ARTICLE

Vol. 137 No. 1607 |

DOI: 10.26635/6965.6704

Favourable outcome of acute myocarditis diagnosed by cardiac magnetic resonance imaging

Acute myocarditis (AM) is a clinically challenging entity characterised by a wide spectrum of presentation—ranging from no symptoms to fulminant heart failure—and it can also present in a similar fashion to acute coronary syndrome.

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Acute myocarditis (AM) is a clinically challenging entity characterised by a wide spectrum of presentation—ranging from no symptoms to fulminant heart failure—and it can also present in a similar fashion to acute coronary syndrome. Historically, endomyocardial biopsy (EMB) was the only diagnostic test available, and it remains the diagnostic gold standard, but utilisation of this test is limited by its invasive nature, complication rates and low sensitivity. The availability of cardiac magnetic resonance imaging (cMRI) provides an alternative, non-invasive method of myocardial tissue characterisation and has been applied with high diagnostic accuracy in AM.1 In addition to diagnostic utility, cMRI also provides unique prognostic information in AM, where the pattern of late gadolinium enhancement has been shown to predict subsequent major adverse cardiovascular events.2,3

Previous studies on clinical presentation and survival following AM have focussed on EMB-proven cases, but these are limited by selection bias where only severe cases would warrant biopsy.4,5 Furthermore, cMRI is now increasingly utilised for patients presenting with myocardial infarction with non-obstructive coronary arteries (MINOCA), and up to 37% of these patients are found to have AM when cMRI is used.6 Patriki et al. systematically screened all patients presenting with MINOCA with cMRI and concluded that the incidence of AM is 0.63 per 1,000 of all hospital admissions. This is one of the few existing estimates of the true incidence of AM in the general population.7

As the availability and uptake of cMRI increases, it follows that more cases of AM may be diagnosed, and this may represent a lower risk group compared to previously described populations. The aim of this study is to review the clinical features and natural history of cMRI-diagnosed AM, and to assess the inpatient and medium-term outcome of this patient group.

Materials and methods

Patient selection

All patients undergoing cMRI at Te Whatu Ora – Health New Zealand Te Toka Tumai Auckland (formerly Auckland District Health Board) for any indication between 1 July 2012 and 30 June 2022 were retrospectively identified. Consecutive patients with a final diagnosis of AM based on cMRI imaging criteria and on clinical grounds were included. This study received institutional approval for falling within recommended research methodologies defined by the New Zealand Health and Disability Ethics Committees’ standard operating procedures.

Data collection and definitions

All data were retrieved from electronic medical records. Baseline demographics, clinical features, in-hospital complications, long-term outcome measures and vital status were recorded. Follow-up was until 1 January 2023 or until the last documented healthcare encounter for patients who left the region. We recorded important clinical outcomes including the occurrence of ventricular arrhythmia during the index admission, cardiac ablation procedure, insertion of implantable cardioverter defibrillator (ICD), subsequent hospitalisation for heart failure, recurrent or chronic myocarditis, cardiac transplantation and death. Ventricular arrhythmia included ventricular fibrillation (VF) or ventricular tachycardia (VT) (more than 4 beats). Continuous variables were reported as mean with standard deviation or median with interquartile range. Categorical variables were reported in absolute values with percentages.

cMRI protocol and imaging criteria

All scans were performed on 1.5T (Avanto, Siemens, Germany) or 3T (Skyra, Siemens, Germany) magnets. Standard imaging sequences to assess left ventricle (LV) volumes, mass and function (SSFP) as well myocardial oedema (T2 weighted imaging) and late gadolinium enhancement as per Society for Cardiovascular Magnetic Resonance guidelines were performed.8 Gadolinium contrast was administered at a dose of 0.1mmol/kg. Diagnosis of myocarditis on cMRI was based on the Lake Louise criteria.9

Results

A total of 196 cases of AM were identified, and there was a gradual increase in the number of cases diagnosed over time (Figure 1). The mean age at index presentation was 42 years, and 155 (79%) were male (Table 1). The most common presenting symptom was chest pain, which was present in 157 patients (80%), followed by fever or a viral prodrome in 95 patients (48%) and dyspnoea in 52 patients (27%) respectively. One patient presented with resuscitated cardiac arrest. ST-segment elevation was present in 64 patients (33%), coronary angiography was undertaken in 117 patients (60%), and none had obstructive coronary artery disease. EMB was undertaken in 10 patients, of which six revealed normal findings.

On cMRI, mean left ventricular ejection fraction (LVEF) was 56%, and in nine patients it was <40% (Table 2). Other common findings included wall motion abnormality in 78 patients (40%) and pericardial effusion in 50 patients (26%). Late gadolinium enhancement was observed in the majority (89%), and this was most commonly seen in the basal inferior and inferolateral segments, with a predominant mid-wall and subepicardial distribution.

Most patients had a benign in-hospital course, and the median length of stay was 4 days. Arrhythmias were the most common event, occurring in 24 patients (12%), which was primarily due to VT. Acute kidney injury occurred in 19 patients (10%) during the index admission. Five patients required admission to intensive care, and one had cardiogenic shock requiring veno-arterial extracorporeal membrane oxygenation, acute dialysis and a prolonged recovery period.

We observed two cases of presumed COVID-related AM and nine cases of presumed COVID-19 vaccine (Pfizer) related AM. This latter group consisted of seven males and two females, mean age 27 (±13) years. One case occurred after the first vaccination, seven after the second and one after the third vaccination. The median time from vaccination to presentation to hospital was 3 days. All of these patients had normal LVEF. One patient had inpatient ventricular arrhythmia, but there were no other important cardiac events either during the index hospitalisation or at follow-up (median 1.2 years) (Table 3).

Immunosuppression was used in 22 patients (11%), consisting of prednisone alone in 13 patients (7%) and other immunosuppressive agents in the remaining nine patients (5%), which included methylprednisolone, intravenous immunoglobulins, sirolimus, leflunomide, mycophenolate, tocilizumab and cyclophosphamide. The indication for immunosuppression was usually severe left ventricular impairment or a coexisting underlying autoimmune disorder.

All patients survived the index admission, and after a median follow-up of 4.6 years there were no cardiac-related deaths, but three patients died from advanced malignancy. Important cardiac events included recurrent or chronic myocarditis in 15 patients (8%), with a median time to recurrence of 2 years. ICD insertion was done in five patients (3%), one during the index admission and four following discharge, all for the indication of recurrent VT. Three patients were readmitted for heart failure after 16, 17 and 31 months, and one patient received a cardiac transplant for giant cell myocarditis. Two patients underwent cardiac ablation procedure for recurrent VT and multifocal ventricular ectopy with VT, respectively.

View Figure 1, Table 1–3.

Discussion

Our results demonstrate the favourable clinical course and medium-term prognosis of patients with AM that is diagnosed by cMRI. This is in keeping with findings of previous cMRI studies, which have reported short- and medium-term mortality rates of 0–3.5%.2,10 In contrast, Grün et al. examined 203 cases of EMB-proven myocarditis (45% of patients presenting with New York Heart Association [NYHA] III or IV symptoms) and reported a mortality rate of 19.2% at 4.7 years. This highlights the spectrum of disease severity seen with AM. Further, these studies support the notion that patients who are determined to be clinically suitable for cMRI tend to have milder manifestations of the disease, and this underlies the need to define biomarkers that identify a “lower risk” cohort who can be reassured without follow-up surveillance imaging.11

We observed few serious in-hospital complications of AM in this study. Importantly, all patients survived the index admission, and only five required intensive care. VT was the most frequently observed event, and it occurred in 16 patients. Chopra et al. found that the occurrence of VT was more commonly observed in patients that presented in a pseudo-infarct manner of AM (i.e., when the clinical presentation mimics acute coronary syndrome), and this subset of patients had a higher cumulative event rate at follow-up than those that did not present in a pseudo-infarct manner.2 Similarly, the presence and extent of late gadolinium enhancement is recognised to be an important prognostic factor in AM, where it is estimated to be associated with a >3-fold increased risk of adverse cardiac outcomes compared to those that do not have late gadolinium enhancement.12

Although the majority of patients in our study presented with mild disease, immunosuppression was used in 22 patients, mostly in the form of corticosteroids. Further, VT occurred in five of these 22 patients and VF occurred in one, which is likely consequent to the more aggressive and active nature of their disease. We observed one case of a patient who developed autoimmune myocarditis due to a novel monoclonal antibody (nivolumab). This patient was treated with intravenous methylprednisolone and intravenous immunoglobulins, as well as a tapering course of oral corticosteroid; however, he eventually died from advanced malignancy. Autoimmune myocarditis is an emerging category of AM and is seen in patients treated with novel immune checkpoint inhibitors. This group of patients can only be expected to grow as the indications for and uptake of these drugs increase, and clinicians should have a high index of suspicion of this adverse effect in the cardio-oncology patient group.13

Further, we observed cases of presumed COVID-19 vaccine–related AM, and this entity has received considerable research and public interest. Though it is a very uncommon occurrence, estimated at 1.08 per 100,000 in one nation-wide study, a subset of these patients manifest severe cardiac impairment and require advanced therapies including cardiac transplantation.14 In our current study, all patients had uneventful outcomes; however, these cases likely represent only a small subset of patients with mild clinical manifestations.

Appropriate follow-up after hospital discharge remains an unclear aspect in the management of patients with AM. Importantly, while most patients can expect recovery, some develop chronic myocarditis or progress to dilated cardiomyopathy.15 The European Society of Cardiology guidelines advise “long-term non-invasive cardiological follow-up” after normalisation of cardiac enzymes;16 however, several studies have demonstrated a lack of correlation between cardiac enzyme release and clinical outcomes in AM, and a novel implementation of cMRI in AM demonstrated persistent abnormal myocardial tissue processes (including late gadolinium enhancement) despite normalisation of cardiac enzymes and inflammatory parameters.17 On the other hand, absence of late gadolinium enhancement in AM is a powerful predictor of cardiovascular survival,11 which has resulted in the suggestion that convalescent cMRI could form part of the short-term follow-up of these patients regardless of cardiac enzyme level.

Limitations

This study is retrospective and from a single centre, and thus is subject to the usual limitations of this design. Second, although cMRI has very high diagnostic accuracy for AM, it is possible that some included cases reflected alternative aetiologies as the gold standard test of EMB was not performed in the majority of patients. Last, we included all aetiologies of AM, which may be a heterogenous group, each with its own risk of complications and natural history.

Conclusion

Patients with mild forms of AM diagnosed by cMRI have a favourable in-hospital clinical course and medium-term prognosis. Clinicians should have a low index of suspicion for AM in patients presenting with supporting clinical features, and cMRI should be considered early in the work-up process, particularly in those presenting with MINOCA.

Aim

Acute myocarditis (AM) is increasingly diagnosed in the era of more sensitive imaging techniques. The natural history of AM diagnosed on cardiac magnetic resonance imaging (cMRI) may be different to historic cohorts due to the detection of milder disease. This study aims to measure the outcome of patients with AM detected by cMRI.

Methods

We retrospectively reviewed all cMRI studies performed over a 10-year period between 2012 and 2022. Patients with a diagnosis of AM based on cMRI criteria and clinical assessment were selected for inclusion.

Results

One hundred and ninety-six patients were included. The mean age was 42 years and 79% were male. Chest pain, fever or viral prodrome and dyspnoea were the most common presenting symptoms, and one patient presented with cardiac arrest. On cMRI, nine patients had left ventricular ejection fraction <40% and 174 patients had evidence of late gadolinium enhancement, most commonly affecting the basal inferolateral and inferior segments in a subepicardial and mid-wall distribution. Five patients required admission to the intensive care unit (ICU). Important outcomes included the occurrence of ventricular arrhythmias in 17, recurrent or chronic myocarditis in 15 and implantable cardioverter defibrillator insertion in five patients, respectively. After a median follow-up of 4.6 years, there were no cardiac-related deaths, and three patients died from malignancy-related causes.

Conclusion

Patients with AM diagnosed by cMRI have a favourable medium-term outcome. Severe left ventricular dysfunction and ICU admission are rare. cMRI should be considered early in patients with suspected AM.

Authors

Sophie Rees, MBChB: Registrar, Health New Zealand – Te Whatu Ora, General Medicine Department, Middlemore Hospital, Hospital Road, Otahuhu, Auckland, New Zealand.

Ammar Alsamarrai, MBChB: Cardiology Registrar, Health New Zealand – Te Whatu Ora, Green Lane Cardiovascular Services, Auckland City Hospital, Auckland, New Zealand.

Jessica Fulton, MBChB: Registrar, Health New Zealand – Te Whatu Ora, General Medicine Department, Middlemore Hospital, Hospital Road, Otahuhu, Auckland, New Zealand.

Jithendra B Somaratne, FRACP PhD: Consultant Cardiologist, Health New Zealand – Te Whatu Ora, Green Lane Cardiovascular Services, Auckland City Hospital, Auckland, New Zealand.

Correspondence

Sophie Rees, MBChB: Registrar, Health New Zealand – Te Whatu Ora, General Medicine Department, Middlemore Hospital, Hospital Road, Otahuhu, Auckland, New Zealand.

Correspondence email

sophierees6@gmail.com

Competing interests

The authors have no conflict of interests to declare.

1)       Kotanidis CP, Bazmpani MA, Haidich AB, et al. Diagnostic Accuracy of Cardiovascular Magnetic Resonance in Acute Myocarditis: A Systematic Review and Meta-Analysis. JACC Cardiovasc Imaging. 2018;11(11):1583-90. doi: 10.1016/j.jcmg.2017.12.008.

2)       Chopra H, Arangalage D, Bouleti C, et al. Prognostic value of the infarct- and non-infarct like patterns and cardiovascular magnetic resonance parameters on long-term outcome of patients after acute myocarditis. Int J Cardiol. 2016;212:63-9. doi: 10.1016/j.ijcard.2016.03.004.

3)       Gräni C, Eichhorn C, Bière L, et al. Prognostic Value of Cardiac Magnetic Resonance Tissue Characterization in risk Stratifying Patients With Suspected Myocarditis. J Am Coll Cardiol. 2017;70(16):1964-76. doi: 10.1016/j.jacc.2017.08.050. Erratum in: J Am Coll Cardiol. 2017 Nov 28;70(21):2736. doi: 10.1016/j.jacc.2017.10.042. 

4)       McCarthy RE 3rd, Boehmer JP, Hruban RH, et al. Long-term outcome of fulminant myocarditis as compared with acute (nonfulminant) myocarditis. N Engl J Med. 2000;342(10):690-5. doi: 10.1056/NEJM200003093421003.

5)       Ammirati E, Veronese G, Brambatti M, et al. Fulminant Versus Acute Nonfulminant Myocarditis in Patients With Left Ventricular Systolic Dysfunction. J Am Coll Cardiol. 2019;74(3):299-311. doi: 10.1016/j.jacc.2019.04.063.

6)       Pathik B, Raman B, Mohd Amin NH, et al. Troponin-positive chest pain with unobstructed coronary arteries: incremental diagnostic value of cardiovascular magnetic resonance imaging. Eur Heart J Cardiovasc Imaging. 2016;17(10):1146-52. doi: 10.1093/ehjci/jev289. 

7)       Heidecker B, Ruedi G, Baltensperger N, et al. Systematic use of cardiac magnetic resonance imaging in MINOCA led to a five-fold increase in the detection rate of myocarditis: a retrospective study. Swiss Med Wkly. 2019;149:w20098. doi: 10.4414/smw.2019.20098.

8)       Kramer CM, Barkhausen J, Bucciarelli-Ducci C, et al. Standardized cardiovascular magnetic resonance imaging (CMR) protocols: 2020 update. J Cardiovasc Magn Reson. 2020;22(1):17. doi: 10.1186/s12968-020-00607-1.

9)       Friedrich MG, Sechtem U, Schulz-Menger J, et al. Cardiovascular magnetic resonance in myocarditis: A JACC White Paper. J Am Coll Cardiol. 2009;53(17):1475-87. doi: 10.1016/j.jacc.2009.02.007.

10)    Sanguineti F, Garot P, Mana M, et al. Cardiovascular magnetic resonance predictors of clinical outcome in patients with suspected acute myocarditis. J Cardiovasc Magn Reson. 2015;17(1):78. doi: 10.1186/s12968-015-0185-2.

11)    Grün S, Schumm J, Greulich S, et al. Long-term follow-up of biopsy-proven viral myocarditis: predictors of mortality and incomplete recovery. J Am Coll Cardiol. 2012;59(18):1604-15. doi: 10.1016/j.jacc.2012.01.007.

12)    Georgiopoulos G, Figliozzi S, Sanguineti F, et al. Prognostic Impact of Late Gadolinium Enhancement by Cardiovascular Magnetic Resonance in Myocarditis: A Systematic Review and Meta-Analysis. Circ Cardiovasc Imaging. 2021;14(1):e011492. doi: 10.1161/CIRCIMAGING.120.011492.

13)    Mahmood SS, Fradley MG, Cohen JV, et al. Myocarditis in Patients Treated With Immune Checkpoint Inhibitors. J Am Coll Cardiol. 2018;71(16):1755-64. doi: 10.1016/j.jacc.2018.02.037.

14)    Cho JY, Kim KH, Lee N, et al. COVID-19 vaccination-related myocarditis: a Korean nationwide study. Eur Heart J. 2023;44(24):2234-43. doi: 10.1093/eurheartj/ehad339.

15)    Kindermann I, Barth C, Mahfoud F, et al. Update on myocarditis. J Am Coll Cardiol. 2012;59(9):779-92. doi: 10.1016/j.jacc.2011.09.074.

16)    Caforio AL, Pankuweit S, Arbustini E, et al. Current state of knowledge on aetiology, diagnosis, management, and therapy of myocarditis: a position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases. Eur Heart J. 2013;34(33):2636-48,  2648a-2648d. doi: 10.1093/eurheartj/eht210.

17)    Berg J, Kottwitz J, Baltensperger N, et al. Cardiac Magnetic Resonance Imaging in Myocarditis Reveals Persistent Disease Activity Despite Normalization of Cardiac Enzymes and Inflammatory Parameters at 3-Month Follow-Up. Circ Heart Fail. 2017;10(11):e004262. doi: 10.1161/CIRCHEARTFAILURE.117.004262.