Can routine inflammation tests miss hidden inflammation in rheumatic heart disease?

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Progression of valve disease in rheumatic heart disease (RHD) is generally attributed to repeated attacks of acute rheumatic fever (ARF). Persistent chronic sub-clinical inflammation— inflammation without clinical signs—remains a plausible but unproven cause. Non-invasive ways to identify this inflammation could help researchers understand its contribution to disease progression.

This observational diagnostic-utility study enrolled patients with chronic RHD who had no clinical evidence of ARF and were undergoing elective valve surgery. Researchers determined whether sub-clinical inflammation was present by histologically examining left atrial appendage and valve tissue removed during surgery. They assessed whether Gallium-67 scintigraphy and the inflammatory biomarkers hsCRP, IL-2, IL-6, tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), and serum amyloid A (SAA) could identify patients with this inflammation.

Of 93 enrolled RHD patients, whose mean age was 34 ± 11 years and 45% of whom were female, 86 were included in the final analysis. Sub-clinical inflammation was found in 27 patients (31.4%). Patients with predominantly regurgitant valve lesions were more likely to have sub-clinical inflammation than those with stenotic lesions, but the association was not statistically significant: predominantly regurgitant lesions versus isolated mitral stenosis, odds ratio 3.5, 95% confidence interval 0.68–17.96, p = 0.133.

Inflammatory biomarker elevations were frequent: hsCRP, IL-2, IL-6, TNF-α, and IFN-γ were elevated in 44%, 89%, 90%, 79%, and 81% of patients, respectively. However, biomarker elevation was not significantly associated with sub-clinical inflammation established by histology. Gallium-67 imaging did not identify inflammation in any of the 15 patients who underwent it.

The researchers concluded that sub-clinical inflammation is common in RHD patients. Conventional inflammatory markers were elevated in the majority overall, but did not distinguish patients with histologic inflammation well enough to identify its presence.