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Abstract Background In patients with iron deficiency anemia, ferric carboxymaltose (FCM) and ferric derisomaltose (FDI) allow high-dose iron repletion. While FCM is reported to induce hypophosphatemia, the frequency of hypophosphatemia after an equivalent dosage of FDI had not been assessed prospectively. Methods In the prospective, single-center, double-blind HOMe aFers study, 26 women with iron deficiency anemia (hemoglobin

Zusammenfassung  Die kardiale Resynchronisationstherapie (CRT) hat sich bei Patienten mit fortgeschrittener systolischer Herzinsuffizienz und verlängerter QRS-Dauer etabliert, wenngleich 30–45% der Patienten nicht auf die Therapie ansprechen. Unter der Annahme, dass der Hauptmechanismus der CRT in der Korrektur eines dyssynchronen kardialen Kontraktionsablaufs besteht, wird zur besseren Vorhersage des CRT-Erfolges eine Fülle von echokardiographischen Dyssynchroniemarkern vorgeschlagen. Die Brauchbarkeit dieser Indizes ist durch eine multizentrische Studie kürzlich in Frage gestellt worden. In dieser Übersicht werden die unterschiedlichen Ursachen einer erfolglosen CRT aufgeschlüsselt, die verschiedenen Ebenen und Mechanismen kardialer Asynchronie beschrieben und die verfügbaren echokardiographischen Verfahren zur Dyssynchroniebeurteilung kritisch dargestellt. Auf der Grundlage der Daten der großen randomisierten Multicenterstudien und vor dem Hintergrund der CRT-Leitlinien der nationalen und internationalen Fachgesellschaften wird eine Rationale zur Evaluation von Patienten für die CRT vorgeschlagen. [ABSTRACT FROM AUTHOR]

Background: The clinical relevance of cardiac troponin (cTn) elevation in takotsubo syndrome (TTS) remains uncertain. The present study sought to investigate the role of cardiac troponin (cTn) elevations in mortality prediction of patients with Takotsubo syndrome (TTS)., Methods: Patients enrolled in the International Takotsubo (InterTAK) Registry from January 2011 to February 2020 with available data on peak cTn levels were included in the analysis. Peak cTn levels during the index hospitalization were used to define clinically relevant myocardial injury. The threshold at which clinically relevant myocardial injury drives mortality at 1 year was identified using restricted cubic spline analysis., Results: Out of 2'938 patients, 222 (7.6%) patients died during 1-year follow-up. A more than 28.8-fold increase of cTn above the upper reference limit was identified as threshold for clinically relevant myocardial injury. The presence of clinically relevant myocardial injury was significantly associated with an increased risk of mortality at 5 years (adjusted HR 1.58, 95% CI 1.18-2.12, p =.002). Clinically relevant myocardial injury was related to an increased 5-year mortality risk in patients with apical TTS (adjusted HR 1.57, 95% CI 1.21-2.03, p =.001), in presence of physical stressors (adjusted HR 1.60, 95% CI 1.22-2.11, p =.001), and in absence of emotional stressors (adjusted HR 1.49, 95% CI, 1.17-1.89, p =.001)., Conclusion: This study for the first time determined a troponin threshold for the identification of TTS patients at excess risk of mortality. These findings advance risk stratification in TTS and assist in identifying patients in need for close monitoring and follow-up., (© 2024 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.)

Background: Randomized sham-controlled trials have confirmed the efficacy and safety of catheter-based renal denervation in hypertension. Data on the very long-term effects of renal denervation are scarce., Aims: This study evaluates the 10-year safety and efficacy of renal denervation in resistant hypertension., Methods: This prospective single-center study included patients with resistant hypertension undergoing radio-frequency renal denervation between 2010 and 2012. Office blood pressure, 24-h ambulatory blood pressure, antihypertensive medication, color duplex sonography, and renal function were assessed after 1-, 2- and 10-years., Results: Thirty-nine patients completed the 10-year follow-up (mean follow-up duration 9.4 ± 0.7 years). Baseline office and 24-h ambulatory systolic blood pressure were 164 ± 23 mmHg and 153 ± 16 mmHg, respectively. After 10 years, 24-h ambulatory and office systolic blood pressure were reduced by 16 ± 17 mmHg (P < 0.001) and 14 ± 23 mmHg (P = 0.001), respectively. The number of antihypertensive drugs remained unchanged from 4.9 ± 1.4 to 4.5 ± 1.2 drugs (P = 0.087). The estimated glomerular filtration rate declined within the expected range from 69 (95% CI 63 to 74) to 60 mL/min/1.73m 2 (95% CI 53 to 68; P < 0.001) through 10-year follow-up. Three renal artery interventions were documented for progression of pre-existing renal artery stenosis in two patients and one patient with new-onset renal artery stenosis. No other adverse events were observed during the follow-up., Conclusion: Renal denervation was safe and sustainedly reduced ambulatory and office blood pressure out to 10 years in patients with resistant hypertension., (© 2024. The Author(s).)

Background: The perception of takotsubo syndrome (TTS) has evolved significantly over the years, primarily driven by increased recognition of acute complications and mortality., Objectives: This study aimed to explore temporal trends in demographic patterns, risk factors, clinical presentations, and outcomes in patients with TTS., Methods: Patients diagnosed with TTS between 2004 and 2021 were enrolled from the InterTAK (International Takotsubo) registry. To assess temporal trends, patients were divided into 6 groups, each corresponding to a 3-year interval within the study period., Results: Overall, 3,957 patients were included in the study. There was a significant demographic transition, with the proportion of male patients rising from 10% to 15% (P = 0.003). Although apical TTS remained the most common form, the diagnosis of midventricular TTS increased from 18% to 28% (P = 0.018). The prevalence of physical triggers increased from 39% to 58% over the years (P < 0.001). There was a significant increase in 60-day mortality over the years (P < 0.001). However, a landmark analysis excluding patients who died within the first 60 days showed no differences in 1-year mortality (P = 0.150)., Conclusions: This study of temporal trends in TTS highlights a transition in patients demographic with a growing prevalence among men, increasing recognition of midventricular TTS type, and increased short-term mortality and rates of cardiogenic shock in recent years. This transition aligns with the rising prevalence of physical triggers, as expression of increased recognition of TTS in association with acute comorbidities., Competing Interests: Funding Support and Author Disclosures Dr Templin has received institutional grants from Abbott Vascular, Medtronic, and SMT; and has received consulting grants from Biotronik, Microport, and Innova. Dr Airaksinen has received grants or has contracts with the Finnish Foundation for Cardiovascular Research; and has received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Bayer, Pfizer, Boehringer Ingelheim, and AstraZeneca. Dr Bauersachs has received grants from or has contracts with Abiomed, CVRx, Norgine, Roche, and Zoll; holds patents PCT/EP2007/008772 and PCT/EP2009/051986 for microRNA and downstream targets for diagnostics and therapeutic purposes; has received consulting fees from Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Cardior, Corvia, CVRx, Edwards, Norgine, Novartis, Pfizer, Roche, and Vifor; and has received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Cardior, CVRx, Norgine, Novartis, Pfizer, and Vifor. Dr Boehm has received grants from or has contracts with Deutsche Forschungsgemeinschaft research support (DFG, SFB-TTR 219, S-01); has received speaker honoraria from Abbott, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cytokinetics, Medtronic, Novartis, Servier, and Vifor; and is on the advisory board of Amgen, Bayer, Boehringer Ingelheim, Cytokinetics, Medtronic, Novartis, Pfizer, ReCor, Servier, and Vifor. Dr Ferreira has received payments for lectures, presentations, speakers bureaus, manuscript writing, or educational events from A Menarini, Medinfar, Bayer, AstraZeneca, Biotronik, and Medtronic; and has received payments for participation on a Data Safety Monitoring Board or Advisory Board from Medtronic. Dr Dichtl has received consulting fees from Reata. Dr Kaiser has received consulting fees from the Swiss Federal Office of Public Health; and has received support for attending meetings and/or travel from Medtronic, Abbott, and Europa Organization. Dr Kobza has received institutional grants on behalf of the Luzerner Kantonsspital from Biosense Webster, Boston Scientific, Biotronik, Medtronik, and Sis-Medical; and has received consulting fees from Biosense Webster, Biotronik, and Medtronic. Dr Koenig has received grants and provision of reagents to the institution from Singulex, Dr.Beckmann Pharma, Abbott, and Roche Diagnostics; has received consulting fees from AstraZeneca, Novartis, Amgen, Pfizer, The Medicines Company, DalCor Pharmaceuticals, Kowa, Corvidia Therapeutics, OMEICOS, Daiichi-Sankyo, Novo Nordisk, New Amsterdam Pharma, TenSixteen Bio, Esperion, and Genentech; and has received lecture fees from Bristol Myers Squibb, Novartis, Amgen, Berlin-Chemie, Sanofi, and AstraZeneca. Dr Lüscher has received research or educational grants to the institution from Abbott, Amgen, AstraZeneca, Boehringer Ingelheim, Daiichi-Sankyo, Novartis, Novo Nordisk, Sanofi, and Vifor; is the president elect of the European Society of Cardiology; is chairman of the research committee of the Swiss Heart Foundation; is President of the Board of the Zurich Heart House; and is Trustee of the London Heart House. Dr Karakas has received grants or has contracts with Vifor Pharma and Daiichi-Sankyo; has received consulting fees or payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Vifor, Pharmacosmos, and Sphingotec; and has received equipment, materials, drugs, medical writing, gifts or other services from Sphingotec and Vifor Pharma. Dr Niederseer has received consulting fees from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Daiichi-Sankyo, Gerson Lehmann Group (GLG) Consulting, Novo Nordisk, Pfizer and Zoll; has received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Daiichi-Sankyo, Novartis, Novo Nordisk, and Pfizer; and has received support for attending meetings and/or travel from Abbott, Amgen, Bayer, and Novo Nordisk. Dr Roffi has received institutional research grants from Boston Scientific, Cordis, Terumo, Biotronik, and Medtronic. Dr Ruschitzka has not received personal payments by pharmaceutical companies or device manufacturers in the last 3 years; the Department of Cardiology (University Hospital of Zurich/University of Zurich), however, reports research, educational, and/or travel grants from Abbott, Abiomed, Alexion, Amgen, AstraZeneca, At the Limits Ltd, Bayer, Berlin Heart, B. Braun, Biosense Webster, Biosensors Europe AG, Biotronik, Bristol Myers Squibb, Boehringer Ingelheim, Boston Scientific, Bracco, Cardinal Health Switzerland, Concept Medical, Corteria, CSL, Daiichi-Sankyo, Diatools AG, Edwards Lifesciences, Guidant Europe NV, Hamilton Health Sciences, IHF, Innosuisse, Johnson/Johnson, Kaneka Corporation, Kantar, Kiniksa, Labormedizinisches Zentrum, MedAlliance, Medical Education Global Solutions, Medtronic, MicroPort, MSD, Mundipharma Medical Company, Novartis, Novo Nordisk, Orion, Pfizer, Quintiles Switzerland Sarl, RecorMedical, Roche Diagnostics, Roche Pharma, Sahajanand IN, Sanofi, Sarstedt AG, Servier, SIS Medical, Sorin CRM SAS, SSS International Clinical Research, Stromal, Terumo Deutschland, Trama Solutions, V-Wave, Vascular Medical, Vifor, Wissens Plus, and ZOLL. Prof Ruschitzka has not received personal payments by pharmaceutical companies or device manufacturers in the last 3 years; remuneration for the time spent in the following consulting activities were made directly to the University of Zurich and do not impact on his personal remuneration: AstraZeneca (IMC), Bayer, Boehringer Ingelheim, Citi Research, Klub Class, Novo Nordisk, Radcliffe Group, Stiftung Pfizer Forschungspreis, and Vifor; remuneration for the following lectures were made directly to the University of Zurich and do not impact on his personal remuneration: Abbott, Amgen, AstraZeneca (A+ Science AB), Bayer (At the Limits), Boehringer Ingelheim, Boston Scientific (CCE Services), Brigham and Women’s Hospital Boston, C.T.I GmbH, FomF, Hôpitaux Universitaires des Genève (GECORE), Luzerner Kantonsspital, Sanofi-Aventis, Servier, Medcon, Medscape (WebMD), Medtronic, Medworld, Novartis, Roche, Ruwag, Swiss Heart Failure Academy, The Hong Kong Heart Failure Society, Trama Solutions SL, Inselspital Bern, Charité–Universitätsmedizin Berlin (Medical Education Global Solutions), Romanian Society of Cardiology, ÖKG Österreichische Gesellschaft für Kardiologie, and Zoll; has received support for attending meetings and/or travel from AstraZeneca (IMC/A+ Science AB), Boehringer Ingelheim, Centro Hospitaler de Vila Nova de Gaia, C.T.I. GmbH (Universitätsklinikum Düsseldorf), European Society of Cardiology, Monocle, Novartis, Spektar Putovanja, Austrian Heart Failure Association, and Heart Failure Association of the ESC; remuneration for following Advisory Boards were made directly to the University of Zurich and do not impact on his personal remuneration: Bayer, Roche, IMC/AstraZeneca, and Amgen; and he has received secretarial and administrative support of the HFA for his role as President/Past-President for 2018 to 2020. Dr Schunkert has received consulting fees from Amgen, Daiichi-Sankyo, Merck Sharp and Dohme, AstraZeneca, Bayer, Boehringer Ingelheim, Novartis, and Servier; has received honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events and support for attending meetings and/or travel from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi-Sankyo, Merck Sharp and Dohme, Novartis, Sanofi Aventis, Servier, and Synlab; and has received honoraria for his participation on a Data Safety Monitoring Board or Advisory Board of Boehringer Ingelheim, Daiichi-Sankyo, Novartis, and Amgen. Dr Wolfrum has received consulting fees from NVT/Biosensors as well as payments for lectures, presentations, speakers bureaus, manuscript writing, or educational events from NVT/Biosensors; and has equities in Hi-D Imaging, Winterthur, Switzerland. Dr Crea has received personal fees from Amgen, AstraZeneca, Abbott, Menarini, Chiesi, and Daiichi-Sankyo, outside of the submitted work. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The autonomic nervous system plays an important role in atrial fibrillation (AF) and hypertension. Renal denervation (RDN) lowers blood pressure (BP), but its role in AF is poorly understood., Objectives: The purpose of this study was to investigate whether RDN reduces AF recurrence after pulmonary vein isolation (PVI)., Methods: This study randomized patients from 8 centers (United States, Germany) with drug-refractory AF for treatment with PVI+RDN vs PVI alone. A multielectrode radiofrequency Spyral catheter system was used for RDN. Insertable cardiac monitors were used for continuous rhythm monitoring. The primary efficacy endpoint was ≥2 minutes of AF recurrence or repeat ablation during all follow-up. The secondary endpoints included atrial arrhythmia (AA) burden, discontinuation of class I/III antiarrhythmic drugs, and BP changes from baseline., Results: A total of 70 patients with AF (52 paroxysmal, 18 persistent) and uncontrolled hypertension were randomized (RDN+PVI, n = 34; PVI, n = 36). At 3.5 years, 26.2% and 21.4% of patients in RDN+PVI and PVI groups, respectively, were free from the primary efficacy endpoint (log rank P = 0.73). Patients with mean ≥1 h/d AA had less daily AA burden after RDN+PVI vs PVI (4.1 hours vs 9.2 hours; P = 0.016). More patients discontinued class I/III antiarrhythmic drugs after RDN+PVI vs PVI (45% vs 14%; P = 0.040). At 1 year, systolic BP changed by -17.8 ± 12.8 mm Hg and -13.7 ± 18.8 mm Hg after RDN+PVI and PVI, respectively (P = 0.43). The composite safety endpoint was not significantly different between groups., Conclusions: In patients with AF and uncontrolled BP, RDN+PVI did not prevent AF recurrence more than PVI alone. However, RDN+PVI may reduce AF burden and antiarrhythmic drug usage, but this needs further prospective validation., Competing Interests: Funding Support and Author Disclosures This study was funded by Medtronic. Dr Chinitz has received honoraria from/served as a speaker for Medtronic, Abbott, and Biotronik. Dr Böhm is supported by the Deutsche Forschungsgemeinschaft (German Research Foundation; TTR 219, project number 322900939); and has received personal fees from Abbott, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Edwards, Medtronic, Novartis, Recor, Servier, and Vifor during the conduct of the study. Dr Saba has received research support from Abbott, Boston Scientific, and Medtronic; and has served on the Advisory board of Boston Scientific and Medtronic. Dr Augostini has served on the Advisory Board of Huxley Medical; and has served as a speaker for Medtronic Corporation and Zoll Respicardia. Dr Kim, Hettrick, and Viktorova are employees at Medtronic. Dr Ukena has received honoraria for lectures and scientific advice from Aurigen Medical, Bayer, Biosense Webster, Boehringer Ingelheim, Medtronic, Pfizer, and ReCor Medical. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Patients with atrial fibrillation (AF) are at increased risk for thromboembolic events including stroke. The primary source for thromboembolism in these patients is thrombus formation in the left atrial appendage (LAA). Depending on the individual thromboembolic risk, long-term anticoagulation is recommended. In certain patients, however, long-term anticoagulation is contraindicated, and interventional closure of the LAA (LAAC) represents an alternative approach to lower the thromboembolic risk and avoid oral anticoagulation., Case Summary: An 83-year-old male underwent LAAC at our centre in November 2022. Prior to the procedure, a thrombus in the left atrium (LA) or LAA was excluded by transoesophageal echocardiography (TOE), and the anatomy of the LAA was assessed as eligible for LAAC with no evidence of anatomical irregularities. After contrast medium injection, angiography revealed an atypical anatomic variant of the LAA with a substantially long, elephant trunk-like course., Discussion: We present a previously not described unique anatomic variant of the LAA: the elephant trunk morphology. Left atrial appendage anatomy is very heterogeneous, and detailed knowledge of LAA morphology is important for endovascular LAA procedures as well as for predicting the risk of thromboembolic events. Despite thorough pre-procedural imaging, anatomic variants may remain obscured., Competing Interests: Conflict of interest: P.F. has received speaker honoraria from Astra Zeneca and Pfizer. F.M. is supported by Deutsche Gesellschaft für Kardiologie (DGK), Deutsche Forschungsgemeinschaft (SFB TRR219, Project-ID 322900939), and Deutsche Herzstiftung. Saarland University has received scientific support from Ablative Solutions, Medtronic and ReCor Medical. Until May 2024, F.M. has received speaker honoraria/consulting fees from Ablative Solutions, Amgen, Astra-Zeneca, Bayer, Boehringer Ingelheim, Inari, Medtronic, Merck, ReCor Medical, Servier, and Terumo. M.B. reports personal fees from Abbott, Amgen, Astra Zeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Medtronic, Novartis, Servier, and Vifor. C.U. has received speaker horonaria/consulting fees from Aurigen, Bayer, Biosense Webster, Bristol Myers Squibb, Medtronic, Pfizer, and Recor Medical., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: During the SARS-CoV-2 pandemic it was speculated that the virus might be associated with a persistent increase of cardiovascular risk. The present study compares pre- and post-pandemic hospital admission rates for hypertension and coronary artery disease., Methods: Systematic multicentric retrospective cohort analysis of 57.795 hospital admissions in an urban region in Germany during two different periods (pre-pandemic 01-06/2019 vs. post-pandemic era 01-06/2023). Information on hospital admissions for arterial hypertension, chronic coronary syndrome, unstable angina pectoris and acute myocardial infarction were extracted from the hospitals data systems. Additionally, six comorbidities and performed coronary interventions were monitored., Results: Compared to the pre-pandemic era, there was no increase in hospitalizations for arterial hypertension (516 vs. 483, -6.8%, p  = 0.07) or myocardial infarction (487 vs. 349, -23.8%, p  < 0.001), but the total number of patient admissions with chest pain as the presenting symptom increased (chronic coronary syndrome: 759 vs. 943, +24.2%, p  < 0.001; unstable angina pectoris: 270 vs. 451, +67.0%, p  < 0.001). At the same time, the number of performed coronary angiographies increased, but less patients underwent percutaneous interventions. Patients admitted with chest pain in the post-pandemic era were in general healthier with less comorbidities., Conclusion: The present multicenter cohort study found no evidence for an increase in hospitalizations for arterial hypertension or coronary artery disease after the end of the pandemic. However, further studies with larger sample sizes are needed to confirm our results., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (© 2024 Sasko, Matiakis, Seibert, Pagonas, Hippe, Babel, Ukena and Westhoff.)

Background: In the OptiLink heart failure study, timely and appropriate reactions to telemedicine alerts improved clinical outcomes in heart failure patients. This analysis investigates the relation between the weekday of alert transmission and the subsequent patient contact., Methods: In patients enrolled in the intervention arm of the OptiLink heart failure study ( n  = 505, age 66.1 ± 10.1, 77.2% male, left-ventricular ejection fraction 26.7% ± 6.1%), fluid index threshold crossing alerts were analysed according to the weekday of the transmission. Transmissions on Mondays-Thursdays were categorized as TD1, Fridays-Sundays as well as public holidays as TD2., Results: Of 1365 transmitted alerts, 867 (63.5%) were categorized as TD1 and 498 (36.5%) as TD2. Same day telephone contacts were more frequent in TD1 (46.2%) than in TD2 (18.3%; p  < 0.001). Accordingly, the median time to contact was significantly longer in TD2 compared with TD1 (2(1-3) vs 0(0-1) days; p  < 0.001). Rates of no telephone contact were no different between the groups (12.1% vs 12.4%; p  = 0.866). Although signs of worsening heart failure were prevalent in 32.4% in TD1 versus 32.1% in TD2 ( p  = 0.996), initiation of a pharmacological intervention occurred more likely in TD1 compared with TD2 (27.9% vs 22.9%; p  = 0.041). No differences existed concerning hospitalization for heart failure within 30 days after alert transmission (3.9% vs 3.4%; p  = 0.636)., Conclusion: Alert transmissions during weekends and public holidays were less likely associated with timely patient contacts and initiation of pharmacological interventions than during the week. Telemedical centres providing 24/7 remote monitoring service and specific education programmes for physicians might help to optimize patient care., Competing Interests: Declaration of conflicting interestsJB, RB, HO, CB and KR have all received grant support from Medtronic. VP has received honoraria from Bayer. MB has received lecture honoraria and consulting fees from Amgen, Abbott, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Medtronic, Novartis, Servier and Vifor. FM has received scientific support and speaker honoraria from Bayer, Boehringer Ingelheim, Medtronic and ReCor Medical. JW and CU have received lecture honoraria from Bristol Myers Squibb. DM has no relationships relevant to the contents of this paper to disclose.

Aims: Takotsubo syndrome (TTS) is associated with a substantial rate of adverse events. We sought to design a machine learning (ML)-based model to predict the risk of in-hospital death and to perform a clustering of TTS patients to identify different risk profiles., Methods and Results: A ridge logistic regression-based ML model for predicting in-hospital death was developed on 3482 TTS patients from the International Takotsubo (InterTAK) Registry, randomly split in a train and an internal validation cohort (75% and 25% of the sample size, respectively) and evaluated in an external validation cohort (1037 patients). Thirty-one clinically relevant variables were included in the prediction model. Model performance represented the primary endpoint and was assessed according to area under the curve (AUC), sensitivity and specificity. As secondary endpoint, a K-medoids clustering algorithm was designed to stratify patients into phenotypic groups based on the 10 most relevant features emerging from the main model. The overall incidence of in-hospital death was 5.2%. The InterTAK-ML model showed an AUC of 0.89 (0.85-0.92), a sensitivity of 0.85 (0.78-0.95) and a specificity of 0.76 (0.74-0.79) in the internal validation cohort and an AUC of 0.82 (0.73-0.91), a sensitivity of 0.74 (0.61-0.87) and a specificity of 0.79 (0.77-0.81) in the external cohort for in-hospital death prediction. By exploiting the 10 variables showing the highest feature importance, TTS patients were clustered into six groups associated with different risks of in-hospital death (28.8% vs. 15.5% vs. 5.4% vs. 1.0.8% vs. 0.5%) which were consistent also in the external cohort., Conclusion: A ML-based approach for the identification of TTS patients at risk of adverse short-term prognosis is feasible and effective. The InterTAK-ML model showed unprecedented discriminative capability for the prediction of in-hospital death., (© 2023 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Objective: Dietary sodium intake represents a risk factor for cardiovascular disease and mortality. The study sought to analyse the sodium content of effervescent dietary supplements and drugs in Germany and the USA., Design: Comparative cross-sectional study., Setting and Methods: The sodium content of 39 dietary supplement effervescent tablets available in Germany was measured in May and June 2022 using optical emission spectrometry with inductively coupled argon plasma. The sodium content of 33 common pharmacy-only effervescent tablets (over-the-counter (OTC) drugs) in Germany was obtained from the summary of product characteristics. We compared the sodium content of the measured German dietary supplement effervescent tablets to that of 51 dietary supplement effervescent tablets available in the USA (data: National Institutes of Health's Dietary Supplement Label Database)., Results: The measured sodium content in the German dietary supplements was 283.9±122.6 mg sodium/tablet, equivalent to 14±6% of the maximum recommended daily sodium intake (MRDSI). Vitamin products had the highest (378.3±112.8 mg, 19±6% of MRDSI), and calcium products had the lowest mean sodium content (170.4±113.2 mg, 9±6% of MRDSI). Vitamin products contained significantly more sodium than magnesium (378.3 mg vs 232.7 mg; p=0.004), calcium (378.3 mg vs 170.4 mg; p=0.006) and mineral products (378.3 mg vs 191.6 mg; p=0.048). The sodium content measured in products available in Germany was higher when compared with the declared sodium content on the label of the products sold in the USA (283.9 mg vs 190.0 mg; p<0.001). The median summary of product characteristics-declared sodium content of a single dose of the German OTC drugs was 157.0 mg (IQR: 98.9-417.3 mg); pain/common cold drugs contained the most sodium (median: 452.1 mg; IQR: 351.3-474.0 mg)., Conclusion: Effervescent tablets of nutritional supplements and OTC drugs contain high amounts of sodium, which often is not disclosed., Competing Interests: Competing interests: MB is supported by the Deutsche Forschungsgemeinschaft (German Research Foundation; TTR 219, project number 322900939) and reports personal fees from Abbott, Amgen, AstraZeneca, Bayer, Boehringer-Ingelheim, Cytokinetic, Edwards, Medtronic, Novartis, ReCor Medical, Servier and Vifor. FM is supported by Deutsche Gesellschaft für Kardiologie (DGK), Deutsche Forschungsgemeinschaft (SFB TRR219) and Deutsche Herzstiftung and has received scientific support and/or speaker honoraria from AstraZeneca, Bayer, Boehringer Ingelheim, Medtronic, Merck and ReCor Medical. LL has received speaker honoraria from ReCor Medical and Medtronic. CU has received lecture honoraria or consulting fees from Bayer, Bristol Myers Squibb, Medtronic and ReCor Medical. UL has received speaker honoraria from Amgen, Daiichi Sankyo, Novartis and Sanofi, all outside the submitted work. MS has received speaker honoraria from BMS, Daiichi Sankyo, DGK-Academy, Pfizer and Sanofi and consulting fees from CSL Vifor, MSD and Novartis, all outside the submitted work. FG is supported by German Foundation for Heart Research (Deutsche Herzstiftung) and has received speaker honoraria from AstraZeneca. The other authors do not have conflicts of interest., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Novel pacing technologies, such as His bundle pacing (HBP) and left bundle branch area pacing (LBBaP), have emerged to maintain physiological ventricular activation. We investigated the outcomes of LBBP with HBP for patients requiring a de novo permanent pacing., Methods and Results: Systematic review of randomized clinical trials and observational studies comparing LBBaP with HBP until March 01, 2023 was performed. Random and fixed effects meta-analyses of the effect of pacing technology on outcomes were performed. Study outcomes included pacing metrics, QRS duration, lead revision, procedure parameters, all-cause mortality and heart failure hospitalization (HFH). Overall, 10 studies with 1596 patients were included. Implant success rate was higher in LBBaP compared with HBP (RR 1.24, 95% CI: 1.08 to 1.42, p = .002). LBBaP was associated with lower capture threshold at implantation (mean difference (MD) -0.62 V, 95% CI: -0.74 to -0.51 V, p < .0001) and at follow-up (MD -0.74 V, 95% CI: -0.96 to -0.53, p < .0001), shorter procedure duration (MD -14.66 min, 95% CI: -23.54 to -5.78, p = .001) and shorter fluoroscopy time (MD -4.2 min, 95% CI: -8.4 to -0.0, p = .05). Compared with HBP, LBBaP was associated with a decreased risk of all-cause mortality (RR: 0.50, 95% CI: 0.33 to 0.77, p = .002) and HFH (RR: 0.57, 95% CI: 0.33 to 1.00, p = .05). No statistical differences were found in lead revisions and QRS duration before and after pacing., Conclusion: This meta-analysis found that LBBaP was superior to HBP regarding pacing metrics and implant success rate as an initial pacing strategy, although absence of head-to-head randomized comparison warrants caution in interpretation of the results., (© 2023 The Authors. Pacing and Clinical Electrophysiology published by Wiley Periodicals LLC.)

Background and Aims: Pharmacovigilance reports, associating hydrochlorothiazide (HCT) with skin cancer, resulted in a significant decrease of HCT prescriptions for hypertension and heart failure. Whether HCT exhibits phototoxic properties thereby causing skin cancer remains unknown. This study aimed to examine the photosensitizing, phototoxic and carcinogenic potential of HCT in a randomized, placebo-controlled, double-blind trial in vivo and also in vitro ., Methods: The trial assigned 30 healthy, normotensive adult volunteers in a 2:1 ratio to either HCT 25 mg/day or placebo for 15 days. Photosensitivity of the skin with and without the effect of HCT treatment were assessed. Following whole-body ultraviolet A (UVA) and B (UVB, 311 nm) irradiation, phototoxic and carcinogenic reactions by measuring urinary excretion of pyrimidine dimers were evaluated. For the in-vitro studies, human keratinocytes (HaCaT) were incubated with HCT, irradiated with UVB, and analysed for markers of inflammation, apoptosis and carcinogenesis., Results: Skin photosensitivity following exposure to UVA and UVB remained unchanged from baseline to 15-day follow-up in both groups (UVA change HCT 0.0 J/cm 2 vs. placebo 0.0 J/cm 2 ; P  = 0.99; UVB change HCT 0.0 J/cm 2 vs. placebo -0.2 J/cm 2 ; P  = 0.06). Pyrimidine dimers were not detected in either group. In vitro , combination of HCT and UVB irradiation did not induce the expression of oxidative stress marker proteins, inflammatory proteins, apoptotic proteins or activation of oncoproteins., Conclusion: HCT did not increase photosensitivity for UVA or UVB in healthy volunteers compared with placebo, and was not associated with phototoxic or carcinogenic reactions. In vitro , HCT was also not associated with phototoxicity or carcinogenesis (NCT04654312)., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Aims: Remote monitoring (RM) of thoracic impedance represents an early marker of pulmonary congestion in heart failure (HF). Chronic kidney disease (CKD) may promote fluid overload in HF patients. We investigated whether concomitant CKD affected the efficacy of impedance-based RM in the OptiLink HF trial., Methods and Results: Among HF patients included in the OptiLink HF trial, time to the first cardiovascular hospitalization and all-cause death according to the presence of concomitant CKD was analysed. CKD was defined as GFR < 60 mL/min/1.73 m 2 at enrolment. Of the 1002 patients included in OptiLink HF, 326 patients (33%) had HF with concomitant CKD. The presence of CKD increased transmission of telemedical alerts (median of 2 (1-5) vs. 1 (0-3); P = 0.012). Appropriate contacting after alert transmission was equally low in patients with and without CKD (57% vs. 59%, P = 0.593). The risk of the primary endpoint was higher in patients with CKD compared with patients without CKD (hazard ratio (HR), 1.62 [95% confidence interval (CI), 1.16-2.28]; P = 0.005). Impedance-based RM independently reduced primary events in HF patients with preserved renal function, but not in those with CKD (HR 0.68 [95% CI, 0.52-0.89]; P = 0.006)., Conclusions: The presence of CKD in HF patients led to a higher number of telemedical alert transmissions and increased the risk of the primary endpoint. Inappropriate handling of alert transmission was commonly observed in patients with chronic HF and CKD. Guidance of HF management by impedance-based RM significantly decreased primary event rates in patients without CKD, but not in patients with CKD., (© 2023 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Aim: Transcatheter aortic valve replacement (TAVR) can cause intraventricular conduction disturbances (ICA), particularly left bundle branch block (BBB) and high-degree atrioventricular block (HAVB). The aim of this study was to investigate clinical, anatomical, procedural, and electrophysiological parameters predicting ICA after TAVR., Methods: Patients with severe aortic stenosis (n = 203) without pacing devices undergoing TAVR with a self-expanding (n = 103) or balloon-expanding (n = 100) valve were enrolled. Clinical and anatomical parameters, such as length of the membranous septum (MS) and implantation depth, were assessed. His-ventricular interval (HVi) before and after implantation was determined. 12-lead-electrocardiograms (ECG) before, during and after 3 and 30 days after TAVR were analyzed for detection of any ICA., Results: Among 203 consecutive patients (aortic valve area 0.78 ± 0.18 cm 2 , age 80 ± 6 years, 54% male, left ventricular ejection fraction 52 ± 10%), TAVR led to a significant prolongation of infranodal conduction in all patients from 49 ± 10 ms to 59 ± 16 ms (p = 0.01). The HVi prolongation was independent of valve types, occurrence of HAVB or ICA. Fifteen patients (7%) developed HAVB requiring permanent pacemaker (PPM) implantation and 63 patients (31%) developed ICA within 30 days. Pre-existing BBB (OR 11.64; 95% CI 2.87-47.20; p = 0.001), new-onset left BBB (OR 15.72; 95% CI 3.05-81.03; p = 0.001), and diabetes mellitus (OR 3.88; 95% CI 1.30-15.99; p = 0.02) independently predicted HAVB requiring PPM. Neither pre-existing right BBB, a prolonged postHVi, increases in PR duration, any of the TAVR implantation procedural and anatomic nor echocardiographic characteristics were predictive for later HAVB., Conclusions: New-onset left BBB and diabetes mellitus independently predicted HAVB requiring PPM after TAVR and helped to identify patients at risk. Electrophysiologic study (EPS) of atrioventricular conduction was neither specific nor predictive of HAVB and can be skipped., Trial Registration Number: NCT04128384 ( https://www., Clinicaltrials: gov )., (© 2023. The Author(s).)

Background To analyze the quantity and impact of cardiovascular research done in Africa or coauthored by researchers based in Africa, their determinants, and the patterns of research collaboration. Methods and Results We retrieved data from Web of Science and additional sources. We analyzed temporal trends from 1971 to 2021 and geographical distribution, research impact using country-level h-index, international research cooperation, and associations of research quantity and quality using linear regression. The annual volume of cardiovascular research from Africa has increased from 4 publications in 1971 to 3867 in 2020 and currently represents ~3% of the global cardiovascular research output. Authors from South Africa (28.1%) and Egypt (24.1%) accounted for more than half of all publications from African countries, and they had the highest h-index (209 and 111, respectively). Important collaborators outside Africa included the United States, United Kingdom, France, Germany, and Australia. The country's publication count was associated with larger population size ( P <0.001), whereas the country's h-index was associated with larger population size ( P =0.001) and higher human development index ( P =0.023). International collaboration was dominated by the United States, South Africa, United Kingdom, Egypt, and Canada. The level of collaboration between African countries was lower than their collaboration with non-African countries. Conclusions Cardiovascular research output from African authors remains low, despite marked progress over the past 5 decades. These findings highlight the urgent need to improve the quantity and quality of cardiovascular research in Africa through increased investments, training of human resources, improved infrastructures, and expansion of collaborative research networks, particularly within Africa.

Background: Catheter-based renal denervation (RD), in addition to pulmonary vein isolation (PVI), reduces atrial fibrillation (AF) recurrence in hypertensive patients. Whether RD, without additional PVI, can prevent subclinical atrial fibrillation (SAF) in patients with hypertensive heart disease (HHD) is unknown., Objective: The purpose of this study was to assess the efficacy of RD in preventing SAF in patients with HHD., Methods: A single-center, randomized, sham-controlled pilot trial, including patients >55 years in sinus rhythm, but with a high risk of developing SAF was conducted. Patients had uncontrolled hypertension despite taking 3 antihypertensive drugs, including a diuretic. The primary endpoint was the first SAF episode lasting ≥6 minutes recorded via an implantable cardiac monitor scanned every 6 months for 24 months. A blinded independent monitoring committee assessed electrocardiographic rhythm recordings. Change in SAF burden (SAFB), and office and 24-hour ambulatory blood pressure (BP) at 6-month follow-up were secondary endpoints., Results: Eighty patients were randomly assigned to RD (n = 42) or sham groups (n = 38). After 24 months of follow-up, SAF occurred in 8 RD patients (19%) and 15 sham patients (39.5%) (hazard ratio 0.40; 95% confidence interval 0.17-0.96; P = .031). Median [interquartile range] SAFB was low in both groups but was significantly lower in the RD vs sham group (0% [0-0] vs 0% [0-0.3]; P = .043). Fast AF (>100 bpm) occurred less frequently in the RD than sham group (2% vs 26%; P = .002). After adjusting for baseline values, there were no significant differences in office or 24-hour BP changes between treatment groups., Conclusion: RD reduced incident SAF events, SAFB, and fast AF in patients with HHD. The observed effects may occur independent of BP lowering., (Copyright © 2022 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Right ventricular pacing (RVP) may cause electrical and mechanical desynchrony leading to impaired left ventricular ejection fraction (LVEF). We investigated the outcomes of RVP with His bundle pacing (HBP) and left bundle branch pacing (LBBP) for patients requiring a de novo permanent pacemaker (PPM) for bradyarrhythmia., Methods and Results: Systematic review of randomized clinical trials and observational studies comparing HBP or LBP with RVP for de novo PPM implantation between 01 January 2013 and 17 November 2020 was performed. Random and fixed effects meta-analyses of the effect of pacing technology on outcomes were performed. Study outcomes included all-cause mortality, heart failure hospitalization (HFH), LVEF, QRS duration, lead revision, atrial fibrillation, procedure parameters, and pacing metrics. Overall, 9 studies were included (6 observational, 3 randomised). HBP compared with RVP was associated with decreased HFH (risk ratio [RR] 0.68, 95% confidence interval [CI] 0.49-0.94), preservation of LVEF (mean difference [MD] 0.81, 95% CI - 1.23 to 2.85 vs. - 5.72, 95% CI - 7.64 to -3.79), increased procedure duration (MD 15.17 min, 95% CI 11.30-19.04), and increased lead revisions (RR 5.83, 95% CI 2.17-15.70, p = 0.0005). LBBP compared with RVP was associated with shorter paced QRS durations (MD 5.6 ms, 95% CI - 6.4 to 17.6) vs. (51.0 ms, 95% CI 39.2-62.9) and increased procedure duration (MD 37.78 min, 95% CI 20.04-55.51)., Conclusion: Of the limited studies published, this meta-analysis found that HBP and LBBP were superior to RVP in maintaining physiological ventricular activation as an initial pacing strategy., (© 2021. The Author(s).)

Aims: Differentiation of left ventricular (LV) hypertrophy in healthy athletes from pathological LV hypertrophy in heart disease is often difficult. We explored whether extended echocardiographic measurements such as E/e' and global longitudinal strain (GLS) distinguish physiologic from maladaptive hypertrophy in hypertrophic cardiomyopathy, excessively trained athletes' hearts and normal hearts., Methods: Seventy-eight professional athletes (cyclists n = 37, soccer players n = 29, handball players n = 21) were compared with patients (n = 88) with pathological LV hypertrophy (hypertrophic obstructive cardiomyopathy (HOCM, n = 17), hypertensive heart disease (HHD, n = 36), severe aortic valve stenosis (AVS, n = 35) and with sedentary healthy individuals as controls (n = 37)., Results: LV ejection fraction (LVEF) was ≥50% in all patients, athletes (median age 26 years, all male) and the controls (97% male, median age 32 years). LV mass index (LVMI) and septal wall thickness was in normal range in controls, but elevated in cyclists and patients with pathological hypertrophy (p < 0.001 for both). E/e' was elevated in all patients with maladaptive hypertrophy but normal in controls and athletes (p < 0.001 vs. pathological hypertrophy). Furthermore GLS was reduced in patients with pathological hypertrophy compared with athletes and controls (for both p < 0.001). In subjects with septal wall thickness >11 mm, GLS (≥-18%) has a specificity of 79% to distinguish between physiological and pathological hypertrophy., Conclusion: GLS and E/e' are reliable parameters unlike left ventricular mass or LV ejection fraction to distinguish pathological and physiological hypertrophy., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: L.L. received speaker honoraria from Medtronic and ReCor Medical, outside the submitted work. M.B. reports support from Abbott, Amgen, Astra-Zeneca, Bayer, Boehringer-Ingelheim, Medtronic, Novartis, Recor, Servier, and Vifor outside the submitted work. All other authors have declared no conflict of interest. S.E. received speakers or consultant honorarium and/or travel support from Medtronic, Recor, Bayer, Daiichi Sankyo, Böhringer Ingelheim, Novartis, AstraZeneca, Akcea Therapeutics and Bristol-Myers Squibb-Pfizer., (© 2022 Published by Elsevier B.V.)

Background: Atrial fibrillation (AF) represents a frequent complication in patients after interventional closure of patent foramen ovale (PFO). We aimed to compare the incident rate and risk of AF between Amplatzer PFO and GORE (Helex and CARDIOFORM Septal Occluder) device by analyzing the data from randomized trials., Methods: We included all randomized studies which reported the rate of AF after PFO closure using Amplatzer or GORE occluder in patients suffering cryptogenic stroke and compared the risk of AF between the two devices. PubMed and Cochrane library were searched for eligible studies published until July 2020., Results: Rate of all cases of incident AF from randomized trials with Amplatzer in the interventional group was 3.93% (30/763) vs. 1.46% (11/751) in the respective medical group (RR of 2.57, 95% CI 1.31-5.03, p = 0.006). The incidence of incident AF from randomized trial with GORE device was 6.57% (29/441) vs. 0.44% (1/223) in the respective medical group (RR of 14.66, 95% CI 2.01-106.95, p = 0.008). The p for interaction between the two devices regarding risk of AF was 0.10., Conclusions: The results suggest lower risk expressed by lower rate of incident AF after PFO closure using Amplatzer PFO Occluder when compared with GORE Occluder. However, these findings are derived from secondary analyses and should be scrutinized using appropriate screening tool for AF following PFO closure in adequately powered randomized clinical trial with a head-to-head design that compares the two devices., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background: Stroke is the second leading cause of death world-wide. A comprehensive scientometric study regarding ischemic stroke research has not been performed yet. This study aims at investigating the global research output on ischemic stroke research., Methods: All 21,115 articles regarding ischemic stroke were retrieved from the Web-of-Science-Core-Collection and analyzed regarding regional differences, the authors' sex, subtopics of stroke, as well as international research collaborations., Results: A total of 132 different countries participated, with the USA contributing most publications with 4,614 (21.9%), followed by China with 3,872 (18.3%), and Germany with 1,120 (5.3%). Analyzing the scientific quality of different countries by H-index, the USA ranked first with an H-index of 202, followed by Germany (H-index 135) and the United Kingdom (UK;H-index 129). The most frequently used topic was "Clinical Neurology" with 9,028 publications. Among all first authors attributed to their sex, 32.3% of all first authors were female and 67.7% were male (4,335 vs. 9,097). The proportion of female last authors was comparatively lower at 22.4% (3,083 publications) compared with 77.6% male authors (10,658 publications). There was a broad network of international collaborations., Conclusions: Research in ischemic stroke has substantially increased over time. Scientists from the USA have the highest number of publications, followed by China and Germany. Measured by the H-index, the USA held the highest publication quality, followed by Germany and the UK. The scientific landscape was male-dominated with 67.7% of all first authors being male. Worldwide international collaborations play a major role in ischemic stroke research., Competing Interests: DM has received honoraria from Bayer, Boston Scientific, and Daiichi Sankyo. MB receives honoraria for lectures and scientific advice from Abbott, Astra-Zeneca, Boehringer-Ingelheim, Medtronic, Novartis, Servier, and Vifor. FM has received scientific support and speaker honoraria from Bayer, Boehringer Ingelheim, Medtronic, and ReCor Medical. CU received scientific support and speaker honorarium from Bayer, Boehringer-Ingelheim, Medtronic Inc., Recor Medical, and Pfizer. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Millenaar, Ragoschke-Schumm, Fehlmann, Raible, Lochner, Böhm, Fassbender, Keller, Mahfoud and Ukena.)

(1) Background: Atrial fibrillation (AF) is associated with anxiety, depression, and chronic stress, and vice versa. The purpose of this study was to evaluate potential effects of pulmonary vein isolation (PVI) on psychological factors. (2) Methods: Psychological assessment was performed before PVI as well as after six months. (3) Results: A total of 118 patients [age 64 ± 9 years, 69% male, left ventricular ejection fraction 57 ± 8%, 56% paroxysmal AF] undergoing PVI were included. After PVI, significant improvements were observed in the mean total heart-focused anxiety (HFA) score, as well as in the Cardiac Anxiety Questionnaire (CAQ) sub-scores: HFA attention, HFA fear, and HFA avoidance scores. Subgroup analyses showed an association of improvement with freedom of documented AF recurrence. Mean scores of general anxiety and depression evaluated by the Hospital Anxiety and Depression Scale (HADS) decreased significantly after PVI in all subgroups regardless of AF recurrence. Further, both physical and mental composite scores of the Short Form Health Survey (SF-12) increased significantly from baseline. (4) Conclusions: PVI results in a significant reduction in HFA. Improvements in general anxiety and depressive symptoms did not seem to be related only to rhythm control per se. Therefore, CAQ may represent a more specific evaluation tool as HADS in patients with AF.

Background: In patients with chronic kidney disease (CKD), atrial fibrillation (AF) is highly prevalent and represents a major risk factor for stroke and death. CKD is associated with atrial proarrhythmic remodeling and activation of the sympathetic nervous system. Whether reduction of the sympathetic nerve activity by renal denervation (RDN) inhibits AF vulnerability in CKD is unknown., Methods: Left atrial (LA) fibrosis was analyzed in samples from patients with AF and concomitant CKD (estimated glomerular filtration rate [eGFR], <60 mL/min per 1.73 m 2 ) using picrosirius red and compared with AF patients without CKD and patients with sinus rhythm with and without CKD. In a translational approach, male Sprague Dawley rats were fed with 0.25% adenine (AD)-containing chow for 16 weeks to induce CKD. At week 5, AD-fed rats underwent RDN or sham operation (AD). Rats on normal chow served as control. After 16 weeks, cardiac function and AF susceptibility were assessed by echocardiography, radiotelemetry, electrophysiological mapping, and burst stimulation, respectively. LA tissue was histologically analyzed for sympathetic innervation using tyrosine hydroxylase staining, and LA fibrosis was determined using picrosirius red., Results: Sirius red staining demonstrated significantly increased LA fibrosis in patients with AF+CKD compared with AF without CKD or sinus rhythm. In rats, AD demonstrated LA structural changes with enhanced sympathetic innervation compared with control. In AD, LA enlargement was associated with prolonged duration of induced AF episodes, impaired LA conduction latency, and increased absolute conduction inhomogeneity. RDN treatment improved LA remodeling and reduced LA diameter compared with sham-operated AD. Furthermore, RDN decreased AF susceptibility and ameliorated LA conduction latency and absolute conduction inhomogeneity, independent of blood pressure reduction and renal function., Conclusions: In an experimental rat model of CKD, RDN inhibited progression of atrial structural and electrophysiological remodeling. Therefore, RDN represents a potential therapeutic tool to reduce the risk of AF in CKD, independent of changes in renal function and blood pressure.

The clinical implications of hypertension in addition to a high prevalence of both uncontrolled blood pressure and medication nonadherence promote interest in developing device-based approaches to hypertension treatment. The expansion of device-based therapies and ongoing clinical trials underscores the need for consistency in trial design, conduct, and definitions of clinical study elements to permit trial comparability and data poolability. Standardizing methods of blood pressure assessment, effectiveness measures beyond blood pressure alone, and safety outcomes are paramount. The Hypertension Academic Research Consortium (HARC) document represents an integration of evolving evidence and consensus opinion among leading experts in cardiovascular medicine and hypertension research with regulatory perspectives on clinical trial design and methodology. The HARC document integrates the collective information among device-based therapies for hypertension to better address existing challenges and identify unmet needs for technologies proposed to treat the world's leading cause of death and disability. Consistent with the Academic Research Consortium charter, this document proposes pragmatic consensus clinical design principles and outcomes definitions for studies aimed at evaluating device-based hypertension therapies.

Background We sought to investigate sex-specific differences in authorship of cardiovascular research over the past decade. Methods and Results All 387 463 cardiovascular publications between 2010 and 2019 were retrieved from Web of Science. Articles increased from 19 960 to 29 604 articles per year ( P >0.001). The number of articles written by female first authors increased by 76.3% (6434-11 343 articles) and by 35.0% for male first authors (13 526-18 261) ( P <0.001). The first author was more likely to be a female author in articles with female last authors. The median impact factor (IF) for articles by female first authors was lower (2.46 [interquartile range, 7 1.11-4.03] versus 2.51 [interquartile range, 1.17-4.10]; P <0.001). Female authorship articles reached the highest IF in North America (average IF, 3.7), with the lowest in Africa (average IF, 1.8). Conclusions Publications in cardiovascular research have increased over the past decade, particularly by female authors. Female researchers are cited less often compared with their male peers. The IF remains lower for articles by female researchers.

Background: Previous studies established a role for the wearable cardioverter defibrillator (WCD) to effectively and safely bridge temporary risk for sudden cardiac death (SCD) in patients with advanced heart failure. The prognostic relevance of the WCD remains controversial., Objectives: The authors investigated adherence to, as well as the safety and effectiveness of, WCD use in a real-world cohort of patients at high risk for SCD., Material and Methods: All consecutive patients (n = 83) receiving a WCD at a German tertiary care hospital between April 2012 and December 2019 were retrospectively included in this analysis. Patient characteristics were collected at the time of the index hospitalization. Using the Zoll® lifeVest® (ZOLL Medical Corporation, Chelmsford, MA, USA) network database, two separate investigators evaluated adherence to the WCD as well as arrhythmic events during WCD wear time., Results: During 3680 wearing days (mean WCD wear time, 44 days) with a median daily wear time of 23.1 h, three arrhythmic events of relevance (sustained ventricular tachycardia, VT) occurred, one of which was sufficiently terminated by WCD shock. Another patient died from sudden cardiac death while pausing his WCD. Right bundle branch block correlated significantly with sustained VT occurrence (r = 0.3315; 95% CI -0.1265 to 0.3014; p = 0.0022). In 30 patients (36.1%) a cardioverter/defibrillator was implanted., Conclusion: In a real-life clinical setting, the use of WCD in patients at high risk for sudden cardiac death is effective and safe and adherence to the device is high. The event rate for VA was lower than in comparable patient cohorts. Adherence remains a crucial issue as one patient in the present series died while not wearing the device., (© 2021. Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Background: Ethnic disparities have been reported in cardiovascular disease. However, ethnic disparities in takotsubo syndrome (TTS) remain elusive. This study assessed differences in clinical characteristics between Japanese and European TTS patients and determined the impact of ethnicity on in-hospital outcomes., Methods: TTS patients in Japan were enrolled from 10 hospitals and TTS patients in Europe were enrolled from 32 hospitals participating in the International Takotsubo Registry. Clinical characteristics and in-hospital outcomes were compared between Japanese and European patients., Results: A total of 503 Japanese and 1670 European patients were included. Japanese patients were older (72.6 ± 11.4 years vs. 68.0 ± 12.0 years; p < 0.001) and more likely to be male (18.5 vs. 8.4%; p < 0.001) than European TTS patients. Physical triggering factors were more common (45.5 vs. 32.0%; p < 0.001), and emotional triggers less common (17.5 vs. 31.5%; p < 0.001), in Japanese patients than in European patients. Japanese patients were more likely to experience cardiogenic shock during the acute phase (15.5 vs. 9.0%; p < 0.001) and had a higher in-hospital mortality (8.2 vs. 3.2%; p < 0.001). However, ethnicity itself did not appear to have an impact on in-hospital mortality. Machine learning approach revealed that the presence of physical stressors was the most important prognostic factor in both Japanese and European TTS patients., Conclusion: Differences in clinical characteristics and in-hospital outcomes between Japanese and European TTS patients exist. Ethnicity does not impact the outcome in TTS patients. The worse in-hospital outcome in Japanese patients, is mainly driven by the higher prevalence of physical triggers., Trial Registration: URL: https://www.clinicaltrials.gov ; Unique Identifier: NCT01947621., (© 2021. The Author(s).)

Background: Cardiac autonomic dysfunction after myocardial infarction identifies patients at high risk despite only moderately reduced left ventricular ejection fraction. We aimed to show that telemedical monitoring with implantable cardiac monitors in these patients can improve early detection of subclinical but prognostically relevant arrhythmic events., Methods: We did a prospective investigator-initiated, randomised, multicentre, open-label, diagnostic trial at 33 centres in Germany and Austria. Survivors of acute myocardial infarction with left ventricular ejection fraction of 36-50% had biosignal analysis for assessment of cardiac autonomic function. Patients with abnormal periodic repolarisation dynamics (≥5·75 deg 2 ) or abnormal deceleration capacity (≤2·5 ms) were randomly assigned (1:1) to telemedical monitoring with implantable cardiac monitors or conventional follow-up. Primary endpoint was time to detection of serious arrhythmic events defined by atrial fibrillation 6 min or longer, atrioventricular block class IIb or higher and fast non-sustained (>187 beats per min; ≥40 beats) or sustained ventricular tachycardia or fibrillation. This study is registered with ClinicalTrials.gov, NCT02594488., Findings: Between May 12, 2016, and July 20, 2020, 1305 individuals were screened and 400 patients at high risk were randomly assigned (median age 64 years [IQR 57-73]); left ventricular ejection fraction 45% [40-48]) to telemedical monitoring with implantable cardiac monitors (implantable cardiac monitor group; n=201) or conventional follow-up (control group; n=199). During median follow-up of 21 months, serious arrhythmic events were detected in 60 (30%) patients of the implantable cardiac monitor group and 12 (6%) patients of the control group (hazard ratio 6·33 [IQR 3·40-11·78]; p<0·001). An improved detection rate by implantable cardiac monitors was observed for all types of serious arrhythmic events: atrial fibrillation 6 min or longer (47 [23%] patients vs 11 [6%] patients; p<0·001), atrioventricular block class IIb or higher (14 [7%] vs 0; p<0·001) and ventricular tachycardia or ventricular fibrillation (nine [4%] patients vs two [1%] patients; p=0·054)., Interpretation: In patients at high risk after myocardial infarction and cardiac autonomic dysfunction but only moderately reduced left ventricular ejection fraction, telemedical monitoring with implantable cardiac monitors was highly effective in early detection of subclinical, prognostically relevant serious arrhythmic events., Funding: German Centre for Cardiovascular Research (DZHK) and Medtronic Bakken Research Center., Competing Interests: Declaration of interests AB received funding from Medtronic Bakken Research Center as co-funding for the SMART-MI trial (providing implantable cardiac monitors and staff cost for implantable cardiac monitors core lab); and speaker honoraria from Bayer, Boerhinger Ingelheim, Edwards, Medtronic, and Novartis. MSt received consulting fees, speaker honoraria, and travel expenses from Medtronic. RW received grants from German Centre for Cardiovascular Research, Bristol Myers Squibb–Pfizer, and Grant Boston Scientific; speaker honoraria from Biotronik, Boston Scientific, Medtronic, Abiomed, Bristol Myers Squibb–Pfizer, Boehringer Ingelheim, Daiichi Sankyo, Bayer, and Novartis; and travel expenses from Boston Scientific, Bristol Myers Squibb–Pfizer, Boehringer Ingelheim, Daiichi Sankyo, and Bayer. RW participated on advisory boards for Biotronik, Philips, Boehringer Ingelheim, and Daiichi Sankyo. ALu received grants and consulting fees from Boston Scientific and Biosense Webster; speaker honoraria from Boston Scientific, Biosense Webster, and Medtronic; travel expenses from Boston Scientific; and participated on data safety monitoring boards and societies for Boston Scientific. NG received grants from Boston Scientific and Medtronic and travel expenses from Bayer Vital. PC received research grants from Philips. LSM received grants from the German Research Foundation and the EU; speaker honoraria from Bayer, Astra Zeneca, Pfizer, Bristol Myers Squibb, Daiichi Sankyo, and Boehringer Ingelheim; travel expenses from Servier, Boehringer Ingelheim, and Vifor; and participated on data safety monitoring boards for Else Kröner-Fresenius-Stiftung. LSM is stock holder of Bayer and Fresenius Medical Care. MCB received consulting fees from Medtronic and Boston Scientific; speaker honoraria from Medtronic, Boston Scientific, and St Jude Medical; travel expenses from Medtronic, Jonhson & Johnson, Boston Scientific, and St Jude Medical; and participated on advisory boards for Medtronic. CL is member of the Expert Panel for medical devices for the European Commission. CU received consulting fees and speaker honoraria from Medtronic. JRE received consulting fees and speaker honoraria from Medtronic, Abbott, and Boston Scientific. UM received grants from German Centre for Cardiovascular Research (DZHK). All other authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Sham-controlled trials demonstrated safety and efficacy of renal denervation (RDN) to lower blood pressure (BP). Association of baseline heart rate with BP reduction after RDN is incompletely understood., Objectives: The purpose of this analysis was to evaluate the impact of baseline heart rate on BP reduction without antihypertensive medications in the SPYRAL HTN-OFF MED (Global Clinical Study of Renal Denervation With the Symplicity Spyral Multi-electrode Renal Denervation System in Patients With Uncontrolled Hypertension in the Absence of Antihypertensive Medications) Pivotal trial., Methods: Patients removed from any antihypertensive medications were enrolled with office systolic blood pressure (SBP) ≥150 and <180 mm Hg and randomized 1:1 to RDN or sham control. Patients were separated according to baseline office heart rate <70 or ≥70 beats/min. BP changes from baseline to 3 months between treatment arms were adjusted for baseline SBP using analysis of covariance., Results: Scatter plots of 3-month changes in 24-hour and office SBP illustrate a wide range of changes in SBP for different baseline heart rates. Treatment difference at 3 months between RDN and sham control with baseline office heart rate ≥70 beats/min for 24-hour SBP was -6.2 mm Hg (95% CI: -9.0 to -3.5 mm Hg) (P < 0.001) and for baseline office heart rate <70 beats/min it was -0.1 mm Hg (-3.8 to 3.6 mm Hg) (P = 0.97) with an interaction P value of 0.008. Results were similar for changes in office, daytime, and nighttime SBP at 3 months, with a greater reduction in SBP with baseline office heart rate ≥70 beats/min., Conclusions: Reduction in mean office, 24-hour, daytime, and nighttime SBP for RDN at 3 months was greater with baseline office heart rate ≥70 than <70 beats/min, suggesting an association between baseline heart rate and BP reduction after RDN. (SPYRAL PIVOTAL-SPYRAL HTN-OFF MED Study; NCT02439749)., Competing Interests: Funding Support and Author Disclosures The trial is sponsored by Medtronic and was designed in collaboration with the U.S. Food and Drug Administration by the steering committee and sponsor. Profs Böhm, Ukena, Ewen, and Mahfoud are supported by the Deutsche Forschungsgemeinschaft (SFB TTR219, S-01, M-03, M-05). Prof. Böhm has received consulting fees from Abbott Vascular, Bayer AG, Amgen, AstraZeneca, Servier, Medtronic, Vifor, and Boehringer Ingelheim. Dr Tsioufis has received honoraria for advisory boards and lectures from Medtronic, Servier, Bayer, Menarini, Novartis, AstraZeneca, Boehringer Ingelheim, Pfizer, Pythagoras, Sanofi, and Amgen. Dr Kandzari has received institutional research/grant support from Medtronic CardioVascular and Ablative Solutions; and has received personal consulting honoraria from Medtronic CardioVascular. Prof. Kario has received scientific support and speaker honoraria from Daiichi-Sankyo, Sanwa Chemical, Boehringer Ingelheim, Omron Healthcare, A & D Inc, Fukudadenshi Inc, Medtronic, and ReCor Medical. Prof. Weber has received consulting fees from Medtronic, ReCor, and Ablative Solutions. Prof. Schmieder has received consultant fees from Medtronic and ReCor; and has received grant support from Medtronic, ReCor, and Ablative Solutions. Prof. Townsend has received consultant fees from Medtronic, Axio, and Regeneron. Dr Pocock has received consultant fees from Medtronic. Prof. Weil has received honoraria from Medtronic, Novartis, ReCor, Cardinal Health, Bayer, and AstraZeneca. Mr Fahy is an employee of and shareholder for Medtronic. Prof. Mahfoud is supported by Deutsche Gesellschaft für Kardiologie; and has received scientific support and speaker honoraria from Bayer, Boehringer Ingelheim, Medtronic, and ReCor Medical. 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.)

Background Atrial fibrillation (AF) is a major risk factor for mortality. The prevalence, clinical correlates, and prognostic impact of AF in Takotsubo syndrome (TTS) have not yet been investigated in a large patient cohort. This study aimed to investigate the prevalence, clinical correlates, and prognostic impact of AF in patients with TTS. Methods and Results Patients with TTS were enrolled from the International Takotsubo Registry, which is a multinational network with 26 participating centers in Europe and the United States. Patients were dichotomized according to the presence or absence of AF at the time of admission. Of 1584 patients with TTS, 112 (7.1%) had AF. The mean age was higher ( P <0.001), and there were fewer women ( P =0.046) in the AF than in the non-AF group. Left ventricular ejection fraction was significantly lower ( P =0.001), and cardiogenic shock was more often observed ( P <0.001) in the AF group. Both in-hospital ( P <0.001) and long-term mortality ( P <0.001) were higher in the AF group. Multivariable Cox regression analysis revealed that AF was independently associated with higher long-term mortality (hazard ratio, 2.31; 95% CI, 1.50-3.55; P <0.001). Among patients with AF on admission, 42% had no known history of AF before the acute TTS event, and such patients had comparable in-hospital and long-term outcomes compared with those with a history of AF. Conclusions In patients presenting with TTS, AF on admission is significantly associated with increased in-hospital and long-term mortality rates. Whether antiarrhythmics and/or cardioversion are beneficial in TTS with AF should thus be tested in a future trial. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01947621.