永久起搏器在预防心房颤动中的作用

本文总结了用于预防和终止心房颤动的起搏器的类型。窦房结功能异常的病人,心室起搏与较高的心房颤动的发生率相关。有鉴于此,有心房颤动病史、因心动过缓而需要安装起搏器的病人,应该安装双腔或心房起搏生理性起搏器,而不应安装单腔的心室起搏器。     

Evidence for a link between TNFRSF11A and risk of breast cancer

Intracellular signaling mediated by the receptor activator of nuclear factor-κB [Rank, encoded by the tumor necrosis factor receptor superfamily, member 11a (Tnfrsf11a) gene] is fundamental for mammary gland development in mice, regulating the expansion of stem and progenitor cell compartments. Conversely, Rank overexpression in mice promotes abnormal proliferation and impairs differentiation, leading to an increased incidence of tumorigenesis. Here, we show that a common genetic variant near the 5'-end of TNFRSF11A, rs7226991, is associated with breast cancer risk in the general population and among carriers of mutations in the breast cancer 2, early onset (BRCA2) gene. Akin to the results of the Cancer and Genetics Markers of Susceptibility initiative, combined analysis of rs7226991 in two Spanish case-control studies (1,365 controls and 1,323 cases in total) revealed a significant association with risk: odds ratio (OR) = 0.88, 95% confidence interval (CI) 0.78-0.98, P (trend) = 0.025. Subsequent examination of BRCA1 (n = 1,017) and BRCA2 (n = 885) mutation carriers revealed a consistent association in the latter group: weighted hazard ratio ((w)HR) = 0.70; 95% CI 0.55-0.88; and P (trend) = 0.003; compared to BRCA1 mutation carriers, (w)HR = 0.91; 95% CI 0.76-1.10; and P (trend) = 0.33. The results of this study need to be replicated in other populations and with larger numbers of BRCA1/2 mutation carriers.     

Lack of significant effect of bilastine administered at therapeutic and supratherapeutic doses and concomitantly with ketoconazole on ventricular repolarization: results of a thorough QT study (TQTS) with QT-concentration analysis

The effect of bilastine on cardiac repolarization was studied in 30 healthy participants during a multiple-dose, triple-dummy, crossover, thorough QT study that included 5 arms: placebo, active control (400 mg moxifloxacin), bilastine at therapeutic and supratherapeutic doses (20 mg and 100 mg once daily, respectively), and bilastine 20 mg administered with ketoconazole 400 mg. Time-matched, triplicate electrocardiograms (ECGs) were recorded with 13 time points extracted predose and 16 extracted over 72 hours post day 4 dosing. Four QT/RR corrections were implemented: QTcB; QTcF; a linear individual correction (QTcNi), the primary correction; and a nonlinear one (QTcNnl). Moxifloxacin was associated with a significant increase in QTcNi at all time points between 1 and 12 hours, inclusively. Bilastine administration at 20 mg and 100 mg had no clinically significant impact on QTc (maximum increase in QTcNi, 5.02 ms; upper confidence limit [UCL] of the 1-sided, 95% confidence interval, 7.87 ms). Concomitant administration of ketoconazole and bilastine 20 mg induced a clinically relevant increase in QTc (maximum increase in QTcNi, 9.3 ms; UCL, 12.16 ms). This result was most likely related to the cardiac effect of ketoconazole because for all time points, bilastine plasma concentrations were lower than those observed following the supratherapeutic dose.     

Endothelin-1 levels predict endothelial progenitor cell mobilization after acute myocardial infarction

IntroductionEndothelin-1 (ET-1), circulating endothelial cells (CEC) and endothelial progenitor cells (EPC) are well-known modulators of endothelial function with important cardiac effects after an acute myocardial infarction. However, the relationship between them has never been assessed.The objective of the present study was to establish the relationship between ET-1, CEC, and EPC concentrations after ST-elevation myocardial infarction (STEMI).MethodsEndothelin-1, CEC, and EPC levels were measured in 61 patients presenting with a first STEMI. Samples were withdrawn acutely 6–24 h and 1 week after admission. Assessments included reperfusion outcomes (angiography), left ventricular ejection fraction (echocardiography), and 30-day mortality.ResultsMean age was 60.6 ± 12.6 years and 45 (74%) were males. Higher ET-1 plasma levels were associated with lower EPC count after 1 week (7.45 ± 2.53 pg/ml if EPCs in the first quartile vs 5.72 ± 1.49 pg/ml if EPCs in the fourth quartile; P = 0.04).In contrast with CEC and EPC count, higher ET-1 concentrations on admission were associated with Killip ≥ 2 (9.92 ± 2.01 pg/ml vs 7.32 ± 2.13 pg/ml; P < 0.001), post-reperfusion thrombolysis in myocardial infarction (TIMI) < 3 (8.65 ± 2.86 pg/ml vs 5.87 ± 1.93 pg/ml; P = 0.002), myocardial blush grade (MBG) < 3 (7.46 ± 2.48 pg/ml vs 5.99 ± 2.01 pg/ml; P = 0.004) and higher 30-day mortality (10.29 ± 2.02 pg/ml vs 6.57 ± 2.20 pg/ml; P = 0.005).ConclusionsIn STEMI patients, high ET-1 levels on admission predict a lower EPC mobilization after 1 week. Endothelin-1 provides better clinical, angiographic and echocardiographic information for prognosis than do CEC and EPC concentrations.