Long-term imaging analysis of a myocarditis case: Utilizing strain with echocardiography and cardiovascular magnetic resonance findings

Abstract

Herein, we report a case of myocarditis in a 27-year-old male with long-term follow-up using longitudinal peak systolic strain (LPSS) measurements with transthoracic echocardiography (TTE) and late gadolinium enhancement (LGE) in cardiovascular magnetic resonance imaging (CMR). On admission, a predominant decrease was observed in the LPSS in the posterolateral segments of the TTE. After a period of two weeks, the values of the LPSS observed in the posterolateral segments were still slightly reduced, which is consistent with the LGE results in CMR. After a duration of 16 months, an improvement was noted in the LPSS and LGE results in all the segments. Moreover, a time-phase discrepancy was observed in the segmental longitudinal strain curve for a period of two weeks from the onset of myocarditis. However, an improvement in the discrepancy was detected after 16 months.

Learning objective

Longitudinal peak systolic strain (LPSS) on transthoracic echocardiography (TTE) has predominantly focused on diagnosing the acute phase of myocarditis. Herein, LPSS was evaluated not only in the acute phase but also in the chronic phase. Furthermore, the relationship between the results of segmental LPSS and late gadolinium enhancement was documented. We would like to emphasize the usefulness of LPSS on TTE both for identifying myocarditis and as a tool for the long-term follow-up of patients.

Introduction

Strain analysis using magnetic resonance imaging (MRI) has been reported to be useful in determining the prognosis of myocarditis [1], and strain imaging using echocardiography has been suggested to be a novel noninvasive tool for identifying myocarditis [[2], [3], [4]]. However, strain analysis, including measurements of segmental longitudinal peak systolic strain (LPSS) and global longitudinal strain (GLS), using transthoracic echocardiography (TTE) has predominantly focused on diagnosing the acute phase of myocarditis. Furthermore, only a few studies have evaluated the association between segmental LPSS and late gadolinium enhancement (LGE) using cardiovascular magnetic resonance imaging (CMR) [[2], [3], [4]].

We report a case of myocarditis evaluated through segmental LPSS, segmental longitudinal strain curve, and GLS using TTE from the acute to the chronic phase, and also, through LGE in CMR.

Case report

A 27-year-old man with no relevant medical and family history made a visit to our hospital with chief complaints of shortness of breath on exertion and palpitations, which he had experienced for 3 days prior to the hospital visit. On admission, his temperature was 37.2 °C, heart rate was 98 beats/min, and blood pressure was 120/82 mmHg. No evident heart murmurs, wheezing, or lower leg edema were observed.

An electrocardiogram (ECG) test performed on the patient revealed ST-segment elevation in all the leads, excluding the leads aVR, aVL, and V1 (Fig. 1A). An X-ray of the patient's chest revealed a cardiothoracic ratio of 46 %. Blood tests were performed, and they showed elevated levels of high-sensitivity troponin T (hsTnT) (0.656 ng/mL), N-terminal pro-brain natriuretic peptide (2455 pg/mL), creatine kinase (CK)-MB (20.1 IU/L), with white blood cell (6500/μL), C-reactive protein (0.20 mg/dL), aspartate aminotransferase (40 U/L), alanine aminotransferase (37 U/L), and creatinine (0.66 mg/dL). In the evaluation of collagen disease, serological assays, including those for antinuclear antibodies, yielded negative results. TTE was performed using the GE Vivid E95 system (General Electric Vingmed, Horton, Norway). The TTE revealed diffuse hypokinesis (ejection fraction: EF 40 %), dyssynchrony, and pericardial effusion (Fig. 1B, C, D and Video 1), while there was no evidence of mitral valve regurgitation. The tricuspid regurgitant pressure gradient was observed to be within normal limits (11 mmHg). The pulsed Doppler indices showed a decrease in several parameters, including early diastolic mitral flow velocity (E wave), late diastolic mitral flow velocity (A wave), early diastolic lateral annular velocity (e’ lateral), and early diastolic septal annular velocity (e’ septal) (Table 1).

Fig. 1.

(A) An electrocardiogram (ECG) showing ST-segment elevation in all leads, excluding the leads aVR, aVL, and V1 on admission. After two weeks, the ECG exhibits a negative T wave for the leads V3 to V6 and ST-segment elevation in all the leads, except in the leads aVR, aVL, and V1. The ECG demonstrates normal behavior after 16 months. (B, C) The transthoracic echocardiogram displays diffuse hypokinesis and edematous left ventricular hypertrophy, except in the septal and anteroseptal walls, and diffuse pericardial effusion (white arrows) is observed. (D) The ejection fraction decreases to 40 %, and dyssynchrony (yellow arrows).

RV, right ventricle; LV, left ventricle; LA, left atrial; Ao, aorta.

Table 1.

Results of transthoracic echocardiography.

	Onset	Two weeks later	Sixteen months later
GLS (%) (normal reference range − 22.8 ± 2.2 %) [7]	−9.9	−17.0	−18.3
EF (%)	40	65	60
IVST/PWT (mm)	8/8	7/7	7/7
LVDd/Ds (mm)	47/36	51/33	50/34
E wave (cm/s) (normal reference range 77 ± 15 cm/s) [6]	40	67	67
A wave (cm/s) (normal reference range 40 ± 10 cm/s) [6]	25	25	33
E/A ratio	1.6	2.6	2.0
Dct (ms)	187	176	156
LA reservoir strain (%) (normal reference range 49.7 ± 7.9 %) [7]	24.4	34.5	44.6
e’ lateral/septal (cm/s)	6.5/9.8	16.7/14.3	20.3/12.8

At the onset, reductions in global longitudinal strain (GLS), ejection fraction (EF), and early diastolic annular velocity (e’) are evident. The ratio of the early (E wave) to late (A wave) diastolic filling velocities (E/A) is within the normal range; however, the individual velocities of both the E wave and A wave are decreased. The left atrium (LA) reservoir strain through speckle-tracking echocardiography is at a low value. Two weeks later, the GLS shows insufficient recovery. While the E wave velocity has increased, the A wave velocity remains low. The LA reservoir strain shows improvement; however, the value remains low. At 16 months, the GLS remains low, but other parameters have recovered.

GLS, global longitudinal strain; EF, ejection fraction; IVST, interventricular septum thickness; PWT, posterior left ventricular wall thickness; LVDd, left ventricular end-diastolic diameter; LVDs, left ventricular end-systolic diameter; E, early diastolic mitral flow velocity; A, late diastolic mitral flow velocity; E/A, the ratio of early to late diastolic velocities; LA, left atrium; Dct, deceleration time of early diastolic mitral flow velocity; e’ lateral, early diastolic lateral annular velocity; e’ septal, early diastolic septal annular velocity.

The LPSS measurements using speckle-tracking echocardiography were analyzed using Tomtec Imaging Systems (Unterschleissheim, Germany). The LPSS demonstrated a predominant decrease in the posterior lateral segment, and the GLS and left atrium reservoir strain (LA strain) were markedly reduced by −9.9 % and 24.4 %, respectively (Fig. 2C, Table 1). A time-phase discrepancy was observed in the peaks of each segment (Fig. 2F).

Fig. 2.

Follow-up of myocarditis: Evaluating changes using transthoracic echocardiogram (TTE), cardiovascular magnetic resonance imaging (CMR), and strain analysis. (A) CMR showed late gadolinium enhancement (LGE) in the posterior lateral and septal segments (represented by white arrows). (B) After 16 months, these findings demonstrate an improvement. (C) On admission, the longitudinal peak systolic strain (LPSS) measurement using TTE exhibits a predominant decrease in the posterolateral and septal segments (represented by yellow arrows). (D) Two weeks later, the LPSS reduction persisted in the posterolateral and septal regions, similar to CMR (represented by white arrows). (E) After 16 months, these findings demonstrate improvement. (F, G, H) The values of longitudinal strain (plotted on the vertical axis) and time (plotted on the horizontal axis) for each segment are demonstrated in the 3ch view obtained by TTE. (F) On admission, a decrease in the values of longitudinal strain (vertical) is observed in all the segments, and a discrepancy is noted in the peaks of each segment (double-headed arrow). (G) After two weeks, an improvement is observed in the values of longitudinal strain (vertical). However, the peaks of discrepancy are still present for each segment (double-headed arrow); (H) 16 months later, an improvement in the discrepancy is noted for all the segments (double-headed arrow). The global longitudinal strain, ejection fraction, and pulsed Doppler indices demonstrate an improvement over time after myocarditis.

RV, right ventricle; LV, left ventricle; ECG, electrocardiogram.

Emergency coronary angiography was performed, which revealed the absence of coronary artery stenosis, and hence, right ventricle myocardial biopsy was performed. Myocardial biopsy showed no results that were suggestive of myocarditis-like infiltration with lymphocytes and eosinophils. The results also did not reveal any granulomatous lesions related to sarcoidosis. The following medicines were administered to the patient: furosemide (20 mg/day), bisoprolol (1.25 mg/day), enalapril (2.5 mg/day), colchicine (0.5 mg/day), and heparin (10,000 units/day). During hospitalization, the patient exhibited no heart failure exacerbations or life-threatening arrhythmias.

After a period of two weeks, CMR demonstrated posterolateral and septal segments with a high signal intensity in T2-weighted imaging and LGE images using T1-based imaging (Fig. 2A), which is consistent with the findings of the segmental LPSS measurements (Fig. 2D). The diagnosis of myocarditis was performed based on Lake Louise Criteria II (positive findings in both T1- and T2-based images on cardiac MRI) and the criteria of Centers for Disease Control and Prevention. The diagnosis was done by using the ECG, TTE, CMR changes, and elevated CK and hsTnT values with chest pain [5]. The EF increased from 40 % to 65 %, and the edematous left ventricular hypertrophy and pericardial effusion were nearly resolved as observed by TTE after a period of two weeks (Video 2). The GLS also demonstrated an improvement from −9.9 % to −17.0 % but exhibited a low value of LPSS in the posterolateral and septal segments (Fig. 2D, Table 1). A time-phase discrepancy was still present for each segment (Fig. 2G). After a period of 16 months, LGE by CMR and LPSS and a time-phase discrepancy on the TTE results were normalized in all the segments (Fig. 2B, E, H and Video 3). Although the GLS was low for the age of the patient [7], the LA reservoir strain and A wave were also normalized (Table 1).

Discussion

In this case of myocarditis, we demonstrated long-term follow-up through strain analysis, including measurements of segmental LPSS and GLS using TTE. Furthermore, the relationship between the reduced LPSS segments obtained using the TTE and LGE segments through CMR was documented (Fig. 2A, B, D, E). This observation is consistent with the results in previous reports [3,4]. Uppu et al. had reported a moderate correlation (r = 0.68) between the overall number of the reduced LPSS segments and LGE segments per patient [3].

Two weeks later, it was observed that while the EF had normalized, both the LPSS and GLS remained abnormal [7]. These are indicators of sensitive long-axis myocardial contractile function, suggesting that they are complementary to EF [1]. Moreover, two weeks later, the E/A ratio demonstrated a higher value. This is likely due to improved compliance in the left ventricle and the recovery of peak E velocity, as shown by the changes in pericardial effusion, myocardial edema, and e' lateral/septal values. However, as the peak A velocity remained low, it resulted in an increased E/A ratio. This interpretation is supported by the consistently low value of the LA reservoir strain in Table 1 [7], indicating impaired left atrial function and suggesting that even after two weeks, there was no improvement in the peak A velocity. In recent studies on myocarditis, decreases have been observed both in GLS and LA strain. Notably LA strain is emerging as a prognostic predictor [8,9].

At 16 months, the peak A velocity had also recovered, possibly linked to improved LA function, as seen in the simultaneous increase in the LA reservoir strain in Table 1. It has been suggested that by performing strain analysis, such as LA reservoir strain, GLS, and LPSS, in conjunction with the absolute values of peak E and A velocity, it is possible to evaluate the entire left cardiac system, including the LA [9].

This patient's condition normalized with an EF returning to normal within two weeks, and he was discharged without ventricular tachycardia (VT) or ventricular fibrillation (VF). Recent Japanese registry studies on fulminant myocarditis have indicated that older age, non-sinus rhythm, low left ventricular wall motion (<40 %), and the presence of VT/VF on admission day are associated with a worse 90-day survival [10]. This patient, who presented with an EF of 40 % upon admission, was young and did not experience VT/VF or other severe complications. This suggests a lower risk of deterioration and minimal myocardial damage, likely contributing to their early recovery. Furthermore, recent research has suggested a link between interleukin (IL)-6 and myocarditis [11], and colchicine inhibits IL-6 production, which is derived from IL-1β [12]. In this case, the patient received colchicine treatment, which may have played a role in the successful outcome [13].

Long-term observation has allowed us to witness the recovery process of myocarditis based on the coincidence of time phases. Takamura et al. reported that mechanical dyssynchrony also improved with the recovery of myocarditis [14]. The phase discrepancy, as illustrated in Fig. 2F, G, and H, enhances the clarity of myocardial dyssynchrony. Similar to the bull's eye display in Fig. 2C, D, and E, we consider this method useful for conveying the progression of recovery during follow-up observations.

Therefore, our study suggests that strain analysis during the follow-up after myocarditis can provide important information on the recovery of the injured myocardium [15], and routine observation may help prevent adverse events. Although ultrasonography is noninvasive and has the advantage of being repeatable, it exhibits several limitations, including poor visualization and difficulties in evaluating segments for some patients. Moreover, the quality of ultrasound machines obtained from different companies varies despite high reproducibility [16].

In CMR, T1 mapping and extracellular volume (ECV) could improve the detection of LGE [2]. However, only limited facilities are available for the analysis of T1 mapping and ECV. Therefore, we believe that the values of the segmental LPSS obtained using TTE could also be useful for detecting LGE [3].

The following are the supplementary data related to this article.

Video 1

Echocardiography, parasternal long-axis view, and short-axis view, showing diffuse hypokinesis and dyssynchrony with an ejection fraction of 40 %; diffuse pericardial effusion is observed on admission.

Video 2

Echocardiography, parasternal long-axis view, and short-axis view, showing almost normal systolic function (an ejection fraction of 65 %) after two weeks. However, pericardial effusion persists.

Video 3

Echocardiography, parasternal long-axis view, and short-axis view, showing a sustained normal systolic function (an ejection fraction of 60 %) and the complete resolution of pericardial fluid after 16 months.

Patient consent statement

Written informed consent was obtained from the patient for publication of the case and accompanying images.

Declaration of competing interest

None declared.