High Fat Diet for Cardiac Metabolic Reprogramming

Summary

Heart failure (HF) continues to be a leading cause of morbidity and mortality worldwide, despite advances in treatment. HF is often characterized by an altered metabolism in the heart, where glucose is favored over fatty acids as the primary energy substrate. This metabolic shift has been hypothesized to contribute to disease progression. Previous studies using animal models have demonstrated that restoring fatty acid metabolism through dietary intervention can reverse the adverse metabolic effects and improve heart function. A transgenic murine model with mitochondrial defects, for instance, exhibited improved cardiac function after an HFD intervention. These findings were reinforced by a translational pig model of non-ischemic DCM, where a high-fat diet significantly improved LVEF compared to a standard diet. Building upon these promising preclinical results, a small-scale human study showed that lipid infusion, rather than glucose, improved cardiac function in HF patients. However, the long-term benefits of a HFD in heart failure patients have yet to be thoroughly explored. The HF4HF trial aims to fill this gap by evaluating the effects of an HFD over a two-month period in patients with non-ischemic DCM and reduced LVEF. The "High Fat Diet for Heart Failure" (HF4HF) study is a proof-of-concept randomized controlled trial designed to investigate the efficacy of a high-fat diet (HFD) as a therapeutic intervention in patients with non-ischemic dilated cardiomyopathy (DCM) and reduced left ventricular ejection fraction (LVEF). The study hypothesizes that cardiac metabolic reprogramming, achieved through a controlled nutritional intervention involving an HFD, can enhance systolic function, myocardial energetics, and overall heart function in heart failure (HF) patients. Cofunded by the European Commission and national entities, the trial is spearheaded by a consortium of cardiovascular research centers across four countries: Spain, Italy, France, and Romania.

Eligibility

Inclusion Criteria:

* Patients of both sexes and ≥18 years old
* Patients diagnosed with HF secondary to non-ischemic DCM, according to ESC guidelines definition,1 with or without a known genetic basis.
* LVEF ≤49% according to the baseline CMR.
* Optimized HF guideline-directed medical therapy for at least 3 months prior to inclusion.
* Patients who have provided informed consent.

Exclusion Criteria:

* Prior diagnosis of ischemic DCM.
* Prior diagnosis of established atherosclerotic cardiovascular disease (angina/myocardial infarction, transient ischemic attack/stroke, lower limb ischemia or at any other peripheral level).
* Changes in HF therapies within the last 3 months.
* HF decompensation within the previous 3 months, including HF hospitalization or the need of ambulatory intravenous diuretic or inotropic treatment such as levosimendan.
* Uncontrolled dyslipidemia, defined as LDL-cholesterol \>160 mg/dL and/or triglycerides \>200 mg/dL, despite treatment.
* Any contraindication for CMR:

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* Liver and biliary diseases, including prior diagnosis of non-alcoholic fatty liver disease and unoperated cholelithiasis.
* Prior episodes of acute pancreatitis or chronic pancreatitis.
* Prior fish or nut allergy.
* Life expectancy less than 12 months.
* Pregnancy or planned pregnancy for the next 4 months.
* Current lactation.
* Patients participating in other randomized clinical trial.
* Impossibility to consent or undergo study follow-up

Conditions3

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