Prognostic role of genetic variants in recurrent pericarditis

Abstract

Background

Recent interest in the genetic basis of pericarditis has prompted investigation into the prognostic relevance of disease-associated genetic variants (DAVs), particularly in recurrent pericarditis (RP). Autoinflammatory mechanisms have been implicated in RP, suggesting that genetic predisposition may influence disease severity, treatment response, and long-term outcomes. This study aimed to evaluate the prognostic impact of DAVs in adults with RP.

Methods

A prospective observational cohort study was conducted at a tertiary referral centre for pericardial diseases, enrolling all consecutive adult patients with at least three RP episodes between October 2017 and December 2021. Whole exome sequencing was used to identify DAVs.

Results

Of the 131 patients included, 30 (22.9 %) were found to carry a DAV. Compared with those without DAVs, these patients more frequently exhibited systemic inflammatory features, including elevated C-reactive protein (>10 mg/L in 93.3 % vs 77.7 %, p = 0.049) and fever (76.7 % vs 49.5 %, p = 0.008). After a median follow-up of 47 months (IQR 34–75), long-term remission was achieved in only 33.3 % of DAV carriers, compared to 67.3 % in the control group (log-rank p = 0.03). In multivariable Cox regression analysis, the presence of a DAV remained independently associated with a reduced likelihood of achieving sustained remission (HR 0.468, 95 % CI 0.240–0.984; p = 0.045).

Conclusions

This is the first study to assess outcomes in RP patients with DAVs. Approximately one in four patients showed a genetic predisposition, which was linked to a larger inflammatory burden and a significantly lower probability of long-term remission, highlighting the prognostic value of genetic testing in RP.