Elevation of Plasma Milrinone Concentrations in Stage D Heart Failure Associated With Renal Dysfunction

Purpose: To determine steady state milrinone concentrations in patients with stage D heart failure (HF) with and without renal dysfunction Methods: We retrospectively identified patients with stage D HF at a single medical center on continuous milrinone infusion at the time of plasma collection for entry into a research registry database. Milrinone was prescribed and titrated to improve hemodynamic and clinical status by a cardiologist. Plasma samples were obtained at steady state milrinone concentrations. Patients were stratified by creatinine clearance (CrCl) into 4 groups: group 1 (CrCl >60 mL/min), group 2 (CrCl 60-30 mL/min), group 3 (CrCl <30 mL/min), and group 4 (intermittent hemodialysis). Retrospective chart review was performed to quantify the postmilrinone hemodynamic changes by cardiac catheterization and electrophysiologic changes by implantable cardiac defibrillator (ICD) interrogation. Results: A total of 29 patients were identified: group 1 (n = 14), group 2 (n = 10), group 3 (n = 3), and group 4 (n = 2). The mean infusion rate (0.391 +/- 0.08 mu g/kg/min) did not differ between groups (P = 0.14). The mean milrinone concentration was 451 +/- 243 ng/mL in group 1, 591 +/- 293 ng/mL in group 2, 1575 +/- 962 ng/mL in group 3, and 6252 +/- 4409 ng/mL in group 4 (P<0.05 compared to groups 1). There was no difference in postmilrinone hemodynamic improvements between the groups (P=0.41). The ICD interrogation revealed limited comparisons, but 6 of the 8 postmilrinone ventricular tachycardia episodes requiring defibrillation occurred in group 4 patients. Conclusion: Patients with stage D HF having severe renal dysfunction have elevated milrinone concentrations. Future studies of milrinone concentrations are warranted to investigate the potential risk of life-threatening arrhythmias and potential dosing regimens in renal dysfunction.