Length of the QT interval: determinants and prognostic implications in a population-based prospective study of older men☆
Introduction
The QT interval corrected for heart rate (QTc) measures the time from the start of ventricular depolarization to the completion of repolarization. In the clinical context, longer QTc intervals are implicated in the generation of ventricular arrhythmias such as torsades de pointes, which can degenerate to fatal ventricular fibrillation. Long QT syndrome has been conceptualized as 2 groups: inherited and acquired. Our understanding of the inherited type has developed considerably, but relatively less is known about acquired QTc lengthening.1 A number of population-based cohort studies have investigated the prognostic importance of long QTc in adults with varying results.2, 3, 4, 5, 6, 7, 8 Many have shown a tendency toward increased mortality with longer QTc intervals, particularly above a cutoff value of 440 milliseconds.2, 6, 7, 9 It is likely that in an older population, much of this QTc lengthening is acquired, but little is known about the determinants of QTc in the general population.
There are many factors that may lengthen the QTc. Biochemical abnormalities including hypokalemia, hypomagnesemia, and hypocalcemia are implicated.10 Although there are large studies to show hypokalemia might lengthen the QTc,11, 12 there is much less information on hypomagnesemia and hypocalcemia. Drugs, including some antiarrhythmic medications and noncardiac drugs ranging from psychiatric medications to certain antibiotics, may lengthen the QTc interval.13 Intracranial injury has been implicated in QTc lengthening, and there has been some interest in the development of long QTc in people with liver cirrhosis and patient's with end-stage renal disease.14, 11, 15
There is little evidence on the importance of such determinants of the QTc in the general population and how they affect its prognostic value. We have therefore explored the determinants of lengthening QTc interval at the population level in a cohort of older men. Potential determinants examined include a range of biochemical factors, medications, as well as established cardiovascular risk factors including diabetes, cigarette smoking, and hypertension. Phenomena that lengthen the QRS complex inevitably lead to a longer QTc, so to look at the effect of QTc purely, these have been excluded. We have also examined the prognostic value of QTc interval and used multivariable survival analyses to adjust for these determinants to ascertain if the QTc interval is an independent predictor of prognosis.
Section snippets
Study population
The British Regional Heart Study is a prospective cohort study investigating cardiovascular risk. Between 1978 and 1980, 7735 men aged 40 to 59 years were selected from 24 medium-sized British towns using age-sex registers from one general practice in each town. Between 1998 and 2000, all the surviving men were recalled for a 20-year reexamination, and 4252 men attended (77% response rate). The examination included physical measurements, resting 12-lead electrocardiograms (ECGs) and blood
Results
Follow-up data were available on the entire cohort. Corrected QT interval data were available for 4231 of the 4252 men, of whom 295 were excluded for having abnormalities prolonging the QRS interval, as defined in the methods. A further 361 participants did not have complete biochemical data, leaving complete data for analysis on 3596 participants. All the variables in Table 1, Table 2 were used as adjustors in the multivariable regression and multivariable proportional hazards regression. The
Discussion
This study shows that a long QTc is an independent prognostic indicator of all-cause mortality and establishes determinants of the QTc at a population level. It suggests previously undocumented associations, particularly with serum urate concentrations, and casts doubt on others such as with hypomagnesaemia.
When ECGs were performed on this cohort at the beginning of this study 20 years before the data analyzed here, less than 1% of the cohort had a long QTc.25 This suggests that most of the QTc
Acknowledgments
Biochemical analyses were carried out in the Department of Chemical Pathology, Royal Free Hospital (Dr M. Thomas).
References (34)
- et al.
Heart rate-corrected QT interval prolongation predicts risk of coronary heart disease in black and white middle-aged men and women: the ARIC study
J Am Coll Cardiol
(2004) Clinical and therapeutic aspects of congenital and acquired long QT syndrome
Am J Med
(2002)- et al.
Electrocardiographic abnormalities and uremic cardiomyopathy
Kidney Int
(2005) - et al.
A comparison of commonly used QT correction formulae: the effect of heart rate on the QTc of normal ECGs
J Electrocardiol
(2004) - et al.
Bazett and Fridericia QT correction formulas interfere with measurement of drug-induced changes in QT interval
Heart Rhythm
(2006) - et al.
The association between the length of the QT interval and mortality in the Cardiovascular Health Study
Am J Med
(2003) - et al.
Duration of the QT interval and total and cardiovascular mortality in healthy persons (The Framingham Heart Study experience)
Am J Cardiol
(1991) - et al.
Prolonged QTc interval and risk of sudden cardiac death in a population of older adults
J Am Coll Cardiol
(2006) - et al.
Genetics of acquired long QT syndrome
J Clin Invest
(2005) - et al.
Prolonged QT interval predicts cardiac and all-cause mortality in the elderly. The Rotterdam Study
Eur Heart J
(1999)
QT interval as a cardiac risk factor in a middle aged population
Heart
Assessment of QT interval and QT dispersion for prediction of all-cause and cardiovascular mortality in American Indians: the Strong Heart Study
Circulation
The prognostic value of the QT interval and QT interval dispersion in all-cause and cardiac mortality and morbidity in a population of Danish citizens
Eur Heart J
QT interval prolongation predicts cardiovascular mortality in an apparently healthy population
Circulation
Association between QT interval and coronary heart disease in middle-aged and elderly men. The Zutphen Study
Circulation
QTc prolongation measured by standard 12-lead electrocardiography is an independent risk factor for sudden death due to cardiac arrest
Circulation
Long QT syndrome: reduced repolarization reserve and the genetic link
J Intern Med
Cited by (47)
The Impact of Chronic Disease on the Corrected QT (QTc) Value in Women in a British Columbia First Nations Population
2024, Canadian Journal of CardiologyA QTc risk score in patients with obstructive sleep apnea
2023, Sleep MedicineRelationship between a risk score for QT interval prolongation and mortality across rural and urban inpatient facilities
2023, Journal of ElectrocardiologyCitation Excerpt :Haugaa et al. demonstrated even higher mortality rate of almost 4-fold higher in patients with QTc ≥ 500 ms compared to those with QT c < 500 ms. [17] There is also extensive evidence that suggests the link between prolonged QTc and life-threatening TdP, cardiac arrest, cardiovascular death and all-cause mortality. [1,22–32] Overall, many of risk factors in the Tisdale risk score have demonstrated an association with mortality. [1,8,20–32] Our findings were also aligned with the previous literature showing that almost all of the Tisdale risk factors were associated with increased risk of mortality, except female sex and serum K+ ≤ 3.5 mEq.
Prolongation of the heart rate-corrected QT interval is associated with cardiovascular diseases: Systematic review and meta-analysis
2023, Archives of Cardiovascular DiseasesTraditional risk factors for QT interval prolongation and torsades de pointes
2022, Torsades de PointesLong QT Syndrome and Perioperative Torsades de Pointes: What the Anesthesiologist Should Know
2022, Journal of Cardiothoracic and Vascular AnesthesiaCitation Excerpt :Acquired long QT syndrome (aLQTS) is characterized by QT prolongation that is secondary to exogenous stressors such as drug administration, electrolyte disturbances (eg, hypokalemia, hypomagnesemia, hypochloremia, and hyponatremia), hypothermia, cardiac disease (eg, hypertension, congestive heart failure, ischemic cardiomyopathy, left ventricular hypertrophy, and after cardiopulmonary bypass after cardiac surgery52-54), cerebrovascular injury, renal failure, cirrhosis, and endocrine dysfunction (eg, diabetes mellitus, thyroid disease, testosterone deficiency). Advancing age, female sex, and elevated body mass index are known risk factors for aLQTS.55,56 Drug-induced long QT syndrome (diLQTS) often is regarded as the most common type of aLQTS; however, its incidence is challenging to estimate given that patients at risk for diLQTS often have multiple other nondrug risk factors.
- ☆
The British Regional Heart Study is supported by the British Heart Foundation and receives support from the Department of Health. S.M.A. Sohaib was funded through the North Central Thames Foundation School Academic Foundation Programme at University College London.