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
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
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.
||No murmur detected.
Murmur is very difficult to hear. Requires a quiet
room, a quiet dog, a good quality stethoscope, time and patience to detect.
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:||-> ->|
Murmur is so loud, it can be heard without a
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.
40 dogs had an aortic
velocity over 1.7m/s.
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.
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
- Presence of other heart disease.
- Severity of murmur.
- Chest width.
- Density of hair coat.
- Lung noise/panting.
- Restless patient.
- Noisy room.
- Operator factors.
These factors have all made screening for
SAS problematic and so it has been difficult to establish the inheritance of the
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
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
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
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
This study has enabled Mrs. Dukes McEwan to:
- Generate breed-specific criteria for normal values in specific breeds.
- Define criteria for diagnosis of occult DCM in specific breeds.
Observe the progression of equivocal abnormalities on echo-cardiography to occult DCM and finally to overt DCM.
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
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
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?|
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?|
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.
How much exercise would you recommend for a dog with DCM?
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.
If a dog with DCM becomes stable on treatment, can the treatment be stopped?
No. Once treatment has been started, it should not be stopped.
How often should a dog with DCM be echo-Dopplered to assess progress and the need to increase medication?
Recommend rescan 3 months after initial diagnosis and then 6 monthly to assess when to start treatment with ACE inhibitors.