Mitral regurgitation as an inflammatory valvular phenotype in heart failure

Background

Valvular heart disease (VHD) frequently coexists with HF. Although inflammation contributes to valvular remodeling, its prognostic interplay with valve disease severity remains unclear.

Purpose

To evaluate the interaction between systemic inflammation and valvular severity among heart failure (HF) patients.

Methods

A retrospective cohort study of HF patients (2009-2025). Mitral regurgitation (MR), tricuspid regurgitation (TR), and aortic stenosis (AS) were graded by standardized echocardiography. Systemic inflammation was assessed by C-reactive protein (CRP) measured within ± 90 days of HF diagnosis, where high CRP was defined as ≥ the third quartile. Patients were categorized by valve severity (mild vs. significant) and CRP level. The primary outcome was all-cause mortality analyzed using multivariable Cox models adjusted for age, sex, inflammatory markers and comorbidities.

Results

Among 14,338 patients (median age 75 years, 60% males), 49% died during a median follow-up of 4.0 years (IQR 1.5-7.5). Mild MR with high CRP was associated with a 16% higher mortality risk (HR 1.16, 95% CI 1.04-1.29, p = 0.005; p-interaction = 0.006) compared to mild MR with low CRP. For significant MR, high CRP was associated with a 42% higher risk (HR 1.42, 95% CI 1.23-1.64, p < 0.001; p-interaction < 0.001) compared to low CRP (Figure). No parallel inflammatory association emerged for TR or AS across any severity strata. Consistent patterns were observed when using ESR and exclusion of antimicrobial use.

Conclusion

Among HF patients, systemic inflammation markedly modifies risk in MR though not in TR or AS, positioning MR as an inflammation-sensitive valvular phenotype.

Figure: Kaplan-Meier survival by MR severity and CRP level: Survival curves compare four prespecified groups based on MR severity and inflammatory status: Mild and low CRP, Mild and high CRP, significant and low CRP and significant and high CRP. High CRP was defined as a value ≥ the valve-specific third quartile (Q3), and Low CRP as < Q3. Survival differences were assessed using the log-rank test.KM by CRP Strata and MR SeverityFor image description, please refer to the figure legend and surrounding text.