Does the Use of Nitroglycerin at MR Angiography Help Diagnose Coronary Artery Disease?

See article by Zhao et al in this issue.

Christopher J. François, MD, is a professor of radiology in the cardiovascular and thoracic imaging sections at the University of Wisconsin School of Medicine and Public Health, as well as chief of the cardiovascular imaging section and director of the MRI Fellowship. His main area of clinical expertise includes cardiovascular MRI and CT and thoracic imaging. His research interests focus on developing and validating new noninvasive cardiac MRI and CT methods for improving our understanding of cardiovascular diseases, including ischemic heart disease, congenital heart disease, pulmonary hypertension, and aortic dissection.

Cardiovascular diseases, including coronary artery disease (CAD), are the number one cause of death worldwide. Many of the deaths from CAD occur in patients younger than 70 years of age. The risk factors for developing CAD are known and include hypertension, hyperlipidemia, diabetes mellitus, history of smoking, and obesity. However, identifying patients with CAD and determining which patients with CAD are at highest risk of myocardial infarction remains a diagnostic challenge. The initial evaluation of patients suspected of having CAD, based on clinical symptoms, typically includes (a) stress testing, without or with imaging, to assess for myocardial ischemia or (b) noninvasive coronary artery angiographic imaging to assess for coronary artery stenosis (1). Exercise or pharmacologic stress testing is usually performed clinically in conjunction with echocardiography, SPECT, or cardiac MRI. Although early noninvasive coronary angiography with the use of MR angiography was promising (2), noninvasive coronary artery imaging is now usually conducted clinically with coronary CT angiography because of its high spatial resolution and very rapid acquisition time. Potential benefits of using coronary MR angiography rather than coronary CT angiography are the ability to perform a complete cardiac morphology and functional evaluation, including stress testing, without the need for ionizing radiation or nephrotoxic contrast material.

In this issue of Radiology: Cardiothoracic Imaging, Zhao et al (3) report the results of a coronary MR angiography study in patients undergoing x-ray coronary angiography in which the investigators determined the effects of applying sublingual nitroglycerin with the performance of coronary MR angiography. This is a follow-up to a study this group performed in healthy volunteers in which coronary artery diameters increased approximately 25% with the administration of sublingual nitroglycerin (4). In the current study, coronary MR angiography was performed before and after the administration of 0.4 mg of sublingual nitroglycerin with a clinically standard, whole-heart, three-dimensional steady-state free precession sequence. Coronary angiography was performed after the coronary MR angiography and was used as the standard of reference for coronary MR angiography. Because heart rate was higher after sublingual nitroglycerin administration, coronary MR angiography scan times were significantly shorter by approximately 0.75 minute after administration of nitroglycerin. The coronary MR angiography image quality significantly improved, and the number of coronary artery segments that could be evaluated (≥ 2 mm diameter) increased after nitroglycerin administration. This led to a change in diagnosis in eight patients, 37 vessels, and 116 segments.

With regard to diagnostic accuracy, nitroglycerin significantly improved per-segment specificity (from 80% to 94%), positive predictive value (from 43% to 70%), and accuracy (from 82% to 94%), while maintaining very high sensitivity (99%) and negative predictive value (100%) (3). The improvement in diagnostic accuracy of coronary MR angiography with sublingual nitroglycerin is expected, given the literature supporting its beneficial effects at coronary CT angiography (5). Given the evidence supporting its use in coronary CT angiography and prior coronary MR angiographic studies reporting its use (2), it is surprising that nitroglycerin is still not routinely used prior to coronary MR angiography.

Another interesting observation in this study was that in patients with stenosis of 50% or more at coronary angiography, the amount of change in coronary artery diameter with coronary MR angiography was significantly less than in patients with stenosis of 50% or less (3). In patients with 50% or more stenosis, the coronary arteries dilated approximately 15%–16% after nitroglycerin administration compared with 22%–28% in patients with 50% stenosis or less. The degree of vasodilation reported in this study is on the same order as that reported previously with coronary CT angiography (5) and cardiac MRI (6). The lower degree of vasodilation in patients with moderate and severe coronary artery stenosis is also concordant with our current understanding of the effects of atherosclerosis on vascular reactivity (2,7). In fact, studies performed by Nguyen et al (6) and Terashima et al (8) reported impaired coronary vasodilation with coronary MR angiography in patients with severe CAD. Although decreased vasoreactivity was not investigated prospectively as a diagnostic criterion for coronary artery stenosis, this is a criterion that should be used in future research.

Sublingual nitroglycerin is a relatively fast-acting vasodilator with effect onset in approximately 1 to 3 minutes, peak onset at approximately 5 minutes, and half-life of approximately 2 to 3 minutes. With these time constraints, there are few issues with performing coronary CT angiography during the window of maximum dilation. Coronary MR angiography, on the other hand, takes much longer to acquire with the same coverage and spatial resolution as that of coronary CT angiography. In this study by Zhao et al, the mean coronary MR angiography acquisition time was approximately 10 minutes (3). An alternative to sublingual nitroglycerin would be to use a longer-acting nitrate, such as isosorbide dinitrate, which Kim et al (2) and Hu et al (9) have reported on previously.

In summary, coronary MR angiography has been looked at with great promise for more than 20 years since the earliest studies on its use in the mid to late 1990s. In this study, Zhao et al (3) report on the improved diagnostic accuracy of coronary MR angiography when performed after nitroglycerin administration, and present data on how the degree of vasodilation could potentially provide complementary information on the effects of atherosclerosis on coronary vascular function in patients with CAD. With the recently presented results of the ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) trial (10) indicating that patients with stable CAD can be treated effectively with lifestyle modifications and medical management, rather than revascularization, there will be a greater focus on the use of noninvasive diagnostic tools for detecting CAD. Although coronary CT angiography is certainly feasible, coronary MR angiography (potentially combined with a comprehensive cardiac MRI) presents an attractive alternative that avoids the use of ionizing radiation and nephrotoxic contrast material.