DISCUSSION
Relation between ECG abnormalities and LGE on CMR
Spatial correspondence between ECG findings and LGE areas on CMR Diagnostic value of ECG
ECG findings in monitoring acute viral myocarditis Strengths of the study
1
ECG abnormalities during an episode of acute myocarditis and its follow-up, beyond the diagnostic
value.
Camille PERAULT
a,b, Floriane AUCLAIR
a,b, Yoann BOUILLAUD
a,b, Pascaud Adrien
a,b, Fabrice PRUNIER
a,b, Serge WILLOTEAUX
a,c, Alain FURBER
a,b,
Loïc BIERE
a,ba Department of Cardiology, University hospital of Angers, France
b UMR CNRS 6015 - INSERM U1083, Institut MitoVasc, University of Angers, Angers, France
c Department of Radiology, University Hospital of Angers, Angers, France
ABSTRACT
Introduction: There are few studies to describe the changes in ECG findings during myocarditis. Cardiac magnetic resonance (CMR) is on top of acute diagnosis and prognosis after myocarditis, providing new insights into myocardial healing and phenotypes.
The objective of this study was to correlate ECG findings with acute myocarditis CMR phenotype and changes over time and to assess whether ECG is a significant tool to identify healed myocarditis.
Methods: We performed a retrospective analysis of 103 patients who presented CMR-proven acute viral myocarditis between January 2008 and July 2018. Follow-up ECG and CMR were obtained in 62 patients.
Results: ST segment elevation (STE) (n= 64, 62%) and T wave inversion (invT) (n= 21, 20%) were the most frequent ECG abnormalities on admission. Mean age was 33±16 years. 56 patients (86%) were male, 39 (63%) presented with recent infectious syndrome and 57 (92%) had chest pain on hospital admission. InvT patients were older (p=0.022). There was no correlation between STE or invT location and LGE areas on CMR. InvT patients had a lower LVEF (p=0.029) and presented more transmural LGE (p=0.032). STE patients presented more frequent midwall LGE. On follow-up CMR, invT (n=10) was related to larger extent of LGE (p=0.002). There was no difference between patients with normal ECG and abnormal ECG about changes in LVEF (p=0.649), LGE extent (p=0.501), LVEDV index (p=0.362), LVESV index (p=0.771) and LVM index (p=0.503).
3 Conclusion: There was no significant difference in the regression of pre-existing CMR abnormalities between the normal and abnormal ECG group during follow-up. A normal ECG did not exclude the diagnosis, neither complete healing. STE and invT correlated with LGE pattern. Despite the absence of spatial correspondence between ECG and CMR findings, invT presence related with greater extent of LGE at follow-up. InvT might be considered as a surrogate marker for prognosis.
Keywords: ECG, CMR, acute viral myocarditis, ST segment elevation, T wave inversion.
INTRODUCTION
Myocarditis is an inflammatory pathology of the myocardium, commonly due to a viral or bacterial pathogen (1), and related with a dramatic 0.5% of hospital admissions for cardiovascular disease mainly in young, and usually male subjects (2). Often with a benign course, the temporary myocardial injury may lead to heart failure or fatal ventricular arrhythmia (3).
Along with symptoms, resting electrocardiogram (ECG) is one of the simple tools to guide us to the diagnosis of myocarditis (4). The most common anomalies are T wave inversion (invT) and the ST segment elevation (STE); followed by supraventricular or ventricular arrhythmias and atrioventricular or intraventricular conduction abnormalities (3). In recent years, cardiac magnetic resonance imaging (CMR) has become the first-intention non-invasive diagnostic tool in non-severe forms (5). It combines functional analysis with myocardial tissue characterisation, brought together under the “Lake Louise Criteria” (6), indicating myocardial edema by hyperintense or diffuse T2-weighted signal or myocardial enhancement after T1-weighted gadolinium injection, hyperemia by early enhancement, or late evidence of myocardial necrosis or fibrosis. At least one month after an episode of acute myocarditis, experts recommend to perform a follow-up CMR to assess myocardial healing and identify still ongoing myocardial inflammation – that is considered to increase the risk of progression towards dilated cardiomyopathy (7). Recent evidences pointed LGE presence and extent to mark prognosis after myocarditis (8), (9). While verifying the normalisation of CMR findings may be clinically relevant, CMR remains poorly available and expensive. Whether the use of a longitudinal assessment of ECG as a surrogate marker for cardiac healing after myocarditis
5 The objective of this study was to correlate ECG findings with acute myocarditis CMR phenotype and changes over time and to assess whether ECG is a significant tool to identify healed myocarditis.
MATERIALS AND METHODS
Study population
We retrospectively screened 103 patients with acute myocarditis diagnosed by CMR in one single universitary hospital center between January 2008 and July 2018. Inclusion criteria were: (1) acute new-onset symptoms compatible with the diagnosis of myocarditis; (2) troponin release; (3) CMR diagnosis of myocarditis; and (4) absence of coronary artery disease. CMR diagnosis was based on modified Lake-Louise criteria (7) with the presence of LGE on post-contrast images in every patient, and T2-weighted (T2W) which was non mandatory as long as clinical presentation was timely related to CMR findings. Coronary artery disease was ruled out by coronary angiography in 44 (42%) patients, by CT-scan in 4 (4%) patients. The remaining 55 (53%) patients were considered as having a low pretest probability of coronary artery disease. ECGs were available in 103 patients at admission and at hospital discharge, then 87 at follow-up. Of those, 62 patients had follow-up CMR (Figure 1).
Clinical characteristics were collected from medical records. The study protocol was approved by local ethic committee and in respect with Helsinki conference.
ECG procedure and criteria
Standard 12-lead ECGs were analysed with a paper speed of 25 mm/s and amplification of 10 mm/mV (Figure 2). Electrocardiographic data were evaluated by two cardiologists (CP,
7 (32% for STE and 25% for invT), a third cardiologist reanalysed the tracing (LB). The first ECG (ECG 1) analysed was recorded at the fist medical contact either by mobile intensive care units, Emergency Department or cardiac intensive care unit, and obtained 1 [interquartile range (IQR) 0;4] days after symptoms onset. At hospital discharge, another 12-lead ECG (ECG 2) was recorded 5 [IQR 4;6] days after admission. At last, follow-up ECG (FU ECG) was selected as the timely closest to follow-up CMR (FU CMR) and recorded 102 [IQR 61;164] days after initial admission.
ECGs were evaluated according to the recommendations for the standardization and interpretation of the electrocardiogram published by AHA/ACCF/HRS (10), (11). QRS width and axis were measured. Conduction disturbances (bundle branch block, AV-block, sinus dysfunction), premature atrial or ventricular contraction so as atrial and ventricular arrythmia were collected. Sustained ventricular tachycardia lasted at least 30 seconds.
ECG findings’ definition were as follow:
Low voltage as QRS amplitude ≤10 mV in precordial leads and ≤5 mV in peripheral leads.
InvT was measured and confirmed if ≥0.1 mV deep in two or more leads except aVR. STE was measured and defined after the J point in 2 contiguous leads with the cut off points of ≥0.2 mV in leads V2–V3, and/or ≥0.1 mV in other leads. ST depression was considered if ≥0.1 mV. Q-wave was determined as >0.3 mV in depth and/or >40 ms in duration in at least 2 contiguous leads except aVR (8) . QT interval duration was measured and corrected according to the Bazett’s formula; QT was prolonged if > 450ms for men or 460ms for women.
The ECG findings were localized across the 12 leads in the following regions: septal (leads V1 and V2), anterior (leads V2 to V4), apical (V4), high lateral (aVL and DI), bottom lateral (V5-V6), and inferior (DII, DIII, aVF). Localization was considered as diffuse when affected ≥ 3 regions (except apical).
Normal ECG was defined as the absence of any of the above parameters.
CMR protocol
CMR was performed with a 1,5 or 3 Tesla imager (Avanto, Siemens, Erlangen, Germany) 9 [IQR 4; 17] days after symptoms onset and repeated 100 [IQR 91; 125] days thereafter.
Functional parameters were determined with cine imaging using a segmented steady-state free precession pulse sequence in multiple short-axis and four-chamber views covering the entire left ventricle. Typical in-plane resolution was 1.6×1.9 mm, with a section thickness of 7.0 mm (repetition time/echo time: 2.6 ms/1.3 ms; flip angle: 80°; matrix: 256×208;
temporal resolution: 35–45 ms). T2W inversion recovery prepared fast-spin echo sequence was performed on a stack of contiguous short axis views covering the entire LV in mid-diastole;
slice thickness/gap 7/0,8mm; TR (4000ms); TE 60-70 ms; FOV 264*385; matrix 176*320;
flip angle 180°. Late gadolinium enhancement (LGE) sequences were performed 9-12 min after gadolinium-based contrast agent administration (Dotarem®, Laboratoires Guerbet, Roissy-Charles de Gaulle, France) with acumulative dose of 0.2 mmol/kg of body weight, and a two-dimensional segmented inversion recovery gradient-echo pulse sequence. Typical in-plane resolution was 1.68×1.68 mm. Section thickness was 7.0 mm (TE: 4.66 ms; flip angle: 30°;
imaging was triggered to every other heartbeat; matrix: 256×208). The inversion time was individually adjusted to null normal myocardium.
CMR imaging analysis
9 The CMR images were transferred to a workstation for analysis and calculation (QMass MR 7.2, Medis, Leiden, The Netherlands). The images were interpreted on purpose for this study, by a single experienced cardiologist, blinded to clinical data. On all short-axis cine slices, the endocardial and epicardial borders were outlined manually on diastolic and end-systolic frames, excluding the trabeculae and papillary muscles. LV end-diastolic volume (LVEDV), end-systolic volume (LVESV), and mass were determined and indexed to body surface area (12). The presence of T2W or LGE hypersignal were reported. LGE pattern was classified as transmural, epicardial, endocardial, mid-wall and patchy (8). LGE localisation was reported on a 17 segments model. Segments were grouped into region: anterior (segments
#1, 7 and 13), lateral (#5, 6, 11, 12 and 16), inferior (#4, 10 and 15), septal (#2, 3, 8,9, and 14) and apical (#13,14 and 17). LGE extent was then measured and given in grams (8).
Statistical analysis
Continuous variables were related as mean±Standard Deviation (SD) or as median [interquartile range [IQR]]. Categorical variables were expressed as a number and percentage.
Between-group differences were assessed using the Pearson χ2 test for categorical data on no-matched sample and Cochran’s Q test for categorical data on matched sample. Baseline clinical presentation, biology and CMR findings were related with ECG on discharge (ECG 2).
ECG during follow-up (FU ECG) were related with CMR data during follow-up (FU CMR). All tests were performed with a type I error set at 0.05. Statistical analysis was performed using SPSS version 20.0 (IBM Inc., Chicago, IL).
RESULTS
Baseline clinical characteristics
62 patients, included in a follow-up analysis, were studied. Mean age was 33±16 years.
56 patients (86%) were male, 39 (63%) presented with recent infectious syndrome and 57 (92%) had chest pain on hospital admission. Patients had few cardiovascular risk factors. CRP was 40± 51 mg/L (n=58) (Table 1). Mean LVEF was 55±9%, LGE extent was 9±9 gr. LGE appeared as subepicardial in 56 (90%) cases, transmural in 11 (18%), and mid-ventricular in 15 (24%). Predominant distribution was inferior (n=46, 74%) and lateral (n=52, 84%) (Table III).
ECG characteristics
ECG findings are given in table II. Overall, normal ECG was found in 19 (18%) at admission, 28 (27%) at hospital discharge and in 59 (68%) patients at follow-up. STE (n=64, 62%) and invT (n=21, 20%) were the most frequent ECG abnormalities. 11 (11%) patients had both STE and invT on the hospital admission ECG. InvT maximal amplitude was 0.23±0.14 mV, and STE was 0.23±0.10 mV. Out of 64 STE patients, 40 (63%) presented with concave STE, and 15 (23%) convex STE. Atrio-ventricular block was found in 3 patients on admission (2 first degree AV block and 1 second degree AV block), and in 1 patient with first degree AV
11 During hospitalization, 15 patients presented non-sustained ventricular tachycardia; 3 patients presented supraventricular tachycardia and 2 patients had a sinus dysfunction. There was no sustained ventricular tachycardia recorded.
Table I showed baseline characteristics about STE and InvT patterns. InvT patients were significantly older with more dyslipidemia, presented less often chest pain and had less aspirin prescription. STE patients had a trend with a lower BMI. No difference was found about peak of troponin.
ECG abnormalities and CMR parameters
3.1. Baseline: CMR findings and correlation with STE and invT
Initial CMR (T0 CMR) was performed 9 [IQR 4; 17] days after symptom-onset. LVEF was 55±9%. LVM index (LVMI) were 59±12g/m². LVEDV index (LVEDI) and LVESV (LVESVI) index were respectively 94±18 ml/m² and 43±12 ml/m². T2-weighted hypersignal was present in 41 patients (66%).
STE patients (ECG 2) presented a trend for smaller LGE extent, corresponding with less sub-epicardial (80% vs 95%, p=0.058) and more mid-wall LGE pattern (45% vs 14%, p=0.008) compared with non-STE patients. InvT patients had lower LVEF (52±12% vs 57±7%, p=0.029), and more transmural LGE pattern (32% vs 10%, p= 0.032) compared with non-invT patients. LGE distribution was similar whatever the presence of STE or non-invT (Table III).
Spatial correspondence between LGE areas and ECG findings was 35% for STE and 29% for invT (Figure 3).
3.2. Follow-up: CMR findings and correlation with STE and invT
FU CMR was performed after 100 [IQR 91; 125] days. T2 weighted hypersignal persisted in 7 patients (11%). As T0 CMR, sub-epicardial LGE pattern was the most prevalent and affected 55 patients (89%) and LGE was more often depicted in inferior and lateral territories, respectively, 66% (n=41) and 77% (n=48). There was a significant decrease in LVEF (p<0.0001), LVEDVI (p=0.034), LVESVI (p<0.0001), LVMI(p<0.0001) and LGE extent (p<0.0001). It’s the same for T2-weighted hypersignal (p<0.0001).
Time between FU ECG and FU CMR was 51 [IQR 27; 86] days. InvT patients presented similar data with lower LVEF (55±7% vs 59±4%, p=0.009) and a trend towards predominant transmural LGE (20% vs 4%, p=0.057). InvT was associated with higher LVMI (60±11 g/m2 vs 52±9 g/m2, p=0.023) and greater LGE extent (11±11g vs 5±5g, p=0.002) (Table III).
Spatial correspondence between LGE areas and ECG findings was 3% for STE and 18% for invT (Figure 3).
Follow-up
4.1. Normal FU ECG and changes in CMR parameters
13 There was no relation between normal FU ECG and changes in LVEF and LGE extent or indexed left ventricular volumes and mass in follow-up (Table IV). Nevertheless, patients with normal FU ECG had higher LVEF (60±4% vs 56±7%, p=0.011), lower LVEDVI (88±14 ml/m2 vs 98±21 ml/m2, p=0.031), lower LVESVI (36±7 ml/m2 vs 43±14 ml/m2, p=0.004) and lower LGE extent (4±5 g vs 8±9 g, p=0.028) compared with abnormal FU ECG.