Mhairi K. Doris

Imaging of coronary atherosclerosis — evolution towards new treatment strategies

Coronary atherosclerosis and the precipitation of acute myocardial infarction are highly complex processes, which makes accurate risk prediction challenging. Rapid developments in invasive and noninvasive imaging technologies now provide us with detailed, exquisite images of the coronary vasculature that allow direct investigation of a wide range of these processes. These modalities include sophisticated assessments of luminal stenoses and myocardial perfusion, complemented by novel measures of the atherosclerotic plaque burden, adverse plaque characteristics, and disease activity. Together, they can provide comprehensive, individualized assessments of coronary atherosclerosis as it occurs in patients. Not only can this information provide important pathological insights, but it can also potentially be used to guide personalized treatment decisions. In this Review, we describe the latest advances in both established and emerging imaging techniques, focusing on the strengths and weakness of each approach. Moreover, we discuss how these technological advances might be translated from attractive images into novel imaging strategies and definite improvements in clinical risk prediction and patient outcomes. This process will not be easy, and the many potential barriers and difficulties are also reviewed.

Coronary CT Angiography as a Diagnostic and Prognostic Tool: Perspectives from the SCOT-HEART Trial

Coronary artery disease is the leading cause of death worldwide. Many trials to date have investigated the diagnostic accuracy of coronary computed tomography angiography (CCTA) when compared to the gold standard diagnostic test, invasive coronary angiography. However, whether the use of a non-invasive anatomical test, such as CCTA, can translate into improved patient risk stratification, management and outcome has yet to be established. The Scottish COmputed Tomography of the HEART (SCOT-HEART) trial sought to address these questions and determined whether CCTA, when used in addition to standard care, could aid the diagnosis, further investigation and treatment of patients referred to the cardiology clinic with suspected angina due to coronary heart disease. In this trial, CCTA clarified the diagnosis of angina due to coronary heart disease in a quarter of patients and this led to major alterations in treatment and management that appeared to reduce the risk of subsequent coronary heart disease death or non-fatal myocardial infarction. The SCOT-Heart trial has established that CCTA is a valuable diagnostic test in patients with suspected angina pectoris due to coronary heart disease and leads to greater clarity, more focused appropriate treatments and better coronary heart disease outcomes.

Enhancing Cardiac PET by Motion Correction Techniques

Purpose of ReviewCardiac positron emission tomography (PET) images often contain errors due to cardiac, respiratory, and patient motion during relatively long image acquisition. Advanced motion compensation techniques may improve PET spatial resolution, eliminate potential artifacts, and ultimately improve the research and clinical capabilities of PET.Recent FindingsCombined cardiac and respiratory gating has only recently been implemented in clinical PET systems. Considering that the gated image bins contain much lower counts than the original PET data, they need to be summed after correcting for motion, forming motion-corrected, high-count image volume. Furthermore, automated image registration techniques can be used to correct for motion between CT attenuation scan and PET acquisition.SummaryWhile motion correction methods are not yet widely used in clinical practice, approaches including dual-gated non-rigid motion correction and the incorporation of motion correction information into the reconstruction process have the potential to markedly improve cardiac PET imaging.

Motion-corrected imaging of the aortic valve with (18)F-NaF PET/CT and PET/MR: a feasibility study

We investigated whether motion correction of gated 18F-fluoride PET/CT and PET/MRI of the aortic valve could improve PET quantitation and image quality. Methods: A diffeomorphic, mass-preserving, anatomy-guided registration algorithm was used to align the PET images from 4 cardiac gates, preserving all counts, and apply them to the PET/MRI and PET/CT data of 6 patients with aortic stenosis. Measured signal-to-noise ratios (SNRs) and target-to-background ratios (TBRs) were compared with the standard method of using only the diastolic gate. Results: High-intensity aortic valve 18F-fluoride uptake was observed in all patients. After motion correction, SNR and TBR increased compared with the median diastolic gate (SNR, 51.61 vs. 21.0; TBR, 2.85 vs. 2.22) and the median summed data (SNR, 51.61 vs. 34.10; TBR, 2.85 vs. 1.95) (P = 0.028 for all). Furthermore, noise decreased from 0.105 (median, diastolic) to 0.042 (median, motion-corrected) (P = 0.028). Conclusion: Motion correction of hybrid 18F-fluoride PET markedly improves SNR, resulting in improved image quality.

Molecular Imaging of Vulnerable Coronary Plaque: A Pathophysiologic Perspective

Atherothrombotic events in coronary arteries are most often due to rupture of unstable plaque resulting in myocardial infarction. Radiolabeled molecular imaging tracers directed toward cellular targets that are unique to unstable plaque can serve as a powerful tool for identifying high-risk patients and for assessing the potential of new therapeutic approaches. Two commonly available radiopharmaceuticals—18F-FDG and 18F-NaF—have been used in clinical research for imaging coronary artery plaque, and ongoing clinical studies are testing whether there is an association between 18F-NaF uptake and future atherothrombotic events. Other, less available, tracers that target macrophages, endothelial cells, and apoptotic cells have also been tested in small groups of patients. Adoption of molecular imaging of coronary plaque into clinical practice will depend on overcoming major hurdles, ultimately including evidence that the detection of unstable plaque can change patient management and improve outcomes.

How should CT coronary angiography be integrated into the management of patients with chest pain and how does this affect outcomes

Abstract When examining the role of a diagnostic test in clinical practice, consideration must be placed not only on the accuracy of the result, but also its impact on patient care and outcomes. Proving a direct effect on outcomes may be difficult because the impact of the diagnostic test largely depends on the clinicians interpretation and consequent actions as well as the patients response to changes in their diagnosis, investigations, and treatment. Recent major clinical trials of symptomatic patients with suspected coronary heart disease (CHD) have shown that computed tomography coronary angiography (CTCA) can markedly clarify the diagnosis and lead to major changes in patient investigation and management including the use of invasive angiography, preventative therapies, and coronary revascularization. Thus, when added to our existing clinical tools, such as exercise electrocardiography, CTCA represents a powerful method of identifying and excluding CHD. Furthermore, it can identify patients with prognostically relevant non-obstructive CHD and, with recent technological advances, will be able to assess the functional impact of anatomically detected coronary artery stenoses. Overall, the routine integration of CTCA into the investigation of patients with chest pain improves clinical diagnostic certainty that has led to better targeting of investigations and evidence-based treatments that have ultimately translated into improved clinical outcomes.

The future of imaging in cardiovascular disease intervention trials: 2017 and beyond.

Purpose of review As our understanding of cardiovascular disease has advanced over the past decades, multiple novel treatment strategies have been developed with the hope of reducing the global morbidity and mortality associated with this condition. Large-scale trials to test such novel therapies using clinical end points are expensive, leading to interest in phase II clinical trials with imaging-derived outcome measures. Recent findings Noninvasive imaging techniques that assess changes in both atherosclerotic disease burden and plaque composition in response to therapy are well established. With the advent of molecular techniques and hybrid imaging, we now have the ability to assess disease activity alongside these standard anatomic assessments. This multifaceted approach has the potential to provide a more comprehensive assessment of the actions and efficacy of novel therapies in the carotids, aorta and coronary arteries. Summary This review will examine how advanced noninvasive imaging strategies have been used to investigate drug efficacy in intervention trials to date, and crucially how these approaches are set to evolve and play a central role in developing the next generation of atherosclerotic medication.

HORMONE REPLACEMENT THERAPY IS ASSOCIATED WITH LESS CORONARY ATHEROSCLEROSIS AND LOWER MORTALITY

Background: There is a controversy regarding the role of hormone replacement therapy (HRT) as a cardio-protective agent in postmenopausal women. We aim to examine the effect of HRT treatment on coronary artery calcium (CAC) and on mortality in a large retrospective cohort of post-menopausal women

Non-invasive fractional flow reserve in vessels without severe obstructive stenosis is associated with coronary plaque burden

AIMS Non-invasive fractional flow reserve derived from coronary CT angiography (FFRCT) has been shown to be predictive of lesion-specific ischemia as assessed by invasive fractional flow reserve (FFR). However, in practice, clinicians are often faced with an abnormal distal FFRCT in the absence of a discrete obstructive lesion. Using quantitative plaque analysis, we sought to determine the relationship between an abnormal whole vessel FFRCT (V-FFRCT) and quantitative measures of whole vessel atherosclerosis in coronary arteries without obstructive stenosis. METHODS FFRCT was calculated in 155 consecutive patients undergoing coronary CTA with ≥25% but less than 70% stenosis in at least one major epicardial vessel. Semi-automated software was used to quantify plaque volumes (total plaque [TP], calcified plaque [CP], non-calcified plaque [NCP], low-density non-calcified plaque [LD-NCP]), remodeling index [RI], maximal contrast density difference [CDD] and percent diameter stenosis [%DS]. Abnormal V-FFRCT was defined as a minimum value of ≤0.75 across the vessel (at the most distal region where FFRCT was computed). RESULTS Vessels with abnormal V-FFRCT had higher per-vessel TP (554 vs 331 mm3), CP (59 vs 25 mm3), NCP (429 vs 295 mm3), LD-NCP (65 vs 35 mm3) volume and maximum CDD (21 vs 14%) than those with normal V-FFRCT (median, p < 0.05 for all). Using a multivariate analysis to adjust for CDD and %DS, all measures of plaque volume were predictive of abnormal V-FFRCT (OR 2.09, 1.36, 1.95, 1.95 for TP, CP, NCP and LD-NCP volume, respectively; p < 0.05 for all). CONCLUSION Abnormal V-FFRCT in vessels without obstructive stenosis is associated with multiple markers of diffuse non-obstructive atherosclerosis, independent of stenosis severity. Whole vessel FFRCT may represent a novel measure of diffuse coronary plaque burden.

18 18F-flouride pet MR in valvular and coronary heart disease; a pilot investigational study

Introduction Recently, PET-MR has emerged as a novel imaging technique capable of assessing myocardial disease, inflammation and microcalcification. We aimed to investigate aortic valve and coronary 18F-NaF activity in subjects with aortic stenosis (AS) and coronary disease. Methods 25 patients underwent 18F-NaF PET-MR scanning. PET data was acquired in list mode with a standard Dixon attenuation correction technique. MR angiography was performed following infusion of Gadolinium. PET activity was quantified by calculating standardised uptake values (SUV) and tissue to background ratios (TBR) on fused PET-MR images. Culprit arteries were identified during preceding invasive coronary angiography. Results 22 of 25 patients completed the protocol. Patients with aortic stenosis had higher aortic valve SUVmax and TBRmax (Valve SUV max/left atrial SUV mean) than those without (SUVmax 1.89±0.60 vs 1.15±0.38, p=0.001 and TBRmax 2.87±0.98 vs 1.77±0.43, p=0.001). 13/13 patients with MI had focal 18F-NaF uptake in the culprit vessel with an SUV max and TBR max greater than the proximal referent vessel (SUV max 1.05±0.26 vs 0.74±0.13, p=0.002 and TBRmax 1.64±0.47 vs 1.16±0.26, p=0.004). Conclusion Similar to previous 18F-NaF PET CT studies, 18F-NaF PET-MR uptake is significantly greater in those with confirmed AS than those without. 18F-NaF uptake also accurately identifies culprit arteries in those with recent MI. The results share similarities with recently published valvular and coronary 18F-NaF PET-CT studies and thus promote further research into the utility of cardiovascular PET-MR as a complementary hybrid imaging technique.