Heart rate reduction by If-inhibition improves vascular stiffness and left ventricular systolic and diastolic function in a mouse model of heart failure with preserved ejection fraction
Key result
Selective heart rate reduction with ivabradine in a diabetic mouse model of HFPEF significantly lowered left ventricular end-systolic elastance (4.0 vs 6.0 mmHg/µL, P<0.01).
Why the study?
Does selective heart rate reduction by If-inhibition improve vascular stiffness and left ventricular function in a mouse model of HFPEF?
Population
Diabetic mice (db/db) as a model of heart failure with preserved ejection fraction (HFPEF), and control mice
Comparison
If-inhibitor ivabradine for 4 weeks vs Untreated db/db mice and control mice
Design
Preclinical
Follow-up
4 weeks
Authors
Discussion
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Member takes
Implication
Caution against clinical use in HFpEF; leaves open translation of ivabradine effects from diabetic mouse models.
Structured PICO
Does selective heart rate reduction by If-inhibition improve vascular stiffness and left ventricular function in a mouse model of HFPEF?
P
Population
Diabetic mice (db/db) as a model of heart failure with preserved ejection fraction (HFPEF), and control mice
I
Intervention
If-inhibitor ivabradine for 4 weeks
C
Comparator
Untreated db/db mice and control mice
O
Outcome
Aortic distensibility, left ventricular pressure-volume analysis (including end-systolic elastance and end-diastolic capacitance), and biochemical/histological characterizationsurrogate
Main Result
Absolute Event Rate: 4% vs 6%
p-value: p=<0.01
In a diabetic mouse model of HFpEF, heart rate reduction with ivabradine improved vascular stiffness, LV contractility, and diastolic function.
Limitations
- Requires confirmation in humans
Cite This Study
Reil et al. (2012) studied Heart failure with preserved ejection fraction (HFPEF) in diabetes mellitus. If-inhibitor ivabradine vs. Untreated diabetic mice (db/db) and healthy control mice was evaluated on Left ventricular end-systolic elastance (Ees) (p=<0.01). Selective heart rate reduction with ivabradine in a diabetic mouse model of HFPEF significantly lowered left ventricular end-systolic elastance (4.0 vs 6.0 mmHg/µL, P<0.01).