Despite its multiple well-described side effects, amiodarone remains the drug of choice for arrhythmias refractory to the other antiarrhythmic drugs (AAD). While it is primarily a class III antiarrhythmic drug blocking the potassium rectifier currents responsible for myocyte repolarization during phase 3 of the cardiac action potential, amiodarone also acts as a beta-adrenergic receptor blocker, calcium channel blocker, and sodium channel blocker, rendering its activity superior to the other antiarrhythmic drugs.^1,2 Specifically, amiodarone is the drug of choice for ischemic ventricular tachycardia (VT) both as acute and chronic therapy.³

In the era of VT ablation, and especially the breakthrough of ablation mediated by anatomical and functional substrate mapping in sinus rhythm rather than during sustained VT induction, there is still a knowledge gap regarding the role of amiodarone prior to VT ablation and its potential effect on the long-term outcome of the procedure. Substrate mapping in sinus rhythm helps in the identification of local abnormal ventricular activities (LAVAs), low-voltage fractionated electrograms (EGMs), late potentials (LPs) and deceleration zones.^4,5 To increase the likelihood of procedural success, theoretically all the areas with abnormal conduction must be mapped and ablated. Whether amiodarone treatment pre-ablation temporarily masks these areas during the procedure and modifies the procedural endpoint was the scope of Di Biase et al.'s publication in Heart Rhythm.⁶

In their observational study, the investigators published the findings from 134 consecutive patients undergoing ischemic VT ablation for recurrent VT despite AAD treatment. The patients were divided into two groups based on the pre-ablation treatment with amiodarone: the "on" group (n = 84) consisted of patients who received amiodarone within 8 weeks of the procedure, and the "off" group (n = 50) consisted of patients who did not receive amiodarone for 8 weeks prior to the procedure. The latter group was treated with mexiletine, sotalol, or quinidine for up to 48 hours pre-procedure. Both groups' baseline characteristics were similar. Procedural characteristics were different. Longer procedural and fluoroscopy times were required for the "off" group, and more patients from this group required epicardial access compared to the "on" group. Patients in the "on" group required significantly more aggressive programmed stimulation for VT induction. Similarly, fewer LAVAs and LPs were identified in the "on" group as compared to the "off" group, portending a potential drawback of the use of amiodarone pre-ablation; the endpoint may be temporarily falsely achieved. This may explain the 100% relative risk increase in the VT recurrence between the patients from the "on" group and those from the "off" group (44% vs. 22%, respectively; log rank, P = 0.013) after 23.9 ± 11.6 months.

The use of AAD prior to atrial fibrillation (AF) ablation has been studied and has similarly shown that they reduce the number of identified complex fractionated EGMs; however, in AF ablation, this use did not result in a change in ablation outcomes.⁷ For the first time, concomitant use of AAD during or just prior to VT ablation in ischemic cardiomyopathy is addressed and actually poses a question whether AAD use leads to acute procedural success but worse long-term outcome.

As acknowledged by the study investigators, this is an observational study leaving room for selection bias. In addition, it is a single-center study done at a highly specialized, high-volume, high-expertise referral center, and hence generalizing this practice and changing the guideline needs more solid evidence. A randomized multicenter trial is still lacking for this matter. Furthermore, although the patients' baseline characteristics are similar, one can still assume that the patients on amiodarone prior to ablation are sicker patients and may have failed attempts to discontinue amiodarone prior to ablation. The study did not mention the average number of VT recurrences in the patients.

In conclusion, this study constitutes a major building block in the literature of VT ablation in ischemic cardiomyopathy, and stimulates researchers to look more closely into the use of AAD prior to VT ablation. Moreover, it illustrates the previously accepted success rates of VT ablation which was around 70% (while the included patients in the previous studies were frequently on amiodarone prior to the procedure).3 If the study results are further validated, it will provide a major explanation of the relatively high rate of recurrence of VT post-ablation. Lastly, although the presumed half-life of amiodarone is 58 days, it is known that antiarrhythmic effects of amiodarone may last 1-3 months post discontinuation.

References

1. Florek JB, Girzadas D. Amiodarone. In: StatPearls. Treasure Island: StatPearls Publishing; 2021:[Internet].
2. Soar J, Perkins GD, Maconochie I, et al. European Resuscitation Council guidelines for resuscitation: 2018 update – Antiarrhythmic drugs for cardiac arrest. Resuscitation 2019;134:99-103.
3. Cronin EM, Bogun FM, Maury P, et al. 2019 HRS/EHRA/APHRS/LAHRS expert consensus statement on catheter ablation of ventricular arrhythmias. Europace 2019;21:1143-4.
4. Irie T, Yu R, Bradfield JS, et al. Relationship between sinus rhythm late activation zones and critical sites for scar-related ventricular tachycardia: systematic analysis of isochronal late activation mapping. Circ Arrhythm Electrophysiol 2015;8:390-9.
5. Briceño DF, Romero J, Villablanca PA, et al. Long-term outcomes of different ablation strategies for ventricular tachycardia in patients with structural heart disease: systematic review and meta-analysis. Europace 2018;20:104-15.
6. Di Biase L, Romero J, Du X, et al. Catheter ablation of ventricular tachycardia in ischemic cardiomyopathy: Impact of concomitant amiodarone therapy on short- and long-term clinical outcomes. Heart Rhythm 2021;18:885-93.
7. Miwa Y, Minamiguchi H, Bhandari AK, Cannom DS, Ho IC. Amiodarone reduces the amount of ablation during catheter ablation for persistent atrial fibrillation. Europace 2014;16:1007-14.

Clinical Topics: Arrhythmias and Clinical EP, Dyslipidemia, Heart Failure and Cardiomyopathies, Noninvasive Imaging, EP Basic Science, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias, Lipid Metabolism, Novel Agents, Statins, Nuclear Imaging, Geriatric Cardiology

Keywords: Anti-Arrhythmia Agents, Sotalol, Quinidine, Mexiletine, Calcium Channel Blockers, Amiodarone, Atrial Fibrillation, Sodium Channel Blockers, Action Potentials, Risk, Selection Bias, Potassium, Calcium Channels, Deceleration, Tachycardia, Ventricular, Pharmaceutical Preparations, Cardiomyopathies, Fluoroscopy, Muscle Cells, Referral and Consultation, Receptors, Adrenergic, beta

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