Detecting sub-clinical disease activity in patients with chronic rheumatic valvular heart disease

Abstract

Objective

Valve disease progression in rheumatic heart disease(RHD) is generally attributed to recurrent attacks of acute rheumatic fever(ARF). However, persistence of chronic sub-clinical inflammation remains a plausible but unproven cause. Non-invasive means to identify sub-clinical inflammation may facilitate research efforts towards understanding its contribution to disease progression.

Methods

Patients with chronic RHD, without clinical evidence of ARF, undergoing elective valve surgery were enrolled. Sub-clinical inflammation was ascertained by histological evaluation of left atrial appendage and valve tissue excised during surgery. We assessed the diagnostic utility of Gallium-67 scintigraphy imaging, and inflammatory biomarkers, hsCRP, IL-2, IL-6, Tumor Necrosis Factor-Alpha(TNF-α), Interferon-gamma(IFN-γ), and Serum Amyloid A(SAA), in identifying patients with sub-clinical inflammation.

Results

Of the 93 RHD patients enrolled(mean age 34 ± 11 years, 45% females), 86 were included in final analysis. Sub-clinical inflammation was present in 27 patients(31.4%). Patients with dominant regurgitant lesions were more likely to have sub-clinical inflammation compared to those with stenotic lesions, though this association was not statistically significant(dominant regurgitant lesions vs isolated mitral stenosis: OR 3.5, 95%CI 0.68–17.96, p = 0.133). Inflammatory biomarkers were elevated in the majority of patients: hsCRP, IL-2, IL-6, TNF-α, and IFN-γ in 44%, 89%, 90%, 79%, and 81% patients, respectively. However, there was no significant association between biomarker elevation and histologically ascertained sub-clinical inflammation. Ga-67 imaging was unable to identify inflammation in the 15 patients in whom it was performed.

Conclusion

Sub-clinical inflammation is common in RHD patients. Conventional inflammatory markers are elevated in the majority, but aren’t discriminatory enough to identify the presence of histologic inflammation.

Graphical abstract

Correlation of inflammatory biomarkers with histological inflammation. (The green horizontal line represents the proportion of patients who had inflammation on histological examination. The vertical bars represent the proportion of patients in whom the inflammatory markers were elevated. These biomarkers were elevated in a non-discriminatory fashion).