Low-dose β-blocker in combination with milrinone safely improves cardiac function and eliminates pulsus alternans in patients with acute decompensated heart failure

Circ J. 2012;76(7):1646-53. doi: 10.1253/circj.cj-12-0033. Epub 2012 Apr 5.


Background: The purpose of this study was to determine whether a low-dose β-blocker, in combination with milrinone, improves cardiac function in acute decompensated heart failure (ADHF) with tachycardia.

Methods and results: Twenty ADHF patients (New York Heart Association classification III, n=1, and IV, n=19; heart rate [HR], 107±12 beats/min; left ventricular ejection fraction, 24±7%; cardiac index [CI], 2.2±0.6 L·min(-1)·m(-2); pulmonary capillary wedge pressure [PCWP], 26±8 mmHg) were enrolled in this study. The patients first underwent conventional therapy with milrinone, vasodilators and diuretics; landiolol (1.5-6.0 µg·kg(-1)·min(-1); i.v.), which is an ultra-short-acting β(1)-selective blocker, was then added to the treatment regimen to study its effect on hemodynamics. Low-dose landiolol (1.5 µg·kg(-1)·min(-1)) significantly reduced HR by 11% without changing blood pressure (BP) and CI, whereas higher doses (≥3.0 µg·kg(-1)·min(-1)) tended to decrease BP and CI while increasing PCWP and systemic vascular resistance. After treatment with landiolol (1.5 µg·kg(-1)·min(-1)), hemodynamic parameters such as PCWP, stroke volume index, SvO(2), rate pressure product, filling time/RR, E/e', and Tei index were significantly improved.

Conclusions: A low-dose β-blocker in combination with milrinone improved cardiac function in ADHF patients with tachycardia; therefore, it may be considered as an adjunct therapy for use when standard therapy with milrinone is not effective at slowing HR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adrenergic beta-Antagonists / administration & dosage*
  • Adult
  • Aged
  • Arrhythmias, Cardiac / drug therapy*
  • Arrhythmias, Cardiac / etiology
  • Arrhythmias, Cardiac / physiopathology
  • Cardiotonic Agents / administration & dosage*
  • Chi-Square Distribution
  • Drug Therapy, Combination
  • Female
  • Heart Failure / complications
  • Heart Failure / drug therapy*
  • Heart Failure / physiopathology
  • Heart Rate / drug effects
  • Hemodynamics / drug effects*
  • Humans
  • Japan
  • Male
  • Middle Aged
  • Milrinone / administration & dosage*
  • Morpholines / administration & dosage*
  • Prospective Studies
  • Pulmonary Wedge Pressure / drug effects
  • Recovery of Function
  • Stroke Volume
  • Time Factors
  • Treatment Outcome
  • Urea / administration & dosage
  • Urea / analogs & derivatives*
  • Ventricular Dysfunction, Left / drug therapy*
  • Ventricular Dysfunction, Left / etiology
  • Ventricular Dysfunction, Left / physiopathology
  • Ventricular Function, Left / drug effects*


  • Adrenergic beta-Antagonists
  • Cardiotonic Agents
  • Morpholines
  • landiolol
  • Urea
  • Milrinone