N. Sydney Moïse

Utility of plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) to distinguish between congestive heart failure and non-cardiac causes of acute dyspnea in cats.

BACKGROUND Circulating plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration facilitates emergency diagnosis of congestive heart failure (CHF) in people. Its utility to discriminate between dyspneic cats with CHF vs. primary respiratory disease requires further assessment. Our objectives were to determine if NT-proBNP (1) differentiates dyspneic cats with CHF vs. primary respiratory disease; (2) increases with renal insufficiency; (3) correlates with left atrial dimension, radiographic cardiomegaly, and estimated left ventricular filling pressure (E/E(a)). METHODS NT-proBNP was measured in 167 dyspneic cats (66 primary respiratory disease, 101 CHF) to evaluate (1) relationship with clinical parameters; (2) ability to distinguish CHF from primary respiratory disease; (3) optimal cut-off values using receiver operating characteristic (ROC) curve analysis. RESULTS NT-proBNP (1) was higher (median and inter-quartile [25th-75th] percentile) in CHF (754 pmol/L; 437, 1035 pmol/L) vs. primary respiratory disease (76.5 pmol/L; 24, 180 pmol/L) cohorts (P<0.001); (2) positively correlated in CHF cats with increased inter-ventricular septal end-diastolic thickness (rho=0.266; P=0.007) and LV free wall thickness (rho=0.218; P=0.027), but not with radiographic heart size, left atrial size, left ventricular dimensions, E/E(a) ratio, BUN, creatinine, or thyroxine; (3) distinguished dyspneic CHF cats from primary respiratory disease at 265 pmol/L cut-off value with 90.2% sensitivity, 87.9% specificity, 92% positive predictive value, and 85.3% negative predictive value (area under ROC curve, 0.94). CONCLUSIONS NT-proBNP accurately discriminated CHF from respiratory disease causes of dyspnea.

Inherited ventricular arrhythmias and sudden death in German shepherd dogs

OBJECTIVES This report describes a unique group of German shepherd dogs with inherited ventricular arrhythmias and sudden death. Before death, these dogs have no evidence of cardiovascular failure. BACKGROUND There are few spontaneous animal models of sudden death that permit intensive investigation. METHODS To determine the temporal evolution of ventricular arrhythmias and to characterize the syndrome of sudden cardiac death in these dogs, 24-h ambulatory electrocardiographic (ECG) monitoring, echocardiograms, electrophysiologic testing and breeding studies were conducted. RESULTS The 24-h ambulatory ECGs from dogs that died showed frequent ventricular arrhythmias with rapid polymorphic ventricular tachycardia (rates > 480 beats/min). Affected dogs had a window of vulnerability for arrhythmias, with the highest incidence and severity of arrhythmias between 20 to 30 and 40 to 50 weeks of age. Affected dogs that died did not have prolongation of the QT interval over a spectrum of heart rates compared with unaffected dogs. The clinical arrhythmia was not induced in dogs during programmed electrical stimulation. Severely affected dogs monitored > 5 years did not develop any evidence of heart failure or cardiomyopathy, and no histopathologic abnormalities existed. Seventeen dogs died suddenly (age 4 to 30 months) and were either 1) found dead at first observation in the morning (n = 8), 2) observed to die during sleep (n = 4), 3) observed to die while resting after exercise (n = 3), or 4) observed to die during exercise (n = 2). All sudden deaths occurred between the end of September and April, with most (n = 11) during January and February. CONCLUSIONS The cause of the inherited severe ventricular arrhythmias and sudden death in these young German shepherd dogs is still undetermined. A purely arrhythmic disorder is supported by the lack of cardiac pathology. Moreover, the window of vulnerability to ventricular arrhythmias and the age and circumstances of death invite speculation about the role of the autonomic nervous system.

Dietary taurine deficiency and dilated cardiomyopathy in the fox

Taurine deficiency has been implicated as a potential cause of dilated cardiomyopathy. However, the relationship between taurine and myocardial function is presently unclear. The purpose of this study was to determine whether dilated cardiomyopathy in the fox is associated with dietary taurine deficiency. A total of 68 foxes from farms with a history of death caused by dilated cardiomyopathy and 14 foxes from a farm with no history of dilated cardiomyopathy were studied. Dilated cardiomyopathy was diagnosed by echocardiography in 48% of the foxes from one farm with a positive history and in none of the foxes from the control farm. Foxes less than 9 months of age were more commonly affected than older foxes (p = 0.03). Plasma taurine concentrations were significantly less (p less than 0.01) in foxes that had dilated cardiomyopathy (26.8 +/- 16.4 nmol/ml) than in the control foxes (99.3 +/- 60.2 nmol/ml). A significantly higher (p less than 0.01) incidence of dilated cardiomyopathy was present in foxes with a history of a sibling or offspring that died of dilated cardiomyopathy than in foxes without a family history of cardiac death. In one fox with dilated cardiomyopathy that was tested, the myocardial taurine concentration was lower (1.7 mumol/gm wet weight) than that of control foxes (7.3 +/- 1.6 mumol/gm wet weight). Hepatic cysteinesulfinic acid decarboxylase activity was significantly less (p less than 0.001) in foxes with dilated cardiomyopathy (0.97 +/- 0.2 nmol/mm.mg protein) than in control foxes (2.11 +/- 0.07 nmol CO2/mm.mg protein).(ABSTRACT TRUNCATED AT 250 WORDS)

Multicenter Evaluation of Plasma N-Terminal Probrain Natriuretic Peptide (NT-pro BNP) as a Biochemical Screening Test for Asymptomatic (occult) Cardiomyopathy in Cats

BACKGROUND B-type natriuretic peptide concentrations reliably distinguish between cardiac and respiratory causes of dyspnea, but its utility to detect asymptomatic cats with occult cardiomyopathy (OCM) is unresolved. HYPOTHESIS/OBJECTIVES Determine whether plasma N terminal probrain natriuretic peptide (NT-proBNP) concentration can discriminate asymptomatic cats with OCM from normal cats, and whether NT-proBNP concentration correlates with clinical, biochemical, and echocardiographic parameters. ANIMALS One hundred and fourteen normal, healthy cats; 113 OCM cats. METHODS Prospective, multicenter, case-controlled study. NT-proBNP was prospectively measured and cardiac status was determined from history, physical examination, and M-mode/2D/Doppler echocardiography. Optimal cut-off values were derived using receiver operating characteristic (ROC) curve analysis. RESULTS NT-proBNP was higher (median, interquartile range [25th and 75th percentiles]) in (1) OCM (186 pmol/L; 79, 478 pmol/L) versus normal (24 pmol/L; 24, 32 pmol/L) (P < .001); and (2) hypertrophic obstructive cardiomyopathy (396 pmol/L; 205, 685 pmol/L) versus hypertrophic cardiomyopathy (112 pmol/L; 48, 318 pmol/L) (P < .001). In OCM, NT-proBNP correlated (1) positively with LVPWd (ρ = 0.23; P = .01), LA/Ao ratio (ρ = 0.31; P < .001), LVs (ρ = 0.33; P < .001), and troponin-I (ρ = 0.64; P < .001), and (2) negatively with %FS (ρ = -0.27; P = .004). Area under ROC curve was 0.92; >46 pmol/L cut-off distinguished normal from OCM (91.2% specificity, 85.8% sensitivity); >99 pmol/L cut-off was 100% specific, 70.8% sensitive. CONCLUSIONS AND CLINICAL IMPORTANCE Plasma NT-proBNP concentration reliably discriminated normal from OCM cats, and was associated with several echocardiographic markers of disease severity. Further studies are needed to assess test performance in unselected, general feline populations, and evaluate relationships between NT-proBNP concentrations and disease progression.

Decreased Density of Ito in Left Ventricular Myocytes from German Shepherd Dogs with Inherited Arrhythmias

Decreased Ito in Dogs with Inherited Arrhythmias. Introduction: A colony of inbred German shepherd dogs with inherited ventricular arrhythmias has been established.

Morphology of Ventricular Arrhythmias in the Boxer as Measured by 12-Lead Electrocardiography with Pace-Mapping Comparison

The QRS amplitude and polarity were determined in 12-lead electrocardiograms recorded from 22 Boxers with ventricular arrhythmias. Eighty-one percent (18/22) of dogs displayed a positive QRS morphology in the caudoventral leads (II, III, and aVF) and 77% (17/22) of dogs displayed a positive QRS morphology in the left precordial leads (V2-V6). In leads I and V1, the polarity of the QRS complex was variable (positive or negative). To determine if these morphologic features were suggestive of ventricular complexes arising from the right or left ventricle, a comparison was made to the QRS complexes in a pace-mapping study performed in 7 healthy mixed-breed dogs. A total of 3 right and 4 left ventricular sites were paced. None of the left ventricular paced sites resulted in a QRS morphology similar to the most common spontaneous ventricular arrhythmia in the Boxers. In contrast, QRS morphology in each of the 3 right ventricular sites was similar to that observed in the Boxers (P < .033). Each of these produced positive deflections in the caudoventral and left precordial leads, but both positive and negative QRS complexes were observed in leads I and V1 only when the right ventricular septum was paced. This finding suggested that the right ventricular septum might be a site of origin for the ventricular rhythm observed in the Boxers because in the Boxers the polarity of leads I and V1 also varied. Pacing the right ventricular outflow tract always resulted in a negative QRS complex in lead 1, whereas pacing the right ventricular apex always resulted in a positive QRS complex in lead I and a negative QRS complex in V1. However, these locations cannot be excluded as possible sites of origin for the spontaneous ventricular arrhythmias in the Boxers because the arrhythmias could be originating from both of these locations. The spontaneous ventricular arrhythmia of the Boxer is most similar to that of paced ventricular rhythms arising from the right ventricle. More precise localization to a region of the right ventricle such as outflow tract, septal, or apical could not be made.

Abnormal cardiac repolarization and impulse initiation in German shepherd dogs with inherited ventricular arrhythmias and sudden death

OBJECTIVE We tested the hypothesis that delayed afterdepolarization (DAD)-associated rhythms in German shepherd dogs with reduced anteroseptal left ventricular (LV) sympathetic innervation derive from abnormal beta-adrenergic receptor effector coupling. METHODS AND RESULTS In anteroseptal LV midmyocardium of afflicted dogs, beta-receptor density was greater than that in normal dogs (P < .05), with affinity being equal in both groups. Basal and maximum isoproterenol (ISO) stimulated adenylyl cyclase activity of anteroseptal LV of afflicted dogs was greater than that in normal dogs (P < .05). Isolated anteroseptal M cell preparations of afflicted dogs studied with microelectrodes showed abnormal lengthening, rather than shortening of action potential duration in response to ISO, as well as a 61% incidence of 10(-7) mol/l ISO-induced triggered activity as compared to 12% in normals (P < .05). In contrast, there was no difference between afflicted and control dogs in triggered activity, beta-receptors or adenylyl cyclase activity in a normally innervated region of the ventricles. CONCLUSION In this model there is an increase in beta-receptor density and beta-adrenergic stimulation of adenylyl cyclase and of triggered activity in anteroseptal myocardium but not in a normally innervated region of the heart. Hence, abnormal beta-adrenergic signal transduction appears associated with the neural abnormality identified in dogs with inherited VT.

Estimation of heritabilities, genetic correlations, and breeding values of four traits that collectively define hip dysplasia in dogs

OBJECTIVE-To estimate heritabilities and genetic correlations among 4 traits of hip joints (distraction index [DI], dorsolateral subluxation [DLS] score, Norberg angle [NA], and extended-hip joint radiograph [EHR] score) and to derive the breeding values for these traits in dogs. ANIMALS-2,716 dogs of 17 breeds (1,551 dogs in which at least 1 hip joint trait was measured). PROCEDURES-The NA was measured, and an EHR score was assigned. Hip joint radiographs were obtained from some dogs to allow calculation of the DI and DLS score. Heritabilities, genetic correlations, and breeding values among the DI, DLS score, NA, and EHR score were calculated by use of a set of multiple-trait, derivative-free, restricted maximum likelihood computer programs. RESULTS-Among 2,716 dogs, 1,411 (52%) had an estimated inbreeding coefficient of 0%; the remaining dogs had a mean inbreeding coefficient of 6.21%. Estimated heritabilities were 0.61, 0.54, 0.73, and 0.76 for the DI, DLS score, NA, and EHR score, respectively. The EHR score was highly genetically correlated with the NA (r = -0.89) and was moderately genetically correlated with the DI (r = 0.69) and DLS score (r = -0.70). The NA was moderately genetically correlated with the DI (r = -0.69) and DLS score (r = 0.58). Genetic correlation between the DI and DLS score was high (r = -0.91). CONCLUSIONS AND CLINICAL RELEVANCE-Establishment of a selection index that makes use of breeding values jointly estimated from the DI, DLS score, NA, and EHR score should enhance breeding programs to reduce the incidence of hip dysplasia in dogs.

An Animal Model of Spontaneous Arrhythmic Death

Spontaneous Arrhythmic Death. Ventricular arrhythmias and the proclivity for sudden death have been identified in German shepherd dogs. This disorder is inherited, and affected animals can he consistently produced from an established colony. The arrhythmias are most prevalent in young dogs between 22 and 26 weeks of age, with death most frequent at this same age. Death occurs most frequently during presumed sleep or at rest after exercise or excitement. The QT interval is not prolonged; however, more frequent notching of the T wave exists in affected dogs compared to control dogs. Polymorphic rapid nonsustained ventricular tachycardia occurs most frequently following long RR intervals. Accordingly, perturhations that decrease the heart rate or enhance sinus arrhythmia increase the incidence of ventricular arrhythmias. Because the arrhythmias are age, behavior, and heart rate dependent, the autonomic nervous system may play a role in their generation. As determined by metaiodohenzylguanidine scintigraphy and immunocytochemical staining of tyrosine hydroxylase, cardiac sympathetic innervation is regionally deficient in affected dogs. Evidence suggests that initiation of the ventricular arrhythmias is caused by early after depolarization (EAD)‐induced triggered activity originating from left ventricular Purkinje fibers. Alpha1‐adrenergic stimulation provokes EADs in the Purkinje fibers and ventricular arrhythmias in the dogs. The development of EADs may be related to heterogeneity of repolarizing currents (Ito in particular) in affected dogs. From this canine model of spontaneous ventricular arrhythmias, the opportunity exists to investigate the interplay between abnormal development of cardiac innervation and the genesis of lethal ventricular arrhythmias.

Temporal organization of atrial activity and irregular ventricular rhythm during spontaneous atrial fibrillation: An in vivo study in the horse

Temporal Organization of Atrial Activity. Introduction: Atrial fibrillation (AF) is common in healthy horses. We studied the temporal organization of AF to test the hypothesis that the arrhythmia is governed by a high degree of periodicity and therefore is not random in the horse. Further, we surmised that concealed conduction of AF impulses in the AV node results in an inverse relationship between AF frequency and ventricular frequency.