THE INVESTIGATION OF HEART RATE REDUCTION FOLLOWING CARDIAC TRANSPLANTATION

Abstract

Introduction: Sinus tachycardia is common after heart transplantation (HTX) due to graft denervation. Given heart rate (HR) reduction is linked to improved clinical outcomes in patients with native cardiovascular disease, the merits of lowering post transplant sinus tachycardia (PTST) warrants further investigation. Tachycardia can cause reversible structural and functional changes within the heart. Inaddition, it can predispose to localised inflammation and immune activation within the transplanted heart, yet to date the effects of HR on inflammatory status remain unknown.Methods: A retrospective analysis was performed to assess any significant association between elevated HR and clinical outcome in long-term survivors of HTX. Subsequently, further investigations were performed including prospective studies, which investigated the relationship between HR reduction (using the drug, Ivabradine) with clinical and immunological outcomes in HTX recipients.Results: No significant association between elevated HR and adverse clinical outcome was found in long-term survivors of HTX. The initial prospective study revealed a significant HR reduction secondary to Ivabradine administration. However, HR reduction did not alter clinical outcome, nor the circulating cytokine environment in this cohort. No significant difference was observed in blood pressure, cardiac function, or the concentration of 19 selected cytokines during the follow-up period.Conclusion: HR reduction did not seem to have any clear effect on the graft function, nor peripheral cytokine profile in this cohort. This raises the hypothetical conclusion that HR reduction per se is unlikely to help modulate immunoactive processes following HTX. Alternatively, the results could raise the possibility that another mechanism plays a significant role.

Date of Award	1 Aug 2015
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Simon Williams (Supervisor) & James Fildes (Supervisor)