Paediatrics (RCH) - Theses
Permanent URI for this collection
Search Results
1 - 2 of 2
-
ItemNon-invasive arterial wave analysis in congenital heart disease( 2018)Elevated large arterial stiffness is an independent risk factor for adult cardiovascular and cerebrovascular disease. Arterial dysfunction may already be evident in childhood, and children born preterm, or with a history of congenital cardiac surgery, particularly coarctation of the aorta, have a high burden of adult cardiovascular disease and hypertension. Novel arterial wave analyses such as Wave Intensity (WI) and Wave Power (WP) assess the interaction between the heart and great vessels, providing insights into mechanisms of hypertension. Non-invasive WI/WP analyses rely on accurate acquisition of velocity (U), and diameter (D) with ultrasound. Although ultrasound methods are well suited to measuring peak U, WI/WP rely on mean U, which is difficult to obtain routinely. Local pulse-wave speed (c), a measure of arterial stiffness, can also be determined by constructing PU or ln(D)U loops, which also rely on mean U. Errors in c with PU and ln(D)U loop methods due to inaccurate U were determined using MRI-based verification and simulated virtual cohort. A novel method for acquiring local c, which accounts for errors in U and those related to proximal wave reflections, was developed. This technique allowed for scaling factors to be derived to convert peak U into mean U, enabling WI/WP analysis using widely available clinical equipment. In an animal model, invasive and non-invasive WI/WP analyses were compared. The correlations for WI and WP indices were good, but agreement was poor- with a majority of the bias accounted for by either inaccurate invasive U or non-invasive flow estimation, and to non-invasive underestimation of peak P rates of change. Agreement and correlation for wave-related pressure changes were acceptable, and non-invasive WI analysis detected similar relative changes in wave indices during haemodynamic perturbations. Ex-preterm adolescents born at <28 weeks gestation and largely at appropriate weight for gestational age were found to have elevated systolic blood pressure, with no difference in conventional vascular indices. They had a smaller ascending aorta and greater wave reflection on non-invasive WI assessed in the aorta, which was associated with systolic blood pressure on multivariable analysis. Non-invasive WI/WP was also applied in a study of young adults after coarctation repair. They had higher aortic stiffness, but despite higher carotid IMT, there was no increased carotid stiffness. They had higher aortic WI indices, but not WP. In contrast, in the carotid artery both WI and WP indices were greater. Aortic stiffness was related to forward carotid WP in the coarctation group, but not controls. These findings demonstrate that greater stiffness of the aorta leads to increased transmission of wave energy towards the brain. Non-invasive WI/WP analyses have the potential to be more widely deployed using the methods developed in this thesis, and may yield novel insights into the circulatory phenomena that are encountered in children and young people with congenital cardiac and vascular disease.
-
ItemMinimising complications after surgical repair of coarctation of the aorta( 2018)Coarctation of the aorta is one of the most common congenital heart defects, often requiring surgery soon after birth. In Australia alone, approximately 150 babies are born with coarctation each year with an estimated 3,000 people living with a coarctation repair. Coarctation can no longer be considered a benign condition cured by surgery. There has been renewed interest into the late outcomes after coarctation repair as rates of late aortic arch reobstruction and late hypertension have recently been demonstrated to be much higher than initially expected. Alarmingly, studies have demonstrated that this late hypertension is directly linked to mortality at a young age. Unfortunately, late hypertension is often resistant to conventional antihypertensive medication and its exact mechanism is unknown. This thesis aimed to (i) determine the long-term outcomes after surgical repair of coarctation with a particular focus on determining the mechanisms leading to the development of late hypertension, (ii) examine the impact of an associated bicuspid aortic valve on patients with previous coarctation repair, and (iii) examine the complication of vocal cord paresis after aortic arch repair via sternotomy approach. A broad range of potential mechanisms for late hypertension including mechanical, arterial wall, neural, and genetic factors were all explored. In this thesis, I present our current understanding of the population, their outcomes and risk factors for early and late complications, and, finally, present initial data serving as a foundation for a prospective aortic arch anomaly biobank and hypothesis-generated research. Through a collaboration with the Royal Brompton Hospital, London, UK, this thesis has also resulted in the largest and longest cohort study in the world comprising 834 coarctation patients spanning seven decades of follow-up. Through this thesis, I have demonstrated that: (i) there is likely a high prevalence of late hypertension after coarctation repair, (ii) there is significant device-dependence of 24-hour blood pressure monitoring devices, making the identification of the hypertensive patient challenging, (iii) the risk of late mortality is three times higher than a healthy matched population, with the majority of deaths attributable to complications related to hypertension, (iv) there is four times increased risk of aortic valve and ascending aortic interventions in those with an associated bicuspid aortic valve, (v) the use of extensive aortic arch repair techniques may reduce long-term complications, and (vi) there is a high incidence of left vocal cord paresis after aortic arch repair via sternotomy approach. This journey began when I was an undergraduate medical student investigating the outcomes of patients with coarctation repaired at The Royal Children’s Hospital. This thesis has refined our understanding and management of complications after coarctation repair and will ultimately improve the long-term outcomes of many patients with coarctation of the aorta.