The Adjunct Role of Ranolazine to Refractory Ischemic Ventricular Tachycardia Following Palliative Ablation: Single-Center Experience

Introduction

Despite significant improvements in the field of catheter ablation for scar-based ventricular tachycardia (VT), the availability of antiarrhythmic agents have lagged behind. Patients with sustained VT will commonly present with implantable cardioverter-defibrillator (ICD) shocks. Immediate therapy centers on initiation of drug therapy. The mainstay of arrhythmia suppression is typically with amiodarone, and less often sotalol.^1,2 When these agents are not effective in preventing VT, other agents can be added in combination, but ablation therapy is usually considered the next step.³

A clinical conundrum occurs when catheter ablation cannot eliminate all the active VT exit sites. Recurrence of “clinical” VT or the appearance of new morphologies is common.

The procedures are not without risk, and the patients are often considered to be high risk given poor left ventricular systolic function and other comorbidities.³ Hence, there exists a reluctance to submit to quickly repeat the index procedure. Given the few medical alternatives to treat post-ablation VT, some authors have resorted to the use of ranolazine, a delayed sodium channel blocker, for this purpose. In this brief report, we discuss our experience with ranolazine as complementary therapy to unsuccessful antiarrhythmic and ablation therapy.

Case Description

A 67-year-old woman, with a remote anterior wall infarction and left ventricular ejection fraction of 20%, presented with intractable VT and numerous appropriate shocks. Despite intravenous and oral amiodarone, the patient continued to experience recurrent monomorphic VT and therapy (Figure 1). Notably, the episodes were initiated by narrow complex unifocal premature ventricular contractions (PVCs), suggesting that Purkinje-fiber triggering could be responsible.^4-6 Coronary angiography excluded active ischemia. The patient was then taken for a palliative VT ablation with the objectives of targeting the responsible reentrant tracts and the culprit ectopy. A preoperative resting myocardial perfusion scan demonstrated an extensive anterior wall scar extending to the apex. This modality is used to assist with defining the scar borders while voltage mapping (Figure 2).⁷

The procedure was conducted under general anesthesia. The clinical PVCs were observed to occur spontaneously. During programmed stimulation, multiple morphologies were the rule, with pleomorphic VT degenerating into fibrillation and requiring countershock for termination. Given the hemodynamic instability, substrate and pace mapping were undertaken. Voltage mapping identified a “horseshoe-shaped” channel at the inferior apical region prior to a completely scarred zone (Figure 3). Pace mapping was 12/12 inside the channel. Moreover, short bursts of the clinical VT were noted. High-frequency, low-amplitude electrograms suggestive of injured Purkinje potentials were seen (Figure 4). Ablation through the channel was done, terminating the clinical VT without recurrence and with suppression of ectopy. Given the overall condition of the patient, aggressive ablation of all morphologies was deferred and amiodarone 400 mg daily was continued.

After two weeks, the patient presented with ICD shocks from VT with a different morphology and shorter cycle length. Mexiletine was introduced in escalating dosage without success, and the patient continued to experience frequent VT refractory to antitachycardia pacing, necessitating shocks for termination. Ultimately the latter was discontinued, and off-label ranolazine was initiated and uptitrated to a maximum dosage of 1000 mg every 12 hours, while amiodarone dosage was tapered to 200 mg daily. The introduction of ranolazine led to no further VT. After a ten-month follow-up period, the patient has been completely free of any VT, including ectopy and nonsustained ventricular arrhythmia (Figure 5).

Discussion

Electrical storm can be a daunting management problem, in particular when catheter ablation cannot eliminate all potential circuits or triggers. This dilemma gains further complexity when antiarrhythmics are ineffective. There exists nonrandomized and anecdotal evidence supporting the use of ranolazine for reduction of VT, albeit not necessarily for electrical storm.⁸ Pharmacologically, ranolazine is a delayed sodium channel blocker with an indication to treat chronic angina.⁹ However, during the MERLIN-TIMI 36 trial, there appeared to be a lower incidence of ventricular arrhythmia, and this inspired additional studies to further determine additional use of the drug.^10-11 Nevertheless, more data is needed to better define ranolazine’s indication in the medical treatment of ventricular tachycardia. Currently, the NIH-funded RAID study is underway. RAID is a randomized multicenter clinical trial evaluating the use of ranolazine in reducing the risk of ventricular arrhythmia and death in patients with ICDs.¹²

Conclusion

In this case, add-on delayed sodium channel blockade with ranolazine eliminated VT recurrence in a patient with advanced ischemic cardiomyopathy following ineffective medical and ablative interventions. With accumulative experience, the role of this agent will become more clear.

Disclosures: Dr. Perzanowski reports he is an investigator in the RAID trial. Ms. Dunbar and Ms. Bischoff have no conflicts of interest to report regarding the content herein.

References

1. Schleifer JW, Sorajja D, Shen WK. Advances in the pharmacologic treatment of ventricular arrhythmias. Expert Opin Pharmacother. 2015;29:1-15.
2. Williams ES, Viswanathan MN. Current and emerging antiarrhythmic drug therapy for ventricular tachycardia. Cardiol Ther. 2013;2:27-46.
3. Natale, A, Raviele A. Venice Chart International Consensus document on ventricular tachycardia/ventricular fibrillation ablation. J Cardiovasc Electrophysiol. 2010;21:339-379.
4. Marrouche NF, Verma A, Wazni O, et al. Mode of initiation and ablation of ventricular fibrillation storms in patients with ischemic cardiomyopathy. J Am Coll Cardiol. 2004;43:1715-1720.
5. Murata H, Miyauchi Y, Hayashi M, et al. Clinical and Electrocardiographic Characteristics of Electrical Storms Due to Monomorphic Ventricular Tachycardia Refractory to Intravenous Amiodarone. Circ J. 2015;79:2130-2137.
6. Bänsch D, Oyang F, Antz M, et al. Successful catheter ablation of electrical storm after myocardial infarction. Circulation. 2003;108:3011-3016.
7. Perzanowski C, Zilo P, Weiss DN. Myocardial perfusion scan as an adjunct to voltage mapping for VT ablation. Europace. 2008;10(Suppl):i188.
8. Bunch TJ, Mahapatra S, Murdock D, et al. Ranolazine reduces ventricular tachycardia burden and ICD shocks in patients with drug-refractory ICD shocks. Pacing Clin Electrophysiol. 2011;34:1600-1606.
9. Wilson SR, Scirica BM, Braunwald E, et al. Efficacy of ranolazine in patients with chronic angina observations from the randomized, double-blind, placebo-controlled MERLIN-TIMI (Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST-Segment Elevation Acute Coronary Syndromes) 36 Trial. J Am Coll Cardiol. 2009;53:1510-1516.
10. Scirica BM, Morrow DA, Hod H, et al. Effect of ranolazine, an antianginal agent with novel electrophysiological properties, on the incidence of arrhythmias in patients with non ST-segment elevation acute coronary syndrome: results from the Metabolic Efficiency With Ranolazine for Less Ischemia in Non ST-Elevation Acute Coronary Syndrome Thrombolysis in Myocardial Infarction 36 (MERLIN-TIMI 36) randomized controlled trial. Circulation. 2007;116:1647-1652.
11. Yeung E, Krantz MJ, Schuller JL, Dale RA, Haigney MC. Ranolazine for the suppression of ventricular arrhythmia: a case series. Ann Noninvasive Electrocardiol. 2014;19:345-350.
12. Ranolazine Implantable Cardioverter-Defibrillator Trial (RAID). Clinicaltrials.gov. Published December 30, 2015. Available online at https://clinicaltrials.gov/ct2/show/NCT01215253. Accessed March 10, 2016.