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Title: Coronary physiology of the stressed heart
Author: Williams, Rupert Philip Charles
ISNI:       0000 0004 5991 0922
Awarding Body: King's College London
Current Institution: King's College London (University of London)
Date of Award: 2016
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Background Highest rates of exertion related cardiac death occur during cold air inhalation (CAI): e.g. shovelling snow, but the pathophysiology is unclear. Coronary micro-vascular resistance (MVR) is the major factor regulating coronary blood flow and subsequent myocardial perfusion. Patients with significant coronary artery disease may be more prone to adverse events due to a reduced vasodilator reserve. Novel intracoronary wires, that simultaneously measure coronary artery pressure (Pd) and coronary blood flow (CBF) allow quantification of MVR, enabling physiological investigation of the effects of CAI during exercise. Study 1. hMR versus IMR at predicting microvascular dysfunction. We compared headto- head, the diagnostic accuracy of the two available invasive indices of MVR, Dopplerderived hyperaemic microvascular resistance (hMR) versus thermo-dilution-derived index of microcirculatory resistance (IMR), at predicting microvascular dysfunction. We then used the most accurate measure of MVR in Study 2. Study 2. Cold air with and without exercise on MVR in CAD patients. We explored the effects of CAI alone and during exercise on MVR and CBF in patients with significant coronary artery disease. Methods Study 1. 56 patients (61 ± 10 years) undergoing cardiac catheterisation for stable coronary artery disease or acute myocardial infarctions (AMI) were recruited. Simultaneous intracoronary pressure, Doppler flow velocity and thermodilution were carried out in 74 vessels without obstructive epicardial disease, at rest and during hyperaemia. In the absence of a gold-standard, the following three measures of microvascular dysfunction were used, using a pre-defined dichotomous threshold for each parameter: 1) Mean coronary flow reserve (CFRmean), defined as the average value of Doppler and thermodilution derived coronary flow reserve 2) Cardiac Magnetic Resonance (CMR) defined myocardial perfusion reserve index (MPRI) 3) CMR defined extensive microvascular obstruction (MVO). Study 2. 35 patients (62 ± 9 years) with significant coronary artery stenoses who were undergoing coronary angiography were allocated to 5 minutes of either: 1. CAI (-15oC), n=10 2. Exercise (Incremental supine ergometry), n=24 3. Exercise with CAI, n=13. (12 patients did both conditions 2. and 3., and for these patients the order was randomised). Forty seven datasets were obtained in total. We compared rest and peak measurements of Doppler-derived MVR (Pd/CBF) and CBF. We also used wave intensity analysis to identify waves that accelerate and decelerate CBF, and calculated the proportional contribution of accelerating waves as a coronary perfusion efficiency index. Results Study 1. hMR had better diagnostic accuracy than IMR to predict CFRmean (area under curve, (AUC) 0.82 versus 0.58, p < 0.001, sensitivity/specificity 77/77% versus 51/71%) and MPRI (AUC 0.85 versus 0.72, p=0.19, sensitivity/specificity 82/80% versus 64/75%). In AMI patients, the AUCs of hMR and IMR at predicting extensive MVO were 0.83 and 0.72 respectively (p=0.22, sensitivity/specificity 78/74% versus 44/91%). Study 2. MVR increased during CAI alone, whereas MVR decreased during exercise. Exercise with CAI was associated with less decrease in MVR. The increase in CBF was similarly less during exercise with CAI versus without. Coronary perfusion efficiency increased during exercise. However the addition of CAI during exercise abolished this. Conclusion Study 1. In our study cohort Doppler-derived hMR had superior diagnostic accuracy over IMR at predicting several invasive and non-invasive measures of microvascular function. This measure was therefore used to measure MVR in Study 2. Study 2. In CAD patients CAI substantially attenuated the reduction in MVR and the increase in CBF that normally occur during exercise. Moreover, while the heart has improved coronary perfusion efficiency during exercise, this may be attenuated when exercise is combined with CAI. This suggests that CAI during exercise may impede coronary vasodilatation and ventricular relaxation, rendering the heart more susceptible to ischaemia. Complementary studies (Studies 3 and 4) were performed in the absence of invasive measures of central and coronary haemodynamics to examine the differential effects of isometric and dynamic exercise (Study 3) and that of first and second exercise efforts (Study 4).
Supervisor: Redwood, Simon Robert Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available