Submitted in fulfillment of the requirements for the Degree of Masters in Technology: Cardiology, Durban University of Technology, 2012. / Cardiomyopathies and their resultant heart failure (HF) remain a major cause of cardiovascular morbidity and mortality (Wood and Picard, 2004). Idiopathic dilated cardiomyopathy (IDCMO) is a primary myocardial disease of unknown cause, characterized by left ventricular (LV) or biventricular dilatation and impaired myocardial contractility. Dilated cardiomyopathy (DCMO), along with rheumatic heart disease and hypertension (HPT), is one of the leading causes of HF in Africa. In fact, in an epidemiology study of 884 patients in Soweto, IDCMO was the second major cause of HF. Thirty five percent of patients in the study, with HF, had IDCMO (Sliwa, Damasceno, Mayosi, 2005). Methodology: Patients referred to the cardiomyopathy (CMO) clinic at Chris Hani Baragwanath hospital, situated in the echocardiographic lab, were recruited, provided they satisfied the exclusion and inclusion criteria and were enrolled after obtaining voluntary informed consent. From May 2009 to September 2010, 70 patients with IDCMO were recruited for this trial. Patients with DCMO were identified by means of echocardiographic criteria which included a left ventricular ejection fraction (LVEF) of less than 45% and an end diastolic dimension (EDD) of greater than of 52 mm (2D in long parasternal axis). Results: In the present study the prevalence of left ventricular (LV) thrombus in patients with IDCMO was 18.6%. When using Univariate logistic regression, the only independent predictors of LV thrombus formation was LVEF and age. However, when multivariate logistic regression analysis was applied to the data, the only predictor with a significant association was age. The reason for this is not clear. It is postulated that perhaps younger patients have differences in the pathophysiology of their disease such as a greater smoldering inflammatory component which may therefore predispose them to thrombus formation. For example the presence of IL-6 may be important in the formation of LV clot in cases of LV dysfunction (Sosin, Bhatia, Davis, Lip, 2003). The association between LVEF and LV thrombus was borderline significant. Conclusion: The prevalence of LV thrombus formation in this cohort of patients with IDCMO was 18.6%. Echocardiographic parameters alone cannot predict which patients are more likely to develop thrombus formation. / National Research Foundation / M

Heart failure (HF) is a serious, life limiting chronic illness and is the most common cause of <30-day hospital readmission, which is costly both in its profound negative impact on patient mortality and quality of life, and in economics. Limited access to care in rural communities increases the prevalence of hospitalizations for heart disease in rural areas. The aims of this project using data mined from Arizona Health Sciences Center Clinical Research Data Warehouse, are to define clinical events (fever, pain, changes in respiratory status, change in level of consciousness, changes in output, bleeding, and suicide ideation) for patients with heart failure, and determine what assessment values are for chronically ill patients and compare to "normal" assessment values for non-chronically ill patients. A literature review was completed to determine how to define clinical events for chronically ill patients with HF, and how decision making is used at home to manage chronic illness. Assessment value data was mined from the clinical research data warehouse and compared to “normal” assessment values, with identification of associations between clinical events and action taken in the hospital. The project results support that there are differences in "normal" assessment values for fever, pain, and change in respiratory status between chronically ill patients with HF, and non-chronically ill patients; there was insufficient data to define bleeding, change in output, or suicide ideation. Impacts to care include earlier recognition of worsening HF symptoms that could result in an earlier call or visit to primary care provider forestalling the need for emergent care and hospital readmission. Application of the mined clinical may inform development of evidenced-based algorithm to guide decision-making at home, and it may also provide the foundation for the development of a tool for patient use to prevent <30-day hospital readmission.

Thesis (MPH) -- University of Limpopo, 2007. / Aim of the study: To determine knowledge of CPR and heart attack or cardiac arrest signs and symptoms among university students. Study Design: A questionnaire based descriptive, cross – sectional study. Setting: University of Limpopo – Turfloop Campus in Limpopo Province of South Africa. Subjects: A total sample of 400 students participated in the study. The sample was selected randomly using simple random sampling techniques. Outcome measures: The faculty, age, gender and level of study were determined as well as the knowledge each student has on signs and symptoms of impending heart attack and CPR. Results: Of the 400 students only 26% (n=104) knew the signs and symptoms of an impending heart attack as well as out of hospital management of heart attack by performing CPR. There were differences between and within faculties, age groups, gender and level of study. Based on the Bonferroni test the student from faculty of Sciences, Health and Agriculture are more likely (p-value 0017) to know when to perform CPR compared to students from other faculties. Level of study is not associated (p-value 0128) with how much the students know about the timing and indications of CPR. Overall female students performed worse with 79% (n=123) responding incorrectly to the questions compared to 69% (n=169) males. Conclusion: Based on the results of this study it safely can be concluded that the students’ knowledge of signs and symptoms of an impending heart attack and CPR procedure is poor. It is therefore important for the university as a center of teaching and learning to consider including as part of university curriculum, basic life support v and first aid courses which include CPR. The inclusion of basic life support and first aid in university curriculum will prepare students to be able to effectively manage out of hospital heart attack and reduce mortality resulting from the latter. The findings of this study might to a certain extent be reflecting what the public’s knowledge on the subject is, hence the need for the policy makers to take serious note of the findings when public health promotion programmes are developed.

Myocardial ischemia, infarction, heart failure and arrhythmias are the manifestations of coronary artery disease. Reduction of ischemic damage is a major concern of cardiovascular biology research. As per recent studies, the mitochondrial ATP-sensitive potassium channel (mitoKATP) opening is believed to play key role in the physiology of cardioprotection, protection against ischemia-reperfusion injury or apoptosis. However, the structural information of mitoKATP is not precisely known. Elucidating the structural integrity and functioning of the mitoKATP is therefore a major goal of cardiovascular biology research. The known structure and function of the cell ATP-sensitive potassium channel (cellKATP) is functional in interpreting the structural and functional properties of mitoKATP. The primary goal of my research was to characterize the activity of mitoKATP in the isolated mitochondria from the control mouse heart. The mitoKATP activity, if preliminarily characterized in the control strains through the light scattering technique, then the structure of the channel could possibly be established and analyzed by means of the transgenic model and with the help of immunological techniques such as western blotting and immunoflorescence. With this experimental model it was possible to demonstrate that the mitoKATP activity in control mouse heart mitochondria is activated by potassium channel openers (KCOs) such as diazoxide and cromakalim and activators of mitoKATP such as PMA (phorbol12 myristate-13-acetate), and inhibited by KATP inhibitors such as glibenc1amide and 5-hydroxydecanoate (5 HD). It was evident that the KATP activity in mouse heart mitochondria was comparable to that exhibited by the rat heart mitochondria. The various selective and non-selective activators and inhibitors of the channel elicited their activity at a similar concentration used for the rat heart mitochondria. The results were reproducible in five independent experiments for each combination, further reinforcing the significance of existing channel activity in the mouse heart mitochondria.

Indiana University-Purdue University Indianapolis (IUPUI) / Dishevelled-associated activator of morphogenesis 1 (Daam1), a member of the formin protein family, has been implicated in the non-canonical Wnt mediated Planar Cell Polarity (PCP) signaling pathway. Although the studies in Drosophila Daam1 and Xenopus Daam1 generated inconsistent conclusions regarding the function of Daam1, the biological function of mammalian Daam1 was not evaluated. In this study, we used a mouse promoter trap technology to create Daam1 deficient mice to analyze the role of Daam1 in embryonic development and organogenesis. Daam1 is highly expressed in the developing heart. The majority of Daam1 mutant mice died between embryonic day 14.5 and birth, exhibiting a variety of heart defects, which include ventricular noncompaction, ventricular septal defects, and double outlet right ventricle. About 10% mutant mice survive to adulthood, and these survivors do not show significantly compromised heart function based on echocardiographic analyses. However, all of these mutant survivors have ventricular noncompaction with a range of severities. A conditional rescue experiment using a cardiac specific Cre mouse line, Nkx2-5Cre, confirmed that the cardiac defects are the primary cause of death in Daam1 mutants. Both in vivo and ex vivo analyses revealed that Daam1 is essential for regulating non-sarcomeric filamentous actin assembly in cardiomyocytes, which likely contributes to cardiac morphogenesis and ventricular wall maturation. Biochemical studies further suggested that Daam1 is not a key signaling component in regulating the activation of small GTPases, such as RhoA, Rac1 and Cdc42. In conclusion, our studies demonstrated that Daam1 is essential for cardiac morphogenesis likely through its regulation of cytoskeletal architecture in the developing cardiomyocytes. / indefinitely

Indiana University-Purdue University Indianapolis (IUPUI) / Congenital heart defects occur in approximately one percent of births every year, which makes it the most frequently occurring congenital defect in patients. The aim of this project was to use two mutant neural crest (NC) mouse models to study the mechanisms underlying congenital heart failure in utero. The first mouse model was a Pax3 systemic knockout, which was lethal by mouse gestational day 14, and had appreciably reduced numbers of migratory NC cells. The second mouse model was a Wnt1Cre-mediated NC genetic cell ablation model, which was surprisingly viable and survived to birth, despite an apparent lack of migratory NC cells. The resultant data indicated that both mouse models had similar heart structural defects including persistent truncus arteriosus, which was due to fewer or no migratory cardiac NC cells. However, in utero heart function was appreciably perturbed in Pax3 mutants when compared to that of the ablated mutant model. The loss of embryonic cardiac function in Pax3 mutants was directly attributed to a substantial decrease in the activity of the beta-adrenergic pathway. This was due to a lack of proper specification of trunk NC cells, leading to diminished levels of circulating catecholamine levels in the embryo. To definitively confirm this conclusion, poor cardiac function was successfully restored by pharmacological stimulation of the beta-adrenergic pathway via administration of isoproterenol and forskolin to pregnant dams, which led to embryonic survival of Pax3 mutants to birth. By comparison of these two mutant mouse models, perturbation in the beta-adrenergic pathway was identified as the underlying mechanism responsible for in utero heart failure and lethality in Pax3 mutant embryos. The results of this study are expected to be significant in developing future therapeutic targets for congenital heart failure in prenatal and newborn patients.

Acute congestive heart failure is a leading cause of morbidity and mortality. Patients often undergo repeated hospitalizations with an annual cost in excess of $32B dollars. Early detection of impending acute congestion allows for pharmaceutical interdiction that prevents hospitalization, improves outcomes, and reduces healthcare spending. A subcutaneous implantable monitoring device that detects impending acute congestive heart failure by using heart sounds may provide a valuable tool that can be used to titrate heart failure medications to prevent acute heart failure requiring hospitalization. The device may be used to measure changes in the intervals between the R-wave and S1 and S2 heart sounds, and to detect evolving S3 and S4 heart sounds consistent with volume overload. The amplitudes of S1 and S3 heart sounds change as heart failure patients' symptoms worsen. Designing a non-invasive, external device, capable of recording heart sounds and EKGs in patients undergoing pharmaceutical regression of acute congestive heart failure in a hospital setting may give important insight into the nature of heart sound and EKG changes that occur in patients during progression of acute heart failure while they lead their day-to-day lives. This thesis details the design of a portable, non-invasive device, worn externally on the left-pectoral muscle, capable of continuously recording human EKG signals and heart sounds (through custom MEMS accelerometer technology) over a period of two days. Hardware testing for the scope of this thesis exclusively involved healthy volunteers.

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Nine male CHD patients volunteered for testing to determine variations in heart rate response (HR), walk-jog velocity (W) and compliance to the target heart rate zone under three monitoring conditions. Determination of variations in W, peripheral perceived exertion (RPE_L) chest perceived exertion (RPE_C) and post-exercise lactate accumulation (La) during exercise which was held constant between 60-80% maximum HR reserve were also made. Procedures consisted of three 20 min walk-jog exercise conditions. First, two baseline condition (BC) trials were performed on separate days with exercise intensity regulated through intermittent defibrillator-ECG HR checks and radial/carotid artery palpation. Next, continuous telemetry monitoring of HR by staff was added during a single exercise trial (TC). Finally, two Exersentry_Rcondition (EC) trials were performed on separate days with continuous feedback concerning HR response provided to the patient via Exersentry_R devices. Evaluation of HR and W revealed no significant variation between conditions. However, % target HR reserve attained was significantly (p>0.05) lower during early and late BC, as compared to TC. Furthermore, "frequency in" vs "frequency out" of target HR zone was significantly (p>0.05) greater during EC, as compared to TC. During EC, no significant variations in HR, W, La, RPE_L and RPE_C were noted. Correlation coefficient values between 0.76-0.95 and 0.58-0.80 were reported for RPE_L and RPE_C, respectively. This data suggested that continuous feedback concerning HR response resulted in the greatest compliance to the target HR zone. With the exception of the first five min of EC, only RPE_L reliably mirrored HR and W. Index terms: Intermittent heart rate monitoring, continuous heart rate monitoring, heart rate response, walk-jog velocity, target heart rate compliance, peripheral perceived exertion, chest perceived exertion, post-exercise lactate accumulation. / M.S.