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Title: The structural determinants and functional consequences of left ventricular outflow tract obstruction in hypertrophic cardiomyopathy
Author: Critoph, C. H.
ISNI:       0000 0004 5352 2558
Awarding Body: University College London (University of London)
Current Institution: University College London (University of London)
Date of Award: 2014
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Hypertrophic cardiomyopathy (HCM) is the commonest inherited cardiac condition. Many patients have resting or provocable left ventricular outflow tract (LVOT) obstruction. Symptoms treated with drugs or surgery may improve. There is a need to improve the clinical assessment in individual patients, because of the often poor correlation between symptoms and LVOT gradient, and the association with complications such as stroke, heart failure and sudden cardiac death. In addition, in a proportion of patients with significant LVOT gradients, relief of obstruction does not adequately improve symptoms. Reduced angulation between the inter-ventricular septum and the aorta is a determinant of LVOT obstruction. However, lack of a standardised method of measurement in HCM without recourse to complex 3-D imaging limits the usefulness of this parameter in routine practice. Transthoracic echocardiography is widely available, and can be used to measure aorto-septal angulation. However, data in HCM are lacking. I validated a simple measurement of aorto-septal angulation using 2-D echocardiography and cardiac magnetic resonance imaging and determined its relation to provocable LVOT obstruction in HCM. I showed this technique to be easy, reproducible, comparable to magnetic resonance imaging, and can be quickly calculated using standard echocardiographic software. Patients have a smaller aorto-septal angle than controls, where it is associated with higher peak LVOT gradient. A reduced aorto-septal angle is highly specific for provocable LVOT obstruction and should prompt further evaluation in symptomatic patients without resting gradients. I used a non-invasive technique for measuring cardiac output to determine the relation between LVOT obstruction, cardiac output and peripheral oxygen utilisation in patients with HCM during exercise. I demonstrated that cardiac output response to exercise is impaired, caused largely by failure to appropriately augment stroke volume. LVOT obstruction is associated with greater impairment of stroke volume at peak exercise and is an independent and modifiable predictor of cardiac output reserve. However, heterogenous responses are seen between patients who otherwise appear similar using standard clinical criteria. There is therefore a strong argument for the individualisation of therapy in patients with LVOT obstruction. Invasive therapies to reduce gradients may work better in those with genuine obstruction to the outflow of blood, rather than for example myocardial ischaemia or mitral regurgitation. The non-invasive measurement of haemodynamic indices during exercise is practical, aids understanding of the complex physiological basis behind symptoms and may help to tailor therapy for HCM, and in particular LVOT obstruction.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available