, ... Cove C, Aktas MK
Heart Rhythm: 30 Dec 2020; 18:50-56 | PMID: 32853778
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Abstract

N-terminal pro-B-type natriuretic peptide is a specific predictor of appropriate device therapies in patients with primary prevention implantable cardioverter-defibrillators.

Sroubek J, Matos J, Locke A, Kaplinskiy V, ... Shen C, Buxton AE
Background
Sudden death risk stratification of patients with left ventricular systolic dysfunction remains challenging. Retrospective studies have suggested N-terminal pro-B-type natriuretic peptide (NT-proBNP) may be a useful risk stratification tool.
Objective
The purpose of this study was to ascertain the utility of NT-proBNP as a predictor of appropriate implantable cardioverter-defibrillator (ICD) therapies in primary prevention ICD recipients.
Methods
This was a prospective study of 342 stable patients with left ventricular ejection fraction ≤40% who received a primary prevention ICD. NT-proBNP assay was performed at the time of device implant and used as a dichotomized variable (1st-3rd NT-proBNP quartiles vs 4th NT-proBNP quartile) to predict primary (appropriate ICD therapies) and secondary (death, ICD-deactivation, chronic inotropic support, transplant) outcomes.
Results
Median follow-up was 35.0 months (interquartile range 15.2-55.3). In unadjusted analyses, NT-proBNP predicted both primary (hazard ratio [HR] 1.89; 95% confidence interval [CI] 1.00-3.56); P = .049) and secondary outcomes (HR 2.13; 95% CI 1.18-3.85; P =.012). Multivariable analysis reaffirmed NT-proBNP as a primary outcome predictor (HR 4.31; 95% CI 1.92-9.70; P <.001) but not as a secondary outcome predictor (HR 1.23; 95% CI 0.61-2.50; P = .564). Instead, secondary outcome was predicted by patient age and renal function. In an unadjusted subanalysis limited to patients with blood urea nitrogen <30 mg/dL, NT-proBNP remained a primary endpoint predictor (HR 2.51; 95% CI 1.25-5.05; P = .010) but not a secondary endpoint predictor (HR 1.34; 95% CI 0.52-3.44; P = .541). Receiver operating analyses at 2- and 3-year follow-up timepoints confirmed that NT-proBNP significantly improved the performance of multivariable models designed to predict future appropriate ICD therapies.
Conclusion
In multivariable analysis, NT-proBNP is a reasonable and specific predictor of future appropriate device therapies in primary prevention ICD recipients. In contrast, adjusted NT-proBNP does not predict all-cause mortality.

Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Heart Rhythm: 30 Dec 2020; 18:71-78
Sroubek J, Matos J, Locke A, Kaplinskiy V, ... Shen C, Buxton AE
Heart Rhythm: 30 Dec 2020; 18:71-78 | PMID: 32866691
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Impact:
Abstract

Computer versus cardiologist: Is a machine learning algorithm able to outperform an expert in diagnosing a phospholamban p.Arg14del mutation on the electrocardiogram?

Bleijendaal H, Ramos LA, Lopes RR, Verstraelen TE, ... Wilde AAM, Pinto YM
Background
Phospholamban (PLN) p.Arg14del mutation carriers are known to develop dilated and/or arrhythmogenic cardiomyopathy, and typical electrocardiographic (ECG) features have been identified for diagnosis. Machine learning is a powerful tool used in ECG analysis and has shown to outperform cardiologists.
Objectives
We aimed to develop machine learning and deep learning models to diagnose PLN p.Arg14del cardiomyopathy using ECGs and evaluate their accuracy compared to an expert cardiologist.
Methods
We included 155 adult PLN mutation carriers and 155 age- and sex-matched control subjects. Twenty-one PLN mutation carriers (13.4%) were classified as symptomatic (symptoms of heart failure or malignant ventricular arrhythmias). The data set was split into training and testing sets using 4-fold cross-validation. Multiple models were developed to discriminate between PLN mutation carriers and control subjects. For comparison, expert cardiologists classified the same data set. The best performing models were validated using an external PLN p.Arg14del mutation carrier data set from Murcia, Spain (n = 50). We applied occlusion maps to visualize the most contributing ECG regions.
Results
In terms of specificity, expert cardiologists (0.99) outperformed all models (range 0.53-0.81). In terms of accuracy and sensitivity, experts (0.28 and 0.64) were outperformed by all models (sensitivity range 0.65-0.81). T-wave morphology was most important for classification of PLN p.Arg14del carriers. External validation showed comparable results, with the best model outperforming experts.
Conclusion
This study shows that machine learning can outperform experienced cardiologists in the diagnosis of PLN p.Arg14del cardiomyopathy and suggests that the shape of the T wave is of added importance to this diagnosis.

Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Heart Rhythm: 30 Dec 2020; 18:79-87
Bleijendaal H, Ramos LA, Lopes RR, Verstraelen TE, ... Wilde AAM, Pinto YM
Heart Rhythm: 30 Dec 2020; 18:79-87 | PMID: 32911053
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Impact:
Abstract

Electrical and structural remodeling contribute to atrial fibrillation in type 2 diabetic db/db mice.

Bohne LJ, Jansen HJ, Daniel I, Dorey TW, ... Ezeani M, Rose RA
Background
Atrial fibrillation (AF) is highly prevalent in diabetes mellitus (DM), yet the basis for this finding is poorly understood. Type 2 DM may be associated with unique patterns of atrial electrical and structural remodeling; however, this has not been investigated in detail.
Objective
The purpose of this study was to investigate AF susceptibility and atrial electrical and structural remodeling in type 2 diabetic db/db mice.
Methods
AF susceptibility and atrial function were assessed in male and female db/db mice and age-matched wildtype littermates. Electrophysiological studies were conducted in vivo using intracardiac electrophysiology and programmed stimulation. Atrial electrophysiology was also investigated in isolated atrial preparations using high-resolution optical mapping and in isolated atrial myocytes using patch-clamping. Molecular biology studies were performed using quantitative polymerase chain reaction and western blotting. Atrial fibrosis was assessed using histology.
Results
db/db mice were highly susceptible to AF in association with reduced atrial conduction velocity, action potential duration prolongation, and increased heterogeneity in repolarization in left and right atria. In db/db mice, atrial K currents, including the transient outward current (I) and the ultrarapid delayed rectifier current (I), were reduced. The reduction in I occurred in association with reductions in Kcnd2 mRNA expression and K4.2 protein levels. The reduction in I was not related to gene or protein expression changes. Interstitial atrial fibrosis was increased in db/db mice.
Conclusion
Our study demonstrates that increased susceptibility to AF in db/db mice occurs in association with impaired electrical conduction as well as electrical and structural remodeling of the atria.

Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Heart Rhythm: 30 Dec 2020; 18:118-129
Bohne LJ, Jansen HJ, Daniel I, Dorey TW, ... Ezeani M, Rose RA
Heart Rhythm: 30 Dec 2020; 18:118-129 | PMID: 32911049
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Impact:
Abstract

2020 APHRS/HRS expert consensus statement on the investigation of decedents with sudden unexplained death and patients with sudden cardiac arrest, and of their families.

Stiles MK, Wilde AAM, Abrams DJ, Ackerman MJ, ... Tfelt-Hansen J, Wang DW

This international multidisciplinary document intends to provide clinicians with evidence-based practical patient-centered recommendations for evaluating patients and decedents with (aborted) sudden cardiac arrest and their families. The document includes a framework for the investigation of the family allowing steps to be taken, should an inherited condition be found, to minimize further events in affected relatives. Integral to the process is counseling of the patients and families, not only because of the emotionally charged subject, but because finding (or not finding) the cause of the arrest may influence management of family members. The formation of multidisciplinary teams is essential to provide a complete service to the patients and their families, and the varied expertise of the writing committee was formulated to reflect this need. The document sections were divided up and drafted by the writing committee members according to their expertise. The recommendations represent the consensus opinion of the entire writing committee, graded by Class of Recommendation and Level of Evidence. The recommendations were opened for public comment and reviewed by the relevant scientific and clinical document committees of the Asia Pacific Heart Rhythm Society (APHRS) and the Heart Rhythm Society (HRS); the document underwent external review and endorsement by the partner and collaborating societies. While the recommendations are for optimal care, it is recognized that not all resources will be available to all clinicians. Nevertheless, this document articulates the evaluation that the clinician should aspire to provide for patients with sudden cardiac arrest, decedents with sudden unexplained death, and their families.

Copyright © 2020. Published by Elsevier Inc.

Heart Rhythm: 30 Dec 2020; 18:e1-e50
Stiles MK, Wilde AAM, Abrams DJ, Ackerman MJ, ... Tfelt-Hansen J, Wang DW
Heart Rhythm: 30 Dec 2020; 18:e1-e50 | PMID: 33091602
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Impact:
Abstract

The Decrease in Peak Atrial Longitudinal Strain in Patients with Atrial Fibrillation as a Practical Parameter for Stroke Risk Stratification.

Liao JN, Chao TF, Hung CL, Chen SA
Background
Decreased peak atrial longitudinal strain (LA strain) derived from two-dimensional speckle tracking is frequently observed in patients with atrial fibrillation (AF) and associated with the risk of ischemic stroke.
Objective
We aimed to study the predictive power of the decrease in LA strain in AF population and hypothesize that the difference in LA strain between reference values could be used in a stratified way for prognostication.
Methods
Echocardiography examination was performed using the GE system. The standard score of LA strain (ZLA) was calculated, and patients were classified into five groups: Z0 (0 to -1), Z-1 (-1 to -2), Z-2 (-2 to -3), Z-3, (-3 to -4), and Z-4 (≤-4). The clinical end point was an ischemic stroke.
Results
Among 1,364 subjects with AF (71.4 ± 12.1 years; 55.6%, men), 105 encountered ischemic strokes during a mean follow-up duration of 3.1 ± 1.6 years. No patients in the Z0 and Z-1 groups encountered ischemic stroke. The Kaplan-Meier analysis showed higher rates of stroke in worse ZLA groups. Compared with the Z-2 group, a significantly increased risk of stroke was found in the Z-3 (hazard ratio [HR], 3.697; 95% confidence interval [CI], 1.966-6.951; p < 0.001) and Z-4 (HR, 6.447; 95% CI, 2.990-13.904; p < 0.001) groups in univariate Cox regression analysis. The results remained consistent after multivariate Cox regression analysis.
Conclusion
The decrease of LA strain could be applied in a stratified manner and is significantly associated with the risk of stroke independent from baseline covariates.

Copyright © 2020. Published by Elsevier Inc.

Heart Rhythm: 28 Dec 2020; epub ahead of print
Liao JN, Chao TF, Hung CL, Chen SA
Heart Rhythm: 28 Dec 2020; epub ahead of print | PMID: 33385571
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Impact:
Abstract

High-Intensity Ultrasound Catheter Ablation Achieves Deep, Mid-Myocardial Lesions In-Vivo.

Nazer B, Giraud D, Zhao Y, Hodovan J, ... Gerstenfeld EP, Lindner JR
Background
Radiofrequency (RF) ablation of epicardial and mid-myocardial ventricular arrhythmias (VAs) is limited by lesion depth.
Objectives
To generate deep, mid-interventricular septal (IVS) lesions using high-intensity ultrasound (US) from an endocardial catheter-based approach.
Methods
Irrigated US catheters (12 Fr) were fabricated with 3x5 mm transducers of 5.0, 6.5 and 8.0 MHz frequencies, and compared in an ex vivo perfused myocardial ablation model. In vivo septal ablation in swine (n=12) was performed via femoral venous access to the right ventricle. Lesions were characterized by echocardiography, cardiac MRI and electroanatomic voltage mapping pre- and post-ablation, and at 30 days. Four animals were euthanized immediately post-ablation to compare acute and chronic lesion histology and gross pathology.
Results
In ex vivo models, maximal lesion depth and volume was achieved by 6.5 MHz catheters, which were used in vivo. Lesion depth by gross pathology was similar post-ablation (10.8[95% CI:9.9,12.4] mm) and at 30 days (11.2[CI:10.6,12.4] mm, p=0.56). Lesion volume decreased post-ablation to 30 days (255[CI:198,440] to 162[CI:133,234] mm p=0.05), yet transmurality increased 58%(CI:50,76) to 81%(CI:74,93), attributable to a reduction in IVS thickness (16.0±1.7 to 10.6±2.4 mm, p=0.007). MRI confirmed dense septal ablation by delayed enhancement, with increased T1 time post-ablation and at 30 days, and increased T2 time only post-ablation. Voltage mapping of both sides of IVS demonstrated reduced unipolar (but not bipolar) voltage along the IVS.
Conclusions
High-intensity US catheter ablation may be an effective treatment for mid-myocardial or epicardial VAs from an endocardial approach.

Copyright © 2020. Published by Elsevier Inc.

Heart Rhythm: 28 Dec 2020; epub ahead of print
Nazer B, Giraud D, Zhao Y, Hodovan J, ... Gerstenfeld EP, Lindner JR
Heart Rhythm: 28 Dec 2020; epub ahead of print | PMID: 33385570
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Impact:
Abstract

The Role of Timing in Treatment of Atrial Fibrillation: An AFFIRM Substudy.

Yang E, Tang O, Metkus T, Berger RD, ... Calkins HG, Marine JE
Background
In contrast to historical trials, EAST-AFNET 4 suggests the superiority of early rhythm control compared to rate control in patients with recent-onset atrial fibrillation (AF). The relative contributions of timing versus improvement in AF therapeutics over time is unclear.
Objectives
This study aimed to isolate the assessment of early intervention on AF from temporal changes in AF treatments through a secondary analysis of AFFIRM subjects.
Methods
We compared rate and rhythm control treatments in AFFIRM subjects, stratified by time from their diagnosis of AF. Time-to event analysis was performed to compare all-cause mortality, cardiovascular hospitalizations, stroke, and number of hospitalization days.
Results
Of 4060 AFFIRM subjects, 2526 (62.2%) subjects had their first episode of AF within 6 months of study enrollment. Participants with \"new\" AF had decreased risk for all-cause mortality (p=0.001) compared to those with prior AF diagnoses. Individuals previously diagnosed with AF were similar in age and demographics, but had more medical comorbidities, including myocardial infarction (p=0.006), diabetes mellitus (p=0.002), smoking (p=0.003), and hepatic or renal comorbidities (p=0.008). There were no differences in mortality, cardiovascular hospitalization, or stroke between rate versus rhythm control strategies in either AF subgroup.
Conclusion
AFFIRM subjects diagnosed with atrial fibrillation within 6 months of study enrollment showed no difference in survival, cardiovascular hospitalization, or ischemic stroke between rate and rhythm control strategies. Superiority of rhythm control strategies reported by newer AF trials may be more attributable to the refinement of AF therapies and less related to timing of intervention.

Copyright © 2020. Published by Elsevier Inc.

Heart Rhythm: 27 Dec 2020; epub ahead of print
Yang E, Tang O, Metkus T, Berger RD, ... Calkins HG, Marine JE
Heart Rhythm: 27 Dec 2020; epub ahead of print | PMID: 33383228
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Impact:
Abstract

Marshall bundle elimination, Pulmonary vein isolation, and Line completion for ANatomical ablation of persistent atrial fibrillation (Marshall-PLAN): Prospective, single-center study.

Derval N, Duchateau J, Denis A, Ramirez FD, ... Jaïs P, Pambrun T
Background
Beyond pulmonary vein isolation (PVI), the optimal ablation strategy for persistent atrial fibrillation (AF) remains poorly defined.
Objectives
We sought to examine a novel comprehensive ablation strategy (Marshall-PLAN) strictly based on anatomical considerations.
Methods
Left atrial (LA) sites were sequentially targeted as follows: (1) the coronary sinus and vein of Marshall (CS-VOM) musculature; (2) PVI; and (3) anatomical isthmuses (mitral, roof, and cavotricuspid isthmus [CTI]). The primary endpoint was 12-month freedom from AF/atrial tachycardia (AT).
Results
Seventy-five consecutive patients were included (age 61±9 years, 10 females, AF duration 9±11 months, mean LA volume 197±43 mL). VOM ethanol infusion was completed in 69 patients (92%). The full Marshall-PLAN lesion set (VOM, PVI, mitral, roof and CTI with block) was successfully completed in 68 (91%) patients. At 12 months, 54/75 (72%) patients were free from AF/AT after a single procedure (no antiarrhythmic drugs) in the overall cohort. In the subset of patients with a complete Marshall-PLAN lesion set (n=68), the single procedure success rate was 79%. After 1 or 2 procedures, 67/75 patients (89%) remained free from AF/AT (no antiarrhythmic drugs). After 1 or 2 procedures, VOM ethanol infusion was complete in 72/75 patients (96%).
Conclusions
A novel ablation strategy that systematically targets anatomic atrial structures (VOM ethanol infusion, PVI, and prespecified linear lesions) is feasible, safe, and associated with a high rate of freedom from arrhythmia recurrence at 12 months in patients with persistent AF.

Copyright © 2020. Published by Elsevier Inc.

Heart Rhythm: 27 Dec 2020; epub ahead of print
Derval N, Duchateau J, Denis A, Ramirez FD, ... Jaïs P, Pambrun T
Heart Rhythm: 27 Dec 2020; epub ahead of print | PMID: 33383226
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Impact:
Abstract

Close-coupled Pacing to Identify the \'Functional\' Substrate of Ventricular Tachycardia: Long-term Outcomes of the Paced Electrogram Feature Analysis (PEFA) Technique.

Crinion D, Neira V, Al Hamad N, de Leon A, ... Enriquez A, Redfearn D
Background
The conduction delay and block that comprises the critical isthmus of macro-reentrant ventricular tachycardia (VT) is partly \'functional\', in that it only occurs at faster cycle lengths. Close-coupled pacing stresses the myocardium\'s conduction capacity, and may reveal late potentials (LPs) and fractionation. A growing interest has emerged in targeting this functional substrate.
Objective
To assess the feasibility, and efficacy of a functional substrate VT ablation strategy.
Methods
Cases of scar-related VT undergoing their first ablation were recruited. A closely coupled extra-stimulus (VERP + 30 ms) was delivered at the right ventricular apex, while mapping with a high density catheter. Sites of functional impaired conduction exhibited increased EGM duration due to LP\'s/fractionation. The time to last deflection was annotated on an electroanatomic map, readily identifying ablation targets.
Results
A total of 40 patients were recruited, 34 (85%) ischaemic. The median procedure duration was 330 mins (IQR; 300-369), and ablation time was 49.4 mins (IQR; 33.8-48.3). The median functional substrate area was 41.9 cm (IQR: 22.1 - 73.9). It was similarly distributed across bipolar voltage zones. Non-inducibility was achieved in 34/40 (85%). Median follow-up was 711 days (255.5-972.8), during which 35/39 (89.7%) did not have VT recurrence, and 3/39 (7.5%) died. Anti-arrhythmic drugs were continued in 53.8% (21/39).
Conclusion
Functional substrate ablation resulted in high rates of non-inducibility and freedom from VT. Mapping times were increased considerably. Our findings add to the encouraging trend reported by related techniques. Randomised, multi-centre trials are warranted to assess this next phase of VT ablation.

Copyright © 2020. Published by Elsevier Inc.

Heart Rhythm: 26 Dec 2020; epub ahead of print
Crinion D, Neira V, Al Hamad N, de Leon A, ... Enriquez A, Redfearn D
Heart Rhythm: 26 Dec 2020; epub ahead of print | PMID: 33378703
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Impact:
Abstract

Long-term prognosis of women with Brugada syndrome and Electrophysiologic study.

Rodríguez-Mañero M, Jordá P, Hernandez J, Muñoz C, ... Brugada J, Arbelo E
Background
A male predominance in Brugada syndrome (BrS) has been widely reported and scarce information is available in female patients with BrS.
Objective
We aim to investigate the clinical characteristics and long-term prognosis of women with BrS.
Methods
multicentre retrospective study of patients diagnosed with BrS and previous electrophysiological study (EPS).
Results
Among 770 patients, 177 (23%) were females. At presentation, 150 (84.7%) were asymptomatic. Females presented less frequently a type 1ECG pattern (30.5% vs 55.0%;p<0.001), higher rate of family history of SCD (49.7% vs 29.8%;p<0.001) and less sustained ventricular arrhythmias on EPS (8.5% vs 15.1%;p=0.009). Genetic test was performed in 79 females (45% of the sample) being positive in 34 (19%). An ICD was implanted in 48 (27.1%) females. During a mean follow up of 122,17 months (SD±57.28), 5 (2.8%) females experience a cardiovascular event as compared to 42 (7.1%) males (p=0.04). On multivariable analysis, a positive genetic test (18.71; 95% CI 1.82-192.53; p=0.01), and atrial fibrillation (OR 21.12; 95% CI 1.27-350.85; p=0.03) were predictive of arrhythmic events, while ventricular arrhythmias on EPS (neither with 1 or 3 nor 3 extrastimulus) were not.
Conclusion
Women with BrS represent a minor faction among patients with BrS, and although rate of events is low, it does not constitute a risk-free group. Neither clinical risk factors nor EPS predict future arrhythmic events. Only atrial fibrillation and positive genetic test were identified as risk factors for future arrhythmic events.

Copyright © 2020. Published by Elsevier Inc.

Heart Rhythm: 23 Dec 2020; epub ahead of print
Rodríguez-Mañero M, Jordá P, Hernandez J, Muñoz C, ... Brugada J, Arbelo E
Heart Rhythm: 23 Dec 2020; epub ahead of print | PMID: 33359877
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Impact:
Abstract

Fixation beats - a novel marker for reaching the left bundle branch area during deep septal lead implantation.

Jastrzębski M, Kiełbasa G, Moskal P, Bednarek A, ... Rajzer M, Vijayaraman P
Background
One of the challenges of left bundle branch (LBB) pacing is to place the pacing lead deep enough in the septum to reach the LBB area, yet not too deep to avoid perforation.
Objective
We investigated if the occurrence of the ectopic beats of qR/rsR\' morphology in V1 lead (fixation beats) during the lead fixation would predict that the desired intraseptal lead depth was reached, while the lack of fixation beats would indicate too shallow position, and need for more lead rotations.
Methods
Consecutive patients during LBB pacing device implantation were analyzed retrospectively and then prospectively with respect to the occurrence of the fixation beats during each episode of lead rotation. We compared the presence of fixation beats during the lead rotation event directly before the LBB area depth was reached versus during the events before intermediate/unsuccessful positions.
Results
A total of 339 patients and 1278 lead rotation events were analyzed. In the retrospective phase, the fixation beats were observed in 327/339 of final lead positions and in 9/939 of intermediate lead positions (p<0.001). The sensitivity, specificity, positive and negative predictive value of the fixation beats as a marker for reaching the LBB area were 96.4%, 97.3%, 97.3% and 96.5%, respectively. In the prospective, fixation-beats-guided implantation phase, the fixation beats were observed in all patients and only at the LBB capture depth.
Conclusion
Monitoring fixation beats during deep septal lead deployment can facilitate the procedure and possibly increase the safety of lead implantation.

Copyright © 2020. Published by Elsevier Inc.

Heart Rhythm: 23 Dec 2020; epub ahead of print
Jastrzębski M, Kiełbasa G, Moskal P, Bednarek A, ... Rajzer M, Vijayaraman P
Heart Rhythm: 23 Dec 2020; epub ahead of print | PMID: 33359876
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Impact:
Abstract

Systematic Quantification of Histological Ventricular Fibrosis in Isolated Mitral Valve Prolapse and Sudden Cardiac Death.

Han HC, Parsons SA, Curl CL, Teh AW, ... Delbridge LMD, Lim HS
Background
Cardiac fibrosis in mitral valve prolapse (MVP) is implicated in the development of sudden cardiac death (SCD), however, the pattern remains poorly characterized.
Objective
This study aimed to systematically quantify left and right ventricular fibrosis in individuals with isolated MVP and SCD (iMVP-SCD), whereby other potential causes of death are excluded, compared to a control cohort.
Methods
Individuals with iMVP-SCD were identified from the Victorian Institute of Forensic Medicine, Australia and matched for age, sex and body-mass index to control cases with non-cardiac death. Cardiac tissue sections were analyzed to determine collagen deposition in the left ventricular free wall (anterior, lateral and posterior portions), interventricular septum and right ventricle. Within the iMVP-SCD cases, the endocardial-epicardial distribution of fibrosis within the LV was specifically characterized.
Results
There were 17 cases with iMVP-SCD matched 1:1 with 17 controls yielding 149 samples and 1,788 histological regions. The iMVP-SCD group had increased left ventricular (anterior, lateral and posterior; all p<0.001) and interventricular septum fibrosis (p<0.001), but similar amounts of right ventricular fibrosis (p=0.62) compared to controls. In iMVP-SCD, left ventricular fibrosis was significantly higher in the lateral and posterior wall compared to the anterior wall and interventricular septum (all p<0.001). Within the lateral and posterior wall, iMVP-SCD cases had a significant endocardial-to-epicardial gradient of cardiac fibrosis (p<0.01) similar to other known conditions which cause cardiac remodeling.
Conclusion
Our study indicates that non-uniform left ventricular remodeling with both localized and generalized left ventricular fibrosis is important in the pathogenesis of SCD in individuals with MVP.

Copyright © 2020. Published by Elsevier Inc.

Heart Rhythm: 23 Dec 2020; epub ahead of print
Han HC, Parsons SA, Curl CL, Teh AW, ... Delbridge LMD, Lim HS
Heart Rhythm: 23 Dec 2020; epub ahead of print | PMID: 33359875
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Impact:
Abstract

Prior myocarditis and ventricular arrhythmias: the importance of scar pattern.

Casella M, Bergonti M, Narducci ML, Persampieri S, ... Russo AD, Tondo C
Background
multiple studies have already addressed the importance of anteroseptal scar in patients with non-ischemic cardiomyopathy. However, this pattern has never been fully evaluated in patients with prior myocarditis.
Objective
to evaluate if anteroseptal scar is associated with worse outcome in patients with prior myocarditis and how does it affect the efficacy of catheter ablation (CA).
Methods
this is a retrospective study of consecutive patients, with prior myocarditis and arrhythmic presentation. Cardiac magnetic resonance (CMR) and electro-anatomic voltage mapping (EVM) were used to identify the scar pattern. Patients were referred for either CA or escalated antiarrhythmic drugs (AADs). Main outcome was ventricular arrhythmias (VAs) free-survival according to the presence of anteroseptal scar.
Results
a total of 144 consecutive patients with prior myocarditis were included. Mean age was 42.1±14.9 years and 58% were men. Ejection fraction was normal in 73% of patients. Anteroseptal scar was present in 44% of cases. Sixty-one patients (42%) underwent CA. Overall, at two-year follow-up, VA-free survival was 77% in the CA group. After CA, the mean number of AAD each patient took dropped from 1.8 to 0.9/die (p<0.001). The presence of anteroseptal scar was found to be an independent predictor of VA relapse both in patients treated with CA (HR 3.6, 95% CI 1.1-11.4, p=0.03) and in the overall population (HR 2.0, 95% CI 1.2-3.5, p=0.02) .
Conclusions
In patients with prior myocarditis and VA, the presence of anteroseptal scar negatively predicts outcomes irrespective of the treatment strategy.

Copyright © 2020. Published by Elsevier Inc.

Heart Rhythm: 17 Dec 2020; epub ahead of print
Casella M, Bergonti M, Narducci ML, Persampieri S, ... Russo AD, Tondo C
Heart Rhythm: 17 Dec 2020; epub ahead of print | PMID: 33348060
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Impact:
Abstract

Self-reported Physical Activity and Atrial Fibrillation Risk: A Systematic Review and Meta-analysis.

Mishima RS, Verdicchio CV, Noubiap JJ, Ariyaratnam JP, ... Sanders P, Elliott AD
Background
While physical activity (PA) is an important component of cardiovascular disease prevention and treatment, its role in atrial fibrillation (AF) risk is less well established.
Objective
The objective of this study is to systematically summarize the evidence pertaining to the relationship of PA and risk of AF.
Methods
We searched PubMed and Embase databases for prospective cohort studies reporting the risk of AF associated to a specific PA volume until March 2020. From each study, we extracted the risk associated with a given PA level, in comparison with insufficiently active (\'inactive\') individuals. The reported risk was normalized to metabolic equivalent of task-minutes per week (MET-minutes per week). A random-effects meta-analysis was used to compare AF risk between those who met and those who did not meet PA recommendations (450 MET-minutes per week), and a dose-response analysis between the level of PA and the risk of AF was performed.
Results
Fifteen studies reporting data from 1,464,539 individuals (median age 55.3 years, 51.7 % of female) were included. Individuals achieving guideline-recommended level of PA had a significantly lower risk of AF (HR 0.94, 95% CI 0.90-0.97, p=0.001). Dose response analysis showed that PA levels up to 1900 MET-minutes per week were associated with a lower risk of AF, with less certainty beyond that level.
Conclusion
PA at guideline recommended levels and above are associated with a significantly lower AF risk. However, at 2000 MET-minutes per week and beyond, the benefit is less clear.

Copyright © 2020. Published by Elsevier Inc.

Heart Rhythm: 17 Dec 2020; epub ahead of print
Mishima RS, Verdicchio CV, Noubiap JJ, Ariyaratnam JP, ... Sanders P, Elliott AD
Heart Rhythm: 17 Dec 2020; epub ahead of print | PMID: 33348059
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Impact:
Abstract

Percutaneous management of superior vena cava syndrome in patients with cardiovascular implantable electronic devices.

Gabriels J, Chang D, Maytin M, Tadros T, ... Eisenhauer A, Epstein LM
Background
There is no consensus regarding the optimal management of cardiovascular implantable electronic device (CIED)-related superior vena cava (SVC) syndrome.
Objective
We report our experience with transvenous lead extractions (TLEs) in the setting of symptomatic CIED-related SVC syndrome.
Methods
We reviewed all TLEs performed at a high-volume center over a 14-year period and identified cases in which TLE was performed for symptomatic SVC syndrome. Patient characteristics, extraction details, percutaneous management of SVC occlusions, and clinical follow data were analyzed.
Results
Over a 14-year period, more than 1600 TLEs were performed. Of these, 16 patients underwent TLE for symptomatic SVC syndrome. The mean age was 53.1 ± 12.8 years, and 56.3% were men. Thirty-seven leads, with a mean dwell time of 5.8 years (range 2-12 years), were extracted. After extraction, 6 patients (37.5%) received an SVC stent. Balloon angioplasty was performed before stenting in 5 cases (31.3%). There was 1 major complication (6.3%) due to an SVC tear that was managed surgically with a favorable outcome. Eleven patients underwent reimplantation of a CIED. Over a median follow-up of 5.5 years (interquartile range 2.0-8.5 years), 12 patients (75%) remained free of symptoms.
Conclusion
Combining TLE with the percutaneous treatment of symptomatic SVC syndrome is a safe and viable treatment strategy.

Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Heart Rhythm: 16 Dec 2020; epub ahead of print
Gabriels J, Chang D, Maytin M, Tadros T, ... Eisenhauer A, Epstein LM
Heart Rhythm: 16 Dec 2020; epub ahead of print | PMID: 33212249
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Abstract

Identification of two preclinical canine models of atrial fibrillation to facilitate drug discovery.

Freudenberger T, Kranz B, Lehmann W, Schäfer K, ... Ellinor PT, Hucker WJ
Background
Atrial fibrillation (AF) is the most common human arrhythmia with a critical need for new treatment strategies.
Objectives
Since the lack of reliable preclinical animal models of AF is a major limitation to drug development of novel anti-arrhythmic compounds, we sought to provide a comprehensive head-to-head assessment of five canine AF-models.
Methods
Five canine models were evaluated for the efficacy of AF induction and AF duration. We tested two acute models: Short-term atrial tachypacing (AT) for 6 hours with analysis of AF at hourly increments, and carbachol injection into a cardiac fat pad followed by short-term AT. We also tested 3 chronic models: pacemaker implantation followed by either 4 weeks of AT and subsequent atrial burst pacing, or intermittent long-term AT for up to 4-5 months to generate AF ≥ 4.5 hours, and finally ventricular tachypacing to induce heart failure followed by atrial burst pacing to induce AF.
Results
Careful evaluation showed that acute AT, AT for 4 weeks, and the heart failure model all were unsuccessful in generating reproducible AF episodes of sufficient duration to study antiarrhythmic drugs. In contrast, intermittent long-term AT generated AF lasting ≥ 4.5 hours in ∼30% of animals. Finally, the acute model using carbachol and short-term AT resulted in AF induction of ≥ 15 minutes in ≥ 75% of animals, thus enabling testing of antiarrhythmic drugs.
Conclusion
Intermittent long-term AT and the combination of local carbachol injection with successive short-term AT may contribute to future drug development efforts for AF.

Copyright © 2020. Published by Elsevier Inc.

Heart Rhythm: 16 Dec 2020; epub ahead of print
Freudenberger T, Kranz B, Lehmann W, Schäfer K, ... Ellinor PT, Hucker WJ
Heart Rhythm: 16 Dec 2020; epub ahead of print | PMID: 33346136
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Abstract

Catheter Ablation of Ventricular Arrhythmias in Left Ventricular NonCompaction Cardiomyopathy.

Sánchez Muñoz JJ, Esparza CM, Verdú PP, Sánchez JM, ... Gimeno Blanes JR, Alberola AG
Background
There are limited data on ventricular arrhythmias (VA) associated with left ventricular noncompaction (LVNC) cardiomyopathy.
Objectives
This study aims to analyze the clinical and electrocardiographic characteristics of VA in a group of patients with LVNC.
Methods
42 non-related patients with LVNC and VA were included evaluated at the Inherited Cardiac Disease Unit of the University Hospital Virgen Arrixaca (Murcia-Spain) (ERN Guard-Heart Centres. European Reference Network for Rare and Low Prevalence Complex Diseases of the Heart).
Results
Thirteen patients (30.9%) had isolated LVNC, 27 (64.3%) LVNC associated with dilated cardiomyopathy (DCM), 2 (4.8%) with hypertrophic cardiomyopathy (HCM). Among isolated LVNC individuals, 9 (69.2%) had PVC/non-sustained VT , and 4 (30.8%) VT ( 1 VT degenerating in VF) . In the DCM group, 11 (40.7%) patients had premature ventricular contractions (PVC), 14 (51.9%) ventricular tachycardia (VT) and 2 (7.4%) ventricular fibrillation (VF). In the HCM group, one patient had PVC and the other VT. Endocardial mapping and ablation were performed in 19 patients (45.2%): 6 in ventricle outflow tracts (4 RV outflow tract, 1 left coronary cup, 1 right coronary cusp), 2 LV summit, 5 related with Purkinje potentials at the mid inferoseptal area and 5 associated with endocardial scar localized in the basal anterolateral and inferolateral segments. Epicardial ablation was carried out in 3 cases.
Conclusions
The substrate of ventricular arrhythmias in left ventricular noncompaction cardiomyopathy is heterogeneous, with origin in ventricular outflow tracts, Purkinje system related , and resembling scar patterns in nonischemic cardiomyopathy.

Copyright © 2020. Published by Elsevier Inc.

Heart Rhythm: 16 Dec 2020; epub ahead of print
Sánchez Muñoz JJ, Esparza CM, Verdú PP, Sánchez JM, ... Gimeno Blanes JR, Alberola AG
Heart Rhythm: 16 Dec 2020; epub ahead of print | PMID: 33346135
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Abstract

Etiology and prognosis of patients with unexplained syncope and mid-range left ventricular dysfunction.

Francisco-Pascual J, Rodenas E, Rivas-Gándara N, Belahnech Y, ... Maldonado J, Ferreira-González I
Background
Syncope in patients with mid-range LVEF can be due to potentially serious arrhythmic causes. However, there is no clear consensus regarding the best way to manage these patients.
Objectives
Determine the causes of syncope and assess the diagnostic yield and safety of a stepwise work-up protocol in this population.
Methods
Prospective observational study. A stepwise work-up protocol was applied to patients with LVEF 35-50% and unexplained syncope after initial assessment (Step 1).
Results
104 patients were included. (median age 75.6 years [IQR 67.6-81.2 years], median LVEF 45% [IQR 40-48%], median follow-up 2.0 years [IQR 0.7-3.3 years]). In 71 patients (68.3%) a diagnosis was reached, 55 (77,5%) in Step 2 (Hospital admission & electrophysiology study (EPS)) and 16 (36.5%) in Step 3 (implantable cardiac monitor (ICM)). Arrhythmic causes were the most common etiology (45.2% AV block, 9.6% VT). 60 (57.7%) patients required the implantation of a cardiac device, 11 with a defibrillation function. Patients diagnosed in Step 3 had a greater global risk of recurrence of syncope (HR 6.5; 95% CI 2.3-18.0). The mortality rate was 8.1% person-years and the sudden or unknown death rate was 0.9 % person-year.
Conclusions
In patients with mid-range LV dysfunction and syncope of unknown cause, a systematic diagnostic strategy based on EPS and/or ICM implantation allows a diagnosis to be reached in a high proportion of cases and guides the treatment. Arrhythmia is the most common cause of syncope in this population, particularly AV block.

Copyright © 2020. Published by Elsevier Inc.

Heart Rhythm: 12 Dec 2020; epub ahead of print
Francisco-Pascual J, Rodenas E, Rivas-Gándara N, Belahnech Y, ... Maldonado J, Ferreira-González I
Heart Rhythm: 12 Dec 2020; epub ahead of print | PMID: 33326869
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Impact:
Abstract

Twin Atrioventricular Nodes, Arrhythmias and Survival in Pediatric and Adult Patients with Heterotaxy Syndrome.

Wu MH, Wang JK, Chiu SN, Tseng WC, ... Lin MT, Chen CA
Background
Heterotaxy syndrome is likely to involve arrhythmias from associated conduction system abnormalities, which are distinct in different subtypes of isomerism and may change further after interventions and remodeling.
Objective
To understand the risk of arrhythmias and its relation to isomerism subtypes.
Methods
Patients diagnosed between 1980 and 2019 as having heterotaxy syndrome were enrolled and grouped as right (RAI), left (LAI), or indeterminate isomerism.
Results
Of 366 patients enrolled, 326 (89.1%) had RAI, 35 (9.6%) LAI, and 5 (1.4%) indeterminate isomerism; 71 patients were adults. Arrhythmias occurred in 37.2% of patients (109 supraventricular tachycardia, 8 atrial fibrillation/flutter, 12 ventricular tachycardia, and 14 paced bradycardia). Freedom from arrhythmias by age 1, 5, 10, 20, and 40 years was 0.849, 0.680, 0.550, 0.413, and 0.053, respectively. Twin AV nodes were identified in 51.5% of RAI, 8.7% of LAI, and 40.0% of indeterminate isomerism and were the key predictor of supraventricular tachycardia. Indeterminate isomerism was also a risk factor for supraventricular tachycardia. Other forms of tachycardia appeared relatively late. Sinus bradycardia with junctional rhythm was common in LAI (48.7%) and less in indeterminate isomerism (20.0%), with none occurring in RAI. Only in patients with RAI who showed the poorest survival, ventricular tachycardia worsened the long-term survival.
Conclusions
Right atrial isomerism was the predominant subtype of heterotaxy in this cohort. Collectively, the median right/left atrial isomerism ratio was 0.731 and 5.450 in Western and East Asian studies, respectively. Arrhythmias, tachycardia, or paced bradycardia were common, but the spectrum was distinct among subtypes.

Copyright © 2020. Published by Elsevier Inc.

Heart Rhythm: 11 Dec 2020; epub ahead of print
Wu MH, Wang JK, Chiu SN, Tseng WC, ... Lin MT, Chen CA
Heart Rhythm: 11 Dec 2020; epub ahead of print | PMID: 33321198
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Impact:
Abstract

Staphylococcus bacteremia without evidence of a cardiac implantable electronic device infection.

Nakajima I, Narui R, Tokutake K, Norton CA, ... Crossley GH, Montgomery JA
Background
Staphylococcus bacteremia (SB) in the presence of a cardiac implantable electronic device (CIED) is frequently associated with CIED infection. In patients without clear CIED infection but SB, the role for empiric CIED removal is unclear.
Objective
Describe the natural history of SB in the setting of a CIED and the impact of CIED removal on mortality in patients with concurrent SB without evidence of CIED infection.
Methods
Three hundred sixty consecutive patients (61±17 years, 71% male, 92% Staphylococcus aureus) with CIEDs and concurrent SB were reviewed.
Results
At the initial presentation with SB, 178 patients had no evidence of CIED infection. Of these, 132 (74%) had another identified source of infection. Of the 178 patients without CIED infection, 18 (10%) had empiric CIED removal during the initial bacteremia. Among those who did not undergo CIED removal, SB subsequently relapsed in 19% and relapse rates were not different for those with or without another identifiable source at initial presentation. Relapse was strongly associated with duration of SB >1-day (odds ratio, 9.99; 95% confidence interval [CI] 3.24-30.86). Despite absence of CIED infection, one-year mortality was 35% and empiric device removal during the initial presentation was associated with survival benefit (hazard ratio 0.28, 95% CI 0.08-0.95).
Conclusion
For patients with SB without evidence of CIED infection, relapse is predicted by the duration of bacteremia. Empiric CIED removal appears to be associated with a survival benefit, although there are likely clinical situations in which this could be deferred.

Copyright © 2020. Published by Elsevier Inc.

Heart Rhythm: 11 Dec 2020; epub ahead of print
Nakajima I, Narui R, Tokutake K, Norton CA, ... Crossley GH, Montgomery JA
Heart Rhythm: 11 Dec 2020; epub ahead of print | PMID: 33321197
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Impact:
Abstract

Active compression versus standard anterior-posterior defibrillation for external cardioversion of atrial fibrillation: A prospective randomized study.

Squara F, Elbaum C, Garret G, Liprandi L, ... Moceri P, Ferrari E
Background
Electrical cardioversion is the first-line rhythm control therapy for symptomatic persistent atrial fibrillation (AF). Contemporary use of biphasic shock waveforms and anterior-posterior positioning of defibrillation electrodes have improved cardioversion efficacy; however, it remains unsuccessful in >10% of patients.
Objective
The purpose of this study was to assess the efficacy of applying active compression on defibrillation electrodes during AF cardioversion.
Methods
We performed a bicenter randomized study including patients referred for persistent AF cardioversion. Elective external cardioversion was performed by a standardized step-up protocol with increasing biphasic shock energy (50-100-150-200 J). Patients were randomly assigned to standard anterior-posterior defibrillation or to defibrillation with active compression applied over the anterior electrode. If sinus rhythm was not achieved at 200 J, a single crossover shock (200 J) was applied. Defibrillation threshold, total delivered energy, number of shocks, and success rate were compared between groups.
Results
We included 100 patients, 50 in each group. In the active compression group, defibrillation threshold was lower (103.1 ± 49.9 J vs 130.4 ± 47.7 J; P = .008), as well as total delivered energy (203 ± 173.3 J vs 309 ± 213.5 J; P = .0076) and number of shocks (2.2 ± 1.1 vs 2.9 ± 1.2; P = .0033), and cardioversion was more often successful (48 of 50 patients [96%] vs 42 of 50 patients [84%]; P = .0455) than that in the standard anterior-posterior group. Crossover from the compression group to the standard group was not successful (0 of 2 patients), whereas crossover from the standard group to the compression group was successful in 50% of patients (4 of 8).
Conclusion
Active compression applied to the anterior defibrillation electrode is more effective for persistent AF cardioversion than standard anterior-posterior cardioversion, with lower defibrillation threshold and higher success rate.

Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Heart Rhythm: 09 Dec 2020; epub ahead of print
Squara F, Elbaum C, Garret G, Liprandi L, ... Moceri P, Ferrari E
Heart Rhythm: 09 Dec 2020; epub ahead of print | PMID: 33181323
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Impact:
Abstract

3D-GUIDED SELECTIVE RIGHT VENTRICULAR SEPTAL PACING PRESERVES VENTRICULAR SYSTOLIC FUNCTION AND SYNCHRONY IN PAEDIATRIC PATIENTS.

Silvetti MS, Pazzano V, Battipaglia I, Saputo FA, ... Ravà L, Drago F
Background
Non-fluoroscopic 3D-electroanatomic mapping systems (EAMs) have been developed to guide cardiac catheter navigation and reduce fluoroscopy. Selective right ventricular (RV) septal pacing could prevent pacing-induced left ventricular (LV) dysfunction.
Objective
Aim of the study was to seek out if EAM-guided selective RV septal pacing preserves LV contractility/synchrony in pediatric patients with complete atrioventricular block (CAVB) and no other congenital heart defects.
Methods
Prospective analysis of children/adolescents who underwent EAM-guided selective RV pacing. A 3D-pacing map guided ventricular lead implantation in septal sites with narrow paced QRS. Serial echocardiograms were obtained following the pacemaker implantation to monitor for the function (volumes, ejection fraction [EF], global longitudinal/circumferential strain) and synchrony (interventricular mechanical delay, septal to posterior wall mechanical delay, systolic dyssynchrony index). Data are reported as median (25-75 percentile). P<0.05 was significant.
Results
Thirty-two CAVB patients (11 with a previous pacing system), aged 9.8 (7.0-14.0) years, underwent selective RV septal pacing (13 DDD, 19 VVIR pacemakers) in midseptum (22 patients), para-Hisian (7), RV outflow tract (3) with narrow paced QRS [110 (100-120) ms], and low radiation exposure. Follow-up over 24 (5-33) months showed preserved LV function and synchrony, without significant differences between pacing sites (midseptum-paraHisian) and mode (VVIR-DDD). EF decreased after implantation in patients without previous pacing, although values were mainly within normal limits. Three para-Hisian patients underwent early lead repositioning.
Conclusion
EAM-guided selective RV septal pacing is a feasible technique associated with preserved LV systolic function and synchrony and low radiation exposure in pediatric patients with CAVB.

Copyright © 2020. Published by Elsevier Inc.

Heart Rhythm: 06 Dec 2020; epub ahead of print
Silvetti MS, Pazzano V, Battipaglia I, Saputo FA, ... Ravà L, Drago F
Heart Rhythm: 06 Dec 2020; epub ahead of print | PMID: 33307214
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Impact:
Abstract

Prognostic Value of Cardiac Magnetic Resonance Septal Late Gadolinium Enhancement Patterns for Periaortic Ventricular Tachycardia Ablation: Heterogeneity of the Anteroseptal Substrate in Nonischemic Cardiomyopathy.

Nishimura T, Patel HN, Wang S, Upadhyay GA, ... Patel AR, Tung R
Background
Ventricular tachycardia (VT) from the anteroseptal subtype of nonischemic cardiomyopathy has a high probability of recurrence after catheter ablation.
Objective
To determine the predictive value of septal scar patterns by late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) on ablation outcomes in patients with VT arising from anteroseptal substrate.
Methods
Patients with periaortic VT arising from anteroseptal substrate with pre-procedural wideband LGE-CMR were divided into 2 groups by the degree of longitudinal septal LGE extension; full-length septal (≥ 80% antero-posterior length) and partial septal (<80% antero-posterior length). Septal LGE volumes were quantified in those with and without VT recurrence.
Results
Amongst 234 patients referred for scar-related VT ablation between 2017-2020, 25 patients (male: 92%, age: 64 ± 8 yrs) and a total of 108 VTs were analyzed. A greater number of VT morphologies were induced in patients with full-length septal LGE compared to partial septal LGE (5 [3-9] vs. 2 [1-4], p=0.005). Patients with VT recurrence had larger septal LGE volumes compared to those without recurrence (11.4 ml [8.8-13.9 ml] vs. 4.2 ml [0-9.5 ml], p=0.012). At a median follow-up of 16 months (5-22 months), overall freedom from VT recurrence was 52% and significantly higher in patients with partial septal LGE compared to full-length septal LGE (80% vs. 20%, p=0.005).
Conclusion
VT originating from an anteroseptal substrate is associated with heterogeneous patterns and extent of CMR septal scar. Pre-procedural imaging may substratify this challenging patient population for the propensity toward multiple induced VT morphologies and recurrence after catheter ablation.

Copyright © 2020. Published by Elsevier Inc.

Heart Rhythm: 06 Dec 2020; epub ahead of print
Nishimura T, Patel HN, Wang S, Upadhyay GA, ... Patel AR, Tung R
Heart Rhythm: 06 Dec 2020; epub ahead of print | PMID: 33301979
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Abstract

A circadian clock in the sinus node mediates day-night rhythms in Hcn4 and heart rate.

D\'Souza A, Wang Y, Anderson C, Bucchi A, ... DiFrancesco D, Boyett MR
Background
Heart rate follows a diurnal variation, and slow heart rhythms occur primarily at night.
Objective
The lower heart rate during sleep is assumed to be neural in origin, but here we tested whether a day-night difference in intrinsic pacemaking is involved.
Methods
In vivo and in vitro electrocardiographic recordings, vagotomy, transgenics, quantitative polymerase chain reaction, Western blotting, immunohistochemistry, patch clamp, reporter bioluminescence recordings, and chromatin immunoprecipitation were used.
Results
The day-night difference in the average heart rate of mice was independent of fluctuations in average locomotor activity and persisted under pharmacological, surgical, and transgenic interruption of autonomic input to the heart. Spontaneous beating rate of isolated (ie, denervated) sinus node (SN) preparations exhibited a day-night rhythm concomitant with rhythmic messenger RNA expression of ion channels including hyperpolarization activated cyclic nucleotide gated potassium channel 4 (HCN4). In vitro studies demonstrated 24-hour rhythms in the human HCN4 promoter and the corresponding funny current. The day-night heart rate difference in mice was abolished by HCN block, both in vivo and in the isolated SN. Rhythmic expression of canonical circadian clock factors, for example, Bmal1 and Cry, was identified in the SN and disruption of the local clock (by cardiac-specific knockout of Bmal1) abolished the day-night difference in Hcn4 and intrinsic heart rate. Chromatin immunoprecipitation revealed specific BMAL1 binding sites on Hcn4, linking the local clock with intrinsic rate control.
Conclusion
The circadian variation in heart rate involves SN local clock-dependent Hcn4 rhythmicity. Data reveal a novel regulator of heart rate and mechanistic insight into bradycardia during sleep.

Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Heart Rhythm: 02 Dec 2020; epub ahead of print
D'Souza A, Wang Y, Anderson C, Bucchi A, ... DiFrancesco D, Boyett MR
Heart Rhythm: 02 Dec 2020; epub ahead of print | PMID: 33278629
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Abstract

Insulin-Like Growth Factor-Binding Protein-7 and risk of congestive heart failure hospitalization in patients with atrial fibrillation.

Blum S, Aeschbacher S, Meyre P, Kühne M, ... Conen D,
Background
The occurrence of congestive heart failure (CHF) hospitalization among patients with atrial fibrillation (AF) is a poor prognostic marker.
Objective
To assess whether Insulin-Like Growth Factor-Binding Protein-7 (IGFBP-7), a marker of myocardial damage, identifies AF patients at high risk for this complication.
Methods
We analyzed two prospective multicenter observational cohort studies including 3,691 AF patients. Levels of IGFBP-7 and N-terminal pro-brain natriuretic peptide (NT-proBNP) were measured from frozen plasma samples at baseline. The primary endpoint was hospitalization for CHF. Multivariable adjusted Cox-regression analyses were constructed.
Results
Mean age was 69±12 years, 1,028 (28%) were females and 879 (24%) had a history of CHF. The incidence per 1,000 patient-years across increasing IGFBP-7 quartiles was 7, 10, 32 and 85. The corresponding multivariable adjusted hazard ratios (aHRs) [95%CI] were 1.0, 1.05 [0.63;1.77], 2.38 [1.50;3.79], and 4.37 [2.72;7.04] (p for trend <0.001). In a subgroup of 2,812 patients without pre-existing CHF at baseline, the aHRs were 1.0, 0.90 [0.47;1.72], 1.69 [0.94;3.04], and 3.48 [1.94;6.24] (p for trend <0.001). Patients with IGFBP-7 and NT-proBNP levels above the biomarker-specific median had a higher risk of incident CHF hospitalization (aHR 5.20 [3.35; 8.09]) compared to those with only one elevated marker (elevated IGFBP-7 aHR 2.17[1.30;3.60]; elevated NT-proBNP aHR 1.97[1.17;3.33]) or no elevated marker (reference).
Conclusion
Higher plasma levels of IGFBP-7 were strongly and independently associated with CHF hospitalization in AF-patients. The prognostic information provided by IGFBP-7 was additive to that of NT-proBNP.

Copyright © 2020. Published by Elsevier Inc.

Heart Rhythm: 01 Dec 2020; epub ahead of print
Blum S, Aeschbacher S, Meyre P, Kühne M, ... Conen D,
Heart Rhythm: 01 Dec 2020; epub ahead of print | PMID: 33278630
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Abstract

Simultaneous epicardial-endocardial mapping of the sinus node in humans with structural heart disease: Impact of overdrive suppression on sinoatrial exits.

Parameswaran R, Lee G, Morris GM, Royse A, ... Kistler PM, Kalman JM
Background
The 3-dimensional (3D) nature of sinoatrial node (SAN) function has not been characterized in the intact human heart.
Objective
The purpose of this study was to characterize the 3D nature of SAN function in patients with structural heart disease (SHD) using simultaneous endocardial-epicardial (endo-epi) phase mapping.
Methods
Simultaneous intraoperative endo-epi SAN mapping was performed during sinus rhythm at baseline (SR) and postoverdrive suppression at 600 ms (SR) and 400 ms (SR) using 2 Abbott Advisor HD Grid Mapping Catheters. Unipolar and bipolar electrograms (EGMs) were exported for phase analysis to determine (1) activation exits; (2) wavefront propagation sequence; (3) endo-epi dissociation; and (4) fractionation. Comparison of these variables was made among the 3 rhythms from an endo-epi perspective.
Results
Sixteen patients with SHD were included. SR activations were unicentric and predominantly exited cranially (87.5%) with endo-epi synchrony. However, with overdrive suppression, a tendency for caudal exit shift and endo-epi asynchrony was observed: SR vs SR: cranial endo 75% vs 87.5% (P = .046); cranial epi 68.8% vs 87.5% (P = 0.002); caudal endo 12.5% vs 6.2% (P = 0.215); caudal epi 25% vs 6.2% (P = .0003); and SR vs SR: cranial endo 81.3% vs 87.5% (P = 0.335); cranial epi 68.7% vs 87.5% (P = 0.0034; caudal endo 12.5% vs 6.2% (P = .148); caudal epi 31.2% vs 6.2% (P = 0.0017), consistent with multicentricity. EGM fractionation was more prevalent with overdrive suppression.
Conclusion
During mapping of the intact human heart, SAN demonstrated redundancy of sinoatrial exits with postoverdrive shift in sites of earliest activation and epi-endo dissociation of sinoatrial exits.

Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Heart Rhythm: 29 Nov 2020; 17:2154-2163
Parameswaran R, Lee G, Morris GM, Royse A, ... Kistler PM, Kalman JM
Heart Rhythm: 29 Nov 2020; 17:2154-2163 | PMID: 32622994
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Abstract

Safety of leadless pacemaker implantation in the very elderly.

Pagan E, Gabriels J, Khodak A, Chang D, ... Epstein LM, Willner J
Background
The Micra leadless pacemaker (MLP) has proven to be an effective alternative to a traditional transvenous pacemaker (TVP). However, there has been concern about using the MLP in frail elderly patients because of the size of the implant sheath and perceived risk of perforation.
Objectives
The objectives of this study were to report the safety of the MLP and compare MPLs with TVPs in the very elderly.
Methods
All patients 85 years and older who received an MLP or a single-chamber TVP across 6 hospitals in the Northwell Health system from December 2015 to November 2019 were included. Demographic characteristics, procedural details, and procedure-related complications were reviewed.
Results
Over 4 years, 564 patients underwent MLP implantation. During this time, 183 MLPs and 119 TVPs were implanted in patients 85 years and older. The mean age was 89.7 ± 3.4 years, and 47.4% were men. MLP implantation was successful in all but 3 patients (98.4% success rate). There was no difference in procedure-related complications (3.3% vs 5.9%; P = .276). Complications included 5 (2.7%) access site hematomas in the MLP group, 3 (2.5%) in the TVP group, 1 (0.5 vs 0.8%) pericardial effusion in each group, and 3 (2.5%) acute lead dislodgments (<24 hours) in the TVP group. MLP implantation resulted in a significantly shorter mean procedure time (35.7 ± 23.0 minutes vs 62.3 ± 31.5 minutes, P < .001).
Conclusion
In a large multicenter study of patients 85 years and older, MLP implantation (1) was successful in 98.4% of patients, (2) was safe with no difference in procedure-related complications compared to the TVP group, and (3) resulted in significantly shorter procedure times.

Published by Elsevier Inc.

Heart Rhythm: 29 Nov 2020; 17:2023-2028
Pagan E, Gabriels J, Khodak A, Chang D, ... Epstein LM, Willner J
Heart Rhythm: 29 Nov 2020; 17:2023-2028 | PMID: 32454218
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Abstract

Macroreentrant biatrial tachycardia relevant to interatrial septal incisions after mitral valve surgery: Electrophysiological characteristics and ablation strategy.

Zhang J, Hu W, Zhao A, Yang G, ... Su X, Chen M
Background
Macroreentrant biatrial tachycardia (BiAT) associated with interatrial septal incisions after mitral valve (MV) surgery has been rarely reported.
Objective
The purpose of this study was to assess the mapping and ablation strategy of this special category of atrial tachycardia (AT).
Methods
We identified 10 BiATs from a total of 84 ATs after MV surgery performed at 3 institutions. Activation maps for both the right atrium (RA) and left atrium (LA) were obtained using an ultrahigh-density mapping system. We also performed entrainment pacing from multiple LA and RA site within the speculative circuit.
Results
By analyzing activation and propagation maps of both atria, we classified the circuit into 3 distinct types. In all types, posteroinferior interatrial connections act as a critical limb that, combined with other interatrial connections (Bachmann bundle, fossa ovalis, and coronary sinus ostium in 3 types, respectively), complete the circuit of BiATs. Most ATs (8/10) were terminated targeting the RA and LA end of posteroinferior interatrial connection sites.
Conclusion
Ultrahigh-density mapping provides a detailed description of the macroreentrant circuit of BiAT associated with interatrial septal incisions. Posteroinferior interatrial connections were essential for the circuit and should be the preferred target for ablation.

Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Heart Rhythm: 29 Nov 2020; 17:2135-2144
Zhang J, Hu W, Zhao A, Yang G, ... Su X, Chen M
Heart Rhythm: 29 Nov 2020; 17:2135-2144 | PMID: 32619741
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Abstract

Double-balloon technique for retrograde venous ethanol ablation of ventricular arrhythmias in the absence of suitable intramural veins.

Da-Wariboko A, Lador A, Tavares L, Dave AS, ... Papiashvili G, Valderrábano M
Background
Venous ethanol infusion via an occlusive balloon has been used as a bailout approach to treat ablation-refractory ventricular arrhythmias (VAs). Unfavorable venous anatomy (lack of intramural veins at the targeted site or collateral vein-ethanol shunting) limits its efficacy. Blocking collateral flow with a second balloon may optimize myocardial ethanol delivery.
Objective
The purpose of this study was to validate the \"double-balloon\" approach to enhance ethanol delivery in cases of unfavorable venous anatomy.
Methods
Eight patients referred after failed ablations (3 left ventricular [LV] summit, 5 scar-related ventricular tachycardia) underwent endocardial mapping and additional radiofrequency ablation without VA resolution. Coronary veins were mapped using a multipolar catheter or wire, and selective venograms were obtained. The double balloon was used when (1) distal collateral branches shunted flow away from the targeted region; (2) the target vein had optimal signals only proximally; or (3) a large vein was targeted that had multiple branches for a large area of interest.
Results
Acute successful ethanol infusion myocardial delivery and resolution of VA was accomplished using the posterolateral LV veins (n = 2 patients, 3 procedures), lateral LV vein (n = 1), apical anterior interventricular vein (AIV; n = 1), middle cardiac vein (n = 1), and septal branches of the AIV (n = 3). At median follow-up of 313.5 days, 2 patients experienced recurrence.
Conclusion
The double-balloon technique can enhance ethanol delivery to target isolated vein segments, block collateral flow, or target extensive areas, and can expand the utility of venous ethanol for treatment of VAs.

Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Heart Rhythm: 29 Nov 2020; 17:2126-2134
Da-Wariboko A, Lador A, Tavares L, Dave AS, ... Papiashvili G, Valderrábano M
Heart Rhythm: 29 Nov 2020; 17:2126-2134 | PMID: 32470622
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Impact:
Abstract

High-throughput discovery of trafficking-deficient variants in the cardiac potassium channel K11.1.

Kozek KA, Glazer AM, Ng CA, Blackwell D, ... Roden DM, Kroncke BM
Background
KCHN2 encodes the K11.1 potassium channel responsible for I, a major repolarization current during the cardiomyocyte action potential. Variants in KCNH2 that lead to decreased I have been associated with long QT syndrome type 2 (LQT2). The mechanism of LQT2 is most often induced loss of K11.1 trafficking to the cell surface. Accurately discriminating between variants with normal and abnormal trafficking would aid in understanding the deleterious nature of these variants; however, the volume of reported nonsynonymous KCNH2 variants precludes the use of conventional methods for functional study.
Objective
The purpose of this study was to report a high-throughput, multiplexed screening method for KCNH2 genetic variants capable of measuring the cell surface abundance of hundreds of missense variants in the resulting K11.1 channel.
Methods
We developed a method to quantitate K11.1 variant trafficking on a pilot region of 11 residues in the S5 helix.
Results
We generated trafficking scores for 220 of 231 missense variants in the pilot region. For 5 of 5 variants, high-throughput trafficking scores validated when tested in single variant flow cytometry and confocal microscopy experiments. We further explored these results with planar patch electrophysiology and found that loss-of-trafficking variants do not produce I. Conversely, but expectedly, some variants that traffic normally were still functionally compromised.
Conclusion
We describe a new method for detecting K11.1 trafficking-deficient variants in a multiplexed assay. This new method accurately generated trafficking data for variants in K11.1 and is extendable both to all residues in K11.1 and to other cell surface proteins.

Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Heart Rhythm: 29 Nov 2020; 17:2180-2189
Kozek KA, Glazer AM, Ng CA, Blackwell D, ... Roden DM, Kroncke BM
Heart Rhythm: 29 Nov 2020; 17:2180-2189 | PMID: 32522694
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Abstract

Bipolar radiofrequency ablation for ventricular tachycardias originating from the interventricular septum: Safety and efficacy in a pilot cohort study.

Della Bella P, Peretto G, Paglino G, Bisceglia C, ... Mazzone P, Frontera A
Background
Interest has grown in recent years in bipolar radiofrequency ablation (B-RFA). However, indications and outcome in patients with ventricular tachycardia (VT) are still to be defined.
Objective
The purpose of this study was to describe patient selection, safety and effectiveness of B-RFA, in a pilot cohort study of patients with nonischemic dilated cardiomyopathy (NIDCM) and drug-refractory VT.
Methods
We enrolled 21 patients with NIDCM (mean age 66±10 years; 18/21 (86%) men; left ventricular ejection fraction 35%±14%; 100% redo procedures) scheduled for a B-RFA procedure because of drug-refractory VT of suspected septal (interventricular septum [IVS]) origin. After electroanatomic mapping by using the CARTO®3 system, B-RFA was performed in all patients. Short- and long-term outcomes, including procedural success, major complications, and occurrence of major ventricular arrhythmias (MVAs), were evaluated at 25±8 months of follow-up (FU).
Results
Endocardial mapping showed IVS scar in all patients and extra-IVS in 7 patients (33%). B-RFA was performed at an average power of 33 W, for 60-90 seconds, over a 4.1 cm area, with 13±3 mm distance between catheters tips. The impedance drop was 27±4 Ω. The primary end point of noninducibility of the target clinical VT was obtained in 20 patients (95%). During FU, MVAs were documented in 7 patients (33%). FU MVAs occurred in all (100%) patients with extra-IVS localizations (7 of 7) or inflammatory nonischemic cardiomyopathy etiology (2 of 2). IVS thinning (tip-to-tip catheter distance < 5 mm) represented the only anatomical limitation to B-RFA.
Conclusion
B-RFA is feasible in patients with NIDCM and drug-refractory VT of septal origin. Extra-IVS substrate and inflammatory NIDCM etiology were associated with an adverse outcome.

Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Heart Rhythm: 29 Nov 2020; 17:2111-2118
Della Bella P, Peretto G, Paglino G, Bisceglia C, ... Mazzone P, Frontera A
Heart Rhythm: 29 Nov 2020; 17:2111-2118 | PMID: 32599177
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Impact:
Abstract

Common and rare susceptibility genetic variants predisposing to Brugada syndrome in Thailand.

Makarawate P, Glinge C, Khongphatthanayothin A, Walsh R, ... Veerakul G, Nademanee K
Background
Mutations in SCN5A are rarely found in Thai patients with Brugada syndrome (BrS). Recent evidence suggested that common genetic variations may underlie BrS in a complex inheritance model.
Objective
The purpose of this study was to find common and rare/low-frequency genetic variants predisposing to BrS in persons in Thailand.
Methods
We conducted a genome-wide association study (GWAS) to explore the association of common variants in 154 Thai BrS cases and 432 controls. We sequenced SCN5A in 131 cases and 205 controls. Variants were classified according to current guidelines, and case-control association testing was performed for rare and low-frequency variants.
Results
Two loci were significantly associated with BrS. The first was near SCN5A/SCN10A (lead marker rs10428132; odds ratio [OR] 2.4; P = 3 × 10). Conditional analysis identified a novel independent signal in the same locus (rs6767797; OR 2.3; P = 2.7 × 10). The second locus was near HEY2 (lead marker rs3734634; OR 2.5; P = 7 × 10). Rare (minor allele frequency [MAF] <0.0001) coding variants in SCN5A were found in 8 of the 131 cases (6.1% in cases vs 2.0% in controls; P = .046; OR 3.3; 95% confident interval [CI] 1.0-11.1), but an enrichment of low-frequency (MAF<0.001 and >0.0001) variants also was observed in cases, with 1 variant (SCN5A: p.Arg965Cys) detected in 4.6% of Thai BrS patients vs 0.5% in controls (P = 0.015; OR 9.8; 95% CI 1.2-82.3).
Conclusion
The genetic basis of BrS in Thailand includes a wide spectrum of variant frequencies and effect sizes. As previously shown in European and Japanese populations, common variants near SCN5A and HEY2 are associated with BrS in the Thai population, confirming the transethnic transferability of these 2 major BrS loci.

Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Heart Rhythm: 29 Nov 2020; 17:2145-2153
Makarawate P, Glinge C, Khongphatthanayothin A, Walsh R, ... Veerakul G, Nademanee K
Heart Rhythm: 29 Nov 2020; 17:2145-2153 | PMID: 32619740
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Abstract

Transvenous phrenic nerve stimulation for central sleep apnea is safe and effective in patients with concomitant cardiac devices.

Nayak HM, Patel R, McKane S, James KJ, ... Costanzo MR, Augostini R
Background
Central sleep apnea is common in heart failure patients. Transvenous phrenic nerve stimulation (TPNS) requires placing a lead to stimulate the phrenic nerve and activate the diaphragm. Data are lacking concerning the safety and efficacy of TPNS in patients with concomitant cardiovascular implantable electronic devices (CIEDs).
Objective
To report the safety and efficacy of TPNS in patients with concomitant CIEDs.
Methods
In the remedē System Pivotal Trial, 151 patients underwent TPNS device implant. This analysis compared patients with concomitant CIEDs to those without with respect to safety, implant metrics, and efficacy of TPNS. Safety was assessed using incidence of adverse events and device-device interactions. A detailed interaction protocol was followed. Implant metrics included overall TPNS implantation success. Efficacy endpoints included changes in the apnea-hypopnea index (AHI) and quality of life.
Results
Of 151 patients, 64 (42%) had a concomitant CIED. There were no significant differences between the groups with respect to safety. There were 4 CIED oversensing events in 3 patients leading to 1 inappropriate defibrillator shock and delivery of antitachycardia pacing. There was no difference in efficacy between the CIED and non-CIED subgroups receiving TPNS, with both having similar percentages of patients who achieved ≥50% reduction in AHI and quality-of-life improvement.
Conclusion
Concomitant CIED and TPNS therapy is safe. The presence of a concomitant CIED did not seem to impact implant metrics, implantation success, and TPNS efficacy. A detailed interaction protocol should be followed to minimize the incidence of device-device interaction.

Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Heart Rhythm: 29 Nov 2020; 17:2029-2036
Nayak HM, Patel R, McKane S, James KJ, ... Costanzo MR, Augostini R
Heart Rhythm: 29 Nov 2020; 17:2029-2036 | PMID: 32619739
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Impact:
Abstract

Determining the optimal duration for premature ventricular contraction monitoring.

Hsia BC, Greige N, Patel SK, Clark RM, ... Di Biase L, Krumerman A
Background
Premature ventricular contractions (VPC) have hour-to-hour and day-to-day variation. High VPC burden correlates with cardiomyopathy.
Objective
To determine the optimal duration for ambulatory electrocardiogram monitoring for accurate assessment of VPC burden.
Methods
Our group performed a retrospective analysis on patch monitors used for any indication with overall VPC burden ≥5.0% between February 1, 2016, and February 1, 2020. We generated cumulative daily VPC averages for each day of wear and performed linear regression analysis between each cumulative daily average and overall burden. Patients were divided into groups based on low or high VPC frequency, and the analysis was repeated. Split-sample validation was used to internally validate the overall prediction model.
Results
A total of 116 patches representing 107 patients (mean age: 64.5; female: 48%) were analyzed. Mean overall VPC burden was 13.4% ± 7.5% (range: 5.0%-42.0%). Day 1 R was 60%, P < .001, and continued to increase to R 88%, P < .001 at day 14. Median percent and absolute error decreased from 22.70% (interquartile range [IQR]: 9.73-34.39) and 2.58% (IQR: 1.24-4.59) at day 1 to 5.62% (IQR: 2.82-8.39) and 0.55% (IQR: 0.28-1.05) at day 14. Patients with higher overall VPC frequencies achieved a more rapid rise in R relative to those with lower frequencies. Split-sample validation supported the internal validity of our linear regression prediction model.
Conclusion
Mobile telemetry for a period of ∼7 days accurately reflects overall VPC burden. Measurement of VPC burden for only 24-48 hours may not accurately reflect total burden. Monitoring for 2 weeks or longer adds little additional VPC information.

Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Heart Rhythm: 29 Nov 2020; 17:2119-2125
Hsia BC, Greige N, Patel SK, Clark RM, ... Di Biase L, Krumerman A
Heart Rhythm: 29 Nov 2020; 17:2119-2125 | PMID: 32679267
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Impact:
Abstract

Amplitude of QRS complex within initial 40 ms in V (VQRS): Novel electrocardiographic criterion for predicting accurate localization of outflow tract ventricular arrhythmia origin.

Xia Y, Liu Z, Liu J, Li X, ... Yu M, Fang P
Background
The initial depolarization vector of outflow tract (OT) ventricular arrhythmia (VA) varies in different origins, which may help to predict OT-VA origin more accurately.
Objective
The purpose of this study was to develop a more accurate electrocardiographic (ECG) criterion for differentiating between left and right OT-VA origins.
Methods
We studied 275 patients with successful ablation in the right ventricular outflow tract (RVOT) (n = 207) or left ventricular outflow tract (LVOT) (n = 68) in the development cohort. Amplitude of the QRS complex within initial 40 ms (QRS) in precordial leads was measured. A novel criterion for identifying OT-VA origin was developed based on the development cohort. Predictive performance of novel criterion was further validated by comparing with previous ECG criteria (VS/VR index, V transition ratio, and transition zone index) in the validation cohort with 107 patients (RVOT 75; LVOT 32).
Results
QRS of identical precordial leads were significantly greater in the LVOT group than the RVOT group (P <.05). In the development cohort, QRS of V (VQRS) exhibited the greatest area under the curve of 0.950, with cutoff ≥0.52 mV predicting LVOT origin (sensitivity 86.0%; specificity 94.6%). In the validation cohort, VQRS ≥0.52 mV outperformed previous criteria in predictive performance (accuracy 90.7%; sensitivity 84.4%; specificity 93.3%). This advantage of VQRS over previous criteria also held true for subgroups of transition zone index = 0 and V R/S transition.
Conclusion
VQRS is a novel and accurate ECG criterion to predict OT-VA origin that outperforms previous criteria.

Copyright © 2020. Published by Elsevier Inc.

Heart Rhythm: 29 Nov 2020; 17:2164-2171
Xia Y, Liu Z, Liu J, Li X, ... Yu M, Fang P
Heart Rhythm: 29 Nov 2020; 17:2164-2171 | PMID: 32653429
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Impact:
Abstract

Toward detection of conduction tissue during cardiac surgery: Light at the end of the tunnel?

Sachse FB, Johnson J, Cottle B, Mondal A, Hitchcock R, Kaza AK

Postoperative conduction block requiring lifetime pacemaker placement continues to be a considerable source of morbidity for patients undergoing repair of congenital heart defects. Damage to the cardiac conduction system (CCS) during surgical procedures is thought to be a major cause of conduction block. Intraoperative identification and avoidance of the CCS is thus a key strategy to improve surgical outcomes. A number of approaches have been developed to avoid conduction tissue damage and mitigate morbidity. Here we review the historical and contemporary approaches for identification of conduction tissue during cardiac surgery. The established approach for intraoperative identification is based on anatomic landmarks established in extensive histologic studies of normal and diseased heart. We focus on landmarks to identify the sinus and atrioventricular nodes during cardiac surgery. We also review technologies explored for intraoperative tissue identification, including electrical impedance measurements and electrocardiography. We describe new optical approaches, in particular, and optical spectroscopy and fiberoptic confocal microscopy (FCM) for identification of CCS regions and working myocardium during surgery. As a template for translation of future technology developments, we describe research and regulatory pathways to translate FCM for cardiac surgery. We suggest that along with more robust approaches to surgeon training, including awareness of fundamental anatomic studies, optical approaches such as FCM show promise in aiding surgeons with repairs of heart defects. In particular, for complex defects, these approaches can complement landmark-based identification of conduction tissue and thus help to avoid injury to the CCS due to surgical procedures.

Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Heart Rhythm: 29 Nov 2020; 17:2200-2207
Sachse FB, Johnson J, Cottle B, Mondal A, Hitchcock R, Kaza AK
Heart Rhythm: 29 Nov 2020; 17:2200-2207 | PMID: 32659372
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Impact:
Abstract

Alcohol consumption and risk of atrial fibrillation in asymptomatic healthy adults.

Cha MJ, Oh GC, Lee H, Park HE, Choi SY, Oh S
Background
Excessive alcohol consumption is related to atrial fibrillation (AF) development in the general population.
Objective
The purpose of this study was to investigate the effect of alcohol consumption on new-onset AF development in asymptomatic healthy individuals.
Methods
Asymptomatic healthy adults (age <75 years; body mass index <30 kg/m) undergoing routine health examinations from 2007 to 2015 were screened. Those with sinus rhythm and without any previously diagnosed medical or surgical illness were recruited for analysis. The primary outcome was new-onset AF. Secondary outcomes were a composite of non-AF cardiac events, including clinically significant tachy- or bradyarrhythmias, acute myocardial infarction, heart failure, or cardiac death.
Results
Among 19,634 individuals (50% male; age 19-74 years), 199 cardiac events were recorded, including new-onset AF (n = 160), acute myocardial infarction (n = 30), and clinically significant tachy- or bradyarrhythmia (n =19), during mean follow-up of 7.0 ± 2.8 years. The incidence of new-onset AF was higher in drinkers (hazard ratio [HR] 2.21; 95% confidence interval [CI] 1.55-3.14; P <.001), whereas composite non-AF cardiac events were not correlated to alcohol. There was a dose-dependent increase in the risk of AF according to the amount of alcohol consumed, and the risk increased more abruptly in men than in women. The risk of AF was highest in frequent binge drinkers (HR 3.15; 95% CI 1.98-4.99; P <.001), compared to infrequent light drinkers.
Conclusion
In the asymptomatic healthy population, drinking increases the risk of new-onset AF in a dose-dependent manner, regardless of sex. Frequent binge drinking should be avoided.

Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Heart Rhythm: 29 Nov 2020; 17:2086-2092
Cha MJ, Oh GC, Lee H, Park HE, Choi SY, Oh S
Heart Rhythm: 29 Nov 2020; 17:2086-2092 | PMID: 32673797
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Impact:
Abstract

Catheter-free ablation of infarct scar through proton beam therapy: Tissue effects in a porcine model.

Hohmann S, Deisher AJ, Konishi H, Rettmann ME, ... Herman MG, Packer DL
Background
Scar-related ventricular arrhythmias are common after myocardial infarction. Catheter ablation can improve prognosis, but the procedure is invasive and results are not always satisfactory. Noninvasive, catheter-free ablation using ionizing radiation has recently gained interest among electrophysiologists, but the tissue effects and physiological outcome have not been fully characterized.
Objective
The purpose of this study was to investigate the structural effects of cardiac scanned pencil beam proton therapy on infarct scar, the time course of imaging biomarkers, arrhythmias, and cardiac function in a porcine model.
Methods
Fourteen infarcted swine underwent proton beam treatment of the scar (40 or 30 Gy) and were followed for up to 30 weeks. Magnetic resonance imaging was performed every 4 weeks.
Results
Treated scar areas showed a significantly lower fraction of surviving myocytes at 30 weeks compared to untreated scar (30.1% ± 18.5% and 59.9% ± 10.1% in treated and untreated infarct, respectively), indicating scar homogenization. Four animals died suddenly during follow-up, all from documented monomorphic ventricular tachycardia. Cardiac function remained stable over the course of the study. Distinct imaging morphologies corresponded to certain tissue dose ranges and time points.
Conclusion
Radioablation of cardiac infarct scar leads to significant homogenization of the scar, replicating the histologic effects of radiofrequency ablation. These changes correspond to distinct imaging morphologies on delayed contrast-enhanced cardiac magnetic resonance imaging, enabling noninvasive confirmation of tissue ablation effects The present study is the first to thoroughly investigate the structural effects of cardiac proton beam therapy in infarcted myocardium.

Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Heart Rhythm: 29 Nov 2020; 17:2190-2199
Hohmann S, Deisher AJ, Konishi H, Rettmann ME, ... Herman MG, Packer DL
Heart Rhythm: 29 Nov 2020; 17:2190-2199 | PMID: 32673796
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Impact:
Abstract

New algorithm for accessory pathway localization focused on screening septal pathways in pediatric patients with Wolff-Parkinson-White syndrome.

Baek SM, Song MK, Uhm JS, Kim GB, Bae EJ
Background
Published algorithms for accessory pathway localization in Wolff-Parkinson-White (WPW) syndrome are inaccurate in pediatric patients, especially for septal pathways.
Objective
We aimed to develop a new algorithm that is sensitive for septal pathways and more applicable in pediatric patients.
Methods
In 120 patients (mean age: 11.7 ± 3.9 years) who underwent catheter ablation for WPW syndrome, the candidate criteria for new algorithm were searched by comparing electrocardiography parameters and accessory pathway locations. A new algorithm was designed to increase the sensitivity for septal pathways. For validation, 142 patients (mean age: 15.8 ± 3.7 years) were additionally evaluated. New and published algorithms were applied to electrocardiography of 262 patients and the results were compared.
Results
The new algorithm achieved its best discrimination by combining several parameters together in each step: (1) QRS polarity in V and QRS shape in lead I for left/right discrimination, and (2) delta wave polarity in V, QRS transition in precordial leads, and delta wave polarity in lead III for septal pathway screening. The new algorithm showed higher sensitivity for septal pathways (95.7%) than 7 published algorithms (average: 62.1%), with satisfactory positive predictive value (77.9%). Delta wave polarity in V among septal pathways and QRS axis among right anteroseptal pathway showed age-related trend; this could be the reason for the lower accuracy in localizing septal pathways in children.
Conclusion
The inaccuracy of published algorithms in pediatric patients is due to the age-related trend in the electrocardiography of septal pathways. The new algorithm was superior for localizing septal pathways in pediatric patients.

Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Heart Rhythm: 29 Nov 2020; 17:2172-2179
Baek SM, Song MK, Uhm JS, Kim GB, Bae EJ
Heart Rhythm: 29 Nov 2020; 17:2172-2179 | PMID: 32681992
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Impact:
Abstract

Is transesophageal echocardiography necessary in patients undergoing ablation of atrial fibrillation on an uninterrupted direct oral anticoagulant regimen? Results from a prospective multicenter registry.

Patel K, Natale A, Yang R, Trivedi C, ... Lakkireddy D, Di Biase L
Background
Thromboembolic stroke is a rare but devastating consequence of atrial fibrillation (AF) ablation. Transesophageal echocardiography (TEE) is recommended to rule out left atrial appendage thrombus; however, its use is variable.
Objective
The purpose of this study was to assess whether TEE is mandatory in patients undergoing AF ablation on uninterrupted direct oral anticoagulants (DOACs).
Methods
Data from our prospective multicenter registry of patients with AF undergoing radiofrequency catheter ablation on uninterrupted DOACs were analyzed. All the included patients were on anticoagulation for at least 4 weeks before ablation. All AF ablation procedures were performed under intracardiac echocardiography guidance. Before transseptal puncture, heparin bolus was administered, followed by continuous infusion, with a target activated clotting time of >300 seconds.
Results
A total of 6186 patients (3180 on apixaban [51.4%], 2528 on rivaroxaban [40.9%], 404 on dabigatran [6.5%], and 74 on edoxaban [1.2%]) were analyzed. The mean age of the study population was 69.4 ± 10.3 years; 4194 patients (67.8%) were male, and 5120 patients (82.8%) had persistent and long-standing persistent AF. The mean CHADS-VASc score was 2.86 ± 1.58; the mean CHADS score was 1.65 ± 1.14. Intracardiac echocardiography ruled out left atrial appendage and left atrial thrombi in all patients and revealed \"smoke\" in 1672 patients (27.03%). Transient ischemic attack was noted in 1 patient with long-standing persistent AF in the setting of a missed dose of rivaroxaban before ablation.
Conclusion
Our study showed that performing AF ablation in patients on uninterrupted DOACs without TEE is safe and feasible in high stroke risk patients. Elimination of routine preablation TEE would have significant economic and clinical implications.

Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Heart Rhythm: 29 Nov 2020; 17:2093-2099
Patel K, Natale A, Yang R, Trivedi C, ... Lakkireddy D, Di Biase L
Heart Rhythm: 29 Nov 2020; 17:2093-2099 | PMID: 32681991
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Impact:
Abstract

Off-label dosing of non-vitamin K antagonist oral anticoagulants and clinical outcomes in Asian patients with atrial fibrillation.

Chan YH, Chao TF, Chen SW, Lee HF, ... Lip GYH, Chen SA
Background
Off-label dosing non-vitamin K antagonist oral anticoagulants (NOACs) are commonly prescribed for Asian patients with atrial fibrillation (AF).
Objective
The purpose of this study was to investigate the associations between inappropriate dosing of NOACs and clinical outcomes.
Methods
We used medical data from a multicenter health care system in Taiwan, which included 2068, 5135, 2589, 1483, and 2342 AF patients taking dabigatran, rivaroxaban, apixaban, edoxaban, and warfarin, respectively. The risks of ischemic stroke/systemic embolism (IS/SE) and major bleeding in patients treated with underdosing or overdosing NOACs were compared to those of on-label dosing NOACs and warfarin.
Results
About 27% and 5% of AF patients were treated with underdosing and overdosing NOACs, respectively. Compared to on-label dosing, underdosing NOACs were associated with a significantly higher risk of IS/SE (adjusted hazard ratio [aHR] 1.59; 95% confidence interval [CI] 1.25-2.02; P <.001), whereas overdosing NOACs were associated with a significantly higher risk of major bleeding (aHR 2.01; 95% CI 1.13-3.56; P = .017). Compared to warfarin, the 4 on-label dosing NOACs were associated with a comparable risk of IS/SE and a significantly lower risk of major bleeding, whereas underdosing NOACs were associated with a higher risk of IS/SE (aHR 1.46; P = .012).
Conclusion
About 3 in 10 Asian AF patients were treated with off-label dosing NOACs in daily practice. Compared to on-label dosing, underdosing was associated with a higher risk of IS/SE, whereas overdosing was associated with a higher risk of major bleeding. Thus, even for Asian AF patients at higher risk for bleeding, NOACs still should be prescribed at the dosing based on clinical trial criteria and guideline recommendations.

Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Heart Rhythm: 29 Nov 2020; 17:2102-2110
Chan YH, Chao TF, Chen SW, Lee HF, ... Lip GYH, Chen SA
Heart Rhythm: 29 Nov 2020; 17:2102-2110 | PMID: 32702416
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Impact:
Abstract

Predictors of atrial mechanical sensing and atrioventricular synchrony with a leadless ventricular pacemaker: Results from the MARVEL 2 Study.

Garweg C, Khelae SK, Steinwender C, Chan JYS, ... Wood N, Chinitz L
Background
The MARVEL (Micra Atrial TRacking Using a Ventricular AccELerometer) 2 study assessed the efficacy of atrioventricular (AV) synchronous pacing with a Micra leadless pacemaker. Average atrioventricular synchrony (AVS) was 89.2%. Previously, low amplitude of the Micra-sensed atrial signal (A4) was observed to be a factor of low AVS.
Objective
The purpose of this study was to identify predictors of A4 amplitude and high AVS.
Methods
We analyzed 64 patients enrolled in MARVEL 2 who had visible P waves on electrocardiogram for assessing A4 amplitude and 40 patients with third-degree AV block for assessing AVS at rest. High AVS was defined as >90% correct atrial-triggered ventricular pacing. The association between clinical factors and echocardiographic parameters with A4 amplitude was investigated using a multivariable model with lasso variable selection. Variables associated with A4 amplitude together with premature ventricular contraction burden, sinus rate, and sinus rate variability (standard deviation of successive differences of P-P intervals [SDSD]) were assessed for association with AVS.
Results
In univariate analysis, low A4 amplitude was inversely related to atrial function assessed by E/A ratio and e\'/a\' ratio, and was directly related to atrial contraction excursion (ACE) and atrial strain (Ɛa) on echocardiography (all P ≤.05). The multivariable lasso regression model found coronary artery bypass graft history, E/A ratio, ACE, and Ɛa were associated with low A4 amplitude. E/A ratio and SDSD were multivariable predictors of high AVS, with >90% probability if E/A <0.94 and SDSD <5 bpm.
Conclusion
Clinical parameters and echocardiographic markers of atrial function are associated with A4 signal amplitude. High AVS can be predicted by E/A ratio <0.94 and low sinus rate variability at rest.

Copyright © 2020 The Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Heart Rhythm: 29 Nov 2020; 17:2037-2045
Garweg C, Khelae SK, Steinwender C, Chan JYS, ... Wood N, Chinitz L
Heart Rhythm: 29 Nov 2020; 17:2037-2045 | PMID: 32717315
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Impact:
Abstract

Effect of QRS area reduction and myocardial scar on the hemodynamic response to cardiac resynchronization therapy.

Okafor O, Umar F, Zegard A, van Dam P, ... Marshall H, Leyva F
Background
Vectorcardiographic QRS area (QRS) predicts clinical outcomes after cardiac resynchronization therapy (CRT). Myocardial scar adversely affects clinical outcomes after CRT.
Objective
The purpose of this study in patients with an ideally deployed quadripolar left ventricular (LV) lead (QUAD) was to determine whether reducing QRS leads to an acute hemodynamic response (AHR) and whether scar affects this interaction.
Methods
Patients (n = 26; age 69.2 ± 9.12 years [mean ± SD]) underwent assessment of the maximum rate of change of LV pressure (ΔLV dP/dt) during CRT using various left ventricular pacing locations (LVPLs). Cardiac magnetic resonance (CMR) scan was used to localize LV myocardial scar.
Results
Interindividually, ΔQRS (area under the receiver operating characteristic curve [AUC] 0.81; P <.001) and change in QRS duration (ΔQRSd) (AUC 0.76; P <.001) predicted ΔLV dP/dt after CRT. Scar burden correlated with ΔQRS (r = 0.35; P = .003), ΔQRS (r = 0.35; P = .003), and ΔQRSd (r = 0.46; P <.001). A reduction in QRS was observed with LVPLs remote from scar (-3.28 ± 38.1 μVs) or in LVPLs in patients with no scar at all (-43.8 ± 36.8 μVs), whereas LVPLs over scar increased QRS (22.2 ± 58.4 μVs) (P <.001 for all comparisons). LVPLs within 1 scarred LV segment were associated with lower ΔLV dP/dt (-2.21% ± 11.5%) than LVPLs remote from scar (5.23% ± 10.3%; P <.001) or LVPLs in patients with no scar at all (10.2% ± 7.75%) (both P <.001).
Conclusion
Reducing QRS improves the AHR to CRT. Myocardial scar adversely affects ΔQRS and the AHR. These findings may support the use of ΔQRS and CMR in optimizing CRT using QUAD.

Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Heart Rhythm: 29 Nov 2020; 17:2046-2055
Okafor O, Umar F, Zegard A, van Dam P, ... Marshall H, Leyva F
Heart Rhythm: 29 Nov 2020; 17:2046-2055 | PMID: 32717314
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Impact:
Abstract

High-rate pacing guided by short-term variability of repolarization prevents imminent ventricular arrhythmias automatically by an implantable cardioverter-defibrillator in the chronic atrioventricular block dog model.

Smoczyńska A, Loen V, Aranda A, Beekman HDM, Meine M, Vos MA
Background
The anesthetized, complete chronic atrioventricular block (CAVB) dog model allows reproducible inducibility of torsades de pointes (TdP) arrhythmias due to ventricular remodeling and after a challenge with an I blocker. High-rate pacing (HRP) prevents ventricular arrhythmias but has long-term detrimental effects on cardiac function when applied continuously. Temporal dispersion of repolarization, quantified as short-term variability (STV), increases before ventricular arrhythmias and has been proposed as a marker to guide HRP.
Objective
The purpose of this proof-of-principle study was to show that automatically determined STV can guide HRP to prevent imminent ventricular arrhythmias.
Methods
Eight CAVB dogs were implanted with an implantable cardioverter-defibrillator (ICD) with software to automatically determine STV (STV) in real time. During HRP, STV was measured offline from right ventricular (RV) electrograms (EGMs) and left ventricular (LV) monophasic action potential durations (MAPDs) (STV). The CAVB dogs were challenged twice with dofetilide (0.025 mg/kg intravenously over 5 minutes or until the first TdP). In experiment 1, the individual STV threshold before the first arrhythmic event was determined and programmed into the ICD. In experiment 2, HRP with 100 bpm was initiated automatically once the STV threshold was reached.
Results
In experiment 1, 8 of 8 dogs had repetitive TdP, and STV increased from 0.96 ± 0.42 ms to 2.10 ± 1.26 ms (P <.05). In experiment 2, all dogs reached the STV threshold. HRP decreased STV from 2.02 ± 1.12 ms to 0.78 ± 0.28 ms, which was accompanied by prevention of TdP in 7 of 8 dogs.
Conclusion
STV can guide HRP automatically by an ICD to prevent ventricular arrhythmias.

Copyright © 2020 The Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Heart Rhythm: 29 Nov 2020; 17:2078-2085
Smoczyńska A, Loen V, Aranda A, Beekman HDM, Meine M, Vos MA
Heart Rhythm: 29 Nov 2020; 17:2078-2085 | PMID: 32710972
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Impact:
Abstract

Mind the gap: Knowledge deficits in evaluating young sudden cardiac death.

Paratz E, Semsarian C, La Gerche A

Sudden cardiac arrest affects around half a million people aged under 50 years old annually, with a 90% mortality rate. Despite high patient numbers and clear clinical need to improve outcomes, many gaps exist in the evidence underpinning patients\' management. Domains identifying the greatest barriers to conducting trials are the prehospital and forensic settings, which also provide care to the majority of patients. Addressing gaps in evidence along each point of the cardiac arrest trajectory is a key clinical priority.

Crown Copyright © 2020. Published by Elsevier Inc. All rights reserved.

Heart Rhythm: 29 Nov 2020; 17:2208-2214
Paratz E, Semsarian C, La Gerche A
Heart Rhythm: 29 Nov 2020; 17:2208-2214 | PMID: 32721478
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Impact:
Abstract

Progressive implantable cardioverter-defibrillator therapies for ventricular tachycardia: The efficacy and safety of multiple bursts, ramps, and low-energy shocks.

Strik M, Ramirez FD, Welte N, Bonnin T, ... Ploux S, Bordachar P
Background
The Heart Rhythm Society, the European Heart Rhythm Association, the Asia Pacific Heart Rhythm Society, the Latin American Heart Rhythm Society expert consensus statement on optimal implantable cardioverter-defibrillator programming recommends burst antitachycardia pacing (ATP) for the treatment of ventricular tachycardia (VT) up to high rates. The number of bursts is not specified, and treatment by ramps or low-energy shocks is not recommended.
Objectives
We investigated the efficacy and safety of progressive therapies for VTs between 150 and 200 beats/min. After 3 failed bursts, we compared 3 ramps vs 3 bursts followed by a low-energy shock vs high-energy shock.
Methods
Using remote monitoring, we included monomorphic VT episodes treated with ≥1 burst.
Results
A total of 1126 VT episodes were included. A single burst was as likely to terminate VT between 150 and 200 beats/min as VT between 200 and 230 beats/min (63% vs 64%; P=.41), but was more likely to accelerate the latter (3.2% vs 0.25%; P<.01). For VT <200 beats/min, the likelihood of ATP success increased progressively (73% with 2 bursts, 78% with 3 bursts). Three additional bursts further increased VT termination to 89%, similar to the success rate with 3 additional ramps (88%; P=.17). Programming 6 bursts is associated with the probability of acceleration requiring shock of 6.6%. A low-energy first shock was less successful than a high-energy shock (66% vs 86%; P<.01) and more likely to accelerate VT (17% vs 0%; P<.01).
Conclusion
Programming up to 6 burst ATP therapies for VTs 150-200 beats/min can avoid implantable cardioverter-defibrillator shocks in most patients. Ramp ATP after failed bursts were similarly effective. Low-energy shocks are less effective and more arrhythmogenic than high-energy shocks.

Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Heart Rhythm: 29 Nov 2020; 17:2072-2077
Strik M, Ramirez FD, Welte N, Bonnin T, ... Ploux S, Bordachar P
Heart Rhythm: 29 Nov 2020; 17:2072-2077 | PMID: 32739474
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Impact:
Abstract

Morbidity and mortality in patients precluded for transvenous pacemaker implantation: Experience with a leadless pacemaker.

Garg A, Koneru JN, Fagan DH, Stromberg K, ... Cheng A, Ellenbogen KA
Background
The Micra transcatheter pacemaker is a safe and effective alternative to transvenous permanent pacemakers (TV-PPMs). However, the safety profile and mortality outcomes of Micra implantation in patients deemed poor candidates for TV-PPM are incompletely understood.
Objective
The purpose of this study was to evaluate safety and all-cause mortality in patients undergoing Micra implantation stratified by whether they were precluded for therapy with a TV-PPM.
Methods
Patients from the Micra clinical trials were divided into groups on the basis of whether the implanter considered the patient to be precluded from receiving a TV-PPM. Micra groups were compared with one another as well as with a historical cohort of patients who received a single-chamber TV-PPM.
Results
A total of 2817 patients underwent a Micra implantation attempt, of whom 546 (19%) patients deemed ineligible for TV-PPM implantation for reasons such as venous access issues or prior device infections. Both acute mortality (2.75% vs 1.32%; P=.022) and total mortality at 36 months (38.1% vs 20.6%; P<.001) were significantly higher in the precluded group than in the nonprecluded group. Mortality was similar among nonprecluded patients and patients implanted with a TV-PPM. The major complication rate through 36 months was similar between the 2 Micra groups (3.81% vs 4.30%; P=.40).
Conclusion
All-cause mortality is higher in Micra patients deemed ineligible for TV-PPM implantation than in nonprecluded Micra patients and those who received a TV-PPM, in part related to a higher incidence of chronic comorbidities in these patients. The overall major complication rate was low and did not differ by preclusion status.
Clinical trial registration
Micra Post-Approval Registry ClinicalTrials.gov identifier: NCT02536118; Micra Continued Access Study ClinicalTrials.gov identifier: NCT02488681; Micra Transcatheter Pacing Study ClinicalTrials.gov identifier: NCT02004873; Medtronic Product Surveillance Registry ClinicalTrials.gov identifier: NCT01524276.

Copyright © 2020 Heart Rhythm Society. All rights reserved.

Heart Rhythm: 29 Nov 2020; 17:2056-2063
Garg A, Koneru JN, Fagan DH, Stromberg K, ... Cheng A, Ellenbogen KA
Heart Rhythm: 29 Nov 2020; 17:2056-2063 | PMID: 32763431
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Impact:
Abstract

Safety of magnetic resonance imaging scanning in patients with cardiac resynchronization therapy-defibrillators incorporating quadripolar left ventricular leads.

Rinaldi CA, Vitoff PJ, Nair DG, Bernstein R, ... Tse HF, Green UB
Background
Magnetic resonance imaging (MRI) scanning of magnetic resonance (MR)-conditional cardiac implantable cardioverter-defibrillators (ICDs) can be performed safely following specific protocols. MRI safety with cardiac resynchronization therapy-defibrillators (CRT-Ds) incorporating quadripolar left ventricular (LV) leads is less clear.
Objective
The purpose of this study was to evaluate the safety and effectiveness of ICDs and CRT-D systems with quadripolar LV leads after an MRI scan.
Methods
The ENABLE MRI Study included 230 subjects implanted with a Boston Scientific ImageReady ICD (n = 39) or CRT-D (n = 191) incorporating quadripolar LV leads undergoing nondiagnostic 1.5-T MRI scans (lumbar and thoracic spine imaging) a minimum of 6 weeks postimplant. Pacing capture thresholds (PCTs), sensing amplitudes (SAs), and impedances were measured before and 1 month post-MRI using the same programmed LV pacing vectors. The ability to sense/treat ventricular fibrillation (VF) was assessed in a subset of patients.
Results
A total of 159 patients completed a protocol-required MRI scan (MRI Protection Mode turned on) with no scan-related complications. All right ventricular (RV) and left LV PCT and SA effectiveness endpoints were met: RV PCT 99% (145/146 patients), LV PCT 100% (120/120), RV SA 99% (145/146), and LV SA 98% (116/118). In no instances did MRI result in a change in pacing vector or lead revision. All episodes of VF were appropriately sensed and treated.
Conclusion
This first evaluation of predominantly CRT-D systems with quadripolar LV leads undergoing 1.5-T MRI confirmed that scanning was safe with no significant changes in RV/LV PCT, SA, programmed vectors, and VF treatment, thus suggesting that MRI in patients having a device with quadripolar leads can be performed without negative impact on CRT delivery.

Copyright © 2020 The Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Heart Rhythm: 29 Nov 2020; 17:2064-2071
Rinaldi CA, Vitoff PJ, Nair DG, Bernstein R, ... Tse HF, Green UB
Heart Rhythm: 29 Nov 2020; 17:2064-2071 | PMID: 32911050
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Impact:
Abstract

Mortality after cardioverter-defibrillator replacement: Results of the DECODE survival score index.

Berisso MZ, Martignani C, Ammendola E, Narducci ML, ... Malacrida M, Biffi M
Background
Device replacement is the ideal time to reassess health care goals regarding continuing implantable cardioverter-defibrillator (ICD) therapy. Only few data are available on the decision making at this time.
Objectives
The goals of this study were to identify factors associated with poor prognosis at the time of ICD replacement and to develop a prognostic index able to stratify those patients at risk of dying early.
Methods
Detect long-term complications after ICD replacement (DECODE) was a prospective, single-arm, multicenter cohort study aimed at estimating long-term complications in a large population of patients who underwent ICD/cardiac resynchronization therapy - defibrillator replacement. Potential predictors of death were investigated, and all these factors were gathered into a survival score index (SUSCI).
Results
We included 983 consecutive patients (median age 71 years; 76% men; 55% with ischemic cardiomyopathy; 47% with cardiac resynchronization therapy - defibrillator). During a median follow-up period of 761 days (interquartile range 628-904 days), 114 patients (12%) died. In multivariate Cox regression analysis, New York Heart Association class III/IV, ischemic cardiomyopathy, body mass index < 26 kg/m, insulin administration, age ≥ 75 years, history of atrial fibrillation, and hospitalization within 30 days before ICD replacement remained associated with death. The survival score index showed a good discriminatory power with a hazard ratio of 2.6 (95% confidence interval 2.2-3.1; P < .0001). The risk of death increased according to the severity of the risk profile ranging from 0% (low risk) to 47% (high risk).
Conclusion
A simple score that includes a limited set of variables appears to be predictive of total mortality in an unselected real-world population undergoing ICD replacement. Evaluation of the patient\'s profile may assist in predicting vulnerability and should prompt individualized options, especially for high-risk patients.

Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Heart Rhythm: 26 Nov 2020; epub ahead of print
Berisso MZ, Martignani C, Ammendola E, Narducci ML, ... Malacrida M, Biffi M
Heart Rhythm: 26 Nov 2020; epub ahead of print | PMID: 33249200
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Impact:
Abstract

Sex differences in arrhythmic burden with the wearable cardioverter-defibrillator.

Goldenberg I, Erath JW, Russo AM, Burch AE, ... McNitt S, Kutyifa V
Background
Data on the arrhythmic burden of women at risk for sudden cardiac death are limited, especially in patients using the wearable cardioverter-defibrillator (WCD).
Objective
We aimed to characterize WCD compliance, atrial and ventricular arrhythmic burden, and WCD outcomes by sex in patients enrolled in the WEARIT-II U.S. Registry.
Methods
In the WEARIT-II Registry, we stratified 2000 patients by sex into women (n = 598) and men (n = 1402). WCD wear time, ventricular and atrial arrhythmia events during WCD use, and implantable cardioverter-defibrillator (ICD) implantation rates at the end of WCD use were evaluated.
Results
The mean WCD wear time was similar in women and men (94 days vs 90 days; P = .145), with longer daily use in women (21.4 h/d vs 20.7 h/d; P = .001). Burden of ventricular tachycardia or ventricular fibrillation was higher in women, with 30 events per 100 patient-years compared with 18 events per 100 patient-years in men (P = .017), with similar findings for treated and non-treated ventricular tachycardia/ventricular fibrillation. Recurrent atrial arrhythmias/sustained ventricular tachycardia was also more frequent in women than in men (167 events per 100 patient-years vs 73 events per 100 patient-years; P = .042). However, ICD implantation rate at the end of WCD use was similar in both women and men (41% vs 39%; P = .448).
Conclusion
In the WEARIT-II Registry, we have shown a higher burden of ventricular and atrial arrhythmia events in women than in men. ICD implantation rates at the end of WCD use were similar. Our findings warrant monitoring women at risk for sudden cardiac death who have a high burden of atrial and ventricular arrhythmias while using the WCD.

Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Heart Rhythm: 25 Nov 2020; epub ahead of print
Goldenberg I, Erath JW, Russo AM, Burch AE, ... McNitt S, Kutyifa V
Heart Rhythm: 25 Nov 2020; epub ahead of print | PMID: 33248269
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Impact:
Abstract

Predictive value of atrial fibrillation during the postradiofrequency ablation blanking period.

Calkins H, Gache L, Frame D, Boo LM, ... Duytschaever M, Packer DL
Background
Recurrent arrhythmia following catheter ablation of atrial fibrillation (AF) may present early, during a standard 3-month blanking period. Early recurrence has been correlated to late recurrence, but the degree to which its absence predicts longer-term success has not been quantified.
Objective
The purpose of this study was to explore and quantify the relationship between early and late arrhythmia recurrence, specifically the negative predictive value, that is, the degree to which absence of blanking period recurrence predicts absence of late recurrence.
Methods
A systematic literature review and meta-analysis were conducted using statistical methods of a diagnostic test accuracy review. Studies of AF ablation using point-by-point radiofrequency, with repeated monitoring of arrhythmia recurrence including asymptomatic recurrence, and with separate data by AF type, were eligible.
Results
Nine studies met the prespecified eligibility criteria. For paroxysmal AF, 89% (confidence interval [CI] 82%-94%) of patients free from early recurrence remained free from late recurrence. The estimate for persistent AF was similar (91%; CI 75%-97%). This finding was robust in sensitivity analyses. Patients with early recurrence had a wider range of likely outcomes with longer-term follow-up.
Conclusion
Freedom from AF recurrence during the blanking period is highly predictive of longer-term success in catheter ablation. Clinical trials in this area may be able to leverage these findings to more quickly assess the potential utility of new ablation technologies and methods, for example, by using early surrogate measures of success.

Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Heart Rhythm: 23 Nov 2020; epub ahead of print
Calkins H, Gache L, Frame D, Boo LM, ... Duytschaever M, Packer DL
Heart Rhythm: 23 Nov 2020; epub ahead of print | PMID: 33242668
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Impact:
Abstract

The frequency spectrum of sympathetic nerve activity and arrhythmogenicity in ambulatory dogs.

Liu X, Yuan Y, Wong J, Meng G, ... Everett TH, Chen PS
Background
Sympathetic nerve activity, heart rate (HR), and blood pressure (BP) all have very low frequency (VLF), low frequency (LF), and high frequency (HF) oscillations.
Objective
The purpose of this study was to test the hypothesis that the frequency spectra of subcutaneous nerve activity (ScNA), stellate ganglion nerve activity (SGNA), HR, and BP are important to cardiac arrhythmogenesis.
Methods
We used radiotransmitters to record SGNA, ScNA, HR, and BP in 6 ambulatory dogs and determined the dominant frequency and paroxysmal atrial tachyarrhythmia (PAT) episodes in 3-minute windows over a 24-hour period.
Results
The frequency spectra determined in ScNA reflected that in SGNA. HF oscillations were present in both ScNA and SGNA at all time but could be overshadowed by the much larger LF and VLF burst activities. The dominant frequency could occur in any of the 3 frequency bands. There were circadian variations with more frequent occurrences of HF oscillations at night. HF oscillations in HR and BP matched HF oscillations in SGNA and ScNA. PATs occurred only when dominant frequencies of SGNA and ScNA were in the LF and VLF bands.
Conclusion
HF oscillations in BP and HR correlate with HF oscillations in sympathetic nerve activity and are present at all time. HF oscillations can be overshadowed by the much larger LF and VLF burst activities. PATs occur only when LF or VLF, but not when HF, is the dominant frequency. The frequency spectra determined in ScNA reflect that in SGNA.

Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Heart Rhythm: 23 Nov 2020; epub ahead of print
Liu X, Yuan Y, Wong J, Meng G, ... Everett TH, Chen PS
Heart Rhythm: 23 Nov 2020; epub ahead of print | PMID: 33246037
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Impact:
Abstract

Current strategies to minimize postoperative hematoma formation in patients undergoing cardiac implantable electronic device implantation: A review.

Mehta N, Doerr K, Skipper A, Rojas-Pena E, Dixon S, Haines D

There are an increasing number of cardiac electronic device implants and generator changes with a longer patient life expectancy along with concomitant increase in antiplatelet and anticoagulant regimens, which can increase the incidence of pocket hematomas. We have conducted an in-depth analysis on the relevant literature, which is rife with varying definition of hematomas, on ways to reduce pocket hematomas. We have analyzed studies on periprocedural medication management, intraprocedural use of prohemostatic agents, and postprocedure role of compression devices.

Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Heart Rhythm: 22 Nov 2020; epub ahead of print
Mehta N, Doerr K, Skipper A, Rojas-Pena E, Dixon S, Haines D
Heart Rhythm: 22 Nov 2020; epub ahead of print | PMID: 33242669
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Impact:
Abstract

Reassessing the role of antitachycardia pacing in fast ventricular arrhythmias in primary prevention implantable cardioverter-defibrillator recipients: Results from MADIT-RIT.

Schuger C, Daubert JP, Zareba W, Rosero S, ... McNitt S, Kutyifa V
Background
In Multicenter Automatic Defibrillator Implantation Trial - Reduce Inappropriate Therapy (MADIT-RIT), high-rate cutoff (arm B) and delayed therapy (arm C) reduced the risk of inappropriate implantable cardioverter-defibrillator (ICD) interventions when compared with conventional programming (arm A); however, appropriate but unnecessary therapies were not evaluated.
Objective
The purpose of this study was to assess the value of antitachycardia pacing (ATP) for fast ventricular arrhythmias (VAs) ≥ 200 beats/min in patients with primary prevention ICD.
Methods
We compared ATP only, ATP and shock, and shock only rates in patients in MADIT-RIT treated for VA ≥ 200 beats/min. The only difference between these randomized groups was the time delay between ventricular tachycardia detection and therapy (3.4 seconds vs 4.9 seconds vs 14.4 seconds).
Results
In arm A, 11.5% patients had events, the initial therapy was ATP in 10.5% and shock in 1%, and the final therapy was ATP in 8% and shock in 3.5%. In arm B, 6.6% had events, 4.2% were initially treated with ATP and 2.4% with shock, and the final therapy was ATP in 2.8% and shock in 3.8%. In arm C, 4.7% had events, 2.5% were initially treated with ATP and 2.3% with shock, and the final therapy was ATP in 1.4% and shock in 3.3%. The final shock rate was similar in arm A vs arm B (3.5% vs 3.8%; P = .800) and in arm A vs arm C (3.5% vs 3.3%; P = .855) despite the marked discrepancy in initial ATP therapy utilization.
Conclusion
In MADIT-RIT, there was a significant reduction in ATP interventions with therapy delays due to spontaneous termination, with no difference in shock therapies, suggesting that earlier interventions for VA ≥ 200 beats/min are likely unnecessary, leading to an overestimation of the value of ATP in primary prevention ICD recipients.

Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Heart Rhythm: 20 Nov 2020; epub ahead of print
Schuger C, Daubert JP, Zareba W, Rosero S, ... McNitt S, Kutyifa V
Heart Rhythm: 20 Nov 2020; epub ahead of print | PMID: 33232811
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Impact:
Abstract

Electrophysiological effects of ranolazine in a goat model of lone atrial fibrillation.

Opačić D, van Hunnik A, Zeemering S, Dhalla A, ... Schotten U, Verheule S
Background
There is still an unmet need for pharmacologic treatment of atrial fibrillation (AF) with few effects on ventricular electrophysiology. Ranolazine is an antiarrhythmic drug reported to have strong atrial selectivity.
Objective
The purpose of this study was to investigate the electrophysiological effects of ranolazine in atria with AF-induced electrical remodeling in a model of lone AF in awake goats.
Methods
Electrode patches were implanted on the atrial epicardium of 8 Dutch milk goats. Experiments were performed at baseline and after 2 and 14 days of electrically maintained AF. Several electrophysiological parameters and AF episode duration were measured during infusion of vehicle and different doses of ranolazine (target plasma levels 4, 8, and 16 μM, respectively).
Results
The highest dose of ranolazine significantly prolonged atrial effective refractory period and decreased atrial conduction velocity at baseline and after 2 days of AF. After 2 weeks of AF, ranolazine prolonged the p5 and p50 of AF cycle length distribution in a dose-dependent manner but was not effective in restoring sinus rhythm. No adverse ventricular arrhythmic events (eg, premature ventricular beats or signs of hemodynamic instability) were observed during infusion of ranolazine at any point in the study.
Conclusion
The lowest investigated dose of ranolazine, which is expected to block both late I and atrial peak I, had no effect on the investigated electrophysiological parameters. The highest dose affected both atrial and ventricular electrophysiological parameters at different stages of AF-induced remodeling but was not efficacious in cardioverting AF to sinus rhythm in a goat model of lone AF.

Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Heart Rhythm: 20 Nov 2020; epub ahead of print
Opačić D, van Hunnik A, Zeemering S, Dhalla A, ... Schotten U, Verheule S
Heart Rhythm: 20 Nov 2020; epub ahead of print | PMID: 33232809
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Impact:
Abstract

Subcutaneous versus transvenous implantable defibrillator: An updated meta-analysis.

Rordorf R, Casula M, Pezza L, Fortuni F, ... Savastano S, Vicentini A
Background
Implantable cardioverter-defibrillator (ICD) placement is a well-established therapy for prevention of sudden cardiac death. The subcutaneous implantable cardioverter-defibrillator (S-ICD) was specifically designed to overcome some of the complications related to the transvenous implantable cardioverter-defibrillator (TV-ICD), such as lead complications and systemic infections. Evidence on the comparison of S-ICD vs TV-ICD are limited.
Objective
The purpose of this study was to conduct an updated meta-analysis comparing S-ICD vs TV-ICD.
Methods
Electronic databases were searched for studies directly comparing clinical outcomes and complications between S-ICD and TV-ICD. The primary outcome was the composite of clinically relevant complications (lead, pocket, major procedural complications; device-related infections) and inappropriate shocks. Secondary outcomes included death and the individual components of the primary outcome.
Results
Thirteen studies comprising 9073 patients were included in the analysis. Mean left ventricular ejection fraction was 40% ± 10%; 30% of patients were female; and 73% had an ICD implanted for primary prevention. There was no statistically significant difference in the risk of the primary outcome between S-ICD and TV-ICD (odds ratio [OR] 0.80; 95% confidence interval [CI] 0.53-1.19). Patients with S-ICD had lower risk of lead complications (OR 0.14; 95% CI 0.06-0.29; P <.00001) and major procedural complications (OR 0.18; 95% CI 0.06-0.57; P = .003) but higher risk of pocket complications (OR 2.18; 95% CI 1.30-3.66; P = .003) compared to those with TV-ICD. No significant differences were found for the other outcomes.
Conclusion
In patients with an indication for ICD without the need for pacing, TV-ICD and S-ICD are overall comparable in terms of the composite of clinically relevant device-related complications and inappropriate shock.

Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Heart Rhythm: 15 Nov 2020; epub ahead of print
Rordorf R, Casula M, Pezza L, Fortuni F, ... Savastano S, Vicentini A
Heart Rhythm: 15 Nov 2020; epub ahead of print | PMID: 33212250
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Impact:
Abstract

Impact of myocardial fiber orientation on lesions created by a novel heated saline-enhanced radiofrequency needle-tip catheter: An MRI lesion validation study.

Suzuki A, Lehmann HI, Wang S, Monahan KH, ... Curley MG, Packer DL
Background
Irrigated needle catheter ablation is efficacious for creation of transmural lesions in the left ventricle (LV). However, interdependence of needle orientation and myocardial fiber orientation and the resulting influence on lesion creation remain unclear.
Objective
The purpose of this study was to investigate the impact of myocardial fiber orientation on reproducibility and controllability of lesion creation in LV myocardium using a heated saline-enhanced radiofrequency (SERF) needle-tip catheter system.
Methods
Eleven dogs underwent catheter ablation using this novel catheter. Ablative lesions were created using different power and ablation times (15-50 W; application 25-120 seconds; 60°C irrigation saline at 10 mL/min). Hearts were explanted, and lesions were evaluated using 3-T cardiac magnetic resonance (CMR), gross pathologic, and histologic investigations.
Results
Forty-three of 57 lesions (75.4%) were transmural, and lesion depth reached approximately 90% of LV wall thickness. Lesion volume in both gross pathology and ex vivo CMR showed a positive linear correlation with power × radiofrequency (RF) time index (r = 0.637, P <.001; and r = 0.786, P <.001, respectively). Maximum width (circumferential direction of LV) and maximum length (long-axis direction) of all lesions were distributed in the middle layer of LV where myocardium runs circumferentially. Paired-sample Student t test showed maximum lesion width was significantly greater than maximum lesion length by both CMR and gross pathologic evaluation (26.1 ± 9.6 mm vs 17.2 ± 6.7 mm, P <.001; and 22.5 ± 7.7 mm vs 18.6 ± 5.9 mm, P <.001, respectively).
Conclusion
This catheter showed feasibility in creating transmural LV lesions. Power × RF time index was strongly correlated with lesion volume and predicted lesion size. More importantly, SERF lesions extended along the myocardial fiber orientation.

Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Heart Rhythm: 15 Nov 2020; epub ahead of print
Suzuki A, Lehmann HI, Wang S, Monahan KH, ... Curley MG, Packer DL
Heart Rhythm: 15 Nov 2020; epub ahead of print | PMID: 33212248
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Impact:
Abstract

Epicardial course of the septopulmonary bundle: Anatomical considerations and clinical implications for roofline completion.

Pambrun T, Duchateau J, Delgove A, Denis A, ... Walton RD, Derval N
Background
Gaps in the roofline have been ascribed to epicardial conduction using the septopulmonary bundle.
Objectives
We sought to evaluate the frequency of septopulmonary bundle bypass during roofline ablation, to describe anatomical conditions favoring this epicardial gap, and to propose an alternative strategy when present.
Methods
One hundred consecutive patients underwent atrial fibrillation ablation. A de novo roofline was created between the superior pulmonary veins. In cases of residual gaps, a floor line was created between the inferior pulmonary veins. Microtomography imaging and histological analyses of 5 human donor hearts were performed: a specific focus was made on the dome and the posterior wall.
Results
Residual gaps were more frequent in rooflines than floor lines (33% vs 15%; P = .049). Electrogram morphologies, activation sequences, and pacing maneuvers indicated an epicardial bypass of the roofline in all cases. Conduction block was obtained in 67 roof lines and 28 floor lines, resulting in a 95% success rate of linear block, without \"box\" isolation. Between the superior pulmonary veins, the atrial myocardium was thicker and consistently displayed adipose tissue separating the septopulmonary bundle from the septoatrial bundle.
Conclusion
Epicardial conduction across the roofline is common and requires careful electrogram analysis to detect. In such cases, a floor line can be an effective alternative strategy, with clear validation criteria. Myocardial thickness and fat interposition may explain difficulties in achieving lesion transmurality during roofline ablation.

Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Heart Rhythm: 10 Nov 2020; epub ahead of print
Pambrun T, Duchateau J, Delgove A, Denis A, ... Walton RD, Derval N
Heart Rhythm: 10 Nov 2020; epub ahead of print | PMID: 33188900
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Impact:
Abstract

Catheter ablation of atrial fibrillation using ablation index-guided high power (50 W) for pulmonary vein isolation with or without esophageal temperature probe (the AI-HP ESO II).

Chen S, Schmidt B, Seeger A, Bordignon S, ... Kreuzer C, Chun KRJ
Background
High-power, short-duration ablation for pulmonary vein isolation (PVI) in the treatment of atrial fibrillation (AF) facilitates the procedure and improve effectiveness; however, esophageal injury remains a safety concern.
Objective
The purpose of this study was to investigate the role of luminal esophageal temperature (LET) monitoring during high-power ablation for PVI in terms of endoscopic esophageal lesion.
Methods
Patients with symptomatic AF underwent ablation index-guided high-power (AI-HP) PVI (50 W; AI anterior wall/posterior wall: 550/400). In the first consecutive set of patients, an insulated esophageal temperature probe was used for LET monitoring (cutoff LET >39°C) (group A). In the second consecutive set of patients, the probe was not used (group B). All patients were scheduled to undergo esophageal endoscopy 1-3 days after ablation.
Results
A total of 120 patients (60 group A; 60 group B) were included in the study (mean age 67.8 years; 64% male). Baseline characteristics and procedural outcomes were similar between the 2 groups. Procedural PVI was achieved in all patients. First-pass PVI rate was 96.6%. Mean procedural radiofrequency (RF) time was 11.5 minutes, mean procedural time was 55.5 minutes, and fluoroscopic time was 5.6 minutes. Mean contact force at the LA posterior wall was 23 g, and mean RF ablation time at the LA posterior wall was 3.2 minutes. Two patients in group A and 1 patient in group B had endoscopic small esophageal lesions (P = .99). No serious procedural adverse events were observed.
Conclusion
Among patients undergoing AI-HP (50 W) PVI, the incidences of ablation-related endoscopic esophageal lesion in patients with and those without use of a temperature probe for LET monitoring (cutoff 39°C) were comparably low.

Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Heart Rhythm: 30 Oct 2020; 17:1833-1840
Chen S, Schmidt B, Seeger A, Bordignon S, ... Kreuzer C, Chun KRJ
Heart Rhythm: 30 Oct 2020; 17:1833-1840 | PMID: 32470628
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Impact:
Abstract

Biophysical properties, efficacy, and lesion characteristics of a new linear cryoablation catheter in a canine model.

Suzuki A, Lehmann HI, Wang S, Parker KD, ... Monahan KH, Packer DL
Background
The cryoballoon (CB) catheter is an established tool for pulmonary vein isolation (PVI), but its use is limited for that purpose.
Objective
The purpose of this study was to investigate the biophysical properties of a newly developed linear cryoablation catheter for creation of linear ablation lesions in an in vivo model.
Methods
Twenty-nine dogs (14 acutely ablated, 15 chronically followed) underwent cryoablation using the linear cryoablation catheter. Regions of interest included the cavotricuspid isthmus (CTI), mitral isthmus (MI), left atrial (LA) roof, and LA posterior wall in an acute study. Cryoablations for CTI and MI were performed in 14 atrial fibrillation animals after PVI and followed over 1 month in the chronic study. Tissue temperature during cryoablation was monitored using implanted thermocouples in the regions of interest. Gross and microscopic pathologic characteristics of the lesions were assessed.
Results
In acute animals, lesion length (transmurality) was CTI 34 ± 4 mm (89% ± 11%); MI 29 ± 4 mm (90% ± 13%); LA roof 19 ± 3 mm (90% ± 8%); and LA posterior wall 19 ± 2 mm (81% ± 13%), with 1 or 2 freezes. Chronic bidirectional block was achieved in 13 of 14 CTI (93%) and 10 of 14 MI (71%) ablations after 1-month follow-up and was consistent with lesion continuity and transmurality upon pathology. The lowest tissue temperature correlated well with the closest distance to the linear cryocatheter (r = 0.688; P <.001).
Conclusion
This linear cryocatheter created continuous and transmural linear lesions with \"single-shot\" cryoenergy application and has the potential for clinical use in the setting of various arrhythmias.

Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Heart Rhythm: 30 Oct 2020; 17:1967-1975
Suzuki A, Lehmann HI, Wang S, Parker KD, ... Monahan KH, Packer DL
Heart Rhythm: 30 Oct 2020; 17:1967-1975 | PMID: 32470624
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Impact:
Abstract

Clinical impact of left ventricular paced conduction disturbance in cardiac resynchronization therapy.

Ueda N, Noda T, Nakajima I, Ishibashi K, ... Yasuda S, Kusano K
Background
Myocardial scarring is associated with nonresponse to cardiac resynchronization therapy (CRT) and conduction delay. Little is known about the significance and cause of left ventricular (LV) paced conduction disturbance (LPCD).
Objective
The purpose of this study was to investigate the clinical impact of paced interlead electrical delay and the difference in each conduction time from LV pace to right ventricular (RV) sense (LVp-RVs) and from RV pace to LV sense (RVp-LVs) [(LVp-RVs) - (RVp-LVs)], in CRT.
Methods
Among 137 patients who underwent CRT implantation, LVp-RVs and RVp-LVs were measured intraoperatively. The relationships between [(LVp-RVs) - (RVp-LVs)] and perfusion defects on myocardial perfusion single photon emission computed tomography (SPECT) imaging or [(LVp-RVs) - (RVp-LVs)] and clinical outcomes were assessed.
Results
After CRT implantation, 81 patients (59%) responded to CRT. [(LVp-RVs) - (RVp-LVs)] was significantly longer in nonresponders than in responders (9.7 ± 47.3 ms vs -4.5 ± 33.2 ms; P = .041). Patients with LPCD [(LVp-RVs) > (RVp-LVs)] had higher perfusion defects in the anterolateral region (2.7 ± 2.7 vs 1.1 ± 1.6; P = .0015) on SPECT. Multivariate analysis showed that LPCD was the independent predictor of nonresponse to CRT (odds ratio 0.40; 95% confidence interval [CI] 0.17-0.90; P = .026). During median follow-up of 2.3 years (interquartile range 1.3-5.5), LPCD was the independent predictor of cardiac death and/or heart failure hospitalization in multivariate analysis (hazard ratio 2.04; 95% CI 1.19-3.55; P = .010).
Conclusion
LPCD could predict nonresponse to CRT and poor outcome. Further intervention, such as adjustment of pacing timing or multipoint/site pacing, may be needed in such patients.

Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Heart Rhythm: 30 Oct 2020; 17:1870-1877
Ueda N, Noda T, Nakajima I, Ishibashi K, ... Yasuda S, Kusano K
Heart Rhythm: 30 Oct 2020; 17:1870-1877 | PMID: 32470623
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Impact:
Abstract

Preimplantation interlead ECG heterogeneity is superior to QRS complex duration in predicting mechanical super-response in patients with non-left bundle branch block receiving cardiac resynchronization therapy.

Bortolotto AL, Verrier RL, Nearing BD, Marum AA, ... Zimetbaum PJ, Chang JD
Background
Reliable quantitative preimplantation predictors of response to cardiac resynchronization therapy (CRT) are needed.
Objective
We tested the utility of preimplantation R-wave and T-wave heterogeneity (RWH and TWH, respectively) compared to standard QRS complex duration in identifying mechanical super-responders to CRT and mortality risk.
Methods
We analyzed resting 12-lead electrocardiographic recordings from all 155 patients who received CRT devices between 2006 and 2018 at our institution and met class I and IIA American College of Cardiology/American Heart Association/Heart Rhythm Society guidelines with echocardiograms before and after implantation. Super-responders (n=35, 23%) had ≥20% increase in left ventricular ejection fraction and/or ≥20% decrease in left ventricular end-systolic diameter and were compared with non-super-responders (n=120, 77%), who did not meet these criteria. RWH and TWH were measured using second central moment analysis.
Results
Among patients with non-left bundle branch block (LBBB), preimplantation RWH was significantly lower in super-responders than in non-super-responders in 3 of 4 lead sets (P=.001 to P=.038) and TWH in 2 lead sets (both, P=.05), with the corresponding areas under the curve (RWH: 0.810-0.891, P<.001; TWH: 0.759-0.810, P≤.005). No differences were observed in the LBBB group. Preimplantation QRS complex duration also did not differ between super-responders and non-super-responders among patients with (P=.856) or without (P=.724) LBBB; the areas under the curve were nonsignificant (both, P=.69). RWH ≥ 420 μV predicted 3-year all-cause mortality in the entire cohort (P=.037), with a hazard ratio of 7.440 (95% confidence interval 1.015-54.527; P=.048); QRS complex duration ≥ 150 ms did not predict mortality (P=.27).
Conclusion
Preimplantation interlead electrocardiographic heterogeneity but not QRS complex duration predicts mechanical super-response to CRT in patients with non-LBBB.

Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Heart Rhythm: 30 Oct 2020; 17:1887-1896
Bortolotto AL, Verrier RL, Nearing BD, Marum AA, ... Zimetbaum PJ, Chang JD
Heart Rhythm: 30 Oct 2020; 17:1887-1896 | PMID: 32497764
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Impact:
Abstract

Comparison of left ventricular lead upgrade vs continued medical care among patients eligible for cardiac resynchronization therapy at the time of defibrillator generator replacement: Predictors of left ventricular lead upgrade and associations with long-term outcomes.

Hyman MC, Bao H, Curtis JP, Minges K, ... Marchlinski FE, Hsu JC
Background
Randomized trials evaluating cardiac resynchronization therapy (CRT) have excluded patients with a pre-existing implantable cardioverter-defibrillator (ICD). The association of CRT upgrade with clinical outcomes in patients with a pre-existing ICD is unclear.
Objective
The purpose of this study was to examine a CRT-eligible population to evaluate clinical outcomes associated with CRT upgrade compared to patients who did not undergo CRT.
Methods
Using the National Cardiovascular Data Registry (NCDR) ICD Registry between April 2010 and December 2014, we created a hierarchical logistic regression model to identify predictors of CRT upgrade in a CRT-eligible ICD population. In the subpopulation of patients with Medicare-linked claims data, differential outcomes were determined with censoring at 3 years. The primary endpoint of this study was all-cause mortality, with secondary endpoints of rates of hospitalization and procedural complications.
Results
CRT upgrade was performed in 75.5% of CRT-eligible patients with pre-existing ICD (n = 15,803). Presence of left bundle branch block conduction was the strongest predictor of CRT upgrade (odds ratio [OR] 4.56; 95% confidence interval [CI] 4.08-5.11; P <.0001). In both unadjusted and adjusted analyses, CRT upgrade was associated with a reduction in mortality at 3 years (unadjusted hazard ratio [HR] 0.80; 95% CI 0.70-0.92; P = .001; adjusted HR 0.84; 95% CI 0.72-0.98; P = .02, respectively). Compared to patients with ICD generator replacement only, patients who underwent CRT upgrade experienced no different 3-year rates of hospitalization (adjusted HR 1.01; 95% CI 0.91-1.12; P = .81) or 1-year periprocedural complication rates (adjusted HR 1.07; 95% CI 0.79-1.45; P = .66).
Conclusion
In a national registry of CRT-eligible patients with pre-existing ICD, upgrade to CRT was associated with lower rates of mortality than continued medical management.

Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Heart Rhythm: 30 Oct 2020; 17:1878-1886
Hyman MC, Bao H, Curtis JP, Minges K, ... Marchlinski FE, Hsu JC
Heart Rhythm: 30 Oct 2020; 17:1878-1886 | PMID: 32497762
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Impact:
Abstract

Catheter ablation of intra-atrial reentrant/focal atrial tachycardia in adult congenital heart disease: Value of final programmed atrial stimulation.

Waldmann V, Amet D, Zhao A, Ladouceur M, ... Iserin L, Marijon E
Background
While outcomes of intra-atrial reentrant/focal atrial tachycardia (IART/FAT) catheter ablation have considerably improved in adult congenital heart disease (ACHD), recurrences remain common with different circuits frequently encountered.
Objective
We aimed to assess the value of programmed atrial stimulation after successful clinical IART/FAT catheter ablation in patients with ACHD.
Methods
This is a retrospective study including all patients with ACHD undergoing IART/FAT catheter ablation in a tertiary center. After successful catheter ablation of clinical arrhythmia, survival free from arrhythmia recurrence was analyzed according to whether all inducible IARTs/FATs were targeted.
Results
From 2004 to 2020, 238 IART/FAT catheter ablation procedures were performed (mean age 44.1 ± 15.0 years; 61.3% men). Acute procedural success of clinical arrhythmia was achieved in 208 procedures (87.4%). Among 122 procedures with programmed atrial stimulation (58.7%), at least 1 other IART/FAT was induced in 61 patients (50%). All inducible IARTs/FATs were ablated in 54 patients (88.5%), whereas 7 patients (11.5%) presented with at least 1 nontargeted inducible IART/FAT. Patients with nontargeted inducible IART/FAT had a higher risk of atrial arrhythmia episodes than did inducible patients treated with ablation of all IARTs/FATs (hazard ratio 5.7; 95% confidence interval 1.7-18.4; P = .004), with 12-month atrial arrhythmias recurrence rates of 22.9% and 77.7%, respectively. Inducible patients with successful ablation of all IARTs/FATs had a risk of recurrence similar to that of noninducible patients (hazard ratio 0.6; 95% confidence interval 0.3-1.3; P = .215).
Conclusion
Beyond clinical IART/FAT catheter ablation in patients with ACHD, our findings suggest the interest of systematically targeting all remaining inducible arrhythmias, irrespective of whether previously documented.

Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Heart Rhythm: 30 Oct 2020; 17:1953-1959
Waldmann V, Amet D, Zhao A, Ladouceur M, ... Iserin L, Marijon E
Heart Rhythm: 30 Oct 2020; 17:1953-1959 | PMID: 32512179
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Impact:
Abstract

Management and long-term outcomes associated with recalled implantable cardioverter-defibrillator leads: A multicenter experience.

Mar PL, John A, Kumar S, Barry N, ... Lakkireddy D, Gopinathannair R
Background
No comparative study of outcomes in Riata and Sprint Fidelis leads undergoing lead extraction (LE), lead abandonment (LA), and generator change only (GC) has been published.
Objectives
Determine outcomes (major complications [MC]; death, extended hospitalization, or rehospitalization within 60 days [RH]; lead malfunction) of LE, LA, and GC for recalled leads.
Methods
Retrospective, multicenter, comparative study.
Results
A total of 298 LE, 85 LA, and 310 GC were performed. In the clinical setting of a lead intervention, there was no difference in a composite of MC, death, RH, lead revision, inappropriate shocks, or device infection between LE and LA groups (15% vs 22%, P = .140). In the clinical setting of a device at elective replacement interval (ERI), there were significantly more acute events at 60 days (MC, death, and RH) in the LE and LA groups at 15.4% (4) and 15.4% (4), and this was significantly (P = .017) higher than the GC group at 5.1% (16). There was no difference (P = 1.000) in the composite of MC, death, RH, lead malfunction, lead revisions, device infections, or inappropriate shocks between LE, LA, and GC groups at 15.4% (4), 15.4% (4), and 17.4% (54), respectively. Following generator change, 14 of 175 Fidelis leads and 3 of 135 Riata leads failed over a total of 12,714 months of follow-up.
Conclusions
The failure rate of recalled leads was substantially lower compared to previous reports. It may be prudent to perform generator change only when the device is at ERI, especially when the recalled lead has historical performance that likely outweighs the risks of extraction/abandonment.

Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Heart Rhythm: 30 Oct 2020; 17:1909-1916
Mar PL, John A, Kumar S, Barry N, ... Lakkireddy D, Gopinathannair R
Heart Rhythm: 30 Oct 2020; 17:1909-1916 | PMID: 32512178
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Impact:
Abstract

Transvenous lead extraction in patients with prior extraction procedures: Procedural profiles and outcomes.

Hutt E, Diab M, Wazni OM, Kaur S, ... Wilkoff BL, Hussein AA
Background
Subclinical venous injuries are common during transvenous lead extraction (TLE), but their implications for future TLE are unclear. Little is known about whether a prior TLE adds risk or complexity to subsequent extraction procedures.
Objective
The purpose of this study was to assess procedural profiles and outcomes of TLE based on whether patients had prior extraction procedures.
Methods
All 3258 consecutive patients undergoing TLE at the Cleveland Clinic (1996-2012) were included. Procedural profiles and outcomes were determined.
Results
Of 3258 TLEs, 198 had prior TLE. Median number of leads in place was 2 in both groups, but patients with prior TLE were more likely to have defibrillator leads (47% vs 41%; P = .08) and more likely to be pacemaker-dependent (32% vs 25%; P = .02). The age of oldest lead (median 2134 vs 1902 days; P = .4) and combined age of leads (median 2948 vs 2676 days; P = .6) were comparable. Procedures were longer in those with prior TLE (166 ± 79 minutes vs 149 ± 74 minutes; P = .004) with comparable fluoroscopy times (median 13 vs 11 minutes; P = .07), and successful extraction was more likely to require specialized tools (88% vs 81%; P = .006) with higher likelihood of rescue femoral workstation (12% vs 4%; P <.0001). Clinical success rates were comparable in those with prior TLE (99.5% vs 98.9%; P = .8) with similar major (3.0% vs 1.9%; P = .3) and minor (3.0% vs 3.7%; P = .8) complication rates.
Conclusion
Extraction procedures were more challenging in patients with prior TLE compared to those without prior TLE but with excellent success and low complication rates.

Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Heart Rhythm: 30 Oct 2020; 17:1904-1908
Hutt E, Diab M, Wazni OM, Kaur S, ... Wilkoff BL, Hussein AA
Heart Rhythm: 30 Oct 2020; 17:1904-1908 | PMID: 32512177
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Impact:
Abstract

Long-term percentage of ventricular pacing in patients requiring pacemaker implantation after transcatheter aortic valve replacement: A multicenter 10-year experience.

Baldi E, Compagnone M, Errigo D, Ferlini M, ... De Ferrari GM, Rordorf R
Background
Recent studies suggest that atrioventricular (AV) conduction may recover after pacemaker (PM) implantation following transcatheter aortic valve replacement (TAVR), but little is known about long-term follow-up of such patients.
Objective
The purpose of this study was to evaluate the long-term percentage of right ventricular pacing in patients who underwent TAVR and required PM implantation stratified based on the indication for permanent pacing.
Methods
Retrospective analysis of all consecutive patients who underwent TAVR from February 2008 to August 2019 at 3 centers was performed. Patients already implanted with a PM/implantable cardioverter-defibrillator (ICD) before TAVR, implanted with a cardiac resynchronization therapy device, or implanted >30 days after TAVR were excluded. Eligible patients were divided into 2 groups based on the presence (persistent atrioventricular block [AVB] group) or absence (nonpersistent AVB group) of persistent third-degree AVB after TAVR.
Results
A total of 1594 patients underwent TAVR. Two hundred four patients were implanted with a PM or ICD after TAVR and 32 met exclusion criteria, so 172 patients were eligible (median time TAVR-PM implant 4 days) for a total of 352 follow-up visits analyzed. A significant difference in the percentage of ventricular pacing was observed at follow-up performed 7-90 days after implantation (98% persistent AVB group vs 8% nonpersistent AVB group; P <.001). This difference remained significant at follow-up performed 91-270 days (95% vs 3.5%; P <.001), 271-540 days (95.5% vs 3%; P = .006), and 541-900 days (97.4% vs 2.2%; P <.001) after implantation.
Conclusion
Patients requiring PM implantation due to persistent third-degree AVB after TAVR were less likely to show AV conduction recovery, whereas patients implanted for other indications showed a low percentage of pacing during follow-up.

Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Heart Rhythm: 30 Oct 2020; 17:1897-1903
Baldi E, Compagnone M, Errigo D, Ferlini M, ... De Ferrari GM, Rordorf R
Heart Rhythm: 30 Oct 2020; 17:1897-1903 | PMID: 32512176
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Abstract

Trends in utilization and spending on remote monitoring of pacemakers and implantable cardioverter-defibrillators among Medicare beneficiaries.

Holtzman JN, Wadhera RK, Choi E, Zhao T, ... Shen C, Kramer DB
Background
National trends and costs associated with remote and in-office interrogations of pacemakers and implantable cardioverter-defibrillators (ICDs) have not been previously described.
Objective
The purpose of this study was to evaluate utilization and Medicare spending for remote monitoring and in-office interrogations for pacemakers and ICDs.
Methods
We performed a retrospective cohort study of claims and spending for remote and in-office interrogations of pacemakers and ICDs for Medicare fee-for-service beneficiaries from 2012 to 2015. Aggregate and per-beneficiary claims and spending were calculated for each device type.
Results
Among all patients, 41.9% were female and the mean age was 78.3 years. From 2012 to 2015, remote monitoring utilization increased sharply. Aggregate professional remote monitoring claims for pacemakers increased by 61.3% and for ICDs by 5.6%, with an increase in technical claims (combined for pacemakers and ICDs) of 32.8%. Spending on all remote and in-office interrogations for these devices totaled $160 million per year, with remote costs increasing nearly 25% from $45.4 million in 2012 to $56.7 million in 2015. At the beneficiary level, remote interrogations increased for pacemakers from 0.6 to 0.9 per year, and for ICDs from 1.3 to 1.4 per year, whereas in-office interrogations decreased from 2.8 to 2.7 per year and from 3.0 to 2.9 per year, respectively. Beneficiary-level analysis revealed increased expenditures on remote interrogation offset by decreases in in-office expenditures, with total annual spending decreasing by $2 and $5 per beneficiary, respectively.
Conclusion
Remote monitoring utilization increased substantially from 2012 to 2015, whereas annual costs per beneficiary decreased.

Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Heart Rhythm: 30 Oct 2020; 17:1917-1921
Holtzman JN, Wadhera RK, Choi E, Zhao T, ... Shen C, Kramer DB
Heart Rhythm: 30 Oct 2020; 17:1917-1921 | PMID: 32526349
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Impact:
Abstract

Evaluation of mexiletine effect on conduction delay and bradyarrhythmic complications in patients with myotonic dystrophy type 1 over long-term follow-up.

Vio R, Zorzi A, Bello L, Bozzoni V, ... Corrado D, Calore C
Background
Myotonic dystrophy type 1 (DM1) is a multisystemic disorder characterized by progressive cardiac conduction impairment, arrhythmias, and sudden death. Mexiletine is a sodium channel blocker drug used by patients with DM1 for treatment of myotonia, even though definitive proof of its safety over long-term follow-up is lacking.
Objective
The purpose of this study was to assess the impact of mexiletine for treatment of neurological symptoms on the composite endpoint of significant electrocardiogram modification (new onset or worsening of atrioventricular [AV] or intraventricular conduction delay) and bradyarrhythmic complications requiring pacemaker (PM) implantation (advanced AV block, symptomatic sinus pause >3 seconds).
Methods
This retrospective longitudinal study included a series of consecutive patients with genetically confirmed DM1 evaluated at our neurology and cardiology clinics from January 1, 2011, to January 1, 2020, who received mexiletine 200 mg twice daily. Patients with a PM, implantable cardioverter-defibrillator, or severe conduction abnormality (PQ interval ≥230 ms, complete bundle branch block, or atrial fibrillation) at enrollment were excluded.
Results
The study comprised 18 mexiletine-treated patients and 68 mexiletine-free controls. Over median follow-up of 53 months, the endpoint was reached by 4 (22%) mexiletine-treated patients and 23 (33%) non-mexiletine-treated patients (log-rank P = .45). In 3 non-mexiletine-treated patients, bradyarrhythmic complications requiring PM implantation were observed. At univariable analysis, only the presence of mild conduction delay (first-degree AV block with PQ interval <230 ms or left anterior fascicular block) at baseline predicted the endpoint (hazard ratio 2.22; 95% confidence interval 1.04-4.76).
Conclusion
Mexiletine 200 mg twice daily is safe in patients with DM1 and no severe conduction abnormality.

Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Heart Rhythm: 30 Oct 2020; 17:1944-1950
Vio R, Zorzi A, Bello L, Bozzoni V, ... Corrado D, Calore C
Heart Rhythm: 30 Oct 2020; 17:1944-1950 | PMID: 32525073
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