OMIA 000654-9615 : Mitral valve disease in Canis lupus familiaris

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 157700 , 607829 , 610840

Mendelian trait/disorder: no

Mode of inheritance: Multifactorial

Considered a defect: yes

Key variant known: no

Species-specific name: Myxomatous mitral valve disease

Species-specific symbol: MMVD

Mapping: By conducting a GWAS on 139 affected and 102 normal Cavalier King Charles Spaniels, each genotyped with the Canine HD Bead Chip (yielding 84,693 SNPs for analysis), Madsen et al. (2011) "identified a 1.58 Mb region on CFA13 (P(genome) = 4.0× 10(-5)) and a 1.68 Mb region on CFA14 (P(genome) = 7.9× 10(-4)) associated with development of MMVD".

By conducting a GWAS on 36 Cavalier King Charles Spaniel, each genotyped with the Illumina HD SNP chip (yielding more than 170,000 SNPs for analysis), French et al. (2012) were not able to identify any chromosomal regions of interest.

Breed: Cavalier King Charles Spaniel.


Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
2020 Brambilla, P.G., Polli, M., Pradelli, D., Papa, M., Rizzi, R., Bagardi, M., Bussadori, C. :
Epidemiological study of congenital heart diseases in dogs: Prevalence, popularity, and volatility throughout twenty years of clinical practice. PLoS One 15:e0230160, 2020. Pubmed reference: 32716943. DOI: 10.1371/journal.pone.0230160.
Oyama, M.A., Elliott, C., Loughran, K.A., Kossar, A.P., Castillero, E., Levy, R.J., Ferrari, G. :
Comparative pathology of human and canine myxomatous mitral valve degeneration: 5HT and TGF-β mechanisms. Cardiovasc Pathol 46:107196, 2020. Pubmed reference: 32006823. DOI: 10.1016/j.carpath.2019.107196.
2019 Christiansen, L.B., Cremer, S.E., Helander, A., Madsen, T., Reimann, M.J., Møller, J.E., Höglund, K., Ljungvall, I., Häggström, J., Olsen, L.H. :
Urine 5-hydroxyindoleacetic acid in Cavalier King Charles spaniels with preclinical myxomatous mitral valve disease. Vet J 250:36-43, 2019. Pubmed reference: 31383418. DOI: 10.1016/j.tvjl.2019.06.005.
Li, Q., Heaney, A., Langenfeld-McCoy, N., Boler, B.V., Laflamme, D.P. :
Dietary intervention reduces left atrial enlargement in dogs with early preclinical myxomatous mitral valve disease: a blinded randomized controlled study in 36 dogs. BMC Vet Res 15:425, 2019. Pubmed reference: 31775756. DOI: 10.1186/s12917-019-2169-1.
2018 Carvalho, E.R., Ampuero, R.A.N., Tuleski, G.L.R., Camacho, A.A., Sousa, M.G. :
Polymorphism, coupling interval and prematurity index in dogs with degenerative mitral valve disease and ventricular arrhythmias. Vet Res Commun :, 2018. Pubmed reference: 29536334. DOI: 10.1007/s11259-018-9718-0.
2017 Belanger, J.M., Bellumori, T.P., Bannasch, D.L., Famula, T.R., Oberbauer, A.M. :
Correlation of neuter status and expression of heritable disorders. Canine Genet Epidemiol 4:6, 2017. Pubmed reference: 28560045. DOI: 10.1186/s40575-017-0044-6.
2016 Ahn, S.T., Suh, S.I., Moon, H., Hyun, C. :
Evaluation of growth differentiation factor 11 (GDF11) levels in dogs with chronic mitral valve insufficiency. Can J Vet Res 80:90-2, 2016. Pubmed reference: 26733738.
Apple, S.M., Menciotti, G., Braz-Ruivo, L., Crosara, S., Häggström, J., Borgarelli, M. :
Effects of pimobendan on myocardial perfusion and pulmonary transit time in dogs with myxomatous mitral valve disease: a pilot study. Aust Vet J 94:324-8, 2016. Pubmed reference: 27569835. DOI: 10.1111/avj.12480.
Boswood, A., Häggström, J., Gordon, S.G., Wess, G., Stepien, R.L., Oyama, M.A., Keene, B.W., Bonagura, J., MacDonald, K.A., Patteson, M., Smith, S., Fox, P.R., Sanderson, K., Woolley, R., Szatmári, V., Menaut, P., Church, W.M., O'Sullivan, M.L., Jaudon, J.P., Kresken, J.G., Rush, J., Barrett, K.A., Rosenthal, S.L., Saunders, A.B., Ljungvall, I., Deinert, M., Bomassi, E., Estrada, A.H., Fernandez Del Palacio, M.J., Moise, N.S., Abbott, J.A., Fujii, Y., Spier, A., Luethy, M.W., Santilli, R.A., Uechi, M., Tidholm, A., Watson, P. :
Effect of Pimobendan in Dogs with Preclinical Myxomatous Mitral Valve Disease and Cardiomegaly: The EPIC Study-A Randomized Clinical Trial. J Vet Intern Med :, 2016. Pubmed reference: 27678080. DOI: 10.1111/jvim.14586.
Höllmer, M., Willesen, J.L., Tolver, A., Koch, J. :
Left atrial volume and function in dogs with naturally occurring myxomatous mitral valve disease. J Vet Cardiol :, 2016. Pubmed reference: 27825670. DOI: 10.1016/j.jvc.2016.08.006.
Janus, I., Noszczyk-Nowak, A., Nowak, M., Ciaputa, R., Kandefer-Gola, M., Pasławska, U. :
A comparison of the histopathologic pattern of the left atrium in canine dilated cardiomyopathy and chronic mitral valve disease. BMC Vet Res 12:3, 2016. Pubmed reference: 26728624. DOI: 10.1186/s12917-015-0626-z.
Kim, H.S., Kang, J.H., Jeung, E.B., Yang, M.P. :
Serum Concentrations of Leptin and Adiponectin in Dogs with Myxomatous Mitral Valve Disease. J Vet Intern Med 30:1589-1600, 2016. Pubmed reference: 27573621. DOI: 10.1111/jvim.14570.
Martinelli, E., Locatelli, C., Bassis, S., Crosara, S., Paltrinieri, S., Scarpa, P., Spalla, I., Zanaboni, A.M., Quintavalla, C., Brambilla, P. :
Preliminary Investigation of Cardiovascular-Renal Disorders in Dogs with Chronic Mitral Valve Disease. J Vet Intern Med 30:1612-1618, 2016. Pubmed reference: 27717188. DOI: 10.1111/jvim.14524.
Mavropoulou, A., Guazzetti, S., Borghetti, P., De Angelis, E., Quintavalla, C. :
Cytokine expression in peripheral blood mononuclear cells of dogs with mitral valve disease. Vet J :, 2016. Pubmed reference: 27033593. DOI: 10.1016/j.tvjl.2016.03.002.
Nakamura, K., Morita, T., Osuga, T., Morishita, K., Sasaki, N., Ohta, H., Takiguchi, M. :
Prognostic Value of Right Ventricular Tei Index in Dogs with Myxomatous Mitral Valvular Heart Disease. J Vet Intern Med 30:69-75, 2016. Pubmed reference: 26789419. DOI: 10.1111/jvim.13820.
Sakarin, S., Rungsipipat, A., Surachetpong, S.D. :
Galectin-3 in cardiac muscle and circulation of dogs with degenerative mitral valve disease. J Vet Cardiol 18:34-46, 2016. Pubmed reference: 26786977. DOI: 10.1016/j.jvc.2015.10.007.
Yu, I.B., Huang, H.P. :
Prevalence and Prognosis of Anemia in Dogs with Degenerative Mitral Valve Disease. Biomed Res Int 2016:4727054, 2016. Pubmed reference: 27840827. DOI: 10.1155/2016/4727054.
2015 Birkegård, A.C., Reimann, M.J., Martinussen, T., Häggström, J., Pedersen, H.D., Olsen, L.H. :
Breeding Restrictions Decrease the Prevalence of Myxomatous Mitral Valve Disease in Cavalier King Charles Spaniels over an 8- to 10-Year Period. J Vet Intern Med 30:63-8, 2015. Pubmed reference: 26578464. DOI: 10.1111/jvim.13663.
Borgarelli, M., Abbott, J., Braz-Ruivo, L., Chiavegato, D., Crosara, S., Lamb, K., Ljungvall, I., Poggi, M., Santilli, R.A., Haggstrom, J. :
Prevalence and prognostic importance of pulmonary hypertension in dogs with myxomatous mitral valve disease. J Vet Intern Med 29:569-74, 2015. Pubmed reference: 25818210. DOI: 10.1111/jvim.12564.
Jung, S.W., Sun, W., Griffiths, L.G., Kittleson, M.D. :
Atrial Fibrillation as a Prognostic Indicator in Medium to Large-Sized Dogs with Myxomatous Mitral Valvular Degeneration and Congestive Heart Failure. J Vet Intern Med 30:51-7, 2015. Pubmed reference: 26681398. DOI: 10.1111/jvim.13800.
Lu, C.C., Liu, M.M., Clinton, M., Culshaw, G., Argyle, D.J., Corcoran, B.M. :
Developmental pathways and endothelial to mesenchymal transition in canine myxomatous mitral valve disease. Vet J 206:377-84, 2015. Pubmed reference: 26586213. DOI: 10.1016/j.tvjl.2015.08.011.
Lu, C.C., Liu, M.M., Culshaw, G., Clinton, M., Argyle, D.J., Corcoran, B.M. :
Gene network and canonical pathway analysis in canine myxomatous mitral valve disease: a microarray study. Vet J 204:23-31, 2015. Pubmed reference: 25841900. DOI: 10.1016/j.tvjl.2015.02.021.
Mattin, M.J., Boswood, A., Church, D.B., McGreevy, P.D., O'Neill, D.G., Thomson, P.C., Brodbelt, D.C. :
Degenerative mitral valve disease: Survival of dogs attending primary-care practice in England. Prev Vet Med 122:436-42, 2015. Pubmed reference: 26058819. DOI: 10.1016/j.prevetmed.2015.05.007.
Reimann, M.J., Ljungvall, I., Hillström, A., Møller, J.E., Hagman, R., Falk, T., Höglund, K., Häggström, J., Olsen, L.H. :
Increased serum C-reactive protein concentrations in dogs with congestive heart failure due to myxomatous mitral valve disease. Vet J :, 2015. Pubmed reference: 26831162. DOI: 10.1016/j.tvjl.2015.12.006.
Stern, J.A., Hsue, W., Song, K.H., Ontiveros, E.S., Luis Fuentes, V., Stepien, R.L. :
Severity of Mitral Valve Degeneration Is Associated with Chromosome 15 Loci in Whippet Dogs. PLoS One 10:e0141234, 2015. Pubmed reference: 26509595. DOI: 10.1371/journal.pone.0141234.
Tidholm, A., Höglund, K., Häggström, J., Ljungvall, I. :
Diagnostic Value of Selected Echocardiographic Variables to Identify Pulmonary Hypertension in Dogs with Myxomatous Mitral Valve Disease. J Vet Intern Med 29:1510-7, 2015. Pubmed reference: 26365438. DOI: 10.1111/jvim.13609.
2014 Reimann, M.J., Møller, J.E., Häggström, J., Markussen, B., Holen, A.E., Falk, T., Olsen, L.H. :
R-R interval variations influence the degree of mitral regurgitation in dogs with myxomatous mitral valve disease. Vet J :, 2014. Pubmed reference: 24507881. DOI: 10.1016/j.tvjl.2014.01.001.
2013 Bellumori, T.P., Famula, T.R., Bannasch, D.L., Belanger, J.M., Oberbauer, A.M. :
Prevalence of inherited disorders among mixed-breed and purebred dogs: 27,254 cases (1995-2010). J Am Vet Med Assoc 242:1549-55, 2013. Pubmed reference: 23683021. DOI: 10.2460/javma.242.11.1549.
Bigg, P.W., Baldo, G., Sleeper, M.M., O'Donnell, P.A., Bai, H., Rokkam, V.R., Liu, Y., Wu, S., Giugliani, R., Casal, M.L., Haskins, M.E., Ponder, K.P. :
Pathogenesis of mitral valve disease in mucopolysaccharidosis VII dogs. Mol Genet Metab 110:319-28, 2013. Pubmed reference: 23856419. DOI: 10.1016/j.ymgme.2013.06.013.
2012 Atkins, C.E., Häggström, J. :
Pharmacologic management of myxomatous mitral valve disease in dogs. J Vet Cardiol 14:165-84, 2012. Pubmed reference: 22386553. DOI: 10.1016/j.jvc.2012.02.002.
Aupperle, H., Disatian, S. :
Pathology, protein expression and signaling in myxomatous mitral valve degeneration: Comparison of dogs and humans. J Vet Cardiol 14:59-71, 2012. Pubmed reference: 22364722. DOI: 10.1016/j.jvc.2012.01.005.
Borgarelli, M., Buchanan, J.W. :
Historical review, epidemiology and natural history of degenerative mitral valve disease. J Vet Cardiol 14:93-101, 2012. Pubmed reference: 22386588. DOI: 10.1016/j.jvc.2012.01.011.
Chetboul, V., Tissier, R. :
Echocardiographic assessment of canine degenerative mitral valve disease. J Vet Cardiol 14:127-48, 2012. Pubmed reference: 22366573. DOI: 10.1016/j.jvc.2011.11.005.
Fox, P.R. :
Pathology of myxomatous mitral valve disease in the dog J Vet Cardiol 14:103-26, 2012. Pubmed reference: 22386587. DOI: 10.1016/j.jvc.2012.02.001.
French, A.T., Ogden, R., Eland, C., Hemani, G., Pong-Wong, R., Corcoran, B., Summers, K.M. :
Genome-wide analysis of mitral valve disease in Cavalier King Charles Spaniels. Vet J 193:283-6, 2012. Pubmed reference: 22050842. DOI: 10.1016/j.tvjl.2011.09.011.
Hezzell, M.J., Boswood, A., Chang, Y.M., Moonarmart, W., Souttar, K., Elliott, J. :
The Combined Prognostic Potential of Serum High-Sensitivity Cardiac Troponin I and N-Terminal pro-B-Type Natriuretic Peptide Concentrations in Dogs with Degenerative Mitral Valve Disease. J Vet Intern Med 26:302-11, 2012. Pubmed reference: 22369312. DOI: 10.1111/j.1939-1676.2012.00894.x.
Parker, H.G., Kilroy-Glynn, P. :
Myxomatous mitral valve disease in dogs: Does size matter? J Vet Cardiol 14:19-29, 2012. Pubmed reference: 22356836. DOI: 10.1016/j.jvc.2012.01.006.
Reynolds, C.A., Brown, D.C., Rush, J.E., Fox, P.R., Nguyenba, T.P., Lehmkuhl, L.B., Gordon, S.G., Kellihan, H.B., Stepien, R.L., Lefbom, B.K., Kate Meier, C., Oyama, M.A. :
Prediction of first onset of congestive heart failure in dogs with degenerative mitral valve disease: The PREDICT cohort study. J Vet Cardiol 14:193-202, 2012. Pubmed reference: 22366568. DOI: 10.1016/j.jvc.2012.01.008.
2011 Borgarelli, M., Crosara, S., Lamb, K., Savarino, P., La Rosa, G., Tarducci, A., Haggstrom, J. :
Survival characteristics and prognostic variables of dogs with preclinical chronic degenerative mitral valve disease attributable to myxomatous degeneration. J Vet Intern Med 26:69-75, 2011. Pubmed reference: 22211523. DOI: 10.1111/j.1939-1676.2011.00860.x.
Lewis, T., Swift, S., Woolliams, JA., Blott, S. :
Heritability of premature mitral valve disease in Cavalier King Charles spaniels. Vet J 188:73-76, 2011. Pubmed reference: 20347358. DOI: 10.1016/j.tvjl.2010.02.016.
Madsen, M.B., Olsen, L.H., Häggström, J., Höglund, K., Ljungvall, I., Falk, T., Wess, G., Stephenson, H., Dukes-McEwan, J., Chetboul, V., Gouni, V., Proschowsky, H.F., Cirera, S., Karlskov-Mortensen, P., Fredholm, M. :
Identification of 2 loci associated with development of myxomatous mitral valve disease in Cavalier King Charles Spaniels. J Hered 102 Suppl 1:S62-7, 2011. Pubmed reference: 21846748. DOI: 10.1093/jhered/esr041.
2010 Borgarelli, M., Haggstrom, J. :
Canine degenerative myxomatous mitral valve disease: natural history, clinical presentation and therapy. Vet Clin North Am Small Anim Pract 40:651-63, 2010. Pubmed reference: 20610017. DOI: 10.1016/j.cvsm.2010.03.008.
Lundin, T., Kvart, C. :
Evaluation of the Swedish breeding program for cavalier King Charles spaniels. Acta Vet Scand 52:54, 2010. Pubmed reference: 20863375. DOI: 10.1186/1751-0147-52-54.
2009 Aupperle, H., Thielebein, J., Kiefer, B., März, I., Dinges, G., Schoon, H.A., Schubert, A. :
Expression of genes encoding matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in normal and diseased canine mitral valves. J Comp Pathol 140:271-7, 2009. Pubmed reference: 19285315. DOI: 10.1016/j.jcpa.2009.01.001.
Chetboul, V., Serres, F., Tissier, R., Lefebvre, HP., Sampedrano, CC., Gouni, V., Poujol, L., Hawa, G., Pouchelon, JL. :
Association of plasma N-terminal pro-B-type natriuretic peptide concentration with mitral regurgitation severity and outcome in dogs with asymptomatic degenerative mitral valve disease. J Vet Intern Med 23:984-94, 2009. Pubmed reference: 19572913. DOI: 10.1111/j.1939-1676.2009.0347.x.
Zheng, J., Chen, Y., Pat, B., Dell'italia, L.A., Tillson, M., Dillon, A.R., Powell, P.C., Shi, K., Shah, N., Denney, T., Husain, A., Dell'Italia, L.J. :
Microarray identifies extensive downregulation of noncollagen extracellular matrix and profibrotic growth factor genes in chronic isolated mitral regurgitation in the dog. Circulation 119:2086-95, 2009. Pubmed reference: 19349319. DOI: 10.1161/CIRCULATIONAHA.108.826230.
2008 Borgarelli, M., Savarino, P., Crosara, S., Santilli, R.A., Chiavegato, D., Poggi, M., Bellino, C., La Rosa, G., Zanatta, R., Haggstrom, J., Tarducci, A. :
Survival characteristics and prognostic variables of dogs with mitral regurgitation attributable to myxomatous valve disease. J Vet Intern Med 22:120-8, 2008. Pubmed reference: 18289298. DOI: 10.1111/j.1939-1676.2007.0008.x.
2006 Oyama, M.A., Chittur, S.V. :
Genomic expression patterns of mitral valve tissues from dogs with degenerative mitral valve disease. Am J Vet Res 67:1307-18, 2006. Pubmed reference: 16881841. DOI: 10.2460/ajvr.67.8.1307.
2004 Borgarelli, M., Zini, E., D'Agnolo, G., Tarducci, A., Santilli, R.A., Chiavegato, D., Tursi, M., Prunotto, M., Häggström, J. :
Comparison of primary mitral valve disease in German Shepherd dogs and in small breeds. J Vet Cardiol 6:27-34, 2004. Pubmed reference: 19083307. DOI: 10.1016/S1760-2734(06)70055-8.
Chetboul, V., Tissier, R., Villaret, F., Nicolle, A., Déan, E., Benalloul, T., Pouchelon, J.L. :
[Epidemiological, clinical, echo-doppler characteristics of mitral valve endocardiosis in Cavalier King Charles in France: a retrospective study of 451 cases (1995 to 2003)]. Can Vet J 45:1012-5, 2004. Pubmed reference: 15646848.
Häggström, J., Duelund Pedersen, H., Kvart, C. :
New insights into degenerative mitral valve disease in dogs. Vet Clin North Am Small Anim Pract 34:1209-26, vii-viii, 2004. Pubmed reference: 15325478. DOI: 10.1016/j.cvsm.2004.05.002.
Tarnow, I., Kristensen, AT., Olsen, LH., Pedersen, HD. :
Assessment of changes in hemostatic markers in Cavalier King Charles Spaniels with myxomatous mitral valve disease. Am J Vet Res 65:1644-52, 2004. Pubmed reference: 15631028.
2003 Kvart, C., Haggstrom, J., Pedersen, H.D. :
[ACE inhibitors in dogs with subclinical chronic mitral insufficiency] Tijdschrift voor Diergeneeskunde 128:76-7, 2003. Pubmed reference: 12616901.
Olsen, L.H., Martinussen, T., Pedersen, H.D. :
Early echocardiographic predictors of myxomatous mitral valve disease in dachshunds Veterinary Record 152:293-7, 2003. Pubmed reference: 12650472.
2002 Hagel, T., Deinert, M., Distl, O. :
Chronic mitral valve insufficiency in the cavalier King Charles spaniel Praktische Tierarzt 83:1056-+, 2002.
2001 Olsen, L.H., Kristensen, A.T., Haggstrom, J., Jensen, A.L., Klitgaard, B., Hansson, H., Pedersen, H.D. :
Increased platelet aggregation response in cavalier king charles spaniels with mitral valve prolapse Journal of Veterinary Internal Medicine 15:209-216, 2001. Pubmed reference: 11380029.
1999 Olsen, L.H., Fredholm, M., Pedersen, H.D. :
Epidemiology and inheritance of mitral valve prolapse in Dachshunds Journal of Veterinary Internal Medicine 13:448-456, 1999. Pubmed reference: 10499729.
Pedersen, H.D., Lorentzen, K.A., Kristensen, B.O. :
Echocardiographic mitral valve prolapse in cavalier King Charles spaniels: epidemiology and prognostic significance for regurgitation Veterinary Record 144:315-320, 1999. Pubmed reference: 10212505.
1998 Delpalacio, M.J.F., Bayon, A., Bernal, L.J., Ceron, J.J., Navarro, J.A. :
Clinical and pathological findings of severe subvalvular aortic stenosis and mitral dysplasia in a rottweiler puppy Journal of Small Animal Practice 39:481-485, 1998. Pubmed reference: 9816571.
1997 Tidholm, A. :
Retrospective study of congenital heart defects in 151 dogs Journal of Small Animal Practice 38:94-98, 1997. Pubmed reference: 9097239.
1996 Kosztolich, A. :
Clinical-cardiological examinations of the mitral-valve insufficiency in the dog [German] Kleintierpraxis 41:705 ff., 1996.
Pedersen, H.D., Kristensen, B.O., Norby, B., Lorentzen, K.A. :
Echocardiographic study of mitral valve prolapse in dachshunds Journal of Veterinary Medicine - Series A 43:103-110, 1996. Pubmed reference: 8701631.
Swenson, L., Häggström, J., Kvart, C., Juneja, R.K. :
Relationship between parental cardiac status in Cavalier King Charles spaniels and prevalence and severity of chronic valvular disease in offspring. J Am Vet Med Assoc 208:2009-12, 1996. Pubmed reference: 8707674.
1994 Jones, M. :
Mitral Valve Disease in Cavalier King Charles Spaniels Veterinary Record 134:72, 1994. Pubmed reference: 8135022.
1993 Beardow, AW., Buchanan, JW. :
Chronic mitral valve disease in cavalier King Charles spaniels: 95 cases (1987-1991) J Am Vet Med Assoc 203:1023-9, 1993. Pubmed reference: 8135932.
1992 Haggstrom, J., Hansson, K., Kvart, C., Swenson, L. :
Chronic Valvular Disease in the Cavalier King Charles Spaniel in Sweden Veterinary Record 131:549-553, 1992. Pubmed reference: 1481344.
Malik, R., Hunt, G.B., Allan, G.S. :
Prevalence of Mitral Valve Insufficiency in Cavalier King Charles Spaniels Veterinary Record 130:302-303, 1992. Pubmed reference: 1595150.
1973 Mulvihill, J.J., Priester, W.A. :
Congenital heart disease in dogs: epidemiologic similarities to man. Teratology 7:73-7, 1973. Pubmed reference: 4693746. DOI: 10.1002/tera.1420070111.

Edit History

  • Created by Frank Nicholas on 06 Sep 2005
  • Changed by Frank Nicholas on 03 Sep 2011
  • Changed by Frank Nicholas on 07 Sep 2011
  • Changed by Frank Nicholas on 20 May 2013