Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.650694
Title: Chronic thromboembolic pulmonary vascular disease : physiological concepts and genetic predisposition
Author: McCabe, Colm
ISNI:       0000 0004 5357 0496
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2014
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Abstract:
Chronic thromboembolic pulmonary hypertension (CTEPH) is an uncommon sequela of acute pulmonary embolism and, untreated, leads to right ventricular (RV) failure and death. Despite its growing recognition, methods for the detection of early RV insufficiency and prediction of clinical deterioration, important to optimum preservation of RV function, are currently suboptimal. Furthermore, underlying genetic predisposition to CTEPH, unexplained by defective fibrinolysis, remains largely unexplored. The RV's physiological response to chronic thromboembolic obstruction is arguably best described by RV pressure volume loops which, historically, are best obtained using the conductance catheter. Although invasive, conductance has an indisputable advantage over current imaging modalities; catheters measure dynamic ventricular pressure and volume throughout the cardiac cycle. Using this technique, abnormal RV pressure volume loops are demonstrated in response to chronic thrombotic obstruction, independent of resting haemodynamic criteria diagnostic of CTEPH. Pressure volume differences and accrual of an exercise gas exchange deficit further suggest early 'subclinical' RV adaptation. The genetic architecture of CTEPH is also explored using high-throughput sequencing of unrelated patients. This shows that rare DNA variants in CTEPH that are predicted to harbour deleterious effects are not over-represented in fibrinolytic pathways. Finally, prognostication in CTEPH is evaluated using a clinical deterioration model which is shown to be predicted by patient-reported outcomes at diagnosis. In conclusion, RV and pulmonary circulatory function in chronic thromboembolic pulmonary vascular disease are inadequately characterised by existing routine methods. Links between the observed physiological deficits, risk of clinical deterioration and abnormal genetic architecture warrant further evaluation in this rare disease.
Supervisor: Wilkins, Martin Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.650694  DOI: Not available
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