Over the course of the last three decades, large clinical trials have established that targeting major cardiovascular risk factors has a profound effect on clinical event rates Citation[1]. However, despite increasing emphasis on these approaches in treatment guidelines for cardiovascular prevention, there remains a considerable residual clinical risk Citation[2]. This supports the need to develop more effective strategies to determine the cardiovascular risk of individual patients and therapeutic interventions to result in more effective prevention of cardiovascular disease.
Considerable interest has focused on the use of arterial wall imaging in clinical practice and the development of new anti-atherosclerotic agents. This is based on the premise that most cardiovascular events result from the buildup of atherosclerotic plaque within the artery wall and on autopsy reports of the association between plaque burden and sudden cardiac death Citation[3]. Coronary angiography is widely used to diagnose and quantify the extent of obstructive disease. This enables triage of patients with a range of medical and revascularization strategies. In addition, quantitative coronary angiography has been used in a serial fashion to evaluate the effect of medical therapies on disease progression Citation[4,5].
While angiography is of critical importance in clinical practice, there are a number of issues that limit further expansion of its use. Coronary angiography generates a 2D silhouette of the arterial lumen. Given that it does not image the artery wall, it does not directly visualize atherosclerotic plaque. Advances in intravascular imaging enable visualization of the full atherosclerotic plaque burden within the artery wall, in terms of its volumetric extent and tissue composition. While these diseases feature association with adverse cardiovascular outcomes Citation[6,7], their optimal use in clinical practice remains uncertain.
The requirement for invasive coronary catheterization prevents its use in the diagnosis of subclinical atherosclerosis and risk stratification in asymptomatic individuals. Accordingly, there has been a proliferation of interest in the development of noninvasive techniques that can image the artery wall. Measurement of carotid intima–medial thickness and coronary calcium have both been demonstrated to associate with cardiovascular risk Citation[8,9]. Computed tomographic imaging of the coronary arteries has also been feasible, with evidence of a high negative predictive value for clinical events in patients deemed to be at intermediate risk by conventional risk factor algorithms Citation[10]. However, to date, no clinical trial has been performed to determine whether such noninvasive imaging changes the management and ultimately the clinical outcome of patients in the preventive cardiology setting.
An additional use of these approaches has been in the early clinical development of novel anti-atherosclerotic therapies. While angiography has been used in early clinical trials of medical therapies, its inability to directly visualize atherosclerotic plaque limits its application in this area. Intravascular imaging has demonstrated the ability of agents to slow disease progression Citation[11], promote plaque regression Citation[12] and, in some instances, favorably modify plaque composition Citation[13]. However, the requirement for an invasive procedure limits the number of times this can be performed in a given patient. While noninvasive imaging has also been used in this setting Citation[10], this has largely been confined to the larger vessels and excludes imaging of coronary atherosclerosis, the ultimate cause of most cardiovascular events. As a result of these limitations, there is an ongoing need to develop a reliable and accurate noninvasive tool for coronary imaging.
For more than a decade, magnetic resonance has held considerable promise with regard to its potential to image the heart and vasculature. High-resolution imaging of cardiac structure and function has resulted in increasing integration of magnetic resonance in clinical practice. In parallel, considerable efforts have been undertaken to develop magnetic resonance to image atherosclerotic plaque. When performed in the aorta and carotid arteries, magnetic resonance has been performed to demonstrate both burden and composition of atherosclerotic plaque with high resolution Citation[14]. The potential also exists to combine magnetic resonance with molecular targeted contrast agents to further examine plaque functionality Citation[15]. This has been increasingly used in clinical trials that have been reported to demonstrate potentially favorable effects of established therapies Citation[16] and lack the adverse effects of novel agents Citation[17]. However, these studies have been relatively small, limited to a few specialized centers and lack standardization in terms of their image acquisition, analysis and reporting of end points.
Image resolution with magnetic resonance has currently prevented adequate coronary imaging in most centers. As a result, magnetic resonance cannot currently be used for either clinical detection of atherosclerosis or drug evaluation in the coronary vessels. While advances in imaging technology have improved image resolution, it remains to be determined whether this will ultimately enable coronary visualization. Without such developments, the once-hyped speculation that magnetic resonance will become the ‘one-stop shop’ for cardiovascular imaging will remain unfulfilled.
Financial & competing interests disclosure
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
No writing assistance was utilized in the production of this manuscript.
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