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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., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Objectives: Atrioventricular (AV) conduction disturbances are still common following transcatheter aortic valve replacement (TAVR). The study evaluates the feasibility and clinical effect of self-expanding (SE)-TAVR employing an optimized cusp-overlay technique (COT) at 1 year in a German all-comers population., Methods: We analyzed 1-year clinical outcomes in patients who received a SE valve employing the optimized COT. Consecutive patients who underwent SE-TAVR (EvolutR, EvolutPRO) after introduction of the COT as the default implantation technique in 2020 were included (n = 101). Consecutive TAVR patients from the same operators using the conventional implantation technique (CIT) served as the control group (n = 116)., Results: The COT was successfully performed in more than 80% of the patients in the COT group. (81.2%, n = 82/101). At discharge, no difference regarding AV block of at least II (CIT 19.47% vs COT 21%; P = .86) and permanent pacemaker (PPM) implantation (CIT 17.5% vs COT 19%; P = .73) was observed between the cohorts. New left bundle branch block (LBBB) was significantly less frequent in the COT group (CIT 40.71% vs COT 26%; P = .029). Paravalvular leakage (PVL) greater than I° was reduced in the COT cohort (CIT 8.62% vs COT 0.99%; P = .012). There was no significant difference in mortality (CIT 18.27% vs COT 13.83%; P = .44), stroke (CIT 9.62% vs COT 15.96%; P = .16) or cardiovascular rehospitalization after 1 year (CIT 25.96% vs 24.47%; P = .92) between the groups., Conclusions: Implementation of COT-TAVR was feasible and safe, and it resulted in an improvement of TAVR outcomes regarding PVL greater than I° and new onset LBBB. However, with respect to PPM, no difference was observed 1-year post-TAVR.

Background: Left atrial appendage occlusion (LAAO) provides mechanical cardioembolic protection for atrial fibrillation (AF) patients who cannot use oral anticoagulation therapy (OAT). Patients with a thrombotic event despite OAT are at high risk for recurrence and may also benefit from LAAO., Objectives: This study sought to investigate the efficacy of LAAO in AF patients with a thrombotic event on OAT compared to: 1) LAAO in AF patients with a contraindication for OAT; and 2) historical data., Methods: The international LAAO after stroke despite oral anticoagulation (STR-OAC LAAO) collaboration included patients who underwent LAAO because of thrombotic events on OAT. This cohort underwent propensity score matching and was compared to the EWOLUTION (Evaluating Real-Life Clinical Outcomes in Atrial Fibrillation Patients Receiving the WATCHMAN Left Atrial Appendage Closure Technology) registry, which represents patients who underwent LAAO because of OAT contraindications. The primary outcome was ischemic stroke. Event rates were compared between cohorts and with historical data without OAT, yielding relative risk reductions based on risk scores., Results: Analysis of 438 matched pairs revealed no significant difference in the ischemic stroke rate between the STR-OAC LAAO and EWOLUTION cohorts (2.5% vs 1.9%; HR: 1.37; 95% CI: 0.72-2.61). STR-OAC LAAO patients exhibited a higher thromboembolic risk (HR: 1.71; 95% CI: 1.04-2.83) but lower bleeding risk (HR: 0.39; 95% CI: 0.18-0.88) compared to EWOLUTION patients. The mortality rate was slightly higher in EWOLUTION (4.3% vs 6.9%; log-rank P = 0.028). Relative risk reductions for ischemic stroke were 70% and 78% in STR-OAC LAAO and EWOLUTION, respectively, compared to historical data without OAT., Conclusions: LAAO in patients with a thrombotic event on OAT demonstrated comparable stroke rates to the OAT contraindicated population in EWOLUTION. The thromboembolic event rate was higher and the bleeding rate lower, reflecting the intrinsically different risk profile of both populations. Until randomized trials are available, LAAO may be considered in patients with an ischemic event on OAT., Competing Interests: Funding Support and Author Disclosures Dr Maarse has received an educational grant from Boston Scientific. Dr Tondo serves on the advisory board of Boston Scientific; and has received lecture and tutoring fees from Boston Scientific and Abbott Medical. Dr Demkow has received proctoring fees from Boston Scientific and Abbott. Dr de Backer has received institutional research grants and consulting fees from Abbott and Boston Scientific. Dr Nielsen-Kudsk has received grants from Abbott and Boston Scientific. Dr Estevez-Loureiro is a proctor for Abbott Vascular, Boston Scientific, and Lifetech. Dr de Prado is a proctor for Boston Scientific. Dr Nombela-Franco is a proctor for Abbott Vascular, Edwards Lifesciences, and Boston Scientific. Dr Salinas is a proctor for Abbott Vascular. Dr Berti is a proctor for Edwards Lifesciences, Boston Scientific, and Abbott. Dr Millan has received consultant fees/honoraria from Abbott Laboratories and Boston Scientific. Dr Arzamendi has received consultant fees/honoraria from Abbott Laboratories and Boston Scientific. Dr Agarwal is a member of the Speaker Bureau and proctor for Medtronics, Abbott, Edwards Lifesciences, and Boston Scientific. Dr Spoon is a speaker for Medtronic, Abiomed, and Abbott. Dr El-Chami is a consultant for Medtronic and Boston Scientific. Dr Adamo has received speaker honoraria from Abbott Structural Heart. Dr van Dijk is a proctor for Boston Scientific. Dr Swaans is a proctor/lecturer for Abbott Vacular, Bioventrix Inc, Boston Scientific, Cardiac Dimensions, Edwards Lifesciences, GE Healthcare, and Philips Healthcare. Dr Vireca is an employee of Boston Scientific. Dr Bergmann has received speaker honoraria from Boston Scientific and Abbott; and has received research support from Boston Scientific and Abbott. Dr Boersma is a consultant for Boston Scientific; and is a proctor for Abbott. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Scarce data exist on the evolution of device-related thrombus (DRT) after left atrial appendage closure (LAAC)., Objectives: This study sought to assess the incidence, predictors, and clinical impact of persistent and recurrent DRT in LAAC recipients., Methods: Data were obtained from an international multicenter registry including 237 patients diagnosed with DRT after LAAC. Of these, 214 patients with a subsequent imaging examination after the initial diagnosis of DRT were included. Unfavorable evolution of DRT was defined as either persisting or recurrent DRT., Results: DRT resolved in 153 (71.5%) cases and persisted in 61 (28.5%) cases. Larger DRT size (OR per 1-mm increase: 1.08; 95% CI: 1.02-1.15; P = 0.009) and female (OR: 2.44; 95% CI: 1.12-5.26; P = 0.02) were independently associated with persistent DRT. After DRT resolution, 82 (53.6%) of 153 patients had repeated device imaging, with 14 (17.1%) cases diagnosed with recurrent DRT. Overall, 75 (35.0%) patients had unfavorable evolution of DRT, and the sole predictor was average thrombus size at initial diagnosis (OR per 1-mm increase: 1.09; 95% CI: 1.03-1.16; P = 0.003), with an optimal cutoff size of 7 mm (OR: 2.51; 95% CI: 1.39-4.52; P = 0.002). Unfavorable evolution of DRT was associated with a higher rate of thromboembolic events compared with resolved DRT (26.7% vs 15.1%; HR: 2.13; 95% CI: 1.15-3.94; P = 0.02)., Conclusions: About one-third of DRT events had an unfavorable evolution (either persisting or recurring), with a larger initial thrombus size (particularly >7 mm) portending an increased risk. Unfavorable evolution of DRT was associated with a 2-fold higher risk of thromboembolic events compared with resolved DRT., Competing Interests: Funding Support and Author Disclosures Dr Rodés-Cabau holds the Research Chair “Fondation Famille Jacques Larivière” for the Development of Structural Heart Disease Interventions (Laval University, Quebec City, Canada). He also has received institutional research grants from Boston Scientific. Dr Maarse has received an unrestricted grant from Boston Scientific. Dr Pérez de Prado has served as a proctor for Boston Scientific. Dr Gupta has served as a proctor for Abbott. Dr Sanchez has served as a speaker and proctor for Boston Scientific. Dr Wang has served as a consultant for Edwards Lifesciences, Boston Scientific, and Neochord; and received research grant support from Boston Scientific assigned to his employer, the Henry Ford Health System. Dr Demkow has served as a proctor for Abbott and Boston Scientific. Dr Alkhouli has served as a consultant for Boston Scientific. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

The most common arrhythmia, atrial fibrillation (AF), increases with age and is associated with a 5-fold increased risk of stroke. Although lifelong oral anticoagulation (OAC) is strongly recommended for stroke prevention in patients with AF and CHA 2 DS 2 -VASc ≥ 2 only 50-60% of patients in Western countries belonging to this group are treated with oral anticoagulants, and less than half of these adhere to therapy over time. Before 2010, the numerous limitations associated with vitamin K antagonists (VKAs) were considered to be the reason behind OAC underuse; however, the approval of direct oral anticoagulants (DOACs) that require once- or twice-daily intake, no regular blood tests and fewer drug-food interactions has resulted in only modest improvements in OAC use and adherence.

Background: With the emergence of new subvariants, the disease severity of Severe Acute Respiratory Syndrome Coronavirus-2 has attenuated. This study aimed to compare the disease severity in patients hospitalized with omicron variant infection to those with influenza infection., Methods: We compared data from the multicenter observational, prospective, epidemiological "CORONA Germany" (Clinical Outcome and Risk in hospitalized COVID-19 patients) study on patients infected with Severe Acute Respiratory Syndrome Coronavirus-2 to retrospective data on influenza infection cases from November 2016 to August 2022. Severe Acute Respiratory Syndrome Coronavirus-2 cases were classified as wild-type/delta variant before January 2022, or omicron variant from January 2022 onward. The primary outcome was in-hospital mortality, adjusted for age, gender, and comorbidities., Results: The study included 35,806 patients from 53 hospitals in Germany, including 4,916 patients (13.7%) with influenza infection, 16,654 patients (46.5%) with wild-type/delta variant infection, and 14,236 patients (39.8%) with omicron variant infection. In-hospital mortality was highest in patients with wild-type/delta variant infection (16.8%), followed by patients with omicron variant infection (8.4%) and patients with influenza infection (4.7%). In the adjusted analysis, higher age was the strongest predictor for in-hospital mortality (age 80 years vs. age 50 years: OR 4.25, 95% CI 3.10-5.83). Both, patients with wild-type/delta variant infection (OR 3.54, 95% CI 3.02-4.15) and patients with omicron variant infection (OR 1.56, 95% CI 1.32-1.84) had a higher risk for in-hospital mortality than patients with influenza infection., Conclusion: After adjusting for age, gender and comorbidities, patients with wild-type/delta variant infection had the highest risk for in-hospital mortality compared to patients with influenza infection. Even for patients with omicron variant infection, the adjusted risk for in-hospital mortality was higher than for patients with influenza infection. The adjusted risk for in-hospital mortality showed a strong age dependency across all virus types and variants., Trial Registration Number: NCT04659187., Competing Interests: NG reports grants from Boston Scientific, grants from Medtronic and support from Bayer Vital outside the submitted work. MAG reports grants/speaker honoraria and consultation fees from Boston Scientific, Farapulse Inc., Biosense Webster, Abbott and Medtronic outside the submitted work. WG reports grants/speaker honoraria and consultation fees from AstraZeneca, Olympus and PulmonX outside the submitted work. This does not alter our adherence to PLOS ONE policies on sharing data and materials. All other authors have nothing to disclose., (Copyright: © 2023 Dickow et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Women with atrial fibrillation (AF) generally experience worse symptoms, poorer quality of life, and have a higher risk of stroke and death. There is limited availability of sex-related differences regarding left atrial appendage occlusion (LAAO)., Aims: The aim of this study was to evaluate the sex-related differences in patients undergoing LAAO in EWOLUTION., Methods: A total of 1025 patients scheduled for elective LAAO therapy employing the WATCHMAN Gen 2.5 prospectively consented for participation; 1005 patients received a successful implant and were followed for 2 years. As we detected sex-related differences in baseline data we performed a propensity score matching. The primary endpoint is a combined endpoint of survival free from mortality, major bleeding, ischemic stroke, transitory ischemic attack (TIA) and systemic embolization (SE) up to 2-year clinical follow-up. Secondary Endpoints were periprocedural data and overall 2-year survival., Results: Women were older but had less often vascular disease and hemorrhagic stroke. There was no sex-related significant difference after LAAO at 2 years in the combined endpoint of survival free from mortality, major bleeding, ischemic stroke, TIA, and SE (female vs. male: 79% vs.76%, p = 0.24) or in overall survival (female vs. male: 85% vs. 82%, p = 0.16). Procedural data showed a higher sealing rate after the implantation in women (complete sealing female 94% vs. male 90%, p = 0.033), significantly more pericardial effusions (female 1.2% vs. male 0.2%, p = 0.031) and a similar periprocedural risk profile., Conclusions: Females undergoing LAAO differ in various baseline variables, but after adjustment, we observed similar safety and efficacy of LAAO with no significant difference in long-term outcomes between women and men., (© 2023 The Authors. Catheterization and Cardiovascular Interventions published by Wiley Periodicals LLC.)

Aims: We aim to assess the theoretical impact of the atrial flow regulator (AFR) on survival in heart failure., Methods and Results: The prospective, multicentre, open-label, non-randomised PRELIEVE study (NCT03030274) assessed the safety and efficacy of the Occlutech AFR device in patients with symptomatic heart failure with reduced ejection fraction (HFrEF) (left ventricular ejection fraction (LVEF) ≥ 15% and <40%) or heart failure with preserved ejection fraction (HFpEF) (LVEF ≥40% and <70%) and elevated PCWP (≥15 mmHg at rest or ≥25 mmHg during exercise). In this analysis, after the first 60 patients completed 12 months of follow-up, the theoretical impact of AFR implantation on survival was assessed by comparing the observed mortality rate with the median predicted probability for one-year mortality. Each subject's risk of mortality was predicted from individual baseline data using the Meta-Analysis Global Group in Chronic HF (MAGGIC) prognostic model. A total of 87 patients (46% female, median age 69 years [IQR 62-74]) had undergone successful device implantation for the treatment of HFrEF (53%) and HFpEF (47%). Sixty patients had a complete 12 month follow-up. The median follow-up was 351 days (interquartile range [IQR] 202-370). Six (7%) patients died during follow-up (8.6 deaths per 100 patient-years; 95% confidence interval [CI] 2.7 to 15.5), all of which had HFrEF. The median predicted mortality rate for the overall study population was 12.2 deaths per 100 patient-years (95% CI 10.2 to 14.7). While the observed mortality rate (0 deaths per 100 patient-years) was significantly lower than the median predicted mortality rate (9.3 deaths per 100 patient-years; 95% CI 8.4 to 11.1) in patients with HFpEF (-9.3 deaths per 100 patient-years; 95% CI -11.1 to -8.4), there was no difference in patients with HFrEF (-3.6 deaths per 100 patient-years; 95% CI -9.5 to 3.0). Four deaths were HF-related deaths (5.7 HF-related deaths per 100 patient-years; 95% CI 1.4 to 11.9; 10.8 HF-related deaths per 100 patient-years; 95% CI 2.5 to 23.1 in the HFrEF subgroup)., Conclusions: In patients with HFpEF, the mortality rate following AFR implantation was lower than the predicted mortality rate. Dedicated randomised, controlled trials are needed - and currently ongoing - to investigate whether the AFR improves mortality., (© 2023 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Aims: The aim of the SCIENCE trial was to investigate whether a single treatment with direct intramyocardial injections of adipose tissue-derived mesenchymal stromal cells (CSCC&#95;ASCs) was safe and improved cardiac function in patients with chronic ischaemic heart failure with reduced ejection fraction (HFrEF)., Methods and Results: The study was a European multicentre, double-blind, placebo-controlled phase II trial using allogeneic CSCC&#95;ASCs from healthy donors or placebo (2:1 randomization). Main inclusion criteria were New York Heart Association (NYHA) class II-III, left ventricular ejection fraction (LVEF) <45%, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels >300 pg/ml. CSCC&#95;ASCs or placebo (isotonic saline) were injected directly into viable myocardium. The primary endpoint was change in left ventricular end-systolic volume (LVESV) at 6-month follow-up measured by echocardiography. A total of 133 symptomatic HFrEF patients were included. The treatment was safe without any drug-related severe adverse events or difference in cardiac-related adverse events during a 3-year follow-up period. There were no significant differences between groups during follow-up in LVESV (0.3 ± 5.0 ml, p = 0.945), nor in secondary endpoints of left ventricular end-diastolic volume (-2.0 ± 6.0 ml, p = 0.736) and LVEF (-1.6 ± 1.0%, p = 0.119). The NYHA class improved slightly within the first year in both groups without any difference between groups. There were no changes in 6-min walk test, NT-proBNP, C-reactive protein or quality of life the first year in any groups., Conclusion: The SCIENCE trial demonstrated safety of intramyocardial allogeneic CSCC&#95;ASC therapy in patients with chronic HFrEF. However, it was not possible to improve the pre-defined endpoints and induce restoration of cardiac function or clinical symptoms., (© 2023 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Left atrial appendage closure (LAAC) has emerged as an alternative to oral anticoagulation (OAC) for stroke prevention in patients with atrial fibrillation (AF). OAC treatment has been proven feasible in mild-to-moderate chronic kidney disease (CKD). In contrast, the optimal antithrombotic management of AF patients with end-stage renal disease (ESRD) is unknown and LAAC has not been proven in these patients in prospective randomized clinical trials., Objectives: The objective of this study is to evaluate safety and efficacy of LAAC in patients with ESRD., Methods: Patients undergoing LAAC were collected in a German multicenter real-world observational registry. A composite endpoint consisting of the occurrence of ischemic stroke/transient ischemic attack, systemic embolism, and/or major clinical bleeding was assessed. Patients with ESRD were compared with propensity score-matched patients without severe CKD. ESRD was defined as a glomerular filtration rate < 15 ml/min/1.73 m 2 or chronic hemodialysis treatment., Results: A total of 604 patients were analyzed, including 57 with ESRD and 57 propensity-matched patients. Overall, 596 endocardial and 8 epicardial LAAC procedures were performed. Frequency of major complications was 7.0% (42/604 patients) in the overall cohort, 8.8% (5/57 patients) in patients with ESRD, and 10.5% (6/57 patients) in matched controls (p = 0.75). The estimated event-free survival of the combined endpoint after 500 days was 90.7 ± 4.5% in patients with ESRD and 90.2 ± 5.5% in matched controls (p = 0.33)., Conclusions: LAAC had comparable procedural safety and clinical efficacy in patients with ESRD and patients without severe CKD., (© 2023 The Authors. Catheterization and Cardiovascular Interventions published by Wiley Periodicals LLC.)

Background: The new-generation WATCHMAN FLX (Boston Scientific) device for left atrial appendage occlusion has been modified in various aspects to improve procedural results. No comparison of the WATCHMAN FLX device with the previous WATCHMAN device is available., Objective: We aimed to compare procedural results with WATCHMAN FLX in patients on dual antiplatelet therapy at ∼3 months with data with WATCHMAN (EWOLUTION [Registry on WATCHMAN Outcomes in Real-Life Utilization])., Methods: One hundred sixty-four consecutive patients receiving the WATCHMAN FLX device in 4 European centers were included in the retrospective ALSTER-FLX registry. As a control group for a matched-pair analysis, 1020 patients treated with the WATCHMAN device and data up to first follow-up (∼3 months) from EWOLUTION were used., Results: Implantation was successful in all ALSTER-FLX patients (100%) and similar to results in EWOLUTION (99%) (P = .2). We observed no stroke or device embolization in ALSTER-FLX similar to EWOLUTION (stroke 0.5%, device embolization 0.4%) at 3 months. Numerically less ALSTER-FLX patients (2.4%) developed a device-associated thrombus as compared with 3.7% EWOLUTION patients, yet without reaching statistical significance after matching (median [95% confidence interval] device-associated thrombus pairwise event difference 2 [0-6]; P = .1). WATCHMAN FLX implantation was associated with a significant higher sealing rate compared with EWOLUTION at 3 months (ALSTER-FLX 90% vs EWOLUTION 79.4%; P = .039 after matching). Major nonprocedural bleeding events and mortality were similar after matching (median event difference for bleeding 0 [-3 to 3]; P = .6 and death 1 [-2 to 4]; P = .3)., Conclusion: Periprocedural, early 3-month outcomes with WATCHMAN FLX demonstrate a similar safety profile and an improved sealing rate compared to the WATCHMAN device., (Copyright © 2022 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: In REDUCE LAP-HF II (A Study to Evaluate the Corvia Medical, Inc IASD System II to Reduce Elevated Left Atrial Pressure in Patients With Heart Failure), implantation of an atrial shunt device did not provide overall clinical benefit for patients with heart failure with preserved or mildly reduced ejection fraction. However, prespecified analyses identified differences in response in subgroups defined by pulmonary artery systolic pressure during submaximal exercise, right atrial volume, and sex. Shunt implantation reduces left atrial pressures but increases pulmonary blood flow, which may be poorly tolerated in patients with pulmonary vascular disease (PVD). On the basis of these results, we hypothesized that patients with latent PVD, defined as elevated pulmonary vascular resistance during exercise, might be harmed by shunt implantation, and conversely that patients without PVD might benefit., Methods: REDUCE LAP-HF II enrolled 626 patients with heart failure, ejection fraction ≥40%, exercise pulmonary capillary wedge pressure ≥25 mm Hg, and resting pulmonary vascular resistance <3.5 Wood units who were randomized 1:1 to atrial shunt device or sham control. The primary outcome-a hierarchical composite of cardiovascular death, nonfatal ischemic stroke, recurrent HF events, and change in health status-was analyzed using the win ratio. Latent PVD was defined as pulmonary vascular resistance ≥1.74 Wood units (highest tertile) at peak exercise, measured before randomization., Results: Compared with patients without PVD (n=382), those with latent PVD (n=188) were older, had more atrial fibrillation and right heart dysfunction, and were more likely to have elevated left atrial pressure at rest. Shunt treatment was associated with worse outcomes in patients with PVD (win ratio, 0.60 [95% CI, 0.42, 0.86]; P =0.005) and signal of clinical benefit in patients without PVD (win ratio, 1.31 [95% CI, 1.02, 1.68]; P =0.038). Patients with larger right atrial volumes and men had worse outcomes with the device and both groups were more likely to have pacemakers, heart failure with mildly reduced ejection fraction, and increased left atrial volume. For patients without latent PVD or pacemaker (n=313; 50% of randomized patients), shunt treatment resulted in more robust signal of clinical benefit (win ratio, 1.51 [95% CI, 1.14, 2.00]; P =0.004)., Conclusions: In patients with heart failure with preserved or mildly reduced ejection fraction, the presence of latent PVD uncovered by invasive hemodynamic exercise testing identifies patients who may worsen with atrial shunt therapy, whereas those without latent PVD may benefit.

Background: Left atrial appendage occlusion (LAAO) is recommended for patients with atrial fibrillation at increased stroke risk, where effective long-term oral anticoagulation (OAC) is not feasible. In order to assess long-term safety of LAAO with aspirin monotherapy or no therapy, we aimed to report on patients with the Watchman LAAO device (Boston Scientific) once postimplantation intensified antiplatelet or anticoagulation therapy is discontinued., Methods: A total of 1025 patients scheduled for elective LAAO therapy prospectively consented for participation in the EWOLUTION registry; 1005 patients received a successful implant and were followed for 2 years. We identified 766 patients in EWOLUTION on single-antiplatelet therapy (SAPT; n = 639) or no therapy (n = 127) for ≥1 year following LAAO., Results: Three to 6 months after LAAO, 766 patients were switched to SAPT or no therapy and were followed for at least 1 year until the study's conclusion or with events while on SAPT/ no therapy; mean time on SAPT/no therapy was 536.56 ± 177.59 days. Patients experienced 1.4 ischemic strokes per 100 patient years (PY) despite a CHA2DS2-VASC score of 4.3 ± 1.6. Major nonprocedural bleeding rates were low, with 1.3 major bleeds per 100 PY with a mean HAS-BLED score of 2.2 ± 1.2. Furthermore, the ischemic stroke rate in the SAPT/no-therapy subgroup was similar to the whole EWOLUTION collective and high-risk subgroups; the bleeding rate was even lower. When analyzed separately, strokes (2.1/100 PY) and bleedings (1.4/100 PY) of the no-therapy subgroup were similar to patients on SAPT (strokes 0.7/100 PY [P=.70]; bleedings 1.4/100 PY [P=.90])., Conclusions: Outcome data of patients on SAPT/no therapy for ≥1 year following Watchman implantation in the EWOLUTION registry suggest the efficacy and safety of LAAO.

Background: Acute myocardial injury (AMJ), assessed by elevated levels of cardiac troponin, is associated with fatal outcome in coronavirus disease 2019 (COVID-19). However, the role of acute cardiovascular (CV) events defined by clinical manifestation rather than sole elevations of biomarkers is unclear in hospitalized COVID-19 patients., Objective: The aim of this study was to investigate acute clinically manifest CV events in hospitalized COVID-19 patients., Methods: From 1 March 2020 to 5 January 2021, we conducted a multicenter, prospective, epidemiological cohort study at six hospitals from Hamburg, Germany (a portion of the state-wide 45-center CORONA Germany cohort study) enrolling all hospitalized COVID-19 patients. Primary endpoint was occurrence of a clinically manifest CV-event., Results: In total, 132 CV-events occurred in 92 of 414 (22.2%) patients in the Hamburg-cohort: cardiogenic shock in 10 (2.4%), cardiopulmonary resuscitation in 12 (2.9%), acute coronary syndrome in 11 (2.7%), de-novo arrhythmia in 31 (7.5%), acute heart-failure in 43 (10.3%), myocarditis in 2 (0.5%), pulmonary-embolism in 11 (2.7%), thrombosis in 9 (2.2%) and stroke in 3 (0.7%). In the Hamburg-cohort, mortality was 46% (42/92) for patients with a CV-event and 33% (27/83) for patients with only AMJ without CV-event (OR 1.7, CI: (0.94-3.2), p = 0.077). Mortality was higher in patients with CV-events (Odds ratio(OR): 4.8, 95%-confidence-interval(CI): [2.9-8]). Age (OR 1.1, CI: (0.66-1.86)), atrial fibrillation (AF) on baseline-ECG (OR 3.4, CI: (1.74-6.8)), systolic blood-pressure (OR 0.7, CI: (0.53-0.96)), potassium (OR 1.3, CI: (0.99-1.73)) and C-reactive-protein (1.4, CI (1.04-1.76)) were associated with CV-events., Conclusion: Hospitalized COVID-19 patients with clinical manifestation of acute cardiovascular events show an almost five-fold increased mortality. In this regard, the emergence of arrhythmias is a major determinant.

Background: Device-related thrombus (DRT) has been considered an Achilles' heel of left atrial appendage occlusion (LAAO). However, data on DRT prediction remain limited., Objectives: This study constructed a DRT registry via a multicenter collaboration aimed to assess outcomes and predictors of DRT., Methods: Thirty-seven international centers contributed LAAO cases with and without DRT (device-matched and temporally related to the DRT cases). This study described the management patterns and mid-term outcomes of DRT and assessed patient and procedural predictors of DRT., Results: A total of 711 patients (237 with and 474 without DRT) were included. Follow-up duration was similar in the DRT and no-DRT groups, median 1.8 years (interquartile range: 0.9-3.0 years) versus 1.6 years (interquartile range: 1.0-2.9 years), respectively (P = 0.76). DRTs were detected between days 0 to 45, 45 to 180, 180 to 365, and >365 in 24.9%, 38.8%, 16.0%, and 20.3% of patients. DRT presence was associated with a higher risk of the composite endpoint of death, ischemic stroke, or systemic embolization (HR: 2.37; 95% CI, 1.58-3.56; P < 0.001) driven by ischemic stroke (HR: 3.49; 95% CI: 1.35-9.00; P = 0.01). At last known follow-up, 25.3% of patients had DRT. Discharge medications after LAAO did not have an impact on DRT. Multivariable analysis identified 5 DRT risk factors: hypercoagulability disorder (odds ratio [OR]: 17.50; 95% CI: 3.39-90.45), pericardial effusion (OR: 13.45; 95% CI: 1.46-123.52), renal insufficiency (OR: 4.02; 95% CI: 1.22-13.25), implantation depth >10 mm from the pulmonary vein limbus (OR: 2.41; 95% CI: 1.57-3.69), and non-paroxysmal atrial fibrillation (OR: 1.90; 95% CI: 1.22-2.97). Following conversion to risk factor points, patients with ≥2 risk points for DRT had a 2.1-fold increased risk of DRT compared with those without any risk factors., Conclusions: DRT after LAAO is associated with ischemic events. Patient- and procedure-specific factors are associated with the risk of DRT and may aid in risk stratification of patients referred for LAAO., Competing Interests: Funding Support and Author Disclosures Dr Maarse has received an unrestricted grant from Boston Scientific. Dr Pérez de Prado has served as a proctor for Boston Scientific. Dr Gupta has served as a proctor for Abbott. Dr Sanchez has served as a speaker and proctor for Boston Scientific. Dr Demkow has served as a proctor for Abbott and Boston Scientific. Dr Alkhouli has served as a consultant for Boston Scientific. Dr Wang has been a consultant for Edwards LifeSciences, Boston Scientific, and Neochord; and has received research grant support from Boston Scientific assigned to employer Henry Ford health system. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: Both balloon-expandable and self-expanding transcatheter aortic valves are used for transcatheter aortic valve implantation (TAVI). We compared procedural and clinical outcome variables of Sapien 3 and Evolut R/Pro in an all-comers collective., Methods: In this single-center registry, patients were consecutively treated with the Sapien 3 from November 2014 to March 2017 (n = 129) and from April 2017 to December 2018 mainly (>95%) with the Evolut R/Pro (n = 124), due to a switch in the main TAVI supplier driven by hospital management. Data were retrospectively analyzed before and after the switch., Results: One-year follow-up data were available for 122 (94%) of the Sapien and 112 (90%) of the Evolut patients. Baseline characteristics were comparable (EuroSCORE: Sapien 21.8 ± 0.9% vs Evolut 22.5 ± 0.8%; P=.20). Evolut implantation was associated with a higher radiation dose (Sapien 35770 ± 2345 mGy•cm² vs Evolut 85072 ± 8202 mGy•cm²; P<.001), more postimplantation balloon dilations (Sapien 17.1% vs Evolut 37.1%; P<.001), but similar procedure time (Sapien 75.2 ± 3.8 min vs Evolut 74.6 ± 3 min; P=.30). In-hospital mortality (Sapien 3.1% vs Evolut 4.0%; P=.70), all-cause mortality (Sapien 13.2% vs Evolut 15.3%; P=.70), all-stroke rate (Sapien 1.5% vs Evolut 6.5%; P=.05), and pacemaker implantation rate (Sapien 13.2% vs Evolut 18.5%; P=.30) were similar at 1 year. Permanent pacemaker rate was numerically higher in the first 6 months with Evolut (<6 months 26.7% vs >6 months 16%; P=.62); furthermore, radiation dose and balloon dilations also suggest a learning curve with Evolut., Conclusions: Switching from Sapien 3 to Evolut R/Pro was not associated with a difference regarding periprocedural or 1-year clinical outcomes.

Aims: Attenuating exercise-induced elevated left atrial pressure with an atrial shunt device is under clinical investigation for treatment of symptomatic heart failure (HF)., Methods and Results: PRELIEVE was a prospective, non-randomised, multicentre, first-in-man study in symptomatic HF patients with reduced (HFrEF) or preserved (HFpEF) ejection fraction and pulmonary capillary wedge pressure (PCWP) ≥15 mmHg at rest or ≥25 mmHg during exercise. Here, we provide follow-up data up to 1 year after implantation of the Atrial Flow Regulator (AFR) device. The AFR was successfully implanted in 53 patients (HFrEF n = 24 and HFpEF n = 29). Two patients were not enrolled due to an unsuccessful transseptal puncture. There was one device embolisation into the left atrium, which required surgical removal. One patient experienced a serious procedure-related adverse event (post-procedural bleeding and syncope). All patients with sufficient echocardiography readout confirmed device patency with left-right shunt both at 3 (n = 47/51, 92%) and 12 (n = 45/49, 92%) months. At 3 months, rest PCWP decreased by 5 (-12, 0) mmHg (P = 0.0003, median Q1, Q3). No patient developed a stroke, worsening of right heart function or significant increase of pulmonary artery pressure. Six (6/53, 11%) patients were hospitalised for worsening of HF and three (3/53, 6%) patients died. We observed improvements in New York Heart Association functional class, 6-min walking distance and quality of life (Kansas City Cardiomyopathy Questionnaire) in certain patients., Conclusions: Implantation of the AFR device in HF patients was feasible. No shunt occlusion, stroke or new right HF was observed during the 1-year follow-up, with clinical improvements in certain patients., (© 2021 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Aims: The diagnostic approach to idiopathic giant-cell myocarditis (IGCM) is based on identifying various patterns of inflammatory cell infiltration and multinucleated giant cells (GCs) in histologic sections taken from endomyocardial biopsies (EMBs). The sampling error for detecting focally located GCs by histopathology is high, however. The aim of this study was to demonstrate the feasibility of gene profiling as a new diagnostic method in clinical practice, namely in a large cohort of patients suffering from acute cardiac decompensation. Methods and Results : In this retrospective multicenter study, EMBs taken from n = 427 patients with clinically acute cardiac decompensation and suspected acute myocarditis were screened (mean age: 47.03 ± 15.69 years). In each patient, the EMBs were analyzed on the basis of histology, immunohistology, molecular virology, and gene-expression profiling. Out of the total of n = 427 patient samples examined, GCs could be detected in 26 cases (6.1%) by histology. An established myocardial gene profile consisting of 27 genes was revealed; this was narrowed down to a specified profile of five genes ( CPT1, CCL20, CCR5, CCR6, TLR8 ) which serve to identify histologically proven IGCM with high specificity in 25 of the 26 patients (96.2%). Once this newly established profiling approach was applied to the remaining patient samples, an additional n = 31 patients (7.3%) could be identified as having IGCM without any histologic proof of myocardial GCs. In a subgroup analysis, patients diagnosed with IGCM using this gene profiling respond in a similar fashion to immunosuppressive therapy as patients diagnosed with IGCM by conventional histology alone. Conclusions : Myocardial gene-expression profiling is a promising new method in clinical practice, one which can predict IGCM even in the absence of any direct histologic proof of GCs in EMB sections. Gene profiling is of great clinical relevance in terms of a) overcoming the sampling error associated with purely histologic examinations and b) monitoring the effectiveness of therapy., Competing Interests: None declared.

Aims: Evidence regarding post-procedural antithrombotic regimen other than used in randomized trials assessing percutaneous left atrial appendage (LAA) closure is limited. The present work aimed to compare different antithrombotic strategies applied in the real-world EWOLUTION study., Methods and Results: A total of 998 patients with successful WATCHMAN implantation were available for the present analysis. The composite ischaemic endpoint of stroke, transitory ischaemic attack, systemic embolism and device thrombus, and the bleeding endpoint defined as at least major bleeding were assessed during an initial period (from implant until first medication change) and long-term period (from first change up to 2 years). The antithrombotic medication chosen in the initial phase was dual antiplatelet therapy (DAPT) in 60%, oral anticoagulation (OAC) in 27%, single antiplatelet therapy (SAPT) in 7%, and no medication in 6%. In the second long-term phase, SAPT was used in 65%, DAPT in 23%, no therapy in 8%, and OAC in 4%. No significant differences were found between the groups regarding the ischaemic endpoint both in the initial period (Kaplan-Meier estimated rate 2.9% for DAPT vs. 4.3% for OAC vs. 3.9% for SAPT or no therapy) and in the second period (4.2% for SAPT vs. 1.8% for DAPT vs. 3.5% for no therapy). With respect to bleeding events, the only difference was found in the initial phase with a higher incidence in patients under SAPT or no therapy., Conclusions: Tailored antithrombotic treatment using even very reduced strategies such as SAPT or no therapy showed no significant differences regarding ischaemic complications after LAA closure., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Aims: Reducing elevated left atrial pressure with an atrial septum shunt device is a possible treatment option in symptomatic heart failure patients. This study aimed to investigate the safety and feasibility of the Atrial Flow Regulator (AFR) in heart failure patients., Methods and Results: AFR-PRELIEVE is a prospective, non-randomised, open-label, multicentre study in patients with symptomatic heart failure NYHA Class III or IV and pulmonary capillary wedge pressure (PCWP) ≥15 mmHg at rest or ≥25 mmHg at exercise irrespective of left ventricular ejection fraction (EF ≥15%). Here we report on procedural and three-month follow-up data for a total of thirty-six enrolled patients. Sixteen (44.5%) patients with reduced EF (HFrEF: EF 15-39%) and twenty (55.5%) patients with preserved EF (HFpEF: EF ≥40%) were enrolled. Implantation success rate and device patency with left-right shunt was 100% (post procedure and at three months) in both patient groups, with one SADE in the HFpEF group which completely resolved. Three (3/36, 8.3%) patients were hospitalised for worsening of heart failure (two HFrEF patients, one HFpEF patient). Individual patients from both the HFrEF and HFpEF groups showed improvement in symptoms and surrogate parameters of heart failure (NYHA class, six-minute walking distance, Kansas City Cardiomyopathy Questionnaire, PCWP, NT-proBNP)., Conclusions: Implantation of the AFR device in heart failure patients is feasible and safe; shunt patency at three months was confirmed in the study. The atrial shunt improved symptoms and surrogate parameters of heart failure in some but not all patients in both the HFpEF and HFrEF groups.

Aims: Ischaemic heart failure (IHF) patients have a poor prognosis even with current guideline-derived therapy. Intramyocardial injections of autologous or allogeneic mesenchymal stromal cells might improve cardiac function leading to better clinical outcome., Methods: The SCIENCE (Stem Cell therapy in IschEmic Non-treatable Cardiac diseasE) consortium has initiated a Horizon 2020 funded multicentre phase II study in six European countries. It is a double-blind, placebo-controlled trial testing the safety and efficacy of allogeneic Cardiology Stem Cell Centre Adipose-derived Stromal Cells (CSCC&#95;ASC) from healthy donors or placebo in 138 symptomatic IHF patients. Main inclusion criteria are New York Heart Association class II-III, left ventricular ejection fraction < 45% and N-terminal pro-B-type natriuretic peptide levels > 300 pg/mL. Patients are randomized in a 2:1 pattern to receive intramyocardial injections of either CSCC&#95;ASC or placebo. CSCC&#95;ASC and placebo treatments are prepared centralized at Rigshospitalet in 5 mL vials as an off-the-shelf product. Vials are distributed to all clinical partners and stored in nitrogen vapour tanks ready to be used directly after thawing. A total of 100 × 10 6 CSCC&#95;ASC or placebo are injected directly into viable myocardium in the infarct border zone using the NOGA XP system (BDS, Cordis, Johnson & Johnson, USA). Primary endpoint is a centralized core-laboratory assessed change in left ventricular end-systolic volume at 6-month follow-up measured by echocardiography. The trial started in January 2017, 58 patients were included and treated until July 2018., Conclusion: The SCIENCE trial will provide clinical data on efficacy and safety of intramyocardial cell therapy of allogeneic adipose-derived stromal cells from healthy donors in patients with IHF., (© 2019 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Objectives: In this propensity-matched analysis of post-left atrial appendage closure antithrombotic therapy, the safety and effectiveness of oral anticoagulation (OAC) and antiplatelet therapy (APT) were compared., Background: Left atrial appendage closure with the WATCHMAN device is an alternative to OAC in patients with nonvalvular atrial fibrillation, who are at high bleeding risk. Initial trials included 45 days of post-implantation OAC, but registry data suggest that APT may suffice., Methods: Patients from the PROTECT-AF (Watchman Left Atrial Appendage System for Embolic Protection in Patients With Atrial Fibrillation), PREVAIL (Watchman LAA Closure Device in Patients With Atrial Fibrillation Versus Long Term Warfarin Therapy), CAP (Continued Access to PROTECT-AF), CAP2 (Continued Access to PREVAIL), ASAP (ASA Plavix Feasibility Study With Watchman Left Atrial Appendage Closure Technology), and EWOLUTION (Registry on WATCHMAN Outcomes in Real-Life Utilization) trials receiving either OAC or APT post-implantation were matched and compared for nonprocedural bleeding and stroke or systemic thromboembolism over 6 months following implantation. Each patient on APT was matched with 2 patients on OAC, with propensity scores derived from age, sex, congestive heart failure, hypertension, diabetes, prior transient ischemic attack or stroke, peripheral vascular disease, left ventricular ejection fraction, renal impairment, and different atrial fibrillation subtypes., Results: The cohort on OAC (n = 1,018; 95% receiving warfarin and 5% receiving nonwarfarin OAC) was prescribed 45-day OAC post-implantation (92% also received single APT), followed by 6-month single or dual APT. The cohort on APT (n = 509; 91% receiving dual APT and 9% receiving single APT) received APT for variable durations. Six-month freedom from nonprocedural major bleeding was similar (OAC, 95.7%; APT, 95.5%; p = 0.775) despite more early bleeds with OAC. Freedom from thromboembolism beyond 7 days was similar between groups (OAC, 98.8%; APT, 99.4%; p = 0.089). However, device-related thrombosis was more frequent with APT (OAC, 1.4%; APT, 3.1%; p = 0.018)., Conclusions: After left atrial appendage closure with the WATCHMAN, although device-related thrombosis was more common with APT, both APT and OAC strategies resulted in similar safety and efficacy endpoints., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Left atrial appendage occlusion with WATCHMAN has emerged as viable alternative to vitamin K antagonists in randomized controlled trials. Evaluating real-life clinical outcomes in atrial fibrillation patients receiving the WATCHMAN left atrial appendage closure technology was designed to collect prospective multicenter outcomes of thromboembolic events, bleeding, and mortality for patients implanted with a WATCHMAN in routine daily practice., Methods: One thousand twenty patients with a WATCHMAN implant procedure were prospectively followed in 47 centers. Left atrial appendage occlusion indication was based on the European Society of Cardiology guidelines. Follow-up and imaging were performed per local practice up to a median follow-up of 2 years., Results: Included population was old (age 73.4±8.9 years), at high risk for stroke (311 prior ischemic stroke/transient ischemic attack and 153 prior hemorrhagic stroke) and bleeding (318 prior major bleeding), with CHA 2 DS 2 -VASc score ≥5 in 49%, hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, Labile international normalized ratio, elderly, drugs/alcohol concomitantly ≥3 in 40% and oral anticoagulation contraindication in 72%. During follow-up, 161 patients (16.4%) died, 22 strokes were observed (1.3/100 patient-years, 83% reduction versus historic data), and 47 major nonprocedural bleeding events (2.7/100 patient-years, 46% reduction versus historic data). Stroke and bleeding rates were consistently lower than historic data in those with prior ischemic (-76% and -41%) or hemorrhagic (-81% and 67%) stroke and prior bleeding (-85% and -30%). Lowest bleeding rates were seen in patients with early discontinuation of dual antiplatelet therapy. Patients with early discontinuation of antithrombotic therapy showed lower bleeding rates, while they were highest for those with prior bleeding. Device thrombus was observed in 34 patients (4.1%) and was not correlated to drug regimen during follow-up ( P=0.28)., Conclusions: During the complete 2-year follow-up of Evaluating Real-Life Clinical Outcomes in Atrial Fibrillation Patients Receiving the WATCHMAN Left Atrial Appendage Closure Technology, patients with a WATCHMAN left atrial appendage occlusion device had consistently low rates of stroke and nonprocedural bleeding, although most were contraindicated to oral anticoagulation and used only single antiplatelet therapy or nothing., Clinical Trial Registration: URL: https://clinicaltrials.gov . Unique identifier: NCT01972282.

Background: Percutaneous mechanical circulatory support devices are increasingly used in acute myocardial infarction complicated by cardiogenic shock (AMI-CS), despite limited evidence for their effectiveness. The aim of this study was to evaluate outcomes associated with use of the Impella device compared with intra-aortic balloon pump (IABP) and medical treatment in patients with AMI-CS., Methods: Data of patients with AMI-CS treated with the Impella device at European tertiary care hospitals were collected retrospectively. All patients underwent early revascularization and received optimal medical treatment. Using IABP-SHOCK II (Intraaortic Balloon Pump in Cardiogenic Shock II) trial inclusion and exclusion criteria, 372 patients were identified and included in this analysis. These patients were matched to 600 patients from the IABP-SHOCK II trial. The following baseline criteria were used as matching parameters: age, sex, mechanical ventilation, ejection fraction, prior cardiopulmonary resuscitation, and lactate. Primary end point was 30-day all-cause mortality., Results: In total, 237 patients treated with an Impella could be matched to 237 patients from the IABP-SHOCK II trial. Baseline parameters were similarly distributed after matching. There was no significant difference in 30-day all-cause mortality (48.5% versus 46.4%, P=0.64). Severe or life-threatening bleeding (8.5% versus 3.0%, P<0.01) and peripheral vascular complications (9.8% versus 3.8%, P=0.01) occurred significantly more often in the Impella group. Limiting the analysis to IABP-treated patients as a control group did not change the results., Conclusions: In this retrospective analysis of patients with AMI-CS, the use of an Impella device was not associated with lower 30-day mortality compared with matched patients from the IABP-SHOCK II trial treated with an IABP or medical therapy. To further evaluate this, a large randomized trial is warranted to determine the effect of the Impella device on outcome in patients with AMI-CS., Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT03313687.

Aims: Impaired left ventricular diastolic function leading to elevated left atrial pressures, particularly during exertion, is a key driver of symptoms and outcomes in heart failure with preserved ejection fraction (HFpEF). Insertion of an interatrial shunt device (IASD) to reduce left atrial pressure in HFpEF has been shown to be associated with short-term haemodynamic and symptomatic benefit. We aimed to investigate the potential effects of IASD placement on HFpEF survival and heart failure hospitalization (HFH)., Methods and Results: Heart failure with preserved ejection fraction patients participating in the Reduce Elevated Left Atrial Pressure in Patients with Heart Failure study (Corvia Medical) of an IASD were followed for a median duration of 739 days. The theoretical impact of IASD implantation on HFpEF mortality was investigated by comparing the observed survival of the study cohort with the survival predicted from baseline data using the Meta-analysis Global Group in Chronic Heart Failure heart failure risk survival score. Baseline and post-IASD implant parameters associated with HFH were also investigated. Based upon the individual baseline demographic and cardiovascular profile of the study cohort, the Meta-analysis Global Group in Chronic Heart Failure score-predicted mortality was 10.2/100 pt years. The observed mortality rate of the IASD-treated cohort was 3.4/100 pt years, representing a 33% lower rate (P = 0.02). By Kaplan-Meier analysis, the observed survival in IASD patients was greater than predicted (P = 0.014). Baseline parameters were not predictive of future HFH events; however, poorer exercise tolerance and a higher workload-corrected exercise pulmonary capillary wedge pressure at the 6 months post-IASD study were associated with HFH., Conclusions: The current study suggests IASD implantation may be associated with a reduction in mortality in HFpEF. Large-scale ongoing randomized studies are required to confirm the potential benefit of this therapy., (© 2018 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.)

Objective: We aimed to assess early neointimal healing by optical coherence tomography (OCT) 3 months after implantation of the ultrathin Orsiro® sirolimus-eluting stent with biodegradable polymer., Background: New generations of drug-eluting stents with biodegradable polymer have been developed to avoid the continued vascular irritation of durable polymers., Methods: In this prospective, open-label study, 34 patients received an Orsiro® sirolimus-eluting stent with biodegradable polymer. In a subgroup of patients (n = 15), the intervention was performed under OCT guidance. All patients underwent OCT-examination at three months. The primary endpoint was 3-month neointimal healing (NIH) score, calculated by weighing the presence of filling defects, malapposed and uncovered struts. Secondary endpoint was maturity of tissue coverage at 3 months., Results: At 3 months, NIH score was 13.7 (5.4-22), covered struts per lesion were 90% (84-97%), malapposed struts were 2.7% (0.8-5.4%) and rate of mature tissue coverage was 47% (42-53%). No target lesion failure occurred up to 12 months. Patients with OCT-guided stent implantation demonstrated a trend toward earlier stent healing as demonstrated by superior NIH scores (angio guided: 17.6% [8.8-26.4]; OCT-guided: 9.8% [4.0-15.5]; mean difference -8, [95%CI: -18.7-2.9], P = 0.123). This group had significantly more covered struts per lesion (angio-guided: 86% [82-90]; 95% [92-99]; mean difference 9% [95%CI: 3-15], P = 0.001)., Conclusion: The Orsiro® sirolimus-eluting stent with biodegradable polymer shows early vascular healing with a high rate of strut coverage at 3-month follow-up. OCT guided stent implantation had a positive impact on early vascular healing., (© 2018 Wiley Periodicals, Inc.)

Introduction: Pericardial effusion/tamponade (PE/PT) is a rare but serious complication following left atrial appendage closure (LAAC). It may be speculated that LAA contraction during sinus rhythm (SR) exerts mechanical force on the device that eventually leads to PE. We sought to determine the incidence and predictors of PE following LAAC using Watchman with special emphasis on the underlying heart rhythm during implant., Methods and Results: From 47 centers in 13 European countries 1,020 patients underwent LAAC and data on baseline rhythm were available from 1,010 patients (mean age 73 ± 9 years, 60% male, median CHA2DS2-VASc = 4). Data were collected via electronic case report forms. A Cox proportional hazard model was calculated adjusting for multiple variables: age, gender, number of recaptures, and device oversizing. During implant, 41% and 59% of patients were in SR and atrial fibrillation (AF), respectively. PE/PT rate was significantly lower in patients implanted during AF at day 30 postimplant (n = 1; 0.2% vs. n = 6; 1.5%; P = 0.02). No PE requiring intervention occurred in the AF group compared to 5 events (1.2%) in the SR group (P = 0.01). While univariate analysis identified SR and gender as predictors for PE/tamponade, multivariate analysis only showed a statistical trend for both variables., Conclusion: The overall incidence of PE/PT was very low after LAAC using Watchman. Although SR was not identified as an independent predictor of PE/PT, all events requiring intervention occurred in patients with SR. It may be advisable to perform an extended echocardiographic follow-up in that patient population., (© 2018 Wiley Periodicals, Inc.)

Aims: The study aimed to confirm the efficacy and safety of WATCHMAN LAA closure in atrial fibrillation patients unsuitable for oral anticoagulation., Methods and Results: The EWOLUTION registry prospectively collects all clinical data on 1,005 European patients implanted with a WATCHMAN device. Following the procedure, 605 patients (60.2%) received dual antiplatelet therapy according to the local standard; DAPT was discontinued in 85% of patients within one year. CHA2DS2-VASc and HAS-BLED scores were 4.61.6 and 2.41.2, respectively. The periprocedural SAE rate was 3.3% (2.0% major adverse cardiac events), mostly resolving without sequelae. Device embolisation or pericardial effusion occurred in one (0.2%) and two (0.3%) patients, respectively. TEE (median 62 days post implant, IQR: 47-97) confirmed effective sealing (no leak >5 mm) in 99.2% of patients. Device thrombus was present in 22 patients (4.0%), one patient developed a stroke. One-year mortality in the DAPT group was 9.6% (N=58) reflecting the advanced age and comorbidities in this population. The ischaemic stroke rate at one year was 1.4% (expected based on CHA2DS2-VASc: 7.5%), none fatal. The major bleeding rate was 2.5%, or 2.1% excluding periprocedural events (expected rate on VKA based on HAS-BLED: 5.1%)., Conclusions: LAA closure with the WATCHMAN device followed by DAPT therapy in a high-risk patient population is safe. At one year, the intervention is associated with a substantial risk reduction regarding ischaemic stroke and major bleeding compared to the expected rate based on CHA2DS2-VASc and HAS-BLED scores.

Background: Suboptimal implantation of everolimus-eluting bioresorbable vascular scaffolds (EE-BVS) leading to strut malapposition and lack of neointima coverage has been hypothesized to be linked to late BVS-thrombosis. Optical coherence tomography (OCT) allows assessing subtle differences in BVS-healing. We aimed to link 6-months OCT-data on EE-BVS coverage and malapposition to implantation technique and clinical outcome., Methods: Twenty-nine consecutive EE-BVS-patients were included. EE-BVS-implantation was guided by angiography in the first 17 patients (group 1). Vessel sizing prior to implantation and implantation result was assessed by OCT in the 12 following patients (group 2). EE-BVS-implantation was performed in both groups with adequate lesion preparation, sizing and systematic high-pressure post-dilatation. All patients received 6-months invasive control including OCT-analysis and clinical follow-up for 2 years., Results: The rate of uncovered struts was group 1: 10.8 ± 10.0%; group 2: 10.6 ± 8.2%, p = 0.934. Target lesion failure due to BVS-thrombosis occurred in 2/17 patients at 9 and 18 months (11.8%, group 1), and no patients in group 2 (p = 0.218)., Conclusions: Optical coherence tomography analysis at 6-months following EE-BVS-implantation finds almost 90% of struts to be covered. No difference between OCT vs. angiography-guided EE-BVS-implantation was observed. OCT at 6-months was not able to predict late BVS-thrombosis of EE-BVS.

In Europe left atrial appendage occluders (LAAO) are most frequently used in patients with contraindications for oral anticoagulation (OAC); therefore, the classical therapeutic OAC scheme from the PROTECT-AF trial (vitamin K antagonist plus acetylsalicylic acid) is usually changed to dual anti-platelet therapy (DAPT) after implantation of a Watchman® or Amulet® LAAO (St. Jude Medical/Abbott, Eschborn, Germany). For many years, patients with an LAAO received DAPT for 1-6 months. The current standard comprises DAPT for 3 months, followed by permanent acetylsalicylic acid monotherapy if the transesophageal echocardiogram excludes a thrombus at the site of the LAAO. In patients with high risk of bleeding, anti-platelet therapy can be stopped at 3 months after an individual risk-benefit calculation. There are no randomized studies on the risk of bleeding and stroke/embolism in patients with an LAA occluder under DAPT versus OAC. Experience from the EWOLUTION registry shows that NOACs may be used as an alternative with low bleeding and thrombus risks. In patients with a suboptimal implantation result, thrombus on the LAAO or specific risk factors, variations of the standard scheme have to be applied and if necessary lifelong DAPT or NOAC therapy has to be used. Thrombi on the LAAO occur in approximately 4-6% of patients and are associated with a very low short-term stroke risk.

Aims: While LAA closure has recently been incorporated into both European and US guidelines for stroke prevention, uncertainties regarding post-procedural drug therapy so far limit its adoption. The aim of this analysis is to compare real-world outcome data stratified for the post-procedural drug regimen employed., Methods and Results: One thousand and five patients were implanted with a WATCHMAN device in the prospective EWOLUTION study at 47 centres; 73.5% of the patients were deemed contraindicated for long-term OAC therapy. Here we report on three-month data including the first follow-up TOE exam for 94% of the study population. Following LAA closure, patients received DAPT, VKA, NOAC, single antiplatelet or no therapy (60.3%, 15.4%, 10.9%, 7% and 6.5%, respectively). Device thrombus (2.6%), stroke (0.4%) and major bleeding SAE (2.6%) rates were low overall and did not vary by post-implantation medication strategy. Patients on NOAC had the lowest bleeding rate, without an increase in device thrombus or stroke rates., Conclusions: LAA closure with the WATCHMAN device is feasible in patients with a relative or absolute contraindication to oral anticoagulation. Neither DAPT nor NOAC therapy leads to a significant increase in device thrombus, stroke or bleeding compared to the standard VKA regimen. Numerically, NOAC therapy had the lowest event rate.

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., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

NOAC therapy has become the standard for stroke prevention in patients with atrial fibrillation. Yet some patients suffer extracranial bleeding events or have other reasons to seek non-pharmacologic stroke protection. LAA occlusion with the WATCHMAN device has been proven safe and effective for such patients and is now recommended in current guidelines for this patient group; other devices also seek approval., (Copyright © 2017. Published by Elsevier Inc.)

Background: Oral anticoagulants (OACs) reduce stroke risks with nonvalvular atrial fibrillation (AF); however, they are underused because of absolute or relative contraindications due to real or perceived risk of bleeding. Although left atrial appendage closure is increasingly performed in OAC-ineligible patients, this has not been studied in a randomized controlled trial., Study Objectives: The ASAP-TOO study is designed to establish the safety and effectiveness of the Watchman left atrial appendage closure device in patients with nonvalvular AF who are deemed ineligible for OAC. The primary effectiveness end point is the time to first occurrence of ischemic stroke or systemic embolism. The primary safety end point includes all-cause death, ischemic stroke, systemic embolism, or device- or procedural-related event requiring open cardiac surgery or major endovascular intervention., Study Design: This is a multinational, multicenter prospective randomized trial. Patients meeting the inclusion criteria with CHA 2 DS 2 -VASc score≥2 and who are deemed by 2 study physicians to be unsuitable for OAC will be randomized in a 2:1 allocation ratio to Watchman versus control. Control patients will be prescribed single antiplatelet therapy or no therapy at the discretion of the study physician. Up to 888 randomized subjects will be enrolled from up to 100 global investigational sites. Both device group and control patients will have follow-up visits at 3, 6, and 12months and then every 6months through 60months., Summary: This trial will assess the safety and efficacy of Watchman in this challenging population of high-stroke risk AF patients., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Aims: Correct sizing of the ostium is a crucial step in left atrial appendage (LAA) occlusion procedures. However, unfavorable anatomy of the ostium often complicates the assessment of the true ostium diameter. We hypothesized that area-derived diameter (ADD) and perimeter-derived diameter (PDD) from three-dimensional transesophageal echocardiogram (3D-TEE) can facilitate this step of the procedure as compared with two-dimensional (2D) measurements., Methods and Results: For 55 patients within the ALSTER-LAA registry, retrospective analysis of PDD and ADD was correlated with 2D measurements used during the procedure to ascertain correct size of the Watchman device (Boston Scientific). The observed data were put into relation to the calculated area of the device with 10%-30% compression and the clinical outcome after 30 days. 3D area and perimeter measurements of the LAA ostium matched the calculated range of the different device sizes. Recapture during implantation, gaps <5 mm, and device size changes were more often observed when ADDs would also have suggested the use of a larger device., Conclusion: 3D ADDs and PDDs are feasible to use in device size decisions. Employing these measurements may allow operators to further reduce intraprocedural recapture maneuvers, peridevice leakage, and device size changes.

Background: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and the rate of ischemic stroke attributed to non-valvular AF is estimated at 5% per year. Several multi-center studies established left atrial appendage closure as a safe and effective alternative to oral anticoagulation, but there is a need for additional real world data., Methods: The purpose of this observational, prospective, single-arm, multicenter clinical study is to compile real-world clinical outcome data for WATCHMAN™ LAA (left atrial appendage) Closure Technology. One thousand subjects at up to 70 institutions in Europe, the Middle East, and Russia will be enrolled. Patients will be followed for 2 years after WATCHMAN implantation, according to standard medical practice. Primary endpoints include procedural and long-term data including stroke/embolism, bleeding, and death. This article presents the background of the LAAC device and describes the design of the study., Results: Results for peri-procedural analyses are expected toward the end of 2015; long-term follow-up data are expected in the latter half of 2017., Conclusion: The EWOLUTION study will formally expand knowledge of LAA closure into a broader real world setting. © 2015 Wiley Periodicals, Inc., (© 2015 Wiley Periodicals, Inc.)

Aims: Left atrial appendage closure is a non-pharmacological alternative for stroke prevention in high-risk patients with non-valvular atrial fibrillation. The objective of the multicentre EWOLUTION registry was to obtain clinical data on procedural success and complications, and long-term patient outcomes, including bleeding and incidence of stroke/transient ischaemic attack (TIA). Here, we report on the peri-procedural outcomes of up to 30 days., Methods and Results: Baseline/implant data are available for 1021 subjects. Subjects in the study were at high risk of stroke (average CHADS2 score: 2.8 ± 1.3, CHA2DS2-VASc: 4.5 ± 1.6) and moderate-to-high risk of bleeding (average HAS-BLED score: 2.3 ± 1.2). Almost half of the subjects (45.4%) had a history of TIA, ischaemic stroke, or haemorrhagic stroke; 62% of patients were deemed unsuitable for novel oral anticoagulant by their physician. The device was successfully deployed in 98.5% of patients with no flow or minimal residual flow achieved in 99.3% of implanted patients. Twenty-eight subjects experienced 31 serious adverse events (SAEs) within 1 day of the procedure. The overall 30-day mortality rate was 0.7%. The most common SAE occurring within 30 days of the procedure was major bleeding requiring transfusion. Incidence of SAEs within 30 days was significantly lower for subjects deemed to be ineligible for oral anticoagulation therapy (OAT) compared with those eligible for OAT (6.5 vs. 10.2%, P = 0.042)., Conclusion: Left atrial appendage closure with the WATCHMAN device has a high success rate in complete LAAC with low peri-procedural risk, even in a population with a higher risk of stroke and bleeding, and multiple co-morbidities. Improvement in implantation techniques has led to a reduction of peri-procedural complications previously limiting the net clinical benefit of the procedure., (© The Author 2016. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Left atrial appendage closure (LAAC), a device-based therapy for stroke prevention in patients with atrial fibrillation, is considered an alternative to oral anticoagulation therapy, particularly for patients at high risk of bleeding. Proof of concept has been demonstrated by the PROTECT AF and PREVAIL trials which evaluated the WATCHMAN device (Boston Scientific, Marlborough, MA, USA) versus warfarin, showing favourable outcome for the device group. The most commonly used devices for LAAC are the WATCHMAN and its successor, the WATCHMAN FLX (Boston Scientific) and the AMPLATZER Cardiac Plug and more recently the AMPLATZER Amulet device (both St. Jude Medical, St. Paul, MN, USA). The procedure is typically performed via a transseptal puncture under fluoroscopic and echocardiographic guidance. Technically, it is considered quite demanding due to the anatomic variability and fragility of the appendage. Careful material manipulation, adequate operator training, and good cardiac imaging and device sizing allow a safe, uneventful procedure. Post-procedure antithrombotic drug selection is based on the patient's history, indication and quality of LAAC.

Aims: Left main interventions require optimal initial results for good clinical outcome. Lesion preparation with the AngioSculpt Scoring Balloon (ASB) combined with the provisional T-stenting technique, if proven safe, might lead to better lumen gain and better clinical outcome. The aim of this registry was to investigate the safety and efficacy of the ASB as an option for lesion preparation in unprotected left main interventions (ULMI)., Methods and Results: Out of the all-comers unprotected left main registry (ULMI ALSTER), 47 patients with elective ULMI fulfilled the inclusion criteria for this study. The endpoints were acute lumen gain and 12-month MACCE. The drop-out rate was 4%. The provisional T-stenting technique was used in 97% of distal ULMI. The interventions were grouped according to use of ASB with an in-house, historical no-ASB patient control group. Lumen gain was 1.63±0.12 mm in the ASB group (n=34) and 1.35±0.12 mm in the no-ASB group (n=8, p=0.26), respectively. The use of the ASB was safe. Intravascular ultrasound (IVUS) data for 21 patients showed numerically greater lumen area gain of 3.14±0.33 mm2 in the ASB group compared to 2.33±0.88 mm2 with the conventional technique. TLR/TVR was 6.6% overall. Twelve-month MACCE was 12.5% (4/32) for ASB and 15.4% (2/13) in the historical control group., Conclusions: Adding ASB lesion preparation to the standard provisional T-stenting technique for ULMI is feasible and safe. Low TLR and TVR rates were observed. Lesion preparation led to a numerically larger lumen gain; the data allow valid power statistics to show this approach as leading to improved outcome in a possible randomised trial.

Background: Renal denervation is a new treatment considered for several possible indications. As new systems are introduced, the incidence of acute renal artery wall injury with relation to the denervation method is unknown. We investigated the acute repercussion of renal denervation on the renal arteries of patients treated with balloon-based and nonballoon-based denervation systems by quantitative angiography, intravascular ultrasound, and optical coherence tomography (OCT)., Methods and Results: Twenty-five patients (50 renal arteries) underwent bilateral renal denervation with 5 different systems, 3 of which balloon-based (Paradise [n=5], Oneshot [n=6], and Vessix V2 [n=5)]) and 2 nonballoon-based (Symplicity [n=6] and EnligHTN [n=3]). Analysis included quantitative angiography and morphometric intravascular ultrasound measurements pre and post procedure and assessment of vascular trauma (dissection, edema, or thrombus) by OCT after denervation. A significant reduction in lumen size by quantitative angiography and intravascular ultrasound was observed in nonballoon denervation but not in balloon denervation. By postdenervation OCT, dissection was seen in 14 arteries (32.6%). The percentage of frames with dissection was higher in balloon-based denervation catheters. Thrombus and edema were detected in 35 (81.4%) and 32 (74.4%) arteries, respectively. In arteries treated with balloon-based denervation that had dissection by OCT, the balloon/artery ratio was higher (1.24 [1.17-1.32] versus 1.10 [1.04-1.18]; P<0.01)., Conclusions: A varying extent of vascular injury was observed after renal denervation in all systems; however, different patterns were identified in balloon-based and in nonballoon-based denervation systems. In balloon denervation, the presence of dissections by OCT was associated with a higher balloon/artery ratio., (© 2015 American Heart Association, Inc.)

Rationale: The meta-Analysis of Cell-based CaRdiac study is the first prospectively declared collaborative multinational database, including individual data of patients with ischemic heart disease treated with cell therapy., Objective: We analyzed the safety and efficacy of intracoronary cell therapy after acute myocardial infarction (AMI), including individual patient data from 12 randomized trials (ASTAMI, Aalst, BOOST, BONAMI, CADUCEUS, FINCELL, REGENT, REPAIR-AMI, SCAMI, SWISS-AMI, TIME, LATE-TIME; n=1252)., Methods and Results: The primary end point was freedom from combined major adverse cardiac and cerebrovascular events (including all-cause death, AMI recurrance, stroke, and target vessel revascularization). The secondary end point was freedom from hard clinical end points (death, AMI recurrence, or stroke), assessed with random-effects meta-analyses and Cox regressions for interactions. Secondary efficacy end points included changes in end-diastolic volume, end-systolic volume, and ejection fraction, analyzed with random-effects meta-analyses and ANCOVA. We reported weighted mean differences between cell therapy and control groups. No effect of cell therapy on major adverse cardiac and cerebrovascular events (14.0% versus 16.3%; hazard ratio, 0.86; 95% confidence interval, 0.63-1.18) or death (1.4% versus 2.1%) or death/AMI recurrence/stroke (2.9% versus 4.7%) was identified in comparison with controls. No changes in ejection fraction (mean difference: 0.96%; 95% confidence interval, -0.2 to 2.1), end-diastolic volume, or systolic volume were observed compared with controls. These results were not influenced by anterior AMI location, reduced baseline ejection fraction, or the use of MRI for assessing left ventricular parameters., Conclusions: This meta-analysis of individual patient data from randomized trials in patients with recent AMI revealed that intracoronary cell therapy provided no benefit, in terms of clinical events or changes in left ventricular function., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01098591., (© 2015 American Heart Association, Inc.)

Aims: Renal denervation has emerged as a treatment option for patients with drug-resistant hypertension. This study was designed to assess the safety and effectiveness of the OneShotª Renal Denervation System., Methods and Results: RAPID is a prospective, multicentre, single-arm study which enrolled 50 patients at 11 clinical sites in Europe and New Zealand. Eligible patients had an office systolic blood pressure (SBP) ≥160 mmHg and were on a stable regimen of ≥3 antihypertensive medications including a diuretic. The primary safety endpoints were acute procedural safety at discharge and chronic procedural safety at six months. The primary effectiveness endpoint was the rate of office SBP reduction ≥10 mmHg at six months compared to baseline. While not a predefined endpoint, change in 24-hour ambulatory BP was evaluated. The mean baseline office SBP and diastolic BP measurements were 181.6±20.8 and 95.5±15.5 mmHg, respectively. Patients were on a mean of 5.1 antihypertensive medications at baseline. The mean office BP decreased by -20/-8 mmHg (p<0.0001/p=0.0002), and -22/-8 mmHg (p<0.0001/p=0.0014), from baseline to six and 12 months, respectively. The 24-hour ABPM was also significantly reduced by -11/-6 mmHg at six months compared to baseline (p=0.0085/p=0.037). There were no serious adverse events (SAE) at discharge related to groin and vascular access complication or renal artery injury or SAE/adverse device effects at six months., Conclusions: The results of the RAPID study demonstrate safe delivery of RF energy by the OneShot Renal Denervation System for renal sympathetic denervation and sustained efficacy, as evidenced by a significant reduction in office and 24-hour ABPM for six months, which was sustained up to 12 months. ClinicalTrials.gov Identifier: NCT01520506.