Cardiac Ablation by Electroporation: Effects of Pulsed Field Ablation Field Strength and Repetition on Lesion Characteristics in the Atria and Ventricle

Atrial fibrillation (AF) is a common arrhythmia associated with a high morbidity and mortality rate. The incidence and prevalence of AF are increasing and reaching epidemic measures. Cardiac ablation and pulmonary vein isolation are effective methods of managing AF reducing the rate of AF hospitalization, and in specific populations, AF ablation reduces mortality and morbidity. Pulsed-field ablation (PFA) is an emerging and promising non-thermal technology for cardiac ablation. The effective applied voltage to achieve adequate irreversible myocardial injury is not well studied. The pulsed-field strength remains independent of tissue contact; therefore, PFA is assumed to be an ablation technology, not mandating the need for tissue contact. Chapter 2 evaluates the association between lesion depth created by PFA and contact, providing insight into the correlation between applied PFA voltages and the depth of irreversible myocardial injury. The catheter design and configuration determine the catheter contact. Inter-electrode spacing and the gaps between catheter splines affect the lesion size. Chapter 3 examines the association between catheter design and configuration on the lesion sets, providing a better understanding of the size and continuity of lesions created by basket, spiral, and adjustable circular catheters. The cell membrane generates a potential gradient. An abrupt increase in the cell membrane gradient can temporarily increase the membrane’s permeability (reversible electroporation). A significant increase in the cell membrane gradient by external sequential shock waves could disrupt the membrane leading to cellular apoptosis (irreversible electroporation). Chapter 4 investigates the acute effect of three doses of pulsed field ablation (PFA) when applied to the antrum of pulmonary veins. Electrical isolation of pulmonary veins immediately after application of low, intermediate, and high doses of PFA were examined. Additionally, the number of PFA applications to achieve pulmonary vein isolation was examined in this chapter. The procedural success in achieving pulmonary vein isolation was dose-dependent, and higher field strength of PFA resulted in a better acute pulmonary vein block. In this study, all three different doses of PFA were compared to conventional radiofrequency ablation. Reversible electroporation of the myocardial cells at the antrum of the pulmonary veins results in a temporary electrical block. However, the long-term success of ablation by pulmonary vein isolation is dependent on the durability of the electrical block induced by irreversible electroporation. Chapter 5 evaluates the effect of PFA dose and repetition on lesions' durability, providing valuable insight into the association between high doses of PFA and bonus ablations after the initial block in increasing durability. Although more repetitive PFA at higher doses results in durable lesions and better outcomes, the safety of high doses of PFA has not been well documented. Chapter 6 evaluates the safety of multiple applications of high doses of PFA. A comparison between three doses of PFA and conventional radiofrequency ablation revealed that PFA causes more significant myocardial injury; however, it is safe, resulting in no collateral damage. Finally, homogenising scar tissue could terminate ventricular tachycardia. Sometimes, endocardial ablation is inadequate, not resulting in a transmural lesion necessitating epicardial ablation. Epicardial ablation close to coronary arteries can cause extra myocardial injury by interrupting coronary artery flow. Therefore, delivering deep and transmural lesions by endocardial ablation without damaging coronary arteries is ideal for the ablation of ventricular tachycardia. Chapter 7 investigates the effect of different doses of PFA when delivered in a unipolar fashion on the depth and volume of ventricular lesions.Thesis (Ph.D.) -- University of Adelaide, Adelaide Medical School, 202