Henrik Wiggers

Suppression of Circulating Free Fatty Acids with Acipimox in Chronic Heart Failure Patients Changes Whole Body Metabolism but Does not Affect Cardiac Function

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  • Department of Pharmacology
  • The Department of Cardiological Medicine B
  • Biomedical Radio Isotope Techniques
  • The Department of Endocrinology and Diabetes
  • Medical Research Laboratory
  • The Department of Internal Medicine and Cardiology A
Objectives: We studied cardiac and whole body effects of 28 days suppression of circulating FFA with acipimox in patients with chronic heart failure (HF). Background: Circulating free fatty acids (FFA) may worsen heart failure due to myocardial lipotoxicity and impaired energy generation. Methods: In a randomized double-blind cross-over design 24 HF patients with ischemic heart disease, LVEF 26+/- 2%, NYHA II and III (n=13 and 5) received 28 days acipimox treatment (250 mg4day(-1)) and placebo. Left ventricular ejection fraction, diastolic function, tissue-Doppler regional myocardial function, exercise capacity, non-invasive cardiac index, brain natriuretic peptide (Nt-pro-BNP), and whole body metabolic parameters were measured. Results: 18 patients were included for analysis. FFA was reduced 27% in the acipimox study arm (acipimox vs. placebo (day 28 - day 0) (mmol/L): -0.10+/-0.03 vs. +0.01+/-0.03; P<0.01). Glucose and insulin levels did not change. Acipimox tended to increase glucose and decrease lipid utilization rates at whole body level and changed significantly the effect of insulin on substrate utilization. Hyperinsulinemic euglycemic clamp M-value did not differ. Global and regional myocardial function did not differ. Exercise capacity, cardiac index, systemic vascular resistance, and Nt-pro-BNP were not affected by treatment. Conclusion: Acipimox caused minor changes in whole body metabolism and decreased FFA supply, but a long-term reduction in circulating FFA with acipimox did not change systolic or diastolic cardiac function or exercise capacity in patients with HF.
Original languageEnglish
JournalAmerican Journal of Physiology: Heart and Circulatory Physiology
Volume299
Issue4
Pages (from-to)H1220-5
Number of pages6
ISSN0363-6135
DOIs
Publication statusPublished - 2010

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