Prospective clinical evaluation of an ELISA B-type natriuretic peptide assay in the diagnosis of congestive heart failure in dogs presenting with cough or dyspnea

BACKGROUND: B-type natriuretic peptide (BNP) is increased in dogs with congestive heart failure (CHF). HYPOTHESIS: The purpose of this study was to evaluate the clinical utility of a novel canine-specific enzyme-linked immunosorbent assay of BNP for the diagnosis of CHF in dogs presenting with either cough or dyspnea. ANIMALS: Three hundred and thirty dogs from 2 large university teaching hospitals. METHODS: We prospectively measured plasma BNP concentrations in 3 groups of dogs: (1) normal adult dogs (n = 75), (2) dogs with asymptomatic heart disease (n = 76), and (3) dogs with cough or dyspnea (n = 179). The final diagnosis of dogs with cough or dyspnea and the severity of CHF (International Small Animal Cardiac Health Council Heart Failure Classification [ISACHC]) were determined by medical record review by a study cardiologist who was blinded to the results of the BNP assay. RESULTS: Dogs with CHF had a higher median BNP concentration (24.6 pg/mL) than dogs with noncardiac causes of cough or dyspnea (2.6 pg/mL) (P < .0001). The area under the curve was 0.91 for the receiver operating curve analysis of the diagnostic accuracy of the BNP measurement to differentiate CHF from other causes of cough or dyspnea. The median BNP concentrations in dogs were 3.0 pg/mL with ISACHC I, 17.8 pg/mL with ISACHC II, and 30.5 pg/mL with ISACHC III. (P < .0001) CONCLUSION AND CLINICAL IMPORTANCE: Measurement of BNP is useful in establishing or in excluding the diagnosis of CHF in dogs with cough or dyspnea. B-type natriuretic peptide concentrations rose significantly as a function of severity of CHF.     

Assessment of plasma cardiac troponin I concentration as a means to differentiate cardiac and noncardiac causes of dyspnea in cats

OBJECTIVE: To determine whether plasma cardiac troponin I (cTnI) concentrations can be used to discriminate cardiac from noncardiac causes of dyspnea in cats. DESIGN: Prospective, multicenter study. ANIMALS: Client-owned cats with dyspnea attributable to congestive heart failure (D-CHF; n=31) or to noncardiac causes (D-NCC; n=12). PROCEDURES: For each cat, plasma cTnI concentration was analyzed by use of a solid-phase radial partition immunoassay; values in cats with D-CHF and D-NCC were compared. A receiver operating characteristic curve was analyzed to determine the accuracy of plasma cTnI concentration for diagnosis of D-CHF. RESULTS: Median plasma concentration of cTnI in cats with D-CHF (1.59 ng/mL; range, 0.20 to 30.24 ng/mL) was significantly higher than in cats with D-NCC (0.165 ng/mL; range, 0.01 to 1.42 ng/mL). With regard to the accuracy of plasma cTnI concentration for diagnosis of D-CHF, the area under the receiver operating characteristic curve was 0.84. At plasma concentrations > or = 0.2 ng/mL, cTnI had 100% sensitivity but only 58% specificity for identification of CHF as the cause of dyspnea. At plasma concentrations > or = 1.43 ng/mL, cTnI had 100% specificity and 58% sensitivity for identification of CHF as the cause of dyspnea. CONCLUSIONS AND CLINICAL RELEVANCE: On the basis of the derived diagnostic limits, CHF as the cause of dyspnea could be ruled in or ruled out without additional diagnostic testing in > 50% of the study cats. Measurement of plasma cTnI concentration may be clinically useful for differentiation of cardiac from noncardiac causes of dyspnea in cats. (J Am Vet     

Prospective screening for occult cardiomyopathy in dogs by measurement of plasma atrial natriuretic peptide, B-type natriuretic peptide, and cardiac troponin-I concentrations

OBJECTIVE: To evaluate the use of measuring plasma concentrations of atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP), and cardiac troponin-I (cTnI) to detect dogs with occult dilated cardiomyopathy (DCM). ANIMALS: 118 client-owned dogs. PROCEDURES: Dogs were prospectively examined by use of ECG; echocardiography; and evaluation of concentrations of ANP, BNP, and cTnI. Occult DCM was diagnosed by evaluation of echocardiographic left ventricular dimensions and detection of ventricular arrhythmias on ECG. Sensitivity and specificity of assays for measurement of plasma concentrations of ANP, BNP, and cTnI to detect dogs with occult DCM were determined. RESULTS: Occult DCM was diagnosed in 21 dogs. A concentration of > 6.21 pg/mL for BNP had a sensitivity of 95.2% and specificity of 61.9% for identifying dogs with occult DCM. In contrast, concentrations of ANP and cTnI had relatively low predictive values. CONCLUSIONS AND CLINICAL RELEVANCE: Blood-based screening for occult DCM in dogs can be accomplished by use of a BNP assay. Additional studies should be performed to optimize this method of screening dogs to detect occult DCM.     

Plasma endothelin-1 immunoreactivity in normal dogs and dogs with acquired heart disease

We sought to measure plasma endothelin-1 (ET-1) concentrations in normal dogs and to compare them with those measured in dogs with acquired heart disease with or without pulmonary edema. A sandwich enzyme-linked immunosorbent assay kit was validated and used to measure ET-1 immunoreactivity in plasma samples obtained from 32 normal dogs and 46 dogs with either dilated cardiomyopathy (DCM, n = 27) or degenerative valvular disease (CDVD, n = 19) with (n = 30) or without (n = 16) overt congestive heart failure (CHF). Plasma ET-1 concentrations (geometric mean, 95% confidence interval of geometric mean) were 1.17 (1.04-1.32) fmol/mL in the 32 normal control dogs, 1.25 (0.981-1.60) fmol/mL in 16 dogs with DCM (n = 9) or CDVD (n = 7) without CHF, and 2.51 (2.10-3.01) fmol/mL in 30 dogs with DCM (n = 18) and CDVD (n = 12) with CHE Plasma immunoreactivity of ET-1 was significantly higher in dogs with CHF in comparison with normal dogs (P < .001) and dogs with heart disease without CHF (P < .001). No significant difference was found between normal dogs and dogs with heart disease but without CHF (P > .05). Significant correlations were between plasma ET-I concentrations and left atrial:aortic ratio (P < .0001, r2 = .39), left ventricular internal dimension at end-diastole indexed to aortic diameter (P < .0001, r2 = .30) or body surface area (BSA) (P = .0071, r2 = .10), and left ventricular internal dimension at end-systole indexed to aortic diameter (P = .0003, r- = .17) or BSA (P = .0008, r2 = .15).     

Comparison of N-terminal pro-atrial natriuretic peptide and three cardiac biomarkers for discriminatory ability of clinical stage in dogs with myxomatous mitral valve disease

Plasma N-terminal pro-atrial natriuretic peptide (NT-proANP) concentration increases with progression of myxomatous mitral valve disease (MMVD) in dogs. This multicentre, prospective study compared plasma NT-proANP, N-terminal pro-brain natriuretic peptide (NT-proBNP), ANP, and cardiac troponin I (cTnI) concentrations in dogs with MMVD for their characteristics and discriminatory ability to detect cardiac dilatation and congestive heart failure (CHF). Thirty-six healthy dogs and 69 dogs with MMVD were included. Clinical variables were obtained via physical examination, thoracic radiography, and echocardiography. The discriminatory ability of each cardiac biomarker (CB) to determine the presence or absence of cardiac dilatation (event 1) and CHF (event 2) was evaluated using the receiver operating characteristic curves. Plasma NT-proANP, NT-proBNP, and ANP concentrations showed a significant association with the left atrium/aorta ratio (P<0.01). The area under the curve of plasma NT-proANP and NT-proBNP concentrations were 0.72 and 0.75, respectively in event1 and 0.72 and 0.76, respectively in event2. Plasma NT-proANP and NT-proBNP concentrations showed sensitivity 80.0 and 80.0%; specificity 67.6 and 64.7% in event1 (cutoff value; 8,497.81 pg/ml and 1,453.00 pmol/l, respectively) and sensitivity 85.7 and 81.0%; specificity 60.4 and 64.6% in event2 (cutoff value; 8,684.33 pg/ml and 1,772.00 pmol/l, respectively). In dogs with MMVD, plasma NT-proANP, NT-proBNP, and ANP concentrations increase with left atrial enlargement. Particularly, plasma NT-proANP and NT-proBNP concentrations appeared to be equally useful in the discriminatory ability to detect cardiac dilatation and CHF.     

Plasma big endothelin-1, atrial natriuretic peptide, aldosterone, and norepinephrine concentrations in normal Doberman Pinschers and Doberman Pinschers with dilated cardiomyopathy

BACKGROUND: Dilated cardiomyopathy (DCM) results in progressive myocardial and circulatory dysfunction causing activation of a number of neurohormonal systems, including the endothelin (ET) system, which is only beginning to be described in clinical veterinary medicine. Measurement of these circulating neurohormones possesses potential utility in the diagnosis, staging, and assessment of prognosis in cardiac disease. HYPOTHESIS: We hypothesized that plasma big ET-1, norepinephrine (NE), aldosterone, and atrial natriuretic peptide (ANP) concentrations in normal Dobermans would differ from those in Dobermans with DCM, and that concentrations of these hormones would be associated with time to congestive heart failure (CHF) or death. ANIMALS: Thirty client-owned Dobermans (10 each of normal, occult DCM, and overt DCM) were included in the study. METHODS: Dogs underwent an echocardiogram, ECG, and blood sample collection. Neurohormones were measured by high-pressure liquid chromatography (NE) or commercial assays. RESULTS: Dogs with occult DCM had significantly higher ANP concentrations compared with normal dogs (least squares means [95% confidence interval, CI]: occult female 53.7 pg/mL [40.2-71.7] versus normal female 31.6 pg/mL [24.8-40.3], P = .026; occult male 86.1 pg/mL [64.7-115] versus normal male 12.1 pg/mL [5.1-28.7], P = .011). Dogs with overt DCM had significantly higher concentrations of all neurohormones compared with the normal group. Furthermore, increasing big ET-1 (risk ratio [RR] 2.7, CI 1.3-8.6, P = .01) and NE concentrations (RR 3.9, CI 1.1-18.1, P = .03) over 1 month were associated with a shorter survival time. CONCLUSIONS AND CLINICAL IMPORTANCE: High ANP concentrations can identify dogs with advanced occult DCM. Increasing big ET-1 or NE concentrations over time can be useful predictors of poor prognosis.     

Circulating natriuretic peptides in cats with heart disease

BACKGROUND: Circulating natriuretic peptide concentrations are increased in cats with myocardial dysfunction. HYPOTHESIS: Serum N-terminal fragment of proatrial natriuretic peptide (NT-proANP) and NT-probrain natriuretic peptide (proBNP) concentrations may predict the presence of heart disease (HD) and congestive heart failure (CHF). A positive relationship is also predicted among natriuretic peptide (NP) concentrations, a noninvasive estimate of left ventricular filling pressure (E/E(a)), and an echocardiographic measure of left atrial (LA) size (LA/aortic diameter [Ao]). METHODS: Serum NP concentrations were measured in 28 healthy control and 50 study cats using sandwich enzyme immunoassays. The study group comprised cats, with HD but no CHF (HD - CHF, n = 17) and cats with CHF (HD + CHF, n = 33). The relationship among NP concentrations, LA size, and E/E(a) was examined. The ability of NP to distinguish control from study cats, and HD - CHF from HD + CHF cats, was explored using receiver operator curve analysis. RESULTS: NP concentrations were significantly lower in control than in study cats (P= .0001). The NT-proBNP concentrations were positively correlated with LA/Ao ratio (rho= 0.34; P= .02) and with E/E(a) ratio (rho= 0.68; P < .05). An NT-proBNP concentration of 49 fmol/mL gave a sensitivity and specificity of 100 and 89.3%, respectively, for correctly distinguishing 96.2% of control from study cats. Pairwise comparisons of the areas under the curve identified a statistically significant difference (P= .011) between NT-proANP and NT-proBNP to distinguish control from study cats. NT-proANP and NT-proBNP concentrations were significantly higher in HD + CHF cats than in HD - CHF cats (P= .0023 and .0001, respectively). CONCLUSIONS: Serum concentrations of NT-proANP and particularly NT-proBNP were different in healthy control cats, asymptomatic cats with HD, and cats with CHF, suggesting that measurement of NP concentrations may prove clinically useful as an initial screening test for cats with suspected cardiac disease.     

NT-proBNP, NT-proANP and cTnI concentrations in dogs with pre-capillary pulmonary hypertension

Objectives

To compare [NT-proBNP], [NT-proANP] and [cTnI] between control dogs with respiratory disease without pulmonary hypertension (PH) and dogs with pre-capillary PH, and to assess the accuracy of [NT-proBNP], [NT-proANP], [cTnI] to predict Doppler-derived peak tricuspid regurgitation (TR) gradient.

Animals

20 dogs. 8 control dogs with respiratory disease with no PH and 12 with pre-capillary PH.

Methods

[NT-proBNP], [NT-proANP] and [cTnI] were compared between the 2 groups and simple linear regression analysis was used to predict peak TR gradients from various blood biomarkers.

Results

Median [NT-proBNP] was higher in the dogs with PH (2011 pmol/L, 274–7713 pmol/L) compared to control dogs (744 pmol/L; 531–2710 pmol/L) (p = 0.0339). [NT-proBNP] was associated with peak TR gradient (R² = 0.7851, p = 0.0001). Median [NT-proANP] did not differ between dogs with PH (1747 fmol/L; 894–2884 fmol/L) and control dogs (1209 fmol/L; 976–1389 fmol/L (p = 0.058). [NT-proANP] was not associated with peak TR gradient (R² = 0.2780, p = 0.0781). Median [cTnI] did not differ between dogs with PH (0.2850 ng/mL; 0.19–1.13 ng/mL) and control dogs (0.2 ng/mL; 0.19–0.82 ng/mL, p = 0.3051). Median [TnI] was not associated with peak TR gradient (R² = 0.024, p = 0.6307).

Conclusions

[NT-proBNP] concentration is significantly higher in dogs with pre-capillary PH when compared to dogs with respiratory disease without PH, and [NT-proBNP] may be useful to predict the severity of estimated PH. Elevations in [NT-proBNP] due to pre-capillary PH may complicate the interpretation of [NT-proBNP] elevations in patients presenting with cardiorespiratory abnormalities. [NT-proANP] and [cTnI] were not elevated in dogs with pre-capillary PH.     

Brain natriuretic peptide concentration in dogs with heart disease and congestive heart failure

Plasma brain natriuretic peptide concentration ([BNP]) is high in humans with cardiac disease and is further increased with congestive heart failure (CHF). The hypotheses of this study were that dogs with moderate to severe mitral regurgitation due to myxomatous mitral valve disease (MVD) would have increased plasma [BNP] compared to normal dogs, that plasma [BNP] would be higher in dogs with CHP, and that plasma [BNP] would predict premature death from cardiovascular disease. The study population consisted of 34 dogs: 9 normal dogs and 25 dogs with MVD. Patients were divided into 4 groups: group 1-10 dogs with moderate to severe MVD and no radiographic evidence of CHF; group II--6 dogs with severe MVD and mild CHF; group III--7 dogs with severe MVD and moderate CHF; and group IV--2 dogs with severe MVD and severe CHF. Diagnostic tests included thoracic radiographs, an echocardiogram, a serum chemistry profile, and the measurement of plasma [BNP] by a canine-specific radioimmunoassay. There was a significant positive correlation between the plasma [BNP] and heart disease/failure groups (P = .0036). Plasma [BNP] increased with progressively increasing severity of MVD and CHE Group I dogs had higher plasma [BNP] than did control dogs (P < .0001), and plasma [BNP] was higher in dogs with CHF (groups II-IV versus group I; P = .012). Plasma [BNP] was also weakly positively correlated with left atrial size (r = 0.43, P = .04). For every 10-pg/mL increase in plasma [BNP], the mortality rate over 4 months' time increased approximately 44%.     

Cardiac troponin-I concentration in dogs with cardiac disease

Cardiac troponin-I (cTnI) is a highly sensitive and specific marker of myocardial injury and can be detected in plasma by immunoassay techniques. The purpose of this study was to establish a reference range for plasma cTnI in a population of healthy dogs using a human immunoassay system and to determine whether plasma cTnI concentrations were high in dogs with acquired or congenital heart disease, specifically cardiomyopathy (CM), degenerative mitral valve disease (MVD), and subvalvular aortic stenosis (SAS). In total, 269 dogs were examined by physical examination, electrocardiography, echocardiography, and plasma cTnI assay. In 176 healthy dogs, median cTnI was 0.03 ng/mL (upper 95th percentile = 0.11 ng/mL). Compared with the healthy population, median plasma cTnI was increased in dogs with CM (0.14 ng/mL; range, 0.03-1.88 ng/mL; P < .001; n = 26), in dogs with MVD (0.11 ng/mL; range, 0.01-9.53 ng/mL; P < .001; n = 37), and in dogs with SAS (0.08 ng/mL; range, 0.01-0.94 ng/mL; P < .001; n = 30). In dogs with CM and MVD, plasma cTnI was correlated with left ventricular and left atrial size. In dogs with SAS, cTnI demonstrated a modest correlation with ventricular wall thickness. In dogs with CM, the median survival time of those with cTnI >0.20 ng/mL was significantly shorter than median survival time of those with cTnI <0.20 ng/mL (112 days versus 357 days; P = .006). Plasma cTnI is high in dogs with cardiac disease, correlates with heart size and survival, and can be used as a blood-based biomarker of cardiac disease.     

Measurements of plasma endothelin immunoreactivity in healthy cats and cats with cardiomyopathy

Plasma concentrations of endothelin-1 (ET-1), the most potent endogenous pressor substance discovered to date, are abnormally high in humans with congestive heart failure (CHF), and they correlate with the degree of functional impairment. We sought first to validate a human sandwich ELISA kit that targets that portion of the amino acid sequence that is identical in cats. The assay demonstrated linearity (R2 = .9968) and parallelism (P = .5339), recovery of spiked human ET-1 in cat plasma averaged 98.7%, and intraassay precision had a coefficient of variation <10%. We subsequently determined ET-1 immunoreactivity in healthy cats and in cats with myocardial disease with and without CHF, systemic thromboembolism (STE), or both. Plasma ET-1 immunoreactivity was measured in 12 healthy cats and in 28 cats with primary myocardial disease, including hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), or restrictive or unclassified cardiomyopathy (RCM and UCM), respectively. Plasma ET mean (95% CI) concentrations were 0.777 (0.6536-0.924) fmol/mL in the control cats, 1.427 (0.922-2.209) fmol/mL in 12 cats with cardiomyopathy (HCM = 11, RCM/UCM = 1) but without CHF or evidence of STE, and 2.360 (1.666-3.343) fmol/mL in 16 cats with cardiomyopathy (HCM = 8, RCM/UCM = 7, DCM = 1) and CHF (n = 15) or STE (n = 4). Plasma immunoreactivity of ET-1 was significantly higher in cats with myocardial disease without CHF/STE versus normal cats (P < .05) and in cats with myocardial disease with CHF/STE versus normal cats (P < .001).     

Assessment of the diagnostic accuracy of circulating natriuretic peptide concentrations to distinguish between cats with cardiac and non-cardiac causes of respiratory distress

ObjectivesTo determine if serum natriuretic peptide (NP) concentrations could distinguish cardiac from non-cardiac causes of respiratory distress (RD) in cats.AnimalsSeventy-four cats from 1 university hospital were used.MethodsSerum NP concentrations were measured in 41 cats with non-cardiac respiratory distress (RD-NC) and compared to 33 cats with RD due to congestive heart failure (RD + CHF) using sandwich enzyme immunoassays (ELISA).ResultsRD-NC cats had lower (P = 0.0001) median NT-proANP and NT-proBNP concentrations (614 and 45 fmol/mL, respectively) than RD + CHF cats (1690 and 523 fmol/mL, respectively). The area under the curve was 0.88 and 0.96 for the receiver operating curve analysis of the diagnostic accuracy of NT-proANP and NT-proBNP concentrations to discriminate RD + CHF from RD-NC cats (P = 0.036). An optimum cut-off concentration of 986 fmol/mL for NT-proANP and 220 fmol/mL for NT-proBNP accurately discriminated RD-NC from RC + CHF cats with a sensitivity of 93.8% and 93.9% and a specificity of 80.3% and 87.8%, respectively.ConclusionsSerum NP concentrations were different in RD + CHF cats compared to RD-NC cats. Evaluation of circulating NP concentrations may be helpful in the initial approach to cats presenting with respiratory distress, particularly if advances in ELISA technology result in a rapid cage-side test.     

Assessment of plasma brain natriuretic peptide concentration in Boxers with arrhythmogenic right ventricular cardiomyopathy

OBJECTIVE: To determine whether Boxers with a clinical diagnosis of arrhythmogenic right ventricular cardiomyopathy (ARVC) have increased plasma concentrations of brain natriuretic peptide (BNP), compared with concentrations in clinically normal dogs. ANIMALS: 13 Boxers with ARVC, 9 clinically normal Boxers, 10 clinically normal non-Boxer dogs, and 5 hound dogs with systolic dysfunction. PROCEDURE: All Boxers were evaluated via 24-hour ambulatory electrocardiography and echocardiography; the number of ventricular premature contractions (VPCs) per 24 hours was assessed. Hound dogs with cardiac pacing-induced systolic dysfunction (positive control dogs) and clinically normal non-Boxer dogs (negative control dogs) were evaluated echocardiographically. Three milliliters of blood was collected from each dog for measurement of plasma BNP concentration by use of a radioimmunoassay. RESULTS: Mean +/- SD plasma BNP concentration for the ARVC-affected Boxers, clinically normal Boxers, negative control dogs, and positive control dogs was 11.0 +/- 4.6 pg/mL, 7.9 +/- 3.2 pg/mL, 11.5 +/- 4.9 pg/mL, and 100.8 +/- 56.8 pg/mL, respectively. Compared with findings in the positive control group, plasma BNP concentration in each of the other 3 groups was significantly different. There was no significant difference in BNP concentration between the 2 groups of Boxers. A significant correlation between plasma BNP concentration and number of VPCs per 24 hours in the ARVC-affected Boxers was not identified. CONCLUSIONS AND CLINICAL RELEVANCE: A significant difference in BNP concentration between Boxers with ARVC and clinically normal Boxers was not identified. Results suggest that BNP concentration may not be an indicator of ARVC in Boxers.     

Antioxidant status and biomarkers of oxidative stress in dogs with congestive heart failure

Alterations in antioxidant status and oxidative stress have been documented in dogs with dilated cardiomyopathy (DCM). The purpose of this study was to more broadly assess this relationship in dogs with congestive heart failure (CHF). Malondialdehyde (MDA), 8-F(2alpha)-isoprostane, protein carbonyls, reduced (GSH) and oxidized (GSSG) glutathione, vitamins A, C, and E, and oxygen radical absorbance capacity (ORAC) were measured from a single venous blood sample from dogs with CHF secondary to DCM or chronic valvular disease (CVD) and in healthy controls. Nineteen dogs with CHF (14 CVD and 5 DCM) and 12 healthy controls were enrolled in the study. Concentrations of 8-F(2alpha)-isoprostane (CHF: 44.6 pg/mL [range, 27.1-98.0 pg/mL], controls: 25.3 pg/ mL [range, 11.1-80.4 pg/mL]) but not MDA (CHF: 4.11 microM [range, 1.89-6.39 microM], controls: 3.88 microM [range, 2.14-4.72 microM]) or protein carbonyls (0.69 nmol/mg protein [range, 0.37-1.67 nmol/mg protein], controls: 0.80 nmol/mg protein [range, 0.40-1.14 nmol/mg protein]) were significantly higher in the dogs with CHF than in the controls. Vitamin E concentration (CHF: 2,215 microg/ dL [range, 916-3,499 microg/dL], controls: 2,820 microg/dL [range, 1,738-3,775 microg/dL]) and GSH:GSSG (CHF: 12.0 [range, 3.69-30.1], controls: 22.7 [range, 12.5-227]) were significantly lower, whereas ORAC (CHF: 824 micromol Trolox equivalent/L [range, 304-984], controls: 497 micromol Trolox equivalent/L [range, 258-759]) and vitamin C (CHF: 0.90 mg/dL [range, 0.55-2.02 mg/dL], controls: 0.72 mg/dL [range, 0.43-0.85 mg/dL]) concentrations were higher in dogs with CHF than in controls. Vitamin A concentrations were not different between dogs with CHF and controls. No differences in any of the parameters were detected between dogs with DCM versus those with CVD. Some antioxidant defenses are decreased in dogs with CHF, and some biomarkers of oxidative stress are increased in dogs with CHF. The effect of dietary interventions to correct this imbalance in antioxidant defenses warrants further study.     

Comparison of canine cardiac troponin I concentrations as determined by 3 analyzers

BACKGROUND: Recent interest in cardiac biomarkers has led to the validation of several commercial analyzers for cardiac troponin I (cTnI) evaluation in dogs; however, these analyzers have not been standardized. HYPOTHESIS: It was hypothesized that canine plasma cTnI concentrations as determined by 3 different analyzers would be similar. ANIMALS: Twenty-three dogs with cardiac disease were studied. METHODS: Reconstituted purified canine free cTnI was diluted with canine plasma to 8 concentrations (0.01, 0.1, 0.78, 1.56, 3.13, 6.25, 12.5, and 25 ng/mL), for analysis by 3 analyzers, the Biosite Triage Meter, the Dade-Behring Stratus, and the Beckman-Coulter Access AccuTnI. Plasma samples from 23 dogs with cardiac disease were also analyzed for cTnI concentrations on all analyzers. RESULTS: Troponin I concentrations in sick dogs were <0.05-5.72 ng/mL (Biosite), 0.02-11.1 ng/mL (Access), and 0.02-9.73 ng/mL (Stratus). Analyzer results were highly correlated with each other (r = 0.97 to 1.0 for purified dilutions, r = 0.61 to 0.89 for samples from dogs); however, the limits of agreement were wide for both purified dilutions and clinical samples. Recovery was highest for the Access (334-1467%) and lowest for the Biosite (38-60%); Stratus 52-233%. Analyzer variability was lowest for the Access (1.2-10.4%) and highest for the Stratus (4.8-33.6%); Biosite 2.8-16.5%. CONCLUSIONS AND CLINICAL IMPORTANCE: Results from this study suggest that although canine cTnI values obtained from the Biosite, Stratus, and Access analyzers are closely correlated, they cannot be directly compared with each other. In the absence of a gold standard none of the analyzers can be considered more correct than the others.     

Assessment of a point‐of‐care cardiac troponin I test to differentiate cardiac from noncardiac causes of respiratory distress in dogs

Objectives – To (1) determine a reference interval for cardiac troponin I (cTnI) using a point‐of‐care device in normal dogs and compare the results with those published by the manufacturer and (2) determine if cTnI differs among dogs with cardiogenic and noncardiogenic respiratory distress. Design – Prospective observational study. Setting – Emergency and referral veterinary hospital. Animals – Twenty‐six clinically normal dogs and 67 dogs in respiratory distress. Interventions – All dogs underwent whole blood sampling for cTnI concentrations. Measurements and Results – Normal dogs had a median cTnI concentration of 0.03 ng/mL (range 0–0.11 ng/mL). Thirty‐six dogs were diagnosed with noncardiogenic respiratory distress with a median cTnI concentration of 0.14 ng/mL (range 0.01–4.31 ng/mL). Thirty‐one dogs were diagnosed with cardiogenic respiratory distress with a median cTnI concentration of 1.74 ng/mL (range 0.05–17.1 ng/mL). A significant difference between cTnI concentrations in normal dogs and dogs with noncardiogenic respiratory distress was not detected. Significant differences in cTnI concentrations were found between normals versus cardiogenic and cardiogenic versus noncardiogenic respiratory distress groups. Significant differences in cTnI concentrations were identified in >10 when compared with the <5 and the 5–10 years of age groups. Receiver operating curve analysis identified cTnI concentrations >1.5 ng/mL as the optimal “cut‐off point” having a sensitivity of 78% and specificity of 51.5%. The area under the receiver operating curve was 0.72. Overall test accuracy was 65%. Conclusions – cTnI concentrations were significantly increased in dogs with cardiogenic respiratory distress versus dogs with noncardiogenic respiratory distress and normal dogs. A significant difference between normal dogs and dogs with noncardiogenic causes of respiratory distress was detected. Although highly sensitive when cTnI concentrations exceed 1.5 ng/mL, the test has low specificity. Assessment of cTnI by the methodology used cannot be recommended as the sole diagnostic modality for evaluating the cause of respiratory distress in dogs.     

Diagnostic potential of natriuretic peptides in the occult phase of golden retriever muscular dystrophy cardiomyopathy

The objective of the study was to determine whether the plasma concentrations of atrial and brain natriuretic peptides (ANP and BNP, respectively) could be reliable markers of cardiac alterations during occult cardiomyopathy in Golden Retriever Muscular Dystrophy (GRMD). Fifty Golden Retrievers without any clinical or radiographic sign of heart disease were included in this study (21 GRMD dogs and 29 controls). Controls and GRMD dogs were divided into 2 subgroups according to age (< and > or =12 months old, respectively). All dogs underwent echocardiography and determination of BNP and ANP plasma concentrations by radioimmunoassay. No ventricular dilatation or dysfunction was observed in either control or GRMD dogs. ANP plasma concentration did not differ significantly between controls and GRMD dogs (mean +/- SD = 72 +/- 49 versus 58 +/- 23 pg/mL, respectively, P = .21). This finding was confirmed in both subgroups of dogs (ie, those < and > or =12 months old). In contrast, BNP plasma concentrations were significantly higher in GRMD dogs than in controls (mean +/- SD = 117 +/- 92 versus 46 +/- 22 pg/mL, respectively, P < .05). In dogs > or =12 months old, sensitivity and specificity of BNP for identifying GRMD with a cutoff of 65 pg/mL were 78 and 86%, respectively. For the same cutoff value, sensitivity dropped to 42%, whereas specificity reached 100% in dogs <12 months old. In conclusion, BNP may be a useful biochemical marker of asymptomatic cardiomyopathy. However, this peptide does not allow very early detection because its optimal discriminatory power was observed in adult dogs (ie, > or =12 months of age).     

Measurement of plasma atrial natriuretic peptide as an indicator of prognosis in dogs with cardiac disease

Twenty-three dogs with heart failure were evaluated in a 12-month study by measuring baseline plasma atrial natriuretic peptide (ANP) concentrations. Ten dogs were classified as having mild to moderate cardiac disease (group 1) and 13 dogs were classified as having severe cardiac disease (group 2). The mean plasma ANP concentration for the group 1 dogs was 64 +/- 45 pg/mL and for the group 2 dogs, 328 +/- 122 pg/mL. The median survival time (1,095 d) for group 1 dogs was significantly greater (P < 0.05) than for group 2 dogs (58 d). A significantly (P < 0.05) greater median survival was noted for dogs with plasma ANP < 95 pg/mL (1095 d) compared with those with ANP > 95 pg/mL (58 d). Plasma ANP concentrations are a potential noninvasive predictor of survival in dogs with heart failure.     

Cardiac troponin I in the normal dog and cat

Cardiac troponin I (cTnI) has proven to be a highly specific and sensitive marker for myocardial cellular damage in many mammalian species. The structure of cTnI is highly conserved across species, and assays for human cTnI (including the one used in the current study) have been validated in the dog. Blood concentrations of cTnI rise rapidly after cardiomyocyte damage, and assay of cTnI potentially may be valuable in many clinical diseases. The purpose of this study was to establish the normal range of cTnI in heparinized plasma of dogs and cats. Forty one clinically normal dogs and 21 cats were included in the study. One to 3 milliliters of blood were collected by venipuncture into lithium heparin vacutainers for analysis of cTnI (Stratusz CS). The range of plasma cTnI concentrations in dogs was <0.03 to 0.07 ng/mL with a mean of 0.02 ng/mL, with the upper tolerance limit (0.07 ng/mL) at the 90th percentile with 95% confidence. In cats, the range was <0.03 to 0.16 ng/mL with a mean of 0.04 ng/mL, and the upper tolerance limit (0.16 ng/mL) at the 90th percentile as well with 90% confidence. This study establishes preliminary normal ranges of plasma cTnI in normal dogs and cats for comparison to dogs and cats with myocardial injury or disease.     

Increased NT-proANP predicts risk of congestive heart failure in Cavalier King Charles spaniels with mitral regurgitation caused by myxomatous valve disease

ObjectivesTo evaluate the predictive value of plasma N-terminal pro-atrial natriuretic peptide (NT-proANP) and nitric oxide end-products (NOx) as markers for progression of mitral regurgitation caused by myxomatous mitral valve disease.AnimalsSeventy-eight privately owned Cavalier King Charles spaniels with naturally occurring myxomatous mitral valve disease.MethodsProspective longitudinal study comprising 312 measurements over a 4.5 year period. Clinical values were recorded, NT-proANP concentrations were measured by radioimmunoassay, and NOx were analyzed colorimetrically. To predict congestive heart failure (CHF), Cox proportional hazards models with time-varying covariates were constructed.ResultsThe hazard ratio for NT-proANP (per 1000 pmol/l increase) to predict future CHF was 6.7 (95% confidence interval, 3.6–12.5; p < 0.001). The median time to CHF for dogs with NT-proANP levels >1000 pmol/l was 11 months (95% confidence interval, 5.6–12.6 months), compared to 54 months (46 – infinity) for dogs with concentrations ≤1000 pmol/l (p < 0.001). Due to intra- and inter-individual variability, most corresponding analyses for NOx were insignificant but dogs reaching CHF had a lower mean NOx concentration than dogs not reaching CHF (23 vs. 28 μmol/l, p = 0.016). Risk of CHF increased with increase in heart rate (>130 beats per minute) and grade of murmur (≥3/6).ConclusionsThe risk of CHF due to mitral regurgitation is increased in dogs with blood NT-proANP concentrations above 1000 pmol/l. Measurement of NT-proANP can be a valuable tool to identify dogs that may develop CHF within months.