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Background: There are limited options for patients who present with antiarrhythmic-drug (AAD)-refractory ventricular tachycardia (VT) with recurrent implantable cardioverter defibrillator (ICD) shocks. Ranolazine is a drug that exerts antianginal and antiischemic effects and also acts as an antiarrhythmic in isolation and in combination with other class III medications. Ranolazine may be an option for recurrent AAD-refractory ICD shocks secondary to VT, but its efficacy, outcomes, and tolerance are unknown. Methods and Results: Twelve patients (age 65 ± 9.7 years) were treated with ranolazine. Eleven (92%) were male, and 10 (83%) had ischemic heart disease with an average ejection fraction of 0.34 ± 0.13. All patients were on a class III AAD (11 amiodarone, one sotalol), with six (50%) receiving mexilitene or lidocaine. Five patients had a prior ablation and two were referred for a VT ablation at the index presentation. The QRS increased nonsignificantly from 128 ± 31 ms to 133 ± 31 ms, and the QTc increased nonsignificantly from 486 ± 32 ms to 495 ± 31 ms after ranolazine initiation. Over a follow-up of 6 ± 6 months, 11 (92%) patients had a significant reduction in VT and no ICD shocks were observed. VT ablation was not required in those referred. In two patients, gastrointestinal side effects limited long-term use. Of these two patients, one died due to progressive heart failure. In one patient, severe hypoglycemia limited dosing to 500 mg daily, but this was sufficient for VT control. Conclusion: Ranolazine proved effective in reducing VT burden and ICD shocks in patients with AAD-refractory VT. Ranolazine should be further tested for this indication and considered for clinical application when other options have proven ineffective. (PACE 2011; 34:1600-1606) [ABSTRACT FROM AUTHOR]