Abstract
Abstract Background: Chronic heart disease imposes a significant disease burden to society. Of patients diagnosed with heart failure, 30-40% die within one year. Even with the advent of new treatments mortality decreased only by 10% absolute risk reduction between 1995 and 2005. Objective: The aim of this project thesis is to explore a potential role for PDE1 as a mediator of cardiac pathology and as target for future pharmacological therapy of cardiac disease based on the available literature. Method: A systematic literature searche in PubMed performed during Q1 2017. Eight search terms was applied in PubMed, and three predefined inclusion criteria was used to evaluate whether each article should be included for further analysis in this project thesis. Results: The systematic literature search identified a total of 68 publications, and of these 20 were included based on the predefined inclusion criteria. Based on the included publications, the role of PDE1 as possible future treatment target was analyzed for cardiac hypertrophy and heart failure, pulmonary hypertension and arterial hypertension. For these three disease categories, experimental evidence from preclinical models was available. These were consistent with beneficial effects for PDE1 inhibition in cardiac hypertrophy, heart failure and pulmonary hypertension. The role of PDE1 inhibition in arterial hypertension was little studied, and little or no literature was available for the effect of PDE1 inhibition in other cardiac diseases. Conclusion: Existing evidence hints at a potential for a future role of PDE1 inhibition in management of cardiac hypertrophy and cardiac failure as well as pulmonary hypertension.