A14-year-old 3.5-kg (7.7-lb) castrated male domestic shorthair cat was evaluated by the Neurology Service at the University of Florida Veterinary Medical Center because of a 2-month history of profound weakness, ataxia, head tremors, and suspected seizures. Approximately 1 year previously, a diagnosis of inflammatory bowel disease had been made at another veterinary hospital, which was controlled via administration of prednisolone (1.4 mg/kg [0.64 mg/lb], PO, q 12 h). One week before referral to the Veterinary Medical Center, a CBC revealed normochromic, normocytic, nonregenerative anemia (Hct, 27.9%; reference range, 30% to 48%) and a stress leukogram (WBC count, 29.2 × 103 cells/μL [reference range, 6.0 × 103 cells/μL to 10.0 × 103 cells/μL]; neutrophils, 26.1 × 103 cells/μL [reference range, 2.5 × 103 cells/μL to 12.5 × 103 cells/μL]; lymphocytes, 1.2 × 103 cells/μL [reference range, 1.5 × 103 cells/μL to 7.0 × 103 cells/μL]; monocytes, 1.9 × 103 cells/μL [reference range, 0 × 103 cells/μL to 0.8 × 103 cells/μL]; and eosinophils, 0.0 × 103 cells/μL [reference range, 0 × 103 cells/μL to 1.5 × 103 cells/μL]). Abnormalities detected via serum biochemical analyses included high hepatic enzyme activities (aspartate aminotransferase, 499 U/L [reference range, 0 to 60 U/L]; alanine aminotransferase, 564 U/L [reference range, 0 to 90 U/L]; and alkaline phosphatase, 525 U/L [reference range, 0 to 45 U/L]); high creatine kinase activity (2,701 U/L; reference range, 0 to 300 U/L); high total bilirubin concentration (0.6 mg/dL; reference range, 0 to 0.2 mg/dL); high cholesterol concentration (259 mg/dL; reference range, 95 to 175 mg/dL); and low phosphorus concentration (3.3 mg/dL; reference range, 4.0 to 6.6 mg/dL). Serum total thyroxine concentration was within reference limits (13.5 nmol/L; reference range, 12.3 to 35.7 nmol/L). At that prereferral evaluation, thoracic radiography, computed tomography of the head, and CSF analysis revealed no abnormalities; abdominal ultrasonography revealed a large hypoechoic liver, which was consistent with suspected hepatic lipidosis.
At the initial evaluation at the Veterinary Medical Center, results of a neurologic examination suggested that the cat was affected by both peripheral neuromuscular disease and CNS disease. The cat was anesthetized for magnetic resonance imaging, electrodiagnostic evaluation, and biopsy of the gastrocnemius muscle. After premedication with buprenorphine (0.025 mg/kg [0.011 mg/lb], IM), anesthesia was induced with propofol (7.0 mg/kg [3.2 mg/lb], IV) and maintained with inhaled sevoflurane at 0.5% to 1.5% in 100% oxygen. Magnetic resonance imaging did not reveal any intracranial abnormalities, but electromyographic findings were indicative of denervation; histologic examination of the gastrocnemius muscle biopsy specimen revealed evidence of a myopathy. During anesthesia, the cat developed profound hypothermia (minimum recorded rectal temperature, 32.8°C [91.0°F]) and became bradycardic; T-wave changes were evident on a lead II ECG trace. A consultation with a cardiologist was sought while the cat was still anesthetized. A grade 2/6 left parasternal systolic heart murmur was ausculted. Echocardiography revealed mild concentric hypertrophy of the left ventricle and mild mitral regurgitation, but the left atrium was apparently normal in size. Because serum thyroxine concentration (assessed 1 week earlier) and blood pressure (assessed during this initial evaluation) were within reference limits, these findings were considered consistent with mild hypertrophic cardiomyopathy.
ECG Interpretation
A 6-lead ECG was recorded during anesthesia when the cat's rectal temperature was 32.8°C (Figures 1 and 2). This initial ECG revealed sinus bradycardia (heart rate, 118 beats/min). The R-wave amplitude was mildly high at 1.1 mV (upper reference limit, 0.9 mV1), which is consistent with left ventricular hypertrophy. The QT interval was markedly prolonged (0.32 seconds; upper reference limit, 0.20 seconds1) even when corrected for heart rate with prediction intervals for healthy cats.2 Although the T waves maintained positive polarity, the T-wave amplitude alternated between 0.2 and 0.6 mV on a beat-to-beat basis. This was identified as isolated T-wave alternans because it was independent of changes in the QRS complex. Pulsus alternans resulting from mechanical alternans was not detected via digital palpation of the femoral pulses. Serum electrolyte concentrations were within reference limits.
Initial 6-lead ECG tracings obtained from a cat that had a 2-month history of profound weakness, ataxia, head tremors, and suspected seizures. The tracings were obtained during anesthesia when the cat's rectal temperature was 32.8°C (91.0°F). Sinus bradycardia (118 beats/min), large R-wave amplitude (1.1 mV), and prolonged QT interval (0.32 seconds) are evident. Notice the isolated T-wave alternans in which the T-wave amplitude alternates between 0.2 mV (small arrow) and 0.6 mV (large arrow). Paper speed = 50 mm/s; 10 mm = 1 mV.
Citation: Journal of the American Veterinary Medical Association 229, 1; 10.2460/javma.229.1.40
Initial 6-lead ECG tracings obtained from a cat that had a 2-month history of profound weakness, ataxia, head tremors, and suspected seizures. The tracings were obtained during anesthesia when the cat's rectal temperature was 32.8°C (91.0°F). Sinus bradycardia (118 beats/min), large R-wave amplitude (1.1 mV), and prolonged QT interval (0.32 seconds) are evident. Notice the isolated T-wave alternans in which the T-wave amplitude alternates between 0.2 mV (small arrow) and 0.6 mV (large arrow). Paper speed = 50 mm/s; 10 mm = 1 mV.
Citation: Journal of the American Veterinary Medical Association 229, 1; 10.2460/javma.229.1.40
Initial 6-lead ECG tracings obtained from a cat that had a 2-month history of profound weakness, ataxia, head tremors, and suspected seizures. The tracings were obtained during anesthesia when the cat's rectal temperature was 32.8°C (91.0°F). Sinus bradycardia (118 beats/min), large R-wave amplitude (1.1 mV), and prolonged QT interval (0.32 seconds) are evident. Notice the isolated T-wave alternans in which the T-wave amplitude alternates between 0.2 mV (small arrow) and 0.6 mV (large arrow). Paper speed = 50 mm/s; 10 mm = 1 mV.
Citation: Journal of the American Veterinary Medical Association 229, 1; 10.2460/javma.229.1.40
Serial lead II ECG traces recorded from the cat in Figure 1 during warming while recovering from anesthesia. Dark horizontal lines indicate QT intervals. A—Trace obtained when the cat's rectal temperature was 32.8°C (91.0°F) and heart rate was 118 beats/min; QT interval was 0.32 seconds. B—Trace obtained when the cat's rectal temperature was 34.8°C (94.7°F) and heart rate was 128 beats/min; QT interval was 0.26 seconds. C—Trace obtained when the cat's rectal temperature was 37.6°C (99.7°F) and heart rate was 158 beats/min; QT interval was 0.20 seconds. Notice that the T-wave alternans detectable in panel A is not evident in panels B and C. Paper speed = 50 mm/s; 10 mm = 1 mV.
Citation: Journal of the American Veterinary Medical Association 229, 1; 10.2460/javma.229.1.40
Serial lead II ECG traces recorded from the cat in Figure 1 during warming while recovering from anesthesia. Dark horizontal lines indicate QT intervals. A—Trace obtained when the cat's rectal temperature was 32.8°C (91.0°F) and heart rate was 118 beats/min; QT interval was 0.32 seconds. B—Trace obtained when the cat's rectal temperature was 34.8°C (94.7°F) and heart rate was 128 beats/min; QT interval was 0.26 seconds. C—Trace obtained when the cat's rectal temperature was 37.6°C (99.7°F) and heart rate was 158 beats/min; QT interval was 0.20 seconds. Notice that the T-wave alternans detectable in panel A is not evident in panels B and C. Paper speed = 50 mm/s; 10 mm = 1 mV.
Citation: Journal of the American Veterinary Medical Association 229, 1; 10.2460/javma.229.1.40
Serial lead II ECG traces recorded from the cat in Figure 1 during warming while recovering from anesthesia. Dark horizontal lines indicate QT intervals. A—Trace obtained when the cat's rectal temperature was 32.8°C (91.0°F) and heart rate was 118 beats/min; QT interval was 0.32 seconds. B—Trace obtained when the cat's rectal temperature was 34.8°C (94.7°F) and heart rate was 128 beats/min; QT interval was 0.26 seconds. C—Trace obtained when the cat's rectal temperature was 37.6°C (99.7°F) and heart rate was 158 beats/min; QT interval was 0.20 seconds. Notice that the T-wave alternans detectable in panel A is not evident in panels B and C. Paper speed = 50 mm/s; 10 mm = 1 mV.
Citation: Journal of the American Veterinary Medical Association 229, 1; 10.2460/javma.229.1.40
The cat was allowed to recover from anesthesia and rapidly warmed by use of a forced-air warming unit. Once the cat's rectal temperature was 34.8°C (94.7°F), another ECG trace was recorded (Figure 2). The heart rate increased to 128 beats/min, and the T-wave alternans resolved; the QT interval decreased to 0.26 seconds, which was still greater than the upper reference range limit1 but within the prediction interval (corrected for heart rate) for healthy cats.2 Rapid warming was continued, and a third ECG trace was recorded when the cat's rectal temperature was 37.6°C (99.7°F; Figure 2). This trace revealed a sinus rhythm at a rate of 158 beats/min and no T-wave alternans; the QT interval was 0.20 seconds, which was considered normal on the basis of reference range values1 and the prediction interval (corrected for heart rate) for healthy cats.2
Discussion
The T wave represents ventricular repolarization, and the QT interval represents the total duration of ventricular depolarization and repolarization in the cardiac cycle. Under normal circumstances, the QT interval is primarily determined by autonomic influences and varies inversely with heart rate. Several methods for calculation of the corrected QT interval on the basis of heart rate have been established in humans,3 and more recently, prediction intervals for QT intervals (corrected for heart rate) have been generated for healthy cats.2 A QT interval that exceeds the expected duration for a given heart rate may be a result of congenital long-QT syndrome or acquired forms of QT-interval prolongation. Congenital long-QT syndrome is caused by various gene mutations in cardiac ion channels,4 but to the authors' knowledge, it has not been described in animals other than transgenic mice used as a model of the syndrome.5 Acquired QT-interval prolongation can be caused by many factors in both humans and other animals, which include certain drugs, serum electrolyte abnormalities (eg, hypocalcemia, hypokalemia, and hypomagnesemia), intraventricular conduction delay, exercise, hypothermia, CNS disease, and bradyarrhythmias.4,6 Long-QT syndrome in humans is associated with a high predisposition for ventricular arrhythmias including ventricular tachycardia and torsades de pointes, which often results in ventricular fibrillation.4 In the cat of this report, serum electrolyte concentrations were within reference limits at the time of the QT-interval prolongation and there was no evidence of intraventricular conduction disturbance. Buprenorphine was administered to this cat and has the potential to block delayed rectifier potassium current in vitro at higher than clinically relevant concentrations, but buprenorphine-associated QT-interval prolongation has not been reported in vivo.7 Although propofol does not affect delayed rectifier potassium current or QT interval, sevoflurane inhibits this potassium current in a dose-dependent manner and significantly prolongs the QT interval in humans and other animals.8,9 Additionally, the cat was severely hypothermic and bradycardic and had clinical signs attributable to CNS disease (although no specific lesion could be identified).
Abnormalities of ventricular repolarization may be reflected in the T wave as a change in amplitude, shape, or polarity. T-wave alternans is a beat-to-beat alternation in the amplitude or polarity of the ST segment and T wave and may develop secondary to changes in the QRS complex, as is the case with electrical alternans. However, isolated T-wave alternans occurs independent of changes in ventricular depolarization,1,10 and this was evident in the ECG traces obtained from the cat of this report. There are several causes of T-wave abnormalities, but the causes of T-wave alternans are much more specific. In dogs and cats, this phenomenon has been associated with myocardial ischemia, increases in circulating concentrations of catecholamines, hypocalcemia, and acute increases in sympathetic discharge.1,6 In addition to these reported causes, T-wave alternans has been associated with long-QT syndrome in humans.10
Several experimental studies11,12 have investigated conditions under which it is possible to induce T-wave alternans in animals. In 1 study,11 hypocalcemia was induced in anesthetized dogs and T-wave alternans consistently developed at the time that the serum ionized calcium concentration was significantly reduced. T-wave alternans always developed after notable QTinterval prolongation and was always associated with mechanical alternans. Calcium infusion reversed the T-wave alternans, QT-interval prolongation, and mechanical alternans. In another study,12 anesthetized cats underwent vagotomy and T-wave alternans was induced by applying electrical stimulation to the stellate ganglia, which provide sympathetic innervation to the heart. Similarly, QT-interval prolongation and mechanical alternans always occurred with T-wave alternans, and these abnormalities all resolved shortly after the stimulus ended. The results of these experiments illustrate the ability of hypocalcemia and sympathetic stimulation to cause T-wave alternans and the association of T-wave alternans with a prolonged QT interval and mechanical alternans.
T-wave alternans reflects a spatial or temporal dispersion of ventricular repolarization.10 Spatial dispersion means that at a given time during the cardiac cycle, ventricular myocardial cells may be in different phases of repolarization, which may lead to regions of slowed conduction and the development of reentrant circuits. Temporal dispersion means that small beat-tobeat changes in the R-R interval may cause large changes in action potential duration, leading to wavefront fractionation and reentry. Alterations in action potential duration may be caused by alterations in cytosolic calcium concentration, and this may explain the presence of mechanical alternans with T-wave alternans. Both spatial and temporal dispersion of ventricular repolarization may lead to ventricular tachycardia or ventricular fibrillation.10 In humans, it is known that T-wave alternans represents electrical instability and may immediately precede ventricular tachyarrhythmias and sudden cardiac death, especially in patients with long-QT syndrome.13 Macrovolt T-wave alternans (grossly visible on a standard surface ECG) is a rare finding; however, the detection of microvolt T-wave alternans by use of sensitive computer algorithms is useful in human medicine for risk stratification of patients with conditions that may predispose them to sudden cardiac death.14
The cat of this report was not hypocalcemic and did not have evidence of increased circulating concentrations of catecholamines, but it did have hypertrophic cardiomyopathy, which may lead to myocardial ischemia. Acute changes in sympathetic stimulation may have also been caused by the suspected CNS disease or variation in the plane of anesthesia. Additionally, the bradycardia and prolonged QT-interval caused by hypothermia and, possibly, the administered anesthetic drugs could be predisposing factors for the development of T-wave alternans. Pulsus alternans resulting from mechanical alternans was not detected via digital palpation of the femoral pulses; however, no direct arterial pressure monitoring was available to detect small variations in systolic blood pressure. The cat did not develop any ventricular arrhythmias, and both the T-wave alternans and QT-interval prolongation resolved with rapid warming and recovery from anesthesia. Although QT-interval prolongation is an uncommon finding in veterinary patients and macrovolt T-wave alternans is an even more infrequent finding, recognition of both is important because they may be markers for development of ventricular arrhythmias and even sudden death. The combination of factors that prolong the QT interval and lead to T-wave alternans has the potential to be life threatening; therefore, all predisposing factors should be explored and corrected when these ECG findings are detected.
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