Keywords
hyperuricemia
heart valves
extraarticular urate deposits
tophaceus valve
X-Ray computed tomography
Categories
How to Cite
Abstract
While the extraarticular deposition of urate crystals and its general cardiovascular impact are well recognized, the specific association between hyperuricemia and heart valve disease remains under-documented. Currently, only isolated cases of tophaceous valves have been reported, highlighting a significant gap in the literature. This narrative review aims to investigate the available data on monosodium urate (MSU) deposition on heart valves, assessing its prevalence, detection via advanced imaging modalities, and potential contribution to structural valve dysfunction. A literature search was conducted in the PubMed (MEDLINE) database for records published up to April 2026. The search strategy utilized Boolean operators to combine terms for specific heart valves with “gout,” “urate crystals,” “tophi,” and imaging modalities relevant to extraarticular gout. Relevant case reports, imaging studies, and primary references were curated and analyzed. The search identified 10 historical case reports and one systematic review detailing histologically proven tophaceous valves, predominantly affecting the mitral and aortic valves. Historically, valvular tophi were considered exceedingly rare, often manifesting as incidental postmortem or postoperative findings. However, recent data utilizing Dual-Energy Computed Tomography (DECT) contrasts this paradigm. A prominent DECT study revealed cardiovascular MSU deposition in 86.4% of gout patients, with 18.2% specifically exhibiting urate deposits within the heart valves. These imaging findings were histologically validated, demonstrating DECT's accuracy in differentiating MSU from typical degenerative calcinosis, which may macroscopically mask urate deposits during routine histopathological examinations. Although isolated case reports suggest valvular tophi are rare, advanced imaging reveals a significantly higher prevalence of MSU deposits in cardiac valves. This discrepancy highlights the necessity for increased clinical vigilance regarding valvular involvement in hyperuricemic individuals and warrants further investigation into its precise role in structural heart disease.
References
1. Dehlin M, Jacobsson L, Roddy E. Global epidemiology of gout: prevalence, incidence, treatment patterns and risk factors. Nat Rev Rheumatol. 2020 Jul;16(7):380-390. doi: 10.1038/s41584-020-0441-1.
2. Safiri S, Kolahi AA, Cross M, Carson-Chahhoud K, Hoy D, Almasi-Hashiani A, Sepidarkish M, Ashrafi-Asgarabad A, Moradi-Lakeh M, Mansournia MA, Kaufman JS, Collins G, Woolf AD, March L, Smith E. Prevalence, Incidence, and Years Lived With Disability Due to Gout and Its Attributable Risk Factors for 195 Countries and Territories 1990-2017: A Systematic Analysis of the Global Burden of Disease Study 2017. Arthritis Rheumatol. 2020 Nov;72(11):1916-1927. doi: 10.1002/art.41404.
3. GBD 2021 Gout Collaborators. Global, regional, and national burden of gout, 1990-2020, and projections to 2050: a systematic analysis of the Global Burden of Disease Study 2021. Lancet Rheumatol. 2024 Aug;6(8):e507-e517. doi: 10.1016/S2665-9913(24)00117-6. Epub 2024 Jul 9. Erratum in: Lancet Rheumatol. 2024 Nov;6(11):e749. doi: 10.1016/S2665-9913(24)00303-5.
4. Mikuls TR. Gout. N Engl J Med. 2022 Nov 17;387(20):1877-1887. doi: 10.1056/NEJMcp2203385.
5. Johnson R, Gruev I, Yotov Y, Jackuliak P, Borghi C, Domienik-Karłowicz J, Tykarski A, Filipiak KJ, Jaguszewski MJ, Narkiewicz K, Barylski M, Mamcarz A, Wolf J, Jarai Z, Becer D, Vrablik M, Vinereanu D, Wełnicki M, Widecka K, Litwin M. Expert consensus for the diagnosis and treatment of patients with hyperuricemia and high cardiovascular risk: 2025 update. Eur J Intern Med. 2026 Apr;146:106727. doi: 10.1016/j.ejim.2026.106727.
6. Borghi C, Agabiti-Rosei E, Johnson RJ, Kielstein JT, Lurbe E, Mancia G, Redon J, Stack AG, Tsioufis KP. Hyperuricaemia and gout in cardiovascular, metabolic and kidney disease. Eur J Intern Med. 2020 Oct;80:1-11. doi: 10.1016/j.ejim.2020.07.006.
7. FitzGerald JD, Dalbeth N, Mikuls T, Brignardello-Petersen R, Guyatt G, Abeles AM, Gelber AC, Harrold LR, Khanna D, King C, Levy G, Libbey C, Mount D, Pillinger MH, Rosenthal A, Singh JA, Sims JE, Smith BJ, Wenger NS, Bae SS, Danve A, Khanna PP, Kim SC, Lenert A, Poon S, Qasim A, Sehra ST, Sharma TSK, Toprover M, Turgunbaev M, Zeng L, Zhang MA, Turner AS, Neogi T. 2020 American College of Rheumatology Guideline for the Management of Gout. Arthritis Rheumatol. 2020 Jun;72(6):879-895. doi: 10.1002/art.41247. Epub 2020 May 11. Erratum in: Arthritis Rheumatol. 2021 Mar;73(3):413. doi: 10.1002/art.41688.
8. Yip K, Cohen RE, Pillinger MH. Asymptomatic hyperuricemia: is it really asymptomatic? Curr Opin Rheumatol. 2020 Jan;32(1):71-79. doi: 10.1097/BOR.0000000000000679.
9. Towiwat P, Chhana A, Dalbeth N. The anatomical pathology of gout: a systematic literature review. BMC Musculoskelet Disord. 2019 Apr 1;20(1):140. doi: 10.1186/s12891-019-2519-y.
10. Forbess LJ, Fields TR. The broad spectrum of urate crystal deposition: unusual presentations of gouty tophi. Semin Arthritis Rheum. 2012 Oct;42(2):146-54. doi: 10.1016/j.semarthrit.2012.03.007.
11. Koley S, Salodkar A, Choudhary S, Bhake A, Singhania K, Choudhury M. Tophi as first manifestation of gout. Indian J Dermatol Venereol Leprol. 2010;76(4):393-396. doi: 10.4103/0378-6323.66593.
12. Cohen-Rosenblum AR, Somogyi JR, Hynes KK, Guevara ME. Orthopaedic management of gout. J Am Acad Orthop Surg Glob Res Rev. 2022;6(11):e22.00216. doi: 10.5435/JAAOSGlobal-D-22-00216.
13. Luo SF, Chin CY, Ho LJ, Tseng WY, Kuo CF, Lai JH. Monosodium urate crystals induced ICAM-1 expression and cell-cell adhesion in renal mesangial cells: Implications for the pathogenesis of gouty nephropathy. J Microbiol Immunol Infect. 2020 Feb;53(1):23-32. doi: 10.1016/j.jmii.2017.12.004. Epub 2018 Jan 31.
14. Khanna P, Johnson RJ, Marder B, LaMoreaux B, Kumar A. Systemic Urate Deposition: An Unrecognized Complication of Gout? J Clin Med. 2020 Oct 3;9(10):3204. doi: 10.3390/jcm9103204.
15. LaMoreaux B, Chandrasekaran V. Gout causing urate cardiac vegetations: summary of published cases. Ann Rheum Dis. 2019;78(Suppl 2):1906. doi: 10.1136/annrheumdis-2019-eular.115.
16. Gasparyan AY, Ayvazyan L, Blackmore H, Kitas GD. Writing a narrative biomedical review: considerations for authors, peer reviewers, and editors. Rheumatol Int. 2011 Nov;31(11):1409-17. doi: 10.1007/s00296-011-1999-3.
17. Coupland S. Gouty concretions on the aortic valves. Trans Pathol Soc Lond. 1873;24:69.
18. Bunim JJ, McEwen C. Tophus of the mitral valve in gout. Arch Pathol. 1940;29:700.
19. Dennstedt FE, Weilbaecher DG. Tophaceous mitral valve: Report of a case. Am J Surg Pathol. 1982 Jan;6(1):79-81.
20. Jaworski RC, Gibson M. Tophaceous aortic valve: a case report. Pathology.1983 Apr;15(2):197-9. doi: 10.3109/00313028309084713.
21. Curtiss EI, Miller TR, Shapiro LS. Pulmonic regurgitation due to valvular tophi. Circulation. 1983 Mar;67(3):699-701. doi: 10.1161/01.cir.67.3.699.
22. Scalapino JN, Edwards WD, Steckelberg JM, Wooten RS, Callahan JA, Ginsburg WW. Mitral stenosis associated with valvular tophi. Mayo Clin Proc. 1984 Jul;59(7):509-12. doi: 10.1016/s0025-6196(12)60443-1.
23. Gawoski JM, Balogh K, Landis WJ. Aortic valvular tophus: identification by X-ray diffraction of urate and calcium phosphates. J Clin Pathol. 1985 Aug;38(8):873-6. doi: 10.1136/jcp.38.8.873.
24. Iacobellis G, A rare and asymptomatic case of mitral valve tophus associated with severe gouty tophaceous arthritis. J Endocrinol Invest. 2004 Nov;27(10):965-6. doi: 10.1007/BF03347542.
25. Koffi B, Guillaudeau A, Sekkal S, Paraf F, Labrousse F, Weinbreck N. Une lésion valvulaire cardiaque inhabituelle [An unusual valvular heart lesion]. Ann Pathol. 2010 Feb;30(1):40-2. French. doi: 10.1016/j.annpat.2009.09.012.
26. Rohani A, Chamania zade P, Ramezani J. A case of mitral valve tophus in a patient with severe gout tophaceous arthritis. J Clin Imaging Sci. 2012;2:68. doi: 10.4103/2156-7514.103058.
27. Klauser AS, Halpern EJ, Strobl S, Gruber J, Feuchtner G, Bellmann-Weiler R, Weiss G, Stofferin H, Jaschke W. Dual-Energy Computed Tomography Detection of Cardiovascular Monosodium Urate Deposits in Patients With Gout. JAMA Cardiol. 2019 Oct 1;4(10):1019-1028. doi: 10.1001/jamacardio.2019.3201.
28. Fukuda T, Subramanian M, Noda K, Kumeta S, Mori H, Ikeda N, Ojiri H. The comprehensive role of dual-energy CT in gout as an advanced diagnostic innovation. Skeletal Radiol. 2025 Nov;54(11):2253-2263. doi: 10.1007/s00256-024-04856-4.
29. Ogdie A, Taylor WJ, Weatherall M, Fransen J, Jansen TL, Neogi T, Schumacher HR, Dalbeth N. Imaging modalities for the classification of gout: systematic literature review and meta-analysis. Ann Rheum Dis. 2015 Oct;74(10):1868-74. doi: 10.1136/annrheumdis-2014-205431.
30. Baffour FI, Ferrero A, Aird GA, Powell GM, Adkins MC, Bekele DI, Johnson MP, Fletcher JG, Glazebrook KN. Evolving Role of Dual-Energy CT in the Clinical Workup of Gout: A Retrospective Study. AJR Am J Roentgenol. 2022 Jun;218(6):1041-1050. doi: 10.2214/AJR.21.27139. Epub 2022 Jan 26. PMID: 35080455.
31. Dalbeth N, Gosling AL, Gaffo A, Abhishek A. Gout. Lancet. 2021 May 15;397(10287):1843-1855. doi: 10.1016/S0140-6736(21)00569-9. Epub 2021 Mar 30. Erratum in: Lancet. 2021 May 15;397(10287):1808. doi: 10.1016/S0140-6736(21)01010-2.
32. Yang L, Wang Z, Yao Z, Cui LG. The Evolving Role of Musculoskeletal Ultrasound in Gout: From Diagnosis to Management-A Narrative Review. J Ultrasound Med. 2026 Feb 6. doi: 10.1002/jum.70195.
33. McCollough CH, Boedeker K, Cody D, Duan X, Flohr T, Halliburton SS, Hsieh J, Layman RR, Pelc NJ. Principles and applications of multienergy CT: Report of AAPM Task Group 291. Med Phys. 2020 Jul;47(7):e881-e912. doi: 10.1002/mp.14157. Epub 2020 May 28. Erratum in: Med Phys. 2021 May;48(5):2694. doi: 10.1002/mp.14614.
34. Araujo EG, Manger B, Perez-Ruiz F, Thiele RG. Imaging of gout: New tools and biomarkers? Best Pract Res Clin Rheumatol. 2016 Aug;30(4):638-652. doi: 10.1016/j.berh.2016.10.010.
35. Girish G, Glazebrook KN, Jacobson JA. Advanced imaging in gout. AJR Am J Roentgenol. 2013 Sep;201(3):515-25. doi: 10.2214/AJR.13.10776.
36. Gerster JC, Landry M, Dufresne L, Meuwly JY. Imaging of tophaceous gout: computed tomography provides specific images compared with magnetic resonance imaging and ultrasonography. Ann Rheum Dis. 2002 Jan;61(1):52-4. doi: 10.1136/ard.61.1.52.
37. Dalbeth N, Doyle A, McQueen FM. Imaging in gout: insights into the pathological features of disease. Curr Opin Rheumatol. 2012 Mar;24(2):132-8. doi: 10.1097/BOR.0b013e32834ff5b1.
38. Schmolke SA, Diekhoff T, Mews J, Khayata K, Kotlyarov M. Deep learning reconstruction enhances tophus detection in a dual-energy CT phantom study. Sci Rep. 2025 May 28;15(1):18687. doi: 10.1038/s41598-025-03012-9.
39. Borghi C, Agabiti-Rosei E, Johnson RJ, Kielstein JT, Lurbe E, Mancia G, Redon J, Stack AG, Tsioufis KP. Hyperuricaemia and gout in cardiovascular, metabolic and kidney disease. Eur J Intern Med. 2020 Oct;80:1-11. doi: 10.1016/j.ejim.2020.07.006.
40. Nishizawa H, Maeda N, Shimomura I. Impact of hyperuricemia on chronic kidney disease and atherosclerotic cardiovascular disease. Hypertens Res. 2022 Apr;45(4):635-640. doi: 10.1038/s41440-021-00840-w.
41. Sharaf El Din UAA, Salem MM, Abdulazim DO. Uric acid in the pathogenesis of metabolic, renal, and cardiovascular diseases: A review. J Adv Res. 2017 Sep;8(5):537-548. doi: 10.1016/j.jare.2016.11.004.
42. Yu W, Cheng JD. Uric Acid and Cardiovascular Disease: An Update From Molecular Mechanism to Clinical Perspective. Front Pharmacol. 2020 Nov 16;11:582680. doi: 10.3389/fphar.2020.582680.
43. Richette P, Perez-Ruiz F, Doherty M, Jansen TL, Nuki G, Pascual E, Punzi L, So AK, Bardin T. Improving cardiovascular and renal outcomes in gout: what should we target? Nat Rev Rheumatol. 2014 Nov;10(11):654-61. doi: 10.1038/nrrheum.2014.124.
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Copyright (c) 2026 Bogdan Penev, Georgi Stoitsev, Prof. Vassil Gegouskov (Author)