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.

Randomized Ablation-Based Rhythm-Control Versus Rate-Control Trial in Patients With Heart Failure and Atrial Fibrillation: Results from the RAFT-AF trial.

BACKGROUND: Atrial fibrillation (AF) and heart failure (HF) frequently coexist and can be challenging to treat. Pharmacologically based rhythm control of AF has not proven to be superior to rate control. Ablation-based rhythm control was compared with rate control to evaluate if clinical outcomes in patients with HF and AF could be improved. METHODS: This was a multicenter, open-label trial with blinded outcome evaluation using a central adjudication committee. Patients with high-burden paroxysmal (>4 episodes in 6 months) or persistent (duration <3 years) AF, New York Heart Association class II to III HF, and elevated NT-proBNP (N-terminal pro brain natriuretic peptide) were randomly assigned to ablation-based rhythm control or rate control. The primary outcome was a composite of all-cause mortality and all HF events, with a minimum follow-up of 2 years. Secondary outcomes included left ventricular ejection fraction, 6-minute walk test, and NT-proBNP. Quality of life was measured using the Minnesota Living With Heart Failure Questionnaire and the AF Effect on Quality of Life. The primary analysis was time-to-event using Cox proportional hazards modeling. The trial was stopped early because of a determination of apparent futility by the Data Safety Monitoring Committee. RESULTS: From December 1, 2011, to January 20, 2018, 411 patients were randomly assigned to ablation-based rhythm control (n=214) or rate control (n=197). The primary outcome occurred in 50 (23.4%) patients in the ablation-based rhythm-control group and 64 (32.5%) patients in the rate-control group (hazard ratio, 0.71 [95% CI, 0.49-1.03]; P=0.066). Left ventricular ejection fraction increased in the ablation-based group (10.1±1.2% versus 3.8±1.2%, P=0.017), 6-minute walk distance improved (44.9±9.1 m versus 27.5±9.7 m, P=0.025), and NT-proBNP demonstrated a decrease (mean change -77.1% versus -39.2%, P<0.0001). Minnesota Living With Heart Failure Questionnaire demonstrated greater improvement in the ablation-based rhythm-control group (least-squares mean difference of -5.4 [95% CI, -10.5 to -0.3]; P=0.0036), as did the AF Effect on Quality of Life score (least-squares mean difference of 6.2 [95% CI, 1.7-10.7]; P=0.0005). Serious adverse events were observed in 50% of patients in both treatment groups. CONCLUSIONS: In patients with high-burden AF and HF, there was no statistical difference in all-cause mortality or HF events with ablation-based rhythm control versus rate control; however, there was a nonsignificant trend for improved outcomes with ablation-based rhythm control over rate control. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT01420393.

Efficacy and safety of supraclavicular and pectoralis nerve blocks as primary peri-procedural analgesia for cardiac electronic device implantation: A pilot study.

BACKGROUND: Cardiac implantable electronic devices (CIEDs) are routinely implanted using intravenous drugs for sedation. However, some patients are poor candidates for intravenous sedation. OBJECTIVE: We present a case series demonstrating the safety and efficacy of a novel, ultrasound-guided nerve block technique that allows for pre-pectoral CIED implantation. The targets are the supraclavicular nerve (SCN) and pectoral nerve (PECS1). METHODS: We enrolled 20 patients who were planned for new CIED implantation. Following US-localization of the SCN and PECS1, local anesthetic (LA) was instilled at least 30-60 min pre-procedure. Successful nerve block was determined if < 5 mL of intraprocedural LA was used, along with lack of sensation with skin and deep tissue pinprick. Optional sedation was offered to patients' pre-procedure if discomfort was reported. RESULTS: Seventeen patients (85%) had a successful periprocedural nerve block, with only three patients exceeding 5 mL of LA. SCN and PECS1 success occurred in 19 (95%) and 18 (90%) patients, respectively. The overall success of nerve block by fulfilling all the criteria was demonstrated in 17 out of 20 patients (85%). Patients who reported no pain (VAS score = 0) were distributed as follows: 13 patients (65%) in the immediate post-procedure interval, 18 patients (90%) at the 1 h post-implant interval, and 14 patients (70%) at the 24 h post- implant interval. The median cumulative VAS score was 0 (IQR = 0 - 1). There were no reported significant adverse effects. CONCLUSION: SCN and PECS1 nerve blocks are safe and effective for patients undergoing CIED implantation to minimize or eliminate the use of intravenous sedation.

An International Multicenter Evaluation of Type 5 Long QT Syndrome: A Low Penetrant Primary Arrhythmic Condition.

BACKGROUND: Insight into type 5 long QT syndrome (LQT5) has been limited to case reports and small family series. Improved understanding of the clinical phenotype and genetic features associated with rare KCNE1 variants implicated in LQT5 was sought through an international multicenter collaboration. METHODS: Patients with either presumed autosomal dominant LQT5 (N = 229) or the recessive Type 2 Jervell and Lange-Nielsen syndrome (N = 19) were enrolled from 22 genetic arrhythmia clinics and 4 registries from 9 countries. KCNE1 variants were evaluated for ECG penetrance (defined as QTc >460 ms on presenting ECG) and genotype-phenotype segregation. Multivariable Cox regression was used to compare the associations between clinical and genetic variables with a composite primary outcome of definite arrhythmic events, including appropriate implantable cardioverter-defibrillator shocks, aborted cardiac arrest, and sudden cardiac death. RESULTS: A total of 32 distinct KCNE1 rare variants were identified in 89 probands and 140 genotype positive family members with presumed LQT5 and an additional 19 Type 2 Jervell and Lange-Nielsen syndrome patients. Among presumed LQT5 patients, the mean QTc on presenting ECG was significantly longer in probands (476.9±38.6 ms) compared with genotype positive family members (441.8±30.9 ms, P<0.001). ECG penetrance for heterozygous genotype positive family members was 20.7% (29/140). A definite arrhythmic event was experienced in 16.9% (15/89) of heterozygous probands in comparison with 1.4% (2/140) of family members (adjusted hazard ratio [HR] 11.6 [95% CI, 2.6-52.2]; P=0.001). Event incidence did not differ significantly for Type 2 Jervell and Lange-Nielsen syndrome patients relative to the overall heterozygous cohort (10.5% [2/19]; HR 1.7 [95% CI, 0.3-10.8], P=0.590). The cumulative prevalence of the 32 KCNE1 variants in the Genome Aggregation Database, which is a human database of exome and genome sequencing data from now over 140 000 individuals, was 238-fold greater than the anticipated prevalence of all LQT5 combined (0.238% vs 0.001%). CONCLUSIONS: The present study suggests that putative/confirmed loss-of-function KCNE1 variants predispose to QT prolongation, however, the low ECG penetrance observed suggests they do not manifest clinically in the majority of individuals, aligning with the mild phenotype observed for Type 2 Jervell and Lange-Nielsen syndrome patients.

Enrichment of loss-of-function and copy number variants in ventricular cardiomyopathy genes in 'lone' atrial fibrillation.

AIMS: Atrial fibrillation (AF) is a complex heritable disease whose genetic underpinnings remain largely unexplained, though recent work has suggested that the arrhythmia may develop secondary to an underlying atrial cardiomyopathy. We sought to evaluate for enrichment of loss-of-function (LOF) and copy number variants (CNVs) in genes implicated in ventricular cardiomyopathy in 'lone' AF. METHODS AND RESULTS: Whole-exome sequencing was performed in 255 early onset 'lone' AF cases, defined as arrhythmia onset prior to 60 years of age in the absence of known clinical risk factors. Subsequent evaluations were restricted to 195 cases of European genetic ancestry, as defined by principal component analysis, and focused on a pre-defined set of 43 genes previously implicated in ventricular cardiomyopathy. Bioinformatic analysis identified 6 LOF variants (3.1%), including 3 within the TTN gene, among cases in comparison with 4 of 503 (0.80%) controls [odds ratio: 3.96; 95% confidence interval (CI): 1.11-14.2; P = 0.033]. Further, two AF cases possessed a novel heterozygous 8521 base pair TTN deletion, confirmed with Sanger sequencing and breakpoint validation, which was absent from 4958 controls (P = 0.0014). Subsequent cascade screening in two families revealed evidence of co-segregation of a LOF variant with 'lone' AF. CONCLUSION: 'Lone' AF cases are enriched in rare LOF variants from cardiomyopathy genes, findings primarily driven by TTN, and a novel TTN deletion, providing additional evidence to implicate atrial cardiomyopathy as an AF genetic sub-phenotype. Our results also highlight that AF may develop in the context of these variants in the absence of a discernable ventricular cardiomyopathy.

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.

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.

A simple maneuver to determine if septal accessory pathway ablation requires a left atrial approach.

INTRODUCTION: Septal accessory pathway (AP) ablation can be challenging due to the complex anatomy of the septal region. The decision to access the left atrium (LA) is often made after failure of ablation from the right. We sought to establish whether the difference between ventriculo-atrial (VA) time during right ventricular (RV) apical pacing versus the VA during tachycardia would help establish the successful site for ablation of septal APs. METHODS: Intracardiac electrograms of patients with orthodromic reciprocating tachycardia (ORT) using a septal AP with successful catheter ablation were reviewed. The ∆VA was the difference between the VA interval during RV apical pacing and the VA interval during ORT. The difference in the VA interval during right ventricular entrainment and ORT (StimA-VA) was also measured. RESULTS: The median ∆VA time was significantly less in patients with a septal AP ablated on the right side compared with patients with a septal AP ablated on the left side (12 ± 19 vs. 56 ± 10 ms, p < .001). The StimA-VA was significantly different between the two groups (22 ± 14 vs. 53 ± 9 ms, p < .001). The ∆VA and StimA-VA were always ≤ 40 ms in patients with non-decremental septal APs ablated from the right side and always greater than 40 ms in those with septal APs ablated from the left. CONCLUSION: ΔVA and StimA-VA values identified with RV apical pacing in the setting of ORT involving a septal AP predict when left atrial access will be necessary for successful ablation.

Relationship between quality of life and burden of recurrent atrial fibrillation following ablation: CAPCOST multicentre cohort study.

AIMS: Atrial fibrillation (AF) significantly impairs patients' quality of life (QOL). We performed this study to investigate the effect of AF-ablation success and atrial fibrillation burden (AFB) on QOL measures. METHODS AND RESULTS: Overall, 230 patients with paroxysmal AF refractory to antiarrhythmic drugs were enrolled and underwent ablation in a multicentre, prospective cohort. Electrocardiogram, 48-h Holter, Canadian Cardiovascular Society Severity of Atrial Fibrillation (CCS-SAF), short form-12 (SF-12), and Atrial Fibrillation Effect on Quality of life (AFEQT) scales were used to assess patients. Atrial fibrillation burden was defined as total duration of AF during the month prior to each visit (h/month). The change in AFB was calculated as the difference between the month prior to the 12-month post-ablation and the baseline pre-ablation. The Minimal Clinically Important Difference (MCID) was considered as a 19-point change for AFEQT and 3-5-point change for SF-12 scores. There was significant rise in the AFEQT and SF12 and decrease in CCS-SAF score post-AF ablation; however, the magnitude of these changes was greater in patients without AF recurrence (P < 0.05). The QOL score that best differentiated patients with and without recurrence was AFEQT, while, CCS-SAF was the most specific score. Patients with AFB decrease >19 h/month had significantly greater change in QOL scores. Atrial fibrillation burden < 24 h/month at 12-months post-ablation was associated with significant changes in QOL and CCS-SAF when adjusting for baseline scores and other covariates. These changes were consistent with the MCID of these measures. CONCLUSION: Patients experience significant improvements in QOL post-ablation, which correlate with a decrease in AFB despite ongoing brief recurrences of AF. CLINICAL TRIAL REGISTRATION: NCT01562912. https://www.clinicaltrials.gov/ct2/show/NCT01562912? term=capcost&rank=1.

Ventricular Tachycardia Ablation versus Escalation of Antiarrhythmic Drugs.

BACKGROUND: Recurrent ventricular tachycardia among survivors of myocardial infarction with an implantable cardioverter-defibrillator (ICD) is frequent despite antiarrhythmic drug therapy. The most effective approach to management of this problem is uncertain. METHODS: We conducted a multicenter, randomized, controlled trial involving patients with ischemic cardiomyopathy and an ICD who had ventricular tachycardia despite the use of antiarrhythmic drugs. Patients were randomly assigned to receive either catheter ablation (ablation group) with continuation of baseline antiarrhythmic medications or escalated antiarrhythmic drug therapy (escalated-therapy group). In the escalated-therapy group, amiodarone was initiated if another agent had been used previously. The dose of amiodarone was increased if it had been less than 300 mg per day or mexiletine was added if the dose was already at least 300 mg per day. The primary outcome was a composite of death, three or more documented episodes of ventricular tachycardia within 24 hours (ventricular tachycardia storm), or appropriate ICD shock. RESULTS: Of the 259 patients who were enrolled, 132 were assigned to the ablation group and 127 to the escalated-therapy group. During a mean (±SD) of 27.9±17.1 months of follow-up, the primary outcome occurred in 59.1% of patients in the ablation group and 68.5% of those in the escalated-therapy group (hazard ratio in the ablation group, 0.72; 95% confidence interval, 0.53 to 0.98; P=0.04). There was no significant between-group difference in mortality. There were two cardiac perforations and three cases of major bleeding in the ablation group and two deaths from pulmonary toxic effects and one from hepatic dysfunction in the escalated-therapy group. CONCLUSIONS: In patients with ischemic cardiomyopathy and an ICD who had ventricular tachycardia despite antiarrhythmic drug therapy, there was a significantly lower rate of the composite primary outcome of death, ventricular tachycardia storm, or appropriate ICD shock among patients undergoing catheter ablation than among those receiving an escalation in antiarrhythmic drug therapy. (Funded by the Canadian Institutes of Health Research and others; VANISH ClinicalTrials.gov number, NCT00905853.).

Comparison of efficacy of phased multipolar versus traditional radiofrequency ablation: A prospective, multicenter study (CAPCOST).

BACKGROUND: Multipolar phased pulmonary vein ablation catheter (PVAC), specifically its second-generation (PVAC-Gold), has been associated with reduced procedural time for atrial fibrillation (AF) ablation compared to traditional catheters. We performed this study to compare the efficacy of PVAC with point-by-point radiofrequency (RF) ablation. METHODS: This is a multicenter-cohort study (2012-2017), involving patients with symptomatic, paroxysmal AF refractory to at least one antiarrhythmic medication. Overall, 230 patients were enrolled to (A) PVAC and (B) control groups. Subanalyses were done for ablations performed with PVAC-Gold, and for ablations performed without left atrial (LA) ablation in addition to pulmonary vein isolation. Electrocardiogram and 48-h Holter monitoring were used to assess patients at 3, 6, 9, and 12 months postablation. Recurrence was defined as any atrial arrhythmia >30 s excluding an initial 3-month blanking period. RESULTS: Freedom from any atrial arrhythmia at 12 months postablation was 35.70% and 52.80% in groups A and B, respectively (P = .01). Freedom from atrial arrhythmia was not significantly different when limiting the PVAC cohort to PVAC-Gold and excluding patients with additional LA ablation (A: 44.30%; B: 44.30%, P = .80). Procedural and ablation time was significantly lower in group A than B. Multivariate regression model showed female gender (odds ratio [OR] = 2.90) and recurrence during blanking period (OR = 6.60) as significant predictors of recurrence. CONCLUSION: This study suggests that PVAC may achieve less freedom from AF than point-by-point RF; however, efficacy is similar when comparing PVAC-Gold and point-by-point stand-alone PV isolation. PVAC is associated with significantly reduced procedural times for AF ablation.

Subclinical Atrial Fibrillation in Older Patients.

BACKGROUND: Long-term continuous electrocardiographic monitoring shows a substantial prevalence of asymptomatic, subclinical atrial fibrillation (SCAF) in patients with pacemakers and patients with cryptogenic stroke. Whether SCAF is also common in other patients without these conditions is unknown. METHODS: We implanted subcutaneous electrocardiographic monitors (St. Jude CONFIRM-AF) in patients ≥65 years of age attending cardiovascular or neurology outpatient clinics if they had no history of atrial fibrillation but had any of the following: CHA2DS2-VASc score of ≥2, sleep apnea, or body mass index >30 kg/m2. Eligibility also required either left atrial enlargement (≥4.4 cm or volume ≥58 mL) or increased (≥290 pg/mL) serum NT-proBNP (N-terminal pro-B-type natriuretic peptide). Patients were monitored for SCAF lasting ≥5 minutes. RESULTS: Two hundred fifty-six patients were followed up for 16.3±3.8 months. Baseline age was 74±6 years; mean CHA2DS2-VASc score was 4.1±1.4; left atrial diameter averaged 4.7±0.8 cm; and 48% had a prior stroke, transient ischemic attack, or systemic embolism. SCAF ≥5 minutes was detected in 90 patients (detection rate, 34.4%/y; 95% confidence interval [CI], 27.7-42.3). Baseline predictors of SCAF were increased age (hazard ratio [HR] per decade, 1.55; 95% CI, 1.11-2.15), left atrial dimension (HR per centimeter diameter, 1.43; 95% CI, 1.09-1.86), and blood pressure (HR per 10 mm Hg, 0.87; 95% CI, 0.78-0.98), but not prior stroke. The rate of occurrence of SCAF in those with a history of stroke, systemic embolism, or transient ischemic attack was 39.4%/y versus 30.3%/y without (P=0.32). The cumulative SCAF detection rate was higher (51.9%/y) in those with left atrial volume above the median value of 73.5 mL. CONCLUSIONS: SCAF is frequently detected by continuous electrocardiographic monitoring in older patients without a history of atrial fibrillation who are attending outpatient cardiology and neurology clinics. Its clinical significance is unclear. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01694394.

Mexiletine or catheter ablation after amiodarone failure in the VANISH trial.

INTRODUCTION: In patients with ischemic heart disease and ventricular tachycardia (VT) refractory to high dose amiodarone, the two most common therapeutic options are adjunctive mexiletine therapy or catheter ablation. There are little existing data on the efficacy of these strategies. We examined the relative efficacy of adjunctive mexiletine and catheter ablation among patients enrolled in the VANISH trial. METHODS: All subjects enrolled in the VANISH trial who had VT refractory to high dose (≥ 300 mg daily) amiodarone at baseline were included. Per protocol, subjects randomized to escalated drug therapy received adjunctive mexiletine. RESULTS: Nineteen of the 259 patients were receiving high-dose amiodarone at baseline and 11 were randomized to escalated therapy with mexiletine and 8 to ablation. The adjunctive mexiletine group had a higher rate of the primary composite outcome (death, VT storm, or appropriate shock) in comparison to catheter ablation (HR 6.87 [2.08-22.8]). Over 90% of the patients in the adjunctive mexiletine/group experienced a primary endpoint during a median 9.2 months' follow-up. There was no difference in the rate of adverse events between the two groups. CONCLUSIONS: Mexiletine has limited efficacy in the treatment of recurrent VT despite high-dose amiodarone therapy, in patients with ischemic heart disease. Catheter ablation is a superior strategy in this population.

Quality of life with ablation or medical therapy for ventricular arrhythmias: A substudy of VANISH.

BACKGROUND/OBJECTIVE: We compared health-related quality of life (HRQoL) in patients randomized to escalated therapy and those randomized to ablation for ventricular tachycardia in the VANISH trial. METHODS: HRQoL was assessed among VANISH patients at baseline and 3-, 6-, and 12-month follow-up visits. Four validated instruments were used: the SF-36, the implanted cardioverter defibrillator (ICD) Concerns questionnaire (ICDC), the Hospital Anxiety and Depression Scale (HADS), and the EuroQol five dimensions questionnaire (EQ-5D). Linear mixed-effects modeling was used for repeated measures with SF-36, HADS, ICDC, and EQ-5D as dependent variables. In a second model, treatment was subdivided by amiodarone use prior to enrollment. RESULTS: HRQoL did not differ significantly between those randomized to ablation or escalated therapy. On subgroup analysis, improvement in SF-36 measures was seen at 6 months in the ablation group for social functioning (63.5-69.3, P = 0.03) and energy/fatigue (43.0-47.9, P = 0.01). ICDC measures showed a reduction in ICD concern in the ablation group at 6 months (10.4-8.7, P = 0.01) and a reduction in ICD concern in the escalated therapy group at 6 months (10.9-9.4, P = 0.04). EQ-5D measures showed a significant improvement in overall health in ablation patients at 6 months (63.4-67.3, P = 0.04). CONCLUSION: Patients in the VANISH study randomized to ablation did not have a significant change in quality of life outcomes compared to those randomized to escalated therapy. Some subgroup findings were significant, as those randomized to ablation showed persistent improvement in SF-36 energy/fatigue and ICD concern, and transient improvement in SF-36 social functioning and EQ-5D overall health.

Cost Effectiveness of Implantable Cardiac Monitor-Guided Intermittent Anticoagulation for Atrial Fibrillation: An Analysis of the REACT.COM Pilot Study.

INTRODUCTION: Anticoagulation guidelines for patients with atrial fibrillation (AF) disregard AF burden. A strategy of targeted anticoagulation with novel oral anticoagulants (NOACs) based on continuous rhythm assessment with an implantable cardiac monitor (ICM) has recently been explored. We evaluated the potential cost-effectiveness of this strategy versus projected outcomes with continuous anticoagulation. METHODS AND RESULTS: We developed a Markov model using data from the Rhythm Evaluation for AntiCoagulaTion With COntinuous Monitoring (REACT.COM) pilot study (N = 59) and prior NOAC trials to calculate the costs and quality-adjusted life years (QALYs) associated with ICM-guided intermittent anticoagulation for AF versus standard care during a 3-year time horizon. Health state utilities were estimated from the pilot study population using the SF-12. Costs were based on current Medicare reimbursement. Over 14 ± 4 months of follow-up, 18 of 59 patients had 35 AF episodes. The ICM-guided strategy resulted in a 94% reduction in anticoagulant use relative to continuous treatment. There were no strokes, 3 (5.1%) TIAs, 2 major bleeding events (on aspirin) and 3 minor bleeding events with the ICM-guided strategy. The projected total 3-year costs were $12,535 for the ICM-guided strategy versus $13,340 for continuous anticoagulation. Projected QALYs were 2.45 for both groups. CONCLUSION: Based on a pilot study, a strategy of ICM-guided anticoagulation with NOACs may be cost-saving relative to expected outcomes with continuous anticoagulation, with similar quality-adjusted survival. This strategy could be attractive from a health economic perspective if shown to be safe and effective in a rigorous clinical trial.

Targeted Anticoagulation for Atrial Fibrillation Guided by Continuous Rhythm Assessment With an Insertable Cardiac Monitor: The Rhythm Evaluation for Anticoagulation With Continuous Monitoring (REACT.COM) Pilot Study.

INTRODUCTION: Chronic anticoagulation is recommended for patients with AF and additional stroke risk factors, even during long periods of sinus rhythm. Continuous rhythm assessment with an insertable cardiac monitor (ICM) and use of rapid onset novel oral anticoagulants (NOACs) allow for targeted anticoagulation only around an AF episode, potentially reducing bleeding complications without compromising stroke risk. METHODS: This multicenter, single-arm study enrolled patients on NOAC with nonpermanent AF and CHADS2 score 1 or 2. After a 60-day run-in with no AF episodes ≥ 1 hour, NOACs were discontinued but reinitiated for 30 days following any AF episode ≥ 1 hour diagnosed through daily ICM transmissions. Major endpoints included time on NOAC, stroke, and bleeding. RESULTS: Among 59 enrollees, 75% were male, age 67 ± 8 years, 76% paroxysmal AF, 69% had prior AF ablation, and mean CHADS2 score 1.3 ± 0.5. Over 466 ± 131 mean days of follow-up there were 24,004 ICM transmissions with a compliance rate of 98.7%. A total of 35 AF episodes ≥ 1 hour occurred in 18 (31%) patients, resulting in a total time on NOAC of 1,472 days. This represents a 94% reduction in the time on NOAC compared to chronic anticoagulation. There were three traumatic bleeds (all on aspirin), three potential transient ischemic attacks (all on aspirin with CHADS2 score of 1), and no strokes or deaths. CONCLUSIONS: A targeted strategy of ICM-guided intermittent NOAC administration is feasible. A large-scale trial is necessary to evaluate the safety of this approach.

Pulmonary Vein Isolation With Incomplete Antral Ablation Lines: Is More Ablation Necessary? Results of a Randomized Trial.

BACKGROUND: A full circumferential set of antral lesions is not always required for bidirectional pulmonary vein conduction block. It is unknown whether a partial lesion set that isolates the veins will have clinical success rates similar to a full circumferential lesion set, and if procedural times or procedural risk will be affected. METHODS: We performed a prospective, randomized clinical trial to test the hypothesis that a partial lesion set that isolates the pulmonary veins has comparable clinical success rate and shorter procedure times compared to a strategy of completing the circumferential lesion set once the veins are isolated. RESULTS: A total of 119 patients were enrolled, 59 randomized to circumferential ablation, and 60 to segmental. Mean age was 58.3 ± 10.1, 77% male. Mean procedure time was 221.0 ± 46.9 minutes in circumferential and 224.7 ± 51.3 in segmental (P = 0.68). Twelve-month freedom from AF recurrence was 61.3% overall, 64.4% in circumferential, and 58.3% in segmental (P = 0.50). Among 25 segmental patients with AF recurrence, 23 underwent second ablation. Among 33 areas of conduction recovery, 23 (70%) occurred in segments ablated at first procedure and 10 (30%) in segments not previously ablated, suggesting reversible conduction block from edema. CONCLUSION: No difference in AF recurrence or procedure time is detectable in a sample of 119 patients randomized to segmental or circumferential antral ablation to achieve pulmonary vein isolation. Second ablation procedures confirmed that some antral sites do not require ablation. A segmental approach results in unacceptably high rates of untargeted or recovered antral sites to make this approach feasible.

Catheter ablation for atrial flutter: a survey by the European Heart Rhythm Association and Canadian Heart Rhythm Society.

The purpose of this EP wire survey was to examine current practice in the management of both cavotricuspid isthmus (CTI)-dependent and non-CTI-dependent atrial flutter (AFL) ablation amongst electrophysiologists in European and Canadian centres and to understand how current opinions vary from guidelines. The results of the survey were collected from a detailed questionnaire that was created by the European Heart Rhythm Association Research Network and the Canadian Heart Rhythm Society. Responses were received from 89 centres in 12 countries. The survey highlighted variability within certain aspects of the management of AFL ablation. The variability in opinion regarding other procedural details suggests a need for further research in this area and consideration of the development of guidelines specific to AFL. Overall, there is reasonable consensus regarding oral anticoagulation and the desired endpoints of ablation for patients with CTI-dependent AFL and for non-CTI-dependent AFL.

Atrial fibrillation and heart failure: a bad combination.

PURPOSE OF REVIEW: Heart failure and atrial fibrillation are both common cardiac conditions that share multiple risk factors. Heart failure is a risk for atrial fibrillation and atrial fibrillation is a risk for heart failure. The need to understand the interplay between these two cardiac conditions and the effectiveness of management options becomes increasingly relevant. RECENT FINDINGS: Recent studies have focused on the prognostic nature of atrial fibrillation and heart failure, the questionable utility of digoxin and beta-blocker therapy when heart failure and atrial fibrillation coexist, and the efficacy of cardiac ablation and resynchronization therapy with concomitant heart failure and atrial fibrillation. SUMMARY: The predominant questions that require further attention with respect to atrial fibrillation and heart failure are whether catheter ablation and rhythm control offers benefit in a high-risk heart failure population with respect to mortality or heart failure reduction, and whether cardiac resynchronization therapy implantation truly benefits the subgroup of candidate patients with permanent atrial fibrillation. Large randomized multicentre studies are currently ongoing to address these important questions.

Reduced Uptake of Family Screening in Genotype-Negative Versus Genotype-Positive Long QT Syndrome.

The acceptance and yield of family screening in genotype-negative long QT syndrome (LQTS) remains incompletely characterized. In this study of family screening for phenotype-definite Long QT Syndrome (LQTS, Schwartz score ≥3.5), probands at a regional Inherited Cardiac Arrhythmia clinic were reviewed. All LQTS patients were offered education by a qualified genetic counselor, along with materials for family screening including electronic and paper correspondence to provide to family members. Thirty-eight qualifying probands were identified and 20 of these had family members who participated in cascade screening. The acceptance of screening was found to be lower among families without a known pathogenic mutation (33 vs. 77 %, p = 0.02). A total of 52 relatives were screened; fewer relatives were screened per index case when the proband was genotype-negative (1.7 vs. 3.1, p = 0.02). The clinical yield of screening appeared to be similar irrespective of gene testing results (38 vs. 33 %, p = 0.69). Additional efforts to promote family screening among gene-negative long QT families may be warranted.