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Heart rate-induced modifications of concentric left ventricular hypertrophy: exploration of a novel therapeutic
Franziska J Klein1, Stephen Bell1, K Elisabeth Runte1
1Cardiology Division, University of Vermont College of Medicine, Burlington, Vermont.
Insights
Increasing heart rate may benefit heart failure with preserved ejection fraction (HFpEF) by reducing left ventricular wall thickness and improving heart function. This novel approach could offer a new therapeutic strategy for HFpEF.
Area of Science:
- Cardiology
- Translational Medicine
- Cardiac Physiology
Background:
- Lowering heart rate benefits heart failure with reduced ejection fraction (HFrEF) by reducing left ventricular (LV) size.
- Heart failure with preserved ejection fraction (HFpEF) is common and lacks effective treatments.
- HFpEF is associated with LV concentric remodeling and hypertrophy, with unknown effects of heart rate.
Purpose of the Study:
- To investigate the effects of increased heart rate on a concentrically hypertrophied LV.
- To explore if heart rate modulation can induce beneficial remodeling in HFpEF-like conditions.
Main Methods:
- Utilized a porcine model with established concentric LV hypertrophy and fibrosis.
- Assessed the impact of a moderate increase in heart rate on LV structure and function.
Main Results:
- A moderate heart rate increase reduced LV wall thickness and normalized LV chamber volumes.
- Myocardial fibrosis decreased, and LV compliance improved with increased heart rate.
- These effects were titratable, reversible, and did not induce heart failure.
Conclusions:
- Increased heart rate may promote beneficial LV remodeling in HFpEF.
- Findings suggest a potential novel therapeutic strategy targeting heart rate for HFpEF.
- This approach could address the underlying structural substrate of HFpEF.
Abstract:
Lowering the heart rate is considered to be beneficial in heart failure (HF) with reduced ejection fraction (HFrEF). In a dilated left ventricle (LV), pharmacological heart rate lowering is associated with a reduction in LV chamber size. In patients with HFrEF, this structural change is associated with better survival. HF with preserved ejection fraction (HFpEF) is increasingly prevalent but, so far, without any evidence-based treatment. HFpEF is typically associated with LV concentric remodeling and hypertrophy. The effects of heart rate on this structural phenotype are not known. Analogous with the benefits of a low heart rate on a dilated heart, we hypothesized that increased heart rates could lead to potentially beneficial remodeling of a concentrically hypertrophied LV. This was explored in an established porcine model of concentric LV hypertrophy and fibrosis. Our results suggest that a moderate increase in heart rate can be used to reduce wall thickness, normalize LV chamber volumes, decrease myocardial fibrosis, and improve LV compliance. Our results also indicate that the effects of heart rate can be titrated, are reversible, and do not induce HF. These findings may provide the rationale for a novel therapeutic approach for HFpEF and its antecedent disease substrate.
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