Analytical validation, sample stability, and clinical evaluation of a new high-sensitivity cardiac troponin I immunoassay for use in dogs, with comparison to a previous ultrasensitive assay.

Cardiac troponin I (cTnI) is considered the gold standard biomarker for myocardial injury and shows a high degree of homology between humans and dogs. The ADVIA Centaur XP High-Sensitivity Troponin I (AC-cTnI-HS) assay has been validated for use in humans but not dogs. The study objectives were to analytically validate the AC-cTnI-HS assay in dogs, to assess correlation between the AC-cTnI-HS and a previous ADVIA Centaur TnI-Ultra (AC-cTnI-U) assay, to assess cTnI sample storage stability, and to clinically evaluate the AC-cTnI-HS assay in healthy dogs and dogs with cardiac disease. Canine serum samples were used for analytical validation. Intra- and inter-assay variability, dilutional parallelism, and spiking recovery were assessed. Samples from 196 client-owned dogs were evaluated (healthy dogs (n = 39) or dogs with congenital heart disease (n = 54), myxomatous mitral valve disease (n = 68), dilated cardiomyopathy (n = 15), or myocarditis (n = 20)). Inter- and intra-assay coefficient of variation (%CV) was between 2.8-41.4% and 3.8-30.2%, respectively, with pools with concentrations >20 pg/mL all having %CVs <10%. The observed to expected ratios for dilutional parallelism and spiking recovery experiments ranged between 92.3 and 266.7.0% and 84.3 and 108%, respectively. A strong correlation between the AC-cTnI-HS and AC-cTnI-U assays was observed (Spearman's ρ = 0.927), though a proportional bias existed, with AC-cTnI-HS assay concentrations being proportionally lower than AC-cTnI-U assay concentrations. Serum samples stored at -80°C had stable cTnI measurements for up to 2.7 years and after a single freeze-thaw cycle. Healthy dogs and dogs with congenital heart disease had significantly lower cTnI concentrations than dogs in the other three groups. The AC-cTnI-HS assay precisely, reproducibly, and accurately measures cTnI concentrations in dog serum with cTnI concentrations >20 pg/mL.

Whole blood and plasma taurine reference intervals in adult Cavalier King Charles Spaniels and correlations between taurine concentration, diet and mitral valve disease.

OBJECTIVE: To determine breed-specific reference intervals for whole blood (WB) and plasma taurine concentrations in adult, overtly healthy Cavalier King Charles Spaniels (CKCSs) and determine whether taurine concentrations differ across preclinical myxomatous mitral valve disease (MMVD) stages or between CKCSs eating diets that meet World Small Animal Veterinary Association (WSAVA) nutritional guidelines versus other diets. ANIMALS: 200 privately owned CKCSs. PROCEDURES: Clinically healthy adult CKCSs were recruited prospectively. Diet and supplement history was collected. Dogs were staged by echocardiography using MMVD consensus guidelines. Taurine concentrations were measured in deproteinized lithium heparin WB and plasma samples with the postcolumn ninhydrin derivatization method on a dedicated amino acid analyzer. RESULTS: There were 12 stage A (6%), 150 stage B1 (75%), and 38 stage B2 (19%) CKCSs. Seventy-eight dogs (39%) were reported by their owners to be eating diets meeting WSAVA nutritional guidelines; 116 (58%) were not. Taurine concentrations in plasma (P = .444) and WB (P = .073) were not significantly different across MMVD stages or between CKCSs eating diets meeting WSAVA nutritional guidelines versus other diets (P = .345 and P = .527, respectively). Reference intervals for WB taurine (152 to 373 µM) and plasma taurine (51 to 217 µM) concentrations in CKCSs were generated. CLINICAL RELEVANCE: In CKCSs, taurine concentrations do not differ significantly based on preclinical MMVD stage, nor do they differ significantly based on consumption of a diet that does or does not meet WSAVA nutritional guidelines.

Asymptomatic Canine Degenerative Valve Disease: Diagnosis and Current and Future Therapies.

Degenerative valve disease (DVD) is the leading cause of heart disease and heart failure in the dog. The first consensus statement published in 2009 by the American College of Veterinary Internal Medicine was updated in 2019 and provides guidelines for the diagnosis and treatment of DVD. These updated guidelines recommend treatment with pimobendan in stage B2 DVD characterized by sufficient left heart enlargement. Asymptomatic dogs with DVD that do not meet or exceed the definition of stage B2 are considered stage B1. No treatment is recommended in stage B1 DVD. This article discusses the relevant scientific background and practical application of the updated DVD guidelines related to stage B. In addition, management of common sequelae of DVD that can result in clinical signs unrelated to congestive heart failure will be reviewed. The impact of new evidence on current recommendations and a glimpse into novel diagnostic approaches and possible future therapies will also be addressed.

Temporal changes in clinical and radiographic variables in dogs with preclinical myxomatous mitral valve disease: The EPIC study.

BACKGROUND: The Evaluation of pimobendan in dogs with cardiomegaly caused by preclinical myxomatous mitral valve disease (EPIC) study monitored dogs with myxomatous mitral valve disease (MMVD) as they developed congestive heart failure (CHF). OBJECTIVES: To describe the changes in clinical and radiographic variables occurring as dogs with MMVD and cardiomegaly develop CHF, compared to similar dogs that do not develop CHF. ANIMALS: One hundred and thirty-five, and 73 dogs that did or did not develop CHF, respectively. MATERIALS AND METHODS: The following variables were evaluated in 2 groups of dogs (dogs that did or did not develop CHF): Heart rate (HR), clinic respiratory rate (RR), home-measured resting respiratory rate (RRR), rectal temperature (RT), body weight (BW), and vertebral heart sum (VHS). Absolute value and rate of change of each variable were calculated for each day a dog was in study. Daily means were calculated and plotted against time. The onset of CHF or last visit before leaving the study were set as reference time points. RESULTS: The most extreme values and rate of change occurred in variables immediately before onset of CHF. Vertebral heart sum increased earliest. Heart rate, RR, and RRR also increased. Rectal temperature and BW decreased. Increases in RR and RRR were most extreme and occurred immediately before CHF. CONCLUSIONS AND CLINICAL IMPORTANCE: Dogs with MMVD and cardiomegaly experience increases in HR, RR, RRR, and VHS, and decreases in BW and RT as they develop CHF. The variables with highest absolute change and rate of change were RR and RRR. These findings reinforce the value of RR and RRR as indicators of impending or incipient CHF.

Long-term incidence and risk of noncardiovascular and all-cause mortality in apparently healthy cats and cats with preclinical hypertrophic cardiomyopathy.

BACKGROUND: Epidemiologic knowledge regarding noncardiovascular and all-cause mortality in apparently healthy cats (AH) and cats with preclinical hypertrophic cardiomyopathy (pHCM) is limited, hindering development of evidence-based healthcare guidelines. OBJECTIVES: To characterize/compare incidence rates, risk, and survival associated with noncardiovascular and all-cause mortality in AH and pHCM cats. ANIMALS: A total of 1730 client-owned cats (722 AH, 1008 pHCM) from 21 countries. METHODS: Retrospective, multicenter, longitudinal, cohort study. Long-term health data were extracted by medical record review and owner/referring veterinarian interviews. RESULTS: Noncardiovascular death occurred in 534 (30.9%) of 1730 cats observed up to 15.2 years. Proportion of noncardiovascular death did not differ significantly between cats that at study enrollment were AH or had pHCM (P = .48). Cancer, chronic kidney disease, and conditions characterized by chronic weight-loss-vomiting-diarrhea-anorexia were the most frequently recorded noncardiovascular causes of death. Incidence rates/risk of noncardiac death increased with age in AH and pHCM. All-cause death proportions were greater in pHCM than AH (65% versus 40%, respectively; P < .001) because of higher cardiovascular mortality in pHCM cats. Comparing AH with pHCM, median survival (study entry to noncardiovascular death) did not differ (AH, 9.8 years; pHCM, 8.6 years; P = .10), but all-cause survival was significantly shorter in pHCM (P = .0001). CONCLUSIONS AND CLINICAL IMPORTANCE: All-cause mortality was significantly greater in pHCM cats due to disease burden contributed by increased cardiovascular death superimposed upon noncardiovascular death.

Asymptomatic Canine Degenerative Valve Disease: Current and Future Therapies.

Degenerative valve disease (DVD) is the leading cause of heart disease and congestive heart failure (CHF) in the dog. The first published consensus statement provided guidelines for the diagnosis and treatment of DVD. Although treatment was not recommended in stage B1 DVD, consensus was not reached regarding evidence-based recommendations for treatment of stage B2 DVD. This article addresses the impact of new evidence on historical recommendations for stage B DVD and gives the reader a glimpse into possible future therapies. Management of common sequelae of DVD that can result in clinical signs that are not attributable to CHF is also discussed.

Biologic variability of cardiac troponin I in healthy dogs and dogs with different stages of myxomatous mitral valve disease using standard and high-sensitivity immunoassays.

BACKGROUND: Biologic variability (BV) is one aspect of interpreting changes in biomarker concentrations known to be clinically important in people with cardiac disease, but it has not been adequately addressed in dogs so far. OBJECTIVES: The purpose of the study was to determine BV of cardiac troponin I (cTnI) in healthy dogs and dogs with 3 stages of myxomatous mitral valve disease (MMVD). METHODS: Healthy dogs and dogs with 3 stages of MMVD were prospectively assigned to groups based on comprehensive clinical evaluation using current guidelines. Concentrations of cTnI were measured hourly, daily, and weekly using standard and high-sensitivity immunoassays. Within- (CVI ) and between-subject (CVG ) coefficients of variability, percent reference change value (RCV), and index of individuality (IoI) were calculated. RESULTS: All 10 healthy dogs and 76/112 (68%) of samples from 28 MMVD dogs had cTnI concentrations below the limit of detection (LOD) using a standard sensitivity immunoassay. Only 49/160 (31%) of healthy dog samples and no MMVD samples had cTnI below the high-sensitivity immunoassay LOD. Data analysis for the high-sensitivity immunoassay revealed CVI of 48.1%, CVG of 60.1%, RCV of 134.0%, and IoI of 0.804 in healthy dogs. In MMVD dogs, CVI was 39.6%, CVG was 80.7%, RCV was 110%, and IoI was 0.494. Of all MMVD dogs, those with Stage B2 had the lowest RCV of 91%. CONCLUSIONS: Biologic variability affects cTnI concentrations in healthy dogs and dogs with MMVD. Consideration of BV may be clinically relevant when monitoring individual changes in cTnI values, using high-sensitivity immunoassays.

Biologic variability of N-terminal pro-brain natriuretic peptide in healthy dogs and dogs with myxomatous mitral valve disease.

INTRODUCTION: To determine the biologic variability of N-terminal pro-brain natriuretic peptide (NTproBNP) in healthy dogs and dogs with various stages of myxomatous mitral valve disease (MMVD). ANIMALS: Thirty-eight privately owned dogs: 28 with MMVD and 10 healthy controls. MATERIALS AND METHODS: Prospective clinical study with comprehensive evaluation used to group dogs as healthy or into three stages of MMVD based on current guidelines. NTproBNP was measured hourly, daily, and weekly. For each group, analytical (CVA), within-subject (CVI), and between-subject (CVG) coefficients of variability were calculated in addition to percent critical change value (CCV) and index of individuality (IoI). RESULTS: For healthy dogs, calculated NTproBNP values were: CVA = 4.2%; CVI = 25.2%; CVG = 49.3%; IoI = 0.52, and CCV = 70.8%. For dogs with MMVD, calculated NTproBNP values were: CVA = 6.2%; CVI = 20.0%; CVG = 61.3%; IoI = 0.34, and CCV = 58.2%. CONCLUSIONS: Biologic variability affects NTproBNP concentrations in healthy dogs and dogs with MMVD. Monitoring serial individual changes in NTproBNP may be clinically relevant in addition to using population-based reference ranges to determine changes in disease status.

Analytical validation and clinical evaluation of a commercially available high-sensitivity immunoassay for the measurement of troponin I in humans for use in dogs.

OBJECTIVE: To analytically validate a commercially available high-sensitivity immunoassay for measurement of cardiac troponin I (cTnI) in humans for use in dogs and to evaluate serum cTnI concentrations in healthy dogs and 3 well-defined groups of dogs with common cardiac diseases. ANIMALS: Canine serum samples were used for validation. 85 client-owned dogs including 24 healthy controls, 20 with myxomatous mitral valve disease, 19 with congenital heart disease, and 22 with arrhythmias. METHODS: Four serum samples were used to analytically validate the ADVIA Centaur TnI-Ultra assay by assessing intra-assay variability, inter-assay variability, spiking recovery, and dilutional parallelism. Dogs were grouped based on examination, echocardiography, and additional testing as clinically indicated, and serum cTnI concentrations were compared. RESULTS: Analysis of the serum samples used for validation revealed an intra-assay coefficient of variation between 3.6% and 5.7%, and an inter-assay coefficient of variation between 2.4% and 5.9%. Observed to expected ratios for spiking recovery were 97.9 ± 8.6% (mean, SD). Observed to expected ratios for dilutional parallelism were 73.0 ± 11.5% (mean, SD). Dogs with cardiac disease had significantly higher serum cTnI concentrations (P < 0.005) than healthy dogs. CONCLUSIONS: The ADVIA Centaur TnI-Ultra's low limit of detection allows measurement of serum cTnI in the majority of dogs even with no or mild cardiac disease. Dilution of samples for measurement of values above the upper limit of detection is not reliable and therefore not recommended. Serum cTnI concentrations are significantly higher in dogs with cardiac disease compared to healthy dogs.

Hybrid technique for ventricular septal defect closure in a dog using an Amplatzer® Duct Occluder II.

A left-to-right shunting muscular ventricular septal defect (VSD) was diagnosed in a 4-month-old, female, 1.8 kg Bichon Frise - poodle mix dog. Echocardiographic evidence of cardiac remodeling, calculated pulmonary blood flow (Qp) to systemic blood flow (Qs) ratio of 2.8, and radiographic evidence of pulmonary edema supported the diagnosis of a hemodynamically important VSD. Using a combination of surgery and interventional catheter-based techniques to approach the VSD through the right ventricle, the VSD was occluded with an Amplatzer(®) Duct Occluder (ADO) II device. The ADO II is a low profile, flexible device originally developed for patent ductus arteriosus closure in humans that has been used to close muscular and perimembranous VSD in children. This report describes the hybrid procedure and imaging that was essential for successful occlusion of the VSD in this dog.

Minimally invasive transxiphoid approach to the cardiac apex and caudoventral intrathoracic space.

OBJECTIVE: To describe a minimally invasive surgical technique for procedures involving the caudoventral compartment of the thoracic cavity. STUDY DESIGN: Case series. ANIMALS: Dogs (n = 13). METHODS: Thirteen dogs; undergoing epicardial pacemaker implantation (9), palliative pericardial window (2), perforated right ventricle repair with epicardial pacemaker implantation (1), and peritoneopericardial diaphragmatic hernia (1) were operated by a transxiphoid approach. Dogs were positioned in dorsal recumbency and the bony xiphoid process was dissected free of adjoining tissue and transected proximally and distally. The distal transection was proximal to the cartilaginous junction of the process and the diaphragm. Entry to the thoracic cavity without penetration of the abdomen provided access for surgical treatment. RESULTS: All dogs recovered without complication. No dogs required thoracostomy tube placement. CONCLUSIONS: Transxiphoid approach is minimally invasive and provides adequate exposure for disorders of the caudoventral thoracic cavity.

Outcome of minimally invasive surgical treatment of heartworm caval syndrome in dogs: 42 cases (1999-2007).

OBJECTIVE: To report the outcome of minimally invasive surgical treatment of heartworm caval syndrome in a series of dogs and to provide information on long-term survival of patients with this condition. DESIGN: Retrospective case series. ANIMALS: 42 client-owned dogs with a diagnosis of heartworm caval syndrome. PROCEDURES: Information on history, clinical, laboratory, and diagnostic imaging findings and treatment was obtained from medical records. When possible, additional follow-up information was obtained through telephone interviews with referring veterinarians and owners. RESULTS: Of the 42 dogs with caval syndrome, 21 underwent minimally invasive surgical treatment consisting of transvenous heartworm extraction. Two of the 21 dogs died during the procedure, and after surgery, 4 died. Following induction of anesthesia, heartworms migrated into the distal portion of the pulmonary artery in 1 dog; therefore, extraction was not attempted. Transvenous heartworm extraction was completed successfully in 14 dogs, and all 14 of these dogs were discharged from the hospital. Mean follow-up time in these 14 dogs was 24.4 +/- 17.7 months with a range of 2 to 56 months. At the time of final follow-up, 10 of these 14 dogs had survived at least 18 months and 7 had survived > 24 months. By the end of the study, 1 dog was lost to follow-up and 3 had been euthanatized for unrelated reasons. CONCLUSIONS AND CLINICAL RELEVANCE: Results of the study reported here suggest that dogs with caval syndrome that undergo successful transvenous heartworm extraction and survive to discharge have a good long-term prognosis.