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Melanie Cole (Host): Degenerative mitral valve disease is the most common heart disease affecting dogs and the prevalence of the disease increases with increasing age. So that nearly all older and small breed dogs are affected to some degree. Ongoing research at UF aims to enhance treatments aimed at improving the lives of dogs living with heart disease. Welcome to UF Vet Med Voice with the University of Florida College of Veterinary Medicine. I'm Melanie Cole.

Joining me today is Dr. Darcy Adin. She's a clinical professor of cardiology in the department of large animal clinical sciences at the University of Florida College of Veterinary Medicine. Dr. Adin, it's a pleasure to have you join us today to discuss improving the lives of dogs with heart disease or mitral valve disease. Can you tell us a little bit about what we're talking about here today? Why does early detection of heart disease and potential therapeutic targets in early stages of disease remain extremely challenging? Tell us a little bit about what's been happening and how this is Evolving?

Dr Darcy Adin: Thank you Melanie. And thanks for having me on this, mitro valve disease really affects millions of dogs in our country. It is the most common heart disease that we see as veterinary cardiologists. And so it is challenging in the fact that it affects many different dogs. and as dogs get to be geriatric dogs, it's very likely that they have some degree of the heart disease, but not every dog that has Mitra valve disease will suffer clinical signs or symptoms because of the disease.

And so our challenge is to find that proportion of the population that is affected and will go on to develop symptomatic disease and try to intervene with medications to slow that progression of disease. And then once they become symptomatic, our goal is to make them feel as good as they possibly can with the heart disease and live the best quality of life that they can during that time when they're symptomatic, which is typically going to be congestive heart failure.

Melanie Cole (Host): So has management of heart disease in dogs, largely been focused. Dr. Adin on supportive. And symptomatic therapy with few therapies available to really treat or manage that heart or valve disease that has been shown to approve outcomes. Is this something that is evolving in its own way that way, as far as supportive and symptomatic therapy, what's going on in the field?

Dr Darcy Adin: Well, you're absolutely right. the vast majority of the treatments to date have really focused on medical therapy, which doesn't fix the underlying problem of the valve being degenerate or showing age related changes. And once that valve becomes thickened and shows degenerative changes, then it meet properly or COAP properly. And blood can go backward when it should go forward. That's called regurgitation.

And that can lead to enlargement and elevation of pressures, within the heart that then can lead to signs of congestive heart failure, typically difficulty breathing and coughing. And so, the vast majority of Medications that we have available to us are intended to try to either delay the progression of the disease, or once the disease has become symptomatic to relieve the clinical signs of the disease.

But the disease usually. Continues to progress, because we're not fixing the primary problem. Now we are living in a day and age. That's exciting to us because in addition to some new medical therapies that are available to us, we also have various groups working on ways to fix the primary problem. So there are a few interventional approaches that are under investigation and gaining momentum now to try to mechanically, bring the valve closer together and reduce the amount of leak in the valve.

And there are also a few centers throughout the world that have some very skilled surgeons that are perfecting the technique of open heart surgery and bypass to try to actually repair and fix the valve itself. Those novel interventional and surgical approaches to try to fix what is the primary problem are not widespread. And they tend to be quite expensive. And so the vast majority of dogs that have the disease across the world are being treated with medications at least for the time being. But I think there's hope in the future that that may become more accessible to have techniques that can actually fix the problem.

Melanie Cole (Host): What about things like Taver? Has that been looked at in dogs? It's minimally invasive valve replacement. Are we looking at that?

Dr Darcy Adin: Valve replacements have been looked at in the past, years, a while ago, and they have not been successful. Probably multifactorial, but one of the problems is that dogs tend to form clots and from both artificial valves a little bit seemingly more frequently than people. And so the current surgical approach that's being undertaken by the very few centers across the world who have been successful with it is valve repair. And that does have a very high success rate. But again, it's not available to us right now in the United States and it is not widely accessible, unfortunately.

Melanie Cole (Host): This is so interesting. And it's really something that I would assume affects many and is important to many dog owners and veterinarians alike. What about prevention, Dr. Adin, as in humans, is there any correlation with lifestyle factors, activity, diet that could help stave off or prevent heart disease or valve issues in dogs?

Dr Darcy Adin: Yeah, that's a really great comment, Melanie. Because the problem with mitral valve disease anyway, this particular disease, is a mechanical one with the valve becoming thickened, and not collecting properly. That does not appear to be significantly influenced by lifestyle or diet. And while groups have not identified an exact genetic mutation associated with the disease, there are, quite a few studies that suggest that it does have a genetic basis and it might be polygenetic, there might be several genes that influence the expression of the disease.

And so, with the genetic basis there it's, unlikely that, a significant, environmental effect will be the cause. Although certainly we know that diet and environment and things like that can influence the expression of genetically based diseases. And so right now the focus is, on trying to find the genetic mutations. And there are certainly groups that are working on that and then try to breed away from dogs that are positive for that, or have the expression of the disease. And so one example would be, even though we don't have a genetic mutation identified.

There are programs, especially in some of the European countries that have tried to selectively breed away from dogs that are severely affected at a young age to try to take those severely affected dogs out of a gene pool. And in some countries that has shown success in reducing the, percentage of dogs within certain breeds that are affected. But the reality for most veterinarians in practice is that they are gonna see these affected dogs, not at the preventative stage, but at the stage where they start to have disease.

And so that is a time where we are looking to say, okay, is there a medication or some medications that we can use to try to intervene at an early stage that at least could delay the progression of disease. And to this point, we. One medication available that has been very conclusively shown to delay the progression of disease in dogs that are identified at an early stage. And there are other medications that have been looked at with varying results, but the one that we know will delay the progression of the disease, in an earlier stage is Pimabendon. And that medication, will delay the onset of clinical signs by about 14 or 15 months, which is a significant amount of time for most owners.

Melanie Cole (Host): So, this is so interesting. Now, before we get ready to wrap up Dr. Adin. Any research that you're doing at the University of Florida College of Veterinary Medicine that you would think other providers would want to know about. Can you tell us about any clinical studies in the cardiology service that are actively enrolling dogs with congestive heart failure to investigate novel therapies and refined current ones? How can referring vets get in on any of these?

Dr Darcy Adin: Yeah, that's a great question, too. And to this point, We've only talked about, the pre congestive heart failure dog, but once dogs go into congestive heart failure, then we're typically treating them with diuretics. We're also using Pima Bendin inhibitors of the renin angiotensin aldosterone system to try to blunt those effects of the failing heart essentially. We are very committed to improving the lives of dogs with congestive heart failure here at the University of Florida College of Veterinary Medicine and some of the studies that we've done in the past and are still looking at include trying to look at what influences a dog's response to those medications.

And we do know that there are genetic variants that can affect the, expression of the Renin angiotensin aldosterone system. And so we are looking at that, we're looking at ways to intervene with that nutritionally, with nutritional supplements, like tourine. And then we have an active, clinical trial going on right now, which is looking at dogs that have low blood chloride concentrations and randomizing dogs to a medication or placebo that can help to increase those chloride concentrations. And the reason that we're looking at this is that hypochloremia has been shown in several studies.

One of which was done here at the university of Florida has been shown to be a poor prognostic indicator for dogs that have congestive heart failure. So if they come into the hospital and their blood chloride, level is low, they do worsen the outcome. And that's probably because having the low blood chloride, which historically has been ignored, has the ability to ramp up the renin angiotensin system, which is male adaptive and causes more problems. And so if we just ignore that and we let it go, those dogs don't do as well. But one of the problems is that there are not many drugs out there that can raise that up.

And in fact, the drugs we use for treating congestive heart failure typically cause wasting of that through the kidneys. And so we have funding right now with a clinical trial to look at a medication that can be directed at improving those blood chloride levels. And that drug is called acetazolamide. It's a diuretic that we are adding on standard of care medications. And the purpose of our study is to determine if we intervene with this medication and can raise the blood chloride levels up into the normal range.

Do those dogs then go on to do well? So the first part of our study is first determining if that drug is effective in the context of a heart failure patient, getting the other standard of care medications. And then we would hope to go on and look at outcomes later.

Melanie Cole (Host): Well then Dr. Adin, will you please wrap this up? What you would like the key takeaways to be for other providers when we're talking about improving the lives of dogs with heart disease, mitral valve disease, and that are affected by these diseases and even in the pre disease state, wrap it all up for us?

Dr Darcy Adin: Well, I'm very passionate about this disease because it is a disease that is very common and it affects millions of dogs. And these are dogs that we love that are part of our family. And even though this is a disease that ends a small percentage of dogs, about 25% of dogs that are affected. They can go on to develop heart failure. We are committed to identifying those dogs, trying to delay the progression of the disease. And if they are dogs that will go on to develop signs of congestive heart failure. We want to do all that we can to make them as comfortable as possible. Not just for our patient, but the results of the studies that are coming out of the University of Florida will hopefully positively impact dogs all over the world.

Melanie Cole (Host): Beautifully said, thank you so much, Dr. Adin for joining us today. What a great topic that you were discussing both for pet owners, as you said, they are members of our family and for other veterinarians, keep doing that research and join us again. As you have more to update and for more information about improving the lives of dogs with heart disease or mitral valve disease, please visit vetmed.ufl.edu/ufachievers. Or to listen to more podcasts from the experts at the University of Florida College of Veterinary Medicine, please visit vetmed.ufl.edu. That concludes today's episode of UF Vet Med Voice brought to you by the University of Florida College of Veterinary Medicine, advancing animal, human, and environmental health. I'm Melanie Cole.