Journal: Heart Rhythm

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Abstract

A NOVEL PATHOGENIC ROLE FOR GALECTIN-3 IN EARLY DISEASE STAGES OF ARRHYTHMOGENIC CARDIOMYOPATHY.

Cason M, Celeghin R, Marinas MB, Beffagna G, ... Basso C, Pilichou K
Background
Arrhythmogenic cardiomyopathy (AC) is a myocardial disease due to desmosomal mutations, whose pathogenesis remains incompletely understood.
Objective
To identify molecular pathways underlying early AC by gene expression profiling in both humans and animal models.
Methods
RNA sequencing for differentially expressed genes (DEGs) was performed on the myocardium of transgenic mice over-expressing the Desmoglein2-N271S mutation before phenotype onset. Zebrafish signaling reporters were used for in vivo validation. Whole exome sequencing was undertaken in 10 genotype-negative AC patients and subsequent direct sequencing in 140 AC index cases.
Results
Among 29 DEGs identified at early disease stages, Lgals3/GAL3 (lectin, galactoside-binding, soluble, 3) showed reduced cardiac expression in transgenic mice and in 3 AC patients who suffered sudden cardiac death without overt structural remodeling. Four rare missense variants of LGALS3 were identified in 5 human AC probands. Pharmacological inhibition of Lgals3 in zebrafish reduced Wnt and TGFβ signaling, increased Hippo/YAP-TAZ signaling, and induced alterations in desmoplakin membrane localization, desmosome integrity and stability. Increased LGALS3 plasma expression in genotype-positive AC patients and CD98 activation supported the GAL3 release by circulating macrophages pointing toward the stabilization of desmosomal assembly at the injured regions.
Conclusions
GAL3 plays a crucial role in early AC onset through regulation of Wnt/β-catenin signaling and intercellular adhesion.

Copyright © 2021. Published by Elsevier Inc.

Heart Rhythm: 11 Apr 2021; epub ahead of print
Cason M, Celeghin R, Marinas MB, Beffagna G, ... Basso C, Pilichou K
Heart Rhythm: 11 Apr 2021; epub ahead of print | PMID: 33857645
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Abstract

Cardiac Potassium Inward Rectifier Kir2: Review of Structure, Regulation, Pharmacology and Arrhythmogenesis.

Reilly L, Eckhardt L
Potassium inward rectifier channel Kir2 is an important component of terminal cardiac repolarization and resting membrane stability. This functionality is part of balanced cardiac excitability and is a defining feature of excitable cardiac membranes. \"Gain\"- or \"loss-of-function\" mutations in KCNJ2, the gene encoding Kir2.1, cause genetic sudden cardiac death syndromes, and loss of Kir2 current, IK1, is a major contributing factor to arrhythmogenesis in failing human hearts. Here we provide a contemporary review of the Kir2 channels\' functional structure, physiology and pharmacology. Beyond the structure and functional relationships, we will focus on the elements of clinically used drugs that block the channel and the implications for treatment of atrial fibrillation with IK1 blocking agents. We will also review the clinical disease entities associated with KCNJ2 mutations and the growing area of research into associated arrhythmia mechanisms. Lastly, Kir2 channels\' presence has become a tipping point for electrical maturity in induced pluripotent stem cell derived cardiomyocytes (iPS-CMs) and highlights the significance of understanding why Kir2 in iPS-CMs is important to consider for CIPA and drug safety testing.

Copyright © 2021. Published by Elsevier Inc.

Heart Rhythm: 11 Apr 2021; epub ahead of print
Reilly L, Eckhardt L
Heart Rhythm: 11 Apr 2021; epub ahead of print | PMID: 33857643
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Abstract

Flecainide-Induced QRS Complex Widening Correlates with Negative Inotropy.

Rabelo Evangelista AB, Monteiro FR, Nearing BD, Belardinelli L, Verrier RL
Background
The negative inotropic effect of Class IC antiarrhythmic drugs limits their use for acute cardioversion of atrial fibrillation (AF).
Objective
In an intact porcine model, we examined effects of pulmonary and intravenous (IV) administration of flecainide on left ventricular (LV) contractility and QRS complex width at doses that are effective in converting new-onset AF to sinus rhythm.
Methods
Flecainide (1.5 mg/kg bolus) was delivered by intratracheal administration and compared to 2.0 mg/kg 10-min IV administration (ESC guideline) and to 0.5 and 1.0 mg/kg 2-min IV doses in 40 closed-chest, anesthetized Yorkshire pigs. Catheters were fluoroscopically positioned in the LV to monitor QRS complex width and contractility and at the bifurcation of the main bronchi to deliver intratracheal flecainide.
Results
Peak flecainide plasma concentrations (Cmax) were similar but the 30-min AUC of plasma levels was 1.4- to 2.9-fold greater for 2.0 mg/kg 10-min IV infusion than for the lower, more rapidly delivered intratracheal and IV doses. The AUC for LV contractility, i.e., negative inotropic burden, was 2.2- to 3.6-fold greater for 2.0 mg/kg 10-min IV dose than for the lower, more rapidly delivered doses. QRS complex widening by flecainide was highly correlated with the decrease in LV contractility (r2=0.890, p<0.0001, for all IV doses; r2=0.812, p=0.014, for intratracheal flecainide).
Conclusions
QRS complex widening in response to flecainide is strongly correlated with the decrease in LV contractility. Rapid pulmonary or IV flecainide delivery reduces the negative inotropic burden while quickly achieving Cmax levels associated with conversion of AF.

Copyright © 2021. Published by Elsevier Inc.

Heart Rhythm: 09 Apr 2021; epub ahead of print
Rabelo Evangelista AB, Monteiro FR, Nearing BD, Belardinelli L, Verrier RL
Heart Rhythm: 09 Apr 2021; epub ahead of print | PMID: 33848647
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Abstract

Cardiac Afferent Signaling Partially Underlies Premature Ventricular Contraction-Induced Cardiomyopathy.

Hori Y, Temma T, Wooten C, Sobowale C, ... Swid M, Ajijola OA
Background
The mechanisms underlying premature ventricular contraction (PVC)-induced cardiomyopathy remain unknown. Transient receptor potential vanilloid 1 (TRPV1) afferent fibers are implicated in the reflex processing of cardiac stress.
Objective
We aimed to determine whether cardiac TRPV1 afferent signaling promote PVC-induced cardiomyopathy.
Methods
A PVC-induced cardiomyopathy swine model (50% PVC burden) was created via an implanted pacemaker. We selectively depleted cardiac TRPV1 afferent fibers using percutaneous epicardial application of Resiniferatoxin (RTX). Animals were randomized to PVC only (n=11), PVC+RTX (n=11), or controls (n=6). We examined early-stage (4 weeks after implantation, n=5) and late-stage PVC-induced cardiomyopathy (8 weeks after implantation, n= 6). At terminal experimentation, animals underwent echocardiography, serum sampling, physiologic, and autonomic reflex testing.
Results
Depletion of cardiac TRPV1 afferents by RTX treatment was confirmed by absent sensory fibers, and absent functional responses to TRPV1 activators. LVEF was worse in late-stage PVC-induced cardiomyopathy than early stage (p< 0.01). At 4 weeks (early stage), LVEF was higher in PVC+RTX vs. PVC animals (51.7 ± 1.6% vs. 45.0 ± 2.1%, p= 0.030), while no significant difference between PVC and PVC+RTX was observed at 8 weeks (late stage). Histologic studies demonstrated reduced fibrosis in PVC+RTX vs PVC alone at 4 weeks (2.27 ± 0.14% vs. 3.01 ± 0.21%, p= 0.020), suggesting that RTX mitigated pro-fibrotic pathways induced by persistent PVCs.
Conclusion
TRPV1 afferent depletion alleviates LV dysfunction in early, but not late stage PVC-induced cardiomyopathy. This temporal effect suggests that multiple pathways promote PVC-induced cardiomyopathy, of which TRPV1 afferents are a part.

Copyright © 2021. Published by Elsevier Inc.

Heart Rhythm: 08 Apr 2021; epub ahead of print
Hori Y, Temma T, Wooten C, Sobowale C, ... Swid M, Ajijola OA
Heart Rhythm: 08 Apr 2021; epub ahead of print | PMID: 33845214
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Abstract

Electrical Storm in Patients with Left Ventricular Assist Devices: Risk Factors, Incidence, and Impact on Survival.

Rehorn MR, Black-Maier E, Loungani R, Sen S, ... Daubert JP, Piccini JP
Background
Ventricular arrhythmias (VAs) and electrical storm (ES) are recognized complications following left ventricular assist device (LVAD) implantation, although their association with long term outcomes remains poorly understood.
Objective
To describe the clinical impact of ES in a population of patients undergoing LVAD implantation at a quaternary care center in the United States.
Methods
This was an observational retrospective study of patients undergoing LVAD implantation from 2009 to 2020 at Duke University Hospital. The incidence of ES (≥3 sustained VA episodes over a 24-hour period without an identifiable reversible cause) was determined from patient records. Risk factors for ES were identified using multivariable Cox proportional hazards modeling.
Results
Among 730 patients undergoing LVAD implant, 78 (10.7%) developed ES at a median of 269 (interquartile range [IQR] 7-766) days following surgery. Twenty-seven patients (34.6%) developed ES within 30 days while 51 (65.4%) presented with ES a median 639 (IQR 281-1,017) days after implant. Following ES, 41% of patients died within one-year. Patients developing ES were more likely to have a history of VAs, VT ablation, antiarrhythmic drug use, and perioperative mechanical circulatory support around the time of LVAD implant compared with patients without ES.
Conclusions
Electrical storm occurs in 1 in 10 patients after LVAD and is associated with higher mortality. Risk factors for ES include a history of VAs, VT ablation, antiarrhythmic drug use, and perioperative mechanical circulatory support. Optimal management of ES surrounding LVAD implant, including escalation of medical therapy, catheter ablation, or adjunctive sympatholytic therapies remains uncertain.

Copyright © 2021. Published by Elsevier Inc.

Heart Rhythm: 07 Apr 2021; epub ahead of print
Rehorn MR, Black-Maier E, Loungani R, Sen S, ... Daubert JP, Piccini JP
Heart Rhythm: 07 Apr 2021; epub ahead of print | PMID: 33839327
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Abstract

Validation of an Algorithm for Continuous Monitoring of Atrial Fibrillation Using a Consumer Smartwatch.

Avram R, Ramsis M, Cristal AD, Nathan V, ... Mortara D, Olgin JE
Background
Consumer devices with broad reach may be useful for screening for atrial fibrillation (AF) in appropriate populations. However, currently there are no consumer devices capable of continuous monitoring for AF.
Objective
To estimate the sensitivity and specificity of a smartwatch algorithm for continuous detection of AF from sinus rhythm in a free-living setting.
Methods
We studied a commercially available smartwatch with photoplethysmography (W-PPG) and electrocardiogram capabilities (W-ECG). We validated a novel W-PPG algorithm combined with a W-ECG algorithm in a free-living setting, comparing the results to a 28-day continuous ECG patch (P-ECG).
Results
A total of 204 participants completed the free-living study, recording 81,944 hours with both P-ECG and smartwatch measurements. We found a sensitivity of 87.8% (95% confidence interval: 83.6-91.0%) and a specificity of 97.4% (97.1-97.7%) for the W-PPG algorithm (every 5-minute classification), a sensitivity of 98.9% (98.1-99.4%) and a specificity of 99.3% (99.1-99.5%) of the W-ECG algorithm and a sensitivity of 96.9% (93.7%-98.5%) and a specificity of 99.3% (98.4-99.7%) for W-PPG triggered W-ECG with a single W-ECG required for confirmation of AF. We found a very strong correlation of W-PPG in quantifying AF Burden when compared to P-ECG (r = 0.98).
Conclusions
Our findings demonstrate that a novel algorithm using a commercially available smartwatch can continuously detect AF with excellent performance and that confirmation with a W-ECG further enhances specificity. Furthermore our W-PPG algorithm can estimate AF burden. Further research is needed to determine whether this is useful in screening for AF in select at-risk patients.

Copyright © 2021. Published by Elsevier Inc.

Heart Rhythm: 06 Apr 2021; epub ahead of print
Avram R, Ramsis M, Cristal AD, Nathan V, ... Mortara D, Olgin JE
Heart Rhythm: 06 Apr 2021; epub ahead of print | PMID: 33838317
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Abstract

Sporadic High Pacing and Shock Impedance at Remote Monitoring in Hybrid Implantable Cardioverter Defibrillators Systems: Clinical Impact and Management.

Pignalberi C, Mariani MV, Castro A, Piro A, ... Fedele F, Lavalle C
Background
Sporadic high impedance values without other anomalies have been recently described by remote monitoring for hybrid cardiac implantable electronic device (CIED) systems. The clinical significance and related hazard of this phenomenon are not fully understood.
Objective
To describe prevalence, management and outcomes associated with hybrid implantable cardioverter defibrillator (ICD) systems.
Methods
We collected data about patients with sporadic high lead impedance alert on remote monitoring, implanted between January 2015 and December 2019 with hybrid ICD system. Pacing thresholds, sensing and impedance values, alongside temporal pattern of impedance values, were collected by remote monitoring, at implantation and during in-office visit.
Results
Among 92 patients receiving hybrid ICDs, 15 (16.3%) had high impedance alert at remote monitoring, 14 Boston Scientific and 1 St. Jude Medical ICD canisters paired with Medtronic or Biotronik DF-1 leads. Four patients had a cardiac resynchronization therapy defibrillator (CRT-D), 7 patients had dual-chamber ICD and 4 patients single-chamber ICD. Three patients presented high atrial lead impedance, 7 patients high right ventricular lead impedance, 1 patient high left ventricular impedance and 2 patients high shock impedance values. All patients were followed-up via remote monitoring and sporadic high impedance values were not associated with adverse outcome or need of revision in all but one patient that presented continuously increasing pacing thresholds due to lead microfracture.
Conclusions
In absence of clear signs of lead fracture or connection issues, sporadic high pacing and shock impedance in hybrid implantable defibrillator systems can be safely managed through close follow-up.

Copyright © 2021. Published by Elsevier Inc.

Heart Rhythm: 06 Apr 2021; epub ahead of print
Pignalberi C, Mariani MV, Castro A, Piro A, ... Fedele F, Lavalle C
Heart Rhythm: 06 Apr 2021; epub ahead of print | PMID: 33838316
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Abstract

Left axis deviation in patients with non-ischemic heart failure and left bundle branch block is a purely electrical phenomenon.

Abu-Alrub S, Strik M, Huntjens P, Ramirez FD, ... Bordachar P, Ploux S
Background
Possible mechanisms of left axis deviation (LAD) in the setting of left bundle branch block (LBBB) include differences in cardiac electrophysiology, structure, or anatomical axis.
Objectives
We sought to clarify the mechanism(s) responsible for LAD in patients with LBBB.
Methods
Twenty-nine patients with non-ischemic cardiomyopathies and LBBB underwent non-invasive electrocardiographic mapping (ECGi), cardiac computed tomography, and magnetic resonance imaging in order to define ventricular electrical activation, characterize cardiac structure, and determine the heart anatomical axis.
Results
Sixteen patients had a normal QRS axis (NA, mean axis: 8±23°) whereas 13 patients had LAD (mean axis: -48±13°, p<0.001). Total activation times were longer in the LAD group (112±25 vs 91±14ms, p=0,01) due to delayed activation of the basal anterolateral region (107±10 vs 81±17ms, p<0.001). Left ventricular (LV) activation in patients with LAD was from apex-to-base, contrasting with a circumferential pattern of activation in patients with NA. The apex-to-base delay was therefore longer in the LA group (95±13 vs 64±21ms, p<0.001) and correlated with the QRS frontal axis (R2=0,67, p<0.001). Both groups were comparable in LV end diastolic volume (295±84vs LAD: 310±91ml; p=0.69), LV mass (177±33 vs LAD: 180±37g, p=0.83) and anatomical axis.
Conclusion
Left axis deviation in left bundle branch block appears to be due to electrophysiological abnormalities rather than structural factors or the cardiac anatomical axis.

Copyright © 2021. Published by Elsevier Inc.

Heart Rhythm: 04 Apr 2021; epub ahead of print
Abu-Alrub S, Strik M, Huntjens P, Ramirez FD, ... Bordachar P, Ploux S
Heart Rhythm: 04 Apr 2021; epub ahead of print | PMID: 33831543
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Abstract

Temperature- and flow-controlled ablation/very-high-power short-duration ablation vs conventional power-controlled ablation: Comparison of focal and linear lesion characteristics.

Takigawa M, Kitamura T, Martin CA, Fuimaono K, ... Haïssaguerre M, Jaïs P
Background
The QDOT MICRO catheter allows temperature- and flow-controlled (TFC) ablation and very-high-power short-duration (vHPSD) ablation.
Objective
The purpose of this study was to compare lesion characteristics between TFC/vHPSD ablation and standard power-controlled (PC) ablation.
Methods
Lesion characteristics in the right atrium, left atrium, and right ventricle (RV) of 6 sheep were compared between vHPSD (90 W/4 seconds, TC mode with 60°C target using QDOT) and standard radiofrequency settings (PC mode, 30 W/30 seconds with ThermoCool SmartTouch SF). Lesions in the left ventricle (LV) were compared, targeting 50 W for 60-second applications.
Results
Forty-six focal atrial lesions, 50 RV focal lesions, and 12 linear lesions were created by vHPSD ablation and PC ablation in each group of 6 animals. vHPSD ablation produced significantly larger focal atrial lesions in length (8.3 [6.4-9.7] mm vs 6.3 [5.2-7.4] mm; P = .0002), width (6.0 [5.3-6.9] mm vs 4.6 [3.8-5.4] mm; P <.0001), and surface area (39.4 [25.4-52.4] mm2 vs 23.6 [16.0-31.1] mm2; P = .0001), with superior transmurality (89.1% vs 69.6%; P = .04) compared to PC ablation. vHPSD ablation produced significantly larger RV lesions in length (7.7 [7.0-8.7] mm vs 6.0 [4.8-6.9] mm; P <.0001), width (6.4 [5.4-7.5] mm vs 4.3 [3.6-5.2] mm; P <.0001), and area (39.4 [29.1-50.1] mm2 vs 19.9 [14.7-25.2] mm2; P <.0001) but similar volume (P = .97) with shallower lesions (2.7 [2.2-3.4] mm vs 3.8 [3.0-4.4] mm; P <.0001). Atrial linear lesions were more homogeneous (P = .02), with fewer gaps in each line (P = .003) with vHPSD ablation. LV focal lesions (15 TFC mode; 21 PC mode) were similar in volume and depth, but lesion size showed less deviation (P <.05) in TFC than PC mode. Fewer steam pops were observed in TFC mode (0% vs 28.6%; P = .03). Hemorrhagic rings around the lesion core were generally smaller with TFC/vHPSD ablation (P <.05).
Conclusion
TFC/vHPSD ablation produces larger, shallower, more homogeneous, and less hemorrhagic lesions. vHPSD Ablation produces more transmural and contiguous linear lesions compared to PC ablation. LV lesions are more homogeneous with fewer steam pops in TFC ablation.

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

Heart Rhythm: 30 Mar 2021; 18:553-561
Takigawa M, Kitamura T, Martin CA, Fuimaono K, ... Haïssaguerre M, Jaïs P
Heart Rhythm: 30 Mar 2021; 18:553-561 | PMID: 33127542
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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 INa and atrial peak INa, 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: 30 Mar 2021; 18:615-622
Opačić D, van Hunnik A, Zeemering S, Dhalla A, ... Schotten U, Verheule S
Heart Rhythm: 30 Mar 2021; 18:615-622 | PMID: 33232809
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Abstract

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

Mehta NK, Doerr K, Skipper A, Rojas-Pena E, Dixon S, Haines DE
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: 30 Mar 2021; 18:641-650
Mehta NK, Doerr K, Skipper A, Rojas-Pena E, Dixon S, Haines DE
Heart Rhythm: 30 Mar 2021; 18:641-650 | PMID: 33242669
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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, BEAT-AF and Swiss-AF Investigators
Background
The occurrence of congestive heart failure (CHF) hospitalization among patients with atrial fibrillation (AF) is a poor prognostic marker.
Objective
The purpose of this study was 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 2 prospective multicenter observational cohort studies that included 3691 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 patient age was 69 ± 12 years, 1028 (28%) were female, and 879 (24%) had a history of CHF. The incidence per 1000 patient-years across increasing IGFBP-7 quartiles was 7, 10, 32, and 85. The corresponding multivariable adjusted hazard ratios (aHRs) (95% confidence interval [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 <.001). In a subgroup of 2812 patients without pre-existing CHF at baseline, the corresponding 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 <.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 1 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 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Heart Rhythm: 30 Mar 2021; 18:512-519
Blum S, Aeschbacher S, Meyre P, Kühne M, ... Conen D, BEAT-AF and Swiss-AF Investigators
Heart Rhythm: 30 Mar 2021; 18:512-519 | PMID: 33278630
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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
The purpose of this study was 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 an anteroseptal substrate.
Methods
Patients with periaortic VT arising from an anteroseptal substrate with preprocedural wideband LGE-CMR were divided into 2 groups by the degree of longitudinal septal LGE extension as full-length septal (≥80% anteroposterior length) or partial septal (<80% anteroposterior length). Septal LGE volumes were quantified in those with and without VT recurrence.
Results
Among 234 patients referred for scar-related VT ablation between 2017 and 2020, 25 patients (92% male; age 64 ± 8 years) 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 (median [interquartile range]: 5 [3-9] vs 2 [1-4]; P = .005). Patients with VT recurrence had larger septal LGE volumes compared to those without recurrence (11.4 mL [8.8-13.9] vs 4.2 mL [0-9.5]; P = .012). At median follow-up of 16 months (5-22), overall freedom from VT recurrence was 52% and significantly higher in patients with partial septal LGE than in those with full-length septal LGE (80% vs 20%; P = .005).
Conclusion
VT originating from an anteroseptal substrate is associated with heterogeneous patterns and extent of CMR septal scar. Preprocedural imaging may substratify this challenging patient population for the propensity for multiple induced VT morphologies and recurrence after catheter ablation.

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

Heart Rhythm: 30 Mar 2021; 18:579-588
Nishimura T, Patel HN, Wang S, Upadhyay GA, ... Patel AR, Tung R
Heart Rhythm: 30 Mar 2021; 18:579-588 | PMID: 33301979
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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
The purpose of this study was 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 atrial isomerism (RAI), left atrial isomerism (LAI), or indeterminate isomerism.
Results
Of the 366 patients enrolled, 326 (89.1%) had RAI, 35 (9.6%) LAI, and 5 (1.4%) indeterminate isomerism; 71 (19.4%) patients were adults. Arrhythmias occurred in 37.2% of patients (109 supraventricular tachycardia [SVT], 8 atrial fibrillation/flutter, 12 ventricular tachycardia, and 14 paced bradycardia). Freedom from arrhythmias by the age of 1, 5, 10, 20, and 40 years was 0.849, 0.680, 0.550, 0.413, and 0.053, respectively. Twin atrioventricular nodes were identified in 51.5% of patients with RAI, 8.7% of patients with LAI, and 40.0% of patients with indeterminate isomerism and were the key predictors of SVT. Indeterminate isomerism was also a risk factor for SVT. 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.
Conclusion
RAI was the predominant subtype of heterotaxy in this cohort. Collectively, the median RAI/LAI 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 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Heart Rhythm: 30 Mar 2021; 18:605-612
Wu MH, Wang JK, Chiu SN, Tseng WC, ... Lin MT, Chen CA
Heart Rhythm: 30 Mar 2021; 18:605-612 | PMID: 33321198
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Abstract

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

Francisco-Pascual J, Rodenas-Alesina E, Rivas-Gándara N, Belahnech Y, ... Maldonado J, Ferreira-González I
Background
Syncope in patients with mid-range left ventricular ejection fraction (LVEF) can be due to potentially serious arrhythmic causes. However, there is no clear consensus on the best way to manage these patients.
Objectives
The objectives of this study were to determine the causes of syncope and assess the diagnostic yield and safety of a stepwise workup protocol in this population.
Methods
This was a prospective observational study. A stepwise workup protocol was applied to patients with LVEF 35%-50% and unexplained syncope after the initial assessment (step 1).
Results
One hundred four patients were included {median age 75.6 years; (interquartile range [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 and electrophysiology study) and 16 (36.5%) in step 3 (implantable cardiac monitor). Arrhythmic causes were the most common etiology (45.2% auriculoventricular block and 9.6% ventricular tachycardia). Sixty patients (57.7%) required the implantation of a cardiac device and 11 had a defibrillation function. Patients diagnosed in step 3 had a higher global risk of recurrence of syncope (hazard ratio 6.5; 95% confidence interval 2.3-18.0). The mortality rate was 8.1 per 100 person-years, and the sudden or unknown death rate was 0.9 per 100 person-years.
Conclusion
In patients with mid-range left ventricular dysfunction and syncope of unknown cause, a systematic diagnostic strategy based on electrophysiology study and/or implantable cardiac monitor 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 auriculoventricular block.

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

Heart Rhythm: 30 Mar 2021; 18:597-604
Francisco-Pascual J, Rodenas-Alesina E, Rivas-Gándara N, Belahnech Y, ... Maldonado J, Ferreira-González I
Heart Rhythm: 30 Mar 2021; 18:597-604 | PMID: 33326869
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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 addressed the importance of anteroseptal scar in patients with nonischemic cardiomyopathy. However, this pattern has never been fully evaluated in patients with prior myocarditis.
Objective
The purpose of this study was to evaluate whether anteroseptal scar is associated with worse outcome in patients with prior myocarditis and how it affects the efficacy of catheter ablation (CA).
Methods
This was a retrospective study of consecutive patients with prior myocarditis and arrhythmic presentation. Cardiac magnetic resonance and electroanatomic voltage mapping were used to identify the scar pattern. Patients were referred for either CA or escalated antiarrhythmic drug (AAD) therapy. The main outcome was ventricular arrhythmia (VA)-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 2-year follow-up, VA-free survival was 77% in the CA group. After CA, the mean number of AADs taken by each patient decreased from 1.8 to 0.9 per day (p<0.001). The presence of anteroseptal scar was found to be an independent predictor of VA relapse both in patients treated with CA (hazard ratio [HR] 3.6; 95% confidence interval [CI] 1.1-11.4; P = .03) and in the overall population (HR 2.0; 95% CI 1.2-3.5; P = .02) .
Conclusion
In patients with prior myocarditis and VA, the presence of anteroseptal scar negatively predicts outcomes irrespective of treatment strategy.

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

Heart Rhythm: 30 Mar 2021; 18:589-596
Casella M, Bergonti M, Narducci ML, Persampieri S, ... Russo AD, Tondo C
Heart Rhythm: 30 Mar 2021; 18:589-596 | 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
Although 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 purpose of this study was to systematically summarize the evidence pertaining to the relationship of PA and risk of AF.
Methods
We searched the PubMed and Embase databases for prospective cohort studies reporting the risk of AF associated with a specific PA volume through 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 (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% female) were included. Individuals achieving guideline-recommended level of PA had a significantly lower risk of AF (hazard ratio 0.94; 95% confidence interval 0.90-0.97; P = .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 © 2021 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Heart Rhythm: 30 Mar 2021; 18:520-528
Mishima RS, Verdicchio CV, Noubiap JJ, Ariyaratnam JP, ... Sanders P, Elliott AD
Heart Rhythm: 30 Mar 2021; 18:520-528 | PMID: 33348059
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Impact:
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 arrhythmia occurring in humans, and new treatment strategies are critically needed. The lack of reliable preclinical animal models of AF is a major limitation to drug development of novel antiarrhythmic compounds.
Objective
The purpose of this study was to provide a comprehensive head-to-head assessment of 5 canine AF models.
Methods
Five canine models were evaluated for the efficacy of AF induction and AF duration. We tested 2 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. 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 treatment.

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

Heart Rhythm: 30 Mar 2021; 18:632-640
Freudenberger T, Kranz B, Lehmann W, Schäfer K, ... Ellinor PT, Hucker WJ
Heart Rhythm: 30 Mar 2021; 18:632-640 | PMID: 33346136
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Impact:
Abstract

Catheter ablation of ventricular arrhythmias in left ventricular noncompaction cardiomyopathy.

Sánchez Muñoz JJ, Muñoz-Esparza C, Verdú PP, Sánchez JM, ... Gimeno Blanes JR, Alberola AG
Background
There are limited data on ventricular arrhythmias (VAs) associated with left ventricular noncompaction (LVNC) cardiomyopathy.
Objectives
This study aims to analyze the clinical and electrocardiographic characteristics of VAs in a group of patients with LVNC.
Methods
Forty-two nonrelated patients with LVNC and VAs were included that were evaluated at the Inherited Cardiac Disease Unit of the University Hospital Virgen Arrixaca (Murcia-Spain) (ERN Guard-Heart Centre, European Reference Network for Rare and Low Prevalence Complex Diseases of the Heart).
Results
Thirteen patients (30.9%) had isolated LVNC, 27 (64.3%) had LVNC associated with dilated cardiomyopathy, and 2 (4.8%) had LVNC associated with hypertrophic cardiomyopathy. Among isolated LVNC individuals, 9 (69.2%) had premature ventricular complexes (PVCs)/nonsustained ventricular tachycardias (VTs), and 4 (30.8%) VTs (1 VT degenerating in ventricular fibrillation). In the dilated cardiomyopathy group, 11 (40.7%) patients had PVCs, 14 (51.9%) VTs, and 2 (7.4%) ventricular fibrillation. In the hypertrophic cardiomyopathy group, one patient had PVCs and the other VTs. Endocardial mapping and ablation were performed in 19 patients (45.2%): 7 ventricular outflow tracts (4 right ventricular outflow tract, 1 left coronary cusp, and 2 right coronary cusp), 2 in the left ventricular summit, 5 related to Purkinje potentials at the mid inferoseptal area, and 5 associated with endocardial scar localized in the basal anterolateral and inferolateral segments. Epicardial ablation was performed in 3 cases.
Conclusion
The substrate of VAs in LVNC cardiomyopathy is heterogeneous, with origin in ventricular outflow tracts, Purkinje system related, and resembling scar patterns in nonischemic cardiomyopathy.

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

Heart Rhythm: 30 Mar 2021; 18:545-552
Sánchez Muñoz JJ, Muñoz-Esparza C, Verdú PP, Sánchez JM, ... Gimeno Blanes JR, Alberola AG
Heart Rhythm: 30 Mar 2021; 18:545-552 | PMID: 33346135
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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 placing the pacing lead deep enough in the septum to reach the LBB area, yet not too deep to avoid perforation.
Objective
The purpose of this study was to investigate whether the occurrence of the ectopic beats with qR/rsR\' morphology in lead V1 (fixation beats) during lead fixation would predict whether the desired intraseptal lead depth had been reached, whereas the lack of fixation beats would indicate a too-shallow position and the 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 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 vs during the events before intermediate/unsuccessful positions.
Results
A total of 339 patients and 1278 lead rotation events were analyzed. In the retrospective phase, fixation beats were observed in 327 of 339 final lead positions and in 9 of 939 intermediate lead positions (P <.001). Sensitivity, specificity, and positive and negative predictive values 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, 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 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Heart Rhythm: 30 Mar 2021; 18:562-569
Jastrzębski M, Kiełbasa G, Moskal P, Bednarek A, ... Rajzer M, Vijayaraman P
Heart Rhythm: 30 Mar 2021; 18:562-569 | PMID: 33359876
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Impact:
Abstract

Systematic quantification of histologic 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
The purpose of this study was 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 noncardiac 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-to-epicardial distribution of fibrosis within the left ventricle was specifically characterized.
Results
Seventeen cases with iMVP-SCD were matched 1:1 with 17 controls, yielding 149 samples and 1788 histologic regions. The iMVP-SCD group had increased left ventricular (anterior, lateral, and posterior; all P <.001) and interventricular septum fibrosis (P <.001), but similar amounts of right ventricular fibrosis (P = .62) compared to controls. In iMVP-SCD, left ventricular fibrosis was significantly higher in the lateral and posterior walls compared to the anterior wall and interventricular septum (all P <.001). Within the lateral and posterior walls, iMVP-SCD cases had a significant endocardial-to-epicardial gradient of cardiac fibrosis (P <.01) similar to other known conditions that cause cardiac remodeling.
Conclusion
Our study indicates that nonuniform left ventricular remodeling with both localized and generalized left ventricular fibrosis is important in the pathogenesis of SCD in individuals with MVP.

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

Heart Rhythm: 30 Mar 2021; 18:570-576
Han HC, Parsons SA, Curl CL, Teh AW, ... Delbridge LMD, Lim HS
Heart Rhythm: 30 Mar 2021; 18:570-576 | PMID: 33359875
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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 2-dimensional speckle tracking is frequently observed in patients with atrial fibrillation (AF) and associated with the risk of ischemic stroke.
Objectives
We aimed to study the predictive power of the decrease in LA strain in population with AF 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 [GE Vivid i system (GE Healthcare, Horten, Norway)]. The standard score of LA strain (ZLA) was calculated, and patients were classified into 5 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
Of the 1364 subjects with AF (mean age 71.4 ± 12.1 years; 759 men (55.6%), 105 encountered ischemic strokes during a mean follow-up period 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 3.697; 95% confidence interval 1.966-6.951; P < .001) and Z-4 (hazard ratio 6.447; 95% confidence interval 2.990-13.904; P < .001) groups in univariate Cox regression analysis. The results remained consistent after multivariate Cox regression analysis.
Conclusion
The decrease in LA strain could be applied in a stratified manner and is significantly associated with the risk of stroke independent of the baseline covariates.

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

Heart Rhythm: 30 Mar 2021; 18:538-544
Liao JN, Chao TF, Hung CL, Chen SA
Heart Rhythm: 30 Mar 2021; 18:538-544 | 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 ablation of epicardial and mid-myocardial ventricular arrhythmias is limited by lesion depth.
Objective
The purpose of this study was to generate deep mid-interventricular septal (IVS) lesions using high-intensity ultrasound (US) from an endocardial catheter-based approach.
Methods
Irrigated US catheters (12 F) were fabricated with 3 × 5 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 magnetic resonance imaging, 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 mm; 95% confidence interval [CI] 9.9-12.4 mm) and at 30 days (11.2 mm; 95% CI 10.6-12.4 mm) (P = .56). Lesion volume decreased post-ablation to 30 days (from 255 [95% CI 198-440] to 162 [95% CI 133-234] mm3; P = .05), yet transmurality increased from 58% (95% CI 50%-76%) to 81% (95% CI 74%-93%), attributable to a reduction in IVS thickness (from 16.0 ± 1.7 to 10.6 ± 2.4 mm; P = .007). Magnetic resonance imaging 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.
Conclusion
High-intensity US catheter ablation may be an effective treatment of mid-myocardial or epicardial ventricular arrhythmias from an endocardial approach.

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

Heart Rhythm: 30 Mar 2021; 18:623-631
Nazer B, Giraud D, Zhao Y, Hodovan J, ... Gerstenfeld EP, Lindner JR
Heart Rhythm: 30 Mar 2021; 18:623-631 | PMID: 33385570
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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.
Objective
The purpose of this study was to examine a novel comprehensive ablation strategy (Marshall bundle elimination, Pulmonary vein isolation, and Line completion for ANatomical ablation of persistent atrial fibrillation [Marshall-PLAN]) strictly based on anatomical considerations.
Methods
Left atrial (LA) sites were sequentially targeted as follows: (1) 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 women; 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 patients (91%). At 12 months, 54 of 75 patients (72%) 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 of 75 patients (89%) remained free from AF/AT (no antiarrhythmic drugs). After 1 or 2 procedures, VOM ethanol infusion was complete in 72 of 75 patients (96%).
Conclusion
A novel ablation strategy that systematically targets anatomical 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 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Heart Rhythm: 30 Mar 2021; 18:529-537
Derval N, Duchateau J, Denis A, Ramirez FD, ... Jaïs P, Pambrun T
Heart Rhythm: 30 Mar 2021; 18:529-537 | PMID: 33383226
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Impact:
Abstract

Persistent Atrial Fibrillation Ablation in Cardiac Laminopathy: Electrophysiological Findings and Clinical Outcomes.

Chauvel R, Derval N, Duchateau J, Denis A, ... Haïssaguerre M, Pambrun T
Background
Little is known about persistent atrial fibrillation (AF) ablation in patients with cardiac laminopathy (CLMNA).
Objective
We aimed to characterize atrial electrophysiological properties and to assess the long-term outcomes of persistent AF ablation in CLMNA patients.
Methods
All CLMNA patients referred in our center for persistent AF ablation were retrospectively included. Left atrium (LA) volume, left atrial appendage (LAA) cycle length (CL), inter-atrial conduction delay and LA voltage amplitude were analyzed during the ablation procedure. Sinus rhythm maintenance and LA contractile function were assessed during long-term follow-up.
Results
From 2011 to 2020, 8 patients were included (47 ± 14 years; 3 women). LA volume was 205.8 ± 43.7mL, LAA AF CL was 250.7 ± 85.6ms and inter-atrial conduction delay was 296.5 ± 110.1ms. Large low voltage areas (>50% of LA surface; < 0,5mV EGM) were recorded in all 8 patients. 2 patients had inadvertent LAA disconnection during ablation. All A wave recorded by pulsed doppler in sinus rhythm were < 30cm/s, before, and after AF ablation. Early arrhythmia recurrence was recorded in 7 (87%) patients (time to recurrence 4 ± 4 months; 1.5 procedures per patient). After a mean follow-up of 4.4 ± 3.2 years, 4 patients underwent ICD therapy for life threatening ventricular arrhythmia and 3 patients finally underwent heart transplantation (HT).
Conclusion
Persistent AF patients afflicted by CLMNA exhibit severe LA impairment due to large low-voltage areas, prolonged conduction velocity and reduced contractile function. Ablation procedures have a limited impact with a high recurrence rate.

Copyright © 2021. Published by Elsevier Inc.

Heart Rhythm: 30 Mar 2021; epub ahead of print
Chauvel R, Derval N, Duchateau J, Denis A, ... Haïssaguerre M, Pambrun T
Heart Rhythm: 30 Mar 2021; epub ahead of print | PMID: 33812085
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Impact:
Abstract

Differentiating atrial tachycardias with centrifugal activation: Lessons from high-resolution mapping.

Takigawa M, Takagi T, Martin CA, Derval N, ... Sasano T, Jais P
Background
A centrifugal activation is not always the origin of a focal-AT (True-Focal), but a passive activation from the other structures (Pseudo-Focal).
Objective
We aimed to establish a method to differentiate \'True-focal\' from \'Pseudo-Focal\'.
Methods
In 49 centrifugal activations in 35 AT-patients, 12-lead ECG, activation map, atrial global activation histogram (GAH), and local electrograms were analyzed. GAH demonstrates the relation between the activation area and timing through the cycle-length, displayed with a normalized-value, ranging from 0 (smallest activation-area) to 1.0 (largest activation-area).
Results
Of 30 centrifugal activations observed in the septal region, 6 were \'True-Focal\'. The remaining 24 were \'Pseudo-Focal\', of which 23/24 (95.8%) were from the opposite chamber. P-wave/flutter-waves duration<200ms discriminated the \'True-Focal\' from the \'Pseudo-Focal\' (sensitivity=100%, specificity=54.5%, positive predictive value (PPV)=33.3%, and negative predictive value (NPV)=100%). Multiple-breakthrough ruled out the possibility of a \'True-Focal\' AT. Other differentiating factors were an activation area within initial 20ms <5mm2 and a typical QS pattern-electrograms at the origin. Of 19 centrifugal activations observed outside septal regions, 7 were \'True-Focal\' and 12 were \'Pseudo-Focal\' exited from an epicardial structure: 10/12 (83.3%) were located around the LAA and ridge. Flutter-wave, GAH<0.05, and GAH<0.1 for more than 110ms of cycle-length differentiated a \'True\' from a \'Pseudo-Focal\' with sensitivity/NPV of 100%. GAH<0.1 for more than 40% of cycle-length simply discriminated a \'True\' from a \'Pseudo\' with 100% accuracy.
Conclusion
Centrifugal activation is not necessarily due to a focal AT but a passive activation. The activation map with the GAH in addition to 12-lead ECG and local-EGMs enables an accurate differentiation.

Copyright © 2021. Published by Elsevier Inc.

Heart Rhythm: 28 Mar 2021; epub ahead of print
Takigawa M, Takagi T, Martin CA, Derval N, ... Sasano T, Jais P
Heart Rhythm: 28 Mar 2021; epub ahead of print | PMID: 33794392
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Impact:
Abstract

Transvenous lead extraction in 1000 patients guided by intraprocedural risk stratification without surgical backup.

Issa ZF
Background
Transvenous lead extraction (TLE) carries a significant risk of morbidity and mortality. Reliable preprocedural risk predictors to guide resource allocation and optimize procedural safety are lacking.
Objective
The aim of this study was to evaluate an intraprocedural approach to risk stratification during elective TLE procedures.
Methods
This is a single-center retrospective study of consecutive patients who underwent elective TLE of a pacemaker or implantable cardioverter-defibrillator lead for noninfectious indications. The risk of TLE is judged intraprocedurally only after an attempt is made to extract the target lead as long as high-risk extraction techniques are avoided. TLE was performed in a well-equipped electrophysiology laboratory with rescue strategies in place but in the absence of surgical staff.
Results
During the study period, 1000 patients were included in this analysis (52.7% female; mean age 61.5 ± 10.2 years). TLE was attempted for 1362 leads, with a mean lead dwell time of 73 ± 43 months (median 70 months; interquartile range 12-180 months). TLE was successful in 914 patients, partially successful in 10, and failed in 76 patients. A laser sheath was required for extraction of 926 leads (68%). Only 1 patient developed intraprocedural cardiac tamponade requiring emergency pericardiocentesis. None of the patients developed hemothorax or required surgical intervention.
Conclusion
At experienced centers, intraprocedural risk stratification for TLE that avoids high-risk extraction techniques achieved successful TLE in the majority of patients and can potentially help optimize the balance between efficacy, safety, and efficiency in lead extraction.

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

Heart Rhythm: 26 Mar 2021; epub ahead of print
Issa ZF
Heart Rhythm: 26 Mar 2021; epub ahead of print | PMID: 33781982
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Impact:
Abstract

Relationship of paced left bundle branch pacing morphology with anatomic location and physiological outcomes.

Lin J, Hu Q, Chen K, Dai Y, ... Gold MR, Zhang S
Background
Left bundle branch pacing (LBBP) is an emerging physiological pacing modality. However, little is known about pacing at different locations on the left bundle branch (LBB).
Objective
The purpose of this study was to explore pacing and physiological characteristics associated with different LBBP locations.
Methods
The study included 68 consecutive patients with normal unpaced QRS duration and successful LBBP implantation. Patients were divided into 3 groups according to the paced QRS complex as left bundle branch trunk pacing (LBTP), left posterior fascicular pacing (LPFP), or left anterior fascicular pacing (LAFP). Electrocardiographic (ECG) characteristics, pacing parameters, and fluoroscopic localization were collected and analyzed.
Results
There were 17 (25.0%), 35 (51.5%), and 16 (23.5%) patients in the LBTP, LPFP, and LAFP groups, respectively. All subgroups had relatively narrow paced QRS complex (128.6 ± 9.1 ms vs 133.7 ± 11.2 ms vs 134.8 ± 9.6 ms; P = .170), fast left ventricular activation (70.4 ± 9.0 ms vs 70.6 ± 10.2 ms vs 71.0 ± 9.0 ms; P = .986), as well as low and stable pacing thresholds. Delayed right ventricular activation and interventricular dyssynchrony were similar between groups. Fluoroscopic imaging indicated that the lead tip was located most commonly in the basal-middle region of the septum (67.7%), and this was independent of paced QRS morphology group (88.2% vs 57.1% vs 68.8%; P = .106).
Conclusion
Pacing at different sites of the LBB resulted in similar intraventricular and interventricular electrical synchrony in patients with an intact conduction system. Fluoroscopic imaging alone could not predict specific LBBP paced ECG morphology.

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

Heart Rhythm: 26 Mar 2021; epub ahead of print
Lin J, Hu Q, Chen K, Dai Y, ... Gold MR, Zhang S
Heart Rhythm: 26 Mar 2021; epub ahead of print | PMID: 33781981
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Impact:
Abstract

Low-temperature electrocautery reduces adverse effects from secondary cardiac implantable electronic device procedures: Insights from the WRAP-IT trial.

Mittal S, Wilkoff BL, Poole JE, Kennergren C, ... Holbrook R, Tarakji KG
Background
Cardiac device procedures require tissue dissection to free existing device lead(s). Common techniques include blunt dissection, standard electrocautery, and low-temperature electrocautery (PlasmaBlade, Medtronic); however, data on the type of electrosurgical tool used and the development of procedure- or lead-related adverse events are limited.
Objective
The purpose of this study was to determine whether standard or low-temperature electrocautery impacts the development of an adverse event.
Methods
We evaluated patients enrolled in WRAP-IT (Worldwide Randomized Antibiotic EnveloPe Infection PrevenTion Trial) undergoing cardiac implantable electronic device (CIED) revision, upgrade, or replacement. All adverse events were adjudicated by an independent physician committee. Data were analyzed using Cox proportional hazard regression modeling.
Results
In total, 5641 patients underwent device revision/upgrade/replacement. Electrocautery was used in 5205 patients (92.3%) (mean age 70.6 ± 12.7 years; 28.8% female), and low-temperature electrocautery was used in 1866 patients (35.9%). Compared to standard electrocautery, low-temperature electrocautery was associated with a 23% reduction in the incidence of a procedure- or lead-related adverse event through 3 years of follow up (hazard ratio [HR] 0.77; 95% confidence interval [CI] 0.65-0.91; P = .002). After controlling for the number of active leads, degree of capsulectomy, degree of lead dissection, and renal dysfunction, low-temperature electrocautery was associated with a 32% lower risk of lead-related adverse events (HR 0.68; 95% CI 0.52-0.89; P = .004). These effects were consistent across a spectrum of lead-related adverse event types.
Conclusion
This study represents one of the largest assessments of electrocautery use in patients undergoing CIED revision, upgrade, or replacement procedures. Compared to standard electrocautery, low-temperature electrocautery significantly reduces adverse effects from these procedures.

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

Heart Rhythm: 26 Mar 2021; epub ahead of print
Mittal S, Wilkoff BL, Poole JE, Kennergren C, ... Holbrook R, Tarakji KG
Heart Rhythm: 26 Mar 2021; epub ahead of print | PMID: 33781980
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Impact:
Abstract

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

van den Heuvel LM, Do J, Yeates L, MacLeod H, ... van Tintelen JP, Ingles J
Background
Thorough investigation of sudden cardiac death (SCD) in those aged 1-40 years commonly reveals a heritable cause, yet access to postmortem genetic testing is variable.
Objective
We aimed to explore practices of postmortem genetic testing and attitudes of healthcare professionals worldwide.
Methods
A survey was administered among healthcare professionals recruited through professional associations, social media and networks of researchers. Topics included practices around postmortem genetic testing, level of confidence in healthcare professionals\' ability, and attitudes towards postmortem genetic testing practices.
Results
There were 112 respondents, with 93% from North America, Europe and Australia/New Zealand, and 7% from South America, Asia and Africa. Only 30% reported autopsy as mandatory, and overall practices were largely case-by-case and not standardised. North American respondents (87%) more often perceived practices as ineffective compared to those from Europe (58%) and Australia/New Zealand (48%, p=0.002). Where a heritable cause is suspected, 69% considered postmortem genetic testing and 61% offered genetic counseling to surviving family members; financial resources varied widely. Half believed practices in their countries perpetuated health inequalities.
Conclusion
Postmortem genetic testing is not consistently available in the investigation of young SCD despite being a recommendation in international guidelines. Access to postmortem genetic testing, which is critical in ascertaining a cause of death in many cases, must be guided by well-resourced multidisciplinary teams.

Copyright © 2021. Published by Elsevier Inc.

Heart Rhythm: 25 Mar 2021; epub ahead of print
van den Heuvel LM, Do J, Yeates L, MacLeod H, ... van Tintelen JP, Ingles J
Heart Rhythm: 25 Mar 2021; epub ahead of print | PMID: 33781984
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Impact:
Abstract

Vein of Marshall ethanol infusion in the treatment of atrial fibrillation: From concept to clinical practice.

Valderrábano M
The vein of Marshall (VOM) contains innervation, myocardial connections, and arrhythmogenic foci that make it an attractive target in catheter ablation of atrial fibrillation (AF). Additionally, it co-localizes with the mitral isthmus, which is critical to sustain perimitral flutter, and is a true atrial vein that communicates with underlying myocardium. Retrograde balloon cannulation of the VOM from the coronary sinus is feasible and allows for ethanol delivery, which results in rapid ablation of neighboring myocardium and its innervation. Here we review the body of work performed over a span of 13 years, from the inception of the technique, to its preclinical validation, to demonstration of its ablative and denervation effects, and finally to completion of a randomized clinical trial demonstrating favorable outcomes, improving rhythm control in catheter ablation of persistent AF.

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

Heart Rhythm: 25 Mar 2021; epub ahead of print
Valderrábano M
Heart Rhythm: 25 Mar 2021; epub ahead of print | PMID: 33781979
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Impact:
Abstract

Defining idiopathic ventricular fibrillation: A systematic review of diagnostic testing yield in apparently unexplained cardiac arrest.

Alqarawi W, Dewidar O, Tadros R, Roberts JD, ... Wells G, Krahn AD
Background
Idiopathic ventricular fibrillation (IVF) is diagnosed in patients with apparently unexplained cardiac arrest (UCA) after varying degrees of evaluation. This is largely due to the lack of a standardized approach to UCA.
Objective
We sought to develop an evidence-based diagnostic algorithm for IVF by systematically examining the yield of diagnostic testing in UCA probands.
Methods
Studies reporting the yield of diagnostic testing in UCA were identified in MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and conference abstracts. Their methodological quality was assessed by the National Institutes of Health quality assessment tool. Meta-analyses were performed using the random effects model.
Results
A total of 21 studies were included. The pooled comprehensive diagnostic testing yield was 43% (95% confidence interval 39%-48%). A lower yield was seen when only definite diagnoses based on the prespecified criteria were used (32% vs 47%; P = .15). Epinephrine challenge, Holter monitoring, and family screening were associated with low yield (<5%), whereas cardiac magnetic resonance imaging, exercise treadmill test, and sodium-channel blocker challenge were associated with high yield (≥5%). Coronary spasm provocation, electrophysiology study, and systematic genetic testing were reported to be abnormal in a high proportion of UCA probands (>10%).
Conclusion
We developed a stepwise algorithm for UCA evaluation and criteria to assess the strength of IVF diagnosis on the basis of the diagnostic yield of UCA testing.

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

Heart Rhythm: 25 Mar 2021; epub ahead of print
Alqarawi W, Dewidar O, Tadros R, Roberts JD, ... Wells G, Krahn AD
Heart Rhythm: 25 Mar 2021; epub ahead of print | PMID: 33781978
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Impact:
Abstract

Association of SGLT2 Inhibitors with Arrhythmias and Sudden Cardiac Death in Patients with Type 2 Diabetes or Heart Failure: A Meta-Analysis of 34 Randomized Controlled Trials.

Fernandes GC, Fernandes A, Cardoso R, Penalver J, ... Myerburg RJ, Goldberger JJ
Background
Sodium-glucose cotransporter 2 inhibitors (SGLT2i) reduce hospitalizations and death from heart failure (HF), but their effect on arrhythmia expression has been poorly investigated.
Objective
To evaluate the association of SGLT2i with arrhythmias in patients with type 2 diabetes mellitus (T2DM) or HF.
Methods
We searched Pubmed and ClinicalTrials.gov. Two independent investigators identified randomized, double-blind trials that compared SGLT2i with placebo or active control for adults with T2DM or HF. Primary outcomes were incident atrial arrhythmias, ventricular arrhythmias (VA) and sudden cardiac death (SCD).
Results
We included 34 randomized (25 placebo-controlled and 9 active-controlled) trials with 63,166 patients (35,883 SGLT2i vs 27,273 control - mean age 53-67 years, 63% male). Medications included canagliflozin, dapagliflozin, empagliflozin or ertugliflozin. Except for one study on HF, all patients had T2DM. Follow-up ranged from 24 weeks to 5.7 years. The cumulative incidence of events was low - 3.6, 1.4 and 2.5 per 1,000 patient-years for atrial arrhythmias, VA and SCD, respectively. SGLT2i therapy was associated with a significant reduction in risk of incident atrial arrhythmias (OR, 0.81, 95% CI 0.69-0.95; P=0.008) and the \"SCD\" component of the SCD outcome (OR, 0.72, 95% CI 0.54-0.97; P=0.03) compared with control. There was no significant difference in incident VA or the \"cardiac arrest\" SCD component between groups.
Conclusions
SGLT2i are associated with significantly reduced risks of incident atrial arrhythmias and SCD in patients with T2DM. Prospective trials are warranted to confirm the antiarrhythmic effect of SGLT2i and whether this is a class or drug-specific effect.

Copyright © 2021. Published by Elsevier Inc.

Heart Rhythm: 19 Mar 2021; epub ahead of print
Fernandes GC, Fernandes A, Cardoso R, Penalver J, ... Myerburg RJ, Goldberger JJ
Heart Rhythm: 19 Mar 2021; epub ahead of print | PMID: 33757845
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Impact:
Abstract

Effect of preload reducing therapy on right ventricular size and function in patients with arrhythmogenic right ventricular cardiomyopathy.

Kalantarian S, Vittinghoff E, Klein L, Scheinman MM
Background
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an important cause of sudden cardiac death in young people and athletes. To date, no treatment has proven to slow the progression of the disease. Preload reducing agents such as nitrates and diuretics have shown promising results in preventing training-induced development of ARVC in a murine model.
Objective
The purpose of this study was to describe our experience with preload reducing therapy in patients with ARVC and symptomatic right ventricular (RV) dysfunction.
Methods
We performed retrospective chart review of prospectively collected registry data and included 20 patients with definite ARVC who had serial echocardiographic measurements and an implantable cardioverter-defibrillator. Six of the 20 patients with RV end-diastolic area (RVEDA) above median (>25 cm2) and New York Heart Association functional class II-IV symptoms were successfully treated with long-term isosorbide dinitrate 5-40 mg tid (at maximum tolerated dose) and hydrochlorothiazide-spironolactone 25-25 mg daily. The main outcomes of interest were RVEDA, RV fractional area change (FAC), and RV outflow tract measurements. Generalized estimating equations with repeated measures were used to identify the association between preload reducing agents and echocardiographic structural progression.
Results
Patients who received preload reducing agents (n = 6) were older and had larger RVs with lower FAC at baseline. However, treatment with preload reducing agents was associated with less RVEDA enlargement during mean 3.3 (range 1-6.7) years of treatment in multivariate analysis (% change in RVEDA associated with treatment -7.71; 95% confidence interval -13.29 to -2.13; P = .007).
Conclusion
Preload reducing agents show promising results in slowing RV enlargement in patients with ARVC and show possible disease-modifying potential.

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

Heart Rhythm: 16 Mar 2021; epub ahead of print
Kalantarian S, Vittinghoff E, Klein L, Scheinman MM
Heart Rhythm: 16 Mar 2021; epub ahead of print | PMID: 33722762
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Impact:
Abstract

Atrial resting membrane potential confers sodium current sensitivity to propafenone, flecainide, and dronedarone.

Holmes AP, Saxena P, Kabir SN, O\'Shea C, ... Fabritz L, Kirchhof P
Background
Although atrial fibrillation ablation is increasingly used for rhythm control therapy, antiarrhythmic drugs (AADs) are commonly used, either alone or in combination with ablation. The effectiveness of AADs is highly variable. Previous work from our group suggests that alterations in atrial resting membrane potential (RMP) induced by low Pitx2 expression could explain the variable effect of flecainide.
Objective
The purpose of this study was to assess whether alterations in atrial/cardiac RMP modify the effectiveness of multiple clinically used AADs.
Methods
The sodium channel blocking effects of propafenone (300 nM, 1 μM), flecainide (1 μM), and dronedarone (5 μM, 10 μM) were measured in human stem cell-derived cardiac myocytes, HEK293 expressing human NaV1.5, primary murine atrial cardiac myocytes, and murine hearts with reduced Pitx2c.
Results
A more positive atrial RMP delayed INa recovery, slowed channel inactivation, and decreased peak action potential (AP) upstroke velocity. All 3 AADs displayed enhanced sodium channel block at more positive atrial RMPs. Dronedarone was the most sensitive to changes in atrial RMP. Dronedarone caused greater reductions in AP amplitude and peak AP upstroke velocity at more positive RMPs. Dronedarone evoked greater prolongation of the atrial effective refractory period and postrepolarization refractoriness in murine Langendorff-perfused Pitx2c+/- hearts, which have a more positive RMP compared to wild type.
Conclusion
Atrial RMP modifies the effectiveness of several clinically used AADs. Dronedarone is more sensitive to changes in atrial RMP than flecainide or propafenone. Identifying and modifying atrial RMP may offer a novel approach to enhancing the effectiveness of AADs or personalizing AAD selection.

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

Heart Rhythm: 15 Mar 2021; epub ahead of print
Holmes AP, Saxena P, Kabir SN, O'Shea C, ... Fabritz L, Kirchhof P
Heart Rhythm: 15 Mar 2021; epub ahead of print | PMID: 33737232
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Impact:
Abstract

Fasciculoventricular and atrioventricular accessory pathways in patients with Danon disease and preexcitation: A multicenter experience.

Darden D, Hsu JC, Tzou W, von Alvensleben JC, ... Feld GK, Adler E
Background
Studies have suggested that a fasciculoventricular pathway (FVP) may be the cause of preexcitation in patients with Danon disease, a rare X-linked dominant genetic disorder of hypertrophic cardiomyopathy.
Objective
The purpose of this study was to describe the prevalence of ventricular preexcitation on resting 12-lead electrocardiogram (ECG) in patients with Danon disease and the electrophysiological study (EPS) results of those with preexcitation.
Methods
Patients with confirmed Danon disease diagnosed with preexcitation (PR ≤120 ms, delta wave, QRS >110 ms) on ECG were included from a multicenter registry. The incidence of arrhythmias, implantable cardioverter-defibrillator (ICD) procedures, ICD shocks, and EPS results were collected.
Results
Thirteen of 40 patients (32.5%) with Danon disease were found to have preexcitation (mean age 17.3 years; 38% women). EPS performed in 9 of 13 patients (69%) demonstrated FVP only in 2 (22.2%), extranodal pathway without exclusion of FVP in 2 (22.2%), and both FVP and extranodal pathway in 5 (55.6%). Two patients had malignant accessory pathway (AP) properties. Over median follow-up of 842 days (interquartile range 138-1678), 11 patients (85%) had ICD placement, and 6 (46.1%) underwent heart transplantation. No patients required therapy for ventricular tachycardia, and 2 patients (15%) had paroxysmal atrial fibrillation.
Conclusion
In a large multicenter cohort of patients with Danon disease, there was a high prevalence of FVP and extranodal pathways diagnosed on EPS in those with preexcitation. These findings suggest patients with preexcitation and Danon disease should undergo EPS to assess for FVP and potentially malignant extranodal AP.

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

Heart Rhythm: 15 Mar 2021; epub ahead of print
Darden D, Hsu JC, Tzou W, von Alvensleben JC, ... Feld GK, Adler E
Heart Rhythm: 15 Mar 2021; epub ahead of print | PMID: 33737230
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Impact:
Abstract

Significance of manifest localized staining during ethanol infusion into the vein of Marshall.

Takagi T, Pambrun T, Nakashima T, Vlachos K, ... Jaïs P, Derval N
Background
Localized staining due to venule injury is attributable to ethanol infusion into the vein of Marshall (Et-VOM).
Objective
The purpose of this study was to investigate adverse outcomes of localized staining during Et-VOM in patients undergoing ablation for atrial fibrillation.
Methods
Two hundred four patients (age 64 ± 10 years; 153 male) were sorted based on the aspect of localized staining. Staining of atrial myocardium that spread uniformly along the VOM vascular tree following selective VOM venography was considered normal, in contrast to predominantly localized staining that spread concentrically from a focal point due to vascular injury. Outcomes between the 2 groups were compared.
Results
Localized staining was observed in 27% of patients. No patients developed clinically significant pericardial effusions during Et-VOM; however, 7 patients developed pericardial effusions on the first postprocedural day (3.6% in patients with vs 3.4% in patients without localized staining). No significant difference was found in achievement of acute mitral isthmus (MI) block (96% vs 98%) and size of the endocardial low-voltage area (8.5 ± 4.1 cm2 vs 9.3 ± 5.3 cm2) in patients with and without localized staining, respectively. Long-term follow-up was not impacted by localized staining. Freedom from recurrent atrial tachyarrhythmias (66% vs 76%) and durability of MI block (57% vs 54%) were not significantly different with and without localized staining. There were no cases of rehospitalization for pericarditis, chronic pericardial effusion, or heart failure.
Conclusion
In our study, localized staining was frequent but was not associated with clinically relevant impact or disadvantages.

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

Heart Rhythm: 15 Mar 2021; epub ahead of print
Takagi T, Pambrun T, Nakashima T, Vlachos K, ... Jaïs P, Derval N
Heart Rhythm: 15 Mar 2021; epub ahead of print | PMID: 33741483
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Impact:
Abstract

Arrhythmogenic mechanisms of acute obstructive respiratory events in a porcine model of drug-induced long QT.

Linz B, Sattler SM, Flethoj M, Høtbjerg Hansen ME, ... Tfelt-Hansen J, Jespersen T
Background
Obstructive sleep apnea is associated with increased risk of sudden cardiac death.
Objective
The purpose of this study was to elucidate changes in ventricular repolarization and electromechanical interaction during obstructive respiratory events simulated by intermittent negative upper airway pressure (INAP) in pigs. We also investigated the effect of a reduced repolarization reserve in drug-induced long QT (LQT) following INAP-induced changes in ventricular repolarization.
Methods
In sedated spontaneously breathing pigs, 75 seconds of INAP was applied by a negative pressure device connected to the endotracheal tube. Ventricular electromechanical coupling was determined by the electromechanical window (EMW) before (pre-INAP), during (INAP), and after INAP (post-INAP). Incidence rates of premature ventricular contractions (PVCs) were measured respectively. A drug-induced LQT was modeled by treating the pigs with the hERG1 blocker dofetilide (DOF).
Results
Whereas QT interval increased during and decreased after INAP (pre-INAP: 273 ± 5 ms; INAP 281 ± 6 ms; post-INAP 254 ± 9 ms), EMW shortened progressively throughout INAP and post-INAP periods (pre-INAP 81 ± 4 ms; post-INAP 44 ± 7 ms). DOF shortened EMW at baseline. Throughout INAP, EMW decreased in a comparable fashion as before DOF (pre-INAP/+DOF 61 ± 7 ms; post-INAP/+DOF 14 ± 9 ms) but resulted in shorter absolute EMW levels. Short EMW levels were associated with increased occurrence of PVCs (pre-INAP 7 ± 2 ms vs post-INAP 26 ± 6 ms; P = .02), which were potentiated in DOF pigs (pre-INAP/+DOF 5 ± 2 ms vs post-INAP/+DOF 40 ± 8 ms; P = .006). Administration of atenolol prevented post-INAP EMW shortening and decreased occurrence of PVCs.
Conclusion
Transient dissociation of ventricular electromechanical coupling during simulated obstructive respiratory events creates a dynamic ventricular arrhythmogenic substrate, which is sympathetically mediated and aggravated by drug-induced LQT.

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

Heart Rhythm: 14 Mar 2021; epub ahead of print
Linz B, Sattler SM, Flethoj M, Høtbjerg Hansen ME, ... Tfelt-Hansen J, Jespersen T
Heart Rhythm: 14 Mar 2021; epub ahead of print | PMID: 33722764
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Impact:
Abstract

Effect of ivabradine on cardiac arrhythmias: Antiarrhythmic or proarrhythmic?

Marciszek M, Paterek A, Oknińska M, Zambrowska Z, Mackiewicz U, Mączewski M
Cardiac arrhythmias are a major source of mortality and morbidity. Unfortunately, their treatment remains suboptimal. Major classes of antiarrhythmic drugs pose a significant risk of proarrhythmia, and their side effects often outweigh their benefits. Therefore, implantable devices remain the only truly effective antiarrhythmic therapy, and new strategies of antiarrhythmic treatment are required. Ivabradine is a selective heart rate-reducing agent, an inhibitor of hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels, currently approved for treatment of coronary artery disease and chronic heart failure. In this review, we focus on the clinical and basic science evidence for the antiarrhythmic and proarrhythmic effects of ivabradine. We attempt to dissect the mechanisms behind the effects of ivabradine and indicate the focus of future studies.

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

Heart Rhythm: 14 Mar 2021; epub ahead of print
Marciszek M, Paterek A, Oknińska M, Zambrowska Z, Mackiewicz U, Mączewski M
Heart Rhythm: 14 Mar 2021; epub ahead of print | PMID: 33737235
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Impact:
Abstract

Arrhythmia-induced cardiomyopathy: A potentially reversible cause of refractory cardiogenic shock requiring venoarterial extracorporeal membrane oxygenation.

Hékimian G, Paulo N, Waintraub X, Bréchot N, ... Gandjbakhch E, Luyt CE
Background
The most severe form of arrhythmia-induced cardiomyopathy in adults- refractory cardiogenic shock requiring mechanical circulatory support-has rarely been reported.
Objective
The purpose of this study was to describe the management of critically ill patients admitted for acute, nonischemic, or worsening of previously known cardiac dysfunction and recent-onset supraventricular arrhythmia who developed refractory cardiogenic shock requiring venoarterial extracorporeal membrane oxygenation (VA-ECMO).
Methods
This study is a retrospective analysis of prospectively collected data.
Results
Between 2004 and 2018, 35 patients received VA-ECMO for acute, nonischemic cardiogenic shock and recent supraventricular arrhythmia (77% atrial fibrillation [AF]). Cardiogenic shock was the first disease manifestation in 21 patients (60%). Characteristics at ECMO implantation [median (interquartile range)] were Sequential Organ Failure Assessment score 10 (7-13); inotrope score 29 (11-80); left ventricular ejection (LVEF) fraction 10% (10%-15%); and lactate level 8 (4-11) mmol/L. For 12 patients, amiodarone and/or electric cardioversion successfully reduced arrhythmia, improved LVEF, and enabled weaning off VA-ECMO; 11 had long-term survival without transplantation or long-term assist device. Eight patients experiencing arrhythmia-reduction failure underwent ablation procedures (7 atrioventricular node [AVN] with pacing, 1 atrial tachycardia) were weaned off VA-ECMO; 7 survived. Of the remaining 15 patients without arrhythmia reduction or ablation, only the 6 bridged to heart transplantation or left ventricular (LV) assist device survived.
Conclusion
Arrhythmia-induced cardiomyopathy, mainly AF-related, is an underrecognized cause of refractory cardiogenic shock and should be considered in patients with nonischemic cardiogenic shock and recent-onset supraventricular arrhythmia. VA-ECMO support allowed safe arrhythmia reduction or rate control by AVN ablation while awaiting recovery, even among those with severe LV dilation.

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

Heart Rhythm: 11 Mar 2021; epub ahead of print
Hékimian G, Paulo N, Waintraub X, Bréchot N, ... Gandjbakhch E, Luyt CE
Heart Rhythm: 11 Mar 2021; epub ahead of print | PMID: 33722763
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Impact:
Abstract

Major adverse clinical events associated with implantation of a leadless intracardiac pacemaker.

Hauser RG, Gornick CC, Abdelhadi RH, Tang CY, Casey SA, Sengupta JD
Background
Leadless intracardiac pacemakers were developed to avoid the complications of transvenous pacing systems. The Medtronic Micra™ transcatheter pacemaker is one such system. We found an unexpected number of major adverse clinical events (MACE) in the Food and Drug Administration\'s Manufacturers and User Facility Device Experience (MAUDE) database associated with Micra implantation.
Objective
The purpose of this study was to describe these MACE and compare them to implant procedure MACE in MAUDE for Medtronic CapSureFix™ active-fixation transvenous pacing leads.
Methods
During January 2021, we queried the MAUDE database for reports of MACE for Micra pacemakers and CapSureFix leads using the simple search terms \"death,\" \"tamponade,\" and \"perforation.\" Reports from 2016-2020 were included.
Results
The search identified 363 MACE for Micra and 960 MACE for CapSureFix leads, including 96 Micra deaths (26.4%) vs 23 CapSureFix deaths (2.4%) (P <.001); 287 Micra tamponades (79.1%) vs 225 tamponades for CapSureFix (23.4%) (P <.001); and 99 rescue thoracotomies for Micra (27.3%) vs 50 rescue thoracotomies for CapSureFix (5.2%) (P <.001). More Micra patients required cardiopulmonary resuscitation (21.8% vs 1.1%) and suffered hypotension or shock (22.0% vs 5.8%) than CapSureFix recipients (P <.001). Micra patients were more likely to survive a myocardial perforation or tear if they had surgical repair (P = .014).
Conclusion
Micra leadless pacemaker implantation may be complicated by myocardial and vascular perforations and tears that result in cardiac tamponade and death. We estimate the incidence is low (<1%). Rescue surgery to repair perforations may be lifesaving. MACE are significantly less for implantation of CapSureFix transvenous ventricular pacing leads.

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

Heart Rhythm: 10 Mar 2021; epub ahead of print
Hauser RG, Gornick CC, Abdelhadi RH, Tang CY, Casey SA, Sengupta JD
Heart Rhythm: 10 Mar 2021; epub ahead of print | PMID: 33713856
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Impact:
Abstract

Gender-affirming hormone treatment causes changes in gender phenotype in a 12-lead electrocardiogram.

Saito N, Nagahara D, Ichihara K, Masumori N, Miura T, Takahashi S
Background
Men and women have specific patterns in an electrocardiogram (ECG) differentiated by J-point elevation and ST angle. Although gender-affirming hormone treatment is one of the treatments for gender dysphoria, its influence on an ECG has not been clarified yet.
Objective
The purpose of this study was to investigate ECG changes induced by gender-affirming hormone treatment.
Methods
The study population consisted of 29 transgender males and 8 transgender females and 37 age- and sex-matched cisgender females and males. Male pattern was defined as J-point elevation > 0.1 mV and ST angle > 20° in precordial leads.
Results
In the comparison between 29 transgender males and cisgender females, the prevalence of the male pattern (89.7% vs 6.9%; P < .001), prevalence of the early repolarization pattern (51.7% vs 17.2%; P = .01), J-point elevation (leads V1-V6), T-wave amplitudes (leads V1-V6), QRS amplitudes (leads II, III, V1-V6), and P-wave amplitudes (leads V1-V3) were significantly higher in transgender males. The prevalence of the male pattern was lower in transgender females than in cisgender males (25.0% vs 87.5%; P = .04). In the analysis of transgender males for whom ECGs were available before and after gender-affirming hormone treatment (n = 13), J-point elevation and T-wave amplitudes significantly increased after gender-affirming hormone treatment, leading to a higher prevalence of the male pattern (23.1% vs 92.3%; P < .001). The prevalence of the early repolarization pattern and QRS amplitudes also significantly increased after the treatment, but the augmentation of P-wave amplitudes was modest.
Conclusion
Gender-affirming hormone treatment for gender dysphoria is accompanied by a change in ECG phenotype toward affirming gender, in which change in androgen level may be involved.

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

Heart Rhythm: 07 Mar 2021; epub ahead of print
Saito N, Nagahara D, Ichihara K, Masumori N, Miura T, Takahashi S
Heart Rhythm: 07 Mar 2021; epub ahead of print | PMID: 33706005
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Impact:
Abstract

Competing risks in patients with primary prevention implantable cardioverter-defibrillators: Global Electrical Heterogeneity and Clinical Outcomes (GEHCO) study.

Waks JW, Haq KT, Tompkins C, Rogers AJ, ... Chugh SS, Tereshchenko LG
Background
Global electrical heterogeneity (GEH) is associated with sudden cardiac death in the general population. Its utility in patients with systolic heart failure who are candidates for primary prevention (PP) implantable cardioverter-defibrillators (ICDs) is unclear.
Objective
This purpose of this study was to investigate whether GEH is associated with sustained ventricular tachycardia/ventricular fibrillation leading to appropriate ICD therapies in patients with heart failure and PP ICDs.
Methods
We conducted a multicenter retrospective cohort study. GEH was measured by spatial ventricular gradient (SVG) direction (azimuth and elevation) and magnitude, QRS-T angle, and sum absolute QRST integral on preimplant 12-lead electrocardiograms. Survival analysis using cause-specific hazard functions compared the strength of associations with 2 competing outcomes: sustained ventricular tachycardia/ventricular fibrillation leading to appropriate ICD therapies and all-cause death without appropriate ICD therapies.
Results
We analyzed 2668 patients (mean age 63 ± 12 years; 23% female; 78% white; 43% nonischemic cardiomyopathy; left ventricular ejection fraction 28% ± 11% from 6 academic medical centers). After adjustment for demographic, clinical, device, and traditional electrocardiographic characteristics, SVG elevation (hazard ratio [HR] per 1SD 1.14; 95% confidence interval [CI] 1.04-1.25; P = .004), SVG azimuth (HR per 1SD 1.12; 95% CI 1.01-1.24; P = .039), SVG magnitude (HR per 1SD 0.75; 95% CI 0.66-0.85; P < .0001), and QRS-T angle (HR per 1SD 1.21; 95% CI 1.08-1.36; P = .001) were associated with appropriate ICD therapies. Sum absolute QRST integral had different associations in infarct-related cardiomyopathy (HR 1.29; 95% CI 1.04-1.60) and nonischemic cardiomyopathy (HR 0.78; 95% CI 0.62-0.96) (Pinteraction = .022).
Conclusion
In patients with PP ICDs, GEH is independently associated with appropriate ICD therapies. The SVG vector points in distinctly different directions in patients with 2 competing outcomes.

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

Heart Rhythm: 05 Mar 2021; epub ahead of print
Waks JW, Haq KT, Tompkins C, Rogers AJ, ... Chugh SS, Tereshchenko LG
Heart Rhythm: 05 Mar 2021; epub ahead of print | PMID: 33684549
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Impact:
Abstract

Skin sympathetic nerve activity as a biomarker for neurologic recovery during therapeutic hypothermia for cardiac arrest.

Kutkut I, Uceda D, Kumar A, Wong J, ... Chen PS, Everett TH
Background
Targeted temperature management (TTM) improves neurologic outcome after cardiac arrest. However, better neurologic prognostication is needed.
Objective
The purpose of this study was to test the hypothesis that noninvasive recording of skin sympathetic nerve activity (SKNA) and its association with heart rate (HR) during TTM may serve as a biomarker of neurologic status.
Methods
SKNA recordings were analyzed from 29 patients undergoing TTM. Patients were grouped based on Clinical Performance Category (CPC) score into group 1 (CPC 1-2) representing a good neurologic outcome and group 2 (CPC 3-5) representing a poor neurologic outcome.
Results
Of the 29 study participants, 18 (62%) were deemed to have poor neurologic outcome. At all timepoints, low average skin sympathetic nerve activity (aSKNA) was associated with poor neurologic outcome (odds ratio 22.69; P = .002) and remained significant (P = .03) even when adjusting for presenting clinical factors. The changes in aSKNA and HR during warming in group 1 were significantly correlated (ρ = 0.49; P <.001), even when adjusting for corresponding temperature and mean arterial pressure measurements (P = .017), whereas this correlation was not observed in group 2. Corresponding to high aSKNA, there was increased nerve burst activity during warming in group 1 compared to group 2 (0.739 ± 0.451 vs 0.176 ± 0.231; P = .013).
Conclusion
Neurologic recovery was retrospectively associated with SKNA. Patients undergoing TTM who did not achieve neurologic recovery were associated with low SKNA and lacked a significant correlation between SKNA and HR. These preliminary results indicate that SKNA may potentially be a useful biomarker to predict neurologic status in patients undergoing TTM.

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

Heart Rhythm: 05 Mar 2021; epub ahead of print
Kutkut I, Uceda D, Kumar A, Wong J, ... Chen PS, Everett TH
Heart Rhythm: 05 Mar 2021; epub ahead of print | PMID: 33689908
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Impact:
Abstract

Percentage of age-predicted cardiorespiratory fitness and risk of sudden cardiac death: A prospective cohort study.

Laukkanen JA, Kurl S, Khan H, Kunutsor SK
Background
The inverse associations between cardiorespiratory fitness (CRF) and vascular outcomes have been established. However, there has been no prospective evaluation of the relationship between percentage of age-predicted cardiorespiratory fitness (%age-predicted CRF) and risk of sudden cardiac death (SCD).
Objective
The purpose of this study was to assess the association of %age-predicted CRF with SCD risk in a long-term prospective cohort study.
Methods
CRF was assessed using the gold standard respiratory gas exchange analyzer in 2276 men who underwent cardiopulmonary exercise testing. The age-predicted CRF estimated from a regression equation for age was converted to %age-predicted CRF using (Achieved CRF/Age-predicted CRF) × 100. Hazard ratios (HRs) [95% confidence intervals (CIs)] were calculated for SCD.
Results
During median follow-up of 28.2 years, 260 SCDs occurred. There was a dose-response relationship between age-predicted CRF and SCD. A 1-SD increase in %age-predicted CRF was associated with a decreased risk of SCD in analysis adjusted for established risk factors (HR 0.60; 95% CI 0.53-0.70), which remained consistent on further adjustment for several potential confounders, including alcohol consumption, physical activity, socioeconomic status, and systemic inflammation (HR 0.73; 95% CI 0.62-0.85). The corresponding adjusted HRs were 0.34 (0.23-0.50) and 0.52 (0.34-0.79), respectively, when comparing extreme quartiles of %age-predicted CRF levels. HRs for the associations of absolute CRF levels with SCD risk in the same participants were similar.
Conclusion
Percentage of age-predicted CRF is continuously, strongly, and independently associated with risk of SCD and is comparable to absolute CRF as a risk indicator for SCD.

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

Heart Rhythm: 05 Mar 2021; epub ahead of print
Laukkanen JA, Kurl S, Khan H, Kunutsor SK
Heart Rhythm: 05 Mar 2021; epub ahead of print | PMID: 33689907
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Impact:
Abstract

Tumescent local anesthesia versus general anesthesia for subcutaneous implantable cardioverter-defibrillator implantation.

Romero J, Bello J, Díaz JC, Grushko M, ... Natale A, Di Biase L
Background
Subcutaneous implantable cardioverter-defibrillator (S-ICD) is an effective alternative to transvenous implantable cardioverter-defibrillator. General anesthesia (GA) is considered the standard sedation approach because of the pain caused by the manipulation of subcutaneous tissue with S-ICD implantation. However, GA carries several limitations, including additional risk of adverse events, prolonged in-room times, and increased costs.
Objective
The purpose of this study was to define the effectiveness and safety of tumescent local anesthesia (TLA) in comparison to GA in patients undergoing S-ICD implantation.
Methods
We performed a prospective, nonrandomized, controlled, multicenter study of patients referred for S-ICD implantation between 2019 and 2020. Patients were allocated to either TLA or GA on the basis of patient\'s preferences and/or anesthesia service availability. TLA was prepared using lidocaine, epinephrine, sodium bicarbonate, and sodium chloride. All patients provided written informed consent, and the institutional review board at each site provided approval for the study.
Results
Sixty patients underwent successful S-ICD implantation from July 2019 to November 2020. Thirty patients (50%) received TLA, and the rest GA. There were no differences between groups with regard to baseline characteristics. In-room and procedural times were significantly shorter with TLA (107.6 minutes vs 186 minutes; P < .0001 and 53.2 minutes vs 153.7 minutes; P < .0001, respectively). Pain was reported less frequently by patients who received TLA. The use of opioids was significantly reduced in patients who received TLA (23% vs 62%; P = .002).
Conclusion
TLA is an effective and safe alternative to GA in S-ICD implantation. The use of TLA is associated with shorter in-room and procedural times, less postprocedural pain, and reduced usage of opioids for analgesia.

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

Heart Rhythm: 04 Mar 2021; epub ahead of print
Romero J, Bello J, Díaz JC, Grushko M, ... Natale A, Di Biase L
Heart Rhythm: 04 Mar 2021; epub ahead of print | PMID: 33684548
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Impact:
Abstract

Comparison of the effect of glucose-lowering agents on the risk of atrial fibrillation: A network meta-analysis.

Wence S, Wenchang Z, Da Z, Ge R, ... Haonan C, Chunhua D
Background
Diabetes is associated with the progression of atrial fibrillation (AF) and atrial flutter (AFL). However, whether glucose-lowering agents could reduce AF/AFL remains unclear. We hypothesized that different glucose-lowering agents exhibit different characteristic effects on the risk of AF/AFL.
Objectives
The goals of this study were to evaluate the effect of different glucose-lowering agents and identify the optimal treatment that can reduce AF/AFL events in patients with diabetes.
Methods
We searched PubMed, Embase, and the Cochrane Library from their inception to September 30, 2020. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were used in this network meta-analysis. The primary end point of our study was AF or AFL. Only studies that reported AF/AFL as clinical end points with a follow-up period of at least 12 months were included. The results from trials were presented as odds ratios (ORs) with 95% confidence intervals (CIs). The results were pooled using a Bayesian random-effects model.
Results
Five eligible studies (9 glucose-lowering agents, including thiazolidinedione, metformin, sulfonylurea, insulin, dipeptidyl peptidase-4 inhibitor, glucagon-like peptide-1 receptor agonist [GLP-1RA], sodium-glucose cotransporter 2 inhibitor, alpha-glucosidase inhibitor, and non-sulfonylurea) consisting of 263,583 patients with type 2 diabetes mellitus were included. Based on the pooled results, GLP1-RA significantly reduced AF/AFL events compared with metformin (OR 0.17; 95% CI 0.04-0.61), sulfonylurea (OR 0.23; 95% CI 0.07-0.73), insulin (OR 0.20; 95% CI 0.07-0.86), and non-sulfonylurea (OR 0.18; 95% CI 0.04-0.66).
Conclusion
Compared with other glucose-lowering agents, GLP1-RA could reduce the risk of AF/AFL in patients with diabetes.

Copyright © 2021. Published by Elsevier Inc.

Heart Rhythm: 04 Mar 2021; epub ahead of print
Wence S, Wenchang Z, Da Z, Ge R, ... Haonan C, Chunhua D
Heart Rhythm: 04 Mar 2021; epub ahead of print | PMID: 33684547
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Impact:
Abstract

Physiology-based electrocardiographic criteria for left bundle branch capture.

Jastrzębski M, Kiełbasa G, Curila K, Moskal P, ... Rajzer M, Vijayaraman P
Background
During left bundle branch (LBB) area pacing, it is important to confirm that capture of the LBB, and not just capture of only adjacent left ventricular (LV) myocardium, has been achieved.
Objective
The purpose of this study was to establish electrocardiographic (ECG) criteria for LBB capture. We hypothesized that because LBB pacing results in physiological depolarization of the LV, then the native QRS can serve as a reference for diagnosis of LBB capture in the same patient.
Methods
Only patients with evidence of LBB capture (QRS morphology transition) were included. Several QRS characteristics were compared between the native rhythm and different types of LBB area capture.
Results
A total of 357 ECGs (124 patients) were analyzed: 118 with native rhythm, 124 with nonselective LBB capture, 69 with selective LBB capture, and 46 with LV septal capture. Our hypotheses that during LBB capture the paced V6 R-wave peak time (RWPT; measured from QRS onset) equals the native V6 RWPT and that the paced V6 RWPT (measured from the stimulus) equals the LBB potential to V6 R-wave peak interval were positively validated. Criteria based on these rules had sensitivity and specificity of 88.2%-98.0% and 85.7%-95.4%, respectively. Moreover, 100% specific V6 RWPT cutoff for LBB capture diagnosis in patients with narrow QRS/right bundle branch block was determined to be 74 ms.
Conclusion
We showed equivalency of LV activation times on ECG during native and paced LBB conduction. Therefore, if V6 RWPT is longer during pacing, this finding is indicative of lack of LBB capture.

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

Heart Rhythm: 03 Mar 2021; epub ahead of print
Jastrzębski M, Kiełbasa G, Curila K, Moskal P, ... Rajzer M, Vijayaraman P
Heart Rhythm: 03 Mar 2021; epub ahead of print | PMID: 33677102
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Impact:
Abstract

Three-dimensional guided selective right ventricular septal pacing preserves ventricular systolic function and synchrony in pediatric patients.

Silvetti MS, Pazzano V, Battipaglia I, Saputo FA, ... Ravà L, Drago F
Background
Nonfluoroscopic 3-dimensional (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
The purpose of this study was to determine whether 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 was performed. A 3D pacing map guided ventricular lead implantation at septal sites with narrow paced QRS. Serial echocardiograms were obtained after pacemaker implantation to monitor for function (volumes, ejection fraction [EF], global longitudinal/circumferential strain) and synchrony (interventricular mechanical delay, septal to posterior wall motion delay, systolic dyssynchrony index). Data are reported as median (25th-75th percentile).
Results
Thirty-two CAVB patients (age 9.8 [7.0-14.0] years; 11 with a previous pacing system) underwent selective RV septal pacing (13 DDD, 19 VVIR pacemaker; midseptum 22, parahisian 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 parahisian 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 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Heart Rhythm: 27 Feb 2021; 18:434-442
Silvetti MS, Pazzano V, Battipaglia I, Saputo FA, ... Ravà L, Drago F
Heart Rhythm: 27 Feb 2021; 18:434-442 | PMID: 33307214
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Impact:
Abstract

Cybersecurity: The need for data and patient safety with cardiac implantable electronic devices.

Das S, Siroky GP, Lee S, Mehta D, Suri R
Remote monitoring of cardiac implantable electronic devices (CIEDs) has become routine practice as a result of the advances in biomedical engineering, the advent of interconnectivity between the devices through the Internet, and the demonstrated improvement in patient outcomes, survival, and hospitalizations. However, this increased dependency on the Internet of Things comes with risks in the form of cybersecurity lapses and possible attacks. Although no cyberattack leading to patient harm has been reported to date, the threat is real and has been demonstrated in research laboratory scenarios and echoed in patient concerns. The CIED universe comprises a complex interplay of devices, connectivity protocols, and sensitive information flow between the devices and the central cloud server. Various manufacturers use proprietary software and black-box connectivity protocols that are susceptible to hacking. Here we discuss the fundamentals of the CIED ecosystem, the potential security vulnerabilities, a historical overview of such vulnerabilities reported in the literature, and recommendations for improving the security of the CIED ecosystem and patient safety.

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

Heart Rhythm: 27 Feb 2021; 18:473-481
Das S, Siroky GP, Lee S, Mehta D, Suri R
Heart Rhythm: 27 Feb 2021; 18:473-481 | PMID: 33059076
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Impact:
Abstract

Repeated exposure to transient obstructive sleep apnea-related conditions causes an atrial fibrillation substrate in a chronic rat model.

Linz B, Hohl M, Lang L, Wong DWL, ... Böhm M, Linz D
Background
High night-to-night variability in obstructive sleep apnea (OSA) is associated with atrial fibrillation (AF). Obstructive apneas are characterized by intermittent deoxygenation-reoxygenation and intrathoracic pressure swings during ineffective inspiration against occluded upper airways.
Objective
We elucidated the effect of repeated exposure to transient OSA conditions simulated by intermittent negative upper airway pressure (INAP) on the development of an AF substrate.
Methods
INAP (48 events/4 h; apnea-hypopnea index 12 events/h) was applied in sedated spontaneously breathing rats (2% isoflurane) to simulate mild-to-moderate OSA. Rats without INAP served as a control group (CTR). In an acute test series (ATS), rats were either killed immediately (n = 9 per group) or after 24 hours of recovery (ATS-REC: n = 5 per group). To simulate high night-to-night variability in OSA, INAP applications (n = 10; 24 events/4 h; apnea-hypopnea index 6/h) were repeated every second day for 3 weeks in a chronic test series (CTS).
Results
INAP increased atrial oxidative stress acutely, represented in decreases of reduced to oxidized glutathione ratio (ATS: INAP: 0.33 ± 0.05 vs CTR: 1 ± 0.26; P = .016), which was reversible after 24 hours (ATS-REC: INAP vs CTR; P = .274). Although atrial oxidative stress did not accumulate in the CTS, atrial histological analysis revealed increased cardiomyocyte diameters, reduced connexin 43 expression, and increased interstitial fibrosis formation (CTS: INAP 7.0% ± 0.5% vs CTR 5.1% ± 0.3%; P = .013), which were associated with longer inducible AF episodes (CTS: INAP: 11.65 ± 4.43 seconds vs CTR: 0.7 ± 0.33 seconds; P = .033).
Conclusion
Acute simulation of OSA was associated with reversible atrial oxidative stress. Cumulative exposure to these transient OSA-related conditions resulted in AF substrates and was associated with increased AF susceptibility. Mild-to-moderate OSA with high night-to-night variability may deserve intensive management to prevent atrial substrate development.

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

Heart Rhythm: 27 Feb 2021; 18:455-464
Linz B, Hohl M, Lang L, Wong DWL, ... Böhm M, Linz D
Heart Rhythm: 27 Feb 2021; 18:455-464 | PMID: 33080392
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Impact:
Abstract

Identification of important risk factors for all-cause mortality of acquired long QT syndrome patients using random survival forests and non-negative matrix factorization.

Chen C, Zhou J, Yu H, Zhang Q, ... Tse G, Xia Y
Background
Acquired long QT syndrome (aLQTS) is often associated with poor clinical outcomes.
Objective
The purpose of this study was to examine the important predictors of all-cause mortality of aLQTS patients by applying both random survival forest (RSF) and non-negative matrix factorization (NMF) analyses.
Methods
Clinical characteristics and manually measured electrocardiographic (ECG) parameters were initially entered into the RSF model. Subsequently, latent variables identified using NMF were entered into the RSF as additional variables. The primary outcome was all-cause mortality.
Results
A total of 327 aLQTS patients were included. The RSF model identified 16 predictive factors with positive variable importance values: cancer, potassium, RR interval, calcium, age, JT interval, diabetes mellitus, QRS duration, QTp interval, chronic kidney disease, QTc interval, hypertension, QT interval, female, JTc interval, and cerebral hemorrhage. Increasing the number of latent features between ECG indices, which incorporated from n = 0 to n = 4 by NMF, maximally improved the prediction ability of the RSF-NMF model (C-statistic 0.77 vs 0.89).
Conclusion
Cancer and serum potassium and calcium levels can predict all-cause mortality of aLQTS patients, as can ECG indicators including JTc and QRS. The present RSF-NMF model significantly improved mortality prediction.

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

Heart Rhythm: 27 Feb 2021; 18:426-433
Chen C, Zhou J, Yu H, Zhang Q, ... Tse G, Xia Y
Heart Rhythm: 27 Feb 2021; 18:426-433 | PMID: 33127541
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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: 27 Feb 2021; 18:360-365
Squara F, Elbaum C, Garret G, Liprandi L, ... Moceri P, Ferrari E
Heart Rhythm: 27 Feb 2021; 18:360-365 | PMID: 33181323
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Impact:
Abstract

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

Pambrun T, Duchateau J, Delgove A, Denis A, ... Walton RD, Derval N
Background
Gaps in the roof line have been ascribed to epicardial conduction using the septopulmonary bundle.
Objectives
We sought to evaluate the frequency of septopulmonary bundle bypass during roof line 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 roof line 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 roof lines than floor lines (33% vs 15%; P = .049). Electrogram morphologies, activation sequences, and pacing maneuvers indicated an epicardial bypass of the roof line 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 roof line 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 roof line ablation.

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

Heart Rhythm: 27 Feb 2021; 18:349-357
Pambrun T, Duchateau J, Delgove A, Denis A, ... Walton RD, Derval N
Heart Rhythm: 27 Feb 2021; 18:349-357 | PMID: 33188900
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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: 27 Feb 2021; 18:382-391
Rordorf R, Casula M, Pezza L, Fortuni F, ... Savastano S, Vicentini A
Heart Rhythm: 27 Feb 2021; 18:382-391 | PMID: 33212250
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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 patients in which TLE was performed for symptomatic SVC syndrome. Patient characteristics, extraction details, percutaneous management of SVC occlusions, and clinical follow up 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 9 (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: 27 Feb 2021; 18:392-398
Gabriels J, Chang D, Maytin M, Tadros T, ... Eisenhauer A, Epstein LM
Heart Rhythm: 27 Feb 2021; 18:392-398 | PMID: 33212249
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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 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: 27 Feb 2021; 18:443-452
Suzuki A, Lehmann HI, Wang S, Monahan KH, ... Curley MG, Packer DL
Heart Rhythm: 27 Feb 2021; 18:443-452 | PMID: 33212248
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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 VAs ≥ 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 VAs ≥ 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: 27 Feb 2021; 18:399-403
Schuger C, Daubert JP, Zareba W, Rosero S, ... McNitt S, Kutyifa V
Heart Rhythm: 27 Feb 2021; 18:399-403 | PMID: 33232811
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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: 27 Feb 2021; 18:366-373
Calkins H, Gache L, Frame D, Boo LM, ... Duytschaever M, Packer DL
Heart Rhythm: 27 Feb 2021; 18:366-373 | 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 tachyarrhythmias (PATs) 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: 27 Feb 2021; 18:465-472
Liu X, Yuan Y, Wong J, Meng G, ... Everett TH, Chen PS
Heart Rhythm: 27 Feb 2021; 18:465-472 | PMID: 33246037
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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 Prospective Registry of Patients Using the Wearable Cardioverter Defibrillator (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 arrhythmic 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 arrhythmic 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: 27 Feb 2021; 18:404-410
Goldenberg I, Erath JW, Russo AM, Burch AE, ... McNitt S, Kutyifa V
Heart Rhythm: 27 Feb 2021; 18:404-410 | PMID: 33248269
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Impact:
Abstract

Prognostic value of implantable defibrillator-computed respiratory disturbance index: The DASAP-HF study.

Boriani G, Pisanò ECL, Pieragnoli P, Locatelli A, ... Ricci RP, D\'Onofrio A
Background
Sleep apnea, as measured by polysomnography, is associated with adverse outcomes in heart failure. The DASAP-HF (Diagnosis and Treatment of Sleep Apnea in Patient With Heart Failure) study previously demonstrated that the respiratory disturbance index (RDI) computed by the ApneaScan algorithm (Boston Scientific) accurately identifies severe sleep apnea in implantable cardioverter-defibrillator (ICD) patients.
Objective
The purpose of the long-term study phase was to assess the incidence of clinical events after 24 months and investigate the association with RDI values.
Methods
Patients with left ventricular ejection fraction ≤35% implanted with an ICD were enrolled and followed-up for 24 months. The RDI calculated at 1 month after implantation was used to stratify patients (below or above 30 episodes/h). The endpoints were all-cause death and a combination of all-cause death or cardiovascular hospitalization.
Results
Of the 265 enrolled patients, 224 had usable RDI values. Severe sleep apnea (RDI ≥30 episodes/h) was diagnosed in 115 patients (51%). These patients were more frequently male (84% vs 72%; P = .030) and had higher creatinine levels. During median follow-up of 25 months, 19 patients (8%) died. Cardiovascular hospitalizations were reported in 19 patients (8%). The risk of all-cause death was higher in patients with RDI ≥30 episodes/h (hazard ratio [HR] 3.33; 95% confidence interval [CI] 1.35-8.21; P = .023), as well as the risk of all-cause death or cardiovascular hospitalization (HR 1.94; 95% CI 1.01-3.76; P = .048). At multivariate analysis, independent predictors of death were RDI ≥30 episodes/h (HR 4.02; 95% CI 1.16-13.97; P = .029) and creatinine levels (HR 2.36; 95% CI 1.26-4.42; P = .008).
Conclusion
In heart failure patients implanted with an ICD, higher RDI values are associated with death and cardiovascular hospitalizations. Device-detected severe sleep apnea independently predicts death.

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

Heart Rhythm: 27 Feb 2021; 18:374-381
Boriani G, Pisanò ECL, Pieragnoli P, Locatelli A, ... Ricci RP, D'Onofrio A
Heart Rhythm: 27 Feb 2021; 18:374-381 | PMID: 33283757
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Impact:
Abstract

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

Zoni-Berisso M, 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 implantable cardioverter-DEfibrillator 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 (63-78)); 750 (76%) were men, 537 (55%) had ischemic cardiomyopathy; 460 (47%) were implanted 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/m2, 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: 27 Feb 2021; 18:411-418
Zoni-Berisso M, Martignani C, Ammendola E, Narducci ML, ... Malacrida M, Biffi M
Heart Rhythm: 27 Feb 2021; 18:411-418 | PMID: 33249200
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Impact:
Abstract

Relationship between device-detected burden and duration of atrial fibrillation and risk of ischemic stroke.

Al-Gibbawi M, Ayinde HO, Bhatia NK, El-Chami MF, ... Merchant FM, Kiani S
Background
Wider availability of continuous rhythm monitoring has made feasible the incorporation of metrics of atrial fibrillation (AF) burden and duration into the decision to initiate anticoagulation. However, the relationship between thresholds of burden and duration and underlying risk factors at which anticoagulation should be considered remains unclear.
Objective
The purpose of this study was to evaluate the relationships of these metrics with each other and the outcome of stroke/transient ischemic attack (TIA).
Methods
We identified patients with cardiovascular implantable electronic devices (CIEDs) with atrial leads who had at least 1 interrogation in 2016 demonstrating nonpermanent AF and were not receiving oral anticoagulation (OAC). We evaluated the relationship between burden (ie, percentage of time spent in AF), the longest single episode of AF, and risk factors (ie, CHA2DS2-VASc score) in predicting risk of stroke/TIA.
Results
The study included 384 patients with mean follow-up of 3.2 ± 0.8 years and incidence of stroke/TIA of 14.8% during follow-up (∼4.6% per year). The burden of AF and the duration of longest episode demonstrated a significant positive correlation to each other but not CHA2DS2-VASc score. Importantly, although the CHA2DS2-VASc score was predictive of stroke/TIA, neither burden nor duration was associated with stroke/TIA.
Conclusion
Among patients with CIED-detected AF not receiving OAC, the amount of AF (measured by either burden or duration) does not seem to significantly impact stroke risk, whereas CHA2DS2-VASc score does. These data suggest that among patients with CIED-detected AF, once AF occurs, stroke risk seems to be predominantly driven by underlying risk factors.

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

Heart Rhythm: 27 Feb 2021; 18:338-346
Al-Gibbawi M, Ayinde HO, Bhatia NK, El-Chami MF, ... Merchant FM, Kiani S
Heart Rhythm: 27 Feb 2021; 18:338-346 | PMID: 33250442
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Impact:
Abstract

Intraprocedural dynamics of cardiac conduction during transcatheter aortic valve implantation: Assessment by simultaneous electrophysiological testing.

Reiter C, Lambert T, Kellermair J, Blessberger H, ... Nahler A, Steinwender C
Background
Transcatheter aortic valve implantation (TAVI) is an established treatment for patients with severe aortic stenosis and high to intermediate surgical risk. However, the proximity of the conduction system to the prosthesis landing zone bears the risk of atrioventricular conduction disorders. The underlying pathophysiology is not fully understood.
Objective
The purpose of this study was to characterize the impact of TAVI on the conduction system as assessed by simultaneous electrophysiological testing.
Methods
AH and HV intervals and QRS duration were measured using a quadripolar His catheter and surface electrocardiogram in 108 patients at baseline (BL), after balloon predilation (timepoint 1 [T1]), after implantation of the valve prosthesis (T2), and after postdilation, if deemed necessary (T3).
Results
Between BL and T2, significant increases of HV interval and QRS duration were observed, with a mean delta of +12.4 ms and +32.7 ms, respectively. Both balloon predilation and valve implantation had an impact on infranodal conduction. No significant increase of AH intervals was documented. The increase of QRS duration led to left bundle branch block (LBBB) in 57 patients (52.8%). Implantation depth positively correlated with QRS prolongation (ρ = 0.21, P = .042) but not with changes of AH or HV interval (ρ = -0.03, P = .762; and ρ = 0.15, P = .130, respectively).
Conclusion
Electrophysiological testing during TAVI shows impairment of infranodal atrioventricular conduction by balloon predilation and valve implantation. This impairment is positively correlated with valve implantation depth and results in an increase of QRS duration with mainly LBBB pattern on surface electrocardiogram.

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

Heart Rhythm: 27 Feb 2021; 18:419-425
Reiter C, Lambert T, Kellermair J, Blessberger H, ... Nahler A, Steinwender C
Heart Rhythm: 27 Feb 2021; 18:419-425 | PMID: 33250391
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Impact:
Abstract

Does pulsed field ablation regress over time? A quantitative temporal analysis of pulmonary vein isolation.

Kawamura I, Neuzil P, Shrivamurthy P, Petru J, ... Koruth JS, Reddy VY
Background
The tissue specificity of pulsed field ablation (PFA) makes it an attractive energy source for pulmonary vein (PV) isolation (PVI). However, beyond each PFA lesion\'s zone of irreversible electroporation and cell death, there may be a surrounding zone of reversible electroporation and cell injury that could potentially normalize with time.
Objective
The purpose of this study was to assess whether the level of electrical PVI that is observed acutely after PFA regresses over time.
Methods
In a clinical trial, patients with paroxysmal atrial fibrillation underwent PVI using a biphasic PFA waveform delivered through a dedicated, variably deployable multielectrode basket/flower catheter. Detailed voltage maps were created using a multispline diagnostic catheter immediately after PFA and again ∼3 months later in a prospective, protocol-specified reassessment procedure. We analyzed 20 patients who underwent PFA with durable PVI and available maps from both time points. To compare the ablated zones, the left- and right-sided PV antral isolation areas and nonablated posterior wall area were quantified and the distances between left and right PV low-voltage edges were measured.
Results
A comparison of voltage maps immediately after PFA and at a median of 84 days (interquartile range 69-90 days) later revealed that there was no significant difference in either the left- and right-sided PV antral isolation areas or nonablated posterior wall area. The distances between low-voltage edges on the posterior wall were also not significantly different between the 2 time points.
Conclusion
This study demonstrates that the level of PV antral isolation after PFA with a multielectrode PFA catheter persists without regression.

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

Heart Rhythm: 26 Feb 2021; epub ahead of print
Kawamura I, Neuzil P, Shrivamurthy P, Petru J, ... Koruth JS, Reddy VY
Heart Rhythm: 26 Feb 2021; epub ahead of print | PMID: 33647464
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Abstract

Oral anticoagulants in extremely-high-risk, very elderly (>90 years) patients with atrial fibrillation.

Chao TF, Chiang CE, Chan YH, Liao JN, ... Lip GYH, Chen SA
Background
The prevalence and incidence of atrial fibrillation (AF) increase with age. However, older patients often are denied oral anticoagulation (OAC), especially if they are \"very elderly\" (age ≥90 years) and perceived to be high risk for bleeding, for example, those with a history of intracranial hemorrhage (ICH), gastrointestinal bleeding (GIB), or chronic kidney disease.
Objective
The purpose of this study was to investigate the effectiveness and safety of OAC in this high-risk, very elderly group.
Methods
We used the Taiwan National Health Insurance Research Database to identify high-risk, very elderly subjects taking OAC, either warfarin or a non-vitamin K antagonist oral anticoagulant (NOAC), and compared them to non-OAC users for the composite net clinical endpoint of ischemic stroke, ICH, major bleeding, or mortality.
Results
We studied 7362 subjects (mean age 92.5 years), of whom 1737 were taking NOACs, 670 warfarin, and 4955 non-OACs. Compared to non-OACs, warfarin was associated with a higher risk of the composite endpoint (adjusted hazard ratio [aHR] 1.163; 95% confidence interval [CI] 1.052-1.287), whereas NOACs were associated with a lower risk (aHR 0.763; 95% CI 0.702-0.830). After propensity matching, NOACs were associated with a lower risk of events compared to non-OACs or warfarin, whereas warfarin had a similar risk compared to non-OACs.
Conclusion
Warfarin was associated with a similar or even higher risk of composite clinical outcomes compared to non-OACs. NOACs were associated with a lower risk of composite endpoint compared to warfarin or non-OACs, and their use still should be considered in these high-risk, very elderly AF patients.

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

Heart Rhythm: 24 Feb 2021; epub ahead of print
Chao TF, Chiang CE, Chan YH, Liao JN, ... Lip GYH, Chen SA
Heart Rhythm: 24 Feb 2021; epub ahead of print | PMID: 33640447
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Impact:
Abstract

Arrhythmias and device therapies in patients with cancer therapy-induced cardiomyopathy.

Lee C, Maan A, Singh JP, Fradley MG
Our knowledge of associated cardiotoxicities from novel therapeutics in oncology continues to expand. These include arrhythmias from cancer-therapy induced cardiomyopathy resulting from both direct and indirect effects on cardiomyocytes and other mechanisms that can adversely impact cardiovascular outcomes and overall mortality. In this review, we focus on both the arrhythmias of various classes of oncologic agents as well as the use of cardiac implantable electronic devices (cardioverter-defibrillators, permanent pacemakers, and cardiac resynchronization therapy) in cardio-oncology patients.

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

Heart Rhythm: 24 Feb 2021; epub ahead of print
Lee C, Maan A, Singh JP, Fradley MG
Heart Rhythm: 24 Feb 2021; epub ahead of print | PMID: 33640446
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Impact:
Abstract

Ventricular tachycardia burden reduction after substrate ablation: Predictors of recurrence.

Quinto L, Sanchez-Somonte P, Alarcón F, Garre P, ... Mont L, Roca-Luque I
Background
Substrate-based ventricular tachycardia (VT) ablation is a first-line treatment in patients with structural cardiac disease and sustained VT refractory to medical therapy. Despite technological improvements and increased knowledge of VT substrate, recurrence still is frequent. Published data are lacking on the possible reduction in VT burden after ablation despite recurrence.
Objective
The purpose of this study was to assess VT burden reduction during long-term follow-up after substrate ablation and identify predictors of VT recurrence.
Methods
We analyzed 234 consecutive VT ablation procedures in 207 patients (age 63 ± 14.9 years; 92% male; ischemic heart disease in 65%) who underwent substrate ablation in a single center from 2013 to 2018.
Results
After follow-up of 3.14 ± 1.8 years, the VT recurrence rate was 41.4%. Overall, a 99.6% reduction in VT burden (median VT episodes per year: preprocedural 3.546 [1.347-13.951] vs postprocedural 0.001 [0-0.689]; P = .001) and a 96.3% decrease in implantable cardioverter-defibrillator (ICD) shocks (preprocedural 1.145 [0.118-4.467] vs postprocedural 0.042 [0-0.111] per year; P = .017) were observed. In the subgroup of patients who experienced VT recurrences, VT burden decreased by 69.2% (median VT episodes per year: preprocedural 2.876 [1.105-8.801] vs postprocedural 0.882 [0.505-2.283]; P <.001). Multivariable analysis showed persistence of late potentials (67% vs 19%; hazard ratio 3.18 [2.18-6.65]; P <.001) and lower left ventricular ejection fraction (EF) (30 [25-40] vs 39 [30-50]; P = .022) as predictors of VT recurrence.
Conclusion
Despite a high recurrence rate during long-term follow-up, substrate-based VT ablation is related to a large reduction in VT burden and a decrease in ICD therapies. Lower EF and persistence of late potentials are predictors of recurrence.

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

Heart Rhythm: 23 Feb 2021; epub ahead of print
Quinto L, Sanchez-Somonte P, Alarcón F, Garre P, ... Mont L, Roca-Luque I
Heart Rhythm: 23 Feb 2021; epub ahead of print | PMID: 33639298
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Impact:
Abstract

Absence of (sub-)acute cerebral events or lesions after electroporation ablation in the left-sided canine heart.

Neven K, Füting A, Byrd I, Heil RW, ... Donskoy E, Jensen JA
Background
Irreversible electroporation (IRE) is a nonthermal ablation modality. A 200-J application can create deep myocardial lesions, but gas bubbles are created at the ablation electrode. Cerebral effects of these bubbles are unknown.
Objective
The purpose of this study was to investigate gas microemboli-induced brain lesions after IRE and radiofrequency (RF) ablation to the left side of the canine heart, using magnetic resonance imaging (MRI) and histopathology.
Methods
In 11 canines, baseline cerebral MRI scans were performed. In 9 animals, after retrograde femoral artery access, 12 ± 4 200-J IRE applications were administered in the ascending aorta. In 2 animals, 30 minutes of irrigated 30-W RF ablation using 10-30g of contact force was applied in the left ventricle. At days 1 and 5 after ablation, MRI was repeated. The brain tissue then was histopathologically examined.
Results
All ablations and follow-up were uneventful. Intracardiac echography confirmed gas bubble formation after each IRE application. Neurologic examination was normal. MRI scans were normal in all animals at day 1 and were normal in 10 of 11 animals at day 5. In 1 animal, a single <2-mm-diameter lesion in the right temporal region could not be excluded as a small infarct or early hemorrhagic site. Histopathologic analysis of the same region showed no pathologic changes. In all other animals, gross and microscopic pathology were normal.
Conclusion
MRI images alone or in combination with histologic follow-up did not reveal treatment-related embolic events. Gross and microscopic pathology did not reveal evidence of treatment-related embolic events. IRE seems to be a safe ablation modality for the brain.

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

Heart Rhythm: 18 Feb 2021; epub ahead of print
Neven K, Füting A, Byrd I, Heil RW, ... Donskoy E, Jensen JA
Heart Rhythm: 18 Feb 2021; epub ahead of print | PMID: 33617997
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Impact:
Abstract

Individualized ablation strategy to treat persistent atrial fibrillation: Core-to-boundary approach guided by charge-density mapping.

Shi R, Chen Z, Pope MTB, Zaman JAB, ... Betts TR, Wong T
Background
Noncontact charge-density mapping allows rapid real-time global mapping of atrial fibrillation (AF), offering the opportunity for a personalized ablation strategy.
Objective
The purpose of this study was to compare the 2-year outcome of an individualized strategy consisting of pulmonary vein isolation (PVI) plus core-to-boundary ablation (targeting the conduction pattern core with an extension to the nearest nonconducting boundary) guided by charge-density mapping, with an empirical PVI plus posterior wall electrical isolation (PWI) strategy.
Methods
Forty patients (age 62 ± 12 years; 29 male) with persistent AF (10 ± 5 months) prospectively underwent charge-density mapping-guided PVI, followed by core-to-boundary stepwise ablation until termination of AF or depletion of identified cores. Freedom from AF/atrial tachycardia (AT) at 24 months was compared with a propensity score-matched control group of 80 patients with empirical PVI + PWI guided by conventional contact mapping.
Results
Acute AF termination occurred in 8 of 40 patients after charge-density mapping-guided PVI alone and in 21 of the remaining 32 patients after core-to-boundary ablation in the study cohort, compared with 8 of 80 (10%) in the control cohort (P <.001). On average, 2.2 ± 0.6 cores were ablated post-PVI before acute AF termination. At 24 months, freedom from AF/AT after a single procedure was 68% in the study group vs 46% in the control group (P = .043).
Conclusion
An individualized ablation strategy consisting of PVI plus core-to-boundary ablation guided by noncontact charge-density mapping is a feasible and effective strategy for treating persistent AF, with a favorable 24-month outcome.

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

Heart Rhythm: 18 Feb 2021; epub ahead of print
Shi R, Chen Z, Pope MTB, Zaman JAB, ... Betts TR, Wong T
Heart Rhythm: 18 Feb 2021; epub ahead of print | PMID: 33610744
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Impact:
Abstract

Optimizing lead placement for pacing in dyssynchronous heart failure: The patient in the lead.

Wouters PC, Vernooy K, Cramer MJ, Prinzen FW, Meine M
Cardiac resynchronization therapy (CRT) greatly reduces morbidity and mortality in patients with dyssynchronous heart failure. However, despite tremendous efforts, response has been variable and can be further improved. Although optimizing left ventricular lead placement (LVLP) is arguably the cornerstone of CRT, the procedure of LVLP using the transvenous approach has remained largely unchanged for more than 2 decades. Improvements have been developed using scar location and electrical and/or mechanical mapping. Interest in conduction system pacing as an alternative to biventricular pacing has emerged recently. Conduction system pacing is promising but may not be suitable for all patients with dyssynchronous heart failure. This review underscores the importance of a patient-tailored approach and discusses the potential applications of both conduction system pacing and targeted biventricular CRT.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Heart Rhythm: 15 Feb 2021; epub ahead of print
Wouters PC, Vernooy K, Cramer MJ, Prinzen FW, Meine M
Heart Rhythm: 15 Feb 2021; epub ahead of print | PMID: 33601035
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Impact:
Abstract

Catheter ablation of ventricular tachycardia in ischemic cardiomyopathy: Impact of concomitant amiodarone therapy on short- and long-term clinical outcomes.

Di Biase L, Romero J, Du X, Mohanty S, ... Chen M, Natale A
Background
Substrate catheter ablation of scar-related ventricular tachycardia (VT) is a widely accepted therapeutic option for patients with ischemic cardiomyopathy (ICM).
Objective
The purpose of this study was to investigate whether concomitant amiodarone therapy affects procedural outcomes.
Methods
A total of 134 consecutive patients (89% male; age 66 ± 10 years) with ICM undergoing catheter ablation of VT were included in the study. Patients were sorted by amiodarone therapy before ablation. In all patients, a substrate-based catheter ablation (endocardial ± epicardial) in sinus rhythm abolishing all \"abnormal\" electrograms within the scar was performed. The endpoint of the procedure was VT noninducibility. After the ablation procedure, all antiarrhythmic medications were discontinued. All patients had an implantable cardioverter-defibrillator, and recurrences were analyzed through the device.
Results
In 84 patients (63%), the ablation was performed on amiodarone; the remaining 50 patients (37%) were off amiodarone. Patients had comparable baseline characteristics. Mean scar size area was 143.6 ± 44.9 cm2 on amiodarone vs 139.2 ± 36.8 cm2 off amiodarone (P = .56). More radiofrequency time was necessary to achieve noninducibility in the off-amiodarone group compared to the on-amiodarone group (68.1 ± 20.1 minutes vs 51.5 ± 19.7 minutes; P <.001). In addition, due to persistent VT inducibility, more patients in the off-amiodarone group required epicardial ablation than in the on-amiodarone group (13/50 [26%] vs 5/84 [6%], respectively; P <.001). During mean follow-up of 23.9 ± 11.6 months, recurrence of any ventricular arrhythmias off antiarrhythmic drugs was 44% (37/84) in the on-amiodarone group vs 22% (11/50) in the off-amiodarone group (P = .013).
Conclusion
Albeit, VT noninducibility after substrate CA for scar related VT was achieved faster, with less radiofrequency time and less need for epicardial ablation in patients taking amiodarone, these patients had significantly higher VT recurrence at long-term follow-up when this medication was discontinued.

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

Heart Rhythm: 12 Feb 2021; epub ahead of print
Di Biase L, Romero J, Du X, Mohanty S, ... Chen M, Natale A
Heart Rhythm: 12 Feb 2021; epub ahead of print | PMID: 33592323
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Impact:
Abstract

Racial disparities in the utilization and in-hospital outcomes of percutaneous left atrial appendage closure among patients with atrial fibrillation.

Vincent L, Grant J, Ebner B, Potchileev I, ... Colombo R, de Marchena E
Background
Select patients with atrial fibrillation and contraindication to anticoagulation may benefit from percutaneous left atrial appendage closure (pLAAC).
Objective
The purpose of this study was to evaluate racial disparities in the nationwide utilization and outcomes of pLAAC.
Methods
We identified 16,830 hospitalizations for pLAAC between 2015 and 2017 using the National Inpatient Sample. Baseline characteristics, in-hospital mortality, complications, length of stay, and discharge disposition were assessed between White and Black/African American (AA) populations.
Results
Black/AA patients represented 4.1% of nationwide pLAAC recipients and were younger, more likely to be female, and had greater prevalence of hypertension, heart failure, hyperlipidemia, obesity, chronic kidney disease, and prior stroke history (P <.001 for all). Black/AA patients had significantly increased length of stay and nonroutine discharge (P <.001 for both) but comparable in-hospital mortality to White patients. Black/AA patients suffered from greater postoperative stroke (0.7% vs 0.2%), acute kidney injury (4.5% vs 2.1%), bleeding requiring transfusion (4.5% vs 1.4%), and venous thromboembolism (0.7% vs 0.1%; P <.01 for all). After controlling for possible confounding factors, Black/AA race was independently associated with significantly increased odds of bleeding requiring blood transfusion, stroke, venous thromboembolism, and nonroutine discharge.
Conclusion
Among pLAAC recipients nationwide, Black/AA populations were underrepresented and had greater complication rates, length of stay, and discharge complexity. This study highlights the importance of addressing ongoing racial disparities in both utilization and outcomes of pLAAC.

Published by Elsevier Inc.

Heart Rhythm: 11 Feb 2021; epub ahead of print
Vincent L, Grant J, Ebner B, Potchileev I, ... Colombo R, de Marchena E
Heart Rhythm: 11 Feb 2021; epub ahead of print | PMID: 33588068
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Impact:
Abstract

Benefits of routine prophylactic femoral access during transvenous lead extraction.

Chung DU, Müller L, Ubben T, Yildirim Y, ... Pecha S, Hakmi S
Background
The number of patients requiring lead extraction has been increasing in recent years. Despite significant advances in operator experience and technique, unexpected complications may occur. Prophylactic placement of femoral sheaths allows for immediate endovascular access for emergency procedures and may shorten response time in the event of complications.
Objective
The purpose of this study was to assess the benefits of routine prophylactic femoral access in patients undergoing transvenous lead extraction (TLE) and to evaluate the methods, frequency, and efficacy of the emergency measures used in those patients.
Methods
We conducted a retrospective analysis of patients who underwent TLE from January 2012 to February 2019. The data were analyzed with regard to procedural complications and deployment of emergency measures via femoral access.
Results
Two hundred eighty-five patients (mean age 65.3 ± 15.5 years) were included in the study. Median lead dwell time was 84 months (interquartile range 58-144). Overall complication rate was 4.2% (n = 12), with 1.8% major complications (n = 5). Clinical success rate was 97.2%. Procedure-related mortality was 1.1% (n = 3). Femoral sheaths were actively engaged in 9.1% (n = 26) of cases. Deployment of snares was the most common intervention (n = 10), followed by prophylactic (n = 6) or emergency placement (n = 1) of occlusion balloons, temporary pacing (n = 3), venous angioplasty (n = 3), diagnostic venography (n = 3), and extracorporeal membrane oxygenation (n = 1). We did not observe any femoral vascular complications due to prophylactic sheath placement.
Conclusion
Routine prophylactic placement of femoral sheaths shortens response time and quickly establishes control in the event of various complications that may occur during TLE procedures.

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

Heart Rhythm: 08 Feb 2021; epub ahead of print
Chung DU, Müller L, Ubben T, Yildirim Y, ... Pecha S, Hakmi S
Heart Rhythm: 08 Feb 2021; epub ahead of print | PMID: 33577972
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Impact:
Abstract

Temperature monitoring and temperature-driven irrigated radiofrequency energy titration do not prevent thermally induced esophageal lesions in pulmonary vein isolation: A randomized study controlled by esophagoscopy before and after catheter ablation.

Meininghaus DG, Blembel K, Waniek C, Kruells-Muench J, ... Kleemann T, Geller JC
Background
Endoscopically detected esophageal lesions (EDELs) are common following pulmonary vein isolation (PVI) and may progress to atrioesophageal fistula (AEF).
Objective
The purpose of this study was to study (1) the benefit of luminal esophageal temperature (LET) monitoring and (2) the impact of esophagogastroduodenoscopy (EGD) in detecting EDEL and defining pre-existing lesions. The primary endpoint was the number of ablation-induced lesions.
Methods
Patients with atrial fibrillation were randomized to PVI with LET monitoring (LET[+]) or without LET monitoring (LET[-]). All patients underwent EGD before and after PVI. Ablation power at the left atrial (LA) posterior wall was limited to 25 W in all patients and was titrated to a minimum of 10 W guided by esophageal temperature in the LET[+] group.
Results
Eighty-six patients (age 67 ± 10 years; 57% male) were included (44 LET[+], 42 LET[-]). PVI was achieved in all, and additional linear LA lesions were done in 50%. Eight patients developed EDEL (6 LET[+], 2 LET[-]; P = NS). Whereas LET <41°C did not differentiate with regard to EDEL formation, temperature overshooting ≥42°C was associated with a higher risk for new EDEL. Two-thirds of patients showed incidental findings (esophagitis, gastric ulcer) on preprocedural EGD; 8 esophageal lesions were pre-existing. Four patients in the LET[+] group developed epistaxis following insertion of the probe.
Conclusion
Monitoring of LET does not prevent ablation-induced esophageal lesions. Patients without temperature surveillance were not at higher risk, but temperatures ≥42°C were associated with increased likelihood of mucosal lesions.

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

Heart Rhythm: 05 Feb 2021; epub ahead of print
Meininghaus DG, Blembel K, Waniek C, Kruells-Muench J, ... Kleemann T, Geller JC
Heart Rhythm: 05 Feb 2021; epub ahead of print | PMID: 33561587
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Impact:
Abstract

Blood biomarkers to detect new-onset atrial fibrillation and cardioembolism in ischemic stroke patients.

Harpaz D, Bajpai R, Ng GJL, Soljak M, ... Tok AIY, Seet RCS
Background
Accumulating data suggest blood biomarkers could inform stroke etiology.
Objective
The purpose of this study was to investigate the performance of multiple blood biomarkers in elucidating stroke etiology with a focus on new-onset atrial fibrillation (AF) and cardioembolism.
Methods
Between January and December 2017, information on clinical and laboratory parameters and stroke characteristics was prospectively collected from ischemic stroke patients recruited from the National University Hospital, Singapore. Multiple blood biomarkers (N-terminal pro-brain natriuretic peptide [NT-proBNP], d-dimer, S100β, neuron-specific enolase, vitamin D, cortisol, interleukin-6, insulin, uric acid, and albumin) were measured in plasma. These variables were compared with stroke etiology and the risk of new-onset AF and cardioembolism using multivariable regression methods.
Results
Of the 515 ischemic stroke patients (mean age 61 years; 71% men), 44 (8.5%) were diagnosed with new-onset AF, and 75 (14.5%) had cardioembolism. The combination of 2 laboratory parameters (total cholesterol ≤169 mg/dL; triglycerides ≤44.5 mg/dL) and 3 biomarkers (NT-proBNP ≥294 pg/mL; S100β ≥64 pg/mL; cortisol ≥471 nmol/l) identified patients with new-onset AF (negative predictive value [NPV] 90%; positive predictive value [PPV] 73%; area under curve [AUC] 85%). The combination of 2 laboratory parameters (total cholesterol ≤169 mg/dL; triglycerides ≤44.5 mg/dL) and 2 biomarkers (NT-proBNP ≥507 pg/mL; S100β ≥65 pg/mL) identified those with cardioembolism (NPV 86%; PPV 78%; AUC 87%). Adding clinical predictors did not improve the performance of these models.
Conclusion
Blood biomarkers could identify patients with increased likelihood of cardioembolism and direct the search for occult AF.

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

Heart Rhythm: 05 Feb 2021; epub ahead of print
Harpaz D, Bajpai R, Ng GJL, Soljak M, ... Tok AIY, Seet RCS
Heart Rhythm: 05 Feb 2021; epub ahead of print | PMID: 33561586
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Impact:
Abstract

Transcatheter embolic coils to treat peridevice leaks after left atrial appendage closure.

Musikantow DR, Shivamurthy P, Croft LB, Kawamura I, ... Goldman ME, Reddy VY
Background
Left atrial appendage closure (LAAC) has proven to be an effective alternative to long-term oral anticoagulation in the prevention of thromboembolic events in patients with atrial fibrillation. In a minority of patients, inadequate seal may result in persistent peridevice flow and inability of the appendage to fully thrombose, thereby representing a potential source for thromboembolism.
Objective
The purpose of this study was to study the use of endovascular coiling of the appendage to address persistent peridevice leak in patients undergoing LAAC with the Watchman device.
Methods
This is a retrospective single-center analysis involving patients who underwent placement of a LAAC device and returned for endovascular coiling to address persistent device leak between 2018 and 2020. Baseline characteristics, procedural outcomes, and follow-up echocardiograms were analyzed to demonstrate the feasibility and safety of this technique.
Results
Patients (N = 20) were identified with a mean leak size of 3.8 ± 1.3 mm (range 2.5-7 mm), all of whom had a non-thrombosed appendage. Acute procedural success was achieved in 95% of patients. Complete or significant reduction in flow beyond the LAAC device was achieved in 61% and 33% of patients, respectively. The 1 procedure-related adverse event was a pericardial effusion before coil deployment, requiring percutaneous drainage.
Conclusion
The clinical impact of residual peridevice leak post-Watchman implantation is a matter of continuing investigation. However, appendage coiling represents a new therapeutic tool to address this potential source for thromboembolism. Further studies should address the clinical impact of this technique, including the safety of discontinuing anticoagulation after successful coiling.

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

Heart Rhythm: 03 Feb 2021; epub ahead of print
Musikantow DR, Shivamurthy P, Croft LB, Kawamura I, ... Goldman ME, Reddy VY
Heart Rhythm: 03 Feb 2021; epub ahead of print | PMID: 33549807
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Impact:
Abstract

Right bundle branch block ventricular tachycardia in arrhythmogenic right ventricular cardiomyopathy more commonly originates from the right ventricle: Criteria for identifying chamber of origin.

Marchlinski DF, Tschabrunn CM, Zado ES, Santangeli P, Marchlinski FE
Background
Right bundle branch block (RBBB) ventricular tachycardia (VT) morphology is a criterion for left ventricular (LV) involvement in arrhythmogenic right ventricular cardiomyopathy (ARVC).
Objective
The purpose of this study was to determine the frequency and chamber of origin of RBBB VT in patients with ARVC and VT.
Methods
We studied 110 consecutive patients with VT who met the diagnostic International Task Force criteria for ARVC and underwent VT mapping/ablation. Patients with ≥1 RBBB VT were identified. Right ventricular (RV) origin of the RBBB VT was determined based on standard mapping criteria and elimination with ablation.
Results
Nineteen patients (17%) had 26 RBBB VTs. Eleven of these 19 patients (58%) had 16 RBBB VTs from the RV, and 9 patients (47%) had 10 RBBB VTs originating from the LV, with 1 patient demonstrating both. RBBB VT from RV most commonly (13/16 RBBB VTs) had an early precordial QRS transition (V2 or V3), with superiorly and typically leftward directed frontal plane axis, consistent with exit from dilated RV adjacent to inferior LV septum, whereas all 10 VTs from LV had RBBB morphology with positive R waves to V5 or V6 and rightward axis in 6 VTs characteristic of basal lateral origin.
Conclusion
In patients with ARVC and VT presenting for VT ablation, RBBB VT occurs in 17% of cases, with most RBBB VTs (62%) originating from the RV and not indicative of LV origin. Precordial R-wave transition and frontal plane axis can be used to identify the anticipated chamber of origin of RBBB VT.

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

Heart Rhythm: 30 Jan 2021; 18:163-171
Marchlinski DF, Tschabrunn CM, Zado ES, Santangeli P, Marchlinski FE
Heart Rhythm: 30 Jan 2021; 18:163-171 | PMID: 32889109
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Impact:
Abstract

Long QT syndrome type 1 and 2 patients respond differently to arrhythmic triggers: The TriQarr in vivo study.

Marstrand P, Almatlouh K, Kanters JK, Graff C, ... Bundgaard H, Theilade J
Background
In patients with long QT syndrome (LQTS), swimming and loud noises have been identified as genotype-specific arrhythmic triggers in LQTS type 1 (LQTS1) and LQTS type 2 (LQTS2), respectively.
Objective
The purpose of this study was to compare LQTS group responses to arrhythmic triggers.
Methods
LQTS1 and LQTS2 patients were included. Before and after beta-blocker intake, electrocardiograms were recorded as participants (1) were exposed to a loud noise of ∼100 dB; and (2) had their face immersed into cold water.
Results
Twenty-three patients (9 LQTS1, 14 LQTS2) participated. In response to noise, LQTS groups showed similarly increased heart rate, but LQTS2 patients had corrected QT interval (Fridericia formula) (QTcF) prolonged significantly more than LQTS1 patients (37 ± 8 ms vs 15 ± 6 ms; P = .02). After intake of beta-blocker, QTcF prolongation in LQTS2 patients was significantly blunted and similar to that of LQTS1 patients (P = .90). In response to simulated diving, LQTS groups experienced a heart rate drop of ∼28 bpm, which shortened QTcF similarly in both groups. After intake of beta-blockers, heart rate dropped to 28 ± 2 bpm in LQTS1 patients and 20 ± 3 bpm in LQTS2, resulting in a slower heart rate in LQTS1 compared with LQTS2 (P = .01). In response, QTcF shortened similarly in LQTS1 and LQTS2 patients (57 ± 9 ms vs 36 ± 7 ms; P = .10).
Conclusion
When exposed to noise, LQTS2 patients had QTc prolonged significantly more than did LQTS1 patients. Importantly, beta-blockers reduced noise-induced QTc prolongation in LQTS2 patients, thus demonstrating the protective effect of beta-blockers. In response to simulated diving, LQTS groups responded similarly, but a slower heart rate was observed in LQTS1 patients during simulated diving after beta-blocker intake.

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

Heart Rhythm: 30 Jan 2021; 18:241-249
Marstrand P, Almatlouh K, Kanters JK, Graff C, ... Bundgaard H, Theilade J
Heart Rhythm: 30 Jan 2021; 18:241-249 | PMID: 32882399
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Impact:
Abstract

Cardiac arrhythmias and sudden unexpected death in epilepsy: Results of long-term monitoring.

Serdyuk S, Davtyan K, Burd S, Drapkina O, ... Gusev E, Topchyan A
Background
Cardiac rhythm and conduction disorders are common in patients with epilepsy and are presumably one of the leading causes of sudden unexpected death. There are only a few published reports on ictal cardiac arrhythmias detected by continuous monitoring, and the majority had a small sample size.
Objective
The aim of this study was to evaluate the frequency and type of cardiac arrhythmias recorded by an implantable loop recorder in patients with drug-resistant epilepsy.
Methods
We implanted a subcutaneous loop recorder to 193 patients with drug-resistant epilepsy. Automatic triggers to initiate cardiac rhythm recording were cardiac pauses of >3 seconds and any episodes of bradycardia (≤45 beats/min) or tachycardia (≥150 beats/min). Patients/relatives were instructed to begin peri-ictal rhythm recording by using an external activator device. The follow-up duration was 36 months, with scheduled follow-up visits every 3 months.
Results
A total of 6494 electrocardiogram traces were recorded during the median follow-up of 36 months (interquartile range 3-36 months). Ictal heart rhythm and rate changes were detected in 143 patients (74%). The most common finding was ictal sinus tachycardia (66.8%). Sinus bradycardia was observed in 13 patients (6.7%). Three patients had clinically relevant cardiac pauses of >6 seconds, requiring permanent pacemaker implantation. Five patients (2.6%) died suddenly.
Conclusion
Ictal heart rhythm and rate changes occur in most of the patients with drug-resistant epilepsy. Clinically relevant cardiac events, related to ictal and postictal periods, are rare. No potentially malignant arrhythmias were detected in patients who died suddenly during the preceding follow-up period.

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

Heart Rhythm: 30 Jan 2021; 18:221-228
Serdyuk S, Davtyan K, Burd S, Drapkina O, ... Gusev E, Topchyan A
Heart Rhythm: 30 Jan 2021; 18:221-228 | PMID: 32911052
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Impact:
Abstract

Effects of 60-Hertz notch filtering on local abnormal ventricular activities.

Zhou X, Jiang Y, Sohinki D, Liu W, Po SS
Background
It is known that electrical signals can be affected by notch filtering.
Objective
We sought to investigate the effect of 60-Hz notch filtering on local abnormal ventricular activities (LAVA) in patients undergoing ventricular tachycardia ablation.
Methods
To ensure catheter stability, only patients undergoing ablation using Stereotaxis mapping catheters were enrolled. Catheter stability was judged by the display on the electroanatomic map and the morphology of the bipolar and unipolar electrograms of the ablation catheter. At sites recording stable LAVA, 60-Hz notch filtering was applied. The duration, amplitude, and morphology of LAVA were compared before and after filtering. The area under LAVA was used to analyze the amplitude of continuous LAVA.
Results
A total of 110 LAVA potentials recorded from 13 patients were analyzed. Notch filtering significantly affected the LAVA morphology and reduced their amplitude (the sum of the absolute value of the largest positive and negative voltages before filtering: 0.267 mV [0.191-0.395 mV]; after filtering: 0.172 mV [0.112-0.266 mV]; P < .001). At least 2 high-frequency components were introduced into the LAVA by filtering at 33 sites. The area under continuous LAVA was reduced by 28% from 24.64 cm2 (16.20-33.45 cm2) to 17.53 cm2 (10.52-23.82 cm2) (P < .001). The duration of continuous LAVA was reduced by 12% from 79.2 ms (55.0-93.0 ms) to 69.5 ms (53.0-88.5 ms) (P < .001).
Conclusion
Notch filtering can distort LAVA by reducing their amplitude, changing their morphology, and shortening their duration, leading to potential false positives and negatives. Mitigating the 60-Hz noise should focus on eliminating the source of noise, not applying notch filtering.

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

Heart Rhythm: 30 Jan 2021; 18:172-180
Zhou X, Jiang Y, Sohinki D, Liu W, Po SS
Heart Rhythm: 30 Jan 2021; 18:172-180 | PMID: 32911051
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Impact:
Abstract

Right bundle branch block-type wide QRS complex tachycardia with a reversed R/S complex in lead V: Development and validation of electrocardiographic differentiation criteria.

Kim M, Kwon CH, Lee JH, Hwang KW, ... Park HS, Nam GB
Background
Differentiation of supraventricular tachycardia (SVT) with a right bundle branch block (RBBB) pattern from ventricular tachycardia (VT) is difficult, particularly when the R/S ratio in lead V6 is below 1.0.
Objective
We sought to investigate the electrocardiographic criteria for distinguishing between these arrhythmias.
Methods
We investigated electrocardiographic parameters from 111 consecutive patients who had RBBB pattern wide QRS complex tachycardia with a reversed R/S ratio in lead V6 (72 VTs, 39 SVTs). Diagnostic criteria from the previous algorithms were compared with our new criterion, the RS/QRS ratio, which was defined as the ratio of the interval from the onset of the QRS complex to the nadir of the S wave, divided by the QRS width in lead V6. The RS/QRS ratio was further tested in a prospective population (31 fascicular VTs, 29 SVTs).
Results
The diagnostic accuracy of previous criteria (Brugada algorithm, Vereckei algorithm, and R-wave peak time criterion) was only modest. However, the RS/QRS ratio in lead V6 was significantly lower in SVT than in VT (0.36 ± 0.04 vs 0.50 ± 0.08; P < .001). A cutoff value of the RS/QRS ratio >0.41 differentiated VT from SVT with a high diagnostic accuracy (sensitivity 97.2%; specificity 89.7%). When tested in a prospective population with fascicular VT, the diagnostic accuracy of the criteria was maintained (sensitivity 90.3%; specificity 86.2%).
Conclusion
The RS/QRS ratio >0.41 in lead V6 is a simple and reliable index for distinguishing VT from SVT in RBBB pattern wide QRS complex tachycardia with a reversed R/S complex in lead V6. This criterion was particularly useful for the differential diagnosis of fascicular VT from RBBB pattern SVT.

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

Heart Rhythm: 30 Jan 2021; 18:181-188
Kim M, Kwon CH, Lee JH, Hwang KW, ... Park HS, Nam GB
Heart Rhythm: 30 Jan 2021; 18:181-188 | PMID: 32927100
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Impact:
Abstract

Lead-related superior vena cava syndrome: Management and outcomes.

Arora Y, Carrillo RG
Background
Superior vena cava (SVC) syndrome includes the clinical sequalae of facial and bilateral upper extremity edema, dizziness, and occasional syncope. Historically, most cases have been associated with malignancy and treatment is palliative. However, cardiac device leads have been identified as important nonmalignant causes of this syndrome. There are little data on the effectiveness of venoplasty and lead extraction in the management of these patients.
Objective
The objective of this study was to report the findings associated with the use of balloon angioplasty and lead extraction in the management of 17 patients with lead induced SVC syndrome.
Methods
Data collected from January 2003 to July 2019 identified 17 cases of SVC syndrome at our tertiary center. Their outcomes were compared to a control group of patients without SVC syndrome. A P value of <.05 was considered statistically significant.
Results
Of the 17 patients, 13 (76%) underwent transvenous lead extraction and venoplasty. Three patients (18%) were treated with venoplasty alone, and 1 patient (6%) underwent surgical SVC reconstruction. In 10 patients (59%), transvenous reimplantation was necessary. Symptom resolution was achieved in all 17 patients and confirmed at both 6 and 12 months\' follow-up. There was no significant difference in the rate of complications associated with transvenous lead extraction for SVC syndrome vs control.
Conclusion
In patients with SVC syndrome, venoplasty and lead extraction are safe and effective for resolution of symptoms and maintaining SVC patency.

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

Heart Rhythm: 30 Jan 2021; 18:207-214
Arora Y, Carrillo RG
Heart Rhythm: 30 Jan 2021; 18:207-214 | PMID: 32920177
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Impact:
Abstract

Calcium signaling consequences of RyR2 mutations associated with CPVT1 introduced via CRISPR/Cas9 gene editing in human-induced pluripotent stem cell-derived cardiomyocytes: Comparison of RyR2-R420Q, F2483I, and Q4201R.

Zhang XH, Wei H, Xia Y, Morad M
Background
Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) created from patients with catecholaminergic polymorphic ventricular tachycardia 1 (CPVT1) have been used to study CPVT1 arrhythmia.
Objective
The purpose of this study was to evaluate the Ca2+ signaling aberrancies and pharmacological sensitivities of 3 CRISPR/Cas9-introduced CPVT1 mutations located in different molecular domains of ryanodine receptor 2 (RyR2).
Methods
CRISPR/Cas9-engineered hiPSC-CMs carrying RyR2 mutations-R420Q, Q4201R, and F2483I-were voltage clamped, and their electrophysiology, pharmacology, and Ca2+ signaling phenotypes measured using total internal reflection fluorescence microscopy.
Results
R420Q and Q4201R mutant hiPSC-CMs exhibit irregular, long-lasting, spatially wandering Ca2+ sparks and aberrant Ca2+ releases similar to F2483I unlike the wild-type myocytes. Large sarcoplasmic reticulum (SR) Ca2+ leaks and smaller SR Ca2+ contents were detected in cells expressing Q4201R and F2483I, but not R420Q. Fractional Ca2+ release and calcium-induced calcium release gain were higher in Q4201R than in R420Q and F2483I hiPSC-CMs. JTV519 was equally effective in suppressing Ca2+ sparks, waves, and SR Ca2+ leaks in hiPSC-CMs derived from all 3 mutant lines. Flecainide and dantrolene similarly suppressed SR Ca2+ leaks, but were less effective in decreasing spark frequency and durations.
Conclusion
CRISPR/Cas9 gene editing of hiPSCs provides a novel approach in studying CPVT1-associated RyR2 mutations and suggests that Ca2+-signaling aberrancies and drug sensitivities may vary depending on the mutation site.

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

Heart Rhythm: 30 Jan 2021; 18:250-260
Zhang XH, Wei H, Xia Y, Morad M
Heart Rhythm: 30 Jan 2021; 18:250-260 | PMID: 32931925
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Impact:
Abstract

Effects of subcutaneous nerve stimulation with blindly inserted electrodes on ventricular rate control in a canine model of persistent atrial fibrillation.

Kusayama T, Wan J, Yuan Y, Liu X, ... Everett TH, Chen PS
Background
Subcutaneous nerve stimulation (ScNS) delivered directly to large subcutaneous nerves can be either antiarrhythmic or proarrhythmic, depending on the stimulus output.
Objective
The purpose of this study was to perform a prospective randomized study in a canine model of persistent AF to test the hypothesis that high-output ScNS using blindly inserted subcutaneous electrodes can reduce ventricular rate (VR) during persistent atrial fibrillation (AF) whereas low-output ScNS would have opposite effects.
Methods
We prospectively randomized 16 male and 15 female dogs with sustained AF (>48 hours) induced by rapid atrial pacing into 3 groups (sham, 0.25 mA, 3.5 mA) for 4 weeks of ScNS (10 Hz, alternating 20-seconds ON and 60-seconds OFF).
Results
ScNS at 3.5 mA, but not 0.25 mA or sham, significantly reduced VR and stellate ganglion nerve activity (SGNA), leading to improvement of left ventricular ejection fraction (LVEF). No differences were found between the 0.25-mA and sham groups. Histologic studies showed a significant reduction of bilateral atrial fibrosis in the 3.5-mA group compared with sham controls. Only 3.5-mA ScNS had significant fibrosis in bilateral stellate ganglions. The growth-associated protein 43 (GAP43) staining of stellate ganglions indicated the suppression of GAP43 protein expression in the 3.5-mA group. There were no significant differences of nerve sprouting among all groups. There was no interaction between sex and ScNS effects on reduction of VR and SGNA, LVEF improvement, or results of histologic studies.
Conclusion
We conclude that 3.5-mA ScNS with blindly inserted electrodes can improve VR control, reduce atrial fibrosis, and partially improve LVEF in a canine model of persistent AF.

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

Heart Rhythm: 30 Jan 2021; 18:261-270
Kusayama T, Wan J, Yuan Y, Liu X, ... Everett TH, Chen PS
Heart Rhythm: 30 Jan 2021; 18:261-270 | PMID: 32956842
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Impact:
Abstract

Differentiating hereditary arrhythmogenic right ventricular cardiomyopathy from cardiac sarcoidosis fulfilling 2010 ARVC Task Force Criteria.

Gasperetti A, Rossi VA, Chiodini A, Casella M, ... Duru F, Saguner AM
Background
The clinical presentation of cardiac sarcoidosis (CS) may resemble that of arrhythmogenic right ventricular cardiomyopathy (ARVC).
Objective
The purpose of this study was to identify clinical variables to better discriminate between patients with genetically determined ARVC and those with CS fulfilling definite 2010 ARVC Task Force Criteria (TFC).
Methods
In this multicenter study, 10 patients with CS fulfilling definite 2010 ARVC TFC were age and gender matched with 10 genetically proven ARVC patients. A cardiac 18F-fluorodeoxyglucose positron emission tomographic (18F-FDG PET) scan was required for patients to be included in the study.
Results
The 2010 ARVC TFC did not reliably differentiate between the 2 diseases. CS patients presented with longer PR intervals, advanced atrioventricular block (AVB), and longer QRS duration (P <.001 and P = .009, respectively), whereas T-wave inversions (TWIs) in the peripheral leads were more common in ARVC patients (P = .009). CS patients presented with more extensive left ventricular involvement and lower left ventricular ejection fraction (LVEF), whereas ARVC patients had a larger right ventricular outflow tract (RVOT) (P = .044). PET scan positivity was only present in CS patients (90% vs 0%).
Conclusion
The 2010 ARVC TFC do not reliably differentiate between CS patients fulfilling 2010 ARVC TFC and those with hereditary ARVC. Prolonged PR interval, advanced AVB, longer QRS duration, right ventricular apical involvement, reduced LVEF, and positive 18F-FDG PET scan should raise the suspicion of CS, whereas larger RVOT dimensions, subtricuspid involvement and peripheral TWI favor a diagnosis of hereditary ARVC.

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

Heart Rhythm: 30 Jan 2021; 18:231-238
Gasperetti A, Rossi VA, Chiodini A, Casella M, ... Duru F, Saguner AM
Heart Rhythm: 30 Jan 2021; 18:231-238 | PMID: 32976989
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Impact:
Abstract

Mapping and ablation of clinical spontaneous perimitral atrial tachycardias using an ultra-high-resolution mapping system.

Miyazaki S, Hasegawa K, Yamao K, Ishikawa E, ... Iesaka Y, Tada H
Background
Perimitral atrial tachycardias (PMATs) are common atrial tachycardias (ATs), yet their mechanisms vary.
Objective
The purpose of this study was to characterize clinical spontaneous PMATs using an ultra-high-resolution (UHR) mapping system.
Methods
The study included 32 consecutive PMATs in 31 patients who had undergone AT mapping/ablation using a UHR mapping system.
Results
Six, 10, 11, and 5 PMATs occurred in cardiac intervention-naïve (group A), post-lateral/posterior mitral isthmus linear ablation (group B), post-atrial fibrillation ablation without mitral isthmus linear ablation (group C), and post-cardiac surgery (group D) patients, respectively. Group A patients tended to be older, more likely were female, and had sinus node or atrioventricular conduction disturbances more frequently. A 12-lead synchronous isoelectric interval was observed in 15 PMATs (46.9%). Coronary sinus activation was proximal to distal or distal to proximal except in 3 PMATs with straight patterns due to epicardial gaps. Left atrial anterior/septal wall (LAASW) low-voltage areas were smallest in group B. Slow conduction areas (SCAs) were identified in 26 PMATs (81.2%) and were located on the LAASW in all group A and group D patients. Conduction velocity in the SCAs was slowest in group B. In group B, all PMATs were terminated by single applications, and the gaps were located epicardially in 5 of 10 (50%). Anterior (n = 23) or lateral/posterior (n = 9) mitral isthmus linear block was successfully created without any complications in all. Twenty-five concomitant ATs among 18 patients (58.1%) also were eliminated. During a median of 20.0 (11.0-40.0) months of follow-up, 28 patients (90.3%) were free from any atrial tachyarrhythmias.
Conclusion
An UHR mapping-guided approach with identification of the individual tachycardia mechanism should be the preferred strategy given the distinct and complex arrhythmia mechanisms.

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

Heart Rhythm: 30 Jan 2021; 18:189-198
Miyazaki S, Hasegawa K, Yamao K, Ishikawa E, ... Iesaka Y, Tada H
Heart Rhythm: 30 Jan 2021; 18:189-198 | PMID: 33007441
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Abstract

Anticoagulation for stroke prevention in patients with hypertrophic cardiomyopathy and atrial fibrillation: A review.

Nasser MF, Gandhi S, Siegel RJ, Rader F
Atrial fibrillation is the most common arrhythmia in patients with hypertrophic cardiomyopathy, with a prevalence of 23% and incidence of 3.1%. The risk of thromboembolism is high in patients with hypertrophic cardiomyopathy regardless of CHADS2-VASc score. This review includes 5 observational studies that focused on prevention of thromboembolism in patients with hypertrophic cardiomyopathy and atrial fibrillation. The studies evaluated and compared outcomes between patients receiving either warfarin or direct oral anticoagulants. Data showed that direct oral anticoagulants are effective and safe in this patient population and may have a benefit over warfarin for thromboprophylaxis in patients with hypertrophic cardiomyopathy and atrial fibrillation. Because of the high risk of thromboembolism, lifelong anticoagulation with warfarin is recommended to prevent thromboembolism in patients with atrial fibrillation and hypertrophic cardiomyopathy. The available observational data reviewed suggest that direct oral anticoagulants may be safe and effective in this patient population. However, adequately powered randomized controlled trials are needed to confirm their efficacy and safety.

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

Heart Rhythm: 30 Jan 2021; 18:297-302
Nasser MF, Gandhi S, Siegel RJ, Rader F
Heart Rhythm: 30 Jan 2021; 18:297-302 | PMID: 33022393
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Abstract

Critical repolarization gradients determine the induction of reentry-based torsades de pointes arrhythmia in models of long QT syndrome.

Rivaud MR, Bayer JD, Cluitmans M, van der Waal J, ... Meijborg VMF, Coronel R
Background
Torsades de pointes arrhythmia is a potentially lethal polymorphic ventricular tachyarrhythmia (pVT) in the setting of long QT syndrome. Arrhythmia susceptibility is influenced by risk factors modifying repolarization.
Objective
The purpose of this article was to characterize repolarization duration and heterogeneity in relation to pVT inducibility and maintenance.
Methods
Sotalol was infused regionally or globally in isolated Langendorff blood-perfused pig hearts (N = 7) to create repolarization time (RT) heterogeneities. Programmed stimulation and epicardial activation and repolarization mapping were performed. The role of RT (heterogeneities) was studied in more detail using a computer model of the human heart.
Results
pVTs (n = 11) were inducible at a critical combination of RT and RT heterogeneities. The pVT cycle lengths were similar in the short and long RT regions. Short-lasting pVTs were maintained by focal activity while longer-lasting pVTs by reentry wandering along the interface between the 2 regions. Local restitution curves from the long and short RT regions crossed. This was associated with T-wave inversion at coupling intervals at either side of the crossing point. These experimental observations were confirmed by the computer simulations.
Conclusion
pVTs are inducible within a critical range of RT and RT heterogeneities and are maintained by reentry wandering along the repolarization gradient. Double potentials localize at the core of the reentrant circuit and reflect phase singularities. RT gradient and T waves invert with short-coupled premature beats in the long RT region as a result of the crossing of the restitution curves allowing reentry initiation.

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

Heart Rhythm: 30 Jan 2021; 18:278-287
Rivaud MR, Bayer JD, Cluitmans M, van der Waal J, ... Meijborg VMF, Coronel R
Heart Rhythm: 30 Jan 2021; 18:278-287 | PMID: 33031961
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