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Prevalence of QT Interval Prolongation in Patients Admitted to Cardiac Care Units and Frequency of Subsequent Administration of QT Interval-Prolonging Drugs

A Prospective, Observational Study in a Large Urban Academic Medical Center in the US

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Abstract

Background

Cardiac arrest due to torsades de pointes (TdP) is a rare but catastrophic event in hospitals. Patients admitted to cardiac units are at higher risk of drug-induced QT interval prolongation and TdP, due to a preponderance of risk factors. Few data exist regarding the prevalence of QT interval prolongation in patients admitted to cardiac units or the frequency of administering QT interval-prolonging drugs to patients presenting with QT interval prolongation.

Objective

The aim of this study was to determine the prevalence of Bazett’s-corrected QT (QTc) interval prolongation upon admission to cardiac units and the proportion of patients presenting with QTc interval prolongation who are subsequently administered QT interval-prolonging drugs during hospitalization.

Methods

This was a prospective, observational study conducted over a 1-year period (October 2008–October 2009) in 1159 consecutive patients admitted to two cardiac units in a large urban academic medical centre located in Indianapolis, IN, USA. Patients were enrolled into the study at the time of admission to the hospital and were followed daily during hospitalization. Exclusion criteria were age <18 years, ECG rhythm of complete ventricular pacing, and patient designation as ‘outpatient’ in a bed and/or duration of stay <24 hours. Data collected included demographic information, past medical history, daily progress notes, medication administration records, laboratory data, ECGs, telemetry monitoring strips and diagnostic reports. All patients underwent continuous cardiac telemetry monitoring and/or had a baseline 12-lead ECG obtained within 4 hours of admission. QT intervals were determined manually from lead II of 12-lead ECGs or from continuous lead II telemetry monitoring strips. QTc interval prolongation was defined as ≥470 ms for males and ≥480 ms for females. In both males and females, QTc interval >500 ms was considered abnormally high. A medication was classified as QT interval-prolonging if there were published data indicating that the drug causes QT interval prolongation and/or TdP. Study endpoints were (i) prevalence of QTc interval prolongation upon admission to the Cardiac Medical Critical Care Unit (CMCCU) or an Advanced Heart Care Unit (AHCU); (ii) proportion of patients admitted to the CMCCU/AHCU with QTc interval prolongation who subsequently were administered QT interval-prolonging drugs during hospitalization; (iii) the proportion of these higher-risk patients in whom TdP risk factor monitoring was performed; (iv) proportion of patients with QTc interval prolongation who subsequently received QT-prolonging drugs and who experienced further QTc interval prolongation.

Results

Of 1159 patients enrolled, 259 patients met exclusion criteria, resulting in a final sample size of 900 patients. Patient characteristics: mean (± SD) age, 65 ±15 years; female, 47%; Caucasian, 70%. Admitting diagnoses: heart failure (22%), myocardial infarction (16%), atrial fibrillation (9%), sudden cardiac arrest (3%). QTc interval prolongation was present in 27.9% of patients on admission; 18.2% had QTc interval >500ms. Of 251 patients admitted with QTc interval prolongation, 87 (34.7%) were subsequently administered QT interval-prolonging drugs. Of 166 patients admitted with QTc interval >500ms, 70 (42.2%) were subsequently administered QT interval-prolonging drugs; additional QTc interval prolongation ≥60 ms occurred in 57.1% of these patients.

Conclusions

QTc interval prolongation is common among patients admitted to cardiac units. QT interval-prolonging drugs are commonly prescribed to patients presenting with QTc interval prolongation.

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Acknowledgements

This work was supported in part by a grant from the Lilly Endowment, Inc., to the Purdue University College of Pharmacy, and by National Institutes of Health grant [K08 HL095655] (Dr Overholser).

The funding organizations had no role in the design and conduct of the study, collection, management, analysis and interpretation of data, or preparation, review or approval of the manuscript.

Dr Kovacs has served as an advisor to Eli Lilly & Co., Essentialis, Xenoport, Inc., and Synosia Therapeutics regarding issues related to the QT interval in drug development. All other authors have no conflicts of interest to declare.

Presented at the 59th Annual Scientific Sessions of the American College of Cardiology, 15 March 2010.

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Authors and Affiliations

  1. Department of Pharmacy Practice, College of Pharmacy, Purdue University, W7555 Myers Building, WHS, 1001 West 10th Street, Indianapolis, Indiana, IN 46202, USA

    James E. Tisdale PharmD, Heather A. Wroblewski & Brian R. Overholser

  2. Department of Medicine, School of Medicine, Indiana University, Indianapolis, Indiana, USA

    James E. Tisdale PharmD & Brian R. Overholser

  3. Department of Pharmacy, Indiana University Health Methodist Hospital, Indianapolis, Indiana, USA

    Joanna R. Kingery & Tate N. Trujillo

  4. Krannert Institute of Cardiology, School of Medicine, Indiana University, Indianapolis, Indiana, USA

    Richard J. Kovacs

Authors
  1. James E. Tisdale PharmD
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  2. Heather A. Wroblewski
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  3. Brian R. Overholser
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  4. Joanna R. Kingery
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  5. Tate N. Trujillo
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  6. Richard J. Kovacs
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Correspondence to James E. Tisdale PharmD.

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Tisdale, J.E., Wroblewski, H.A., Overholser, B.R. et al. Prevalence of QT Interval Prolongation in Patients Admitted to Cardiac Care Units and Frequency of Subsequent Administration of QT Interval-Prolonging Drugs. Drug Saf 35, 459–470 (2012). https://doi.org/10.2165/11598160-000000000-00000

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  • DOI: https://doi.org/10.2165/11598160-000000000-00000

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