Do PDE9A inhibitors improve diastolic dysfunction and myocardial hypertrophy in laboratory models of HFpEF?
PDE9A inhibitors show preclinical promise for reversing diastolic dysfunction and myocardial hypertrophy in HFpEF, but conflicting data necessitate further research before human trials.
INTRODUCTION: There are currently limited effective treatments available to improve lusitropy in patients suffering from heart failure with preserved ejection fraction. The role of PDE9A in diastolic dysfunction has been well-studied over recent years, with a special focus on its association with myocardial hypertrophy. Recent insights into PDE9A inhibition have brought to light the potential for reversal of cardiac remodeling, with multiple studies showing promising results in preclinical data. AREAS COVERED: This expert opinion provides an overview of the role of PDE9A in diastolic heart dysfunction along with the efficacy of PDE9A inhibitors in laboratory models of heart failure with preserved ejection fraction. EXPERT OPINION: The available data on PDE9A inhibition in preclinical studies suggest that there is potential for reversal of diastolic dysfunction and myocardial hypertrophy, however, conflicting data suggests that further studies are required before progressing to clinical trials.
Foroshani et al. (Sat,) studied this question.