REVIEW

An update on treatment and prognostic indicators in canine myxomatous mitral valve disease Mitral regurgitation caused by myxomatous mitral valve disease is

INTRODUCTION

the most common cause for congestive heart failure and cardiacrelated mortality in dogs. Typically, it takes several years for the disease to progress from mild, clinically silent myxomatous mitral valve disease to severe disease with signs of congestive heart failure. A proportion of dogs will never progress into congestive heart failure before they die from other causes or old age. Some variables have been shown to be predictive of onset of congestive heart failure and they might be useful to identify dogs that need more frequent monitoring and eventually treatment. Results from several controlled clinical trials are available concerning medical treatment of dogs with myxomatous mitral valve disease with or without congestive heart failure. These trials provide estimates of treatment effects and also allow identification of other variables with prognostic value for the outcome after the onset of congestive heart failure. Use of prognostic variables together with qualitative and quantitative results from clinical drug trials may aid the clinician and owner to plan and decide on optimal management of the myxomatous mitral valve disease dog. The purpose of this article is to review the current knowledge of prognostic variables and therapy for this common condition in dogs.

J. HÄGGSTRÖM, K. HÖGLUND*

AND

M. BORGARELLI†

Journal of Small Animal Practice (2009) 50 (Suppl. 1). 25–33 DOI: 10.1111/j.1748-5827.2009.00800.x Accepted: 19th June 2009

Conflicts of Interest: MlB has received funding for research from Boehringer Ingelheim, Merial and Intervet, which was not related to this work; JH has received funding for research from Boehringer Ingelheim and acts as scientific advisor for Ceva Santé Animal and Orion Pharma, KH declares no conflicts of interest.

Department of Clinical Sciences, Faculty of Veterinary Medicine and Animal Sciences, Swedish University of Agricultural Sciences, Box 7054, 750 07 Uppsala, Sweden *Department of Anatomy, Physiology and Biochemistry, Faculty of Veterinary Medicine and Animal Sciences, Swedish University of Agricultural Sciences, Box 7011, 750 07 Uppsala, Sweden †College of Veterinary Medicine, Kansas State University, 1800 Anderson Avenue, 66506 Manhattan Kansas, USA Journal of Small Animal Practice

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Actuarial data shows mitral regurgitation (MR) caused by myxomatous mitral valve disease (MMVD) to be the major contributor to cardiovascular morbidity and mortality in dogs (Egenvall and others 2006). Myxomatous mitral valve disease is characterised by a chronic progression, with the condition worsening from mild to severe over years (Kvart and others 2002, Borgarelli and others 2008). Dogs with mild to moderate disease usually do not show outward clinical signs of cardiac disease, whereas dogs with severe MMVD and MR characterised by left atrial and left ventricular enlargement are at risk of developing signs of congestive heart failure (CHF). In dogs that have not progressed to CHF, the presence of MMVD may still cause problems by complicating elective surgical procedures or interventions, such as dental procedures, and by causing anxiety for the owner. Because MMVD is a chronic disease developing with age, only a proportion of dogs progress into CHF before dying of old age or other comorbid conditions. The exact proportion of dogs progressing into CHF is currently not known, but mild MMVD should be regarded as a relatively benign condition in dogs considering the natural history of the disease and the low risk for sudden death (Kvart and others 2002, Atkins and others 2007, Borgarelli and others 2008, Pouchelon and others 2008). Some dogs do develop CHF, and it is important to identify factors that may assist detection of dogs at risk. Dogs at risk need more intensive monitoring and owners should be educated on how to recognise the signs of CHF. In dogs that develop CHF, the signs are usually progressive. Although the majority of these dogs die or are euthanased within a year of the development of clinical signs (Ettinger and others 1998, The BENCH Study Group 1999, Borgarelli and others 2008, Häggström and others 2008), the survival time and quality of life vary considerably between

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J. Häggström and others

individuals. Furthermore, different types of CHF medication have been shown to influence the outcome in dogs with CHF caused by MMVD (Ettinger and others 1998, The BENCH Study Group 1999, Häggström and others 2008). Use of prognostic variables together with qualitative and quantitative results from clinical drug trials may aid the attending clinician and owner to plan and decide on optimal management of the dog with MMVD. The purpose of this article is to review the current knowledge of prognostic variables and therapy for this common condition in dogs.

INDICATORS FOR PROGRESSION OF MR AND DEVELOPMENT OF CHF Once mild MR caused by MMVD has been diagnosed in a dog, the question of long-term prognosis arises. It is well known that some breeds, such as Cavalier King Charles spaniel (CKCS), develop MMVD at a younger age than other breeds (Thrusfield and others 1985, Häggström and others 1992, Beardow and Buchanan 1993, Egenvall and others 2006). Within breeds where the inheritance of MMVD has been studied, the age of onset has been shown to be inherited as a polygenic threshold trait (Swenson and others 1996, Olsen and others 1999) and males develop the disease at a younger age than females (Häggström and others 1992, Pedersen and others 1999, Serfass and others 2006). However, to the best of the authors’ knowledge, it has never been shown that MMVD progresses differently between breeds or between males and females. Risk factors associated with rapid progression of mild MMVD include: age, degree of MR (as indicated by murmur intensity and/or jet size by colour Doppler echocardiography) and severity of valvular changes (Häggström and others 1992, Pedersen and others 1999, Olsen and others 2003, Borgarelli and others 2008). The severity of valvular changes include presence and degree of mitral valve prolapse (MVP), characterised by bulging of one or both valvular leaflets into the left atrium. Indeed, the disease progresses more rapidly in dogs with MR associated 26

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with MVP than those with MR alone (Pedersen and others 1999, Olsen and others 2003). The degree of leaflet thickening has also been shown to influence long-term prognosis (Pedersen and others 1999, Olsen and others 2003). Rupture of chordae tendineae has been reported to be a common feature of MMVD (Buchanan 1977, Beardow and Buchanan 1993). One study reported a comparably favourable long-term prognosis in dogs with ruptured chordae tendineae (Serres and others 2007). Presumably, most of the dogs in that study had rupture of minor chords because rupture of major chordae tendineae is generally considered to be associated with an acute increase of MR and a poor prognosis (Häggström and others 2005). It is of interest to identify variables that could predict time to onset of CHF in a dog diagnosed with MMVD and MR. The ideal prognostic variable would change linearly with time and allow a detailed estimation of when CHF could be expected. Unfortunately,

such a variable has yet to be identified. At present, the variables that have been shown most effective to predict the onset of CHF do not change dramatically (accelerate) until CHF is imminent or present. These variables include: echocardiographic variables, such as left atrial size [left atrial (LA) to aortic root (AO) ratio (LA/AO)], left vetricular end-diastolic and end-systolic size [percentage increase in LVIDd and LVIDs from expected values based on body weight (LVIDd inc. and LVIDs inc.), end-diastolic and end-systolic volume indices (EDV-I and ESV-I)], transmitral flow pattern [peak velocity of early transmitral filling (E-peak velocity)], vertebral heart score (VHS) obtained from thoracic radiographs, blood concentrations of natriuretic peptides (NT-proANP and NT-proBNP), heart rate and heart rate variability (Fig 1) (Häggström and others 1996b, Häggström and others 2000, Fujii and Wakao 2003, Kittleson and Brown 2003, Doxey and Boswood 2004, Spratt and others 2004, Boswood Hazard Ratio and 95% CI P1.2 m/sec (Y/N)

P30 ml/m2

P100 ml/m2 Bilateral MVP (Y/N) P140 mmHg (Y/N) Arrhythmia (Y/N)

P