Background Frailty is an aging-associated vulnerability to poor health comes when challenged by physiologic stressors. Frailty is a common problem amongst the elderly and is associated with increased mortality and health care resource utilization. Frailty is common in recipients of cardiac devices. What is not known is whether interventions will improve frailty and if this changes patient outcomes. Methods There are four chapters in this thesis. In chapter 1, a review of the current state of frailty research, methods of measurement, biomarkers, imaging modalities and interventions are presented. In chapter 2, a pilot randomized controlled trial is proposed to determine if a supervised exercise program and nutritional supplement improves physical frailty in cardiac device patients. Chapter 3 presents the results of the pilot study to date. In chapter 4, we discuss the challenges faced during the COVID-19 pandemic with respect to recruitment and conducting the trial and changes to the protocol that could have improved the study and adapted to the current state of research. Results There are two conceptual models of frailty which include the frailty phenotype and frailty index. Frailty instruments are abundant and there is no gold standard measurement. Frailty biomarkers, imaging techniques in their current state are complementary measures and are not yet ready for clinical practice. The DEFINIT P trial is single centre RCT involving 24 cardiac device patients randomized to 12 month supervised exercise program and nutritional supplement. Recruitment was halted due to COVID-19 pandemic. Conclusions Frailty is common in cardiac device recipients. A gold standard frailty instrument is not yet established though efforts are currently underway. The DEFINIT P study is feasible with respect to recruitment and consent targets but whether the adherence target to the exercise intervention and nutritional supplement is achieved remains unknown due to stopping the pilot trial as a result of the COVID 19 pandemic. / Thesis / Master of Science (MSc) / Frailty is a state of vulnerability in elderly that makes them susceptible to large declines in health from minor illnesses. Frail elderly are more likely to be admitted to the hospital, nursing homes and have higher chance of dying. Old age and frailty are not the same. Frailty is common in patients with a pacemakers and defibrillators. The purpose of this study is to test whether a supervised exercise program and a nutritional supplement will help improve frailty. We planned to recruit 24 patients into the randomized control trial and 100 patients in the registry and follow them for a period of one year. We aimed to understand how common is frailty in elderly with pacemakers and defibrillators and what factors contribute to developing frailty.

Nearly five million Americans are living with heart failure and 550,000 new cases are diagnosed each year in the US. Amongst the new approaches to develop a better solution for Congestive Heart Failure, Ventricular Recovery (VR) holds the most promise. A team, under the guidance of Dr. Criscione in the Cardiac Mechanics Lab at Texas A&M University, is currently developing an investigative device which aims to assist in VR by restoration of physiological strain patterns in the myocardial cells. The contribution of this thesis has been towards the development of a molding apparatus that yields a polymeric membrane whose shape, when inflated, is similar to the shape of the human heart. This membrane would surround the epicardial surface of the heart, when used for the device being discussed and in particular for the prototypes being developed. Contribution also includes a testing apparatus that measures the inflation of a membrane and simulation to predict the behavior of isotropic ellipsoids upon inflation. After unsuccessful implementations of two processing techniques, the successful design, fabrication implementation and attachment method meets the design criteria and is based on a thermoforming technique. Inflation profiles for membranes developed using this technique were studied at different pressures, with the axis length as variable. At 1kpa, which is the normal coronary arterial pressure, the membrane with an axis length of 140mm was found to show a shape which is similar to the shape of the human heart. In order to better understand and predict the shape an isotropic ellipsoidal membrane would take upon inflation without experimentation, simulations were carried out. Successful conversion of ellipsoidal geometry, with a few degrees of freedom as parameters, aided in simulation.

Cardiovascular disease is one of the most prevalent causes of death which has a high mortality rate. If identified early and treated appropriately, the mortality in patients with cardiovascular disease can be hugely reduced. For several decades, 12-Lead ECG has been the standard technique used to identify ischemia, and recent studies have shown that intracardiac electrogram has many benefits over external monitoring such as holter. ST Monitoring feature has been added to St. Jude Medical intracardiac cardioverter defibrillators (ICD) to leverage the ECG technology for identifying cardiovascular disease. This algorithm monitors the intracardiac electrogram to detect and report patterns which could be related to ischemic events. This feature is expected to enhance the process of identifying ischemia and infarction, and provides long-term management of the disease. In order to support the new implantable devices with ST Monitoring capability, the programmer software was updated to support this new feature in the device. This thesis discusses the work on the programmer. Chapter 1 begins with a background of how monitoring technology in an implantable device can benefit the patients facing high risk of myocardial infarction. Chapter 2 states the objective for the work on the programmer. Chapter 3 describes the implementation and the application of this feature. Conclusion and future development are discussed in Chapter 5.

Merlin.net Patient Care Network is a St. Jude Medical product that is used for remote patient management. The basic concept of Merlin.net is to allow the physician to view patient device follow-up information as well as general patient and device information on a web application. The Merlin.net system also interfaces with the patient and will send them notification if they miss a follow-up. All device information will be collected automatically while the patient is sleeping. This information is sent through a telephone line to a Merlin.net server to process a report package and display the collected information on the Merlin.net web application. The Merlin.net verification team ensures that all reports generated by the Merlin.net servers are processed and outputted correctly. There are currently 296 device parameters supported by Merlin.net, and the manual extraction and comparison of the expected parameter values takes several hours for each patient follow-up session. Currently there are 250 patient follow-up sessions used for verification testing. Each new release will continue to create additional patient follow-up sessions. Merlin.net releases are approximately 6 months apart, and each new release adds approximately 30-50 new patient follow-up records to support the new devices. In order to meet aggressive project deadlines, while ensuring that the Merlin.net system is processing and outputting patient follow-up data correctly, it is necessary to come up with an automated process to verify the contents of the processed data is correct. This will save a tremendous amount of time as well as improve on the quality of the verification process by eliminating human error and rework. It is critical for patient safety that the patient device follow-up information is processed and outputted correctly. In this thesis an automated process was developed to verify the correct content of the Merlin.net server generated reports for each patient follow-up session. This process leveraged different tools and scripting languages to achieve automation. TDE (Test Development Environment) tool was used to extract the device parameters from the patient follow-up sessions. The TDE script was written to extracts the desired parameter values from the patient follow-up session and automatically populates parameters in a device parameters spreadsheet. Once all the device parameter values are extracted in the spreadsheet, they are passed through a set of mapping rules, which form the expected values. The mapping rules were implemented as VBA (Visual Basic for Application) macros, one macro for each report. The VBA macros write the expected values back to the spreadsheet to form an “expected values spreadsheet”. The patient follow-up session is then sent to the Merlin.net server to process, which generates a processed patient follow-up session that contains a reports package in .zip format. A perl script was then written to compare the parameter values in the Merlinet.net generated reports with the corresponding expected values from the expected values spreadsheet. The perl script generates a comparison report displaying the discrepancies between the actual and the expected values.