Congenital Heart Disease: Pathology, Natural History, and Interventions

Cardiovascular Pathology: Fourth Edition

Volumn , Issue , 2016, Pages 611-647

  Ottaviani, G ^a,b   Buja, L Maximilian ^c  

^a UNIVERSITY OF TEXAS   (United States)

^b UNIVERSITY OF MILAN   (Italy)

^c UNIVERSITY OF TEXAS MEDICAL SCHOOL   (United States)

Author keywords

Cardiovascular development; Clinical features; Congenital heart disease; Interventions; Natural history; Pathology; Transcription factors

Indexed keywords

EID: 85007578774     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1016/B978-0-12-420219-1.00014-8     Document Type: Chapter

References (110)

1. Abbott M.E. Atlas of congenital cardiac disease 2006, McGill-Queen's University Press, Montreal and Kingston, [First published in 1936 by the American Heart Association].
2. Fraser R. Maude Abbott and the "atlas of congenital cardiac disease". Cardiovasc Pathol 2006, 15:233-235.
3. Edwards J.E. Congenital malformations of the heart and great vessels. Pathology of the heart and blood vessels 1968, 262-278. Charles C. Thomas, Springfield, IL. 3rd ed. S.E. Gould (Ed.).
4. Edwards J.E., Carey L.S., Neufeld H.N., Lester R.G. Congenital heart disease: correlation of pathologic anatomy and angiocardiography 1965, vols. I and II. WB Saunders Co, Philadelphia.
5. Bharati S., Lev M. The pathology of congenital heart disease: a personal experience with more than 6,300 congenitally malformed hearts 1996, vols. I and II. Future Publishing Co, Armonk, NY.
6. Titus J.L., Edwards J.E. Anatomic abnormalities. Section II. Congenital heart disease in the adult. Cardiovascular medicine 2000, 147-178. Churchill Livingstone, Philadelphia. 2nd ed. J.T. Willerson, J.N. Cohn (Eds.).
7. Anderson R.H., Becker A.E. Normal and abnormal anatomy. Section II. Congenital heart disease in the adult. Cardiovascular medicine 2007, 205-232. Springer-Verlag, London. 3rd ed. J.T. Willerson, J.N. Cohn, H.J.J. Wellens, D.R. Holmes (Eds.).
8. Van Praagh R. The first Stella van Praagh memorial lecture: the history and anatomy of tetralogy of Fallot. Semin Thorac Cardiovasc Surg Pediatr Card Surg Annu 2009, 12:19-38.
9. Jacobs M.L., Jacobs J.P. The early history of surgery for patients with tetralogy of Fallot. Cardiol Young 2008, 18(Suppl. 3):8-11.
10. Neish S.R., Towbin J.A. Pathophysiology, clinical recognition, and treatment of congenital heart disease. Cardiovascular medicine 2007, 233-277. Springer-Verlag, London. 3rd ed. J.T. Willerson, J.N. Cohn, H.J.J. Wellens, D.R. Holmes (Eds.).
11. Brown D.W., Fulton D.R. Congenital heart disease in children and adolescents. Hurst's the heart 2011, 1827-1883. McGraw Hill Medical, New York. 13th ed. V. Fuster, R.A. Walsh, R.A. Harrington (Eds.).
12. Webb G.D., Smallhorn J.F., Therrien J., Redington A.N. Congenital heart disease. Braunwald's heart disease: a textbook of cardiovascular medicine 2012, 1411-1467. Elsevier, Philadelphia. 9th ed. R.O. Bonow, D.L. Mann, D.P. Zipes, P. Libby (Eds.).
13. Schoen F.J., Mitchell R.N. The heart. Robbins and Cotran-pathologic basis of disease 2014, 531-538. Saunders, Elsevier Inc, Philadelphia. 9th ed. V. Kumar, A.K. Abbas, J.C. Aster (Eds.).
14. Go A.S., Mozaffarian D., Roger V.L., Benjamin E.J., Berry J.D., Blaha M.J., et al. Heart disease and stroke statistics-2014 update: a report from the American Heart Association. Circulation 2014, 129:e28-e292.
15. van der Linde D., Konings E.E., Slager M.A., Witsenburg M., Helbing W.A., Takkenberg J.J., et al. Birth prevalence of congenital heart disease worldwide: a systematic review and meta-analysis. J Am Coll Cardiol 2011, 58:2241-2247.
16. Ottaviani G. Crib death-sudden infant death syndrome (SIDS): sudden infant and perinatal unexplained death: the pathologist's viewpoint 2014, Springer International Publishing, Heidelberg. 2nd ed.
17. Hoffman J.I., Kaplan S. The incidence of congenital heart disease. J Am Coll Cardiol 2002, 39:1890-1900.
18. Hoffman J.I., Kaplan S., Liberthson R.R. Prevalence of congenital heart disease. Am Heart J 2004, 147:425-439.
19. Fixler D.E., Xu P., Nembhard W.N., Ethen M.K., Canfield M.A. Age at referral and mortality from critical congenital heart disease. Pediatrics 2014, 134:e98-e105.
20. Marian A.J., Brugada R., Roberts R. Cardiovascular diseases caused by genetic abnormalities. Hurst's the heart 2011, 1783-1826. McGraw Hill Medical, New York. 13th ed. V. Fuster, R.A. Walsh, R.A. Harrington (Eds.).
21. Milewicz D. Genetic aspects of congenital heart disease. Cardiovascular medicine 2007, 2599-2605. Springer-Verlag, London. 3rd ed. J.T. Willerson, J.N. Cohn, H.J.J. Wellens, D.R. Holmes (Eds.).
22. Egbe A., Lee S., Ho D., Uppu S., Srivastava S. Prevalence of congenital anomalies in newborns with congenital heart disease diagnosis. Ann Pediatr Cardiol 2014, 7:86-91.
23. Nemer M. Genetic insights into normal and abnormal heart development. Cardiovasc Pathol 2008, 17:48-54.
24. Donofrio M.T., Moon-Grady A.J., Hornberger L.K., Copel J.A., Sklansky M.S., Abuhamad A., et al. Diagnosis and treatment of fetal cardiac disease: a scientific statement of the American Heart Association. Circulation 2014, 129:2183-2242.
25. Srivastava D. Making or breaking the heart: from lineage determination to morphogenesis. Cell 2006, 126:1037-1048.
26. Ransom J., Srivastava D. The genetics of cardiac birth defects. Semin Cell Dev Biol 2007, 18:132-139.
27. Schneider M.D., Olson E.N. Toward a molecular basis for congenital heart disease. Cardiovascular medicine 2007, 1135-1156. Springer-Verlag, London. 3rd ed. J.T. Willerson, J.N. Cohn, H.J.J. Wellens, D.R. Holmes (Eds.).
28. Jing-Bin H., Ying-Long L., Pei-Wu S., Xiao-Dong L., Ming D., Xiang-Ming F. Molecular mechanisms of congenital heart disease. Cardiovasc Pathol 2010, 19:e183-e198.
29. Rana M.S., Christoffels V.M., Moorman A.F. A molecular and genetic outline of cardiac morphogenesis. Acta Physiol (Oxf) 2013, 207:588-615.
30. Li J., Liu W.D., Yang Z.L., Yuan F., Xu L., Li R.G., et al. Prevalence and spectrum of GATA4 mutations associated with sporadic dilated cardiomyopathy. Gene 2014, 548:174-181.
31. Buja L.M. Anatomy of the heart. Cardiovascular medicine 2007, 3-17. Springer-Verlag, London. 3rd ed. J.T. Willerson, J.N. Cohn, H.J.J. Wellens, D.R. Holmes (Eds.).
32. Colborn G.L., Weidman T.A., Symbas P., Skandalakis P.N. Pericardium, heart, great vessels in the thorax. Skandalakis surgical anatomy: the embryologic and anatomic basis of modern surgery 2004, 303-351. Paschalidis Medical Publications, Athens. J.E. Skandalakis, G.L. Colborn (Eds.).
33. Majesky M.W. Developmental basis of vascular smooth muscle diversity. Arterioscler Thromb Vasc Biol 2007, 27:1248-1258.
34. Morse D.E. Embryology, anatomy, and histology of the aorta. The aorta 1979, 15-37. Grene and Stratton, New York. J. Lindsay, J.W. Hurst (Eds.).
35. Pfaltzgraff E.R., Shelton E.L., Galindo C.L., et al. Embryonic domains of the aorta derived from diverse origins exhibit distinct properties that converge into a common phenotype in the adult. J Mol Cell Cardiol 2014, 69:88-96.
36. Hines M.H. Neonatal cardiovascular physiology. Semin Pediatr Surg 2013, 22:174-178.
37. Orme N.M., Miller D.V., Edwards W.D. Age-related changes among 25 patients with congenital cardiac left-to-right shunts and irreversible plexogenic pulmonary arteriopathy. Cardiovasc Pathol 2008, 17:382-391.
38. Brugada J., Blom N., Sarquella-Brugada G., Blomstrom-Lundqvist C., Deanfield J., Janousek J., et al. Pharmacological and non-pharmacological therapy for arrhythmias in the pediatric population: EHRA and AEPC-Arrhythmia Working Group joint consensus statement. Europace 2013, 15:1337-1382.
39. World Health Organization. International classification of diseases. 10th revision (ICD-10). Available from: (accessed October 29, 2014). http://apps.who.int/classifications/icd10/browse/2010/en#/Q20-Q28.
40. Thiene G., Frescura C. Anatomical and pathophysiological classification of congenital heart disease. Cardiovasc Pathol 2010, 19:259-274.
41. Ware A.L., Miller D.V., Porter C.J., Edwards W.E. Characterization of atrial morphology and sinus node morphology in heterotaxy syndrome: an autopsy based study of 41 cases (1950-2008). Cardiovasc Pathol 2012, 21:421-427.
42. Anderson R.H., Brown N.A., Meno C., Spicer D.E. The importance of being isomeric. Clin Anat 2015, 28:477-486.
43. Fallot E.L.A. Contribution à l'anatomie pathologique de la maladie bleue (cyanose cardiaque). Mars Med 1888, 25:77-93.
44. Edwards W.D. Congenital heart disease. Anderson's pathology 1996, 1339-1396. Mosby, St. Louis. 10th ed. I. Damjanov, J. Linder (Eds.).
45. Schoen F.J., Edwards W.D. Pathology of cardiovascular interventions, including endovascular therapies, revascularization, vascular replacement, cardiac assist/replacement, arrhythmia control, and repaired congenital heart disease. Cardiovascular pathology 2001, 678-724. Churchill Livingstone, New York. 3rd ed. M.D. Silver, A.I. Gotlieb, F.J. Schoen (Eds.).
46. Sabate Rotes A., Eidem B.W., Connolly H.M., Bonnichsen C.R., Rosedahl J.K., Schaff H.V., et al. Long-term follow-up after pulmonary valve replacement in repaired tetralogy of Fallot. Am J Cardiol 2014, 114:901-908.
47. Villafañe J., Lantin-Hermoso M.R., Bhatt A.B., Tweddell J.S., Geva T., Nathan M. D-transposition of the great arteries: the current era of the arterial switch operation. J Am Coll Cardiol 2014, 64:498-511.
48. Hornung T.S., Calder L. Congenitally corrected transposition of the great arteries. Heart 2010, 96:1154-1161.
49. Kreutzer C., Kreutzer J., Kreutzer G.O. Reflections on five decades of the Fontan Kreutzer procedure. Front Pediatr 2013, 1:45.
50. Said S.M., Burkhart H.M., Schaff H.V., Cetta F., Driscoll D.J., Li Z., et al. Fontan conversion: identifying the high-risk patient. Ann Thorac Surg 2014, 97:2115-2121.
51. Collett R.W., Edwards J.E. Persistent truncus arteriosus: a classification according to anatomic types. Surg Clin North Am 1949, 29:1245-1270.
52. Van Praagh R., Van Praagh S. The anatomy of common aorticopulmonary trunk (truncus arteriosus communis) and its embryologic implications. A study of 57 necropsy cases. Am J Cardiol 1965, 16:406-425.
53. O'Byrne M.L., Mercer-Rosa L., Zhao H., Zhang X., Yang W., Cassedy A., et al. Morbidity in children and adolescents after surgical correction of truncus arteriosus communis. Am Heart J 2013, 166:512-518.
54. Darling R.C., Rothney W.B., Craig J.M. Total pulmonary venous drainage into the right side of the heart: report of 17 autopsied cases not associated with other major cardiovascular anomalies. Lab Invest 1957, 6:44-64.
55. Hoashi T., Kagisaki K., Kurosaki K., Kitano M., Shiraishi I., Ichikawa H. Intrinsic obstruction in pulmonary venous drainage pathway is associated with poor surgical outcomes in patients with total anomalous pulmonary venous connection. Pediatr Cardiol 2015, 36:432-437.
56. Obler D., Juraszek A.L., Smoot L.B., Natowicz M.R. Double outlet right ventricle: aetiologies and associations. J Med Genet 2008, 45:481-497.
57. Lagopoulos M.E., Manlhiot C., McCrindle B.W., Jaeggi E.T., Friedberg M.K., Nield L.E. Impact of prenatal diagnosis and anatomical subtype on outcome in double outlet right ventricle. Am Heart J 2010, 160:692-700.
58. Schwarz F., Blaschczok H.C., Sinzobahamvya N., Sata S., Korn F., Weber A., et al. The Taussig-Bing anomaly: long-term results. Eur J Cardiothorac Surg 2013, 44:821-827.
59. Attenhofer Jost C.F.A., Connolly H.M., Edwards W.E., Hayes D., Warnes C.A., Danielson G.K. Ebstein's anomaly-review of a multifaceted cardiac condition. Swiss Med Wkly 2005, 135:269-281.
60. Attenhofer Jost C.H., Connolly H.M., Dearani J.A., Edwards W.D., Danielson G.K. Ebstein's anomaly. Circulation 2007, 115:277-285.
61. Negoi R.I., Ispas A.T., Ghiorghiu I., Filipoiu F., Negoi I., Hostiuc M., et al. Complex Ebstein's malformation: defining preoperative cardiac anatomy and function. J Card Surg 2013, 28:70-81.
62. Ebstein W. über einen sehr seltenen fall von insufficienz der valvula tricuspidalis, bedingt durch eine angeborene hochgradige Missbildung derselben. Arch Anat Physiol Wissensch Med 1866, 7:238-254.
63. Kobayashi J., Yoshida M., Tarui S., Hirata M., Nagai Y., Kasahara S., et al. Directed differentiation of patient-specific induced pluripotent stem cells identifies the transcriptional repression and epigenetic modification of NKX2-5, HAND1, and NOTCH1 in hypoplastic left heart syndrome. PLoS One 2014, 9:e102796.
64. Lloyd D.F.A., Cutler L., Tibby S.M., Vimalesvaran S., Qureshi S.A., Rosenthal E., et al. Analysis of preoperative condition and interstage mortality in Norwood and hybrid procedures for hypoplastic left heart syndrome using the Aristotle scoring system. Heart 2014, 100:775-780.
65. Pickett C.A., Villines T.C., Ferguson M.A., Hulten E.A. Percutaneous closure versus medical therapy alone for cryptogenic stroke patients with a patent foramen ovale: meta-analysis of randomized controlled trials. Tex Heart Inst J 2014, 41:357-367.
66. Geva T., Martins J.D., Wald R.M. Atrial septal defects. Lancet 2014, 383:1921-1932.
67. Cuypers J.A., Opi P., Menting M.E., Utens E.M., Witsenburg M., Helbing W.A., et al. The unnatural history of an atrial septal defect: longitudinal 35 year follow up after surgical closure at young age. Heart 2013, 99:1346-1352.
68. Sellmer A., Bjerre J.V., Schmidt M.R., McNamara P.J., Hjortdal V.E., Høst B., et al. Morbidity and mortality in preterm neonates with patent ductus arteriosus on day 3. Arch Dis Child Fetal Neonatal Ed 2013, 98:F505-F510.
69. Weisz D.E., More K., McNamara P.J., Shah P.S. PDA ligation and health outcomes: a meta-analysis. Pediatrics 2014, 133:e1024-e1046.
70. Matsuhisa H., Yoshimura N., Higuma T., Misaki T., Onuma Y., Ichida F., et al. Ventricular septal dysfunction after surgical closure of multiple ventricular septal defects. Ann Thorac Surg 2013, 96:891-897.
71. Bader R.S., Punn R., Silverman N.H. Evaluation of risk factors for prediction of outcome in fetal spectrum of atrioventricular septal defects. Congenit Heart Dis 2014, 9:286-293.
72. St.Louis J.D., Jodhka U., Jacobs J.P., He X., Hill K.D., Pasquali S.K., et al. Contemporary outcomes of complete atrioventricular septal defect repair: analysis of the Society of Thoracic Surgeons Congenital Heart Surgery Database. J Thorac Cardiovasc Surg 2014, 48:2526-2531.
73. Briggs L.E., Kakarla J., Wessels A. The pathogenesis of atrial and atrioventricular septal defects with special emphasis on the role of the dorsal mesenchymal protrusion. Differentiation 2012, 84:117-130.
74. Buratto E., McCrossan B., Galati J.C., Bullock A., Kelly A., d'Udekem Y., et al. Repair of partial atrioventricular septal defect: a 37-year experience. Eur J Cardiothorac Surg 2015, 45:796-802.
75. Marelli A.J., Ionescu-Ittu R., Mackie A.S., Guo L., Dendukuri N., Kaouache M. Lifetime prevalence of congenital heart disease in the general population from 2000 to 2010. Circulation 2014, 130:749-756.
76. Roos-Hesselink J.W., Meijboom F.J., Spitaels S.E., vanDomburg R.T., vanRijen E.H., Utens E.M., et al. Long-term outcome after surgery for pulmonary stenosis (a longitudinal study of 22-33 years). Eur Heart J 2006, 27:482-488.
77. Edwards J.E., Christensen N.A., Clagett T., McDonald J.R. Pathological considerations in coarctation of the aorta. Proc Staff Meet Mayo Clin 1948, 23:324-332.
78. Ho S.Y., Anderson R.H. Coarctation, tubular hypoplasia and the ductus arteriosus. Br Heart J 1979, 41:268-274.
79. Glancy D.L., Morrow A.G., Simon Al, Roberts W.C. Juxtaductal aortic coarctation. Analysis of 84 patients studied hemodynamically, angiographically, and morphologically after age 1 year. Am J Cardiol 1983, 51:537-551.
80. Rudolph A.M., Heymann M.A., Spitznas U. Hemodynamic considerations in the development of narrowing of the aorta. Am J Cardiol 1972, 30:514-525.
81. Shinebourne E.A., Elseed A.M. Relation between fetal flow pattern, coarctation of the aorta, and pulmonary blood flow. Br Heart J 1974, 36:492-498.
82. Morales D.L.S., DiBardino D.J., Vick W., Fraser C.D., McKenzie E.D. Tetralogy of Fallot and hypoplastic aortic arch: a novel perspective. J Thorac Cardiovasc Surg 2005, 129:1448-1450.
83. Kotecha M.K., Krishnamanohar S.R., Kumar R.S. Absent pulmonary valve syndrome coexisting with coarctation of aorta in an adult. Congenit Heart Dis 2013, 8:E17-E19.
84. Towbin J.A., Belmont J. Molecular determinants of left and right outflow tract obstruction. Am J Med Genet 2000, 97:297-303.
85. Brown M.L., Burkhart H.M., Connolly H.M., Dearani J.A., Cetta F., Li Z., et al. Coarctation of the aorta: lifelong surveillance is mandatory following surgical repair. J Am Coll Cardiol 2013, 62:1020-1025.
86. Roberts W.C., Ko J.M. Some observations on mitral and aortic valve disease. Proc (Bayl Univ Med Cent) 2008, 21:282-299.
87. Roberts W.C., Vowels T.J., Ko J.M. Natural history of adults with congenitally malformed aortic valve (unicuspid or bicuspid). Medicine 2012, 91:287-308.
88. Hochstrasser L., Ruchat P., Sekarski N., Hurni M., von Segesser L.K. Long-term outcome of congenital aortic valve stenosis: predictors of reintervention. Cardiol Young 2015, 25(5):893-902.
89. Angelini P. Novel imaging of coronary artery anomalies to assess their prevalence, the causes of clinical symptoms, and the risk of sudden cardiac death. Circ Cardiovasc Imaging 2014, 7:747-754.
90. Choi J.H., Kornblum R.N. Peter Maravich's incredible heart. J Forensic Sci 1990, 35:981-986.
91. Kudumula V., Mehta C., Stumper O., Desai T., Chikermane A., Miller P., et al. Twenty-year outcome of anomalous origin of the left coronary artery from pulmonary artery: management of mitral regurgitation. Ann Thorac Surg 2014, 97:938-944.
92. Matturri L., Ottaviani G., Rossi L. Cardiac massage in infants. Intensive Care Med 2003, 29:1199-1200.
93. Husain S.A., Pasquali S.K., Jacobs J.P., Hill K.D., Kim S., Kane L.C., et al. Congenital heart operations performed in the first year of life: does geographic variation exist?. Ann Thorac Surg 2014, 98:912-918.
94. Edwards W.D. Postoperative pathology of congenital heart disease. Cardiovasc Pathol 2010, 19:275-280.
95. Rollins C.K., Watson C.G., Asaro L.A., Wypij D., Vajapeyam S., Bellinger D.C. White matter microstructure and cognition in adolescents with congenital heart disease. J Pediatr 2014, 165:936-944.
96. Yuan S.M., Jing H. Palliative procedures for congenital heart defects. Arch Cardiovasc Dis 2009, 102:549-557.
97. Frescura C., Thiene G. Cardiopatie congenite. Anatomia Patologica e Correlazioni Anatomo-cliniche 2007, vol. I:897-949. Piccin, Padova.
98. Frescura C., Thiene G. The new concept of univentricular heart. Front Pediatr 2014, 2(July):1-17. Article 62.
99. International Society for Heart and Lung Transplantation (ISHLT). Transplant registry quarterly reports for Heart in North America 2015. Available from: (accessed April 20, 2015). http://www.ishlt.org/registries/quarterlyDataReportResults.asp?organ=HR&rptType=all&continent=4.
100. Mullins C.E. Congenital heart disease in the adult: interventional therapy. Cardiovascular medicine 2007, 311-340. Springer-Verlag, London. 3rd ed. J.T. Willerson, J.N. Cohn, H.J.J. Wellens, D.R. Holmes (Eds.).
101. Yacoub M.H., Uebing A., Radley-Smith R., Gatzoulis M.A. Surgical treatment. Cardiovascular medicine 2007, 341-365. Springer-Verlag, London. 3rd ed. J.T. Willerson, J.N. Cohn, H.J.J. Wellens, D.R. Holmes (Eds.).
102. Everett A.D., Lim D.S. Illustrated field guide to congenital heart disease and repair 2010, Scientific Software Solutions, Charlottesville, VA. 3rd ed.
103. Lim D.S., Battle R.W., Everett A.D. Illustrated field guide to adult congenital disease 2009, Scientific Software Solutions, Charlottesville, VA.
104. Everett AD. Cove Po int Foundation Congenital Heart Disease. Helen B. Taussig Children's Heart Center, Johns Hopkins University. Available from: (accessed October 29, 2014). http://www.pted.org.
105. Gerlis L.M., Ho S.Y., Sommerville J. A postmortem review of congenital cardiac malformations in a series of 180 adults, over the age of 16 years, born between 1865 and 1980. Cardiovasc Pathol 1999, 8:263-272.
106. McManus B. Adult congenital heart disease-challenges and opportunities for pathologists. Cardiovasc Pathol 2010, 19:281-285.
107. Köhler D., Arnold R., Loukanov T., Gorenflo M. Right ventricular failure and pathobiology in patients with congenital heart disease-implications for long-term follow-up. Front Pediatr 2013, 1:37.
108. Greutmann M., Tobler D., Kovacs A.H., Greutmann-Yantiri M., Haile S.R., Held L., et al. Increasing mortality burden among adults with complex congenital heart disease. Congenit Heart Dis 2015, 10:117-127.
109. Wilson W., Osten M., Benson L., Horlick E. Evolving trends in interventional cardiology: endovascular options for congenital disease in adults. Can J Cardiol 2014, 30:75-86.
110. Bacha E., Kalfa D. Minimally invasive pediatric surgery. Nat Rev Cardiol 2014, 1:24-34.