Abstract

Summary

To study the levels of inflammatory biomarkers in patients with rheumatic heart disease (RHD) and to assess their association with permanent atrial fibrillation (AF).
 

Materials and Methods

The study included 102 patients with a verified diagnosis of RHD. Patients were divided into two groups: (1) with sinus rhythm (n=54) and (2) with permanent AF (n=48). All patients underwent clinical examination, echocardiography, laboratory tests, and determination of inflammatory biomarkers–high-sensitivity C-reactive protein (hs-CRP) and interleukin-6 (IL-6). Statistical analysis included descriptive statistics, Mann-Whitney U test, χ² test, and Spearman correlation analysis.
 

Results

Patients with permanent AF were older (median age 55.0 vs. 38.0 years; p<0.001), had a longer history of RHD (20 years vs. 9 years; p<0.001), and presented with more severe heart failure (NYHA class III-IV: 79.2% vs. 40.7%; p<0.001). They demonstrated significant left atrial dilation (5.6 cm vs. 4.8 cm; p<0.001) and reduced left ventricular ejection fraction (50% vs. 55%; p=0.003). Inflammatory biomarker concentrations were significantly higher in the AF group: hs-CRP 6.1 [4.8; 8.2] mg/L vs. 2.4 [1.5; 3.8] mg/L, and IL-6 5.0 [3.5; 7.1] pg/mL vs. 1.2 [0.6; 2.1] pg/mL (p<0.001). Correlation analysis revealed significant associations of hs-CRP and IL-6 levels with NYHA class (rₛ=0.58 and rₛ=0.65), left atrial diameter (rₛ=0.52 and rₛ=0.46), and systolic pulmonary artery pressure (rₛ=0.48 and rₛ=0.40) in AF patients (p<0.01). After Bonferroni correction for multiple comparisons, significant correlations in the AF group persisted for hs-CRP with left atrial diameter and NYHA class, and for IL-6 with age and NYHA class. In the sinus rhythm group, no correlation remained statistically significant after correction.
 

Conclusion

Permanent AF in patients with RHD is associated with elevated hs-CRP and IL-6 levels, confirming the important role of chronic inflammation in disease pathogenesis. The findings demonstrate a close relationship between biomarkers, clinical severity, and structural-functional cardiac remodeling, highlighting their potential for risk stratification and dynamic patient monitoring.
 

Keywords

rheumatic heart disease (RHD) atrial fibrillation (AF) inflammation high-sensitivity C-reactive protein (hs-CRP) interleukin-6 (IL-6).

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References

  1. 1. Kurashin V.K., Borovkova N.Yu., Borovkov N.N., Kurashina V.A., Bakka T.E. Kliniko-patogeneticheskaya kharakteristika i taktika vedeniya bol’nykh s fibrillyatsiei predserdii v statsionare terapevticheskoi kardiologii na sovremennom etape [Clinical and pathogenetic characteristics and management tactics of patients with atrial fibrillation in the therapeutic cardiology hospital at the present stage]. Kardiovaskulyarnaya terapiya i profilaktika. 2020;19(3):2488.
  2. 2. Shenthar J. Management of atrial fibrillation in rheumatic heart disease. Heart Rhythm O2. 2022 Dec 16;3(6Part B):752-759. doi: 10.1016/j.hroo.2022.09.020
  3. 3. Sharma G., Ghati N., Sharique M., Sharma S., Shetkar S., Karmakar S., et al. Role of inflammation in initiation and maintenance of atrial fibrillation in rheumatic mitral stenosis – An analytical cross-sectional study. J Arrhythm. 2020;36(6):1007-1015. [https://doi.org/10.1002/joa3.12428](https://doi.org/10.1002/joa3.12428)
  4. 4. Kurbonova F.U., Shukurova S.M., Radzhabov R.M., Radzhabova G.M. Prediktory neblagopriyatnogo prognoza revmaticheskikh porokov serdtsa [Predictors of unfavorable prognosis of rheumatic heart disease]. Vestnik poslediplomnogo obrazovaniya v sfere zdravookhraneniya. 2020;(2):32-39.
  5. 5. Pang Z., Ren Y., Yao Z. Interactions between atrial fibrosis and inflammation in atrial fibrillation. Front Cardiovasc Med. 2025;12:1578148. [https://doi.org/10.3389/fcvm.2025.1578148](https://doi.org/10.3389/fcvm.2025.1578148)
  6. 6. Nso N., Bookani K.R., Metzl M., Radparvar F. Role of inflammation in atrial fibrillation: A comprehensive review of current knowledge. J Arrhythm. 2020;37(1):1-10. [https://doi.org/10.1002/joa3.12473](https://doi.org/10.1002/joa3.12473)
  7. 7. Basieva M.A., Talibova S.M., Kazanova P.V., Avanesyan G.A., Zhigunova O.V., Ispiryan A.Yu., et al. Assotsiatsiya urovnei biomarkerov sistemnogo vospaleniya s klinicheskimi parametrami u patsientov s fibrillyatsiei predserdii [Association of systemic inflammation biomarkers with clinical parameters in patients with atrial fibrillation]. Annaly aritmologii. 2024;21(4):245-254. [https://doi.org/10.15275/annaritmol.2024.4.5](https://doi.org/10.15275/annaritmol.2024.4.5)
  8. 8. Kurbonova F.U., Shukurova S.M., Radzhabova G.M. Kompleksnaya otsenka revmaticheskikh porokov serdtsa na statsionarnom etape [Comprehensive assessment of rheumatic heart disease at the hospital stage]. Vestnik Akademii meditsinskikh nauk Tadzhikistana. 2019;9(4):380-386. [https://doi.org/10.31712/2221-7355-2019-9-4-380-386](https://doi.org/10.31712/2221-7355-2019-9-4-380-386)
  9. 9. Yousef A.M., Rifaie O.A., Hamza M.A., Amin S.A. Study of the relation between serum levels of long-acting penicillin and the inflammatory markers: C-reactive protein and interleukin-6 in patients with chronic rheumatic heart disease. Egypt Heart J. 2021;73(1):19. [https://doi.org/10.1186/s43044-021-00141-0](https://doi.org/10.1186/s43044-021-00141-0)
  10. 10. Kumar S., Chand Negi P., Asotra S., Chandel M., Kumar J., Merwah R., et al. Inflammatory cytokine levels in rheumatic heart disease and their association with use of benzathine penicillin: A case-control pilot study. Indian Heart J. 2025;77(2):59-62. [https://doi.org/10.1016/j.ihj.2025.01.007](https://doi.org/10.1016/j.ihj.2025.01.007)
  11. 11. Wang Z., Wang B.H., Yang X.L., Xia Y.L., Zhang S.M., Che Y. Relationship of inflammatory indices with left atrial appendage thrombus or spontaneous echo contrast in patients with atrial fibrillation. World J Clin Cases. 2024;12(21):4550–4557. [https://doi.org/10.12998/wjcc.v12.i21.4550](https://doi.org/10.12998/wjcc.v12.i21.4550)
  12. 12. Asrial A.A., Reviono R., Soetrisno S., Setianto B.Y., Widyaningsih V., Nurwati I. et al. Correlation between circulating fibrosis biomarkers with left atrial function and left atrial volume index in rheumatic mitral stenosis. Narra J. 2024;4(1):e293. [https://doi.org/10.52225/narra.v4i1.293](https://doi.org/10.52225/narra.v4i1.293)
  13. 13. Zhang Y., Ni X. Prognostic value of nine inflammatory biomarkers for critically ill patients with rheumatic heart disease: a retrospective study. Front Immunol. 2025;16:1610967. [https://doi.org/10.3389/fimmu.2025.1610967](https://www.google.com/search?q=https%3A%2F%2Fdoi.org%2F10.3389%2Ffimmu.2025.1610967)
  14. 14. Chen X., Zhang X., Fang X., Feng S. Association of inflammatory markers with clinical outcomes in atrial fibrillation: a meta-analysis. Front Cardiovasc Med. 2025;12:1504163. [https://doi.org/10.3389/fcvm.2025.1504163](https://www.google.com/search?q=https%3A%2F%2Fdoi.org%2F10.3389%2Ffcvm.2025.1504163)