Pediatric Partial and Intermediate Atrioventricular Septal Defects

No Results

No Results


Atrioventricular septal defects (AVSDs) refer to a broad spectrum of malformations characterized by a deficiency of the atrioventricular septum and abnormalities of the atrioventricular valves. These malformations are presumed to result from abnormal or inadequate fusion of the superior and inferior endocardial cushions with the mid portion of the atrial septum and the muscular (trabecular) portion of the ventricular septum.

Several methods of classification and nomenclature are recognized, causing considerable confusion. The term partial AVSD (also called partial common atrioventricular canal) generally refers to endocardial cushion defects, which have an interatrial communication but lack an interventricular communication. In these types of defects the mitral and tricuspid annuli are separate. In addition, certain anatomic features should be present, alone or in combination: primum atrial septal defect (ASD), inlet ventricular septal defect (VSD), cleft of the anterior mitral valve leaflet, and wide anteroseptal tricuspid valve commissure or cleft septal tricuspid leaflet (see the image below). The most frequently encountered abnormality in patients with partial AVSD is the combination of primum ASD and cleft of the anterior mitral valve leaflet.

The term intermediate AVSD (also called transitional common atrioventricular canal) is variably defined; however, it most commonly refers to the combination of a partial AVSD with a small interventricular communication. This is an infrequent form of AVSD. A single valvar annulus is usually present where the anterior and posterior bridging leaflets fuse overlying the ventricular septum. Because of the leaflets’ fusion, two distinct valvar components are observed (see the image below).

A thorough description of associated atrioventricular valve abnormalities should be included when classifying these defects.

This article considers AVSDs that demonstrate minimal or no shunting through an interventricular communication.

In the absence of obstruction of the right ventricular outflow tract, such as in pulmonary stenosis or pulmonary vascular obstructive disease, predominant left-to-right shunting occurs. The clinical presentation is determined by the degree of interatrial shunting, atrioventricular regurgitation, or both. The most inferior portion of the atrial septum is deficient. The resulting ostium primum defect varies in size and may occur in association with more superior ostium secundum–type ASDs. In some of the latter cases, only a small strand of the atrial septum remains, leading to the appearance of a common atrium. Some observers reserve the term common atrium for those cases with an additional sinus venosus deficiency.

The degree of left-to-right shunting through the atrial defect is determined by the size of the communication and the relative compliance of the 2 atria and ventricles. Ventricular compliance is affected by the level of pulmonary vascular resistance (PVR). In the newborn with a less compliant right ventricle (RV) and relatively high PVR, little left-to-right shunting occurs. If the defect is extremely large, obligatory mixing in a common, or near-common, atrium creates a component of right-to-left shunting. Left-to-right shunting increases with age as PVR decreases and RV compliance increases. This results in progressive RV enlargement and pulmonary vascular engorgement.

The atrioventricular valves are abnormal, even in a partial AVSD. Fusion failure of the endocardial cushions usually results in a separation or cleft in the anterior mitral valve leaflet. The degree of regurgitation through the cleft depends on its size and, occasionally, on the presence of left ventricular outflow tract (LVOT) obstruction or coarctation of the aorta. Typically, the cleft directs regurgitant blood through the atrial defect, creating an LV-to-RA (right atrium) shunt. RA enlargement, rather than left atrial (LA) enlargement, may occur. In addition, mitral regurgitation (MR) contributes to LA and LV enlargement.

AVSDs are presumed to occur secondary to extracellular matrix abnormalities that produce faulty development of the endocardial cushions and the atrioventricular septum. It has been recently described that yet another structure, the dorsal mesenchymal protrusion, which derives from the second heart field, should also fully develop in order to have an intact 4-chambered heart; otherwise, an ASD or an AVSD occurs. [1]

More detailed scientific theories interpret the normal development of the human heart as an orderly coordination of transcriptional programs. Therefore, the variety and range of anatomic malformations in CHD are believed to be caused by a faulty mechanism that disrupts the above.

AVSDs are often associated with genetic syndromes such as trisomy 21 or Down syndrome; Holt-Oram syndrome, which results from mutations in the TBX5 gene; and heterotaxy syndromes, which result from mutations in genes such as PITX2, SHH, and NODAL. A newly described CRELD1 gene is likely to be an AVSD-susceptibility gene, and CRELD1 mutations may increase the risk of developing a heart defect [2] ; this mutation is believed to be associated with the 3p deletion syndrome [3] characterized by low birth weight, varying degrees of mental retardation, ptosis, and micrognathia. [4]

Genetic mutations may be also associated with nonsyndromic cardiac defects. For example, one of the most important factors for the differentiation of mesodermal progenitor cells is the homeobox protein Nkx-2.5. In humans, 28 germline Nkx-2.5 mutations have been associated with CHD. Studies have shown that mutations in the gene Nkx-2.5 are associated specifically with AVSDs and VSDs. [5] Mutations in the GATA4 transcriptional factor may also cause AVSDs by disrupting its role during different stages in cardiogenesis. [6]

To date, approximately 100 CHD “risk genes” have been described. Of these, six subphenotypes have been shown to be linked to partial AVSDs. Of note, these genes have also been linked to aortic valve stenosis, subaortic stenosis, AVSDs associated with tetralogy of Fallot, tetralogy of Fallot, and truncus arteriosus. [7]

Prevalence estimates of cardiovascular malformations in large cohorts vary from 4-8 cases per 1000 births. AVSD constitutes 5-8% of these defects. Incidence of AVSD in fetuses is 17%; however, occurrence of partial AVSD has not been separated from this general classification.

Studies report the incidence of congenital heart defect (CHD) in children with Down syndrome (trisomy 21) to be 42-48%. Of those CHDs, 45% are AVSDs.

In general, when not associated with heterotaxia syndrome, AVSDs commonly occur in Down syndrome.

Partial AVSD, as opposed to complete AVSD, of the ostium primum type is more common in patients without Down syndrome.

International frequency of cardiovascular malformations is similar to US figures.

Left-to-right shunting through the atrial communication is generally well tolerated through the first decade of life. Patients are asymptomatic if MR is mild or absent. Symptoms of left-to-right shunting may develop in adolescence and are exacerbated by atrial arrhythmia. Sinus node dysfunction may occur and contributes to exercise intolerance if the defect is not repaired.

Moderate to severe MR may lead to morbidity in infancy and early childhood. Severe MR causes congestive heart failure (CHF) and failure to thrive in infants; it may result in death if left untreated.

A large left-to-right shunt from the LV to the RA through a cleft mitral valve causes volume overload in both ventricles, with CHF early in life.

Miller et al reviewed the long-term survival of infants with all types of atrioventricular septal defects with Down syndrome (n = 177) and without Down syndrome (n = 161). In this cohort, born from 1979-2003, overall survival probability through 2004 was 70% in those with Down syndrome and 69% in those without. Mortality was higher in children with a complex atrioventricular septal defect and in those with 2 or more major noncardiac malformations, but was lower in children born in 1992-2003. [8]

Briggs LE, 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 Jul. 84(1):117-30. [Medline]. [Full Text].

Guo Y, Shen J, Yuan L, Li F, Wang J, Sun K. Novel CRELD1 gene mutations in patients with atrioventricular septal defect. World J Pediatr. 2010 Nov. 6(4):348-52. [Medline].

Robinson SW, Morris CD, Goldmuntz E, et al. Missense mutations in CRELD1 are associated with cardiac atrioventricular septal defects. Am J Hum Genet. 2003 Apr. 72(4):1047-52. [Medline]. [Full Text].

Green EK, Priestley MD, Waters J, Maliszewska C, Latif F, Maher ER. Detailed mapping of a congenital heart disease gene in chromosome 3p25. J Med Genet. 2000 Aug. 37(8):581-7. [Medline]. [Full Text].

Inga A, Reamon-Buettner SM, Borlak J, Resnick MA. Functional dissection of sequence-specific NKX2-5 DNA binding domain mutations associated with human heart septation defects using a yeast-based system. Hum Mol Genet. 2005 Jul 15. 14(14):1965-75. [Medline].

Moskowitz IP, Wang J, Peterson MA, et al. Transcription factor genes Smad4 and Gata4 cooperatively regulate cardiac valve development. [corrected]. Proc Natl Acad Sci U S A. 2011 Mar 8. 108(10):4006-11. [Medline]. [Full Text].

Tomita-Mitchell A, Mahnke DK, Struble CA, et al. Human gene copy number spectra analysis in congenital heart malformations. Physiol Genomics. 2012 May 1. 44(9):518-41. [Medline]. [Full Text].

Miller A, Siffel C, Lu C, Riehle-Colarusso T, Frias JL, Correa A. Long-term survival of infants with atrioventricular septal defects. J Pediatr. 2010 Jun. 156(6):994-1000. [Medline].

Kutty S, Smallhorn JF. Evaluation of atrioventricular septal defects by three-dimensional echocardiography: benefits of navigating the third dimension. J Am Soc Echocardiogr. 2012 Sep. 25(9):932-44. [Medline].

Cheng HL, Huang CH, Tsai HE, Chen MY, Fan SZ, Hsiao PN. Intraoperative assessment of partial atrioventricular septal defect with a cleft mitral valve by real-time three-dimensional transesophageal echocardiography. Anesth Analg. 2012 Apr. 114(4):731-4. [Medline].

Mitchell FM, Prasad SK, Greil GF, Drivas P, Vassiliou VS, Raphael CE. Cardiovascular magnetic resonance: diagnostic utility and specific considerations in the pediatric population. World J Clin Pediatr. 2016 Feb 8. 5(1):1-15. [Medline]. [Full Text].

Ashfaq A, Brown T, Reemtsen B. Repair of complete atrioventricular septal defects with decellularized extracellular matrix: initial and midterm outcomes. World J Pediatr Congenit Heart Surg. 2017 May. 8(3):310-4. [Medline]. [Full Text].

Prifti E, Bonacchi M, Bernabei M, et al. Repair of complete atrioventricular septal defects in patients weighing less than 5 kg. Ann Thorac Surg. 2004 May. 77(5):1717-26. [Medline].

Jacobs JP, O’Brien SM, Pasquali SK, et al. Variation in outcomes for benchmark operations: an analysis of the Society of Thoracic Surgeons Congenital Heart Surgery Database. Ann Thorac Surg. 2011 Dec. 92(6):2184-91; discussion 2191-2. [Medline]. [Full Text].

Kaza AK, Colan SD, Jaggers J, et al. Surgical interventions for atrioventricular septal defect subtypes: the pediatric heart network experience. Ann Thorac Surg. 2011 Oct. 92(4):1468-75; discussion 1475. [Medline]. [Full Text].

Minich LL, Atz AM, Colan SD, et al. Partial and transitional atrioventricular septal defect outcomes. Ann Thorac Surg. 2010 Feb. 89(2):530-6. [Medline]. [Full Text].

Devlin PJ, Backer CL, Eltayeb O, Monge MC, Hauck AL, Costello JM. Repair of partial atrioventricular septal defect: age and outcomes. Ann Thorac Surg. 2016 Jul. 102(1):170-7. [Medline]. [Full Text].

Krupickova S, Morgan GJ, Cheang MH, et al. Symptomatic partial and transitional atrioventricular septal defect repaired in infancy. Heart. 2018 Sep. 104(17):1411-6. [Medline].

Konstantinov IE, Buratto E. Repair of partial atrioventricular septal defects in infancy: a paradigm shift or a road block?. Heart. 2018 Sep. 104(17):1388-9. [Medline]. [Full Text].

Poirier NC, Williams WG, Van Arsdell GS, et al. A novel repair for patients with atrioventricular septal defect requiring reoperation for left atrioventricular valve regurgitation. Eur J Cardiothorac Surg. 2000 Jul. 18(1):54-61. [Medline].

Sughimoto K, d’Udekem Y, Konstantinov IE, Brizard CP. Mid-term outcome with pericardial patch augmentation for redo left atrioventricular valve repair in atrioventricular septal defect†. Eur J Cardiothorac Surg. 2016 Jan. 49(1):157-66. [Medline]. [Full Text].

Ten Harkel AD, Cromme-Dijkhuis AH, Heinerman BC, et al. Development of left atrioventricular valve regurgitation after correction of atrioventricular septal defect. Ann Thorac Surg. 2005 Feb. 79(2):607-12. [Medline].

Murashita T, Kubota T, Oba J, Aoki T, Matano J, Yasuda K. Left atrioventricular valve regurgitation after repair of incomplete atrioventricular septal defect. Ann Thorac Surg. 2004 Jun. 77(6):2157-62. [Medline].

Aeba R, Kudo M, Okamoto K, Yozu R. Bridging annuloplasty for left atrioventricular valve of partial atrioventricular septal defect. Ann Thorac Surg. 2012 May. 93(5):e137-9. [Medline].

Manning PB. Partial atrioventricular canal: pitfalls in technique. Semin Thorac Cardiovasc Surg Pediatr Card Surg Annu. 2007. 42-6. [Medline].

Stulak JM, Burkhart HM, Dearani JA, et al. Reoperations after repair of partial atrioventricular septal defect: a 45-year single-center experience. Ann Thorac Surg. 2010 May. 89(5):1352-9. [Medline].

Abbruzzese PA, Napoleone A, Bini RM. Late left atrioventricular valve insufficiency after repair of partial atrioventricular septal defects: anatomical and surgical determinants. Ann Thorac Surg. 1990 Jan. 49(1):111-4. [Medline].

Aubert S, Henaine R, Raisky O, et al. Atypical forms of isolated partial atrioventricular septal defect increase the risk of initial valve replacement and reoperation. Eur J Cardiothorac Surg. 2005 Aug. 28(2):223-8. [Medline].

Najm HK, Williams WG, Chuaratanaphong S, Watzka SB, Coles JG, Freedom RM. Primum atrial septal defect in children: early results, risk factors, and freedom from reoperation. Ann Thorac Surg. 1998 Sep. 66(3):829-35. [Medline].

Jacobs JP, Jacobs ML, Mavroudis C, et al. Atrioventricular septal defects: lessons learned about patterns of practice and outcomes from the congenital heart surgery database of the society of thoracic surgeons. World J Pediatr Congenit Heart Surg. 2010 Apr. 1(1):68-77. [Medline].

Cooper WO, Hernandez-Diaz S, Arbogast PG, et al. Major congenital malformations after first-trimester exposure to ACE inhibitors. N Engl J Med. 2006 Jun 8. 354(23):2443-51. [Medline].

Allwork SP. Anatomical-embryological correlates in atrioventricular septal defect. Br Heart J. 1982 May. 47(5):419-29. [Medline].

Ebels T, Ho SY, Anderson RH, Meijboom EJ, Eijgelaar A. The surgical anatomy of the left ventricular outflow tract in atrioventricular septal defect. Ann Thorac Surg. 1986 May. 41(5):483-8. [Medline].

Ferencz C, Rubin JD, Loffredo CA, eds. The Epidemiology of Congenital Heart Disease, The Baltimore-Washington Infant Heart Study (1981-1989). Perspectives in Pediatric Cardiology. Mount Kisco, NY: Futura Publishing Co; 1993. Vol 4:

Freeman SB, Taft LF, Dooley KJ, et al. Population-based study of congenital heart defects in Down syndrome. Am J Med Genet. 1998 Nov 16. 80(3):213-7. [Medline].

Jacobstein MD, Fletcher BD, Goldstein S, Riemenschneider TA. Evaluation of atrioventricular septal defect by magnetic resonance imaging. Am J Cardiol. 1985 Apr 15. 55(9):1158-61. [Medline].

LaCorte MA, Cooper RS, Kauffman SL, et al. Atrioventricular canal ventricular septal defect with cleft mitral valve. Angiographic and echocardiographic features. Pediatr Cardiol. 1982. 2(4):289-95. [Medline].

Lipshultz SE, Sanders SP, Mayer JE, Colan SD, Lock JE. Are routine preoperative cardiac catheterization and angiography necessary before repair of ostium primum atrial septal defect?. J Am Coll Cardiol. 1988 Feb. 11(2):373-8. [Medline].

Neufeld HN, Titus JL, Dushane JW, BUrchell HB, Edwards JE. Isolated ventricular septal defect of the persistent common atrioventricular canal type. Circulation. 1961 May. 23:685-96. [Medline].

Parsons JM, Baker EJ, Anderson RH, et al. Morphological evaluation of atrioventricular septal defects by magnetic resonance imaging. Br Heart J. 1990 Aug. 64(2):138-45. [Medline].

Piccoli GP, Gerlis LM, Wilkinson JL, et al. Morphology and classification of atrioventricular defects. Br Heart J. 1979 Dec. 42(6):621-32. [Medline].

Portman MA, Beder SD, Ankeney JL. A 20-year review of ostium primum defect repair in children. Am Heart J. 1985 Nov. 110(5):1054-8. [Medline].

Portman MA, Beder SD, Cohen MH, et al. Conduction abnormalities detected by electrophysiologic testing following repair of ostium primum atrioventricular septal defect. Int J Cardiol. 1986 Apr. 11(1):111-9. [Medline].

Pretre R, Dave H, Kadner A. Direct closure of the septum primum in atrioventricular canal defects. J Thorac Cardiovasc Surg. 2004 Jun. 127(6):1678-81.

Sadeghi AM, Laks H, Pearl JM. Primum atrial septal defect. Semin Thorac Cardiovasc Surg. 1997 Jan. 9(1):2-7. [Medline].

Singh A, Romp RL, Nanda NC, et al. Usefulness of live/real time three-dimensional transthoracic echocardiography in the assessment of atrioventricular septal defects. Echocardiography. 2006 Aug. 23(7):598-608. [Medline].

van den Bosch AE, van Dijk VF, McGhie JS, et al. Real-time transthoracic three-dimensional echocardiography provides additional information of left-sided AV valve morphology after AVSD repair. Int J Cardiol. 2006 Jan 26. 106(3):360-4. [Medline].

Wang ZJ, Reddy GP, Gotway MB, et al. Cardiovascular shunts: MR imaging evaluation. Radiographics. 2003 Oct. 23 Spec No:S181-94. [Medline].

M Silvana Horenstein, MD Assistant Professor, Department of Pediatrics, University of Texas Medical School at Houston; Medical Doctor Consultant, Legacy Department, Best Doctors, Inc

M Silvana Horenstein, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Cardiology, American Medical Association

Disclosure: Nothing to disclose.

Michael A Portman, MD, MD Professor, Department of Pediatrics, University of Washington School of Medicine; Director of Research, Division of Cardiology, Seattle Children’s Hospital; Attending Physician, Seattle Children’s Heart Center; Attending Physician, Cardiology Clinic, Providence Everett Medical Center

Michael A Portman, MD, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Cardiology, American Heart Association, American Physiological Society, Society for Pediatric Research

Disclosure: Nothing to disclose.

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Alvin J Chin, MD Emeritus Professor of Pediatrics, University of Pennsylvania School of Medicine

Disclosure: Nothing to disclose.

Syamasundar Rao Patnana, MD Professor of Pediatrics and Medicine, Division of Cardiology, Emeritus Chief of Pediatric Cardiology, University of Texas Medical School at Houston and Children’s Memorial Hermann Hospital

Syamasundar Rao Patnana, MD is a member of the following medical societies: American Academy of Pediatrics, American Pediatric Society, American College of Cardiology, American Heart Association, Society for Cardiovascular Angiography and Interventions, Society for Pediatric Research

Disclosure: Nothing to disclose.

Paul M Seib, MD Associate Professor of Pediatrics, University of Arkansas for Medical Sciences; Medical Director, Cardiac Catheterization Laboratory, Co-Medical Director, Cardiovascular Intensive Care Unit, Arkansas Children’s Hospital

Paul M Seib, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Cardiology, American Heart Association, Arkansas Medical Society, International Society for Heart and Lung Transplantation, Society for Cardiovascular Angiography and Interventions

Disclosure: Nothing to disclose.

Pediatric Partial and Intermediate Atrioventricular Septal Defects

Research & References of Pediatric Partial and Intermediate Atrioventricular Septal Defects|A&C Accounting And Tax Services