Journal: Heart Rhythm

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Abstract

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

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

Copyright © 2021. Published by Elsevier Inc.

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

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

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

Copyright © 2021. Published by Elsevier Inc.

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

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

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

Copyright © 2021. Published by Elsevier Inc.

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

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

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

Copyright © 2021. Published by Elsevier Inc.

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

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

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

Copyright © 2021. Published by Elsevier Inc.

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

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

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

Copyright © 2021. Published by Elsevier Inc.

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

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

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

Copyright © 2021. Published by Elsevier Inc.

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

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

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

Copyright © 2021. Published by Elsevier Inc.

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

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

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

Copyright © 2021. Published by Elsevier Inc.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Copyright © 2021. Published by Elsevier Inc.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Aorticorenal ganglion as a novel target for renal neuromodulation.

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

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

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

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

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

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

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

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

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

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

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

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

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

Copyright © 2021. Published by Elsevier Inc.

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

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

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

Copyright © 2021. Published by Elsevier Inc.

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

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

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

Copyright © 2021. Published by Elsevier Inc.

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

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

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

Copyright © 2021. Published by Elsevier Inc.

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

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

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

Published by Elsevier Inc.

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

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

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

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

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

Interpreting Device Diagnostics for Lead Failure.

Swerdlow CD, Ploux S, Poole JE, Nair SG, Himes A, Ellenbogen KA
Implantable cardioverter-defibrillators (ICDs) incorporate automated, lead-monitoring alerts (alerts) and other diagnostics to detect defibrillation lead failure (LF) and minimize its adverse clinical consequences. Partial conductor fractures cause oversensing, but pacing or high-voltage alerts for high impedance detect only complete conductor fracture. In both pacing and high-voltage insulation breaches, low-impedance alerts require complete breach with metal-to-metal contact. Oversensing alerts for pace-sense LF also require complete breach, but not metal-to metal contact. Electrograms (EGMs) from leads with confirmed fractures have characteristics findings. In insulation breach however, oversensed EGMs reflect characteristics of the source signal. Oversensing alerts that operate on the sensing channel analyze R-R intervals for two patterns typical of LF but uncommon in other conditions, a rapidly-increasing count of \"non-physiologic,\" short intervals and rapid \"nonsustained tachycardias.\" These alerts are sensitive but nonspecific. Alerts that compare sensing and shock channels define oversensing as sensed events that do not correlate temporally with EGMs on the shock channel. Their performance depends on implementation. Specific advantages and limitations are reviewed. Most ICD measure impedance using subthreshold pulses. Patterns in impedance trends provide diagnostic information, whether or not an alert is triggered. Gradual increases in impedance do not indicate structural LF, but they may cause failed defibrillation if shock impedance is high enough. Since impedance-threshold alerts are insensitive, normal impedance trends never exclude LF; but an abrupt increase that triggers an alert almost always indicates a header-connection issue or LF. Methods for discriminating connection issues from LF are reviewed.

Copyright © 2021. Published by Elsevier Inc.

Heart Rhythm: 27 Sep 2021; epub ahead of print
Swerdlow CD, Ploux S, Poole JE, Nair SG, Himes A, Ellenbogen KA
Heart Rhythm: 27 Sep 2021; epub ahead of print | PMID: 34597770
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Impact:
Abstract

Novel aggregated multiposition noncontact mapping of atrial tachycardia in humans: From computational modeling to clinical validation.

Shi R, Zaman JAB, Chen Z, Shi X, ... Grace A, Wong T
Background
A novel aggregated multiposition noncontact mapping (AMP-NCM) algorithm is proposed to diagnose cardiac arrhythmias.
Objective
The purpose of this study was to computationally determine an accuracy threshold and to compare the accuracy and clinical utility of AMP-NCM to gold standard contact mapping.
Methods
In a cellular automata model, the number of catheter positions and chamber coverage were varied to establish accuracy requirements for clinically relevant AMP-NCM. This guided the clinical study protocol. In a prospective cohort of patients with atrial tachycardia (AT), noncontact mapping (NCM) recordings from a single position (SP) and multiple positions were compared to contact mapping with a high-density multipolar catheter using morphology and timing differences of reconstructed signals. Identification of AT mechanisms and ablation targets using both AMP-NCM and contact mapping were randomly evaluated by 5 blinded reviewers.
Results
AMP-NCM accuracy was asymptotic at 60 catheter positions in computational modeling. Twenty patients (age 65 ± 12 years; 19 male) with 26 ATs (5 focal, 21 reentrant) were studied. Morphologic correlation of signals derived from AMP-NCM was significantly better than those from SP-NCM compared to contact signals (median 0.93 vs 0.76; P <.001). AMP-NCM generated maps more rapidly than contact mapping (3 ± 1 minutes vs 13 ± 6 minutes; P <.001) and correctly diagnosed AT mechanisms in 25 of 26 maps (96%). Overall, 80% of arrhythmia mechanisms were correctly identified using AMP-NCM by blinded reviewers.
Conclusion
Once 60 catheter positions were achieved, AMP-NCM successfully diagnosed mechanisms of AT and identified treatment sites equal to gold standard contact mapping in 3 minutes of procedural time.

Copyright © 2021. Published by Elsevier Inc.

Heart Rhythm: 25 Sep 2021; epub ahead of print
Shi R, Zaman JAB, Chen Z, Shi X, ... Grace A, Wong T
Heart Rhythm: 25 Sep 2021; epub ahead of print | PMID: 34583060
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Impact:
Abstract

Successful continuous positive airway pressure treatment reduces skin sympathetic nerve activity in patients with obstructive sleep apnea.

Meng G, He W, Wong J, Li X, ... Chen PS, Tang Y
Background
Obstructive sleep apnea (OSA) is associated with cardiovascular diseases and increased sympathetic tone. We previously demonstrated that patients with OSA have increased skin sympathetic nerve activity (SKNA).
Objective
The purpose of this study was to test the hypothesis that continuous positive airway pressure (CPAP) treatment reduces SKNA.
Methods
The electrocardiogram, SKNA, and polysomnographic recording were recorded simultaneously in 9 patients with OSA. After baseline recording, CPAP titration was performed and the pressure was adjusted gradually for the optimal treatment, defined by reducing the apnea-hypopnea index (AHI) to ≤5/h. Otherwise the treatment was considered suboptimal (AHI > 5/h). Fast Fourier transform analyses were performed to investigate the frequency spectrum of SKNA.
Results
There were very low frequency (VLF), low frequency (LF), and high frequency (HF) oscillations in SKNA. The HF oscillation matched the frequency of respiration. OSA episodes were more frequently associated with the VLF and LF than with the HF oscillations of SKNA. Compared with baseline, CPAP significantly decreased the arousal index and AHI and increased the minimal and average O2 saturation. Optimal treatment significantly increased the dominant frequency and reduced the heart rate, average SKNA (aSKNA), SKNA burst duration, and total burst area. The dominant frequency negatively correlated with aSKNA.
Conclusion
VLF, LF, and HF oscillations are observed in human SKNA recordings. Among them, VLF and LF oscillations are associated with OSA while HF oscillations are associated with normal breathing. CPAP therapy reduces aSKNA and shifts the frequency of SKNA oscillation from VLF or LF to HF.

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

Heart Rhythm: 22 Sep 2021; epub ahead of print
Meng G, He W, Wong J, Li X, ... Chen PS, Tang Y
Heart Rhythm: 22 Sep 2021; epub ahead of print | PMID: 34562644
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Impact:
Abstract

Right predominant electrical remodeling in a pure model of pulmonary hypertension promotes reentrant arrhythmias.

Strauss B, Bisserier M, Obus E, Katz MG, ... Sassi Y, Akar FG
Background
Electrophysiological (EP) properties have been studied mainly in the monocrotaline (MCT) model of pulmonary arterial hypertension (PAH). Findings are confounded by major extra-pulmonary toxicities which preclude the ability to draw definitive conclusions regarding the role of PAH per-se in EP remodeling.
Objective
To investigate the EP substrate and arrhythmic vulnerability of a new model of PAH that avoids extra-cardiopulmonary toxicities.
Methods
Sprague-Dawley rats underwent left pneumonectomy (Pn) followed by injection of the VEGF inhibitor Sugen-5416 (Su/Pn). 5-wks later, cardiac-MRI was performed in-vivo, optical AP mapping ex-vivo and molecular analyses in-vitro.
Results
Su/Pn rats exhibited RV hypertrophy and were highly prone to pacing-induced VT/VF. Underlying this susceptibility was disproportionate RV-sided prolongation of AP duration, which promoted formation of right-sided AP alternans at physiological rates. While propagation was impaired at all rates in Su/Pn, the extent of conduction slowing was most severe immediately prior to emergence of inter-ventricular lines of block and onset of VT/VF. Measurement of the cardiac wavelength revealed a decrease in Su/Pn relative to CTRL. Nav1.5 and total-Cx43 expression were not altered while Cx43 phosphorylation was decreased in PAH. Col1a1 and Col3a1 transcripts were upregulated coinciding with myocardial fibrosis. Once generated, VT/VF was sustained by multiple reentrant circuits with lower frequency of RV activation due to wavebreak formation.
Conclusion
In this pure model of PAH, we document RV-predominant remodeling that promotes multi-wavelet reentry underlying VT. The Su/Pn model represents a severe form of PAH that allows the study of EP properties without the confounding influence of extra-pulmonary toxicity.

Copyright © 2021. Published by Elsevier Inc.

Heart Rhythm: 22 Sep 2021; epub ahead of print
Strauss B, Bisserier M, Obus E, Katz MG, ... Sassi Y, Akar FG
Heart Rhythm: 22 Sep 2021; epub ahead of print | PMID: 34563688
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Impact:
Abstract

Role of chronic continuous intravenous lidocaine in the clinical management of patients with malignant type 3 long QT syndrome.

Bains S, Lador A, Neves R, Bos JM, ... Cannon BC, Ackerman MJ
Background
Type 3 long QT syndrome (LQT3) is caused by pathogenic, gain-of-function variants in SCN5A leading to a prolonged action potential, ventricular ectopy, and torsades de pointes. Treatment options include pharmacotherapy, cardiac denervation, and/or device therapy. Rarely, patients with malignant LQT3 require cardiac transplantation.
Objective
The purpose of this study was to evaluate the role of chronic continuous intravenous (IV) lidocaine as a therapeutic option for select patients with LQT3 refractory to standard therapy.
Methods
We performed a retrospective review of patients evaluated and treated at Mayo Clinic and identified 4 of 161 patients with LQT3 (2.5%) who were refractory to standard therapies and therefore treated with IV lidocaine.
Results
There were 4 patients (2 female [50%]). The median age at first IV lidocaine infusion was 2 months (interquartile range 1.5-4.8 months), and the median cumulative duration on IV lidocaine was 11.5 months (interquartile range 8.7-17.8 months). The main indication for IV lidocaine in all patients was persistent ventricular arrhythmias. Before IV lidocaine, all patients received an implantable cardioverter-defibrillator, and while on intermittent IV lidocaine, all patients underwent bilateral cardiac sympathetic denervation. Additionally, 2 (50%) patients had cardiac ablation for premature ventricular complexes. In all patients, lidocaine infusion resulted in a significant reduction of LQT3-triggered cardiac events. The main side effects of IV lidocaine observed were dizziness (n = 2, 50%) and seizures (n = 2, 50%). During follow-up, 3 of 4 (75%) patients underwent orthotopic cardiac transplantation. The remaining patient continues to receive IV lidocaine bolus for rescue as needed.
Conclusion
For patients with LQT3 who are refractory to standard treatment, chronic IV lidocaine infusion can be used as a potential \"bridge to transplant.\"

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

Heart Rhythm: 15 Sep 2021; epub ahead of print
Bains S, Lador A, Neves R, Bos JM, ... Cannon BC, Ackerman MJ
Heart Rhythm: 15 Sep 2021; epub ahead of print | PMID: 34537410
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Impact:
Abstract

Inhibitory G protein-mediated modulation of slow delayed rectifier potassium channels contributes to increased susceptibility to arrhythmogenesis in aging heart.

Zou S, Qiu S, Su S, Zhang J, ... Shi C, Xu Y
Background
Slow delayed rectifier potassium current (IKs) is an important component of repolarization reserve during sympathetic nerve excitement. However, little is known about age-related functional changes of IKs and its involvement in age-dependent arrhythmogenesis.
Objective
To investigate age-related alteration of the IKs response to β-adrenergic receptor (βAR) activation.
Methods
Dunkin-Hartley guinea pigs were used. Whole-cell patch-clamp recording was used to record K+ currents. Optical mapping of membrane potential was performed in ex vivo heart.
Results
There was no difference in IKs density in ventricular cardiomyocytes between young and old guinea pigs. However, in contrast to IKs potentiation in young hearts, isoproterenol (ISO) evoked an acute inhibition on IKs in a concentration-dependent manner in old guinea pig hearts. The β2AR antagonist, but not β1AR antagonist, reversed the inhibitory response. Preincubation of cardiomyocytes with the inhibitory G protein (Gi) inhibitor pertussis toxin (PTX) also reversed the inhibitory response. In HEK293 cells co-transfected with cloned IKs channel and β2AR, ISO enhanced the current but reduced it when cells were co-transfected with Gi2, and PTX restored the ISO-induced excitatory response. Moreover, in aging cardiomyocytes, Gβγ inhibitor gallein, PLC inhibitor U73122, or protein kinase C inhibitor Bis-1 prevented the reduction of IKs by ISO. Furthermore, cardiac-specific Gi2 overexpression in young guinea pigs predisposed the heart to ventricular tachyarrhythmias. PTX pretreatment protected the hearts from ventricular arrhythmias.
Conclusion
βAR activation acutely induces an inhibitory IKs response in aging guinea pig hearts through β2AR-Gi signaling, which contributes to increased susceptibility to arrhythmogenesis in aging hearts.

Copyright © 2021. Published by Elsevier Inc.

Heart Rhythm: 14 Sep 2021; epub ahead of print
Zou S, Qiu S, Su S, Zhang J, ... Shi C, Xu Y
Heart Rhythm: 14 Sep 2021; epub ahead of print | PMID: 34536591
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Impact:
Abstract

Ventricular arrhythmias in athletes: Role of a comprehensive diagnostic workup.

Dello Russo A, Compagnucci P, Casella M, Gasperetti A, ... Zeppilli P, Tondo C
Background
Ventricular arrhythmias (VAs) represent a critical issue with regard to sports eligibility assessment in athletes. The ideal diagnostic evaluation of competitive and leisure-time athletes with complex VAs has not been clearly defined.
Objective
The purpose of this study was to assess the clinical implications of invasive electrophysiological assessments and endomyocardial biopsy (EMB) among athletes with VAs.
Methods
We evaluated 227 consecutive athletes who presented to our institutions after being disqualified from participating in sports because of VAs. After noninvasive tests, electrophysiological study (EPS), electroanatomic mapping (EAM), and EAM- or cardiac magnetic resonance imaging-guided EMB was performed, following a prespecified protocol. Sports eligibility status was redefined at 6-month follow-up.
Results
From our sample, 188 athletes (82.8%) underwent EAM and EPS, and 42 (15.2%) underwent EMB. A diagnosis of heart disease could be formulated in 30% of the study population (67/227; 95% confidence interval [CI] 0.24-0.36) after noninvasive tests; in 37% (83/227; 95% CI 31%-43%) after EPS and EAM; and in 45% (102/227; 95% CI 39%-51%) after EMB. In the subset of athletes undergoing EMB, invasive diagnostic workup allowed diagnostic reclassification of half of the athletes (n = 21 [50%]). Reclassification was particularly common among subjects without definitive findings after noninvasive evaluation (n = 23; 87% reclassified). History of syncope, abnormal echocardiogram, presence of late gadolinium enhancement, and abnormal EAM were linked to sports ineligibility at 6-month follow-up.
Conclusion
A comprehensive invasive workup provided additional diagnostic elements and could improve the sports eligibility assessment of athletes presenting with VAs. The extensive invasive evaluation presented could be especially helpful when noninvasive tests show unclear findings.

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

Heart Rhythm: 14 Sep 2021; epub ahead of print
Dello Russo A, Compagnucci P, Casella M, Gasperetti A, ... Zeppilli P, Tondo C
Heart Rhythm: 14 Sep 2021; epub ahead of print | PMID: 34536590
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Impact:
Abstract

Effect of electrode size and spacing on electrograms: Optimal electrode configuration for near-field electrogram characterization.

Takigawa M, Kitamura T, Basu S, Bartal M, ... Hocini M, Jaïs P
Background
Detailed effects of electrode size on electrograms (EGMs) have not been systematically examined.
Objectives
We aimed to elucidate the effect of electrode size on EGMs and investigate an optimal configuration of electrode size and interelectrode spacing for gap detection and far-field reduction.
Methods
This study included 8 sheep in which probes with different electrode size and interelectrode spacing were epicardially placed on healthy, fatty, and lesion tissues for measurements. In study 1, EGMs were compared between 3 electrode sizes (0.1 mm/0.2 mm/0.5 mm) with 3 mm spacing. In study 2, gap to lesion voltage ratio and healthy to fat tissue voltage ratio were evaluated, as indices of capability in gap detection and far-field reduction, in different electrode sizes (0.1 mm/0.2 mm/0.5 mm) and interelectrode spacing (0.1 mm/0.2 mm/0.3 mm/0.5 mm/3 mm) and the optimal electrode size and interelectrode spacing were determined. In study 3, bipolar EGMs in atrial fibrillation (AF) were compared between PentaRay and the optimal probe determined in study 2.
Results
Study 1 demonstrated that unipolar voltage and the duration of EGMs increased as the electrode size increased in any tissue (P < .001). Bipolar EGMs had the same tendency in healthy/fatty tissues, but not in lesions. Study 2 showed that significantly higher gap to lesion volume ratio and healthy to fat tissue voltage ratio were provided by a smaller electrode (0.2 mm or 0.3 mm electrode) and smaller spacing (0.1 mm spacing), but 0.3 mm electrode/0.1 mm spacing provided a larger bipolar voltage (P < .05). Study 3 demonstrated that 0.3 mm electrode/0.1 mm spacing provided less deflection with more discrete EGMs (P < .0001) with longer and more reproducible AF cycle length (P < .0001) compared to PentaRay.
Conclusion
Electrode size affects both unipolar and bipolar EGMs. Catheters with microelectrodes and very small interelectrode spacing may be superior in gap detection and far-field reduction. Importantly, this electrode configuration could dramatically reduce artifactual complex fractionated atrial electrograms and may open a new era for AF mapping.

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

Heart Rhythm: 13 Sep 2021; epub ahead of print
Takigawa M, Kitamura T, Basu S, Bartal M, ... Hocini M, Jaïs P
Heart Rhythm: 13 Sep 2021; epub ahead of print | PMID: 34534699
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Impact:
Abstract

Time to diagnosis of acute complications after cardiovascular implantable electronic device insertion and optimal timing of discharge within the first 24 hours.

Wadhwani L, Occhipinti K, Selim A, Manmadhan A, ... Chinitz LA, Aizer A
Background
More than 3 million cardiovascular implantable electronic devices (CIEDs) are implanted annually. There are minimal data regarding the timing of diagnosis of acute complications after implantation. It remains unclear whether patients can be safely discharged less than 24 hours postimplantation.
Objective
The purpose of this study was to determine the precise timing of acute complication diagnosis after CIED implantation and optimal timing for same-day discharge.
Methods
A retrospective cohort analysis of adults 18 years or older who underwent CIED implantation at a large urban quaternary care medical center between June 1, 2015, and March 30, 2020, was performed. Standard of care included overnight observation and chest radiography 6 and 24 hours postprocedure. Medical records were reviewed for the timing of diagnosis of acute complications. Acute complications included pneumothorax, hemothorax, pericardial effusion, lead dislodgment, and implant site hematoma requiring surgical intervention.
Results
A total of 2421 patients underwent implantation. Pericardial effusion or cardiac tamponade was diagnosed in 13 patients (0.53%), pneumothorax or hemothorax in 19 patients (0.78%), lead dislodgment in 11 patients (0.45%), and hematomas requiring surgical intervention in 5 patients (0.2%). Of the 48 acute complications, 43 (90%) occurred either within 6 hours or more than 24 hours after the procedure. Only 3 acute complications identified between 6 and 24 hours required intervention during the index hospitalization (0.12% of all cases).
Conclusion
Most acute complications are diagnosed either within the first 6 hours or more than 24 hours after implantation. With rare exception, patients can be considered for discharge after 6 hours of appropriate monitoring.

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

Heart Rhythm: 09 Sep 2021; epub ahead of print
Wadhwani L, Occhipinti K, Selim A, Manmadhan A, ... Chinitz LA, Aizer A
Heart Rhythm: 09 Sep 2021; epub ahead of print | PMID: 34517119
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Impact:
Abstract

Sleep-disordered breathing is independently associated with reduced atrial connexin 43 expression.

Hegner P, Lebek S, Tafelmeier M, Camboni D, ... Arzt M, Wagner S
Background
Patients with atrial fibrillation (AF) exhibit decreased atrial expression of connexin (Cx), which has been causally linked to a proarrhythmogenic substrate. Interestingly, patients with sleep-disordered breathing (SDB) are at increased risk of AF, but the mechanisms remain unclear.
Objective
We tested the hypothesis that patients with SDB have reduced atrial Cx expression independent of important comorbidities.
Methods
We analyzed right atrial appendage biopsies from 77 patients undergoing coronary artery bypass grafting. Patients were tested for SDB by polygraphy before surgery. Expression of Cx40 and Cx43 messenger RNA was quantified using real-time quantitative polymerase chain reaction and Western blot (Cx43). Structural atrial remodeling was investigated histologically and by quantitative polymerase chain reaction. Postoperative AF was assessed by 12-lead electrocardiography.
Results
Patients were stratified according to apnea-hypopnea index (SDB if apnea-hypopnea index ≥15 per hour, n = 32 vs n = 45). Patients with SDB had significantly lower atrial Cx43 expression, which was negatively correlated with apnea-hypopnea index and oxygen desaturation index. No significant increase in atrial fibrosis or expression of hypertrophy and inflammatory markers was observed. Interestingly, SDB remained the strongest independent predictor of decreased atrial Cx43 expression in a multivariate logistic regression model including age, sex, diabetes, and heart failure with reduced ejection fraction (odds ratio 7.58; 95% confidence interval 1.891-30.375; P = .004). Moreover, reduced atrial Cx43 expression was strongly associated with the occurrence of postoperative AF (odds ratio 15.749; 95% confidence interval 1.072-231.472; P = .044).
Conclusion
Patients with SDB exhibited decreased atrial Cx43 expression, which correlated with the severity of SDB. This correlation was independent of several concomitant diseases and may be linked to an increased risk of AF after cardiac surgery.

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

Heart Rhythm: 09 Sep 2021; epub ahead of print
Hegner P, Lebek S, Tafelmeier M, Camboni D, ... Arzt M, Wagner S
Heart Rhythm: 09 Sep 2021; epub ahead of print | PMID: 34517118
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Impact:
Abstract

Role of subcutaneous implantable loop recorder for the diagnosis of arrhythmias in Brugada syndrome: A United Kingdom single-center experience.

Scrocco C, Ben-Haim Y, Devine B, Tome-Esteban M, ... Macfarlane PW, Behr ER
Background
Experience with implantable loop recorders (ILRs) in Brugada syndrome (BrS) is limited.
Objective
The purpose of this study was to evaluate the indications and yield of ILR monitoring in a single-center BrS registry.
Methods
Demographic, clinical and follow-up data of BrS patients with ILR were collected.
Results
Of 415 BrS patients recruited consecutively, 50 (12%) received an ILR (58% male). Mean age at ILR implantation was 44 ± 15 years. Thirty-one (62%) had experienced syncopal or presyncopal episodes, and 23 (46%) had palpitations. During median follow-up of 28 months (range 1-68), actionable events were detected in 11 subjects (22%); 7 had recurrences of syncope/presyncope, with 4 showing defects in sinus node function or atrioventricular conduction. New supraventricular tachyarrhythmias were recorded in 6 subjects; a run of fast nonsustained ventricular tachycardia was detected in 1 patient. Patients implanted with an ILR were less likely to show a spontaneous type 1 pattern or depolarization electrocardiographic (ECG) abnormalities compared to those receiving a primary prevention implantable-cardioverter defibrillator. Age at implantation, gender, Shanghai score, and ECG parameters did not differ between subjects with and those without actionable events. ILR-related complications occurred in 3 cases (6%).
Conclusion
In a large cohort of BrS patients, continuous ILR monitoring yielded a diagnosis of tachy- or bradyarrhythmic episodes in 22% of cases. Recurrences of syncope were associated with bradyarrhythmic events. Use of ILR can be helpful in guiding the management of low-/intermediate-risk BrS patients and ascertaining the cause of unexplained syncope.

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

Heart Rhythm: 02 Sep 2021; epub ahead of print
Scrocco C, Ben-Haim Y, Devine B, Tome-Esteban M, ... Macfarlane PW, Behr ER
Heart Rhythm: 02 Sep 2021; epub ahead of print | PMID: 34487893
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Impact:
Abstract

Clinical outcomes of left bundle branch area pacing compared to right ventricular pacing: Results from the Geisinger-Rush Conduction System Pacing Registry.

Sharma PS, Patel NR, Ravi V, Zalavadia DV, ... Subzposh FA, Vijayaraman P
Background
Left bundle branch area pacing (LBBAP) has been shown to be a feasible option for patients requiring ventricular pacing.
Objective
The purpose of this study was to compare clinical outcomes between LBBAP and RVP among patients undergoing pacemaker implantation
Methods:
This observational registry included patients who underwent pacemaker implantations with LBBAP or RVP for bradycardia indications between April 2018 and October 2020. The primary composite outcome included all-cause mortality, heart failure hospitalization (HFH), or upgrade to biventricular pacing. Secondary outcomes included the composite endpoint among patients with a prespecified burden of ventricular pacing and individual outcomes.
Results
A total of 703 patients met inclusion criteria (321 LBBAP and 382 RVP). QRS duration during LBBAP was similar to baseline (121 ± 23 ms vs 117 ± 30 ms; P = .302) and was narrower compared to RVP (121 ± 23 ms vs 156 ± 27 ms; P <.001). The primary composite outcome was significantly lower with LBBAP (10.0%) compared to RVP (23.3%) (hazard ratio [HR] 0.46; 95%T confidence interval [CI] 0.306-0.695; P <.001). Among patients with ventricular pacing burden >20%, LBBAP was associated with significant reduction in the primary outcome compared to RVP (8.4% vs 26.1%; HR 0.32; 95% CI 0.187-0.540; P <.001). LBBAP was also associated with significant reduction in mortality (7.8% vs 15%; HR 0.59; P = .03) and HFH (3.7% vs 10.5%; HR 0.38; P = .004).
Conclusion
LBBAP resulted in improved clinical outcomes compared to RVP. Higher burden of ventricular pacing (>20%) was the primary driver of these outcome differences.

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

Heart Rhythm: 02 Sep 2021; epub ahead of print
Sharma PS, Patel NR, Ravi V, Zalavadia DV, ... Subzposh FA, Vijayaraman P
Heart Rhythm: 02 Sep 2021; epub ahead of print | PMID: 34481985
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Impact:
Abstract

Intracellular uptake of agents that block the hERG channel can confound the assessment of QT interval prolongation and arrhythmic risk.

Burashnikov A, Barajas-Martinez H, Cox R, Demitrack MA, ... Kowey P, Antzelevitch C
Background
Oliceridine is a biased ligand at the μ-opioid receptor recently approved for the treatment of acute pain. In a thorough QT study, corrected QT (QTc) prolongation displayed peaks at 2.5 and 60 minutes after a supratherapeutic dose. The mean plasma concentration peaked at 5 minutes, declining rapidly thereafter.
Objective
The purpose of this study was to examine the basis for the delayed effect of oliceridine to prolong the QTc interval.
Methods
Repolarization parameters and tissue accumulation of oliceridine were evaluated in rabbit left ventricular wedge preparations over a period of 5 hours. The effects of oliceridine on ion channel currents were evaluated in human embryonic kidney and Chinese hamster ovary cells. Quinidine was used as a control.
Results
Oliceridine and quinidine produced a progressive prolongation of the QTc interval and action potential duration over a period of 5 hours, paralleling slow progressive tissue uptake of the drugs. Oliceridine caused modest prolongation of these parameters, whereas quinidine produced a prominent prolongation of action potential duration and QTc interval as well as development of early afterdepolarization (after 2 hours), resulting in a high torsades de pointes score. The 50% inhibitory concentration values for the oliceridine inhibition of the rapidly activating delayed rectifier current (human ether a-go-go current) and late sodium channel current were 2.2 and 3.45 μM when assessed after traditional acute exposure but much lower after 3 hours of drug exposure.
Conclusion
Our findings suggest that a gradual increase of intracellular access of drugs to the hERG channels as a result of their intracellular uptake and accumulation can significantly delay effects on repolarization, thus confounding the assessment of QT interval prolongation and arrhythmic risk when studied acutely. The multi-ion channel effects of oliceridine, late sodium channel current inhibition in particular, point to a low risk of devloping torsades de pointes.

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

Heart Rhythm: 01 Sep 2021; epub ahead of print
Burashnikov A, Barajas-Martinez H, Cox R, Demitrack MA, ... Kowey P, Antzelevitch C
Heart Rhythm: 01 Sep 2021; epub ahead of print | PMID: 34481984
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Impact:
Abstract

Skin sympathetic nerve activity as a biomarker of fitness.

Liu X, Kumar A, O\'Neil J, Wong J, ... Emery MS, Everett TH
Background
Exercise stress testing is frequently used to expose cardiac arrhythmias. Aerobic exercise conditioning has been used as a nonpharmacologic antiarrhythmic intervention.
Objective
The purpose of this study was to test the hypothesis that noninvasively recorded skin sympathetic nerve activity (SKNA) is increased during exercise and that SKNA response varies according to fitness levels.
Methods
Oxygen consumption (VO2) and SKNA were recorded in 39 patients undergoing an incremental exercise test. Patients were grouped by 5 levels of fitness based on age, sex, and VO2max.
Results
With exercise, all patients had a significant increase in average SKNA (aSKNA) (1.58 ± 1.12 μV to 4.50 ± 3.06 μV, P = .000) and heart rate (HR) (87.40 ± 20.42 bpm to 154.13 ± 16.82 bpm, P = .000). A mixed linear model of aSKNA was used with fixed effects of fitness, exercise time, and recovery time, and random effects of subject level intercept and slopes for exercise time and recovery times. The poor fitness group had significantly higher aSKNA than the other groups (P = .0273). For all subjects studied, aSKNA increased by 5% per minute with progression of exercise and decreased by 15% per minute with progression of recovery. The fitness variable encodes information on both comorbidities and body mass index (BMI). Once fitness level is known, comorbidities and BMI are not significantly associated with aSKNA. In all groups, aSKNA positively correlated with HR (R2 = 0.47 ± 0.23) and VO2 (R2 = 0.68 ± 0.25).
Conclusion
Fitness level determines the magnitude and time course of SKNA increase during exercise. SKNA may be a useful fitness biomarker in exercise stress testing.

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

Heart Rhythm: 01 Sep 2021; epub ahead of print
Liu X, Kumar A, O'Neil J, Wong J, ... Emery MS, Everett TH
Heart Rhythm: 01 Sep 2021; epub ahead of print | PMID: 34481982
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Impact:
Abstract

Diagnostic accuracy of D-dimer to detect left atrial thrombus in patients with atrial fibrillation: A systematic review and meta-analysis.

Diaz-Arocutipa C, Gonzales-Luna AC, Brañez-Condorena A, Hernandez AV
Background
There is conflicting evidence about the use of biomarkers to diagnose left atrial thrombus in patients with atrial fibrillation.
Objective
The purpose of this study was to assess the diagnostic accuracy of D-dimer to detect left atrial thrombus in patients with atrial fibrillation.
Methods
We searched 4 electronic databases from inception to December 16, 2020. The reference standard was left atrial thrombus detected by transesophageal echocardiography. Study quality was assessed with the Quality Assessment of Diagnostic Accuracy Studies 2 tool. We used a bivariate model to calculate the pooled sensitivity and specificity with their 95% confidence intervals (CIs). The optimal cutoff and predictive values were also estimated.
Results
Eleven cross-sectional studies involving 4380 patients were included. The median prevalence of left atrial thrombus was 12%. In 7 studies, the pooled sensitivity of D-dimer at 500 ng/mL was 50% (95% CI 26%-74%) and the pooled specificity was 88% (95% CI 76%-95%). The pooled sensitivity of age-adjusted D-dimer was 36% (95% CI 14%-66%) and the pooled specificity was 99% (95% CI 96%-99%) in 2 studies. The optimal cutoff of D-dimer was 390 ng/mL in 10 studies with a pooled sensitivity of 68% (95% CI 44%-85%) and a pooled specificity of 73% (95% CI 54%-86%). The positive and negative predictive values were 21.8% and 95.4%, respectively. The risk of bias was low or unclear for all domains. Concerns about applicability were low for almost all studies.
Conclusion
Our meta-analysis suggests that D-dimer has the potential to be useful to rule out left atrial thrombus in patients with atrial fibrillation.

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

Heart Rhythm: 31 Aug 2021; epub ahead of print
Diaz-Arocutipa C, Gonzales-Luna AC, Brañez-Condorena A, Hernandez AV
Heart Rhythm: 31 Aug 2021; epub ahead of print | PMID: 34481076
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Impact:
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 in screening for atrial fibrillation (AF) in appropriate populations. However, currently no consumer devices are capable of continuous monitoring for AF.
Objective
The purpose of this study was 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 (W-ECG) capabilities. We validated a novel W-PPG algorithm combined with a W-ECG algorithm in a free-living setting, and compared the results to those of 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 sensitivity of 87.8% (95% confidence interval [CI] 83.6%-91.0%) and specificity of 97.4% (95% CI 97.1%-97.7%) for the W-PPG algorithm (every 5-minute classification); sensitivity of 98.9% (95% CI 98.1%-99.4%) and specificity of 99.3% (95% CI 99.1%-99.5%) for the W-ECG algorithm; and sensitivity of 96.9% (95% CI 93.7%-98.5%) and specificity of 99.3% (95% CI 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 compared to P-ECG (r = 0.98).
Conclusion
Our findings demonstrate that a novel algorithm using a commercially available smartwatch can continuously detect AF with excellent performance and that confirmation with W-ECG further enhances specificity. In addition, our W-PPG algorithm can estimate AF burden. Further research is needed to determine whether this algorithm is useful in screening for AF in select at-risk patients.

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

Heart Rhythm: 30 Aug 2021; 18:1482-1490
Avram R, Ramsis M, Cristal AD, Nathan V, ... Mortara D, Olgin JE
Heart Rhythm: 30 Aug 2021; 18:1482-1490 | PMID: 33838317
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Impact:
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 (PIC) remain unknown. Transient receptor potential vanilloid-1 (TRPV1) afferent fibers are implicated in the reflex processing of cardiac stress.
Objective
The purpose of this study was to determine whether cardiac TRPV1 afferent signaling promote PIC.
Methods
A PIC 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 control (n = 6). We examined early-stage (4 weeks after implantation; n = 5) and late-stage PIC (8 weeks after implantation; n = 6). At terminal experimentation, animals underwent echocardiography, serum sampling, and physiological 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. Left ventricular ejection fraction was worse in late-stage than early-stage PIC (P <.01). At 4 weeks (early stage), left ventricular ejection fraction was higher in PVC+RTX vs PVC animals (51.7% ± 1.6% vs 45.0% ± 2.1%; P = .030), whereas 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 = .020), suggesting that RTX mitigated profibrotic pathways induced by persistent PVCs.
Conclusion
TRPV1 afferent depletion alleviates left ventricular dysfunction in early- but not late-stage PIC. This temporal effect suggests that multiple pathways promote PIC, of which TRPV1 afferents are a part.

Copyright © 2021. Published by Elsevier Inc.

Heart Rhythm: 30 Aug 2021; 18:1586-1595
Hori Y, Temma T, Wooten C, Sobowale C, ... Swid M, Ajijola OA
Heart Rhythm: 30 Aug 2021; 18:1586-1595 | PMID: 33845214
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Impact:
Abstract

Effect of preprocedural pharmacologic cardioversion on pulmonary vein isolation in patients with persistent atrial fibrillation.

Okawa K, Hara S, Morimoto T, Tsushima R, ... Morita H, Ito H
Background
The optimal strategy for catheter ablation of persistent atrial fibrillation (PeAF) remains unknown. A preprocedural additive treatment for patients undergoing pulmonary vein isolation (PVI) alone to optimize catheter ablation should be investigated.
Objective
The purpose of this study was to determine whether pharmacologic cardioversion with a fixed low-dose antiarrhythmic drug (AAD) before ablation could stratify the long-term outcome of a PVI-alone strategy.
Methods
We conducted a prospective cohort study of PeAF patients who underwent PVI using contact force-sensing catheters. No substrate modification was performed. Fixed low-dose bepridil was administered before ablation for cardioversion and patients were classified into 2 groups based on obtaining sinus rhythm (SR). The rate of recurrence of atrial fibrillation (AF) and/or atrial tachycardia (AT) within 36 months was compared between the 2 groups.
Results
Among the 303 PeAF patients who received the AAD, 102 returned to SR (SR group), and the other 201 had persistence of AF (non-SR group). AF persistence duration at baseline and during bepridil administration was similar between the 2 groups. The SR group had a significantly lower 36-month AF/AT recurrence rate than the non-SR group (17 [22.2%] vs 55 [34.0%], log-rank P = .022). AT-type recurrence was observed in 16 patients (2 [3.3%] in the SR group vs 14 [8.9%] in the non-SR group; log-rank P = .051). Nonresponse to AAD was an independent predictor of AF/AT recurrence after adjusting for other risk factors (hazard ratio 1.34; 95% confidence interval 1.01-1.77; P = .040).
Conclusion
Preprocedural pharmacologic cardioversion could be a useful determinant for patients with treatable PeAF by PVI alone.

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

Heart Rhythm: 30 Aug 2021; 18:1473-1479
Okawa K, Hara S, Morimoto T, Tsushima R, ... Morita H, Ito H
Heart Rhythm: 30 Aug 2021; 18:1473-1479 | PMID: 33932587
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Impact:
Abstract

The precordial R\' wave: A novel discriminator between cardiac sarcoidosis and arrhythmogenic right ventricular cardiomyopathy in patients presenting with ventricular tachycardia.

Hoogendoorn JC, Venlet J, Out YNJ, Man S, ... Stevenson WG, Zeppenfeld K
Background
Cardiac sarcoidosis (CS) with right ventricular (RV) involvement can mimic arrhythmogenic right ventricular cardiomyopathy (ARVC). Histopathological differences may result in disease-specific RV activation patterns detectable on the 12-lead electrocardiogram. Dominant subepicardial scar in ARVC leads to delayed activation of areas with reduced voltages, translating into terminal activation delay and occasionally (epsilon) waves with a small amplitude. Conversely, patchy transmural RV scar in CS may lead to conduction block and therefore late activated areas with preserved voltages reflected as preserved R\' waves.
Objective
The purpose of this study was to evaluate the distinct terminal activation patterns in precordial leads V1 through V3 as a discriminator between CS and ARVC.
Methods
Thirteen patients with CS affecting the RV and 23 patients with gene-positive ARVC referred for ventricular tachycardia ablation were retrospectively included in a multicenter approach. A non-ventricular-paced 12-lead surface electrocardiogram was analyzed for the presence and the surface area of the R\' wave (any positive deflection from baseline after an S wave) in leads V1 through V3.
Results
An R\' wave in leads V1 through V3 was present in all patients with CS compared to 11 (48%) patients with ARVC (P = .002). An algorithm including a PR interval of ≥220 ms, the presence of an R\' wave, and the surface area of the maximum R\' wave in leads V1 through V3 of ≥1.65 mm2 had 85% sensitivity and 96% specificity for diagnosing CS, validated in a second cohort (18 CS and 40 ARVC) with 83% sensitivity and 88% specificity.
Conclusion
An easily applicable algorithm including PR prolongation and the surface area of the maximum R\' wave in leads V1 through V3 of ≥1.65 mm2 distinguishes CS from ARVC. This QRS terminal activation in precordial leads V1 through V3 may reflect disease-specific scar patterns.

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

Heart Rhythm: 30 Aug 2021; 18:1539-1547
Hoogendoorn JC, Venlet J, Out YNJ, Man S, ... Stevenson WG, Zeppenfeld K
Heart Rhythm: 30 Aug 2021; 18:1539-1547 | PMID: 33957319
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Impact:
Abstract

Gain in real-world cardiac resynchronization therapy efficacy with SyncAV dynamic optimization: Heart failure hospitalizations and costs.

Varma N, Hu Y, Connolly AT, Thibault B, ... Nabutovsky Y, Zareba W
Background
SyncAV, a device-based cardiac resynchronization therapy (CRT) algorithm, promotes electrical optimization by dynamically adjusting atrioventricular intervals.
Objective
The purpose of this study was to evaluate the impact of SyncAV on heart failure hospitalizations (HFHs) and related costs in a real-world CRT cohort.
Methods
Patients with SyncAV-capable CRT devices followed by remote monitoring and enrolled in Medicare fee-for-service for at least 1 year preimplant and up to 2 years postimplant were studied. Patients with SyncAV OFF were 4:1 matched to those with SyncAV ON on preimplant HFH rate, demographics, comorbidities, disease etiology, and left bundle branch block. HFHs were determined from the primary diagnosis of inpatient hospitalizations, and the cost for each event was the sum of Medicare, supplemental insurance, and patient payment.
Results
After 4:1 propensity score matching, 3630 patients were studied (mean age 75 ± 8 years; 1386 [38%] female), including 726 (25%) patients with SyncAV ON. The pre-CRT HFH rate was 0.338 HFH events per patient-year. Overall, CRT diminished the HFH rate to 0.204 events per patient-year (P < .001). SyncAV elicited a larger reduction in HFH rate (SyncAV ON: hazard ratio [HR] 0.52; 95% confidence interval [CI] 0.41-0.66; P < .001 and SyncAV OFF: HR 0.68; 95% CI 0.59-0.77; P < .001). After 2 years, the HFH rate was lower in the SyncAV ON group than in the SyncAV OFF group (0.143 HFHs per patient-year vs 0.193 HFHs per patient-year; HR 0.70; 95% CI 0.55-0.89; P = .003) and fewer HFHs were followed by 30-day HFH readmissions (4.41% vs 7.68%; P = .003) and 30-day all-cause hospital readmissions (7.04% vs 10.01%; P = .010). The total 2-year HFH-associated costs per patient were lower with SyncAV ON (difference $1135; 90% CI $93-$2109; P = .038).
Conclusion
This large, real-world, propensity score-matched study demonstrates that SyncAV CRT is associated with significantly reduced HFHs and associated costs, incremental to standard CRT.

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

Heart Rhythm: 30 Aug 2021; 18:1577-1585
Varma N, Hu Y, Connolly AT, Thibault B, ... Nabutovsky Y, Zareba W
Heart Rhythm: 30 Aug 2021; 18:1577-1585 | PMID: 33965608
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Impact:
Abstract

Double loop ventricular tachycardia activation patterns with single loop mechanisms: Asymmetric entrainment responses during \"pseudo-figure-of-eight\" reentry.

Nishimura T, Upadhyay GA, Aziz ZA, Beaser AD, ... Nayak HM, Tung R
Background
The classical paradigm of scar-related reentrant ventricular tachycardia (VT) features a circuit with a double loop figure-of-eight (F8) activation pattern.
Objective
The purpose of this study was to interrogate VT circuits with F8 activation patterns by entrainment mapping to differentiate an active loop from a passive loop.
Methods
Sixty VT circuits with >90% of tachycardia cycle length delineated in high resolution were retrospectively analyzed in 55 patients (nonischemic 49%). A pseudo-F8 VT circuit was defined as a double loop activation pattern driven by a single loop mechanism with a passive loop that yields a long postpacing interval (postpacing interval - tachycardia cycle length ≥ 30 ms).
Results
Single loop activation patterns were observed in 33% (n = 20). Of 40 circuits with F8 patterns by activation mapping, 20 were studied with entrainment mapping, where a passive loop was identified by a long postpacing interval in 50%. In 6 circuits where entrainment mapping was performed from both outer loop regions, all demonstrated asymmetric responses to entrainment, confirming a single loop mechanism. Entrainment from both lateral margins of the common pathway (n = 7) demonstrated an asymmetric response in 29%. In all pseudo-F8 circuits (n = 10), the shorter loop functioned as the active loop and ablation targeting the active loop side of the isthmus resulted in VT termination with a single radiofrequency application.
Conclusion
In a selected cohort, single loop mechanisms are more prevalent than double loop reentry in reentrant human VT. Half of VT circuits with double loop activation patterns can be demonstrated to be sustained by a single active loop mechanism by entrainment mapping. Ablation targeting the shorter active loop resulted in rapid termination during radiofrequency application.

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

Heart Rhythm: 30 Aug 2021; 18:1548-1556
Nishimura T, Upadhyay GA, Aziz ZA, Beaser AD, ... Nayak HM, Tung R
Heart Rhythm: 30 Aug 2021; 18:1548-1556 | PMID: 33965607
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Impact:
Abstract

Long-term survival following transvenous lead extraction: Importance of indication and comorbidities.

Mehta VS, Elliott MK, Sidhu BS, Gould J, ... Bosco P, Rinaldi CA
Background
Long-term outcomes are poorly understood, and data in patients undergoing transvenous lead extraction (TLE) are lacking.
Objective
The purpose of this study was to evaluate factors influencing survival in patients undergoing TLE depending on extraction indication.
Methods
Clinical data from consecutive patients undergoing TLE in the reference center between 2000 and 2019 were prospectively collected. The total cohort was divided into groups depending on whether there was an infective or noninfective indication for TLE. We evaluated the association of demographic, clinical, and device-related and procedure-related factors on mortality.
Results
A total of 1151 patients were included. Mean follow-up was 66 months, and mortality was 34.2% (n = 392). Of these patients, 632 (54.9%) and 519 (45.1%) were for infective and noninfective indications, respectively. A higher proportion in the infection group died (38.6% vs 28.5%; P <.001). In the total cohort, multivariable analysis demonstrated increased mortality risk with age >75 years (hazard ratio [HR] 2.98; 95% confidence interval [CI] 2.35-3.78; P <.001), estimated glomerular filtration rate <60 mL/min/1.73 m2 (HR 1.67; 95% CI 1.31-2.13; P <.001), higher cumulative comorbidity (HR 1.17; 95% CI 1.09-1.26; P <.001), reduced risk per percentage increase in left ventricular ejection fraction (HR 0.98; 95% CI 0.97-0.99; P <.001), and near unity per year of additional lead dwell time (HR 0.98; 95% CI 0.96-1.00; P = .037). Kaplan-Meier survival curves demonstrated worse prognosis, with a higher number of leads extracted and increasing comorbidities.
Conclusion
Long-term mortality for patients undergoing TLE remains high. Consensus guidelines recommend evaluating risk for major complications when determining whether to proceed with TLE. This study suggests also assessing longer-term outcomes when considering TLE in those with a high risk of medium- and long-term mortality, particularly for noninfective indications.

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

Heart Rhythm: 30 Aug 2021; 18:1566-1576
Mehta VS, Elliott MK, Sidhu BS, Gould J, ... Bosco P, Rinaldi CA
Heart Rhythm: 30 Aug 2021; 18:1566-1576 | PMID: 33984526
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Impact:
Abstract

Interatrial septal tachycardias following atrial fibrillation ablation or cardiac surgery: Electrophysiological features and ablation outcomes.

Garg L, Pothineni NVK, Arroyo A, Rodriguez D, ... Saenz LC, Santangeli P
Background
Interatrial septal tachycardias (IAS-ATs) following atrial fibrillation (AF) ablation or cardiac surgery are rare, and their management is challenging.
Objective
The purpose of this study was to investigate the electrophysiological features and outcomes associated with catheter ablation of IAS-AT.
Methods
We screened 338 patients undergoing catheter ablation of ATs following AF ablation or cardiac surgery. Diagnosis of IAS-AT was based on activation mapping and analysis of response to atrial overdrive pacing.
Results
Twenty-nine patients (9%) had IAS-AT (cycle length [CL] 311 ± 104 ms); 16 (55%) had prior AF ablation procedures (median 3; range 1-5), 3 (10%) had prior surgical maze, and 12 (41%) had prior cardiac surgery (including atrial septal defect surgical repair in 5 and left atrial myxoma resection in 1). IAS substrate abnormalities were documented in all patients. Activation mapping always demonstrated a diffuse early IAS breakout with centrifugal biatrial activation, and atrial overdrive pacing showed a good postpacing interval (equal or within 25 ms of the AT CL) only at 1 or 2 anatomically opposite IAS sites in all cases. Ablation was acutely successful in 27 patients (93%) (from only the right IAS in 2, only the left IAS in 9, both IAS sides with sequential ablation in 13, and both IAS sides with bipolar ablation in 3). After median follow-up of 15 (6-52) months, 17 patients (59%) remained free from recurrent arrhythmias.
Conclusion
IAS-ATs are rare and typically occur in patients with evidence of IAS substrate abnormalities and prior cardiac surgery. Catheter ablation can be challenging and may require sequential unipolar ablation or bipolar ablation.

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

Heart Rhythm: 30 Aug 2021; 18:1491-1499
Garg L, Pothineni NVK, Arroyo A, Rodriguez D, ... Saenz LC, Santangeli P
Heart Rhythm: 30 Aug 2021; 18:1491-1499 | PMID: 33984525
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Impact:
Abstract

Venous anatomy of the left ventricular summit: Therapeutic implications for ethanol infusion.

Tavares L, Fuentes S, Lador A, Da-Wariboko A, ... Dave AS, Valderrábano M
Background
Venous ethanol ablation (VEA) is effective for treatment of left ventricular (LV) summit (LVS) arrhythmias. The LVS venous anatomy is poorly understood and has inconsistent nomenclature.
Objective
The purpose of this study was to delineate the LVS venous anatomy by selective venography and 3-dimensional (3D) mapping during VEA and by venous-phase coronary computed tomographic angiography (vCTA).
Methods
We analyzed (1) LVS venograms and 3D maps of 53 patients undergoing VEA; and (2) 3D reconstructions of 52 vCTAs, tracing LVS veins.
Results
Angiography identified the following LVS veins: (1) LV annular branch of the great cardiac vein (GCV) (19/53); (2) septal (rightward) branches of the anterior ventricular vein (AIV) (53/53); and (3) diagonal branches of the AIV (51/53). Collateral connections between LVS veins and outflow, conus, and retroaortic veins were common. VEA was delivered to target arrhythmias in 38 of 53 septal, 6 of 53 annular, and 2 of 53 diagonal veins. vCTA identified LVS veins (range 1-5) in a similar distribution. GCV-AIV transition could either form an angle close to the left main artery bifurcation (n = 16; 88° ± 13°) or cut diagonally (n = 36; 133°±12°) (P ≤.001). Twenty-one patients had LV annular vein. In 28 patients only septal LVS veins were visualized in vCTA, in 2 patients only diagonal veins and in 22 patients both septal and diagonal veins were seen. In 39 patients the LVS veins reached the outflow tracts and their vicinity.
Conclusion
We provide a systematic atlas and nomenclature of LVS veins related to arrhythmogenic substrates. vCTA can be useful for noninvasive evaluation of LVS veins before ethanol ablation.

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

Heart Rhythm: 30 Aug 2021; 18:1557-1565
Tavares L, Fuentes S, Lador A, Da-Wariboko A, ... Dave AS, Valderrábano M
Heart Rhythm: 30 Aug 2021; 18:1557-1565 | PMID: 33989783
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Impact:
Abstract

P-wave signal-averaged electrocardiography: Reference values, clinical correlates, and heritability in the Framingham Heart Study.

Kornej J, Magnani JW, Preis SR, Soliman EZ, ... Benjamin EJ, Lin H
Background
P-wave signal-averaged electrocardiography (P-SAECG) quantifies atrial electrical activity. P-SAECG measures and their clinical correlates and heritability have had limited characterization in community-based cohorts.
Objective
The purpose of this study was to (1) establish reference values; (2) identify clinical risk factors associated with P-SAECG; and (3) estimate genetic heritability for P-SAECG traits.
Methods
We performed P-SAECG in 2 generations of Framingham Heart Study participants. We performed backward elimination regression models to assess associations of clinical factors with each SAECG trait (P-wave [PW] duration, root mean square voltage in terminal 40 ms [RMS40], terminal 30 ms RMS30, terminal 20 ms RMS20, RMS PW, and PW integral). We estimated the adjusted genetic heritability of P-SAECG measures using the Sequential Oligogenic Linkage Analysis Routines (SOLAR) program.
Results
We included 4307 participants (age 55 ± 14 years; 56% female). The reference values were derived from 1752 participants without cardiovascular risk factors. Median (2.5th percentile; 97.5th percentile) total PW duration was 118 ms (93; 146) in women and 128 ms (104; 158) in men in the reference sample, and 121 ms (94; 151) in women and 129 ms (103; 159) in the entire study cohort (broad sample). In the broad sample, after adjusting for age and sex, total PW duration was positively associated with height, weight, prevalent heart failure, history of atrial fibrillation (AF), and atrioventricular node blockers, and negatively associated with smoking, waist circumference, heart rate, and diabetes. The estimated heritability of P-SAECG traits was moderate, ranging from 11.9% for RMS30 to 24.9% for PW integral.
Conclusion
P-SAECG traits are associated with multiple AF-related risk factors and are moderately heritable.

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

Heart Rhythm: 30 Aug 2021; 18:1500-1507
Kornej J, Magnani JW, Preis SR, Soliman EZ, ... Benjamin EJ, Lin H
Heart Rhythm: 30 Aug 2021; 18:1500-1507 | PMID: 33989782
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Impact:
Abstract

Renal denervation prevents myocardial structural remodeling and arrhythmogenicity in a chronic kidney disease rabbit model.

Liu SH, Lo LW, Chou YH, Lin WL, ... Yamada S, Chen SA
Background
The electrophysiological (EP) effects and safety of renal artery denervation (RDN) in chronic kidney disease (CKD) are unclear.
Objective
The purpose of this study was to investigate the arrhythmogenicity of RDN in a rabbit model of CKD.
Methods
Eighteen New Zealand white rabbits were randomized to control (n = 6), CKD (n = 6), and CKD-RDN (n = 6) groups. A 5/6 nephrectomy was selected for the CKD model. RDN was applied in the CKD-RDN group. All rabbits underwent cardiac EP studies for evaluation. Immunohistochemistry, myocardial fibrosis, and renal catecholamine levels were evaluated.
Results
The CKD group (34.8% ± 9.2%) had a significantly higher ventricular arrhythmia (VA) inducibility than the control (8.6% ± 3.8%; P <.01) and CKD-RDN (19.5% ± 6.3%; P = .01) groups. In the CKD-RDN group, ventricular fibrosis was significantly decreased compared to the CKD group (7.4% ± 2.0 % vs 10.4% ± 3.7%; P = .02). Sympathetic innervation in the CKD group was significantly increased compared to the control and CKD-RDN groups [left ventricle: 4.1 ± 1.8 vs 0.8 ± 0.5 (102 μm2/mm2), P <.01; 4.1 ± 1.8 vs 0.9± 0.6 (102 μm2/mm2), P <.01; right ventricle: 3.6 ± 1.0 vs 1.0 ± 0.4 (102 μm2/mm2), P <.01; 3.6 ± 1.0 vs 1.0 ± 0.5 (102 μm2/mm2), P <.01].
Conclusion
Neuromodulation by RDN demonstrated protective effects with less structural and electrical remodeling, leading to attenuated VAs. In a rabbit model of CKD, RDN plays a therapeutic role by lowering the risk of VA caused by autonomic dysfunction.

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

Heart Rhythm: 30 Aug 2021; 18:1596-1604
Liu SH, Lo LW, Chou YH, Lin WL, ... Yamada S, Chen SA
Heart Rhythm: 30 Aug 2021; 18:1596-1604 | PMID: 33992732
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Impact:
Abstract

In vitro modeling accurately predicts cardiac lead fracture at 10 years.

Wilkoff BL, Donnellan E, Himes A, Ben Johnson W, ... Lexcen DR, Crossley GH
Background
Development of a cardiac lead fracture model has the potential to differentiate well-performing lead designs from poor performing ones and could aid in future lead development.
Objective
The purpose of this study was to demonstrate a predictive model for lead fracture and validate the results generated by the model by comparing them to observed 10-year implantable cardioverter-defibrillator lead fracture-free survival.
Methods
The model presented here uses a combination of in vivo patient data, in vitro conductor fatigue test data, and statistical simulation to predict the fracture-free survival of cardiac leads. The model was validated by comparing the results to human clinical performance data from the Medtronic Sprint Fidelis (Minneapolis, MN) models 6931 (single coil, active fixation) and 6949 (dual coil, active fixation), as well as the Quattro model 6947 (dual coil, active fixation).
Results
Median patient age in the single coil Fidelis 6931 population (64 years) was less than in the dual coil Fidelis 6949 and Quattro populations (68 years). Modeled and observed fracture-free survival for Quattro (>97%) was superior to that for Fidelis (<94%). The modeled survival agreed with the observed fracture-free survival data. The average model error was 0.3% (SD 1.2%).
Conclusion
This model for cardiac lead fracture-free survival using in vivo lead bending measurements and in vitro bench testing can be used to predict lead performance as observed by alignment with field survival data.

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

Heart Rhythm: 30 Aug 2021; 18:1605-1612
Wilkoff BL, Donnellan E, Himes A, Ben Johnson W, ... Lexcen DR, Crossley GH
Heart Rhythm: 30 Aug 2021; 18:1605-1612 | PMID: 33992730
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Impact:
Abstract

Arrhythmia prevalence among patients with polymyositis-dermatomyositis in the United States: An observational study.

Naaraayan A, Meredith A, Nimkar A, Arora G, Bharati R, Acharya P
Background
Systemic inflammation has been associated with atherosclerotic cardiovascular diseases (ASCVD) and arrhythmia occurrence in rheumatologic conditions such as rheumatoid arthritis. Polymyositis and dermatomyositis (PD) are rare rheumatologic conditions characterized by symmetrical proximal muscle weakness and, in the case of dermatomyositis, cutaneous eruption. Although there is literature associating PD with ASCVD, no population-level studies have analyzed arrhythmia risk in PD.
Objective
The purpose of this study was to assess the prevalence of arrhythmia and its subtypes by age and sex in patients with PD and to determine associations between arrhythmia and PD.
Methods
This retrospective cohort study included adults for whom hospitalizations had been recorded in the National Inpatient Sample database in the United States between 2016 and 2018. Patients with PD were matched (1:10) by age to patients without PD. Prevalence of arrhythmia was calculated in the 2 groups and compared by sex and age groups. Associations between PD and arrhythmia were determined after adjustment for common arrhythmia risk factors.
Results
From 107,001,355 hospitalizations, 32,085 adults with PD were matched to 320,850 controls. Patients with PD aged <70 years had a higher prevalence of arrhythmia and higher adjusted odds of arrhythmia compared with controls. This increased risk was only seen for supraventricular arrhythmias. Adults with PD had increased odds of in-hospital mortality if they had an arrhythmia diagnosis (odds ratio 3.3; 95% confidence interval 2.5-4.5; P <.001).
Conclusion
We found a higher prevalence and odds of arrhythmias, particularly supraventricular arrhythmias, in young and middle-aged patients with PD compared with matched controls. Arrhythmias were associated with significant mortality among patients with PD.

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

Heart Rhythm: 30 Aug 2021; 18:1516-1523
Naaraayan A, Meredith A, Nimkar A, Arora G, Bharati R, Acharya P
Heart Rhythm: 30 Aug 2021; 18:1516-1523 | PMID: 34048962
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Impact:
Abstract

Pericardial effusion requiring intervention in patients undergoing percutaneous left atrial appendage occlusion: Prevalence, predictors, and associated in-hospital adverse events from 17,700 procedures in the United States.

Munir MB, Khan MZ, Darden D, Pasupula DK, ... Reeves R, Hsu JC
Background
Left atrial appendage occlusion has shown promise in mitigating the risk of stroke in selected patients with atrial fibrillation.
Objective
The purpose of this study was to determine the real-world prevalence and in-hospital outcomes in left atrial appendage occlusion (Watchman) recipients complicated by pericardial effusion requiring percutaneous drainage or open cardiac surgery-based intervention.
Methods
Data were derived from the National Inpatient Sample database from January 2015 to December 2017. The primary outcomes assessed were the prevalence of pericardial effusion requiring intervention and in-hospital outcomes including mortality, other major complications, hospital stay > 1 day, and hospitalization costs. Predictors of pericardial effusion requiring intervention were also analyzed.
Results
Pericardial effusion requiring intervention occurred in 220 total patients (1.24%). After multivariable adjustment, pericardial effusion requiring intervention was associated with in-hospital mortality (adjusted odds ratio [aOR] 511.6; 95% confidence interval [CI] 122-2145.3), other Watchman-related major complications (aOR 1.35; 95% CI 0.83-2.19), length of stay > 1 day (aOR 17.64; 95% CI 12.56-24.77), and hospitalization cost above the median of $24,327 (aOR 3.58; 95% CI 2.61-4.91). Independent patient predictors of pericardial effusion requiring intervention from the procedure included advanced age (aOR 1.029 per 1-year increase; 95% CI 1.009-1.05 per 1-year increase), higher CHA2DS2-VASc score (aOR 1.221 per 1-point increase; 95% CI 1.083-1.377 per 1-point increase), and obesity (aOR 2.033; 95% CI 1.464-2.823).
Conclusion
In a large, contemporary real-world cohort of Watchman recipients in US practice, the prevalence of pericardial effusion requiring intervention was 1.24%. Pericardial effusion requiring intervention was associated with several adverse events including increased in-hospital mortality, other major complications, prolonged hospital stay, and hospitalization costs.

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

Heart Rhythm: 30 Aug 2021; 18:1508-1515
Munir MB, Khan MZ, Darden D, Pasupula DK, ... Reeves R, Hsu JC
Heart Rhythm: 30 Aug 2021; 18:1508-1515 | PMID: 34020049
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Impact:
Abstract

Prevalence and outcome of early recurrence of atrial tachyarrhythmias in the Cryoballoon vs Irrigated Radiofrequency Catheter Ablation (CIRCA-DOSE) study.

Steinberg C, Champagne J, Deyell MW, Dubuc M, ... Andrade JG, CIRCA-DOSE Study Investigators
Background
Early recurrence of atrial tachyarrhythmia (ERAT) is common after pulmonary vein isolation (PVI) and has been associated with an increased risk of late atrial fibrillation (AF) recurrence.
Objective
The purpose of this study was to determine the incidence and outcomes of patients experiencing ERAT after PVI using advanced-generation ablation technologies.
Methods
This is a prespecified substudy of the CIRCA-DOSE (Cryoballoon vs Irrigated Radiofrequency Catheter Ablation: Double-Short vs Standard Exposure Duration) trial, a prospective, randomized, multicenter study comparing PVI with contact force-guided radiofrequency ablation to secondary-generation cryoballoon ablation for paroxysmal AF. All study patients received an implantable cardiac monitor to allow continuous rhythm monitoring. ERAT was defined as any recurrent atrial tachyarrhythmia within the first 90 days after AF ablation.
Results
ERAT occurred in 61% of the 346 patients at a median of 12 days (range 1-90 days) after ablation. ERAF was a significant predictor of late recurrence (60.1% with ER vs 25.9% without ER; P <.001) and symptomatic atrial tachyarrhythmia (31.6% with ERAF vs 6.7% without ERAF; P <.001). Receiver operating curve analyses revealed a strong correlation between ERAT timing and burden and late recurrence. Multivariate analysis identified ER timing (hazard ratio [HR] 2.90; 95% confidence interval [CI] 1.41-5.95; P = .004) and burden (HR 1.05 per 1% ER burden; 95% CI 1.04-1.07; P <.001) as strong independent predictors of late recurrence. Incidence rate, timing, burden, and prognostic significance of ER did not differ between the study groups.
Conclusion
ERAT remains common after PVI despite use of advanced-generation ablation technologies. Early AF recurrence beyond 3 weeks after ablation is associated with increased risk of late recurrence.

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

Heart Rhythm: 30 Aug 2021; 18:1463-1470
Steinberg C, Champagne J, Deyell MW, Dubuc M, ... Andrade JG, CIRCA-DOSE Study Investigators
Heart Rhythm: 30 Aug 2021; 18:1463-1470 | PMID: 34126269
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Impact:
Abstract

Smartwatch-based detection of cardiac arrhythmias: Beyond the differentiation between sinus rhythm and atrial fibrillation.

Strik M, Ploux S, Ramirez FD, Abu-Alrub S, ... Haïssaguerre M, Bordachar P
Within the span of a few years, watches have functionally morphed from objects that tell time to wearable minicomputers that allow real-time recording of electrocardiograms (ECGs). Considerable information can be deduced from these single lead tracings, and it is now not uncommon to see patients in whom diagnostic tracings of clinically relevant but elusive arrhythmias are captured using a smartwatch. Empowering individuals to record their own ECG tracings in scenarios such as palpitations, syncope, and for risk stratification of sudden death intuitively has considerable potential, but its value remains to be robustly demonstrated. The main objective of this review is to describe the information that can be obtained from smartwatch-based single-lead ECG recordings beyond simply differentiating between sinus rhythm and atrial fibrillation. We also review the strengths and limitations of using these devices in clinical settings and offer potential solutions to address the latter.

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

Heart Rhythm: 30 Aug 2021; 18:1524-1532
Strik M, Ploux S, Ramirez FD, Abu-Alrub S, ... Haïssaguerre M, Bordachar P
Heart Rhythm: 30 Aug 2021; 18:1524-1532 | PMID: 34147700
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Impact:
Abstract

Tissues attached to retrieved leadless pacemakers: Histopathological evaluation of tissue composition in relation to implantation time and complications.

Breeman KTN, du Long R, Beurskens NEG, van der Wal AC, ... Tjong FVY, Knops RE
Background
Leadless pacemakers (LPs) have proven safe and effective, but device revisions remain necessary. Either replacing the LP or implanting a new adjacent LP is feasible. Replacement seems more appealing, but encapsulation and tissue adhesions may hamper the safety and efficacy of LP retrieval.
Objective
We determined the incidence and cellular characteristics of tissue adherent to retrieved LPs and the potential implications for end-of-life strategy.
Methods
All 15 consecutive successful Nanostim LP retrievals in a tertiary center were included. We assessed the histopathology of adherent tissue and obtained clinical characteristics.
Results
Adherent tissue was present in 14 of 15 retrievals (93%; median implantation duration 36 months; range 0-96 months). The tissue consisted of fibrosis (n = 2), fibrosis and thrombus (n = 9), or thrombus only (n = 3). In short-term retrievals (<1 year), mostly fresh thrombi without fibrosis were seen. In later retrievals, the tissue consisted of fibrosis often with organizing or lytic thrombi. Fibrosis showed different stages of organization, notably early fibrocellular and later fibrosclerotic tissue. Inflammatory cells were seen (n = 4) without signs of infection. Tricuspid valve material was retrieved in 1 patient after 36 months, resulting in increased tricuspid regurgitation.
Conclusion
Our results suggest that fibrosis and thrombus adherent to LPs are common and encapsulate the LP as seen in transvenous pacemakers. LPs may adhere to the tricuspid valve or subvalvular apparatus affecting retrieval safety. The end-of-life strategy should be optimized by incorporating risk stratification for excessive fibrotic encapsulation and adhesions.

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

Heart Rhythm: 27 Aug 2021; epub ahead of print
Breeman KTN, du Long R, Beurskens NEG, van der Wal AC, ... Tjong FVY, Knops RE
Heart Rhythm: 27 Aug 2021; epub ahead of print | PMID: 34461305
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Impact:
Abstract

Electrical abnormalities with St. Jude/Abbott pacing leads: A systematic review and meta-analysis.

Khatiwala RV, Mullins E, Fan D, Srivatsa UN, Dhruva SS, Oesterle A
Background
Although there is a paucity of contemporary data on pacemaker lead survival rates, small studies suggest that some leads may have higher malfunction rates than do others.
Objective
The purpose of this study was to determine the malfunction rates of current pacemaker leads.
Methods
A meta-analysis including studies that examined the non-implant-related lead malfunction rates of current commercially available active fixation pacemaker leads was performed. An electronic search of MEDLINE/PubMed, Scopus, and Embase was performed. DerSimonian and Laird random effects models were used.
Results
Eight studies with a total of 14,579 leads were included. Abbott accounted for 10,838 (74%), Medtronic 2510 (17%), Boston Scientific 849 (6%), and MicroPort 382 (3%) leads. The weighted mean follow-up period was 3.6 years. Lead abnormalities occurred in 5.0% of all leads, 6.1% of Abbott leads, 1.1% of Medtronic, 1.4% of Boston Scientific, and 5.5% of MicroPort. The most common lead abnormality was lead noise with normal impedance. Abbott leads were associated with an increased risk of abnormalities (relative risk [RR] 7.81; 95% confidence interval [CI] 3.21-19.04), reprogramming (RR 7.95; 95% CI 3.55-17.82), and lead revision or extraction (RR 8.91; 95% CI 3.36-23.60). Abbott leads connected to an Abbott generator had the highest abnormality rate (8.0%) followed by Abbott leads connected to a non-Abbott generator (4.7%) and non-Abbott leads connected to an Abbott generator (0.4%).
Conclusions
Abbott leads are associated with an increased risk of abnormalities compared with leads of other manufacturers, primarily manifesting as lead noise with normal impedance, and are associated with an increased risk of lead reprogramming and lead revision or extraction.

Published by Elsevier Inc.

Heart Rhythm: 27 Aug 2021; epub ahead of print
Khatiwala RV, Mullins E, Fan D, Srivatsa UN, Dhruva SS, Oesterle A
Heart Rhythm: 27 Aug 2021; epub ahead of print | PMID: 34461304
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Impact:
Abstract

Ventricular arrhythmias ablated successfully in the subvalvular interleaflet triangle between the right and left coronary cusps: Electrophysiological characteristics and catheter ablation.

Liang Z, Liu X, Li X, Zhang T, ... Wang Y, Ma C
Background
Ventricular arrhythmias (VAs) ablated successfully at the right-left subvalvular interleaflet triangle (R-L ILT) between right and left coronary cusps have not been fully characterized.
Objective
The purpose of this study was to investigate the electrophysiological characteristics of these VAs and their relationships with the left ventricular (LV) summit.
Methods
Twenty-eight VAs ablated successfully at the R-L ILT were studied.
Results
Ninety-six percent of VAs had an early precordial electrocardiographic transition. R-wave amplitude in lead V1 was relatively high (RS morphology, R-wave amplitude 0.35 ± 0.09 mV; R/S ratio 0.35 ± 0.27), whereas the morphology of lead I was R-shaped in 71% and M-shaped in 50% of VAs. Earliest potential was recorded at the R-L ILT in 13 of 28 patients and the left pulmonary sinus cusp (LC) in 6 of 28 patients. Mapping the summit communicating vein (summit-CV) failed because of anatomic or instrumental limitations in these 19 patients. In the other 9 patients, earliest potential was successfully recorded at the summit-CV, while perfect pacemapping was achieved. Poor pace mapping was achieved at the R-L ILT or LC in most patients (27/28). Target site was located at the top of the R-L ILT in all cases. A presystolic potential was present at the target site in 18 of 28 patients. A U-curve via the retrograde method was conventionally used to reach the top of the R-L ILT.
Conclusion
VAs ablated successfully at the R-L ILT have unique electrophysiological characteristics, and R-L ILT may be an endocardial anatomic ablation target for VAs originating from the base of the LV summit.

Copyright © 2021. Published by Elsevier Inc.

Heart Rhythm: 23 Aug 2021; epub ahead of print
Liang Z, Liu X, Li X, Zhang T, ... Wang Y, Ma C
Heart Rhythm: 23 Aug 2021; epub ahead of print | PMID: 34438043
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Impact:
Abstract

Outcomes and periprocedural management of cardiac implantable electronic devices in patients with carcinoid heart disease.

Ward RC, Luis SA, Shabtaie SA, Pellikka PA, ... Deshumkh AJ, DeSimone CV
Background
Carcinoid heart disease (CHD) is a rare complication of hormonally active neuroendocrine tumors that often requires surgical intervention. Data on cardiac implantable electronic device (CIED) implantation in patients with CHD are limited.
Objective
The purpose of this study was to evaluate the experience of CIED implantation in patients with CHD.
Methods
Patients with a diagnosis of CHD and a CIED procedure from January 1, 1995, through June 1, 2020, were identified using a Mayo Clinic proprietary data retrieval tool. Retrospective review was performed to extract relevant data, which included indications for implant, procedural details, complications, and mortality.
Results
A total of 27 patients (55.6% male; mean age at device implant 65.6 ± 8.8 years) with cumulative follow-up of 75 patient-years (median 1.1 years; interquartile range 0.4-4.6 years) were included for analysis. The majority of implanted devices were dual-chamber permanent pacemakers (63%). Among all CHD patients who underwent any cardiac surgery, the incidence of CIED implantation was 12%. The most common indication for implantation was high-grade heart block (66.7%). Device implant complication rates were modest (14.8%). No patient suffered carcinoid crisis during implantation, and there was no periimplant mortality. Median time from implant to death was 2.5 years, with 1-year mortality of 15%.
Conclusion
CHD is a morbid condition, and surgical valve intervention carries associated risks, particularly a high requirement for postoperative pacing needs. Our data suggest that CIED implantation can be performed relatively safely. Clinicians must be aware of the relevant carcinoid physiology and take appropriate precautions to mitigate risks.

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

Heart Rhythm: 20 Aug 2021; epub ahead of print
Ward RC, Luis SA, Shabtaie SA, Pellikka PA, ... Deshumkh AJ, DeSimone CV
Heart Rhythm: 20 Aug 2021; epub ahead of print | PMID: 34428559
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Impact:
Abstract

Clinician needs and perceptions about cardioneuroablation for recurrent vasovagal syncope: An international clinician survey.

Vandenberk B, Morillo CA, Sheldon RS, Chew DS, Aksu T, Raj SR
Background
Cardioneuroablation (CNA) targets the intrinsic cardiac autonomic nervous system ganglionated plexi located in the peri-atrial epicardial fat. There is increasing interest in CNA as a treatment of vasovagal syncope (VVS), despite no randomized clinical trial (RCT) data.
Objective
The purpose of this study was to poll the opinion on CNA) for VVS.
Methods
A REDCap (Research Electronic Data Capture) survey was administered to international physicians treating patients with VVS on their opinion about patient selection criteria, ablation approach, RCT design, and most appropriate end points for CNA procedures.
Results
The survey was completed by 118 physicians; 86% were cardiac electrophysiologists. The majority of respondents (79%) would consider referring a patient with refractory VVS for CNA, and 27% have performed CNA for VVS themselves. Most felt patient selection should require a head-up tilt test with a cardioinhibitory response (67%) and suggest a minimum age of 18 years with a median of 3 (interquartile range 2-5) episodes in the past year. There were differences in patient selection between physicians who have performed CNA themselves and those who have not. The majority felt that the ablation strategy should include both atria (70%) with an anatomical approach in combination with autonomic stimulation (85%). Performing a sham procedure in the control arm was supported by 56% of respondents, providing equipoise in RCT design. The preferred primary outcome was freedom from syncope within 1 year of follow-up.
Conclusion
There is widespread support for well-designed RCTs to confirm the hypothesized clinical benefit of CNA, provide data to guide the risk-benefit equations during patient selection, and appropriately estimate the placebo effect.

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

Heart Rhythm: 18 Aug 2021; epub ahead of print
Vandenberk B, Morillo CA, Sheldon RS, Chew DS, Aksu T, Raj SR
Heart Rhythm: 18 Aug 2021; epub ahead of print | PMID: 34419666
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Impact:
Abstract

Permanent pacemaker implantation late after transcatheter aortic valve implantation.

Elchinova E, Nozica N, Bartkowiak J, Ryffel C, ... Pilgrim T, Roten L
Background
Impairment of atrioventricular (AV) conduction may occur late after transcatheter aortic valve implantation (TAVI), and progression to complete AV block is a matter of concern.
Objective
The purpose of this study was to describe the incidence of permanent pacemaker (PPM) implantation late after TAVI.
Methods
In a prospective TAVI registry, we retrospectively identified patients with PPM implantation after hospital discharge for TAVI and analyzed serial electrocardiograms for AV conduction impairment before PPM implantation.
Results
Among 1059 patients discharged after TAVI without PPM between January 2012 and December 2017, 62 patients (5.9%) underwent PPM implantation at a median of 305 days after discharge for TAVI. Indications for PPM implantation late after TAVI were AV conduction impairment in 46 patients (74.2%); sick sinus syndrome in 10 (16.1%); cardiac resynchronization or implantable cardioverter-defibrillator indication in 2 (3.2%); and a pace and ablate strategy in 4 (6.5%). Clinical symptoms leading to PPM implantation late after TAVI included syncope in 19 patients (30.7%), presyncope in 7 (11.3%), and dyspnea in 8 (12.9%). First-degree AV block and new left bundle branch block (LBBB) after TAVI as well as valve-in-valve procedure during follow-up were independent predictors of PPM implantation late after TAVI due to AV conduction impairment.
Conclusion
PPM implantation late after TAVI is infrequent and is associated with clinical symptoms in half of patients. Impairment of AV conduction was the indication in three-quarters of patients. First-degree AV block and new LBBB after TAVI as well as valve-in-valve procedure during follow-up emerged as independent predictors.

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

Heart Rhythm: 15 Aug 2021; epub ahead of print
Elchinova E, Nozica N, Bartkowiak J, Ryffel C, ... Pilgrim T, Roten L
Heart Rhythm: 15 Aug 2021; epub ahead of print | PMID: 34411717
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Impact:
Abstract

Three-year outcome after transcatheter aortic valve implantation: Comparison of a restrictive versus a liberal strategy for pacemaker implantation.

Schoechlin S, Minners J, Schulz U, Eichenlaub M, ... Neumann FJ, Arentz T
Background
Conduction disturbances after transcatheter aortic valve implantation (TAVI) are common, heterogeneous, and frequently result in permanent pacemaker implantation (PPI). Pacemaker therapy with a high rate of right ventricular pacing is associated with heart failure, hospitalizations, and reduced quality of life.
Objective
The purpose of this study was to compare medium-term outcomes between PPI implantation strategies, as choosing the right indication for PPI is still an area of uncertainty and information on outcomes of PPI regimens beyond 1 year is rare.
Methods
We compared outcomes after 3 years between a restrictive PPI strategy, in which the lowest threshold for PPI was left bundle branch block (LBBB) (QRS >120 ms) with the presence of new atrioventricular block (PQ >200 ms), and a liberal PPI regimen, in which PPI already was performed in patients with new-onset LBBB.
Results
Between January 2014 and December 2016, TAVI was performed in 884 patients at our center. Of these, 383 consecutive, pacemaker-naive patients underwent TAVI with the liberal PPI strategy and subsequently 384 with the restrictive strategy. The restrictive strategy significantly reduced the percentage of patients undergoing PPI before discharge (17.2% vs 38.1%; P <.001). The incidence of the primary endpoint (all-cause-mortality and hospitalization for heart failure) after 3 years was similar in both groups (30.7% vs 35.2%; P = .242), as was all-cause-mortality (26.6% vs 29.2%; P = .718). Overall, patients who required PPI post-TAVI had significantly more hospitalizations due to heart failure (14.8% vs 7.8%; P = .004).
Conclusion
A restrictive PPI strategy after TAVI reduces PPI significantly and is safe in medium-term follow-up over 3 years.

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

Heart Rhythm: 13 Aug 2021; epub ahead of print
Schoechlin S, Minners J, Schulz U, Eichenlaub M, ... Neumann FJ, Arentz T
Heart Rhythm: 13 Aug 2021; epub ahead of print | PMID: 34400310
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Impact:
Abstract

Impacts of frailty on heart rate variability in aging mice: Roles of the autonomic nervous system and sinoatrial node.

Dorey TW, Jansen HJ, Moghtadaei M, Jamieson KL, Rose RA
Background
Heart rate variability (HRV) is determined by intrinsic sinoatrial node (SAN) activity and the autonomic nervous system (ANS). HRV is reduced in aging; however, aging is heterogeneous. Frailty, which can be measured using a frailty index (FI), can quantify health status in aging separately from chronological age.
Objective
The purpose of this study was to investigate the impacts of age and frailty on HRV in mice.
Methods
Frailty was measured in aging mice between 10 and 130 weeks of age. HRV was assessed using time domain, frequency domain, and Poincaré plot analyses in anesthetized mice at baseline and after ANS blockade, as well as in isolated atrial preparations.
Results
HRV was reduced in aged mice (90-130 weeks and 50-80 weeks old) compared to younger mice (10-30 weeks old); however, there was substantial variability within age groups. In contrast, HRV was strongly correlated with FI score regardless of chronological age. ANS blockade resulted in reductions in heart rate that were largest in 90- to 130-week-old mice and were correlated with FI score. HRV after ANS blockade or in isolated atrial preparations was increased in aged mice but again showed high variability among age groups. HRV was correlated with FI score after ANS blockade and in isolated atrial preparations.
Conclusion
HRV is reduced in aging mice in association with a shift in sympathovagal balance and increased intrinsic SAN beating variability; however, HRV is highly variable within age groups. HRV was strongly correlated with frailty, which was able to detect differences in HRV separately from chronological age.

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

Heart Rhythm: 07 Aug 2021; epub ahead of print
Dorey TW, Jansen HJ, Moghtadaei M, Jamieson KL, Rose RA
Heart Rhythm: 07 Aug 2021; epub ahead of print | PMID: 34371195
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Impact:
Abstract

Lower rate limit for pacing by cardiac resynchronization defibrillators: Should lower rate programming be reconsidered?

Sharma AD, Wilkoff BL, Richards M, Wold N, ... Perschbacher D, Olshansky B
Background
No real-world large database associates lower rate limit (LRL) programming and survival of subjects with cardiac resynchronization therapy-defibrillators (CRT-Ds).
Objective
The purpose of this study was to test the hypothesis that lower LRL programming is independently associated with survival, and that LRL and heart rate score (HrSc) are associated.
Methods
All dual-chamber CRT-D devices in the Remote Patient Monitoring (RPM) ALTITUDE database (2006-2011) were queried. Baseline HrSc was defined as the percentage of all atrial sensed and paced beats in the tallest 10-beat histogram bin postimplant. LRL was assessed during repeated RPM uploads. Using a Cox model multivariable analysis, relationships between LRL, survival, HrSc, and other variables were evaluated. Survival was determined by query of death indices.
Results
Data analyzed included 61,881 subjects (mean follow-up 2.9 years). LRL ranged from 40 to 85 bpm. Baseline lower LRL was associated with younger age, less atrial fibrillation, female sex, and lower HrSc (P <.001 for all covariates). Lower LRL was associated with improved survival, with LRL 40 associated with the largest survival benefit. This was significant for all 3 HrSc subgroups (P <.001). An interaction between HrSc and LRL was observed, with the largest survival difference between HrSc groups observed at LRL-40 (P <.001).
Conclusion
LRL programming and HrSc were associated, and lower values of both were associated with improved survival in a large database of CRT-D subjects. Relationships between survival, LRL programming, and HrSc merit further study.

Copyright © 2021. Published by Elsevier Inc.

Heart Rhythm: 07 Aug 2021; epub ahead of print
Sharma AD, Wilkoff BL, Richards M, Wold N, ... Perschbacher D, Olshansky B
Heart Rhythm: 07 Aug 2021; epub ahead of print | PMID: 34371194
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Impact:
Abstract

Discrete sites of frequent premature ventricular complexes cluster within the infarct border zone and coincide with high frequency of delayed afterdepolarizations under adrenergic stimulation.

Amoni M, Claus P, Dries E, Nagaraju C, ... Sipido KR, Willems R
Background
Sympathetic activation in ischemic heart disease can cause lethal arrhythmias. These often are preceded by premature ventricular complexes (PVCs), which at the cellular level could result from delayed afterdepolarizations.
Objective
The purpose of this study was to identify and map vulnerable areas for arrhythmia initiation after myocardial infarction (MI) and to explore the link between PVCs and cellular events.
Methods
Anterior-septal wall MI was induced by 120 minutes of coronary occlusion followed by reperfusion (27 MI and 16 sham pigs). After 4 weeks, EnSite™ electroanatomic mapping combined with imaging was performed to precisely locate PVC sites of origin and subsequently record monophasic action potentials. Cardiomyocytes were isolated from different regions to study regional cellular remodeling. Isoproterenol was used as a surrogate for adrenergic stimulation both in vivo and in cardiomyocytes.
Results
PVCs originated from the MI border zone (BZ) and occurred at discrete areas with clusters of PVCs within the BZ. At these sites, frequent delayed afterdepolarizations and occasional associated spontaneous action potentials translating to a PVC were present. Cardiomyocytes isolated from the MI BZ exhibited more spontaneous action potentials than cardiomyocytes from remote regions. Sensitivity to adrenergic stimulation was increased in MI, in vivo and in cardiomyocytes. In awake, freely moving MI animals, frequent PVCs, ventricular arrhythmia, and sudden cardiac death occurred spontaneously at moderately elevated heart rates.
Conclusion
Post-MI, arrhythmias initiate from discrete vulnerable areas within the BZ, where delayed afterdepolarizations, related to increased adrenergic response of BZ cardiomyocytes, can generate PVCs.

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

Heart Rhythm: 07 Aug 2021; epub ahead of print
Amoni M, Claus P, Dries E, Nagaraju C, ... Sipido KR, Willems R
Heart Rhythm: 07 Aug 2021; epub ahead of print | PMID: 34371193
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Impact:
Abstract

Reappraisal of electrocardiographic criteria for localization of idiopathic outflow region ventricular arrhythmias.

Gabriels JK, Abdelrahman M, Nambiar L, Kim J, ... Lerman BB, Cheung JW
Background
Electrocardiographic (ECG) criteria have been proposed to localize the site of origin of outflow region ventricular arrhythmias (VAs). Many factors influence the QRS morphology of VAs and may limit the accuracy of these criteria.
Objective
The purpose of this study was to assess the accuracy of ECG criteria that differentiate right from left outflow region VAs and localize VAs within the aortic sinus of Valsalva (ASV).
Methods
One hundred one patients (mean age 52 ± 16 years; 55 [54%] women) undergoing catheter ablation of right ventricular outflow tract (RVOT) or ASV VAs with a left bundle branch block, inferior axis morphology were studied. ECG measurements including V2 transition ratio, transition zone index, R-wave duration index, R/S amplitude index, V2S/V3R index, V1-3 QRS morphology, R-wave amplitude in the inferior leads were tabulated for all VAs. Comparisons were made between the predicted site of origin using these criteria and the successful ablation site.
Results
Patients had successful ablation of 71 RVOT and 38 ASV VAs. For the differentiation of RVOT from ASV VAs, the positive predictive values and negative predictive values for all tested ECG criteria ranged from 42% to 75% and from 71% to 82%, respectively, with the V2S/V3R index having the largest area under the curve of 0.852. Morphological QRS criteria in leads V1 through V3 did not localize ASV VAs. The maximum R-wave amplitude in the inferior leads was the sole criterion demonstrating a significant difference between right ASV, right-left ASV commissure, and left ASV sites.
Conclusion
ECG criteria for differentiating right from left ventricular outflow region VAs and for localizing ASV VAs have a limited accuracy.

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

Heart Rhythm: 07 Aug 2021; epub ahead of print
Gabriels JK, Abdelrahman M, Nambiar L, Kim J, ... Lerman BB, Cheung JW
Heart Rhythm: 07 Aug 2021; epub ahead of print | PMID: 34375724
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Impact:
Abstract

Recommendations regarding cardiac stereotactic body radiotherapy for treatment refractory ventricular tachycardia.

Krug D, Blanck O, Andratschke N, Guckenberger M, ... Boldt LH, Bonnemeier H
Background
Ventricular tachycardia (VT) is a potentially lethal complication of structural heart disease. Despite optimal management, a subgroup of patients continue to suffer from recurrent VT. Recently, cardiac stereotactic body radiotherapy (CSBRT) has been introduced as a treatment option in patients with VT refractory to antiarrhythmic drugs and catheter ablation.
Objective
The purpose of this study was to establish an expert consensus regarding the conduct and use of CSBRT for refractory VT.
Methods
We conducted a modified Delphi process. Thirteen experts from institutions from Germany and Switzerland participated in the modified Delphi process. Statements regarding the following topics were generated: treatment setting, institutional expertise and technical requirements, patient selection, target volume definition, and monitoring during and after CSBRT. Agreement was rated on a 5-point Likert scale. The strength of agreement was classified as strong agreement (≥80%), moderate agreement (≥66%) or no agreement (<66%).
Results
There was strong agreement regarding the experimental status of the procedure and the preference for treatment in clinical trials. CSBRT should be conducted at specialized centers with a strong expertise in the management of patients with ventricular arrhythmias and in stereotactic body radiotherapy for moving targets. CSBRT should be restricted to patients with refractory VT with optimal antiarrhythmic medication who underwent prior catheter ablation or have contraindications. Target volume delineation for CSBRT is complex. Therefore, interdisciplinary processes that should include cardiology/electrophysiology and radiation oncology as well as medical physics, radiology, and nuclear medicine are needed. Optimal follow-up is required.
Conclusion
Prospective trials and pooled registries are needed to gain further insight into this promising treatment option for patients with refractory VT.

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

Heart Rhythm: 07 Aug 2021; epub ahead of print
Krug D, Blanck O, Andratschke N, Guckenberger M, ... Boldt LH, Bonnemeier H
Heart Rhythm: 07 Aug 2021; epub ahead of print | PMID: 34380072
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Impact:
Abstract

Structure and function of the ventricular tachycardia isthmus.

Ciaccio EJ, Anter E, Coromilas J, Wan EY, ... Peters NS, Garan H
Catheter ablation of postinfarction reentrant ventricular tachycardia (VT) has received renewed interest owing to the increased availability of high-resolution electroanatomic mapping systems that can describe the VT circuits in greater detail, and the emergence and need to target noninvasive external beam radioablation. These recent advancements provide optimism for improving the clinical outcome of VT ablation in patients with postinfarction and potentially other scar-related VTs. The combination of analyses gleaned from studies in swine and canine models of postinfarction reentrant VT, and in human studies, suggests the existence of common electroanatomic properties for reentrant VT circuits. Characterizing these properties may be useful for increasing the specificity of substrate mapping techniques and for noninvasive identification to guide ablation. Herein, we describe properties of reentrant VT circuits that may assist in elucidating the mechanisms of onset and maintenance, as well as a means to localize and delineate optimal catheter ablation targets.

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

Heart Rhythm: 05 Aug 2021; epub ahead of print
Ciaccio EJ, Anter E, Coromilas J, Wan EY, ... Peters NS, Garan H
Heart Rhythm: 05 Aug 2021; epub ahead of print | PMID: 34371192
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Impact:
Abstract

Cardiovascular exercise as a treatment of postural orthostatic tachycardia syndrome: A pragmatic treatment trial.

Gibbons CH, Silva G, Freeman R
Background
Postural orthostatic tachycardia syndrome (POTS) is a heterogeneous disorder of orthostatic intolerance with few proven treatments.
Objective
The purpose of this study was to determine the efficacy of an unsupervised at-home training regimen for the treatment of POTS.
Methods
We reviewed the medical records including autonomic function testing, symptom scores, and activities of daily living in individuals with POTS who were invited to participate in a 6-month outpatient cardiovascular exercise program.
Results
Seventy-seven individuals were invited (invited group), 48 of 77 (62%) participated (treated group) and 43 of 77 (56%) of those completed. Twenty-nine of 77 (38%) did not participate (control group). After 6 months, 11 of 48 (23%) individuals in the treated group met heart rate criteria for POTS compared with 27 of 29 (93%) in the control group (χ2 test, P < .0001). Supine heart rate (68 ± 8 beats/min vs 77 ± 10 beats/min; P < .001) and standing heart rate (95 ± 11 beats/min vs 115 ± 10 beats/min; P < .001) decreased in the treated group compared with the control group. The frequency of syncope decreased in the treated group (P < .001). An improvement in the EuroQol perceived quality of life scale score was detected in the treated group (61 ± 15 vs 71 ± 12 after 6 months, P < .001) compared with the control group (64 ± 9 vs 66 ± 8 after 6 months; P = .52).
Conclusion
In this study, we report a successful pragmatic clinical trial of an outpatient exercise protocol in a tertiary care referral population that significantly improved cardiovascular function and quality of life in patients with POTS.

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

Heart Rhythm: 30 Jul 2021; 18:1361-1368
Gibbons CH, Silva G, Freeman R
Heart Rhythm: 30 Jul 2021; 18:1361-1368 | PMID: 33482385
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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 and acetaminophen for analgesia.

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

Heart Rhythm: 30 Jul 2021; 18:1326-1335
Romero J, Bello J, Díaz JC, Grushko M, ... Natale A, Di Biase L
Heart Rhythm: 30 Jul 2021; 18:1326-1335 | PMID: 33684548
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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, Flethøj 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: 30 Jul 2021; 18:1384-1391
Linz B, Sattler SM, Flethøj M, Høtbjerg Hansen ME, ... Tfelt-Hansen J, Jespersen T
Heart Rhythm: 30 Jul 2021; 18:1384-1391 | PMID: 33722764
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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 (527 female (52.7%); 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: 30 Jul 2021; 18:1272-1278
Issa ZF
Heart Rhythm: 30 Jul 2021; 18:1272-1278 | PMID: 33781982
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Impact:
Abstract

Left-axis deviation in patients with nonischemic 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 anatomic axis.
Objective
The purpose of this study was to clarify the mechanism(s) responsible for LAD in patients with LBBB.
Methods
Twenty-nine patients with nonischemic cardiomyopathies and LBBB underwent noninvasive electrocardiographic imaging (ECGi), cardiac computed tomography, and magnetic resonance imaging in order to define ventricular electrical activation, characterize cardiac structure, and determine the cardiac anatomic axis.
Results
Sixteen patients had a normal QRS axis (NA) (mean axis 8° ± 23°), whereas 13 patients had LAD (mean axis -48° ± 13°; P <.001). Total activation times were longer in the LAD group (112 ± 25 ms vs 91 ± 14 ms; P = .01) due to delayed activation of the basal anterolateral region (107 ± 10 ms vs 81 ± 17 ms; P <.001). Left ventricular (LV) activation in patients with LAD was from apex to base, in contrast to a circumferential pattern of activation in patients with NA. Apex-to-base delay was longer in the LA group (95 ± 13 ms vs 64 ± 21 ms; P <.001) and correlated with QRS frontal axis (R2 = 0.67; P <.001). Both groups were comparable with regard to LV end-diastolic volume (295 ± 84 mL vs LAD 310 ± 91 mL; P = .69), LV mass (177 ± 33 g vs LAD 180 ± 37 g; P = .83), and anatomic axis.
Conclusion
LAD in LBBB appears to be due to electrophysiological abnormalities rather than structural factors or cardiac anatomic axis.

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

Heart Rhythm: 30 Jul 2021; 18:1352-1360
Abu-Alrub S, Strik M, Huntjens P, Ramirez FD, ... Bordachar P, Ploux S
Heart Rhythm: 30 Jul 2021; 18:1352-1360 | PMID: 33831543
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Impact:
Abstract

Sporadic high pacing and shock impedance on remote monitoring in hybrid implantable cardioverter-defibrillator 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 detected by remote monitoring of hybrid cardiac implantable electronic device systems have been described recently. The clinical significance and related hazard of this phenomenon are not fully understood.
Objective
The purpose of this study was to describe the prevalence, management, and outcomes associated with hybrid implantable cardioverter-defibrillator (ICD) systems.
Methods
We collected data on patients with sporadic high lead impedance alert on remote monitoring who had undergone implantation with a hybrid ICD system between January 2015 and December 2019. Pacing thresholds, sensing and impedance values, and temporal pattern of impedance values were collected by remote monitoring, at implantation, and during an in-office visit.
Results
Among 92 patients receiving a hybrid ICD, 15 (16.3%) had high impedance alert on 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 a dual-chamber ICD, and 4 a single-chamber ICD. Three patients presented with high atrial lead impedance, 7 high right ventricular lead impedance, 1 high left ventricular impedance, and 2 high shock impedance values. All patients underwent follow-up by remote monitoring. Sporadic high impedance values were not associated with an adverse outcome or need for revision in all but 1 patient, who had continuously increasing pacing thresholds due to lead microfracture.
Conclusion
In the 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 by close follow-up.

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

Heart Rhythm: 30 Jul 2021; 18:1292-1300
Pignalberi C, Mariani MV, Castro A, Piro A, ... Fedele F, Lavalle C
Heart Rhythm: 30 Jul 2021; 18:1292-1300 | PMID: 33838316
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Impact:
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; however, their association with long term-outcomes remains poorly understood.
Objective
The purpose of this study was 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 at a median 639 (IQR 281-1017) days after implant. Following ES, 41% of patients died within 1 year. Patients who developed ES were more likely to have a history of VAs, ventricular tachycardia ablation, antiarrhythmic drug use, and perioperative mechanical circulatory support around the time of LVAD implant than patients without ES.
Conclusion
ES 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 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Heart Rhythm: 30 Jul 2021; 18:1263-1271
Rehorn MR, Black-Maier E, Loungani R, Sen S, ... Daubert JP, Piccini JP
Heart Rhythm: 30 Jul 2021; 18:1263-1271 | PMID: 33839327
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Impact:
Abstract

Flecainide-induced QRS complex widening correlates with negative inotropy.

Rabêlo 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
The purpose of this study was to examine, in an intact porcine model, the 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-minute IV administration (European Society of Cardiology guideline) and to 0.5 and 1.0 mg/kg 2-minute 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-minute area under the curve (AUC) of plasma levels was 1.4- to 2.8-fold greater for 2.0 mg/kg 10-minute IV infusion than for the lower, more rapidly delivered intratracheal and IV doses. AUC for LV contractility (ie, negative inotropic burden) was 2.2- to 3.6-fold greater for 2.0 mg/kg 10-minute 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 <.0001, for all IV doses; r2 = 0.812, P = .01, for intratracheal flecainide).
Conclusion
QRS complex widening in response to flecainide is strongly correlated with 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 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Heart Rhythm: 30 Jul 2021; 18:1416-1422
Rabêlo Evangelista AB, Monteiro FR, Nearing BD, Belardinelli L, Verrier RL
Heart Rhythm: 30 Jul 2021; 18:1416-1422 | PMID: 33848647
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Impact:
Abstract

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 is incompletely understood.
Objective
The purpose of this study was 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 overexpressing 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. Pharmacologic inhibition of Lgals3 in zebrafish reduced Wnt and transforming growth factor-β 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 galectin-3 (GAL3) release by circulating macrophages pointing toward the stabilization of desmosomal assembly at the injured regions.
Conclusion
GAL3 plays a crucial role in early AC onset through regulation of Wnt/β-catenin signaling and intercellular adhesion.

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

Heart Rhythm: 30 Jul 2021; 18:1394-1403
Cason M, Celeghin R, Marinas MB, Beffagna G, ... Basso C, Pilichou K
Heart Rhythm: 30 Jul 2021; 18:1394-1403 | PMID: 33857645
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Impact:
Abstract

Cardiac potassium inward rectifier Kir2: Review of structure, regulation, pharmacology, and arrhythmogenesis.

Reilly L, Eckhardt LL
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-of-function\" or \"loss-of-function\" mutations in KCNJ2, the gene encoding Kir2.1, cause genetic sudden cardiac death syndromes, and loss of the Kir2 current IK1 is a major contributing factor to arrhythmogenesis in failing human hearts. Here we provide a contemporary review of the functional structure, physiology, and pharmacology of Kir2 channels. 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, the presence of Kir2 channels 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 Comprehensive In Vitro Proarrhythmia Assay and drug safety testing.

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

Heart Rhythm: 30 Jul 2021; 18:1423-1434
Reilly L, Eckhardt LL
Heart Rhythm: 30 Jul 2021; 18:1423-1434 | PMID: 33857643
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Impact:
Abstract

Device-related infection in de novo transvenous implantable cardioverter-defibrillator Medicare patients.

El-Chami MF, Jacobsen CM, Griffiths RI, Hansen LK, ... Miller MA, Baddour LM
Background
Cardiac device infection is a serious complication of implantable cardioverter-defibrillator (ICD) placement and requires complete device removal with accompanying antimicrobial therapy for durable cure. Recent guidelines have highlighted the need to better identify patients at high risk of infection to assist in device selection.
Objective
To estimate the prevalence of infection in de novo transvenous (TV) ICD implants and assess factors associated with infection risk in a Medicare population.
Methods
A retrospective cohort study was conducted using 100% Medicare administrative and claims data to identify patients who underwent de novo TV-ICD implantation (July 2016-December 2017). Infection within 720 days of implantation was identified using ICD-10 codes. Baseline factors associated with infection were identified by univariable logistic regression analysis of all variables of interest, including conditions in Charlson and Elixhauser comorbidity indices, followed by stepwise selection criteria with a P ≤ .25 for inclusion in a multivariable model and a backwards, stepwise elimination process with P ≤ .1 to remain in the model. A time-to-event analysis was also conducted.
Results
Among 26,742 patients with de novo TV-ICD, 519 (1.9%) developed an infection within 720 days post implant. While more than half (54%) of infections occurred during the first 90 days, 16% of infections occurred after 365 days. Multivariable analysis revealed several significant predictors of infection: age <70 years, renal disease with dialysis, and complicated diabetes mellitus.
Conclusion
The rate of de novo TV-ICD infection was 1.9%, and identified risk factors associated with infection may be useful in device selection.

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

Heart Rhythm: 30 Jul 2021; 18:1301-1309
El-Chami MF, Jacobsen CM, Griffiths RI, Hansen LK, ... Miller MA, Baddour LM
Heart Rhythm: 30 Jul 2021; 18:1301-1309 | PMID: 33887452
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Impact:
Abstract

Utility of cardiovascular implantable electronic device-derived patient activity to predict clinical outcomes.

Rosero SZ, Younis A, Jones P, McNitt S, ... Stein K, Kutyifa V
Background
The role of cardiovascular implantable electronic device (CIED)-derived activity to predict implantable cardioverter-defibrillator (ICD) therapy or death is not known.
Objective
We aimed to assess CIED-derived activity to predict clinical outcomes.
Methods
In 1500 patients enrolled in MADIT-RIT, CIED-derived patient activity was acquired daily, then averaged for the first 30 days following randomization to predict inappropriate/appropriate therapy or death. Kaplan-Meier analysis and Cox proportional regression models were used to evaluate inappropriate/appropriate therapy, heart failure, or death by 30-day CIED-derived patient activity quintiles.
Results
There were 1463 patients with CIED activity data (98%). Patients in the highest quintile (Q5) of activity (more active) had the highest rate of inappropriate therapy, 21% at 2 years, as compared to 7%-11% in the other 4 quintiles (P < .001), a 1.75 times higher risk (95% confidence interval [CI]: 1.23-2.50, P = .002). However, patients in the lowest quintile of activity (Q1, 1 hour/day) had the highest risk of mortality, 15% in 2 years, as compared to Q2-3 (1-2 hours/day, 8%-7% mortality), and Q4-5 (>2 hours/day, 2%-3% mortality) (P < .001). Patients with the lowest level of activity (Q1) had a 2.02 times higher risk of mortality (95% CI: 1.21-3.38, P = .007), and they had an 82% higher risk of heart failure hospitalization (95% CI: 1.28-2.57, P = .001).
Conclusions
High CIED-derived 30-day median patient activity predicted inappropriate therapy, while low patient activity predicted mortality and heart failure in ICD and cardiac resynchronization therapy with defibrillator patients enrolled in MADIT-RIT. Device-derived activity assessment could serve as a useful predictor of outcomes.

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

Heart Rhythm: 30 Jul 2021; 18:1344-1351
Rosero SZ, Younis A, Jones P, McNitt S, ... Stein K, Kutyifa V
Heart Rhythm: 30 Jul 2021; 18:1344-1351 | PMID: 33887451
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Impact:
Abstract

Electrophysiology studies for predicting atrioventricular block in patients with syncope: A systematic review and meta-analysis.

Sheldon RS, Lei LY, Solbiati M, Chew DS, ... Morillo C, Sandhu RK
Background
Syncope may be caused by intermittent complete heart block in patients with bundle branch block. Electrophysiology studies (EPS) testing for infra-Hisian heart block are recommended by the European Society of Cardiology syncope guidelines on the basis of decades-old estimates of their negative predictive values (NPVs) for complete heart block.
Objective
The aim of this study was to determine the NPV of EPS for complete heart block in patients with syncope and bundle branch block.
Methods
We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and CINAHL without language restriction from database inception to October 2019 for Medical Subject Headings terms and keywords related to \"syncope,\" \"heart block,\" and \"programmed electrical stimulation.\" A random effects meta-analysis was conducted with a primary outcome of the proportion of patients with a negative EPS who later presented with complete heart block, diagnosed with surface electrocardiographic (ECG) recordings vs continuous implantable cardiac monitor (ICM).
Results
Ten reports contained 12 cohorts with 639 patients who met the inclusion criteria. The mean age was 69 ± 7 years; 35% ± 10% were women; and 85% of patients had bifascicular block. Seven cohorts recorded clinical outcomes with external ECG recordings, and 5 cohorts featured ICMs. The mean prespecified His-to-ventricle interval criterion was ≥70 ms. In studies featuring surface ECG recordings, there were 7% (95% confidence interval 7%-17%) patients who developed complete heart block compared with 29% (95% confidence interval 24%-35%) in the studies featuring ICM (P = .0001).
Conclusion
The NPV of EPS in patients with syncope and bundle branch block is 0.71, sufficiently low to question its use.

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

Heart Rhythm: 30 Jul 2021; 18:1310-1317
Sheldon RS, Lei LY, Solbiati M, Chew DS, ... Morillo C, Sandhu RK
Heart Rhythm: 30 Jul 2021; 18:1310-1317 | PMID: 33887450
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Impact:
Abstract

Contrast-enhanced image-guided lead deployment for left bundle branch pacing.

Liu X, Niu HX, Gu M, Chen X, ... Hua W, Zhang S
Background
Left bundle branch pacing (LBBP) is a novel conduction system pacing modality, but pacing lead deployment remains challenging.
Objectives
This study aimed to evaluate the feasibility of visualization-enhanced lead deployment for LBBP implantation and to assess LBBP characteristics on the basis of lead tip location.
Methods
Successful LBBP with a well-defined lead tip location by visualization of the tricuspid value annulus in 20 patients was retrospectively analyzed to develop an image-guided technique to identify the LBBP target site. This technique was then prospectively tested in 60 patients who were randomized into 2 groups, one using the standard approach (the standard group) and the other using the image-guided technique (the visualization group). The procedural details, electrophysiological characteristics, and short-term follow-up were compared between groups.
Results
LBBP was successfully achieved in 28 patients in the standard group and in 29 in the visualization group. The procedural and fluoroscopic durations in the visualization group (66.76 ± 14.62 and 7.83 ± 2.05 minutes) were significantly shorter than those in the standard group (85.46 ± 20.19 and 11.11 ± 3.51 minutes) (P < .01). The number of lead deployment attempts in the visualization group was lower than that in the standard group (2.03 ± 1.18 vs 2.96 ± 1.17; P < .01), and the proportion of left bundle branch potential recorded was higher (79.3% vs 46.4%; P = .01).
Conclusion
Using a visualization technique, the procedural and fluoroscopic durations for LBBP implantation were significantly shortened with fewer lead repositioning attempts.

Copyright © 2021 Heart Rhythm Society. All rights reserved.

Heart Rhythm: 30 Jul 2021; 18:1318-1325
Liu X, Niu HX, Gu M, Chen X, ... Hua W, Zhang S
Heart Rhythm: 30 Jul 2021; 18:1318-1325 | PMID: 33887449
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Impact:
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