Coronary Angiography

In the intervening 10 years tremendous advances in the field of cardiac computed tomography have occurred. We now can legitimately claim that computed tomography angiography (CTA) of the coronary arteries is available. In the evaluation of patients with suspected coronary artery disease (CAD), many guidelines today consider CTA an alternative to stress testing. The use of CTA in primary prevention patients is more controversial in considering diagnostic test interpretation in populations with a low prevalence to disease. However the nuclear technique most frequently used by cardiologists is myocardial perfusion imaging (MPI). The combination of a nuclear camera with CTA allows for the attainment of coronary anatomic, cardiac function and MPI from one piece of equipment. PET/SPECT cameras can now assess perfusion, function, and metabolism. Assessing cardiac viability is now fairly routine with these enhancements to cardiac imaging. This issue is full of important information that every cardiologist needs to now

Characterization, prevalence, and risk factors of spontaneous and experimental atherosclerosis and vascular imaging in psittaciformes

Atherosclerosis is a degenerative and inflammatory vascular disease characterized by the accumulation of inflammatory cells, lipids, calcium, and formation of large fibrofatty lesions within the intima of arteries resulting in the disorganization of the arterial wall and stenosis of the lumen. Despite the importance of atherosclerosis in psittacine cardiology, there are few pathologic, clinical, and experimental investigations in psittaciformes. In order to expand the knowledge on psittacine atherosclerosis and provide fundamental observational information for future research, a series of studies was conducted on psittaciformes: 1) psittacine atherosclerotic lesions were characterized and categorized based on histopathology, histochemistry, transmission (TEM), and scanning electron microscopy (SEM) of 63 arterial samples, 2) the prevalence of clinically significant atherosclerotic lesions and the influence of several epidemiological variables were investigated in a multi-center case-control study on 7683 psittaciformes, 3) a diet-induced experimental model of atherosclerosis was developed and characterized in Quaker parrots (Myiopsitta monachus), and 4) a computed-tomography angiographic (CTA) protocol was developed and standardized to image the arterial lumen in Hispaniolan Amazon parrots (Amazona ventralis). Seven lesion types could be described in psittaciformes, which were similar to the human classification system. Digital image analysis, TEM, and SEM helped to further describe the lesions and refine the classification system. Atherosclerosis prevalence significantly increased with age, female sex, and the genera Psittacus, Amazona, and Nymphicus. Mild associations with reproductive, hepatic diseases, and myocardial fibrosis were also evidenced. Experimental induction of atherosclerosis with dietary 1% cholesterol lead to significant lesions within 2 months in Quaker parrots. An increase in arterial and plasma cholesterol and LDL was also documented. Reference limits for arterial luminal diameter of Hispaniolan Amazon parrots were determined by CTA and measurements revealed high intraobserver and interobserver agreement. In conclusion, psittacine atherosclerotic lesions displayed distinctive features that allowed the development of an effective classification system. The prevalence of advanced lesions (type IV-VI) was associated with several risk factors: age, female sex, and three psittacine genera. The Quaker parrot was found to be a suitable experimental model for psittacine atherosclerosis and dyslipidemia. Finally CTA was determined to be safe, reliable, and of potential diagnostic value in parrots for diagnosing stenotic atherosclerotic lesions

Medical imaging of the heart :quantitative analysis of three-dimensional echocardiographic images

PhD ThesisAccurate, reproducible determination of cardiac chamber volume, especially left ventricular (LV) volume, is important for clinical assessment, risk stratification, selection of therapy, and serial monitoring of patients with cardiovascular disease. Echocardiography is the most widely used imaging modality in the clinical diagnosis of left ventricular function abnormalities. In the last 15 years, developments in real time three-dimensional echocardiography (RT3DE) have achieved superior accuracy and reproducibility compared with conventional two-dimensional echocardiography (2DE) for measurement of left ventricular volume and function. However, RT3DE suffers from the limitations inherent to the ultrasonic imaging modality and the cost of increased effort of data handling and image analysis. There were two aims of this research project. Firstly, it aimed to develop different new semi-automated algorithms for LV endocardial surface delineation, LV volume and EF quantification from clinical RT3DE images. Secondly, through assessing and comparing the performance of these algorithms in the aspects of accuracy and reproducibility, this project aimed to investigate what factors in real time 3D echo images influenced the performance of each algorithm, so that advantages and drawbacks of 3D echo images can be better understood. The basic structure of the content of this thesis is as follows: Chapter 1 introduces the background and the aims of this project. Chapter 2 describes the development of the new semi-automated algorithms. Chapter 3 to Chapter 6 presents the four studies designed to assess and compare the accuracy and reproducibility of each algorithm. These studies were the balloon phantom study, the tissue-mimicking phantom study, the clinical cardiac magnetic resonance images study and the clinical contrast enhanced 3D stress echo images study. Chapter 7 summarises all these studies, draws conclusions, and describes future work. In conclusion, it has been shown that the semi-automated algorithms can measure LV volume and EF quantitatively in clinical 3D echo images. To achieve better accuracy and reproducibility, 3D echo images should be analysed from all three dimensions

Tailored reperfusion therapy of patients with evolving myocardial infarction: Models to guide clinical decision making

Myocardial infarction is one of the leading causes of death among adults in the Western World. In The Netherlands, yearly approximately 20,000 men and 10,000 women are admitted with this diseas

The stress radionuclide assessment of diastolic function

Background Many patients are referred from primary care with suspected heart failure and are found to have preserved systolic function. These patients may be labelled as having normal ejection fraction or diastolic heart failure, the diagnosis of which is both controversial and difficult. Previous work has identified a large proportion of these patients to have an alternative, pre- existing diagnosis. This thesis prospectively assesses the prevalence of undiagnosed ischaemic heart disease and respiratory disease in this patient group and assess diastolic function using multiple methods. The central hypothesis being tested was that first third fractional filling, a radionuclide ventriculogram (RNVG) parameter previously used to assess diastolic function at rest, would identify diastolic dysfunction more accurately under stress conditions. Methods Patients were recruited from an open access echocardiography service. Echocardiography, including tissue Doppler assessment, was carried out independently by 2 experienced observers. Confounding diagnoses including coronary artery disease and respiratory disease were actively sought by myocardial perfusion imaging and spirometry. N-terminal proBNP was measured. List mode radionuclide ventriculography was performed at rest supine and during upright bicycle exercise with simultaneous measurement of VO2 max. Validation of the reliability and reproducibility of first third fractional filling, peak filling rate, time to peak filling and other radionuclide parameters of systolic and diastolic function was undertaken. This demonstrated that it was possible to measure both first third fractional filling and peak filling rate with the short acquisition times necessary for assessment during stress. Time to peak filling was poorly reproducible under these conditions. A normal range for first third fractional filling at rest and during exercise was established. Due to a strong inverse relationship between heart rate and first third fractional filling, a continuous reference range was constructed using an exponential model. This unique approach enables the calculation of the lower limit of normal at any heart rate. A more conventional mean ± 2 standard deviations was used for the other RNVG parameters. Results Eighty three patients were recruited and completed an extensive multi-modality assessment of systolic and diastolic function. As with previous work in this field, the patients were predominantly female (82%) and elderly (mean age 66.7). Mild left ventricular systolic dysfunction as determined by RNVG was missed by echocardiography in one third of patients. Systolic dysfunction more significant than this was not observed. N-terminal proBNP was elevated in 21 of 82 patients where it was available with no significant difference in left ventricular ejection fraction between those with normal and elevated levels. Myocardial perfusion scanning was normal in 46 of 83 patients and showed significant ischaemia in 20 of 83. Spirometry was normal in 58 of 82 patients, with mild airflow obstruction in 20 patients and moderate obstruction in 4. In only one patient were no alternative diagnoses present. There was poor correlation between indices of diastolic function at rest including first third fractional filling, echocardiographic parameters and NT-proBNP. The assessment of diastolic function using stress radionuclide ventriculography did not improve the correlation between measured indices. On stress, however, low first third fractional filling predicted exercise intolerance as an inability to reach anaerobic threshold. Conclusions Alternative diagnoses to diastolic dysfunction are present almost universally in patients with suspected normal ejection fraction heart failure. This is true even where these diagnoses are not previously established. This thesis underlines the need to fully assess this patient group to allow appropriate targeting of therapy. It is also clear that echocardiography alone is potentially misleading and it is suggested that it is better placed within a tiered assessment process. The assessment of diastolic function using stress radionuclide ventriculography, although an appealing concept, does not improve diagnostic accuracy within this patient group. The marked heterogeneity of this patient group is likely to have played a role in this and it may be of interest to reassess stress radionuclide ventriculography in a more acute heart failure population

Non-Invasive Venous Thrombus Composition and Therapeutic Response by Multiparametric MRI

Deep vein thrombosis (DVT), or a blood clot in a deep vein (commonly the legs), is known as the silent killer—there may be few or no symptoms, yet a section of the thrombus could break free and travel to the lungs causing a potentially fatal pulmonary embolism. DVT and its complications affect 900,000 people in the U.S. each year, with one third of cases resulting in fatality. Anticoagulants (the standard treatment) pose serious bleeding risks and rely on the patient’s fibrinolytic system to break up the thrombus, which is often incapable of doing so thus leading to post thrombotic syndrome (PTS) in almost 50% of patients. Removing the DVT completely via thrombolytic treatments may improve quality of life by reducing PTS. However, thrombolysis is only effective on acute thrombi. Impaired success with thrombolytic treatment is due to heterogeneity in the thrombus (old clot, which is unable to be broken up, intermixed with fresh clot, which can easily be broken up). This problem is largely overlooked based on an inability to determine thrombus composition. Currently, the only method for determining disease stage is the patient’s recollection of when their symptoms began, which is inherently unreliable and could put the patient at risk. Further, thrombi of the same chronological age may organize at different rates in different people. Magnetic resonance imaging (MRI) has the potential to provide information about thrombus composition (clot age), and thus inform patient-specific treatment planning. Since there are several limitations to studying DVT in humans, animal models are key tools for understanding the disease. Mouse models are the most commonly used, providing a unique biological environment to study disease progression and treatment. Any model requires rigorous characterization and standardization to ensure reproducibility between studies. Our first objective was to quantify structural and functional changes in the healthy venous system of young and aged mice of both sexes, at rest and under conditions which simulate exercise. Second, we assessed the endogenous response to two models of DVT mimicking the two possible clinical scenarios: total or partial occlusion. Following the necessary model characterization, we developed a multiparametric MRI approach to probe thrombus composition without the need for contrast agents. Our results show imaging correlation with known composition by histology. This method provides a novel approach to study thrombus composition, and could eventually be used clinically to provide patient-specific treatment planning for DVT. Additionally, we investigated the impact of exercise, an emerging therapeutic option, on thrombus composition. Using an in-cage running wheel, our results show that spontaneous exercise – both alone and in combination with standard treatment – reduces initial thrombus size and contributes to thrombus resolution. We found that exercise increases acute fibrin content, attenuates local inflammation, and decreases sub-chronic collagen content in pharmacologically treated mice. This work provides 1) the first in vivo characterization of the murine venous system in health and disease, 2) a foundational methodology to determine thrombus composition by MRI, and 3) insights on the impact of exercise on DVT. This research can help DVT investigators from the animal model perspective, and provides a step forward in characterizing thrombus composition for patient-specific DVT treatment planning.PHDBiomedical EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttps://deepblue.lib.umich.edu/bitstream/2027.42/149918/1/opalmer_1.pd

Computational Modelling in the Management of Patients with Aortic Valve Stenosis

Background Stenosis of the aortic valve causes increased left ventricular pressure leading to adverse clinical outcomes. The selection and timing of intervention (surgical replacement or transcatheter implantation) is often unclear and is based upon limited data. Hypothesis A comprehensive and integrated personalised approach, including recognition of cardiac energetics parameters extracted from a personalised mathematical model, mapped to patient activity, has the potential to improve diagnosis and the planning and timing of interventions. Aims This project seeks to implement a simple, personalised, mathematical model of patients with aortic stenosis (AS), which can ‘measure’ cardiac work and power parameters that provide an effective characterisation of the demand on the heart in both rest and exercise conditions and can predict the changes of these parameters following an intervention. The specific aims of this project are: • to critically review current diagnostic methods • to evaluate the potential role of pre- and post-procedural measured patient activity • to implement a simple, personalised, mathematical model of patients with AS • to evaluate the potential role of a clinical decision support system Methods Twenty-two patients with severe AS according to ESC criteria were recruited. Relevant clinical, imaging, activity monitoring, six-minute walk test, and patient reported data were collected, before and early and after treatment. Novel imaging techniques were developed to help in the diagnosis of AS. A computational model was developed and executed using the data collected to create non-invasive pressure volume loops and study the global haemodynamic burden on the left ventricle. Simulations were run to predict the haemodynamic parameters both during exercise and following intervention. Modelled parameters were validated against clinically measured values. This information was then correlated with symptoms and activity data. A clinical decision support tool was created and populated with data obtained and its clinical utility evaluated. Outcomes The results of this project suggest that the combination of imaging and activity data with computational modelling provides a novel, patient-specific insight into patients’ haemodynamics and may help guide clinical decision making in patients with AS

Model-based quantification of systolic and diastolic left ventricular mechanics

Het linker ventrikel (LV) is de meest gespierde kamer van het hart. Door het gecoördineerd samentrekken van de spiercellen in de LV-wand wordt zuurstofrijk bloed in de aorta gepompt (systolische fase). Daarna ontspannen de spiercellen zich snel waardoor het LV opnieuw met bloed wordt gevuld (diastolische fase). In de kliniek en de onderzoekswereld bestaat er een waaier van modelgebaseerde methoden en concepten om de performantie en de mechanische eigenschappen van het LV te kwantificeren. Invasief bekomen druk- en volumedata laten toe om de systolische en diastolische mechanica van het LV met grote nauwkeurigheid te kennen. In de klinische praktijk wordt echter vaker gebruik gemaakt van (Doppler-) echocardiografie, een snelle en veilige niet-invasieve beeldtechniek. In een eerste deel van dit doctoraatsonderzoek werd een originele methode voorgesteld om, op basis van echocardiografie en klassieke bloeddrukmetingen, de intrinsieke krachtontwikkeling (contractiliteit) van het LV te schatten. De methode werd toegepast bij 2524 mensen die deelnemen aan de Asklepios-studie. De onderzoeksresultaten verschaften ons nieuwe informatie over hoe de evolutie van de krachtontwikkeling verschilt tussen gezonde mannen en vrouwen. De mechanische en vloeistofdynamische fenomenen tijdens de diastole vormden het onderwerp van het tweede deel van het onderzoek. Met behulp van een hydraulisch model van het LV werd nagegaan welke factoren een belangrijke invloed uitoefenen op het gedrag van het LV tijdens de isovolumetrische ontspanningsfase. In dit deel werd eveneens een uitgebreid overzicht gegeven van de meest recente echocardiografische methoden om de diastolische LV-mechanica te begroten. Daarbij werden de bloedstroming, de wandbeweging en de interactie tussen beiden gedetailleerd behandeld