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Updated: Apr 5, 2026
Author Spotlight: Exploring the Relationship Between Lipotoxicity and HFpEF
Published on: February 23, 2024
From Heart Failure to Highly Unsaturated Fatty Acid Deficiency and Vice Versa: Bidirectional Heart and Liver
Peter Alter1, Tobias Glück1, Jens H Figiel2
1Department of Medicine, Pulmonary and Critical Care Medicine, University of Marburg, Marburg, Germany.
Insights
Highly unsaturated fatty acids (HUFA) like DHA are reduced in heart failure patients with increased left ventricular wall stress. This suggests HUFA levels are affected by cardiac dysfunction and may impact treatment efficacy.
Area of Science:
- Cardiology
- Biochemistry
- Nutritional Science
Background:
- Highly unsaturated fatty acids (HUFAs) show prognostic benefits in heart failure.
- Previous studies noted no benefit in preserved cardiac function, suggesting cardiac dysfunction severity is key.
- Hypothesis: Increased left ventricular (LV) wall stress alters hepatic HUFA metabolism, negatively impacting cardiac function.
Purpose of the Study:
- To investigate the relationship between left ventricular (LV) wall stress and serum levels of highly unsaturated fatty acids (HUFAs) in patients with suspected cardiomyopathy.
- To explore the potential role of cardiac dysfunction severity in HUFA metabolism.
Main Methods:
- Cardiac magnetic resonance imaging (CMR) was used to assess cardiac function in 30 patients.
- Serum fatty acid profiles were analyzed using gas chromatography/mass spectrometry.
- LV wall stress was calculated based on CMR-derived parameters.
Main Results:
- Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) levels were lower in patients with reduced LV ejection fraction or LV dilatation.
- Decreased DHA and EPA levels correlated with reduced LV ejection fraction.
- Reduced DHA levels were associated with increased LV end-diastolic and end-systolic wall stress.
Conclusions:
- Heart failure is associated with significantly reduced DHA levels, and to a lesser extent, EPA and arachidonic acid.
- Increased LV wall stress correlates with reduced DHA levels, potentially contributing to adverse cardiac consequences.
- Reduced pseudocholinesterase activity linked to increased LV wall stress suggests hepatic congestion (cardiohepatic syndrome), impacting HUFA metabolism and treatment effectiveness.
Background:
In several trials, beneficial prognostic effects of highly unsaturated fatty acids (HUFAs) in heart failure were shown. Because other studies showed no incremental benefit in nearly preserved cardiac function, the question arises, whether the degree of cardiac dysfunction is involved. It is hypothesized that increased left ventricular (LV) wall stress affects the endogenous hepatic HUFA metabolism, which in turn exhibits adverse cardiac consequences.
Methods:
Cardiac magnetic resonance imaging was performed in 30 patients with suspected cardiomyopathy. The serum fatty acid profile was assessed using gas chromatography/mass spectrometry.
Results:
Docosahexaenoic acid (DHA; P = 0.002) and eicosapentaenoic acid (EPA; by trend) levels were decreased in patients with reduced LV ejection fraction (≤ 50%) or LV dilatation (≥ 90 mL/m(2)). Decreased DHA (P = 0.003) and EPA (P = 0.022) levels were associated with a reduced LV ejection fraction. Decreased DHA level was correlated with increased end-diastolic (P = 0.047) and end-systolic LV wall stress (P = 0.001). Pseudocholinesterase activity was inversely correlated with end-diastolic (P = 0.020) and end-systolic LV wall stress (P = 0.025).
Conclusions:
DHA level was significantly reduced in heart failure. Similar, but less pronounced effects were found for EPA and arachidonic acid by trend. Increased LV wall stress was correlated with a reduced DHA level. Increased LV wall stress exhibits various adverse consequences (eg, increased oxygen consumption, favouring of arrhythmias, and an unfavourable remodelling). The increase of wall stress was paralleled by reduced HUFA level. Increased LV wall stress was correlated with reduced pseudocholinesterase, which is suggestive of hepatic congestion (ie, a cardiohepatic syndrome, involved in the altered fatty acid profile in heart failure) and has major consequences regarding the dose-efficacy of HUFA treatment.
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