Journal: Circ Arrhythm Electrophysiol

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Abstract

Sustained Monomorphic Ventricular Tachycardia in Nonischemic Heart Disease: Arrhythmia-Substrate Correlations That Inform the Approach to Ablation.

Kanagasundram A, John RM, Stevenson WG

As the population of patients with implanted defibrillators has grown, an increasing number of patients nonischemic cardiomyopathies are requiring therapy to reduce ventricular arrhythmias. Most of these arrhythmias are related to areas of ventricular scar. Although the pathophysiology of scar development is not well understood in these diseases, advances in cardiac imaging and mapping are better characterizing the scar locations that give rise to the arrhythmias. Here, we review the pathophysiologic and electrocardiographic correlations that inform ablation strategies for ventricular tachycardia in these diseases.



Circ Arrhythm Electrophysiol: 30 Oct 2019; 12:e007312
Kanagasundram A, John RM, Stevenson WG
Circ Arrhythm Electrophysiol: 30 Oct 2019; 12:e007312 | PMID: 31661970
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Abstract

Dietary Saturated Fat Promotes Arrhythmia by Activating NOX2 (NADPH Oxidase 2).

Joseph LC, Avula UMR, Wan EY, Reyes MV, ... Colecraft HM, Morrow JP
Background
Obesity and diets high in saturated fat increase the risk of arrhythmias and sudden cardiac death. However, the molecular mechanisms are not well understood. We hypothesized that an increase in dietary saturated fat could lead to abnormalities of calcium homeostasis and heart rhythm by a NOX2 (NADPH oxidase 2)-dependent mechanism.
Methods
We investigated this hypothesis by feeding mice high-fat diets. In vivo heart rhythm telemetry, optical mapping, and isolated cardiac myocyte imaging were used to quantify arrhythmias, repolarization, calcium transients, and intracellular calcium sparks.
Results
We found that saturated fat activates NOX (NADPH oxidase), whereas polyunsaturated fat does not. The high saturated fat diet increased repolarization heterogeneity and ventricular tachycardia inducibility in perfused hearts. Pharmacological inhibition or genetic deletion of NOX2 prevented arrhythmogenic abnormalities in vivo during high statured fat diet and resulted in less inducible ventricular tachycardia. High saturated fat diet activates CaMK (Ca/calmodulin-dependent protein kinase) in the heart, which contributes to abnormal calcium handling, promoting arrhythmia.
Conclusions
We conclude that NOX2 deletion or pharmacological inhibition prevents the arrhythmogenic effects of a high saturated fat diet, in part mediated by activation of CaMK. This work reveals a molecular mechanism linking cardiac metabolism to arrhythmia and suggests that NOX2 inhibitors could be a novel therapy for heart rhythm abnormalities caused by cardiac lipid overload.



Circ Arrhythm Electrophysiol: 30 Oct 2019; 12:e007573
Joseph LC, Avula UMR, Wan EY, Reyes MV, ... Colecraft HM, Morrow JP
Circ Arrhythm Electrophysiol: 30 Oct 2019; 12:e007573 | PMID: 31665913
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Abstract

Cardiovascular Predictive Value and Genetic Basis of Ventricular Repolarization Dynamics.

Ramírez J, van Duijvenboden S, Aung N, Laguna P, ... Orini M, Munroe PB
Background
Early prediction of cardiovascular risk in the general population remains an important issue. The T-wave morphology restitution (TMR), an ECG marker quantifying ventricular repolarization dynamics, is strongly associated with cardiovascular mortality in patients with heart failure. Our aim was to evaluate the cardiovascular prognostic value of TMR in a UK middle-aged population and identify any genetic contribution.
Methods
We analyzed ECG recordings from 55 222 individuals from a UK middle-aged population undergoing an exercise stress test in UK Biobank (UKB). TMR was used to measure ventricular repolarization dynamics, exposed in this cohort by exercise (TMR during exercise, TMR) and recovery from exercise (TMR during recovery, TMR). The primary end point was cardiovascular events; secondary end points were all-cause mortality, ventricular arrhythmias, and atrial fibrillation with median follow-up of 7 years. Genome-wide association studies for TMR and TMR were performed, and genetic risk scores were derived and tested for association in independent samples from the full UKB cohort (N=360 631).
Results
A total of 1743 (3.2%) individuals in UKB who underwent the exercise stress test had a cardiovascular event, and TMR was significantly associated with cardiovascular events (hazard ratio, 1.11; =5×10), independent of clinical variables and other ECG markers. TMR was also associated with all-cause mortality (hazard ratio, 1.10) and ventricular arrhythmias (hazard ratio, 1.16). We identified 12 genetic loci in total for TMR and TMR, of which 9 are associated with another ECG marker. Individuals in the top 20% of the TMR genetic risk score were significantly more likely to have a cardiovascular event in the full UKB cohort (18 997, 5.3%) than individuals in the bottom 20% (hazard ratio, 1.07; =6×10).
Conclusions
TMR and TMR genetic risk scores are significantly associated with cardiovascular risk in a UK middle-aged population, supporting the hypothesis that increased spatio-temporal heterogeneity of ventricular repolarization is a substrate for cardiovascular risk and the validity of TMR as a cardiovascular risk predictor.



Circ Arrhythm Electrophysiol: 29 Sep 2019; 12:e007549
Ramírez J, van Duijvenboden S, Aung N, Laguna P, ... Orini M, Munroe PB
Circ Arrhythm Electrophysiol: 29 Sep 2019; 12:e007549 | PMID: 31607149
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Abstract

Assessment of the 2017 AHA/ACC/HRS Guideline Recommendations for Implantable Cardioverter-Defibrillator Implantation in Cardiac Sarcoidosis.

Kazmirczak F, Chen KA, Adabag S, von Wald L, ... Akçakaya M, Shenoy C
Background
Implantable cardioverter-defibrillators are used to prevent sudden cardiac death in patients with cardiac sarcoidosis. The most recent recommendations for implantable cardioverter-defibrillator implantation in these patients are in the 2017 American Heart Association/American College of Cardiology/Heart Rhythm Society Guideline for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death. These recommendations, based on observational studies or expert opinion, have not been assessed. We aimed to assess them.
Methods
We performed a large retrospective cohort study of patients with biopsy-proven sarcoidosis and known or suspected cardiac sarcoidosis that underwent cardiovascular magnetic resonance imaging. Patients were followed for a composite end point of significant ventricular arrhythmia or sudden cardiac death. The discriminatory performance of the Guideline recommendations was tested using time-dependent receiver operating characteristic analyses. The optimal cutoff for the extent of late gadolinium enhancement predictive of the composite end point was determined using the Youden index.
Results
In 290 patients, the class I and IIa recommendations identified all patients who experienced the composite end point during a median follow-up of 3.0 years. Patients meeting class I recommendations had a significantly higher incidence of the composite end point than those meeting class IIa recommendations. Left ventricular ejection fraction (LVEF) >35% with >5.7% late gadolinium enhancement on cardiovascular magnetic resonance imaging was as sensitive as and significantly more specific than LVEF >35% with any late gadolinium enhancement. Patients meeting 2 class IIa recommendations, LVEF >35% with the need for a permanent pacemaker and LVEF >35% with late gadolinium enhancement >5.7%, had high annualized event rates. Excluding 2 class IIa recommendations, LVEF >35% with syncope and LVEF >35% with inducible ventricular arrhythmia, resulted in improved discrimination for the composite end point.
Conclusions
We assessed the Guideline recommendations for implantable cardioverter-defibrillator implantation in patients with known or suspected cardiac sarcoidosis and identified topics for future research.



Circ Arrhythm Electrophysiol: 30 Aug 2019; 12:e007488
Kazmirczak F, Chen KA, Adabag S, von Wald L, ... Akçakaya M, Shenoy C
Circ Arrhythm Electrophysiol: 30 Aug 2019; 12:e007488 | PMID: 31431050
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Abstract

Mechanisms by Which Ranolazine Terminates Paroxysmal but Not Persistent Atrial Fibrillation.

Ramirez RJ, Takemoto Y, Martins RP, Filgueiras-Rama D, ... Jalife J, Pandit SV
Background
Ranolazine inhibits Na current (I), but whether it can convert atrial fibrillation (AF) to sinus rhythm remains unclear. We investigated antiarrhythmic mechanisms of ranolazine in sheep models of paroxysmal (PxAF) and persistent AF (PsAF).
Methods
PxAF was maintained during acute stretch (N=8), and PsAF was induced by long-term atrial tachypacing (N=9). Isolated, Langendorff-perfused sheep hearts were optically mapped.
Results
In PxAF ranolazine (10 μmol/L) reduced dominant frequency from 8.3±0.4 to 6.2±0.5 Hz (<0.01) before converting to sinus rhythm, decreased singularity point density from 0.070±0.007 to 0.039±0.005 cm s (<0.001) in left atrial epicardium (LA), and prolonged AF cycle length (AFCL); rotor duration, tip trajectory, and variance of AFCL were unaltered. In PsAF, ranolazine reduced dominant frequency (8.3±0.5 to 6.5±0.4 Hz; <0.01), prolonged AFCL, increased the variance of AFCL, had no effect on singularity point density (0.048±0.011 to 0.042±0.016 cm s; =ns) and failed to convert AF to sinus rhythm. Doubling the ranolazine concentration (20 μmol/L) or supplementing with dofetilide (1 μmol/L) failed to convert PsAF to sinus rhythm. In computer simulations of rotors, reducing I decreased dominant frequency, increased tip meandering and produced vortex shedding on wave interaction with unexcitable regions.
Conclusions
PxAF and PsAF respond differently to ranolazine. Cardioversion in the former can be attributed partly to decreased dominant frequency and singularity point density, and prolongation of AFCL. In the latter, increased dispersion of AFCL and likely vortex shedding contributes to rotor formation, compensating for any rotor loss, and may underlie the inefficacy of ranolazine to terminate PsAF.



Circ Arrhythm Electrophysiol: 29 Sep 2019; 12:e005557
Ramirez RJ, Takemoto Y, Martins RP, Filgueiras-Rama D, ... Jalife J, Pandit SV
Circ Arrhythm Electrophysiol: 29 Sep 2019; 12:e005557 | PMID: 31594392
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Abstract

Activation During Sinus Rhythm in Ventricles With Healed Infarction: Differentiation Between Arrhythmogenic and Nonarrhythmogenic Scar.

Rottmann M, Kleber AG, Barkagan M, Sroubek J, ... Buxton AE, Anter E
Background
In infarct-related ventricular tachycardia (VT), the circuit often corresponds to a location characterized by activation slowing during sinus rhythm (SR). However, the relationship between activation slowing during SR and vulnerability for reentry and correlation to components of the VT circuit are unknown. This study examined the relationship between activation slowing during SR and vulnerability for reentry and correlated these areas with components of the circuit.
Methods
In a porcine model of healed infarction, the spatial distribution of endocardial activation velocity was compared between SR and VT. Isthmus sites were defined using activation and entrainment mapping as areas exhibiting diastolic activity within the circuit while bystanders were defined as areas displaying diastolic activity outside the circuit.
Results
Of 15 swine, 9 had inducible VT (5.2±3.0 per animal) while in 6 swine VT could not be induced despite stimulation from 4 RV and LV sites at 2 drive trains with 6 extra-stimuli down to refractoriness. Infarcts with VT had a greater magnitude of activation slowing during SR. A minimal endocardial activation velocity cutoff ≤0.1 m/s differentiated inducible from noninducible infarctions (=0.015). Regions of maximal endocardial slowing during SR corresponded to the VT isthmus (area under curve=0.84 95% CI, 0.78-0.90) while bystander sites exhibited near-normal activation during SR. VT circuits were complex with 41.7% exhibiting discontinuous propagation with intramural bridges of slow conduction and delayed quasi-simultaneous endocardial activation. Regions forming the VT isthmus borders had faster activation during SR while regions forming the inner isthmus were activated faster during VT.
Conclusions
Endocardial activation slowing during SR may differentiate infarctions vulnerable for VT from those less vulnerable for VT. Sites of slow activation during SR correspond to sites forming the VT isthmus but not to bystander sites.



Circ Arrhythm Electrophysiol: 29 Sep 2019; 12:e007879
Rottmann M, Kleber AG, Barkagan M, Sroubek J, ... Buxton AE, Anter E
Circ Arrhythm Electrophysiol: 29 Sep 2019; 12:e007879 | PMID: 31597477
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Abstract

Outcomes of Atrial Fibrillation Ablation in Morbidly Obese Patients Following Bariatric Surgery Compared With a Nonobese Cohort.

Donnellan E, Wazni O, Kanj M, Hussein A, ... Schauer P, Saliba W
Background
Morbid obesity is associated with unacceptable high recurrence rates following atrial fibrillation ablation. The role of risk-factor modification including weight loss and improved glycemic control in reducing arrhythmia recurrence following ablation has been highlighted in recent years. In this study, we compared arrhythmia recurrence rates in morbidly obese patients who underwent prior bariatric surgery (BS) with those of nonobese patients following atrial fibrillation ablation in addition to morbidly obese patients who did not undergo BS.
Methods
This was a single-center observational cohort study. We matched 51 morbidly obese patients [body mass index ≥40 kg/m] who had undergone prior BS in a 2:1 manner with 102 nonobese patients and 102 morbidly obese patients without prior BS on the basis of age, sex, and timing of atrial fibrillation ablation. Our primary outcome of interest was arrhythmia recurrence.
Results
From the time of BS to ablation, BS was associated with a significant reduction in body mass index (47.6±9.3 to 36.7±7; <0.0001), glycated hemoglobin (6.7±1.5 to 5.8±0.6; <0.0001), and systolic blood pressure (145±13 to 118±11; <0.0001). During a mean follow-up of 29±13 months following ablation, recurrent arrhythmia occurred in 10/51 (20%) patients in the BS group compared with 25/102 (24.5%) patients in the nonobese group and 56 (55%) patients in the non-BS morbidly obese group (<0.0001). No procedural complications were observed in the BS group.
Conclusions
Bariatric surgery is associated with a reduction in arrhythmia recurrence following atrial fibrillation ablation in morbidly obese patients to those of nonobese patients. Morbidly obese patients should be considered for BS before atrial fibrillation ablation.



Circ Arrhythm Electrophysiol: 29 Sep 2019; 12:e007598
Donnellan E, Wazni O, Kanj M, Hussein A, ... Schauer P, Saliba W
Circ Arrhythm Electrophysiol: 29 Sep 2019; 12:e007598 | PMID: 31610693
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Abstract

Prevalence and Characteristics of Subclinical Atrial Fibrillation in a Community-Dwelling Elderly Population: The ARIC Study.

Rooney MR, Soliman EZ, Lutsey PL, Norby FL, ... Alonso A, Chen LY
Background
The prevalence of subclinical atrial fibrillation (AF) in the elderly general population is unclear. We sought to define the prevalence of subclinical AF in a community-based elderly population and to characterize subclinical AF and the incremental diagnostic yield of 4 versus 2 weeks of continuous ECG monitoring.
Methods
We conducted a cross-sectional analysis within the community-based multicenter observational ARIC study (Atherosclerosis Risk in Communities) using visit 6 (2016-2017) data. The 2616 ARIC study participants who wore a leadless, ambulatory ECG monitor (Zio XT Patch) for up to 2 weeks were aged 79±5 years, 42% men, and 26% black. In a subset, 386 participants without clinically recognized AF wore the monitor twice, each time for up to 2 weeks. We characterized the prevalence of subclinical AF (ie, AF detected on the Zio XT Patch without clinically recognized AF) over 2 weeks of monitoring and the diagnostic yield of 4 versus 2 weeks of monitoring.
Results
The prevalence of subclinical AF was 2.5%; the prevalence of subclinical AF was 3.3% among white men, 2.5% among white women, 2.1% among black men, and 1.6% among black women. Subclinical AF was mostly intermittent (75%). Among those with intermittent subclinical AF, 91% had AF burden ≤10% during the monitoring period. In a subset of 386 participants without clinical AF, 78% more subclinical AF was detected by 4 weeks versus 2 weeks of ECG monitoring.
Conclusions
In our study, the prevalence of subclinical AF was lower than previously reported and monitoring beyond 2 weeks provided substantial incremental diagnostic yield. Future studies should focus on individuals with higher risk to increase diagnostic yield and consider continuous monitoring duration longer than 2 weeks.



Circ Arrhythm Electrophysiol: 29 Sep 2019; 12:e007390
Rooney MR, Soliman EZ, Lutsey PL, Norby FL, ... Alonso A, Chen LY
Circ Arrhythm Electrophysiol: 29 Sep 2019; 12:e007390 | PMID: 31607148
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Abstract

Is Vagal Response During Left Atrial Ganglionated Plexi Stimulation a Normal Phenomenon?: Comparison Between Patients With and Without Atrial Fibrillation.

Iso K, Okumura Y, Watanabe I, Nagashima K, ... Ohkubo K, Hirayama A
Background
Ganglionated plexi (GPs) play an important role in both the initiation and maintenance of atrial fibrillation (AF). GPs can be located by using continuous high-frequency stimulation (HFS) to elicit a vagal response, but whether the vagal response phenomenon is common to patients without AF is unknown.
Methods
HFS of the left atrial GPs was performed in 42 patients (aged 58.0±10.2 years) undergoing ablation for AF and 21 patients (aged 53.2±12.8 years) undergoing ablation for a left-sided accessory pathway. The HFS (20 Hz, 25 mA, 10-ms pulse duration) was applied for 5 seconds at 3 sites within the presumed anatomic area of each of the 5 major left atrial GPs (for a total of 15 sites per patient). We defined vagal response to HFS as prolongation of the R-R interval by >50% in comparison to the mean pre-HFS R-R interval averaged over 10 beats and active-GP areas as areas in which a vagal response was elicited.
Results
Overall, more active-GP areas were found in the AF group patients than in the non-AF group patients, and at all 5 major GPs, the maximum R-R interval during HFS was significantly prolonged in the AF patients. After multivariate adjustment, association was established between the total number of vagal response sites and the presence of AF. Conclusions The significant increase in vagal responses elicited in patients with AF compared with responses in non-AF patients suggests that vagal responses to HFS reflect abnormally increased GP activity specific to AF substrates.



Circ Arrhythm Electrophysiol: 29 Sep 2019; 12:e007281
Iso K, Okumura Y, Watanabe I, Nagashima K, ... Ohkubo K, Hirayama A
Circ Arrhythm Electrophysiol: 29 Sep 2019; 12:e007281 | PMID: 31610720
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Abstract

Effect of Prior Sternotomy on Outcomes in Transvenous Lead Extraction.

Tsang DC, Perez AA, Boyle TA, Carrillo RG
Background
A history of open-heart surgery has been a heavily debated topic in transvenous lead extraction. This study evaluates the impact of prior sternotomy on transvenous lead extraction outcomes.
Methods
Data for all patients undergoing transvenous lead extraction at a tertiary referral center were prospectively gathered from 2004 to 2017. Relevant clinical information was compared between patients with a history of sternotomy before transvenous lead extraction and those without. After considering baseline differences, multivariate regression, and propensity-matched analysis were performed. Outcome variables included major and minor complication rates, clinical success, and in-hospital mortality as defined by the 2017 Heart Rhythm Society consensus statement.
Results
Of 1480 patients in the study period, 455 had a prior sternotomy. When compared with patients with no prior sternotomy, those with prior sternotomy were more likely to be older, male, and present with more comorbidities and leads targeted for extraction. No statistical differences were identified in major and minor complication rates (=0.75, =0.41), clinical success rate (=0.26), and in-hospital mortality (=0.08). In patients with prior sternotomy, there were no instances of pericardial effusion after extraction. Prior sternotomy was not an independent predictor of clinical or procedural outcomes. No associations were elucidated after propensity-matched analysis.
Conclusions
In a large, single-center series, no differences in clinical or procedural outcomes were elucidated between patients with a history of sternotomy and those without. Patients with sternotomies before lead extraction who experienced vascular or cardiac perforations clinically presented with hemothoraces rather than pericardial effusions.



Circ Arrhythm Electrophysiol: 30 Aug 2019; 12:e007278
Tsang DC, Perez AA, Boyle TA, Carrillo RG
Circ Arrhythm Electrophysiol: 30 Aug 2019; 12:e007278 | PMID: 31522531
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Abstract

Atrial Fibrillation in Long QT Syndrome by Genotype.

Platonov PG, McNitt S, Polonsky B, Rosero SZ, Zareba W
Background
Long QT syndrome (LQTS) is caused by the abnormal function of ion channels, which may also affect atrial electrophysiology and be associated with the risk of atrial fibrillation (AF). However, large-scale studies of AF risk among patients with LQTS and its relation to LQTS manifestations are lacking. We aimed to assess the risk of AF and its relationship to the LQTS genotype and the long-term prognosis in patients with LQTS.
Methods
Genotype-positive patients with LQTS (784 LQT1, 746 LQT2, and 233 LQT3) were compared with 2043 genotype-negative family members. Information on the occurrence of AF was based on physician-reported ECG-verified events. Multivariate Cox proportional hazards regression analyses were performed for ages 0 to 60 and after 60 years (reflecting an early and late-onset of AF) to assess the risk of incident AF by genotype and the relationship of AF to the risk of cardiac events defined as syncope, documented torsades de pointes, and aborted cardiac arrest or sudden cardiac death.
Results
In patients followed from birth to 60 years of age, patients with LQT3 had an increased risk of AF compared with genotype-negative family members (hazard ratio=6.62; 95% CI, 2.04-21.49; <0.001), while neither LQT1 nor LQT2 demonstrated increased AF risk. After the age of 60 years, patients with LQT2 had significantly lower risk of AF compared with genotype-negative controls (hazard ratio=0.07; 95% CI, 0.01-0.53, =0.011). AF was a significant predictor of cardiac events in patients with LQT3 through the age of 60 (hazard ratio=5.38; 95% CI, 1.17-24.82; =0.031).
Conclusions
Our data demonstrate an increased risk of early age AF in patients with LQT3 and also indicate a protective effect of the LQT2 genotype in it\'s association with a decreased risk of AF after the age of 60.



Circ Arrhythm Electrophysiol: 29 Sep 2019; 12:e007213
Platonov PG, McNitt S, Polonsky B, Rosero SZ, Zareba W
Circ Arrhythm Electrophysiol: 29 Sep 2019; 12:e007213 | PMID: 31610692
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Abstract

Electrical Stimulation of the Greater Auricular Nerve to Reduce Postoperative Atrial Fibrillation.

Andreas M, Arzl P, Mitterbauer A, Ballarini NM, ... Laufer G, Wolzt M
Background
Postoperative atrial fibrillation (POAF) occurs in up to 40% of patients undergoing cardiac surgery. Invasive stimulation of the vagal nerve previously demonstrated a reduced risk of POAF. Therefore, we examined the antiarrhythmic and anti-inflammatory effects of noninvasive low-level transcutaneous electrical stimulation (LLTS) of the greater auricular nerve in a pilot trial including patients undergoing cardiac surgery.
Methods
Patients were randomized into a sham (n=20) or a treatment group (n=20) for LLTS. After cardiac surgery, electrodes were applied in the triangular fossa of the ear. Stimulation (amplitude 1 mA, frequency 1 Hz for 40 minutes, followed by a 20 minutes break) was performed for up to 2 weeks after cardiac surgery. Heart rhythm was recorded continuously using an ECG during the observation period. CRP (C-reactive protein) and IL (interleukin)-6 plasma concentrations were measured immediately after surgery as well as on day 2 and 7 postsurgery.
Results
Patients receiving LLTS had a significantly reduced occurrence of POAF (4 of 20) when compared with controls (11 of 20, =0.022) during a similar mean Holter recording period. The median duration of POAF was comparable between the treatment and the control group (878 [249; 1660] minutes versus 489 [148; 1775] minutes; =0.661). No effect of LLTS on CRP or IL-6 levels was detectable.
Conclusions
LLTS of the greater auricular nerve may be a potential therapy for POAF. We demonstrated the feasibility to conduct a randomized trial of neurostimulation as an outlay for a multisite clinical trial.



Circ Arrhythm Electrophysiol: 29 Sep 2019; 12:e007711
Andreas M, Arzl P, Mitterbauer A, Ballarini NM, ... Laufer G, Wolzt M
Circ Arrhythm Electrophysiol: 29 Sep 2019; 12:e007711 | PMID: 31597476
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Abstract

Catheter Ablation Versus Best Medical Therapy in Patients With Persistent Atrial Fibrillation and Congestive Heart Failure: The Randomized AMICA Trial.

Kuck KH, Merkely B, Zahn R, Arentz T, ... Kleemann T, Hindricks G
Background
Optimal treatment of patients with persistent atrial fibrillation (AF) and heart failure (HF) with reduced left ventricular ejection fraction (LVEF) and an indication for internal defibrillator therapy is controversial.
Methods
Patients with persistent/longstanding persistent AF and LVEF ≤35% were randomly allocated to catheter ablation of AF or best medical therapy (BMT). The primary study end point was the absolute increase in LVEF from baseline at 1 year. Secondary end points included 6-minute walk test, quality-of-life, and NT-proBNP (N-terminal pro-brain natriuretic peptide). Pulmonary vein isolation was the primary ablation approach; BMT comprised rate or rhythm control. All patients were discharged after index hospitalization with a cardioverter-defibrillator or cardiac resynchronization therapy defibrillator implanted. The study was terminated early for futility.
Results
Of 140 patients (65±8 years, 126 [90%] men) available for the end point analysis, 68 and 72 patients were assigned to ablation and BMT, respectively. At 1 year, LVEF had increased in ablation patients by 8.8% (95% CI, 5.8%-11.9%) and in BMT patients by 7.3% (4.3%-10.3%; =0.36). Sinus rhythm was recorded on 12-lead electrocardiograms at 1 year in 61/83 ablation patients (73.5%) and 42/84 BMT patients (50%). Device-recorded AF burden at 1 year was 0% or maximally 5% of the time in 28/39 ablation patients (72%) and 16/36 BMT patients (44%). There was no difference in secondary end point outcome between ablation patients and BMT patients.
Conclusions
The AMICA trial (Atrial Fibrillation Management in Congestive Heart Failure With Ablation) did not reveal any benefit of catheter ablation in patients with AF and advanced HF. This was mainly because of the fact that at 1 year, LVEF increased in ablation patients to a similar extent as in BMT patients. The effect of catheter ablation of AF in patients with HF may be affected by the extent of HF at baseline, with a rather limited ablation benefit in patients with seriously advanced HF.
Clinical trial registration
URL: https://www.clinicaltrials.gov. Unique identifier: NCT00652522.



Circ Arrhythm Electrophysiol: 29 Nov 2019; 12:e007731
Kuck KH, Merkely B, Zahn R, Arentz T, ... Kleemann T, Hindricks G
Circ Arrhythm Electrophysiol: 29 Nov 2019; 12:e007731 | PMID: 31760819
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Abstract

Effective Use of Percutaneous Stellate Ganglion Blockade in Patients With Electrical Storm.

Tian Y, Wittwer ED, Kapa S, McLeod CJ, ... Friedman PA, Cha YM
Background
Percutaneous stellate ganglion blockade (SGB) has been used for drug-refractory electrical storm due to ventricular arrhythmia (VA); however, the effects and long-term outcomes have not been well studied.
Methods
This study included 30 consecutive patients who had drug-refractory electrical storm and underwent percutaneous SGB between October 1, 2013, and March 31, 2018. Bupivacaine, alone or combined with lidocaine, was injected into the neck with good local anesthetic spread in the vicinity of the left stellate ganglion (n=15) or both stellate ganglia (n=15). Data were collected for patient clinical characteristics, immediate and long-term outcomes, and procedure-related complications.
Results
Clinical characteristics included age, 58±14 years; men, 73.3%; and left ventricular ejection fraction, 34±16%. At 24 hours, 60% of patients were free of VA. Patients whose VA was controlled had a lower hospital mortality rate than patients whose VA continued (5.6% versus 50.0%; =0.009). Implantable cardioverter-defibrillator interrogation showed a significant 92% reduction in VA episodes from 26±41 to 2±4 in the 72 hours after SGB (<0.001). Patients who died during the same hospitalization (n=7) were more likely to have ischemic cardiomyopathy (100% versus 43.5%; =0.03) and recurrent VA within 24 hours (85.7% versus 26.1%; =0.009). There were no procedure-related major complications.
Conclusions
SGB effectively attenuated electrical storm in more than half of patients without procedure-related complications. Percutaneous SGB may be considered for stabilizing ventricular rhythm in patients for whom other therapies have failed.



Circ Arrhythm Electrophysiol: 30 Aug 2019; 12:e007118
Tian Y, Wittwer ED, Kapa S, McLeod CJ, ... Friedman PA, Cha YM
Circ Arrhythm Electrophysiol: 30 Aug 2019; 12:e007118 | PMID: 31514529
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Abstract

Grid Mapping Catheter for Ventricular Tachycardia Ablation.

Okubo K, Frontera A, Bisceglia C, Paglino G, ... Calore F, Della Bella P
Background
A new grid mapping catheter (GMC)-allowing for bipolar recordings of the electrograms in each orthogonal direction-became available. The aim of the current study is to evaluate the utility of the GMC in creating substrate and ventricular tachycardia (VT) activation maps during VT ablation procedures.
Methods
From December 2017 to July 2018, 41 consecutive patients undergoing a VT ablation procedure using a GMC were studied. During the substrate mapping, 3 different maps were created using the 3 GMC bipolar configurations (along the spline, across the spline, HD wave solution); the low voltage area and late potential areas were compared. In case of inducible VTs, the GMC was used to create the VT activation maps focusing on the diastolic interval. The relation between diastolic activities during VT and substrate abnormality during sinus rhythm was also investigated.
Results
The median low-voltage area drawn by the HD wave configuration was 28.9 cm, 13% and 15% smaller than the low-voltage areas identified by the along and across configuration, respectively (33.1 and 33.9 cm; P<0.0001). The late potential areas obtained with the 3 GMC configuration did not differ (P>0.05). VT activation mappings using the GMC were performed in 40 VTs, visualizing the full diastolic pathway in 22 (55%) of them. While the latest late potential areas were included in VT diastolic pathway in 17 VTs, the other 6 VTs showed mismatching of them. Identifying the full diastolic pathway led to a higher ongoing VT termination rate during the ablation than in case of partial recordings (88% versus 45%; P=0.03); furthermore, in the former situation, the noninducibility of the targeted VTs was achieved in all cases.
Conclusions
The GMC is a useful tool for performing substrate and VT activation mappings during the VT ablation procedure, precisely identifying the low-voltage areas and quickly visualizing the diastolic pathways.



Circ Arrhythm Electrophysiol: 30 Aug 2019; 12:e007500
Okubo K, Frontera A, Bisceglia C, Paglino G, ... Calore F, Della Bella P
Circ Arrhythm Electrophysiol: 30 Aug 2019; 12:e007500 | PMID: 31500436
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Abstract

Catheter Ablation Versus Medical Therapy for Atrial Fibrillation.

Asad ZUA, Yousif A, Khan MS, Al-Khatib SM, Stavrakis S
Background
Despite the publication of several randomized clinical trials comparing catheter ablation (CA) with medical therapy (MT) in patients with atrial fibrillation (AF), the superiority of one strategy over another is still questioned by many. In this meta-analysis of randomized controlled trials, we compared the efficacy and safety of CA with MT for AF.
Methods
We systematically searched MEDLINE, EMBASE, and other online sources for randomized controlled trials of AF patients that compared CA with MT. The primary outcome was all-cause mortality. Secondary outcomes included cardiovascular hospitalizations and recurrence of atrial arrhythmia. Subgroup analyses stratified by the presence of heart failure with reduced ejection fraction, type of AF, age, and sex were performed. Risk ratios (RRs) with 95% CIs were calculated using a random effects model, and Mantel-Haenszel method was used to pool RR.
Results
Eighteen randomized controlled trials comprising 4464 patients (CA, n=2286; MT, n=2178) were included. CA resulted in a significant reduction in all-cause mortality (RR, 0.69; 95% CI, 0.54-0.88; P=0.003) that was driven by patients with AF and heart failure with reduced ejection fraction (RR, 0.52; 95% CI, 0.35-0.76; P=0.0009). CA resulted in significantly fewer cardiovascular hospitalizations (hazard ratio, 0.56; 95% CI, 0.39-0.81; P=0.002) and fewer recurrences of atrial arrhythmias (RR, 0.42; 95% CI, 0.33-0.53; P<0.00001). Subgroup analyses suggested that younger patients (age, <65 years) and men derived more benefit from CA compared with MT.
Conclusions
CA is associated with all-cause mortality benefit, that is driven by patients with AF and heart failure with reduced ejection fraction. CA reduces cardiovascular hospitalizations and recurrences of atrial arrhythmia for patients with AF. Younger patients and men appear to derive more benefit from CA.



Circ Arrhythm Electrophysiol: 30 Aug 2019; 12:e007414
Asad ZUA, Yousif A, Khan MS, Al-Khatib SM, Stavrakis S
Circ Arrhythm Electrophysiol: 30 Aug 2019; 12:e007414 | PMID: 31431051
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Abstract

Association of Total Reproductive Years With Incident Atrial Fibrillation, and Subsequent Ischemic Stroke in Women With Natural Menopause.

Yang S, Kwak S, Kwon S, Lee HJ, ... Kim YJ, Kim HK
Background
The association of lifetime exposure to endogenous sex hormone with incident atrial fibrillation (AF) and subsequent ischemic stroke has never been studied.
Methods
This study involved 4 638 299 natural postmenopausal waomen aged ≥40 years without prior history of AF and with national breast cancer check-up between January 1, 2009 and December 31, 2014. The primary end point was incident AF, and the secondary end point was subsequent ischemic stroke once AF has developed. Cox proportional hazard regression analysis was used to estimate the risk of end points.
Results
During the mean follow-up of 6.3 years, shorter total reproductive years (<30 years) were associated with 7% increased risk of AF after adjusting for confounding variables (adjusted hazard ratio [aHR], 1.07 [95% CI, 1.05-1.09]). Risk of AF declined progressively with every 5-yearly increment in total reproductive years (-for-trend <0.001). However, the prolonged (≥2 years) use of hormone replacement therapy after menopause was paradoxically associated with a 3% increase in AF risk (aHR, 1.03 [95% CI, 1.01-1.05]). For the secondary end point analysis, the risk of ischemic stroke after AF development significantly decreased with each 5-yearly increment in total reproductive years (with <30 years as reference; aHR, 0.93 [95% CI, 0.88-0.99] for 30-34 years; aHR, 0.84 [95% CI, 0.79-0.89] for 35-39 years; and aHR, 0.88 [95% CI, 0.80-0.97] for ≥40 years, -for-trend <0.001).
Conclusions
In women with natural menopause, shorter lifetime exposure to endogenous sex hormone, that is, shorter total reproductive years, was significantly associated with a higher risk of AF and subsequent ischemic stroke. Paradoxically, prolonged exogenous hormone replacement therapy increased the risk of incident AF.



Circ Arrhythm Electrophysiol: 30 Oct 2019; 12:e007428
Yang S, Kwak S, Kwon S, Lee HJ, ... Kim YJ, Kim HK
Circ Arrhythm Electrophysiol: 30 Oct 2019; 12:e007428 | PMID: 31661971
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Impact:
Abstract

Cardiomyocyte-Specific STIM1 (Stromal Interaction Molecule 1) Depletion in the Adult Heart Promotes the Development of Arrhythmogenic Discordant Alternans.

Cacheux M, Strauss B, Raad N, Ilkan Z, ... Hulot JS, Akar FG
Background
STIM1 (stromal interaction molecule 1) is a calcium (Ca) sensor that regulates cardiac hypertrophy by triggering store-operated Ca entry. Because STIM1 binding to phospholamban increases sarcoplasmic reticulum Ca load independent of store-operated Ca entry, we hypothesized that it controls electrophysiological function and arrhythmias in the adult heart.
Methods
Inducible myocyte-restricted STIM1-KD (STIM1 knockdown) was achieved in adult mice using an αMHC (α-myosin heavy chain)-MerCreMer system. Mechanical and electrophysiological properties were examined using echocardiography in vivo and optical action potential (AP) mapping ex vivo in tamoxifen-induced STIM1-Cre (STIM1-KD) and littermate controls for STIM1 (referred to as STIM1-Ctl) and for Cre without STIM deletion (referred to as Cre-Ctl).
Results
STIM1-KD mice (N=23) exhibited poor survival compared with STIM1-Ctl (N=22) and Cre-Ctl (N=11) with >50% mortality after only 8-days of cardiomyocyte-restricted STIM1-KD. STIM1-KD but not STIM1-Ctl or Cre-Ctl hearts exhibited a proclivity for arrhythmic behavior, ranging from frequent ectopy to pacing-induced ventricular tachycardia/ventricular fibrillation (VT/VF). Examination of the electrophysiological substrate revealed decreased conduction velocity and increased AP duration (APD) heterogeneity in STIM1-KD. These features, however, were comparable in VT/VF(+) and VT/VF(-) hearts. We also uncovered a marked increase in the magnitude of APD alternans during rapid pacing, and the emergence of a spatially discordant alternans profile in STIM1-KD hearts. Unlike conduction velocity slowing and APD heterogeneity, the magnitude of APD alternans was greater (by 80%, <0.05) in VT/VF(+) versus VT/VF(-) STIM1-KD hearts. Detailed phase mapping during the initial beats of VT/VF identified one or more rotors that were localized along the nodal line separating out-of-phase alternans regions.
Conclusions
In an adult murine model with inducible and myocyte-specific STIM1 depletion, we demonstrate for the first time the regulation of spatially discordant alternans by STIM1. Early mortality in STIM1-KD mice is likely related to enhanced susceptibility to VT/VF secondary to discordant APD alternans.



Circ Arrhythm Electrophysiol: 30 Oct 2019; 12:e007382
Cacheux M, Strauss B, Raad N, Ilkan Z, ... Hulot JS, Akar FG
Circ Arrhythm Electrophysiol: 30 Oct 2019; 12:e007382 | PMID: 31726860
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Abstract

Spatial Accuracy of a Clinically Established Noninvasive Electrocardiographic Imaging System for the Detection of Focal Activation in an Intact Porcine Model.

Hohmann S, Rettmann ME, Konishi H, Borenstein A, ... Newman LK, Packer DL
Background
Noninvasive electrocardiographic imaging (ECGi) is used clinically to map arrhythmias before ablation. Despite its clinical use, validation data regarding the accuracy of the system for the identification of arrhythmia foci is limited.
Methods
Nine pigs underwent closed-chest placement of endocardial fiducial markers, computed tomography, and pacing in all cardiac chambers with ECGi acquisition. Pacing location was reconstructed from biplane fluoroscopy and registered to the computed tomography using the fiducials. A blinded investigator predicted the pacing location from the ECGi data, and the distance to the true pacing catheter tip location was calculated.
Results
A total of 109 endocardial and 9 epicardial locations were paced in 9 pigs. ECGi predicted the correct chamber of origin in 85% of atrial and 92% of ventricular sites. Lateral locations were predicted in the correct chamber more often than septal locations (97% versus 79%, =0.01). Absolute distances in space between the true and predicted pacing locations were 20.7 (13.8-25.6) mm (median and [first-third] quartile). Distances were not significantly different across cardiac chambers.
Conclusions
The ECGi system is able to correctly identify the chamber of origin for focal activation in the vast majority of cases. Determination of the true site of origin is possible with sufficient accuracy with consideration of these error estimates.



Circ Arrhythm Electrophysiol: 30 Oct 2019; 12:e007570
Hohmann S, Rettmann ME, Konishi H, Borenstein A, ... Newman LK, Packer DL
Circ Arrhythm Electrophysiol: 30 Oct 2019; 12:e007570 | PMID: 31707808
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Impact:
Abstract

Effect of Direct Oral Anticoagulants, Warfarin, and Antiplatelet Agents on Risk of Device Pocket Hematoma: Combined Analysis of BRUISE CONTROL 1 and 2.

Essebag V, Healey JS, Joza J, Nery PB, ... Krahn AD, Birnie DH
Background
Oral anticoagulant use is common among patients undergoing pacemaker or defibrillator surgery. BRUISE CONTROL (Bridge or Continue Coumadin for Device Surgery Randomized Controlled Trial; NCT00800137) demonstrated that perioperative warfarin continuation reduced clinically significant hematomas (CSH) by 80% compared with heparin bridging (3.5% versus 16%). BRUISE-CONTROL-2 (NCT01675076) observed a similarly low risk of CSH when comparing continued versus interrupted direct oral anticoagulant (2.1% in both groups). Using patient level data from both trials, the current study aims to: (1) evaluate the effect of concomitant antiplatelet therapy on CSH, and (2) understand the relative risk of CSH in patients treated with direct oral anticoagulant versus continued warfarin.
Methods
We analyzed 1343 patients included in BRUISE-CONTROL-1 and BRUISE-CONTROL-2. The primary outcome for both trials was CSH. There were 408 patients identified as having continued either a single or dual antiplatelet agent at the time of device surgery.
Results
Antiplatelet use (versus nonuse) was associated with CSH in 9.8% versus 4.3% of patients (<0.001), and remained a strong independent predictor after multivariable adjustment (odds ratio, 1.965; 95% CI, 1.202-3.213; =0.0071). In multivariable analysis, adjusting for antiplatelet use, there was no significant difference in CSH observed between direct oral anticoagulant use compared with continued warfarin (odds ratio, 0.858; 95% CI, 0.375-1.963; =0.717).
Conclusions
Concomitant antiplatelet therapy doubled the risk of CSH during device surgery. No difference in CSH was found between direct oral anticoagulant versus continued warfarin. In anticoagulated patients undergoing elective or semi-urgent device surgery, the patient specific benefit/risk of holding an antiplatelet should be carefully considered.
Clinical trial registration
URL: https://www.clinicaltrials.gov. Unique identifiers: NCT00800137, NCT01675076.



Circ Arrhythm Electrophysiol: 29 Sep 2019; 12:e007545
Essebag V, Healey JS, Joza J, Nery PB, ... Krahn AD, Birnie DH
Circ Arrhythm Electrophysiol: 29 Sep 2019; 12:e007545 | PMID: 31610718
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Impact:
Abstract

Age and Sex Estimation Using Artificial Intelligence From Standard 12-Lead ECGs.

Attia ZI, Friedman PA, Noseworthy PA, Lopez-Jimenez F, ... Carter RE, Kapa S
Background
Sex and age have long been known to affect the ECG. Several biologic variables and anatomic factors may contribute to sex and age-related differences on the ECG. We hypothesized that a convolutional neural network (CNN) could be trained through a process called deep learning to predict a person\'s age and self-reported sex using only 12-lead ECG signals. We further hypothesized that discrepancies between CNN-predicted age and chronological age may serve as a physiological measure of health.
Methods
We trained CNNs using 10-second samples of 12-lead ECG signals from 499 727 patients to predict sex and age. The networks were tested on a separate cohort of 275 056 patients. Subsequently, 100 randomly selected patients with multiple ECGs over the course of decades were identified to assess within-individual accuracy of CNN age estimation.
Results
Of 275 056 patients tested, 52% were males and mean age was 58.6±16.2 years. For sex classification, the model obtained 90.4% classification accuracy with an area under the curve of 0.97 in the independent test data. Age was estimated as a continuous variable with an average error of 6.9±5.6 years (R-squared =0.7). Among 100 patients with multiple ECGs over the course of at least 2 decades of life, most patients (51%) had an average error between real age and CNN-predicted age of <7 years. Major factors seen among patients with a CNN-predicted age that exceeded chronologic age by >7 years included: low ejection fraction, hypertension, and coronary disease (P<0.01). In the 27% of patients where correlation was >0.8 between CNN-predicted and chronologic age, no incident events occurred over follow-up (33±12 years).
Conclusions
Applying artificial intelligence to the ECG allows prediction of patient sex and estimation of age. The ability of an artificial intelligence algorithm to determine physiological age, with further validation, may serve as a measure of overall health.



Circ Arrhythm Electrophysiol: 30 Aug 2019; 12:e007284
Attia ZI, Friedman PA, Noseworthy PA, Lopez-Jimenez F, ... Carter RE, Kapa S
Circ Arrhythm Electrophysiol: 30 Aug 2019; 12:e007284 | PMID: 31450977
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Abstract

Clinical and Electrophysiological Correlates of Incessant Ivabradine-Sensitive Atrial Tachycardia.

Banavalikar B, Shenthar J, Padmanabhan D, Valappil SP, ... Ghadei M, Ali M
Background
Incessant focal atrial tachycardia (FAT), if untreated, can lead to ventricular dysfunction and heart failure (tachycardia-induced cardiomyopathy). Drug therapy of FAT is often difficult and ineffective. The efficacy of ivabradine has not been systematically evaluated in the treatment of FAT.
Methods
The study group consisted of patients with incessant FAT (lasting >24 hours) and structurally normal hearts. Patients with ventricular dysfunction as a consequence of FAT were not excluded. All antiarrhythmic drugs were discontinued at least 5 half-lives before the initiation of ivabradine. Oral ivabradine (adults, 10 mg twice 12 hours apart; pediatric patients: 0.28 mg/kg in 2 divided doses) was initiated in the intensive care unit under continuous electrocardiographic monitoring. A positive response was defined as the termination of tachycardia with the restoration of sinus rhythm or suppression of the tachycardia to <100 beats per minute without termination within 12 hours of initiating ivabradine.
Results
Twenty-eight patients (mean age, 34.6±21.5 years; women, 60.7%) were included in the study. The most common symptom was palpitation (85.7%) followed by shortness of breath (25%). The mean atrial rate during tachycardia was 170±21 beats per minute, and the mean left ventricular ejection fraction was 54.7±14.3%. Overall, 18 (64.3%) patients responded within 6 hours of the first dose of ivabradine. Thirteen of 18 ivabradine responders subsequently underwent successful catheter ablation. FAT originating in the atrial appendages was a predictor of ivabradine response compared with those arising from other atrial sites (P=0.046).
Conclusions
Ivabradine-sensitive atrial tachycardia constitutes 64% of incessant FAT in patients without structural heart disease. Incessant FAT originating in the atrial appendages is more likely to respond to ivabradine than that arising from other atrial sites. Our findings implicate the funny current in the pathogenesis of FAT.



Circ Arrhythm Electrophysiol: 30 Jul 2019; 12:e007387
Banavalikar B, Shenthar J, Padmanabhan D, Valappil SP, ... Ghadei M, Ali M
Circ Arrhythm Electrophysiol: 30 Jul 2019; 12:e007387 | PMID: 31345093
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Abstract

Variable Presentations and Ablation Sites for Manifest Nodoventricular/Nodofascicular Fibers.

Nazer B, Walters TE, Dewland TA, Naniwadekar A, ... Gerstenfeld EP, Scheinman MM
Background
Nodofascicular and nodoventricular (NFV) accessory pathways connect the atrioventricular node and the Purkinje system or ventricular myocardium, respectively. Concealed NFV pathways participate as the retrograde limb of supraventricular tachycardia (SVT). Manifest NFV pathways can comprise the anterograde limb of wide-complex SVT but are quite rare. The purpose of this report is to highlight the electrophysiological properties and sites of ablation for manifest NFV pathways.
Methods
Eight patients underwent electrophysiology studies for wide-complex tachycardia (3), for narrow-complex tachycardia (1), and preexcitation (4).
Results
NFV was an integral part of the SVT circuit in 3 patients. Cases 1 to 2 were wide-complex tachycardia because of manifest NFV SVT. Case 3 was a bidirectional NFV that conducted retrograde during concealed NFV SVT and anterograde causing preexcitation during atrial pacing. NFV was a bystander during atrioventricular node re-entrant tachycardia, atrial fibrillation, atrial flutter, and orthodromic atrioventricular re-entrant tachycardia in 4 cases and caused only preexcitation in 1. Successful NFV ablation was achieved empirically in the slow pathway region in 1 case. In 5 cases, the ventricular insertion was mapped to the slow pathway region (2 cases) or septal right ventricle (3 cases). The NFV was not mapped in cases 5 and 7 because of its bystander role. QRS morphology of preexcitation predicted the right ventricle insertion sites in 4 of the 5 cases in which it was mapped. During follow-up, 1 patient noted recurrent palpitations but no documented SVT.
Conclusions
Manifest NFV may be critical for wide-complex tachycardia/manifest NFV SVT, act as the retrograde limb for narrow-complex tachycardia/concealed NFV SVT, or cause bystander preexcitation. Ablation should initially target the slow pathway region, with mapping of the right ventricle insertion site if slow pathway ablation is not successful. The QRS morphology of maximal preexcitation may be helpful in predicting successful right ventricle ablation site.



Circ Arrhythm Electrophysiol: 30 Aug 2019; 12:e007337
Nazer B, Walters TE, Dewland TA, Naniwadekar A, ... Gerstenfeld EP, Scheinman MM
Circ Arrhythm Electrophysiol: 30 Aug 2019; 12:e007337 | PMID: 31505948
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Impact:
Abstract

Impact of Spacing and Orientation on the Scar Threshold With a High-Density Grid Catheter.

Takigawa M, Relan J, Kitamura T, Martin CA, ... Sacher F, Jaïs P
Background
Multipolar catheters are increasingly used for high-density mapping. However, the threshold to define scar areas has not been well described for each configuration. We sought to elucidate the impact of bipolar spacing and orientation on the optimal threshold to match magnetic resonance imaging-defined scar.
Method
The HD-Grid catheter uniquely allows for different spatially stable bipolar configurations to be tested. We analyzed the electrograms with settings of HD-16 (3 mm spacing in both along and across bipoles) and HD-32 (1 mm spacing in along bipoles and 3 mm spacing in across bipoles) and determined the optimal cutoff for scar detection in 6 infarcted sheep.
Results
From 456 total acquisition sites (mean 76±12 per case), 14 750 points with the HD-16 and 32286 points with the HD-32 configuration for bipolar electrograms were analyzed. For bipolar voltages, the optimal cutoff value to detect the magnetic resonance imaging-defined scar based on the Youden\'s Index, and the area under the receiver operating characteristic curve (AUROC) differed depending on the spacing and orientation of bipoles; across 0.84 mV (AUROC, 0.920; 95% CI, 0.911-0.928), along 0.76 mV (AUROC, 0.903; 95% CI, 0.893-0.912), north-east direction 0.95 mV (AUROC, 0.923; 95% CI, 0.913-0.932), and south-east direction, 0.87 mV (AUROC, 0.906; 95% CI, 0.895-0.917) in HD-16; and across 0.83 mV (AUROC, 0.917; 95% CI, 0.911-0.924), along 0.46 mV (AUROC, 0.890; 95% CI, 0.883-0.897), north-east direction 0.89 mV (AUROC, 0.923; 95% CI, 0.917-0.929), and south-east direction 0.83 mV (AUROC, 0.913; 95% CI, 0.906-0.920) in HD-32. Significant differences in AUROC were seen between HD-16 along versus across (P=0.002), HD-16 north-east direction versus south-east direction (P=0.01), HD-32 north-east direction versus south-east direction (P<0.0001), and HD-16 along versus HD-32 along (P=0.006). The AUROC was significantly larger (P<0.01) when only the best points on each given site were selected for analysis, compared with when all points were used.
Conclusions
Spacing and orientation of bipoles impacts the accuracy of scar detection. Optimal threshold specific to each bipolar configuration should be determined. Selecting one best voltage point among multiple points projected on the same surface is also critical on the Ensite-system to increase the accuracy of scar-mapping.



Circ Arrhythm Electrophysiol: 30 Aug 2019; 12:e007158
Takigawa M, Relan J, Kitamura T, Martin CA, ... Sacher F, Jaïs P
Circ Arrhythm Electrophysiol: 30 Aug 2019; 12:e007158 | PMID: 31446771
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Abstract

Avoidance of Vagal Response During Circumferential Pulmonary Vein Isolation: Effect of Initiating Isolation From Right Anterior Ganglionated Plexi.

Hu F, Zheng L, Liu S, Shen L, ... Fan X, Yao Y
Background
Circumferential pulmonary vein isolation (CPVI) often cause unavoidable vagal reflexes during procedure due to the coincidental modification of ganglionated plexus which are located on pulmonary vein (PV) antrum. The right anterior ganglionated plexi (RAGP) which located at superoanterior area of right superior PV antrum is an essential station to regulate the cardiac autonomic nerve activities and is easily coincidentally ablated during CPVI. The aim of this study is to assess the effect of RAGP ablation on vagal response (VR) during CPVI.
Methods
A total of 80 patients with paroxysmal atrial fibrillation who underwent the first time CPVI were prospectively enrolled and randomly assigned to 2 groups: group A (n=40), CPVI started with right PVs at RAGP site; group B (n=40): CPVI started with left PVs first, and the last ablation site is RAGP. Electrophysiological parameters include basal cycle length, A-H interval, H-V interval, sinus node recovery time, and atrioventricular node Wenckebach point were recorded before and after CPVI procedure.
Results
During CPVI, the positive VR were only observed on 1 patient in group A and 25 patients in group B (<0.001). A total of 21 patients with positive VR in group B needed for temporary ventricular pacing during procedure, while the only patient with positive VR in group A did not need for temporary ventricular pacing (<0.001). Compared with baseline, basal cycle length, sinus node recovery time, and atrioventricular node Wenckebach point were decreased significantly after CPVI procedure in both groups (all <0.05) and without differences between 2 groups.
Conclusions
Circumferential PV isolation initiated from RAGP could effectively inhibit VR occurrence and significantly increase heart rate during procedure.



Circ Arrhythm Electrophysiol: 29 Nov 2019; 12:e007811
Hu F, Zheng L, Liu S, Shen L, ... Fan X, Yao Y
Circ Arrhythm Electrophysiol: 29 Nov 2019; 12:e007811 | PMID: 31760820
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Impact:
Abstract

Does Ventricular Tachycardia Ablation Targeting Local Abnormal Ventricular Activity Elimination Reduce Ventricular Fibrillation Incidence?

Kitamura T, Maury P, Lam A, Sacher F, ... Haissaguerre M, Jais P
Background
Various strategies for ablation of ventricular tachycardia (VT) have been described, but their impact on ventricular fibrillation (VF) is largely unknown. The aim of our study was to assess the effect of substrate-based VT ablation targeting local abnormal ventricular activity (LAVA) on recurrent VF events in patients with structural heart disease.
Methods
A retrospective 2-center study was performed on patients with structural heart disease and both VT and VF, with incident VT ablation procedures targeting LAVAs. Generalized estimating equations with a Poisson loglinear model were used to assess the impact of catheter ablation on VF episodes. The change in VF events before and after catheter ablation was compared with matched controls without ablation.
Results
From a total of 686 patients with an incident VT ablation procedure targeting LAVAs, 21 patients (age, 57±14 years; left ventricular ejection fraction, 30±10%) had both VT and VF and met inclusion criteria. A total of 80 VF events were recorded in the implantable cardioverter-defibrillator logs the 6 months preceding ablation. Complete and partial LAVA elimination was achieved in 11 (52%) and 10 (48%) patients, respectively. Catheter ablation was associated with a highly significant reduction in VF recurrences (<0.0001), which were limited to 3 (14%) patients at 6 months. The total number of VF events thereby decreased from 80 to 3, from a median of 1.0 (range, 1-29) to 0.0 (range, 0-1) in the 6 months before and after ablation, respectively. The reduction in VF events was significantly greater in patients with catheter ablation compared with 21 matched controls during 6-month periods following and preceding a baseline assessment (Poisson β-coefficient, 1.39; =0.0003).
Conclusions
Substrate-guided VT ablation targeting LAVAs may be associated with a significant reduction in recurrent VF, suggesting that VT and VF share overlapping arrhythmogenic substrates in patients with structural heart disease.



Circ Arrhythm Electrophysiol: 29 Nov 2019; 12:e006857
Kitamura T, Maury P, Lam A, Sacher F, ... Haissaguerre M, Jais P
Circ Arrhythm Electrophysiol: 29 Nov 2019; 12:e006857 | PMID: 31760821
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Impact:
Abstract

Genetic Ablation of TASK-1 (Tandem of P Domains in a Weak Inward Rectifying K Channel-Related Acid-Sensitive K Channel-1) (K3.1) K Channels Suppresses Atrial Fibrillation and Prevents Electrical Remodeling.

Schmidt C, Wiedmann F, Beyersdorf C, Zhao Z, ... Katus HA, Thomas D
Background
Despite an increasing understanding of atrial fibrillation (AF) pathophysiology, translation into mechanism-based treatment options is lacking. In atrial cardiomyocytes of patients with chronic AF, expression, and function of tandem of P domains in a weak inward rectifying TASK-1 (K channel-related acid-sensitive K channel-1) (K3.1) atrial-specific 2-pore domain potassium channels is enhanced, resulting in action potential duration shortening. TASK-1 channel inhibition prevents action potential duration shortening to maintain values observed among sinus rhythm subjects. The present preclinical study used a porcine AF model to evaluate the antiarrhythmic efficacy of TASK-1 inhibition by adeno-associated viral anti-TASK-1-siRNA (small interfering RNA) gene transfer.
Methods
AF was induced in domestic pigs by atrial burst stimulation via implanted pacemakers. Adeno-associated viral vectors carrying anti-TASK-1-siRNA were injected into both atria to suppress TASK-1 channel expression. After the 14-day follow-up period, porcine cardiomyocytes were isolated from right and left atrium, followed by electrophysiological and molecular characterization.
Results
AF was associated with increased TASK-1 transcript, protein and ion current levels leading to shortened action potential duration in atrial cardiomyocytes compared to sinus rhythm controls, similar to previous findings in humans. Anti-TASK-1 adeno-associated viral application significantly reduced AF burden in comparison to untreated AF pigs. Antiarrhythmic effects of anti-TASK-1-siRNA were associated with reduction of TASK-1 currents and prolongation of action potential durations in atrial cardiomyocytes to sinus rhythm values. Conclusions Adeno-associated viral-based anti-TASK-1 gene therapy suppressed AF and corrected cellular electrophysiological remodeling in a porcine model of AF. Suppression of AF through selective reduction of TASK-1 currents represents a new option for antiarrhythmic therapy.



Circ Arrhythm Electrophysiol: 30 Aug 2019; 12:e007465
Schmidt C, Wiedmann F, Beyersdorf C, Zhao Z, ... Katus HA, Thomas D
Circ Arrhythm Electrophysiol: 30 Aug 2019; 12:e007465 | PMID: 31514528
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Impact:
Abstract

Eccentric Activation Patterns in the Left Ventricular Outflow Tract during Idiopathic Ventricular Arrhythmias Originating From the Left Ventricular Summit.

Yamada T, Kumar V, Yoshida N, Doppalapudi H
Background
Idiopathic ventricular arrhythmias (VAs) originating from the left ventricular summit (LVS) can be ablated from the great cardiac vein and remote endocardial sites. The ablation sites are determined by mapping in the great cardiac vein and left ventricular outflow tract. This study investigated whether that mapping could accurately predict the sites of LVS-VA origins.
Methods
We studied 26 consecutive patients with idiopathic LVS-VA origins that were identified in the basal and apical LVS in 15 and 11 patients, respectively.
Results
Radiofrequency catheter ablation of the apical LVS-VAs was successful in the great cardiac vein in 9 patients and in the apical LV outflow tract in 2. That of the basal LVS-VAs was successful in the aortomitral continuity in 9 patients, at the junction of the left and right coronary cusps in 4, and in the left coronary cusp in 2. Three apical LVS-VAs exhibited an eccentric endocardial activation pattern that was from the basal to apical LV outflow tract. In 11 basal LVS-VAs, the activation pattern was eccentric because the ventricular activation within the great cardiac vein in the apical LVS was earlier than that in the basal LV outflow tract. In 2 basal LVS-VAs, the activation pattern was eccentric because a relatively early ventricular activation was recorded at multiple sites away from the successful ablation site.
Conclusions
Eccentric activation patterns often occurred during idiopathic LVS-VAs, which could mislead the catheter ablation of those VAs. Understanding such eccentric activation patterns was suggested to be able to improve the outcomes of the catheter ablation of those VAs by the anatomic approach.



Circ Arrhythm Electrophysiol: 30 Jul 2019; 12:e007419
Yamada T, Kumar V, Yoshida N, Doppalapudi H
Circ Arrhythm Electrophysiol: 30 Jul 2019; 12:e007419 | PMID: 31401854
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Impact:
Abstract

Wavefront Field Mapping Reveals a Physiologic Network Between Drivers Where Ablation Terminates Atrial Fibrillation.

Leef G, Shenasa F, Bhatia NK, Rogers AJ, ... Wang PJ, Narayan SM
Background
Localized drivers are proposed mechanisms for persistent atrial fibrillation (AF) from optical mapping of human atria and clinical studies of AF, yet are controversial because drivers fluctuate and ablating them may not terminate AF. We used wavefront field mapping to test the hypothesis that AF drivers, if concurrent, may interact to produce fluctuating areas of control to explain their appearance/disappearance and acute impact of ablation.
Methods
We recruited 54 patients from an international registry in whom persistent AF terminated by targeted ablation. Unipolar AF electrograms were analyzed from 64-pole baskets to reconstruct activation times, map propagation vectors each 20 ms, and create nonproprietary phase maps.
Results
Each patient (63.6±8.5 years, 29.6% women) showed 4.0±2.1 spatially anchored rotational or focal sites in AF in 3 patterns. First, a single (type I; n=7) or, second, paired chiral-antichiral (type II; n=5) rotational drivers controlled most of the atrial area. Ablation of 1 to 2 large drivers terminated all cases of types I or II AF. Third, interaction of 3 to 5 drivers (type III; n=42) with changing areas of control. Targeted ablation at driver centers terminated AF and required more ablation in types III versus I (P=0.02 in left atrium).
Conclusions
Wavefront field mapping of persistent AF reveals a pathophysiologic network of a small number of spatially anchored rotational and focal sites, which interact, fluctuate, and control varying areas. Future work should define whether AF drivers that control larger atrial areas are attractive targets for ablation.



Circ Arrhythm Electrophysiol: 30 Jul 2019; 12:e006835
Leef G, Shenasa F, Bhatia NK, Rogers AJ, ... Wang PJ, Narayan SM
Circ Arrhythm Electrophysiol: 30 Jul 2019; 12:e006835 | PMID: 31352796
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Impact:
Abstract

Endovascular Occlusion Balloon for Treatment of Superior Vena Cava Tears During Transvenous Lead Extraction.

Azarrafiy R, Tsang DC, Wilkoff BL, Carrillo RG
Background
Superior vena cava (SVC) tears are one of the most lethal complications in transvenous lead extraction. An endovascular balloon can occlude the SVC in the event of a laceration, preventing blood loss and offering a more controlled surgical field for repair. An early study demonstrated that proper use of this device is associated with reduced mortality. Thereafter, high-volume extractors at the Eleventh Annual Lead Management Symposium developed a best practice protocol for the endovascular balloon.
Methods
We collected data on adverse events in lead extraction from July 1, 2016, to July 31, 2018. Data were prospectively collected from both a US Food and Drug Administration-maintained database and physician reports of adverse events as they occurred. We gathered case details directly from extracting physicians. Confirmed SVC tears were analyzed for patient demographics, case details, and index hospitalization mortality.
Results
From July 1, 2016, to July 31, 2018, 116 confirmed SVC events were identified, of which 44.0% involved proper balloon use and 56.0% involved no use or improper use. When an endovascular balloon was properly used, 45 of 51 patients (88.2%) survived in comparison to 37 of 65 patients (56.9%) when a balloon was not used or improperly used (P=0.0002). Furthermore, multivariate regression modeling found that proper balloon deployment was an independent, negative predictor of in-hospital mortality for patients who experienced an SVC laceration (odds ratio, 0.13; 95% CI, 0.04-0.40; P<0.001).
Conclusions
From July 1, 2016, through July 31, 2018, patients undergoing lead extraction were more likely to survive SVC tears when treatment included an endovascular balloon.



Circ Arrhythm Electrophysiol: 30 Jul 2019; 12:e007266
Azarrafiy R, Tsang DC, Wilkoff BL, Carrillo RG
Circ Arrhythm Electrophysiol: 30 Jul 2019; 12:e007266 | PMID: 31401856
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Impact:
Abstract

Evaluation After Sudden Death in the Young.

Gray B, Ackerman MJ, Semsarian C, Behr ER

Sudden cardiac death is defined as a death occurring usually within an hour of onset of symptoms, arising from an underlying cardiac disease. Sudden cardiac death is a complication of a number of cardiovascular diseases and is often unexpected. In individuals aged <35 years, unexplained sudden cardiac death is the most common presentation. A significant proportion of sudden cardiac death in the young (≤35 years) events may be precipitated by underlying inherited cardiac conditions, including both heritable cardiomyopathies and inherited arrhythmia syndromes (also known as cardiac channelopathies). Tragically, sudden death may be the first manifestation of the disease in a family and, therefore, clinical and genetic evaluation of surviving family members forms a key role in diagnosing the underlying inherited cardiac condition in the family. This is particularly relevant when considering that most inherited cardiac conditions are inherited in an autosomal dominant manner meaning that surviving family members have a 50% chance of inheriting the same disease substrate. This review will outline the underlying causes of sudden cardiac death in the young and outline our universal approach to familial evaluation following a young person\'s sudden death.



Circ Arrhythm Electrophysiol: 30 Jul 2019; 12:e007453
Gray B, Ackerman MJ, Semsarian C, Behr ER
Circ Arrhythm Electrophysiol: 30 Jul 2019; 12:e007453 | PMID: 31422686
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Impact:
Abstract

Ripple-AT Study.

Luther V, Agarwal S, Chow A, Koa-Wing M, ... Linton NWF, Kanagaratnam P
Background
Ripple mapping (RM) is an alternative approach to activation mapping of atrial tachycardia (AT) that avoids electrogram annotation. We tested whether RM is superior to conventional annotation based local activation time (LAT) mapping for AT diagnosis in a randomized and multicenter study.
Methods
Patients with AT were randomized to either RM or LAT mapping using the CARTO3v4 CONFIDENSE system. Operators determined the diagnosis using the assigned 3D mapping arm alone, before being permitted a single confirmatory entrainment manuever if needed. A planned ablation lesion set was defined. The primary end point was AT termination with delivery of the planned ablation lesion set. The inability to terminate AT with this first lesion set, the use of more than one entrainment manuever, or the need to crossover to the other mapping arm was defined as failure to achieve the primary end point.
Results
One hundred five patients from 7 centers were recruited with 22 patients excluded due to premature AT termination, noninducibility or left atrial appendage thrombus. Eighty-three patients (pts; RM=42, LAT=41) completed mapping and ablation within the 2 groups of similar characteristics (RM versus LAT: prior ablation or cardiac surgery n=35 [83%] versus n=35 [85%], P=0.80). The primary end point occurred in 38/42 pts (90%) in the RM group and 29/41pts (71%) in the LAT group (P=0.045). This was achieved without any entrainment in 31/42 pts (74%) with RM and 18/41 pts (44%) with LAT (P=0.01). Of those patients who failed to achieve the primary end point, AT termination was achieved in 9/12 pts (75%) in the LAT group following crossover to RM with entrainment, but 0/4 pts (0%) in the RM group crossing over to LAT mapping with entrainment (P=0.04).
Conclusions
RM is superior to LAT mapping on the CARTO3v4 CONFIDENSE system in guiding ablation to terminate AT with the first lesion set and with reduced entrainment to assist diagnosis.
Clinical trials registration
https://www.clinicaltrials.gov. Unique identifier: NCT02451995.



Circ Arrhythm Electrophysiol: 30 Jul 2019; 12:e007394
Luther V, Agarwal S, Chow A, Koa-Wing M, ... Linton NWF, Kanagaratnam P
Circ Arrhythm Electrophysiol: 30 Jul 2019; 12:e007394 | PMID: 31394921
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Impact:
Abstract

Feasibility, Safety, and Efficacy of Posterior Wall Isolation During Atrial Fibrillation Ablation.

Thiyagarajah A, Kadhim K, Lau DH, Emami M, ... Mahajan R, Sanders P
Background
The posterior left atrium is an arrhythmogenic substrate that contributes to the initiation and maintenance of atrial fibrillation (AF); however, the feasibility, safety, and efficacy of posterior wall isolation (PWI) as an AF ablation strategy has not been widely reported.
Methods
We undertook a systematic review and meta-analysis of studies performing PWI to assess (1) acute procedural success including the ability to achieve PWI and the number of procedure-related complications, (2) Long-term, clinical success including rates of arrhythmia recurrence and posterior wall reconnection, and (3) The efficacy of PWI compared with pulmonary vein isolation on preventing arrhythmia recurrence. MEDLINE, EMBASE, and Web of Science databases were searched in May 2018 to retrieve relevant studies. Results were pooled using a random effects model.
Results
Seventeen studies (13 box isolation, 3 single ring isolation, and 1 debulking ablation) comprising 1643 patients (31.3% paroxysmal AF, left atrial diameter 41±3.1 mm) were included in the final analysis. In studies focusing specifically on PWI, the acute procedural success rate for achieving PWI was 94.1% (95% CI, 87.2%-99.3%). Single-procedure 12-month freedom from atrial arrhythmia was 65.3% (95% CI, 57.7%-73.9%) overall and 61.9% (54.2%-70.8%) for persistent AF. Randomized control trials comparing PWI to pulmonary vein isolation (3 studies, 444 patients) yielded conflicting results and could not confirm an incremental benefit to PWI. Fifteen major complications (0.1%), including 2 atrio-esophageal fistulas, were reported.
Conclusions
PWI as an end point of AF ablation can be achieved in a large proportion of cases with good rates of 12-month freedom from atrial arrhythmia. Although the procedure-related complication rate is low, it did not eliminate the risk of atrio-esophageal fistula. Registration: URL: http://www.crd.york.ac.uk/prospero. PROSPERO registration number: CRD42018107212.



Circ Arrhythm Electrophysiol: 30 Jul 2019; 12:e007005
Thiyagarajah A, Kadhim K, Lau DH, Emami M, ... Mahajan R, Sanders P
Circ Arrhythm Electrophysiol: 30 Jul 2019; 12:e007005 | PMID: 31401853
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Impact:
Abstract

In Vivo Restoration of Myocardial Conduction With Carbon Nanotube Fibers.

McCauley MD, Vitale F, Yan JS, Young CC, ... Razavi M, Pasquali M
Background
Impaired myocardial conduction is the underlying mechanism for re-entrant arrhythmias. Carbon nanotube fibers (CNTfs) combine the mechanical properties of suture materials with the conductive properties of metals and may form a restorative solution to impaired myocardial conduction.
Methods
Acute open chest electrophysiology studies were performed in sheep (n=3). Radiofrequency ablation was used to create epicardial conduction delay after which CNTf and then silk suture controls were applied. CNTfs were surgically sewn across the right atrioventricular junction in rodents, and acute (n=3) and chronic (4-week, n=6) electrophysiology studies were performed. Rodent toxicity studies (n=10) were performed. Electrical analysis of the CNTf-myocardial interface was performed.
Results
In all cases, the large animal studies demonstrated improvement in conduction velocity using CNTf. The acute rodent model demonstrated ventricular preexcitation during sinus rhythm. All chronic cases demonstrated resumption of atrioventricular conduction, but these required atrial pacing. There was no gross or histopathologic evidence of toxicity. Ex vivo studies demonstrated contact impedance significantly lower than platinum iridium.
Conclusions
Here, we show that in sheep, CNTfs sewn across epicardial scar acutely improve conduction. In addition, CNTf maintain conduction for 1 month after atrioventricular nodal ablation in the absence of inflammatory or toxic responses in rats but only in the paced condition. The CNTf/myocardial interface has such low impedance that CNTf can facilitate local, downstream myocardial activation. CNTf are conductive, biocompatible materials that restore electrical conduction in diseased myocardium, offering potential long-term restorative solutions in pathologies interrupting efficient electrical transduction in electrically excitable tissues.



Circ Arrhythm Electrophysiol: 30 Jul 2019; 12:e007256
McCauley MD, Vitale F, Yan JS, Young CC, ... Razavi M, Pasquali M
Circ Arrhythm Electrophysiol: 30 Jul 2019; 12:e007256 | PMID: 31401852
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Abstract

Targeting Nonpulmonary Vein Sources in Persistent Atrial Fibrillation Identified by Noncontact Charge Density Mapping.

Willems S, Verma A, Betts TR, Murray S, ... Meyer C, Grace A

Background Identification and elimination of nonpulmonary vein targets may improve clinical outcomes in patients with persistent atrial fibrillation (AF). We report on the use of a novel, noncontact imaging and mapping system that uses ultrasound to reconstruct atrial chamber anatomy and measures timing and density of dipolar, ionic activation (ie, charge density) across the myocardium to guide ablation of atrial arrhythmias. Methods The prospective, nonrandomized UNCOVER AF trial (Utilizing Novel Dipole Density Capabilities to Objectively Visualize the Etiology of Rhythms in Atrial Fibrillation) was conducted at 13 centers across Europe and Canada. Patients with persistent AF (>7 days, <1 year) aged 18 to 80 years, scheduled for de novo catheter ablation, were eligible. Before pulmonary vein isolation, AF was mapped and then iteratively remapped to guide each subsequent ablation of charge density-identified targets. AF recurrence was evaluated at 3, 6, 9, and 12 months using continuous 24-hour ECG monitors. The primary effectiveness outcome was freedom from AF >30 seconds at 12 months for a single procedure with a secondary outcome being acute procedural efficacy. The primary safety outcome was freedom from device/procedure-related major adverse events. Results Between October 2016 and April 2017, 129 patients were enrolled, and 127 underwent mapping and catheter ablation. Acute procedural efficacy was demonstrated in 125 patients (98%). At 12 months, single procedure freedom from AF on or off antiarrhythmic drugs was 72.5% (95% CI, 63.9%-80.3%). After 1 or 2 procedures, freedom from AF was 93.2% (95% CI, 87.1%-97.0%). A total of 29 (23%) retreatments because of arrhythmia recurrence were performed with average time from index procedure to first retreatment being 7 months. The primary safety outcome was 98% with no device-related major adverse events reported. Conclusions This novel ultrasound imaging and charge density mapping system safely guided ablation of nonpulmonary vein targets in persistent AF patients with 73% single procedure and 93% second procedure freedom from AF at 12 months. Clinical Trial registration URL: https://www.clinicaltrials.gov . Unique identifier: NCT02825992 EU/NCT02462980 CN.



Circ Arrhythm Electrophysiol: 29 Jun 2019; 12:e007233
Willems S, Verma A, Betts TR, Murray S, ... Meyer C, Grace A
Circ Arrhythm Electrophysiol: 29 Jun 2019; 12:e007233 | PMID: 31242746
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Abstract

Late Gadolinium Enhancement Magnetic Resonance Imaging Guided Treatment of Post-Atrial Fibrillation Ablation Recurrent Arrhythmia.

Fochler F, Yamaguchi T, Kheirkahan M, Kholmovski EG, Morris AK, Marrouche NF
Background
Macroreentrant atrial tachycardia (AT) accounts for 40% to 60% of recurrent atrial arrhythmias after atrial fibrillation (AF) ablation. To describe late gadolinium enhancement magnetic resonance imaging (LGE-MRI)-detected scar-based dechanneling as new ablation strategy to treat ATs after AF ablation.
Methods
Data from 102 patients who underwent initial AF ablation and repeat ablation for recurrent atrial arrhythmia within 1-year follow-up were analyzed. All patients underwent LGE-MRI before initial and repeat ablation. Depending on the recurrent rhythm, patients with AF and AT recurrence were assigned to group 1 or 2, respectively. Group 1 underwent fibrosis homogenization as second procedure. Group 2 underwent LGE-MRI-detected scar-based dechanneling. Both groups underwent reisolation of pulmonary veins if necessary.
Results
Forty-six patients (45%) presented with AF, and 56 patients (55%) presented with AT recurrence during follow-up after initial ablation. In the first 25 patients from group 2, the AT was electroanatomically mapped, and a critical isthmus was defined. It was found that those isthmi were located in the regions with nontransmural scarring detected by LGE-MRI. In the last 31 patients from group 2, an empirical LGE-MRI-based dechanneling was performed solely based on the LGE-MRI results. During 1-year follow-up after second ablation, 67% patients in group 1 and 64% patients in group 2 were free from recurrence (log-rank, P=1.000). In group 2, 64% in the electroanatomically guided and 65% in the LGE-MRI dechanneling group were free from recurrence (log-rank, P=0.900).
Conclusions
Anatomic targeting of LGE-MRI-detected gaps and superficial atrial scar is feasible and effective to treat recurrent arrhythmias post-AF ablation. Homogenization of existing scar is the appropriate treatment for recurrent AF, whereas dechanneling of existing isthmi seems the right approach for patients recurring with AT.



Circ Arrhythm Electrophysiol: 30 Jul 2019; 12:e007174
Fochler F, Yamaguchi T, Kheirkahan M, Kholmovski EG, Morris AK, Marrouche NF
Circ Arrhythm Electrophysiol: 30 Jul 2019; 12:e007174 | PMID: 31422685
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Abstract

Impact of Bariatric Surgery on Atrial Fibrillation Type.

Donnellan E, Wazni O, Elshazly M, Kanj M, ... Jaber W, Saliba W

- Obesity is an independent risk factor for atrial fibrillation (AF) and is associated with a higher AF burden. Recently, weight loss has been found to be associated with a significant reversal in AF type. Bariatric surgery (BS) is associated with reductions in inflammation, left atrial and ventricular remodeling, sleep apnea, blood pressure and improved glycemic control, all of which may reduce AF burden. In this study we sought to determine the impact of BS on AF type.- We studied AF type prior to and following BS in 220 morbidly obese patients (BMI Ȧ5; 40 kg/m). All patients underwent extended outpatient cardiac rhythm monitoring within 12 months of BS and at least 1 year after BS.- There was a significant reduction in BMI following BS from 49.7±9 to 37.2±9 kg/m. Weight loss was greatest in the gastric bypass group with a mean % weight loss of 25% compared to 19% in patients who underwent sleeve gastrectomy and 16% following gastric banding (p<0.0001). Significant reductions in CRP, NT-proBNP, HbA1C and systolic blood pressure were observed in all 3 groups. Reversal of AF type occurred in 71% of patients following gastric bypass, 56% of patients who underwent sleeve gastrectomy and 50% of patients following gastric banding (p=0.004). On Cox proportional hazards analyses, % weight loss was significantly associated with AF reversal (p=0.0002).- Bariatric surgery is associated with significant reductions in weight, inflammatory markers, blood pressure and AF type and the beneficial effects appear to be greatest in those undergoing gastric bypass surgery. This study further exemplifies the importance of weight loss and risk factor modification in AF management.



Circ Arrhythm Electrophysiol: 14 Jan 2020; epub ahead of print
Donnellan E, Wazni O, Elshazly M, Kanj M, ... Jaber W, Saliba W
Circ Arrhythm Electrophysiol: 14 Jan 2020; epub ahead of print | PMID: 31940441
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Abstract

Plasticizer Interaction With the Heart.

Jaimes R, McCullough D, Siegel B, Swift L, ... Tereshchenko LG, Posnack NG
Background
Phthalates are used as plasticizers in the manufacturing of flexible, plastic medical products. Patients can be subjected to high phthalate exposure through contact with plastic medical devices. We aimed to investigate the cardiac safety and biocompatibility of mono-2-ethylhexyl phthalate (MEHP), a phthalate with documented exposure in intensive care patients.
Methods
Optical mapping of transmembrane voltage and pacing studies were performed on isolated, Langendorff-perfused rat hearts to assess cardiac electrophysiology after MEHP exposure compared with controls. MEHP dose was chosen based on reported blood concentrations after an exchange transfusion procedure.
Results
Thirty-minute exposure to MEHP increased the atrioventricular node (147 versus 107 ms) and ventricular (117 versus 77.5 ms) effective refractory periods, compared with controls. Optical mapping revealed prolonged action potential duration at slower pacing cycle lengths, akin to reverse use dependence. The plateau phase of the action potential duration restitution curve steepened and became monophasic in MEHP-exposed hearts (0.18 versus 0.06 slope). Action potential duration lengthening occurred during late-phase repolarization resulting in triangulation (70.3 versus 56.6 ms). MEHP exposure also slowed epicardial conduction velocity (35 versus 60 cm/s), which may be partly explained by inhibition of Na1.5 (874 and 231 µmol/L half-maximal inhibitory concentration, fast and late sodium current).
Conclusions
This study highlights the impact of acute MEHP exposure, using a clinically relevant dose, on cardiac electrophysiology in the intact heart. Heightened clinical exposure to plasticized medical products may have cardiac safety implications-given that action potential triangulation and electrical restitution modifications are a risk factor for early after depolarizations and cardiac arrhythmias.



Circ Arrhythm Electrophysiol: 29 Jun 2019; 12:e007294
Jaimes R, McCullough D, Siegel B, Swift L, ... Tereshchenko LG, Posnack NG
Circ Arrhythm Electrophysiol: 29 Jun 2019; 12:e007294 | PMID: 31248280
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Abstract

Mexiletine Shortens the QT Interval in Patients With Potassium Channel-Mediated Type 2 Long QT Syndrome.

Bos JM, Crotti L, Rohatgi RK, Castelletti S, ... Schwartz PJ, Ackerman MJ
Background
Long QT syndrome is a potentially lethal yet highly treatable cardiac channelopathy. Although β-blocker therapy is standard for most patients, concomitant therapy with sodium channel blockers, like mexiletine, is often utilized for patients with sodium channel-mediated type 3 long QT syndrome (LQT3). The potential role of sodium channel blockers in patients with potassium channel-mediated long QT syndrome (ie, LQT1 and LQT2) has not been investigated in detail.
Methods
We performed a retrospective chart review on 12 patients (5 females; median age at diagnosis 14.1 years (interquartile range [IQR], 7.7-23; range, 0-59, median heart rate-corrected QT interval [QTc] at diagnosis 557 ms (IQR, 529-605) with genetically established LQT2 (10) or a combination of LQT1/LQT2 (1) or LQT2/LQT3 (1), who received mexiletine. Data were collected on symptomatic status, treatments, and breakthrough cardiac events after diagnosis and initiation of treatment. Additionally, 12-lead ECGs were collected at diagnosis, before initiation of mexiletine and following mexiletine to evaluate the drug\'s effect on QTc.
Results
Before diagnosis, 6 patients were symptomatic and, before initiation of mexiletine, 4 patients experienced ≥1 breakthrough cardiac event on β-blocker. Median age at first mexiletine dose was 24.3 years (IQR, 14-32.4). After mexiletine, the median QTc decreased by 65±45 ms from 547 ms (IQR, 488-558) premexiletine to 470 ms (IQR, 409-529) postmexiletine ( P=0.0005) for all patients. In 8 patients (67%), the QTc decreased by ≥ 40 ms with a mean decrease in QTc of 91 ms ( P < 0.008). For the 11 patients maintained on mexiletine therapy, there have been no breakthrough cardiac events during follow-up.
Conclusions
Although commonly prescribed in patients with LQT3, mexiletine also shortens the QTc significantly in two-thirds of a small subset of patients with potassium channel-mediated LQT2. In patients with LQT2, pharmacological targeting of the physiological late sodium current may provide added therapeutic efficacy to β-blocker therapy.



Circ Arrhythm Electrophysiol: 29 Apr 2019; 12:e007280
Bos JM, Crotti L, Rohatgi RK, Castelletti S, ... Schwartz PJ, Ackerman MJ
Circ Arrhythm Electrophysiol: 29 Apr 2019; 12:e007280 | PMID: 31006312
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Impact:
Abstract

Comparison Between Contact Force Monitoring and Unipolar Signal Modification as a Guide for Catheter Ablation of Atrial Fibrillation.

Ejima K, Kato K, Okada A, Wakisaka O, ... Shoda M, Hagiwara N
Background
Both contact force monitoring (CFM) and unipolar signal modification (USM) are guides for ablation, which improve the efficacy of pulmonary vein isolation of atrial fibrillation. We sought to compare the outcomes of atrial fibrillation ablation guided by CFM or USM.
Methods
A total of 136 patients with paroxysmal atrial fibrillation underwent a circumferential pulmonary vein isolation using CF sensing ablation catheters and were randomly assigned to undergo catheter ablation guided by either CFM (CFM-guided group: n=70) or USM (USM-guided group: n=66). In the USM-guided group, each radiofrequency application lasted until the development of completely positive unipolar electrograms. In the CFM-guided group, a CF of 20 g (range, 10-30 g) and minimum force-time integral of 400 g were the targets for each radiofrequency application. The primary end point was freedom from any atrial tachyarrhythmia recurrence without antiarrhythmic drugs at 12-months of follow-up.
Results
The cumulative freedom from recurrences at 12-months was 85% in the USM-guided group and 70% in the CFM-guided group (P=0.031). The incidence of time-dependent and ATP-provoked early electrical reconnections between the left atrium and PVs, procedural time, fluoroscopic time, and average force-time integral, did not significantly differ between the 2 groups. The radiofrequency time for the pulmonary vein isolation was shorter in the USM-guided group than CFM-guided group but was not statistically significant (P=0.077).
Conclusions
USM was superior to CFM as an end point for radiofrequency energy deliveries during the pulmonary vein isolation in patients with paroxysmal atrial fibrillation in terms of the 12-month recurrence-free rate.
Clinical trial registration
URL: https://www.umin.ac.jp/ctr/index.htm. Unique identifier: UMIN000021127.



Circ Arrhythm Electrophysiol: 30 Jul 2019; 12:e007311
Ejima K, Kato K, Okada A, Wakisaka O, ... Shoda M, Hagiwara N
Circ Arrhythm Electrophysiol: 30 Jul 2019; 12:e007311 | PMID: 31345092
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Impact:
Abstract

Impact of Leadless Pacemaker Therapy on Cardiac and Atrioventricular Valve Function Through 12 Months of Follow-Up.

Beurskens NEG, Tjong FVY, de Bruin-Bon RHA, Dasselaar KJ, ... Wilde AAM, Knops RE
Background
Endocardial pacemaker leads and right ventricular (RV) pacing are well-known causes of tricuspid valve, mitral valve, and cardiac dysfunction. Lead-related adverse consequences can potentially be mitigated by leadless pacemaker (LP) therapy by eliminating the presence of a transvalvular lead. This study assessed the impact of LP placement on cardiac and valvular structure and function.
Methods
Echocardiographic studies before and 12±1 months after LP implantation were performed between January 2013 and May 2018 at our center and compared with age- and sex-matched controls of dual-chamber transvenous pacemaker recipients.
Results
A total of 53 patients receiving an LP were included, of whom 28 were implanted with a Nanostim and 25 with a Micra LP device. Tricuspid valve regurgitation was graded as being more severe in 23 (43%) patients at 12±1 months compared with baseline ( P<0.001). Compared with an apical position, an RV septal position of the LP was associated with increased tricuspid valve incompetence (odds ratio, 5.20; P=0.03). An increase in mitral valve regurgitation was observed in 38% of patients ( P=0.006). LP implantation resulted in a reduction of RV function, according to a lower tricuspid annular plane systolic excursion ( P=0.003) and RV tricuspid lateral annular systolic velocity ( P=0.02), and a higher RV Tei index ( P=0.04). LP implantation was further associated with a reduction of left ventricular ejection fraction ( P=0.03) and elevated left ventricular Tei index ( P=0.003). The changes in tricuspid valve regurgitation in the LP group were similar to the changes in the dual-chamber transvenous pacemaker control group (43% versus 38%, respectively; P=0.39).
Conclusions
LP therapy is associated with an increase in tricuspid valve dysfunction through 12 months of follow-up; yet it was comparable to dual-chamber transvenous pacemaker systems. Furthermore, LP therapy seems to adversely impact mitral valve and biventricular function.



Circ Arrhythm Electrophysiol: 29 Apr 2019; 12:e007124
Beurskens NEG, Tjong FVY, de Bruin-Bon RHA, Dasselaar KJ, ... Wilde AAM, Knops RE
Circ Arrhythm Electrophysiol: 29 Apr 2019; 12:e007124 | PMID: 31060371
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Impact:
Abstract

Feasibility of An Entirely Extracardiac, Minimally Invasive,Temporary Pacing System.

Quast ABE, Beurskens NEG, Ebner A, Wasley R, ... Knops RE, Burke MC
Background
A completely extracardiac pacing system provides the potential for clinical advantages over existing device alternatives that require intravascular, endocardial, or epicardial contact. Preliminary studies evaluating the feasibility of cardiac pacing with a lead in the anterior mediastinum, outside the pericardium and circulatory system have been completed. These studies examined (1) the anatomic access route, (2) the usability of a delivery tool to facilitate lead placement, and (3) the pacing performance of the extracardiac lead.
Methods
Feasibility evaluations included (1) a retrospective computed tomography analysis to characterize anatomic variations related to lead access, (2) accessing the anterior mediastinum in cadavers and human subjects using a custom delivery tool, and (3) acute clinical pacing performance.
Results
Major findings: (1) A total of 166 (95%) out of 174 patients had a viable lead access path through the fourth, fifth, or sixth intercostal space. (2) Access to the targeted implant location using a delivery tool was successful in all 5 cadavers and 3 humans without use of fluoroscopy and with an average lead delivery time of 121±52 s. No damage to the lung, pericardium, heart, or internal thoracic vessels occurred. (3) Pacing performance was tested in 6 human subjects showing a threshold voltage of 4.7 V (2.7-6.7), threshold pulse width of 1.8 ms (1.0-2.5), and an impedance of 1205 Ω (894-1786). R-wave amplitudes measured 9.6 mV (5.6-12.0).
Conclusions
Results support the feasibility for this completely extracardiac pacing method in a heterogeneous patient population, using a minimally invasive, parasternal, delivery approach and with adequate sensing and thresholds suited for temporary pacing.



Circ Arrhythm Electrophysiol: 29 Jun 2019; 12:e007182
Quast ABE, Beurskens NEG, Ebner A, Wasley R, ... Knops RE, Burke MC
Circ Arrhythm Electrophysiol: 29 Jun 2019; 12:e007182 | PMID: 31266354
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Impact:
Abstract

Association of Left Atrial High-Resolution Late Gadolinium Enhancement on Cardiac Magnetic Resonance with Electrogram Abnormalities Beyond Voltage in Patients with Atrial Fibrillation.

Kuo L, Zado E, Frankel D, Santangeli P, ... Nazarian S, Desjardins B

- Conflicting data have been reported on the association of left atrial (LA) late gadolinium enhancement (LGE) with atrial voltage in patients with atrial fibrillation. The association of LGE with electrogram (EGM) fractionation and delay remains to be examined. We sought to examine the association between LA LGE on cardiac magnetic resonance (CMR) and EGM abnormalities in patients with atrial fibrillation (AF).- High-resolution LGE CMR was performed prior to EGM mapping and ablation in AF patients. CMR features were quantified using LA myocardial signal intensity z-score (SI-Z), a continuous normalized variable, as well as a dichotomous LGE variable based upon previously validated methodology. EGM mapping was performed pre-ablation during sinus rhythm or LA pacing, and EGM locations were co-registered with CMR images. Analyses were performed using multi-level patient-clustered mixed effects regression models.- In the 40 AF patients (age 63.2 ± 9.2 years, 1312.3 ± 767.3 EGM points per patient), lower bipolar voltage was associated with higher SI-Z in patients who had undergone previous ablation (coefficient=-0.049, p<0.001), but not in ablation-naïve patients (coefficient=-0.004, p=0.7). LA EGM activation delay was associated with SI-Z in patients with previous ablation (SI-Z: coefficient=0.004, p<0.001; LGE: coefficient=0.04, p<0.001) but not in ablation-naïve patients. In contrast, increased LA EGM fractionation was associated with SI-Z (coefficient=0.012, p=0.03) and LGE (coefficient=0.035, P<0.001) only in ablation-naïve patients.- The association of LA LGE with voltage is modified by ablation. Importantly, in ablation naïve patients, atrial LGE is associated with EGM fractionation even in the absence of voltage abnormalities.



Circ Arrhythm Electrophysiol: 14 Jan 2020; epub ahead of print
Kuo L, Zado E, Frankel D, Santangeli P, ... Nazarian S, Desjardins B
Circ Arrhythm Electrophysiol: 14 Jan 2020; epub ahead of print | PMID: 31940244
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Impact:
Abstract

Effect of Activation Wavefront on Electrogram Characteristics During Ventricular Tachycardia Ablation.

Martin CA, Martin R, Maury P, Meyer C, ... Jaïs P, Sacher F

Background Catheter ablation of ventricular tachycardia (VT) in structural heart disease is challenging because of noninducibility or hemodynamic compromise. Ablation often depends on elimination of local abnormal ventricular activities (LAVAs) but which may be hidden in far-field signal. We investigated whether altering activation wavefront affects activation timing and LAVA characterization and allows a better understanding of isthmus anatomy. Methods Patients with ischemic cardiomyopathy underwent mapping using the ultra-high density Rhythmia system (Boston Scientific). Maps were generated for all stable VTs and with pacing from the atrium, right ventricular apex, and an left ventricular branch of the coronary sinus. Results Fifty-six paced maps and 23 VT circuits were mapped in 22 patients. In 79% of activation maps, there was ≥1 line of block in the paced conduction wavefront, with 93% having fixed block and 32% showing functional partial block. Bipolar scar was larger with atrial than right ventricular (31.7±18.5 versus 27.6±16.3 cm, P=0.003) or left ventricular pacing (31.7±18.5 versus 27.0±19.2 cm, P=0.009); LAVA areas were smaller with atrial than right ventricular (12.3±10.5 versus 18.4±11.0 cm, P<0.001) or left ventricular pacing (12.3±10.5 versus 17.1±10.7 cm, P<0.001). LAVA areas were larger with wavefront propagation perpendicular versus parallel to the line of block along isthmus boundaries (19.3±7.1 versus 13.6±7.4 cm, P=0.01). All patients had successful VT isthmus ablation. In 11±8 months follow-up, 2 patients had a recurrence. Conclusions Wavefronts of conduction slowing/block may aid identification of critical isthmuses in unmappable VTs. Altering the activation wavefront leads to significant differences in conduction properties of myocardial tissue, along with scar and LAVA characterization. In patients where few LAVAs are identified during substrate mapping, using an alternate activation wavefront running perpendicular to the VT isthmus may increase sensitivity to detect arrhythmogenic substrate and critical sites for reentry.



Circ Arrhythm Electrophysiol: 30 May 2019; 12:e007293
Martin CA, Martin R, Maury P, Meyer C, ... Jaïs P, Sacher F
Circ Arrhythm Electrophysiol: 30 May 2019; 12:e007293 | PMID: 31122054
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Abstract

Protein Biomarkers and Risk of Atrial Fibrillation: The Framingham Heart Study.

Staerk L, Preis SR, Lin H, Lubitz SA, ... Benjamin EJ, Trinquart L

- Identification of protein biomarkers associated with incident atrial fibrillation (AF) may improve the understanding of the pathophysiology, risk prediction, and development of new therapeutics for AF. We examined the associations between 85 protein biomarkers and incident AF.- We included participants Ȧ5;50 years of age from the Framingham Heart Study Offspring and Third Generation cohorts, who had 85 fasting plasma proteins measured using Luminex xMAP platform. Hazard ratios (per 1 standard deviation increment of rank normalized biomarker [HR]) and 95% confidence intervals (CI) for incident AF were calculated using Cox regression models adjusted for age, sex, height, weight, current smoking, systolic blood pressure, diastolic blood pressure, hypertension treatment, diabetes, valvular heart disease, prevalent myocardial infarction, and prevalent heart failure. We used the False Discovery Rate to account for multiple testing.- The study sample comprised 3378 participants (54% women), with mean (SD) age of 61.5 (8.4) years. In total, 401 developed AF over a mean follow-up of 12.3±3.8 years. We observed lower hazard of incident AF associated with higher mean levels of insulin-like growth factor 1 (IGF1) (HR per 1 standard deviation increment in protein level = 0.84; 95% CI, 0.76-0.93), and higher hazard of incident AF associated with higher mean levels of both insulin-like growth factor-binding protein 1 (IGFBP1) (HR = 1.24; 95% CI, 1.1-1.39) and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) (HR = 1.73; 95% CI, 1.52-1.96).- Decreased levels of IGF1 and increased levels of IGFBP1 and NT-proBNP were associated with higher risk of incident AF.



Circ Arrhythm Electrophysiol: 14 Jan 2020; epub ahead of print
Staerk L, Preis SR, Lin H, Lubitz SA, ... Benjamin EJ, Trinquart L
Circ Arrhythm Electrophysiol: 14 Jan 2020; epub ahead of print | PMID: 31941368
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Abstract

Physiological Left Bundle Branch Pacing Validated by Ultra-high Density Ventricular Mapping in a Swine Model.

Qian Z, Hou X, Wang Y, Jiang H, ... Wang B, Zou J

Left bundle branch (LBB) pacing was first reported by Huang et al in 2017 and following studies demonstrated that LBB pacing could provide favorable left ventricular (LV) electrical and mechanical synchrony. However, the mechanism of LV activation during LBB pacing is not fully understood. This study aimed to elucidate the detailed LV endocardial activation during LBB pacing in a swine model using an ultra-high density electroanatomic mapping system.



Circ Arrhythm Electrophysiol: 13 Jan 2020; epub ahead of print
Qian Z, Hou X, Wang Y, Jiang H, ... Wang B, Zou J
Circ Arrhythm Electrophysiol: 13 Jan 2020; epub ahead of print | PMID: 31935122
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Abstract

Atrial Fibrillation Catheter Ablation Improves 1-Year Follow-Up Cognitive Function, Especially in Patients With Impaired Cognitive Function.

Jin MN, Kim TH, Kang KW, Yu HT, ... Kim E, Pak HN
Background
Although atrial fibrillation (AF) has a risk of cognitive dysfunction, it is not clear whether AF catheter ablation improves or worsens cognitive function. This prospective case-control study sought to assess the 1-year serial changes in the cognitive function with or without AF catheter ablation.
Methods
We evaluated the Montreal Cognitive Assessment score in 308 patients (71.4% male, 60.6±9.1 years of age, 34.1% persistent AF) who underwent AF ablation (ablation group) and 50 AF patients on medical therapy who met the same indication for AF ablation (control group), at baseline and 3 and 12 months after enrollment. Cognitive impairment was defined as a published cutoff score of <23 points. To exclude any learning effects, we used the practice-adjusted reliable change index for assessing the cognitive changes.
Results
Preablation cognitive impairment was detected in 18.5% (57/308). The Montreal Cognitive Assessment score significantly improved 1 year after radiofrequency catheter ablation in both overall ablation group (24.9±2.9-26.4±2.5; P<0.001) and the propensity-matched ablation group (25.4±2.4-26.5±2.3; P<0.001), but not in the control group (25.4±2.5-24.8±2.5; P=0.012). Preablation cognitive impairment (odds ratio, 13.70; 95% CI, 4.83-38.87; P<0.001) was independently associated with an improvement in the 1-year post-ablation cognitive function. In the reliable change index analyses, 94.7% of propensity-matched ablation group showed an improved/stable cognitive function at the 1-year follow-up.
Conclusions
Catheter ablation of AF, at least, does not deteriorate the cognitive function, but rather improves the performance on 1-year follow-up neurocognitive tests, especially in patients with a preablation cognitive impairment.



Circ Arrhythm Electrophysiol: 29 Jun 2019; 12:e007197
Jin MN, Kim TH, Kang KW, Yu HT, ... Kim E, Pak HN
Circ Arrhythm Electrophysiol: 29 Jun 2019; 12:e007197 | PMID: 31442075
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Abstract

Differences by Race/Ethnicity in the Prevalence of Clinically-detected and Monitor-detected Atrial Fibrillation: The Multi-Ethnic Study of Atherosclerosis.

Heckbert SR, Austin TR, Jensen PN, Chen LY, ... Kronmal RA, Psaty BM

- African Americans are consistently found to have a lower prevalence of clinically-detected atrial fibrillation (AF) than whites, despite a higher prevalence of major AF risk factors and higher risk of ischemic stroke. Long-term ambulatory electrocardiographic (ECG) monitors provide the opportunity for unbiased AF detection. We determined differences by race/ethnicity in the prevalence of clinically-detected AF and in the proportion with monitor-detected AF.- We conducted a cross-sectional analysis in the Multi-Ethnic Study of Atherosclerosis (MESA), a community-based cohort study that enrolled 6814 Americans free of clinically-recognized cardiovascular disease in 2000-2002. At the 2016-2018 examination, 1556 individuals participated in an ancillary study involving ambulatory ECG monitoring and had follow-up for clinically-detected AF since cohort entry.- Among 1556 participants, 41% were white, 25% African American, 21% Hispanic, and 14% Chinese; 51% were women; and the mean age was 74 years. The prevalence of clinically-detected AF after 14.4 years\' follow-up was 11.3% in whites, 6.6% in African Americans, 7.8% in Hispanics, and 9.9% in Chinese, and was significantly lower in African Americans than in whites, in both unadjusted and risk factor-adjusted analyses (adjusted rate difference, -6.6%, 95% CI -10.1, -3.1%, P < 0.001). By contrast, in the same individuals, the proportion with monitor-detected AF using a 14-day ambulatory ECG monitor was similar in the four race/ethnic groups: 7.1%, 6.4%, 6.9%, and 5.2%, respectively (compared with whites, all P > 0.5).- The prevalence of clinically-detected AF was substantially lower in African American than in white participants, without or with adjustment for AF risk factors. However, unbiased AF detection by ambulatory monitoring in the same individuals revealed little difference in the proportion with AF by race/ethnicity. These findings provide support for the hypothesis of differential detection by race/ethnicity in the clinical recognition of AF, which may have important implications for stroke prevention.



Circ Arrhythm Electrophysiol: 13 Jan 2020; epub ahead of print
Heckbert SR, Austin TR, Jensen PN, Chen LY, ... Kronmal RA, Psaty BM
Circ Arrhythm Electrophysiol: 13 Jan 2020; epub ahead of print | PMID: 31934795
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Abstract

Evaluation of ECG Imaging to Map Haemodynamically Stable and Unstable Ventricular Arrhythmias.

Graham AJ, Orini M, Zacur E, Dhillon G, ... Schilling RJ, Lambiase PD

- ECG Imaging (ECGI) has been used to guide treatment of ventricular ectopy and arrhythmias. However, the accuracy of ECGI in localizing the origin of arrhythmias during catheter ablation of ventricular tachycardia (VT) in structurally abnormal hearts remains to be fully validated.- During catheter ablation of VT, simultaneous mapping was performed using electro-anatomical mapping (EAM) (CARTO, Biosense-Webster) and ECGI (CardioInsight™, Medtronic) in 18 patients. Sites of entrainment, pace-mapping and termination during ablation were used to define the VT site of origin (SoO). Distance between SoO and the site of earliest activation on ECGI were measured using co-registered geometries from both systems. The accuracy of ECGI vs a 12-lead surface ECG algorithm was compared.- A total of 29 VTs were available for comparison. Distance between SoO and sites of earliest activation in ECGI was 22.6, 13.9-36.2 mm (median, first-third quartile). ECGI mapped VT sites of origin onto the correct AHA segment with higher accuracy than a validated 12-lead ECG algorithm (83.3% vs 38.9%, P=0.015).- This simultaneous assessment demonstrates that CardioInsight™ localizes VT circuits with sufficient accuracy to provide a region of interest for targeting mapping for ablation. Resolution is not sufficient to guide discrete radiofrequency lesion delivery via catheter ablation without concomitant use of an electro-anatomical mapping system, but may be sufficient for segmental ablation with radiotherapy.



Circ Arrhythm Electrophysiol: 13 Jan 2020; epub ahead of print
Graham AJ, Orini M, Zacur E, Dhillon G, ... Schilling RJ, Lambiase PD
Circ Arrhythm Electrophysiol: 13 Jan 2020; epub ahead of print | PMID: 31934784
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Abstract

Mechanism of Recurrence of AT: Comparison between First Vs. Redo Procedures in a High-resolution Mapping System.

Takigawa M, Derval N, Martin CA, Vlachos K, ... Haïssaguerre M, Jaïs P

- Atrial fibrillation (AF) ablation related atrial tachycardia (AFA-rAT) is complex, and may demonstrate several forms: anatomical macroreenrant AT (AMAT), Non-AMAT, and focal AT. We aimed to elucidate the recurrence rate and mechanisms of AFA-rAT recurrence.- Among 147 patients with ATs treated with the Rhythmia™-system, 68 (46.3%) had recurrence at mean 4.2[2.9-11.6] months and 44 patients received a redo procedure. AT circuits in the first procedure were compared to those in the redo procedure.- Although mappable ATs were not observed in 7 patients, 68 ATs were observed in 37 patients during the first procedure: peri-mitral flutter (PMF) in 26 patients, roof-dependent macroreentrant-AT (RMAT) in 18, peri-tricuspid flutter (PTF) in 10, Non-AMAT in 14, and focal AT in 3. During the redo AT ablation procedure, 54 ATs were observed in 41 patients: PMF in 24, RMAT in 14, PTF in 1, Non-AMAT in 14, and focal AT in 1. Recurrence of PMF and RMAT was observed in 15/26 (57.7%) and 8/18 (44.4%) respectively, while PTF did not recur. Neither the same focal AT nor the same Non-AMAT were observed except in one case with septal scar related biatrial-AT. Epicardial structure-related ATs were involved in 18/24 (75.0%) in PMF, 4/14 (28.6%) in RMAT, and 4/14 (28.6%) in Non-AMAT. Out of 21 patients with a circuit including epicardial structures, 6 patients treated with ethanol-infusion in the vein of Marshall (VOM) did not show any AT-recurrence, though 8/15 (53.3%) treated with RF showed AT-recurrence (P=0.04).- Although high-resolution mapping may lead to correct diagnosis and appropriate ablation in the first procedure, the recurrence rate is still high. The main mechanism of AFA-rAT is the recurrence of PMF and RMAT, or Non-AMAT different from the first procedure. Epicardial structures (e.g. coronary sinus/VOM system) are often involved, and ethanol-infusion in the VOM may be an additional treatment.



Circ Arrhythm Electrophysiol: 13 Jan 2020; epub ahead of print
Takigawa M, Derval N, Martin CA, Vlachos K, ... Haïssaguerre M, Jaïs P
Circ Arrhythm Electrophysiol: 13 Jan 2020; epub ahead of print | PMID: 31937120
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Abstract

Efficacy of Pharmacologic and Cardiac Implantable Electronic Device Therapies in Patients With Heart Failure and Reduced Ejection Fraction.

Tseng AS, Kunze KL, Lee JZ, Amin M, ... Gersh BJ, Mulpuru SK

Background The treatment of heart failure with reduced ejection fraction has been the subject of numerous randomized controlled trials involving medications and cardiac implantable electronic device therapies. As newer effective pharmacological therapies suggest significant reductions in all-cause mortality, the role of additional device therapy in heart failure with reduced ejection fraction deserves further scrutiny. Methods A systematic review and network meta-analysis on the effect of medication and device therapies in heart failure with reduced ejection fraction on all-cause mortality was performed. Randomized controlled trials published between January 1980 and July 2017 were identified using Medline, EMBASE, and Cochrane Controlled Register of Trials databases. Pcnetmeta package in R was used to calculate treatment arm-based estimated rates, rate ratios, and probability ranks with 95% credible intervals. Results Combination therapy of ACE (angiotensin-converting enzyme) inhibitors or ARBs (angiotensin receptor blockers) with β-blockers (BBs) alone or in addition to implantable cardiac defibrillators or cardiac resynchronization therapy with defibrillators demonstrated a significant reduction of all-cause mortality when compared with placebo. By probability rank, implantable cardiac defibrillator+ACE inhibitor or ARB+BB+mineralocorticoid receptor antagonist, implantable cardiac defibrillator+ACE inhibitor or ARB+BB, and angiotensin receptor-neprilysin inhibitor+BB+mineralocorticoid receptor antagonist combination therapies have the highest probability of being ranked the best treatment. There was no significant difference in the rate of mortality when comparing angiotensin receptor-neprilysin inhibitor+BB+mineralocorticoid receptor antagonist to implantable cardiac defibrillator+optimal pharmacological combination therapy. Conclusions BB and renin-angiotensin system blockers alone or in combination with defibrillator device therapy have robust evidence for a reduction in mortality compared with placebo. The comparative efficacy of pharmacological therapy with angiotensin receptor-neprilysin inhibitors and device therapy deserves further investigation.



Circ Arrhythm Electrophysiol: 30 May 2019; 12:e006951
Tseng AS, Kunze KL, Lee JZ, Amin M, ... Gersh BJ, Mulpuru SK
Circ Arrhythm Electrophysiol: 30 May 2019; 12:e006951 | PMID: 31159582
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Abstract

Epicardial Connections Involving Pulmonary Veins: The Prevalence, Predic-tors and Implications for Ablation Outcome.

Barrio-López MT, Sanchez-Quintana D, Garcia Martinez J, Betancur A, ... Garcia F, Almendral J

- The presence of epicardial connections (ECs) between pulmonary veins (PVs) and other anatomical structures may hinder PV isolation. In this study we analyzed their prevalence, location, associated factors and clinical implications.- Five hundred and thirty-four consecutive patients with atrial fibrillation (AF) undergoing radiofrequency ablation were included. We considered that an EC was present if: 1) the first pass around the PV antrum did not produce PV isolation and 2) subsequent atrial activation during PV pacing showed that the earliest site was located away from the ablation line and later activation sites were observed near the ablation line. Clinical, and electrophysological variables were collected from all patients. Patients were followed during 12.9±9.4 months and any documented atrial tachyarrhythmia after the 3-month blanking period was classified as a recurrence.- Out of the 534 patients included, 72 (13.5%) were found to have 81 ECs. There was a significant association between the presence ECs and structural heart disease (SHD) (15.3% in patients without ECs vs. 36.5% in patient with ECs; p<0.001) and patent foramen ovale (PFO) (4.6% vs. 13.5%; p=0.002). The presence of a left common trunk was significantly associated with the absence of ECs (29.6% in patients without ECs vs 16.2% in patients with ECs; p=0.014). Patients with ECs had lower acute success in PV isolation compared with patients without ECs (99.1% vs. 86.1%; p<0.001). After adjusting for age, sex, type of AF, LA area, hypertension, SHD, presence of left common trunk, patent foramen ovale and time for AF diagnosis to the ablation we found a significantly higher risk of atrial tachyarrhythmia recurrences in patients with ECs compared with patients without ECs (hazard ratio: 1.7; 95% confidence inter-val: 1.1-2.9; p=0.04).- ECs between PVs and other adjacent structures are frequent in patient with AF (prevalence: 13.5%). SHD and a PFO are strongly associated with the presence of ECs. ECs reduce the acute and chronic success of PV isolation.



Circ Arrhythm Electrophysiol: 14 Jan 2020; epub ahead of print
Barrio-López MT, Sanchez-Quintana D, Garcia Martinez J, Betancur A, ... Garcia F, Almendral J
Circ Arrhythm Electrophysiol: 14 Jan 2020; epub ahead of print | PMID: 31940223
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Abstract

Differentiating Atrioventricular Reentry Tachycardia and AV Node Reentry Tachycardia Using Premature His Bundle Complexes.

Padanilam BJ, Ahmed AS, Clark BA, Gilge JL, ... Prystowsky EN, Steinberg LA

- Current maneuvers for differentiation of AV node reentry tachycardia (AVNRT) and atrioventricular reentry tachycardia (AVRT) lack sensitivity and specificity for AVRT circuits located away from the site of pacing. We hypothesized that a premature His complex (PHC) will always perturb AVRT because the His bundle is obligatory to the circuit. Further, AVNRT could not be perturbed by a late PHC (Ȧ4; 20 ms ahead of the His) due to the retrograde His conduction time. Earlier PHCs can advance the AVNRT circuit but only by a quantity less than the prematurity of the PHC.- High output pacing at the distal His location delivered PHCs. AVRT was predicted when late PHCs perturbed tachycardia or when earlier PHCs led to atrial advancement by an amount equal or greater than the degree of PHC prematurity.- Among the 73 SVTs, the test accurately predicted AVRT (n=29) and AVNRT (n=44) in all cases. Late PHC advanced the circuit in all 29 AVRTs and none of the AVNRTs (sensitivity and specificity 100%). With earlier PHCs, the degree of atrial advancement was equal or greater than the PHC prematurity in 26/29 AVRTs and none of the AVNRTs (90% sensitivity and 100% specificity). The mean prematurity of the PHC required to perturb AVNRT was 48 ms (range 28-70 ms) and the advancement less than the prematurity of the PHC (mean 32 ms; range 18-54 ms).- The responses to PHCs distinguished AVRT and AVNRT with 100% specificity and sensitivity.



Circ Arrhythm Electrophysiol: 13 Jan 2020; epub ahead of print
Padanilam BJ, Ahmed AS, Clark BA, Gilge JL, ... Prystowsky EN, Steinberg LA
Circ Arrhythm Electrophysiol: 13 Jan 2020; epub ahead of print | PMID: 31934781
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Abstract

Higher Incidence of Asymptomatic Cerebral Emboli after Atrial Fibrillation Ablation Found with High-resolution Diffusion-weighted MRI.

Yu Y, Wang X, Li X, Zhou X, ... Yang B, Chen M

- Asymptomatic cerebral emboli (ACE) are commonly seen on cerebral MRI after atrial fibrillation (AF) ablation, but the incidence in previous studies varies widely. No data exists to compare the effects of different diffusion-weighted imaging (DWI) settings on detecting ablation-related ACE. This self-control study sought to compare the incidence and characteristics of ablation-related ACE between high-resolution DWI (hDWI) and conventional DWI (cDWI).- A total of 55 consecutive patients referred for AF ablation between December 2017 and September 2018 were enrolled. Patients underwent hDWI one day prior to ablation and repeated hDWI and cDWI within 48 hours post-ablation. The incidence, number, size, and location of ACE were compared between two DWI settings in the same patients.The hDWI revealed a higher incidence of acute ACE compared to cDWI (67.3% vs. 41.8% of patients, P <0.001) and significantly more ACE (106 vs. 45 lesions, P = 0.001). For ACE seen on both scans, the size measured by hDWI was larger (5.42 vs. 4.21 mm, P <0.001). No patients had any impaired neurocognitive performance during follow-up. Impaired left ventricular ejection fraction (LVEF) (P = 0.012) and low intraoperative activated clotting time (ACT) (P = 0.009) level were associated with the occurrence of ACE in a multivariate analysis.- High-resolution DWI revealed a higher incidence and greater details of post-ablation ACE in AF patients. MRI settings significantly impact the detection of ACE and should be considered when comparing incidence rates of ACE amongst different studies.- ClinicalTrials.gov; Unique Identifier: NCT01761188.



Circ Arrhythm Electrophysiol: 13 Jan 2020; epub ahead of print
Yu Y, Wang X, Li X, Zhou X, ... Yang B, Chen M
Circ Arrhythm Electrophysiol: 13 Jan 2020; epub ahead of print | PMID: 31937118
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Abstract

Arrhythmia Mechanisms and Outcomes of Ablation in Pediatric Patients With Congenital Heart Disease.

Houck CA, Chandler SF, Bogers AJJC, Triedman JK, ... de Groot NMS, Abrams DJ
Background
In contrast to the adult population with congenital heart disease (CHD), arrhythmia mechanisms and outcomes of ablation in pediatric patients with CHD in recent era have not been studied in detail. Aims of this study were to determine arrhythmia mechanisms and to evaluate procedural and long-term outcomes in pediatric patients with CHD undergoing catheter ablation.
Methods
Consecutive patients <18 years of age with CHD undergoing catheter ablation over an 11-year period (2007-2018) were included. Procedural outcome included complete or partial success, failure or empirical ablation. Long-term outcome included arrhythmia recurrence and burden according to a 12-point clinical arrhythmia severity score.
Results
The study population consisted of 232 patients (11.7 years [0.01-17.8], 33.5 kg [2.2-130.1]). The most common diagnoses were Ebstein\'s anomaly (n=44), septal defects (n=39), and single ventricle (n=36). Arrhythmia mechanisms included atrioventricular reentry tachycardia (n=104, 90 patients), atrioventricular nodal reentry tachycardia (n=33, 29 patients), twin atrioventricular nodal tachycardia (n=3, 2 patients), macroreentrant atrial tachycardia (n=59, 56 patients), focal atrial tachycardia (n=33, 25 patients), ventricular ectopy (n=10, 8 patients), and ventricular tachycardia (n=15, 13 patients). Fifty-six arrhythmias (39 patients) were undefined. Outcomes included complete success (n=189, 81%), partial success (n=7, 3%), failure (n=16, 7%), or empirical ablation (n=20, 9%). Over 3.6 years (0.3-10.7) arrhythmia recurred in 49%. Independent of arrhythmia recurrence, arrhythmia scores decreased from 4 (0-10) at baseline to 0.5 (0-8) at 4 years follow-up (<0.001). In 23/51 repeat procedures (45%), a different arrhythmia substrate was found. Overall adverse event rate was 9.4%, although only 1.6% (n=4) were of major severity and 0.8% (n=2) of moderate severity.
Conclusions
Pediatric patients with CHD demonstrate a broad spectrum of arrhythmia mechanisms. Despite recurrence and emergence of novel mechanisms after a successful procedure, ablation can be performed safely and successfully resulting in decreased arrhythmia burden.



Circ Arrhythm Electrophysiol: 30 Oct 2019; 12:e007663
Houck CA, Chandler SF, Bogers AJJC, Triedman JK, ... de Groot NMS, Abrams DJ
Circ Arrhythm Electrophysiol: 30 Oct 2019; 12:e007663 | PMID: 31722541
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Abstract

Can the Durability of Pulmonary Vein Isolation be Predicted by the Time-to-Isolation in Second-generation Cryoballoon Ablation? Insight from the Results of Repeat Procedures.

Miyazaki S, Kajiyama T, Watanabe T, Nakamura H, ... Tada H, Iesaka Y

Second-generation cryoballoons (2-CBs) are widely used in atrial fibrillation (AF) ablation, however, the optimal freeze dose is still under debate. Recently, the time-to-isolation (TTI), which is the time until an acute pulmonary vein isolation (PVI), is noted based on clinical and experimental studies, and a TTI-guided strategy has been proposed. However, in real-world human CB procedures, the direct association between the TTI and PVI durability has not been well examined. We sought to investigate whether the TTI plus >120 second freezes, when the TTI is <60 seconds, accurately predicts a durable 2-CB ablation PVI.



Circ Arrhythm Electrophysiol: 13 Jan 2020; epub ahead of print
Miyazaki S, Kajiyama T, Watanabe T, Nakamura H, ... Tada H, Iesaka Y
Circ Arrhythm Electrophysiol: 13 Jan 2020; epub ahead of print | PMID: 31935121
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Abstract

High-Power (40-50 W) Radiofrequency Ablation Guided by Unipolar Signal Modification for Pulmonary Vein Isolation.

Pambrun T, Durand C, Constantin M, Masse A, ... Jaïs P, Bortone A

Background Although proposed to facilitate pulmonary vein isolation (PVI), high-power ablation may favor extracardiac damage. Negative component abolition of the unipolar signal reflects lesion transmurality. The present study sought to evaluate the safety and efficacy of high-power ablation using unipolar signal modification as a local end point. Methods High power and standard power were compared in 4 swine and 100 consecutive patients referred for PVI. The first 50 patients were included in the control group (25-30 W) and the last 50 patients in the study group (40-50 W). Atrial radiofrequency applications were stopped 2 s (study group and swine) or 5 s (control group) after unipolar signal modification. Ventricular radiofrequency applications of 500 J (25 W·20 s versus 50 W·10 s) were performed at the swine epicardium. Results Swine gross necropsy did not show any extracardiac damage related to atrial lesions. At equal energy of 500 J, 50 W lesions were deeper (3±0.9 versus 2.6±1.1 mm; P=0.03) and wider (6.2±2 versus 5±2.3 mm; P=0.006) than 25 W lesions. No complications occurred during the clinical study, whatever the power output used for PVI. For a similar sinus rhythm maintenance at 12 months (90% versus 88%; P=0.75), the study group displayed higher first-pass PVI (92% versus 73%; P<0.001), lower acute pulmonary vein reconnection (2% versus 17%; P<0.001), reduced procedure time (73.1±18.2 versus 107.4±21.2 min; P<0.001), and ablation time (13±2.9 versus 30.3±8.8 min; P<0.001). Conclusions High-power PVI guided by unipolar signal modification safely decreases procedural burden while ensuring robust 12-month outcomes.



Circ Arrhythm Electrophysiol: 30 May 2019; 12:e007304
Pambrun T, Durand C, Constantin M, Masse A, ... Jaïs P, Bortone A
Circ Arrhythm Electrophysiol: 30 May 2019; 12:e007304 | PMID: 31164003
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Abstract

Myocarditis Causing Premature Ventricular Contractions: Insights From the MAVERIC Registry.

Lakkireddy D, Turagam MK, Yarlagadda B, Dar T, ... Gopinathannair R, Natale A
Background
Premature ventricular contractions are a common clinical presentation that drives further diagnostic workup. We hypothesize the presence of underlying inflammation is often unrecognized in these patients with a potential for continued disease progression if not diagnosed and treated early in the disease course.
Methods
This is a single-center, prospective study including 107 patients with frequent symptomatic premature ventricular contractions (>5000/24 h) and no known ischemic heart disease. Patients underwent a combination of laboratory testing, 18F-fluorodeoxyglucose positron emission tomography scan, cardiac magnetic resonance imaging, and biopsy. Patients were diagnosed with myocarditis based on a multidisciplinary approach and treated with immunosuppressive therapy.
Results
The mean age of the cohort was 57±15 years, 41% were males, and left ventricular ejection fraction was 47±11.8%. Positive positron emission tomography scan was seen in 51% (55/107), of which 51% (28/55) had preserved left ventricle function. Based on clinical profile, 18F-fluorodeoxyglucose-positron emission tomography imaging, cardiac magnetic resonance, and histological data 58% patients (32/55) received immunosuppressive therapy alone and 25.4% (14/55) received immunosuppressive therapy and catheter ablation. Optimal response was seen in 67% (31/46) over a mean follow-up of 6±3 months. In patients with left ventricle systolic dysfunction, 37% (10/27) showed an improvement in mean left ventricular ejection fraction of 13±6%.
Conclusions
Approximately 51% of patients presenting with frequent premature ventricular contractions have underlying myocardial inflammation in this cohort. 18F-fluorodeoxyglucose-positron emission tomography scan can be a useful modality for early diagnosis and treatment with immunosuppressive therapy in selected patients can improve clinical outcomes.



Circ Arrhythm Electrophysiol: 29 Nov 2019; 12:e007520
Lakkireddy D, Turagam MK, Yarlagadda B, Dar T, ... Gopinathannair R, Natale A
Circ Arrhythm Electrophysiol: 29 Nov 2019; 12:e007520 | PMID: 31838913
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Abstract

Insight Into the Mechanism of Macroreentrant Atrial Tachycardia With Cycle Length Alternans Using Ultrahigh Density Mapping System.

Zhang J, Zheng L, Zhou D, Zhao A, ... Zhang Y, Su X
Background
Atrial tachycardia (AT) with cycle length (CL) alternans is a rare phenomenon. We aimed to identify the characteristics and precise mechanism of this special category of ATs by using an ultrahigh density mapping system.
Methods
We identified 7 ATs with alternating CL in a total of 478 ATs from 2 institutions mapped with an ultrahigh density mapping system. Activation maps were performed for long CL (289±35 ms; mapping points, 21 520±11 103) and short CL (251±18 ms; mapping points,17 594±8059) separately.
Results
We classified ATs with CL alternans into 2 types. Type 1: There existed 2 potential loops with different routes. CL alternans resulted from an intermittently 2:1 conducting block within the channel of the smaller loop. Type 2: CL alternans resulted from different conduction velocity through 2 closely spaced gaps within preexisting linear lesions. Catheter ablation successfully terminated all the 7 ATs.
Conclusions
Ultrahigh density mapping provides an opportunity to delineate the precise mechanism of AT with CL alternans. Intermittent conduction block or slowing of a channel was essential for the maintenance of AT.



Circ Arrhythm Electrophysiol: 30 Oct 2019; 12:e007634
Zhang J, Zheng L, Zhou D, Zhao A, ... Zhang Y, Su X
Circ Arrhythm Electrophysiol: 30 Oct 2019; 12:e007634 | PMID: 31698935
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Abstract

Machine Learning Prediction of Response to Cardiac Resynchronization Therapy.

Feeny AK, Rickard J, Patel D, Toro S, ... Spragg DD, Chung MK
Background
Cardiac resynchronization therapy (CRT) has significant nonresponse rates. We assessed whether machine learning (ML) could predict CRT response beyond current guidelines.
Methods
We analyzed CRT patients from Cleveland Clinic and Johns Hopkins. A training cohort was created from all Johns Hopkins patients and an equal number of randomly sampled Cleveland Clinic patients. All remaining patients comprised the testing cohort. Response was defined as ≥10% increase in left ventricular ejection fraction. ML models were developed to predict CRT response using different combinations of classification algorithms and clinical variable sets on the training cohort. The model with the highest area under the curve was evaluated on the testing cohort. Probability of response was used to predict survival free from a composite end point of death, heart transplant, or placement of left ventricular assist device. Predictions were compared with current guidelines.
Results
Nine hundred twenty-five patients were included. On the training cohort (n=470: 235, Johns Hopkins; 235, Cleveland Clinic), the best ML model was a naive Bayes classifier including 9 variables (QRS morphology, QRS duration, New York Heart Association classification, left ventricular ejection fraction and end-diastolic diameter, sex, ischemic cardiomyopathy, atrial fibrillation, and epicardial left ventricular lead). On the testing cohort (n=455, Cleveland Clinic), ML demonstrated better response prediction than guidelines (area under the curve, 0.70 versus 0.65; P=0.012) and greater discrimination of event-free survival (concordance index, 0.61 versus 0.56; P<0.001). The fourth quartile of the ML model had the greatest risk of reaching the composite end point, whereas the first quartile had the least (hazard ratio, 0.34; P<0.001).
Conclusions
ML with 9 variables incrementally improved prediction of echocardiographic CRT response and survival beyond guidelines. Performance was not improved by incorporating more variables. The model offers potential for improved shared decision-making in CRT (online calculator: http://riskcalc.org:3838/CRTResponseScore ). Significant remaining limitations confirm the need to identify better variables to predict CRT response.



Circ Arrhythm Electrophysiol: 29 Jun 2019; 12:e007316
Feeny AK, Rickard J, Patel D, Toro S, ... Spragg DD, Chung MK
Circ Arrhythm Electrophysiol: 29 Jun 2019; 12:e007316 | PMID: 31216884
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Abstract

Deep Negative Deflection in Unipolar His-Bundle Electrogram as a Predictor of Excellent His-Bundle Pacing Threshold Postimplant.

Sato T, Soejima K, Maeda A, Mohri T, ... Ueda A, Togashi I

Background His-bundle pacing (HBP) is a physiological form of pacing. Although high capture thresholds are common, few predictors of low HBP threshold have been determined. We aimed to identify electrophysiological predictors. Methods Fifty-one patients (53% with atrioventricular block) underwent HBP for bradycardia with an intrinsic QRS duration of <120 ms. Attempts to anchor the HBP lead were guided by unipolar His-bundle electrograms (HB EGMs) recorded with an electrophysiology recording system. Patients were followed-up for >6 months. Results In total, 153 attempts at anchoring the HBP lead were made, of which, 45 achieved acceptable HBP thresholds (≤2.5 V at 1 ms). The amplitude of negative deflection in HB EGM and the selective HBP form at fixation were independently associated with achieving an acceptable threshold. A negative amplitude of ≥0.060 mV in HB EGM was determined as the optimal value for identifying the acceptable threshold. This deep negative HB EGM was recorded with an HBP threshold of 1.4±1.3 V (in 34 attempts), significantly lower than that of positive HB EGM without deep negative deflection (2.8±1.3 V, in 31 trials; or >5 V, in 38 trials). The permanent HBP lead remained with deep negative (≥0.060 mV) or positive HB EGMs in 28 and 14 patients, respectively, and with positive or negative HB injury current in 19 and 23 patients, respectively. During follow-up, increased HBP threshold of >1 V was significantly more prevalent in the positive HB EGM group. The HBP thresholds of deep negative HB EGM and HB injury current, but not of the selective HBP group, were significantly lower than the other subgroups during follow-up. Conclusions Deep negative HB EGM at fixation was associated with an excellent short-term HBP threshold, similar to HB injury current. Analysis of unipolar HB EGM postfixation may enable prediction of permanent HBP threshold.



Circ Arrhythm Electrophysiol: 30 May 2019; 12:e007415
Sato T, Soejima K, Maeda A, Mohri T, ... Ueda A, Togashi I
Circ Arrhythm Electrophysiol: 30 May 2019; 12:e007415 | PMID: 31113233
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Abstract

Genetic Discovery of ATP-Sensitive K Channels in Cardiovascular Diseases.

Huang Y, Hu D, Huang C, Nichols CG

The ATP-sensitive K (K) channels are hetero-octameric protein complexes comprising 4 pore-forming (Kir6.x) subunits and 4 regulatory sulfonylurea receptor (SURx) subunits. They are prominent in myocytes, pancreatic β cells, and neurons and link cellular metabolism with membrane excitability. Using genetically modified animals and genomic analysis in patients, recent studies have implicated certain ATP-sensitive K channel subtypes in physiological and pathological processes in a variety of cardiovascular diseases. In this review, we focus on the causal relationship between ATP-sensitive K channel activity and pathophysiology in the cardiovascular system, particularly from the perspective of genetic changes in human and animal models.



Circ Arrhythm Electrophysiol: 29 Apr 2019; 12:e007322
Huang Y, Hu D, Huang C, Nichols CG
Circ Arrhythm Electrophysiol: 29 Apr 2019; 12:e007322 | PMID: 31030551
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Abstract

Refining the World Health Organization Definition.

Tseng ZH, Salazar JW, Olgin JE, Ursell PC, ... Moffatt E, Vittinghoff E
Background
Conventional definitions of sudden cardiac death (SCD) presume cardiac cause. We studied the World Health Organization-defined SCDs autopsied in the POST SCD study (Postmortem Systematic Investigation of SCD) to determine whether premortem characteristics could identify autopsy-defined sudden arrhythmic death (SAD) among presumed SCDs.
Methods
Between January 2, 2011, and January 4, 2016, we prospectively identified all 615 World Health Organization-defined SCDs (144 witnessed) 18 to 90 years in San Francisco County for medical record review and autopsy via medical examiner surveillance. Autopsy-defined SADs had no extracardiac or acute heart failure cause of death. We used 2 nested sets of premortem predictors-an emergency medical system set and a comprehensive set adding medical record data-to develop Least Absolute Selection and Shrinkage Operator models of SAD among witnessed and unwitnessed cohorts.
Results
Of 615 presumed SCDs, 348 (57%) were autopsy-defined SAD. For witnessed cases, the emergency medical system model (area under the receiver operator curve 0.75 [0.67-0.82]) included presenting rhythm of ventricular tachycardia/fibrillation and pulseless electrical activity, while the comprehensive (area under the receiver operator curve 0.78 [0.70-0.84]) added depression. If only ventricular tachycardia/fibrillation witnessed cases (n=48) were classified as SAD, sensitivity was 0.46 (0.36-0.57), and specificity was 0.90 (0.79-0.97). For unwitnessed cases, the emergency medical system model (area under the receiver operator curve 0.68 [0.64-0.73]) included black race, male sex, age, and time since last seen normal, while the comprehensive (area under the receiver operator curve 0.75 [0.71-0.79]) added use of β-blockers, antidepressants, QT-prolonging drugs, opiates, illicit drugs, and dyslipidemia. If only unwitnessed cases <1 hour (n=59) were classified as SAD, sensitivity was 0.18 (0.13-0.22) and specificity was 0.95 (0.90-0.97).
Conclusions
Our models identify premortem characteristics that can better specify autopsy-defined SAD among presumed SCDs and suggest the World Health Organization definition can be improved by restricting witnessed SCDs to ventricular tachycardia/fibrillation or nonpulseless electrical activity rhythms and unwitnessed cases to <1 hour since last normal, at the cost of sensitivity.



Circ Arrhythm Electrophysiol: 29 Jun 2019; 12:e007171
Tseng ZH, Salazar JW, Olgin JE, Ursell PC, ... Moffatt E, Vittinghoff E
Circ Arrhythm Electrophysiol: 29 Jun 2019; 12:e007171 | PMID: 31248279
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Abstract

Postinfarction Myocardial Calcifications on Cardiac Computed Tomography.

Alyesh DM, Siontis KC, Sharaf Dabbagh G, Yokokawa M, ... Morady F, Bogun F
Background
Postinfarction ventricular tachycardia (VT) generally involves myocardial fibers surrounded by scar. Calcification of scar tissue has been described, but the relationship between calcifications within endocardial scar and VTs is unclear. The purpose of this study was to assess the prevalence of myocardial calcifications as detected by cardiac computed tomography (CT) and the benefit for mapping and ablation focusing on nontolerated VTs.
Methods
Fifty-six consecutive postinfarction patients had a cardiac CT performed before a VT ablation procedure. Another 56 consecutive patients with prior infarction without VT who had cardiac CTs served as a control group.
Results
Myocardial calcifications were identified in 39 of 56 patients (70%) in the postinfarction group with VT, compared with 6 of 56 patients (11%) in the control group without VT. Calcifications were associated with VT when compared with a control group. A calcification volume of 0.538 cm distinguished patients with calcification-associated VT from patients without calcification-associated VTs (area under the curve, 0.87; sensitivity, 0.87; specificity, 0.88). Myocardial calcifications corresponded to areas of electrical nonexcitability and formed a border for reentry circuits for 49 VTs (33% of all VTs for which target sites were identified) in 24 of 39 patients (62%) with myocardial calcifications. A nonconfluent calcification pattern was associated with VT target sites independent of calcification volume ( P=0.01).
Conclusions
Myocardial calcifications detected by cardiac CT in patients with prior infarction are associated with VT. The calcifications correspond to areas of unexcitability and represent a fixed boundary of reentry circuits that can be visualized by CT. Calcifications correspond to effective ablation sites in >1/3 of patients with postinfarction VT.



Circ Arrhythm Electrophysiol: 29 Apr 2019; 12:e007023
Alyesh DM, Siontis KC, Sharaf Dabbagh G, Yokokawa M, ... Morady F, Bogun F
Circ Arrhythm Electrophysiol: 29 Apr 2019; 12:e007023 | PMID: 31006314
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Abstract

Smartwatch Performance for the Detection and Quantification of Atrial Fibrillation.

Wasserlauf J, You C, Patel R, Valys A, Albert D, Passman R

Background Atrial fibrillation (AF) burden and duration appear to be related to stroke risk. A wearable consumer electronic device could provide long-term assessment of these measures inexpensively and noninvasively. This study compares the accuracy of an AF-sensing watch (AFSW; Apple Watch with KardiaBand) with simultaneous recordings from an insertable cardiac monitor (ICM; Reveal LINQ). Methods SmartRhythm 2.0, a convolutional neural network, was trained on anonymized data of heart rate, activity level, and ECGs from 7500 AliveCor users. The network was validated on data collected in 24 patients with ICMs and a history of paroxysmal AF who simultaneously wore the AFSW with SmartRhythm 0.1 software. The primary outcome was sensitivity of the AFSW for AF episodes ≥1 hour. Secondary end points included sensitivity of the AFSW for detection of AF by subject and sensitivity for total AF duration across all subjects. Subjects with >50% false-positive AF episodes on ICM were excluded. Results We analyzed 31 348.9 hours (mean (SD), 11.3 (4.4) hours/day) of simultaneous AFSW and ICM recordings in 24 patients. The ICM detected 82 episodes of AF ≥1 hour while the AFSW was worn, with a total duration of 1127.1 hours. Of these, the SmartRhythm 2.0 neural network detected 80 episodes (episode sensitivity, 97.5%) with a total duration of 1101.1 hours (duration sensitivity, 97.7%). Three of the 18 subjects with AF ≥1 hour had AF only when the watch was not being worn (patient sensitivity, 83.3%; or 100% during time worn). Positive predictive value for AF episodes was 39.9%. Conclusions An AFSW is highly sensitive for detection of AF and assessment of AF duration in an ambulatory population when compared with an ICM. Such devices may represent an inexpensive, noninvasive approach to long-term AF surveillance and management.



Circ Arrhythm Electrophysiol: 30 May 2019; 12:e006834
Wasserlauf J, You C, Patel R, Valys A, Albert D, Passman R
Circ Arrhythm Electrophysiol: 30 May 2019; 12:e006834 | PMID: 31113234
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Abstract

Antiarrhythmic Drugs or Catheter Ablation in the Management of Ventricular Tachyarrhythmias in Patients With Implantable Cardioverter-Defibrillators: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Kheiri B, Barbarawi M, Zayed Y, Hicks M, ... Nazer B, Bhatt DL
Background
In patients with an implantable cardioverter-defibrillator (ICD), shocks are associated with increased morbidity and mortality. Therefore, we conducted this study to evaluate the efficacy and safety of antiarrhythmic drugs and catheter ablation (CA) in the treatment of ventricular tachyarrhythmias (VT) in patients with an ICD.
Methods
An electronic database search for randomized controlled trials that evaluated antiarrhythmic drugs and CA in patients with ICD was conducted. The primary outcome was recurrent VT. Secondary outcomes were ICD shocks and any deaths. Bayesian and frequentist network meta-analyses were performed to calculate hazard ratios (HRs) and 95% credible intervals (CrIs)/CIs.
Results
Twenty-two randomized controlled trials were identified (3828 total patients; age 64.3±11.4; 79% males). The use of amiodarone was associated with a significantly reduced rate of VT recurrence compared with control (HR=0.34 [95% CrI=0.15-0.74]; absolute risk difference=-0.23 [95% CrI=-0.23 to -0.09]; number needed to treat=4). Sotalol was associated with increased risk of VT recurrence compared with amiodarone (HR=2.88 [95% CrI=1.35-6.46]). Compared with control, amiodarone (HR=0.33 [95% CrI=0.15-0.76]; absolute risk difference=-0.17 [95% CrI=-0.32 to -0.06]; number needed to treat=6) and CA (HR=0.52 [95% CrI=0.30-0.89; absolute risk difference=-0.12 [95% CrI=-0.24 to -0.03]; number needed to treat=8) were associated with significantly reduced ICD shocks. Compared with amiodarone, sotalol was associated with significantly increased ICD shocks (HR=2.70 [95% CrI=1.17-6.71]). The rate of death was not significantly different between the competing strategies. The node-splitting method showed no inconsistency.
Conclusions
Among patients with an ICD, amiodarone significantly reduced VT recurrence and ICD shocks, while CA reduced ICD shocks. Sotalol significantly increased VT recurrence and ICD shocks compared with amiodarone. The long-term side effects of amiodarone and early complications of CA should be weighed carefully according to specific patient characteristics.



Circ Arrhythm Electrophysiol: 30 Oct 2019; 12:e007600
Kheiri B, Barbarawi M, Zayed Y, Hicks M, ... Nazer B, Bhatt DL
Circ Arrhythm Electrophysiol: 30 Oct 2019; 12:e007600 | PMID: 31698933
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Abstract

Comparison of the Ventricular Tachycardia Circuit Between Patients With Ischemic and Nonischemic Cardiomyopathies.

Shirai Y, Liang JJ, Santangeli P, Arkles JS, ... Marchlinski FE, Frankel DS
Background
There has been increasing awareness of the 3-dimensional nature of ventricular tachycardia (VT) circuits. VT circuits in patients with ischemic cardiomyopathies (ICM) and non-ICM (NICM) may differ in this regard.
Methods
Among patients with structural heart disease and at least 1 hemodynamically tolerated VT undergoing ablation, we retrospectively analyzed responses to all entrainment maneuvers.
Results
Of 445 patients (ICM 228, NICM 217) undergoing VT ablation, detailed entrainment mapping of at least 1 tolerated VT was performed in 111 patients (ICM 71, NICM 40). Of 89 ICM VTs, the isthmus could be identified by endocardial entrainment in 55 (62%), compared with only 8 of 47 (17%) NICM VTs ( P<0.01). With combined endocardial and epicardial mapping, the isthmus could be identified in 56 (63%) ICM VTs and 12 (26%) NICM VTs ( P<0.01), whereas any critical component (defined as entrance, isthmus or exit) could be identified in 76 (85%) ICM VTs and 37 (79%) NICM VTs ( P=0.3). Complete success (no inducible VT at the end of ablation, 82% versus 65%, P=0.04) and 1-year, single-procedure VT-free survival (82% versus 55%, P<0.01) were both higher among patients with ICM.
Conclusions
Among mappable ICM VTs, critical circuit components can usually be identified on the endocardium. In contrast, among mappable NICM VTs, although some critical component can typically be identified with the addition of epicardial mapping, the isthmus is less commonly identified, possibly due to midmyocardial location.



Circ Arrhythm Electrophysiol: 29 Jun 2019; 12:e007249
Shirai Y, Liang JJ, Santangeli P, Arkles JS, ... Marchlinski FE, Frankel DS
Circ Arrhythm Electrophysiol: 29 Jun 2019; 12:e007249 | PMID: 31296041
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Abstract

Simultaneous Comparison of Electrocardiographic Imaging and Epicardial Contact Mapping in Structural Heart Disease.

Graham AJ, Orini M, Zacur E, Dhillon G, ... Hunter RJ, Lambiase PD
Background
The accuracy of ECG imaging (ECGI) in structural heart disease remains uncertain. This study aimed to provide a detailed comparison of ECGI and contact-mapping system (CARTO) electrograms.
Methods
Simultaneous epicardial mapping using CARTO (Biosense-Webster, CA) and ECGI (CardioInsight) in 8 patients was performed to compare electrogram morphology, activation time (AT), and repolarization time (RT). Agreement between AT and RT from CARTO and ECGI was assessed using Pearson correlation coefficient, ρand ρ , root mean square error, Eand E , and Bland-Altman plots.
Results
After geometric coregistration, 711 (439-905; median, first-third quartiles) ECGI and CARTO points were paired per patient. AT maps showed ρ =0.66 (0.53-0.73) and E =24 (21-32) ms, RT maps showed ρ =0.55 (0.41-0.71) and E =51 (38-70) ms. The median correlation coefficient measuring the morphological similarity between the unipolar electrograms was equal to 0.71 (0.65-0.74) for the entire signal, 0.67 (0.59-0.76) for QRS complexes, and 0.57 (0.35-0.76) for T waves. Local activation map correlation, ρ , was lower when default filters were used (0.60 (0.30-0.71), P=0.053). Small misalignment of the ECGI and CARTO geometries (below ±4 mm and ±4°) could introduce variations in the median ρup to ±25%. Minimum distance between epicardial pacing sites and the region of earliest activation in ECGI was 13.2 (0.0-28.3) mm from 25 pacing sites with stimulation to QRS interval <40 ms.
Conclusions
This simultaneous assessment demonstrates that ECGI maps activation and repolarization parameters with moderate accuracy. ECGI and contact electrogram correlation is sensitive to electrode apposition and geometric alignment. Further technological developments may improve spatial resolution.



Circ Arrhythm Electrophysiol: 30 Mar 2019; 12:e007120
Graham AJ, Orini M, Zacur E, Dhillon G, ... Hunter RJ, Lambiase PD
Circ Arrhythm Electrophysiol: 30 Mar 2019; 12:e007120 | PMID: 30947511
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Abstract

SNX17 (Sorting Nexin 17) Mediates Atrial Fibrillation Onset Through Endocytic Trafficking of the Kv1.5 (Potassium Voltage-Gated Channel Subfamily A Member 5) Channel.

Geng L, Wang S, Zhang F, Xiong K, ... Xie D, Chen YH
Background
Kv1.5 (Potassium voltage-gated channel subfamily A member 5) has been regarded as a promising target of interventions for atrial fibrillation (AF). SNX17 (sorting nexin 17), a member of the SNXs (sorting nexin family), regulates the intracellular trafficking of membrane proteins through its FERM (four-point-one, ezrin, radixin, moesin) domain. However, whether SNX17 regulates the trafficking process of Kv1.5 remains unknown.
Methods
A SNX17 knockout rat line was generated to test the role of SNX17 in atrial electrophysiology. The protein expression of SNX17 and membrane ion channels was detected by Western blotting. Electrophysiology changes in the atrial tissue and myocytes were analyzed by optical mapping and patch clamp, respectively. Acetylcholine and electrical stimulation were used to induce AF, and ECG recording was adopted to assess the influence of SNX17 deficiency on AF susceptibility. The spatial relationship between Kv1.5 and SNX17 was evaluated by immunostaining and confocal scanning, and the functional region of SNX17 regulating Kv1.5 trafficking was identified using plasmids with truncated SNX17 domains.
Results
Embryonic death occurred in homozygous SNX17 knockout rats. SNX17 heterozygous rats survived, and the level of the SNX17 protein in the atrium was decreased by ≈50%. SNX17 deficiency increased the membrane expression of Kv1.5 and atria-specific ultrarapid delayed rectifier outward potassium current ( I) density, resulting in a shortened action potential duration, and eventually contributing to AF susceptibility. Mechanistically, SNX17 facilitated the endocytic sorting of Kv1.5 from the plasma membrane to early endosomes via the FERM domain.
Conclusions
SNX17 mediates susceptibility to AF by regulating endocytic sorting of the Kv1.5 channel through the FERM domain. SNX17 could be a potential target for the development of new drugs for AF.



Circ Arrhythm Electrophysiol: 30 Mar 2019; 12:e007097
Geng L, Wang S, Zhang F, Xiong K, ... Xie D, Chen YH
Circ Arrhythm Electrophysiol: 30 Mar 2019; 12:e007097 | PMID: 30939909
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Abstract

Atrial Fibrillation Catheter Ablation Increases the Left Atrial Pressure.

Park JW, Yu HT, Kim TH, Uhm JS, ... Hwang C, Pak HN
Background
We previously reported that a high left atrial (LA) pressure is associated with LA stiffness and poor rhythm outcomes after de novo catheter ablation of atrial fibrillation. Herein, we investigated whether radiofrequency catheter ablation generally changes the LA pressure among patients undergoing repeat procedures.
Methods
Among 1848 patients who underwent atrial fibrillation catheter ablation, we measured the LA pressure during sinus rhythm in 1687 patients before the de novo ablation (59±11 years, 72.4% men, 72.8% paroxysmal atrial fibrillation) and in 142 with second procedures. We measured the LA pressure immediately after the transseptal puncture at the beginning of the procedure.
Results
In the same 142 patients, the degree of LA stiffness, reflected by the LA pulse pressure (LA), was significantly higher in the second procedure than in the de novo procedure ( P<0.001). The degree of the LA increase (ΔLA) was significantly higher in patients who underwent additional extrapulmonary vein LA ablation than in those who underwent circumferential pulmonary vein isolation alone ( P=0.010). Extrapulmonary vein LA ablation was independently associated with the ΔLA (β=5.70 [0.12-11.27]; P=0.045). An increased LA during repeat procedures was independently associated with a reduced diastolic function (β=2.01 [0.08-3.93]; P=0.041) without a worsening symptoms (EuroQol-five dimensions) score, 22.2±17.9 months after the de novo ablation.
Conclusions
Atrial fibrillation catheter ablation, especially extrapulmonary vein LA ablation, increased the LA stiffness and was associated with a worsening postablation diastolic function. However, the symptom score did not significantly change.
Clinical trial registration
URL: https://www.clinicaltrials.gov . Unique identifier: NCT02138695.



Circ Arrhythm Electrophysiol: 30 Mar 2019; 12:e007073
Park JW, Yu HT, Kim TH, Uhm JS, ... Hwang C, Pak HN
Circ Arrhythm Electrophysiol: 30 Mar 2019; 12:e007073 | PMID: 30917688
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Abstract

Real-time Electrogram Analysis for Drivers of AtRial Fibrillation (RADAR): A Multi-Center FDA-IDE Clinical Trial of Persistent AF.

Choudry S, Mansour M, Sundaram S, Nguyen DT, ... Kessman P, Reddy VY

- Pulmonary vein isolation (PVI) is insufficient to treat all patients with persistent atrial fibrillation (AF), and effective adjunctive ablation strategies are needed. Ablation of AF drivers holds promise, but current technologies to identify drivers are limited by spatial resolution. In a single-arm, first-in-human, investigator-initiated FDA IDE study, we employed a novel system for real-time, high-resolution identification of AF drivers in persistent AF.- Persistent or longstanding persistent AF patients underwent ablation using the RADAR system in conjunction with a standard electroanatomical mapping system. After PVI, electrogram and spatial information was streamed and analyzed to identify driver domains to target for ablation.- Across 4 centers, 64 subjects were enrolled: 73% male, age 64.7±9.5 years, BMI 31.7±6.0 kg/m, LA size 54±10 mm, with persistent/longstanding persistent AF in 53 (83%) / 11 (17%), prior AF ablation (re-do group) in 26 (41%). After 12.6 ±} 0.8 months follow-up, 68% remained AF-free off all antiarrhythmics; 74% remained AF-free and 66% remained AF/AT/AFL-free on or off antiarrhythmic drugs. AF terminated with ablation in 35 patients (55%) overall and in 23/38 (61%) of de novo ablation patients. For patients with AF termination during ablation, 82% remained AF-free and 74% AF/AT/AFL free during follow-up on or off antiarrhythmic drugs. Patients undergoing first-time ablation generally had higher rates of freedom from AF than the re-do group.- This novel technology for panoramic mapping of AF drivers showed promising results in a persistent/long-standing persistent AF population. These data provide the scientific basis for a randomized trial.- clinicaltrials.org; Unique Identifier: NCT03263702; IDE#G170049.



Circ Arrhythm Electrophysiol: 15 Jan 2020; epub ahead of print
Choudry S, Mansour M, Sundaram S, Nguyen DT, ... Kessman P, Reddy VY
Circ Arrhythm Electrophysiol: 15 Jan 2020; epub ahead of print | PMID: 31944826
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Abstract

Left Ventricular Remodeling Results in Homogenization of Myocardial Work Distribution.

Duchenne J, Turco A, Ünlü S, Pagourelias ED, ... Gheysens O, Voigt JU
Background
The interaction between regional left ventricular (LV) myocardial work and metabolism in remodeled hearts has not yet been well established. Our aim was to investigate the effect of inhomogeneous LV work distribution on regional metabolism and remodeling in our animal model with reversible dyssynchrony due to pacing.
Methods
In 12 sheep, 8 weeks of right atrial and right ventricular free wall (DDD) pacing lead to LV dilatation, a thinned septum, and thickened lateral wall. Left bundle branch block-like dyssynchrony caused by DDD pacing could be acutely reverted by right atrial pacing (AAI) only. Invasive hemodynamics and echocardiography were used to assess regional work by stress-strain loop area and compared with regional glucose metabolism measured by F-fluorodeoxyglucose positron emission tomography with and without improved spatial resolution by motion and anatomy correction on gated reconstructions.
Results
Glucose metabolism by positron emission tomography with anatomic correction on gated positron emission tomography reconstruction showed a different regional distribution than with clinical reconstructions and correlated best and significantly with regional myocardial work. At baseline, work was homogeneously distributed with normal conduction (AAI pacing), whereas during dyssynchrony (DDD pacing), the lateral wall was more loaded, and the septum was unloaded. After 8 weeks of remodeling under DDD pacing, however, an almost homogeneous work distribution was found with DDD pacing, whereas with AAI pacing, the thin septum showed exaggerated loading and the lateral walls a low load. Our experimental observations were confirmed in 5 patient responders to cardiac resynchronization therapy.
Conclusions
Regional LV glucose metabolism closely correlates with regional work. Our data indicate that regionally different LV remodeling after exposure to inhomogeneous loading conditions, such as during LV dyssynchrony, is an adaptive process that helps to equilibrate work distribution. Correction of the inhomogeneous loading conditions, such as during cardiac resynchronization therapy, then triggers a reverse LV remodeling through the same mechanism.



Circ Arrhythm Electrophysiol: 29 Apr 2019; 12:e007224
Duchenne J, Turco A, Ünlü S, Pagourelias ED, ... Gheysens O, Voigt JU
Circ Arrhythm Electrophysiol: 29 Apr 2019; 12:e007224 | PMID: 31023060
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Abstract

Major Adverse Cardiovascular Events Associated with Post-Operative Atrial Fibrillation after Non-Cardiac Surgery: A Systematic Review and Meta-analysis.

AlTurki A, Marafi M, Proietti R, Cardinale D, ... Healey JS, Huynh T

- Post-operative atrial fibrillation (POAF) is a frequent occurrence after non-cardiac surgery. It remains unclear whether POAF is associated with an increased risk of major adverse events. We aimed to elucidate the risk of stroke, myocardial infarction and death associated with POAF following non-cardiac surgery by a meta-analysis of randomized controlled studies and observational studies.- We searched electronic databases from inception up to August 1st, 2019 for all studies that reported stroke or myocardial infarction in adult patients who developed POAF following non-cardiac surgery. We used random-effects models to summarize the studies.- The final analyses included 28 studies enrolling 2,612,816 patients. At one-month (ten studies), POAF was associated with an approximately three-fold increase in the risk of stroke (weighted mean 2.1% vs 0.7%) [odds ratio (OR) 2.82 (95% Confidence intervals (CI): 2.15-3.70); p< 0.001]. POAF was associated with approximately four-fold increase in the long-term risk of stroke with (weighted mean 2.0% vs 0.6%) (OR 4.12, 95% CI: 3.32-5.11; pȦ4;0.001) in eight studies with Ȧ5;12-month follow-up. There was a significant overall increase in the risk of stroke and myocardial infarction associated with POAF (weighted mean 2.5% vs 0.9%) (OR 3.44,95% CI: 2.38-4.98; p<0.001) and (weighted mean 12.6% vs 2.7%) (OR 4.02, 95% CI: 3.08-5.24; p<0.001) respectively. Furthermore, POAF was associated with a three-fold increase in all-cause mortality at 30 days (weighted mean 15.0% vs 5.4%) (OR: 3.36; 95% CI: 2.13-5.31; p<0.001).- POAF was associated with markedly higher risk of stroke, myocardial infarction and all-cause mortality following non-cardiac surgery. Future studies are needed to evaluate the impact of optimal cardiovascular pharmacotherapies to prevent POAF and to decrease the risk of major adverse events in these high-risk patients.



Circ Arrhythm Electrophysiol: 15 Jan 2020; epub ahead of print
AlTurki A, Marafi M, Proietti R, Cardinale D, ... Healey JS, Huynh T
Circ Arrhythm Electrophysiol: 15 Jan 2020; epub ahead of print | PMID: 31944855
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Abstract

Differentiating Right- and Left-Sided Outflow Tract Ventricular Arrhythmias.

Anderson RD, Kumar S, Parameswaran R, Wong G, ... Kalman J, Lee G

Idiopathic ventricular arrhythmias commonly originate from the right ventricular and left ventricular outflow tracts (OTs). Advances in real-time imaging have refined our understanding of the intimate anatomic structures implicated in the genesis of OT arrhythmias, making catheter ablation for arrhythmias beyond the right ventricular OT a feasible option for cure-indeed ablation is now a class I indication in recent guidelines. The surface 12-lead ECG is routinely used to localize the anatomic site of origin before catheter ablation. However, the intimate and complex anatomy of the OT limits predictive value ECG criteria alone for localization for these arrhythmias. Multiple ECG algorithms have been developed to assist preprocedural localization, and hence predict safety and efficacy for catheter ablation of OT ventricular arrhythmias. This review will summarize all of the published 12-lead ECG algorithms used to guide localization of OT ventricular arrhythmias.



Circ Arrhythm Electrophysiol: 30 May 2019; 12:e007392
Anderson RD, Kumar S, Parameswaran R, Wong G, ... Kalman J, Lee G
Circ Arrhythm Electrophysiol: 30 May 2019; 12:e007392 | PMID: 31159581
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Abstract

Importance of Diastolic Function for the Prediction of Arrhythmic Death: A Prospective, Observer Blinded, Long-term Study.

Pezawas T, Burger AL, Binder T, Diedrich A

- Patients with ischemic or dilated cardiomyopathy and reduced left ventricular ejection fraction (LVEF) face a high risk for ventricular arrhythmias. Exact grading of diastolic function might improve risk stratification for arrhythmic death.- We prospectively enrolled 120 patients with ischemic, 60 patients with dilated cardiomyopathy and 30 patients with normal LVEF. Diastolic function was graded normal (N) or dysfunction grade I-III. Primary outcome parameter was arrhythmic death (AD) or resuscitated cardiac arrest (RCA).- Normal diastolic function was found in 23 (11%) patients, dysfunction grade I in 107 (51%), grade II in 31 (14.8%) and grade III in 49 (23.3%) patients, respectively. After an average follow-up of 7.0±2.6 years, AD or RCA was observed in 28 (13.3%) and 33 (15.7%) patients, respectively. Non-arrhythmic death was found in 41 (19.5%) patients. On Kaplan-Meier analysis, patients with dysfunction grade III had the highest risk for AD or RCA (p<0.001). This finding was independent from the degree of LVEF dysfunction and was observed in patients with LVEFȦ4;35% (p=0.001) and with LVEF>35% (p=0.014). Non-arrhythmic mortality was highest in patients with dysfunction grade III. This was true for patients with LVEFȦ4;35% (p=0.009) or >35% (p<0.001). In an adjusted model for relevant confounding factors, grade III dysfunction was associated with a 3.5-fold increased risk for AD or RCA in the overall study population (HR=3.52, p<0.001).- Diastolic dysfunction is associated with a high risk for AD or RCA regardless if LVEF is Ȧ4;35% or >35%. Diastolic function grading might improve risk stratification for AD.



Circ Arrhythm Electrophysiol: 15 Jan 2020; epub ahead of print
Pezawas T, Burger AL, Binder T, Diedrich A
Circ Arrhythm Electrophysiol: 15 Jan 2020; epub ahead of print | PMID: 31944144
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Abstract

Expandable Lattice Electrode Ablation Catheter.

Barkagan M, Leshem E, Rottmann M, Sroubek J, Shapira-Daniels A, Anter E
Background
High-current short-duration radiofrequency energy delivery has potential advantages for cardiac ablation. However, this strategy is limited by high current density and narrow safety-to-efficacy window. The objective of this study was to examine a novel strategy for radiofrequency energy delivery using a new electrode design capable of delivering high power at a low current density to increase the therapeutic range of radiofrequency ablation.
Methods
The Sphere9 is an expandable spheroid-shaped lattice electrode design with an effective surface area 10-fold larger than standard irrigated electrodes (lattice catheter). It incorporates 9 surface temperature sensors with ablation performed in a temperature-controlled mode. Phase I: in 6 thigh muscle preparations, 2 energy settings for atrial ablation were compared between the lattice and irrigated-tip catheters (low-energy: T75°C/5 s versus 25 W/20 s; high-energy: T75°C/7 s versus 30 W/20 s). Phase II: in 8 swine, right atrial lines were created in the posterior and lateral walls using low- and high-energy settings, respectively. Phase III: the safety, efficacy, and durability at 30 days were evaluated by electroanatomical mapping and histopathologic analysis.
Results
In the thigh model, the lattice catheter resulted in wider lesions at both low- and high-energy settings (18.7±3.3 versus 12.2±1.7 mm, P<0.0001; 19.4±2.4 versus 12.3±1.7 mm, P<0.0001). Atrial lines created with the lattice were wider (posterior: 14.7±3.4 versus 9.2±4.0 mm, P<0.0001; lateral: 15.8±4.2 versus 5.7±4.2 mm, P<0.0001) and required 85% shorter ablation time (12.4 versus 79.8 s/cm-line). While current squared (I) was higher with Sphere9 (7.0±0.04 versus 0.2±0.002 A; P<0.0001), the current density was lower (9.6±0.9 versus 16.9±0.09 mA/mm; P<0.0001). At 30 days, 100% of ablation lines created with the lattice catheter remained contiguous compared with only 14.3% lines created with a standard irrigated catheter. This was achieved without steam pops or collateral tissue damage.
Conclusions
In this preclinical model, a novel, high-current low-density radiofrequency ablation strategy created contiguous and durable ablation lines in significantly less ablation time and a comparable safety profile.



Circ Arrhythm Electrophysiol: 30 Mar 2019; 12:e007090
Barkagan M, Leshem E, Rottmann M, Sroubek J, Shapira-Daniels A, Anter E
Circ Arrhythm Electrophysiol: 30 Mar 2019; 12:e007090 | PMID: 30943762
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Abstract

Familial Clustering of Cardiac Conduction Defects and Pacemaker Insertion.

Kaess BM, Andersson C, Duncan MS, Larson MG, ... Torp-Pedersen C, Vasan RS
Background
The etiopathogenesis of electrocardiographic bundle branch and atrioventricular blocks is not fully understood. We investigated familial clustering of cardiac conduction defects and pacemaker insertion in the FHS (Framingham Heart Study). Additionally, we assessed familial clustering of pacemaker insertion in the Danish general population.
Methods
In FHS, we used multivariable-adjusted logistic regression models to investigate the association of parental atrioventricular block (PR interval, ≥0.2 s), complete bundle branch block (QRS, ≥0.12 s), or pacemaker insertion with the occurrence of cardiac conduction abnormalities in their offspring. The Danish nationwide administrative registries were interrogated to assess the relations of parental pacemaker insertion with offspring pacemaker insertion.
Results
In FHS (n=371 cases with first-degree atrioventricular block, complete bundle branch block, or pacemaker insertion, and 1471 age- and sex-matched controls), individuals with at least 1 affected parent with a conduction defect had a 1.65-fold odds (odds ratio, 95% CI, 1.32-2.07) for manifesting an atrioventricular block and a 1.62-fold odds (95% CI, 1.08-2.42) for developing a complete bundle branch block. If at least 1 parent had any electrocardiographic conduction defect or pacemaker insertion, the offspring had a 1.62-fold odds (95% CI, 1.31-2.00) for experiencing any of these conditions. In Denmark (n=2 824 199 individuals; 5397 incident pacemaker implantations), individuals with at least 1 first-degree relative with history of pacemaker insertion had a multivariable-adjusted 1.68-fold (incidence rate ratio, 95% CI, 1.49-1.89) risk of undergoing a pacemaker insertion. If the affected relative was ≤45 years of age, the incidence rate ratio was markedly increased to 51.0 (95% CI, 32.7-79.9).
Conclusions
Cardiac conduction blocks and risk for pacemaker insertion cluster within families. A family history of conduction system disturbance or pacemaker insertion should trigger increased awareness of a similar propensity in other family members, especially so when the conduction system disease occurs at a younger age.



Circ Arrhythm Electrophysiol: 29 Jun 2019; 12:e007150
Kaess BM, Andersson C, Duncan MS, Larson MG, ... Torp-Pedersen C, Vasan RS
Circ Arrhythm Electrophysiol: 29 Jun 2019; 12:e007150 | PMID: 31216886
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Abstract

Cardiac Afferent Denervation Abolishes Ganglionated Plexi and Sympathetic Responses to Apnea.

Tavares L, Rodríguez-Mañero M, Kreidieh B, Ibarra-Cortez SH, ... Barrios R, Valderrábano M

Background The autonomic nervous system response to apnea and its mechanistic connection to atrial fibrillation (AF) are unclear. We hypothesize that sensory neurons within the ganglionated plexi (GP) play a role. We aimed to delineate the autonomic response to apnea and to test the effects of ablation of cardiac sensory neurons with resiniferatoxin (RTX), a neurotoxic TRPV1 (transient receptor potential vanilloid 1) agonist. Methods Sixteen dogs were anesthetized and ventilated. Apnea was induced by stopping ventilation until oxygen saturations decreased to 80%. Nerve recordings from bilateral vagal nerves, left stellate ganglion, and anterior right GP were obtained before and during apnea, before and after RTX injection in the anterior right GP (protocol 1, n=7). Atrial effective refractory period and AF inducibility on single extrastimulation were assessed before and during apnea, and before and after intrapericardial RTX administration (protocol 2, n=9). GPs underwent immunohistochemical staining for TRPV1. Results Apnea increased anterior right GP activity, followed by clustered crescendo vagal bursts synchronized with heart rate and blood pressure oscillations. On further oxygen desaturation, a tonic increase in stellate ganglion activity and blood pressure ensued. Apnea-induced effective refractory period shortening from 110.20±31.3 ms to 90.6±29.1 ms ( P<0.001), and AF induction in 9/9 dogs versus 0/9 at baseline. After RTX administration, increases in GP and stellate ganglion activity and blood pressure during apnea were abolished, effective refractory period increased to 126.7±26.9 ms ( P=0.0001), and AF was not induced. Vagal bursts remained unchanged. GP cells showed cytoplasmic microvacuolization and apoptosis. Conclusions Apnea increases GP activity, followed by vagal bursts and tonic stellate ganglion firing. RTX decreases sympathetic and GP nerve activity, abolishes apnea\'s electrophysiological response, and AF inducibility. Sensory neurons play a role in apnea-induced AF.



Circ Arrhythm Electrophysiol: 30 May 2019; 12:e006942
Tavares L, Rodríguez-Mañero M, Kreidieh B, Ibarra-Cortez SH, ... Barrios R, Valderrábano M
Circ Arrhythm Electrophysiol: 30 May 2019; 12:e006942 | PMID: 31164004
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Abstract

Local Conduction Velocity in the Presence of Late Gadolinium Enhancement and Myocardial Wall Thinning.

Jang J, Whitaker J, Leshem E, Ngo LH, ... Anter E, Nezafat R
Background
Conduction velocity (CV) is an important property that contributes to the arrhythmogenicity of the tissue substrate. The aim of this study was to investigate the association between local CV versus late gadolinium enhancement (LGE) and myocardial wall thickness in a swine model of healed left ventricular infarction.
Methods
Six swine with healed myocardial infarction underwent cardiovascular magnetic resonance imaging and electroanatomic mapping. Two healthy controls (one treated with amiodarone and one unmedicated) underwent electroanatomic mapping with identical protocols to establish the baseline CV. CV was estimated using a triangulation technique. LGE+ regions were defined as signal intensity >2 SD than the mean of remote regions, wall thinning+ as those with wall thickness <2 SD than the mean of remote regions. LGE heterogeneity was defined as SD of LGE in the local neighborhood of 5 mm and wall thickness gradient as SD within 5 mm. Cardiovascular magnetic resonance and electroanatomic mapping data were registered, and hierarchical modeling was performed to estimate the mean difference of CV (LGE+/-, wall thinning+/-), or the change of the mean of CV per unit change (LGE heterogeneity, wall thickness gradient).
Results
Significantly slower CV was observed in LGE+ (0.33±0.25 versus 0.54±0.36 m/s; P<0.001) and wall thinning+ regions (0.38±0.28 versus 0.55±0.37 m/s; P<0.001). Areas with greater LGE heterogeneity ( P<0.001) and wall thickness gradient ( P<0.001) exhibited slower CV.
Conclusions
Slower CV is observed in the presence of LGE, myocardial wall thinning, high LGE heterogeneity, and a high wall thickness gradient. Cardiovascular magnetic resonance may offer a valuable imaging surrogate for estimating CV, which may support noninvasive identification of the arrhythmogenic substrate.



Circ Arrhythm Electrophysiol: 29 Apr 2019; 12:e007175
Jang J, Whitaker J, Leshem E, Ngo LH, ... Anter E, Nezafat R
Circ Arrhythm Electrophysiol: 29 Apr 2019; 12:e007175 | PMID: 31006313
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Abstract

Evaluating Real-World Clinical Outcomes in Atrial Fibrillation Patients Receiving the WATCHMAN Left Atrial Appendage Closure Technology.

Boersma LV, Ince H, Kische S, Pokushalov E, ... Bergmann MW,
Background
Left atrial appendage occlusion with WATCHMAN has emerged as viable alternative to vitamin K antagonists in randomized controlled trials. Evaluating real-life clinical outcomes in atrial fibrillation patients receiving the WATCHMAN left atrial appendage closure technology was designed to collect prospective multicenter outcomes of thromboembolic events, bleeding, and mortality for patients implanted with a WATCHMAN in routine daily practice.
Methods
One thousand twenty patients with a WATCHMAN implant procedure were prospectively followed in 47 centers. Left atrial appendage occlusion indication was based on the European Society of Cardiology guidelines. Follow-up and imaging were performed per local practice up to a median follow-up of 2 years.
Results
Included population was old (age 73.4±8.9 years), at high risk for stroke (311 prior ischemic stroke/transient ischemic attack and 153 prior hemorrhagic stroke) and bleeding (318 prior major bleeding), with CHADS-VASc score ≥5 in 49%, hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, Labile international normalized ratio, elderly, drugs/alcohol concomitantly ≥3 in 40% and oral anticoagulation contraindication in 72%. During follow-up, 161 patients (16.4%) died, 22 strokes were observed (1.3/100 patient-years, 83% reduction versus historic data), and 47 major nonprocedural bleeding events (2.7/100 patient-years, 46% reduction versus historic data). Stroke and bleeding rates were consistently lower than historic data in those with prior ischemic (-76% and -41%) or hemorrhagic (-81% and 67%) stroke and prior bleeding (-85% and -30%). Lowest bleeding rates were seen in patients with early discontinuation of dual antiplatelet therapy. Patients with early discontinuation of antithrombotic therapy showed lower bleeding rates, while they were highest for those with prior bleeding. Device thrombus was observed in 34 patients (4.1%) and was not correlated to drug regimen during follow-up ( P=0.28).
Conclusions
During the complete 2-year follow-up of Evaluating Real-Life Clinical Outcomes in Atrial Fibrillation Patients Receiving the WATCHMAN Left Atrial Appendage Closure Technology, patients with a WATCHMAN left atrial appendage occlusion device had consistently low rates of stroke and nonprocedural bleeding, although most were contraindicated to oral anticoagulation and used only single antiplatelet therapy or nothing.
Clinical trial registration
URL: https://clinicaltrials.gov . Unique identifier: NCT01972282.



Circ Arrhythm Electrophysiol: 30 Mar 2019; 12:e006841
Boersma LV, Ince H, Kische S, Pokushalov E, ... Bergmann MW,
Circ Arrhythm Electrophysiol: 30 Mar 2019; 12:e006841 | PMID: 30939908
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Abstract

HDAC (Histone Deacetylase) Inhibitor Valproic Acid Attenuates Atrial Remodeling and Delays the Onset of Atrial Fibrillation in Mice.

Scholz B, Schulte JS, Hamer S, Himmler K, ... Völker U, Müller FU
Background
A structural, electrical and metabolic atrial remodeling is central in the development of atrial fibrillation (AF) contributing to its initiation and perpetuation. In the heart, HDACs (histone deacetylases) control remodeling associated processes like hypertrophy, fibrosis, and energy metabolism. Here, we analyzed, whether the HDAC class I/IIa inhibitor valproic acid (VPA) is able to attenuate atrial remodeling in CREM-IbΔC-X (cAMP responsive element modulator isoform IbΔC-X) transgenic mice, a mouse model of extensive atrial remodeling with age-dependent progression from spontaneous atrial ectopy to paroxysmal and finally long-lasting AF.
Methods
VPA was administered for 7 or 25 weeks to transgenic and control mice. Atria were analyzed macroscopically and using widefield and electron microscopy. Action potentials were recorded from atrial cardiomyocytes using patch-clamp technique. ECG recordings documented the onset of AF. A proteome analysis with consecutive pathway mapping identified VPA-mediated proteomic changes and related pathways.
Results
VPA attenuated many components of atrial remodeling that are present in transgenic mice, animal AF models, and human AF. VPA significantly ( P<0.05) reduced atrial dilatation, cardiomyocyte enlargement, atrial fibrosis, and the disorganization of myocyte\'s ultrastructure. It significantly reduced the occurrence of atrial thrombi, reversed action potential alterations, and finally delayed the onset of AF by 4 to 8 weeks. Increased histone H4-acetylation in atria from VPA-treated transgenic mice verified effective in vivo HDAC inhibition. Cardiomyocyte-specific genetic inactivation of HDAC2 in transgenic mice attenuated the ultrastructural disorganization of myocytes comparable to VPA. Finally, VPA restrained dysregulation of proteins in transgenic mice that are involved in a multitude of AF relevant pathways like oxidative phosphorylation or RhoA (Ras homolog gene family, member A) signaling and disease functions like cardiac fibrosis and apoptosis of muscle cells.
Conclusions
Our results suggest that VPA, clinically available, well-tolerated, and prescribed to many patients for years, has the therapeutic potential to delay the development of atrial remodeling and the onset of AF in patients at risk.



Circ Arrhythm Electrophysiol: 27 Feb 2019; 12:e007071
Scholz B, Schulte JS, Hamer S, Himmler K, ... Völker U, Müller FU
Circ Arrhythm Electrophysiol: 27 Feb 2019; 12:e007071 | PMID: 30879335
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Abstract

Lesion Index Titration Using Contact-Force Technology Enables Safe and Effective Radiofrequency Lesion Creation at the Root of the Aorta and Pulmonary Artery.

Alfonso-Almazán JM, Quintanilla JG, García-Torrent MJ, Laguna-Castro S, ... Perez-Villacastín J, Filgueiras-Rama D
Background
Ablation of some myocardial substrates requires catheter-based radiofrequency delivery at the root of a great artery. We studied the safety and efficacy parameters associated with catheter-based radiofrequency delivery at the root of the aorta and pulmonary artery.
Methods
Thirty-six pigs underwent in-vivo catheter-based ablation under continuous contact-force and lesion index (power, contact-force, and time) monitoring during 60-s radiofrequency delivery with an open-irrigated tip catheter. Twenty-eight animals were allocated to groups receiving 40 W (n=9), 50 W (n=10), or 60 W (n=9) radiofrequency energy, and acute (n=22) and chronic (n=6) arterial wall damage was quantified by multiphoton microscopy in ex vivo samples. Adjacent myocardial lesions were quantified in parallel samples. The remaining 8 pigs were used to validate safety and efficacy parameters.
Results
Acute collagen and elastin alterations were significantly associated with radiofrequency power, although chronic assessment revealed vascular wall recovery in lesions without steam pop. The main parameters associated with steam pops were median peak temperature >42°C and impedance falls >23 ohms. Unlike other parameters, lesion index values of 9.1 units (interquartile range, 8.7-9.8) were associated with the presence of adjacent myocardial lesions in both univariate ( P=0.03) and multivariate analyses ( P=0.049; odds ratio, 1.99; 95% CI, 1.02-3.98). In the validation group, lesion index values using 40 W over a range of contact-forces correlated with the size of radiofrequency lesions (R=0.57; P=0.03), with no angiographic or histopathologic signs of coronary artery damage.
Conclusions
Lesion index values obtained during 40 W radiofrequency applications reliably monitor safe and effective lesion creation at the root of the great arteries.



Circ Arrhythm Electrophysiol: 27 Feb 2019; 12:e007080
Alfonso-Almazán JM, Quintanilla JG, García-Torrent MJ, Laguna-Castro S, ... Perez-Villacastín J, Filgueiras-Rama D
Circ Arrhythm Electrophysiol: 27 Feb 2019; 12:e007080 | PMID: 30879334
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Abstract

Glycemic Status and Thromboembolic Risk in Patients With Atrial Fibrillation and Type 2 Diabetes Mellitus.

Fangel MV, Nielsen PB, Kristensen JK, Larsen TB, ... Lip GYH, Jensen MB

Background Diabetes mellitus is associated with increased risk of stroke in patients with atrial fibrillation, and differences in glycemic status may affect this risk. We aimed to examine the effect of glycemic status evaluated by hemoglobin A1c (HbA1c) on the risk of thromboembolism among patients with atrial fibrillation and type 2 diabetes mellitus. Methods In this cohort study, we used data from Danish registries to identify patients with type 2 diabetes mellitus and incident nonvalvular atrial fibrillation in the period of May 1, 2005, through December 31, 2015. On the basis of the most recent HbA1c measurement before an incident atrial fibrillation diagnosis, patients were divided into the categories: HbA1c ≤48 mmol/mol, HbA1c=49-58 mmol/mol, and HbA1c >58 mmol/mol. Cox regression analysis was used to estimate hazard ratios for the outcome thromboembolism. Results The study population included 5386 patients with incident nonvalvular atrial fibrillation and type 2 diabetes mellitus. Compared with patients with HbA1c ≤48 mmol/mol, we observed a higher risk of thromboembolism among patients with HbA1c=49-58 mmol/mol (hazard ratio, 1.49; 95% CI, 1.09-2.05) and HbA1c >58 mmol/mol (hazard ratio, 1.59; 95% CI, 1.13-2.22) after adjusting for confounding factors. When stratified on diabetes mellitus duration, similar results were found among patients with diabetes mellitus duration of <10 years. Contrastingly, in patients with diabetes mellitus duration of ≥10 years, higher HbA1c levels were not associated with a higher risk of thromboembolism. Conclusions In patients with incident atrial fibrillation and type 2 diabetes mellitus, increasing levels of HbA1c were associated with a higher risk of thromboembolism. However, no association was found among patients with diabetes mellitus duration ≥10 years.



Circ Arrhythm Electrophysiol: 29 Apr 2019; 12:e007030
Fangel MV, Nielsen PB, Kristensen JK, Larsen TB, ... Lip GYH, Jensen MB
Circ Arrhythm Electrophysiol: 29 Apr 2019; 12:e007030 | PMID: 30995869
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Abstract

Targeting Noninducible Clinical Ventricular Tachycardias in Patients With Prior Myocardial Infarctions Based on Stored Electrograms.

Yokokawa M, Kim HM, Sharaf Dabbagh G, Siontis KC, ... Morady F, Bogun F
Background
Ablation of postinfarction ventricular tachycardia (VT) has been shown to reduce VT recurrence and decrease mortality. However, VT recurrence can occur despite extensive ablation procedures. The lack of inducibility of clinical VTs during ablation procedures remains problematic and may be in part responsible for VT recurrences. In this prospective study, we targeted documented but noninducible clinical VTs based on stored implantable cardioverter-defibrillator (ICD) electrograms.
Methods
Radiofrequency ablation was performed in a consecutive group of 66 postinfarction patients (mean age, 67.5±9.2 years; men, 61; mean left ventricular ejection fraction, 25.1±10.8%) in whom clinical VTs were not inducible during an ablation procedure. In the first 33 patients (control group), only inducible VTs were targeted, and in the second 33 patients, noninducible clinical VTs were also targeted by pace-mapping based on stored ICD-electrograms (ICD-electrogram-guided ablation group). Procedural and clinical outcomes were compared at 24 months post-ablation.
Results
VT recurred in 5 patients (15%) in whom the ICD-electrogram-guided approach was performed and in 13 patients (39%) in the control group. Freedom from recurrent VT was higher (log-rank P=0.04) in the ICD-electrogram-guided group, but there was no difference in ventricular fibrillation or in total mortality between both groups.
Conclusions
Ablation guided by pace-mapping of noninducible postinfarction clinical VTs based on ICD-electrograms is feasible and reduces the risk of recurrent VT.



Circ Arrhythm Electrophysiol: 29 Jun 2019; 12:e006978
Yokokawa M, Kim HM, Sharaf Dabbagh G, Siontis KC, ... Morady F, Bogun F
Circ Arrhythm Electrophysiol: 29 Jun 2019; 12:e006978 | PMID: 31216885
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Abstract

Secretoneurin Is an Endogenous Calcium/Calmodulin-Dependent Protein Kinase II Inhibitor That Attenuates Ca-Dependent Arrhythmia.

Ottesen AH, Carlson CR, Eken OS, Sadredini M, ... Røsjø H, Louch WE
Background
Circulating SN (secretoneurin) concentrations are increased in patients with myocardial dysfunction and predict poor outcome. Because SN inhibits CaMKIIδ (Ca/calmodulin-dependent protein kinase IIδ) activity, we hypothesized that upregulation of SN in patients protects against cardiomyocyte mechanisms of arrhythmia.
Methods
Circulating levels of SN and other biomarkers were assessed in patients with catecholaminergic polymorphic ventricular tachycardia (CPVT; n=8) and in resuscitated patients after ventricular arrhythmia-induced cardiac arrest (n=155). In vivo effects of SN were investigated in CPVT mice (RyR2 [ryanodine receptor 2]-R2474S) using adeno-associated virus-9-induced overexpression. Interactions between SN and CaMKIIδ were mapped using pull-down experiments, mutagenesis, ELISA, and structural homology modeling. Ex vivo actions were tested in Langendorff hearts and effects on Ca homeostasis examined by fluorescence (fluo-4) and patch-clamp recordings in isolated cardiomyocytes.
Results
SN levels were elevated in patients with CPVT and following ventricular arrhythmia-induced cardiac arrest. In contrast to NT-proBNP (N-terminal pro-B-type natriuretic peptide) and hs-TnT (high-sensitivity troponin T), circulating SN levels declined after resuscitation, as the risk of a new arrhythmia waned. Myocardial pro-SN expression was also increased in CPVT mice, and further adeno-associated virus-9-induced overexpression of SN attenuated arrhythmic induction during stress testing with isoproterenol. Mechanistic studies mapped SN binding to the substrate binding site in the catalytic region of CaMKIIδ. Accordingly, SN attenuated isoproterenol induced autophosphorylation of Thr287-CaMKIIδ in Langendorff hearts and inhibited CaMKIIδ-dependent RyR phosphorylation. In line with CaMKIIδ and RyR inhibition, SN treatment decreased Ca spark frequency and dimensions in cardiomyocytes during isoproterenol challenge, and reduced the incidence of Ca waves, delayed afterdepolarizations, and spontaneous action potentials. SN treatment also lowered the incidence of early afterdepolarizations during isoproterenol; an effect paralleled by reduced magnitude of L-type Ca current.
Conclusions
SN production is upregulated in conditions with cardiomyocyte Ca dysregulation and offers compensatory protection against cardiomyocyte mechanisms of arrhythmia, which may underlie its putative use as a biomarker in at-risk patients.



Circ Arrhythm Electrophysiol: 30 Mar 2019; 12:e007045
Ottesen AH, Carlson CR, Eken OS, Sadredini M, ... Røsjø H, Louch WE
Circ Arrhythm Electrophysiol: 30 Mar 2019; 12:e007045 | PMID: 30943765
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Abstract

When Sinus Tachycardia Becomes Too Much: Negative Effects of Excessive Upright Tachycardia on Cardiac Output in Vasovagal Syncope, Postural Tachycardia Syndrome, and Inappropriate Sinus Tachycardia.

Stewart JM, Medow MS, Visintainer P, Sutton R

- Upright posture reduces venous return, stroke volume and cardiac output (CO) while causing reflex sinus rate (HR) increase. Yet, in inappropriate sinus tachycardia (IST), postural tachycardia syndrome (POTS), and vasovagal syncope (VVS) symptomatic excessive HR occurs. We hypothesized CO reaches maximum as function of HR in all.- We recruited 12 healthy controls, 9 IST, 30 VVS and 30 POTS patients (13-23years) selected randomly by disorder not by HR, each fulfilled appropriate diagnostic criteria. Subjects were instrumented for electrocardiography, beat-to-beat blood pressure, respiratory rate, CO-Modelflow algorithm, and central blood volume (CBV) from impedance cardiography; 10min data was collected supine; subjects were tilted head-up for =/<10min. We computed phase differences, ΔΦ, between fluctuations of HR (ΔHR) and CO (ΔCO) tabulating data when phases were synchronized, determined by a squared nonlinear phase synchronization index (PhSI) >0.5, describing extent/validity of CO/HR coupling. We graphed results supine, 1min-post-tilt-up, mid-tilt, and pre-tilt-down using polar coordinates (HR - radius, ΔΦ - angle) plotting cos(ΔΦ) vs HR to determine if transition HR exists at which in-phase shifts to anti-phase above which CO decreases when HR further increases.- At baseline HR, diastolic and mean arterial pressure in IST and POTS were higher vs controls. Upright HR increased most in POTS then IST and VVS, with diverse changes in CO, SVR, and CBV. Each patient grouping was separately and collectively analyzed for HR change showing transition from in-phase to anti-phase (ΔΦ) as HR increased: HR =115±6(IST),123±8(POTS),124±7(VVS), p=ns. Controls never reached transitional HR.- Excessive HR independently and equivalently reduces upright CO, in IST, POTS and VVS.



Circ Arrhythm Electrophysiol: 14 Jan 2020; epub ahead of print
Stewart JM, Medow MS, Visintainer P, Sutton R
Circ Arrhythm Electrophysiol: 14 Jan 2020; epub ahead of print | PMID: 31941353
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Abstract

Three-Dimensional Printed Biopatches With Conductive Ink Facilitate Cardiac Conduction When Applied to Disrupted Myocardium.

Pedrotty DM, Kuzmenko V, Karabulut E, Sugrue AM, ... Gatenholm P, Kapa S
Background
Reentrant ventricular arrhythmias are a major cause of sudden death in patients with structural heart disease. Current treatments focus on electrically homogenizing regions of scar contributing to ventricular arrhythmia with ablation or altering conductive properties using antiarrhythmic drugs. The high conductivity of carbon nanotubes may allow restoration of conduction in regions where impaired electrical conduction results in functional abnormalities. We propose a new concept for arrhythmia treatment using a stretchable, flexible biopatch with conductive properties to attempt to restore conduction across regions in which activation is disrupted.
Methods
Carbon nanotube patches composed of nanofibrillated cellulose/single-walled carbon nanotube ink 3-dimensionally printed in conductive patterns onto bacterial nanocellulose were developed and evaluated for conductivity, flexibility, and mechanical properties. The patches were applied on 6 canines to epicardium before and after surgical disruption. Electroanatomic mapping was performed on normal epicardium, then repeated over surgically disrupted epicardium, and then finally with the patch applied passively.
Results
We developed a 3-dimensional printable carbon nanotube ink complexed on bacterial nanocellulose that was (1) expressable through 3-dimensional printer nozzles, (2) electrically conductive, (3) flexible, and (4) stretchable. Six canines underwent thoracotomy, and, during epicardial ventricular pacing, mapping was performed. We demonstrated disruption of conduction after surgical incision in all 6 canines based on activation mapping. The patch resulted in restored conduction based on mapping and assessment of conduction direction and velocities in all canines.
Conclusions
We have demonstrated 3-dimensional custom-printed electrically conductive carbon nanotube patches can be surgically manipulated to improve cardiac conduction when passively applied to surgically disrupted epicardial myocardium in canines.



Circ Arrhythm Electrophysiol: 27 Feb 2019; 12:e006920
Pedrotty DM, Kuzmenko V, Karabulut E, Sugrue AM, ... Gatenholm P, Kapa S
Circ Arrhythm Electrophysiol: 27 Feb 2019; 12:e006920 | PMID: 30845835
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Abstract

New Model of Automated Patient-Reported Outcomes Applied in Atrial Fibrillation.

Hussein AA, Lindsay B, Madden R, Martin D, ... Nissen SE, Wazni OM

Background The value of patient-reported outcomes (PRO) is increasingly recognized in patient-centered care. Longitudinal data collection may be challenging and cost prohibitive. Automation of PRO collection may complement routine clinical follow-up, especially for procedures aiming to improve quality of life, such as atrial fibrillation (AF) ablation. Methods We aimed to develop a fully automated platform to collect PRO and evaluate its first clinical application in a prospective cohort of AF ablation. The duration of follow-up and data availability were assessed with automated PRO and routine follow-up versus routine follow-up alone (primary outcome). Quality of life and healthcare utilization (secondary outcomes) by PRO were assessed. Results Between 2013 and 2016, 2175 patients were eligible to receive 10 903 PRO assessment invitations, and the automated platform sent all invitations as programmed. More follow-up assessments were obtained with automated PRO and routine follow-up compared with routine follow-up alone (12 859 versus 10 248; P<0.0001) which allowed longer duration of follow-up (378 versus 217 days, 74% increase; P<0.0001). By automated PRO, a large number of disease-specific variables were collected and showed improvement in quality of life (baseline median AF symptom severity score AFSSS of 12 [6-18] and ranged between 2 and 3 on subsequent assessments; P<0.0001). This improvement was also true for each of the AFSSS individual components ( P<0.0001). In PRO, there was a significant reduction in AF burden (such as frequency and duration of episodes; P<0.0001) and associated healthcare utilization (including emergency visits and hospitalizations; P<0.0001) after the ablation procedures. Conclusions A fully automated system for PRO collection enhanced clinical follow-up and allowed collection of disease-specific data when applied in a prospective cohort of AF ablation.



Circ Arrhythm Electrophysiol: 27 Feb 2019; 12:e006986
Hussein AA, Lindsay B, Madden R, Martin D, ... Nissen SE, Wazni OM
Circ Arrhythm Electrophysiol: 27 Feb 2019; 12:e006986 | PMID: 30866665
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Abstract

Pulsed Field Ablation vs Radiofrequency Ablation: Esophageal Injury in a Novel Model.

Koruth JS, Kuroki K, Kawamura I, Brose R, ... Dukkipati SR, Reddy VY

- Pulsed field ablation (PFA) can be myocardium-selective, potentially sparing the esophagus during left atrial ablation. In an in vivo porcine esophageal injury model, we compared the effects of newer biphasic PFA with radiofrequency ablation (RFA).- In 10 animals, under general anesthesia, the lower esophagus was deflected towards the inferior vena cava (IVC) using an esophageal deviation balloon, and ablation was performed from within the IVC at areas of esophageal contact. Four discrete esophageal sites were targeted in each animal: 6 animals received 8 PFA applications/site (2 kV, multispline catheter), and 4 animals received 6 clusters of irrigated RFA applications (30W x 30 seconds, 3.5mm catheter). All animals were survived to 25 days, sacrificed and the esophagus submitted for pathological examination, including 10 discrete histological sections/esophagus.- The animals weight increased by 13.7±6.2 and 6.8±6.3 % (p=0.343) in the PFA and RFA cohorts, respectively. No PFA animals (0 of 6, 0%) developed abnormal in-life observations, but 1 of 4 RFA animals (25%) developed fever and dyspnea. On necropsy, no PFA animals (0 of 6, 0%) demonstrated esophageal lesions. In contrast, esophageal injury occurred in all RFA animals (4 of 4, 100%; p=0.005): a mean of 1.5 mucosal lesions/animal (length - 21.8±8.9 mm, width - 4.9±1.4 mm) were observed, including one esophago-pulmonary fistula, and deep esophageal ulcers in the other animals. Histological examination demonstrated tissue necrosis surrounded by acute and chronic inflammation and fibrosis. The necrotic RFA lesions involved multiple esophageal tissue layers with evidence of arteriolar medial thickening and fibrosis of peri-esophageal nerves. Abscess formation and full-thickness esophageal wall disruptions were seen in areas of perforation/fistula.- In this novel porcine model of esophageal injury, biphasic PFA induced no chronic histopathological esophageal changes, while RFA demonstrated a spectrum of esophageal lesions including fistula and deep esophageal ulcers and abscesses.



Circ Arrhythm Electrophysiol: 23 Jan 2020; epub ahead of print
Koruth JS, Kuroki K, Kawamura I, Brose R, ... Dukkipati SR, Reddy VY
Circ Arrhythm Electrophysiol: 23 Jan 2020; epub ahead of print | PMID: 31977250
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Abstract

Novel Irrigated Temperature-Controlled Lattice Ablation Catheter for Ventricular Ablation: A Preclinical Multimodality Biophysical Characterization.

Shapira-Daniels A, Barkagan M, Yavin H, Sroubek J, ... Neuzil P, Anter E
Background
Ventricular tachycardia ablation is often limited by insufficient lesion creation. A novel radiofrequency catheter with an expandable lattice electrode has a larger surface area capable of delivering higher currents at a lower density to potentially increase lesion dimensions without overheating.
Methods
This 8F bidirectional irrigated catheter (Sphere-9, Affera Inc) has a 9 mm spherical lattice tip (\"lattice\") with an effective surface area 10-fold larger than standard linear catheters. Nine surface thermocouples provide temperature feedback to a proprietary high-current generator operating in a temperature-controlled mode. Ex vivo phase: in 11 bovine hearts, unipolar ablation at 30, 60, and 120 seconds was compared between the lattice (Tmax60°C) and a standard linear irrigated-tip catheter (40 W) at contact force of 10 g. In 5 porcine hearts, bipolar ablation was compared between the catheters (Tmax60°C versus 40 W; 60 seconds). In vivo phase: in 9 swine, ventricular ablation at Tmax60°C versus 40 W was performed for 60 seconds. In addition, direct tissue temperature at 3- and 7-mm tissue depth was measured in a thigh muscle preparation.
Results
Ex vivo: lattice produced deeper lesions at 30, 60, and 120 seconds application duration (6.7±1.3 versus 4.8±1.2 mm; 8.3±1.4 versus 5.4±0.8 mm; 10.0±1.6 versus 6.1±1.6 mm, respectively, ≤0.001 for all). Bipolar lesions were deeper (15.8±4.1 versus 10.5±1.4 mm, <0.001) and more likely to be transmural (80% versus 0%, =0.002). In vivo: lattice produced deeper lesions (10.5±1.4 versus 6.5±0.8 mm, ≤0.001). Tissue temperature at 7 mm was higher with the lattice (+15.1±2.4°C; <0.001). The steam-pop occurrence was lower with the lattice (total: 4% versus 18%, =0.02; in vivo 0% versus 14.2%, =0.13).
Conclusions
This novel radiofrequency system produces larger ventricular lesions compared with standard irrigated catheters and at a lower risk of tissue overheating. This may improve the efficacy of ventricular tachycardia ablation procedures while reducing the number of applications and procedural duration.



Circ Arrhythm Electrophysiol: 30 Oct 2019; 12:e007661
Shapira-Daniels A, Barkagan M, Yavin H, Sroubek J, ... Neuzil P, Anter E
Circ Arrhythm Electrophysiol: 30 Oct 2019; 12:e007661 | PMID: 31707809
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