Cardiovascular Magnetic Resonance Stress Testing
Appreciation of LV myocardial ischemia has traditionally depended on identifying abnormalities of LV myocardial perfusion, wall motion, metabolism, or epicardial coronary artery blood flow after experiencing some form of stress. CMR is unique in that with a single imaging modality one can identify abnormalities of LV myocardial perfusion or wall motion in a single test with a relatively high spatial resolution and without administration of any form of ionizing radiation (Fig. 16–11). Based on multimodality appropriate use criteria, stress CMR is considered appropriate for patients with high pretest probability for coronary artery disease (CAD) or intermediate pretest probability of CAD with an uninterpretable ECG or inability to exercise.38 It is also appropriate for patients with an abnormal ECG who are intermediate-to-high risk as well as those with an abnormal or uncertain exercise ECG or those with obstructive CAD of uncertain significance noted on computed tomography (CT) or invasive coronary angiography.
Mechanisms by which cardiovascular magnetic resonance (CMR) may appreciate functional evidence of epicardial coronary arterial stenoses. LV, left ventricular.
Imaging Suite and Environment
It is important to recognize that appropriate environmental conditions and safety procedures are required when seeking to perform CMR stress testing. Similar to stress testing environments used with other modalities, staff familiar with CV stress testing, including nursing personnel and physicians, should be present during and immediately after testing.39,40 In regard to safety, medication carts and defibrillators should be secured outside of, but in close proximity to, the CMR scanning room, and if defibrillation during testing should be required, patients should be removed from the CMR room to deliver cardioversions. It is also important to note that specialized MRI-compatible equipment for assessing blood pressure, heart rate, oxygen saturation, and respiratory rate should be present in the MRI scanning room. Because the magnetic field alters the appearance of ST segments and T waves on the ECG once the patient enters the scanner, ECG tracings are used to monitor patients' rhythm and not to detect ST-segment changes associated with inducible ischemia. As such, many stress CMR facilities utilize near real-time image review to appreciate inducible ischemia (Fig. 16–12). As shown in Fig. 16–13, prior to CMR stress testing, a resting 12-lead ECG, intravenous access, pulse oximetry, and brachial blood pressure cuff are applied outside of the magnet room.41
A photograph of a stress cardiovascular magnetic resonance (CMR) testing suite. The individual on the left (technologist) performs the scans, and the individual on the right (physician) reviews the stress image results in near real time. Through the window, the patient is seen in the CMR scanner with hemodynamic monitoring occurring during stress. Reproduced with permission from Chotenimitkhun R, Hundley WG: Pharmacological stress cardiovascular magnetic resonance. Postgrad Med. 2011 May;123(3):162-170.
Images highlighting the preparation/recovery area (left) as well as the scanning facility (right). Note that by utilizing a preparation and recovery area, patient throughput in a cardiovascular magnetic resonance center is enhanced, because the scanning facility is not used for time-consuming, non–scan-related tasks such as insertion of intravenous catheters or placement of special monitoring equipment.
In one of the largest studies of more than 1000 individuals undergoing dobutamine stress CMR, potential side effects were noted to occur in 6.4% of individuals (vasodilator stress CMR has an even better safety profile).42 The side effects included sustained ventricular tachycardia (0.1%); nonsustained ventricular tachycardia (0.4%); paroxysmal atrial fibrillation (AF) (1.6%); transient second-degree atrioventricular block (0.2%); marked changes in systolic blood pressure, including elevations to greater than 240/120 mm Hg (0.5%); and substantial decreases of > 40 mm Hg (0.5%). Accordingly, personnel familiar with managing these conditions should be present.
Major events during CMR stress testing are usually associated with continued infusions of pharmacologic stress agents in the setting of concurrent myocardial ischemia. As such, near simultaneous viewing of images is recommended and a high level of attention is suggested so that termination of the stress procedure can occur once evidence of ischemia is present (see Fig. 16–12).
For dobutamine stress testing, baseline images are acquired in three standard long-axis and short-axis views at rest (Fig. 16–14). Dobutamine (in increasing doses up to 50 μg/kg/min) and atropine are then infused to achieve a heart rate response that is 85% of the maximum predicted heart rate response for age.43 Optionally at intermediate stages, repeat wall motion images may be obtained. At peak stress or at the first sign of chest pressure consistent with angina, repeat wall motion and myocardial stress perfusion images are acquired (see Fig. 16–14).39,40,41,42,43 The pharmacologic stress agents are then discontinued, and a recovery series of images is obtained. To interpret the test, the left ventricle is divided into 17 segments according to the American Heart Association and American College of Cardiology.44 Throughout testing, a four-point scoring system (1 = normal, 2 = hypokinetic, 3 = akinetic, 4 = dyskinetic) is used to assess wall motion within each segment. Myocardial ischemia is identified when a deterioration of ≥ 1 in a segment score occurs during the stress test (Fig. 16–15).
A. Dobutamine infusion protocol for cardiovascular stress testing. As shown, three apical and three short-axis views are acquired at baseline (B) over a 3-minute period. Also, heart rate (HR) and blood pressure (BP) are collected. Next, dobutamine is infused at 10 μg/kg/min, and the three apical and three short-axis views are repeated. At peak stress, a combination of dobutamine and atropine (At) are infused to achieve 85% of the maximum predicted HR response for age, and wall motion acquisitions are repeated. At this time, gadolinium first-pass perfusion images may be acquired. On completion of the peak stress image acquisitions, recovery (A) images are obtained prior to patient discharge. Also, if contrast was administered, late gadolinium-enhanced (LGE) images may be acquired. The total scan time for an individual with a negative stress test averages 25 minutes using this protocol. Ox, oxygen saturation; Res, respiratory rate. B. Cine magnetic resonance images of the left ventricle are displayed in three short-axis (upper row) and three long-axis (lower row) views. The left ventricular myocardium is divided into 17 segments as identified: 1 = basal anterior; 2 = basal anteroseptum; 3 = basal inferoseptum; 4 = basal inferior; 5 = basal inferolateral; 6 = basal anterolateral; 7 = midanterior; 8 = midanteroseptum; 9 = midinferoseptum; 10 = midinferior; 11 = midinferolateral; 12 = midanterolateral; 13 = apical anterior; 14 = apical septum; 15 = apical inferior; 16 = apical lateral; and 17 = apical cap. SAX, short axis. Reproduced with permission from Rerkpattanapipat P, Hundley WG: Dobutamine stress magnetic resonance imaging. Echocardiography. 2007 Mar;24(3):309-315.
Positive dobutamine cardiac magnetic resonance (DCMR). DCMR cine images (short-axis and two-chamber view) of a patient with chest pain and suspected coronary artery disease (top). At rest and under increasing dobutamine, there is normal regional function. However, at maximum stress, an inferolateral wall motion abnormality is elicited. X-ray coronary angiography images demonstrating single-vessel left circumflex coronary artery disease (bottom, black arrows). Reproduced with permission from Paetsch I, Jahnke C, Fleck E, et al: Current clinical applications of stress wall motion analysis with cardiac magnetic resonance imaging. Eur J Echocardiogr. 2005 Oct;6(5):317-326.
As shown in Table 16–2, the sensitivity and specificity of dobutamine stress CMR for detecting greater than 50% coronary arterial stenoses with wall motion analyses alone range from 78% to 96%.45 It is important to recognize, however, that there are several situations in which dobutamine wall motion analyses alone may underappreciate the presence of inducible ischemia and functionally important CAD. To address these outstanding issues, several investigators have advocated for the incorporation of first-pass contrast-enhanced stress perfusion at peak heart rate response during intravenous dobutamine, and the acquisition of LGE images in the recovery phase of dobutamine and atropine administration (see Fig. 16–14). In 1493 patients referred for dobutamine stress with suspected or known CAD, the simultaneous identification of LV wall motion and myocardial perfusion abnormalities was associated with an increase in the hazard ratio for future CV events.46 The results of myocardial perfusion stress testing were most evident in those individuals with resting LV wall motion abnormalities or underlying left ventricular hypertrophy (LVH) (P =.02–.09).
TABLE 16–2.Utility of Dobutamine Wall Motion Stress Cardiovascular Magnetic Resonance for Identifying ≥ 50% Coronary Arterial Luminal Narrowing ||Download (.pdf) TABLE 16–2. Utility of Dobutamine Wall Motion Stress Cardiovascular Magnetic Resonance for Identifying ≥ 50% Coronary Arterial Luminal Narrowing
|Author (Reference Number) ||Patients (n) ||Men (%) ||Mean Age (years) ||Dobutamine Dose (μg/kg/min) ||Sensitivity (%) ||Specificity (%) |
|Gebker et al (47) ||455 ||65 ||64 ||40 + atropine ||91 ||70 |
|Hundley et al (39) ||163 ||56 ||NS ||40 + atropine ||83 ||83 |
|Korosoglou et al (258) ||80 ||73 ||62 ||40 + atropine ||83 ||91 |
|Kuijpers et al (42) ||194 ||67 ||62 ||40 ||96 ||95 |
|Nagel et al (40) ||208 ||71 ||60 ||40 + atropine ||86 ||86 |
|Paetsch et al (259) ||79 ||66 ||61 ||40 + atropine ||89 ||80 |
|Paetsch et al (260) ||150 ||83 ||61 ||40 + atropine ||78 ||88 |
|Pennell et al (261) ||25 ||74 ||52 ||20 ||91 ||100 |
|Schalla et al (262) ||22 ||80 ||60 ||40 + atropine ||81 ||83 |
|van Rugge et al (263) ||45 ||82 ||61 ||20 ||81 ||100 |
|van Rugge et al (264) ||39 ||86 ||60 ||20 ||91 ||80 |
|Wahl et al (265) ||160 ||- ||59 ||40 + atropine ||89 ||84 |
These situations include those individuals with resting LV segmental wall motion abnormalities, the presence of prior MI and scar, those with LVH or concentric remodeling, and, finally, those individuals who are older and exhibit a hyperdynamic response with a decline in systolic blood pressure during testing.47
In 278 individuals48 aged 69 ± 8 years with preexisting or known risk factors for CAD who underwent simultaneous assessment of LV myocardial perfusion and wall motion after peak dobutamine infusion, 60% of individuals with perfusion defects indicative of myocardial ischemia exhibited no inducible wall motion abnormalities. Among these participants, myocardial oxygen demand was lower in those who had both LV wall motion and perfusion abnormalities suggestive of ischemia (P =.03). Factors associated with the presence of perfusion defects without an inducible wall motion abnormality included a reduced LV end-diastolic volume index (LV preload) or increased concentric LV remodeling. The results of these studies demonstrate the limitations of LV wall motion assessments alone when evaluating patients referred for any form of dobutamine stress examinations (CMR, echocardiography, radioisotope imaging) and point out the ability of simultaneous LV wall motion and perfusion assessments in these same situations.
Contractile Reserve and Viability
Although LGE techniques are widely used for identifying myocardial scar and thus infer viability, dobutamine stress CMR measures of LV myocardial contractile reserve remain important for assessing myocardial segments that have the potential to recover systolic function after successful epicardial coronary arterial revascularization.49,50 Similar to the protocol utilized for myocardial ischemia, in patients undergoing dobutamine viability studies, resting images are obtained prior to initiation of stress. After baseline imaging, low-dose dobutamine infusions in the range of 7.5 to 10 μg/kg/min are administered and repeat assessments of myocardial contractility are obtained. The first study51 to publish comparisons of dobutamine stress CMR and 8F-fluorodeoxyglucose positron emission tomography (PET) demonstrated that dobutamine-induced wall thickening was superior to resting LV end-diastolic wall thickness alone for predicting viable myocardium. In fact, dobutamine stress CMR had similar diagnostic accuracy relative to 8F-fluorodeoxyglucose PET scanning.
A particular advantage of low-dose dobutamine infusions for assessing myocardial viability is that they can be administered to patients with reactive airways disease as well as those with renal dysfunction in whom the use of gadolinium may be contraindicated. In addition, there is some evidence that low-dose dobutamine stress CMR assessments of improvements in regional wall motion or radial thickening may be superior to the assessments of LGE, particularly in individuals who have intermediate presence of LGE (Fig. 16–16; see also section on remote myocardial infarction).50
Transmurality of late gadolinium enhancement (LGE): subgroup analysis. Bars refer to the prevalence of recovery and sensitivity, specificity, and percentage of correct predictions by dobutamine cardiac magnetic resonance (DCMR) and are subgrouped with respect to LGE (cutoff: 25%). The specificity of DCMR remains high irrespective of the extent of LGE. The test retains high sensitivity in 25% to 49% LGE. Reproduced with permission from Wellnhofer E, Olariu A, Klein C et al: Magnetic Resonance Low-Dose Dobutamine Test Is Superior to Scar Quantification for the Prediction of Functional Recovery. Circulation. 2004 May 11;109(18):2172-2174.
CMR perfusion imaging in general is accomplished after the administration of contrast agents that help to demonstrate discrepancies in LV myocardial perfusion between adjacent myocardial segments as well as absolute perfusion within a particular segment.52 For the most part, GBCAs are utilized because of their ability to accentuate T1 relaxivity in perfused myocardium as well as a relatively favorable safety profile for administration in those without severe chronic kidney disease.53
With CMR, myocardial perfusion may be assessed qualitatively (visual inspection), semiquantitatively, or by fully quantitative methods that assess the absolute perfusion of the agent.54 Quantitative perfusion methods have been found very accurate and to vary inversely with the degree of coronary stenosis by quantitative coronary angiography. Importantly, both quantitative as well as qualitative perfusion assessments by CMR have demonstrated very high correlations with fractional flow reserve measures using cutoff values of < 0.75.55 Overall, those studies using qualitative assessments may require larger amounts of gadolinium contrast in the 0.1 mmol/kg range to optimize visualization, whereas quantitative analysis may be achieved with much lower doses, such as 0.05 mmol/kg. Although quantitative and qualitative analyses have similar accuracy on a per-patient basis, quantitative analysis of perfusion reserve identifies the extent of myocardial ischemia more accurately.56
Although intravenous adenosine or dipyridamole has traditionally been administered to accomplish vasodilator stress, regadenoson has been utilized in the CMR environment as well. This agent is beneficial for the study of individuals with obstructive or reactive airways disease in that regadenoson will enhance endothelial independent vasodilation of the coronary microcirculation but not precipitate bronchial constriction associated with lung disease.57
The stress perfusion protocol includes a stress perfusion assessment, followed by evaluation of LV wall motion, rest perfusion, and LGE identification of myocardial injury/fibrosis. Utilizing this methodology, the sensitivities and specificities for identifying flow-limiting coronary arterial stenoses when compared to contrast coronary angiography have both exceeded 90%.58 The high spatial resolution of this technology enables identification of subendocardial infarcts that can be distinguished from small areas of subendocardial hypoperfusion related to reduced myocardial microcirculatory blood flow (Fig. 16–17) resulting from flow-limiting epicardial coronary arterial stenoses. In addition, this particular technique is useful for identifying inducible ischemia in those individuals with preexisting concentric LVH or remodeling, reduced LVEF, or female gender (when body habitus can impede acquisition with other methodologies).
Interpretation algorithm for incorporating delayed enhancement magnetic resonance imaging (DE-MRI) with stress and rest perfusion MRI for the detection of coronary disease. A. Schema of the interpretation algorithm. (1) Positive DE-MRI study: Hyperenhanced myocardium consistent with a prior myocardial infarction (MI) is detected. Does not include isolated midwall or epicardial hyperenhancement, which can occur in nonischemic disorders. (2) Standard negative stress study: No evidence of prior MI or inducible perfusion defects. (3) Standard positive stress study: No evidence of prior MI, but perfusion defects are present with adenosine that are absent or reduced at rest. (4) Artifactual perfusion defect: Matched stress and rest perfusion defects without evidence of prior MI on DE-MRI. B. Patient examples. (top row) Patient with a positive DE-MRI study demonstrating an infarct in the inferolateral wall (red arrow) although perfusion-MRI is negative. The interpretation algorithm (step 1) classified this patient as positive for coronary artery disease (CAD). Coronary angiography verified disease in a left circumflex (LCX) marginal artery. Cine MRI demonstrated normal contractility. (middle row) Patient with a negative DE-MRI study but with a prominent reversible defect in the anteroseptal wall on perfusion-MRI (red arrow). The interpretation algorithm (step 3) classified this patient as positive for CAD. Coronary angiography demonstrated a proximal 95% left anterior descending (LAD) coronary artery stenosis. (bottom row) Patient with a matched stress-rest perfusion defect (blue arrows) but without evidence of prior MI on DE-MRI. The interpretation algorithm (step 4) classified the perfusion defects as artifactual. Coronary angiography demonstrated normal coronary arteries. Reproduced with permission from Klem I, Heitner JF, Shah DJ, et al: Improved detection of coronary artery disease by stress perfusion cardiovascular magnetic resonance with the use of delayed enhancement infarction imaging. J Am Coll Cardiol. 2006 Apr 18;47(8):1630-1638.
Across several meta-analyses, the overall sensitivity and specificity of CMR vasodilator perfusion tests for identifying flow-limiting coronary artery stenoses were 91% and 81%, respectively. In addition, in a relatively large meta-analysis,59 reporting on 4721 vessels in 2048 patients, CMR vasodilator stress performed similarly to CT and PET and better than single-photon emission computed tomography (SPECT) or echocardiography using pooled sensitivity and specificity analyses for identifying functionally important CAD (Table 16–3). When compared with fractional flow reserve measures, CMR has been shown in multicenter initiatives to compare favorably, and perhaps superiorly, to existing radioisotope and radionuclide techniques.60 Several comparative study results have suggested that CMR perfusion imaging could realistically be used as an alternative (with superior results) to SPECT imaging. This was most convincingly demonstrated in the recent single-center Clinical Evaluation of Magnetic Resonance Imaging in Coronary Heart Disease (CE-MARC) study that directly compared CMR stress perfusion and LGE with SPECT.61 In this study, CMR was found to have higher sensitivity and similar specificity to SPECT, using angiography stenosis severity as a study end point (Fig. 16–18). In addition, abnormal CMR stress perfusion abnormalities correlate with fractional flow reserve assessments obtained invasively.55
Results of the clinical evaluation of magnetic resonance imaging in coronary heart disease (CE-MARC) study. Stress magnetic resonance perfusion had higher diagnostic sensitivities for both single and multivessel coronary stenosis than single-photon emission computed tomography (SPECT). CMR, cardiac magnetic resonance; LAD, left anterior descending coronary artery; LCx, left circumflex artery; LMS, left main stem; RCA, right anterior descending coronary artery. Reproduced with permission from Daly C1, Kwong RY: Cardiac MRI for myocardial ischemia. Methodist Debakey Cardiovasc J. 2013 Jul-Sep;9(3):123-131.
TABLE 16–3.Outcome Summary at Patient Level ||Download (.pdf) TABLE 16–3. Outcome Summary at Patient Level
|Index Test ||No. of Patients ||TP ||FP ||FN ||TN ||Sensitivity ||Specificity ||PLR ||NLR ||DOR ||AUC ||Q*-Statistic |
|SPECT ||533 ||162 ||67 ||58 ||246 ||0.74 (0.67–0.79) ||0.79 (0.74–0.83) ||3.13 (2.09–4.70) ||0.39 (0.27–0.55) ||9.63 (4.57–20.31) ||0.82 (0.73–0.91) ||0.75 (0.68–0.83) |
|ECHO ||177 ||46 ||18 ||21 ||92 ||0.69 (0.56–0.79) ||0.84 (0.75–0.90) ||3.68 (1.89–7.15) ||0.42 (0.30–0.59) ||12.04 (5.25–27.65) ||0.83 (0.74–0.93) ||0.76 (0.68–0.85) |
|MRI ||798 ||355 ||52 ||43 ||348 ||0.89 (0.86–0.92) ||0.87 (0.83–0.90) ||6.29 (4.88–8.12) ||0.14 (0.10–0.18) ||50.94 (32.45–79.97) ||0.94 (0.92–0.96) ||0.88 (0.85–0.90) |
|PET ||224 ||73 ||18 ||14 ||119 ||0.84 (0.75–0.91) ||0.87 (0.80–0.92) ||6.53 (2.83–15.06) ||0.14 (0.02–0.87) ||47.26 (4.17–536.29) ||0.93 NA ||0.87 NA |
|CT ||316 ||143 ||30 ||20 ||123 ||0.88 (0.82–0.92) ||0.80 (0.73–0.86) ||3.79 (1.94–7.40) ||0.12 (0.04–0.33) ||43.36 (20.26–92.78) ||0.93 (0.89–0.97) ||0.87 (0.82–0.92) |
Beyond the identification of flow-limiting coronary stenoses or inducible ischemia, both CMR myocardial perfusion as well as CMR dobutamine wall motion stress are useful to determine cardiac prognosis.62 In populations with chest pain presenting to the emergency department, CMR perfusion exhibits a sensitivity of 100% and specificity of 93% for predicting subsequent death from MI or detection of coronary stenosis after one year of follow-up.63 In another study,64 both adenosine myocardial perfusion as well as dobutamine CMR wall motion were evaluated in 513 patients subsequently followed for up to 3 years. Stress CMR using myocardial perfusion or wall motion analyses contributed to the incremental value over traditional risk factors for identifying those with an adverse cardiac prognosis. Normal perfusion studies were associated with an event rate of 0.7% at 2 years, whereas an abnormal study exhibited an event rate of 12.2% over the same time period. In a multivariable analysis including other risk factors for cardiac events, detection of perfusion abnormalities was associated with a 10-fold risk of future hard events. Similar results were found for dobutamine wall motion assessments.
A particular advantage for utilizing stress CMR for assessing myocardial perfusion or LV wall motion relates to the prognostic utility in women.65,66 As shown in Fig. 16–19, stress CMR exhibits very high spatial resolution and fewer artifacts for imaging women relative to radioisotope techniques and, importantly, CMR stress does not involve ionizing radiation exposure to breast tissue.
Importance of spatial resolution in stress perfusion imaging. Patient has an inducible perfusion defect limited to the subendocardial portion of the septal wall (black arrow) caused by an ostial stenosis (white arrow) of a septal branch of the left anterior descending coronary artery.
In a meta-analysis totaling 14 studies involving 12,178 individuals,62 the negative predictive value for nonfatal MI and cardiac death of a normal CMR was 98.1% (with a 95% confidence interval of 97.3 to 98.8) during a main follow-up of 25.3 months. The corresponding annualized event rate after a negative test was 1.03%. These results demonstrate that CMR exhibits a relatively high negative predictive value for adverse cardiac events, and the absence of inducible perfusion defects or wall motion abnormalities demonstrate a similar ability to identify low risk patients with known or suspected CAD.62
Health Care Expenditures and Utilization
Although clear algorithms for diagnosis and treatment of patients with chest pain at varying levels of risk for acute coronary syndrome (ACS) exist, there are less well-delineated criteria for those individuals presenting with chest pain at intermediate risk for ACS. An important series of studies from Miller and colleagues67,68,69 has demonstrated the utility of stress CMR in chest pain observation units associated with emergency departments. Three recent studies involving more than 300 participants randomized to usual cardiac care versus a stress CMR implemented through chest pain observation units examined those presenting with intermediate-risk chest pain (preexisting CAD and MI, ECGs with T-wave inversions without ST-segment depression exceeding 3 mm or ST-segment elevation exceeding 1 mm). Participants managed through the CMR-guided pathways experienced on average a reduction in the cost of the initial visit of $588 and reduction of $1641 over the ensuing year (Fig. 16–20).67,68,69 When examined further, the decreased utilization and costs associated with managing the patients using CMR results was related to fewer return visits to the emergency department, cardiac catheterizations, and percutaneous coronary artery revascularization procedures. Overall, patients experienced no difference in the 30 days or 1-year occurrence of MI or cardiac death. These important results highlight the potential benefits of using CMR stress perfusion for identifying those individuals presenting to the emergency department with chest pain at intermediate risk for ACS and in need of hospitalization, as opposed to those who could be safely discharged to home.
Cost accumulation by month following discharge among study groups, excluding the index hospital visit cost. Mean cumulative cost by study group after hospital discharge (y axis) is displayed by month of follow-up (x axis). Mean cumulative cost for a month is calculated as the sum of the costs across all patients up to and including that month divided by the number of patients. Observation unit cardiac magnetic resonance (OUCMR) participants had lower cost of care in the year after discharge from the index hospital visit (P = .012). Reduced cost was the result of fewer cardiac-related emergency department visits and cardiac-related hospitalizations, suggesting that an OUCMR strategy impacts care utilization after discharge. Reproduced with permission from Miller CD, Hwang W, Case D, et al: Stress CMR imaging observation unit in the emergency department reduces 1-year medical care costs in patients with acute chest pain: a randomized study for comparison with inpatient care. JACC Cardiovasc Imaging. 2011 Aug;4(8):862-870.
Myocardial Tissue Characterization
Today, perhaps the most widely used imaging method for identifying myocardial injury and fibrosis associated with MI is through CMR-based assessments of LGE.70 LGE has several important uses in the setting of patients with suspected CAD. These include identification of the extent of acute and remote MI, prediction of recovery of myocardial contractility after successful coronary artery revascularization in chronic ischemic heart disease, characterization of prognosis, visualization of cardiac thrombus or microvascular obstruction and, when combined with T2 imaging methods, localization of the area of myocardial salvage.
Acute Myocardial Infarction
Triphenyltetrazolium chloride (TTC) histopathologic staining has been utilized to document the accuracy of the spatial extent and localization of LGE as it relates to infarcted myocardium.71 In canine models, there have been high correlations between LGE and TTC-stained measures of infarcted myocardial segments (Fig. 16–21). The relatively high spatial resolution of LGE images enhances its sensitivity for detecting MI. CMR may be used to identify micro infarcts because of relatively small epicardial coronary artery branch occlusions or embolization of distal vessels related to percutaneous coronary artery revascularization procedures.72 CMR has been shown to be more sensitive than both SPECT and PET imaging for detecting small infarcts.73 In a large multicenter clinical trial of 282 patients, the sensitivity for detecting acute MI was 99%. Transmural extent of LGE can additionally predict the likelihood of functional recovery of stunned myocardium because there is an inverse relationship between transmurality and recovery of function.74
Comparison of ex-vivo, high-resolution, delayed enhancement magnetic resonance images (MRI) with acute myocardial necrosis defined histologically by triphenyltetrazolium chloride (TTC) staining. Note that the size and shape of the infarcted region (yellowish-white region) defined histologically by TTC staining is nearly exactly matched by the size and shape of the hyperenhanced (bright) region on the delayed enhancement image. Modified with permission from Kim RJ, Fieno DS, Parrish TB, et al. Relationship of MRI delayed contrast enhancement to irreversible injury, infarct age, and contractile function. Circulation. 1999 Nov 9;100(19):1992-2002.
Remote Myocardial Infarction
In patients evaluated chronically (months to years) after MI, the assessment of transmural extent of infarction has also been shown to identify the likelihood of functional recovery of systolic thickening after percutaneous coronary artery revascularization procedures.75 For individuals with no LGE, recovery of function of resting segments with akinesis can approach 80%. Conversely, in individuals with greater than 50% transmural extent of infarction, the likelihood of recovery of systolic thickening after coronary artery revascularization falls below 10%.
One potential difficulty in using this method to assess potential for recovery of systolic thickening occurs when the transmural extent of infarction ranges between 1% and 50%. In these situations, there is approximately a 40% to 60% chance of recovery of systolic thickening. As shown in studies by Wellenhoeffer and colleagues, the ability to identify those segments with a potential for systolic thickening after revascularization improves to nearly 90% through the identification of contractile reserve with low dose intravenous dobutamine (see Fig. 16–16).50
In the setting of acute MI, the coronary artery microcirculation can be damaged to an extent such that no gadolinium may be temporarily delivered to specific areas within an infarct zone.76,77 These areas have been shown histopathologically to be associated with microvascular obstruction caused by plugging of the small arterioles with thrombotic debris.76,77 The characteristic image finding (Fig. 16–22) indicates a very dark central core nested within a relatively bright LGE region of myocardium consistent with acute/subacute necrosis. Often on the cine wall motion images, these areas display marked hypokinesis or akinesis. Postcontrast cine imaging can also be useful to differentiate microvascular obstruction from thrombus (see Cardiac Masses, below).
The no reflow phenomenon visualized by delayed enhancement magnetic resonance imaging. Labels refer to time after administration of gadolinium contrast. The subendocardial black zone surrounded by hyperenhancement corresponds to the region of no reflow (white arrows). This region can be distinguished from normal myocardium because it is encompassed in three-dimensional space by hyperenhanced myocardium or the left ventricular cavity and by the fact that it slowly becomes hyperenhanced over time. Reproduced with permission from Higgins CB, Roos Ad: Cardiovascular MRI & MRA. Philadelphia: Lippincott Williams & Wilkins; 2003.
It is important to recognize that the presence of microvascular obstruction is associated with an adverse cardiac prognosis and very little opportunity for recovery of systolic thickening longitudinally over time.78 In addition, the presence of microvascular obstruction has also been associated with adverse LV remodeling and worse patient outcomes.78,79
Myocardial Area at Risk and Salvageable Myocardium
In patients presenting with acute chest pain syndromes, it is important to recognize that edema imaging utilizing either T2-weighted or T2 mapping sequences may be combined with LGE techniques to identify the area at risk and salvageable myocardium as well as to differentiate stress-induced cardiomyopathies from actual MI.80,81
Prior to the administration of contrast, T2-weighted imaging or T2 mapping can be used to characterize the presence of myocardial edema. Abdel-Aty and colleagues82 have demonstrated that edema imaging depicts acute ischemic injury often within the first 30 minutes from abrupt coronary artery occlusion and even before the development of LGE. Therefore, in the setting of an acute infarction, bright signal observed in T2 imaging techniques predicts the maximal area of myocardium that is at risk for necrosis.
Myocardial salvage relates to a term that defines the difference between the area at risk subtracted from the extent of necrosis as determined with LGE.80,81 As shown in Fig. 16–23, edema involves the entire area of the myocardial wall, whereas the transmural spread of necrosis is variable and is identified with LGE imaging. In the situation where abrupt return of antegrade coronary flow is established or extensive collateral flow is present, the degree of myocardial salvage can be readily identified. Importantly, this region represents an area of risk of reinfarction in patients in whom inadequate coronary artery blood flow recurs.
Three-part figure demonstrating cardiovascular magnetic resonance tissue characteristics associated with acute myocardial infarction (MI). A. A cartoon representation of a short-axis view of the left ventricle. The cartoon demonstrates the left ventricular (LV) cavity (purple), LV myocardium (green), region of microvascular obstruction (dark rim), late gadolinium enhancement (LGE) associated with an infarct (white), and the myocardial area at risk (gray). B. An example of a LGE short-axis plane where the normal LV myocardium is depicted as gray and the cavitary blood is depicted as white. The white arrows demarcate the bright signal intensity associated with LGE evidence of MI. In addition, the leftmost white arrow identifies dark signal intensity within the region of LGE associated with microvascular obstruction (MVO). Because of plugging of the coronary microcirculation, no gadolinium contrast is allowed to reach this area and hence the dark signal intensity associated with MVO. C. A T2-weighted black-blood image is displayed in a short-axis plane in the same location as in B. In this image, the LV cavitary blood is dark and the normal LV myocardium is gray. The yellow arrows demonstrate increased signal intensity within the LV myocardium on the T2-weighted images, highlighting increased edema associated with the myocardial area at risk. Of note, one can subtract the region of infarction and MVO from the total myocardial area at risk and calculate the region of salvageable myocardium after successful coronary arterial revascularization in the setting of acute MI.
One complication associated with acute MI is the development of intramyocardial hemorrhage.83 CMR is well suited to identify intramyocardial hemorrhage utilizing a combination of T2-weighted and T2*-weighted imaging, as well as LGE. T2*-weighted imaging is very useful to identify the presence of hemoglobin degradation products. These products produce a low signal intensity on T2*-weighted images. In a series of 98 individuals sustaining an MI, approximately one-fourth experienced hemorrhagic infarcts that were in turn associated with infarction transmurality, a larger MI size, and reduced LVEF.83 In addition, those with myocardial hemorrhage experienced a greater increase in LV end-systolic volume 4 months after the infarct relative to those without evidence of myocardial hemorrhage. These data suggest that the presence of myocardial hemorrhage identified by T2*-weighted imaging during CMR may predict adverse LV remodeling.