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Bioprosthetic valve thrombosis may complicate transcatheter aortic valve implantation (TAVI). This meta-analysis sought to evaluate the prevalence and clinical impact of subclinical leaflet thrombosis (SLT) and clinical valve thrombosis (CVT) after TAVI. We summarized diagnostic strategies, prevalence of SLT and/or CVT and estimated their impact on the risk of all-cause death and stroke. Twenty studies with 12,128 patients were included. The prevalence of SLT and CVT was 15.1% and 1.2%, respectively. The risk of all-cause death was not significantly different between patients with SLT (relative risk [RR] 0.77; p = 0.22) and CVT (RR 1.29; p = 0.68) compared with patients without. The risk of stroke was higher in patients with CVT (RR 7.51; p <0.001) as compared with patients without, while patients with SLT showed no significant increase in the risk of stroke (RR 1.81; p = 0.17). Reduced left ventricular function was associated with increased prevalence, while oral anticoagulation was associated with reduced prevalence of bioprosthetic valve thrombosis. Bioprosthetic valve thrombosis is frequent after TAVI, but does not increase the risk of death. Clinical valve thrombosis is associated with a significantly increased risk of stroke. Future studies should focus on prevention and treatment of bioprosthetic valve thrombosis.

We characterized the dynamics of eosinophils in blood and in the infarcted myocardium in patients and in a swine model of reperfused myocardial infarction (MI). The association of eosinophil dynamics with various outcomes was assessed. Serial eosinophil count and pre-discharge cardiac magnetic resonance were carried out in a prospective series of 620 patients with a first ST-elevation MI. In a swine model of reperfused MI, the dynamics of circulating eosinophils and their presence in the infarcted myocardium were determined. In autopsies from chronic MI patients, eosinophils were quantified. Patient eosinophil count sharply decreased 12h post-reperfusion compared to arrival. A lower minimum eosinophil count was associated with more extensive edema, microvascular obstruction, and infarct size as measured by cardiac magnetic resonance, and also with a higher rate of cardiac events (death, re-infarction, or heart failure) during follow-up. In the experimental model, eosinophil count boosted during ischemia and dropped back immediately post-reperfusion. Myocardial samples revealed progressive eosinophil migration into the infarcted myocardium, especially areas with microvascular obstruction. Markers of eosinophil maturation and survival (interleukin-5), degranulation (eosinophil cationic protein) and migration (eotoxin-1) were detected in the blood of patients, and in porcine myocardium. Eosinophil infiltration was detected in autopsies from chronic MI patients. Eosinopenia post-MI was associated with an impaired cardiac structure and adverse events. The decay in circulating eosinophils soon after reperfusion mirrors their migration into the infarcted myocardium, as reflected by their presence in heart samples from swine and patients. Further studies are needed to understanding this unexplored pathway and its therapeutic implications.

Mass, radius and age are three of the most fundamental parameters for celestial objects, enabling insight into the evolution and internal physics of stars, brown dwarfs and planets. Brown dwarfs are hydrogen-rich objects that are unable to sustain core fusion reactions but are supported against collapse by electron degeneracy pressure 1 . As they age, brown dwarfs cool, reducing their radius and luminosity. Young exoplanets follow a similar behaviour. Brown dwarf evolutionary models are relied upon to infer the masses, radii and ages of young brown dwarfs 2 , 3 . Similar models are also used to infer the mass and radius of directly imaged exoplanets 4 . Unfortunately, only sparse empirical mass, radius and age measurements are currently available, and so the models remain mostly unvalidated. Double-line eclipsing binaries provide the most direct route towards the absolute determination of the masses and radii of stars 5 – 7 . Here we report the discovery by SPECULOOS (Search for habitable Planets EClipsing ULtra-cOOl Stars) of the 2M1510A triple system, consisting of a nearby, eclipsing, double-line brown dwarf binary and a widely separated tertiary brown dwarf companion. We find that the system is a member of Argus, a 45 ± 5 million-year-old moving group 8 , 9 . The system’s age matches those of currently known directly imaged exoplanets so 2M1510A provides an opportunity to benchmark evolutionary models of brown dwarfs and young planets. We find that widely used evolutionary models 3 do reproduce the mass, radius and age of the binary components remarkably well, but overestimate their luminosity by up to 0.65 magnitudes, which could result in underestimations of 20% to 35% of photometric masses for directly imaged exoplanets and young-field brown dwarfs. 2M1510 is an approximately 45-million-year-old triple system of brown dwarfs, two of which form a close binary in a 20-day orbit and have almost the same mass (3.82% and 3.75% of the mass of the Sun, respectively). Their physical parameters are in good agreement with evolutionary models except for luminosity, suggesting that we might be underestimating the masses of brown dwarfs and massive exoplanets by about 30%.

Transfemoral Transcatheter Aortic Valve Implantation (TAVI) has become a standard therapy for patients with aortic valve stenosis. Fluoroscopic imaging is essential for TAVI with the anesthesiologist's workplace close to patient's head side. While the use of lead-caps has been shown to be useful for interventional cardiologists, data are lacking for anesthesiologists. A protective cap with a 0.35 lead-equivalent was worn on 15 working days by one anesthesiologist. Six detectors (three outside, three inside) were analyzed to determine the reduction of radiation. Literature search was conducted between April and October 2018. In the observational period, 32 TAVI procedures were conducted. A maximum radiation dose of 0.55 mSv was detected by the dosimeters at the outside of the cap. The dosimeters inside the cap, in contrast, displayed a constant radiation dose of 0.08 mSv. The anesthesiologist's head is exposed to significant radiation during TAVI and it can be protected by wearing a lead-cap.

Background ST-segment elevation myocardial infarction (STEMI) displays circadian variability with the highest incidence in the morning hours. Data on whether the time-of-day at symptom onset affects infarct size or patients’ long-term prognosis are conflicting. We sought to investigate the association of time-of-day at symptom onset with infarct size or long-term mortality in patients with STEMI undergoing primary percutaneous coronary intervention (PPCI). Methods This study included 1206 STEMI patients undergoing PPCI. All patients underwent single photon emission computed tomography (SPECT) imaging with 99mTc-sestamibi before and 7–14 days after PPCI. The co-primary endpoints were final infarct size on day 10 after STEMI and all-cause mortality at 5-year follow-up. Time-of-day at symptom onset of STEMI was categorized in 6-h intervals. Results In patients presenting from 0 to 6 h, 6 to 12 h, 12 to 18 h, and 18 to 24 h, the infarct sizes (median [25th–75th percentiles]) were 10.0 [3.0–24.7], 10.0 [3.0–24.0], 10.0 [3.0–22.0], and 9.0 [3.0–21.0] of the left ventricle, respectively (p = 0.87); the Kaplan–Meier estimates of 5-year all-cause mortality were 13.6%, 8.7%, 13.7% and 9.3%, respectively (log-rank test p = 0.30). After adjustment, time-of-day was not associated with infarct size (p ≥ 0.76 for comparisons with infarct size from reference [6–12 h] time interval) or 5-year all-cause mortality (p ≥ 0.25 for comparisons with mortality from reference [6–12 h] time interval). Time-of-day at symptom onset of STEMI was not associated with differences in the recovery of left ventricular ejection fraction 6 months after STEMI. Conclusions In patients with STEMI undergoing PPCI, time-of-day at symptom onset was neither associated with scintigraphic infarct size, left ventricular ejection fraction recovery at 6 months nor with 5-year mortality.

A higher neprilysin activity has been suggested in women. In this retrospective analysis, we evaluated the association of sex and body mass index (BMI) with soluble neprilysin (sNEP) and recurrent admissions among 1021 consecutive HF outpatients. The primary and secondary endpoints were the number of HF hospitalizations and all-cause mortality, respectively. The association between sNEP with either endpoint was evaluated across sex and BMI categories (≥ 25 kg/m 2 vs. < 25 kg/m 2 ). Bivariate count regression (Poisson) was used, and risk estimates were expressed as incidence rates ratio (IRR). During a median follow-up of 6.65 years (percentile 25%-percentile 75%:2.83–10.25), 702 (68.76%) patients died, and 406 (40%) had at least 1 HF hospitalization. Median values of sNEP and BMI were 0.64 ng/mL (0.39–1.22), and 26.9 kg/m 2 (24.3–30.4), respectively. Left ventricle ejection fraction was < 40% in 78.9% of patients, and 28% were women. In multivariable analysis, sNEP (main effect) was positively associated with HF hospitalizations ( p  = 0.001) but not with mortality ( p  = 0.241). The predictive value of sNEP for HF hospitalizations varied non-linearly across sex and BMI categories ( p -value for interaction = 0.003), with significant and positive effect only on women with BMI ≥ 25 kg/m 2 ( p  = 0.039). For instance, compared to men, women with sNEP of 1.22 ng/mL (percentile 75%) showed a significantly increased risk (IRRs: 1.26; 95% CI: 1.05–1.53). The interaction analysis for mortality did not support a differential prognostic effect for sNEP ( p  = 0.072). In conclusion, higher sNEP levels in overweight women better predicted an increased risk of HF hospitalization.

The benefit of a transcatheter aortic valve replacement (TAVR) can differ in patients, and therapy bears severe risks. High-degree aortic stenosis can lead to cardiac damage such as diffuse myocardial fibrosis, evaluable by extra-cellular volume (ECV) in CMR. Therefore, fibrosis might be a possible risk factor for unfavorable outcome after TAVR. We sought to assess the prognostic value of T1-mapping and ECV to predict adverse events during and after TAVR. The study population consisted of patients undergoing clinically indicated TAVR by performing additional CMR with native and contrast-enhanced T1-mapping sequences for additional evaluation of ECV. Study endpoints were congestive heart failure (CHF) and TAVR-associated conduction abnormalities defined as new onset of left bundle branch block (LBBB), AV-Block or implantation of a pacemaker. 94 patients were examined and followed. Median follow up time was 187 days (IQR 79–357 days). ECV was increased (>30 %) in 38 patients (40 %). There was no significant correlation between ECV and death, Hazard ratio (HR) 0.847 (95 % CI 0.335; 2.14), p = 0.72. ECV in patients with subsequent CHF was higher than in those without an event (33.5 ± 4.6 and 29.1 ± 4.1 %, respectively), but the difference just did not reach the level of significance HR 2.16 (95 % CI 0.969; 4.84), p = 0.06. Patients with post-TAVR conduction abnormality (LBBB, AV-block or pacemaker implantation) had statistically relevant lower ECV values compared to those without an event. Patients with an event had a mean ECV of 28.1 ± 3.16 %; patients without an event had a mean ECV of 29.8 ± 4.53, HR 0.56 (95 % CI 0.32; 0.96), p = 0.036. In this study, elevated myocardial ECV is a predictor of CHF by trend; CMR may be helpful in identifying patients with a high risk for post-TAVR cardiac decompensation benefitting from an intensified post-interventional surveillance. Patients with post-TAVR conductions abnormalities have a significantly decreased ECV. Nevertheless, it remains unclear which precise molecular tissue alteration is the protective factor or risk factor in this case.

Objectives: This study examined the prognostic value of the get-with-the-guidelines heart-failure risk score (GWTG-HF) on mortality in patients with low-flow–low-gradient aortic valve stenosis (LFLG-AS) after transcatheter aortic valve implantation (TAVI). Background: Data on feasibility of TAVI and mortality prediction in the LFLG-AS population are scarce. Clinical risk assessment in this particular population is difficult, and a score has not yet been established for this purpose. Methods: A total of 212 heart failure (HF) patients with real LFLG-AS were enrolled. Patients were classified into low-risk (n = 108), intermediate-risk (n = 90) and high-risk (n = 14) groups calculated by the GWTG-HF score. Clinical outcomes of cardiovascular events according to Valve Academic Research Consortium (VARC-2) recommendations and composite endpoint of death and hospitalization for heart failure (HHF) were assessed at discharge and 1 year of follow-up. Results: Baseline parameters of the groups showed a median age of 81.0 years [77.0; 84.0] (79.0 vs. 82.0 vs. 86.0, respectively p < 0.001), median EuroSCORE II of 6.6 [4.3; 10.7] (5.5 vs. 7.2 vs. 9.1, p = 0.004) and median indexed stroke volume of 26.7 mL/m2 [22.0; 31.0] (28.2 vs. 25.8 vs. 25.0, p = 0.004). The groups significantly differed at follow-up in terms of all-cause mortality (10.2 vs. 21.1 vs. 28.6%; p < 0.035). There was no difference in intrahospital event rate (VARC). Postprocedural mean gradients were lower in high-risk group (7.0 vs. 7.0 vs. 5.0 mmHg, p = 0.011). No differences in postprocedural aortic valve area (1.9 vs. 1.7 vs. 1.9 cm2, p = 0.518) or rate of device failure (5.6 vs. 6.8 vs. 7.7%, p = 0.731) could be observed. After adjustment for known predictors, the GWTG score (HR 1.07 [1.01–1.14], p = 0.030) as well as pacemaker implantation (HR 3.97 [1.34–11.75], p = 0.013) turned out to be possible predictors for mortality. An increase in stroke volume index (SVI) was, in contrast, protective (HR 0.90 [0.83–0.97]; p = 0.006). Conclusions: The GWTG score may predict mortality after TAVI in LFLG-AS HF patients. Interestingly, all groups showed similar intrahospital event and mortality rates, independent of calculated mortality risk. Low SVI and new conduction disturbances associated with PPI after THV implantation had negative impact on mid-term outcome in post-TAVI HF-patients.

Multislice computed tomography (MSCT) has emerged as the mainstay in patients planned for transcatheter aortic valve implantation (TAVI). Incidental findings (IF) in MSCT are common. However, the exact incidence, clinical relevance and further consequences of IF are unclear and it is controversial whether IF adversely affect patients’ outcome. We analyzed MSCT data of 1050 patients screened for TAVI between January 2011 and December 2014. Median follow-up of patients was 20 months. In total, 3194 IF were identified, which were classified into clinically non-relevant IF (2872, 90%) and clinically relevant IF (322, 10%). In 25% of patients (258/1050) at least one clinically relevant IF was present. Age (80 ± 7 vs. 80 ± 7 years; p = 0.198) and EuroSCORE II (3.6% [2.1–5.7] vs. 3.6% [2.1–5.9]; p = 0.874) was similar between patients with and without a clinically relevant IF. TAVI was performed less frequently in patients with a clinically relevant IF (76% vs. 85%; p < 0.001), with more patients receiving surgical aortic valve replacement in that group (14% vs. 11%; p = 0.042), possibly due to the high rate of incidental aneurysms of the ascending aorta (n = 48). If TAVI was performed mortality did not differ (30-days: 4% vs. 3%; p = 0.339, 1-year: 11% vs. 14%; p = 0.226) between patients with and without a clinically relevant IF. Our study is the largest study to analyze prevalence, clinical relevance and therapeutic consequences of IF during screening for TAVI. IF in pre-procedural MSCT are common and clinically relevant in one-quarter of patients. However, these findings had no impact on overall mortality.

Transcatheter aortic valve replacement (TAVR) is the preferred treatment option for older patients with symptomatic severe aortic stenosis. Differences in the properties of available TAVR systems can affect clinical outcomes. Among patients undergoing TAVR, we compared the self-expanding ACURATE neo TAVR system with the balloon-expandable SAPIEN 3 TAVR system with regard to early safety and efficacy. In this randomised non-inferiority trial, patients (aged ≥75 years) undergoing transfemoral TAVR for treatment of symptomatic severe aortic stenosis, and who were deemed to be at increased surgical risk, were recruited at 20 tertiary heart valve centres in Germany, the Netherlands, Switzerland, and the UK. Participants were randomly assigned (1:1) to receive treatment with the ACURATE neo or the SAPIEN 3 with a computer-based randomly permuted block scheme, stratified by study centre and Society of Thoracic Surgeons Predicted Risk of Mortality (STS-PROM) category. The primary composite safety and efficacy endpoint comprised all-cause death, any stroke, life-threatening or disabling bleeding, major vascular complications, coronary artery obstruction requiring intervention, acute kidney injury (stage 2 or 3), rehospitalisation for valve-related symptoms or congestive heart failure, valve-related dysfunction requiring repeat procedure, moderate or severe prosthetic valve regurgitation, or prosthetic valve stenosis within 30 days of the procedure. Endpoint assessors were masked to treatment allocation. Non-inferiority of ACURATE neo compared with SAPIEN 3 was assessed in the intention-to-treat population on the basis of a risk-difference margin of 7·7% for the primary composite endpoint, with a one-sided α of 0·05. This trial is registered with ClinicalTrials.gov (number NCT03011346) and is ongoing but not recruiting. Between Feb 8, 2017, and Feb 2, 2019, up to 5132 patients were screened and 739 (mean age 82·8 years [SD 4·1]; median STS-PROM score 3·5% [IQR 2·6–5·0]) were enrolled. 30-day follow-up was available for 367 (99%) of 372 patients allocated to the ACURATE neo group, and 364 (99%) of 367 allocated to the SAPIEN 3 group. Within 30 days, the primary endpoint occurred in 87 (24%) patients in the ACURATE neo and in 60 (16%) in the SAPIEN 3 group; thus, non-inferiority of the ACURATE neo was not met (absolute risk difference 7·1% [upper 95% confidence limit 12·0%], p=0·42). Secondary analysis of the primary endpoint suggested superiority of the SAPIEN 3 device over the ACURATE neo device (95% CI for risk difference −1·3 to −12·9, p=0·0156). The ACURATE neo and SAPIEN 3 groups did not differ in incidence of all-cause death (nine patients [2%] vs three [1%]) and stroke (seven [2%] vs 11 [3%]); whereas acute kidney injury (11 [3%] vs three [1%]) and moderate or severe prosthetic aortic regurgitation (34 [9%] vs ten [3%]) were more common in the ACURATE neo group. TAVR with the self-expanding ACURATE neo did not meet non-inferiority compared to the balloon-expandable SAPIEN 3 device in terms of early safety and clinical efficacy outcomes. An early composite safety and efficacy endpoint was useful in discriminating the performance of different TAVR systems. Boston Scientific (USA).