Amiodarone-Sotalol Combination for Refractory Ischemic Ventricular Tachycardia: A Valid Approach?

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.

Case Description

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.

Discussion    

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 I_Na) and the rapid delayed rectifier potassium current (I_Kr).^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. 

Conclusion

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.   

References

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