title: 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.
abstract: 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.
authors.affiliation: Fondazione S. Maugeri, IRCCS, Montescano, Pavia, Italy. mariateresa.larovere@fsm.it
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: La Rovere
authors.forename: Lidia
authors.initials: L
authors.lastname: Staszewsky
authors.forename: Simona
authors.initials: S
authors.lastname: Barlera
authors.forename: Roberto
authors.initials: R
authors.lastname: Maestri
authors.forename: Alessandro
authors.initials: A
authors.lastname: Mezzani
authors.forename: Paolo
authors.initials: P
authors.lastname: Midi
authors.forename: Roberto
authors.initials: R
authors.lastname: Marchioli
authors.forename: Aldo P
authors.initials: AP
authors.lastname: Maggioni
authors.forename: Gianni
authors.initials: G
authors.lastname: Tognoni
authors.forename: Luigi
authors.initials: L
authors.lastname: Tavazzi
authors.forename: Roberto
authors.initials: R
authors.lastname: Latini
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage; D000368:Aged; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D015716:Electrocardiography, Ambulatory / Q000379:methods; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage*; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D012016:Reference Values; D018570:Risk Assessment; D012720:Severity of Illness Index; D015996:Survival Rate; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000319:Adrenergic beta-Antagonists; D015525:Fatty Acids, Omega-3