K. Borgeat
Measurement of N-terminal pro-B type natriuretic peptide (NTproBNP) and cardiac troponin I (cTnI) has now become commonplace in general and referral practices. These assays offer a straightforward and accessible test, which are often featured in the diagnostic investigation of feline cardiac disease by veterinarians in general and referral practice alike. However, our understanding of the clinical utility of these laboratory tests is ever evolving as more research in the area is published.
Table 1 highlights common clinical scenarios in which cardiac biomarkers may be measured, and briefly summarises the evidence behind the noted utility.
Table 1
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Clinical context
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Cardiac troponin I (cTnI)
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NTproBNP
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Level of evidence
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Respiratory distress: determining cardiac from noncardiac causes.
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Higher cTnI in cardiac disease, but significant overlap between groups limits clinical use.
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Higher NTproBNP in cardiac disease. Plasma: cut-off value around 200 pmol/L may be useful, sensitivity > 85%, specificity 84–88%.
Pleural fluid can also be used; apparently more sensitively than plasma and negating requirement for a blood sample.
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High for both, NTproBNP more accurate.
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Identification of cats with occult cardiomyopathy.
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No specific studies; reported increase in cTnI for cats with subclinical heart disease.
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Higher NTproBNP in cats with subclinical cardiomyopathy. Cut-off value around 100 pmol/L appears useful.
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Higher for NTproBNP.
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Higher concentrations associated with more severe disease, but insensitive for determining which cats have mild disease.
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A patient-side test with a cut-off at this level (“abnormal” result > 100 pmol/L) has been validated in a screening population to determine cats with moderate to severe heart disease, likely to be clinically significant, but the test has not yet been validated in a general practice population of older, non-pedigree cats.
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Prognostic use in cardiomyopathy.
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Higher cTnI in cats that dies because of cardiac disease vs. noncardiac death.
cTnI > 0.7 ng/ml associated with a shorter survival time in HCM, independent of clinical size or left atrial size, possibly reflecting severe ischaemia or infarction.
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Higher single NTproBNP measurement associated with reduced survival, but not useful once presence of clinical signs or left atrial size are considered.
Reduced NTproBNP during hospitalisation (serial measurements; admit and discharge) was associated with a longer survival time than cats where NTproBNP did not reduce significantly.
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High for both.
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Hyperthyroidism.
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cTnI increased in the hyperthyroid state, to the same levels as cats with heart disease. Normalises once euthyroid state achieved by radioactive iodine therapy.
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NTproBNP increased in the hyperthyroid state, to the same levels as cats with heart disease.
Normalises once euthyroid state achieved by radioactive iodine therapy.
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High for both.
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Chronic kidney disease.
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cTnI higher in cats with azotaemic CKD than healthy age-matched controls. No correlation between creatinine and cTnI.
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Higher NTproBNP in cats with IRIS stage IV renal disease, but no correlation with creatinine concentration overall.
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High.
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Systemic hypertension.
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Increased cTnI in cats with hypertension secondary to CKD—higher still in cats with evidence of hypertensive retinopathy. However, no significant reduction with successful antihypertensive treatment and few cats underwent echocardiography.
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NTproBNP increased in cats with hypertensive retinopathy than healthy controls. Few echocardiographic results available, so incidental cardiomyopathy cannot be excluded.
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Medium.
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Anaemia.
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Increased cTnI in a group of anaemic cats than a control group of non-anaemic but systemically unwell cats. No echocardiography performed. Different exclusion criteria for test vs. control groups.
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No published studies.
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Low cTnI.
No published studies for NTproBNP.
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Clinical Use of the Patient-Side NTproBNP SNAP Test: Can It Help to Identify Which Heart Murmurs to Investigate?
A potentially useful test for assessing which heart murmurs to investigate and which to monitor/reassess in time is the patient-side NTproBNP SNAP test. It may also be useful as part of preanaesthetic screening in geriatric cats, where heart disease is common.
This test was validated by comparing a population of cats with moderate to severe cardiomyopathy—”clinically significant”—to a population of cats with either normal echos or mild cardiomyopathy—”not clinically significant” (Machen et al. 2014). The SNAP test works well on EDTA plasma and has a positive cut-off value of approximately 120 pmol/L NTproBNP. If the value is negative, the NTproBNP is probably < 100 pmol/L. Occasionally it may read equivocal if between these values.
The test performed well in validation. To get a feel for how clinically useful the test is in asymptomatic cats with heart murmurs, we should consider the test specifics by Machen et al. and combine these data with the prevalence data from Payne et al. (Table 2).
Table 2. How using the NTproBNP SNAP test may help you to assess likelihood of significant heart disease being present in cats with heart murmurs
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Age group
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Pre-test likelihood of clinically significant heart disease (i.e., prevalence of HCM)
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Post-test likelihood of clinically significant heart disease
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Positive SNAP test
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Negative SNAP test
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6–12
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17.9%
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50.8%
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3%
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1–3
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24.5%
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60.6%
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4.4%
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3–9
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30.1%
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67.1%
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5.7%
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≥ 9
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42.6%
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77.8%
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9.4%
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In summary, a negative test is highly likely to mean that a cat does not have significant heart disease. A positive test is less useful, but it means that echocardiography is indicated (or even just monitoring of respiratory rate, care with intravenous fluids, cautious selection of sedation/anaesthesia protocols, etc.—if echo is prohibited by cost or local access to expertise. In older cats, a positive test is associated with a greater likelihood of clinically significant heart disease being present.
As you can see from Table 2, using the NTproBNP SNAP test allows you to further refine the process of deciding which cats with a heart murmur are likely to require echocardiography. To expand upon an example of a middle-aged female cat, with a grade II/VI systolic heart murmur:
- Around 30% of cats like this have disease. If you recommend echo to every cat like this, around 70% of the time there will be no heart disease that is significant to that cat. However, if you were to use the NTproBNP SNAP test, you could be more selective in which owners to recommend echocardiographic assessment.
- If the SNAP test were positive, this individual cat has a 67% chance of having heart disease. This is clearly not a perfect test for heart disease, but it does mean that there is now more than twice the likelihood of heart disease being present in this cat—probability was 30.1%, now is 67.1%.
- If the test were negative, you could explain to the owner that there is around a 1/20 chance the cat has significant heart disease (5.7%). Echocardiography may be undertaken, but just under 19 out of 20 times the echo will not show clinically relevant cardiomyopathy.
Clearly, the NTproBNP SNAP test should not be used to make decisions regarding treatment and prognosis, because it does not provide a certain diagnosis. However, it may be helpful in assessing need for, or urgency to, perform echocardiography.
References
1. Borgeat K, Connolly DJ, Luis Fuentes V. Cardiac biomarkers in cats. Journal of Veterinary Cardiology. 2015;17:S74–S86.
2. Bijsmans ES, Jepson RE, Wheeler C, et al. Plasma N-terminal probrain natriuretic peptide, vascular endothelial growth factor and cardiac troponin I as novel biomarkers of hypertensive disease and target organ damage in cats. Journal of Veterinary Internal Medicine. 2017;31:650–660.
3. Pierce KV, Rush JE, Freeman LM, et al. Association between survival time and changes in NTproBNP in cats treated for congestive heart failure. Journal of Veterinary Internal Medicine. 2017;31:678–684.