Hello and welcome to this lecture, brought to you by the webinar vet on canine and feline, pulmonary hypertension, more common than you may think. Pulmonary hypertension can be defined as increased pressure within the pulmonary vasculature, and we'll get into that in a bit more detail a little bit later on, but it essentially itself is a complication of numerous other conditions rather than itself being its own disease entity. And the normal mean pulmonary arterial pressure should be less than 25 millimetres of mercury at rest, and with pulmonary hypertension we have pressures increasing above this, although in some patients with pulmonary hypertension, their pulmonary pressures can be normal at rest in early disease.
So why are we talking about this? Why do we think it's worth knowing more about? And for me, the reason is that I think pulmonary hypertension causes significant morbidity in many of our patients, and obviously most commonly in those with pulmonary disease.
Developing pulmonary hypertension secondary to that, but there's quite a few of the disease states as well, which can lead to pulmonary hypertension. So it certainly causes quite a bit of patients suffering, and we need to be able to really detect it, you know, diagnose it and treat it effectively to improve outcome in our patients. And this lecture is definitely aimed.
You guys that are in primary care practise, and I think the reason why I really wanted to do this lecture is because I'm not sure how regularly pulmonary hypertension is identified in primary care practise, or at least how regularly it's screened for. As we'll get on to it a bit later on to sort of diagnose pulmonary hypertension, you certainly need an echocardiogram, you know, and diagnosing pulmonary hypertension or an echocardiogram is at least an intermediate sort of level skill. So whilst it's not something that you guys might all be comfortable doing yourselves in primary care practise, I just think it's really important for you to be aware of which patients could have pulmonary hypertension and how to screen those patients for it.
So we'll go through pulmonary hypertension in the context of really what to expect in a primary care setting. And I just also wanted to make reference to this paper here. So this is one of the ACVIM consensus statements.
They are open access, so free to view online through the Journal of Veterinary Internal Medicine, and in 2020 they published the consensus statement on the diagnosis and treatment of pulmonary hypertension in dogs. It's a really, really good read, and I've taken a couple of sort of snippets of information and the diagram from that paper itself. So pulmonary hypertension is most frequently diagnosed in dogs, and we're really going to concentrate on that species for this talk.
It's much less common in cats, and when we do see it in cats, it's often secondary to left-sided congestive heart failure. And the prognosis in these patients can really vary dramatically between individuals, with some patients succumbing within days to their disease and pulmonary hypertension despite treatment and having, you know, a grave prognosis, whereas other patients potentially. May have a completely reversible, disease that's causing their pulmonary hypertension, and the accurate diagnosis and treatment of that underlying disease, could confer an excellent long-term outlook, in those patients.
To understand more about pulmonary hypertension, we need an understanding of the anatomy physiology initially, so we can understand how and why things go wrong. And so the lungs are a unique organ that they have double circulatory system. Firstly, they have the pulmonary circulatory system, which we can see on this diagram here.
Where we have deoxygenated blood from the body entering the right side of the heart, going through the pulmonary artery to the lungs, becoming oxygenated, and then through the pulmonary vein to the left side of the heart and out to the systemic circulatory system. But the lungs themselves are supplied with oxygenated blood through the bronchial circulatory system, so we don't need to worry too much about that regarding the context of pulmonary hypertension. Instead we're going to focus on on the pulmonary circulatory system.
Now the pulmonary circulatory system is highly compliant. Which is really useful because it allows, increases in cardiac output, from the right side of the heart to the lungs, without increasing pulmonary vascular resistance. So that's really important so that when we're in, you know, states where, we have increased cardiac output because of exercise, for instance.
We're not going to significantly increase the pulmonary pressures because the compliance of those vessels means that there isn't a significant increase in pulmonary vascular resistance as the cardiac output increases. So that's one thing that's important to be aware of. And we also need to understand this idea of ventilation and perfusion.
So when you have an area of the lungs that's not well ventilated, for instance, in a lung lobe that has severe pneumonia, there is local pulmonary vasoconstriction to allow blood to be diverted away from those poorly ventilated areas of the lungs to the better ventilated areas of the lungs to help with oxygen saturation of the blood. So that makes sense, and it's certainly beneficial in the acute situation. However, chronically, this can be deleterious, as that chronic vasoconstriction, along with some of the other things that we'll talk about in just a second.
And will increase pulmonary vascular resistance. OK. The more blood vessels we have that are vasoconstricted, the higher the resistance of flow, you know, through those vessels is.
So that chronically increased pulmonary vascular resistance can lead to pulmonary hypertension. And also we have to bear in mind that chronic hypoxemia as well, within the blood causes itself vascular remodelling, and that vascular remodelling. Essentially reduces compliance of these vessels and leads narrows these vessels and precipitates sustained elevation in pulmonary vascular resistance and therefore worsens any elevations in the pulmonary pressures.
So we've talked about how changes within the lungs and particularly the blood vessels within the lungs will increase. The pressure within the pulmonary circulatory system. Now that pressure within the pulmonary circulatory system is, .
Referred to really as the afterload on the right ventricle. So the afterload can be thought of as the pressure in the system that a chamber is having to pump blood into. So the right ventricle pumps blood into the pulmonary vasculature.
If the pressure is increased there, then the right ventricle needs to generate more pressure to get the blood to move into that system, OK. And this is referred to as increased after load on the right ventricle, and when this occurs, there is compensatory hypertrophy of the right ventricle. To allow the ventricle to be able to contract with more force, essentially, to allow an increased pressure, to be able to, to move the blood from the right ventricle into the pulmonary circulatory system.
And we can see on this nice image here from the textbook of cardiovascular medicine by Claudio Busadorri that this right ventricular hypertrophy can be really quite pronounced. So on the left side here we've got a normal heart. This is the right ventricular outflow tract here and this is the free wall of the right ventricle, OK?
And we compare that now to a patient here that had chronic pulmonary hypertension. In which you can appreciate really pronounced concentric hypertrophy of that freewall there. Now this concentric hypertrophy will happen initially, but over time as the myocardium starts to fail.
We will start to, develop eccentric hypertrophy as well. So the right ventricle will begin to, dilate, and we refer to this as an afterload, mismatch. And once we then have elevated right-sided pressures, right-sided cardiogaly, this is when pulmonary hypertension can ultimately lead to signs of right-sided congestive heart failure.
So we'll get to those in just a couple more minutes. So this diagram here is taken from the ACVIM consensus statement on pulmonary hypertension, and I think it's a really nice way of thinking about the types of changes that can lead to pulmonary hypertension in our patients. So firstly, we have increased pulmonary blood flow.
So this is seen in patients typically with congenital left to right shunts of the heart, the classic example being a PDA in which we have significantly increased volumes of blood moving through the pulmonary vasculature, therefore increasing pulmonary pressures. We then have the patients with the increased pulmonary vascular resistance that we've talked about quite a lot. And these patients normally develop the pulmonary vascular resistance, because of chronic hypoxemia.
And primary diseases of the lungs, and the pulmonary vasculature itself, and the resistance can go up due to many of these, mechanisms, including pulmonary endothelial dysfunction, vascular remodelling, perivascular inflammation, luminal obstruction, increased blood viscosity, which may be seen with, you know, hyper viscosity syndrome, arterial wall stiffness, and lung parentchimal destruction. We then have the patients that have increased pulmonary venous pressure. So these are referred to as patients with post-capillary disease, and these are patients who essentially have left-sided heart disease.
So when we're thinking about that diagram of the pulmonary artery going to the lungs and then, the pulmonary vein leaving the lungs and going to the left side of the heart. If we have significantly increased left sided filling pressures because of left-sided heart disease such as myxomatous mitral valve disease, that will confer increased pressure into the pulmonary vein and ultimately lead to vascular remodelling within the capillary bed within the lungs, and that will lead to increased pulmonary pressures as well. Now we're going to move on to the clinical signs that can suggest a patient may have pulmonary hypertension and start to ring the alarm bells that that that patient might need screening for it.
So, a lot of the symptoms of pulmonary hypertension, you know, can be the same as those for other primary heart and lung diseases. So they're not that specific. Which is why I think often pulmonary hypertension, you know, can be overlooked as a differential in patients.
But nonetheless, these are things to sort of be aware of. So clinical signs that are strongly suggestive of pulmonary hypertension includes syncope, which most commonly occurs during exercise or exertion. Respiratory distress at rest, very concerning obviously for the patient.
Activity or exercise that precipitates in respiratory distress and signs as well of right-sided congestive heart failure. So those are of course, ascites. Pleural effusion leading to, a restrictive breathing pattern and muffled heart and lung sounds, and patients as well who have jugular distention, jugular pulsation, and or a positive about a jugular reflux.
Symptoms that can be possibly suggestive of pulmonary hypertension, a tip near at rest, increased respiratory effort at rest rather than overt distress, prolonged post-exercise tachypnea, and cyanos or pale mucous membranes. OK, so now I'm going to show you a video of a patient with pulmonary hypertension and essentially we're performing a hepatojugular reflux. So, I'm filming and looking at the patient's jugular vein, and my colleague is squeezing the cranial abdomen in the area of the liver, and you'll see that as we do that, the jugular vein raises, and so now.
Yeah, you know. And then release it? Now, now, now it's perfect.
Pressing there and then. Press Release. Come OK, so that's a really nice test that you can do very easily to help screen for evidence of, you know, right-sided congestive heart failure.
It's really nice when, when you see it, you know, as demonstrated by our Italian intern there. OK, so we've got a patient that we think could have pulmonary hypertension. How are we going to go about diagnosing them?
Well, ultimately in humans, the gold standard is direct catheterization of the pulmonary artery and measuring the direct pressure, and we don't do that in animals. So instead we rely on echocardiographic diagnosis, where we sort of look for the changes within the heart that can be suggestive of pulmonary hypertension. And we can indirectly, estimate the pulmonary pressure by making some, measurements on the echocardiogram.
So the important thing to remember is that this will give us a probable diagnosis of pulmonary hypertension rather than a definitive diagnosis, and the ACVIM consensus statement recommends we sort of use that terminology. So we sort of say, you know, this patient has a high probability of pulmonary hypertension rather than they have severe pulmonary hypertension. So the things that we're going to look for are evidence of right atrial and right ventricular cardiomegaly.
So I'll show you some nice examples of some sin loops in just a second. We're also going to look for dilation of the pulmonary artery, OK, and often that's by comparing the size of the pulmonary artery to the aorta. When we have increased filling pressures within the right side of the heart.
If they become higher than the filling pressures in the left side, which they shouldn't be, then we'll start to see flattening of the interventricular septum, because of the increased pressures on the right side of the heart, pushing the septum over to the left. And one of the things we're really gonna keep an eye out for is, evidence of tricuspid regurgitation. So a lot of patients, really the vast majority of patients who have pulmonary hypertension will develop tricuspid valve regurgitation.
So this is one of the things that you need to look for in your physical examination, OK? So you're going to Aus will take the right side of the chest over the area of the tricuspid valve for any evidence of a systolic heart murmur. It really doesn't matter what the grade of that murmur is, any murmur in that area in a patient that could have pulmonary hypertension should be considered significant.
And when we echo these patients, we're able to measure the peak velocity of the flow of that tricuspid regurgitation, and we can actually use that to calculate the mean pulmonary arterial pressure to give us a bit of an idea about, you know, how sort of severe this patient's pulmonary hypertension might be. And we can also look for enlargement of the caudal vena cava as well. So just finishing up a little bit about the tricuspid valve regurgitation.
When we do detect tricuspid valve regurgitation, the velocity of that flow should really always be below 2.8 metres per second if we have normal pulmonary pressures. However, when we have velocity of flow above 2.8 metres per second, as you can see in this patient, it's somewhere in the order of 4 metres per second.
That is abnormal. And when we detect this increased velocity flow in tricuspid regurge, it tells us that there is either pulmonary hypertension or pulmonic stenosis, so we have to exclude pulmonic stenosis on the echocardiogram. Before we can sort of, you know, suggest pulmonary hypertension, but that should be, somewhat straightforward.
And what we can do with this, maximum velocity is we can plug it into the simplified, Bernoulli equation. And that will allow us to be able to actually calculate an estimated pulmonary mean pressure from the velocity of this regurge using 4 times the velocity squared. So I'll show you an example of that in just a second because you're probably thinking this is very confusing and I'm not sure if I'm following, but trust me, you will.
So here's an echocardiogram of a patient with pulmonary hypertension now. Here we have the left atrium of the heart. Here we have the left ventricle.
The right ventricle is here, and here is the right atrium. There's the tricuspid valve, and here is the mitral. Now what you can appreciate is that the right atrium is significantly bigger than the left, and that should never be the case.
We also have a massively enlarged right ventricle. The right ventricle is almost twice the size of the left, and really that should be the other way around. The left ventricle should be 2 to 3 times the size of the right.
We also note that the interventricular septum here looks as if it's bowing towards the left side of the heart, and due to the elevated right-sided pressures. And the left side of the heart as well, the muscle looks sort of thickened and it doesn't look like there's a lot of blood in this lumen here. And that's because the left ventricle is very much underfilled.
As we said earlier, when the pulmonary pressures are very high, it increases the afterload on the right ventricle, and that will reduce the cardiac output from the right ventricle. So we get less blood entering the pulmonary vascular system and then returning to the left side of the heart. So we get underfilled left ventricle and the left ventricular cardiac output will then be reduced.
And this view, in case you're wondering, is the right power sternal long axis for chamber view. And on this next slide, I'm going to show you the right parasternal short axis view at the level of the mitral valve. So this is the heart and transverse section, and this is the left ventricle here.
So the left ventricle should be 2 to 3 times the size of the right, whereas in this patient this huge right ventricle around it is about 2 to 3 times the size of the left. So that's very abnormal. We also know that the left ventricle itself should be very round, very spherical in its shape.
And instead, what we can start to appreciate is this D-shaped appearance where the interventricular septum here looks really quite flat. Because Of the increased pressures in the right ventricle pushing that wall towards the left, and whereas the free wall looks much more rounded, so instead of having an overall round shape to the left ventricle, we get this sort of D shaped appearance, and this is referred to as flattening of the interventricular septum. So those two things are really quite obvious, honestly characteristic changes of pulmonary hypertension.
They're not specific to just pulmonary hypertension, don't get me wrong. But with some basic, to intermediate echocardiographic sort of skills, you know, you can rule out the other differentials for that right sided cardio megaly and increased filling pressures. You know, and, and start to really increase the index suspicion that patient has got pulmonary hypertension.
And This image here just shows the main pulmonary artery here and the right ventricular outflow tract, and this main pulmonary artery splits them into the right and left pulmonary arteries. And this is the aorta next to it and essentially this pulmonary artery is enlarged, so it should be about 1.1 to 1 times the size of the aorta, and in this patient we've got 1.34 centimetres to 2.18 centimetres, so it's definitely dilated there.
This is then an example where we are measuring the peak flow velocity of tricuspid valve regurgitation using spectral Doppler. So these are the envelopes of the tricuspid regurge, and when we measure the peak velocity here. And we can plug that into the modified Bernoulli equation.
So we do 5.65 metres per second squared times 4, and that comes to about 128 millimetres of mercury. So this is a patient with severe pulmonary hypertension, and if you remember at the beginning of the lecture I said normal pulmonary pressures are less than 25 millimetres of mercury.
This patient has obviously got a serious problem as their pressure is nearly 130. And we used to before the ACVIM consensus statement, sort of grade patients' pulmonary hypertension as mild if it was 25 to 50, moderate if it was 50 to 80, and severe if it was above 80 millimetres of mercury. We've sort of moved away from that now because what we find is that regardless of how high the pulmonary pressure is.
It, it doesn't really correlate in every patient with severity of clinical signs. So we can have patients with really severe, pulmonary pressures, but actually the clinical signs aren't too bad. Does that mean they have severe disease?
And conversely, we may have patients who have Only mild to modest increases in the pulmonary pressure, but actually you're suffering, you know, quite profound clinical signs. So we've kind of moved away from that system, but, you know, if you were, thinking about over 80s being severe, this patient certainly has, one heck of a problem. So that's how we would look at diagnosing pulmonary hypertension.
Echocardiographically. So now we need to think about the types of diseases that can cause pulmonary hypertension. So we've said that it's a consequence of other diseases.
So when we know a patient's got pulmonary hypertension, we then start to look at that patient and try and figure out what is causing it, because ultimately the treatment of the underlying cause is the best way to help treat their pulmonary hypertension. So the ACVIM consensus statement grouped the causes of pulmonary hypertension into 6 different types. And they are as follows.
Type 1 is pulmonary arterial hypertension, so go through these in a bit more detail in a second. Type 2 is pulmonary hypertension, due to left sided heart disease. Type 3 is respiratory disease, chronic hypoxemia, or both.
4 pulmonary thromboemboli, 5, parasitic disease, and 6 are those that have multifactorial mechanisms, so several of the other types all coming together, or perhaps unclear, mechanisms of their pulmonary hypertension. So just starting with type one, so these are the patients that can have pulmonary pressures being elevated because of congenital left to right shunts. So the good example being the PDA where we have a connection, you know, between the aorta and the pulmonary artery.
So as oxygenated blood leaves the left side of the heart, and instead of going through the circulatory system. It's sent back, into the pulmonary artery. And round through the lungs once more back to the left side of the heart, and you know, and this causes a big increase in the pulmonary flow and that leads to increased.
Pressures, as well as chronically, we get, remodelling, of the pulmonary arteries in these patients as well, which will worsen, the pulmonary hypertension. Now, that obviously, leads to right-sided cardiogaly with, with pulmonary hypertension, but we also have really quite profound left-sided cardiogaly in those patients. Because of the left to right, shunting causes really, volume overload of the left side of the heart.
Now, one thing to bear in mind in those patients is that as pulmonary, pressures start to increase. Over time as their disease gets worse, what can happen eventually is something called Eisenmannge syndrome, where the pressures in the pulmonary artery become so high, they are higher than those in the aorta. Now, that's not normal at all because, you know, we've said already pulmonary arterial pressure should be less than 25 millimetres of mercury, .
Pulmonary, sorry, the pressures in the aorta or the systemic circulatory system, you know, should sort of be in the order of about 120 millimetres of mercury. So when we do get these massive increases in pulmonary pressure, it can actually start to mean that the blood instead of moving from the higher pressure left side of the heart to the lower pressure right side, that shouldn't flow can reverse, and we start to see deoxygenating blood. Entering the right side of the heart and then it shoots through the shunt from the higher pressure pulmonary artery to now the lower pressure aorta bypassing the lungs and this delivers deoxygenated blood then to the circulatory system, you know, and can lead to some pretty severe complications including hind limb cyanosis in individuals.
And erythrocytosis, as well as a response to the, the chronic hypoxemia that these patients suffer. Other than congenital heart disease, we also have idiopathic pulmonary, arterial hypertension. So this is something that's really made as a diagnosis of exclusion, if we can rule out all the other causes of pulmonary hypertension.
And that's all that we're left with, and that's the diagnosis. But we also have much less sort of common and tricky to diagnose necrotizing vasculitis slash arteritis, and pulmonary veal occlusive disease and or pulmonary capillary hemangiomatosis. So if we have a patient that we think has got type one disease because I guess maybe we've auscultated their chest and we can hear a continuous, you know, heart murmur that's suggestive of left to right shunting, then these patients are really, you know, best undergoing full cardiac workup.
And because of their complex nature of some of these congenital heart diseases and the possibility of interventional therapy, you know, such as ductal occlusion of the PDA, these patients really are then best referred, you know, to a specialist cardiologist for full workup as needed. So type 2 patients, these are those patients that have elevated left-sided filling pressures because of advanced left-sided heart disease. And the vast majority of the time that's acquired heart disease, so mixed is mitral valve disease in dogs, dilated cardiomyopathy in dogs, cardiomyopathy in cats.
And this is certainly the most common form of pulmonary hypertension that we diagnose in dogs. However, it's not often that clinically relevant in these patients because their pulmonary hypertension seems to be somewhat more mild, certainly when compared to the clinical significance of their left-sided heart disease. So as we said earlier, these patients have post-capillary pulmonary hypertension, and this initially develops passively because we have increased left atrial pressures, which increases the pressures in the pulmonary vein and therefore increases pressures in the pulmonary artery.
But in the chronic disease state, we also get, what we call combined. Pulmonary hypertension in these patients, not only because of the passive increase in pressure, because of the, left atrial pressures being high, but also chronic vascular remodelling as well, within the lungs increases pulmonary vascular resistance as well. So these patients, .
Are often coming in because of their primary heart disease, quite honestly, and they're often undergoing echocardiography for that reason. And it's often then that we sort of stumble across the fact that they've got pulmonary hypertension. And we sort of note it and you know, make recommendations based on the severity of the pulmonary hypertension, left sided heart disease, and we'll monitor appropriately.
But these patients often don't present because of their pulmonary hypertension, and we then realise they've got left sided heart disease. It's more, you know, the other way round. And these patients also benefit from thoracic radiography to understand more about their left sided heart disease.
Blood pressure measurement is really important in heart disease patients, so we can help screen for pulmonary. Not pulmonary, sorry to say that, systemic hypertension, which can actually increase the aft load on the left side of the heart and, you know, necessitate, anti-hypertensive medications. And these patients often, benefit from ECGs, as well.
So here's an echocardiogram of a patient with advanced left-sided heart disease. So this was a dog with myxomatous mitral valve disease, so we could see some pretty nodular. A thickened mitral leaflets here.
This patient, we've got really quite profound left atrial and left ventricular cardiomegaly, and there's also some increased sphericity of this left ventricle which you know can occur in the more advanced stages of mitral valve disease when the left ventricle eccentrically dilates. But this patient had pulmonary hypertension as well. But note how different the echo looks compared to the last patient that we were looking at who just had, you know, right-sided heart disease.
So even though this patient's right atrium is not bigger than their left and their right ventricle is not bigger than their left, they are still enlarged, OK, but this patient primarily has left sided heart disease and the pulmonary hypertension has developed secondarily to that. And here we have an estimation of the left atrial size, so the LAAO in this patient was 2.66, so really, you know, markedly enlarged, and the patient was in left-sided congestive heart failure.
We then have a still image for the left apical view where we have the left atrium here, left ventricle here, right ventricle right atrium, and this is colour flow of our tricuspid valve regurgitation, and then we measured the velocity of this using spectral Doppler. So here we have the spectral Doppler of the tricuspid valve regurgitation, from the left apical view. And these are the envelopes of tricuspid valve regurge.
There's quite a bit of variation right in the velocity of flow here. And if you look as well at the sort of timings, there is an irregularity because this patient was in atrial fibrillation and as a result of that tacky arrhythmia, you get quite a lot of variation. And how much, blood is within, the heart, when it contracts, because the diastolic filling period is very irregular, because it's an irregular heart rhythm, but it's also quite short because it's a tacky arrhythmia.
But nonetheless, we measured the peak velocity here, 3.77 metres per second. So, we use a cutoff of 3.4 metres per second as being significantly increased and suggestive of pulmonary hypertension.
So that's when we calculated the mean pulmonary pressure using the simplified Bernoulli equation gave us a pulmonary pressure of about 57 millimetres of mercury. So certainly increased but not through the roof, and that's often the case with these patients with type 2 disease, secretary to left sided heart disease, that the pulmonary hypertension is often there, but it's often not that clinically significant. It can, however, if, if, progressive, you know, leads to right-sided heart failure, in patients who started originally with left-sided heart disease, however, such as, you know, mitral valve disease.
Type 3 pulmonary hypertension. So this is a very common cause for pulmonary hypertension, and these are patients that have chronic respiratory, well they can be acute, acute or chronic respiratory diseases and hypoxia. And we talked about the pathophysiology of this earlier on, so think about any, you know, airway, lung disease, potentially leading to pulmonary hypertension.
But there are some classic examples that we think of, and I think idiopathic pulmonary interstitial fibrosis that we often see in West Highland white terriers, you know, is a great example of one. And if I ever diagnose a Westie, you know, with pulmonary fibrosis, if they're showing any of those symptoms that are potentially suggestive of pulmonary hypertension, I'm always going to want to do an echocardiogram, you know, in those patients. But other diseases as well include those, patients who have, say chronic bronchitis with bronchoalacia.
So bronomalacia is the same disease process as tracheomalacia, which you can see in this patient here, tracheal collapse, but it affects the bronchi, as we can see in this patient here. We've got significant collapse of that left main stem bronchus there. So you know, other diseases as well, even brachycephalic obstructive airway syndrome, you know, has been associated with pulmonary hypertension.
So When I, have a patient who's got chronic lung, upper airway disease, you know, if they're showing any of those symptoms of pulmonary hypertension, I'm going to screen them for it. Or if they are really not responding to treatment, as I would expect. You know, it's just one of the things that I think we have to look for to say, well, you know, I've diagnosed this dog with such a condition.
It's really not responding to that treatment, you know, either we've got the diagnosis wrong, which, you know, hopefully isn't the case, or there is some sort of complicating factor here that we're not, you know, aware of, and that may well may may well be pulmonary hypertension, so it can be worth screening for in those guys. And when we're working at patients with type 3 disease, they often come in, you know, with signs of primary sort of respiratory tract disease, and it's often, as we're investigating that we start to have an increased suspicion of pulmonary hypertension and then decide to, you know, to do an echocardiogram. But when we're working up these patients, they're often coming in having blood work, you know, to check major organ health.
Check for markers, you know, of inflammation like neutrophillias or hyperglobulin anaemia, checking for any evidence of parasitic or hypersensitivity lung diseases, looking at the inophil counts. We may use some blood work to screen for. Infectious diseases, within the lungs, like angio detect the Andrewstrong's zorum, although that kind of falls into, the 5th type of patients that we'll get to in a second.
And ultimately these guys will undergo imaging which will either be CT scans of the thorax, you know, or radiography. To sort of document their primary, respiratory tract disease. But also, you know, CT and radiography can help increase the suspicion of pulmonary hypertension.
So here we have a dog that underwent CT, the thorax, that also had pulmonary hypertension, and we can see a really dilated main pulmonary artery here when compared to the aorta and the right, you know, and left pulmonary arteries here are dilated, . A lot of these patients as well will undergo bronchoscopy, in order to get a definitive, diagnosis, in combination with broncho-alveolar lavage. And I thought I'd just show you a couple of radiographs.
So this is a patient who has got pulmonary hypertension, and they've got pulmonary hypertension secondary to chronic airway disease. So this patient had a chronic cough but also had evidence of exertional syncope as well. And on these radiographs in these lung fields here, we can see a broncho an interstitial pulmonary pattern suggestive of significant airway disease there.
The heart itself looks largely normal, although there is some dilation of the caudal vena cava here. And this patient, you know, had orthogonal views taken and, then went on to to bronchoscopy. But on the DV view, what you can do is obviously have a look at the pulmonary rankima, have a look at the left and right sides of the heart, but you can actually have a look as well for the pulmonary artery which can form a bulge of the heart at the sort of 1 to 2 o'clock region.
So at 12 to 1 o'clock we have like the aorta. 1 to 2, the pulmonary artery, yeah, and 2 to 3 you can get left aricular appendage if that's enlarged. So this patient did have a bit of a bulge here.
We can also look at the pulmonary lobar vessels as well. So here we have an airway, OK, you can see that because it's more radiolucent in the structures around it. And on this side of the airway we have the pulmonary lobar artery.
And here the vein. So what we can see in some individuals is that this pulmonary lobar artery can be dilated, you know, when compared to the pulmonary lobar vein, and that itself could be radiographically suggestive of pulmonary hypertension. So type 4 patients, are those that have .
Thrombi, within the lungs, so vascular occlusion. And these patients can develop blood clots for a variety of reasons. But I think probably the most common one.
Is that they have a hypercoagulable disease state, a thrombus forms somewhere in the body and embolizes to the lungs causing an obstruction. And there are certain sort of hypercoagulable disease states that we're all aware of, and, you know, and often prophylactically treat to help reduce the risk of thromboembolic disease, and some good examples being immune mediated hemolytic anaemia, . Protein losing, nephropathies, protein losing enteropathies, canine hypergena corticism, you know, all of these diseases increase coagulability and increase the risk of thrombobolic disease.
But there are other. You know, reasons why we can become more likely to develop a thrombus. And if we think about Viau's triad, they, the three, you know, factors include hypercoagulability, which we've mentioned, endothelial injury.
So primary disease processes that damage the blood vessels in an area will increase the risk of thrombus formation in those areas. But also stasis of blood flow, which is something that we often really appreciate in our cats who develop, aortic thromboembolisms because of stagnant blood flow in their massively dilated left atria and aricular appendages. So these patients are really quite tricky, honestly, to diagnose, and normally these patients, we see an animal because of respiratory distress.
We document pulmonary hypertension, and then we sort of investigate that, you know, one of the things that we look for is evidence of thromboembolic disease. And so we will do some blood work, . To look really for any evidence of diseases that can be, you know, associated with robolic disease.
So as I've said, IMHA protein losing nephropathies, canine Cushing's disease, but we can also do testing as well to see if the patient appears to have had, you know, a blood clot looking at things like D dimers, you know, and FDPs. We can image these individuals and you know, sometimes that can be rewarding. Other times imaging can be very unremarkable in patients even with severe thromboembolic disease.
And when we are looking at imaging these patients, if possible, advanced imaging with CT angiography. It's preferable, to be able to get really nice arterial phases within the lungs, which with contrast enhancement allows us to identify, blood clots much more easily, than we can on things like thoracic radiographs. So I wanted to show you a patient that has, you know, really, really nice example of type 4 disease, and this was a cat who presented with a pneumonia.
So there's multifocal changes, you know, within the lungs here and on the CT scan that was really evident. This patient obviously underwent bronchoscopy and bronchialy lavage. But also noted on the CT scan was a really big thrombus in the right pulmonary artery.
So this is the right pulmonary artery here, and the pulmonary artery should be filled with white contrast enhancing fluid. And which was injected IV, but instead we have this big dark thrombus all the way along here, really massive thrombus and transverse section you can see it here very much occluding that artery, and there is no contrast flowing through it. So this thrombus we believe formed in situ.
So rather than it embolizing from somewhere else in the body and getting stuck in the lungs, it looks like this severe inflammation in the right side of the lungs. Causing the vascular remodelling, vasoconstriction, activation of inflammatory cytokines, . For a thrombus to form in situ within the lungs.
And we did perform echocardiography in this cat, and you know this is a half speed echocardiogram, but the changes that we saw were not dissimilar from those that you'd see a dog with pulmonary hypertension. So the right atrium here is about the same size, if not slightly bigger than the left. So there's some right atrial cardiogaly.
The right ventricle here is not quite as big as the left, but certainly bigger than it should be. So this is definitely evidence. You know, of a right sided Cardi Megley in this cat.
We then looked at a short axis view where we have the left ventricle just here. The right ventricle here looks a lot bigger than it should be. And the interventricular septum here looks flattened once more, instead of the left ventricle being a nice rounded shape.
We then had a look at the pulmonary artery. So here's the aorta in short axis. We've got the pulmonary artery, the main pulmonary artery coming down here.
We got the left pulmonary artery here, and then this is the right pulmonary artery with this large echogenic structure sat within it. OK. So this structure here, and this was the thrombus.
We then applied our colour flow. And as you can see, we've got colour flow here moving down through the left pulmonary artery that is of course patent, whereas we don't have any colour flow moving through this region here where we have the thrombus, you know, blocking literally you know, half of the lungs from receiving blood from the heart. So obviously that's going to significantly.
Increase, the, pulmonary pressure because of that, obstruction in that area, and further worsen this patient's, hypoxemia. Due to a lack of blood flow to the right side of the lungs. Type 5, are the patients that have pulmonary hypertension, secondary to, parasitism.
In the UK Androstroospizorum is by far the most common culprit, although don't forget that we do have other lung worm as well as Laros' Lari and crenoso of vulpes, but angiostrospizorum is not uncommonly associated with pulmonary hypertension, particularly in its severe and more chronic forms, and, . This is something that we're going to definitely screen our patients for with a combination of Snap testing. Now do bear in mind that the angio detect, which is available for an IDEX, you know, has a reasonable sensitivity and specificity, but it's not 100%.
And essentially if you have a positive angiodetect test because of the, you know, honestly pretty high specificity, it's likely a true positive. That patient likely has lung worm. You know, we might not need too much in the way of further evaluation.
However, if you have a negative lung worm test, do not rule out lung worm in these patients. Keep it on the list of differentials, and instead we're going to perform more sensitive testing for these individuals, and the gold standard of which should be considered PCR on broncho alveolar lavage samples. And if we have a patient that's had a travel history to an area of the world in which heartworm is endemic, then we're going to want to screen these patients for diaphylaria, as that as well can lead to significant pulmonary hypertension.
And of course the treatment of diaphylaria, you know, is very, very different from that of other sort of pulmonary parasites. So these patients are often diagnosed on a combination of echocardiography. Imaging, so radiographs and CT scan to look for changes that are, you know, compatible with either of these two sort of diseases, and then ultimately specific parasite testing, you know, as I've already, mentioned.
. So, those are the types of pulmonary hypertension, and we're now just gonna finally wrap up on treatment. And as I said earlier. The really best way to treat pulmonary hypertension is to address the underlying cause of it, OK, treat the underlying disease process, and that will improve the pulmonary hypertension.
And if it's reversible, the underlying disease process, we can reverse the pulmonary hypertension and potentially even all of that right sided, you know, cardiomegaly and pulmonary arterial dilation that we've seen on these echocardiograms, these patients can completely reverse, remodel, and return to normal in some instances. So pulmonary arterial hypertension, well, you know, for the main part, a lot of these patients are those with congenital heart disease, so they'll be referred to a cardiologist, you know, for appropriate sort of management, whether that's with interventional procedures, you know, or medical. Idiopathic pulmonary hypertension is treated primarily with sildanafil, which we're going to go on to in a second.
Type 2 disease, left-hand sided heart disease, and essentially the vast majority of patients, we just need to optimise the treatment of their left-sided heart disease. So if they have active congestive failure, we're going to increase diuretic therapy. If they're, you know, not yet on heart medications, we're going to look at whether or not they would benefit from a positive ionotrope, like pink bendin, which we now know a lot of patients with clinical canine patients with clinical and pre-clinical heart disease will benefit from.
Whether or not they'll benefit from ACE inhibitors, from lactone therapy, antiarrhythmic rate control therapy, these sorts of things. And normally just by optimising treatment of the left sided heart disease, we will significantly improve their pulmonary hypertension, and it's often really quite uncommon that we need to specifically treat the pulmonary hypertension in those patients. And respiratory disease, hypoxia or both.
And of course we need to diagnose and treat the underlying disease process and then decide on how aggressively we may or may not need to treat the pulmonary hypertension. And if we've got patients with diseases like ear xenophilic bronchorneumopathy. They can present with pulmonary hypertension, but you treat that is in a bronchneumopathy, you know, with high dose glucocorticoid therapy initially oral and inhaled.
Those patients can have significant resolution of their respiratory disease, and then, you know, they can have resolution of their pulmonary hypertension as well and not necessarily require therapy. But there are those patients that aren't so fortunate. So we've said the Westies with, Westie Lung, for instance.
You know, there are no definitive treatment options for their, pulmonary fibrosis, and those patients, you know, end up on. Various medications for their, pulmonary fibrosis, which is often, complemented with sannophil citrate, if they have got clinically significant, pulmonary hypertension. Pulmonary thromboemboli, these patients.
You know, require sort of quite thorough investigation and treatment of the underlying cause of their thromboembolic disease, you know, whether it's a protein losing nephropathy or IMHA, will require as well. Antithrombotic, therapy. So, often it's a combination of antiplatelet drugs, most commonly clopidogrel and anticoagulants, which, you know, most commonly are the, the 10A inhibitors like rivaroxaban, they're often used in combination, until there is sort of clot resolution, which, you know, will occur in the vast majority of patients.
And those patients. May require therapy of their pulmonary hypertension, whilst that clot is in situ and causing problems. But, given enough time, normally that clot, you know, will disappear.
And those patients, if they do survive the event, can reverse remodel. And that's exactly what happened in that example of that cat that I showed you. You know, that patient was on 6 to 8 weeks of antithrombotic therapy and sildenafil citrate, and essentially we re-echoed, thrombus had completely gone, heart had reversed, remodelled.
The patient was titrated off therapy and signed off, you know, as a back to normal cat long term. Type 5 parasitic disease, so these patients, again, they, you know, can have complete resolution of their parasitic disease and all of the complications of that. So particularly with and your stronglus Zorum.
You know, you can see cases who've got right-sided heart failure because of pulmonary hypertension that go on to treatment with anti-parasitics, and they have complete reverse remodelling of the heart and can return to being normal, and may require transient or adenophil therapy. If severe enough during that period, but actually, you know, unfortunately as well, quite a few of those patients, you know, aren't as lucky and there may not be complete reverse remodelling, you know, of the changes that have been caused by the parasitic lung disease. So these patients often require sort of quite a bit of monitoring in the short and long term.
To see how responsive they are to antiparasitic therapy and how much reverse remodelling occurs. So just onto silannophil citrate, just to finish up. So this is the treatment of choice for pulmonary hypertension.
It's a phosphodiestrase 5 inhibitor and it preferentially vasodilates the pulmonary arteries, and that, of course, reduces the pulmonary vascular resistance. And can reduce the pulmonary pressures and and therefore the severity of the clinical signs associated with the pulmonary hypertension. Now what we know about this drug is that it is generally pretty well tolerated, .
It has been shown in studies in quite a few different diseases to significantly improve clinical signs, exercise tolerance, and quality of life in individuals that are on that drug. And however, it hasn't consistently been shown to improve the estimated pulmonary arterial pressure. So what that means is that We use this drug and we look for clinical improvement in the patients, OK, as described by the owners or observed by ourselves, and we can, you know, serially monitor the pulmonary pressure by estimating it with our echocardiogram measurements.
But even if we don't see a decrease in the estimated pressure, it doesn't mean the treatment isn't working. And the one reason why this might be occurring is that when we do vasodilate the lungs, we then decrease the afterload on the right ventricle, which increases the cardiac output of the right ventricle, increasing pulmonary vascular blood flow, and that increased blood flow might then. Mean that there is still the same degree of tricuspid regurgitation, OK, because the pressures remain the same, not because of increased pulmonary vascular resistance, but because of the increased blood flow, which is what we want to achieve in these patients, OK, the increased pulmonary flow.
So we can monitor them echocardiographically, and what we often see is that, you know, we start patients on sildenafil, and the sildenafil itself, in my experience, can sometimes, you know, drop the pulmonary arterial pressure by an average of sort of 30 millimetres of mercury, which can be really clinically significant in some individuals. And we administer sildenafil at a dose of anything from 0.5 to sort of 2.7 gigs per per day.
So we give it 3 times daily cos it's got really quite a short half-life. And you know, we start out generally most patients with a median dose of about 1 week per gig, you know, 3 times a day, and then we can up titrate therapy from there depending on how severe the patient is, depending on what their condition is, how acute it is versus how chronic it is, we'll sort of determine at what rate we might change the therapy. But one thing to bear in mind is that, Sudenoil can be very beneficial but can potentially be deleterious as well.
So patients who've got type one disease because of, congenital shunts. So these patients, if they have got right sided, sorry, pulmonary hypertension, and it's really quite severe and we're developing right to left shunting, you know, some of those patients can benefit from sildenafil therapy, and that's definitely the kind of thing that should be prescribed by a cardiology specialist. Patients who do have left to right shunting, you know, it can be deleterious, starting those individuals on silannafil, and patients as well with left-sided heart disease.
We have to be very cautious about starting sildenafil therapy in these individuals, and the reason being that if their left sided heart disease is not well controlled, they've got high left sided filling pressures, perhaps they've got a small amount of pulmonary edoema. If we vasodilate the pulmonary arteries and increase the blood flow through the lungs and increase the blood flow to the left side of the heart. That increased volume of blood combined with the elevated left-sided filling pressures because the left sided heart disease can precipitate pulmonary edoema in these individuals.
So essentially you can have a patient that's got early, you know, congestive heart failure and pulmonary hypertension, if you start them on sildenafil therapy, you can significantly worsen their pulmonary edoema. So we always have to be sort of cautious in those patients and when we do start, Sodenofi in patients with the left sided heart disease, we start towards the lower end of the dose range and we sort of cautiously up titrate the dose over time. So, thank you all for listening.
I hope there are a few sort of, take home messages there. I think the important things that I wanted to hammer home is that. Pulmonary hypertension is out there and it is perhaps a lot more common than you may think.
And what you need to do as clinicians is having in your head this sort of I guess Group of clinical signs. And group of diseases which could all be associated with pulmonary hypertension and In the next patient that you think could have pulmonary hypertension, you know, it's well worth you getting that patient screened for it, whether it's at your clinic or somewhere else. To see if they have this really clinically significant complication of many of the diseases because if they do, and it's left untreated, that patient won't have a particularly good outcome.
Whereas if it is detected, diagnosed and treated, these patients can, you know, do a lot, lot better. So many thanks for listening and I'll see you all next time.