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.).

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.

Perioperative Safety and Early Patient and Device Outcomes Among Subcutaneous Versus Transvenous Implantable Cardioverter Defibrillator Implantations : A Randomized, Multicenter Trial.

BACKGROUND: Implantable cardioverter defibrillators (ICDs) improve survival in patients at risk for cardiac arrest, but are associated with intravascular lead-related complications. The subcutaneous ICD (S-ICD), with no intravascular components, was developed to minimize lead-related complications. OBJECTIVE: To assess key ICD performance measures related to delivery of ICD therapy, including inappropriate ICD shocks (delivered in absence of life-threatening arrhythmia) and failed ICD shocks (which did not terminate ventricular arrhythmia). DESIGN: Randomized, multicenter trial. (ClinicalTrials.gov: NCT02881255). SETTING: The ATLAS trial. PATIENTS: 544 eligible patients (141 female) with a primary or secondary prevention indication for an ICD who were younger than age 60 years, had a cardiogenetic phenotype, or had prespecified risk factors for lead complications were electrocardiographically screened and 503 randomly assigned to S-ICD (251 patients) or transvenous ICD (TV-ICD) (252 patients). Mean follow-up was 2.5 years (SD, 1.1). Mean age was 49.0 years (SD, 11.5). MEASUREMENTS: The primary outcome was perioperative major lead-related complications. RESULTS: There was a statistically significant reduction in perioperative, lead-related complications, which occurred in 1 patient (0.4%) with an S-ICD and in 12 patients (4.8%) with TV-ICD (-4.4%; 95% CI, -6.9 to -1.9; P = 0.001). There was a trend for more inappropriate shocks with the S-ICD (hazard ratio [HR], 2.37; 95% CI, 0.98 to 5.77), but no increase in failed appropriate ICD shocks (HR, 0.61 (0.15 to 2.57). Patients in the S-ICD group had more ICD site pain, measured on a 10-point numeric rating scale, on the day of implant (4.2 ± 2.8 vs. 2.9 ± 2.2; P < 0.001) and 1 month later (1.3 ± 1.8 vs. 0.9 ± 1.5; P = 0.035). LIMITATION: At present, the ATLAS trial is underpowered to detect differences in clinical shock outcomes; however, extended follow-up is ongoing. CONCLUSION: The S-ICD reduces perioperative, lead-related complications without significantly compromising the effectiveness of ICD shocks, but with more early postoperative pain and a trend for more inappropriate shocks. PRIMARY FUNDING SOURCE: Boston Scientific.

Characterization of arrhythmia substrate to ablate persistent atrial fibrillation (COAST-AF): Randomized controlled trial design and rationale.

BACKGROUND: Atrial low voltage area (LVA) catheter ablation has emerged as a promising strategy for ablation of persistent atrial fibrillation (AF). It is unclear if catheter ablation of atrial LVA increases treatment success rates in patients with persistent AF. OBJECTIVE: The primary aim of this trial is to assess the potential benefit of adjunctive catheter ablation of atrial LVA in addition to pulmonary vein isolation (PVI) in patients with persistent AF, when compared to PVI alone. The secondary aims are to evaluate safety outcomes, the quality of life and the healthcare resource utilization. METHODS/DESIGN: A multicenter, prospective, parallel-group, 2-arm, single-blinded randomized controlled trial is under way (NCT03347227). Patients who are candidates for catheter ablation for persistent AF will be randomly assigned (1:1) to either PVI alone or PVI + atrial LVA ablation. The primary outcome is 18-month documented event rate of atrial arrhythmia (AF, atrial tachycardia or atrial flutter) post catheter ablation. Secondary outcomes include procedure-related complications, freedom from atrial arrhythmia at 12 months, AF burden, need for emergency department visits/hospitalization, need for repeat ablation for atrial arrhythmia, quality of life at 12 and 18 months, ablation time, and procedure duration. DISCUSSION: Characterization of Arrhythmia Mechanism to Ablate Atrial Fibrillation (COAST-AF) is a multicenter randomized trial evaluating ablation strategies for catheter ablation. We hypothesize that catheter ablation of atrial LVA in addition to PVI will result in higher procedural success rates when compared to PVI alone in patients with persistent AF.

Augmented wide area circumferential catheter ablation for reduction of atrial fibrillation recurrence (AWARE) trial: Design and rationale.

BACKGROUND: Recurrence of atrial fibrillation (AF) after a pulmonary vein isolation procedure is often due to electrical reconnection of the pulmonary veins. Repeat ablation procedures may improve freedom from AF but are associated with increased risks and health care costs. A novel ablation strategy in which patients receive "augmented" ablation lesions has the potential to reduce the risk of AF recurrence. OBJECTIVE: The Augmented Wide Area Circumferential Catheter Ablation for Reduction of Atrial Fibrillation Recurrence (AWARE) Trial was designed to evaluate whether an augmented wide-area circumferential antral (WACA) ablation strategy will result in fewer atrial arrhythmia recurrences in patients with symptomatic paroxysmal AF, compared with a conventional WACA strategy. METHODS/DESIGN: The AWARE trial was a multicenter, prospective, randomized, open, blinded endpoint trial that has completed recruitment (ClinicalTrials.gov NCT02150902). Patients were randomly assigned (1:1) to either the control arm (single WACAlesion set) or the interventional arm (augmented- double WACA lesion set performed after the initial WACA). The primary outcome was atrial tachyarrhythmia (AA; atrial tachycardia [AT], atrial flutter [AFl] or AF) recurrence between days 91 and 365 post catheter ablation. Patient follow-up included 14-day continuous ambulatory ECG monitoring at 3, 6, and 12 months after catheter ablation. Three questionnaires were administered during the trial- the EuroQuol-5D (EQ-5D) quality of life scale, the Canadian Cardiovascular Society Severity of Atrial Fibrillation scale, and a patient satisfaction scale. DISCUSSION: The AWARE trial was designed to evaluate whether a novel approach to catheter ablation reduced the risk of AA recurrence in patients with symptomatic paroxysmal AF.

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.).

Rationale and design of the randomized prospective ATLAS study: Avoid Transvenous Leads in Appropriate Subjects.

BACKGROUND: The defibrillator lead is the weakest part of the transvenous (TV) implantable cardioverter defibrillation (ICD) system and a frequent cause of morbidity. Lead dislodgement, cardiac perforation, insertion-related trauma including pneumothorax and vascular injury, are common early complications of TV-ICD implantation. Venous occlusion, tricuspid valve dysfunction, lead fracture and lead insulation failure are additional, later complications. The introduction of a totally sub-cutaneous ICD (S-ICD) may reduce these lead-related issues, patient morbidity, hospitalizations and costs. However, such benefits compared to the TV-ICD have not been demonstrated in a randomized trial. DESIGN: ATLAS (Avoid Transvenous Leads in Appropriate Subjects) is a multi-centered, randomized, open-label, parallel group trial. Patients younger than 60 years are eligible. If older than 60 years, patients are eligible if they have an inherited heart rhythm disease, or risk factors for ICD-related complication, such as hemodialysis, a history of ICD or pacemaker infection, heart valve replacement, or severe pulmonary disease. This study will determine if using an S-ICD compared to a TV-ICD reduces a primary composite outcome of perioperative complications including pulmonary or pericardial perforation, lead dislodgement or dysfunction, tricuspid regurgitation and ipsilateral venous thrombosis. Five hundred patients will be enrolled from 14 Canadian hospitals, and data collected to both early- (at 6 months) and mid-term complications (at 24 months) as well as mortality and ICD shock efficacy. SUMMARY: The ATLAS randomized trial is comparing early- and mid-term vascular and lead-related complications among S-ICD versus TV-ICD recipients who are younger or at higher risk of ICD-related complications.

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.

Effect of Aggressive Blood Pressure Control on the Recurrence of Atrial Fibrillation After Catheter Ablation: A Randomized, Open-Label Clinical Trial (SMAC-AF [Substrate Modification With Aggressive Blood Pressure Control]).

BACKGROUND: Radiofrequency catheter ablation for atrial fibrillation has become an important therapy for AF; however, recurrence rates remain high. We proposed to determine whether aggressive blood pressure (BP) lowering prevents recurrent atrial fibrillation (AF) after catheter ablation in patients with AF and a high symptom burden. METHODS: We randomly assigned 184 patients with AF and a BP >130/80 mm Hg to aggressive BP (target <120/80 mm Hg) or standard BP (target <140/90 mm Hg) treatment before their scheduled AF catheter ablation. The primary outcome was symptomatic recurrence of AF/atrial tachycardia/atrial flutter lasting >30 seconds, determined 3 months beyond catheter ablation by a blinded end-point evaluation. RESULTS: The median follow-up was 14 months. At 6 months, the mean systolic BP was 123.2±13.2 mm Hg in the aggressive BP treatment group versus 135.4±15.7 mm Hg (P<0.001) in the standard treatment group. The primary outcome occurred in 106 patients, 54 (61.4%) in the aggressive BP treatment group compared with 52 (61.2%) in the standard treatment group (hazard ratio=0.94; 95% confidence interval, 0.65-1.38; P=0.763). In the prespecified subgroup analysis of the influence of age, patients ≥61 years of age had a lower primary outcome event rate with aggressive BP (hazard ratio=0.58; 95% confidence interval, 0.34-0.97; P=0.013). There was a higher rate of hypotension requiring medication adjustment in the aggressive BP group (26% versus 0%). CONCLUSIONS: In this study, this duration of aggressive BP treatment did not reduce atrial arrhythmia recurrence after catheter ablation for AF but resulted in more hypotension. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00438113.

Intracardiac ablation for atrioventricular nodal reentry tachycardia using a 6 mm distal electrode cryoablation catheter: Prospective, multicenter, North American study (ICY-AVNRT STUDY).

INTRODUCTION: Radiofrequency (RF) ablation is effective for slow pathway ablation, but carries a risk of inadvertent AV block requiring permanent pacing. By comparison, cryoablation with a 4-mm distal electrode catheter has not been reported to cause permanent AV block but has been shown to be less effective than RF ablation. We sought to define the safety and efficacy of a 6-mm distal electrode cryoablation catheter for slow pathway ablation in patients with atrioventricular nodal reentry tachycardia (AVNRT). METHODS AND RESULTS: Twenty-six U.S. and eight Canadian centers participated in the study. Patients with supraventricular tachycardia (SVT) thought likely to be AVNRT were enrolled. If AVNRT was inducible and confirmed to be the clinical SVT, then the slow pathway was targeted with a cryoablation catheter using a standardized protocol of best practices. Acute success was defined as inducibility of no more than one echo beat after cryoablation. Primary efficacy was defined as acute success and the absence of documented recurrent AVNRT over 6 months of follow-up. Primary safety was a composite of serious procedure-related adverse events and/or device-related complications. Note that 397 subjects met enrollment criteria after the EP study and received cryoablation. Mean ablation procedure duration (including a waiting period) was 89 ± 40 minutes, and mean fluoroscopy time was 4.8 ± 5.9 minutes. Isoproterenol was administered before cryoablation in 53% and after the last lesion in 85% of cases. Acute procedural success was realized in 95% (378 of 397) of subjects. No subject received a permanent pacemaker due to AV block. The slow pathway could not be ablated in 19 subjects, including: 12 due to inefficacy, 2 due to transient AV block, and 5 due to both inefficacy and transient AV block. RF ablation was used in the same procedure in 11 of 19 failed subjects, and was ineffective in 3 subjects. Among the group with acute success, 10 subjects (2.7%) had documented recurrent AVNRT over the 6-month follow-up period, and all occurred within 3 months of the index cryoablation. Serious procedure-related adverse events occurred in 4 subjects (1.0%), including one each: tamponade, pulmonary embolism, femoral vein hemorrhage, and diagnostic EP catheter knotting. None of these serious adverse events were related to use of the cryoablation catheter. Overall, 93% of subjects had successful slow pathway ablation at 6 months with the study cryoablation catheter. CONCLUSIONS: Cryoablation for AVNRT using a focal 6-mm catheter was safe and effective. It resulted in a low risk of recurrence over 6 months of follow-up with no incidence of AV block requiring permanent pacing.

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.

Intracardiac echo-facilitated 3D electroanatomical mapping of ventricular arrhythmias from the papillary muscles: assessing the 'fourth dimension' during ablation.

AIMS: Ventricular arrhythmias (VA) originating from a papillary muscle (PM) have recently been described as a distinct clinical entity with peculiar features that make its treatment with catheter ablation challenging. Here, we report our experience using an intracardiac echo-facilitated 3D electroanatomical mapping approach in a case series of patients undergoing ablation for PM VA. METHODS AND RESULTS: Sixteen patients who underwent catheter ablation for ventricular tachycardia (VT) or symptomatic premature ventricular contractions originating from left ventricular PMs were included in the study. A total of 24 procedures (mean 1.5 per patient) were performed: 15 using a retrograde aortic approach and 9 using a transseptal approach. Integrated intracardiac ultrasound for 3D electroanatomical mapping was used in 15 of the 24 procedures. The posteromedial PM was the most frequent culprit for the clinical arrhythmia, and the body was the part of the PM most likely to be the successful site for ablation. The site of ablation was identified based on the best pace map matching the clinical arrhythmia and the site of earliest the activation. At a mean follow-up of 10.5 ± 7 months, only two patients had recurrent arrhythmias following a repeat ablation procedure. CONCLUSION: An echo-facilitated 3D electroanatomical mapping allows for real-time creation of precise geometries of cardiac chambers and endocavitary structures. This is useful during procedures such as catheter ablation of VAs originating from PMs, which require detailed representation of anatomical landmarks. Routine adoption of this technique should be considered to improve outcomes of PM VA ablation.

Recent advances in ablation of ventricular tachycardia associated with structural heart disease: overcoming the challenges of functional and fixed barriers.

PURPOSE OF REVIEW: Ablation of ventricular tachycardia in structural heart disease has evolved to include techniques to ablate the myocardial substrate in sinus rhythm for ventricular tachycardias that are noninducible or hemodynamically unstable. The intricacies of the complex functional and fixed components of the myocardial scar involved in the arrhythmic mechanisms require careful consideration in identifying targets for substrate ablation identified in sinus rhythm. RECENT FINDINGS: The substrate ablation approach referred to as 'scar homogenization' aims to thoroughly abolish any abnormal electrical activity inside the scar. However, this extensive approach may target bystander abnormal activity that is not necessarily related to arrhythmias. Recently, different substrate ablation strategies have been developed to more selectively target areas of the scar responsible for ventricular tachycardia. New technologies have also been introduced to provide offline analysis of the electroanatomical substrate, and to improve high-density mapping of the myocardial scar. SUMMARY: Recent advances have improved the ability to ablate ventricular tachycardia using techniques that allow targeting the responsible myocardial substrate while in sinus rhythm. Further research using higher-density mapping with more sophisticated online and offline analysis will aid in the assessment of the complex arrhythmogenicity of the scar and improve efficacy of ventricular tachycardia ablation.

A Historical Perspective on the Role of Functional Lines of Block in the Re-entrant Circuit of Ventricular Tachycardia.

The ablation strategy for ventricular tachycardia (VT) rapidly evolved from an entrainment mapping approach for identification of the critical isthmus of the re-entrant circuit during monomorphic VT, toward a substrate-based approach aiming to ablate surrogate markers of the circuit during sinus rhythm in hemodynamically nontolerated and polymorphic VT. The latter approach implies an assumption that the circuits responsible for the arrhythmia are anatomical or fixed, and present during sinus rhythm. Accordingly, the lines of block delimiting the channels of the circuits are often considered fixed, although there is evidence that they are functional or more frequently a combination of fixed and functional. The electroanatomical substrate-based approach to VT ablation performed during sinus rhythm is increasingly adopted in clinical practice and often described as scar homogenization, scar dechanneling, or core isolation. However, whether the surrogate markers of the VT circuit during sinus rhythm match the circuit during arrhythmias remains to be fully demonstrated. The myocardial scar is a heterogeneous electrophysiological milieu with complex arrhythmogenic mechanisms that potentially coexist simultaneously. Moreover, the scar consists of different areas of diverse refractoriness and conduction. It can be misleading to limit the arrhythmogenic perspective of the myocardial scar to fixed or anatomical barriers held responsible for the re-entry circuit. Greater understanding of the role of functional lines of block in VT and the validity of the surrogate targets being ablated is necessary to further improve the technique and outcome of VT ablation.

Arrhythmic Risk Following Recovery of Left Ventricular Ejection Fraction in Patients with Primary Prevention ICD.

BACKGROUND: Left ventricular ejection fraction (LVEF) recovers during follow-up in a significant proportion of patients implanted with a cardioverter defibrillator (ICD) for primary prevention. Little is known about the midterm arrhythmic risk in this population, particularly in relation to the presence or absence of ischemic cardiomyopathy. METHODS AND RESULTS: We retrospectively analyzed 286 patients with an ICD implanted for primary prevention between 2002 and 2010. Patients were divided into two groups based on their last LVEF assessment: (1) Recovery, defined as an LVEF > 35%; and (2) No-Recovery, defined as an LVEF ≤ 35%. Kaplan-Meir curves and multivariate Cox regression analysis were performed separately for patients with ischemic (211 patients) and nonischemic (75 patients) cardiomyopathy. Forty-nine patients (17.1%) had LVEF recovery to >35% at last follow-up. Overall, 72 patients (25.2%) experienced ventricular arrhythmias requiring ICD therapy during a median follow-up of 4.4 years. With multivariate Cox regression, LVEF recovery was associated with a lower arrhythmic risk in the whole cohort (hazard ratio [HR]: 0.38 [0.13-0.85]; P = 0.02) and in the nonischemic cardiomyopathy cohort (HR: 0.10 [0.005-0.55]; P = 0.005), but not in the ischemic cardiomyopathy cohort (HR: 0.84 [0.25-2.10]; P = 0.74). CONCLUSION: In conclusion, patients with nonischemic cardiomyopathy who improved their LVEF to >35% after primary prevention ICD implantation were at very low absolute arrhythmic risk. Our study raises the possibility that the LVEF cutoff to safely withhold ICD replacement might be higher in patients with ischemic compared to nonischemic cardiomyopathy. This will need to be confirmed in prospective studies.

Real-life experience with a new anticoagulation regimen for patients undergoing left-sided ablation procedures.

BACKGROUND: Current guidelines for anticoagulation during left-sided procedures recommend the administration of unfractionated heparin (UFH) with an initial bolus of 50-100 U/kg, followed by continuous infusion to maintain an activated clotting time (ACT) ≥ 300 s. Our objective was to compare the effectiveness of this standard regimen (100 U/kg bolus) to a more aggressive approach (200 U/kg bolus). METHODS: We collected data on a series of consecutive patients undergoing left sided ablation procedures. Patients with an INR ≥2.0 on the day of the procedure were excluded. Procedural anticoagulation was performed using one of two UFH regimens: 1) 100 U/kg bolus, followed by 10 U/kg/hour infusion or 2) 200 U/kg bolus, followed by 20 U/kg/hour infusion. ACT was measured 10 min after the second bolus and then controlled every 20 min. Heparin was titrated throughout the procedure to maintain an ACT 300-400 s. RESULTS: 145 consecutive patients were included in the study: 34 received an initial bolus of 100 U/kg and 111 received 200 U/kg. The mean time required to reach an ACT ≥300 s was 15.25 min (95% CI 12.97-17.03) in the 200 U/kg group and 51.23 min (95% CI 40.65-61.81) in the 100 U/kg group (p < 0.001). There was no difference between groups with regard to thromboembolic or hemorrhagic complications. CONCLUSION: Current anticoagulation guidelines for left-sided ablation procedures almost universally fail to achieve an initial ACT ≥300 s. A 200 U/kg heparin bolus is much more effective to promptly reach the target ACT, with a low rate of overshoot.

The retrograde P-wave theory: explaining ST segment depression in supraventricular tachycardia by retrograde AV node conduction.

BACKGROUND: Pseudo ischemic ST segment changes during supraventricular tachycardia (SVT) are not yet fully understood. Our aim was to determine whether venticulo-atrial (VA) conduction during SVT may be a possible mechanism for ST depression (STd) in SVT. METHODS: Patients undergoing SVT ablation (2010-2012) were analyzed (n = 72).Typical atrioventricular node reentrant tachycardia (AVNRT) and atrioventricular reentrant tachycardia (AVRT) were included. Those with STd were compared to those without STd. VA interval length, tachycardia cycle length (TCL), and retrograde P-wave activation during SVT were assessed. Retrograde P waves arriving simultaneously with the ST segment (PWST) during SVT were considered, whenever an atrial electrogram (measured from the high right atrium) was "on time" with the ST segment. RESULTS: Patients with STd during SVT presented longer VA intervals than those without STd (VA 100 ± 37 ms vs VA 69 ± 22 ms; P = 0.006). No differences in TCL were observed (TCL 333 ± 35 ms vs TCL 360 ± 22 ms; P = 0.1). PWST was observed in 38.5% of patients with AVNRT and STd versus 0% in those without STd. The TCL was similar in both groups (355 ± 25 ms vs 334 ± 18 ms; P = 0.1). In patients with AVRT and STd, PWST was present in 81% of cases versus 0% in those without STd. The TCL was also similar (330 ± 29 ms vs 346 ± 17 ms; P = 0.1). CONCLUSIONS: STd during SVT is observed at long VA intervals when the retrograde P wave matches the ST segment, without dependence on the TCL. This suggests that STd is not necessarily rate dependent but a result of a fusion between the ST segment and the P wave.