Ng, Mei. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references (leaves xvi-xlviii). / Abstracts in English and Chinese. / ACKNOWLEDGEMENTS --- p.i / ABSTRACT / In English --- p.ii / In Chinese --- p.iv / LIST OF TABLES --- p.vi / LIST OF FIGURE --- p.viii / ABBREVIATIONS / For Units --- p.ix / For Prefixes of the International System of Units --- p.ix / For Terms Commonly Used --- p.X / Chapter CHAPTER 1 --- Overview of Childhood Obstructive Sleep Apnoea Syndrome (OSAS) / Chapter 1.1 --- Prevalence --- p.1 / Chapter 1.2 --- Clinical Features --- p.3 / Chapter 1.3 --- Definitions and Cutoffs --- p.4 / Chapter 1.4 --- Pathophysiology --- p.6 / Chapter 1.5 --- Risk Factors / Chapter 1.5.1 --- Gender --- p.8 / Chapter 1.5.2 --- Obesity --- p.9 / Chapter 1.5.3 --- Adenotonsillar Hypertrophy --- p.10 / Chapter 1.5.4 --- Genetic --- p.11 / Chapter 1.5.5 --- Atopic Diseases --- p.12 / Chapter 1.6 --- Complications / Chapter 1.6.1 --- Neurobehavioural Deficits --- p.13 / Chapter 1.6.2 --- Growth Defects --- p.14 / Chapter 1.6.3 --- Metabolic Disorders --- p.16 / Chapter 1.6.4 --- Systemic inflammation --- p.17 / Chapter 1.6.5 --- Cardiovascular Consequences --- p.19 / Chapter 1.7 --- Diagnosis --- p.20 / Chapter 1.8 --- Treatment / Chapter 1.8.1 --- Surgical Treatment --- p.22 / Chapter 1.8.2 --- Continuous Positive Airway Pressure (CPAP) --- p.24 / Chapter 1.8.3 --- Corticosteroids --- p.24 / Chapter 1.8.4 --- Leukotriene Receptor Antagonist --- p.25 / Chapter 1.8.5 --- Oral Appliances --- p.26 / Chapter 1.8.6 --- Weight Control --- p.27 / Chapter CHAPTER 2 --- OSAS and Cardiovascular Complications in Adults / Chapter 2.1 --- Mechanism / Chapter 2.1.1 --- Acute Cardiovascular Responses --- p.28 / Chapter 2.1.2 --- Chronic Cardiovascular Responses --- p.29 / Chapter 2.2 --- Hypertension / Chapter 2.2.1 --- Epidemiological and Clinical Data --- p.31 / Chapter 2.2.2 --- Characteristics --- p.32 / Chapter 2.2.3 --- Mechanisms --- p.33 / Chapter 2.2.4 --- Treatment --- p.34 / Chapter 2.3 --- Heart Failure --- p.35 / Chapter 2.4 --- Stroke --- p.37 / Chapter 2.5 --- Cardiac Arrhythmias --- p.39 / Chapter 2.6 --- Myocardial Ischemia and Vascular Disease --- p.41 / Chapter 2.7 --- Pulmonary Hypertension --- p.43 / Chapter CHAPTER 3 --- OSAS and cardiovascular complication in children / Chapter 3.1 --- Blood Pressure --- p.45 / Chapter 3.2 --- Ventricular Hypertrophy and Dysfunctions --- p.48 / Chapter 3.3 --- Heart Rate Variability --- p.50 / Chapter 3.4 --- Arterial Tone --- p.51 / Chapter 3.5 --- Endothelial Function --- p.51 / Chapter CHAPTER 4 --- Longitudinal follow-up study of children with OSAS - a cardiovascular perspective / Chapter 4.1 --- Introduction --- p.53 / Chapter 4.2 --- Methods / Chapter 4.2.1 --- Subjects and Study Design --- p.57 / Chapter 4.2.2 --- Polysomnography --- p.59 / Chapter 4.2.3 --- Ambulatory Blood Pressure Measurement --- p.61 / Chapter 4.2.4 --- Statistical Analysis --- p.62 / Chapter 4.3 --- Results / Chapter 4.3.1 --- Subject Characteristics --- p.64 / Chapter 4.3.2 --- Blood Pressure During Wakefulness --- p.71 / Chapter 4.3.3 --- Blood Pressure During Sleep --- p.76 / Chapter 4.3.4 --- Nocturnal Blood Pressure Dipping --- p.83 / Chapter 4.3.5 --- Blood Profile --- p.86 / Chapter 4.4 --- Discussion --- p.87 / Chapter 4.5 --- Conclusion --- p.99 / Reference List --- p.xvi

Au, Chun Ting. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2007. / Includes bibliographical references (leaves xxvii-lv). / Abstracts in English and Chinese. / ACKNOWLEDGEMENTS --- p.i / ABSTRACT / In English --- p.ii / In Chinese --- p.v / LIST OF TABLES --- p.vii / ABBREVIATIONS / For Units --- p.ix / For Prefixes of the international system of units --- p.ix / For Terms commonly used in the report --- p.x / STATEMENT OF WORK DONE --- p.xvi / Chapter CHAPTER 1 --- Overview of Childhood Obstructive Sleep Apnea Syndrome (OSAS) / Chapter 1.1. --- Clinical Features of Childhood OSAS --- p.1 / Chapter 1.2. --- Definition of Childhood OSAS --- p.2 / Chapter 1.3. --- Prevalence of Childhood OSAS --- p.3 / Chapter 1.4. --- Pathophysiology --- p.4 / Chapter 1.5. --- Risk Factors --- p.6 / Chapter 1.6. --- Diagnosis --- p.10 / Chapter 1.7. --- Treatment / Chapter 1.7.1. --- Tonsillectomy and Adenoidectomy (T&A) --- p.12 / Chapter 1.7.2. --- Continuous Positive Airway Pressure (CPAP) --- p.14 / Chapter 1.7.3. --- Corticosteroids --- p.15 / Chapter 1.7.4. --- Leukotriene Receptor Antagonist --- p.16 / Chapter 1.8. --- Complications of Childhood OSAS / Chapter 1.8.1. --- Growth Failure --- p.17 / Chapter 1.8.2. --- Neurocognitive Abnormalities --- p.19 / Chapter 1.8.3. --- Cardiovascular Abnormalities --- p.20 / Chapter CHAPTER 2 --- Cardiovascular Complications of OSAS in Adults (Literature Review) / Chapter 2.1. --- Acute Effects of OSAS on Cardiovascular System --- p.21 / Chapter 2.2. --- Chronic Effects of OSAS on Cardiovascular System --- p.23 / Chapter 2.3. --- Hypertension --- p.24 / Chapter 2.4. --- Heart Failure --- p.28 / Chapter 2.5. --- Pulmonary Hypertension --- p.30 / Chapter 2.6. --- Arrhythmias --- p.31 / Chapter 2.7. --- Cardiac Ischemia and Vascular Disease --- p.33 / Chapter 2.8. --- Stroke --- p.34 / Chapter CHAPTER 3 --- Cardiovascular Complications of Childhood OSAS (Literature Review) / Chapter 3.1. --- Blood Pressure --- p.37 / Chapter 3.2. --- Ventricular Structure and Function --- p.40 / Chapter 3.3. --- Arterial Distensibility --- p.42 / Chapter 3.4. --- Heart Rate Variability --- p.42 / Chapter CHAPTER 4 --- Ambulatory Blood Pressure in Children with OSAS / Chapter 4.1. --- Introduction --- p.44 / Chapter 4.2. --- Methods / Chapter 4.2.1. --- Subjects and Study Design --- p.46 / Chapter 4.2.2. --- Polysomnography (PSG) --- p.47 / Chapter 4.2.3. --- Ambulatory Blood Pressure Measurement (ABPM) --- p.49 / Chapter 4.2.4. --- Statistical Analysis --- p.50 / Chapter 4.3. --- Results / Chapter 4.3.1. --- Subject Characteristics --- p.52 / Chapter 4.3.2. --- Blood Pressure during Wakefulness --- p.55 / Chapter 4.3.3. --- Blood Pressure during Sleep --- p.57 / Chapter 4.4. --- Discussion --- p.62 / Chapter 4.5. --- Conclusion --- p.70 / Chapter CHAPTER 5 --- Cardiac Remodeling and Dysfunction in Children with OSAS / Chapter 5.1. --- Introduction --- p.71 / Chapter 5.2. --- Methods / Chapter 5.2.1. --- Subjects and Study Design --- p.72 / Chapter 5.2.2. --- Polysomnography (PSG) --- p.74 / Chapter 5.2.3. --- Conventional Echocardiography --- p.75 / Chapter 5.2.4. --- Tissue Doppler Imaging --- p.76 / Chapter 5.2.5. --- Statistical Analysis --- p.77 / Chapter 5.3. --- Results / Chapter 5.3.1. --- Study Population --- p.79 / Chapter 5.3.2. --- Polysomnographic Findings --- p.79 / Chapter 5.3.3. --- Echocardiographic Findings / Chapter 5.3.3.1. --- Right Ventricle --- p.81 / Chapter 5.3.3.2. --- Left Ventricle --- p.83 / Chapter 5.3.4. --- Treatment Effect --- p.86 / Chapter 5.4. --- Discussion --- p.90 / Chapter 5.5. --- Conclusion --- p.95 / Chapter CHAPTER 6 --- Conclusion --- p.96 / APPENDIX I Hong Kong Children Sleep Questionnaire (Chinese) --- p.xvii / APPENDIX II Hong Kong Children Sleep Questionnaire (English) --- p.xxii / REFERENCES --- p.xxvii

No description available.

<p>Repolarization inhomogeneity is arrhythmogenic. QT dispersion (QTd) is an easily accessible ECG-variable, related to the repolarization and shown to carry prognostic information. It was originally thought to reflect repolarization inhomogeneity. Lately, arguments have been risen against this hypothesis. Other measures of inhomogeneity are being investigated, such as nondipolar components from principal component analysis (PCA) of the T-wave. In all here described populations, continuous 12-lead ECG was collected during the initial hours of observation and secondary parameters used for description of a large number of ECG-recordings.</p><p>Paper I studied QTd in 548 patients with chest pain with a median number of 985 ECG-recordings per patient. Paper II explored a spatial aspect of QTd in 276 patients with unstable coronary artery disease. QTd and a derived localized ECG-parameter were compared to angiographical measures. QTd, expressed as the mean value during the observation was a powerful marker of risk. It was however not effective in identifying high-risk patients. Variations in QTd contained no additional prognostic information. In unstable coronary artery disease, QTd was increased by a mechanism unrelated to localization of the disease.</p><p>Two relevant conditions for observing repolarization inhomogeneity might occur with conduction disturbances and during initial course of ST-elevation myocardial infarction (STEMI). Paper III compared the PCA-parameters of the T-wave in 135 patients with chest pain and conduction disturbance to 665 patients with normal conduction. Nondipolar components were quantified by medians of the nondipolar residue (TWRabsMedian) and ratio of this residue to the total power of the T-wave (TWRrelMedian). Paper IV described the changes in the nondipolar components of the T-wave in 211 patients with thrombolyzed STEMI. TWRabsMedian increased with increasing conduction disturbance and contained a moderate amount of prognostic information. In thrombolyzed STEMI, TWRabsMedian was elevated and has an increased variability. A greater decrease in absolute TWR during initial observation was seen in patients with early ST-resolution. Nondipolar components do however not reflect identical ECG-properties as the ST-elevation and their change does not occur at the same time.</p>

Repolarization inhomogeneity is arrhythmogenic. QT dispersion (QTd) is an easily accessible ECG-variable, related to the repolarization and shown to carry prognostic information. It was originally thought to reflect repolarization inhomogeneity. Lately, arguments have been risen against this hypothesis. Other measures of inhomogeneity are being investigated, such as nondipolar components from principal component analysis (PCA) of the T-wave. In all here described populations, continuous 12-lead ECG was collected during the initial hours of observation and secondary parameters used for description of a large number of ECG-recordings. Paper I studied QTd in 548 patients with chest pain with a median number of 985 ECG-recordings per patient. Paper II explored a spatial aspect of QTd in 276 patients with unstable coronary artery disease. QTd and a derived localized ECG-parameter were compared to angiographical measures. QTd, expressed as the mean value during the observation was a powerful marker of risk. It was however not effective in identifying high-risk patients. Variations in QTd contained no additional prognostic information. In unstable coronary artery disease, QTd was increased by a mechanism unrelated to localization of the disease. Two relevant conditions for observing repolarization inhomogeneity might occur with conduction disturbances and during initial course of ST-elevation myocardial infarction (STEMI). Paper III compared the PCA-parameters of the T-wave in 135 patients with chest pain and conduction disturbance to 665 patients with normal conduction. Nondipolar components were quantified by medians of the nondipolar residue (TWRabsMedian) and ratio of this residue to the total power of the T-wave (TWRrelMedian). Paper IV described the changes in the nondipolar components of the T-wave in 211 patients with thrombolyzed STEMI. TWRabsMedian increased with increasing conduction disturbance and contained a moderate amount of prognostic information. In thrombolyzed STEMI, TWRabsMedian was elevated and has an increased variability. A greater decrease in absolute TWR during initial observation was seen in patients with early ST-resolution. Nondipolar components do however not reflect identical ECG-properties as the ST-elevation and their change does not occur at the same time.

Background: The twisting motion of the left ventricle (LV), with clockwise rotation at the base and counter clockwise rotation at the apex during systole, is a vital part of LV function. Even though LV rotation has been studied for decades, the rotation pattern has not been described in detail. By the introduction of speckle tracking echocardiography measuring rotation has become easy of access. However, the axis around which the LV rotates has never before been assessed. The aims of this thesis were to describe the rotation pattern of the LV in detail (study I), to assess RV apical rotation (study II), develop a method to assess the rotation axis (study III) and finally to study the effect of regional ischemia to the rotation pattern of the LV (study IV). Methods: Healthy humans were examined in study I-III and the final study populations were 40 (60±14 years), 14 (62±11 years) and 39 (57±16 years) subjects, respectively. In study IV six young pigs (32-40kg) were studied. Standard echocardiographic examinations were performed. In study IV the images were recorded before and 4 minutes after occlusion of left anterior descending coronary artery (LAD). Rotation was measured in short axis images by using a speckle tracking software. By development of custom software, the rotation axis of the LV was calculated at different levels in every image frame throughout the cardiac cycle. Results: Study I showed significant difference in rotation between basal and apical rotations, as well as significant differences between segments at basal and mid ventricular levels. The rotation pattern of the LV was associated with different phases of the cardiac cycle. Study II found significant difference in rotation between the LV and the RV. RV rotation was heterogeneous and bi-directional, creating a ´tightening belt action´ to reduce it circumference. Study III indicated that the new method could assess the rotation axis of the LV. The motion of the rotation axes in healthy humans displayed a physiological and consistent pattern. Study IV found a significant difference in the rotation pattern, between baseline and after LAD occlusion, by measuring the rotation axes, but not by conventional measurements of rotation. AV-plane displacement and wall motion score (WMS) were also significantly changed after inducing regional ischemia. Conclusion: There are normally large regional differences in LV rotation, which can be associated anatomy, activation pattern and cardiac phases, indicating its importance to LV function. In difference to the LV, the RV did not show any functional rotation. However, its heterogeneous circumferential motion could still be of importance to RV function and may in part be the result of ventricular interaction. The rotation axis of the LV can now be assessed by development of a new method, which gives a unique view of the rotation pattern. The quality measurements and results in healthy humans indicate that it has a potential clinical implication in identifying pathological rotation. This was supported by the experimental study showing that the rotation axis was more sensitive than traditional measurements of rotation and as sensitive as AV-plane displacement and WMS in detecting regional myocardial dysfunction.

Despite the currently recommended dual antiplatelet treatment (DAT) with aspirin and P2Y12 inhibition in patients with coronary artery disease (CAD) there is a risk of adverse clinical outcome. Pharmacodynamic (PD) poor response to clopidogrel occurs in ~ 30% of clopidogrel-treated patients and is associated with an increased risk of recurrent thrombotic events. The aims of this thesis were to compare the PD and pharmacokinetic effects of clopidogrel 600 mg loading dose (LD)/ 75 mg standard maintenance dose (MD) with the novel P2Y12 inhibitor prasugrel 60 mg LD/10 mg MD, in 110 patients with CAD. The mechanisms behind clopidogrel poor response were investigated by assessing the pharmacodynamics after adding clopidogrel active metabolite (AM) and genotyping for variation in CYP-genes involved in thienopyridine metabolism. In another study, we compared the on-clopidogrel platelet reactivity of patients with stent thrombosis (ST) (n=48) or myocardial infarction (MI) (n=30) while on DAT and their matched controls (n=50 + 28). Prasugrel achieved a faster and greater P2Y12-mediated platelet inhibition than clopidogrel measured with light transmission aggregometry, VASP and VerifyNow® P2Y12. Prasugrel’s greater platelet inhibition was associated with higher exposure of AM. The addition of clopidogrel AM led to maximal platelet inhibition in all subjects, suggesting that prasugrel’s greater antiplatelet effect was related to more efficient AM generation compared to that of clopidogrel. Lower levels of AM as well as less platelet inhibition were seen in clopidogrel-treated patients with reduced-metabolizer genotype CYP2C19 compared to those with normal genotype. Patients with ST while on DAT showed higher on-clopidogrel platelet reactivity compared to matched stented controls. Patients with spontaneous MI after stenting did not. In conclusion, these results showed a high rate PD poor response to a high bolus dose of clopidogrel because of a partly genetically caused lower generation of AM which could be overcome by prasugrel treatment. In patients after coronary stenting, clopidogrel poor response was related to ST but not to spontaneous MI, illustrating difficulties in optimizing treatment with clopidogrel based on platelet function or genetic testing in individual patients.

Le ventricule droit (VD) fut longtemps oublié par les cardiologues mais l'expérience a montré qu'il conditionne le pronostic des patients dans de nombreuses situations cliniques et que l'évaluation de sa fonction est un élément diagnostique majeur lorsqu'une pathologie du VD est suspectée. Après une revue des différentes méthodes d'évaluation de la fonction ventriculaire droite, cette thèse explore tout d'abord les limites des deux méthodes d'évaluation du VD les plus répandues (IRM et échographie) : Premièrement, les indices de contraction longitudinale en échographie ne permettent pas de dépister correctement les altérations de la fraction d'éjection dans la situation d'une surcharge volumétrique notamment. Deuxièmement, l'IRM en coupes petit-axe présente des difficultés importantes de délinéation de l'endocarde. Les principaux écarts de contours entre deux observateurs concernent l'infundibulum pour 40% et la valve tricuspide pour 40% également. Dans une troisième partie, nous proposons un indice géométrique simple à calculer lors d'un examen IRM et permettant de pré-sélectionner les patients nécessitant une étude précise du VD. Cet indice validé sur 340 patients réduit le temps opérateur de 35% sans entrainer d'erreur diagnostique. La dernière partie de cette thèse s'intéresse 'a la mesure de la vitesse tissulaire du myocarde et aux indices fonctionnels qui en dérivent. Cette mesure nécessite une haute résolution temporelle qui peut être atteinte en IRM en respiration libre au prix d'une augmentation de la durée d'acquisition.

The purpose of this investigation was to examine whether a single 10 minute bout of exercise, performed at multiple intervals throughout the day to equal 30 minutes, can effectively elicit post-exercise hypotension (PEH). Secondly, it is important to explore whether a light (40% VO2R) or moderate (70% VO2R) intensity is required to elicit PEH within 10 minutes. Subjects (N=11) completed a VO2max test utilizing the Bruce Treadmill protocol. Each subject returned within 3 – 5 days to complete two separate exercising trials. A counter balanced system was employed so that each subject did not perform the same intensity rotation (Counter Balance 1 = 40% VO2R and 70% VO2R for session 1 and session 2, respectively; Counter Balance 2 = 70% VO2R and 40% VO2R for session 1 and session 2). The first session consisted of 3 sessions (morning, noon, evening) separated by an average of 3.5 hours at one of two intensities (40% VO2R or 70% VO2R). The second group of sessions were performed identical to the first, however, the intensity was altered depending upon counter balance. Baseline BP was measured prior to exercising. After each session, BP was measured at 2 intervals for the morning and noon sessions (immediately following and 20 minutes post-exercise); and at 3 intervals for the evening sessions (60 minutes post-exercise added) for both intensities. At 40% VO2R, BP decreased significantly at the morning (p = 0.007), noon (p = 0.018) and evening (p = 0.010) sessions at the 20 minute post-exercise interval. Although not significantly different, BP was observed to be lower at 60 minutes post-exercise interval. During the 70% VO2R session, BP was significantly lower at the morning 20 minute (p = .029) and evening 60 minute post-exercise measurements (p = .006) when compared to baseline. There was no significant difference noted between 40% and 70% VO2R intensities at eliciting a drop in BP at any interval at any time point. Although not statistically significant, 70% VO2R appeared to produce a further decrease at the 60 minute post-exercise measurement (102 mmHg) than did the 40% session (106 mmHg). The results of this study indicate that PEH may be elicited after a single 10 minute exercise session. Furthermore, multiple bouts of 10 minutes produce an accumulated decrease in BP that can be observed at the completion of the day.

The overall aim of this thesis was to describe patients’ and spouses’ experiences of suspected acute myocardial infarction in the pre-hospital phase. A descriptive survey study was conducted to identify various factors influencing patient delay in 381 patients with suspected myocardial infarction hospitalised at a Coronary Care Unit (I) and ambulance utilisation among 110 myocardial infarction patients (II). In order to obtain a deeper understanding of the myocardial infarction patients’ own conceptions about the event, an interview study with a phenomenographic approach was conducted with 15 strategically selected myocardial infarction patients (III), within 72 hours after admission to hospital. Finally, the pre-hospital experiences of 15 spouses of myocardial infarction patients were also studied through interviews with a phenomenographic approach, within 48 hours after the affected partner’s admittance to hospital (IV). The results showed that 59% of the patients with suspected acute myocardial infarction delayed &gt; 1 hour after onset of symptoms. The most common reasons given for delay in seeking hospital admittance were: (1) Did not consider the symptoms as to be severe enough that they warranted hospital care, (2) thought the symptoms to be temporary and that they would disappear, (3) the chest pain was more of a dull pain, (4) or, as one third of the patients chose to do, contacted the general practitioner instead of going directly to the hospital (I). Furthermore, as a first action, 59% consulted their spouse for advice about what to do henceforth. The most common reason for additional delay when the decision to go to hospital had already been taken was that the myocardial infarction patients stated that they were unaware of the advantages of a rapid decision-making process. Sixty percent went by ambulance, but it was the spouse (40%) or the personnel at the general practitioner’s office (32%) who called the emergency service number, rather than the patient him/her self (5%). The most frequently given reasons for not choosing ambulance, were that the patients did not perceive their symptoms as being serious enough to require ambulance transportation (43%), followed by that they had not thought about ambulance as an alternative at all (38%). As a third reason for not going by ambulance, the patients stated that it was unnecessary to call an ambulance when being affected by symptoms related to a myocardial infarction (26%). The patients who called an ambulance differed in some respects from those who went by private alternatives; patients with large infarctions (ST-Elevation Myocardial Infarction) went by ambulance more frequently, as did patients suffering from nausea and severe chest pain (II). The patients expressed in the interviews how the interaction with others, described as the need for supportive environment, worries for the family and the utilisation of the health-care resources, was of great importance in the pre-hospital phase. Likewise, symptom awareness, with earlier experiences of a similar situation to compare with, denying the seriousness of the situation and the use of different self-care strategies, were important in order to manage the situation. Vulnerability, expressed as anxiety and a lack of control, also influenced the decision-making process in the pre-hospital phase (III). Spouses seemed to have a strong influence on the course of events when their partner suffered an acute myocardial infarction and it emerged from the interviews how the spouses in many cases were influenced into sharing the denial of the affected partner by respecting his/her independence. The spouses accepted the partner’s need for control; took earlier marital roles and experiences into account; restraining own emotions and seeking agreement with their partners, contributing to delay. However, being resourceful by sharing the experience; having knowledge; understanding the severity; being rational and consulting others when needed, seemed to have a positive influence on the decision time in the pre-hospital phase (IV). Conclusion: The reasons for delaying or not in the pre-hospital phase, as well as the reasons for utilising the ambulance services or not, varied considerably between individuals. Earlier experiences of MI did not influence what actions to take; instead patients’ feelings, emotional attitudes to MI symptoms, inadequate coping strategies, and spouses’ influences were important components in the pre-hospital phase.