Citations

Abstract Since its introduction in 2002, left atrial appendage closure (LAAC) has rapidly expanded as an alternative to anticoagulation in patients with atrial fibrillation at high risk of stroke. Harmonized processes for data collection, analysis, and reporting in LAAC trials are essential to enhance research quality and improve clinical practice. The Left Atrial Appendage Academic Research Consortium (LAARC) initiative is an independent collaboration of academic research organizations, cardiology and neurology experts, clinical trialists, and regulatory authorities from the USA, Europe, and Asia. The consortium engaged clinical experts, regulators—including the US Food and Drug Administration (FDA), European Notified Bodies, and Japan’s Pharmaceuticals and Medical Devices Agency (PMDA)—and industry leaders to define standardized study elements and endpoints for LAAC trials. Key considerations included alignment with prior Academic Research Consortium initiatives, procedural and mechanistic insights, and clinical relevance. Consensus definitions were proposed for mortality, stroke, bleeding, and device performance, along with composite endpoints for safety and effectiveness. The proposed LAARC consensus definitions aim to standardize endpoint reporting, improve comparability across studies, and support regulatory and clinical trial applications for this evolving therapy through broad dissemination in the peer-reviewed literature.

Introduction: The combination of local impedance (LI), a direct measure of electrical resistance at the catheter tip, and contact force (CF) may facilitate treatment of atrial fibrillation (AF). This trial is designed to examine the safety and effectiveness of a novel RF catheter that allows measurement of both LI and CF. Hypothesis: Demonstrate the safety and effectiveness of a novel radiofrequency catheter with LI and CF for treatment of drug refractory, recurrent, symptomatic Paroxysmal AF (PAF). Methods: NEwTON AF is a multi-center, global, prospective, single arm study. Patients received index treatment for PAF with the study catheter. The present 6-month endpoint analysis was prospectively planned. Results: The study treated 299 patients at 45 sites in North America, Europe, and Asia. Patients were 39.5% female with a mean age of 62yrs (±12), and had a mean LVEF of 59% and an LA diameter of 3.9cm. Procedure time, LA dwell, and fluoroscopy times were 166, 136, and 15 minutes, respectively. High-power short-duration (HSPD, 45-50W) was exclusively used in 210 cases, which had notably shorter procedure times than the 82 cases that used conventional power, 148 vs 208 min, respectively. Acute procedural success was observed in 98.3% of cases. As of 6 months, freedom from documented recurrence of any atrial arrhythmia was 79.9% (Figure). Recurrence in relation to LI shows that pts with a 20Ω LI drop (in at least 60% of lesions) had better 6m outcomes (84.2% vs 73.3, p=0.04). The freedom from safety event rate at 30d was 96.0%; events included pericarditis (6), access complications (2), pulmonary edema (2), embolism (2), cerebrovascular accident (1), tamponade (1). Pericarditis was higher in pts with a history of COVID at enrollment, 16.3% vs 5.9%, p=0.025. Conclusions: This data suggests that patient outcomes and safety for this novel catheter are promising. Further data from this study, including 12m outcomes, and detailed analysis of local impedance data are forthcoming.

Background The PINNACLE FLX (Protection Against Embolism for Non‐valvular AF [Atrial Fibrillation] Patients: Investigational Device Evaluation of the Watchman FLX LAA [Left Atrial Appendage] Closure Technology) trial evaluated the safety and efficacy of a next‐generation left atrial appendage closure device (WATCHMAN FLX; Boston Scientific, Marlborough, MA). At 1 year, the study met the primary end points of safety and anatomical efficacy/appendage closure. This final report of the PINNACLE FLX trial includes the prespecified secondary end point of ischemic stroke or systemic embolism at 2 years, also making it the first report of 2‐year outcomes with this next‐generation left atrial appendage closure device. Methods and Results Patients with nonvalvular atrial fibrillation with CHA 2 DS 2 ‐VASc score ≥2 (men) or ≥3 (women), with an appropriate rationale for left atrial appendage closure, were enrolled to receive the left atrial appendage closure device at 29 US centers. Adverse events were assessed by an independent clinical events committee, and imaging was assessed by independent core laboratories. Among 395 implanted patients (36% women; mean age, 74 years; CHA 2 DS 2 ‐VASc, 4.2±1.5), the secondary efficacy end point of 2‐year ischemic stroke or systemic embolism was met, with an absolute rate of 3.4% (annualized rate, 1.7%) and an upper 1‐sided 95% confidence bound of 5.3%, which was superior to the 8.7% performance goal. Two‐year rates of adverse events were as follows: 9.3% all‐cause mortality, 5.5% cardiovascular death, 3.4% all stroke, and 10.1% major bleeding (Bleeding Academic Research Consortium 3 or 5). There were no additional systemic embolisms, device embolizations, pericardial effusions, or symptomatic device‐related thrombi after 1 year. Conclusions The secondary end point of 2‐year stroke or systemic embolism was met at 3.4%. In these final results of the PINNACLE FLX trial, the next‐generation WATCHMAN FLX device demonstrated favorable safety and efficacy outcomes.

Despite the global COVID-19 pandemic, during the past 2 years, there have been numerous advances in our understanding of arrhythmia mechanisms and diagnosis and in new therapies. We increased our understanding of risk factors and mechanisms of atrial arrhythmias, the prediction of atrial arrhythmias, response to treatment, and outcomes using machine learning and artificial intelligence. There have been new technologies and techniques for atrial fibrillation ablation, including pulsed field ablation. There have been new randomized trials in atrial fibrillation ablation, giving insight about rhythm control, and long-term outcomes. There have been advances in our understanding of treatment of inherited disorders such as catecholaminergic polymorphic ventricular tachycardia. We have gained new insights into the recurrence of ventricular arrhythmias in the setting of various conditions such as myocarditis and inherited cardiomyopathic disorders. Novel computational approaches may help predict occurrence of ventricular arrhythmias and localize arrhythmias to guide ablation. There are further advances in our understanding of noninvasive radiotherapy. We have increased our understanding of the role of His bundle pacing and left bundle branch area pacing to maintain synchronous ventricular activation. There have also been significant advances in the defibrillators, cardiac resynchronization therapy, remote monitoring, and infection prevention. There have been advances in our understanding of the pathways and mechanisms involved in atrial and ventricular arrhythmogenesis.

Abstract Background The MITRAL Trial (Mitral Implantation of TRAnscatheter vaLves) evaluates the safety and feasibility of balloon-expandable aortic transcatheter heart valves in patients with severe mitral valve disease with mitral annular calcification (MAC), failed surgical rings or failed bioprostheses. Purpose We sought to evaluate 4-year outcomes of patients enrolled in the MITRAL trial. Methods This is a prospective study that enrolled 91 high surgical risk patients at 13 sites in the U.S. 30 patients underwent Mitral Valve-in-Valve (MViV), 30 Valve-in-Ring (MViR) and 31 Valve-in-MAC (ViMAC). 4-year outcomes of these patients were evaluated in this analysis. Primary endpoints and key serious adverse events including deaths were adjudicated by an independent Clinical Events Committee. Cardiac computed tomography (CT) and echocardiographic images were evaluated by independent CT and Echocardiographic Core Laboratories. Results Mean age was 74.3±8.9 years. Most patients undergoing MViV and ViMAC were female (MVIV=63.3%, MViR=36.7% and ViMAC=71%). Mean STS score was 9.2±6.6% (MViV 10.2±6.5%, MViR 8.7±4.7%, ViMAC=8.6±8.2%). All-cause mortality at 4 years was higher for ViMAC and MViR: MViV=6.9% (cardiovascular 3.4%), MViR=48.1% (cardiovascular 18.5%), ViMAC=51.9% (cardiovascular 29.6%), p=0.002 (Figure 1). At 4 years, all survivors had ≤1+ mitral regurgitation and most had none or trace mitral regurgitation (MViV=87.5, MViR=33.3% and ViMAC=100%). Mean mitral valve gradients remained stable (MViV=5.9±2.2 mmHg, MViR= 6.6±5.1 mmHg, ViMAC=5.1±1.0 mmHg), Figure 2. Most survivors experienced significant improvement of symptoms and were in NYHA class I-II at 4-year follow-up (MViV=78.9%, MViR=66.7% and ViMAC=66.7%). Conclusions MViV is associated with excellent outcomes at 4 years. MViR and ViMAC were associated with higher mortality at 4 years. However, most survivors in all groups experienced sustained improvement of symptoms and stable THV performance at 4 years. Whether survival bias had an impact on THV performance and improved symptoms at follow-up is not known and deserves further evaluation. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Unrestricted Research Grant from Edwards Lifesciences.

Introduction: Transcatheter mitral valve replacement (TMVR) using aortic transcatheter heart valves (THV) is developing as an alternative to surgery for patients with severely degenerated mitral valve (MV) bioprostheses. Retrospective self-reported registries have collected outcomes on these TMVR procedures in the STS/ACC Transcatheter Valve Therapy Registry and in the Valve-in-Valve International Database. Most reported TMVR procedures for failed surgical bioprostheses have been performed using a transapical access approach. A prospective comprehensive evaluation of mitral Valve-in-Valve (VIV) outcomes, including transseptal access has not previously been conducted. Objectives: To evaluate in-hospital and 30-day clinical outcomes of transseptal mitral VIV with SAPIEN 3 THV in patients with very high surgical risk. Methods: Prospective enrollment of very high surgical risk patients with symptomatic severely degenerated MV surgical bioprostheses in 30 patients at 15 sites in the U.S. Candidates were assessed by a case review committee prior to approval. Baseline qualifying echocardiograms and cardiac CT studies were analyzed by independent core labs. Echocardiograms, cardiac CT studies and neurology evaluations were also performed after mitral VIV procedures. Clinical events were adjudicated by a clinical events committee and safety was monitored by a data safety monitoring board. Results: 26 patients have been enrolled between July 2016 and June 2017. Mean age was 83 years, 62% female, mean STS score was 10% and 62% were in New York Heart Association class III or IV. Transseptal access was used in all procedures. Technical success was achieved in all patients and there was no in-hospital mortality. There was no 30-day cardiovascular mortality and 4% (1 patient) 30-day all-cause mortality (1 patient died of asphyxia on day 29 after choking on pills at home), which was lower than the 30-day mortality in the TVT registry (9%). Detailed procedural, in-hospital and 30-day outcomes will be presented on the complete cohort of 30 patients. Conclusions: In patients without surgical alternatives, transseptal mitral ViV procedures in failed surgical bioprostheses are associated with high technical and procedural success and low 30-day mortality.

Introduction: Transcatheter mitral valve replacement (TMVR) using aortic transcatheter heart valves (THV) is developing as an alternative to surgery for patients with severe mitral valve disease due to degenerated mitral bioprostheses or failed surgical rings who are poor surgical candidates. Outcomes of off-label procedures in the United States are being collected in the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy (STS/ACC TVT) Registry. A comprehensive analysis of mitral Valve-in-Valve (VIV) versus Valve-in-Ring (VIR) outcomes has not previously been performed. Objectives: To evaluate in-hospital and 30-day clinical outcomes of mitral VIV and VIR procedures in the United States. Methods: Retrospective analysis of data from the STS/ACC TVT Registry on patients who underwent mitral VIV or VIR procedures. Results: 587 patients underwent TMVR VIV (n=494) or VIR (n=93) procedures between January 2013 and December 2016 at 144 hospitals. Median age was 76 (VIV) and 73 (VIR) years, (p=0.024), 60.9% (VIV) and 44.1% (VIR) were female (p=0.003), median left ventricular ejection fraction was 55% in VIV and 50% in VIR (p <0.001), and median STS score was 10.5% (VIV) and 9.2% (VIR), p=0.131. Transseptal access was utilized in 35% VIV and 46.2% VIR procedures, p=0.081. Procedural success was achieved in 74.4% of VIV and 57.8%VIR (p=0.239). Left ventricular outflow tract (LVOT) obstruction was more common in VIR (5.4%) vs VIV (0.06%), p=0.003. Post-procedure median mean mitral valve gradient was 4mmHg in both groups. 95.7% of VIV and 86% of VIR patients had post-procedure mitral regurgitation ≤1(+), p<0.001. In-hospital mortality was 6.9% for VIV and 9.7% for VIR (p=0.343). 30-day mortality was 9% for VIV and 12% for VIR (p=0.387). At 30-day follow up, 85.6% of VIV and 77.7% of VIR patients were in New York Heart Association class I or II (p=0.398). Conclusions: TMVR VIV and VIR using aortic transcatheter heart valves in high surgical risk patients are associated with similar in-hospital and 30-day mortality and symptom benefit. LVOT obstruction post-TMVR and residual mitral regurgitation ≥2 (+) were more frequent in VIR procedures. The long-term effect of these procedures is not known and requires further evaluation.