Genetic variants in patients with recurrent pericarditis.

Aims: Presence of family cases and multiple recurrences of pericarditis suggest the existence of a possible genetic background in at least 10% of cases. The aim of the present study is to describe the genetic landscape of a cohort of patients with multiple recurrences (at least two recurrences).

Methods: Retrospective cohort study of consecutive adult patients referred for at least two episodes of recurrences in a tertiary referral centre. Genetic testing was performed by whole exome sequencing (WES).

Results: Our cohort included 108 consecutive patients with recurrent pericarditis [median age 32 years, interquartile range (IQR) 18.5; 67.6% females, all Caucasian, idiopathic aetiology in 71.1%] with a median number of recurrences of 5 (IQR 2). Overall, 16 patients (14.8%) had variants in genes related to the inflammatory response. Eleven variants were located in genes already associated with recurrent pericarditis (NLRP3, TNFRSF1A and MEFV) and five in inflammation/immunodeficiency-related genes (IFIH1, NFKBIA, JAK1, NOD2 and ALPK1). Furthermore, we identified 10 patients with variants located in genes associated with conduction system-related diseases, and 22 variants in 21 patients with genes associated with heart structural-related diseases.

Conclusion: In this first observational study using WES to assess genetic variants in patients with multiple recurrences of pericarditis, about 15% of patients bore at least one variant that may be related to the disease. These findings highlight the importance of addressing the role of genetic predisposition in recurrent pericarditis. Moreover, 28.7% of patients carry variants in different cardiac genes, worthy of a deeper investigation.