波生坦治疗儿童肺动脉高压的研究进展

波生坦是一种非选择性的内皮素受体拮抗剂,在儿童肺动脉高压的治疗中具有重要作用。波生坦能改善肺动脉高压儿童的运动耐量、降低肺血管阻力、改善心功能,且不良反应较成人更少。与其他药物联用能改善患儿的生活质量。波生坦的远期效果、最佳治疗时程及药物联合应用仍有待于进一步研究。     

室间隔缺损并肺动脉高压的围术期治疗

目的总结小儿室间隔缺损(VSD)并肺动脉高压(PH)的围术期治疗经验。方法回顾性分析1995年4月~2004年10月18例VSD并PH患儿一般临床资料。术前1周静滴极化液、吸氧、人血丙种球蛋白提高患儿抵抗力,10例患儿用前列腺素E1(PGE1)。手术在体外循环下中度低温下矫治心内畸形。术后给予多巴胺、多巴酚丁胺3~10μg/(kg·min),硝酸甘油1~5μg(kg·min)。结果术后出院前腺动脉收缩压/主动脉收缩压比值(PP/PS)0.39±0.09与术前比较明显下降,平均动脉压(MPAP)较术前明显下降(P<0.05)。除1例死于低排综合征。余均治愈出院。结论完善的围术期治疗能使VSD并PH小儿取得良好效果。     

Sildenafil for the Treatment of Pulmonary Hypertension in Pediatric Patients

Sildenafil is a phosphodiesterase 5 inhibitor widely used for the treatment of pulmonary hypertension in children. Despite limited available safety and efficacy evidence, use of sildenafil continues to increase. To date, sildenafil use for pediatric pulmonary hypertension has been characterized for 193 children through 16 studies and 28 case series and reports. The primary efficacy data suggest that sildenafil is beneficial for facilitating the weaning of inhaled nitric oxide in children after cardiac surgery. Compiled safety data suggest that sildenafil is well tolerated among children with idiopathic pulmonary arterial hypertension and pulmonary arterial hypertension associated with congenital heart disease. This review summarizes the available data describing the use, safety, and efficacy of sildenafil for children with pulmonary hypertension.     

Morbidity and Mortality in Iranian Children with Juvenile Systemic Lupus erythematosus

Objective: Juvenile systemic lupus erythematosus (JSLE) is a common rheumatologic disorder that involves multi organ systems. Prognosis of lupus in children may be poorer than in adults. In this study, we determined mortality and morbidity rates in the pediatric SLE in Iran. Methods: In a cross sectional study, we evaluated 120 children with SLE who had registered in our pediatric rheumatology database within 2004-2010. Data including sex, age, remission, age at the time of diagnosis, age at the time of study, various types of organ involvement, mortality and remission were extracted from this database. Findings : From 120 cases, 77% (92 cases) were females and 23% (28 cases) males (F:M=3.3). Mean follow up period was 56±32 months and mean age at the time of manifesting disease 10.34±2.9 years. Mortality rate was 10% (12 cases) in our investigation. Musculoskeletal involvement showed significant difference between various age groups (P<0.01), that was more frequent in group of 7 years and older. Frequency of oral ulcer and ophthalmic involvement in boys was significantly higher than in girls (P<0.05). Frequency of cardiovascular involvement (P<0.01) and renal involvement (P<0.01) was significantly higher in the patients who had no remission. There was a significant association between mortality rate and cardiac (P<0.02, OR=4.9), pulmonary (P<0.01, OR=10.167) and liver (P<0.05, OR=1.19) involvement. Conclusion: In our investigation 1-year survival rate was 97% and 5-year survival rate 89%. Liver, cardiac and pulmonary involvements have an association with higher mortality in JSLE patients.Key Words: Systemic Lupus Erythematosus, Mortality, Morbidity, Juvenile, Children, Iran     

Treatment of Pulmonary Hypertension in Children with Chronic Lung Disease with Newer Oral Therapies

Chronic lung disease (CLD) is often complicated by chronic pulmonary vascular changes and pulmonary hypertension (PH) in young children. Current therapies for severe PH in such patients, including oxygen, inhaled nitric oxide, and parenteral prostacyclin, are often suboptimal, cumbersome, and expensive. Recently, oral endothelin receptor blockers and phosphodiesterase-5 inhibitors have been used successfully to control and reverse pulmonary vascular disease in idiopathic PH, but the use and efficacy of these agents in pediatric CLD have not been previously reported. We report a series of six children with CLD and severe PH treated with bosentan (six of six) and sildenafil (four of six). Vascular reactivity was assessed by cardiac catheterization prior to and after 6 months of therapy. Serial echocardiography was also used to assess response. Patients have been treated for 2.1–2.9 years (mean, 2.53 years). Response to therapy has included improvement in oxygenation, symptoms, echocardiographic parameters, and hemodynamics by cardiac catheterization. Transiently elevated liver enzymes were noted associated with viral respiratory infections in two subjects; no other adverse effects were noted. Three patients with large cardiac right-to-left shunts prior to therapy had subsequent shunt reversal, two of whom underwent shunt closure later. Oral therapy with bosentan alone or in combination with sildenafil improves PH in patients with CLD over a period of 3–4 years.     

Exercise Testing in Children with Primary Pulmonary Hypertension

Cardiopulmonary exercise testing is a useful noninvasive tool to assess physiological changes associated with exercise. Developing noninvasive methods to assess the severity of cardiopulmonary disorders, as well as the response to therapeutic interventions, is useful in conditions, such as primary pulmonary hypertension, in which invasive procedures carry significant risks. The 6-minute walk test is a simple measure of exercise endurance. Exercise studies that measure both hemodynamic and ventilatory responses provide additional information regarding the interaction of the circulatory and pulmonary systems. Subtle changes in exercise capacity may suggest deterioration prior to clinical manifestations. This may lead to an earlier reevaluation, including repeat cardiac catheterization, and subsequently changes in medical and/or surgical therapy.     

Pulmonary Hypertension in Children and Adolescents with Sickle Cell Disease

The prevalence of pulmonary hypertension (PHTN) in the pediatric sickle cell disease (SCD) population is not known despite its high prevalence in adult patients. Our hypothesis was that increased pulmonary artery pressures (PAPs) would be found in SCD children and adolescents, especially those with a history of pulmonary complications: acute chest syndrome, obstructive sleep apnea, asthma, and reactive airway disease. Fifty-two SCD children, 23 of whom had underlying pulmonary disease, were screened for PHTN, which was defined as a tricuspid regurgitant jet velocity (TRV) of at least 2.5 m/s. Twenty-four (46.15%) SCD patients had increased PAP (i.e., TRV ≥2.5 m/s), and 6 (11.5%) had significant PHTN (i.e., TRV ≥3.0 m/s). Pulmonary disease was marginally associated with PHTN (odds ratio 2.80 and confidence interval 0.88 to 8.86; p = 0.0795). As in adult SCD patients with PHTN, this complication was correlated with the degree of hemolysis as manifested by significantly higher lactate dehydrogenase and bilirubin, lower hemoglobin and hematocrit levels, and a strong association with Hb-SS phenotype. However, after statistical adjustment for age and sex, increased serum LDH was not associated with the development of PHTN. Further studies are needed to clarify the prevalence and mechanisms of PHTN in pediatric and adolescent patients with SCD.     

Parvovirus B19 Myocarditis Causes Significant Morbidity and Mortality in Children

Although parvovirus B19 (PVB19) currently is the most common cause of viral myocarditis, limited pediatric data exist. Whereas other viruses infect cardiomyocytes, PVB19 targets coronary endothelium, leading to myocardial ischemia and dysfunction. A retrospective review investigated patients with polymerase chain reaction (PCR)-verified PVB19 myocarditis at Texas Children’s Hospital and Arkansas Children’s Hospital (January 2005 to August 2008). The primary end points of the study were transplant-free survival and circulatory collapse (death, mechanical support, or transplantation). For the 19 patients identified (age, 6 months to 15 years), the most common presenting symptoms were respiratory and gastrointestinal. At admission, all the patients demonstrated ventricular dysfunction requiring inotropic support (median ejection fraction, 24 %; median left ventricle end-diastolic diameter [LVEDD] z-score, 4.6). Whereas T-wave abnormalities were common, ST elevation was evident in five patients (two died and three required transplantation). Serum B-type natrietic peptide was elevated in all 12 patients tested (range, 348–8,058 pg/ml), and troponin I was high in 7 of 9 patients (range, 0.04–14.5 ng/ml). Of the 15 patients with circulatory collapse, nine received mechanical support, eight underwent successful transplantation, and five died. Only six patients (32 %) experienced transplant-free survival, and five patients had full recovery of function at discharge. In the transplant-free survival group, ST changes on presenting electrocardiography were less likely (p = 0.03), and the admission LVEDD z-score tended to be lower (3.3 vs 5.6; p = 0.08). In children, PVB19 myocarditis causes significant mortality and morbidity. Although mechanical intervention can support patients in the initial stage of decompensated heart failure, patients with PVB19 myocarditis often demonstrate persistent dysfunction requiring medical therapy and transplantation.     

Potts Anastomosis for Children with Idiopathic Pulmonary Hypertension

Mortality in children with idiopathic pulmonary arterial hypertension is high, emphasizing the need for novel therapeutic approaches. A surgical approach consisting in the creation of anastomosis between descending aorta and left pulmonary artery, the Potts shunt, has been proposed to decompress right ventricle. We reported two cases of severe idiopathic pulmonary hypertension in children with right heart failure refractory to medical treatment who benefited of Potts shunt.     

Nitric Oxide-Associated Pulmonary Edema in Children With Pulmonary Venous Hypertension

Nitric oxide (NO)-associated pulmonary edema is rarely reported in children; in adults, it is often associated with left-sided heart failure. We report a case series of children with NO-associated pulmonary edema, which was defined as new multilobar alveolar infiltrates and worsening hypoxemia within 24 h of initiation or escalation of NO and radiologic or clinical improvement after NO discontinuation. We identified six patients (0.4–4 years old) with ten episodes of NO-associated pulmonary edema. Diagnoses included atrioventricular canal defect with mitral valve disease (n = 2), pulmonary atresia and major aorta-pulmonary collateral arteries (n = 2), total anomalous pulmonary venous return (n = 1), and pulmonary veno-occlusive disease (n = 1). All patients had evidence of pulmonary venous hypertension, and two had mitral valve disease resulting in clinical evidence of left-sided heart failure. Pulmonary edema improved or resolved within 24 h of discontinuing NO. At cardiac catheterization, mean left atrial pressure was <15 mmHg in three of three patients (none with mitral valve disease), whereas pulmonary artery occlusion pressure was >15 mmHg in two of five patients. In conclusion, we describe six young children with NO-associated pulmonary edema and pulmonary venous hypertension. Only two of these children had left-sided heart failure: Left atrial pressure as well as pulmonary artery occlusion pressure may not be helpful in identifying children at risk for NO-associated pulmonary edema.     

Initial Experience With Tadalafil in Pediatric Pulmonary Arterial Hypertension

This study aimed to investigate the safety, tolerability, and effects of tadalafil on children with pulmonary arterial hypertension (PAH) after transition from sildenafil or after tadalafil received as initial therapy. A total of 33 pediatric patients with PAH were retrospectively evaluated. Of the 33 patients, 29 were switched from sildenafil to tadalafil. The main reason for the change from sildenafil was once-daily dosing. The average dose of sildenafil was 3.4 ± 1.1 mg/kg/day, and that of tadalafil was 1.0 ± 0.4 mg/kg/day. For 14 of the 29 patients undergoing repeat catheterization, statistically significant improvements were observed after transition from sildenafil to tadalafil in terms of mean pulmonary arterial pressure (53.2 ± 18.3 vs. 47.4 ± 13.7 mmHg; p < 0.05) and pulmonary vascular resistance index (12.2 ± 7.0 vs 10.6 ± 7.2 Units/m(2); p < 0.05). Clinical improvement was noted for four patients treated with tadalafil as initial therapy. The side effect profiles were similar for the patients who had transitioned from sildenafil to tadalafil including headache, nausea, myalgia, nasal congestion, flushing, and allergic reaction. Two patients discontinued tadalafil due to migraine or allergic reaction. One patient receiving sildenafil had no breakthrough syncope after transition to tadalafil. Tadalafil can be safely used for pediatric patients with PAH and may prevent disease progression.     

Vasodilator Testing with Nitric Oxide and/or Oxygen in Pediatric Pulmonary Hypertension

The objective of this study was to determine whether a combination of inhaled nitric oxide (iNO) and O₂ is more effective than 100% O₂ or iNO alone for acute vasodilator testing in children. An open, prospective, randomized, controlled trial was conducted at 16 centers. Subjects were children 4 weeks to 18 years of age with pulmonary hypertension (PH) and increased pulmonary vascular resistance (PVR) undergoing right heart catheterization for acute vasodilator testing. All patients were tested with each of three agents (80 ppm iNO, 100% O₂, combination of 80 ppm iNO/100% O₂) in three 10-min treatment periods, and hemodynamic measurements obtained. Primary outcome measures were percentages of acute responders with O₂ alone vs. iNO/O₂ and iNO alone vs. iNO/O₂. More patients on the combination were acute responders compared with O₂ or iNO alone (26% vs. 14%, P = 0.019, and 27% vs. 24%, P = 0.602, respectively). Changes in PVR index and mean pulmonary arterial pressure vs. baseline were greater with iNO/O₂ vs. either O₂ or iNO alone (P < 0.001). Survival at 1-year follow-up included (1) 90.9% of acute responders to the combination, compared with 77.8% of nonresponders to the combination, and (2) 85.7% of acute responders to O₂ alone, compared with 80.6% of nonresponders to O₂. Key conclusions are as follows. In children with PH and increased PVR, more acute responders were identified with the iNO/O₂ combination vs. O₂ alone. While there was no significant difference in acute responder rate with iNO alone vs. iNO/O₂, the combination improved pulmonary hemodynamics acutely better than iNO alone. One-year survival data show similar rates between the iNO/O₂ and the O₂ alone groups; however, the combination may be more effective than O₂ alone in discriminating survivors versus nonsurvivors at long-term follow-up.     

高原肺动脉高压190例

目的研究高原肺动脉高压(PH)的临床特点,提高临床诊断的准确性。方法借鉴循证医学系统评价方法,对四川大学华西第二医院儿科1996~2005年出院诊断为高原PH的住院病例资料及通过中国期刊全文数据库检索的1994~2005年国内文献报告临床病例资料进行综合分析。结果共收集190例病例资料,其中17例来自四川大学第二医院儿科病历记录,173例来自国内文献报告。该病主要发生于移居高原的1岁以内小儿,男童较多见,种族差别明显。主要症状有呼吸困难发绀、咳嗽和充血性心力衰竭等;主要体征有右心衰和PH。结论高原PH临床表现复杂多样,超声心动图对该病诊断很有帮助,需加强认识,以提高临床诊断水平。     

原发性肺动脉高压的诊断和治疗

目的探讨儿童原发性肺动脉高压(PPH)的临床诊治特点。方法对收治15例PPH患儿的临床资料及治疗、转归进行分析。结果15例均有不同程度心功能不全症状、体征,心电图示右室肥厚,超声心动图示右房、右室大、肺动脉增宽。14例行心导管检查显示肺动脉压增高、肺小动脉楔压正常。PPH预后差,仅3例治疗后活动耐力增加。结论PPH症状无特异性,心导管检查在诊断中具有重要作用。PPH缺乏有效治疗,血管扩张剂和钙通道阻滞剂有一定疗效。