Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes Afford New Opportunities in Inherited Cardiovascular Disease Modeling

Fundamental studies of molecular and cellular mechanisms of cardiovascular disease pathogenesis are required to create more effective and safer methods of their therapy. The studies can be carried out only when model systems that fully recapitulate pathological phenotype seen in patients are used. Application of laboratory animals for cardiovascular disease modeling is limited because of physiological differences with humans. Since discovery of induced pluripotency generating induced pluripotent stem cells has become a breakthrough technology in human disease modeling. In this review, we discuss a progress that has been made in modeling inherited arrhythmias and cardiomyopathies, studying molecular mechanisms of the diseases, and searching for and testing drug compounds using patient-specific induced pluripotent stem cell-derived cardiomyocytes

Efficacy and safety of left atrial appendage closure with WATCHMAN in patients with or without contraindication to oral anticoagulation: 1-Year follow-up outcome data of the EWOLUTION trial

Background Left atrial appendage (LAA) occlusion with WATCHMAN has emerged as viable alternative to vitamin K antagonists in randomized controlled trials. Objective EWOLUTION was designed to provide data in routine practice from a prospective multicenter registry. Methods A total of 1025 patients scheduled for a WATCHMAN implant were prospectively and sequentially enrolled at 47 centers. Indication for LAA closure was based on European Society of Cardiology guidelines. Follow-up and transesophageal echocardiography (TEE) were performed per local practice. Results The baseline CHA 2 DS 2 -VASc score was 4.5 ± 1.6; the mean age was 73.4 ± 9 years; previous transient ischemic attack/ischemic stroke was present in 312 (30.5%), 155 (15.1%) had previous hemorrhagic stroke, and 320 (31.3%) had a history of major bleeding; and 750 (73%) were deemed unsuitable for oral anticoagulation therapy. WATCHMAN implant succeeded in 1005 (98.5%) of patients, without leaks >5 mm in 1002 (99.7%) with at least 1 TEE follow-up in 875 patients (87%). Antiplatelet therapy was used in 784 (83%), while vitamin K antagonists were used in only 75 (8%). At 1 year, mortality was 98 (9.8%), reflecting the advanced age and comorbidities in this population. Device thrombus was observed in 28 patients at routine TEE (3.7%) and was not correlated with the drug regimen ( P = .14). Ischemic stroke rate was 1.1% (relative risk 84% vs estimated historical data); the major bleeding rate was 2.6% and was predominantly (2.3%) nonprocedure/device related. Conclusion LAA closure with the WATCHMAN device has a high implant and sealing success. This method of stroke risk reduction appears to be safe and effective with an ischemic stroke rate as low as 1.1%, even though 73% of patients had a contraindication to and were not using oral anticoagulation

Incidence and predictors of 2-year mortality following percutaneous left atrial appendage occlusion in the EWOLUTION trial

Aims: Sufficient survival time following left atrial appendage occlusion (LAAO) is essential for ensuring the efficacy and cost-effectiveness of this strategy for stroke prevention. Understanding prognostic factors for early mortality after LAAO could optimize patient selection. In the current study, we perform an in-depth analysis of 2-year mortality after LAAO, focusing particularly on potential predictors. Methods and results: The EWOLUTION registry is a real-world cohort comprising 1020 patients that underwent LAAO. Endpoint definitions were pre-specified, and death was categorized as cardiovascular, non-cardiovascular, or unknown origin. Mortality rates were calculated from Kaplan–Meier estimates. Baseline characteristics significantly associated with death in univariate Cox regression analysis were incorporated into the multivariate analysis. All multivariate predictors were included in a risk model. Two-year mortality rate was 16.4% [confidence interval (CI): 14.0–18.7%], with 50% of patients dying from a non-cardiovascular cause. Multivariate baseline predictors of 2-year mortality included age [hazard ratio (HR) 1.05, CI: 1.03–1.08, per year increase], heart failure (HR 1.73, CI: 1.24–2.41), vascular disease (HR 1.47, CI: 1.05–2.05), valvular disease (HR 1.63, CI: 1.15–2.33), abnormal liver function (HR 1.80, CI: 1.02–3.17), and abnormal renal function (HR 1.58, CI: 1.10–2.27). Mortality rate exhibited a gradual rise as the number of risk factors increased, reaching 46.1% in patients presenting with five or six risk factors. Conclusion: One in six patients died within 2 years after LAAO. We identified six independent predictors of mortality. When combined, this model showed a gradual increase in mortality rate with a growing number of risk factors, which may guide appropriate patient selection for LAAO. Clinical trial registration: The original EWOLUTION registry was registered at clinicaltrials.gov under identifier NCT01972282

Combining Watchman left atrial appendage closure and catheter ablation for atrial fibrillation: Multicentre registry results of feasibility and safety during implant and 30 days follow-up

Aims Long-term results from catheter ablation therapy for atrial fibrillation (AF) remain uncertain and clinical practice guidelines recommend continuation of long-term oral anticoagulation in patients with a high stroke risk. Left atrial appendage closure (LAAC) with Watchman has emerged as an alternative to long-term anticoagulation for patients accepting of the procedural risks. We report on the initial results of combining catheter ablation procedures for AF and LAAC in a multicentre registry. Methods and results Data were pooled from two prospective, real-world Watchman LAAC registries running in parallel in Europe/Middle-East/Russia (EWOLUTION) and Asia/Australia (WASP) between 2013 and 2015. Of the 1140 patients, 139 subjects at 10 centres underwent a concomitant AF ablation and LAAC procedure. The mean CHA 2 DS 2 -VASc score was 3.4 ± 1.4 and HAS-BLED score 1.5 ± 0.9. Successful Watchman implantation was achieved in 100% of patients. The overall 30-day serious adverse event (SAE) rate was 8.7%, with the device and/or procedure-related SAE rate of 1.4%. One pericardial effusion required percutaneous drainage, but there were no strokes, device embolization, or deaths at 30 days. The 30-day bleeding SAE rate was 2.9% with 55% of patients prescribed NOAC and 38% taking warfarin post-procedure. Conclusion The outcomes from these international, multicentre registries support the feasibility and safety of performing combined procedures of ablation and Watchman LAAC for patients with non-valvular AF and high stroke risk. Further data are needed on long-term outcomes for the hybrid technique on all-cause stroke and mortality

2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation: executive summary.

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withdrawn 2017 hrs ehra ecas aphrs solaece expert consensus statement on catheter and surgical ablation of atrial fibrillation

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