Corticosteroid Therapy After Catheter Ablation of Atrial Fibrillation for an Authentic “Blanking Period”

The Role of Inflammation in AF

A number of studies have indicated that inflammation might play a significant role in the initiation, maintenance, and perpetuation of AF and that C-reactive protein (CRP) is related to the mechanism responsible for the processes leading to AF (8–12). Local and systemic inflammation created by the myocardial damage resulting from radiofrequency burns seems to play a prominent role in patients undergoing ablation. Moreover, inflammatory processes may participate in the heterogeneity of the action potential duration of the atrial and/or pulmonary vein myocardium by chemical mediators and may ultimately result in the creation of arrhythmogenic substrate (13). A similar mechanism has been suggested to explain the atrial arrhythmias occurring early after cardiac surgery, acute myocardial infarction, or successful electrical cardioversion (11,14).

Corticosteroid Therapy in AF Prophylaxis

The widest experience with the effect of corticosteroid therapy on AF prophylaxis has been accumulating during the past 30 years in adult cardiac surgery patients. In a meta-analysis of 50 randomized controlled trials, Ho and Tan (14) showed that intravenous corticosteroid therapy before and/or after cardiopulmonary bypass was associated with a significant reduction in the risk of AF. In 1 study, glucocorticoid therapy significantly reduced the risk of recurrent and permanent AF in patients with AF that was not secondary to a precipitating condition (10). In contrast, in 2 large population-based, case-control studies, an increased risk of AF was found during current use (15) or a high-dose regimen (16) of oral corticosteroid therapy.

Corticosteroid Therapy After AF Ablation

In this issue of the Journal, Koyama et al. (17) reported the first study that evaluated the effects of corticosteroids on the rate of AF recurrence in patients who underwent pulmonary vein ablation for symptomatic paroxysmal AF. This prospective, double-blind, randomized study involved 125 patients (60 in the corticosteroid-treated group and 65 in the placebo group). Patients in the corticosteroid group were given intravenous hydrocortisone (2 mg/kg) immediately after the procedure followed by oral prednisolone (0.5 mg/kg/day) for 3 days after the procedure. All of the patients underwent clinical, electrocardiographic, and biological monitoring that included measurements of body temperature (BT) and high-sensitivity CRP levels during 3 consecutive days after the ablation procedure. After 1 week of hospitalization, all of the patients were regularly followed up with 24-h Holter electrocardiographic and portable electrocardiographic monitoring during a 14-month period. The arrhythmias observed during the first month after ablation were classified as immediate AF (during the first 3 days), early AF (between days 3 and 30), and no AF (no arrhythmia recurrence during the first 30 days).

The main results of the study were 3-fold. 1) Corticosteroid therapy led to a significant reduction in AF recurrence rate during the first month after ablation (27% and 49% in the treated and placebo groups, respectively). This was mainly achieved due to a marked reduction in immediate AF recurrence rate (7% and 31%, respectively), whereas the rate of early AF recurrence remained similar in both groups (20% and 18%, respectively). 2) Eighty-five percent of the corticosteroid group had no AF recurrences without any antiarrhythmic drugs 14 months after ablation compared with 71% in the placebo group (p < 0.05). 3) The maximal BT and CRP levels during the initial 3 days after ablation and the increase in BT and CRP levels between baseline and the 3-day time point were significantly lower in the corticosteroid group than in the placebo group. The authors also noted that there were no side effects that could be attributed to the treatment. In a previous study that the same investigators had conducted with a different and larger patient cohort (n = 186) (13), immediate AF recurrence was more closely associated with an acute inflammatory process (as attested by changes in BT and CRP levels) than early AF recurrence. In addition, after a 6-month follow-up, the AF-free rate was significantly greater in the immediate AF recurrence group (76%) than in the early AF recurrence group (30%).

The present study is well designed and provides the first objective evidence that the immediate atrial tachyarrhythmias occurring during the first 3 days after AF ablation are due to an inflammatory response that can be significantly decreased by a short course of corticosteroid therapy. The early arrhythmias occurring between days 3 and 30 were not, however, associated with an inflammatory response, thereby supporting the results of studies suggesting that such arrhythmias may be due to pulmonary vein–left atrium conduction recovery (18). Irrespective of the specific mechanism of action of corticosteroid therapy on the various arrhythmic periods after ablation, it is gratifying that this therapy resulted in a 50% reduction rate of AF events during the first month after AF ablation. Although the study by Koyama et al. (17) did not provide data on the consequences of AF recurrences for the patients in terms of need for antiarrhythmic medication adjustments, hospitalization, or electrical cardioversion, the decrease in the AF burden is very likely to improve the quality of life for some patients and possibly increase the cost-effectiveness of the procedure as well. As the authors stated, their finding of a small but significant lower recurrence rate of AF at the 14-month follow-up post-ablation is difficult to explain by the short course of corticosteroid therapy and warrants further confirmation.

Study Limitations

The study of Koyama et al. (17) has several limitations, some of which were acknowledged and addressed by the authors. 1) The population size of the study is relatively small. 2) The authors used CRP and BT as markers of inflammation of the ablated myocardium, but these markers lack specificity. 3) There is no information about the proportion of patients with diabetes mellitus, one of the most prominent conditions associated with AF (19). According to a recent report (20), this population should not be excluded from undergoing AF ablation. 4) The information on safety and tolerance of corticosteroid therapy is insufficient. No data were provided on blood glucose concentrations in the corticosteroid-treated group despite the fact that blood glucose levels are expected to increase in both nondiabetic and type 2 diabetes patients (14,21). 5) Finally, the authors did not discuss the possible deleterious effect of corticosteroid therapy on slowing the healing of the ablated tissues, an effect that could favor late cardiac perforations (22).

Clinical Implications

The significant reduction in the rate of post-ablation atrial tachyarrhythmias during the blanking period by means of a short course of corticosteroid therapy is interesting and may be clinically important. This finding should stimulate further studies on the long-term safety and the clinical and cost-effective benefits of this therapy. The question of whether the results of the present study should prompt us to include corticosteroid therapy in our routine practice or whether we should wait for confirming studies is difficult to answer. In any event, the authors should be congratulated for making a contribution that will undoubtedly encourage further work on these critical issues.