Myocarditis, with a Focus on Cases Associated with COVID-19 and Vaccination

EXECUTIVE SUMMARY

• The reported incidence and mortality of myocarditis has increased over the past few decades, with between 1.5 million and 1.8 million cases of myocarditis occurring annually.
• COVID-19 and the COVID-19 messenger ribonucleic acid (mRNA) vaccines have emerged as possible triggers for myocarditis, with myocarditis due to COVID-19 infection causing a more severe disease process.
• Signs and symptoms of myocarditis may be vague and can present similarly to other disease processes, including acute coronary syndrome, heart failure, or cardiogenic shock.
• Initial evaluation for myocarditis involves obtaining serum troponins, brain natriuretic peptide, 12-lead electrocardiogram, and transthoracic echocardiogram, with cardiac magnetic resonance imaging and/or endomyocardial biopsy performed to confirm the diagnosis.
• Treatment for myocarditis is primarily supportive and involves the use of guideline-directed medical therapies for acute heart failure and/or arrhythmias if present.

Introduction

Acute myocarditis is a diagnosis that has had a significant rise in prevalence and is the center of many recent discussions in the medical literature. Much of this recent increase has been secondary to SARS-CoV-2 and the COVID-19 vaccines. Amid the global SARS-CoV-2 pandemic, acute myocarditis has become much more prevalent in patients where it was previously a rare pathology. As a result of this outbreak, it has become a disease entity necessitating new and ever evolving clinical guidelines.^1,2,3

Acute myocarditis is characterized by inflammation of the myocardium. This disease can present with a wide range of symptoms. Symptoms may be as benign as upper respiratory symptoms and malaise or may be more specific and severe, such as chest pain, arrhythmia, shock, and sudden cardiac death. The prognosis is a spectrum of full recovery to lasting heart dysfunction.^1,3,4

Similarly, the etiology of this disease is equally as diverse, including an array of infectious, toxic, and immunologic factors that trigger inflammation and cardiac injury. The exact pathophysiology is not completely understood.^1,3 Treatment for this condition revolves around preservation of heart function, addressing the underlying cause, and supportive management.⁵ This article, will focus on the epidemiology, pathophysiology, presentation, diagnosis, and treatment of acute myocarditis, especially as it relates to SARS-CoV-2 and the COVID-19 messenger ribonucleic acid (mRNA) vaccines.

Case Introduction

A 25-year-old male presents with chest pain, fatigue, and shortness of breath. The patient has no past medical history, has not traveled recently, and denies intravenous drug abuse. He is up to date on vaccines, including the COVID-19 vaccine. He received his second dose of the mRNA vaccine three days previously. His vital signs are: temperature 101°F, heart rate 115 beats per minute, blood pressure 107/85 mmHg, respiratory rate 32 breaths per minute, and SpO₂ 94% on room air. The physical exam reveals flushed skin, mild jugular vein distention, clear oropharynx, clear lung sounds bilaterally, tachycardia, no rashes, soft abdomen, and no lower extremity edema. What is in the differential diagnosis? What tests should be considered? What are the treatment options? What is the probable disposition?

Epidemiology

The exact prevalence of myocarditis is unknown. Myocarditis can be an elusive disease. Confirming the diagnosis is invasive and expensive, and symptoms often are misdiagnosed as a different disease process.^1,6

It is estimated that the incidence of myocarditis is between 1.5 and 1.8 million cases worldwide annually.^1,5,6 The prevalence and death rates for myocarditis have increased over the past few decades, with a 75.4% and 42.8% rise, respectively, since 1990.⁷ This surge could be the result of various factors, including the existence and dissemination of new pathogens that cause myocarditis (with COVID-19 as an example), the use and development of vaccines and drugs that trigger myocarditis, or the development of accessible, less invasive diagnostic techniques that are able to better detect myocarditis.¹ Regardless, especially amid the SARS-CoV-2 pandemic, a further increase in the reported incidence of myocarditis is expected.¹

In general, the majority of the patients diagnosed with myocarditis were men, found to be between 60% and 80% of reported cases.^1,6-8 However, it also has been noted that the clinical presentation in women may be more subtle and, thus, could lead to potential missed diagnoses and underreported incidence.¹ Additionally, most patients with myocarditis were found to be young, with the median age at presentation noted to be approximately 34 years.⁸ As such, myocarditis is a growing concern throughout the world, and furthermore has been linked to sudden cardiac deaths in young adults at rate of around 10%.⁹ Thus, further investigation into myocarditis is necessary to improve health outcomes and reduce morbidity and mortality.

Pathophysiology

The exact mechanism of acute myocarditis still is unclear. However, this disease commonly is recognized as an inflammatory cardiac injury, triggered by a variety of infectious, autoimmune, or toxic sources.^1,10,11 The potential etiologies are summarized in Table 1. The proposed mechanism of myocarditis suggests that two components, direct cell damage and T-lymphocyte mediated cytotoxicity, induce cardiac cell injury and death via a dysregulated immune response.^5,11 In the setting of viral infection, receptors on cardiac muscle cells allow for viral entry and subsequent replication within myocardial tissue.^3,6,12,13 This leads to destruction of these cells through cytotoxicity, both from the pathogen and the host immune system, leading to tissue necrosis.^3,6,11-13

Other triggers, such as toxins or autoimmune conditions, may function in a similar way, with oxidative stress leading to cardiac cell injury.^1,5 Regardless, immune-mediated activation of pro-inflammatory cells, such as B and T cells, triggers additional destruction of cardiac tissue through increased circulation of intracellular antigens, autoantibody creation, and cytokine storm.^3,6,11-13 This process functions in a cyclical fashion, as increased destruction triggers more immune activation, eventually leading to diffuse myocardial necrosis and cardiac dysfunction.^3,6,11-13

Viruses

The true incidence of viral myocarditis is unknown, given the difficulty in establishing a diagnosis. A variety of pathogens are known to trigger myocarditis, with variation based on time-period, location, and differences in preventative medicine access. These pathogens also have differences in duration and can be acute or chronic depending on the specific virus and its inflammatory mediated effects.

In the United States in the 1990s, adenoviruses and enteroviruses were found to be the most common cause of myocarditis and dilated cardiomyopathy in all patients.¹⁴ These viruses are thought to be primary cardiotropic and can cause both acute myocarditis and chronic myocarditis, leading to dilated cardiomyopathy.⁴

Parvovirus B19 and human herpesvirus 6 also are common known causes of myocarditis and, if cardiac tissue is involved, likely lead to progression to chronic dilated cardiomyopathy.^4,8 Additionally, viruses such as human immunodeficiency virus (HIV), hepatitis C, dengue fever, rubeola, influenza A, and influenza B can trigger myocarditis via immune system activation and inflammatory overdrive.^1,8 Lastly, coronaviruses, specifically SARS-CoV-2, are emerging as a prominent trigger of acute myocarditis.^5,11

Bacteria

Bacterial pathogens, such as Corynebacterium diphtheriae, streptococci, meningococci, Salmonella, Borrelia burgdorferi, Mycoplasma pneumoniae, Chlamydia psittaci, and Shigella, are known to be etiologies of myocarditis.¹ A wide array of pathogens can trigger myocarditis, and the presentation can vary significantly in severity and time course. In this sense, any patient with evidence of infection and/or symptoms should be evaluated for myocarditis, since many different pathogens can trigger the inflammatory cascade within cardiac tissue.

Trypanosoma cruzi is a major myocarditis-causing pathogen historically confined to Central and South America. Because of globalization, this pathogen has started to migrate to other continents, and infection has begun to reach worldwide.¹ Other frequent etiologies of myocarditis in Latin America include measles, meningococcal meningitis, HIV, dengue fever, and diphtheria, while in Japan, hepatitis C is a more common cause.^1,15 Reports from countries in Africa suggest that HIV, Trypanosoma cruzi, and Shigella are some of the most common causes of myocarditis on this continent.¹ Thus, travel history is an important component when evaluating for myocarditis. However, because of migration and globalization, pathogens originally endemic to certain areas still are capable of causing infection and subsequent myocarditis outside of their endemic locations.

Toxins

Many medical treatments and toxins have been implicated as etiologies for myocarditis. These presentations can be acute and chronic depending on the insult.¹⁶ The drug classes most commonly associated with myocarditis include antipsychotics, immune checkpoint inhibitors, and vaccines.¹⁷

Myocarditis induced by immune therapy inhibitors, such as nivolumab, was found in 1.14% of treated patients within one month of treatment and was observed to have a higher mortality risk than myocarditis triggered by other toxins.^17,18 Clozapine-associated myocarditis was found to be highest within one month of initiation of treatment, with an incidence varying from 0.06% to 3.88% across studies, and was the most represented drug among the antipsychotic class to cause myocarditis.^17,19

Other categories of drugs are known triggers of myocarditis, including psychiatric medications, recreational drugs, heavy metals, antineoplastic agents, and antibiotics.^1,16 Psychiatric medications with this risk include tricyclic antidepressants, benzodiazepines, and phenothiazine.^1,16 Recreational substances, such as cocaine, amphetamines, and alcohol, also are known to cause toxic myocarditis.^1,16 Other agents include heavy metals, such as ferrous sulfate, lithium, lead, arsenic, and copper, as well as many different antineoplastic therapies, including 5-fluorouracil, anthracyclines, cyclophosphamide, and tyrosine kinase inhibitors.^1,16 Antibiotics, such as penicillin, ampicillin, azithromycin, cephalosporins, and tetracyclines, also may trigger inflammation within heart muscle. Lastly, drugs such as dobutamine, dopamine, ephedrine, epinephrine, norepinephrine, and phenylpropanolamine have been shown to cause myocarditis.¹⁶ It is important to note that toxin-induced myocarditis must be differentiated from other causes of myocarditis, such as infectious, in clinical practice.

Myocarditis also has been linked with vaccines. Prior to the SARS-CoV-2 pandemic, the smallpox vaccine was the one most associated with myocarditis. Incidences of myocarditis were reported primarily in younger patients and occurred within 30 days of vaccination, most often within the first two weeks.^17,20 Vaccine-associated myocarditis appeared to have the lowest mortality risk among categories of common toxic myocarditis. Most cases typically are self-limiting.^17,21

COVID-19 and Vaccines

During 2020 and 2021, the coronavirus SARS-CoV-2, which produces the disease known as COVID-19, emerged as a cause for myocarditis.^11,22 Between March 2020 and January 2021, it was found that patients diagnosed with COVID-19 had a 0.146% absolute risk of developing myocarditis, a risk that was 15.7 times greater than patients without COVID-19.²² In that same period, the number of inpatient encounters for myocarditis increased by 42%. This abrupt rise correlated with spikes in diagnosis and hospitalization from COVID-19.²² While COVID-19-induced myocarditis is an uncommon occurrence overall, it nevertheless should be considered clinically when a patient with COVID-19 infection presents with chest pain, shortness of breath, or elevated cardiac biomarkers.

Myocarditis has been reported as a rare adverse event after the COVID-19 mRNA vaccination.^22,23 The risk for developing myocarditis was found to be highest within one week of the first dose and second dose of both COVID-19 mRNA vaccines.²⁴ This risk was most prevalent in males ages 12-29 years. The majority of cases were mild and self-limiting, requiring hospitalization for zero to four days.^5,23 The risk of myocarditis following COVID-19 vaccination was found to be one-fourth the risk of myocarditis following COVID-19 infection.²⁴ In addition, the average hospitalization course for myocarditis related to COVID-19 vaccination was found to be shorter than the hospitalization course for COVID-19-associated myocarditis.²⁴

Risk Factors

Various factors play into the development and prognosis of myocarditis. Young adult males make up most cases of myocarditis.^1,7 Although this may be caused by reporting bias, it is nevertheless important to consider that sex and age may be risk factors.¹ Underlying autoimmune conditions tend to have an increased propensity for myocarditis. Social factors, such as alcohol abuse, illicit drug use, and travel, may increase the risk of developing myocarditis.^1,16,17

Presentation

Signs and Symptoms

Myocarditis can be a very elusive diagnosis. Patients may present acutely with fever, chest pain, and shortness of breath or may have a more indolent course with vague symptoms similar to a viral prodrome, such as malaise and myalgias.

Per the European Society of Cardiology, there are three distinct profiles that can be used to classify myocarditis.^6,13 First, myocarditis can present as an acute coronary syndrome-like picture, with chest pain in the absence of diagnostic evidence of coronary artery disease.^6,13 The second described clinical profile includes symptoms of new-onset or worsening heart failure over two weeks to three months, with new or worsening shortness of breath, peripheral edema, chest pain, and fatigue in the absence of known heart failure or coronary artery disease.^6,13 Lastly, myocarditis can present as a life-threatening sepsis, cardiogenic shock, or arrhythmia with palpitations, chest pain, hypotension, and syncope in the absence of heart failure, coronary artery disease, or other known cardiac cause.^6,13

When patients present with the third profile, it is prudent to take measures to distinguish myocarditis from sepsis. This is crucial because aggressive fluid resuscitation, the treatment for sepsis, is known to worsen myocarditis and can even cause cardiogenic shock.¹¹

Ultimately, for all of these symptom profiles outlined in Table 2, it is critical to obtain a detailed history, including recent vaccinations, preceding infections, past medical history, travel history, medication use, and substance use, to assess for myocarditis as part of the differential diagnosis.

The symptoms of myocarditis, such as fatigue, shortness of breath, chest pain, peripheral edema, and tachycardia, are nonspecific. However, the presence of these symptoms and a high-risk history should increase clinical suspicion for myocarditis.^6,11 Frequently, the viral prodrome, such as in COVID-19, may occur up to two weeks prior to cardiac symptoms.^6,10 Recent initiation of drug therapy, particularly those medications known to cause myocarditis, or vaccination also may indicate that further cardiac workup is necessary.^6,17

Diagnostic Tools

Clinical presentation and noninvasive techniques can be helpful in identifying myocarditis and narrowing the differential diagnosis. Definitive diagnosis can be challenging, given the invasive nature of the gold standard testing.^3,5,6,11 When a patient presents with signs and symptoms concerning for myocarditis, the initial assessment should include serum troponins, brain natriuretic peptide (BNP), an electrocardiogram (ECG), and echocardiogram.^5,6,11 Elevated troponin was found to be present in the majority of patients presenting with acute myocarditis, and, thus, negative serial cardiac troponins significantly decrease the likelihood of acute myocarditis.^6,11

For postvaccination myocarditis, troponins were found to peak around three days postvaccination.^5,25 An elevated BNP level, while not diagnostic, can suggest heart failure or ventricular dysfunction and may aid in risk stratifying these patients.⁶ Inflammatory markers, such as erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), procalcitonin, and lactate, and a complete blood count with differential also can be collected for evaluation and may provide useful information regarding etiology.^5,6,11 In myocarditis, inflammatory markers typically are elevated but are nonspecific.¹³

A 12-lead ECG should be performed in all patients with possible myocarditis.^6,13 ECG changes may be nonspecific and variable, but findings such as diffuse ST-segment elevation, ST-segment depression, PR depression, T-wave inversions, sinus tachycardia, atrioventricular (AV) block, and even ventricular arrhythmias are possible in myocarditis.^3,5,6,11 Diffuse ST-segment elevation in a concave pattern may be more specific for myocarditis. However, a normal ECG does not exclude myocarditis.^6,11,13 These findings are demonstrated in Figures 1-3.

Transthoracic echocardiogram (TTE) should then be performed in patients with suspected myocarditis. It is important to note that this is not diagnostic but more so to rule out other possible cardiac pathologies, such as valvular abnormalities or regional wall motion abnormalities. The TTE also can be used to assess ventricular function, which aids in risk stratifying this patient population and provides serial monitoring during hospitalization.^6,13 Echocardiogram findings in myocarditis are nonspecific and may include increased wall thickness, chamber dilatation, pericardial effusion, wall motion abnormalities, and reduced ejection fraction. Some of these are demonstrated in Figures 4-7.^3,11,13

Given the vague presentation of these patients, a multitude of other tests may be indicated to rule out other pathology. Computed tomography (CT) angiography may be considered to rule out pulmonary embolism or other etiology.⁶ Percutaneous coronary angiography may be performed if there is a high level of concern for ischemic cardiac dysfunction.⁶ A chest radiograph also may be performed to rule out a variety of pathologies. In patients with myocarditis, a chest radiograph may be negative or show cardiomegaly, vascular congestion, or pleural effusion.⁶

Cardiovascular magnetic resonance imaging (MRI) is the noninvasive gold-standard test available for myocarditis.³ Cardiovascular MRI is indicated in patients presenting with findings concerning myocarditis after troponins, BNP, ECG, echocardiogram, and other components of the initial evaluation have been performed.¹⁰ When using cardiovascular MRI, various components, including inflammatory hyperemia, edema, necrosis or scarring, contractile dysfunction, and pericardial effusion, are examined to assess for myocarditis.²⁶ These features are considered as part of a consensus statement from the European Society of Cardiology Lake Louise Criteria for the diagnosis of myocarditis.^13,26 Of the listed components, the presence of two out of the three criteria of edema, hyperemia, and necrosis on cardiovascular MRI is diagnostic of active myocarditis.^13,26 A cardiovascular MRI finding of myocardial edema is indicative of reversible injury and inflammation, is most prominent in the setting of acute myocarditis, and can predict a favorable prognosis in these patients.

Myocardial hyperemia, another feature of inflammation seen on cardiovascular MRI, was found to be less prevalent in patients younger than the age of 40 years and may be associated with chronic symptomatology and persistent dysfunction, although more studies need to be done to assess prognosis.

Finally, the finding of necrosis or scarring on cardiovascular MRI is described as irreversible injury and has been associated with increased disease severity and higher overall mortality.²⁶ Contractile dysfunction and/or pericardial effusion are considered supportive features of the Lake Louise Criteria and are listed to provide additional evidence for myocarditis and guidance on management.^13,26

Cardiovascular MRI can provide a detailed assessment of ventricular function and can provide information regarding the necessity of medication to treat underlying heart failure.²⁶ The detection of pericardial effusion on cardiovascular MRI additionally can guide any further treatment, depending on the size or significance.^13,26 Ultimately, the use of MRI in conjunction with the Lake Louise Criteria to diagnose myocarditis has been helpful in clinically stable patients and can serve as a noninvasive tool for assessment, treatment, and prognosis.^13,26 Some limitations of cardiovascular MRI include lack of availability, suboptimal timing during disease course, and inferior sensitivity compared to endomyocardial biopsy.^13,26

Endomyocardial biopsy (EMB) is the gold standard for definitive diagnosis of myocarditis.^{1,10,11,13,26} Compared to previously discussed tools for diagnostic imaging, EMB is the most invasive method for diagnosis, but it provides the most detailed information regarding the diagnosis and etiology.¹³

Using EMB, multiple samples are obtained and analyzed through examination of histology, immunohistochemistry characterizing inflammatory infiltrate, and viral genome analysis.^4,13 The typical histological finding for acute myocarditis is lymphocytic infiltrates with cardiomyocyte necrosis. Depending on etiology, histology can show viral nucleic acids, granulomas, or eosinophils.^4,6 Given the patchy presentation of myocarditis, samples from multiple different locations on the heart are required to enhance accuracy.^4,13 Although there are risks in obtaining EMB given its invasive nature, its use is recommended for patients who are hemodynamically unstable, patients presenting with symptoms for more than three months, or patients who have failed usual medical therapy.^4,6,13

Treatment and Disposition

Key principles for the management of myocarditis involve supportive care and treatment of underlying pathology, depending on the clinical presentation of the patient.^6,12,13 When present, patients should be treated with guideline-directed medical therapies for concomitant acute heart failure or arrhythmias.^27,28

Once myocarditis is identified, certain findings can be prognostic and can help guide disposition. For instance, the presence of troponin elevations has been shown to confer a fivefold increase in likelihood of intensive care unit (ICU) admission, ventilation requirement, ventricular arrhythmias, and, subsequently, increased mortality.^29,30 Patients presenting with a left ventricular ejection fraction of less than 50% also were at risk of death both during admission and within the five-year follow-up period.⁸ Additionally, any patient with symptoms of hemodynamic compromise or cardiogenic shock at initial presentation had increased short- and long-term mortality.²

Other factors associated with increased mortality include reduced creatine clearance, age older than 50 years, male gender, and ventricular tachycardia.³¹ Conversely, it was found that patients with minimal rises in troponin and BNP, preserved ejection fraction, hemodynamic stability, and the absence of persistent arrhythmia had a better prognosis with a lower risk of persistent left ventricular dysfunction and mortality.^2,8,29

In the hemodynamically unstable with myocarditis confirmed by EMB, the patient should be admitted or transferred to the ICU.^13,27 Per guidelines from the 2021 European Society of Cardiology and supported by the American College of Cardiology, patients undergoing acute heart failure should receive intravenous loop diuretics if there is evidence of fluid overload, inotropic agents and/or vasopressors if there are signs of persistent hypoperfusion or end organ damage, and supplemental oxygen or noninvasive positive pressure ventilation if there is evidence of hypoxemia.²⁸

The pressor of choice for fulminant myocarditis with shock is norepinephrine secondary to it being less likely to cause arrhythmias and having improved outcomes.^32-34 For cardiogenic shock refractory to conservative management, mechanical circulatory support such extracorporeal membrane oxygenation (ECMO) may be necessary. For respiratory distress, airway support with noninvasive positive pressure ventilation or intubation may be necessary. There are no specific ventilation strategies recommended for myocarditis at this time.^13,27,28,33 Cardiac transplant and a ventricular assist device may be indicated if heart failure persists.^13,28,33,34

Hemodynamically stable patients with myocarditis should be admitted to the hospital for continued monitoring during their disease course.¹³ The rationale for admitting these patients is that they are at increased risk for arrhythmias, including lethal arrhythmias.¹³ Patients in this category also should receive guideline-directed medical therapy, including diuretics, angiotensin converting-enzyme inhibitors, and aldosterone antagonists, to optimize cardiac outcomes. However, beta blockers, calcium channel blockers, and other medications with negative ionotropic properties should be avoided.^10,13,28,34 Guidelines also suggest avoiding nonsteroidal anti-inflammatory drugs (NSAIDs) in fulminant myocarditis since they may lead to sodium retention and renal dysfunction.³⁴

Patients with evidence of arrhythmia should receive appropriate treatment consistent with current guidelines, including anticoagulation and antiarrhythmic therapy.¹³ A temporary pacemaker or cardioverter defibrillator implantation may be indicated in accordance with clinical recommendations; however, this can be deferred until after recovery.¹³

There is very little evidence for myocarditis-specific therapies.^6,13 Antiviral therapies are not necessarily indicated, even in viral myocarditis, because they have not been shown to have a benefit. Current recommendations, while limited, are to manage the underlying infection per active guidelines. For COVID-19 myocarditis, this includes antivirals such as remdesivir, steroids, and possibly convalescent plasma and monoclonal antibodies.³⁵

One thing to consider is that there are case reports of bradycardia associated with remdesivir, which may worsen underlying cardiac dysfunction in patients with myocarditis.³⁶

There is no literature of the need for or use of antivirals in vaccine-induced myocarditis. If there is a question, infectious disease physicians can be consulted to consider the necessity.^4,6,13 Intravenous immunoglobulin is not routinely recommended because of ineffectiveness in controlled trials.^6,11,13 Immunoglobulin has only been shown to have some benefit in parvovirus-induced myocarditis.³⁴ Immunosuppressive therapy is not currently recommended, especially for the treatment of viral myocarditis.^3,6,11,13 However, in the setting of noninfectious, EMB-confirmed myocarditis, specifically giant cell myocarditis, refractory to conservative management, immunosuppressive therapy can be considered, given there are no contraindications.^10,13,34

In addition to supportive care and medical management, patients also should follow short-term lifestyle modifications. Exercise should be avoided until the disease has resolved, and athletes should be evaluated prior to returning to sports.^4,6,13,27 Alcohol and tobacco should be avoided, and physical therapy and/or cardiac rehabilitation could be considered depending on the patient’s activity level and function.⁶ Patients should follow up as outpatients with a cardiologist after discharge, and, given normalized cardiac enzymes after discharge, receive noninvasive serial assessment. If troponins remain elevated or ventricular function appears to decrease, EMB could be considered, given potential worsening of the disease process.¹³

Summary

Myocarditis is a disease entity that is quite elusive. It has a variable time course, presentation, and severity. Since the onset of the SARS-CoV-2 pandemic, this disease has steadily increased in incidence, morbidity, and mortality. This condition is particularly relevant to study in the emergency medicine setting, since the acute presentation of myocarditis must be effectively differentiated from other disease processes that present similarly. Initial diagnostic testing, such as serum troponins, BNP, ECG, and echocardiogram, can be helpful, but cardiovascular MRI and/or EMB are the best options for definitive diagnosis.^3,6,13,26

Treatment primarily focuses on the management of complications, such as acute heart failure or arrhythmia, and avoidance of exacerbating factors, such as exercise, drug use, or triggering medications.^{6,13,27,28,34} After discharge, patients should receive appropriate follow-up and monitoring for return to baseline functioning. Finally, given the rise in prevalence of myocarditis, more studies are needed to further investigate this condition and create better guidelines for diagnosis, disposition, and treatment to optimize patient outcomes and resource utilization.

Case Conclusion

A 25-year-old male presents with chest pain, fatigue, and shortness of breath. The patient has no past medical history, has not traveled recently, and denies intravenous drug abuse. He is up to date on vaccines, including the COVID-19 vaccine. He received his second dose of the mRNA vaccine three days prior. His vital signs are: temperature 101°F, heart rate
115 beats per minute, blood pressure 107/85 mmHg, respiratory rate 32 breaths per minute, and SpO₂ 94% on room air. The physical exam reveals flushed skin, mild jugular venous distention, clear oropharynx, clear lung sounds bilaterally, tachycardia, no rashes, soft abdomen, and no lower extremity edema.

For this patient, the biggest concern is myocarditis triggered by COVID-19 mRNA vaccination. Given his symptoms and physical exam, it would be appropriate to order serum troponins, BNP, and inflammatory markers. An ECG should then be obtained. This patient should be monitored for arrhythmias. Given that this typically is a self-limited disease that usually resolves in two to three days, a short observation stay or close monitoring likely is appropriate, as long as the patient remains hemodynamically stable and without signs or symptoms of heart failure.

When the patient is discharged, he should be given strict return precautions to come back for worsening shortness of breath, edema, increased pain, or palpitations. The patient also should be instructed to avoid strenuous exercise, alcohol, tobacco, drugs, and other cardiac-toxic medications. Given the etiology and presentation, this patient has a good prognosis for full recovery.

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