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Isolated left ventricular non-compaction: the case for abnormal myocardial development

Published online by Cambridge University Press:  26 February 2007

Ross A. Breckenridge ,
Robert H. Anderson  and
Perry M. Elliott
Ross A. Breckenridge
Affiliation:
Department of Clinical Pharmacology, BHF Laboratories, University College, London
Robert H. Anderson
Affiliation:
Cardiac Unit, Institute of Child Heath, University College, London
Perry M. Elliott
Affiliation:
The Heart Hospital, University College, London
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Abstract

Isolated ventricular non-compaction is an increasingly commonly diagnosed myocardial disorder characterised by excessive and prominent trabeculation of the morphologically left, and occasionally the right, ventricle. This is associated with high rates of thromboembolism, cardiac failure, and cardiac arrhythmia. Recent improvements in understanding the embryonic processes underlying ventricular formation have led to the hypothesis that ventricular non-compaction is due to a failure of normal ventriculogenesis, leading to abnormal myocardium which may present clinically many years later. Experimental work in animal models provides several candidate transcription factors and signalling molecules that could, in theory, cause ventricular non-compaction if disrupted.

Keywords

hypertrabeculationmolecular biologytranscription factors
Type
Review Article
Information
Cardiology in the Young , Volume 17 , Issue 2 , April 2007 , pp. 124 - 129
Copyright
© 2007 Cambridge University Press

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References

Freedom RM, Yoo S-J, Perrin D, Petersen S, Anderson RH. The morphological spectrum of ventricular noncompaction. Cardiol Young 2005; 15: 345–364.Google Scholar
Weiford BC, Subbarao VD, Mulhern KM. Noncompaction of the ventricular myocardium. Circulation 2004; 109: 2965–2971.Google Scholar
Sasse-Klaassen S, Gerull B, Oechslin E, Jenni R, Thierfelder L. Isolated noncompaction of the left ventricular myocardium in the adult is an autosomal dominant disorder in the majority of patients. Am J Med Genet 2003; 119A: 162–167.Google Scholar
Sasse-Klaassen S, Probst S, Gerull B, et al. Novel gene locus for autosomal dominant left ventricular noncompaction maps to chromosome 11p15. Circulation 2004; 109: 2720–2723.Google Scholar
Stollberger C, Finsterer J, Blazek G. Left ventricular hypertrabeculation/noncompaction and association with additional cardiac abnormalities and neuromuscular disorders. Am J Cardiol 2002; 90: 899–902.Google Scholar
Oechslin EN, Attenhofer Jost CH, Rojas JR, Kaufmann PA, Jenni R. Long-term follow-up of 34 adults with isolated left ventricular noncompaction: a distinct cardiomyopathy with poor prognosis. J Am Coll Cardiol 2000; 36: 493–500.Google Scholar
Ichida F, Hamamichi Y, Miyawaki T, et al. Clinical features of isolated noncompaction of the ventricular myocardium: long-term clinical course, hemodynamic properties, and genetic background. J Am Coll Cardiol 1999; 34: 233–240.Google Scholar
Rigopoulos A, Rizos IK, Aggeli C, et al. Isolated left ventricular noncompaction: an unclassified cardiomyopathy with severe prognosis in adults. Cardiology 2002; 98: 25–32.Google Scholar
Pignatelli RH, McMahon CJ, Dreyer WJ, et al. Clinical characterization of left ventricular noncompaction in children: a relatively common form of cardiomyopathy. Circulation 2003; 108: 2672–2678.Google Scholar
Murphy RT, Thaman R, Blanes JG, et al. Natural history and familial characteristics of isolated left ventricular non-compaction. Eur Heart J 2005; 26: 187–192.Google Scholar
Chin TK, Perloff JK, Williams RG, Jue K, Mohrmann R. Isolated noncompaction of the ventricular myocardium. A study of eight cases. Circulation 1990; 82: 507–513.Google Scholar
Jenni R, Oechslin E, Schneider J, Jost CA, Kaufmann PA. Echocardiographic and pathoanatomical characteristics of isolated left ventricular non-compaction: a step towards classification as a distinct cardiomyopathy. Heart 2001; 86: 666–671.Google Scholar
Petersen SE, Selvanayagam JB, Wiesmann F, et al. Left ventricular non-compaction: insights from cardiovascular magnetic resonance imaging. J Am Coll Cardiol 2005; 46: 101–105.Google Scholar
Stollberger C, Finsterer J, Kopsa W. Magnetic resonance imaging does not always confirm left ventricular noncompaction. Int J Cardiol 2007; 114: E48–9.Google Scholar
Moorman AF, Lamers WH. Development of the conduction system of the vertebrate heart. In: Harvey RP, Rosenthal N (eds). Heart Development. Academic Press, San Diego, 1999, pp. 195–207.
Sedmera D, Pexieder T, Vuillemin M, Thompson RP, Anderson RH. Developmental Patterning of the Myocardium. Anat Rec 2000; 258: 319–337.Google Scholar
Sedmera D, Thomas PS. Trabeculation in the human heart. Bioessays 1996; 18: 607.Google Scholar
Miquerol L, Dupays L, Thevenau-Ruissy M, et al. Gap junctional connexins in the developing mouse cardiac conduction system. Novartis Foundation Symposia 2003; 250: 80–98.Google Scholar
Junga G, Kneifel S, Von Smekal A, Steinert H, Bauersfeld U. Myocardial ischaemia in children with isolated ventricular non-compaction. Eur Heart J 1999; 20: 910–916.Google Scholar
Jenni R, Wyss CA, Oechslin EN, Kaufmann PA. Isolated ventricular noncompaction is associated with coronary microcirculatory dysfunction. J Am Coll Cardiol 2002; 39: 450–454.Google Scholar
Mikawa T, Borisov A, Brown AM, Fischman DA. Clonal analysis of cardiac morphogenesis in the chicken embryo using a replication-defective retrovirus: I. Formation of the ventricular myocardium. Dev Dyn 1992; 193: 11–23.Google Scholar
Chen J, Kubalak SW, Chien KR. Ventricular muscle-restricted targeting of the RXRalpha gene reveals a non-cell-autonomous requirement in cardiac chamber morphogenesis. Development 1998; 125: 1943–1949.Google Scholar
Stuckmann I, Evans S, Lassar AB. Erythropoietin and retinoic acid, secreted from the epicardium, are required for cardiac myocyte proliferation. Dev Biol 2003; 255: 334–349.Google Scholar
Lavine KJ, Yu K, White AC, et al. Endocardial and epicardial derived FGF signals regulate myocardial proliferation and differentiation in vivo. Dev Cell 2005; 8: 85–95.Google Scholar
Sucov HM, Dyson E, Gummeringer CL, Price J, Chien KR, Evans RM. RXR alpha mutant mice establish agenetic basis for vitamin A signalling in heart morphogenesis. Genes Dev 1994; 8: 1007–1008.Google Scholar
Bruneau BG. The developing heart and congenital heart defects: a make or break situation. Clin Genet 2003; 63: 252–261.Google Scholar
Brand T. Heart development: molecular insights into cardiac specification and early morphogenesis. Dev Biol 2003; 258: 1–19.Google Scholar
Harvey RP, Lai D, Elliott D, et al. Homeodomain factor Nkx2-5 in heart development and disease. Cold Spring Harb Symp Quant Biol 2002; 67: 107–114.Google Scholar
Olson EN, Schneider MD. Sizing up the heart: development redux in disease. Genes Dev 2003; 17: 1937–1956.Google Scholar
Olson EN. A decade of discoveries in cardiac biology. Nat Med 2004; 10: 467–474.Google Scholar
Lints TJ, Parsons LM, Hartley L, Lyons I, Harvey RP. Nkx-2.5: a novel murine homeobox gene expressed in early heart progenitor cells and their myogenic descendants. Development 1993; 119: 969.Google Scholar
Komuro I, Izumo S. Csx: a murine homeobox-containing gene specifically expressed in the developing heart. Proc Natl Acad Sci U S A 1993; 90: 8145–8149.Google Scholar
Bruneau BG, Nemer G, Schmitt JP, et al. A murine model of Holt-Oram syndrome defines roles of the T-box transcription factor Tbx5 in cardiogenesis and disease. Cell 2001; 106: 709–721.Google Scholar
Takeuchi JK, Mileikovskaia M, Koshiba-Takeuchi K, et al. Tbx20 dose-dependently regulates transcription factor networks required for mouse heart and motoneuron development. Development 2005; 132: 2463–2474.Google Scholar
Durocher D, Nemer M. Combinatorial interactions regulating cardiac transcription. Dev Genet 1998; 22: 250–262.Google Scholar
Kasahara H, Benson DW. Biochemical analysis of eight NKX2.5 homeodomain missense mutations causing atrioventricular block and cardiac anomalies. Cardiovasc Res 2004; 64: 40–51.Google Scholar
Schott JJ, Benson DW, Basson CT, et al. Congenital heart disease caused by mutations in the transcription factor NKX2-5. Science 1998; 281: 108–111.Google Scholar
Biben C, Harvey RP. Homeodomain factor Nkx2.5 controls left-right expression of bHLH gene eHAND during murine heart development. Genes Dev 1997; 11: 1357–1369.Google Scholar
Lyons I, Parsons LM, Hartley L, et al. Myogenic and morphogenic defects in heart tubes of murine embryos lacking the homeobox gene Nkx2-5. Genes Dev 1995; 9: 1654–1666.Google Scholar
Pashmforoush M, Lu JT, Chen H, et al. Nkx2-5 pathways and congenital heart disease; loss of ventricular myocyte lineage specification leads to progressive cardiomyopathy and complete heart block. Cell 2004; 117: 373–86.Google Scholar
Neuhaus H, Rosen V, Thies RS. Heart specific expression of mouse BMP-10 a novel member of the TGF-beta superfamily. Mech Dev 1999; 80: 181–184.Google Scholar
Chen H, Shi S, Acosta L, et al. BMP10 is essential for maintaining cardiac growth during murine cardiogenesis. Development 2004; 131: 2219–2231.Google Scholar
Gaussin V, Van de Putte T, Mishina Y, et al. Endocardial cushion and myocardial defects after cardiac myocyte-specific conditional deletion of the bone morphogenetic protein receptor ALK3. Proc Natl Acad Sci U S A 2002; 99: 2878–2883.Google Scholar
Sato Y, Ferguson DG, Sako H, et al. Cardiac-specific overexpression of mouse cardiac calsequestrin is associated with depressed cardiovascular function and hypertrophy in transgenic mice. J Biol Chem 1998; 273: 28470–28477.Google Scholar
Xin HB, Senbonmatsu T, Cheng DS, et al. Oestrogen protects FKBP12.6 null mice from cardiac hypertrophy. Nature 2002; 416: 334–338.Google Scholar
Kenton AB, Sanchez X, Coveler KJ, et al. Isolated left ventricular noncompaction is rarely caused by mutations in G4.5, alpha- dystrobrevin and FK Binding Protein-12. Mol Genet Metab 2004; 82: 162–166.Google Scholar
Bruneau BG, Logan M, Davis N, et al. Chamber-specific cardiac expression of Tbx5 and heart defects in Holt-Oram syndrome. Dev Biol 1999; 211: 100–108.Google Scholar
Digilio MC, Marino B, Bevilacqua M, Musolino AM, Giannotti A, Dallapiccola B. Genetic heterogeneity of isolated noncompaction of the left ventricular myocardium. Am J Med Genet 1999; 85: 90–91.Google Scholar
Bione S, D'Adamo P, Maestrini E, Gedeon AK, Bolhuis PA, Toniolo D. A novel X-linked gene, G4.5. is responsible for Barth syndrome. Nat Genet 1996; 12: 385–389.Google Scholar
Bleyl SB, Mumford BR, Brown-Harrison MC, et al. Xq28-linked noncompaction of the left ventricular myocardium: prenatal diagnosis and pathologic analysis of affected individuals. Am J Med Genet 1997; 72: 257–265.Google Scholar
Bleyl SB, Mumford BR, Thompson V, et al. Neonatal, lethal noncompaction of the left ventricular myocardium is allelic with Barth syndrome. Am J Hum Genet 1997; 61: 868–872.Google Scholar
Chen R, Tsuji T, Ichida F, et al. Mutation analysis of the G4.5 gene in patients with isolated left ventricular noncompaction. Mol Genet Metab 2002; 77: 319–325.Google Scholar
Pauli RM, Scheib-Wixted S, Cripe L, Izumo S, Sekhon GS. Ventricular noncompaction and distal chromosome 5q deletion. Am J Med Genet 1999; 85: 419–423.Google Scholar
Vatta M, Mohapatra B, Jimenez S, et al. Mutations in Cypher/ZASP in patients with dilated cardiomyopathy and left ventricular non-compaction. J Am Coll Cardiol 2003; 42: 2014–2027.Google Scholar
Hermida-Prieto M, Monserrat L, Castro-Beiras A, et al. Familial dilated cardiomyopathy and isolated left ventricular noncompaction associated with lamin A/C gene mutations. Am J Cardiol 2004; 94: 50–54.Google Scholar
Guntheroth W, Komarniski C, Atkinson W, Flinger CL. Criterion for fetal spongiform cardiomyopathy:restrictive pathophysiology. Obstet Gyneacol 2002; 99: 882–885.Google Scholar