The assessment of the coronary microcirculation using the index of microvascular resistance in patients with ischaemic heart disease

© 2013 Dr. Jamie J. W. LaylandDespite improvements in medical therapy, ischaemic heart disease (IHD) remains a significant cause of morbidity and mortality in western societies. The link between epicardial stenosis and myocardial ischaemia is well documented, yet improvements in outcome have come from a focus on myocardial perfusion rather than just restoration of epicardial flow. Myocardial perfusion is comprised of collateral flow; epicardial flow and microcirculatory flow yet the key regulator of this process is the coronary microcirculation. Thus focusing on the coronary microcirculation may provide a further pathway for improving outcomes in patients with ischaemic heart disease. However, factors affecting the coronary microcirculation, in particular the effect of percutaneous coronary intervention, have not extensively studied. Furthermore, the role of the coronary microcirculation in defining key relationships in coronary physiology is also unresolved. There are a variety of methods that can be utilized to assess the coronary microcirculation both invasive and non-invasive. Each method has its own potential advantages and disadvantages but invasive methods would seem intuitively more useful amongst patients presenting to the catheter laboratory. The Index of Microvascular Resistance (IMR) is a novel invasive technique that has been extensively validated in both in-vivo and in-vitro models. The principle aim of this thesis is to use the index of microvascular resistance to examine the coronary microcirculation in patients with ischaemic heart disease. Specifically I will examine the predictors of IMR and the influence of the collateral circulation on IMR in patients with stable angina. I will also examine the predictors of microcirculatory dysfunction following PCI and look at factors both clinical and biochemical, effecting IMR measured following PCI. I will also use IMR to define controversial relationships in coronary physiology. Specifically I will examine the relationship between coronary flow reserve and fractional flow reserve and also the ability of the microcirculation to vasodilate in patients with NSTEMI. A variety of patients with IHD were recruited into the study. 80 patients with stable angina, 50 patients with NSTEMI and 40 patients with STEMI were included in the analysis. Coronary Physiological measurements were taken pre and following PCI in the culprit vessel and where possible, in an angiographically normal reference vessel. Bloods were taken at the time of the procedure and sequentially every 6 to 12 hours up to 24 hours following percutaneous coronary stenting. In summary, the main findings of this thesis are: i) Epicardial Stenosis does not increase microvascular resistance when collateral flow is accounted for. ii) The resting status of the coronary microcirculation is a key predictor of post PCI coronary microvascular function. iii) The resting status of the coronary microcirculation is an independent predictor of periprocedural myocardial infarction. Specifically localized impairment of the coronary microcirculation as determined by the relative pre IMR ratio was a predictor of periprocedural myocardial infarction. iv) The ability of the coronary microcirculation to vasodilate is preserved in selected patients with NSTEMI. This property is directly correlated with the baseline level of IMR and myocardial injury and suggests that the use of diagnostic tests that rely on hyperemia may be suitable for use in selected patients with NSTEMI. v) The discordance between fractional and coronary flow reserve is not explained by variations in microvascular resistance. The findings of this PhD are novel and have implications for the prediction of myocardial injury caused by percutaneous coronary intervention (PCI). Specifically that targeting a high IMR prior to stenting may allow for further improvements in outcome in elective PCI. I have also clearly shown (in the largest studied cohort to date) that the measurement of collateral flow is mandated when calculating microvascular resistance to avoid overestimation. Furthermore, that maximal hyperemia is possible in high acuity patients with non-ST segment myocardial infarction, potentially allowing the use of diagnostic tests such as fractional flow reserve that rely on an intact microcirculation. This may have far reaching clinical implications but warrants confirmation in a large prospective, randomised study