American Heart Association

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.

Old drug… new trick? Treatment with sildenafil may prevent device thrombosis and ischemic stroke in LVAD patients.

Contributor: Chris Sobowale

Bleeding and thrombosis account for almost half of adverse events in patients with CF-LVADs.

Saeed et al analyzed 144 HeartMate II (HMII) CF-LVAD patients in a single center, retrospective study. Patients in the sildenafil groups were on sildenafil for pulmonary hypertension or right ventricular dysfunction for at least 30 days after discharge from CF-LVAD implant. Patients were divided into four groups:

  1. Low level hemolysis not on sildenafil (n=31)
  2. Low level hemolysis on sildenafil (n= 16)
  3. No low level hemolysis not on sildenafil n= (76)
  4. No low level hemolysis on sildenafil (n=21)