Laurence D. Sterns

Background: Clinical burden of remote monitoring (RM) in cardiac implantable electronic devices (CIEDs) is high, yet uptake is variable. A digital health platform (VIRTUES) is posited to fill these gaps, with acceptable safety, efficacy and lower costs. Methods: VIRTUES-PM (V-PM) and VIRTUES-ICD (V-ICD) were multicenter, open-label, randomized controlled trials with blinded endpoint adjudication conducted in 13 Canadian centers for V-PM and 11 Canadian centers for V-ICD for patients with RM-eligible CIEDs. Allocation was 1:1 to standard of care (SOC) or VIRTUES care. In V-PM, there were two objectives: demonstration of non-inferiority of safety (time to major adverse cardiac or device-related hospitalizations) and superiority in cost; the secondary outcome was efficacy (time from clinical event to decision). In V-ICD, the first co-primary outcomes were safety and efficacy; cost was considered a second primary outcome. Analysis in each study used a sequential strategy of non-inferiority of the primary outcome, followed by superiority in cost. Outcome assessment was performed by blinded adjudication. Results: Between May 29, 2020 and February 28, 2025, 848 participants were randomized in V-PM (n=428 VIRTUES; n=420 SOC) and 1115 in V-ICD (n=526 VIRTUES; n=553 SOC). The mean age was 70±12 years; 34% were women in V-PM, and 65±12 years, 22% were women in V-ICD. Over a follow-up of 18 months, the safety outcome in V-PM occurred in 26 participants (6.1%) in the VIRTUES care arm, compared to 31 (7.4%) in SOC; hazard ratio 0.83; 95% CI (0.49, 1.39); p for non-inferiority=0.0213. Cost was lower by -$77 97% CI(-$100, -$54), p<0.01. In V-ICD, the safety outcome occurred in 62 (11.0%) in VIRTUES, and 62 (11.2%) in SOC, hazard ratio 0.98, 95% CI (0.69,1.39); p for non-inferiority 0.007. Efficacy was also non-inferior with time from clinical events to decision: median 2.0 interquartile range (0 to 15) in the VIRTUES care arm vs 1.00 IQR (0 to 8) days in the SOC arm (p =0.003 for non-inferiority). The second primary outcome of cost per participant was significantly lower in the VIRTUES care arm as compared with SOC (mean adjusted cost difference/participant -C$77; 95% CI (-$105, -$49); p<0.01. Conclusion: VIRTUES care was non-inferior to SOC for safety in patients with PMs and ICDs, as well as in efficacy in ICDs. In both trials, significant cost-savings were found. These two trials support the use of this technology for comprehensive CIED management. Trial Registration: VIRTUES PM NCT03636230 first posted August 17, 2018, VIRTUES ICD NCT03405740 first posted January 23, 2018.

Background: Pulmonary vein isolations (PVI) are being performed using a high-power, short duration (HPSD) strategy. The purpose of this study was to compare the clinical efficacy and safety outcomes of a HPSD vs low-power long duration (LPLD) approach to PVI in patients with paroxysmal atrial fibrillation (AF). Methods: Patients were grouped according to a HPSD (≥40 W) or LPLD (≤ 35 W) strategy. The primary endpoint was the one-year recurrence of any atrial arrhythmia lasting ≥ 30 seconds, detected using three 14-day ambulatory continuous ECG monitoring. Procedural and safety endpoints were also evaluated. The primary analysis were regression models incorporating propensity scores yielding adjusted relative risk (RR _a ) and mean difference (MD _a ) estimates. Results: Of the 398 patients included in the AWARE Trial, 173 (43%) underwent HPSD and 225 (57%) LPLD ablation. The distribution of power was 50 W in 75%, 45 W in 20% and 40 W in 5% in the HPSD group, and 35W with 25W on the posterior wall in the LPLD group. The primary outcome was not statistically significant at 30.1% vs 22.2% in HPSD and LPLD group with RR _a 0.77 (95% confidence interval [CI]) 0.55-1.10; p=0.165). The secondary outcome of repeat catheter ablation was not statistically significant at 6.9% and 9.8% (RR _a 1.59 [95% CI 0.77-3.30]; p=0.208) respectively. The incidence of any ECG documented AF during the blanking period was numerically lower in the HPSD group: 1.7% vs 8.0% (RR _a 3.95 [95% CI 1.00-15.61; p=0.049). The total procedure time was significantly shorter in the HPSD group (MD _a 97.5 minutes [95% CI 84.8-110.4)]; p<0.0001) with no difference in adjudicated serious adverse events. Conclusions: A HPSD strategy was associated with significantly shorter procedural times with similar efficacy in terms of clinical arrhythmia recurrence. Importantly, there was no signal for increased harm with a HPSD strategy. Graphical Non-standard Abbreviations and Acronyms: HPSD: High-Power Short Duration; LPLD: Low-Power Long Duration; QOL: Quality of Life; WACA: wide area circumferential ablation; PVI: Pulmonary Vein Isolation; AF: Atrial Fibrillation Clinical Perspective: What is known: -The optimal power and duration of ablation lesions to produce durable pulmonary vein isolation remain unclear. -Nonrandomized studies have suggested clinical efficacy with high-power short duration radiofrequency ablation vs low-power long duration. What this study adds: -In this large substudy of the AWARE Trial, a high-power short duration radiofrequency ablation strategy was found to be similarly effective as a low-power long duration strategy with no difference in time to first recurrence of any AF lasting ≥ 30 seconds. -Procedural were substantially reduced with high-power short duration ablation with no significant difference in overall complication rates.

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 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.

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. 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). 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.

Aims: Cardiac implantable electronic devices with device advisories have the potential of device malfunction. Remote monitoring (RM) of devices has been suggested to allow the identification of abnormal device performance and permit early intervention. We sought to describe the outcomes of patients with and without RM in devices subject to the Abbott Premature Battery Depletion (PBD) advisory with data from a Canadian registry. Methods and results: Patients with an Abbott device subject to the PBD advisory from nine implantable cardioverter defibrillator (ICD) implanting centres in Canada were included in the registry. The use of RM was identified from baseline and follow-up data in the registry. The primary outcome was detection of PBD and all-cause mortality. A total of 2666 patients were identified with a device subject to the advisory. In all, 1687 patients (63.2%) had RM at baseline. There were 487 deaths during follow-up. At a mean follow-up of 5.7 ± 0.7 years, mortality was higher in those without a remote monitor compared with RM at baseline (24.7% vs. 14.5%; P < 0.001). Pre-mature battery depletion was identified in 36 patients (2.1%) with RM vs. 7 (0.7%) without RM (P = 0.004). Time to battery replacement was significantly reduced in patients on RM (median 5 vs. 13 days, P = 0.001). Conclusion: The use of RM in patients with ICD and cardiac resynchronization therapy under advisory improved detection of PBD, time to device replacement, and was associated with a reduction in all-cause mortality. The factors influencing the association with mortality are unknown and deserve further study.