Background: Patients with rheumatoid arthritis face an elevated risk of developing heart failure (HF), but the cardiac prerequisites and disease mechanisms are unknown.

Objectives: This study employed experimental models of chronic arthritis and HF to explore the cardiac effects of arthritis-induced chronic inflammation on HF development.

Methods: Rheumatoid arthritis-like phenotype was induced by delayed-type hypersensitivity arthritis (DTHA) in male BALB/c mice (n=29). Control mice received vehicle injections (n=29). The DTHA protocol includes 1) immunization towards methylated bovine serum albumin (mBSA) 2) intravenous injection of mixed anti-collagen II antibodies, and finally 3) release of local arthritis by hind-leg subcutaneous mBSA injection. Three days after induction of arthritis, the mice in both the DTHA group and controls were randomized to HF surgery (n=16 in both groups) or sham surgery (n=13 in both groups). HF was induced via thoracotomy and placement of a constricting o-ring around the ascending aorta. Step 2 and 3 of the DTHA protocol were repeated weekly for 8 consecutive weeks to uphold inflammation. Cardiac magnetic resonance imaging (MRI) was performed 12 and 54 days after surgery, with subsequent euthanization and harvesting of blood and tissue.

Results: We found evidence of fluctuating, yet sustained local and systemic inflammation after induction of experimental arthritis, and clear development of HF after surgery. Mice with both arthritis and HF exhibited significantly increased mortality compared to the HF group without arthritis (p=0.04). Increased levels of brain natriuretic peptide (BNP) in cardiac tissue (p=0.03), suggests worsening of HF as cause of this observation. However, no significant functional differences were detected on cardiac MRI.

Conclusion: Chronic systemic inflammation mediated by limb-restricted arthritis increased mortality in mice with HF induced by aortic constriction. Even though statistically significant increments of BNP were found, the cause of observed increased mortality remains elusive, as no functional differences could be found on MRI.

REFERENCES: NIL.

Acknowledgements: The authors wish to thank Merete Høyem for expert technical assistance.

Disclosure of Interests: None declared.