Metabolic Determinants of the Progression of Aortic Stenosis

NCT01679431 | Unknown

• 1 other identifier: MOP-114997
• Study Type: observational
• Target: 250
• Locations: 1 country
• Sites: 1

Brief Summary

Calcific aortic stenosis (AS) has become the most common cardiac disease after coronary artery disease and hypertension. Unfortunately no medical therapies have been proven to decrease either the progression of valve stenosis or the resulting adverse effects on myocardial remodeling and function. In light of the studies performed in PROGRESSA, it becomes obvious that: i) AS is a complex and actively regulated process that involves the interaction of several pathways including lipid infiltration and retention, chronic inflammation, osteogenic activation, and active mineralization within the valvular tissues; ii) AS is not a disease strictly limited to the aortic valve but rather a systemic disease that often involves calcification and stiffening of the aorta and impairment of LV function as a consequence of pressure overload. Our findings suggest that the dysmetabolic milieu linked to visceral obesity may accelerate the deterioration of the structure and function not only of the aortic valve but also of the aorta and of the left ventricle. These findings open new avenues of research and provide strong impetus for the elaboration of prospective studies focusing on the "valvulo-metabolic risk" in AS. The general hypotheses are: The metabolic abnormalities linked to visceral obesity accelerate (1) the progression of valvular calcification and stenosis, aortic calcification and stiffness; (2) the progression of myocardial fibrosis and dysfunction. The general objectives of the study are to elucidate the mechanisms implicated in the pathogenesis of AS and to identify the metabolic factors that determine the progression of: i) aortic valve calcification and stenosis; ii) myocardial fibrosis and dysfunction; and iii) clinical outcomes. This study will contribute to identifying the key metabolic determinants of AS progression and will pave the way for the future development of non surgical therapies for this disease. The results of this study would provide strong support to the realization of randomized trial to test the efficacy of lifestyle modification program or new pharmacological treatment aiming at the reduction of visceral fat and associated metabolic abnormalities in the AS population. Furthermore, this study will contribute to the identification of novel blood and imaging biomarkers of faster disease progression, which will help to optimize risk stratification and timing of AVR in the AS population.

Conditions

Aortic Valve Stenosis

Keywords

Aortic Stenosis; Obesity, Abdominal; Metabolic Syndrome X; Insulin Resistance; Echocardiography, Doppler; Multidetector Computed Tomography; Magnetic Resonance Imaging

Outcome Measures

Primary Outcomes (1)

• Progression of aortic valve stenosis

  Annualized progression rate of aortic stenosis hemodynamic severity calculate as the difference between peak aortic jet velocity, transvalvular gradients, and aortic valve area measured at baseline and those measured at the last follow-up divided by the time between the first and last examinations.

  Patients will be followed every 1 year, up to 5 years

Secondary Outcomes (2)

• Progression of aortic valve calcification

  Patients will be followed every 2 years, up to 5 years

• Progression of myocardial fibrosis and dysfunction

  PPatients will be followed every 2 years, up to 5 years

Other Outcomes (6)

• Progression of aortic calcification and stiffness

  Patients will be followed every 2 years, up to 5 years

• Progression of coronary artery calcification

  Patients will be followed every 2 years, up to 5 years

• Progression of global hemodynamic load

  Patients will be followed every 1 year, up to 5 years

Study Arms (1)

Patients with aortic stenosis

Patients have every year: 1) an assessment of cardiometabolic risk profile with measure of body mass index, waist circumference and fasting blood sample and 2) a comprehensive Doppler-echocardiography exam. Computed tomography and magnetic resonance imaging are performed every 2 years.

Diagnostic Test: Doppler-echocardiography; Radiation: Computed tomography; Other: Magnetic resonance imaging; Biological: Fasting blood sample

Interventions

Doppler-echocardiography DIAGNOSTIC_TEST

Patients with aortic stenosis

Computed tomography RADIATION

Patients with aortic stenosis

Magnetic resonance imaging OTHER

Patients with aortic stenosis

Fasting blood sample BIOLOGICAL

Patients with aortic stenosis

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Cohort will be selected at primary care clinic

You may qualify if:

• Age \>21 years
• Presence of aortic stenosis defined as peak aortic jet velocity ≥2.5 m/s

You may not qualify if:

• Symptomatic aortic stenosis
• Very severe aortic stenosis defined as an AVA≤0.6 cm2
• Left ventricular ejection fraction \< 50%
• More than mild aortic or mitral regurgitation, or mitral stenosis
• Atrial fibrillation or flutter
• Pregnant or lactating women
• Contraindications to gadolinium-enhanced MRI

Sponsors & Collaborators

• Laval University: lead
• Canadian Institutes of Health Research (CIHR): collaborator
• Heart and Stroke Foundation of Canada: collaborator

Study Sites (1)

Institut Universitaire de Cardiologie et de Pneumologie de Québec

Québec, G1V4G5, Canada

RECRUITING

Related Publications (58)

• Capoulade R, Clavel MA, Dumesnil JG, Chan KL, Teo KK, Tam JW, Cote N, Mathieu P, Despres JP, Pibarot P; ASTRONOMER Investigators. Impact of metabolic syndrome on progression of aortic stenosis: influence of age and statin therapy. J Am Coll Cardiol. 2012 Jul 17;60(3):216-23. doi: 10.1016/j.jacc.2012.03.052.

  PMID: 22789885 BACKGROUND

• Cote N, El Husseini D, Pepin A, Bouvet C, Gilbert LA, Audet A, Fournier D, Pibarot P, Moreau P, Mathieu P. Inhibition of ectonucleotidase with ARL67156 prevents the development of calcific aortic valve disease in warfarin-treated rats. Eur J Pharmacol. 2012 Aug 15;689(1-3):139-46. doi: 10.1016/j.ejphar.2012.05.016. Epub 2012 May 31.

  PMID: 22659116 BACKGROUND

• Audet A, Cote N, Couture C, Bosse Y, Despres JP, Pibarot P, Mathieu P. Amyloid substance within stenotic aortic valves promotes mineralization. Histopathology. 2012 Oct;61(4):610-9. doi: 10.1111/j.1365-2559.2012.04265.x.

  PMID: 22642224 BACKGROUND

• Carter S, Miard S, Roy-Bellavance C, Boivin L, Li Z, Pibarot P, Mathieu P, Picard F. Sirt1 inhibits resistin expression in aortic stenosis. PLoS One. 2012;7(4):e35110. doi: 10.1371/journal.pone.0035110. Epub 2012 Apr 6.

  PMID: 22493735 BACKGROUND

• Shetty R, Girerd N, Cote N, Arsenault B, Despres JP, Pibarot P, Mathieu P. Elevated proportion of small, dense low-density lipoprotein particles and lower adiponectin blood levels predict early structural valve degeneration of bioprostheses. Cardiology. 2012;121(1):20-6. doi: 10.1159/000336170. Epub 2012 Feb 25.

  PMID: 22378142 BACKGROUND

• Cote N, El Husseini D, Pepin A, Guauque-Olarte S, Ducharme V, Bouchard-Cannon P, Audet A, Fournier D, Gaudreault N, Derbali H, McKee MD, Simard C, Despres JP, Pibarot P, Bosse Y, Mathieu P. ATP acts as a survival signal and prevents the mineralization of aortic valve. J Mol Cell Cardiol. 2012 May;52(5):1191-202. doi: 10.1016/j.yjmcc.2012.02.003. Epub 2012 Feb 16.

  PMID: 22366713 BACKGROUND

• Cote N, Couture C, Pibarot P, Despres JP, Mathieu P. Angiotensin receptor blockers are associated with a lower remodelling score of stenotic aortic valves. Eur J Clin Invest. 2011 Nov;41(11):1172-9. doi: 10.1111/j.1365-2362.2011.02522.x.

  PMID: 21988540 BACKGROUND

• Gaudreault N, Ducharme V, Lamontagne M, Guauque-Olarte S, Mathieu P, Pibarot P, Bosse Y. Replication of genetic association studies in aortic stenosis in adults. Am J Cardiol. 2011 Nov 1;108(9):1305-10. doi: 10.1016/j.amjcard.2011.06.050. Epub 2011 Aug 18.

  PMID: 21855833 BACKGROUND

• Mohty D, Pibarot P, Cote N, Cartier A, Audet A, Despres JP, Mathieu P. Hypoadiponectinemia is associated with valvular inflammation and faster disease progression in patients with aortic stenosis. Cardiology. 2011;118(2):140-6. doi: 10.1159/000327588. Epub 2011 May 19.

  PMID: 21597293 BACKGROUND

• Page A, Dumesnil JG, Clavel MA, Chan KL, Teo KK, Tam JW, Mathieu P, Despres JP, Pibarot P; ASTRONOMER Investigators. Metabolic syndrome is associated with more pronounced impairment of left ventricle geometry and function in patients with calcific aortic stenosis: a substudy of the ASTRONOMER (Aortic Stenosis Progression Observation Measuring Effects of Rosuvastatin). J Am Coll Cardiol. 2010 Apr 27;55(17):1867-74. doi: 10.1016/j.jacc.2009.11.083.

  PMID: 20413039 BACKGROUND

• Derbali H, Bosse Y, Cote N, Pibarot P, Audet A, Pepin A, Arsenault B, Couture C, Despres JP, Mathieu P. Increased biglycan in aortic valve stenosis leads to the overexpression of phospholipid transfer protein via Toll-like receptor 2. Am J Pathol. 2010 Jun;176(6):2638-45. doi: 10.2353/ajpath.2010.090541. Epub 2010 Apr 9.

  PMID: 20382708 BACKGROUND

• Bosse Y, Miqdad A, Fournier D, Pepin A, Pibarot P, Mathieu P. Refining molecular pathways leading to calcific aortic valve stenosis by studying gene expression profile of normal and calcified stenotic human aortic valves. Circ Cardiovasc Genet. 2009 Oct;2(5):489-98. doi: 10.1161/CIRCGENETICS.108.820795. Epub 2009 Jul 8.

  PMID: 20031625 BACKGROUND

• Cote N, Pibarot P, Pepin A, Fournier D, Audet A, Arsenault B, Couture C, Poirier P, Despres JP, Mathieu P. Oxidized low-density lipoprotein, angiotensin II and increased waist cirumference are associated with valve inflammation in prehypertensive patients with aortic stenosis. Int J Cardiol. 2010 Dec 3;145(3):444-9. doi: 10.1016/j.ijcard.2009.05.054. Epub 2009 Jun 13.

  PMID: 19525020 BACKGROUND

• Mohty D, Pibarot P, Despres JP, Cartier A, Arsenault B, Picard F, Mathieu P. Age-related differences in the pathogenesis of calcific aortic stenosis: the potential role of resistin. Int J Cardiol. 2010 Jul 9;142(2):126-32. doi: 10.1016/j.ijcard.2008.12.068. Epub 2009 Jan 21.

  PMID: 19162347 BACKGROUND

• Mathieu P, Despres JP, Pibarot P. The 'valvulo-metabolic' risk in calcific aortic valve disease. Can J Cardiol. 2007 Oct;23 Suppl B(Suppl B):32B-39B. doi: 10.1016/s0828-282x(07)71008-5.

  PMID: 17932585 BACKGROUND

• Mohty D, Pibarot P, Despres JP, Cote C, Arsenault B, Cartier A, Cosnay P, Couture C, Mathieu P. Association between plasma LDL particle size, valvular accumulation of oxidized LDL, and inflammation in patients with aortic stenosis. Arterioscler Thromb Vasc Biol. 2008 Jan;28(1):187-93. doi: 10.1161/ATVBAHA.107.154989. Epub 2007 Nov 1.

  PMID: 17975118 BACKGROUND

• Cote C, Pibarot P, Despres JP, Mohty D, Cartier A, Arsenault BJ, Couture C, Mathieu P. Association between circulating oxidised low-density lipoprotein and fibrocalcific remodelling of the aortic valve in aortic stenosis. Heart. 2008 Sep;94(9):1175-80. doi: 10.1136/hrt.2007.125740. Epub 2007 Oct 11.

  PMID: 17932090 BACKGROUND

• Pibarot P, Dumesnil JG, Mathieu P. [New insight into the treatment of aortic stenosis]. Med Sci (Paris). 2007 Jan;23(1):81-7. doi: 10.1051/medsci/200723181. French.

  PMID: 17212936 BACKGROUND

• Briand M, Lemieux I, Dumesnil JG, Mathieu P, Cartier A, Despres JP, Arsenault M, Couet J, Pibarot P. Metabolic syndrome negatively influences disease progression and prognosis in aortic stenosis. J Am Coll Cardiol. 2006 Jun 6;47(11):2229-36. doi: 10.1016/j.jacc.2005.12.073. Epub 2006 May 15.

  PMID: 16750688 BACKGROUND

• Charest A, Pepin A, Shetty R, Cote C, Voisine P, Dagenais F, Pibarot P, Mathieu P. Distribution of SPARC during neovascularisation of degenerative aortic stenosis. Heart. 2006 Dec;92(12):1844-9. doi: 10.1136/hrt.2005.086595. Epub 2006 May 18.

  PMID: 16709694 BACKGROUND

• Shetty R, Pepin A, Charest A, Perron J, Doyle D, Voisine P, Dagenais F, Pibarot P, Mathieu P. Expression of bone-regulatory proteins in human valve allografts. Heart. 2006 Sep;92(9):1303-8. doi: 10.1136/hrt.2005.075903. Epub 2006 Jan 31.

  PMID: 16449517 BACKGROUND

• Briand M, Dumesnil JG, Kadem L, Tongue AG, Rieu R, Garcia D, Pibarot P. Reduced systemic arterial compliance impacts significantly on left ventricular afterload and function in aortic stenosis: implications for diagnosis and treatment. J Am Coll Cardiol. 2005 Jul 19;46(2):291-8. doi: 10.1016/j.jacc.2004.10.081.

  PMID: 16022957 BACKGROUND

• Tastet L, Capoulade R, Shen M, Clavel MA, Cote N, Mathieu P, Arsenault M, Bedard E, Tremblay A, Samson M, Bosse Y, Dumesnil JG, Arsenault BJ, Beaudoin J, Bernier M, Despres JP, Pibarot P. ApoB/ApoA-I Ratio is Associated With Faster Hemodynamic Progression of Aortic Stenosis: Results From the PROGRESSA (Metabolic Determinants of the Progression of Aortic Stenosis) Study. J Am Heart Assoc. 2018 Feb 10;7(4):e007980. doi: 10.1161/JAHA.117.007980.

  PMID: 29440006 BACKGROUND

• Capoulade R, Larose E, Mathieu P, Clavel MA, Dahou A, Arsenault M, Bedard E, Larue-Grondin S, Le Ven F, Dumesnil JG, Despres JP, Pibarot P. Visceral adiposity and left ventricular mass and function in patients with aortic stenosis: the PROGRESSA study. Can J Cardiol. 2014 Sep;30(9):1080-7. doi: 10.1016/j.cjca.2014.02.007. Epub 2014 Feb 19.

  PMID: 24975192 BACKGROUND

• Capoulade R, Mahmut A, Tastet L, Arsenault M, Bedard E, Dumesnil JG, Despres JP, Larose E, Arsenault BJ, Bosse Y, Mathieu P, Pibarot P. Impact of plasma Lp-PLA2 activity on the progression of aortic stenosis: the PROGRESSA study. JACC Cardiovasc Imaging. 2015 Jan;8(1):26-33. doi: 10.1016/j.jcmg.2014.09.016. Epub 2014 Nov 1.

  PMID: 25499129 BACKGROUND

• Carter S, Capoulade R, Arsenault M, Bedard E, Dumesnil JG, Mathieu P, Pibarot P, Picard F. Relationship Between Insulin-Like Growth Factor Binding Protein-2 and Left Ventricular Stroke Volume in Patients With Aortic Stenosis. Can J Cardiol. 2015 Dec;31(12):1447-54. doi: 10.1016/j.cjca.2015.04.024. Epub 2015 Apr 30.

  PMID: 26243351 BACKGROUND

• Tastet L, Capoulade R, Clavel MA, Larose E, Shen M, Dahou A, Arsenault M, Mathieu P, Bedard E, Dumesnil JG, Tremblay A, Bosse Y, Despres JP, Pibarot P. Systolic hypertension and progression of aortic valve calcification in patients with aortic stenosis: results from the PROGRESSA study. Eur Heart J Cardiovasc Imaging. 2017 Jan;18(1):70-78. doi: 10.1093/ehjci/jew013. Epub 2016 Feb 18.

  PMID: 26896413 BACKGROUND

• Shen M, Tastet L, Capoulade R, Larose E, Bedard E, Arsenault M, Chetaille P, Dumesnil JG, Mathieu P, Clavel MA, Pibarot P. Effect of age and aortic valve anatomy on calcification and haemodynamic severity of aortic stenosis. Heart. 2017 Jan 1;103(1):32-39. doi: 10.1136/heartjnl-2016-309665. Epub 2016 Aug 8.

  PMID: 27504001 BACKGROUND

• Cote N, Mahmut A, Bosse Y, Couture C, Page S, Trahan S, Boulanger MC, Fournier D, Pibarot P, Mathieu P. Inflammation is associated with the remodeling of calcific aortic valve disease. Inflammation. 2013 Jun;36(3):573-81. doi: 10.1007/s10753-012-9579-6.

  PMID: 23225202 BACKGROUND

• El Husseini D, Boulanger MC, Fournier D, Mahmut A, Bosse Y, Pibarot P, Mathieu P. High expression of the Pi-transporter SLC20A1/Pit1 in calcific aortic valve disease promotes mineralization through regulation of Akt-1. PLoS One. 2013;8(1):e53393. doi: 10.1371/journal.pone.0053393. Epub 2013 Jan 4.

  PMID: 23308213 BACKGROUND

• Mahmut A, Boulanger MC, Fournier D, Couture C, Trahan S, Page S, Arsenault B, Despres JP, Pibarot P, Mathieu P. Lipoprotein lipase in aortic valve stenosis is associated with lipid retention and remodelling. Eur J Clin Invest. 2013 Jun;43(6):570-8. doi: 10.1111/eci.12081. Epub 2013 Apr 1.

  PMID: 23550604 BACKGROUND

• Ducharme V, Guauque-Olarte S, Gaudreault N, Pibarot P, Mathieu P, Bosse Y. NOTCH1 genetic variants in patients with tricuspid calcific aortic valve stenosis. J Heart Valve Dis. 2013 Mar;22(2):142-9.

  PMID: 23798201 BACKGROUND

• Cote N, Mahmut A, Fournier D, Boulanger MC, Couture C, Despres JP, Trahan S, Bosse Y, Page S, Pibarot P, Mathieu P. Angiotensin receptor blockers are associated with reduced fibrosis and interleukin-6 expression in calcific aortic valve disease. Pathobiology. 2014;81(1):15-24. doi: 10.1159/000350896. Epub 2013 Aug 21.

  PMID: 23969418 BACKGROUND

• Garcia J, Capoulade R, Le Ven F, Gaillard E, Kadem L, Pibarot P, Larose E. Discrepancies between cardiovascular magnetic resonance and Doppler echocardiography in the measurement of transvalvular gradient in aortic stenosis: the effect of flow vorticity. J Cardiovasc Magn Reson. 2013 Sep 20;15(1):84. doi: 10.1186/1532-429X-15-84.

  PMID: 24053194 BACKGROUND

• Capoulade R, Clavel MA, Mathieu P, Cote N, Dumesnil JG, Arsenault M, Bedard E, Pibarot P. Impact of hypertension and renin-angiotensin system inhibitors in aortic stenosis. Eur J Clin Invest. 2013 Dec;43(12):1262-72. doi: 10.1111/eci.12169. Epub 2013 Oct 7.

  PMID: 24117162 BACKGROUND

• Mahmut A, Boulanger MC, El Husseini D, Fournier D, Bouchareb R, Despres JP, Pibarot P, Bosse Y, Mathieu P. Elevated expression of lipoprotein-associated phospholipase A2 in calcific aortic valve disease: implications for valve mineralization. J Am Coll Cardiol. 2014 Feb 11;63(5):460-9. doi: 10.1016/j.jacc.2013.05.105. Epub 2013 Oct 23.

  PMID: 24161325 BACKGROUND

• Mahmut A, Mahjoub H, Boulanger MC, Fournier D, Despres JP, Pibarot P, Mathieu P. Lp-PLA2 is associated with structural valve degeneration of bioprostheses. Eur J Clin Invest. 2014 Feb;44(2):136-45. doi: 10.1111/eci.12199. Epub 2013 Nov 28.

  PMID: 24328921 BACKGROUND

• Bouchareb R, Boulanger MC, Fournier D, Pibarot P, Messaddeq Y, Mathieu P. Mechanical strain induces the production of spheroid mineralized microparticles in the aortic valve through a RhoA/ROCK-dependent mechanism. J Mol Cell Cardiol. 2014 Feb;67:49-59. doi: 10.1016/j.yjmcc.2013.12.009. Epub 2013 Dec 22.

  PMID: 24368096 BACKGROUND

• El Husseini D, Boulanger MC, Mahmut A, Bouchareb R, Laflamme MH, Fournier D, Pibarot P, Bosse Y, Mathieu P. P2Y2 receptor represses IL-6 expression by valve interstitial cells through Akt: implication for calcific aortic valve disease. J Mol Cell Cardiol. 2014 Jul;72:146-56. doi: 10.1016/j.yjmcc.2014.02.014. Epub 2014 Mar 11.

  PMID: 24631773 BACKGROUND

• Capoulade R, Magne J, Dulgheru R, Hachicha Z, Dumesnil JG, O'Connor K, Arsenault M, Bergeron S, Pierard LA, Lancellotti P, Pibarot P. Prognostic value of plasma B-type natriuretic peptide levels after exercise in patients with severe asymptomatic aortic stenosis. Heart. 2014 Oct;100(20):1606-12. doi: 10.1136/heartjnl-2014-305729.

  PMID: 24993604 BACKGROUND

• Capoulade R, Cote N, Mathieu P, Chan KL, Clavel MA, Dumesnil JG, Teo KK, Tam JW, Fournier D, Despres JP, Pibarot P; ASTRONOMER Investigators. Circulating levels of matrix gla protein and progression of aortic stenosis: a substudy of the Aortic Stenosis Progression Observation: Measuring Effects of rosuvastatin (ASTRONOMER) trial. Can J Cardiol. 2014 Sep;30(9):1088-95. doi: 10.1016/j.cjca.2014.03.025. Epub 2014 Mar 24.

  PMID: 25015689 BACKGROUND

• Potus F, Ruffenach G, Dahou A, Thebault C, Breuils-Bonnet S, Tremblay E, Nadeau V, Paradis R, Graydon C, Wong R, Johnson I, Paulin R, Lajoie AC, Perron J, Charbonneau E, Joubert P, Pibarot P, Michelakis ED, Provencher S, Bonnet S. Downregulation of MicroRNA-126 Contributes to the Failing Right Ventricle in Pulmonary Arterial Hypertension. Circulation. 2015 Sep 8;132(10):932-43. doi: 10.1161/CIRCULATIONAHA.115.016382. Epub 2015 Jul 10.

  PMID: 26162916 BACKGROUND

• Bouchareb R, Mahmut A, Nsaibia MJ, Boulanger MC, Dahou A, Lepine JL, Laflamme MH, Hadji F, Couture C, Trahan S, Page S, Bosse Y, Pibarot P, Scipione CA, Romagnuolo R, Koschinsky ML, Arsenault BJ, Marette A, Mathieu P. Autotaxin Derived From Lipoprotein(a) and Valve Interstitial Cells Promotes Inflammation and Mineralization of the Aortic Valve. Circulation. 2015 Aug 25;132(8):677-90. doi: 10.1161/CIRCULATIONAHA.115.016757. Epub 2015 Jul 29.

  PMID: 26224810 BACKGROUND

• Capoulade R, Chan KL, Yeang C, Mathieu P, Bosse Y, Dumesnil JG, Tam JW, Teo KK, Mahmut A, Yang X, Witztum JL, Arsenault BJ, Despres JP, Pibarot P, Tsimikas S. Oxidized Phospholipids, Lipoprotein(a), and Progression of Calcific Aortic Valve Stenosis. J Am Coll Cardiol. 2015 Sep 15;66(11):1236-1246. doi: 10.1016/j.jacc.2015.07.020.

  PMID: 26361154 BACKGROUND

• Guauque-Olarte S, Messika-Zeitoun D, Droit A, Lamontagne M, Tremblay-Marchand J, Lavoie-Charland E, Gaudreault N, Arsenault BJ, Dube MP, Tardif JC, Body SC, Seidman JG, Boileau C, Mathieu P, Pibarot P, Bosse Y. Calcium Signaling Pathway Genes RUNX2 and CACNA1C Are Associated With Calcific Aortic Valve Disease. Circ Cardiovasc Genet. 2015 Dec;8(6):812-22. doi: 10.1161/CIRCGENETICS.115.001145. Epub 2015 Nov 9.

  PMID: 26553695 BACKGROUND

• Dargis N, Lamontagne M, Gaudreault N, Sbarra L, Henry C, Pibarot P, Mathieu P, Bosse Y. Identification of Gender-Specific Genetic Variants in Patients With Bicuspid Aortic Valve. Am J Cardiol. 2016 Feb 1;117(3):420-6. doi: 10.1016/j.amjcard.2015.10.058. Epub 2015 Nov 19.

  PMID: 26708639 BACKGROUND

• Mahmut A, Mahjoub H, Boulanger MC, Dahou A, Bouchareb R, Capoulade R, Arsenault BJ, Larose E, Bosse Y, Pibarot P, Mathieu P. Circulating Lp-PLA2 is associated with high valvuloarterial impedance and low arterial compliance in patients with aortic valve bioprostheses. Clin Chim Acta. 2016 Apr 1;455:20-5. doi: 10.1016/j.cca.2016.01.014. Epub 2016 Jan 18.

  PMID: 26797670 BACKGROUND

• Capoulade R, Le Ven F, Clavel MA, Dumesnil JG, Dahou A, Thebault C, Arsenault M, O'Connor K, Bedard E, Beaudoin J, Senechal M, Bernier M, Pibarot P. Echocardiographic predictors of outcomes in adults with aortic stenosis. Heart. 2016 Jun 15;102(12):934-42. doi: 10.1136/heartjnl-2015-308742. Epub 2016 Apr 5.

  PMID: 27048774 BACKGROUND

• Hadji F, Boulanger MC, Guay SP, Gaudreault N, Amellah S, Mkannez G, Bouchareb R, Marchand JT, Nsaibia MJ, Guauque-Olarte S, Pibarot P, Bouchard L, Bosse Y, Mathieu P. Altered DNA Methylation of Long Noncoding RNA H19 in Calcific Aortic Valve Disease Promotes Mineralization by Silencing NOTCH1. Circulation. 2016 Dec 6;134(23):1848-1862. doi: 10.1161/CIRCULATIONAHA.116.023116. Epub 2016 Oct 27.

  PMID: 27789555 BACKGROUND

• Capoulade R, Clavel MA, Le Ven F, Dahou A, Thebault C, Tastet L, Shen M, Arsenault M, Bedard E, Beaudoin J, O'Connor K, Bernier M, Dumesnil JG, Pibarot P. Impact of left ventricular remodelling patterns on outcomes in patients with aortic stenosis. Eur Heart J Cardiovasc Imaging. 2017 Dec 1;18(12):1378-1387. doi: 10.1093/ehjci/jew288.

  PMID: 28064154 BACKGROUND

• Tastet L, Enriquez-Sarano M, Capoulade R, Malouf J, Araoz PA, Shen M, Michelena HI, Larose E, Arsenault M, Bedard E, Pibarot P, Clavel MA. Impact of Aortic Valve Calcification and Sex on Hemodynamic Progression and Clinical Outcomes in AS. J Am Coll Cardiol. 2017 Apr 25;69(16):2096-2098. doi: 10.1016/j.jacc.2017.02.037. No abstract available.

  PMID: 28427584 BACKGROUND

• Nsaibia MJ, Boulanger MC, Bouchareb R, Mkannez G, Le Quang K, Hadji F, Argaud D, Dahou A, Bosse Y, Koschinsky ML, Pibarot P, Arsenault BJ, Marette A, Mathieu P. OxLDL-derived lysophosphatidic acid promotes the progression of aortic valve stenosis through a LPAR1-RhoA-NF-kappaB pathway. Cardiovasc Res. 2017 Sep 1;113(11):1351-1363. doi: 10.1093/cvr/cvx089.

  PMID: 28472283 BACKGROUND

• Shen M, Tastet L, Bergler-Klein J, Pibarot P, Clavel MA. Blood, tissue and imaging biomarkers in calcific aortic valve stenosis: past, present and future. Curr Opin Cardiol. 2018 Mar;33(2):125-133. doi: 10.1097/HCO.0000000000000487.

  PMID: 29194051 BACKGROUND

• Theriault S, Gaudreault N, Lamontagne M, Rosa M, Boulanger MC, Messika-Zeitoun D, Clavel MA, Capoulade R, Dagenais F, Pibarot P, Mathieu P, Bosse Y. A transcriptome-wide association study identifies PALMD as a susceptibility gene for calcific aortic valve stenosis. Nat Commun. 2018 Mar 7;9(1):988. doi: 10.1038/s41467-018-03260-6.

  PMID: 29511167 BACKGROUND

• Shen M, Tastet L, Capoulade R, Bedard E, Arsenault M, Clavel MA, Pibarot P. Determinants of Aortic Stenosis Progression in Bicuspid and Tricuspid Aortic Valves. CJC Pediatr Congenit Heart Dis. 2022 Jul 7;1(4):184-192. doi: 10.1016/j.cjcpc.2022.06.004. eCollection 2022 Aug.

  PMID: 37969929 DERIVED

• Shen M, Tastet L, Capoulade R, Arsenault M, Bedard E, Clavel MA, Pibarot P. Effect of bicuspid aortic valve phenotype on progression of aortic stenosis. Eur Heart J Cardiovasc Imaging. 2020 Jul 1;21(7):727-734. doi: 10.1093/ehjci/jeaa068.

  PMID: 32386199 DERIVED

• Everett RJ, Tastet L, Clavel MA, Chin CWL, Capoulade R, Vassiliou VS, Kwiecinski J, Gomez M, van Beek EJR, White AC, Prasad SK, Larose E, Tuck C, Semple S, Newby DE, Pibarot P, Dweck MR. Progression of Hypertrophy and Myocardial Fibrosis in Aortic Stenosis: A Multicenter Cardiac Magnetic Resonance Study. Circ Cardiovasc Imaging. 2018 Jun;11(6):e007451. doi: 10.1161/CIRCIMAGING.117.007451.

  PMID: 29914867 DERIVED

• Pawade T, Clavel MA, Tribouilloy C, Dreyfus J, Mathieu T, Tastet L, Renard C, Gun M, Jenkins WSA, Macron L, Sechrist JW, Lacomis JM, Nguyen V, Galian Gay L, Cuellar Calabria H, Ntalas I, Cartlidge TRG, Prendergast B, Rajani R, Evangelista A, Cavalcante JL, Newby DE, Pibarot P, Messika Zeitoun D, Dweck MR. Computed Tomography Aortic Valve Calcium Scoring in Patients With Aortic Stenosis. Circ Cardiovasc Imaging. 2018 Mar;11(3):e007146. doi: 10.1161/CIRCIMAGING.117.007146.

  PMID: 29555836 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Fasting blood sample (serum, lithium-heparin, EDTA) and white cells - Tissue (explanted aortic valves)

MeSH Terms

Conditions

Aortic Valve Stenosis; Obesity, Abdominal; Metabolic Syndrome; Insulin Resistance

Interventions

Echocardiography, Doppler; Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Aortic Valve Disease; Heart Valve Diseases; Heart Diseases; Cardiovascular Diseases; Ventricular Outflow Obstruction; Obesity; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases

Intervention Hierarchy (Ancestors)

Echocardiography; Cardiac Imaging Techniques; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Ultrasonography; Ultrasonography, Doppler; Heart Function Tests; Diagnostic Techniques, Cardiovascular; Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques

Study Officials

• Philippe Pibarot, PhD, DVM

  Institut universitaire de cardiologie et de pneumologie de Québec, University Laval

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Philippe Pibarot, PhD, DVM

CONTACT

418-656-8711; Philippe.Pibarot@med.ulaval.ca

Romain Capoulade, MSc

CONTACT

418-656-8711; Romain.Capoulade@criucpq.ulaval.ca

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Doctor

Study Record Dates

• First Submitted: August 24, 2012
• First Posted: September 6, 2012
• Study Start: April 1, 2005
• Primary Completion: January 1, 2024
• Study Completion: January 1, 2024
• Last Updated: September 21, 2021

Record last verified: 2021-09

Locations

CA (1)