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Background: Cardiovascular research heavily relies on mouse (Mus musculus) models to study disease mechanisms and to test novel biomarkers and medications. Yet, applying these results to patients remains a major challenge and often results in noneffective drugs. Therefore, it is an open challenge of translational science to develop models with high similarities and predictive value. This requires a comparison of disease models in mice with diseased tissue derived from humans., Results: To compare the transcriptional signatures at single-cell resolution, we implemented an integration pipeline called OrthoIntegrate, which uniquely assigns orthologs and therewith merges single-cell RNA sequencing (scRNA-seq) RNA of different species. The pipeline has been designed to be as easy to use and is fully integrable in the standard Seurat workflow.We applied OrthoIntegrate on scRNA-seq from cardiac tissue of heart failure patients with reduced ejection fraction (HFrEF) and scRNA-seq from the mice after chronic infarction, which is a commonly used mouse model to mimic HFrEF. We discovered shared and distinct regulatory pathways between human HFrEF patients and the corresponding mouse model. Overall, 54% of genes were commonly regulated, including major changes in cardiomyocyte energy metabolism. However, several regulatory pathways (e.g., angiogenesis) were specifically regulated in humans., Conclusions: The demonstration of unique pathways occurring in humans indicates limitations on the comparability between mice models and human HFrEF and shows that results from the mice model should be validated carefully. OrthoIntegrate is publicly accessible (https://github.com/MarianoRuzJurado/OrthoIntegrate) and can be used to integrate other large datasets to provide a general comparison of models with patient data., (© The Author(s) 2024. Published by Oxford University Press GigaScience.)

Aims: Identification of high-risk patients and individualized decision support based on objective criteria for rapid discharge after transcatheter aortic valve implantation (TAVI) are key requirements in the context of contemporary TAVI treatment. This study aimed to predict 30-day mortality following TAVI based on machine learning (ML) using data from the German Aortic Valve Registry., Methods and Results: Mortality risk was determined using a random forest ML model that was condensed in the newly developed TAVI Risk Machine (TRIM) scores, designed to represent clinically meaningful risk modelling before (TRIMpre) and in particular after (TRIMpost) TAVI. Algorithm was trained and cross-validated on data of 22 283 patients (729 died within 30 days post-TAVI) and generalisation was examined on data of 5864 patients (146 died). TRIMpost demonstrated significantly better performance than traditional scores [ C -statistics value, 0.79; 95% confidence interval (CI)] [0.74; 0.83] compared to Society of Thoracic Surgeons (STS) with C -statistics value 0.69; 95%-CI [0.65; 0.74]). An abridged (aTRIMpost) score comprising 25 features (calculated using a web interface) exhibited significantly higher performance than traditional scores ( C -statistics value, 0.74; 95%-CI [0.70; 0.78]). Validation on external data of 6693 patients (205 died within 30 days post-TAVI) of the Swiss TAVI Registry confirmed significantly better performance for the TRIMpost ( C -statistics value 0.75, 95%-CI [0.72; 0.79]) compared to STS ( C -statistics value 0.67, CI [0.63; 0.70])., Conclusion: TRIM scores demonstrate good performance for risk estimation before and after TAVI. Together with clinical judgement, they may support standardised and objective decision-making before and after TAVI., Competing Interests: Conflict of interest: T Friede reports personal fees for statistical consultancies (includingdata monitoring committees) from Novartis, Bayer, Janssen, Roche, Galapagos, Penumbra, Parexel, Vifor, BiosenseWebster, CSLBehring, Fresenius Kabi, Coherex Medical, LivaNova, Minoryx, IQVIA, Enanta, Relaxera, Immunic; all outside the submitted work. CHamm reports membership in the International Strategic Advisory Board of Medtronic Inc. H Möllmann reports Speaker honoraria, advisory board and proctor fees Abbott, Boston Scientific, Edwards Lifesciences, Medtronic. S Stortecky reports research grants to theinstitution from Edwards Lifesciences, Medtronic, Abbott and Boston Scientific, and personal fees from Boston Scientific, Teleflex, and BTG. S 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. He served as advisory board member and/or member of the steering/executive group oftrials 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 personalpayments. He is also member of the steering/executive committee group of several investigator-initiated trials. G Hasenfuß reportshonorarium for consultating and/or for lectures from AstraZeneca, Bayer, Boehringer, Impulse Dynamics, Novartis, Pfizer, Servier, Viforand Consultation without honoraria from Corvia. T Seidler reports research or educational grants to the institution by Edwards LifeSciences and honoraria for lectures or advisory board consultations or travel grants from Abbott Vascular, AstraZeneca, BoehringerIngelheim, Bristol Myers Squibb, Corvia, Cytokinetics, Edwards Life Sciences, Medtronic, Myocardia, Novartis, Pfizer, Teleflex. S. Bleiziffer reports Speaker fees from Boston Scentific, Abbott, Edwards Lifesciences and Medtronic. All other authors declare no conflicts of interest exist., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Objectives: The Ascyrus Medical Dissection Stent (AMDS) has been recently introduced as an alternative for total arch replacement in acute aortic dissection type A (AADA). The aim of this study was to evaluate the postoperative outcomes after AMDS treatment in a large contemporary cohort of AADA patients., Methods: Data acquisition was performed retrospectively at 2 German aortic centres between 2020 and 2022 and comprised the perioperative parameters and postoperative results of all AADA patients. All patients treated with the AMDS for AADA were included in the study. The primary end point was in-hospital mortality. Secondary end points were defined as early postoperative and AMDS-related complications., Results: Fifty-seven AADA patients treated by AMDS were included in the study group. The mean age was 64.6 ± 10.8 years and 59.7% (n = 34) were males. The actual in-hospital mortality was considerably lower than the predicted mortality risk by the German registry for acute aortic dissection type A score (16% vs 22%). The median ICU and in-hospital stay were 5 (interquartile range: 3-13) and 12 (interquartile range: 10-22) days, respectively. Postoperative complications comprised acute renal insufficiency (37%) with need for temporary (16%) or permanent dialysis (5%), delirium (26%), re-exploration for bleeding (14%), tracheostomy (14%) and new stroke (4%). A new AMDS-related complication (central stent collapse) was observed in 9% (n = 5) by postoperative computed tomography and chest X-ray. The incidence of complete central AMDS collapse did not impact 30-day mortality., Conclusions: The AMDS may be successfully used in AADA with acceptable 30-day mortality in accordance with the German registry for acute aortic dissection type A score. However, careful preoperative evaluation of the patient's individual aortic anatomy regarding potential contraindications and proper device implantation are strongly recommended to avoid complete central AMDS collapse., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objectives: Aortic valve (AV) repair is an evolving surgical strategy in the treatment of young patients with aortic regurgitation (AR) and/or aortic root aneurysm. We aimed to determine the clinical outcome following AV repair/AV-sparing root surgery using real-world data from the German Aortic Valve Registry., Methods: A total of 2327 patients with AR (mean age 55.2 ± 15.0 years, 76% men), who underwent AV repair/AV-sparing root surgery between 2011 and 2015 (i.e. 5% of 42 868 AV surgery patients enrolled in the German Aortic Valve Registry during the same period) were included. Study cohort was subdivided according to the technique of AV repair: isolated AV repair without root surgery (group I) (n = 914), AV-sparing root surgery (i.e. reimplantation or remodelling) without cusp repair (group II) (n = 1077) and AV-sparing root surgery (i.e. reimplantation or remodelling) with simultaneous cusp repair (group III) (n = 336). Primary end point was 1-year survival after AV repair/AV-sparing root surgery. Secondary end points were freedom from cardiac adverse events and freedom from AV reinterventions at 1-year follow-up., Results: Thirty-day mortality was 19 (0.8%) in the whole study cohort without significant differences in the 3 subgroups [4 (0.4%) patients in group I vs 14 (1.3%) patients in group II vs 1 (0.3%) patient in group III (P = 0.054)]. Postoperatively, 1445 (74%) patients had no residual AR, 474 (24%) patients had mild AR and 40 (2%) patients had moderate/severe AR at the time of hospital discharge. One-year survival (95% confidence interval) was 97.7% (97.1-98.3) in the whole study cohort and without significant difference among the 3 subgroups. One-year cardiac adverse event-free survival (95% confidence interval) was 85.7% (84.2-87.1) and was similar in all 3 study groups in propensity score-weighted analysis. A total of 38 (1.6%) patients required AV reintervention during a 1-year follow-up, without significant difference among subgroups (P = 0.11)., Conclusions: AV repair/AV-sparing root surgery is performed in 5% of patients requiring AV surgery in Germany. Our data demonstrate very satisfactory periprocedural and 1-year survival and cardiac event-free survival after AV repair surgery. Implementation of specific surgical techniques during the index procedure seems to result in comparable outcomes., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Aberrant right subclavian artery is a rare congenital aortic arch anomaly. We report on a case of type A aortic dissection and aberrant right subclavian artery. The 65-year-old female patient received a replacement of the ascending aorta and arch repair using an uncovered AMDS (Ascyrus Medical Dissection Stent; CryoLife Inc., Kennesaw, GA, USA) with debranching of both common carotid arteries. Postoperative computed tomography scan revealed regular aortic blood flow with the unrestricted carotid artery and aberrant right subclavian artery perfusion., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Objectives: The aim of this study was to compare short- and longer-term outcomes of David (DV) versus Florida sleeve (FS) procedure in patients requiring valve-sparing aortic root replacement., Methods: Between January 1996 and December 2020 285 patients received a DV procedure (median age 60 years; 26% females) and 57 patients underwent an FS procedure (median age 64 years; 19% females) in our department. Propensity score matching using patient characteristics led to 58 (DV) versus 57 (FS) patients. End points were defined as primary: freedom from aortic valve and/or aortic root-related reoperation and freedom from aortic regurgitation ≥moderate and secondary: early and late survival., Results: Thirty-day mortality was 2% (DV) and 0% (FS) (P = 0.319). There was 1 early stroke in each group (P = 0.990). Follow-up was complete in 99% with only 1 patient (FS) lost. The 5- and 10-year freedom from aortic valve and/or aortic root related reoperation was 98 ± 2% and 96 ± 3% in the DV group and 92 ± 5% and 84 ± 9% in the FS group, respectively (P = 0.095). The 5- and 10-year freedom from aortic regurgitation ≥moderate was 88 ± 5% and 80 ± 8% in the DV group and 92 ± 5% and 78 ± 1% in the FS group, respectively (P = 0.782). The 5- and 10-year survival rates were 93 ± 4% and 82 ± 6% (DV) vs 75 ± 7% and 67 ± 10% (FS), respectively (P = 0.058). No case of endocarditis (DV) and 3 cases of endocarditis (FS) (P = 0.055) were observed during follow-up., Conclusions: Both DV and FS resulted in similar early and longer-term outcomes with a trend to slightly better performance and survival in the DV group. Florida sleeve procedure might be an alternative approach for patients with higher-risk profiles requiring valve-sparing aortic root replacement., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objectives: There are disparities in the adherence to guideline-recommended therapies after coronary artery bypass graft (CABG). We therefore sought to evaluate the effect of guideline-adherent medical secondary prevention on 1-year outcome after CABG., Methods: Data were taken from the randomized 'Ticagrelor in CABG' trial. From April 2013 until April 2017, patients who underwent CABG were included. For the present analysis, we compared patients who were treated with optimal medical secondary prevention with those where 1 or more of the recommended medications were missing., Results: Follow-up data at 12 months were available in 1807 patients. About half (54%) of them were treated with optimal secondary prevention. All-cause mortality [0.5% vs 3.5%, hazard ratio (HR) 0.14 (0.05-0.37), P < 0.01], cardiovascular mortality [0.1% vs 1.7%, HR 0.06 (0.01-0.46), P = 0.007] and major adverse events [6.5% vs 11.5%, HR 0.54 (0.39-0.74), P < 0.01] were significantly lower in the group with optimal secondary prevention. The multivariable model for the primary end point based on binary concordance to guideline recommended therapy identified 3 independent factors: adherence to guideline recommended therapy [HR 0.55 (0.39-0.78), P < 0.001]; normal renal function [HR 0.99 (0.98-0.99), P = 0.040]; and off-pump surgery [HR 2.06 (1.02-4.18), P = 0.045]., Conclusions: Only every second patient receives optimal secondary prevention after CABG. Guideline adherent secondary prevention therapy is associated with lower mid-term mortality and less adverse cardiovascular events after 12 months., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objectives: The aim of this study was to analyse the outcome of patients between 50 and 69 years of age undergoing biological or mechanical aortic valve replacement., Methods: Data were collected from the German Aortic Valve Registry. Data were analysed regarding baseline characteristics and outcome parameters such as 5-year survival, stroke and reintervention., Results: In total., 3046 patients undergoing isolated surgical aortic valve replacement between 2011 and 2012 were investigated and a propensity score matching was performed. Within this period, 2239 patients received a biological prostheses, while 807 patients received a mechanical prosthesis. Mean age in the biological group was 63.07 (±5.11) and 57.34 (±4.67) in the mechanical group (standardized mean difference 1.172). In the overall cohort, there were more female patients in the biological group (32.7% vs 28.4%) and log EuroSCORE I was higher (5.41% vs 4.26%). After propensity matching (610 pairs), there was no difference in the mortality at 5-year follow-up (12.1% biological vs 9.2% mechanical P = 0.05) nor for reoperation/reintervention (2.5% biological vs 2.0% mechanical, P = 0.546). Patients undergoing mechanical aortic valve replacement suffered from a higher stroke rate 3.3% vs 1.5% (P = 0.04) at 5-year follow-up., Conclusions: Aortic valve replacement with biological or mechanical prostheses showed similar 5-year outcomes for survival and reoperation in a propensity-matched cohort, but significantly increased stroke rate after mechanical aortic valve replacement. This could influence the choice of a mechanical valve in younger patients., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objectives: Myocardial recovery allows for left ventricular assist device (LVAD) explantations after long-term support. Several surgical approaches, including interventional decommissioning, off-pump explantation using a custom-made plug and complete LVAD removal through redo sternotomy, have been described. We present the results from an evaluation of the long-term follow-up of patients who received a titanium sintered plug after LVAD explantation., Methods: We performed a retrospective, European, multicentre analysis of patients who received a titanium sintered plug to seal the apical fixation ring after LVAD explantation. Data were collected from a questionnaire that included demographics, procedural details and follow-up information., Results: Out of 54 contacted centres in 12 countries (n = 179 patients), a total of 68 patients were successfully included in the study. The median follow-up was 34 months (interquartile range: 17-58.5 months); 57 (84%) patients had >1-year follow-up. At the time of the last follow-up, 55 (81%) patients were alive, with a Kaplan-Meier 1-year survival of 90.1% (95% confidence interval: 84.0-98.1%) and a 5-year survival of 80.0% (95% confidence interval: 68.4-92.9%). One patient (1.5%) developed a plug infection originating from an infected part of the incorporated driveline and, after complete removal, is currently in good condition. No postoperative stroke has been reported after plug implantation., Conclusions: In this European multicentre study, the use of a custom-made titanium plug to close the apical fixation ring after LVAD explantation resulted in a low incidence of plug-related complications. With the volume of patients undergoing LVAD explantations after myocardial recovery increasing, the plug has evolved as a simple alternative to more invasive device explantation procedures or decommissioning with a high risk for infection of the remaining system or stroke., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Objectives: To determine the 5-year outcome in patients treated by isolated transcatheter aortic valve implantation (TAVI) or surgical aortic valve replacement (sAVR)-a prospective observational cohort study., Methods: A total of 18 010 patients were included (n = 8942 TAVI and n = 9068 sAVR) in the German Aortic Valve Registry (GARY) who were treated in 2011 and 2012 at 92 sites in central Germany. Eligible patients with TAVI and sAVR were matched using propensity scores in a nearest-neighbour approach. Patients with repeat procedures or unequivocal indication for one treatment option (e.g. frailty) were excluded (n = 4785 for TAVI and n = 2 for sAVR). This led to 13 223 patients (4157 TAVI and 9066 sAVR) as an unmatched subcohort. The main outcome measure was the 5-year all-cause mortality., Results: TAVI patients were significantly older (80.9 ± 6.1 vs 68.5 ± 11.1 years, P < 0.001), had a higher Society of Thoracic Surgeons (STS) score (6.3 ± 4.9 vs 2.6 ± 3.0, P < 0.001) and a higher 5-year all-cause mortality (49.8% vs 16.5%, P < 0.0001). There was no major difference in in-hospital stroke, in-hospital myocardial infarction, or temporary and chronic dialysis. In the propensity score-matched group (n = 3640), there were 763 deaths (41.9%) among 1820 TAVI patients compared with 552 (30.3%) among 1820 treated with sAVR during the 5-year follow-up (hazard ratio 1.51, 95% confidence interval 1.35-1.68; P < 0.0001). New pacemaker implantation was performed in 448 patients (24.6%) after TAVI and in 201 (11.0%) after sAVR (P < 0.0001)., Conclusions: The 5-year follow-up data show that TAVI patients were significantly older and had a higher STS score than sAVR patients. After propensity score matching, TAVI with early-generation prosthesis was associated with significantly higher 5-year all-cause mortality than sAVR., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objectives: Chronic kidney disease (CKD) is a key risk factor in patients undergoing transcatheter aortic valve implantation (TAVI) or surgical aortic valve replacement (SAVR). We analysed the impact of estimated glomerular filtration rate (eGFR) and CKD stages on their mid-term survival., Methods: Data from 29 893 patients enrolled in the German Aortic Valve registry from January 2011 to December 2015 receiving TAVI (n = 12 834) or SAVR (n = 17 059) at 88 sites were included. The impact of renal impairment, as measured by eGFR and CKD stages, was investigated. The primary end-point was 1-year cumulative all-cause mortality., Results: Higher CKD stages were significantly associated to lower in-hospital, 30-day- and 1-year survival rates. Both TAVI- and SAVR-treated patients in CKD 3a, 3b, 4 and 5 stages showed significant and gradually increasing HR values for 1-year all-cause mortality. The same trend persisted in multivariable analysis, although HR values for CKD 3a and 5 did not reach significance in TAVI patients, whereas CKD 4 + 5 did not reach statistical significance in SAVR. Likewise, eGFR as a continuous variable was a significant predictor for 1-year mortality, with the best cut-off points being 47.4 ml/min/1.73 m2 for TAVI and 59.8 ml/min/1.73 m2 for SAVR. Significant 8.6% and 9.0% increases in 1-year mortality were observed for every 5-ml reduction in eGFR for TAVI and SAVR, respectively., Conclusions: CKD ≥3b and CKD ≥3a are the independent major risk factors for mortality in patients undergoing TAVI and SAVR, respectively. In the overall population of patients with severe aortic stenosis, an appropriate stratification based on CKD substage may contribute to a better selection of patients suitable for such therapies., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Aims: Paravalvular leakage (PVL) after transcatheter aortic valve replacement (TAVR) is a common complication in patients with bicuspid aortic valve (BAV). However, predictors and mechanisms of PVL are not well understood in this subset. The aim of this study was to analyse determinants and mechanisms of PVL in BAV and tricuspid aortic valve (TAV)., Methods and Results: Of the 2394 consecutive patients undergoing transfemoral TAVR using new-generation valves at our centre, we identified 242 cases with BAV. To adjust for baseline differences, we performed 3 : 1 propensity score matching (TAVPS  n = 726). We analysed the aortic root anatomy and calcification as well as the number, circumferential distribution, and predilection sites of PVL using pre-procedural multidetector computed tomography and post-TAVR echocardiography. In the matched cohort, the incidence of PVL ≥mild (BAV 51.9% vs. TAVPS 51.7%; P = 0.955) and PVL ≥moderate (BAV 5.0% vs. TAVPS 3.7%; P = 0.393), the circumferential distribution, and independent predictors were similar between BAV and TAVPS. Both the presence of peri-annular calcium chunks or LVOT calcification were highly associated with PVL in BAV and TAVPS patients, whereas in BAV patients neither the presence of a calcium bridge nor the volume of its calcification was related to PVL. Notably, the spatial localization of these lesions did not necessarily match the circumferential leak position., Conclusion: The incidence, circumferential distribution, predilection sites, and predictors of PVL were similar in matched population of BAV and TAVPS patients undergoing transfemoral TAVR using new-generation devices. These novel findings suggest a common underlying mechanism of PVL in both entities., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Comprehensive information on the characteristics of surgical heart valves (SHVs) is essential for optimal valve selection. Such information is also important in assessing SHV function after valve replacement. Despite the existing regulatory framework for SHV sizing and labelling, this information is challenging to obtain in a uniform manner for various SHVs. To ensure that clinicians are adequately informed, the European Association for Cardio-Thoracic Surgery (EACTS), The Society of Thoracic Surgeons (STS) and American Association for Thoracic Surgery (AATS) set up a Task Force comprised of cardiac surgeons, cardiologists, engineers, regulatory bodies, representatives of the International Organization for Standardization and major valve manufacturers. Previously, the EACTS-STS-AATS Valve Labelling Task Force identified the most important problems around SHV sizing and labelling. This Expert Consensus Document formulates recommendations for providing SHV physical dimensions, intended implant position and haemodynamic performance in a transparent, uniform manner. Furthermore, the Task Force advocates for the introduction and use of a standardized chart to assess the probability of prosthesis-patient mismatch and calls valve manufacturers to provide essential information required for SHV choice on standardized Valve Charts, uniformly for all SHV models., (This article has been co-published with permission in the European Journal of Cardio-Thoracic Surgery, The Annals of Thoracic Surgery and The Journal of Thoracic and Cardiovascular Surgery. The 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. © 2020 European Association for Cardio-Thoracic Surgery, The Society of Thoracic Surgeons and American Association for Thoracic Surgery. Published by Oxford University Press.)

Objectives: The purpose of this study was to evaluate the incidence of new pacemaker implantation (NPMI) after surgical aortic valve replacement (SAVR) and transcatheter aortic valve replacement (TAVR), and investigate its influence on 1-year mortality., Methods: Patients who were enrolled in 'The German Aortic Valve Registry' undergoing isolated TAVR or SAVR between 2011 and 2015 were analysed. The rate of NPMI was analysed for both groups and multivariable Cox regression analysis was performed to investigate the possible independent association between NPMI and 1-year mortality., Results: Twenty thousand eight hundred and seventy-two patients who underwent TAVR and 17 750 patients who received SAVR were included in this study. The rate of NPMI was 16.6% after TAVR and 3.6% after SAVR. In the TAVR group, NPMI was associated with significantly increased 1-year mortality in univariable Cox regression analysis [hazard ratio (HR) 1.29, confidence interval (CI) 1.18-1.41; P < 0.001]. This association persisted after adjustment for confounding factors (HR 1.29, CI 1.16-1.43; P < 0.001). In the SAVR group, NPMI significantly increased 1-year mortality in univariable analysis as well (HR 1.55, CI 1.08-2.22; P = 0.02), whereas after multivariable adjustment, NPMI did not emerge as an independent risk factor (HR 1.29, 0.88-1.89; P = 0.19). NPMI was not associated with 30-day mortality in both procedure groups., Conclusions: The rate of NPMI was markedly higher after TAVR compared with SAVR and was independently associated with 1-year mortality after TAVR, whereas this was not significant after SAVR. As 30-day mortality was not different for TAVR and SAVR, the subsequent procedure of an NPMI itself seems not to increase the risk of mortality., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Aims: Peri-procedural transcatheter valve embolization and migration (TVEM) is a rare but potentially devastating complication of transcatheter aortic valve implantation (TAVI). We sought to assess the incidence, causes, and outcome of TVEM in a large multicentre cohort., Methods and Results: We recorded cases of peri-procedural TVEM in patients undergoing TAVI between January 2010 and December 2017 from 26 international sites. Peri-procedural TVEM occurred in 273/29 636 (0.92%) TAVI cases (age 80.8 ± 7.3 years; 53.8% female), of which 217 were to the ascending aorta and 56 to the left ventricle. The use of self-expanding or first-generation prostheses and presence of a bicuspid aortic valve were independent predictors of TVEM. Bail-out measures included repositioning attempts using snares or miscellaneous tools (41.0%), multiple valve implantations (83.2%), and conversion to surgery (19.0%). Using 1:4-propensity matching, we identified a cohort of 235 patients with TVEM (TVEMPS) and 932 patients without TVEM (non-TVEMPS). In the matched cohort, all-cause mortality was higher in TVEMPS than in non-TVEMPS at 30 days (18.6% vs. 4.9%; P < 0.001) and after 1 year (30.5% vs. 16.6%; P < 0.001). Major stroke was more frequent in TVEMPS at 30 days (10.6% vs. 2.8%; P < 0.001), but not at 1 year (4.6% vs. 1.9%; P = 0.17). The need for emergent cardiopulmonary support, major stroke at 30 days, and acute kidney injury Stages 2 and 3 increased the risk of 1-year mortality, whereas a better renal function at baseline was protective., Conclusion: Transcatheter valve embolization and migration occurred in approximately 1% and was associated with increased morbidity and mortality., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Aims: The antiplatelet treatment strategy providing optimal balance between thrombotic and bleeding risks in patients undergoing coronary artery bypass grafting (CABG) is unclear. We prospectively compared the efficacy of ticagrelor and aspirin after CABG., Methods and Results: We randomly assigned in double-blind fashion patients scheduled for CABG to either ticagrelor 90 mg twice daily or 100 mg aspirin (1:1) once daily. The primary outcome was the composite of cardiovascular death, myocardial infarction (MI), repeat revascularization, and stroke 12 months after CABG. The main safety endpoint was based on the Bleeding Academic Research Consortium classification, defined as BARC ≥4 for periprocedural and hospital stay-related bleedings and BARC ≥3 for post-discharge bleedings. The study was prematurely halted after recruitment of 1859 out of 3850 planned patients. Twelve months after CABG, the primary endpoint occurred in 86 out of 931 patients (9.7%) in the ticagrelor group and in 73 out of 928 patients (8.2%) in the aspirin group [hazard ratio 1.19; 95% confidence interval (CI) 0.87-1.62; P = 0.28]. All-cause mortality (ticagrelor 2.5% vs. aspirin 2.6%, hazard ratio 0.96, CI 0.53-1.72; P = 0.89), cardiovascular death (ticagrelor 1.2% vs. aspirin 1.4%, hazard ratio 0.85, CI 0.38-1.89; P = 0.68), MI (ticagrelor 2.1% vs. aspirin 3.4%, hazard ratio 0.63, CI 0.36-1.12, P = 0.12), and stroke (ticagrelor 3.1% vs. 2.6%, hazard ratio 1.21, CI 0.70-2.08; P = 0.49), showed no significant difference between the ticagrelor and aspirin group. The main safety endpoint was also not significantly different (ticagrelor 3.7% vs. aspirin 3.2%, hazard ratio 1.17, CI 0.71-1.92; P = 0.53)., Conclusion: In this prematurely terminated and thus underpowered randomized trial of ticagrelor vs. aspirin in patients after CABG no significant differences in major cardiovascular events or major bleeding could be demonstrated., Clinicaltrials.gov Identifier: NCT01755520., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Intraoperative surgical prosthetic heart valve (SHV) choice is a key determinant of successful surgery and positive postoperative outcomes. Currently, many controversies exist around the sizing and labelling of SHVs rendering the comparison of different valves difficult. To explore solutions, an expert Valve Labelling Task Force was jointly initiated by the European Association for Cardio-Thoracic Surgery (EACTS), The Society of Thoracic Surgeons (STS) and the American Association for Thoracic Surgery (AATS). The EACTS-STS-AATS Valve Labelling Task Force, comprising cardiac surgeons, cardiologists, engineers, regulators and representatives from the International Organization for Standardization (ISO) and major valve manufacturers, held its first in-person meeting in February 2018 in Paris, France. This article was derived from the meeting's discussions. The Task Force identified the following areas for improvement and clarification: reporting of physical dimensions and characteristics of SHVs determining and labelling of SHV size, in vivo and in vitro testing and reporting of SHV haemodynamic performance and thrombogenicity. Furthermore, a thorough understanding of the regulatory background and the role of the applicable ISO standards, together with close cooperation between all stakeholders (including regulatory and standard-setting bodies), is necessary to improve the current situation. Cardiac surgeons should be provided with appropriate information to allow for optimal SHV choice. This first article from the EACTS-STS-AATS Valve Labelling Task Force summarizes the background of SHV sizing and labelling and identifies the most important elements where further standardization is necessary., (This article has been co-published with permission in the European Journal of Cardio-Thoracic Surgery, The Annals of Thoracic Surgery and The Journal of Thoracic and Cardiovascular Surgery. The 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. © 2019 European Association for Cardio-Thoracic Surgery, The Society of Thoracic Surgeons, and The American Association for Thoracic Surgery. Published by Oxford University Press and Elsevier Inc.)

Aims: Transcatheter aortic valve implantation (TAVI) has become the standard treatment for patients with severe aortic valve stenosis at high surgical risk and may be considered for patients with intermediate risk. During the last few years, an increasing number of patients with low surgical risk have been treated with TAVI. In this study, low-risk patients undergoing isolated TAVI or surgical aortic valve replacement (SAVR) were analysed using data from the German Aortic Valve Registry (GARY)., Methods and Results: All patients with a Society of Thoracic Surgeons Score of <4% undergoing TAVI or SAVR in 2014 and 2015 were evaluated. A total of 20 549 low surgical risk patients remained for further analysis, comprising 14 487 surgical patients and 6062 TAVI patients. Since TAVI patients were significantly older and had significantly more co-morbidities, a weighted propensity score model was used to compare SAVR and TAVI patients for in-hospital, 30-day, and 1-year mortality. Transcatheter aortic valve implantation patients showed a significantly higher in-hospital and 30-day survival than SAVR patients (in hospital survival TAVI vs. SAVR: 98.5% vs. 97.3%; P = 0.003; 30-day survival TAVI vs. SAVR: 98.1% vs. 97.1%; P = 0.014). At 1 year, survival rates did not differ significantly (survival TAVI vs. SAVR: 90.0% vs. 91.2%; P = 0.158)., Conclusion: In this first GARY analysis of low-risk patients, weighted comparison showed similar 1-year survival for TAVI and SAVR and higher in-hospital survival for TAVI patients., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2018. For permissions, please email: journals.permissions@oup.com.)

Objectives: We assessed the safety and efficacy of a novel low-profile, 22-Fr transapical delivery system together with the ACURATE neo™ resheathable transcatheter heart valve., Methods: This prospective, single-arm, multicentre study enrolled 60 patients with severe symptomatic aortic stenosis and high surgical risk ineligible for transfemoral access. Primary end points were 6-month mortality and procedural success., Results: The mean age of patients was 79.8 ± 4.7 years, and the patients had severe comorbidities including coronary artery disease (71.7%), diabetes (38.3%), atrial fibrillation (30.0%) and chronic obstructive pulmonary disease (21.7%); logistic EuroSCORE-I, -II and the Society of Thoracic Surgeons (STS) scores were 20.9 ± 8.9%, 6.1 ± 5.0% and 4.3 ± 2.9%, respectively. A non-rib spreading approach using soft tissue retractors only was used in 88.3% of patients (n = 53). Resheathing and repositioning of transcatheter heart valve were performed in 6.7% of cases (n = 4); the device implantation time was 3 ± 2 min. Apical access site complications occurred in 1.7% (n = 1). Procedural success was 98.3% (n = 59), and procedural success in the absence of major adverse cardiac and cerebrovascular events at 30 days was 90.0% (n = 54). At 30 days, cardiovascular and overall mortality were 8.3% (n = 5), stroke rate was 1.7% (n = 1), and 17.2% of patients (n = 10) received a permanent pacemaker implant. No paravalvular leakage ≥2+ was observed, and the mean transvalvular gradient was 5.9 ± 2.7 mmHg. At 6 months, survival was 84.3% with sustained haemodynamic results., Conclusions: This study indicates safety and efficacy of transapical aortic valve implantation using a novel low-profile delivery system. High procedural success, short implantation times and a low rate of apical access site complications underline the favourable safety profile and ease of use., Clinical Trial Registration: ClinicalTrials.gov: NCT02950428.

Objectives: To examine the incidence and timing of new-onset left bundle branch block (LBBB) and new permanent pacemaker implantation (PPI) in patients undergoing transcatheter aortic valve implantation (TAVI) using the repositionable, self-expanding Portico™ TAVI system (St. Jude Medical, St Paul, MN, USA). Clinical impact and periprocedural factors associated with new PPI were also assessed., Methods: A total of 198 high-risk patients without pre-existing pacemaker [83.1 ± 4.7 years, 77.3% women, mean Society of Thoracic Surgeons (STS) 5.8%] from the Pre-CE Mark Portico TAVI system study were prospectively analysed. Twelve-lead electrocardiographic and echocardiographic data were collected prior to, during and after the procedure. Clinical follow-up was performed at 1 year., Results: Transfemoral implantation of the Portico valve was associated with a new PPI rate of 15.2% at 30 days and 16.7% at 1 year. Overall, 53 of the 187 patients without pre-existing LBBB developed new-onset LBBB at 1 year (28.3%); 23 occurred during the procedure. At 30 days, new-onset LBBB spontaneously resolved in 61.0% of patients. New-onset LBBB post-TAVI was not associated with new PPI (P = 0.64); 8 of the 53 patients required new PPI. Multivariable regression analyses revealed pre-existing right bundle branch block (P = 0.004) and aortic annulus diameter (P = 0.001) as independent predictors of new PPI. New PPI at discharge (n = 29) was not associated with increased freedom from all-cause (odds ratio 92.7%, 95% confidence interval 73.7-98.1%; P = 0.49) and cardiovascular (odds ratio 96.6%, 95% confidence interval 77.9-99.5%; P = 0.47) mortality at 1 year., Conclusions: The Portico TAVI system demonstrated an acceptable rate of new PPI at 1 year without increased mortality risk to patients. New-onset LBBB was common during the procedure, with the majority of events spontaneously resolving by 30 days. No intraprocedural factors were shown to independently predict new PPI., Clinical Trial Registration Number: NCT01493284.

Objectives: Due to increasing clinical experience with transcatheter aortic valve implantation (TAVI) procedures, sophisticated imaging and advanced device technology, TAVI complication rates are low; however, patients requiring conversion to surgery are confronted with an increased mortality risk. In this retrospective study, we evaluated the predictors for conversion and the outcomes of these patients., Methods: We analysed the records of all patients undergoing TAVI in our centre from 2011 to 2016 and focused on cases that required conversion to sternotomy. We investigated reasons and risk factors for conversion as well as 30-day and 1-year outcomes., Results: During the study period, 32 (2.1%) of 1775 patients undergoing TAVI required immediate conversion to sternotomy. Annular rupture (5 of 32; 16%), device embolization (9 of 32; 28%) and pericardial tamponade (15 of 32; 47%) were the most common reasons for conversion. Usage of a self-expandable valve showed to be the only predictor for conversion (odds ratio 0.38, 95% confidence interval 0.16-0.90; P = 0.03). Survival at 30 days and 1 year was 56% and 41%, respectively. Patients who survived 30 days after conversion showed higher preoperative ejection fraction, shorter duration of surgery and shorter perfusion time., Conclusions: In this high-volume, single-centre experience, conversion to sternotomy during TAVI occurred in about 2%, with annular rupture, device embolization and pericardial tamponade being the most common causes. Complications requiring conversion showed to be unpredictable. However, in view of these life-threatening complications, the 30-day survival rate exceeding 50% emphasizes the importance of an experienced and well-attuned heart team providing immediate access to surgical bailout procedures.

Renin angiotensin aldosterone system inhibitors/antagonists/blockers (RAASi) are a cornerstone in treatment of patients with cardiovascular diseases especially in those with heart failure (HF) due to their proven effect on surrogate and hard endpoints. Renin angiotensin aldosterone system inhibitors are also the basis in treatment of arterial hypertension, and they are furthermore indicated to reduce events and target organ damage in patients with diabetes and chronic kidney disease, where they have specific indication because of the evidence of benefit. Renin angiotensin aldosterone system inhibitor therapy, however, is associated with an increased risk of hyperkalaemia. Patients with chronic kidney disease and HF are at increased risk of hyperkalaemia and ∼50% of these patients experience two or more yearly recurrences. A substantial proportion of patients receiving RAASi therapy have their therapy down-titrated or more often discontinued even after a single episode of elevated potassium (K+) level. Since RAASi therapy reduces mortality and morbidity in patients with cardiovascular disease steps should, when hyperkalaemia develops, be considered to lower K+ level and enable patients to continue their RAASi therapy. The use of such measures are especially important in those patients with the most to gain from RAASi therapy.

Objectives: Surgical aortic valve replacement (sAVR) is coming under close scrutiny with the recent upswing in the use of less invasive approaches. The aim of this analysis was to identify current trends in patient selection, procedural characteristics and outcomes after sAVR in Germany., Methods: We analysed data from 42 776 patients included in the German Aortic Valve Registry who underwent sAVR with and without coronary artery bypass surgery (CABG) between 2011 and 2015. Baseline, procedural and short-term outcome parameters were analysed., Results: Of all registered patients, 26 618 (62.2%) underwent isolated sAVR and 16 158 (37.8%) sAVR + CABG. The median age was 72 years, and the median Society of Thoracic Surgeons Predicted Risk of Mortality (STS PROM) was 2.3%. From 2011 to 2015, there was a decline in STS PROM (2.4-2.2%, P < 0.001) and a decline in risk factors, such as pulmonary hypertension (9.1-3.2%, P < 0.001), occlusive arterial disease (19.6-17.7%, P = 0.003), mitral regurgitation ≥2° (10.6-7.6%, P < 0.001) and New York Heart Association Class III/IV (65.3-59.2%, P < 0.001). In-hospital mortality was 2.3%, 1.3% had disabling stroke, 0.4% residual aortic regurgitation ≥2°, and the incidence of new-onset pacemaker/implantable cardioverter-defibrillator implantation was 3.9%. There was an increase in the use of biological valves in patients <65 years (50.1-65.7%, P < 0.001), and the proportion of rapid deployment valves increased significantly (1.5-8.4%, P < 0.001) over the investigated time period., Conclusions: Both isolated sAVR as well as sAVR + CABG resulted in excellent in-hospital outcomes based on >42 000 patients treated between 2011 and 2015. The implementation of alternative treatment strategies has resulted in palpable changes in patient and device selection., (© The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Aims: Life-threatening complications occur during transcatheter aortic valve implantation (TAVI) which can require emergent cardiac surgery (ECS). Risks and outcomes of patients needing ECS during or immediately after TAVI are still unclear., Methods and Results: Incidence, risk factors, management, and outcomes of patients requiring ECS during transfemoral (TF)-TAVI were analysed from a contemporary real-world multicentre registry. Between 2013 and 2016, 27 760 patients underwent TF-TAVI in 79 centres. Of these, 212 (0.76%) patients required ECS (age 82.4 ± 6.3 years, 67.5% females, logistic EuroSCORE: 17.1%, STS-score 5.8%). The risk of ECS declined from 2013 (1.07%) to 2014 (0.70%) but remained stable since. Annual TF-TAVI numbers have more than doubled from 2013 to 2016. Leading causes for ECS were left ventricular perforation by the guidewire (28.3%) and annular rupture (21.2%). Immediate procedural mortality (<72 h) of TF-TAVI patients requiring ECS was 34.6%. Overall in-hospital mortality was 46.0%, and highest in case of annular rupture (62%). Independent predictors of in-hospital mortality following ECS were age > 85 years [odds ratio (OR) 1.87, 95% confidence interval (95% CI) (1.02-3.45), P = 0.044], annular rupture [OR 1.96, 95% CI (0.94-4.10), P = 0.060], and immediate ECS [OR 3.12, 95% CI (1.07-9.11), P = 0.037]. One year of survival of the 114 patients surviving the in-hospital period was only 40.4%., Conclusion: Between 2014 and 2016, the need for ECS remained stable around 0.7%. Left ventricular guidewire perforation and annular rupture were the most frequent causes, accounting for almost half of ECS cases. Half of the patients could be salvaged by ECS-nevertheless, 1 year of all-cause mortality was high even in those ECS patients surviving the in-hospital period., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.)

To report on 2 rare cases of balloon-expandable transfemoral transcatheter aortic valve implantation, where a trapped balloon led to complications requiring acute intervention. Both patients were elderly with increased risk profile and had been discussed by the heart team. After standard positioning of the valves using a transfemoral approach, retrieval of the pusher before deployment of the valve was missed. In 1 patient, rapid pacing was continued, the balloon deflated, the pusher pulled back and the balloon repositioned and reinflated. In the other patient, valve migration into the left ventricle occurred. A second valve was deployed. The embolized valve was then recovered from the ventricle via transapical access. Complications can occur in transcatheter aortic valve implantation, even when they are very rare. A predeployment check list, indicating key procedural steps on a standardized basis, should always be followed to easily prevent mishaps., (© The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objectives: Rapid deployment aortic valve replacement (AVR) has been developed to facilitate minimally invasive approaches for cardiac surgery and shorten procedural times. TRITON is a prospectively designed study to assess safety and efficacy of rapid deployment AVR with Edwards INTUITY valve system. This report presents the 5-year outcomes of the TRITON trial., Methods: A total of 295 patients with aortic valve stenosis were enrolled in the TRITON trial and 287 patients received the study valve. Procedural, early (≤30 days) and late (>30 days) outcomes were collected. Valve haemodynamic performance was evaluated at specified time points by an independent Echocardiography Core Laboratory and clinical events adjudicated by an independent Clinical Events Committee., Results: Mean age was 75.3 ± 6.7 years. A total of 158 patients underwent isolated AVR and 129 patients underwent AVR with concomitant procedures. The 5-year survival rates were 85.7 ± 3.4% and 75.2 ± 4.9% for isolated AVR and concomitant AVR, respectively. Overall, freedom from valve-related death at 5 years was 98.2 ± 0.8%. At 5 years, the valve effective orifice area was 1.6 ± 0.3 cm 2 , mean gradient was 10.5 ± 5.4 mmHg and peak gradient was 18.9 ± 9.3 mmHg., Conclusions: The 5-year outcomes of the TRITON trial demonstrate acceptable long-term safety and excellent haemodynamic performance of rapid deployment AVR with the Edwards INTUITY valve system., Clinicaltrials.gov: NCT01445171., (© The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Although sex-specific differences in cardiovascular medicine are well known, the exact influences of sex on the effect of cardiovascular drugs remain unclear. Women and men differ in body composition and physiology (hormonal influences during the menstrual cycle, menopause, and pregnancy) and they present differences in drug pharmacokinetics (absorption, distribution, metabolism, and excretion) and pharmacodynamics, so that is not rare that they may respond differently to cardiovascular drugs. Furthermore, women are also less often treated with evidence-based drugs thereby preventing optimization of therapeutics for women of all ages, experience more relevant adverse drug reactions than men, and remain underrepresented in most clinical trials. Thus, current guidelines for prevention, diagnosis, and medical treatment for cardiovascular diseases are based on trials conducted predominantly in middle-aged men. A better understanding of these sex-related differences is fundamental to improve the safety and efficacy of cardiovascular drugs and for developing proper individualized cardiovascular therapeutic strategies both in men and women. This review briefly summarizes gender differences in the pharmacokinetics and pharmacodynamics of cardiovascular drugs and provides recommendations to close the gaps in our understanding of sex-specific differences in drug efficacy and safety., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For Permissions, please email: journals.permissions@oup.com.)

Objectives: The ACURATE TA TM system is a self-expanding transcatheter heart valve system designed for transapical access which has been proven to be safe and effective in the controlled setting of clinical trials. The SAVI-1 and SAVI-2 registries aimed to assess whether these promising outcomes can be translated into all-comers clinical routine., Methods: From November 2011 to 2012 (SAVI-1), and November 2013 to 2014 (SAVI-2), a total of 500 patients were enrolled in the prospective, all-comers, multicentre, multinational SAVI registries. Patients were treated according to the standard of care at their respective hospitals. We report and compare 30-day and 1-year clinical outcomes between SAVI-1 and -2., Results: Patients were 80.8 ± 6.1 years old, the mean logistic EuroSCORE-I was 23.4 ± 14.3%. Valves were deployed under rapid pacing in 71.3% of the procedures in SAVI-1, and in 3.6% in SAVI-2. There was no relevant difference in clinical and echocardiographic outcomes between SAVI-1 and SAVI-2. Overall mortality at 30 days and 1 year was 6.8% and 19.9%, the stroke rate was 2.2% and 3.7%, respectively; 10.2% of patients had received a permanent pacemaker, and no transcatheter valve-related complications after discharge were observed. Paravalvular leakage ≥2+ was reported in 1.9% of the patients at the early follow-up, and in 2.6% at the 1-year follow-up., Conclusions: The SAVI-registries have confirmed that transapical implantation using the ACURATE TA TM device is safe and effective in an all-comers setting with low complication rates and stable performance outcomes at short-term and 1 year; outcomes were similar between SAVI-1 and -2., (© The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

An aortic aneurysm complicating Kawasaki disease (KD) is extremely rare. We herein report a case of 48-year-old KD patient with severe aortic regurgitation, aneurysm of the aortic root, ascending aorta and aortic arch, and giant heavily calcified coronary aneurysms. The patient underwent successful surgical management. This case raises some unusual technical issues, which are discussed. A review of the literature is also offered., (© The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Tricuspid regurgitation (TR) is the most common lesion of the tricuspid valve (TV). Mild TR is common and usually is benign. However, moderate or severe TR can lead to irreversible myocardial damage and adverse outcomes. Despite these findings, few patients with significant TR undergo surgery. The treatment of functional (secondary) TR in particular remains controversial because of high rates of residual or recurrent TR and poor outcomes following surgical intervention. Traditional teaching that functional TR resolves on its own if the underlying disease is successfully treated has proven to be incorrect. This review aims to clarify management of TR by describing the anatomy, pathophysiology, diagnosis, and treatment of TR, including the eventual possibility of percutaneous TV therapy., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.)

The angiotensin-converting enzyme 2/angiotensin (Ang)-(1-7)/Mas axis of the renin-angiotensin system often opposes the detrimental effects of the angiotensin-converting enzyme/Ang II/Ang II type 1 receptor axis and has been associated with beneficial effects on glucose homeostasis, whereas underlying mechanisms are mostly unknown. Here we investigate the effects of Ang-(1-7) and its receptor Mas on β-cell function. Isolated islets from Mas-deficient and wild-type mice were stimulated with Ang-(1-7) or its antagonists and effects on insulin secretion determined. Islets' cytoplasmic calcium and cAMP concentrations, mRNA amounts of Ins1, Ins2, Pdx1, and Mafa and effects of inhibitors of cAMP downstream signaling were determined. Ang-(1-7) was also applied to mice by osmotic pumps for 14 days and effects on glucose tolerance and insulin secretion were assessed. Ang-(1-7) increased insulin secretion from wild-type islets, whereas antagonists and genetic Mas deficiency led to reduced insulin secretion. The Mas-dependent effects of Ang-(1-7) on insulin secretion did not result from changes in insulin gene expression or changes in the excitation-secretion coupling but from increased intracellular cAMP involving exchange protein activated directly by cAMP. Administration of Ang-(1-7) in vivo had only marginal effects on glucose tolerance in wild-type mice but still resulted in improved insulin secretion from islets isolated of these mice. Interestingly, although less pronounced than in wild types, Ang-(1-7) still affected insulin secretion in Mas-deficient islets. The data indicate a significant function of Ang-(1-7) in the regulation of insulin secretion from mouse islets in vitro and in vivo, mainly, but not exclusively, by Mas-dependent signaling, modulating the accessory pathway of insulin secretion via increase in cAMP.

Aims: Extracorporeal life support (ECLS) has shown encouraging survival rates in patients with in-hospital cardiac arrest; however, its routine use is still controversial. We compared the survival of patients with in-hospital cardiac arrest receiving conventional cardiopulmonary resuscitation (CCPR) to that of patients with ECLS as an adjunct to cardiopulmonary resuscitation (ECPR)., Methods: A total of 353 patients with in-hospital cardiac arrest (272 CCPR and 52 ECPR) were included in this retrospective, propensity score-adjusted (1:1 matched), single-centre study. Primary endpoints were survival at 30 days, long-term survival and neurological outcome defined by the cerebral performance categories score., Results: In the unmatched groups patients undergoing ECPR initially had significantly higher APACHE II scores ( P=0.03), increased norepinephrine dosages ( P=0.03) and elevated levels of creatine kinase ( P<0.0001), creatinine ( P=0.04) and lactate ( P=0.02) before cardiopulmonary resuscitation compared with those undergoing CCPR. After equalising these parameters significant differences were observed in short and long-term survival, favouring ECPR over CCPR (27% vs. 17%; P=0.01 (short-term) and 23.1% vs. 11.5%; P=0.008 (long-term); median follow-up duration after discharge 1136 days (interquartile range 823-1416)). There was no significant difference in the incidence of a cerebral performance categories score of 1 or 2 between the matched groups (CCPR 66.7% vs. ECPR 83.3%; P=0.77). ECLS implantation was the only significant and independent predictor of mortality in multivariate Cox regression analysis (hazard ratio 0.57, 95% confidence interval 0.35-0.90; P=0.02)., Conclusion: In our cohort of cardiovascular patients ECPR was associated with better short- and long-term survival over CCPR, with a good neurological outcome in the majority of the patients with refractory in-hospital cardiac arrest.

Background: Acute kidney injury (AKI) is a complication after major cardiac surgery that is associated with higher rates of morbidity and mortality. MicroRNA-21 (miR-21) has been described as an early biomarker for AKI. We investigated whether miR-21 is predictive of AKI and long-term mortality after cardiac surgery., Methods: Consecutive patients (n = 115) undergoing major cardiac surgery were included. Serum creatinine was measured prior to, 4 h after, and 1, 4 and 7 days after extracorporeal circulation. Diagnosis of post-operative AKI was made in accordance with the international Kidney Disease: Improving Global Outcomes definition of AKI. Serum cystatin C and miR-21 were measured prior to and 4 h after surgery. miR-21 was determined by quantitative RT-PCR and was normalized to miRNA-39 from Caenorhabditis elegans. The median follow-up time was 2.9 years., Results: AKI occurred in 36.5% (n = 42) of all patients. Baseline miR-21 was significantly lower in patients developing cardiac surgery-associated AKI (CSA-AKI) than in patients without CSA-AKI [0.27 (interquartile range, IQR, 0.14-0.30) versus 0.44 (IQR 0.25-0.75); P < 0.01]. Baseline miR-21 predicted CSA-AKI Stage 2/3 with an area under the curve of 0.701 [95% confidence interval (CI) 0.59-0.82; P = 0.007]. Baseline miR-21 <0.31 showed a hazard ratio of 3.11 (95% CI: 1.33-11.26) for CSA-AKI Stage 2/3. Patients with AKI Stage 2/3 had a significantly higher mortality (50 versus 10%; P = 0.0001) and dialysis rate (27 versus 11%; P = 0.038) within the 2.9-year follow-up., Conclusions: Our results indicate that miR-21 has the potential to identify patients at higher risk for CSA-AKI. This predictive value might be helpful in pre-procedural risk assessment and peri-procedural diagnosis and treatment., (© The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Objectives: Several alternative transapical (TA) aortic prostheses for aortic valve implantation (AVI) have recently become available. Data directly comparing the performance of these different TA-AVI valves, however, are sparse. Therefore, we sought to analyse the performance of the better-established balloon-expandable SAPIEN XT™ valve system, and compare it with the recently approved self-expandable ACURATE TA™ system by means of propensity score (PS) analysis., Methods: Samples from a total of 310 consecutive patients treated with transapical transcatheter aortic valve implantation (TAVI) were included (2010-2014). The ACURATE valve was implanted in 40% (n = 131), SAPIEN in 60% (n = 179). To adjust for baseline differences, 1:1 PS matching was used, and resulted in 103 matched pairs. In addition to demographical and clinical variables, potential anatomical confounders (calcification grade: computed tomography (CT) Agatston score; annulus diameter: CT-effective diameter) were included within the PS estimation., Results: For ACURATE- versus SAPIEN-treated patients, the mean age was 83.1 ± 5.4 vs 79.8 ± 9.5 (P < 0.001). Mean Society of Thoracic Surgeon scores were 7.7 ± 4.6 vs 8.1 ± 6.0 (P = 0.56). PS matching resulted in bias reduction <0.2, indicating excellent balance and allowing for valid outcome comparison. Device success, 30-day mortality rate and 1-year survival were comparable. Pacemaker and 30-day neurological event rates were not significantly different. The need for post-ballooning was significantly higher in the self-expandable group (40% vs 9%; P < 0.001). Echocardiography upon discharge demonstrated excellent functional outcomes regarding residual paravalvular leaks (ACURATE: 3% vs SAPIEN: 4%, P = 1.0) with slightly higher mean gradients in the ACURATE group (12 ± 5 mmHg vs 10 ± 5 mmHg, P = 0.003)., Conclusions: The two transapical TAVI devices demonstrated comparable haemodynamic performance and clinical outcome. The self-expandable valve required more frequent post-ballooning without affecting the safety profile., (© The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Cardiovascular disease is the leading cause of morbidity and mortality among patients with diabetes, underscoring the importance of choosing anti-diabetic drugs that do not increase cardiovascular risk but might reduce the risk of cardiovascular events. Most type 2 diabetic patients die from cardiovascular causes despite the beneficial effects of blood pressure (BP) and lipid-lowering medications. The prevalence of patients with cardiovascular disease and diabetes mellitus is growing exponentially. Approximately 40% of patients hospitalized with heart failure and reduced ejection fraction have diabetes mellitus. The recent trials conducted in patients with heart failure who had diabetes showed a different response to standard medication, with these patients being more prone to develop side effects than patients with the same degree of heart failure but without diabetes mellitus. Therefore, careful selection of drug therapy paying particular attention to cardiovascular safety is important in optimizing diabetic therapy. This review discusses the efficacy and safety of the most commonly prescribed anti-diabetic drugs in the context of cardiovascular impact., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.)

Objectives: The novel ACURATE TA™ transcatheter aortic valve (Symetis, Ecublens, Switzerland) is composed of a self-expanding nitinol stent covered by an anti-paravalvular leak skirt designed for transapical implantation. Since Conformite Europeenne (CE)-mark approval, the first 250 patients implanted with the newly approved device have been included in this post-market, multicentre registry., Methods: The registry was conducted at 17 sites in Germany, Italy, Switzerland and Argentina to treat 250 high-risk elderly patients. This all-comers population presented preoperatively with a mean aortic gradient of 43.2 ± 17.4 mmHg, mean age of 80.9 ± 6.3 years, mean society of thoracic surgeons risk score of 8.0 ± 5.9% and mean logistic European System for Cardiac Operative Risk Evaluation (EuroSCORE) I of 22.3 ± 12.7%. The majority of patients (93%) were in New York Heart Association (NYHA) class III/IV. All patients were treated within a multidisciplinary Heart Team., Results: The procedural success rate was 98% (n = 245) with two valve-in-valve procedures and three conversions to conventional surgery. The 30-day mortality rate was 6.8%. Postimplant echocardiography revealed a relevant paravalvular leak (moderate 2+) in 2.3% of patients, with all other patients demonstrating either none/trace or a 1+ leak. The 30-day stroke rate was 2.8% and the mean transvalvular gradient was 12.4 ± 5.8 mmHg. A new pacemaker implantation was required in 10.0% of patients and 85% of patients returning for the follow-up presented in NYHA class I/II., Conclusions: The short-term result of the registry shows a safety and efficacy profile comparable, if not improved in some aspects, with previously approved transcatheter aortic valve implantation devices. These 'real-world' data highlight an excellent functional outcome, especially in regard to a low rate of relevant paravalvular leak., (© The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objectives: Transapical aortic valve implantation (TA-AVI) using the Edwards SAPIEN™ prosthesis has evolved into a routine procedure for selected high-risk elderly patients. The recently introduced SAPIEN™ delivery system (Ascendra II+™) with an added nose cone seems to facilitate direct valve implantation without prior balloon valvuloplasty (BAV). Here, we report our initial experience with this device., Methods: A total of 128 patients were enrolled in the study in 2012 and 2013 and were designated Cohort I. For a subset of 79 patients, exact cardio- computed tomography-based measurements were available; these patients were assigned to Cohort II. All patients received SAPIEN XT™ valves using the TA approach. TA-AVI without pre-ballooning was performed in 31.2% (Cohort I) and 31.6% (Cohort II) of patients. To adjust for baseline variables, propensity score (PS)-based pair matching was used., Results: All valves were implanted successfully. The use of PS matching resulted in bias reduction for both cohorts. For Cohort I, there were no significant differences in the primary end points, which were aortic valve incompetence≥2+, Pmean postimplantation, major stroke, transient ischaemic attack (TIA), requirement for post-dilatation and necessity for new pacemaker implantation. As expected, fluoroscopy time was significantly lower in no-BAV patients. In Cohort II, the 30-day TIA rate was lower in the no-BAV group., Conclusions: Direct TA implantation of the SAPIEN valve without pre-ballooning is feasible, safe, does not seem to compromise functional outcomes and may be associated with fewer neurological events., (© The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objectives: The German Aortic Valve Registry (GARY) seeks to provide information on a real-world, all-comers basis for patients undergoing aortic valve interventions. This registry comprises patients undergoing the complete spectrum of transcutaneous and conventional surgical aortic valve interventions. The aim of this study was to use the GARY registry to evaluate conventional and catheter-based aortic valve interventions in several risk groups., Methods: A total of 13 860 consecutive patients undergoing intervention for aortic valve disease [conventional aortic valve replacement (AVR) or transvascular/transapical TAVR (TV-/TA-TAVR)] were enrolled in 78 German centres in 2011. Baseline, procedural and outcome data, including quality of life, were acquired up to 1 year post-intervention. Vital status at 1 year was known for 98.1% of patients., Results: The 1-year mortality rate was 6.7% for conventional AVR patients (n = 6523) and 11.0% for patients who underwent AVR with coronary artery bypass grafting (n = 3464). The 1-year mortality rate was 20.7 and 28.0% in TV- and TA-TAVR patients, respectively (n = 2695 and 1181). However, if patients were stratified into four risk groups by means of the EuroSCORE and the German AV Score, the highest risk cohorts showed the same mortality at 1 year with either therapy. More than 80% of patients in all groups were in the same or better state of health at 1 year post-intervention and were satisfied with the procedural outcome., Conclusions: Conventional AVR surgery yields excellent results after 1 year in lower-risk patients. Catheter-based AVR is a good alternative in high-risk and elderly patients., (© The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objectives: Precise measurements of aortic annulus dimensions are crucial for prosthesis size selection in patients undergoing transcatheter aortic valve implantation (TAVI). The so-called effective diameter (derived from area) measured in multislice computed tomography (MSCT) images has evolved to be the most precise measurement tool. Usually, the operator must manually adjust the aortic annular plane. Syngo Aortic ValveGuide (Siemens Healthcare) is a new software tool that allows for automatic aortic root reconstruction and annular plane detection. The aim of this study was to compare the effective diameter measured in automatically detected and manually adjusted annular plane., Methods: Seventy-three raw image datasets of preoperative TAVI MSCT scans were analysed using our institutional gold standard (3Mensio Valves™) with manual annular plane adjustment and using Aortic ValveGuide with automatic annular plane detection. The aortic annular circumference was manually marked for both software tools, and the effective diameter was calculated using the formula: effective diameter = 2 × √(circumferential area/π)., Results: Automatic annulus plane detection using Syngo Aortic ValveGuide worked well in all MSCT scans. Minor manual adjustment of the detected plane was necessary in only 3 patients. The mean effective aortic annulus diameter was 23.1 ± 2.4 mm for 3Mensio and 23.3 ± 2.4 mm for Syngo Aortic ValveGuide. Bland-Altman analysis of both imaging software tools showed good agreement (mean difference of 0.16 mm and limits of agreement of -0.48 to 0.80 mm)., Conclusions: Effective aortic annulus diameter measured with Syngo Aortic ValveGuide, as a new imaging software that allows for automatic aortic annular plane detection, shows good agreement to gold standard measurements. Automatic annulus plane detection might reduce the effort for MSCT analysis and may lead to more reproducible aortic annulus measurements. Aortic ValveGuide is part of the DynaCT and in future aortic annulus dimension measurements may be feasible during intraoperatively acquired DynaCT., (© The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: Aortic stenosis is a frequent valvular disease especially in elderly patients. Catheter-based valve implantation has emerged as a valuable treatment approach for these patients being either at very high risk for conventional surgery or even deemed inoperable. The German Aortic Valve Registry (GARY) provides data on conventional and catheter-based aortic procedures on an all-comers basis., Methods and Results: A total of 13 860 consecutive patients undergoing repair for aortic valve disease [conventional surgery and transvascular (TV) or transapical (TA) catheter-based techniques] have been enrolled in this registry during 2011 and baseline, procedural, and outcome data have been acquired. The registry summarizes the results of 6523 conventional aortic valve replacements without (AVR) and 3464 with concomitant coronary bypass surgery (AVR + CABG) as well as 2695 TV AVI and 1181 TA interventions (TA AVI). Patients undergoing catheter-based techniques were significantly older and had higher risk profiles. The stroke rate was low in all groups with 1.3% (AVR), 1.9% (AVR + CABG), 1.7% (TV AVI), and 2.3% (TA AVI). The in-hospital mortality was 2.1% (AVR) and 4.5% (AVR + CABG) for patients undergoing conventional surgery, and 5.1% (TV AVI) and AVI 7.7% (TA AVI)., Conclusion: The in-hospital outcome results of this registry show that conventional surgery yields excellent results in all risk groups and that catheter-based aortic valve replacements is an alternative to conventional surgery in high risk and elderly patients., (© The Author 2013. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Objectives: Assessment of perioperative risk of elderly patients in cardiac surgery is difficult, and most of the common risk scores show over- or underestimation. Two frailty scores, the comprehensive assessment of frailty (CAF) score and the Frailty predicts death One yeaR after CArdiac Surgery Test (FORECAST), were developed as additional tools to estimate the preoperative mortality risk, taking into consideration the frailty status of elderly patients., Methods: Four hundred and fifty patients who were referred for elective cardiac surgery were included. All the patients were assessed with the CAF test and the FORECAST. Thirty-day and 1-year mortality were evaluated by telephone interview. Univariate and bivariate logistic regression were performed to test the predictive power of the tests on mortality. Correlation of the scores with age was calculated with Spearman ranks. Three commensurate groups were built for each of the frailty scores and the outcome was compared between the groups. All analyses were performed for Society of Thoracic Surgeons (STS) and European System for Cardiac Operative Risk Evaluation (EuroSCORE) accordingly., Results: A total of 227 male and 223 female patients were included. Thirty-day mortality was 6.1%, and 1-year mortality was 13.3%. Logistic regression showed that both scores are able to predict 30-day as well as 1-year mortality. Bivariate logistic regression showed that both frailty scores give relevant additional information to the STS and EuroSCORE for the prediction of 1-year mortality. The frailty scores were only weakly correlated with age in contrast to STS and EuroSCORE and therefore can be used as indicator of the biological age of patients besides the numerical age. Survival up to 1 year was relevantly reduced in the group of patients with the higher frailty scores., Conclusions: CAF and FORECAST are additional tools to evaluate elderly patients adequately before elective cardiac surgery, and showed an association with short- and mid-term mortality independently of age.