Non-invasive evaluation, therapy and transplantation in children with pulmonary arterial hypertension.
Doctoral thesis, UCL (University College London).
Pulmonary hypertension (PHT) is a progressive and ultimately fatal disease. The condition is poorly understood in children. This thesis evaluated non-invasive assessment techniques, experience with epoprostenol, atrial septostomy and lung transplantation in children. As therapy is guided by patients’ functional capacity, studies focused on 6-minute walk test distance (6MWTd) and cardiopulmonary exercise testing (CPET). Age-related normal values of 6MWTd were determined, and the relationship between 6MWTd and CPET was assessed. Echocardiographic markers of impaired myocardial function were investigated using tissue Doppler (TDI) and potential risk-factors of mortality were sought using heart rate variability (HRV) and B-natriuretic peptide (BNP). Parameters of CPET correlated with 6MWTd in highly compromised children but in less impaired children the 6MWT represented a sub-maximal test, indicating that a CPET is required when 6MWTd exceeds 300m. BNP and HRV were related to prognosis but sensitivity and specificity are limited. TDI demonstrated that biventricular function is impaired in children with PHT and that left ventricular impairment cannot be evaluated adequately using conventional echocardiographic techniques. Reviewing our experience with intravenous epoprostenol, it improved functional capacity, survival and could be used safely in children with acceptable morbidity. Atrial septostomy abolished syncope and improved right ventricular function, at the expense of mild systemic arterial oxygen desaturation. Septostomies, with and without a fenestrated device, can close spontaneously with time, stressing the need for a more reliable device. When medical therapies were exhausted, transplantation dramatically improved quality of life and survival. Listing criteria were shown to have been appropriate but more objective criteria are needed. These studies evaluating assessment techniques, prognosticators, and therapies have given further insight into the management of children with PHT. Future work should include assessment of non-invasive magnetic resonance imaging, exploring a combined prognosticator, combination therapy and improving classification of clinical status to optimise therapy and facilitate trials of new, urgently needed medicines.
|Title:||Non-invasive evaluation, therapy and transplantation in children with pulmonary arterial hypertension|
|Open access status:||An open access version is available from UCL Discovery|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Child Health|
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