Acute effects of Rho-kinase inhibitor fasudil on pulmonary arterial hypertension in patients with congenital heart defects.

BACKGROUND: We investigated the acute vasodilator effects of i.v. fasudil, a specific Rho-kinase inhibitor, on pulmonary circulation in patients with congenital heart defects (CHD) and severe pulmonary arterial hypertension (PAH). METHODS AND RESULTS: Thirty-five patients (34.23±12.10 years old) with CHD and severe PAH were consecutively enrolled. All patients underwent heart catheterization. At baseline and 30 min after initiation of i.v. fasudil, the following hemodynamic parameters were measured and calculated: right atrial pressure, pulmonary and systemic artery pressure (PAP and SAP), pulmonary and systemic vascular resistance, pulmonary-to-systemic blood pressure ratio (Pp/Ps), pulmonary-to-systemic blood flow ratio (Qp/Qs), cardiac index (CI) and artery oxygen saturation (SaO2). After fasudil treatment, marked decrease in mean PAP (mPAP), pulmonary vascular resistance (PVR), total pulmonary resistance, pulmonary-to-systemic vascular resistance ratio (Rp/Rs) and mean Pp/Ps (mPp/Ps) was found, while Qp/Qs increased significantly without affecting CI and SAP. mPAP, PVR, Rp/Rs and Qp/Qs tended to be improved more significantly in the post-tricuspid shunt group compared with the pre-tricuspid shunt group. CONCLUSIONS: Fasudil was well tolerated in patients with CHD and severe PAH, and significantly reduced PAP and PVR without affecting CI, SAP or SaO2.

Promotion of artery occlusion in dogs by percutaneous rotational atherectomy.

BACKGROUND: This study aims to offer experimental data and indirect evidences for the application of percutaneous rotational atherectomy to treat patent ductus arteriosus (PDA). METHODS: Eleven dogs (6 male dogs and 5 female dogs; aged 14-20 months, with an average of 16.7±3.2 months; weight 20-25 kg, with an average of 22.7±2.5 kg) were enrolled in this study. The diameters of the left and right arteries ranged from 3.2 to 4.8 mm (average 3.9±0.6 mm) on percutaneous angiography. Percutaneous rotational atherectomy with proper rotablator (the size was 1-1.5 mm larger than the artery diameter) was performed in the arterial intima. After 4 weeks from percutaneous rotational atherectomy, arteriography was conducted to observe the changes in artery diameter. Then all dogs were sacrificed and the pathologic examination was conducted on the left and right axillary arteries. RESULTS: There were obvious changes with different degrees in 22 arteries, including 8 arteries with complete occlusion and 12 arteries with stenosis (≥2/3, 1/2, and 1/3 stenosis in 4, 4, and 4 arteries, respectively). The occlusion rate was 36.4% and the total effective rate was 90.9%. It was considered failure in other 2 arteries with <1/3 of stenosis. CONCLUSIONS: Percutaneous rotational atherectomy of arterial intima can promote the occlusion of arteries. This has provided a new choice for the treatment of PDA.

Severe cough and hemoptysis induced reopening of patent foramen ovale leading to significant decrease in pulmonary artery pressure in a patient with idiopathic pulmonary arterial hypertension： A case report.

Pulmonary arterial hypertension (PAH) is a perilous disease that precipitates right ventricular hypertrophy, induces right heart failure, and exerts deleterious ramifications on prognostic outcomes. The establishment of atrial communication can create a right-to-left shunt, thereby ameliorating hemodynamic parameters. Previous reports suggested that opening of a patent foramen ovale (PFO) was common in patients with severe PAH, but exhibited no discernible impact on long-term survival. We reported the case of a 39-year-old man with severe idiopathic PAH, who underwent reopening of the PFO due to severe cough and hemoptysis, followed by a marked amelioration in symptoms and a substantial decrease in pulmonary arterial pressure. The patient has survived for more than 12 years, persisting in World Health Organization functional class Ⅱ with mild PAH.

[Preliminary study on the efficacy and safety of oral sildenafil in pulmonary arterial hypertension in China].

OBJECTIVE: Sildenafil has been shown to be effective in pulmonary arterial hypertension (PAH). However, the impact of sildenafil on PAH has been under-investigated in China. The aim of the present study was to evaluate the efficacy and safety of oral sildenafil in PAH patients in China. METHODS: In this prospective, open-label and multi-center study, 90 patients were recruited from 14 centers to receive oral sildenafil (75 mg/d) for 12 weeks. They underwent a six-minute walk test (SMWT) and cardiac catheterization at the beginning and the end of 12 weeks. The primary endpoint was the changes in exercise capacity as assessed by SMWT. And the secondary endpoints included assessment of functional class, evaluation of cardiopulmonary hemodynamics and clinical deterioration (defined as death, transplantation and re-hospitalization for PAH). Drug safety and tolerability were also examined. RESULTS: There were 19 males and 71 females with an average age of 32.5 ± 12.1 years old (range: 18 - 61). Their etiologies were idiopathic (n = 15), related with congenital heart disease (n = 60), or related with connective tissue disease (n = 9) and chronic thromboembolic pulmonary hypertension (n = 6). Oral sildenafil significantly increased the SMWT distances [(342 ± 93) m vs. (403 ± 88) m, P < 0.001]. There was also remarkable improvement in Borg dyspnea score (2.9 ± 2.6 vs. 2.4 ± 2.0, P = 0.005). Furthermore, significant improvements in World Healthy Organization (WHO) functional class and cardiopulmonary hemodynamics were also found (mean pulmonary artery pressure, P < 0.001; cardiac index, P < 0.001; pulmonary vascular resistance, P < 0.001). Side effects were mild and consistent with other reports. CONCLUSION: This study confirms and extends previous studies. Oral sildenafil is both safe and effective for the treatment of adult PAH patients in China.

[Clinical analysis of transcatheter closure of atrial septal defects in elderly patients].

OBJECTIVE: To evaluate the clinical feature of patients with atrial septal defects (ASD) and the safety and efficacy of transcatheter closure of ASD in elderly patients. METHODS: Between May 2000 and June 2010, 82 patients aged (64.5 ± 3.8) years underwent attempted transcatheter ASD closure. Right heart catheterization was performed before intervention. Echocardiography was made at 1 day, 1, 3, 6 months after the procedure. The pre- and post-closure clinical feature, pulmonary artery pressure (PAP) and cardiac function were evaluated. RESULTS: In 82 patients, 37 (45.1%) patients were associated with pulmonary arterial hypertension (PAH). The systolic PAP and mean PAP [(44.1 ± 12.4) mm Hg (1 mm Hg = 0.133 kPa) and (25.2 ± 6.8) mm Hg, respectively] were measured by right heart catheterization before the procedure. One patient was unsuitable for closure because of severe PAH. The remaining 81 patients underwent successful ASD closure without major complications. After closuring, systolic PAP decreased from (52.7 ± 10.3) mm Hg to (31.8 ± 6.3) mm Hg (P < 0.05), and mean PAP descended from (30.9 ± 4.7) mm Hg to (21.8 ± 3.4) mm Hg (P < 0.05) in the 36 patients with PAH. The cardiac function improved post procedure. There were 6 new-onset atrial fibrillations during follow up. CONCLUSIONS: ASD in elderly patients are commonly associated with PAH. Transcatheter ASD closure is safe and effective in the majority of elderly patients.

[Effects of transcatheter closure of patent ductus arteriosus in 139 adult patients].

OBJECTIVE: To analyze the clinical feature and the effects of transcatheter closure of adult patients with patent ductus arteriosus (PDA). METHODS: Between January 2000 and April 2009, 139 patients [22 male, aged from 40 to 74: (49.8 +/- 6.8) years] with PDA were hospitalized in our hospital. Clinical data and effects of transcatheter closure of PDA were analyzed. RESULTS: There were 64 patients with NYHA classI, 53 with class II, 16 with class III and 6 with class IV before procedure. In 139 patients, pulmonary arterial hypertension (PAH) was found in 107 out of 139 patients (77.0%). Transcatheter PDA closure was not performed in 3 patients due to severe PAH and successfully performed in the remaining 136 patients (97.8%) without major complications. Post procedure aortic angiography evidenced minor residual shunt in 14 cases, small residual shunt in 2 cases and moderate shunt in 1 case. The NYHA class was significantly improved and the PAH significantly reduced [sPAP: (47.3 +/- 23.9) mm Hg (1 mm Hg = 0.133 kPa) vs. (28.1 +/- 12.3) mm Hg, P < 0.01] post procedure. CONCLUSION: PAH and heart failure were commonly associated with PDA in adult patients. Transcatheter PDA closure is safe and effective in these patients except those with severe PAH.

[Differences between adipose-derived stem cells and mesenchymal stem cells in differentiation into cardiomyocytes].

Adipose-derived stem cells (ASCs) are similar to bone marrow mesenchymal stem cells (MSCs) in growth kinetics, antigen expression and multi-lineage differentiation capacity. The present study was designed to investigate the differences between ASCs and MSCs in in vitro culture and differentiation into cardiomyocytes. ASCs were isolated from the fat tissue of New Zealand white rabbits while MSCs were obtained from rat bone marrow. Both ASCs and MSCs were cultured in Iscove's modified Dulbecco's medium supplemented with 15% fetal bovine serum in the same incubator and treated with various concentrations of 5-azacytidine. A clonogenic assay was used to quantify ASCs in fat tissue and MSCs in bone marrow. The number of ASCs in the fat tissue was much higher than that of MSCs in the bone marrow quantified by clonogenic assay, and MSCs showed a remarkably slower proliferative rate compared with ASCs, especially at primary passage. ASCs began to attach to the bottom of the culture flask 12 h after seeding. The cells in culture assumed a short spindle shape under a phase-contrast microscope and did not form clusters. The phenotype was maintained through repeated subcultures under nonstimulating conditions. No other cell phenotype was observed. MSCs attached to the culture flask at 24-48 h after seeding and grew in clusters. The cells were fibroblast-like and prone to senescence or differentiation into adipose cells. Both ASCs and MSCs before treatment with 5-azacytidine were stained positively for CD29, CD44 and CD105 but negatively for CD34 and CD45, α-sarcromeric actin, cardiac troponin T and von Willebrand factor. ASCs differentiated into cardiomyocytes only after treatment with 6-9 µmol/L of 5-azacytidine, while MSCs differentiated into cardiomyocytes with 3-15 µmol/L of 5-azacytidine. After treatment with ideal dose of 5-azacytidine, ASCs began to change their morphology and showed multinucleation within the first week and formed a ball-like appearance thereafter, while MSCs showed multinucleation at the second week and formed a stick-like appearance at 3-4 weeks. The percentage of ASCs differentiated into cardiomyocytes after treatment with 5-azacytidine was significantly higher than that of MSCs. The age of animal had no significant influence on the tissue content, proliferation and differentiation rate of ASCs. However, the tissue content of MSCs in bone marrow decreased with increased age of animal and MSCs from old donor rats exhibited less myogenic cells than those from the young rats after exposure to 5-azacytidine. These results indicate that ASCs have advantages over MSCs in tissue content, homology, growth and differentiation rate, suggesting that ASCs are more suitable for cellular cardiomyoplasty than MSCs.

[Interventional therapy for structural heart diseases in People's Liberation Army hospitals between 2005 and 2006].

OBJECTIVE: To evaluate the efficacy and safety of interventional therapy in structural heart diseases in 38 PLA hospitals. METHODS: Data including patient number underwent interventional therapy for structural heart disease, procedure details, immediate procedural complications were retrospectively collected in all the military hospitals between January 2005 and December 2006. RESULTS: Successful interventional therapy was achieved in 8692 out of 8862 patients (98.08%) with structural heart disease. Transcatheter closure of ventricular septal defect (VSD), atrial septal defect (ASD) and patent ductus arteriosus (PDA), and percutaneous balloon dilatation of mitral valve stenosis (MS) and pulmonary valve stenosis (PS) were the most performed procedures (97.99%). Up to 91.23% patients underwent transcatheter closure with domestic devices. The incidence of procedure-related complications was 4.33% (n = 384) which were most frequently associated with VSD closure. The commonest procedural complications included conduction blockades (n = 260), residue shunt (n = 42), device detachment (n = 30) and tricuspid incompetence (n = 22). Although the procedures performed in 2005 and 2006 increased 57.32% compared with those in 2003 and 2004, the success rate and the incidence of complications remained unchanged. CONCLUSION: Percutaneous treatment of structural heart disease is a safe and feasible alternative to surgery. Simulate complications arise long after the treatment, which suggests the importance of long-term follow-up for those patients who hare undergone interventional therapy.

Clinical outcomes of percutaneous or surgical closure of ruptured sinus of Valsalva aneurysm.

OBJECTIVE: To evaluate the clinical efficacy, safety, and long-term outcomes of percutaneous closure (PC) and surgical repair of ruptured sinus of Valsalva aneurysm (RSVA). METHODS: Eighty-five consecutive patients with RSVA were included in this study. Patients were considered candidates for PC if they met the criterion, surgical repair was performed on patients who were unsuitable or failed PC. Of them, 30 patients underwent PC, while the other 55 patients had surgical repair. RESULTS: RSVA was successfully occluded in 29 of 30 patients who were treated by PC. The mean narrowest diameter at the ruptured site was 6.45 ± 1.60 mm measured by aortography. One patient developed serious occluder-related aortic regurgitation and underwent surgery. The success rate of the interventional approach was 96.7%. In the surgical group, 23 patients underwent repair of combined RSVA and ventricular septal defect. The hospital mortality rate of the surgical approach was 3.57%. During a median follow-up of 83 months (8-152 months), the improvement in NYHA functional class in the PC group was significantly greater than those in the surgical group (P < .01). One patient died of infective endocarditis in the surgical group. There were no further serious complications. CONCLUSIONS: PC is a safe alternative to surgical repair for patients with isolated RSVA. Surgical repair is more suitable for those who have multiple cardiac lesions requiring surgical treatment or failed PC.

Transplantation of autologous adipose-derived stem cells ameliorates cardiac function in rabbits with myocardial infarction.

BACKGROUND: Adipose-derived stem cells (ADSCs) are capable of differentiating into cardiomyogenic and endothelial cells in vitro. We tested the hypothesis that transplantation of ADSCs into myocardial scar may regenerate infracted myocardium and restore cardiac function. METHODS: ADSCs were isolated from the fatty tissue of New Zealand white rabbits and cultured in Iscoves modified dulbeccos medium. Three weeks after ligation of left anterior descending coronary artery of rabbits, either a graft of untreated ADSCs (UASCs, n = 14), 5-azacytidine-pretreated ADSCs (AASCs, n = 13), or phosphate buffer saline (n = 13) were injected into the infarct region. Transmural scar size, cardiac function, and immunohistochemistry were performed 5 weeks after cell transplantation. RESULTS: ADSCs in culture demonstrated a fibroblast-like appearance and expressed CD29, CD44 and CD105. Five weeks after cell transplantation, transmural scar size in AASC-implanted hearts was smaller than that of the other hearts. Many ADSCs were differentiated into cardiomyocytes. The AASCs in the prescar appeared more myotube-like. AASCs in the middle of the scar and UASCs, in contrast, were poorly differentiated. Some ADSCs were differentiated into endothelial cells and participate in vessel-like structures formation. All the ADSC-implanted hearts had a greater capillary density in the infarct region than did the control hearts. Statistical analyses revealed significant improvement in left ventricular ejection fraction, myocardial performance index, end-diastolic pressure, and peak +dP/dt, in two groups of ADSC-implanted hearts relative to the control hearts. AASC-implanted hearts had higher peak -dP/dt values than did control, higher ejection fraction and peak +dP/dt values than did UASC-implanted hearts. CONCLUSIONS: ADSCs transplanted into the myocardial scar tissue formed cardiac islands and vessel-like structures, induced angiogenesis and improved cardiac function. 5-Azacytidine pretreatment before implantation is desirable for augmenting myogenesis. Transplantation of 5-azacytidine-treated ADSCs into the myocardial scar was more efficient than that of untreated ADSCs in preservation of cardiac function.