Tools
EBV-Associated Myopericarditis
Introduction
Epstein-Barr virus (EBV) is a widely distributed virus from the herpesvirus family (human herpesvirus 4), containing a double-stranded DNA core enclosed by proteins.[1] EBV spreads through close contact between susceptible individuals and asymptomatic carriers of EBV. The primary source of virus transmission is through bodily fluids, primarily saliva.[2] Instances of spread are documented in the context of stem cell and organ transplantation and blood transfusion.[3] EBV can cause aggressive and catastrophic diseases in immunocompromised individuals, like chronic EBV disease, hemophagocytic lymphohistiocytosis, autoimmune phenomena, and some tumors (Hodgkin lymphoma, non-Hodgkin lymphoma, nasopharyngeal cancer, and Burkitt lymphoma).[4][5]
Cardiovascular manifestations and sequelae from EBV infection are less common yet significant, resulting from direct toxicity (lysing of host cells or cleavage of host proteins by viral proteases) and immune-mediated cellular injury. These complications have been noted in individuals whose immune systems are compromised. Complications include dilatation of the coronary artery, aneurysm of the coronary artery, progression of coronary artery disease, myopericarditis, valvular disease, and pulmonary hypertension, among others.[6] If not managed promptly and appropriately, fatal outcomes can occur.[7]
Etiology
Register For Free And Read The Full Article
Search engine and full access to all medical articles- 10 free questions in your specialty
- Free CME/CE Activities
- Free daily question in your email
- Save favorite articles to your dashboard
- Emails offering discounts
Learn more about a Subscription to StatPearls Point-of-Care
Etiology
EBV has an outer layer of glycoproteins. These are essential for binding to and infiltrating specific host cells, primarily B-cells and epithelial cells.[8] EBV mutates B-cells to duplicate genetic material. This process converts B-cells into memory B-cells, which can circulate in the bloodstream or remain inactive until an external trigger prompts the revival.[9]
B lymphocytes, T lymphocytes, epithelial cells, and myocytes are host cells for EBV. Unlike herpes simplex (HSV) or cytomegalovirus (CMV), EBV transforms B-cells without causing noticeable cell damage.[10] Given the latency of EBV, host factors such as immunosuppression may lead to virus reactivation, leading to clinical manifestations such as infectious mononucleosis and autoimmune phenomena.[8][11][12][13] Immunosuppression is associated with aggressive lymphoproliferative disorders in organ transplant recipients and other immunocompromised patients, first described in observations of EBV within tissue samples of lymphoma patients.[8][14]
Epidemiology
Approximately 90% to 95% of the global adult population has experienced EBV infection.[15] In the United States, one seroprevalence study estimated the prevalence of EBV among children and adolescents aged 6 to 19 to be 66.5%.[16] Specifically, children aged 6 to 8 exhibited an approximate 54% prevalence, while adolescents aged 18 to 19 displayed a prevalence of 82.9%. The Mexican-American children and adolescents in the study exhibited a higher EBV prevalence in comparison to their non-Hispanic black and white counterparts. In low and middle-income countries, the estimated population seroprevalence of EBV ranged from 92.1% to 94.8%, with the highest seropositivity in those aged >40 years.[17] In the United Kingdom, a seroprevalence study estimated an overall population prevalence of 85.3%, with females reaching seropositivity younger than males.[18]
Other findings included higher seroprevalence in those with a white ethnicity, lower body mass index, and a non-smoking history. Factors such as larger household sizes, lower household incomes, decreased parental education, early life maternal deprivation, and foreign birth are all associated with a heightened prevalence of EBV infection among children and adolescents.[19][16]
Myopericarditis is infrequent in children and adolescents, with a projected occurrence rate of 1 to 2 cases per 100,000 individuals.[20] In cases of EBV associated with coronary disease, evidence is limited to observational studies or case reports, with one study of 299 patients with percutaneous coronary intervention indicating higher measures of pro-inflammatory cytokines and EBV-related proteins among all patients with acute myocardial infarctions.[21] In an anatomical study of 142 patients with cardiac dilation and histological evidence of myocarditis, 9 patients were found positive for EBV DNA.[22]
Pathophysiology
The progression of viral myocarditis-induced damage unfolds in 2 distinct phases. The initial phase spans roughly 1 week and is characterized by viral infiltration into the myocardium, viral replication, and subsequent cell lysis. Neutralizing antibodies are generated, leading to the elimination or attenuation of the virus by macrophages and natural killer cells during the innate immune response.[23][24]
Following this stage, the myocardium experiences an influx of inflammatory cells, accompanied by immune system activation that includes the production of antibodies targeting cardiac myocytes through an adaptive immune response driven by T cells. This phase endures for several weeks or months and is associated with varying extents of myocardial impairment, ranging from minimal to severe. Recovery may occur with the elimination of pathogens, but in susceptible individuals such as those with immune dysfunction, chronic inflammation, remodeling, dilated cardiomyopathy, and cardiac failure may occur.[24] In the murine model, characteristic pathological findings encompass multiple localized regions of myocyte loss, sheets of fibrosis, and diffusely scattered calcified deposits throughout all layers and chambers of the cardiac muscle.[23]
Histopathology
Pathologically, inflammatory cell infiltrates associated with or without myocyte necrosis are required to identify myocarditis when viewing stained heart tissue sections.[25] Autoantibodies to cardiac antigens, such as cardiac myosin, may be performed. Based on the associated clinical history and prodrome, findings may be consistent with either fulminant lymphocytic myocarditis or acute lymphocytic myocarditis.[26] Therefore, findings may suggest a viral etiology on histopathology. A concordant clinical history is required to confirm viral myocarditis.
History and Physical
The clinical presentation encompasses asymptomatic conditions to abrupt fatality attributable to either fulminant heart failure or malignant ventricular arrhythmias. The clinical presentation holds notable prognostic significance, and individuals with heart failure symptoms at the outset are markedly prone to requiring transplantation and facing cardiac mortality.[27]
Symptoms mostly resemble a cold, including fever, fatigue, cough, and odynophagia. Other symptoms encompass precordial chest pain, palpitations, polymyalgia, and asthenia.[28] Additionally, there is mild, non-radiating chest discomfort, breathlessness, dizziness, and decreased ability to exercise, all absent during rest.[29] The emergence of myocarditis in children and adults might be preceded by a viral prodrome characterized by symptoms like rash, myo-arthralgias, and gastrointestinal and respiratory issues, occurring anywhere from several days to a few weeks prior.[30][24][31]
In cases where pericardial involvement is predominant, individuals may describe the pain as sharp, exacerbated by coughing or deep breaths, and alleviated by assuming a forward-leaning position. When there is substantial myocardial engagement, the pain might be continuous, posing challenges while distinguishing it from myocardial ischemic pain, particularly among those with cardiovascular risk factors.[32] Additionally, they might exhibit prevalent symptoms of heart failure like breathlessness, orthopnea, swelling in the lower extremities, and fatigue. Infrequent symptoms encompass arrhythmias, syncope, and sudden cardiac arrest.[33]
Physical examination findings can vary but commonly include fever, a pericardial friction rub, and indications of heart failure. [34] Furthermore, enlarged cervical lymph nodes and tonsillar hypertrophy with exudates are present. Conversely, symptoms like hepatomegaly and splenomegaly are notably absent. Manifestations of systemic illness that might contribute to the underlying cause include autoimmune disorders, systemic lupus erythematosus, vaccinations, chemotherapy, and immune checkpoint inhibitor therapy.[35][36]
These subtle presentations can sometimes lead to complications abruptly, escalating into life-threatening scenarios. Myopericarditis exhibits diverse progression patterns, ranging from fatal outcomes attributed to severe systolic dysfunction or ventricular arrhythmias to extended development into dilated cardiomyopathy.[37] Upon discharge from inpatient care, vigilant monitoring for several weeks is imperative, especially in cases where the possibility of heart failure development persists.
Evaluation
Laboratory Studies
Atypical lymphocytosis is typically evident in peripheral smears.[8] Serological testing is generally used to ascertain whether a patient has exposure to EBV. Routine viral serology tests are not typically beneficial for the diagnostic process, as their outcomes seldom influence treatment decisions. In determining acute infection with EBV, a heterophile antibody test can detect immunoglobulin M (IgM) antibodies targeting EBV. False positive results may occur due to the cross-reactivity of IgM with other viral infections, hematological malignancies, and autoimmune disorders.[38] Despite these caveats, utilizing heterophile antibody testing as an initial approach is advantageous due to the affordability, rapidity, and sensitivity range of 63% to 84% and specificity range of 84% to 100%.[39]
Given the challenges of using serological markers to diagnose EBV infection, polymerase chain reaction (PCR) methods have been demonstrated to accurately detect primary EBV infection and reactivation in sera without heterophile antibodies.[38] Sensitivity and specificity among pediatric populations with infectious mononucleosis were 77% (95% CI 66-86%) and specificity 98% (95% CI 93-100%) respectively.[40] Furthermore, PCR may be applied to paraffin-embedded tissues with assay sensitivities as low as 50 copies of EBV DNA per reaction.[41] PCR has replaced culture as the primary means of detecting EBV in tissue.[42]
Myopericarditis can result in elevated levels of inflammatory markers, including erythrocyte sedimentation rate, C-reactive protein, white blood cells, and cardiac biomarkers.[43] A comprehensive blood analysis is recommended for all patients to rule out thyroid disorders and hepatitis and assess renal function. This approach thoroughly evaluates the patient's overall health and contributing factors.[44]
Electrocardiogram
Characteristic electrocardiogram patterns in pericarditis encompass a widespread, concave elevation of ST segments and PR depression. These alterations, generalized T-wave modifications, or inversions can vary depending on the extent of myocardial engagement. While ST-segment alterations are generally diffuse, localized ECG shifts (inferolateral or anterolateral) can also manifest contingent on the degree of involvement. Frequent arrhythmias involve supraventricular or ventricular ectopic beats and brief episodes of ventricular arrhythmias.[45][46]
Chest Radiography
Pericardial effusion may manifest as a rounded cardiac silhouette on a chest X-ray. Echocardiography typically confirms effusion, constriction, or tamponade.[47]
Echocardiogram
The echocardiographic characteristics of myocarditis are non-specific. However, as a part of the routine evaluation, an echocardiogram is ordered, which may reveal normal heart function along with a minimal or absent pericardial effusion. The echocardiographic presentation can resemble various patterns, including dilated, hypertrophic, restrictive, or right ventricular cardiomyopathy, along with manifestations similar to coronary artery disease. Additionally, the echocardiogram assesses the functioning of both the left and right ventricles and identifies any abnormalities related to valvular heart disease.[48]
Coronary Angiography
When there is suspicion of acute coronary syndrome, and the clinical presentation is reminiscent of coronary artery disease, this diagnostic approach is considered the definitive method to exclude its presence. In cases where traditional contraindications are not applicable, CT coronary angiography (CTCA) might be an alternative. For young patients exhibiting typical myopericarditis symptoms, coronary angiography is typically unnecessary. However, for individuals with risk factors associated with atherosclerotic cardiovascular disease, distinguishing between myopericarditis and myocardial ischemia through non-invasive testing is challenging. In such instances, cardiac catheterization is required to rule out acute coronary syndrome.[49][44]
Cardiac Magnetic Resonance Imaging
Cardiac MRI is a promising technique for assessing individuals suspected of having myocarditis. The revised Lake Louis criteria now encompass T1 and T2 criteria for diagnosing myocarditis. T1 imaging reveals an elevated T1 relaxation time, while T2 imaging demonstrates an increased T2 relaxation time or Signal Intensity (SI). In addition, gadolinium-enhanced CMR sequences unveil irregular hyperenhancement patterns within the myocardial tissue.[50] Such changes are associated with a higher rate of mortality, including sudden cardiac death.[51]
Endomyocardial Biopsy
Endomyocardial biopsy (EMB) is warranted in select cases of severely ill patients who demonstrate clinical deterioration after standard supportive treatment. EMB is the gold standard for diagnosis. According to the consensus scientific statement of the European Society of Cardiology, the American Heart Association, and the American College of Cardiology, a class I indication for performing EMB in myocarditis is in cases of new-onset heart failure lasting less than 2 weeks, involving preserved ventricle dimensions but compromised hemodynamics.[52] Additionally, EMB is indicated as a class I procedure for patients experiencing new-onset heart failure lasting 2 weeks to 3 months, characterized by dilated ventricles, tachyarrhythmia or bradyarrhythmia, and a lack of response to therapy within 1 to 2 weeks.[53]
Treatment / Management
For the majority of patients, the overall prognosis of this condition is favorable, and long-term complications are rare. The available data to inform the management of myopericarditis are currently limited.[54] Viral myopericarditis is mainly supportive and follows the general management of myopericarditis.
Hemodynamically Unstable Patients
Patients presenting with a life-threatening condition should be directed to specialized facilities equipped with the capacity for hemodynamic monitoring, cardiac catheterization, expertise in EMB, and cardiac surgery. In instances of hemodynamic instability, the implementation of a mechanical cardio-pulmonary assist device is necessary to bridge either recovery or heart transplantation.[55] The consideration for cardiac transplantation should be postponed during the acute phase, as there is a potential for spontaneous recovery. However, this option is considered for hemodynamically unstable myocarditis patients, including those with giant cell myocarditis, if optimal pharmacological support and mechanical assistance fail to stabilize the patient.[56]
Hemodynamically Stable Patients
For patients experiencing stable heart failure, the recommended treatment includes diuretics, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and beta-adrenergic blockers. If individuals continue to show symptoms of heart failure despite receiving optimal care, one should consider adding aldosterone antagonists.[57]
When the initial manifestation resembles pericarditis symptoms, and the left ventricular function remains intact, the first-line treatment involves Nonsteroidal anti-inflammatory drugs (NSAIDs). However, in cases where substantial myocardial involvement is evident, NSAIDs are approached cautiously due to their potential to exacerbate myocardial function and cardiac failure.[58] In such instances, NSAIDs are administered at minimal dosages to avoid compromising myocardial health.[44]
Arrhythmia
Ventricular or atrial arrhythmias and heart block are potential complications of acute myocarditis. In hemodynamically stable tachyarrhythmia without signs of peripheral hypoperfusion, β-blocker therapy is advised. Patients with sustained ventricular arrhythmias are recommended amiodarone and dofetilide as suitable treatment options. When necessary, heart block is addressed by implementing a temporary pacemaker followed by a permanent pacemaker. As the acute phase subsides, standard recommendations include an implantable cardioverter defibrillator during the chronic stage.[49]
Avoidance of Exercise
During acute myocarditis, physical activity should be restricted. Patients are discouraged from engaging in competitive sports for at least 3 to 6 months following the acute episode. Subsequent guidance hinges on regular follow-up involving clinical evaluation, echocardiography, and Holter monitoring.[59][60](B3)
Immunomodulatory Therapy
There is no approved antiviral therapy, but vaccination is a future possibility.[61](B3)
In cases of myocarditis that do not respond to standard heart failure treatments, including both viral and autoimmune types, especially those driven by autoantibodies, intravenous immunoglobulin (IVIG) may be employed to minimize adverse effects.[62]
Immunosuppressive Therapy
The safety and effectiveness of immunosuppressive regimens for myocarditis are studied using steroids alone, combined with azathioprine or cyclosporine A, azathioprine, and steroids. Limited information is available regarding the use of other medications. Reports on treatment outcomes primarily focus on chronic cases that are negative for viral involvement.[56]
Differential Diagnosis
Acute Coronary Syndrome
Cardiovascular magnetic resonance imaging is vital in distinguishing between different causes of acute coronary syndromes. This significance is pronounced due to the vague and overlapping signs and symptoms, which resemble those of other conditions like myopericarditis.[63] The viral prodrome of EBV-associated myocarditis rules out acute coronary syndrome.
Chagas Heart Disease (CHD)
As a result of the protozoan parasite Trypanosoma cruzi, CHD is the primary cause of known infectious myocarditis globally, albeit concentrated within the Americas.[64] CHD comprises 2 distinct clinical phases: the acute phase, which emerges shortly following infection and persists for 4 to 8 weeks, and the chronic phase, which evolves over 10 to 30 years. The PCR is the most sensitive diagnostic tool in the acute phase of Chagas disease.[65] In around one-third of cases, the chronic phase develops from asymptomatic to symptomatic.
Cardiac Tamponade
Pericarditis frequently involves pericardial effusion, which could progress to cardiac tamponade.[66] Cardiac tamponade is a condition that arises when there is a sudden and excessive buildup of fluid within the pericardial cavity.
Prognosis
Differentiating acute myopericarditis from pericarditis is essential. Common viruses, including parvovirus B19, adenovirus, herpes viruses, hepatitis viruses, human immunodeficiency virus, and enteroviruses, can induce heart inflammation, leading to acute pericarditis and myocarditis.[67] EBV rarely contributes to these conditions in individuals with intact immune systems.[13] The prognosis can be jeopardized by heart failure, particularly in cases of severe onset. Due to the diverse clinical manifestations of EBV, the severity of such manifestations, and the interplay with host immune factors, the prognosis of EBV-related myopericarditis can vary. In general, patients experiencing acute decompensated heart failure, persistent arrhythmias, and a left ventricular ejection fraction below 50%, or those necessitating inotropic agents, vasopressors, or mechanical cardiac assistance, are more likely to encounter unfavorable cardiovascular outcomes.[68][69]
Complications
Complications may vary according to the interplay between EBV and the host immune system, but known sequelae of viral (including EBV) related cardiac manifestations include:
Deterrence and Patient Education
Patients with EBV infection should be informed about potential complications, which range from asymptomatic conditions to life-threatening outcomes such as coronary artery dilation, valvular heart disease, and heart failure.[6] However, these fatal complications can be prevented with prompt and appropriate management. Transmission of EBV occurs primarily through close contact with infected individuals, mainly saliva.[2] Regular precautions that include awareness and personal hygiene prevent viral transmission.
Patients who develop myopericarditis and are hemodynamically unstable must have a timely referral to a highly specialized cardiac center. Other patients should receive symptomatic management following the principles of heart failure treatment. Patients with heart failure are more susceptible to unfavorable cardiac complications, so close monitoring and proper medical care are crucial. Timely and thorough cardiac evaluation is paramount to detecting potential complications and providing appropriate interventions.
In summary, educating patients about the potential complications of EBV infection, emphasizing the importance of transmission prevention, ensuring timely referrals for severe cases, and implementing appropriate management strategies can contribute to better outcomes and a reduced risk of complications.
Enhancing Healthcare Team Outcomes
Patients with EBV-associated myocarditis face a significant risk of mortality when not promptly and effectively treated. Therefore, early management is crucial for reducing morbidity and mortality. The care of individuals with EBV-associated myocarditis demands a collaborative approach involving healthcare professionals to provide patient-centered care and enhance overall outcomes.
A multidisciplinary team, including cardiologists, emergency medicine clinicians, critical care clinicians, advanced practitioners, nurses, pharmacists, physiotherapists, and other healthcare providers, should possess the clinical skills and knowledge to diagnose and manage EBV-associated myocarditis. The condition involves expertise in recognizing diverse clinical presentations and proficiency in diagnostic techniques such as echocardiography, cardiac MRI, and endomyocardial biopsy.[75][76] Furthermore, educating patients and caregivers about the condition's origins, symptoms, and utilization of diagnostic tools is vital in preventing cardiac complications and reducing morbidity.
A strategic approach involving evidence-based strategies to optimize treatment plans while minimizing adverse effects is crucial. Ethical considerations should steer decision-making, ensuring that informed consent is secured and patient autonomy is honored in the decision-making process. Every healthcare professional should be conscious of their responsibilities and contribute unique expertise to the patient's care plan, fostering a multidisciplinary approach.
Effective interprofessional communication is paramount, allowing for seamless information exchange and collaborative decision-making among team members. Care coordination is vital in ensuring that the patient's path from diagnosis to treatment and follow-up is effectively managed, minimizing errors and improving patient safety. By embracing these principles of skill, strategy, ethics, responsibilities, interprofessional communication, and care coordination, healthcare professionals can deliver integrated patient-centered care.
References
Zhang N, Zuo Y, Jiang L, Peng Y, Huang X, Zuo L. Epstein-Barr Virus and Neurological Diseases. Frontiers in molecular biosciences. 2021:8():816098. doi: 10.3389/fmolb.2021.816098. Epub 2022 Jan 10 [PubMed PMID: 35083281]
Castillo A, Giraldo S, Guzmán N, Bravo LE. Factors associated with the presence of the Epstein-Barr virus in the oral cavity of high school students from the city of Cali (Colombia). Enfermedades infecciosas y microbiologia clinica (English ed.). 2022 Mar:40(3):113-120. doi: 10.1016/j.eimce.2021.12.005. Epub 2022 Jan 6 [PubMed PMID: 35000871]
Dunmire SK, Verghese PS, Balfour HH Jr. Primary Epstein-Barr virus infection. Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology. 2018 May:102():84-92. doi: 10.1016/j.jcv.2018.03.001. Epub 2018 Mar 5 [PubMed PMID: 29525635]
Nowalk A, Green M. Epstein-Barr Virus. Microbiology spectrum. 2016 Jun:4(3):. doi: 10.1128/microbiolspec.DMIH2-0011-2015. Epub [PubMed PMID: 27337443]
Houen G, Trier NH. Epstein-Barr Virus and Systemic Autoimmune Diseases. Frontiers in immunology. 2020:11():587380. doi: 10.3389/fimmu.2020.587380. Epub 2021 Jan 7 [PubMed PMID: 33488588]
Muneuchi J, Ohga S, Ishimura M, Ikeda K, Yamaguchi K, Nomura A, Takada H, Abe Y, Hara T. Cardiovascular complications associated with chronic active Epstein-Barr virus infection. Pediatric cardiology. 2009 Apr:30(3):274-81. doi: 10.1007/s00246-008-9343-8. Epub 2009 Jan 30 [PubMed PMID: 19184184]
Chen X, Li Y, Deng L, Wang L, Zhong W, Hong J, Chen L, Yang J, Huang B, Xiao X. Cardiovascular involvement in Epstein-Barr virus infection. Frontiers in immunology. 2023:14():1188330. doi: 10.3389/fimmu.2023.1188330. Epub 2023 May 22 [PubMed PMID: 37292213]
Odumade OA, Hogquist KA, Balfour HH Jr. Progress and problems in understanding and managing primary Epstein-Barr virus infections. Clinical microbiology reviews. 2011 Jan:24(1):193-209. doi: 10.1128/CMR.00044-10. Epub [PubMed PMID: 21233512]
Level 3 (low-level) evidenceSarwari NM, Khoury JD, Hernandez CM. Chronic Epstein Barr virus infection leading to classical Hodgkin lymphoma. BMC hematology. 2016:16():19. doi: 10.1186/s12878-016-0059-3. Epub 2016 Jul 19 [PubMed PMID: 27437106]
Michelow P, Wright C, Pantanowitz L. A review of the cytomorphology of Epstein-Barr virus-associated malignancies. Acta cytologica. 2012:56(1):1-14. doi: 10.1159/000334235. Epub 2012 Jan 4 [PubMed PMID: 22236740]
Henle G, Henle W, Diehl V. Relation of Burkitt's tumor-associated herpes-ytpe virus to infectious mononucleosis. Proceedings of the National Academy of Sciences of the United States of America. 1968 Jan:59(1):94-101 [PubMed PMID: 5242134]
Nguyen ADK, Siu R, Kleinschmidt G, Sood BP, Shandiz EE. Epstein-Barr virus reactivation-related meningoencephalitis with transverse myelitis in pregnancy. Clinical case reports. 2023 Sep:11(9):e7923. doi: 10.1002/ccr3.7923. Epub 2023 Sep 21 [PubMed PMID: 37744622]
Level 3 (low-level) evidenceSausen DG, Bhutta MS, Gallo ES, Dahari H, Borenstein R. Stress-Induced Epstein-Barr Virus Reactivation. Biomolecules. 2021 Sep 18:11(9):. doi: 10.3390/biom11091380. Epub 2021 Sep 18 [PubMed PMID: 34572593]
Henle W. Evidence for viruses in acute leukemia and Burkitt's tumor. Cancer. 1968 Apr:21(4):580-6 [PubMed PMID: 4868472]
Cohen JI. Epstein-Barr virus infection. The New England journal of medicine. 2000 Aug 17:343(7):481-92 [PubMed PMID: 10944566]
Dowd JB, Palermo T, Brite J, McDade TW, Aiello A. Seroprevalence of Epstein-Barr virus infection in U.S. children ages 6-19, 2003-2010. PloS one. 2013:8(5):e64921. doi: 10.1371/journal.pone.0064921. Epub 2013 May 22 [PubMed PMID: 23717674]
Level 2 (mid-level) evidenceSharifipour S, Davoodi Rad K. Seroprevalence of Epstein-Barr virus among children and adults in Tehran, Iran. New microbes and new infections. 2020 Mar:34():100641. doi: 10.1016/j.nmni.2019.100641. Epub 2020 Jan 7 [PubMed PMID: 32025310]
Kuri A, Jacobs BM, Vickaryous N, Pakpoor J, Middeldorp J, Giovannoni G, Dobson R. Epidemiology of Epstein-Barr virus infection and infectious mononucleosis in the United Kingdom. BMC public health. 2020 Jun 12:20(1):912. doi: 10.1186/s12889-020-09049-x. Epub 2020 Jun 12 [PubMed PMID: 32532296]
Gares V, Panico L, Castagne R, Delpierre C, Kelly-Irving M. The role of the early social environment on Epstein Barr virus infection: a prospective observational design using the Millennium Cohort Study. Epidemiology and infection. 2017 Dec:145(16):3405-3412. doi: 10.1017/S0950268817002515. Epub 2017 Dec 5 [PubMed PMID: 29202893]
Ace O, Domb S. Myocarditis as the initial presentation of Epstein-Barr virus infection in a 17-year-old male patient. Canadian family physician Medecin de famille canadien. 2019 Dec:65(12):897-899 [PubMed PMID: 31831489]
Binkley PF, Cooke GE, Lesinski A, Taylor M, Chen M, Laskowski B, Waldman WJ, Ariza ME, Williams MV Jr, Knight DA, Glaser R. Evidence for the role of Epstein Barr Virus infections in the pathogenesis of acute coronary events. PloS one. 2013:8(1):e54008. doi: 10.1371/journal.pone.0054008. Epub 2013 Jan 17 [PubMed PMID: 23349778]
Chimenti C, Russo A, Pieroni M, Calabrese F, Verardo R, Thiene G, Russo MA, Maseri A, Frustaci A. Intramyocyte detection of Epstein-Barr virus genome by laser capture microdissection in patients with inflammatory cardiomyopathy. Circulation. 2004 Dec 7:110(23):3534-9 [PubMed PMID: 15557377]
Sole MJ, Liu P. Viral myocarditis: a paradigm for understanding the pathogenesis and treatment of dilated cardiomyopathy. Journal of the American College of Cardiology. 1993 Oct:22(4 Suppl A):99A-105A [PubMed PMID: 8376702]
Level 3 (low-level) evidenceSozzi FB, Gherbesi E, Faggiano A, Gnan E, Maruccio A, Schiavone M, Iacuzio L, Carugo S. Viral Myocarditis: Classification, Diagnosis, and Clinical Implications. Frontiers in cardiovascular medicine. 2022:9():908663. doi: 10.3389/fcvm.2022.908663. Epub 2022 Jun 20 [PubMed PMID: 35795363]
Aretz HT, Billingham ME, Edwards WD, Factor SM, Fallon JT, Fenoglio JJ Jr, Olsen EG, Schoen FJ. Myocarditis. A histopathologic definition and classification. The American journal of cardiovascular pathology. 1987 Jan:1(1):3-14 [PubMed PMID: 3455232]
Cooper LT Jr. Myocarditis. The New England journal of medicine. 2009 Apr 9:360(15):1526-38. doi: 10.1056/NEJMra0800028. Epub [PubMed PMID: 19357408]
ElAmm CA, Al-Kindi SG, Oliveira GH. Characteristics and Outcomes of Patients With Myocarditis Listed for Heart Transplantation. Circulation. Heart failure. 2016 Dec:9(12):. pii: e003259. Epub [PubMed PMID: 27927755]
Sharif N, Dehghani P. Emergency files: acute pericarditis, myocarditis, and worse! Canadian family physician Medecin de famille canadien. 2013 Jan:59(1):39-41 [PubMed PMID: 23341656]
Olejniczak M, Schwartz M, Webber E, Shaffer A, Perry TE. Viral Myocarditis-Incidence, Diagnosis and Management. Journal of cardiothoracic and vascular anesthesia. 2020 Jun:34(6):1591-1601. doi: 10.1053/j.jvca.2019.12.052. Epub 2020 Jan 7 [PubMed PMID: 32127272]
Roubille F, Gahide G, Moore-Morris T, Granier M, Davy JM, Vernhet H, Piot C. Epstein Barr virus (EBV) and acute myopericarditis in an immunocompetent patient: first demonstrated case and discussion. Internal medicine (Tokyo, Japan). 2008:47(7):627-9 [PubMed PMID: 18379149]
Level 3 (low-level) evidenceFung RCM, Hon KL, Leung AKC. Acute Myocarditis in Children: An Overview of Treatment and Recent Patents. Recent patents on inflammation & allergy drug discovery. 2020:14(2):106-116. doi: 10.2174/1872213X14666200204103714. Epub [PubMed PMID: 32013855]
Level 3 (low-level) evidenceDec GW Jr, Waldman H, Southern J, Fallon JT, Hutter AM Jr, Palacios I. Viral myocarditis mimicking acute myocardial infarction. Journal of the American College of Cardiology. 1992 Jul:20(1):85-9 [PubMed PMID: 1607543]
Harris KM, Mackey-Bojack S, Bennett M, Nwaudo D, Duncanson E, Maron BJ. Sudden Unexpected Death Due to Myocarditis in Young People, Including Athletes. The American journal of cardiology. 2021 Mar 15:143():131-134. doi: 10.1016/j.amjcard.2020.12.028. Epub 2020 Dec 19 [PubMed PMID: 33347841]
Schultz JC, Hilliard AA, Cooper LT Jr, Rihal CS. Diagnosis and treatment of viral myocarditis. Mayo Clinic proceedings. 2009 Nov:84(11):1001-9. doi: 10.1016/S0025-6196(11)60670-8. Epub [PubMed PMID: 19880690]
Ammirati E, Moslehi JJ. Diagnosis and Treatment of Acute Myocarditis: A Review. JAMA. 2023 Apr 4:329(13):1098-1113. doi: 10.1001/jama.2023.3371. Epub [PubMed PMID: 37014337]
Kyaw T, Drummond G, Bobik A, Peter K. Myocarditis: causes, mechanisms, and evolving therapies. Expert opinion on therapeutic targets. 2023 Mar:27(3):225-238. doi: 10.1080/14728222.2023.2193330. Epub 2023 Mar 22 [PubMed PMID: 36946552]
Level 3 (low-level) evidenceAdegbala O, Olagoke O, Akintoye E, Adejumo AC, Oluwole A, Jara C, Williams K, Briasoulis A, Afonso L. Predictors, Burden, and the Impact of Arrhythmia on Patients Admitted for Acute Myocarditis. The American journal of cardiology. 2019 Jan 1:123(1):139-144. doi: 10.1016/j.amjcard.2018.09.017. Epub 2018 Sep 27 [PubMed PMID: 30539745]
Marshall-Andon T, Heinz P. How to use … the Monospot and other heterophile antibody tests. Archives of disease in childhood. Education and practice edition. 2017 Aug:102(4):188-193. doi: 10.1136/archdischild-2016-311526. Epub 2017 Jan 27 [PubMed PMID: 28130396]
Womack J, Jimenez M. Common questions about infectious mononucleosis. American family physician. 2015 Mar 15:91(6):372-6 [PubMed PMID: 25822555]
Jiang SY, Yang JW, Shao JB, Liao XL, Lu ZH, Jiang H. Real-time polymerase chain reaction for diagnosing infectious mononucleosis in pediatric patients: A systematic review and meta-analysis. Journal of medical virology. 2016 May:88(5):871-6. doi: 10.1002/jmv.24402. Epub 2016 Jan 5 [PubMed PMID: 26455510]
Level 1 (high-level) evidenceRyan JL, Fan H, Glaser SL, Schichman SA, Raab-Traub N, Gulley ML. Epstein-Barr virus quantitation by real-time PCR targeting multiple gene segments: a novel approach to screen for the virus in paraffin-embedded tissue and plasma. The Journal of molecular diagnostics : JMD. 2004 Nov:6(4):378-85 [PubMed PMID: 15507678]
Haque T, Crawford DH. PCR amplification is more sensitive than tissue culture methods for Epstein-Barr virus detection in clinical material. The Journal of general virology. 1997 Dec:78 ( Pt 12)():3357-60 [PubMed PMID: 9400988]
Lampejo T, Durkin SM, Bhatt N, Guttmann O. Acute myocarditis: aetiology, diagnosis and management. Clinical medicine (London, England). 2021 Sep:21(5):e505-e510. doi: 10.7861/clinmed.2021-0121. Epub [PubMed PMID: 34507935]
Manda YR, Baradhi KM. Myopericarditis. StatPearls. 2023 Jan:(): [PubMed PMID: 30521197]
Marinella MA. Electrocardiographic manifestations and differential diagnosis of acute pericarditis. American family physician. 1998 Feb 15:57(4):699-704 [PubMed PMID: 9490993]
Level 3 (low-level) evidenceWatanabe M, Panetta GL, Piccirillo F, Spoto S, Myers J, Serino FM, Costantino S, Di Sciascio G. Acute Epstein-Barr related myocarditis: An unusual but life-threatening disease in an immunocompetent patient. Journal of cardiology cases. 2020 Apr:21(4):137-140. doi: 10.1016/j.jccase.2019.12.001. Epub 2019 Dec 26 [PubMed PMID: 32256861]
Level 3 (low-level) evidenceRahman A, Liu D. Pericarditis - clinical features and management. Australian family physician. 2011 Oct:40(10):791-6 [PubMed PMID: 22003482]
Level 3 (low-level) evidencePinamonti B, Alberti E, Cigalotto A, Dreas L, Salvi A, Silvestri F, Camerini F. Echocardiographic findings in myocarditis. The American journal of cardiology. 1988 Aug 1:62(4):285-91 [PubMed PMID: 3400607]
Al-Akchar M, Shams P, Kiel J. Acute Myocarditis. StatPearls. 2023 Jan:(): [PubMed PMID: 28722877]
Ferreira VM, Schulz-Menger J, Holmvang G, Kramer CM, Carbone I, Sechtem U, Kindermann I, Gutberlet M, Cooper LT, Liu P, Friedrich MG. Cardiovascular Magnetic Resonance in Nonischemic Myocardial Inflammation: Expert Recommendations. Journal of the American College of Cardiology. 2018 Dec 18:72(24):3158-3176. doi: 10.1016/j.jacc.2018.09.072. Epub [PubMed PMID: 30545455]
Greulich S, Seitz A, Müller KAL, Grün S, Ong P, Ebadi N, Kreisselmeier KP, Seizer P, Bekeredjian R, Zwadlo C, Gräni C, Klingel K, Gawaz M, Sechtem U, Mahrholdt H. Predictors of Mortality in Patients With Biopsy-Proven Viral Myocarditis: 10-Year Outcome Data. Journal of the American Heart Association. 2020 Aug 18:9(16):e015351. doi: 10.1161/JAHA.119.015351. Epub 2020 Aug 13 [PubMed PMID: 32787653]
Cooper LT, Baughman KL, Feldman AM, Frustaci A, Jessup M, Kuhl U, Levine GN, Narula J, Starling RC, Towbin J, Virmani R, American Heart Association, American College of Cardiology, European Society of Cardiology. The role of endomyocardial biopsy in the management of cardiovascular disease: a scientific statement from the American Heart Association, the American College of Cardiology, and the European Society of Cardiology. Circulation. 2007 Nov 6:116(19):2216-33 [PubMed PMID: 17959655]
Cooper LT, Baughman KL, Feldman AM, Frustaci A, Jessup M, Kuhl U, Levine GN, Narula J, Starling RC, Towbin J, Virmani R, American Heart Association, American College of Cardiology, European Society of Cardiology, Heart Failure Society of America, Heart Failure Association of the European Society of Cardiology. The role of endomyocardial biopsy in the management of cardiovascular disease: a scientific statement from the American Heart Association, the American College of Cardiology, and the European Society of Cardiology. Endorsed by the Heart Failure Society of America and the Heart Failure Association of the European Society of Cardiology. Journal of the American College of Cardiology. 2007 Nov 6:50(19):1914-31 [PubMed PMID: 17980265]
Imazio M, Brucato A, Spodick DH, Adler Y. Prognosis of myopericarditis as determined from previously published reports. Journal of cardiovascular medicine (Hagerstown, Md.). 2014 Dec:15(12):835-9. doi: 10.2459/JCM.0000000000000082. Epub [PubMed PMID: 24850499]
Tschöpe C, Cooper LT, Torre-Amione G, Van Linthout S. Management of Myocarditis-Related Cardiomyopathy in Adults. Circulation research. 2019 May 24:124(11):1568-1583. doi: 10.1161/CIRCRESAHA.118.313578. Epub [PubMed PMID: 31120823]
Caforio AL, Pankuweit S, Arbustini E, Basso C, Gimeno-Blanes J, Felix SB, Fu M, Heliö T, Heymans S, Jahns R, Klingel K, Linhart A, Maisch B, McKenna W, Mogensen J, Pinto YM, Ristic A, Schultheiss HP, Seggewiss H, Tavazzi L, Thiene G, Yilmaz A, Charron P, Elliott PM, European Society of Cardiology Working Group on Myocardial and Pericardial Diseases. 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. European heart journal. 2013 Sep:34(33):2636-48, 2648a-2648d. doi: 10.1093/eurheartj/eht210. Epub 2013 Jul 3 [PubMed PMID: 23824828]
McMurray JJ, Adamopoulos S, Anker SD, Auricchio A, Böhm M, Dickstein K, Falk V, Filippatos G, Fonseca C, Gomez-Sanchez MA, Jaarsma T, Kober L, Lip GY, Maggioni AP, Parkhomenko A, Pieske BM, Popescu BA, Ronnevik K, Rutten FH, Schwitter J, Seferovic P, Stepinska J, Trindade PT, Voors AA, Zannad Falez, Zeiher A, Avrupa Kardiyoloji Derneği (ESC) Akut ve Kronik Kalp Yetersizliği Tani ve Tedavisi 2012 Görev Grubu, ESC Kalp Yetersizliği Birliğinin Işbirliğiyle hazirlanmiştir, Heart Failure Association. [ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012]. Turk Kardiyoloji Dernegi arsivi : Turk Kardiyoloji Derneginin yayin organidir. 2012 Oct:40 Suppl 3():77-137 [PubMed PMID: 27305718]
Lampejo T. Caution with the use of NSAIDs in myocarditis. QJM : monthly journal of the Association of Physicians. 2023 Feb 24:116(2):153. doi: 10.1093/qjmed/hcac073. Epub [PubMed PMID: 35289907]
Patriki D, Baltensperger N, Berg J, Cooper LT, Kissel CK, Kottwitz J, Lovrinovic M, Manka R, Scherff F, Schmied C, Tanner FC, Luescher TF, Heidecker B. A Prospective Pilot Study to Identify a Myocarditis Cohort who may Safely Resume Sports Activities 3 Months after Diagnosis. Journal of cardiovascular translational research. 2021 Aug:14(4):670-673. doi: 10.1007/s12265-020-09983-6. Epub 2020 May 4 [PubMed PMID: 32367345]
Level 3 (low-level) evidenceMaisch B, Alter P. Treatment options in myocarditis and inflammatory cardiomyopathy : Focus on i. v. immunoglobulins. Herz. 2018 Aug:43(5):423-430. doi: 10.1007/s00059-018-4719-x. Epub [PubMed PMID: 29947834]
Martino TA, Liu P, Sole MJ. Viral infection and the pathogenesis of dilated cardiomyopathy. Circulation research. 1994 Feb:74(2):182-8 [PubMed PMID: 8293557]
Level 3 (low-level) evidenceKindermann I, Barth C, Mahfoud F, Ukena C, Lenski M, Yilmaz A, Klingel K, Kandolf R, Sechtem U, Cooper LT, Böhm M. Update on myocarditis. Journal of the American College of Cardiology. 2012 Feb 28:59(9):779-92. doi: 10.1016/j.jacc.2011.09.074. Epub [PubMed PMID: 22361396]
Bolognesi M, Bolognesi D. Acute coronary syndrome vs. myopericarditis - not always a straightforward diagnosis. The American journal of case reports. 2013:14():221-225 [PubMed PMID: 23826474]
Level 3 (low-level) evidencePérez-Molina JA, Molina I. Chagas disease. Lancet (London, England). 2018 Jan 6:391(10115):82-94. doi: 10.1016/S0140-6736(17)31612-4. Epub 2017 Jun 30 [PubMed PMID: 28673423]
Bonney KM, Engman DM. Chagas heart disease pathogenesis: one mechanism or many? Current molecular medicine. 2008 Sep:8(6):510-8 [PubMed PMID: 18781958]
Level 3 (low-level) evidenceSharma NK, Waymack JR. Acute Cardiac Tamponade. StatPearls. 2023 Jan:(): [PubMed PMID: 30521227]
Andréoletti L, Lévêque N, Boulagnon C, Brasselet C, Fornes P. Viral causes of human myocarditis. Archives of cardiovascular diseases. 2009 Jun-Jul:102(6-7):559-68. doi: 10.1016/j.acvd.2009.04.010. Epub 2009 Jul 31 [PubMed PMID: 19664576]
Ammirati E, Cipriani M, Moro C, Raineri C, Pini D, Sormani P, Mantovani R, Varrenti M, Pedrotti P, Conca C, Mafrici A, Grosu A, Briguglia D, Guglielmetto S, Perego GB, Colombo S, Caico SI, Giannattasio C, Maestroni A, Carubelli V, Metra M, Lombardi C, Campodonico J, Agostoni P, Peretto G, Scelsi L, Turco A, Di Tano G, Campana C, Belloni A, Morandi F, Mortara A, Cirò A, Senni M, Gavazzi A, Frigerio M, Oliva F, Camici PG, Registro Lombardo delle Miocarditi. Clinical Presentation and Outcome in a Contemporary Cohort of Patients With Acute Myocarditis: Multicenter Lombardy Registry. Circulation. 2018 Sep 11:138(11):1088-1099. doi: 10.1161/CIRCULATIONAHA.118.035319. Epub [PubMed PMID: 29764898]
Piccirillo F, Watanabe M, Di Sciascio G. Diagnosis, treatment and predictors of prognosis of myocarditis. A narrative review. Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology. 2021 Sep-Oct:54():107362. doi: 10.1016/j.carpath.2021.107362. Epub 2021 Jun 27 [PubMed PMID: 34192559]
Level 3 (low-level) evidenceRached-D'Astous S, Boukas I, Fournier A, Raboisson MJ, Dahdah N. Coronary Artery Dilatation in Viral Myocarditis Mimics Coronary Artery Findings in Kawasaki Disease. Pediatric cardiology. 2016 Aug:37(6):1148-52. doi: 10.1007/s00246-016-1411-x. Epub 2016 May 27 [PubMed PMID: 27233663]
Xiao H, Hu B, Luo R, Hu H, Zhang J, Kuang W, Zhang R, Li L, Liu G. Chronic active Epstein-Barr virus infection manifesting as coronary artery aneurysm and uveitis. Virology journal. 2020 Oct 29:17(1):166. doi: 10.1186/s12985-020-01409-8. Epub 2020 Oct 29 [PubMed PMID: 33121509]
Myers JM, Fairweather D, Huber SA, Cunningham MW. Autoimmune myocarditis, valvulitis, and cardiomyopathy. Current protocols in immunology. 2013:Chapter 15():Unit 15.14.1-51. doi: 10.1002/0471142735.im1514s101. Epub [PubMed PMID: 23564686]
Fukuda Y, Momoi N, Akaihata M, Nagasawa K, Mitomo M, Aoyagi Y, Endoh K, Hosoya M. Pulmonary arterial hypertension associated with chronic active Epstein-Barr virus infection. Pediatrics international : official journal of the Japan Pediatric Society. 2015 Aug:57(4):731-4. doi: 10.1111/ped.12578. Epub 2015 Mar 25 [PubMed PMID: 25809637]
Mancio J, Bettencourt N, Oliveira M, Pires-Morais G, Ribeiro VG. Acute right ventricular myocarditis presenting with chest pain and syncope. BMJ case reports. 2013 Oct 4:2013():. doi: 10.1136/bcr-2012-007173. Epub 2013 Oct 4 [PubMed PMID: 24096068]
Level 3 (low-level) evidenceKiamanesh O, Toma M. The State of the Heart Biopsy: A Clinical Review. CJC open. 2021 Apr:3(4):524-531. doi: 10.1016/j.cjco.2020.11.017. Epub 2020 Dec 1 [PubMed PMID: 34027357]
Altman RK, Parks KA, Schlett CL, Orencole M, Park MY, Truong QA, Deeprasertkul P, Moore SA, Barrett CD, Lewis GD, Das S, Upadhyay GA, Heist EK, Picard MH, Singh JP. Multidisciplinary care of patients receiving cardiac resynchronization therapy is associated with improved clinical outcomes. European heart journal. 2012 Sep:33(17):2181-8. doi: 10.1093/eurheartj/ehs107. Epub 2012 May 21 [PubMed PMID: 22613342]
Level 2 (mid-level) evidence