Author + information
- Published online March 1, 2017.
- Edward P. Gerstenfeld, MD∗ ( and )
- Tomos Walters, MBBS
- Section of Cardiac Electrophysiology and Arrhythmias, Division of Cardiology, University of California, San Francisco, California
- ↵∗Address for correspondence:
Dr. Edward P. Gerstenfeld, Section of Cardiac Electrophysiology and Arrhythmias, Division of Cardiology, University of California, San Francisco, 500 Parnassus Avenue, MUE RM433 East Tower, San Francisco, California 94143-1354.
- implantable cardioverter-defibrillators
- noninvasive programmed stimulation
- ventricular tachycardia
Implantable cardioverter-defibrillators (ICDs) can reduce the risk of sudden death in patients with structural heart disease and reduced ejection fraction. However, an ICD can only treat ventricular arrhythmias after they occur, resulting in painful shocks. Options for preventing recurrent ventricular arrhythmias generally include antiarrhythmic therapy or catheter ablation. Whereas earlier catheter ablation for ventricular tachycardia (VT) is now advocated by the recent European Society of Cardiology (ESC) guidelines (1), many cardiologists without access to advanced VT ablation centers will initially treat recurrent VT medically, and typically with amiodarone. The advantage of amiodarone is its long half-life, its established safety for outpatient initiation and maintenance, and its efficacy in treating ventricular arrhythmias. However, the side effects are well known and numerous. Whereas pulmonary toxicity is the most lethal and feared side effect, it is extremely rare with the lower doses used in contemporary VT management. Other side effects including hypothyroidisim or hyperthyroidisim, hepatotoxicity, peripheral neuropathy, visual changes, photosensitivity, poor appetite, and malaise are more commonplace. In previous studies randomizing patients to amiodarone use to suppress VT (EMIAT [European Myocardial Infarct Amiodarone Trial] (2), CAMIAT [Canadian Amiodarone Myocardial Infarction Arrhythmia Trial] (3)), the discontinuation rate of amiodarone due to side effects or adverse events ranged from 36.4% to 38.5%.
In the recently published VANISH (Ventricular Tachycardia Ablation or Escalated Drug Therapy) study (4), amiodarone and catheter ablation had similar efficacy in preventing recurrent VT in amiodarone naïve patients. Many centers without ready access to VT ablation will treat recurrent VT with amiodarone, and then only consider catheter ablation when VT recurs. Such patients are often transferred to high volume centers for ablation and then returned to the primary cardiologist for ongoing management. Antiarrhythmic drug management after ablation is often left to the referring cardiologist and patient, where the path of least resistance is often continuing amiodarone, particularly in patients who have experienced painful ICD shocks and may be reticent to have suppressive therapy stopped.
In this issue of JACC: Clinical Electrophysiology, Liang et al. (5) perform a retrospective analysis of patients referred for VT ablation at a single experienced center. They divide patients into 3 groups: those on amiodarone who had the dose reduced or discontinued after ablation (n = 99), those who had the drug continued or increased after ablation (n = 29), and those referred off amiodarone (n = 103). Patients who were continued on amiodarone were older, with lower left ventricular ejection fraction, were more frequently taking diuretics, and were more likely to already have a biventricular ICD at the time of ablation. One year after ablation, there was no difference in survival free from VT among the groups. In a multivariate analysis, older age, not performing programmed stimulation at the end of ablation, not performing noninvasive programmed stimulation, inducibility of clinical VT at noninvasive programmed stimulation, and higher amiodarone dose at discharge remained independently associated with shorter time to death. The investigators conclude that higher discharge amiodarone dose was associated with increased mortality in long-term follow-up, and that reduction or discontinuation of amiodarone should be considered a goal of VT ablation in patients with structural heart disease.
Can we conclude from this report by Liang et al. (5) that continued amiodarone use after VT ablation is a cause of increased mortality in these patients when compared with those who had amiodarone stopped? Clearly this association is confounded by the knowledge that at an experienced high volume center where amiodarone use is discouraged, only those patients with continued inducible VT or tenuous health were likely continued on amiodarone. This is reflected in the investigators’ findings that such patients were older, had lower ejection fraction, and more congestive heart failure than patients who had amiodarone discontinued. Lack of performing programmed stimulation after ablation also implies a group of patients who were felt to be too sick to undergo VT induction, and therefore an association with increased mortality is not surprising. The investigators used multivariable analysis to try and correct for these baseline differences among groups when examining the mortality outcome, but there likely remain numerous unmeasured confounders that render adjustment incomplete. The possibility that amiodarone use is fundamentally a marker of higher risk patients with more advanced structural heart disease is also supported by previous prospective randomized trials (2,3) finding that amiodarone, when specifically used to treat ventricular arrhythmias, has a neutral effect on mortality.
The more reassuring finding is that those patients who had amiodarone reduced or stopped after ablation did not have a higher VT recurrence rate than the groups who had amiodarone continued, and perhaps more importantly did not have a higher recurrence rate than the younger and healthier group in whom amiodarone was never started or was previously discontinued due to intolerance. This is an important point worth emphasizing. As electrophysiologists, it is incumbent on us to manage ventricular arrhythmia patients with the minimal dose of amiodarone required to maintain freedom from arrhythmias before, during, and after ablation. This includes attempts to decrease or discontinue amiodarone after successful ablation, as measured by lack of any VT inducibility, and as stated in the consensus guidelines. It is understandable that some patients may be reluctant to eliminate amiodarone after receiving multiple ICD shocks, however, most are willing to consider it after a period of arrhythmia quiescence. Clear communication with the referring cardiologist to reduce or eliminate amiodarone if no arrhythmias occur after 3 to 6 months can minimize long-term side effects. Recurrent arrhythmias can often be treated with less toxic medications or repeat ablation. Ongoing management by an electrophysiologist for all ventricular arrhythmia patients can help ensure that the appropriate dose of antiarrhythmics and proper monitoring for side effects of amiodarone are maintained (6). Liang et al. (5) should be congratulated for their findings that amiodarone can often be reduced or discontinued after successful ablation without leading to an increase in VT recurrence. This should serve to remind us that minimizing, or ideally eliminating, long-term amiodarone use is an important goal for our managing our patients with ventricular arrhythmias.
↵∗ Editorials published in JACC: Clinical Electrophysiology reflect the views of the authors and do not necessarily represent the views of JACC: Clinical Electrophysiology or the American College of Cardiology.
Dr. Gerstenfeld has received research grants and honoraria from Biosense-Webster and St. Jude Medical; and honoraria from Medtronic and Boston Scientific. Dr. Walters has reported that he has no relationships relevant to the contents of this paper to disclose.
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