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J Am Coll Cardiol Img, 2009; 2:774-786, doi:10.1016/j.jcmg.2009.01.017
© 2009 by the American College of Cardiology Foundation
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The Year in Imaging

The Year in Coronary Artery Disease

Stephan Achenbach, MD*,*, Vasken Dilsizian, MD{dagger}, Christopher M. Kramer, MD{ddagger}, William A. Zoghbi, MD§

* Department of Cardiology, University of Erlangen, Erlangen, Germany
{dagger} Departments of Radiology and Medicine, University of Maryland School of Medicine, Baltimore, Maryland
{ddagger} Departments of Medicine and Radiology, University of Virginia Health System, Charlottesville, Virginia
§ Department of Cardiology, The Methodist DeBakey Heart and Vascular Center, Houston, Texas


   Abstract
Top
 Abstract
New Technology
 Diagnosis of CAD
 Imaging of Viability
 Prognosis/Risk Stratification
 New Guidelines and Statements
 REFERENCES
 
Technology in cardiovascular imaging continues to evolve rapidly. Along with new technology, new imaging approaches are continuously being developed and evaluated in various clinical settings. The workup of patients with coronary artery disease (CAD) is one of the major areas in which imaging is applied. Some of the most important aspects include diagnosing CAD through direct coronary visualization or imaging of ischemia; assessing left ventricular function, scar, and viability; and providing prognostic information both in patients with known CAD and in asymptomatic individuals at risk for disease. This article will outline some of the recent developments in the field of echocardiography, nuclear imaging, cardiac magnetic resonance (CMR), and computed tomography (CT) as they pertain to CAD.

Key Words: cardiac magnetic resonance • CAD • computed tomography • echocardiography • speckle tracking imaging


   New Technology
Top
 Abstract
 New Technology
Diagnosis of CAD
 Imaging of Viability
 Prognosis/Risk Stratification
 New Guidelines and Statements
 REFERENCES
 
Improvements in imaging technology comprise advances in hardware that result in better performance and new pharmacological agents, as well as new software approaches to image processing and analysis. In echocardiography, automated methods for quantitation of regional function with speckle tracking of reflected ultrasound waves and velocity vector imaging, a feature tracking technique, were validated in animal models (1,2). Myocardial strain and strain rate derived with these methods correlated well with independent standards of regional function during ischemia-reperfusion or with dobutamine stimulation with increasing degrees of coronary stenosis (1,2). These methods allow quantitative and objective interpretation of regional function that can be used for detection of CAD in rest and stress studies or to assess the burden of ischemia during acute coronary syndromes.

New hardware was seen in nuclear imaging. A high-speed, myocardial perfusion single-photon emission computed tomography (SPECT) camera has been introduced (Fig. 1) (3). It uses a bank of independently controlled detector columns with large-hole tungsten collimators and multiple cadmium zinc telluride crystal arrays. In 44 patients undergoing Tc-99m sestamibi myocardial perfusion imaging, stress and rest acquisition times were 16 and 11 min for conventional SPECT but only 4 and 2 min for high-speed SPECT, respectively. With high-speed SPECT, myocardial count rates were 7- to 8-fold higher than in conventional SPECT, with 97% of images graded as "good" or better. Moreover, the level of diagnostic confidence was equal for both SPECT systems, and myocardial perfusion uptake scores correlated closely (r = 0.93) (3). If these initial results are confirmed in a larger patient population using quantitative analysis, high-speed SPECT systems might pave the way for new radiotracers and pharmacologic stressors in the future.


Figure 1
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  		Figure 1 Myocardial Perfusion Imaging by Conventional and High-Speed SPECT in a Patient With Previous Myocardial Infarction

Conventional single-photon emission computed tomography (SPECT) (top) and high-speed SPECT (bottom) images showing infarct and ischemia of the left anterior descending coronary artery and ischemia of the right coronary artery. High-speed SPECT images are characterized by better resolution with clearer edge definition and thinner ventricular walls. The inferior ischemia is better seen with high-speed SPECT images. Reproduced with permission from Sharir et al. (3).

 
In addition, a new A2A-selective adenosine receptor agonist, regadenoson, was introduced for pharmacologic myocardial perfusion stress testing with SPECT (4). The commonly used pharmacologic vasodilators adenosine and dipyridamole stimulate all 4 adenosine receptor subtypes. Stimulation of the A2A receptor subtype causes the differential coronary arterial dilation required for myocardial perfusion SPECT imaging. Regadenoson induces a 2- to 3-fold increase in myocardial blood flow for 3 to 4 min. In 2,015 patients from Phase 3 trials, noninferiority of regadenoson for the detection of myocardial ischemia was demonstrated as compared with adenosine (4). Regadenoson caused more headache and gastrointestinal discomfort but had a lower combined symptom score and caused less chest pain, flushing, and throat/neck/jaw pain.

CT technology continues to undergo rapid technological evolution. Despite tremendous progress made in the past years, spatial and especially temporal resolution continue to pose a challenge when coronary artery visualization is attempted. After dual source CT was introduced in 2006 with a high diagnostic accuracy for coronary stenosis detection, preserved at high heart rates (5,6), 2 manufacturers introduced CT systems that have substantially wider detectors and allow simultaneous sampling of 256 or even 320 slices (7). Therefore, it is theoretically possible to acquire all necessary data in a single rotation of the gantry, in 1 single cardiac cycle, thus avoiding misregistration or misalignment artifacts that can occur with more narrow detectors. For higher heart rates, data sampling might extend over 2 or 3 consecutive heartbeats to allow for multi-segment reconstruction (7).

Another area of intense interest was the radiation exposure associated with CT imaging in general and cardiac CT imaging in particular (8,9) and newer approaches to lower the radiation exposure during coronary computed tomography angiography (CTA). One possible advance is the reduction of tube current to 100 kV (as opposed to the standard 120 kV), which can lower radiation exposure by 30% to 40% while maintaining diagnostic accuracy in nonobese patients (10). Another even more effective approach is to change the acquisition mode from retrospectively gated "spiral" or "helical" acquisition to "prospectively triggered" or "step-and-shoot" protocols. Several studies have reported very low effective radiation doses for such protocols, ranging from 1.2 to 4.3 mSv and a reduction of radiation exposure by 77% to 83% compared with conventional protocols (Fig. 2) (11–17). Prospective triggering seems to be a valuable alternative to conventional spiral image acquisition approach for coronary CTA, especially in patients with a low heart rate (below 60 to 65 beats/min) (18).


Figure 2
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  		Figure 2 Coronary Computed Tomography Angiography With Low Radiation Exposure

Curved multiplanar reconstructions of the right coronary artery (A), left anterior descending coronary artery (B), and left circumflex coronary artery (C) obtained by contrast-enhanced dual source computed tomography. Imaging was performed with prospective triggering (thus, X-rays were emitted only during 1 pre-specified time instant in diastole) and with a tube voltage of 100 kVp (instead of the more frequently used 120 kVp). Estimated effective radiation dose for this scan was 1.8 mSv.

 
New scanning sequences were introduced for 3-T cardiac magnetic resonance (CMR) imaging. A new sequence for myocardial perfusion imaging with highly parallel imaging in a 3-T magnet, which was validated in 14 volunteers and 37 patients, allowed for high spatial resolution and showed similar diagnostic accuracy for detection of CAD but with improved image quality and reduced artefacts compared with 1.5-T (19).


   Diagnosis of CAD
Top
 Abstract
 New Technology
 Diagnosis of CAD
Imaging of Viability
 Prognosis/Risk Stratification
 New Guidelines and Statements
 REFERENCES
 
One of the major goals of imaging in the context of CAD is the identification of patients, vessels, and stenosed coronary segments that lead to ischemia. Basically, 2 approaches are possible: direct visualization of the coronary arteries (e.g., by cardiac CT) or demonstration of downstream effects caused by coronary stenoses, such as wall motion abnormalities or impaired myocardial perfusion (by echocardiography, nuclear imaging, and CMR). In echocardiography, advances have been made both for wall motion and perfusion analysis. The OPTIMZE (A Randomized Cross-Over Study for Evaluation of the Effect of Image Optimization With Contrast on the Diagnostic Accuracy of Dobutamine Echocardiography in Coronary Artery Disease) trial evaluated endocardial border image optimization with contrast on the diagnostic accuracy of dobutamine stress echocardiography (DSE) in the detection of CAD (20). In 101 patients who underwent 2 DSE studies, 1 without and 1 with contrast enhancement with perflutren lipid microspheres (Definity, Bristol-Myers Squibb, Billerica, Massachusetts), contrast improved the percent of segments adequately visualized at baseline (from 72 ± 24% to 95 ± 8%) and even more so at peak stress (67 ± 28% to 96 ± 7%). Interpretation of wall motion with high confidence also increased from 36% to 74% with the use of contrast. As the extent of endocardial visualization and confidence of interpretation decreased in nonenhanced studies, an increased impact of contrast on DSE accuracy compared with angiography was observed.

In addition to wall motion analysis, the assessment of myocardial perfusion using echo contrast agents further enhances the detection of patients with CAD compared with assessment of wall motion alone. In a study involving 50 patients, real-time myocardial perfusion with contrast was performed during DSE. Subendocardial perfusion abnormalities that corresponded to myocardial ischemia were observed in areas where wall thickening was still preserved (21) and could further enhance the accuracy of DSE for the detection of CAD (Fig. 3).


Figure 3
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  		Figure 3 Echocardiographic Measurement of Subendocardial Wall Thickening With Myocardial Contrast

Apical 4-chamber view of real-time myocardial contrast echocardiography with contrast pulse sequencing was obtained from a patient with significant left anterior descending coronary artery disease during dobutamine stress. Note the perfusion defect. The end-diastolic (ED) and end-systolic (ES) wall thickness (WT) for transmural wall thickening are measured on the pre-myocardial contrast replenishment (MCR) images (the first cardiac cycle after the high mechanical index impulse) (left panels) as the distance between the endocardial border (blue arrows) delineated with left ventricular cavity contrast and the epicardial border (blue arrows). Subendocardial wall thickening was measurable only if a subendocardial perfusion defect was present (red arrows) during the replenishment period (MCR) (right panels). Reproduced with permission from Xie et al. (21).

 
In October 2007, the U.S. Food and Drug Administration issued a Boxed Warning regarding the safety of echo contrast agents, particularly in hemodynamically unstable patients. Since then, several safety studies published in 2008, including a multicenter retrospective study sponsored by the American Society of Echocardiography, have become available (22–25) and helped reverse the newly stated contraindications in May 2008. Thus, heart failure, acute coronary syndromes, arrhythmias, and pulmonary disease no longer constitute contraindications to the use of microbubble contrast agents; high-risk patients with pulmonary hypertension or unstable cardiopulmonary conditions still need to be monitored for 30 min after administration.

Beyond perfusion, nuclear imaging allows assessment of cardiac metabolism. Increased glucose metabolism is a hallmark of reversibly ischemic myocardium. In 24 patients with strong clinical suspicion of CAD, simultaneous dual-isotope injection of sestamibi and fluorodeoxyglucose (FDG) at peak exercise and rest was performed (26). The metabolic signal with FDG was more sensitive than sestamibi myocardial perfusion SPECT for detecting myocardial ischemia. Among patients with abnormal FDG uptake at peak exercise, 47% exhibited residual abnormal FDG uptake at rest, 24 h after the exercise-induced ischemia, consistent with the concept of "ischemic memory," which provides the potential for diagnosing myocardial ischemia in the acute care setting. Thus, metabolism plays a critical role in sustaining myocellular viability by adapting quickly to the ischemic injury response but with recovery of metabolism lagging behind perfusion for 24 h or more (27).

For the detection of CAD, CT relies almost exclusively on the direct visualization of the coronary arteries. During the past year, several analyses have clearly demonstrated the superiority of 64-slice CT over previous technology (28–34) for the detection of coronary artery stenoses. Several meta-analyses demonstrated high sensitivities (96% to 99%) and (93% to 94%) for CAD in individuals with at least 1 coronary artery stenosis (Table 1). For the detection of in-stent stenoses, 2 additional meta-analyses demonstrated insufficient sensitivity of coronary CTA (82% and 84%) (35,36).


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  		Table 1 Meta-Analyses of the Accuracy of Contrast-Enhanced 64-Slice Coronary Computed Tomography Angiography to Identify Coronary Artery Stenoses
 
Three large multicenter trials concerning the accuracy of 64-slice CT for stenosis detection have been published (37–39) (Table 2). The ACCURACY (Assessment by Coronary Computed Tomographic Angiography of Individuals Undergoing Invasive Coronary Angiography) trial studied 230 patients with suspected CAD (37). Prevalence of disease was 25%, and per-patient sensitivity and specificity for detecting individuals with at least 1 stenosis ≥50% was 95% and 83%, respectively. The negative predictive value was 99%, but the positive predictive value was only 64%. The Core64 (Coronary Artery Evaluation Using 64-Row Multidetector Computed Tomography Angiography) trial studied a group of 291 patients with a different composition. Prevalence of obstructive disease was 56%, and 30% of the patients had previous myocardial infarction (MI) or coronary revascularization (38). Per-patient sensitivity was 85% and specificity was 90% (negative predictive value 83%, and positive predictive value 91%). Finally, Meijboom et al. (39) published a trial performed at 3 different sites, which enrolled 360 patients with stable (n = 233) or unstable symptoms (n = 127). Prevalence of obstructive disease was 68%, and 64-slice CT had a sensitivity of 99% but only 64% specificity for the identification of individuals with at least 1 coronary artery stenosis (Fig. 4). The results of these trials provide further evidence that CTA can be highly reliable to rule out the presence of CAD but that its performance strongly depends on the type of patients evaluated.


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  		Table 2 Multicenter Studies That Addressed the Accuracy of Coronary Artery Stenosis Detection by Contrast-Enhanced 64-Slice Coronary Computed Tomography Angiography
 

Figure 4
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  		Figure 4 CTA With a 64-Slice Scanner in a Patient With Significant Stenoses of the RCA

A thick maximum-intensity projected coronary computed tomography angiography (CTA) image (A) shows the anatomy of the right coronary artery (RCA). A curved multiplanar reformatted image (B) discloses a significant coronary stenosis (arrows) in the mid RCA and a stenosis of intermediate degree further distally (arrowheads). Both lesions were corroborated by conventional coronary angiography (C). Reproduced with permission from Meijboom et al. (39).

 
In a study of 80 patients it was shown that coronary CTA can identify "high-risk" coronary anatomy (40). Several recent studies studied the effect of CTA on downstream testing and demonstrated that a coronary CTA negative for stenoses indicates a very favorable clinical outcome (41–43). Min et al. (44) identified 1,647 individuals in whom coronary CTA was performed without previously known CAD. He showed that the rate of downstream catheterization was substantially lower if CT was performed than in patients in whom stress myocardial perfusion imaging had been performed (1.7% vs. 9.6%). The rate of downstream revascularization was 0.2% versus 0.8%, but outcomes were no worse for CTA as the initial test, with a lower rate of hospital stay for CAD (0.7% vs. 1.1%) and a lower rate of angina (4.3% vs. 6.4%).

Although CMR also has the potential to visualize the coronary arteries, image quality is often impaired, and the analysis of perfusion, wall motion, or infarct scars has higher accuracy when patients are evaluated regarding the presence of CAD. In a study of 54 patients scheduled for invasive coronary angiography and studied with a combined magnetic resonance technique of coronary imaging, first-pass perfusion, and late gadolinium enhancement (LGE), coronary magnetic resonance angiography added little value (sensitivity 91%, specificity 46%), whereas perfusion alone yielded the best results (sensitivity 87%, specificity 88%) (45). In fact, a multicenter study comparing SPECT with contrast-enhanced myocardial perfusion CMR in 234 patients demonstrated better overall diagnostic accuracy for CMR (46). In a study performed at 3-T with vasodilator stress perfusion imaging in 101 patients with high prevalence of CAD (69%), sensitivity was 90%, specificity 71%, and overall accuracy was 84% for the detection of high-grade coronary stenoses (47). Evidence of myocardial ischemia without obstructive epicardial disease was demonstrated in 56% of 18 syndrome X patients with vasodilator stress perfusion CMR. The CMR findings correlated significantly to measures of coronary flow reserve in the left anterior descending coronary artery territory (r = –0.45, p = 0.019) (48).

CMR has the unique potential of visualizing myocardial edema. In 62 individuals presenting to the emergency department with chest pain, a new algorithm incorporating T2-weighted imaging for identification of myocardial edema improved the overall accuracy of standard CMR approaches with first-pass contrast-enhanced perfusion, LGE, and cine-functional imaging from 84% to 93% (49).


   Imaging of Viability
Top
 Abstract
 New Technology
 Diagnosis of CAD
 Imaging of Viability
Prognosis/Risk Stratification
 New Guidelines and Statements
 REFERENCES
 
Imaging of myocardial viability has important implications for making treatment decisions. This has clearly been shown in a noteworthy study of 70 consecutive patients with left ventricular (LV) aneurysm who underwent nuclear imaging by 99mTc-sestamibi SPECT and 18F-FDG positron emission tomography (PET) (50) and were followed for a median period of 6.8 years. Patients were classified into 4 groups by aneurysmal viability and by treatment strategy (medical or surgical). The annual cardiac mortality rate in patients with a viable aneurysm treated medically (n = 10) was significantly higher than that in patients with a viable aneurysm treated surgically (n = 23) (11.6% vs. 1.5%, p < 0.0001) and was also significantly higher than that in patients with a nonviable aneurysm treated medically (n = 14, p < 0.05) or surgically (n = 23, p = 0.001). Multivariate analysis showed that the aneurysmal mismatch score (p = 0.003) and surgical therapy (p = 0.001) were independent predictors of cardiac death. Improvement of LV function and symptoms after revascularization (p < 0.05) was observed in patients with revascularization plus aneurysmectomy and in patients with a viable aneurysm and revascularization only. The findings suggest that the presence of myocardial viability within an LV aneurysm is a negative independent predictor of survival in patients with ischemic cardiomyopathy.

Late enhancement in CMR is frequently used for viability assessment. Gadoversetamide, a new contrast agent, was evaluated for detection of acute and chronic MI in 566 patients who were randomized to doses between 0.1 and 0.3 mmol/kg, and a dose of ≥0.2 mmol/kg was sensitive for scar visualization (51). CMR late enhancement was used in studies to assess pharmacologic reduction of infarct size during reperfusion of acute MI (52). T2-weighted imaging (which can visualize myocardial edema) (Fig. 5) came to the fore as a method to image the salvaged area at risk in a study of 92 patients with reperfused acute MI (53). The area of increased T2-signal was 16% greater than the area of LGE. A comprehensive study of recovery of regional and global function after acute MI demonstrated that the presence of microvascular obstruction was the most powerful predictor, more powerful than the transmural extent of infarction (54). In a different setting, CMR late enhancement imaging was used to show that the incidence of new irreversible myocardial injury/scar was higher in patients with on-pump beating heart coronary artery bypass graft surgery than in on-pump conventional coronary artery bypass graft surgery in 50 patients with reduced LV function (55).


Figure 5
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  		Figure 5 Visualization of Myocardial Edema in T2-Weighted CMR (Short-Axis View)

(Left) T2-weighted cardiac magnetic resonance (CMR) image of a healthy subject with a homogeneous low signal intensity of the myocardium. (Right) T2-weighted CMR image of a patient with an acutely reperfused inferior infarction. The infarct-related injury is visually apparent by a thickened myocardium with high signal (arrows). Apparent extension into the inferior wall of the right ventricle is visible (arrowhead). Reproduced with permission from Friedrich et al. (53).

 
Similar to CMR, CT allows imaging of function, first-pass perfusion, and even late enhancement. In a small series of 21 patients, it was shown that CT imaging—after injection of iodinated contrast agent—allows identification both of delayed hyperenhancement (detectable in 11 of 15 patients as compared with CMR) and of microvascular obstruction, visible through delayed hypoenhancement (56). CT imaging 5 min after contrast injection provided better image quality than imaging 10 min after injection (57). In 69 patients, Henneman et al. (58) used CT to diagnose healed infarcts through LV myocardial hypoenhancement and demonstrated that CT findings closely correlated to rest SPECT (even though there was a systematic bias toward underestimation of infarct size by CT). A trial of 34 patients with recent acute MI and 68 control subjects demonstrated that the combination of a first-pass perfusion deficit and regional wall motion analysis provided for accurate detection of MI by CT (59).

By echocardiography, the predictive value of myocardial strain imaging for improvement in cardiac function after revascularization was evaluated in 53 patients with ischemic LV dysfunction and compared with contrast-enhanced CMR imaging (60) (Fig. 6). Peak systolic radial strain (cutoff of 17%) predicted recovery of function similarly to CMR late enhancement (echocardiography: sensitivity 70%, specificity 85%; CMR: sensitivity 72%, specificity 92%).


Figure 6
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  		Figure 6 Late-Enhancement Cardiac Magnetic Resonance and Echocardiographic Strain Imaging in Transmural Infarction

Contrast-enhanced cardiac magnetic resonance image (left), echocardiographic color-coded short-axis radial strain images at end-systole (middle), and radial strain tracings (right) for 1 cardiac cycle obtained from the same short-axis view in a patient with chronic left ventricular dysfunction and akinesia of the septal wall. Contrast-enhanced cardiac magnetic resonance imaging indicates transmural infarction with more than 50% late gadolinium enhancement. The tracings for the evaluated segments within the circumference demonstrate a low peak negative systolic radial strain of the septal wall. The segment demonstrated no functional recovery after coronary bypass surgery. Reproduced with permission from Becker et al. (60).

 
Another trial assessed the extent of microvascular damage, evaluated with contrast echocardiography, on the prediction of LV remodeling in the setting of acute MI (61). A total of 110 patients with first reperfused ST-segment elevation MI were evaluated. Multivariate analysis showed that only Thrombolysis In Myocardial Infarction flow grade <3 and the extent of contrast defect (endocardial length >25%) were independently associated with adverse LV remodeling (Fig. 7).


Figure 7
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  		Figure 7 Example of Myocardial Contrast Echocardiography for the Assessment of Functional Recovery

(A) Myocardial contrast echocardiography in 4-chamber view in a patient with left ventricular dysfunction on day 1 after reperfused ST-segment elevation myocardial infarction shows a large contrast defect on the lateral wall (between arrows) with normal end-diastolic volume. (B) Two-dimensional echocardiogram of the same patient at 6-month follow-up shows an enlarged left ventricle. Reproduced with permission from Galiuto et al. (61).

 

   Prognosis/Risk Stratification
Top
 Abstract
 New Technology
 Diagnosis of CAD
 Imaging of Viability
 Prognosis/Risk Stratification
New Guidelines and Statements
 REFERENCES
 
Imaging receives increasing attention for prognostic assessment of patients with known or suspected CAD. Various imaging modalities use imaging of LV function, inducible wall motion abnormalities, and perfusion to identify at-risk individuals. Recently, imaging of myocardial scar tissue and even imaging of metabolism have complemented these approaches. In addition, CT imaging offers the possibility to directly visualize coronary atherosclerotic plaque.

Current guidelines do not recommend routine cardiac stress testing in patients with stable CAD unless they report symptoms of angina. Gehi et al. (62) compared the prognosis of angina, inducible ischemia in treadmill stress echocardiography, or both in 937 outpatients with stable CAD. During a mean follow-up of 3.9 years, coronary events occurred in 7% of patients without angina or inducible ischemia, in 10% of angina alone, in 21% of inducible ischemia alone, and in 23% of those with both angina and inducible ischemia (p < 0.001). Although the presence of angina alone was not associated with events, the presence of inducible ischemia without self-reported angina strongly predicted coronary events (hazard ratio: 2.2; p = 0.005).

Imaging of impaired myocardial fatty acid metabolism by nuclear imaging through beta-Methyl-p- (123I) iodophenyl pentadecanoic acid (BMIPP) SPECT enabled identification of individuals at high risk for CAD death among 318 dialysis patients without prior MI (63) (Fig. 8). Fifty patients (16%) died of cardiac events during a follow-up of 3.6 ± 1.0 years. Cardiac death was significantly associated with highly abnormal BMIPP uptake (summed score of 12 or more; hazard ratio: 21.9) and age of 70 years or older (hazard ratio: 2.4). When BMIPP uptake (metabolism) was assessed in relation to regional thallium uptake (perfusion), the sensitivity and specificity of metabolism/perfusion mismatch for predicting cardiac death were 86% and 88%, respectively. Event-free survival at 3 years was 55% among patients with a BMIPP/thallium mismatch score of 7 or more and 96% in patients with a BMIPP/thallium mismatch score of below 7. These findings support the assertion that altered cardiac metabolism (indicating silent myocardial ischemia) can identify patients who are at high risk for cardiac death. The shift from a predominance of aerobic (fatty acid) to anaerobic (glucose) metabolism seems to account for a significant portion of the excessive cardiovascular morbidity and mortality observed across all stages of kidney disease (64).


Figure 8
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  		Figure 8 Imaging of Myocardial Perfusion and Myocardial Fatty Acids in Dialysis Patients Who Died of Cardiac Events

(A) A 75-year-old woman died of acute myocardial infarction 11 months after single-photon emission computed tomography (SPECT). Coronary angiography within 60 days of beta-methyl iodophenyl-pentadecanoic acid (BMIPP) SPECT revealed significant stenoses in the left main trunk, right coronary artery, left anterior descending artery, and left circumflex artery. The patient refused invasive therapy. (B) A 74-year-old man died of congestive heart failure 31 months after SPECT. Coronary angiography did not find significant stenosis of >50% within 60 days of SPECT. (C) A 61-year-old man died of sudden cardiac events 38 months after SPECT. Coronary angiography did not find significant stenosis within 60 days of SPECT. Reproduced with permission from Nishimura et al. (63). TI = thallium.

 
Although the extent and severity of stress-induced myocardial ischemia have been well-recognized as strong predictors of future CAD events (nonfatal MI or death related to MI, heart failure, or sudden cardiac death), the prognostic relevance of resting myocardial perfusion defects in relation to stress-induced myocardial ischemia has been incompletely described. Among 7,849 consecutive outpatients, time to CAD event (n = 545) was analyzed (65). Among patients without resting myocardial perfusion defects, overall CAD event rates were 1.2%, 8%, and 10% for patients with 0% ischemic myocardium, 1% to 4.9% ischemic myocardium, and 5% ischemic myocardium or greater, respectively (p < 0.0001). As the percent myocardium with resting myocardial perfusion defects worsened, overall CAD event rates increased, such that for patients with 10% or more of the rest myocardium with perfusion defects, cardiovascular death or MI rates ranged from 7% to 44% (p < 0.0001). For every 1% increase in ischemic myocardium, there was a 7% increased risk of CAD events (p < 0.0001). A 3% increase in risk of CAD events was observed for patients with every 1% of the myocardium with resting defects (p < 0.0001).

CMR also allows imaging of both ischemia (perfusion) and scar. In a study of 218 patients with suspected CAD, a normal adenosine stress CMR with an absence of LGE predicted a 99% survival free of major adverse cardiac events over 12 months, suggesting the excellent negative predictive value of this diagnostic test (66). Infarct size as assessed by magnetic resonance late enhancement was shown to be the most powerful predictor of adverse outcomes in a study of 122 patients after ST-segment elevation MI (67). In a trial of 187 diabetic individuals, 109 of whom had no known prior MI, the presence of late enhancement predicted a >4-fold incidence of major adverse cardiac events compared with those without LGE (68).

CT relies on direct visualization of plaque for risk assessment. Some data have become available as to the prognostic implications of plaque seen in coronary CTA. Min et al. (69) demonstrated in 1,127 symptomatic patients studied by contrast-enhanced 16-slice CT that the presence of plaque in more than 5 coronary segments was associated with a significantly increased mortality rate over a mean follow-up period of 15 months. Shaw et al. (70) demonstrated that the prognostic information obtained by CTA is similar to that of SPECT myocardial perfusion imaging. Another group provided long-term (up to 12 years) follow-up data of 2,538 patients studied by contrast-enhanced electron beam tomography. They demonstrated that the presence of obstructive plaque in 1 or more vessels and of nonobstructive plaque in 3 coronary vessels was associated with a significantly increased mortality (whereas the presence of nonobstructive plaque in only 1 or 2 vessels was not) (71). A group from Korea followed 1,000 asymptomatic male, middle-aged individuals for over 17 months and, because plaque and stenoses were not associated with remote coronary events, concluded that their study failed to demonstrate a prognostic benefit of coronary CTA for "screening" purposes (72).

Results of the MESA (Multi-Ethnic Study of Atherosclerosis) trial, published in March 2008, confirmed the prognostic value of coronary artery calcium (CAC) in asymptomatic individuals: in a population-based sample of 6,722 individuals, adding calcium score to standard risk factors significantly increased the area under the receiver-operator characteristic curve for prediction of coronary events (0.77 for risk factors alone vs. 0.82 for risk factors plus coronary calcium, p < 0.0001) (73). In another analysis of the same population, each 1-SD increase of the coronary calcium score was associated with a 2.1-fold hazard ratio for coronary events, whereas each 1-SD increase in intima media thickness was associated with an only 1.3-fold hazard ratio (74).

The incremental prognostic value of CAC over myocardial perfusion was assessed in 695 consecutive patients with intermediate-risk for CAD who underwent rest-stress rubidium 82 PET on a hybrid PET-CT scanner (75). Risk-adjusted survival analysis demonstrated a stepwise increase in event rates (death and MI) with increasing CAC scores in patients with and without ischemia on PET myocardial perfusion imaging. Among patients with normal PET myocardial perfusion imaging, the annualized event rate in patients with no CAC was lower than in those with a CAC score ≥1,000 (2.6% and 12.3%, respectively). Likewise, in patients with ischemia on PET myocardial perfusion imaging, the annualized event rate in those with no CAC was lower than among patients with a CAC score ≥1,000 (8.2% and 22.1%, respectively). These findings suggest that, independent of the presence of ischemia in PET myocardial perfusion imaging, increasing coronary calcium scores are associated with a stepwise increase of the risk of future adverse events.


   New Guidelines and Statements
Top
 Abstract
 New Technology
 Diagnosis of CAD
 Imaging of Viability
 Prognosis/Risk Stratification
 New Guidelines and Statements
REFERENCES
 
Several new statements, guidelines, and recommendations that address issues relevant to the noninvasive imaging of CAD have been published.

The ACCF/ASE/ACEP/AHA/ASNC/SCAI/SCCT/SCMR 2008 appropriateness criteria for stress echocardiography provide a detailed list of indications for stress echocardiography in various clinical situations (76). A consensus statement of the American Society of Echocardiography on the clinical applications of ultrasonic contrast agents details the appropriate clinical use of these agents (77). For CMR, protocols for performing CMR were published to aid in standardizing image acquisition across vendors and institutions (78). A Scientific Statement of the American Heart Association on noninvasive coronary artery imaging summarizes available data and discusses potential indications of coronary artery visualization by magnetic resonance and CT (79). A report of the American College of Cardiology Foundation/American Heart Association and American College of Physicians Task Force on Clinical Competence and Training, endorsed by numerous professional societies, outlines suggested training requirements for multi-modality, noninvasive cardiovascular imaging (80). Finally, 2 statements provide a framework and key data elements for reporting of cardiovascular imaging studies (81,82).


   Footnotes
 
Section Editor: Jeroen J. Bax, MD, PhD

Dr. Achenbach is partly supported by Grant BMBF 01 EV 0708, from Bundesministerium für Bildung und Forschung (BMBF), Bonn, Germany.

* Reprint requests and correspondence: Dr. Stephan Achenbach, University of Erlangen, Department of Internal Medicine II (Cardiology), Ulmenweg 18, Erlangen, NA 91054 Germany (Email: stephan.achenbach{at}uk-erlangen.de).

Manuscript received January 6, 2009; accepted January 16, 2009.


   REFERENCES
Top
 Abstract
 New Technology
 Diagnosis of CAD
 Imaging of Viability
 Prognosis/Risk Stratification
 New Guidelines and Statements
 REFERENCES
 

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