{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T04:51:54Z","timestamp":1773982314434,"version":"3.50.1"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T00:00:00Z","timestamp":1770076800000},"content-version":"vor","delay-in-days":2531,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2018,12,18]],"date-time":"2018-12-18T00:00:00Z","timestamp":1545091200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009449","name":"Petplan Charitable Trust","doi-asserted-by":"publisher","award":["2000.RES.2851"],"award-info":[{"award-number":["2000.RES.2851"]}],"id":[{"id":"10.13039\/100009449","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009449","name":"Petplan Charitable Trust","doi-asserted-by":"publisher","award":["2000.RES.2851"],"award-info":[{"award-number":["2000.RES.2851"]}],"id":[{"id":"10.13039\/100009449","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Factors associated with disease progression in dogs with preclinical (stage B) degenerative mitral valve disease (DMVD) have not been evaluated previously in primary care veterinary practice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To evaluate whether plasma cardiac biomarkers, clinical signs, and physical examination findings are associated with clinical progression (reaching the composite endpoint of initiation of treatment with a potent diuretic or cardiac death) in dogs presumed to have stage B DMVD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Animals<\/jats:title>\n                    <jats:p>Six-hundred and eighty-four dogs diagnosed with DMVD recruited from 73 primary care practices in the United Kingdom. Dogs were not receiving potent diuretics at recruitment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Prospective cohort study design. Primary care veterinarians recorded the presence or absence of clinical signs and physical examination findings. Baseline plasma N-terminal pro B-type natriuretic peptide (NT-proBNP) and cardiac troponin I were measured. Cox regression models measured associations between risk factor variables and clinical progression. Flexible parametric models generated predicted probabilities of reaching the composite endpoint for dogs with different combinations of prognostic risk factor variables.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Plasma NT-proBNP, heart rate, heart murmur intensity, presence of a cough, being a Cavalier King Charles Spaniel, and being prescribed pimobendan were associated with clinical progression to initiation of treatment with a potent diuretic or cardiac-related death.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Clinical Importance<\/jats:title>\n                    <jats:p>Dogs with stage B DMVD identified as having a high risk of disease progression might benefit from more frequent monitoring or further diagnostic evaluation. The prognostic factors identified could facilitate risk stratification of dogs presenting with preclinical DMVD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jvim.15390","type":"journal-article","created":{"date-parts":[[2018,12,19]],"date-time":"2018-12-19T00:15:16Z","timestamp":1545178516000},"page":"445-454","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Factors associated with disease progression in dogs with presumed preclinical degenerative mitral valve disease attending primary care veterinary practices in the United Kingdom"],"prefix":"10.1093","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0346-3767","authenticated-orcid":false,"given":"Madeleine J.","family":"Mattin","sequence":"first","affiliation":[{"name":"Royal Veterinary College, University of London , London,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5628-4194","authenticated-orcid":false,"given":"David C.","family":"Brodbelt","sequence":"additional","affiliation":[{"name":"Royal Veterinary College, University of London , London,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David B.","family":"Church","sequence":"additional","affiliation":[{"name":"Royal Veterinary College, University of London , London,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1795-4364","authenticated-orcid":false,"given":"Adrian","family":"Boswood","sequence":"additional","affiliation":[{"name":"Royal Veterinary College, University of London , London,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2019,3,1]]},"reference":[{"key":"2026020922223935600_jvim15390-bib-0001","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.1111\/j.1939-1676.2009.0392.x","article-title":"Guidelines for the diagnosis and treatment of canine chronic valvular heart disease","volume":"23","author":"Atkins","year":"2009","journal-title":"J Vet Intern Med"},{"key":"2026020922223935600_jvim15390-bib-0002","doi-asserted-by":"crossref","first-page":"1765","DOI":"10.1111\/jvim.14586","article-title":"Effect of pimobendan in dogs with preclinical myxomatous mitral valve disease and cardiomegaly: the EPIC study\u2014a randomized clinical trial","volume":"30","author":"Boswood","year":"2016","journal-title":"J Vet Intern Med"},{"key":"2026020922223935600_jvim15390-bib-0003","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.jvc.2012.01.008","article-title":"Prediction of first onset of congestive heart failure in dogs with degenerative mitral valve disease: the PREDICT cohort study","volume":"14","author":"Reynolds","year":"2012","journal-title":"J Vet Cardiol"},{"key":"2026020922223935600_jvim15390-bib-0004","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1111\/j.1939-1676.2009.0347.x","article-title":"Association of plasma N-terminal pro-B-type natriuretic peptide concentration with mitral regurgitation severity and outcome in dogs with asymptomatic degenerative mitral valve disease","volume":"23","author":"Chetboul","year":"2009","journal-title":"J Vet Intern Med"},{"key":"2026020922223935600_jvim15390-bib-0005","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1111\/j.1939-1676.2011.00860.x","article-title":"Survival characteristics and prognostic variables of dogs with preclinical chronic degenerative mitral valve disease attributable to myxomatous degeneration","volume":"26","author":"Borgarelli","year":"2012","journal-title":"J Vet Intern Med"},{"key":"2026020922223935600_jvim15390-bib-0006","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.jvc.2014.05.001","article-title":"Increased NT-proANP predicts risk of congestive heart failure in Cavalier King Charles spaniels with mitral regurgitation caused by myxomatous valve disease","volume":"16","author":"Eriksson","year":"2014","journal-title":"J Vet Cardiol"},{"key":"2026020922223935600_jvim15390-bib-0007","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1111\/j.1939-1676.2002.tb01610.x","article-title":"Efficacy of enalapril for prevention of congestive heart failure in dogs with myxomatous valve disease and asymptomatic mitral regurgitation","volume":"16","author":"Kvart","year":"2002","journal-title":"J Vet Intern Med"},{"key":"2026020922223935600_jvim15390-bib-0008","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.jvc.2012.01.007","article-title":"Retrospective review of carvedilol administration in 38 dogs with preclinical chronic valvular heart disease","volume":"14","author":"Gordon","year":"2012","journal-title":"J Vet Cardiol"},{"key":"2026020922223935600_jvim15390-bib-0009","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1016\/j.cvsm.2013.07.010","article-title":"Using cardiac biomarkers in veterinary practice","volume":"43","author":"Oyama","year":"2013","journal-title":"Vet Clin North Am Small Anim Pract"},{"key":"2026020922223935600_jvim15390-bib-0010","article-title":"Prognostic factors in dogs with presumed degenerative mitral valve disease attending primary-care veterinary practices in the United Kingdom","author":"Mattin","year":"2018","journal-title":"J Vet Intern Med"},{"key":"2026020922223935600_jvim15390-bib-0011","doi-asserted-by":"crossref","first-page":"1358","DOI":"10.1111\/j.1939-1676.2010.0592.x","article-title":"Detection of congestive heart failure in dogs by Doppler echocardiography","volume":"24","author":"Schober","year":"2010","journal-title":"J Vet Intern Med"},{"key":"2026020922223935600_jvim15390-bib-0012","author":"VetCompass","year":"2018"},{"key":"2026020922223935600_jvim15390-bib-0013","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1016\/j.cvsm.2010.03.008","article-title":"Canine degenerative myxomatous mitral valve disease: natural history, clinical presentation and therapy","volume":"40","author":"Borgarelli","year":"2010","journal-title":"Vet Clin North Am Small Anim Pract"},{"key":"2026020922223935600_jvim15390-bib-0014","article-title":"Veterinary Epidemiologic Research","author":"Dohoo","year":"2009","edition":"2"},{"key":"2026020922223935600_jvim15390-bib-0015","article-title":"Stata: Release 14. Statistical Software","author":"StataCorp","year":"2013"},{"key":"2026020922223935600_jvim15390-bib-0016","doi-asserted-by":"crossref","first-page":"2175","DOI":"10.1002\/sim.1203","article-title":"Flexible parametric proportional-hazards and proportional-odds models for censored survival data, with application to prognostic modelling and estimation of treatment effects","volume":"21","author":"Royston","year":"2002","journal-title":"Stat Med"},{"key":"2026020922223935600_jvim15390-bib-0017","first-page":"xxvi","article-title":"Flexible Parametric Survival Analysis Using Stata: Beyond the Cox Model","author":"Royston","year":"2011"},{"key":"2026020922223935600_jvim15390-bib-0018","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1177\/1536867X0900900206","article-title":"Further development of flexible parametric models for survival analysis","volume":"9","author":"Lambert","year":"2009","journal-title":"Stata J"},{"key":"2026020922223935600_jvim15390-bib-0019","article-title":"Modelling survival data in medical research","author":"Collett","year":"2003","edition":"2"},{"key":"2026020922223935600_jvim15390-bib-0020","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.jvc.2016.11.001","article-title":"Biologic variability of N-terminal pro-brain natriuretic peptide in healthy dogs and dogs with myxomatous mitral valve disease","volume":"19","author":"Winter","year":"2017","journal-title":"J Vet Cardiol"},{"key":"2026020922223935600_jvim15390-bib-0021","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1111\/j.1939-1676.2012.00894.x","article-title":"The combined prognostic potential of serum high-sensitivity cardiac troponin I and N-terminal pro-B-type natriuretic peptide concentrations in dogs with degenerative mitral valve disease","volume":"26","author":"Hezzell","year":"2012","journal-title":"J Vet Intern Med"},{"key":"2026020922223935600_jvim15390-bib-0022","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1111\/vcp.12268","article-title":"Biologic variability in NT-proBNP and cardiac troponin-I in healthy dogs and dogs with mitral valve degeneration","volume":"44","author":"Ruaux","year":"2015","journal-title":"Vet Clin Pathol"},{"key":"2026020922223935600_jvim15390-bib-0023","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1111\/j.1476-4431.2007.00241.x","article-title":"Serum concentrations of cardiac troponin I and cardiac troponin T in dogs with class IV congestive heart failure due to mitral valve disease","volume":"17","author":"Linklater","year":"2007","journal-title":"J Vet Emerg Crit Care (San Antonio)"},{"key":"2026020922223935600_jvim15390-bib-0024","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1111\/j.1939-1676.2008.0150.x","article-title":"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","volume":"22","author":"Haggstrom","year":"2008","journal-title":"J Vet Intern Med"},{"key":"2026020922223935600_jvim15390-bib-0025","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1111\/j.1939-1676.2007.0008.x","article-title":"Survival characteristics and prognostic variables of dogs with mitral regurgitation attributable to myxomatous valve disease","volume":"22","author":"Borgarelli","year":"2008","journal-title":"J Vet Intern Med"},{"key":"2026020922223935600_jvim15390-bib-0026","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1292\/jvms.64.1023","article-title":"Heart rate modulation by sympathetic nerves in dogs with heart failure","volume":"64","author":"Uechi","year":"2002","journal-title":"J Vet Med Sci"},{"key":"2026020922223935600_jvim15390-bib-0027","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.beproc.2016.04.015","article-title":"Heart rate variability predicts the emotional state in dogs","volume":"128","author":"Katayama","year":"2016","journal-title":"Behav Processes"},{"key":"2026020922223935600_jvim15390-bib-0028","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1111\/jvim.12311","article-title":"Longitudinal electrocardiographic evaluation of dogs with degenerative mitral valve disease","volume":"28","author":"Lopez-Alvarez","year":"2014","journal-title":"J Vet Intern Med"},{"key":"2026020922223935600_jvim15390-bib-0029","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1111\/jsap.12079","article-title":"Relationships between heart rate and age, bodyweight and breed in 10,849 dogs","volume":"54","author":"Hezzell","year":"2013","journal-title":"J Small Anim Pract"},{"key":"2026020922223935600_jvim15390-bib-0030","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1111\/j.1939-1676.1995.tb03276.x","article-title":"Heart sounds and murmurs: changes related to severity of chronic valvular disease in the Cavalier King Charles spaniel","volume":"9","author":"Haggstrom","year":"1995","journal-title":"J Vet Intern Med"},{"key":"2026020922223935600_jvim15390-bib-0031","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1111\/jsap.12265","article-title":"Murmur intensity in small-breed dogs with myxomatous mitral valve disease reflects disease severity","volume":"55","author":"Ljungvall","year":"2014","journal-title":"J Small Anim Pract"},{"key":"2026020922223935600_jvim15390-bib-0032","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1111\/jvim.12544","article-title":"Clinical severity score system in dogs with degenerative mitral valve disease","volume":"29","author":"Lopez-Alvarez","year":"2015","journal-title":"J Vet Intern Med"},{"key":"2026020922223935600_jvim15390-bib-0033","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1111\/j.1939-1676.1999.tb02166.x","article-title":"Auscultation in mild mitral regurgitation in dogs: observer variation, effects of physical maneuvers, and agreement with color Doppler echocardiography and phonocardiography","volume":"13","author":"Pedersen","year":"1999","journal-title":"J Vet Intern Med"},{"key":"2026020922223935600_jvim15390-bib-0034","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1111\/jvim.12039","article-title":"Risk factors for coughing in dogs with naturally acquired myxomatous mitral valve disease","volume":"27","author":"Ferasin","year":"2013","journal-title":"J Vet Intern Med"},{"key":"2026020922223935600_jvim15390-bib-0035","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1111\/j.1748-5827.2009.00889.x","article-title":"N-terminal pro B-type natriuretic peptide and left ventricular diameter independently predict mortality in dogs with mitral valve disease","volume":"51","author":"Moonarmart","year":"2010","journal-title":"J Small Anim Pract"},{"key":"2026020922223935600_jvim15390-bib-0036","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.jvc.2005.10.001","article-title":"Retrospective study of 942 small-sized dogs: prevalence of left apical systolic heart murmur and left-sided heart failure, critical effects of breed and sex","volume":"8","author":"Serfass","year":"2006","journal-title":"J Vet Cardiol"},{"key":"2026020922223935600_jvim15390-bib-0037","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.jvc.2012.01.006","article-title":"Myxomatous mitral valve disease in dogs: does size matter?","volume":"14","author":"Parker","year":"2012","journal-title":"J Vet Cardiol"},{"key":"2026020922223935600_jvim15390-bib-0038","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1038\/ki.2008.328","article-title":"Survival analysis: time-dependent effects and time-varying risk factors","volume":"74","author":"Dekker","year":"2008","journal-title":"Kidney Int"},{"key":"2026020922223935600_jvim15390-bib-0039","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1136\/vr.102818","article-title":"Variation in the management of congestive cardiac failure in dogs","volume":"176","author":"Davies","year":"2015","journal-title":"Vet Rec"},{"key":"2026020922223935600_jvim15390-bib-0040","doi-asserted-by":"crossref","first-page":"i","DOI":"10.1136\/vr.j540","article-title":"Ten-minute chat","volume":"180","author":"Boswood","year":"2017","journal-title":"Vet Rec"}],"container-title":["Journal of Veterinary Internal Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjvim.15390","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jvim.15390","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/jvim.15390","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/jvim\/article-pdf\/33\/2\/445\/66659531\/jvim15390.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jvim\/article-pdf\/33\/2\/445\/66659531\/jvim15390.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T03:33:01Z","timestamp":1770694381000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jvim\/article\/33\/2\/445\/8448092"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,3,1]]},"references-count":40,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2019,3,1]]}},"URL":"https:\/\/doi.org\/10.1111\/jvim.15390","relation":{},"ISSN":["1939-1676"],"issn-type":[{"value":"1939-1676","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2019,3]]},"published":{"date-parts":[[2019,3,1]]},"assertion":[{"value":"2018-03-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-11-15","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-12-18","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}