Zhang Duanzhen

ASSA14-03-37 Study of effects of simvastatin on proliferation, migration and adhension of rat smooth muscle progenitor cells

Background To investigate the effects of simvastatin on differentiation and proliferation of rat smooth muscle progenitor cells (SPCs) and identification of compounds that inhibit SPCs differentiation and proliferation for substantial clinical usefulness. Methods Total mononuclear cells (MNCs) were isolated from marrow of rats by Ficoll density gradient centrifugation method, and then plated on fibronectin-coated culture dishes. Fresh isolated MNCs were treated with simvastatin (0.01∼10 μmol/l) or vehicle control for 8 d. SPCs were characterised as adherent cells positive for α-SMA by indirect immunofluorescent staining. After 8 days cultured, attached cells were treated with simvastatin (0.01∼10 μmol/l) or vehicle control for 24 h. The proliferation and migration of SPCs were assayed with 3H-TdR incorporation and modified Boyden chamber assay respectively. SPCs adhesion assay was performed by replating those on fibronectin-coated dishes and counting the adherent cells. Results Simvastatin potently inhibited SPCs outgrowth. The number of SPCs at 8 days was dramatically decreased by simvatatin. At a concentration as low as 0.01 μmol/l, simvastatin significantly reduced 7.5 ± 5.4% of SPCs (0.01 μmol/l simvastatin vs control: 79 ± 5 vs 85 ± 4, n = 5, p < 0.05). Simvastatin also inhibited SPCs proliferation in a dose-dependent manner, simvastatin significantly reduced 5.8 ± 3.1% of SPCs at a concentration as low as 0.01 μmol/l for 24 h (0.01 μmol/l simvastatin vs control: 3833 ± 126 vs 4070 ± 184, n = 5, p < 0.05). In addition, sirolims also inhibited SPCs migratory and adhesive capacity in a concentration-dependent manner. Conclusion Simvastatin could inhibit the differentiation, proliferation and migration of rat smooth muscle progenitor cells.

ASSA14-14-03 Clinical analysis of Down's syndrome with congenital heart diseases

Background To analyse congenital heart deformity and haemodynamic data of Down’s syndrome. Methods We diagnosed 36 patients of congenital heart disease patients with Down syndrome by transthoracic two-dimensional echocardiography, colour Doppler flow imaging and right heart catheterization or angiocardiography from July 2008 to October 2012. This article analysed 36 cases of clinical data of Down’s syndrome with congenital heart disease and its hemodynamics. Results Among 36 cases, including VSD 10 cases, AVSD 6 cases, PDA 6 cases, ASD 2 cases, ASD + PDA 2 cases, ASD + VSD 1 case, ASD + PDA + VSD 1 case, VSD + PDA 4 cases, PDA + BAV 1 case, TOF 2 cases, TOF + ASD 1 case in which 18 patients had pulmonary hypertension, including 5 cases of resistant pulmonary arterial hypertension. Conclusions In cardiovascular malformations with Down syndrome, VSD (28%), AVSD (17%) and PDA (17%) are most common and were often associated with ASD or TOF. In patients absent of pulmonary artery stenosis, there were half of them combined with pulmonary artery hypertension.

ASSA14-14-08 Relationship of secundum atrial seplal defect with pulmonary arterial pressure in children less than 5 years old

Background Objective of this study to discover the relationship between secondary atrial septal defect (ASD) and pulmonary arterial pressure (PAP) in children less than 5 years old. Methods Patients whose ages were less than 5 years old were admitted and underwent percutaneous occlusion of ASD with occluder in general anaesthesia with ketamine in General Hospital of Shenyang Military Command from April, 2000 to January, 2011. The patients were divided into different groups according to size of the ASD and PAH. Results 189 patients were concluded, male was 77 cases (40.7 per cent), female was 112 (59.3 per cent), ratio was 1:1.5, mean ages were 4.1 ± 0.9 years old (range from 2 to 5 years), mean weights were 17.2 ± 3.6 kilograms (range from 10.0 to 30.0 kg), mean highs were 104.9 ± 9.2 cm (range from 77 to 135 cm), mean body surface areas (BSA) were 0.71 ± 0.10 m2 (range from 0.46 to 1.02 m2), mean sizes of ASD were 12.6 ± 4.8 mm (range from 5 to 29 mm), mean sizes of ASD modified by BSA were 18.0 ± 7.0 mm/ m2 (range from 5.3 to 38.9 mm/ m2). Mean systolic PAPs were 41.1 ± 8.9 mmHg (range from 15 to 67 mmHg), mean diastolic PAPs were 16.8 ± 6.5 mmHg (range from 3 to 45 mmHg), mean PAPs were 24.9 ± 6.7 mmHg (range from 12 to 48 mmHg). 159 patients (89.4%) had pulmonary arterial hypertension measured by right heart catheterization (RHC), but no patient had PAH by echocardiography. PAPs had no difference in different size ASDs (p >0.05). Conclusions There was no relationship between the sizes of ASD and PAP in children less than 5 years old. PAH maybe been not caused by shunts through ASD.

ASSA13-17-8 Interventional Therapy of Combined Congenital Heart Disease

Objective To evaluate the interventional therapeutic strategy and effect of one-stage interventional therapy of 109 patients’ with combined congenital heart idsease. Methods From June 2000 to October 2012, 109 cases with combined congenital heart disease underwent one-stage interventional therapy. There are 38 males and 71 females ranging from 1 to 56 years old (13.8 +/- 14.6). All patients had been diagnosed by X-ray, ECG, echocardiogram, right heart catheterization and cardiac angiography before the interventional therapy. There were 12 cases with Atrial septal defect (ASD) and patent ductus arteriosus (PDA), 39 cases with ASD and pulmonary valvular stenosis (PS), 25 cases with ASD and ventricular septal defect, 1 case with ASD and mitral valve stenosis (MS), 23 cases with VSD and PDA, 8 cases with PDA and PS, 1 case with ASD and PDA and PS. The interventional therapeutic sequence was percutaneous balloon pulmonary valvuloplasty (PBPV) or percutaneous balloon mitral valvuloplasty, VSD closure, PDA closure, ASD closure in turn. And to evaluate the therapeutic effect by echocardiogram, cardiac angiography or cardiac chamber piezometry after procedure immediately. All patients were enforced X-ray, ECG, echocardiogram on 2d, 1, 3 and 6 months after operation for the follow-up. Results All patients were treated successfully. No complications occurred during the procedure. No residual shunt and dislocation of the devices were found. In the patients with PS, the systolic gradient pressure across the pulmonary valve decreased meet a criterion after operation. In 1 case with ASD and mitral valve, the mitral valve orifice areas increased markably after procedure. During the period of follow-up, the enlarged chambers heart were diminished progressively and all the occluders fixed wel1, X-ray examination showed that pulmonary vascularity diminished significantly, and there was no severe complication in all patients by echocardiogram. Conclusions Though the operation is more difficult and the interventional technic is more skillful, but multiple transcatheter interventions in the same session are feasible, safe and effective with satisfactory good results. However, a satisfactory result can be obtained from suitable indications by TTE before operation, proper algorithm of procedures and standardised manipulations.

ASSA13-17-1 Clinical Analysis of Treatment For 1149 Cases of Membranous Ventricular Septal Defect by Interventional Therapy in Children

Objective To assess the characteristics and clinical experience of treatment for paediatric ventricular septal defect by interventional therapy. Methods We collected 1149 children with VSD who received interventional therapy from 2001 June to 2012 February. There were 578 males and 571 females, age 2.5–16 (6.8 ± 3.1) years old and weight 8–54 (24.7 ± 10.6) kg. III-IVsystolic regurgitant murmur could be heard at left sternal border between 3–4 intercostal space, pulmonic second sound enhanced or split. UCG showed the diameter of VSD was 2–8 (4.3 ± 1.1) mm. Left ventricular angiography showed the left ventricular surface is 4 ∼ 20 (6.38 ± 3.17) mm, right ventricular surface is 3 ∼ 10 (3.81 ± 1.75) mm and the distance from upper VSD margin to aortic valve is 0 ∼ 6 (2.67 ± 1.61) mm. 464 patients combined with membranous ventricular septal aneurysm, 15 patients combined with patent ductus arteriosus, 16 patients combined with atrial septal defect and 4 patients combined with muscular VSD. Results The closure was successful conducted in 1125 patients and the success rate was 98.2%. The diameters of occluder were 4–16 (7.56 ± 2.12) mm. The patients who combined with PDA or ASD, VSD was firsted closed and then PDA or ASD. The patients combined with muscular VSD received occlusion simultaneously. 1061 patients (94.3%) had no shunt instantly, 38 patients (3.4%) had a small shunt and 26 patients (2.3%) had a trace of shunt. 1 cases of postoperative occluder shedding and the occluder was removed and patient received surgical repair of ventricular septal defect. 11 cases of postoperative III degree AVB, 1 patient underwent surgical operation and the rest recovered. 1 patient had III degree AVB 3 years after the occlusion and returned to normal after treatment. 75 cases of complete left bundle branch block, 3 patients did not recovered in the follow up and the rest became normal or not complete left bundle branch block. 1 cases of postoperative hematuria and the symptom disappeared after treatment. Conclusions Strictly indications, standardised operation, proficient skill are the keys to reduce complications and improve the success rate in interventional therapy of VSD. Occlusion of paediatric membrane VSD is a safe, reliable, effective treatment. But its long-term efficacy still need long-term follow-up.

ASSA14-14-07 Expressions of endothelin-converting enzyme in primary cultured atrial myocytes after rapid electrical-field stimulation

Background To study the expressions of endothelin-converting enzyme (ECE2) at early stages of atrial fibrillation in a rapid paced primary cultured atrial myocyte model. Methods Primary rat atrial myocytes were cultured and a rapid paced cell model was established. The atrial cells were divided into five groups with pacing durations within 0 to 24 h. The polymerase chain reaction (RT-PCR) and Western blot (WB) were applied to detect the messenger ribonucleic acid (mRNA) and proteins expression of ECE2. Results mRNA expression of ECE2 increased after 3 h of rapid pacing and continued to elevate in a time dependent manner. Similarly, changes of ECE2 protein were paralleled with mRNA expression. Conclusion Expressions of ECE2 increased in early phase of rapid paced atrial myocytes. It implicated the ECE2 and endothlin-1 was implicated in pathological remodelling of atrial fibrillation.

ASSA13-10-3 The Value of Colour Doppler Echocardiography in the Elderly During the Procedure of Patent Ductus Arteriosus Occlusion

Background To investigate the value of colour Doppler echocardiography (CDE) in the closure of patent ductus arteriosus (PDA) in the elderly. Methods Before the occlusion, screening the indicantions for twenty-five elderly patients with PDA by CDE. Using the shunt flow signal of colour Doppler flow imaging (CDFI) to estimate the pulmonary side diameter of PDA, compare with the angiocardiography and determine its accuracy through statistics. Using the continuous wave Doppler (CW) to measure peak velocity of tricuspid regurgitation and estimate cross-tricuspid pressure gradient according to the simplified Bernoulli equation ΔP = 4V2, together with the inherent right atrial pressure to estimate pulmonary artery pressure. Then compare cross-tricuspid pressure gradient and pulmonary artery pressure with cardiac catheterization. Determine its accuracy through statistics. All patients underwent interventional therapy and determine the efficacy of occlusion by CDE. Results all the occlusion of the elderly patients with PDA was successful through the examination by CDE. The diameter of the PDA pulmonary side estimated by the shunt flow signal had a positive correlation with angiocardiography (r = 0.71, P < 0.001). Pulmonary artery pressure estimated by the CW had a positive correlation with cardiac catheterization contrast (r = 0.63, P < 0.001). Conclusions CDE has an important value in the elderly during the procedure of patent ductus arteriosus occlusion. Using CDFI to estimate PDA pulmonary side diameter and CW to estimate pulmonary artery pressure before the occlusion is the key to screen the indication of occlusion. And it is also important for using CDFI to observe whether there was a residual PDA shunt after transcatheter closure.

ASSA13-15-6 Transcatheter Closure of Patent Ductus Arteriosus with Severe Pulmonary Hypertension Using Domestic Occluder in Adults

Background To evaluate the clinical efficacy of transcatheter closure of patent ductus arteriosus (PDA) with severe pulmonary hypertention using domestic occluder in adults. Methods From July 2000 to July 2011.82 adult patients (13 male, 69 females) were treated by transcatheter closure with domestic occluder. Patients mean age was 36.6years (ranging 18 to 60 years) and the mean PDA diameter at its narrowsest segment was (9.6 ± 2.6) (ranging 6.0 to 16.0) mm. 6 patients of them were treated with sildenafil and/or bosentan before PDA closure. All patients accepted contrast examination of aorta arch-descendens before transcatheter treatment. Patients were classified according to Krichenko grouping method, type A consisted of 35 patients, type B consisted of 4, type C 40 cases, and type E 3 cases. Duct occluder was used in 58, atrial septal defect closure device in 3 and muscular ventricular septal defect closure device in 5. The achievement of permanent transcatheter closure was decided according to the change of the pulmonary arterial pressure, aortic pressure and oxygen saturation. Results The devices were successfully placed in all patients except three patients owing to the resistance of pulmonary hypertention. The systolic pulmonary pressure decreased from (97.3 ± 20.4) (range 70 to 140) mmHg to (51.2 ± 19.4) (33 to 109)mmHg, and the mean pulmonary pressure decreased from (71.2 ± 13.5) (51 to 105) mmHg to (36.4 ± 15.1)(22 to 71)mmHg. Complete angiographic closure was seen 10 minutes after the device deployment in 52 out of 82 patients (63.4%), while trivial to small leak was present in 30 (36.6%). During the occlusion, the average X-ray exposure duration was 16.9 +/- 10.3 minutes, occlusion time was 83.5 +/- 39.2 minutes. 15 of them with systolic pulmonary artery pressure > 70 mmHg after PDA closure were treated with sildenafil or/and bosentan. Complete echocardiographic closure was demonstrated in 77 out of 79 patients (97.5%) at 1 month, and 100% at 6-month follow-up in all patients. Among successful patients, the dimensions of the left atrium, left ventricle and pulmonary artery attenuated considerably in follow-up except for two patients. There were no PDA recanalization and migration of devices after the complete occlusion during following up. Conclusions Transcatheter closure of patent ductus arteriosus with severe pulmonary hypertention using domestic occluder is a safe and effective interventional method in adults.

ASSA13-10-24 Clinical Study of the Left Ventricular Function For Atrial Septal Defect in Adult with Pulmonary Arterial Hypertension

Background To assess the left ventricular function of ASD with PAH patients and to determine whether the left ventricular function and pulmonary pressure could run better after transcatheter closure by echocardiography. Methods There were 75 patients with ASD aged ≥ 40 years, 15 males and 60 females, divided them two groups. (1) PAH group: 36 patients with ASD associated with PAH, 6 males and 30 females, aged from 41 to 74 (mean age 51.7 ± 9.3) years, ASD diameter aged from 15 to 37 (mean 22.9 ± 8.1) mm by using transthoracic echocardiogram (TTE). Systolic pulmonary artery pressure (sPAP) 40 ∼ 107 (57.8 ± 16.0) mmHg, diastolic pulmonary artery pressure (dPAP) 10 ∼ 40 (22.0 ± 5.8)mmHg, mean pulmonary artery pressure (mPAP) 31 ∼ 62 (37.1 ± 7.7) mmHg were measured by using cardiac catheterization. (2) No PAH group (control group): there were 39 patients, 9 males and 30 females, aged from 40 to 63 (mean age 49.3 ± 6.0) years, ASD diameter aged from 8 to 33 (mean 20.6 ± 6.8) mm by using TTE. The sPAP 22 ∼ 38 (28.9 ± 3.9) mmHg, dPAP3 ∼ 20(10 ± 3.8) mmHg, mPAP10 ∼ 19 (15.9 ± 2.8) mmHg were measured by using cardiac catheterization. Before operation, left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), left ventricular stroke volume (LVSV) and left ventricular ejection fraction (LVEF) were measured by using TTE. The sPAP obtained by echocardiograPAHy Doppler according to the tricuspid regurgitation gradient pressure of the ASD with PAH patients. Cardiac catheterization was performed before interventional therapy, sPAP, dPAP, mPAP, Qp/Qs were measured. ASO with a diameter ranging from 18 to 42 (30.8 ± 9.1) mm were placed in PAH group, 3 patients of them with severe PAH required a fenestrated device. The immediate sPAP were measured 28 ∼ 95 (42.7 ± 15.4) mmHg after transcatheter closure, mPAP were 24 ∼ 58 (30.1 ± 6.7) mmHg. ASO with a diameter ranging from 9 to 40 (27.5 ± 7.4) mm were placed in control group. Echocardiography were made at 1 day, 1 ∼ 3 months after the procedure. Results The LVEDD, LVEDV, LVSV and LVEF of PAH group were all smaller than those of no PAH group. The immediate sPAP, mPAP decreased significant after transcatheter closure. The LVEDD, LVEDV, LVSV and LVEF increased significantly after operation 1 day, whereas LVESD, LVESV were unchanged. The LVEDD, LVEDV, LVSV and LVEF improved 1 ∼ 3 months follow-up. The sPAP decreased significant of the patients with severe PAH, who had the indication could implant a fenestrated ASO, and left ventricular function improved at 1day, 1 ∼ 3 months after the procedure. Conclusions The left ventricular function lesion of the ASD patients with PAH were more severe than the ASD patients, the left ventricular function improved after transcatheter closure, so interventional therapy could prevent the left ventricular function from deterioration.

ASSA13-10-2 Efficacy and Safety of Bosentan in Patients with Pulmonary Arterial Hypertension Secondary to Congenital Heart Disease

Background Pulmonary arterial hypertension (PAH) is a major complication of congenital heart disease (CHD), causing increase morbidity and mortality with age. Sustained increase in the pulmonary arterial pressure (PAP) may result in progressive pulmonary vascular remodelling and eventually lead to irreversible changes including extensive intimal injury, obliteration, adventitial fibrosis and smooth muscle cell proliferation. In recent years, insight into the pathogenesis of PAH has resulted in the development of therapeutic strategies for PAH including endothelin receptor antagonists, prostacyclin analogues and phosphodiesterase-5 inhibitors. Endothelin has a key role in the pathobiology of PAH, exerting vasoconstrictor and mitogenic effects by binding to two distinct receptor isoforms in the pulmonary vascular smooth musc-le cells. Bosentan, an orally active dual endothelin receptor antagonist, has been shown to improve exercise capacity, hemodynamics in patients with idiopathic, chronic thromboembolic, and connective tissue disease-associated PAH. However the data of efficacy and safety of bosentan in patients with CHD and PAH is limited. Objective The present study aimed to investigate the efficiency and safety of dual endothelin receptor antagonist bosentan in patients with CHD and severe PAH. Methods Between May 2008 and January 2011, a total of 18 patients with severe PAH secondary to left-to-right shunt CHD were treated with bosentan. All patients underwent cardiac evaluation, including reviewing medical history, physical examination, electrocardiogram and echocardiogram, and cardiac catheterization. The patients with IPAH or PAH secondary to valvular heart diseases, complex CHDs, heart failure (≥NYHA Class III) and other system diseases, and those who had a positive response during acute vasodilator test were excluded from this study. All the patients were treated with bosentan as well as digoxin, diuretics and warfarin for 6 months. Oral bosentan was initiated at 62.5 mg twice daily, increasing after 4 weeks to 125 mg twice daily thereafter in patients weighing > 40 kg and initiated at 31.25 mg twice daily, increasing after 4 weeks to 62.5 mg twice daily in patients weighing ≤40kg. Patients were assessed at 1-month intervals using physical examination, 6-minute walk test, complete blood count and blood biochemistry. Electrocardiogram, X-ray, echocardiogram and right heart catheterization were repeated 6 months after treatment with bosentan. Results There were 6 males and 12 females with age ranging from 9 to 55 (28.7 ± 11.3) years in this series. The basic defects included atrial septal defect (ASD; n = 6), ventricular septal defect (VSD; n = 4) and patent ductus arteriosus (PDA; n = 8). The echocardiogram showed right ventricular diameter (RVD) of 26 ± 8 mm, tricuspid regurgitation speed (VP) of 5.0 ± 0.7 m/s, transtricuspid pressure gradient (PGTV) of 100 ± 26 mmHg, left ventricular end-diastolic diameter (LVEDD) of 37 ± 5mm, left ventricular end-diastolic volume (LVEDV) of 51 ± 21 ml and left ventricular ejection fraction (LVEF) of 0.71 ± 0.06. Right heart catheterization showed oxygen saturation (SaO2) of femoral artery blood of 88.7 ± 5.9%, systolic pulmonary artirial pressure (sPAP) of 115 ± 19 mmHg (1mmHg = 0.133kp), diastolic pulmonary arterial pressure (dPAP) of 63 ± 13 mmHg, mean pulmonary artery pressure (mPAP) of 81 ± 15 mmHg, pulmonary-to-systemic flow (Qp/Qs) ratio of 0.76 ± 0.24 and pulmonary vascular resistance (PVR) of 19.6 ± 7.7 Woods. Six months after treatment with bosentan, echocardiogram showed no significant changes in right ventricular diameter (24 ± 8 mm, P > 0.05), VP (4.7 ± 0.4 m/s, P > 0.05), PGTV (93.3 ± 13.7 mmHg, P > 0.05), LVEDD (39 ± 4 mm, P > 0.05), LVEDV (60 ± 20 ml, P > 0.05), and LVEF (0.72 ± 0.07, P > 0.05). However, 6-minute walk distance (6-MWD) increased from 353 ± 101 to 480 ± 81 m (P < 0.05). Although no significant changes were observed in sPAP (113 ± 15 mmHg, P > 0.05), dPAP (59 ± 14 mmHg, P > 0.05) and mPAP (78 ± 10 mmHg, P > 0.05), the SaO2 of femoral artery blood and Qp/Qs ratio were increased to 91.0 ± 3.2% (P < 0.05) and 1.02 ± 0.35 (P < 0.05), and PVR was decreased to 15.3 ± 3.6 Woods (P < 0.05), respectively at 6 months after treatment. There was no marked change in white blood cells, red blood cells, haemoglobin and platelet, urea nitrogen and creatinine, and transaminases in all but 2 who had a transient increase in transaminases at one month after being treated with bosentan. Conclusions Bosentan was well tolerated and effective for improving exercise capacity and hemodynamics in patients with PAH secondary to CHD. Different to IPAH and PAH secondary to other diseases, bosentan therapy did not cause decrease in pulmonary arterial pressure but PVR and increase in Qp/Qs ratio.