Atrial Fibrillation Ablation in Heart Failure With Reduced vs Preserved Ejection Fraction: A Systematic Review and Meta-Analysis.

Importance: Catheter ablation is associated with reduced heart failure (HF) hospitalization and death in select patients with atrial fibrillation (AF) and heart failure with reduced ejection fraction (HFrEF). However, the benefit in patients with HF with preserved ejection fraction (HFpEF) is uncertain. Objective: To investigate whether catheter ablation for AF is associated with reduced HF-related outcomes according to HF phenotype. Data Source: A systematic search of MEDLINE, Embase, and Cochrane Central was conducted among studies published from inception to September 2023. Study Selection: Parallel-group randomized clinical trials (RCTs) comparing catheter ablation with conventional rate or rhythm control therapies in patients with HF, New York Heart Association functional class II or greater, and a history of paroxysmal or persistent AF were included. Pairs of independent reviewers screened 7531 titles and abstracts, of which 12 RCTs and 4 substudies met selection criteria. Data Extraction and Synthesis: Data were abstracted in duplicate according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Pooled effect estimates were calculated using random-effects Mantel-Haenszel models. Interaction P values were used to test for subgroup differences. Main Outcomes and Measures: The primary outcome was HF events, defined as HF hospitalization, clinically significant worsening of HF, or unscheduled visits to a clinician for treatment intensification. Secondary outcomes included cardiovascular and all-cause mortality. Results: A total of 12 RCTs with 2465 participants (mean [SD] age, 65.3 [9.7] years; 658 females [26.7%]) were included; there were 1552 participants with HFrEF and 913 participants with HFpEF. Compared with conventional rate or rhythm control, catheter ablation was associated with reduced risk of HF events in HFrEF (risk ratio [RR], 0.59; 95% CI, 0.48-0.72), while there was no benefit in patients with HFpEF (RR, 0.93; 95% CI, 0.65-1.32) (P for interaction = .03). Catheter ablation was associated with reduced risk of cardiovascular death compared with conventional therapies in HFrEF (RR, 0.49; 95% CI, 0.34-0.70) but a differential association was not detected in HFpEF (RR, 0.91; 95% CI, 0.46-1.79) (P for interaction = .12). Similarly, no difference in the association of catheter ablation with all-cause mortality was found between HFrEF (RR vs conventional therapies, 0.63; 95% CI, 0.47-0.86) and HFpEF (RR vs conventional therapies, 0.95; 95% CI, 0.39-2.30) groups (P for interaction = .39). Conclusions and Relevance: This study found that catheter ablation for AF was associated with reduced risk of HF events in patients with HFrEF but had limited or no benefit in HFpEF. Results from ongoing trials may further elucidate the role of catheter ablation for AF in HFpEF.

A Randomized Clinical Trial of Catheter Ablation and Antiarrhythmic Drug Therapy for Suppression of Ventricular Tachycardia in Ischemic Cardiomyopathy: The VANISH2 Trial.

Recurrent ventricular tachycardia (VT) in patients with prior myocardial infarction is associated with adverse quality of life and clinical outcomes, despite the presence of implanted defibrillators (ICDs). Suppression of recurrent VT can be accomplished with antiarrhythmic drug therapy or catheter ablation. The Ventricular Tachycardia Antiarrhythmics or Ablation In Structural Heart Disease 2 (VANISH2) trial is designed to determine whether ablation is superior to antiarrhythmic drug therapy as first line therapy for patients with ischemic cardiomyopathy and VT. The VANISH2 trial enrolls patients with prior myocardial infarction and VT (with one of: ≥1 ICD shock; ≥3 episodes treated with antitachycardia pacing (ATP) and symptoms; ≥5 episodes treated with ATP regardless of symptoms; ≥3 episodes within 24 hours; or sustained VT treated with electrical cardioversion or pharmacologic conversion). Enrolled patients are classified as either sotalol-eligible, or amiodarone-eligible, and then are randomized to either catheter ablation or to that antiarrhythmic drug therapy, with randomization stratified by drug-eligibility group. Drug therapy, catheter ablation procedures and ICD programming are standardized. All patients will be followed until two years after randomization. The primary endpoint is a composite of mortality at any time, appropriate ICD shock after 14 days, VT storm after 14 days, and treated sustained VT below detection of the ICD after 14 days. The outcomes will be analyzed according to the intention-to-treat principle using survival analysis techniques. The results of the VANISH2 trial are intended to provide data to support clinical decisions on how to suppress VT for patients with prior myocardial infarction. Clinicaltrials.gov registration NCT02830360.

Long-Term Outcomes of Resynchronization-Defibrillation for Heart Failure.

BACKGROUND: The Resynchronization-Defibrillation for Ambulatory Heart Failure Trial (RAFT) showed a greater benefit with respect to mortality at 5 years among patients who received cardiac-resynchronization therapy (CRT) than among those who received implantable cardioverter-defibrillators (ICDs). However, the effect of CRT on long-term survival is not known. METHODS: We randomly assigned patients with New York Heart Association (NYHA) class II or III heart failure, a left ventricular ejection fraction of 30% or less, and an intrinsic QRS duration of 120 msec or more (or a paced QRS duration of 200 msec or more) to receive either an ICD alone or a CRT defibrillator (CRT-D). We assessed long-term outcomes among patients at the eight highest-enrolling participating sites. The primary outcome was death from any cause; the secondary outcome was a composite of death from any cause, heart transplantation, or implantation of a ventricular assist device. RESULTS: The trial enrolled 1798 patients, of whom 1050 were included in the long-term survival trial; the median duration of follow-up for the 1050 patients was 7.7 years (interquartile range, 3.9 to 12.8), and the median duration of follow-up for those who survived was 13.9 years (interquartile range, 12.8 to 15.7). Death occurred in 405 of 530 patients (76.4%) assigned to the ICD group and in 370 of 520 patients (71.2%) assigned to the CRT-D group. The time until death appeared to be longer for those assigned to receive a CRT-D than for those assigned to receive an ICD (acceleration factor, 0.80; 95% confidence interval, 0.69 to 0.92; P = 0.002). A secondary-outcome event occurred in 412 patients (77.7%) in the ICD group and in 392 (75.4%) in the CRT-D group. CONCLUSIONS: Among patients with a reduced ejection fraction, a widened QRS complex, and NYHA class II or III heart failure, the survival benefit associated with receipt of a CRT-D as compared with ICD appeared to be sustained during a median of nearly 14 years of follow-up. (RAFT ClinicalTrials.gov number, NCT00251251.).

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.

Achieving bi-directional conduction block during catheter ablation is not enough to prevent recurrence of cavo-tricuspid isthmus dependant atrial flutter: Role of subclinical conduction.

BACKGROUND: Achieving bi-directional conduction block, as assessed by differential pacing and change in activation along tricuspid annulus (TA), across the cavo-tricuspid isthmus (CTI), is considered a satisfactory end point during catheter ablation of atrial flutter (AFL). AIM: To assess role of subclinical conduction by observing polarity reversal of local bipolar signals from RS to QR pattern lateral to the line of ablation, in predicting recurrence of CTI dependant AFL after ablation in patients with bidirectional conduction block. METHOD AND RESULTS: Of 683 patients undergoing ablation of CTI dependent AFL, 73 (10.6%) patients underwent redo flutter ablation and were evaluated further. The mean age was 60.8 years and 51% were males. Evidence of bidirectional block by differential pacing and change is activation along multipolar catheter and reversal of local bipolar signals from RS to QR pattern lateral to the line of ablation, during the 1st and subsequent procedure, were studied. 60% patients had confirmed bidirectional block of which 71% had lack of voltage reversal, at the end of 1st procedure. All patients with bidirectional block with lack of reversal of bipolar signals, after the first procedure had recurrence of AFL whereas only 3/11 (27%) people with bidirectional block and with absence of subclinical conduction had recurrence of AFL. CONCLUSION: Achieving bidirectional conduction block is not sufficient to prevent recurrence of AFL after CTI ablation. Reversal of local bipolar signals, from RS to QR pattern along with achieving bidirectional conduction delay would reduce recurrence of AFL, post ablation.

Influence of the Social Environment on Ideal Cardiovascular Health.

Background The environment plays a large role in the health of individuals; however, more research is needed to better understand aspects of the environment that most influence health. Specifically, our study examines how the social environment influences cardiovascular health (CVH). Methods and Results The social environment was characterized using measures of belonging and life and work stress in individuals, as well as nationally derived measures of marginalization, deprivation, economic status, and community well-being in neighborhoods. CVH was defined by the American Heart Association's Cardiovascular Health Index-a summed score of 7 clinical and behavioral components known to have the greatest impact on CVH. Data were obtained from the Canadian Community Health Survey 2015 to 2016 and multiple national data sources. Multilevel regression models were used to analyze the associations between CVH and the social environment. Overall, 27% of Canadians reported ideal CVH (6-7 score points), 68% reported intermediate CVH (3-5 score points), and 5% reported poor CVH (0-2 score points). The neighborhood environment contributed up to 7% of the differences in CVH between individuals. Findings indicated that residing in a neighborhood with greater community well-being (odds ratio [OR], 1.33 [95% CI, 1.26-1.41]) was associated with achieving higher odds of ideal CVH, while weaker community belonging (OR, 0.67 [95% CI, 0.62-0.72]) and residing in a neighborhood with greater marginalization (OR, 0.87 [95% CI, 0.82-0.91]) and deprivation (OR, 0.67 [95% CI, 0.64-0.69]) were associated with achieving lower odds of ideal CVH. Conclusions Aspects of individual-level social environment and residing in a neighborhood with a more favorable social environment were both independently and significantly associated with achieving ideal CVH.

Is Maintenance of Sinus Rhythm of Value in Patients with Atrial Fibrillation and Heart Failure?

PURPOSE OF REVIEW: Heart failure (HF) and atrial fibrillation (AF) frequently co-exist, with the prevalence of AF increasing in patients with more advanced HF symptoms. When present, AF increases morbidity and mortality in patients with HF. The purpose of this review is to examine emerging evidence addressing the value of restoration and maintenance of sinus rhythm in patients with HF. RECENT FINDINGS: Earlier trials comparing a rhythm control strategy with antiarrhythmic drugs have failed to demonstrate benefit in patients with HF and reduced ejection fraction. More recent trials, including the recently published RAFT-AF, utilizing catheter ablation for rhythm control, have shown greater promise, possibly due to reduced medication-related side effects and higher efficacy in maintaining sinus rhythm. A strategy of sinus rhythm maintenance with catheter ablation appears to improve mortality, reduce HF events and improve quality of life in patients with AF and HF.

Hemodynamically Tolerated Ventricular Tachycardia With Mildly Impaired Ejection Fraction: Do These Patients Have VT/VF Recurrence and ICD Therapies?

BACKGROUND: Patients with hemodynamically tolerated ventricular tachycardia (VT) and minimally reduced left ventricular ejection fraction (LVEF) remain a group that presents a prognostic and therapeutic dilemma. METHODS: We studied patients from our implanted cardioverter-defibrillator (ICD) database who received ICDs for hemodynamically tolerated VT and mildly reduced LVEF (36%-49%) at time of implant between May 2015 and December 2019. Time to appropriate ICD therapy was assessed. Clinical features associated with recurrent VT/ventricular fibrillation (VF) with ICD therapies were explored using binary logistic regression. RESULTS: Among 2037 ICDs placed between May 2015 and December 2019, 64 subjects met the inclusion criteria. The mean age of the study group was 68 ± 12 years, and 58 (90.6%) subjects were male. Average ejection fraction was 40% ± 4.4 (range 36%-49%). Twenty-two (34%) subjects received antitachycardia pacing (ATP) for VT at 229 ± 265 days after ICD placement. Fifteen (23%) subjects received appropriate ICD shocks 305 ± 321 days after implant. The rate of recurrent VT/VF among the 37 patients with ICD therapy was 195 ± 39 beats per minute (bpm). This was significantly more rapid than initial presenting VT rates before ICD placement (183 ± 27 bpm) (P = 0.048). Multivariate analysis showed no factors independently associated with recurrent VT/VF. CONCLUSIONS: Patients with mildly impaired LV function and hemodynamically tolerated VT receive appropriate ICD therapies over the 3 years following implant. This patient group warrants further investigation, as their recurrent VT/VF rates can be much more rapid, and 23% go on to receive appropriate ICD shocks.

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.

Quality of Life and Health Care Utilization in the CIRCA-DOSE Study.

OBJECTIVES: This study evaluated the impact of contact force-guided radiofrequency ablation versus cryoballoon ablation on quality of life and health care utilization. BACKGROUND: Traditional outcome parameters, such as arrhythmia-free survival, are insufficient to evaluate the clinical impact of atrial fibrillation (AF), as it fails to the capture patient- and health system-level differences in treatment approaches. METHODS: The CIRCA-DOSE (Cryoballoon Vs. Contact-Force Atrial Fibrillation Ablation) study randomly assigned 346 patients with drug-refractory paroxysmal AF to contact force-guided radiofrequency or cryoballoon ablation. Health-related quality-of-life (HRQOL) was assessed at baseline, and at 6 and 12 months post-ablation using a disease-specific and generic HRQOL instruments. Health care utilization (hospitalization, emergency department visits, and cardioversion) and antiarrhythmic drug use for the 12 months preceding ablation was compared with the 12 months following ablation. RESULTS: Disease-specific and generic HRQOL was moderately to severely impaired at baseline and improved significantly at 6 and 12 months of follow-up (median improvement in AFEQT [Atrial Fibrillation Effect on QualiTy of Life] score 32.4 [interquartile range: 17.7 to 48.9]). When compared with the 12 months pre-ablation, the proportion and absolute number of cardioversions decreased significantly (41.1% vs. 10.1% of patients, 137 vs. 35 events; p < 0.0001). Similar significant reductions in emergency department visits (66.7% vs. 25.1% of patients, 224 vs. 87 events; p < 0.0001), and hospitalizations (25.5% vs. 14.5% of patients, 86 vs. 50 events; p < 0.001) were observed. There were no significant differences between randomized groups. CONCLUSIONS: In this multicenter randomized trial, catheter ablation with advanced-generation technologies resulted in a significant improvement in HRQOL and a significant reduction in health care utilization in the year following AF ablation. (Cryoballoon vs. Irrigated Radiofrequency Catheter Ablation [CIRCA-DOSE]; NCT01913522).

Virtual follow-up and care for patients with cardiac electronic implantable devices: protocol for a systematic review.

BACKGROUND: Capacity to deliver outpatient care for patients with cardiac implantable electronic devices (CIEDs) may soon be outweighed by need. This systematic review aims to investigate the comparative effectiveness, safety, and cost for virtual or remote clinic interventions for patients with CIEDs and explores how outcomes may be influenced by patient or system factors in-depth. METHODS: We will perform a systematic literature search in MEDLINE, Embase, PsycINFO, CINAHL, Proquest Dissertations & Theses, other EBM Reviews, and trial registry databases. Two authors will independently screen titles and abstracts for eligibility. We will include randomized and non-randomized controlled trials, quasi-randomized and experimental studies, cohort, and case-control studies. Study populations of interest are individuals with a CIED (pacemaker, ICD, CRT). Eligibility will be restricted to virtual or remote follow-up or care interventions compared to any other approach. The co-primary outcomes of interest are mortality and patient satisfaction. Secondary outcomes include clinical effectiveness (e.g., ICD shock, time-to-detection of medical event, hospitalizations), safety (e.g., serious or device-related adverse events), device efficacy (e.g., transmissions, malfunctions), costs, workflow (e.g., resources, process outcomes, time-saved), and patient reported (e.g., burden, quality of life). Data will be extracted by one author and checked by a second using a standardized template. We will use published frameworks to capture data relevant to intervention effects that may be influenced by intervention definition or complexity, context and setting, or in socially disadvantaged populations. Detailed descriptive results will be presented for all included studies and outcomes, and where feasible, synthesized using meta-analysis. Risk of bias will be assessed by two review authors independently using Cochrane Risk of Bias tools. Certainty of evidence will be assessed using the GRADE approach. DISCUSSION: Increases in number of CIEDs implanted, combined with an aging population and finite health resource allocations at the system-level may lead to increased reliance on virtual follow-up or care models in the future. These models must prioritize consistent, equitable, and timely care as a priority. Results from this systematic review will provide important insight into the potential contextual factors which moderate or mediate the effectiveness, safety, and cost of virtual follow-up or care models for patients. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration number CRD42020145210.

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.

Atrial Fibrillation and Heart Failure: Untangling a Modern Gordian Knot.

Heart failure (HF) and atrial fibrillation (AF) share common risk factors and frequently coexist. Both are highly prevalent in our aging population, and mortality associated with the combination is significantly higher than for each alone. An intricate link exists between AF and HF, including interrelated mechanisms and pathophysiology. Asymptomatic left ventricular systolic or diastolic dysfunction can exacerbate or be exacerbated by AF, resulting in HF with reduced ejection fraction or preserved ejection fraction. A number of treatment strategies have improved symptoms, exercise tolerance, and quality of life for patients with HF, but few have resulted in alteration in prognosis. Sinus rhythm, achieved pharmacologically, has not altered important outcomes, including cardiovascular or total mortality in patients with HF. In recent studies, catheter ablation to achieve sinus rhythm seems to have a significant impact on symptoms, heart function, and possibly mortality. Until future studies can confirm or clarify the impact of catheter ablation on outcomes, the field remains cautious but optimistic that better treatment strategies for patients with HF with reduced ejection fraction or preserved ejection fraction are within reach.

Long-term risk of stroke and bleeding post-atrial fibrillation ablation.

BACKGROUND: Catheter ablation (CA) is an established therapy for atrial fibrillation (AF). Studies regarding long-term real-world outcomes post-CA have inconsistently accounted for oral anticoagulation (OAC). OBJECTIVES: To describe patterns of OAC use post-CA and to compare the OAC-adjusted long-term risk of stroke and major bleeding in AF patients with and without CA. METHODS: A population-based cohort of AF patients was constructed in Quebec and Ontario, Canada (1999-2014). Propensity score matching was performed to determine the incidence rates of stroke and major bleeding among those undergoing CA, adjusted for time-dependent OAC use. RESULTS: From the entire cohort, 6391 patients were identified as having undergone CA as compared to 482 977 patients who did not. Of these, 1240 patients with government medical insurance undergoing CA were matched with 2427 patients without CA. Post-CA, 78%, 65%, and 61% remained on an OAC at 1, 2, and 5 years, while 75%, 71%, and 68% of patients not undergoing CA were on OACs at 1, 2, and 5 years. At follow-up, there was no statistically significant difference for stroke (adjusted hazard ratio [HR], 0.88; 95% CI, 0.63 to 1.21) or major bleeding (adjusted HR, 0.88; 95% CI, 0.73 to 1.06). CONCLUSION: No evidence was found that CA significantly decreases the risk of stroke or major bleeding when adjusting for OAC use over time. It may be prudent to continue anticoagulation post-CA based on patient-risk profile until randomized trials demonstrate both reduced stroke rates with CA, and improved safety (balancing stroke and bleeding risk) with OAC discontinuation post-CA.

Cost Effectiveness of Ventricular Tachycardia Ablation Versus Escalation of Antiarrhythmic Drug Therapy: The VANISH Trial.

OBJECTIVES: This analysis uses the data from the randomized controlled trial to assess the cost effectiveness of catheter ablation (n = 132) versus escalated antiarrhythmic therapy (n = 127). BACKGROUND: For survivors of myocardial infarction with implantable cardioverter-defibrillator shocks despite antiarrhythmic drugs, the VANISH (Ventricular Tachycardia Ablation Versus Escalated Antiarrhythmic Drug Therapy in Ischemic Heart Disease) trial demonstrated improved clinical outcomes with catheter ablation compared with more aggressive antiarrhythmic pharmacotherapy. METHODS: Health care resource use and quality-of-life data were used to determine the cost effectiveness of catheter ablation. Published references were used to estimate costs (in 2015 Canadian dollars). The analysis was over 3 years, with a 5% discount rate. Adjustment was made for censoring and baseline utilities. RESULTS: Ablation resulted in greater quality-adjusted life-years (QALYs) than escalated drug therapy did (1.63 vs. 1.49; difference: 0.14; 95% confidence interval [CI]: -0.20 to 0.46) and higher cost ($65,126 vs. $60,269; difference: $4,857; 95% CI: -$19,757 to $27,106); with an incremental cost per QALY gained for ablation versus escalated drug therapy of $34,057 primarily due to the initial costs of ablation, which were partially offset by the costs of subsequent ablations and adverse outcomes in the escalated drug therapy arm. For patients with amiodarone-refractory ventricular tachycardia, ablation dominated escalated drug therapy, with greater QALYs (1.48 vs. 1.26; difference: 0.22; 95% CI: -0.19 to 0.59) and lower costs ($67,614 vs. $68,383; difference: -$769; 95% CI: -$35,330 to $27,092). For those with sotalol-refractory ventricular tachycardia, ablation resulted in similar QALYs (1.90 vs. 1.90; difference: -0.00; 95% CI: -0.59 to 0.62) and higher costs ($60,455 vs. $45,033; difference: $15,422; 95% CI: -$10,968 to $48,555). CONCLUSIONS: For the total trial population, results are suggestive that ablation is cost effective compared with escalation of drug therapy. This result was only manifest for the subgroup of patients whose qualifying arrhythmia occurred despite amiodarone.

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.

The interaction of sex, height, and QRS duration on the effects of cardiac resynchronization therapy on morbidity and mortality: an individual-patient data meta-analysis.

AIMS: To explore possible associations that may explain the greater benefit from cardiac resynchronization therapy (CRT) reported amongst women. METHODS AND RESULTS: In an individual-patient data meta-analysis of five randomized controlled trials, all-cause mortality and the composite of all-cause mortality or first hospitalization for heart failure (HF) were compared among 794 women and 2702 men assigned to CRT or a control group. Multivariable analyses were performed to assess the impact of sex, QRS duration, HF aetiology, left ventricular end-diastolic diameter (LVEDD), and height on outcome. Women were shorter, had smaller LVEDD, more often left bundle branch block, and less often ischaemic heart disease, but QRS duration was similar between sexes. Women tended to obtain greater benefit from CRT but sex was not an independent predictor of either outcome. For all-cause mortality, QRS duration was the only independent predictor of CRT benefit. For the composite outcome, height and QRS duration, but not sex, were independent predictors of CRT benefit. Further analysis suggested increasing benefit with increasing QRS duration amongst shorter patients, of whom a great proportion were women. CONCLUSIONS: In this individual-patient data meta-analysis, CRT benefit was greater in shorter patients, which may explain reports of enhanced CRT benefit among women. Further analyses are required to determine whether recommendations on the QRS threshold for CRT should be adjusted for height. (ClinicalTrials.gov numbers: NCT00170300, NCT00271154, NCT00251251).

Effect of Baseline Antiarrhythmic Drug on Outcomes With Ablation in Ischemic Ventricular Tachycardia: A VANISH Substudy (Ventricular Tachycardia Ablation Versus Escalated Antiarrhythmic Drug Therapy in Ischemic Heart Disease).

BACKGROUND: The VANISH trial (Ventricular Tachycardia Ablation Versus Escalated Antiarrhythmic Drug Therapy in Ischemic Heart Disease) compared the effectiveness of escalated antiarrhythmic drug therapy to catheter ablation in patients with prior myocardial infarction, an implanted defibrillator, and ventricular tachycardia (VT). The effectiveness of these interventions in patients on sotalol versus amiodarone was compared. METHODS AND RESULTS: Analysis was conducted based on whether patients had recurrent VT, despite amiodarone (amio-refractory) or nonamiodarone drugs (sotalol-refractory). Outcomes included death, VT storm, appropriate implantable cardioverter defibrillator shock, and any ventricular arrhythmia. At baseline, 169 (65.2%) were amio-refractory, and 90 (34.7%) were sotalol-refractory (1 patient on procainamide rather than sotalol). Amio-refractory patients had more renal insufficiency (23.7% versus 10%; P=0.0008), worse New York Heart Association class (82.3% II/III versus 65.5%; P=0.0003), and lower ejection fraction (29±9.7% versus 35.2±11%; P<0.0001). Within the amio-refractory group, ablation resulted in reduction of any ventricular arrhythmia compared with escalated drug therapy (hazard ratio, 0.53; 95% confidence interval, 0.31-0.9), P=0.020). Sotalol-refractory patients had trends toward higher mortality and VT storm with ablation, with no effect on implantable cardioverter defibrillator shocks. Within the escalated drug therapy arm, amio-refractory patients had a higher rate of the composite outcome (hazard ratio, 1.94; 95% confidence interval, 1.14-3.29; P=0.0144) and a trend to higher mortality (hazard ratio, 2.40; 95% confidence interval, 0.93-6.22; P=0.07), whereas mortality was not different between amio- and sotalol-refractory patients within the ablation treatment group. CONCLUSIONS: Patients with amio-refractory VT have a higher rate of ventricular arrhythmia and mortality than those with sotalol-refractory VT and derive greater benefit of catheter ablation than for patients with sotalol-refractory VT who are switched to amiodarone. CLINICAL TRIAL REGISTRATION: URL: https://clinicaltrials.gov. Unique identifier: NCT00905853.