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

A Boswood; Shauna Gordon-McKeon; J Häggström; G Wess; R L Stepien; M A Oyama; B W Keene; J Bonagura; K A MacDonald; M Patteson; S Smith; P R Fox; K Sanderson; S.R. Woolley; V Szatmári; P Menaut; W M Church; M L O'Sullivan; J-P Jaudon; J-G Kresken; John Rush; A.K. Barrett; S L Rosenthal; B.A.C. Saunders; I Ljungvall; M Deinert; E Bomassi; A H Estrada; M J Fernandez Del Palacio; N S Moise; J A Abbott; Y Fujii; A Spier; M W Luethy; R A Santilli; M Uechi; A Tidholm; C Schummer; Poppy Watson

doi:10.1111/jvim.14885

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

A Boswood, Shauna Gordon-McKeon, J Häggström, G Wess, R L Stepien, M A Oyama, B W Keene, J Bonagura, K A MacDonald, M Patteson, S Smith, P R Fox, K Sanderson, S.R. Woolley, V Szatmári, P Menaut, W M Church, M L O'Sullivan, J-P Jaudon, J-G KreskenJohn Rush, A.K. Barrett, S L Rosenthal, B.A.C. Saunders, I Ljungvall, M Deinert, E Bomassi, A H Estrada, M J Fernandez Del Palacio, N S Moise, J A Abbott, Y Fujii, A Spier, M W Luethy, R A Santilli, M Uechi, A Tidholm, C Schummer, Poppy Watson

Research output: Contribution to journal › Article › Academic › peer-review

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 (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.

Original language	English
Pages (from-to)	72-85
Journal	Journal of Veterinary Internal Medicine
Volume	32
Issue number	1
DOIs	https://doi.org/10.1111/jvim.14885
Publication status	Published - Jan 2018

Keywords

Cardiology
Cardiovascular
Echocardiography
Endocardiosis
Heart Failure
Mitral regurgitation

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Boswood, A., Gordon-McKeon, S., Häggström, J., Wess, G., Stepien, R. L., Oyama, M. A., Keene, B. W., Bonagura, J., MacDonald, K. A., Patteson, M., Smith, S., Fox, P. R., Sanderson, K., Woolley, S. R., Szatmári, V., Menaut, P., Church, W. M., O'Sullivan, M. L., Jaudon, J.-P., ... 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), 72-85. https://doi.org/10.1111/jvim.14885

@article{043ea259f36f45b6b68b1af58f21e5dd,

title = "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",

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 (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",

author = "A Boswood and Shauna Gordon-McKeon and J H{\"a}ggstr{\"o}m and G Wess and Stepien, {R L} and Oyama, {M A} and Keene, {B W} and J Bonagura and MacDonald, {K A} and M Patteson and S Smith and Fox, {P R} and K Sanderson and S.R. Woolley and V Szatm{\'a}ri and P Menaut and Church, {W M} and O'Sullivan, {M L} and J-P Jaudon and J-G Kresken and John Rush and A.K. Barrett and Rosenthal, {S L} and B.A.C. Saunders and I Ljungvall and M Deinert and E Bomassi and Estrada, {A H} and {Fernandez Del Palacio}, {M J} and Moise, {N S} and Abbott, {J A} and Y Fujii and A Spier and Luethy, {M W} and Santilli, {R A} and M Uechi and A Tidholm and C Schummer and Poppy Watson",

note = "Copyright {\textcopyright} 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.",

year = "2018",

month = jan,

doi = "10.1111/jvim.14885",

language = "English",

volume = "32",

pages = "72--85",

journal = "Journal of Veterinary Internal Medicine",

issn = "0891-6640",

publisher = "Wiley-Blackwell",

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Boswood, A, Gordon-McKeon, S, Häggström, J, Wess, G, Stepien, RL, Oyama, MA, Keene, BW, Bonagura, J, MacDonald, KA, Patteson, M, Smith, S, Fox, PR, Sanderson, K, Woolley, SR, Szatmári, V, Menaut, P, Church, WM, O'Sullivan, ML, Jaudon, J-P, Kresken, J-G, Rush, J, Barrett, AK, Rosenthal, SL, Saunders, BAC, Ljungvall, I, Deinert, M, Bomassi, E, Estrada, AH, Fernandez Del Palacio, MJ, Moise, NS, Abbott, JA, Fujii, Y, Spier, A, Luethy, MW, Santilli, RA, Uechi, M, Tidholm, A, Schummer, C & 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, vol. 32, no. 1, pp. 72-85. https://doi.org/10.1111/jvim.14885

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; Gordon-McKeon, Shauna; Häggström, J et al.
In: Journal of Veterinary Internal Medicine, Vol. 32, No. 1, 01.2018, p. 72-85.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - Longitudinal Analysis of Quality of Life, Clinical, Radiographic, Echocardiographic, and Laboratory Variables in Dogs with Preclinical Myxomatous Mitral Valve Disease Receiving Pimobendan or Placebo

T2 - The EPIC Study

AU - Boswood, A

AU - Gordon-McKeon, Shauna

AU - Häggström, J

AU - Wess, G

AU - Stepien, R L

AU - Oyama, M A

AU - Keene, B W

AU - Bonagura, J

AU - MacDonald, K A

AU - Patteson, M

AU - Smith, S

AU - Fox, P R

AU - Sanderson, K

AU - Woolley, S.R.

AU - Szatmári, V

AU - Menaut, P

AU - Church, W M

AU - O'Sullivan, M L

AU - Jaudon, J-P

AU - Kresken, J-G

AU - Rush, John

AU - Barrett, A.K.

AU - Rosenthal, S L

AU - Saunders, B.A.C.

AU - Ljungvall, I

AU - Deinert, M

AU - Bomassi, E

AU - Estrada, A H

AU - Fernandez Del Palacio, M J

AU - Moise, N S

AU - Abbott, J A

AU - Fujii, Y

AU - Spier, A

AU - Luethy, M W

AU - Santilli, R A

AU - Uechi, M

AU - Tidholm, A

AU - Schummer, C

AU - Watson, Poppy

PY - 2018/1

Y1 - 2018/1

N2 - 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.

AB - 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.

KW - Cardiology

KW - Cardiovascular

KW - Echocardiography

KW - Endocardiosis

KW - Heart Failure

KW - Mitral regurgitation

U2 - 10.1111/jvim.14885

DO - 10.1111/jvim.14885

M3 - Article

C2 - 29214723

SN - 0891-6640

VL - 32

SP - 72

EP - 85

JO - Journal of Veterinary Internal Medicine

JF - Journal of Veterinary Internal Medicine

IS - 1

ER -

Boswood A, Gordon-McKeon S, Häggström J, Wess G, Stepien RL, Oyama MA et al. 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. 2018 Jan;32(1):72-85. doi: 10.1111/jvim.14885