Contents

1. Introduction	2. Sub-Aortic Stenosis (SAS)
3. Classification of Sub-Aortic Stenosis	4. What is a Heart Murmur?
5. Grading of Heart Murmurs	6. Diagnosis of SAS
7. Factors Influencing the Detection of Heart Murmurs	8. Patent Ductus Arteriosus (PDA)
9. Dilated Cardiomyopathy	10. Inheritance of DCM
11. Questions & Answers

1. INTRODUCTION

It is difficult to prove whether a given disease is inherited, but a familial incidence is much easier to identify. If three generations of a family are affected by a disease, then it probably is inherited. Knowledge of as many siblings as possible is necessary in order to calculate the mode of inheritance of a condition.

If a disease does not skip generations, there are affected offspring even when one parent is normal, and approximately 50% of offspring of an affected individual inherit the disease, then the condition is likely to be inherited as an autosomal dominant defect.

Dilated cardiomyopathy and sub-aortic stenosis have now both been shown to be the result of an autosomal dominant defect in Newfoundlands.

2. SUB-AORTIC STENOSIS (SAS)

The heart is basically a double pump, with two collecting chambers – the right and left atria, and two pumping chambers – the right and left ventricles. There are valves at the entrance to each atrium, at the junction between the atria and ventricles and at the exit of each ventricle. The ‘mitral’ valve lies between the left atrium and the left ventricle, the ‘tricupsid’ valve lies between the right atrium and the right ventricle, the aortic valve lies at the exit of the left ventricle and the pulmonary valve lies at the exit of the right ventricle.

The right side of the heart pumps blood through the lungs, where blood pressure is relatively low. The 'right' pump does not work as hard as the left and so the walls of the ventricle are thinner (less muscle). The left side of the heart pumps blood under high pressure throughout the body and the left ventricle is consequently thicker, with more muscle.

In Newfoundlands, sub-aortic stenosis is characterised by a ring of scar tissue below the aortic valve, which partially obstructs blood flow. The left ventricle must consequently pump harder to overcome the obstruction and the muscle wall becomes thicker. If the obstruction is very severe, the muscle becomes so thick that the blood vessels which supply it with oxygen cannot keep up with demand. This lack of oxygen in the heart muscle causes an irregular heart rhythm, which may cause fainting or sudden death.

Blood must flow through the diseased valve very quickly to overcome the obstruction. It is possible to measure the speed of blood flow across the aortic valve with an echo-Doppler machine.

3. CLASSIFICATION OF SUB-AORTIC STENOSIS (Pyle)

(This is a classification of the abnormality found in the heart, not the loudness of a murmur)

Grade 1: One or more raised nodules below the aortic valve.

This causes a very quiet murmur, or sometimes no murmur at all, but is genetically very important.

Grade 2: A narrow ridge extending around the outflow tract of the left ventricle.

Grade 3: Fibrous band encircling the outflow of the left ventricle.

In the USA most of the screening of Newfoundlands relies on listening to the heart with a stethoscope (auscultation), but this is not adequate to detect all the dogs with a Grade 1 lesion. Most of the research in the UK has been done in Boxer dogs, more than 70% of which have been found to have a murmur.

4. WHAT IS A HEART MURMUR?

A heart murmur may be defined as turbulent blood flow which can be heard circulating within the heart.

Turbulent flow occurs through narrowed valves. Whether a murmur can be heard depends on the Reynolds Factor, which is affected by:

• Raised velocity of blood flow.
• Width of blood vessel. (this is a factor in racehorses, but not in dogs).
• Density of blood.
• Reduced blood viscosity.

5. GRADING OF HEART MURMURS

The use of auscultation to grade heart murmurs is very subjective.

Grade 0/6:	No murmur detected.
Grade 1/6:	Murmur is very difficult to hear. Requires a quiet room, a quiet dog, a good quality stethoscope, time and patience to detect.
Grade 2/6:	A quiet murmur that is often very localised, but which can be detected immediately with a stethoscope.
Grade 3/6:	Murmur is progressively louder -> ->
Grade 4/6:	-> ->
Grade 5/6:	-> ->
Grade 6/6:	Murmur is so loud, it can be heard without a stethoscope.

6. DIAGNOSIS OF SAS

The most reliable way to diagnose SAS is by 'colour-flow echo Doppler; examination. This basically allows the veterinary veterinary surgeon to 'look' inside the heat using ultrasound. It allows the speed of blood flowing across the aortic valve to be measured by the Doppler technique and as blood flowing in different directions is represented with different colours, the direction of blood flow and turbulent blood flow can both be identified. Nodules lead to turbulence beneath the aortic valve and in mild/severe stenosis, there is back-flow of blood across the valve (aortic regurgitation).

Diagnosis of SAS requires one or more of:

• Peak aortic blood flow over 1.7 metres per second.
• Evidence of anatomical abnormalities with 2-dimensional ultrasound.
• Colour-flow turbulence in the left ventricular outflow tract.
• Regurgitation of blood from the aorta into the left ventricle.

Measurement of aortic blood flow requires a high degree of skill and it takes two years of specialist training to become proficient in the technique. The ultrasound beam must be absolutely parallel to the direction of blood flow (the easiest way to achieve this is with a 'subcostal view' – the ultrasound probe is held in the centre of the chest, just below the breastbone).

Some Newfoundlands without an audible murmur have been found to have a blood flow over 1.7m/s. Stress/excitement may cause increase in flow in some dogs, and so a flow of 1.7 to 2.0m/s is not absolutely diagnostic of SAS.If, however, the dog is very calm but still has a flow over 1.7m/s, then it has mild SAS.

Detection of heat murmurs in Newfoundlands can be very difficult. Some dogs with a velocity over 2.0m/s do not appear to have an audible murmur, but if they are bred from, they produce the same number of affected offspring as dogs with grade 2/6 murmurs. Inter-vet variability and inter-dog variability also occur, although the consistency of grading between vets has improved. These are just some of the problems inherent with auscultatory screens.

As part of the Kennel Club Charitable Trust Research, 165 Newfoundlands were echo-Dopplered.

1. 40 dogs had an aortic velocity over 1.7m/s.
2. Only 14 of these had an audible murmur.(10 had 1/6; 2 had 2/6; 1 had 3/6; 1 had 4/6) 26 dogs had SAS but no audible murmur.
3. In dogs with raised flow and:

   0/6 (no murmur) - the aortic flow ranged from 1.71 – 2.15m/s

   1/6 - the aortic flow ranged from 1.73 – 2.39m/s

   2/6 - the aortic flow ranged from 1.79 – 1.92m/s

   3/6 - the aortic flow was 2.24m/s

   4/6 - the aortic flow was 3.6m/s

7. FACTORS INFLUENCING THE DETECTION OF HEART MURMURS

1. Presence of other heart disease.
2. Severity of murmur.
3. Chest width.
4. Density of hair coat.
5. Lung noise/panting.
6. Restless patient.
7. Noisy room.
8. Operator factors.

These factors have all made screening for SAS problematic and so it has been difficult to establish the inheritance of the disease.

8. PATENT DUCTUS ARTERIOSUS (PDA)

This condition has been seen with increasing frequency in Newfoundlands in the USA over the last 5 years. The exact mode of inheritance is not known, but it is familial and affected individuals should not be bred from.

The ductus arteriosus is a small blood vessel that joins the pulmonary artery to the aorta in unborn puppies (it carries blood directly from the right side of the heart to the aorta because the lungs are not working – unborn puppies receive all their oxygen via the placenta).

This vessel should close automatically as the lungs inflate after birth. If it does not close, large amounts of blood are diverted from the aorta and into the lungs, without reaching the body. This gives rise to a very typical murmur.

It is important to recognise this condition as soon as possible, since it is curable with surgery. If the individual is not treated, the heart will eventually become so badly damaged that surgery will be fatal.

9. DILATED CARDIOMYOPATHY

The Kennel Club Charitable Trust funded Mrs. Dukes McEwan’s original research into this problem in several breeds. However, due to the commitment of Newfoundland owners, further research into finding a genetic marker for the condition will be carried out solely in Newfoundlands.

Dilated cardiomyopathy is a disease of the heart muscle in which the heart fails to pump correctly, causing the heart to become dilated and thin walled.

• Progressive weakening leads to damming back of blood within the circulation, thereby causing ‘heart failure’ and leading to symptoms of coughing and breathlessness.
• As the heart becomes dilated, the valves become stretched and leak, leading to the development of heart murmurs. Once the heart begins to dilate, the individual will respond less well to drug therapy.
• As the atria dilate, the electrical activity of the heart is disturbed and the heartbeat becomes erratic (atrial fibrillation). If the heart rate rises above 200 beats per minute, the outlook is very poor, so this must be brought under control with drugs.

Research involved screening relatives ofaffected dogs to try to identify early signs of disease, and following disease progression with repeated echo-Doppler examinations.

The degree of contraction of the heart muscle (called fractional shortening) is the main variable measured in the diagnosis of DCM. A reduction in fractional shortening in ‘normal’ dogs was found to be followed by slow progression to DCM over 1 – 2 years. If further research shows a reduction in fractional shortening to be an early predictor of DCM, this may form the basis of a screening test.

This study has enabled Mrs. Dukes McEwan to:

1. Generate breed-specific criteria for normal values in specific breeds.
2. Define criteria for diagnosis of occult DCM in specific breeds.
3. Observe the progression of equivocal abnormalities on echo-cardiography to occult DCM and finally to overt DCM.
4. Investigate the familial tendency of the disease – it is probably due to an autosomal dominant defect.

10. INHERITANCE OF DCM

Between 20% and 30% of people with dilated cardiomyopathy have a familial variant of the disease, however, this is probably an underestimate due to difficulties with screening. The inheritance is likely to be as an autosomal dominant, although other modes of inheritance are found in some families. In humans, affected chromosome loci have been identified by genetic linkage analysis and several different chromosomes may be involved.

In dogs it seems that a variety of genetic abnormalities can produce the same end-disease, although within a breed it is probable that only one abnormality will cause a given disease. The gene responsible for DCM may not be the same in all breeds (this is called genetic heterogeneity and occurs in human DCM too).

In the early stages of DCM, a dog may show no abnormality on auscultation, may have no x-ray evidence of disease, and may have a regular heart beat with no abnormalities on ECG. However, 2D and M-mode echo-cardiography are sensitive techniques for finding impaired cardiac function and post mortem examination of affected hearts will provide important information.

Cardiologists treat the symptoms of DCM and not its cause, when the genetic defect has been found, it will be possible to treat the cause.

Mrs. Dukes McEwan concluded by thanking the following for their support:

The Kennel Club Charitable Trust.

The British Heart Foundation.

Colleagues in Edinburgh.

The Newfoundland Club.

The Northern Newfoundland Club

The Scottish Newfoundland Club

11. QUESTIONS & ANSWERS

Q:	How is DCM Treated?
A:	The aims of treatment are to counteract fluid retention, slow the heartbeat and improve contractility. In humans ACE inhibitors (Angiotensin Converting Enzyme inhibitors e.g. enalapril = Cardiovet) have been shown to slow the progression of the disease if given early, but if given too early they can accelerate progression. Introduction of these drugs must be carefully timed. If the left atrium is enlarged, ACE inhibitors should be given. Newfoundlands tend to develop DCM at a relatively late age and progress relatively slowly. In general they respond well to treatment. (Dobes and Weimeraners progress very quickly.)
Q:	Is co-enzyme Q10 useful?
A:	Studies into the effect of Co-Q10 have not been very scientific but humans seem to survive longer and have fewer symptoms if they take Co-Q10. It will do no harm and will not interfere with other treatment. If the basic cause of DCM is failure of energy production within the heart muscle, then Co-Q10 may well help. Studies in humans have shown it takes six months to work and so should be given as early as possible.
Q:	How much exercise would you recommend for a dog with DCM?
A:	Fit muscles are better able to cope with the reduced oxygen levels seen in dogs with DCM, therefore regular exercise is advantageous once the condition is stable, but not in acute disease.
Q:	If a dog with DCM becomes stable on treatment, can the treatment be stopped?
A:	No. Once treatment has been started, it should not be stopped.
Q:	How often should a dog with DCM be echo-Dopplered to assess progress and the need to increase medication?
A:	Recommend rescan 3 months after initial diagnosis and then 6 monthly to assess when to start treatment with ACE inhibitors.