What is the clinical evidence from this study?

Population: Cardiometabolic heart failure with preserved ejection fraction (HFpEF) (n=36). Intervention: Dapagliflozin vs. Metabolic syndrome (MetS) control without dapagliflozin. Primary outcome: Ventricular arrhythmia (VA) episode frequency (p=<0.0001).

What does this research mean for the field?

Dapagliflozin reduces ventricular arrhythmogenesis in cardiometabolic HFpEF through epicardial fat remodeling, antifibrotic and anti-inflammatory effects, and electrophysiological stabilization. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

To evaluate the antiarrhythmic effects and electrophysiological mechanisms of dapagliflozin in a diet- and isoproterenol-induced rat model of cardiometabolic heart failure with preserved ejection fraction.

September 10, 2026Scientific ReportsOpen Access

Dapagliflozin reduces ventricular arrhythmogenesis and improves epicardial fat remodeling in a rat model of cardiometabolic HFpEF, associated with SIRT1–HIF1α-related biomarker changes

Q: What are the key findings of this study?

Dapagliflozin markedly reduced inducible ventricular arrhythmia episodes (median 0 vs 6, p<0.0001) and improved electrophysiological stability in a rat model of cardiometabolic HFpEF.

Q: What does this research mean for the field?

Dapagliflozin reduces ventricular arrhythmogenesis in cardiometabolic HFpEF through epicardial fat remodeling, antifibrotic and anti-inflammatory effects, and electrophysiological stabilization. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Q: What question did this study set out to answer?

To evaluate the antiarrhythmic effects and electrophysiological mechanisms of dapagliflozin in a diet- and isoproterenol-induced rat model of cardiometabolic heart failure with preserved ejection fraction.

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Key result

Dapagliflozin cuts inducible ventricular arrhythmia episodes to 0 in a cardiometabolic HFpEF rat model.

P<0.0001
n=36

Why the study?

Metabolic syndrome and obesity contribute to cardiometabolic HFpEF and ventricular arrhythmia, but the effects of SGLT2 inhibition on ventricular arrhythmia remain unclear.

Does dapagliflozin reduce ventricular arrhythmogenesis in a rat model of cardiometabolic HFpEF?

Key Points

To evaluate the antiarrhythmic effects and electrophysiological mechanisms of dapagliflozin in a diet- and isoproterenol-induced rat model of cardiometabolic heart failure with preserved ejection fraction.
Male Wistar rats were assigned to wild-type control, high-fat/high-glucose diet with isoproterenol-induced metabolic syndrome (MetS), or MetS treated with dapagliflozin (MetS-dapa).
Arrhythmia susceptibility was evaluated via in vivo programmed electrical stimulation (PES), and dynamic electrophysiological properties were measured using optical mapping.
Dapagliflozin significantly decreased inducible ventricular arrhythmia episodes (median 0 [range: 0–1] vs. 6 [3–7] in MetS, Dunn's test p < 0.0001) and total arrhythmia duration (7.21 s vs. 1230.42 s in MetS).
Optical mapping showed dapagliflozin reduced action potential duration at 70% repolarization (86.60 ± 5.61 ms vs. 120.60 ± 7.66 ms, p < 0.05) and flattened the maximum restitution slope (0.63 ± 0.02 vs. 1.20 ± 0.04, p < 0.05).
Treatment markedly decreased epicardial adipose tissue deposition (19.39 ± 1.29 vs. 47.20 ± 1.21, p < 0.05) and lowered systolic blood pressure (126.39 ± 3.18 mmHg vs. 152.21 ± 1.44 mmHg, p < 0.05).

Structured PICO

Does dapagliflozin reduce ventricular arrhythmogenesis in a rat model of cardiometabolic HFpEF?

Population

36 male Wistar rats with high-fat/high-glucose diet and isoproterenol-induced cardiometabolic HFpEF, treated for 4 weeks.

Intervention

Dapagliflozin treatment.

Comparator

High-fat/high-glucose diet-induced MetS without dapagliflozin, and wild-type (WT) controls.

Outcome

Ventricular arrhythmogenesis (VA inducibility, episode frequency, and duration induced by in vivo programmed electrical stimulation).surrogate

Main Result

Absolute Event Rate: 0% vs 6%

p-value: p=<0.0001

In a rat model of cardiometabolic HFpEF, dapagliflozin reduced ventricular arrhythmogenesis, improved epicardial fat remodeling, and stabilized electrophysiological properties.

Limitations

Only male rats were used, limiting generalizability to females.
Isoproterenol was used to accelerate HFpEF-like remodeling, which may cause direct myocardial injury independent of metabolic mechanisms.
Lack of an active comparator group (e.g., pair-fed weight-loss control or other glucose-lowering agent).
Inflammatory cytokines other than TNF-α and specific ventricular ionic currents were not directly measured.
SIRT1–HIF1α-related biomarker findings were based on association and do not establish a causal mechanism.
Causal relationships among FFA reduction, epicardial fat remodeling, inflammation, fibrosis, and VA suppression cannot be established from the present data alone.
NAD+ levels and SIRT1 activity were not directly measured or manipulated.
IL-1β, IL-6, IL-17, and specific ionic currents were not directly measured.

Discussion

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Implication

Supports antiarrhythmic investigation of dapagliflozin in cardiometabolic HFpEF; leaves open human translation from this animal model.

Cite This Study

Lin et al. (2026) studied Cardiometabolic heart failure with preserved ejection fraction (HFpEF) (n=36). Dapagliflozin vs. Metabolic syndrome (MetS) control without dapagliflozin was evaluated on Ventricular arrhythmia (VA) episode frequency (p=<0.0001). Dapagliflozin markedly reduced inducible ventricular arrhythmia episodes (median 0 vs 6, p<0.0001) and improved electrophysiological stability in a rat model of cardiometabolic HFpEF.

synapsesocial.com/papers/6aa27b4758559d80afc7467f https://doi.org/10.1038/s41598-026-68304-0

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Dapagliflozin reduces ventricular arrhythmogenesis and improves epicardial fat remodeling in a rat model of cardiometabolic HFpEF, associated with SIRT1–HIF1α-related biomarker changes

Key Points

Structured PICO

Main Result

Limitations

Discussion

Implication

Cite This Study

Dapagliflozin reduces ventricular arrhythmogenesis and improves epicardial fat remodeling in a rat model of cardiometabolic HFpEF, associated with SIRT1–HIF1α-related biomarker changes

Key Points

Structured PICO

Main Result

Limitations

Discussion

Implication

Cite This Study

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