Observational Study

Myocardial fibrosis in aortic stenosis: comparison between clinical data, laboratory, echocardiography, and cardiac magnetic resonance

Giuseppe Tosto, Giulia Passaniti, Fortunata Alessandra Gibiino, Wanda Deste*, Antonino Indelicato, Tito Torrisi, Giuseppe Bottaro, Maria Teresa Cannizzaro and Corrado Tamburino

Published: 16 May, 2023 | Volume 8 - Issue 2 | Pages: 051-058

Introduction: Patients with aortic stenosis often develop hypertrophy and fibrosis, regardless of symptoms. Cardiac Magnetic Resonance (CMR) represents the gold standard for the evaluation of fibrosis despite numerous limitations: cost, availability, atrial fibrillation, claustrophobia, kidney failure or inability to apnea.
Purpose: The aim is to validate the role of echocardiographic parameters, such as Global Longitudinal Strain (GLS), as early markers of fibrosis. Clinical and laboratory data, particularly B-type Natriuretic Peptide (BNP), were also analyzed.
Material and methods: In our study we recruited 33 patients with severe aortic stenosis, correlating echocardiographic values of GLS with the qualitative analysis of Late Gadolinium Enhancement (LGE) and the quantitative analysis of T1 mapping of CMR.
Results: 70% of patients with an alteration of GLS had LGE+. Univariate logistic regression shows that the factors associated with the presence of LGE on CMR are hypertension (p = 0.043), GLS (p = 0.032), and elevated BNP values (p = 0.021); for GLS, Odds Ratio (OR) is 5 so the chance of finding fibrosis on CMR increases 5 times in presence of an altered GLS. The multivariate analysis confirms the association with impaired GLS values (p = 0.033) and hypertension (p = 0.025), but not with elevated Pro-BNP values.
Conclusion: In patients with severe aortic stenosis, the association between GLS, LGE, and T1 mapping can help identify earlier those patients with structural changes caused by the disease, who could benefit from early intervention. It remains to be established how the presence of these alterations has a role in determining the intervention time and the outcome of these patients.

Read Full Article HTML DOI: 10.29328/journal.jccm.1001153 Cite this Article Read Full Article PDF


Aortic stenosis; Global longitudinal strain; Cardiac magnetic resonance; Fibrosis; Late gadolinium enhancement


  1. Otto CM, Prendergast B. Aortic-valve stenosis--from patients at risk to severe valve obstruction. N Engl J Med. 2014 Aug 21;371(8):744-56. doi: 10.1056/NEJMra1313875. PMID: 25140960.
  2. Delgado V, Bax JJ. Will Cardiac Magnetic Resonance Change the Management of Severe Aortic Stenosis Patients? JACC Cardiovasc Imaging. 2018 Jul;11(7):984-986. doi: 10.1016/j.jcmg.2017.11.039. PMID: 29976304.
  3. Unverferth DV, Baker PB, Swift SE, Chaffee R, Fetters JK, Uretsky BF, Thompson ME, Leier CV. Extent of myocardial fibrosis and cellular hypertrophy in dilated cardiomyopathy. Am J Cardiol. 1986 Apr 1;57(10):816-20. doi: 10.1016/0002-9149(86)90620-x. PMID: 2938462.
  4. Chin CWL, Everett RJ, Kwiecinski J, Vesey AT, Yeung E, Esson G, Jenkins W, Koo M, Mirsadraee S, White AC, Japp AG, Prasad SK, Semple S, Newby DE, Dweck MR. Myocardial Fibrosis and Cardiac Decompensation in Aortic Stenosis. JACC Cardiovasc Imaging. 2017 Nov;10(11):1320-1333. doi: 10.1016/j.jcmg.2016.10.007. Epub 2016 Dec 21. PMID: 28017384; PMCID: PMC5683736.
  5. Anderson KR, Sutton MG, Lie JT. Histopathological types of cardiac fibrosis in myocardial disease. J Pathol. 1979 Jun;128(2):79-85. doi: 10.1002/path.1711280205. PMID: 572867.
  6. Hein S, Arnon E, Kostin S, Schönburg M, Elsässer A, Polyakova V, Bauer EP, Klövekorn WP, Schaper J. Progression from compensated hypertrophy to failure in the pressure-overloaded human heart: structural deterioration and compensatory mechanisms. Circulation. 2003 Feb 25;107(7):984-91. doi: 10.1161/01.cir.0000051865.66123.b7. PMID: 12600911.
  7. Chin CWL, Everett RJ, Kwiecinski J, Vesey AT, Yeung E, Esson G, Jenkins W, Koo M, Mirsadraee S, White AC, Japp AG, Prasad SK, Semple S, Newby DE, Dweck MR. Myocardial Fibrosis and Cardiac Decompensation in Aortic Stenosis. JACC Cardiovasc Imaging. 2017 Nov;10(11):1320-1333. doi: 10.1016/j.jcmg.2016.10.007. Epub 2016 Dec 21. PMID: 28017384; PMCID: PMC5683736.
  8. Dweck MR, Joshi S, Murigu T, Alpendurada F, Jabbour A, Melina G, Banya W, Gulati A, Roussin I, Raza S, Prasad NA, Wage R, Quarto C, Angeloni E, Refice S, Sheppard M, Cook SA, Kilner PJ, Pennell DJ, Newby DE, Mohiaddin RH, Pepper J, Prasad SK. Midwall fibrosis is an independent predictor of mortality in patients with aortic stenosis. J Am Coll Cardiol. 2011 Sep 13;58(12):1271-9. doi: 10.1016/j.jacc.2011.03.064. PMID: 21903062.
  9. Baumgartner H Chair, Hung J Co-Chair, Bermejo J, Chambers JB, Edvardsen T, Goldstein S, Lancellotti P, LeFevre M, Miller F Jr, Otto CM. Recommendations on the echocardiographic assessment of aortic valve stenosis: a focused update from the European Association of Cardiovascular Imaging and the American Society of Echocardiography. Eur Heart J Cardiovasc Imaging. 2017 Mar 1;18(3):254-275. doi: 10.1093/ehjci/jew335. PMID: 28363204.
  10. Barone-Rochette G, Piérard S, De Meester de Ravenstein C, Seldrum S, Melchior J, Maes F, Pouleur AC, Vancraeynest D, Pasquet A, Vanoverschelde JL, Gerber BL. Prognostic significance of LGE by CMR in aortic stenosis patients undergoing valve replacement. J Am Coll Cardiol. 2014 Jul 15;64(2):144-54. doi: 10.1016/j.jacc.2014.02.612. PMID: 25011718.
  11. Bottaro G, Zappulla P, Deste W, Famà F, Agnello F, Trovato D, Indelicato A, Barbanti M, Sgroi C, Monte IP, Tamburino C. Severe Aortic Valve Stenosis: Symptoms, Biochemical Markers, and Global Longitudinal Strain. J Cardiovasc Echogr. 2020 Jul-Sep;30(3):154-161. doi: 10.4103/jcecho.jcecho_13_20. Epub 2020 Nov 9. PMID: 33447506; PMCID: PMC7799072.
  12. Park SJ, Cho SW, Kim SM, Ahn J, Carriere K, Jeong DS, Lee SC, Park SW, Choe YH, Park PW, Oh JK. Assessment of Myocardial Fibrosis Using Multimodality Imaging in Severe Aortic Stenosis: Comparison With Histologic Fibrosis. JACC Cardiovasc Imaging. 2019 Jan;12(1):109-119. doi: 10.1016/j.jcmg.2018.05.028. Epub 2018 Nov 15. PMID: 30448148.
  13. Le TT, Huang W, Singh GK, Toh DF, Ewe SH, Tang HC, Loo G, Bryant JA, Ang B, Tay EL, Soo WM, Yip JW, Oon YY, Gong L, Lunaria JB, Yong QW, Lee EM, Yeo PSD, Chai SC, Goh PP, Ling LF, Ong HY, Richards AM, Delgado V, Bax JJ, Ding ZP, Ling LH, Chin CWL. Echocardiographic Global Longitudinal Strain Is Associated With Myocardial Fibrosis and Predicts Outcomes in Aortic Stenosis. Front Cardiovasc Med. 2021 Nov 10;8:750016. doi: 10.3389/fcvm.2021.750016. PMID: 34859068; PMCID: PMC8631398.
  14. Klaeboe LG, Haland TF, Leren IS, Ter Bekke RMA, Brekke PH, Røsjø H, Omland T, Gullestad L, Aakhus S, Haugaa KH, Edvardsen T. Prognostic Value of Left Ventricular Deformation Parameters in Patients with Severe Aortic Stenosis: A Pilot Study of the Usefulness of Strain Echocardiography. J Am Soc Echocardiogr. 2017 Aug;30(8):727-735.e1. doi: 10.1016/j.echo.2017.04.009. Epub 2017 Jun 7. PMID: 28599826.
  15. Kearney LG, Lu K, Ord M, Patel SK, Profitis K, Matalanis G, Burrell LM, Srivastava PM. Global longitudinal strain is a strong independent predictor of all-cause mortality in patients with aortic stenosis. Eur Heart J Cardiovasc Imaging. 2012 Oct;13(10):827-33. doi: 10.1093/ehjci/jes115. Epub 2012 Jun 26. PMID: 22736713.
  16. Ng AC, Delgado V, Bertini M, Antoni ML, van Bommel RJ, van Rijnsoever EP, van der Kley F, Ewe SH, Witkowski T, Auger D, Nucifora G, Schuijf JD, Poldermans D, Leung DY, Schalij MJ, Bax JJ. Alterations in multidirectional myocardial functions in patients with aortic stenosis and preserved ejection fraction: a two-dimensional speckle tracking analysis. Eur Heart J. 2011 Jun;32(12):1542-50. doi: 10.1093/eurheartj/ehr084. Epub 2011 Mar 29. PMID: 21447510.
  17. Kusunose K, Goodman A, Parikh R, Barr T, Agarwal S, Popovic ZB, Grimm RA, Griffin BP, Desai MY. Incremental prognostic value of left ventricular global longitudinal strain in patients with aortic stenosis and preserved ejection fraction. Circ Cardiovasc Imaging. 2014 Nov;7(6):938-45. doi: 10.1161/CIRCIMAGING.114.002041. Epub 2014 Oct 15. PMID: 25320287.
  18. Vassiliou VS, Perperoglou A, Raphael CE, Joshi S, Malley T, Everett R, Halliday B, Pennell DJ, Dweck MR, Prasad SK. Midwall Fibrosis and 5-Year Outcome in Moderate and Severe Aortic Stenosis. J Am Coll Cardiol. 2017 Apr 4;69(13):1755-1756. doi: 10.1016/j.jacc.2017.01.034. PMID: 28359524.
  19. Spath NB, Gomez M, Everett RJ, Semple S, Chin CWL, White AC, Japp AG, Newby DE, Dweck MR. Global Longitudinal Strain Analysis Using Cardiac MRI in Aortic Stenosis: Comparison with Left Ventricular Remodeling, Myocardial Fibrosis, and 2-year Clinical Outcomes. Radiol Cardiothorac Imaging. 2019 Oct 31;1(4):e190027. doi: 10.1148/ryct.2019190027. PMID: 33778518; PMCID: PMC7977929.
  20. Bull S, White SK, Piechnik SK, Flett AS, Ferreira VM, Loudon M, Francis JM, Karamitsos TD, Prendergast BD, Robson MD, Neubauer S, Moon JC, Myerson SG. Human non-contrast T1 values and correlation with histology in diffuse fibrosis. Heart. 2013 Jul;99(13):932-7. doi: 10.1136/heartjnl-2012-303052. Epub 2013 Jan 24. PMID: 23349348; PMCID: PMC3686317.
  21. Kockova R, Kacer P, Pirk J, Maly J, Sukupova L, Sikula V, Kotrc M, Barciakova L, Honsova E, Maly M, Kautzner J, Sedmera D, Penicka M. Native T1 Relaxation Time and Extracellular Volume Fraction as Accurate Markers of Diffuse Myocardial Fibrosis in Heart Valve Disease - Comparison With Targeted Left Ventricular Myocardial Biopsy. Circ J. 2016 Apr 25;80(5):1202-9. doi: 10.1253/circj.CJ-15-1309. Epub 2016 Mar 17. PMID: 26984717.
  22. Chin CWL, Everett RJ, Kwiecinski J, Vesey AT, Yeung E, Esson G, Jenkins W, Koo M, Mirsadraee S, White AC, Japp AG, Prasad SK, Semple S, Newby DE, Dweck MR. Myocardial Fibrosis and Cardiac Decompensation in Aortic Stenosis. JACC Cardiovasc Imaging. 2017 Nov;10(11):1320-1333. doi: 10.1016/j.jcmg.2016.10.007. Epub 2016 Dec 21. PMID: 28017384; PMCID: PMC5683736.
  23. Lee H, Park JB, Yoon YE, Park EA, Kim HK, Lee W, Kim YJ, Cho GY, Sohn DW, Greiser A, Lee SP. Noncontrast Myocardial T1 Mapping by Cardiac Magnetic Resonance Predicts Outcome in Patients With Aortic Stenosis. JACC Cardiovasc Imaging. 2018 Jul;11(7):974-983. doi: 10.1016/j.jcmg.2017.09.005. Epub 2017 Nov 15. PMID: 29153562.
  24. Castrichini M, Vitrella G, De Luca A, Altinier A, Korcova R, Pagura L, Radesich C, Sinagra G. Clinical impact of myocardial fibrosis in severe aortic stenosis. Eur Heart J Suppl. 2021 Oct 8;23(Suppl E):E147-E150. doi: 10.1093/eurheartj/suab120. PMID: 34650375; PMCID: PMC8503407.
  25. Bing R, Cavalcante JL, Everett RJ, Clavel MA, Newby DE, Dweck MR. Imaging and Impact of Myocardial Fibrosis in Aortic Stenosis. JACC Cardiovasc Imaging. 2019 Feb;12(2):283-296. doi: 10.1016/j.jcmg.2018.11.026. PMID: 30732723; PMCID: PMC6361867.


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