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The perils of QT prolongation under scrutiny

A computer clinical decision support system (CDSS) incorporating a validated risk score for QTc prolongation influences the prescribing of QT-prolonging drugs and reduces the risk of QTc interval prolongation in hospitalised patients with torsades de pointes risk factors, according to a study published recently in Circulation: Cardiovascular Quality and Outcomes.1

The authors evaluated 2,400 patients admitted to cardiac care units at an urban academic medical center. A CDSS incorporating a validated risk score for QTc prolongation was developed and implemented using information extracted from patients’ electronic medical records. When a drug associated with torsades de pointes was prescribed to a patient at moderate or high risk for QTc interval prolongation, a computer alert appeared on the screen to the pharmacist entering the order, who could then consult the prescriber on alternative therapies and implement more intensive monitoring. QTc interval prolongation was defined as QTc interval >500 ms or increase in QTc of ≥60 ms from baseline; for patients who presented with QTc >500 ms, QTc prolongation was defined solely as increase in QTc ≥60 ms from baseline.

End points were assessed before (n=1,200) and after (n=1,200) implementation of the CDSS. CDSS implementation was independently associated with a reduced risk of QTc prolongation (adjusted odds ratio, 0.65; 95% confidence interval, 0.56–0.89; P<0.0001). Furthermore, CDSS implementation reduced the prescribing of noncardiac medications known to cause torsades de pointes, including fluoroquinolones and intravenous haloperidol (adjusted odds ratio, 0.79; 95% confidence interval, 0.63–0.91; P=0.03).

Arrhythmia risk induced by psychotropic medications

The increased risk of malignant arrhythmia associated with treatment with psychotropic drugs calls for new clinical guidelines, according to a review of data from various authorities, published recently in the European Heart Journal.2

The authors observe that several drugs used in the treatment of mental diseases are associated with an increased risk of sudden cardiac death (SCD). Numerous case reports of drug-induced malignant arrhythmia and epidemiological studies, associating the use of specific drugs with SCD, strongly support the presence of an increased risk, they say.

Whereas the absolute risk of drug-induced life-threatening arrhythmia may be relatively low, even small increments in risk of SCD may have a major health impact considering that millions of patients are treated with psychotropics, the review continues. In subgroups of pre-disposed patients – e.g. patients with cardiac diseases or other co-morbidities, the elderly or patients treated with other negatively interacting drugs – the absolute risk of drug-induced arrhythmia may be considerable.

On the other hand, several of the major mental disorders are associated with a large risk of suicide if untreated, say the authors. The observed risk of malignant arrhythmia associated with treatment with psychotropic drugs calls for clinical guidelines integrating the risk of the individual drug and other potentially interacting risk factors. In this review, data from various authorities on the risk of arrhythmia associated with psychotropic medications are weighted and categorised into three risk categories.

Additionally, the authors suggest a clinically applicable algorithm to reduce the risk of malignant arrhythmia in patients to be treated with psychotropic medications. The algorithm integrates the risk categories of the individual drugs and pre-disposing risk factors and suggests a follow-up for patients with an increased risk. The authors believe this clinically manageable guideline might improve safety in the many and rapidly increasing number of patients on psychotropic drugs.

Risk prediction of cardiovascular death based on the QTc interval

The accuracy of a personalised cardiovascular death (CVD) prognosis can be improved when the QTc interval is introduced to a conventional risk model for CVD, according to a study published recently in the European Heart Journal.3

Using a large, contemporary primary care population the authors aimed to provide absolute long-term risks of CVD based on the QTc interval and to test whether the QTc interval is of value in risk prediction of CVD on an individual level.

Digital electrocardiograms from 173,529 primary care patients aged 50–90 years were collected during 2001–11. The Framingham formula was used for heart rate-correction of the QT interval. Data on medication, comorbidity, and outcomes were retrieved from administrative registries. During a median follow-up period of 6.1 years, 6,647 persons died from cardiovascular causes.

Long-term risks of CVD were estimated for subgroups defined by age, gender, cardiovascular disease, and QTc interval categories. In general, the authors observed an increased risk of CVD for both very short and long QTc intervals. Prolongation of the QTc interval resulted in the worst prognosis for men whereas in women, a very short QTc interval was equivalent in risk to a borderline prolonged QTc interval.

The effect of the QTc interval on the absolute risk of CVD was most pronounced in the elderly and in those with cardiovascular disease whereas the effect was negligible for middle-aged women without cardiovascular disease. The most important improvement in prediction accuracy was noted for women aged 70–90 years. In this subgroup, a total of 9.5% were reclassified (7.2% more accurately vs. 2.3% more inaccurately) within clinically relevant 5-year risk groups when the QTc interval was added to a conventional risk model for CVD.


1. Tisdale JE, Jaynes HA, Kingery JR, Overholser BR, Mourad NA, Trujillo TN, Kovacs RJ. Effectiveness of a clinical decision support system for reducing the risk of QT interval prolongation in hospitalized patients. Circ Cardiovasc Qual Outcomes 2014;7:381–90.​CIRCOUTCOMES.113.000651

2. Fanoe S, Kristensen D, Fink-Jensen A, et al. Risk of arrhythmia induced by psychotropic medications: a proposal for clinical management. Eur Heart J 2014.

3. Nielsen JB, Graff C, Rasmussen PV, et al. Risk prediction of cardiovascular death based on the QTc interval: evaluating age and gender differences in a large primary care population. Eur Heart J 2014;35:1335–44.

Published on: May 28, 2014

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