Untersuchungen zu NTpro-BNP bei der dilatativen Kardiomyopathie des Dobermanns

Up to now, the occult phase of the cardiomyopathy in Doberman
Pinschers, with a cumulative prevalence of 63 % in Europe (WESS et
al., 2009b), can only be diagnosed by specialized and
cost-intensive methods, such as the 24-h-ECG (Holter) and the
echocardiogram. Electrocardiographic and echocardiographic changes
usually appear at an age, in which the dogs were already used for
breeding. Considering the genetic health of the Doberman Pinscher
breed, it is of great importance to diagnose the genetically
determined cardiomyopathy before it can be passed on to the
offspring. The aim of this study Analysis of NTpro-BNP in Dilated
Cardiomyopathy of the Doberman Pinscher was to evaluate NTpro-BNP
in the Doberman Pinscher population, in healthy animals as well as
in various stages of cardiomyopathy, to define reference values and
to validate the use of NTpro-BNP as a diagnostic tool. Therefore,
250 healthy and 108 dogs with cardiomyopathy were studied between
2004 and 2008, in total 480 examinations. NTpro-BNP measurements
were performed in plasma samples, using the ELISA VETSIGNTM Canine
CardioSCREEN Ntpro-BNP, Guildhay Ltd., UK. NTpro-BNP concentrations
increased in correlation with the severity of disease. There was a
statistically significant difference between the healthy control
group (mean 315.7 pmol/l) and the occult and decompensated groups
as well as the whole dog population with cardiomyopathy. To
differentiate healthy dogs from dogs with cardiomyopathy, a cut-off
value of 413.8 pmol/l was established that provided an area under
the receiver operator curve of 0.820, with a sensitivity and
specifity of 72.4 % and 80.2 %, respectively. There was no
significant influence of age, weight or sex on the NTpro-BNP
concentration. Sensitivity reached 90.0 % for predicting abnormal
echocardiographic changes. Interestingly, there was a statistically
significant increase of NTpro-BNP in the occult group with
exclusively VPCs even before echocardiographic changes were
present. The “still normal” group, consisting of examinations of
dogs that appeared to be healthy without any measurable signs at
that time, but which later on developed cardiomyopathy, is highly
interesting. Although the mean NTpro-BNP level (499.7 pmol/l) was
higher than the mean NTpro-BNP concentration in the occult group
with exclusively VPCs, no statistically significant difference was
achieved in comparision to the healthy control group using
Bonferroni’s equitation. The small number of only 17 dogs in this
group might be a reason for the lack of statistical significance.
One limitation of this study is the fact that not all dogs,
especially those in the healthy control group, could be followed up
to the end of their lives. Therefore, it might be possible that
“still healthy” dogs with genetically determined cardiomyopathy are
included in the healthy control group. As a consequence, the
reference value could be falsely high. Long-term studies will be
needed to validate the reference value in a group of definitively
genetically healthy animals. The tendency to higher NTpro-BNP
values in the still normal group also should be studied in a larger
population in order to evaluate the potential of NTpro-BNP as an
early marker of cardiomyopathy in Doberman Pinschers. NTpro-BNP
cannot replace the Holter ECG and echocardiographic measurements in
the diagnosis of occult cardiomyopathy at present. But if the
time-consuming and cost-intensive methods that require a high
specialization are not available, NTpro-BNP levels could indicate
the necessity of referring the patient to a cardiologist. Because
of the high sensitivity of 90 % for predicting abnormal
echocardiographic changes, it might be possible that the
measurement of NTpro-BNP eventually could replace the
echocardiographic examination, but not the Holter-ECG.