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Background: Interventional left atrial appendage occlusion (LAAO) mitigates the risk of thromboembolic events in nonvalvular atrial fibrillation (AF) patients with contraindication for long-term oral anticoagulation (OAC). Patients with prior stroke have a relevantly increased risk of recurrent stroke, so the effectiveness of LAAO could be reduced in this specific very high-risk patient group., Aim: This sub-study of the LAARGE registry investigates the effectiveness and safety of LAAO for secondary prevention in nonvalvular AF patients with a history of stroke., Methods: LAARGE is a prospective, non-randomised registry on the clinical reality of LAAO. The current sub-study employs data from index procedure and 1-year follow-up. Effectiveness and safety were assessed by documentation of all-cause mortality, non-fatal thromboembolism, procedure-related complications, and bleeding events., Results: A total of 638 patients were consecutively included from 38 hospitals in Germany and divided into two groups: 137 patients with a history of stroke (21.5%) and 501 patients without. Successful implantation was consistent between both groups (98.5% vs. 97.4%, p = NS), while peri-procedural MACCE and other complications were rare (0% vs. 0.6% and 4.4% vs. 4.0%, respectively; each p = NS). Kaplan-Meier estimate showed no significant difference in primary effectiveness outcome measure (freedom from all-cause death or non-fatal stroke) between both groups at follow-up (87.8% vs. 87.7%, p = NS). The incidence of transient ischemic attack or systemic embolism at follow-up was low (0% vs. 0.5% and 0.9% vs. 0%, respectively; each p = NS). Severe bleeding events after hospital discharge were rare (0% vs. 0.7%, p = NS)., Conclusions: Patients with prior stroke demonstrated similar effectiveness and safety profile for LAAO as compared to patients without prior stroke. LAAO could serve as a feasible alternative to OAC for secondary stroke prevention in this selected group of nonvalvular AF patients., Gov Identifier: NCT02230748., (© 2024. The Author(s).)

Background: Mental health problems are common in medical professionals and their development already starts at the undergraduate level. Studies on medical students can replicate higher prevalence for depression and burnout in this group, but they normally compare semester cohorts in an anonymized, cross-sectional approach and without a preventive perspective., Methods: We surveyed medical students at the beginning and end of their medical curriculum and collected data on burnout, depressivity, work related experience and salutogenesis parameters with validated self-administered questionnaires. Most remarkably we obtained the data from the same 58 individuals after 5.5 years, representing data of the highest quality in order to compare the mental health status at the beginning and the end of our students´ medical curriculum., Results: Our results not only show a severe exacerbation of physical, mental and emotional burnout in the participants at the end of their studies. The students also do not seem to have sufficient personal (resilience) or social resources (e.g. experience of social support) for coping with their mental health problems around the time of their graduation., Conclusions: Our participants reflect a development of mental health during their medical studies at university that is paving the way to the devastating prevalence of mental disorders and suicide in health professionals. From our results we derive an urgent need to integrate self-care and active coping in the learning goals of medical curricula., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier GmbH.)

Background: This study aims to report on the clinical and patient-reported outcomes in patients undergoing atrial fibrillation (AF) ablation with moderate or severe complications., Methods: The prospective, multicentre German Ablation Registry of patients undergoing catheter ablation was studied to compare outcomes of patients with moderate or severe complications (group I) and patients without or minor complications (group II)., Results: A total of 3865 patients (group I = 158, group II = 3707) were included in this analysis. Procedural success (92.4% vs 96.1%, p = 0.019) was lower and arrhythmia recurrence before discharge significantly higher in group I (15.8% vs 6.5%, p < 0.001). Hospital stays were longer in in group I (6 days vs 3 days, p < 0.001). The in-hospital rate of death, myocardial infarction (MI) or stroke was 6.4% in group I. Age was an independent predictor of in-hospital complications (HR1.43, 95% CI 1.18-1.72). In the 1-year follow-up, the composite outcome of death, MI, stroke, or major bleeding (8.5% vs 1.5%, p < 0.001) was significantly higher in group I. The majority of patients were still feeling safe during treatment regardless of occurred complications (88.4% vs 94.0%, p = 0.14) and would choose the same centre again in most cases (90.7% vs 92.9%, p = 0.59). Patients reported no or improved symptoms in both cohorts (77.3% vs 78.6%) without significant differences., Conclusion: Cardiovascular events in patients with severe complications are more common but patient satisfaction and symptomatic relief are high and comparable to those without complications., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Non-paroxysmal (NPAF) forms of atrial fibrillation (AF) have been reported to be associated with an increased risk for systemic embolism or death., Methods: Comparison of procedural details and long-term outcomes in patients (pts) with paroxysmal AF (PAF) against controls with NPAF in the prospective, multicentre observational registry of patients undergoing LAAC (LAARGE)., Results: A total of 638 pts (PAF 274 pts, NPAF 364 pts) were enrolled. In both groups, a history of PVI was rare (4.0% vs 1.6%, p = 0.066). The total CHA 2 DS 2 -VASc score was lower in the PAF group (4.4 ± 1.5 vs 4.6 ± 1.5, p = 0.033), while HAS-BLED score (3.8 ± 1.1 vs 3.9 ± 1.1, p = 0.40) was comparable. The rate of successful implantation was equally high (97.4% vs 97.8%, p = 0.77). In the three-month echo follow-up, LA thrombi (2.1% vs 7.3%, p = 0.12) and peridevice leak > 5 mm (0.0% vs 7.1%, p = 0.53) were numerically higher in the NPAF group. Overall, in-hospital complications occurred in 15.0% of the PAF cohort and 10.7% of the NPAF cohort (p = 0.12). In the one-year follow-up, unadjusted mortality (8.4% vs 14.0%, p = 0.039) and combined outcome of death, stroke and systemic embolism (8.8% vs 15.1%, p = 0.022) were significantly higher in the NPAF cohort. After adjusting for CHA 2 DS 2 -VASc and previous bleeding, NPAF was associated with increased death/stroke/systemic embolism (HR 1.67, 95% CI 1.02-2.72, p = 0.041)., Conclusion: Atrial fibrillation type did not impair periprocedural safety or in-hospital MACE patients undergoing LAAC. However, after one year, NPAF was associated with higher mortality., (© 2021. The Author(s).)

Introduction: Patients undergoing left atrial appendage closure (LAAC) are often severly anemic and close to the transfusion threshold. The aim was to investigate the prevalence of severe anemia in this cohort and if procedural safety is compromised compared with non-anemic patients., Methods and Results: Comparison of severly anemic patients (Hb < 80 g/l) vs. non-severly anemic patients in the prospective, multicentre observational LAARGE registry of patients undergoing LAAC. A total of 638 patients (anemia 22.3% vs non-anemic 77.7%) were included. Anemic patients were older (77.1 years ± 7.9 vs 75.6 years ± 7.9, p = 0.014), had more comorbidities, higher CHA2DS2-VASc (4.8 vs 4.4, p = 0.017) and higher HAS-BLED (4.3 vs 3.8, p < 0.001) scores. Implant success was not influenced by anemia (99.3% vs 97.2%). Severe in-hospital (0.7% vs 5.6%, p = 0.01) and overall complications (8.5% vs 13.7%, p = 0.11) were less common in patients with anemia, driven by fewer pericardial effusions. Mortality was higher in anemic patients and associated with an increased hazard ratio, albeit not significantly (16.0% vs 10.3%, HR 1.61 (95%-CI: 0.97-2.67), p = 0.06). In the one-year follow-up, composite outcome of death, stroke or systemic embolism occurred in 22/142 anemic and in 54/496 non-anemic patients with an adjusted HR of 1.04 (95%-CI 0.62-1.73, p = 0.89)., Conclusion: Severe anemia close to the transfusion threshold is common in patients undergoing LAAC. However, this does not influence in-hospital complications or implant success. One-year mortality is higher in anemic patients, mainly driven by co-morbidities., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Author(s).)

Data on the optimal treatment strategy for antiarrhythmic drug therapy (AAD) after catheter ablation for atrial fibrillation (AF) are inconsistent. The present study investigates whether postinterventional AAD leads to an improved long-term outcome. Patients from the prospective German Ablation Registry (n = 3275) discharged with or without AAD after catheter ablation for AF were compared regarding the rates of recurrences, reablations and cardiovascular events as well as patient reported outcomes during 12 months follow-up. In patients with paroxysmal AF (n = 2138) the recurrence rate did not differ when discharged with (n = 1051) or without (n = 1087) AAD (adjusted odds ratio (OR) 1.13, 95% confidence interval (CI) [0.95-1.35]). The reablation rate was higher and reduced treatment satisfaction was reported more often in those discharged with AAD (reablation: OR 1.30, 95% CI [1.05-1.61]; reduced treatment satisfaction: OR 1.76, 95% CI [1.20-2.58]). Similar rates of recurrences, reablations and treatment satisfaction were found in patients with persistent AF (n = 1137) discharged with (n = 641) or without (n = 496) AAD (recurrence: OR 1.22, 95% CI [0.95-1.56]; reablation: OR 1.21, 95% CI [0.91-1.61]; treatment satisfaction: OR 1.24, 95% CI [0.74-2.08]). The incidence of cardiovascular events and mortality did not differ at follow-up in patients discharged with or without AAD. In conclusion, the rates of recurrences, cardiovascular events and mortality did not differ between patients discharged with or without AAD after AF catheter ablation. However, AAD should be considered carefully in patients with paroxysmal AF, in whom it was associated with a higher reablation rate and reduced treatment satisfaction. Clinical trial registration: The trial has been registered under the number NCT01197638., (© 2021 The Authors. Pharmacology Research & Perspectives published by John Wiley & Sons Ltd, British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics.)

Introduction: Refractory angina (RA) is considered the end-stage of coronary artery disease, and often has no interventional treatment options. Coronary sinus Reducer (CSR) is a recent addition to the therapeutic arsenal, but its efficacy has only been evaluated on small populations. The RESOURCE registry provides further insights into this therapy., Methods: The RESOURCE is an observational, retrospective registry that includes 658 patients with RA from 20 centers in Europe, United Kingdom and Israel. Prespecified endpoints were the amelioration of anginal symptoms evaluated with the Canadian Cardiovascular Society (CCS) score, the rates of procedural success and complications, and MACEs as composite of all-cause mortality, acute coronary syndromes, and stroke., Results: At a median follow-up of 502 days (IQR 225-1091) after CSR implantation, 39.7% of patients improved by ≥2 CCS classes (primary endpoint), and 76% by ≥1 class. Procedural success was achieved in 96.7% of attempts, with 3% of procedures aborted mostly for unsuitable coronary sinus anatomy. Any complication occurred in 5.7% of procedures, but never required bailout surgery nor resulted in intra- or periprocedural death or myocardial infarction. One patient developed periprocedural stroke after inadvertent carotid artery puncture. At the last available follow-up, overall mortality and MACE were 10.4% and 14.6% respectively. At one, three and five years, mortality rate at Kaplan-Meier analysis was 4%, 13.7%, and 23.4% respectively., Conclusions: CSR implantation is safe and reduces angina in patients with refractory angina., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Pulmonary vein isolation is an established strategy for catheter ablation of atrial fibrillation (AF). However, in a significant number of patients, a repeat procedure is mandatory due to arrhythmia recurrence. In this study, we report safety data and procedural details of patients undergoing index ablation versus repeat ablation in a registry-based real-life setting., Methods: Patients from the German Ablation Registry, a prospective, multicentre registry of patients undergoing ablation between January 2007 and January 2010 were included., Results: A total of 4155 patients were enrolled in the study. Group I (index ablation) consisted of 3377/4155 (82.1%) and group II (repeat ablation) of 738/4155 (17.9%). Patients in group I had a significantly higher ratio of paroxysmal AF (69.3% vs 61.9%, p < 0.001) and significantly less persistent AF (30.7% vs 38.1%, p < 0.001). The repeat group showed significantly lower mean RF application duration (2580 s. vs 1960, p < 0.001), less fluoroscopy time (29 min. vs. 27 min., p < 0.001), less mean dose area product (DAP) (3744 cGy × cm 2 vs 3325 cGy × cm 2 , p = 0.001), and shorter study duration (181.2 min. vs 163.6 min., p < 0.001). No statistical difference between the groups was found in terms of mortality (0.3% vs 0.1%, p = 0.39), MACE (0.4% vs 0.3%, p = 0.58), MACCE (0.8% vs 0.6%, p = 0.47), composite safety endpoint (1.5% vs 1.4%, p = 0.76), and arrhythmia recurrence (43.8% vs 41.9%, p = 0.37) during 1-year follow-up. Both groups reported to have improved or no symptoms (80.4% vs 77.8%, p = 0.13)., Conclusion: Repeat catheter ablation is safe and provides a symptomatic relief comparable to index ablation. Repeat procedures are significantly shorter and use less fluoroscopy.

Background: The impact of structural heart disease (SHD) on safety and efficacy of catheter ablation of cavo-tricuspid isthmus-dependent atrial flutter (AFLU) is unclear. In addition, recent data suggest a higher complication rate of AFLU ablation compared to the more complex atrial fibrillation (AF) ablation procedure., Methods and Results: Within our prospective multicenter registry, 3526 consecutive patients underwent AFLU ablation at 49 German electrophysiological centers from 2007 to 2010. For the present analysis, the patients were divided into a group with SHD (n = 2164 [61.4%]; median age 69 years; 78.5% male) and a group without SHD (n = 1362 [38.6%]; 65 years; 70.3% male). In our study, SHD mainly encompasses coronary artery disease (52.6%), left ventricular ejection fraction ≤ 50% (47.6%), and hypertensive heart disease (28.0%). The primary ablation success (97%) and the incidence of major (0.2%) or moderate (1.2%) complications did not differ significantly between the two groups (P = 1.0 and 0.87, respectively). Vascular access site complications (0.6%), AV block III° (0.2%), and bleeding (≥ BARC II: 0.2%) were most common. After a median 562 days of follow-up, we observed a 2.92-fold higher one-year mortality (P < 0.0001) in patients with SHD. Patients' satisfaction with the ablation therapy (72.0% satisfied) was close to the overall subjective tachyarrhythmia-free rate (70.7%)., Conclusions: The present analysis demonstrates that ablation of cavo-tricuspid isthmus dependent AFLU in patients with SHD has a comparable, excellent risk-benefit profile in our large "real-world" registry. Mortality rates expectedly are higher in patients with SHD and AFLU compared to patients without SHD. CLINICALTRIALS.GOV: NCT01197638, http://clinicaltrials.gov/ct2/show/NCT01197638.

Introduction: Early discharge of patients with acute low-risk pulmonary embolism requires validation by prospective trials with clinical and quality-of-life outcomes., Methods: The multinational Home Treatment of Patients with Low-Risk Pulmonary Embolism with the Oral Factor Xa Inhibitor Rivaroxaban (HoT-PE) single-arm management trial investigated early discharge followed by ambulatory treatment with rivaroxaban. The study was stopped for efficacy after the positive results of the predefined interim analysis at 50% of the planned population. The present analysis includes the entire trial population (576 patients). In addition to 3-month recurrence (primary outcome) and 1-year overall mortality, we analysed self-reported disease-specific (Pulmonary Embolism Quality of Life (PEmb-QoL) questionnaire) and generic (five-level five-dimension EuroQoL (EQ-5D-5L) scale) quality of life as well as treatment satisfaction (Anti-Clot Treatment Scale (ACTS)) after pulmonary embolism., Results: The primary efficacy outcome occurred in three (0.5%, one-sided upper 95% CI 1.3%) patients. The 1-year mortality was 2.4%. The mean±sd PEmb-QoL decreased from 28.9±20.6% at 3 weeks to 19.9±15.4% at 3 months, a mean change (improvement) of -9.1% (p<0.0001). Improvement was consistent across all PEmb-QoL dimensions. The EQ-5D-5L was 0.89±0.12 at 3 weeks after enrolment and improved to 0.91±0.12 at 3 months (p<0.0001). Female sex and cardiopulmonary disease were associated with poorer disease-specific and generic quality of life; older age was associated with faster worsening of generic quality of life. The ACTS burden score improved from 40.5±6.6 points at 3 weeks to 42.5±5.9 points at 3 months (p<0.0001)., Conclusions: Our results further support early discharge and ambulatory oral anticoagulation for selected patients with low-risk pulmonary embolism. Targeted strategies may be necessary to further improve quality of life in specific patient subgroups., Competing Interests: Conflict of interest: S. Barco reports personal fees from Biocompatibles Group UK, LEO Pharma, Bayer, nonfinancial support from Bayer HealthCare and Daiichi Sankyo, grants from Sanofi, outside the submitted work. Conflict of interest: I. Schmidtmann reports grants from Merck Serono, outside the submitted work. Conflict of interest: W. Ageno reports grants from Bayer, personal fees from Boehringer Ingelheim, Daiichi Sankyo and Bristol Myers Squibb/Pfizer, outside the submitted work. Conflict of interest: T. Anušić has nothing to disclose. Conflict of interest: R.M. Bauersachs reports personal fees for lectures and advisory board work from Bayer HealthCare, Bristol Myers Squibb/Pfizer and Daiichi Sankyo, during the conduct of the study. Conflict of interest: C. Becattini reports personal fees for consultancy and lectures from Bayer HealthCare, Daiichi Sankyo and Bristol Myers Squibb, outside the submitted work. Conflict of interest: E. Bernardi has nothing to disclose. Conflict of interest: J. Beyer-Westendorf reports patient fees from the Center for Thrombosis and Hemostasis (CTH), University Medical Center Mainz, during the conduct of the study; grants and personal fees for advisory board work, lectures and travel support from Bayer, outside the submitted work. Conflict of interest: L. Bonacchini has nothing to disclose. Conflict of interest: J. Brachmann reports grants and personal fees from Medtronic, during the conduct of the study; grants from Medtronic, St Jude and Biotronik, outside the submitted work. Conflict of interest: M. Christ reports grants from the University of Mainz, during the conduct of the study. Conflict of interest: M. Czihal reports personal fees from Bayer HealthCare, Roche, AstraZeneca, MSD Sharp & Dohme and LEO Pharma, outside the submitted work. Conflict of interest: D. Duerschmied reports personal fees for lectures and nonfinancial support (travel costs) from Bayer, Pfizer, Daiichi Sankyo and CytoSorbents, outside the submitted work. Conflict of interest: K. Empen reports travel costs and personal fees for lectures from Bayer HealthCare, outside the submitted work. Conflict of interest: C. Espinola-Klein reports lecture fees from Bayer HealthCare, outside the submitted work. Conflict of interest: J.H. Ficker reports personal fees for lectures from Daiichi Sankyo, outside the submitted work. Conflict of interest: C. Fonseca reports personal fees for consultancy and lectures from Bayer, outside the submitted work Conflict of interest: S. Genth-Zotz has nothing to disclose. Conflict of interest: D. Jiménez has nothing to disclose. Conflict of interest: V-P. Harjola reports personal fees for lectures from Bayer, personal fees for lectures and advisory board work from Boehringer Ingelheim and Pfizer, personal fees for advisory board work from MSD, outside the submitted work. Conflict of interest: M. Held reports honoraria for advisory board work from Actelion, Bayer, Boehringer, MSD, Daiichi Sankyo and Roche, honoraria for lectures from Actelion, Bayer, Berlin-Chemie, Bristol Myers Squibb, MSD, Daichi Sankyo, Pfizer and OMT, grants from Actelion, outside the submitted work. Conflict of interest: L. Iogna Prat has nothing to disclose. Conflict of interest: T.J. Lange reports nonfinancial support for meeting attendance from the Center for Thrombosis and Hemostasis (CTH), University Medical Center Mainz, during the conduct of the study; personal fees from Bayer and Pfizer, outside the submitted work. Conflict of interest: M. Lankeit reports personal fees for lectures and nonfinancial support (travel costs) from Actelion, Bayer and Daiichi Sankyo, personal fees for lectures from MSD and Bristol Myers Squibb/Pfizer, grants from BRAHMS – Thermo Fisher Scientific, outside the submitted work. Conflict of interest: A. Manolis has nothing to disclose. Conflict of interest: A. Meyer has nothing to disclose. Conflict of interest: T. Münzel has nothing to disclose. Conflict of interest: P. Mustonen reports personal fees for lectures and advisory board work from Boehringer Ingelheim, Bayer, Sanofi-Anetis, LEO Pharma, Bristol Myers Squibb/Pfizer and MSD, outside the submitted work. Conflict of interest: U. Rauch-Kroehnert reports grants from Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Interdisziplinäres Zentrum Klinische Studien (IZKS) during the conduct of the study; personal fees from Bayer Vital, outside the submitted work. Conflict of interest: P. Ruiz-Artacho reports personal fees from Bayer, Daiichi Sankyo, Sanofi, Pfizer, LEO Pharma and Rovi, outside the submitted work. Conflict of interest: S. Schellong reports personal fees for lectures and consultancy from Bayer, Boehringer Ingelheim, Daiichi Sankyo and Aspen, grants and personal fees for lectures and consultancy from Bristol Myers Squibb, outside the submitted work. Conflict of interest: M. Schwaiblmair has nothing to disclose. Conflict of interest: R. Stahrenberg has nothing to disclose. Conflict of interest: L. Valerio has nothing to disclose. Conflict of interest: P.E. Westerweel has nothing to disclose. Conflict of interest: P.S. Wild reports grants and personal fees from Boehringer Ingelheim, Sanofi-Aventis, Bayer Vital and Bayer HealthCare, grants from Philips Medical Systems and Daiichi Sankyo Europe, personal fees from AstraZeneca, personal fees and equipment provision from DiaSorin, equipment provision from IEM, outside the submitted work. Conflict of interest: S.V. Konstantinides reports grants and provision of study drug from Bayer, during the conduct of the study; grants and personal fees for consultancy and lectures from Boehringer Ingelheim, Daiichi Sankyo, Biocompatibles Group UK and MSD, personal fees for consultancy and lectures from Bayer and Bristol Myers Squibb/Pfizer, grants and personal fees for lectures from Actelion, grants from Servier, outside the submitted work., (Copyright ©ERS 2021.)

Objectives: Chronic kidney disease (CKD) is associated with an increased complication rate after cardiac interventions. Although CKD has a high prevalence among atrial fibrillation patients, the impact of CKD on periprocedural complications and the outcome after an interventional left atrial appendage closure (LAAC) is unclear. The present study, therefore, aimed to investigate whether CKD influences the procedure's effectiveness and safety., Methods: LAARGE is a prospective, non-randomised registry. LAAC was conducted with different standard commercial devices, and the follow-up period was one year. CKD was defined by an eGFR < 60 mL/min/1.73 m 2 , and subgroups were further analysed (i.e. eGFR < 15, 15-29, and 30-59 mL/min/1.73 m 2 , respectively)., Results: Two hundred ninety-nine of 623 patients (48.0%) revealed a CKD. The prevalence of cardiovascular comorbidity, CHA 2 DS 2 -VASc score (4.9 vs. 4.2), and HAS-BLED score (4.3 vs. 3.5) was significantly higher in CKD patients (each p < 0.001). Implantation success was similarly high across all GFR groups (97.9%). Periprocedural MACCE (0.7 vs. 0.3%), and other major complications (4.7 vs. 3.7%) were comparably infrequent. Survival free of stroke was significantly lower among CKD patients within 1 year (82.0 vs. 93.0%; p < 0.001; consistent after adjustment for confounding factors), without significant accentuation in advanced CKD (i.e. eGFR < 30 mL/min/1.73 m 2 ; p > 0.05  vs. eGFR 30-59 mL/min/1.73 m 2 ). Non-fatal strokes were absolutely infrequent during follow-up (0 vs. 1.1%). Severe non-fatal bleedings were observed only among CKD patients (1.4 vs. 0%; p = 0.021)., Conclusions: Despite an increased cardiovascular risk profile of CKD patients, device implantation was safe, and LAAC was associated with effective stroke prevention across all CKD stages.

Left atrial appendage closure (LAAC) is an alternative to oral anticoagulation therapy in patients with non-valvular atrial fibrillation for the prevention of embolic stroke and systemic embolism. Although elderly patients (>75 years) have both higher ischemic and bleeding risk as compared with younger patients, they benefit from optimal anticoagulation. The subanalysis aimed to assess the indications, the safety, efficacy, and 1-year outcomes of interventional LAAC in elderly patients (≥ 75 years) compared with younger (< 75 years) patients in clinical practice. We analyzed data from the prospective Left-Atrium-Appendage Occluder Registry Germany. A total of 638 patients were included in the registry, 402 (63%) were aged ≥ 75 years. Compared with younger subjects, patients aged ≥75 were more likely to have higher CHA2DS2-VASC and HAS-BLED scores. Procedural success rate was high und similar in both groups (97.6%). Periprocedural adverse events were not statistically significant in groups (11.9% in <75 years vs 12.9% in ≥75 years; p = 0.80). At 1 year follow-up, all-cause mortality was higher in patients aged ≥75 compared withwith younger group (13.0% vs 7.8 %,p = 0.04), mainly due to non-cardiovascular causes (10.6% vs 6.0%). No significant differences in major bleeding, stroke, systemic embolism were observed. In conclusion, LAAC is feasible and safe in patients with AF at high stroke risk and with contraindications for OAC and should be considered as candidates for LAA closure. Elderly patients often present these characteristics and could benefit from this novel therapy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relations that could have appeared to influence the work reported in this study., (Copyright © 2020. Published by Elsevier Inc.)

Background: Interventional left atrial appendage closure (LAAC) effectively prevents thromboembolic events in atrial fibrillation patients. Impaired left ventricular ejection fraction (LVEF) increases not only the thromboembolic risk but also the complication rates of cardiac interventions. The LAAC procedure's benefit in patients with an impaired LVEF, therefore, has yet to be investigated., Methods: LAARGE is a prospective, non-randomized registry depicting the clinical reality of LAAC in Germany. Procedure was conducted with different standard commercial devices, and follow-up period was one year. In the sense of an as-treated analysis, patients with started procedure and documented LVEF were selected from the whole database., Results: 619 patients from 37 centers were categorized into one of three groups: LVEF > 55% (56%), 36-55% (36%), and ≤ 35% (8%). Prevalence of cardiovascular comorbidity increased with LVEF reduction (p < 0.001 for trend). CHA 2 DS 2 -VASc score was 4.3, 4.8, and 5.1 (p < 0.001), and HAS-BLED score was 3.7, 4.1, and 4.2 (p < 0.001). Implantation success was consistently high (97.9%), rates of intra-hospital MACCE (0.5%), and other major complications (4.2%) were low (each p = NS). Kaplan-Meier estimation showed a decrease in survival free of stroke with LVEF reduction during one-year follow-up (89.3 vs. 87.0 vs. 79.8%; p = 0.067), a trend which was no longer evident after adjustment for relevant confounding factors. Rates of non-fatal strokes (0.4 vs. 1.1 vs. 0%) and severe bleedings (0.7 vs. 0.0 vs. 3.1%) were consistently low across all groups (each p = NS)., Conclusions: LVEF reduction neither influenced the procedural success nor the effectiveness and safety of stroke prevention by LAAC., Trial Registration: ClinicalTrials.gov Identifier: NCT02230748.

Background/aim: Transportation of ovarian cortex prior to freezing is used clinically; however, basic investigations of ovarian storage are limited and the question remains what temperature is optimal for transport over long distances and time periods. The aim of this study was to evaluate the rate of follicular loss over various time periods under two different temperatures and assess whether ovarian follicle viability is affected following cryopreservation and thawing subsequent to the transportation of ovarian tissue., Materials and Methods: Pig ovaries were transported at 4°C (n=10) or at 38°C (n=10) prior to cryopreservation. At 0, 4, 12 and 24 h tissues were fixed for histological examination and a LIVE/DEAD Assay. At the same time-points ovarian tissues were cryopreserved and analysed after thawing., Results: Histological evaluation and LIVE/DEAD Assay of freshly transported ovarian tissue showed significantly better follicle survival at 4°C during transportation duration. In cryopreserved ovarian tissues the LIVE/DEAD Assay showed a significant difference in the number of intact and dead follicles at 24 h in favor of 4°C (p<0.05)., Conclusion: Ovarian tissue transportation should be kept at a minimum to prevent potential damage., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Aims: To investigate the efficacy and safety of early transition from hospital to ambulatory treatment in low-risk acute PE, using the oral factor Xa inhibitor rivaroxaban., Methods and Results: We conducted a prospective multicentre single-arm investigator initiated and academically sponsored management trial in patients with acute low-risk PE (EudraCT Identifier 2013-001657-28). Eligibility criteria included absence of (i) haemodynamic instability, (ii) right ventricular dysfunction or intracardiac thrombi, and (iii) serious comorbidities. Up to two nights of hospital stay were permitted. Rivaroxaban was given at the approved dose for PE for ≥3 months. The primary outcome was symptomatic recurrent venous thromboembolism (VTE) or PE-related death within 3 months of enrolment. An interim analysis was planned after the first 525 patients, with prespecified early termination of the study if the null hypothesis could be rejected at the level of α = 0.004 (<6 primary outcome events). From May 2014 through June 2018, consecutive patients were enrolled in seven countries. Of the 525 patients included in the interim analysis, three (0.6%; one-sided upper 99.6% confidence interval 2.1%) suffered symptomatic non-fatal VTE recurrence, a number sufficiently low to fulfil the condition for early termination of the trial. Major bleeding occurred in 6 (1.2%) of the 519 patients comprising the safety population. There were two cancer-related deaths (0.4%)., Conclusion: Early discharge and home treatment with rivaroxaban is effective and safe in carefully selected patients with acute low-risk PE. The results of the present trial support the selection of appropriate patients for ambulatory treatment of PE., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Introduction and Objectives: Despite the efficacy of oral anticoagulant (OAC) therapy, some patients continue to have a high residual risk and develop a stroke on OAC therapy (resistant stroke [RS]), and there is a lack of evidence on the management of these patients. The aim of this study was to analyze the safety and efficacy of left atrial appendage occlusion (LAAO) as secondary prevention in patients with nonvalvular atrial fibrillation who have experienced a stroke/transient ischemic attack despite OAC treatment., Methods: We analyzed data from the Amplatzer Cardiac Plug multicenter registry on 1047 consecutive patients with nonvalvular atrial fibrillation undergoing LAAO. Patientes with previous stroke on OAC therapy as indication for LAAO were identified and compared with patients with other indications., Results: A total of 115 patients (11%) with RS were identified. The CHA 2 DS 2 -VASc and the HAS-BLED score were significantly higher in the RS group (respectively 5.5±1.5 vs 4.3±1.6; P <.001; 3.9±1.3 vs 3.1±1.2; P <.001). No significant differences were observed in periprocedural major safety events (7.8 vs 4.5%; P=.1). With a mean clinical follow-up of 16.2±12.2 months, the observed annual stroke/transient ischemic attack rate for the RS group was 2.6% (65% risk reduction) and the observed annual major bleeding rate was 0% (100% risk reduction)., Conclusions: Patients with RS undergoing LAAO showed similar safety outcomes to patients without RS, with a significant reduction in stroke/transient ischemic attack and major bleeding events during follow-up. Adequately powered controlled trials are needed to further investigate the use of LAAO in RS patients., (Copyright © 2019 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Atrial arrhythmias are common in patients with implantable cardioverter-defibrillator (ICD). External shocks and internal cardioversion through commanded ICD shock for electrical cardioversion are used for rhythm-control. However, there is a paucity of data on efficacy of external versus internal cardioversion and on the risk of lead and device malfunction. We hypothesized that external cardioversion is noninferior to internal cardioversion for safety, and superior for successful restoration of sinus rhythm., Methods: Consecutive patients with ICD undergoing elective cardioversion for atrial arrhythmias at 13 centers were randomized in 1:1 fashion to either internal or external cardioversion. The primary safety end point was a composite of surrogate events of lead or device malfunction. Conversion of atrial arrhythmia to sinus rhythm was the primary efficacy end point. Myocardial damage was studied by measuring troponin release in both groups., Results: N=230 patients were randomized. Shock efficacy was 93% in the external cardioversion group and 65% in the internal cardioversion group ( P <0.001). Clinically relevant adverse events caused by external or internal cardioversion were not observed. Three cases of pre-existing silent lead malfunction were unmasked by internal shock, resulting in lead failure. Troponin release did not differ between groups., Conclusions: This is the first randomized trial on external vs internal cardioversion in patients with ICDs. External cardioversion was superior for the restoration of sinus rhythm. The unmasking of silent lead malfunction in the internal cardioversion group suggests that an internal shock attempt may be reasonable in selected ICD patients presenting for electrical cardioversion., Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03247738.

The vanadate-derivative dipotassium bisperoxo (5-hydroxy-pyridine-2-carboxylic) oxovanadate (V) (bpV(HOpic)), a pharmacological inhibitor of phosphatase and tensin homolog (PTEN), has been used in ovarian follicle culture systems for activation of follicular growth in vitro and suggested to be responsible for primordial follicle survival through indirect Akt activation. For pig ovarian tissue, it is still not clear which culture medium needs to be used, as well as which factors and hormones could influence follicular development; this also applies to bpV(HOpic) exposure. Therefore, ovarian cortical strips from pigs were cultured in 1 µM bpV(HOpic) (N = 24) or control medium (N = 24) for 48 hr. Media were then replaced with control medium and all tissue pieces incubated for additional 4 days. The strips were embedded in paraffin for histological determination of follicle proportions at the end of the culture period and compared to histological sections from tissue pieces without cultivation, which had been embedded right after preparation; comparison of healthy follicles for each developmental stage was performed to quantify follicle survival and activation. After 6-day culture, follicle activation occurred in tissue samples from both cultured groups but significantly more follicles showed progression of follicular development in the presence of 1 µM bpV(HOpic). The amount of non-vital follicles was not significantly increased during cultivation. BpV(HOpic) affects pig ovarian follicle development by promoting the initiation of follicle growth and development, similar as in rodent species and humans., (© 2019 Blackwell Verlag GmbH.)

Catheter ablation is nowadays the core treatment of atrial fibrillation (AF). Propofol infusion sedation is an accepted safety strategy; however, respiratory depression with respiratory variations is frequent. Noninvasive mechanical ventilation (NIV) added to deep sedation could improve procedural safety and success. We sought to assess the predictive factors and safety of NIV in combination to propofol deep sedation in left atrial ablation procedures. Procedural data from 252 consecutive patients who underwent left atrial ablation (166 [66%] persistent, 86 [34%] for paroxysmal AF) were analyzed. Sedation with 1% propofol was used in all procedures and controlled by electrophysiologists. Arterial blood gas analysis was performed regularly during the procedure. NIV was indicated for respiratory depression with pH <7.25 and pCO 2 >50 mm Hg or agitated patient with the need for more profound sedation. No patient needed endotracheal intubation, and no procedure was abandoned due to adverse effects of sedation. NIV was used in 25 patients (10%). Predictive factors for the use of NIV were high-dose propofol sedation (p = 0.010), persistent AF (p = 0.029), prolonged procedure time (p = 0.006), increased body mass index (p = 0.008) and presence of obstructive sleep apnea (OSA; p <0.001). In a Cox regression analysis, OSA was an independent factor for NIV use (p = 0.016). In conclusion, propofol deep sedation for patients who underwent left atrial ablation is safe. Adding NIV in high-risk patients (i.e., OSA, high body mass index, and lengthy procedure duration) provides better respiratory homeostasis and could impact long-term procedure results., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objectives: This study sought to investigate neurological disability after ischemic cerebrovascular events in patients treated with left atrial appendage (LAA) occlusion compared with those on warfarin., Background: Prior studies demonstrated that cerebrovascular events after LAA occlusion in patients with nonvalvular atrial fibrillation (NVAF) is largely nondisabling., Methods: From the 1,189 patients in the Korean LAA Occlusion and European Amplatzer Cardiac Plug Multi-Center Registry, 24 patients who experienced ischemic cerebrovascular events after LAA occlusion were enrolled. The neurological outcomes were compared with those in 68 patients who experienced an ischemic cerebrovascular event while on warfarin (Yonsei Stroke Registry). A modified Rankin scale (mRS) score of 3-6 categorized the cerebrovascular event as disabling. The mRS at discharge and at 3 and 12 months postcerebrovascular event in the two groups was compared., Results: The percentages of disabling cerebrovascular events were 37.5% and 58.8% at discharge (P = 0.07), 20.8% and 42.6% at 3 months (P = 0.08), and 12.5% and 39.7% at 12 months (P = 0.02) in the LAA occlusion and warfarin groups, respectively. The mRS was significantly lower in the LAA occlusion group at discharge and at 3 months (P < 0.01) and 12 months (P < 0.01) postcerebrovascular event despite no significant difference in mRS before cerebrovascular events (P = 0.98). Patients in the LAA occlusion group demonstrated a significant reduction in mRS between discharge and 12 months (P < 0.01), unlike patients in the warfarin group (P = 0.10)., Conclusions: Ischemic cerebrovascular events in patients who previously underwent percutaneous LAA occlusion for NVAF were more favorable than in patients on warfarin., (© 2018 Wiley Periodicals, Inc.)

Background: We aimed to compare patient characteristics and outcome of patients who had either undergone pulmonary vein isolation (PVI) or AV-node ablation (AVN) to control AF-related symptoms., Methods: From the German Ablation Registry, we analyzed data of 4444 patients (95%) who had undergone PVI and 234 patients (5%) with AVN., Results: AVN patients were on average 10 years older than PVI patients (71 ± 10 vs. 61 ± 10 years, p < 0.001) with 33% aged > 75 years. AVN patients had significantly more cardiovascular comorbidities (diabetes 21% vs. 8%, renal insufficiency 24% vs. 3%, underlying heart disease 80% vs. 36%, severely reduced left ventricular function 28% vs. 1%, all p < 0.001). Significantly more PVI patients had paroxysmal AF (63% vs. 18%, p < 0.001), and more AVN patients had long-standing persistent AF (44% vs. 7%, p < 0.001). At 1-year follow-up, mortality in the AVN group was much higher (Kaplan-Meier estimates 9.8% vs. 0.5%). 20% of PVI patients had undergone another ablation vs. 3% AVN patients (p < 0.001). Symptomatic improvement was equally achieved in about 80%. Re-hospitalization for cardiovascular reasons occurred significantly more often in PVI vs. AVN patients (31% vs. 18%, p < 0.001)., Conclusion: In the large German Ablation Registry, AVN ablation was performed much less frequently than PVI for symptomatic treatment of AF and typically in older patients with more comorbidity. Symptomatic improvement was similar in both groups. Hospitalizations for cardiovascular reasons were lower in AVN patients despite older age and more cardiovascular comorbidities. 20% of PVI patients had undergone at least one re-ablation.

Background: Exercise electrocardiography (ECG) is frequently used as a diagnostic measure in patients with suspected coronary artery disease (CAD). However, it has low sensitivity for the detection of CAD. Magnetocardiography (MCG) has been proposed as an alternative tool to accurately diagnose CAD., Objective: To date, a direct comparison of MCG to ECG has not been performed. This study sought to compare them for predicting the presence of significantly obstructive CAD., Methods: The patients with chest pain or other symptoms suggestive of CAD were enrolled in the analysis. All the patients underwent a clinical evaluation, exercise ECG, MCG test, and coronary angiography (CA). CAD was defined as stenosis ≥70% in at least one major coronary artery on quantitative analysis of CA., Results: We prospectively enrolled 202 consecutive patients who suggested CAD. The prevalence of CAD on CA was 39.1%. Sensitivity and accuracy for CAD diagnosis was higher for MCG compared with exercise ECG (sensitivities 68.4% and 40.5%, p <0.001, specificities 95.1% and 91.1%, p = 0.267, and accuracies 84.7% and 71.3%, p <0.001, respectively). There was no incremental diagnostic value of combined MCG and ECG to detect coronary artery disease (p = 0.357)., Conclusions: For the patients with intermediate to high risk of CAD, MCG exercise test provides better diagnostic accuracy for the detection of relevant obstruction of the epicardial coronaries when directly compared to exercise ECG.

Background: Magnetocardiography (MCG) is a non-invasive technique and to characterize the magnetic field, a pseudo-current conversion was used. The role of MCG in detecting left atrial (LA) dysfunction in patients with paroxysmal atrial fibrillation (PAF) is unknown., Objective: The aim of this study was to evaluate LA function using MCG in patients with PAF and healthy subjects, to identify possible indices to diagnose PAF., Methods: We enrolled a total of 70 subjects including 26 healthy volunteers (group 1) and 22 marathon runners (group 2) who did not exhibit any cardiac abnormalities, and 22 patients with PAF (group 3) which was documented by electrocardiography (ECG). Spatiotemporal activation graph (STAG) in base-apex and left-right direction was reconstructed. The maximum value of LA pseudo-current under rest and peak exercise were measured between the end of the P wave and beginning of the Q wave., Results: LA pseudo-current increase at peak exercise in PAF patients was significantly lower than in healthy volunteers and marathon runners (0.4±0.3 pT in group 3 vs. 0.8±0.3 pT in group 1 vs. 1.1±0.5 pT in group 2, p < 0.001). PAF patients had less pseudo-current increase in STAG at peak exercise than healthy volunteers and marathon runners (46% of 26 PAF patients, 81% of 22 healthy subjects vs. 81% of 22 marathon runners, p = 0.002). Sensitivity, specificity, and the area under the receiver-operator characteristics curve of LA pseudo-current increase at peak exercise for differentiating PAF patients from healthy subjects were 77%, 92%, and 0.896., Conclusions: MCG can provide important non-invasive information for detecting LA dysfunction in PAF patients. Therefore, MCG may help in differentiating PAF patients from healthy subjects.

Purpose: To retrospectively evaluate long-term treatment results following neoadjuvant chemoradiation (CRT) and radical surgery in patients with advanced adenocarcinoma (AC) of the oesophagus., Patients and Methods: Between 2005 and 2015, a total of 102 consecutive patients with a median age of 64 years (range, 44-86 years) and AC of the oesophagus were evaluated of whom 84 received a full CRT. A group of 51 patients was treated with neoadjuvant intent followed by radical surgery. A total dose of 50.4 Gy with mostly weekly paclitaxel/fluorouracil chemotherapy was administered. Six to eight weeks following CRT, a transthoracic subtotal oesophageal and proximal gastric resection was performed. Survival curves for overall survival and no evidence of disease (NED) survival (primary endpoints) were calculated according to Kaplan-Meier, and possible prognostic factors were evaluated by the log-rank test as well as by a Cox regression analysis., Results: Median follow-up time of the surviving patients was 48 months (range, 14-134 months). Overall and NED survival rates for patients of the study group (n = 51) were 40 and 32%, respectively, at 5 years. Age (p = 0.04), ypT category (p = 0.1) and the development of distant metastases (p = 0.05) were identified as (marginally) independent prognostic variables with impact on survival. Median survival time for patients of the study group (n = 51) was 45 ± 18 months (95%CI 9-81 months). Clear resection margins were achieved in 46/51 patients (92%). Regression rates with complete regression rare residual cancer and increased number of residual cells, but predominantly fibrosis were 33, 41, and 10%, respectively. Patterns of failure revealed local with distant recurrence in 2/51 (4%), regional recurrence alone in 2/51 (4%), and distant metastases in 27/51 (53%) patients., Conclusion: Neoadjuvant CRT in patients with AC of the oesophagus followed by thoracoabdominal surgery is a locally very effective concept. A significant tumour regression in almost 75% of the patients may stimulate prospective trials on the omission of radical surgery for some elderly patients. Due to a high rate of distant metastases further investigations in terms of effective systemic therapy may be warranted.

The number of patients with atrial fibrillation undergoing percutaneous coronary intervention (PCI) is increasing. Since these patients have a CHA 2 DS 2 -VASc score of 1 or higher, they should be treated with oral anticoagulation to prevent stroke. However, combination therapy with oral anticoagulation for prevention of embolic stroke and dual platelet inhibition for prevention of coronary thrombosis significantly increases bleeding complications. The optimal combination, intensity and duration of antithrombotic combination therapy is still not known. In the rather small randomized WOEST trial, the combination of a vitamin K antagonist (VKA) and clopidogrel decreased bleeding compared to the conventional triple therapy with VKA, clopidogrel and aspirin. In the PIONEER AF-PCI trial, two rivaroxaban-based treatment regimens significantly reduced bleeding complications compared to conventional triple therapy without increasing embolic or ischemic complications following PCI. Dual therapy with rivaroxaban and clopidogrel appeared to provide an optimal risk-benefit ratio. In the RE-DUAL PCI trial, dual therapy with dabigatran also reduced bleeding complications compared to conventional triple therapy. With respect to the composite efficacy end point of thromboembolic events (myocardial infarction, stroke, or systemic embolism), death, or unplanned revascularization dabigatran-based dual therapy was non-inferior to VKA-based triple therapy. The upcoming trials AUGUSTUS with apixaban and ENTRUST-PCI with edoxaban will further examine the use of NOACs in this setting. While recent guidelines recommend NOAC-based dual therapy in only a subset of patients (those who are at increased risk of bleeding), the available data now suggest that this should be the preferred choice for the majority of patients. Adding aspirin to this primary choice for up to 4 weeks in patients at especially high ischemic risk would likely prevent atherothrombotic events, but this needs further investigation. Taken together, it is time to adjust our practice and move to dual therapy consisting of a NOAC plus clopidogrel in most patients.

Background: Magnetocardiography (MCG) has been proposed as a non-invasive and functional technique with high accuracy for diagnosis of myocardial ischemia., Objective: This study sought to develop a novel scoring system of MCG for predicting the presence of significant obstructive coronary artery disease (CAD)., Methods: In a training set of 108 subjects, predictors of ≥70% stenosis in at least one major coronary vessel were prospectively identified from MCG variables. The final model was then retrospectively validated in a separate set of 45 subjects., Results: In the multivariable logistic regression, among those in the training set, elevated scores were predictive of ≥70% stenosis in all subjects (OR: 40.85; 95% CI: 6.28-265.90; p < 0.001). In the validation set, the score had an area under the receiver-operating characteristic curve of 0.91 (p < 0.001) for ≥70% stenosis. At an optimal cutoff, the score had 89% sensitivity, 77% specificity, 74% positive predictive value (PPV), 91% negative predictive value (NPV), and 82% accuracy for ≥70% stenosis. Partitioning the score into three levels of predicted risk, 91% of subjects could be identified or excluding CAD (81% PPV and 84% NPV)., Conclusion: We described an MCG score with high accuracy for predicting the presence of anatomically significant CAD.

History of major gastrointestinal (GI) bleeding may represent a frequent clinical indication for left atrial appendage occlusion (LAAO) in patients with non-valvular atrial fibrillation (AF). This study aims to investigate the procedural safety and long-term outcome of patients with previous major GI bleeding (MGIB) who underwent LAAO. Data from the Amplatzer Cardiac Plug multicenter registry on 1,047 patients were analyzed. Patients with previous MGIB as indication for LAAO were compared with patients without previous MGIB. A total of 151 patients (14.4%) with previous MGIB were identified. Periprocedural major bleeding events were more frequent in patients with previous MGIB (4.0% vs 0.8%, p = 0.001). With an average follow-up of 1.3 years, the observed annual rate of stroke/transient ischemic attack and major bleeding for patients with previous MGIB were 2.1% (61.4% relative reduction according to the Congestive Heart failure, Hypertension, Age ≥75 (doubled), Diabetes, Stroke (doubled), Vascular disease, Age 65-74, and Sex (female) [CHA 2 DS 2 -VASc] score) and 4.6% (20.1% relative reduction according to the expected rate based on the Hypertension, Abnormal renal/liver function (1 point each), Stroke, Bleeding history or predisposition, Labile INR, Elderly (>65 years), Drugs/alcohol concomitantly (1 point each) [HAS-BLED] score), respectively. In conclusion, in patients with non-valvular atrial fibrillation and previous MGIB, LAAO was associated with a low annual rate of stroke/transient ischemic attack. Periprocedural major bleeding events were more frequent in this specific population although the annual major bleeding rate showed a 20.1% relative risk reduction according to the HAS-BLED score., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Ventricular tachycardias (VT) in the healthy heart, also known as idiopathic VTs, often have a focal origin. Triggered activity due to delayed after-depolarization is the most likely mechanism of focal VTs. Localization of the site of origin of focal VTs is based on activation mapping with or without combination with pace mapping. The characteristic anatomic site of origin of idiopathic VTs is the right and left outflow tract. Other sites include the tricuspid and mitral annulus, the papillary muscles, and Purkinje fibers. Catheter ablation is indicated for monomorphic symptomatic VT and can be an alternative to antiarrhythmic drugs. Success rates are high, but mapping and ablation can be challenging. We review the main electrophysiological findings and the important clues for ablation of focal VTs. Specific considerations for each location are considered.

Background: In patients with non-valvular atrial fibrillation (NVAF), intracranial bleeding (ICB) constitutes a very challenging situation in which the rate of both ischemic and hemorrhagic events is increased. In these patients, left atrial appendage occlusion (LAAO) might represent a very valid alternative., Objectives: To investigate the procedural safety and long-term outcome of patients undergoing LAAO therapy due to previous ICB., Methods: Data from the Amplatzer Cardiac Plug multicenter registry on 1047 consecutive patients were analyzed. Patients with previous ICB as indication for LAAO were compared to patients with other indications., Results: A total of 198 patients (18.9%) with previous ICB were identified. The CHA 2 DS 2 -VASc score was similar (4.5±1.5 vs. 4.4±1.6, p=0.687) and the HAS-BLED score was higher in patients with previous ICB compared to those without (3.5±1.1 vs. 3.1±1.2, p<0.001). No significant differences in peri-procedural major adverse events were observed (2.5 vs 5.4%, p=0.1). Patients with previous ICB were more frequently on single acetylsalicylic acid therapy after LAAO (42.4% vs. 28.3%; p<0.001). With an average follow-up of 1.3years, the observed annual stroke/TIA rate (procedure and follow-up) for patients with previous ICB was 1.4% (75% relative risk reduction). The observed annual major bleeding rate (procedure and follow-up) for patients with previous ICB was 0.7% (89% relative risk reduction)., Conclusions: In patients with NVAF and previous ICB, LAAO seemed to be a safe procedure and was associated with a significant reduction in stroke/TIA and a remarkably low frequency of major bleeding during follow-up., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Aims: To analyse outcomes of supraventricular tachycardia (SVT) ablations performed within a prospective German Ablation Quality Registry., Methods and Results: Data from 12 566 patients who underwent catheter ablation of SVT between January 2007 and January 2010 to treat atrial fibrillation (AFIB, 37.2% of procedures), atrial flutter (AFL, 29.9%), atrioventricular nodal re-entrant tachycardia (AVNRT, 23.2%), atrioventricular re-entrant tachycardia (6.3%), and focal atrial tachycardia (AT, 3.4%) were prospectively collected. Patients were followed for at least 1 year. The periprocedural success rate was 96.3%, ranging from 84.3% (focal AT) to 98.9% (AVNRT). Kaplan-Meier mortality estimate at 1 year was 1.4% overall, and as high as 2.6% in the AFL group and 2.8% in the focal AT group. Recurrence of ablated or another symptomatic SVT was observed in 3783 (32.6%) of patients, ranging from 17.2% (AVNRT) to 45.6% (AFIB). Repeat ablation was performed in 12.0% of patients. After 1 year, 74.1% of survivors perceived ablation therapy as successful, 15.7% as partly successful, and 9.6% as unsuccessful. Even in those patients with arrhythmia recurrence, 76.0% perceived ablation as successful or partly successful and 89.6% would still undergo repeat ablation in the same institution., Conclusion: Ablation therapy for SVT is a safe procedure bringing symptomatic improvement and satisfaction to three quarters of patients after 1 year. Even in patients with arrhythmia recurrence, a high satisfaction level and adherence to the ablating institution could be documented. Strikingly high mortality and stroke rates in follow-up were observed in AFL patients, who apparently need consistent long-term anticoagulation and more medical attention., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.)

Aims: Although cardiac resynchronization therapy (CRT) is effective in patients with systolic heart failure (HF) and a wide QRS interval, a substantial proportion of patients remain non-responsive. The SonR contractility sensor embedded in the right atrial lead enables individualized automatic optimization of the atrioventricular (AV) and interventricular (VV) timings. The RESPOND-CRT study investigated the safety and efficacy of the contractility sensor system in HF patients undergoing CRT., Methods and Results: RESPOND-CRT was a prospective, randomized, double-blinded, multicentre, non-inferiority trial. Patients were randomized (2:1, respectively) to receive weekly, automatic CRT optimization with SonR vs. an Echo-guided optimization of AV and VV timings. The primary efficacy endpoint was the rate of clinical responders (patients alive, without adjudicated HF-related events, with improvement in New York Heart Association class or quality of life), at 12 months. The study randomized 998 patients. Responder rates were 75.0% in the SonR arm and 70.4% in the Echo arm (mean difference, 4.6%; 95% CI, -1.4% to 10.6%; P < 0.001 for non-inferiority margin -10.0%) (Table 2). At an overall mean follow-up of 548 ± 190 days SonR was associated with a 35% risk reduction in HF hospitalization (hazard ratio, 0.65; 95% CI, 0.46-0.92; log-rank P = 0.01)., Conclusion: Automatic AV and VV optimization using the contractility sensor was safe and as effective as Echo-guided AV and VV optimization in increasing response to CRT., Clinicaltrials.gov Number: NCT01534234., (© The Author 2016. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background/objectives: Magnetocardiography (MCG) has been proposed as a non-invasive and functional technique with high accuracy for diagnosis of myocardial ischemia. This study sought to investigate the incremental diagnostic value of combined quantitative and qualitative parameters of MCG to detect coronary artery disease (CAD)., Methods: Ninety six patients with suspected CAD who underwent coronary angiography were enrolled in the analysis to test the diagnostic accuracy of 2 MCG parameters (a quantitative parameter of the percent change of ST-segment fluctuation score and a qualitative parameter of non-dipole phenomenon)., Results: The best cut-off value for the percent change of ST-segment fluctuation score was -51.0%. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value were 78.1, 73.9, 82.0, 79.1, and 77.4, in the percent change of ST-segment fluctuation score and 86.5, 84.8, 88.0, 86.7, and 86.3 in non-dipole phenomenon. The area under the curve of receiver-operating characteristics was 0.79 for the percent change of ST-segment fluctuation score and 0.86 for non-dipole phenomenon (p<0.001). However, the incorporation of non-dipole phenomenon into a model with the percent change of ST-segment fluctuation score significantly improved C-statistics, indicating the enhancement of diagnostic performance in the detection of significant CAD (0.790 to 0.930; p<0.001)., Conclusions: Qualitative assessment of non-dipole phenomenon has a better diagnostic value than the quantitative parameter of percent change of ST-segment fluctuation score in the detection of significant CAD. Furthermore, this study found that the incorporation of non-dipole phenomenon into the percent change of ST-segment fluctuation score significantly improved the diagnostic performance of CAD detection., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: The presence of pulmonary hypertension (PH) severely aggravates the clinical course of heart failure with preserved ejection fraction (HFPEF) resulting in substantial morbidity and mortality. So far, neither established heart failure therapies nor pulmonary vasodilators have proven to be effective for this condition. Riociguat (Adempas®, BAY 63-2521), a stimulator of soluble guanylate cyclase, is a novel pulmonary and systemic vasodilator that has been approved for the treatment of precapillary forms of PH. With regard to postcapillary PH, the DILATE-1 study was a multicenter, double-blind, randomized, placebo-controlled single-dose study in subjects with PH associated with HFPEF. Although there was no significant change in the primary outcome measure, peak decrease in mean pulmonary artery pressure with riociguat versus placebo, riociguat significantly increased stroke volume without changing heart rate, pulmonary artery wedge pressure, transpulmonary pressure gradient or pulmonary vascular resistance. The present study is designed to test the efficacy of long-term treatment with riociguat in patients with PH associated with HFPEF., Methods/study Design: The DYNAMIC study is a randomized, double-blind, placebo-controlled, parallel-group, multicenter clinical phase IIb trial evaluating the efficacy, safety and kinetics of riociguat in PH-HFPEF patients. The drug will be given over 26 weeks to evaluate the effects of riociguat versus placebo. The primary efficacy variable will be the change from baseline in cardiac output at rest, measured by right heart catheter after 26 weeks of study drug treatment. Additional efficacy variables will be changes from baseline in further hemodynamic parameters, changes in left and right atrial area, right ventricular volume, as well as right ventricular ejection fraction measured by cardiac magnetic resonance imaging, and changes from baseline in World Health Organization (WHO) class and N‑terminal prohormone B‑type natriuretic peptide (NT-proBNP). The trial was registered on 25 August 2014 (EudraCT Number: 2014-003055-60; www.clinicaltrialsregister.eu )., Competing Interests: J. Mascherbauer has received fees and research grants from Bayer Healthcare, AOP Orphan, Actelion, Pfizer and Novartis. E. Grünig is member of the national and international advisory boards of Bayer HealthCare, Novartis, Actelion, Pfizer, GlaxoSmithKline and has received financial compensation for talks by Bayer HealthCare, Novartis, Actelion, Pfizer, United Therapeutics, Gilead and GlaxoSmithKline. M. Halank has received fees for board memberships (Actelion, Bayer and Novartis), lectures (Actelion, Bayer, GSK, Novartis, OMT and Pfizer), travel, accommodation and meeting expenses (Actelion, Bayer, GSK and Novartis) I.M. Lang is member of the speakers’ bureau of Actelion, Bayer, Astra Zeneca, Servier and is recipient of research grants from Actelion, Bayer, AOP Orphan and United Therapeutics. R. Frey is a former employee of Bayer Pharma involved in the development of riociguat and holds stocks in Bayer. D. Bonderman has received fees and research grants from Bayer Healthcare, AOP Orphan, United Therapeutics, Actelion, Pfizer and Novartis. W. Hohenforst-Schmidt, A.A. Kammerlander, I. Pretsch, R. Steringer-Mascherbauer S. Ulrich and M. Wargenau declare that they have no competing interests.

Background: LAA occlusion has a similar stroke prevention efficacy compared to anticoagulation treatment for non-valvular atrial fibrillation., Objective: The objective of this study was to assess the feasibility and safety of a modified Occlutech® left atrial appendage (LAA) closure device in a canine model., Methods: The device was implanted in 10 dogs (33±1kg) using fluoroscopy and transesophageal echocardiography (TEE) guidance. The modified Occlutech® LAA occlusion device was compared with the current version, the Watchman device, and the Amplazter cardiac plug (ACP). LAA occlusion and anchoring to the LAA were evaluated. All dogs were assessed using angiography, TEE, and a gross anatomy examination., Results: The 10 LAA occlusion devices were to be implanted into 10 dogs (5 modified Occlutech devices, 3 current version of Occlutech devices, 1 Watchman, and 1 ACP). LAA implantation was not performed in one dog due to transeptal puncture failure. The three current version of Occlutech devices were embolized immediately after implantation, so three modified devices of the same size were implanted securely without embolization. The mean implant size was 20.1±2.0mm. The devices chosen were a mean of 23.3±10.6% larger than the measured landing zone diameters. Post-implant angiography and TEE revealed well-positioned devices without pericardial effusion or impingement on surrounding structures., Conclusions: The results of this acute animal study suggested that a modified Occlutech® LAA occlusion device was feasible and had greater anchoring performance in canines. Additional large clinical studies are needed to evaluate safety and efficacy., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Aim: The aim of this study was to analyze the radiation usage in patients undergoing pulmonary vein isolation (PVI) in Germany and to evaluate the possibility to reduce radiation dose., Methods and Results: A total of 6617 patients with atrial fibrillation (AF) from the German ablation registry and the FREEZEplus registry (control group), who underwent first PVI between 2007 and 2014, were analyzed. In the second step, the effect of optimized conventional fluoroscopy and optimized 3D mapping use was evaluated in 526 consecutive patients with AF who underwent first PVI at the Klinikum Ludwigshafen (optimized group) between 2007 and 2014. In the control group, the median dose area product (DAP) for PVI was 34 Gy cm(2), and the median DAP rate was 1.3 Gy cm(2)/min. The DAP decreased from 37 to 28 Gy cm(2), whereas the DAP rate increased from 1.3 to 1.6 Gy cm(2)/min between 2007 and 2014. In the optimized group, optimized radiation application and use of 3D mapping resulted in a continuous decrease in the DAP from 67 to 2 Gy cm(2) and DAP rate from 1.0 to 0.2 Gy cm(2)/min., Conclusion: Currently, the median radiation exposure during PVI in Germany is 28 Gy cm(2). Optimized fluoroscopy by simple means can safely reduce the radiation dose to about 2 Gy cm(2) or even lower when using 3D mapping. Before introducing novel expensive technologies for radiation reduction optimizing of the conventional fluoroscopy is mandatory.

Tracheomalacia or tracheobronchomalacia (TM or TBM) is a common problem especially for elderly patients often unfit for surgical techniques. Several surgical or minimally invasive techniques have already been described. Stenting is one option but in general long-time stenting is accompanied by a high complication rate. Stent removal is more difficult in case of self-expandable nitinol stents or metallic stents in general in comparison to silicone stents. The main disadvantage of silicone stents in comparison to uncovered metallic stents is migration and plugging. We compared the operation time and in particular the duration of a sufficient Dumon stent fixation with different techniques in a patient with severe posttracheotomy TM and strongly reduced mobility of the vocal cords due to Parkinson's disease. The combined approach with simultaneous Dumon stenting and endoluminal transtracheal externalized suture under cone-beam computer tomography guidance with the Berci needle was by far the fastest approach compared to a (not performed) surgical intervention, or even purely endoluminal suturing through the rigid bronchoscope. The duration of the endoluminal transtracheal externalized suture was between 5 minutes and 9 minutes with the Berci needle; the pure endoluminal approach needed 51 minutes. The alternative of tracheobronchoplasty was refused by the patient. In general, 180 minutes for this surgical approach is calculated. The costs of the different approaches are supposed to vary widely due to the fact that in Germany 1 minute in an operation room costs on average approximately 50-60€ inclusive of taxes. In our own hospital (tertiary level), it is nearly 30€ per minute in an operation room for a surgical approach. Calculating an additional 15 minutes for patient preparation and transfer to wake-up room, therefore a total duration inside the investigation room of 30 minutes, the cost per flexible bronchoscopy is per minute on average less than 6€. Although the Dumon stenting requires a set-up with more expensive anesthesiology accompaniment, which takes longer than a flexible investigation estimated at 1 hour in an operation room, still without calculation of the costs of the materials and specialized staff that the surgical approach would consume at least 3,000€ more than a minimally invasive approach performed with the Berci needle. This difference is due to the longer time of the surgical intervention which is calculated at approximately 180 minutes in comparison to the achieved non-surgical approach of 60 minutes in the operation suite.

Lung cancer remains the leading cause of death in cancer patients. Severe treatment side effects and late stage of disease at diagnosis continue to be an issue. We investigated whether local treatment using 2-diethylaminoethyl-dextran methyl methacrylate copolymer with p53 (DDMC-p53) with or without cisplatin and/or microwave ablation enhances disease control in BALBC mice. We used a Lewis lung carcinoma cell line to inoculate 140 BALBC mice, which were divided into the following seven groups; control, cisplatin, microwave ablation, DDMC-p53, DDMC-p53 plus cisplatin, DDMC-p53 plus microwave, and DDMC-p53 plus cisplatin plus microwave. Microwave ablation energy was administered at 20 W for 10 minutes. Cisplatin was administered as 1 mL/mg and the DDMC-p53 complex delivered was 0.5 mL. Increased toxicity was observed in the group receiving DDMC-p53 plus cisplatin plus microwave followed by the group receiving DDMC-p53 plus cisplatin. Infection after repeated treatment administration was a major issue. We conclude that a combination of gene therapy using DDMC-p53 with or without cisplatin and microwave is an alternative method for local disease control. However, more experiments are required in a larger model to identify the appropriate dosage profile.

Novel therapies for lung cancer are being explored nowadays with local therapies being the tip of the arrow. Intratumoral chemotherapy administration and local microwave ablation have been investigated in several studies. It has been previously proposed that lipiodol has the ability to modify the microenvironment matrix. In our current study we investigated this theory in BALBC mice. In total 160 BALBC mice were divided in eight groups: a) control, b) cisplatin, c) microwave, d) microwave and lipiodol, e) cisplatin and lipiodol, f) microwave and cisplatin, g) lipiodol and h) lipiodol, cisplatin and microwave. Lewis lung carcinoma cell lines (10(6)) were injected into the right back leg of each mouse. After the 8th day, when the tumor volume was about 100mm(3) the therapy application was initiated, once per week for four weeks. Magnetic resonance imaging was performed for each tumor when a mouse died or when sacrificed if they were still alive by the end of the experiment (8-Canal multifunctional spool; NORAS MRI products, Gmbh, Germany). Imaging and survival revealed efficient tumor apoptosis for the groups b,c,d,e and f. However; severe toxicity was observed in group h and no follow up was available for this group after the second week of therapy administration. Lipiodol in its current form does assist in a more efficient way the distribution of cisplatin, as the microwave apoptotic effect. Future modification of lipiodol might provide a more efficient method of therapy enhancement. Combination of drug and microwave ablation is possible and has an efficient apoptotic effect.

Background: Although magnetocardiography (MCG) has been proposed as a non-invasive technique with high accuracy for functional diagnosis of myocardial injury, the validation of MCG against fractional flow reserve FFR in diagnosing coronary artery disease (CAD) has not yet been established. The goal of the study was to determine the diagnostic accuracy of MCG versus invasively determined FFR in patients with suspected or known CAD., Methods: Forty seven patients with suspected CAD (35 men; mean age 69 years) who underwent coronary angiography and FFR measurement were enrolled. FFR ≤ 0.8 was considered to indicate significant myocardial ischemia. The change of ST-segment fluctuation score from rest to stress was calculated from the MCG. In addition, two blinded cardiologists assessed MCG images that were visualized by post-processing method, bull's-eye mapping., Results: The best cut-off value of the percent change of ST-segment fluctuation score was -39.0% with sensitivity of 86.7% and specificity of 73.9%. Sensitivity, specificity, diagnostic accuracy, and the area under the receiver-operator characteristics curve of bull's-eye mapping for the detection of significant CAD were 90.5%, 92.3%, 91.5%, and 0.914 on a patient basis and 90.0%, 93.8%, 92.3%, and 0.919 by coronary territory, respectively., Conclusions: MCG accurately detects functionally significant CAD as defined by using FFR, provides an assessment of ischemic status in agreement with the change of ST-segment fluctuation score, and accurately localizes the ischemic territory in bull's eye mapping. Therefore, MCG may provide an incremental value for prediction of myocardial ischemia non-invasively and safely in clinical practice with fast examination time.

The aim of the study is to evaluate the feasibility and safety of a new left atrial appendage (LAA) occluder. Twelve pigs were included. In 2 pigs the implantation process failed due to pericardial tamponade in 1 pig and device embolization in the other pig. The placement of the devices was controlled via TEE and fluoroscopy. After 6 weeks of implantation the hearts were explanted. The devices were found to be easy to deploy and showed a very good adaptation to the LAA tissue. Eight out of 10 pigs had full closure of the LAA directly after implantation. After six weeks, due to the self-modelizing properties of the device, all pigs had a full closure of the LAA. The macroscopic evaluation of the explanted hearts showed that all devices were securely integrated in LAA tissues. There was one case of mild pericarditis but no macroscopic signs of inflammation on the device surrounding endocardium. The explantation revealed that device loops had penetrated the LAA tissue in three pigs. However, no signs of bleeding, pericardial effusion, or other damage to the LAA wall could be detected and the pigs were in good condition with normal weight gain and no clinical symptoms. The Occlutech® LAA occluder achieved complete closure of the LAA in all pigs, and remained in the LAA, with benign healing and no evidence of new thrombus or damage to surrounding structures. Moreover, the uncompromised survival of all implanted pigs demonstrates the feasibility and safety of the device., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background: The assessment of an increasing number of molecular markers is becoming a standard requirement from endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) specimens. However, it is unclear how many needle passes should be performed and the amount of lung cancer cells that should be sent for molecular analyses. The objective of this study was to determine if it is feasible to divide the material obtained by EBUS-TBNA to allow for molecular analysis without compromising the accuracy of mediastinal staging., Objective: We aimed to determine if dividing EBUS-TBNA specimens has a negative impact on either histopathological diagnosis or molecular analysis., Methods: EBUS-TBNA was performed in 249 enlarged lymph nodes. Negative or ambiguous histopathological results were confirmed by surgical means and clinical follow-up over 6 months. The tissue obtained by EBUS-TBNA was placed onto a glass slide and divided for histopathological workup and molecular analysis. The number of passes was recorded. Both the accuracy of the mediastinal lymph node staging and the applicability of the sample division for molecular analysis were assessed., Results: Each lymph node was punctured an average of 3.18 times and division of the obtained material for diagnosis and molecular analysis was feasible in all cases. The sensitivity and accuracy of the mediastinal lymph node staging were 96.6% and 97.6%, respectively. A cytokeratin (CK)-19-mRNA concentration-based molecular test was feasible in 74.1% of cases., Conclusion: Dividing EBUS-TBNA samples for both histopathological diagnosis and molecular testing is feasible and does not compromise the accuracy of mediastinal staging. This method may be an alternative to taking additional needle passes for molecular analyses.

Interleukin 7 and 15 are considered powerful pro-inflammatory cytokines, they have the ability to destabilize chromosomes and induce tumorigenesis. Additionally, they can control malignancy proliferation by influencing the tumor microenvironment and immune system. Immunotherapy has been proposed as a treatment modality for malignancy for over a decade; the exact mechanisms of action and pathways are still under investigation. Interleukin 7 and 15 have been extensively investigated in hematological malignancies since their mode of action influences the stimulation of the immune system in a more direct way than other malignancies such as lung, melanoma, and breast, renal and colorectal cancer.