DISCUSSION
In patients with ICM, VT/VF is a major cause of morbidity and mortality. Thus, strategies to minimize arrhythmia burden in these patients is essential. Our study, which included 505 patients with a mean follow-up duration of 24 ± 9 months, showed that patients with ICM presenting with VT/VF, first-line catheter ablation have a significant lower rate of recurrent appropriate ICD therapies compared to patients receiving an initial approach based on medical therapy (RR 0.70, 95% CI 0.56-0.86). This was significantly important in the subgroup of patients with moderately depressed LVEF (>30-50%) (HR: 0.52, 95% CI: 0.36-0.76) compared to patients with severely depressed LVEF (</=30%), where no benefit was seen (HR: 0.56, 95% CI: 0.24-1.32).
In patients implanted with secondary prevention ICDs, shocks have been reported in up to ~39% of patients within the first year of implantation.3 Recurrent ICD shocks, may cause deterioration of heart failure, increase hospitalization rates, and have been associated with increased mortality.8 The SCD-HeFT trial noted that a single appropriate ICD shock increased patient mortality-risk up to five-fold.8 Shocks with their potential to worsen HF, also tend to alter mode of mortality in the direction of non-arrhythmic death, thereby, offsetting the arrhythmic mortality advantage offered by ICDs.9Moreover, they do not alter the underlying pathological substrate, and do not prevent VT. Therefore, it is important to adopt a strategy that reduces the absolute incidence of VT/VF, and as such, subsequent ICD shocks. Utilization of AADs and ICD reprogramming have been employed with moderate degrees of success.3 Accordingly, the VANISH trial demonstrated that there was a significantly lower rate of the composite primary outcome of death, VT storm, or appropriate ICD shock among patients undergoing catheter ablation than among those receiving an escalation in AAD (HR, 0.72; 95% CI, 0.53 to 0.98; p = 0.04).10
In patients with ICM, VT usually arises from a fairly distinct region of the myocardium, within or neighboring the scar tissue. This scar tissue is comprised of non-excitable fibrous material, with islands of surviving myocytes composing the substrate for VT. A general physiology seems to be common in patients with ICM and sustained monomorphic VT, characterized by larger endocardial lower voltage zones, more frequent fractionated, very late voltage potentials as compared to patients with a similar profile without VT.11 Nonetheless, scars are not homogenous considering tissue characteristics can be variable in each patient depending largely on the infarct type (i.e., size, location, revascularization time, etc.) posing a challenge for the treatment of VT/VF. Therefore, is not surprising that ablation studies have shown variable results reflecting conservative guideline recommendations. Guidelines recommend VT ablation as a Class I indication in patients with prior MI, only with recurrent episodes of symptomatic sustained VT, or VT storm, and have failed or are intolerant to AADs.2 However, this recommendation may not apply to every patient, as there seems to be a significant benefit in different subgroups of patients including those undergoing early ablation and preserved LVEF.12 In general, a lower threshold to consider catheter ablation of VT (whether it is determined by failure of 1 AAD or immediately after a VT episode) could be associated with a favorable outcome.12 Furthermore, data from the International VT Ablation Center Collaborative Group, reported higher rates of both VT recurrence and mortality in patients with lower EF and higher NYHA status.13 In contrast, ICM and higher EF (>30%) were associated with lower probability of VT recurrence that was reflected in improved transplant-free survival compared to those with VT recurrence (93% vs. 89%, adjusted HR 3.190 (1.517-6.707); p = 0.002).13
Four randomized controlled trials have assessed the impact of first-line VT catheter ablation in the setting of ICM.5,6,14,15SMASH VT and VTACH trials showed improved outcomes with first-line VT ablation in patients with ICM presenting with VT.5,6However, the SMS and the recently published BERLIN VT trial, showed opposite results.14,15 As expected, all of these trials had methodological differences but the major approach studied is homogenous, considering the use of first-line VT ablation in each of them and a medication-based approach in the control groups. In terms of the control groups, AADs were used in 35% of patients in the VTACH study, 32% in SMS, and 33% in BERLIN VT; however, only beta-blockers were used in SMASH VT.5,6,15,16 All control groups were medications based except in the BERLIN VT trial, where patients were randomized to receive ablation after the third appropriate ICD shock.15 Ultimately, 10 patients (12%) received ablation in this group, which is perhaps one of the reasons the trial showed no benefit in the ablation groupo.15 They showed that first-line VT ablation did not reduce the combined endpoint of mortality or hospitalization for arrhythmia or worsening heart failure during 1 year of follow-up when compared to the deferred ablation strategy (HR, 1.09; 95% CI, 0.62-1.92; P=0.77).15 Perhaps the study power, patient cross-over, and endocardial-only ablation strategy were not enough to demonstrate a significant clinical benefit of ablation. VT circuits in ICM are generally thought to have a subendocardial location, easily accessible, and targeted with endocardial mapping and ablation.17 However, 34-75% of ICM patients may exhibit epicardial substrate, as confirmed by magnetic resonance imaging in post-infarct animal models.18 This may explain why a combined endocardial-epicardial ablation have been shown to be beneficial in ICM. We recently published a meta-analysis with 17 studies including 975 patients.19 After a mean follow-up of 27 months, endocardial-epicardial ablation was associated with a 35% reduction in risk of VT recurrence compared with endocardial ablation alone (RR: 0.65; 95% CI: 0.55 to 0.78; p < 0.001). Sensitivity analysis showed lower risk of VT recurrence in ICM (RR: 0.43; 95% CI: 0.28 to 0.67; p= 0.0002) with a nonsignificant trend in NICM (RR: 0.87; 95% CI: 0.70 to 1.08; p = 0.20). More importantly, an endocardial-epicardial approach was associated with reduced all-cause mortality (RR: 0.56; 95% CI: 0.32 to 0.97; p = 0.04), particularly in patients with ICM.19 As such, perhaps early ablation using an endocardial-epicardial strategy in patients with LVEF >30-50% could be the most beneficial therapeutic strategy.
Despite the mixed results from the four RCTs evaluating this concept, our results substantiate the use of VT ablation as a first-line approach in this population to improve survival-free from VT/VF, which may also have a positive impact from a healthcare resource utilization standpoint. Winterfield et al .20, in a large-scale, real-world, retrospective analysis of 523 patients noted a decline in median cardiac rhythm-related medical expenditures of approximately $5,400 per patient-year ($7,318 pre-ablation to $1,910 post-ablation, p<0.0001). A significant reduction in all-cost total medical expenditure was noted in the subgroup of patients without repeat ablation (~37% reduction; p = 0.0005). The expenditures for device follow-ups were also noted to have a significant decline in this subgroup ($906 to $824, p = 0.05). Multiple clinical studies are currently underway aiming to address the best therapeutic approach of these patients: Does Timing of VT ablation Affect Prognosis in Patients with an ICD? (PARTITA) (NCT01547208); Pan-Asia United States PrEvention of Sudden Cardiac Death Catheter Ablation Trial (PAUSE-SCD) (NCT02848781); The Antiarrhythmics or Ablation for Ventricular Tachycardia 2 (VANISH 2) Study (NCT02830360).