A Predictive and an Optimization Mathematical Model for Device Design in Cardiac Pulsed Field Ablation Using Design of Experiments.

Cardiac catheter ablation (CCA) is a common method used to correct cardiac arrhythmia. Pulsed Field Ablation (PFA) is a recently-adapted CCA technology whose ablation is dependent on electrode and waveform parameters (factors). In this work, the use of the Design of Experiments (DoE) methodology is investigated for the design and optimization of a PFA device. The effects of the four factors (input voltage, electrode spacing, electrode width, and on-time) and their interactions are analyzed. An empirical model is formed to predict and optimize the ablation size responses. Based on the ranges tested, the significant factors were the input voltage, the electrode spacing, and the on time, which is in line with the literature. Two-factor interactions were found to be significant and need to be considered in the model. The resulting empirical model was found to predict ablation sizes with less than 2.1% error in the measured area and was used for optimization. The findings and the strong predictive model developed highlight that the DoE approach can be used to help determine PFA device design, to optimize for certain ablation zone sizes, and to help inform device design to tackle specific cardiac arrhythmias.

Optimizing Cardiac Wireless Implant Communication: A Feasibility Study on Selecting the Frequency and Matching Medium.

Cardiac wireless implantable medical devices (CWIMD) have brought a paradigm shift in monitoring and treating various cardiac conditions, including heart failure, arrhythmias, and hypertension. One of the key elements in CWIMD is the implant antenna which uses radio frequency (RF) technology to wirelessly communicate and transmit data to external devices. However, wireless communication with a deeply implanted antenna using RF can be challenging due to the significant loss of electromagnetic (EM) signal at the air-skin interface, and second, due to the propagation and reflection of EM waves from different tissue boundaries. The air-skin interface loss of the EM wave is pronounced due to the absence of a matching medium. This paper investigates the EM propagation losses in the human body and presents a choice of optimal frequency for the design of the cardiac implant antenna and the dielectric properties of the matching medium. First, the dielectric properties of all tissues present in the human thorax including skin, fat, muscle, cartilage, and heart are analyzed as a function of frequency to study the EM wave absorption at different frequencies. Second, the penetration of EM waves inside the biological tissues is analyzed as a function of frequency. Third, a transmission line (TL) formalism approach is adopted to examine the optimal frequency band for designing a cardiac implant antenna and the matching medium for the air-skin interface. Finally, experimental validation is performed at two ISM frequencies, 433 MHz and 915 MHz, selected from the optimal frequency band (0.4-1.5 GHz) suggested by our analytical investigation. For experimental validation, two off-the-shelf flexible dipole antennas operating at selected ISM frequencies were used. The numerical and experimental findings suggested that for the specific application of a cardiac implant with a penetration depth of 7-17 cm, the most effective frequency range for operation is within 0.4-1.5 GHz. The findings based on the dielectric properties of thorax tissues, the penetration depth of EM waves, and the optimal frequency band have provided valuable information on developing and optimizing CWIMDs for cardiac care applications.

Electroporation Parameters for Human Cardiomyocyte Ablation In Vitro.

Cardiac ablation with irreversible electroporation (IRE) is quickly being established as a modality of choice for atrial fibrillation treatment. While it has not yet been optimised, IRE has the potential to significantly limit collateral damage and improve cell-specific targeting associated with other energy sources. However, more tissue and cell-specific evidence is required to demonstrate the selective threshold parameters for human cells. The aim here is to determine the optimal ablation threshold parameters related to lesion size for human cardiomyocytes in 2D culture. Conventional biphasic pulses of different field strengths and on-times were delivered in a monolayer culture system of human AC16 cardiomyocytes. The dynamics of cell death and lesion dimensions were examined at different time points. Human cardiomyocytes are susceptible to significant electroporation and cell death at a field strength of 750 V/cm or higher with 100 µs pulses. Increasing the IRE on-time from 3 ms to 60 ms reduces the effective field threshold to 250 V/cm. Using very short pulses of 2 µs and 5 µs also causes significant cell death, but only at fields higher than 1000 V/cm. A longer on-time results in more cell death and induced greater lesion area in 2D models. In addition, different forms of cell death are predicted based on the evolution of cell death over time. This study presents important findings on the ability of different IRE parameters to induce human cardiomyocyte cell death. Lesion size can be tuned by appropriate choice of IRE parameters and cardiomyocytes display an upregulation of delayed cell death 24 h after electroporation, which is an important consideration for clinical practice.