Citations

Abstract Background and Aims Stroke and systemic embolism are recognized but poorly characterized complications of atrial fibrillation (AF) and left atrial flutter (AFL) catheter ablation. Their incidence, outcomes, and procedural associations remain insufficiently defined. Methods Retrospective global registry was initiated by the European Heart Rhythm Association Scientific Committee. A secure database captured data from ablation centres worldwide on general AF and left AFL ablation activity, as well as detailed information on patients with symptomatic embolic events between 2017 and 2024. Results Overall, 204 centres reported 335 743 ablation procedures and 550 embolic events (incidence 0.16%). Centre-level rate ranged from 0% to 3.1%. Most events were cerebral (94%), followed by peripheral (5%), and combined (1%). Coronary air embolism accounted for 62% of all peripheral events. Intraprocedural events occurred in 93 patients (17%), within 72 h in 357 (78%) and beyond 72 h in 100 (22%); 128 cases (23%) were diagnosed after hospital discharge. Nonparoxysmal AF (0.23% vs 0.15%; P < .001), centre experience, and ablation energy source (radiofrequency, 0.16%; cryoballoon, 0.16%; pulsed field ablation, 0.25%; laserballoon, 0.88%; P < .001) were associated with embolic risk. Median NIHSS score after stroke was 4 (interquartile range, 2–9). Three-month follow-up was available for 518 patients with embolism (95%): 181 (35%) had sequelae and 16 (3%) died. Conclusions Symptomatic embolic events are infrequent but associated with significant morbidity and mortality. Most events occur early, though a substantial proportion arise later. Higher event rates were observed with laser and possibly with pulsed field ablation. A greater centre experience was associated with a lower embolism incidence.

ABSTRACT Background This exploratory analysis of the NEURO‐TTRansform Phase 3 trial evaluated the efficacy of eplontersen in patients with hereditary transthyretin (ATTRv) amyloidosis with polyneuropathy by genetic variant. Methods Changes from baseline in NEURO‐TTRansform primary endpoints serum transthyretin (TTR) at Week 65, modified Neuropathy Impairment Score+7 (mNIS+7) composite score, and Norfolk Quality of Life‐Diabetic Neuropathy (Norfolk QoL‐DN) total score at Week 66 were evaluated in patients with early‐onset (aged < 50 years) and late‐onset (aged ≥ 50 years) Val30Met (p.Val50Met) or non‐Val30Met ATTRv amyloidosis with polyneuropathy. Secondary endpoints from NEURO‐TTRansform were also evaluated by genetic variant. Results In total, 144 patients with early‐onset ( n = 54) or late‐onset ( n = 31) Val30Met or non‐Val30Met ( n = 59), ATTRv amyloidosis with polyneuropathy were randomized to eplontersen. A further 60 patients from NEURO‐TTR with early‐onset ( n = 16) or late‐onset ( n = 17) Val30Met or non‐Val30Met ( n = 27), served as a historical placebo group. The mean percentage difference (95% confidence interval) in serum TTR was −79.9 (−87.8, −72.0), −85.0 (−93.3, −76.6), and −70.6 (−77.7, −63.5) with eplontersen versus placebo in the early‐ and late‐onset Val30Met, and non‐Val30Met groups, respectively. Across subgroups, the change from baseline to Week 66 in mNIS+7 composite score was generally well maintained, and the Norfolk QoL‐DN total score improved with eplontersen versus worsening with placebo. The Polyneuropathy Disability score was maintained in most patients. From baseline to Week 65, the modified body mass index was maintained with eplontersen compared to a marked reduction (worsening) for placebo. Conclusions Findings were suggestive of consistent benefits in reducing neuropathy impairment and improving QoL with eplontersen versus historical placebo, across TTR variants. Trial Registration ClinicalTrials.gov: NCT04136184, NCT01737398

Importance There is a lack of long-term efficacy and safety data on hereditary transthyretin amyloidosis with polyneuropathy (hATTR-PN) and on RNA interference (RNAi) therapeutics in general. This study presents the longest-term data to date on patisiran for hATTR-PN. Objective To present the long-term efficacy and safety of patisiran in adults with hATTR-PN. Design, Setting, and Participants This global open-label extension (OLE) of the APOLLO randomized clinical trial and phase 2 OLE study enrolled patients from 43 hospitals or clinical centers across 19 countries between July 2015 and August 2017, with follow-up until November 2022. Of 212 eligible patients with hATTR who completed the phase 3 APOLLO or phase 2 OLE parent studies, 211 enrolled in and 138 completed the global OLE. Intervention Patisiran, 0.3 mg/kg, intravenously once every 3 weeks for up to 5 years. Main Outcomes and Measures Outcomes evaluated at year 5 of the global OLE included disability (polyneuropathy disability [PND] score); polyneuropathy severity (Neuropathy Impairment Score [NIS]), nutritional status (modified body mass index [mBMI]), quality of life (Norfolk Quality of Life–Diabetic Neuropathy [Norfolk QOL-DN]), and Rasch-Built Overall Disability Scale (R-ODS), with no statistical hierarchy. Safety, survival probability, and mortality were also assessed. Results At the global OLE baseline, the mean (SD) age was 61.3 (12.3) years, and 156 patients (73.9%) were male. In 138 patients completing the study, PND scores remained stable or improved in 89 patients (65.0%), NISs showed a mean (SD) change of 10.9 (14.7), and mean (SD) mBMI (calculated as weight in kilograms divided by height in meters squared times serum albumin in grams per liter) increased by 46.4 (120.7) over 5 years from baseline. Norfolk QOL-DN and R-ODS scores showed mean (SD) changes of 4.1 (16.7) and –3.7 (6.2), respectively. Adverse events (AEs) leading to study withdrawal occurred in 47 patients (22.3%). Infusion-related reactions were the most common treatment-related AE (n = 34 [16.1%]). Overall, 41 patients (19.4%) died during the study. Patisiran treatment in the parent study and low familial amyloid polyneuropathy score at parent study baseline were associated with significantly improved survival. Conclusions and Relevance In the longest study of an RNAi therapeutic for any disease, patisiran treatment resulted in modest changes for patients with hATTR-PN with an acceptable safety profile. These results highlight the importance of initiating early treatment for hATTR and the potential of RNAi therapeutics in medicine. Trial Registration ClinicalTrials.gov Identifier: NCT02510261

Abstract OBJECTIVES Safety, efficacy and durability are important considerations when selecting a bioprosthesis for aortic valve replacement (AVR). This study assessed 7-year clinical outcomes and haemodynamic performance of the Avalus bioprosthesis. METHODS Patients indicated for surgical AVR were enrolled in this prospective, nonrandomized trial, conducted across 39 sites globally. The primary end-point of this analysis was freedom from surgical explant or percutaneous valve-in-valve reintervention due to structural valve deterioration (SVD) at 7 years of follow-up, determined using Kaplan–Meier (KM) analysis. We also evaluated a composite end-point of SVD and/or severe haemodynamic dysfunction requiring reintervention. Survival, valve-related safety events and haemodynamic performance were assessed. Deaths and safety events were adjudicated by an independent clinical events committee. RESULTS A total of 1132 patients underwent surgical AVR. Mean age was 70 years; 854 patients (75%) were men. The mean STS risk of mortality was 2.0 ± 1.4%, and 659 patients (58%) had a New York Heart Association classification of I/II. One or more concomitant procedures were performed in 577 patients (51%). At 7 years, the Kaplan–Meier rate of freedom from SVD/severe haemodynamic dysfunction requiring reintervention was 1.2% (0.5–2.5%) with no cases adjudicated as SVD. The survival rate was 82.6% (79.5–85.0%). The KM event rate was 5.7% (4.3–7.7%) for reintervention, 6.3% (4.9–8.3%) for endocarditis and 0.4% (0.1–1.1%) for valve thrombosis. Mean aortic gradient, dimensionless velocity index and effective orifice area were 13.8 ± 5.9 mmHg, 0.42 ± 0.09 and 1.99 ± 0.53 cm2, respectively. CONCLUSIONS This analysis demonstrated excellent durability of the Avalus valve with good clinical outcomes and stable haemodynamic performance through 7 years of follow-up.