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PAPER
Serum Cardiac Troponin I concentrations in cats with anaemia – a preliminary, single-centre observational study S. M. Lalor*, D. A. Gunn-Moore*, R. Cash†, A. Foot†, N. Reed* and R. J. Mellanby* *Division of Clinical Veterinary Sciences, Royal (Dick) School of Veterinary Studies and the Roslin Institute, The University of Edinburgh, Edinburgh †Rossdale & Partners, Beaufort Cottage Laboratories, Newmarket, Suffolk CB8 8JS
OBJECTIVES: A range of cardiovascular abnormalities have been associated with anaemia. However, it remains unclear whether anaemia is associated with cardiac myocyte damage in cats. The aim of this study was to assess if cats with anaemia have an increased prevalence of cardiac myocyte damage, as assessed by serum concentrations of cardiac troponin I, compared to non-anaemic, ill cats. METHODS: Serum cardiac troponin I concentrations were measured in 18 anaemic cats and in 31 nonanaemic, ill cats with non-primary cardiac, non-renal and non-primary haematological disorders. RESULTS: The serum cardiac troponin I concentrations in the anaemic group (0·43 ng/mL) were significantly higher (P=0·0002) than in the non-anaemic ill group (0·04 ng/mL). Using a cut-off of less than 0·16 ng/mL, 12 of the 18 anaemic cats had an increased serum cardiac troponin I concentration, which was significantly higher (P=0·005) than the non-anaemic ill cats (7 of 31 cats). CLINICAL SIGNIFICANCE: Serum cardiac troponin I concentrations were higher in cats with anaemia in this study. Further studies are required to establish whether the anaemia or other confounding factors is the cause of the increased serum cardiac troponin I concentrations. Journal of Small Animal Practice (2014) 55, 320–322 DOI: 10.1111/jsap.12210 Accepted: 5 February 2014; Published online: 20 March 2014
INTRODUCTION Anaemia is a common clinical presentation in cats and can be due to a variety of different causes. Cats often present with severe chronic anaemia, which may in part be due to the short half-life of red blood cells compared to other species and a lower blood volume in cats of 6 to 8% of bodyweight (Christian 2000). Many cats are able to tolerate the anaemic state remarkably well and this may be because feline haemoglobin has a relatively low affinity for oxygen. A recent retrospective study investigating the aetiology of anaemia in 180 cats revealed that a wide range of disease processes could cause anaemia (Korman et al. 2013). These included infectious (21·7%), neoplastic (20%), metabolic (11·7%), trauma (8·3%), miscellaneous (7·8%), inflammatory (6·1%), immunemediated (6·1%), anomalous (4·4%), toxic (1·1%) or vascular (0·6%) diseases with the majority (62·2%) surviving to discharge. 320
Anaemia has been shown to cause increased left heart dimensions consistent with volume overloading as a result of haemodynamic compensatory mechanisms induced by the anaemia (Wilson et al. 2010). This is considered to be due to a combination of generalised peripheral vasodilation as a result of increased nitric oxide activity because of the decreased serum haemoglobin concentrations (Martin et al. 1986) and a reduction of blood viscosity (Fowler et al. 1975). This results in a decrease in cardiac afterload and promotes an increase in cardiac output (Fowler et al. 1975). Despite the cardiovascular changes that have been associated with anaemia, it remains unclear whether anaemia directly causes cardiac myocyte damage in cats. The measurement of serum cardiac troponin I (cTnI) concentration has been shown to be a highly sensitive and specific marker for myocardial damage and allows individuals to be non-invasively screened for cardiac myocyte damage (Adams et al. 1993). It is a highly conserved protein
Journal of Small Animal Practice
•
Vol 55
•
June 2014
•
© 2014 British Small Animal Veterinary Association
Cardiac troponin I in feline anaemia
MATERIALS AND METHODS This study was undertaken at The Royal (Dick) School of Veterinary Studies between February 2012 and March 2013. Consecutive clinical cases of cats diagnosed with anaemia, classified as a packed cell volume (PCV) less than 24%, were considered eligible for inclusion in the study. Cats were excluded from the study if they had received any blood or colloid products or more than 4 mL/kg/hour of crystalloid fluids before blood sampling. Anaemic cats with evidence of renal disease, defined as a serum creatinine concentration greater than 177 umol/L and a urine specific gravity of less than 1·035, were excluded as renal disease has been associated with an increase in serum cTnI concentrations. The non-anaemic, ill population consisted of cats with nonprimary cardiac, non-renal and non-primary haematological disorders. Cats which were not anaemic and had no evidence of cardiac or renal disease based on clinical examination, biochemistry and urinalysis were considered eligible for inclusion in the study. Total thyroxine (T4) was measured in all cats eight years or older and cats were excluded from the non-anaemic, ill group if total T4 was above the reference interval. Any cat with a murmur or arrhythmia was excluded from the non-anaemic, ill group. During clinical sampling of each case an aliquot of serum was obtained and frozen at −80°C. Once sample collection was complete, the samples were transported on dry ice for analysis. Serum cTnI was measured using an Immulite Troponin I immunometric chemiluminescent assay system (Siemens Medical Solutions Diagnostics). This assay uses a mouse monoclonal antitroponin I antibody and a goat polyclonal antitroponin I antibody for capture and detection, respectively, of troponin I molecules, directed against a unique 31 amino acid extension of the cTnI N-terminus. The lower limit of the assay in cats is 0·02 ng/mL with a stated intra-assay coefficient of variation over the concentration range of cTnI measured of 3·9%. The serum cTnI concentration and ages of cats were compared between the two groups by a Mann-Whitney U test. Fisher’s exact test was used to assess the proportion of male and female cats in each group and to compare the proportion of anaemic and non-anaemic, ill cats with a serum cTnI concentration above the reference interval. Spearman’s rank correlation test was used to investigate the relationship between the serum cTnI Journal of Small Animal Practice
•
Vol 55
•
June 2014
•
concentrations and PCV. Statistical analysis was performed with a commercial software package (GraphPad Prism 6) and P
PAPER
Serum Cardiac Troponin I concentrations in cats with anaemia – a preliminary, single-centre observational study S. M. Lalor*, D. A. Gunn-Moore*, R. Cash†, A. Foot†, N. Reed* and R. J. Mellanby* *Division of Clinical Veterinary Sciences, Royal (Dick) School of Veterinary Studies and the Roslin Institute, The University of Edinburgh, Edinburgh †Rossdale & Partners, Beaufort Cottage Laboratories, Newmarket, Suffolk CB8 8JS
OBJECTIVES: A range of cardiovascular abnormalities have been associated with anaemia. However, it remains unclear whether anaemia is associated with cardiac myocyte damage in cats. The aim of this study was to assess if cats with anaemia have an increased prevalence of cardiac myocyte damage, as assessed by serum concentrations of cardiac troponin I, compared to non-anaemic, ill cats. METHODS: Serum cardiac troponin I concentrations were measured in 18 anaemic cats and in 31 nonanaemic, ill cats with non-primary cardiac, non-renal and non-primary haematological disorders. RESULTS: The serum cardiac troponin I concentrations in the anaemic group (0·43 ng/mL) were significantly higher (P=0·0002) than in the non-anaemic ill group (0·04 ng/mL). Using a cut-off of less than 0·16 ng/mL, 12 of the 18 anaemic cats had an increased serum cardiac troponin I concentration, which was significantly higher (P=0·005) than the non-anaemic ill cats (7 of 31 cats). CLINICAL SIGNIFICANCE: Serum cardiac troponin I concentrations were higher in cats with anaemia in this study. Further studies are required to establish whether the anaemia or other confounding factors is the cause of the increased serum cardiac troponin I concentrations. Journal of Small Animal Practice (2014) 55, 320–322 DOI: 10.1111/jsap.12210 Accepted: 5 February 2014; Published online: 20 March 2014
INTRODUCTION Anaemia is a common clinical presentation in cats and can be due to a variety of different causes. Cats often present with severe chronic anaemia, which may in part be due to the short half-life of red blood cells compared to other species and a lower blood volume in cats of 6 to 8% of bodyweight (Christian 2000). Many cats are able to tolerate the anaemic state remarkably well and this may be because feline haemoglobin has a relatively low affinity for oxygen. A recent retrospective study investigating the aetiology of anaemia in 180 cats revealed that a wide range of disease processes could cause anaemia (Korman et al. 2013). These included infectious (21·7%), neoplastic (20%), metabolic (11·7%), trauma (8·3%), miscellaneous (7·8%), inflammatory (6·1%), immunemediated (6·1%), anomalous (4·4%), toxic (1·1%) or vascular (0·6%) diseases with the majority (62·2%) surviving to discharge. 320
Anaemia has been shown to cause increased left heart dimensions consistent with volume overloading as a result of haemodynamic compensatory mechanisms induced by the anaemia (Wilson et al. 2010). This is considered to be due to a combination of generalised peripheral vasodilation as a result of increased nitric oxide activity because of the decreased serum haemoglobin concentrations (Martin et al. 1986) and a reduction of blood viscosity (Fowler et al. 1975). This results in a decrease in cardiac afterload and promotes an increase in cardiac output (Fowler et al. 1975). Despite the cardiovascular changes that have been associated with anaemia, it remains unclear whether anaemia directly causes cardiac myocyte damage in cats. The measurement of serum cardiac troponin I (cTnI) concentration has been shown to be a highly sensitive and specific marker for myocardial damage and allows individuals to be non-invasively screened for cardiac myocyte damage (Adams et al. 1993). It is a highly conserved protein
Journal of Small Animal Practice
•
Vol 55
•
June 2014
•
© 2014 British Small Animal Veterinary Association
Cardiac troponin I in feline anaemia
MATERIALS AND METHODS This study was undertaken at The Royal (Dick) School of Veterinary Studies between February 2012 and March 2013. Consecutive clinical cases of cats diagnosed with anaemia, classified as a packed cell volume (PCV) less than 24%, were considered eligible for inclusion in the study. Cats were excluded from the study if they had received any blood or colloid products or more than 4 mL/kg/hour of crystalloid fluids before blood sampling. Anaemic cats with evidence of renal disease, defined as a serum creatinine concentration greater than 177 umol/L and a urine specific gravity of less than 1·035, were excluded as renal disease has been associated with an increase in serum cTnI concentrations. The non-anaemic, ill population consisted of cats with nonprimary cardiac, non-renal and non-primary haematological disorders. Cats which were not anaemic and had no evidence of cardiac or renal disease based on clinical examination, biochemistry and urinalysis were considered eligible for inclusion in the study. Total thyroxine (T4) was measured in all cats eight years or older and cats were excluded from the non-anaemic, ill group if total T4 was above the reference interval. Any cat with a murmur or arrhythmia was excluded from the non-anaemic, ill group. During clinical sampling of each case an aliquot of serum was obtained and frozen at −80°C. Once sample collection was complete, the samples were transported on dry ice for analysis. Serum cTnI was measured using an Immulite Troponin I immunometric chemiluminescent assay system (Siemens Medical Solutions Diagnostics). This assay uses a mouse monoclonal antitroponin I antibody and a goat polyclonal antitroponin I antibody for capture and detection, respectively, of troponin I molecules, directed against a unique 31 amino acid extension of the cTnI N-terminus. The lower limit of the assay in cats is 0·02 ng/mL with a stated intra-assay coefficient of variation over the concentration range of cTnI measured of 3·9%. The serum cTnI concentration and ages of cats were compared between the two groups by a Mann-Whitney U test. Fisher’s exact test was used to assess the proportion of male and female cats in each group and to compare the proportion of anaemic and non-anaemic, ill cats with a serum cTnI concentration above the reference interval. Spearman’s rank correlation test was used to investigate the relationship between the serum cTnI Journal of Small Animal Practice
•
Vol 55
•
June 2014
•
concentrations and PCV. Statistical analysis was performed with a commercial software package (GraphPad Prism 6) and P
