QT interval prolongation may occur as a congenital trait or be acquired; the prevalence of the inherited long QT syndrome is estimated to 1:2.500 whereas the frequency of acquired QT syndrome has not been reported in population-based studies [5
]. In this study, we show that QT interval prolongation is common in the cardiothoracic intensive care unit among unselected prospectively studied patients following cardiac surgery. In fact, 18% of patients displayed a QTc interval longer than 500 ms in the immediate postoperative period. Similar results have been published previously; in 18% of 900 patients admitted to dedicated cardiology beds the QT duration was >500 ms [6
]. In addition, it was shown that QT interval prolongation among medical patients was common (22% of 537 patients) and related to the use of QT interval prolonging drugs, hypokalemia and liver disease [7
]. Additional factors such as age, gender, congestive heart failure and bradycardia may contribute to prolong the QT duration [8
]. We document that the QT interval prolongation observed among patients having undergone cardiac surgery is acquired/enhanced in the postoperative period. Based on our data, the combined effects of the surgical trauma and the medications administered are associated with prolongation of the QT interval. However, we were not able to correlate the observed QT interval prolongation to cardiac or renal dysfunction or to increased mortality. Also, Pasquier et al. did not demonstrate increased risk of death among patients with QT interval prolongation [7
]. In contrast, others have documented that QT interval prolongation in consecutively monitored patients was associated with an increased risk of cardiac arrest and death [6
]. A study from the Stanford University including 537 acutely ill medical, surgical and trauma patients monitored by an automated QTc interval analysis software documented QTc interval prolongation in 24% of patients and linked the observed QT interval prolongation to in-hospital cardiac arrests [9
]. In a report by Letsas et al. 6 of 21 patients with a QTc interval longer than 500 ms developed malignant arrhythmias [3
]. Methodological variations may in part account for diverging conclusions; the 259 patients included in the Prolonqit study were included consecutively during the 6-month study period whereas the 21 patients studied by Letsas et al. were selected due to significant QT interval prolongation during a 33-month period. In addition, our small sample size may have obscured any clear signal that QT interval prolongation is associated with arrhythmic death following cardiothoracic surgery. In addition it is clear that any given drug’s effect on QT duration does not automatically translate to an increased risk of cardiac arrhythmias; amiodarone often produces significant QT interval prolongation but is rarely pro-arrhythmic, whereas a drug such as haloperidol exerts only a minor effect on QT duration but has a significant pro-arrhythmic potential. These differences may reflect additional effects of the individual drugs. For instance amiodarone affects a number of cardiac ion channels with presumed counteracting effects on its QT interval prolongating properties [8
]. Furthermore, the routine perioperative use of temporary cardiac pacemakers set at 80 beats per minute in our patients may have hindered the development of torsades de pointes in a number of patients as temporary pacing is in fact an empirical treatment option for suppression of ventricular tachyarrhythmias in patients with QT prolongation.
At present, physicians appreciate the existence of the syndrome of acquired or iatrogenic QT interval prolongation. The fact, that 2-3% of prescription drugs have the ability to prolong the QT interval, implies that we need to understand the consequences of this phenomenon [12
]. Currently, conclusions from clinical studies are conflicting as discussed above. In epidemiological studies estimating the risk of death in persons taking QT interval prolonging drugs, event rates are very low compared to the number of persons studied and a direct comparison of risk between different drugs is difficult to ascertain. However, one study did show that two specific antidepressants – citalopram and nortriptyline – were associated with an increased rate of cardiac arrest [13
], but this association may in part be due to the widespread use of these specific drugs in comparison to other drugs investigated for whom no increase in risk could be proved. It is also possible that malignant arrhythmias following pharmacologically induced QT interval prolongation require a particular susceptibility; approximately 50% of cardiac arrest survivors (in whom the cardiac arrest was considered to be due to acquired QT interval prolongation) developed recurrent malignant arrhythmias during a 10-year follow-up period despite no identifiable triggers at recurrence [14
]. A joint report from the Societies of Psychiatry and Cardiology in Denmark have suggested a stepwise approach when prescribing QT interval prolonging drugs to psychiatric patients; suggestions include screening for symptoms and risk factors for QT interval prolongation, avoidance of polypharmacy as well as repeated ECG screening which seems time-consuming and challenging to implement [15
]. We found that 63% of consecutively included patients undergoing cardiac surgery were administered QT interval prolonging drugs (or on average 1.4 drugs/patient) in the immediate postoperative period. The period of time during the postoperative phase where the QT interval is prolonged may determine the number of arrhythmic events. This susceptible period may be short for surgical patients generally recovering rapidly. In addition, the use of QT interval prolonging drugs is probably biased; the sickest patients will receive more medications when compared to uncomplicated patients and the underlying multitude of diseases battled as well as the medications prescribed may combine to affect cardiac repolarization. Furthermore, patients in whom QT interval prolongation is succeeded by malignant arrhythmias are apparently frailer than patients not displaying malignant arrhythmias when assessing the prevalence of for example reduced left ventricular function and renal dysfunction [3
]. As such, risk factors for QT interval prolongation were abundant among the few patients that did develop malignant tachyarrhythmias (data not shown), even though our data did not find a statistical association between the QT interval duration and arrhythmias and/or death.