Genetic Welfare Problems of Companion Animals

An information resource for prospective pet owners

Newfoundland 

Newfoundland

Aortic Stenosis

Related terms: Subaortic Stenosis

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

VeNom code: 1925.

Related conditions: left ventricular hypertrophy, congestive heart failure

Outline: Aortic stenosis is a condition of the heart in which there is a narrowing of the one of the valves 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. 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 its muscle walls to become damaged. Affected dogs may suffer with an inability to exercise and may faint, and may exhibit muscle weakness, breathing difficulties, coughing, and fatigue and/or chest pain (angina). Severe forms and associated complications can lead to death in early adulthood.

The Newfoundland breed has been shown to have an increased relative risk of the condition compared to other breeds. Both males and females are affected.

Recent evidence has suggested that aortic stenosis in the Newfoundland is likely to be an inherited disorder with an autosomal dominant trait with variable penetrance. However, the inheritance pattern may be more complex and involve multiple genes which are currently undiscovered. Importantly, not all dogs that carry the affected genotype show outward clinical signs and there is a range of severities of affected dogs from mild to severe. 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 that transport blood through the lungs, leads to 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 in Newfoundlands is an acquired form of congenital heart disease, since the lesion progresses as puppies grow. Aortic stenosis is often a progressive disorder, and severe forms can lead to death in early adulthood. However, dogs reaching adulthood with mild 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 Newfoundland 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

Recent evidence has suggested that aortic stenosis in the Newfoundland is likely to be an inherited disorder with an autosomal dominant trait with variable penetrance. However, the inheritance pattern may be more complex and involve multiple genes which are not yet discovered.

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

With a dominant mutation, the defect can appear if a dog has at least one copy of affected DNA. If one parent carries one allele, half the offspring will carry at least one copy, and if both parents carry one allele, 75% of the offspring will carry at least one copy of DNA for the disorder. 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.

8. Methods and prospects for elimination of the problem

Prior to breeding dogs from breeds which are predisposed to congenital cardiac abnormalities, a cardiac examination by a veterinary surgeon should be made and if a heart murmur is detected then this should be investigated (though not all heart murmurs indicate significant disease). Since aortic stenosis is associated with a dominant trait, affected dogs should not be bred from, since there is a high chance of puppies carrying the gene and/or becoming affected themselves.

 

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


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 that 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 that 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 be at risk of complications such as infections of the inner lining of the heart (endocarditis), caused by bacterial infiltration due to the defective valve).

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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 feel ill, faint or collapse - congestive heart failure or infections of the inner lining of the heart (endocarditis). These complications may lead to sudden death.

Investigations into and treatments of heart failure may also have adverse welfare effects related to travel to and from veterinary practices, hospitalisations and medications – for example, medications may cause gastrointestinal disease.

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3. Duration of welfare impact

Aortic stenosis in Newfoundlands 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. 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).

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, includes 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 (Oliveira et al 2011; Tidholm 1997). The Newfoundland breed has been shown to have an increased relative risk of the condition (Oliveira et al 2011). It was found that 281 of 6023 (4.7%) Newfoundlands registered from the European and North American populations between 1976 and 2007, and which had a cardiac examination sufficient for diagnosis of aortic stenosis dogs were affected (Reist-Marti et al 2012). Of these dogs, almost half (49%) were severely affected. There was a peak in 1991, where 18.5% of puppies born that year were affected by aortic stenosis (Reist-Marti et al 2012). In an analysis of 88,600 dogs at a Veterinary teaching hospital in California between 1995 and 2010, it was found that pure-breed dogs were diagnosed with aortic stenosis in greater proportion compared with cross-breed dogs (Bellumori et al 2013), but that the greater risk was restricted to specific subsets of purebred dogs. Retriever-types, German shepherd dogs and mastiff-like dogs were at greater risk of aortic stenosis than other purebreds and mixed breed dogs (Oberbauer et al 2015).

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.

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 Doppler echocardiography, which allows measurement of the velocity of blood flow across the valve (O’grady et al 1989. 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. 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

Recent evidence has suggested that aortic stenosis in the Newfoundland is likely to be an inherited disorder with an autosomal dominant trait with variable penetrance (Stern et al 2014). The researchers found an insertion in the phosphatidylinositol-binding clathrin assembly protein (PICALM) that is associated with the development of aortic stenosis in Newfoundlands. The exact mechanisms of development of aortic stenosis are unknown but it is postulated that the fibrocartilaginous ring of aortic stenosis is derived from embryonic inner lining of the heart (endocardium), which persists and retains its ability to develop cartilage for some time after birth. The inheritance pattern may be more complex and involve multiple genes, 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?

With a dominant mutation, the defect can appear if a dog only has one copy of affected DNA. If one parent carries one allele, half the offspring will carry at least one copy, and if both parents carry one allele, 75% of the offspring will carry at least one copy of DNA for the disorder. However, the mode of inheritance is complicated since there may be other genes – that we do not yet know of – involved in the development of aortic stenosis. In addition, and 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.

In the future, a screening tool could be developed to test for the presence of the PICALM insertion (Stern et al 2014), which may be useful for diagnosis and to determine whether dogs have the capacity to produce affected offspring.

Prior to breeding dogs from breeds predisposed to congenital cardiac abnormalities, a cardiac examination by a veterinary surgeon should be made and if a heart murmur is detected then this should be investigated (though not all heart murmurs indicate significant disease). Currently, UK Newfoundlands breed clubs have an open access database of dogs screened for heart murmurs to help breeders select dogs suitable for mating ie those that are clear of severe murmurs. Since aortic stenosis is associated with a dominant trait, affected dogs should not be bred from, since there is a very high chance of puppies carrying the gene and/or becoming affected themselves. However, further research is required to determine other genes involved in the development of aortic stenosis 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

Bellumori TP, Famula TR, Bannasch DL, Belanger JM and Oberbauer AM (2013) Prevalence of inherited disorders among mixed-breed and purebred dogs: 27,254 cases (1995-2010). Journal of the American Veterinary Medical Association 242: 1549–55. doi:10.2460/javma.242.11.1549

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. doi:10.1186/s40575-015-0014-9

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. doi:10.1111/j.1748-5827.1998.tb03722.x

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

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

Oberbauer AM, Belanger JM, Bellumori T, Bannasch DL and Famula TR (2015) Ten inherited disorders in purebred dogs by functional breed groupings. Canine Genetics And Epidemiology 2: 9. doi:10.1186/s40575-015-0021-x

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. doi:10.1111/j.1939-1676.2011.0711.x

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. doi:10.1016/S0002-8703(76)80113-5

Reist-Marti SB, Dolf G, Leeb T, Kottmann S, Kietzmann S, Butenhoff K and Rieder S (2012) Genetic evidence of subaortic stenosis in the Newfoundland dog. The Veterinary Record 170: 597. doi:10.1136/vr.100019

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

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. doi:10.1007/s00439-014-1454-0

Tidholm A (1997) Retrospective study of congenital heart defects in 151 dogs. Journal of Small Animal Practice 38: 94–98. doi:10.1111/j.1748-5827.1997.tb03326.x

© UFAW 2016


Credit for main photo above:

By SKern at the German language Wikipedia [GFDL (http://www.gnu.org/copyleft/fdl.html) or CC-BY-SA-3.0  (http://creativecommons.org/licenses/by-sa/3.0/)], via Wikimedia Commons