Thèses sur le sujet « Cardiolgoy »

The first topic addressed in this thesis was the characterization of a new hybrid PET/CT scanner (Discovery-690); that was later used for all of the studies (experimental and clinical)performed in this work. Subsequently an antropomorphic static cardiac phantom is described. This was used to analyze the performances of different reconstruction algorithms, encompassing di fferent levels of information such as: i) the Time Of Flight (TOF) of the photons and ii) the Point-Spread-Function (PSF) of the PET tomograph. A problem, own of cardiac studies in PET, is the motion blur due to the cardiac beat and to the breath of the patient. To study the e ffects of this combined motion, both quantitatively and qualitatively, a moving mechanical phantom was built, that executed both movements in a separate and controlled way. After this investigation this phantom was exploited to evaluate the e cacy of gating techniques (cardiac and respiratory), by using single and double gating. These techniques were also applied to patient data. Double gating revealed to be able to provide better spatial resolution but with noise levels too high for diagnostic purposes. To overcome this problem while maintaining the full spatial resolution two registration techniques were proposed. The fi rst one consists in an affi ne registration that can be applied to correct only for respiratory motion. The second technique aims at registering all of the gates using an elastic morphing technique. This is achieved by using a map of the myocardial surface to build a Thin-Plate-Spline deformation field, using a segmentation algorithm. Both techniques allowed the reduction of the noise. In both phantom and patient studies promising quality improvements were obtained. The last chapter of the thesis involved the quanti cation of absolute cardiac perfusion analyzing 13NH3 PET studies with kinetic models. Initially the mathematical proprieties of the models proposed to analyze this tracer were assessed. Following the e ect of the image reconstruction algorithms on the parameters quanti ed with a speci c model were assessed. Two di erent software programs that allow perfusion quanti cation were also compared. The results of the studies described allowed the de nition of a clinical 13NH3 PET protocol, currently in use.

La presencia de enfermedad cardiaca puede tener repercusiones serias sobre la salud y el bienestar de los equinos pero el riesgo a las personas, asociado con el desarrollo de colapso cardiovascular o de muerte súbita cardiaca hacen de la cardiología equina una disciplina con implicaciones que van más allá de la salud animal. La tesis aquí presentada trata de aportar conocimientos sobre problemas cardiacos equinos. En el primer estudio de esta tesis se estudió los efectos de la hemorragia aguda en la concentración plasmática de un marcador específico de daño miocárdico, como es la troponina cardiaca I, y en el desarrollo de arritmias cardiacas. Para realizar este estudio diseñamos un estudio prospectivo en el que un grupo de caballos con hemorragia aguda se comparó a un grupo control. El estudio determinó que la hemorragia aguda causa daño miocárdico que puede ser detectado midiendo la concentración plasmática de troponina cardiaca I y que la presencia de arritmias es frecuente en caballos hospitalizados debido a la presencia de hemorragia aguda. EL segundo estudio de esta tesis se diseñó para estudiar la apariencia clínica, ecocardiográfica y anatomopatológica de la cardiomiopatía hipertensiva en caballos. Diseñamos un estudio retrospectivo en el cual se revisaron los archivos de la Universidad de Pensilvania desde 1995 a 2011 para encontrar casos con hipertrofia del miocardio del ventrículo izquierdo e hipertensión. A partir de esta información se describió la presencia de cardiomiopatía hipertensiva como una comorbilidad en caballos con laminitis y fallo renal crónico. Este problema clínico no había sido descrito previamente en equinos. La cardiomiopatía hipertensiva debería de considerarse en caballos con hipertensión y se debe añadir a la lista de diagnósticos diferenciales en los caballos que presentan hipertrofia del ventrículo izquierdo. El tercer estudio de esta tesis investigó la presencia de un estado de hipercoagulación en caballos con fibrilación atrial. La fibrilación atrial es la arritmia clínicamente mas relevante en caballos y humanos y en humanos causa un estado de hipercoagulación que provoca que las complicaciones tromboembólicas sean la mayor causa de morbilidad y mortalidad en estos pacientes. Diseñamos un estudio prospectivo control en el cual los tests de coagulación más utilizados en medicina equina se realizaron en muestras de sangre obtenidas de caballos con fibrilación atrial y de un grupo control. La proporción de caballos con D-dímeros, paneles de coagulación y resultados anormales fue mayor en el grupo de caballos con fibrilación atrial. La antitrombina fue significativamente mas baja en el grupo de caballos con fibrilación atrial. Ninguno de los caballos mostró signos clínicos de hipercoagulación o tromboembolismo. Este estudio demostró que los caballos en fibrilación atrial presentan un estado subclínico de hipercoagulacion sin sintomatología clínica de tromboembolismo. Como conclusión, los tres estudios que forman parte de esta tesis doctoral han contestado cuestiones relevantes que no habían sido investigadas previamente. La hemorragia aguda causa daño miocárdico y arritmias en caballos. Caballos con laminitis y enfermedad renal crónica pueden desarrollar cardiomiopatía hipertensiva y los caballos con fibrilación atrial permanecen en un estado de hipercoagulabilidad sin consecuencias tromboembólicas.
The presence of cardiac disease can have serious repercussions to horses’ health and wellbeing but the risks for humans associated with equine cardiovascular collapse or sudden cardiac death make equine cardiology a discipline that has implications that go beyond animal health. The thesis presented here was designed to gain further knowledge in equine cardiac problems The first study of this thesis studied the effects of acute hemorrhage on the plasma concentration of a marker of myocardial injury (cTnI) and in the development of cardiac arrhythmias. We designed a prospective controlled study in which a group of horses presented with acute hemorrhage were compared to a control group. We concluded that acute hemorrhage results in myocardial injury that can be detected by measuring cTnI and that arrhythmias are frequent in hospitalized horses with acute hemorrhage. The goal of the second study of this thesis was to study the clinical, echocardiographic and pathological appearance of hypertensive cardiomyopathy (HC) in horses. To achieve this goal we designed a retrospective study in which the medical records of the University of Pennsylvania’s New Bolton Center (between 1995 and 2011) were searched for the presence of horses with myocardial hypertrophy and hypertension. We described the presence of HC as a comorbid diagnosis in horses with laminitis or chronic renal failure. This clinical entity had not been previously diagnosed in horses. Hypertensive cardiomyopathy should be borne in mind when evaluating horses with hypertension and added to the list of differentials diagnoses for horses that present left ventricular hypertrophy. The third part of this thesis had the motivation of investigating the presence of a hypercoagulable state in horses with atrial fibrillation. Atrial fibrillation is the most common and clinically relevant arrhythmia in horses and in humans. Humans in atrial fibrillation are in a hypercoagulable state that makes stroke and thromboembolism the major cause of morbidity and mortality in patients with this rhythm disturbance. We designed a prospective controlled study in which common tests to evaluate coagulation and fibrinolysis in horses were performed on blood samples obtained from equine patients with atrial fibrillation and in a control group. The proportion of horses with abnormal D-dimer concentrations, abnormal coagulation profiles and the proportion of abnormal coagulation tests was larger in the atrial fibrillation group than in the control group. Antithrombin activity was lower in the atrial fibrillation group. No clinical signs of hypercoagulability or thrombogenesis were detected in any of the horses. This study demonstrated that atrial fibrillation causes a state of hypercoagulability in horses without thromboembolic consequences. In conclusion, the three studies have contributed to the body of knowledge in equine cardiology and have answered relevant questions that had not been previously investigated. Acute hemorrhage causes myocardial injury and arrhythmias during acute hemorrhage in horses. Horses with laminitis or chronic renal failure can develop HC and horses in atrial fibrillation present subclinical hypercoagulation without thromboembolic consequences.

Le travail présenté dans ce document utilise les méthodes de recherche qualitative pour étudier (1) la fin-de-vie et (2) le consentement dans le domaine de la cardiologie. Dans une première étude, nous avons cherché à décrire et comprendre le vécu des médecins, des infirmières et des aides-soignants dans le Service de Cardiologie vis-à-vis des situations de fin-de-vie, en particulier chez les patients souffrant d’insuffisance cardiaque. Nos résultats montrent que globalement, la cardiologie est considérée comme une discipline active et à visée curative ; cette attitude est particulièrement prononcée chez les médecins, qui ont peu l’habitude d’affronter des situations de fin-de-vie et qui sont parfois réticents à l’idée d’initier des discussions sur ce sujet avec les patients. Les infirmières et les aides-soignants ont un rôle plus axé sur le soin et le confort, et sont donc plus ouverts à la possibilité de discuter de la fin-de-vie avec les malades. Cependant, l’intervention des infirmières et des aides-soignants ne peut se concevoir que dans les limites qui sont posées par les médecins : les infirmières ne prendraient jamais l’initiative d’aborder le sujet de la fin-de-vie avec un malade si le médecin ne l’a pas déjà fait. Les perspectives possibles pour harmoniser les approches vis-à-vis des situations de fin-de-vie incluent l’éducation des futurs médecins, des interventions pour améliorer les connaissances des soignants et augmenter leur confiance, ainsi que des projets de recherche pour identifier le moment opportun pour initier des discussions sur la fin-de-vie chez les patients avec insuffisance cardiaque, et les facteurs qui doivent inciter le cardiologue à demander une consultation spécialisée en soins palliatifs pour le malade. Enfin, une formation en communication serait de nature à améliorer les compétences des soignants en termes de communication sur la fin-de-vie en cardiologie.La deuxième partie de ce travail utilise la méthodologie de la théorie ancrée pour étudier les facteurs qui déterminent la décision d’un patient âgé d’accepter ou de refuser de participer à la recherche clinique. Nos résultats indiquent que les caractéristiques spécifiques de l’étude ne sont pas déterminantes dans la décision de participer ou non. Les patients qui ont d’autres préoccupations majeures (e.g. un deuil récent, ou un proche à soigner) n’ont pas les ressources mentales et/ou physiques nécessaires pour permettre la participation. Parmi les patients qui disposent des ressources mentales et/ou physiques nécessaires, il y a certains patients qui font preuve de beaucoup de confiance envers les professionnels de la santé. Ces patients s’engagent peu dans les décisions les concernant et suivent facilement les recommandations de ceux en qui ils ont confiance ; ils ont plutôt tendance à accepter. A l’inverse, certains patients s’engagement très activement dans leur propre santé et s’informent abusivement, sans prendre en considération la qualité scientifique des informations. Ils ne font pas confiance aux professionnels de la santé et ont plutôt tendance à refuser de participer à la recherche clinique. Enfin, dans une autre publication, nous discutons des dilemmes éthiques posés par la recherche de consentement pour la recherche clinique chez les patients gravement malades
The work presented in this thesis uses qualitative research methods in the field of cardiology to investigate (1) end of life issues and (2) consent issues. In a first study, we investigated the experiences and perceptions of physicians, nurses and nurses’ aides vis-à-vis end-of-life situations in the Cardiology department, with particular focus on heart failure patients. We found that overall, there is a predominantly active and curative attitude in cardiology, particularly among physicians, who are not accustomed to dealing with end-of-life situations and often reluctant to initiate these discussions with patients. Nurses and nurses’ aides have a more comfort-giving role, and as such, are more open to holding end-of-life conversations with patients and families. However, their actions are limited by what the physicians have previously discussed with the patient. Nurses do not address end-of-life questions with the patient if the physician has not already done so. Perspectives to harmonize the approach to end-of-life care in our Department include education of future healthcare providers, interventions to increase knowledge and boost confidence among healthcare providers, and research into the optimal time to initiate palliative care in heart failure patients, and consensual triggers that should prompt referral to specialist palliative care. Finally, training in communication would help to enhance healthcare providers’ skills in dealing with end-of-life issues in cardiology.In the second part of this work, using grounded theory methodology, we sought to investigate the factors that influenced the decision to accept or decline to participate in clinical research in elderly patients. Our results indicate that the individual characteristics of the trial are not the main determinants in the decision. Patients who have other major occupations in their life (e.g. recent bereavement, or a caregiving role for a spouse or relative) do not have sufficient mental and/or physical resources to be able to accept research participation. Among those who have the sufficient mental and/or physical resources, there are patients with high trust in the medical profession, who engage little in their own health and trust the healthcare provider to guide their decision; these patients tend to accept. Conversely, at the other end of the spectrum are patients who engage actively in their own health, read a lot, and ask many questions, and have low trust in the medical profession. These patients tend to refuse to participate in research. Finally, in a separate publication, we also discuss the ethical considerations related to obtaining consent in seriously ill patients

Background: Despite the favourable effects of new therapeutic approaches during the acute phase of cardiac diseases and consequent favourable short-term outcomes, post-acute management and long term prognosis still remain unsatisfactory. Cardiac rehabilitation (CR) is a multidisciplinary treatment with established beneficial effects for the vast majority of cardiac patients and universally considered an important aspect of secondary prevention. Although it has been shown to reduce both morbidity and mortality and it is a class I recommendation in the guidelines, its use remains still rather limited in Europe and in the rest of the world. Aim: The aim of this PhD research was to examine some aspects still little known, or unknown at all, in this field. In particular, the research aimed to evaluate safety and efficacy of a structured, exercise-based, CR in specific cohorts of patients: after transcatheter aortic valve implantation (TAVI), after left ventricular assist device (LVAD) implantation, and early after an acute myocardial infarction (AMI) in high risk subjects. Methods: All patients (78 TAVI, mean age 82.1±3.6 years, 42 LVAD, 63.4 ± 7.4 years, and 376 AMI, 64.4±12.3 years) were referred to the Institute Codivilla-Putti (in Cortina d’Ampezzo, BL, Italy) for a two week, in-hospital, CR training and comprehensive risk factors interventions early after the acute event (within two weeks TAVI and AMI, within two months after LVAD implantation). TAVI patients were compared with 80 consecutive peer patients who were admitted for CR in the same period after surgical aortic valve replacement (sAVR) and LVAD patients compared with 47 coeval chronic heart failure (CHF) patients who were admitted for CR in the same period after an acute heart failure event. In LVAD cohort, cardiac autonomic function was evaluated by means of heart rate variability. AMI patients were divided into 2 groups according to a 40% left ventricular ejection fraction (LVEF) cut-off at enrolment, in order to evaluate the influence of a reduced LVEF on the rehabilitative process; furthermore, in 326 patients a glucometabolic characterization was obtained by means of a standard oral glucose tolerance test (OGTT) in patients without known diabetes. In all patients the training protocol consisted of a low-medium intensity exercise protocol developed in three sets of exercises, 6 days per week: 30 min of respiratory workout, followed by an aerobic session on a cyclette (or on an arm ergometer in those patients who were not able to cycle) in the morning and, in the afternoon, 30 min of callisthenic exercises. Each session was supervised by a physician and a physiotherapist and all patients were ECG monitored by a telemetry system. Functional capacity was assessed by a six min walking test (6MWT) on admission, and a second test at discharge; when possible, a cardiopulmonary exercise test (CPET) was also performed. The Barthel Index (BI) was used as an autonomy index in TAVI and LVAD cohorts. In AMI patients rate of death, hospitalizations, smoke cessation, physical activity and adherence to pharmacological treatment were recorded at follow up (up to 5 years, median 2 years). Results: Despite the high risk profile of the population, the drop out rate was quite low (1.3% of TAVI, 1.1% of AMI and 11.9% of LVAD patients had to be transferred due to non fatal complications). All the subjects who completed the program had enhanced independence, mobility and functional capacity (mean BI increment was 9.9±12.6, p<0.01 and 11.9±10.5, p<0.01, in TAVI and LVAD patients respectively; mean 6MWT gain was 60.4±46.4 mt, p<0.01, 83.2±36.0 mt, p<0.05, 70.7±55.7 mt, p<0.01, in TAVI, LVAD and AMI patients, respectively). Analysing the specific cohorts, a smaller proportion of TAVI patients, compared with sAVR, was able to complete at least a 6MWT (82% vs 92%) or a CPET (61% vs 95%) but, in those who did, the distance walked at 6MWT at discharge did not significantly differ between the groups (272.7±108 vs. 294.2±101 mt, p=0.42), neither did the exercise capacity assessed by CPET (peak-VO2 12.5±3.6 vs. 13.9±2.7 ml/kg/min, p=0.16). At the end of the program, physical performance in LVAD patients was still generally poor, but not dissimilar from that found in CHF patients (peak-VO2 reached at CPET was 12.5±3.0 vs. 13.6±2.9 ml/kg/min, p=0.20). Evaluating AMI patients, subjects with LVEF<40% achieved significantly lower peak-VO2 at CPET than the controls (15.2±3.9 vs. 18.2±5.2 ml/kg/min, p<0.01). After OGTT administration, a high prevalence of abnormal glucose metabolism was found (54%). As expected, exercise capacity was poorer in diabetic and pre-diabetic patients when compared with normoglicemic (peak-VO2 at CPET 15.3±4.1 vs 17.9±4.8 vs 19.4±5.5 ml/kg/min, p<0.01). At follow up 73% of the subjects reported to exercise regularly, 77% of the smokers definitively quitted and a high adherence to the therapy was registered. Cardiac and all cause mortality resulted 5.0% and 8.0 % at 1 year and 8.0 % and 13.0 % at 5 years, respectively and resulted higher in older people and in those with lower LVEF. Conclusions: Patients who underwent TAVI and LVAD implantation are characterized by a long-term deconditioning status. In this perspective, benefit is not automatically achieved through high-technology interventions and pharmacological management alone. This study have shown that a short-term, supervised, exercise-based CR is feasible, safe and effective in elderly patients after TAVI, as well as after traditional surgery, and after LVAD implantation. An early CR programme enhances independence, mobility and functional capacity and should be encouraged in these subjects. An early and intensive CR, based on physical activity and counselling, resulted to be safe and effective also in high risk patients after AMI, both in the short and in the long period. Indeed, a significant improvement in functional capacity in the short term - independent from the basal ventricular function or glucometabolic status - and a high adherence to therapy and to lifestyle modifications in the long term were achieved. Despite the high risk profile of these patients, this produced a favourable effect on cardiac and total mortality.
Introduzione: Nonostante gli effetti favorevoli di nuovi approcci terapeutici durante la fase acuta delle malattie cardiache e conseguente prognosi più favorevole nel breve termine, la gestione della fase post-acuta di tali patologie e la prognosi a lungo termine rimane ancora insoddisfacente. La Riabilitazione Cardiologica (RC) è un trattamento multidisciplinare con chiari effetti benefici nella stragrande maggioranza dei pazienti cardiologici ed universalmente considerata un aspetto importante della prevenzione secondaria. Sebbene si sia dimostrata in grado di ridurre morbidità e mortalità e sia ormai un trattamento raccomandato in I classe nelle linee guida, il suo uso rimane ancora piuttosto limitato in Europa e nel resto del mondo. Scopo: Lo scopo del presente programma di ricerca è stato esaminare alcuni aspetti ancora pochi noti, se non del tutto sconosciuti, in questo campo. In particolare, la presente ricerca ha avuto lo scopo di valutare sicurezza ed efficacia di una RC strutturata, basata sull’esercizio fisico, in specifiche coorti di pazienti: dopo impianto di valvola aortica transcatetere (TAVI), dopo impianto di assistenza ventricolare sinistra (LVAD), e subito dopo infarto miocardico acuto (AMI) in soggetti ad alto rischio. Metodi: Tutti i pazienti (78 TAVI, età media 82.1±3.6 anni, 42 LVAD, 63.4 ± 7.4 anni, e 376 AMI, 64.4±12.3 anni) sono stati inviati presso l’Istituto Codivilla-Putti (Cortina d’Ampezzo, BL, Italia) per un periodo di riabilitazione cardiologica degenziale di due settimane, basato sull’allenamento fisico ed interventi sui fattori di rischio cardiovascolare, subito dopo l’evento acuto (entro due settimane dopo TAVI ed AMI, entro due mesi dopo impianto di LVAD). I pazienti TAVI sono stati confrontati con 80 pazienti di pari caratteristiche che nello stesso periodo giungevano in riabilitazione dopo sostituzione valvolare aortica per via tradizionale (sAVR); i pazienti LVAD sono stati confrontati con 47 pazienti di pari età affetti da scompenso cardiaco cronico (CHF) che giungevano nello stesso periodo dopo una riacutizzazione di scompenso. Nella coorte dei LVAD è stata inoltre valutata la funzione autonomica mediante lo studio dell’ heart rate variability. Per valutare gli effetti di una depressione della frazione d’eiezione del ventricolo sinistro (LVEF) sul processo riabilitativo, i pazienti AMI sono stati divisi in 2 gruppi in base alla LVEF (cut-off 40%). Inoltre, in 326 pazienti, è stata ottenuta una caratterizzazione glumetabolica mediante una curva da carico di glucosio standard (OGTT) somministrata ai soggetti senza diabete noto. Tutti i pazienti sono stati sottoposti ad un ciclo di ricondizionamento fisico con esercizi prevalentemente aerobici, distribuiti in 3 sessioni quotidiane per 6 giorni alla settimana (30 minuti di ginnastica respiratoria, seguiti da una sessione sulla cyclette, o su un arm-ergometro in coloro che non erano in grado di pedalare, nel pomeriggio 30 minuti di esercizi callistenici), sotto stretto monitoraggio telemetrico e diretta supervisione medica e fisioterapica. La capacità funzionale è stata valutata mediante six min walking test (6MWT) all’ingresso e alla dimissione e un test cardiopolmonare (CPET). Nelle coorti TAVI e LVAD è stata usata la scala di Barthel (Barthel Index, BI) per valutare il grado di autonomia. Nei pazienti AMI è stato registrato al follow up (fino a 5 anni, mediana 2 anni) l’incidenza di morte, nuove ospedalizzazioni, cessazione del fumo, attività fisica ed aderenza alla terapia. Risultati: Nonostante l’alto profilo di rischio della popolazione, il tasso di abbandono dal programma è risultato piuttosto basso (nell’ 1.3% dei pazienti TAVI, 1.1% degli AMI e 11.9% dei LVAD si è reso necessario il trasferimento all’ospedale per acuti per complicazioni non fatali). Tutti i soggetti che hanno completato il programma hanno migliorato la propria indipendenza, mobilità e capacità funzionale (incremento medio del BI 9.9±12.6, p<0.01 e 11.9±10.5, p<0.01, nei pazienti TAVI e LVAD rispettivamente; guadagno medio al 6MWT 60.4±46.4 mt, p<0.01, 83.2±36.0 mt, p<0.05, 70.7±55.7 mt, p<0.01, nei pazienti TAVI, LVAD and AMI, rispettivamente). Analizzando le specifiche coorti, una percentuale più bassa di pazienti TAVI rispetto a quelli del gruppo sAVR sono stati in grado di completare almeno un 6MWT (82% vs 92%) o un CPET (61% vs 95%) ma, in coloro che vi sono riusciti, non vi erano differenze significative tra i due gruppi in termini di distanza percorsa al 6MWT alla dimissione (272.7±108 vs 294.2±101 mt, p=0.42) e capacità funzionale al CPET (VO2 al picco 12.5±3.6 vs 13.9±2.7 ml/kg/min, p=0.16). Al termine del programma la performance fisica nei pazienti LVAD era generalmente scarsa, ma non dissimile da quella dei pazienti CHF (VO2 al picco al CPET 12.5±3.0 vs 13.6±2.9 ml/kg/min, p=0.20). Tra i pazienti AMI, coloro con LVEF<40% hanno raggiunto al CPET un VO2 al picco dell’esercizio significativamente più basso rispetto ai controlli (15.2±3.9 vs 18.2±5.2 ml/kg/min, p<0.01). Dopo somministrazione dell’OGTT è stata riscontrata un’alta prevalenza di alterazioni del metabolismo glucidico non precedente note (54%). Come atteso la capacità fisica era inferiore nei diabetici e nei prediabetici in confronto ai normoglicemici (al CPET VO2 al picco 15.3±4.1 vs 17.9±4.8 vs 19.4±5.5 ml/kg/min, p<0.01). Al follow up 73% dei soggetti hanno riferito di svolgere un’attività fisica regolare, 77% dei fumatori hanno definitivamente smesso ed è stata registrata un’alta aderenza alla terapia. La mortalità cardiaca e per tutte le cause è risultata 5.0% e 8.0% ad 1 anno, 8.0% e 13.0% a 5 anni, rispettivamente, ed è risultata più elevata nei soggetti più anziani ed in quelli con ridotta LVEF. Conclusioni: I pazienti che sono andati incontro ad intervento di TAVI e LVAD sono caratterizzati da un notevole grado di decondizionamento fisico. In tale prospettiva non si può automaticamente raggiungere un beneficio con il solo intervento ad alta tecnologia o con il trattamento farmacologico. Un breve periodo di RC, con supervisione medica, si è dimostrato fattibile, sicuro ed efficace in pazienti anziani dopo TAVI, così come dopo chirurgia aortica tradizionale, e dopo impianto di LVAD. Un programma precoce di RC aumenta l’indipendenza, la mobilità e la capacità funzionale ed andrebbe sicuramente incoraggiato in questi soggetti. Una RC intensiva e precoce basata sull’attività fisica e sul counselling è risultata sicura ed efficace anche in soggetti ad alto rischio dopo AMI, sia nel breve che nel lungo termine. Infatti è stato raggiunto un significativo miglioramento della capacità funzionale nel breve periodo - indipendentemente dalla funzione ventricolare sinistra residua o dallo stato glucometabolico - ed un’elevata aderenza alla terapia e alle modifiche dello stile di vita proposte. Nonostante l’elevato profilo di rischio di tali pazienti, questo può aver prodotto un effetto favorevole sulla mortalità.

This thesis details the measurement and simulation of patient skin doses arising from X-ray exposure during interventional cardiology procedures. Interventional cardiology procedures can be long and complex resulting in high skin doses, to the extent that radiation burns may be produced. Twenty patients were used in the study consisting of 10 coronary angiogram and 10 coronary angioplasty procedures. Radiochromic films were used to measure skin dose directly. The Gafchromic® XR-RV2 film was chosen for its suitability for this project. The key characteristics of this film were experimentally determined including: dose response, energy dependence, polarisation and post-exposure growth. The dose range was found to be ideally suited for the doses encountered in this study. Energy dependence was found to be ~14% between 60 and 125 kVp at 1 Gy and introduced an unavoidable uncertainty into dose calculations from unknown beam energies. Document scanner characteristics were also been investigated and a scanning protocol is determined. A mathematical model was created to use the geometry and exposure information encoded into acquisition files to reconstruct dose and dose distributions. The model requires a set of study files encoded according to the DICOM format, as well as user input for fluoroscopic estimations. The output is a dose map and dose summary. Simulation parameters were varied and results compared with film measurements to provide the most accurate model. From the data collected the relation between dose area product, maximum skin dose and fluoroscopic time were also investigated. The results demonstrated that a model based on acquisition information can accurately predict maximum skin dose and provide useful geometrical information. The model is currently being developed into a standalone program for use by the Medical Physics and Bioengineering department.

Background: The dental health of paediatric cardiology patients has been shown to be poorer than that of healthy children. Multiple factors could be implicated with dental anxiety potentially playing a major role. However, there is no published research specifically looking at dental anxiety amongst paediatric cardiology patients. Aims: The primary aim was to determine whether there was a difference in the level of dental anxiety between paediatric cardiology patients and a group of healthy children. The secondary aim was to establish whether dental anxiety was affected by previous medical history as measured by number of overnight hospital admissions, number of general anaesthetics and cardiac complexity category. Materials and Methods: Fifty-four participants were recruited into the study group from the outpatient cardiology clinic at Leeds General Infirmary. The control group comprised 53 children who attended consultant-led new patient orthodontic clinics. All participants were aged 8-16 years old. The children completed the Modified Child Dental Anxiety Scale (faces version) and their parents completed the Modified Dental Anxiety Scale along with a questionnaire regarding their child‟s medical and dental histories. Results: The mean level of dental anxiety was significantly higher in the study group (p<0.05). Other significant findings between the two groups related to socio-economic status, exodontia experience, overnight hospital admissions and general anaesthetic history. Analysis of covariance indicated that only the admission history might have had an effect upon child dental anxiety in this study. Conclusion: Paediatric cardiology patients had significantly increased levels of dental anxiety. It is likely that aspects of their medical history, notably overnight hospital admissions, are moderating factors but due to the multifactorial aetiology of dental anxiety, further research is required in order to identify specific factors involved.

Health-care delivery involves clinical handover processes that occur at many levels of inpatient care. These processes are essential to an effective health-care system due to their role in achieving efficient communication, reducing transmission time, and lowering costs. Ensuring safe and effective handover requires the coordination of multiple care providers that work together to deliver patient care efficiently. Poor coordination during handover can have major effects on patient care, leading to loss of information and contributing to adverse events. As health-care delivery evolves to become more patient-centered, handovers from short- to long-term care need to maintain a strong communication, which in turn will depend on the evolution of support systems for that communication. Due to the wide range of care providers and patient needs, there has so far been a lack of research work on handover processes. This study aims to explore the clinical handover process for patients moving from a cardiology unit to home and community care settings, and how they are affected by varying degrees of communication. It relies on literature review and a case study conducted at Montfort Hospital, Ontario, to identify and analyze the major factors involved in this type of handover, and to form suggestions about how this process could be improved. This thesis analyzes process scenarios arising in the case study, modeling them using business process management (BPM) tools and techniques to identify problems and formulate solutions. A model of the existing process is created and analyzed using business process management notation (BPMN), and is then subjected to analysis, the results of which identify several communication issues with a potential to cause delays and information loss. The findings highlight the importance of collaboration among care providers, and indicate the potential uses of BPM methodology to choreograph that collaboration. The study ultimately shows how improvements to collaboration and information exchange can increase the communication effectiveness in handover processes and reduce the probability of adverse patient events.

This thesis examines the potential applications of stroke distance measurement in clinical cardiology. Stroke distance is the linear analogue of stroke volume, measured by non-imaging Doppler ultrasound. Using magnetic resonance imaging, I have re-examined the relationships between linear and volumetric variables, also those between absolute and fractional volumetric measurements. Stroke distance appears to be moderately well correlated with stroke volume index and is also related to left ventricular ejection fraction. The degree of agreement between stroke distance and ejection fraction is similar to that between ejection fraction and stroke volume index. The role of stroke distance measurement within the coronary care unit is considered. The prognostic power of this variable in patients with myocardial infarction is described, and compared with published data for ejection fraction: Stroke distance is at least as good as ejection fraction in this respect, and is able to stratify mortality risk from zero to 29% at year. In addition, a low stroke distance value appears to be highly specific for a diagnosis of myocardial infarction in patients presenting with chest pain. The relationship between reperfusion after myocardial infarction and left ventricular function (stroke distance) at presentation is studied; subjects with electrocardiographic evidence or reperfusion occurring before admission to hospital had significantly better left ventricular function. Pre-hospital thrombolysis was associated with improved left ventricular function, in addition to a mortality benefit. The relationship between time to presentation and left ventricular function in myocardial infarction is also defined; greater left ventricular dysfunction is associated with earlier presentation. Stroke distance is compared with ejection fraction derived by radionuclide ventriculography as a predictor of the development of congestive heart failure. It appears to be at least the equal of ejection fraction as a predictor of cardiac death, or the development of cardiac failure. The role of stroke distance measurement during physiological stress is explored as a means of diagnosing myocardial ischaemia.

ABSTRACT Cardiovascular magnetic resonance (CMR) is a non-invasive imaging technique with increasing use and demand worldwide both in the clinical and research arenas. Its strength is accurate quantification of cardiac structure and function, and unique abilities with tissue characterisation. The most common indications for CMR in general include the assessment of ischaemia and viability, and cardiomyopathy. This thesis explores the application of CMR in the assessment of cardiovascular disease in two distinct but uncommon populations encompassed in these categories – chronic social cocaine users and patients with Fabry disease, chosen because of the unique diagnostic challenges related to each, and persistent difficulties risk stratifying and targeting treatment in these settings. Chapter 1 provides an introduction with a literature review of the common and important clinical and research applications of CMR, as well as a detailed review of the cardiovascular effects of cocaine use and Fabry disease. It also states the overarching hypotheses and aim of this thesis. Chapter 2 outlines the general CMR methodologies utilised in the studies encompassed in this thesis. Chapter 3 reports the harmful cardiovascular effects of chronic social cocaine use in otherwise healthy young individual with the aid of CMR, including increases in systolic blood pressure, myocardial mass, and aortic stiffness, but no evidence of previous silent myocardial infarctions. Given precise measurements of left ventricular mass (LVM) are important both clinically and from a research perspective, Chapter 4 addresses the methods of quantifying myocardial mass in hypertrophied hearts by either including or excluding the left ventricular papillary muscles (LVPM) in the total mass. This pilot study includes male patients with Fabry disease and left ventricular hypertrophy (LVH) and shows that the LVPM are critical to total LVM quantification. To follow on from this, Chapter 5 explores the same concept but applied to a diverse range of patient cohorts with LVH. It shows that there is disproportionate hypertrophy of the LVPMs in Fabry disease with and without LVH. It also provides further insight into the disease biology in Fabry disease by characterising the papillary muscles with T1 mapping. Chapter 6 explores the utility of CMR in identifying cardiac involvement in patients with Fabry disease, and how it can potentially affect management by reclassifying patients and allowing consideration of targeted therapy. Finally, Chapter 7 uses a combination of CMR parametric mapping techniques and serum biomarkers to show that cardiac involvement of Fabry disease with late gadolinium enhancement is a chronic inflammatory cardiomyopathy. These findings offer potential for therapeutic targets and management guidance.

This thesis investigates the diagnostic value of cardiac positron emission tomography when compared to single photon emission computed tomography for detection of coronary artery disease. This prospective study involves comparison of myocardial perfusion single photon emission computed tomography with coronary calcium scores; optimization of nuclear cardiac protocols in cardiac phantom experiments; and determination of diagnostic performance of cardiac positron emission tomography in the evaluation of myocardial viability in patients with significant coronary disease.

O objetivo desta pesquisa foi elaborar um glossário português-inglês de termos compostos em cardiologia, com o auxílio de ferramentas eletrônicas de processamento de corpus baseadas em tecnologia de orientação automática. A motivação surgiu da verificação da escassez de material de consulta para tradutores e intérpretes na área médica em língua portuguesa e também da grande freqüência de ocorrência de termos compostos em medicina. O corpus desta pesquisa consistiu em vários artigos de uma revista científica mensal bilíngüe escritos originalmente em português por cardiologistas e traduzidos para o inglês pela pesquisadora, perfazendo um total de 21.872 palavras. Diferentes critérios de identificação de compostos foram utilizados, gerando uma lista em ordem alfabética com 271 termos, aos quais foram acrescentadas as traduções que constam dos textos publicados na revista acima referida. Daí resultou o glossário português-inglês com 271 termos compostos em cardiologia. A pesquisadora tece considerações sobre terminologia, disciplina que fundamentou a pesquisa, e sua relação com a tradução.
This research aimed at developing a Portuguese-English glossary of compound terms in cardiology with the aid of electronic tools for corpus processing based on automation technology. The scarcity of reference material available for translators and interpreters in the medical area in Portuguese and the great frequency of occurrence of compound terms in the medical language motivated this research. The 21,872-word corpus consisted of several articles published in a monthly bilingual Brazilian scientific periodical, which is originally written in Portuguese by cardiologists and translated into English by the researcher. Different criteria were used for selecting the compound terms, yielding a 271-compound list in alphabetical order. Each term's corresponding English translation published in the scientific magazine was added to the list. The result was a Portuguese-English glossary with 271 compound terms in cardiology. Considerations on terminology, which served as basis for the research, and its relation to translation are provided.

L'intervention coronarienne percutanée (ICP) est réalisée en utilisant l'imagerie radiographique en temps réel dans une suite interventionnelle. La modélisation de ces procédures ICP pour aider le praticien implique la compréhension des différentes phases de la procédure ICP, par la machine d’intervention, qui peut être utilisées pour optimiser la dose de rayons X et l'agent de contraste. Pour atteindre cet objectif, l’une des tâches importantes consiste à segmenter différents outils d’intervention dans les flux d’images fluoroscopiques et à en déduire des informations sémantiques. L’arbre des composants, un puissant outil morphologique mathématique, constitue la base des méthodes de segmentation proposées. Nous présentons ce travail en deux parties: 1) la segmentation du cathéter vide à faible contraste, et 2) la segmentation de la pointe du guide et le suivi de la détection du vaisseau d’intervention. Nous présentons une nouvelle méthode de segmentation basée sur l’espace à plusieurs échelles pour détecter des objets faiblement contrastés comme un cathéter vide. Pour la dernière partie, nous présentons la segmentation de la pointe du guide avec le filtrage basé sur l’arbre de composants et proposons un algorithme pour suivre sémantiquement la pointe segmentée pour déterminer le vaisseau d’intervention
Percutaneous coronary intervention (PCI) is performed using real-time radiographic imaging in an interventional suite. Modeling these ICP procedures to help the practitioner involves understanding the different phases of the ICP procedure, by the interventional machine, which can be used to optimize the X-ray dose and the contrast agent. One of the important tasks in achieving this goal is to segment different interventional tools into the flow of fluoroscopic images and to derive semantic information from them. The component tree, a powerful mathematical morphological tool, forms the basis of the proposed segmentation methods. We present this work in two parts: 1) the segmentation of the low-contrast empty catheter, and 2) the segmentation of the tip of the guide and the monitoring of the detection of the intervention vessel. We present a new multi-scale space-based segmentation method for detecting low-contrast objects such as an empty catheter. For the last part, we present the segmentation of the tip of the guide with filtering based on the component tree and propose an algorithm to semantically follow the segmented tip to determine the intervention vessel

Includes abstract.
Includes bibliographical references (p.127-140).
Tuberculous (TB) pericarditis is associated with a mortality rate of 17-40% despite treatment with anti-tuberculosis drugs. The complications of TB pericarditis that confer mortality and morbidity are pericardial tamponade, effusive constrictive pericarditis, and constrictive pericarditis. Whilst the diagnosis and treatment of pericardial tamponade and constriction are well established, there is a paucity of evidence on the frequency and significance of tuberculous effusive constrictive pericarditis. The primary purpose of this work was to determine the prevalence, predictors, fractal (geometric) structure, biomarker signature, and outcome of effusive constrictive TB pericarditis.

Background: Little is known about the mechanisms, clinical characteristics, natural history and outcomes of cardiomyopathy amongst Africans. Familial aggregation of cardiomyopathy has not been studied systematically in an African setting. Further, it is not clear whether the various phenotypic expressions of cardiomyopathy represent disparate clinical entities, or whether they are merely different forms of the same disease manifested differently in different circumstances. Methods: Two cohorts of patients with cardiomyopathy were utilised for this study: (1) patients with cardiomyopathy seen at the specialist cardiomyopathy clinic at Groote Schuur Hospital, Cape Town between February 1, 1996 and December 31, 2009; and (2) a group of hypertrophic cardiomyopathy (HCM) patients and first degree relatives seen in a specialist cardiogenetic clinic at Tygerberg Hospital, who underwent cardiovascular magnetic resonance (CMR) imaging at Groote Schuur Hospital.

Background and hypothesis: Standard pharmacological treatment for heart failure improves cardiac remodelling and survival in the setting of chronic heart failure, but is suboptimal in cases of acute heart failure (AHF). Peripartum cardiomyopathy (PPCM), de-novo hypotension (often due to haemorrhagic shock), and Takotsubo cardiomyopathy (TC) are conditions which have acute onset of heart failure, and often present with high mortality rates. In patients treated for these pathologies, a variation in the heart rate is observed and could potentially be used as a target to improve the treatment of AHF. We therefore questioned whether the use of a sinoatrial node inhibitor (ivabradine) to modulate heart rate may improve outcomes in AHF. Objectives and methods: Our objectives were 3-fold: (1) to explore the effect of a standard treatment strategy on heart rate in a South African cohort of PPCM patients after 6 and 12 months follow-up. (2) To explore the effect of ivabradine, a sinoatrial node inhibitor in an established signal transducer and activator of transcription 3 (STAT3) knockout mouse model of PPCM (with 3 consecutive pregnancies). Mice were fed ivabradine for 30 days (10mg/kg/day in drinking water), following the 3rd weaning. Trans-thoracic echocardiograms (TTE) were done at the end of the 3rd weaning, and after 30 days of treatment with ivabradine. Hearts were harvested after the second TTE for histology staining and messenger ribonucleic acid (mRNA) quantitation of transcripts involved in heart failure. (3) To explore the role of the sinoatrial node inhibitor in an ex-vivo model of de-novo AHF due to hypotension, and a newly developed ex-vivo model of TC. In the AHF model, hearts were stabilised before administering Ivabradine (3μM) in a buffer containing high free fatty-acids at a low pressure (to mimic hypotension/ haemorrhage shock conditions). A pressure- sensing balloon in the left ventricle measured heart rate, diastolic and systolic pressure, left ventricular developed pressure, rate pressure products and functional recovery. In the TC model, hearts were stabilised, then given a buffer with high free fatty-acid content and 10 times a physiological dose of adrenaline to mimic the adrenergic response seen in TC. Thereafter, hearts were restored to stabilisation pressure and substrate for recovery. Results: (1) Clinical outcomes indicated that patients on maximum standard therapy improved symptomatically and on the New York Heart Association scale. However, heart rates of PPCM patients remained elevated after 6 months of treatment. (2) In PPCM mice, a treatment with ivabradine was associated with reduced fibrotic infiltration in cardiac tissue and with a decrease in levels of atrial natriuretic peptide and Fibronectin mRNAs. (3) Both hypotensive AHF and TC models showed a tendency toward better cardiac function with ivabradine at the end of the acute phases. This advantage was lost after withdrawal of ivabradine during recovery. Conclusion: In South African women with PPCM treated with standard therapy, heart rate remains elevated, therefore suggesting that these women may benefit from the use of ivabradine as an additional therapy, particularly in patients who may be intolerant to β-blockers. The long-term use of ivabradine in the setting of cardiac dysfunction appears to have beneficial effects on remodelling, as treatment with ivabradine in our mouse PPCM model showed reduced cardiac fibrosis. The ex-vivo models of hypotensive AHF and TC both showed benefit in reducing heart rate during the acute phases, and hold the potential of being an intervention therapy to improve the outcome in patients who are brought to hospital while still in the acute phase.

The pleiotropic cytokine tumour necrosis factor alpha (TNFα) is produced by the heart in response to the ischaemic preconditioning (PC) stimulus. We hypothesised that this endogenously produced peptide may play a role in activating the ischaemic PC mediated tolerance towards a subsequent ischaemic insult in muscle cells. To test this and to delineate the downstream signalling cascades mediating this programme we developed classic PC protocols in adherent mature murine C2C12 myotubes and in human cardiac derived Girardi cell lines. The C2C12 myotubes were preconditioned using either one hour of simulated ischaemia (SI) or the PC-mimetic adenosine (0.1 mM) or TNFα (0.5 ng/ml) followed by one hour of reoxygenation followed by an eight hour SI insult. Cell viability was assessed by measuring lactate dehydrogenase (LOH) release. Simulated ischaemia (SI), PC, adenosine and TNFα activated the PC programme and increased cell viability by 40±3%, 28±5% and 36±4% respectively compared to the SI controls (p<0.005 in all experiments, n≥4 x 6 well plates in all groups). Cell viability was also evaluated by the measurement of propidium iodide uptake on flow cytometry. Preconditioning and TNFα enhanced cell viability with a reduction in propidium iodide uptake by 28% and 41 % respectively versus the ischaemic controls. To evaluate whether TNFα activation of the nuclear regulatory protein nuclear factor kappa B (NFₖ B) mediates this myocyte protection, the NFₖ B antagonists diethyldithiocarbamate (DDTC 10mM) or sodium salicylate (SA 100μM) were co-administered with TNFα. The myocyte protective effect of TNF a was significantly decrease with both antagonists, although not completely inhibited/blocked (DDTC - attenuated cell viability by 62 ±6% and SA by 45 ±5% compared to the TNFα preconditioned cells (p <0.05 vs SI controls and p<0.05 vs TNFα PC, with either antagonists). To confirm these data, TNFα was used as a PC-mimetic in the isolated Langendorff perfused rat heart (Langendorff) preparation. Infarct size was used as the end point. In parallel with cell culture studies, TNFα again conferred preconditioning induced cardioprotection with partial abrogation of these effects with the pharmacological antagonists of NFₖ B. Thus, TNFα administration mimics the cytoprotective effects of ischaemic PC in cardiac, skeletal myocytes and in the isolated perfused rat heart. Moreover, these data support the role of TNFα production as an endogenous paracrine / autocrine signalling peptide which promotes myocyte cellular survival, in part, through activation of NFₖ B.

High density lipoprotein cholesterol (HDL) and its component sphingosine-1-phosphate (S1P) protect against myocardial infarction. Recently, the SAFE (survivor activating factor enhancement) pathway, involving tumour necrosis factor (TNF) and the transcription factor signal transducer and activator of transcription 3 (STAT-3), has been identified as a key signalling pathway in cardioprotection, although the end effector remains unclear.

Includes bibliographical references (leaves 52-56).
The expanding application of cardiac resynchronization (CRT) and implantable cardioverter-defibrillator therapy (lCD) to include patients with congenital heart disease requires careful evaluation of selection criteria and unconventional adaptive strategies to ensure clinical efficacy. A single centre prospective analysis of adults post atrial redirection surgery (Mustard operation) for dextro-transposition of the great arteries (d-TGA) presenting with systemic right ventricular (sRV) dysfunction and at risk of sudden cardiac death (SCD). All patients ( mean age 25 years, range 18-35) with varying functional disability{New York Heart Association (NYHA) II-III} receiving ICDs ± concomitant CRT were evaluated. Total follow-up period was 24 months. A patient individualized approach was used for device implantation. Endocardial, epicardial and transthoracic defibrillation strategies were examined in 5 consecutive cases. A hybridized form of CRT was employed in two patients. Only one patient demonstrated response to therapy while the other deteriorated during biventricular pacing (BVP). This prompted a novel approach to CRT using noncontact mapping (NCM) and acute intra-arterial blood pressure response to guide endocardialsRV lead placement in a single patient. The ejection fraction increased from 23 -33% within 1week post procedure and clinical improvement was sustained after 6-months follow-up. Application of CRT II CD therapy to patients with sRV dysfunction requires individualized and adaptive strategies to overcome anatomical constraints. This study represents a chronological and evolutionary account of these measures.

Includes bibliographical references.
The treatment and outcome myocardial infarction has been revolutionised by the demonstration that thrombolytic grugs can open the infarct-related arterty, salvage ischaemic myocardium, preserve left ventricular function and save lives. However, thrombolytic drugs are not uniformly effective in securing or maintaining patency of the infarct-related artery.

Tuberculosis is the most common cause of pericarditis in Africa. The dual human immunodeficiency virus (HIV)-tuberculosis epidemics are major contributors to the burden of extra-pulmonary tuberculosis, including tuberculous pericarditis. Mortality rates remain unacceptably high. Atrial fibrillation (AF) is the most common sustained arrhythmia encountered in clinical practice. It is associated with increased cardiovascular mortality and morbidity, as well as complications related to thromboembolic disease and haemodynamic instability. Similarly, atrial flutter (AFL) is a common macro-reentry arrhythmia, often associated with AF and its complications. While there is a recognized association between atrial fibrillation and / or atrial flutter (AF/AFL) and tuberculous pericarditis, there are limited data regarding the prevalence, determinants, natural history, and outcomes of AF/AFL in tuberculous pericarditis. Hypothesis: In patients with tuberculous pericarditis, AF/AFL is common, and when compared to tuberculous pericarditis patients that are in sinus rhythm, is associated with increased morbidity and mortality. Aims In participants with tuberculous pericarditis enrolled into the Investigation of the Management of Pericarditis (IMPI) trial, we intend to: 1. Estimate the prevalence of AF/AFL 2. Describe the natural history of AF/AFL 3. Identify clinical, biochemical and, echocardiographic predictors of AF/AFL 4. Determine the clinical impact of AF/AFL.

In the light of studies which show the upregulation of VEGF in contractile cells subjected to cyclic stretch and the profound effects which cyclic stretch has been shown to have on the release of other cytokines by SMC, this study investigates the role which cyclic stretch might play in VEGF expression by SMC in a compliant environment. Furthermore, following observations of receptor phosphorylation in response to cyclic stretch in vascular cells, the effect of cyclic strain on the KDR-mediated endothelial response to locally-released VEGF was also investigated. Low passage number bovine aortic SMC and EC were plated on collagen-coated elastomer plates and subjected to 10% repetitive strain at 1 Hz. The mRNA expression of VEGF in SMC and the phosphorylation of KDR on EC were determined by northern blotting and western blotting respectively. The biological activity on EC and levels of VEGF secreted into the medium by SMC under cyclic stretch were investigated using a migration assay and ELISA respectively. Cyclic stretch was found to cause a 3.3 (±1.5 p < 0.005) fold increase in VEGF mRNA levels over unstretched controls at 4 hours. This biomechanically-induced expression was found to drop slightly by 24 hours and to be approximately equivalent to expression induced by the cytokine bFGF over the same time course. These results correlated with an increase in VEGF levels in media from stretched SMC capable of inducing migration of EC by 1.6 fold although additional EC chemotactic factors appear to be released by stretch. Furthermore, although the levels of KDR remained constant under cyclic stretch, average KDR phosphorylation was found to increase weakly over time due to cyclic stretch. These results show that cyclic stretch affects the VEGF communication between SMC and EC at both the level of VEGF expression by SMC and at the level of VEGF recognition by the KDR receptor on EC. It is possible that through the nitric oxide (NO) pathway, VEGF release may alleviate abnormally high levels of cyclic strain. It is hoped that a better understanding of the role of VEGF communication between stretched SMC and EC will enable the design of a graft in which the level of compliance encourages SMC to maintain a functional endothelium. Following this it is hoped that the low levels of SMC and pericytes invading the graft, pacified by endothelial cell mediation, will not result in intimal hyperplasia but rather play a role in microvessel maintenance and more complete healing.

Includes abstract.
Includes bibliographical references.
Tachycardia-induced cardiomyopathy (TIC) is a reversible cause of LV systolic dysfunction that can complicate any supraventricular or ventricular tachyarrhythmia. This study is the first to compare features of pure and impure TIC. We found that impure TIC may develop more quickly than pure TIC, as impure TIC patients have a shorter duration and more severe symptoms at presentation, which suggests that underlying structural heart disease is a risk factor in the pathogenesis of TIC.

Includes bibliographical references (leaves 147-180).
Chronic valvular heart disease is characterised by compensatory mechanisms that result in a long asymptomatic phase associated with variable disease progression. After the development of symptoms or left ventricular dysfunction, mortality is high without surgical intervention. Currently there is no known medical therapy that influences disease progression or clinical outcome. While the development of symptoms or left ventricular dysfunction are the cardinal indications for valve surgery, routine echocardiography may not detect early left ventricular dysfunction and the development of early symptoms may not be appreciated. Numerous studies demonstrate that increased natriuretic peptide plasma levels, including atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP) and amino-terminal BNP (N-BNP) reflect left ventricular dysfunction, correlate with symptoms of cardiac failure and are independent prognostic markers for clinical outcomes in diverse cardiac conditions, but very few studies address natriuretic peptides in patients with valvular heart disease. The aims of this thesis are firstly, to determine the clinical utility of measuring natriuretic peptide plasma levels in patients with valvular heart disease, and secondly, to provide supportive biochemical evidence to established histological evidence that aortic stenosis is an inflammatory disease. One hundred and sixty three patients with chronic valvular heart disease, including aortic stenosis (n=74), aortic regurgitation (n=40) and mitral regurgitation (n=49) underwent independent assessment of symptoms, transthoracic echocardiography and measurement of plasma levels of ANP, BNP and N-BNP. Natriuretic peptide levels were significantly higher in symptomatic compared with asymptomatic patients after adjustment for echocardiographic measures of disease severity and left ventricular function. Of 29 asymptomatic patients with aortic stenosis followed for a mean of 18 months, patients with an N-BNF level above the normal range or with a greater increase in N-BNP/year were at increased risk of symptomatic deterioration. In 33 patients with aortic stenosis who underwent aortic valve replacement, N-BNP levels decreased and symptoms consistently improved by 6 months postoperatively in patients with a preoperative N-BNP level above the normal range, but N-BNP levels did not decrease and symptoms less reliably improved in patients with a preoperative N-BNP level within normal limits. In contrast to the established theory that aortic stenosis is a degenerative process not amenable to medical therapy, recent histological studies suggest that aortic stenosis may be an inflammatory disease with similarities to coronary atherosclerosis. To further address this issue, high sensitivity C-reactive protein (CRP) was measured in 20 patients with non-rheumatic aortic stenosis, 19 patients with non-rheumatic aortic regurgitation and 31 healthy controls, as well as 6 months after valve replacement in aortic stenosis. CRP was significantly increased in aortic stenosis, but not aortic regurgitation compared with controls and decreased after valve replacement in aortic stenosis. These observations are consistent with histological evidence that the aortic valve is the site of active inflammation. In conclusion, measurement of plasma natriuretic peptide levels complement clinical and echocardiographic evaluation of patients with valvular heart disease and may assist with the timing of valve surgery. Novel evidence that aortic stenosis may be an inflammatory disease is presented and suggests further studies are required to determine whether agents with anti-inflammatory actions may have a role in delaying disease progression. Following on the studies presented in this thesis, a large multicentre study has commenced in New Zealand to confirm these findings that has the potential to change clinical practice.

Background: Atrial fibrillation (AF) is the most common arrhythmia and may be complicated by embolic stroke. It is also associated with a significant risk of heart failure and mortality. The burden of rheumatic heart disease remains great in the developing world. The prevalence of AF in those with rheumatic heart disease is in the order of 20% with a resultant 17-fold increased risk of embolic stroke. Over time, many other risk factors for stroke in the AF population have been described. Stroke risk stratification tools such as the CHADS₂ (Congestive heart failure, hypertension, age of 75 or older, diabetes mellitus or stroke/TIA) and CHA₂DS₂VASc (with the addition of a second age category, female gender, and peripheral artery disease) scores have been developed. These are used to assess the need for anticoagulation and have been well validated. These scores have traditionally excluded those patients with valvular AF. Valvular AF has not been studied extensively in the contemporary era. Oral anticoagulation had previously been advised in all patients with valvular AF. Little is known however about outcomes for stroke and mortality in this cohort of patients. Furthermore, the utilization of the CHADS₂ and CHA₂DS₂VASc scores may provide incremental benefit in prognostication and resultantly, both more diligent prescription of anticoagulation and improved outcomes. Objectives: The objectives of this study were as follows - 1. To determine the prevalence of AF in the Global Rheumatic Heart Disease Registry (the REMEDY study) and in the Groote Schuur Hospital (GSH) cohort. 2. To assess the demographic, social and clinical characteristics of patients with AF in the REMEDY study and in the GSH cohort. 3. To assess the frequency of CHADS₂ and CHA₂DS₂VASc risk factors in the GSH cohort and to calculate a CHADS₂ and CHA₂DS₂VASc score on each of the patients with AF. 4. To establish whether CHADS₂ and CHA₂DS₂VASc scores further increase the risk of stroke and death in this cohort of patients with valvular AF. Methods: This is a substudy of the Global Rheumatic Heart Disease Registry (the REMEDY study). We assessed those with AF from the entire cohort for prevalence and outcome data. Patients with ECG or Holter proven AF from the GSH cohort were further risk stratified using the CHADS₂ and CHA₂DS₂Vasc scores. Clinical data was obtained from folder reviews and telephonic interviews. The CHADS₂ and CHA₂DS₂Vasc scores for each patient in the GSH cohort were calculated. Patients were followed up for 2 years and information pertaining to death and stroke were obtained from folder reviews. These were then correlated with the CHADS₂ and CHA₂DS₂Vasc scores. Results: A total of 2624 REMEDY patients were analysed. Of these, 22% in the total cohort (586 of 2684 patients) and 38.2% in the GSH cohort (187 of 489 patients) had AF. These patients were older (35 years vs. 25 years, p<0.0001), more likely to be female (73.1% vs. 65.6%, p=0.001) and more frequently had a history of congestive heart disease (41.0% vs. 33.3%, p=0.001) when compared to those in sinus rhythm. They also had significantly more strokes (13.8% vs. 5%, p<0.0001) and a poorer NYHA class (NYHA III& IV 30.8% vs. 25.2%, p=0.002). The cohort with AF had more severely impaired left ventricular (LV) function compared to those in sinus rhythm (Ejection fraction (EF) 57% vs. 61%. P<0.0001). The presence of a larger left atrial (LA) size, spontaneous echo contrast and LA thrombus was much greater in the AF cohort. Of those patients in AF, only 68% had received a prescription for warfarin. The GSH cohort was risk stratified using the CHADS₂ and CHA₂DS₂VASc scores. Twenty-three percent of patients had a CHADS₂ score of 0 and 27.7% of 1. When the same cohort was scored using the CHA₂DS₂VASc score, only 5.4% had a score of 0; this difference was mainly driven by the additional category of female gender. The patients in our cohort were young (median age 28 years) and had few comorbidities. Despite this, patients with AF did significantly worse than those in sinus rhythm, with a stroke rate of 4.6% and a mortality rate of 13.1% observed at 2 years (compared to a 1.5% stroke rate and 5.5% mortality rate for those in sinus rhythm). The presence of any additional comorbidities significantly reduced survival in both the short and long term. Greater CHA₂DS₂VASc score categories (CHA₂DS₂VASc 1 and CHA₂DS₂VASc 2 or more) conferred an incrementally higher risk of death. Conclusion: In a contemporary cohort of patients with rheumatic heart disease, AF is common with a prevalence of 22-39%. These patients were older and exhibited features of more advanced disease both clinically and on echo, compared to their sinus rhythm counterparts. The mortality and stroke rates in the AF group were high despite the relatively young age of this cohort. Mortality and stroke increased significantly and incrementally with each greater CHA₂DS₂VASc score category. Given the differences in chronicity between RHD in the developed world (i.e., disease of older people) and RHD in developing countries (i.e., disease of the young), these results cannot be extrapolated to those living in the first world.

The International Commission of Radiological Protection (ICRP) advises that in principle Diagnostic Reference Levels (DRL) could be used in fluoroscopically guided interventional procedures to avoid unnecessary stochastic radiation risk. The increase in complexity of interventional procedures, combined with a lack of specialist training on radiation techniques, poses a significant risk to patients. These risks have not gone unnoticed by government authorities worldwide and in 2015 the South African Department of Health: Directorate Radiation Control issued requirements to license holders of interventional fluoroscopy units, requiring that a medical physicist optimize their radiation usage using DRLs. The Dose Area Product (DAP) quantity measured for each patient represents a dosimetry index, the value of which for the purpose of improvement should be optimized against the DRL. In this dissertation, I aim to establish if DRLs in the South African private healthcare interventional theatres are high compared to international levels and whether DRLs will optimize the doses used.

Strong evidence has been found to link the diagnosis of CHD with depression, and patients with all CHD-related diagnoses and co-morbid depression display higher morbidity and mortality from CHD than those individuals without depression. Screening and treatment of depression by cardiology clinicians continues to be limited due to poor symptom recognition and lack of desire to treat perceived primary care conditions in specialty practice. The American Heart Association has designated timely assessment and treatment/referral of depression as primary goals for high-quality evidenced-based cardiology care to improve patient outcomes in CHD.This study employed a quasi-experimental descriptive pretest-posttest study design for the purposes of (1) understanding diagnostic and treatment practices for depression in the presence of CHD by nurse practitioner and physician cardiology providers (n=35) in a large metropolitan private outpatient cardiology practice and; (2) adaptation of a valid and reliable depression screening tool (Patient Health Questionnaire-9) to an existing electronic medical record system for use in the sample practice.Findings from the study showed that even though all providers (100%) believed that depression inhibited patients' ability to make positive CHD risk-reducing lifestyle changes, and the majority (73.7%) felt that depression contributed to the progression of CHD, no formal screening for depression was being performed. Less than half (42.1%) of providers in the sample treated depression in their clinic practice, and the large majority (89.5%) referred patients back to primary providers for all depression care.Since 2008 guidelines for depression care by cardiology providers were recommended by the American Heart Association (endorsed by the American Psychiatric Association), it is questionable if these recommendations are filtering down to outpatient cardiology practice. Provider education to improve confidence with depression screening and treatment, and provision of concise easy-to-use care templates in outpatient EMR systems may help to improve compliance with recommendations while maximizing patient outcomes for depressed CHD patients.Advanced practice nurses have been consistently instrumental in the development and management of performance-enhancing processes that improve care quality and patient outcomes. As nursing practice leaders, nurse practitioners should be progressive in supporting implementation of best-practice for depression care in outpatient cardiology practice settings.

The sensitivity for observing physiological processes makes nuclear imaging an important tool in medical diagnostics. Different types of nuclear imaging modalities, with emphasis on the software components and image reconstructions, are presented in this thesis:  the Cardiotom for myocardial heart studies at the Karolinska University Hospital, the small animal Positron Emission Tomograph (PET) scanners for research and the SPECT, PET, spiral CT and Cardiotom demonstrators for the Royal Institute of Technology medical imaging laboratory. A modular and unified software platform has been developed for data representation, acquisition, visualization, reconstruction and presentation of the programs of the imaging devices mentioned above. The high performance 3D ML-EM and OS-EM iterative image reconstruction methods are implemented both on Cardiotom and miniPET scanners. As a result, the in-slice resolution of the first two prototypes of the Cardiotom today is the same as the formerly used filtered back-projection, however the in-depth resolution is considerably increased. Another improvement due to the new software is the shorter time that is required for data acquisition and image reconstruction. The new electronics with the newly developed software ensure images for medical diagnosis within 10 minutes from the start ofthe examination. The first system from the standardized production of the Cardiotom cameras is in the test phase. The performance parameters (sensitivity, spatial and energy resolution, coincidence time resolution) of the full ring mini PET camera are comparable to other small animal PETsystems.
QC20100721

Introduction Infective endocarditis is a microbial infection of the endothelial surface of the heart, predominantly the heart valves, that is associated with high mortality and morbidity. Few contemporary data exist regarding affected children in our context. Aims and Objectives: We aimed to describe the profile and treatment outcomes of infant and childhood endocarditis at our facilities. Methods: This is a retrospective review of infants and children with endocarditis at two public-sector hospitals in the Western Cape Province of South Africa over a 5-year period. Patients with “definite” and “possible” endocarditis according to Modified Duke Criteria were included in the review. Results: Forty-nine patients were identified for inclusion; 64% of patients met “definite” and 36% “possible” criteria. The in-hospital mortality rate was 20%; 53% of patients underwent surgery with a post-operative mortality rate of 7.7%. The median interval from diagnosis to surgery was 20 days (interquartile range 9-47 days). Valve replacement occurred in 28% and valve repair in 58%. There was a significant reduction in valvular dysfunction in patients undergoing surgery and only a marginal improvement in patients treated medically. Overall, 43% of patients had some degree of residual valvular dysfunction. Conclusion: Endocarditis is a serious disease with a high in-hospital mortality and presents challenges in making an accurate diagnosis. Despite a significant reduction in valvular dysfunction, a portion of patients had residual valvular dysfunction. Early surgery is associated with a lower mortality rate, but a higher rate of valve replacement when compared to delayed surgery.

Recombinant adeno-associated viral (rAAV) vectors, have been developed and are being clinically trialled for treatment of cardiovascular diseases. With an improved understanding of the molecular mechanisms involved in pacemaker dysfunction, gene therapy is being used to advance viable treatment options that can potentially replace the need for electronic devices. Currently, the only viable management option for pacemaker dysfunction is the insertion of an electronic pacemaker. We however proposed an alternative gene therapy approach using rAAV vectors to deliver the gene human T-box 18 (hTBX18), to advance the creation of a biological pacemaker. The work in this thesis aimed to address the limitations with current approaches to biological pacemaker development, to set up a relevant animal model to assess this gene transfer approach and to assess rAAV vector biosafety in this novel model. In the first phase of work, we successfully generated an original rAAV construct expressing hTBX18 and showed that rAAV6-hTBX18 gene transfer to ventricular cardiomyocytes resulted in molecular, physiological, morphological and functional changes, recapitulating the pacemaker phenotype in an in vitro setting. In the second body of work, we successfully developed, characterised and validated a large animal model of atrioventricular block that is stable and technically feasible in adult sheep. In the third body of work, we successfully performed rAAV cardiac infusions in sheep and analysed vector shedding in excreta samples from urine, nasal mucus, saliva and faeces. We concluded that rAAV-mediated gene transfer into sheep hearts results in low-grade shedding of non-functional vector particles following vector delivery. This thesis therefore lays the groundwork for the next phase of pre-clinical development of biological pacemakers using clinically relevant rAAV vectors in a previously non-existent sheep animal model.

Thesis (MBA (Business Management))--University of Stellenbosch, 2009.
ENGLISH ABSTRACT: South Africa is on the verge of major changes in the private medical sector. The government’s planned National Health Insurance has far reaching implications for all role players in the industry, as well as for the general public. This paper looks at the changes that have been made since the ANC government came to power in 1994 and then continues to look at possible models for the new National Health Insurance plan. A proposal on practicing cost-effective cardiology within this new system is made. The data of a pilot project between a private service provider and a managed healthcare company is analysed as a basis of this discussion.
AFRIKAANSE OPSOMMING: Suid-Afrika se mediese bedryf staan op die vooraand van groot veranderinge. Die regering se beplande Nasionale Gesondheidsplan het verreikende implikasies vir alle rolspelers in die bedryf, sowel as die algemene man op straat. Die dokument kyk oorsigtelik na die veranderinge wat ondergaan is sedert die ANC regering aan bewind gekom het in 1994 en gaan daarna voort om na moontlike opsies te kyk hoe die nuwe gesondheidsmodel daarna gaan uitsien. Voorstelle word gemaak oor hoe privaat kardiologie in die nuwe sisteem koste-effektief beoefen kan word. ‘n Lootsprojek van ‘n privaat diensverskaffer en ‘n bestuurde gesongheidsorg maatskappy se data word ontleed as basis vir die bespreking.

La dégénérescence valvulaire mitrale (MVD) est la cardiopathie la plus fréquente chez le chien de petit format. Certaines variables écho-Doppler et sanguines sont incontournables dans son évaluation mais nécessitent d'être interprétées selon un intervalle de référence (IR) spécifique. L'objectif de ce travail a été de déterminer des IR pour 31 variables d'utilité clinique en cardiologie vétérinaire dans une population importante de chiens sains de petit format et selon les recommandations du Clinical and Laboratory Standard Institute. Les trois études réalisées permettent de conclure que l'élaboration d'IR spécifiques dans une sous-population canine est pertinente pour certaines variables. De plus, l'effet de certains facteurs comme le poids, l'âge et le sexe doivent être pris en compte si un intérêt clinique est identifié
Degenerative mitral valve disease is the most common heart disease in small size dogs. Several echocardiographic, Doppler and blood variables are crucial in the assessment of the disease but need to be interpreted in the light of a specific reference interval (RI). The aim of this work was to determine RI for 31 variables of clinical interest in veterinary cardiology within a large population of healthy small size dogs by using the Clinical and Laboratory Standard Institute recommendations. The three studies performed here allowed to conclude that determination of specific RI in this canine sub-population is relevant. Moreover, the effect of covariates such as body-weight, age and gender should be taken into account only if a clinical interest is identified