Lb-456640-2 multicenter first in human clinical feasibility study to evaluate safety and efficacy of low energy multi-pulse therapy for ventricular tachycardia

Implantable cardioverter defibrillators (ICD) are effective in terminating ventricular tachycardia (VT). High energy shocks are deleterious and anti-tachycardia pacing is limited in suppressing VT. Multi-Pulse Therapy (MPT) is a novel anti-arrhythmic therapy which has a unique waveform sequence including multiple stages of electrical pulses, requires less energy compared to conventional biphasic defibrillation. Our study was a prospective non-randomized, non-blinded single-arm feasibility study to evaluate MPT among subjects who were considered for planned VT ablation, ICD implantation or generator revision. Patients scheduled for a procedure underwent placement of one ICD lead in right ventricle and a second ICD lead, decapolar electrophysiology catheter or permanent coronary sinus (CS) lead in a CS branch. All acute procedures were performed through femoral vein approach. The leads were externally connected to Cardialen External Stimulation System (CESS) to deliver MPT. After induction of sustained monomorphic VT, MPT was delivered with back up rescue external defibrillation if needed. Out of 29 patients screened, 6 patients were excluded for clinical reasons and the remaining 23 subjects were enrolled at 6 sites. Three subjects were excluded due to VT non-inducibility; therefore, 20 patients were included for analysis. The mean age was 69.6 ± 5.4 years and 100% were male. The majority of patients had ischemic cardiomyopathy (78.3%) and 82.6% presented with monomorphic VT. Out of 102 inductions, 82 VTs were induced and 148 MPTs were delivered. MPT terminated induced VTs in 70% of subjects, with 53.7% of total VT episodes converted. 90.9% of successfully converted VTs were hemodynamically stable. A higher VT conversion rate was observed with pacing electrodes used in CS (67.4%) as opposed to defibrillation coils in CS (36.1%). The success of VT conversion demonstrated a trend towards higher success with higher voltages. The success rate was 48.1% with ≤ 10V (average energy/per successful MPT was 0.015J) and 53.7% with ≤ 40 V (average energy/per successful MPT was 0.092J). Accelerations were seen in 11/148 (7.4%) sequences, similar to those reported in ATP literature (3.5-21%). MPT appears to be safe and feasible treatment strategy for VT patients which could be incorporated into ICDs. Randomized trials comparing to conventional therapy may provide more insight into independent or additive benefits of MPT treatment strategy Tabled 1MultiPulse Therapy by Electrophysiologic Parameters (LB-456640-2)Voltage(%)Total MPT Delivered≤ 10 V≤ 20 V≤ 40 V53.7(44/82)48.1(26/54)48.5(33/68)53.7(44/82)Electrode TypeTotal MPT DeliveredMPT SuccessMPT FailureMPT Efficacy (%)Defibrillation Coil36132336.1Electrophysiology Diagnostic Catheter *43291467.4Left Ventricular Quadripolar Lead32166.7VT Rate (bpm)≤ 188 bpm44281663.6>188 bpm35152042.9* Decapolar Catheter Abbreviations: MPT: MultiPulse Therapy; V: Volts Open table in a new tab * Decapolar Catheter Abbreviations: MPT: MultiPulse Therapy; V: Volts