Cardiac Troponin I and T as Prognostic Markers in Cats with Hypertrophic Cardiomyopathy

Background

Myocardial injury detected by cardiac troponin I and T (cTnI and cTnT) in cardiac disease is associated with increased risk of death in humans and dogs.

Hypothesis

Presence of myocardial injury predicts long‐term death in cats with hypertrophic cardiomyopathy (HCM), and ongoing myocardial injury reflects change in left ventricular wall thickness over time.

Animals

Thirty‐six cats with primary HCM.

Methods

Prospective cohort study. Cats with HCM were included consecutively and examined every 6 months. Echocardiography, ECG, blood pressure, and serum cTnI and cTnT were evaluated at each visit. Cox proportional hazards regression analysis was performed to evaluate prognostic potential of serum troponin concentrations at admission and subsequent examinations. Correlations were used to examine associations between troponin concentrations and cardiac hypertrophy.

Results

Troponin concentrations at admission were median [range] 0.14 [0.004–1.02] ng/mL for cTnI, and 13 [13–79.5] ng/L for cTnT. Both were prognostic for death (P = .032 and .026) as were the last available concentrations of each (P = .016 and .003). The final cTnT concentration was a significant predictor of death even when adjusting for the admission concentration (P = .043). In a model containing both markers, only cTnT remained significant (P = .043). Left ventricular free wall thickness at end‐diastole (LVFWd) at admission was correlated with cTnI at admission (r = 0.35, P = .035), however no significant correlations (r = 0.2–0.31, P = .074–.26) were found between changes in troponin concentrations and left ventricular thickness over time.

Conclusions and Clinical Importance

Myocardial injury is part of the pathophysiology leading to disease progression and death. Low sensitivities and specificities prevent outcome prediction in individual cats.     

Cardiac Troponins in Dogs and Cats

Cardiac troponins are sensitive and specific markers of myocardial injury. The troponin concentration can be thought of as a quantitative measure of the degree of injury sustained by the heart, however, it provides no information on the cause of injury or the mechanism of troponin release. Conventionally, the cardiac troponins have been used for diagnosis of acute myocardial infarction in humans and have become the gold standard biomarkers for this indication. They have become increasingly recognized as an objective measure of cardiomyocyte status in both cardiac and noncardiac disease, supplying additional information to that provided by echocardiography and ECG. Injury to cardiomyocytes can occur through a variety of mechanisms with subsequent release of troponins. Independent of the underlying disease or the mechanism of troponin release, the presence of myocardial injury is associated with an increased risk of death. As increasingly sensitive assays are introduced, the frequent occurrence of myocardial injury is becoming apparent, and our understanding of its causes and importance is constantly evolving. Presently troponins are valuable for detecting a subgroup of patients with higher risk of death. Future research is needed to clarify whether troponins can serve as monitoring tools guiding treatment, whether administering more aggressive treatment to patients with evidence of myocardial injury is beneficial, and whether normalizing of troponin concentrations in patients presenting with evidence of myocardial injury is associated with reduced risk of death.     

Plasma Cardiac Troponin I Concentration and Cardiac Death in Cats with Hypertrophic Cardiomyopathy

Background

The use of cardiac biomarkers to assist in the diagnosis of occult and symptomatic hypertrophic cardiomyopathy (HCM) in cats has been established. There is limited data describing their prognostic utility in cats with HCM.

Hypothesis

Circulating concentrations of N‐terminal B‐type natriuretic peptide (NTproBNP) and cardiac troponin I (cTnI) predict cardiac death in cats with HCM.

Animals

Forty‐one cats diagnosed with HCM at a veterinary teaching hospital, between February 2010 and May 2011.

Methods

Prospective investigational study. Plasma samples were collected from cats diagnosed with HCM and concentrations of NTproBNP and cTnI were analyzed at a commercial laboratory. Echocardiographic measurements from the day of blood sampling were recorded. Long‐term outcome data were obtained. Associations with time to cardiac death were analyzed using Cox proportional hazards models.

Results

When controlling for the presence/absence of heart failure and echocardiographic measures of left atrial size and function, cTnI > 0.7 ng/mL was independently associated with time to cardiac death. In univariable analysis, NTproBNP > 250 pmol/L was associated with cardiac death (P = .023), but this did not remain significant (P = .951) when controlling for the effect of clinical signs or left atrial size/function.

Conclusions and Clinical Importance

Plasma concentration of cTnI (cutoff >0.7 ng/mL) is a predictor of cardiac death in cats with HCM that is independent of the presence of heart failure or left atrial dilatation.     

Platelet Activation in Cats with Hypertrophic Cardiomyopathy

Background

Cats with hypertrophic cardiomyopathy (HCM) are at risk for development of systemic thromboembolic disease. However, the relationship between platelet activation state and cardiovascular parameters associated with HCM is not well described.

Objectives

To characterize platelet activation by flow cytometric evaluation of platelet P‐selectin and semiquantitative Western blot analysis of soluble platelet‐endothelial cell adhesion molecule‐1 (sPECAM‐1).

Animals

Eight normal healthy cats (controls) owned by staff and students of the School of Veterinary Medicine and 36 cats from the UC Davis Feline HCM Research Laboratory were studied.

Methods

Platelet‐rich plasma (PRP) was used for all flow cytometry studies. Platelet surface CD41 and P‐selectin expression were evaluated before and after ADP stimulation. sPECAM‐1 expression was evaluated by Western blot analysis of platelet‐poor plasma that had been stabilized with aprotinin. Standard echocardiographic studies were performed.

Results

Resting platelets from cats with severe HCM had increased P‐selectin expression compared to controls, and expressed higher surface density of P‐selectin reflected by their increased mean fluorescence intensities (MFI). Stimulation with ADP also resulted in significantly increased P‐selectin MFI of platelets from cats with severe HCM. Increased P‐selectin expression and MFI correlated with the presence of a heart murmur and end‐systolic cavity obliteration (ESCO). sPECAM‐1 expression from cats with moderate and severe HCM was significantly increased above those of control cats.

Conclusions and Clinical Importance

P‐selectin and sPECAM expression may be useful biomarkers indicating increased platelet activation in cats with HCM.     

猫肥厚型心肌病与心肌纤维化

肥厚型心肌病是猫最常见的原发性心脏疾病,典型特征为心脏左心室肥厚。心肌纤维化是猫肥厚型心肌病的标志性病理变化,其可导致心脏功能障碍和节律异常,是心肌病患猫预后不良的重要因素。对于猫肥厚型心肌病与心肌纤维化,目前缺乏针对性治疗,新型治疗方法亟需开发。本综述总结了猫肥厚型心肌病的病理特征以及目前关于猫心肌纤维化发病机制的研究进展,拟通过探索心肌纤维化的发病机制,从而为猫肥厚型心肌病新型治疗药物的开发寻找突破点。     

Field Safety and Efficacy of Protamine Zinc Recombinant Human Insulin for Treatment of Diabetes Mellitus in Cats

Background: This study describes the efficacy of a new protamine zinc recombinant human insulin (PZIR) preparation for treating diabetic cats. Objective: To evaluate effects of PZIR on control of glycemia in cats with newly diagnosed or poorly controlled diabetes mellitus. Animals: One hundred and thirty‐three diabetic cats 120 newly diagnosed and 13 previously treated. Methods: Prospective, uncontrolled clinical trial. Cats were treated with PZIR twice daily for 45 days. Control of glycemia was assessed on days 7, 14, 30, and 45 by evaluation of change in water consumption, frequency of urination, appetite, and body weight, serum fructosamine concentration, and blood glucose concentrations determined 1, 3, 5, 7, and 9 hours after administration of PZIR. Adjustments in dosage of PZIR were made as needed to control glycemia. Results: PZIR administration resulted in a significant decrease in 9‐hour mean blood glucose (199 ± 114 versus 417 ± 83 mg/dL, X± SD, P < .001) and serum fructosamine (375 ± 117 versus 505 ± 96 μmol/L, P < .001) concentration and a significant increase in mean body weight (5.9 ± 1.4 versus 5.4 ± 1.5 kg, P= .017) in 133 diabetic cats at day 45 compared with day 0, respectively. By day 45, polyuria and polydipsia had improved in 79% (105 of 133), 89% (118 of 133) had a good body condition, and 9‐hour mean blood glucose concentration, serum fructosamine concentration, or both had improved in 84% (112 of 133) of the cats compared with day 0. Hypoglycemia (<80 mg/dL) was identified in 151 of 678, 9‐hour serial blood glucose determinations and in 85 of 133 diabetic cats. Hypoglycemia causing clinical signs was confirmed in 2 diabetic cats. Conclusions and Clinical Relevance: PZIR is effective for controlling glycemia in diabetic cats and can be used as an initial treatment or as an alternative treatment in diabetic cats that do not respond to treatment with other insulin preparations.     

Evaluation of a Quality‐of‐Life Tool for Cats with Diabetes Mellitus

Background: Success in management of diabetes mellitus (DM) is defined as improvement of blood glucose concentrations and clinical signs. However, the psychological and social impact of DM and its daily treatment regimen on quality of life (QoL) of both animal and owner is uncertain. Hypothesis/Objectives: To design, validate, and apply a diabetic pet and owner‐centered, individualized measure of impact of DM (DIAQoL‐pet). Animals/Subjects: Two hundred and twenty‐one owners of insulin‐treated diabetic cats were recruited to complete the DIAQoL‐pet. Methods: Discussions and pilot surveys with clinicians and owners of diabetic cats led to the design of 29 specific DM‐associated QoL questions. Owners of diabetic cats completed the finalized survey. Each item was scored according to impact frequency and perceived importance. An item‐weighted impact score (IWIS) for each item was calculated, as was an average‐weighted impact score (AWIS) by averaging all IWISs. Principal component analysis and Cronbach's α calculation assessed the measure's reliability. Two overview questions measured overall QoL and diabetes‐dependent QoL. Results: The DIAQoL‐pet showed high reliability (Cronbach α 0.83). The AWIS was ?1.76 ± 2.4 (mean ± SD). Areas reported as most negatively impacting QoL included: “boarding difficulties” (IWIS ± SD: ?4.67 ± 5.3), “owner wanting more control” (?4.34 ± 4.7), “difficulties leaving cat with friends or family” (?4.21 ± 4.7), “worry” (?4.10 ± 3.9), “worry hypo” (?3.67 ± 3.5), “social life” (?3.48 ± 3.9), “costs” (?3.04 ± 3.8), and “work life” (?3.03 ± 3.7). Forty‐one percent of owners believed their cat's life would be “a little better” without DM. Conclusions and Clinical Importance: The DIAQoL‐pet proved robust and identified specific areas most negatively impacting on diabetic cats and their owners' QoL. This tool warrants further investigation for use in clinical or research settings.     

Analysis of 8 Sarcomeric Candidate Genes for Feline Hypertrophic Cardiomyopathy Mutations in Cats with Hypertrophic Cardiomyopathy

Background: Hypertrophic cardiomyopathy (HCM) is the most common heart disease in cats. Causative mutations have been identified in the Maine Coon (MC) and Ragdoll breed in the cardiac myosin binding protein C gene (MYBPC3). HCM is thought to be inherited in other breeds.
Hypothesis: That a causative mutation for HCM in the British Shorthair (BSH), Norwegian Forest (NWF), Siberian, Sphynx, or MC cats would be identified in the exonic and splice site regions of 1 of 8 genes associated with human familial HCM.
Animals: Three affected BSH, NWF, Siberians, Sphynx, 2 MC (without the known MC mutation), and 2 Domestic Shorthair cats (controls) were studied.
Methods: Prospective, observational study. Exonic and splice site regions of the genes encoding the proteins cardiac troponin I, troponin T, MYBPC3, cardiac essential myosin light chain, cardiac regulatory myosin light chain, α tropomyosin, actin, and β–myosin heavy chain were sequenced. Sequences were compared for nucleotide changes between affected cats, the published DNA sequences, and control cats. Changes were considered to be causative for HCM if they involved a conserved amino acid and changed the amino acid to a different polarity, acid-base status, or structure.
Results: A causative mutation for HCM was not identified, although several single nucleotide polymorphisms were detected.
Conclusions and Clinical Importance: Mutations within these cardiac genes do not appear to be the only cause of HCM in these breeds. Evaluation of additional cardiac genes is warranted to identify additional molecular causes of this feline cardiac disease.     

Relationship between Serum Symmetric Dimethylarginine Concentration and Glomerular Filtration Rate in Cats

Background

Direct measurement of glomerular filtration rate (GFR) is the preferred method to assess renal function in cats, but it is not widely used in the diagnosis of chronic kidney disease (CKD). In cats with CKD, symmetric dimethylarginine (SDMA) has been shown to increase and to correlate with plasma creatinine concentrations.

Hypothesis

In cats, reduced GFR corresponds with increased serum SDMA concentration.

Animals

The study group consisted of ten client‐owned cats whose GFR had been measured previously. Cats ranged in age from 11.1 to 16.9 years; both azotemic and nonazotemic animals were included.

Methods

Glomerular filtration rate was determined for each cat by plasma iohexol clearance using the three sample slope‐intercept method, and serum SDMA concentration was measured by liquid chromatography‐mass spectrometry.

Results

A linear relationship was observed between GFR and the reciprocal of serum SDMA concentration (R ² = 0.82, P < .001). A similar relationship was found between GFR and the reciprocal of plasma creatinine concentration (R ² = 0.81, P < .001).

Conclusions and Clinical Importance

Increased serum SDMA concentrations were observed in cats with reduced renal function as determined by direct measurement of GFR. This finding indicates that SDMA could have clinical applications in the diagnosis of CKD in cats.     

Remission of Diabetes Mellitus in Cats with Diabetic Ketoacidosis

Background: Diabetic ketoacidosis (DKA) has long been considered a key clinical feature of type‐1 diabetes mellitus (DM) in humans although. An increasing number of cases of ketoacidosis have been reported in people with type‐2 DM. Hypothesis/Objectives: Cats initially diagnosed with DKA can achieve remission from diabetes. Cats with DKA and diabetic remission are more likely to have been administered glucocorticoids before diagnosis. Animals: Twelve cats with DKA and 7 cats with uncomplicated DM. Methods: Retrospective case review. Medical records of cats presenting with DKA or DM were evaluated. Diabetic remission was defined as being clinically unremarkable for at least 1 month after insulin withdrawal. The cats were assigned to 1 of 3 groups: (1) cats with DKA and diabetic remission; (2) cats with DKA without diabetic remission; and (3) cats with DM and diabetic remission. Results: Seven cats with DKA had remission from diabetes. These cats had significantly higher concentrations of leukocytes and segmented neutrophils, and significantly lower concentrations of eosinophils in blood and had pancreatic disease more often than did cats with uncomplicated DM and diabetic remission. With regard to pretreatment, 3/7 cats in group 1, 1/5 cats in group 2, and 1/7 cats in group 3 had been treated with glucocorticoids. Conclusions and Clinical Importance: Remission of DM in cats presenting with DKA is possible. Cats with DKA and remission have more components of a stress leucogram, pancreatic disease, and seemed to be treated more often with glucocorticoids than cats with uncomplicated DM and diabetic remission.     

Predictors of Clinical Remission in Cats with Diabetes Mellitus

Background: Clinical remission is frequent in cats with well‐controlled diabetes mellitus, but few studies explored predictors of this phenomenon. Hypothesis: Data retrieved from medical records at admission might be valuable to identify likelihood of remission and its duration in diabetic cats. Animals: Ninety cats with newly diagnosed diabetes, followed‐up until death or remission. Methods: Retrospective cohort study. Data were collected from records at admission, including history, signalment, physical examination, haematology, and biochemical profile, and the occurrence and duration of remission, defined as normoglycemia without insulin for ≥4 weeks. Predictors of remission were studied with univariate and multivariate logistic regression. Factors associated with remission duration were analyzed with Kaplan‐Meier and Cox proportional hazard models. Results: Forty‐five (50%) cats achieved remission, after a median time of 48 days (range: 8–216). By study end, median remission duration was 114 days (range: 30–3,370) in cats that died and 151 days (range: 28–1,180) in alive cats. Remission was more likely with higher age (OR: 1.23, 95% CI: 1.04–1.46; P= .01) and less likely with increased serum cholesterol (OR: 0.36, 95% CI: 0.11–0.87; P= .04). Remission was longer with higher body weight (HR: 0.65, 95% CI: 0.42–0.99; P= .04) and shorter with higher blood glucose (HR: 1.01, 95% CI: 1.00–1.02; P= .02). Conclusions and Clinical Importance: Age, body weight, cholesterol, and glucose levels are suggested for prediction of remission or its duration in diabetic cats. Older cats developing diabetes may have a better outcome, possibly suggesting a slower disease progression.