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(Circulation. 2004;110:II-139 – II-146.)
© 2004 American Heart Association, Inc.

Surgery for Congenital Heart Disease

Hypoplasia of the Small Pulmonary Arteries in Hypoplastic Left Heart Syndrome With Restrictive Atrial Septal Defect

Katsuhide Maeda, MD; Shigeo Yamaki, MD; Hideaki Kado, MD; Toshihide Asou, MD; Arata Murakami, MD; Shinichi Takamoto, MD

From the Department of Cardiothoracic Surgery (K.M., A.M., S.T.), Graduate School of Medicine, University of Tokyo, Japan; Japanese Research Institute of Pulmonary Vasculature (S.Y.), Miyagi, Japan; Fukuoka City Children’s Hospital (H.K.), Fukuoka, Japan; and Faculty of Medicine (T.A.), Kitazato University, Kanagawa, Japan.

Correspondence to Katsuhide Maeda, MD, Department of Cardiothoracic Surgery, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan. E-mail maedak-tky{at}umin.ac.jp

Background— Restrictive atrial septal defect (ASD) (including intact atrial septum [IAS]) has been reported to be a risk factor that negatively impacts survival in hypoplastic left heart syndrome (HLHS). Although lymphangiectasia and "arterialization" of the veins of the lung in HLHS with restrictive ASD have been reported, they cannot fully explain the high mortality. We have introduced a new method of evaluating the development of the pulmonary vasculature in histological sections and used it to assess patients’ lungs. We tested the hypothesis that the small pulmonary arteries (SPA), which are pulmonary arteries in a histological section whose radii are 25 µm to 250 µm, in HLHS with restrictive ASD are hypoplastic, but that the alveoli are not, to elucidate the mechanism underlying the poor outcome of these patients.

Methods and Results— Fourteen HLHS patients between 1 day and 40 days of age were studied. In 8 cases, the ASD was restrictive [R(+) group], and in the other 6 cases it was not [R(–) group]. Specimens from 12 autopsies of cases with no congenital heart or pulmonary disease were examined as a control group (C group). As a novel histological parameter, we assessed the size of SPA in relation to the size of accompanying bronchioles to identify SPA underdevelopment. To evaluate the development of alveoli and interstitial tissue, radial alveolar counts (RAC), which reflect alveolar maturity and complexity, were also performed. Statistical comparisons between groups were made by analysis of covariance with age as a covariant factor. When the radius of the accompanying bronchiole was 100 µm, the radius of the SPA was 34.0±10.8 µm in the R(+) group, and significantly lower than the 46.6±8.5 µm in R(–) group (P=0.0022) and 70.5±8.4 µm in the C group (P<0.0001). The RAC was in 3.5±0.9 in the R(+) group, 3.4±0.6 in the R(–) group, and 3.7±0.9 in the C group (no significant differences between groups).

Conclusion— The SPA in HLHS with restrictive ASD were underdeveloped compared with the SPA in HLHS with nonrestrictive ASD and the controls, but their alveoli were not hypoplastic. Based on these results, it is speculated that SPA hypoplasia may be responsible for the poor outcome of HLHS with restrictive ASD.

Key Words: hypoplastic left heart syndrome • restrictive atrial septal defect • lung pathology • hypoplastic pulmonary artery