American Heart Association

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.

By |November 14th, 2018|cardiomyopathy, Nicholas Hawkes|0 Comments
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Low Adoption Rates of Sacubitril/Valsartan Use in the US

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?

By |November 14th, 2018|Entresto, HFrEF, Nicholas Hawkes, sacubitril/valsartan|0 Comments
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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.

By |November 14th, 2018|GI bleed, LVAD, mechanical circulatory support|0 Comments
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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.

By |September 14th, 2018|Elise Vo, protein kinase G-1 alpha, sGC activator, sildenafil|0 Comments
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Slow Adoption and Low Adherence of Sacubitril/Valsartan for HFrEF

Contributor: Nick Hawkes

PARADIGM – HF demonstrated that Sacubitril/Valsartan reduces morbidity and mortality in patients with HFrEF compared to ACE-I/ARB therapy, so why is its adoption in the real world delayed?

Sangaralingham et al. accessed data from OptumLabs Data Warehouse, a large database of de-identified medical and pharmacy claims. Among patients identified based on systolic HF ICD codes, those prescribed sacubitril/valsartan were compared to those who were not. Patient variables included health plan, age, gender, race, region, comorbidities, other prescription medications, and provider specialty. Additionally the costs, out-of-pocket (OOP) and to the health plan, were captured.

By |September 7th, 2018|ACE-I/ARB, Entresto, HFrEF, Nicholas Hawkes, PARADIGM-HF|0 Comments
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