YEAR IN CARDIOLOGY SERIES
The Year in Cardiac Imaging
Raymond J. Gibbons, MD*,*,
Philip A. Araoz, MD and
Eric E. Williamson, MD
* Division of Cardiovascular Diseases and Internal Medicine, Department of Medicine, Mayo Clinic and Mayo Foundation, Rochester, Minnesota
Department of Radiology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota
Manuscript received September 6, 2009;
revised manuscript received September 25, 2009,
accepted September 28, 2009.
* Reprint requests and correspondence: Dr. Raymond J. Gibbons, Mayo Clinic, Gonda 5, 200 First Street, SW, Rochester, Minnesota 55905 (Email: gibbons.raymond{at}mayo.edu).
Key Words: cardiac • imaging • diagnostic
This review is a sequel to our 4 previous reports highlighting the most important literature 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 primarily covers the English-language literature between July 1, 2008, and June 30, 2009. It also includes selected papers from JACC: Cardiovascular Imaging between January 1, 2008, and June 30, 2008, which we overlooked in last year's review, as the journal was not yet listed in Index Medicus. The continued growth in cardiac imaging literature, exemplified by the arrival of both Circulation: Cardiovascular Imaging and JACC: Cardiovascular Imaging, has continued to challenge us in reaching decisions as to which articles merit inclusion in this review. We recognize that our decisions will inevitably please some authors and disappoint others. We can assure everyone that we have made every effort to be as objective as possible in reaching these ever more difficult decisions. We believe that an integrated, multimodality imaging approach is optimal for the solution of clinical problems, which is reflected in the organization of this summary around topical themes, and in the preference that we have given to studies that take a multimodality approach.
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Technical Advances
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SPECT.
Advances in gamma camera technology have made more rapid SPECT imaging feasible. Berman et al. (1) reported on their initial experience imaging 374 patients with a high-speed SPECT system and a rapid dual-isotope imaging protocol that was completed in 30 min. Overall image quality was good to excellent, even though rest imaging was begun within 2 min of technetium injection.
PET.
The use of PET for the assessment of perfusion has been limited by the requirement for a cyclotron or a rubidium generator. Sherif et al. (2) reported excellent tracer uptake and image quality with a new fluorine-18–labeled PET perfusion agent, BMS 747158-02, an analog of the insecticide pyridaben, in a rat model of myocardial infarction (MI). The accompanying paper by Camici and Rimoldi (3) clarified the potential importance of this early work.
PET and CT.
There has been an increasing interest in atherosclerosis imaging using PET FDG. Rudd et al. (4) reported on subjects who underwent vascular PET imaging along with CT. There was little overlap between plaque inflammation assessed by PET and calcification assessed by CT, suggesting that calcification may represent the late stage of "burnt-out" atherosclerosis. Wykrzykowska et al. (5) found both coronary artery and aortic FDG uptake in patients with malignancy who underwent PET-CT after a low carbohydrate–high fat diet and reported a weak correlation between FDG coronary uptake and angiographic disease.
CT.
A new 128-row dual-source CT scanner made its debut at the Radiological Society of North America meeting in November 2008. This new scanner allows for very high-pitch spiral CT scanning of the heart, which decreases exposure time, allowing "single-beat" imaging of the coronary arteries. Initial reports of this technology describe very low radiation doses, approximately 1 to 2 mSv for coronary computed tomography angiography (CTA) (6,7).
Early reports also describe another "high-definition" CT scanner that employs a novel detector material and a different reconstruction algorithm as compared with conventional systems. This scanner promises increased spatial resolution and decreased image noise, both of which have been shown to improve visualization of coronary artery stents (8).
MRI.
Over the past year, 2 MRI techniques, which were previously noncardiac, were applied to the heart. Diffusion tensor imaging (DTI) is an MRI technique to measure the natural dispersal of water molecules in tissue. Because water molecules preferentially diffuse along fibers, DTI has been used to image fiber tracts, primarily in the brain (9), but has had only limited use in in vivo clinical populations.
Wu et al. (10) used an in vivo cardiac DTI technique to describe changes in cardiac microstructure in 17 patients 3 weeks and 7 months after MI. Several measures of microstructure integrity were acutely abnormal in myocardium adjacent to the infarct as compared with remote myocardium. Late improvement in wall thickening correlated with improvement in mean diffusivity, one of the microstructure parameters.
In magnetic resonance elastography, tissue is externally vibrated, and MRI is used to directly image the waves propagating in tissue in order to measure stiffness. Increased stiffness in the liver is associated with hepatic fibrosis (11). In a pilot study on normal volunteers, Sack et al. (12) estimated myocardial stiffness using in vivo cardiac magnetic resonance elastography by vibrating the chest and measuring the amplitude of the waves in the left ventricle.
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Viability
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CT.
Cury et al. (13) evaluated cardiac CT in 102 patients (34 ST-segment elevation myocardial infarction [STEMI]; 68 controls) and compared the results with SPECT. Overall, detection of acute MI was very good (sensitivity = 94%, specificity = 97%), but correlation with SPECT infarct size was only moderate (r = 0.48, mean difference = –7 ± 9%).
MRI.
The most established MRI technique for detecting infarcted myocardium is delayed enhancement imaging. Recent studies have focused on delayed enhancement in the acute phase, with emphasis on evaluating peri-infarct border zone areas and myocardium at risk.
Phrommintikul et al. (14) used an MRI method called T2-weighted imaging to measure myocardial edema and identify myocardium at risk. In 15 patients with acute MI, the authors used MRI to define myocardium at risk as edematous, noninfarcted myocardium. At 3-month follow-up, there was a modest correlation between improved systolic wall thickening and myocardium at risk at baseline (r = 0.42, p < 0.01).
O'Regan et al. (15) described the relationship between edematous and infarcted tissue in 15 patients after acute STEMI. The lateral boundaries of edema closely approximated the region of delayed enhancement, (i.e., infarction) suggesting that cardioprotective strategies "may have limited potential for improving myocardial salvage at these infarct margins."
However, Englblom et al. (16) questioned whether acute delayed enhancement accurately represents infarct size or overestimates it by including peri-infarct tissue. In 22 patients with acute MI, delayed enhancement was measured at multiple time points over 1 year. The volume of enhancing myocardium decreased rapidly in the first week and gradually thereafter (Fig. 1). The authors suggested that the initial rapid decrease in delayed enhancement was due to viable, peri-infarct tissue that was not infarcted.
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Figure 1 Change in DE
In this patient with acute myocardial infarction, images at day 1 show transmural delayed enhancement (DE) and akinesis of the anterior wall (arrows). There was a marked decrease in DE at days 1 to 7 (arrows); at 1 year, there is recovery of function despite the transmural DE at baseline (arrows). Modified from Englblom et al. (16). MRI = magnetic resonance imaging.
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Further studies are needed to define the optimal timing and best MRI technique(s) to distinguish infarcted tissue from viable, peri-infarct tissue. This distinction has important implications for clinical treatment, and (hopefully) patient outcomes.
CT and MRI.
MRI has better tissue characterization than CT, and CT delayed enhancement remains at a preliminary stage compared with MRI. However, CT has much higher spatial resolution than MRI, a potential advantage for quantifying areas of heterogeneous delayed enhancement at the perimeter of infarcts, which might be a substrate for arrhythmias (17). Schuleri et al. (18) compared 64-detector CT peri-infarct zone size with MRI peri-infarct size in 15 mini-pigs. Using pathology as a gold standard, MRI underestimated infarct size at very thin slice thickness (0.1 mm), whereas CT did not, suggesting that CT may be useful in quantifying the peri-infarct zone.
SPECT and MRI.
Carlsson et al. (19) compared MRI edema imaging with SPECT for detection of myocardium at risk in 16 patients with STEMI. Following established methodology, Tc-99m tetrofosmin was injected intravenously before percutaneous coronary intervention (PCI), and SPECT images were acquired within hours after PCI. In contrast, the MRI images were performed electively 1 week after PCI (Fig. 2). SPECT and MRI measurements correlated well (r2 = 0.70) with little variation (mean difference in left ventricular [LV] mass –2.3 ± 5.7%). The authors concluded that MRI provided similar information to SPECT with less logistical difficulty.
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Figure 2 Comparison of SPECT to MRI Images
Short-axis single-photon emission computed tomography (SPECT) images obtained in a patient with ST-segment elevation myocardial infarction. The SPECT radiotracer was injected before reperfusion. The defect in the inferior wall shows the myocardium at risk. Increased signal magnetic resonance imaging (MRI) images designed to show edema (T2-STIR) correlated with SPECT defect (r2 = 0.70, p < 0.001). Delayed enhancement cardiovascular magnetic resonance (DE-CMR) images designed to show irreversible infarction were much smaller. Reprinted, with permission, from Carlsson et al. (29).
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Patient Safety
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SPECT/CT/MRI.
Fazel et al. (20) analyzed claims data from 952,420 nonelderly adults in 4 states, and reported moderately elevated radiation doses in 19.4% of enrollees and high doses in 2.1%. SPECT MPI accounted for 22.1% of the total effective dose.
CT.
The radiation dose associated with coronary CTA remains a concern. Raff et al. (21) implemented available dose-reduction strategies in a 15-hospital consortium in Michigan and reduced estimated radiation doses in half without a decrease in image quality (Fig. 3).
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Figure 3 Improvement in Radiation Dose
Distribution of patients by estimated radiation doses in 15 hospital imaging centers in Michigan, before and after introduction of established dose-reduction techniques. Reprinted, with permission, from Raff et al. (21).
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Hausleiter et al. (22) evaluated 1,965 cardiac CT scans performed at 50 international sites to determine radiation exposure in routine clinical practice. Although the mean radiation dose (12 mSv) was reasonable for retrospective electrocardiographic (ECG)-gated CT, there was significant variation in radiation dose between sites with inconsistent application of dose-reduction strategies.
As reported in last year's paper, prospective ECG triggering is gaining acceptance as a means of lowering radiation doses for coronary CTA (Table 1) (23–29).
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Table 1 Studies on 64-Slice Scanners Comparing Radiation Dose for Retrospective Gated CT and Prospective Triggered CT Radiation Dose
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CT and SPECT.
Gerber et al. (30) issued a comprehensive American Heart Association statement on ionizing radiation that emphasized physician education, physician judgment, and efforts to reduce patient dose whenever feasible.
CT and PET.
Hybrid PET–CT imaging has tremendous potential. Javadi et al. (31) reported their initial experience with low-dose, prospectively gated coronary CTA, which reduced radiation exposure by 70% without compromising image quality or integration with PET.
MRI.
Although pacemakers and internal defibrillators have long been absolute contraindications to MRI examinations, several recent studies have suggested that some patients with pacemakers or defibrillators may be able to undergo MRI scanning. Mollerus et al. (32) reviewed 75 noncardiac MRI scans in 40 patients and found no unanticipated device-programming changes, no changes in battery status or capture threshold, and no change in cardiac troponin-I or myoglobin values. Pulver et al. (33) performed cardiac MRI in 11 congenital heart disease patients with epicardial pacing leads. No inappropriate pacing or arrhythmias occurred. Device voltages, thresholds, and lead impedances were similar before and after MRI.
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Coronary Artery Disease (CAD): Diagnosis
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SPECT.
The effect of caffeine on adenosine stress perfusion is a long-standing concern.
Reyes et al. (34) studied the effects of caffeine ingestion (2 cups of coffee) on the magnitude of SPECT perfusion abnormality induced by a standard adenosine dose of 140 µg/kg/min, and a higher dose of 210 µg/kg/min. Caffeine dramatically reduced SPECT defect size after standard adenosine infusion, but not after high-dose infusion (Fig. 4). The authors suggested that patients should be screened carefully for caffeine ingestion prior to adenosine SPECT, and selectively considered for high-dose adenosine infusion.
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Figure 4 Effect of Caffeine on Adenosine Response
Effect of caffeine ingestion on the summed difference score (SDS) by single-photon emission computed tomography perfusion imaging. Individual values, mean, and 95% confidence intervals are shown for (A) standard adenosine infusion (140 µg/kg/min) and (B) high-dose adenosine (210 µg/kg/min). Reprinted, with permission, from Reyes et al. (34).
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Regadenoson is a novel adenosine agonist approved for pharmacologic stress testing. Using the data from 2 multicenter phase 3 trials, Cerqueira et al. (35) reported that regadenoson was equivalent to adenosine in diagnostic efficacy, and better tolerated from a symptomatic standpoint. In an accompanying editorial, Udelson (36) provided important insights from the development programs of the new adenosine agonists.
The dosage used for technetium perfusion agents varies across countries. Notghi et al. (37) reported that the activity injected for 2-day protocols needed to be increased above the usual 400 MBq (10.8 mCi) in the United Kingdom for all patients above 80 kg.
SPECT–CT.
The potential value of combined SPECT and coronary CTA has yet to be fully explored. Husmann et al. (28) reported that coronary CTA provided additional information regarding pre-clinical atherosclerosis in 38 of 85 patients (45%) studied with prospectively gated coronary CTA and stress-only SPECT.
CT.
Ruzsics et al. (38) describe a new method utilizing simultaneous dual-energy cardiac CT to identify cardiac ischemia by determining myocardial iodine content. This method accurately detected myocardial ischemia compared with SPECT (sensitivity = 91%, specificity = 92%) and agreed closely with catheterization for the detection of stenosis (sensitivity = 98%, specificity = 88% per segment) (Fig. 5).
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Figure 5 Dual-Energy CT Images and SPECT
Invasive angiography (A) and coronary computed tomography (CT) (B) demonstrates culprit lesion (arrow) in the first diagonal branch. Dual-energy CT images performed using 140 and 80 kV (C and D) are used to generate a myocardial iodine map (E), which shows a perfusion deficit (arrows) corresponding to findings from single-photon emission computed tomography (F, arrows). Reprinted, with permission, from Ruzsics et al. (38).
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George et al. (39) evaluated adenosine stress perfusion CT as an adjunct to coronary CTA in 40 patients with SPECT perfusion defects. They found good sensitivity and specificity for the detection of obstructive CAD (86% and 92%, respectively) and promising initial results regarding quantification of perfusion abnormalities; however, only 2 of 6 reversible defects seen on SPECT were appropriately characterized using CT perfusion.
Meijboom et al. (40) compared coronary CTA to invasive angiography with measurement of fractional flow reserve. They found a moderate correlation between CTA and invasive angiography for the severity of stenosis (r = 0.53; p < 0.0001), but limited agreement between both modalities and fractional flow reserve (kappa  0.25 for both), suggesting that anatomical imaging may not provide a complete assessment of coronary disease.
Several important multicenter trials comparing 64-row coronary CTA with cardiac catheterization were published this year. In the Core 64 trial, Miller et al. (41) studied 291 patients from 9 centers located in 7 different countries; 56% of the patients had significant CAD. Although they reported a sensitivity of 85% (95% confidence interval [CI]: 79% to 90%) and specificity of 90% (95% CI: 83% to 94%) on a per-patient basis, the negative predictive value was a disappointing 83%, and the authors concluded that "multidetector CT angiography cannot replace conventional coronary angiography at present." In contrast, in the ACCURACY (Assessment by Coronary Computed Tomographic Angiography of Individuals Undergoing Invasive Coronary Angiography) trial, Budoff et al. (42) prospectively analyzed 230 subjects from 16 different sites with a lower prevalence of 14% of significant CAD (70% stenosis). The authors found an overall sensitivity and specificity of 94% and 83% for the detection of 70% stenosis, with a higher negative predictive value of 99%, reflecting the lower prevalence of CAD in their population.
Meijboom et al. (43) evaluated coronary CTA in 360 symptomatic patients from 3 university hospitals (disease prevalence = 68%) and found excellent overall sensitivity of 99% with preserved negative predictive value (97%); however, specificity was relatively low because CTA overestimated the severity of stenosis.
In the NIMISCAD (Non Invasive Multicenter Italian Study for Coronary Artery Disease) trial, Marano et al. (44) enrolled 367 patients from 20 sites in Italy (prevalence of CAD = 56%) and found consistently high negative predictive values of coronary CTA performed on 16-row (91%; n = 264) and 64-row (89%; n = 63) systems.
Along with these multicenter trials, several studies were published comparing newer generations of CT scanner with catheterization (Table 2) (6,45–50).
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Table 2 64-Detector Row Dual-Source Coronary CTA Compared With Catheter Angiography for Detection of >50% Stenoses
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Quantitative stenosis analysis remains an issue for coronary CTA. Dodd et al. (51) compared various CT post-processing methods with quantitative coronary angiography in 29 patients for the evaluation of nonculprit lesions. Although they found good correlation between the 2 modalities for vessels >3 mm in diameter (R = 0.78 to 0.91, p < 0.01), the correlation was poor for calcified lesions (R = 0.01 to 0.20), and 24% of segments with >30% stenosis had to be excluded from analysis.
In the ROMICAT (Rule Out Myocardial Infarction using Computer Assisted Tomography) study, Hoffmann et al. (52) evaluated CT scans in 368 patients with acute chest pain and an inconclusive initial workup. The extent of plaque (area under the curve [AUC] = 0.88) and presence of stenosis (AUC = 0.82) predicted acute coronary syndrome (ACS) independent of cardiovascular risk factors and Thrombolysis In Myocardial Infarction (TIMI) risk score (AUC = 0.63). Fifty percent of patients had no evidence of CAD by CT, a finding that carried 100% sensitivity and 100% negative predictive value for ACS. However, stenosis by CT had limited sensitivity for ACS (77%), and the study had no major adverse cardiac events at 6 months.
MRI.
Several previous studies have shown that MRI may detect clinically unsuspected MIs in asymptomatic patients who are elderly or at risk. In a novel study of 102 male marathon runners age 57 ± 6 years, Breuckmann et al. (53) found that 12 (12%) of the runners had delayed enhancement on MRI, compared with 4% of age-matched controls. The number of marathons completed was an independent predictor of the presence of delayed enhancement, suggesting that the amount of exercise may have "had a role in the development" of delayed enhancement.
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CAD: Prognosis
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SPECT.
The much-anticipated DIAD (Detection of Ischemia in Asymptomatic Diabetics) study reported on the use of adenosine stress SPECT imaging for CAD screening in 1,123 participants with type II diabetes and no symptoms of CAD (54). The cumulative cardiac event rates were low, averaging 0.6% per year, and were not significantly reduced by SPECT screening (Fig. 6), even though participants with normal SPECT or small SPECT defects had lower event rates than those with moderate or large defects.
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Figure 6 Effect of Screening on Clinical Outcomes
Cumulative incidence of cardiac death or nonfatal myocardial infarction for participants in the DIAD (Detection of Ischemia in Asymptomatic Diabetics) study, according to whether they were randomly assigned for systematic single-photon emission computed tomography screening or not. Reprinted, with permission, from Young et al. (54).
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Cantor et al. (55) assessed the impact of mild-to-moderate ischemia (assessed by either SPECT or echo) on patients enrolled in the OAT (Occluded Artery Trial), which randomized stable patients with an occluded infarct-related artery to PCI or optimal medical treatment alone. Although patients who underwent stress testing had better outcomes, mild-to-moderate ischemia was not associated with any difference in outcomes, and did not predict any advantage for PCI.
Renal failure has been increasingly recognized as an adverse prognostic factor. Hakeem et al. (56) followed 652 patients for 2.15 ± 0.8 years following stress SPECT and found that SPECT findings and renal dysfunction were independent predictors of subsequent cardiac death. Even in the presence of a normal scan, patients with chronic kidney disease had a less benign prognosis (Fig. 7).
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Figure 7 Effect of GFR on Clinical Outcomes
Annual rate of cardiac death according to summed stress score (SSS) by single-photon emission computed tomography and estimated glomerular filtration rate (GFR). There were significant (p < 0.05) differences across strata of SSS and GFR. Reprinted, with permission, from Hakeem et al. (55). n = number of patients in each stratum.
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The accurate prediction of sudden cardiac death remains a clinical challenge. Piccini et al. (57) demonstrated a significant association between summed stress score and subsequent sudden cardiac death in 6,383 patients with CAD followed over a median of 6.1 years. As Albert (58) pointed out in an accompanying editorial, the clinical significance of this finding is uncertain without analysis of the impact of the results on risk stratification. Tamaki et al. (59) reported that cardiac metaiodobenzylguanidine (MIBG) and washout rate and EF were independently significant in predicting sudden cardiac death in 106 outpatients with systolic heart failure, but the study was limited by a small number of events (n = 18) and the absence of beta-blocker therapy.
SPECT and CT.
Prognostic comparisons of SPECT and coronary CTA are of great current interest. van Werkhoven et al. (60) followed 541 patients who underwent both SPECT and coronary CTA for a median of 672 days. Although SPECT and coronary CTA provided independent prognostic information, the study was limited by a relatively small number of hard events (16).
PET.
Ejection fraction (EF) can be easily measured with gated PET. Lertsburapa et al. (61) reported that EF by PET provided prognostic information that was incremental to PET stress perfusion, and suggested that EF should be routinely measured.
Two important studies addressed the limited available data regarding the prognostic value of PET perfusion. Tio et al. (62) followed 344 medically treated patients with ischemic heart disease, for a median of 7 years and reported that myocardial perfusion reserve assessed by dipyridamole-ammonia PET was highly predictive of cardiac death. Dorbala et al. (63) reported similar findings with vasodilator stress rubidium PET on a much larger cohort of 1,432 patients followed for 1.7 ± 0.7 years. They also reported incremental prognostic value for stress-induced EF changes measured in a subset of 985 patients.
CT.
The presence of coronary calcium predicts cardiac events. This year, several studies reported the outcomes of patients with negative or very low coronary calcium scores. Sarwar et al. (64) performed a systematic review of 49 studies of coronary calcium CT exams on 71,595 asymptomatic patients and 3,924 symptomatic patients. Over a mean follow-up period of 50 months, 154 of 29,312 asymptomatic patients with no coronary calcium had cardiovascular events (0.47%), compared with 1,749 of 42,283 asymptomatic patients with coronary calcium (4.14%; p < 0.001). Among symptomatic patients, 17 of 921 patients (1.8%) without calcium had events over the ensuing 42 months, compared with 270 of 3,003 (8.99%) with coronary calcium. The cumulative relative risk ratio for the absence of coronary calcium in asymptomatic patients was 0.15 (95% CI: 0.11 to 0.21; p < 0.001) and in symptomatic patients 0.09 (95% CI: 0.04 to 0.20; p < 0.0001).
Blaha et al. (65) evaluated all-cause mortality in a cohort of 44,052 patients over a 5-year period. In the 5,388 patients with low positive coronary artery calcium (CAC) scores (CAC = 1 to 10), mortality was 1.06%, which was significantly higher than in patients with no coronary calcium (0.52%) and significantly lower than in patients with CAC >10 (3.96%).
There have been limited data on the prognostic value of coronary CTA. Hadamitzky et al. (66) followed 1,256 patients with suspected CAD over a median of 18 months and reported that  50% stenosis in any coronary artery was predictive of severe cardiac events (0.17% risk vs. 0.1% risk; odds ratio: 17.3; 95% CI: 3.6 to 82.5), and added to the Framingham risk score (Fig. 8). The rate of severe cardiac events in the overall study group was only 0.8%.
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Figure 8 Prognostic Value of Coronary CTA
Rate of severe cardiac events according to the presence or absence of obstructive coronary artery disease (CAD) detected by coronary computed tomography angiography (CTA). Reprinted, with permission, from Hadamitzky et al. (66). Pt = patients.
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Motoyama et al. (67) evaluated coronary CTA in 1,059 patients to determine plaque characteristics associated with an unfavorable prognosis (mean follow-up: 27 ± 10 months). Twenty-two percent (10 of 45) of patients with low-attenuation coronary plaques and associated positive remodeling developed an ACS compared with 0.49% (4 of 820) of patients with atherosclerotic plaques demonstrating neither of these features (hazard ratio: 22.8; p < 0.001). None of the 167 patients with normal coronary arteries developed ACS.
Carrigan et al. (68) followed 277 patients for 2 years (mean 2.3 ± 0.8 years). The presence of proximal coronary plaque (at least 30% diameter reduction) and total plaque score each added significantly to clinical variables in predicting major cardiac events.
Van Lingen et al. (69) followed 178 patients with no significant coronary stenosis (<50%) by CTA for 1 year (range 51 to 1,113 days) and found no unstable angina, MI, or death, although 2 patients did have coronary revascularization.
MRI.
As MRI stress testing has become more established, there is a growing body of literature supporting the prognostic importance of these examinations (Table 3, Fig. 9) (70–73).
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Figure 9 Prognostic Value of Dobutamine MRI
Patients with stress-induced wall motion abnormalities (an increase in wall motion size index [WMSI]) at dobutamine magnetic resonance imaging (MRI) were more likely to have myocardial infarction or cardiac death after 5 years of follow-up. Modified from Dall'Armellina et al. (70).
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Delayed enhancement alone has prognostic significance. Kwon et al. (74) followed 349 patients with ischemic cardiomyopathy for 2.6 ± 1.2 years; the amount of delayed enhanced myocardium was associated with an increased risk of all-cause mortality or cardiac transplantation, independent of age or LV ejection fraction.
MRI can help guide cardiac resynchronization therapy (CRT). Bilchick et al. (75) performed MRI on 20 patients prior to CRT; the combination of an MRI dyssynchrony index with MRI infarct quantification produced 100% sensitivity and 85% specificity for predicting CRT response.
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Structure and Function
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CT.
ECG-gated CT is increasingly being used for morphologic assessment of extracoronary cardiac structures; several studies established normal reference values. Budoff et al. (76) used electron beam CT and 64-row multidetector CT to measure LV mass in 2,238 patients without a known cause of left ventricular hypertrophy (LVH) and found low variability of the CT measurements by both techniques. They found that application of existing echocardiographic criteria for LVH mass would misclassify a significant number of patients, and recommended new CT criteria for LVH.
Lin et al. (77) used CT in 103 patients to estimate normal ranges for LV, left atrial, right ventricular, and right atrial size, function, and mass.
Halpern et al. (78) compared CT planimetry of aortic valve area with echocardiography in 41 patients and found good correlation (r = 0.88) when direct measurement of LV outflow tract area was used in the continuity equation in place of estimates based on diameter.
The use of CT for detection of atrial thrombus remains an active topic for investigation. Feuchtner et al. (79) compared ECG-gated CTA with transesophageal echocardiogram (TEE) in 64 patients and found excellent sensitivity (100%) and decent specificity (73%) for left atrial thrombus. Hur et al. (80) evaluated a 2-phase CT angiographic technique in 55 stroke patients and found excellent specificity (98%) with preserved sensitivity (100%) for the detection of left atrial appendage thrombus as compared with TEE. Martinez et al. (81) performed CT and TEE on 402 patients prior to ablation of atrial fibrillation. The absence of a filling defect on CT had a 100% negative predictive value for LA thrombus.
MRI.
Plaque
MRI plaque characterization of the coronary arteries is technically challenging due to their small size and rapid motion. However, plaque characterization is easier in other vessels, such as the carotid artery. Boussel et al. (82) reported a multicenter trial in which 108 patients with 50% carotid artery stenoses were imaged at baseline and 1 year later. Patients not taking a statin had an increase in wall volume of 7.87 ± 13.58%, which was significantly greater than the increase in wall volume of 1.14 ± 9.9% in patients taking a statin (p = 0.029).
Miao et al. (83) described coronary wall remodeling in 179 asymptomatic patients enrolled in the MESA (Multi-Ethnic Study of Atherosclerosis). They imaged the proximal coronary artery in cross-section and compared the total coronary wall thickness with the outer contour area and the luminal area, before and after adjustment for body mass index and LV mass. The predominant change in vessel size was due to a larger increase in outer wall area than in the luminal area, which the authors interpreted as positive remodeling (Figs. 10
and 11).
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Figure 10 MRI Imaging of Coronary Artery Wall
Magnetic resonance imaging (MRI) cross-section through the left main coronary artery (arrow, inset) shows eccentrically thickened arterial walls. Reprinted, with permission, from Miao et al. (83).
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Figure 11 Relationship of Coronary Lumen and Outer Contour
Comparison of coronary lumen area and coronary outer contour area to coronary wall thickness in women. The outer contour and the lumen area were both positively correlated with the mean coronary wall thickness (r = 0.62 and r = 0.09, p < 0.001 and p < 0.05, respectively), but the slope of the outer contour area increase was significantly greater than that of the lumen area increase (p < 0.0001). Reprinted, with permission, from Miao et al. (83).
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Morphology
Several studies used MRI parameters to predict outcome in nonischemic conditions. Bluemke et al. (84) showed the prognostic value of LV mass by MRI in 5,098 asymptomatic volunteers followed for 4 years as part of the MESA study. LV mass and LV mass divided by LV volume were both associated with an increased risk of heart failure after adjustment for a variety of risk factors.
McGann et al. (85) used MRI to predict response to radiofrequency pulmonary vein isolation for treatment of atrial fibrillation in 46 patients. Patients who responded to radiofrequency ablation had more left atrial wall delayed enhancement than patients who did not respond (19 ± 7% vs. 12 ± 6%, p = 0.004).
Adabag et al. (86) showed that delayed enhancement had prognostic value in 177 patients with hypertrophic cardiomyopathy. Delayed enhancement was associated with a greater likelihood of ventricular tachyarrhythmias.
Zagrosek et al. (87) described the patterns of reversible and irreversible injury in 36 patients with myocarditis who were imaged within the first week of presentation and again at 18 ± 10 months. The acute phase was characterized by increased edema (increased signal on T2-weighted images), and irreversible injury was characterized by delayed enhancement.
In contrast, Schietinger et al. (88) found delayed enhancement in 19 of 24 (79%) of chronic hemodialysis patients. Thirteen of the 19 (68%) patients with delayed enhancement had a pattern suggestive of fibrosis, but not MI.
Steen et al. (89) found that 15 of 41 (37%) transplant patients had delayed enhancement suggestive of infarction. Among patients with only mild transplant coronary disease by catheter angiography, 5 of 22 (23%) had delayed enhancement suggestive of infarction.
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Health Care Policy
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SPECT.
Levin et al. (90) used the nationwide Medicare administrative database to examine the trends in myocardial perfusion imaging between 1998 and 2006. The rate of private office utilization per 1,000 Medicare beneficiaries increased by 215% for cardiologists in office settings, compared with only 32% among radiologists in hospital settings. The 2006 utilization rate for cardiologists in office settings was 47.3 per 1,000 Medicare beneficiaries, more than 4-fold higher than the rate of 10.7 for stress echocardiograms.
Appropriateness criteria may help to moderate these growth rates. McCully et al. (91) compared the stress SPECT criteria and the stress echo criteria in 298 patients who underwent stress echocardiography. They reported considerable differences in patient classification according to the 2 different sets of criteria, suggesting the need for future refinements. Hendel et al. (92) published the revised American College of Cardiology Foundation (along with multiple other organizations) appropriateness criteria for SPECT imaging, which clarified many of the issues that had been raised in studies of the original criteria published in 2005. Unfortunately, Bautista et al. (93) surveyed 126 physicians in their institution and found that American College of Radiology appropriateness criteria were rarely used, and ranked well behind Google as a resource. Mehta et al. (94) applied the 2005 appropriateness criteria to their academic practice and reported that 13% of their SPECT studies were inappropriate. Khandaker et al. (95) reported that stress SPECT studies could effectively risk stratify asymptomatic patients at moderate CAD risk by Framingham criteria, an indication that was considered to be of uncertain appropriateness in the 2005 criteria.
SPECT and CT.
Will coronary CTA save money? Using a large administrative claims database, Min et al. (96) reported lower total healthcare and CAD expenditures for patients without known CAD who were evaluated with coronary CTA compared with those who underwent SPECT, without any differences in outcome. Unfortunately, important clinical information, such as pre-test symptoms, smoking status, and cholesterol levels, were not available in the database.
In a second study, Min et al. (97) followed 8,235 patients without known CAD for 1 year after either coronary CTA or SPECT to determine subsequent events and medical costs. Overall event rates were low (0.4%). Although total costs were lower for CT patients (by $1,075 per patient), the incidence of revascularization was higher in the SPECT group, suggesting higher pre-test likelihood of disease in these patients.
CT.
Menon et al. (98) evaluated the utility of coronary CTA to prevent invasive coronary angiography after suspected false positive stress testing. Only 57 of 385 patients who had multidetector CTA after stress testing were referred on to cardiac catheterization (14.8%); CTA compared well with invasive angiography (positive predictive value = 94%, negative predictive value = 100%). Although 11% of the CTAs were false positive (6/54), the use of CT as a gatekeeper resulted in a theoretical 4-fold cost savings.
Using a Monte Carlo simulation model to evaluate coronary CTA for triage of "low-risk" chest pain patients in the emergency department, Ladapo et al. (99) demonstrated theoretical cost savings in female patients and relatively cost-effective care in male patients ($6,400 per quality-adjusted life-year) as compared with standard of care.
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Conclusions
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As we have said previously, we hope that this review will encourage the reader to examine some of these papers in more detail and, ultimately, to more carefully apply the correct imaging modality to each clinical problem.
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Footnotes
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Dr. Gibbons has received research grant support from King Pharmaceuticals and served as a consultant to Molecular Insight Pharmaceuticals. Dr. Araoz has served as a consultant for Medtronic.
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References
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