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The Arctic Council working group, the Conservation of Arctic Flora and Fauna (CAFF) established the Circumpolar Biodiversity Monitoring Programme (CBMP), an international network of scientists, governments, Indigenous organizations, and conservation groups working to harmonize and integrate efforts to extend and develop monitoring and assessment of the Arctic’s biodiversity. Its relevance stretches beyond the Arctic to a broad range of regional and global initiatives and agreements. This paper describes the process and approach taken in the last two decades to develop and implement the CBMP. It documents challenges encountered, lessons learnt, and solutions, and considers how it has been a model for national, regional, and global monitoring programmes; explores how it has impacted Arctic biodiversity monitoring, assessment, and policy and concludes with observations on key issues and next steps. The following are overarching prerequisites identified in the implementation of the CBMP: effective coordination, sufficient and sustained funding, improved standards and protocols, co-production of knowledge and equitable involvement of IK approaches, data management to facilitating regional analysis and comparisons, communication and outreach to raising awareness and engagement in the programme, ensuring resources to engage in international fora to ensuring programme implementation.

Abstract: The article explores a gendered perspective on Norwegian TV-media production and representation of mens team handball. A discourse analysis, influenced by Connell (2005), Bourdieu (1997) and Messner (2002), is applied and the concepts anomaly and liminality are utilized to analyse the commentators production of the «warrior» handball athlete.

Norges Idrettsforbund og Olympiske og Paralympiske Komité (NIF) har en uttalt målsetting om en åpen og inkluderende idrett. Hvordan kommer dette til uttrykk i den praktiske virksomheten? Denne artikkelen, som bygger på data fra en undersøkelse om likestilling og mangfold i den organiserte idretten (NIF), retter søkelyset mot arbeid med inklusjon av ungdom med minoritetsbakgrunn på ulike organisasjonsnivå i NIF: særforbund, idrettskretser og idrettslag. Datamaterialet er kvalitative intervju med representanter fra ulike organisasjonsnivå. Resultatene viser at NIFs overordnede politikk i varierende grad nedfelles i særforbundenes virksomhet, i idrettskretsene og i idrettslagene. Av særforbundene skiller Fotballforbundet og Klatreforbundet seg ut som aktive pådrivere i arbeidet med inkludering. Mange idrettslag oppfattet slike spørsmål som lite aktuelle i sitt rekrutteringsområde. Representanter for lag som hadde erfaring med inkludering og rekruttering av minoritetsungdom, tilkjennega varierte erfaringer og synspunkter.

Aims: The aim of this study is to evaluate and compare the impact of the bicaval technique versus the biatrial technique (by Lower and Shumway) in paediatric heart transplant patients. Only a few studies investigate this matter regarding the long-term outcome after paediatric heart transplantation. We compared the two surgical methods regarding survival, the necessity of pacemaker implantation., Methods and Results: All 134 patients (aged <18 years) - (group-1) biatrial (n = 84), versus (group-2) bicaval (n = 50), who underwent heart transplantation between October 1988 and December 2021, were analysed. Freedom from events were estimated using the Kaplan-Meier method. Potential differences were analysed using the log rank test and Cox proportional hazard models. Mean ± standard deviation: Bypass time (per minutes) was higher in the group 1 as compared with group 2 (P = 0.050). Survival was not significantly different (P = 0.604) in either groups. Eighteen patients required permanent pacemaker implantation in the group 1 and only one patient required it in the group 2 (P = 0.001)., Conclusions: Paediatric heart transplantation using bicaval technique results similar long-term survival compared with the biatrial technique. The incidence of atrial rhythm disorders was significantly higher in the biatrial group, requiring a higher frequency of pacemaker implantation in this group. As a results, the bicaval technique has replaced the biatrial technique in our centre., (© 2024 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Preoperative calculations showed that the 9-mm inlet, 6-mm outlet, 25-cc pump chambers and 65-73 bpm would be optimal for a 5-year-old patient suffering from restrictive cardiomyopathy, with a body surface area of 0.59 m2 (1.5 L/min flow for a cardiac index of 2.5). After re-sternotomy and standard bicaval cannulation for cardiopulmonary bypass, the procedure was performed under normothermic conditions and on the beating heart. Biventricular support was established with the Berlin Heart Excor using biatrial cannulation. For left atrial cannulation, induced ventricular fibrillation was used. The 9-mm inlet cannulas were inserted into the left and right atria, respectively. The 6-mm outlet cannulas were implanted using 8-mm interposition vascular grafts for the aorta and the main pulmonary artery, respectively. Cannulas were tunnelled through the epigastric space, with systems crossing outside of the body. The 25-cc chambers were used for both right ventricular assist device and left ventricular assist device support, which subsequently showed full emptying and filling., (© The Author 2024. Published by MMCTS on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: Long-term outcomes of valve-sparing aortic root replacement (VSARR) with reimplantation vs remodeling in patients undergoing aortic root surgery remains a controversial subject., Methods: This study was a pooled meta-analysis of Kaplan-Meier-derived data from comparative studies published by December 31, 2022., Results: Fifteen studies met our eligibility criteria, comprising 3044 patients (1991 in the reimplantation group and 2018 in the remodeling group). Patients who underwent VSARR with remodeling had a higher risk of all-cause death (hazard ratio [HR], 1.54; 95% CI, 1.16-2.03; P = .002, log-rank test P < .001). Landmark analysis (with 4 years as the landmark time point) demonstrated that survival was lower in patients who underwent VSARR with remodeling (HR, 2.15; 95% CI, 1.43-3.24; P < .001) in the first 4 years. Beyond the 4-year time point, no difference in survival was observed (HR, 1.04; 95% CI, 0.72-1.50; P = .822). The risk for need of aortic valve and/or root reintervention was higher in patients undergoing VSARR with remodeling (HR, 1.49; 95% CI, 1.07-2.07; P = .019, log-rank test P < .001). We did not find statistically significant coefficients for the covariates of age, female sex, connective tissue disorders, bicuspid aortic valve, aortic dissection, coronary bypass surgery, total arch replacement, or annular stabilization, which means that these covariates did not modulate the effects observed in our pooled analyses., Conclusions: VSARR with reimplantation is associated with better overall survival and lower risk of need for reintervention over time compared with VSARR with remodeling. Regarding overall survival, we observed a time-varying effect that favored the reimplantation technique up to 4 years of follow-up, but not beyond this time point., (Copyright © 2024 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background:  Extracorporeal membrane oxygenation (ECMO) can influence pharmacokinetics. We investigated the vancomycin dosage in children on ECMO compared to critically ill children to determine the necessary dosage adjustment on ECMO., Methods:  Eight-year, single-center, retrospective cohort study at a tertiary heart center's pediatric cardiac intensive care unit (ICU) of children undergoing ECMO support. Our control group (non-ECMO) was critically ill children with delayed sternal closure after cardiac surgery. We included consecutively all children undergoing vancomycin administration. The starting dose was 10 to 15 mg/kg BW per dose, every 8 to 12 hours depending on age. The vancomycin trough level was maintained in the 10 to 20 μg/ml range., Results:  85 total courses on ECMO and 99 non-ECMO courses were included. The ECMO group's daily vancomycin dose was significantly lower than non-ECMO's at a median of 33.3 and 38.5 mg/kg/d, respectively ( p  < 0.001). Vancomycin serum trough levels were similar between groups and within the target range. The ECMO group's daily vancomycin dose dropped faster over time, with a dose on day 3 of 28.7 and 33.7 mg/kg/d, respectively. The impact of renal function on vancomycin dosing was more apparent in the ECMO group. If the renal function was reduced at the start of treatment, the vancomycin dose was lower in the ECMO group compared to the non-ECMO group with renal impairment (22.5 vs. 42.1 mg/kg/d; p  < 0.001). When renal function was normal, the doses were similar between groups., Conclusion:  In children on ECMO with impaired renal function at treatment initiation, lower vancomycin doses were necessary. Early therapeutic drug monitoring, even before reaching a steady state, should be considered., 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/).)

Objectives: The objective of the study was to improve postoperative risk assessment in congenital heart surgery by developing a machine-learning model based on readily available peri- and postoperative parameters., Methods: Our bicentric retrospective data analysis from January 2014 to December 2019 of established risk parameters for dismal outcome was used to train and test a model to predict postoperative survival within the first 30 days. The Freiburg training data consisted of 780 procedures; the Heidelberg test data comprised 985 procedures. STAT mortality score, age, aortic cross-clamp time and postoperative lactate values over 24 h were considered., Results: Our model showed an area under the curve (AUC) of 94.86%, specificity of 89.48% and sensitivity of 85.00%, resulting in 3 false negatives and 99 false positives.The STAT mortality score and the aortic cross-clamp time each showed a statistically highly significant impact on postoperative mortality. Interestingly, a child's age was barely statistically significant. Postoperative lactate values indicated an increased mortality risk if they were either constantly at a high level or low during the first 8 h postoperatively with an increase afterwards.When considering parameters available before, at the end of and 24 h after surgery, the predictive power of the complete model achieved the highest AUC. This, compared to the already high predictive power alone (AUC 88.9%) of the STAT mortality score, translates to an error reduction of 53.5%., Conclusions: Our model predicts postoperative survival after congenital heart surgery with great accuracy. Compared with preoperative risk assessments, our postoperative risk assessment reduces prediction error by half. Heightened awareness of high-risk patients should improve preventive measures and thus patient safety., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

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.)

Aims: The present study aims to characterize the genetic risk architecture of bicuspid aortic valve (BAV) disease, the most common congenital heart defect., Methods and Results: We carried out a genome-wide association study (GWAS) including 2236 BAV patients and 11 604 controls. This led to the identification of a new risk locus for BAV on chromosome 3q29. The single nucleotide polymorphism rs2550262 was genome-wide significant BAV associated (P = 3.49 × 10-08) and was replicated in an independent case-control sample. The risk locus encodes a deleterious missense variant in MUC4 (p.Ala4821Ser), a gene that is involved in epithelial-to-mesenchymal transformation. Mechanistical studies in zebrafish revealed that loss of Muc4 led to a delay in cardiac valvular development suggesting that loss of MUC4 may also play a role in aortic valve malformation. The GWAS also confirmed previously reported BAV risk loci at PALMD (P = 3.97 × 10-16), GATA4 (P = 1.61 × 10-09), and TEX41 (P = 7.68 × 10-04). In addition, the genetic BAV architecture was examined beyond the single-marker level revealing that a substantial fraction of BAV heritability is polygenic and ∼20% of the observed heritability can be explained by our GWAS data. Furthermore, we used the largest human single-cell atlas for foetal gene expression and show that the transcriptome profile in endothelial cells is a major source contributing to BAV pathology., Conclusion: Our study provides a deeper understanding of the genetic risk architecture of BAV formation on the single marker and polygenic level., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: The charity organization Kinderherzen retten e.V. (KHR) enables humanitarian congenital heart surgery for pediatric patients from low- and middle-income countries at the University Heart Center Freiburg, Germany. The aim of this study was to assess periprocedural and mid-term outcomes of these patients for evaluation of KHR sustainability. Methods: Part one of the study comprised retrospective medical chart analyses of the periprocedural course of all KHR-treated children from 2008 to 2017, and part two a prospective evaluation of their mid-term outcome, assessed by questionnaires concerning survival, medical history, mental and physical development, and socioeconomic situation. Results: Of the 100 consecutively presented children from 20 countries (median age 3.25 years), 3 patients were not invasively treatable, 89 underwent cardiovascular surgery, and 8 received a catheter intervention only. There were no periprocedural deaths. Median postoperative duration of mechanical ventilation, intensive care stay, and total hospital stay was 7 (interquartile range [IQR] 4-21) hours, 2 (IQR 1-3) days, and 12 (IQR 10-16) days, respectively. Mid-term postoperative follow-up demonstrated a 5-year survival probability of 94.4%. The majority of patients received continued medical care in their home country (86.2% of patients), were in good mental and physical condition (96.5% and 94.7% of patients, respectively), and able to engage in age-appropriate education/employment (98.3% of patients). Conclusions: Cardiac, neurodevelopmental, and socioeconomic outcomes of patients treated via KHR was satisfactory. Thorough pre-visit evaluation and close contact with local physicians are crucial when providing this high-quality, sustainable, and viable therapeutic option for these patients.

Background: Congenital heart anomalies are the most common type of organ malformation, affecting approximately 1% of all newborn infants. More than 90% of these children now survive into adulthood. They need to be cared for by specialists for adults with congenital heart disease (ACHD), as well as by family physicians, internists, and cardiologists who are adequately versed in the basic management of persons with this lifelong condition., Methods: This review is based on pertinent publications retrieved by a selective literature search, including guidelines and consensus statements from Germany and abroad., Results: Cardiovascular malformations cover a very wide spectrum, and the evidence base for the treatment of older patients with these conditions is scant. Congestive heart failure, arrhythmias, and the sequelae of pulmonary arterial hypertension are the main contributors to cardiac morbidity and mortality. Preg - nancy counseling, endocarditis prophylaxis, vaccinations, and psychosocial aspects must be targeted to each individual patient. Neither the affected patients nor their family physicians are yet adequately acquainted with the recently created care structures for this patient group., Conclusion: The care of ACHD is a multidisciplinary task that requires basic care by primary care physicians as well as the involvement of specialized cardiologists in order to ensure optimal individualized treatment.

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/).)

Objectives: We aimed to determine whether non-A non-B aortic dissection (AD) differs in morphologic and haemodynamic properties from type B AD., Methods: We simulated and compared haemodynamics of patients with acute type B or acute non-A non-B AD by means of computational fluid dynamics. Wall pressure and wall shear stress (WSS) in both the true lumen (TL) and false lumen (FL) at early, mid- and late systole were evaluated. Morphology, WSS and the FL/TL wall pressure ratio were compared between groups., Results: Nineteen patients (type B, n = 7; non-A non-B, n = 12) were included. The median age (51 [46, 67] vs 53 [50, 63] years; P = 0.71) and a complicated course (14% vs 33%; P = 0.6) did not differ between the type B group and the non-A non-B group. However, the median entry tear width was increased in the non-A non-B group (9.7 [7.3, 12.7] vs 16.3 [11.9, 24.9] mm; P = 0.010). Streamlines showed, in patients with non-A non-B AD, blood from the TL flowed into the FL via the entry tear. Prevalence of a FL/TL wall pressure ratio >1.0 (type B versus non-A non-B) at early, mid- and late systole was 57% vs 83% (P = 0.31), 43% vs 83% (P = 0.13) and 57% vs 75% (P = 0.62), respectively. WSS did not differ between the groups., Conclusions: The increased FL/TL wall pressure ratio observed during systole in non-A non-B AD may beget a complicated presentation., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

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.)

Objectives: Transposition of the great arteries with ventricular septal defect (VSD) and left ventricular outflow tract obstruction (LVOTO) is a rare malformation. Our objective was to report on management and results of the cohort with non-committed VSD from a national registry for congenital heart disease., Methods: Multicentre data were screened in the German National Registry for Congenital Heart Defects (Berlin, Germany) for repairs of transposition of the great arteries-VSD-LVOTO. A subgroup of patients with a remote/non-committed VSD was identified. End points included survival, reoperation and a composite of reoperations for LVOTO-/VSD- or baffle-related problem., Results: N = 47 patients were identified treated in 14 different national centres between 1984 and 2020. The mean age was 14 (standard deviation 9) months, ranging from 7 days to 9.5 years. Nine patients (19%) were treated as neonates, 21 (45%) as infants and 17 children (36%) beyond the age of 1 year. Survival was >90% (80-100%) at 20 years. Freedom from any reoperation was 30% (10-50%) at 20 years. Freedom from the composite end point was 72% (50-90%) at 20 years. Patients after Rastelli underwent more reoperations compared to those without intraventricular baffle (freedom from reoperation 14% vs 50%, P = 0.1). The rates of the composite end point were similar when comparing Rastelli to other techniques (63% vs 83%, P = 0.32)., Conclusions: The Rastelli operation yields robust results in the setting of non-committed VSD. Late results after neonatal arterial switch operation are outstanding. If LVOTO is not resectable and neonatal arterial switch operation suboptimal, interim palliation does not negatively impact outcome, patients can be safely delayed to beyond 1 year of age., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: The objective was to provide initial data from our prospective valve-sparing aortic root replacement (V-SARR) registry and reasons for conversion to prosthetic aortic valve replacement., Methods: Six centers established an intention-to-treat-design V-SARR-registry (the German Aortic Root Repair Registry; first patient in October 2016); the main inclusion criterion was being scheduled for V-SARR as plan A. Clinical information, operative details, intraoperative valve/root measurements, and clinical and transthoracic echocardiography follow-up-data are documented., Results: Of a total of 449 patients, we report data for 401 (81% male; mean age 51 ± 14 years). Overall, 350 patients underwent V-SARR as scheduled, group A (David variants I 55%, III 2%, IV 13%, V 24%, V-Stanford 2%, and Yacoub remodeling 2%); and 51 were converted to aortic valve replacement (group B). Median follow-up was 11 months (range, 0 to 2.6 years), cumulative follow-up was 279 patient-years. In group B, there were fewer connective tissue disorders (6% vs 16%), fewer patients had left ventricular ejection fraction greater than 50% (60% vs 90%), more had bicuspid aortic valves (45% vs 28%), and fewer patients had preoperative none/trace aortic regurgitation (2% vs 20%). Fewer patients in group B had rare types of bicuspid aortic valve (fused N/L, R/N, 10% vs 30%) and more had unbalanced roots (56% vs 40%). Immediate postoperative aortic regurgitation was none/trace in 79% and mild in 20%. At 30 days, the mean transvalvular pressure gradient was 7 ± 5 mm Hg. None of the patients died in hospital; two strokes occurred. One patient needed early aortic valve replacement as redo surgery., Conclusions: The main factors causing surgeons to convert a planned V-SARR to aortic valve replacement include asymmetry of aortic valve/root, severity of aortic regurgitation, safety reasons (left ventricular ejection fraction), and bicuspid aortic valves (but not rare types). The German Aortic Root Repair Registry will help us identify the impact on long-term outcomes of preoperative and postoperative valvular anatomy and various V-SARR types., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Aims: Atrial Fibrillation (AF) is an arrhythmia of increasing prevalence in the aging populations of developed countries. One of the important indicators of AF is sustained atrial dilatation, highlighting the importance of mechanical overload in the pathophysiology of AF. The mechanisms by which atrial cells, including fibroblasts, sense and react to changing mechanical forces, are not fully elucidated. Here, we characterise stretch-activated ion channels (SAC) in human atrial fibroblasts and changes in SAC- presence and activity associated with AF., Methods and Results: Using primary cultures of human atrial fibroblasts, isolated from patients in sinus rhythm or sustained AF, we combine electrophysiological, molecular and pharmacological tools to identify SAC. Two electrophysiological SAC- signatures were detected, indicative of cation-nonselective and potassium-selective channels. Using siRNA-mediated knockdown, we identified the cation-nonselective SAC as Piezo1. Biophysical properties of the potassium-selective channel, its sensitivity to calcium, paxilline or iberiotoxin (blockers), and NS11021 (activator), indicated presence of calcium-dependent 'big potassium channels' (BK Ca ). In cells from AF patients, Piezo1 activity and mRNA expression levels were higher than in cells from sinus rhythm patients, while BK Ca activity (but not expression) was downregulated. Both Piezo1-knockdown and removal of extracellular calcium from the patch pipette resulted in a significant reduction of BK Ca current during stretch. No co-immunoprecipitation of Piezo1 and BK Ca was detected., Conclusions: Human atrial fibroblasts contain at least two types of ion channels that are activated during stretch: Piezo1 and BK Ca . While Piezo1 is directly stretch-activated, the increase in BK Ca activity during mechanical stimulation appears to be mainly secondary to calcium influx via SAC such as Piezo1. During sustained AF, Piezo1 is increased, while BK Ca activity is reduced, highlighting differential regulation of both channels. Our data support the presence and interplay of Piezo1 and BK Ca in human atrial fibroblasts in the absence of physical links between the two channel proteins., (Copyright © 2021. Published by Elsevier Ltd.)

Cardiac fibroblasts express multiple voltage-dependent ion channels. Even though fibroblasts do not generate action potentials, they may influence cardiac electrophysiology by electrical coupling via gap junctions with cardiomyocytes, and through fibrosis. Here, we investigate the electrophysiological phenotype of cultured fibroblasts from right atrial appendage tissue of patients with sinus rhythm (SR) or atrial fibrillation (AF). Using the patch-clamp technique in whole-cell mode, we observed steady-state outward currents exhibiting either no rectification or inward and/or outward rectification. The distributions of current patterns between fibroblasts from SR and AF patients were not significantly different. In response to depolarizing voltage pulses, we measured transient outward currents with fast and slow activation kinetics, an outward background current, and an inward current with a potential-dependence resembling that of L-type Ca 2+ channels. In cell-attached patch-clamp mode, large amplitude, paxilline-sensitive single channel openings were found in ≈65% of SR and ∼38% of AF fibroblasts, suggesting the presence of "big conductance Ca 2+ -activated K + (BK Ca )" channels. The open probability of BK Ca was significantly lower in AF than in SR fibroblasts. When cultured in the presence of paxilline, the shape of fibroblasts became wider and less spindle-like. Our data confirm previous findings on cardiac fibroblast electrophysiology and extend them by illustrating differential channel expression in human atrial fibroblasts from SR and AF tissue., 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., (Copyright © 2021 Jakob, Klesen, Darkow, Kari, Beyersdorf, Kohl, Ravens and Peyronnet.)

Introduction: Spinal cord ischemia after cardiovascular interventions continues to be a devastating problem in modern surgery. The role of intraspinal vascular networks and anterior radiculomedullary arteries (ARMA) in preventing spinal cord ischemia is poorly understood., Materials and Methods: Landrace pigs (n = 30, 35.1 ± 3.9 kg) underwent a lateral thoracotomy. Fluorescent microspheres were injected into the left atrium and a reference sample was aspirated from the descending aorta. Repeated measurements of spinal cord and renal cortical blood flow from the left and right kidneys with three different microsphere colors in five pigs were taken to validate reproducibility. Spinal cord blood flow to the upper thoracic (T1-T4), mid-thoracic (T5-T8), lower thoracic (T9-T13), and lumbar (L1-L3) levels were determined. After euthanasia, we carried out selective vascular corrosion cast and counted the left and right ARMAs from levels T1-T13., Results: Blood flow analysis of the left and right kidneys revealed a strong correlation (r = .94, p < .001). We detected more left than right ARMAs, with the highest prevalence at T4 (p < .05). The mean number of ARMAs was 8 ± 2. Their number in the upper thoracic region ranged from 2 to 7 (mean of 5 ± 1), while in the lower thoracic region they ranged from 0 to 5 (mean of 3 ± 1 [p < .001])., Conclusions: This study shows that combining fluorescence microsphere technique and vascular corrosion cast is well suited for assessing the blood flow and visualizing the arteries at the same time., (© 2020 The Authors. Clinical Anatomy published by Wiley Periodicals LLC. on behalf of American Association of Clinical Anatomists.)

In search of more efficacious and safe pharmacological treatments for atrial fibrillation (AF), atria-selective antiarrhythmic agents have been promoted that target ion channels principally expressed in the atria. This concept allows one to engage antiarrhythmic effects in atria, but spares the ventricles from potentially proarrhythmic side effects. It has been suggested that cardiac small conductance Ca 2+ -activated K + (SK) channels may represent an atria-selective target in mammals including humans. However, there are conflicting data concerning the expression of SK channels in different stages of AF, and recent findings suggest that SK channels are upregulated in ventricular myocardium when patients develop heart failure. To address this issue, RNA-sequencing was performed to compare expression levels of three SK channels ( KCNN1 , KCNN2 , and KCNN3 ) in human atrial and ventricular tissue samples from transplant donor hearts (no cardiac disease), and patients with cardiac disease in sinus rhythm or with AF. In addition, for control purposes expression levels of several genes known to be either chamber-selective or differentially expressed in AF and heart failure were determined. In atria, as compared to ventricle from transplant donor hearts, we confirmed higher expression of KCNN1 and KCNA5 , and lower expression of KCNJ2 , whereas KCNN2 and KCNN3 were statistically not differentially expressed. Overall expression of KCNN1 was low compared to KCNN2 and KCNN3 . Comparing atrial tissue from patients with AF to sinus rhythm samples we saw downregulation of KCNN2 in AF, as previously reported. When comparing ventricular tissue from heart failure patients to non-diseased samples, we found significantly increased ventricular expression of KCNN3 in heart failure, as previously published. The other channels showed no significant difference in expression in either disease. Our results add weight to the view that SK channels are not likely to be an atria-selective target, especially in failing human hearts, and modulators of these channels may prove to have less utility in treating AF than hoped. Whether targeting SK1 holds potential remains to be elucidated., Competing Interests: TN, MS, and SR were employed by Amgen Inc., at the time of submission of the manuscript. 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 © 2021 Darkow, Nguyen, Stolina, Kari, Schmidt, Wiedmann, Baczkó, Kohl, Rajamani, Ravens and Peyronnet.)

Objectives: The anatomical distribution pattern of epidural intraspinal arteries is not entirely understood but is likely to substantially impact maintaining perfusion during segmental artery sacrifice when treating acute and chronic thoraco-abdominal aortic diseases. We investigated the anatomical distribution pattern of intraspinal arteries., Methods: Twenty fresh, non-embalmed cadaveric human bodies were studied. Anatomical dissection and investigation of the epidural arterial network were performed according to a standardized protocol. We used a generalized mixed linear model to test whether the presence probability for certain vessels differed between vertebrae/segments., Results: There was craniocaudal continuity of all ipsilateral longitudinal connections from T1 to L5 by the anterior radicular artery. The mean [±standard deviation (SD)] number of transverse anastomoses was 9.7 ± 2.1. The presence probability of transverse anastomoses along the spine was different between vertebrae (P < 0.0001). There were 2 distribution peaks along the spine: 1 peak around T4-T6 and 1 around T11. The mean (±SD) number of thoracic and lumbar anterior radiculomedullary arteries (ARMAs) was 3.0 ± 1.1. The probability of the presence of ARMAs along the spine was different for each vertebral segment (P < 0.0001). Between ARMAs there were gaps of up to a maximum of 9 vertebrae. All Adamkiewicz arteries were located caudally to T7. The median segment of the Adamkiewicz presence was T10/11., Conclusions: The epidural collateral network shows craniocaudal continuity. The number of transverse anastomoses is high. The number of ARMAs is low, and there is considerable variation in their distribution and offspring, which is highly likely to impact perfusion during segmental artery sacrifice when treating thoraco-abdominal aortic disease., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

The pathogenesis of ascending thoracic aortic aneurysm (aTAA) is thought to differ between patients with bicuspid aortic valve (BAV) and tricuspid aortic valve (TAV), and one of the causes is different hemodynamics. Influenced by hemodynamics, the tissue levels of proteins associated with aTAA might differ between aTAAs with BAV and TAV and between different localities within the aortic wall. We therefore analyzed aTAA tissue levels of MMP-2 (matrix metalloproteinase-2) isoforms (Pro-MMP-2, active MMP-2, and total MMP-2) and tissue levels of MMP-14, TIMP-2 (tissue inhibitor of metalloproteinase-2), MMP-9, and TIMP-1 in 19 patients with BAV and 23 patients with TAV via gelatin zymography and enzyme-linked immunosorbent assay (ELISA), respectively. TAV and BAV groups' protein levels did not differ significantly. Whereas the TAV group exhibited no significant differences in protein levels between the aneurysm's anterior and posterior parts, the BAV group revealed significantly higher levels of Pro-MMP-2, total MMP-2, and TIMP-2 in the aneurysm's posterior parts (mean Pro-MMP-2 200.52 arbitrary units (AU) versus 161.12 AU, p =0.007; mean total MMP-2 235.22 AU versus 193.68 AU, p =0.002; mean TIMP-2 26.90 ng/ml versus 25.36 ng/ml, p =0.009), whereas the other proteins did not differ significantly within the aortic wall. Thus, MMPs are distributed more heterogeneously within the aortic wall of aTAAs associated with BAV than in those associated with TAV, which is a new aspect for understanding the underlying pathogenesis. This heterogeneous protein level distribution might be attributable to differences in the underlying pathogenesis, especially hemodynamics. This result is important for further studies as it will be essential to specify the location of samples to ensure data comparability regarding the main goals of understanding the pathogenesis of aTAA, optimizing treatments, and establishing a screening method for its potentially deadly complications., Competing Interests: The authors declare that they have no conflicts of interest to declare regarding the publication of this paper., (Copyright © 2020 Ramona Schmitt et al.)

Background: In contrast to the standard cardioplegic cardiac arrest (CA), some centers prefer the beating-heart technique using selective normothermic myocardial perfusion (SMP) during aortic arch repair. The aim of this study was to evaluate myocardial injury and the need for inotropic and vasopressor support in patients undergoing total aortic arch replacement using SMP or CA during arch repair., Methods: Total arch replacement was performed in 127 patients (65 years [IQR: 56-73 years] years) between March 2013 and May 2018 via the frozen elephant trunk technique. Of those, 25 patients were operated on with selective myocardial perfusion. Blood samples and catecholamine doses were evaluated. We compared the SMP group's and CA group's outcomes., Results: The two groups' risk factors, underlying aortic pathologies, and surgical details were similar. The SMP group's intraoperative norepinephrine application rates were significantly lower than the CA group's (P=0.030), as were their postoperative norepinephrine application rates (norepinephrine: P=0.007). Postoperative cardiac enzymes tended to be lower in the SMP group; the difference in creatine-kinase MB reached statistical significance after 14 hours (P=0.024). Intensive care unit stay was significantly shorter in the SMP group (P=0.041), and in-hospital mortality was comparable (4% in the SMP and 11% in the CA group; P=0.46)., Conclusions: By applying selective normothermic myocardial perfusion, beating-heart aortic arch surgery has the potential to reduce the need for perioperative inotropes, and it might reduce myocardial injury. This approach is a potentially useful adjunct to our armamentarium, particularly in patients with preexisting myocardial damage or in conjunction of arch repair together with other cardiac procedures.

Background: Measuring transcranial motor evoked potentials (EPs) and somatosensory EPs is a well-established method to assess spinal cord function during thoracic endovascular aortic repair (TEVAR). Functional occlusion of one or both internal iliac arteries by large bore sheaths during TEVAR can cause unilateral intermittently EP loss., Methods: Between 2006 and 2016, 194 patients underwent TEVAR entailing EP monitoring. The ISIS IOM System (Inomed Medizintechnik GmbH, Emmendingen, Germany) was employed in all patients. EPs were recorded after inducing anesthesia, during the procedure, and before discontinuing anesthesia., Results: We observed a unilateral intermittently EP decrease or loss in 12 (6.2%) patients. Most events were ipsilateral (9 of 12). The underlying pathologies were descending aortic aneurysm in six patients and type B dissection in six patients. An evoked-potential decrease or loss was always associated with the insertion of large bore stent-graft-introducing sheaths. The median duration of the unilaterally EP decrease or loss was 16 (10; 31) minutes (range, 2-77 minutes) with baseline values re-established at the end of the procedure after sheath removal in all cases. No patient developed irreversible symptomatic spinal cord ischemia., Conclusion: A functional occlusion of internal iliac arteries via large bore TEVAR-introducing sheaths is associated with a unilateral intermittent decrease in or loss of EPs returning to baseline after sheath removal. This observation highlights the importance of the internal iliac arteries as one of the major spinal cord's blood supply territories, and may serve as a stimulus to reduce the duration of sheath indwelling to a minimum., Competing Interests: None declared., (Georg Thieme Verlag KG Stuttgart · New York.)

A nine-month-old girl diagnosed with anatomically corrected malposition (atrioventricular discordance, ventriculoarterial concordance, and malposed great arteries) complicated by multiple ventricular septal defects (VSD) and multifactorial left ventricular outflow tract obstruction (LVOTO) presented for management after pulmonary artery banding. She underwent interim palliation in the form of bilateral cavopulmonary connections, a modified Damus-Kaye-Stansel-type anastomosis, and subsequent staged one-and-a-half ventricle repair (1.5 repair) at the age of three years in the form of VSD closure, hemi-Mustard, and LVOTO resection.

Objectives: Neurologic damage following cardiac arrest remains a major burden for modern resuscitation medicine. Cardiopulmonary resuscitation with extracorporeal circulatory support holds the potential to reduce morbidity and mortality. Furthermore, the endogenous gasotransmitter carbon monoxide attracts attention in reducing cerebral injury. We hypothesize that extracorporeal resuscitation with additional carbon monoxide application reduces neurologic damage., Design: Randomized, controlled animal study., Setting: University research laboratory., Subjects: Landrace-hybrid pigs., Interventions: In a porcine model, carbon monoxide was added using a novel extracorporeal releasing system after resuscitation from cardiac arrest., Measurements and Main Results: As markers of cerebral function, neuromonitoring modalities (somatosensory-evoked potentials, cerebral oximetry, and transcranial Doppler ultrasound) were used. Histopathologic damage and molecular markers (caspase-3 activity and heme oxygenase-1 expression) were analyzed. Cerebral oximetry showed fast rise in regional oxygen saturation after carbon monoxide treatment at 0.5 hours compared with extracorporeal resuscitation alone (regional cerebral oxygen saturation, 73% ± 3% vs 52% ± 8%; p < 0.05). Median nerve somatosensory-evoked potentials showed improved activity upon carbon monoxide treatment, whereas post-cardiac arrest cerebral perfusion differences were diminished. Histopathologic damage scores were reduced compared with customary resuscitation strategies (hippocampus: sham, 0.4 ± 0.2; cardiopulmonary resuscitation, 1.7 ± 0.4; extracorporeal cardiopulmonary resuscitation, 2.3 ± 0.2; extracorporeal cardiopulmonary resuscitation with carbon monoxide application [CO-E-CPR], 0.9 ± 0.3; p < 0.05). Furthermore, ionized calcium-binding adaptor molecule 1 staining revealed reduced damage patterns upon carbon monoxide treatment. Caspase-3 activity (cardiopulmonary resuscitation, 426 ± 169 pg/mL; extracorporeal cardiopulmonary resuscitation, 240 ± 61 pg/mL; CO-E-CPR, 89 ± 26 pg/mL; p < 0.05) and heme oxygenase-1 (sham, 1 ± 0.1; cardiopulmonary resuscitation, 2.5 ± 0.4; extracorporeal cardiopulmonary resuscitation, 2.4 ± 0.2; CO-E-CPR, 1.4 ± 0.2; p < 0.05) expression were reduced after carbon monoxide exposure., Conclusions: Carbon monoxide application during extracorporeal resuscitation reduces injury patterns in neuromonitoring and decreases histopathologic cerebral damage by reducing apoptosis. This may lay the basis for further clinical translation of this highly salutary substance.

Background: To characterize treatment of transposition of great arteries with ventricular septal defect and left ventricular outflow tract obstruction (LVOTO) in Germany and to analyze late outcomes., Methods: German Registry for Congenital Heart Defects data were searched for transposition of great arteries with ventricular septal defect and LVOTO. One hundred thirty-nine patients were treated at 15 institutions between 1968 and 2016. Risk factor analyses were performed for the primary endpoints of death and reoperation/reintervention., Results: Follow-up was 88% complete, with a mean follow-up of 16 ± 7 years (median, 15 years [range, 1-48]) and a cumulative follow-up comprising 1739 patient-years. Atrial switches were performed in 15%, Rastelli procedure in 48%, Nikaidoh procedure in 9%, réparation a l'étage ventriculair (REV) in 8%, and arterial switch in 20%. Actuarial survival at 30 years was 86% (range, 83%-90%), with no difference between repairs. Freedom from primary reoperation was 17% (range, 12%-21%) at 30 years. Freedom from reoperation for LVOTO at 30 years was 74% (range, 70%-78%). Recurrent LVOTO was found in 9%, with risk factor diffuse subvalvular LVOTO (odds ratio, 9.8; P = .04). Late freedom from first reoperations other than right ventricle-to-pulmonary artery conduit was 60% (range, 59%-61%), with predictors multiple ventricular septal defect (hazard ratio, 6; P = .03) and Rastelli procedure (hazard ratio, 12; P = .03). Absolute reoperation rates were lowest for REV procedure (16% at a mean of 12 years)., Conclusions: Long-term survival is good without detectable differences between operations. Since the early 2000s increasing use of Nikaidoh and REV procedures was obvious, with REV performing particularly well. Surgery-specific and -unspecific reoperations are most common after the Rastelli technique., (Copyright © 2020 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Aims: Heart disease of different aetiology remains the leading cause of cardiac arrest (CA). Despite efforts to improve the quality of cardiopulmonary resuscitation (CPR), subsequent myocardial and systemic damage after CA still present a major long-term burden. Low-dose carbon monoxide (CO) is known to exert protective effects in cardiovascular pathophysiology but clinical applications are challenged by unfavourable delivery modes. We tested the hypothesis that extracorporeal resuscitation (E-CPR) in combination with controlled fast onset CO delivery results in improved cardiac physiology and haemodynamics. Damage-associated molecular pattern (DAMP) signalling may be part of the molecular mechanism., Methods and Results: In an established porcine model, E-CPR was performed. While E-CPR leads to similar results as compared to a conventional CPR strategy, CO delivery in combination with E-CPR demonstrated significant cardioprotection. Cardiac performance analysis using echocardiography and thermodilution techniques showed a CO-dependent improved cardiac function compared to severe myocardial dysfunction in CPR and E-CPR (left ventricular ejection fraction: Sham 49 ± 5; CPR 26 ± 2; E-CPR 25 ± 2; CO-E-CPR 31 ± 4; P < 0.05). While sublingual microcirculation was significantly compromised in CPR and E-CPR, CO delivery demonstrated a significant improvement in microvascular function (microvascular flow index: Sham 2.9 ± 0.1; CPR 2.2 ± 0.1; E-CPR 1.8 ± 0.1; CO-E-CPR 2.7 ± 0.1; P < 0.01). Histological and serological myocardial damage markers were significantly reduced (hsTroponin-T Sham 0.01 ± 0.001; CPR 1.9 ± 0.2; E-CPR 3.5 ± 1.2; CO-E-CPR 0.5 ± 0.2 ng/mL; P < 0.05). DAMP signalling was decreased ipse facto leading to influence of cardioprotective heat shock and cyclooxygenase response., Conclusions: CO treatment restores myocardial function and improves systemic macro- and microhaemodynamics in E-CPR through a reduction in DAMPs., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Background:  To assess risks and benefits of a standardized strategy to prevent symptomatic spinal cord ischemia (SSCI) after thoracic endovascular repair (TEVAR) using routine cerebrospinal fluid (CSF) catheter placement and evoked potential (EP) monitoring., Methods:  One hundred and ninety-five patients underwent 223 SSCI low-risk TEVAR procedures between 1998 and 2014. CSF catheter was used to measure CSF pressure and drain CSF if necessary throughout the procedure and up to 24 hours thereafter. EPs were used to monitor spinal cord integrity throughout the procedure., Results:  Underlying pathologies included descending thoracic aortic aneurysm in 115 (52%), type B aortic dissection in 85 (38%), traumatic aortic rupture in 16 (7%), and others in 7 (3%) patients. CSF catheter was inserted before TEVAR in 116 procedures (52%). Active CSF draining was required in 29 patients (25%). The CSF catheter caused no major and 11 (10%) minor complications. EP were monitored during 88 (40%) procedures. We observed a reduction in the amplitude, prolonged latencies, or complete signal loss in nine procedures. There were no EP monitoring-related complications. SSCI incidence was higher in patients without CSF drainage (0.8% vs 4.7%, p  = 0.031)., Conclusion:  Use of CSF drainage is associated with a significant lower incidence of SSCI after SSCI low-risk TEVAR than nonuse, whereas the complication rate associated with CSF drainage insertion or removal is very low. Routine EP monitoring is a useful tool to detect immediate arterial inflow obstruction to the spinal cord. The combination of these two methods serves as a safe and reliable standardized strategy in reducing the incidence of SSCI to a minimum., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (Georg Thieme Verlag KG Stuttgart · New York.)

Background: Biological heart-valve prostheses have undergone continuous devel- opment up to the present, and technological advances have been made in catheter- assisted valve systems (transcatheter aortic valve implantation, TAVI) and minimally invasive routes of application. These parallel trends have led to major changes in therapeutic strategies, widening the spectrum of patients who are candidates for biological aortic valve implantation., Methods: This review is based on pertinent publications retrieved by a systematic search in PubMed employing the search terms "conventional biological aortic pros- thesis," "rapid deployment prosthesis," and "transcatheter aortic valve implantation/ replacement.", Results: Among biological heart-valve prostheses, a distinction is drawn between stented (conventional, rapid-deployment, and catheter-assisted) and non-stented types. The long-term durability of conventional, surgically implantable biological valve protheses is by far the best documented: the reported 5-year reoperation rates range from 13.4% to 36.6%, and the pacemaker implantation rate is ca. 4%. Rapid-deployment prostheses combine the advantages of conventional and ca- theter-assisted techniques and facilitate minimally invasive approaches. The TAVI method is currently recommended for high- and intermediate-risk patients, while conventional valve replacement remains the method of choice for those at low risk. Rapid-deployment and TAVI prostheses is associated with a higher pacemaker im- plantation rate than conventional prostheses: these rates are 8.5-15.3% for TAVI and 6.0-8.8% for rapid-deployment valves. The intermediate-term durability of catheter-assisted and rapid-deployment prostheses appears promising, but their long-term durability is still unclear., Conclusion: The further development of biological heart-valve prostheses in the form of improved conventional, transcatheter, and rapid-deployment prostheses now enables individualized treatment. Before any such procedure is performed, the car- diac team must assess the patient's risk profile and the advantages and disadvan- tages of each type of prosthesis to determine which is best.

The last 15 years have overwhelmed the surgical community with a range of approaches in treating pathologies involving the aortic arch of which some are here to stay. The ones to stay are-in the authors' opinion-refined classical surgical approaches such as the frozen elephant trunk technique, near-orthotopic combined vascular and endovascular approaches such as subclavian to carotid transposition/bypass and double transposition, and finally, near-orthotopic advanced endovascular solutions such as the double-endovascular repair using fenestrated and/or branched solutions which will be the main focus of this article., Competing Interests: Conflict of interestMartin Czerny and Bartosz Rylski are consultants to Terumo Aortic.No need for ethics or consent as this is a review article., (© Indian Association of Cardiovascular-Thoracic Surgeons 2019.)

Objectives: Elevated matrix metalloproteinase-2 (MMP-2) tissue levels have been associated with ascending thoracic aortic aneurysm (aTAA). As MMP-2 activation is controlled by interactions among matrix metalloproteinase-14 (MMP-14), a tissue inhibitor of metalloproteinases-2 (TIMP-2) and Pro-MMP-2 in cell culture, this activation process might also play a role in aTAA., Methods: Via gelatin zymography we analyzed tissue levels of MMP-2 isoforms (Pro-MMP-2, active MMP-2, total MMP-2) and via enzyme-linked immunosorbent assay (ELISA,) MMP-14,TIMP-2 and total MMP-2 tissue levels in N = 42 patients with aTAA. As controls, MMP-14 and TIMP-2 aortic tissue levels in N = 9 patients undergoing coronary artery bypass surgery were measured via ELISA, and levels of MMP-2 isoforms in N = 11 patients via gelatin zymography., Results: Active MMP-2 was significantly higher in aTAA than in controls. Patients with aTAA exhibited significantly lower Pro-MMP-2 and TIMP-2 levels. Total MMP-2 and MMP-14 did not differ significantly between groups. Regression analysis revealed a linear relationship between TIMP-2 and the MMP-14/TIMP-2 ratio, as well as active MMP-2 in aTAA. Aneurysmatic tissue can be accurately distinguished from control aortic tissue (AUC = 1) by analyzing the active MMP-2/Pro-MMP-2 ratio with a cutoff value of 0.11, whereas MMP-14 and TIMP-2 roles are negligible in ROC analysis., Conclusion: A larger amount of MMP-2 is activated in aTAA than in control aortic tissue-a factor that seems to be a central process in aneurysm development. When active MMP-2 exceeds 10% compared to Pro-MMP-2, we conclude that it originates from aneurysmatic tissue, which we regard as a starting point for further studies of aTAA biomarkers. The tissue's MMP-14/TIMP-2 ratio may regulate the degree of Pro-MMP-2 activation as a determining factor, while the enzymatic activities of MMP-14 and TIMP-2 do not seem to play a key role in aneurysm development., Competing Interests: The authors have declared that no competing interests exist.

Background: Outcomes of early-onset acute type A aortic dissection (ATAAD) associated with Marfan syndrome (MFS) are known, but not with other etiologies., Methods and results: ATAAD patients from 2 centers (n=1,001) were divided into 2 groups: age ≤45 years (n=93) and age >45 years (n=908). Although in-hospital death and 10-year survival were similar (12% vs. 7% and 62.6% vs. 67.3%), the 10-year aortic event-free survival differed (50.0% vs. 80.2%; P<0.01). ATAAD patients from 3 centers (n=132), all aged ≤45 years, were divided into 5 groups: lone hypertension (HTN, n=71), MFS (n=23), non-syndromic familial thoracic aortic aneurysm and dissection (NS-FTAAD, n=16), bicuspid aortic valve (BAV, n=11), and no known etiologic factor (n=11). The incidence of severe aortic insufficiency varied between groups (HTN: 11%, MFS: 39%, NS-FTAAD: 38%, BAV: 55%, no known factor: 46%; P<0.01), whereas in-hospital death did not (14%, 22%, 0%, 0%, and 9%; P=0.061). The 10-year survival was 52.2%, 64.7%, 83.6%, 100%, and 90.9%, respectively, and 10-year aortic event-free survival was 55.6%, 36.3%, 77.5%, 90.0%, and 30.0%. Median descending aorta growth (mm/year) was 1.1 (0.1-3.4), 2.3 (0.3-5.3), 1.9 (1.3-2.7), 0.9 (-0.1-2.0), and 1.0 (-0.2-2.9) (P=0.15), respectively., Conclusions: Late aortic events are common in young ATAAD patients. Known etiologic factors, though not BAV, negatively influence late outcomes in these patients.