Background Identifying hospitalized patients at risk for QT interval prolongation could lead to interventions to reduce the risk of torsades de pointes (TdP). 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 (DG). The score was then applied to 300 additional patients in a validation group (VG). Corrected QT (QTc) interval prolongation (defined as QTc > 500 ms and/or an increase of > 60 ms from baseline) occurred in 274 (30.4%) and 90 (30.0%) patients in the DG and VG, respectively. Independent predictors of QTc prolongation included: female (odds ratio [OR], 1.5; 95% confidence interval [CI], 1.1–2.0), diagnosis of myocardial infarction [2.5 (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 (1.0–1.8)], serum K+ < 3.5 mEq/L [2.1 (1.5–2.9)], and admitting QTc > 450 ms [2.3; CI (1.6–3.2)]. Risk scores were developed by assigning points based on Log ORs. Low, moderate and high risk ranges of 0–6, 7–10 and 11–21 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 VG, the incidences of QTc prolongation were 15% (low risk); 37% (moderate risk); 73% (high risk). Conclusions A risk score using easily obtainable clinical variables predicts patients at highest risk for QTc prolongation and may be useful in guiding monitoring and treatment decisions.

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.

Background/Aim: hERG potassium channels enhance tumor invasiveness and breast cancer proliferation. MicroRNA (miRNA) dysregulation during cancer controls gene regulation. The objective of this study was to identify miRNAs that regulate hERG expression in breast cancer. Materials and Methods: Putative miRNAs targeting hERG were identified by bioinformatic approaches and screened using a 3'UTR luciferase assay. Functional assessments of endogenous hERG regulation were made using whole-cell electrophysiology, proliferation assays, and cell-cycle analyses following miRNA, hERG siRNA, or control transfection. Results: miR-362-3p targeted hERG 3'UTR and was associated with higher survival rates in patients with breast cancer (HR=0.39, 95%CI=0.18-0.82). Enhanced miR-362-3p expression reduced hERG expression, peak current, and cell proliferation in cultured breast cancer cells (p<0.05). Conclusion: miR-362-3p mediates the transcriptional regulation of hERG and is associated with survival in breast cancer. The potential for miR-362-3p to serve as a biomarker and inform therapeutic strategies warrants further investigation.