American Heart Association

sGC activator

VITALITY-HFpEF: Designed to test the hypothesis that vericiguat may improve physical functioning in patients with HFpEF

Contributor: Emily Cendrowski

VITALITY-HFPEF is a trial underway which will evaluate the efficacy of vericiguat in HFpEF patients by using the KCCQ-PLS (Kansas City Cardiomyopathy Questionnaire Physical Limitation Score) as a primary endpoint. The choice of this primary endpoint will make it the first HF trial utilizing a quality of life, patient-reported outcome (PRO) as a primary endpoint. There remains a need for medications which improve mortality and functional status for patients with HFpEF. An ongoing area of research involves the cyclic guanosine monophosphate (cGMP) pathway.

Oxidative state of cGMP-dependent protein kinase determines the efficacy of sildenafil vs direct guanylate cyclase activators in pressure-overload HF

Contributor: Elise Vo

Precision therapy for HF is on the horizon. Activating cyclic guanosine monophosphate (cGMP)-dependent protein kinase-1α (PKG1α), results in vasodilation and prevents cardiac remodeling — a good thing. There are two ways to activate PKG1a: 1) directly soluble guanylate cyclase (sGC) activators and 2) indirectly by PDE5 inhibition. So, do these two methods of targeting PKG1α work equally well? Nakamura et al used a TAC murine model to demonstrate that the oxidative state of PKG1α determines whether or not sildenafil is efficacious in preventing pathologic remodeling in pressure-overload HF.