Female HCM patients with obstructive physiology undergo myectomy later and have worse diastolic dysfunction but more compliant titin
Contributor: Nick Hawkes
Hypertrophic Cardiomyopathy (HCM) is a genetic condition characterized by unexplained left ventricular hypertrophy often with a wall thickness of greater than or equal to 15mm. it often disproportionately affects the septum and can lead to development of left ventricular outflow obstruction (LVOTO). Myectomy is a targeted surgical reduction in LV mass — thereby reducing LVOTO. Nijenkamp et al analyzed samples obtained during myectomy as well as pre-myectomy echocardiographic markers of diastolic dysfunction in 71 HCM patients. The authors also compared control myocardium to HCM. In this study, female HCM patients presented later, had a higher degree of diastolic dysfunction, a higher amount of fibrosis, more compliant titin, and greater septal thickness when indexed to body surface area (IVSi) compared to males.
Contributor: Nick Hawkes
Sacubitril/valsartan reduces morbidity and mortality in patients with HFrEF, so why has the adoption of this therapy in the outpatient setting been so slow?
Clinical and In Vitro Evidence that LVAD-Induced Von Willebrand Factor Degradation May Alter Angiogenesis
Contributor: Darien Allen
GI bleeds in continuous-flow left ventricular assist device (CF-LVAD) patients are an increasing problem. Bartoli et al posit a two-hit hypothesis to explain the increased risk of mucosal bleeds in this population:
Hit 1: CF-LVAD-induced shear stress activates von Willebrand factor (VWF) multimers leading to enzymatic and mechanical degradation into variably sized fragments and acquired VWF deficiency. CF-LVAD induced VWF deficiency reduces VWF-collagen and VWF-platelet binding resulting in increased risk of mucosal bleeding.
Hit 2: Higher circulating concentrations of VWF fragments lead to altered angiogenesis and likely contribute to the development of angiodysplasia.
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.