n-3PUFA and Holter-derived autonomic variables in patients with heart failure: data from the Gruppo Italiano per lo Studio della Sopravvivenza nell'Insufficienza Cardiaca (GISSI-HF) Holter substudy.

BACKGROUND: n-3 Polyunsaturated fatty acid (n-3PUFA) supplementation in the Gruppo Italiano per lo Studio della Sopravvivenza nell'Insufficienza Cardiaca (GISSI-HF) study reduced total mortality in patients with heart failure (HF), but the mechanism of action is still debated. The hypothesis of the present GISSI-HF substudy was that n-3PUFA may have beneficial effects on cardiac autonomic control.

OBJECTIVE: To evaluate the effect of 1 g/day of n-3PUFA vs placebo on heart rate variability variables, deceleration capacity, and turbulence slope.

METHODS: The GISSI-HF study enrolled patients with HF of any cause and severity. Twenty-four-hour (range 16-24 hours) Holter recordings were performed and analyzed in 388 patients at baseline, 3 months, and 12 months. Baseline characteristics were compared by using the χ(2) test, t test, or nonparametric Wilcoxon 2-sample test. Changes over time were tested by using the analysis of covariance adjusted by baseline values.

RESULTS: At baseline, 36% of the patients were older than 70 years, 82% were men, 92% presented a left ventricular ejection fraction<40%, and 80% were in New York Heart Association class II. An increase in mean RR interval, standard deviation of all normal-to-normal RR intervals, very low frequency power (all P<.05), and turbulence slope (P = .05) was observed after 3 months in the n-3PUFA group compared to the placebo group, independently of the frequency of dietary fish consumption or beta-blocker treatment. These differences between study groups were no longer statistically significant at 12 months. A per-protocol analysis in patients compliant with study treatment showed similar results.

CONCLUSIONS: n-3PUFA supplementation partially restored autonomic modulation in patients with chronic HF; this effect was maximal after 3 months of treatment.