[en] Valvular heart disease (VHD) is a common condition that poses several challenges from the standpoints of diagnosis and therapeutic management. While several studies have explored the role of blood biomarkers in assessing the severity and risk of progression of VHD, as well as in evaluating related cardiac damage and predicting the occurrence of adverse events, blood biomarkers are generally not considered criteria to trigger valve intervention in the latest European and American guidelines for VHD management. This review article provides an up-to-date overview of the utility of blood biomarkers to (i) assess the presence, severity, and progression of left-sided VHD; (ii) establish the presence and extent of cardiovascular damage; (iii) predict clinical outcomes before and after valve interventions; and (iv) identify patients at risk for early structural valve deterioration, valve thrombosis, and paravalvular leak.
Disciplines :
Cardiovascular & respiratory systems
Author, co-author :
Coisne, Augustin ; Univ. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U1011-EGID, Bd Pr Jules Leclercq, 59000 Lille, France ; Cardiovascular Research Foundation, New York City, NY 10019, USA
Lancellotti, Patrizio ; Université de Liège - ULiège > Département des sciences cliniques > Cardiologie - Pathologie spéciale et réhabilitation
Côté, Nancy; Institut Universitaire de Cardiologie et de Pneumologie de Québec (Quebec Heart and Lung Institute), Université Laval, Quebec City, Quebec, Canada
Ternacle, Julien ; Service Médico-Chirurgical: Valvulopathies-Chirurgie Cardiaque-Cardiologie Interventionnelle Structurelle, Centre Hospitalier Universitaire Bordeaux, Bordeaux, France
Hecht, Sébastien; Institut Universitaire de Cardiologie et de Pneumologie de Québec (Quebec Heart and Lung Institute), Université Laval, Quebec City, Quebec, Canada
Grapsa, Julia ; Guy's and St Thomas' NHS Trust Hospitals, London, UK
Hahn, Rebecca T; Columbia University Medical Center/NY Presbyterian Hospital, New York City, NY 10032, USA
Clavel, Marie-Annick ; Institut Universitaire de Cardiologie et de Pneumologie de Québec (Quebec Heart and Lung Institute), Université Laval, Quebec City, Quebec, Canada
Vannan, Mani A; Marcus Heart Valve Center, Piedmont Heart Institute, Atlanta, GA, USA
Lindman, Brian ; Vanderbilt University, Nashville, TN, USA
Garbi, Madalina; Royal Papworth Hospital, Cambridge University Health Partners, Cambridge Biomedical Campus, Cambridge, UK
Donal, Erwan ; Cardiology Department, CHU de Rennes, Rennes, France
Scotti, Andrea ; Montefiore-Einstein Center for Heart and Vascular Care, Montefiore Medical Center, Albert Einstein College, Bronx, NY 10467, USA
Ludwig, Sebastian ; Cardiovascular Research Foundation, New York City, NY 10019, USA ; Department of Cardiology, University Heart & Vascular Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Postolache, Adriana ; Université de Liège - ULiège > Département des sciences cliniques ; CHU UCL Namur- Site Godinne, Namur, Belgium
Myers, Patrick; Hôpital de LaTour, Meyrin, Switzerland
Dweck, Marc R; BHF Centre of Cardiovascular Science, The University of Edinburgh, Edinburgh, UK
Pibarot, Philippe ; Institut Universitaire de Cardiologie et de Pneumologie de Québec (Quebec Heart and Lung Institute), Université Laval, Quebec City, Quebec, Canada
A.C. is the proctor for Abbott Vascular and received speaker fees for Abbot Vascular, Edwards Lifescience, GE Healthcare, BMS, MSD, Pfizer. J.T. is a consultant for Abbott Structural, Edwards Lifesciences, General Electric, Philips and Pi-Cardia. R.T.H. reports speaker fees from Abbott Structural, Baylis Medical, Edwards Lifesciences, and Philips Healthcare; she has institutional consulting contracts for which she receives no direct compensation with Abbott Structural, Anteris, Boston Scientific, Edwards Lifesciences, Medtronic, Novartis, and Philips Healthcare; she is the Chief Scientific Officer for the Echocardiography Core Laboratory at the Cardiovascular Research Foundation for multiple industry-sponsored valve trials, for which she receives no direct industry compensation. M.-A.C. has received funding from Edwards Lifesciences, Medtronic, Pi-Cardia, Novartis and Rednvia for research studies and CT core laboratory analyses, for which she received no personal compensation. B.L. is a consultant for Edwards Lifesciences, Medtronic, Anteris, and Astra Zeneca, received investigator-initiated research funding from Edwards Lifesciences, and is PI of the biobanks for the EARLY TAVR and PROGRESS trials. P.P. has received funding from Edwards Lifesciences, Medtronic, Pi-Cardia, Cardiac Success, and Novartis for echocardiography core laboratory analyses and research studies in the field of valvular heart disease, for which he received no personal compensation. P.P. has received lecture fees from Edwards Lifesciences and Medtronic. The remaining authors have no conflicts of interest to declare.
Vahanian A, Beyersdorf F, Praz F, Milojevic M, Baldus S, Bauersachs J, et al. 2021 ESC/EACTS guidelines for the management of valvular heart disease. Eur Heart J 2022; 43: 561-632. 10.1093/eurheartj/ehab395.
Writing Committee Members; Otto CM, Nishimura RA, Bonow RO, Carabello BA, Erwin JP III, et al. 2020 ACC/AHA guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol 2021; 77: e25-197. 10.1016/j.jacc.2020.11.018
Coisne A, Lancellotti P, Habib G, Garbi M, Dahl JS, Barbanti M, et al. ACC/AHA and ESC/EACTS guidelines for the management of valvular heart diseases: JACC guideline comparison. J Am Coll Cardiol 2023; 82: 721-34. 10.1016/j.jacc.2023.05.061
Clavel MA, Malouf J, Michelena HI, Suri RM, Jaffe AS, Mahoney DW, et al. B-type natriuretic peptide clinical activation in aortic stenosis: impact on long-term survival. J Am Coll Cardiol 2014; 63: 2016-25. 10.1016/j.jacc.2014.02.581
Bergler-Klein J, Klaar U, Heger M, Rosenhek R, Mundigler G, Gabriel H, et al. Natriuretic peptides predict symptom-free survival and postoperative outcome in severe aortic stenosis. Circulation 2004; 109: 2302-8. 10.1161/01.CIR.0000126825.50903.18
Chin CWL, Shah ASV, McAllister DA, Joanna Cowell S, Alam S, Langrish JP, et al. High-sensitivity troponin I concentrations are a marker of an advanced hypertrophic response and adverse outcomes in patients with aortic stenosis. Eur Heart J 2014; 35: 2312-21. 10.1093/eurheartj/ehu189
Lindman BR, Breyley JG, Schilling JD, Vatterott AM, Zajarias A, Maniar HS, et al. Prognostic utility of novel biomarkers of cardiovascular stress in patients with aortic stenosis undergoing valve replacement. Heart 2015; 101: 1382-8. 10.1136/heartjnl-2015-307742
Bach DS, Cimino N, Deeb GM. Unoperated patients with severe aortic stenosis. J Am Coll Cardiol 2007; 50: 2018-9. 10.1016/j.jacc.2007.08.011
Eugène M, Duchnowski P, Prendergast B, Wendler O, Laroche C, Monin J-L, et al. Contemporary management of severe symptomatic aortic stenosis. J Am Coll Cardiol 2021; 78: 2131-43. 10.1016/j.jacc.2021.09.864
Brennan JM, Lowenstern A, Sheridan P, Boero IJ, Thourani VH, Vemulapalli S, et al. Association between patient survival and clinician variability in treatment rates for aortic valve stenosis. J Am Heart Assoc 2021; 10: e020490. 10.1161/JAHA.120.020490
Flannery L, Etiwy M, Camacho A, Liu R, Patel N, Tavil-Shatelyan A, et al. Patient- and process-related contributors to the underuse of aortic valve replacement and subsequent mortality in ambulatory patients with severe aortic stenosis. J Am Heart Assoc 2022; 11: e025065. 10.1161/JAHA.121.025065
Li SX, Patel NK, Flannery LD, Selberg A, Kandanelly RR, Morrison FJ, et al. Trends in utilization of aortic valve replacement for severe aortic stenosis. J Am Coll Cardiol 2022; 79: 864-77. 10.1016/j.jacc.2021.11.060
Dziadzko V, Clavel MA, Dziadzko M, Medina-Inojosa JR, Michelena H, Maalouf J, et al. Outcome and undertreatment of mitral regurgitation: a community cohort study. Lancet 2018; 391: 960-9. 10.1016/S0140-6736(18)30473-2
Kamstrup PR, Tybjærg-Hansen A, Nordestgaard BG. Elevated lipoprotein(a) and risk of aortic valve stenosis in the general population. J Am Coll Cardiol 2014; 63: 470-7. 10.1016/j.jacc.2013.09.038
Mahabadi AA, Kahlert P, Kahlert HA, Dykun I, Balcer B, Forsting M, et al. Comparison of lipoprotein(a)-levels in patients ≥70 years of age with versus without aortic valve stenosis. Am J Cardiol 2018; 122: 645-9. 10.1016/j.amjcard.2018.04.046
Girard A, Gaillard E, Puri R, Capoulade R, Chan KL, Paulin A, et al. Impact of C-reactive protein levels on lipoprotein(a)-associated aortic stenosis incidence and progression. Eur Heart J Open 2023; 3: oead032. 10.1093/ehjopen/oead032
Nazarzadeh M, Pinho-Gomes AC, Bidel Z, Dehghan A, Canoy D, Hassaine A, et al. Plasma lipids and risk of aortic valve stenosis: a Mendelian randomization study. Eur Heart J 2020; 41: 3913-20. 10.1093/eurheartj/ehaa070
Stewart BF, Siscovick D, Lind BK, Gardin JM, Gottdiener JS, Smith VE, et al. Clinical factors associated with calcific aortic valve disease. Cardiovascular Health Study. J Am Coll Cardiol 1997; 29: 630-4. 10.1016/S0735-1097(96)00563-3
Chui MC, Newby DE, Panarelli M, Bloomfield P, Boon NA. Association between calcific aortic stenosis and hypercholesterolemia: is there a need for a randomized controlled trial of cholesterol-lowering therapy? Clin Cardiol 2001; 24: 52-5. 10.1002/clc.4960240109
Poggio P, Songia P, Cavallotti L, Barbieri SS, Zanotti I, Arsenault BJ, et al. PCSK9 involvement in aortic valve calcification. J Am Coll Cardiol 2018; 72: 3225-7. 10.1016/j.jacc.2018.09.063
Perrot N, Valerio V, Moschetta D, Boekholdt SM, Dina C, Chen HY, et al. Genetic and in vitro inhibition of PCSK9 and calcific aortic valve stenosis. JACC Basic Transl Sci 2020; 5: 649-61. 10.1016/j.jacbts.2020.05.004
Bergmark BA, O'Donoghue ML, Murphy SA, Kuder JF, Ezhov MV, Ceška R, et al. An exploratory analysis of proprotein convertase subtilisin/kexin type 9 inhibition and aortic stenosis in the FOURIER trial. JAMA Cardiol 2020; 5: 709-13. 10.1001/jamacardio.2020.0728
Iwahashi N, Nakatani S, Umemura S, Kimura K, Kitakaze M. Usefulness of plasma B-type natriuretic peptide in the assessment of disease severity and prediction of outcome after aortic valve replacement in patients with severe aortic stenosis. J Am Soc Echocardiogr 2011; 24: 984-91. 10.1016/j.echo.2011.03.012
Gerber IL, Stewart RAH, Legget ME, West TM, French RL, Sutton TM, et al. Increased plasma natriuretic peptide levels reflect symptom onset in aortic stenosis. Circulation 2003; 107: 1884-90. 10.1161/01.CIR.0000060533.79248.0C
Lancellotti P, Magne J, Donal E, Davin L, O'Connor K, Rosca M, et al. Clinical outcome in asymptomatic severe aortic stenosis: insights from the new proposed aortic stenosis grading classification. J Am Coll Cardiol 2012; 59: 235-43. 10.1016/j.jacc.2011.08.072
Henri C, Dulgheru R, Magne J, Caballero L, Laaraibi S, Davin L, et al. Impact of serial B-type natriuretic peptide changes for predicting outcome in asymptomatic patients with aortic stenosis. Can J Cardiol 2016; 32: 183-9. 10.1016/j.cjca.2015.06.007
Gerber IL, Legget ME, West TM, Richards AM, Stewart RAH. Usefulness of serial measurement of N-terminal pro-brain natriuretic peptide plasma levels in asymptomatic patients with aortic stenosis to predict symptomatic deterioration. Am J Cardiol 2005; 95: 898-901. 10.1016/j.amjcard.2004.11.053
Holmgren A, Ljungberg J, Hultdin J, Johansson B, Bergdahl IA, Näslund U, et al. Troponin T but not C reactive protein is associated with future surgery for aortic stenosis: a population-based nested case-referent study. Open Heart 2020; 7: e001325. 10.1136/openhrt-2020-001325
Røsjø H, Andreassen J, Edvardsen T, Omland T. Prognostic usefulness of circulating high-sensitivity troponin T in aortic stenosis and relation to echocardiographic indexes of cardiac function and anatomy. Am J Cardiol 2011; 108: 88-91. 10.1016/j.amjcard.2011.02.346
Lancellotti P, Dulgheru R, Magne J, Henri C, Servais L, Bouznad N, et al. Elevated plasma soluble ST2 is associated with heart failure symptoms and outcome in aortic stenosis. PLoS One 2015; 10: e0138940. 10.1371/journal.pone.0138940
van Driel BO, Schuldt M, Algül S, Levin E, Güclü A, Germans T, et al. Metabolomics in severe aortic stenosis reveals intermediates of nitric oxide synthesis as most distinctive markers. Int J Mol Sci 2021; 22: 3569. 10.3390/ijms22073569
Bengel P, Elkenani M, Beuthner BE, Pietzner M, Mohamed BA, Pollok-Kopp B, et al. Metabolomic profiling in patients with different hemodynamic subtypes of severe aortic valve stenosis. Biomolecules 2023; 13: 95. 10.3390/biom13010095
Surendran A, Edel A, Chandran M, Bogaert P, Hassan-Tash P, Kumar Asokan A, et al. Metabolomic signature of human aortic valve stenosis. JACC Basic Transl Sci 2020; 5: 1163-77. 10.1016/j.jacbts.2020.10.001
Villar AV, García R, Merino D, Llano M, Cobo M, Montalvo C, et al. Myocardial and circulating levels of microRNA-21 reflect left ventricular fibrosis in aortic stenosis patients. Int J Cardiol 2013; 167: 2875-81. 10.1016/j.ijcard.2012.07.021
Yang F, Liu S, Gu Y, Yan Y, Ding X, Zou L, et al. MicroRNA-22 promoted osteogenic differentiation of valvular interstitial cells by inhibiting CAB39 expression during aortic valve calcification. Cell Mol Life Sci 2022; 79: 146. 10.1007/s00018-022-04177-6
Song R, Zhai Y, Ao L, Fullerton DA, Meng X. MicroRNA-204 deficiency in human aortic valves elevates valvular osteogenic activity. Int J Mol Sci 2019; 21: 76. 10.3390/ijms21010076
Røsjø H, Dahl MB, Bye A, Andreassen J, Jørgensen M, Wisløff U, et al. Prognostic value of circulating microRNA-210 levels in patients with moderate to severe aortic stenosis. PLoS One 2014; 9: e91812. 10.1371/journal.pone.0091812
Chen Z, Li C, Xu Y, Li Y, Yang H, Rao L. Circulating level of miR-378 predicts left ventricular hypertrophy in patients with aortic stenosis. PLoS One 2014; 9: e105702. 10.1371/journal.pone.0105702
Imai K, Okura H, Kume T, Yamada R, Miyamoto Y, Kawamoto T, et al. C-reactive protein predicts severity, progression, and prognosis of asymptomatic aortic valve stenosis. Am Heart J 2008; 156: 713-8. 10.1016/j.ahj.2008.04.011
Shelbaya K, Arthur V, Yang Y, Dorbala P, Buckley L, Claggett B, et al. Large-scale proteomics identifies novel biomarkers and circulating risk factors for aortic stenosis. J Am Coll Cardiol 2024; 83: 577-91. 10.1016/j.jacc.2023.11.021
Zheng KH, Tsimikas S, Pawade T, Kroon J, Jenkins WSA, Doris MK, et al. Lipoprotein(a) and oxidized phospholipids promote valve calcification in patients with aortic stenosis. J Am Coll Cardiol 2019; 73: 2150-62. 10.1016/j.jacc.2019.01.070
Cowell SJ, Newby DE, Prescott RJ, Bloomfield P, Reid J, Northridge DB, et al. A randomized trial of intensive lipid-lowering therapy in calcific aortic stenosis. N Engl J Med 2005; 352: 2389-97. 10.1056/NEJMoa043876
Capoulade R, Torzewski M, Mayr M, Chan KL, Mathieu P, Bossé Y, et al. ApoCIII-Lp(a) complexes in conjunction with Lp(a)-OxPL predict rapid progression of aortic stenosis. Heart 2020; 106: 738-45. 10.1136/heartjnl-2019-315840
Kronenberg F, Mora S, Stroes ESG, Ference BA, Arsenault BJ, Berglund L, et al. Lipoprotein(a) in atherosclerotic cardiovascular disease and aortic stenosis: a European Atherosclerosis Society consensus statement. Eur Heart J 2022; 43: 3925-46. 10.1093/eurheartj/ehac361
Sánchez PL, Santos JL, Kaski JC, Cruz I, Arribas A, Villacorta E, et al. Relation of circulating C-reactive protein to progression of aortic valve stenosis. Am J Cardiol 2006; 97: 90-3. 10.1016/j.amjcard.2005.07.113
Capoulade R, Mahmut A, Tastet L, Arsenault M, Bédard É, Dumesnil JG, et al. Impact of plasma Lp-PLA2 activity on the progression of aortic stenosis: the PROGRESSA study. JACC Cardiovasc Imaging 2015; 8: 26-33. 10.1016/j.jcmg.2014.09.016
Mohty D, Pibarot P, Després JP, Côté C, Arsenault B, Cartier A, et al. Association between plasma LDL particle size, valvular accumulation of oxidized LDL, and inflammation in patients with aortic stenosis. Arterioscler Thromb Vasc Biol 2008; 28: 187-93. 10.1161/ATVBAHA.107.154989
Côté N, Couture C, Pibarot P, Després JP, Mathieu P. Angiotensin receptor blockers are associated with a lower remodelling score of stenotic aortic valves. Eur J Clin Invest 2011; 41: 1172-9. 10.1111/j.1365-2362.2011.02522.x
Capoulade R, Clavel MA, Mathieu P, Côté N, Dumesnil JG, Arsenault M, et al. Impact of hypertension and renin-angiotensin system inhibitors in aortic stenosis. Eur J Clin Invest 2013; 43: 1262-72. 10.1111/eci.12169
Lee S, Lee S-A, Choi B, Kim Y-J, Oh SJ, Choi H-M, et al. Dipeptidyl peptidase-4 inhibition to prevent progression of calcific aortic stenosis. Heart 2020; 106: 1824-31. 10.1136/heartjnl-2020-317024
Mathieu P, Bouchareb R, Boulanger MC. Innate and adaptive immunity in calcific aortic valve disease. J Immunol Res 2015; 2015: 851945. 10.1155/2015/851945
Liu S, Ngo DTM, Chong CR, Amarasekera AT, Procter NEK, Licari G, et al. Suppression of neutrophil superoxide generation by BNP is attenuated in acute heart failure: a case for "BNP resistance". Eur J Heart Fail 2015; 17: 475-83. 10.1002/ejhf.242
Villacorta H, Maisel AS. Soluble ST2 testing: a promising biomarker in the management of heart failure. Arq Bras Cardiol 2016; 106: 145-52. 10.5935/abc.20150151
Broch K, Ueland T, Nymo SH, Kjekshus J, Hulthe J, Muntendam P, et al. Soluble ST2 is associated with adverse outcome in patients with heart failure of ischaemic aetiology. Eur J Heart Fail 2012; 14: 268-77. 10.1093/eurjhf/hfs006
Bayes-Genis A, de Antonio M, Vila J, Peñafiel J, Galán A, Barallat J, et al. Head-to-head comparison of 2 myocardial fibrosis biomarkers for long-term heart failure risk stratification: ST2 versus galectin-3. J Am Coll Cardiol 2014; 63: 158-66. 10.1016/j.jacc.2013.07.087
Arrieta V, Jover E, Navarro A, Martin-Nunez E, Garaikoetxea M, Matilla L, et al. Soluble ST2 levels are related to replacement myocardial fibrosis in severe aortic stenosis. Rev Espanola Cardiol (Engl Ed) 2023; 76: 679-89. 10.1016/j.rec.2022.12.007
Fabiani I, Conte L, Pugliese NR, Calogero E, Barletta V, Di Stefano R, et al. The integrated value of sST2 and global longitudinal strain in the early stratification of patients with severe aortic valve stenosis: a translational imaging approach. Int J Cardiovasc Imaging 2017; 33: 1915-20. 10.1007/s10554-017-1203-2
Elmariah S, McCarthy C, Ibrahim N, Furman D, Mukai R, Magaret C, et al. Multiple biomarker panel to screen for severe aortic stenosis: results from the CASABLANCA study. Open Heart 2018; 5: e000916. 10.1136/openhrt-2018-000916
Vincentelli A, Susen S, Le Tourneau T, Six I, Fabre O, Juthier F, et al. Acquired von Willebrand syndrome in aortic stenosis. N Engl J Med 2003; 349: 343-9. 10.1056/NEJMoa022831
Van Belle E, Rauch A, Vincent F, Robin E, Kibler M, Labreuche J, et al. Von Willebrand factor multimers during transcatheter aortic-valve replacement. N Engl J Med 2016; 375: 335-44. 10.1056/NEJMoa1505643
Van Belle E, Vincent F, Rauch A, Casari C, Jeanpierre E, Loobuyck V, et al. von Willebrand factor and management of heart valve disease: JACC review topic of the week. J Am Coll Cardiol 2019; 73: 1078-88. 10.1016/j.jacc.2018.12.045
Zeller J, Loseff-Silver J, Khoshmanesh K, Baratchi S, Lai A, Nero TL, et al. Shear-sensing by C-reactive protein: linking aortic stenosis and inflammation. Circ Res 2024; 135: 1033-47. 10.1161/CIRCRESAHA.124.324248
Arsenault BJ, Loganath K, Girard A, Botezatu S, Zheng KH, Tzolos E, et al. Lipoprotein(a) and calcific aortic valve stenosis progression: a systematic review and meta-analysis. JAMA Cardiol 2024; 9: 835-42. 10.1001/jamacardio.2024.1882
Mahmut A, Boulanger MC, El Husseini D, Fournier D, Bouchareb R, Després JP, et al. Elevated expression of lipoprotein-associated phospholipase A2 in calcific aortic valve disease: implications for valve mineralization. J Am Coll Cardiol 2014; 63: 460-9. 10.1016/j.jacc.2013.05.105
Côté N, Pibarot P, Pépin A, Fournier D, Audet A, Arsenault B, et al. 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; 145: 444-9. 10.1016/j.ijcard.2009.05.054
Carter-Storch R, Le Nezet E, Ali M, Powers A, Haujir A, Demers K, et al. Angiotensin II receptor blockers are associated with reduced valvular fibrosis in women with aortic stenosis. Can J Cardiol 2024; 40: 1690-9. 10.1016/j.cjca.2024.03.009
Song J-K, Lee S, Kim Y-J, Kim H-K, Ha J-W, Choi E-Y, et al. Effect of evogliptin on the progression of aortic valvular calcification. J Am Coll Cardiol 2024; 84: 1064-75. 10.1016/j.jacc.2024.06.037
Luo G, Ducy P, McKee MD, Pinero GJ, Loyer E, Behringer RR, et al. Spontaneous calcification of arteries and cartilage in mice lacking matrix GLA protein. Nature 1997; 386: 78-81. 10.1038/386078a0
Gragnano F, Crisci M, Bigazzi MC, Bianchi R, Sperlongano S, Natale F, et al. Von Willebrand factor as a novel player in valvular heart disease: from bench to valve replacement. Angiology 2018; 69: 103-12. 10.1177/0003319717708070
Jiang L, Wang J, Li R, Fang Z-M, Zhu X-H, Yi X, et al. Disturbed energy and amino acid metabolism with their diagnostic potential in mitral valve disease revealed by untargeted plasma metabolic profiling. Metabolomics 2019; 15: 57. 10.1007/s11306-019-1518-1
Deroyer C, Magne J, Moonen M, Le Goff C, Dupont L, Hulin A, et al. New biomarkers for primary mitral regurgitation. Clin Proteomics 2015; 12: 25. 10.1186/s12014-015-9097-2
Tan HT, Ling LH, Dolor-Torres MC, Yip JW-L, Richards AM, Chung MCM. Proteomics discovery of biomarkers for mitral regurgitation caused by mitral valve prolapse. J Proteomics 2013; 94: 337-45. 10.1016/j.jprot.2013.10.009
Hojo Y, Kumakura H, Kanai H, Iwasaki T, Ichikawa S, Kurabayashi M. Lipoprotein(a) is a risk factor for aortic and mitral valvular stenosis in peripheral arterial disease. Eur Heart J Cardiovasc Imaging 2016; 17: 492-7. 10.1093/ehjci/jev338
Kaltoft M, Sigvardsen PE, Afzal S, Langsted A, Fuchs A, Kühl JT, et al. Elevated lipoprotein(a) in mitral and aortic valve calcification and disease: the Copenhagen General Population Study. Atherosclerosis 2022; 349: 166-74. 10.1016/j.atherosclerosis.2021.11.029
Garg PK, Guan W, Karger AB, Steffen BT, Budoff M, Tsai MY. Lipoprotein (a) and risk for calcification of the coronary arteries, mitral valve, and thoracic aorta: the Multi-Ethnic Study of Atherosclerosis. J Cardiovasc Comput Tomogr 2021; 15: 154-60. 10.1016/j.jcct.2020.06.002
Detaint D, Messika-Zeitoun D, Avierinos JF, Scott C, Chen H, Burnett JC, et al. B-type natriuretic peptide in organic mitral regurgitation: determinants and impact on outcome. Circulation 2005; 111: 2391-7. 10.1161/01.CIR.0000164269.80908.9D
Magne J, Mahjoub H, Pierard LA, O'Connor K, Pirlet C, Pibarot P, et al. Prognostic importance of brain natriuretic peptide and left ventricular longitudinal function in asymptomatic degenerative mitral regurgitation. Heart 2012; 98: 584-91. 10.1136/heartjnl-2011-301128
Clavel MA, Tribouilloy C, Vanoverschelde JL, Pizarro R, Suri RM, Szymanski C, et al. Association of B-type natriuretic peptide with survival in patients with degenerative mitral regurgitation. J Am Coll Cardiol 2016; 68: 1297-307. 10.1016/j.jacc.2016.06.047
Pizarro R, Bazzino OO, Oberti PF, Falconi M, Achilli F, Arias A, et al. Prospective validation of the prognostic usefulness of brain natriuretic peptide in asymptomatic patients with chronic severe mitral regurgitation. J Am Coll Cardiol 2009; 54: 1099-106. 10.1016/j.jacc.2009.06.013
Klaar U, Gabriel H, Bergler-Klein J, Pernicka E, Heger M, Mascherbauer J, et al. Prognostic value of serial B-type natriuretic peptide measurement in asymptomatic organic mitral regurgitation. Eur J Heart Fail 2011; 13: 163-9. 10.1093/eurjhf/hfq189
Ogata F, Hanatani S, Nakashima N, Yamamoto M, Shirahama Y, Ishii M, et al. Human epididymis protein 4 is a useful predictor of post-operative prognosis in patients with severe aortic stenosis. ESC Heart Fail 2024; 11: 2924-32. 10.1002/ehf2.14845
Chen M-C, Chang T-H, Chang J-P, Huang H-D, Ho W-C, Lin Y-S, et al. Circulating miR-148b-3p and miR-409-3p as biomarkers for heart failure in patients with mitral regurgitation. Int J Cardiol 2016; 222: 148-54. 10.1016/j.ijcard.2016.07.179
Spinka G, Bartko PE, Pavo N, Freitag C, Zlabinger K, Prausmüller S, et al. Secondary mitral regurgitation-insights from microRNA assessment. Eur J Clin Invest 2021; 51: e13381. 10.1111/eci.13381
Duchnowski P, Hryniewiecki T, Kuśmierczyk M, Szymański P. The usefulness of selected biomarkers in aortic regurgitation. Cardiol J 2019; 26: 477-82. 10.5603/CJ.a2018.0108
Pizarro R, Bazzino OO, Oberti PF, Falconi ML, Arias AM, Krauss JG, et al. Prospective validation of the prognostic usefulness of B-type natriuretic peptide in asymptomatic patients with chronic severe aortic regurgitation. J Am Coll Cardiol 2011; 58: 1705-14. 10.1016/j.jacc.2011.07.016
Chen S, Redfors B, O'Neill BP, Clavel MA, Pibarot P, Elmariah S, et al. Low and elevated B-type natriuretic peptide levels are associated with increased mortality in patients with preserved ejection fraction undergoing transcatheter aortic valve replacement: an analysis of the PARTNER II trial and registry. Eur Heart J 2020; 41: 958-69. 10.1093/eurheartj/ehz892
Clavel MA, Messika-Zeitoun D, Pibarot P, Aggarwal SR, Malouf J, Araoz PA, et al. The complex nature of discordant severe calcified aortic valve disease grading: new insights from combined Doppler echocardiographic and computed tomographic study. J Am Coll Cardiol 2013; 62: 2329-38. 10.1016/j.jacc.2013.08.1621
Zhang B, Xu H, Zhang H, Liu Q, Ye Y, Hao J, et al. Prognostic value of N-terminal pro-B-type natriuretic peptide in elderly patients with valvular heart disease. J Am Coll Cardiol 2020; 75: 1659-72. 10.1016/j.jacc.2020.02.031
Redfield MM, Rodeheffer RJ, Jacobsen SJ, Mahoney DW, Bailey KR, Burnett JC. Plasma brain natriuretic peptide concentration: impact of age and gender. J Am Coll Cardiol 2002; 40: 976-82. 10.1016/S0735-1097(02)02059-4
Clerico A, Zaninotto M, Prontera C, Giovannini S, Ndreu R, Franzini M, et al. State of the art of BNP and NT-proBNP immunoassays: the CardioOrmoCheck study. Clin Chim Acta 2012; 414: 112-9. 10.1016/j.cca.2012.07.017
Loganath K, Craig NJ, Everett RJ, Bing R, Tsampasian V, Molek P, et al. Early intervention in patients with asymptomatic severe aortic stenosis and myocardial fibrosis: the EVOLVED randomized clinical trial. JAMA 2025; 333: 213-21. 10.1001/jama.2024.22730
Baldenhofer G, Zhang K, Spethmann S, Laule M, Eilers B, Leonhardt F, et al. Galectin-3 predicts short- and long-term outcome in patients undergoing transcatheter aortic valve implantation (TAVI). Int J Cardiol 2014; 177: 912-7. 10.1016/j.ijcard.2014.10.010
Zhang H-L, Song G-Y, Zhao J, Wang Y-B, Wang M-Y, Xu Y-L, et al. Preprocedural circulating galectin-3 and the risk of mortality after transcatheter aortic valve replacement: a systematic review and meta-analysis. Biosci Rep 2020; 40: BSR20202306. 10.1042/BSR20202306
Cai A, Miyazawa A, Sunderland N, Piper SE, Gibbs TGJ, Wang D, et al. ST2 in patients with severe aortic stenosis and heart failure. Cardiol J 2021; 28: 129-35. 10.5603/CJ.a2019.0052
Kirchhoff C, Habben I, Ivell R, Krull N. A major human epididymis-specific cDNA encodes a protein with sequence homology to extracellular proteinase inhibitors. Biol Reprod 1991; 45: 350-7. 10.1095/biolreprod45.2.350
Hertlein L, Stieber P, Kirschenhofer A, Krocker K, Nagel D, Lenhard M, et al. Human epididymis protein 4 (HE4) in benign and malignant diseases. Clin Chem Lab Med 2012; 50: 2181-8. 10.1515/cclm-2012-0097
Bingle CD, Vyakarnam A. Novel innate immune functions of the whey acidic protein family. Trends Immunol 2008; 29: 444-53. 10.1016/j.it.2008.07.001
de Boer RA, Cao Q, Postmus D, Damman K, Voors AA, Jaarsma T, et al. The WAP four-disulfide core domain protein HE4: a novel biomarker for heart failure. JACC Heart Fail 2013; 1: 164-9. 10.1016/j.jchf.2012.11.005
Piek A, Meijers WC, Schroten NF, Gansevoort RT, de Boer RA, Silljé HH. HE4 serum levels are associated with heart failure severity in patients with chronic heart failure. J Card Fail 2017; 23: 12-9. 10.1016/j.cardfail.2016.05.002
Yamamoto M, Hanatani S, Araki S, Izumiya Y, Yamada T, Nakanishi N, et al. HE4 predicts progressive fibrosis and cardiovascular events in patients with dilated cardiomyopathy. J Am Heart Assoc 2021; 10: e021069. 10.1161/JAHA.120.021069
Hecht S, Giuliani C, Nuche J, Farjat Pasos JI, Bernard J, Tastet L, et al. Multimarker approach to improve risk stratification of patients undergoing transcatheter aortic valve implantation. JACC Adv 2024; 3: 100761. 10.1016/j.jacadv.2023.100761
García R, Villar AV, Cobo M, Llano M, Martín-Durán R, Hurlé MA, et al. Circulating levels of miR-133a predict the regression potential of left ventricular hypertrophy after valve replacement surgery in patients with aortic stenosis. J Am Heart Assoc 2013; 2: e000211. 10.1161/JAHA.113.000211
Dörr O, Walther C, Liebetrau C, Keller T, Sommer T, Boeder N, et al. Galectin-3 and ST2 as predictors of therapeutic success in high-risk patients undergoing percutaneous mitral valve repair (MitraClip). Clin Cardiol 2018; 41: 1164-9. 10.1002/clc.22996
Galeone A, Lessana A, Mascolo E, Di Serio F, Marraudino N, Laborde F, et al. Interleukin-1 receptor-related protein ST2 and mitral valve repair outcome in patients with chronic degenerative mitral regurgitation. Thorac Cardiovasc Surg 2014; 62: 47-51. 10.1055/s-0033-1356751
Clerico A, Carlo Zucchelli G, Pilo A, Passino C, Emdin M. Clinical relevance of biological variation: the lesson of brain natriuretic peptide (BNP) and NT-proBNP assay. Clin Chem Lab Med 2006; 44: 366-78. 10.1515/CCLM.2006.063
Gilard M, Eltchaninoff H, Iung B, Donzeau-Gouge P, Chevreul K, Fajadet J, et al. Registry of transcatheter aortic-valve implantation in high-risk patients. N Engl J Med 2012; 366: 1705-15. 10.1056/NEJMoa1114705
Abdul-Jawad Altisent O, Puri R, Regueiro A, Chamandi C, Rodriguez-Gabella T, Del Trigo M, et al. Predictors and association with clinical outcomes of the changes in exercise capacity after transcatheter aortic valve replacement. Circulation 2017; 136: 632-43. 10.1161/CIRCULATIONAHA.116.026349
Frank D, Stark S, Lutz M, Weissbrodt A, Freitag-Wolf S, Petzina R, et al. Preprocedural high-sensitive troponin predicts survival after transcatheter aortic valve implantation (TAVI). Int J Cardiol 2013; 169: e38-9. 10.1016/j.ijcard.2013.08.108
Chorianopoulos E, Krumsdorf U, Geis N, Pleger ST, Giannitsis E, Katus HA, et al. Preserved prognostic value of preinterventional troponin T levels despite successful TAVI in patients with severe aortic stenosis. Clin Res Cardiol 2014; 103: 65-72. 10.1007/s00392-013-0624-8
Köhler WM, Freitag-Wolf S, Lambers M, Lutz M, Niemann PM, Petzina R, et al. Preprocedural but not periprocedural high-sensitive troponin T levels predict outcome in patients undergoing transcatheter aortic valve implantation. Cardiovasc Ther 2016; 34: 385-96. 10.1111/1755-5922.12208
Vidula MK, Orlenko A, Zhao L, Salvador L, Small AM, Horton E, et al. Plasma biomarkers associated with adverse outcomes in patients with calcific aortic stenosis. Eur J Heart Fail 2021; 23: 2021-32. 10.1002/ejhf.2361
Stundl A, Lünstedt NS, Courtz F, Freitag-Wolf S, Frey N, Holdenrieder S, et al. Soluble ST2 for risk stratification and the prediction of mortality in patients undergoing transcatheter aortic valve implantation. Am J Cardiol 2017; 120: 986-93. 10.1016/j.amjcard.2017.06.033
Wernly B, Lichtenauer M, Jirak P, Eder S, Reiter C, Kammler J, et al. Soluble ST2 predicts 1-year outcome in patients undergoing transcatheter aortic valve implantation. Eur J Clin Invest 2017; 47: 149-57. 10.1111/eci.12719
O'Leary JM, Clavel MA, Chen S, Goel K, O'Neill B, Elmariah S, et al. Association of natriuretic peptide levels after transcatheter aortic valve replacement with subsequent clinical outcomes. JAMA Cardiol 2020; 5: 1113-23. 10.1001/jamacardio.2020.2614
Husser O, Núñez J, Núñez E, Holzamer A, Camboni D, Luchner A, et al. Tumor marker carbohydrate antigen 125 predicts adverse outcome after transcatheter aortic valve implantation. JACC Cardiovasc Interv 2013; 6: 487-96. 10.1016/j.jcin.2013.02.006
Schafer MJ, Atkinson EJ, Vanderboom PM, Kotajarvi B, White TA, Moore MM, et al. Quantification of GDF11 and myostatin in human aging and cardiovascular disease. Cell Metab 2016; 23: 1207-15. 10.1016/j.cmet.2016.05.023
Sinning JM, Wollert KC, Sedaghat A, Widera C, Radermacher MC, Descoups C, et al. Risk scores and biomarkers for the prediction of 1-year outcome after transcatheter aortic valve replacement. Am Heart J 2015; 170: 821-9. 10.1016/j.ahj.2015.07.003
Yamamoto M, Shimura T, Kano S, Kagase A, Kodama A, Sago M, et al. Prognostic value of hypoalbuminemia after transcatheter aortic valve implantation (from the Japanese Multicenter OCEAN-TAVI Registry). Am J Cardiol 2017; 119: 770-7. 10.1016/j.amjcard.2016.11.019
Spangenberg T, Budde U, Schewel D, Frerker C, Thielsen T, Kuck K-H, et al. Treatment of acquired von Willebrand syndrome in aortic stenosis with transcatheter aortic valve replacement. JACC Cardiovasc Interv 2015; 8: 692-700. 10.1016/j.jcin.2015.02.008
Natorska J, Bykowska K, Hlawaty M, Marek G, Sadowski J, Undas A. Increased thrombin generation and platelet activation are associated with deficiency in high molecular weight multimers of von Willebrand factor in patients with moderate-to-severe aortic stenosis. Heart 2011; 97: 2023-8. 10.1136/hrt.2010.217273
Aung N, Dworakowski R, Byrne J, Alcock E, Deshpande R, Rajagopal K, et al. Progressive rise in red cell distribution width is associated with poor outcome after transcatheter aortic valve implantation. Heart 2013; 99: 1261-6. 10.1136/heartjnl-2013-303910
Santos-Faria J, Gavina C, Rodrigues P, Coelho J, da Costa Martins P, Leite-Moreira A, et al. MicroRNAs and ventricular remodeling in aortic stenosis. Rev Port Cardiol 2020; 39: 377-87. 10.1016/j.repc.2019.09.014
Kofler M, Reinstadler SJ, Stastny L, Dumfarth J, Reindl M, Wachter K, et al. Prognostic implications of pre-procedural high-sensitivity cardiac troponin T in patients undergoing transcatheter aortic valve replacement. JACC Cardiovasc Interv 2017; 10: 2345-6. 10.1016/j.jcin.2017.09.020
Fabiani I, Santoni T, Angelillis M, Petricciuolo S, Colli A, Pellegrini G, et al. Growth differentiation factor 15 in severe aortic valve stenosis: relationship with left ventricular remodeling and frailty. J Clin Med 2020; 9: 2998. 10.3390/jcm9092998
Ternacle J, Hecht S, Eltchaninoff H, Salaun E, Clavel M-A, Côté N, et al. Durability of transcatheter aortic valve implantation. EuroIntervention 2024; 20: e845-64. 10.4244/EIJ-D-23-01050
Rodriguez-Gabella T, Voisine P, Dagenais F, Mohammadi S, Perron J, Dumont E, et al. Long-term outcomes following surgical aortic bioprosthesis implantation. J Am Coll Cardiol 2018; 71: 1401-12. 10.1016/j.jacc.2018.01.059
Nollert G, Miksch J, Kreuzer E, Reichart B. Risk factors for atherosclerosis and the degeneration of pericardial valves after aortic valve replacement. J Thorac Cardiovasc Surg 2003; 126: 965-8. 10.1016/S0022-5223(02)73619-2
Ternacle J, Côté N, Krapf L, Nguyen A, Clavel M-A, Pibarot P. Chronic kidney disease and the pathophysiology of valvular heart disease. Can J Cardiol 2019; 35: 1195-207. 10.1016/j.cjca.2019.05.028
Tastet L, Pibarot P, Shen M, Clisson M, Côté N, Salaun E, et al. Oral anticoagulation therapy and progression of calcific aortic valve stenosis. J Am Coll Cardiol 2019; 73: 1869-71. 10.1016/j.jacc.2019.01.043
Salaun E, Mahjoub H, Girerd N, Dagenais F, Voisine P, Mohammadi S, et al. Rate, timing, correlates, and outcomes of hemodynamic valve deterioration after bioprosthetic surgical aortic valve replacement. Circulation 2018; 138: 971-85. 10.1161/CIRCULATIONAHA.118.035150
Lorusso R, Gelsomino S, Lucà F, De Cicco G, Billè G, Carella R, et al. Type 2 diabetes mellitus is associated with faster degeneration of bioprosthetic valve: results from a propensity score-matched Italian multicenter study. Circulation 2012; 125: 604-14. 10.1161/CIRCULATIONAHA.111.025064
Salaun E, Mahjoub H, Dahou A, Mathieu P, Larose É, Després J-P, et al. Hemodynamic deterioration of surgically implanted bioprosthetic aortic valves. J Am Coll Cardiol 2018; 72: 241-51. 10.1016/j.jacc.2018.04.064
Nsaibia MJ, Mahmut A, Mahjoub H, Dahou A, Bouchareb R, Boulanger M-C, et al. Association between plasma lipoprotein levels and bioprosthetic valve structural degeneration. Heart 2016; 102: 1915-21. 10.1136/heartjnl-2016-309541
Mahmut A, Mahjoub H, Boulanger M-C, Fournier D, Després J-P, Pibarot P, et al. Lp-PLA2 is associated with structural valve degeneration of bioprostheses. Eur J Clin Invest 2014; 44: 136-45. 10.1111/eci.12199
Lee S, Levy RJ, Christian AJ, Hazen SL, Frick NE, Lai EK, et al. Calcification and oxidative modifications are associated with progressive bioprosthetic heart valve dysfunction. J Am Heart Assoc 2017; 6: e005648. 10.1161/JAHA.117.005648
Nsaibia MJ, Boulanger MC, Bouchareb R, Mkannez G, Dahou A, Salaun E, et al. Soluble CD14 is associated with the structural failure of bioprostheses. Clin Chim Acta 2018; 485: 173-7. 10.1016/j.cca.2018.06.045
Mahjoub H, Mathieu P, Larose E, Dahou A, Sénéchal M, Dumesnil J-G, et al. Determinants of aortic bioprosthetic valve calcification assessed by multidetector CT. Heart 2015; 101: 472-7. 10.1136/heartjnl-2014-306445
Aykan AÇ, Gökdeniz T, Kalçlk M, Astarcloǧlu MA, Gündüz S, Karakoyun S, et al. Role of anticardiolipin antibodies in the pathogenesis of prosthetic valve thrombosis: an observational study. Herz 2015; 40: 528-33. 10.1007/s00059-013-4038-1
Gürsoy OM, Karakoyun S, Kalçik M, Gökdeniz T, Yesin M, Gündüz S, et al. Usefulness of novel hematologic inflammatory parameters to predict prosthetic mitral valve thrombosis. Am J Cardiol 2014; 113: 860-4. 10.1016/j.amjcard.2013.11.029
Kibler M, Marchandot B, Messas N, Caspar T, Vincent F, Von Hunolstein JJ, et al. CT-ADP point-of-care assay predicts 30-day paravalvular aortic regurgitation and bleeding events following transcatheter aortic valve replacement. Thromb Haemost 2018; 118: 893-905. 10.1055/s-0038-1639352
Schewel D, Frerker C, Schewel J, Wohlmuth P, Meincke F, Thielsen T, et al. Clinical impact of paravalvular leaks on biomarkers and survival after transcatheter aortic valve implantation. Catheter Cardiovasc Interv 2015; 85: 502-14. 10.1002/ccd.25295
Ruiz CE, Hahn RT, Berrebi A, Borer JS, Cutlip DE, Fontana G, et al. Clinical trial principles and endpoint definitions for paravalvular leaks in surgical prosthesis. Eur Heart J 2018; 39: 1224-45. 10.1093/eurheartj/ehx211
Dahou A, Clavel MA, Capoulade R, O'Connor K, Ribeiro HB, Côté N, et al. B-type natriuretic peptide and high-sensitivity cardiac troponin for risk stratification in low-flow, low-gradient aortic stenosis: a substudy of the TOPAS study. JACC Cardiovasc Imaging 2018; 11: 939-47. 10.1016/j.jcmg.2017.06.018
Lindman BR, Clavel MA, Abu-Alhayja'a R, Côté N, Dagenais F, Novak E, et al. Multimarker approach to identify patients with higher mortality and rehospitalization rate after surgical aortic valve replacement for aortic stenosis. JACC Cardiovasc Interv 2018; 11: 2172-81. 10.1016/j.jcin.2018.07.039
