Transcatheter or Surgical Treatment of Aortic-Valve Stenosis.

BACKGROUND: Among low-risk patients with severe, symptomatic aortic stenosis who are eligible for both transcatheter aortic-valve implantation (TAVI) and surgical aortic-valve replacement (SAVR), data are lacking on the appropriate treatment strategy in routine clinical practice. METHODS: In this randomized noninferiority trial conducted at 38 sites in Germany, we assigned patients with severe aortic stenosis who were at low or intermediate surgical risk to undergo either TAVI or SAVR. Percutaneous- and surgical-valve prostheses were selected according to operator discretion. The primary outcome was a composite of death from any cause or fatal or nonfatal stroke at 1 year. RESULTS: A total of 1414 patients underwent randomization (701 to the TAVI group and 713 to the SAVR group). The mean (±SD) age of the patients was 74±4 years; 57% were men, and the median Society of Thoracic Surgeons risk score was 1.8% (low surgical risk). The Kaplan-Meier estimate of the primary outcome at 1 year was 5.4% in the TAVI group and 10.0% in the SAVR group (hazard ratio for death or stroke, 0.53; 95% confidence interval [CI], 0.35 to 0.79; P<0.001 for noninferiority). The incidence of death from any cause was 2.6% in the TAVI group and 6.2% in the SAVR group (hazard ratio, 0.43; 95% CI, 0.24 to 0.73); the incidence of stroke was 2.9% and 4.7%, respectively (hazard ratio, 0.61; 95% CI, 0.35 to 1.06). Procedural complications occurred in 1.5% and 1.0% of patients in the TAVI and SAVR groups, respectively. CONCLUSIONS: Among patients with severe aortic stenosis at low or intermediate surgical risk, TAVI was noninferior to SAVR with respect to death from any cause or stroke at 1 year. (Funded by the German Center for Cardiovascular Research and the German Heart Foundation; DEDICATE-DZHK6 ClinicalTrials.gov number, NCT03112980.).

Improved integration of single-cell transcriptome data demonstrates common and unique signatures of heart failure in mice and humans.

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.

Non-femoral focused transaxillary access in TAVI: GARY data analysis and future trends.

BACKGROUND: In patients not suitable for transfemoral transcatheter aortic valve implantation (TAVI), several access strategies can be chosen. AIM: To evaluate the use and patient outcomes of transaxillary (TAx), transapical (TA), and transaortic (TAo) as alternative access for TAVI in Germany; to further evaluate surgical cutdown vs. percutaneous TAx access. METHODS: All patients entered the German Aortic Valve Registry (GARY) between 2011 and 2019 who underwent non-transfemoral TAVI were included in this analysis. Patients with TA, TAo, or TAx TAVI were compared using a weighted propensity score model. Furthermore, a subgroup analysis was performed for TAx regarding the percutaneous or surgical cutdown approach. RESULTS: Overall, 9686 patients received a non-transfemoral access. A total of 8918 patients (92.1%) underwent TA, 398 (4.1%) TAo, and 370 (3.8%) TAx approaches. Within the TAx subgroup, 141 patients (38.1%) received subclavian cutdown, while 200 (54.1%) underwent a percutaneous approach. The TA patients had a significantly lower 30-day survival than TAx patients (TA 90.92% vs. TAx 95.59%, p = 0.006; TAo 92.22% vs. TAx 95.59%, p = 0.102). Comparing percutaneous and cutdown TAx approaches, no significant differences were seen. However, more vascular complications occurred (TA 1.8%, TAo 2.4%, TAx 12.2%; p < .001), and the hospital length of stay was shorter (TA 12.9 days, TAo 14.1 days, TAx 12 days; p < .001) after TAx access. CONCLUSION: It may be reasonable to consider TAx access first in patients not suitable for TF-TAVI, because the 30-day survival was higher compared with TA access and the 1-year survival was higher compared with TAo access. It remains important for the heart teams to offer alternative access modalities for patients not amenable to the standard TF-TAVI approaches.

Comparison of two self-expanding transcatheter heart valves for degenerated surgical bioprostheses: the AVENGER multicentre registry.

BACKGROUND: There is a lack of comparative data on transcatheter aortic valve implantation (TAVI) in degenerated surgical prostheses (valve-in-valve [ViV]). AIMS: We sought to compare outcomes of using two self-expanding transcatheter heart valve (THV) systems for ViV. METHODS: In this retrospective multicentre registry, we included consecutive patients undergoing transfemoral ViV using either the ACURATE neo/neo2 (ACURATE group) or the Evolut R/PRO/PRO+ (EVOLUT group). The primary outcome measure was technical success according to Valve Academic Research Consortium (VARC)-3. Secondary outcomes were 30-day all-cause mortality, device success (VARC-3), coronary obstruction (CO) requiring intervention, rates of severe prosthesis-patient mismatch (PPM), and aortic regurgitation (AR) ≥moderate. Comparisons were made after 1:1 propensity score matching. RESULTS: The study cohort comprised 835 patients from 20 centres (ACURATE n=251; EVOLUT n=584). In the matched cohort (n=468), technical success (ACURATE 92.7% vs EVOLUT 88.9%; p=0.20) and device success (69.7% vs 73.9%; p=0.36) as well as 30-day mortality (2.8% vs 1.6%; p=0.392) were similar between the two groups. The mean gradients and rates of severe PPM, AR ≥moderate, or CO did not differ between the groups. Technical and device success were higher for the ACURATE platform among patients with a true inner diameter (ID) >19 mm, whereas a true ID ≤19 mm was associated with higher device success - but not technical success - among Evolut recipients. CONCLUSIONS: ViV TAVI using either ACURATE or Evolut THVs showed similar procedural outcomes. However, a true ID >19 mm was associated with higher device success among ACURATE recipients, whereas in patients with a true ID ≤19 mm, device success was higher when using Evolut.

Personalised preinterventional risk stratification of mortality, length of stay and hospitalisation costs in transcatheter aortic valve implantation using a machine learning algorithm: a pilot trial.

INTRODUCTION: Risk stratification based on Euroscore II (ESII) is used in some centres to assist decisions to perform transcatheter aortic valve implant (TAVI) procedures. ESII is a generic, non-TAVI-specific metric, and its performance fades for mortality at follow-up longer than 30 days. We investigated if a TAVI-specific predictive model could achieve improved predictive preinterventional accuracy of 1-year mortality compared with ESII. PATIENTS AND METHODS: In this prospective pilot study, 284 participants with severe symptomatic aortic valve stenosis who underwent TAVI were enrolled. Standard clinical metrics (American Society of Anesthesiology (ASA), New York Heart Association and ESII) and patient-reported outcome measures (EuroQol-5 Dimension-Visual Analogue Scale, Kansas City Cardiomyopathy Questionnaire and Clinical Frailty Scale (CFS)) were assessed 1 day before TAVI. Using these data, we tested predictive models (logistic regression and decision tree algorithm (DTA)) with 1-year mortality as the dependent variable. RESULTS: Logistic regression yielded the best prediction, with ASA and CFS as the strongest predictors of 1-year mortality. Our logistic regression model score showed significantly better prediction accuracy than ESII (area under the curve=0.659 vs 0.800; p=0.002). By translating our results to a DTA, cut-off score values regarding 1-year mortality risk emerged for low, intermediate and high risk. Treatment costs and length of stay (LoS) significantly increased in high-risk patients. CONCLUSIONS AND SIGNIFICANCE: A novel TAVI-specific model predicts 1-year mortality, LoS and costs after TAVI using simple, established, transparent and inexpensive metrics before implantation. Based on this preliminary evidence, TAVI team members and patients can make informed decisions based on a few key metrics. Validation of this score in larger patient cohorts is needed.

Towards quantification of doping in gallium arsenide nanostructures by low-energy scanning electron microscopy and conductive atomic force microscopy.

We calculate a universal shift in work function of 59.4 meV per decade of dopant concentration change that applies to all doped semiconductors and from this use Monte Carlo simulations to simulate the resulting change in secondary electron yield for doped GaAs. We then compare experimental images of doped GaAs layers from scanning electron microscopy and conductive atomic force microscopy. Kelvin probe force microscopy allows to directly measure and map local work function changes, but values measured are often smaller, typically only around half, of what theory predicts for perfectly clean surfaces.

Comparison of contemporary transcatheter heart valve prostheses: data from the German Aortic Valve Registry (GARY).

BACKGROUND: Various second-generation transcatheter heart valve (THV) prostheses with high clinical efficacy and safety are available, but there is limited large-scale data available comparing their hemodynamic performance and clinical implications. OBJECTIVE: To compare the hemodynamic performance and short-term clinical outcome of four second-generation THV prostheses. METHODS: 24,124 patients out of the German Aortic Valve Registry who underwent transfemoral transcatheter aortic valve implantation (TAVI) (Evolut™ R n = 7028, Acurate neo™ n = 2922, Portico n = 878 and Sapien 3 n = 13,296) were included in this analysis. Propensity-score weighted analysis was performed to control for differences in age, left ventricular function, STS score and sex. Primary endpoint was survival at one-year, secondary endpoints were 30 days survival, pre-discharge transvalvular gradients, paravalvular leakage and peri-procedural complications. RESULTS: Thirty-day and one-year survival were not significantly different between the four patient groups. Transvalvular gradients in Evolut™ R and Acurate neo™ were significantly lower as compared to Portico and Sapien 3 at hospital discharge. This difference exists across all annulus sizes. Paravalvular leakage ≥ II occurred significantly less often in the Sapien 3 group (1.2%, p < 0.0001). Rate of severe procedural complications was low and comparable in all groups. Permanent pacemaker implantation rate at one year was lowest in the ACUARATE neo group (13.0%) and highest in the Evolut™ R group (21.9%). CONCLUSION: Albeit comparable short-term clinical outcomes there are certain differences regarding hemodynamic performance and permanent pacemaker implantation rate between currently available THV prostheses which should be considered for individual prosthesis selection.

Aortic Valve Repair Results in Better 1-Year Survival Than Replacement: Results From German Aortic Valve Registry.

BACKGROUND: Aortic valve (AV) repair is an evolving surgical strategy in the treatment of nonelderly adults with aortic regurgitation. We aimed to determine the 1-year outcome after AV repair vs surgical AV replacement (sAVR) using real-world data from the German Aortic Valve Registry. METHODS: A total of 8076 aortic regurgitation patients (mean age, 59.1 ± 15.0 years; 76% men; mean The Society of Thoracic Surgeons score, 1.3 ± 1.1), who underwent AV surgical procedures between 2011 and 2015, were identified from German Aortic Valve Registry. The AV was repaired in 2327 patients (29%), and the remaining 5749 patients (71%) underwent sAVR. A weighted propensity score model, including the variables of age, sex, and The Society of Thoracic Surgeons score, was used to correct for baseline differences between AV repair and sAVR cohorts. The primary end point was 1-year survival after AV repair vs sAVR. Secondary end points were freedom from cardiac events and AV reinterventions. RESULTS: Survival at 1 year was 97.7% (95% CI, 97.0%-98.5%) in the AV repair cohort vs 96.4% (95% CI, 95.9%-96.9%) in the propensity score-weighted sAVR cohort (log-rank P < .001). Cox regression revealed a significant advantage of AV repair vs sAVR (hazard ratio, 0.68; 95% CI, 0.51-0.90; P < .0001) on 1-year survival, which was independent of age. Cardiac event-free survival at 1 year was 85.7% (95% CI, 483.8%-87.7%) in the AV repair group vs 81.7% (95% CI, 80.7%-82.9%) in the sAVR group (log-rank P < .001). AV reintervention was required in 38 AV repair patients (1.6%) compared with 1.6% in the sAVR cohort (P = .59). CONCLUSIONS: AV repair surgery, whenever intraoperatively feasible, is associated with a significantly better 1-year survival and 1-year cardiac event-free survival compared with sAVR.

Trilateral versus Bilateral Antegrade Cerebral Perfusion in Frozen Elephant Trunk: A Propensity Score Analysis.

OBJECTIVE: Spinal cord injury (SCI) with subsequent paraplegia and/or stroke after arch repair with frozen elephant trunk (FET) remain the most devastating complications. In this study, we aim to examine the impact of different cerebral perfusion strategies on the neurological outcome comparing bilateral antegrade cerebral perfusion (bACP) and trilateral antegrade cerebral perfusion (tACP). METHODS: Between 2009 and 2021, 88 patients underwent total arch replacement using a hybrid prosthesis in FET technique for acute (40.4%) and chronic (59.6%) aortic pathologies. After excluding 14 patients who underwent FET with unilateral ACP the remaining 74 patients were divided into two groups. Propensity score matching was performed based on pre- and perioperative patient characteristics resulting in 22 patients in each group. The primary endpoint was a combination of major cerebral event and SCI. Secondary end point was all-cause mortality. RESULTS: Major cerebral events occurred in 9% of the patients in bACP versus 13.6% in tACP group (p = 0.63). No postoperative SCI was observed in patients with bACP and only one patient suffered SCI with tACP (p = 0.31). There was no significant difference in 30-day mortality between the two groups (22.7% in bACP vs. 13.6% in tACP; p = 0.43). CONCLUSION: In patients undergoing total aortic arch repair using FET technique, both perfusion strategies (bilateral and trilateral ACP) are safe and effective. The rates of neurological complications as well as mortalities are acceptably low in both groups. Further studies with larger patient cohorts are warranted.

The evolution of indium precipitation in gallium focused ion beam prepared samples of InGaAs/InAlAs quantum wells under electron beam irradiation.

Gallium ion (Ga+ ) beam damage induced indium (In) precipitation in indium gallium arsenide (InGaAs)/indium aluminium arsenide (InAlAs) multiple quantum wells and its corresponding evolution under electron beam irradiation was investigated by valence electron energy loss spectroscopy (VEELS) and high-angle annular dark-field imaging (HAADF) in scanning transmission electron microscopy (STEM). Compared with argon ion milling for sample preparation, the heavier projectiles of Ga+ ions pose a risk to trigger In formation in the form of tiny metallic In clusters. These are shown to be sensitive to electron irradiation and can increase in number and size under the electron beam, deteriorating the structure. Our finding reveals the potential risk of formation of In clusters during focused ion beam (FIB) preparation of InGaAs/InAlAs quantum well samples and their subsequent growth under STEM-HAADF imaging, where initially invisible In clusters of a few atoms can move and swell during electron beam exposure.

Correction: Hlavicka et al. Long-Term Outcomes after Aortic Valve and Root Replacement in a Very High-Risk Population. J. Cardiovasc. Dev. Dis. 2022, 9, 197.

The authors would like to make the following corrections to the published paper [...].

Next-generation feedstocks methanol and ethylene glycol and their potential in industrial biotechnology.

Microbial fermentation processes are expected to play an important role in reducing dependence on fossil-based raw materials for the production of everyday chemicals. In order to meet the growing demand for biotechnological products in the future, alternative carbon sources that do not compete with human nutrition must be exploited. The chemical conversion of the industrially emitted greenhouse gas CO2 into microbially utilizable platform chemicals such as methanol represents a sustainable strategy for the utilization of an abundant carbon source and has attracted enormous scientific interest in recent years. A relatively new approach is the microbial synthesis of products from the C2-compound ethylene glycol, which can also be synthesized from CO2 and non-edible biomass and, in addition, can be recovered from plastic waste. Here we summarize the main chemical routes for the synthesis of methanol and ethylene glycol from sustainable resources and give an overview of recent metabolic engineering work for establishing natural and synthetic microbial assimilation pathways. The different metabolic routes for C1 and C2 alcohol-dependent bioconversions were compared in terms of their theoretical maximum yields and their oxygen requirements for a wide range of value-added products. Assessment of the process engineering challenges for methanol and ethylene glycol-based fermentations underscores the theoretical advantages of new synthetic metabolic routes and advocates greater consideration of ethylene glycol, a C2 substrate that has received comparatively little attention to date.

Transcatheter aortic valve implantation versus surgical aortic valve replacement in patients at low to intermediate surgical risk: rationale and design of the randomised DEDICATE Trial.

Transcatheter aortic valve implantation (TAVI) has become the preferred treatment option for patients with severe aortic stenosis at increased risk for surgical aortic valve replacement (SAVR) and for older patients irrespective of risk. However, in younger, low-risk patients for whom both therapeutic options, TAVI and SAVR, are applicable, the optimal treatment strategy remains controversial, as data on long-term outcomes remain limited. The DEDICATE-DZHK6 Trial is an investigator-initiated, industry-independent, prospective, multicentre, randomised controlled trial investigating the efficacy and safety of TAVI compared to SAVR in low- to intermediate-risk patients aged 65 years or older. To evaluate both treatment strategies, approximately 1,404 patients determined eligible for both TAVI and SAVR by the interdisciplinary Heart Team were randomised to TAVI or SAVR. Broad inclusion and strict exclusion criteria targeted an all-comers patient population. Procedures were performed according to local best practice with contemporary routine medical devices. The primary endpoints are a composite of mortality or stroke at 1 year and 5 years in order to incorporate midterm efficacy results and complement early safety data. Primary outcomes will be tested sequentially for non-inferiority and superiority. The DEDICATE-DZHK6 Trial has been designed to mirror clinical reality for the treatment of severe aortic stenosis and provide unique information on overall outcomes after TAVI and SAVR that can be directly applied to clinical routines. Its results will help further define optimal treatment strategies for low- to intermediate-risk patients in whom both TAVI and SAVR are currently advisable.

Chemical Structure Comparison via Scanning Electron Microscopy of Spent Commercial Nickel-Metal Hydride Batteries.

Back-scattered electron imaging and X-ray elemental mapping were combined in a tabletop scanning electron microscope (SEM) to investigate cross-sections of three AA-type (mignon) nickel-metal hydride (NiMH) batteries from different manufacturers. All batteries underwent 500-800 charge/discharge cycles and reached their end of lifetime after several years as they could no longer hold any significant electric charge (less than 20% of nominal charge capacity), but none showed any short-circuiting. The types of degradation observed in this field study included electrode swelling, metallic nickel formation and carbon incorporation into pores in the positive electrodes and, in the negative electrodes, metal alloy segregation of different elements such as nickel, lanthanum and, in one case, sodium, as well as grain break-up and pore formation. All these phenomena could readily be observed at rather small magnifications. This will be important for the improvement of NiMH batteries, for which new generations with nominally slightly increased charge capacities are being marketed all the time.

Outcomes After Transcatheter Mitral Valve Replacement According to Regurgitation Etiology.

BACKGROUND: Whether transcatheter mitral valve replacement (TMVR) devices perform similarly with respect to the underlying mitral regurgitation (MR) etiology remains unknown. The aim of the present analysis was to assess outcomes of TMVR according to the MR underlying etiology among the CHoice of OptImal transCatheter trEatment for Mitral Insufficiency (CHOICE-MI) registry. METHODS: Of 746 patients, 229 patients (30.7%) underwent TMVR. The study population was subdivided according to primary, secondary, or mixed MR. Patients with mitral annular calcification were excluded. The primary study endpoint was a composite endpoint of all-cause mortality or hospitalization for heart failure at 1 year. Secondary study endpoints were all-cause and cardiovascular mortality at 1 year, New York Heart Association functional class, and residual MR, both at discharge and 1 year. RESULTS: The predominant MR etiology was secondary MR (58.4%), followed by primary MR (28.7%) and mixed MR (12.9%). Technical success and procedural mortality were similar according to MR etiology. Discharge echocardiography revealed residual MR 2+ in 11.3%, 3.7%, and 5.3% of patients with primary, secondary, and mixed MR, respectively (P = .1). MR elimination was similar in all groups up to the 1-year follow-up. There was no difference in terms of primary combined outcome occurrence according to MR etiology. One-year all-cause mortality was reported in 28.8%, 24.2%, and 32.1% of patients with primary, secondary, and mixed MR, respectively (P = .07). CONCLUSIONS: In our study we did not find differences in short-term and 1-year outcomes after TMVR according to MR etiology.

Single-nuclear transcriptome profiling identifies persistent fibroblast activation in hypertrophic and failing human hearts of patients with longstanding disease.

AIMS: Cardiac fibrosis drives the progression of heart failure in ischaemic and hypertrophic cardiomyopathy. Therefore, the development of specific anti-fibrotic treatment regimens to counteract cardiac fibrosis is of high clinical relevance. Hence, this study examined the presence of persistent fibroblast activation during longstanding human heart disease at a single-cell resolution to identify putative therapeutic targets to counteract pathological cardiac fibrosis in patients. METHODS AND RESULTS: We used single-nuclei RNA sequencing with human tissues from two samples of one healthy donor, and five hypertrophic and two failing hearts. Unsupervised sub-clustering of 7110 nuclei led to the identification of 7 distinct fibroblast clusters. De-convolution of cardiac fibroblast heterogeneity revealed a distinct population of human cardiac fibroblasts with a molecular signature of persistent fibroblast activation and a transcriptional switch towards a pro-fibrotic extra-cellular matrix composition in patients with established cardiac hypertrophy and heart failure. This sub-cluster was characterized by high expression of POSTN, RUNX1, CILP, and a target gene adipocyte enhancer-binding protein 1 (AEBP1) (all P < 0.001). Strikingly, elevated circulating AEBP1 blood level were also detected in a validation cohort of patients with confirmed cardiac fibrosis and hypertrophic cardiomyopathy by cardiac magnetic resonance imaging (P < 0.01). Since endogenous AEBP1 expression was increased in patients with established cardiac hypertrophy and heart failure, we assessed the functional consequence of siRNA-mediated AEBP1 silencing in human cardiac fibroblasts. Indeed, AEBP1 silencing reduced proliferation, migration, and fibroblast contractile capacity and α-SMA gene expression, which is a hallmark of fibroblast activation (all P < 0.05). Mechanistically, the anti-fibrotic effects of AEBP1 silencing were linked to transforming growth factor-beta pathway modulation. CONCLUSION: Together, this study identifies persistent fibroblast activation in patients with longstanding heart disease, which might be detected by circulating AEBP1 and therapeutically modulated by its targeted silencing in human cardiac fibroblasts.