acipimox and Chronic-Disease

Circulating free fatty acids (FFAs) may worsen heart failure (HF) due to myocardial lipotoxicity and impaired energy generation. We studied cardiac and whole body effects of 28 days of suppression of circulating FFAs with acipimox in patients with chronic HF. In a randomized double-blind crossover design, 24 HF patients with ischemic heart disease [left ventricular ejection fraction: 26 ± 2%; New York Heart Association classes II (n = 13) and III (n = 5)] received 28 days of acipimox treatment (250 mg, 4 times/day) and placebo. Left ventricular ejection fraction, diastolic function, tissue-Doppler regional myocardial function, exercise capacity, noninvasive cardiac index, NH(2)-terminal pro-brain natriuretic peptide (NT-pro-BNP), and whole body metabolic parameters were measured. Eighteen patients were included for analysis. FFAs were reduced by 27% in the acipimox-treated group [acipimox vs. placebo (day 28-day 0): -0.10 ± 0.03 vs. +0.01 ± 0.03 mmol/l, P < 0.01]. Glucose and insulin levels did not change. Acipimox tended to increase glucose and decrease lipid utilization rates at the whole body level and significantly changed the effect of insulin on substrate utilization. The 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. In conclusion, acipimox caused minor changes in whole body metabolism and decreased the FFA supply, but a long-term reduction in circulating FFAs with acipimox did not change systolic or diastolic cardiac function or exercise capacity in patients with HF.

Topics: Adult; Aged; Aged, 80 and over; Blood Glucose; Chronic Disease; Cross-Over Studies; Double-Blind Method; Exercise Tolerance; Fatty Acids, Nonesterified; Female; Heart; Heart Failure; Humans; Hypolipidemic Agents; Male; Metabolism; Middle Aged; Pyrazines; Stroke Volume; Vascular Resistance

Currently, with the rapidly increasing number of patients with heart failure due to chronic coronary artery disease, the need for viability studies to guide treatment in these patients is increasing. The most accurate method for viability assessment is metabolic imaging with (18)F-FDG with PET or SPECT. To obtain excellent image quality in all patients, the (18)F-FDG studies should be performed during hyperinsulinemic euglycemic clamping. However, this approach is time-consuming and is not feasible in busy nuclear medicine laboratories. Recently, the use of a nicotinic acid derivative, acipimox, has been suggested, but limited data are available on the image quality of the (18)F-FDG studies using this approach.. We evaluated the feasibility and image quality of (18)F-FDG SPECT (with dual-isotope simultaneous acquisition (DISA) using (99m)Tc-tetrofosmin to assess perfusion) after acipimox administration in 50 nondiabetic patients. The image quality of both (18)F-FDG and (99m)Tc-tetrofosmin was assessed visually and quantitatively using myocardium-to-blood-pool (M/B) ratios as a measure of target-to-background ratio. The image quality and diagnostic value of DISA (99m)Tc-tetrofosmin SPECT was compared with standard (99m)Tc-tetrofosmin SPECT at baseline.. After acipimox administration, the plasma levels of free fatty acids were extremely low (68 +/- 89 nmol/L). No severe side effects were observed, only paroxysmal flushing. The (18)F-FDG image quality was good in 46 patients (92%) and moderate but still interpretable in the other 4 patients (8%). The clinical information of the baseline (99m)Tc-tetrofosmin SPECT was retained in the DISA (99m)Tc-tetrofosmin SPECT images because we did observe no substantial fill-in of perfusion defects by high (18)F-FDG uptake in the same segment.. Cardiac (18)F-FDG SPECT after acipimox is safe and resulted consistently in good image quality; this simple approach may be the method of choice for routine cardiac metabolic imaging.

Topics: Administration, Oral; Chronic Disease; Coronary Artery Disease; Echocardiography; Feasibility Studies; Female; Fluorodeoxyglucose F18; Heart; Humans; Male; Middle Aged; Organophosphorus Compounds; Organotechnetium Compounds; Pyrazines; Radiopharmaceuticals; Tomography, Emission-Computed, Single-Photon; Ventricular Dysfunction, Left