Invasive and non-invasive indices of myocardial ischemia

Recent guidelines for the management of stable coronary artery disease (CAD) and myocardial revascularisation emphasise the importance of the presence of ischaemia for guiding revascularisation. Cardiovascular Magnetic Resonance (CMR) perfusion imaging and fractional flow reserve (FFR) are two methods of physiological ischaemia assessment, one invasive and the other non-invasive. In order that the results are interpreted accurately, it is important to be aware of the limitations and advantages of each technique. These techniques measure different parameters so it is not uncommon that the two tests may lead to differing results in one patient. In addition, the extent and not just the presence of ischaemia are increasingly considered to be an important variable that needs to be considered. The aim of this thesis is to assess the similarities and differences in ischaemia assessment between the two tests, in particular in the assessment of ischaemic burden and also on specific clinical scenarios such as microvascular and multivessel disease. Firstly, a close correlation between the extent of ischaemia measured by CMR and the FFR value itself is demonstrated. FFR measurement has previously been used as an indicator of the presence of ischaemia alone and the relationship with ischaemic extent has never been proven. It is an interesting finding, which lends weight to the strategy of targeted revascularisation aiming for the greatest reduction in ischaemic burden. The FFR value itself as an indicator of ischaemic burden is also useful in centres that do not have access to sophisticated imaging techniques such as CMR. Secondly, another simple method of invasive estimation of ischaemic burden is demonstrated via the use of a functional jeopardy score. This is validated against CMR but is limited by a tendency to overestimate the extent of ischaemia. The use of the FFR value itself, as demonstrated in chapter 4, therefore offers better potential as a marker of ischaemic extent. Two examples of areas where there may be discrepant results are in patients with multivessel disease and patients with microvascular disease. A comparative analysis of the diagnostic accuracy of these two tests in multivessel disease demonstrates reasonable concordance but does lead us to question which test is the diagnostic reference standard. In the discrepant cases, it is unclear whether CMR underestimates or FFR overestimates the number of perfusion territories. Finally, a novel method of non invasively differentiating between multivessel disease and microvascular disease is demonstrated, providing a feasible solution to this diagnostic dilemma. Multivessel CAD and microvascular disease can be accurately distinguished using the novel concept of perfusion dephasing analysis, which analyses the spatio-temporal variability in the distribution of myocardial perfusion to the LV myocardium. An improved diagnostic algorithm of CMR is therefore proposed, including the analysis of the variance of time to peak signal intensity, the most accurate index for perfusion dephasing. This has the potential for patient benefit in the reduction of unnecessary invasive angiography procedures.