Exploring Catheter Ablation and Drug Therapy Strategies in Post-Myocardial Infarction (MI) Ventricular Tachyarrhythmias: MANTRA-VT Trial

Ventricular tachyarrhythmias (VT/VF) in Post-Myocardial Infarction: Clinical Challenges

Ventricular tachyarrhythmias (VT/VF) are frequent in patients with prior myocardial infarction (MI). Although implantable cardioverter-defibrillators (ICDs) remain central to preventing sudden cardiac death, they are palliative and do not prevent recurrent arrhythmias; 10–50% of the ICD recipients have adequate ICD shocks within 3 years from the device implantation. Antiarrhythmic drugs, particularly amiodarone, have long been used to reduce VT/VF recurrences, but toxicity and drug interactions limit sustained therapy. Radiofrequency catheter ablation (RFCA) has emerged as an important alternative, yet the optimal timing for its use in post-MI patients continues to be debated.

Study Overview

The MANTRA-VT trial was designed to determine whether early substrate-based RFCA is superior to amiodarone therapy in reducing VT/VF burden among antiarrhythmic drug-naïve post-MI patients who had already experienced at least two VT/VF episodes documented by ECG or the device.

The trial was an investigator-initiated, multicentre, randomized, open-labelled, prospective trial. The trial randomly assigned 58 AAD naïve post-MI patients with an ICD and at least one documented VT/VF episode after device implantation to an initial treatment strategy.

Patients were randomized 1:1 to early substrate-based RFCA (n=28) or antiarrhythmic drug (AAD) therapy (n=30). RFCA targeted fragmented signals, late potentials, and inducible VTs within low-voltage regions. In the AAD arm, amiodarone was first-line (28 patients), with sotalol used in two patients due to contraindications. The primary endpoint was the cumulative number of VT/VF episodes ≥30 seconds over 12 months. Secondary endpoints included all-cause mortality, hospitalization, adverse events, and VT/VF burden at 24 months. All analyses followed an intention-to-treat approach.

Key Findings

The trial demonstrated that, at 12 months, the median number of VT/VF episodes (VT/VF burden) was zero in both the RFCA and the AAD group (P = 0.454). However, the distribution of episodes was highly skewed, and several patients experienced multiple episodes.

Crucially, the rates of device intervention differed significantly (figure 1):

• The rate of appropriate ICD shocks at 12 months was 7% in the RFCA group compared to 30% in the AAD group (P = 0.026).

• At 24 months, 82% of RFCA patients had no ICD therapies [including antitachycardia pacing (ATP) or shocks], compared to 63% in the AAD group (P = 0.012).

• ATP therapies at 24 months had occurred in 11% of RFCA patients versus 33% of AAD patients (P = 0.039).

Figure 1: Patients with VT/VF during a 12- and 24-month follow-up. AAD, antiarrhythmic drug therapy; ATP, antitachycardia pacing; ICD, implantable cardioverter defibrillator; RFCA, radiofrequency catheter ablation.

Regarding safety outcomes, there was no statistically significant difference between the groups in total mortality or hospitalization at 24 months. Non-fatal adverse events (AEs) were reported in 25% and 23% of the patients in the RFCA and the AAD group, respectively. Therapy-related AEs were reported in 3.6% of RFCA patients compared to 16.7% of AAD patients.

Clinical Message for Electrophysiologists

Although the median VT/VF burden was zero in both groups, the finding that early substrate-based RFCA was associated with a reduced risk of ICD therapies is clinically important. ICD shocks are painful and have been associated with increased mortality, reduced quality of life, and heart failure hospitalization. Given the strong association between ICD discharges and poor outcomes, the result that RFCA patients were more often free of ICD shocks than AAD patients is imperative.

In summary, early substrate-based RFCA achieved a significantly lower rate of required ICD therapies without compromising safety outcomes like mortality or hospitalization. This evidence supports consideration of implementing catheter ablation as the initial strategy for managing ventricular tachyarrhythmias in patients with ischaemic cardiomyopathy.

Reference: Pekka Raatikainen, Heikki Mäkynen, Juha Hartikainen, Mats Jensen Urstad, Leena Konkola, Niels C F Sandgaard, Peter Lukac, Arne Johannessen, Anders Jönsson, Peter Schuster, Carina Blomström-Lundqvist, Jussi Kuutti, Piia Lavikainen, Hannu Parikka, ; on behalf of the MANTRA-VT Investigators, Early substrate-based catheter ablation vs. antiarrhythmic drug therapy for ventricular tachyarrhythmias among patients with prior myocardial infarction: the MANTRA-VT randomized trial, EP Europace, Volume 27, Issue 10, October 2025, euaf236, https://doi.org/10.1093/europace/euaf236

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