Catheter ablation for persistent atrial fibrillation: patterns of recurrence and impact on quality of life and health care utilisation.

BACKGROUND AND AIMS: Patterns of atrial fibrillation (AF) recurrence post catheter ablation for persistent AF are not well described. This study aimed to describe the pattern of AF recurrence seen following catheter ablation for persistent AF (PsAF) and the implications for healthcare utilisation and quality of life. METHODS: This was a post-hoc analysis of the CAPLA study, an international, multi-centre study that randomised patients with symptomatic PsAF to pulmonary vein isolation plus posterior wall isolation or pulmonary vein isolation alone. Patients underwent twice daily single lead ECG, implantable device monitoring or three monthly Holter monitoring. RESULTS: 154 of 333 (46.2%) patients (median age 67.3 years, 28% female) experienced AF recurrence at 12-month follow-up. Recurrence was paroxysmal in 97 (63%) patients and persistent in 57 (37%). Recurrence type did not differ between randomisation groups (p=0.508). Median AF burden was 27.4% in PsAF recurrence and 0.9% in paroxysmal AF (PAF) recurrence (p<0.001). Patients with PsAF recurrence had lower baseline left ventricular ejection fraction (PsAF 50% vs PAF 60%, p<0.001) and larger left atrial volume (PsAF 54.2±19.3 ml/m² vs PAF 44.8±11.6 ml/m², p=0.008). Healthcare utilisation was significantly higher in PsAF (45 patients [78.9%]) vs PAF recurrence (45 patients [46.4%], p<0.001) and lowest in those without recurrence (17 patients [9.5%], p<0.001). Patients without AF recurrence had greater improvements in quality of life as assessed by the Atrial Fibrillation Effect on Quality-of-Life (AFEQT) questionnaire (Δ33.3±25.2 points) compared to those with PAF (Δ24.0±25.0 points, p=0.012) or PsAF (Δ13.4±22.9 points, p<0.001) recurrence. CONCLUSIONS: AF recurrence is more often paroxysmal after catheter ablation for PsAF irrespective of ablation strategy. Recurrent PsAF was associated with higher AF burden, increased healthcare utilisation and antiarrhythmic drug use. The type of AF recurrence and AF burden may be considered important endpoints in clinical trials investigating ablation of PsAF.

Navigating the Landscape of Medical Device Advisories: A Special Report From the Canadian Heart Rhythm Society Device Advisory Committee.

Cardiac implantable electronic devices (CIEDs) are often important for regulating cardiac rate and rhythm. Pacemakers and defibrillators are among the top 10 most implanted medical devices, with > 1.5 million devices implanted annually. Although millions of patients have benefited with improved quality of life and survival, CIED systems are becoming increasingly complex and do not always perform according to expectations. Advisory notices communicate important information about the safety and performance of a medical device to health care providers and patients. Medical device recalls are common, with > 35 unique device recalls in the past 5 years. From an ethical standpoint, CIED recalls highlight a range of considerations including the consent process, duty to report, how best to promote autonomous decision-making, trust in the health care system, as well as disproportionate effects of these considerations on equity-deserving groups. The purpose of the current article is to review and advise regarding the process around medical device advisory and recall, with a specific focus on clinicians caring for patients affected by these devices. We have sought the input of a lawyer, a patient advocacy group, and an ethicist to guide the clinical management of, and communications regarding, device recalls and advisories. Diligent surveillance and a clear, transparent patient consent process regarding these small but potentially serious device anomalies is paramount in ensuring patients believe they are safe and informed. Meaningful patient engagement helps to ensure optimal communication and disclosure mechanisms before implantation and throughout follow-up, accessibility of information in the initial implant and recall action process, and trust in health care systems and providers.

Sex-specific outcomes after catheter ablation for persistent AF.

BACKGROUND: Sex-specific outcomes after catheter ablation (CA) for atrial fibrillation (AF) have reported conflicting findings. OBJECTIVE: We examined the impact of female sex on outcomes in patients with persistent AF (PsAF) from the Catheter Ablation for Persistent Atrial Fibrillation: A Multicentre Randomized Trial of Pulmonary Vein Isolation vs PVI with Posterior Left Atrial Wall Isolation (CAPLA) randomized trial. METHODS: A total of 338 patients with PsAF were randomized to pulmonary vein isolation (PVI) or PVI with posterior wall isolation (PWI). The primary outcome was arrhythmia recurrence at 12 months. Clinical and electroanatomical characteristics, arrhythmia recurrence, and quality of life were compared between women and men. RESULTS: Seventy-nine women (23.4%; PVI 37; PVI + PWI 42) and 259 men (76.6%; PVI 131; PVI + PWI 128) underwent AF ablation. Women were older {median age 70.4 (interquartile range [IQR] 64.8-74.6) years vs 64.0 (IQR 56.7-69.7) years; P < .001} and had more advanced left atrial electroanatomical remodeling. At 12 months, arrhythmia-free survival was lower in women (44.3% vs 56.8% in men; hazard ratio 1.44; 95% confidence interval 1.02-2.04; log-rank, P = .036). PWI did not improve arrhythmia-free survival at 12 months (hazard ratio 1.02; 95% confidence interval 0.74-1.40; log-rank, P = .711). The median AF burden was 0% in both groups (women: IQR 0.0%-2.2% vs men: IQR 0.0%-2.8%; P = .804). Health care utilization was comparable between women (36.7%) and men (30.1%) (P = .241); however, women were more likely to undergo a repeat procedure (17.7% vs 6.9%; P = .007). Women reported more severe baseline anxiety (average Hospital Anxiety and Depression Scale [HADS] anxiety score 7.5 ± 4.9 vs 6.3 ± 4.3 in men; P = .035) and AF-related symptoms (baseline Atrial Fibrillation Effect on Quality-of-Life Questionnaire [AFEQT] score 46.7 ± 20.7 vs 55.9 ± 23.0 in men; P = .002), with comparable improvements in psychological symptoms (change in HADS anxiety score -3.8 ± 4.6 vs -3.0 ± 4.5; P = .152 (change in HADS depression score -2.9 ± 5.0 vs -2.6 ± 4.0; P = .542) and greater improvement in AFEQT score compared with men at 12 months (change in AFEQT score +45.9 ± 23.1 vs +39.2 ± 24.8; P = .048). CONCLUSION: Women undergoing CA for PsAF report more significant symptoms and poorer quality of life at baseline than men. Despite higher arrhythmia recurrence and repeat procedures in women, the AF burden was comparably low, resulting in significant improvements in quality of life and psychological well-being after CA in both sexes.

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.).

Impact of Posterior Left Atrial Voltage on Ablation Outcomes in Persistent Atrial Fibrillation: CAPLA Substudy.

BACKGROUND: Pulmonary vein isolation (PVI) is less effective in patients with persistent atrial fibrillation (PsAF). Adjunctive ablation targeting low voltage areas (LVAs) may improve arrhythmia outcomes. OBJECTIVES: This study aims to compare the outcomes of adding posterior wall isolation (PWI) to PVI, vs PVI alone in PsAF patients with posterior wall LVAs. METHODS: The CAPLA (Effect of Catheter Ablation Using Pulmonary Vein Isolation With vs Without Posterior Left Atrial Wall Isolation on Atrial Arrhythmia Recurrence in Patients With Persistent Atrial Fibrillation) study was a multicenter, randomized trial involving PsAF patients randomized 1:1 to either PVI alone or PVI with PWI. Voltage mapping performed during pacing pre-ablation was reviewed offline, with LVA defined as bipolar voltage of <0.5 mV. The primary endpoint was freedom from any documented atrial arrhythmia of >30 seconds off antiarrhythmic medication at 12 months after a single ablation procedure in patients with posterior LVA. RESULTS: A total of 210 patients (average 64.6 ± 9.2 years,73.3% males, median atrial fibrillation duration 4.5 months [IQR: 2 to 8 months]) underwent multipolar left atrial mapping during coronary sinus pacing with posterior LVA present in 69 (32.9%). Patients with posterior LVA were more likely to have LVA in other atrial regions (91.7% vs 57.1%; P < 0.01), larger left atrial diameter (4.8 cm vs 4.4 cm; P < 0.01), and significantly increased risk of atrial arrhythmia recurrence at 12 months (LVA: 56.5% vs no LVA: 41.4%; HR: 1.51; 95% CI: 1.01-2.27; P = 0.04) compared to no posterior LVA. However, the addition of PWI to PVI did not significantly improve freedom from atrial arrhythmia recurrence over PVI alone (PVI with PWI: 44.8% vs PVI: 41.9%; HR: 0.95; 95% CI: 0.51-1.79; P = 0.95). CONCLUSIONS: In patients with PsAF undergoing catheter ablation, posterior LVA was associated with a significant increase in atrial arrhythmia recurrence. However, the addition of PWI in those with posterior LVA did not reduce atrial arrhythmia recurrence over PVI alone.

Posterior Wall Isolation Improves Outcomes for Persistent AF With Rapid Posterior Wall Activity: CAPLA Substudy.

BACKGROUND: Pulmonary vein isolation (PVI) is less effective in persistent atrial fibrillation (PerAF) than in paroxysmal atrial fibrillation (AF). However, the CAPLA (Effect of Catheter Ablation Using Pulmonary Vein Isolation With vs Without Posterior Left Atrial Wall Isolation on Atrial Arrhythmia Recurrence in Patients With Persistent Atrial Fibrillation: The CAPLA randomized clinical trial) of PVI vs posterior wall isolation (PWI) did not support empiric PWI in PerAF. We examined pulmonary vein (PV) and posterior wall (PW) electrical characteristics to determine if select patients may benefit from additional PWI. OBJECTIVES: This study sought to determine the impact of PV and PW electrical characteristics on AF ablation outcomes in the CAPLA randomized study. METHODS: Participants in spontaneous AF at the time of ablation were included from the CAPLA study. The mean, shortest, and longest PV, PW, and left atrial (LA) appendage cycle length measurements were annotated preablation using a multipolar catheter for 100 consecutive cycles. Next, cardioversion was performed with a high-density LA voltage map completed. Cox proportional hazards regression was utilized to determine clinical and electroanatomic predictors of AF recurrence overall and according to ablation strategy. Follow-up included twice daily single-lead electrocardiograms or continuous monitoring for 12 months. RESULTS: A total of 151 patients (27% female, age 65 ± 9 years, 18% long-standing PerAF, LA volume index 52 ± 16 mL/m2, median AF duration 5 months [IQR: 2-10 months]) were in AF on the day of procedure and were randomized to PVI alone (50%) or PVI+PWI (50%) according to the CAPLA randomized clinical trial protocol. Baseline clinical, echocardiographic, and electroanatomic parameters were comparable between groups (all P > 0.05) including PV and PW characteristics. After 12 months, freedom from AF off antiarrhythmic drug therapy was 51.7% in PVI and 49.7% in PVI+PWI (log-rank P = 0.564). Rapid PW activity was defined as less than the median of the shortest PW cycle length (140 ms) and rapid PV activity was defined as less than the median of the shortest PV cycle length (126 ms). In those with rapid PW activity, the addition of PWI was associated with greater arrhythmia-free survival (56.4%) vs PVI alone (38.6%) (HR: 0.78; 95% CI: 0.67-0.94; log-rank P = 0.030). Moreover, in those undergoing PVI only, the risk of AF recurrence was higher in those with rapid PW activity (55.3% vs 46.5% in slower PW activity; HR: 1.50, 95%CI 1.11-2.26; log-rank P = 0.036). Rapid PV activity and PV cycle length (individual PVs or average of all 4 PVs) were not associated with outcome (all P > 0.05) regardless of ablation strategy. There was no correlation between PW cycle length and posterior low voltage (r = -0.06, P = 0.496). The addition of PWI did not improve arrhythmia-free survival in subgroups with LA enlargement (LA volume index >34 mL/m2) (HR: 0.69; 95% CI: 0.39-1.25; P = 0.301), posterior low-voltage zone (HR: 1.06; 95% CI: 0.68-1.66; P = 0.807), or long-standing PerAF (HR: 1.10; 95% CI: 0.71-1.72; P = 0.669). CONCLUSIONS: Rapid PW activity is associated with an increased risk of AF recurrence post-catheter ablation. The addition of PWI in this subgroup was associated with a significant improvement in freedom from AF compared with PVI alone. The presence of rapid PW activity may identify patients with PerAF likely to benefit from PWI.

The Role of Posterior Wall Isolation in Catheter Ablation for Persistent Atrial Fibrillation and Systolic Heart Failure: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Catheter ablation for patients with atrial fibrillation (AF) and heart failure with reduced ejection fraction (HFrEF) is associated with improved left ventricular ejection fraction (LVEF) and survival compared with medical therapy. Nonrandomized studies have reported improved success with posterior wall isolation (PWI). Objective: To determine the impact of pulmonary vein isolation (PVI) with PWI vs PVI alone on outcomes in patients with HFrEF. Design, Setting, and Participants: This was an ad hoc secondary analysis of the CAPLA trial, a multicenter, prospective, randomized control trial that involved 11 centers in 3 countries (Australia, Canada, and UK). CAPLA featured 338 patients with persistent AF randomized to either PVI plusPWI or PVI alone. This substudy included patients in the original CAPLA study who had symptomatic HFrEF (LVEF <50% and New York Heart Association class ≥II). Interventions: Pulmonary vein isolation with PWI vs PVI alone. Main Outcomes and Measures: The primary end point was freedom from any documented atrial arrhythmia greater than 30 seconds, after a single ablation procedure, without the use of antiarrhythmic drug (AAD) therapy at 12 months. Results: A total of 98 patients with persistent AF and symptomatic HFrEF were identified (mean [SD] age, 62.1 [9.8] years; 79.5% men; and mean [SD] LVEF at baseline, 34.6% [7.9%]). After 12 months, 58.7% of patients with PVI plus PWI were free from recurrent atrial arrhythmia without the use of AAD therapy vs 61.5% with PVI alone (hazard ratio, 1.02; 95% CI, 0.54-1.91; P = .96). There were no significant differences in freedom from atrial arrhythmia with or without AAD therapy after multiple procedures (PVI plus PWI vs PVI alone, 60.9% vs 65.4%; P = .73) or AF burden (median, 0% in both groups; P = .78). Mean LVEF improved substantially in PVI plus PWI (∆ LVEF, 19.3% [13.0%; P < .01) and PVI alone (18.2% [14.1%; P < .01), with no difference between groups (P = .71). Normalization of LV function occurred in 65.2% of patients in the PVI plus PWI group and 50.0% of patients with PVI alone (P = .13). Conclusions and Relevance: The results of this study indicate that addition of PWI to PVI did not improve freedom from arrhythmia recurrence or recovery of LVEF in patients with persistent AF and symptomatic HFrEF. Catheter ablation was associated with significant improvements in systolic function, irrespective of ablation strategy used. These results caution against the routine inclusion of PWI in patients with HFrEF undergoing first-time catheter ablation for persistent AF. Trial Registration: http://anzctr.org.au Identifier: ACTRN12616001436460.

Ventricular Tachycardia and ICD Therapy Burden With Catheter Ablation Versus Escalated Antiarrhythmic Drug Therapy.

BACKGROUND: Catheter ablation improves ventricular tachycardia (VT) event-free (time to event) survival in patients with antiarrhythmic drug (AAD)-refractory VT and previous myocardial infarction (MI). The effects of ablation on recurrent VT and implantable cardioverter-defibrillator (ICD) therapy (burden) have yet to be investigated. OBJECTIVES: This study sought to compare the VT and ICD therapy burden following treatment with either ablation or escalated AAD therapy among patients with VT and previous MI in the VANISH (Ventricular tachycardia AblatioN versus escalated antiarrhythmic drug therapy in ISchemic Heart disease) trial. METHODS: The VANISH trial randomized patients with previous MI and VT despite initial AAD therapy to either escalated AAD treatment or catheter ablation. VT burden was defined as the total number of VT events treated with ≥1 appropriate ICD therapy. Appropriate ICD therapy burden was defined as the total number of appropriate shocks or antitachycardia pacing therapies (ATPs) delivered. The Anderson-Gill recurrent event model was used to compare burden between the treatment arms. RESULTS: Of the 259 enrolled patients (median age, 69.8 years; 7.0% women), 132 patients were randomized to ablation and 129 patients were randomized to escalated AAD therapy. Over 23.4 months of follow-up, ablation-treated patients had a 40% lower shock-treated VT event burden and a 39% lower appropriate shock burden compared with patients who received escalated AAD therapy (P <0.05 for all). A reduction in VT burden, ATP-treated VT event burden, and appropriate ATP burden among ablation patients was only demonstrated in the stratum of patients with amiodarone-refractory VT (P <0.05 for all). CONCLUSIONS: Among patients with AAD-refractory VT and a previous MI, catheter ablation reduced shock-treated VT event burden and appropriate shock burden compared with escalated AAD therapy. There was also lower VT burden, ATP-treated VT event burden, and appropriate ATP burden among ablation-treated patients; however, the effect was limited to patients with amiodarone-refractory VT.

Standard vs Augmented Ablation of Paroxysmal Atrial Fibrillation for Reduction of Atrial Fibrillation Recurrence: The AWARE Randomized Clinical Trial.

Importance: Recurrent atrial fibrillation (AF) commonly occurs after catheter ablation and is associated with patient morbidity and health care costs. Objective: To evaluate the superiority of an augmented double wide-area circumferential ablation (WACA) compared with a standard single WACA in preventing recurrent atrial arrhythmias (AA) (atrial tachycardia, atrial flutter, or atrial fibrillation [AF]) in patients with paroxysmal AF. Design, Setting, and Participants: This was a pragmatic, multicenter, prospective, randomized, open, blinded end point superiority clinical trial conducted at 10 university-affiliated centers in Canada. The trial enrolled patients 18 years and older with symptomatic paroxysmal AF from March 2015 to May 2017. Analysis took place between January and April 2022. Analyses were intention to treat. Interventions: Patients were randomized (1:1) to receive radiofrequency catheter ablation for pulmonary vein isolation with either a standard single WACA or an augmented double WACA. Main Outcomes and Measures: The primary outcome was AA recurrence between 91 and 365 days postablation. Patients underwent 42 days of ambulatory electrocardiography monitoring after ablation. Secondary outcomes included need for repeated catheter ablation and procedural and safety variables. Results: Of 398 patients, 195 were randomized to the single WACA (control) arm (mean [SD] age, 60.6 [9.3] years; 65 [33.3%] female) and 203 to the double WACA (experimental) arm (mean [SD] age, 61.5 [9.3] years; 66 [32.5%] female). Overall, 52 patients (26.7%) in the single WACA arm and 50 patients (24.6%) in the double WACA arm had recurrent AA at 1 year (relative risk, 0.92; 95% CI, 0.66-1.29; P = .64). Twenty patients (10.3%) in the single WACA arm and 15 patients (7.4%) in the double WACA arm underwent repeated catheter ablation (relative risk, 0.72; 95% CI, 0.38-1.36). Adjudicated serious adverse events occurred in 13 patients (6.7%) in the single WACA arm and 14 patients (6.9%) in the double WACA arm. Conclusions and Relevance: In this randomized clinical trial of patients with paroxysmal AF, additional ablation by performing a double ablation lesion set did not result in improved freedom from recurrent AA compared with a standard single ablation set. Trial Registration: ClinicalTrials.gov Identifier: NCT02150902.

Effect of Catheter Ablation Using Pulmonary Vein Isolation With vs Without Posterior Left Atrial Wall Isolation on Atrial Arrhythmia Recurrence in Patients With Persistent Atrial Fibrillation: The CAPLA Randomized Clinical Trial.

Importance: Pulmonary vein isolation (PVI) alone is less effective in patients with persistent atrial fibrillation (AF) compared with paroxysmal AF. The left atrial posterior wall may contribute to maintenance of persistent AF, and posterior wall isolation (PWI) is a common PVI adjunct. However, PWI has not been subjected to randomized comparison. Objective: To compare PVI with PWI vs PVI alone in patients with persistent AF undergoing first-time catheter ablation. Design, Setting, and Participants: Investigator initiated, multicenter, randomized clinical trial involving 11 centers in 3 countries (Australia, Canada, UK). Symptomatic patients with persistent AF were randomized 1:1 to either PVI with PWI or PVI alone. Patients were enrolled July 2018-March 2021, with 1-year follow-up completed March 2022. Interventions: The PVI with PWI group (n = 170) underwent wide antral pulmonary vein isolation followed by posterior wall isolation involving linear ablation at the roof and floor to achieve electrical isolation. The PVI-alone group (n = 168) underwent wide antral pulmonary vein isolation alone. Main Outcomes and Measures: Primary end point was freedom from any documented atrial arrhythmia of more than 30 seconds without antiarrhythmic medication at 12 months, after a single ablation procedure. The 23 secondary outcomes included freedom from atrial arrhythmia with/without antiarrhythmic medication after multiple procedures, freedom from symptomatic AF with/without antiarrhythmic medication after multiple procedures, AF burden between study groups at 12 months, procedural outcomes, and complications. Results: Among 338 patients randomized (median age, 65.6 [IQR, 13.1] years; 76.9% men), 330 (97.6%) completed the study. After 12 months, 89 patients (52.4%) assigned to PVI with PWI were free from recurrent atrial arrhythmia without antiarrhythmic medication after a single procedure, compared with 90 (53.6%) assigned to PVI alone (between-group difference, -1.2%; hazard ratio [HR], 0.99 [95% CI, 0.73-1.36]; P = .98). Of the secondary end points, 9 showed no significant difference, including freedom from atrial arrhythmia with/without antiarrhythmic medication after multiple procedures (58.2% for PVI with PWI vs 60.1% for PVI alone; HR, 1.10 [95% CI, 0.79-1.55]; P = .57), freedom from symptomatic AF with/without antiarrhythmic medication after multiple procedures (68.2% vs 72%; HR, 1.20 [95% CI, 0.80-1.78]; P = .36) or AF burden (0% [IQR, 0%-2.3%] vs 0% [IQR, 0%-2.8%], P = .47). Mean procedural times (142 [SD, 69] vs 121 [SD, 57] minutes, P < .001) and ablation times (34 [SD, 21] vs 28 [SD, 12] minutes, P < .001) were significantly shorter for PVI alone. There were 6 complications for PVI with PWI and 4 for PVI alone. Conclusions and Relevance: In patients undergoing first-time catheter ablation for persistent AF, the addition of PWI to PVI alone did not significantly improve freedom from atrial arrhythmia at 12 months compared with PVI alone. These findings do not support the empirical inclusion of PWI for ablation of persistent AF. Trial Registration: anzctr.org.au Identifier: ACTRN12616001436460.

Antitachycardia pacing success in implantable cardioverter-defibrillators by patient, device, and programming characteristics.

BACKGROUND: Antitachycardia pacing (ATP) is an established implantable cardioverter-defibrillator (ICD) therapy that terminates ventricular tachycardias (VTs) without painful ICD shocks. However, factors influencing ATP success are not well understood. OBJECTIVE: The purpose of this study was to examine ATP success rates by patient, device, and programming characteristics. METHODS: This retrospective analysis of the PainFree SmartShock Technology study included spontaneous ATP-treated monomorphic VT episodes. ATP success rates were calculated for various factors. Also, the relationship of ATP programming on shock burden and syncope were investigated. RESULTS: Of the 2770 enrolled patients (2200 [79%] male; mean age 65 years), 1699 (61%) received an ICD and 1071 (39%) a cardiac resynchronization therapy - defibrillator. ATP had >80% rate of success for terminating VTs overall, with similar rates observed between ICD and cardiac resynchronization therapy - defibrillator devices (82.2% vs 80.3%, respectively; P = .81) as well as between primary and secondary prevention patients with ICDs (77.2% vs 83.9% respectively; P = .25). Arrhythmias with a median cycle length of ≥320 ms had a significantly higher ATP success rate (88.0%; 95% confidence interval 84.8%-90.6%). The cumulative percentage of ATP success increased from 71% at 1 ATP sequence delivered to 87% at ≥8 sequences delivered. Programming more ATP sequences was associated with lower shock burden (P = .0005). There was no evidence that more sequences were associated with higher rates of syncope (P = .16). CONCLUSION: Delivering more ATP sequences resulted in a higher overall success of terminating VTs, while programming more ATP was associated with decreased shock burden and no evidence of increased syncope or acceleration. This suggests that more ATP sequences should be programmed when possible, but confirmation in prospective studies will be necessary.

First Randomized, Multicenter, Placebo-Controlled Study of Self-Administered Intranasal Etripamil for Acute Conversion of Spontaneous Paroxysmal Supraventricular Tachycardia (NODE-301).

BACKGROUND: Pharmacologic termination of paroxysmal supraventricular tachycardia (PSVT) often requires medically supervised intervention. Intranasal etripamil, is an investigational fast-acting, nondihydropyridine, L-type calcium channel blocker, designed for unsupervised self-administration to terminate atrioventricular nodal-dependent PSVT. Phase 2 results showed potential safety and efficacy of etripamil in 104 patients with PSVT. METHODS: NODE-301, a phase 3, multicenter, double-blind, placebo-controlled study evaluated the efficacy and safety of etripamil nasal spray administered, unsupervised in patients with symptomatic sustained PSVT. After a medically supervised etripamil test dose while in sinus rhythm, patients were randomized 2:1 to receive etripamil 70 mg or placebo. When PSVT symptoms developed, patients applied a cardiac monitor and attempted a vagal maneuver; if symptoms persisted, they self-administered blinded treatment. An independent Adjudication Committee reviewed continuous electrocardiogram recordings. The primary efficacy endpoint was termination of adjudicated PSVT within 5 hours after study drug administration. RESULTS: NODE-301 accrued 156 positively adjudicated PSVT events treated with etripamil (n=107) or placebo (n=49). The hazard ratio for the primary endpoint, time-to-conversion to sinus rhythm during the 5-hour observation period, was 1.086 (95% CI, 0.726-1.623; P=0.12). In predefined sensitivity analyses, etripamil effects (compared with placebo) occurred at 3, 5, 10, 20, and 30 minutes (P<0.05). For example, at 30 minutes, there was a 53.7% of SVT conversion in the treatment arm compared to 34.7% in the placebo arm (hazard ratio, 1.87 [95% CI, 1.09-3.22]; P=0.02). Etripamil was well tolerated; adverse events were mainly related to transient nasal discomfort and congestion (19.6% and 8.0%, respectively, of randomized treatment-emergent adverse events. CONCLUSIONS: Although the primary 5-hour efficacy endpoint was not met, analyses at earlier time points indicated an etripamil treatment effect in terminating PSVT. Etripamil self-administration during PSVT was safe and well tolerated. These results support continued clinical development of etripamil nasal spray for self-administration during PSVT in a medically unsupervised setting. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03464019.

Treatment and Prevention of Cardiovascular Implantable Electronic Device (CIED) Infections.

An expanded role for cardiac implantable electronic devices (CIEDs) in recent decades reflects an aging population and broader indications for devices, including both primary prevention and management of dysrhythmias. CIED infection is one of the most important device-related complications and has a major impact on mortality, quality of life, healthcare utilization, and cost. Unfortunately, the investigation and management of CIED infection remain complex, often necessitating complete and timely removal of the device and leads in order to eradicate the infection. In addition, the translation of knowledge from an extensive literature to a disparate group of medical practitioners has often been inadequate. This review of CIED infection management highlights the significant advances made during the past decade, including diagnostic criteria, advanced imaging, and next-generation sequencing for culture-negative cases or those in which uncertainty remains. We also outline the role and indication for powered lead extraction, the process of antibiotic choice and treatment duration, considerations related to the timing and location for reimplantation, and preimplantation risk stratification and associated interventions to reduce the risk of CIED infection.

L'élargissement du rôle des dispositifs électroniques cardiaques implantables (DECI) au cours des dernières décennies reflète le vieillissement de la population et les indications plus vastes des dispositifs, notamment dans la prévention primaire et la prise en charge des dysrythmies. Les infections liées aux DECI sont l'une des plus importantes complications liées aux dispositifs et ont des conséquences majeures sur la mortalité, la qualité de vie, l'utilisation et les coûts des soins de santé. Malheureusement, le dépistage et la prise en charge des infections liées aux DECI demeurent complexes et nécessitent souvent le retrait complet et rapide du dispositif et des sondes en vue d'éradiquer l'infection. De plus, l'application des connaissances issues d'une vaste littérature à un groupe disparate de médecins praticiens a souvent été inadéquate. La présente revue sur la prise en charge des infections liées aux DECI illustre les avancées importantes réalisées au cours de la dernière décennie, notamment les critères diagnostiques, l'imagerie avancée et le séquençage de prochaine génération des cas à culture négative ou de ceux pour lesquels des incertitudes demeurent. Nous avons aussi décrit le rôle et les indications d'extraction des sondes fonctionnelles, le processus du choix des antibiotiques et de la durée du traitement, les considérations relatives au moment et au lieu de la réimplantation, et la stratification du risque en préimplantation et les interventions associées afin de réduire le risque d'infections liées aux DECI.

Novel ventricular tachyarrhythmia detection enhancement detects undertreated life-threatening arrhythmias.

BACKGROUND: Ventricular tachyarrhythmias (VTA) with low and varying signal amplitudes and morphologies may not be successfully identified utilizing traditional implantable cardioverter-defibrillator algorithms. OBJECTIVE: Develop and validate a novel algorithm (VF Therapy Assurance, VFTA) to improve detection and timely delivery of high-voltage therapy (HVT) for these arrhythmias. METHODS: Arrhythmia detection was simulated on recorded VTA electrograms (EGMs) utilizing Abbott's Merlin.net database. EGMs where an HVT occurred only when VFTA was enabled, or where VFTA provided an HVT >30 seconds earlier than without VFTA, were readjudicated with physician review. As VFTA never prevents detection or therapy, EGMs where VFTA did not activate or alter HVT were not adjudicated. RESULTS: Among 564,353 recorded VTA EGMs from 20,000 devices, VFTA altered HVT in 105 EGMs from 67 devices. Physician adjudication determined that 81.9% (86/105) of these EGMs were true undertreated VTA episodes and would have received appropriate HVT with VFTA enabled. Furthermore, 65% of the episodes (56/86) were ventricular fibrillation, were polymorphic, did not self-terminate during the recording window, or were not amenable antitachycardia pacing. Of those, 87.5% (49/56) would not have elicited HVT without VFTA. Overall, VFTA provided new or earlier appropriate HVT in 0.27% (53/20,000) of devices with an increase in inappropriate HVT in 0.07% (14/20,000) devices. CONCLUSION: The VFTA algorithm successfully identifies VTA missed by traditional detection algorithms, owing to undersensed ventricular signals resulting in the rate falling below the programmed detection rate. The use of VFTA increases the likelihood of delivering life-saving HVT.

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.

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.

Performance evaluation of implantable cardioverter-defibrillators with SmartShock technology in patients with inherited arrhythmogenic diseases.

BACKGROUND: Patients with inherited arrhythmogenic diseases (IADs) are often prescribed preventative implantable cardioverter-defibrillators (ICDs) to manage their increased sudden cardiac arrest risk. However, it has been suggested that ICDs in IAD patients may come with additional risk. We aimed to leverage the PainFree SmartShock Technology dataset to compare inappropriate therapies, appropriate therapies, mortality, and complications in patients with and without IAD. METHODS: This retrospective analysis included extracted, physician-adjudicated, arrhythmic episodes from ICD devices. The incidence of arrhythmic events was estimated with the Kaplan-Meier method using the log-rank test. Cox proportional hazards regression was used to estimate hazard ratios (HRs) with their 95% confidence intervals (CIs). RESULTS: Of the 1699 ICD patients, 77 patients (4.5%) had IAD. Incidence of inappropriate shock was similar in both patients with (3.2% at 24 months) and without (3.8% at 24 months) IAD (HR: 0.80, CI: 0.19-3.30, p = 0.76). In a multivariable analysis IAD was not significantly associated with reduced mortality (HR: 0.64, CI: 0.08-4.80, p = 0.66). The rates of complications were numerically lower in patients with IAD vs without (8.8% vs 9.6% at 24 months respectively), but not statistically significant (HR: 0.83, CI: 0.20-3.38, p = 0.79). CONCLUSIONS: IAD patients showed a very low annual rate of inappropriate therapy. This suggests that newer algorithms, such as the SST algorithm, are equally good at identifying and treating life-threatening arrhythmias in patients regardless of whether they have IAD.

Ventricular tachycardia characteristics and outcomes with catheter ablation vs. antiarrhythmic therapy: insights from the VANISH trial.

AIMS: Catheter ablation is superior to escalated antiarrhythmic drugs among patients with ventricular tachycardia (VT) and prior myocardial infarction (MI). However, it is uncertain whether clinical VT characteristics, should influence choice of therapy. The purpose of this study was to evaluate whether presentation with electrical storm and the clinical VT cycle length predicted response to ablation vs. escalated antiarrhythmic therapy. METHODS AND RESULTS: All patients enrolled in the Ventricular Tachycardia Ablation vs. Escalated Antiarrhythmic Drug Therapy in Ischaemic Heart Disease (VANISH) trial were included. The association between VT cycle length and presentation with electrical storm and the primary outcome of death, subsequent VT storm or appropriate ICD shock was evaluated. Among the study population of 259 patients, escalated antiarrhythmic drug therapy had worse outcomes for those presenting with a VT cycle length >400 ms [<150 b.p.m., 89/259, hazard ratio (HR) 1.7 (1.02-3.13)]. This effect was more pronounced among those taking amiodarone at baseline [HR of 2.22 (1.19-4.16)]. Presentation with VT storm (32/259) did not affect the primary outcome between groups. However, those presenting with VT storm on amiodarone had a trend towards worse outcomes with escalated antiarrhythmic therapy [HR 4.31 (0.55-33.93)]. CONCLUSION: The VT cycle length can influence response to either ablation or escalated drug therapy in patients with VT and prior MI. Those with slow VT had improved outcomes with ablation. Patients presenting with electrical storm demonstrated similar outcomes to the overall trial population, with a trend to benefit of catheter ablation, particularly in those on amiodarone.

Comparative effectiveness of ventricular tachycardia ablation vs. escalated antiarrhythmic drug therapy by location of myocardial infarction: a sub-study of the VANISH trial.

AIMS: Complexity of the ventricular tachycardia (VT) substrate and the size and thickness of infarction area border zones differ based on location of myocardial infarctions (MIs). These differences may translate into heterogeneity in the effectiveness of treatments. This study aims to examine the influence of infarct location on the effectiveness of VT ablation in comparison with escalated pharmacological therapy in patients with prior MI and antiarrhythmic drug (AAD)-refractory VT. METHODS AND RESULTS: VANISH trial participants were categorized based on the presence or absence of an inferior MI scar. Inverse probability of treatment weighted Cox models were calculated for each subgroup. Of 259 randomized patients (median age 69.8 years, 7.0% women), 135 had an inferior MI and 124 had a non-inferior MI. Among patients with an inferior MI, no statistically significant difference in the composite primary outcome of all-cause mortality, appropriate implantable cardioverter-defibrillator (ICD) shock, and VT storm was detected between treatment arms [adjusted hazard ratio (aHR) 0.80, 95% confidence interval (CI) 0.51-1.20]. In contrast, patients with non-inferior MIs had a statistically significant reduction in the incidence of the primary outcome with ablation (aHR 0.48, 95% CI 0.27-0.86). In a sensitivity analysis of anterior MI patients (n = 83), a trend towards a reduction in the primary outcome with ablation was detected (aHR 0.50, 95% CI 0.23-1.09). CONCLUSION: The effectiveness of VT ablation versus escalated AADs varies based on the location of the MI. Patients with MI scars located only in non-inferior regions of the ventricles derive greater benefit from VT ablation in comparison to escalation of AADs in reducing VT-related events.