QT interval: metric for cardiac prognosis?

The electrocardiogram (ECG) is a widely available and inexpensive, yet informative, screening tool for underlying heart disease. Myocardial infarction, left ventricular hypertrophy, and left bundle branch block are common causes of abnormal ventricular depolarization. Resultant alterations in the QRS complex either directly or indirectly reflect cardiac pathology that may have an adverse effect on survival. Aberrations of ventricular repolarization, which manifest as ST-T waveform abnormalities, also constitute a risk factor for cardiovascular death (1), because they can be a marker of ischemic heart disease, left ventricular hypertrophy, or cardiomyopathy. These disease processes may additionally affect the overall duration of ventricular repolarization, as approximated by the QT interval, which tends to be prolonged in these settings (2). However, as a prognostic tool, the QT interval generally has not received as much attention as the QRS complex and ST-T waveform. In the past two decades, greater awareness and understanding of the congenital long QT syndrome have sparked renewed interest in the QT interval as a window into myocyte electropathophysiology. Although a relatively rare condition, the congenital long QT syndrome has taught us about the various heritable (mainly potassium) ion channel disturbances that cause prolongation of the cardiac action potential and QT interval (3). Similar alterations in cardiac ion channel function and QT prolongation may occur on an acquired basis due to myocardial disease, electrolyte disturbances, or use of certain antiarrhythmic drugs (2– 4). Prolonged repolarization can set the stage for torsade de pointes, a polymorphic ventricular tachycardia that may lead to ventricular fibrillation and sudden cardiac death. Moreover, in the congenital long QT syndrome, the risk of cardiac events (syncope or sudden death, presumably caused by torsade de pointes) is related to the magnitude of the QT interval (5). Thus, a clinical and mechanistic paradigm linking the QT interval to the risk of sudden cardiac death has evolved. A number of population studies (6 –11) have been undertaken in recent years to investigate the possible relation between heart rate– corrected QT interval (QTc) and cardiovascular mortality (Table). Most (7–11) but not all (6) of these studies indeed show an increased relative risk (RR) (range, 1.2 to 4.3) of death due to cardiovascular or coronary heart disease in subjects with a QTc above a certain cutoff—traditionally of about 440 ms— compared with a reference group with a relatively short QTc. Yet, despite a general consistency in trend, the increased relative risks have not always been statistically significant (95% lower confidence limit beyond 1.00) for all outcomes, or for both sexes, within a given study. In the two studies that specifically looked at sudden death outcomes (6,11), the relative risk in the longer QTc groups (range, 1.31 to 1.50) was not significantly greater than 1.00. Furthermore, the Table shows that the QTc interval was not associated with an increased risk of death due to cardiovascular or coronary heart disease among the “Healthy Population Subset”, that is individuals without clinical or ECG evidence of structural heart disease. This may in part explain the negative results of the Framingham study (6), which excluded subjects with coronary heart disease at baseline. In the present issue of the Journal, Robbins et al (12) present relevant data from the Cardiovascular Health Study. The authors studied 4988 subjects (40.1% male; 14.7% African American), all aged 65 years, from four communities in the United States, after excluding subjects who had a QRS duration 120 ms or atrial fibrillation. The median follow-up was 10.5 years. Mortality was adjusted for risk factors for coronary artery disease and for exposure to QT-prolonging antiarrhythmic medications. In the longest QTc quintile ( 450 ms), the adjusted relative risk of mortality due to coronary heart disease was significantly greater than 1.00 for patients with (RR 2.0) as well as for those without (RR 1.6) known coronary heart disease. Although the former observation is compatible with most previous studies that included subjects with heart disease, the latter finding in a seemingly healthier subset (albeit with a borderline lower 95% confidence limit of 1.01 for RR) is at variance with prior observations. An innately higher baseline risk in the elderly individuals studied by the authors might account for this discrepancy. Of note, when further adjustment was made for left ventricular hypertrophy by ECG criteria, the relative risk of mortality due to coronary heart disease in subjects with a QTc interval 450 ms was no longer significantly greater than 1.00 in those with (RR 1.41) or without (RR 1.50) known coronary heart disAm J Med. 2003;115:732–734. From the Department of Internal Medicine (MHL, FM), Division of Cardiovascular Medicine, University of Michigan; and the Michigan Center for Genomics and Public Health (MHL), Ann Arbor, Michigan. Requests for reprints should be addressed to Michael H. Lehmann, MD, Women’s Hospital, L3119, Box 0273, 1500 East Medical Center Drive, Ann Arbor, Michigan 48109-0273, or lehmann@umich.edu.