Genetic Welfare Problems of Companion Animals

An information resource for prospective pet owners

Border Collie

Border Collie

Patent Ductus Arteriosus (POA)

Related terms: left to right shunting

Outline: The ductus arteriosus provides a short cut for blood flow in foetal animals, allowing blood from the heart to bypass the lungs, as the lungs are not functional before birth. Normally this diversion closes off at, or soon after, birth when full blood flow through the lungs is established. In some Border collie dogs, as a result of genetic faults, the ductus arteriosus remains open, leading, unless successfully treated, to the development of heart failure. The resulting progressive accumulation of fluid in the lungs causes increasing breathing difficulty, coughing, exercise intolerance and, unless euthanased, leads to death. The duration of the heart failure can be months or years and it causes progressive discomfort and distress.


Summary of Information

(for more information click on the links below)

1. Brief description

Patent ductus arteriosus (PDA) is the most common congenital, hereditary heart abnormality of dogs (Patterson 1971, Bonagura & Darke 1995, Rishniw 2004a). Border collies are predisposed to it (Patterson 1971, Bonagura & Darke 1995, Rishniw 2004a, Stafford Johnson 2006). It frequently leads to an overload of blood on the left side of the heart, which can progress to heart failure and death.

In the foetus, prior to birth, a blood vessel – the ductus arteriosus – is present providing a short cut for blood from the pulmonary artery to the aorta without going via the lungs (as these are non-functional prior to birth). This vessel should close at birth. In this disease (patent ductus arteriosus) it does not. 

The commonest reason for this failure in dogs is a hereditary lack of the smooth muscle in the vessel wall that should close it (Rishniw 2004a). When it fails to close, the result is that, during normal circulation, blood shunts from the aorta to the pulmonary artery, because the blood pressure is higher in the aorta compared with the pulmonary artery. Small shunts cause few problems (Kittleson 1998, Bonagura & Lehmkuhl 1999), but when the vessel is wide enough to allow large shunts, there is significant overload of blood flow to the left ventricle and, with time, left-sided heart failure develops.

Left-sided heart failure causes lethargy and inability to exercise, with weight loss and difficulty in breathing. There may be coughing and rapid breathing, and as the disease progresses, dogs show marked signs of respiratory distress, and may collapse or die suddenly. Most have to be euthanased due to respiratory distress at some stage.

PDA is usually treatable and, in most cases, curable if identification and intervention occur early.

2. Intensity of welfare impact             

Except in mild cases, in which there may be no welfare consequences, this disease causes left side heart failure. This leads to fluid accumulation in the lungs which makes breathing difficult. Affected dogs are likely to feel unwell and be unable to exercise normally.

As heart failure progresses and the pulmonary fluid accumulates further, breathing becomes an increasing struggle, which is likely to cause severe distress and discomfort and, unless euthanased, the dog effectively dies from drowning in its own body fluids.

Diagnostic and therapeutic procedures may have some adverse welfare effects in some dogs. 

3. Duration of welfare impact

The defect is present from the time of birth and some puppies show signs of heart failure when as young as eight weeks of age (Stafford Johnson 2006). A large proportion of affected dogs (64%) die within a year of diagnosis (Eyster et al 1976). The time course of the disease, and the period when welfare is affected, tends therefore to be occur over months to years.

4. Number of animals affected

Although Border collies are predisposed to PDA (Patterson 1971, Bonagura & Darke 1995, Rishniw 2004a, Stafford Johnson 2006) and it is seen “relatively commonly” within the breed (Stafford Johnson 2006) we are unaware of data on the proportion of collies that are affected by PDA.

Patent ductus arteriosus (PDA) is stated, by some, to be the most common congenital (present at birth), hereditary heart abnormality of dogs, accounting for 25 to 30% of these cases (Patterson 1971, Buchanan 1999, Slater 2003, Rishniw 2004a).

5. Diagnosis

Detection of a continuous, “machinery” heart murmur in any young dog is highly likely to indicate PDA (Stafford Johnson 2006, Brownlie et al 2010). Confirmation is usually made using colour-flow Doppler ultrasonography.

6. Genetics

PDA has been shown to be a polygenic threshold trait in poodles (Patterson et al 1971) and it is likely that it is inherited in this way in other predisposed breeds (Patterson 1989, Bonagura & Darke 1995). That is, it is thought that multiple genes are involved in the disease and that the severity of the defect and the disease consequences seems to be directly related to the abnormal genetic burden in each individual (Patterson 1989; Rishniw 2004a).

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

Most affected individuals can be detected early in life by listening to the heart (auscultation) with a stethoscope during veterinary examination. All puppies should have a veterinary examination prior to purchase. It is not known whether animals can carry the genes that cause the condition without developing the disease themselves, although this seems likely, and there is no way to detect such carriers at present.

8. Methods and prospects for elimination of the problem

As far as we are aware, there are no breeding programmes aimed at reducing the prevalence or eradicating PDA from the Border collie breed.

Bell (2010) suggests the assignation and use of breeding values when tackling suspected polygenetic disorders, which take account also of the prevalence of the disease in close relatives. In developing breeding strategies to tackle particular genetic diseases it is important to take account of others also and to avoid further inbreeding that might result in new genetic risks (eg where necessary, by crossing with other breeds).

 

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


1. Clinical and pathological effects

Patent ductus arteriosus (PDA) is the most common congenital , hereditary heart abnormality of dogs (Patterson 1971, Bonagura & Darke 1995, Rishniw 2004a). Border collies are predisposed to it. It frequently leads to an excessive volume of blood entering the left side of the heart causing an overload, which can progress to heart failure and death.

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 muscular walls. Between the atria and the ventricles are valves that prevent blood flowing backwards. On contraction, blood flows from the ventricles into the major blood vessels. There are also valves at the junction of the ventricles and the major arteries which prevent backward flow.

The right side of the heart receives blood from the whole of the body other than the lungs, via the vena cava. The blood accumulates in the right atrium and during a heart beat it flows past the tricuspid valve into the right ventricle and then as the right ventricle contracts (squeezes) it is pushed through the pulmonary valves into the pulmonary arteries and on to the lungs to take up oxygen.

The left side of the heart receives this oxygenated blood back from the lungs, via the pulmonary veins. The blood accumulates in the left atrium and during a heart beat it flows past the mitral valve into the left ventricle. Then, as the left ventricle contracts, the oxygenated blood is pushed through the aortic valves into the aorta and on into other major arteries which convey 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.

The phase when the heart contracts and squeezes forwards the blood it contains inside its chambers is called systole. The phase between heart beats when the heart relaxes and fills with blood returning from the rest of the body is called diastole.

Prior to birth, the circulation of the blood differs slightly from that described above because the developing foetus receives oxygen not from its lungs but from the mother via the placental blood. As the lungs are non-functional at this stage of its life, they are in an un-inflated, collapsed state and resistance to blood flow in the pulmonary arteries, that carry blood to them, is high because of this. As high levels of blood flow through the lungs is not needed, blood entering the pulmonary artery, from the left side of the heart, is diverted through a vessel – the ductus arteriosus - which provides a short cut to the aorta, the main artery that carries oxygenated blood to the tissues of the body, avoiding the lungs. 

Normally at birth, the lungs inflate and the pulmonary arterial resistance drops rapidly allowing an increase in blood flow to the lungs as they expand. During this process the muscular wall of the ductus arteriosus contracts and usually stops blood flow through the tube within 72 hours of birth (Rishniw 2004a). Then, over the next weeks the redundant tube seals off permanently and transforms into a residual fibrous tag called the ligamentum arteriosum (Rishniw 2004a). With the closing of the ductus arteriosus, the pulmonary and systemic blood circulatory systems – flow to the lungs and body respectively - are separated and the heart can function as is normal for an adult mammal.

A PDA occurs if the blood vessel fails to close at, or soon after, birth. The most common reason for this in dogs is a hereditary lack of the smooth muscle within the vessel wall, that is necessary for it to constrict shut (Rishniw 2004a). If the vessel fails to close, because the blood pressure is higher in the aorta than in the pulmonary artery after birth, blood shunts from the aorta to the pulmonary artery with each beat of the heart. Small shunts cause few problems (Kittleson 1998, Bonagura & Lehmkuhl 1999), but when the vessel is wide enough to allow large shunts, there is significant blood volume overload of the left ventricle.

As a result, the left atrial and ventricular muscle walls thicken (hypertrophy) as they have to work harder to pump the same volume of blood forward to the body. As mild heart disease progresses to moderate heart disease, the left atrium enlarges as it stretches to cope with a larger volume of blood returning from the lungs.

The heart is a complex organ and these anatomical changes lead to various ‘knock on’ problems as the body tries to compensate for the disease. At some stage these compensatory mechanisms and the shunt together prevent the heart from functioning normally and heart failure begins to develop.  The speed of development of heart failure is usually dependant on the size of the shunt (the bore of the ductus arteriosus). It should be noted that not all individuals with PDA progress to heart failure; however, most do and severe chronic heart failure (CHF) develops. The problems that an affected individual may suffer from include:

  • Pulmonary oedema: with marked left atrial enlargement and shunting of blood from aorta to pulmonary artery, the heart fails to pump sufficient blood forwards. The body detects this and the group of hormones of the renin - angiotensin – aldosterone (RAAS) system is activated which leads to retention of fluids within the body. This, and the stimulation of stress hormones, increases blood pressure, especially when the heart should be relaxing (ie increased diastolic pressures) which adds to back-pressure on the venous system. The increased diastolic pressures, increased pressure within the venous system and systemic fluid retention then leads to fluid accumulation in the lungs: an eventuality called pulmonary oedema.

    Clinical signs of pulmonary oedema include coughing, rapid breathing (tachypnea) or difficult breathing (dyspnea).

    When the excess fluid within the lung tissue sufficiently impairs oxygen exchange the animal’s mucous membrane colour, in the mouth and elsewhere, will appear blue-tinged (cyanosis). This indicates severe pulmonary oedema. At this stage dogs will have severe difficulty breathing, indicated by mouth breathing and adoption of a posture in which the affected animal holds their elbows held away from the chest.

    The increased sympathetic nervous system and stress hormone stimulation also leads to an increased heart rate (tachycardia). 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 time that the ventricles have to relax and fill with blood (diastole), as there is now less time between each contraction. Increasing heart rate can cause backward heart failure and pulmonary oedema. Eventually, the amount of blood that the heart can push forwards around the body also decreases.

    Dogs with left-sided heart failure are lethargic, intolerant of exercise and often restless at night; they may show weight loss and anorexia (not eating) (Hall et al 2003).
  • Heart arrhythmias may develop if the coordination of the heart beat becomes disrupted and myocardial failure (failure of the heart muscle to function properly) may occur as the disease progresses. Mitral valve regurgitation (leakage) may occur secondary to left ventricular dilatation (an increase in the size of the chamber of the left ventricle [Bonagura & Darke 1995]).
  • Syncope (sudden collapse and fainting) can occur in some cases of chronic heart failure. This is probably due to a failure to pump enough blood forward to the brain (Hall et al 2003).
  • Sudden death can occur with chronic left-sided heart failure (Hall et al 2003).

Dogs with a PDA, but without heart failure, will very likely appear normal to their owners and will not have any apparent welfare problems at that time. An owner might be able to detect an abnormally strong heart beat if feeling their dog’s chest. Examination with a stethoscope often reveals a heart murmur and this is commonly the way in which the disease is first detected when puppies are taken for their first vaccinations or check up. Murmurs are caused by abnormally turbulent blood flow. With PDA the murmur is a very characteristic, continuous type called a “machinery” murmur which is heard best with the stethoscope positioned in the left axila (arm pit) (Hall et al 2003, Brooks 2006, Brownlie et al 2010).

Female dogs are about three times more likely to have a PDA than males (Patterson 1971, Van Israël et al 2002, Hall et al 2003, Oliveira et al 2011). Why this is the case is not understood.

Most authors suggest that, without treatment, nearly all dogs with PDA rapidly deteriorate into heart failure and that few survive well into maturity without heart failure (Patterson et al 1971; Kittleson 1998; Hall et al 2003; Stafford Johnson 2006). Eyster et al (1976) found that 64% of affected dogs died within one year of examination. However, Van Israël et al (2002) found a greater proportion of adult dogs with PDA but without overt signs of heart failure. This may have been because of their sample being biased in that those with heart failure had died or had not been referred (Van Israël et al 2002).

Various treatments are available to close the abnormal vessel including chest surgery to ligate it (tie it off), or interventional catheterisation closure, in which a catheter is put into a peripheral artery and threaded through to the ductus arteriosus for placement of devices to block it off (eg coils, Nit occluders, or Amplatzer occluders depending on the size of the shunt [Stafford Johnson 2006]). The latter procedure is far less invasive than chest surgery. Dogs in heart failure will need medication and to be stabilised, if possible, prior to any treatment to close the vessel (Stafford Johnson 2006).

Surgical treatment can cure young animals that do not have heart failure; however, the prognosisis worse for older animals that already have a dilated right atrium, or animals with heart failure (Bureau et al 2005). Interventional catheterisation closure can also result in a cure. However, both of these methods can have unwanted complications in some cases. To avoid deterioration into heart failure, Stafford Johnson (2006) suggested that, if tests indicate that rapid deterioration or signs of heart failure are apparent, puppies may need to be treated at as young as eight to ten weeks of age.

Rarely, the shunting of blood occurs from right to left, from the pulmonary artery to the aorta. This occurs when the blood pressure in the pulmonary artery is higher than normal and greater than that in the aorta (Rishniw 2004b). Why this happens is not fully understood; however, these reverse shunts cause right ventricular hypertrophy and systemic hypoxemia (a lack of oxygenated blood flow to most of the body). Because of the location at which the arteries to the front of the body branch off from the aorta relative to the position of the PDA, usually, in these cases, the head and front limbs get sufficient oxygen but the rest of the body does not (Rishniw 2004b). Clinical signs of a reverse shunt include shortness of breath, pelvic limb weakness or collapse, seizures and differential cyanosis (with the mucous membranes in the head being pink and mucous membrane in the rear of the animal being cyanotic (blue-tinged) (Bonagura & Darke 1995). In response to insufficient oxygen, the kidneys produce hormones which stimulate excessive production of red blood cells (polycytaemia) which can thicken the blood and create secondary problems. These rare cases do not have the characteristic murmur, and require different treatment (medical only). Affected dogs often die suddenly at about three to four years of age. Six out of 237 cases of PDA in the study by Oliveira et al (2011) study were right to left shunts. Most of this document is concerned with PDAs with left to right shunts because reverse shunts are so rare.

PDA can also occur concurrently with other heart defects. In the study by Oliveira et al (2011), a second heart defect was found in just over 9% of cases of PDA (most commonly atrial septal defects, in which there is a hole connecting the left and right atria [http://www.vet.cam.ac.uk/idid/detail.php?record=470 2011]).

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2. Intensity of welfare impact

Border collies with PDA may have a period of subclinical disease during which there are no (or only slight) welfare problems, but congestive heart failure may start to develop in puppies as young as eight weeks of age (Stafford Johnson 2006). How quickly the disease develops varies, partly depending on the size of the shunt (the bore/diameter of the ductus arteriosus). Left-sided heart failure leads to fluid accumulation in the lungs which makes breathing difficult. It also causes the dog to lack energy, feel unwell and be unable to exercise properly and so significantly affect its quality of life.

As the disease progresses and there is further fluid accumulation in the lungs, breathing becomes an increasing effort, and this is likely to cause severe distress and discomfort. The condition progressively becomes worse until, unless euthanased, the dog effectively dies from drowning in its own body fluids.

Dysrhythmias may contribute to congestive heart failure occurring and the welfare implication described above. They also directly cause welfare problems by making the dog feel ill, faint or collapse.

Diagnostic and therapeutic procedures to address the condition may have some adverse welfare effects in some dogs. 

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3. Duration of welfare impact

The defect is present from the time of birth and some puppies show signs of heart failure when as young as eight weeks of age (Stafford Johnson 2006). A large proportion of affected dogs (64%) die within a year of diagnosis (Eyster et al 1976). The time course of the disease, and the period when welfare is affected, tends therefore to occur over months to years.Return to top

4. Number of animals affected

Although Border collies are predisposed to PDA (Patterson 1971, Bonagura & Darke 1995, Rishniw 2004a, Stafford Johnson 2006), and it is seen “relatively commonly” within the breed (Stafford Johnson 2006) we are unaware of data on the proportion of collies that are affected by PDA.

Patent ductus arteriosus (PDA) is stated, by some, to be the most common congenital, hereditary heart abnormality of dogs, accounting for 25 to 30% of these cases (Patterson 1971, Buchanan 1999, Slater 2003, Rishniw 2004a). Oliveira et al (2011) found it to account for 20% of congenital heart disease in their study and suggested its prevalence is higher in the USA than in Europe.

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5. Diagnosis

Detection of a continuous, “machinery” heart murmur in any young dog is almost pathognomonic (ie a direct indicative sign) for a PDA, particularly in the Maltese breed, and is highly likely to indicate its presence (Stafford Johnson 2006, Brownlie et al 2010). Confirmation is usually made using colour-flow Doppler ultrasonography.

In dogs with heart failure other diagnostic tests, including information from a full physical examination, ECG (electrocardiogram) and possibly chest and abdominal radiographs (x-rays) may be used to rule out other possible causes and to assess the stage of disease and plan treatment options.

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6. Genetics

PDA has been shown to be a polygenic threshold trait in poodles (Patterson et al 1971) and it is likely that it is inherited in this way in other predisposed breeds (Patterson 1989, Bonagura & Darke 1995). That is, it is thought that multiple genes are involved in the disease and that the severity of the defect and the disease consequences seems to be directly related to the abnormal genetic burden in each individual (Patterson 1989, Rishniw 2004a).

The genes involved have not been identified and it is not known why females are more at risk than males.

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

Most affected individuals can be detected early in life by listening to the heart (auscultation) with a stethoscope during veterinary examination. All puppies should have a veterinary examination prior to purchase. It is not known whether animals can carry the genes that cause the condition without developing the disease themselves, although this seems likely, and there is no way to detect such carriers at present.

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8. Methods and prospects for elimination of the problem

As far as we are aware, there are no breeding programmes aimed at reducing the prevalence of, or eradicating, PDA from the Border collie breed.

In tackling suspected polygenic disorders, Bell (2010) suggested the assignment and use of estimated breeding values (EBV) when determining which animals to use for breeding.  An EBV is a “numerical prediction of the relative genetic value of a particular dog” based on pedigree, health status and physical characteristics of the dog itself and of its relatives. Healthy individuals with healthy relatives have the greatest chance of carrying a low genetic load for the condition (Bell 2010). This EBV approach can also be used to try and eliminate several hereditary diseases within a breed simultaneously.

This approach (using EBVs) has proved successful in tackling some other conditions e.g. in the reduction of epilepsy in the Belgian Tervuren (Oberbauer 2005) and may be a promising way to eliminate PDA from the Border collie, although it may take many generations. Creating an extensive resource with information on all individuals within the breed and breeding values would involve extensive goodwill and compliance within the collie breeding community, breed associations and canine governing bodies which may be difficult to achieve. 

As with other polygenic disorders progress in eliminating this condition would be facilitated by determination of the genes involved and the development of tests for the detection of these.

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9. Acknowledgements

UFAW is grateful to Rosie Godfrey BVetMed MRCVS and David Godfrey BVetMed FRCVS for their work in compiling this section

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10. References

Bell JS (2010) Genetic Testing and Genetic Counseling in Pet and Breeding Dogs. World Small Animal Veterinary Association World Congress Proceedings

Bonagura JD and Darke P (1995) Congenital Heart Disease In Ettinger SJ & Feldman EC eds Textbook of Veterinary Internal Medicine 4th Ed p892-943. WB Saunders: Philadelphia, USA

Bonagura JD and Lehmkuhl LB (1999) Congenital heart disease. Textbook of Canine and Feline Cardiology; Principles and Clinical Practice, 2nd ed. WB Saunders: Philadelphia, USA pp. 471-535

Brooks W (2006) Patent Ductus Arteriosus. On-line client information sheet http://www.vin.com/Members/SearchDB/vp/vpa02437.htm Accessed 13.4.11

Brownlie S, Rishniw M and Oyama M (2010) Patent ductus arteriosus. On-line Vetstream Canis http://www.vetstream.com/canis/Content/Disease/dis00907. Accessed 13.4.11

Buchanan JW (1999) Prevalence of cardiovascular disorders. In Fox PR, Sisson DD, Moise NS, eds. Textbook of Canine and Feline Cardiology, 2nd ed. WB Saunders: Philadelphia, USA pp 458–463

Bureau S, Monnet E and Orton EC (2005) Evaluation of survival rate and prognostic indicators for surgical treatment of left-to-right patent ductus arteriosus in dogs: 52 cases (1995-2003). Journal of American Veterinary Medical Association 227: 1794-9

Eyster GE, Eyster JT, Cords BC and Johnston J (1976) Patent ductus arteriosus in the dog: Characteristics of occurrence and results of surgery in one hundred consecutive cases. Journal of the American Veterinary Medical Association 168: 435-438

Hall EJ, Murphy KF and Darke PGG (2003) Patent ductus arteriosus. In: Notes on Canine Internal Medicine pp 219-221. Blackwell Publishing: Oxford, UK

Kittleson MD (1998) Patent ductus arteriosus. Small Animal Cardiovascular Medicine Mosby: St Louis, USA pp. 218-230

Oberbauer A (2005) Recent Progress on the Genetics of Canine Epilepsy and Addison's Disease. Tufts' Canine and Feline Breeding and Genetics Conference, 2005

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(3): 477-483

Patterson DF (1971) Canine congenital heart disease: epidemiology and etiological hypotheses. Journal of small Animal Practice 12: 263-287

Patterson DF, Pyle RL, Buchanan JW, Trautvetter E and Abt DA (1971) Hereditary patent ductus arteriosus and its sequelae in the dog. Circulation Research 29: 1-13

Patterson DF (1989) Hereditary congenital heart defects in dogs. Journal of Small Animal Practice 30: 153-165

Rishniw M (2004a) Patent Ductus Arteriosus (left to right). VIN Associate. http://www.vin.com/Members/Associate/Associate.plx?DiseaseId=1325. Accessed 13.4.11.

Rishniw M (2004b) Patent Ductus Arteriosus (right to left). VIN Associate. http://www.vin.com/Members/Associate/Associate.plx?DiseaseId=39. Accessed 13.4.11

Slater D (2003) Textbook of Small Animal Surgery. Saunders: Philadelphia, USA pp 957

Stafford Johnson M (2006) Decision making in suspected congenital heart disease in dogs and cats. In Practice 28: 538-543

Van Israël N, French AT, Dukes-McEwan J and Corcoran BM (2002) Review of left-to-right shunting patent ductus arteriosus and short term outcome in 98 dogs. Journal of Small Animal Practice 43: 395–400

http://www.vet.cam.ac.uk/idid/detail.php?record=470. Accessed 14.4.11

© UFAW 2011


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