Progression of Atrial Fibrillation after Cryoablation or Drug Therapy.

BACKGROUND: Atrial fibrillation is a chronic, progressive disorder, and persistent forms of atrial fibrillation are associated with increased risks of thromboembolism and heart failure. Catheter ablation as initial therapy may modify the pathogenic mechanism of atrial fibrillation and alter progression to persistent atrial fibrillation. METHODS: We report the 3-year follow-up of patients with paroxysmal, untreated atrial fibrillation who were enrolled in a trial in which they had been randomly assigned to undergo initial rhythm-control therapy with cryoballoon ablation or to receive antiarrhythmic drug therapy. All the patients had implantable loop recorders placed at the time of trial entry, and evaluation was conducted by means of downloaded daily recordings and in-person visits every 6 months. Data regarding the first episode of persistent atrial fibrillation (lasting ≥7 days or lasting 48 hours to 7 days but requiring cardioversion for termination), recurrent atrial tachyarrhythmia (defined as atrial fibrillation, flutter, or tachycardia lasting ≥30 seconds), the burden of atrial fibrillation (percentage of time in atrial fibrillation), quality-of-life metrics, health care utilization, and safety were collected. RESULTS: A total of 303 patients were enrolled, with 154 patients assigned to undergo initial rhythm-control therapy with cryoballoon ablation and 149 assigned to receive antiarrhythmic drug therapy. Over 36 months of follow-up, 3 patients (1.9%) in the ablation group had an episode of persistent atrial fibrillation, as compared with 11 patients (7.4%) in the antiarrhythmic drug group (hazard ratio, 0.25; 95% confidence interval [CI], 0.09 to 0.70). Recurrent atrial tachyarrhythmia occurred in 87 patients in the ablation group (56.5%) and in 115 in the antiarrhythmic drug group (77.2%) (hazard ratio, 0.51; 95% CI, 0.38 to 0.67). The median percentage of time in atrial fibrillation was 0.00% (interquartile range, 0.00 to 0.12) in the ablation group and 0.24% (interquartile range, 0.01 to 0.94) in the antiarrhythmic drug group. At 3 years, 8 patients (5.2%) in the ablation group and 25 (16.8%) in the antiarrhythmic drug group had been hospitalized (relative risk, 0.31; 95% CI, 0.14 to 0.66). Serious adverse events occurred in 7 patients (4.5%) in the ablation group and in 15 (10.1%) in the antiarrhythmic drug group. CONCLUSIONS: Initial treatment of paroxysmal atrial fibrillation with catheter cryoballoon ablation was associated with a lower incidence of persistent atrial fibrillation or recurrent atrial tachyarrhythmia over 3 years of follow-up than initial use of antiarrhythmic drugs. (Funded by the Cardiac Arrhythmia Network of Canada and others; EARLY-AF ClinicalTrials.gov number, NCT02825979.).

Atrial fibrillation progression after cryoablation vs. radiofrequency ablation: the CIRCA-DOSE trial.

BACKGROUND AND AIMS: Atrial fibrillation (AF) is a chronic progressive disorder. Persistent forms of AF are associated with increased rates of thromboembolism, heart failure, and death. Catheter ablation modifies the pathogenic mechanism of AF progression. No randomized studies have evaluated the impact of the ablation energy on progression to persistent atrial tachyarrhythmia. METHODS: Three hundred forty-six patients with drug-refractory paroxysmal AF were enrolled and randomly assigned to contact-force-guided RF ablation (CF-RF ablation, 115), 4 min cryoballoon ablation (CRYO-4, 115), or 2 min cryoballoon ablation (CRYO-2, 116). Implantable cardiac monitors placed at study entry were used for follow-up. The main outcome was the first episode of persistent atrial tachyarrhythmia. Secondary outcomes included atrial tachyarrhythmia recurrence and arrhythmia burden on the implantable monitor. RESULTS: At a median of 944.0 (interquartile range [IQR], 612.5-1104) days, 0 of 115 patients (0.0%) randomly assigned to CF-RF, 8 of 115 patients (7.0%) assigned to CRYO-4, and 5 of 116 patients (4.3%) assigned to CRYO-2 experienced an episode of persistent atrial tachyarrhythmia (P = .03). A documented recurrence of any atrial tachyarrhythmia ≥30 s occurred in 56.5%, 53.9%, and 62.9% of those randomized to CF-RF, CRYO-4, and CRYO-2, respectively; P = .65. Compared with that of the pre-ablation monitoring period, AF burden was reduced by a median of 99.5% (IQR 94.0%, 100.0%) with CF-RF, 99.9% (IQR 93.3%-100.0%) with CRYO-4, and 99.1%% (IQR 87.0%-100.0%) with CRYO-2 (P = .38). CONCLUSIONS: Catheter ablation of paroxysmal AF using radiofrequency energy was associated with fewer patients developing persistent AF on follow-up.

Cryoablation or Drug Therapy for Initial Treatment of Atrial Fibrillation.

BACKGROUND: Guidelines recommend a trial of one or more antiarrhythmic drugs before catheter ablation is considered in patients with atrial fibrillation. However, first-line ablation may be more effective in maintaining sinus rhythm. METHODS: We randomly assigned 303 patients with symptomatic, paroxysmal, untreated atrial fibrillation to undergo catheter ablation with a cryothermy balloon or to receive antiarrhythmic drug therapy for initial rhythm control. All the patients received an implantable cardiac monitoring device to detect atrial tachyarrhythmia. The follow-up period was 12 months. The primary end point was the first documented recurrence of any atrial tachyarrhythmia (atrial fibrillation, atrial flutter, or atrial tachycardia) between 91 and 365 days after catheter ablation or the initiation of an antiarrhythmic drug. The secondary end points included freedom from symptomatic arrhythmia, the atrial fibrillation burden, and quality of life. RESULTS: At 1 year, a recurrence of atrial tachyarrhythmia had occurred in 66 of 154 patients (42.9%) assigned to undergo ablation and in 101 of 149 patients (67.8%) assigned to receive antiarrhythmic drugs (hazard ratio, 0.48; 95% confidence interval [CI], 0.35 to 0.66; P<0.001). Symptomatic atrial tachyarrhythmia had recurred in 11.0% of the patients who underwent ablation and in 26.2% of those who received antiarrhythmic drugs (hazard ratio, 0.39; 95% CI, 0.22 to 0.68). The median percentage of time in atrial fibrillation was 0% (interquartile range, 0 to 0.08) with ablation and 0.13% (interquartile range, 0 to 1.60) with antiarrhythmic drugs. Serious adverse events occurred in 5 patients (3.2%) who underwent ablation and in 6 patients (4.0%) who received antiarrhythmic drugs. CONCLUSIONS: Among patients receiving initial treatment for symptomatic, paroxysmal atrial fibrillation, there was a significantly lower rate of atrial fibrillation recurrence with catheter cryoballoon ablation than with antiarrhythmic drug therapy, as assessed by continuous cardiac rhythm monitoring. (Funded by the Cardiac Arrhythmia Network of Canada and others; EARLY-AF ClinicalTrials.gov number, NCT02825979.).

High-power short-duration versus low-power long-duration ablation for pulmonary vein isolation: A substudy of the AWARE randomized controlled trial.

INTRODUCTION: Pulmonary vein isolations (PVI) are being performed using a high-power, short-duration (HPSD) strategy. The purpose of this study was to compare the clinical efficacy and safety outcomes of an HPSD versus low-power, long-duration (LPLD) approach to PVI in patients with paroxysmal atrial fibrillation (AF). METHODS: Patients were grouped according to a HPSD (≥40 W) or LPLD (≤35 W) strategy. The primary endpoint was the 1-year recurrence of any atrial arrhythmia lasting ≥30 s, detected using three 14-day ambulatory continuous ECG monitoring. Procedural and safety endpoints were also evaluated. The primary analysis were regression models incorporating propensity scores yielding adjusted relative risk (RRa ) and mean difference (MDa ) estimates. RESULTS: Of the 398 patients included in the AWARE Trial, 173 (43%) underwent HPSD and 225 (57%) LPLD ablation. The distribution of power was 50 W in 75%, 45 W in 20%, and 40 W in 5% in the HPSD group, and 35 W with 25 W on the posterior wall in the LPLD group. The primary outcome was not statistically significant at 30.1% versus 22.2% in HPSD and LPLD groups with RRa 0.77 (95% confidence interval [CI]) 0.55-1.10; p = .165). The secondary outcome of repeat catheter ablation was not statistically significant at 6.9% and 9.8% (RRa 1.59 [95% CI 0.77-3.30]; p = .208) respectively, nor was the incidence of any ECG documented AF during the blanking period: 1.7% versus 8.0% (RRa 3.95 [95% CI 1.00-15.61; p = .049) in the HPSD versus LPLD group respectively. The total procedure time was significantly shorter in the HPSD group (MDa 97.5 min [95% CI 84.8-110.4)]; p < .0001) with no difference in adjudicated serious adverse events. CONCLUSIONS: An HPSD strategy was associated with significantly shorter procedural times with similar efficacy in terms of clinical arrhythmia recurrence. Importantly, there was no signal for increased harm with a HPSD strategy.

One-year outcomes of pulmonary vein isolation with a novel cryoballoon: Primary results of the FROZEN AF trial.

INTRODUCTION: Cryoablation therapy for pulmonary vein isolation (PVI) to treat paroxysmal atrial fibrillation (PAF) is well established. A novel 28 mm cryoballoon system designed to operate under low pressure to safely reach a lower nadir temperature and maintain constant balloon size during cooling has not been prospectively studied in a large patient population for safety and efficacy. The FROZEN AF (NCT04133168) trial was an international multicenter, open-label, prospective, single-arm study on the safety and performance of a novel cryoballoon system for treatment of PAF. METHODS AND RESULTS: The study enrolled patients at 44 sites in 10 countries across North America, Europe, and Asia. Subjects were indicated for PVI treatment of PAF and had failed or were intolerant of one or more antiarrhythmic drugs. Procedural outcomes were defined based on the 2017 HRS consensus statement. Follow-up was performed at 7 days, 3, 6, and 12 months. Data are reported as mean ± SD or median (IQR). PVI was performed with a 28 mm cryoballoon in 325 drug refractory PAF patients. Complete PVI was achieved in 95.7% of patients. In cryoablation lesions longer than 60 s, 60.1% of PV isolations required only a single cryoballoon application. Procedure related complications included: phrenic nerve palsy [temporary 4 (1.2%), persistent 0 (0.0%)], cardiac tamponade/perforation 2 (0.6%), and air embolism 1 (0.3%). Freedom from documented atrial arrhythmia recurrence at 12 months was 79.9% (AF 82.7%, AFL 96.5%, AT 98.1%), antiarrhythmic drugs (AAD) were continued or re-initiated in 26.8% of patients after the 3-month blanking period. Additionally, an extension arm enrolled 50 pts for treatment with 28/31 mm variable size cryoballoon. A single temporary PNP occurred in this group, which resolved before discharge. Freedom from documented recurrence at 12 months in these pts was 82.0%. CONCLUSIONS: This novel cryoballoon may facilitate PVI to treat PAF, providing more options to address the variety of anatomies present in patients with PAF. This cryoballoon system proved to be safe and effective for treatment of patients with drug refractory or drug intolerant PAF.

The impact of institutional measures on optimal use of intravenous immunoglobulin.

BACKGROUND: Intravenous immunoglobulin (IVIG) shortage represents an emerging issue in transfusion medicine. Limited data are available to determine effective strategies for optimal use. The objective of this retrospective observational study was to determine the impact of institutional measures on IVIG use at a large academic center. METHODS: IVIG infusions from November 26, 2018 to September 25, 2022 were categorized according to their appropriateness (Recommended, Option of treatment, or Unrecommended), based on provincial guidelines, and separated into three phases: Reference, Transition, and Post-Implementation phases, the latter following the adoption of restrictive measures, including mandatory standardized order forms, a blood bank gatekeeping strategy, and the creation of a stewardship committee. RESULTS: A total of 5431 IVIG infusions were administered to 544 patients, accounting for 295,033 g. The most common indication categories were neurology (30.4%), immunology (29.0%), and hematology (17.4%). From Reference to Post-Implementation phase, IVIG infusions decreased from 2275 to 2000 with unrecommended indications dropping from 9.5% to 7.4% (p = 0.01), and a global reduction of 23.0% (from 131,163 g to 100,936 g of IVIG). Decrease in chronic immunomodulation accounted for 48.3% of total reduction (14,610 g of 30,227 g), whereas single-use immunomodulation, 40.5% (12,237 g of 30,227 g). Moreover, an absolute reduction of 16.9% was observed in orders exceeding the recommended doses (20.8% to 3.9%; p < 0.0001). Together, the unrecommended and excessive IVIG doses decreased from 19,975 g (15.2%) to 6670 g (6.6%). CONCLUSIONS: A global reduction in IVIG use and a preferential decrease in the unrecommended orders were observed, most likely attributable to the bundle of restrictive strategies implemented.

DREAM-ICD-II Study.

BACKGROUND: Regulatory authorities of most industrialized countries recommend 6 months of private driving restriction after implantation of a secondary prevention implantable cardioverter-defibrillator (ICD). These driving restrictions result in significant inconvenience and social implications. This study aimed to assess the incidence rate of appropriate device therapies in contemporary recipients of a secondary prevention ICD. METHODS: This retrospective study at 3 Canadian tertiary care centers enrolled consecutive patients with new secondary prevention ICD implants between 2016 and 2020. RESULTS: For a median of 760 days (324, 1190 days), 721 patients were followed up. The risk of recurrent ventricular arrhythmia was highest during the first 3 months after device insertion (34.4%) and decreased over time (10.6% between 3 and 6 months, 11.7% between 6 and 12 months). The corresponding incidence rate per 100 patient-days was 0.48 (95% CI, 0.35-0.64) at 90 days, 0.28 (95% CI, 0.17-0.45) at 180 days, and 0.21 (95% CI, 0.13-0.33) between 181 and 365 days after ICD insertion (P<0.001). The cumulative incidence of arrhythmic syncope resulting in sudden cardiac incapacitation was 1.8% within the first 90 days and subsequently dropped to 0.4% between 91 and 180 days (P<0.001) after ICD insertion. CONCLUSIONS: The incidence rate of appropriate therapies resulting in sudden cardiac incapacitation in contemporary recipients of a secondary prevention ICD is much lower than previously reported and declines significantly after the first 3 months. Lowering driving restrictions to 3 months after the index cardiac event seems safe, and revision of existing guidelines should be considered in countries still adhering to a 6-month period. Existing restrictions for private driving after implantation of a secondary prevention ICD should be reconsidered.

Novel filamin C (FLNC) variant causes a severe form of familial mixed hypertrophic-restrictive cardiomyopathy.

Variants of filamin C (FLNC) have been identified as rare genetic substrate for hypertrophic cardiomyopathy (HCM). Data on the clinical course of FLNC-related HCM are conflicting with some studies suggesting mild phenotypes whereas other studies have reported more severe outcomes. In this study, we present a novel FLNC variant (Ile1937Asn) that was identified in a large family of French-Canadian descent with excellent segregation data. FLNC-Ile1937Asn is a novel missense variant characterized by full penetrance and poor clinical outcomes. End stage heart failure requiring transplantation occurred in 43% and sudden cardiac death in 29% of affected family members. Other particular features of FLNC-Ile1937Asn include an early disease onset (mean age of 19 years) and the development of a marked atrial myopathy (severe biatrial dilatation with remodeling and multiple complex atrial arrhythmias) that was present in all gene carriers. The FLNC-Ile1937Asn variant is a novel, pathogenic mutation resulting in a severe form of HCM with full disease penetrance. The variant is associated with a high proportion of end-stage heart failure, heart transplantation, and disease-related mortality. Close follow-up and appropriate risk stratification of affected individuals at specialized heart centers is recommended.

Leucocyte-derived micro-RNAs as candidate biomarkers in Brugada syndrome.

AIMS: Risk stratification for sudden cardiac death in patients with Brugada syndrome remains a major challenge. Contemporary risk prediction models have only modest predictive value. The aim of this study was to assess the role of micro-RNAs from peripheral blood as candidate biomarkers in Brugada syndrome. METHODS AND RESULTS: In this prospective study, Brugada patients and unaffected control individuals were enrolled for analysis of leucocyte-derived microRNAs (miRNAs) levels. Expression levels of 798 different circulating miRNAs were analysed on the NanoString® nCounter platform. All results were cross-validated by using a quantitative polymerase chain reaction. Micro-RNA expression levels of Brugada patients were compared with clinical data. A total of 21 definite Brugada patients (38% with a history of ventricular arrhythmia or cardiac arrest) and 30 unaffected control individuals were included in the study. Micro-RNA analysis showed a distinct expression profile in Brugada patients with 42 differentially expressed markers (38 up-regulated, 4 down-regulated miRNAs). The symptom status of Brugada patients was associated with a distinct miRNA signature. Micro-RNAs 145-5p and 585-3p were significantly up-regulated in symptomatic Brugada patients (P = 0.04). Incorporating miRNAs 145-5p and 585-3p into a multivariable model demonstrated significantly increased symptom prediction (area under the curve = 0.96; 95% confidence interval: 0.88-1.00). CONCLUSION: Brugada patients display a distinct miRNA expression profile compared with unaffected control individuals. There is also evidence that certain miRNAs (miR-145-5p and miR-585-3p) are associated with the symptom status of Brugada patients. The results suggest the principal utility of leucocyte-derived miRNAs as prognostic biomarkers for Brugada syndrome.

SCN5A-C683R exhibits combined gain-of-function and loss-of-function properties related to adrenaline-triggered ventricular arrhythmia.

NEW FINDINGS: What is the role of SCN5A-C683R? SCN5A-C683R is a novel variant associated with an uncommon phenotype of adrenaline-triggered ventricular arrhythmia in the absence of a distinct ECG phenotype. What is the main finding and its importance? Functional studies demonstrated that NaV 1.5/C683R results in a mixed electrophysiological phenotype with gain-of-function (GOF) and loss-of-function (LOF) properties compared with NaV 1.5/wild type. Gain-of-function properties are characterized by a significant increase of the maximal current density and a hyperpolarizing shift of the steady-state activation. The LOF effect of NaV 1.5/C683R is characterized by increased closed-state inactivation. Electrophysiological properties and clinical manifestation of SCN5A-C683R are different from long-QT-3 or Brugada syndrome and might represent a distinct inherited arrhythmia syndrome. ABSTRACT: Mutations of SCN5Ahave been identified as the genetic substrate of various inherited arrhythmia syndromes, including long-QT-3 and Brugada syndrome. We recently identified a novel SCN5A variant (C683R) in two genetically unrelated families. The index patients of both families experienced adrenaline-triggered ventricular arrhythmia with cardiac arrest but did not show a specific ECG phenotype, raising the hypothesis that SCN5A-C683R might be a susceptibility variant and the genetic substrate of distinct inherited arrhythmia. We conducted functional cellular studies to characterize the electrophysiological properties of NaV 1.5/C683R in order to explore the potential pathogenicity of this novel variant. The C683R variant was engineered by site-directed mutagenesis. NaV 1.5/wild type (WT) and NaV 1.5/C683R were expressed in tsA201 cells. Electrophysiological characterization of C683R was performed using the whole-cell patch-clamp technique. Adrenergic stimulation was mimicked by exposure to the protein kinase A activator 8-CPT-cAMP. The impact of ß-blockers was tested by exposing NaV 1.5/WT and NaV 1.5/C683R currents to propranolol and nadolol. C683R resulted in a co-association of gain-of-function and loss-of-function properties of NaV 1.5. Gain-of-function properties were characterized by a significant increase of the maximal NaV 1.5 current density compared with NaV 1.5/WT (861 ± 309 vs. 627 ± 489 pA/pF; P < 0.05, n ≥ 9) that was potentiated in NaV 1.5/C683R with 8-CPT-cAMP stimulation (869 ± 287 vs. 607 ± 320 pA/pF; P < 0.05, n ≥ 12). C683R also resulted in a significant hyperpolarizing shift in the voltage of steady-state activation (-65.4 ± 3.0 vs. -57.2 ± 4.8 mV; P < 0.001), resulting in an increased window current compared with WT. The loss-of-function effect of NaV 1.5/C683R was characterized by significantly increased closed-state inactivation compared with NaV 1.5/WT (P < 0.05). C683R is a novel SCN5A variant resulting in a co-association of gain-of-function and loss-of-function properties of the cardiac sodium channel NaV 1.5. The phenotype is characterized by adrenaline-triggered ventricular arrhythmias. Electrophysiological properties and clinical manifestations are different from long-QT-3 or Brugada syndrome and might represent a distinct inherited arrhythmia syndrome.

Safety and effects of volume loading during transesophageal echocardiography in the pre-procedural work-up for left atrial appendage closure.

BACKGROUND: In patients undergoing left atrial appendage (LAA) closure, an accurate sizing of the LAA is key to optimize device sizing, procedural success and reduce complications. Previous studies have shown that intraprocedural volume loading increases LAA dimensions and improves device sizing. However, the safety and effects on LAA and device sizing of administering a fluid bolus during pre-procedural transesophageal echocardiography (TEE) are unknown. The aim of this study was to determine the safety and impact on LAA dimensions and device sizing of an intravenous (IV) fluid bolus administered during TEE in the setting of the pre-procedural work-up for LAA closure. METHODS: The study included a total of 72 patients who underwent TEE to assess suitability for LAAC and received a 500 ml IV bolus of normal saline. The LAA landing zone (LZ) and depth were measured by TEE before and after volume loading, and these measurements were used to predict the device size implanted during a subsequent percutaneous LAAC procedure. RESULTS: There were no complications associated with volume loading. The baseline mean LZ was 19.6 ± 3.6 mm at 90o, and 20.2 ± 4.1 mm at 135o. Following fluid bolus, the maximum diameter increased 1.5 ± 1.0 mm at 90o (p<0.001), and 1.3 ± 1.0 mm at 135o (p<0.001). The baseline mean depth of the LAA was 26.5 ± 5.5 mm at 90o, and 23.9 ± 5.8 mm at 135o. After fluid bolus, the mean depth increased by 1.5 ± 1.8 mm (p<0.001) and 1.6 ± 2.0 (p<0.001), at 90o and 135o, respectively. Sizing based on post-bolus measurements of the LZ significantly improved the agreement with the final device size selection during the procedure in 71.0% of cases (vs. 42.0% with pre-bolus measurements). CONCLUSIONS: Volume loading during ambulatory TEE as part of the pre-procedural work-up of LAAC is safe and significantly increases LAA dimensions. This strategy may become the new standard, particularly in centers performing LAAC with no TEE guidance, as it improves LAA sizing and more accurately predicts the final device size.

Cryoballoon or Radiofrequency Ablation for Atrial Fibrillation Assessed by Continuous Monitoring: A Randomized Clinical Trial.

BACKGROUND: Advanced generation ablation technologies have been developed to achieve more effective pulmonary vein isolation (PVI) and minimize arrhythmia recurrence after atrial fibrillation (AF) ablation. METHODS: We randomly assigned 346 patients with drug-refractory paroxysmal AF to contact force-guided radiofrequency ablation (CF-RF; n=115), 4-minute cryoballoon ablation (Cryo-4; n=115), or 2-minute cryoballoon ablation (Cryo-2; n=116). Follow-up was 12 months. The primary outcome was time to first documented recurrence of symptomatic or asymptomatic atrial tachyarrhythmia (AF, atrial flutter, or atrial tachycardia) between days 91 and 365 after ablation or a repeat ablation procedure at any time. Secondary end points included freedom from symptomatic arrhythmia and AF burden. All patients received an implantable loop recorder. RESULTS: One-year freedom from atrial tachyarrhythmia defined by continuous rhythm monitoring was 53.9%, 52.2%, and 51.7% with CF-RF, Cryo-4, and Cryo-2, respectively (P=0.87). One-year freedom from symptomatic atrial tachyarrhythmia defined by continuous rhythm monitoring was 79.1%, 78.2%, and 73.3% with CF-RF, Cryo-4, and Cryo-2, respectively (P=0.26). Compared with the monitoring period before ablation, AF burden was reduced by a median of 99.3% (interquartile range, 67.8%-100.0%) with CF-RF, 99.9% (interquartile range, 65.3%-100.0%) with Cryo-4, and 98.4% (interquartile range, 56.2%-100.0%) with Cryo-2 (P=0.36). Serious adverse events occurred in 3 patients (2.6%) in the CF-RF group, 6 patients (5.3%) in the Cryo-4 group, and 7 patients (6.0%) in the Cryo-2 group, with no significant difference between groups (P=0.24). The CF-RF group had a significantly longer procedure duration but significantly shorter fluoroscopy exposure (P<0.001 vs cryoballoon groups). CONCLUSIONS: In this multicenter, randomized, single-blinded trial, CF-RF and 2 different regimens of cryoballoon ablation resulted in no difference in 1-year efficacy, which was 53% by time to first recurrence but >98% burden reduction as assessed by continuous cardiac rhythm monitoring. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01913522.

Transesophageal echocardiography complications associated with interventional cardiology procedures.

BACKGROUND: Although there have been several reports documenting complications related with transesophageal echocardiography (TEE) manipulation following cardiac surgery, there is a paucity of data regarding the safety of TEE used to guide catheter-based interventions. The aim of this study was to determine the prevalence, types and risk factors of complications associated with procedures requiring active TEE guidance. METHODS: This study included 1249 consecutive patients undergoing either transcatheter aortic valve implantation (TAVI), Mitraclip, left atrial appendage occlusion (LAAO) or paravalvular leak closure (PVLC). Patients were divided into 2 cohorts based on the degree of probe manipulation required to guide the procedure and the risk of developing a TEE-related complication: low-risk (TAVI, n = 1037) and high-risk (Mitraclip, LAAO and PVLC, n = 212). Patients were further analyzed according to the occurrence of major and minor TEE-related complications. RESULTS: The overall incidence of TEE-related complications was 0.9% in the TAVI group and 6.1% in the rest of the cohort (P < .001). Patients in the high-risk cohort had also a higher incidence of major-complications (2.8% vs 0.6%, P = .008), and factors associated with an increased risk were being underweight, having a prior history of gastrointestinal bleeding and the use of chronic steroids/immunosuppressive medications. Procedural time under TEE-manipulation was longer in patients exhibiting complications and was an independent predictor of major complications (OR = 1.13, 95% CI 1.01-1.25, for each 10 minutes increments in imaging time). Patients with major complications undergoing Mitraclip had the longest median time under TEE-manipulation (297 minutes) and a risk of developing a major-complication that was 10.64 times higher than the rest of the cohort (95% CI 3.30-34.29, P < .001). CONCLUSION: The prevalence of TEE-related complications associated with interventional procedures is higher than previously reported. Undergoing a prolonged procedure, particularly in the setting of Mitraclip, was the main factor linked to TEE-related complications.

Impact of Left Common Pulmonary Veins in the Contact-Force vs. Cryoballoon Atrial Fibrillation Ablation (CIRCA-DOSE) Study.

BACKGROUND: Concerns remain regarding the effectiveness of PVI using the fixed diameter non-compliant cryoballoon in the presence of a left common pulmonary vein (LCPV). We sought to evaluate the effectiveness of PVI performed by contact-force guided radiofrequency (CF-RF) versus second-generation cryoballoon-based ablation in patients with LCPV. METHODS AND RESULTS: We enrolled 346 patients with paroxysmal AF and randomized them to CF-RF or cryoballoon ablation. PV anatomy was not assessed prior to enrolment, and there were no exclusions based on PV anatomy. All patients received an implantable cardiac monitor. LCPV was observed in 13.6% of patients (47/346). Left atrial time and fluoroscopy time did not differ between those with and without LCPV (P=0.58 and P=0.06, respectively). Freedom from any atrial tachyarrhythmia at one year was observed in 46.8% with LCPV and 54.5% without LCPV (P=0.06). In those with LCPV the freedom from any atrial tachyarrhythmia did not differ between those randomized to CF-RF or cryoballoon ablation (HR for recurrence 1.19, 95% CI 0.53-2.65, P=0.69). In those with LCPV the AF burden was reduced to a similar extent with CF-RF and cryoballoon ablation (99.7% vs. 99.5%, respectively; P=0.97). CONCLUSIONS: In this randomized clinical trial, the presence of a LCPV was associated with a trend towards higher rates of arrhythmia recurrence following PVI. No significant difference in arrhythmia recurrence was observed between patients with LCPV randomized to cryoballoon ablation or contact-force guided RF ablation, suggesting that either ablation modality is suitable in this population. (Cryoballoon vs. Irrigated Radiofrequency Catheter Ablation [CIRCA-DOSE], NCT01913522) This article is protected by copyright. All rights reserved.

Findings of remote monitoring of implantable cardioverter defibrillators during the COVID-19 pandemic.

BACKGROUND: Monitoring of cardiac implantable electronic devices was highly impacted by the COVID-19 pandemic considering the high volume of in-person visits for regular follow-up. Recent recommendations highlight the important role of remote monitoring to prevent exposure to the virus. This study compared remote monitoring of implantable cardioverter defibrillators (ICDs) in patients whose in-person annual visit was substituted for a remote monitoring session with patients who were already scheduled for a remote monitoring session. METHODS: This was a cross-sectional observational study of 329 consecutive patients between 20 March and 24 April 2020. Group 1 included 131 patients whose in-person annual visit was substituted for a remote monitoring session. Group 2 included 198 patients who underwent a remote monitoring session as scheduled in their usual device follow-up. The time interval since the last in-person visit was 13.3 ± 3.2 months in group 1 and 5.9 ± 1.7 months in group 2 (P < .01). RESULTS: In group 1, 15 patients (11.5%) experienced a clinical event compared to 15 patients (7.6%) in group 2 (P = .25). Nineteen patients (14.5%) required a physician intervention in group 1 compared to 19 patients (9.6%) in group 2 (P = .22). Two patients (1.5%) in group 1 and four patients (2.0%) in group 2 required an early in-person follow-up visit during the pandemic (P > .99). CONCLUSION: Remote monitoring of ICDs is useful to identify clinical events and allows physicians to treat patients appropriately during the COVID-19 pandemic regardless of the time interval since their last in-person visit. It reduces significantly in-person visit for regular follow-up.

Orthodromic atrioventricular reentrant tachycardia using a concealed isoproterenol-sensitive accessory pathway.

Accessory pathways (APs) represent the substrate for atrioventricular reentrant tachycardia. Catecholamine-sensitivity is an uncommon feature of APs and has been almost exclusively been described in APs with antegrade conduction. We present the rare case of a catecholamine-dependent concealed AP that was only unmasked upon isoproterenol stimulation and successfully ablated. This case highlights the importance of systematic isoproterenol stimulation in patients referred for ablation of supraventricular tachycardia - in particular if the baseline electrophysiology study is negative. Otherwise, ablation targets may be missed. LEARNING OBJECTIVE: The absence of retrograde ventriculo-atrial conduction does not automatically exclude the presence of a concealed accessory pathway. Systematic isoproterenol stimulation should be part of any electrophysiology study for supraventricular tachycardia, to search for catecholamine-sensitive accessory pathways that may be otherwise missed.

Time-to-first appropriate shock in patients implanted prophylactically with an implantable cardioverter-defibrillator: data from the Survey on Arrhythmic Events in BRUgada Syndrome (SABRUS).

AIMS: Data on predictors of time-to-first appropriate implantable cardioverter-defibrillator (ICD) therapy in patients with Brugada Syndrome (BrS) and prophylactically implanted ICD's are scarce. METHODS AND RESULTS: SABRUS (Survey on Arrhythmic Events in BRUgada Syndrome) is an international survey on 678 BrS patients who experienced arrhythmic event (AE) including 252 patients in whom AE occurred after prophylactic ICD implantation. Analysis was performed on time-to-first appropriate ICD discharge regarding patients' characteristics. Multivariate logistic regression models were utilized to identify which parameters predicted time to arrhythmia ≤5 years. The median time-to-first appropriate ICD therapy was 24.8 ± 2.8 months. A shorter time was observed in patients from Asian ethnicity (P < 0.05), those with syncope (P = 0.001), and those with Class IIa indication for ICD (P = 0.001). A longer time was associated with a positive family history of sudden cardiac death (P < 0.05). Multivariate Cox regression revealed shorter time-to-ICD therapy in patients with syncope [odds ratio (OR) 1.65, P = 0.001]. In 193 patients (76.6%), therapy was delivered during the first 5 years. Factors associated with this time were syncope (OR 0.36, P = 0.001), spontaneous Type 1 Brugada electrocardiogram (ECG) (OR 0.5, P < 0.05), and Class IIa indication (OR 0.38, P < 0.01) as opposed to Class IIb (OR 2.41, P < 0.01). A near-significant trend for female gender was also noted (OR 0.13, P = 0.052). Two score models for prediction of <5 years to shock were built. CONCLUSION: First appropriate therapy in BrS patients with prophylactic ICD's occurred during the first 5 years in 76.6% of patients. Syncope and spontaneous Type 1 Brugada ECG correlated with a shorter time to ICD therapy.

Validation of a novel single lead ambulatory ECG monitor - Cardiostat™ - Compared to a standard ECG Holter monitoring.

BACKGROUND: Cardiostat™ is a single lead ambulatory ECG monitor. Recording is made through 2 electrodes positioned in a lead 1-like configuration. We first validated its accuracy for atrial fibrillation detection compared to a 12-lead ECG. In the second phase of the study, arrhythmia detection accuracy was compared between Cardiostat™ ambulatory ECG and a standard 24 h Holter ECG monitoring. METHOD/RESULTS: Phase one of the study included patients undergoing cardioversion for atrial fibrillation (AF) or atrial flutter. Cardiostat™ tracings were compared with standard 12-lead ECG. In the second phase, patients undergoing 24 h ambulatory Holter ECG monitoring for control or suspicion of atrial fibrillation (AF) were included. Simultaneous Holter monitoring and Cardiostat™ ECG recordings were performed. Tracings were analysed and compared. Two hundred twelve monitoring were compared. AF was diagnosed in 73 patients. Agreement between Cardiostat™ ECG and standard Holter monitoring was 99% for AF detection with kappa = 0.99. Kappa correlation for atrial flutter detection was only moderate at 0.51. AF burden was similar in both recordings. Noise hindered analysis in a greater proportion with Cardiostat™ compared to Holter ambulatory ECG (8.5 vs 3.8%). CONCLUSION: Cardiostat™ ambulatory ECG device showed excellent correlation with the standard Holter ECG monitoring for AF detection. Holter monitoring was however superior to discriminate premature atrial and ventricular beats and to qualify the morphology of PVCs since it has more vectors for analysis. Added value of Cardiostat™ includes longer monitoring duration, less cumbersome installation and water resistance.

A randomized clinical trial of early invasive intervention for atrial fibrillation (EARLY-AF) - methods and rationale.

BACKGROUND: The ideal management of patients with newly diagnosed symptomatic atrial fibrillation (AF) remains unknown. Current practice guidelines recommend a trial of antiarrhythmic drugs (AAD) prior to considering an invasive ablation procedure. However, earlier ablation offers an opportunity to halt the progressive patho-anatomical changes associated with AF, as well as impart other important clinical benefits. OBJECTIVE: The aim of this study is to determine the optimal initial management strategy for patients with newly diagnosed, symptomatic atrial fibrillation. METHODS/DESIGN: The EARLY-AF study (ClinicalTrials.govNCT02825979) is a prospective, open label, multicenter, randomized trial with a blinded assessment of outcomes. A total of 298 patients will be randomized in a 1:1 fashion to first-line AAD therapy, or first-line cryoballoon-based pulmonary vein isolation. Patients with symptomatic treatment naïve AF will be included. Arrhythmia outcomes will be assessed by implantable cardiac monitor (ICM). The primary outcome is time to first recurrence of AF, atrial flutter, or atrial tachycardia (AF/AFL/AT) between days 91 and 365 following AAD initiation or AF ablation. Secondary outcomes include arrhythmia burden, quality of life, and healthcare utilization. DISCUSSION: The EARLY-AF study is a randomized trial designed to evaluate the optimal first management approach for patients with AF. We hypothesize that catheter ablation will be superior to drug therapy in prevention of AF recurrence.

The Optimal Anti-Coagulation for Enhanced-Risk Patients Post-Catheter Ablation for Atrial Fibrillation (OCEAN) trial.

BACKGROUND: The optimal long-term antithrombotic regimen for patients after successful catheter-based atrial fibrillation (AF) ablation is not well defined. Presently, practice variation exists, and the benefits of oral anticoagulation over antiplatelet therapy across the entire spectrum of stroke risk profile remain undefined in the postablation population. To date, there are no randomized trials to inform clinicians on this therapeutic question. OBJECTIVE: The objective was to assess whether rivaroxaban is superior to acetylsalicylic acid (ASA) in reducing the risk of clinically overt stroke, systemic embolism, or covert stroke among patients without apparent recurrent atrial arrhythmias for at least 1 year after their most recent AF ablation procedure. METHODS/DESIGN: A prospective, multicenter, open-label, randomized trial with blinded assessment of outcomes is under way (NCT02168829). Atrial fibrillation patients with at least 1 stroke risk factor (as defined by the CHA2DS2-VASc score) and without known atrial arrhythmia recurrences for at least 12 months after ablation are randomized to rivaroxaban 15 mg or ASA 75-160 mg daily. The primary outcome is a composite of clinically overt stroke, systemic embolism, and covert stroke based on brain magnetic resonance imaging. Key secondary outcomes include major bleeding outcomes, intracranial hemorrhage, transient ischemic attack, neuropsychological testing, quality of life, and an economic analysis. Subjects will be followed for 3 years. The estimated overall sample size is 1,572 subjects (786 per arm). DISCUSSION: The OCEAN trial is a multicenter randomized controlled trial evaluating 2 antithrombotic treatment strategies for patients with risk factors for stroke after apparently successful AF ablation. We hypothesize that rivaroxaban will reduce the occurrence of clinically overt stroke, systemic embolism, and covert stroke when compared with ASA alone.