Prospective diagnosis of alveolar capillary dysplasia in infants with congenital heart disease

A lveolar capillary dysplasia (ACD) is a uniformly lethal lung disorder found in newborns that is characterized by severe pulmonary hypertension and hypoxemia. Histologically, it is identified by inadequately capillarized alveoli.1 The association of ACD with abnormalities in other organ systems, notably the genitourinary and gastrointestinal tracts, has been established and is seen in approximately 60% of cases.2–4 The association of ACD with structural heart disease, however, has only just recently been reported.5 From 1991 to 1998, we identified 4 patients with histologically proven ACD who underwent treatment at our institution. Two of the 4 patients had associated structural heart disease, which consisted of an atrioventricular septal defect (AVSD), mild left ventricular hypoplasia, and coarctation of the aorta. In addition to the 4 patients described in the following, 2 additional patients with histories suggestive of ACD, including 1 with an AVSD and aortic arch hypoplasia, were noted, but not included in this report because requests for autopsy or lung biopsy were declined, and a definitive diagnosis was unavailable. Although many initial clinical findings and problems might have been attributed to their anatomic heart disease, the superimposition of ACD resulted in an atypical and labile clinical course, which became explainable once the diagnosis of ACD had been established. Importantly, based on previous experience and clinical suspicions, we were able to prospectively diagnose ACD in 1 of our most recent patients, thereby avoiding futile and prolonged clinical interventions. Such a prospective diagnosis of ACD in a patient with congenital heart disease has, to our knowledge, not previously been reported. In this report, we review our institutional experience with this disorder, emphasizing the clinical characteristics that might suggest the presence of ACD in infants with associated cardiac disease. • • • Patient 1 was born at 36 weeks’ gestation. At 3 hours of life, she developed progressive respiratory distress necessitating intubation. Chest x-ray showed bilateral infiltrates. An echocardiogram revealed right ventricular hypertrophy, right atrial enlargement, a patent ductus arteriosus (PDA) and a patent foramen ovale, both with bidirectional shunting. The child was placed on extracorporeal membrane oxygenation (ECMO) at 48 hours of life due to persistent refractory hypoxemia. Right heart catheterization on ECMO in the neonatal intensive care unit showed suprasystemic pulmonary artery pressures with high pulmonary vascular resistance. Tolazoline was ineffective. On day 20, hemofiltration was initiated due to progressive renal failure. Subsequently, the infant deteriorated further. Echocardiogram showed a nondilated and poorly contractile left ventricle with no anterograde flow. The decision was made to withdraw support, and the baby expired. Postmortem examination revealed ACD. In addition, there were associated congenital abnormalities, including short small bowel and hypoplasia of the gall bladder and appendix. The heart was structurally normal with unobstructed pulmonary veins. Patient 2 was delivered at 41 weeks’ gestation. He required mechanical ventilation and was transferred to this center for consideration of ECMO. Echocardiogram showed a structurally normal heart with normal biventricular function, a PDA with right-to-left shunting consistent with suprasystemic pulmonary artery pressures, and a patent foramen ovale with bidirectional shunting. ECMO was initiated, and after a 5-day ECMO course, he was weaned off support and extubated. He subsequently required reintubation. Due to his poor clinical course of unclear etiology, a lung biopsy was performed before his death and revealed ACD. Patient 3 was born at 36 weeks’ gestation. He developed respiratory distress, required intubation and remained hypoxic despite 100% oxygen. The initial chest xray was consistent with respiratory distress syndrome. He was started on tolazoline for presumed persistent pulmonary hypertension and was transferred to this institution for consideration of ECMO. Echocardiography demonstrated a primum atrial septal defect, cleft mitral valve, mild left ventricular hypoplasia, transverse aortic arch hypoplasia, and coarctation (Table I, patient 3). He was started on a prostaglandin E1 infusion, and was weaned off oxygen. He had multiple transient arterial desaturations due to right-to-left ductal shunting. He had a brief trial of nitric oxide, which did not improve his oxygenation. He subsequently underwent surgery to repair his coarctation and aortic arch hypoplasia. Postoperatively, he had suprasystemic pulmonary artery pressures, metabolic acidosis, episodic desaturation, bradycardia, and hypotension. He developed progressive multiorgan failure, became anuric, and expired despite aggressive therapy. Postmortem examination revealed ACD as well as pulmonary interstitial emphysema, pleural effuFrom the Departments of Pediatrics and Surgery, Case Western Reserve University School of Medicine, Cleveland, Ohio. Dr. Lane’s address: Division of Pediatric Cardiology, University Hospitals of Cleveland, Cleveland,Ohio44106.E-mail:jrl2@po.cwru .edu. Manuscript received November 3, 1998; revised manuscript received and accepted April 16, 1999.