Conference: 2018 PHA International PH Conference & Scientific Sessions
Release Date: 06.28.2018
Presentation Type: Abstracts
File Download: Conference 2018_1067
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Abstract presented at the 2018 International PH Conference and Scientific Sessions in Orlando, Fla., June 28-July 1, 2018.
To describe a case study with implications for advanced pulmonary vasodilator therapy in an atypical presentation of alveolar capillary dysplasia with misaligned veins.
Alveolar capillary dysplasia with misalignment of the pulmonary veins (ACDMPV) is a rare developmental lung disorder (Janney et al., 1981). The pathological findings of ACDMPV are described as malposition of pulmonary veins adjacent to small pulmonary arteries, medial thickening of small pulmonary arteries, deficient lobular development, a paucity of alveolar wall capillaries, and occasional lymphangiectasis (Langston, 1991). Infants with ACDMPV are most often full term, and typically present within the first few hours to days life with hypoxemic respiratory failure and severe, refractory persistent pulmonary hypertension of the newborn (PPHN) that is unresponsive to pharmacologic agents and extracorporeal membrane oxygenation (ECMO) (Sen et al., 2004; Chelliah et al., 1995; Steinhorn et al., 1997). Other congenital anomalies involving the cardiac, gastrointestinal genitourinary and musculoskeletal systems are common (Sen et al., 2004; Bishop et al., 2011). Additionally, heterozygous mutations or genomic deletions of the FOXF1 gene have been reported in 80-90% of infants with ACDMPV (Reiter et al. 2016; Szafranski et al., 2016). In the last two decades late and atypical presentations of infants with ACDMPV have been described (Abdallah et al., 1993; Licht et al., 2004; Shankar et al., 2006; Ahmed et al., 2008; Kodama et al. , 2012; Ito et al., 2015, Reiter et al., 2016).
This case study will describe a full term, one-month old female infant with a history of omphalocele, repaired DOL 1, who presented with acute on chronic respiratory distress, hypoxia, and fever. An echo at that time demonstrated suprasystemic right ventricular pressures and a right-to-left atrial shunt. Persistent hypoxia led to intubation and treatment with inhaled nitric oxide (iNO), milrinone, and epinephrine. Initiation of iNO increased systemic saturations from low 80’s to high 90’s. A lung biopsy demonstrating a confirmatory diagnosis of ACDMPV was well tolerated. Interestingly, the pathology was patchy, with areas of normal alveolar-capillary units. Her genetics were positive for a Phe85Leu mutation of the FOXF1 gene. Given her atypical presentation, patchy pathology, and sustained response to iNO, she was aggressively treated with advanced pulmonary vasodilator therapy (sildenafil and subcutaneous treprostinil). The goal of treatment was to enable discharge to home and undergo outpatient evaluation for lung transplant. Her response to advanced therapy has been dramatic. An echocardiogram obtained one month after initiation of therapy has estimated RV is ~50% systemic, saturations remain in the 90’s, and the infant is tolerating enteral feeds with good weight gain.
Infants with ACDMPV presenting outside the neonatal period suggest there are phenotypical variations of the disease. More recent case reports have described infants with ACDMPV and FOXF1 gene mutations (Kodama et al. 2012; Ito et al. 2015; Reiter J et al. 2016) surviving outside the neonatal period. The longest living child with ACDMPV and FOXF1 gene mutation described in the literature was 38-months-old (Ito et al. 2015). Additionally, unlike in classic ACDMPV, histopathologic findings of this infant were not distributed uniformly and were not diffuse. More recently, infants with late and atypical presentations ACDMPV have undergone successful bilateral lung transplantations. Towe et al. (2018) presented a case series from St. Louis Children’s Hospital/Washington University in which 6 infants with atypical ACDMPV underwent bilateral lung transplantations between 4-20 months of age. Three transplanted children are alive at 5-16 years of age, similar to outcomes for infants transplanted for other indications. As demonstrated by this case study, advanced pulmonary vasodilator therapies may prolong time to transplant for infants with atypical presentation of ACDMPV.
Chest CT with angio