Invasive physiological stenosis assessment is recommended to identify myocardial ischemia and guide percutaneous coronary intervention (PCI) in patients with stable coronary artery disease (CAD). The therapeutic aims of PCI in stable CAD are to relieve ischemia, resolve angina symptoms and improve exercise capacity. However, the relationship between physiological stenosis severity (i.e. the diagnostic test) and angina-limited exercise capacity (i.e. the therapeutic target) is poorly understood. Accordingly, this represents an important gap in knowledge relevant to the contemporary management of stable CAD.
This gap in knowledge persists because of the lack of physical exercise as an available stressor in the coronary catheter laboratory. However, by use of a catheter laboratory table-mounted supine ergometer, in the series of studies that constitute this thesis, I have been able to invasively characterise systemic, coronary and microcirculatory hemodynamic responses at rest, during pharmacological hyperemia and during maximal physical exercise.
The findings of my thesis are as follows. In Chapter 3 I compare invasive hemodynamic responses to adenosine versus physical exercise stress in patients with stable angina and coronary stenosis. My findings demonstrate that despite the prominent role of adenosine in myocardial ischemia testing, the stress response produced by adenosine is markedly different from physical exercise stress in systemic, coronary and microvascular circulations.
In Chapter 4 I assess the immediate impact of PCI on exercise hemodynamics in patients with stable coronary artery disease. My findings comprehensively characterise the pathophysiology of effort angina. Specifically, I demonstrate that in the presence of a physiologically significant epicardial coronary stenosis, there is failure of augmentation of coronary flow to meet the increasing myocardial oxygen demands of exercise. Mechanistically, this is explained by premature exhaustion of microvascular dilatation with incremental exercise. Conversely, following PCI, by alleviation of stenosis resistance in the epicardial circulation, normal vasodilator capacity of the microcirculation (and thus augmentation of coronary flow) is restored to match increasing myocardial workloads.
In Chapter 5 I demonstrate that an association does indeed exist between physiological stenosis severity and angina-limited exercise time in patients with stable angina. Importantly, I further demonstrate the lack of association between anatomical stenosis severity and angina-limited exercise time. This combination of findings further emphasises the rationale for physiology-guided revascularisation in the contemporary management of stable CAD.
Lastly, from mechanistic insights gained during conduct of this thesis, in Chapter 6, I determine the physiological mechanism of FFR/iFR discordance in stable coronary artery disease – a frequent diagnostic dilemma for the physician. My findings demonstrate that disagreement in ischemia detection between FFR and iFR is explained by differences in hyperemic coronary flow velocity. Specifically, coronary stenoses classified as FFR+/iFR- demonstrate similar coronary flow characteristics to both FFR-/iFR- and angiographically unobstructed vessels.