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Lumped-Parameter and Finite Element Modeling of Heart Failure with Preserved Ejection Fraction
Published on: February 13, 2021
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Reverse electrical remodeling in rats with heart failure and preserved ejection fraction
Jae Hyung Cho1, Peter J Kilfoil1, Rui Zhang1
1Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.
JCI Insight
|October 5, 2018
Summary
Cardiosphere-derived cells (CDCs) reduce ventricular arrhythmias (VAs) in heart failure with preserved ejection fraction (HFpEF) by improving electrical stability and reducing fibrosis. This therapy may contribute to increased survival in HFpEF patients.
Area of Science:
- Cardiology
- Regenerative Medicine
- Electrophysiology
Background:
- Sudden death is a primary cause of mortality in heart failure with preserved ejection fraction (HFpEF).
- Cardiosphere-derived cells (CDCs) have shown potential in reducing inflammation and fibrosis in HFpEF models.
- The anti-arrhythmic effects of CDCs in HFpEF remain largely unexplored.
Purpose of the Study:
- To investigate the hypothesis that CDCs decrease ventricular arrhythmias (VAs) in a rat model of HFpEF.
- To elucidate the mechanisms by which CDCs might suppress arrhythmogenesis.
- To assess the impact of CDC therapy on survival in HFpEF.
Main Methods:
- Induction of HFpEF in Dahl salt-sensitive rats using a high-salt diet.
- Administration of allogeneic rat CDCs or placebo (phosphate-buffered saline) to rats with echo-verified HFpEF.
- Programmed electrical stimulation to assess VA inducibility, electrophysiological measurements (action potential duration), and molecular analysis (Kcnd3, Kv4.3 expression).
Main Results:
- CDC-treated rats exhibited reduced susceptibility to VA induction compared to placebo.
- CDC therapy led to a shortened action potential duration (APD) and increased APD homogeneity.
- Upregulation of transient outward potassium current density, Kcnd3 transcript, and Kv4.3 protein was observed in cardiomyocytes from CDC-treated rats; cardiac fibrosis was attenuated.
Conclusions:
- CDC therapy effectively decreases ventricular arrhythmias in HFpEF by modulating ion channel function, improving electrical stability, and reducing fibrosis.
- CDCs reverse electrical remodeling and suppress arrhythmogenesis in HFpEF, contrasting with other stem cells that may exacerbate arrhythmias.
- CDC treatment improves diastolic function, prolongs survival, and potentially reduces sudden death risk in HFpEF.
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