Author + information
- Received October 3, 2010
- Revision received December 27, 2010
- Accepted January 2, 2011
- Published online April 26, 2011.
- ↵⁎Reprint requests and correspondence:
Dr. Raymond J. Gibbons, Mayo Clinic, Gonda 5, 200 First Street, SW, Rochester, Minnesota 55905
This review is a sequel to our 6 previous reports highlighting the most important published research regarding single photon-emission computed tomography (SPECT), myocardial perfusion imaging, cardiac positron emission tomography (PET), cardiac computed tomography (CT), and cardiac magnetic resonance imaging (MRI). This report covers the English-language research between July 1, 2009, and June 30, 2010. At the suggestion of the editors, we have chosen to be more selective in our coverage and to provide more in-depth discussion of fewer reports. We continue to believe that an integrated, multimodality imaging approach is optimal for the solution of clinical problems, and we have organized the summary around topical themes.
Despite its proven clinical utility, SPECT myocardial perfusion imaging has major technical limitations: low count rates, suboptimal spatial resolution, and relatively long imaging acquisition times. Newer technology based on solid-state cadmium telluride crystals offers promise to address these deficiencies. During this past year, Sharir et al. (1) reported a larger multicenter study comparing images acquired with a new high-speed camera based on this crystal technology with images from conventional SPECT cameras in 238 patients at 4 different U.S. centers.
The total quantitative perfusion defect size at stress and rest correlated closely using both the high-speed SPECT camera and the conventional SPECT camera (r = 0.95 and 0.97, respectively). There was also good concordance in the 3 vascular territories (kappa ≥0.70 for all 3 territories). Bland-Altman analysis showed modest differences in total perfusion defect size between high-speed SPECT and conventional SPECT (Fig. 1). The average amount of ischemia by high-speed SPECT in high-likelihood patients was significantly larger than by conventional SPECT, but there was no comparison with coronary angiography or outcomes. In a perceptive accompanying editorial, Wackers (2) described the promise of this new camera and emphasized the importance of further studies with external validation using coronary angiography and clinical outcomes.
Rapid advances in CT technology continue. The addition of detector rows in multidetector CT makes acquisitions faster, as larger imaging fields are covered in each gantry rotation. Last year, a 320-detector row scanner was introduced, which has a wide enough detector array that the entire heart can be covered in 1 gantry rotation with no table movement. This allows for decreased scan times, though at the potential cost of decreased image quality because of increased scatter.
In a feasibility study, Dewey et al. (3) performed coronary computed tomographic angiography (CTA) in 30 patients scheduled for clinically indicated invasive coronary angiography. Their 320-detector row CTA technique showed excellent sensitivity and specificity on both a per patient and a per segment basis. The average coronary CTA radiation dose was low at 4.2 mSv, which was lower than the average radiation dose of invasive angiography, which was 8.5 mSv (p < 0.05). Coronary CTA also required less contrast than invasive angiography (80 ml vs. 111 ml, p < 0.001). Patients all underwent beta-blockade to heart rates ≤65 beats/min. The small study group was composed of relatively young (mean age 61 years), relatively lean (mean body mass index 26 kg/m2), stable outpatients. Nevertheless, this study showed promise for the use of 320-detector coronary CTA as a possible method for reducing radiation dose while producing diagnostic images.
In MRI, the strength of the signal is proportional to the scanner's magnetic field strength. Higher field strength (3.0-T) MRI scanners have had clinical application in neurologic and musculoskeletal imaging. However, in cardiac imaging, higher field strengths have been associated with a variety of challenges and limitations, including electrocardiographic (ECG) gating. The scanner's magnetic field causes interference with the ECG signal. This is accentuated at higher field strengths and has made ECG gating problematic.
To solve this problem, Frauenrath et al. (4) created an MRI cardiac gating system that triggers from acoustic heart tones rather than electrical signal. In 10 volunteers, they performed several cardiac MRI acquisitions at 3.0-T and found that their acoustic gating system produced fewer artifacts from mistriggered gating than an ECG-gated system. However, even if cardiac gating is solved, a variety of other MRI artifacts are accentuated at 3.0-T compared with 1.5-T. For widespread clinical cardiac application, these will have to be addressed.
General radiation risk
The public health implications of the growth of imaging procedures using ionizing radiation were brought to attention in a landmark study by Fazel et al. (5) that we reported last year. A phantom study by Einstein et al. (6) demonstrated the importance of using current tissue-weighting factors and appropriate conversion coefficients to avoid underestimation of the radiation dose.
In response to the public concern about radiation, practitioners of cardiac CT have sought to reduce the radiation dose for the procedure. This year, 3 distinct techniques for radiation dose reduction were prominent: 1) prospective ECG triggering; 2) high-pitch scanning; and 3) tube voltage reduction.
Prospective ECG Triggering
Prospective ECG triggering is a sequential technique that uses the ECG tracing to initiate acquisition of a single, nonhelical CT dataset of the heart. Depending on the coverage in each rotation, several acquisitions may be needed to cover the entire heart. Because the x-ray beam is on only during the cardiac phase of interest, radiation doses using this technique are much lower than conventional retrospective ECG-gated techniques.
Bischoff et al. (7) evaluated the potential impact of prospective ECG triggering on radiation dose and image quality. Radiation dose was reduced significantly (Fig. 2). Subsequent image quality was preserved. Patients studied with prospective triggering had significantly lower heart rates than patients studied with retrospective gating, demonstrating a potential limitation of prospective ECG triggering: it is typically more heart rate dependent than retrospective gating. As prospective triggering gains acceptance in clinical practice, patients with high heart rates, particularly those who cannot be rate controlled, may become a concern.
High-Pitch Spiral CTA
High-pitch CTA is another technique in cardiac CT that relies on prospective triggering from the ECG signal to reduce radiation dose. The main difference between this technique and other prospectively triggered techniques is that a helical, rather than sequential, CT acquisition is performed during a single R-R interval, rather than across multiple heart beats.
The key to this recent innovation is a dual-tube and detector array system that can be operated at very high-pitch settings (3.0 to 3.4) compared with conventional systems. Scanning at very high pitch allows coverage of the entire heart in under 300 ms with no scan overlap. Radiation exposure is therefore much lower. Achenbach et al. (8) evaluated image quality and radiation dose in 50 consecutive patients with coronary CTA performed using high-pitch scanning. Using a subjective assessment of coronary artery image quality, they found overall excellent image quality in 94% of coronary artery segments (694 of 742); only 4 segments in 3 patients were unevaluable. Unfortunately, more than one-fourth (19 of 69) of the patients initially considered for the study had to be excluded because of heart rate or weight. Estimated radiation dose was <1 mSv (range 0.78 to 0.99 mSv) in all patients (Fig. 3).
Prospective ECG Triggering in Clinical Practice
Not all patients encountered in clinical practice have stable, low heart rates, and not all patients with elevated heart rates will tolerate or respond to pharmacologic rate control.
Pflederer et al. (9) tried to address this limitation using a staged protocol. Patients whose prospectively triggered coronary CT angiograms were not of diagnostic quality received additional conventional spiral CT scans. Although roughly one-fifth of the patients randomized to the prospective ECG gated group required repeat scanning (11 of 56), the overall radiation dose to this group was still significantly lower than that to the control group, which underwent single retrospectively gated CT scans. This staged approach is a potential real-world solution to a common clinical problem. However, the patients in this study who required repeat scanning received approximately 75 ml of extra contrast media, which would limit this approach in patients with renal dysfunction.
Tube Voltage Reduction
Another approach to decrease CT radiation dose is reduction of tube voltage. Previously, typical tube voltage settings for normal-sized adult patients had been about 120 kV. However, several recent studies have shown that adequate image quality can be attained using reduced tube voltage settings of about 100 kV. The lower energy photons used by this technique have the added benefit of increasing the visualization of iodinated contrast and thereby improving image quality.
In a subgroup analysis, Bischoff et al. (10) compared radiation dose and image quality of coronary CT angiograms performed at 100 kV (n = 82) to coronary CTA performed at 120 kV (n = 239). As expected, radiation dose was significantly lower using the reduced tube voltage, approximately 6 mSv for the 100-kV setting compared with 14 mSv for the 120-kV scans. Although image noise increased by 26.3% for the lower voltage scans, signal intensity also increased; signal-to-noise ratios were therefore equivalent between the 2 groups. Of more importance, the investigators found no difference in image quality. Because patients were not prospectively randomized between the 2 groups, the patients in the 100-kV group had lower body weights and body mass indexes than those in the 120-kV group. Lower energy photons have less penetrating power than those produced at higher energy; the investigators therefore recommended restricting the use of low-voltage tube current to nonobese patients.
Diagnosis: Coronary Artery Disease
Adenosine Stress Myocardial Imaging Using CT
Although cardiac CT has gained acceptance in recent years as a test for the assessment of obstructive coronary artery disease (CAD), the physiologic significance of a strictly anatomic finding has been debated. The potential ability of CT to provide both anatomic and physiologic information has been evaluated previously. This year, 2 studies added to those data by combining adenosine-induced stress perfusion imaging with coronary CTA.
In 35 patients with high suspicion of coronary atherosclerosis, Rocha-Filho et al. (11) evaluated the ability of CTA and adenosine stress perfusion CT, both alone and in combination, for the diagnosis of obstructive coronary disease on invasive coronary angiography. First, the CTA images were graded for stenosis (mild [<50%], moderate [50% to 69%], or severe [>70%]). Then the adenosine stress and rest CT images were evaluated for perfusion defect extent and reversibility (fixed, partially reversible, or completely reversible). Finally, the readers were allowed to reclassify the lesions they had initially graded based on CTA images alone. During this final step, vessels previously graded as uninterpretable were considered diseased only if there was a corresponding perfusion defect in the appropriate vascular territory.
The initial diagnostic performance of coronary CTA to detect 50% stenosis on invasive angiography was as follows: sensitivity 83%, specificity 71%, positive predictive value 66%, and negative predictive value 87%. After reclassification based on the perfusion data, each of these metrics improved (sensitivity 91%, specificity 91%, positive predictive value 86%, and negative predictive value 93%). The area under the receiver-operating characteristic curve also improved significantly, from 0.77 to 0.90 (p = 0.003). Findings were similar for the detection of 70% stenosis: all parameters of diagnostic performance improved after reclassification. These gains were present on both a per vessel and a per patient basis but more impressive on a per vessel basis. The investigators took all appropriate steps to limit radiation exposure, including using prospective triggering for the resting CTA, tube current modulation for the stress perfusion study, and appropriate tube voltage for both portions. The total effective radiation dose for the combined study was 11.8 ± 4.5 mSv, which is similar to published estimated dose levels for conventional retrospective ECG-gated coronary CTA. Of the 768 subjects eligible for enrollment in the study, almost one-half (n = 356) declined. An additional 294 patients were excluded because of an inability to comply with or tolerate some part of the scan protocol. For this protocol to gain widespread clinical acceptance, a larger proportion of eligible patients will need to be able to participate.
The same research group also compared adenosine-induced stress myocardial perfusion CT with conventional nuclear stress testing. Blankstein et al. (12) used a similar CT protocol to that described above, with the addition of a delayed prospective ECG-triggered CT 7 min after contrast administration for the detection of delayed hyperenhancement. The investigators again took appropriate steps to limit radiation dose. The total effective radiation dose from their CT protocol (including the delayed images) was 12.7 ± 4.0 mSv. The SPECT studies, performed with 10 mCi of 99mTc sestamibi for the rest study and 30 mCi 99mTc sestamibi for the stress study, had a similar total effective radiation dose (12.7 ± 0.4 mSv, p = 0.99).
Although the stress/rest CT protocol was not optimized for visualization of the coronary arteries (heart rates were high and nitroglycerin was not administered), diagnostic accuracy for the detection of obstructive coronary artery stenosis was very similar to that of SPECT. The sensitivity and specificity of CT for stenosis ≥70% on invasive angiography were 94% (range 71% to 100%) and 41% (range 18% to 67%), respectively, on a per patient basis. Sensitivity and specificity values for SPECT were exactly the same. On a per vessel basis, the sensitivity and specificity of CT for stenosis ≥70% were 86% (range 65% to 97%) and 68% (range 56% to 78%), respectively, compared with 73% (range 50% to 89%) and 73% (range 61% to 82%) for SPECT. In addition, on a per patient basis, the ability of CT delayed enhancement to detect resting perfusion defects on SPECT was reasonable, with sensitivity of 82%, specificity of 81%, positive predictive value of 82%, and negative predictive value of 81%.
Patients With and Without CAD
MRI delayed enhancement is an accepted measure of myocardial fibrosis, whether from infarction or from other causes. Several small studies have previously shown that the presence and amount of delayed enhancement are prognostically significant in specific populations, such as patients with dilated cardiomyopathy. In a much larger study this past year, Cheong et al. (13) studied 857 patients, some with CAD and some with a variety of cardiomyopathies, who underwent cardiac MRI with delayed enhancement and were followed for a mean of 4.4 years. Delayed enhancement was quantified using a “scar index,” which was the average transmurality score of the delayed enhancement over 17 segments.
In both patients with CAD and those without CAD, scar index was associated with cardiac transplantation and/or death on both a univariate basis (p < 0.0001) and a multivariate basis (hazard ratio [HR]: 1.26; p < 0.0001), after adjustment for multiple clinical variables (Fig. 4). Thus, the MRI assessment of scar is prognostically important in broad populations.
In a population of patients with CAD only, Kelle et al. (14) followed 177 patients with known chronic myocardial infarction (MI) for 20.3 ± 13.3 months for all-cause mortality or new MI. These patients underwent MRI with delayed enhancement and assessment of wall motion at rest and with low-dose (10 μg/kg) dobutamine. Many variables were individually associated with all-cause mortality: left ventricular (LV) ejection fraction (EF) (p = 0.026), LV end-systolic volume (p = 0.002), LV end-diastolic volume (p = 0.0004), number of dysfunctional segments at rest (p = 0.003), and semiquantitative wall motion score at rest (p = 0.017).
The change in wall motion score from rest to low-dose stress was not predictive of overall events in their chronic MI population (p = 0.134). However, in the subpopulation of patients with large infarcts (≥6 segments), the improvement in wall motion score from rest to stress (i.e., contractile reserve) was associated with increased events on univariate analysis (p = 0.008). This is consistent with previous published research using other modalities: in patients with ischemic cardiomyopathy, the event rate is increased if there is demonstrable viable myocardium that is not treated with revascularization (15). In addition, patients with large infarcts had lower event-free survival compared with those with smaller infarcts, which is consistent with previous research showing worse survival with increasing infarct size (16).
Steel et al. (17) followed 254 patients with stable angina who underwent clinical adenosine stress MRI myocardial perfusion imaging for a mean of 17 months (range 8 months to 4.7 years). The presence of an MRI-demonstrated reversible perfusion defect was associated with the combined endpoint of cardiac death or MI on both univariate (p < 0.0001) and multivariate analysis (HR: 10.92; p < 0.0001) after adjusting for clinical variables including age, sex, clinical risk factors, and LVEF. Likewise, delayed enhancement also showed univariate (p < 0.0001) and multivariate (HR: 8.09; p < 0.0001) association with death or MI.
Three separate retrospective studies examined the relationship of delayed enhancement to outcomes over a mean of about 3 years in hypertrophic cardiomyopathy (Table 1) (18–20). All 3 studies found a significant univariate association between delayed enhancement and outcome. Bruder et al. (18) and O'Hanlon et al. (19) found multivariate association with their endpoints, and Rubinshtein et al. (20) did a limited, sequential bivariate analysis. The findings of all 3 studies suggest that MRI delayed enhancement may eventually be incorporated into recommendations for implantable cardioverter-defibrillator (ICD) placement in hypertrophic cardiomyopathy.
Last year, several investigators studied infarct size and measures of microvascular obstruction by MRI to predict subsequent adverse remodeling after acute MI (21,22). This year, several studies used MRI measures of myocardial salvage to predict events, particularly after ST-segment elevation MI (STEMI). In these patients, the myocardium at risk is defined as edematous myocardium detected with an MRI sequence (T2-weighted, triple inversion recovery).
Eitel et al. (23) studied 208 patients with STEMI, performing MRI at baseline and clinical follow-up at 6 months for a combined endpoint of death, reinfarction, and new congestive heart failure. Using MRI, they defined a myocardial salvage index as (myocardium at risk − infarcted myocardium)/myocardium at risk. After 6-month follow-up, they found that patients with higher myocardial salvage indexes had fewer events on both univariate (p < 0.001) and multivariate (p < 0.001) analysis (Fig. 5). Most notably, on multivariate analysis, the myocardial salvage index remained associated with events, while 6 other established predictors—Killip class on admission, Thrombolysis In Myocardial Infarction flow grade after percutaneous coronary intervention, LVEF, ST-segment resolution, late microvascular obstruction by MRI, and infarct size by MRI—were not.
In a similar study, Masci et al. (24) studied the same myocardial salvage index in 137 patients with STEMI. They found that myocardial salvage index predicted an increase in LV end-systolic volume at 4 months (odds ratio: 0.64; p = 0.001) after adjustment for multiple clinical and MRI parameters.
CT. Acute MI
In a noteworthy animal study, Mahnken et al. (25) showed that myocardial edema could be detected on noncontrast CT, using MRI as a reference standard (Fig. 6). This suggests that a myocardial salvage index could possibly be calculated using CT.
CTA for CAD
The prognostic value of coronary CT remains a hot topic. Historically, the majority of the research in this area has centered on coronary calcification; however, in recent years, several small studies have examined the potential prognostic utility of coronary CTA. That trend continued this year with larger studies with longer follow-up.
Russo et al. (26) compared the prognostic value of coronary CTA with that of coronary calcium scoring and clinical risk factors. They followed 441 patients who underwent coronary calcium scoring and coronary CTA using 16-detector row CT for an average of just under 3 years (31.9 ± 14.8 months). Patients were evaluated for “hard” cardiac events (cardiac death, nonfatal MI, and unstable angina requiring hospitalization). The patients were grouped into 3 categories according to their coronary calcium scores: ≤10, 11 to 400, and >400. Grading of the coronary CT angiograms was somewhat more complicated but basically consisted of evaluating each coronary artery segment for atherosclerotic plaque (none, calcified, noncalcified, and mixed) and stenosis (none, <50%, or ≥50%). There were a total of 44 hard events during the follow-up period (10%), including 15 cardiac deaths (3.4%), 11 nonfatal MIs (2.5%), and 18 hospitalizations due to unstable angina (4.1%).
Patients with normal coronary arteries on coronary CTA had a very low rate of hard cardiac events (annualized event rate 0.88%) compared with patients with any coronary lesions (annualized event rate 3.89%). Obstructive coronary disease (p = 0.003) and the presence of noncalcified or mixed plaque (p < 0.0001) were independent predictors of hard cardiac events on multivariate analysis. The presence of noncalcified or mixed plaque improved the prediction of hard events (p < 0.0001, chi-square = 27.07) compared with calcium score and clinical pre-test likelihood.
van Werkhoven et al. (27) looked at the incremental prognostic value of coronary CTA compared with coronary calcium studies alone. They followed 432 patients who underwent coronary calcium scoring and coronary CTA using 64-detector row CT for an average of about 2 years. They used a composite endpoint of all-cause mortality, nonfatal MI, and unstable angina requiring revascularization. Patients were stratified into 5 groups by coronary calcium score: 0, 1 to 99, 100 to 399, 400 to 999, and ≥1,000. Coronary CTA results were divided into 3 categories: 1) normal (which included patients with minimal wall irregularities but <30% stenosis); 2) nonsignificant coronary atherosclerosis (coronary artery plaque, but no stenosis >50%); and 3) significant coronary atherosclerosis (stenosis >50%). All diseased segments were evaluated for calcified, noncalcified, and mixed plaque.
There was a total of 21 events (4.9%), including 6 deaths (1.4%), 8 nonfatal MIs (1.8%), and 7 coronary revascularizations for unstable angina (1.6%). Multivariate analysis demonstrated that extent of disease and plaque characteristics were predictive of cardiac events; specifically, plaque burden (number of diseased segments) and plaque composition (number of noncalcified and mixed plaques) provided incremental prognostic value over clinical variables and coronary calcium scoring.
Twenty percent of patients with coronary calcium scores of zero had noncalcified plaque, and 4% of patients with no coronary calcium had significant CAD (stenosis >50%) by CTA. Thus, coronary calcification studies alone may not be adequate to accurately assess prognosis.
Chow et al. (28) studied the prognostic value of coronary CTA both as a measure of CAD severity and also as a measure of LVEF in a single examination. A total of 2,076 consecutive patients without histories of coronary revascularization, heart transplantation, or congenital heart disease underwent coronary CTA on 64-detector row scanners and were followed for 16 ± 8 months. On the basis of the coronary CTA, patients were classified into 4 categories of CAD severity: 1) no visible coronary atherosclerosis; 2) nonobstructive atherosclerosis; 3) non–high-risk obstructive coronary atherosclerosis; and 4) high-risk obstructive CAD, which was defined as left main stenosis ≥50% or 2- or 3-vessel stenoses ≥70% as defined by coronary CTA. LVEF was calculated from CT-derived LV and end-diastolic and end-systolic volumes.
Overall, there were 34 events, including 11 cardiac deaths (0.5%) and 23 nonfatal MIs (1.1%). The only cardiac death in patients with no visible atherosclerosis was in 1 patient with a primary cardiac neoplasm, which led to an event rate of 0.2% (1 of 591) in this group. Thus, lack of visible atherosclerosis on coronary CTA is associated with an excellent prognosis. Multivariate analysis showed that the 4-point CAD severity scoring system by Chow et al. (25) was an independent predictor of cardiac death or nonfatal MI after adjusting for clinical characteristics including National Cholesterol Education Program Adult Treatment Panel III risk and pre-test likelihood of CAD (p < 0.001). As expected, CT-derived LVEF was also an independent risk factor for cardiac death or nonfatal MI (p = 0.001). Assessment of incremental prognostic value showed that CAD severity had incremental prognostic value over clinical predictors, with an increase in the global chi-square value from 24.97 to 43.81 (p < 0.001). LVEF had incremental prognostic value over a model including both CAD severity and clinical predictors, with an increase in the global chi-square value from 43.81 to 54.48 (p = 0.001). This is the latest in a series of studies showing that a variety of variables can be extracted from cardiac CT that give a large amount of prognostic information.
SPECT. Chronic CAD
The clinical use of stress SPECT myocardial perfusion imaging is based on a strong evidence base supporting its prognostic value. Although most of the evidence is based on patients who are younger than 75 years of age, clinical practice is increasingly dominated by older patients. The published evidence on “elderly” patients, usually defined as age 75 years or older, was limited to small studies until Hachamovitch et al. (29) reported this past year on 5,200 elderly patients, with 2.8 ± 1.7 years of follow-up after stress SPECT. Forty-one percent of the patients underwent exercise stress, and 59% underwent pharmacologic stress. The presence of either ischemic or fixed defects conveyed a worse prognosis. Patients with normal results had a lower rate of subsequent cardiac death, which was 1.3% per year. This was higher than the <1% per year that is commonly associated with normal results and cited in clinical practice guidelines (30), reflecting the advanced age of the population. However, Hachamovitch et al. (29) were able to identify important subsets of patients (e.g., those age 75 to 84 years, those with normal resting ECG results, and those undergoing exercise stress) for whom normal results implied a <1% per year rate of cardiac death (Fig. 7). In contrast, patients age 85 years or older, and those who underwent pharmacologic stress, had annual cardiac death rates of 2.3% to 3.7%. Age, perfusion data, and ejection fraction were all independently significant prognostic factors.
SPECT Perfusion and Metaiodobenzylguanidine (MIBG): Sudden Cardiac Death
Sudden cardiac death remains an important clinical and public health problem. Although ICD therapy has improved the survival of patients with abnormal ejection fractions, the majority of sudden cardiac deaths still occur in the much larger population of patients with normal ejection fractions. Piccini et al. (31) published a provocative analysis of the potential value of stress SPECT in 4,865 patients with coronary disease and ejection fractions >35% from the Duke databank. During a mean follow-up period of 6.5 years, there were 161 sudden cardiac deaths (3.3%). Although the summed stress score was independently associated with sudden cardiac and added significantly to the concordance index, a rigorous analysis of reclassification showed that SPECT data did not add any significant net reclassification.
Even in patients with abnormal ejection fractions, there is a need to better identify those who are at the greatest risk and would therefore benefit the most from ICDs. Previous efforts focused on QT and heart rate variability, T-wave alternans, and biomarkers have not achieved success. One potential approach that has not yet been fully explored is cardiac imaging with the norepinephrine analog MIBG. Two important studies during the past year evaluated the potential value of cardiac MIBG imaging. Boogers et al. (32) performed MIBG imaging before ICD placement in 116 patients with heart failure, who were then followed for 23 ± 5 months. One hundred three of the ICDs (89%) were placed for primary prevention; 13 (11%) were placed after cardiac arrest. The majority of the patients (74%) had ischemic cardiomyopathies. The MIBG defect score assessed by SPECT on a late (4 h) SPECT scan was significantly associated with the primary endpoint of appropriate ICD discharge on both univariate and multivariate analysis, but the late MIBG heart-to-mediastinal ratio (H/M) on planar imaging was not.
Jacobson et al. (33) reported a much larger multicenter study of MIBG imaging in 961 patients with New York Heart Association functional class II or III heart failure and ejection fractions ≤35%. Patients with previous defibrillation for cardiac arrest were excluded. The primary analysis was based on the planar H/M ratio using a prospectively designated cutoff of 1.6. The primary endpoint was progression of heart failure, life-threatening arrhythmia, or death. The H/M ratio had an HR of 0.40 (p < 0.01) for this combined endpoint, as well as an HR of 0.14 (p = 0.006) for the endpoint of cardiac death. However, most patients (80%) had abnormal H/M ratios. Surprisingly, SPECT MIBG defect score was not associated with the primary endpoint.
Thus, although both Booger et al. (32) and Jacobson et al. (33) reported positive findings, the 2 studies are inconsistent with respect to which MIBG parameter or imaging technique is most valuable. Further studies are clearly needed before widespread clinical application.
Structure and Function
A majority of MIs occur as a result of plaque rupture, prompting the search for a noninvasive method of identifying so-called vulnerable plaque. Various patient populations have been studied by CTA in an attempt to determine the significance of different plaque morphology. This year, 3 notable studies evaluated the CT characteristics of coronary lesions in patients with known coronary atherosclerosis.
CTA for Evaluation of Thin-Cap Fibroatheroma
Recent studies have suggested that thin-cap fibroatheroma is a precursor lesion for plaque rupture. Optical coherence tomography provides a semi-invasive method of detecting this thin-cap fibroatheroma. Kashiwagi et al. (34) compared coronary CTA performed with 64-detector row CT with optical coherence tomography for the detection of thin-cap fibroatheroma in 105 patients with known CAD (31 with acute coronary syndromes and 74 with stable angina pectoris).
Culprit lesions were identified in all patients using a combination of ECG, echocardiographic, and nuclear scintigraphic findings, in combination with stenotic site by coronary angiography. Patients were divided into 2 categories: those with thin-cap fibroatheroma of the culprit lesion seen by optical coherence tomography (n = 25) and those without (n = 80), although identifying culprit lesions in this manner can be problematic.
Findings on coronary CTA that were predictive of thin-cap fibroatheroma were 1) positive remodeling; 2) low-attenuation plaque; and 3) ringlike enhancement. The first 2 characteristics confirm the results of previous CT studies of coronary plaque. To our knowledge, the association of peripheral ringlike enhancement with vulnerable coronary atheroma has not previously been demonstrated in vivo in patients by CT, although plaque enhancement or inflammation has been shown by other modalities, particularly in the carotid arteries (35,36). The pathophysiology of ringlike enhancement is unknown.
A total of 38 patients had to be excluded from the study, mostly because of heavy coronary calcification that precluded evaluation. If a significant number of patients with known CAD are not suitable candidates, the applicability of this technique in clinical practice would be limited.
CTA features of culprit lesions in STEMI and non-STEMI
Huang et al. (37) performed coronary CTA using 64-detector row CT in 120 patients with acute coronary syndromes to examine differences in culprit lesion plaque morphology between patients with STEMI (n = 54) and those with non–ST-segment elevation myocardial infarction (NSTEMI) (n = 66). As in the prior study, culprit lesions were identified using a combination of imaging modalities with correlation to invasive angiography.
Culprit lesions in patients with STEMI were more stenotic than those in patients with NSTEMI. Culprit lesions in patients with STEMI also exhibited more positive remodeling than those in patients with NSTEMI, in terms of both the amount of remodeling per lesion (remodeling index 1.28 ± 0.34 vs. 1.16 ± 0.22, p = 0.21) and the total percent of culprit lesions exhibiting any positive remodeling (81.5% vs. 63.6%, p = 0.031). Although the overall calcium scores of patients with STEMI and those with NSTEMI were not significantly different, patients with STEMI had an increased total plaque burden (0.91 ± 0.10 vs. 0.84 ± 0.12) and a lower average plaque density (25.8 ± 13.9 vs. 43.5 ± 19.1 Hounsfield units [HU], p < 0.001) per lesion than patients with NSTEMI. However, as in the study by Kashiwagi et al. (34), identifying culprit lesions can be difficult, especially when there is more than 1 lesion in a particular vessel territory. Lesions are often selected in terms of their morphology, which can bias the results of studies such as this one and the one by Kashiwagi et al. (34).
Plaque Characteristics Predict Post-Procedural Myocardial Injury
Uetani et al. (38) used a semiautomated tool for plaque analysis to characterize and quantify atherosclerotic lesions seen on coronary CTA in 189 patients who subsequently underwent coronary artery stenting. They then correlated the CT findings with the presence of post-procedural myocardial injury, defined as troponin T elevation ≥0.1 ng/ml, which was seen in 59 patients (31.2% of the study population).
On 64-detector row CT, the lesions of interest were measured and plaque composition was determined on the basis of HU values (low-attenuation plaque <50 HU, moderate-attenuation plaque 50 to 150 HU, high-attenuation plaque >500 HU). The arterial lumen was defined as 151 to 500 HU. The volume of low-attenuation plaque and the portion of total plaque that represented low-attenuation plaque were significantly higher in patients with post-procedural myocardial injury than in those without (87.9 ± 94.8 mm3 vs. 47.4 ± 43.7 mm3, p < 0.01, and 32.9% vs. 29.0%, p < 0.01, respectively). However, there was significant overlap between the 2 groups.
Incidental, noncardiac findings on images obtained during cardiac CT continue to be of interest. This year, 2 studies examined the potential importance of these findings in much larger populations than previously reported. Johnson et al. (39) evaluated coronary CT angiograms from 6,920 consecutive patients and found at least 1 extracardiac finding in 1,642 (23.7%), 1,119 of which (16.2% of the total group) were significant enough to require therapy or additional testing. In 99 patients, immediate therapy was required to treat significant medical conditions; new diagnoses of malignancy were made in 5 patients.
Kim et al. (40) performed a retrospective review of 12,268 cardiac CT scans performed on 11,176 patients and found 61 patients with lung cancer, 36 of whom had initial diagnoses by cardiac CT. Of these 36, 32 (89%) would not have been detected using a limited field of view (16 to 18 cm), sometimes recommended for coronary CT (Fig. 8).
LV Volumes and Mass
MRI can measure cardiac volumes very precisely. Because MRI uses no ionizing radiation, it can be used in large population studies, such as MESA (Multi-Ethnic Study of Atherosclerosis), an ongoing multicenter study of subjects with subclinical atherosclerosis.
Although severe chronic obstructive pulmonary disease is known to lead to elevated pulmonary vascular resistance, with an associated decrease in LV filling, the effect of nonsevere lung disease on LV function is not known. In 2,816 subjects, Barr et al. (41) compared LV volumes by MRI with emphysema quantified on CT scans in subjects without severe lung disease. On average, the patients had 15% of their lungs affected by emphysema on CT but normal average spirometric lung function. Increasing emphysema score by CT was associated with decreased LV end-diastolic volume, end-systolic volume, and cardiac output as measured by MRI; the strength of the association was greater for smokers.
Thus, subclinical changes in lung architecture, possibly leading to a loss of the pulmonary capillary bed, were associated with subclinical abnormal LV filling.
MRI has long been used for the evaluation of systolic function using LVEF and regional wall motion. More recently, MRI has been used to evaluate diastolic function, using either measurements of flow through the mitral valve, as is done in echocardiography, or LV volume curves, as is done with nuclear methods. Several investigators used various MRI parameters to evaluate patients with diastolic dysfunction.
Patel et al. (42) studied 201 patients with end-stage renal disease with LV hypertrophy by MRI and followed them for 3.6 years (range 1.2 to 5.2 years) for all-cause mortality. The investigators measured left atrial volume from magnetic resonance images using the biplane area-length method. Increasing left atrial volume was individually significantly associated with increased all-cause mortality (p = 0.01). In multivariate analysis, left atrial volume remained associated with all-cause mortality (HR: 1.06; p = 0.009), along with LVEF (HR: 1.77; p = 0.05), the presence of ischemic heart disease (HR: 2.73; p < 0.001), and kidney transplantation (HR: 0.22; p < 0.001).
Left atrial enlargement in these patients may be caused by diastolic dysfunction and chronic fluid overload; the investigators suggested its use as a prognostic marker in patients with end-stage renal disease. Echocardiographic left atrial volume has been well recognized as a poor prognostic sign (43). However, MRI measurements should theoretically be more precise.
Other investigators have also used MRI to evaluate different aspects of diastolic function. Kawaji et al. (44) developed an automated method for quickly quantifying LV volumes across the cardiac cycle and used the resultant filling curves to generate diastolic filling indexes (Fig. 9). This has been done previously with radionuclide angiography. The MRI filling indexes correlated with New York Heart Association functional class (p = 0.004) and had 90% specificity and 74% sensitivity for detecting diastolic dysfunction defined by echocardiographic E/A ratios.
Rijzewijk et al. (45) compared MRI-measured flow through the mitral valve with a variety of parameters of diastolic function, including E/A ratios and peak E-wave deceleration. They compared findings between 78 men with uncomplicated type 2 diabetes and 24 normoglycemic controls and found that the patients with diabetes had significantly elevated E/A ratios (p = 0.003). They also performed a comprehensive analysis of fatty metabolism with PET and phosphorus metabolism with MRI spectroscopy and found increased (p = 0.021) fatty acid metabolism in the patients with diabetes.
Moreo et al. (46) compared known Doppler echocardiographic findings of diastolic dysfunction with MRI findings of myocardial fibrosis. In 252 subjects undergoing Doppler echocardiography and MRI delayed enhancement imaging, including normal controls and patients with a variety of cardiomyopathies, patients with diastolic dysfunction were more likely to have myocardial fibrosis by MRI than patients without diastolic dysfunction (p < 0.0001).
MRI-Guided Radiofrequency Ablation
Catheter-based radiofrequency ablation is increasingly used to treat refractory atrial fibrillation. Intraprocedural navigation of catheters is an area of intense interest; many investigators are searching for imaging systems that would permit real-time, 3-dimensional image guidance of the ablation procedure. MRI has definite advantages: a lack of ionizing radiation and excellent soft tissue contrast. However, the major disadvantage of MRI has been the difficulty of creating MRI-compatible equipment, as the MRI scanner generates a continuous, strong magnetic field, which interferes with the function of electronic equipment and potentially heats wires and cables.
Hoffmann et al. (47) developed an MRI-compatible ablation catheter, which they tested in 20 pigs. Catheter position was continually monitored with MRI: an interventionalist guided the catheter while a second operator continually adjusted the imaging planes to follow the catheter. As ablation was performed in the right atrium, the ablated right atrial tissue was detected with MRI using an edema-sensitive sequence. The procedure was considered successful if MRI showed that a continuous ablation line had been created between the inferior aspect of the tricuspid annulus and the insertion of the inferior vena cava. Pigs subsequently went to electrophysiologic testing and then to post-mortem gross examination to evaluate the ablation line.
In the 18 surviving pigs, the ablation line was complete by MRI. In all 18 pigs, post-mortem gross examination confirmed the completeness of the ablation line, although in 3 of these, electrophysiologic mapping suggested that the block was incomplete. The investigators concluded that MRI navigation of radiofrequency ablation is feasible but noted that translation of this work to humans will require further safety testing. This avenue of research is promising for the development of 3-dimensional catheter mapping.
Appropriateness of Imaging
Issues of utilization and appropriateness continued to attract interest in both the scientific and health policy world.
Parker et al. (48) reported on the regional variation in all noninvasive imaging (cardiac and noncardiac) over the past decade in Medicare beneficiaries. The highest use region (Atlanta) had approximately 50% more utilization of noninvasive imaging than the lowest use region (Seattle). Some of the highest regional variation occurred in noninvasive cardiovascular imaging. Echocardiography and cardiovascular nuclear imaging had nearly twice as much utilization in the highest use region compared with the lowest use region. Cardiac MRI and cardiac CT both had more than 7 times the utilization in the highest use region compared with the lowest use region.
Appropriate use criteria, developed by the American College of Cardiology Foundation in association with multiple other partners, are a response to concerns about utilization. Prior studies of the application of appropriate use criteria have come from single centers. Hendel et al. (49) reported a large multicenter study that used a point-of-service Internet-based tool on 6,351 patients at 6 centers. Each of the sites that participated had access to online reports of appropriate, uncertain, and inappropriate tests in real time. However, only 4 of the 6 sites had sufficient data to permit study of the potential changes in the rates of inappropriate tests over 3 different time periods (Fig. 10). One of these 4 sites, which had the highest rate of inappropriate studies at baseline, reported a significant decrease in inappropriate studies. The 5 most frequent inappropriate indications accounted for the vast majority (92%) of the inappropriate studies (Table 2); this finding was very similar to previous single-center reports. This landmark study demonstrated the feasibility of tracking imaging appropriateness over time to target initiatives for physician education and quality improvement.
Levin et al. (50) reported on the impact of a 3-tier prior authorization program of a radiology benefits management company on the utilization of MRI, CT, and PET. The rate of growth of imaging appeared to slow with this program, although accurate baseline data were not available.
Bourque et al. (51) reported a prospective analysis on 1,056 consecutive exercise SPECT patients that is likely to influence future revisions of the appropriate use criteria. Of the 1,056 study patients, 974 exceeded 85% of their maximum age-predicted heart rates. Of these 974 subjects, almost one-half (473 [48.6%]) achieved at least 10 metabolic equivalents of exercise. These patients had a very low prevalence (0.4%) of ischemia (Fig. 11). There was no severe ischemia (≥10% of the left ventricle) in the 430 patients who did not have exercise-induced ST-segment depression. Bourque et al. (51) suggested that the expense of SPECT imaging could be avoided in 31% of all the patients in their laboratory by not injecting tracer in subjects who reached their target heart rates and ≥10 metabolic equivalents of exercise without ischemic ST-segment depression.
Patel et al. (42) reported that only 37.6% of patients undergoing coronary angiography in the National Cardiovascular Data Registry had obstructive CAD and that a “positive result on a noninvasive test was only modestly predictive.” However, 30% of the patients in this study were asymptomatic, and resting electrocardiography, echocardiography, and CT may have been included as noninvasive tests, so the relevance of this study to stress imaging in symptomatic patients is unclear.
We hope that this summary will inspire readers to examine the important reports in more detail and to apply imaging more carefully within their practices.
Dr. Gibbons is a consultant for Molecular Insight Pharmaceuticals, Lantheus Medical Imaging. Dr. Araoz is a consultant for Medtronic. Dr. Williamson is a consultant for Siemens Medical Systems.
- Received October 3, 2010.
- Revision received December 27, 2010.
- Accepted January 2, 2011.
- American College of Cardiology Foundation
- Sharir T.,
- Slomka P.J.,
- Hayes S.W.,
- et al.
- Wackers F.J.
- Dewey M.,
- Zimmermann E.,
- Deissenrieder F.,
- Laule M.
- Bischoff B.,
- Hein F.,
- Meyer T.,
- et al.
- Achenbach S.,
- Marwan M.,
- Ropers D.,
- et al.
- Bischoff B.,
- Hein F.,
- Meyer T.,
- Hadamitzky M.,
- Martinoff S.,
- Schomig A.
- Blankstein R.,
- Shturman L.D.,
- Rogers I.S.,
- et al.
- Cheong B.Y.,
- Muthupillai R.,
- Wilson J.M.,
- et al.
- Kelle S.,
- Roes S.D.,
- Klein C.,
- et al.
- Allman K.C.,
- Shaw L.J.,
- Hachamovitch R.,
- Udelson J.E.
- Gibbons R.J.,
- Valeti U.S.,
- Araoz P.A.,
- Jaffe A.S.
- Steel K.,
- Broderick R.,
- Gandla V.,
- Larose E.
- Bruder O.,
- Wagner A.,
- Jensen C.J.,
- et al.
- O'Hanlon R.,
- Grasso A.,
- Roughton M.,
- et al.
- Rubinshtein R.,
- Glockner J.F.,
- Ommen S.R.,
- et al.
- Eitel I.,
- Desch S.,
- Fuernau G.,
- et al.
- Masci P.G.,
- Ganame J.,
- Strata E.,
- et al.
- Mahnken A.H.,
- Bruners P.,
- Bornikoel C.M.,
- Kramer N.,
- Guenther R.W.
- Russo V.,
- Zavalloni A.,
- Bacchi Reggiani M.L.,
- et al.
- van Werkhoven J.M.,
- Schuijf J.D.,
- Gaemperli O.,
- et al.
- Chow B.J.,
- Wells G.A.,
- Chen L.,
- Yam Y.,
- Galiwango P.
- Hachamovitch R.,
- Kang X.,
- Amanullah A.M.,
- et al.
- Gibbons R.,
- Abrams J.,
- Chatterjee K.,
- et al.
- Piccini J.P.,
- Starr A.Z.,
- Horton J.R.,
- et al.
- Boogers M.J.,
- Borleffs C.J.,
- Henneman M.M.,
- et al.
- Jacobson A.F.,
- Senior R.,
- Cerqueira M.D.,
- et al.
- Kashiwagi M.,
- Tanaka A.,
- Kitabata H.,
- et al.
- Davies J.R.,
- Rudd J.H.,
- Graves M.J.,
- et al.
- Uetani T.,
- Amano T.,
- Kunimura A.,
- et al.
- Moller J.E.,
- Hillis G.S.,
- Oh J.K.,
- et al.
- Kawaji K.,
- Codella N.C.F.,
- Prince M.R.,
- et al.
- Rijzewijk L.J.,
- van der Meer R.W.,
- Lamb H.J.,
- et al.
- Moreo A.,
- Ambrosio G.,
- De Chiara B.,
- et al.
- Hoffmann B.A.,
- Koops A.,
- Rostock T.,
- et al.
- Hendel R.C.,
- Cerqueira M.,
- Douglas P.S.,
- et al.
- Bourque J.M.,
- Holland B.H.,
- Watson D.D.,
- Beller G.A.