Journal: Circ Arrhythm Electrophysiol

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Abstract

Machine Learning-derived Fractal Features of Shape and Texture of the Left Atrium and Pulmonary Veins from Cardiac CT Scans are Associated with Risk of Recurrence of Atrial Fibrillation Post-ablation.

Firouznia M, Feeny AK, LaBarbera MA, McHale M, ... Chung MK, Madabhushi A

Background:
- We hypothesized that computerized morphologic analysis of the LA and pulmonary veins (PVs) via fractal measurements of shape and texture features of the LA myocardial wall could predict AF recurrence after ablation. Methods - Pre-ablation contrast CT scans were collected for 203 patients who underwent AF ablation. The LA body, PVs, and myocardial wall were segmented using a semi-automated region growing method. Twenty-eight fractal-based shape and texture-based features were extracted from resulting segments. The top features most associated with post-ablation recurrence were identified using feature selection and subsequently evaluated with a Random Forest classifier. Feature selection and classifier construction were performed on a discovery cohort (D1) of 137 patients; classifiers were subsequently validated on an independent set (D2) of 66 patients. Dedicated classifiers to capture the fractal and morphologic properties of LA body (CLA), PVs (CPV), and LA myocardial (CLAM) tissue were constructed, as well as a model (CAll) capturing properties of all segmented compartments. Fractal-based models were also compared against a model employing machine estimation of LA volume. To assess the effect of clinical parameters, such as AF type and catheter technique, a clinical model (Cclin) was also compared against CAll. Results - Statistically significant differences were observed for fractal features of CLA, CLAM and CAll in distinguishing AF recurrence (p<0.001) on D1. Using the five top features, CAll had the best prediction performance (AUC=0.81 [95% Confidence Interval (CI): 0.78-0.85]), followed by CPV (AUC=0.78 [95% CI: 0.74-0.80]) and CLA (AUC=0.70 [95% CI: 0.63-0.78]) on D2. The clinical parameter model Cclin yielded an AUC=0.70 [95% CI: 0.65-0.77], while the atrial volume model yielded an AUC=0.59. Combining CAll and Cclin on D2 improved the AUC to 0.87 [95% CI: 0.82-0.93].
Conclusions:
- Fractal measurements of the LA, PVs, and atrial myocardium on CT scans were associated with likelihood of post-ablation AF recurrence.




Circ Arrhythm Electrophysiol: 11 Feb 2021; epub ahead of print
Firouznia M, Feeny AK, LaBarbera MA, McHale M, ... Chung MK, Madabhushi A
Circ Arrhythm Electrophysiol: 11 Feb 2021; epub ahead of print | PMID: 33576688
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Abstract

Pivotal Study of a Novel Motor Driven Endoscopic Ablation System.

Schmidt B, Petru J, Chun JKR, Sediva L, ... Chen S, Neuzil P

Background:
- The HeartLight™ endoscopic ablation system (HL-EAS), has proven similar efficacy as radiofrequency guided pulmonary vein isolation (PVI) in prospective randomized studies though longer procedure times were reported. Recently, the option of a new ablation mode (RAPID™) was added, during which the laser arc generator is swept around the PV antrum by an integrated motor drive at a pre-defined speed for continuous ablation. We sought to determine the performance of the new EAS (X3). Methods - The study was prospective, two center, and historically controlled (comparison to pivotal HL study). The primary endpoint was ablation time (time from insertion of the X3 catheter to the end of the last 30-minute wait period). Transtelephonic monitoring was performed from 90 days to 12 months after ablation. Results - A total of 60 patients were enrolled at two centers. Except one all PVs were treated with RAPID mode. Acute PVI was achieved in 225/228 of these PVs (98.7%). The ablation time, was significantly shorter with X3 than in the HL study (77.3 ± 25.8 min versus 173.8 ± 46.6 min; p<0.0001). Procedure time and fluoroscopy time were also significantly shorter (103.7 ± 32.3 min versus 236.0 ± 52.8min; p<0.0001; 6.9 ± 3.5 versus 35.6 ± 18.2; p<0.0001). PVI after the first circular lesion was achieved in 91.6% of PVs (206/225). Two strokes and one late pericardial effusion were noted in the treatment group that were not deemed device related. The 6-month and 12-month AF-Free rates for X3 compare favorably with the rates reported for HL, 89.5% versus 75.0% and 71.9% versus 61.1%, respectively.
Conclusions:
- The novel X3 generation EAS allows for rapid PVI by continuous lesion deployment. This was associated with a significant reduction in ablation and procedure times while maintaining the safety and chronic effectiveness in comparison to historical controls.




Circ Arrhythm Electrophysiol: 10 Feb 2021; epub ahead of print
Schmidt B, Petru J, Chun JKR, Sediva L, ... Chen S, Neuzil P
Circ Arrhythm Electrophysiol: 10 Feb 2021; epub ahead of print | PMID: 33570423
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Abstract

Worldwide Survey of COVID-19 Associated Arrhythmias.

Coromilas EJ, Kochav S, Goldenthal I, Biviano A, ... Fernández-Vázquez F, Wan EY

Background:
- COVID-19 has led to over 1 million deaths worldwide and has been associated with cardiac complications including cardiac arrhythmias. The incidence and pathophysiology of these manifestations remain elusive. In this worldwide survey of patients hospitalized with COVID-19 who developed cardiac arrhythmias, we describe clinical characteristics associated with various arrhythmias, as well as global differences in modulations of routine electrophysiology practice during the pandemic. Methods - We conducted a retrospective analysis of patients hospitalized with COVID-19 infection worldwide with and without incident cardiac arrhythmias. Patients with documented atrial fibrillation (AF), atrial flutter (AFL), supraventricular tachycardia (SVT), non-sustained or sustained ventricular tachycardia (VT), ventricular fibrillation (VF), atrioventricular block (AVB), or marked sinus bradycardia (HR<40bpm) were classified as having arrhythmia. De-identified data was provided by each institution and analyzed. Results - Data was collected for 4,526 patients across 4 continents and 12 countries, 827 of whom had an arrhythmia. Cardiac comorbidities were common in patients with arrhythmia: 69% had hypertension, 42% diabetes mellitus, 30% had heart failure and 24% coronary artery disease. Most had no prior history of arrhythmia. Of those who did develop an arrhythmia, the majority (81.8%) developed atrial arrhythmias, 20.7% developed ventricular arrhythmias, and 22.6% had bradyarrhythmia. Regional differences suggested a lower incidence of AF in Asia compared to other continents (34% vs. 63%). Most patients in in North America and Europe received hydroxychloroquine, though the frequency of hydroxychloroquine therapy was constant across arrhythmia types. Forty-three percent of patients who developed arrhythmia were mechanically ventilated and 51% survived to hospital discharge. Many institutions reported drastic decreases in electrophysiology procedures performed.
Conclusions:
- Cardiac arrhythmias are common and associated with high morbidity and mortality among patients hospitalized with COVID-19 infection. There were significant regional variations in the types of arrhythmias and treatment approaches.




Circ Arrhythm Electrophysiol: 06 Feb 2021; epub ahead of print
Coromilas EJ, Kochav S, Goldenthal I, Biviano A, ... Fernández-Vázquez F, Wan EY
Circ Arrhythm Electrophysiol: 06 Feb 2021; epub ahead of print | PMID: 33554620
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Abstract

Metformin Is Associated with a Lower Risk of Atrial Fibrillation and Ventricular Arrhythmias Compared to Sulfonylureas: An Observational Study.

Ostropolets A, Elias PA, Reyes MV, Wan EY, ... Hripcsak G, Morrow JP

Background:
- Type 2 diabetes (DM2) is one of the most common chronic disorders worldwide and is an important cause of cardiovascular disease. Studies investigating the risk of atrial and ventricular arrhythmias in diabetic patients taking different oral diabetes medications are sparse. Methods - We used IBM MarketScan® Medicare Supplemental Database to examine the risk of arrhythmias for patients on different oral diabetes medications by propensity score matching. Results - We found that patients on metformin monotherapy had significantly reduced risk of atrial arrhythmias, including atrial fibrillation, compared to monotherapy with DPP4 or TZD medications. Patients on metformin monotherapy had significantly reduced risk of atrial arrhythmias, ventricular arrhythmias, and bradycardia compared to monotherapy with sulfonylureas. Combination therapy with sulfonylureas and metformin had an increased risk of atrial arrhythmias compared to some other combinations.
Conclusions:
- Different oral diabetes medications have significantly different long-term risk of arrhythmia. Specifically, metformin is associated with reduced risk of atrial fibrillation and ventricular arrhythmias compared to sulfonylureas.




Circ Arrhythm Electrophysiol: 06 Feb 2021; epub ahead of print
Ostropolets A, Elias PA, Reyes MV, Wan EY, ... Hripcsak G, Morrow JP
Circ Arrhythm Electrophysiol: 06 Feb 2021; epub ahead of print | PMID: 33554609
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Abstract

Familial Evaluation in Idiopathic Ventricular Fibrillation: Diagnostic Yield and Significance of J-Wave Syndromes.

Mellor GJ, Blom LJ, Groeneveld SA, Winkel BG, ... Hassink RJ, Behr ER

Background:
- Familial cascade screening is well established in patients with heritable cardiac disease and in cases of Sudden Arrhythmic Death Syndrome (SADS). The clinical benefit of family screening in idiopathic ventricular fibrillation (IVF) is unknown. Methods - Patients with IVF were identified from national and institutional registries. All underwent systematic and comprehensive clinical evaluation to exclude identifiable causes of cardiac arrest with a minimum requirement of ECG, cardiac (echocardiogram and/or MRI) and coronary imaging, exercise ECG and sodium channel blocker (SCB) provocation. Additional investigations including genetic testing were performed at the physician\'s discretion. First-degree relatives who were assessed with at least a 12-lead ECG were included in the final cohort. Results of additional investigations, performed at the physician\'s discretion, were also recorded. Results were coded as normal, abnormal or minor findings. Results - We identified 201 first-degree relatives of 96 IVF patients. In addition to a 12 lead ECG, echocardiography was performed in 159 (79%) and ≥ 1 additional investigation in 162 (80%) relatives. An inherited arrhythmia syndrome was diagnosed in 5 (3%) individuals from 4 (4%) families. Two relatives hosted the DPP6 risk haplotype identified in a single proband, one of whom received a primary prevention ICD. In three separate families an asymptomatic parent of the IVF proband developed a type 1 Brugada ECG pattern during SCB provocation. All were managed with lifestyle measures only. The Early Repolarisation ECG pattern (ER) was present in 16% probands and was more common in relatives in those families than those where the proband did not have ER (25% vs. 8%, p=0.04).
Conclusions:
- The yield of family screening in relatives of IVF probands is low when the proband is comprehensively investigated. The significance of J wave syndromes in relatives and the role for systematic SCB provocation are, however, uncertain and require further research.




Circ Arrhythm Electrophysiol: 06 Feb 2021; epub ahead of print
Mellor GJ, Blom LJ, Groeneveld SA, Winkel BG, ... Hassink RJ, Behr ER
Circ Arrhythm Electrophysiol: 06 Feb 2021; epub ahead of print | PMID: 33550818
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Abstract

Electrical Substrate Ablation for Refractory Ventricular Fibrillation: Results of the AVATAR Study.

Krummen DE, Ho G, Hoffmayer KS, Schweis F, ... Rappel WJ, Narayan SM

Background:
- Refractory ventricular fibrillation (VF) is a challenging clinical entity, for which ablation of triggering premature ventricular complexes (PVCs) is described. When PVCs are infrequent and multifocal, the optimal treatment strategy is uncertain. Methods - We prospectively enrolled consecutive patients presenting with multiple ICD shocks for VF refractory to antiarrhythmic drug therapy, exhibiting infrequent (≤3%), multifocal PVCs (≥3 morphologies). Procedurally, VF was induced with rapid pacing and mapped, identifying sites of conduction slowing and rotation or rapid focal activation. VF electrical substrate ablation (VESA) was then performed. Outcomes were compared against reference patients with VF who were unable or unwilling to undergo catheter ablation. The primary outcome was a composite of ICD shock, electrical storm, or all-cause mortality. Results - VF was induced and mapped in 6 patients (60±10 y, LVEF 46±19%) with ischemic (n=3) and nonischemic cardiomyopathy. An average of 3.3±0.5 sites of localized reentry during VF were targeted for radiofrequency ablation (38.3±10.9 minutes) during sinus rhythm, rendering VF non-inducible with pacing. Freedom from the primary outcome was 83% in the VF ablation group versus 17% in 6 non-ablation reference patients at a median of 1.0 years (IQR 0.5-1.5 years, p=0.046) follow-up.
Conclusions:
- VESA is associated with a reduction in the combined endpoint compared with the non-ablation reference group. Additional work is required to understand the precise pathophysiologic changes which promote VF in order to improve preventative and therapeutic strategies.




Circ Arrhythm Electrophysiol: 06 Feb 2021; epub ahead of print
Krummen DE, Ho G, Hoffmayer KS, Schweis F, ... Rappel WJ, Narayan SM
Circ Arrhythm Electrophysiol: 06 Feb 2021; epub ahead of print | PMID: 33550811
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Abstract

Ongoing Risk of Ventricular Arrhythmias and All-cause Mortality at Implantable Cardioverter Defibrillator Generator Change: A Systematic Review and Meta-analysis.

Yuyun MF, Erqou SA, Peralta AO, Hoffmeister PS, ... Joseph J, Singh JP

Background:
- Uncertainty still surrounds implantable cardioverter defibrillator (ICD) generator change at time of elective replacement indicator (ERI), in primary prevention patients with improved left ventricular ejection fraction (LVEF) beyond guideline recommendations or without prior appropriate ICD therapies. Methods - We conducted a meta-analysis of studies assessing the risk of appropriate ICD therapies and all-cause mortality after generator change in patients with improved LVEF > 35% versus unimproved LVEF ≤ 35% or patients without versus with prior appropriate ICD therapies during the life of their first ICD generator. A systematic electronic search of PubMed, EMBASE, and Cochrane Library databases until December 31st, 2019 was performed. Estimates were combined using random-effects model meta-analyses. Results - In 15 studies that included 29730 patients, 25.3% had LVEF improvement >35% at time of generator change. The pooled annual incidence of appropriate ICD therapies was significantly lower in those with improved LVEF, compared to patients with unimproved LVEF: 4.6% versus 10.7%; risk ratio (RR) 0.50 (95% CI 0.36-0.68), p <0.0001. The pooled rate of all-cause mortality was 6.6% versus 10.9% per year, RR of 0.65 (95% CI 0.62-0.69), p < 0.0001. Risk of inappropriate shock was comparable between the two groups (p = 0.750). In 8 studies (N = 27209), the pooled incidence of ventricular arrhythmia (VA) was significantly lower in patients without prior ICD therapies (3.9% per annum), compared to those with prior ICD therapies (12.5 % per annum), RR of 0.37 (95% CI 0.33-0.41), P<0.001.
Conclusions:
- There was significant reduction in risk of ventricular arrhythmias and mortality in patients with improved versus unimproved LVEF or those who received versus those who did not receive appropriate ICD therapies during the life of their first ICD generator. However, we found a substantial residual outcome risk in these groups of patients.




Circ Arrhythm Electrophysiol: 05 Feb 2021; epub ahead of print
Yuyun MF, Erqou SA, Peralta AO, Hoffmeister PS, ... Joseph J, Singh JP
Circ Arrhythm Electrophysiol: 05 Feb 2021; epub ahead of print | PMID: 33554611
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Abstract

Outcomes of Pediatric Patients With Defibrillators Following Initial Presentation With Sudden Cardiac Arrest.

Robinson JA, LaPage MJ, Atallah J, Webster G, ... Spar DS, Czosek RJ
Background
Implantable cardioverter defibrillators (ICD) are recommended for secondary prevention after sudden cardiac arrest (SCA). The outcomes of pediatric patients receiving an ICD after SCA remain unclear. The objective of this study is to evaluate outcomes, future risk for appropriate shocks, and identify characteristics associated with appropriate ICD therapy during follow-up.
Methods
Multicenter retrospective analysis of patients (age ≤21 years) without prior cardiac disease who received an ICD following SCA. Patient/device characteristics, cardiac function, and underlying diagnoses were collected, along with SCA event characteristics. Patient outcomes including complications and device therapies were analyzed.
Results
In total, 106 patients were included, median age 14.7 years. Twenty (19%) received appropriate shocks and 16 (15%) received inappropriate shocks (median follow-up 3 years). First-degree relative with SCA was associated with appropriate shocks (P<0.05). In total, 40% patients were considered idiopathic. Channelopathy was the most frequent late diagnosis not made at time of presentation. Neither underlying diagnosis nor idiopathic status was associated with increased incidence of appropriate shock. Monomorphic ventricular tachycardia (hazard ratio, 4.6 [1.2-17.3]) and family history of sudden death (hazard ratio, 6.5 [1.4-29.8]) were associated with freedom from appropriate shock in a multivariable model (area under the receiver operating characteristic curve, 0.8). Time from diagnoses to evaluation demonstrated a nonlinear association with freedom from appropriate shock (P=0.015). In patients >2 years from implantation, younger age (P=0.02) and positive exercise test (P=0.04) were associated with appropriate shock.
Conclusions
The risk of future device therapy is high in pediatric patients receiving an ICD after SCA, irrelevant of underlying disease. Lack of a definitive diagnosis after SCA was not associated with lower risk of subsequent events and does not obviate the need for secondary prophylaxis.



Circ Arrhythm Electrophysiol: 30 Jan 2021; 14:e008517
Robinson JA, LaPage MJ, Atallah J, Webster G, ... Spar DS, Czosek RJ
Circ Arrhythm Electrophysiol: 30 Jan 2021; 14:e008517 | PMID: 33401923
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Abstract

Discovering and Visualizing Disease-Specific Electrocardiogram Features Using Deep Learning: Proof-of-Concept in Phospholamban Gene Mutation Carriers.

van de Leur RR, Taha K, Bos MN, van der Heijden JF, ... Asselbergs FW, van Es R
Background
ECG interpretation requires expertise and is mostly based on physician recognition of specific patterns, which may be challenging in rare cardiac diseases. Deep neural networks (DNNs) can discover complex features in ECGs and may facilitate the detection of novel features which possibly play a pathophysiological role in relatively unknown diseases. Using a cohort of PLN (phospholamban) p.Arg14del mutation carriers, we aimed to investigate whether a novel DNN-based approach can identify established ECG features, but moreover, we aimed to expand our knowledge on novel ECG features in these patients.
Methods
A DNN was developed on 12-lead median beat ECGs of 69 patients and 1380 matched controls and independently evaluated on 17 patients and 340 controls. Differentiating features were visualized using Guided Gradient Class Activation Mapping++. Novel ECG features were tested for their diagnostic value by adding them to a logistic regression model including established ECG features.
Results
The DNN showed excellent discriminatory performance with a c-statistic of 0.95 (95% CI, 0.91-0.99) and sensitivity and specificity of 0.82 and 0.93, respectively. Visualizations revealed established ECG features (low QRS voltages and T-wave inversions), specified these features (eg, R- and T-wave attenuation in V2/V3) and identified novel PLN-specific ECG features (eg, increased PR-duration). The logistic regression baseline model improved significantly when augmented with the identified features (P<0.001).
Conclusions
A DNN-based feature detection approach was able to discover and visualize disease-specific ECG features in PLN mutation carriers and revealed yet unidentified features. This novel approach may help advance diagnostic capabilities in daily practice.



Circ Arrhythm Electrophysiol: 30 Jan 2021; 14:e009056
van de Leur RR, Taha K, Bos MN, van der Heijden JF, ... Asselbergs FW, van Es R
Circ Arrhythm Electrophysiol: 30 Jan 2021; 14:e009056 | PMID: 33401921
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Abstract

Cryoballoon Versus Laserballoon: Insights From the First Prospective Randomized Balloon Trial in Catheter Ablation of Atrial Fibrillation.

Chun JKR, Bordignon S, Last J, Mayer L, ... Chen S, Schmidt B
Background
Pulmonary vein isolation (PVI) represents the cornerstone in atrial fibrillation ablation. Cryoballoon and laserballoon catheters have emerged as promising devices but lack randomized comparisons. Therefore, we sought to compare efficacy and safety comparing both balloons in patients with persistent and paroxysmal atrial fibrillation (AF).
Methods
Symptomatic AF patients (n=200) were prospectively randomized (1:1) to receive either cryoballoon or laserballoon PVI (cryoballoon: n=100: 50 paroxysmal atrial fibrillation + 50 persistent AF versus laserballoon: n=100: 50 paroxysmal atrial fibrillation + 50 persistent AF). All antiarrhythmic drugs were stopped after ablation. Follow-up included 3-day Holter-ECG recordings and office visits at 3, 6, and 12 months. Primary efficacy end point was defined as freedom from atrial tachyarrhythmia between 90 and 365 days after a single ablation. Secondary end points included procedural parameters and periprocedural complications.
Results
Patient baseline parameters were not different between both groups. In all (n=200) complete PVI was obtained and the entire follow-up accomplished. Balloon only PVI was obtained in 98% (cryoballoon) versus 95% (laserballoon) requiring focal touch-up in 2 and 5 patients, respectively. Procedure but not fluoroscopy time was significantly shorter in the cryoballoon group (50.9±21.0 versus 96.0±20.4 minutes; P<0.0001 and 7.4±4.4 versus 8.4±3.2 minutes, P=0.083). Overall, the primary end point of no atrial tachyarrhythmia recurrence was met in 79% (cryoballoon: 80.0% versus laserballoon: 78.0%, P=ns). No death, atrio-esophageal fistula, tamponade, or vascular laceration requiring surgery occurred. In the cryoballoon group, 8 transient but no persistent phrenic nerve palsy were noted compared with 2 persistent phrenic nerve palsy and one transient ischemic attack in the laserballoon group.
Conclusions
Both balloon technologies represent highly effective and safe tools for PVI resulting in similar favorable rhythm outcome after 12 months. Use of the cryoballoon is associated with significantly shorter procedure but not fluoroscopy time.



Circ Arrhythm Electrophysiol: 30 Jan 2021; 14:e009294
Chun JKR, Bordignon S, Last J, Mayer L, ... Chen S, Schmidt B
Circ Arrhythm Electrophysiol: 30 Jan 2021; 14:e009294 | PMID: 33417476
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Abstract

Circular Multielectrode Pulsed Field Ablation Catheter Lasso Pulsed Field Ablation: Lesion Characteristics, Durability, and Effect on Neighboring Structures.

Yavin H, Brem E, Zilberman I, Shapira-Daniels A, ... Wazni O, Anter E
Background
Pulsed field ablation (PFA) is a nonthermal energy with potential safety advantages over radiofrequency ablation. This study investigated a novel PFA system-a circular multielectrode catheter (PFA lasso) and a multichannel generator designed to work with Carto 3 mapping system.
Methods
A 7.5F bidirectional circular catheter with 10 electrodes and variable expansion was designed for PFA (biphasic, 1800 Volts). This study included a total of 16 swine used to investigate the following 3 experimental aims: Aim 1 examined the feasibility to create a right atrial ablation line of block from the superior vena cava to the inferior vena cava. Aim 2 examined the effect of PFA on lesion maturation including durability after a 30-day survival period. Aim 3 examined the effect of high-intensity PFA (10 applications) on esophageal and phrenic nerve tissue in comparison to normal intensity radiofrequency ablation (1-2 applications). Histopathologic analysis of all cardiac, esophageal, and phrenic nerve tissue was performed.
Results
Acute line of block was achieved in 12/12 swine (100%) and required a total PFA time of 14 seconds (interquartile range [IQR], 9-24.5) per line. Ablation line durability after 28±3 days was maintained in 11/12 (91.7%) swine. PFA resulted in transmural lesions in 179/183 (97.8%) sections and a median lesion width of 14.2 mm. High-intensity PFA (9 [IQR, 8-14] application) had no effect on the esophagus while standard intensity radiofrequency ablation (1.5 [IQR, 1-2] applications) resulted in deep esophageal tissue injury involving the muscularis propria and adventitia layers. High-intensity PFA (16 [IQR, 10-28] applications) has no effect on phrenic nerve function and structure while standard dose radiofrequency ablation (1.5 [IQR, 1-2] applications) resulted in acute phrenic nerve paralysis.
Conclusions
In this preclinical model, a multielectrode circular catheter and multichannel generator produced durable atrial lesions with lower vulnerability to esophageal or phrenic nerve damage.



Circ Arrhythm Electrophysiol: 30 Jan 2021; 14:e009229
Yavin H, Brem E, Zilberman I, Shapira-Daniels A, ... Wazni O, Anter E
Circ Arrhythm Electrophysiol: 30 Jan 2021; 14:e009229 | PMID: 33417475
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Abstract

Periaortic Ventricular Tachycardias in Nonischemic Cardiomyopathy: Substrate and Electrocardiographic Correlations.

Nakajima I, Narui R, Aboud AA, Adeola O, ... Michaud GF, Stevenson WG
Background
Periaortic fibrotic ventricular tachycardia (VT) substrate is common in nonischemic cardiomyopathy (NICM), often intramural, and difficult to ablate. We sought to better characterize normal and abnormal periaortic voltage map parameters and NICM periaortic VTs.
Methods
In 15 patients without heart disease, the 5th percentile of endocardial voltage for increasing distance from the aortic valve ring was determined. In 53 consecutive patients with NICM (64±11 years; left ventricular ejection fraction 31±10%) undergoing ablation of recurrent VT, periaortic electrogram voltage and VT characteristics were analyzed.
Results
In healthy patients, the fifth percentile of the bipolar voltage increased proportional to the distance from the aortic valve ring, from 1.0 mV at 1 cm to 1.5 mV at 1.5 cm; the corresponding unipolar voltage cutoffs were 5.0 and 7.5 mV. A total of 160 VTs were induced in 53 patients with NICM, of which 28 VTs in 20 patients had periaortic origins. Periaortic VTs were associated with similar periaortic bipolar voltage, but lower UVs consistent with intramural fibrosis as an important substrate. Periaortic VTs could be divided into left and right bundle branch block forms with mapping showing right septal and lateral exits. Left bundle branch block VTs were more often acutely abolished with ablation (100% versus 69%; P=0.034), but with a 23% incidence of heart block. Greater extent of low voltage was associated with more induced VTs and worse acute outcome.
Conclusions
Adjusting voltage parameters based on distance from the aortic valve may improve definition of left ventricular outflow tract arrhythmia substrate. Periaortic VTs are common in NICM, often associated with intramural substrate and can be divided into left bundle branch block and right bundle branch block types associated with different ablation outcomes and risks.



Circ Arrhythm Electrophysiol: 30 Jan 2021; 14:e008887
Nakajima I, Narui R, Aboud AA, Adeola O, ... Michaud GF, Stevenson WG
Circ Arrhythm Electrophysiol: 30 Jan 2021; 14:e008887 | PMID: 33417473
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Abstract

Activation of TRPC (Transient Receptor Potential Canonical) Channel Currents in Iron Overloaded Cardiac Myocytes.

Siri-Angkul N, Song Z, Fefelova N, Gwathmey JK, ... Chattipakorn N, Xie LH
Background
Arrhythmias and heart failure are common cardiac complications leading to substantial morbidity and mortality in patients with hemochromatosis, yet mechanistic insights remain incomplete. We investigated the effects of iron (Fe) on electrophysiological properties and intracellular Ca2+ (Ca2+i) handling in mouse left ventricular cardiomyocytes.
Methods
Cardiomyocytes were isolated from the left ventricle of mouse hearts and were superfused with Fe3+/8-hydroxyquinoline complex (5-100 μM). Membrane potential and ionic currents including TRPC (transient receptor potential canonical) were recorded using the patch-clamp technique. Ca2+i was evaluated by using Fluo-4. Cell contraction was measured with a video-based edge detection system. The role of TRPCs in the genesis of arrhythmias was also investigated by using a mathematical model of a mouse ventricular myocyte with the incorporation of the TRPC component.
Results
We observed prolongation of the action potential duration and induction of early and delayed afterdepolarizations in myocytes superfused with 15 µmol/L Fe3+/8-hydroxyquinoline complex. Iron treatment decreased the peak amplitude of the L-type Ca2+ current and total K+ current, altered Ca2+i dynamics, and decreased cell contractility. During the final phase of Fe treatment, sustained Ca2+i waves and repolarization failure occurred and ventricular cells became unexcitable. Gadolinium abolished Ca2+i waves and restored the resting membrane potential to the normal range. The involvement of TRPC activation was confirmed by TRPC channel current recordings in the absence or presence of functional TRPC channel antibodies. Computer modeling captured the same action potential and Ca2+i dynamics and provided additional mechanistic insights.
Conclusions
We conclude that iron overload induces cardiac dysfunction that is associated with TRPC channel activation and alterations in membrane potential and Ca2+i dynamics.



Circ Arrhythm Electrophysiol: 30 Jan 2021; 14:e009291
Siri-Angkul N, Song Z, Fefelova N, Gwathmey JK, ... Chattipakorn N, Xie LH
Circ Arrhythm Electrophysiol: 30 Jan 2021; 14:e009291 | PMID: 33417472
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Abstract

Recording Intrinsic Nerve Activity at the Sinoatrial Node in Normal Dogs With High-Density Mapping.

Yang Y, Yuan Y, Wong J, Fishbein MC, Chen PS, Everett TH
Background
It is known that autonomic nerve activity controls the sinus rate. However, the coupling between local nerve activity and electrical activation at the sinoatrial node (SAN) remains unclear. We hypothesized that we would be able to record nerve activity at the SAN to investigate if right stellate ganglion (RSG) activation can increase the local intrinsic nerve activity, accelerate sinus rate, and change the earliest activation sites.
Methods
High-density mapping of the epicardial surface of the right atrium including the SAN was performed in 6 dogs during stimulation of the RSG and after RSG stellectomy. A radio transmitter was implanted into 3 additional dogs to record RSG and local nerve activity at the SAN.
Results
Heart rate accelerated from 108±4 bpm at baseline to 125±7 bpm after RSG stimulation (P=0.001), and to 132±7 bpm after apamin injection (P<0.001). Both electrical RSG stimulation and apamin injection induced local nerve activity at the SAN with the average amplitudes of 3.60±0.72 and 3.86±0.56 μV, respectively. RSG stellectomy eliminated the local nerve activity and decreased the heart rate. In ambulatory dogs, local nerve activity at the SAN had a significantly higher average Pearson correlation to heart rate (0.72±0.02, P=0.001) than RSG nerve activity to HR (0.45±0.04, P=0.001).
Conclusions
Local intrinsic nerve activity can be recorded at the SAN. Short bursts of these local nerve activities are present before each atrial activation during heart rate acceleration induced by stimulation of the RSG.



Circ Arrhythm Electrophysiol: 30 Jan 2021; 14:e008610
Yang Y, Yuan Y, Wong J, Fishbein MC, Chen PS, Everett TH
Circ Arrhythm Electrophysiol: 30 Jan 2021; 14:e008610 | PMID: 33417471
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Abstract

Guideline-Concordant Antiarrhythmic Drug Use in the Get With The Guidelines-Atrial Fibrillation Registry.

Field ME, Holmes DN, Page RL, Fonarow GC, ... Piccini JP, Get With The Guidelines-AFIB Clinical Working Group and Hospitals
Background
Antiarrhythmic drug (AAD) therapy for atrial fibrillation (AF) can be associated with both proarrhythmic and noncardiovascular toxicities. Practice guidelines recommend tailored AAD therapy for AF based on patient-specific characteristics, such as coronary artery disease and heart failure, to minimize adverse events. However, current prescription patterns for specific AADs and the degree to which these guidelines are followed in practice are unknown.
Methods
Patients enrolled in the Get With The Guidelines-Atrial Fibrillation registry with a primary diagnosis of AF discharged on an AAD between January 2014 and November 2018 were included. We analyzed rates of prescription of each AAD in several subgroups including those without structural heart disease. We classified AAD use as guideline concordant or nonguideline concordant based on 6 criteria derived from the American Heart Association/American College of Cardiology/Heart Rhythm Society AF guidelines. Guideline concordance for amiodarone was not considered applicable, since its use is not specifically contraindicated in the guidelines for reasons such as structural heart disease or renal function. We analyzed guideline-concordant AAD use by specific patient and hospital characteristics, and regional and temporal trends.
Results
Among 21 921 patients from 123 sites, the median age was 69 years, 46% female and 51% had paroxysmal AF. The most commonly prescribed AAD was amiodarone (38%). Sotalol (23.2%) and dofetilide (19.2%) were each more commonly prescribed than either flecainide (9.8%) or propafenone (4.8%). Overall guideline-concordant AAD prescription at discharge was 84%. Guideline-concordant AAD use by drug was as follows: dofetilide 93%, sotalol 66%, flecainide 68%, propafenone 48%, and dronedarone 80%. There was variability in rate of guideline-concordant AAD use by hospital and geographic region.
Conclusions
Amiodarone remains the most commonly prescribed AAD for AF followed by sotalol and dofetilide. Rates of guideline-concordant AAD use were high, and there was significant variability by specific drugs, hospitals, and regions, highlighting opportunities for additional quality improvement.



Circ Arrhythm Electrophysiol: 30 Jan 2021; 14:e008961
Field ME, Holmes DN, Page RL, Fonarow GC, ... Piccini JP, Get With The Guidelines-AFIB Clinical Working Group and Hospitals
Circ Arrhythm Electrophysiol: 30 Jan 2021; 14:e008961 | PMID: 33419385
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Abstract

Long-Term Safety and Feasibility of Left Bundle Branch Pacing in a Large Single-Center Study.

Su L, Wang S, Wu S, Xu L, ... Whinnett ZI, Huang W
Background
Left bundle branch pacing (LBBP) is a novel pacing method and has been observed to have low and stable pacing thresholds in prior small short-term studies. The objective of this study was to evaluate the feasibility and safety of LBBP in a large consecutive diverse group of patients with long-term follow-up.
Methods
This study prospectively enrolled 632 consecutive pacemaker patients with attempted LBBP from April 2017 to July 2019. Pacing parameters, complications, ECG, and echocardiographic measurements were assessed at implant and during follow-up of 1, 6, 12, and 24 months.
Results
LBBP was successful in 618/632 (97.8%) patients according to strict criteria for LBB capture. Mean follow-up time was 18.6±6.7 months. Two hundred thirty-one patients had follow-up over 2 years. LBB capture threshold at implant was 0.65±0.27 mV at 0.5 ms and 0.69±0.24 mV at 0.5 ms at 2-year follow-up. A significant decrease in QRS duration was observed in patients with left bundle branch block (167.22±18.99 versus 124.02±24.15 ms, P<0.001). Postimplantation left ventricular ejection fraction improved in patients with QRS≥120 ms (48.82±17.78% versus 58.12±13.04%, P<0.001). The number of patients with moderate and severe tricuspid regurgitation decreased at 1 year. Permanent right bundle branch injury occurred in 55 (8.9%) patients. LBB capture threshold increased to >3 V or loss of bundle capture in 6 patients (1%), 2 patients of them had a loss of conduction system capture. Two patients required lead revision due to dislodgement.
Conclusions
This large observational study suggests that LBBP is feasible with high success rates and low complication rates during long-term follow-up. Therefore, LBBP appears to be a reliable method for physiological pacing for patients with either a bradycardia or heart failure pacing indication.



Circ Arrhythm Electrophysiol: 30 Jan 2021; 14:e009261
Su L, Wang S, Wu S, Xu L, ... Whinnett ZI, Huang W
Circ Arrhythm Electrophysiol: 30 Jan 2021; 14:e009261 | PMID: 33426907
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Abstract

2021 ISHNE/HRS/EHRA/APHRS Expert Collaborative Statement on mHealth in Arrhythmia Management: Digital Medical Tools for Heart Rhythm Professionals: From the International Society for Holter and Noninvasive Electrocardiology/Heart Rhythm Society/European Heart Rhythm Association/Asia-Pacific Heart Rhythm Society.

Varma N, Cygankiewicz I, Turakhia MP, Heidbuchel H, ... Steinberg JS, Svennberg E
This collaborative statement from the International Society for Holter and Noninvasive Electrocardiology/Heart Rhythm Society/European Heart Rhythm Association/Asia-Pacific Heart Rhythm Society describes the current status of mobile health technologies in arrhythmia management. The range of digital medical tools and heart rhythm disorders that they may be applied to and clinical decisions that may be enabled are discussed. The facilitation of comorbidity and lifestyle management (increasingly recognized to play a role in heart rhythm disorders) and patient self-management are novel aspects of mobile health. The promises of predictive analytics but also operational challenges in embedding mobile health into routine clinical care are explored.



Circ Arrhythm Electrophysiol: 30 Jan 2021; 14:e009204
Varma N, Cygankiewicz I, Turakhia MP, Heidbuchel H, ... Steinberg JS, Svennberg E
Circ Arrhythm Electrophysiol: 30 Jan 2021; 14:e009204 | PMID: 33573393
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Abstract

Arrhythmias in Cardiac Sarcoidosis Bench to Bedside: A Case-Based Review.

Rosenfeld LE, Chung MK, Harding CV, Spagnolo P, ... Farr MA, Estep JD
Cardiac sarcoidosis is a component of an often multiorgan granulomatous disease of still uncertain cause. It is being recognized with increasing frequency, mainly as the result of heightened awareness and new diagnostic tests, specifically cardiac magnetic resonance imaging and 18F-fluorodeoxyglucose positron emission tomography scans. The purpose of this case-based review is to highlight the potentially life-saving importance of making the early diagnosis of cardiac sarcoidosis using these new tools and to provide a framework for the optimal care of patients with this disease. We will review disease mechanisms as currently understood, associated arrhythmias including conduction abnormalities, and atrial and ventricular tachyarrhythmias, guideline-directed diagnostic criteria, screening of patients with extracardiac sarcoidosis, and the use of pacemakers and defibrillators in this setting. Treatment options, including those related to heart failure, and those which may help clarify disease mechanisms are included.



Circ Arrhythm Electrophysiol: 30 Jan 2021; 14:e009203
Rosenfeld LE, Chung MK, Harding CV, Spagnolo P, ... Farr MA, Estep JD
Circ Arrhythm Electrophysiol: 30 Jan 2021; 14:e009203 | PMID: 33591816
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Abstract

Anatomical Predictors of Pacemaker Dependency After Transcatheter Aortic Valve Replacement.

Nai Fovino L, Cipriani A, Fabris T, Massussi M, ... Fraccaro C, Tarantini G
Background
Conduction disturbances after transcatheter aortic valve replacement (TAVR) are often transient. Limited data exist on anatomic factors predisposing to pacemaker dependency after TAVR. We sought to assess the rate and the possible predictors of pacemaker dependency after TAVR.
Methods
Consecutive patients undergoing pacemaker implantation up to 30 days after TAVR between May 2014 and September 2019 were included. Baseline electrocardiographic, computed tomography, and procedural characteristics were collected, including valve implantation depth and membranous septum length, an anatomic surrogate of the distance between the aortic annulus and the His bundle. Pacemaker dependency at 30 days and 1 year and all-cause mortality during follow-up were evaluated.
Results
Of 728 TAVR patients, 112 (53.5% men; median age, 81 years) underwent pacemaker implantation after TAVR. Of these, 44.6% (50 of 112) were pacemaker dependent at 30 days and 46.7% (36 of 77) at 1 year. By multivariate analysis, independent predictors of 30-day pacemaker dependency included left ventricular outflow tract calcifications under the left coronary cusp (odds ratio, 5.69 [95% CI, 1.45-22.31]; P=0.013) and a difference between membranous septum length and implantation depth (ΔMSID) ≥3 mm (odds ratio, 7.58 [95% CI, 2.07-27.78]; P=0.002). Conversely, membranous septum length and implantation depth alone were not associated with pacemaker dependency (odds ratio, 0.79 [95% CI, 0.60-1.05]; P=0.11 and odds ratio, 1.11 [95% CI, 0.99-1.24]; P=0.08). At a median follow-up of 28.1 (11.7-48.6) months, pacemaker-dependent patients did not show a worse survival (P=0.26).
Conclusions
Less than half of the patients undergoing pacemaker implantation after TAVR are pacemaker-dependent at midterm follow-up. ΔMSID ≥3 mm and the presence of left ventricular outflow tract calcifications under the left coronary cusp, but not membranous septum length nor implantation depth alone, are predictive of long-term pacemaker dependency after TAVR, thus influencing device selection and programming.



Circ Arrhythm Electrophysiol: 30 Dec 2020; 14:e009028
Nai Fovino L, Cipriani A, Fabris T, Massussi M, ... Fraccaro C, Tarantini G
Circ Arrhythm Electrophysiol: 30 Dec 2020; 14:e009028 | PMID: 33306415
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Abstract

Sudden Cardiac Death Prediction in Arrhythmogenic Right Ventricular Cardiomyopathy: A Multinational Collaboration.

Cadrin-Tourigny J, Bosman LP, Wang W, Tadros R, ... Te Riele ASJM, James CA
Background
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is associated with ventricular arrhythmias (VA) and sudden cardiac death (SCD). A model was recently developed to predict incident sustained VA in patients with ARVC. However, since this outcome may overestimate the risk for SCD, we aimed to specifically predict life-threatening VA (LTVA) as a closer surrogate for SCD.
Methods
We assembled a retrospective cohort of definite ARVC cases from 15 centers in North America and Europe. Association of 8 prespecified clinical predictors with LTVA (SCD, aborted SCD, sustained, or implantable cardioverter-defibrillator treated ventricular tachycardia >250 beats per minute) in follow-up was assessed by Cox regression with backward selection. Candidate variables included age, sex, prior sustained VA (≥30s, hemodynamically unstable, or implantable cardioverter-defibrillator treated ventricular tachycardia; or aborted SCD), syncope, 24-hour premature ventricular complexes count, the number of anterior and inferior leads with T-wave inversion, left and right ventricular ejection fraction. The resulting model was internally validated using bootstrapping.
Results
A total of 864 patients with definite ARVC (40±16 years; 53% male) were included. Over 5.75 years (interquartile range, 2.77-10.58) of follow-up, 93 (10.8%) patients experienced LTVA including 15 with SCD/aborted SCD (1.7%). Of the 8 prespecified clinical predictors, only 4 (younger age, male sex, premature ventricular complex count, and number of leads with T-wave inversion) were associated with LTVA. Notably, prior sustained VA did not predict subsequent LTVA (P=0.850). A model including only these 4 predictors had an optimism-corrected C-index of 0.74 (95% CI, 0.69-0.80) and calibration slope of 0.95 (95% CI, 0.94-0.98) indicating minimal over-optimism.
Conclusions
LTVA events in patients with ARVC can be predicted by a novel simple prediction model using only 4 clinical predictors. Prior sustained VA and the extent of functional heart disease are not associated with subsequent LTVA events.



Circ Arrhythm Electrophysiol: 30 Dec 2020; 14:e008509
Cadrin-Tourigny J, Bosman LP, Wang W, Tadros R, ... Te Riele ASJM, James CA
Circ Arrhythm Electrophysiol: 30 Dec 2020; 14:e008509 | PMID: 33296238
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Abstract

Heart Size Corrected Electrical Dyssynchrony and Its Impact on Sex-Specific Response to Cardiac Resynchronization Therapy.

Salden OAE, van Stipdonk AMW, den Ruijter HM, Cramer MJ, ... Vernooy K, Meine M
Background
Women are less likely to receive cardiac resynchronization therapy, yet, they are more responsive to the therapy and respond at shorter QRS duration. The present study hypothesized that a relatively larger left ventricular (LV) electrical dyssynchrony in smaller hearts contributes to the better cardiac resynchronization therapy response in women. For this, the vectorcardiography-derived QRS area is used, since it allows for a more detailed quantification of electrical dyssynchrony compared with conventional electrocardiographic markers.
Methods
Data from a multicenter registry of 725 cardiac resynchronization therapy patients (median follow-up, 4.2 years [interquartile range, 2.7-6.1]) were analyzed. Baseline electrical dyssynchrony was evaluated using the QRS area and the corrected QRS area for heart size using the LV end-diastolic volume (QRSarea/LVEDV). Impact of the QRSarea/LVEDV ratio on the association between sex and LV reverse remodeling (LV end-systolic volume change) and sex and the composite outcome of all-cause mortality, LV assist device implantation, or heart transplantation was assessed.
Results
At baseline, women (n=228) displayed larger electrical dyssynchrony than men (QRS area, 132±55 versus 123±58 μVs; P=0.043), which was even more pronounced for the QRSarea/LVEDV ratio (0.76±0.46 versus 0.57±0.34 μVs/mL; P<0.001). After multivariable analyses, female sex was associated with LV end-systolic volume change (β=0.12; P=0.003) and a lower occurrence of the composite outcome (hazard ratio, 0.59 [0.42-0.85]; P=0.004). A part of the female advantage regarding reverse remodeling was attributed to the larger QRSarea/LVEDV ratio in women (25-fold change in β from 0.12 to 0.09). The larger QRSarea/LVEDV ratio did not contribute to the better survival observed in women. In both volumetric responders and nonresponders, female sex remained strongly associated with a lower risk of the composite outcome (adjusted hazard ratio, 0.59 [0.36-0.97]; P=0.036; and 0.55 [0.33-0.90]; P=0.018, respectively).
Conclusions
Greater electrical dyssynchrony in smaller hearts contributes, in part, to more reverse remodeling observed in women after cardiac resynchronization therapy, but this does not explain their better long-term outcomes.



Circ Arrhythm Electrophysiol: 30 Dec 2020; 14:e008452
Salden OAE, van Stipdonk AMW, den Ruijter HM, Cramer MJ, ... Vernooy K, Meine M
Circ Arrhythm Electrophysiol: 30 Dec 2020; 14:e008452 | PMID: 33296227
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Abstract

Performance of Atrial Fibrillation Risk Prediction Models in Over 4 Million Individuals.

Khurshid S, Kartoun U, Ashburner JM, Trinquart L, ... Ng K, Lubitz SA
Background
Atrial fibrillation (AF) is associated with increased risks of stroke and heart failure. Electronic health record (EHR)-based AF risk prediction may facilitate efficient deployment of interventions to diagnose or prevent AF altogether.
Methods
We externally validated an electronic health record AF (EHR-AF) score in IBM Explorys Life Sciences, a multi-institutional dataset containing statistically deidentified EHR data for over 21 million individuals (Explorys Dataset). We included individuals with complete AF risk data, ≥2 office visits within 2 years, and no prevalent AF. We compared EHR-AF to existing scores including CHARGE-AF (Cohorts for Heart and Aging Research in Genomic Epidemiology Atrial Fibrillation), C2HEST (coronary artery disease or chronic obstructive pulmonary disease, hypertension, elderly, systolic heart failure, thyroid disease), and CHA2DS2-VASc. We assessed association between AF risk scores and 5-year incident AF, stroke, and heart failure using Cox proportional hazards modeling, 5-year AF discrimination using C indices, and calibration of predicted AF risk to observed AF incidence.
Results
Of 21 825 853 individuals in the Explorys Dataset, 4 508 180 comprised the analysis (age 62.5, 56.3% female). AF risk scores were strongly associated with 5-year incident AF (hazard ratio per SD increase 1.85 using CHA2DS2-VASc to 2.88 using EHR-AF), stroke (1.61 using C2HEST to 1.92 using CHARGE-AF), and heart failure (1.91 using CHA2DS2-VASc to 2.58 using EHR-AF). EHR-AF (C index, 0.808 [95% CI, 0.807-0.809]) demonstrated favorable AF discrimination compared to CHARGE-AF (0.806 [95% CI, 0.805-0.807]), C2HEST (0.683 [95% CI, 0.682-0.684]), and CHA2DS2-VASc (0.720 [95% CI, 0.719-0.722]). Of the scores, EHR-AF demonstrated the best calibration to incident AF (calibration slope, 1.002 [95% CI, 0.997-1.007]). In subgroup analyses, AF discrimination using EHR-AF was lower in individuals with stroke (C index, 0.696 [95% CI, 0.692-0.700]) and heart failure (0.621 [95% CI, 0.617-0.625]).
Conclusions
EHR-AF demonstrates predictive accuracy for incident AF using readily ascertained EHR data. AF risk is associated with incident stroke and heart failure. Use of such risk scores may facilitate decision support and population health management efforts focused on minimizing AF-related morbidity.



Circ Arrhythm Electrophysiol: 30 Dec 2020; 14:e008997
Khurshid S, Kartoun U, Ashburner JM, Trinquart L, ... Ng K, Lubitz SA
Circ Arrhythm Electrophysiol: 30 Dec 2020; 14:e008997 | PMID: 33295794
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Abstract

Positive Clinical Benefit on Patient Care, Quality of Life, and Symptoms After Contact Force-Guided Radiofrequency Ablation in Persistent Atrial Fibrillation: Analyses From the PRECEPT Prospective Multicenter Study.

Natale A, Calkins H, Osorio J, Pollak SJ, ... Mansour M, PRECEPT Investigators
Background
There is limited evidence on the long-term clinical benefits of catheter ablation in patients with persistent atrial fibrillation.
Methods
PRECEPT was a prospective, multicenter, single-arm Food and Drug Administration-regulated investigational device exemption clinical study. Patients were followed up to 15 months after ablation. Outcomes included use of antiarrhythmic drugs, rate of cardioversions and cardiovascular hospitalization, Atrial Fibrillation Effect on Quality-of-Life score, and Canadian Cardiovascular Society Severity of Atrial Fibrillation score.
Results
A total of 333 enrolled persistent atrial fibrillation patients underwent ablation. The cardioversion rate decreased by 83% at the 9- to 15-month follow-up. Antiarrhythmic drug utilization decreased by 69% at 12 to 15 months post-ablation. The Kaplan-Meier estimate of freedom from cardiovascular hospitalization was 84.2% (95% CI, 80.2%-88.2%) at 15 months. Consistent improvements in mean Atrial Fibrillation Effect on Quality-of-Life composite (+50.0) were seen at 6 months, sustained at 15 months, and exceeded the minimum clinically important difference. Improvements in Atrial Fibrillation Effect on Quality-of-Life scores were significantly better among participants without documented atrial arrhythmia recurrences. By Canadian Cardiovascular Society Severity of Atrial Fibrillation symptom classification, >80% of patients were asymptomatic (class 0) at 15 months post-ablation compared with only 0.7% at baseline.
Conclusions
Contact force-guided radiofrequency ablation of persistent atrial fibrillation was associated with a significant decrease in antiarrhythmic drug use, cardioversion rate, and hospitalization. Clinically meaningful improvements in quality of life were observed in all patients. The majority of the patients (>80%) were asymptomatic at 15 months post-ablation. The positive clinical impact of improved quality of life and reduced health care utilization may help with shared decision-making in persistent atrial fibrillation treatment. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02817776.



Circ Arrhythm Electrophysiol: 30 Dec 2020; 14:e008867
Natale A, Calkins H, Osorio J, Pollak SJ, ... Mansour M, PRECEPT Investigators
Circ Arrhythm Electrophysiol: 30 Dec 2020; 14:e008867 | PMID: 33290093
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Abstract

Remote Monitoring With Appropriate Reaction to Alerts Was Associated With Improved Outcomes in Chronic Heart Failure: Results From the OptiLink HF Study.

Wintrich J, Pavlicek V, Brachmann J, Bosch R, ... Böhm M, Ukena C
Background
Impedance-based remote monitoring (RM) failed to reduce clinical events in the OptiLink heart failure (HF) trial. However, rates of alert-driven interventions triggered by intrathoracic fluid index threshold crossings (FTC) were low indicating physicians\' inappropriate reactions to alerts.
Methods
We separated appropriate from inappropriate contacts to FTC transmissions in the OptiLink HF trial (Optimization of Heart Failure Management Using OptiVol™ Fluid Status Monitoring and CareLink™). Appropriate contacts had to meet the following criteria: (1) initial telephone contact within 2 working days after FTC transmission, (2) follow-up contacts according to study protocol, and (3) medical intervention initiated after FTC due to cardiac decompensation. We compared time to cardiovascular death or HF hospitalization between RM patients contacted appropriately or inappropriately and patients with usual care.
Results
In the RM group, at least one FTC alert was transmitted in 356 patients (70.5%; n=505). Of note, only 55.5% (n=758) of all transmitted FTCs (n=1365) were followed by an appropriate contact. While 113 patients (31.7%; n=356) have been contacted appropriately after every FTC, in 243 patients (68.3%; n=356) at least one FTC was not responded by an appropriate contact. Compared with usual care, RM with appropriate contacts to FTC alerts independently reduced the risk of the primary end point (hazard ratio, 0.61 [95% CI, 0.39-0.95]; P=0.027).
Conclusions
RM appropriate reactions to FTC alerts are associated with significantly improved clinical outcomes in patients with advanced HF and implantable cardioverter-defibrillators.



Circ Arrhythm Electrophysiol: 30 Dec 2020; 14:e008693
Wintrich J, Pavlicek V, Brachmann J, Bosch R, ... Böhm M, Ukena C
Circ Arrhythm Electrophysiol: 30 Dec 2020; 14:e008693 | PMID: 33301362
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Abstract

PRECAF Randomized Controlled Trial.

Kuo L, Frankel DS, Lin A, Arkles J, ... Marchlinski FE, Nazarian S
Background
We have previously shown that the presence of dual muscular coronary sinus (CS) to left atrial (LA) connections, coupled with rate-dependent unidirectional block in one limb, is associated with atrial fibrillation (AF) induction. This study sought to examine whether ablation of distal CS to LA connections at a first AF ablation reduces arrhythmia recurrence during follow-up.
Methods
In this single-center, randomized, controlled trial, 35 consecutive patients with drug-refractory AF undergoing first-time ablation between August 2018 and August 2019, were randomly assigned to (1) standard ablation (pulmonary vein isolation and nonpulmonary vein trigger ablation) versus (2) standard ablation plus elimination of distal CS to LA connections targeting the earliest LA activation during distal CS pacing with a deca-polar catheter placed with its proximal electrode at the ostium. Change of the local CS atrial electrogram and LA activation sequence to early activation of the LA septum or roof during distal CS pacing were the end point for CS-LA connection elimination.
Results
Thirty patients completed 6 months study follow-up (15 patients in each group). Demographic characteristics including age and AF persistence were similar in both groups. After a mean follow-up of 170±22 days, there were 7 atrial arrhythmia recurrences in the standard group and 1 recurrence in the CS-LA connection elimination group (46.7% versus 6.7%, hazard ratio, 0.12, P=0.047).
Conclusions
Elimination of distal CS to LA connections reduced atrial arrhythmia recurrences compared with standard pulmonary vein isolation and nonpulmonary vein trigger ablation in patients undergoing a first AF ablation procedure in a small randomized study. This strategy warrants further evaluation in a multicenter randomized trial. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03646643.



Circ Arrhythm Electrophysiol: 30 Dec 2020; 14:e008993
Kuo L, Frankel DS, Lin A, Arkles J, ... Marchlinski FE, Nazarian S
Circ Arrhythm Electrophysiol: 30 Dec 2020; 14:e008993 | PMID: 33301361
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Abstract

Circadian Pattern of Ion Channel Gene Expression in Failing Human Hearts.

McTiernan CF, Lemster BH, Bedi KC, Margulies KB, ... Shusterman V, Saba S
Background
Ventricular tachyarrhythmias and sudden cardiac death show a circadian pattern of occurrence in patients with heart failure. In the rodent ventricle, a significant portion of genes, including some ion channels, shows a circadian pattern of expression. However, genes that define electrophysiological properties in failing human heart ventricles have not been examined for a circadian expression pattern.
Methods
Ventricular tissue samples were collected from patients at the time of cardiac transplantation. Two sets of samples (n=37 and 46, one set with a greater arrhythmic history) were selected to generate pseudo-time series according to their collection time. A third set (n=27) of samples was acquired from the nonfailing ventricles of brain-dead donors. The expression of 5 known circadian clock genes and 19 additional ion channel genes plausibly important to electrophysiological properties were analyzed by real-time polymerase chain reaction and then analyzed for the percentage of expression variation attributed to a 24-hour circadian pattern.
Results
The 5 known circadian clock gene transcripts showed a strong circadian expression pattern. Compared with rodent hearts, the human circadian clock gene transcripts showed a similar temporal order of acrophases but with a ≈7.6 hours phase shift. Five of the ion channel genes also showed strong circadian expression. Comparable studies of circadian clock gene expression in samples recovered from nonheart failure brain-dead donors showed acrophase shifts, or weak or complete loss of circadian rhythmicity, suggesting alterations in circadian gene expression.
Conclusions
Ventricular tissue from failing human hearts display a circadian pattern of circadian clock gene expression but phase-shifted relative to rodent hearts. At least 5 ion channels show a circadian expression pattern in the ventricles of failing human hearts, which may underlie a circadian pattern of ventricular tachyarrhythmia/sudden cardiac death. Nonfailing hearts from brain-dead donors show marked differences in circadian clock gene expression patterns, suggesting fundamental deviations from circadian expression.



Circ Arrhythm Electrophysiol: 30 Dec 2020; 14:e009254
McTiernan CF, Lemster BH, Bedi KC, Margulies KB, ... Shusterman V, Saba S
Circ Arrhythm Electrophysiol: 30 Dec 2020; 14:e009254 | PMID: 33301345
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Abstract

Prospective Randomized Evaluation of High Power During CLOSE-Guided Pulmonary Vein Isolation: The POWER-AF Study.

Wielandts JY, Kyriakopoulou M, Almorad A, Hilfiker G, ... Duytschaever M, Knecht S
Background
CLOSE-guided atrial fibrillation (AF) ablation is based on contiguous (intertag distance ≤6 mm), optimized (Ablation Index >550 anteriorly and >400 posteriorly) point-by-point radiofrequency lesions. The optimal radiofrequency power remains unknown.
Methods
The POWER-AF study is a prospective, randomized controlled monocentric study including patients with paroxysmal AF, planned for first CLOSE-guided pulmonary vein isolation using a contact force radiofrequency catheter (Thermocool SmartTouch, Biosense Webster, Inc, Irvine, CA). A total of 100 patients were randomized into 2 groups (1:1). The control group received AF ablation using the standard CLOSE protocol (35 W), whereas in the experimental group, pulmonary vein isolation was performed using high power (45 W). Endoscopic evaluation was performed in patients with intraesophageal temperature rise >38.5 °C.
Results
The resulting sample size was 96 (48+48) patients. In the high power group, shorter procedure time (80 versus 102 minutes, P<0.001), shorter total radiofrequency application time (16 versus 26 minutes, P<0.001), and radiofrequency time per application (26 versus 37 s anteriorly, P<0.001 and 13 versus 17 s posteriorly, P<0.001) were observed. Endoscopic evaluation (performed in 19/48 versus 25/48 patients respectively, P=0.31) showed an ulcerative perforation in a high power group patient (treated by endoscopic stenting and normalization after ≈4 months) and a superficial ulcerative lesion in a control group patient (conservative treatment). Both occurred following excessive Ablation Index applications (up to 460 and 480, respectively) with excessive contact force (30 g on average, with peaks up to 50 g). Six-months AF recurrence was not significantly different (10% in high power versus 8% in control, P=0.74).
Conclusions
This randomized controlled study shows that a 45 W radiofrequency power CLOSE protocol in patients with paroxysmal AF significantly increases the global procedural efficiency with similar midterm efficacy. However, our study showed a narrower safety margin and a limited increased efficiency at the posterior wall using high power. This advocates against the use of high power in the region neighboring the esophagus.



Circ Arrhythm Electrophysiol: 30 Dec 2020; 14:e009112
Wielandts JY, Kyriakopoulou M, Almorad A, Hilfiker G, ... Duytschaever M, Knecht S
Circ Arrhythm Electrophysiol: 30 Dec 2020; 14:e009112 | PMID: 33300809
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Abstract

Surveys and Registries on Catheter Ablation of Atrial Fibrillation: Fifteen Years of History.

Cappato R, Ali H
Surveys and registries are widely used in medicine as valuable tools to integrate the information from randomized and observational studies. Early after its introduction in daily practice and parallel to its escalating popularity, catheter ablation of atrial fibrillation has been the subject of several surveys and registries. Over the years, relevant aspects associated with atrial fibrillation ablation have been investigated using these tools, including procedural safety and efficacy, discontinuation of anticoagulation therapy and risk of stroke postablation, and outcomes in special populations. The aim of this article is to provide a comprehensive review of the contributions offered by surveys and registries in catheter ablation of atrial fibrillation over the past 15 years.



Circ Arrhythm Electrophysiol: 30 Dec 2020; 14:e008073
Cappato R, Ali H
Circ Arrhythm Electrophysiol: 30 Dec 2020; 14:e008073 | PMID: 33441001
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Impact:

This program is still in alpha version.