Skip to main content

Advertisement

SpringerLink
Log in

Left ventricular fibrosis and CMR tissue characterization of papillary muscles in mitral valve prolapse patients

  • Original Paper
  • Published:
The International Journal of Cardiovascular Imaging Aims and scope Submit manuscript

Abstract

Purpose

Mitral valve prolapse (MVP) is associated with left ventricle (LV) fibrosis, including the papillary muscles (PM), which is in turn linked to malignant arrhythmias. This study aims to evaluate comprehensive tissue characterization of the PM by cardiovascular magnetic resonance (CMR) imaging and its association with LV fibrosis observed by intraoperative biopsies.

Methods

MVP patients with indication for surgery due to severe mitral regurgitation (n = 19) underwent a preoperative CMR with characterization of the PM: dark-appearance on cine, T1 mapping, conventional bright blood (BB) and dark blood (DB) late gadolinium enhancement (LGE). CMR T1 mapping was performed on 21 healthy volunteers as controls. LV inferobasal myocardial biopsies were obtained in MVP patients and compared to CMR findings.

Results

MVP patients (54 ± 10 years old, 14 male) had a dark-appearance of the PM with higher native T1 and extracellular volume (ECV) values compared with healthy volunteers (1096 ± 78ms vs. 994 ± 54ms and 33.9 ± 5.6% vs. 25.9 ± 3.1%, respectively, p < 0.001). Seventeen MVP patients (89.5%) had fibrosis by biopsy. BB-LGE + in LV and PM was identified in 5 (26.3%) patients, while DB-LGE + was observed in LV in 9 (47.4%) and in PM in 15 (78.9%) patients. DB-LGE + in PM was the only technique that showed no difference with detection of LV fibrosis by biopsy. Posteromedial PM was more frequently affected than the anterolateral (73.7% vs. 36.8%, p = 0.039) and correlated with biopsy-proven LV fibrosis (Rho 0.529, p = 0.029).

Conclusions

CMR imaging in MVP patients referred for surgery shows a dark-appearance of the PM with higher T1 and ECV values compared with healthy volunteers. The presence of a positive DB-LGE at the posteromedial PM by CMR may serve as a better predictor of biopsy-proven LV inferobasal fibrosis than conventional CMR techniques.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Abbreviations

BB:

Bright blood (conventional)

CMR:

Cardiovascular magnetic resonance

CVF:

Connective tissue volume fraction

DB:

Dark blood

ECV:

Extracellular volume

LGE:

Late gadolinium enhancement

LV:

Left ventricle

MVP:

Mitral valve prolapse

PM:

Papillary muscle

PMal:

Anterolateral papillary muscle

PMpm:

Posteromedial papillary muscle

References

  1. Levine RA, Hagege AA, Judge DP, Padala M, Dal-Bianco JP, Aikawa E et al (2015) Mitral valve Disease–morphology and mechanisms. Nat Rev Cardiol 12(12):689–710

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Basso C, Perazzolo Marra M, Rizzo S, De Lazzari M, Giorgi B, Cipriani A et al (2015) Arrhythmic mitral valve prolapse and Sudden Cardiac Death. Circulation 132(7):556–566

    Article  PubMed  Google Scholar 

  3. Han HC, Parsons SA, Curl CL, Teh AW, Raaijmakers AJA, Koshy AN et al (2021) Systematic quantification of histologic ventricular fibrosis in isolated mitral valve prolapse and Sudden Cardiac Death. Heart Rhythm 18(4):570–576

    Article  PubMed  Google Scholar 

  4. Morningstar JE, Gensemer C, Moore R, Fulmer D, Beck TC, Wang C et al (2021) Mitral valve prolapse induces regionalized myocardial fibrosis. J Am Heart Assoc 10(24):e022332

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Constant Dit Beaufils AL, Huttin O, Jobbe-Duval A, Senage T, Filippetti L, Piriou N et al (2021) Replacement myocardial fibrosis in patients with mitral valve prolapse: relation to mitral regurgitation, ventricular remodeling, and Arrhythmia. Circulation 143(18):1763–1774

    Article  PubMed  Google Scholar 

  6. Kitkungvan D, Nabi F, Kim RJ, Bonow RO, Khan MA, Xu J et al (2018) Myocardial fibrosis in patients with primary mitral regurgitation with and without Prolapse. J Am Coll Cardiol 72(8):823–834

    Article  PubMed  Google Scholar 

  7. Muthukumar L, Rahman F, Jan MF, Shaikh A, Kalvin L, Dhala A et al (2017) The Pickelhaube sign: novel echocardiographic risk marker for malignant mitral valve prolapse syndrome. JACC Cardiovasc Imaging 10(9):1078–1080

    Article  PubMed  Google Scholar 

  8. Sanfilippo AJ, Harrigan P, Popovic AD, Weyman AE, Levine RA (1992) Papillary muscle traction in mitral valve prolapse: quantitation by two-dimensional echocardiography. J Am Coll Cardiol 19(3):564–571

    Article  CAS  PubMed  Google Scholar 

  9. Park MH, van Kampen A, Melnitchouk S, Wilkerson RJ, Nagata Y, Zhu Y et al (2022) Native and post-repair residual mitral valve prolapse increases forces exerted on the papillary muscles: a possible mechanism for localized fibrosis? Circ Cardiovasc Interv 15(12):e011928

    Article  PubMed  PubMed Central  Google Scholar 

  10. Enriquez A, Shirai Y, Huang J, Liang J, Briceno D, Hayashi T et al (2019) Papillary muscle ventricular arrhythmias in patients with arrhythmic mitral valve prolapse: electrophysiologic substrate and catheter ablation outcomes. J Cardiovasc Electrophysiol 30(6):827–835

    Article  PubMed  Google Scholar 

  11. Nagata Y, Bertrand PB, Levine RA (2022) Malignant mitral valve prolapse: risk and Prevention of Sudden Cardiac Death. Curr Treat Options Cardiovasc Med 24(5):61–86

    Article  PubMed  PubMed Central  Google Scholar 

  12. Bui AH, Roujol S, Foppa M, Kissinger KV, Goddu B, Hauser TH et al (2017) Diffuse myocardial fibrosis in patients with mitral valve prolapse and ventricular arrhythmia. Heart 103(3):204–209

    Article  PubMed  Google Scholar 

  13. Lim SJ, Koo HJ, Cho MS, Nam GB, Kang JW, Yang DH (2021) Late Gadolinium Enhancement of Left ventricular papillary muscles in patients with mitral regurgitation. Korean J Radiol 22(10):1609–1618

    Article  PubMed  PubMed Central  Google Scholar 

  14. Han Y, Peters DC, Salton CJ, Bzymek D, Nezafat R, Goddu B et al (2008) Cardiovascular magnetic resonance characterization of mitral valve prolapse. JACC Cardiovasc Imaging 1(3):294–303

    Article  PubMed  Google Scholar 

  15. Van De Heyning CM, Holtackers RJ, Nazir MS, Grapsa J, Demetrescu C, Pype L et al (2022) Dark-blood late gadolinium enhancement CMR improves detection of papillary muscle fibrosis in patients with mitral valve prolapse. Eur J Radiol 147:110118

    Article  PubMed  Google Scholar 

  16. Scatteia A, Pascale CE, Gallo P, Pezzullo S, America R, Cappelletti AM et al (2020) Abnormal papillary Muscle Signal on Cine MRI as a typical feature of mitral valve prolapse. Sci Rep 10(1):9166

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  17. Karamitsos TD, Arvanitaki A, Karvounis H, Neubauer S, Ferreira VM (2020) Myocardial tissue characterization and fibrosis by imaging. JACC Cardiovasc Imaging 13(5):1221–1234

    Article  PubMed  Google Scholar 

  18. Gupta S, Ge Y, Singh A, Grani C, Kwong RY (2021) Multimodality Imaging Assessment of Myocardial Fibrosis. JACC Cardiovasc Imaging 14(12):2457–2469

    Article  PubMed  Google Scholar 

  19. Kitkungvan D, Yang EY, El Tallawi KC, Nagueh SF, Nabi F, Khan MA et al (2021) Extracellular volume in primary mitral regurgitation. JACC Cardiovasc Imaging 14(6):1146–1160

    Article  PubMed  Google Scholar 

  20. Zoghbi WA, Adams D, Bonow RO, Enriquez-Sarano M, Foster E, Grayburn PA et al (2017) Recommendations for noninvasive evaluation of native valvular regurgitation: a report from the American Society of Echocardiography Developed in Collaboration with the Society for Cardiovascular Magnetic Resonance. J Am Soc Echocardiogr 30(4):303–371

    Article  PubMed  Google Scholar 

  21. Lancellotti P, Pibarot P, Chambers J, La Canna G, Pepi M, Dulgheru R et al (2022) Multi-modality imaging assessment of native valvular regurgitation: an EACVI and ESC council of valvular Heart Disease position paper. Eur Heart J Cardiovasc Imaging 23(5):e171–e232

    Article  PubMed  Google Scholar 

  22. Kramer CM, Barkhausen J, Flamm SD, Kim RJ, Nagel E (2013) Society for Cardiovascular Magnetic Resonance Board of Trustees Task Force on standardized P. standardized cardiovascular magnetic resonance (CMR) protocols 2013 update. J Cardiovasc Magn Reson 15:91

    Article  PubMed  PubMed Central  Google Scholar 

  23. Spampinato RA, Jahnke C, Crelier G, Lindemann F, Fahr F, Czaja-Ziolkowska M et al (2021) Quantification of regurgitation in mitral valve prolapse with four-dimensional flow cardiovascular magnetic resonance. J Cardiovasc Magn Reson 23(1):87

    Article  PubMed  PubMed Central  Google Scholar 

  24. Miles C, Westaby J, Ster IC, Asimaki A, Boardman P, Joshi A et al (2020) Morphometric characterization of collagen and fat in normal ventricular myocardium. Cardiovasc Pathol 48:107224

    Article  PubMed  PubMed Central  Google Scholar 

  25. Liu B, Neil DAH, Bhabra M, Patel R, Barker TA, Nikolaidis N et al (2022) Reverse myocardial remodeling following valve repair in patients with chronic severe primary degenerative mitral regurgitation. JACC Cardiovasc Imaging 15(2):224–236

    Article  PubMed  Google Scholar 

  26. Liu B, Neil DAH, Premchand M, Bhabra M, Patel R, Barker T et al (2020) Myocardial fibrosis in asymptomatic and symptomatic chronic severe primary mitral regurgitation and relationship to tissue characterisation and left ventricular function on cardiovascular magnetic resonance. J Cardiovasc Magn Resonance: Official J Soc Cardiovasc Magn Reson 22(1):86

    Article  Google Scholar 

  27. Van De Heyning CM, Magne J, Pierard LA, Bruyere PJ, Davin L, De Maeyer C et al (2014) Late gadolinium enhancement CMR in primary mitral regurgitation. Eur J Clin Invest 44(9):840–847

    Article  PubMed  Google Scholar 

  28. Bumgarner JM, Patel D, Kumar A, Clevenger JR, Trulock KM, Popovic Z et al (2019) Management and outcomes in mitral valve prolapse with ventricular arrhythmias undergoing ablation and/or implantation of ICDs. Pacing Clin Electrophysiol 42(4):447–452

    Article  PubMed  Google Scholar 

  29. Han Y, Peters DC, Kissinger KV, Goddu B, Yeon SB, Manning WJ et al (2010) Evaluation of papillary muscle function using cardiovascular magnetic resonance imaging in mitral valve prolapse. Am J Cardiol 106(2):243–248

    Article  PubMed  PubMed Central  Google Scholar 

  30. Kilicgedik A, Kahveci G, Gurbuz AS, Karabay CY, Guler A, Efe SC et al (2017) Papillary muscle free strain in patients with severe degenerative and functional mitral regurgitation. Arq Bras Cardiol 108(4):339–346

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Perazzolo Marra M, Basso C, De Lazzari M, Rizzo S, Cipriani A, Giorgi B et al (2016) Morphofunctional Abnormalities of Mitral Annulus and arrhythmic mitral valve prolapse. Circ Cardiovasc Imaging 9(8):e005030

    Article  PubMed  PubMed Central  Google Scholar 

  32. Stephens SE, Kammien AJ, Paris JC, Applequist AP, Ingels NB, Jensen HK et al (2022) In Vitro Mitral Valve Model with Unrestricted Ventricular Access: using Vacuum to close the Valve and Enable Static Trans-Mitral pressure. J Cardiovasc Transl Res 15(4):845–854

    Article  PubMed  PubMed Central  Google Scholar 

  33. Ahmed MI, Andrikopoulou E, Zheng J, Ulasova E, Pat B, Kelley EE et al (2022) Interstitial Collagen Loss, myocardial remodeling, and function in primary mitral regurgitation. JACC Basic Transl Sci 7(10):973–981

    Article  PubMed  PubMed Central  Google Scholar 

  34. Dejgaard LA, Skjolsvik ET, Lie OH, Ribe M, Stokke MK, Hegbom F et al (2018) The mitral Annulus Disjunction Arrhythmic Syndrome. J Am Coll Cardiol 72(14):1600–1609

    Article  PubMed  Google Scholar 

  35. Basso C, Iliceto S, Thiene G, Perazzolo Marra M (2019) Mitral valve prolapse, ventricular arrhythmias, and Sudden Death. Circulation 140(11):952–964

    Article  PubMed  Google Scholar 

  36. Vahanian A, Beyersdorf F, Praz F, Milojevic M, Baldus S, Bauersachs J et al (2021) 2021 ESC/EACTS guidelines for the management of valvular Heart Disease. Eur J cardio-thoracic Surgery: Official J Eur Association Cardio-thoracic Surg 60(4):727–800

    Article  Google Scholar 

  37. Otto CM, Nishimura RA, Bonow RO, Carabello BA, Erwin JP 3rd, Gentile F et al (2021) 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. Circulation 143(5):e72–e227

    PubMed  Google Scholar 

Download references

Acknowledgements

Not applicable.

Author information

Author notes

  1. Ricardo A. Spampinato and Mateo Marin-Cuartas contributed equally.

  2. Ingo Paetsch and Michael A. Borger are co-senior responsible authors.

Authors and Affiliations

  1. Department of Cardiac Surgery, University, Leipzig Heart Center, Struempellstrasse 39, 04289, Leipzig, Germany

    Ricardo A. Spampinato, Mateo Marin-Cuartas, Antonia van Kampen, Florian Fahr, Franz Sieg, Elfriede Strotdrees, Kristin Klaeske, Karoline Wiesner, Maja-Theresa Dieterlen & Michael A. Borger

  2. Department of Cardiology and Electrophysiology, Leipzig Heart Center, Leipzig, Germany

    Cosima Jahnke & Ingo Paetsch

  3. Division of Cardiac Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    Antonia van Kampen

  4. Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC, USA

    Jordan E. Morningstar & Russell A. Norris

  5. Cardiac Ultrasound Laboratory, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    Yasufumi Nagata & Robert A. Levine

  6. The Institute for Innovation in Imaging, Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    David Izquierdo-Garcia

Authors
  1. Ricardo A. Spampinato
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mateo Marin-Cuartas
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Antonia van Kampen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Florian Fahr
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Franz Sieg
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Elfriede Strotdrees
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Cosima Jahnke
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Kristin Klaeske
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Karoline Wiesner
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Jordan E. Morningstar
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Yasufumi Nagata
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. David Izquierdo-Garcia
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Maja-Theresa Dieterlen
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Russell A. Norris
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Robert A. Levine
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Ingo Paetsch
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Michael A. Borger
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

MAB, RAS, MM-C, MT-D, RAN, CJ, IP, and RAL were involved in the conception and design of the study. RAS, MM-C, FF, FS, MT-D, KK, KW, AVK, ES, CJ, and IP were involved in data collection. RAS, MM-C, MT-D, and MAB were involved in data analyses. RAS, MM-C, MAB and MT-D were responsible for statistical analyses. RAS and MM-C were responsible for drafting of manuscript. RAS, MM-C, MT-D, JEM, YN, DI-G, RAN, RAL and MAB were responsible for critically revising the manuscript for important intellectual content. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Ricardo A. Spampinato.

Ethics declarations

Competing interests

The authors declare no competing interests.

Ethics approval and consent to participate

The study was conducted in accordance with the Declaration of Helsinki, and was approved by the local research ethics committee (450-18-ek). All subjects gave written informed consent prior to study initiation.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Additional file 1: Appendix. Histology and CMR Acquisition details

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Spampinato, R.A., Marin-Cuartas, M., van Kampen, A. et al. Left ventricular fibrosis and CMR tissue characterization of papillary muscles in mitral valve prolapse patients. Int J Cardiovasc Imaging 40, 213–224 (2024). https://doi.org/10.1007/s10554-023-02985-w

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10554-023-02985-w

Keywords

Search

Navigation