Magnetic Resonance Imaging of the Neonatal Cardiovascular System : Impact of Patent Ductus Arteriosus

The incidence of premature birth is increasing in absolute number and as a proportion of all births around the world. Many pathologies seen in this cohort are related to abnormal blood supply. Fetal and premature cardiovascular systems differ greatly as to maintain adequate blood flow to the developing organs in the uterine and extra-uterine environments require very different circulations. Subsequently following preterm birth the immature cardiovascular system undergoes abrupt adaptations, often resulting in the prolonged patency of the fetal shunt, ductus arteriosus. The impact of a patent ductus arteriosus (PDA) is poorly understood. However it is thought that large ductal shunt volumes may result in congestive cardiac failure and systemic hypo-­‐perfusion. Cardiac MRI has contributed greatly to the understanding of many cardiovascular diseases and congenital defects in paediatric and adult patients. Translating these imaging techniques to assess the preterm cardiovascular system requires careful optimization due to their condition, size and significantly increased heart rate. The work presented in this thesis employs multiple functional CMR techniques to investigate the preterm cardiovascular system in the presence and absence of PDA and the resultant cardiac function. A novel technique utilizing PC MRI to quantify PDA shunt volume and its impact on flow distribution is presented. Despite large shunt volumes, systemic circulation remained within normal range, although slight reduction is detectable when assessed at group level. Subsequently the impact of PDA and associated increased work load on left ventricular dimensions and function was then investigated using SSFP imaging. Results indicated that cardiac function was maintained even in the presence of large shunt volumes. Finally 4D PC sequences were employed to evaluate pulse wave velocity and flow regime within the preterm aorta, demonstrating the feasibility of hemodynamic assessment in this cohort. The findings of these studies provide insight into the impact of PDA. The reliable measurement and assessment of preterm cardiovascular system provides the potential to improve the understanding of the development and effects of certain pathologies seen in this cohort.Open Acces

Computational estimation of haemodynamics and tissue stresses in abdominal aortic aneurysms

'o e Abdominal aortic aneurysm is a vascular disease involving a focal dilation of the aorta. The exact cause is unknown but possibilities include infection and weakening of the connective tissue. Risk factors include a history of atherosclerosis, current smoking and a close relative with the disease. Although abdominal aortic aneurysm can affect anyone, it is most often seen in older men, and may be present in up to 5.9 % of the population aged 80 years. Biomechanical factors such as tissue stresses and shear stresses have been shown to play a part in aneurysm progression, although the specific mechanisms are still to be determined. The growth rate of the abdominal aortic aneurysm has been found to correlate with the peak stress in the aneurysm wall and the blood flow is thought to influence disease development. In order to resolve the connections between biology and biomechanics, accurate estimations of the forces involved are required. The first part of this thesis assesses the use of computational fluid dynamics for modelling haemodynamics in abdominal aortic aneurysms. Boundary conditions from the literature o

Implantable cardioverter defibrillator treatment in patients with hypertrophic cardiomyopathy

Background: Hypertrophic cardiomyopathy (HCM) is a heterogeneous disease with various clinical manifestations, including sudden cardiac death, which can be prevented by an implantable cardioverter defibrillator (ICD). Aims: The general aim of this thesis was to elucidate different aspects of ICD treatment in patients with HCM. This includes the use of ICDs among HCM patients with focus on risk stratification for ventricular arrhythmias, mortality, and cause of death; assessment of health-related quality of life; qualitative aspects of living with an ICD; and characterization using positron emission tomography (PET) to explore risk markers for sudden death. Methods: The Swedish Pacemaker and ICD Registry was retrieved to identify eligible patients. Data from the National Patient Registers, the Cause of Death Register, Statistics Sweden, and medical records were used. Health-related quality of life was assessed using SF-36. Interviews were analyzed by hermeneutics and latent content analysis. PET and echocardiography were performed. Results and Conclusions: In Paper Ⅰ, the nationwide cohort of unselected HCM patients with ICDs was based on established risk factors for sudden cardiac death at the time. ICDs effectively terminated potentially life-threatening ventricular arrhythmias in HCM. The cumulative incidences of first appropriate ICD therapy at 1 year, 3 years, and 5 years were 8%, 15%, and 21%, respectively. Left ventricular ejection fraction less than 50% and atrial fibrillation were strong predictors of appropriate ICD therapy. In Paper Ⅱ, among HCM patients with ICDs, the main cause of death is deterioration of systolic function leading to end-stage heart failure. The risk of sudden cardiac death was almost eliminated. Still, there was an increased risk of death (standardized mortality ratio 3.4) compared to the Swedish general population matched for age, sex, and calendaric time. In Paper Ⅲ, generic health-related quality of life, both mental and physical components, was lower in HCM patients with ICDs than in Swedish age- and sex-matched population norms. Systolic heart failure and atrial fibrillation are determinants of low health-related quality of life, especially physical functioning. In Paper Ⅳ, based on qualitative interpretation, HCM patients with ICDs perceive poor health due to limiting dyspnea but accept the change in lifestyle. They feel grateful for their device, which gives them hope during the life course despite necessary restrictions and adaptation, even after experiencing inappropriate shocks. The knowledge about the disease and device therapy varies substantially and the support from the health care providers is generally constrained to technical issues rather than an attempt at a holistic approach. In Paper Ⅴ, HCM patients with ICDs represent advanced disease manifestation determined as decreased myocardial blood flow at stress, altered oxidative metabolism, and sympathetic denervation using the tracers 15O-water, 11C-acetate, and 11C-HED during PET exams. The endocardium/epicardium myocardial blood flow gradient at adenosine stress is lower in HCM patients with nonsustained ventricular tachycardia, which provides a potential marker for risk stratification of sudden cardiac death

Quantitative Analysis of Left Ventricular Function by Two-Dimensional Echocardiography

With the introduction of thrombolytic therapy in patients with acute myocardial infarction in the early eighties, both the outcome and prognosis of acute myocardial infarction improved considerably.I.II At the same time, the need for an accurate and noninvasive method to assess left ventricular function was increasing. In that period, technological and computer developments resulted in improved two-dimensional echocardiographic image quality and analytic methods. However, two-dimensional echocardiography was not available in most coronary care units and the use of Doppler echocardiography was just emerging. The first color Doppler flow imaging systems, which allow the visualization of the intracardiac blood flow, did not arrive before the mideighties. All of these newer technologies with their improved and additional diagnostic capabilities were a major stimulus to study patients with an acute myocardial infarction in the coronary care unit. To this end we designed a study to investigate the following questions: I. early diagnosis and severity of an acute myocardial infarction 2. early diagnosis of the complications of an acute myocardial infarction 3. prognosis of an acute myocardial infarction and its complications 4. evaluation of therapeutical interventions in patients with an acute myocardial infarction

Modulography: elasticity imaging of atherosclerotic plaques

Modulography is an experimental elasticity imaging method. It has potential to become an all-in-one in vivo tool (a) for detecting vulnerable atherosclerotic coronary plaques, (b) for assessing information related to their rupture-proneness and (c) for imaging their elastic material composition. Modulography determines a cross-sectional image of the elasticity distribution (=Young's modulus) from deformation (=strain) that is processed from intravascular ultrasound (IVUS) measurements. By looking at this image, cardiologists and other researchers can directly identify and characterize soft and stiff plaque-components of thin-cap fibroatheromas and of heterogeneous plaques. As a diagnostic and pharm

The relationship between aortic stiffness, health related quality of life and post-operative organs recovery (cardiac, renal and cognitive) following aortic valve replacement

Background: Aortic stiffness as measured by pulse wave velocity (PWV) is a predictor of cardiovascular disease and other outcomes in different diseased and healthy populations, independent of traditional risk factors. The relationships between PWV measurement, global functional outcome and injury to the brain, kidney, and heart have never been examined in cardiac surgery patients. Objective: The objective of this project was to assess the relationship between aortic stiffness and health related quality of life (QoL), cognitive function, acute kidney injury (AKI), and cardiac function in patients undergoing aortic valve replacement (AVR). Methods: Aortic PWV, QoL, cognitive function, left ventricular (LV) function and NYHA class were assessed pre- and post-operatively (409 ± 159 days). The brain injury biomarker, N-methyl-D-aspartate receptor antibody (NR2Ab), was measured pre-operatively only. The biomarker of myocardial strain, B-type natriuretic peptide (BNP), and the novel AKI biomarker, neutrophil gelatinase-associated lipocalin (NGAL), were measured pre-operatively, and at 3 h and 18-24 h post-CPB. Results: Fifty-six patients (16 females; mean age, 71 ± 8.4 years) were included in this study, of which 50 (89%) patients attended the follow-up visit. No relationship was found between the degree of aortic stenosis (AS) and PWV, and AVR had no effect on aortic stiffness post-operatively. QoL and NYHA class significantly improved, while cognitive function did not deteriorate after AVR. High PWV is independently related to poorer QoL, cognitive function levels and NYHA class both pre- and post-operatively. PWV was not related to LV function, BNP or NGAL levels, but it was independently related to the level of NR2Ab. PWV did not correlate with AKI which was developed in 30% of the cases. Early post-operative plasma level of NGAL is the earliest predictive marker of post-operative AKI and the need for early medical renal intervention. Pre-operative BNP level was significantly and negatively correlated with pre-operative LV function, AS (valve area), and NYHA class in the post-operative follow-up period. Conclusion: In AVR patients, PWV is independently related to global functional status, cognitive function and brain injury biomarkers, but is not related to AKI or myocardial strain.Open Acces