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Aortic valve disease 2(AOVD2)

MedGen UID:
762200
Concept ID:
C3542024
Disease or Syndrome
Synonym: AOVD2
 
Gene (location): SMAD6 (15q22.31)
 
Monarch Initiative: MONDO:0013902
OMIM®: 614823

Definition

Any aortic valve disease in which the cause of the disease is a mutation in the SMAD6 gene. [from MONDO]

Clinical features

From HPO
Aortic aneurysm
MedGen UID:
362
Concept ID:
C0003486
Disease or Syndrome
Aortic dilatation refers to a dimension that is greater than the 95th percentile for the normal person age, sex and body size. In contrast, an aneurysm is defined as a localized dilation of the aorta that is more than 150 percent of predicted (ratio of observed to expected diameter 1.5 or more). Aneurysm should be distinguished from ectasia, which represents a diffuse dilation of the aorta less than 50 percent of normal aorta diameter.
Coarctation of aorta
MedGen UID:
1617
Concept ID:
C0003492
Congenital Abnormality
Coarctation of the aorta is a narrowing or constriction of a segment of the aorta.
Aortic regurgitation
MedGen UID:
8153
Concept ID:
C0003504
Disease or Syndrome
An insufficiency of the aortic valve, leading to regurgitation (backward flow) of blood from the aorta into the left ventricle.
Aortic valve stenosis
MedGen UID:
1621
Concept ID:
C0003507
Pathologic Function
The presence of a stenosis (narrowing) of the aortic valve.
Patent foramen ovale
MedGen UID:
8891
Concept ID:
C0016522
Congenital Abnormality
Failure of the foramen ovale to seal postnatally, leaving a potential conduit between the left and right cardiac atria.
Mitral regurgitation
MedGen UID:
7670
Concept ID:
C0026266
Disease or Syndrome
An abnormality of the mitral valve characterized by insufficiency or incompetence of the mitral valve resulting in retrograde leaking of blood through the mitral valve upon ventricular contraction.
Bicuspid aortic valve
MedGen UID:
57436
Concept ID:
C0149630
Congenital Abnormality
Aortic valve disease-2 (AOVD2) is characterized by bicuspid aortic valve (BAV) and dilation of the ascending aorta. Calcification of the valve and the aorta has been observed, and some patients exhibit coarctation of the aorta (Tan et al., 2012; Luyckx et al., 2019; Park et al., 2019). For a general phenotypic description and a discussion of genetic heterogeneity of aortic valve disease, see AOVD1 (109730).
Calcification of the aorta
MedGen UID:
202111
Concept ID:
C1096249
Pathologic Function
Calcification, that is, pathological deposition of calcium salts in the aorta.
Ascending aortic dissection
MedGen UID:
322966
Concept ID:
C1836653
Disease or Syndrome
A separation of the layers within the wall of the ascending aorta. Tears in the intimal layer result in the propagation of dissection (proximally or distally) secondary to blood entering the intima-media space.
Pulmonic stenosis
MedGen UID:
408291
Concept ID:
C1956257
Disease or Syndrome
A narrowing of the right ventricular outflow tract that can occur at the pulmonary valve (valvular stenosis), below the pulmonary valve (infundibular stenosis), or above the pulmonary valve (supravalvar stenosis).
Aortic tortuosity
MedGen UID:
870555
Concept ID:
C4025003
Anatomical Abnormality
Abnormal tortuous (i.e., twisted) form of the aorta.

Professional guidelines

PubMed

Lauder L, Mahfoud F, Azizi M, Bhatt DL, Ewen S, Kario K, Parati G, Rossignol P, Schlaich MP, Teo KK, Townsend RR, Tsioufis C, Weber MA, Weber T, Böhm M
Eur Heart J 2023 Jun 20;44(23):2066-2077. doi: 10.1093/eurheartj/ehac395. PMID: 36342266
Michelena HI, Della Corte A, Evangelista A, Maleszewski JJ, Edwards WD, Roman MJ, Devereux RB, Fernández B, Asch FM, Barker AJ, Sierra-Galan LM, De Kerchove L, Fernandes SM, Fedak PWM, Girdauskas E, Delgado V, Abbara S, Lansac E, Prakash SK, Bissell MM, Popescu BA, Hope MD, Sitges M, Thourani VH, Pibarot P, Chandrasekaran K, Lancellotti P, Borger MA, Forrest JK, Webb J, Milewicz DM, Makkar R, Leon MB, Sanders SP, Markl M, Ferrari VA, Roberts WC, Song JK, Blanke P, White CS, Siu S, Svensson LG, Braverman AC, Bavaria J, Sundt TM, El Khoury G, De Paulis R, Enriquez-Sarano M, Bax JJ, Otto CM, Schäfers HJ; Endorsed by the Heart Valve Society (HVS), European Association of Cardiovascular Imaging (EACVI), Society of Thoracic Surgeons (STS), American Association for Thoracic Surgery (AATS), Society for Cardiovascular Magnetic Resonance (SCMR), Society of Cardiovascular Computed Tomography (SCCT), North American Society for Cardiovascular Imaging (NASCI) and the International Bicuspid Aortic Valve Consortium (BAVCon)
Eur J Cardiothorac Surg 2021 Sep 11;60(3):448-476. doi: 10.1093/ejcts/ezab038. PMID: 34293102
Writing Committee Members, Otto CM, Nishimura RA, Bonow RO, Carabello BA, Erwin JP 3rd, Gentile F, Jneid H, Krieger EV, Mack M, McLeod C, O'Gara PT, Rigolin VH, Sundt TM 3rd, Thompson A, Toly C; ACC/AHA Joint Committee Members, O'Gara PT, Beckman JA, Levine GN, Al-Khatib SM, Armbruster A, Birtcher KK, Ciggaroa J, Deswal A, Dixon DL, Fleisher LA, de las Fuentes L, Gentile F, Goldberger ZD, Gorenek B, Haynes N, Hernandez AF, Hlatky MA, Joglar JA, Jones WS, Marine JE, Mark D, Palaniappan L, Piano MR, Spatz ES, Tamis-Holland J, Wijeysundera DN, Woo YJ
J Thorac Cardiovasc Surg 2021 Aug;162(2):e183-e353. Epub 2021 May 8 doi: 10.1016/j.jtcvs.2021.04.002. PMID: 33972115

Recent clinical studies

Etiology

Hao QY, Zeng YH, Lin Y, Guo JB, Li SC, Yang PZ, Gao JW, Li ZH
Front Endocrinol (Lausanne) 2024;15:1421642. Epub 2024 Jul 9 doi: 10.3389/fendo.2024.1421642. PMID: 39045267Free PMC Article
Jørgensen TH, Thyregod HGH, Savontaus M, Willemen Y, Bleie Ø, Tang M, Niemela M, Angerås O, Gudmundsdóttir IJ, Sartipy U, Dagnegaard H, Laine M, Rück A, Piuhola J, Petursson P, Christiansen EH, Malmberg M, Olsen PS, Haaverstad R, Sondergaard L, De Backer O; NOTION-2 investigators
Eur Heart J 2024 Oct 5;45(37):3804-3814. doi: 10.1093/eurheartj/ehae331. PMID: 38747246
Beaver T, Bavaria JE, Griffith B, Svensson LG, Pibarot P, Borger MA, Sharaf OM, Heimansohn DA, Thourani VH, Blackstone EH, Puskas JD; COMMENCE Trial Investigators
J Thorac Cardiovasc Surg 2024 Sep;168(3):781-791. Epub 2023 Sep 29 doi: 10.1016/j.jtcvs.2023.09.047. PMID: 37778503
Verma R, Cohen G, Colbert J, Fedak PWM
Curr Opin Cardiol 2023 Mar 1;38(2):61-67. Epub 2022 Dec 29 doi: 10.1097/HCO.0000000000001020. PMID: 36718616
Siu SC, Silversides CK
J Am Coll Cardiol 2010 Jun 22;55(25):2789-800. doi: 10.1016/j.jacc.2009.12.068. PMID: 20579534

Diagnosis

Li Z, Cheng S, Guo B, Ding L, Liang Y, Shen Y, Li J, Hu Y, Long T, Guo X, Ge J, Gao R, Pibarot P, Zhang B, Xu H, Clavel MA, Wu Y
Eur Heart J 2025 Feb 14;46(7):649-664. doi: 10.1093/eurheartj/ehae406. PMID: 38953786Free PMC Article
Verma R, Cohen G, Colbert J, Fedak PWM
Curr Opin Cardiol 2023 Mar 1;38(2):61-67. Epub 2022 Dec 29 doi: 10.1097/HCO.0000000000001020. PMID: 36718616
Michelena HI, Della Corte A, Evangelista A, Maleszewski JJ, Edwards WD, Roman MJ, Devereux RB, Fernández B, Asch FM, Barker AJ, Sierra-Galan LM, De Kerchove L, Fernandes SM, Fedak PWM, Girdauskas E, Delgado V, Abbara S, Lansac E, Prakash SK, Bissell MM, Popescu BA, Hope MD, Sitges M, Thourani VH, Pibarot P, Chandrasekaran K, Lancellotti P, Borger MA, Forrest JK, Webb J, Milewicz DM, Makkar R, Leon MB, Sanders SP, Markl M, Ferrari VA, Roberts WC, Song JK, Blanke P, White CS, Siu S, Svensson LG, Braverman AC, Bavaria J, Sundt TM, El Khoury G, De Paulis R, Enriquez-Sarano M, Bax JJ, Otto CM, Schäfers HJ
J Thorac Cardiovasc Surg 2021 Sep;162(3):e383-e414. Epub 2021 Jul 22 doi: 10.1016/j.jtcvs.2021.06.019. PMID: 34304896
Tsimikas S, Fazio S, Ferdinand KC, Ginsberg HN, Koschinsky ML, Marcovina SM, Moriarty PM, Rader DJ, Remaley AT, Reyes-Soffer G, Santos RD, Thanassoulis G, Witztum JL, Danthi S, Olive M, Liu L
J Am Coll Cardiol 2018 Jan 16;71(2):177-192. doi: 10.1016/j.jacc.2017.11.014. PMID: 29325642Free PMC Article
Siu SC, Silversides CK
J Am Coll Cardiol 2010 Jun 22;55(25):2789-800. doi: 10.1016/j.jacc.2009.12.068. PMID: 20579534

Therapy

Jørgensen TH, Thyregod HGH, Savontaus M, Willemen Y, Bleie Ø, Tang M, Niemela M, Angerås O, Gudmundsdóttir IJ, Sartipy U, Dagnegaard H, Laine M, Rück A, Piuhola J, Petursson P, Christiansen EH, Malmberg M, Olsen PS, Haaverstad R, Sondergaard L, De Backer O; NOTION-2 investigators
Eur Heart J 2024 Oct 5;45(37):3804-3814. doi: 10.1093/eurheartj/ehae331. PMID: 38747246
Liu Z, Wang K, Jiang C, Chen Y, Liu F, Xie M, Yim WY, Yao D, Qian X, Chen S, Shi J, Xu K, Wang Y, Dong N
Adv Sci (Weinh) 2024 May;11(20):e2307319. Epub 2024 Mar 19 doi: 10.1002/advs.202307319. PMID: 38502885Free PMC Article
Bishev D, Fabara S, Loseke I, Alok A, Al-Ani H, Bazikian Y
Heart Lung Circ 2023 Sep;32(9):1049-1056. Epub 2023 Jul 14 doi: 10.1016/j.hlc.2023.05.019. PMID: 37453852
Diederichsen ACP, Lindholt JS, Möller S, Øvrehus KA, Auscher S, Lambrechtsen J, Hosbond SE, Alan DH, Urbonaviciene G, Becker SW, Fredgart MH, Hasific S, Folkestad L, Gerke O, Rasmussen LM, Møller JE, Mickley H, Dahl JS
Circulation 2022 May 3;145(18):1387-1397. Epub 2022 Apr 25 doi: 10.1161/CIRCULATIONAHA.121.057008. PMID: 35465686Free PMC Article
Amat-Santos IJ, Sánchez-Luna JP, Abu-Assi E, Melendo-Viu M, Cruz-Gonzalez I, Nombela-Franco L, Muñoz-Garcí AJ, Blas SG, de la Torre Hernandez JM, Romaguera R, Sánchez-Recalde Á, Diez-Gil JL, Lopez-Otero D, Gheorge L, Ibáñez B, Iñiguez-Romo A, Raposeiras-Roubín S; Dapagliflozin after Transcatheter Aortic Valve Implantation (DapaTAVI) Investigators
Eur J Heart Fail 2022 Mar;24(3):581-588. Epub 2021 Nov 9 doi: 10.1002/ejhf.2370. PMID: 34693613

Prognosis

Verbrugge FH, Reddy YNV, Eleid MF, Lin G, Burkhoff D, Borlaug BA
Open Heart 2021 Oct;8(2) doi: 10.1136/openhrt-2021-001701. PMID: 34670831Free PMC Article
Yoon SH, Kim WK, Dhoble A, Milhorini Pio S, Babaliaros V, Jilaihawi H, Pilgrim T, De Backer O, Bleiziffer S, Vincent F, Shmidt T, Butter C, Kamioka N, Eschenbach L, Renker M, Asami M, Lazkani M, Fujita B, Birs A, Barbanti M, Pershad A, Landes U, Oldemeyer B, Kitamura M, Oakley L, Ochiai T, Chakravarty T, Nakamura M, Ruile P, Deuschl F, Berman D, Modine T, Ensminger S, Kornowski R, Lange R, McCabe JM, Williams MR, Whisenant B, Delgado V, Windecker S, Van Belle E, Sondergaard L, Chevalier B, Mack M, Bax JJ, Leon MB, Makkar RR; Bicuspid Aortic Valve Stenosis Transcatheter Aortic Valve Replacement Registry Investigators
J Am Coll Cardiol 2020 Sep 1;76(9):1018-1030. doi: 10.1016/j.jacc.2020.07.005. PMID: 32854836
Fernández B, Soto-Navarrete MT, López-García A, López-Unzu MÁ, Durán AC, Fernández MC
Vet Pathol 2020 Mar;57(2):321-331. Epub 2020 Feb 21 doi: 10.1177/0300985819900018. PMID: 32079504
Siu SC, Silversides CK
J Am Coll Cardiol 2010 Jun 22;55(25):2789-800. doi: 10.1016/j.jacc.2009.12.068. PMID: 20579534
Feldman T
Curr Opin Cardiol 1996 Mar;11(2):126-30. doi: 10.1097/00001573-199603000-00005. PMID: 8736683

Clinical prediction guides

Jørgensen TH, Thyregod HGH, Savontaus M, Willemen Y, Bleie Ø, Tang M, Niemela M, Angerås O, Gudmundsdóttir IJ, Sartipy U, Dagnegaard H, Laine M, Rück A, Piuhola J, Petursson P, Christiansen EH, Malmberg M, Olsen PS, Haaverstad R, Sondergaard L, De Backer O; NOTION-2 investigators
Eur Heart J 2024 Oct 5;45(37):3804-3814. doi: 10.1093/eurheartj/ehae331. PMID: 38747246
Beaver T, Bavaria JE, Griffith B, Svensson LG, Pibarot P, Borger MA, Sharaf OM, Heimansohn DA, Thourani VH, Blackstone EH, Puskas JD; COMMENCE Trial Investigators
J Thorac Cardiovasc Surg 2024 Sep;168(3):781-791. Epub 2023 Sep 29 doi: 10.1016/j.jtcvs.2023.09.047. PMID: 37778503
Verma R, Cohen G, Colbert J, Fedak PWM
Curr Opin Cardiol 2023 Mar 1;38(2):61-67. Epub 2022 Dec 29 doi: 10.1097/HCO.0000000000001020. PMID: 36718616
He JJ, Xiong TY, Yao YJ, Peng Y, Wei JF, He S, Chen Y, Li Q, Zhao ZG, Wei X, Zhou WX, Liang YJ, Tang H, Chen G, Zhou X, Zheng MX, Meng W, Liao YB, Li YJ, Li YM, Chen F, Ou YW, Liu Q, Li X, Wang X, Zhang Y, Zhu ZK, Yang HR, Jia KY, Chen M, Feng Y
JACC Cardiovasc Interv 2022 Aug 22;15(16):1652-1660. doi: 10.1016/j.jcin.2022.06.036. PMID: 35981839
Michelena HI, Della Corte A, Evangelista A, Maleszewski JJ, Edwards WD, Roman MJ, Devereux RB, Fernández B, Asch FM, Barker AJ, Sierra-Galan LM, De Kerchove L, Fernandes SM, Fedak PWM, Girdauskas E, Delgado V, Abbara S, Lansac E, Prakash SK, Bissell MM, Popescu BA, Hope MD, Sitges M, Thourani VH, Pibarot P, Chandrasekaran K, Lancellotti P, Borger MA, Forrest JK, Webb J, Milewicz DM, Makkar R, Leon MB, Sanders SP, Markl M, Ferrari VA, Roberts WC, Song JK, Blanke P, White CS, Siu S, Svensson LG, Braverman AC, Bavaria J, Sundt TM, El Khoury G, De Paulis R, Enriquez-Sarano M, Bax JJ, Otto CM, Schäfers HJ
J Thorac Cardiovasc Surg 2021 Sep;162(3):e383-e414. Epub 2021 Jul 22 doi: 10.1016/j.jtcvs.2021.06.019. PMID: 34304896

Recent systematic reviews

Généreux P, Banovic M, Kang DH, Giustino G, Prendergast BD, Lindman BR, Newby DE, Pibarot P, Redfors B, Craig NJ, Bartunek J, Schwartz A, Seyedin R, Cohen DJ, Iung B, Leon MB, Dweck MR
J Am Coll Cardiol 2025 Mar 11;85(9):912-922. Epub 2024 Nov 18 doi: 10.1016/j.jacc.2024.11.006. PMID: 39641732
Arsenault BJ, Loganath K, Girard A, Botezatu S, Zheng KH, Tzolos E, Abdoun K, Tastet L, Capoulade R, Côté N, Craig N, Chan KL, Tam JW, Teo KK, Couture C, Clavel MA, Mathieu P, Thériault S, Stroes ESG, Newby DE, Tsimikas S, Pibarot P, Dweck MR
JAMA Cardiol 2024 Sep 1;9(9):835-842. doi: 10.1001/jamacardio.2024.1882. PMID: 39018080Free PMC Article
Tabrizi NS, Demos RA, Schumann R, Musuku SR, Shapeton AD
J Cardiothorac Vasc Anesth 2024 Feb;38(2):505-516. Epub 2023 Sep 24 doi: 10.1053/j.jvca.2023.09.027. PMID: 37880038
Yokoyama Y, Kuno T, Toyoda N, Fujisaki T, Takagi H, Itagaki S, Ibrahim M, Ouzounian M, El-Hamamsy I, Fukuhara S
J Am Heart Assoc 2023 Jan 3;12(1):e8066. Epub 2022 Dec 24 doi: 10.1161/JAHA.122.027715. PMID: 36565200Free PMC Article
Swift SL, Puehler T, Misso K, Lang SH, Forbes C, Kleijnen J, Danner M, Kuhn C, Haneya A, Seoudy H, Cremer J, Frey N, Lutter G, Wolff R, Scheibler F, Wehkamp K, Frank D
BMJ Open 2021 Dec 6;11(12):e054222. doi: 10.1136/bmjopen-2021-054222. PMID: 34873012Free PMC Article

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