QT dispersion (QTD), the difference between the maximum and minimum QT interval on the 12-lead electrocardiogram (ECG), is a marker of heterogeneity of ventricular repolarization.1 Previous studies have shown increased QTD to be a predictor of adverse outcomes in various cardiac disease states. Increased QTD has been found to be associated with cardiac arrhythmias and sudden cardiac death in patients with myocardial infarction, left ventricular hypertrophy, congestive heart failure, coronary artery disease, diabetes and end-stage renal disease.2–10 Acute brain injury has been shown to result in altered autonomic regulation of the cardiovascular system.1–13 Whether QTD measurement is influenced by acute brain injury remains unknown. Accordingly, the objective of this study was to determine the clinical significance of QTD measurement in patients hospitalized with acute cerebrovascular accidents (CVA) and transient ischemic attacks (TIA). Methods We retrospectively studied 140 consecutive patients (age, 72 ± 13 years) who were admitted to Winthrop University Hospital with acute neurological events between January 1, 1998 and April 30, 1998. Neurological events were defined as neurological symptoms, such as visual or speech disturbances, paresis or paralysis, loss of sensation, gait or equilibrium disturbance. The patients were excluded from the study in the case of altered mental status caused by metabolic disturbances, seizures or presence of brain masses. Neurological evaluation. A complete neurological evaluation was performed on all patients by an experienced neurologist. Three separate functional scales were used to re-evaluate patients on discharge: the National Institute of Health Stroke Scale (NIHSS), the Barthel Index and the Modified Rankin Scale.14–16 Clinical data were collected continuously during and after hospitalization and entered into the stroke database using standard definitions for each variable. The following clinical and demographic variables were analyzed: age, gender, diabetes, hypertension, hypercholesterolemia, current smoking, prior CVA or TIA, history of congestive heart failure, history of coronary disease, recent cardiac surgery (within 1 month), and carotid disease (defined as >= 40% stenosis in one or both carotid arteries by carotid Doppler imaging). The primary clinical endpoints analyzed in the study were mortality during hospitalization and the degree of neurological impairment determined by the NIHSS, Barthel Index and Modified Rankin scales upon discharge. Electrocardiographic data. The ECG data were retrospectively collected. The QTD measurements were calculated from the admission ECG, which was routinely obtained with a three-channel Burdick E310 electrocardiograph (Burdick Corporation, Milton, Wisconsin). The ECG tracings were recorded during quiet respiration at a paper speed of 25 mm/second and a manual calibration of 1 mV equal to 10 mm. The first ECGs available on presentation were analyzed manually by observers blinded to clinical data. The QT interval was measured to the nearest 10 msec in each of the presenting ECGs from the onset of the QRS complex to the end of the T-wave. In the presence of a U-wave, the end of the T-wave was determined using the tangent method on the descending limb of the T-wave and determined at which point it intersected the baseline.1 QTD was calculated as the difference between the maximum and minimal QT intervals. Heart rate and maximum QRS duration were also recorded. Interobserver and intraobserver variability of QTD measurements were evaluated in 10 randomly selected patients. For interobserver comparisons, a second investigator was blinded to the results of the first investigator. For intraobserver variability, an investigator was blinded to the measurements of his first analysis. Interobserver and intraobserver variability were expressed as the mean absolute difference between observations. Statistics. Data are expressed as means ± standard deviations. Univariate analyses were performed in categorical data using the Spearman correlation and the rank-sum and Kruskal-Wallis tests. Multivariate analyses were performed with the use of stepwise and forced multiple logistic regressions in order to determine independent correlates of hospital mortality. The presence of carotid disease was considered a categorical variable for multivariate analysis. Statistical significance was defined as a p-value Study limitations. This study is subject to the inherent limitations of a retrospective study. Six deaths occurred in patients with uninterpretable ECGs, leaving relatively few mortality events in patients with interpretable ECGs. All patients with TIA survived. Although QTD was not corrected for heart rate and QRS duration,29 there were no differences in these parameters between survivors and non-survivors. Although laterality was found to be predictive of stroke-related arrhythmias,13,30 presenting symptoms and infarct location on computed tomographic and magnetic resonance imaging studies were not considered. Medication effects cannot be completely excluded, as angiotensin-converting inhibitors, angiotensin receptor blockers and beta-blockers have been shown to reduce QTD in certain patient subgroups.31–34 QTD was not compared with other measures of autonomic regulation, but no gold standard remains for the interpretation of cardiovascular autonomic dysfunction in patients with cardiac disease or stroke.35 Moreover, the weak association between functional outcomes and QTD values preclude its routine use in predicting functional outcomes. Whether correction for heart rate would improve the predictive value of QTD remains unknown. Despite these limitations, we conclude that in patients presenting with acute neurological events, increased QTD on admission ECG was significantly related to hospital mortality and to functional outcomes on hospital discharge. Furthermore, increased QTD was related to the type of neurological event as QTD values were greater in patients with subarachnoid hemorrhages as compared to those with CVA and TIA. In this patient population, increasing QTS was also associated with advancing age, congestive heart failure and carotid disease, but not with atrial fibrillation, coronary disease or recent bypass surgery. Therefore, QTD would appear to reflect not only underlying heart disease but also acute neurological injury. The study population provides an accurate demographic representation of patients with acute neurological events encountered in clinical practice. It appears that both structural heart disease as well as altered cardiac neuroregulation can increase heterogeneity of ventricular repolarization. Further studies are needed for prospective validation and to determine the specific mechanisms by which QTD is influenced by acute neurologic events. Whether QTD is influenced by the presence of carotid disease independent of CVA or TIA remains unknown. In addition, serial changes in QTD and the long-term prognostic value of QTD in this setting merit further study.
1. Volka ME, Steinburg JS. Qt dispersion: Current and future clinical role. J Invas Cardiol 1996;8:363‚Äì369. 2. Buja G, Miorelli M, Turrini P, et al. Comparison of QT dispersion in hypertrophic cardiomyopathy between patients with and without ventricular arrhythmias and sudden death. Am J Cardiol 1993;72:973‚Äì976. 3. Barr CS, Naas A, Freeman M, et al. QT dispersion and sudden expected death in chronic heart failure. Lancet 1994;343:327‚Äì329. 4. Perkoioaki JS, Koistinen MJ, Yli-Mayry S, Huikuri HV. Dispersion of QT interval in patients with and without susceptibility to ventricular tachyarrhythmias after previous myocardial infarction. J Am Coll Cardiol 1995;26;174‚Äì179. 5. Zareba W, Moss AJ, Ie Cessie S. Dispersion of ventricular repolarization and arrhythmic death in coronary artery disease. Am J Cardiol 1994;74:550‚Äì553. 6. Higham PD, Furniss SS, Campbell RW. QT dispersion and components of the QT interval in ischemia and infarction. Br Heart J 1995;73:32‚Äì26. 7. Anastasiou-Nana MI, Nanas JN, Karagounis LA, et al. Relation of dispersion of QRS and QT in patients with advanced congestive heart failure to cardiac and sudden death mortality. Am J Cardiol 2000;85:1212‚Äì1217. 8. Kirvela M, Yli-Hankala A, Lindgren L. QT dispersion and autonomic function in diabetic and non-diabetic patients with renal failure. Br J Anaesth 1994;73:801‚Äì804. 9. Wei K, Dorian P, Newman D, Langer A. Association between QT dispersion and autonomic dysfunction in patients with diabetes mellitus. J Am Coll Cardiol 1995;6:859‚Äì863. 10. Veglio M, Chinaglia A, Cavallo P. The clinical utility of QT interval assessment in diabetes. Diabetes Nutr Metab 2000;13:356‚Äì365. 11. Hachinski VC. The clinical problem of brain and heart. Stroke 1993;24(Suppl 12):I10‚ÄìI12. 12. Oppenheimer SM. Neurogenic cardiac effects of cerebrovascular disease. Curr Opin Neurol 1994;7:20‚Äì24. 13. Tokgozoglu SL, Batur MK, Topcuoglu MA, et al. Effects of stroke localization on cardiac autonomic balance and sudden death. Stroke 1999;30:1307‚Äì1311. 14. Brott T, Adams HP Jr., Olinger CP, et al. Measurements of acute cerebral infarction: A clinical examination scale. Stroke 1989;20:864‚Äì870. 15. Mahoney FD, Barthel DW. Functional evaluation: The Barthel index. Md State Med J 1965;14:61‚Äì63. 16. Rankin J. Cerebral vascular accidents in patients over the age of 60. Scott Med J 1957;2:200‚Äì215. 17. Ziegler D, Weise F, Langen KJ, et al. Effect of glycemic control on myocardial innervation assessed by (123I) metaiodobenzylguanidine scintigraphy: A 4-year prospective study in IDDM patients. Diabetologia 1998;41:443‚Äì451. 18. Goldstein D. The electrocardiogram in stroke: Relationship to pathophysiological type and comparison with prior tracings. Stroke 1979;10:253‚Äì259. 19. Korpelanian JT, Sotaniemi KA, Huikuri HV, Myllyla VV. Abnormal heart rate variability as a manifestation of autonomic dysfunction in hemispheric brain infarction. Stroke 1996;27:2059‚Äì2063. 20. Korpelanian JT, Sotaniemi KA, Huikuri HV, Myllyla VV. Circadian rhythm of heart rate variability is reversibly abolished in ischemic stroke. Stroke 1997;28:2150‚Äì2154. 21. Robinson TG, James M, Youde J, et al. Cardiac baroreceptor is impaired after acute stroke. Stroke 1997;28:1671‚Äì1676. 22. Randall T, Tanskanen P, Scheinin M, et al. QT dispersion after subarachnoid hemorrhage. J Neurosurg Anesthesiol 1999;11:163‚Äì166. 23. Yoshida N, Nozawa T, Igawa A, et al. Modulation of ventricular repolarization and R-R interval is altered in patients with globally impaired cardiac 123I-MIBG uptake. Ann Noninvasive Electrocardiol 2001;6:55‚Äì63. 24. Shimizu M, Ino H, Okeie K, et al. Increased QT dispersion does not reflect the increased regional variation of cardiac sympathetic nervous activity in hypertrophic cardiomyopathy. Am Heart J 2001;142:358‚Äì362. 25. Nakagawa M, Takahashi N, Iwao T, et al. Evaluation of autonomic influences on QT dispersion using the head-up tilt test in healthy subjects. Pacing Clin Electrophysiol 1999;22:1158‚Äì1163. 26. Creager MA, Creager SJ. Arterial baroreflex regulation of blood pressure in patients with congestive heart failure. J Am Coll Cardiol 1994;23:401‚Äì405. 27. Akinola A, Mathias CJ, Mansfield A, et al. Cardiovascular, autonomic, and plasma catecholamines responses in unilateral and bilateral carotid artery stenosis. J Neurol Neurosurg Psychiatry 1999;67:428‚Äì432. 28. Perkiomaki J, Sourander L, Levomaki L, et al. QT dispersion and mortality in the elderly. Ann Noninvasive Electrocardiol 2001;6:183‚Äì192. 29. Kautzer J, Yi G, Camm AJ, Malik M. Short- and long-term reproducibility of QT, QTc, and QT dispersion measurements in healthy subjects. PACE 1994;17:928‚Äì937. 30. Lane RD, Wallace JD, Petrosky PP, et al. Supraventricular tachycardia in patients with right hemisphere strokes. Stroke 1992;23:362‚Äì366. 31. Ranade V, Molnar J, Khokher T, et al. Effect of angiotensin-converting enzyme therapy on QT interval dispersion. Am J Ther 1999;6:257‚Äì261. 32. Brooksby P, Robinson PJ, Segal R, et al. Effects of losartin and captopril on QT dispersion in elderly patients with heart failure. The ELITE Study Group. Lancet 1999;354:395‚Äì396. 33. Yee KM, Pringle SD, Struthers AD. Circadian variation in the effects of aldosterone blockade on heart rate variability and QT dispersion in congestive heart failure. J Am Coll Cardiol 2001;37:1800‚Äì1807. 34. Fesmire SI, Marcoux LG, Lyyski DS, et al. Effect of selective versus nonselective beta blockade on QT dispersion in patients with nonischemic dilated cardiomyopathy. Am J Cardiol 1999;84:350‚Äì354. 35. Sleight P. The importance of autonomic nervous system in health and disease. Aust N Z Med 1997;27:467‚Äì473.