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VETcpd - Cardiology

Cyanotic heart diseases in dogs: when erythrocytosis becomes problematicThe diagnostic approach to erythrocytosis involves an understanding of the basic physiology and differential diagnoses for why this can go wrong. In this article, we cover the essentials of background understanding for approaching a dog with erythrocytosis, then delve deeper into a common cause for erythrocytosis in young dogs – complex cardiovascular disease. With real-life case examples, we will review various treatment options for how to manage these challenging but rewarding patients.

Key words: congenital heart disease; echocardiography; pulmonary hypertension; hirudotherapy

Kieran Borgeat BSc BVSc MVetMed CertVC FHEA MRCVS DipACVIM DipECVIM-CA (Cardiology). Clinical Lead in Cardiology, Langford Vets. American Specialist in Veterinary Cardiology. EBVS® European Veterinary Specialist in Small Animal Cardiology. RCVS Recognised Specialist in Veterinary CardiologyKieran worked in first opinion and emergency practice before undertaking a Residency in Cardiology. He is an American and European Diplomate, with particular interests in interventional surgery and feline cardiomyopathy. He has spoken internationally on feline cardiology, interventional radiology and other cardiac topics, and tries to provide bite-sized interesting cardiology content on Instagram, via @vet_cardio_

IntroductionCongenital heart diseases are mostly easy to identify in dogs. The most common congenital heart diseases, pulmonic stenosis, subaortic stenosis and patent ductus

arteriosus (PDA), are all associated with loud murmurs when the problem is severe. Together, these three disorders make up around 90% of congenital heart disease in dogs. Once a heart murmur is identified, echocardiography can follow swiftly in-house or by referral to a cardiologist, in order to determine the disease severity and what can be done. In the hands of an experienced team, interventional surgery carries a good prognosis for the majority of these cases.

Not all dogs with congenital heart disease have such a straightforward problem, however. A number of cases have large septal defects or may be complicated by pulmonary hypertension. These are often referred to as “complex congenital heart diseases”, and they make up less than 5% the congenital heart problems diagnosed. They can be tricky to detect in puppies presenting for routine healthcare, because the alterations in intracardiac pressure or blood viscosity that occur will reduce the likelihood of loud heart murmurs being detected. How do we know that the small puppy in front of us is not just the “wee one” of the litter, but has had their growth stunted by congenital heart disease? Because of these difficulties, complex congenital heart disease may not be diagnosed until later in life, when clinical signs of its consequences

become manifest, such as those caused by erythrocytosis. Despite this, most dogs with cyanotic heart disease can tolerate their malformation for years so long as blood flow is maintained and haematocrit is controlled.

Here, we will review briefly how to approach dogs with erythrocytosis, and consider some cases of congenital heart diseases which can lead to erythrocytosis occurring. Treatment and follow-up will be discussed.

Defining erythrocytosisErythrocytosis is the term used for increased packed cell volume or haematocrit (HCT). Polycythaemia is another term in common use but this originates from a condition known as polycythaemia vera, a neoplastic cause of erythrocytosis; so the latter term will be used to avoid confusion. It is defined as HCT >55% not caused by dehydration – so represents an absolute (rather than relative) increase in red blood cell mass. Breed-specific increases in HCT should be considered prior to diagnostics (sighthounds especially), as should dehydration by comparing HCT with total protein. If in doubt, intravenous fluids can be provided and the patient reassessed after a few hours to look for a reduction in HCT to a more appropriate level. Although true erythrocytosis is uncommon in dogs, it is an important condition to consider. Congenital heart disease is an important cause, but is not the only reason a dog may present with erythrocytosis (see Apendix 1, page 15).

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VETcpd - Cardiology

Clinical signs caused by erythrocytosis tend to occur when HCT exceeds 70-75%. This causes “hyperviscosity syndrome”: where the flow of blood through capillaries becomes sluggish and the patient is in a hypercoagulable state. Microthrombi can form and block capillary beds, or simply the viscous mass of red cells passes so slowly through tissue that ischaemia results. Seizures can result, as can muscle pain and fatigue.

Cyanosis, a grey or blue-tinged colour to mucous membranes, occurs when the concentration of deoxyhaemoglobin in the circulation reaches 5g/dL. In animals with erythrocytosis, the circulating concentration of deoxyhaemoglobin will be higher at normal levels of cardiorespiratory function. This means that, whilst dogs with a normal HCT have to experience severe respiratory compromise to become cyanotic, those with high HCT can demonstrate cyanosis on room air. For this reason, the heart diseases which are associated with erythrocytosis are often called “cyanotic heart disease”.

Erythrocytosis can be considered primary or secondary. The only primary cause seen with any frequency in dogs or cats is polycythaemia vera, a proliferative neoplastic disorder of the bone marrow erythroid line. Secondary erythrocytosis is caused by a normal response to increased erythropoietin – the hormone released by the kidney in response to hypoxaemia, and responsible for modulating red blood cell production. This means that any disorder causing prolonged hypoxaemia can trigger a secondary “appropriate” erythrocytosis. Other causes include various kidney diseases and a paraneoplastic condition (secondary, inappropriate causes).

Investigation of a dog with true erythrocytosis should include the following, in order:

1) Screen for causes of hypoxaemia: cardiovascular or respiratory disease

2) Screen for evidence of renal disease: neoplastic or non-neoplastic

3) Screen for evidence of neoplasia elsewhere

4) If no identifiable trigger during the above testing, erythrocytosis is likely to be caused by polycythaemia vera – bone marrow aspirates or biopsy are not helpful, so this must be a diagnosis of exclusion

Cardiovascular causes of erythrocytosis Generally speaking, congenital heart diseases associated with erythrocytosis feature a large septal defect (atrial or ventricular) in combination with something that raises pressure in the right heart to the same level or above that in the left heart, such as pulmonic stenosis or pulmonary hypertension. If right heart pressure were normal, then blood would flow from systemic to pulmonary vasculature, therefore not causing prolonged hypoxaemia (so HCT would not increase – the dog would simply go into left-sided heart failure and develop pulmonary oedema; as occurs in a left-to-right PDA). A minority of cases may have another reason for deoxygenated blood to enter systemic circulation in significant quantities, such as aberrant venous drainage to the left heart.

Pulmonary hypertension (PH) is a condition where resistance to blood flow through the lungs is increased, so right ventricular afterload (the pressure that the heart has to push against) will increase. In the short term, this tends to occur because of vasoconstriction of arterioles. Most often, this is a response to 1) increased flow in the pulmonary arterial bed, e.g. large intracardiac shunt; vasoconstriction probably occurs as a protective mechanism to limit pulmonary flow and reduce risk of pulmonary oedema; 2) chronic increase in pulmonary venous pressure, e.g. in chronic mitral valve disease, again as a protective mechanism; or, 3) respiratory disease causing hypoventilation of lung tissue, because of the response of pulmonary vessels to only perfuse well ventilated regions. Considering these factors, we can see how the main differentials for dogs with PH are 1) congenital heart disease, 2) advanced mitral valve disease and, 3) severe respiratory disorders.In the first weeks of PH, vasoconstriction predominates and therefore the PH can be reversed by using drugs that reduce pulmonary vascular resistance (e.g. sildenafil). With chronicity comes vascular fibrosis and anatomic change to blood vessel structure (intimal fibrosis and medial hypertrophy), which reduce lumen diameter without expending the energy to actively vasoconstrict. Sadly, much of this advanced change is irreversible, so response to pulmonary vasodilators will be reduced in dogs with more longstanding disease and prognosis will be poorer because of this.In endemic countries, Dirofilaria immitis is an important and common cause of PH, and in the UK Angiostrongylus vasorum may also cause PH in a low number of cases. Thromboembolic disease can also cause PH, owing to chronic, widespread obstruction of vessels.Pulmonary hypertension is best diagnosed using echocardiography, where Doppler measurements can be used to estimate pulmonary artery pressure in systole (and sometimes diastole). The gold-standard for measurement is to place an invasive pulmonary artery catheter, but this is impractical in most clinical patients. Normal pulmonary systolic pressure is up to 30 mmHg, and dogs are classified as moderate to severe PH where estimates exceed 60 mmHg.

Congenital heart diseases causing erythrocytosis in dogs• Pulmonic stenosis with large ventricu-

lar septal defect (VSD)• Pulmonic stenosis with patent foramen

ovale (PFO)• Pulmonic stenosis with large atrial

septal defect (ASD)• Pulmonary hypertension (Box 1)

with large VSD• Pulmonary hypertension with

large ASD• Pulmonary hypertension with PFO• Atrioventricular septal defect• Tetralogy of Fallot• Double-outlet right ventricle• Double-chamber right ventricle with

large VSD• Persistent truncus arteriosus• Right-to-left PDA; cyanosis affects the

caudal body only

Box 1: What is pulmonary hypertension?

Dirofilaria immitis (courtesy of Bayer).

Angiostrongylus vasorum (Bayer).

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VETcpd - Cardiology

Case 1: Bertie, the French Bulldog

Bertie presented with erythrocytosis (HCT 73%) and a grade IV/VI systolic heart murmur at the left base. On echocardiography, he was diagnosed with

severe pulmonic stenosis (hypoplastic pulmonary artery and right ventricular hypertrophy) and a large ventricular septal defect (Figure 1). The aorta was positioned above the VSD. Flow could be seen moving from right to left in systole, so from the deoxygenated blood in the right ventricle to the systemic circulation (aorta). This is enough to explain his HCT and the reported cyanosis episodes. Diagnosis was tetralogy of Fallot (Box 2). Treatment in this case was to perform a modified Blalock-Thomas-Taussig shunt (Box 3); essentially create a PDA using a synthetic conduit between the systemic and pulmonary circulation, from the left subclavian artery to the left pulmonary artery. This increases pulmonary blood flow and gives a “second chance for oxygenation”. In many cases, this significantly reduces hypoxaemia and controls erythrocytosis. In this case, Bertie’s HCT reduced to 46% 4-weeks post-operatively.

Case 2: Haddaway, the Jack Russel terrier

Haddaway was referred after the incidental detection of a grade III/VI systolic heart murmur led to thoracic radiographs at his local vets and

the detection of marked cardiomegaly. Echocardiography showed a huge atrial septal defect and some abnormalities of the atrioventricular valves; the tricuspid apparatus was at the same level as the mitral (should be apically displaced), and the anterior mitral leaflet appeared cleft (Figure 2). These findings are typical for an abnormality called at atrioventricular septal defect (AVSD), where the region of the low inter-atrial septum, high-ventricular septum and the valves do not form properly, and leaves defects in one or more parts of this anatomy. In this case, no ventricular septal defect was identified (referred to as an “atrial dominant AVSD”. Because of the large shunt from left atrium to right atrium during early life, pulmonary hypertension is a common consequence, and here it was severe enough to cause a bi-directional shunt

through the AVSD and massive right heart dilation. Haematocrit measured 67%.

Aside from a primary surgical repair, which could only reasonably be attempted in one or two centres worldwide, there is no good treatment for cases like Haddaway. The best we can hope for is control of pulmonary hypertension (using the pulmonary vasodilator, sildenafil, a PDE-V inhibitor) and control of HCT to a reasonable level.

Case 3: Milka, the English Bulldog

Milka presented very severe exercise intolerance, cyanosis and a grade II/VI intermittently detected heart murmur. Echocardiography showed

severe pulmonic stenosis and a large ASD (Figure 3). A large right-to-left shunt was present at the atrial level, and HCT was 79%. The defect was in the mid-septum, typical of a septum secundum defect. These often have a reasonable ridge of tissue around the defect, which is suitable for device closure – as was the case for Milka.

Pulmonic balloon valvuloplasty was performed to relieve the stenosis, and an atrial septal occluder device was placed to close the ASD via the jugular vein and prevent complications caused by an ongoing shunt (in either direction). At 4-weeks post-procedure, HCT had reduced to 41%.

Case 4: Charlie, the Cavalier King Charles Spaniel

Charlie had a grade V/VI left sided basilar heart murmur with a palpable pre-cordial thrill. Echocardiography showed a severe valvular pulmonic

stenosis and a PFO which was subject to a right-to-left shunt at the atrial level (Figure 4). He had erythrocytosis, with HCT at 69%. After pulmonic balloon valvuloplasty, the reduction in right ventricular pressure was enough to allow closure of the PFO (Box 4). Haematocrit has normalised to 38% at 4-weeks post-operatively.

Tetralogy of Fallot (ToF) is a congenital heart disease characterised by four findings:• A large VSD• Mispositioning of the aorta over the

septum, straddling both ventricles• Pulmonary artery hypoplasia, causing

stenosis• Right ventricular hypertrophy

Although Fallot became famous by reporting this quadruple finding at necropsy in 1888, Stenson had previously reported the same condition as series of consequences from simply having a large VSD in 1672 – the aortic root falls to the right because of a lack of support, compresses the pulmonary artery during foetal growth to cause under-development, and then the right heart thickens because of pressure overload owing to exposure to not only a stenotic pulmonary trunk but also systemic pressures in the aorta. Cardiologists often make a niche joke by referring to the condition as “Monology of Stenson” – a testament to how a funky name can leave you more famous than the person who accurately described the pathophysiology over 200 years earlier.

Box 2: What is tetralogy of Fallot?

In the first decades of the 20th Century, large numbers of children with ToF were dying young because of the consequences of severe hypoxaemia. These so-called “blue babies” seemed to have no good option for help. At John Hopkins Medical Center in the USA, a pioneering team developed a surgical procedure to help provide a better quality of life and longevity for these children. Alfred Blalock, a surgeon, worked alongside Helen Taussig, a cardiologist who devised the procedure. Vivien Thomas, an African-American laboratory assistant of great skill and dedication, pioneered the surgical technique in canine models and developed his skills to become a world-leading heart surgeon. In the first human surgery performed, on a 15-month-old girl with ToF in 1944, Thomas instructed Blalock on how to perform the procedure and changed the face of cardiac surgery forever. Despite this, owing to racial prejudice, Thomas’ name was not part of the “Blalock-Taussig shunt” for decades. Now, we must aim to acknowledge Vivien Thomas’ contribution to cardiology by naming him amongst the surgery’s creators.

Box 3: The shunt with three names

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