1. Intracardiac electrogram analysis may allow for prediction of lesion transmurality after pulsed field ablation of atria in a porcine modelJernej Štublar, Tomaž Jarm, Lars M. Mattison, Bryan D. Martin, Megan M. Schmidt, Matevž Jan, Atul Verma, Paul A. Iaizzo, Daniel C. Sigg, Damijan Miklavčič, 2025, izvirni znanstveni članek Povzetek: Background Pulsed field ablation (PFA) is a novel cardiac ablation modality with an increasing clinical acceptance in treatment of atrial fibrillation due to its clinical efficacy and excellent safety profile. However, intraprocedural guidance for PFA to ensure durable pulmonary vein isolation (PVI) is lacking. Objective We quantified changes in intracardiac electrograms (iEGMs) following PFA and radiofrequency ablation (RFA) and investigated their applicability for prediction of lesion transmurality. Methods We induced 38 atrial lesions using PFA or RFA in 5 swine and monitored iEGMs continuously for up to 30 minutes postablation. The most characteristic changes in iEGMs were quantified after the decomposition using discrete wavelet transform, which allowed us to analyze the effects in separate frequency bandwidths. Results After the ablation, we observed a reduction of bipolar iEGM amplitude (for PFA and RFA) and an increase in unipolar iEGM amplitude (predominantly for PFA). These changes were due to 2 mechanisms with different frequency content. The low-frequency content of unipolar iEGMs (1–16 Hz) further enabled us to discriminate between transmural and nontransmural lesions in the case of PFA. The rate of reduction of initially increased current-of-injury effect reflected in the low-frequency content of unipolar iEGMs within the first few minutes postablation was significantly higher and more pronounced for nontransmural lesions. Conclusion This study shows that unipolar iEGMs can be used to differentiate between transmural and nontransmural atrial lesions within minutes after PFA in a porcine model, with implications for development of intraprocedural guidance of PFA procedures. Ključne besede: pulsed field ablation, atria porcine model, intracardiac electrograms, bipolar vs unipolar iEGM, frequency analysis, discrete wavelet transform, current of injury, lesion transmurality Objavljeno v DiRROS: 14.04.2026; Ogledov: 151; Prenosov: 98
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2. Modulation of contactless high intensity pulsed electromagnetic field induced electroporation and gene delivery efficacy using various nanoparticlesTamara Polajžer, Matej Krajnc, Slavko Kralj, Maja Caf, Rok Romih, Samo Hudoklin, Vitalij Novickij, Damijan Miklavčič, 2026, izvirni znanstveni članek Povzetek: Introduction: High-intensity pulsed electromagnetic fields (HI-PEMF) can be used to trigger contactless permeabilization of the plasma membrane similar to electroporation (EP). The permeabilization efficiency and gene delivery by HI-PEMF in vitro are currently inferior to EP. It was suggested that the methodology can be improved with conductive gold nanoparticles (AuNPs), which are reported to amplify the induced electric field in close proximity to the cell membrane. Objectives: Therefore, in this work, we have studied different NPs, which varied in material/conductivity (gold and silica), size (10–50+ nm), shape (i.e., round and rods), concentration (50–200 µg/mL), and functionalization (pegylated or not), and combined them with HI-PEMF (6.7 T × 100 pulses, 1 Hz). Methods: The normal Chinese hamster ovary cell line (CHO) and the cancer human urinary bladder’s transitional carcinoma cell line (T24) were used as a model. We have characterized cell membrane permeabilization using propidium iodide (PI) and the efficacy of gene delivery using pEGFP-N1. Results: Larger NPs and higher NP concentrations resulted in up to a 10% increase in membrane permeability. In contrast, semispherical and rod-shaped AuNPs did not further enhance permeabilization efficiency. Gene delivery efficiency increased from 3% in control samples to 6% in the presence of 50 nm AuNPs. Overall, CHO cells were more susceptible to HI-PEMF-induced effects than T24 cells. Conclusions: This study shows the potential to increase gene delivery efficacy by combining HI-PEMF treatment with conductive NPs. However, it was concluded that the HI-PEMF-induced effects are highly dependent on the cell line, NP type, and concentration and therefore require further investigation. Ključne besede: gene delivery Objavljeno v DiRROS: 24.02.2026; Ogledov: 320; Prenosov: 201
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3. Modified unipolar return pulsed field ablation in ventricular myocardiumMaria Terricabras Casas, Peter Lombergar, Terenz Escartin, Bor Kos, Philippa R. Krahn, Jennifer Barry, Graham Wright, Tomaž Jarm, Jernej Štublar, Matej Kranjc, Nicolas Coulombe, Lars M. Mattison, Daniel C. Sigg, Damijan Miklavčič, Atul Verma, 2025, izvirni znanstveni članek Povzetek: BACKGROUND: Various pulsed field ablation (PFA) parameters have been proposed to improve lesion depth. This study evaluated a modified unipolar return PFA system to create deep lesions in healthy and infarcted ventricular myocardia. METHODS: Numerical modeling was used to compare a modified unipolar return PFA system configuration with a conventional unipolar return (skin patch). We then performed ablation in 14 swine (5 with chronic myocardial infarction and 9 healthy). PFA lesions were created in the left ventricle using a focal catheter (4-mm tip) with a return electrode positioned in the inferior vena cava (biphasic, microsecond pulses of 1300 and 1500 V, 1–16 trains). Electroanatomical mapping guided ablation and lesion localization on magnetic resonance imaging were performed 48 hours post-ablation in the infarcted group and at 1 day, 7 days, and 6 weeks post-ablation in the healthy group. RESULTS: Numerical modeling demonstrated that the modified unipolar return PFA system produced deeper lesions with reduced variability compared with the skin patch. In healthy pigs (n=35 lesions), depths of 6.8±1.8 mm and widths of 11.5±4.7 mm were achieved with 8 pulse trains. Depths of 8.2±2.8 mm and widths of 14.0±4.7 mm were achieved with 16 trains. The maximum lesion depths were 8.8 and 11.6 mm for 8 and 16 trains, respectively. In the infarcted cohort (n=22 lesions), all lesions applied to scar tissue penetrated through fibrotic regions, with epicardial involvement observed in 57% of lesions. CONCLUSIONS: The modified unipolar return PFA system effectively creates large lesions and can achieve transmurality in healthy and infarcted animals. Compared with conventional unipolar, it may offer greater lesion depth, width, and consistency. GRAPHIC ABSTRACT: A graphic abstract is available for this article. Ključne besede: atrial fibrillation, catheter ablation, heart ventricles, pulmonary veins, tachycardia ventricular Objavljeno v DiRROS: 11.12.2025; Ogledov: 331; Prenosov: 234
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4. Llimited efficacy of nanoparticle-assisted electroporation for membrane permeabilization and gene electrotransferTamara Polajžer, Matej Kranjc, Slavko Kralj, Maja Caf, Rok Romih, Samo Hudoklin, Federica Rocca, Damijan Miklavčič, 2025, izvirni znanstveni članek Povzetek: Nanoparticles (NPs) were previously explored as enhancers in electroporation due to their potential to locally amplify electric fields near cell mem branes, with gold nanoparticles (AuNPs) in particular showing promise in improving membrane permeability and gene electrotransfer (GET). In this study, we systematically investigated the influence of NP properties—including size, shape, surface functionaliza tion, and material—on electroporation efficacy. Methods: A combined approach using theoretical modeling and experimental validation was employed, encompassing numerical simulations, membrane permeabilization assays, transmission electron microscopy Numerical results revealed that the presence of NPs alters local electric field distributions, but the amplification is highly localized, regardless of NPconductivity or geometry. Experimentally, only two out of six tested NP types produced a statistically significant, yet modest, increase in membrane permeability at one electric f ield intensity. Similarly, GET improvement was observed with only one NP type, with no dependence on concentration or functionalization. Conclusions: Overall, our findings demonstrate that NPs, under tested conditions, do not substantially enhance cell membrane permeability or GET efficacy. These conclusions are supported by both computational modeling and in vitro experiments Ključne besede: nanodelci, numerični model, elektro tansfer Objavljeno v DiRROS: 02.12.2025; Ogledov: 986; Prenosov: 189
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5. Elucidating the mechanisms of microbubble formation in intracardiac pulsed field ablationSamo Mahnič-Kalamiza, Damijan Miklavčič, Peter Lombergar, Blaž Mikuž, Lars M. Mattison, Daniel C. Sigg, Bor Kos, 2024, izvirni znanstveni članek Povzetek: Delivery of electrical energy for sensing or therapeutic purposes often involves electrochemical phenomena at the electrode-electrolyte solution interface. Release of gaseous bubbles that accompanies delivery of pulsed electric fields to tissues in applications such as electrochemotherapy of tumours and irreversible electroporation or pulsed field ablation in cardiac electrophysiology needs to be understood and characterized. We present an in vitro study using pulsed field delivery into saline, employing multiple different treatment protocols, two electrode geometries (pair of needles and a modified RF catheter), and two imaging systems to elucidate the complex relationship between the electrical treatment protocol, temperature changes at and around the electrodes, and gas release due to pulse delivery. Our primary objective was to identify the key parameters responsible for bubble formation and to highlight the importance of the treatment parameters and their interplay – ranging from the temperature to appropriate choice of electrode geometry, and, most importantly, to the choice of the treatment protocol. We found that bubbles originating from electrochemical reactions are more prevalent in monophasic pulsing protocols, whereas in high frequency biphasic pulsing protocols the bubbles are mainly caused by boiling of the medium. Degassing of liquid due to lower solubility of gasses at elevated temperatures does seems to play a role, though a minor one. We also observed that bubbles caused by boiling collapse very rapidly, whereas electrochemically produced bubbles or those produced through degassing appear to have longer lifetimes. Therefore, the treatment protocols most suited to minimizing gas release are biphasic trains of short (▫$\mu$▫s) pulses with a significant inter-pulse delay (i.e. low duty cycle) to prevent excessive heating. Moreover, electrodes must be designed to avoid high local current densities. Our findings have broad implications extending from lab-on-achip cell electroporation devices to intracorporeal pulsed field applications in the cardiovascular system, particularly pulsed field ablation procedures. Ključne besede: pulsed field ablation, gas release, electrochemistry, Joule heating, water phase transition Objavljeno v DiRROS: 10.04.2025; Ogledov: 869; Prenosov: 528
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6. Nanosecond electric pulses are equally effective in electrochemotherapy with cisplatin as microsecond pulsesAngelika Vižintin, Stefan Marković, Janez Ščančar, Jerneja Kladnik, Iztok Turel, Damijan Miklavčič, 2022, izvirni znanstveni članek Ključne besede: electroporation, electrochemotherapy, nanosecond pulses, cisplatin Objavljeno v DiRROS: 25.07.2024; Ogledov: 1043; Prenosov: 731
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8. Percutaneous image guided electrochemotherapy of hepatocellular carcinoma : technological advancementMihajlo Djokić, Rok Dežman, Maja Čemažar, Miha Štabuc, Miha Petrič, Lojze Šmid, Rado Janša, Boštjan Plešnik, Maša Omerzel, Urša Lampreht Tratar, Blaž Trotovšek, Bor Kos, Damijan Miklavčič, Gregor Serša, Peter Popović, 2020, izvirni znanstveni članek Povzetek: Background. Electrochemotherapy is an effective treatment of colorectal liver metastases and hepatocellular carcinoma (HCC) during open surgery. The minimally invasive percutaneous approach of electrochemotherapy has already been performed but not on HCC. The aim of this study was to demonstrate the feasibility, safety and effectiveness of electrochemotherapy with percutaneous approach on HCC. Patient and methods. The patient had undergone the transarterial chemoembolization and microwave ablation of multifocal HCC in segments III, V and VI. In follow-up a new lesion was identified in segment III, and recognized by multidisciplinary team to be suitable for minimally invasive percutaneous electrochemotherapy. The treatment was performed with long needle electrodes inserted by the aid of image guidance. Results. The insertion of electrodes was feasible, and the treatment proved safe and effective, as demonstrated by control magnetic resonance imaging. Conclusions. Minimally invasive, image guided percutaneous electrochemotherapy is feasible, safe and effective in treatment of HCC. Ključne besede: electrochemotherapy, hepatocellular carcinoma, percutaneous, minimally invasive Objavljeno v DiRROS: 12.07.2024; Ogledov: 1266; Prenosov: 526
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9. The use of high-frequency short bipolar pulses in cisplatin electrochemotherapy in vitroMaria Scuderi, Matej Reberšek, Damijan Miklavčič, Janja Dermol-Černe, 2019, izvirni znanstveni članek Ključne besede: electroporation, electrochemotherapy, high-frequency bipolar pulses, cisplatin, cell survival, drug uptake Objavljeno v DiRROS: 09.07.2024; Ogledov: 1196; Prenosov: 679
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10. Radiological findings of porcine liver after electrochemotherapy with bleomycinMaja Brložnik, Nina Boc, Gregor Serša, Jan Žmuc, Gorana Gašljević, Alenka Seliškar, Rok Dežman, Ibrahim Edhemović, Nina Milevoj, Tanja Plavec, Vladimira Erjavec, Darja Pavlin, Maša Omerzel, Erik Brecelj, Urša Lampreht Tratar, Bor Kos, Jani Izlakar, Marina Štukelj, Damijan Miklavčič, Maja Čemažar, 2019, izvirni znanstveni članek Objavljeno v DiRROS: 05.07.2024; Ogledov: 1280; Prenosov: 694
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