The Effect of Omega-3 Polyunsaturated Fatty Acids in Congestive Heart Failure

A diet rich in Omega-3 polyunsaturated fatty acids Omega 3 reduces plasma triglycerides and
the risk for ischemic heart disease1, and may exert direct antiarrhythmic effect on the
myocardium 2-9. A post-hoc analysis of the GISSI-Prevenzione trial demonstrated a reduction
in all-cause and sudden mortality in a subgroup of nearly 2000 post-infarction patients
with left ventricular dysfunction 10. This provocative finding has now been prospectively
studied in a large-scale, randomized, double-blind study designed to investigate the effects
of Omega 3 on mortality and morbidity in patients with symptomatic heart failure (the GISSI
Heart Failure project). The results of the GISSI-HF trial demonstrate that 1 g per day of
Omega 3 is associated with 9% reduction in mortality and cardiovascular admissions in
patients with predominantly systolic heart failure, when added to optimal medical therapy11.

The mechanism(s) underlying these beneficial effects remains to be elucidated and will be
critical in fully exhausting the therapeutic benefits of Omega 3 in CHF. We have recently
demonstrated that lipid oxidation during acute exercise is altered in patients with CHF 12
and that the degree of this alteration carries prognostic significance. It is conceivable
that Omega 3 modulates lipid oxidation during exercise and thereby favorably effect outcome.
Accordingly we propose to study the effect of Omega 3 on lipid oxidation during exercise in
CHF. We will further examine VO2 and endothelial function at present the principal surrogate
markers for survival in CHF 13.

Inclusion Criteria:

All subjects with CHF due to systolic dysfunction followed at the outpatient facilities of
Columbia University Medical Center will be screened and subjects will be asked to
participate if the following criteria are met:

- Older than 18 years.

- Symptomatic heart failure (New York Heart Association functional class II-III).

- Ischemic or non-ischemic cardiomyopathy.

- Left ventricular ejection fraction (EF) 40% or lower.

- Peak oxygen uptake (VO2, peak) between 10 and 17 mL O2/min/kg.

- Be on appropriate, stable medical treatments for heart failure, including (unless
shown to be intolerant) a diuretic, an angiotensin-converting enzyme inhibitor and/or
angiotensin-receptor blocker and a beta-blocker, pacemaker or ICD or CRT.

Exclusion Criteria:

- Unable to perform treadmill exercise

- Pregnancy

- Recent myocardial infarction (within 3 months).

- Clinically significant angina.

- Hospitalization for heart failure requiring intravenous treatments within 30 days.

- Allergy to fish