Coronary Imaging Studies Research Articles

Noninvasive Plaque Imaging to Accelerate Coronary Artery Disease Drug Development.

Coronary artery disease (CAD) remains the leading cause of adult mortality globally. Targeting known modifiable risk factors has had substantial benefit, but there remains a need for new approaches. Improvements in invasive and noninvasive imaging techniques have enabled an increasing recognition of distinct quantitative phenotypes of coronary atherosclerosis that are prognostically relevant. There are marked differences in plaque phenotype, from the high-risk, lipid-rich, thin-capped atheroma to the low-risk, quiescent, eccentric, nonobstructive calcified plaque. Such distinct phenotypes reflect different pathophysiologic pathways and are associated with different risks for acute ischemic events. Noninvasive coronary imaging techniques, such as computed tomography, positron emission tomography, and coronary magnetic resonance imaging, have major potential to accelerate cardiovascular drug development, which has been affected by the high costs and protracted timelines of cardiovascular outcome trials. This may be achieved through enrichment of high-risk phenotypes with higher event rates or as primary end points of drug efficacy, at least in phase 2 trials, in a manner historically performed through intravascular coronary imaging studies. Herein, we provide a comprehensive review of the current technology available and its application in clinical trials, including implications for sample size requirements, as well as potential limitations. In its effort to accelerate drug development, the US Food and Drug Administration has approved surrogate end points for 120 conditions, but not for CAD. There are robust data showing the beneficial effects of drugs, including statins, on CAD progression and plaque stabilization in a manner that correlates with established clinical end points of mortality and major adverse cardiovascular events. This, together with a clear mechanistic rationale for using imaging as a surrogate CAD end point, makes it timely for CAD imaging end points to be considered. We discuss the importance of global consensus on these imaging end points and protocols and partnership with regulatory bodies to build a more informed, sustainable staged pathway for novel therapies.

Identifying Subclinical Coronary Abnormalities and Silent Myocardial Ischemia After Arterial Switch Operation.

The incidence of late coronary complications is reported around 8% after arterial switch operation (ASO) for d-transposition of the great arteries, but the affected patients are usually asymptomatic. Exercise stress test (EST) and myocardial perfusion imaging (MPI) are common non-invasive modalities to screen for silent myocardial ischemia, but their diagnostic reliability in children after ASO is unclear. We retrospectively reviewed asymptomatic patients following ASO with EST, MPI, and coronary imaging studies (CIS) and examined the reliability of each test in identifying abnormal coronary lesions responsible for myocardial ischemia. Thirty-seven asymptomatic patients (24 males; ages 12.7 ± 3.7years) had EST, in which 27 and 33 patients also underwent MPI and CIS, respectively. Exercise capacity was comparable to the age- and sex-matched 37 controls. In seven patients with angiographically proven moderate to severe coronary abnormalities, only two patients had positive EST and/or MPI, and five patients were negative including one patient who later developed exercise-induced cardiac arrest due to severe proximal left coronary artery stenosis. Two patients with positive EST or MPI showed no correspondingcoronary abnormalities by CIS. Occurrence of acquired late coronary abnormalities did not correlate with the original coronary anatomy or initial surgical procedures. There is no single reliable method to identify the risk of myocardial ischemia after ASO. Although CIS are regarded as a gold standard, multidisciplinary studies are essential to risk-stratify the potential life-threatening coronary lesions after ASO in children.

Obstructive sleep apnoea and coronary artery disease.

Obstructive sleep apnoea (OSA) is a highly prevalent disorder, which causes significant nocturnal and daytime symptoms, reduced quality of life, and impaired functional capacity. Importantly, however, OSA also appears to predispose to the development of a number of cardiovascular and metabolic diseases, including diabetes, hypertension, and stroke. In this review we explore its relationship with coronary artery disease (CAD), discussing mechanisms whereby it may promote the development of atherosclerosis, evidence of its effect on CAD incidence and outcomes, and coronary imaging studies in subjects with OSA. Finally, we shall evaluate the current evidence regarding the impact of continuous positive airway pressure therapy on CAD outcomes in OSA patients.

Severity of obstructive sleep apnoea predicts coronary artery plaque burden: a coronary computed tomographic angiography study

Obstructive sleep apnoea (OSA) is associated with significantly increased risk of cardiovascular disease. Carotid ultrasonography and retrospective, uncontrolled, coronary imaging studies have suggested an association of OSA with subclinical atherosclerosis, but there is a lack of prospective, controlled studies directly evaluating the relationship of OSA with occult coronary artery disease. We performed coronary computed tomographic angiography and inpatient-attended sleep studies on a cohort of otherwise healthy males attending our sleep laboratory, and compared coronary artery plaque volume between subjects with low and high apnoea/hypopnoea index (AHI) scores. 29 subjects participated. The median AHI was 15.5 events · h(-1), with subjects who scored above this classified as high AHI. No significant differences were observed in demographic, anthropometric and clinical variables between the high- and low-AHI groups. Coronary plaque volume was significantly greater in the high-AHI group (mean plaque volume 2.6 ± 0.7 mm(2) versus 0.8 ± 0.2 mm(2); p=0.017) and, furthermore, correlated significantly with AHI (Spearman's r=0.433; p=0.019). Following adjustment for dyslipidaemia and fasting plasma glucose levels, AHI remained a significant predictor of plaque volume (standardised β=0.424; p=0.027). In this prospective case-control study, we found that severity of OSA may predict occult coronary atherosclerosis in otherwise healthy overweight or obese male subjects.

Is size really all that matters? Remarks on size and necrotic core content of atherosclerotic plaques

Is size really all that matters? Remarks on size and necrotic core content of atherosclerotic plaques

Fully automatic three‐dimensional quantitative analysis of intracoronary optical coherence tomography

Quantitative analysis of intracoronary optical coherence tomography (OCT) image data (QOCT) is currently performed by a time-consuming manual contour tracing process in individual OCT images acquired during a pullback procedure (frame-based method). To get an efficient quantitative analysis process, we developed a fully automatic three-dimensional (3D) lumen contour detection method and evaluated the results against those derived by expert human observers. The method was developed using Matlab (The Mathworks, Natick, MA). It incorporates a graphical user interface for contour display and, in the selected cases where this might be necessary, editing. OCT image data of 20 randomly selected patients, acquired with a commercially available system (Lightlab imaging, Westford, MA), were pulled from our OCT database for validation. A total of 4,137 OCT images were analyzed. There was no statistically significant difference in mean lumen areas between the two methods (5.03 + or - 2.16 vs. 5.02 + or - 2.21 mm(2); P = 0.6, human vs. automated). Regression analysis showed a good correlation with an r value of 0.99. The method requires an average 2-5 sec calculation time per OCT image. In 3% of the detected contours an observer correction was necessary. Fully automatic lumen contour detection in OCT images is feasible with only a select few contours showing an artifact (3%) that can be easily corrected. This QOCT method may be a valuable tool for future coronary imaging studies incorporating OCT.

Unusual case of paradoxical multisite embolization in a patient with patent foramen ovale

A 77 years old white woman was admitted to our coronary care unit for evaluation and treatment of acute myocardial infarction, associated with right arm hypostenia, two hours from the onset of chest pain. The standard ECG showed sinusal rhythm with ST segment elavation in the antero-lateral and inferior leads. The emodynamic parameters remained stable. Neurological evaluation confirmed the diagnosis of ischemic stroke in the distribution area of the left middle cerebral artery. The only cardiovascular risk factor was hypertension. The patient was immediately moved to the cardiac catheterization laboratory for angiographic evaluation and possible primary percutaneous transluminal coronary angioplasty. Coronary imaging studies showed evidence of complete thrombotic occlusion of the left anterior descending artery (LAD) in its distal tract (Fig. 1), that was no treated with angioplasty because of its small diameter. The other coronary arteries appeared normal. The creatine–kinase MB fraction peak was 69 ng/ml in the ninth hour. A trans-thoracic echocardiogram showed normal ejection fraction, with septal hypertrophy (15–16 mm). Cerebral computed tomography performed two days later showed signs of chronic ischemic damage, probably due to a multiple micro-embolisms. A diagnostic investigation to evaluate a possible hypercoagulability syndrome was carried out measuring antithrombin II, protein C and S, prothrombin time, partial thromboplastin time, fibrinogen and homocysteine concentrations, cardiolipin antibodies, and genotype analysis for factor II and factor V Leiden. All the laboratory findings were within normal limits. Evaluation of the carotid arteries, with colordoppler ultrasounds, did not show any evidence of significant atheromatous change or obstruction. A trans-oesophageal echocardiogram, performed to identify a possible cardiogenic source of thrombotic embolization,