American Heart Association

Chris Sobowale

Not necessary to adjust NT-proBNP thresholds for HFrEF patients with atrial fibrillation

Contributor: Chris Sobowale

Heart failure patients with HFrEF and atrial fibrillation (HFrEF-AF) have higher NT-proBNP than HFrEF patients without atrial fibrillation (AF). This is thought to be a consequence of AF and not necessarily correlated with deleterious clinical outcomes.

HF clinical trials have stipulated different inclusion NT-proBNP levels for patients with HFrEF-AF. It turns out, a defined higher NT-proBNP level for patients with HFpEF-AF may not be necessary.

Increasing ketone body metabolism reduces cardiac dysfunction in a murine model of pressure-overload-induced heart failure

Contributor: Chris Sobowale

In a mouse model of pressure overload-induced heart failure, D-beta-hydroxybutyrate dehydrogenase I (Bdh1), an enzyme that catalyzes the interconversion of two major ketone bodies produced during fatty acid catabolism (acetoacetate and beta-hydroxybutyrate) is upregulated and increases ketone-body oxidation rate, i.e ketone body metabolism (KBM). Uchihashi et al generated cardiac-specific Bdh1-overexpressing mice to determine the role of ketone-body metabolism in the myocardium. They demonstrate that overexpression of Bdh1 resulted in increased ketone body utilization, resistance to pathologic cardiac remodeling, and a reduction in reactive oxygen species generation.

Ketone bodies are generated from Acetyl-CoA stemming from fatty acid metabolism in the liver. Ketones are then oxidized back to Acetyl-CoA in various tissues to provide energy. Interestingly, Beta-hydroxybutyrate (a component of ketone bodies) decreases ischemic reperfusion injury in rat hearts and decreases oxidative stress by inhibiting histone deacetylases (HDACs) and upregulating antioxidant genes. The less HDACs, the more histone acetylation, and the less oxidative stress.

Bhd1-overexpressing transgenic (Bdh1 Tg) mice were made by injecting Bdh1 cDNA into mouse embryos. All Bdh1 Tg and wild type (WT) mice then underwent a left thoracotomy. Half of the mice had traverse aortic constriction (TAC) by ligation of the transverse thoracic aorta to cause pressure overload-induced heart failure. The other half (sham group) had no ligation. Bdh1 levels were measured using proteomics and DNA microarray, and were further confirmed by PCR and Western Blot. The ketone body oxidation rate (KBM) was evaluated by measuring 14CO2 isotope levels 8 weeks after TAC.

At baseline, Bdh1 Tg mice had a significant increase in Bhd1 protein levels (2.5 fold) and KBM (1.7 fold) when compared to WT mice (p<0.05). TAC caused a significant increase in Bhd1 expression (2.8 fold higher in Bdh1 Tg mice) (p<0.05). Overall, the TAC Bdh1 Tg mice had a significant increase in KBM compared to TAC WT mice (p<0.05) (Figure 2A).

TAC caused enlargement of the LVEDd and reduction in EF. TAC operated Bdh1 Tg mice had less LV dilation and significantly less cardiac dysfunction compared to WT mice (p<0.05). The area of fibrosis after TAC was significantly decreased in Bdh1 Tg mice. Immunostaining revealed that reactive oxygen species (ROS) were induced by TAC but significantly reduced in TAC Bhd1 Tg mice compared to TAC WT mice (p<0.05). Also, gene expression of superoxide dismutase, an antioxidant was upregulated in TAC Bdh1 Tg mice.

No study is perfect. There were no hemodynamic data provided and it is unclear how working heart models will correlate with the Langendorff heart model used in this study.

In a heartbeat… Failing hearts depend on ketone bodies as fuel and increasing ketone-body utilization has potential to decrease cardiac dysfunction and ameliorate oxidative stress.

Study Link: Cardiac-Specific Bdh1 Overexpression Ameliorates Oxidative Stress and Cardiac Remodeling in Pressure Overload–Induced Heart Failure

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)

Decreased incidence yet increased prevalence of heart failure among Medicare beneficiaries

Contributor: Chris Sobowale

Over 6.5 million Americans have HF, costing over $31 billion annually. Those are big numbers, but what is the trend? Berry et al explored the epidemiology of heart failure by examining fee-for-service Medicare patients from 2002-2013. This was presented as a late-breaker at the AHA Scientific Sessions 2017 with simultaneous publication in Circulation: Heart Failure – the new editor teams’ first simultaneous publication – but hopefully not our last!

Watch out for heart failure in patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia

Contributor: Chris Sobowale

Natural history is catching up when arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) patients develop heart failure.

ARVC/D is an inherited cardiomyopathy in which myocardium is replaced with fibro-fatty tissue.  This is followed by development of right ventricular dysfunction and ventricular arrhythmia.

Why are heart failure specialists seeing more patients with ARVC/D? The patients are living longer. Increased awareness allows timely diagnosis. ICD implantation prevents sudden cardiac death. As a result, ARVC/D patients eventually develop heart failure. Gilotra et al explores the increased prevalence of HF related to ARVC/D and characterizes the evolution to HF.