Phosphodiesterase (PDE) 3A mutations cause hypertension with brachydactyly (HTNB). While the brachydactyly (short fingers) is harmless, the hypertension is severe and would typically lead to end-organ damage, such as cardiac hypertrophy, heart failure or chronic kidney disease. Surprisingly, HTNB patients do not show any significant damage of this kind. 
The mutations cause activation of PDE3A enzymes. Thus, the goal of the project is the identification of small molecule PDE3A activators to mimic the beneficial effects of the mutations for protection of the heart from hypertension-induced injury. Eventually, the scientists aim to introduce the selective and long-term activation of PDE3A rather than short-term non-selective PDE3 inhibition that is currently used for cardioprotection.
 

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