What is the clinical evidence from this study?

Study design: Other. Population: Heart failure with reduced ejection fraction (HFrEF) (n=19). Intervention: High-fat diet (HFD) vs. Regular chow diet (3.1% of calories from fat). Primary outcome: Final left ventricular ejection fraction (LVEF) (p=0.012).

What does this research mean for the field?

A two-month high-fat diet significantly improves median left ventricular ejection fraction to 54% compared to 41% with a control diet and restores cardiac metabolism in a pig model of heart failure with reduced ejection fraction. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

This research investigates the effects of a high-fat diet on cardiac metabolism and function in a pig model of heart failure with reduced ejection fraction.

March 29, 2026Basic Research in Cardiology0 citationsOpen Access

A high-fat diet nutritional intervention reprograms cardiac metabolism and improves systolic function in a pig model of heart failure with reduced ejection fraction

CGCarlos Galán-Arriola DPDaniel Pérez-Camargo AFAlessia Ferrarini

Key Result

A two-month high-fat diet significantly improved median left ventricular ejection fraction to 54% compared to 41% with a control diet in a pig model of heart failure with reduced ejection fraction.

Key Points

This research investigates the effects of a high-fat diet on cardiac metabolism and function in a pig model of heart failure with reduced ejection fraction.
Pigs were induced with heart failure via coronary artery stenosis.
Pigs were randomized to receive either a high-fat diet or a control diet for two months.
Cardiac function was assessed using contrast-enhanced cardiac magnetic resonance and 18 FDG-PET/CT.
Post-treatment hearts were analyzed for metabolic and structural changes.
LVEF improved from 38% to 54% in high-fat diet pigs (p = 0.036).
Diets with high fat resulted in significantly reduced fibrosis (0.45% vs 6.23%, p = 0.0047).
Metabolic reversion occurred in dysfunctional myocardium of high-fat diet pigs (0.46 vs 1.80 counts, p = 0.016).
Histological analysis showed less mitochondrial fragmentation and reduced lipid droplet density in high-fat diet pigs.

Structured PICO

Does a high-fat diet improve LVEF in a pig model of HFrEF?

Population

2-month-old castrated male Large White pigs with induced heart failure with reduced ejection fraction (HFrEF) and metabolic switch secondary to progressive coronary artery stenosis

Intervention

High-fat diet (HFD, chow diet supplemented with 20% lard, 22.4% calories from fat)

Comparator

Control diet (regular chow diet, 3.1% calories from fat)

Outcome

Between-group difference in final LVEFsurrogate

In a pig model of HFrEF, a high-fat diet nutritional intervention successfully reprogrammed cardiac metabolism toward fatty acid utilization and significantly improved systolic function.

Main Result

Absolute Event Rate: 54% vs 41%

p-value: p=0.012

Limitations

High drop-out rate due to sudden cardiac death during the trial phase (6 of 19 animals died)
Small final sample size of animals completing the study (n=13)
Findings from an animal model may not fully translate to human clinical heart failure

Abstract

Abstract Most forms of heart failure are characterized by a metabolic switch from the use of fatty acids to glucose as the main fuel source for ATP generation in the myocardium. Whether metabolic reprogramming is a therapeutic target remains controversial. In this study, heart failure with reduced ejection fraction (HFrEF) and metabolic switch (i.e., increased myocardial glucose uptake) was induced in pigs by generating viable dysfunctional myocardium secondary to progressive coronary artery stenosis. Pigs ( n = 19) were then randomized to a high-fat diet (HFD, chow diet supplemented with 20% lard) or control diet (no supplementation) for two months. Pre- and post-nutritional treatment contrast-enhanced cardiac magnetic resonance (CMR) and 18 FDG-PET/CT studies were performed. Hearts were then harvested for further analysis. LVEF significantly improved in pigs receiving the 2-month HFD (38% 33, 43 to 54% 47, 62, p = 0.036) but remained unchanged in control-diet pigs (36% 35, 45 to 41% 38, 43, p = 0.24). HFD-fed pigs had a smaller extent of fibrosis after the dietary intervention (late gadolinium enhancement 0.45% LV 0.17, 1.67 vs 6.23 5.54, 9.57, p = 0.0047). On 18 FDG-PET, a reversion of the metabolic reprogramming in the LAD-dysfunctional myocardium was observed only in HFD-fed pigs (0.46 counts 0.21, 0.65 vs 1.80 1.53, 2.83, p = 0.016). Transmission electron microscopy of explanted hearts revealed less fragmented mitochondrial and a lower lipid droplet density in cardiomyocytes from HFD-fed pigs (38 per 10 µm3 34, 50 vs 96 78, 124, p = 0.022), and this was accompanied by increased expression of genes involved in fatty acid metabolism and downregulation of genes encoding glucose import proteins. In conclusion, in a large animal model of HFrEF secondary to myocardial dysfunction with a metabolic switch, a nutritional intervention based on HFD feeding was associated with a cardiac metabolic restoration of fatty acid substrate use, restoration of cardiomyocyte lipid trafficking and significantly improved systolic function.

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