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By Chris Kaiser, Cardiology Editor, MedPage Today
Published: April 30, 2013
Reviewed by F. Perry Wilson, MD, MSCE; Instructor of Medicine, Perelman School of Medicine at the University of Pennsylvania
- Note that this single-center study demonstrated that prolonged QT intervals on ECGs were associated with all-cause mortality in hospitalized patients.
- Be aware that only patients who had been ordered an ECG as part of clinical care could be included, potentially biasing the results.
An institution-wide, computer-based alert system for irregular heart rhythms identified and characterized patients at risk of death, researchers found.
Patients identified by the alert system with a greater than 500 ms corrected interval between the Q and T waves of their ECG cycle had a significantly higher risk of death compared with a QTc interval less than 500 ms (19% versus 5%), reported Michael J. Ackerman, MD, PhD, and colleagues from the Mayo Clinic in Rochester, Minn.
A pro-QTc (c=corrected) risk score for mortality, which takes into account clinical diagnoses, lab abnormalities, and medications known to influence the QT interval, among other risk factors, was an independent predictor of death (HR 1.18, 95% CI 1.05 to 1.32, P=0.006), according to the study published in the latest edition of the Mayo Clinic Proceedings.
In comparison, the hazard ratio for the risk associated with an additional year of age was 1.02 (95% CI 1.01 to 1.03, P=0.004).
A number of QT-prolonging diagnoses and conditions were included in the pro-QTc risk score. For each diagnosis or condition, patients received a score of 1. Those with a score of 4 or greater had significantly higher mortality than did patients with a pro-QTc score less than 4 (log-rank P<0.001).
A total of 99% of the study population had a pro-QT score of 1 or greater. The mean pro-QT score was 3.1 (ranging from 0 to 9).
Medications and electrolyte abnormalities were the primary drivers of increased pro-QTc scores. The higher the score, the greater the risk of death.
Antidepressants were the most common QT-prolonging medication among the study population, followed by antiarrhythmics and antibiotics/antifungals. The authors described a “QT perfect storm” that included the potentially lethal combination of antidepressants with QT-prolonging antibiotics on top of concomitant electrolyte abnormalities. They emphasized the importance of being aware of such clinical scenarios.
QT-prolonging medications can be changed and other QT-prolonging stressors can be reduced when physician awareness is raised, the researchers said.
Since 2005, the FDA has required drugs to be evaluated in a Thorough QT (TQT) study to determine their effect on the QT interval. In fact, the most common reason for a drug to be withdrawn from the market is because of their QT-prolongation properties.
However, more than 100 drugs now on the market are known to cause QT prolongation or at least have the potential to cause the syndrome — and they cross all healthcare disciplines. “Yet, the average healthcare professional’s awareness of QTc as a predictor of death is lagging,” Ackerman and colleagues wrote.
When the American Heart Association and the American College of Cardiology called attention to the need to identify patients who are vulnerable to QT prolongation early in their hospital experience, the Mayo researchers decided to develop and implement the QT alert system.
The electronic alert goes to the ordering physicians, and they are encouraged to visit the website AskMayoExpert “to inform and guide them regarding the potential significance of this electrocardiographic (ECG) finding.”
For the study, researchers reviewed slightly more than 81,000 ECGs from 52,579 unique patients who were treated at the Mayo Clinic between November 2010 and June 2011.
Of these patients, 1,145 (2%) had one or more ECGs that received a QT alert (which was seen by at least one of 654 different physicians), and 470 (41%) of these alerts had an “electrocardiographically isolated QTc of 500 ms or greater.” The latter became the study population.
In the study population, a cardiovascular diagnosis (46%) led the list of most common reasons for hospital admission, followed by infectious and gastrointestinal diseases (13% each).
The study population was significantly younger (mean age 55 versus 61), but the prolonged QTc put them at significantly greater risk of death (log-rank P<0.001).
Of the 87 patients in the study population who died, researchers obtained the death diagnosis for 77 of them. Malignancy topped the list of most frequent diagnosis (26%), followed by cardiovascular death (21%), and infectious disease/sepsis (20%).
Those who died of a malignancy were taking more QT-prolonging medications than those who died of other causes. But researchers noted that they cannot prove causation.
Regarding the cardiovascular deaths, seven occurred suddenly, eight died from progressive heart failure, two from amyloidosis, and one was unspecified.
The study confirms QT as a “potent risk predictor of mortality” and shows that an electronic alert system holds promise for bringing more awareness of QT prolongation on an institution-wide scale.
The study’s retrospective design is one of the limitations, as was the lack of specific data for each condition, researchers said.
Funding for the study came from various sources including the Frederick W. Smith family, the Mayo Clinic Windland Smith Rice Comprehensive Sudden Cardiac Death Program, the South-Eastern Norway Regional Health Authority, and the Center for Heart Failure Research in Oslo, Norway.
Ackerman reported relationships with Transgenomic, Boston Scientific, Medtronic, and St Jude Medical. Transgenomic and Mayo Clinic Health Solutions have a partnership that includes several licensing agreements that pay royalties and are related to the study topic.
From the American Heart Association:
- ACC/AHA/ESC 2006 Guidelines for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death – Full Text
Primary source: Mayo Clinic Proceedings
Haugaa KH, et al “Institution-wide QT alert system identifies patients with a high risk of mortality” Mayo Clin Proc 2013; 88(4): 315-325.
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