Assessing Pulmonary Arterial Hypertension in Infants With Severe Chronic Lung Disease of Infancy: A Role for a Pulmonary Artery Catheter?

The treatment of pulmonary arterial hypertension (PAH) associated with chronic lung disease of infancy (CLDI) is becoming commonplace. However, an optimal approach to the monitoring of this treatment has not been clearly established, and data suggest that such therapy may not be without risk. This study assessed the feasibility and safety of pulmonary artery catheter (PAC) placement and its role in the management of PAH associated with CLDI. The medical records of 12 infants with CLDI requiring chronic mechanical ventilation who underwent PAC monitoring were reviewed. Data analyzed included demographics, hemodynamic data, PAH pharmacological therapy, respiratory support, echocardiographic data, sedation level, complications related to PAC use, and mortality. In this analysis, PAC placement and monitoring was found to be feasible, appeared safe, and was associated with the ability to wean inspired oxygen, decrease sedation, and titrate PAH therapy without untoward effect. However, no definitive conclusions can be drawn from this report given its small sample size and uncontrolled, retrospective design. It is hoped that these data will renew interest in PAC monitoring for CLDI and foster prospective study where its true value can be ascertained.     

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??Objective To evaluate the effect of plugging tests in the diagnosis and interventional treatment of pediatric patients with patent duct arteriosus complicated with severe pulmonary hypertension ??PAH??. Methods??All the clinical data of 5 patients of PDA with severe PAH were retrospectively reviewed??including the heart catheterization data??the relevant parameters before and after acute pulmonary vasodilator tests and the changes of Pp??Ps??PVRI??and aortic blood oxygen saturation before and after the plugging tests. Results??Only 1 patient was with dynamic PAH according to heart catheterization test??however??for the other 4 patients it was difficult to judge the property of PAH. Acute pulmonary vasodilator tests were performed in 5 patients and 4 were diagnosed with dynamic PAH. Plugging tests were conducted in 5 patients and all of them were diagnosed with dynamic PAH. All the patients underwent interventional therapy well and the follow-up results were good. Conclusion??For PDA patients with severe PAH??plugging test diagnosis can be made on the properties of the PAH and if the determination is dynamic??the intervention treatment can be completed at the same time. This method can effectively avoid the limitations of cardiac catheterization and acute pulmonary vasodilator testing evaluation of PAH properties.     

Connective Tissue Disease Presenting With Signs and Symptoms of Pulmonary Hypertension in Children

Our case series describes three children who were initially diagnosed as having severe pulmonary arterial hypertension (PAH) and subsequently found to be positive for specific autoantibodies suggestive of an underlying autoimmune process. The signs and symptoms of PAH are subtle and may be part of the initial presentation of childhood connective tissue disease (CTD). Evaluation for connective tissue disease in the newly diagnosed pulmonary hypertension (PH) patient is important because early diagnosis of PH as well as CTD is crucial in the successful management of these complex patients. Ongoing monitoring for CTD in patients with severe PAH is warranted.     

Mucoviscidosis and precapillary pulmonary hypertension

Various pathomechanisms are responsible for the development of pulmonary arterial hypertension (PAH) in cystic fibrosis (CF). Main factors are chronic hypoxia and the loss of peripheral vessels caused by recurrent infectious lung disease and lung fibrosis. Measurement of pulmonary artery pressure and pulmonary resistance provide reliable information on PAH. Many non invasive procedures, including echocardiography, myocardial and pulmonary imaging by radionuclide, proved to be not sensitive enough to diagnose PAH. Arterialized pO2 (taken from the hyperemized ear lobe), however, measured during standardized submaximum work load, seems to be a valuable parameter to estimate PAH (r = 0.92). Treatment of PAH in CF-patients is, at the moment, predominantly based on the improvement of the general therapeutical regimen of CF and on long-term oxygen insufflation, which should be initiated as soon as there are first signs of PAH.     

Pulmonary arterial hypertension in children: A Medical Update

Pulmonary arterial hypertension (PAH) is a life-threatening disease characterized by a progressive pulmonary vasculopathy with ensuing right heart failure if left untreated. In the 1980’s, prior to the current treatment era, idiopathic pulmonary arterial hypertension (IPAH) carried a poor prognosis with a 10 month median survival for children after diagnosis. However, in 1995 continuous intravenous epoprostenol was approved for the treatment of severe PAH, improving hemodynamics, quality of life, exercise capacity, functional class and survival. In the past decade there have been further advances in the treatment of PAH; however, there is still no cure. While much of the groundbreaking clinical research has been performed in adults, children have also seen the benefits of PAH novel therapies. The target population among pediatric patients is expanding with the recent recognition of pulmonary hypertension as a risk factor for sickle cell disease patients. With rapid advances, navigating the literature becomes challenging. A comprehensive review of the most recent literature over the past year on available and emerging novel therapies as well as an approach to target pediatric populations provides insights into the management of pediatric PAH patients.     

Acute Pulmonary Vasodilator Testing With Inhaled Treprostinil in Children With Pulmonary Arterial Hypertension

Acute pulmonary vasodilator testing (AVT) is essential to determining the initial therapy for children with pulmonary arterial hypertension (PAH). This study aimed to report the initial experience with inhaled treprostinil used for AVT in children with PAH and to evaluate the hemodynamic change after inhaled treprostinil compared with inhaled nitric oxide. This prospective cohort study was designed for 13 children who underwent AVT with inhaled treprostinil or oxygen plus inhaled nitric oxide (iNO) during catheterization. Inhaled treprostinil was delivered during cardiac catheterization by adapting the Optineb ultrasonic nebulizer via either a flow-inflating bag or the manual mode of the anesthesia system. The median age of the patients was 10 years (range 4–17 years). The etiologies of PAH included idiopathic PAH and associated PAH. All the patients tolerated inhaled treprostinil without marked clinical worsening and received six or nine breaths (36 or 54 μg) of treprostinil. The median of the total treprostinil doses was 1.53 μg/kg (range 0.71–2.89 μg/kg). Inhaled treprostinil was administrated via an endotracheal tube (n = 8), anesthesia mask (n = 3), or laryngeal mask airway (n = 2). Inhaled nitric oxide (iNO) and inhaled treprostinil significantly decreased the mean pulmonary artery pressure and the pulmonary vascular resistance index compared with baseline. Three adverse events were reported after inhaled treprostinil, including cough and mild to moderate hypotension with higher doses. All adverse events resolved without any intervention. This study report is the first to describe the use of inhaled treprostinil for AVT in children with PAH. In this small pediatric cohort, inhaled treprostinil was effectively delivered and well tolerated and may be useful for AVT.     

Pulmonary arterial hypertension in children: A Medical Update

Pulmonary arterial hypertension (PAH) is a life-threatening disease characterized by a progressive pulmonary vasculopathy with ensuing right heart failure if left untreated. In the 1980’s, prior to the current treatment era, idiopathic pulmonary arterial hypertension (IPAH) carried a poor prognosis with a 10 month median survival for children after diagnosis. However, in 1995 continuous intravenous epoprostenol was approved for the treatment of severe PAH, improving hemodynamics, quality of life, exercise capacity, functional class and survival. In the past decade there have been further advances in the treatment of PAH; however, there is still no cure. While much of the groundbreaking clinical research has been performed in adults, children have also seen the benefits of PAH novel therapies. The target population among pediatric patients is expanding with the recent recognition of pulmonary hypertension as a risk factor for sickle cell disease patients. With rapid advances, navigating the literature becomes challenging. A comprehensive review of the most recent literature over the past year on available and emerging novel therapies as well as an approach to target pediatric populations provides insights into the management of pediatric PAH patients.     

Weaning of epoprostenol in a small infant receiving concomitant bosentan for severe pulmonary arterial hypertension secondary to bronchopulmonary dysplasia

Endothelin receptor antagonism is an important therapeutic tool of pulmonary arterial hypertension (PAH). Bosentan was the first orally active, dual antagonist of endothelin receptors in human adults, and has been recently considered for children as well. However, little is known about bosentan treatment in children weighing less than 10 kg. We describe the use of bosentan concomitantly to epoprostenol in an infant weighing 3.5 kg and affected with severe bronchopulmonary dysplasia (BPD) and PAH. At 5 months old, when she presented subsystemic PAH secondary to severe BPD, she was treated with oxygen, digoxin and diuretics. At 8 months old, due to severe PAH not responsive to 100% oxygen, high frequency oscillatory ventilation (HFOV) and nitric oxide (NO), we started epoprostenol and bosentan. Bosentan dose was doubled at 9 months old, when HFOV and NO were slowly discontinued due to improved oxygenation index. Regular echocardiographic measurements of systolic right ventricular pressure were recorded by the method of tricuspidal atrio-ventricular gradient. A four-month combined epoprostenol and bosentan treatment decreased systolic right ventricular pressure from 68% to 40% of the systemic level, till its normalization at 11 months old. Later, when bosentan and epoprostenol were discontinued and sildenafil was started, severe PAH was reported again. Our patient died due to septic shock and refractory hypoxia at 14 months old.     

Fatal pulmonary arterial hypertension in an infant girl with incontinentia pigmenti

We report the case of an infant girl with incontinentia pigmenti (IP) complicated by fatal pulmonary arterial hypertension (PAH). She was diagnosed with IP, based on the presence of specific skin lesions, neonatal seizures, hypereosinophilia and a maternal family history of IP. At the age of 2 months, she was diagnosed with PAH on systolic heart murmur due to tricuspid valve regurgitation. Despite several treatments for PAH but not including epoprostenol, severe PAH persisted and she died of pulmonary hypertensive crisis at the age of 5 months. On postmortem histopathology the pulmonary artery had severe intimal thickening, with occlusion or stenosis of the vascular lumen of the small pulmonary arteries as well as partial plexiform lesions, all of which were compatible with PAH. Modulation of nuclear factor‐κB signaling may be involved in the development of PAH in IP.     

Experience with long-term nifedipine therapy in paediatric cardiological patients

Clinical experience with long-term nifedipine treatment in 23 patients aged between 1 1/12 and 14 8/12 years is reported. The cardiopulmonary diseases comprised primary pulmonary diseases with pulmonary hypertension (n = 4), congenital heart defects with intracardiac shunts and pulmonary hypertension which either were inoperable as a result of an Eisenmenger reaction (n = 7) or presented a high surgical risk (n = 5), or defects in which pulmonary hypertension did not regress despite corrective (n = 1) or palliative surgery (n = 3), and congenital defects without pulmonary hypertension (n = 3). Subjective improvement with an increase in physical performance was clearly observed in 15 cases. Echocardiography and cardiac catheter examinations showed no progression of the pulmonary arterial diseases, except in 1 patient with severe primary pulmonary hypertension and an 11-year observation period with nifedipine treatment during the last 4 years. No complications occurred during the 4 corrective operations. A patient aged 14 8/12 years with the Down syndrome and atrioventricular septal defect developed easily controllable heart failure during 7-day administration of nifedipine without additional cardiotherapy. 4 children initially suffered from flushed face and scalp, in one case with headache; 2 children reported fatigue. Long-term treatment with nifedipine should begin with strict 7-day supervision in hospital and possibly additional digitalization. Success of the treatment was determined by an improved quality of life in patients with primary pulmonary hypertension and inoperable defects, and by a reduced perioperative risk and postoperative regression of pulmonary hypertension in patients with operable defects.     

Clinical Manifestations and Long-Term Follow-Up in Pediatric Patients Living at Altitude With Isolated Pulmonary Artery of Ductal Origin

This study's aim was to define the clinical manifestations and long-term outcome of pediatric patients living at altitude with isolated pulmonary artery (PA) of ductal origin (IPADO). This was a retrospective cohort study of 17 consecutive cases of IPADO at a single center. All patients lived at modest altitude (median 2050 m [range 1700 m to 3050 m]). Fifteen children (88%) were symptomatic at presentation. High-altitude pulmonary edema was present in 2 patients (12%) at diagnosis, and only 1 patient had episodes of hemoptysis during follow-up. Fourteen patients (82%) demonstrated evidence of pulmonary arterial hypertension (PAH). Among 14 patients with PAH, 11 patients had surgical interventions. PAH resolved in 5 of 11 patients (45%) undergoing surgical rehabilitation. One patient died during follow-up, and 7 patients are receiving oral vasodilator therapies due to residual PAH; 14 patients remained asymptomatic. Our study showed that early intervention in patients with IPADO at modest altitude can potentially rehabilitate the isolated PA and reverse PAH. Whether surgery is indicated for patients with this disorder in the absence of PAH is unknown.     

Pulmonary hypertension in a case of Hb-Mainz hemolytic anemia

The development of pulmonary arterial hypertension (PAH) is the leading cause of mortality in patients with thalassemia and sickle cell anemia and was reported to occur in hemolytic anemias such as hereditary stomatocytosis, and paroxysmal nocturnal hemoglobinuria. Here, we report for the first time on the development of PAH in a patient with Hb-Mainz hemolytic anemia. Hb-Mainz is an unstable hemoglobin variant resulting from mutations at codon 98 of the beta chain gene (Val>Glu) characterized by severe chronic hemolytic anemia. The development of PAH in this patient further supports the contention that there is a clinical syndrome of hemolysis-associated development of PAH.     

Pulmonary arterial hypertension in children: Diagnostic work-up and challenges

The diagnostic evaluation of a pediatric patient with suspected pulmonary arterial hypertension (PAH) is extensive but essential, given the rapid progression of the disease if left undiagnosed and untreated. The major goals of performing a complete diagnostic work-up are to confirm the diagnosis of PAH, assess disease severity, rule out associated diseases, and begin to formulate an individualized treatment plan for the pediatric patient with pulmonary hypertension. This article will provide a comprehensive review of the diagnostic work-up of the child with suspected PAH as well as a review of some of the challenges faced when assessing a child for PAH.     

Safety experience with bosentan in 146 children 2-11 years old with pulmonary arterial hypertension: results from the European Postmarketing Surveillance program

The oral dual endothelin receptor antagonist bosentan has been shown to improve the short- and medium-term course of adult pulmonary arterial hypertension (PAH); however, data from clinical studies in children are limited. This analysis investigated the safety profile of bosentan in pediatric patients in a European, prospective, noninterventional, Internet-based postmarketing surveillance database (Tracleer PMS). Pediatric patients (aged 2-11 y) were compared with patients aged > or =12 y. Over a 30-mo period, 4994 patients, including 146 bosentan-na?ve pediatric patients (51.4% males), were captured in the database. Predominant etiologies in children were idiopathic PAH (40.4%) and PAH related to congenital heart disease (45.2%). The majority of children were in New York Heart Association functional class II (28.1%) or III (50.7%), and median exposure to bosentan was 29.1 wk. Elevated aminotransferases were reported in 2.7% of children versus 7.8% of patients > or =12 y. The discontinuation rate was 14.4% in children versus 28.1% in patients > or =12 y. The Tracleer PMS results provide unique information on pediatric PAH in Europe. They also suggest that Tracleer may be better tolerated in children than in adults. This observation confirms the value of monthly monitoring of liver function for the duration of bosentan treatment.     

Pulmonary arterial hypertension associated with chronic active Epstein–Barr virus infection

Chronic active Epstein–Barr virus (EBV) infection (CAEBV), characterized by persistent infectious mononucleosis‐like symptoms, can lead to cardiovascular complications including coronary artery aneurysm or myocarditis. Here, we present the case of an 11‐year‐old boy with pulmonary arterial hypertension (PAH) and junctional ectopic tachycardia associated with CAEBV. The patient did not have any major symptoms attributed to CAEBV, such as fever, lymphadenopathy or splenomegaly when the PAH developed. Mild liver dysfunction was found at the first examination, and it persisted. Two years after the PAH symptoms appeared, CAEBV was evident, based on deteriorated liver function, hepatosplenomegaly, and coronary artery aneurysms. CAEBV should be considered as a cause of secondary PAH, particularly when liver dysfunction coexists.     

Complications of cerebrospinal fluid shunts

In the period 1972–81, 572 hydrocephalic children were treated using the Upadhyaya shunt valve, One hundred and seventys-even of these patients needed a total of 350 shunt revisions. Indications for revisions were; shunt blockage 245 (70% of total revisions) shunt infections 40 (11.5%) catheter disconnections/fractures 19 (5.5%) and intvacranial hemorrhage 9 (2.5%). Intracranial bleeds were more commonly seen in hydrocephalus associated with tuberculous meningitis and were invariably fatal. Infrequent complications were CSF leak, shunt extrusion, valve incompetence, pulmonary hypertension and pleural effusion. Thirty-nine patients died. Overall results of the Upadhyayay shunt valve compare favourably with other reported series.     

儿童先天性心脏病血清Apelin水平与肺动脉压关系的初步探讨

目的 初步探讨先天性心脏病患儿血清Apelin 水平与肺动脉压的关系.方法 手术治疗的先心病患儿126 例,检测患儿术前及术后第7 天的血清Apelin 水平.建立体外循环前检测并计算肺动脉收缩压/体循环收缩压(Pp/Ps)的比值,依据Pp/Ps 分组:无肺动脉高组压(PAH)组、轻度PAH 组、中度PAH 组和重度PAH 组;术后第7 天超声心动图估测肺动脉平均压(PAMP).结果 无PAH,以及轻、中、重度PAH 各组术前及术后的血清Apelin 水平依次降低,差异有统计学意义(PPr=-0.51,-0.54,P结论 先心病患儿并发肺动脉高压及其发展与血清Apelin 水平降低有关系,血清Apelin 对诊断先心病患儿是否并发肺动脉高压及其程度的意义值得深入研究.     

儿童肺动脉高压的药物治疗进展

本文综述了儿童肺动脉高压（PAH）的药物治疗现状,并简要介绍了新的治疗靶点。前列环素类似物、内皮素受体拮抗剂及磷酸二酯酶 5抑制剂等3类药物能显著改善PAH患儿的血流动力学、运动耐量并延长生存。随着这些药物在儿科的逐步应用,儿童PAH的治疗取得了明显进步,但仍需开展进一步的大样本随机对照试验,同时还必须努力研发新型药物。     

Management of pulmonary hypertension in Down syndrome

Children with Down syndrome (DS) are at greater risk of pulmonary arterial hypertension (PAH) than the general population, partly due to upper airway obstruction and congenital heart disease. We wished to review our management of PAH and suggest a protocol for the systematic management of these children. Children with DS and PAH were included as referred for assessment from March 2005 to May 2010. Twenty-five patients (13 boys) met inclusion criteria. The median age was 385 days (range, 106 to 5,734); mean tricuspid regurgitation jet was 3.5 (range, 2.7–4.8) m/s. At cardiac catheterisation, mean pulmonary artery mean pressure was 26 mmHg (range, 12 to 46), and mean pulmonary vascular resistance (PVR) was 4.14 U.m² (range, 1.20 to 12.43) at baseline. PVR fell to a mean of 2.68 U.m² (range, 0.38 to10.69) with 20 ppm inhaled nitric oxide and 100% oxygen. Respiratory assessment included polysomnography (18), bronchoscopy (16), showing malacia (eight), adenotonsillar hypertrophy (eight) and floppy aryepiglottic folds (four). One lung biopsy showed plexogenic arteriopathy, and one was diagnosed with tracheo-oesophageal fistula. Conclusion: In order to manage this complex group of patients, a combined cardiological, respiratory and surgical approach was required. A protocol with cardiac catheterisation, blood tests and respiratory assessment is suggested for the management of pulmonary hypertension in these children.     

Regression of Pulmonary Vascular Disease After Therapy of Abernethy Malformation in Visceral Heterotaxy

A 1-year-old boy who had left isomerism and corrected transposition of the great arteries (c-TGA) with moderate-sized ventricular septal defect, severe pulmonary artery hypertension (PAH), and pulmonary vascular disease with significant right-to-left shunting received a diagnosis of type 2 Abernethy malformation, which was partly responsible for disproportionate PAH in the child. The malformation was treated by plugging of the portosystemic shunt. Follow-up cardiac catheterization on sildenafil demonstrated significant left-to-right shunting (2.16:1) and a fall in pulmonary vascular resistance, making surgical correction possible. This case highlights the importance of searching for additional rare causes of PAH in patients with congenital heart diseases when the degree of pulmonary hypertension is disproportional to the defect size.