Heart Failure Research
Basic research in Manchester has identified the importance of several molecules including PMCA4 (Oceandy et al. Circulation 2007), MKK4 (Liu et al. Circ Res 2009), RASSF1A (Oceandy et al. Circulation 2009), and PAK 1 (Liu et al. Circulation 2011), in cardiac hypertrophy and remodelling, both critical processes in the development of heart failure.
Translational studies relating to these molecules are in progress.The first small molecule inhibitor of PMCA4 was identified in Manchester, and it was showed to reduced pathological cardiac hypertophy in an animal model. Due to an unexpected effect on sperm motility, further work has been funded by via a Gates Foundation grant, to explore the contraceptive potential of topical application of the novel compound in clinical studies.
The Greater Manchester CLAHRC heart disease theme (Deaton, Boaden) has used a facilitated model of improvement with over 40 primary care practices, to improve care for patients with heart failure. Every evaluation demonstrates a significant increase in heart failure prevalence and use of evidence based management, including use and up-titration of ACE inhibitors and beta blockers in patients with left ventricular sytolic dysfunction.