The cardiac nervous system consists of nested reflex feedback loops that interact to regulate regional heart function. Cardiac disease affects multiple components of the cardiac nervous system and the myocytes themselves. This study aims to determine: 1) how select components of the cardiac nervous system respond to acute cardiac stress, including myocardial ischemia (MI) and induced neural imbalance leading to cardiac electrical instability, and 2) how neuromodulation can affect neural-myocyte interactions to induce cardioprotection. Thoracic spinal cord stimulation (SCS) is recognized for its anti-anginal effects and ability to reduce apoptosis in response to acute MI, primarily via modulation of adrenergic efferent systems. The data presented here suggest that cervical SCS exerts similar cardioprotective effects in response to MI, but in contradistinction to thoracic SCS, uses both adrenergic and cholinergic efferent mechanisms to stabilize cardiomyocytes and the arrhythmogenic potential. SCS potentially can use efferent and/or anti-dromically activated cardiac afferents to mediate its cardioprotection. Thoracic SCS mitigates the MI-induced activation of both nodose and dorsal root ganglia cardiac-related afferents, doing so without antidromic activation of the primary cardiac afferents. Instead, thoracic SCS acts through altering the cardiac milieu thereby secondarily affecting the primary afferent sensory transduction. In response to cardiac stressors, reflex activation of efferent activity modifies mechanical and electrical functions of the heart. Excessive activation of neuronal input to the cardiac nervous system can induce arrhythmias. Stimulation of intrathoracic mediastinal nerves directly activates subpopulations of intrinsic cardiac neurons, thereby inducing atrial arrhythmias. Neuromodulation, either thoracic SCS or hexamethonium, suppressed mediastinal nerve stimulation (MSNS)-induced activation of intrinsic cardiac neurons and correspondingly reduced the arrhythmogenic potential. SCS exerted its stabilizing effects on neural processing and subsequent effects on atrial electrical function by selectively targeting local circuit neurons within the intrinsic cardiac nervous system. Together these data indicate that neuromodulation therapy, using SCS, can mitigate the imbalances in cardiac reflex control arising from acute cardiac stress and thereby has the potential to slow the progression of chronic heart disease.

No description available.

Stress cardiomyopathy can cause significant morbidity in the functional life of patients. The most common finding is apical ballooning of the left ventricle on cardiac catheterization. Some cases present with atypical imaging findings. This report presents a case of atypical stress cardiomyopathy with midventricular hypokinesis.

No description available.

Wearable technology offers the promise of decentralized and personalized healthcare, which can both alleviate current burdens on medical resources, and also help individuals to be more informed about their health. The heterogeneity of disease phenotypes necessitates adaptations to both diagnosing and surveilling disease, but to ensure user adoption and behavioral change, there needs to be a convenient way to amass such health information continuously. This can be in part accomplished by the development of continuously monitoring, compact wearable medical sensors and analytics technology that provide updates on analyte and biosignal measurements at regular intervals in situ. This dissertation investigates methods for collecting and analyzing information from wearable devices with these principles in mind. In Aim 1, we developed new methods for analysis of cardiovascular biosignals. Current methods of estimating left ventricular mass index (LVMI, a strong risk factor for cardiac outcomes), rely on the analysis of echocardiographic signals. Though still the gold standard, echocardiography can typically only be performed in the clinic, making it inconvenient to obtain frequent measurements of LVMI. Frequent measurements can be useful for monitoring cardiac risk, particularly for high-risk individuals, so we investigated the feasibility of predicting LVMI using a deep learning-based approach through ambulatory blood pressure readings, a one-time laboratory test and demographic information. We find that adding blood pressure waveform information in conjunction with multitask learning improved prediction errors (compared to baseline linear regression and neural network models), pointing to its potential as a clinical tool. Using transfer learning, we developed a model that does not require waveform data, but achieved similar prediction accuracies as methods that do require such data – opening the door to use cases that eliminate the need for wearing a blood pressure cuff continuously during the measurement period. Overall, such a technique has the potential to provide information to individuals who are at high risk of cardiac outcomes both inside and outside the clinic. In Aims 2 and 3, we developed a minimally invasive hydrogel patch for continuous monitoring of calcium, as proof-of-concept for wearable measurement of a wide variety of analytes typically assayed in the lab – a technology that can facilitate treatment and management of many prevalent diseases. Specifically, in Aim 2, we engineered a DNA polyacrylamide hydrogel microneedle array that sensed physiologically relevant calcium levels, for potential use by individuals who have hypoparathyroidism, a condition in which blood calcium levels are low and calcium supplements are needed. A negative mold was made using a CNC mill, the positive mold was cast in silicone, and the aptamer along with acrylamide and bis-acrylamide was seeded into the silicone mold. The DNA hydrogel was then fabricated using a simple UV curing protocol. The optimized DNA hydrogel was specific to calcium, used simple fabrication methods and had a fast, reversible signal response. Finally, in Aim 3, we developed the DNA hydrogel sensor into a wearable, integrated system with real-time fluorescence monitoring for testing in vivo. The microneedle array needed to be hydrated for the DNA aptamer to function, but polyacrylamide was too weak in its hydrated state to effectively pierce through skin epidermis. We demonstrated a method for strengthening our hydrogel system with polyethylene glycol diacrylate (PEGDA), while maintaining an optically translucent gel for detection purposes. We conducted piercing studies with a skin phantom on different microneedle array sizes and shapes, and determined that a 3x3 array of beveled microneedles required the least amount of force to pierce through a skin phantom. A custom complementary metal-oxide semiconductor (CMOS) system was developed to capture real-time fluorescence signals from the microneedle array, which correlated to calcium levels in vitro. This setup was then validated in a rat study. In this dissertation, we demonstrated methods for monitoring human biosignals using signal processing techniques, material innovations and integrated sensing platforms. While a work in progress, this dissertation is a step towards realizing the goal of decentralized, connected health for earlier detection and better management of disease.

No description available.

<p><strong>Background: </strong>Myocardial injury after noncardiac surgery (MINS) increases the risk of 30-day mortality. Intraoperative hemodynamic events (i.e., tachycardia, bradycardia, hypotension, and hypertension) may contribute to developing MINS.</p> <p><strong>Objectives: </strong>To determine if the addition of the duration spent within predefined intraoperative systolic blood pressure (BP; mmHg) (i.e.,160-199 and ≥200) and heart rate (HR; bpm) (i.e.,100-140 and >140) hemodynamic bands improved the prediction of Day 1 MINS (i.e., postoperative troponin T elevation ≥0.03 ng/ml within the first day after surgery) beyond preoperative risk model prediction.</p> <p><strong>Methods: </strong> Prospective observational data was used to developed a baseline risk model to predict Day 1 MINS. Preoperative HR, systolic BP, and hemoglobin as well as intraoperative duration spent within each predefined hemodynamic band were explored to identify optimal thresholds for the prediction of Day-1 MINS. Preoperative variables were added to the baseline risk model to create a preoperative model. Intraoperative variables were then added to the preoperative risk model to create the final model. Models were compared using discrimination (c-statistic) and net reclassification index (NRI).</p> <p><strong>Results: </strong>Adding preoperative hemoglobin ≤105 g/dL, systolic BP110 improved baseline model discrimination (0.783 to 0.792, p5min; HR >100 for >147min; systolic BP59min and systolic BP >160 for >42min further improved discrimination (0.8; p</p> <p><strong>Conclusion:</strong> Adding intraoperative hemodynamic durations significantly improved Day-1 MINS model discrimination and risk stratification compared to the baseline risk model.</p> / Master of Health Sciences (MSc)

Yes / Heart failure affects 26 million people globally, and the optimal management of medicines is crucial for patients, particularly when their care is transferred between hospital and the community. Optimising clinical outcomes requires well-calibrated cross-organisational processes with staff and patients responding and adapting to medicines changes. The aim of this study was to assess the feasibility of implementing a complex intervention (the Medicines at Transitions Intervention; MaTI) co-designed by patients and healthcare staff. The purpose of the intervention was to optimise medicines management across the gaps between secondary and primary care when hospitals handover care. The study objectives were to (1) assess feasibility through meeting specified progression criteria to proceed to the trial, (2) assess if the intervention was acceptable to staff and patients, and (3) determine whether amendment or refinement would be needed to enhance the MaTI. The feasibility of the MaTI was tested in three healthcare areas in the North of England between July and October 2017. Feasibility was measured and assessed through four agreed progression to trial criteria: (1) patient recruitment, (2) patient receipt of a medicines toolkit, (3) transfer of discharge information to community pharmacy, and (4) offer of a community pharmacy medicines review/discussion or medicines reconciliation. From the cardiology wards at each of the three NHS Acute Trusts (sites), 10 patients (aged ≥ 18 years) were recruited and introduced to the 'My Medicines Toolkit' (MMT). Patients were asked to identify their usual community pharmacy or nominate a pharmacy. Discharge information was transferred to the community pharmacy; pharmacists were asked to reconcile medicines and invited patients for a medicines use review (MUR) or discussion. At 1 month following discharge, all patients were sent three questionnaire sets: quality-of-life, healthcare utilisation, and a patient experience survey. In a purposive sample, 20 patients were invited to participate in a semi-structured interview about their experiences of the MaTI. Staff from hospital and primary care settings involved in patients' care were invited to participate in a semi-structured interview. Patient and staff interviews were analysed using Framework Analysis. Questionnaire completion rates were recorded and data were descriptively analysed. Thirty-one patients were recruited across three sites. Eighteen staff and 18 patients took part in interviews, and 19 patients returned questionnaire sets. All four progression to trial criteria were met. We identified barriers to patient engagement with the intervention in hospital, which were compounded by patients' focus on returning home. Some patients described not engaging in discussions with staff about medicines and lacking motivation to do so because they were preoccupied with returning home. Some patients were unable or unwilling to attend a community pharmacy in person for a medicines review. Roles and responsibilities for delivering the MaTI were different in the three sites, and staff reported variations in time spent on MaTI activities. Staff reported some work pressures and staff absences that limited the time they could spend talking to patients about their medicines. Clinical teams reported that recording a target dose for heart failure medicines in patient-held documentation was difficult as they did not always know the ideal or tolerable dose. The majority of patients reported receiving the patient-held documentation. More than two-thirds reported being offered a MUR by their community pharmacists. Delivery of the Medicines at Transitions Intervention (MaTI) was feasible at all three sites, and progression to trial criteria were met. Refinements were found to be necessary to overcome identified barriers and strengthen delivery of all steps of the intervention. Necessary changes to the MaTI were identified along with amendments to the implementation plan for the subsequent trial. Future implementation needs to take into account the complexity of medicines management and adaptation to local context. / This study is funded by the National Institute for Health Research (NIHR) (Programme Grants for Applied Research (Grant Reference Number RP-PG-0514-20009)). The study is also supported by the NIHR Yorkshire and Humber Patient Safety Translational Research Centre.

The most common cause of death is cardiovascular disease, with a prevalence of 3,500 per 100,000 people worldwide (Pirani and Khiavi 2017). Tissue ischemia due to cardiovascular diseases induces disorder such as myocardial infarction, pulmonary arterial hypertension, and atherosclerosis. In ischemic cardiomyopathy, heart failure is caused by the cardiac muscle getting damaged due to ischemia and losing its ability to pump blood properly. These ischemic conditions can affect cellular homeostasis and metabolism, which can result in cardiovascular dysfunction. Considering the effect of ischemic cardiomyopathy on the global population, it is vital to understand the impact of ischemia on the cardiac cells and how ischemic condition changes different cellular functions through epigenetic changes. Epigenetics has been associated with some cardiovascular disease risk factors, so reversing or modifying these changes through drug therapy could reverse or prevent the effects of CVD. A combination of genetics and environmental factors can regulate gene expression dynamically on a physiological level. Additionally, post-translational modifications (PTM) play an important role in cellular gene expression through epigenetic changes. Neonatal rat primary cardiomyocytes were used to understand the changes in acetylation during ischemic conditions compared to normoxic conditions. Mass spectrometry was performed on proteins isolated from these samples to analyze changes in acetylation due to ischemia. Analysis was performed to link genomic information with higher-order functional information for the identified proteins. These acetylated changes were found to be localized in different subcellular organelles and involved various molecular functions and biological processes. This study aims to identify global acetylation changes in cells exposed to ischemic conditions to identify therapeutic targets to prevent and treat ischemia-mediated heart disease.

Thesis (MScEng (Mechanical and Mechatronic Engineering))--University of Stellenbosch, 2009. / Elderly patients suffering from aortic valvular dysfunction are often denied aortic valve replacement due to the fact that they are classified as too old and fragile to handle the physical stress of open-heart surgery and cardio-pulmonary bypass. There exists a need for an alternative solution which places less physical stress on the body. The development of a percutaneous aortic heart valve (PAHV), which may be implanted through a minimally invasive procedure, will provide a solution to old and fragile patients who otherwise have a very limited life expectancy. The development of such a device entails a costly and time-consuming process which involves a number of phases, including a prototype development phase, an in-vitro testing phase, an animal trial phase and a human trial phase. This thesis focuses on the design and analysis of the stent component for a PAHV, suitable for implantation in sheep (animal trial phase). The process of developing a first prototype, involved an analysis of the stent design requirements. This analysis was followed by a concept generation phase as well as comprehensive finite element (FE) analyses of the most promising concepts. The objective of the FE analyses was to determine the effects of a variation in strut width on the performance characteristics of the concepts. Based on the results of the FE analyses, final geometries were selected for each of the two most promising concepts. Subsequent to the selection of the final geometries, a number of prototypes were manufactured. The prototypes were subjected to an electro-polishing process. An experimental analysis was also conducted on the prototypes to evaluate the accuracy of the (FE) simulations as well as the actual performance of the stent prototypes. The results of the FE analyses and experimental analyses indicated that strut width had a substantial influence on the parameters that were defined to characterise stent performance. The results of the analyses also highlighted the advantages and disadvantages of each concept and aided in identifying the concept that would be most suitable for the required application. Limitations of the study were identified and recommendations were made to assist the continued research and development of the device.