Clinically relevant QTc prolongation due to overridden drug-drug interaction alerts: a retrospective cohort study.

AIMS: To investigate whether, in patients in whom drug-drug interaction (DDI) alerts on QTc prolongation were overridden, the physician had requested an electrocardiogram (ECG), and if these ECGs showed clinically relevant QTc prolongation. METHODS: For all patients with overridden DDI alerts on QTc prolongation during 6 months, data on risk factors for QT prolongation, drug class and ECGs were collected from the medical record. Patients with ventricular pacemakers, patients treated on an outpatient basis, and patients using the low-risk combination of cotrimoxazole and tacrolimus were excluded. The magnitude of the effect on the QTc interval was calculated if ECGs before and after overriding were available. Changes of the QTc interval in these cases were compared with those of a control group using one QTc-prolonging drug. RESULTS: In 33% of all patients with overridden QTc alerts an ECG was recorded within 1 month. ECGs were more often recorded in patients with more risk factors for QTc prolongation and with more QTc overrides. ECGs before and after the QTc override were available in 29% of patients. Thirty-one percent of patients in this group showed clinically relevant QTc prolongation with increased risk of torsades de pointes or ventricular arrhythmias. The average change in QTc interval was +31 ms for cases and -4 ms for controls. CONCLUSIONS: Overriding the high-level DDI alerts on QTc prolongation rarely resulted in the preferred approach to subsequently record an ECG. If ECGs were recorded before and after QTc overrides, clinically relevant QTc prolongation was found in one-third of cases. ECG recording after overriding QTc alerts should be encouraged to prevent adverse events.

Prevention of inappropriate therapy in implantable cardioverter-defibrillators: results of a prospective, randomized study of tachyarrhythmia detection algorithms.

OBJECTIVES: The purpose of this randomized study was to investigate the performance of single- and dual-chamber tachyarrhythmia detection algorithms. BACKGROUND: A proposed benefit of dual-chamber implantable cardioverter-defibrillators (ICDs) is improved specificity of tachyarrhythmia detection. METHODS: All ICD candidates received a dual-chamber ICD and were randomized to programmed single- or dual-chamber detection. Of 60 patients (47 male, age 58 +/- 14 years, left ventricular ejection fraction 30%), 29 had single-chamber and 31 had dual-chamber settings. The detection results were corrected for multiple episodes within a patient with the generalized estimating equations method. RESULTS: A total of 653 spontaneous arrhythmia episodes (39 patients) were classified by the investigators; 391 episodes were ventricular tachyarrhythmia (32 patients). All episodes of ventricular tachyarrhythmias were appropriately detected in both settings. In 25 patients, 262 episodes of atrial tachyarrhythmias were recorded. Detection was inappropriate for 109 atrial tachyarrhythmia episodes (42%, 18 patients). Rejection of atrial tachyarrhythmias was not significantly different between both groups (p = 0.55). Episodes of atrial flutter/tachycardia were significantly more misclassified (p = 0.001). Overall, no significant difference in tachyarrhythmia detection (atrial and ventricular) between both settings was demonstrated (p = 0.77). CONCLUSIONS: The applied detection criteria in dual-chamber devices do not offer benefits in the rejection of atrial tachyarrhythmias. Discrimination of atrial tachyarrhythmias with a stable atrioventricular relationship remains a challenge.

Clinical variables predicting inappropriate use of implantable cardioverter-defibrillator in patients with coronary heart disease or nonischemic dilated cardiomyopathy.

Inappropriate therapy is a common clinical problem in recipients of implantable cardioverter-defibrillators (ICDs). The present study evaluated whether clinical characteristics could predict inappropriate ICD therapy due to atrial tachyarrhythmias in a series of 260 patients.

Outcome in patients with an ICD incorporating cardiac resynchronisation therapy: differences between primary and secondary prophylaxis.

BACKGROUND: The incidence of ventricular tachyarrhythmias in ICD patients with cardiac resynchronisation therapy (CRT-D) is not well studied. AIM: To analyse event free survival in CRT-D patients with a primary or a secondary prophylactic ICD indication. METHODS: Prospective, single centre. Eighty-six patients, 44% with a primary prophylactic indication. Actuarial event-free rates for mortality and arrhythmias were calculated. RESULTS: Baseline clinical characteristics were not significantly different between primary and secondary prophylaxis. Primary prophylaxis patients were more likely to be in NYHA class III. Over 21 months, 724 ventricular events with therapy occurred in 36 patients (42%). The actuarial event-free rates, at 1 and 3 years, from appropriate ICD therapy were higher (P<0.001) for primary (79.0% and 67.8%) than for secondary prophylaxis (45.6% and 27.0%). Appropriate ICD therapy occurred more in NYHA class II compared to class III (P=0.016). Underlying disease (ischemic versus non-ischemic) and functional class did not play a role in multivariate analysis. CONCLUSION: Important arrhythmic events in patients with heart failure, and CRT-D occur at a very high rate when the indication is secondary prophylaxis. Patients with primary prophylaxis have an annual event rate of 10%, even though they tend to have a worse heart failure class.