Predictive value of natriuretic peptides in dogs with mitral valve disease

Tarnow, Inge; Olsen, Lisbeth H.; Kvart, Clarence; Höglund, Katja; Moesgaard, S.G.; Kamstrup, Thea S.; Pedersen, Henrik D.; Häggström, Jens

doi:10.1016/j.tvjl.2007.12.026

Cited by 65 publications

(80 citation statements)

References 21 publications

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“…Increased plasma NP concentrations have been identified in dogs with dilated cardiomyopathy (DCM) 2, 3, 4, 5, 6, 7. Furthermore, NP concentrations have been shown to increase with increasing disease severity in dogs with myxomatous mitral valve disease (MMVD),3, 8, 9, 10, 11 and NT‐proBNP has been suggested to be predictive of outcome in dogs with MMVD 9, 12, 13, 14, 15, 16. Natriuretic peptides also have been found useful to distinguish CHF from respiratory disease 12, 17, 18, 19, 20.…”

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“…Natriuretic peptides also have been found useful to distinguish CHF from respiratory disease 12, 17, 18, 19, 20. However, in several studies of dogs, considerable overlap between investigated groups has been identified 2, 3, 8, 9, 11, 17, 18, 19…”

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confidence: 99%

“…There are, however, numerous physiologic and pathologic factors in addition to cardiac function that may influence NP concentrations in humans as well as dogs, and concerns exist about how to adjust reference limits and cutoff‐values with regard to these factors 3, 6, 8, 9, 17, 18, 19, 30, 31, 32…”

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Breed Differences in Natriuretic Peptides in Healthy Dogs

Sjöstrand

Wess

Ljungvall

et al. 2014

Veterinary Internal Medicne

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BackgroundMeasurement of plasma concentration of natriuretic peptides (NPs) is suggested to be of value in diagnosis of cardiac disease in dogs, but many factors other than cardiac status may influence their concentrations. Dog breed potentially is 1 such factor.ObjectiveTo investigate breed variation in plasma concentrations of pro‐atrial natriuretic peptide 31‐67 (proANP 31‐67) and N‐terminal B‐type natriuretic peptide (NT‐proBNP) in healthy dogs.Animals535 healthy, privately owned dogs of 9 breeds were examined at 5 centers as part of the European Union (EU) LUPA project.MethodsAbsence of cardiovascular disease or other clinically relevant organ‐related or systemic disease was ensured by thorough clinical investigation. Plasma concentrations of proANP 31‐67 and NT‐proBNP were measured by commercially available ELISA assays.ResultsOverall significant breed differences were found in proANP 31‐67 (P < .0001) and NT‐proBNP (P < .0001) concentrations. Pair‐wise comparisons between breeds differed in approximately 50% of comparisons for proANP 31‐67 as well as NT‐proBNP concentrations, both when including all centers and within each center. Interquartile range was large for many breeds, especially for NT‐proBNP. Among included breeds, Labrador Retrievers and Newfoundlands had highest median NT‐proBNP concentrations with concentrations 3 times as high as those of Dachshunds. German Shepherds and Cavalier King Charles Spaniels had the highest median proANP 31‐67 concentrations, twice the median concentration in Doberman Pinschers.Conclusions and Clinical ImportanceConsiderable interbreed variation in plasma NP concentrations was found in healthy dogs. Intrabreed variation was large in several breeds, especially for NT‐proBNP. Additional studies are needed to establish breed‐specific reference ranges.

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Breed Differences in Natriuretic Peptides in Healthy Dogs

Sjöstrand

Wess

Ljungvall

et al. 2014

Veterinary Internal Medicne

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“…Measurement of natriuretic peptides including canine N‐terminal pro‐brain natriuretic peptide concentration ([NT‐proBNP]) provides insights to distinguish cardiac from noncardiac respiratory distress,3, 4, 5, 6, 7, 8 assess heart disease (HD) severity,7, 9, 10, 11 predict onset of CHF,11 provide prognostic information in myxomatous mitral valve disease (MMVD),10, 11, 12, 13, 14 and dilated cardiomyopathy (DCM),15, 16 and help with treatment decisions 17…”

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Relationship of Plasma N‐terminal Pro‐brain Natriuretic Peptide Concentrations to Heart Failure Classification and Cause of Respiratory Distress in Dogs Using a 2nd Generation ELISA Assay

Fox

Oyama

Hezzell

et al. 2014

Veterinary Internal Medicne

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BackgroundCardiac biomarkers provide objective data that augments clinical assessment of heart disease (HD).Hypothesis/ObjectivesDetermine the utility of plasma N‐terminal pro‐brain natriuretic peptide concentration [NT‐proBNP] measured by a 2nd generation canine ELISA assay to discriminate cardiac from noncardiac respiratory distress and evaluate HD severity.AnimalsClient‐owned dogs (n = 291).MethodsMulticenter, cross‐sectional, prospective investigation. Medical history, physical examination, echocardiography, and thoracic radiography classified 113 asymptomatic dogs (group 1, n = 39 without HD; group 2, n = 74 with HD), and 178 with respiratory distress (group 3, n = 104 respiratory disease, either with or without concurrent HD; group 4, n = 74 with congestive heart failure [CHF]). HD severity was graded using International Small Animal Cardiac Health Council (ISACHC) and ACVIM Consensus (ACVIM‐HD) schemes without knowledge of [NT‐proBNP] results. Receiver‐operating characteristic curve analysis assessed the capacity of [NT‐proBNP] to discriminate between dogs with cardiac and noncardiac respiratory distress. Multivariate general linear models containing key clinical variables tested associations between [NT‐proBNP] and HD severity.ResultsPlasma [NT‐proBNP] (median; IQR) was higher in CHF dogs (5,110; 2,769–8,466 pmol/L) compared to those with noncardiac respiratory distress (1,287; 672–2,704 pmol/L; P < .0001). A cut‐off >2,447 pmol/L discriminated CHF from noncardiac respiratory distress (81.1% sensitivity; 73.1% specificity; area under curve, 0.84). A multivariate model comprising left atrial to aortic ratio, heart rate, left ventricular diameter, end‐systole, and ACVIM‐HD scheme most accurately associated average plasma [NT‐proBNP] with HD severity.Conclusions and Clinical ImportancePlasma [NT‐proBNP] was useful for discriminating CHF from noncardiac respiratory distress. Average plasma [NT‐BNP] increased significantly as a function of HD severity using the ACVIM‐HD classification scheme.

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“…Genotyping of the selected SNPs and quantification of systemic levels of MMP-2 and MMP-9 were assessed for evaluating associations between the genotypes and MVD risk and with the clinical disease phenotypes (i.e., circulating amount of two enzymes, severity, and complications). For this last objective, systemic levels of pro-atrial natriuretic peptide (pro-ANP) were also quantified due to the emerging evidence suggesting a significant association between high circulating pro-ANP levels and severity and complication of degenerative MVDs [19][20][21][22]. These investigations might permit to evidence whether the genetic variants selected and the circulating blood levels of their molecules and the pro-ANP may be potential predictive, diagnostic, and prognostic biomarkers.…”

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Associations of rs3918242 and rs2285053 MMP-9 and MMP-2 polymorphisms with the risk, severity, and short- and long-term complications of degenerative mitral valve diseases: a 4.8-year prospective cohort study

Balistreri

Allegra

Crapanzano

et al. 2016

Cardiovascular Pathology

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Keywords:Degenerative forms of mitral valve diseases Metalloproteinases rs3918242, rs243865, rs2285053 MMP-2 and MMP-9 gene SNPs Management and outcome Background: Degenerative forms of mitral valve diseases (MVDs) are very complex pathologies. Thus, it is difficult to make generalizations about the disease pathways or genetic risk factors contributing to these diseases. However, a key role of metalloproteinases (MMPs) in their pathophysiology is emerging. Thus, we performed for the first time a perspective study to assess eventual associations of some functional single nucleotide polymorphisms (SNPs) in MMP-2 and MMP-9 genes with the MVD risk, symptom severity, and short-and long-term (4.8 years) complications. Materials and methods: For this purpose, 90 patients and two control groups were genotyped for rs3918242, rs243865, and rs2285053 MMP-2 and MMP-9 gene SNPs, and systemic levels of pro-atrial natriuretic peptide (pro-ANP) and two enzymes were quantified and correlated to genotypes of MMP-2 and MMP-9 SNPs studied. In addition, associations between these SNPs and symptom severity and short-and long-term (4.8 years) complications were evaluated. Results: Interestingly, rs3918242 MMP-9 and rs2285053 MMP-2 SNPs were significantly represented in cases than two control groups and were associated with a higher MVD risk, as demonstrated using dominant/recessive models. Cases stratified for NYHA symptoms and particularly those NYHA III+IV with rs3918242 CT+TT MMP-9 and rs2285053CT+TT genotypes also showed higher severity related to significant higher systemic levels of MMP enzymes and pro-ANP at enrolment and 4.8 follow-up times. In addition, cases with these genotypes and particularly those NYHA III+IV had a very significant percentage of complications, particularly at the 4.8 follow-up. Surprisingly, 20% of patient controls developed MVD at 4.8-year follow-up and were carriers of these genotypes. Conclusion: Thus, the associations observed seem to suggest that the two SNPs might represent useful biomarkers and targets for preventing and monitoring MVDs and developing personalized treatments, consenting a more appropriate management and outcome.

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Predictive value of natriuretic peptides in dogs with mitral valve disease

Cited by 65 publications

References 21 publications

Breed Differences in Natriuretic Peptides in Healthy Dogs

Breed Differences in Natriuretic Peptides in Healthy Dogs

Relationship of Plasma N‐terminal Pro‐brain Natriuretic Peptide Concentrations to Heart Failure Classification and Cause of Respiratory Distress in Dogs Using a 2nd Generation ELISA Assay

Associations of rs3918242 and rs2285053 MMP-9 and MMP-2 polymorphisms with the risk, severity, and short- and long-term complications of degenerative mitral valve diseases: a 4.8-year prospective cohort study

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