Trinity Doberman Pinschers
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Dialated Cardiomyopathy (DCM)
Additional Research identifying other Bio-Markers
Associated with Dobermans and DCM

  

                          DCM Research Updates

USA NT-proBNp Bio-marker

Why they did it - Since Occult Dilated Cardiomyopathy (ODCM) is common in Doberman Pinschers, these researchers were out to find a marker to help identify the condition as early as possible.

What they did - Using a combination of echocardiography, 24-hour Holter monitoring, and the NT-proBNP assay, researchers evaluated 155 asymptomatic Doberman Pinschers for the presence of ODCM. ODCM was diagnosed based on a left ventricular internal dimension (LVID) between 38.8 mm to 43 mm normalized to weight in dogs weighing up to 55 kg, the presence of > 50 ventricular premature complexes, or both.

What they found - ODCM was diagnosed in nearly half (47%) of the Doberman pinshcers evaluated based on Holter monitor readings (31), echocardiographic evidence (17), or both criteria (25). An NT-proBNP concentration > 457 pmol/L successfully identified 45.2%, 76.5%, and 96% of these patients, respectively, with ODCM. The overall sensitivity and specificity of the combination Holter monitoring and pro-BNP test to detect ODCM was 94.5% and 87.8%, respectively, with an accuracy of 91%.

Disease status and NT-proBNP concentration were independently predictive of all-cause mortality. The median survival time of dogs with > 50 ventricular premature complexes (469 days), NT-proBNP concentration > 900 pmol/L (284 days), or ODCM (474 days) was significantly (P < 0.0001) shorter than those with < 50 ventricular premature complexes (1,743 days), NT-proBNP concentration < 900 pmol/L (1,743 days), or those without disease (1,743 days).

Take-home message - Use of the NT-proBNP assay in conjunction with a Holter monitor is the most accurate way to predict ODCM in Doberman Pinschers. An elevated NT-proBNP concentration, > 50 ventricular premature complexes during Holter monitoring, or both indicate a greater than sevenfold likelihood for the presence of ODCM. An elevation in the NT-proBNP concentration in this breed would support the need for further testing such as echocardiography to evaluate for ODCM.

Singletary GE, Morris NA, O’Sullivan ML, et al. Prospective evaluation of NT-proBNP assay to detect occult dilated cardiomyopathy and predict survival in Doberman Pinschers. J Vet Intern Med 2012;26(6):1330-1336.

Link to abstract: http://onlinelibrary.wiley.com/doi/10.1111/j.1939-1676.2012.1000.x/abstract

http://veterinarymedicine.dvm360.com/vetmed/Medicine/Journal-Scan-Utility-of-NT-proBNP-assay-to-detect-/ArticleStandard/Article/detail/801774


UK Dobermann Cardiac Biomarker - TROPONIN I (cTnI) Testing Scheme

There is a study analyzing blood tests results of a cardiac biomarker, being studied in the UK which has promise of being the most predictive of individual dogs pre-disposition to acquire DCM.

An important update!! Bitten Jönsson (Doberman breeder of many years) has conducted research and proposed a test that has now been adopted by the The Dobermann Breed Council in the UK as a diagnostic test with regard to DCM. This test measures lactate levels in Dobermanns and offers a high probability answer as to whether the dogs is most likely to develop DCM or not. The test is recommended to be conducted at 12 months of age, which is perfect for breeders to adopt as 'Best Practice' in their breeding programs. Tthis test is available for everyone in the UK through The Dobermann Breed Council. Everyone is encouraged to send blood samples to The Dobermann Breed Council and read more about this testing and study here:

http://www.dobermannbreedcouncil.co.uk/troponin.html


This proposed test has been accepted for further research, and the testing/research study which now has started in the UK, consists of 2 blood tests - both these tests are being supported by the Dobermann Breeding Council in the UK. The test results from these tests will be compared within the study group and also analyzed against the ongoing factual clinical results which the study will produce.

The UK is the first place testing will be conducted. After evaluation of the UK test results, if they are in accordance to the estimations and projections made through the proposed paper, testing will be officially available, and the paper will be presented for review and published. All testing will be supervised by the University of Liverpool / Dr. Joanne Dukes-McEwan - professor in cardiology. This is just the beginning of the testing we are hopeful the results will prove beneficial.

In the UK Dobermanns, it was proposed that a high sensitivity cardiac Troponin I assay will identify dogs in which other investigations such as echocardiography and Holter monitoring or other health checks should be carried out. Troponin I testing should be repeated annually.

ADVICE BASED ON THE HIGH SENSITIVITY CARDIAC TROPONIN I RESULTS

NORMAL VALUE      <0.2 ng/mL    Likely to be a normal dog at the time of sampling. However, this does not mean that the dog does not have early DCM and false negative results are possible. If any exercise intolerance, coughing, shortness of breath or fainting are seen, then your veterinary surgeon should be consulted

INCREASED LEVEL    >0.2ng/mL     An increased cTnI level can be associated with heart disease such as DCM, so that other investigations such as echocardiography or Holter monitoring are strongly recommended. Please consult with your veterinary surgeon. cTnI can also be increased with other illness, which may also affect the heart muscle.

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So far 3 GENE mutations or variations have been identified on 3 different chromosomes - [Chromosome #5 (WESS-Germany) - Chromosome #8(O’Grady-USA) – Chromosome #14 (Meurs-USA)] - this confirms what has been conjectured in the past- that this disease is most likely to be polygenic in origin.

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O’Grady - Dobermann DCM from group of University of Guelph-C

 

(http://avmajournals.avma.org/doi/abs/10.2460/ajvr.72.7.932 )

A new investigation of the genes associated with Dobermann DCM from group of University of Guelph-Canada, published July-2011,
http://avmajournals.avma.org/doi/abs/10.2460/ajvr.72.7.932 show that an alpha-actinin gene variant, resulted in an amino acid change in the rod-forming triple coiled-coil domain, was detected in 40% of affected Dobermann (2/5) and may contribute to the development of DCM given its potential effect on the structure of this protein.

 Alpha-actinin gene (ACTN1) is located in canine Chromosome 8. Alpha-actinin is a cytoskeletal protein that in muscle cells is found at the Z-disk of sarcomeres where they help anchor the myofibrillar actin filaments.

This research illustrates newly the polygenic and complex nature of DCM in Dobermann
Reference:  O’Sullivan ML, O’Grady MR, Pyle WG, Dawson JF (2011). Evaluation of 10 genes encoding cardiac proteins in Doberman Pinschers with dilated cardiomyopathy. Am J Vet Res.;72(7):932-9.

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Dr. Gerhard Wess - Germany
A Locus on Chromosome 5 Is Associated with Dilated Cardiomyopathy in Doberman Pinschers

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3098859/

Recently, Dr. Gerhard Wess of Ludwig Maximilians University (Munich) has published a biochemical immunoassay for DCM. Cardiac Troponin I (cTnI) is a polypeptide involved in myocardial contraction that inhibiting skeletal proteins actin-myosin interaction in cardiomyocytes, and has been shown to be a highly sensitive biomarker of myocardial injury and evaluation of DCM risk in DobermannSo far 15 genes (ACTC1, CAV1, CSRP3, DES, LDB3, LMNA, MYH7, PLN, SGCD, TCAP, TNNC1, TNNI3, TNNT2, TPM1, VCL) were studied, but did not reveal the causative mutation for Doberman DCM [17][22]. Wess detected a genome-wide significant association on canine chromosome 5 amongst the study group.  Wess’s findings were that approximately half of the DCM affected Doberman Pinschers in his study  carried the risk-allele on CFA 5 and indicates that this is a major, but not the only genetic risk factor for DCM in this breed.  In UK Dobermanns, we therefore propose that high sensitivity cardiac Troponin I assay will identify dogs in which other investigations such as echocardiography and Holter monitoring or other health checks should be carried out. Troponin I testing should be repeated annually.

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DCM 1 and DCM 2 Gene Mutation Discoveries

Dr Meurs
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There is to date only 2 genetic DCM DNA tests for the,many suspected gene mutations associated with Heart Disease.  This first mutation, DCM1 PDK4 is located on chromosome 14, this test is commercially available through the University of North Carolina.

Dr Meurs has found another genetic mutation DCM2 - However she has not produced any of her research for peer review.  Since we have no idea how many dobermans were used in her research, nor how many of them tested Normal (0 copies of the gene mutation), Heterozygous (1 copy of the gene mutation) or Homozygous (2 copies of the gene) its hard to place a value on this discovery.  Dr Muers has also not published where, what chromosome this mutation was found.

As time goes by from the first DCM1 mutation and now the 2nd, I find that the initial test results and their meaning or correlation to predicting heart disease has less value. Dr Meurs has not done any follow up on any of the dogs tested in the 3 result categories. NONE and she has no plans to follow up on any of the dogs tested.

This makes the initial test results almost meaningless, as we know being diagnostically clear of  DCM at the time of the test is no guarantee that the doberman will remain free of the disease or will not eventually die of the disease.  The percentages of each dobe tested in each result category will also change over time.  More Negative dogs will surely end up acuiring DCM, and more and more Hetero and Homo dogs will end up dying of something else and living to old age. So you see how important it is, to track the dogs tested and up date their health status is to putting the health results into perspective and have better information to judge just how reliable the tests results are in predicting future health - and certainly how much weight should be used when making breeding decisions

For me personally I won't even order the DCM2 test for any of my dogs until Dr Meurs publishes her research for peer review.

http://www.cvm.ncsu.edu/vhc/csds/vcgl/dobe-dc.html

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