Do we still believe that the EPIC study was helpful? When are we using pimobendan in dogs with mitral valve disease in early 2019?
Time has moved on a bit. We’ve had the benefit of a chance to reflect on EPIC:
J Vet Intern Med. 2016 Nov;30(6):1765-1779. doi: 10.1111/jvim.14586. Epub 2016 Sep 28.
Effect of Pimobendan in Dogs with Preclinical Myxomatous Mitral Valve Disease and Cardiomegaly: The EPIC Study-A Randomized Clinical Trial.
Boswood A et al.
https://onlinelibrary.wiley.com/doi/full/10.1111/jvim.14586
The biggest issue is the inclusion criteria. These were left atrial‐to‐aortic ratio ≥1.6, normalized left ventricular internal diameter in diastole ≥1.7, and vertebral heart sum >10.5.
It is, essentially, a no-brainer, that even under ideal conditions a VHS >10.5 is not necessarily abnormal for all individuals of all breeds.
It has also become increasingly evident that purely 2D echo measures of cardiac enlargement are relatively unreliable and that universal species-wide cut-offs are probably inappropriate. This is discussed in some depth in a very recent paper by Eva Larouche-Lebel and colleagues:
J Vet Intern Med. 2019 Feb 22. doi: 10.1111/jvim.15461. [Epub ahead of print]
Echocardiographic indices and severity of mitral regurgitation in dogs with preclinical degenerative mitral valve disease.
Larouche-Lebel É1, Loughran KA1, Oyama MA1,2.
https://onlinelibrary.wiley.com/doi/full/10.1111/jvim.15461
These authors found that three dimensional indices such as MV regurgitant fraction are relatively easy to measure and are more sensitive indicators of severity of MVD in pre-CHF dogs. This reinforces the conclusions to be drawn from another recent article:
J Vet Intern Med. 2019 Jan 9. doi: 10.1111/jvim.15408. [Epub ahead of print]
Comparison between real-time 3-dimensional and 2-dimensional biplane echocardiographic assessment of left atrial volumes in dogs with myxomatous mitral valve disease.
Tidholm A1,2, Bodegård-Westling A1, Höglund K3, Häggström J2, Ljungvall I2.
https://onlinelibrary.wiley.com/doi/epdf/10.1111/jvim.15408
…who found poor correlation between 2D measures and volume derived from 3D echo.
I think anyone who does a fair few echocardiograms on a regular basis will know that the left atrium is a complex 3D structure and that measuring 2D indices such as LA:Ao involves a degree of judgement as to optimal alignment: resulting in appreciable inter- and intra-observer variation. We have real reservations about the push (at least in the UK) to persuade general practitioners that they can assess the need of a murmur-bearing patient for pimobendan based on LA:Ao measurement.
This is all quite significant. The EPIC study is the only evidential basis for a recommendation that dogs with pre-CHF MVD are likely to benefit from pimobendan. The raw data has not been made available and this leaves us unable to slice and dice it in any other way from that in which it was published if we don’t like the assumptions behind the analysis provided.
And pimobendan isn’t necessarily an entirely benign intervention if prescribed unnecessarily. There is evidence that it can exacerbate mitral regurgitation and induce valve lesions.
Cardiovasc Toxicol. 2005;5(1):43-51.
Increased mitral valve regurgitation and myocardial hypertrophy in two dogs with long-term pimobendan therapy.
Tissier R1, Chetboul V, Moraillon R, Nicolle A, Carlos C, Enriquez B, Pouchelon JL.
https://www.ncbi.nlm.nih.gov/pubmed/?term=tissier+pimobendan+dogs
Increased mitral valve regurgitation and myocardial hypertrophy in two dogs with long-term pimobendan therapy.
Tissier R, Chetboul V, Moraillon R, Nicolle A, Carlos C, Enriquez B, Pouchelon JL.
Cardiovasc Toxicol. 2005;5(1):43-51.
https://www.ncbi.nlm.nih.gov/pubmed/15738584
It seems likely that we will move towards deciding when to start pimobendan on the basis of something like regurgitant fraction >50%…..but ideally we’d like another study please!
