Banca de DEFESA: JOSE CARLOS GOMES JUNIOR

Uma banca de DEFESA de MESTRADO foi cadastrada pelo programa.
DISCENTE : JOSE CARLOS GOMES JUNIOR
Data: 22/04/2026
HORA: 14:00
LOCAL: Sala 107 Bloco Zeta Campus São Bernardo do Campo
TÍTULO:

Electrophysiological characterization of the epicardium in the rabbit animal model through voltage mapping technique

PÁGINAS: 100
RESUMO:

Cardiovascular diseases remain the leading cause of death worldwide, with cardiac arrhythmias playing a central role in this scenario due to their high clinical impact, treatment costs, and, in some cases, lethality. Electroanatomic voltage mapping is an essential tool for the characterization and identification of arrhythmogenic substrates. However, the voltage cutoff values used in clinical practice remain largely empirical and vary according to the mapping system, acquisition configuration (unipolar and bipolar), and the cardiac chamber being analyzed. In this dissertation, the voltage mapping technique was applied to a rabbit animal model (New Zealand White breed) with the aim of performing electrophysiological characterization in isolated hearts perfused using the Langendorff system, as well as correlating these findings with structural alterations in cardiac tissue. Epicardial unipolar and bipolar electrograms from the right atrium (RA), left atrium (LA), and ventricular region (V) were acquired using multi-electrode arrays (MEAs) composed of electrodes made of different materials: silver (Ag), platinum/iridium (Pt/Ir), and platinum (Pt). The same analysis pipeline was applied to different cardiac rhythms (sinus rhythm (SR), bradycardia (B), atrial tachycardia (AT), ventricular tachycardia (VT), and ventricular fibrillation (VF)), aiming to preserve amplitude: signals were first preprocessed using a 60 Hz notch filter and a 0.5–250 Hz bandpass filter to remove baseline drift and high-frequency noise, followed by processing involving peak-to-peak amplitude calculation and statistical analyses. Data normality was assessed using the Shapiro–Wilk test in SR signals, followed by a comparative analysis between electrode materials using the nonparametric Kruskal–Wallis test (with Dunn’s post-hoc test). The same dataset (1600 activations per material and per chamber for unipolar, and 1000 for bipolar, in 15 s windows) was used to define voltage cutoff values for healthy epicardial tissue using the 95th percentile, resulting in threshold determination for Ag, Pt/Ir, and Pt materials in both unipolar and bipolar configurations for RA, LA, and V. The variability of peak-to-peak amplitudes among SR, B, AT, VT, and VF rhythms was assessed using the paired nonparametric Wilcoxon signed-rank test, comparing rhythms obtained in the same heart (analyses performed with unipolar electrograms, Pt electrodes, and 10 s windows), and correlating these findings with histological analyses of the studied hearts, evaluating five parameters: (1) expansion of the intercellular space, (2) degree of myofibrillar disorganization, (3) mononuclear cell infiltration, (4) presence of clustered nuclei, and (5) nuclear density. Finally, epicardial substrate characterization for AT and VF was performed using voltage maps and optical Local Activation Time (LAT) maps derived from panoramic optical mapping. The distribution of SR data (unipolar and bipolar), assessed by the Shapiro–Wilk test, showed a non-Gaussian distribution (p < 0.001) across all chambers and materials. Comparison among electrode materials demonstrated statistically significant differences in unipolar signal amplitudes in all cardiac chambers (RA: H = 2790.62; p < 0.001; ε² = 0.581), (LA: H = 2963.90; p < 0.001; ε² = 0.617), and (V: H = 1902.95; p < 0.001; ε² = 0.396). Median peak-to-peak amplitudes were 4.4 mV (RA), 4.8 mV (LA), and 17.1 mV (V) for Ag; approximately 7.4 mV (RA) and 5.7 mV (LA) for Pt/Ir; and 17.0 mV (RA), 22.6 mV (LA), and 34.9 mV (V) for Pt. Dunn’s post-hoc test confirmed significant differences between all material pairs (Ag × Pt/Ir, Ag × Pt, and Pt/Ir × Pt) with p < 0.001 for RA and LA. In the ventricle, the difference was significant between Ag and Pt (p < 0.001). These differences were reflected in voltage cutoff values: for Ag electrodes, unipolar thresholds were 2.6 mV (RA), 2.0 mV (LA), and 8.8 mV (V), and bipolar thresholds were 0.8 mV (RA), 0.9 mV (LA), and 4.1 mV (V). For Pt/Ir, unipolar thresholds were 3.8 mV (RA) and 3.3 mV (LA), and bipolar thresholds were 2.8 mV (RA) and 2.3 mV (LA). Pt electrodes showed the highest thresholds, with unipolar values of 7.4 mV (RA), 8.9 mV (LA), and 17.4 mV (V), and bipolar values of 4.1 mV (RA), 5.7 mV (LA), and 9.5 mV (V). Analysis of peak-to-peak amplitude variability across cardiac rhythms revealed significant changes. In B, there was a significant reduction in amplitudes in most chambers (14.3 → 2.5 mV; −83%; p < 0.0001), although increases were observed in some cases (6.5 → 10.5 mV; +62%; p = 0.017). In AT, amplitudes significantly decreased in most cases (28.2 → 9.9 mV; −65%; p < 0.0001), except in some chambers where the reduction was not significant (17.1 → 9.5 mV; −44%; p = 0.38). In VT, responses varied, including marked reductions (31.0 → 8.3 mV; −73%; p < 0.0001), slight increases (6.5 → 7.5 mV; +15%; p = 0.017), and non-significant reductions (23.6 → 15.7 mV; −33%; p = 0.16). In VF, highly significant amplitude reductions were observed in all cases (p < 0.0001), including one case with a 90% reduction (31.0 → 2.7 mV; −91%; p < 0.0001). Histological analysis of hearts corresponding to the studied rhythms showed alterations in all five evaluated parameters, whereas the control heart not perfused in the Langendorff system showed preserved tissue across all parameters. The perfused heart without arrhythmia induction or programmed stimulation showed a 20–30% reduction in amplitude distribution during the experiment, compared to 70–90% reductions observed in arrhythmic hearts. The integrated characterization of electrophysiological and histological data demonstrated that changes in electrogram amplitudes are associated with structural modifications of cardiac tissue, evidencing the presence of an electroanatomic substrate underlying arrhythmias. Additionally, amplitude variability across different rhythms does not depend exclusively on electrical dynamics but is also influenced by experimental factors such as perfusion time and programmed stimulation. The characterization of epicardial substrates of AT and VF using voltage maps and optical LAT maps demonstrated that voltage mapping in the animal model is capable of discriminating low-voltage areas associated with regions of complex LAT, successfully characterizing structural (VF) and functional (AT) arrhythmic mechanisms. Finally, for the first time, voltage thresholds for healthy epicardial tissue were established for the rabbit model, enabling further studies using voltage mapping techniques in animal models to improve electroanatomic mapping methodologies for characterizing arrhythmogenic mechanisms and their corresponding substrates, providing a robust platform with strong translational impact.

MEMBROS DA BANCA:
Presidente - Interno ao Programa - 2231661 - JOAO LOURES SALINET JUNIOR
Membro Titular - Examinador(a) Externo à Instituição - OMER BERENFELD
Membro Titular - Examinador(a) Externo à Instituição - ROSANA ALMADA BASSANI - UNICAMP
Membro Suplente - Examinador(a) Interno ao Programa - 1188948 - JOAO LAMEU DA SILVA JUNIOR
Membro Suplente - Examinador(a) Externo ao Programa - 1957691 - RONNY CALIXTO CARBONARI
Membro Suplente - Examinador(a) Externo à Instituição - MATHEUS CARDOSO MORAES - UNIFESP