Cardiovascular Magnetic Resonance in Myocarditis: A JACC White Paper
JACC White Paper
Cardiovascular magnetic resonance (CMR) has become the primary tool for noninvasive assessment of myocardial inflammation in patients with suspected myocarditis. The International Consensus Group on CMR Diagnosis of Myocarditis was founded in 2006 to achieve consensus among CMR experts and develop recommendations on the current state-of-the-art use of CMR for myocarditis. The recommendations include indications for CMR in patients with suspected myocarditis, CMR protocol standards, terminology for reporting CMR findings, and diagnostic CMR criteria for myocarditis (i.e., “Lake Louise Criteria”).
Background: Myocarditis
Incidence and Etiology
Incidence and Etiology
In this paper, myocarditis is defined as inflammation of myocardial tissue. Myocarditis has been reported in up to 12% of young adults presenting with sudden death (1–4) and is an important underlying etiology of other myocardial diseases such as dilated (5) and arrhythmogenic right ventricular (6) cardiomyopathy. The incidence of nonfatal myocarditis is likely greater than actually diagnosed, mostly as a result of the challenges of establishing the diagnosis in standard clinical settings.
Infectious disease accounts for most cases in previously healthy patients typically either because of a direct viral infection or post-viral immune-mediated reaction. Myocardial inflammation, however, also may be triggered by reversible and/or irreversible toxic, ischemic, or mechanical injury, drug-related inflammation, transplant rejection, or other immune reactions.
Pathogenesis and Pathology
The pathogenetic features of myocarditis are reviewed in detail elsewhere (7). After the initial injury, local and systemic immune responses activate cytokines and B cells with subsequent edema, additional myocyte injury, and autoantibody production. Although the molecular and cellular pathophysiology may differ between different etiologies, cellular infiltration, edema, necrosis, and (in later stages) fibrotic scars are common features.
Diagnostic Approaches to Myocarditis and Their Limitations
Currently, no single clinical or imaging finding confirms the diagnosis of myocarditis with absolute certainty. Rather, an integrated synopsis, including history, clinical assessment, and noninvasive test results, should be used to diagnose the disease and guide treatment.
History and physical exam
Although of limited specificity, a careful history and thorough clinical assessment have to precede further diagnostic tests. Patients may appear almost normal, may have nonspecific symptoms, but also may present with features of acute myocardial infarction or heart failure with hemodynamic compromise. Physical exams of patients with myocarditis are often unremarkable.
Ventricular functional analysis
Although many patients with myocarditis have regional or global wall motion abnormalities (8–10), dysfunction is not specific to inflammation, and its sensitivity is limited (9,11–13). Biventricular dysfunction in myocarditis, however, was found to be the main predictor of death and transplantation (14).
Electrocardiogram (ECG)
The ECG findings associated with myocarditis may include ST-segment and T-wave changes, Q waves, atrioventricular block, and bundle-branch block. Arrhythmias such as ventricular tachycardia and ventricular fibrillation occur. The diagnostic value of the ECG in myocarditis, however, is limited. Aside from a low specificity, either ST-segment elevation or T-wave inversion is present as the most sensitive ECG criterion in <50% of patients, even during the first weeks of the disease (15).
Biomarkers
Depending on the severity and time of testing during the course of disease, serum biomarkers of myocardial injury such as creatine kinase, creatine kinase-myocardial band, and troponin may be increased. When present, the magnitude of increase as well as the time to clearance is similar to that of a small- to medium-sized myocardial infarction and indicates more severe disease. The prevalence of an increased troponin T in biopsy-proven myocarditis, however, is only 35% to 45% (16).
Biopsy
Endomyocardial biopsy (EMB) is a widely accepted method for diagnosing myocarditis, based upon histopathology, immunohistology, and molecular techniques to identify viral genomes. A Joint Scientific Statement of several professional societies on its use in various clinical scenarios has been published (17).
Some limitations of EMB have to be considered. First, the sensitivity of EMB is limited as the result of so-called sampling error (18–21). Second, severe complications (perforation, tamponade) occur in 0.1% to 0.5%, and the overall complication rate is 6% (17). Third, substantial debate exists regarding diagnostic criteria for analyzing myocardial tissue specimens (22). The utility of the Dallas criteria (23), with inflammatory infiltration and associated myocyte necrosis uncharacteristic for an ischemic event as disease markers, is limited by poor interobserver agreement (24,25).
Immunohistochemistry has a greater sensitivity than standard histopathology for the diagnosis of myocarditis (26,27), and immunohistology protocols and evaluation criteria have been proposed (10,28). Cost, availability, and limited standardization, however, have limited the widespread use of immunohistology and viral genome analysis. Finally, in adults, the recommended indications for endomyocardial biopsy are confined to patients with heart failure (17) and, therefore, EMB is not recommended in many patients with myocarditis.
In summary, history, clinical exam, ECG, and serology have an unsatisfactory diagnostic accuracy in myocarditis. Biopsy, including immunohistochemistry, remains the widely accepted standard, but may not be appropriate for many patients, especially those with less severe disease.
Imaging Modalities Other Than CMR
A detailed review of noninvasive imaging in myocarditis can be found elsewhere (29). Ultrasound studies of the heart in myocarditis typically are performed to visualize associated functional abnormalities, wall thickness, and pericardial effusion (8,30). The diagnostic value of echocardiography is limited by the fact that many patients with less severe myocarditis have a normal echocardiogram and the highly variable echocardiographic findings lack specificity (8).
111Indium antimyosin antibody and 67gallium nuclear imaging have been used to diagnose myocarditis (31). The specificity of these approaches, however, is very limited (32). Nuclear medicine techniques also are hampered by the limited availability of tracers mentioned previously, poor spatial resolution, and radiation issues. In current clinical practice, nuclear medicine is used only rarely to diagnose myocarditis.
CMR in Myocarditis
Published Data
Published Data
The use of CMR imaging offers a unique combination of safety, clarity of anatomical visualization, interobserver consistency, and quantitative accuracy. Furthermore, it allows for the comprehensive use of a wide spectrum of diagnostic targets, especially the modifiable inherent tissue contrast. This modality has become a standard tool in many medical centers and currently is considered by many to be the most versatile and powerful cardiovascular imaging modality.
Since the first description of T2-weighted CMR findings in children with myocarditis by Gagliardi et al. in 1991 (33) and the first controlled clinical study using contrast-enhanced CMR in 1998 (9), numerous investigators have studied the diagnostic utility of noncontrast (11,13,34) and contrast-enhanced (11–13,34–43) CMR in patients with myocarditis. Results have consistently shown the clinical feasibility and high diagnostic accuracy with different single-technique or combined CMR protocols. Tables 1 to 4show a list of published controlled trials on CMR in myocarditis (Table 1), and data on the diagnostic accuracy of left ventricular (LV) dysfunction (Table 2) and of CMR criteria for myocarditis (Table 3: individual criteria; Table 4: combined criteria).
Validation | No. of Patients | No. of Control Patients | |
---|---|---|---|
Friedrich et al., Circulation1998 (9) | Clinical | 19 | 18 |
Laissy et al., Chest2002 (11) | Clinical | 20 | 7 |
Rieker et al., Rofo2002 (36) | Clinical | 11 | 10 |
Laissy et al., Radiology2005 (37)* | Clinical | 24 | 31 |
Abdel-Aty et al., J Am Coll Cardiol2005 (13) | Clinical | 25 | 22 |
Mahrholdt et al., Circulation2006 (40) | Histology | 87 | 26 |
Gutberlet et al., Radiology2008 (34)† | Histology | 48 | 35 |
Yilmaz et al., Heart2008 (43)† | Histology | 55 | 30 |
Total | 289 | 179 |
LV Dysfunction (EF <55%) | Validation | Sensitivity (%) | Specificity (%) | Accuracy (%) | PPV (%) | NPV (%) |
---|---|---|---|---|---|---|
Friedrich et al., Circulation1998 (9) | Clinical | 100 | 100 | 100 | 100 | 100 |
Laissy et al., Chest2002 (11) | Clinical | 62 | 100 | 75 | 100 | 58 |
Laissy et al., Radiology2005 (37)* | Clinical | 46 | 62 | 57 | 37 | 70 |
Abdel-Aty et al., J Am Coll Cardiol2005 (13) | Clinical | 38 | 100 | 61 | 100 | 49 |
Gutberlet et al., Radiology2008 (34) | Histology | 50 | 63 | 55 | 65 | 48 |
Pooled data (n = 276) | 54% | 76% | 64% | 71% | 60% |
Validation | Sensitivity (%) | Specificity (%) | Accuracy (%) | PPV (%) | NPV (%) | |
---|---|---|---|---|---|---|
Early myocardial gadolinium enhancement | ||||||
Friedrich et al., Circulation1998 (9) | Clinical | 84 | 89 | 86 | 89 | 84 |
Laissy et al., Chest2002 (11) | Clinical | 85 | 100 | 89 | 100 | 70 |
Abdel-Aty et al., J Am Coll Cardiol2005 (13) | Clinical | 80 | 68 | 74 | 74 | 75 |
Gutberlet et al., Radiology2008 (34) | Histology | 63 | 86 | 72 | 86 | 63 |
Pooled data (n = 194) | 74 | 83 | 78 | 86 | 70 | |
T2 | ||||||
Rieker et al., Rofo2002 (36) | Clinical | 100 | 50 | 76 | 69 | 100 |
Laissy et al., Chest2002 (11) | Clinical | 45 | 100 | 59 | 100 | 39 |
Abdel-Aty et al., J Am Coll Cardiol2005 (13) | Clinical | 84 | 74 | 79 | 78 | 81 |
Gutberlet et al., Radiology2008 (34) | Histology | 67 | 69 | 67 | 74 | 60 |
Pooled data (n = 178) | 70 | 71 | 70 | 77 | 63 | |
Late enhancement | ||||||
Rieker et al., Rofo2002 (36) | Clinical | 45 | 60 | 52 | 56 | 50 |
Abdel-Aty et al., J Am Coll Cardiol2005 (18) | Clinical | 44 | 100 | 71 | 78 | 62 |
Mahrholdt et al., Circulation2006 (40) | Histology | 95 | 96 | 96 | 99 | 81 |
Gutberlet et al., Radiology2008 (34) | Histology | 27 | 80 | 49 | 65 | 44 |
Yilmaz et al., Heart2008 (43) | Histology | 35 | 83 | 51 | 81 | 38 |
Pooled data (n = 336) | 59 | 86 | 68 | 89 | 53 |
Validation | Sensitivity (%) | Specificity (%) | Accuracy (%) | PPV (%) | NPV (%) | |
---|---|---|---|---|---|---|
T2 + LGE | ||||||
Abdel-Aty et al., J Am Coll Cardiol2005 (13) | Clinical | 40 | 100 | 69 | 100 | 61 |
Gutberlet et al., Radiology2008 (34) | Histology | 17 | 91 | 48 | 73 | 44 |
Pooled data (n = 130) | 25 | 95 | 56 | 86 | 50 | |
T2 and/or LGE | ||||||
Abdel-Aty et al., J Am Coll Cardiol2005 (13) | Clinical | 88 | 74 | 81 | 100 | 85 |
Gutberlet et al., Radiology2008 (34) | Histology | 50 | 57 | 52 | 80 | 25 |
Pooled data (n = 130) | 60 | 66 | 62 | 79 | 43 | |
Any 1 of 3 | ||||||
Abdel-Aty et al., J Am Coll Cardiol2005 (13) | Clinical | 100 | 48 | 75 | 68 | 100 |
Gutberlet et al., Radiology2008 (42) | Histology | 81 | 49 | 67 | 68 | 65 |
Pooled data (n = 130) | 88 | 48 | 70 | 68 | 76 | |
Any 2 of 3 | ||||||
Abdel-Aty et al., J Am Coll Cardiol2005 (13) | Clinical | 76 | 96 | 85 | 95 | 79 |
Gutberlet et al., Radiology2008 (34) | Histology | 63 | 89 | 73 | 88 | 63 |
Pooled data (n = 130) | 67 | 91 | 78 | 91 | 69 |
Although published data on diagnostic accuracy provide solid evidence for the use of CMR in clinical settings, it is important to emphasize that most of these studies were single-center reports and had a small sample size, variable inclusion criteria, and nonuniform patient populations. Furthermore, CMR studies were performed at variable time points after disease onset, used different imaging diagnostic criteria, and mostly did not include biopsy for confirmation.
Furthermore, the specificity was mostly compared with normal control patients or those with myocardial infarction and not to other heart diseases with similar clinical presentation, such as acute coronary syndrome or other secondary cardiomyopathies. Current data do not allow for a clear definition of the diagnostic accuracy of CMR in various clinical, histological, and immunohistochemical subgroups, and data from larger (multicenter) trials with standardized protocols comparing comprehensive CMR studies to biopsy-derived criteria are lacking.
The prognostic value of CMR criteria for myocarditis remains to be defined. In a small study, increased myocardial early gadolinium enhancement ratio at 4 weeks after clinical onset of the disease was associated with an impaired prognosis regarding functional recovery and symptoms after a 3-year follow-up (44). Confirmative studies on the prognostic value of the various parameters are required.
Diagnostic Targets of CMR in Myocarditis
Different from other diagnostic modalities, targets for CMR not only include functional and morphological abnormalities but also tissue pathology as diagnostic features of myocardial inflammation.
Functional abnormalities
The CMR assessment of right ventricular and LV function is very reproducible and thus allows for identifying, quantifying, and following even mild functional abnormalities, if present. In patients with more severe myocarditis, global LV dysfunction is frequent. It is, however, re-emphasized that regional or less severe LV wall motion abnormalities have a low specificity for the underlying pathophysiology.
Pericardial effusion
Pericardial effusion has been reported in 32% to 57% of patients with myocarditis (45–47). Although not specific for myocarditis, its presence is supportive evidence for active inflammation.
Regional distribution and extent and hemodynamic significance of pericardial effusion can be assessed by the use of standard short- and long-axis steady-state free precession (SSFP) images acquired for morphology and function. This sequence type has an inherent T2 sensitivity, rendering pericardial fluid bright signal intensity (Fig. 1A).The differentiation from epicardial fat (which also appears bright) is straightforward: the latter is found around coronary vessels (which are embedded in the epicardial fat layer) or in the AV groove and, in SSFP images, typically separated from effusion by a (single-pixel) thin chemical shift artifact layer, that is, a fine line without signal. Furthermore, fat mostly appears with a slightly lower signal intensity, and effusion may have a more “deformable” appearance through the cardiac cycle. In T1-weighted images (e.g., spin-echo images) fluid has low signal intensity. In phase-sensitive inversion-recovery sequences, however, it may be black or white, depending on the inversion time settings.

Short-Axis CMR Views in a Patient With Clinically Acute Myocarditis
(A)Still frames from a cine series at end-diastole (left)and end-systole (right)showing only very mild septal hypokinesis (arrow)with preserved ejection fraction. Small pericardial effusion is present along the lateral segments (arrowheads). These findings represent 2 supportive criteria for myocarditis. (B)T1-weighted spin-echo images before (left)and shortly after (right)gadolinium administration with early gadolinium accumulation in the septum (arrows). Quantitative evaluation of the signal enhancement (skeletal-muscle normalized myocardial enhancement ratio of ≥4.0 or an absolute enhancement of ≥45%) is required to use information from this pulse sequence as a positive criterion. (C) (Left)T2-weighted spin-echo image with high signal intensity of the septum and lateral wall (arrows). Evidence for regional edema, or a signal intensity ratio of ≥2.0 (signal intensity normalized to skeletal muscle in the same slice), renders T2 findings positive. (Right)Late enhancement image without evidence for significant delay of gadolinium washout. The thin subepicardial layer of high signal intensity in the inferolateral region represents fat.
Small, physiological accumulations of pericardial fluid are not circumferential and may not be considered pathologic. A fluid layer that contains nonfluid components (fibrinous deposits, thrombus) is pathologic.
Morphological abnormalities
A transient increase of wall thickness during myocarditis was first described in echocardiography studies (48) and may serve as a supportive finding during follow-up. A decrease of LV mass during the course of uncomplicated myocarditis was found to be associated with edema as assessed by T2-weighted CMR (49). A transient increase of LV volumes has been observed in the course of myocarditis (9) and may also may serve as retrospective, supportive evidence for recent myocarditis.
Tissue Characterization With CMR
Given the unique potential of CMR to visualize tissue changes, this area is of special interest. As outlined previously, expected tissue pathology in active myocarditis includes intracellular and interstitial edema, capillary leakage, hyperemia, and, in more severe cases, cellular necrosis and subsequent fibrosis (50).
Edema
An important hallmark of inflammatory cell injury is the increased permeability of cellular membranes. Whereas initial membrane defects are of a functional nature, leading to Na+influx and subsequent intracellular edema, a more severe injury allows for a net efflux of water and transmembranous leakage of larger molecules such as troponin, eventually leading to loss of cellular functions.
T2-weighted imaging sensitively detects tissue edema with the long T2 of water-bound protons as the contrast-generating mechanism, resulting in a high signal intensity of edematous tissue (Fig. 1C). Triple inversion recovery turbo spin echo sequences with inversion pulses for fat and blood suppression (51) provide excellent contrast between regional edema and normal myocardium because of the dual suppression of the fat and flowing blood signal. Double inversion recovery sequences may provide a greater signal-to-noise ratio and be used alternatively. Importantly, edema in patients with myocarditis may have a global myocardial distribution and, thus, a quantitative signal intensity analysis of the entire myocardium may be necessary. A high diagnostic accuracy has been shown for this approach in acute inflammatory or ischemic injury (13,34,52).
Regional edema visible on T2-weighted CMR images was not observed in “borderline myocarditis” but could be found in 36% of patients with histologically “active myocarditis” as defined by the Dallas criteria (39). Thus, regional edema may have a limited sensitivity in less severe inflammation. Short-axis views typically provide a more robust image quality than long axis images, although apical slices may have to be discarded because of artifacts related to intraventricular blood signal.
The signal-to-noise ratio of T2-weighted images strongly depends on sequence parameters. Particularly in patients with arrhythmia and other motion artifacts, image quality may not allow for reliable visualization or quantification of edema. Newly developed sequences may yield a more consistent image quality and better diagnostic accuracy than currently used fast spin-echo triple inversion recovery prepared protocols (53,54).
Hyperemia and capillary leak (myocardial early gadolinium enhancement)
Regional vasodilatation is an integral feature of tissue inflammation. The increased blood volume in the inflamed area leads to an increased uptake of contrast agents during the early vascular phase. Because gadolinium-based contrast agents distribute quickly into the interstitial space after administration, this phase lasts for the first minutes after the contrast bolus. Contrast-enhanced fast spin-echo T1-weighted MR during this time can be used to assess experimentally induced myocardial hyperemia (55) and to detect muscular inflammation (56). Accordingly, the purpose of myocardial early gadolinium enhancement ratio (EGEr) is to detect an overall increased volume of gadolinium distribution into the intravascular and interstitial space during the early washout period.
The diagnostic utility of contrast-enhanced T1-weighted imaging in patients with clinically acute and chronic myocarditis has been shown in several studies (9,13,34,35).
Currently, fast spin-echo sequences are used, which are vulnerable to inconsistent image quality in patients with varying heart rate and irregular breathing patterns. New sequences to assess the early phase of gadolinium kinetics may overcome existing limitations of image quality.
Necrosis and fibrosis (late gadolinium enhancement [LGE])
Myocardial LGE specifically reflects irreversible myocardial injury (i.e., necrosis and fibrosis). This type of imaging uses an inversion pulse to decrease the signal response from normal myocardium, thereby highlighting areas with increased accumulation of gadolinium as bright regions.
In earlier stages of necrosis, gadolinium enters the cells through acutely injured cell membranes (7). Hence, the volume of distribution of gadolinium is increased (12) and visualizes myocarditis-related necrosis (Fig. 2).After inflammatory clearance of necrotic regions, a mesh of fibrocytes with a large interstitial component replaces formerly viable tissue, again increasing the volume of distribution for gadolinium into this extracellular space during the late washout period. Thus, the late sequelae of inflammatory tissue damage also can be observed by LGE.

Late Enhancement Patterns in Myocarditis
(A)Normal myocardium with no evidence of irreversible myocyte injury. (B)Regional subepicardial enhancement of the lateral wall (arrow). (C)Subepicardial enhancement of lateral and midwall enhancement of the septal wall (arrows). (D)Diffuse subepicardial enhancement.
Microscopic (57), animal (58), and clinical (59) studies have confirmed the role of LGE imaging as s gold standard for in vivo detection of irreversible myocardial injury associated with myocardial infarction. In patients with myocarditis, several studies have demonstrated a high specificity of LGE for the detection of such injury in myocarditis (12,13,37,38,40). The regional distribution of injury as defined by LGE not only allows differentiating ischemic (with mandatory subendocardial involvement) from nonischemic injury (60), but also may indicate the underlying etiology of the nonischemic insult (61).
As a potential limitation, LGE showed a variable sensitivity to detect active or chronic inflammation, depending on the selection of patients (12,13,34,39,40,43). Using the Dallas criteria, De Cobelli et al. (39) found LGE to be less sensitive in “borderline” myocarditis (44%) than in “active” myocarditis (84%).
One reason may be that active myocarditis may not always lead to large-enough regions of necrotic myocytes to be visually detectable, given the pixel size in CMR images. This contrasts with the situation in ischemic necrosis for which LGE has been shown to be highly sensitive. Therefore, LGE may be insensitive for the detection of symptomatic myocarditis with limited or nonfocal irreversible injury. More studies are needed to address this issue.
Combined use of tissue pathology markers
Two studies have compared all 3 tissue-based markers as well as various combinations of these. Abdel-Aty et al. (13) used combined clinical criteria for active myocarditis, whereas Gutberlet et al. (34) assessed patients with chronic myocarditis, validated against histopathological criteria of myocardial inflammation. In both studies, the approach with the best overall diagnostic accuracy was found by the combined use of all 3 tissue-based CMR parameters, with the presence of at least 2 positive criteria defining the CMR study as positive for myocarditis (Tables 3 and 4).
Indications, Procedure, and Protocol of CMR
Indications for CMR
Indications for CMR
A CMR study should only be performed if patients are symptomatic, if there is sufficient clinical evidence for myocarditis, and if the CMR result will likely affect clinical management. Thus, it is generally indicated in patients with current or persisting symptoms, evidence for significant myocardial injury, and suspected viral etiology. CMR is of potential use in patients with chest pain, elevated troponin, and normal coronary arteries, where it was shown to identify myocarditis in more than 30% of patients (62).
Additional indications may exist for subjects with possible myocarditis being exposed to strenuous physical exercise (e.g., professional athletes) or for patients with otherwise unexplained new ECG findings consistent with myocarditis, even in the absence of symptoms suggestive of myocarditis. Table 5lists recommended criteria for requesting a CMR study in patients with suspected myocarditis.
New Onset or Persisting Symptoms Suggestive of Myocarditis | Plus | Evidence for Recent/Ongoing Myocardial Injury | Plus | Suspected Viral Etiology |
---|---|---|---|---|
Dyspnea ororthopnea orpalpitations oreffort intolerance/malaise orchest pain | Ventricular dysfunction ornew or persisting ECG abnormalities orelevated troponin | History of recent systemic viral disease or previous myocarditis orabsence of risk factors for coronary artery disease or age <35 yrs orsymptoms not explained by coronary stenosis on coronary angiogram orrecent negative ischemic stress test |
The CMR Procedure
The patient should be monitored throughout the session, including ECG, blood pressure, breathing, and O2saturation. Furthermore, communication to the patient should be ensured by the use of intercom devices. A physician trained in cardiac resuscitation should be available. As for all cardiac diagnostic modalities, drugs and equipment for immediate interventions should be within reach.
Typically, patients are examined in a supine position. A dedicated cardiac phased-array surface coil should be used to acquire functional images. It is very important to emphasize that for all sequences used to analyze signal intensity (qualitatively or quantitatively), either a signal intensity correction algorithm or the body coil should be used. The inhomogeneous sensitivity field of surface coils may otherwise lead to false negative (inferolateral wall) or false positive (septum) results.
The coverage of the heart should allow for assessing all 17 LV segments according to published recommendations (63). Images of the apex may be of insufficient image quality and may have to be excluded.
Published data on contrast-enhanced CMR in myocarditis mostly have been obtained with the use of gadolinium gadopentetate dimeglumine and, thus, recommendations are only valid for this substance or compounds with an equivalent pharmacokinetic profile.
The CMR Protocol
Recommended imaging parameters and detailed protocol recommendations are provided in the Online Appendixof this article. CMR sequences generally will be ECG-gated and performed by the use of breath-hold protocols. These recommendations are based on the current evidence as published in peer-reviewed literature as of January 2009. Some of the currently recommended sequences have distinct limitations. Images obtained by T1-weighted spin-echo sequences during free breathing may have limited diagnostic quality, and T2-weighted spin-echo images suffer from an inherently low signal-to-noise ratio. Although new sequences are being tested for these purposes, their value and clinical role remains to be defined.
Evaluation of CMR Images in Suspected Myocarditis
The versatility, accuracy, and reproducibility of CMR and the generally high expectations of referring physicians call for a careful, responsible evaluation of all available parameters. Table 6summarizes CMR findings and proposed terminology in patients with suspected myocarditis.
Normal | CMR Findings Consistent With Myocardial Inflammation | ||||
---|---|---|---|---|---|
Edema | Lack of evidence for myocardial edema | Patchy areas or regions of high T2 signal intensity indicating focal or regional edema* | Subepicardial or septal layer of high T2 signal intensity indicating regional edema | Transmural high T2 signal intensity indicating regional edema, consistent with but not specific for myocardial inflammation | Global high T2 signal intensity indicating global edema† |
Hyperemia Capillary leak | Lack of evidence for increased myocardial early gadolinium enhancement ratio | Increased myocardial early gadolinium enhancement ratio‡ | |||
Irreversible cell injury | Lack of evidence for regional late gadolinium enhancement | Patchy areas of late gadolinium enhancement indicating focal injury | Subepicardial or septal layer of late gadolinium enhancement indicating regional injury | Transmural late gadolinium enhancement, consistent with but not specific for myocardial inflammation | |
Normal | Supportive CMR Findings | ||||
LV dysfunction | Normal LV function | Regional systolic dysfunction | Global systolic dysfunction | ||
Pericardial effusion | Lack of evidence for pericardial effusion | Small pericardial effusion | Moderately large pericardial effusion | Large pericardial effusion without hemodynamic relevance | Large pericardial effusion with hemodynamic relevance |
Edema
Myocardial edema appears as an area of high signal intensity in T2-weighted images (Fig. 1C, left panel). In myocarditis, it may be regional or global. It is important to keep in mind that, in the absence of LGE, edema reflects reversible myocardial injury (52,64).
Regional edema can be identified visually (Fig. 1C), although a quantitative assessment of the signal abnormality seems appropriate. Evaluation software allows for verifying edema as regions with signal intensity more than 2 standard deviations above the mean value of normal tissue. The lower signal-to-noise of T2-weighted images should be considered, limiting the ability to correctly identify small regions of signal inhomogeneity. Thus, it is recommended to consider only areas of at least 10 adjacent pixels with high signal intensity as relevant. Areas with abnormally low signal in T2-weighted images (e.g., fibrotic scars) should not be used for normalization.
In myocarditis, edema may be global and thus not recognizable to the eye. A quantitative analysis by normalizing the signal intensity of the myocardium to that of skeletal muscle has been shown to allow for the detection of a global T2 signal abnormality. Values for the T2 ratio (for calculation, see the Online Appendix) of more than 1.9 indicate myocarditis (13).
Involvement of skeletal muscle in systemic inflammation may limit the sensitivity of a signal intensity analysis normalized to skeletal muscle (11) and should be taken into consideration in patients with evidence for ongoing myositis. Future studies will have to address the diagnostic accuracy in different scenarios.
When analyzing signal intensity, great care should be taken to exclude high signal of inadequately suppressed slowly flowing cavitary blood. This should not be a problem in visual analysis because slow flow signal would have an apparent “subendocardial” location, whereas the T2 signal hyperintensity of myocarditis is almost always subepicardial or transmural. The identification of skeletal muscle to calculate myocardium to skeletal muscle ratio in the same slice may be difficult with a fat-suppressed sequence. The viewing of T2 images side by side with colocalized SSFP or T1-weighted images is recommended to correctly identify skeletal muscle and differentiate it from subcutaneous fat.
Hyperemia and capillary leakage (myocardial early gadolinium enhancement)
The EGEr is defined as an increased normalized gadolinium gadopentetate dimeglumine accumulation in the myocardium during the early washout period. Although sometimes visually appreciated (Fig. 1B), quantitative evaluation of myocardial EGEr is required. Normalization of the signal intensity in T1-weighted images to that of skeletal muscle may be hampered by coexisting myositis. In patients with evidence for skeletal muscle involvement as indicated by a skeletal muscle signal intensity increase of 20% or higher or by a recent history of muscular pain, an absolute myocardial signal intensity increase between pre- and post-gadolinium images of more than 45% should be used as a threshold consistent with myocarditis instead of the normalized myocardial early gadolinium enhancement ratio (11). In patients with irregular breathing patterns or significant arrhythmia, image quality may be reduced or even be nondiagnostic.
Necrosis and fibrosis (LGE)
Several patterns of LGE may be seen in patients with active myocarditis (Fig. 2). Focal signal increases typically are localized to the subepicardial regions of the LV and extend to a variable extent through the ventricular wall. The LGE may be localized in inferolateral and, less frequently, anteroseptal segments (Fig. 1B). However, LGE may be multifocal or diffuse in distribution (Figs. 1C and 1D). As a rule, the subendocardium typically is not involved in an isolated fashion, clearly distinguishing this injury pattern from ischemia-mediated injury. In the basal septum, the LV outflow tract and the membraneous septum may mimic septal LGE in short axis images and lead to false-positive results. Also, a line of increased signal intensity may appear in the basal septum on transverse, long-axis, or short-axis images that may not represent pathologic LGE but may be related to the fusion of the right ventricular moderator band to the right ventricular portion of the interventricular septum.
Comprehensive use of CMR criteria (“Lake Louise Criteria”)
Because of the lack of large-scale multicenter data, current recommendations can only reflect the experts' best-achievable consensus based on currently available literature. It is important to re-emphasize that rigorous test data of the pulse sequences evaluated against the gold standard of myocardial biopsy in clearly defined clinical subsets of patients are still scarce. The sensitivity and specificity as compared with endomyocardial biopsy for the pulse sequences recommended in this article are based on the limited number of patients in controlled trials. At the current time, this needs to be kept in mind when employing CMR for making the diagnosis of myocarditis.
The authors recommend the combined use of all 3 tissue markers. If all sequences can be performed and 2 or more of the 3 tissue-based criteria are positive, myocardial inflammation can be predicted or ruled out with a diagnostic accuracy of 78% (pooled data, Table 4); if only LGE imaging is performed, the diagnostic accuracy is 68% (pooled data, Table 3).
The authors acknowledge that there may be clinical settings that require a greater sensitivity, even if this comes with a reduced specificity, or vice versa. One example may be the use of CMR to assess patients with a high pre-test probability or children with suspected inflammation after cardiac transplantation. It is re-emphasized that both referring physicians and CMR readers should use the reported criteria as part of a comprehensive diagnostic approach, which also includes clinical, functional, and other information. Table 7summarizes the recommended diagnostic CMR criteria for myocardial inflammation.
In the setting of clinically suspected myocarditis,*CMR findings are consistent with myocardial inflammation, if at least 2 of the following criteria are present: |
Regional or global myocardial SI increase in T2-weighted images.† |
Increased global myocardial early gadolinium enhancement ratio between myocardium and skeletal muscle in gadolinium-enhanced T1-weighted images.‡ |
There is at least 1 focal lesion with nonischemic regional distribution in inversion recovery-prepared gadolinium-enhanced T1-weighted images (“late gadolinium enhancement”).§ |
A CMR study is consistent with myocyte injury and/or scar caused by myocardial inflammation if Criterion 3 is present. |
A repeat CMR study between 1 and 2 weeks after the initial CMR study is recommended if |
None of the criteria are present, but the onset of symptoms has been very recent and there is strong clinical evidence for myocardial inflammation. |
One of the criteria is present. |
The presence of LV dysfunction or pericardial effusion provides additional, supportive evidence for myocarditis. |
Follow-Up of Myocarditis by CMR
The decision regarding follow-up of patients with active myocarditis depends on the individual scenario. Anecdotal evidence suggests that CMR studies during the first days of myocarditis may be less sensitive than those obtained 7 days after clinical onset of the disease (65). This may be due to the focal nature of early stages of the disease. Thus, in a patient with strong clinical evidence for myocarditis yet negative criteria in the initial CMR study, a repeat scan may be needed to establish the diagnosis. A follow-up at least 4 weeks after the onset of disease may be useful to differentiate uncomplicated involvement of the myocardium in a systemic viral illness from a complicated course with viral persistence or autoimmunologic disease, as viral clearance usually is completed within the first days after infection and tissue inflammation should not take more than 2 to 3 weeks. Indeed, pilot data indicate a prognostic relevance of persisting CMR markers for inflammation at 4 weeks after onset (44).
Reporting of CMR Results
The report for a CMR study should address the specific questions raised by the referring physician. In suspected myocarditis, this will usually include the inflammatory activity, LV function, and other information such as pericardial effusion, cardiac index, and extent of scarring.
There was consensus that for the time being the presence or absence of the 3 criteria, if acquired, should be reported. The report summary should include components as listed in Table 8.The report should relate quantitative values to published reference values. References may be cited as deemed appropriate.
LV volume and function |
|
Presence or absence of markers for inflammatory activity and injury |
|
Conclusion | On the basis of the presence or absence of 2 or more criteria, considering additional evidence by the presence of LV dysfunction and/or pericardial effusion |
Recommendation for follow-up |
|
It is important to be aware that CMR, like myocardial biopsy, depicts the patient's status at one point in time and cannot characterize acute, chronic, or relapsing forms. These attributes are based on the clinical course rather than imaging (or biopsy) findings. The consensus group therefore recommends against using the terms acute, chronic, and so on with respect to CMR findings, but rather to comment on the presence or absence of “active” or “ongoing” inflammation.
Future Developments of CMR for Myocarditis
The CMR methodology is evolving at a rapid pace. Among numerous interesting developments, many can be expected to be useful for application in myocarditis. As hardware and coil technology are improving, image quality and thus diagnostic yield will be more consistent. But, more importantly, novel approaches for characterizing tissue such as time-resolved assessment of gadolinium wash-out, T1 mapping, T2 mapping, parametric imaging, and the combination of imaging criteria with seromarkers will likely further increase the utility of CMR.
Conclusions
This work provides recommendations on the use of CMR as part of a comprehensive diagnostic approach in patients with suspected myocardial inflammation. The use of CMR appears suitable to identify patients with significant ongoing inflammation, which may be especially important for patients with recurrent or persisting symptoms and in patients with new onset heart failure.
On the basis of published data, we propose a comprehensive CMR protocol to determine the extent and regional distribution of reversible and irreversible myocardial injury, as well as to detect functional and other abnormalities. Furthermore, we suggest consensus criteria providing evidence for or against myocardial inflammation based on CMR findings. We are aware that these recommendations are based on limited data and that not all centers will be able to apply all components of the suggested protocol. New hardware, software, and contrast agent techniques may become available to further improve diagnostic and procedural efficiency of CMR in myocarditis.
1. : "Sudden adult death syndrome and other non-ischaemic causes of sudden cardiac death". Heart 2006; 92: 316.
2. : "Causes of sudden cardiac death in young Australians". Med J Aust 2004; 180: 110.
3. : "Sudden death in the young". Heart Rhythm 2005; 2: 1277.
4. : "Sudden cardiac death". Cardiovasc Pathol 2001; 10: 211.
5. : "From myocarditis to cardiomyopathy: mechanisms of inflammation and cell death: learning from the past for the future". Circulation 1999; 99: 1091.
6. : "Arrhythmogenic right ventricular cardiomyopathy/dysplasia: is there a role for viruses?". Cardiovasc Pathol 2006; 15: 11.
7. : "Advances in the understanding of myocarditis". Circulation 2001; 104: 1076.
8. : "Echocardiographic findings in myocarditis". Am J Cardiol 1988; 62: 285.
9. : "Contrast media-enhanced magnetic resonance imaging visualizes myocardial changes in the course of viral myocarditis". Circulation 1998; 97: 1802.
10. : "Definition of inflammatory cardiomyopathy (myocarditis): on the way to consensus: A status report". Herz 2000; 25: 200.
11. : "MRI of acute myocarditis: a comprehensive approach based on various imaging sequences". Chest 2002; 122: 1638.
12. : "Cardiovascular magnetic resonance assessment of human myocarditis: a comparison to histology and molecular pathology". Circulation 2004; 109: 1250.
13. : "Diagnostic performance of cardiovascular magnetic resonance in patients with suspected acute myocarditis: comparison of different approaches". J Am Coll Cardiol 2005; 45: 1815.
14. : "A prospective study of biopsy-proven myocarditis: prognostic relevance of clinical and aetiopathogenetic features at diagnosis". Eur Heart J 2007; 28: 1326.
15. : "Electrocardiography of myocarditis revisited: clinical and prognostic significance of electrocardiographic changes". Am Heart J 1992; 124: 455.
16. : "Cardiac troponin T in patients with clinically suspected myocarditis". J Am Coll Cardiol 1997; 30: 1354.
17. : "The role of endomyocardial biopsy in the management of cardiovascular disease: a scientific statement from the American Heart Association, the American College of Cardiology, and the European Society of Cardiology: Endorsed by the Heart Failure Society of America and the Heart Failure Association of the European Society of Cardiology". J Am Coll Cardiol 2007; 50: 1914.
18. : "Insensitivity of right ventricular endomyocardial biopsy in the diagnosis of myocarditis". J Am Coll Cardiol 1989; 14: 915.
19. : "Evaluation of postmortem endomyocardial biopsy specimens from 38 patients with lymphocytic myocarditis: implications for role of sampling error". Mayo Clin Proc 1989; 64: 1235.
20. : "Gross and semiquantitative histologic findings in mononuclear cell myocarditis causing sudden death, and implications for endomyocardial biopsy". Am J Cardiol 1993; 72: 952.
21. : "Medical progress: myocarditis". N Engl J Med 2000; 343: 1388.
22. : "Diagnosis of myocarditis: death of Dallas criteria". Circulation 2006; 113: 593.
23. : "Myocarditis: A histopathologic definition and classification". Am J Cardiovasc Pathol 1987; 1: 3.
24. : "The Myocarditis Treatment Trial: design, methods and patients enrollment". Eur Heart J 1995; 16: 162.
25. : "Interobserver variability in the pathologic interpretation of endomyocardial biopsy results". Circulation 1987; 75: 401.
26. : "Induction of major histocompatibility complex antigens within the myocardium of patients with active myocarditis: a nonhistologic marker of myocarditis". J Am Coll Cardiol 1990; 15: 624.
27. : "Active versus borderline myocarditis: clinicopathological correlates and prognostic implications". Heart 2002; 87: 210.
28. : "Report of the 1995 World Health Organization/International Society and Federation of Cardiology Task Force on the Definition and Classification of Cardiomyopathies". Circulation 1996; 93: 841.
29. : "Noninvasive imaging in myocarditis". J Am Coll Cardiol 2006; 48: 2085.
30. : "Echocardiographic findings in fulminant and acute myocarditis". J Am Coll Cardiol 2000; 36: 227.
31. : "Myocarditis in patients with clinical presentation of myocardial infarction and normal coronary angiograms". J Am Coll Cardiol 2001; 37: 786.
32. : "Antimyosin antibody cardiac imaging: its role in the diagnosis of myocarditis". J Am Coll Cardiol 1990; 16: 97.
33. : "Usefulness of magnetic resonance imaging for diagnosis of acute myocarditis in infants and children, and comparison with endomyocardial biopsy". Am J Cardiol 1991; 68: 1089.
34. : "Suspected chronic myocarditis at cardiac MR: diagnostic accuracy and association with immunohistologically detected inflammation and viral persistence". Radiology 2008; 246: 401.
35. : "MRI changes in myocarditis—evaluation with spin echo, cine MR angiography and contrast enhanced spin echo imaging". Clin Radiol 2000; 55: 752.
36. : "Cardiac MRI in suspected myocarditis". Rofo Fortschr Geb Rontgenstr Neuen Bildgeb Verfahr 2002; 174: 1530.
37. : "Differentiating acute myocardial infarction from myocarditis: diagnostic value of early- and delayed-perfusion cardiac MR imaging". Radiology 2005; 237: 75.
38. : "Cardiac magnetic resonance appearance of myocarditis caused by high dose IL-2: similarities to community-acquired myocarditis". J Cardiovasc Magn Reson 2006; 8: 353.
39. : "Delayed gadolinium-enhanced cardiac magnetic resonance in patients with chronic myocarditis presenting with heart failure or recurrent arrhythmias". J Am Coll Cardiol 2006; 47: 1649.
40. : "Presentation, patterns of myocardial damage, and clinical course of viral myocarditis". Circulation 2006; 114: 1581.
41. : "Patterns of myocardial inflammation and scarring in sarcoidosis as assessed by cardiovascular magnetic resonance". Heart 2006; 92: 399.
42. : "Value of MRI in patients with a clinical suspicion of acute myocarditis". Eur Radiol 2007; 17: 2211.
43. : "Coronary vasospasm as the underlying cause for chest pain in patients with PVB19-myocarditis". Heart 2008; 94: 1456.
44. : "Longterm follow-up of patients with acute myocarditis by magnetic resonance imaging". Magma 2003; 16: 17.
45. : "Long-term outcome of acute myocarditis is independent of cardiac enzyme release". Int J Cardiol 2003; 89: 217.
46. : "Fatal myocarditis: morphologic and clinical features". Ital Heart J 2004; 5: 702.
47. : "“Acute pericarditis”: myocardial enzyme release as evidence for myocarditis". Am Heart J 1986; 111: 546.
48. : "Transient ventricular wall thickening in acute myocarditis: a serial echocardiographic and histopathologic study". Jpn Circ J 2001; 65: 863.
49. : "Relation between myocardial edema and myocardial mass during the acute and convalescent phase of myocarditis—a CMR study". J Cardiovasc Magn Reson 2008; 10: 19.
50. : "Clinical and experimental studies in myocarditis". Curr Opin Cardiol 1994; 9: 349.
51. : "An improved MR imaging technique for the visualization of myocardial infarction". Radiology 2001; 218: 215.
52. : "Delayed enhancement and T2-weighted cardiovascular magnetic resonance imaging differentiate acute from chronic myocardial infarction". Circulation 2004; 109: 2411.
53. : "T2-prepared SSFP improves diagnostic confidence in edema imaging in acute myocardial infarction compared to turbo spin echo". Magn Reson Med 2007; 57: 891.
54. : "ACUT2E TSE-SSFP: a hybrid method for T2-weighted imaging of edema in the heart". Magn Reson Med 2008; 59: 229.
55. : "MRI detection of myocardial perfusion changes by gadolinium-DTPA infusion during dipyridamole hyperemia". Magn Reson Med 1989; 10: 246.
56. : "Magnetic resonance imaging of local soft tissue inflammation using gadolinium-DTPA". Acta Radiol 1987; 28: 79.
57. : "Myocardial magnetic resonance imaging contrast agent concentrations after reversible and irreversible ischemic injury". Circulation 2002; 105: 224.
58. : "Relationship of MRI delayed contrast enhancement to irreversible injury, infarct age, and contractile function". Circulation 1999; 100: 1992.
59. : "The use of contrast-enhanced magnetic resonance imaging to identify reversible myocardial dysfunction". N Engl J Med 2000; 343: 1445.
60. : "Detection of myocarditis by contrast-enhanced MRI in patients presenting with acute coronary syndrome but no coronary stenosis". J Magn Reson Imaging 2007; 25: 957.
61. : "Delayed enhancement cardiovascular magnetic resonance assessment of non-ischaemic cardiomyopathies". Eur Heart J 2005; 26: 1461.
62. : "The role of cardiovascular magnetic resonance in patients presenting with chest pain, raised troponin, and unobstructed coronary arteries". Eur Heart J 2007; 28: 1242.
63. : "Standardized myocardial segmentation and nomenclature for tomographic imaging of the heart: a statement for healthcare professionals from the Cardiac Imaging Committee of the Council on Clinical Cardiology of the American Heart Association". Circulation 2002; 105: 539.
64. : "Retrospective determination of the area at risk for reperfused acute myocardial infarction with T2-weighted cardiac magnetic resonance imaging: histopathological and displacement encoding with stimulated echoes (DENSE) functional validations". Circulation 2006; 113: 1865.
65. : "Noninvasive diagnosis of acute myocarditis by contrast-enhanced magnetic resonance imaging—response to the author". Circulation 1999; 99: 459.
1. : "Sudden adult death syndrome and other non-ischaemic causes of sudden cardiac death". Heart 2006; 92: 316.
2. : "Causes of sudden cardiac death in young Australians". Med J Aust 2004; 180: 110.
3. : "Sudden death in the young". Heart Rhythm 2005; 2: 1277.
4. : "Sudden cardiac death". Cardiovasc Pathol 2001; 10: 211.
5. : "From myocarditis to cardiomyopathy: mechanisms of inflammation and cell death: learning from the past for the future". Circulation 1999; 99: 1091.
6. : "Arrhythmogenic right ventricular cardiomyopathy/dysplasia: is there a role for viruses?". Cardiovasc Pathol 2006; 15: 11.
7. : "Advances in the understanding of myocarditis". Circulation 2001; 104: 1076.
8. : "Echocardiographic findings in myocarditis". Am J Cardiol 1988; 62: 285.
9. : "Contrast media-enhanced magnetic resonance imaging visualizes myocardial changes in the course of viral myocarditis". Circulation 1998; 97: 1802.
10. : "Definition of inflammatory cardiomyopathy (myocarditis): on the way to consensus: A status report". Herz 2000; 25: 200.
11. : "MRI of acute myocarditis: a comprehensive approach based on various imaging sequences". Chest 2002; 122: 1638.
12. : "Cardiovascular magnetic resonance assessment of human myocarditis: a comparison to histology and molecular pathology". Circulation 2004; 109: 1250.
13. : "Diagnostic performance of cardiovascular magnetic resonance in patients with suspected acute myocarditis: comparison of different approaches". J Am Coll Cardiol 2005; 45: 1815.
14. : "A prospective study of biopsy-proven myocarditis: prognostic relevance of clinical and aetiopathogenetic features at diagnosis". Eur Heart J 2007; 28: 1326.
15. : "Electrocardiography of myocarditis revisited: clinical and prognostic significance of electrocardiographic changes". Am Heart J 1992; 124: 455.
16. : "Cardiac troponin T in patients with clinically suspected myocarditis". J Am Coll Cardiol 1997; 30: 1354.
17. : "The role of endomyocardial biopsy in the management of cardiovascular disease: a scientific statement from the American Heart Association, the American College of Cardiology, and the European Society of Cardiology: Endorsed by the Heart Failure Society of America and the Heart Failure Association of the European Society of Cardiology". J Am Coll Cardiol 2007; 50: 1914.
18. : "Insensitivity of right ventricular endomyocardial biopsy in the diagnosis of myocarditis". J Am Coll Cardiol 1989; 14: 915.
19. : "Evaluation of postmortem endomyocardial biopsy specimens from 38 patients with lymphocytic myocarditis: implications for role of sampling error". Mayo Clin Proc 1989; 64: 1235.
20. : "Gross and semiquantitative histologic findings in mononuclear cell myocarditis causing sudden death, and implications for endomyocardial biopsy". Am J Cardiol 1993; 72: 952.
21. : "Medical progress: myocarditis". N Engl J Med 2000; 343: 1388.
22. : "Diagnosis of myocarditis: death of Dallas criteria". Circulation 2006; 113: 593.
23. : "Myocarditis: A histopathologic definition and classification". Am J Cardiovasc Pathol 1987; 1: 3.
24. : "The Myocarditis Treatment Trial: design, methods and patients enrollment". Eur Heart J 1995; 16: 162.
25. : "Interobserver variability in the pathologic interpretation of endomyocardial biopsy results". Circulation 1987; 75: 401.
26. : "Induction of major histocompatibility complex antigens within the myocardium of patients with active myocarditis: a nonhistologic marker of myocarditis". J Am Coll Cardiol 1990; 15: 624.
27. : "Active versus borderline myocarditis: clinicopathological correlates and prognostic implications". Heart 2002; 87: 210.
28. : "Report of the 1995 World Health Organization/International Society and Federation of Cardiology Task Force on the Definition and Classification of Cardiomyopathies". Circulation 1996; 93: 841.
29. : "Noninvasive imaging in myocarditis". J Am Coll Cardiol 2006; 48: 2085.
30. : "Echocardiographic findings in fulminant and acute myocarditis". J Am Coll Cardiol 2000; 36: 227.
31. : "Myocarditis in patients with clinical presentation of myocardial infarction and normal coronary angiograms". J Am Coll Cardiol 2001; 37: 786.
32. : "Antimyosin antibody cardiac imaging: its role in the diagnosis of myocarditis". J Am Coll Cardiol 1990; 16: 97.
33. : "Usefulness of magnetic resonance imaging for diagnosis of acute myocarditis in infants and children, and comparison with endomyocardial biopsy". Am J Cardiol 1991; 68: 1089.
34. : "Suspected chronic myocarditis at cardiac MR: diagnostic accuracy and association with immunohistologically detected inflammation and viral persistence". Radiology 2008; 246: 401.
35. : "MRI changes in myocarditis—evaluation with spin echo, cine MR angiography and contrast enhanced spin echo imaging". Clin Radiol 2000; 55: 752.
36. : "Cardiac MRI in suspected myocarditis". Rofo Fortschr Geb Rontgenstr Neuen Bildgeb Verfahr 2002; 174: 1530.
37. : "Differentiating acute myocardial infarction from myocarditis: diagnostic value of early- and delayed-perfusion cardiac MR imaging". Radiology 2005; 237: 75.
38. : "Cardiac magnetic resonance appearance of myocarditis caused by high dose IL-2: similarities to community-acquired myocarditis". J Cardiovasc Magn Reson 2006; 8: 353.
39. : "Delayed gadolinium-enhanced cardiac magnetic resonance in patients with chronic myocarditis presenting with heart failure or recurrent arrhythmias". J Am Coll Cardiol 2006; 47: 1649.
40. : "Presentation, patterns of myocardial damage, and clinical course of viral myocarditis". Circulation 2006; 114: 1581.
41. : "Patterns of myocardial inflammation and scarring in sarcoidosis as assessed by cardiovascular magnetic resonance". Heart 2006; 92: 399.
42. : "Value of MRI in patients with a clinical suspicion of acute myocarditis". Eur Radiol 2007; 17: 2211.
43. : "Coronary vasospasm as the underlying cause for chest pain in patients with PVB19-myocarditis". Heart 2008; 94: 1456.
44. : "Longterm follow-up of patients with acute myocarditis by magnetic resonance imaging". Magma 2003; 16: 17.
45. : "Long-term outcome of acute myocarditis is independent of cardiac enzyme release". Int J Cardiol 2003; 89: 217.
46. : "Fatal myocarditis: morphologic and clinical features". Ital Heart J 2004; 5: 702.
47. : "“Acute pericarditis”: myocardial enzyme release as evidence for myocarditis". Am Heart J 1986; 111: 546.
48. : "Transient ventricular wall thickening in acute myocarditis: a serial echocardiographic and histopathologic study". Jpn Circ J 2001; 65: 863.
49. : "Relation between myocardial edema and myocardial mass during the acute and convalescent phase of myocarditis—a CMR study". J Cardiovasc Magn Reson 2008; 10: 19.
50. : "Clinical and experimental studies in myocarditis". Curr Opin Cardiol 1994; 9: 349.
51. : "An improved MR imaging technique for the visualization of myocardial infarction". Radiology 2001; 218: 215.
52. : "Delayed enhancement and T2-weighted cardiovascular magnetic resonance imaging differentiate acute from chronic myocardial infarction". Circulation 2004; 109: 2411.
53. : "T2-prepared SSFP improves diagnostic confidence in edema imaging in acute myocardial infarction compared to turbo spin echo". Magn Reson Med 2007; 57: 891.
54. : "ACUT2E TSE-SSFP: a hybrid method for T2-weighted imaging of edema in the heart". Magn Reson Med 2008; 59: 229.
55. : "MRI detection of myocardial perfusion changes by gadolinium-DTPA infusion during dipyridamole hyperemia". Magn Reson Med 1989; 10: 246.
56. : "Magnetic resonance imaging of local soft tissue inflammation using gadolinium-DTPA". Acta Radiol 1987; 28: 79.
57. : "Myocardial magnetic resonance imaging contrast agent concentrations after reversible and irreversible ischemic injury". Circulation 2002; 105: 224.
58. : "Relationship of MRI delayed contrast enhancement to irreversible injury, infarct age, and contractile function". Circulation 1999; 100: 1992.
59. : "The use of contrast-enhanced magnetic resonance imaging to identify reversible myocardial dysfunction". N Engl J Med 2000; 343: 1445.
60. : "Detection of myocarditis by contrast-enhanced MRI in patients presenting with acute coronary syndrome but no coronary stenosis". J Magn Reson Imaging 2007; 25: 957.
61. : "Delayed enhancement cardiovascular magnetic resonance assessment of non-ischaemic cardiomyopathies". Eur Heart J 2005; 26: 1461.
62. : "The role of cardiovascular magnetic resonance in patients presenting with chest pain, raised troponin, and unobstructed coronary arteries". Eur Heart J 2007; 28: 1242.
63. : "Standardized myocardial segmentation and nomenclature for tomographic imaging of the heart: a statement for healthcare professionals from the Cardiac Imaging Committee of the Council on Clinical Cardiology of the American Heart Association". Circulation 2002; 105: 539.
64. : "Retrospective determination of the area at risk for reperfused acute myocardial infarction with T2-weighted cardiac magnetic resonance imaging: histopathological and displacement encoding with stimulated echoes (DENSE) functional validations". Circulation 2006; 113: 1865.
65. : "Noninvasive diagnosis of acute myocarditis by contrast-enhanced magnetic resonance imaging—response to the author". Circulation 1999; 99: 459.
Footnotes
Dr. Friedrich is a shareholder and advisor for Circle Cardiovascular Imaging, Inc., Calgary, Alberta, Canada. One of the meetings of the Consensus Group was in part supported by nonrestricted grants from Siemens Medical Solutions Canada and from Berlex Canada Inc. None of the sponsors was involved in the writing process.