Inverse Relationship Between Membranous Septal Length and the Risk of Atrioventricular Block in Patients Undergoing Transcatheter Aortic Valve Implantation

ObjectivesThis study sought to examine whether imaging of the atrioventricular (AV) membranous septum (MS) by computed tomography (CT) can be used to identify patient-specific anatomic risk of high-degree AV block and permanent pacemaker (PPM) implantation before transcatheter aortic valve implantation (TAVI) with self-expandable valves.BackgroundMS length represents an anatomic surrogate of the distance between the aortic annulus and the bundle of His and may therefore be inversely related to the risk of conduction system abnormalities after TAVI.MethodsSeventy-three consecutive patients with severe aortic stenosis underwent contrast-enhanced CT before TAVI. The aortic annulus, aortic valve, and AV junction were assessed, and MS length was measured in the coronal view.ResultsIn 13 patients (18%), high-degree AV block developed, and 21 patients (29%) received a PPM. Multivariable logistic regression analysis revealed MS length as the most powerful pre-procedural independent predictor of high-degree AV block (odds ratio [OR]: 1.35, 95% confidence interval [CI]: 1.1 to 1.7, p = 0.01) and PPM implantation (OR: 1.43, 95% CI: 1.1 to 1.8, p = 0.002). When taking into account pre- and post-procedural parameters, the difference between MS length and implantation depth emerged as the most powerful independent predictor of high-degree AV block (OR: 1.4, 95% CI: 1.2 to 1.7, p < 0.001), whereas the difference between MS length and implantation depth and calcification in the basal septum were the most powerful independent predictors of PPM implantation (OR: 1.39, 95% CI: 1.2 to 1.7, p < 0.001 and OR: 4.9, 95% CI: 1.2 to 20.5, p = 0.03; respectively).ConclusionsShort MS, insufficient difference between MS length and implantation depth, and the presence of calcification in the basal septum, factors that may all facilitate mechanical compression of the conduction tissue by the implanted valve, predict conduction abnormalities after TAVI with self-expandable valves. CT assessment of membranous septal anatomy provides unique pre-procedural information about the patient-specific propensity for the risk of AV block.     

Surgical Sutureless and Transcatheter Aortic Valves: Hemodynamic Performance and Clinical Outcomes in Propensity Score-Matched High-Risk Populations With Severe Aortic Stenosis

ObjectivesIn propensity score–matched patients with severe aortic stenosis treated with surgical aortic valve replacement (AVR) with the 3f Enable sutureless prosthesis (Medtronic, Minneapolis, Minnesota) or transcatheter aortic valve replacement (TAVR), the hemodynamic performance of both valves and mid-term survival of patients were evaluated.BackgroundData on hemodynamic performance of surgical sutureless bioprostheses in high operative risk patients with aortic stenosis are scarce.MethodsOf 258 patients undergoing TAVR or surgical aortic valve replacement with the 3f Enable valve, 80 (79 ± 5 years of age, 100% men) were included in the current analysis on the basis of propensity score 1:1 matching for baseline clinical and hemodynamic characteristics. All patients had hemodynamic echocardiographic evaluation at baseline and discharge. Mid-term survival was analyzed.ResultsCompared with the 3f Enable valve, TAVR prostheses (Edwards SAPIEN XT [Edwards Lifesciences, Irvine, California] and CoreValve [Medtronic]) had larger effective orifice area index (1.00 ± 0.30 cm²/m² vs. 0.76 ± 0.22 cm²/m²; p < 0.001), lower pressure gradient (8.14 ± 4.21 mm Hg vs. 10.72 ± 4.01 mm Hg; p = 0.006), less frequent prosthesis-patient mismatch (30.0% vs. 67.5%; p = 0.001), and low flow (46.2% vs. 72.5%; p = 0.02), but more frequent aortic regurgitation (87.5% vs. 20.0%; p < 0.001). The presence of prosthesis-patient mismatch was independently associated with a low-flow state at discharge (odds ratio: 4.70; p = 0.004) and independently associated with the use of the sutureless prosthesis (odds ratio: 3.90; p = 0.02). However, the survival of the 2 groups was comparable after 1.5-year (interquartile range: 0.79 to 2.01 years) follow-up (log-rank test, p = 0.95).ConclusionsTAVR prostheses demonstrated better hemodynamics than the 3f Enable valve but a higher incidence of aortic regurgitation. However, these differences did not influence mid-term survival of patients.     

Treatment of Symptomatic Severe Aortic Stenosis With a Novel Resheathable Supra-Annular Self-Expanding Transcatheter Aortic Valve System

ObjectivesThe purpose of this study was to prospectively evaluate the safety and clinical performance of the CoreValve Evolut R transcatheter aortic valve replacement (TAVR) system (Medtronic, Inc., Minneapolis, Minnesota) in a single-arm, multicenter pivotal study in high- or extreme-risk patients with symptomatic aortic valve stenosis.BackgroundAlthough outcomes following TAVR are improving, challenges still exist. The repositionable 14-F equivalent CoreValve Evolut R TAVR system was developed to mitigate some of these challenges.MethodsSuitable patients (n = 60) underwent TAVR with a 26- or 29-mm Evolut R valve. Primary safety endpoints were mortality and stroke at 30 days. Primary clinical performance endpoints were device success per the VARC-2 (Valve Academic Research Consortium-2) and the percent of patients with mild or less aortic regurgitation 24 h to 7 days post-procedure.ResultsPatients (66.7% female; mean age 82.8 ± 6.1 years; Society of Thoracic Surgeons Score 7.0 ± 3.7%) underwent TAVR via the transfemoral route in 98.3%, using a 29-mm valve in 68.3% of patients. All attempts at repositioning were successful. No death or stroke was observed up to 30 days. The VARC-2 overall device success rate was 78.6%. Paravalvular regurgitation post TAVR was mild or less in 96.6%, moderate in 3.4%, and severe in 0% at 30 days. Major vascular complications occurred in 8.3%, and permanent pacemaker implantation was required in 11.7% of patients.ConclusionsThe repositionable 14-F equivalent Evolut R TAVR system is safe and effective at treating high-risk symptomatic aortic stenosis patients. Repositioning was successful when required in all patients, with low rates of moderate or severe paravalvular aortic regurgitation and low permanent pacemaker implantation. (The Medtronic CoreValve™ Evolut R™ CE Mark Clinical Study; NCT01876420)     

Prediction of Long-Term Incidence of Chronic Cardiovascular and Cardiopulmonary Diseases in Primary Care Patients for Population Health Monitoring: The Intermountain Chronic Disease Model (ICHRON)

ObjectiveTo apply the practical parsimonious modeling method of the Intermountain Mortality Risk Score in a primary care environment to predict chronic disease (ChrD) onset.Patients and MethodsPrimary care patients free of ChrD (women: n=98,711; men: n=45,543) were evaluated to develop (70% [n=95,882] of patients) and validate (the other 30% [n=48,372]) the sex-specific Intermountain Chronic Disease Risk Score (ICHRON) if seen initially between January 1, 2003, and December 31, 2005. The sex-specific ICHRON was composed of comprehensive metabolic profile and complete blood count components and age. The primary outcome was the first diagnosis of coronary artery disease, myocardial infarction, heart failure, atrial fibrillation, stroke, diabetes, renal failure, chronic obstructive pulmonary disease, peripheral vascular disease, or dementia within 3 years of baseline.ResultsAt 3 years, 9.0% of men (mean age, 44±16 years) and 6.6% of women (mean age, 42±16 years) received a diagnosis of ChrD. In the derivation population, C-statistics were 0.783 (95% CI, 0.774-0.791) for men and 0.774 (95% CI, 0.767-0.781) for women. In the validation population, C-statistics were 0.774 (95% CI, 0.762-0.786) for men and 0.762 (95% CI, 0.752-0.772) for women. Evaluation of 10-year outcomes for ICHRON and analysis of its association with each outcome individually at 3 years revealed similar predictive ability.ConclusionAn augmented intelligence clinical decision tool for primary care, ICHRON, is developed using common laboratory parameters, which provides good discrimination of ChrD risk at 3 and 10 years.     

聚丙烯补片与脱细胞真皮基质补片及传统方法修复战伤性腹壁软组织

背景：近年来随着各种新型的人工合成修补材料问世,应用这类材料修补疾病所致的腹壁缺损也取得了很好的效果,但应用于战伤腹壁缺损的研究较少。 目的：比较脱细胞真皮基质、聚丙烯补片以及传统方法修补战伤腹壁缺损的有效性和安全性。 设计、时间及地点：随机对照动物实验,于2008-01/08在解放军第四军医大学西京医院及唐都医院动物实验外科实验室完成。 材料：脱细胞真皮基质由烟台正海生物技术有限公司提供;聚丙烯补片购于北京。 方法：27只成年杂种犬制作腹部开放伤动物模型后,随机分为3组,分别以脱细胞真皮基质、聚丙烯补片、传统修复方法进行修补。 主要观察指标：3组分别于术后1,3,6个月时取材行光镜检查及抗拉力强度测定。 结果：全部动物无伤口裂开、无腹壁疝形成,脱细胞真皮基质修补组脏面未与内脏粘连,聚丙烯补片修补组均与内脏粘连。组织切片苏木精-伊红染色检查表明脱细胞真皮基质较聚丙烯补片、传统修补更有利于成纤维细胞及血管形成,6个月内脱细胞真皮基质可逐渐降解替代;6个月时聚丙烯补片仍有炎症反应,表现了长期的异物影响;传统修补只是肌肉之间简单的瘢痕愈合,增殖较少,生长较慢。抗拉力试验结果提示在3个阶段除6个月时脱细胞真皮基质修补处与聚丙烯补片修补处抗拉力强度相等外,余均提示在抗拉力强度上脱细胞真皮基质修补处>聚丙烯补片修补处>传统方法修补处。 结论：脱细胞真皮基质修复战伤腹壁缺损的效果等同于聚丙烯补片,均优于传统修复方法,安全性优于聚丙烯补片。     

Dissociation kinetics of the thyrotropin-receptor complex. Characterization of a slowly dissociable component

The kinetics of the dissociation of thyrotropin (TSH) from human thyroid plasma membranes were studied in an attempt to further understand the molecular dynamics of the TSH--receptor interaction. Dissociation of bound [125I]TSH from thyroid plasma membranes was a biphasic process consisting of rapidly and slowly dissociable components, RDC and SDC, respectively. The dilution induced dissociation of bound [125I]TSH was enhanced by the addition of excess TSH (DEC). DEC was proportional to the dose of unlabeled TSH and its magnitude increased linearly with temperature. These results are in contrast to those reported for the kinetics of [125I]insulin dissociation. The functional significance of DEC remains largely unexplained. It was found that the fraction of SDC was dependent upon time of association in a temperature-dependent and apparently saturable process. It could not be attributed to alterations in the electrophoretic, immunologic or binding properties of [125I]TSH. Furthermore, no correlation was observed between generation of SDC and change in the Scatchard profile of TSH binding, in contrast to studies on growth hormone. These data suggest that, like some other polypeptide hormones, binding of TSH to its receptor does not proceed according to laws describing simple, rapidly reversible, bimolecular reactions. Furthermore, bound TSH undergoes a receptor-mediated conversion from a rapidly to a slowly dissociable state with time of incubation.     

PPM1B and P-IKKβ expression levels correlated inversely with rat gastrocnemius atrophy after denervation

Activated inhibitor of nuclear factor-κB kinase β (IKKβ) is necessary and sufficient for denervated skeletal muscle atrophy. Although several studies have shown that Mg²⁺/Mn²⁺-dependent protein phosphatase 1B (PPM1B) inactivated IKKβ, few studies have investigated the role of PPM1B in denervated skeletal muscle. In this study, we aim to explore the expression and significance of PPM1B and phosphorylated IKKβ (P-IKKβ) during atrophy of the denervated gastrocnemius. Thirty young adult female Wistar rats were subjected to right sciatic nerve transection and were sacrificed at 0 (control), 2, 7, 14, and 28 days after denervation surgery. The gastrocnemius was removed from both the denervated and the contralateral limb. The muscle wet weight ratio was calculated as the ratio of the wet weight of the denervated gastrocnemius to that of the contralateral gastrocnemius. RT-PCR and Western blot analysis showed that mRNA and protein levels of PPM1B were significantly lower than those of the control group at different times after the initiation of denervation, while P-IKKβ showed the opposite trends. PPM1B protein expression persistently decreased while P-IKKβ expression persistently increased for 28 days after denervation. PPM1B expression correlated negatively with P-IKKβ expression by the Spearman test, whereas decreasing PPM1B expression correlated positively with the muscle wet weight ratio. The expression levels of PPM1B and P-IKKβ were closely associated with atrophy in skeletal denervated muscle. These results suggest that PPM1B and P-IKKβ could be markers in skeletal muscle atrophy.