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).