CORRESPONDENCE: LETTER TO THE EDITOR
Prolonged QTc Interval and Sudden Cardiac Death in Older Adults
Michael H. Lehmann, MD*
* Women’s Hospital, L3119, Box 0273, University of Michigan Medical Center, 1500 East Medical Center Drive, Ann Arbor, Michigan 48109-0273 (Email: lehmann{at}umich.edu).
With considerable interest I read the recent study by Straus et al. (1) reporting QTc prolongation (>450 ms in men, and >470 ms in women) as an independent predictor of sudden cardiac death (SCD) in the large population-based Rotterdam study cohort of older adults (aged  55 years). Although various clinical and epidemiologic risk factors—including hypertension, myocardial infarction, heart failure, and diabetes—were incorporated into their multivariable model for calculating hazard ratios, the investigators did not include several important electrocardiographic (ECG) parameters that may be informative regarding susceptibility to SCD, QT prolongation, or both.
Chief among these are QRS voltage and ST-T criteria for left ventricular hypertrophy (LVH). Even after statistically adjusting for hypertension, LVH is a known risk factor for cardiac mortality, and specifically SCD (2,3); LVH also causes electrophysiologic remodeling that results in prolongation of action potential duration and the QT interval (4). These alterations, together with concomitant conduction delays—which, macroscopically, may manifest with various degrees of QRS prolongation (relative or absolute)—set the stage for ventricular tachyarrhythmogenesis and SCD. An ST-T "strain" pattern in the setting of ECG–LVH confers increased risk of heart failure (5), which in turn may predispose to SCD, in part through prolonged repolarization (6). Of course, ST-segment depression and "nonspecific" or "minor" ST-T abnormalities may also be indications of subclinical coronary atherosclerosis (7,8), another risk factor for SCD.
A previous study of the Rotterdam cohort by Kors et al. (9) demonstrated that an abnormal T-wave axis (i.e., falling between either –15° and –180°, or +105° and +180°) was a statistically significant predictor of SCD (hazard ratio 3.1 [95% confidence interval, 1.7 to 5.5], after adjustment for age, gender, and cardiovascular risk factors). Moreover, using a statistical model in which prolonged QTc, abnormal T axis, and other relevant ECG abnormalities (as previously noted) were entered simultaneously, Kors et al. (9) found that abnormal T axis—but not prolonged QTc—was an independent predictor of cardiac death (44% of which cases were sudden).
Also omitted from the statistical analysis of Straus et al. (1) were 2 predictors of prolonged rate-corrected QT (10), namely QRS duration (which can be relatively longer [not necessarily 120 ms] in settings of LVH or myocardial fibrosis) and use of class IA antiarrhythmic drug (in vogue during the Rotterdam study period).
Given the potential mechanistic, epidemiologic, and clinical implications of the investigators’ study, until their multivariable model is expanded to include the established (and biologically plausible) covariates discussed above, it is probably premature to conclude that prolonged QTc is a statistically independent predictor of SCD in older adults.
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1. Straus SMJM, Kors JA, de Bruin ML, et al. Prolonged QTc-interval and risk of sudden cardiac death in a population of older adults J Am Coll Cardiol 2006;47:362-367.[Abstract/Free Full Text]2. Kannel WB, Dannen AL, Levy D. Population implications of electrocardiographic left ventricular hypertrophy Am J Cardiol 1987;60:85I-93I.[Medline] 3. Haider AW, Larson MG, Benjamin EJ, Levy D. Increased left ventricular mass and hypertrophy are associated with increased risk for sudden death J Am Coll Cardiol 1998;32:1454-1459.[Abstract/Free Full Text] 4. Swynghedauw B, Baillard C, Milliez P. The long QT interval is not only inherited but is also linked to cardiac hypertrophy J Mol Med 2003;81:336-345.[Web of Science][Medline] 5. Okin PM, Devereux RB, Nieminen MS, et al. LIFE Study Investigators Electrocardiographic strain pattern and prediction of new-onset congestive heart failure in hypertensive patients: the Losartan Intervention for Endpoint Reduction in Hypertension (LIFE) study Circulation 2006;113:67-73.[Abstract/Free Full Text] 6. Tomaselli GF, Beuckelmann DJ, Calkins HG, et al. Sudden cardiac death in heart failure: the role of abnormal repolarization Circulation 1994;90:2534-2539.[Abstract/Free Full Text] 7. Liao Y, Liu K, Dyer A, et al. Major and minor electrocardiographic abnormalities and risk of death from coronary heart disease, cardiovascular diseases and all causes in men and women J Am Coll Cardiol 1988;12:1494-1500.[Abstract] 8. Sigurdsson E, Sigfusson N, Sigvaldason H, Gudmundur T. Silent ST-T changes in an epidemiologic cohort study—a marker of hypertension or coronary heart disease, or both: the Reykjavik study J Am Coll Cardiol 1996;27:1140-1147.[Abstract] 9. Kors JA, de Bruyne MC, Hoes AW, et al. T axis as an indicator of risk of cardiac events in elderly people Lancet 1998;352:601-605.[CrossRef][Web of Science][Medline] 10. Rautaharju PM, Manolio TA, Psaty BM, Borhani NO, Furberg CD, Cardiovascular Health Study Research Group Correlates of QT prolongation in older adults (the Cardiovascular Health Study) Am J Cardiol 1994;73:999-1002.[CrossRef][Web of Science][Medline]
Related Article
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Reply
- Sabine M.J.M. Straus, Jan A. Kors, and Bruno H.Ch. Stricker
J. Am. Coll. Cardiol. 2006 48: 1474.
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