Control of cardiac chronotropic function in patients after heart transplantation: effects of ivabradine and metoprolol succinate on resting heart rate in the denervated heart

Clin Res Cardiol. 2018 Feb;107(2):138-147. doi: 10.1007/s00392-017-1165-3. Epub 2017 Nov 2.

Abstract

Background: Patients after heart transplantation (HTX) present with sinus tachycardia due to graft denervation. As elevated heart rates negatively affect survival, the aim of this study was to analyze the effects of ivabradine vs metoprolol succinate on heart rate, left ventricular (LV) mass and survival following HTX.

Methods: This observational retrospective single-center study assessed 84 patients continuously receiving either ivabradine (n = 40) or metoprolol succinate (n = 44) within 2 years after HTX. Patients with dual therapy (ivabradine and metoprolol succinate), other beta blockers, amiodarone, or digitalis were excluded. Patient characteristics, post-transplant medication, heart rates, LV mass, and survival were investigated.

Results: Analysis of patient characteristics, immunosuppressive drug regimen, and post-transplant medication showed no significant differences between groups except for ivabradine and metoprolol succinate. Baseline heart rates differed not significantly between patients treated with ivabradine [87.0 beats per minute (bpm)] and metoprolol succinate (86.2 bpm; P = 0.6395). At 2-year follow-up, patients with ivabradine (76.7 bpm) had a significantly lower heart rate compared to baseline (P < 0.0001) and to metoprolol succinate (82.0 bpm; P = 0.0283). LV mass in patients receiving ivabradine was lower at 2-year follow-up compared to baseline (P = 0.0067) and patients receiving metoprolol succinate (P = 0.0179). Patients with ivabradine had a superior 2-year survival after HTX (P = 0.0049).

Conclusion: Treatment with ivabradine in patients within 2 years after HTX significantly reduced post-transplant heart rate and LV mass and was associated with a superior survival in comparison with patients receiving metoprolol succinate.

Keywords: Heart rate; Heart transplantation; Ivabradine; Metoprolol succinate; Mortality.

Publication types

  • Comparative Study
  • Observational Study

MeSH terms

  • Adult
  • Anti-Arrhythmia Agents / adverse effects
  • Anti-Arrhythmia Agents / therapeutic use*
  • Benzazepines / adverse effects
  • Benzazepines / therapeutic use*
  • Female
  • Germany
  • Heart / drug effects*
  • Heart / innervation
  • Heart Rate / drug effects*
  • Heart Transplantation / adverse effects*
  • Heart Transplantation / mortality
  • Humans
  • Hypertrophy, Left Ventricular / drug therapy
  • Hypertrophy, Left Ventricular / etiology
  • Hypertrophy, Left Ventricular / physiopathology
  • Ivabradine
  • Kaplan-Meier Estimate
  • Male
  • Metoprolol / adverse effects
  • Metoprolol / therapeutic use*
  • Middle Aged
  • Retrospective Studies
  • Risk Factors
  • Tachycardia, Sinus / drug therapy*
  • Tachycardia, Sinus / etiology
  • Tachycardia, Sinus / mortality
  • Tachycardia, Sinus / physiopathology
  • Time Factors
  • Treatment Outcome
  • Ventricular Function, Left / drug effects
  • Ventricular Remodeling / drug effects

Substances

  • Anti-Arrhythmia Agents
  • Benzazepines
  • Ivabradine
  • Metoprolol