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The biological “scrabble” of pulmonary arteriovenous malformations: considerations in the setting of cavopulmonary surgery

Published online by Cambridge University Press:  21 January 2005

Robert M. Freedom ,
Shi-Joon Yoo  and
Donald Perrin
Robert M. Freedom
Affiliation:
The Division of Cardiology, Department of Pediatrics, The Hospital for Sick Children, The University of Toronto Faculty of Medicine, Toronto, Ontario, Canada The Division of Cardiology, Department of Diagnostic Imaging, The Hospital for Sick Children, The University of Toronto Faculty of Medicine, Toronto, Ontario, Canada The Division of Cardiology, Department of Pathology, The Hospital for Sick Children, The University of Toronto Faculty of Medicine, Toronto, Ontario, Canada
Shi-Joon Yoo
Affiliation:
The Division of Cardiology, Department of Diagnostic Imaging, The Hospital for Sick Children, The University of Toronto Faculty of Medicine, Toronto, Ontario, Canada
Donald Perrin
Affiliation:
The Division of Cardiology, Department of Pathology, The Hospital for Sick Children, The University of Toronto Faculty of Medicine, Toronto, Ontario, Canada
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Abstract

Pulmonary arteriovenous fistulas are vascular malformations, which, by virtue of producing abnormal vascular connections proximal to the units of gas exchange, result in intrapulmonary right-to-left shunting. These malformations or fistulas reflect at least in part disordered angiogenesis, and less commonly recruitment and dilation of pre-existing vascular channels.1 Pulmonary arteriovenous fistulas occur in a number of diverse clinical settings. Such fistulas are a well-established feature of the Weber–Osler–Rendu complex, or hereditary haemorrhagic telangiectasia, an autosomal dominant vascular dysplasia characterized by mucocutaneous telangiectasis, epistaxis, gastrointestinal haemorrhage, and arteriovenous malformations in the lung, brain, liver and elsewhere.2,3 They are also seen in the patient with acute or chronic liver disease, disease that is usually but not invariably severe, or those with non-cirrhotic portal hypertension. They may occur as congenital malformations, single or diffuse, large or small in isolation, and when large or extensive enough may result in hypoxaemia, clinical cyanosis, and heart failure.3 Cerebral vascular accidents are also a well-known complication of this disorder.3 An extensive literature has accumulated with regard to the pulmonary arteriovenous fistulas seen in the setting of the Weber–Osler–Rendu complex, and there is considerable information on the genetics, basic biology, clinical findings, complications and therapeutic interventions of these malformations in the setting of this syndrome.4 These issues, however, are not the primary considerations of this review, although some aspects of this fascinating disorder will be discussed later. Rather the focus will be on pulmonary arteriovenous malformations that develop in the setting of cavopulmonary surgery, and their relationship to the pulmonary arteriovenous fistulas occurring in the hepatopulmonary syndrome. The complex tapestry of these overlapping and intersecting clinical observations will be unfolded in the light of their chronology.

Keywords

AngiogenesisGlenn shunthepatopulmonary syndromehereditary haemorrhagic telangiectasiapulmonary arterial hypertension
Type
Continuing Medical Education
Information
Cardiology in the Young , Volume 14 , Issue 4 , August 2004 , pp. 417 - 437
Copyright
© 2004 Cambridge University Press

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References

Marshall B, Duncan BW, Jonas RA. The role of angiogenesis in the development of pulmonary arteriovenous malformations in children after cavopulmonary anastomosis. Cardiology in the Young 1997; 7: 370–374.Google Scholar
Jacobson BS. Hereditary hemorrhagic telangiectasia: a model for blood vessel growth and enlargement. Am J Pathol 2000; 156: 737–742.Google Scholar
Swanson KL, Prakash UBS, Stanson AW. Pulmonary arteriovenous fistulas: the Mayo Clinic experience, 1982–1997. Mayo Clin Proc 1999; 74: 671–680.Google Scholar
Robicsek F. An epitaph for cavopulmonary anastomosis. Ann Thorac Surg 1982; 34: 208–220.Google Scholar
Robicsek F. The history of the right heart bypass before Fontan. Herz 1992; 17: 199–212.Google Scholar
Trusler GA, Williams WG, Cohen AJ, Rabinovitch M, Moes CAF, Smallhorn JF, Coles JG, Lightfoot NE, Freedom RM. William Glenn Lecture: The cavopulmonary shunt. Evolution of a concept. Circulation 1990; 82 (Suppl IV): 131–138.Google Scholar
Castaneda AR. From Glenn to Fontan. A continuing evolution. Circulation 1992; 86: 80–84.Google Scholar
Karl T, Stellin G. Early Italian contribution to cavopulmonary surgery. Ann Thorac Surg 1999; 67: 1175.Google Scholar
Konstantinov IE, Alexi-Meskishvilli A. Cavo-pulmonary shunt: from the first experiments to clinical practice. Ann Thorac Surg 1999; 68: 1100–1106.Google Scholar
Sewell Jr WH, Glenn WWL. Experimental cardiac surgery. I. Observations on the action of a pump designed to shunt the venous blood past the right heart directly into the pulmonary artery. Surgery 1950; 28: 474–481.Google Scholar
Glenn WWL, Patino JF. Circulatory by-pass of the right heart. I. Preliminary observations on the direct delivery of vena caval blood into the pulmonary arterial circulation: azygos vein-pulmonary artery shunt. Yale J Biol Med 1954; 24: 147–149.Google Scholar
Fenn JE, Glenn WW, Guilfoil PH, Hume E, Patino JF. Circulatory by-pass of the right heart. II. Further observations on vena-caval-pulmonary artery shunts. Surg Forum 1955; 6: 189–191.Google Scholar
Glenn WWL. Circulatory bypass of the right side of the heart. IV. Shunt between superior vena cava and distal right pulmonary artery – report of clinical application. N Engl J Med 1958; 259: 117–120.Google Scholar
Carlon CA, Mondini PG, de Marchi R. Surgical treatment of some cardiovascular diseases. J Int Coll Surg 1951; 16: 1–11.Google Scholar
Haller JA, Adkins JC, Rauenhorst J. Total bypass of the superior vena cava into both lungs. Surg Forum 1964; 15: 264–265.Google Scholar
Haller JA, Adkins JC, Worthington M, Rauenhorst J. Experimental studies on permanent bypass of the right heart. Surgery 1966; 59: 1128–1132.Google Scholar
Azzolina G, Eufrate S, Pensa P. Tricuspid atresia: experience in surgical management with a modified cavopulmonary anastomosis. Thorax 1972; 27: 111–115.Google Scholar
Salmon AP, Sethia B, Silove ED, Goh D, Mitchell I, Alton H, de Giovanni JV, Wright JG, Abrams LD. Cavopulmonary anastomosis as long-term palliation for patients with tricuspid atresia. Eur J Cardiothorac Surg 1989; 3: 494–497.Google Scholar
Fontan F, Baudet E. Surgical repair of tricuspid atresia. Thorax 1971; 26: 240–248.Google Scholar
Hopkins RA, Armstrong BE, Serwer GA, Peterson RJ, Oldham Jr HN. Physiological rationale for a bidirectional cavopulmonary shunt. J Thorac Cardiovasc Surg 1985; 90: 391–398.Google Scholar
Bridges ND, Jonas RA, Mayer JE, Flanagan MF, Keane JF, Castaneda AR. Bidirectional cavopulmonary anastomosis as interim palliation for high-risk Fontan candidates. Early results. Circulation 1990; 82 (Suppl 5): IV: 170–176.Google Scholar
Freedom RM, Yoo SJ, Williams WG. The cavopulmonary shunt. In: Freedom RM, Yoo SJ, Mikailian H, Williams WG (eds). The Natural and Modified History of Congenital Heart Disease. Blackwell Publishing Co., Futura Division, Oxford, UK, 2004, pp 435–448.
Bargeron Jr LM, Karp RB, Barcia A, Kirklin JW, Hunt D, Deverall PB. Late deterioration of patients after superior vena cava to right pulmonary artery anastomosis. Am J Cardiol 1972; 30: 211–216.Google Scholar
Cloutier A, Ash JM, Smallhorn JF, Williams WG, Trusler GA, Rowe RD, Rabinovitch M. Abnormal distribution of pulmonary blood flow after the Glenn shunt or Fontan procedure: risk of development of arteriovenous fistulae. Circulation 1985; 72: 471–479.Google Scholar
Freedom RM, Culham JAG, Moes CAF. Angiocardiography of Congenital Heart Disease. Macmillan Publishing Co., New York, 1984, pp 268–270.
Freedom RM, Mawson J, Yoo S-J, Benson LN. Congenital Heart Disease: Textbook of Angiocardiography. Futura Publishing Co., Armonk, NY, 1997, pp 431–492.
Mathur M, Glenn WWL. Long-term evaluation of cava-pulmonary artery anastomosis. Surgery 1973; 74: 899–916.Google Scholar
McFaul RC, Tajik AJ, Mair DD, Danielson GK, Seward JB. Development of pulmonary arteriovenous shunt after superior vena cava-right pulmonary artery (Glenn) anastomosis. Circulation 1977; 55: 212–216.Google Scholar
Laks H, Ardehali A, Grant PW, Permut P, Aharon A, Kuhn M, Isabel-Jones J, Galindo A. Modification of Fontan procedure. Superior vena cava to left pulmonary artery connection and inferior vena cava to right pulmonary artery connection with adjustable atrial septal defect. Circulation 1995; 91: 2943–2947.Google Scholar
Trusler GA, Williams WG. Long-term results of shunt procedures for tricuspid atresia. Ann Thorac Surg 1980; 29: 312–316.Google Scholar
Laks H, Mudd JG, Standeven JW, Fagan L, Willman VL. Long-term effect of the superior vena cava-pulmonary artery anastomosis on pulmonary blood flow. J Thorac Cardiovasc Surg 1977; 74: 253–260.Google Scholar
Kopf GS, Laks H, Stansel HC, Hellenbrand WE, Kleinman CS, Talner NS. Thirty-year follow-up of superior vena cava-pulmonary artery (Glenn) shunts. J Thorac Cardiovasc Surg 1990; 100: 662–671.Google Scholar
Di Carlo D, Williams WG, Freedom RM, Trusler GA. The role of cava-pulmonary (Glenn) anastomosis in the palliative treatment of congenital heart disease. J Thorac Cardiovasc Surg 1982; 83: 437–441.Google Scholar
Yeh Jr T, Williams WG, McCrindle BW, Benson LN, Coles JG, Van Arsdell GS, Webb GG, Freedom RM. Equivalent survival following cavopulmonary shunt: with or without the Fontan procedure. Eur J Cardiothorac Surg 1999; 16: 111–116.Google Scholar
de Leval MR, Kilner P, Gewillig M, Bull C. Total cavopulmonary connection: a logical alternative to atriopulmonary connection for complex Fontan operations. J Thorac Cardiovasc Surg 1988; 96: 682–695.Google Scholar
Vettukattil JJ, Slavik Z, Lamb RK, Monro JL, Keeton BR, Tsang VT, Aldous AJ, Zivanovic A, Johns S, Lewington V, Salmon AP. Intrapulmonary arteriovenous shunting may be a universal phenomenon in patients with the superior cavopulmonary anastomosis: a radionuclide study. Heart 2000; 83: 425–428.Google Scholar
Kim SJ, Bae EJ, Cho DJ, Park IS, Kim YM, Kim WH, Kim SH. Development of pulmonary arteriovenous fistulas after bidirectional cavopulmonary shunt. Ann Thorac Surg 2000; 70: 1918–1922.Google Scholar
Chang R-KR, Alejos JC, Atkinson D, Jensen R, Drant S, Galindo A, Laks H. Bubble contrast echocardiography in detecting pulmonary arteriovenous shunting in children with univentricular heart after cavopulmonary anastomosis. J Am Coll Cardiol 1999; 33: 2052–2058.Google Scholar
Feinstein JA, Moore P, Rosenthal DN, Puchalski M, Brook MM. Comparison of contrast echocardiography versus cardiac catheterization for detection of pulmonary arteriovenous malformations. Am J Cardiol 2002; 89: 281–285.Google Scholar
Samanek M, Oppelt A, Kasalicky J, Voriskova M. Distribution of pulmonary blood flow after cavopulmonary anastomosis (Glenn operation). Br Heart J 1969; 31: 511–516.Google Scholar
Mahle WT, Rychik J, Rome JJ. Clinical significance of pulmonary arteriovenous malformations after staging bidirectional cavopulmonary anastomosis. Am J Cardiol 2000; 86: 239–241.Google Scholar
Bernstein HS, Brook MM, Silverman NH, Bristow J. Development of pulmonary arteriovenous fistulae in children after cavopulmonary shunt. Circulation 1995; 92: II-309–II-314.Google Scholar
Freedom RM, Hamilton R, Yoo SJ, Mikailian H, Benson L, McCrindle B, Justino H, Williams WG. The Fontan procedure: analysis of cohorts and late complications. Cardiology in the Young 2000; 10: 307–331.Google Scholar
Larsson ES, Solymar L, Eriksson BO, de Wahl Granelli A, Mellander M. Bubble contrast echocardiography in detecting pulmonary arteriovenous malformations after modified Fontan operations. Cardiology in the Young 2001; 11: 505–511.Google Scholar
Hansoti RC, Shah NJ. Cirrhosis of liver simulating congenital cyanotic heart disease. Circulation 1966; 33: 71–77.Google Scholar
Laberge J-M, Brandt ML, Lebecque P, Moulin D, Veykemans F, Paradis K, Pelletier L, et al. Reversal of cirrhosis-related pulmonary shunting in two children by orthotopic liver transplantation. Transplantation 1992; 53: 1135–1138.Google Scholar
Fewtrell MS, Noble-Jamieson G, Revell S, Valente J, Friend P, Johnston P, Rasmussen A, Jamieson N, Calne RY, Barnes ND. Intrapulmonary shunting in the biliary atresia/polysplenia syndrome: reversal after liver transplantation. Arch Dis Child 1994; 70: 501–504.Google Scholar
Varela-Fascinetto G, Castaldo P, Fox IJ, Sudan D, Heffron TG, Shaw BW, Langnas AN. Biliary atresia-polysplenia syndrome: surgical and clinical relevance in liver transplantation. Ann Surg 1998; 227: 583–589.Google Scholar
Hopkins WE, Waggoner AD, Barzilai B. Frequency and significance of intrapulmonary right-to-left shunting in end-stage hepatic disease. Am J Cardiol 1992; 70: 516–519.Google Scholar
Barbe T, Losay J, Grimon G, Devictor D, Sardet A, Gauthier F, Houssin D, Bernard O. Pulmonary arteriovenous shunting in children with liver disease. J Pediatr 1995; 126: 571–579.Google Scholar
Kimura T, Hasegawa T, Sasaki T, Okada A, Mushiake S. Rapid progression of intrapulmonary arteriovenous shunting in polysplenia syndrome associated with biliary atresia. Pediatr Pulmonol 2003; 35: 494–498.Google Scholar
Lange PA, Stoller JK. The hepatopulmonary syndrome. Effect of liver transplantation. Clin Chest Med 1996; 17: 115–123.Google Scholar
Stoller JK, Lange PA, Westveer MK, Carey WD, Vogt D, Henderson JM. Prevalence and reversibility of the hepatopulmonary syndrome after liver transplantation. The Cleveland Clinic experience. West J Med 1995; 163: 133–138.Google Scholar
Stoller JK, Moodie D, Schiavone WA, Vogt D, Broughan T, Winkelman E, Rehm PK, Carey WD. Reduction of intrapulmonary shunt and resolution of digital clubbing associated with primary biliary cirrhosis after liver transplantation. Hepatology 1990; 11: 54–58.Google Scholar
Krowka MJ, Cortese DA. Hepatopulmonary syndrome: an evolving perspective in the era of liver transplantation. Hepatology 1990; 11: 138–142.Google Scholar
Fluckiger M. Vorkommen von trommelschagelformigen fingerend phalagen ohne chronische veranderungen der lungen oder am herzen. Wein Med Wehnschr 1884; 49: 1457.Google Scholar
Snell AM. The effects of chronic disease of the liver on the composition and physiochemical properties of blood: changes in the serum proteins; reduction in the oxygen saturation of the arterial blood. Ann Intern Med 1935; 9: 690–671.Google Scholar
Rydell R, Hoffbauer FW. Multiple pulmonary arteriovenous fistulas in juvenile cirrhosis. Am J Med 1956; 21: 450–459.Google Scholar
Berthelot P, Walker JG, Sherlock S, Reid L. Arterial changes in the lungs in cirrhosis of the liver–lung spider nevi. N Engl J Med 1966; 274: 291–298.Google Scholar
Kennedy TC, Knudson RJ. Exercise-aggravated hypoxemia and orthodeoxia in cirrhosis. Chest 1977; 72: 305–309.Google Scholar
Kamata S, Kitayama Y, Usui N, Kuroda S, Nose K, Sawai T, Okada A. Patent ductus venosus with a hypoplastic intrahepatic portal system presenting intrapulmonary shunt: a case treated with banding of the ductus venosus. J Pediatr Surg 2000; 35: 655–657.Google Scholar
Orii T, Ohkohchi N, Kato H, Doi H, Hirano T, Sekiguchi S, Akamatsu Y, Satomi S. Liver transplantation for severe hypoxemia caused by patent ductus venosus. J Pediatr Surg 1997; 32: 1795–1797.Google Scholar
Sugio Y, Shimizu R, Tanaka H, Kondoh O, Sugio Y, Tsukahara M. Diffuse pulmonary arteriovenous fistulae secondary to patent ductus venosus. Eur J Pediatr 2003; 162: 342–343.Google Scholar
Moore JW, Kirby WC, Madden WA, Gaither NS. Development of pulmonary arteriovenous malformations after modified Fontan operations. J Thorac Cardiovasc Surg 1989; 98: 1045–1050.Google Scholar
Jonas RA. Invited letter concerning: the importance of pul-satile flow when systemic venous return is connected directly to the pulmonary arteries. J Thorac Cardiovasc Surg 1993; 105: 173–176.Google Scholar
Srivastava D, Preminger TJ, Lock JE, Mandell V, Keane JF, Mayer Jr JE, Kozakewich H, Spevak PJ. Hepatic venous blood and the development of pulmonary arteriovenous malformations in congenital heart disease. Circulation 1995; 92: 1217–1222.Google Scholar
Kawashima Y, Kitamura S, Matsuda H, Shimazaki Y, Nakano S, Hirose H. Total cavopulmonary shunt operation in complex cardiac anomalies: a new operation. J Thorac Cardiovasc Surg 1984; 87: 74–81.Google Scholar
Kawashima Y, Matsuki O, Yagihara T, Matsuda H. Total cavo-pulmonary shunt operation. Semin Thorac Cardiovasc Surg 1994; 6: 17–20.Google Scholar
Matsuda H, Kawashima Y, Hirose H, Nakano S, Kishimoto H, Sano T. Evaluation of total cavopulmonary shunt operation for single ventricle with common atrioventricular valve and left isomerism. Am J Cardiol 1986; 58: 180–182.Google Scholar
Kawashima Y, Matsuda H, Hirose H, Kitamura S. Total cavopulmonary shunt operation for palliation of complex forms of double inlet right ventricle. In: Anderson RH, Crupi G, Parenzan L (eds). Double Inlet Ventricle. Elsevier Science Publishing Co., Inc., New York, 1987, pp 190–204.
Kawashima Y. Cavopulmonary shunt and pulmonary arteriovenous malformations. Ann Thorac Surg 1997; 63 (4): 930–937.Google Scholar
Kreitmann P, Bourlon F, Jourdan J, Dor V. Surgical treatment of primitive ventricle and complex congenital heart malformation with total exclusion of the right heart: report of a case. J Thorac Cardiovasc Surg 1982; 84: 150.Google Scholar
Shah MJ, Rychik J, Fogel MA, Murphy JD, Jacobs ML. Pulmonary AV malformations after superior cavopulmonary connection: resolution after inclusion of hepaticv veins in the pulmonary circulation. Ann Thorac Surg 1997; 63: 960–963.Google Scholar
Bacha EA, Jonas RA, Mayer Jr JE, Perry S, del Nido PJ. Management of pulmonary arteriovenous malformations after surgery for complex congenital heart disease. J Thorac Cardiovasc Surg 2000; 119: 175–176.Google Scholar
Burch M, Iacovides P, Habibi P, Celermajer D. Non-cardiac cyanosis in left isomerism-report of two cases of multiple pulmonary arteriovenous malformations. Cardiology in the Young 1993; 3: 64–66.Google Scholar
Amodeo A, Di Donato R, Carotti A, Marino B, Marcelletti C. Pulmonary arteriovenous fistulas and polysplenia syndrome (Letter). J Thorac Cardiovasc Surg 1994; 107: 1378–1379.Google Scholar
Kawata H, Kishimoto H, Ikawa S, Ueno T, Nakajima T, Kayatani F, Inamura N, Nakada T. Pulmonary and systemic arteriovenous fistulas in patients with left isomerism. Cardiology in the Young 1998; 8: 290–294.Google Scholar
Hashmi A, Abu-Sulaiman R, McCrindle BW, Smallhorn JF, Williams WG, Freedom RM. Management and outcomes of right atrial isomerism: a 26-year experience. J Am Coll Cardiol 1998; 31: 1120–1126.Google Scholar
Papagiannis J, Kanter RJ, Effman EL, Pratt PC, Marcille R, Browning III IB, Armstrong BE. Polysplenia with pulmonary arteriovenous malformations. Pediatr Cardiol 1993; 14: 127–129.Google Scholar
Alvarez AE, Ribeiro AF, Hessel G, Baracat J, Ribeiro JD. Abernethy malformation: one of the etiologies of hepatopulmonary syndrome. Pediatr Pulmonol 2002; 34: 391–394.Google Scholar
Abernethy J. Account of two instances of uncommon formation in the viscera of the human body. Philos Trans R Soc 1793; 83: 59–66.Google Scholar
McElhinney DB, Marianeschi SM, Reddy VM. Additional pulmonary blood flow with the bidirectional Glenn anastomosis: does it make a difference? Ann Thorac Surg 1998; 66: 668–672.Google Scholar
Bernstein HS, Ursell PC, Brook MM, Hanley FC, Silverman NH, Bristow J. Fulminant development of pulmonary arteriovenous fistulas in an infant after total cavopulmonary shunt. Pediatr Cardiol 1996; 17: 46–50.Google Scholar
Pandurangi UM, Shah MJ, Murali R, Cherian KM. Rapid onset of pulmonary arteriovenous malformations after cavopulmonary anastomosis. Ann Thorac surg 1999; 68: 237–239.Google Scholar
Ovaert C, Filippini LH, Benson LM, Freedom RM. ‘You didn't see them, but now you do!’: use of balloon occlusion angiography in the identification of systemic venous anomalies before and after cavopulmonary procedures. Cardiology in the Young 1999; 9: 357–363.Google Scholar
Anabtawi IN, Ellison RG, Ellison LT. Pulmonary arteriovenous aneurysm and fistulas: anatomical variations, embryology and classification. Ann Thorac Surg 1965; 1: 277–285.Google Scholar
Ofoe VD, Pratap U, Slavik Z. Rapid onset of intrapulmonary arteriovenous shunting after surgical repair of tetralogy of Fallot with pulmonary atresia. Cardiology in the Young 2001; 11: 236–239.Google Scholar
Knight WB, Mee RBB. A cure for pulmonary arteriovenous fistulas. Ann Thorac Surg 1995; 59: 999–1001.Google Scholar
Uemura H, Yagihara T, Hattori R, Kawahira Y, Tsukano S, Watanabe K. Redirection of hepatic venous drainage after total cavopulmonary shunt in left isomerism. Ann Thorac Surg 1999; 68: 1731–1735.Google Scholar
Justino H, Benson LN, Freedom RM. Development of unilateral pulmonary arteriovenous malformations due to unequal distribution of hepatic venous flow. Circulation 2001; 103: E39–E40.Google Scholar
Baskett RJ, Ross DB, Warren AE, Sharratt GP, Murphy DA. Hepatic vein to the azygous vein anastomosis for pulmonary arteriovenous fistulae. Ann Thorac Surg 1999; 68: 232–233.Google Scholar
Steinberg J, Alfieris GM, Brandt III B, Smith F, Byrum CJ, Fink GW, Halter J. New approach to the surgical management of pulmonary arteriovenous malformations after cavopulmonary anastomosis. Ann Thorac Surg 2003; 75: 1640–1642.Google Scholar
Graham K, Sondheimer H, Schaffer M. Resolution of cavopulmonary shunt-associated pulmonary arteriovenous malformation after heart transplantation. J Heart Lung Transplant 1997; 16: 1271–1274.Google Scholar
Lee J, Menkis AH, Rosenberg HC. Reversal of pulmonary arteriovenous malformation after diversion of anomalous hepatic drainage. Ann Thorac Surg 1998; 65: 848–849.Google Scholar
Johnson TR, Schamberger MS, Brown JW, Girod DA. Resolution of acquired pulmonary arteriovenous malformations in a patient with total anomalous systemic venous return. Pediatr Cardiol 2002; 23: 210–212.Google Scholar
Gatzoulis MA, Shinebourne EA, Redington AN, Rigby ML, Ho SY, Shore DF. Increasing cyanosis after cavopulmonary connection caused by abnormal systemic venous channels. Br Heart J 1995; 73: 182–186.Google Scholar
Magee AG, McCrindle BW, Mawson J, Benson LN, Williams WG, Freedom RM. Systemic venous collateral development after the bidirectional cavopulmonary anastomosis. Prevalence and predictors. J Am Coll Cardiol 1998; 32: 502–508.Google Scholar
McElhinney DB, Reddy VM, Hanley FL, Moore P. Systemic venous collateral channels causing desaturation after bidirectional cavopulmonary anastomosis: evaluation and management. J Am Coll Cardiol 1997; 30: 817–824.Google Scholar
Weber HS. Incidence and predictors for the development of significant supradiaphragmatic decompressing venous collateral channels following creation of Fontan physiology. Cardiology in the Young 2001; 11: 289–294.Google Scholar
Sugiyama H, Yoo S-J, Williams W, Benson LN. Characterization and treatment of systemic venous to pulmonary venous collaterals seen after the Fontan operation. Cardiology in the Young 2003; 13: 424–430.Google Scholar
Filippini LHPM, Ovaert C, Nykanen DG, Freedom RM. Reopening of persistent left superior caval vein after bidirectional cavopulmonary connections. Heart 1998; 79: 509–512.Google Scholar
Trivedi KR, Freedom RM, Yoo SJ, McCrindle BW, Benson LN. Physiological impact and transcatheter treatment of the persisting left superior caval vein. Cardiology in the Young 2002; 12: 218–223.Google Scholar
Heinemann M, Breuer J, Steger V, Steil E, Sieverding L, Ziemer G. Incidence and impact of systemic venous collateral development after Glenn and Fontan procedures. Cardiovasc Surg 2001; 49: 172–178.Google Scholar
Rumisek JD, Pigott JD, Weinberg PM, Norwood WI. Coronary sinus septal defect associated with tricuspid atresia. J Thorac Cardiovasc Surg 1986; 92: 142–145.Google Scholar
Westerman GR, Readinger RI, Van Devanter SH. Unusual interatrial communication after the Fontan procedure. J Thorac Cardiovasc Surg 1985; 90: 627–630.Google Scholar
Hsu HS, Nykanen DG, Williams WG, Freedom RM, Benson LN. Right to left interatrial communications after the modified Fontan procedure: identification and management with transcatheter occlusion. Br Heart J 1995; 74: 548–552.Google Scholar
Hayes AM, Burrows PE, Benson LN. An unusual cause of cyanosis after the modified Fontan procedure – closure of venous communications between the coronary sinus and left atrium by transcatheter techniques. Cardiology in the Young 1994; 4: 172–174.Google Scholar
Uemura H, Yagihara T, Monta O. Right-to-left shunt through the cardiac veins after the Fontan procedure. Cardiology in the Young 2000; 10: 416–418.Google Scholar
von Ludinghausen M, Ohmachi N, Besch S, Mettenleiter A. Atrial veins of the human heart. Clin Anat 1995; 8: 169–189.Google Scholar
Chauvin M, Shah DC, Haissaguerre M, Marcellin L, Brechenmacher C. The anatomic basis of connections between the coronary sinus musculature and the left atrium in humans. Circulation 2000; 101: 647–652.Google Scholar
Jacobs ML, Norwood WI. Fontan operation: influence of modifications on morbidity and mortality. Ann Thorac Surg 1994; 58: 945–951, discussion 951–952.Google Scholar
Reed MK, Leonard SR, Zellers TM, Nikaidoh H. Major intrahepatic venovenous fistulas after a modified Fontan operation. Ann Thorac Surg 1996; 61: 713–715.Google Scholar
Fernandez-Martorell P, Sklansky MS, Lucas VW, Kashani IA, Cocalis MW, Jamieson SW, Rothman A. Accessory hepatic vein to pulmonary venous atrium as a cause of cyanosis after the Fontan operation. Am J Cardiol 1996; 77: 1386–1387.Google Scholar
Szkutnik M, Bialkowski J, Knapik P. Major intrahepatic venovenous fistula after modified Fontan operation treated by transcatheter implantation of Amplatzer septal occluder. Cardiology in the Young 2001; 11: 357–360.Google Scholar
Giamberti A, Anderson RH, de Leval MR. Intrahepatic right-to-left shunting after the Fontan operation. Cardiology in the Young 2002; 12: 308–310.Google Scholar
Nomura F, Finucane K, Kerr AR. Rare venous connection causes severe cyanosis after the Fontan operation. Ann Thorac Surg 2001; 72: 2127–2128.Google Scholar
Yoshimura N, Yamaguchi M, Oshima Y, Tei T, Ogawa K. Intrahepatic venovenous shunting to an accessory hepatic vein after Fontan type operation. Ann Thorac Surg 1999; 6: 1494–1496.Google Scholar
Yoshii S, Suzuki S, Osawa H, Hosaka S, Honda Y, Abraham SJ, Tada Y, Sugiyama H, Tan T, Kadono T, Hoshiai M, Komai T. Accessory hepatic vein complicating extra-cardiac total cavopulmonary connection. Ann Thorac Cardiovasc Surg 2002; 8: 112–114.Google Scholar
Kiraly L, Deanfield JE, de Leval MR. Left-sided hepatic vein connected to the coronary sinus. Cardiology in the Young 1996; 6: 190–192.Google Scholar
Ricci M, Rosenkranz ER. Hepatic venous anomalies complicating total cavopulmonary connection. Tex Heart Inst J 2001; 28: 328–330.Google Scholar
Hishitani T, Ogawa K, Hoshino K, Nakamura Y. Surgical ligation of anomalous hepatic vein in a case of heterotaxy syndrome with massive intrahepatic shunting after modified fontan operation. Pediatr Cardiol 1999; 20: 428–430.Google Scholar
van Den Bogaert-van Heesvelde AM, Derom F, Kunnen M, van Egmond H, Devloo-Blancquaert A. Surgery for arteriovenous fistulas and dilated vessels in the right lung after the Glenn procedure. J Thorac Cardiovasc 1978; 76: 195–197.Google Scholar
Bailey LL, Freedom RM, Fowler RJ, Trusler GA. Nonoperative management of late failure of a Glenn anastomosis. Transvenous wafer occlusion of patent superior vena cava–right atrial junction. J Thorac Cardiovasc Surg 1976; 71: 371–375.Google Scholar
Chen HJ, Wargovich TJ, Mickle JP, Hill JA. Repeat balloon occlusion of a pulmonary arteriovenous fistula following cavopulmonary anastomosis in tetralogy of Fallot. Cathet Cardiovasc Diagn 1993; 28: 238–240.Google Scholar
Hsu DT, Quaegebeur JM, Ing FF, Selber EJ, Lamour JM, Gersony WM. Outcome after the single-stage, nonfenestrated Fontan procedure. Circulation 1997; 96: II-335–II-340.Google Scholar
Thompson LD, Petrossian E, McElhinney DB, Abrikosova NA, Moore P, Reddy VM, Hanley FL. Is it necessary to routinely fenestrate an extracardiac Fontan? J Am Coll Cardiol 1999; 34: 539–544.Google Scholar
Gatzoulis MA, Munk MD, Williams WG, Webb GD. Definitive palliation with cavopulmonary or aortopulmonary shunts for adults with single ventricle physiology. Heart 2000; 83: 51–57.Google Scholar
Glenn WW, Fenn JE. Axillary arteriovenous fistula. A means of supplementing blood flow through a cava-pulmonary artery shunt. Circulation 1972; 46: 1013–1017.Google Scholar
Mitchell IM, Goh DW, Abrams LD. Creation of brachial artery-basilic vein fistula. A supplement to the cavopulmonary shunt. J Thorac Cardiovasc Surg 1989; 98: 214–216.Google Scholar
Gomes AS, Benson L, George B, Laks H. Management of pulmonary arteriovenous fistulas after superior vena cava-right pulmonary artery (Glenn) anastomosis. J Thorac Cardiovasc Surg 1984; 87: 636–639.Google Scholar
Magee A, Sim E, Benson LN, Williams WG, Trusler GA, Freedom RM. Augmentation of pulmonary blood flow using an axillary arteriovenous fistula after a cavopulmonary shunt. J Thorac Cardiovasc Surg 1996; 111: 176–180.Google Scholar
Heath D. Pulmonary vascular disease. In: Haselton PS (ed.). Spencer's Pathology of the Lung, 5th edn. McGraw-Hill, New York, 1996, pp 649–693.
White RI, Mitchell SE, Barth KH, Kaufman SL, Kadir S, Chang R, Terry PB. Angioarchitecture of pulmonary arteriovenous malformations: an important consideration before embolotherapy. Am J Roentgenol 1983; 140: 681–686.Google Scholar
Starnes SL, Duncan BW, Kneebone JM, Fraga CH, States S, Rosenthal GL, Lupinetti FM. Pulmonary microvessel density is a marker of angiogenesis in children after cavopulmonary anastomosis. J Thorac Cardiovasc Surg 2000; 120: 902–907.Google Scholar
Folkman J. Fundamental concepts of the angiogenic process. Curr Mol Med 2003; 3: 643–651.Google Scholar
Bussolino F, Mantovani A, Persico G. Molecular mechanisms of blood vessel formation. Trends Biochem Sci 1997; 22: 251–256.Google Scholar
Marchuk DA, Srinivasan S, Squire TL, Zawistowski JS. Vascular morphogenesis: tales of two syndromes. Hum Mol Genet (England), 2003; 12 (Spec No 1): R97–R112.Google Scholar
Folkman J. Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med 1995; 1: 27–31.Google Scholar
Distler JH, Hirth A, Kurowska-Stolarska M, Gay RE, Gay S, Distler O. Angiogenic and angiostatic factors in the molecular control of angiogenesis. Q J Nucl Med 2003; 47: 149–161.Google Scholar
Folkman J. Tumor angiogenesis: therapeutic implications. N Engl J Med 1971; 285: 1182–1186.Google Scholar
Freedom RM. The Edgar Mannheimer Memorial lecture. From Maude to Claude: the musings of an insomniac in the era of evidence-based medicine. Cardiol Young 1998; 8: 6–32.Google Scholar
Clement B, Musso O, Lietard J, Theret N. Homeostatic control of angiogenesis: A newly identified function of the liver? Hepatology 1999; 29: 621–623.Google Scholar
Starnes SL, Duncan BW, Kneebone JM, Rosenthal GL, Patterson K, Fraga CH, Kilian KM, Mathur SK, Lupinetti FM. Angiogenic proteins in the lungs of children after cavopulmonary anastomosis. J Thorac Cardiovasc Surg 2001; 122: 518–523.Google Scholar
Starnes SL, Duncan BW, Kneebone JM, Rosenthal GL, Jones TK, Grifka RG, Cecchin F, Owens DJ, Fearneyhough C, Lupinetti FM. Vascular endothelial growth factor and basic fibroblast growth factor in children with cyanotic congenital heart disease. J Thorac Cardiovasc Surg 2000; 119: 534–539.Google Scholar
Malhotra SP, Reddy VM, Thelitz S, He YP, Hanley FL, Suleman S, Riemer RK. Cavopulmonary anastomosis induces pulmonary expression of the angiotensin II receptor family. J Thorac Cardiovasc Surg 2002; 123: 655–660.Google Scholar
Malhotra SP, Riemer RK, Thelitz S, He YP, Hanley FL, Reddy VM. Superior cavopulmonary anastomosis suppresses the activity and expression of pulmonary angiotensin-converting enzyme. J Thorac Cardiovasc Surg 2001; 122: 464–469.Google Scholar
Malhotra SP, Riemer RK, Thelitz S, He YP, Hanley FL, Reddy VM. The role of oxidative stress in the development of pulmonary arteriovenous malformations after cavopulmonary anastomosis. J Thorac Cardiovasc Surg 2002; 124: 479–485.Google Scholar
Machado RD, Santos RA, Andrade SP. Mechanisms of angiotensin-(1–7)-induced inhibition of angiogenesis. Am J Physiol Regul Integr Comp Physiol 2001; 280: R994–R1000.Google Scholar
Corvol P, Lamande N, Cruz A, Celerier J, Gasc JM. Inhibition of angiogenesis: a new function for angiotensinogen and des (angiotensin I) angiotensinogen. Curr Hypertens Rep 2003; 5: 149–154.Google Scholar
Machado RD, Santos RA, Andrade SP. Opposing actions of angiotensins on angiogenesis. Life Sci 2000; 66: 67–76.Google Scholar
Mainwaring RD, Lamberti JJ, Carter TL, Moore JW, Nelson JC. Renin, angiotensin II, and the development of effusions following bidirectional Glenn and Fontan procedures. J Card Surg 1995; 10: 111–118.Google Scholar
White JR, Harris RA, Lee SR, Craigon MH, Binley K, Price T, Beard GL, Mundy CR, Naylor S. Genetic amplification of the transcriptional response to hypoxia as a novel means of identifying regulators of angiogenesis. Genomics 2004; 83: 1–8.Google Scholar
Shweiki D, Itin A, Soffer D, Keshet E. Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis. Nature 1992; 359: 843–845.Google Scholar
Knighton DR, Hunt TK, Scheuenstuhl H, Halliday BJ, Werb Z, Banda MJ. Oxygen tension regulates the expression of angiogenesis factor by macrophages. Science 1983; 221: 1283–1285.Google Scholar
Phillips PG, Birnby LM, Narendran A. Hypoxia induces capillary network formation in cultured bovine pulmonary microvessel endothelial cells. Am J Physiol 1995; 268: 789–800.Google Scholar
Battegay EJ. Angiogenesis: mechanistic insights, neovascular diseases, and therapeutic prospects. J Mol Med 1995; 73: 333–346.Google Scholar
Starnes SL, Duncan BW, Fraga CH, Desai SY, Jones TK, Mathur SK, Rosenthal GL, Lupinetti FM. Rat model of pulmonary arteriovenous malformations after right superior cavopulmonary anastomosis. Am J Physiol Heart Circ Physiol 2002; 283: H2151–H2156.Google Scholar
Duncan BW, Desai S. Pulmonary arteriovenous malformations after cavopulmonary anastomosis. Ann Thorac Surg 2003; 76: 1759–1766.Google Scholar
Marneros AG, Olsen BR. The role of collagen-derived proteolytic fragments in angiogenesis. Matrix Biol 2001; 20: 337–345.Google Scholar
Wajih N, Sane DC. Angiostatin selectively inhibits signalling by hepatocyte growth factor in endothelial and smooth muscle cells. Blood 2003; 101: 1857–1863.Google Scholar
Cao Y. Endogenous angiogenesis inhibitors: angiostatin, endostatin, and other proteolytic fragments. Prog Mol Subcell Biol 1998; 20: 161–176.Google Scholar
Lietard J, Theret N, Rehn M, Musso O, Dargere D, Pihlajaniemi T, Clement B. The promoter of the long variant of collagen XVIII, the precursor of endostatin, contains liver-specific regulatory elements. Hepatology 2000; 32: 1377–1385.Google Scholar
Schuppan D, Cramer T, Bauer M, Strefeld T, Hahn EG, Herbst H. Hepatocytes as a source of collagen type XVIII endostatin. Lancet 1998; 352: 879–880.Google Scholar
Funakoshi H, Nakamura T. Hepatocyte growth factor: from diagnosis to clinical applications. Clin Chim Acta 2003; 327: 1–23.Google Scholar
Krowka MJ, Edwards WD. A spectrum of pulmonary vascular pathology in portopulmonary hypertension. Liver Transpl 2000; 6: 241–242.Google Scholar
Edwards BS, Weir EK, Edwards WD, Ludwig J, Dykoski RK, Edwards JE. Coexistent pulmonary and portal hypertension: morphologic and clinical features. J Am Coll Cardiol 1987; 10: 1233–1238.Google Scholar
Budhiraja R, Hassoun PM. Portopulmonary hypertension: a tale of two circulations. Chest 2003; 123: 562–576.Google Scholar
Bernard O. Pulmonary arteriovenous shunting and pulmonary artery hypertension in children with liver disease. Pediatr Pulmonol Suppl 1999; 18: 88–90.Google Scholar
Herve P, Lebrec D, Brenot F, Simonneau G, Humbert M, Sitbon O, Duroux P. Pulmonary vascular disorders in portal hypertension. Eur Respir J 1998; 11: 1153–1166.Google Scholar
Kaymakoglu S, Kahraman T, Kudat H, Demir K, Cakaloglu Y, Adalet I, Dincer D, Besisik F, Boztas G, Sozen AB, Mungan Z, Okten A. Hepatopulmonary syndrome in noncirrhotic portal hypertensive patients. Dig Dis Sci 2003; 48: 556–560.Google Scholar
Castro M, Krowka MJ. Hepatopulmonary syndrome. A pulmonary vascular complication of liver disease. Clin Chest Med 1996; 17: 35–48.Google Scholar
Schraufnagel DE, Kay JM. Structural and pathologic changes in the lung vasculature in chronic liver disease. Clin Chest Med 1996; 17: 1–15.Google Scholar
Hadengue A, Benhayoun MK, Lebrec D, Benhamou JP. Pulmonary hypertension complicating portal hypertension: prevalence and relation to splanchnic hemodynamics. Gastroenterology 1991; 100: 520–528.Google Scholar
Losay J, Piot D, Bougaran J, Ozier Y, Devictor D, Houssin D, Bernard O. Early liver transplantation is crucial in children with liver disease and pulmonary artery hypertension. J Hepatol 1998; 28: 337–342.Google Scholar
Krowka MJ. Hepatopulmonary syndrome versus portopulmonary hypertension: distinctions and dilemmas. Hepatology 1997; 25: 1282–1284.Google Scholar
Tuder RM, Chacon M, Alger L, Wang J, Taraseviciene-Stewart L, Kasahara Y, Cool CD, Bishop AE, Geraci M, Semenza GL, Yacoub M, Polak JM, Voelkel NF. Expression of angiogenesis-related molecules in plexiform lesions in severe pulmonary hypertension: evidence for a process of disordered angiogenesis. J Pathol 2001; 195: 367–374.Google Scholar
Tuder RM, Voelkel NF. Angiogenesis and pulmonary hypertension: a unique process in a unique disease. Antioxid Redox Signal 2002; 4: 833–843.Google Scholar
Rabinovitch M. Pathobiology of pulmonary hypertension. Extra-cellular matrix. Clin Chest Med 2001; 22: 433–449.Google Scholar
Matsubara O, Nakamura T, Uehara T, Kasuga T. Histometrical investigation of the pulmonary artery in severe hepatic disease. J Pathol 1984; 143: 31–37.Google Scholar
Jones FD, Kuo PC, Johnson LB, Njoku MJ, Dixon-Ferguson MK, Plotkin JS. The coexistence of portopulmonary hypertension and hepatopulmonary syndrome. Anesthesiology 1999; 90: 626–629.Google Scholar
Krowka MJ, Mandell MS, Ramsay MA, Kawut SM, Fallon MB, Manzarbeitia C, Pardo M, Marotta P, Uemoto S, Stoffel MP, Benson JT. Hepatopulmonary syndrome and portopulmonary hypertension: A report of the multicenter liver transplant database. Liver Transpl 2004; 10: 174–182.Google Scholar
Mal H, Burgiere O, Durand F, Fartoukh M, Cohen-Solal A, Fournier M. Pulmonary hypertension following hepatopulmonary syndrome in a patient with cirrhosis. J Hepatol (Denmark) 1999; 31: 360–364.Google Scholar
Martinez-Palli G, Barbera JA, Taura P, Cirera I, Visa J, Rodriguez-Roisin R. Severe portopulmonary hypertension after liver transplantation in a patient with preexisting hepatopulmonary syndrome. J Hepatol 1999; 31: 1075–1079.Google Scholar
Kaspar MD, Ramsay MA, Shuey CB, Levy MF, Klintmalm GG. Severe pulmonary hypertension and amelioration of hepatopulmonary syndrome after liver transplantation. Liver Transpl Surg 1998; 4: 177–179.Google Scholar
Liu H, Lee SS. Cardiopulmonary dysfunction in cirrhosis. J Gastroenterol Hepatol 1999; 14: 600–608.Google Scholar
Azuma H. Genetic and molecular pathogenesis of hereditary hemorrhagic telangiectasia. J Med Invest 2000; 47: 81–90.Google Scholar
van den Driesche S, Mummery CL, Westermann CJ. Hereditary hemorrhagic telangiectasia: an update on transforming growth factor beta signaling in vasculogenesis and angiogenesis. Cardiovasc Res 2003; 58: 20–31.Google Scholar
Begbie ME, Wallace GM, Shovlin CL. Hereditary haemorrhagic telangiectasia (Osler–Weber–Rendu syndrome): a view from the 21st century. Postgrad Med J 2003; 79: 18–24.Google Scholar
Haitjema T, Westermann CJ, Overtoom TT, Timmer R, Disch F, Mauser H, Lammers JW. Hereditary hemorrhagic telangiectasia (Osler–Weber–Rendu disease): new insights in pathogenesis, complications, and treatment. Arch Intern Med 1996; 156: 714–719.Google Scholar
Marchuk DA. Genetic abnormalities in hereditary hemorrhagic telangiectasia. Curr Opin Hematol 1998; 5: 332–338.Google Scholar
Sorensen LK, Brooke BS, Li DY, Urness LD. Loss of distinct arterial and venous boundaries in mice lacking endoglin, a vascular-specific TGFbeta coreceptor. Dev Biol 2003; 261: 235–250.Google Scholar
Bourdeau A, Cymerman U, Paquet ME, Meschino W, McKinnon WC, Guttmacher AE, Becker L, Letarte M. Endoglin expression is reduced in normal vessels but still detectable in arteriovenous malformations of patients with hereditary hemorrhagic telangiectasia type 1. Am J Pathol 2000; 156: 911–923.Google Scholar
Jonker L, Arthur HM. Endoglin expression in early development is associated with vasculogenesis and angiogenesis. Mech Dev 2002; 110: 193–196.Google Scholar
Satomi J, Mount RJ, Toporsian M, Paterson AD, Wallace MC, Harrison RV, Letarte M. Cerebral vascular abnormalities in a murine model of hereditary hemorrhagic telangiectasia. Stroke 2003; 34: 783–789.Google Scholar
Bourdeau A, Faughnan ME, Letarte M. Endoglin-deficient mice, a unique model to study hereditary hemorrhagic telangiectasia. Trends Cardiovasc Med 2000; 10: 279–285.Google Scholar
McDonald JE, Miller FJ, Hallam SE, Nelson L, Marchuk DA, Ward KJ. Clinical manifestations in a large hereditary hemorrhagic telangiectasia (HHT) type 2 kindred. Am J Med Genet 2000; 93: 320–327.Google Scholar
Abdalla SA, Geisthoff UW, Bonneau D, Plauchu H, McDonald J, Kennedy S, Faughnan ME, Letarte M. Visceral manifestations in hereditary haemorrhagic telangiectasia type 2. J Med Genet 2003, 40: 494–502.Google Scholar
Kjeldsen AD, Brusgaard K, Poulsen L, Kruse T, Rasmussen K, Green A, Vase P. Mutations in the ALK-1 gene and the phenotype of hereditary hemorrhagic telangiectasia in two large Danish families. Am J Med Genet 2001; 98: 298–302.Google Scholar
Seki T, Yun J, Oh SP. Arterial endothelium-specific activin receptor-like kinase 1 expression suggests its role in arterialization and vascular remodeling. Circ Res 2003; 93: 682–689.Google Scholar
Oh SP, Seki T, Goss KA, Imamura T, Yi Y, Donahoe PK, Li L, Miyazono K, ten Dijke P, Kim S, Li E. Activin receptor-like kinase 1 modulates transforming growth factor-beta 1 signaling in the regulation of angiogenesis. Proc Natl Acad Sci USA 2000; 97: 2626–2631.Google Scholar
Bourdeau A, Faughnan ME, McDonald ML, Paterson AD, Wanless IR, Letarte M. Potential role of modifier genes influencing transforming growth factor-beta1 levels in the development of vascular defects in endoglin heterozygous mice with hereditary hemorrhagic telangiectasia. Am J Pathol 2001; 158: 2011–2020.Google Scholar
Berg JN, Gallione CJ, Stenzel TT, Johnson DW, Allen WP, Schwartz CE, Jackson CE, Porteous ME, Marchuk DA. The activin receptor-like kinase 1 gene: genomic structure and mutations in hereditary hemorrhagic telangiectasia type 2. Am J Hum Genet 1997; 61: 60–67.Google Scholar
Torsney E, Charlton R, Diamond AG, Burn J, Soames JV, Arthur HM. Mouse model for hereditary hemorrhagic telangiectasia has a generalized vascular abnormality. Circulation 2003; 107: 1653–1657.Google Scholar
Berg JN, Guttmacher AE, Marchuk DA, Porteous ME. Clinical heterogeneity in hereditary haemorrhagic telangiectasia: are pulmonary arteriovenous malformations more common in families linked to endoglin? J Med Genet 1996; 33: 256–257.Google Scholar
Trembath RC, Thomson JR, Machado RD, Morgan NV, Atkinson C, Winship I, Simonneau G, Galie N, Loyd JE, Humbert M, Nichols WC, Morrell NW, Berg J, Manes A, McGaughran J, Pauciulo M, Wheeler L. Clinical and molecular genetic features of pulmonary hypertension in patients with hereditary hemorrhagic telangiectasia. N Engl J Med 2001; 345: 325–334.Google Scholar
Sapru RP, Hutchison DC, Hall JI. Pulmonary hypertension in patients with pulmonary arteriovenous fistulae. Br Heart J 1969; 31: 559–569.Google Scholar
Trell E, Johansson BW, Linell F, Ripa J. Familial pulmonary hypertension and multiple abnormalities of large systemic arteries in Osler's disease. Am J Med 1972; 124: 50–63.Google Scholar
Humbert M, Trembath RC. Genetics of pulmonary hypertension: from bench to bedside. Eur Respir J 2002; 20: 741–749.Google Scholar
Rudarakanchana N, Flanagan JA, Chen H, Upton PD, Machado R, Patel D, Trembath RC, Morrell NW. Functional analysis of bone morphogenetic protein type II receptor mutations underlying primary pulmonary hypertension. Hum Mol Genet 2002; 11: 1517–1525.Google Scholar
Newman JH, Wheeler L, Lane KB, Loyd E, Gaddipati R, Phillips JA, Loyd JE. Mutation in the gene for bone morphogenetic protein receptor II as a cause of primary pulmonary hypertension in a large kindred. N Engl J Med 2001; 345: 319–324.Google Scholar
Trembath RC, Harrison R. Insights into the genetic and molecular basis of primary pulmonary hypertension. Pediatr Res 2003; 53: 883–888.Google Scholar
Nichols WC, Koller DL, Slovis B, Foroud T, Terry VH, Arnold ND, Siemieniak DR, Wheeler L, Phillips JA, Newman JH, Conneally PM, Ginsburg D, Loyd JE. Localization of the gene for familial primary pulmonary hypertension to chromosome 2q31-32. Nat Genet 1997; 15: 277–280.Google Scholar
Rindermann M, Grunig E, von Hippel A, Koehler R, Miltenberger-Miltenyi G, Mereles D, Arnold K, Pauciulo M, Nichols W, Olschewski H, Hoeper MM, Winkler J, Katus HA, Kubler W, Bartram CR, Janssen B. Primary pulmonary hypertension may be a heterogeneous disease with a second locus on chromosome 2q31. J Am Coll Cardiol 2003; 41: 2237–2244.Google Scholar
Morse JH. Bone morphogenetic protein receptor 2 mutations in pulmonary hypertension. Chest 2002; 121 (Suppl 3): 50S–53S.Google Scholar
Lane KB, Machado RD, Pauciulo MW, Thomson JR, Phillips JA, Loyd JE, Nichols WC, Trembath RC. Heterozygous germline mutations in BMPR2, encoding a TGF-beta receptor, cause familial primary pulmonary hypertension. The International PPH Consortium. Nat Genet 2000; 26: 81–84.Google Scholar
Atkinson C, Stewart S, Upton PD, Machado R, Thomson JR, Trembath RC, Morrell NW. Primary pulmonary hypertension is associated with reduced pulmonary vascular expression of type II bone morphogenetic protein receptor. Circulation 2002; 105: 1672–1678.Google Scholar
Harrison RE, Flanagan JA, Sankelo M, Abdalla SA, Rowell J, Machado RD, Elliott CG, Robbins IM, Olschewski H, McLaughlin V, Gruenig E, Kermeen F, Laitinen T, Morrell NW, Trembath RC, Halme M, Raisanen-Sokolowski A. Molecular and functional analysis identifies ALK-1 as the predominant cause of pulmonary hypertension related to hereditary haemorrhagic telangiectasia. J Med Genet 2003; 40: 865–871.Google Scholar
Loscalzo J. Genetic clues to the cause of pulmonary hypertension. N Engl J Med 2001; 345: 367–371.Google Scholar
Loscalzo J. The evolution of the discipline of vascular biology: from systems physiology to molecular biology to molecular systems. Circ Res 2003; 93: 583–585.Google Scholar
Klima U, Peters T, Peuster M, Hausdorf G, Haverich A. A novel technique for establishing total cavopulmonary connection: from surgical preconditioning to interventional completion. J Thorac Cardiovasc Surg 2000; 120: 1007–1009.Google Scholar