Study population
We retrospectively analysed 102 patients referred to our institution for suspected acute myocarditis. Exclusion criteria were defined as follows: evidence of coronary artery disease, valvular diseases or cardiomyopathies; systemic pathologies; pacemaker or implantable cardiac defibrillator; renal insufficiency or risk of nephrogenic systemic fibrosis (glomerular filtration < 30 ml/min/1.73 m
2); contrast media allergies; pregnancy or nursing; clinical history > 30 days [
11]. 42 (42/102, 41.1%) also underwent EMB.
Patient’s categorization was based on well-defined clinical features, as previously addressed by our group [
21]:
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Those who presented with chest pain, increase in T-Troponin serum level (≥ 0.014 μg/ml) and ST-T tract elevation were grouped in the IL onset
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Patients with systolic impairment (ejection fraction < 54%), left ventricle (LV) dilation and heart failure symptoms in the absence of ECG ST-T abnormalities were categorized as CM;
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Subjects with new onset arrhythmias (atrial fibrillation, ventricular arrhythmias, high-degree atrio-ventricular block or bundle branch block) with or without heart failure symptoms were grouped in the AR pattern.
The categorization of clinical presentations was performed by a blinded radiologist at the time of the database preparation. Local ethic committee approved our study.
CMR protocol
After having obtained written informed consent, CMR was performed on a 1.5 T scanner (Magnetom Avanto, Siemens medical systems, Erlangen, Germany), using body and phased array coils.
A single dose of 0.25 ml/kg of gadoteric acid (Claricyclic, GE healthcare, Chicago, Illinois, USA) was injected intravenously at a flow rate of 2 ml/s.
Protocol included cine steady-state free precession (cine-SSFP) acquired during breath-holds in short-axis (from the base to the apex, 10–12 slices), 2-chamber, and 4-chamber planes (TR: 51.3 ms, TE: 1.21 ms, flip angle: 45°, slice thickness: 8 mm, matrix: 256 × 256, field of view: 340–400 mm, voxel size: 2.0 × 1.3 × 8.0 mm). T2-weighted breath-hold black-blood STIR were obtained using a segmented turbo spin echo triple inversion recovery technique on short axis (from the base to the cardiac apex, 8–10 slices), 2 chambers and 4 chambers planes (TR: 2 R–R intervals, TE: 75 ms, flip angle 180°, TI: 170 ms, slice thickness: 8 mm, Field of view: 340–400 mm, matrix: 256 × 256, voxel size: 2.3 × 1.3 × 8 mm). T1-weighted turbo spin echo (TSE) images were acquired with a non–electrocardiogram (ECG)-gated sequence before and immediately after contrast media administration on the same 4–5 axial slices.
A phase sensitive inversion recovery gradient echo (PSIR-GRE) contrast-enhanced sequence was used 10–15 min after gadolinium injection for the LGE (TI: 250–300 ms, TR: 9.6 ms; TE: 4.4 ms; matrix: 256 × 208; flip angle 25°; slice thickness 5.0 mm; slice spacing 5.0 mm).
For T1-mapping, we used a Modified Look Locker Inversion Recovery (MOLLI) sequence, with a 5(3)3 scheme. MOLLI were acquired in three axial slices (basal, mid-ventricular and apical planes) and in four-chambers view, before contrast agent administration and 15 min after Gadolinium injection (TR: 314 ms; TE: 1.12 ms; flip angle: 35°; TI: 200 ms; slice thickness: 8 mm; field of view: 340–400 mm; matrix: 256 × 256; voxel size: 2.1 × 1.4 × 8 mm).
T2 mapping was acquired with a T2-3pt GRE in short axis through basal, mid ventricular and apical planes (TR: 239 ms; TE: 1.13 ms; Flip angle: 12°; Slice thickness: 8 mm; field of view 340–400 mm; matrix 256 × 256; voxel size: 2.5 × 1.9 × 8 mm).
Images analysis
Images were analysed in blind using a dedicated software (Cvi42, Calgary, Canada) by two radiologists with 2 years and 10 years of experience, respectively.
Global and regional ventricular function were assessed using cine-SSFP. Endocardial and epicardial contours were traced on end-diastolic and end-systolic images acquired in short axis planes, in order to determine left ventricular volumes and ejection fraction (EF).
The presence of oedema was evaluated both with T2w-STIR sequences and with T2 mapping. As regards STIR images, a visual assessment of oedema was performed with a signal intensity (SI) > 2 standard deviation (SD) above the remote myocardium. For the semi-quantitative analysis, we used the T2 ratio technique in order to relate the SI of the myocardium to that of the skeletal muscle. We outlined endocardial and epicardial contours in the short axis planes and we drew a Region of Interest (ROI) within a visible skeletal muscle. A ratio ≥ 2 was considered positive for oedema [
19]. For T2 mapping sequences, we manually traced endocardial and epicardial contours throughout basal, mid and apical slice, and positioned a reference point in the anterior interventricular junction. Thanks to our dedicated software, we were able to identify T2 values for each AHA segment [
22]. Then, we calculated mean slice T2 values oedema for each plane. We considered the presence of oedema for mean slice T2 values of more than 50 ms.
Hyperaemia was evaluated with T1-TSE sequences. We traced endocardial and epicardial contours in axial slices acquired before gadolinium injection and then copied contours in slices acquired immediately after contrast media administration. We also drew a ROI within a visible skeletal muscle in order to calculate EGE ratio (EGEr). Hyperaemia was considered to be positive with an EGEr ≥ 4 or with an absolute increase in myocardial SI of 45% in the contrast-enhanced T1-TSE as compared to the pre-contrast images [
20].
As regards necrosis/fibrosis, LGE was identified with a signal intensity > 5 SD [
23] above the remote myocardium and a non-ischemic pattern of distribution (subepicardial or mesocardial or patchy enhancement) [
19].
T1 mapping analysis was performed tracing endocardial and epicardial contours on the basal, mid and apical slices acquired before and 15 min after Gadolinium injection. A ROI was drawn within the LV cavity in order to obtain T1 value of the blood pool. Finally, a reference point was positioned in the anterior interventricular junction.
Our software identified native T1 values and calculated extracellular volume (ECV) for each AHA segment [
22] according to the formula described elsewhere [
24]. Haematocrit value was acquired within 24 h before the scan.
Native T1 mapping was considered to be pathological with mean slice T1 values of more than 1050 ms; ECV was identified as pathological with a mean slice percentage ≥ 28%.
Statistical analysis
Statistical analysis was performed using Medcalc software Ltd (Ostend, Belgium).
The clinical and demographic features were compared using a two-way Chi-Squared Test. Kruskal–Wallis test was used for comparing ventricular functional parameters between the three population (IL, CM and AR).
Inter-observer agreement and the level of agreement between old and new LLC were assessed with Cohen’s k test. Agreement based on k values was interpreted as follows: below 0.4 as poor, between 0.41 and 0.60 as moderate agreement, between 0.61 and 0.80 as substantial agreement, and between 0.81 and 1 as almost perfect. McNemar’s test (MNT) was used to compare the diagnostic proportion between oLLC and nLLC among different clinical presentations. Diagnostic accuracy was calculated only in the selected subcohort of patients who underwent EMB, as the proportion between true positive and true negative and is expressed as a percentage followed by Clopped-Pearson Confidence Interval.
The net reclassification improvement (NRI) and the net absolute reclassification improvement (NARI) were also calculated.
A p-value < 0.05 was considered statistically significant.