Abstract
IntroductionInduction of myocardial ischaemia results in a cascade of left ventricular haemodynamic effects, resulting in myocyte necrosis, scar formation and eventual heart failure, for which treatment is limited. Fundamental to enhancing our understanding of cardiovascular pathophysiology and therapeutics is the assessment of ventricular pump properties. The main aim of this work was to gain a greater understanding of the myocardial-coronary and ventricular-arterial interaction in humans in health and diseased states.
Methods
Simultaneous invasive left ventricular (LV) pressure-volume (PV) (by use of a conductance catheter) and intra-coronary haemodynamic assessment (dual-sensor pressure-flow wire) were performed in the catheterisation laboratory. A novel software system was developed to perform simultaneous analysis of PV loop and coronary haemodynamic data. In-vitro and in-vivo studies were performed for calibration; PV loop recordings from patients were used for validation.
Results
1) Using wave intensity analysis, the origin of the coronary wave energies were described, and their temporal relationship with the cardiac cycle was established. In the absence of autoregulation a direct relationship was found to exist between LV elastance and coronary flow velocity.
2) Assessment of coronary haemodynamics and LV PV measurements were performed during supine exercise to provoke ischaemia, with a control group comparator. Ischaemia led to a rightward shift in end-systolic and end-diastolic PV relations; VA interaction was adversely affected during ischaemia compared to control.
3) The effects of nitrates in patients with coronary artery disease were examined. Nitrates induced vasodilatation of the systemic vasculature and coronary circulation, decreasing myocardial oxygen consumption and inducing stenosis dilatation.
4) 3D speckle tracking echocardiography was performed in patients with preserved LV function and coronary artery disease followed by PV loop assessment. Parameters of strain correlated well with contractility indices in-vivo; thus has potential for use in prognostication and risk stratification.
5) The haemodynamic mechanisms of percutaneous ventricular restoration (PVR) therapy are not understood. Patients underwent PVR implantation and LV PV loops were recorded pre- and post-PVR and at 6-month follow up. PVR decreased dyssynchrony, LV volumes and induced reverse remodelling with improved contractility.
Conclusions
Development of software enabled understanding of the cardiac-coronary interaction: coronary wave energies were shown to be dependent on V-A interaction rather than myocardial-coronary interaction. Coronary systolic flow was directly related to LV elastance on abolition of autoregulation. Systemic response to demand ischaemia was described, as were the anti-anginal effects of nitrates; 3D deformation imaging was validated as a prognostic tool for subclinical heart disease and PVR was shown to induce reverse remodelling.
| Date of Award | 2017 |
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| Original language | English |
| Awarding Institution |
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| Supervisor | Simon Redwood (Supervisor) & Michael Marber (Supervisor) |