Pediatr Cardiol 13:233-236, 1992
Pediatric Cardiology 9 Springer-VerlagNew York Inc. 1992
N e c r o t i z i n g Arteritis in U n c o r r e c t e d T e t r a l o g y o f Fallot with Pulmonary Atresia Jo-Ann Andriko] Max Robinowitz, 3 John Moore, 2 and Renu Virmani 3 Departments of ~Pathology and ZCardiology, Walter Reed Army Medical Center, Washington, D.C. and 3Department of Cardiovascular Pathology, Armed Forces Institute of Pathology, Washington, D.C., USA
SUMMARY. A 10-year-old girl with uncorrected tetralogy of Fallot with pulmonary atresia presented with fevers of unknown origin and left lung infiltrates. At autopsy, necrotizing vascular changes resembling those of severe pulmonary hypertension (grade VI in the HeathEdwards classification) were confined to the left lung. Pulmonary blood flow and pressure were greater in the left lung and were provided by an enlarged collateral artery arising directly from the descending thoracic aorta. To our knowledge, this is the first report of necrotizing arteritis of the pulmonary arteries in uncorrected tetralogy of Fallot with pulmonary atresia. KEY WORDS: Tetralogy of Failot - - Pulmonary hypertension - - Necrotizing arteritis - - Pulmonary atresia with ventricular septal defect
Severe pulmonary hypertension does not occur after corrective surgery for tetralogy of Fallot; however, pulmonary hypertension in patients without corrective surgery may occur. In unoperated patients, pulmonary arterial pressure is modulated by the presence of stenotic segments in the aortopulmonary collateral circulation [1-3, 5, 8]. We present a case of unilateral pulmonary hypertension with fulminant necrotizing arteritis in a patient with uncorrected tetralogy of Fallot with pulmonary atresia (pulmonary atresia with a ventricular septal defect). We propose that the hypertensive changes resulted from increased blood flow through a large aortopulmonary collateral vessel lacking protective stenosis.
Case Report The patient was a 10-year-old white girl with cyanotic congenital heart disease diagnosed at 2 weeks of age. Cardiac catheterization at 2 months and 6 years of age showed a ventricular septal defect, overriding of the aorta (50%), pulmonic atresia and supThe opinions or assertions contained herein are the private views of the authors and are not to be construed as official or reflecting the views of the Department of the Army or the Department of Defense. Address offprint requests to: Dr. Renu Virmani, Department of Cardiovascular Pathology, Armed Forces Institute of Pathology, Washington, D.C. 20306-6000, USA.
ply to the pulmonary circulation by direct collaterals from the descending thoracic aorta, and no evidence of true pulmonary arteries. Selective angiography of her major left lung collateral artery demonstrated a large vessel without stenosis supplying all segments of the left pulmonary vascular bed. Pressure measured in this vessel was equal to aortic pressure (102/67, mean 83 mmHg). Aortography also demonstrated at least two major collaterals, anterior, supplying the right lung. Each of these vessels had significant stenotic segments. Thus, this patient had a left pulmonary vascular bed chronically exposed to high pressure and flows, and a fight pulmonary vascular bed which was protected from these phenomena. It was decided that the patient was inoperable for palliative or corrective surgery, The patient did well with reasonable exercise tolerance until 1 month prior to admission when she developed persistent sore throat and fever unresponsive to oral antibiotics. Blood, urine, and throat cultures were negative. Pulmonary infiltrates in the left lung were present on chest radiographs. On admission, her blood pressure was 126/74 mmHg, her oral temperature 103~ and breath sounds were decreased on the left side. A grade III/VI continuous murmur was heard at the sternum associated with a prominent ventricular heave. The extremities showed clubbing and cyanosis. Laboratory findings were remarkable for a hematocrit of 33%, white blood cell count of 14.7 mm 3, and lactate dehydrogenase of 367 IU/L (normal 0-185 IU/L). Despite institution of broadspectrum antibiotics, she continued to have fever spikes to 103~ and radiographic progression of pneumonia and pleural effusions. A left thoracentesis yielded negative infectious disease cultures. No vegetations were seen on echocardiogram. Ten days after admission the patient complained of poorly localized mid-epigastric pain. Two days later she suddenly collapsed and failed to respond to advanced resuscitative measures.
234
Fig. 1. Sections from the left lung showing muscular pulmonary arteries involved by fibrinoid necrosis of vessel wail with loss of internal elastic lamina. (A) Disruption of the wall with aneurysmal dilatation and intimal fibromuscular proliferation (Movat pentachrome; original magnification, • (B) Early plexiform lesion (Movat pentachrome; original magnification, • (C) Higher power view of vessel wall showing mononuclear and plasma cell inflammation and fibrin deposition (Movat pentachrome; original magnification, x300). (D) Higher power view of vessel wall replaced by granulation tissue (Movat pentachrome; original magnification, x 150).
Pathologic Findings At autopsy, the heart showed a high ventricular septal defect measuring 1.6 cm in diameter, overriding aorta, and right ventricular dilatation and hypertrophy. The pulmonary valve was absent and the main pulmonary artery was a thin cord-like structure measuring 2 mm in external diameter. The right and left pulmonary arteries were markedly hypo-
Pediatric Cardiology Vol. 13, No. 4, 1992
plastic but contained a lumen. The left lung was supplied by a single enlarged aortopulmonary collateral and the right lung by two enlarged aortopulmonary collaterals from the descending thoracic aorta to the hilum of each lung. The diameter of the left collateral measured 1.0 cm and each of the right collaterals measured 0.6 cm. On dissection and serial sectioning, the left collateral was a thin-walled vessel with no segments of stenosis. In contrast, the lumens of both right collaterals were severely stenosed at their origins from the aorta. Gross examination of the lungs showed marked congestion and prominent pulmonary vessels on cut surface. The left lung exhibited multiple nodular areas of fresh parenchymal hemorrhage surrounding pulmonary artery branches which appeared thrombosed. Microscopic examination of the left lung showed multiple hemorrhagic infarcts and markedly dilated arteries containing thrombi in various stages of organization. There was widespread acue inflammation and necrosis of pulmonary arterial walls in association with extensive intraparenchymal hem-
Andriko et al.: Necrotizing Arteritis
Fig. 2. Comparison of muscular pulmonary arteries in the left lung versus the right lung. (A) Well-developed plexiform lesion in left lung (Movat pentachrome; original magnification, x 150). (B) Obliterative fibromuscular intimal proliferation with condensation of elastic fibers in left lung (Movat pentachrome; original magnification, x 150), (C) Thin-walled dilated pulmonary arteries in the subpleural area of the right lung showing an absence of pulmonary hypertensive changes (Movat pentachrome; original magnification, • 150).
orrhage. The small muscular pulmonary arteries and arterioles showed widespread medial hypertrophy and obliterative fibromuscular intimal proliferation with occasional plexiform lesions. Multiple foci of fibrinoid necrosis of the vessel walls (Figs. 1 and 2) were negative for bacteria and fungi. Viral inclusions were not present. The pulmonary arteries and arterioles of the right lung were dilated and thinwalled without vascular changes of pulmonary hypertension or necrotizing arterifis (Fig. 2). Arteritis and intimal proliferation were absent in the other organs.
Discussion
In pulmonary atresia with ventricutar septal defect, patient survival depends on the size and continued patency of the collateral arteries to the lungs. The collateral arteries can be quite large and usually arise directly from the descending thoracic aorta, as in this case, or indirectly from major arterial
235
branches of the aorta (e.g., subclavian or internal mammary arteries) [4, 6, 8]. Intrapulmonary arteries often vary greatly in size and can be quite large distal to the systemic-pulmonary anastomosis [6]. Stenosis of major aortopulmonary collaterals is a well-described feature since the first angiographic report by Jefferson et al. in 1972 [3]. Later reports documented that the stenosis of the collaterals prevents the full transmission of blood flow and pressure from the systemic to pulmonary vasculature [7]. These constricted segments can occur at the origin of collateral from the aorta, along their course, or at anastomoses with pulmonary arteries [1, 2]. Haworth and Macartney [2] in a study of 11 cases of pulmonary atresia with ventricular septal defect found stenosed segments in 58.8% of collaterals with all patients having at least one stenosed vessel. In a radiographic study, 42% of collateral arteries arising from the aorta were stenosed, the most common location being the junction of the collateral with the hilar pulmonary artery [4]. Microscopically, intimal proliferation is the major finding varying in extent from a small area to large intimal cushions which virtually obliterate the vessel lumina [1, 2]. An aortopulmonary anastomosis without a stenosis may result in severe pulmonary vascular changes; Haworth and Macartney [2] and Jefferson et al. [3] describe this as rare occurrences in their series. Necrotizing arteritis is a feature of end-stage pulmonary hypertension associated with large congenital left-to-right shunts and can occur in tetralogy of Fallot following systemic to pulmonary
236
anastomosis operations [9]. Necrotizing arteritis in the setting of uncorrected tetralogy of Fallot with pulmonary atresia has not been previously reported. We believe our patient's unremitting fever was secondary to the development of necrotizing arteritis, thrombosis, and pulmonary infarction. In patients with pulmonary atresia, ventricular septal defect, and large aortopulmonary collaterals, the development of hypertensive pulmonary artery disease is partly dependent on the patient's age. As patients live longer (if collateral arteries are not stenotic), the likelihood of developing pulmonary vascular disease increases.
Pediatric Cardiology Vol. 13, No. 4, 1992
3.
4.
5.
6.
Acknowledgments. We would like to thank Dr. Maria Colombi, for her help in interpreting the clinical data in the manuscript.
7.
References
8.
1. Haworth S (1980) Collateral arteries in pulmonary atresia with ventricular septal defect: A precarious blood supply. Br Heart J44:5-13 2. Haworth S, Macartney FJ (1980) Growth and development of pulmonary circulation in pulmonary atresia with ventricular
9.
septal defect and major aortopulmonary collateral arteries. Br Heart J 44:14-24 Jefferson K, Rees S, Somerville J (1972) Systemic arterial supply to the lungs in pulmonary atresia and its relation to pulmonary artery development. Br Heart J 34:418-427 Johnson RJ, Sauer U, Buhlmeyer K, Haworth SG (1985) Hypoplasia of the intrapulmonary arteries in children with right ventricular outflow tract obstruction, ventricular septal defect and major aortopulmonary collateral arteries. Pediatr Cardiol 6:137-143 Macartney F, Deverall P, Scott O (1973) Hemodynamic characteristics of systemic arterial blood supply to the lungs. Br Heart J 35:28-37 Macartney FJ, Scott O, Deverall PB (1974) Hemodynamic and anatomical characteristics of pulmonary blood supply in pulmonary atresia with ventricular septal defect--including a case of persistent fifth aortic arch. Br Heart J 36:1049-1060 McGoon MD, Fulton RE, Davis GD, et al (1977) Systemic collateral and pulmonary artery stenosis in patients with congenital pulmonary valve atresia and ventricular septal defect. Circulation 56:473-479 Rabinovitch M, Herrera-deLeon V, Castaneda AR, et al (1981) Growth and development of the pulmonary vascular bed in patients with tetralogy of Fatlot with or without pulmonary atresia. Circulation 64:1234-1249 Wagenvoort CA, Wagenvoort N (1977) Pathology o f pulmonary Hypertension. John Wiley & Sons, New York, pp 56-95, 311-323
Pediatric Cardiology 9 Springer-VerlagNew York Inc. 1992
N e c r o t i z i n g Arteritis in U n c o r r e c t e d T e t r a l o g y o f Fallot with Pulmonary Atresia Jo-Ann Andriko] Max Robinowitz, 3 John Moore, 2 and Renu Virmani 3 Departments of ~Pathology and ZCardiology, Walter Reed Army Medical Center, Washington, D.C. and 3Department of Cardiovascular Pathology, Armed Forces Institute of Pathology, Washington, D.C., USA
SUMMARY. A 10-year-old girl with uncorrected tetralogy of Fallot with pulmonary atresia presented with fevers of unknown origin and left lung infiltrates. At autopsy, necrotizing vascular changes resembling those of severe pulmonary hypertension (grade VI in the HeathEdwards classification) were confined to the left lung. Pulmonary blood flow and pressure were greater in the left lung and were provided by an enlarged collateral artery arising directly from the descending thoracic aorta. To our knowledge, this is the first report of necrotizing arteritis of the pulmonary arteries in uncorrected tetralogy of Fallot with pulmonary atresia. KEY WORDS: Tetralogy of Failot - - Pulmonary hypertension - - Necrotizing arteritis - - Pulmonary atresia with ventricular septal defect
Severe pulmonary hypertension does not occur after corrective surgery for tetralogy of Fallot; however, pulmonary hypertension in patients without corrective surgery may occur. In unoperated patients, pulmonary arterial pressure is modulated by the presence of stenotic segments in the aortopulmonary collateral circulation [1-3, 5, 8]. We present a case of unilateral pulmonary hypertension with fulminant necrotizing arteritis in a patient with uncorrected tetralogy of Fallot with pulmonary atresia (pulmonary atresia with a ventricular septal defect). We propose that the hypertensive changes resulted from increased blood flow through a large aortopulmonary collateral vessel lacking protective stenosis.
Case Report The patient was a 10-year-old white girl with cyanotic congenital heart disease diagnosed at 2 weeks of age. Cardiac catheterization at 2 months and 6 years of age showed a ventricular septal defect, overriding of the aorta (50%), pulmonic atresia and supThe opinions or assertions contained herein are the private views of the authors and are not to be construed as official or reflecting the views of the Department of the Army or the Department of Defense. Address offprint requests to: Dr. Renu Virmani, Department of Cardiovascular Pathology, Armed Forces Institute of Pathology, Washington, D.C. 20306-6000, USA.
ply to the pulmonary circulation by direct collaterals from the descending thoracic aorta, and no evidence of true pulmonary arteries. Selective angiography of her major left lung collateral artery demonstrated a large vessel without stenosis supplying all segments of the left pulmonary vascular bed. Pressure measured in this vessel was equal to aortic pressure (102/67, mean 83 mmHg). Aortography also demonstrated at least two major collaterals, anterior, supplying the right lung. Each of these vessels had significant stenotic segments. Thus, this patient had a left pulmonary vascular bed chronically exposed to high pressure and flows, and a fight pulmonary vascular bed which was protected from these phenomena. It was decided that the patient was inoperable for palliative or corrective surgery, The patient did well with reasonable exercise tolerance until 1 month prior to admission when she developed persistent sore throat and fever unresponsive to oral antibiotics. Blood, urine, and throat cultures were negative. Pulmonary infiltrates in the left lung were present on chest radiographs. On admission, her blood pressure was 126/74 mmHg, her oral temperature 103~ and breath sounds were decreased on the left side. A grade III/VI continuous murmur was heard at the sternum associated with a prominent ventricular heave. The extremities showed clubbing and cyanosis. Laboratory findings were remarkable for a hematocrit of 33%, white blood cell count of 14.7 mm 3, and lactate dehydrogenase of 367 IU/L (normal 0-185 IU/L). Despite institution of broadspectrum antibiotics, she continued to have fever spikes to 103~ and radiographic progression of pneumonia and pleural effusions. A left thoracentesis yielded negative infectious disease cultures. No vegetations were seen on echocardiogram. Ten days after admission the patient complained of poorly localized mid-epigastric pain. Two days later she suddenly collapsed and failed to respond to advanced resuscitative measures.
234
Fig. 1. Sections from the left lung showing muscular pulmonary arteries involved by fibrinoid necrosis of vessel wail with loss of internal elastic lamina. (A) Disruption of the wall with aneurysmal dilatation and intimal fibromuscular proliferation (Movat pentachrome; original magnification, • (B) Early plexiform lesion (Movat pentachrome; original magnification, • (C) Higher power view of vessel wall showing mononuclear and plasma cell inflammation and fibrin deposition (Movat pentachrome; original magnification, x300). (D) Higher power view of vessel wall replaced by granulation tissue (Movat pentachrome; original magnification, x 150).
Pathologic Findings At autopsy, the heart showed a high ventricular septal defect measuring 1.6 cm in diameter, overriding aorta, and right ventricular dilatation and hypertrophy. The pulmonary valve was absent and the main pulmonary artery was a thin cord-like structure measuring 2 mm in external diameter. The right and left pulmonary arteries were markedly hypo-
Pediatric Cardiology Vol. 13, No. 4, 1992
plastic but contained a lumen. The left lung was supplied by a single enlarged aortopulmonary collateral and the right lung by two enlarged aortopulmonary collaterals from the descending thoracic aorta to the hilum of each lung. The diameter of the left collateral measured 1.0 cm and each of the right collaterals measured 0.6 cm. On dissection and serial sectioning, the left collateral was a thin-walled vessel with no segments of stenosis. In contrast, the lumens of both right collaterals were severely stenosed at their origins from the aorta. Gross examination of the lungs showed marked congestion and prominent pulmonary vessels on cut surface. The left lung exhibited multiple nodular areas of fresh parenchymal hemorrhage surrounding pulmonary artery branches which appeared thrombosed. Microscopic examination of the left lung showed multiple hemorrhagic infarcts and markedly dilated arteries containing thrombi in various stages of organization. There was widespread acue inflammation and necrosis of pulmonary arterial walls in association with extensive intraparenchymal hem-
Andriko et al.: Necrotizing Arteritis
Fig. 2. Comparison of muscular pulmonary arteries in the left lung versus the right lung. (A) Well-developed plexiform lesion in left lung (Movat pentachrome; original magnification, x 150). (B) Obliterative fibromuscular intimal proliferation with condensation of elastic fibers in left lung (Movat pentachrome; original magnification, x 150), (C) Thin-walled dilated pulmonary arteries in the subpleural area of the right lung showing an absence of pulmonary hypertensive changes (Movat pentachrome; original magnification, • 150).
orrhage. The small muscular pulmonary arteries and arterioles showed widespread medial hypertrophy and obliterative fibromuscular intimal proliferation with occasional plexiform lesions. Multiple foci of fibrinoid necrosis of the vessel walls (Figs. 1 and 2) were negative for bacteria and fungi. Viral inclusions were not present. The pulmonary arteries and arterioles of the right lung were dilated and thinwalled without vascular changes of pulmonary hypertension or necrotizing arterifis (Fig. 2). Arteritis and intimal proliferation were absent in the other organs.
Discussion
In pulmonary atresia with ventricutar septal defect, patient survival depends on the size and continued patency of the collateral arteries to the lungs. The collateral arteries can be quite large and usually arise directly from the descending thoracic aorta, as in this case, or indirectly from major arterial
235
branches of the aorta (e.g., subclavian or internal mammary arteries) [4, 6, 8]. Intrapulmonary arteries often vary greatly in size and can be quite large distal to the systemic-pulmonary anastomosis [6]. Stenosis of major aortopulmonary collaterals is a well-described feature since the first angiographic report by Jefferson et al. in 1972 [3]. Later reports documented that the stenosis of the collaterals prevents the full transmission of blood flow and pressure from the systemic to pulmonary vasculature [7]. These constricted segments can occur at the origin of collateral from the aorta, along their course, or at anastomoses with pulmonary arteries [1, 2]. Haworth and Macartney [2] in a study of 11 cases of pulmonary atresia with ventricular septal defect found stenosed segments in 58.8% of collaterals with all patients having at least one stenosed vessel. In a radiographic study, 42% of collateral arteries arising from the aorta were stenosed, the most common location being the junction of the collateral with the hilar pulmonary artery [4]. Microscopically, intimal proliferation is the major finding varying in extent from a small area to large intimal cushions which virtually obliterate the vessel lumina [1, 2]. An aortopulmonary anastomosis without a stenosis may result in severe pulmonary vascular changes; Haworth and Macartney [2] and Jefferson et al. [3] describe this as rare occurrences in their series. Necrotizing arteritis is a feature of end-stage pulmonary hypertension associated with large congenital left-to-right shunts and can occur in tetralogy of Fallot following systemic to pulmonary
236
anastomosis operations [9]. Necrotizing arteritis in the setting of uncorrected tetralogy of Fallot with pulmonary atresia has not been previously reported. We believe our patient's unremitting fever was secondary to the development of necrotizing arteritis, thrombosis, and pulmonary infarction. In patients with pulmonary atresia, ventricular septal defect, and large aortopulmonary collaterals, the development of hypertensive pulmonary artery disease is partly dependent on the patient's age. As patients live longer (if collateral arteries are not stenotic), the likelihood of developing pulmonary vascular disease increases.
Pediatric Cardiology Vol. 13, No. 4, 1992
3.
4.
5.
6.
Acknowledgments. We would like to thank Dr. Maria Colombi, for her help in interpreting the clinical data in the manuscript.
7.
References
8.
1. Haworth S (1980) Collateral arteries in pulmonary atresia with ventricular septal defect: A precarious blood supply. Br Heart J44:5-13 2. Haworth S, Macartney FJ (1980) Growth and development of pulmonary circulation in pulmonary atresia with ventricular
9.
septal defect and major aortopulmonary collateral arteries. Br Heart J 44:14-24 Jefferson K, Rees S, Somerville J (1972) Systemic arterial supply to the lungs in pulmonary atresia and its relation to pulmonary artery development. Br Heart J 34:418-427 Johnson RJ, Sauer U, Buhlmeyer K, Haworth SG (1985) Hypoplasia of the intrapulmonary arteries in children with right ventricular outflow tract obstruction, ventricular septal defect and major aortopulmonary collateral arteries. Pediatr Cardiol 6:137-143 Macartney F, Deverall P, Scott O (1973) Hemodynamic characteristics of systemic arterial blood supply to the lungs. Br Heart J 35:28-37 Macartney FJ, Scott O, Deverall PB (1974) Hemodynamic and anatomical characteristics of pulmonary blood supply in pulmonary atresia with ventricular septal defect--including a case of persistent fifth aortic arch. Br Heart J 36:1049-1060 McGoon MD, Fulton RE, Davis GD, et al (1977) Systemic collateral and pulmonary artery stenosis in patients with congenital pulmonary valve atresia and ventricular septal defect. Circulation 56:473-479 Rabinovitch M, Herrera-deLeon V, Castaneda AR, et al (1981) Growth and development of the pulmonary vascular bed in patients with tetralogy of Fatlot with or without pulmonary atresia. Circulation 64:1234-1249 Wagenvoort CA, Wagenvoort N (1977) Pathology o f pulmonary Hypertension. John Wiley & Sons, New York, pp 56-95, 311-323
