Veterinary Vertex
Veterinary Vertex is a weekly podcast that takes you behind the scenes of the clinical and research discoveries published in the Journal of the American Veterinary Medical Association (JAVMA) and the American Journal of Veterinary Research (AJVR). Tune in to learn about cutting-edge veterinary research and gain in-depth insights you won’t find anywhere else. Come away with knowledge you can put to use in your own practice – along with a healthy dose of inspiration to remind you what you love about veterinary medicine.
Veterinary Vertex
The Overlooked Electrolyte: How Low Chloride Impacts Survival in Dogs with Heart Failure
A single ion is changing how we read the story of canine heart failure. We sit down with cardiologist Dr. Darcy Adin and internist–nephrology researcher Dr. Autumn Harris to unpack why hypochloremia—once dismissed as collateral damage from diuretics—now stands out as a powerful predictor of survival in dogs with stable congestive heart failure. The conversation moves from physiology to practice, showing how chloride levels map to renin–angiotensin activation, diuretic resistance, and risk, and how that knowledge can guide smarter, earlier interventions.
We trace the research arc: early work that spotlighted chloride as more than a bystander, data linking low chloride to advanced disease stages and higher diuretic needs, and the pivotal finding that hypochloremia predicts outcomes even after controlling for other variables. Along the way, we break down renal salt sensing at the macula densa, why chloride depletion ramps up neurohormonal stress, and how this affects real dogs with mitral valve disease and congestive heart failure. If you manage CHF cases, this is practical cardiology and nephrology in lockstep.
Most importantly, we translate the science into steps you can use tomorrow. We talk thresholds and trend-watching, ensuring chloride is on every chemistry panel, covering RAS inhibition, adjusting diuretic strategies to spare chloride, and when to consider chloride supplementation. We also preview active trials targeting chloride to improve diuretic responsiveness, cut hospital time, and lift quality of life. Owners get a clear takeaway too: lab values are not just numbers; they’re signals that help personalize care and extend good days.
If you care for dogs with heart failure—or love one at home—this deep dive reframes a humble electrolyte as a crucial guide. Listen, share with your team, and help push the field forward. Enjoyed the conversation? Subscribe, leave a review, and tell us how you monitor chloride in your CHF workflow.
JAVMA article: https://doi.org/10.2460/javma.25.08.0526
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Welcome to Veterinary Vertex, the AVMA Journal's podcast, where we delve into behind-the-scenes look with manuscript authors. I'm editor-in-chief Lisa Fortier, joined by Associate Editor Sarah Wright. Hi everyone, and thanks for tuning in. Today we're discussing how moderate to severe hypochloremia is associated with shortened survival in dogs with stable congestive heart failure, with authors of the manuscript, Autumn and Darcy. Hey guys, thanks so much for being here with us today. Thanks for having us join today.
SPEAKER_02:Before we dive in, Autumn, can you share a little about your background and what brought you to cardiology? Sure. My background is in small animal internal medicine with a really strong focus on nephrology. And I've always been drawn to renal physiology and how the kidneys maintain homeostasis and how it adapts to stress and how relatively small pathologic shifts physiologic shifts, sorry, can have clinical consequences over time, particularly in chronic kidney disease. So as my career developed, it became increasingly clear that the kidneys rarely exist in isolation. So many of our patients with heart disease, especially those with congestive heart failure, are profoundly influenced by the kidneys, both because of the disease itself and because of the therapies we rely on to manage it, such as diuretics, RAS modulation, fluid balance, electrolyte handling. And these are all areas where the heart and kidneys are in constant dialogue. So that intersection is what really drew me into the cardiorenal research. And that's what led to my collaboration with Darcy, who's a veterinary cardiologist, and we're both clinician scientists who really care deeply about asking clinically relevant questions and trying to answer them.
SPEAKER_00:Yeah, nothing exists in isolation in biology. Darcy, the jab article we're discussing talks about how hypochloremia is actually a predictor of poor outcomes with dogs and congestive heart failure. What is the background? If you want to add anything to what Autumn just said, what's the background behind this research?
SPEAKER_01:I think for me that the background to the research really extends way back to my residency when I became interested in heart failure research under the mentorship of Dr. Mark Kittelson at UC Davis. And following that, I spent the first part of my career researching diuretics with a focus on optimizing them to administer them in the most effective way to decongest heart failure patients. So we were looking at CRI administration and alternative loop diuretics like torsamide. And really until recent years, both human and veterinary cardiologists accepted hypochloremia as a consequence of effective decongestion without any real adverse effects. Acknowledging that yes, potassium and sodium wasting was recognized as clinically important, but not necessarily chloride. And so this changed a few years ago, maybe 10, 15 years ago, when in both human and veterinary medicine, we started to recognize that chloride was becoming increasingly important to the effectiveness and diuretic resistance and RAS activation in patients with heart failure. And as testament to that, even if you look back at the papers 10 to 15 years ago, they didn't even report chloride. That's how unimportant it was thought to be. But we now recognize that hypoplaremia is probably the most important electrolyte derangement that we see in congestive heart failure, even more so than sodium. And this centers around its role in renal salt sensing and renin release through the juxtapurar apparatus in the kidney. And so, fast forward a little bit to when I was at NC State, we performed a study in 2019 that was one of the first ones to really highlight that hypochloremia was associated with advanced heart disease. So having a chloride level less than 103.5 was associated with our definition of stage D congestive heart failure. And this was really the first indication of its importance. And then shortly after that, another group showed that hypochloremia, even before ferrosamide was given, was important to importantly related to end uh endosine diuretic dose, sorry, that would be an indicator of disease severity. So having two groups come to similar conclusions really does lend credence to the finding that we are learning more about the importance of hypochloremia. And for me, the one of the most exciting and interesting things is that this is one area where veterinarian isn't lagging behind human medicine. We are going along at the same discovery rate. And in some ways, Autumn and I are looking at some things that have not yet been looked at in human medicine.
SPEAKER_00:So two follow-up questions to that. Uh, one would be you talked a lot about using the word associative, but you also showed that it's a predictor of congestive of responsiveness to heart failure.
SPEAKER_01:Yeah. So um it's definitely in our study, one of the exciting things we showed is that it is associative outcome. And it um it was uh the one thing that came out as important in our study, even when we controlled for other known influencers of outcome in heart failure patients. And so the mechanism still needs to be looked into. We have some hypotheses for that, but um it is a predictor of outcomes. And then other groups, ourselves and some other groups have shown that it's a predictor of advanced heart disease stage or diuretic responsiveness. Um, so all these things tie in together because those are the things that are associated with poor outcomes in dogs.
SPEAKER_00:You just mentioned that you guys are looking at a few other things that are advancing the field for both humans and veterinary medicine. Uh, and you want to give us any sneak peeks?
SPEAKER_02:Yeah, so some of the next steps that we're really kind of falling into are kind of two complementary tracks. So we're trying to get at a mechanistic understanding, but then also a clinical translation. Um, so on the mechanistic side, we want to kind of move beyond chloride as a prognostic um marker and better understand why it tracks with outcomes. Um, and so our leading hypothesis is that chloride reflects or contributes to neurohormonal dysregulation, particularly RAS activation. Um, and this sets the stage for a longer, a larger prospective study measuring chloride along RAS biomarkers across different heart failure states, um, from stable disease to refractory heart failure. Um, so we have some of those studies in the works. And then on the clinical side, one of the key questions becomes once hypochloremia is identified, does correcting it change outcomes? So can we change the clinical course? Um, so that opens the door to trials evaluating chloride-targeted interventions, whether through supplementation or diuretic strategy adjustments and assessing meaningful endpoints like diuretic responsiveness, how long they're in the hospitalization, quality of life and survival. And so we do have some studies also going on in that realm as well. Um and so this becomes especially relevant in refractory or diuretic resistant congestive heart failure, where correcting hypochloremia could become a practical tool for improving symptoms and control. Um, and while there's an important implementation step also, we need to define what those actionable chloride thresholds are. Um, so is it below the reference range or is it the hundred cutoff that we used in this study? Um, and trying to develop evidence-based guidance so these insights can be safely integrated into our everyday congestive heart failure management. Wow, fascinating work. So, Darcy, what are some of the key take-home messages you hope veterinarians will remember?
SPEAKER_01:Well, I think as we've been talking about, this is chloride is not something that has been on people's radar until just recently. And in fact, a lot of the biochemistry panels that are out there might not even include a chloride. So we really want our big take-home is that uh chloride's important. We should be looking at it. It can help us as a very simple biomarker on a chemistry panel to help to stratify a patient into a higher risk for poor outcomes category and might identify patients that we need to think about ways to um maybe bring that chloride back up. So we know that they're that the loop diuretics waste a lot of chloride. They waste twice as much chloride as sodium when we give them. And so if there are things that we can do just practically every day looking at our patient that will spare loop diuretics, then that might be helpful in those patients. So we're we look in our clinical practice, we look at a couple things. What are the non-diuretic approaches that we can use? Can we offload the heart a little bit more with other strategies? Um, since we have evidence that hypochloremia might activate the RAS, we would look to make sure those patients are covered in RAS inhibition. And then we are also, as Autumn mentioned, um in some studies looking at ways to supplement chloride or potentially use chloride-spearing diuretics. So those are all the things that I think would be takeaways that if we can look at a patient and identify them as a hypochloremic patient that's at greater risk for poor outcomes, maybe we can adjust their medications today to bring their chloride back up into what we think is a safer range.
SPEAKER_00:Autumn, looking back, what what really sparked your interest in congestive heart failure? Was it one of your own patients of animal, of a friend, or a client?
SPEAKER_02:Um I think one of our first insights into that was um is a Cavalier King Charles Faniel name Honey, um, that was in the hospital for a long time with um refractory congestive heart failure. Um and we had a unique opportunity with her because she was in the hospital for so long to look at chloride over time and to get some RAS measurements for her as well. And that we were able to see that there seemed to be a pretty close link or association between chloride and RAS activation, um, which really started to spark an interest in me with the crosstalk with the kidney in it being more of a marker of underlying like pathophysiology and things that were going on, and if that could apply to a larger group of patients. Um, and that's really what sparked us to, I think, start um down some of this research trial, or at least for me.
SPEAKER_00:That's great. Yeah, this sort of research isn't easy to do, especially using clinical cases. So, Darcy, what keeps you passionate about this topic today?
SPEAKER_01:Well, I'm a cardiologist, and mitral valve disease is the most common thing we see, and heart failure is the most common thing that we treat. It's our bread and butter as cardiologists. And so my, as Autumn mentioned, our our grounding is really in clinically important research, the kind that is going to change the patient that I treat tomorrow in the clinic. And so, since that is the most common case situation that I see, it keeps uh trying to improve the quality and quantity of life for those patients that I see on clinic floor is really what keeps me passionate about it. And then I I love the curiosity that Autumn and I have. This is why we work well together, because we are both passionate about um the next thing and figuring out the next why. And that uh it's really kept us grounded as we keep the patient at the center of that. So it's it's really the it all comes down to improving the lives of patients.
SPEAKER_02:So you both have shared a lot of really important information about heart failure, and now I want to really get down to what's one important take-home. What's gonna change the way a veterinarian is gonna treat their next CHF patient? So, Darcy, what is one piece of information the veterinarian should know about hypochloremia and congestive heart failure?
SPEAKER_01:Well, hypochloremia is not just an innocent um bystander effect of diuretics in heart failure patients. It's probably mechanistically important and it's um good that we are starting to pay attention to it because I think it gives us a target for intervention to change the outcome for those patients potentially.
SPEAKER_02:And for clients, Autumn, what's one thing you wish more people understood about this topic? Um, one thing that I wish um more pet owners understood is that lab values like chloride, they're not just numbers. So they're giving us important clues about how a pet's body is coping with their heart disease and its treatment, and that monitoring these values help us as veterinarians stay proactive, fine-tuning treatment and individualizing care. Um, and ultimately paying attention to these details help us support quality of life and helps pets with congestive heart failure do well for as long as possible.
SPEAKER_00:Thank you guys. I've learned a lot, as especially as an equine surgeon, reading your article and listening to you again today. So thank you for taking the time to be here with us. Thank you for having us. Yeah, thank you for having us. Before we wrap up, we like to have a little bit of fun uh with these questions. So either one of you or both can answer this. What is the most unexpected or hilarious thing an animal has ever done in your presence? Could be a veterinarian or as an owner or observer. Well, I have a couple cavaliers.
SPEAKER_01:Shocking, I know. And they are wonderful and they are lovable. Maybe not the smartest dog in the world, though. So our one will go up the stairs um to try to look behind the TV when there's animals on the TV. Um, so barking maniacally at the TV, but also trying to go behind it to see where they are. So I don't know though. Super weird necessarily, but it is amusing to watch.
SPEAKER_02:I have cats, shockingly, because chronic kidney disease researcher here. Um she is um obsessed with my daughter and they play with a little unicorn toy. And so whenever my daughter goes to school, she goes, she grabs that toy and goes to the door and like holds it in her mouth and watches her like walk to the bus stop every day. That's a little sad and precious.
SPEAKER_00:Darcy, back to you. If animals had job titles, what job would your favorite species, maybe your uh King Charles, uh, be surprisingly good at if maybe nothing?
SPEAKER_01:No, so our newest one is a seven-month-old cabbie now, and he's possibly the cutest thing ever. Um, we call him baby dog, but he is a one one dog well-being movement. So you can go home after whatever day you had, and he is an effective therapist. So I'm pretty sure that's his job.
SPEAKER_02:Very good. Autumn, how about you? Oh, my cat's the chaos coordinator. She likes to keep my daughter in line. It's hilarious.
SPEAKER_00:Great job titles and fun jobs.
SPEAKER_02:Oh my gosh, I love both of those. Well, again, Autumn and Barcy, thank you so much for joining us. And for our listeners and viewers, you can read Autumn and Darcy's article in JAPMA. I'm Sarah Wright here with Lisa Fortier. Be sure to tune in next week for another episode of Veterinary Vertex. And don't forget to leave us a rating and review on IPA Podcasts or wherever you listen.
