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Background: Lung transplantation (LTx) remains the only efficient treatment for selected patients with end-stage pulmonary disease. The age limit for the acceptance of donor organs in LTx is still a matter of debate. We here analyze the impact of donor organ age and the underlying pulmonary disease on short- and long-term outcome and survival after LTx., Methods: Donor and recipient characteristics of LTx recipients at our institution between 03/2003 and 12/2021 were analyzed. Statistical analysis was performed using SPSS and GraphPad software., Results: In 230 patients analyzed, donor age ≥ 55 years was associated with a higher incidence of severe primary graft dysfunction (PGD2/3) (46% vs. 31%, p = 0.03) and reduced long-term survival after LTx (1-, 5- and 10-year survival: 75%, 54%, 37% vs. 84%, 76%, 69%, p = 0.006). Notably, this was only significant in recipients with idiopathic pulmonary fibrosis (IPF) (PGD: 65%, vs. 37%, p = 0.016; 1-, 5-, and 10-year survival: 62%, 38%, 16% vs. 80%, 76%, 70%, p = 0.0002 respectively). In patients with chronic obstructive pulmonary disease (COPD), donor age had no impact on the incidence of PGD2/3 or survival (21% vs. 27%, p = 0.60 and 68% vs. 72%; p = 0.90 respectively). Moreover, we found higher Torque-teno virus (TTV)-DNA levels after LTx in patients with IPF compared to COPD (X 2  = 4.57, p = 0.033). Donor age ≥ 55 is an independent risk factor for reduced survival in the whole cohort and patients with IPF specifically., Conclusions: In recipients with IPF, donor organ age ≥ 55 years was associated with a higher incidence of PGD2/3 and reduced survival after LTx. The underlying pulmonary disease may thus be a relevant factor for postoperative graft function and survival., Trial Registration Number Dkrs: DRKS00033312., (© 2024. The Author(s).)

Implants and medical devices are efficient and practical therapeutic solutions for a multitude of pathologies. Titanium and titanium alloys are used in orthopedics, dentistry, and cardiology. Despite very good mechanical properties and corrosion resistance, titanium implants can fail due to inflammatory or tissue degradation-related complications. Macrophages are major immune cells that control acceptance of failure of the implant. In this study, for the first time, we have performed a systematic analysis of the response of differentially activated human macrophages, M(Control), M(IFNγ), and M(IL-4), to the polished and porous titanium surfaces in order to identify the detrimental effect of titanium leading to the tissue destruction and chronic inflammation. Transcriptome analysis revealed that the highest number of differences between titanium and control settings are found in M(IL-4) that model healing type of macrophages. Real-time quantitative polymerase chain reaction analysis confirmed that both polished and porous titanium affected expression of cytokines, chitinases/chitinase-like proteins, and matrix metalloproteinases (MMPs). Titanium-induced release and activation of MMP7 by macrophages was enhanced by fibroblasts in both juxtacrine and paracrine cell interaction models. Production of titanium-induced MMPs and cytokines associated with chronic inflammation was independent of the presence of Staphylococcus aureus. MMP7, one of the most pronounced tissue-destroying factors, and chitinase-like protein YKL-40 were expressed in CD68+ macrophages in peri-implant tissues of patients with orthopedic implants. In summary, we demonstrated that titanium induces proinflammatory and tissue-destructing responses mainly in healing macrophages, and the detrimental effects of titanium surfaces on implant-adjacent macrophages are independent on the bacterial contamination., Competing Interests: Conflict of interest statement. The authors declare that the research was conducted in the absence of any commercial or financial relationship that could be construed as potential conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for Leukocyte Biology.)

Background: Biomarkers simplifying the diagnostic workup by discriminating between non-ST-segment-elevation myocardial infarction (NSTEMI) and infarct-like myocarditis are an unmet clinical need., Methods and Results: A total of 105 subjects were categorized into groups as follows: ST-segment-elevation myocardial infarction (n=36), NSTEMI (n=22), infarct-like myocarditis (n=19), cardiomyopathy-like myocarditis (n=18), and healthy control (n=10). All subjects underwent cardiac magnetic resonance imaging, and serum concentrations of matrix metalloproteinase-1 (MMP-1) and procollagen type I carboxy terminal propeptide (PICP) were measured. Biomarker concentrations in subjects presenting with acute coronary syndrome and non-ST-segment-elevation, for example NSTEMI or infarct-like myocarditis, categorized as the non-ST-segment-elevation acute coronary syndrome-like cohort, were of particular interest for this study. Compared with healthy controls, subjects with myocarditis had higher serum concentrations of MMP-1 and PICP, while no difference was observed in individuals with myocardial infarction. In the non-ST-segment-elevation acute coronary syndrome-like cohort, MMP-1 concentrations discriminated infarct-like myocarditis and NSTEMI with an area under the receiver operating characteristic curve (AUC) of 0.95 (95% CI, 0.89-1.00), whereas high-sensitivity cardiac troponin T performed inferiorly (AUC, 0.74 [95% CI, 0.58-0.90]; P =0.012). Application of an optimal MMP-1 cutoff had 94.4% sensitivity (95% CI, 72.7%-99.9%) and 90.9% specificity (95% CI, 70.8%-98.9%) for the diagnosis of infarct-like myocarditis in this cohort. The AUC of PICP in this context was 0.82 (95% CI, 0.68-0.97). As assessed by likelihood ratio tests, incorporating MMP-1 or PICP with age and C-reactive protein into composite prediction models enhanced their diagnostic performance., Conclusions: MMP-1 and PICP could potentially be useful biomarkers for differentiating between NSTEMI and infarct-like myocarditis in individuals with non-ST-segment-elevation acute coronary syndrome-like presentation, though further research is needed to validate their clinical applicability.

Background: In the hospital setting, frailty is a significant risk factor, but difficult to measure in clinical practice. We propose a reweighting of an existing diagnoses-based frailty score using routine data from a tertiary care teaching hospital in southern Germany., Methods: The dataset includes patient characteristics such as sex, age, primary and secondary diagnoses and in-hospital mortality. Based on this information, we recalculate the existing Hospital Frailty Risk Score. The cohort includes patients aged ≥ 75 and was divided into a development cohort (admission year 2011 to 2013, N = 30,525) and a validation cohort (2014, N = 11,202). A limited external validation is also conducted in a second validation cohort containing inpatient cases aged ≥ 75 in 2022 throughout Germany (N = 491,251). In the development cohort, LASSO regression analysis was used to select the most relevant variables and to generate a reweighted Frailty Score for the German setting. Discrimination is assessed using the area under the receiver operating characteristic curve (AUC). Visualization of calibration curves and decision curve analysis were carried out. Applicability of the reweighted Frailty Score in a non-elderly population was assessed using logistic regression models., Results: Reweighting of the Frailty Score included only 53 out of the 109 frailty-related diagnoses and resulted in substantially better discrimination than the initial weighting of the score (AUC = 0.89 vs. AUC = 0.80, p < 0.001 in the validation cohort). Calibration curves show a good agreement between score-based predictions and actual observed mortality. Additional external validation using inpatient cases aged ≥ 75 in 2022 throughout Germany (N = 491,251) confirms the results regarding discrimination and calibration and underlines the geographic and temporal validity of the reweighted Frailty Score. Decision curve analysis indicates that the clinical usefulness of the reweighted score as a general decision support tool is superior to the initial version of the score. Assessment of the applicability of the reweighted Frailty Score in a non-elderly population (N = 198,819) shows that discrimination is superior to the initial version of the score (AUC = 0.92 vs. AUC = 0.87, p < 0.001). In addition, we observe a fairly age-stable influence of the reweighted Frailty Score on in-hospital mortality, which does not differ substantially for women and men., Conclusions: Our data indicate that the reweighted Frailty Score is superior to the original Frailty Score for identification of older, frail patients at risk for in-hospital mortality. Hence, we recommend using the reweighted Frailty Score in the German in-hospital setting., (© 2024. The Author(s).)

Objective: This study examines outcome and durability of physician made bovine pericardial tube grafts in aortic infections in all anatomical locations., Methods: This was a retrospective and prospective international multicentre study. Peri-operative and long term outcomes of patients undergoing in situ aortic reconstruction for native or graft infections with physician made bovine pericardial tube grafts between January 2008 and December 2020 in four European tertiary referral centres were analysed. The primary endpoint was recurrent aortic infection. Secondary endpoints were persistent infection, aortic re-operation for infection, graft related complications, and death., Results: One hundred and sixty eight patients (77% male, mean age 67 ± 11 years) were identified: 38 (23%) with native and 130 (77%) with aortic graft infection. The thirty day mortality rate was 15% (n = 26) overall, 11% (n = 4), and 17% (n = 22) for native and aortic graft infections, respectively (p = .45). Median follow up was 26 months (interquartile range [IQR] 10, 51). Estimated survival at one, two, three, and five years was 64%, 60%, 57%, and 50%, and significantly better for native (81%, 77%, 77%, and 69%) than for graft infections (58%, 55%, 51%, and 44%; p = .011). Nine patients (5.3%) had persistent infection and 10 patients (6%) had aortic re-infection after a median of 10 months (IQR 5, 22), resulting in an estimated freedom from re-infection at one, two, three, and five years of 94%, 92%, 90%, and 86%. Estimated freedom from graft complications at one, two, three, and five years was 91%, 89%, 87%, and 87%., Conclusion: This multicentre study demonstrates low re-infection rates when using physician made bovine pericardial tube grafts, comparable to those of other biological grafts. The rate of graft complications, mainly anastomotic aneurysms and stenoses, was low, while graft degeneration was absent. Physician made bovine pericardial tube grafts are an excellent tool for in situ reconstruction in the setting of native aortic infection or aortic graft infection., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: There are different definitions of periprocedural myocardial infarction (PPMI) both in terms of thresholds for cardiac biomarkers and the ancillary criteria for myocardial ischemia. Cardiac Troponin I (cTnI) and cardiac Troponin T (cTnT) are used interchangeably to diagnose PPMI., Objectives: This study evaluated the frequency of periprocedural myocardial injury and infarction as defined by the Society of Cardiovascular Angiography & Interventions (SCAI), the Academic Research Consortium-2 (ARC-2), and the 4th Universal definition of MI (4UDMI) stratified using cTnT versus cTnI, among patients with chronic coronary syndrome (CCS) and unstable angina., Results: Among 830 patients, PPMI rates according to the SCAI, ARC2 and 4UDMI criteria were 4.34 %, 2.05 %, and 4.94 % respectively, with higher rates seen for all definitions when using cTnI versus cTnT (SCAI: 9.84 % vs. 1.91 %, p < 0.001; ARC 2: 3.15 % vs. 1.56 %, p = 0.136; and 4UDMI 5.91 % vs. 4.51 %, p = 0.391). Minor and major periprocedural myocardial injury was respectively observed in 58.31 % and 27.10 % of patients, with rates of both significantly higher when using cTnI versus cTnT (Minor: 69.29 % vs. 53.47 %, p < 0.001, Major: 49.21 % vs. 17.36 %, p < 0.001)., Conclusions: Among patients with CCS and unstable angina, PPMIs defined by SCAI occurred more frequently when using cTnI as opposed to cTnT, whereas the type of troponin had no impact on the incidence of PPMIs according to the ARC-2 and 4UDMI., Competing Interests: Declaration of competing interest Dr. Ninomiya reports a grant from Abbott Medical Japan outside the submitted work. Dr. Kotoku has received a grant for studying overseas from Fukuda Foundation for Medical Technology. Dr. Serruys reports institutional grants from Sinomedical Sciences Technology, SMT (Sahajanand Medical technologies), Meril Life sciences, Philips/Volcano, Xeltis, and HeartFlow, outside the submitted work. Dr. Onuma reports institutional grants from Sinomedical Sciences Technology, SMT (Sahajanand Medical technologies), Meril Life sciences, Philips/Volcano, Xeltis, and HeartFlow, outside the submitted work. Dr. Sabate is a consultant for Abbott vascular and iVascular outside the submitted work. Dr. Mollmann is a consultant for Abbott vascular, Boston Scientific, Medtronic and SMT outside the submitted work., (Copyright © 2024. Published by Elsevier Inc.)

Objectives: The aim of this study was to report on mid-term outcomes after endovascular aortic repair (EVAR) in patients with Marfan (MFS) or Loeys-Dietz (LDS) syndrome., Methods: We analysed data from 2 European centres of patients with MFS and LDS undergoing EVAR. Patients were analysed based on (i) timing of the procedure (planned versus emergency procedure) and (ii) the nature of the landing zone (safe versus non-safe). The primary end-point was freedom from reintervention. Secondary end-points were freedom from stroke, bleeding and death., Results: A population of 419 patients with MFS (n = 352) or LDS (n = 67) was analysed for the purpose of this study. Thirty-nine patients (9%) underwent EVAR. Indications for thoracic endovascular aortic repair or EVAR were aortic dissection in 13 (33%) patients, aortic aneurysm in 22 (57%) patients and others (intercostal patch aneurysm, penetrating atherosclerotic ulcer, pseudoaneurysm, kinking of frozen elephant trunk (FET)) in 4 (10%) patients. Thoracic endovascular repair was performed in 34 patients, and abdominal endovascular aortic repair was performed in 5 patients. Mean age at 1st thoracic endovascular aortic repair/EVAR was 48.5 ± 15.4 years. Mean follow-up after 1st thoracic endovascular aortic repair/EVAR was 5.9 ± 4.4 years. There was no statistically significant difference in the rate of reinterventions between patients with non-safe landing zone and the patients with safe proximal landing zone (P = 0.609). Furthermore, there was no increased probability for reintervention after planned endovascular intervention compared to emergency procedures (P = 0.916). Mean time to reintervention, either open surgical or endovascular, after planned endovascular intervention was in median 3.9 years (95% confidence interval 2.0-5.9 years) and 2.0 years (95% confidence interval -1.1 to 5.1 years) (P = 0.23) after emergency procedures., Conclusions: EVAR in patients with MFS and LDS and a safe landing zone is feasible and safe. Endovascular treatment is a viable option when employed by a multi-disciplinary aortic team even if the landing zone is in native tissue., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

This analysis aimed to evaluate the effect of 1- versus 3-month dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) in older patients. Data from 3 prospective, single-arm studies (XIENCE Short DAPT Program), including patients with high bleeding risk successfully treated with an everolimus-eluting stent (XIENCE, Abbott) were analyzed. DAPT was discontinued at 1 or at 3 months in patients free from ischemic events and adherent to DAPT. Patients were stratified according to age (≥75 and <75 years). The primary end point was all-cause death or myocardial infarction (MI). The key secondary end point was Bleeding Academic Research Consortium type 2 to 5 bleeding. The outcomes were assessed from 1 to 12 months after index PCI. Of 3,364 patients, 2,241 (66.6%) were aged ≥75 years. The risk of death or MI was similar with 1- versus 3-month DAPT in patients aged ≥75 (8.5% vs 8.0%, adjusted hazard ratio [HR] 0.95, 95% confidence interval [CI] 0.69 to 1.30) and <75 years (6.9% vs 7.8%, adjusted HR 0.97, 95% CI 0.60 to 1.57, interaction p = 0.478). Bleeding Academic Research Consortium type 2 to 5 bleeding was consistently lower with 1- than with 3-month DAPT in patients aged ≥75 years (7.2% vs 9.4%, adjusted HR 0.66, 95% CI 0.48 to 0.91) and <75 years (9.7% vs 11.9%, adjusted HR 0.86, 95% CI 0.57 to 1.29, interaction p = 0.737). In conclusion, in patients at high bleeding risk who underwent PCI, patients older and younger than 75 years derived a consistent benefit from 1- compared with 3-month DAPT in terms of bleeding reduction, with no increase in all-cause death or MI at 1 year., Competing Interests: Declaration of competing interest Dr. Spirito received a research grant for the Swiss National Science Foundation. Dr. Angiolillo declares that he has received consulting fees or honoraria from Abbott, Amgen, AstraZeneca, Bayer, Biosensors, Boehringer Ingelheim, Bristol-Myers Squibb, Chiesi, CSL Behring, Daiichi Sankyo, Eli Lilly, Haemonetics, Janssen, Merck, Novartis, PhaseBio, PLx Pharma, Pfizer, Sanofi and Ventura, outside the present work. D.J.A. also declares that his institution has received research grants from Amgen, AstraZeneca, Bayer, Biosensors, CeloNova, CSL Behring, Daiichi Sankyo, Eisai, Eli Lilly, Gilead, Janssen, Matsutani Chemical Industry Co., Merck, Novartis, Osprey Medical, Renal Guard Solutions and Scott R. MacKenzie Foundation. Dr Bangalore received consulting fees or been on the advisory board for Abbott Vascular, Boston Scientific, Biotronik, Amgen, Pfizer,Merck, Viatris, and REATA. Dr. Vranckx received personal fees from Daichii Sankyo, Bayer AG, Pfizer-Bristol Meyers Squibb alliance, Novartis, CSL Behring not related to this research. Dr. Bhatt discloses the following relationships - Advisory Board: Angiowave, Bayer, Boehringer Ingelheim, Cardax, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, High Enroll, Janssen, Level Ex, McKinsey, Medscape Cardiology, Merck, MyoKardia, NirvaMed, Novo Nordisk, PhaseBio, PLx Pharma, Regado Biosciences, Stasys; Board of Directors: Angiowave (stock options), Boston VA Research Institute, Bristol-Myers Squibb (stock), DRS.LINQ (stock options), High Enroll (stock), Society of Cardiovascular Patient Care, TobeSoft; Chair: Inaugural Chair, American Heart Association Quality Oversight Committee; Consultant: Broadview Ventures, Hims; Data Monitoring Committees: Acesion Pharma, Assistance Publique-Hôpitaux de Paris, Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), Boston Scientific (Chair, PEITHO trial), Cleveland Clinic (including for the ExCEED trial, funded by Edwards), Contego Medical (Chair, PERFORMANCE 2), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi Sankyo; for the ABILITY-DM trial, funded by Concept Medical), Novartis, Population Health Research Institute; Rutgers University (for the NIH-funded MINT Trial); Honoraria: American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org; Chair, ACC Accreditation Oversight Committee), Arnold and Porter law firm (work related to Sanofi/Bristol-Myers Squibb clopidogrel litigation), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim; AEGIS-II executive committee funded by CSL Behring), Belvoir Publications (Editor in Chief, Harvard Heart Letter), Canadian Medical and Surgical Knowledge Translation Research Group (clinical trial steering committees), CSL Behring (AHA lecture), Cowen and Company, Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial, funded by Ferring Pharmaceuticals), HMP Global (Editor in Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest Editor; Associate Editor), K2P (Co-Chair, interdisciplinary curriculum), Level Ex, Medtelligence/ReachMD (CME steering committees), MJH Life Sciences, Oakstone CME (Course Director, Comprehensive Review of Interventional Cardiology), Piper Sandler, Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and USA national co-leader, funded by Bayer), Slack Publications (Chief Medical Editor, Cardiology Today's Intervention), Society of Cardiovascular Patient Care (Secretary/Treasurer), WebMD (CME steering committees), Wiley (steering committee); Other: Clinical Cardiology (Deputy Editor), NCDR-ACTION Registry Steering Committee (Chair), VA CART Research and Publications Committee (Chair); Patent: Sotagliflozin (named on a patent for sotagliflozin assigned to Brigham and Women's Hospital who assigned to Lexicon; neither I nor Brigham and Women's Hospital receive any income from this patent); Research Funding: Abbott, Acesion Pharma, Afimmune, Aker Biomarine, Alnylam, Amarin, Amgen, AstraZeneca, Bayer, Beren, Boehringer Ingelheim, Boston Scientific, Bristol-Myers Squibb, Cardax, CellProthera, Cereno Scientific, Chiesi, CinCor, Cleerly, CSL Behring, Eisai, Ethicon, Faraday Pharmaceuticals, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Garmin, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Janssen, Javelin, Lexicon, Lilly, Medtronic, Merck, Moderna, MyoKardia, NirvaMed, Novartis, Novo Nordisk, Otsuka, Owkin, Pfizer, PhaseBio, PLx Pharma, Recardio, Regeneron, Reid Hoffman Foundation, Roche, Sanofi, Stasys, Synaptic, The Medicines Company, Youngene, 89Bio; Royalties: Elsevier (Editor, Braunwald's Heart Disease); Site Co-Investigator: Abbott, Biotronik, Boston Scientific, CSI, Endotronix, St. Jude Medical (now Abbott), Philips, SpectraWAVE, Svelte, Vascular Solutions; Trustee: American College of Cardiology; Unfunded Research: FlowCo, Takeda. Dr Campo received institutional research grants from SMT, Siemens, GE Healthcare, GADA and Abbott Vascular outside the present work. Dr. Neumann received grants or fees from Amgen, Bayer Health Care, Biotronik, Boehringer Ingelheim, Boston Scientific, Daiichi Sankyo, Edwards Lifesciences, Ferrer, Pfizer, Novartis, GlaxoSmithKline, Abbott Vascular, and Medtronic. Dr. Toelg received speaker honoraria from Boston Scientific, Abbott Vascular, and Biotronik. Dr. Valgimigli reports personal fees from Astra Zeneca, grants and personal fees from Terumo, personal fees from Alvimedica/CID, personal fees from Abbott Vascular, personal fees from Daiichi Sankyo, personal fees from Opsens, personal fees from Bayer, personal fees from CoreFLOW, personal fees from IDORSIA PHARMACEUTICALS LTD, personal fees from Universität Basel | Dept. Klinische Forschung, personal fees from Vifor, personal fees from Bristol-Myers Squib SA, personal fees from iVascular, personal fees from Medscape, outside the submitted work. Dr. Varenne received lectures fees by AV and Biotronik. Dr. Windecker reports research, travel or educational grants to the institution without personal remuneration from Abbott, Abiomed, Amgen, Astra Zeneca, Bayer, Braun, Biotronik, Boehringer Ingelheim, Boston Scientific, Bristol-Myers Squibb, Cardinal Health, CardioValve, Cordis Medical, Corflow Therapeutics, CSL Behring, Daiichi Sankyo, Edwards Lifesciences, Farapulse Inc. Fumedica, Guerbet, Idorsia, Inari Medical, InfraRedx, Janssen-Cilag, Johnson & Johnson, Medalliance, Medicure, Medtronic, Merck Sharp & Dohm, Miracor Medical, Novartis, Novo Nordisk, Organon, OrPha Suisse, Pharming Tech. Pfizer, Polares, Regeneron, Sanofi-Aventis, Servier, Sinomed, Terumo, Vifor, V-Wave. Dr Windecker served as advisory board member and/or member of the steering/executive group of trials funded by Abbott, Abiomed, Amgen, Astra Zeneca, Bayer, Boston Scientific, Biotronik, Bristol-Myers Squibb, Edwards Lifesciences, MedAlliance, Medtronic, Novartis, Polares, Recardio, Sinomed, Terumo, and V-Wave with payments to the institution but no personal payments. He is also member of the steering/executive committee group of several investigator-initiated trials that receive funding by industry without impact on his personal remuneration. Dr. Mehran reports institutional research payments from Abbott, Abiomed, Alleviant Medical, Amgen, AM-Pharma, Arena, AstraZeneca, Atricure, Bayer, Biosensors, Biotronik, Boston Scientific, Bristol-Myers Squibb, CardiaWave, CeloNova, Chiesi, Concept Medical, CSL Behring, Cytosorbents, Daiichi Sankyo, Element Science, Faraday, Humacyte, Idorsia Pharmaceuticals, Janssen, Medtronic, Novartis, OrbusNeich, PhaseBio, Philips, Pi-Cardia, PLx Pharma, RenalPro, RM Global, Shockwave, Vivasure, Zoll; personal fees from Cine-Med Research, Novartis, WebMD; equity <1% in Applied Therapeutics, Elixir Medical, Stel, ControlRad (spouse); scientific advisory board for AMA, ACC (BOT Member), SCAI (Women in Innovations Committee Member), JAMA associate editor; faculty CRF (no fee). The remaining authors have no competing interest to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Aims: Myocardial infarction (MI) is a major cause of death worldwide. Effective treatments are required to improve recovery of cardiac function following MI, with the aim of improving patient outcomes and preventing progression to heart failure. The perfused but hypocontractile region bordering an infarct is functionally distinct from the remote surviving myocardium and is a determinant of adverse remodelling and cardiac contractility. Expression of the transcription factor RUNX1 is increased in the border zone 1-day after MI, suggesting potential for targeted therapeutic intervention., Objective: This study sought to investigate whether an increase in RUNX1 in the border zone can be therapeutically targeted to preserve contractility following MI., Methods and Results: In this work we demonstrate that Runx1 drives reductions in cardiomyocyte contractility, calcium handling, mitochondrial density, and expression of genes important for oxidative phosphorylation. Both tamoxifen-inducible Runx1-deficient and essential co-factor common β subunit (Cbfβ)-deficient cardiomyocyte-specific mouse models demonstrated that antagonizing RUNX1 function preserves the expression of genes important for oxidative phosphorylation following MI. Antagonizing RUNX1 expression via short-hairpin RNA interference preserved contractile function following MI. Equivalent effects were obtained with a small molecule inhibitor (Ro5-3335) that reduces RUNX1 function by blocking its interaction with CBFβ., Conclusions: Our results confirm the translational potential of RUNX1 as a novel therapeutic target in MI, with wider opportunities for use across a range of cardiac diseases where RUNX1 drives adverse cardiac remodelling., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background and Objectives : Patients with chronic total occlusions of the coronary arteries are either treated with PCI or referred for surgical revascularization. We analyzed the patients with chronic occluded coronary arteries that were surgically treated and aimed to describe the anatomical characteristics, revascularization rates, and in-hospital outcomes achieved with coronary artery bypass grafting. Methods : Angiographic data of 2005 patients with coronary artery disease treated in our institution between January 2005 and December 2014 were retrospectively analyzed. A total of 1111 patients with at least one coronary total occlusion were identified. We reviewed the preoperative coronary angiograms and surgical protocols to determine the presence, localization, and revascularization of coronary occlusions. We also evaluated the perioperative data and in-hospital outcomes. Results : The median age of the study population was 68 years (25th-75th percentiles, 61.0-74.0). Three-vessel disease was present in 94.8% of patients and the rest (5.8%) had a two-vessel disease. The localizations of the occlusions were as follows: 68.4% in the RCA system, 26.4% in the LAD, and 28.5% in the LCX system. Multiple occlusions were present in 22.6% of the patients. Complete coronary total occlusion revascularization was achieved in 86.1% of the patients. The overall in-hospital mortality was 2.3%. The median in-hospital stay was 14.0 days. After logistic regression analysis, age (odds ratio 3.44 [95% confidence interval, 1.81-6.53], p < 0.001, for a 10-year increase) and the presence of peripheral artery disease (odds ratio 3.32 [1.39-7.93], p = 0.007) were the only statistically significant independent predictors of in-hospital mortality. Conclusions : A high revascularization rate and favorable in-hospital outcomes are achieved with coronary artery bypass surgery in patients with multi-vessel diseases and coronary total occlusions. Older age and the presence of peripheral artery disease are independent predictors of in-hospital mortality. A long-term follow-up and the type of graft (arterial vs. venous) used would bring more useful data for this type of revascularization.

Background: The optimal duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) in patients on long-term oral anticoagulation (OAC) therapy is still uncertain., Objectives: The aim of this analysis was to assess the effects of 1- vs 3-month DAPT in patients with and those without concomitant OAC included in the XIENCE Short DAPT program., Methods: The XIENCE Short DAPT program enrolled patients with high bleeding risk who underwent successful PCI with a cobalt-chromium everolimus-eluting stent. DAPT was discontinued at 1 or 3 months in patients free from ischemic events and adherent to treatment. The effect of 1- vs 3-month DAPT was compared in patients with and those without OAC using propensity score stratification. The primary endpoint was all-cause death or any myocardial infarction (MI). The key secondary endpoint was Bleeding Academic Research Consortium (BARC) types 2 to 5 bleeding. Outcomes were assessed from 1 to 12 months after index PCI., Results: Among 3,364 event-free patients, 1,462 (43%) were on OAC. Among OAC patients, the risk for death or MI was similar between 1- and 3-month DAPT (7.4% vs 8.8%; adjusted HR: 0.74; 95% CI: 0.49-1.11; P = 0.139), whereas BARC types 2 to 5 bleeding was lower with 1-month DAPT (adjusted HR: 0.71; 95% CI: 0.51-0.99; P = 0.046). These effects were consistent in patients with and those without OAC (P for interaction = NS)., Conclusions: Between 1 and 12 months after PCI, 1-month compared with 3-month DAPT was associated with similar rates of all-cause death or MI and a reduced rate of BARC types 2 to 5 bleeding, irrespective of OAC treatment., Competing Interests: Funding Support and Author Disclosures The study was sponsored by Abbott. Dr Valgimigli has received personal fees from AstraZeneca, Alvimedica/CID, Abbott Vascular, Daiichi Sankyo, Opsens, Bayer, CoreFlow, Idorsia Pharmaceuticals, Universität Basel | Departement Klinische Forschung, Vifor, Bristol Myers Squibb, iVascular, and Medscape; and has received grants and personal fees from Terumo, outside the submitted work. Dr Spirito has received a research grant from the Swiss National Science Foundation. Dr Angiolillo has received consulting fees or honoraria from Abbott, Amgen, AstraZeneca, Bayer, Biosensors, Boehringer Ingelheim, Bristol Myers Squibb, Chiesi, Daiichi Sankyo, Eli Lilly, Haemonetics, Janssen, Merck, Novartis, PhaseBio, PLx Pharma, Pfizer, Sanofi, and Ventura, outside the submitted work; and has received research grants to his institution from Amgen, AstraZeneca, Bayer, Biosensors, CeloNova, CSL Behring, Daiichi Sankyo, Eisai, Eli Lilly, Gilead, Janssen, Matsutani Chemical Industry, Merck, Novartis, Osprey Medical, Renal Guard Solutions, and the Scott R. MacKenzie Foundation. Dr Bangalore has received consulting fees or has been an advisory board member for Abbott Vascular, Boston Scientific, Biotronik, Amgen, Pfizer, Merck, Viatris, and REATA. Dr Vranckx has received personal fees from Daiichi Sankyo, Bayer, Pfizer/Bristol Myers Squibb, Novartis, and CSL Behring, not related to this research. Dr Bhatt has served on advisory boards for AngioWave, Bayer, Boehringer Ingelheim, Cardax, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, High Enroll, Janssen, Level Ex, McKinsey, Medscape Cardiology, Merck, MyoKardia, NirvaMed, Novo Nordisk, PhaseBio, PLx Pharma, Regado Biosciences, and Stasys; has served on boards of directors for AngioWave, the Boston VA Research Institute, Bristol Myers Squibb, DRS.LINQ, High Enroll, the Society of Cardiovascular Patient Care, and TobeSoft; has stock or stock options with AngioWave, Bristol Myers Squibb, and DRS.LINQ; has served as inaugural chair of the American Heart Association Quality Oversight Committee; has been a consultant for Broadview Ventures; has served on data monitoring committees for Acesion Pharma, Assistance Publique–Hôpitaux de Paris, the Baim Institute for Clinical Research (formerly the Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), Boston Scientific (chair, PEITHO trial), the Cleveland Clinic (including for the ExCEED trial, funded by Edwards Lifesciences), Contego Medical (chair, PERFORMANCE 2 trial), the Duke Clinical Research Institute, the Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi Sankyo, and for the ABILITY-DM trial, funded by Concept Medical), Novartis, the Population Health Research Institute, and Rutgers University (for the National Institutes of Health–funded MINT trial); has received honoraria from the American College of Cardiology (senior associate editor, Clinical Trials and News, ACC.org, and chair of the American College of Cardiology Accreditation Oversight Committee), the law firm of Arnold and Porter (work related to Sanofi/Bristol Myers Squibb clopidogrel litigation), the Baim Institute for Clinical Research (formerly the Harvard Clinical Research Institute; RE-DUAL PCI clinical trial steering committee, funded by Boehringer Ingelheim; AEGIS-II executive committee, funded by CSL Boehringer), Belvoir Publications (editor-in-chief, Harvard Heart Letter), the Canadian Medical and Surgical Knowledge Translation Research Group (clinical trial steering committees), Cowen & Company, the Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial, funded by Ferring Pharmaceuticals), HMP Global (editor-in-chief, Journal of Invasive Cardiology), the Journal of the American College of Cardiology (guest editor, associate editor), K2P (cochair, interdisciplinary curriculum), Level Ex, Medtelligence/ReachMD (continuing medical education steering committees), MJH Life Sciences, Oakstone CME (course director, Comprehensive Review of Interventional Cardiology), Piper Sandler, the Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and U.S. national coleader, funded by Bayer), Slack Publications (chief medical editor, Cardiology Today’s Intervention), the Society of Cardiovascular Patient Care (secretary and treasurer), WebMD (continuing medical education steering committees), and John Wiley (steering committee); has other relationships with Clinical Cardiology (deputy editor), the NCDR-ACTION Registry Steering Committee (chair), and the VA CART Research and Publications Committee (chair); has been named on a patent for sotagliflozin, assigned to Brigham and Women’s Hospital, which assigned to Lexicon (neither Dr Bhatt nor Brigham and Women’s Hospital receives any income from this patent); has received research funding from 89Bio, Abbott, Acesion Pharma, Afimmune, Aker Biomarine, Amarin, Amgen, AstraZeneca, Bayer, Beren, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cardax, CellProthera, Cereno Scientific, Chiesi, CSL Behring, Eisai, Ethicon, Faraday Pharmaceuticals, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Garmin, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Janssen, Javelin, Lexicon, Lilly, Medtronic, Merck, Moderna, Myo-Kardia, NirvaMed, Novartis, Novo Nordisk, Owkin, Pfizer, PhaseBio, PLx Pharma, Recardio, Regeneron, the Reid Hoffman Foundation, Roche, Sanofi, Stasys, Synaptic, The Medicines Company, and Youngene; has received royalties from Elsevier (editor, Cardiovascular Intervention: A Companion to Braunwald’s Heart Disease); has been a site coinvestigator for Abbott, Biotronik, Boston Scientific, CSI, Endotronix, St. Jude Medical (now Abbott), Philips, SpectraWAVE, Svelte, and Vascular Solutions; has been a trustee for the American College of Cardiology; and has performed unfunded research for FlowCo andTakeda. Dr Campo has received institutional research grants outside the submitted work. Dr Neumann has received grants or fees from Amgen, Bayer Health Care, Biotronik, Boehringer Ingelheim, Boston Scientific, Daiichi Sankyo, Edwards Lifesciences, Ferrer, Pfizer, Novartis, GlaxoSmithKline, Abbott Vascular, and Medtronic. Dr Toelg has received speaker honoraria from Boston Scientific, Abbott Vascular, and Biotronik. Dr Windecker has received research, travel, or educational grants to the institution from Abbott, Abiomed, Amgen, AstraZeneca, Bayer, Biotronik, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cardinal Health, CardioValve, Corflow Therapeutics, CSL Behring, Daiichi Sankyo, Edwards Lifesciences, Guerbet, Infraredx, Janssen-Cilag, Johnson & Johnson, Medicure, Medtronic, Merck Sharp & Dohme, Miracor Medical, Novartis, Novo Nordisk, Organon, OrPha Suisse, Pfizer, Polares, Regeneron, Sanofi, Servier, Sinomed, Terumo, Vifor, and V-Wave; serves as an advisory board member and/or a member of the steering or executive groups of trials funded by Abbott, Abiomed, Amgen, AstraZeneca, Bayer, Boston Scientific, Biotronik, Bristol Myers Squibb, Edwards Lifesciences, Janssen, MedAlliance, Medtronic, Novartis, Polares, Recardio, Sinomed, Terumo, V-Wave, and Xeltis, with payments to the institution but no personal payments; and is a member of the steering or executive committee groups of several investigator-initiated trials that receive funding from industry, without impact on his personal remuneration. Dr Mehran has received institutional research payments from Abbott, Abiomed, Alleviant Medical, Amgen, AM-Pharma, Arena, AstraZeneca, Atricure, Bayer, Biosensors, Biotronik, Boston Scientific, Bristol Myers Squibb, CardiaWave, CeloNova, Chiesi, Concept Medical, CSL Behring, Cytosorbents, Daiichi Sankyo, Element Science, Faraday, Humacyte, Idorsia Pharmaceuticals, Janssen, Medtronic, Novartis, OrbusNeich, PhaseBio, Philips, Pi-Cardia, PLx Pharma, RenalPro, RM Global, Shockwave, Vivasure, and Zoll; has received personal fees from Cine-Med Research, Novartis, and WebMD; holds equity (<1%) in Applied Therapeutics, Elixir Medical, Stel, and ControlRad (spouse); is a scientific advisory board member for the American Medical Association, the American College of Cardiology (Board of Trustees member), and the Society for Cardiovascular Angiography and Interventions (Women in Innovations Committee member); is an associate editor for JAMA; and is a faculty member for the Cardiovascular Research Foundation (no fee). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Paravalvular leak (PVL) is a shortcoming that can erode the clinical benefits of transcatheter valve replacement (TAVR) and therefore a readily applicable method (aortography) to quantitate PVL objectively and accurately in the interventional suite is appealing to all operators. The ratio between the areas of the time-density curves in the aorta and left ventricular outflow tract (LVOT-AR) defines the regurgitation fraction (RF). This technique has been validated in a mock circulation; a single injection in diastole was further tested in porcine and ovine models. In the clinical setting, LVOT-AR was compared with trans-thoracic and trans-oesophageal echocardiography and cardiac magnetic resonance imaging. LVOT-AR > 17% discriminates mild from moderate aortic regurgitation on echocardiography and confers a poor prognosis in multiple registries, and justifies balloon post-dilatation. The LVOT-AR differentiates the individual performances of many old and novel devices and is being used in ongoing randomized trials and registries., Competing Interests: PWS reports personal fees from Philips/Volcano, SMT, Novartis, Xeltis, Merillife. PCR has no conflict of interest. Aben is an employee of Pie Medical Imaging. MC is employed by and holds shares of Xeltis BV CS is an employee of Philips Healthcare. MA-W reports other from Medtronic, other from Boston Scientific, outside the submitted work. NP is a consultant to Medtronic, Peijia, and MicroPort. RM is an employee of Boston Scientific. AR reports grants and personal fees from Boston Scientific, personal fees from Edwards Lifesciences, outside the submitted work. KK reports personal fees from Abbott, personal fees from Boston Scientific, personal fees from Edwards Lifesciences, personal fees from Medtronic, personal fees from Meril Life Sciences, outside the submitted work. NVR reports grants and personal fees from Abbott, grants from Philips, grants from Biotronik, and personal fees from Microport, outside the submitted work. Rudolph is a proctor, speaker’s honoraria of JenaValve. FJN reports personal fees from Amgen, personal fees from Boehringer Ingelheim, personal fees from Daiichi Sankyo, grants and personal fees from Pfizer, grants and personal fees from Biotronic, grants and personal fees from Edwards Lifesciences, grants from Medtronic, grants and personal fees from Bayer Healthcare, personal fees from Novartis, grants from GlaxoSmithKline, grants and personal fees from Boston Scientific, personal fees from Ferrer, outside the submitted work. IJA-S is a proctor for Medtronic, Boston Scientific and Meril Life. OS and YO report several institutional research grants, outside the submitted work. 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., (© 2023 Abdelshafy, Serruys, Tsai, Revaiah, Grag, Aben, Schultz, Abdelghani, Tonino, Miyazaki, Rutten, Cox, Sahyoun, Teng, Tateishi, Abdel-Wahab, Piazza, Pighi, Modolo, van Mourik, Wykrzykowska, de Wintet, Lemos, de Brito, Kawashima, Søendergaard, Rosseel, Wang, Gao, Tao, Rück, Kim, van Royen, Terkelsen, Nissen, Adam, Rudolph, Wienemann, Torii, Neuman, Schoechlin, Chen, Elkoumy, Elzomor, Amat-Santos, Mylotte, Soliman and Onuma.)

Objectives: This study aims to describe the outcomes of surgical correction for anomalous aortic origin of coronary artery (AAOCA) with regard to symptom relief., Methods: We performed a retrospective multicentre study including surgical patients who underwent correction for AAOCA between 2009 and 2022. Patients who underwent concomitant cardiac procedures were also included. However, to analyse symptom relief, we only assessed the subgroup of symptomatic patients who underwent isolated correction for AAOCA., Results: A total of 71 consecutive patients (median age 55, range 12-83) who underwent surgical correction for AAOCA were included in the study. Right-AAOCA was present in 56 patients (79%), left-AAOCA in 11 patients (15%) and single coronary ostium AAOCA in 4 patients (6%). Coronary unroofing was performed in 72% of the patients, coronary reimplantation in 28% and an additional neo-ostium patchplasty in 13% of the patients. In 39% of the patients, a concomitant cardiac procedure was performed. During follow-up, no cardiovascular-related death was observed. Three patients (4.2%) had a myocardial infarction and underwent postoperative coronary artery bypass grafting. Six patients (8.5%) needed postoperative temporary mechanical circulatory support. Among the 34 symptomatic patients who underwent isolated AAOCA correction, 70% were completely asymptomatic after surgery, 12% showed symptom improvement and no symptom improvement was observed in 18% of the patients (median follow-up 3.5 years, range 0.3-11.1)., Conclusions: Correction for AAOCA can be safely performed with or without concomitant cardiac procedures. Performing AAOCA correction leads to a significant improvement in symptoms for most patients., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: COVID-19 has caused the deferral of millions of elective procedures, likely resulting in a backlog of cases. We estimate the number of postponed surgical aortic valve replacement (sAVR) and transcatheter aortic valve replacement (TAVR) procedures during the first two waves of the COVID-19 pandemic in Germany., Methods: Using German national records, all isolated TAVR and sAVR procedures between 2007 and 2020 were identified. Using weekly TAVR and sAVR procedures between 2017 and 2019, we created a forecast for 2020 and compared it with the observed number of procedures in 2020., Results: In Germany, a total of 225,398 isolated sAVR and 159,638 isolated TAVR procedures were conducted between 2007 and 2020 that were included in our analysis. The reduction in all AVR procedures (sAVR and TAVR) for the entire year 2020 was 19.07% (95%CI: 15.19-22.95%). During the first wave of the pandemic (week 12-21), the mean weekly reduction was 32.06% (23.44-40.68%) and during the second wave of the pandemic (week 41-52), the mean weekly reduction was 25.58% (14.19-36.97%). The number of sAVR procedures decreased more than the number of TAVR procedures (24.63% vs. 16.42% for the entire year 2020)., Conclusion: The first year of the COVID-19 pandemic saw a substantial postponing of AVR procedures in Germany. Postponing was higher for sAVR than for TAVR procedures and less pronounced during the second wave of the COVID-19 pandemic., (© 2023. The Author(s).)

Background: The storage time of packed red blood cells (pRBC) is an indicator of change in the product's pH, potassium, and lactate levels. Blood-gas analysis is a readily available bedside tool on every intensive care ward to measure these factors prior to application, thus facilitating a calculated decision on a transfusion's quantity and duration.Our first goal is to assess the impact of storage time on pH, potassium, and lactate levels in pRBC. The influence of those parameters in the transfused children will then be evaluated., Methods: In this retrospective study, we conducted blood-gas analyses of pRBC units before they were administered over 4 hours to neonates, infants, and children in our pediatric cardiac intensive care ward. All patients underwent regular blood-gas analyses themselves, before and after transfusion., Results: We observed a highly significant correlation between the storage time of pRBC units and a drop in pH, as well as an increase in potassium and lactate of stored red cells ( p < 0.0001). Median age of recipients with a complete blood-gas dataset was 0.1 (interquartile range [IQR] = 0.0-0.7) years; median pRBC storage duration was 6 (IQR = 5-8) days. Further analyses showed no statistically significant effect on children's blood gases within 4 hours after transfusion, even after stratifying for pRBC storage time ≤7 days and >7 days., Conclusion: Stored red blood cells show a rapid decrease in pH and increase in potassium and lactate. Slow transfusion of these units had no adverse effects on the recipients' pH, potassium, and lactate levels., Competing Interests: None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Background: Aim of this study was to report on indications and clinical outcomes of patients who underwent subsequent open-cardiac surgery after transcatheter aortic valve implantation TAVI., Methods: Between 01/2011 and 12/2020 our centre performed 4043 TAVI procedures. Twenty-seven patients (including patients in whom TAVI was performed in other centres) underwent subsequent open-heart surgery via cardiopulmonary bypass. Demographic, intraprocedural data, indications for, and outcomes after surgery were evaluated., Results: Indications for cardiac surgery (aged 79 [IQR 76-84]; 59.3% male) were endocarditis (n = 11; 40.7%), annular rupture, severe paravalvular leak and severe stenosis in three (11.1%) patients, respectively as well as in one patient each (3.7%) severe tricuspid valve regurgitation, valve thrombosis, valve malposition, valve migration, ostial right coronary artery obstruction, left ventricular rupture and type A aortic dissection. The interval between the index TAVI procedure to open surgery was 3 months (IQR 0-26 months). Eight patients underwent emergent surgical conversions. Immediate procedural and procedural mortality was 25.9% and 40.7%, respectively and all-cause mortality was 51.9% (11/12 died for cardiovascular reasons). No disabling stroke was observed postoperatively. New permanent pacemaker implantation was required in three patients (11.1%)., Conclusions: Subsequent open-cardiac surgery after TAVI is rare, but may urgently become necessary due to TAVI related complications or progressing other cardiac pathologies. Despite a substantial early attrition rate clinical outcome is acceptable and a relevant number of these high-risk patients can be discharged even after emergency conversions. The option of subsequent surgical conversion remains., (© 2022 The Authors. Journal of Cardiac Surgery published by Wiley Periodicals LLC.)

Stroke, thromboembolism, and bleeding are the most recognized complications associated with pediatric ventricular assist devices (VADs) and the leading cause of death and disability on VAD support. Recently, newer antithrombotic strategies like bivalirudin have emerged that appear to be associated with a reduction in the neurologic event rates, especially for smaller pediatric-specific VADs like the Berlin Heart and PediMag/CentriMag systems where the risk of stroke is the highest. While contemporary antithrombotic therapies have likely contributed to lowering adverse event rates, we speculate that clotting and bleeding adverse events may have dropped because of a variety of other seemingly small changes to antithrombotic management that are independent of the antithrombotic agents used. This view is supported by recent reports documenting low stroke rates with anticoagulants other than bivalirudin, a drug that may have a wider therapeutic window but is not available in all locations throughout the world. The primary purpose of this report is 1) to summarize contemporary antithrombotic regimens used for smaller pediatric VADs today associated with low event rates in the United States and abroad and () to review 10 practical lessons learned and pitfalls to avoid that we believe to be important to reducing bleeding and clotting events based on our collective experience managing pediatric VADs over the past 20 years irrespective of the antithrombotic agents used., Competing Interests: Disclosure: Ms. Murray and Dr. Almond have received travel support to Advanced Cardiac Therapies Improving Outcomes Network (ACTION) meetings, which is supported by Berlin Heart, Inc and Abbott, Inc. Dr. Almond served as principle investigator (PI) on the US Food and Drug Administration (FDA) Orphan Product Development grant supporting the Berlin Heart Investigational Device Exemption (IDE) Trial (RO1 FDA 00033577) and currently serves as Medical PI of the NHLBI contract supporting the PumpKIN Trial (HHS N268201200001I). The other authors have no conflicts of interest to report., (Copyright © ASAIO 2022.)

Background: Subclinical obstructive valve thrombosis after transcatheter aortic valve replacement (TAVR) is of uncertain frequency and clinical impact., Objectives: The aim of this study was to determine the effects of apixaban vs standard of care on post-TAVR valve thrombosis detected by 4-dimensional (4D) computed tomography., Methods: The randomized ATLANTIS (Anti-Thrombotic Strategy to Lower All Cardiovascular and Neurologic Ischemic and Hemorrhagic Events After Trans-Aortic Valve Implantation for Aortic Stenosis) trial demonstrated that apixaban 5 mg twice daily was not superior to standard of care (vitamin K antagonists or antiplatelet therapy) after successful TAVR and was associated with similar safety but with more noncardiovascular deaths. Three months after randomization, 4D computed tomography was proposed to all patients to determine the percentage of patients with ≥1 prosthetic valve leaflet with grade 3 or 4 reduced leaflet motion or grade 3 or 4 hypoattenuated leaflet thickening (the primary endpoint) in the intention-to-treat population., Results: Seven hundred sixty-two participants had complete multiphase datasets and were included in the 4D computed tomographic analysis. The primary endpoint occurred in 33 (8.9%) and 51 (13.0%) patients in the apixaban and standard-of-care groups, respectively. It was reduced with apixaban vs antiplatelet therapy (OR: 0.51; 95% CI: 0.30-0.86) but not vs vitamin K antagonists (OR: 1.80; 95% CI: 0.62-5.25) (P interaction  = 0.037). The composite of death, myocardial infarction, any stroke, or systemic embolism at 1 year occurred in 10.7% (n = 9 of 84) and 7.1% (n = 48 of 178) of patients with and without subclinical valve thrombosis at 90 days, respectively (HR: 1.68; 95% CI: 0.82-3.44)., Conclusions: Apixaban reduced subclinical obstructive valve thrombosis in the majority of patients who underwent TAVR without having an established indication for anticoagulation. This study was not powered for clinical outcomes. (Anti-Thrombotic Strategy After Trans-Aortic Valve Implantation for Aortic Stenosis [ATLANTIS]; NCT02664649)., Competing Interests: Funding Support and Author Disclosures Both the prespecified ATLANTIS-4D-CT study and the main ATLANTIS study were conducted under the academic leadership of the ACTION Group (www.action-groupe.org), sponsored by AP-HP and funded in part by an unrestricted grant from Bristol Myers Squibb and Pfizer. Prof Montalescot has received research funds to the institution or fees from Abbott, Amgen, AstraZeneca, Axis, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Boston Scientific, Cell Prothera, CSL Behring, Idorsia, Leo Pharma, Eli Lilly, Medtronic, Novartis, Pfizer, Quantum Genomics, Sanofi, and Terumo. Prof Collet has received research funds to the institution or fees from AstraZeneca, Boston Scientific, Bristol Myers Squibb, COR2ED, Lead-Up, Medtronic, and WebMD. Prof Silvain has received fees or contributions to transportation costs from AstraZeneca, Bayer HealthCare, Abbott Medical France, Biotronik, Boehringer Ingelheim France, CSL Behring, Gilead Science, Sanofi France, Terumo France, and Zoll; and is a stockholder in PharmaSeeds. Dr Neumann has received grants or fees from Amgen, Bayer Health Care, Biotronik, Boehringer Ingelheim, Boston Scientific, Daiichi Sankyo, Edwards Lifesciences, Ferrer, Pfizer, Novartis, Boehringer Ingelheim, GlaxoSmithKline, Abbott Vascular, and Medtronic. Dr Cequier has received grants to the institution from Abbott Vascular, Biosensors International, Boston Scientific, and Medtronic; has received fees from Amgen, Boehringer Ingelheim, Sanofi, Ferrer International; and has participated on data and safety monitoring boards or advisory boards for AstraZeneca, Biotronik, and Daiichi Sankyo. Dr Trenk has received honoraria for lectures or support for meeting attendance and travel or participation on boards from Bristol Myers Squibb Pfizer, Bayer, Novartis Pharma, Ferrer, Daiichi Sankyo, Boehringer Ingelheim, AstraZeneca, and Amgen. Dr Lefèvre has received grants to the institution, honoraria, or support from Terumo, Boston Scientific, Edwards Lifesciences, Abbott, the European Bifurcation Club, the European Association of Percutaneous Cardiovascular Interventions, EuroPCR, and Hightech. Prof Vicaut has received fees from Abbott, Amgen, Bristol Myers Squibb, Celgene, Laboratoire Français du fractionnement et des Biotechnologies, Pfizer, and Sanofi. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aims: The respective roles of oral anticoagulation or antiplatelet therapy following transcatheter aortic valve implantation (TAVI) remain debated. ATLANTIS is an international, randomized, open-label, superiority trial comparing apixaban to the standard of care., Methods and Results: After successful TAVI, 1500 patients were randomized (1:1) to receive apixaban 5 mg (2.5 mg if impaired renal function or concomitant antiplatelet therapy) (n = 749) twice daily, or standard of care (n = 751). Randomization was stratified by the need for chronic anticoagulation therapy. Standard-of-care patients received a vitamin K antagonist (VKA) (Stratum 1) or antiplatelet therapy (Stratum 2) if there was an indication for anticoagulation or not, respectively. The primary endpoint was the composite of death, myocardial infarction, stroke or transient ischaemic attack, systemic embolism, intracardiac or bioprosthesis thrombosis, deep vein thrombosis or pulmonary embolism, and life-threatening, disabling, or major bleeding over 1-year follow-up. The primary safety endpoint was major, disabling, or life-threatening bleeding. The primary outcome occurred in 138 (18.4%) and 151 (20.1%) patients receiving apixaban or standard of care, respectively [hazard ratio (HR) 0.92; 95% confidence interval (CI) 0.73-1.16] and there was no evidence of interaction between treatment and stratum (Pinteraction = 0.57). The primary safety endpoint was similar in both groups (HR 1.02; 95% CI 0.72-1.44). In Stratum 1 (n = 451), an exploratory analysis showed no difference for all endpoints between apixaban and VKA. In Stratum 2 (n = 1049), the primary outcome and primary safety endpoint did not differ, but obstructive valve thrombosis was reduced with apixaban vs. antiplatelet therapy (HR 0.19; 95% CI 0.08-0.46), while a signal of higher non-cardiovascular mortality was observed with apixaban., Conclusion: After TAVI, apixaban was not superior to the standard of care, irrespective of an indication for oral anticoagulation., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

We report on the case of a 30-month-old boy who developed severe deep cervical necrosis after bypass surgery for total cavopulmonary connection, followed by low-cardiac output and extracorporeal life support. As several bedside debridements failed to result in sufficient wound healing, a 2-stage necrectomy followed by autologous reconstruction with a free anterolateral thigh-flap was required. Due to impaired circulation, postoperative flap monitoring was extremely difficult. To ensure flap perfusion, mean arterial pressure had to be raised by catecholamines over 7 days., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Background: Calcified coronary lesions present therapeutic challenges for the interventional cardiologist, often requiring rotational atherectomy (RA)., Aims: This study aimed to develop an angiographic scoring tool to predict the need for a priori RA., Methods: A pooled analysis of the randomised ROTAXUS and PREPARE-CALC studies was carried out, (N=220 patients, N=313 lesions), by virtue of the fact that both studies made provision for crossover to RA (from balloon dilatation or modified balloon dilatation, respectively). Logistical regression techniques were employed to assess for the presence of patient- or lesion-specific factors leading to a necessity for RA. External validation was performed though retrospective calculation of the score for 192 patients who underwent bail-out RA in a single centre., Results: Lesion length (odds ratio [OR] 1.02, 95% confidence interval [CI]: 1.00-1.04 per mm, p=0.04), bifurcation lesion (OR 2.60, 95% CI: 1.27-5.30, p=0.009), vessel tortuosity >45° (OR 3.49, 95% CI: 1.73-7.03, p<0.001) and severe vessel calcification (OR 11.60, 95% CI: 3.40-39.64, p<0.001) were predictive of the need for RA in multivariate analysis. Based on the regression coefficients, a scoring system was devised. The greater the score, the more likely a lesion required RA. The scoring system performed well in the external validation cohort, with 78% of patients crossing over having a score of greater than the proposed cut-off of 3., Conclusions: We provide an angiographic scoring tool to support the expeditious use of time and resources, allowing assessment of the likelihood of success of a balloon-based strategy, or the necessity for RA.

To assess the efficacy and safety of a breakable BabyStent to treat complex aortic coarctation (CoA) in early childhood. Although recommended in several guidelines, there is no approved aortic stent for young infants, because of the dilemma between two mandatory requirements: expandable up to adult size on the one hand, and small enough to fit through a baby's femoral artery on the other. Prospective interventional, multi-center clinical trial with the breakable Osypka BabyStent® (OBS). The OBS is a low-profile, 15-mm long cobalt-chromium stent, pre-mounted on a 6 mm balloon and inserted via a 4 Fr sheath. After implantation, its diameter is adjustable from 6 to 12 mm by balloon dilation. Further dilation opens predefined joints enabling unrestricted growth. Nineteen patients (9 male), median age 112 days (range: 7-539), median body weight 5.6 kg (range: 2.4-8.4) were deemed high risk and underwent stent implantation. Of those, 74% suffered from re-CoA following surgery, 53% had additional cardiac and 21% noncardiac malformations. Our primary combined endpoint was fulfilled: All stents were implanted in the desired region, and a >50% intrastenotic diameter-extension was achieved in 15 patients (78.9%, 80% confidence interval [62.2; 90.5], 95% confidence interval [54.4; 93.9]). Secondary endpoint confirmed that the OBS fits the baby's femoral vessel diameter. All children survived the procedure and 12-month follow-up. This stent enables percutaneous stenting of complex aortic coarctation to treat high-risk newborns and infants., (© 2022 The Authors. Catheterization and Cardiovascular Interventions published by Wiley Periodicals LLC.)

Background: Constant elevations of the serum concentration of cardiac troponin T (TnT) indicate a myocardial injury that may affect the long-term outcome of transcatheter aortic valve replacement (TAVR)., Objectives: We sought to investigate the impact of pre-TAVR TnT on outcomes after TAVR during long-term follow-up., Methods: In a retrospective, observational study we compared long term outcomes after TAVR between tertiles of preinterventional high-sensitivity TnT. Systematic follow-up was performed annually for 5 years. The primary endpoint was a composite of all-cause death and any rehospitalization., Results: Between 2010 and 2018, 2,129 patients with severe aortic valve stenosis underwent TAVR at our institution (mean age 82.6 years, 57.2% female, logistic EuroSCORE 20.5 ± 15.8). Boundaries for TnT tertiles were <21 ng/L and >42 ng/L. The median follow-up was 895 days. Three-year incidences for the primary endpoint were 70.9%, 76.6%, and 81.7% in the low, middle, and high tertile (log rank p < .001). Compared with the first tertile, the corresponding adjusted hazard ratios were 1.23 (95%-CI 1.08-1.40, p < .001) and 1.50 (95%-CI 1.32-1.70, p < .001) for the second and third tertile. We found consistent differences between TnT strata for all-cause death (3-year incidences 23.3%, 33.3%, and 47.1%; adjusted p < .001) and rehospitalization (3-year incidences 64.7%, 68.7% and 72.0%; adjusted p < .001), including significant differences in deaths (p < .001). The association between TnT and outcome was independent of coronary artery disease or low aortic valve gradient., Conclusions: TnT before TAVR is strongly associated with all-cause death and rehospitalization during 3-year follow-up., (© 2021 The Authors. Catheterization and Cardiovascular Interventions published by Wiley Periodicals LLC.)

The intracardiac nervous system (IcNS), sometimes referred to as the "little brain" of the heart, is involved in modulating many aspects of cardiac physiology. In recent years our fundamental understanding of autonomic control of the heart has drastically improved, and the IcNS is increasingly being viewed as a therapeutic target in cardiovascular disease. However, investigations of the physiology and specific roles of intracardiac neurons within the neural circuitry mediating cardiac control has been hampered by an incomplete knowledge of the anatomical organisation of the IcNS. A more thorough understanding of the IcNS is hoped to promote the development of new, highly targeted therapies to modulate IcNS activity in cardiovascular disease. In this paper, we first provide an overview of IcNS anatomy and function derived from experiments in mammals. We then provide descriptions of alternate experimental models for investigation of the IcNS, focusing on a non-mammalian model (zebrafish), neuron-cardiomyocyte co-cultures, and computational models to demonstrate how the similarity of the relevant processes in each model can help to further our understanding of the IcNS in health and disease.

Objectives: We sought to assess the safety of a restrictive permanent pacemaker implantation (PPI) strategy after transcatheter aortic valve implantation (TAVI) as compared to a liberal strategy., Background: Conduction disturbances resulting in PPI are common after TAVI. However, conduction disturbances may be transient and PPI may be superfluous in some patients., Methods: Until August 2015, we performed PPI in all patients with new complete left bundle branch block (LBBB, QRS > 120 milliseconds) or higher degree atrioventricular (AV) blocks (liberal strategy). From September 2015 onwards, LBBB established an indication for PPI only in the presence of new-onset AV block (PQ > 200 milliseconds) (restrictive strategy). We analyzed the impact of the restrictive strategy on pacemaker implantation rate, duration of hospital stay, and 1-year mortality., Results: Between January 2014 and December 2016, 383 consecutive, pacemaker-naive patients underwent TAVI with the liberal PPI strategy and subsequently 384 with the restrictive strategy. The restrictive strategy significantly reduced the percentage of patients undergoing PPI before discharge (17.2% vs. 38.1%, p < .001) and length of hospital stay (intensive care unit 52 ± 55 vs. 60 ± 52 hours, p < .001; general ward 10.6 ± 5.7 vs. 11.5 ± 5.7 days, p = .001). One-year all-cause mortality was not significantly different between groups (14.1% vs. 11.7%, log-rank p = .28). However, sudden death was more frequent in the restrictive group (3.4% vs. 1.3%, log-rank p = .049)., Conclusions: As compared to a liberal indication for PPI, a restrictive indication reduced PPI rate and length of hospital stay without significantly affecting all-cause mortality. The observed increase in the risk of sudden death with the restrictive PPI indication deserves further investigation., (© 2020 The Authors. Pacing and Clinical Electrophysiology published by Wiley Periodicals LLC.)

The heart is vital for biological function in almost all chordates, including humans. It beats continually throughout our life, supplying the body with oxygen and nutrients while removing waste products. If it stops, so does life. The heartbeat involves precise coordination of the activity of billions of individual cells, as well as their swift and well-coordinated adaption to changes in physiological demand. Much of the vital control of cardiac function occurs at the level of individual cardiac muscle cells, including acute beat-by-beat feedback from the local mechanical environment to electrical activity (as opposed to longer term changes in gene expression and functional or structural remodeling). This process is known as mechano-electric coupling (MEC). In the current review, we present evidence for, and implications of, MEC in health and disease in human; summarize our understanding of MEC effects gained from whole animal, organ, tissue, and cell studies; identify potential molecular mediators of MEC responses; and demonstrate the power of computational modeling in developing a more comprehensive understanding of ‟what makes the heart tick.ˮ.

Aims: Patients with heart failure (HF) have impaired quality of life (QoL). The randomized controlled trial PHARM-CHF investigated whether an interdisciplinary intervention consisting of regular contacts with the community pharmacy and weekly dosing aids improves medication adherence in patients with HF. It is unknown how an intervention involving frequent structured pharmacy visits affects QoL. Our aim was to explore adherence to the intervention and effects on QoL., Methods and Results: Among 237 patients, n = 110 were randomized to pharmacy care and n = 127 to usual care. The pharmacy care group received a medication review followed by (bi-)weekly dose dispensing and counselling. The median follow-up was 2.0 years [inter-quartile range (IQR) 1.2-2.7]. Median interval between pharmacy visits was 8.4 days (IQR 8.0-10.3) and the visits lasted in median 14 min (IQR 10-15). Median adherence to the intervention was 96% (IQR 84-100). QoL at 365 days was predefined as a main secondary and at 730 days as another secondary endpoint in PHARM-CHF. QoL was measured by the Minnesota Living with Heart Failure Questionnaire; and for 111 patients (n = 47 in the pharmacy care group and n = 64 in the usual care group), data were available at baseline, and after 365 and 730 days (mean age 74 years; 41% female). Improvement in QoL was numerically higher in the pharmacy care group after 365 days and was significantly better after 730 days (difference in total scores -7.7 points [-14.5 to -1.0]; P = 0.026) compared to the usual care group. In all subgroups examined, this treatment effect was preserved. Improvements in the physical and emotional dimensions were numerically higher in the pharmacy care group after 365 days and were significantly better after 730 days: -4.0 points [-6.9 to -1.2]; P = 0.006, and -1.9 points [-3.7 to -0.1]; P = 0.039, respectively., Conclusions: A pharmacy-based interdisciplinary intervention was well received by the patients and suggests clinically important improvements in QoL., (© 2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.)

Background: The study sought to learn about incidence and reasons for distal stent graft-induced new entry (dSINE) after thoracic endovascular aortic repair (TEVAR) or after frozen elephant trunk (FET) implantation, and develop prevention algorithms., Methods: In an analysis of an international multicenter registry (EuREC [European Registry of Endovascular Aortic Repair Complications] registry), we found 69 dSINE patients of 1430 (4.8%) TEVAR patients with type B aortic dissection and 6 dSINE patients of 100 (6%) patients after the FET procedure for aortic dissection with secondary morphological comparison., Results: The underlying aortic pathology was acute type B aortic dissection in 33 (44%) patients, subacute or chronic type B aortic dissection in 34 (45%) patients, acute type A aortic dissection in 3 patients and remaining dissection after type A repair in 3 (8%) patients, and acute type B intramural hematoma in 2 (3%) patients. dSINE occurred in 4.4% of patients in the acute setting and in 4.9% of patients in the subacute or chronic setting after TEVAR. After the FET procedure, dSINE occurred in 5.3% of patients in the acute setting and in 6.5% of patients in the chronic setting. The interval between TEVAR or FET and the diagnosis of dSINE was 489 ± 681 days. Follow-up after dSINE was 1340 ± 1151 days, and 4 (5%) patients developed recurrence of dSINE. Morphological analysis between patients after TEVAR with and without dSINE showed a smaller true lumen diameter, a more accentuated oval true lumen morphology, and a higher degree of stent graft oversizing in patients who developed dSINE., Conclusions: dSINE after TEVAR or FET is not rare and occurs with similar incidence after acute and chronic aortic dissection (early and late). Avoiding oversizing in the acute and chronic settings as well as carefully selecting patients for TEVAR in postdissection aneurysmal formation will aid in reducing the incidence of dSINE to a minimum., (Copyright © 2020 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Antiplatelet response to clopidogrel shows wide variation, and poor response is correlated with adverse clinical outcomes. CYP2C19 loss-of-function alleles play an important role in this response, but account for only a small proportion of variability in response to clopidogrel. An aim of the International Clopidogrel Pharmacogenomics Consortium (ICPC) is to identify other genetic determinants of clopidogrel pharmacodynamics and clinical response. A genomewide association study (GWAS) was performed using DNA from 2,750 European ancestry individuals, using adenosine diphosphate-induced platelet reactivity and major cardiovascular and cerebrovascular events as outcome parameters. GWAS for platelet reactivity revealed a strong signal for CYP2C19*2 (P value = 1.67e-33). After correction for CYP2C19*2 no other single-nucleotide polymorphism reached genomewide significance. GWAS for a combined clinical end point of cardiovascular death, myocardial infarction, or stroke (5.0% event rate), or a combined end point of cardiovascular death or myocardial infarction (4.7% event rate) showed no significant results, although in coronary artery disease, percutaneous coronary intervention, and acute coronary syndrome subgroups, mutations in SCOS5P1, CDC42BPA, and CTRAC1 showed genomewide significance (lowest P values: 1.07e-09, 4.53e-08, and 2.60e-10, respectively). CYP2C19*2 is the strongest genetic determinant of on-clopidogrel platelet reactivity. We identified three novel associations in clinical outcome subgroups, suggestive for each of these outcomes., (© 2020 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Antiplatelet therapy for patients with coronary artery disease has evolved dramatically over the last decade. P2Y12 inhibitors offering more potent and consistent platelet inhibition than clopidogrel are now widely available, dual antiplatelet therapy (DAPT) duration can be tailored to individual ischemic and bleeding risks, and strategies to personalize antiplatelet therapy have been developed when concomitant oral anticoagulation (OAC) is indicated. Scientific societies from Canada, the United States, and Europe have all published updated recommendations addressing antiplatelet therapy in the recent years. The purpose of this review is to put the Canadian guidelines into perspective vis-à-vis international recommendations by highlighting similarities and critically analyzing differences. We focus on 3 major topics relevant for clinical practice: DAPT duration following drug-eluting stent implantation, DAPT following percutaneous coronary intervention in patients with concomitant indications for OAC, and DAPT management for noncardiac surgery following drug-eluting stent implantation. Although guidelines broadly agree on the majority of recommendations, the justifications for major differences were contrasted in the manuscript. Unanswered questions remain, including the place of aspirin in secondary prevention of coronary artery disease in the contemporary era, aspirin-free strategies early after percutaneous coronary intervention, and the safe minimal duration of DAPT with newer generation stents., (Copyright © 2019 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Differences in the benefits of conscious sedation (CS) and general anesthesia (GA) during transfemoral aortic valve implantation (TAVI) are unclear.We aimed to assess differences in procedural and clinical outcomes based on the type of anesthesia received during TAVI.We analyzed SOURCE 3 Registry data for patients who received the SAPIEN 3 valve by type of anesthesia used during TAVI.Of the 1694 TAVI patients, 1027 received CS and 667 received GA. Patients were similar at baseline (81.5 years; Society of Thoracic Surgeons risk score 7.0). Compared with the GA group, the CS group had fewer intra-procedural transesophageal echocardiography (TEE) and post implantation dilatations performed, and less contrast medium was used. The CS group had significantly less kidney injury at 7 days post-procedure than the GA group (0.4% versus 1.5%, P = 0.014). Moderate paravalvular leaks (PVL) occurred more frequently in the CS group versus the GA group (2.2% versus 0.8%; P = 0.041). No severe PVL were reported. Median total hospital length of stay (LOS) after TAVI was 10 days in the CS group and 11 days in the GS group. At 30 days, all-cause death was 2.1% in CS and 1.7% in GS (P = 0.47), and myocardial infarction was 0.2% in CS and 0.1% in GS (P = 0.83).Our analyses found no significant major outcome differences between CS and GA during TAVI.

Objectives: The aim of this study was to compare clinical outcomes of different bifurcation percutaneous coronary intervention (PCI) techniques., Background: Despite several randomized trials, the optimal PCI technique for bifurcation lesions remains a matter of debate. Provisional stenting has been recommended as the default technique for most bifurcation lesions. Emerging data support double-kissing crush (DK-crush) as a 2-stent technique., Methods: PubMed and Scopus were searched for randomized controlled trials comparing PCI bifurcation techniques for coronary bifurcation lesions. Outcomes of interest were major adverse cardiovascular events (MACE). Secondary outcomes of interest were cardiac death, myocardial infarction, target vessel or lesion revascularization, and stent thrombosis. Summary odds ratios (ORs) were estimated using Bayesian network meta-analysis., Results: Twenty-one randomized controlled trials including 5,711 patients treated using 5 bifurcation PCI techniques were included. Investigated techniques were provisional stenting, T stenting/T and protrusion, crush, culotte, and DK-crush. Median follow-up duration was 12 months (interquartile range: 9 to 36 months). When all techniques were considered, patients treated using the DK-crush technique had less occurrence of MACE (OR: 0.39; 95% credible interval: 0.26 to 0.55) compared with those treated using provisional stenting, driven by a reduction in target lesion revascularization (OR: 0.36; 95% credible interval: 0.22 to 0.57). No differences were found in cardiac death, myocardial infarction, or stent thrombosis among analyzed PCI techniques. No differences in MACE were observed among provisional stenting, culotte, T stenting/T and protrusion, and crush. In non-left main bifurcations, DK-crush reduced MACE (OR: 0.42; 95% credible interval: 0.24 to 0.66)., Conclusions: In this network meta-analysis, DK-crush was associated with fewer MACE, driven by lower rates of repeat revascularization, whereas no significant differences among techniques were observed for cardiac death, myocardial infarction, and stent thrombosis. A clinical benefit of 2-stent techniques was observed over provisional stenting in bifurcation with side branch lesion length ≥10 mm., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

The coronavirus disease 2019 (COVID-19) pandemic poses an unprecedented challenge to healthcare worldwide. The infection can be life threatening and require intensive care treatment. The transmission of the disease poses a risk to both patients and healthcare workers. The number of patients requiring hospital admission and intensive care may overwhelm health systems and negatively affect standard care for patients presenting with conditions needing emergency interventions. This position statements aims to assist cardiologists in the invasive management of acute coronary syndrome (ACS) patients in the context of the COVID-19 pandemic. To that end, we assembled a panel of interventional cardiologists and acute cardiac care specialists appointed by the European Association of Percutaneous Cardiovascular Interventions (EAPCI) and from the Acute Cardiovascular Care Association (ACVC) and included the experience from the first and worst affected areas in Europe. Modified diagnostic and treatment algorithms are proposed to adapt evidence-based protocols for this unprecedented challenge. Various clinical scenarios, as well as management algorithms for patients with a diagnosed or suspected COVID-19 infection, presenting with ST- and non-ST-segment elevation ACS are described. In addition, we address the need for re-organization of ACS networks, with redistribution of hub and spoke hospitals, as well as for in-hospital reorganization of emergency rooms and cardiac units, with examples coming from multiple European countries. Furthermore, we provide a guidance to reorganization of catheterization laboratories and, importantly, measures for protection of healthcare providers involved with invasive procedures., (This article has been co-published with permission in the European Heart Journal and EuroIntervention. All rights reserved. © 2020 European Society of Cardiology. These articles are identical except for minor stylistic and spelling differences in keeping with each journal's style. Either citation can be used when citing this article.)

Research software has become a central asset in academic research. It optimizes existing and enables new research methods, implements and embeds research knowledge, and constitutes an essential research product in itself. Research software must be sustainable in order to understand, replicate, reproduce, and build upon existing research or conduct new research effectively. In other words, software must be available, discoverable, usable, and adaptable to new needs, both now and in the future. Research software therefore requires an environment that supports sustainability. Hence, a change is needed in the way research software development and maintenance are currently motivated, incentivized, funded, structurally and infrastructurally supported, and legally treated. Failing to do so will threaten the quality and validity of research. In this paper, we identify challenges for research software sustainability in Germany and beyond, in terms of motivation, selection, research software engineering personnel, funding, infrastructure, and legal aspects. Besides researchers, we specifically address political and academic decision-makers to increase awareness of the importance and needs of sustainable research software practices. In particular, we recommend strategies and measures to create an environment for sustainable research software, with the ultimate goal to ensure that software-driven research is valid, reproducible and sustainable, and that software is recognized as a first class citizen in research. This paper is the outcome of two workshops run in Germany in 2019, at deRSE19 - the first International Conference of Research Software Engineers in Germany - and a dedicated DFG-supported follow-up workshop in Berlin., Competing Interests: No competing interests were disclosed., (Copyright: © 2021 Anzt H et al.)

Background: Primary carnitine deficiency due to mutations in the SLC22A5 gene is a rare but well-treatable metabolic disorder that puts patients at risk for metabolic decompensations, skeletal and cardiac myopathy and sudden cardiac death., Results: We report on a 7-year-old boy diagnosed with primary carnitine deficiency 2 years after successful heart transplantation thanks his younger sister's having been identified via expanded newborn screening during a pilot study evaluating an extension of the German newborn screening panel., Conclusion: As L-carnitine supplementation can prevent and mostly reverse clinical symptoms of primary carnitine deficiency, all patients with cardiomyopathy should be investigated for primary carnitine deficiency even if newborn screening results were unremarkable.