IPPMed (Germany)

Although women with severe symptomatic aortic stenosis have more complications than men when undergoing surgical valve replacement, they are under-represented in clinical trials. The Randomized researcH in womEn all comers wIth Aortic stenosis (RHEIA) trial investigates the balance of benefits and risks of transcatheter aortic valve implantation (TAVI) vs. surgery in women. Women were randomized 1:1 to transfemoral TAVI with a balloon-expandable valve or surgery. The primary composite endpoint was death, stroke, or (valve, procedure or heart failure related) rehospitalization at 1 year. Non-inferiority testing with a pre-specified 6% margin and superiority testing were performed in the as-treated population. At 48 European centres, 443 women underwent randomization, and 420 were treated as randomized. Mean age was 73 years, and the mean estimated surgical risk of death was 2.1% (Society of Thoracic Surgeons risk score). Kaplan-Meier estimates of the primary endpoint event rates at 1 year were 8.9% in the TAVI and 15.6% in the surgery group. This difference of -6.8% with an upper 95% confidence limit of -1.5% demonstrated the non-inferiority of TAVI (P < .001). The two-sided 95% confidence interval of -13.0% to -.5% further resulted in superiority (P = .034). The 1-year incidence of the primary endpoint components was: .9% with TAVI vs. 2.0% with surgery for death from any cause, 3.3% vs. 3.0% for stroke, and 5.8% vs. 11.4% for rehospitalization. Among women with severe aortic stenosis, the incidence of the composite of death, stroke, or rehospitalization at 1 year was lower with TAVI than with surgery. NCT04160130.

ABSTRACTBackgroundRandomized clinical trials demonstrated similar efficacy and improved safety of direct oral anticoagulants versus warfarin in patients with atrial fibrillation (AF). Long‐term data in routine clinical practice are needed.HypothesisPatients with AF receiving edoxaban at baseline continue to have low annualized effectiveness and safety event rates in the second year of follow‐up, with regional variations observed.MethodsThe Global ETNA‐AF program is a prospective, noninterventional study of patients with AF receiving edoxaban. Patient characteristics and annualized clinical event rates were assessed overall and by region across the 2‐year follow‐up. Annualized event rates of bleeding and thromboembolic events were assessed within the first year and conditionally in patients who were event‐free up to 12 months in the second year.ResultsThis analysis comprised 26 805 patients from Europe (n = 13 164), Japan (n = 10 342), and non‐Japanese Asian regions (n = 3299). Patients from Europe had the highest burden of comorbidities. The annualized event rates for major bleeding, any stroke, all‐cause death, and cardiovascular death varied by region. The global annualized event rates in the first and second year were 1.31%/year and 0.86%/year for major bleeding, 1.06%/year and 0.65%/year for any stroke, 0.84%/year and 0.73%/year for cardiovascular death, and 3.05%/year and 3.18%/year for all‐cause death.ConclusionAnnualized event rates for any stroke and major bleeding remained low through 2‐year follow‐up for patients with AF receiving edoxaban at baseline. Differences in annualized event rates for all‐cause and cardiovascular mortality between Europe, Japan, and non‐Japanese Asian regions may reflect variations in baseline characteristics.Trial RegistrationEurope, NCT02944019; Japan, UMIN000017011; Korea/Taiwan, NCT02951039; Hong Kong, NCT03247582; and Thailand, NCT03247569.

Arrhythmia recurrence after pulmonary vein isolation (PVI) is common. We conducted a multicenter, randomized trial to determine the impact of increased physical activity on atrial fibrillation recurrence after PVI. From 2018 to 2020, we randomly assigned 200 patients with atrial fibrillation to the ACTION or NO-ACTION group in 4 different centers in the local country of Brandenburg, Germany. Patients were eligible if they were scheduled to undergo PVI, aged ≥50 to ≤77 years, body mass index ≥23 to ≤35 kg/m2, and accepted wearing an activity tracker allowing 24-hour activity monitoring via mobile app. Patients in the ACTION group were actively remote-controlled via transmitted activity data by a physiotherapist, and individual motivational interviewing call sessions were scheduled with each ACTION patient every 2 weeks. The primary end point was the composite of recurrence of any atrial arrhythmia >30 seconds, additional ablation procedure, cardioversion, and new onset of antiarrhythmic drugs earliest after 90 days after index PVI over 12 months. Overall, the median age of patients was 66 (interquartile range, 61-71) years, 33.5% were women, and 52% had persistent atrial fibrillation. The number of steps per day increased in both groups of patients from baseline to 12 months (P<0.001). The absolute increase in steps per day did not differ between patients in the ACTION group with +3205 steps (597-4944) compared with those in the NO-ACTION group +2423 steps (17-4284), P=0.325. Unadjusted intention-to-treat analysis showed no difference in the primary composite end point in the ACTION group (27.3%) versus the NO-ACTION group (32.7%), P=0.405. Physical activity improved in patients after PVI. The present randomized controlled trial shows that activity tracker and motivational calls to increase physical activity versus activity tracker alone did not reduce the occurrence of the primary composite end point of atrial fibrillation recurrence or the absolute increase in steps per day. URL: https://www.cochranelibrary.com; Unique identifier: DRKS00012914.

We investigated the sex-related difference in characteristics and 2-year outcomes after surgical aortic valve replacement (SAVR) by propensity-score matching (PSM). Data from 2 prospective registries, the INSPIRIS RESILIA Durability Registry (INDURE) and IMPACT, were merged, resulting in a total of 933 patients: 735 males and 253 females undergoing first-time SAVR. The PSM was performed to assess the impact of sex on the SAVR outcomes, yielding 433 males and 243 females with comparable baseline characteristics. Females had a lower body mass index (median 27.1 vs 28.0 kg/m2; P = 0.008), fewer bicuspid valves (52% vs 59%; P = 0.036), higher EuroSCORE II (mean 2.3 vs 1.8%; P < 0.001) and Society of Thoracic Surgeons score (mean 1.6 vs 0.9%; P < 0.001), were more often in New York Heart Association functional class III/IV (47% vs 30%; P < 0.001) and angina Canadian Cardiovascular Society III/IV (8.2% vs 4.4%; P < 0.001), but had a lower rate of myocardial infarction (1.9% vs 5.2%; P = 0.028) compared to males. These differences vanished after PSM, except for the EuroSCORE II and Society of Thoracic Surgeons scores, which were still significantly higher in females. Furthermore, females required smaller valves (median diameter 23.0 vs 25.0 mm, P < 0.001). There were no differences in the length of hospital stay (median 8 days) or intensive care unit stay (median 24 vs 25 hours) between the 2 sexes. At 2 years, post-SAVR outcomes were comparable between males and females, even after PSM. Despite females presenting with a significantly higher surgical risk profile, 2-year outcomes following SAVR were comparable between males and females.

Introduction: The management of patients with severe aortic stenosis may differ according to patients’ age. The aim of this analysis was to describe patterns of aortic valve replacement (AVR) use in European countries stratified by age. Methods: Procedure volume data for AVR, including surgical aortic valve replacement (sAVR) and transcatheter aortic valve implantation (TAVI), for the years 2015–2020 were obtained from national databases for twelve European countries (Austria, the Czech Republic, Denmark, England, Finland, France, Germany, Norway, Poland, Spain, Sweden, and Switzerland). Procedure volumes were reported by patient age (<50 years, 5-year age groups between 50 and 85 years, and ≥85 years). Patients per million (PPM) population undergoing AVR each year were calculated using population estimates from Eurostat. Results: AVR PPM varied widely between countries, from 508 PPM in Germany to 174 PPM in Poland in 2020. TAVI rates ranged from 61% in Switzerland and Finland to 25% in Poland. AVR PPM increased with age to a peak at 80–84 years, after which it decreased again. AVR procedures increased from 2015 to 2019 at an average annual rate of 3.9%. AVR increased more substantially in people aged ≥80 years than in younger age groups; these older age groups accounted for 30% of all AVR procedures in 2015 and 35% in 2019. TAVI accounted for an increasing proportion of all AVR procedures as patient age increased; an overall average of 96% of males and 98% of females aged ≥85 years received TAVI as the treatment modality, although adoption of TAVI differed between countries. Conclusions: There is considerable variation in the rates of AVR use and the adoption of TAVI versus sAVR between European countries. The use of TAVI has increased in recent years, particularly for older patients.

Background: Intraoperative hypotension is common in patients having non-cardiac surgery and associated with postoperative acute myocardial injury, acute kidney injury, and mortality. Avoiding intraoperative hypotension is a complex task for anesthesiologists. Using artificial intelligence to predict hypotension from clinical and hemodynamic data is an innovative and intriguing approach. The AcumenTM Hypotension Prediction Index (HPI) software (Edwards Lifesciences; Irvine, CA, USA) was developed using artificial intelligence—specifically machine learning—and predicts hypotension from blood pressure waveform features. We aimed to describe the incidence, duration, severity, and causes of intraoperative hypotension when using HPI monitoring in patients having elective major non-cardiac surgery. Methods: We built up a European, multicenter, prospective, observational registry including at least 700 evaluable patients from five European countries. The registry includes consenting adults (≥18 years) who were scheduled for elective major non-cardiac surgery under general anesthesia that was expected to last at least 120 min and in whom arterial catheter placement and HPI monitoring was planned. The major objectives are to quantify and characterize intraoperative hypotension (defined as a mean arterial pressure [MAP] < 65 mmHg) when using HPI monitoring. This includes the time-weighted average (TWA) MAP < 65 mmHg, area under a MAP of 65 mmHg, the number of episodes of a MAP < 65 mmHg, the proportion of patients with at least one episode (1 min or more) of a MAP < 65 mmHg, and the absolute maximum decrease below a MAP of 65 mmHg. In addition, we will assess causes of intraoperative hypotension and investigate associations between intraoperative hypotension and postoperative outcomes. Discussion: There are only sparse data on the effect of using HPI monitoring on intraoperative hypotension in patients having elective major non-cardiac surgery. Therefore, we built up a European, multicenter, prospective, observational registry to describe the incidence, duration, severity, and causes of intraoperative hypotension when using HPI monitoring in patients having elective major non-cardiac surgery.

Short-term glycemic variability is associated with the risk of hypoglycemia and hyperglycemia in people living with type 1 diabetes and can potentially affect clinical outcomes. Continuous glucose monitoring (CGM) is of increasing importance to evaluate glycemic variability in greater detail. Specific metrics for assessing glycemic variability were proposed, such as the SD of mean glucose level and associated coefficient of variation, and time in target glucose range to guide study designs, therapy and allow people with diabetes more transparency in interpreting their own CGM data. Randomized controlled trials (RCT) and real-world evidence provide complementary information about the efficacy/effectiveness and safety of interventions. Insulin glargine 300 U/mL (Gla-300) has a longer lasting and less variable action than insulin glargine U100 (Gla-100) with a lower risk of hypoglycemia. While insulin degludec U100 (iDeg-100) was associated with lower glucose values but more time below range in one randomized study compared with Gla-300, Gla-300 was associated with a higher per cent time in range, but also above the therapeutic range. However, a real-world study did not find differences during the day between Gla-300 and iDeg-100. The upcoming InRange RCT is the first head-to-head comparison of Gla-300 with iDeg-100 using CGM in an international population using CGM metrics as the primary endpoint. The non-interventional COMET-T real-world study will determine the real-world effectiveness of Gla-300 using CGM metrics and cover a broad spectrum of clinical practice decisions irrespective of the prior basal insulin.

Abstract BackgroundImmunochromatographic rapid antigen tests (RATs) emerged onto the COVID-19 pandemic testing landscape to aid in the rapid diagnosis of people with suspected SARS-CoV-2 infection. RATs are particularly useful where RT-PCR is not immediately available and symptoms suggestive of a high viral load and infectiousness are assumed. Several lateral flow immunoassays have been authorized for use under EUA and/or the CE mark, presenting varying overall clinical performance data generated by the manufacturer or by independent investigators. To compare the real-world clinical performance of commercially available rapid chromatographic immunoassays intended for the qualitative detection of SARS-CoV-2, we performed a systematic meta-analysis of published data.MethodsWe searched the MEDLINE®, Embase, BIOSIS and Derwent Drug File (ProQuest)for manufacturer-independent prospective clinical performance studies comparing SARS-CoV-2 RATs and RT-PCR assays. Only studies on lateral flow assays not needing a separate reader for retrieving the result were included, if data were available on viral load, patients’ symptom status, sample type, and PCR assay used. For better data comparability, recalculation of the studies’ single performance data confidence intervals using the exact Clopper–Pearson method was applied.ResultsWe could include 19 studies (ten peer-reviewed) presenting detailed clinical performance data on 11,209 samples with 2449 RT-PCR-positives out of study prevalence rates between 1.9–100 % and between 50– 100% symptomatic samples. Four studies directly compared two to three different RATs and 15 studies compared one RAT to RT-PCR. Overall specificity ranged, with one test outlier, between 92.4% (87.4– 95.9) and 100% (99.7–100), and overall clinical sensitivity varied between 28.9% (16.4–44.3) and 98.3% (91.1–99.7), depending on assay, population characteristics, viral load, and symptom status. Sensitivity in high-viral-load samples (cycle threshold ≤25) showed a considerable heterogeneity among the assays ranging from 66.7% to 100%.ConclusionOnly two RATs offered sufficient manufacturer-independent, real-world performance data supporting use for the detection of current SARS-CoV-2 infection in symptomatic or high-viral-load patient populations. Reliable positive predictive values require testing of symptomatic patients or asymptomatic individuals only in case of a high pre-test probability. If RATs are used for screening of asymptomatic cases in low-prevalence scenarios, a lower positive predictive value of the result has to be considered.

Systemic antineoplastic treatment agents represent one of the fastest developing medical fields. Oncological treatment is becoming increasingly individualized and new targets with corresponding agents, are constantly being developed. In tandem with this progress, new combinations and algorithms have evolved and patient's outcome have improved. Expanding tumors rely on a growing neovascular network to maintain their increased metabolism, which is caused by an accelerated reproduction rate. Accordingly, interrupting this supply mechanism is a major component of antineoplastic pharmaceutics and is a hallmark of cancer treatment. With advances in cancer treatment, long-term side effects have become an important consideration, especially in cases of neoplasia in young patients. While neuropathy and cardiotoxicity are well documented, vascular adverse events remain poorly understood. The mutual risk factors, like smoking and increased age, complicate the association between the vascular pathology and the earlier antineoplastic therapy. A deeper understanding of the effects of chemotherapy on peripheral arterial disease could lead to more detailed pathophysiological insight into both maladies and to new treatment options.

Minimally invasive cardiac surgery (MICS) via right lateral mini thoracotomy is the gold standard treatment approach for mitral and tricuspid valve disorders. Other selected procedures (e.g. transapical aortic valve implantation, MIDCAB) require a left lateral mini thoracotomy for surgical access. Advantages of MICS over complete sternotomy are well known, but access-related complications post MICS, such as pulmonary herniation, are often underestimated/overlooked. In males, a pulmonary herniation in the proximity of the former thoracotomy is often clinically visible, especially when the intrathoracic pressure rises (e.g. during coughing). In females, clinical symptoms may be hidden by the breast and patients often have unspecific complaints or occasional pain when coughing, making identification of a lung herniation more difficult. Chest computed tomography is the diagnostic tool of choice for pulmonary herniations. Using a series of 20 patients with pulmonary herniation post MICS, we report our findings in diagnosis and treatment of this condition.