Abstract 16961: A Novel Large Animal Model of Chronic Kidney Disease-induced Heart Failure With Preserved Ejection Fraction (HFpEF)
Introduction: Large animal models are invaluable to gain a better understanding of the complexity of HFpEF and current small animal models are not representative of the syndrome in patients. HFpEF accounts for approximately 50% of heart failure cases, but evidence-based therapies are lacking that improve morbidity and mortality in this syndrome. Porcine cardiac and renal anatomy and physiology are comparable to that of humans, making them suitable for cardiovascular research.
Hypothesis: We hypothesized that a chronic kidney disease (CKD) model produces the corresponding cardiac changes of an HFpEF model.
Methods: Yorkshires pigs (n=20) underwent 5/6 nephrectomy via renal artery embolization using PVA particles and ethanol. At baseline and 4 weeks post embolization, glomerular filtration rate (GFR), creatinine, BUN, proteinuria, renal and cardiac MRI, and pressure volume loops (PV loops) were obtained.
Results: The CKD model was confirmed by an increase in creatinine from baseline of 1.29 ± 0.041 to 4 weeks post embolization of 2.29 ± 0.157 (p<0.0001), increase in BUN (Δ13.50 mg/dl± 2.99mg/dl; p=0.0003), and protein/creatinine ratio (Δ0.311mg/g; p=0.018), and decrease in GFR (Δ49.82 ± 6.41 ml/min; p=0.0002). Blood pressure was not different between baseline and 4 weeks post embolization (p=0.7). Left ventricular (LV) mass increased by 20.3% (p= 0.0001). Correction of variability in LV mass by body surface area showed an increased of 17.49% (p=0.001). Wall thickening (maximal end-diastolic wall thickness) occurred preferentially in the posterior, anteroseptal, and posteroseptal walls (p<0.008). There was an increase in end diastolic pressure (p=0.01), end diastolic pressure volume relationship (p=0.005), end systolic pressure volume relationship (p=0.05), and arterial elastance (p=0.03), without a change in ejection fraction. Diffuse intramyocardial fibrosis was evident, assessed by histological analysis and delayed enhancement MRI imaging.
Conclusions: A CKD large animal model manifests the characteristics of HFpEF, including an increase in LV mass, wall thickening, fibrosis, and LV and arterial stiffness, but without hypertension. This model is a useful tool for investigating the pathophysiology of cardiac remodeling in HFpEF.
Author Disclosures: A.M. Castellanos: None. B.A. Tompkins: None. V. Florea: None. M. Natsumeda: None. K. Collon: None. J. Rodriguez: None. M. Rosado: None. W. Balkan: None. J.M. Hare: Other; Significant; Dr. Hare reported having a patent for cardiac cell-based therapy., He holds equity in Vestion and maintains a professional relationship with Vestion as a consultant and member of the Board of Directors and Scientific Advisory Board. I.H. Schulman: None.
- © 2016 by American Heart Association, Inc.