‘a small breed dog with a heart murmur – should I start pimobendan?’
Dr Joao Neves
VVS Cardiology Specialist
Dr Joao Neves discusses the usefulness and limitations of murmur intensity in managing pre-clinical stages of mitral valve disease.
Myxomatous mitral valve disease (MMVD) is a common cardiac disease in dogs, with prevalence of up to 3.54%. Smaller breeds and males are much more predisposed to this condition with Cavalier King Charles Spaniels, King Charles Spaniels, Whippets, Poodles, Yorkshire Terriers, Shih Tzus and Chihuahuas the top 7 breeds with the highest risk of having MMVD in the UK.
According to the ACVIM Consensus, the pre-clinical stage B, indicating the presence of disease, but without current or past signs of congestive heart failure, can be subdivided in two stages – B1 and B2. In stage B1 there is no left atrial or ventricular enlargement, and in stage B2 there is both left atrial and ventricular enlargement. Whereas a few years ago the discrimination between the pre-clinical phases B1 and B2 was not crucial from a therapy point-of-view, the recent EPIC study has now changed this. This prospective study showed that preclinical mitral valve disease patients with both left atrial and ventricular enlargement (B2) benefit from starting pimobendan, this prolongs the time to the onset of heart failure by an average of 15 months!
According to the EPIC trial the distinction between stage B1 and B2 should be based on a combination of the intensity of the heart murmur, left atrial and ventricular echocardiographic dimensions, and thoracic radiographs. It is well-accepted that echocardiography is the most important and most accurate tool to identify left atrial and ventricular enlargement. Thoracic radiographs, if used alone with heart murmur grade, are not as sensitive to detect any left atrioventricular dilation, and this can result in some patients that would benefit from starting pimobendan being missed.
A common question raised by owners is whether their pet, now diagnosed with Stage B1 MMVD, should start pimobendan straight away, rather than monitoring and re-staging the patient with echocardiography every 6-12 months. However currently, starting pimobendan before stage B2 is not recommended by the ACVIM Consensus as there is no evidence that this medication brings any benefit if started earlier. Additionally, a previous study showed that only 4% of patients in the B1 phase progressed into stage B2 during the observation period, which was two years or more, in most of the patients. This means that that patients in B1 can remain in stage B1 for many years without needing pimobendan. If pimobendan is started in patients before they progress to stage B2, this could carry a high unnecessarily cost for the owners. In addition, there is a French study that suggests pimobendan administration could cause undesirable side effects in dogs with early asymptomatic mitral valve disease. There are also two reported cases, and additional anecdotal reports, of left ventricular hypertrophy caused by pimobendan in dogs without left atrial dilation.
If repeat echocardiography is not an option, for whatever reason, it is possible to use thoracic radiographs in patients in stage B1 as an alternative. The ACVIM consensus suggests the use of two radiographic indexes if echocardiography cannot be performed – the well-known vertebral heart score (VHS), and the more recently proposed vertebral left atrial score (VLAS). The Consensus states that a VHS ≥ 11.5 (or above the breed-specific proposed VHS) or a VLAS ≥ 3 likely identifies Stage B2 patients. However, a more recent study proposed lower cut-offs, VHS > 11 and VLAS > 2.3.
It is important when communicating with your patient’s owners to explain that radiography is not as accurate at identifying stage B2 patients as echocardiography. For example, 3 out of 10 dogs with VHS < 11 will be wrongly classified as a stage B1 (rather than B2). Another limitation of these radiographic indexes is that the clinician should be confident and competent in measuring them accurately, as incorrect measurements may contribute to inappropriate clinical decisions.
In summary the use of echocardiography is highly recommended to decide whether a pre-clinical mitral valve disease patient would benefit from pimobendan or not.
In some patients where there are financial barriers to echocardiography, or other diagnostics, the intensity of the heart murmur can also be useful to assess the likelihood that the patient would benefit from the introduction of pimobendan. According to a 2004 study, an adult/geriatric small dog with a ‘soft’ (grade I-II/VI) left apical systolic heart murmur has a 90% probability of being in stage B1. Although this study used slightly different criteria to differentiate stage B1 from stage B2 than those currently recommended by the ACVIM consensus, the key message is that most small adult/geriatric dogs with a soft left apical murmur probably don’t need pimobendan yet.
Although it may seem ‘safe’ to use the presence of a soft left apical systolic murmur to identify mitral valve disease patients in stage B1, this should be used as a last resort. As, of course, this study also highlights that 1 in 10 of these patients would actually benefit from starting pimobendan. Therefore, echocardiography should always be recommended to identify the 10% that are already in stage B2 and that would require pimobendan.
It is important to note that it is not possible to assess the likelihood that the patient would benefit from the introduction of pimobendan in cases where the murmur is moderate (grade III-IV) or loud (grade IV-VI). These patients can be either in stage B1, B2, C or D (i.e. 20 % of patients with loud murmur may not require yet pimobendan). However, 95% of patients with a loud murmur with a precordial thrill are at least in stage B2 and, therefore, do require pimobendan.
Moreover, care is required to avoid extrapolating the results from this 2004 study to dogs larger than 20kg. Larger dogs can have soft murmurs due to DCM (rather than mitral valve disease) and these patients would require pimobendan. More importantly, the differentiation between a grade II (soft) and grade III (moderate) heart murmur is somewhat subjective and a misclassification of the heart murmur intensity can lead to an inappropriate clinical decision.
In conclusion, we know that starting pimobendan in patients with stage B2 MMVD prolongs the time to the onset of heart failure by an average of 15 months. Echocardiography should always be recommended in dogs with a left apical systolic murmur, even if the murmur is soft. Radiographs and, as a last resort, the intensity of the heart murmur, can be useful, but the owner should be informed about the consequences that can result from falsely staging a B2 as a B1.
Clinical cases can feel overwhelming to deal with in general practice, but VVS’ friendly world-class specialists are on hand to support you and to enable you to bring outstanding clinical care to your patients and reassurance to their owners. Seamless multi-disciplinary support from our cardiology, internal medicine and other specialist teams is available to you for patients, so you feel supported throughout as the case progresses.
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Borgareli et al., Survival Characteristics and Prognostic Variables of Dogs with Preclinical Chronic Degenerative Mitral Valve Disease Attributable to Myxomatous Degeneration, JVIM 2011
Boswood et al., Effect of Pimobendan in Dogs with Preclinical Myxomatous Mitral Valve Disease and Cardiomegaly: The EPIC Study-A Randomized Clinical Trial, JVIM 2016
Keene et al., ACVIM consensus guidelines for the diagnosis and treatment of myxomatous mitral valve disease in dogs, JVIM 2019
Levicar et al., Comparison of different radiographic scores with associated echocardiographic measurements and prediction of heart enlargement in dogs with and without myxomatous mitral valve disease, JVC 2022
Ljungvall et al., Murmur intensity in small-breed dogs with myxomatous mitral valve disease reflects disease severity, JSAP 2014