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REVIEW ARTICLE
Year : 2021 | Volume
: 10
| Issue : 4 | Page : 101-105
A review on myocarditis with preserved ejection fraction: Diagnosis and treatment
Nasim Naderi1, Sepideh Jafari Naeini2, Zahra Hosseini1
1 Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences Tehran, IR Iran
2 Cardiovascular Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Correspondence Address:
Dr. Sepideh Jafari Naeini
Cardiovascular Research Center, Shahid Beheshti University of Medical Sciences, Tehran
Iran
Source of Support: None, Conflict of Interest: None
DOI: 10.4103/rcm.rcm_40_21
Myocarditis with preserved ejection fraction (MCpEF) is a subgroup of myocarditis with normal or near-normal left ventricular systolic function. Its prevalence has been reported to be low, and there are limited data about the diagnostic strategy, management, and outcome. Initial manifestation of myocarditis can be new-onset heart failure, acute coronary syndrome-like presentation, life-threatening arrhythmia, or even sudden cardiac death. Echocardiography with two-dimensional speckle-tracking mode and cardiac magnetic resonance imaging have pivotal roles in diagnosis and management of the disease. The present study is based on a research on “myocarditis preserved ejection fraction (EF)” or “ myocarditis with normal EF” mainly in PubMed, Google Scholar, and Embase databases. The search focused on the aspects of the disease which is not usually mentioned clearly. In contrast to the myocarditis as a general concept, the total number of clinical studies or case reports in the context of myocarditis with preserved EF is really low. Most treatment strategies have been based on the patient's initial presentation, and there are not enough clinical trials or long-term follow-up studies to confirm the most accurate diagnostic and therapeutic approach. In conclusion, although MCpEF has been known as a subgroup of myocarditis with specific clinical and imaging features, there are still a lot of questions about the diagnosis, management strategy, and patient prognosis which require further studies to be investigated.
Keywords: Echocardiography, magnetic resonance imaging, myocarditis
Myocarditis has been a neglected cause of unexplained cardiomyopathy in 10%–17% of patients based on endomyocardial biopsy (EMB) results.[1] The prevalence of myocarditis with preserved left ventricular ejection fraction (LVEF) has been around 3–6 per 100,000 population in 2011[2] and it has been estimated that up to 30% of patients affected by chronic myocarditis have preserved LVEF.[3] Definition of preserved ejection fraction (EF) has not been the same in different studies; in most of them, LVEF more than 45% or 50% is considered.
A wide variety of clinical presentations (such as new-onset heart failure, life-threatening arrhythmia, and sudden cardiac death) makes myocarditis a challenging diagnosis, especially when it mimics acute coronary syndrome (ACS) as the first presentation (pseudo-infarct pattern or variant angina) and needs high clinical suspicion.[4],[5],[6] Myocarditis with preserved ejection fraction (MCpEF) is usually made by a focal inflammation in the myocardium and can be manifested by chest pain or even by supraventricular arrhythmias.[1],[7] More than 50 cardiotropic viruses are identified which can lead to viral infection as the most common cause of myocarditis.[5]
There is a little evidence about the presentation, preferred diagnostic methods, and treatment approaches in this type of myocarditis. This review explains different aspects of the diagnosis and treatment of MCpEF with special focus on the aspects which are different from myocarditis with reduced EF.
Evidence AcquisitionThe present study is based on comprehensive research in May 2021 with the keywords: “myocarditis preserved EF” or “myocarditis with normal EF” with an overview of relevant “myocarditis” papers in PubMed, Google Scholar, and Embase databases.
The search included case reports, case–control studies, review articles, observational studies, and randomized clinical trials and focused on the details which are not usually mentioned clearly, such as diagnostic approach, therapeutic options, imaging modalities, and the role of defibrillator devices. After exclusion of duplicated researches and irrelevant topics, 40 papers out of 180 are finally selected for this review article.
ResultsDiagnostic approach
Role of coronary angiography
Although frequent use of coronary angiography in focal myocarditis is reported, it depends on clinical t and may be deferred if there are not any relevant risk factors for coronary artery disease (CAD) in the presence of acute chest pain or when the patient is too young, and the probability of the presence of CAD is not high.[7]
Role of cardiac imaging
Although cardiac magnetic resonance imaging (MRI) is a valuable noninvasive method, its use may be limited due to loss of widespread availability and high cost.[7]
Earlier studies mostly demonstrated the importance of late gadolinium enhancement (LGE) pattern in subsequent clinical outcomes even in LVEF more than 50%. Although subepicardial enhancement in inferior or lateral wall has been a frequent pattern of LGE in myocarditis, delayed enhancement (DE) in midwall and anteroseptal wall has been associated with lower LVEF and more cardiac remodeling. Anteroseptal LGE has also been associated with greater level of troponin and higher left ventricular end-diastolic volume index.[8] Complementary MRI techniques such as T1 and T2 mapping have been reported to be more effective than conventional methods for the diagnosis in the absence of typical findings such as LGE.[9]
It is valuable to remind that biopsy-proven myocarditis can be documented in cardiac wall segments that cardiac MRI did not show any LGE in favor of myocarditis.[10]
Transthoracic echocardiography (TTE) with two-dimensional speckle tracking has also been introduced as an alternative method for evaluating systolic dysfunction with lower cost and better availability in comparison with cardiac magnetic resonance (CMR) and also with higher sensitivity than conventional TTE.[7] It has been probably a superior method in contrast to Lake Louise criteria (LLC) (in CMR) for the detection of chronic MCpEF.[3] Abnormal global longitudinal strain (GLS) has been also detected in 58% of children with focal myocarditis and normal EF in favor of subclinical dysfunction.[11] According to a retrospective study by Chinali et al. in 2020, residual myocardial fibrosis in CMR prevents longitudinal strain to be normalized during follow-up.[11]
In 2010, Di Bella et al. reported a diffuse significant reduction in GLS in myocarditis even in the absence of epicardial LGE in CMR, but this impairment was more prominent in the segments with concomitant LGE in CMR study.[10] Study results were in favor of unaffected radial strain (irrespective of the presence of LGE) but impaired circumferential strain only in the concomitant presence of DE which involves more than 25% of right or left ventricular wall thickness.[10] Peak circumferential strain has been correlated well with LGE with prognostic significance.[12]
Although different studies introduced the evaluation of global circumferential strain as a useful diagnostic method for the diagnosis of MCpEF,[13],[14] Gatti et al. in 2019 investigated global radial, circumferential, and longitudinal strain peak (%) with systolic and diastolic strain rate and did not find any differences between MCpEF group and healthy volunteers except in left ventricular (LV) mass index and T1 and T2 mapping results.[15] This result is in contrast with Kotake et al. report in 2018 which was in favor of significant difference between LVGLS and LVGCS between the MCpEF and control group. This study also delineated the compatibility of reduced lateral LVGLS with the presence of LGE in lateral LV free wall.[16]
A cross-sectional study in 2019 on 50 patients with acute myocarditis with normal LVEF concluded that these patients have specific echocardiographic characteristics in comparison with the control group: higher LV volume, higher indexed LV mass, lower LV GLS, larger right ventricular (RV) diameter, reduced RV fractional area change, and reduced RV free wall GLS.[17]
LLC in cardiac MRI has been criticized in proper diagnosis of patients with suspected myocarditis. In recent years, complementary methods such as feature tracking (FT) imaging for evaluation of cardiac strain have been used as an adjunctive method.[18],[19] Khanji et al. in 2015 evaluated 33 patients suspected of myocarditis with LVEF more than %55. CMR FT parameters, three-dimensional peak LV strain, strain rate, and myocardial velocities have been evaluated in these patients, and the results were in favor of acceptable sensitivity of this method for predicting future changes in LVEF in the presence of normal baseline EF.[19]
An observational study on myocardial infarction (MI) with nonobstructive coronary arteries (MINOCA) revealed that the patients with normal EF myocarditis had higher levels of C-reactive protein in comparison with the patients with MI. In contrast to previous studies on reduced EF, this study concluded that LGE is not totally relevant to cardiac outcomes in the population study with preserved EF. Bière et al. study also explained that the risk of arrhythmic events is reported to be the same in both MI and myocarditis groups with preserved EF.[20] MI in the “Fourth Universal Definition of MI (2018)” is defined as an acute myocardial injury due to acute myocardial ischemia. Based on this definition, myocarditis subgroup would be omitted in future researches about MINOCA due to nonischemic etiology. Elevated level of troponin in this entity has been related to myocardial injury but not infarction.[21]
Similar studies on the echocardiographic features of acute myocarditis reported more sensitivity of GLS in contrast to the evaluation of LVEF for detecting subclinical LV systolic dysfunction. Lateral e'velocity has been introduced as a useful variable with 50% sensitivity and 84% specificity to detect acute myocarditis.[22]
Another echocardiographic feature in these patients is diastolic dysfunction which can lead to reduced peak exercise tolerance and peak ventricular filling in long-term follow-up.[22]
In a cohort study on biopsy-proven myocarditis, 49% of the study population with normal LVEF had symptomatic diastolic dysfunction on 6-year follow-up. The final study result was against the usual idea that there is a high probability of full recovery in these patients.[22] Abnormal findings such as increase in septal thickness and mass (pseudo-inflammatory pattern) in acute myocarditis may even last for more than 2 years.[23]
A review on two important subpopulations
Myocarditis in COVID-19
Since the initiation of COVID-19 pandemic, different reports about myocarditis due to COVID-19 infection have been established[24] which is usually diagnosed by global or regional wall motion abnormalities and reduced LVEF, arrhythmia, or even with unstable hemodynamic and cardiogenic shock.[24] Different mechanisms have been proposed such as cytokine release, cardiomyocyte damage, scar formation in myocardium, and microvascular disease.[24] MCpEF may also be diagnosed by cardiac MRI in the presence of high troponin levels, although there are different etiologies for elevated serum troponin in these patients.[24],[25]
Isolated right ventricular myocarditis
Isolated RV myocarditis is a rare cause of myocarditis in the presence of normal LV systolic function which can be diagnosed properly by cardiac MRI.[26] In severe cases, it can even lead to severe RV dysfunction and cardiogenic shock.[27] Diagnosis can be made by CMR or EMB. Treatment by supportive care or immunosuppressive therapy may be considered based on underlying etiology and presence of inflammatory infiltration or specific diagnosis in EMB.[28]
Treatment strategies
Medical follow-up
There is some evidence in favor of excellent prognosis in MCpEF in contrast to other types with LV systolic dysfunction or life-threatening arrhythmia.[1],[29] Rapid resolution of electrocardiographic and echocardiographic abnormalities in up to 6 months is expected in low-risk cases (ACS or supraventricular tachycardia presentation).[1] Recurrent myocarditis with normal LVEF can be presented with an increase in troponin and creatine kinase (CK) MB and multiple foci of DE in CMR.[30]
There are limited recommendations about the treatment of MCpEF depending on the first presentation, such as use of beta-blockers or concomitant beta-blocker and angiotensin-converting enzyme inhibitors in addition to some kind of supplements (such as coenzyme Q10) with concomitant advice to rest and abstinence of participation in competitive sports.[4],[5],[30],[31] In some cases, patients have been discharged with no medications.[32]
Patients can be discharged after normalization of myocardial enzymes, but even after discharge, they must be followed for a longer period of time with periodic monitoring of ventricular function.[4] In a retrospective study, 9% of patients with myocarditis and LVEF more than 50 percent had a drop in LV function at discharge and a subgroup of them needed inotropic or even extracorporeal membrane oxygenation support. This group had a higher level of brain natriuretic peptide, troponin I, and CK levels on presentation.[33]
EMB has been the gold standard for the diagnosis of myocarditis. Although its valuable results can lead to specific therapeutic recommendations (in contrast to diagnostic limitations with CMR study[34],[35],[36]), a number of studies recommend that EMB in the presence of preserved systolic function should be reserved for clinical or echocardiographic deterioration such as severe heart failure, life-threatening arrhythmias or in the presence of clinically suspicion of cardiac sarcoidosis, giant cell myocarditis, or eosinophilic myocarditis.[1],[4],[8] The most common reported virus in EMB of this population has been enterovirus,[30] and differentiating the exact cause of the disease may lead to the change in treatment strategies.
Role of implantable cardioverter defibrillator implantation
Myocarditis in different types is known as an important cause of sudden cardiac death in young athletes under 35 years (5%–11% of sickle cell disease episodes under 40). It is also a leading cause of death in children and young adults.[5] Malignant arrhythmias as a potential cause of sudden cardiac death have been reported in biopsy-proven MCpEF which has been led to implantable cardioverter defibrillator (ICD) implantation or anti-arrhythmic use in acute phase to more than 12 months after initial presentation.[37] Sudden cardiac death which can be related to focal inflammation and necrosis (MCpEF) has also been reported in postmortem autopsies.[5]
Due to transient source of arrhythmia in myocarditis, ICD implantation is not usually recommended except in the presence of life-threatening events.[31] In ITAMY study in Italy, only 6 patients in myocarditis group out of 374 had ICD implantation, and the main causes were syncope or sustained ventricular tachycardia.[8] In a relatively small study on 54 patients with LVEF more than 40%, inflammatory process in CMR has been correlated with several episodes of nonsustained ventricular tachycardia, the more frequent episodes, the more affected segments.[38]
The use of wearable cardioverter defibrillator has been studied in heart failure patients with reduced EF as a bridge to avoid permanent ICD implantation in a subgroup of patients who are at risk of life-threatening arrhythmia but does not fulfill ICD implantation criteria (based on international guidelines).[39] This device has been also evaluated in early inflammatory phase of acute myocarditis in order to prevent sudden cardiac death with acceptable results.[31]
Rarely, complete heart block may even occur in the setting of acute myocarditis with preserved EF which may impact on hospitalization course and follow-up.[29]
ConclusionMyocarditis with preserved EF is usually considered in the presence of clinical symptoms (especially ACS-like presentation) and evidence of myocarditis in electrocardiogram or imaging modalities with LVEF more than 45%–50%. Patient prognosis is considered to be better than other types with heart failure presentation or ventricular arrhythmia.[29] Treatment strategy is based on the clinical presentation and long-term follow-up is recommended. Complementary details about the disease remained to be determined in future clinical trials in terms of preferred diagnostic modality, best medical approach, and identifying the role of wearable ICD in this setting.
Ethical clearance
This review article does not contain any specific patient's data and all the resources are mentioned in reference part.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
References
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