Longitudinal Analysis of Quality of Life, Clinical, Radiographic, Echocardiographic, and Laboratory Variables in Dogs with Preclinical Myxomatous Mitral Valve Disease Receiving Pimobendan or Placebo: The EPIC Study

J Vet Intern Med. 2018 Jan;32(1):72-85. doi: 10.1111/jvim.14885. Epub 2017 Dec 6.


Background: Changes in clinical variables associated with the administration of pimobendan to dogs with preclinical myxomatous mitral valve disease (MMVD) and cardiomegaly have not been described.

Objectives: To investigate the effect of pimobendan on clinical variables and the relationship between a change in heart size and the time to congestive heart failure (CHF) or cardiac-related death (CRD) in dogs with MMVD and cardiomegaly. To determine whether pimobendan-treated dogs differ from dogs receiving placebo at onset of CHF.

Animals: Three hundred and fifty-four dogs with MMVD and cardiomegaly.

Materials and methods: Prospective, blinded study with dogs randomized (ratio 1:1) to pimobendan (0.4-0.6 mg/kg/d) or placebo. Clinical, laboratory, and heart-size variables in both groups were measured and compared at different time points (day 35 and onset of CHF) and over the study duration. Relationships between short-term changes in echocardiographic variables and time to CHF or CRD were explored.

Results: At day 35, heart size had reduced in the pimobendan group: median change in (Δ) LVIDDN -0.06 (IQR: -0.15 to +0.02), P < 0.0001, and LA:Ao -0.08 (IQR: -0.23 to +0.03), P < 0.0001. Reduction in heart size was associated with increased time to CHF or CRD. Hazard ratio for a 0.1 increase in ΔLVIDDN was 1.26, P = 0.0003. Hazard ratio for a 0.1 increase in ΔLA:Ao was 1.14, P = 0.0002. At onset of CHF, groups were similar.

Conclusions and clinical importance: Pimobendan treatment reduces heart size. Reduced heart size is associated with improved outcome. At the onset of CHF, dogs treated with pimobendan were indistinguishable from those receiving placebo.

Keywords: Cardiology; Cardiovascular; Echocardiography; Endocardiosis; Heart Failure; Mitral regurgitation.

Publication types

  • Clinical Trial

MeSH terms

  • Animals
  • Cardiomegaly / drug therapy
  • Cardiomegaly / veterinary
  • Cardiotonic Agents / therapeutic use*
  • Dog Diseases / drug therapy
  • Dogs
  • Echocardiography / veterinary
  • Heart Diseases / mortality
  • Heart Diseases / veterinary
  • Heart Failure / etiology
  • Heart Failure / veterinary
  • Mitral Valve Prolapse / diagnostic imaging
  • Mitral Valve Prolapse / drug therapy*
  • Mitral Valve Prolapse / pathology
  • Prospective Studies
  • Pyridazines / therapeutic use*
  • Quality of Life


  • Cardiotonic Agents
  • Pyridazines
  • pimobendan