Vector Quantization of T Wave Abnormalities Associated with a Predisposition to Ventricular Arrhythmias and Sudden Death

Abstract

Background: Previous studies have suggested that irregular T wave morphologies are associated with an increased risk of sudden death. However, automated characterization of T wave abnormalities has been hampered by the lack of suitable analysis techniques. In this study, we tested a new method of T wave analysis in German shepherd dogs with inherited ventricular arrhythmias and sudden death. Methods: Sets of 24-hour ambulatory ECG recordings obtained from unaffected (n = 6) and affected (n = 5) dogs were digitized, automatically annotated to label each R wave, and placed into a matrix with the R waves aligned. A vector quantization algorithm separated the QRS-T complexes into classes according to T wave morphology. The existence of notched T waves was determined by assessing the number of zero crossings of the first derivative during the T wave. Results: The duration of the QT interval was similar in affected and unaffected dogs (182 ? 14 ms vs 176 5 16 ms, respectively). However, T wave morphology differed between the two groups. Specifically, affected dogs had a higher percentage of notched T waves than unaffected dogs (41.6% 5 10.8% vs 5.0% -t 1.2%, respectively). Notched T waves did not appear at all times of day, nor were they present in all leads. Conclusion: Vector quantization and first derivative analyses were feasible and effective methods for detecting T wave abnormalities associated with the development of ventricular arrhythmias. These methods ultimately may be useful for risk stratification of patients susceptible to ventricular T wave; vector quantization; cardiac arrhythmias; sudden death arrhythmias and sudden death.

Heterogeneous Ventricular Repolarization Provides a Substrate for Arrhythmias in a German Shepherd Model of Spontaneous Arrhythmic Death

“…4,9 Such heterogeneity of repolarization can provide a substrate for reentry and pause-dependent ventricular tachycardia and might account for the abnormal T-wave morphology in afflicted dogs. 10,12 Our voltage-clamp data pinpoint the ionic basis of this heterogeneity. In afflicted animals, I Ks was significantly larger and I Kr significantly smaller anterobasally than anteroseptally whereas no differences in these currents occurred across the 2 LV regions in unafflicted dogs.…”

“…7,8 However, the substrate contributing to maintenance of this ventricular tachycardia remains unknown. The pause dependence of the arrhythmias as well as the observations that in afflicted dogs (1) the QT interval is not prolonged, 9,10 (2) LV sympathetic innervation is inhomogeneous, 11 and (3) frequent T-wave notching occurs, 10,12 raise the possibility that inhomogeneity of LV repolarization may constitute part of the arrhythmogenic substrate. Therefore, we studied action potential duration (APD) and isoproterenol responsiveness in multicellular sections from anterobasal, anteroseptal, and posterobasal LV midmyocardium, as well as epicardium and subendocardium of hearts from afflicted and unafflicted dogs.…”

Structural and Functional Basis for the Long QT Syndrome: Relevance to Veterinary Patients

“…129 The majority of industrial drug safety/toxicology laboratories use conscious dogs for preclinical in vivo ECG assessment 129 ; however, there is no standardized practice for investigation of drug-induced QT interval prolongation and little consensus regarding the optimal analysis of ECG data obtained from dogs. [129][130][131][132] In addition, preclinical evaluation of new agents is complicated by marked species differences in response to ion channel-blocking drugs, particularly I Kr blockers. 106 The major issues that remain unresolved in preclinical drug testing and development are identical to those that confront veterinary cardiologists, including the adequacy of different methods of ECG analysis, the prognostic significance of changes in the QT interval with respect to the development of ventricular arrhythmias, and the applicability of different methods of analysis and interpretation across and within species.…”

“…[134][135][136] More generally, repolarization abnormalities may not necessarily be reflected by alterations of the QT interval. 131,137,138 In these cases, other techniques, such as assessments of Twave dispersion or morphology, may be required. 131,139 However, the clinical utility of these and other advanced techniques for assessment of cardiac repolarization is unproven in veterinary patients.…”

“…131,137,138 In these cases, other techniques, such as assessments of Twave dispersion or morphology, may be required. 131,139 However, the clinical utility of these and other advanced techniques for assessment of cardiac repolarization is unproven in veterinary patients. 139,140 Even if unequivocal evidence for QT prolongation is present, the significance of this finding with respect to the development of ventricular arrhythmias may be uncertain.…”