Pulmonary veno-occlusive disease: a misnomer?

Pulmonary veno-occlusive disease (PVOD) is a rare entity with non-specific signs and symptoms and is nearly always associated with a dismal prognosis. This review will first consider pulmonary hypertension in general and then will focus on PVOD specifically with particular attention to the pathophysiology of the disease. Classically PVOD is described as a disease primarily involving obstructed venules, with the arterial side of the circulation involved to a lesser degree. This article discusses the demographics of affected individuals; the ways in which an accurate diagnosis can be made, including imaging features; predisposing diseases and associated disorders; and potential treatment.     

Left Innominate Vein–Pulmonary Artery Shunt with Glenn Anastomosis in a Fontan Candidate with Central Pulmonary Artery Stenosis

Heart failure developed 9 years after Fontan takedown with systemic–pulmonary artery shunt in a 12-year-old girl with pulmonary atresia, intact ventricular septum, and obstruction in the proximal pulmonary artery. Surgical scar after multiple operations complicated direct repair of the pulmonary artery, and thus she was not eligible for definitive palliation. Left innominate vein–to–left pulmonary artery shunt using an expanded polytetrafluoroethylene conduit in association with Glenn anastomosis functionally established an unobstructive superior cavopulmonary connection without direct repair of the central pulmonary artery, later facilitating one and a half ventricle repair. Use of an extraanatomical shunt may functionally relieve central pulmonary artery obstruction in candidates for Fontan-like circulation.     

Pulmonary Interstitial Glycogenosis: An Unrecognized Etiology of Persistent Pulmonary Hypertension of the Newborn in Congenital Heart Disease?

Background

Pulmonary interstitial glycogenosis (PIG) arises from a developmental disorder of the pulmonary mesenchyme and presents clinically with reversible neonatal respiratory distress and/or persistent pulmonary hypertension of the newborn (PPHN).

Objective

We report two cases of PIG in patients with congenital heart disease (CHD) and evidence of PPHN.

Results

Both cases demonstrated the hallmark PIG histologic finding of diffuse, uniform interstitial thickening due to the presence of immature interstitial cells containing abundant cytoplasmic glycogen.

Conclusions

We report the second and third patients with PIG associated with CHD. Because histologic examination is required to establish the diagnosis, we speculate that PIG, although rare, may be underrecognized in neonates presenting with PPHN in the setting of CHD.     

Intact Right Ventricle–Pulmonary Artery Shunt After Stage 2 Palliation in Hypoplastic Left Heart Syndrome Improves Pulmonary Artery Growth

For patients with hypoplastic left heart syndrome who have undergone the Norwood procedure with a right ventricle–pulmonary artery (RV-PA) shunt, the shunt can either be removed or left intact at the time of the stage 2 procedure. This study aimed to determine the effects of an intact shunt on pulmonary artery growth and clinical outcomes after the stage 2 procedure. A retrospective review of patients who underwent Norwood with an RV-PA shunt from 2005 to 2010 was performed. Catheterization data, echocardiographic data, postoperative outcome variables, and mortality data were collected. Pulmonary artery size was measured at pre-stage 2 and pre-Fontan catheterizations using the Nakata Index and the McGoon Ratio. Of the 68 patients included in the study, 48 had the shunt removed at the time of stage 2 (group 1), and 20 had the shunt left intact (group 2). The two groups did not differ in terms of pre-stage 2 hemodynamics or pulmonary artery size. After stage 2, group 2 had higher oxygen saturations. The two groups did not differ regarding duration of chest tube drainage, length of hospital stay, need for unplanned interventions, or mortality. Before Fontan, the group 2 patients had higher superior vena cava (SVC) pressures and more venovenous collaterals closed. There was increased pulmonary artery growth between the pre-stage 2 and pre-Fontan catheterizations in group 2 using both the Nakata Index (+148.5 vs ?52.4 mm²/m²; p = 0.01) and the McGoon Ratio (+0.36 vs +0.01; p = 0.01). These findings indicate that patients with an intact RV-PA shunt after stage 2 have greater pulmonary artery growth than patients with the shunt removed, with no increased risk of complications.     

Pulmonary function tests in Indian girls — Prediction equations

Objective: The present study was conducted to evaluate pulmonary functions and develop prediction equations in Indian girls.Methods: 1038 normal healthy schoolgirls in the age group of 5 to 15 years were selected for the present study. The anthropometrical parameters like height, weight, sitting height and chest circumference were measured and body surface area (BSA) and fat free mass (FFM) were derived using equations. The pulmonary functions such as FEV₁, FVC, FEV₁/FVC% and PEFR were studied.Results: The height, sitting height, weight, BSA, chest circumference, body fat as well as FEV₁, FVC, FEV₁/FVC% and PEFR were comparable with Indian standards. Multiple regression equations were developed to predict FEV₁, FVC and PEFR using anthropometrical indices like height, fat free mass and age or chest circumference in view of significantly high correlation of these parameters with lung function variables [height and FEV₁ (r-0.90), height and FVC (r-0.899), height and PEFR (r-0.891), chest and FEV₁ (r-0.868), chest and FVC (r-0.867), chest and PEFR (r-0.83)].Conclusion: The regression equations to predict the pulmonary functions were presented using the independent variables like height, fat free mass and chest circumference or age, since these variables have shown very strong predictability for FEV₁, FVC and PEFR. The equations presented in this study can be considered as referral standards for Indian girls.     

Takayasu��s Arteritis Mimicking Unilateral Pulmonary Artery Agenesis in a Child With Severe Pulmonary Hypertension and Right Heart Failure: A Diagnostic Dilemma

Affliction of the pulmonary arteries in Takayasu’s arteritis is uncommon. Moreover the incidence of pulmonary artery involvement in this condition is often underestimated because of asymptomatic nature in most patients. Severe involvement may however present with pulmonary artery hypertension and hemoptysis, which may prove to be fatal. This case report describes a 9-year-old girl with severe pulmonary hypertension and right heart failure secondary to total occlusion of the right pulmonary artery. Detailed clinical examination and computed tomography (CT) angiography confirmed this diagnosis.     

Systemic Arterial Endothelial Function in Children and Young Adults with Idiopathic Pulmonary Arterial Hypertension: Is there a Relation to Pulmonary Endothelium-Dependent Relaxation?

Pulmonary arterial endothelial function is known to be affected in patients with idiopathic pulmonary arterial hypertension (IPAH). Current reports also detected peripheral systemic arterial dysfunction in IPAH patients. The purpose of this study was to assess whether there is a relation between pulmonary arterial and systemic arterial endothelial function. Pulmonary arterial endothelium-dependent relaxation was assessed by changes in pulmonary blood flow in response to acetylcholine which were determined using intravascular Doppler flow measurements. Pulmonary flow reserve (PFR) was calculated as the ratio of pulmonary blood flow velocity in response to acetylcholine relative to baseline values. Systemic arterial endothelial function was assessed by the vascular response to reactive hyperemia, and was recorded non-invasively by peripheral arterial finger tonometry under standardized conditions. Thirteen children and young adults [mean age 16.7 (±5.6) years] with IPAH and 13 age-/gender-matched controls were included in the study. Digital reactive hyperemic index (RHI) of the IPAH patients was 1.54 (±0.69), and of the controls was 1.67 (±0.66) [p = 0.64]. The mean baseline flow velocity in the segmental pulmonary artery of all patients was 18.5 (±5.5) cm/s, increasing to 27.4 (±12.3) cm/s (p = 0.003) during acetylcholine infusion. The calculated mean PFR was 1.48 (±0.4). There was no significant correlation between the PFR and RHI (r = 0.19; p = 0.54). According to our results, systemic arterial endothelial function assessed by peripheral arterial finger tonometry was not significantly impaired in children and young adults with IPAH compared with age-/gender-matched controls. There was no correlation between systemic arterial and pulmonary arterial endothelial function, suggesting that different mechanisms may contribute to their pathogenesis and progression.     

Pulmonary hypertension and oxidative stress: Where is the link?

Oxidative stress can be associated with hyperoxia and hypoxia and is characterized by an increase in reactive oxygen (ROS) and nitrogen (RNS) species generated by an underlying disease process or by supplemental oxygen that exceeds the neutralization capacity of the organ system. ROS and RNS acting as free radicals can inactive several enzymes and vasodilators in the nitric oxide pathway promoting pulmonary vasoconstriction resulting in persistent pulmonary hypertension of the newborn (PPHN). Studies in animal models of PPHN have shown high ROS/RNS that is further increased by hyperoxic ventilation. In addition, antioxidant therapy increased PaO₂ in these models, but clinical trials are lacking. We recommend targeting preductal SpO₂ between 90 and 97%, PaO₂ between 55 and 80 mmHg and avoiding FiO₂ > 0.6–0.8 if possible during PPHN management. This review highlights the role of oxidative and nitrosative stress markers on PPHN and potential therapeutic interventions that may alleviate the consequences of increased oxidant stress during ventilation with supplemental oxygen.     

Pulmonary Artery Banding Before the Damus–Kaye–Stansel Procedure

Subaortic stenosis (SAS) in a single ventricle leads to myocardial hypertrophy and compromises Fontan results. Moreover, controversy exists concerning the optimal surgical strategy for relieving SAS. We have applied pulmonary artery banding (PAB) before the Damus–Kaye–Stansel procedure (DKS), and here we analyze factors that influence systemic ventricular compliance. Thirteen patients underwent PAB before DKS. Median PAB duration was 5.5 months (range, 20 days to 17.7 months). Procedures administered concomitantly with DKS were Blalock–Taussig shunt (n = 6), bidirectional cavopulmonary shunt (n = 5), and Fontan operation (n = 2). All survived and were doing well after a median follow-up 2.7 years. Cardiac catheterization before DKS showed that the mean pressure gradient across the systemic ventricular outflow tract and PAB were 20.6 ± 10.1 and 67.4 ± 10.2 mmHg, respectively. After DKS, systemic ventricular end diastolic pressure (SVEDP) was significantly correlated with PAB duration (r = 0.65, p = 0.022), but not with PAB or systemic ventricle outflow tract pressure gradients. After DKS, SVEDP decreased or fell to within the range in patients with PAB duration less than 7 months (p < 0.05). Seven patients had a successful Fontan operation, and 6 without risk factors are waiting operation. SVEDP was found to be correlated with PAB duration, and our findings indicate that short-term PAB can be considered a safe option in patients with a single ventricle and SAS.     

Branch Pulmonary Artery Growth After Blalock–Taussig Shunts in Tetralogy of Fallot and Pulmonary Atresia with Ventricular Septal Defect: A Retrospective, Echocardiographic Study

We performed a retrospective echocardiographic study in tetralogy of Fallot (TOF) or pulmonay atresia with ventricular septal defect (PA&VSD) to evaluate the effects of Blalock–Taussig shunt on branch pulmonary artery growth. There were 35 patients with TOF and 11 with PA&VSD. We measured the right and left pulmonary artery area index and also the combined pulmonary artery area index, both before and after shunt operation. The mean ± SD of these three variables before the shunt operation in the TOF group were 63.5 ± 22.5, 57.8 ± 24.9, and 121.4 ± 42.8 mm²/m²; after shunt operation they were 98.5 ± 33.6, 85.9 ± 31.9, and 184.0 ± 59.8 mm²/m², respectively (p values <0.0001, <0.0002, and <0.0001, respectively). In the PA&VSD group the comparable values before shunt operation were 66.5 ± 16.0, 55.4 ± 10.6, and 120.9 ± 26.9 mm²/m² and after shunt operation were 90.5 ± 22.9, 77.2 ± 24.1, and 166.6 ± 44.4 mm²/m², respectively (p values <0.0006, <0.014, and <0.002, respectively). We also examined the effect of distensibility of pulmonary arteries by comparing the percentage change in size of the combined pulmonary artery area index in the first 4 months after shunt with those after this time (p < 0.023). There were no significant differences between left- and right-sided shunts, origin and distal pulmonary artery growth, and the TOF and PA&VSD groups.     

Annular and Leaflet Augmentation in Noonan’s Syndrome with Dysplastic Pulmonary Valve

Two patients with dysplastic pulmonary valves associated with Noonans syndrome successfully underwent leaflet augmentation with pericardial membrane and annular enlargement with preservation of valve competence. Both patients are doing well at 36 and 37 months, respectively, postoperatively. Echocardiography and clinical assessment showed gradients of 12 and 16 mmHg, respectively, and negligible pulmonary valve insufficiency. The surgical technique is simple and provides an attractive alternative in patients with dysplastic pulmonary valve and small pulmonary orifice and annulus.     

Platelets in Pulmonary Hypertension: a Causative Role or a Simple Association?

Pathophysiology of pulmonary arterial hypertension is based on three basic mechanisms: thrombotic pulmonary vascular lesions, vasoconstriction and vascular remodeling. Platelets are related to all of these mechanisms by their aggregation, production, storage and release of several mediators. The role of platelets is more prominent in some types of pulmonary arterial hypertension, including those which are secondary to inflammatory and infectious diseases, hemoglobinopathies, essential thrombocythemia, drugs, thromboembolism, and cardiac surgery. Most pulmonary antihypertensive drugs have a negative effect on platelets. In this review, the mechanisms of platelets association with pulmonary arterial hypertension, those types of pulmonary arterial hypertension with greatest platelet contribution to their pathophysiology, and the effects of pulmonary antihypertensive drugs on platelets are summarized.     

Pulmonary function test in transfusion-dependent β-thalassemia major patients: a pilot study

Lung involvement is one of known complications of thalassemia. The aim of this study was to determine predominant type of pulmonary dysfunction and its relationship to iron overload in β-thalassemia children. Fifty thalassemia major children with treatment of regular blood transfusion and desferrioxamine participated in the study. Thirty-three boys and 17 girls (median age 12.5 years) with β-thalassemia enrolled in the study. Other information including body mass index, hematocrit, and the number of years of blood transfusion were recorded. Serum ferritin level and hematocrit were 3346 ± 1667 mg/dL and 27.7 ± 2, respectively. Pulmonary function tests were performed in all subjects for detecting pulmonary dysfunction. Thirty-five patients (70%) with thalassemia had abnormal result of spirometry. Obstructive airway disease based on reduced forced expiratory volume in 1 second (FEV(1)) and FEV(1)/forced vital capacity (FVC) ratio <80% was detected in 4 patients (8%). Six patients (12%) showed restrictive pattern, as defined by a reduction FVC <80% and FEV(1)/FVC ratio ≥80%. In this study, small airway involvement based on presence of forced expiratory flow (FEF(25%-75%)) <60%, FEV(1)/FVC ratio >70%, and FVC >80% was detected in 25 subjects (50%). Decreased values of peak expiratory flow rate (PEF) were detected in 23 (46%) and low FEV(1) in 10 (20%) subjects. There was no significant correlation between abnormal pulmonary function test and serum ferritin level in children with thalassemia. This study showed small airway disease was predominant abnormality in thalassemia patients, although additional larger studies are needed to evaluate underlying mechanisms and validate these findings.     

Pulmonary infections and community associated methicillin resistant Staphylococcus aureus: a dangerous mix?

The incidence of complicated pneumonias in children is increasing with a concurrent increase in the incidence of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections. CA-MRSA is distinct from hospital associated MRSA [HA-MRSA] in regards to its genotype, epidemiology, and clinical course. Unlike HA-MRSA, CA-MRSA often strikes young, previously healthy children. Pneumonias caused by CA-MRSA have a rather distinct presentation. Because of its pore-forming toxins, namely Panton-Valentine leukocidin (PVL) and alpha-hemolysin, extensive necrotizing disease with corresponding hypoxaemia and hypercarbia is common. Other features include multilobar disease, leucopenia, haemoptysis, and high mortality rates. A previous influenza-like illness or skin and soft tissue infection [SSTI] often precede the development of pneumonia due to CA-MRSA. Vancomycin is recommended as first-line empiric therapy for suspected CA-MRSA infections. However, vancomycin is not an ideal agent for the treatment of pneumonia given its poor concentrating ability in alveolar fluid. Linezolid and clindamycin have also been used in the treatment of CA-MRSA pneumonia and ongoing research is looking for alternative antimicrobials. Recent studies have continued to report a lack of correlation between nasal colonization and active infections due to CA-MRSA. Given that the role of nasal colonization in CA-MRSA infection is not clear, the utility of decolonization treatment has been a point of debate. Finally, patients with cystic fibrosis are becoming increasingly colonized with MRSA as opposed to MSSA. There is some accumulating evidence that patients with MRSA show a more rapid deterioration in their degree of obstructive disease as measured by forced expiratory volume in one second (FEV₁). However, it still is not clear whether MRSA is a marker for worsening disease or whether it actually is a cause of disease progression in cystic fibrosis. More longitudinal data is needed to understand how MRSA colonization impacts the course of disease in cystic fibrosis.     

Pulmonary inflammatory myofibroblastic tumor after Hodgkin’s lymphoma and application of PET imaging

Inflammatory myofibroblastic tumor (IMT) is a rare tumor with a particular histological pattern of myofibroblasts and mixed inflammatory infiltrate. IMT has been rarely described in association with malignancy. This case report is of a 16-year-old male who had Hodgkin's disease (stage IVA) and who after chemotherapy and radiotherapy developed IMT, 16 months post completion of therapy. The IMT was in the lung in an area which was previously involved with HD and had undergone radiotherapy. PET imaging with F(18)FDG was used in the initial diagnosis and has been used in follow-up after full surgical resection of the lesion.