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Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Instituto de Salud Carlos III Background The use of irreversible electroporation (IRE) as a method for cardiac ablation in the treatment of cardiac arrhythmias, known as Pulsed Field Ablation (PFA), has rapidly moved from preclinical studies to clinic. The reference indicator of acute lesion formation during cardiac ablation with thermal techniques consists in recording the local electrical activity changes. In the case of PFA, modifications in the electrical activity have been observed in areas that are not permanently damaged (reversible electroporation) but this is still poorly characterized. Of particular interest from a clinical perspective is to determine how and when the electrical activity of the reversible electroporation areas recovers after PFA. Purpose The purpose of this work was to simultaneously characterize the dynamic evolution of local electrograms after PFA in areas exposed to different levels of tissue damage. Methods High-density local unipolar electrograms were acquired at baseline, and continuously and during 60 min after each PFA application. The measurements were performed in different points of the right and left ventricular epicardial surface of 5 swine weighing 57±8 kg using an open-chest approach following the Principles of laboratory animal care" (NIH Publication no. 85-23 revised 1985). Under general anesthesia, a median sternotomy was made to create a surgical window. Unipolar electrograms were recorded using a 128-channel electrode matrix attached to the epicardial surface. For PFA ablation, a standard 8F, 3.5 mm tip monopolar catheter was positioned in the region corresponding to the center of the electrode array and a return electrode patch was attached to the back of the animals (see Fig. 1). At least 3 hours after the last ablation point, animals were euthanized and tissue was processed and stained with Triphenyltetrazolium Chloride (TTC) to assess acute lesion morphology. Results Our results show an immediate change in the morphology of unipolar electrograms: from basal biphasic electrograms to monophasic electrograms displaying a sudden ST-segment elevation (from 0.0±0.3 mV to 5.9±1.7mv; p Conclusions Our observations confirmed that the electrical activity of the reversible electroporation area was also acutely modified while the recovery dynamics were different from the irreversible damaged areas. Our preliminary analysis suggests that the different recovery dynamics observed could help in differentiating between reversible and irreversible electroporation areas.

Background The diagnosis of atrial infarction is often masked by the frequent association with ventricular infarction. For this reason, the electrophysiological and structural consequences of selective atrial ischemia are poorly understood. Purpose The objective of this study was to analyze the alterations in the ECG, local electrograms, and multifrequential atrial myocardial impedance in a new experimental model of acute and chronic atrial infarction. Methods Seven anesthetized pigs were subjected to 4h of atrial ischemia induced by selective catheter occlusion of the atrial coronary branches originating in the left circumflex coronary artery. The surface ECG was recorded and the changes in P-wave morphology analyzed. Four weeks later the animals were subjected to endocardial voltage mapping (Carto) and multifrequential impedance. The hearts were processed for anatomopathological study. Results Selective occlusion of the coronary atrial branches induced atrial infarction with fibrosis in the left atrium in 6 of the 7 cases (Figure). The surface ECG showed prolongation of the P-wave duration (Figure) (P-wave in lead II: from 72±8ms at baseline vs. 97±18ms at 4 weeks, ANOVA p Conclusion We developed a closed-chest swine model of selective atrial infarction suitable for the study of ECG patterns and electrophysiological mechanisms linked to atrial myocardial ischemia and infarction. The structural derangements are detectable by endocardial mapping of local voltage electrograms and local tissue impedance. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Supported by grants from ISCI-MINECO (FIS PI17/00069), FEDER, CIBERCV (CB16/11/00276)

Background Assessment of lesion formation remains one of the most important goals to guide radiofrequency (RF) procedures in the cardiac electrophysiology laboratory. Cardiac navigation systems use specific algorithms to predict the effective lesion size, but these metrics are based only on ablation parameters and ignore local electric tissue characteristics. [1] Recent studies show that local multiparametric impedance is influenced by the intrinsic structural characteristics of the tissue. [2] Purpose This study aimed to assess the ability of local multiparametric impedance to characterize acute and chronic RF ablation lesions in the right atrium of pigs. Methods Four anesthetized closed-chest pigs were submitted to two interventions. The first intervention aimed at creating RF ablation lesions (30W, 60s, 55°) in the right atrium using an electrocatheter connected to a conventional cardiac navigation system, while mapping the local multiparametric impedance (LMI), the generator impedance (GI) and the bipolar voltage (BiV). All RF ablation lesions were performed with a stable contact force. Four weeks later, the second intervention aimed at mapping again the previous ablation sites. After the second intervention animals were euthanized and the hearts were removed and processed to identify the presence of fibrosis in the previously ablated lesions (Figure). Results We performed 19 ablations (5±2 per animal) with an average contact force of 14.2±4.6g. Four weeks later, 14/19 (74%) ablation lesions were identified as fibrotic points in the explanted heart (Figure 1). These showed decreased acute LMI and BiV values that persisted low after 4 weeks (Table 1). The remaining 5/19 ablations that did not present fibrosis had lower baseline LMI and bipolar values that resulted in lower LMI and BiV drops (Table 1). The absolute drop in LMI between effective and non-effective lesions was around 50%, while GI drop was only 21% (LMI drop @51KHz: From −3.0±1.4° to −1.5±0.3°, T-TEST p Conclusion The local baseline electrical properties of atrial myocardium are directly related to the effectiveness of RF ablation lesions. RF ablation sites that resulted into persistent fibrosis points had larger LMI and BiV values, with higher absolute drops than non-effective lesions. The use of LMI in clinical practice could improve the outcome of the procedures of arrhythmia ablation in the electrophysiology lab. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Supported by grants from ISCI-MINECO (FIS PI21/00392), FEDER, CIBERCV (CB16/11/00276)

Trabajo presentado en el European Society of Cardiology Congress, celebrado en Barcelona (España), del 26 al 29 de agosto de 2022, Background: The phosphodiesterase-1C (PDE1C) and the adenosine A2A receptor (A2AR) are located in a macromolecular cluster and expected to modulate cAMP-dependent regulation of the intracellular calcium homeostasis in cardiac myocytes. In this contect, atrial fibrillation has been associated with a high incidence of spontanoeus arrhythmogenic calcium waves caused by excessive A2AR activation. On the other hand, inhibition of PDE1C and A2AR activation has also been reported to produce a synergistic and protective effect on cardiomyocyte survival, but little is known about the corresponding effects on the intracellular calcium homeostasis. Purpose: This study, therfore, aimed to investigate how PDE1 inhibition and/or A2AR activation modulate sarcoplasmic reticulum (SR) calcium homeostasis in mouse ventricular myocytes. Methods: Mouse ventricular myocytes (47 cells from 20 mice) were loaded with the calcium indicator Rhod-2 and spontaneous calcium release events at rest or caffeine induced calcium transients were visualized using resonance-scanning confocal microscopy at a frame rate of 150 Hz. The SR calcium content was estimated as the ratio of the peak fluorescence and the fluoresence the end of a 10 mM caffeine pulse (20s). Calcium leak was estimated as ratio of the flourescence emmision at baseline before and at the end of the caffeine pulse. Results: The incidence of spontaneous calcium waves or transients increased from 0.7±0.3 events/min in control to 1.1±0.5 events/min and 3.4±1.0 events/min (p

Background Atrial myocardial infarction may be a risk for atrial fibrillation. However, the electrophysiological and structural characteristics of the infarcted atrial myocardium are not well known. This study aimed to analyse the changes in local atrial electrograms and myocardial structure in an experimental model of isolated atrial myocardial infarction. Methods Five anesthetized, open-chest pigs were submitted to 4 hours of acute atrial myocardial ischemia induced by direct surgical clamping of atrial coronary branches originating from the right coronary artery. In all cases, we recorded simultaneously the 12-lead surface electrocardiogram (ECG) and the epicardial mapping of local atrial electrograms (17 x 12.5 mm patches containing 128 electrodes, with 1 mm inter-electrode distance) in a region close to the occluded branches and in control non-treated atria. The changes in local atrial QRS-ST segment and the amplitude of the P-wave of the ECG were sequentially analysed (Figure). The hearts were removed and processed for anatomopathological examination. Results Selective atrial coronary branch occlusion induced a patchy atrial myocardial necrosis with an irregular and abrupt border zone (circled areas in the Figure). During the first 15 min of ischemia, the local atrial electrograms showed increasing R waves, widening of QRS complex, and ST segment elevation leading to monophasic potentials (maximal ST segment at 30 min: from 0.2±0.7 mV to 1.9±1.4 mV, ANOVA p Structural and electrical atrial changes Conclusion Selective occlusion of atrial coronary branches induced patchy atrial myocardial necrosis with abrupt anatomical and electrical border zone. The overt QRS and ST segment changes in local atrial electrograms resembled those described in acute ventricular myocardial ischemia, and were associated with widening of the P-wave on the surface ECG. Although acute ischemic arrhythmias were not observed, the atrial structural alterations might set the substrate for re-entrant arrhythmias late after the healing over process. Acknowledgement/Funding Supported by grants from ISCI-MINECO (FISPI17/00069), CIBERCV (CB16/11/00276), FEDER and Fundaciό “La Maratό” TV3 (20150830).