Model prediction of subendocardial perfusion of the coronary circulation in the presence of an epicardial coronary artery stenosis

The subendocardium is most vulnerable to ischemia, which is ameliorated by relaxation during diastole and increased coronary pressure. Recent clinical techniques permit the measuring of subendocardial perfusion and it is therefore important to gain insight into how measurements depend on perfusion conditions of the heart. Using data from microsphere experiments a layered model of the myocardial wall was developed. Myocardial perfusion distribution during hyperemia was predicted for different degrees of coronary stenosis and at different levels of Diastolic Time Fraction (DTF). At the reference DTF, perfusion was rather evenly distributed over the layers and the effect of the stenosis was homogenous. However, at shorter or longer DTF, the subendocardium was the first or last to suffer from shortage of perfusion. It is therefore concluded that the possible occurrence of subendocardial ischemia at exercise is underestimated when heart rate is increased and DTF is lower

Coronary microvascular resistance: methods for its quantification in humans

Coronary microvascular dysfunction is a topic that has recently gained considerable interest in the medical community owing to the growing awareness that microvascular dysfunction occurs in a number of myocardial disease states and has important prognostic implications. With this growing awareness, comes the desire to accurately assess the functional capacity of the coronary microcirculation for diagnostic purposes as well as to monitor the effects of therapeutic interventions that are targeted at reversing the extent of coronary microvascular dysfunction. Measurements of coronary microvascular resistance play a pivotal role in achieving that goal and several invasive and noninvasive methods have been developed for its quantification. This review is intended to provide an update pertaining to the methodology of these different imaging techniques, including the discussion of their strengths and weaknesses

Modeling left ventricle perfusion in healthy and stenotic conditions

A theoretical fluid mechanical model is proposed for the investigation of myocardial perfusion in healthy and stenotic conditions. The model hinges on Terzaghi’s consolidation theory and reformulates the related unsteady flow equation for the simulation of the swelling–drainage alternation characterizing the diastolic–systolic phases. When compared with the outcome of experimental in vivo observations in terms of left ventricle transmural perfusion ratio (T.P.R.), the analytical solution provided by the present study for the time-dependent blood pressure and flow rate across the ventricle wall proves to consistently reproduce the basic mechanisms of both healthy and ischemic perfusion. Therefore, it could constitute a useful interpretative support to improve the comprehension of the basic hemodynamic mechanisms leading to the most common cardiac diseases. Additionally, it could represent the mathematical basis for the application of inverse methods aimed at estimating the characteristic parameters of ischemic perfusion (i.e., location and severity of coronary stenoses) via downstream ventricular measurements, possibly inspiring their assessment via non-invasive myocardial imaging techniques

Cardiovascular Magnetic Resonance Myocardial Perfusion Mapping for the Assessment of Coronary Artery Disease

Pixelwise myocardial perfusion mapping is a novel cardiovascular magnetic resonance (CMR) technique enables quantitative measurement of myocardial blood flow (MBF) at a pixel level. This could improve the accuracy of detection of obstructive coronary artery disease (CAD) and may also have a role in the diagnosis and assessment of coronary microvascular dysfunction (CMD). In this thesis, I explore the use of this novel technique in cohorts of clinical patients and controls with suspected CAD or CMD. Firstly, I demonstrate that stress MBF measured using perfusion mapping is accurate for the detection of CAD using invasive fractional flow reserve (FFR) as the reference standard, and that global stress MBF can be used as a marker of CMD using invasive index of microcirculatory resistance (IMR) as the reference standard. One limitation of adenosine stress testing is the confirmation of adequate hyperaemia with lack of gold standard non-invasive marker. Here, I demonstrate that regional stress MBF can be utilised as a non-invasive marker of adequate stress response. Another limitation of stress MBF is the relatively poor performance for the detection of multivessel disease. In a cohort of patients with confirmed two- and three-vessel disease I demonstrate that perfusion mapping is superior to visual analysis for the correct identification of disease severity. Perfusion mapping provides a host of options for quantitative image analysis. I show that the most reliable method for detection of coronary disease at a patient level is the presence of reduced MBF in two adjacent myocardial segments. In summary, in this thesis I performed a series of studies investigating the clinical utilisation of CMR perfusion mapping that can be translated to clinical practice to enhance the performance of stress perfusion CMR

Myocardial first-pass perfusion cardiovascular magnetic resonance: history, theory, and current state of the art

In less than two decades, first-pass perfusion cardiovascular magnetic resonance (CMR) has undergone a wide range of changes with the development and availability of improved hardware, software, and contrast agents, in concert with a better understanding of the mechanisms of contrast enhancement. The following review provides a perspective of the historical development of first-pass CMR, the developments in pulse sequence design and contrast agents, the relevant animal models used in early preclinical studies, the mechanism of artifacts, the differences between 1.5T and 3T scanning, and the relevant clinical applications and protocols. This comprehensive overview includes a summary of the past clinical performance of first-pass perfusion CMR and current clinical applications using state-of-the-art methodologies

The effect of coronary calcifications on interpretation of non-invasive investigations for coronary artery disease in patients with typical chest pain

Coronary artery disease (CAD) is the most common cause of mortality. Invasive coronary angiography remains the gold standard for the diagnosis of patients with stable CAD and acute coronary syndromes (ACS). However, the accurate diagnosis of CAD is complex and may involve a number of different investigations, including non-invasive techniques, primarily based on patient symptoms. The aim of this thesis was to investigate the prediction of CAD from coronary calcium scoring using multi-detector computed tomography (MDCT) against exercise treadmill testing (ETT [n=360]), myocardial perfusion imaging using magnetic resonance imaging (CMR [n=120]), and myocardial ischaemia assessed using Dobutamine stress echocardiography (DSE [n=35]) in a retrospective cohort of patients with typical chest pain. All 515 patients underwent conventional coronary angiography within 1-month of their non-invasive investigations. The results of this thesis demonstrated that MDCT is more accurate than ETT in identifying significant CAD, whereas a negative ETT was accurate in excluding CAD, as such the two investigations are complementary. Compared to CMR, MDCT was more accurate in detecting significant CAD. However, the burden of perfusion defects during stress was associated with a progressive increase in CAC in patients with non-obstructive CAD only. Finally, DSE was abnormal in patients with non-significant coronary stenosis but with high CAC and a positive ETT, which may suggest microvascular disease. In addition, resting wall motion abnormalities on echocardiography was associated with coronary calcification by MDCT. Non-invasive techniques for the assessment, diagnosis and treatment of CAD remains an integral component for the investigation of chest pain. Future research is required to investigate the relative importance of non-invasive assessments of CAD with respect to coronary intervention, adverse cardiovascular outcomes and all-cause mortality

Rationale and design of the Coronary Microvascular Angina Cardiac Magnetic Resonance imaging (CorCMR) diagnostic study: the CorMicA CMR sub-study

Introduction: Angina with no obstructive coronary artery disease (ANOCA) is a common syndrome with unmet clinical needs. Microvascular and vasospastic angina are relevant but may not be diagnosed without measuring coronary vascular function. The relationship between cardiovascular magnetic resonance (CMR)-derived myocardial blood flow (MBF) and reference invasive coronary function tests is uncertain. We hypothesise that multiparametric CMR assessment will be clinically useful in the ANOCA diagnostic pathway. Methods/analysis: The Stratified Medical Therapy Using Invasive Coronary Function Testing In Angina (CorMicA) trial is a prospective, blinded, randomised, sham-controlled study comparing two management approaches in patients with ANOCA. We aim to recruit consecutive patients with stable angina undergoing elective invasive coronary angiography. Eligible patients with ANOCA (n=150) will be randomised to invasive coronary artery function-guided diagnosis and treatment (intervention group) or not (control group). Based on these test results, patients will be stratified into disease endotypes: microvascular angina, vasospastic angina, mixed microvascular/vasospastic angina, obstructive epicardial coronary artery disease and non-cardiac chest pain. After randomisation in CorMicA, subjects will be invited to participate in the Coronary Microvascular Angina Cardiac Magnetic Resonance Imaging (CorCMR) substudy. Patients will undergo multiparametric CMR and have assessments of MBF (using a novel pixel-wise fully quantitative method), left ventricular function and mass, and tissue characterisation (T1 mapping and late gadolinium enhancement imaging). Abnormalities of myocardial perfusion and associations between MBF and invasive coronary artery function tests will be assessed. The CorCMR substudy represents the largest cohort of ANOCA patients with paired multiparametric CMR and comprehensive invasive coronary vascular function tests. Ethics/dissemination: The CorMicA trial and CorCMR substudy have UK REC approval (ref.16/WS/0192). Trial registration number: NCT03193294