Targeting heart failure with preserved ejection fraction in settings of arthritis (non-clinical)

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Rheumatoid arthritis (RA) patients have a high rate of cardiovascular disease as a group, with cardiovascular events causing around half of all deaths, and people with RA twice as likely to develop heart problems as compared to the general population. They are particularly susceptible to a type of heart failure known as heart failure with preserved ejection fraction (HFpEF); it is accompanied by diastolic dysfunction, whereby the heart fails to relax and refill fully after each heartbeat. What causes this dysfunction in RA patients is unknown and current medicines do not reduce these heart problems. Dr Chen and her team have developed an experimental model of arthritis, which mirrors the specific heart dysfunction of RA patients and plan to use this to uncover novel therapies.

Using a laboratory model of arthritis, the team can explore the timelines of how heart problems develop in RA. This will allow them to establish whether certain white blood cells contribute to heart inflammation and development of the diastolic dysfunction. A novel therapy that limits the movement of these inflammatory cells from the blood to the heart will subsequently be tested. They will also use the model to test an existing therapy for RA patients, known as anti-interleukin-b and its effect on heart function and joint symptoms will be assessed.

By studying the association between white blood cells in the bloodstream and development of heart problems in RA patients, the team hopes to identify predictors of heart problems to guide early intervention, as well as identify novel targets for drugs and therapies. Clarifying whether targeting inflammation in this patient group is beneficial may ultimately impact decision making for preventing development of heart failure in RA patients and/or developing tailored treatments for patients who have already developed heart problems. Successful reduction of heart dysfunction in RA patients will not only reduce death but will also improve their quality of life. In terms of benefits for the wider clinical community, it is indicated that there is a link between diseases associated with inflammation (obesity, diabetes mellitus, chronic kidney disease and inflammatory arthritis) and development of HFpEF but unfortunately, the long-term prognosis for HFpEF patients remains poor. Findings from this project will increase our knowledge on mechanisms that connect inflammation to heart failure and may provide new targets for therapeutic intervention.