Joanna R. Kingery

Development and Validation of a Risk Score to Predict QT Interval Prolongation in Hospitalized Patients

Background—Identifying hospitalized patients at risk for QT interval prolongation could lead to interventions to reduce the risk of torsades de pointes. Our objective was to develop and validate a risk score for QT prolongation in hospitalized patients. Methods and Results—In this study, in a single tertiary care institution, consecutive patients (n=900) admitted to cardiac care units comprised the risk score development group. The score was then applied to 300 additional patients in a validation group. Corrected QT (QTc) interval prolongation (defined as QTc>500 ms or an increase of >60 ms from baseline) occurred in 274 (30.4%) and 90 (30.0%) patients in the development group and validation group, respectively. Independent predictors of QTc prolongation included the following: female (odds ratio, 1.5; 95% confidence interval, 1.1–2.0), diagnosis of myocardial infarction (2.4 [1.6–3.9]), sepsis (2.7 [1.5–4.8]), left ventricular dysfunction (2.7 [1.6–5.0]), administration of a QT-prolonging drug (2.8 [2.0–4.0]), ≥2 QT-prolonging drugs (2.6 [1.9–5.6]), or loop diuretic (1.4 [1.0–2.0]), age >68 years (1.3 [1.0–1.9]), serum K+ <3.5 mEq/L (2.1 [1.5–2.9]), and admitting QTc >450 ms (2.3; confidence interval [1.6–3.2]). Risk scores were developed by assigning points based on log odds ratios. Low-, moderate-, and high-risk ranges of 0 to 6, 7 to 10, and 11 to 21 points, respectively, best predicted QTc prolongation (C statistic=0.823). A high-risk score ≥11 was associated with sensitivity=0.74, specificity=0.77, positive predictive value=0.79, and negative predictive value=0.76. In the validation group, the incidences of QTc prolongation were 15% (low risk); 37% (moderate risk); and 73% (high risk). Conclusions—A risk score using easily obtainable clinical variables predicts patients at highest risk for QTc interval prolongation and may be useful in guiding monitoring and treatment decisions.

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

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

Effectiveness of a Clinical Decision Support System for Reducing the Risk of QT Interval Prolongation in Hospitalized Patients

Background—We evaluated the effectiveness of a computer clinical decision support system (CDSS) for reducing the risk of QT interval prolongation in hospitalized patients. Methods and Results—We evaluated 2400 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=1200) and after (n=1200) 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). Conclusions—A computer 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 hospitalized patients with torsades de pointes risk factors.

Enhanced Sensitivity to Drug-Induced QT Interval Lengthening in Patients With Heart Failure Due to Left Ventricular Systolic Dysfunction

Patients with heart failure (HF) are at increased risk for drug‐induced torsades de pointes (TdP) due to unknown mechanisms. Our objective was to determine if sensitivity to drug‐induced QT interval lengthening is enhanced in patients with HF. In this multicenter, prospective study, 15 patients with atrial fibrillation or flutter requiring conversion to sinus rhythm were enrolled: 6 patients with New York Heart Association class II to III HF (mean ejection fraction [EF], 30% ± 9%), and 9 controls (mean EF, 53% ± 6%). Patients received ibutilide 1 mg intravenously. Blood samples and 12‐lead electrocardiograms were obtained prior to and during 48 hours postinfusion. Serum ibutilide concentrations at 50% maximum effect on Fridericia‐corrected QT (QTF) intervals (EC50) were determined, and areas under the effect (QTF interval vs time) curves (AUECs) were calculated. Ibutilide concentration—QTF relationships were best described by a sigmoidal Emax model with a hypothetical effect compartment. Median [interquartile range] AUEC from 0 to 4 hours was larger in the HF group than in controls (1.86 [1.86–1.93] vs 1.82 [1.81–1.84] s·h; P = .04). Median EC50 was lower in the HF group (0.48 [0.46–0.49] vs 1.85 [1.10–3.23] μg/L; P = .008). Sensitivity to drug‐induced QT interval lengthening is enhanced in patients with systolic HF, which may contribute to the increased risk of drug‐induced TdP.

Pharmacokinetics of ibutilide in patients with heart failure due to left ventricular systolic dysfunction

Study Objective. To assess whether the increased risk of ibutilide‐induced torsade de pointes in patients with heart failure may be due to increased ibutilide exposure, we sought to determine if the pharmacokinetics of ibutilide are altered in patients with heart failure due to left ventricular systolic dysfunction.

High Risk of QT Interval Prolongation and Torsades de Pointes Associated with Intravenous Quinidine Used for Treatment of Resistant Malaria or Babesiosis

ABSTRACT Cardiac toxicity may be associated with drugs used for malaria. Torsades de pointes (TdP) is a well-known adverse effect of quinidine when used for atrial fibrillation. Intravenous quinidine doses for resistant malaria are 2 to 3 times higher than those used for arrhythmias. Among 6 patients receiving quinidine for malaria or babesiosis, 4 developed QT interval prolongation and 2 experienced TdP. Clinicians should be aware that recommended doses of quinidine for malaria carry a high TdP risk.

Patient Safety Coalition: A Focus on Heart Failure.

Indianapolis Coalition for Patient Safety, Inc engaged a citywide effort to reduce hospital readmissions of patients diagnosed with heart failure within 30 days of discharge. An innovative collaboration among interdisciplinary representatives of hospitals, skilled nursing facilities, and home care agencies resulted in reduction in readmissions for patients with heart failure.