Cardiac Imaging for Risk Stratification in Diabetes JEROEN J. BAX, MD 1 SILVIO E. INZUCCHI, MD 2 ROBERT O. BONOW, MD 3 JOANNE D. SCHUIJF, MSC 1 MICHAEL R. FREEMAN, MD 4 EUGENE J. BARRETT, MD 5 ON BEHALF OF THE GLOBAL DIALOGUE GROUP FOR THE EVALUATION OF CARDIOVASCULAR RISK IN PATIENTS WITH DIABETES W orldwide, 200 million individu- als currently have diabetes, and projections by the World Health Organization and others suggest that its prevalence will exceed 300 million by 2025 and 360 million by 2030 (1,2). More than 90% of these individuals will have type 2 diabetes. Management guide- lines in Europe (3) and the U.S. (4) consider type 2 diabetes to be a cardiovas- cular disease equivalent. These patients have a two- to fourfold higher risk of a cardiovascular event than nondiabetic pa- tients. Importantly, cardiovascular death is the most common cause of mortality in the type 2 diabetic population (5). It has been estimated that after a myocardial in- farction, 79% of diabetic patients die of cardiac complications (6). Accordingly, accurate cardiovascular risk stratification of patients with type 2 diabetes is needed. This can be problematic in that the clini- cal presentation and progression of coro- nary artery disease (CAD) differs between diabetic and nondiabetic patients. In ad- dition to a higher prevalence of CAD (7), patients with diabetes experience more diffuse, calcified, and extensive CAD, more often have left ventricular dysfunc- tion, often have more advanced coronary disease at the time of diagnosis, and more often experience silent ischemia. In addi- tion, diabetic patients generally have a less favorable response to revasculariza- tion (with frequent need for repeat percu- taneous coronary intervention or coronary artery bypass grafting) and a reduced long-term survival. Accordingly, early accurate diagnosis of CAD in patients with diabetes is needed, and reliable prognostication is mandatory. The American Diabetes Asso- ciation has recommended an algorithm whereby symptomatic diabetic patients would be referred for either stress perfu- sion imaging or stress echo or evaluation by a cardiologist. The exception would be individuals with atypical chest pain and a normal electrocardiogram who might un- dergo a simple exercise stress test unless they have multiple other cardiovascular risk factors, in which case imaging studies would be preferred (8). The purpose of the present review is to discuss the available imaging tech- niques in assessing CAD in symptomatic patients with diabetes (and compare ob- servations to the accuracy of the techniques in the general population). In addition, the issue of screening CAD in asymptom- atic diabetic patients is discussed. HOW IS CAD DIAGNOSED? The “gold standard” for detection of CAD remains invasive angiography with ves- sel-selective contrast injection of the cor- onary arteries. Both spatial (0.2 mm) and temporal (5 ms) resolution of the tech- nique are extremely high, and the degree of luminal narrowing can be quantified precisely. This is an invasive and expen- sive procedure with a small but definite risk for complications. Noninvasive test- ing is increasingly used to assess CAD, and multiple methods are now unavail- able. These can be divided into functional imaging, which detects the hemodynamic consequences of CAD (i.e., ischemia), and anatomical imaging, which detects atherosclerosis and permits direct visual- ization of the coronary arteries. Functional imaging The basis of functional imaging is the de- tection of CAD by assessing the hemody- namic consequences (i.e., ischemia) of CAD rather than direct visualization of the coronary arteries. A sequence of events occurs during induction of isch- emia, referred to as “the ischemic cascade” (9). Early (within seconds) in the isch- emic cascade, perfusion abnormalities occur, and systolic wall motion abnor- malities follow within 10 –20 s. Electro- cardiogram (ECG) changes and angina occur only at the end of the cascade. Ac- cordingly, exercise ECG is predictably not the most sensitive technique, and its di- agnostic accuracy has been demonstrated to be low in patients with diabetes (10). Conversely, abnormalities in perfusion and systolic wall motion are early markers of ischemia. While perfusion abnormali- ties should be the more sensitive of the two for assessment of ischemia, in daily practice both phenomena are similarly sensitive. A number of imaging techniques can assess myocardial perfusion, including nuclear techniques (i.e., positron emis- sion tomography [PET] or single photon emission computed tomography [SPECT]), first-pass perfusion imaging with magnetic resonance imaging (MRI), and myocardial contrast echocardiogra- phy. For assessment of systolic wall mo- tion, the following techniques are used: two-dimensional stress echocardiogra- ●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●● From the 1 Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands; 2 Section of Endocrinology, Department of Medicine, Yale University School of Medicine, New Haven, Connecticut; 3 Division of Cardiology, Northwestern University Feinberg School of Medicine, Chicago, Illinois; the 4 Di- vision of Cardiology, University of Toronto, Toronto, Ontario, Canada; and the 5 Department of Internal Medicine, University of Virginia, Charlottesville, Virginia. Address correspondence and reprint requests to Jeroen J. Bax, MD, PhD, Department of Cardiology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, Netherlands. E-mail: j.j.bax@lumc.nl. Received for publication 11 October 2006 and accepted in revised form 18 January 2007. Published ahead of print at http://care.diabetesjournals.org on 26 January 2007. DOI: 10.2337/dc06- 2094. J.J.B. has received research grants from GE Healthcare and BMS Medical, and R.O.B. is a consultant for Bristol-Meyers Squibb Medical Imaging. Additional information for this article can be found in an online appendix available at http://dx.doi.org/ 10.2337/dc06-2094. Abbreviations: CAD, coronary artery disease; EBCT, electron beam computed tomography; DIAD, De- tection of Silent Myocardial Ischemia in Asymptomatic Diabetics; ECG, electrocardiogram; MRI, magnetic resonance imaging; MSCT, multislice computed tomography; PET, positron emission tomography; SPECT, single photon emission computed tomography. A table elsewhere in this issue shows conventional and Syste `me International (SI) units and conversion factors for many substances. © 2007 by the American Diabetes Association. Reviews/Commentaries/ADA Statements R E V I E W A R T I C L E DIABETES CARE, VOLUME 30, NUMBER 5, MAY 2007 1295