The BSM Partners Research Team has dug deep into existing research on canine dilated cardiomyopathy (DCM), so you don’t have to. Join us as we uncover the rigorous processes behind peer-reviewed research, discuss the importance of identifying “fatal flaws,” and highlight how we can use literature reviews to pave the way for future research—and to debunk understudied or unsubstantiated preconceptions about pet health and nutrition.

Helpful Links

Board-Certified DCM Literature Review (Full Text): https://academic.oup.com/jas/article/98/6/skaa155/5857674?login=true

DCM Incidence Study (Full Text): https://www.frontiersin.org/articles/10.3389/fanim.2022.846227/full

DCM Incidence Episode — A Mountain, or a Molehill? What Science Really Says About the Incidence of DCM 

Study Design — Think Twice: Even Bad Science Can Get Published!

Show Notes

00:00 – Welcome

03:12 – Introducing Dr. Anna Kate Shoveller and The Importance of Literature Reviews

06:30 – “Fatal Flaws” in Peer-Review

09:39 – What Inspired BSM Partners to Study DCM?

12:49 – What Exactly Is DCM in Dogs?

16:18 – Genetics as a Key Cause of DCM

19:11 – How Is DCM Diagnosed?

22:27 – Potential Treatment Options for Dogs Diagnosed with DCM

26:06 – Getting to the Root Cause

26:54 – Nutritional Interventions to Combat DCM

28:54 – How Nutritional Deficiencies Could Harm the Heart

30:38 – Writing a Board-Invited Literature Review on Canine DCM

33:25 – Identifying Gaps in the Research

36:44 – Limitations that Informed the FDA’s Announcements

42:15 – Darned If You Do, Darned If You Don’t

46:52 – Conclusion and Farewell

During this pivotal moment in the pet care sector, BSM Partners took the initiative to gather the facts and get to the truth. If you've been following along, we've taken you on a detailed behind the scenes account on the science of nutrition and DCM and dogs, including extensive retrospective and prospective research aimed at helping answer pet lovers' questions and concerns.

The research team at BSM Partners has published quite a bit of research, but its first publication was a board-invited review of all the research that has been conducted on DCM in dogs. This included topics like: What do we already know about this complicated heart condition in dogs? What doesn't the research tell us?

This type of study is called a literature review, and BSM Partners literature review on DCM remains one of the most read publications in the Journal of Animal Science today. In today's episode, the research team will explain what their extensive research found, and the key takeaways that pet owners and industry members at large should know.

I'm thrilled to welcome an outside expert and past guest to share a bit about literature reviews and what it takes to publish in a peer reviewed journal. This guest, Dr. Anna Kate Shoveller, is a PhD animal nutritionist, researcher, and professor at the University of Guelph. Dr. Shoveller is also an editor for several peer-reviewed journals.

We also have four members of the BSM Research team on the call today to talk about their extensive literature review on DCM and dogs. This includes Dr. Bradley Quest, Principal of Veterinary Services at BSM Partners, board-certified veterinary nutritionist, Dr. Renee Streeter, and two PhDs and board-certified animal nutritionists, Dr. Stephanie Clark and Dr. Sydney McCauley.

Get ready to be informed, enlightened, and maybe even a bit surprised as we unlock the mysteries of DCM. Welcome to Barking Mad, a podcast by BSM Partners. I'm your host, Jordan Tyler.

Dr. Shoveller, first of all, thank you so much for joining us today. I'm very much looking forward to your perspective on literature reviews and the review process that goes behind getting a paper published in a peer-reviewed journal.

Now, you've been focused on research for quite a bit of your career, and you've not only reviewed other people's literature reviews, but you've also written them. So, would you mind telling our listeners a bit about why literature reviews are so important for research?

Anna Kate Shoveller: Absolutely. I always say that the importance here is being able to see the forest for the trees. So, you cannot—you can't base any single study on one other study that you read. You need to explore the literature, you need to find the gaps, and you need to place the appropriate questions to answer those gaps. And there's never just one study that will do that as well. So, that is why literature reviews are important prior to starting any study that you want.

Jordan Tyler: Oh, absolutely. And I would imagine there's a ton of work that goes into all of this. Do you mind elaborating a little on what's involved?

Anna Kate Shoveller: I think you know me well enough to know that I prefer to bring in all the experts in the area, and I really like to bring in people when I think they might have a different opinion or a different perspective as well, because diversity of thought improves everything that we do. So, that's building your team, your literature review team.

In terms of process, you kind of start with, so what's the bones of what we're talking about here? And you kind of start with not so much a table of contents necessarily, but an idea about the areas that you're thinking about discussing. And then there's just an insane amount of iterations to really flesh out what our current understanding of the topic is. And we bring in experts who continually just point out, “You missed this, you misinterpreted that, you missed this.” You know, “What the connector is over here was this.” And so, it's kind of got a duplicitous role when we make trainees do these, because it really helps them also explore how deeply they need to understand things and where they could possibly see connections.

Some individuals are great at seeing scientific connections and can piece together simple basic studies that are maybe exploring one or two outcomes, all the way up to epidemiological studies that will put a lot of variables into one basket, as an example. And so, it really gives the trainee an opportunity to flex their ability to understand all kinds of different science.

Jordan Tyler: Like a little melting pot of scientists. I can totally see how bringing diversity of thought and opinion to the table can really benefit these review processes. So, now that we know a little bit more about what goes into a literature review, can you speak to the review process a little bit? I imagine it's similarly robust.

Anna Kate Shoveller: The responsibility as a reviewer, and I think that most people, even people with PhDs and postdocs sometimes don't really understand what that responsibility is. You are not a gatekeeper as either a reviewer or an editor. You are there to handle a paper, to make sure that you bring the best and most innovative science forward that is fully and transparently describing the science so you could potentially repeat it because the killer issues are if you try to repeat someone's study, and you get different results.

This is where we have a really hard time coming to a consensus. And then we throw around other possible outlets of why you might get different results. And of course, epidemiological studies, and it's sometimes much harder to reproduce results because you're pooling so many variables but not measuring any one of them individually, so they might have more of an effect in one study than another, as an example.

Ultimately, the really hard reviewers are looking for all of that and are doing it in a way to elevate science. When you are reviewing, I think if reviewers would remember that their job is to decide whether there are killer issues, and those would need to be very clearly defined. So, in science, we would call that a fatal flaw.

That usually comes in the form of a design flaw. So, while it's not just the gross design of the project, if they designed their test diets wrong, that's rejectable, to make sure that they're focusing their diet design based on interrogating the objectives and hypotheses of the study is also a potential killer issue.

Everything after that. Should be questioned and discussed and potentially changed, but I think that's the other thing that's really, really important for authors and reviewers to think about is you are now getting probably one of the experts in the area reviewing your work. And they should, if they're really good reviewers and there's no fatal flaws in your study, they should make your paper better.

And that's the role of the reviewer and that's the role of the author too. Also, authors listen to those questions to think about whether it requires a change in the manuscript, but whether it just needs a rebuttal to the review, and that's why we do rebuttals to the reviewer.

Jordan Tyler: All really, really, great points, so thank you for that. I'm going to turn things now to the BSM Research team. Now, we've established that really any peer reviewed paper takes a ton of work, and this literature review from BSM Partners was very long, very detailed. I'm getting a little ahead of myself here, though, because what I really want to ask Dr. Quest is this. From your perspective, what do you think urged BSM Partners to decide to step in in the first place and extensively review all this research about DCM and dogs?

Bradley Quest: I think, a lot of it is us, as working with inside the pet food industry where we, we formulate, we do nutrition, we do product testing, we do claim substantiation, we do a lot of things for a lot of different brands and a lot of different pet diets.

I think a lot of it is for us as industry experts and nutritionists and product formulators to understand what is being said, why is it being said and what's being published or communicated? What is it as exactly based on? Because it's our responsibility to both the pets and the consumers to be able to work and help our clients produce the most nutritionally sound diets that we can. So, a lot of it is around helping to educate us as industry professionals why things are being said.

Jordan Tyler: Yeah. That's so true. And as Dr. Shoveller was saying earlier, most research should start with a detailed look at all of the current literature that's been published on a particular topic just so that you can understand challenges and limitations and gaps and potentially misinformation.

Stephanie Clark: To what Dr. Shoveller had said about really diving into the details and understanding the topic, this is what we wanted to do with DCM. There was a communication about DCM and potential connections of diet and the cause of it. It caused this great shift, not only in industry, but pet parents' confidence and what they were feeding.

But before we started any research, we needed to do a deep dive into all the potential factors of DCM. DCM is a multifactorial disease. This means that many causes can lead to this disease. both internal and external factors, such as infections or hypothyroidism, nutritional causes, and even genetics.

So, taking the time before beginning to design a research project, we needed to establish just the basics. For me personally, I came from the veterinary world and into industry. I didn't fully understand all the history and causes of DCM. So, when I actually came into industry, this was my first project, and I definitely learned a lot, which I believe really helped us design a highly controlled and thorough prospective study.

Jordan Tyler: That's a great point as well. Now, coming back to what you said about DCM being multifactorial, I was wondering, Dr. Quest, if you could give a high-level overview about what DCM actually is in dogs.

Bradley Quest: Yeah, absolutely. So, there's a lot of different conditions that kind of get lumped into the DCM category. We like to use the term, and we use this because we've consulted and worked with so many veterinary cardiologists here the past few years, but we like to use this word, DCM phenotype. And phenotype, it just simply means “looks like” so, it looks like a large heart.

We know that according to the veterinary cardiologist, the only definitive way to diagnose DCM is to have an echocardiogram and in a lot of cases, multiple echocardiograms taken at different time points and then have those echocardiograms read and interpreted by a board-certified veterinary cardiologist. Dr. Clark hit on it; at least in our current knowledge base, genetics is probably one that comes to mind. A lot of breeds we know are genetically predisposed to developing. It doesn't mean like all dogs in a certain breed will develop DCM, but we know it can play a really big part.

Dr. Clark and Dr. Shoveller talked a lot about nutrition and obviously, nutrition is huge. According to past research, there are certain deficiencies and certain micronutrients, amino acids, things like that, that in some cases, can definitely lead to DCM or a DCM phenotype.

And then another thing Dr. Clark hit on is infectious causes. And there's at least enough preliminary research to show that conditions such as myocarditis—I know when, when we first started kind of looking at this and talking to more and more people and trying to educate ourselves more and more on just DCM, in general, being in touch with some of these cardiologists who have actually done a myocardial biopsies or were able to do postmortem analyses and discover that some of these dogs that had DCM that were kind of otherwise unexplained. And I'm using air quotes. They actually link back to different disease processes, like viral infections and such.

The word multifactorial, I know we've used it, a lot of people use it, it gets thrown around, but I really think it really, really fits kind of sometimes the perfect storm type of scenario. You might have a dog that may or may not be genetically predisposed. Maybe he had a viral infection. Maybe he's a breed that has a different amino acid requirement and we don't know everything about nutrition, we know a lot, but it's always evolving. And I think a lot of these things together in some individuals, you can see conditions like a DCM phenotype, and we may not be able to explain it all right now.

Hopefully, someday we will, but what we try to do is do controlled research like Dr. Clark spoke about to try to flush out if we can identify causes of conditions like that.

Jordan Tyler: Totally. Yeah, I remember back to the episode we did with Dr. Justin Thomason, a veterinary cardiologist, that was looking at DCM incidence, or the incidence rate of DCM cases, and he mentioned one of the most common causes of DCM is an inherited genetic mutation. So basically, certain breeds are predisposed to developing DCM while others are not. Dr. Streeter, what might breeding have to do with this factor of DCM?

Renee Streeter: There may be things we can do to help prevent it. I don't know if we'll ever completely prevent it, right? Especially if it is genetic, but good breeding practices. Like if you know that your dogs have the gene for DCM, not breeding them would be the most responsible thing to do. So, there are things that we can do to alleviate or mitigate or reduce the incidence, perhaps through breeding practices.

Jordan Tyler: To further build on what Dr. Streeter mentioning here, when it comes to comparing breeding practices in the European Union to those in the United States, Europe is more comprehensive. The EU has stricter regulations on animal breeding and selling. In Europe, breeders are legally required to have proven competency, and they must follow specific practices for welfare, as well as biosecurity.

Also, European breeders are restricted on breeding that could be harmful to the pet, such as inbreeding or breeding for extreme physical traits. Think of all those smush-faced dogs out there that can have trouble breathing. This is a no-no in Europe. Additionally, European breeders are required to conduct genetic screening tests before breeding a dog, and this is to identify “carriers,” or dogs who aren’t affected by a disease but carry the mutated gene for it and could therefore pass it on to their pups.

Breeders and sellers in the European Union must also adhere to some level of traceability to keep track of where the animals are going, and where they came from, and this includes providing genetic screening results to prospective new owners. So, lots of stopgaps here to try to reduce genetic predisposition to certain diseases in dogs.

Renee Streeter: But like we just keep talking about, this is not just genes. Maybe it's genes and the other things they all are working together to cause the disease process.

Jordan Tyler: That's really, really fascinating. Thank you for sharing that Dr. Streeter. This to me really underscores the importance. Now, Dr. Quest, you've mentioned the phenotype of DCM, as well as some diagnostic techniques used to actually diagnose DCM. Could you please describe a little more about how veterinarians diagnose this condition?

Bradley Quest: Yeah, I think, I think Dr. Shoveller had mentioned it earlier in the review process, but the way we approached our research into this topic is to try to gather as many experts that we could and that includes a lot of veterinary cardiologists to consult with and to help educate us and to help us as we design our research.

Some of the tools, and again, this comes from the veterinary cardiology community, like the general practicing veterinarians can use, obviously you can take radiographs or simple x-rays to kind of start looking at, “Hey, does this dog's heart actually look bigger on an x-ray than it should,” and then that can help you maybe rule out some other causes of what's ailing the pet.

There are enzymes and biomarkers that you can actually draw blood on a dog and send to a lab. In fact, one of the tests is actually being developed to do in clinic to look at cardiac biomarkers and that can be another screening test that can help identify whether you're dealing with a problem of the actual cardiac muscle or the muscle of the heart itself. Now, it doesn't definitively diagnose DCM, but it helps kind of narrow things down. ECG, that's another tool that can help. But again, it's not a tool that can definitively diagnose DCM, but it can kind of narrow these things down.

When it really gets down to it, you really need a board-certified veterinary cardiologist. You really need an echocardiogram to be interpreted by somebody who's qualified to do that. And then in some cases it can take multiple, because every patient's going to be different. They're all going to be different in that disease process. It's not always black and white. And then there are other conditions that can look like a dilated heart, and it may actually not be kind of classic DCM, but it could be other things.

There are conditions; there are valve disease conditions that can easily look like dilated cardiomyopathy on an x-ray and even sometimes on echoes. And the reason I say this is just because we've talked to enough cardiologists and we get enough, we lean on them for their expertise and things that they've seen to help us in our research and in our study designs and interpretations of those.

Jordan Tyler: Yeah, it's good to point that out too. Just like in human medicine, veterinary medicine is full of different types of specialists. And there's a reason these people are experts in their particular fields. So, it's always great to have a diverse array of topic experts handy when you're trying to understand a situation as complex as DCM.

So, we've talked about diagnostics. Maybe let's shift to treatments. I'm sure pet owners out there are curious. Dr. Clark, what are some potential options for a dog diagnosed with DCM?

Stephanie Clark: Absolutely. I can speak on this and then Dr. Quest and Dr. Streeter, please jump in as the DVMs on this podcast.

And it really is, there are so many options such as supplementing with taurine. There are some heart healthy diets out there that are a little bit more controlled in sodium or other nutrients that can add a little bit more workload to the heart. And then of course, FDA-approved medication out there as well. I'm sure each veterinary cardiologist is a little different in what they're going to recommend.

And I'm sure it's going to differ between dog to dog and dog to cat, as they're all individualized. Between supplements, diet change, and medication, you've got a little bit of selection on how you want to treat this and how much you want to treat it.

From personal experience, my beagle, when she was diagnosed last year, was on some diuretics. She was on Pimobendan. We changed her diet, but we did not supplement her with taurine at that time. So that was just one avenue that we did and that was just a personal experience for my dog. She made it 18 months with a diet change and medication, and I'll take those 18 months. I think it was great, and she was still a very happy beagle for all 18 months.

Renee Streeter: Did your dog have DCM or congestive heart failure?

Stephanie Clark: It was mitral valve disease, and then she got diagnosed with DCM as it progressed. But initially it was just mitral valve. And I guess technically before all this, she just had a heart murmur that we were watching. Like most heart diseases, it kind of progresses and just gets worse and worse and worse until finally she was just in heart failure towards the end of it.

Renee Streeter: You know, you do have this personal connection and personal experience with it that is not fun to go through, but I'm sure now you feel it both academically and personally. So, I'm sorry. Treatment is going to depend on the underlying cause, like in Dr. Clark's case, where mitral valve disease may have preempted some of the cardiac disease initially a lot of people will treat with something like Pimobendan than if there is congestive heart failure with a diuretic like furosemide, and that's pretty common.

We often test for amino acid deficiencies that could contribute like taurine and carnitine, and more to come on those tests and the validity of them, but we do test and see if supplementation may be warranted to help with some of that. And in particular breeds, we do know that they can help.

And then like Dr. Clark was saying, a cardiac diet in terms of nutrients, we would focus on, it's like omega-3 fatty acids. Sometimes we add B vitamins if they are on diuretics in order to assist with replenishing those losses and then low sodium as well. So as not to affect the heart, the blood pressure as much. So, there's a lot of things that we can do to treat or mitigate the disease.

Jordan Tyler: Yeah. And treatment would also probably depend on the primary cause of the dilated cardiomyopathy, right? Because DCM as a condition is really just describing the enlarged heart and thinned muscles. But how can we tell the reason why a dog developed the condition in the first place?

Renee Streeter: Yeah, and use things like cardiac muscle biopsies to look at the muscle fibers and they can give us clues as to the initial origin of the dilation. But that is a very tough test to undergo, right? Definitely only through a cardiologist and then even then only some will do that procedure and then the rest is genetic testing to see if that's a component and then endocrine testing to see if that's a component treat any underlying endocrine issues.

So, it's a full workup Right? And then treating the dog as a whole, as well as treating the heart.

Jordan Tyler: Definitely a good point. Now you started to talk about what we can do nutritionally to support a dog with DCM, which is interesting because the initial question was about whether a certain type of diet caused or contributed to the development of DCM.

That's the whole reason this literature review project was started because people were worried about the potential link between the disease and the diet. Now, if you've been following along in our DCM series, you'll know it's much, much more complicated than just diet alone. Coming back to the term multifactorial, as it turns out, there are a lot of things that we can do nutritionally for dogs that develop DCM, regardless of the cause, things that boost heart health.

So, Dr. Streeter, would you mind sharing how nutrients can play a role in heart health and maybe which nutrients are key for this?

Renee Streeter: So, having a balanced diet I think is the first and foremost, and I will take this opportunity to tell stories, right? Like about some patients that come to me and their dog has a heart condition. And instead of ensuring a complete-and-balanced diet, they take the diet that they're on and add grains to it. And so that's going to further dilute out on an energy basis, the vitamins and minerals and amino acids.

So, it's not like adding something to it, like in that manner it is going to mitigate the issue. You really have to ensure first and foremost that the diet has all the required nutrients, amino acids, vitamins and minerals, fatty acids, all those things are going to play into a healthy heart and a healthy animal in general.

Jordan Tyler: Oh, that's a really great point. What about vitamins and minerals like B1, thiamine, copper, and potassium. There's just a ton to consider here. Dr. McCauley, would you mind explaining how some of these potential deficiencies in a diet could contribute to damage to the actual heart muscle of a dog?

Sydney McCauley: So, a lot of these vitamins, minerals, and amino acids, for instance, some of our B vitamins very much intertwined with methionine, cysteine, and taurine. They all kind of interlock in that sulfur amino acid pathway. And so, it's where these deficiencies are actually happening. Is it one causing another is another and creating a bigger problem to shut down another system and creating a deficiency? Like, what kind of feedback mechanism are we having?

And I think really all these together, it goes back to what Dr. Streeter was ultimately saying of complete-and-balanced. Sometimes more is not the answer. Vitamins, minerals, everything, we don't need to just supplement, supplement, supplement, right? Because what we could be doing is creating, again, another problem, which is an interaction issue of unbalancing any of those ratios of minerals, amino acids, and creating issues in that aspect.

Jordan Tyler: Absolutely. It's like a puzzle of its own. Each of these nutrients is playing off each other, which is playing off another, and they're all connected and interacting to carry out multiple roles in a pet's body. That's just super fascinating and really puts into perspective just how critical it is that diets are formulated and balanced appropriately, because one tiny mistake could throw the whole matrix out of whack.

So, back to the topic at hand, you're sitting down to write this literature review and probably your desk is just overflowing with supporting materials, right? Plus, this is a super-hot topic, and everybody wants answers. No pressure. But so, you've taken on this huge project, you've found all these qualified experts to collaborate on writing this paper. Dr. McCauley, I'm curious, what was the experience of writing this literature review like for you?

Sydney McCauley: I can speak on my portion of writing this paper. It was just like any other grad school requirement for writing it. It was a lot of hair pulling, a lot of grays, and a lot of us going, “Did we really…” How do we make it so it's adding to what others have out there, but also filling in gap people focus their lit reviews on one thing? Can we focus differently, like what can we add to the knowledge that's out there?

Jordan Tyler: Yeah, not only digging for the value, but figuring out how to add value. Thanks for sharing that. Dr. Streeter, what was this experience like for you?

Renee Streeter: It's always difficult to get a paper to finish. But honestly, I think it was really necessary and a little bit fun because before you undergo any prospective research, you really do want to be able to completely wrap your head around what's already been done and what do you need to look at.

So ,we couldn't have moved on until we did this, and why not write it up if we're going to do it anyway, right? So, I'm really glad we did it. I'm really glad it was the steppingstone into our prospective research that we were able to do.

Bradley Quest: I would completely echo everything Dr. Streeter said. It served a lot of purposes.

To build on what she said, first and foremost, was to educate us on the research that had been published. And help us to understand why things had been written, why things had been released, including the communications from the FDA. That was a big part of what we looked at, too, and trying to understand what kind of data and what kind of research those releases were based on, and then the other thing was as everybody else on our research team alluded to our ultimate goal was to do prospective research, but we wanted to understand everything that had been done and where we could identify what we felt like were gaps that really needed to be explored further.

Jordan Tyler: And on the topic of gaps, Dr. Clark, I'm curious if there were any particular gaps in the research that you found especially interesting?

Stephanie Clark: I think it's important to note that there will always be some sort of limitation or gaps in a study. That's how research builds on previous research. So good researchers should list the study's limitations in the discussion section, so those who want to repeat it can potentially address one of those limitations listed.

While we were doing our literature review, we noticed a few limitations. One was that there was an over-representation of particular breeds. There were a handful of studies that used the same breed of dogs, which makes it really hard to then apply that information to all breeds. Because it may be something specific to that breed.

Another limitation was the number of clinical studies and retrospective studies. While these are super important, they are extremely difficult to replicate, because they have a lot of uncontrolled variables that may have contributed to the results that were noted when looking at medical records for a retrospective study, it is impossible to decipher what treatment or part of the treatment was the result of the improvement. Was it medication, diet, medication and diet? What about supplementation?

Another example of uncontrolled variables in diet history—when I was working in clinic, diet history was challenging to get accurate. Whether it was feeding amounts, the brand, the flavor, additional treats and snacks. I mean, lots of things to consider. So, these retrospective studies that base definitive conclusions on diet history should be used with caution.

And for the last major limitation, there is a big gap in understanding the test diets. Studies that select a diet off the shelf do not know the inclusion percentage of the ingredients listed. So, to say something is “rich” in an ingredient based on the location within the ingredient list should also be used with a lot of caution. Additionally, there are studies that state a change from grain-free to grain-inclusive, but we don't have knowledge or any indication to what the omega-3 content is, what the amount of B vitamins, the sodium content, all these things can have an impact on the heart as well.

So, limitations are just part of science. But that's why good research leads to more research, because those limitations start to develop and then researchers can start to address them, just like we did with ours. We were able to formulate and understand the inclusion of the ingredients, we controlled for as many variables such as breed, genetics, and size of dog, and these were based on the gaps that we identified during our literature review.

Jordan Tyler: Yeah, thank you for sharing that because I think it reiterates the fact that this stuff is not easy. It can be extremely challenging to design a research study without some kind of limitation. And as researchers, you try to control as much as you can while being as thorough as you can. But limitations are just something that come with the territory.

Now kind of bringing this full circle, now that I'm all excited about limitations, Dr. Quest, what are your thoughts on limitations in the research and the data that informed the FDA's first few announcements?

Bradley Quest: That's a really good question, Jordan. And we've reviewed a lot of the information that we've received on this and what we found is that it's actually a relatively small sample size. Now, I'm not trying to discount any dogs that might be affected with an illness, regardless of what the cause of that was, but the information that the FDA received on the dogs actually came from very few sources when you get into it.

One of the important things that we found is that we didn't see a lot of representation from a lot of different areas. They were kind of concentrated to certain areas of the country where this information was coming from and being sent to the FDA. When you actually look at this information too, there's so many different confounding variables that we feel like it would be impossible to come up with a diagnosis or an etiology or the cause of a disease.

And then also that to truly have a diagnosis of DCM, a dog has to have an echocardiogram. That echocardiogram has to be evaluated by a veterinary cardiologist against standardized measurements. There's even some differences of opinion or differences of experience among cardiologists as far as how to interpret different data that they might receive on a specific dog.

And I know that because we've talked to so many of them and it's not necessarily saying that there's one right interpretation. As opposed to another one, but making sure that those are as standardized as possible is super important. And then of course, the thing that we try to look at very closely is diet history, because really, and truly, if you're trying to implicate diet as the cause or contributing to a disease process. You must be unequivocally adamant that diet history is accurate. And the problem we see with that is we do know that it's hard for pet parents to always remember that. But when you're using a diet history as the inclusion criteria in any kind of research, and you're relying on people's memories for that, and then you're relying on a researcher to collect that information in a standardized way, it can be really, really difficult.

But what we found when we looked at all of this is that it was lacking very much. So, Jordan, when you look at how this whole thing was handled, the public, pet parents, and veterinarians were asked to report cases of DCM that were suspected to be related to diet. What that did is that put the onus on pet parents, on general practicing veterinarians, and even on veterinary cardiologists to actually try to determine what the cause was of a specific dog's cardiology problems, or in this case, phenotype. We can tell you that there's nobody that can definitively tell you whether or not any diet categories are causative of DCM.

So, to ask for that, we felt like it contributed to a lot of sampling bias and really a lot of research bias. When we looked at a lot of the data that were shared with us, one of the things that stuck out too is the lack of long-term medical histories in a lot of these cases. In other words, some of them had very little to almost no medical history involved with it, at least what was shared with us.

Jordan Tyler: Yeah, and so when you combine the lack of longitudinal data with the biased questions that were being asked, it kind of creates a perfect storm for information to be misinterpreted.

Bradley Quest: I think you're right. And I think we've said this before that clinicians and folks out there in the field seeing medical cases on a daily basis when you start seeing things that maybe don't fit. It doesn't quite look right. Sometimes we just tend to go on and think, “Wow, that's kind of weird.” But then sometimes you start seeing a pattern. And possibly what may have happened here is we had some folks that thought they were seeing some patterns in clinical cases, which is actually really good to bring to light to share, but what we have to be really, really careful of is drawing conclusions from what we think are patterns without doing due diligence and objective research and trying to get larger sample sizes and involving more people into this before we actually draw these conclusions; that can ultimately cause a huge uproar and significantly impact what people feed their pets as well as a huge segment of the entire industry. And that's actually what this whole thing did.

Jordan Tyler: I think that's a fair statement. We're all trying to understand how to do the right thing. And that's really the basis of this literature review, identifying the gaps and really painting a more comprehensive picture of the issue and all the factors that go into it.

So, I mentioned earlier that this literature review is a highly cited and read paper, but notoriety doesn't typically always come without a fair amount of skepticism. So, it's not surprising that the paper wasn't always met with the friendliest of critics. Dr. Streeter, would you mind sharing a little bit about the diversity of reactions and responses to this paper once it was published?

Renee Streeter: I think the diversity of response was ranging from interest like happiness that a lot of the information was now kind of in one spot so you could hopefully formulate your own ideas and opinions as to what could be going on or what research needed to be forthcoming, to people saying we cherry picked the information we put in and left things out.

And so, of course, none of that was ever intentional, right? You don't go through a literature review and intentionally leave things out. So, I think it was people trying to protect what they believed was right and correct and feeling potentially that this paper challenged some of those thoughts. And so that was probably the reason for the great range of responses we got.

I don't know if it is vastly different from things other people experience with literature reviews in hot topic areas. It's probably pretty common, but from a personal standpoint, it was slightly unpleasant to have negative feedback, of course, right? But we learned from it, and we accepted it, and we moved forward with more research.

Jordan Tyler: Dr. Clark, what are your thoughts on how the public reacted to this literature review?

Stephanie Clark: It was interesting to have so much backlash or unpleasant comments on a research paper. It was board-invited. This was something that was asked of us and we took on the challenge to the best of our ability.

I do think it's important though, when we look back at how much it's been cited, how much it's been downloaded, despite all the mixed feelings that people had when reading it or reading parts of it, it did serve its purpose as a literature review. It provided a lot of basis and details to a very complex disease. My opinion is if it wasn't needed, it wouldn't have been read so much and it wouldn't have been cited. No one had to cite that in their papers, but it is still being cited. So, there are still some really good nuggets in there that people are using to fill those other literature and knowledge gaps.

The major thing that people should take away from this is this is a true literature review, meaning that we did not design a specific study with a controlled environment. We did not do our own stats on this. We were simply gathering all the information that is out there. And that this disease, DCM, is a very complex disease. There are a lot of different factors that can play into it, whether it's the breed, whether it's external or internal factors, it's a lot. And to say, “This is absolutely the only or the major cause,” I think it's still way too early. We don't know enough about this disease and all of the factors that can play into whether or not a dog is going to get this, whether it be my dog who had mitral valve disease and then over time develop DCM or is it genetic or like Dr. Quest was saying, myocarditis and infections or hypothyroidism, tons of different reasons why, and it could be a combination. We don't know, it's just part of science to continue as a learning, so we can best serve our pets in a veterinary setting.

Jordan Tyler: Totally agree. You said it perfectly—it's highly cited, widely read. So, even if people disagree with it, it has served its purpose as an informative piece of literature on this highly convoluted topic. So, thank you for that.

This about wraps up our behind the scenes on literature reviews. And specifically, the literature review BSM Partners conducted on DCM and dogs. I want to extend one last thank you to Dr. Shoveller and our amazing BSM Research team. For sharing their expertise and insights in this episode. If you'd like to read the literature review, it's linked in the show notes for this episode, alongside a few other episodes we mentioned throughout the conversation.

We also have all our DCM research published and available on our website at bsmpartners.net/research/DCM. Happy exploring!

Thank you for tuning in to Barking Mad, a podcast by BSM Partners. If you'd like to learn more about us, please visit our website at www.bsmpartners.net. Be the first to know about new episodes by subscribing to the podcast and share it with a friend. We'd like to thank our dedicated team, Ada-Miette Thomas, Neeley Bowden, Paige Lanier, Kait Wright, and Dr. Katy Miller. A special thanks to Lee Ann Hagerty and Michael Johnson. See you next time!