Dynamic contrast enhanced (DCE) cardiac magnetic resonance imaging (MRI) is well-established as a non-invasive method for qualitatively detecting obstructive coronary artery disease (CAD) which can impair myocardial blood flow and may result in myocardial infarction. Mathematical modelling of cardiac DCE-MRI data can provide quantitative assessment of myocardial blood flow. Quantitative assessment of myocardial blood flow may have merit in further stratification of patients with obstructive CAD and to improve the diagnosis and prognostication of the disease in the clinical setting. This thesis investigates the development of a quantitative analysis protocol for cardiac DCE-MRI data. In the first study presented in this thesis, Fermi and distributed parameter (DP) modelling are compared in single bolus versus dual bolus analysis. For model-based myocardial blood flow quantification, the convolution of a model with the arterial input function (i.e. contrast agent concentration-time curve extracted from the left ventricular cavity) is fitted to the tissue contrast agent concentration-time curve. In contrast to dual bolus DCE-MRI protocols, single bolus protocols reduce patient discomfort and acquisition protocol duration/complexity but, are prone to arterial input function saturation caused in the left ventricular cavity by the high concentration of contrast agent during bolus passage. Saturation effects can degrade the accuracy of quantification using Fermi modelling. The analysis presented in this study showed that DP modelling is less dependent on arterial input function saturation than Fermi modelling in eight healthy volunteers. In a pilot cohort of five patients, DP modelling detected for the first time reduced myocardial blood flow in all stenotic vessels versus standard clinical assessments. In the second study, it was investigated whether first-pass DP modelling can give accurate myocardial blood flow, against ideal values generated by numerical simulations. Unlike Fermi modelling which is convolved with only the first-pass range of the arterial input function, DP modelling is convolved with the entire contrast agent concentration-time course. In noisy and/or dual bolus data, it can be particularly challenging to identify the end point of the first-pass in the arterial input function. This study demonstrated that contrary to Fermi modelling, myocardial blood flow analysis using DP modelling does not depend on the number of time points used for fitting. Furthermore, this data suggests that DP modelling can reduce the quantitative variability caused by subjectivity in selection of the first-pass range in cardiac MR data. This in turn may help to facilitate the development of more automated software algorithms for myocardial blood flow quantification. In the third study, Fermi and DP modelling were compared against invasive clinical assessments and visual MR estimates, to assess their diagnostic ability in detecting obstructive CAD. A single bolus DCE-MRI protocol was implemented in twentyfour patients. In per vessel analysis, DP modelling reached superior sensitivity and negative predictive value in detecting obstructive CAD compared to Fermi modelling and visual estimates. In per patient analysis, DP modelling reached the highest sensitivity and negative predictive value in detecting obstructive CAD. These studies show that DP modelling analysis of cardiac single bolus DCE-MRI data can provide important functional information and can establish haemodynamic biomarkers to non-invasively improve the diagnosis and prognostication of obstructive CAD.

Knowledge about cardiac and inflammatory biomarkers in patients with stable coronary artery disease (CAD) is limited. To address this, we analyzed 3072 patients (36% female) with a median follow-up of 10 years in the Leipzig LIFE Heart Study with suspected CAD with coronary angiography. Selected biomarkers included troponin T (hsTNT), N-terminal pro B-type natriuretic peptide (NT-proBNP), copeptin, C-reactive protein (hsCRP), and interleukin-6 (IL-6). Patients were stratified by CAD severity: CAD0 (no sclerosis), CAD1 (non-obstructive, i.e., stenosis < 50%), and CAD2 (one stenosis 50%). Group comparison (GC) included GC1: CAD0 + 1 vs. CAD2; GC2: CAD0 vs. CAD1 + 2. CAD0, CAD1, and CAD2 were apparent in 1271, 631, and 1170 patients, respectively. Adjusted for classical risk factors, hs-cTnT, NT-proBNP, and IL-6 differed significantly in both GC and hsCRP only in GC2. After multivariate analysis, hs-cTnT, NT-proBNP, and IL-6 remained significant in GC1. In GC2, hs-cTnT (p < 0.001) and copeptin (p = 0.014) reached significance. Ten-year survival in groups CAD0, CAD1, and CAD2 was 88.3%, 77.3%, and 72.4%. Incorporation of hs-cTnT, NT-proBNP, copeptin, and IL-6 improved risk prediction (p < 0.001). The studied cardiac and inflammatory biomarkers enable fast and precise non-invasive identification of mortality risk in CAD patients, allowing the tailoring of primary and secondary CAD prevention.

Background: Despite the fact that peripheral arterial disease (PAD) significantly increases the risk of cardiovascular mortality, it is significantly underdiagnosed and underrated. The purpose of this study was to evaluate the practice at a northeast Tennessee university primary care clinic regarding the diagnosis and treatment of PAD. Methods: A retrospective medical record survey was conducted to evaluate practice patterns in diagnosing and treating PAD in a university primary care clinic. A clinic population of 711 patients was selected using International Classification of Diseases-9 codes for coronary artery disease (CAD), cerebovascular disease (CVD), and/ or PAD. A sample of 180 patients (25.3%) was randomly selected using a systematic statistical method. Of these, 125 patients met the diagnostic criteria for CAD, CVD, and/or PAD. The study covered a 3-year period, from July 2001 until June 2004. Demographic and other data, including the use of antiplatelet therapy, were collected. Results: One hundred ten patients met all of the inclusion and exclusion criteria. Thirty-nine percent were males, and 61% were females. Overall, 79% had CAD, 53% had CVD, and 25% had PAD. Almost half of the patients had some combination of these. Only about 2% had PAD only compared with 36% with CAD only and 17% with CVD only. Although the prevalence of CAD and CVD (among other atherosclerotic vascular diseases) in our clinic was comparable to national figures, the prevalence of PAD was significantly lower (p = .004). The overall use of any antiplatelet agent was 84.2% for patients with only CAD and 80% for only CVD. There was not an adequate number of patients with only PAD to evaluate the use of antiplatelet therapy in this group. Conclusion: The low prevalence of PAD only (most PAD patients had coexisting CAD and CVD) indicates that PAD is underdiagnosed at our clinic. There was suboptimal use of aspirin and other antiplatelet drugs among patients with atherosclerotic vascular disease.

Ziel: Die Ergebnisse nach aortokoronarer Bypassoperation (CABG) unterscheiden sich bei Patienten mit schlechter linksventrikulärer Pumpfunktion deutlich von denen bei Patienten ohne Einschränkungen derselben. Das Ziel dieser Studie war die Untersuchung des Einflusses einer reduzierten linksventrikulären Ejektionsfraktion (LVEF), eines vergrößerten linksventrikulären enddiastolischen Volumenindexes (LVEDVI) und eines erhöhten linksventrikulären enddiastolischen Druckes (LVEDP) auf das postoperative "outcome". Material und Methodik: Im Rahmen dieser retrospektiven Studie wurden 148 Patienten mit einer koronaren Herzkrankheit (KHK) und eingeschränkter Ejektionsfraktion (EF / Aim: Results of coronary artery bypass grafting (CABG) in patients with poor left ventricular ejection fraction (LVEF) differ from those in patients with normal LVEF. The aim of the study was a investigation into the influence of reduced LVEF, augmented left ventricular enddiastolic volume index (LVEDVI) and elevated left ventricular enddiastolic pressure (LVEDP) on the outcome of CABG. Methods: 148 Patients with LVEF < 50% underwent CABG. Exercise tolerance and LVEF were determined pre- and postoperatively. Three subgroups were built to distinguish the influence of reduced LVEF on postoperative outcome. Group I: LVEF < 30%, group II: 30% < LVEF < 40%, group III: 40% < LVEF < 50%. Results: Exercise tolerance rised from a preoperatively mean of 70 Watt to 97 Watt postoperatively. Mean NYHA class was 2,7 pre- and 1,7 postoperatively. There were no significant differences in the results of the three subgroups. Perioperative mortality in group I was 6,3%. Actuarial 1 and 2 years survival in this group is at 81 and 70% respectively. These results differ clearly from those of group II and III. Perioperativ mortality was 2,2% in group II and 1,4% in group III. Actuarial 1 and 2 years survival is at 93 and 84% in group II and at 95 and 83% in group III. There was no difference in postoperative outcome of patients with LVEDP > 12mmHg in comparison to patients with LVEDP < 12mmHg. Patients with LVEDVI > 100 ml/m2 had a sifnificant higher peri- and postoperative mortality than patients with LVEDVI < 100 ml/m2. Mean LVEDVI of those patients, whose LVEF increased postoperatively, was 84 ml/m2. Patients with no change in LVEF had a mean LVEDVI of 122 ml/m2. Conclusion: CABG in patients with reduced LVEF improves exercise tolerance and quality of life. Poor LVEF (< 30%) and augmented LVEDVI are predicting higher peri- and postopertive mortality. Postoperative increase of LVEF is unlikely in patients with enlarged left ventricels.

Text in Afrikaans / Coronary artery disease (CAD) is a life-threatening disease. When heart patients in the treatment of their disease, due to certain subjugating discourses practised by the biomedical model or biomedicine, are treated in a way that contributes to their anxiety and they feel themselves marginalised by society, then CAD becomes even more threatening. The narrative-pastoral approach of this study aims to treat heart patients in a way that has a calming effect on them that could assist them to deal with their heart disease more efficiently. This study shows how a heart patient's illness stories can be centralised by means of narrative therapy and how a pastoral and ethical attitude of love and respect can produce a climate that's conducive to better health and well-being. I indicate how my methodology of participatory action research succeeds in making the heart patients active participants to the research project. Their active participation indicates that meaning is not created on their behalf in therapy; rather, they are responsible for the process of richer construction of meaning. I describe how the participants socially co-constructed alternative and richer descriptions of their illness. Futhermore, I point out how their richer descriptions of illness contribute to perceptible and measurable results that are of value to the heart patients. / Koronere hartvatsiekte (KHS) is 'n lewensbedreigende siekte. Wanneer hartpasiente in die behandeling van hul siekte vanwee sekere onderdrukkende diskoerse van siekte vanuit die biomediese model of biomedisyne s6 hanteer word dat dit spanning op hul plaas en deur die samelewing gemarginaliseer word, word KHS des te meer gevaarlik. In hierdie studie gaan dit oor 'n narratief-pastorale benadering wat hartpasiente op 'n kalmerende manier hanteer sodat hulle kan kom tot 'n meer doeltreffende hantering van hul hartsiekte. Hierdie studie toon aan hoe hartpasiente se siekteverhale deur middel van narratiewe terapie gesentreer word en hoe 'n etiese en pastorale gesindheid van liefde en respek 'n klimaat skep wat bevorderlik is vir beter gesondheid en welwese. Ek dui aan hoe my metodologie van deelnemende aksienavorsing daarin geslaag het om die hartpasiente aktiewe deelnemers te maak aan die navorsingsprojek. Hul aktiewe deelname impliseer dat betekenis nie in terapie vir hulle geskep word nie, maar dat hulle self skeppend betrokke is in die proses van ryker betekeniskonstruering. Ek beskryf hoe die deelnemers altematiewe en ryker beskrywings van hul siekte sosiaal ko-konstrueer. Ek dui verder aan hoe hul ryker beskrywings van siekte bydra tot sigbare en meetbare resultate wat vir hartpasiente van waarde is. / Practical Theology / D. Th. (Praktiese Teologie)

Text in Afrikaans / Coronary artery disease (CAD) is a life-threatening disease. When heart patients in the treatment of their disease, due to certain subjugating discourses practised by the biomedical model or biomedicine, are treated in a way that contributes to their anxiety and they feel themselves marginalised by society, then CAD becomes even more threatening. The narrative-pastoral approach of this study aims to treat heart patients in a way that has a calming effect on them that could assist them to deal with their heart disease more efficiently. This study shows how a heart patient's illness stories can be centralised by means of narrative therapy and how a pastoral and ethical attitude of love and respect can produce a climate that's conducive to better health and well-being. I indicate how my methodology of participatory action research succeeds in making the heart patients active participants to the research project. Their active participation indicates that meaning is not created on their behalf in therapy; rather, they are responsible for the process of richer construction of meaning. I describe how the participants socially co-constructed alternative and richer descriptions of their illness. Futhermore, I point out how their richer descriptions of illness contribute to perceptible and measurable results that are of value to the heart patients. / Koronere hartvatsiekte (KHS) is 'n lewensbedreigende siekte. Wanneer hartpasiente in die behandeling van hul siekte vanwee sekere onderdrukkende diskoerse van siekte vanuit die biomediese model of biomedisyne s6 hanteer word dat dit spanning op hul plaas en deur die samelewing gemarginaliseer word, word KHS des te meer gevaarlik. In hierdie studie gaan dit oor 'n narratief-pastorale benadering wat hartpasiente op 'n kalmerende manier hanteer sodat hulle kan kom tot 'n meer doeltreffende hantering van hul hartsiekte. Hierdie studie toon aan hoe hartpasiente se siekteverhale deur middel van narratiewe terapie gesentreer word en hoe 'n etiese en pastorale gesindheid van liefde en respek 'n klimaat skep wat bevorderlik is vir beter gesondheid en welwese. Ek dui aan hoe my metodologie van deelnemende aksienavorsing daarin geslaag het om die hartpasiente aktiewe deelnemers te maak aan die navorsingsprojek. Hul aktiewe deelname impliseer dat betekenis nie in terapie vir hulle geskep word nie, maar dat hulle self skeppend betrokke is in die proses van ryker betekeniskonstruering. Ek beskryf hoe die deelnemers altematiewe en ryker beskrywings van hul siekte sosiaal ko-konstrueer. Ek dui verder aan hoe hul ryker beskrywings van siekte bydra tot sigbare en meetbare resultate wat vir hartpasiente van waarde is. / Philosophy, Practical and Systematic Theology / D. Th. (Praktiese Teologie)