Sudden death associated with QT interval prolongation and KCNQ1 gene mutation in a family of English Springer Spaniels.

BACKGROUND: A 5-year-old, healthy English Springer Spaniel died suddenly 4 months after delivering a litter of 7 puppies. Within 4 months of the dam's death, 3 offspring also died suddenly. HYPOTHESIS: Abnormal cardiac repolarization, caused by an inherited long QT syndrome, is thought to be responsible for arrhythmias leading to sudden death in this family. ANIMALS: Four remaining dogs from the affected litter and 11 related dogs. METHODS: Physical examination and resting ECG were done on the littermates and 9 related dogs. Additional tests on some or all littermates included echocardiogram with Doppler, Holter monitoring, and routine serum biochemistry. Blood for DNA sequencing was obtained from all 15 dogs. RESULTS: Three of 4 littermates examined, but no other dogs, had prolonged QT intervals with unique T-wave morphology. DNA sequencing of the KCNQ1 gene identified a heterozygous single base pair mutation, unique to these 3 dogs, which changes a conserved amino acid from threonine to lysine and is predicted to change protein structure. CONCLUSIONS AND CLINICAL IMPORTANCE: This family represents the first documentation in dogs of spontaneous familial QT prolongation, which was associated with a KCNQ1 gene mutation and sudden death. Although the final rhythm could not be documented in these dogs, their phenotypic manifestations of QT interval prolongation and abnormal ECG restitution suggested increased risk for sudden arrhythmic death. The KCNQ1 gene mutation identified is speculated to impair the cardiac repolarizing current IKs, similar to KCNQ1 mutations causing long QT syndrome 1 in humans.

Myocardial toxicity in a group of greyhounds administered ractopamine.

Ractopamine, a synthetic ß(2)-adrenoceptor agonist, is widely used as a feed additive in the United States to promote a reduction in body fat and enhance muscle growth in cattle, pigs, and turkeys. It has the potential for illegal use in show and racing animals because it may affect performance via its ß-adrenergic agonist properties or anabolic activities. Nine greyhounds were orally administered 1 mg/kg of ractopamine to investigate the ability to detect the drug in urine. Postdosing, 7 of 9 dogs developed cardiac arrhythmias and had elevated troponin levels indicating myocardial damage. One dog necropsied 4 days postdosing had massive myocardial necrosis, mild to focally moderate skeletal muscle necrosis, and widespread segmental arterial mediolysis. A second dog necropsied 17 days postdosing had mild myocardial necrosis and fibrosis. Scattered arteries exhibited segmental medial and perimedial fibromuscular dysplasia. This is the first reported case of arterial, cardiac, and skeletal muscle damage associated with ractopamine.

Retrospective evaluation of occlusion of patent ductus arteriosus with hemoclips in 20 dogs.

Twenty dogs with patent ductus arteriosus occluded with Hemoclips were evaluated with a mean follow-up time of 799.4 days (range, 83 to 3,580 days). Significant decreases were found between pre- and postsurgical means for vertebral heart size and for echocardiographic left atrial/aortic-root ratios and percent fractional shortening (%FS). Despite a good clinical outcome, six of 20 dogs had persistent cardiomyopathy of overload with diminished %FS (28% or less) at follow-up. One dog had residual ductal flow identified five days postoperatively. Subsequent evaluations in this case at 60, 144, 226, 344, and 560 days postoperatively demonstrated gradually diminishing ductal flow. The remaining 19 dogs did not recanalize.

Duration of the QT interval in healthy cats.

OBJECTIVE: To develop a clinically useful model for predicting QT interval duration as a function of heart rate in healthy cats. ANIMALS: 20 healthy cats. PROCEDURE: For all cats, results of a physical examination, electrocardiography, and echocardiography were normal. Twenty-four hour heart rate and rhythm data were collected by means of ambulatory electrocardiography. Hourly ECG segments were obtained from the 24-hour recordings. Mean heart rate and the mean of 5 QT interval measurements were calculated for each of 479 usable ECG segments. Analysis of covariance was used to develop models to describe variability in QT interval duration. RESULTS: Prediction equations (R2 = 0.81) including terms for heart rate, (heart rate)2, age group (1 to 4 vs 8 to 14 years old), and their interactions were developed. Sex, individual cat, and time of day were of little value in predicting QT interval duration. A simplified prediction equation without age group (R2 = 0.71) also was developed and had better predictive ability than reported correction formulas for QT interval duration. CONCLUSIONS AND CLINICAL RELEVANCE: Prediction equations with 95% prediction intervals for expected QT interval duration in healthy cats were generated. Abnormal QT interval duration can be associated with cardiac electrical instability, yet QT interval duration is greatly influenced by heart rate. Results of the present study provide reference ranges for expected QT interval duration as a function of heart rate in healthy cats.

Twenty-four-hour ambulatory electrocardiography in normal cats.

Twenty-four-hour ambulatory electrocardiograms were recorded in two age groups of 10 normal cats each: group 1 (1 to 4 years) and group 2 (8 to 14 years), with equal numbers of males and females in each group. Average heart rates over the 24-hour recording period ranged from 114 to 202 beats/minute (bpm). The mean 24-hour average rate did not differ between group 1 and group 2 (157.6 vs. 156.3+/-5.3 bpm, respectively); however, females (both groups combined) had higher average heart rates than males (166.8 vs. 147.1+/-5.3 bpm, respectively). Females also had a higher mean minimum heart rate than males (116.9 vs. 96.5+/-4.2 bpm, respectively); but there were no gender or age group differences in maximum heart rate. Results of hourly analyses of average, minimum, and maximum heart rates were similar. Mean heart rates rose from mid-afternoon to about 9:00 PM and were lowest just after midnight. Although regular sinus rhythm predominated, periods of sinus arrhythmia were evident in most cats, especially in early morning hours. Supraventricular extrasystoles were uncommon. Isolated ventricular extrasystoles occurred more frequently in group 2 cats; multiform configuration was observed in both groups. Repetitive ventricular extrasystoles, which usually consisted of occasional couplets, occurred more frequently in group 2 cats. One older cat had 2 short runs of ventricular tachycardia. Another older cat appeared to have a recurrent accelerated idioventricular rhythm.

Cardiac tumors in dogs: 1982-1995.

A Veterinary Medical Database search from 1982 to 1995 identified 1,383 dogs with tumors of the heart from a total population of 729,265 dogs (0.19% incidence). Hemangiosarcoma (HSA) was the most common cardiac tumor identified. In the subset of dogs with specific histologic diagnoses, the number with HSA was almost 10-fold that of the 2nd most common tumor, aortic body tumor. Primary heart tumors were more common than cardiac metastases. When biologic behavior was noted, most heart tumors were classified as malignant. Cardiac tumors (excluding lymphoma) occurred most often in dogs between the ages of 7 and 15 years. In very old dogs (>15 years), the frequency of cardiac tumors was the same or lower than that of the youngest age group. Tumors occurred with similar frequency in males and females, but the relative risk for spayed females was >4 times that for intact females. For HSA, spayed females had >5 times greater relative risk than did intact females. The risk for castrated males was slightly greater than that for intact males, which had 2.4 times the relative risk of intact females. Thus, neutering appeared to increase the risk of cardiac tumor in both sexes. Intact females were least likely to develop a cardiac tumor, whereas spayed females were most likely to develop a tumor. Twelve breeds had greater than average risk of developing a cardiac tumor, whereas 17 had lower risk.

Pharmacokinetics of atenolol in clinically normal cats.

OBJECTIVES: To determine the pharmacokinetics of atenolol (AT) after i.v. and oral administrations in cats, to assess duration of beta-blocking effect, and to determine whether AT can be effectively used once per day. ANIMALS: 9 clinically normal cats. PROCEDURE: Single doses of 1 (i.v.) or 3 (oral) mg of AT/kg of body weight were administered to each cat on different occasions, and serial blood samples were collected. Plasma concentrations of AT were subsequently determined, using high-performance liquid chromatography. The plasma concentration data were analyzed, using noncompartmental analysis. An isoproterenol challenge test was used to determine the beta-blocking effect of AT on heart rate after 3 consecutive days of oral treatment (3 mg/kg, once a day). RESULTS: After i.v. administration, mean +/- SD apparent volume of distribution at steady state and systemic clearance values were 1,088 +/- 148 ml/kg and 259 +/- 72 ml/h/kg, respectively. Bioavailability was 90 +/- 9% after oral administration. The half-life values were 3.44 +/- 0.5 and 3.66 +/- 0.39 hours after i.v. and oral administrations, respectively. Compared with baseline values prior to AT administration, heart rates at 6 and 12 hours after administration of AT were significantly reduced. CONCLUSIONS: AT has high oral bioavailability in cats, resulting in small interindividual variability in its kinetics in this species. The drug has beta-blocking effect in cats, as indicated by the attenuated heart rate response to isoproterenol; this effect persists for at least 12 hours in clinically normal cats.

Mitral stenosis in 15 dogs.

Mitral stenosis was diagnosed in 15 young to middle-aged dogs. There were 5 Newfoundlands and 4 bull terriers affected, suggesting a breed predisposition for this disorder. Clinical signs included cough, dyspnea, exercise intolerance, and syncope. Soft left apical diastolic murmurs were heard only in 4 dogs, whereas 8 dogs had systolic murmurs characteristic of mitral regurgitation. Left atrial enlargement was the most prominent radiographic feature. Left-sided congestive heart failure was detected by radiographs in 11 dogs within 1 year of diagnosis. Electrocardiographic abnormalities varied among dogs and included atrial and ventricular enlargement, as well as atrial and ventricular arrhythmias. Abnormalities on M-mode and two-dimensional echocardiograms included abnormal diastolic motion of the mitral valve characterized by decreased leaflet separation, valve doming, concordant motion of the parietal mitral valve leaflet, and a decreased E-to-F slope. Increased mitral valve inflow velocities and prolonged pressure half-times were detected by Doppler echocardiography. Cardiac catheterization, performed in 8 dogs, documented a diastolic pressure gradient between the left atrial, pulmonary capillary wedge, or pulmonary artery diastolic pressures and the left ventricular diastolic pressure. Necropsy showed mitral stenosis caused by thickened, fused mitral valve leaflets in 5 dogs and a supramitral ring in another dog. The outcome in affected dogs was poor; 9 of 15 dogs were euthanatized or died by 2 1/2 years of age.

Effects of amiodarone on myocardial performance in normal canine hearts and canine hearts with infarcts.

The effects of IV administered amiodarone, a class-III antiarrhythmic agent, on myocardial contractility, early myocardial relaxation, and hemodynamic variables were evaluated in normal canine hearts and those with infarcts. In the normal canine heart, amiodarone had important, but relatively mild, depressant effects on left ventricular contractility (assessed by maximal positive first derivative of left ventricular pressure (+dP/dtmax) and maximal elastance (Emax)) and heart rate when given IV at a dose of 10 mg/kg of body weight. An effect on contractility or active relaxation (assessed by maximal negative first derivative of left ventricular pressure (-dP/dtmax) and the time constant of isovolumic pressure decrease) was not identified with smaller doses. Myocardial infarction itself caused a predictable and marked depressant effect on myocardial contractility, as indicated by decreases in +dP/dtmax, ejection fraction, Emax, and -dP/dtmax, and elevation in end diastolic pressure. Additional depressive effects on contractility and active relaxation resulted when 10 mg of amiodarone/kg was administered to dogs with myocardial infarction and these effects were sufficient to worsen acute myocardial infarction-induced heart failure. Significant changes attributable to heart rate alone could not be identified. On the basis of our findings, we suggest that amiodarone administered IV should be used with caution in dogs with compromised ventricular function.

Sympathetic activation in dogs with congestive heart failure caused by chronic mitral valve disease and dilated cardiomyopathy.

Baseline plasma norepinephrine (NE) and epinephrine (EPI) concentrations were measured in dogs with naturally acquired heart failure (HF) caused by either degenerative mitral valve disease and mitral regurgitation (MR) or idiopathic dilated cardiomyopathy (DCM). Compared with controls (clinically normal), dogs with HF had increased plasma NE concentration, which was correlated positively with clinical severity of HF. Dogs with the most severe degree of HF (New York Heart Association functional class IV) had mean NE concentration significantly (P less than 0.05) greater than that of dogs with all other functional classes of HF. Overall, mean NE concentration in dogs with DCM was greater than that in dogs with MR. Plasma EPI concentration was not different between control dogs and dogs with HF or between dogs with DCM or MR. Correlations were not found between the echocardiographically derived end systolic volume index (used as an estimate of myocardial function) and plasma NE and EPI concentrations or serum sodium or potassium concentration. Dogs with DCM, as a group, had a small but significant (P less than 0.05) decrease in serum sodium concentration, compared with dogs with MR. This difference was maintained only for class-IV HF when dogs were separated according to functional HF class. In dogs with DCM, significant inverse correlation was found between plasma NE and serum sodium concentrations. When grouped together, all dogs with HF maintained this relationship; however, dogs with MR did not have correlation between plasma NE and serum sodium concentrations. Plasma EPI and serum sodium concentrations were not correlated for any group. It was concluded that in dogs, plasma NE, but not EPI, concentration is high in relation to the clinical severity of naturally acquired HF.(ABSTRACT TRUNCATED AT 250 WORDS)

Intracardiac rhabdomyosarcoma in a dog.

Intracardiac rhabdomyosarcoma was diagnosed in a 14-month-old Golden Retriever referred for evaluation of syncope. The dog was weak, with irregular heart rate, pulse deficit, heart murmur, and hepatomegaly. Thoracic radiography revealed generalized cardiomegaly, and electrocardiography revealed sinus rhythm with multiform ventricular premature complexes and intermittent ventricular tachycardia. Two-dimensional echocardiography revealed extensive soft-tissue density masses in both ventricles. An intracardiac neoplasm seen at postmortem examination was identified histologically as rhabdomyosarcoma, an uncommon intracardiac tumor in dogs.

Arterial thromboembolic disease in a dog with blastomycosis localized in a hilar lymph node.

An 8-year-old mixed-breed dog was evaluated for caudal paresis. Transient lameness of the left hind and left forelimbs had developed during the preceding week. Clinical findings included conscious proprioceptive deficits, hyporeflexive tendon reflexes and decreased pain perception, coolness in the hind limbs and left forelimb, and absence of femoral pulses. A fluid-dense mass was radiographically identified adjacent to the left atrium. Echocardiography revealed a mass in the left atrium and spontaneous contrast in the left ventricular lumen and aortic root. The dog was euthanatized because of its deteriorating condition. A large mass was adhered to the dorsal left atrial wall and had eroded into the atrial lumen. A sterile blood clot was attached to this site, and sterile thrombi were in the terminal portion of the aorta. Histologically, the mass was found to be hilar lymph node with chronic pyogranulomatous inflammation containing organisms characteristic of Blastomyces dermatitidis.

Chylothorax associated with congestive cardiomyopathy in a cat.

Chylothorax associated with congestive cardiomypathy was diagnosed in a 10-year-old male castrated domestic shorthair cat via analysis of pleural fluid. The triglyceride concentration in the pleural fluid was high (579 mg/dl), compared with that in serum (87 mg/dl), and the fluid cleared with ether. Evidence of atrial and left ventricular enlargement was found via electrocardiography and thoracic radiography. Left-sided cardiac dilatation and reduced systolic motion of the left ventricle were revealed by echocardiography. The cat was treated with digoxin, furosemide, and aspirin. Two months after initiation of treatment, fluid (265 ml) was aspirated from the pleural cavity. Two months after this procedure, the cat was doing well, with minimal pleural fluid production.

Echocardiographic diagnosis of pulmonic valve vegetative endocarditis in a cow.

A 5-year-old cow developed signs of bacterial endocarditis subsequent to parturition and mastitis. Massive vegetative lesions on the pulmonic valve were imaged with 2-dimensional echocardiography.

Atypical portosystemic shunt in a cat.

An adult cat with vague signs of gastrointestinal dysfunction was found to have a congenital portosystemic shunt. There were no signs of hepatoencephalopathy, which is in contrast to what has been reported in other cats with the disease.