Skip to main content
SpringerLink
Log in

Database development and survival analysis in a clinical and historical cohort of dogs affected by myxomatous mitral valve disease treated or not with pimobendan using causal inference techniques

  • Original Article
  • Published:
Veterinary Research Communications Aims and scope Submit manuscript

Abstract

The aim of this work was to retrospectively evaluate the influence of pimobendan on the survival time (ST) of dogs with myxomatous mitral valve disease at different stages using an Inverse Probability Weighting (IPW) analysis. An IPW method was used to minimize confounding and IPW weighted time-repeated logistic model was used to approximate survival curves (SCs) and calculate survival differences. Subjects were allocated into exposed (E) and unexposed (U). Dogs in the American College of Veterinary Internal Medicine (ACVIM) B2 class treated with pimobendan (± ACE-inhibitors) were selected for the E group, as well as symptomatic patients (ACVIM class C) treated with triple (furosemide, ACE-inhibitor, pimobendan) or quadruple (furosemide, ACE-inhibitor, pimobendan and spironolactone) therapy. The U group included ACVIM class B2 dogs not treated with any medication and ACVIM C dogs treated with a combination of furosemide and ACE-inhibitor/spironolactone without pimobendan. The survival curve (SC) of the E group crossed the U group at 1634 days. The difference between the two SCs at the time of maximum survival difference in favor of the U group was 11.3% (CI 1.7%–20.9%) (significant), in favor of the E group was 3.9% (CI -8.6%–16.4%) (not significant) and at the mean ST was 3.6% (CI -8.5%–15.7%) (not significant) in favor of the E group. For times greater than 1634 days the survival was in favor of the E group, but there were no statistically significant differences in survival in favor of the E group in this clinical population.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Data availability

Data is available by upon request.

Code availability

Not applicable.

References

  • Acierno MJ, Brown S, Coleman AE, Jepson RE, Papich M, Stepien RL, Syme HM (2018) ACVIM consensus statement: guidelines for the identification, evaluation, and management of systemic hypertension in dogs and cats. J Vet Intern Med 32:1803–1822

    Article  Google Scholar 

  • Boyle KL, Leech E (2012) A review of the pharmacology and clinical uses of pimobendan. J Vet Emerg Crit Care (San Antonio) 22(4):398–408

    Article  Google Scholar 

  • Borgarelli M, Crosara S, Lamb K, Savarino P, La Rosa G, Tarducci A, Häggström J (2012) Survival characteristics and prognostic variables of dogs with preclinical chronic degenerative mitral valve disease attributable to Myxomatous degeneration. J Vet Intern Med 26(1):69–75

    Article  CAS  Google Scholar 

  • Borgarelli M, Abbott J, Braz-Ruivo L, Chiavegato D, Crosara S, Lamb K, Ljungvall I, Poggi M, Santilli RA, Häggström J (2015) Prevalence and prognostic importance of pulmonary hypertension in dogs with myxomatous mitral valve disease. J Vet Intern Med 29(2):569–574

    Article  CAS  Google Scholar 

  • Boswood A, Häggström J, Gordon SG, Wess G, Stepien RL, Oyama MA, Keene BW, Bonagura J, MacDonald KA, Patteson M, Smith S, Fox PR, Sanderson K, Woolley R, Szatmari V, Menaut P, Church WM, O’Sullivan ML, Jaudon J-P et al (2016) Effect of Pimobendan in dogs with preclinical Myxomatous mitral valve disease and cardiomegaly: the EPIC study-a randomized clinical trial. J Vet Intern Med 30:1765–1779

    Article  CAS  Google Scholar 

  • Cole SR, Hernán MA (2008) Constructing inverse probability weights for marginal structural models. Am J Epidemiol 168:656–664. https://doi.org/10.1093/aje/kwn164

    Article  PubMed  PubMed Central  Google Scholar 

  • Cornell CC, Kittleson MD, Della Torre P, Häggström J, Lombard CW, Pedersen HD, Vollmar A, Wey A (2004) Allometric scaling of M-mode cardiac measurements in Normal adult dogs. J Vet Intern Med 18:311–321

    Article  Google Scholar 

  • Häggström J, Boswood A, O’Grady M, Jons O, Smith S, Swift S, Borgarelli M, Gavaghan B, Kresken JG, Patteson M, Ablad B, Bussadori CM, Glaus T, Kovacevic A, Rapp M, Santilli RA, Tidholm A, Eriksson A, Belanger MC et al (2008) Effect of pimobendan or benazepril hydrochloride on survival times in dogs with congestive heart failure caused by naturally occurring myxomatous mitral valve disease: the QUEST study. J Vet Intern Med 22:1124–1135

    Article  Google Scholar 

  • Hansson K, Häggström J, Kvart C, Lord P (2002) Left atrial to aortic root indices using two-dimensional and m-mode echocardiography in cavalier king Charles spaniels with and without left atrial enlargement. Vet Radiol Ultrasound 43:568–575

    Article  Google Scholar 

  • Hernán MA, Brumback B, Robins JM (2001) Marginal structural models to estimate the joint causal effect of nonrandomized treatments. J Am Stat Assoc 96:440–448. https://doi.org/10.1198/016214501753168154

    Article  Google Scholar 

  • Hernán MA, Robins JM (2020) Causal Inference: What If

  • Imagawa J, Satoh K, Taira N (1987) Cardiac and coronary vasodilator profile of pimobendan, a new cardiotonic drug, revealed by use of isolated, blood-perfused dog heart preparations. Heart Vessel 3(4):182–189

    Article  CAS  Google Scholar 

  • International Small Animal Cardiac Health Council (1994) Recommendations for the diagnosis and treatment of heart failure in small animals. ISACHC Publication, Woodbridge, p 5

  • Kassambara A, Kosinski M, Biecek P (2020) Survminer: drawing survival curves using “ggplot2”

  • Keene BW, Atkins CE, Bonagura JD, Fox PR, Häggström J, Fuentes VL, Oyama MA, Rush JE, Stepien R, Uechi M (2019) ACVIM consensus guidelines for the diagnosis and treatment of myxomatous mitral valve disease in dogs. J Vet Intern Med 33:1127–1140

    Article  Google Scholar 

  • Kim HT, Han SM, Song WJ, Kim B, Choi M, Yoon J, Youn HY (2017) Retrospective study of degenerative mitral valve disease in small-breed dogs: survival and prognostic variables. J Vet Sci 18(3):369–376

    Article  Google Scholar 

  • Lüdecke D, Ben-Shachar MS, Patil I, Makowski D (2020) Extracting, computing and exploring the parameters of statistical models using {R}. J Open Source Softw 5:2445. https://doi.org/10.21105/joss.02445

    Article  Google Scholar 

  • Mattin MJ, Boswood A, Church DB, Brodbelt DC (2018) Prognostic factors in dogs with presumed degenerative mitral valve disease attending primary-care veterinary practices in the United Kingdom. J Vet Intern Med 33(2):432–444

    Article  Google Scholar 

  • Mahto A (2019) Splitstackshape: stack and reshape datasets after splitting concatenated values

  • R Core Team (2014) R: a language and environment for statistical computing

  • Summerfield NJ, Boswood A, O'Grady MR, Gordon SG, Dukes-McEwan J, Oyama MA, Smith S, Patteson M, French AT, Culshaw GJ, Braz-Ruivo L, Estrada A, O'Sullivan ML, Loureiro J, Willis R, Watson P (2012) Efficacy of pimobendan in the prevention of congestive heart failure or sudden death in Doberman pinschers with preclinical dilated cardiomyopathy (the PROTECT study). J Vet Intern Med Nov-Dec 26(6):1337–1349

    Article  CAS  Google Scholar 

  • Teichholz LE, Kreulen T, Herman MV, Gorlin R (1976) Problems in echocardiographic volume determinations: echocardiographic-angiographic correlations in the presence of absence of asynergy. Am J Cardiol 37:7–1

    Article  CAS  Google Scholar 

  • Thomas WP, Gaber CE, Jacobs GJ, Kaplan PM, Lombard CW, Moise NS, Moses BL (1993) Recommendations for standards in transthoracic two-dimensional echocardiography in the dog and cat. Echocardiography Committee of the Specialty of cardiology, American College of Veterinary Internal Medicine. J Vet Intern Med 7:247–252

    Article  CAS  Google Scholar 

  • Wickham H (2016) ggplot2: elegant graphics for data analysis. Springer-Verlag, New York

    Book  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Veterinary Medicine, University of Milan, Lodi, Italy

    Mara Bagardi, Chiara Locatelli, Fabio Maria Colombo & Paola G. Brambilla

  2. Anderson Moores Veterinary Specialists, The Granary, Bunstead Barns, Poles Lane, Hursley, Winchester, Hampshire, SO21 2LL, UK

    Valentina Palermo

  3. Centre for Pharmacoepidemiology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden

    Laura Pazzagli

Authors
  1. Mara Bagardi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Valentina Palermo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Chiara Locatelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Fabio Maria Colombo
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Laura Pazzagli
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Paola G. Brambilla
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Conceptualization and experimental design, P.G.B, V.P., M.B., F.M.C. and L.P.; methodology, V.P., M.B., F.M.C. and L.P.; data curation, V.P. and M.B.; software, F.M.C.; formal analysis, F.M.C. and M.B.; investigation, F.MC., M.B., L.P. and P.G.B.; resources, P.G.B.; writing—original draft, M.B., F.M.C., V.P., L.P. and P.G.B.; writing—review and editing, M.B., V.P., C.L., F.M.C., L.P. and P.G.B; supervision, P.G.B. and L.P; project administration, P.G.B. All authors have read and agreed to the published version of the manuscript.

Corresponding author

Correspondence to Mara Bagardi.

Ethics declarations

Ethics approval

Not applicable.

Consent to participate

Not applicable.

Consent for publication

Not applicable.

Conflicts of interest/competing interests

Not applicable.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bagardi, M., Palermo, V., Locatelli, C. et al. Database development and survival analysis in a clinical and historical cohort of dogs affected by myxomatous mitral valve disease treated or not with pimobendan using causal inference techniques. Vet Res Commun 46, 481–486 (2022). https://doi.org/10.1007/s11259-021-09875-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11259-021-09875-3

Keywords

Search

Navigation