David J. Connolly

Cardiac troponin I in cats with hypertrophic cardiomyopathy

The molecular structure of cardiac troponin I (cTnI) is highly conserved across mammalian species and assays developed for its measurement in human patients have been validated in a number of veterinary species. A raised concentration of circulating cTnI is a sensitive and specific marker of cardiac myocyte injury. Raised levels have been documented in a variety of cardiac diseases in both human and veterinary patients. This study compared serum cTnI concentrations between 16 cats diagnosed with hypertrophic cardiomyopathy (HCM) using echocardiography and 18 control cats. The results show that cats with HCM have significantly higher concentration of serum cTnI (median 0.95 ng/ml, range 0.2–4.1 ng/ml) than control cats (median <0.2 ng/ml, range <0.2–0.25 ng/ml) [P<0.0001]. Furthermore in cats with cardiomyopathy a weak correlation was found between the thickness of the left ventricular freewall in diastole measured by ultrasound and serum cTnI concentration (r2=0.28;P=0.036). These results suggest that measurement of serum cTnI concentration may enable cats with cardiomyopathy to be distinguished from normal cats using the assay described here.

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.

Population characteristics and survival in 127 referred cats with hypertrophic cardiomyopathy (1997 to 2005)

OBJECTIVES To evaluate the characteristics and survival of a recent population of cats with hypertrophic cardiomyopathy. METHODS Records at the Royal Veterinary College Queen Mother Hospital for Animals were searched for cats diagnosed with hypertrophic cardiomyopathy between 1997 and 2005. Referring veterinarians and owners were contacted to determine survival times. RESULTS Cats with hypertrophic cardiomyopathy were evaluated for population characteristics (n=127) and survival times (n=109). Overall median survival from date of hypertrophic cardiomyopathy diagnosis at the Queen Mother Hospital for Animals was 1276 days. Cats with hypertrophic cardiomyopathy were younger (P=0·009), and more likely to be male (P<0·001) compared to a hospital control group (n=1473), and Ragdolls were over-represented (P<0·05). Characteristics associated with increased survival in univariate analysis included younger age (P=0·007), asymptomatic status (P<0·001), normal left atrial size (P<0·001) and presence of systolic anterior motion of the mitral valve (P=0·003). Systolic anterior motion was associated with asymptomatic status, and did not influence survival in asymptomatic cats or those in congestive heart failure. Age, left atrial size and breed were significantly associated with survival time in a multivariate analysis. CLINICAL SIGNIFICANCE Cats with hypertrophic cardiomyopathy and left atrial enlargement have a poorer prognosis. The positive influence of systolic anterior motion on survival is likely to be linked to its association with asymptomatic status.

Prognostic Indicators in Cats with Hypertrophic Cardiomyopathy

BACKGROUND Left atrial (LA) enlargement, congestive heart failure (CHF), and aortic thromboembolism (ATE) are associated with decreased survival in cats with hypertrophic cardiomyopathy (HCM), but the prognostic value of echocardiographic variables has not been well characterized. HYPOTHESIS/OBJECTIVES We hypothesized that LA echocardiographic variables and assessment of left ventricular (LV) diastolic and systolic function would have prognostic value in cats with HCM. ANIMALS Two hundred eighty-two cats diagnosed with HCM. METHODS Clinical and echocardiographic records of affected cats seen at the Royal Veterinary College from 2004 to 2009 were retrospectively analyzed. Only cats with echocardiographic confirmation of LV diastolic wall thickness ≥ 6 mm were included. Outcomes were obtained from clinical records or referring veterinarians and owners. RESULTS Deaths occurred in 164 cats, of which 107 were believed to have been cardiac deaths. Univariable predictors of an increased risk of cardiac death included older age, absence of a murmur, presence of a gallop sound or arrhythmia, presentation with either CHF or ATE, extreme LV hypertrophy (≥ 9.0 mm), LV fractional shortening (FS%) ≤ 30%, regional wall hypokinesis, increased left atrial size, decreased left atrial function, spontaneous echo-contrast/thrombus or both, absence of left ventricular outflow tract obstruction, and a restrictive diastolic filling pattern. Coxs proportional hazard analysis identified LA dysfunction, low LV systolic function, and extreme LV hypertrophy as independent predictors of decreased cardiac survival time. CONCLUSIONS AND CLINICAL IMPORTANCE Echocardiographic measurement of LA function, extreme LV hypertrophy, and LV systolic function provides important prognostic information in cats with HCM.

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

OBJECTIVES To determine if serum natriuretic peptide (NP) concentrations could distinguish cardiac from non-cardiac causes of respiratory distress (RD) in cats. ANIMALS Seventy-four cats from 1 university hospital were used. METHODS Serum 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). RESULTS RD-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. CONCLUSIONS Serum 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.

Serum troponin I levels in hyperthyroid cats before and after treatment with radioactive iodine.

A raised concentration of serum cardiac troponin I (cTnI) is a sensitive marker of cardiac myocyte injury in the cat and assays developed for its measurement in human patients have been validated in the cat. Raised levels have been associated with a number of cardiac insults including hypertrophic cardiomyopathy and trauma. Hyperthyroidism is a common disease of older cats and excess thyroid hormone is known to produce significant cardiovascular effects in this species. This study evaluated the effect of treatment for hyperthyroidism with radioactive iodine on cTnI concentration, assessed the association between thyroxin levels and glomerular filtration rate (GFR) and cTnI concentration in cats treated for hyperthyroidism and described changes in echocardiographic parameters following treatment. Prior to the treatment serum cTnI was measured and echocardiography performed, thyroxin, cTnI, and echocardiography were then repeated at various time points following radioisotope therapy. The results show that higher thyroxin levels were significantly (P=0.002) associated with a higher likelihood of the cat presenting with detectable levels of cTnI. No significant association was found between GFR and presence of detectable levels of cTnI. Furthermore the results indicate that the effects of hyperthyroidism on echocardiographic parameters appear considerably less in this study than in previous studies and that the main outcome of treatment on these parameters is a significant reduction in fractional shortening (P=0.006). These results suggest that chronic exposure to excess thyroid hormone may induce myocyte damage of sufficient severity to raise serum cTnI concentration in a proportion of cats that resolves following establishment of a euthyroid state.

Plasma concentrations of natriuretic peptides in normal cats and normotensive and hypertensive cats with chronic kidney disease.

OBJECTIVES To determine if natriuretic peptide concentrations are increased in cats with systemic hypertension and/or chronic kidney disease (CKD). ANIMALS 22 normal cats, 13 normotensive cats with mild-moderate CKD (NT-CKD), 15 hypertensive cats with mild-moderate CKD (HT-CKD) and 8 normotensive cats with severe CKD (NT-CKD-severe). METHODS N-terminal pro-B-type (NT-proBNP) and pro-A-type (NT-proANP) natriuretic peptides were measured in plasma samples from all cats using commercially available assays and concentrations in the normal and diseased groups compared using non-parametric statistical tests. Spearmans rank correlation was used to test for an association between natriuretic peptide and creatinine concentrations. RESULTS NT-proANP was significantly higher in the NT-CKD-severe than the normal group of cats (P=0.006) but there were no other differences between groups. NT-proBNP concentrations were significantly higher in the HT-CKD group than both the normal (P<0.001) and the NT-CKD (P<0.001) groups. NT-proBNP concentrations were also higher in the NT-CKD-severe (P<0.001) and the NT-CKD (P=0.005) groups than the normal group. NT-proANP but not NT-proBNP was significantly and positively associated with plasma creatinine concentration. CONCLUSIONS Measurement of NT-proBNP shows promise as a diagnostic marker for systemic hypertension in the cat. Its concentration is not significantly increased in cats with mild-moderate normotensive CKD.

Double Chambered Right Ventricle in 9 Cats

BACKGROUND Double-chambered right ventricle (DCRV) is a frequently recognized cardiac congenital abnormality in humans. It has been described in dogs and in 1 cat. However systemic description of clinical and echocardiographic features of the disease in cats is currently lacking from the veterinary literature. ANIMALS Nine cats with DCRV are described. RESULTS The cats ranged from 4 months to 10 years of age. Eight cats at presentation were asymptomatic and 1 cat had chylothorax. In all cases echocardiography revealed abnormal fibromuscular bundles obstructing the mid-right ventricle, dividing the chamber into 2 compartments. The proximal right ventricular compartment was markedly hypertrophied, and right atrial dilation was usually present. The mean pressure gradient measured across the stenotic area was 130 +/- 50 mm Hg. Concurrent abnormalities included a ventricular septal defect (n = 2); aortic malalignment, aortic insufficiency (n = 1); and congenital peritoneal-pericardial diaphragmatic hernia (n = 1). Two cats had systolic anterior motion of the mitral valve, one of which had concurrent left ventricular hypertrophy. Five cats have remained asymptomatic for a median period of 3.6 years (range, 3.3-5 years) and 3 cats have developed clinical signs associated with congestive heart failure (at 2, 3.3, and 9 years). One cat showed progressive lethargy and exercise intolerance and underwent partial ventriculectomy at the age of 2 years. This cat died during the operation with electromechanical dissociation. CONCLUSIONS DCRV is a congenital cardiac abnormality that may be more common than previously recognized.

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.

Seizure-Like Episodes in 3 Cats with Intermittent High-Grade Atrioventricular Dysfunction

Reliance on history and description of episodes of collapse to differentiate seizures from syncope can be misleading. Syncope can have features of seizures or can be the cause of seizures. Clinical and neurologic examinations can also be misleading. High-grade atrioventricular (AV) block can be intermittent in cats and interictal neurologic examination can be normal in patients with epilepsy. In this report we describe highgrade AV dysfunction that mimicked epilepsy in 3 cats.