A case series of LMWH use in pregnancy: Should trough anti-Xa levels guide dosing?

Introduction

Pregnancy is a thrombogenic state, increasing the risk for venous thromboembolism (VTE), and the risk of valve thrombosis amongst women with mechanical heart valves (MHV). While low molecular weight heparins (LMWH) are generally dosed based on weight (i.e., enoxaparin 1 mg/kg every 12 hours), data in pregnant women have shown that weight-based dosing does not consistently achieve target anti-Xa levels. In women with MHV, our practice includes titrating LMWH doses to target both trough and peak anti-Xa levels, while for those with VTE peak anti-Xa levels guide dosing.

Materials/Methods

This retrospective case series included pregnant women requiring LMWH treatment doses with at least 3 peak (+/− trough) anti-Xa levels. Our primary objective was to describe the actual LMWH dose required to achieve targeted anti-Xa levels relative to weight-based dosing in patients with MHV. Secondarily, we compared the same for VTE patients; compared actual dosing between those with MHV and VTE; and examined maternal and fetal outcomes.

Results/Conclusion

Women with MHV (N = 4) required greater than weight-based dosing of enoxaparin (1.35 mg/kg Q12H) to achieve targeted anti-Xa levels. Importantly, achieving target peak anti-Xa levels did not always ensure maintenance of minimum trough levels. VTE patients (N = 12) did not require more enoxaparin (0.96 mg/kg Q12H) than weight based dosing. MHV patients received more enoxaparin compared to VTE patients (P < 0.001). No bleeding or clotting complications were associated with LMWH administration. In pregnant women with MHV at high risk of thromboembolism, LMWH dosing guided by trough and peak anti-Xa levels should be considered.     

Tetralogy of Fallot with restrictive ventricular septal defect by accessory tricuspid leaflet tissue

In tetralogy of Fallot septal defect is usually large because of malalignment of outlet septum, restrictive defect has been reported rarely. We present a case of tetralogy of Fallot with accessory tricuspid leaflet tissue restricting ventricular septal defect. The report includes echocardiographic and catheter images of this rare presentation of tetralogy of Fallot.     

Parachute tricuspid valve in an asymptomatic adult

Parachute tricuspid valve is a rare anomaly usually reported in small children. This report describes transthoracic and trans-oesophageal echocardiographic (TEE) features of parachute mitral valve in an adult patient.     

腭咽闭合不全患者异常声学特点的分析研究

目的:应用VS99-CSL计算机语音声学频谱分析评估系统对病理性语音中的部分元音、辅音音频语图特点进一步分析研究,给予先天性腭咽闭合不全的诊断与治疗提供理论及临床支持。方法:采集单纯性先天腭咽闭合不全患者22例。评估咽成形术后及腭裂术后26例,上述患者针对咽腔情况视诊、blowing test测验及雾镜实验测试综合分析,对较难判断的病例可结合CT进行诊断,单元音:[a、o、e、i、ü]辅音;擦音[s、x]、塞擦[z、j、c、q]实施语音评估对其单元音共振峰和额外共振峰及辅音和元音节的频谱特点进行分析、同时比较各组空白间隙、冲直条、噪音乱纹的出现率,并设定正常对照组。结果:比较发现[a]的共振峰普遍残缺,而[iü]会出现额外附加共振峰,其共振峰均值F1咽成形术后较高,先天性腭咽闭合不全则低。擦音[s、x]、塞擦音[z、j、c、q]实施语图对频谱特点进行分析、同时比较各组空白间隙、冲直条、噪音乱纹的出现频率,嗓音起始时间(voice onsettime,VOT)以及语音清晰度,P<0.01说明正常对照组与病例组有显著性差异。结论:CSAS能客观评价腭咽闭合不全,其获得的语图及相关物理声学参量对腭咽闭合不全临床治诊疗提供理论依据。     

Increased temporal dispersion of myocardial repolarization in myotonic dystrophy type 1: beyond the cardiac conduction system

Objectives

To assess ventricular dysfunction and ventricular interaction after repair of Tetralogy of Fallot (ToF) employing echocardiography speckle-tracking and cardiac magnetic resonance imaging (CMR).

Background

Severe pulmonary regurgitation and right ventricular (RV) dysfunction are common after repair of ToF and may also affect the shape and function of the left ventricle (LV). Recent studies suggest that LV dysfunction may be of particular prognostic value.

Methods and results

Twenty-one consecutive adults with repaired ToF (15 male, mean age 38 ± 11 years, 7 with severe PR) underwent a comprehensive echocardiographic exam including speckle-tracking analysis, CMR and cardiopulmonary exercise testing. Twenty-one subjects without relevant heart disease served as controls. Echocardiographically measured RV diameters correlated with RV volumes obtained from CMR (r = 0.63; p = 0.006). In addition, a close correlation was found between RV and LV function on CMR (r = 0.74, p = 0.002), speckle-tracking LV and RV peak longitudinal 2D strain (r = 0.66, p = 0.003) and mitral and tricuspid annular plain systolic excursion (r = 0.71, p = 0.0003). While LV ejection fraction was normal in the majority of patients and not different from controls, LV longitudinal strain was significantly reduced in ToF patients (− 16.5 ± 3.3 vs. -20.5 ± 2.7%, p = 0.0001).

Conclusion

Left and right ventricular function both by CMR and speckle-tracking is interrelated in adults with repaired ToF. Despite normal LV ejection fraction, 2D longitudinal strain is significantly reduced in ToF patients, suggesting subclinical LV myocardial damage. Considering the potential prognostic value of LV dysfunction in ToF, this measurement may gain importance and should be included in future outcome studies.     

Valvular heart disease and pregnancy

Among women with valvular heart disease, those with mitral stenosis carry the greatest potential for problems during pregnancy. Asymptomatic women with aortic stenosis and only mild or moderate left ventricular outflow obstruction generally tolerate pregnancy well, as do those with regurgitant lesions. In Marfan syndrome, pregnancy should not be undertaken if the aortic root dimension exceeds 4 cm. Even if the aortic root is normal, a small increased risk of dissection is present. Women with well-functioning bioprosthetic valves and normal hemodynamics may safely undertake a pregnancy, although bioprostheses deteriorate rapidly in young people.     

Glycosaminoglycan entrapment by fibrin in engineered heart valve tissues

Tissue engineered heart valves (TEHVs) may provide a permanent solution to congenital heart valve disease by permitting somatic valve growth in the pediatric patient. However, to date, TEHV studies have focused primarily on collagen, the dominant component of valve extracellular matrix (ECM). Temporal decreases in other ECM components, such as the glycosaminoglycans (GAGs), generally decrease as cells produce more collagen under mechanically loaded states; nevertheless, GAGs represent a key component of the valve ECM, providing structural stability and hydration to the leaflets. In an effort to retain GAGs within the engineered constructs, here we investigated the utility of the protein fibrin in combination with a valve-like, cyclic flexure and steady flow (flex–flow) mechanical conditioning culture process using adult human periodontal ligament cells (PLCs). We found both fibrin and flex–flow mechanical components to be independently significant (p < 0.05), and hence important in influencing the DNA, GAG and collagen contents of the engineered tissues. In addition, the interaction of fibrin with flex–flow was found to be significant in the case of collagen; specifically, the combination of these environments promoted PLC collagen production resulting in a significant difference compared to dynamic and statically cultured specimens without fibrin. Histological examination revealed that the GAGs were retained by fibrin entrapment and adhesion, which were subsequently confirmed by additional experiments on native valve tissues. We conclude that fibrin in the flex–flow culture of engineered heart valve tissues: (i) augments PLC-derived collagen production; and (ii) enhances retention of GAGs within the developing ECM.     

聚乙二醇去细胞瓣复合支架联合人主动脉瓣膜间质细胞体外构建组织工程心脏瓣膜

目的:运用聚乙二醇(PEG)交联猪去细胞瓣,共价接枝GRGDSPC多肽(甘氨酸-精氨酸-甘氨酸-天冬氨酸-丝氨酸-脯氨酸-半胱氨酸),并联合人主动脉瓣膜间质细胞(HAVICs)体外构建组织工程心脏瓣膜。方法:通过迈克尔加成反应,将去细胞瓣支架上引入的巯基与枝化状PEG末端丙烯酰基共价结合,使PEG交联去细胞瓣,并行生物力学检测。再利用PEG-去细胞瓣支架上未饱和的丙烯酰基与GRGDSPC多肽末端半胱氨酸的巯基发生迈克尔加成反应,对PEG-去细胞瓣支架行GRGDSPC多肽共价修饰,免疫荧光测定GRGDSPC多肽修饰效果。在RGD-PEG-去细胞瓣复合支架上种植HAVICs,缝制于生物反应器内,体外构建心脏瓣膜。接种2、4、8h后,通过细胞计数观察细胞粘附情况。体外培养10d后行形态学观察和DNA含量测定。结果:力学测试结果显示,PEG-去细胞瓣支架的最大抗张强度较单纯去细胞瓣支架明显提高[(7.53±0.32)Mpa∶(5.65±0.28)Mpa],差异有统计学意义(P<0.05),与天然主动脉瓣的差异无统计学意义(P>0.05)。免疫荧光检测显示,GRGDSPC多肽可有效地与PEG-去细胞瓣共价接枝。不同时段细胞粘附计数及形态学观察提示,RGD-PEG-去细胞瓣复合支架明显促进HAVICs的粘附,并可在瓣膜表面形成连续单细胞层。DNA含量测定提示,RGD-PEG-去细胞瓣复合支架DNA含量明显增高(P<0.05)。结论:PEG交联去细胞瓣可明显改善瓣膜支架力学性能,GRGDSPC多肽接枝的PEG-去细胞瓣复合支架,可促进种子细胞的粘附,改善瓣膜支架生物学性能。