From Heart Failure to Highly Unsaturated Fatty Acid Deficiency and Vice Versa: Bidirectional Heart and Liver Interactions

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 (similar to 50%) or LV dilatation (similar to 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.