(16-09-11) High-Dose n-3 LC-PUFAs Associated with Increased Left Ventricular Ejection Fraction in Advanced Heart Failure

Individuals with chronic heart failure (CHF) may face various consequences of their disease in other tissues. These include impaired kidney function, fluid accumulation, endothelial dysfunction, chronic inflammation and other disorders resulting from insufficient blood flow to the organs. Surgical interventions and medications are widely used to improve the prognosis of patients with CHF, while lifestyle changes such as a low-fat, low-sodium diet may be recommended. An additional dietary strategy may be the inclusion of long-chain omega-3 polyunsaturated fatty acids (n-3 LC-PUFAs). Evidence from the Gruppo Italiano per lo Studio della Sopravvivenza nell?Infarto Miocardico (GISSI) study in Italy suggested a small but significant benefit of mortality in CHF patients who consumed approximately 1 g/day of n-3 LC-PUFAs for almost 4 years. In addition, CHF patients who consumed n-3 LC-PUFAs for 2 or 3 years had significantly increased left ventricular ejection fraction (11%) at the end of 2 and 3 years.Several research groups have recently published findings from randomized trials with n-3 LC-PUFA supplementation in CHF patients. In this study, investigators at the Medical University of Vienna, Austria, explored the effects of 2 doses of n-3 LC-PUFAs compared with placebo in patients with severe CHF of nonischemic origin who were stable with optimum CHF treatment for at least 3 months. On average, participants had left ventricular ejection fractions of 25% or less. From 57 eligible patients, 49 were randomized to the treatment groups and 43 completed the study.The participants were randomized to receive approximately 1 or 4 g/day of n-3 LC-PUFAs or placebo for 12 weeks. The n-3 LC-PUFA capsules each contained at least 465 mg of eicosapentaenoic acid (EPA) and 375 mg of docosahexaenoic acid (DHA) as ethyl esters and the placebo capsules contained gelatin.The physiological parameters measured at baseline and after 3 months included flow-mediated vasodilation as a marker of endothelial function, left ventricular ejection fraction assessed using radionuclide ventriculography, inflammatory markers (IL-6 and TNF-?) and peak exercise oxygen consumption assessed using symptom-limited maximal incremental cycle exercise testing with gas exchange measurements (Figure 1).After 3 months? treatment, left ventricular ejection fraction increased significantly from baseline in both n-3 LC-PUFA treatment groups, with no change in the placebo group. Treatment and dose effects were statistically significant (Figure 2). Flow-mediated dilation increased significantly only in patients consuming 4 g/day of n-3 LC-PUFAs, increasing from 8.4% at baseline to 11.6% after 3 months of treatment. Interleukin-6 decreased significantly in the high n-3 LC-PUFA group only, but the reduction in TNF-? in this group did not reach statistical significance. The investigators noted that these patients had low concentrations of these inflammatory markers at baseline, which suggests that further reduction might be difficult to achieve.Of those who completed the study, 26 performed the exercise test. Peak oxygen volume increased significantly only in the highest n-3 LC-PUFA group, but was unchanged in the placebo patients. Changes in exercise capacity were not significant. It has been reported previously that exercise capacity in CHF does not correlate with left ventricular ejection fraction, but is related to peripheral blood and nutrient flow.The key finding in this report is the dose-dependent effect of n-3 LC-PUFAs on increasing left ventricular ejection fraction in patients with advanced CHF. The study suggests that high doses-about 4 g/day-of n-3 LC-PUFAs also decrease inflammatory cytokine production, improve endothelial function and modestly increase exercise capacity. Larger trials are required to confirm these observations.
Moertl D, Hammer A, Steiner S, Hutuleac R, Vonbank K, Berger R. Dose-dependent effects of omega-3-polyunsaturated fatty acids on systolic left ventricular function, endothelial function, and markers of inflammation in chronic heart failure of nonischemic origin A double-blind, placebo-controlled, 3-arm study.

SOURCE: Am Heart J 2011;161:915.e1-9 [Pubmed]

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