Genetic Welfare Problems of Companion Animals

Boxer

Aortic Stenosis 

Related terms: Aortic stenosis

VeNom term: Aortic stenosis (subvalvular aortic stenosis, subaortic stenosis)

VeNom code: 1925.

Related conditions: left ventricular hypertrophy, congestive heart failure, endocarditis, pulmonic stenosis, arrhythmia

Outline: Aortic stenosis is a condition of the heart in which there is a narrowing of the one of the valves of the heart that controls the flow of blood from the left ventricle of the heart to the aorta, a large artery that takes blood to the rest of the body. This narrowing interferes with the normal flow of blood and causes a partial obstruction. With severe narrowing, the resistance to the flow of blood may cause the left ventricle to enlarge and the muscle walls to become damaged. Affected dogs may suffer with an inability to exercise, fainting, muscle weakness, breathing difficulties, coughing, and fatigue and/or chest pain (angina). Severe forms and associated complications can lead to death in early adulthood.

Affected dogs are likely to have a heart murmur, but this may be mild in some dogs and they may not show obvious signs of being affected. A definitive diagnosis can be made by a cardiologist using a Doppler echocardiogram.

The Boxer breed has been shown to have an increased relative risk of the condition, compared to other breeds, which may be associated with breed specific conformational differences in the morphology of the aortic valve. Both males and females are affected. Aortic stenosis in the Boxer is likely to be a complex inherited disorder, involving multiple genes but the mode of inheritance is not currently known. Importantly, not all dogs which carry the affected genotype show outward clinical signs and there are a range of severities of affected dogs from mild to severe. Moderate-severely affected dogs should not be bred from.

Summary of Information

(for more information click on the links below)

1. Brief description

Aortic stenosis is a condition of the heart in which there is a narrowing of the one of the valves of the heart that controls the flow of blood from the left ventricle of the heart to the aorta, the large artery that takes blood to the rest of the body. The condition is characterised by an abnormal ring of tissue at the valve which interferes with normal blood flow, creating resistance to the passage of blood and causing an obstruction.  The severity of the abnormal lesion can range from mild to severe, from an incomplete ridge of fibrous tissue to an extensive fibrous band encircling the aorta.

A heart murmur, which is an abnormal sound of blood rushing through the valve when the heart contracts, is heard in dogs with the condition since there is turbulent flow through the obstructed valve. The degree of murmur, and its duration correlates with the severity of aortic stenosis.

 The heart is a complex organ and this obstruction can lead to various ‘knock on’ problems which, at some stage, prevent the heart from functioning normally. Exactly what happens in an individual depends on the degree of obstruction of the aorta, whether or not other valves of the heart are affected, and the degree to which conduction of heart beat signals are interfered with. The consequences of various manifestations of the disease are outlined below.

• When resistance to the flow of blood is high, the left ventricle has to contract more forcefully to expel the blood and this causes high ventricular pressures which may cause the left ventricle wall to become thickened and lead to damage. The reduced flow of blood past the stenotic valve can cause abnormally low blood pressure in the rest of the body (hypotension).
• The obstruction may be so severe that the left ventricle, and thus the rest of the heart may fail to empty. This causes a backflow problem so that blood cannot enter the heart normally. This is backward or congestive heart failure. The result is fluid build-up in the lungs (pulmonary oedema).
• As the walls of the left ventricle thicken the heart shape changes and the valves of the heart can become distorted and leak. When the valves, the tricuspid and mitral valves, between the ventricles and atria are affected, they may allow blood to flow backwards into the atria during contraction which causes further backwards (or back pressure) heart failure problems and the problems, outlined above, associated with this.

The abnormally thickened muscle often contains scar tissue or fatty infiltrates which interfere with the conduction of nerve signals through the heart resulting in uncoordinated contractions (dysrhythmia or arrhythmia). Irregular heartbeats can contribute to both forward and backward heart failure. Forwards heart failure occurs when the left ventricle provides inadequate blood flow to the body and this can lead to weakness, collapse, fainting and sudden death.

2. Intensity of welfare impact

The degree to which a dog is affected by aortic stenosis is usually graded on a mild, moderate, severe scale. Dogs with mild aortic valve narrowing, which does not progress, may have a normal lifespan, with very few changes to quality of life.

Dogs that are moderate to severely affected by the condition may experience serious welfare problems. They may exhibit an inability to exercise, fainting and muscle weakness. The build-up of fluid in the veins which transport blood through the lungs, leads increased pressure in these blood vessels, which pushes fluid into the air spaces of the lungs, reducing the normal movement of oxygen through the lungs. This results in the animal showing rapid or laboured breathing. Other signs are fatigue and/or chest pain (angina).

Affected dogs may be at risk of complications such as changes in heart rhythm (arrhythmias), congestive heart failure - where the heart is unable to pump blood effectively around the body - or infections of the inner lining of the heart (endocarditis), caused by bacterial infiltration due to the defective/damaged heart valves that control the movement of blood from one chamber of the heart to another.

3. Duration of welfare impact

Aortic stenosis is often a progressive disorder, and severe forms can lead to death in early adulthood. Dogs that reach adulthood with only mildly abnormal lesions are likely to live normal lives.

Definitive treatment for severe aortic stenosis requires surgical intervention before 6 months of age for greatest success. Palliative treatment, which aims to relieve the condition rather than to cure it, includes the use of drugs to slow the rate of left ventricular hypertrophy and/or to smooth out irregular heart rhythms.

4. Number of animals affected

The prevalence of aortic stenosis in dogs is currently unknown but the Boxer breed has been shown to have an increased relative risk of the condition. Both males and females can be affected with aortic stenosis.

5. Diagnosis

The identification of a heart murmur can indicate aortic stenosis. Initial diagnosis is commonly done by a veterinarian listening with a stethoscope. Murmurs are categorised on a six point scale from Grade 1, the mildest and least audible, which can be heard with a stethoscope only in a quiet room, to Grade 6, the loudest and most turbulent, which can be heard with the stethoscope not touching the chest, or even without using the stethoscope. If a murmur is detected, then confirmation can be achieved through further stethoscopic examination or, more definitively, using Doppler echocardiography. Echocardiography can be used to evaluate: heart size, function including the direction and speed of blood flow, and valve appearance. Other diagnostic tools used to determine the severity of the disease and the presence of heart failure, include: ECG recordings, blood tests, chest radiography and full physical examination.

6. Genetics

Boxers have a higher risk of developing aortic stenosis but the exact genetic mechanism or mode of inheritance in this breed has not been identified. The inheritance pattern is suspected to be complex and involve multiple genes.

7. How do you know if an animal is a carrier or likely to become affected?

There is currently no way of telling specifically which animals are likely to become affected. Importantly, not all dogs which carry the genotype show outward clinical signs and there is a range of severities of affected dogs from mild to severe.

8. Methods and prospects for elimination of the problem

It is important to identify affected dogs, even those with mild forms, for the purpose of eliminating the condition from the breed. Dogs should be screened for heart murmurs, and those with grade 3 murmurs or higher should not be bred from.

For further details about this condition, please click on the following:
(these link to items down this page)

• Clinical and pathological effects
• Intensity of welfare impact
• Duration of welfare impact
• Number of animals affected
• Diagnosis
• Genetics
• How do you know if an animal is a carrier or likely to become affected?
• Methods and prospects for elimination of the problem
• Acknowledgements
• References

1. Clinical and pathological effects

The heart is a four-chambered pump which is divided into left and right sides. Each side has two chambers: blood enters into the thin-walled upper chamber (atrium). It then flows into the larger, lower chamber (ventricle). The ventricles have thick walls composed largely of heart muscle. Between the chambers of the atria and the ventricles there are valves that prevent blood flowing backwards from the latter to the former. On contraction, blood flows from the ventricles into the major blood vessels. There are also valves at the junction of the ventricles and these blood vessels that preventing blood flowing backwards.

The right side of the heart receives blood from the whole of the body other than the lungs, via the venae cavae. The blood accumulates in the right atrium and during a heart beat it is sucked past the tricuspid valve into the right ventricle and then as the right ventricle contracts (squeezes) its muscular wall, the blood is pushed through the pulmonary valves into the pulmonary arteries that take it onto the lungs (to take up oxygen).

The left side of the heart receives this oxygenated blood from the lungs, via the pulmonary veins. The blood accumulates in the left atrium and during a heartbeat it is expressed past the mitral valve into the left ventricle. Then, as the muscular wall of the left ventricle contracts, the blood is pushed through the aortic valves into the aorta and onto the other major arteries which carry it around the body to perform all the functions of blood circulation such as delivering oxygen and nutrients and sharing heat and metabolic products throughout the body.

So, the left hand side of the heart has to pump blood around the major organs of the body, whilst the right hand side only has to push blood through the adjacent lungs. This difference does not affect the structure and function of the atria very much but requires that the muscles of the left ventricle have to be much stronger than the right. As strength is largely a function of muscle size the muscle wall of the left ventricle is thicker than the right

Aortic stenosis is a condition of the heart in which there is a narrowing of the aortic valve of the heart that controls the flow of blood from the left ventricle. The condition is characterised by an abnormal ring of tissue at the valve which interferes with normal blood flow, creating resistance to the passage of blood and causing an obstruction 

The lesion of aortic stenosis in the dog commonly occurs in the subvalvular position, and thus the condition is called subaortic stenosis. The severity of the lesion can range from mild to severe, from an incomplete ridge of fibrous tissue to an extensive fibrous band encircling the aorta.

A heart murmur, which is an abnormal sound of blood rushing through the valve when the heart contracts, is heard in dogs with the condition since there is turbulent flow through the obstructed valve. The degree of murmur, and its duration correlates with the severity of aortic stenosis (Kvart et al 1998). 

The heart is a complex organ and this obstruction can lead to various ‘knock on’ problems which, at some stage, prevent the heart from functioning normally. Exactly what happens in an individual depends on the degree of obstruction of the aorta, whether or not other valves of the heart are affected, and the degree to which conduction of heart beat signals are interfered with. The consequences of various manifestations of the disease are outlined below.

• When resistance to the flow of blood is high, the left ventricle has to contract more forcefully to expel the blood and this causes high ventricular pressures which may cause the left ventricle wall to become thickened and lead to damage. the left ventricle may need to contract more forcefully to effectively move blood forward into the aorta, and so the muscular walls of the left ventricle become thicker (myocardial hypertrophy) and this causes high ventricular pressures. As a result of this abnormally high ventricular pressure, the intramural coronary arteries - which supply the muscles of the heart with blood- will thicken and collapse, and the muscle wall of the left ventricle will start to degrade (necrosis) and scar tissue will form (fibrosis). Eventually, the cardiac tissue does not receive adequate blood flow and thus does not receive enough oxygen for normal function (myocardial ischemia and hypoxia). Heart failure may start to occur since the heart is unable to pump enough blood through the narrow valve to meet the requirements of the body.
• The reduced volume of blood past the stenosis valve causes abnormally low blood pressure in the rest of the body (hypotension).

The body is able to compensate, to some extent, for impending heart failure using various mechanisms although some of these can themselves lead to further problems.

• When there is inadequate blood flow from the heart, heart rate is increased so that blood supply to the organs is maintained. However, this raised heart rate may restrict the ability of the ventricles to relax as there is less time between each contraction; time in which the ventricles can relax and fill. Increasing heart rate can cause backward or congestive heart failure, in which fluid builds up in the lungs (pulmonary oedema) and in which the amount of blood that the heart can push forwards around the body decreases. A further problem is that it is during relaxation that the heart muscle itself receives blood via its coronary arteries so when beating quickly its own oxygen supply can decrease and heart muscle can die.

Inadequate blood flow from the heart also causes the body to react as though there has been a loss of circulating blood volume. Hormones are released in response, which cause fluid to be retained even though there actually has been no loss of blood. The amount of fluid in the body thus increases and this is another reason that fluid accumulates in the lungs.

• As the walls of the left ventricle thicken the heart shape changes and the valves of the heart can become distorted and leak. Leakage (regurgitation) of blood in the reverse direction from the aorta back into the left ventricle, and this may manifest in a diastolic murmur (Schaer 2010). When the valves, the tricuspid and mitral valves, between the ventricles and atria are affected, they may allow blood to flow backwards into the atria during contraction which causes further backwards (or back pressure) heart failure problems and the problems, outlined above, associated with this.
• The abnormally thickened muscle often contains scar tissue or fatty infiltrates which interfere with the conduction of nerve signals through the heart resulting in uncoordinated contractions (dysrhythmia or arrhythmia). Irregular heartbeats can contribute to both forward and backward heart failure. Forward heart failure occurs when the left ventricle provides inadequate blood flow to the body and this can lead to weakness, collapse, fainting and sudden death.

Other congenital heart abnormalities may be associated with aortic stenosis, including pulmonic stenosis, and atrial septal defect (Oliveira et al 2011), though more often than not aortic stenosis occurs alone. Affected dogs may also be at risk of complications such infections of the inner lining of the heart (endocarditis), caused by bacterial infiltration due to the defective valve.

In one study, a smaller aortic annulus (at the junction of the aortic valve and ventricular septum) and a steeper aortoseptal angle relative to body size was notable in both healthy and affected Boxers, and these may be key factors for the development of aortic stenosis (Quintavalla et al 2010). These findings have also been observed in other breeds susceptible to aortic stenosis (eg Dogue de Bordeaux; Höllmer et al 2008).

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2. Intensity of welfare impact

The severity of aortic stenosis is usually graded as mild, moderate and/or severe in accordance with the lesion type and clinical symptoms (Pyle et al 1976). Dogs with mild narrowing, which does not progress, may have a normal lifespan, with very few changes to quality of life.

Dogs that are moderate-severely affected by the condition may experience serious welfare problems. They may exhibit an inability to exercise, fainting and muscle weakness. The build-up of fluid in the lungs, due to pulmonary odema, leads to difficulty in breathing with the animal showing rapid or laboured breathing or coughing. Where the heart muscles receive reduced oxygen as a result of the obstructed blood flow (myocardial ischemia and hypoxia), dogs may experience fatigue or chest pain (angina).

Affected dogs may be at risk of complications such as changes in heart rhythm (arrhythmias) – which in themselves may directly cause welfare problems by making the dog faint or collapse - congestive heart failure or infections of the inner lining of the heart (endocarditis). In one study of Boxer with aortic stenosis, infective endocarditis and left heart failure tended to occur later in life and in dogs with mild to moderate obstructions (Kienle et al 1994). These complications may lead to sudden death.

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3. Duration of welfare impact

Aortic stenosis is not a true congenital defect, since it develops after birth (Pyle et al 1976). Aortic stenosis is often a progressive disorder, and the severe forms can lead to death in early adulthood. In one study of 96 Boxers with aortic stenosis, 21 dogs (21.9%) died suddenly, and this sudden death usually occurred in the first 3 years of life (Kienle et al 1994). However, once the dog is mature, the rate of stenosis progression slows considerably, and therefore for dogs reaching adulthood with mild lesions are likely to live normal lives (O’grady et al 1989).

The prognosis for long-term survival of dogs with untreated mild or moderate aortic stenosis if favourable, with an average (median) survival of 4 years 3 months and 2 years 6 months respectively, but the survival of dogs with severe aortic stenosis was poor, with an average survival of  1 year 7 months (Kienle et al 1994).

Definitive treatment for severe aortic stenosis requires surgical intervention, either excision of the lesion or replacement of the valve, but the surgery should be performed before 6 months of age for greatest success (Muir et al 1989). Palliative treatment, that aims to relieve the symptoms rather than to cure it, include the use of drugs to slow the rate of left ventricular hypertrophy and/or to smooth out irregular heart rhythms.

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4. Number of animals affected

The true prevalence of aortic stenosis in dogs is currently unknown, since the previous studies are based on small, local, veterinary populations. Heart murmurs are commonly reported in dogs; over a 4-year period in the UK, 39.4 dogs per 1000 were diagnosed with a heart murmur and 8.8 dogs per 1000 with heart disease (VetCompass cardiovascular system data: http://www.rvc.ac.uk/vetcompass/learn-zone/infographics/canine). However, it is important to note that these heart murmur data are not specific to aortic stenosis, and that not all heart murmurs point to significant cardiac disease.

Aortic stenosis has been reported to be one of the most frequently recorded congenital cardiac abnormalities in the dog (Tidholm 1997). Of dogs with aortic stenosis, the Boxer breed has been shown to have an increased relative risk of the condition, with an odds ratios of 9.4 (Oliveira et al 2011) and 8.6 (Kienle et al 1994) being reported in Italy and California, respectively.

A prevalence of 1.3% was reported for aortic stenosis in Boxers in the Netherlands, which is small, but the mortality of dogs affected was high (41.7%; Nielen et al 2001). As part of a mandatory breed screening programme in Italy, Boxers were screened for cardiac abnormalities and 109 of 1283 Boxers (8.5%) were diagnosed with aortic stenosis, and 33% of these had a moderate to severe form (Bussadori et al 2009).

There is no reported difference in the predisposition of males and females for aortic stenosis.

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5. Diagnosis

Aortic stenosis is not usually diagnosable at birth but is diagnosed later on in the dog’s life. Initial diagnosis results from detection of a heart murmur using a stethoscope, although murmurs can be indicative of other heart conditions or even of normal function. Murmurs are categorised on a six point scale from Grade 1, the mildest and least audible, which can be heard with a stethoscope only in a quiet room to Grade 6, the loudest and most turbulent, which can be heard with the stethoscope not touching the chest, or even without using the stethoscope. Aortic stenosis can be definitively diagnosed by a cardiologist using a Doppler echocardiogram, which allows measurement of the velocity of blood flow across the valve (O’grady et al 1989. Echocardiographycan be used to evaluate: heart size, function including the direction and speed of blood flow, and valve appearance. Other diagnostic tools used to determine the severity of the disease and the presence of heart failure, include: ECG recordings, blood tests, chest radiography and full physical examination. ECG can be used to detect occult disease (eg heart rhythm abnormalities at a stage before animals show any clinical signs).

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6. Genetics

An inherited basis of aortic stenosis is strongly suspected in the Boxer, though there is no definitive data to support this. Boxers have a higher risk of aortic stenosis compared to other breeds, and there are specific conformational traits associated with the Boxer breed that affect the morphology of the aortic valve  (small aortic annulus, steep aortoseptal angle; Quintavalla et al 2010) which may be linked to the development of the condition.

To our knowledge, there are no studies of the genetics or mode of inheritance of aortic stenosis in Boxers.  Aortic stenosis is considered to be a dominant trait in Newfoundlands (Stern et al 2014) but in Golden retrievers, the condition is more likely to be a rescessive trait (Stern et al 2012). In both studies, authors also suggest that the inheritance pattern may be more complex and involve multiple genes, and especially considering the variation in age of onset and the lesion type and placement associated with the condition (Pyle et al 1976).

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7. How do you know if an animal is a carrier or likely to become affected?

Since the genetic mechanisms or mode of inheritance is not known for this breed, there is currently no way of telling specifically which animals are likely to become affected. Importantly, not all dogs that carry the genotype show outward clinical signs and there is a range of severities of affected dogs from mild to severe.

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8. Methods and prospects for elimination of the problem

Although dogs with a mild form of aortic stenosis have a low risk to develop symptoms of the condition, it is still important to identify these dogs for the purpose of eliminating the condition from the breed (Farrell et al 2015), since mildly affected and asymptomatic dogs may pass on a more severe form of the condition to their offspring.

Since 1990, a breeding scheme has been in operation in the UK for the Boxer breed, and it recommends cardiac screening for murmurs of dogs at 12 months or older. Dogs with grade 3 murmurs of higher are considered unsuitable for breeding, and dogs with grade 2 murmurs are only recommended for breeding with a dog clear of a murmur.

Further research is required to determine the mode of inheritance involved in the development of aortic stenosis in Boxers, in order to establish a valid method to eliminate the condition from the breed (Meyers-Wallen 2003).

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9. Acknowledgements

UFAW thanks Dr Emma Buckland (BSc PhD), Dr David Brodbelt (MA VetMB PhD DVA DipECVAA MRCVS) and Dr Dan O’Neill (MVB BSc MSc PhD MRCVS) for their work in compiling this section.

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10. References

 Bussadori C, Pradelli D, Borgarelli M, Chiavegato D, D’Agnolo G, Menegazzo L, Migliorini F, Santilli R, Zani A and Quintavalla C (2009) Congenital heart disease in boxer dogs: results of 6 years of breed screening. Veterinary Journal 181: 187–92

Farrell LL, Schoenebeck JJ, Wiener P, Clements DN and Summers KM (2015) The challenges of pedigree dog health: approaches to combating inherited disease. Canine Genetics and Epidemiology 2: 3

Höllmer M, Willesen JL, Jensen AT and Koch J (2008) Aortic stenosis in the Dogue de Bordeaux. The Journal of Small Animal Practice 49: 432–7

Kienle RD, Thomas WP and Pion PD (1994) The natural clinical history of canine congenital subaortic stenosis. Journal of Veterinary Internal Medicine 8: 423–431

Kvart C, French AT, Fuentes VL, Häggström J, McEwan JD and Schober KE (1998) Analysis of murmur intensity, duration and frequency components in dogs with aortic stenosis. Journal of Small Animal Practice 39: 318–324

Meyers-Wallen VN (2003) Ethics and genetic selection in purebred dogs. Reproduction in domestic animals 38: 73–6

Muir GD, Panciera DL, Fowler JD, Bharadwaj BB and Burrows P (1989) Medical and surgical management of aortic stenosis in a dog. The Canadian Veterinary Journal 30: 894–6

Nielen ALJ, Janss LLG and Knol BW (2001) Heritability estimations for diseases, coat color, body weight, and height in a birth cohort of Boxers. American Journal of Veterinary Research 62: 1198–1206

O’grady MR, Holmberg DL, Miller CW and Cockshutt JR (1989) Canine congenital subaortic stenosis: A review of the literature and commentary. The Canadian Veterinary Journal 30: 811–5

Oliveira P, Domenech O, Silva J, Vannini S, Bussadori R and Bussadori C (2011) Retrospective Review of Congenital Heart Disease in 976 Dogs. Journal of Veterinary Internal Medicine 25: 477–483

Pyle RL, Patterson DF and Chacko S (1976) The genetics and pathology of discrete subaortic stenosis in the Newfoundland dog. American Heart Journal 92: 324–334

Quintavalla C, Guazzetti S, Mavropoulou A and Bussadori C (2010) Aorto-septal angle in Boxer dogs with subaortic stenosis: an echocardiographic study. Veterinary Journal 185: 332–7

Schaer M (2010) Clinical medicine of the dog and cat, London, Manson/Veterinary Press

Stern JA, Meurs KM, Nelson OL, Lahmers SM and Lehmkuhl LB (2012) Familial subvalvular aortic stenosis in golden retrievers: inheritance and echocardiographic findings. Journal of Small Animal Practice 53: 213–216

Stern JA, White SN, Lehmkuhl LB, Reina-Doreste Y, Ferguson JL, Nascone-Yoder NM and Meurs KM (2014) A single codon insertion in PICALM is associated with development of familial subvalvular aortic stenosis in Newfoundland dogs. Human Genetics 133: 1139–48

Tidholm A (1997) Retrospective study of congenital heart defects in 151 dogs. Journal of Small Animal Practice 38: 94–98

© UFAW 2016

Credit for main photo above:

By Corporalen (Own work) [Public domain], via Wikimedia Commons