Good evening everybody and welcome to a Thursday night members webinar. My name is Bruce Stevenson and I have the privilege and honour to be chairing what promises to be a fascinating presentation with Andrew on an update on canine dilated cardiomyopathies. Just before we get started, I don't think we've got any new people on tonight, but just in case we have, if you have any questions for Andrew, please feel free just to drop them into the Q&A box and, as usual, we will hold them all over to the end.

And then Andrew has very kindly agreed to stay and go through those with us. So Andrew started out in mixed practise in North Cornwall before leaving the beach behind and moving to the beautiful city of Edinburgh to complete his specialist training in small animal veterinary cardiology. Since being awarded his ECVIMCA diploma in small animal cardiology in 2013, he has worked in the pharmaceutical industry and specialist referral practises where he was head of cardiology at Anderson Moore's Veterinary Specialist.

Andrew now runs his own specialist, specialist visiting cardiology company in the South Coast called South Coast Cardiology with regular clinics in general practises across the south of England as well as into Belfast and Glasgow. So it's a nice wide travel area for you Andrew. Welcome to the webinar and it's over to you.

Thank you very much, Bruce. Thank you for taking the time, everyone, to, for those of you down south on a beautiful summer evening, but I think for those of you further north, a bit of a rough day. But thank you all the same for taking the time out of your precious, evenings, to come and join us to.

Have a look at, where we are with canine dilated cardiomyopathy. Now, I appreciate that for some of you, particularly those of you with an interest in cardiology or those that maybe have a, a proactive, boeing a rep in your territory, that you may well have heard some of this information, but the aim is to try and give you an update of how the changes, to the recent data of how we manage dilated cardiomyopathy has pretty much fundamentally changed when we, intervene with medications, and that that's actually had quite a profound effect on survival time. So Bruce very kindly introduced me, but just, to cover a few, elements, so I'm a European and Royal College recognised specialist.

I've got various clinical expertise in university and, private specialist cardiology settings. I have previously worked in the past, now pretty much the distant past for Boeing Engelheim, and I also have done a commercial advisory for both companies, so that's, a conflict, any conflict of interest is declared there. In terms of what I would like to cover over the next 45 minutes or so, we'll have a quick look at disease overview.

We'll focus a good part of our time on making the diagnosis and picking up, the dogs that are more likely to have DCM. We'll have a quick look at what the current treatment pathway is, and when I mean current, I mean, some of you may have already changed what you do, but it's, certainly in my experience of giving, CPD talks, quite a lot of people haven't necessarily changed how they manage, their cases. So far.

We'll have a look at the major change, the PTE study, which very much changes how we now er manage this disease. We'll see what, if any, new treatment recommendations come from the results of that study. And then we'll answer the, the rather thorny issue of screening, and are there any screening guidelines?

Should we be proactively screening perfectly healthy animals? I think some of those will remain questions that are, don't have an answer, but I think we will try to address them towards the end. So first poll question, just to get an idea, from the members attending tonight, which disease do you feel is more common, acquired disease is more common in doctors is delayed cardiomyopathy or mitral valve disease?

Right guys, you know what to do. Just simply click on the answer that best suits your opinion. It is completely anonymous, so, please don't feel like there's any form of threat to it.

Just give us your opinion and we'll show those answers in about 30 seconds or so and let Andrew see what the decisions are. That's it, nice and fast. Voting coming in here.

We've got a couple of stragglers, we'll just give them a bit of time. 10 more seconds guys, and then we're gonna close the poll. Right, let's close that poll and share the results with you, Andrew.

There you go. OK, so, yeah, so I think that, that, generally fits with, I think people's understanding. Is that, mitral valve disease is absolutely far and away by a country mile more common than, than dilated cardiomyopathy.

So, obviously, the answer is that mitral valve disease is far more common. Now, to put some numbers to that, because obviously these are both acquired conditions that we talk about quite regularly, actually, they both have similar treatments in the earlier stage with Pimirendan. But what is the difference in terms of, of a prevalence?

Well, DCM is actually relatively rare. So the overall prevalence is around about 0.5%, and most of those patients will develop congestive heart failure.

A slightly higher incidence in pedigree dogs and cross breed dogs, which reflects a genetic component. Large and giant breed dogs are at greater risk. Greater risk is with increasing age, and males are certainly more affected than females, particularly with progression to congestive heart failure.

So the take home message with DCM is, although it is a pretty catastrophic disease, when it's there, it's relatively rare. Conversely, mitral valve disease is spectacularly common. In fact, most dogs have valvular changes.

So the question is, in most dogs, is it just a normal age-related age-related degenerative change rather than a pathological disease process? And is it just in the really high risk breeds like cavies and daxis that they have an actual disease and the short answer is we don't really know the answer. .

Around about 30% of dogs with much valve disease will progress to develop congestive heart failure, and, but the vast majority do not develop congestive heart failure. So the majority of your 789, 10 year old dogs plus, with a mitral murmur, will have mitral valve disease, and it will be hundreds of them, but most will never have an issue with that disease. Whereas conversely with dilated cardiomyopathy, it's much rarer, but when the diagnosis is correct, they will nearly always die of that disease.

So to give you a summary, dilated cardiomyopathy, low prevalence mitral valve disease, very, very high, ease of diagnosis, well, DCM is hard because you have to identify the stolic dysfunction, and we'll come to that in a minute. Mitral valve disease, diagnosis is actually quite easy. You get the characteristic murmur and, and then you're looking for valvular changes.

So in most cases, the diagnosis mitral valve disease is relatively straightforward. The progression rate, DCM pretty much 100%, if you've got the right diagnosis, mitral valve disease, 30% overall will progress, so 70% of all dogs with mitral valve disease will not progress ever in their lifetime. However, in the at-risk breeds like Cavalier King Charles Spaniels, then that progression rate can be up to 90%.

Disease degeneration in DCM 2 to 3 years, mitral valve disease potentially 3 to 5 years plus. So the take home message is DCM is less common than mitral valve disease by a significant margin, but it's much harder to pick up and diagnose, and that's what we're gonna focus on, in a little while when we focus on diagnosis. So what is dilated cardiomyopathy?

Well, in its most essential form, it's a primary myocardial heart muscle disease and it's a primary decrease in contractility of one or both ventricles. So that decrease in systolic function happens before the heart dilates. The problem is, is that in many cases we only pick up the disease when they've already dilated.

So we then classically see a very dilated heart with poor contractility. But the poor contractility comes first. And the reason why that's important is because when we look later at the Protect study, you'll see that the inclusion criteria were very subtle changes in contractility.

What causes the lates cardiomyopathy? Well, this is, a difficult one. There are multiple causes.

We appreciate genetic causes to be the major issue in dogs, but in humans, that's only 20 to 40% of cases. And actually, the majority of cases in humans are non-genetic, and a very common one in humans is a viral myocarditis. So people who often end up on the transplant list have A, a viral infection that, if they're unlucky enough, seeds in their myocardium, and they then get essentially a low ejection fraction or a poor systolic function, heart failure over time that ultimately results in them requiring a, a heart transplant.

Other causes, nutritional, so we do see that rarely. I've seen a couple of cases in dogs, particularly with the move now to, feeding more atypical diets in some cases. I have seen a couple of cases, nutritional cardiomyopathy.

They're usually associated with taurine deficiency. The classic toxic cause, would be any, drug, any, any, toxin that affects historic function. Now, the problem with the toxic cause is that you very rarely will be able to, pick up the underlying toxic cause, because by the time it's had its Negative effect is usually many months in the past.

The classic drug-induced version was doxorubicin-induced, and then we have quite a good portion that we class as idiopathic because we either don't do myocardial biopsy and prove viral involvement, or we don't have adequate genetic testing. But it is generally perceived that the majority of cases in dogs, and that's why it tracks breeds, are probably have some form of genetic cause, though I do think we are underestimating or even just not looking at all for the viral, associated DCMs. Commonly affected breeds.

So this is, these are generally commonly accepted breeds, that are prone, to dilated cardiomyopathy. There are some, there are some, slight differences in the phenotype or, or the way the disease presents. So, In Irish wolfhounds, and to some degree, Great Danes, they will sometimes get atrial fibrillation for prolonged periods of time before they get any cardiac changes.

And there is some debate as to whether the atrial fibrillation causes the dilation or whether it's just an early clinical sign of their form of DCM. Dobermans, the problem with Dobermans is they get horrible arrhythmias. So around about 30% of Dobermans that have DCM, their first clinical sign will be sudden cardiac death.

So, Dobermans have a very proorhythmic form, and other large breeds, although they can have nasty arrhythmias, seem to be less prorhythmic. And then the other one. That stands out is the cocker and springer spaniels, seem to get a form of DCM which seems to be a bit more slowly progressive than in some of the other breeds.

So it's clearly DCM, it behaves like DCM, it looks like DCM, but it seems to be a bit more slowly progressive. And there is some data in American cocker spaniels of the of taurine deficient di cardiomyopathy. I'm not aware that that's ever been categorically proved in the English cocker spaniel in our cohort in Europe and in the UK.

But it's certainly something to bear in mind in your cocker spaniels if you see them with DCM. So typical disease pathway, er, as we said before, the primary issue is histolic dysfunction, so that's what happens at the beginning. Then you'll often find there's a long silent period, where there are no clinical signs noted, but will often, if you look very, very carefully.

See silent arrhythmias or very low grade variable murmurs. Domans, as we mentioned on the last slide, they're unlucky in a good portion of those, suffer sudden cardiac death way before they develop heart failure, but not that many other breeds behave like that. I know with other.

Breeds behave just like that. So that's really a quirk of Dobermans. The other, breeds, they tend to sort of carry on in the pre-clinical phase.

If the owner is very diligent, they might notice excise intolerance, but ultimately, often the clinical signs that we see are consistent with congestive heart failure. And then if you look at the colours of the arrow, then the pre, basically the pre-symptomatic or phase can last 2 to 3 years. And actually, the, traditionally, the period of time we used to treat them was survival times of 2 to 4 months with a 90% year one fatality rate, and that's because we've always been treating them very late on in the disease process.

. So, some, a staging system that some of you may have come across, which we, was presented, it tends to be presented and associated with mitral valve disease, but it can actually be used for any cardiac disease and actually is quite a useful. To use in other cardiac diseases. So all breeds, that are at risk going to stage A.

So that would be all the ones on my list of, of recognised breeds. The stage B one for DCM would be heart disease present. And I'll, I'll just show you on the next slide how that will be specific for, DCM.

Stage B2 is heart disease present, but the heart is now bigger than it should be. Stage 3 is congestive heart failure, past or current. So any previous history or current history of congestive heart failure, and stage D is heart failure, which is now refractory to standard treatment, and that tends to be, freeze my doses above 6 mg per kg BID.

If we map that on to DCM then the stage A groups, your Dobermans, your Labradors, your at-risk breeds, etc. Your B1 is any dog with mild systolic dysfunction, but otherwise normal heart size, and they may have arrhythmias, they may have murmurs, but they may not. Stage B2 is your systolic dysfunction and Your cardiomegaly, Stage C is your heart failure associated with your DCM and stage D is the end stage.

So what you find is the obvious clinical signs are usually happening somewhere between the early onset of stage B, of stage C or the later on, the later stages of stage B2. And what we'll see, we, we'll use this slide, to map, where we used to treat and now where we are with the results of the ProTE study, advocating treatment, moving forward. So this slide will come back again, a bit later on.

So, we'll now have a quick look at clinical presentation. So, presenting clinical signs, and the vast majority of, of, of dogs in the pre-clinical phase, the dog is asymptomatic or at least asymptomatic from the owner's perspective. For over DCM we're basically looking at clinical signs consistent with congestive heart failure, so that's your tachy mere dysia, exercise intolerance, weight loss, abdominal distension, if there's right side involvement, syncope, sudden cardiac death, and or coughing.

In terms of physical examination for your pre-clinical dogs, then these are often, you know, the owner does not perceive any kind of problem, and you may well pick up a normal physical examination. But if you are going to pick up abnormalities, they're likely to be subtle. So, a low grade histolic heart murmur, if they're present with DCM they're usually less than grade 3 out of 6, so they're usually grade 1, grade 2, those kind of grades.

You may hear some form of third heart sounds, so a diastolic gallop or a gallop rhythm. And you may get arrhythmias. Now those arrhythmias could be obvious like atrial fibrillation, but they could just be one single premature beat.

And as you'll appreciate when we see that we're trying to pick these dogs up at the earliest stage of, of systolic dysfunction. The take-home message from physical examination is that in those at-risk breeds, very subtle cardiovascular abnormalities should not be ignored as nothing to worry about. So whereas you're quite within, you know, it's quite, I'm quite happy if, you know, I auscultate a grade 1 or grade 2 heart murmur in a cavity, the client's not interested in doing anything, and I'm quite happy to, to re-auuscultate in a few months' time.

If I have a Doberman, say, or a large breed dog with a, with a soft systolic murmur, then I'm much more concerned this dog may have delay cardiomyopathy. And because you don't have the classic murmur to follow, you often need to investigate these dogs much, you know, when they, when they have clinical signs of abnormalities of physical examination, that you might initially feel to be potentially inconsequential. Physical examination when you have overt symptomatic DCM is, much less challenging because you're gonna have overt clinical signs consistent with congestive heart failure, and or forward failure.

So most dogs tend to present in left-sided congestive heart failure, and congestive heart failure are the clinical signs that tend to predominate. If you're unlucky, or if the animal presents very acutely, then they can present with forward failure, and these are the patients that present collapse, low blood pressure, hypothermia, weak pulses, poor perfusion, cold extremities. Now, the key thing to bear in mind with forward failure patients is that they've nearly always had a history of backward failure or congestive heart failure first.

So, obviously other potential differentials for forward failure would include other circulatory disturbance, blood loss, shock, trauma. So there are plenty of non-cariac causes of, of clinical signs consistent with forward failure. So the thing to look for in the history, if you're concerned about a patient with hypothermia, weak pulses, palmucous membranes, cold extremities, etc.

Is that there's usually in the history, some, understanding of congestive failure first. So it might be a cough, it might be excise intolerance, it might be sort of elevated breathing rate. So it's definitely, one to bear in mind when you have a patient that looks like it presents with just forward failure.

We're now gonna spend a bit of time focusing on diagnosis. Now, this will, depend on, to some degree, your individual level of expertise with ultrasound. So I'll focus on this as we go and flag up those subtle changes that you would, I think a lot of people would struggle to identify unless they do a lot of ultrasound.

And, and in those situations where with dogs with quite advanced disease, you're gonna be able to pick them up quite easily with relatively basic ecos skills. In terms of diagnostic tests for diagnosis itself, then really the only definitive test for diagnosis is echocardiography, and that's why I've highlighted it in green. So, I haven't highlighted ECG or biochemistry haematology because they have no diagnostic value.

They might have contributory value, in terms of looking for other organ damage or with ECGs looking for chamber enlargement, although sensitivity and specificity of ECG for chamber enlargement is pretty low. The thing to bear in mind is that thoracic radiography and biomarkers, so biomarkers allow you to assess whether the heart is dilated, but they will not tell you whether the heart has early stage systolic dysfunction. Thoracic radiography will tell you whether the heart is big or not, but again, it won't tell you whether this dog has primary DCM or another cause of its dilation.

The only way to definitively diagnose DCM is with echocardiography. So, when we get to the PTE study, we will see that those measurements are very subtle. But actually, for the cases that are probably gonna present you with clinical problems, so they're the ones that either have been unlucky enough not to have even very subtle clinical changes.

So they've been completely silent, and in those cases, often unless you're proactively screening all your large breed dogs, which is difficult to justify at this stage, you're gonna pick up cases which are overtly abnormal. Then actually the 2D findings you'll find on, on Echo are actually relatively easy to pick up even with relatively rudimentary echo skills. And the key thing to remember is systolic dysfunction first, OK?

So the typical 2D findings are impaired systolic function, dilated left ventricle, or rounded left ventricle. So the two still images on the screen. You've got the big, you've got the dilated left ventricle here.

And obviously, with a 2D image, it's very difficult to assess, a still image systolic function, because that's a, a beat to be active process. But if you do have an M mode, then you'll see that there's very little septal motion and very little free wall motion. So to me, that immediately looks like a dog that's both dilated and has poor systolic function.

So, we're now just gonna focus on a couple of the key attributes. So you have a globoid left ventricle. A big left atrium and poor systolic function.

OK, so that heart is big, and normally if a heart was that big with normal systolic function, I expect it to be pump the muscle walls to be moving significantly, but that is not moving very much, . We also talk about, there's all this talk about what a globoid left ventricle. Now, the normal heart on the left is a classic normal human heart, and you can appreciate that the ventricular chamber is much more bean shaped or at least elongated than, and that's a normal shape.

So when we talk about remodelling or globoid left ventricle, you can see in the right hand image that the left ventricle has completely changed in shape. To accommodate the volume change associated with dilatory. So systolic dysfunction first, but because the systolic dysfunction compromises output, the body increases blood volume to compensate, and the heart has to get bigger to accommodate that increased blood volume.

So it dilates, and when it dilates, its shape changes completely from nice, thin and bean shaped to round and circular. So that's what we mean by a globoid left ventricle. If we compare it with mitral valve disease, this is a dog with severe mitral valve disease, so they've both got massive left atria, but you can immediately see the difference.

That, that wall motion of that left ventricle is pretty pronounced. So dogs with mitral valve disease tend to have much more pronounced wall motion, because, they've got the release valve of all that blood volume can shoot back into the relatively low pressure left atrium. Whereas with DCM, at least in the earlier stages, they've got to pump most of that blood forward into the high pressure aorta.

So adult with DCM, the heart actually has to work a lot harder than it does in the earlier stages of mal disease. So this is back to that image before, the dog with DCM so you can appreciate that that wall motion, although there is some wall motion, it's not moving nearly as much as the the Mike Traval's dog was. The other thing to appreciate is in this view, the left ventricle.

Does look subjectively bigger than the left atrium. So this is another rule of thumb. It doesn't work in every case, but it's a good rule of thumb.

If the left ventricle is appreciably bigger than the left atrium, it's probably more likely to be micro to be dilated cardiomyopathy and conversely. With mitral valve disease, the left atrium is often the bigger chamber in the left ventricle, and that is because it's receiving all that regurgitant blood, as well as receiving all the normal blood from the pulmonary vein. So it is the chamber under most dilatory pressure in mitral valve disease.

So classically in mitral valve disease, the left atrium is often. Objectively bigger than the left ventricle. So I'm just trying to point out some obvious 2D changes that will help you differentiate between the two.

The thing to bear in mind with, with dogs that are this dilated is that both dogs with dilated ventricles due to DCM and dilated ventricles due to mitral valve disease, Pyman has indicated in both cases. So as long as the heart is big and abnormal, then actually, whether it's marginalities and DCM is a bit less important because now that actually the intervention point that what we treat them with, is the same. So I wouldn't get too worried, but it's actually relatively easy with a bit of practise to identify obvious DCMs and obvious mitral disease and to differentiate between the two.

So, this is an M mode of the dog with mitral valve disease, and I've highlighted the diastolic measurement here. So this just is the measurement of the biggest size of the left ventricle in diastole. And we measure this against reference ranges that are for the, for the breeds and for the weight, and, as soon as this is grossly more than normal, then it, then we can say that the heart is dilated, it's bigger than it should be, it's volume loaded.

But what you can appreciate, even if you make no measurements, is that there's very, very little wall motion of the septum and very relatively little wall motion of the free wall. The other measurement we make is we take the systolic measurement, which, strictly speaking, you can, you can approximate with the, with the minimum measurement. we use the ECG to check that we know we're definitely doing the systolic measurement, but in general, you can just pick the minimum measurement, and this gives you, as, and when this.

Single measurement, the internal diameter in cystole is above the reference range, then that dog has systolic dysfunction. OK, so you can appreciate in this dog that just subjectively, the diastolic diameter and the stolic diameter are both elevated, which means we have systolic dysfunction and we have volume overload. So therefore we have dilated cardiomyopathy.

This gives you the difference. I'm gonna flick back a, a, a slide again. So this is DCM, this is mitral valve disease.

So even with quite significant mitral valve disease, until the very end stages, the left ventricular wall motion is quite hyperdynamic, it moves a lot, so you can very quickly appreciate the difference. If you put the M mode on and you see this DCM is much, much more likely. If you put the M mode on and you see this, then.

Mitral valve disease is by far the most likely differential. The other thing is leaflet changes. So this is back again with the dog with DCM, so you can appreciate that those leaflets, you may not have seen many leaflets before, but they're thin.

They don't, they're not unduly thickened at the edges, relatively normal looking valves. Compare that with mitral valve disease, and these clubs shaped lesions on the end of the valve are the characteristic mitral valve changes. So relatively little leaflets, changes, quite obvious characteristic mitral valve changes.

And then there's one more thing that can help you differentiate. Remember that in dogs with dilated cardiomyopathy, systolic dysfunction comes first. Therefore, mitral regurgitation, if it is there, is a secondary thing.

So what you'll often find is you'll put colour on the mitral regurgitation and you'll go, well that doesn't look enough to explain the fact that the heart is massive, and that's because it's a secondary effect of the heart being dilated. Whereas with mitral valve disease, the leaky valve is the primary defect. So in many cases, the degree of mitral regurgitation visible on colour Doppler will directly track the severity of the disease.

So you can immediately see in this dog with severe m regurgitation so much of our disease, that the mitral regurgitation is pretty significant. And fits with the size of the left ocean, the size of the ventricle, whereas with DCM let me go back one more just so we can make that work again, it's actually a relatively subtle amount and doesn't really explain the other signs you're hearing, you're seeing. So I think with a little bit of .

Practise, I think you absolutely can identify dogs with obvious mitral valve disease and obvious DCM in general practise and differentiate between the two. The key driver of everything in all the diseases we really manage is left atrial size. And, actually getting used to measuring left atrial size on this short axis view, is certainly doable with a bit of practise as well.

In the UK and in Europe, we tend to use these short axis measurements. So there were two main versions, as you can see on the screen. And the cutoff for these short axis measurements is 1.59 to 1.

So the left atrium. Can be a maximum of 1.59 times the size of the aorta.

The key thing to remember is that, just make sure that the reference range you're using reflects the, the, method you're using for measuring left atrial size. Some books, particularly books, American textbooks, talk about measuring left atrium in the long axis, and there's no, no problem with doing that, but it will be a different reference range to the one presented here. I think the key thing to bear in mind for any of you who are doing Echo or are starting to do Echo is that the hardest cases are always the ones that are subtly abnormal, because telling the difference from a normal dog and a mildly abnormal dog is very difficult, and takes years of practise.

But telling the difference between a normal dog and a grossly abnormal dog is actually pretty, easy to do with a bit of practise. So, . You know, I think for guys looking to, use more echo to identify these patients in practise, you're gonna struggle to identify the very early stages of systolic dysfunction, but you're absolutely going to be able to pick up the dogs with more significant disease and the ones that potentially have the most clinical signs reported by the owner.

So, another option you have is to identify cardiogaling, because we've just said that a big left ventricle and a big left atrium, is an indication for pendan treatment in both micro valve disease and dilated cardiomyopathy. So one option you have is to try and identify cardiomegaly and then base your treatment decision based on that. And you'll see that reflected in the different.

We'll, we'll touch on the licence and, and how the licence, changes in mitral valel disease and dilated cardiomopathy, but the licence for the pre-clinical use of immerendan in DCM actually specifies echocardiography, and the reason it does is because you can't pick up the early stages, as I said before, of histoic dysfunction without using echo. However, you can identify carddiomegaly. Echocardiography is still the best test at identifying the early stages of cardiomegaly.

But here, biomarkers thoracic radiography are more useful than they were for diagnosis. So thoracic radiography and biomarkers can absolutely identify patients with carddiomegaly. Electrocardiography, I have put in red because strictly speaking, ECG changes can give you ideas of chamber enlargement, but in, depending on the measurements you make, the sensitivity and specificity can hover around the 50% mark, and it's worth bearing in mind that the sensitivity and specificity of 50% is the same as tossing a coin.

So if any diagnostic test you're using has a sensitive to your specificity close to 50%, you could probably argue it's not worth running. So I would be careful with ECG. So for me, ECG abnormalities are a reason to do another diagnostic test to prove whether they're right or not.

I wouldn't rely on ECG in any shape or form to identify cardiogaly by itself. And again, the reason why biochemistry and haematology is in black is because there's no real way of them helping you identify whether a patient has cardioomegaly or not. Quick look at radiography.

It's very useful for evaluation of general cardiac size in DCM. You can use a diagnosis specific chamber enlargements, but echo is always more accurate, but that will depend on how good you are at echoing them. So, if you have done echo for many years, then, .

Echocardiography is absolutely always the best test for diagnosing specific chamber enlargements, but if you have no echo skills whatsoever, then you could argue that probably radiography is gonna be more accurate in your hands than trying to do your first echo on that patient. Radiography, is obviously also useful for the diagnostic congestive heart failure, for, Ruling in or out, non-cardiac, mainly respiratory disease. And it can also be useful for, monitoring the effort because you have congestive heart failure therapy.

So, re-adiographing them after, a period of time on heart failure medication, in the acute phase to check that you have achieved the reduction in, pulmonary edoema that you think you have. So those would be the main indications for radiography in dogs with DCM. I think the thing to bear in mind er with .

Using radiography, is it the vertical heart score or vertical heart scale. Gives you a global, assessment of cardiac size. This is the standard, way it's measured on the screen at the moment.

And it definitely has its uses, but you need to be careful with measurements that are, subtly more than the reference range. For a number of reasons. The first reason is there is significant breed variation.

So this gives you an idea of some of the breed variation, that we see. So if you were to use a broad cutoff of 9 of 10.5, then you might be missing some GSDs with German shepherds with dilation, but conversely, most Labradors you will pick up as being abnormal, most whippets you'd be picking up as abnormal, and those cabbies you'd be picking up as abnormal, even if they were normal.

And look at the boxer, revertible hearts go up to 11.6 is normal, . In In boxes.

The other thing to bear in mind is that respiratory and cardiac cycles can affect the vertebral heart scale by up to 0.97 vertebral units of vertebral bodies and 1.1 respectively.

And there is also a variability between observers. So if you look at the radiograph and your colleague looks at the radiograph, there could be a variability of up to one vertical body. So it's just something to bear in mind in certainly in my sort of take home message with Thoracic radiography for diagnosing chamber enlargements is it's pretty useless for the very early stages, but very useful, with the dogs in the later stages of cardiac dilation.

NT Pro BMP, NT Pro BMP is a very interesting, biomarker. I think it definitely has its uses and it will progressively have more uses. But I think, one of the problems we have.

Is that a lot of the, of the studies that's proven its efficacy are used in in screened populations of dogs where you they are either have cardiac disease or have no cardiac disease and have had other diseases screened out. So it's a little bit of a rarefied population. If you then test NTR BMP on a varied population of dogs, it doesn't perform quite so well.

And the other thing I think we need to bear in mind is that the thing that we are now starting to realise is that in dogs, because we, we are dealing with a breed, size range from sort of 2 kg Chihuahuas to. 70, 80 kg Irish wolfhounds, Great Danes, that actually potentially is the NT Pro BMP value gonna be the same in all dogs at those varying weight ranges. There is already some evidence to suggest that Labradors have a different, Reference range for NT Pro BMP.

So I think at this stage, we need to be careful how we interpret it, but I think NTRMP does have a place in trying to identify those dogs that might be at risk of DCM and therefore might, might be sensible to look a bit closer at them in terms of, Further diagnostics. So this is the next poll question, so I just thought I'd pop a quick ECG in and see what you guys think about the ECG diagnosis for this ECG in front of you. But Andrew, I'm going to hold off launching the poll just because it will block the view of the ECG so we'll just give them a little while to have a look at that folks, we'll just give you a couple of more seconds to look at those ECGs and then I will launch the poll.

Right, let's launch the poll. So your options are atrial flutter, sinus tachycardia, atrial fibrillation, sinus rhythm, ventricular tachycardia. It's quite a varied variable set of answers you're going to get Andrew.

That's fair enough. Right, it is a difficult one to answer, so I'm just going to give a little bit. Alright folks, another 10 seconds to answer and then we're going to end the poll.

Right, let's end that poll and show you the results. OK, exactly as I expected and that's partly why I put it in. So, the, the, the major, the majority answer, atrial fibrillation is the correct answer.

sometimes it is really hard to identify atrial fibrillation on, an ECG. Classically, it's a supraventricular rhythm, so, the complexes are, the QRS complex are of normal duration, so they're not wide and bizarre, but obviously if you've not seen the dog in normal sinus rhythm, that can be hard to say. With no appreciable P-wave activity.

And, and there is no appreciable, P wave activity in this image, but sometimes it's difficult to see because there might be the fibrillation waves or wandering baselines, so it can be very difficult. The key thing with atrial fibrillation is the chaotic rhythm. So when you listen to these dogs, the rhythm will be completely unpredictable.

People call it, trainers in a tumble dryer. Or bongo drums. It's completely, chaotic.

Therefore, if you're unsure, go back and listen to the dog again, because quite often, your ear is able to pick up the chaotic rhythm more than your eye is on the screen, OK? so, the reality is, it is atrial fibrillation, and the reason I put that in is because it is by far the commonest, rhythm associated with DCM in dogs. And that partly reflects the fact that we're dealing with larger breed dogs which have bigger atria anyway, you need bigger atria to be able to support atrial fibrillation, and then they get big atria because of their DCM so atrial fibrillation is very common.

What you'll find in smaller breed dogs is that because their hearts are much smaller, if they do get atrial fibrillation, it tends to be right towards the end of the disease process, so almost the end stage of mitral valve disease, whereas lots of large breed dogs, will actually get atrial fibrillation relatively early on in the disease process. Andrew, have we lost you? Mm.

Andrew, if you can hear me, I think you are muted at this stage. Folks, we seem to have a bit of a technical issue. If you just bear with us, we will get Andrew on the phone and And we will deal with this as quick as we can.

I'm just going to give him a call and see if we can get him back on the line again. Bear with us a second, please. Bruce, it's OK, I will ring him, so you just do a song and dance routine.

OK, fair enough. . So we'll just just get And get Anthony to, to call Andrew and see if we can get him back on the line again.

These technical things do happen when we have internet live broadcasts. And, if we, if we can't get his screen back up and running, it's not a problem. We do have a plan B in place where we can carry on with the presentation and we'll just get him up on the phone.

So it's not it's not a a a major train smash for us yet. Just an insecure connection, Bruce, you know, it's the, it's the wild south, the underdeveloped. I'm back.

I'm back. And it's all good. It's all good.

I will keep going on this for now because I think it will be better, but if we have a problem, I will. Yeah, no, it should be fine, just probably going back a tiny bit over to you, Bruce. So, I don't know where we left it, but basically I'd just moved on, we, I talked about arrhythmias in DCM and then we just started on the current treatment pathway.

Now, for some of you, the treatment pathway may still already beybend done in the early stages, but classically the treatment pathway has been. Andrew, sorry if I can interrupt you. We lost you just as we had finished the poll on the ECG.

Fine, so, OK, so, what I was saying about the result of atrial fibrillation is it's the commonest rhythm abnormality in DCM and that reflects the fact that you've got large breed dogs, with, large left atria. And therefore, they're more likely to have atrial fibrillation. The key thing is, if you're not sure if it's atrial fibrillation, go back and listen to the dog's heart again because quite often you can pick up the irregularity more by listening than you can by looking on the screen.

So that's just a little tip in terms of atrial fibrillation. The key take home message with arrhythmias in DCM is that atrial fibrillation is by far the most common. Ventricular arrhythmias do occur.

They're a big issue in Dobermans and to a lesser extent in boxers, but they're less of an issue in other large breed dogs, . We then moved on to talk, I then moved on to talking about the current treatment pathway. And this is the same disease pathway, and what we've traditionally done is treated them at the end stage of the disease with freezamidepibendam, ACE inhibitors, ronolactone, and other medications.

And that's what we've always done. And so if we map that on our, ACVIM modified scoring system, we're treating them at the onset of stage C, so, onset of congestive heart failure. And we know in, and we know in, we know in, dogs with DCM that the onset of stage C to death can be relatively rapid.

So what we're gonna try and do is see whether treating them earlier makes a difference. But if we're going to treat them earlier, then obviously we need to change our decision pathway from watching and waiting to intervening early. So, essentially, in terms of what's new was the PTE study, and I'm sure many of you have heard of this study before, we're not gonna go through it in any great detail, but we're just gonna give you the, the kind of highlights.

So, a randomised placebo-controlled study in Dobermans only, 39 in the Pim Bendan group, 37 in the placebo group. Primary endpoint was sudden death or onset of congestive heart failure. The secondary endpoint was time to death from all causes.

The inclusion criteria was that internal diameter and systole measurement, so the single M mode measurement above the reference range. Nothing else. OK, what we'll see is also there were lots of exclusion criteria, so if you found anything else abnormal, you would rule them out, but actually the only inclusion criteria was a single M mode, echo measurement.

This was it. That single internal diameter insisttole measurement was the only major inclusion criteria for these Dobermans in this study. .

And essentially what the PTE study asked is if we move Pyma Ben down right to the early stages of stage B1, so just when they develop systolic dysfunction, do we improve survival time? This was the exclusion list. So I think the thing to bear in mind is, although it sounds easy to include them in the study, there was lots of other things we ruled out, which made including them more difficult than it sounds, but actually the inclusion criteria are very, very simple.

Results, time to primary endpoint, 718 versus 441 days, and the median survival time all cause mortality was also significantly increased in the Pima Bendin group versus the placebo group. So essentially we're delaying the onset of congestive heart failure, sudden death, by approximately 9 months compared to doing nothing. Treatment also prolongs overall survival time by almost 6 months, when compared to placebo.

So 9 months is a meaningful difference in the course of a disease that lasts 2 to 3 years. You know, increasing the disease course of the pre-symptomatic phase by sort of 30 to 40%, where the animals remain well is certainly, I think, a good thing to try and achieve. Now, the downside of the study was that it was already done in Dobermans, so the question is, is it applicable to other breeds?

So I referred to the authors of the study themselves, and they believe that their results represent grounds to be optimistic that Pinmann would also work in other breeds. And the general consensus amongst cardiologists is that DCM of all breeds, is treated pre-clinically with Pinvendan based on the results of the PTE study. So the updated treatment pathway becomes immabendan in the early stages of the disease, as soon as you've identified systolic dysfunction.

Now, the, those with good echo experience and the, and a cardiologist are gonna be able to identify those dogs with Pymanan at those earliest stages. However, we believe that there is a good benefit at. Any stage pre-clinically.

So, if you, even if you start putting on a bit later on in the disease process before they develop clinical signs, that's likely to have a benefit. And, and realistically, in general practise, I think it's unlikely you're gonna be able to pick up those in the very earliest stages, but you can certainly pick them up in the later preclinical stages of disease. So the new decision pathway based on that data really has to be any concern, even subtle changes, clinical signs, arrhythmia, abnormal pulse, syncope, murmur, anything subtle, we should really, be advocating diagnostics in these cases.

And what you can see now is based on the results of the PTE study, we're now bringing Pymendan treatment right to the earliest stages just after they've developed systolic dysfunction. So they would then get Pymmendan right through until the end stage of their disease. And what that means in terms of survival, well, you can't directly compare these numbers, but it gives you an idea of what we've managed to achieve.

So in the early 90s, dogs were surviving sort of 69 days on freezemide only from the onset of, of congestive heart failure. Once we added in ACE inhibitors, we got some improvements, sort of 130 to 150 days. Once we started adding in Pymendan in congestive heart failure, we made another step forward.

And now we're making another step forward with early treatment of beam. So, you know, I think it's a very encouraging picture of what we've managed to achieve, over the last 20 years in terms of, changing how we medicate this disease to improve survival time. So in terms of the licence, so this is the licence as it is set out, .

What you see is that, unlike in mitral valve disease, where it just talks about diagnostic tests, it focuses on Dobermans here. So strictly speaking, use of it in other breeds is off licence. the other thing to bear in mind is that, it specifically says following echocardiographic diagnosis of cardiac.

Disease. So, I think the pragmatic way of looking at this is, I think it should be offered, Echo should be offered in cases where you speculate cardiomyopathy, but if that's not an option, you may find that, you may have to resort to other tests to try and identify those dogs with cardiogaly. So in terms of identifying the right patients, if you take the start at the top of the funnel, which is all at risk breeds, any that happen to have arrhythmias, .

Should or an abnormal echo have DCM but you really need to identify them with echo. Another way of taking at-risk breeds and trying to sort of narrow down the pool of potentially affected dogs is to consider biomarkers, and then, . Those dogs, elevated biomarkers, you can see, you can consider, doing echocardiography on.

So biomarkers probably have a place in trying to, narrow down the pool of dogs that you might want to echo to see if they're normal or abnormal. So this was an algorithm that was put together by the authors of the Protect study. It's one that was put together by them for Boring Engelheim, so it has that caveat on it, but it was put together by the author of the study.

And their at-risk breeds are dogs over 3 years of age or over 20 kg. Those with abnormal physical examinations or subtle clinical signs, they should be echoed if available. If not, to consider additional tests.

So ECG, chest radiography, NT per BMP. If abnormal, high probability of DCM then they say echo again, because obviously, that's what's on the licence. But I think if, if.

If you'd offered echo to the client and the client said, I can't do it, I don't want to do it, then I think if you'd found significant cardiogalo one of the other tests, I think you'd be quite well within your rights to consider medicating at that point. But I think because the licence says the animal should be echoed, it's probably something that you should at least have a discussion with the client from that perspective. .

So this is that algorithm slightly differently, if you maybe didn't have any access to echo, then at least you would screen with clinical examination findings, er, screen with tests, and then only confirm those that were abnormal, other diagnostic tests with Echo, and that would minimise those, patients that would might, have an echo and be essentially normal. The other thing I think we need to be bear in mind, and this is somewhat the elephant in the room, is that the medicating patients with immibendan for a prolonged periods of time is not cheap. So on the left-hand side is monthly values, and these are probably average values, so your practise may be more or less.

So monthly for those dogs shown, of those kind of weight breeds shown in the pictures, and then annual figures on the right. So your average Great Dane could cost over $20 a year to treat the pinvendan, you. Or Doberman could cost 1500 quid.

So actually, a 200 to 400 scan, pound heart scan, if they don't need medication from the owner's perspective, is a very cost-effective way of identifying whether the patient needs medication or not, because a patient that receives prementum that doesn't need it is going to cost way more to the client than actually undergoing the diagnostics. So in terms of take-home messages to finish up, DCM is almost always progressive. So once you've made a diagnosis, if that patient is still alive and clinically well 3 years later, you've probably made the wrong diagnosis.

And I think the earlier you try to identify these patients, the better your skills have to be, and conversely, if you're trying to pick them up very, very early, unless you do an awful lot of ultrasound, you're probably, your, your misdiagnosis rate will be much higher. The challenge in these cases is identifying the patients that would benefit from early therapy. Conversely, the challenge in mitral valve disease is identifying those that are gonna progress because the vast majority are not going to.

Once you've diagnosed DCM, which is the biggest challenge, as long as that diagnosis. It is right, they will always progress. So I think with DCM it's always worth reassessing, and if 3 years down the line they're still alive, and doing well, then a reassessment of their diagnosis is probably the best way forward.

So apologies for losing you towards the end and I hope that that didn't rush through that last bit too much, but I'm happy to take any questions that might come up. Andrew, it was really just a minor little blip and in, in the big scheme of things that was an absolutely amazing talk and I don't think anybody was at all fazed by it except they, well, to say that they all stayed and hung around and I, I, I'd like to just read you one of the comments that's come through, which is going to epitomise what I think would be a great thank you for you. It comes from David and he says Thank you Andrew for a really interesting, clear and concise webinar.

Usually I get totally bamboozled by the terminology and the therapies in cardiology talks. So quickly lose interest. It's great to have a practical webinar applicable to general practise, perhaps clarifying when to refer.

And I think that sums it up. It's a really brilliant, so that was absolutely fabulous. Couple of questions has come through.

Right in the beginning, you were talking about causes of DCM and you mentioned viruses and Greg's asked which viruses are associated with DCM. So I think the short answer is in humans we don't know. And, .

I would probably have to look up, those viruses in humans, but essentially the classic, so I've got a few friends who are human cardiologists, and I've actually got a colleague who who was unfortunate enough to end up with this condition. And actually what happens in human medicine is there is some viral infection, which is often, you know, relatively short-lived, it might feel like flu-like symptoms, sometimes it's completely asymptomatic. And then, then months down the line, the patient will present with breathlessness.

They go to their GP, they get referred, they end up having low ejection fraction or poor systolic function. They then do myocardial biopsies, and they can see the chronic effects of, of essentially inflammatory response. So I don't, I don't know what their markers of picking up viral, load is, or whether they can identify a virus.

I think in many cases they can't, but there's often in the history, a previous history of a viral infection, which is a kind of inverted commas. I'm doing inverted commas as I say that. So I think it's hard to pick up, and often in human medicine it's picked up after the fact.

But the key difference between human medicine and veterinary medicine in this case is humans do huge numbers of myocardial biopsies, and therefore they are linking echo changes with pathological changes in many of these chronic diseases, and they have a completely different picture then on the underlying cause. We just don't do those, and I don't think we, I don't think we don't do them because they are highly risky. They're done very commonly in humans, in patients with they've had transplants, they'll often do them weekly.

So they're obviously not high risk from that perspective, but I think they're we're gonna have a significant cost implication. And because we don't have the data to say that that would change how we manage these cases, it's very hard, certainly in my setting of working mainly. With private clients to justify getting them to pay for me to do that.

So I think it probably will be something that will come out of the universities, but I think the next step in terms of link, of getting a better idea of aetiology will be doing more myocardial biopsies. Wow, it's just amazing when I think back to that slide that you put on about, you know, how 20 years ago we were just getting 69 days and now we're talking about biopsying the heart. It really is progressing in beautiful leaps and bounds, isn't it?

Yeah, it's, I mean it has it. I mean, it's, that slide, I think, and I will just, I'm just gonna go back to that slide, because that just, when I, if you go back and look at the papers from the sort of early to mid 90s, then, pretty much DCM once it was diagnosed was a, was a death sentence, weeks, some of them, you know, if you look at, so the, the, that 69 days was the median survival time, so. You know, half the dogs would do worse, so some were dying 3 days later, 4 days later.

So, you know, we've had, we've, we've managed to do great things over that time frame, and, and the PTE study is another leap forward. I do wonder though, whether we probably, the next step in the next leap forward we'll probably be getting a better understanding of aetiology. Yeah, and I mean looking at that pre-1996, for those of us that have been around for a long time, DCM was normally a postmortem diagnosis.

Absolutely, absolutely. So yeah, it's come a long way. The other thing to bear in mind is around about 1996, I think was about the time when Peter Dark at Bristol was one of the first people to have a, a, a, an ultrasound in veterinary practise.

So in the early 90s, late 180s, everything was done with radiography. Yeah, yeah. That just leads us beautifully into the next question, which then says, are we being negligent if we don't have ultrasound and if the client can't afford it?

I don't think we're being, I know, I, I, I, I, what, what I think we've got to, well certainly my opinion is that, that we, we, you know. It, the, the way of looking at that question in a slightly different way is, are we gonna withhold treatment if we, if, if for whatever reason the client cannot or won't commit to the, the kind of, the, the definitive diagnostic tests. So I, I, I'm a very, I'm take it very pragmatically.

The licence says we should echo them. So I think we should recommend. Now, that will depend on the level of expertise you have access to.

So the practises I visit, obviously I can echo for them. Some practises have someone who does a lot of echo, so they might be able to pick up earlier. There are lots of cases of DCM out there with very severe changes that haven't developed clinical signs yet, like the ones I showed you in the echoes.

They are ones with a bit of, with a bit of practise, a lot of people will be able to pick those up with very basic. Images. But I don't think, you know, but if a client, if you offer an ultrasound and the client says, no, I'm not interested, and then you do a radiograph and that heart is absolutely massive, then, I would say if the client refuses referral, then I think the only thing you really need to check in that case is that the heart is grossly dilated, there's no pericardial effusion, which is essentially sticking the probe on the skin.

So any ultrasound. Scanner will do that. And then actually pragmatically saying, well, I think this is most consistent with delayed cardiopathy.

The client has refused a definitive diagnostic test. Therefore, am I gonna withhold potentially life changing medication from that case because the client has said no, I think there is always a school of thought for for weighing up the risk and saying, you know what, I'm gonna treat that patient. The other thing is of course to keep in mind, Andrew, is that if a client has said no because they can't afford it, it's unlikely they're gonna be able to afford extended treatment anyway.

Absolutely, absolutely. So I think if cost is the absolute issue, then we probably have a problem, but I think that in some client, I, I found that trying to convince the client to do diagnostic tests when the animal from their perception as well, is much more difficult than when they have a problem. And the problem we have with DCM is the majority of dogs that are gonna benefit most from treatment are gonna be asymptomatic in the eyes of the owners.

So there is a, there is a there is a discussion we have to have with the owners saying we need to look now, even though you think your dog is completely normal. And the reason why we need to look now is because if we find. That they do have DCM we can make a meaningful intervention which has a meaningful outcome for the client and for the owner.

And I think if you frame it in those terms, bearing in mind that the diagnostics are usually way cheaper than a year of medication, that actually we probably just need to focus on doing the diagnostics first. And not all the owners will say yes, . But I think if we frame it that way, we're probably gonna end up being able to look for more.

But I absolutely don't think, if the client, if the client, if the client says no to referral, even if they've got money, that ultimately is their prerogative, and therefore, I would then move to the next step, which is, I can't necessarily make a definitive diagnosis, but I can probably get, I can see whether they're grossly abnormal by. Putting my ultrasound probe on and if I'm not sure, I can save some images and send it to a friendly card register and see if they will make the judgement for me, if it's obvious. Or I will do some diagnostic tests that identify cardiomegaly, and if both the radiograph and the NTO BMP are abnormal and the client has refused Echo, but they still have money, I would probably treat that dog in any case.

And I think the big thing there is, is to just document your conversations because the minute you start going off licence and you can document and show that you have discussed it, I think you're covered. And there's a couple of questions coming in about insurance and that sort of thing. And I think that's the big thing there as well is, is, you know, document what you've done and then check with the insurance company because each one is gonna be an individual like our, our clients always are.

Yeah, absolutely. I've never, I've never had any issues with insurance so far. I think the insurers tend to .

You know, that they, they aren't, you know, it's a, it's a, it's now, it's not a, it's not a, contentious issue treating them early, in actual, actual fact we've streamlined how we manage them, so. You know, I remember pre-protect study days we were doing variable other things, adding in ACE inhibitors early, adding in other, other, other, medications early. Now, no one's proven that other medications aren't also beneficial in these early stages, but at the moment, we've got a clear intervention point for one medication and actually none for any others in the earlier stages.

So, there are probably quite a few dogs on there, on polypharmacy in the early stages, so if this streamlines them onto. Uni pharmacy, I, you know, it may not necessarily change the cost profile to the, to the insurance companies necessarily that much, but I've never had any issues with insurance companies. I think they understand that this is a very clear cut.

Treatment choice. Yeah. Interesting question that's come through that says, would you use permabendin dose at the recommended 2.5 milligramme per kilogramme BID from the word go?

So my advice is, so I always try and use the study dose. So the studies, the studies, all the studies that have been done in Pimmaendan, so the, The quest study, the Protect study, the EPI study have all been done with 0.25 milligrammes per kilogramme peros twice daily, OK.

So it's the top of the licence dose range. So I will usually try and get the dogs as closest to that range as I can. I try not to go over the 0.3, which is the top of the dose range twice a day, but I try to get as close to the 0.25 as I can.

And the reason I do that is because strictly speaking, If you're gonna apply the results of a clinical study to your clinical practise, then you should closely try and mimic the population of mimic the what the study population was. So we know this study was only Dobermans, but all of the authors agreed that it that it, given the similarities in, in the forms of DCM that there is a remit for using it in. All large breed dogs, but I think the key thing is one thing we can easily, standardise is that the study dose is 0.25 metres per kid twice a day, so we should use that dose.

Excellent. There's a lot of other comments coming through here saying things like brilliant webinar, useful webinar, brilliant useful webinar. Thank you so very much.

Andrew, I think everybody agrees that this has been an amazing webinar. And the fact that all the attendees are still attending at this stage, just bears witness to that. So.

It's my privilege to be able to thank you and to say I hope we see you back on a future webinar. Well, it's an absolute pleasure and thank you everyone as I say, for taking time out of what was a lovely evening to, listen to, my talk on Diarinopathy. I really hope it helps you identify more dogs with DCM because it's relatively rare that we come, come across a treatment option that makes such a meaningful difference for which there is strong evidence.

Excellent. Andrew, thank you again and folks, thank you for attending tonight. Anthony in the background, thanks for getting Andrew back online with us again.

And until the next webinar, it's goodnight from me. Good night.