Heart disease – dilated cardiomyopathy (DCM)


DCM is a complex disease. This is a brief overview of some of the main points in connection with it.


What is DCM? What are the symptoms?

DCM is a heart condition where the wall of the left ventricle of the heart (the main pumping chamber) fails to pump normally, and so it stretches and thins (so the left ventricle dilates).  As the disease progresses, pressures build up in the heart, and then can dam back into the lungs (since oxygenated blood from the lungs flows into the left side of the heart). If the lungs fill with fluid, this is called congestive heart failure (CHF).  The enlarged heart and the fluid in the lungs together lead to shortness of breath and coughing, which progresses to severe breathing difficulties (dyspnoea).  The right side of the heart can also be affected, and if this fails, the abdomen becomes distended with fluid that has leaked out of the congested liver. 

The abnormal heart muscle can also have abnormal electrical activity, leading to irregular heartbeats (arrhythmia). These irregular beats are usually from the main pumping chambers of the heart, the ventricles, and are called ventricular premature complexes (VPCs). If there are fast runs of abnormal complexes, this is called ventricular tachycardia (VT), which can lead to fainting (syncope) or even, if the heart rhythm degenerates further, to sudden death.  Some dobermanns show the arrhythmias even before the heart itself is dilated.

There is research (1) that suggests over half of dobermanns will develop DCM at some stage in their life. If they develop it during later life, then this is not unexpected, as heart disease is a typical disease of older age in dogs as in humans. However, too many dobermanns develop DCM in earlier life. A research project of the University of Liverpool in association initially with the Dobermann Breed Council (DBC) and later with the UK Dobermann Partnership (UKDP) carried out 255 tests (see below for details of Troponin testing) and about 11% tested high. Given the average age of tested dogs of less than 4, this is quite high, even allowing for the fact that other illnesses can cause a temporary high result.

Often DCM has no symptoms in its early stage (referred to as preclinical or occult DCM), although heart testing will usually show up abnormalities such as a dilated left ventricle detected by heart ultrasound (echocardiograph) or irregularities such as arrhythmias even during this stage (detected with a 24 hour ECG recording, called a Holter monitor).

What tests can be carried out to diagnose DCM?

Tests can only determine whether there are signs of DCM at the point of testing; they cannot predict whether the dog (or its progeny) will develop DCM later in life. Because DCM can appear in later life, heart testing a young dobermann once only is not informative; the dog needs to be tested repeatedly throughout its lifetime.

Why test?

There are several reasons for testing dobermanns annually. The first is with regard to breeding. Given that the incidence of DCM is high, and that is known to be in major part genetic, it is important to ensure that dogs used for breeding are clear of any symptoms at the time. It is then important to continue testing the parents so that there is information on any later development of DCM, for instance to ensure that the progeny are not mated with others whose parents developed DCM. The other major reason is that early diagnosis and treatment can substantially prolong the life of your dobermann and control the debilitating symptoms. The PROTECT study showed that early treatment does delay progression of disease into congestive heart failure, so testing benefits the individual dog. Testing therefore should not be restricted to the breeding population. A third point is that, the more dogs are tested (provided the results are publicly available), the more information we will have to understand how the disease is passed on and which lines are most affected.

Echo/Holter

The test usually referred to as the ‘gold standard’ is a combination of echocardiography (ultrasound of the heart) and a Holter monitor, which measures heart rate and rhythm over 24 hours. The 24 hour monitoring allows the vet to assess potentially life-threatening abnormal rhythms (ventricular tachycardia: VT), which can be treated to attempt to reduce the risk of syncope (fainting) or sudden death. However, these tests are expensive and time-consuming. In addition, they only test for presence of the disease at that point in time and so need to be repeated regularly through the dog’s life.

Troponin I

Another test that is being evaluated is a blood test for a cardiac biomarker called high-sensitivity Troponin I.  Troponin I is localised in heart muscle cells. If they are damaged in DCM, Troponin I is released into the blood stream, so increased levels in a blood sample indicate presence of heart muscle cell injury.  A level of less than 0.07 ng/mL is considered normal.  A result of 0.07 or above needs further investigation. However, it is important to note that Troponin levels can also be raised temporarily in response to other illnesses that can also affect the heart muscle (such as trauma, bloat, anaemia, etc). Some research (2) several years ago found that Troponin I was effective at identifying early DCM, but not as effective as the echo/Holter combination. There is now a high-sensitivity Troponin I assay and we are evaluating whether this has a higher success rate in diagnosing DCM. This is important as it is a much cheaper test – usually less than £50. Of the 27 dogs that tested high in the early phase of our research, 6 have already died (average age 9.5) and 3-4 of those are likely to have died of DCM. This suggests the test is useful and further research is now ongoing to retest dogs and back this up with NT-pro-BNP (see below) and echo/Holter. A grant has been received from the Kennel Club Charitable Trust to fund this and further funds have been raised by member clubs of the former DBC and of the UKDP.

NT-pro-BNP

This is another biomarker. Research (3) showed that it was slightly more sensitive than Troponin I at identifying Dobermanns that really did have DCM (ie very few that have a high result, but don’t have DCM: false positives), but a higher proportion of those that tested negative went on to develop DCM (false negatives).  Thus, on its own, this test has a rather high risk of missing dogs that have incipient DCM, but combining it with high-sensitivity Troponin I may produce better results in terms of both false positives and false negatives. Evaluating this is part of the current research project. A normal test result will be less than 735 pmol/L – a result above this requires further evaluation.

Currently, the only lab in the UK running the new second generation of the NT-pro-BNP test and the high sensitivity Troponin I test is IDEXX.

Genetic testing
We are sure that DCM has a large genetic component, but this is complex and almost certainly involves a combination of a range of genes. Dr Meurs in the USA (4) carried out some research on 132 dobermanns and found that a gene called PDK4 was significant, as it was mutated in Dobermanns with DCM. Dr Meurs made clear that this was not a clear genetic marker; many dogs that had the variation on this gene would not develop DCM, and some dobermanns that did not have the variation would develop it, suggesting that there may be another cause of DCM in the breed.  It therefore had little practical use, but some breeders in the USA do ensure that they do not mate two dogs that both have the variation.  Research carried out (5) on 180 UK and German dobermanns established no significance of the PDK4 gene. Thus, this gene should not be considered to have any practical relevance to UK dobermanns.  However, a different, chromosome 5 location was significantly linked to the disease in the European and UK dobermanns (6), although there is no genetic test available for this region currently.  Although some breeders may wish to test for the PDK4 mutation, it is important to note that it should not be viewed as a reliable test, and that the other methods of testing are still required.  Importantly, it would not be correct to say or imply that a negative PDK4 genetic test has any firm implication for whether progeny will develop DCM.

Special prices for Troponin I and NT-pro-BNP testing
We have arranged special discounts for these tests with the test company IDEXX. Ask your vet to use the code TNIDB for Troponin tests. The normal fee is £34.95, plus your vet’s fee, which shouldn't really be more than £20. The discounted fee with this code is £18.72 inc VAT (plus your vet’s fee).  For NT-pro-BNP the code is BNPDB and the price is £23.04 inc VAT, again plus your vet’s fee. Please send the original or a scan of the IDEXX lab report form to Sue Thorn for adding to the master database.

How is DCM treated and what are the implications for my dobermann’s health and life expectancy?

Clinical DCM with CHF
In clinical DCM, when the dog shows signs of congestive heart failure, a combination of drugs to treat CHF and to improve heart muscle function are required. Diuretics such as furosemide are required to remove the fluid accumulations.  Drugs to counteract the hormonal activation of CHF and which accelerate the heart muscle changes include ACE inhibitors (such as benazepril, enalapril) and Spironolactone are usually indicated. Pimobendan (trade name Vetmedin) improves the heart muscle pump function and reduces the workload on the heart by dilated blood vessels. Adding this drug as part of the CHF medication has been proven to prolong life and quality of life in dobermanns with CHF due to DCM (7,8).  Once a Dobermann has CHF, the survival time, even with optimal treatment, may only be months (up to one year).

DCM with arrhythmias
If severe arrhythmias are detected during Holter monitoring, or in the dog which has collapsed (syncope) due to VT, anti-arrhythmic drugs are indicated. Sotalol is usually the drug used.

Preclinical (occult) DCM
The main treatment is a drug called pimobendan (Vetmedin).  A research project called PROTECT (9) has shown that early treatment (ie before the symptoms are visible) can prolong the asymptomatic period before the dobermann dies or shows CHF by an extra  9 months (compared with the group of dogs in the study not receiving the drug).  Based on this study, Pimobendan will shortly be licensed to treat dobermanns with preclinical DCM. There is also some evidence to indicate that ACE inhibitors (e.g. benazepril, enalapril) may also delay progression into CHF, and it is possible but not proven that both pimobendan and an ACE inhibitor delay progression even better than either drug alone.

Once preclinical DCM is diagnosed (based on echocardiography), progression into clinical DCM or CHF may be over several years. Clinical DCM is merely the ‘tip of the iceberg’. There is a long, insidious course before the symptoms are recognised. Obviously, it is important we try and keep dogs free of symptoms and attempt to lengthen this phase.

It is worth bearing in mind that no drug can cure DCM. The aim of treatment is to manage the clinical signs (symptoms) of congestive heart failure due clinical DCM, or to delay progression into CHF during the preclinical DCM phase. However, the disease is still present and will progress slowly despite treatment. 

What research is being done?

The PROTECT trial mentioned above proved the value of regular testing and early diagnosis. The main current research project in the UK is the University of Liverpool/UKDP project, which will test 100 dobermanns using high-sensitivity Troponin I, NT-pro-BNP, echocardiogram and 24 hour Holter, and will then repeat the Troponin and NT-pro-BNP tests one year later. Owners of participating dogs (which must be at least 4 years old) will contribute £150 to the costs, and the rest is funded by the Kennel Club Charitable Trust and the UKDP (including money from the former DBC). Full details and application forms can be found here [hyperlink to project details].

Results of high sensitivity Troponin I tests carried out by the University of Liverpool and UKDP

Advice for puppy purchasers

As mentioned above, although there is a genetic test for DCM, it cannot be relied on to detect all cases. Puppy purchasers should ensure that both parents have been tested by high sensitivity Troponin I, a combination of high sensitivity Troponin I and NT-pro-BNP and/or Echocardiography and Holter monitoring (the gold standard) within one year before mating, and have normal results.  Prospective purchasers should also enquire closely about the longevity and cause of death of the parents’ antecedents. If a large proportion of recent antecedents have lived to at least 10 and have been clear of any signs of DCM, then this gives a good probability of the puppies avoiding DCM – although by no means a guarantee.

Advice for breeders

Breeders should ensure that both parents have been tested by high sensitivity Troponin I, a combination of Troponin and NT-pro-BNP, and/or echo/Holter within one year before mating and have normal results. Cardiac biomarker testing should ideally be repeated annually throughout the dog’s life. We appreciate that cost and time constraints, including access to veterinary cardiologists, may mean it is not possible to repeat echo/Holter on an annual basis.  If the dog has increased cardiac biomarker results, however, it is strongly recommended that the dog’s veterinary surgeon is consulted, and the dog should ideally be referred to a cardiologist for echo/Holter. 
Breeders should keep records of test results and use these to help them decide whether their own lines, or any they use for breeding, seem likely to be affected and to modify their breeding plans accordingly. Breeders are requested to send copies of all test results to the UKDP for inclusion in the data base. Send results to Health Co-ordinator, Sue Thorn.

References

  1. Wess et al, Prevalence of Dilated Cardiomyopathy in Doberman Pinschers in various age groups (2010) J Veterinary Internal Medicine 24, 533-538

  2. Wess et al, Cardiac Troponin I in Doberman Pinschers with Cardiomyopathy (2010) J Veterinary Internal Medicine 24, 843–849

  3. Wess et al, Evaluation of N-terminal pro-B-type natriuretic peptide as a diagnostic marker of various stages of cardiomyopathy in Doberman Pinschers (2011) American J Veterinary Research 72, 642-649

  4. Meurs et al, A splice site mutation in a gene encoding for PDK4, a mitochondrial protein, is associated with the development of dilated cardiomyopathy in the Doberman pinscher(2012) Human Genetics 131, 1319–25

  5. Owcarek-Lipska et al, A 16-bp deletion in the canine PDK4 gene is not associated with dilated cardiomyopathy in a European cohort of Doberman Pinschers (2012) Animal Genetics 44, 239

  6. Mausberg et al, A locus on chromosome 5 is associated with dilated cardiomyopathy in Doberman Pinschers. (2011) PLOS One 6, e20042

  7. O'Grady et al, Effect of pimobendan on case fatality rate in Doberman Pinschers with congestive heart failure caused by dilated cardiomyopathy(2008) J Veterinary Internal Medicine 22, 897-904

  8. Fuentes et al, A double-blind, randomized, placebo-controlled study of pimobendan in dogs with dilated cardiomyopathy (2002) J Veterinary Internal Medicine 16, 255-61

  9. Summerfield et al, Efficacy of Pimobendan in the prevention of Congestive Heart Failure or sudden death in Doberman Pinschers with preclinical Dilated Cardiomyopathy (the PROTECT study) (2012) J Veterinary Internal Medicine 26, 1337-1349


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