Ventricular tachyarrhythmias are the most common cause of sudden cardiac death (SCD) in the post-MI population.1 The risk is highest in the first 30 days after MI among patients with left ventricular dysfunction, heart failure, or both.2 Antiarrhythmic medications are typically used as an adjunct to implantable cardioverter-defibrillators (ICDs) to prevent recurrent ventricular tachycardia (VT) and SCD.
However, studies have not shown that antiarrhythmic agents improve survival post MI; for example, amiodarone has a neutral effect on survival. Catheter ablation can be useful for spontaneous and sustained VT, and may reduce frequency of events. Antiarrhythmic support is often used. ICDs are the usual course of action in this scenario, but only after 40 days post-revascularization.3 There are very few studies in the literature about the effective use of an antiarrhythmic combination. Due to their mechanism of action, antiarrhythmic medications are known to have various side effects.
For this purpose, we report the effective use of an amiodarone plus sotalol combination for refractory ischemic VT in a post-CABG patient refractory to multiple antiarrhythmic medications and radiofrequency ablation. The recurrent VT finally resolved with amiodarone-sotalol therapy; therefore, this combination might be a potential option for refractory ischemic VT.
A morbidly obese 54-year-old diabetic, hypertensive female underwent two-vessel coronary artery bypass grafting (CABG). She developed sustained VT on the second and fourth post-operative days (Figure 1) requiring electrical cardioversion and IV amiodarone. There was one dominant VT morphology. The patient also developed renal failure requiring hemodialysis, which was later resolved. Persistent atrial fibrillation (AFib) with rapid conduction was also noted on the third postoperative day. The patient continued to have significant symptomatic burden of sustained monomorphic VT (SMVT) even on fully loaded amiodarone; therefore, IV lidocaine was introduced.
Despite being on an amiodarone-lidocaine combination, recurrent episodes of SMVT continued to develop with poor hemodynamics. Lidocaine was discontinued due to neurotoxicity. The patient was referred for palliative VT ablation. During EP study, it was determined that the VT critical isthmus involved an epicardial circuit. It was determined for the best interest of the patient to avoid an epicardial approach at the time. Off-label ranolazine was then added, owing to its antiarrhythmic property of being a known late sodium current blocker.4,5
An ICD implant was contraindicated due to an ongoing sternal wound infection with Staphylococcus epidermidis and Mycobacterium fortuitum. One-week post-ablation, the patient experienced further episodes of SMVT, again requiring electrical cardioversion. In view of limited options, sotalol was started as an off-label combination to amiodarone based on observations of anecdotal experiences. Careful monitoring for QT prolongation was performed (Figure 2).
Twelve months after the patient was treated with this combination, there has been no further episode of VT. Notably, the patient has had extensive inpatient monitoring during multiple hospitalizations related to sternal wound infection. An ICD was contraindicated due to this sternal wound infection, and due to the patient’s body habitat, a wearable defibrillator would not fit this patient.
Recurrent SMVT is associated with increased mortality and hospital admissions as well as reduced quality of life after ICD shocks.6-8 Antiarrhythmic agents and/or catheter ablation are used to reduce recurrences and control incessant VT and electrical storms. Our approach to combination therapy using two antiarrhythmic medications with different mechanisms, amiodarone and sotalol, has been successful after long-term follow-up and well tolerated. No adverse effects have been noted.
With the exception of β blockers, currently available antiarrhythmic drugs have not been shown in randomized clinical trials to be effective in the primary management of patients with life-threatening ventricular arrhythmias or in the prevention of SCD.9 Some studies with amiodarone have shown favorable results, but this is not a consistent finding.10,11,19
Among membrane-active antiarrhythmic drugs that block cardiac ion channels, Class 1c sodium channel blockers such as flecainide and propafenone are contraindicated in patients with structural heart disease due to their negative inotropic and proarrhythmic effects. Flecainide increases mortality when used in patients with asymptomatic or mildly symptomatic ventricular arrhythmia after myocardial infarction, according to the Cardiac Arrhythmia Suppression Trial (CAST).12 Primary potassium channel blockers such as sotalol and dofetilide prolong repolarization and increase risk of torsade de pointes. Careful monitoring for QT prolongation is needed.
Amiodarone is a broad-spectrum antiarrhythmic agent that blocks sodium and potassium channels, thereby inhibiting or terminating ventricular arrhythmias by influencing automaticity and re-entry. Both amiodarone and sotalol reduce ventricular and atrial arrhythmias that can lead to ICD shocks.13 Amiodarone is the most effective; however, its adverse effects (e.g., prominently thyroid, lung, liver, and neurological effects) restrict long-term use in more than 20% of patients.13 Amiodarone also prolongs QTc. In light of the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT), amiodarone lacks survival benefit in patients with LVEF ≤35%.4,20
Combination therapy has not been widely studied. There have been very few studies showing combined use of sodium channel blockers and potassium channel blockers (e.g., mexiletine and sotalol, or flecainide/propafenone and amiodarone) in patients with drug-refractory ventricular arrhythmias.4,14 Ranolazine is a medication that exerts antianginal and anti-ischemic effects, and also has antiarrhythmic property by inhibiting multiple ion channels, including the late phase of the inward sodium channel (late INa) and the rapid delayed rectifier potassium current (IKr).4,5 Bunch et al reported in a multicenter case series that ranolazine in combination with other antiarrhythmic agents was proven to be effective in reducing VT burden and ICD shocks in drug-refractory VT.15 However, this was not the case in our patient. One retrospective study also suggested the efficacy of combination therapy with lidocaine and amiodarone in refractory ventricular arrhythmias.16 The drawback of this combination is the interaction between these two resulting in lidocaine toxicity (most commonly neurologic) likely secondary to the inhibition of cytochrome P-4503A4 (CYP3A4) by amiodarone and/or by its main metabolite N-monodesethylamiodarone (DEA).17,18 This might explain the agitation experienced by our patient after starting IV lidocaine.
We report the use of an amiodarone-sotalol combination to successfully control incessant VT. There were no adverse effects, and the patient has been VT-free for one year. Further studies expanding the potential use of this combination therapy (amiodarone and sotalol) are needed.
Disclosures: The authors have no conflicts of interest to report regarding the content herein.
- Zipes DP, Camm AJ, Borggrefe M, et al. ACC/AHA/ESC 2006 Guidelines for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death: a report of the American College of Cardiology/American Heart Association Task Force and the European Society of Cardiology Committee for Practice Guidelines (writing committee to develop Guidelines for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death): developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society. Circulation. 2006;114:e385-484.
- Solomon SD, Zelenkofske S, McMurray JJ, et al. Sudden death in patients with myocardial infarction and left ventricular dysfunction, heart failure, or both. N Engl J Med. 2005;352:2581.
- Russo AM, Stainback RF, Bailey SR, et al. ACCF/HRS/AHA/ASE/HFSA/SCAI/SCCT/SCMR 2013 appropriate use criteria for implantable cardioverter-defibrillators and cardiac resynchronization therapy: a report of the American College of Cardiology Foundation appropriate use criteria task force, Heart Rhythm Society, American Heart Association, American Society of Echocardiography, Heart Failure Society of America, Society for Cardiovascular Angiography and Interventions, Society of Cardiovascular Computed Tomography, and Society for Cardiovascular Magnetic Resonance. Heart Rhythm. 2013;10:e11-58.
- Wagner WL, Manz M, Lüderitz B. [Combination of sotalol with the class I B substances mexiletine or tocainide in complex ventricular extrasystole]. Z Kardiol. 1987;76(5):296-302.
- Reddy BM, Weintraub HS, Schwartzbard AZ. Ranolazine: a new approach to treating an old problem. Tex Heart Inst J. 2010;37:641-647.
- Aliot EM, Stevenson WG, Almendral-Garrote JM, et al. EHRA/HRS Expert Consensus on Catheter Ablation of Ventricular Arrhythmias: developed in a partnership with the European Heart Rhythm Association (EHRA), a Registered Branch of the European Society of Cardiology (ESC), and the Heart Rhythm Society (HRS); in collaboration with the American College of Cardiology (ACC) and the American Heart Association (AHA). Europace. 2009;11:771-817.
- Poole JE, Johnson GW, Hellkamp AS, et al. Prognostic importance of defibrillator shocks in patients with heart failure. N Engl J Med. 2008;359:1009-1017.
- Sesselberg HW, Moss AJ, McNitt S, et al. Ventricular arrhythmia storms in postinfarction patients with implantable defibrillators for primary prevention indications: a MADIT-II substudy. Heart Rhythm. 2007;4:1395-1402.
- Priori SG, Blomström-Lundqvist C, Mazzanti A, et al. 2015 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: The Task Force for the Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death of the European Society of Cardiology (ESC). Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC). Eur Heart J. 2015;36(41):2793-2867.
- Effect of prophylactic amiodarone on mortality after acute myocardial infarction and in congestive heart failure: meta-analysis of individual data from 6500 patients in randomised trials. Amiodarone Trials Meta-Analysis Investigators. Lancet. 1997;350(9089):1417-1424.
- Boutitie F, Boissel JP, Connolly SJ, et al. Amiodarone interaction with β-blockers: analysis of the merged EMIAT (European Myocardial Infarct Amiodarone Trial) and CAMIAT (Canadian Amiodarone Myocardial Infarction Trial) databases. The EMIAT and CAMIAT Investigators. Circulation. 1999;99(17):2268-2275.
- The Cardiac Arrhythmia Suppression Trial (CAST) Investigators. Preliminary report: effect of encainide and flecainide on mortality in a randomized trial of arrhythmia suppression after myocardial infarction. N Engl J Med. 1989;321:406-412.
- Connolly SJ, Dorian P, Roberts RS, et al. Comparison of beta-blockers, amiodarone plus beta-blockers, or sotalol for prevention of shocks from implantable cardioverter defibrillators: the OPTIC Study: a randomized trial. JAMA. 2006;295:165-171.
- Wichter T, Borggrefe M, Haverkamp W, Chen X, Breithardt G. Efficacy of antiarrhythmic drugs in patients with arrhythmogenic right ventricular disease. Results in patients with inducible and noninducible ventricular tachycardia. Circulation. 1992;86(1):29-37.
- 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(12):1600-1606.
- Yoshie K, Tomita T, Takeuchi T, et al. Renewed impact of lidocaine on refractory ventricular arrhythmias in the amiodarone era. Int J Cardiol. 2014;176(3):936-940.
- Ha HR, Candinas R, Stieger B, Meyer UA, Follath F. Interaction between amiodarone and lidocaine. J Cardiovasc Pharmacol. 1996;28(4):533-539.
- Siegmund JB, Wilson JH, Imhoff TE. Amiodarone interaction with lidocaine. J Cardiovasc Pharmacol. 1993;21(4):513-515.
- Singh BN, Singh SN, Reda DJ, et al. Amiodarone versus sotalol for atrial fibrillation. N Engl J Med. 2005;352(18):1861-1872.
- Bardy GH, Lee KL, Mark DB, et al. Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure. N Engl J Med. 2005;352(3):225-237.