Successful Treatment of Pulmonary Artery Aneurysm With Atrioventricular Septal Defect and Pulmonary Hypertension: Clinical and Pathologic Features

We describe an adult female case of pulmonary artery aneurysm (PAA) associated with atrioventricular septal defect and pulmonary hypertension (PH) who underwent successful treatment. To the best of our knowledge, this is the first case that provides detailed and novel pathologic findings using multiple staining methods, indicating an imminent state of vessel rupture. The histology reconfirms the high risk of dissection in PAA cases associated with long-term untreated congenital heart disease and PH. A 58-year-old woman presented with palpitations and fatigue. She was diagnosed with a partial atrioventricular septal defect in infancy but stopped visiting the hospital on her own decision during adolescence. She has no family history of cardiovascular disease. Chest radiography revealed cardiomegaly and marked enlargement of the pulmonary artery (Fig. 1A). Echocardiography showed a dilated right atrium and right ventricle, atrial septal defect of both ostium primum and ostium secundum types, and no interventricular shunt (Fig. 1B). The parasternal long-axis view revealed a massively enlarged main pulmonary artery with a diameter of 73 mm (Fig. 1C). Computed tomography showed a markedly dilated main pulmonary artery and proximal right and left pulmonary artery with diameters of 60 mm, 45 mm, and 38 mm, respectively (Fig. 1D-F; Video 1 , view video online). At cardiac catheterization, the pulmonary-systemic flow ratio was 3.5, the mean pulmonary artery pressure 29 mm Hg, and the pulmonary vascular resistance 2.8 wood units. Her clinical characteristics and laboratory examinations did not suggest any type of connective tissue disease and autoimmune diseases as well as genetic syndromes associated with aortic aneurysms, although no testing for chromosomal and/or genetic alterations including somatic mosaicism has been done. A contrast computed tomography scan showed no aortic root dilation with a size of 29.3 mm and no other obvious abnormalities in systemic arteries other than the pulmonary artery. She underwent successful PAA plication and intracardiac repair. During surgery, a markedly enlarged pulmonary artery trunk was observed (Supplemental Fig. S1), with no flap in the intima (Supplemental Fig. S2). Pathologic examination of PAA tissue revealed patchy-extensive smooth muscle cell loss in the tunica media by haematoxylin and eosin staining (Fig. 2A), severe extensive fragmentation of elastic fibres and thin-multifocal laminar medial collapse by Elastica van Gieson staining (Fig. 2B), and severe-extensive translamellar mucoid extracellular matrix deposition by Alcian blue staining (Fig. 2C), indicating severe medial degeneration of the pulmonary artery wall. Postoperative cardiac catheterization showed residual PH, which improved after surgery, with a mean pulmonary artery pressure of 21 mm Hg and a pulmonary vascular resistance of 2.7 wood units. Three years after the operation, no recurrence of PAA was found, and the patient was doing well on an oral pulmonary vasodilator.Figure 2(A) Haematoxylin and eosin staining shows smooth muscle cell loss in the tunica media (white arrows). (B) Elastica van Gieson staining shows fragmentation of the elastic fibre (white arrows) and laminar medial collapse (black arrows). (C) Alcian blue staining shows translamellar mucoid extracellular matrix deposition (white arrows). Scale bars = 250 mm.View Large Image Figure ViewerDownload Hi-res image Download (PPT) PAA is a rare disease with an incidence of 1/14,000 in autopsy cases1Duijnhouwer A.L. Navarese E.P. Van Dijk A.P. et al.Aneurysm of the pulmonary artery, a systematic review and critical analysis of current literature.Congenit Heart Dis. 2016; 11: 102-109Crossref PubMed Scopus (43) Google Scholar and is usually defined as a main pulmonary artery diameter >40 mm. Surgical repair is recommended for the maximum PAA diameter >55 mm to prevent life-threatening rupture,2Kreibich M. Siepe M. Kroll J. et al.Aneurysms of the pulmonary artery.Circulation. 2015; 131: 310-316Crossref PubMed Scopus (122) Google Scholar and the following conditions have also been reported as the risk of dissection: identification of the causative mechanism, systolic pulmonary artery pressure >50 mm Hg especially associated with congenital heart disease, or pulmonary artery diameter >75 mm. Regarding changes in pulmonary artery diameter over time, an annual increase of 2 mm is reported to be an important risk factor for vessel rupture.1Duijnhouwer A.L. Navarese E.P. Van Dijk A.P. et al.Aneurysm of the pulmonary artery, a systematic review and critical analysis of current literature.Congenit Heart Dis. 2016; 11: 102-109Crossref PubMed Scopus (43) Google Scholar Our patient had congenital heart disease, an important risk factor for PAA development and dissection.1Duijnhouwer A.L. Navarese E.P. Van Dijk A.P. et al.Aneurysm of the pulmonary artery, a systematic review and critical analysis of current literature.Congenit Heart Dis. 2016; 11: 102-109Crossref PubMed Scopus (43) Google Scholar,2Kreibich M. Siepe M. Kroll J. et al.Aneurysms of the pulmonary artery.Circulation. 2015; 131: 310-316Crossref PubMed Scopus (122) Google Scholar Congenital heart disease causes high shear stress on the pulmonary artery wall because of left-to-right shunt-associated increased pulmonary blood flow and/or pulmonary valvular disease–associated turbulent flow, resulting in dilatation of the pulmonary artery.2Kreibich M. Siepe M. Kroll J. et al.Aneurysms of the pulmonary artery.Circulation. 2015; 131: 310-316Crossref PubMed Scopus (122) Google Scholar The large interatrial left-to-right shunt caused by the partial atrioventricular septal defect and ostium secundum–type atrial septal defect would have exposed the pulmonary artery wall to a significant mechanical stretch and a high shear stress over the years, affecting the development of PAA. To the best of our knowledge, this is the first histologic examination of PAA with a detailed and comprehensive approach using multiple staining methods, providing novel pathologic findings. The previous literature reported cystic medial necrosis in PAA tissue;2Kreibich M. Siepe M. Kroll J. et al.Aneurysms of the pulmonary artery.Circulation. 2015; 131: 310-316Crossref PubMed Scopus (122) Google Scholar however, overall assessments were inadequate because only a partial staining method was used. Recently, comprehensive and graded histologic classification has been recommended in patients with aortic dissection to investigate the correlation between pathologic changes and their etiology or clinical prognosis.3Halushka M.K. Angelini A. Bartoloni G. et al.Consensus statement on surgical pathology of the aorta from the Society for Cardiovascular Pathology and the Association For European Cardiovascular Pathology: II. Noninflammatory degenerative diseases—nomenclature and diagnostic criteria.Cardiovasc Pathol. 2016; 25: 247-257Crossref PubMed Scopus (156) Google Scholar,4Waters K.M. Rooper L.M. Guajardo A. Halushka M.K. Histopathologic differences partially distinguish syndromic aortic diseases.Cardiovasc Pathol. 2017; 30: 6-11Crossref PubMed Scopus (19) Google Scholar In patients with aortic dissection, severe medial degenerative changes, aortic aneurysm formation, and vessel rupture are caused by several mechanisms, including abnormal haemodynamic force due to hypertension or congenital heart disease, and aging processes of the aortic media, combined with connective tissue disorders in some cases.3Halushka M.K. Angelini A. Bartoloni G. et al.Consensus statement on surgical pathology of the aorta from the Society for Cardiovascular Pathology and the Association For European Cardiovascular Pathology: II. Noninflammatory degenerative diseases—nomenclature and diagnostic criteria.Cardiovasc Pathol. 2016; 25: 247-257Crossref PubMed Scopus (156) Google Scholar,4Waters K.M. Rooper L.M. Guajardo A. Halushka M.K. Histopathologic differences partially distinguish syndromic aortic diseases.Cardiovasc Pathol. 2017; 30: 6-11Crossref PubMed Scopus (19) Google Scholar A recent report suggested that such degeneration may correlate with the severity of aortic enlargement due to various vascular stresses in noninflammatory vessels.5Amemiya K. Ishibashi-Ueda H. Mousseaux E. et al.Comparison of the damage to aorta wall in aortitis versus noninflammatory degenerative aortic diseases.Cardiovasc Pathol. 2021; 52107329Crossref PubMed Scopus (1) Google Scholar Our case showed severe medial degeneration of the pulmonary artery wall. Although the wall of the pulmonary artery is thinner than the wall of the aorta, the same changes that occur in aortic dissection are seen in the vessel wall of pulmonary aneurysms in our case, suggesting that there may be a common pathologic mechanism causing degeneration of the wall structure in the pulmonary artery as in the aorta. The main cause of damage on the pulmonary artery wall is thought to be abnormal haemodynamic stress due to congenital heart disease and PH in addition to the aging process of the vascular wall.2Kreibich M. Siepe M. Kroll J. et al.Aneurysms of the pulmonary artery.Circulation. 2015; 131: 310-316Crossref PubMed Scopus (122) Google Scholar,3Halushka M.K. Angelini A. Bartoloni G. et al.Consensus statement on surgical pathology of the aorta from the Society for Cardiovascular Pathology and the Association For European Cardiovascular Pathology: II. Noninflammatory degenerative diseases—nomenclature and diagnostic criteria.Cardiovasc Pathol. 2016; 25: 247-257Crossref PubMed Scopus (156) Google Scholar Severe medial degeneration leads to a progressive weakening of the wall structure and eventually to a giant aneurysm. The accumulated assessment of the severity of medial degenerative changes in pulmonary arteries obtained by a comprehensive histologic approach can provide important insights into the clinical-histologic correlations that accurately predict the extent of pulmonary vascular injury and the risk of vessel rupture, especially in cases of PAA with multiple risk factors such as long-term untreated congenital heart disease and PH. In conclusion, health care professionals should be aware of PAA development and rupture in adult patients with long-term untreated congenital heart disease and PH. When the PAA is diagnosed, the aneurysm’s etiology, size, and growth rate should be evaluated carefully. In the case of risk factors such as a very large or progressive aneurysm, surgery for the underlying disease and aneurysm should be immediate to avoid catastrophic rupture.Novel Teaching Points•We propose that comprehensive pathologic findings using multiple staining methods may predict the extent of pulmonary vascular injury and the risk of vessel rupture from a detailed evaluation of an adult PAA patient with long-term untreated congenital heart disease and PH.•Health care professionals should be aware of PAA development and rupture in adult patients with long-term untreated congenital heart disease and PH. •We propose that comprehensive pathologic findings using multiple staining methods may predict the extent of pulmonary vascular injury and the risk of vessel rupture from a detailed evaluation of an adult PAA patient with long-term untreated congenital heart disease and PH.•Health care professionals should be aware of PAA development and rupture in adult patients with long-term untreated congenital heart disease and PH. The authors assert that all procedures contributing to this work complied with the ethical standards of the relevant national guidelines on human experimentation (Japan) and with the Helsinki Declaration of 1975 (as revised in 2013).