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

Boswood, A and Gordon, S G and Häggström, J and Wess, G and Stepien, R L and Oyama, M A and Keene, B W and Bonagura, J D and MacDonald, K A and Patteson, M and Smith, S and Fox, P R and Sanderson, K and Woolley, R and Szatmári, V and Menaut, P and Church, W M and O'Sullivan, M L and Jaudon, J P and Kresken, J-G and Rush, J and Barrett, K A and Rosenthal, S L and Saunders, A B and Ljungvall, I and Deinert, M and Bomassi, E and Estrada, A H and Fernández-Del Palacio, M J and Moise, N S and Abbott, J A and Fujii, Y and Spier, A and Luethy, M W and Santilli, R A and Uechi, M and Tidholm, A and Schummer, C and Watson, P (2018) 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. JOURNAL OF VETERINARY INTERNAL MEDICINE, 32 (1). pp. 72-85. ISSN 1939-1676

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Abstract

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 (Delta) 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 Delta LVIDDN was 1.26, P = 0.0003. Hazard ratio for a 0.1 increase in Delta LA: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.

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