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Sammar Fathy Elhabal,1 Nashwa Abdelaal,2 Saeed Abdul Kareem Saeed Al-Zuhairy,3 Mohamed Fathi Mohamed Elrefai,4,5 Ahmed Mohsen Elsaid Hamdan,6 Mohamed Mansour Khalifa,7 Sandra Hababeh,8 Mohammad Ahmad Khasawneh,9 Gehad M Khamis,10 Jakline Nelson,11 Passant M Mohie,10 Rania A Gad,12 Amira Rizk,13 Soad L Kabil,14 Mohamed Kandeel El-Ashery,15,16 Bhaskara R Jasti,17 Nahla A Elzohairy,18,19 Tayseer Elnawawy,20 Fatma E Hassan,21,22 Mohamed A El- Nabarawi23 1Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Modern University for Technology and Information (MTI), Mokattam, Cairo, Egypt; 2Department of Integrative Physiology, Baylor College of Medicine, Houston, TX, USA; 3Department of Pharmacy, Kut University College, Kut, Wasit, Iraq; 4Department of Anatomy, Histology, Physiology and Biochemistry, Faculty of Medicine, The Hashemite University, Zarqa, Jordan; 5Department of Anatomy and Embryology, Faculty of Medicine, Ain Shams University, Cairo, Egypt; 6Department of Pharmacy Practice, Faculty of Pharmacy, University of Tabuk, Tabuk, Saudi Arabia; 7Department of Human Physiology, Faculty of Medicine, Cairo University, Cairo, Egypt; 8Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia; 9Department of Chemistry, College of Science U.A.E. University, Al-Ain, United Arab Emirates; 10Department of Clinical Pharmacology, Faculty of Medicine, Alexandria University, Alexandria, Egypt; 11Department of Microbiology and Immunology, Faculty of Pharmacy, Nahda University, Beni-Suef, Egypt; 12Department of Pharmacology and Toxicology, Faculty of Pharmacy, Nahda University, Beni-Suef, Egypt; 13Food Science and Technology Department, Faculty of Agricultural, Tanta University, Tanta, Egypt; 14Department of Clinical Pharmacology, Faculty of Medicine, Zagazig University, Zagazig, Egypt; 15Pharmaceutical Chemistry Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt; 16Medicinal Chemistry Department, Faculty of Pharmac

Sammar Fathy Elhabal,1 Nashwa Abdelaal,2 Saeed AS Al-Zuhairy,3 Mohamed Fathi Mohamed Elrefai,4,5 Mohamed Mansour Khalifa,6 Mohammad Ahmad Khasawneh,7 Ahmed Mohsen Elsaid Hamdan,8 Passant M Mohie,9 Rania A Gad,10 Soad L Kabil,11 Mohamed Kandeel El-Ashery,12,13 Bhaskara R Jasti,14 Nahla A Elzohairy,15,16 Nehal Elfar,17 Tayseer Elnawawy,18 Fatma E Hassan,19,20 Mohamed Ahmed El-Nabarawi21 1Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Modern University for Technology and Information (MTI), Mokattam, Cairo, Egypt; 2Department of Integrative Physiology, Baylor College of Medicine, Houston, TX, USA; 3Department of Pharmacy, Kut University College, Kut, Wasit, Iraq; 4Department of Anatomy, Histology, Physiology, and Biochemistry, Faculty of Medicine, The Hashemite University, Zarqa, Jordan; 5Department of Anatomy and Embryology, Faculty of Medicine, Ain Shams University, Cairo, Egypt; 6Department of Human Physiology, Faculty of Medicine, Cairo University, Cairo, Egypt; 7Department of Chemistry, College of Science, U.A.E. University, Al-Ain, United Arab Emirates; 8Department of Pharmacy Practice, Faculty of Pharmacy, University of Tabuk, Tabuk, Saudi Arabia; 9Department of Clinical Pharmacology, Faculty of Medicine, Alexandria University, Alexandria, Egypt; 10Department of Pharmacology and Toxicology, Faculty of Pharmacy, Nahda University, Beni-Suef, Egypt; 11Department of Clinical Pharmacology, Faculty of Medicine, Zagazig University, Zagazig, Egypt; 12Pharmaceutical Chemistry Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt; 13Medicinal Chemistry Department, Faculty of Pharmacy, King Salman International University, Ras-Sedr, South Sinai, Egypt; 14Department of Pharmaceutics and Medicinal Chemistry, Thomas J. Long School of Pharmacy & Health Sciences, University of the Pacific, Stockton, CA, USA; 15Air Force Specialized Hospital, Cairo, Egypt; 16Department of Microbiology and Immunology, Faculty of Pharmacy, Modern University

Sudden cardiac death (SCD) remains one of the leading causes of death in the modern world with most of these deaths being attributed to ventricular arrhythmias. Implantable cardiac defibrillators (ICDs) are well established treatment and are recommended by the international guidelines for prevention of sudden cardiac death triggered by ventricular arrhythmias in high-risk populations. But they are not risk-free, and traditional transvenous ICDs are associated with long-term complications with potentially fatal consequences. The subcutaneous ICD (S-ICD) was designed utilising a totally extra-thoracic approach avoiding the complications which have been associated with transvenous ICDs (TV-ICD). The results of clinical trials demonstrated the efficacy of the S-ICD systems in recognising and treating ventricular arrythmias with fewer lead-related complications when compared to the TV-ICDs. However, the downside of the S-ICDs is that unlike TV-ICDs, they are unable to provide bradycardia pacing or Anti-tachycardia pacing (ATP) therapy to terminate ventricular arrythmias painlessly without the need to deliver a shock. Also, they exhibit a relatively higher rate of inappropriate shocks when compared with TV-ICDs. Most of these shocks can be attributed to Twave oversensing (TWO), an inherent risk to the sensing mechanism of the S-ICD. Not all patients are eligible for S-ICDs and mandatory screening of all potential candidates following device manufacturer guidelines helps identify eligible patients based on their underlying ECG morphology. Variable rates of screening success and S-ICD eligibility are reported in the literature. In this thesis I will start by reporting a retrospective analysis of S-ICD eligibility using current recommended screening practices at a tertiary centre for cardiac devices (University Hospital of Southampton). I will then proceed to suggest adopting a different approach towards screening of S-ICD candidates which considers the dynamicity of the ECG

Subcutaneous Implantable Cardioverter-Defibrillators (S-ICDs) are used for prevention of sudden cardiac death triggered by ventricular arrhythmias. T Wave Over Sensing (TWOS) is an inherent risk with S-ICDs which can lead to inappropriate shocks. A major predictor of TWOS is a high T:R ratio (the ratio between the amplitudes of the T and R waves). Currently patients' Electrocardiograms (ECGs) are screened over 10 seconds to measure the T:R ratio, determining the patients' eligibility for S-ICD implantation. Due to temporal variations in the T:R ratio, 10 seconds is not long enough to reliably determine the normal values of a patient's T:R ratio. In this paper, we develop a convolutional neural network (CNN) based model utilising phase space reconstruction matrices to predict T:R ratios from 10-second ECG segments without explicitly locating the R or T waves, thus avoiding the issue of TWOS. This tool can be used to automatically screen patients over a much longer period and provide an in-depth description of the behaviour of the T:R ratio over that period. The tool can also enable much more reliable and descriptive screenings to better assess patients' eligibility for S-ICD implantation.