Chida-Nagai A, Sagawa K, Tsujioka T, Fujimoto T, Taniguchi K, Sasaki O, Izumi G, Yamazawa H, Masaki N, Manabe A, Takeda A.
Heart Vessels. 2020 Apr 13. doi: 10.1007/s00380-020-01604-1. [Epub ahead of print] PMID: 32285188 Free PMC Article
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Congenital heart disease-associated pulmonary arterial hypertension (CHD-PAH) is one of the major complications in patients with CHD. A timely closure of the left-to-right shunt will generally result in the normalization of the pulmonary hemodynamics, but a few patients have severe prognosis in their early childhood. We hypothesized that wide-ranging pathological mechanism in PAH could elucidate the clinical state of severe CHD-PAH. Using electronic medical records, we retrospectively analyzed six infants with severe CHD-PAH who had treatment-resistant PH. All patients were born with congenital malformation syndrome. After starting on a pulmonary vasodilator, five of the six patients developed complications including pulmonary edema and interstitial lung disease (ILD), and four patients had alveolar hemorrhage. After steroid therapy, the clinical condition improved in four patients, but two patients died. The autopsy findings in one of the deceased patients indicated the presence of recurrent alveolar hemorrhage, pulmonary venous hypertension, ILD, and PAH. Based on the clinical course of these CHD-PAH in patients and the literature, CHD-PAH can occur with pulmonary vascular obstructive disease (PVOD)/pulmonary capillary hemangiomatosis (PCH), ILD, and/or alveolar hemorrhage. The severity of CHD-PAH may depend on a genetic disorder, respiratory infection, and upper airway stenosis. Additionally, pulmonary vasodilators may be involved in the development of PVOD/PCH and ILD. When patients with CHD-PAH show unexpected deterioration, clinicians should consider complications associated with PVOD/PCH and/or pulmonary disease. In addition, the choice of upfront combination therapy for pediatric patients with CHD-PAH should be selected carefully.
Fig. 1 Chest HRCT scan of patient 2. At 145 days of age, patient 2’s lung HRCT image shows panlobular ground-glass opacity and interlobular septal thickening. HRCT high-resolution computed tomography
Fig. 2 Histopathological findings of the lung autopsy for patient 2 at 181 days of age. a Small pulmonary arteries with a diameter of 50 µm have a medial thickness. Yellowish hemosiderin deposition is also found. b Almost 50% of the pulmonary veins have intimal fibrous thickening. c There are many emphysematous bullae and hemosiderin deposits. d Fibrous thickening of the wall of a pulmonary alveolus is revealed. The central white area is lymphangiectasia
Fig. 3 Chest HRCT scan of patient 3 illustrating fibrosis and alveolar hemorrhage. a At 188 days of age, patient 3’s lung HRCT image shows honeycomb cysts involving the subpleural area, alveolar hemorrhage, and parenchymal opacification consisting of consolidation and ground-glass opacities. b At 197 days of age, the HRCT scan revealed dilated pulmonary arteries totally. c At 210 days of age, the follow-up HRCT scan after steroid treatment, cessation of pulmonary vasodilators, and pulmonary artery banding shows marked improvement of the previous findings. HRCT high-resolution computed tomography
Fig. 4 Chest HRCT image of the others. a The HRCT image of patient 1 reveals interlobular septal thickening and interlobar pleura thickening. b The HRCT image of patient 4 shows panlobular ground-glass opacity, mild interlobular septal thickening, and funicular shadows. c In patient 5 image, only atelectasis and funicular shadows are shown. d Patient 6 image demonstrates ground-glass opacity, interlobular septal thickening, air space consolidation, and atelectasis. HRCT high-resolution computed tomography
Fig. 5 Estimated mechanism of severe CHD-PAH. CHD-PAH congenital heart disease-associated pulmonary arterial hypertension, PVOD pulmonary veno-occlusive disease, PCH pulmonary capillary hemangiomatosis