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Lecture Notes in Bioengineering Tomasz Jadczyk Guido Caluori Axel Loewe Krzysztof S. Golba Editors Innovative Treatment Strategies for Clinical Electrophysiology Lecture Notes in Bioengineering Advisory Editors Nigel H. Lovell, Graduate School of Biomedical Engineering, University of New South Wales, Kensington, NSW, Australia Luca Oneto, DIBRIS, Università di Genova, Genova, Italy Stefano Piotto, Department of Pharmacy, University of Salerno, Fisciano, Italy Federico Rossi, Department of Earth, University of Salerno, Fisciano, Siena, Italy Alexei V. Samsonovich, Krasnow Institute for Advanced Study, George Mason University, Fairfax, VA, USA Fabio Babiloni, Department of Molecular Medicine, University of Rome Sapienza, Rome, Italy Adam Liwo, Faculty of Chemistry, University of Gdansk, Gdansk, Poland Ratko Magjarevic, Faculty of Electrical Engineering and Computing, University of Zagreb, Zagreb, Croatia Lecture Notes in Bioengineering (LNBE) publishes the latest developments in bioengineering. It covers a wide range of topics, including (but not limited to): • Bio-inspired Technology & Biomimetics • Biosensors • Bionanomaterials • Biomedical Instrumentation • Biological Signal Processing • Medical Robotics and Assistive Technology • Computational Medicine, Computational Pharmacology and Computational Biology • Personalized Medicine • Data Analysis in Bioengineering • Neuroengineering • Bioengineering Ethics Original research reported in proceedings and edited books are at the core of LNBE. Monographs presenting cutting-edge findings, new perspectives on classical fields or reviewing the state-of-the art in a certain subfield of bioengineering may exceptionally be considered for publication. Alternatively, they may be redirected to more specific book series. The series’ target audience includes advanced level students, researchers, and industry professionals working at the forefront of their fields. Indexed by SCOPUS, INSPEC, zbMATH, SCImago. · · · Tomasz Jadczyk Guido Caluori Axel Loewe Krzysztof S. Golba Editors Innovative Treatment Strategies for Clinical Electrophysiology Editors Tomasz Jadczyk Guido Caluori Department of Cardiology CRCTB—Inserm U1045 and Structural Heart Diseases IHU Liryc Medical University of Silesia Pessac, France Katowice, Poland Krzysztof S. Golba Axel Loewe Department of Electrocardiology Institute of Biomedical Engineering and Heart Failure Karlsruhe Institute of Technology (KIT) Medical University of Silesia Karlsruhe, Germany Katowice, Poland ISSN 2195-271X ISSN 2195-2728 (electronic) Lecture Notes in Bioengineering ISBN 978-981-19-6648-4 ISBN 978-981-19-6649-1 (eBook) https://doi.org/10.1007/978-981-19-6649-1 © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2022 This work is subject to copyright. All rights are solely and exclusively licensed by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. 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The registered company address is: 152 Beach Road, #21-01/04 Gateway East, Singapore 189721, Singapore Contents Stereotactic Radioablation for Treatment of Ventricular Tachycardia ....................................................... 1 Tomasz Jadczyk, Marcin Miszczyk, Radoslaw Kurzelowski, Tomasz Latusek, Jacek Bednarek, Krzysztof S. Golba, Jaroslaw Stachura, Zdenek Starek, Krystian Wita, and Slawomir Blamek Pulsed Field Ablation for the Interventional Treatment of Cardiac Arrhythmias ...................................................... 29 Guido Caluori, Annabelle Collin, Clair Poignard, and Pierre Jais High-Power Short-Duration Radiofrequency Ablation of Atrial Fibrillation ....................................................... 49 Adam Wojtaszczyk, Krzysztof Kaczmarek, and Paweł Ptaszyn´ski The Evolving Role of the Cardiac Conduction System in Cardiac Resynchronisation Therapy and Cardiac Pacing ...................... 61 Rafał Gardas, Danuta Łoboda, and Krzysztof S. Gołba Cardiac Contractility Modulation as a Novel Therapy for Patients with Heart Failure ................................................. 81 Dariusz Jagielski Machine Learning for Clinical Electrophysiology ..................... 93 Axel Loewe, Giorgio Luongo, and Jorge Sánchez Cardiac Digital Twin Modeling ..................................... 111 Axel Loewe, Patricia Martínez Díaz, Claudia Nagel, and Jorge Sánchez v Stereotactic Radioablation for Treatment of Ventricular Tachycardia Tomasz Jadczyk, Marcin Miszczyk, Radoslaw Kurzelowski, Tomasz Latusek, Jacek Bednarek, Krzysztof S. Golba, Jaroslaw Stachura, Zdenek Starek, Krystian Wita, and Slawomir Blamek Abstract Stereotactic arrhythmia radioablation (STAR) is an emerging treatment strategy for patients with intractable ventricular tachycardia refractory to antiarrhythmic medications and conventional radiofrequency catheter ablation. The electrophysiology-guided cardiac radioablation approach was introduced into clinical practice 10 years ago steadily gaining global interest. Subsequently, a substantial number of case reports and case series were published with several prospective trials established. This chapter will cover basic principles of STAR radiobiology, results of pre-clinical and clinical studies, the procedural STAR workflow and ongoing clinical trials. B T. Jadczyk ( ) · R. Kurzelowski Department of Cardiology and Structural Heart Diseases, Medical University of Silesia, 40-055 Katowice, Poland e-mail: [email protected] T. Jadczyk · Z. Starek Interventional Cardiac Electrophysiology Group, International Clinical Research Centre, St. Anne’s University Hospital Brno, 656 91 Brno, Czech Republic M. Miszczyk IIIrd Department of Radiotherapy and Chemotherapy, Maria Sklodowska-Curie National Research Institute of Oncology, 44-102 Gliwice, Poland T. Latusek · S. Blamek Department of Radiotherapy, Maria Sklodowska-Curie National Research Institute of Oncology, 44-102 Gliwice, Poland J. Bednarek Department of Electrocardiology, John Paul II Hospital, 31-202 Cracow, Poland J. Bednarek · K. S. Golba Department of Electrocardiology, Upper-Silesian Heart Center, 40-055 Katowice, Poland Department of Electrocardiology and Heart Failure, Medical University of Silesia, 40-055 Katowice, Poland J. Stachura American Heart of Poland, 47-200 Kedzierzyn-Kozle, Poland © The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2022 1 T. Jadczyk et al. (eds.), Innovative Treatment Strategies for Clinical Electrophysiology, Lecture Notes in Bioengineering, https://doi.org/10.1007/978-981-19-6649-1_1 2 T.Jadczyketal. 1 Introduction Globally, life-threatening ventricular arrhythmias, including ventricular tachycardia (VT) and ventricular fibrillation (VF), are associated with significant mortality and morbidity accounting for more than 4 million deaths every year (Tang et al. 2017; McDonagh et al. 2021). Despite multi-directional approaches, current treat ment strategies have considerable limitations while the effectiveness of antiarrhythmic drugs (AADs) may be hindered by toxicities. Furthermore, although implantable cardioverter-defibrillators (ICDs) prevent sudden cardiac death in patients at high risk of VT/VF (Al-Khatib et al. 2005; Bardy et al. 2005), the recurrent ICD interven- tions reduce quality of life and increase overall mortality in patients with heart failure (HF) (Larsen et al. 2011; Francis et al. 2006;Marketal.2 008). Despite its ability to precisely localise subendocardial arrhythmogenic substrates, treatment success of traditional invasive radiofrequency ablation (RFA) procedures are still suboptimal as almost 50% of all patients who underwent first-time RFA experience VT recurrence (Li et al. 2016). Accordingly, RFA of ventricular arrhythmias is technically challenging and highly operator-dependent because of anatomical factors and limited possibility to create transmural lesions (Kumar et al. 2016; Dinov et al. 2014; Tokuda et al. 2013). Furthermore, the success rate of catheter ablation is most favourable in patients with preserved left ventricular ejection fraction, ischemic aetiology and focal scar localised in subendocardial regions (Priori et al. 2015). On the contrary, individuals with impaired left ventricle contractility, diffuse scar or subepicardial localization of arrhythmogenic substrate as well as patients with prior unsuccessful RFA have worse outcomes (Kumar et al. 2016; Dinov et al. 2014; Tokuda et al. 2013). Of note, the traditional transcatheter ablation approach is associated with a risk of periprocedural cardiac perforation and tamponade with considerable short- term mortality rate of ≈5% in ischaemic cardiomyopathy VT cases (Santangeli et al. 2017). To overcome challenges of the RFA approach and deliver novel treatment strategies for refractory VTs, experimental non-invasive stereotactic radioablation (STAR) demonstrated favourable clinical potential, being implemented in several centres worldwide as a second line option, especially in situations where conventional RFA has failed or was contraindicated (Cuculich et al. 2017; Loo et al. 2015; Robinson et al. 2019a). Thus, STAR opens a new window of opportunity for patients with intractable VTs leveraging established strategies routinely used for treatment of malignancies. STAR comprises of various combinations of pre-treatment medical Z. Starek 1st Department of Internal Medicine-Cardioangiology, St. Anne’s University Hospital Brno, 656 91 Brno, Czech Republic 1st Department of Internal Medicine-Cardioangiology, Faculty of Medicine, Masaryk University, 656 91 Brno, Czech Republic K. Wita First Department of Cardiology, Medical University of Silesia, 40-055 Katowice, Poland StereotacticRadioablationforTreatmentofVentricularTachycardia 3 imaging and/or electroanatomical mapping (EAM), followed by computed tomog- raphy (CT)-guided high-precision delivery of a large radiation dose to the region of arrhythmia substrate. Minimizing access site complication issues and procedural risks, high-energy X-rays delivered in a single-fraction are considered ablative by triggering fibrotic response over weeks and months (Refaat et al. 2017; Lehmann et al. 2016; Rapp et al. 2019). However, novel studies indicate that the effect of STAR could take place through radiation-mediated reprogramming of cardiac conduction by Notch signalling increasing conduction velocity and subsequently preventing occurrence of electrical reentry for VT (Zhang et al. 2021). From the procedural standpoint, STAR requires a multidisciplinary approach combining electrophysiology, radio-oncology and interventional cardiology to perform diagnostic evalu- ation, substrate localization, treatment planning and the irradiation procedure. To enable more precise target delineation, multimodal co-registration of EAM and cCT is essential. Thus, software-based integrative approaches have been developed to integrate these two imaging modalities (Hohmann et al. 2020). This chapter will present basic principles of STAR radiobiology, pre-clinical and clinical studies, procedural workflow for preparation of STAR treatment and ongoing clinical trials. 2 Mechanisms of Scar-Related Ventricular Tachycardia and Radiofrequency Catheter Ablation Treatment The most challenging ventricular arrhythmias are often scar-related VTs concomitant with congenital heart diseases, which are associated with a significant risk of sudden cardiac death. The principal mechanism of the arrhythmia relies on the electrical reentry loop within the scar and scar-border zone. Inside the fibrotic scar, there are electrophysiologically functional myocytes which form isthmi with entrance and exit, inner loops, outer loops and bystanders. (Fig. 1) These structures present heterogenous conduction velocity and altered refractoriness, which construct the substrate for reentry. In the anatomical sense, the impulse can propagate from the vital tissue through the entrance of the isthmus and protected area of slow conduction within the dense scar. The main aim of ablation is to block the critical isthmi and the exit sites, as well as to eliminate potential ectopic triggers. The electrophysiological features during sinus rhythm which predict the site of VT origin are low-amplitude, prolonged, multicom- ponent, endocardial and diastolic potentials. It is possible to perform further diag- nostics with a Three Dimensional (3D) EAM system using entrainment mapping for hemodynamically stable VT, substrate mapping for unstable VT and for localisation of the triggers. The results of these three techniques can ideally indicate the ablation targets localising critical isthmi, exit sites, slow conducting areas and triggers for VT. 4 T.Jadczyketal. Bystander Bystander Fig. 1 Graphical presentation of heterogenous myocardial scar structure The ablation of VT is performed with endo- and/or epicardial access using RF application carried out as a point or a linear lesion. The traditional targets are the critical isthmus within the scar, exit sites and ectopic origins of ventricular extrasystolic beats. Another therapeutic strategy is based on the “scar homogenisation” technique, which is an effective way of eliminating all substrates within the scar. Preferably, the successful end-point confirmed by substrate mapping is non-inducibility of VT, elimination of channels and lack of abnormal intracardiac electrocardiograms. Note- worthy, the termination of arrhythmia upon RFA application is a very promising endpoint, however, it does not indicate the definite elimination of the VT circuit (Fig. 2). The acute ablation success rate reaches 67–96%. However, even a combination of entrainment and substrate mapping is associated with the risk recurrence up to 30–46% in long-term follow-up, despite repeated ablations and optimal medical treatment (Callans et al. 2001). The non-optimal efficacy of endocardial VT ablation can be associated with the limited size and depth of the RFA lesion. Furthermore, patients with scar-related VT and impaired contractility can develop new VT circuits despite previous ablations. The complication rate of scar-related VT ablation is about 14% (death 2.7%, other major complications 5.3%, minor complications 6%) (Calkins et al. 2000). Importantly, even in the case of initially effective VT ablation (elimination of all existing arrhythmia substrates and non-inducibility of tachycardia), patients with impaired left ventricular contractility require ICD implantation due to the risk of sudden cardiac death (McDonagh et al. 2021).