Ventricular tachycardia (VT): Mortality implications in patients with cardiomyopathy, impact of VT ablation and development of new invasive treatment strategies.

Abstract

Background Ventricular tachycardia (VT) is a common complication affecting patients with structural heart disease and poor left ventricular systolic function. Its occurrence is linked to increased mortality despite treatment with an implantable cardioverter defibrillator (ICD) and there are several challenges that are still to be solved. This thesis will focus on 4 unanswered aspects of the management of VT in a translational fashion, encompassing large registry data and cohort studies, development of new mapping tools in humans and validation of novel electrograms in a preclinical swine model. These advancements will add knowledge to the field of this complex and deadly arrhythmia. Hypotheses and Objectives: 1) To assess the prognostic impact of ICD therapies in secondary prevention patients suffering VT. 2) To quantify the healthcare usage of patients treated with catheter ablation for recurrent VT compared to medical management. 3) To establish a mechanistic VT ablation guided by decrement evoked potential (DEEP) mapping. 4) To prove that omnipolar EGMs used in vivo identify the substrate of VT accurately and without the directional influences that affect bipolar EGMs. Methodology: 1) Retrospective analysis of the Ontario ICD database and Cox-regression modeling to quantify independent risk factors for mortality in 7020 ICD recipients. 2) Propensity-matched analysis of catheter ablation versus medical management of 100 matched patients. 3) Multicenter prospective study of VT substrate mapping for the detection of DEEP regions in the VT substrate and its correlation to activation mapping and clinical outcomes. 4) Preclinical swine model of ventricular substrate to explore the utility of direction-independent omnipolar EGMs. Results: 1) Patients treated with secondary prevention ICDs are exposed to an increased mortality after experiencing a life-saving ICD intervention (Antitachycardia pacing, namely ATP or shocks). 2) Patients with symptomatic recurrent VT treated with VT ablation experience a similar healthcare consumption compared to patients treated medically. 3) A mechanistic substrate mapping and ablation strategy targeting DEEP is highly specific for the detection of the critical regions of the VT circuit without the need to induce it. 4) The use of orientation-independent Omnipolar EGMs provide a reliable and physiological way of mapping with higher peak to peak voltages compared to any bipolar EGMs. Conclusions The mortality impact of ICD interventions spans from primary to secondary prevention patients. Managing VT ablation invasively yields a decrease in VT burden with respect to the pre-ablation state without incurring in increased healthcare costs when compared to medical treatment. Mechanistic DEEP mapping is a useful tool to assess the VT substrate. Omnipolar EGMs provide a good physiological representation of the VT substrate in a preclinical swine model.