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Pulmonary hypertension in dogs with Myxomatous Mitral Valve Disease | VETgirl Veterinary CE Podcasts

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In today’s VETgirl online veterinary CE podcast, we review the significance of pulmonary hypertension in dogs with myxomatous mitral valve disease (or what we’ll call MMVD from now on). Pulmonary hypertension (PH) is thought to commonly occur in dogs with MMVD due to passive elevations in pulmonary venous and capillary pressures; this can progress to pulmonary arterial vasoconstriction and remodeling of pulmonary vasculature (with the latter considered an irreversible stage).

How do we diagnose pulmonary hypertension? Cardiac catheterization is the definitive means but echocardiography provides the best noninvasive method, and is the most common method to detect pulmonary hypertension in animals. So what are you looking for (well, your veterinary cardiologist looking for) to determine if your patient has pulmonary hypertension or not? Diagnosis of pulmonary hypertension via echocardiography occurs via measurement of peak tricuspid regurgitation velocity – specifically, a peak tricuspid regurgitation (TR) velocity of > 3 m/s. (This is in the context of the entire echocardiogram/clinical picture of the patient). This velocity measurement corresponds to a pressure gradient across the tricuspid valve (thus a right ventricular-to-right atrial pressure gradient) via the equation pressure gradient = 4v2, where v = velocity. During cardiac systole, the right ventricle and pulmonary artery pressures are virtually equilibrated, thus we can also infer this measured velocity to provide an estimated pulmonary artery-to-right atrial pressure gradient. Since right atrial pressure remains relatively low or close to zero, even in states of significant right-sided disease, we can therefore further infer this pressure gradient to be a rough estimate of systolic pulmonary artery pressure itself. Normal systolic pulmonary artery pressure is approximately 25 mm Hg. Accounting for sources of error/inaccuracy, the generally accepted pressure gradient for detection of pulmonary hypertension is a peak tricuspid regurgitation pressure gradient > 36 mm Hg, or a peak TR velocity > 3 m/s.

At any rate, back to why we care about pulmonary hypertension.

Due to the prevalence of pulmonary hypertension in dogs with MMVD, Borgarelli et al. wanted to study and evaluate the prognostic importance of pulmonary hypertension in MMVD. In their paper “Prevalence and Prognostic Importance of Pulmonary Hypertension in Dogs with Myxomatous Mitral Valve Disease” that was published in March of 2015 in the Journal of Veterinary Internal Medicine, they retrospectively investigated the effects of pulmonary hypertension on survival time in dogs with MMVD in a multi-institutional study.

In this study, they looked at a total of 212 dogs with Stage B2 or C MMVD, based on ACVIM staging classifications found here. Stage B1 (in other words, those with a normal heart size) and State D MMVD (in other words, those with refractory CHF) were excluded. Patients with concurrent tracheal collapse or history of heartworm disease also excluded. Of the 212 dogs included, there was an equal distribution between stage B2 and C MMVD, with no difference in age or weight at baseline. The study end-point was defined as death (which included all causes). Almost 50% of the dogs died during the “observation period” in this study.

Overall, 39% (83/212) of dogs with both Stage B2 and C MMVD were diagnosed with pulmonary hypertension, with it being more common in dogs with stage C vs. B2 MMVD. The median survival time for all 212 dogs was 567 days. When looking at the median survival time based on ACVIM Staging, Stage B2 dogs averaged 784 days, while Stage C dogs averaged 491 days. In those dogs without pulmonary hypertension, overall, the dogs had a median survival time of 758 days. Those dogs with pulmonary hypertension in either Stage had a medial survival time of only 456 days. What they found on echocardiogram that was a predictor of a worse outcome: If the peak tricuspid regurgitant pressure gradient is > 55 mm Hg or the left atrial to aortic root ratio is > 1.7.

So, what do we take from this VETgirl podcast?

Pulmonary hypertension occurs relatively frequently (39%) in dogs with stages B2 and C MMVD, and more frequently in stage C dogs overall according to this study. This finding is consistent with the known pathophysiology of pulmonary hypertension in left-sided heart disease in humans and animals. The presence of pulmonary hypertension in stage B2 and C MMVD dogs is associated with a worse outcome, and specifically the presence of pulmonary hypertension with a peak tricuspid regurgitation pressure gradient > 55 mm Hg as assessed echocardiographically was a significant predictor of worse outcome in these patients.

It’s important to note that absolute pulmonary hypertension to any degree (TRPG > 36 mm Hg) was NOT a predictor of worse outcome in multivariate analysis. This suggests that milder severities of pulmonary hypertension (presumed predominantly passive) secondary to MMVD may not impact survival in the way that more advanced, and presumed irreversible, pulmonary hypertension does. Various terms exist to describe this latter category in humans including “out-of-proportion” and “reactive” PH. Given that most dogs with MMVD are of small breed variety and the high prevalence of chronic lower respiratory disease in these breeds, it is possible that dogs with more severe degrees of pulmonary hypertension have a concurrent contribution from respiratory disease, as well. This study attempted to exclude dogs with overt primary respiratory disease, however.

VETgirl’s take on this study?

Despite its retrospective nature, this study provides useful data on pulmonary hypertension in MMVD and is put forth by a highly reputable/distinguished international group of veterinary cardiologists. As the authors state in the manuscript, echocardiographic measurement of peak tricuspid regurgitation velocity can be fraught with error and inaccuracy, and interpretation of any obtained value must be taken in the context of many other factors, which emphasizes the importance of having specialists such as cardiologists perform such evaluations. The fact that dogs with advancing MMVD are more likely to have pulmonary hypertension is not a surprise, but the first statistical evidence to suggest that the degree of pulmonary hypertension present matters from a prognostic standpoint is important and may have ramifications for therapy with regards to selection of patients with MMVD and concurrent pulmonary hypertension for treatment with phosphodiesterase type 5 inhibitors (ie sildenafil, tadalafil, etc). In other words, pass the Viagra and treat that underlying respiratory disease earlier than later!

References:
1. Borgarelli M, Abbott J, Braz-Ruivo et al. Prevalence and Prognostic Importance of Pulmonary Hypertension in Dogs with Myxomatous Mitral Valve Disease. J Vet Intern Med 2015;29:569-574.

Abbreviations:

PH: Pulmonary hypertension

MMVD: Myxomatous mitral valve disease

ACVIM: American College of Veterinary Internal Medicine

CHF: Congestive heart failure

TRPG: Peak tricuspid regurgitation pressure gradient

PG: Pressure gradient

TR: Tricuspid regurgitation

LA/Ao: Left atrial to aortic root ratio

 

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