Mr. C is a 43-year-old man with a history of hypertension, dyslipidemia, and impaired fasting glucose who was admitted to the emergency department with sudden-onset, severe, stabbing, left anterior chest pain that woke him at 4 a.m. Initially thinking the pain could be due to heartburn, he took omeprazole empirically and tried to go back to sleep. However, the pain persisted with subsequent radiation down both arms, which prompted him to go to the emergency department. In the days before this episode, he reported that he had a “cold” with productive cough and malaise, but no fevers or chills; the sputum was clear, nonpurulent, and nonbloody. He said that his chest pain was somewhat better sitting up, and he did not report pleuritic chest pain.
Physical exam showed a well-nourished man in mild distress. His heart rate was 80 beats per minute, and his blood pressure was 133/84 mm Hg. Remaining vital signs were within normal limits and stable. Heart auscultation revealed normal S1 and S2 with no murmurs, rubs, or gallops; there was no increased jugular venous distention. Chest wall was not tender to palpation. Chest auscultation revealed normal bilateral respiratory vesicular sounds with no adventitious sounds. His peripheral pulses and blood pressures were equal and symmetric bilaterally.
Notable initial labs showed a white blood count of 7.59 cells/mm3, a creatinine level of 0.93 mg/dL, a potassium level of 4.4 mEq/L, a troponin level of 1.93 mg/dL at 7:32 a.m., and a subsequent troponin level of 4.85 mg/dL at 10:10 a.m. Creatine kinase (CK) level was 208 mg/dL, and CK-MB level was 8.6 mg/dL at 7:32 a.m. Liver function tests showed an elevated aspartate aminotransferase (AST) level at 76 U/L and an elevated alanine aminotransferase (ALT) level at 88 U/L with normal total bilirubin and alkaline phosphatase levels. Electrocardiogram (ECG) on arrival showed normal sinus rhythm with diffuse ST-segment elevation and concave-up morphology. Chest X-ray was normal. A stat echocardiogram was normal.
The patient received 324 mg of aspirin on presentation and was admitted as an inpatient to the medical telemetry service for observation. The patient's pain subsided within an hour after presenting to the emergency department. A diagnosis of myopericarditis was made based on clinical and ECG findings. The patient was started on oral ibuprofen, 800 mg 3 times per day, and oral colchicine, 0.6 mg twice daily. His serum troponin level peaked at 4.93 ng/mL. A cardiac CT was done, showing normal cardiac chamber size, normal aortic root, and no pericardial effusion; coronary anatomy was normal with an AJ-130 coronary calcium score of 0. The CT did show right lower-lobe centrilobular lung nodularity and peribronchial nodular consolidation and atelectasis consistent with mild bronchopneumonia.
Myopericarditis is defined as pericarditis with some degree of concurrent myocardial inflammation (e.g., myocarditis). Although often characterized separately in the literature, pericarditis and myocarditis usually coexist to some degree in clinical practice. However, their respective involvement is not typically equivalent, which is what gives rise to clinical presentations that are predominantly pericarditic or myocarditic. As such, the term, “myopericarditis” specifies a primarily pericarditic syndrome and the term “perimyocarditis” specifies a primarily myocarditic syndrome (1).
Etiology and pathogenesis
Myocarditis and pericarditis have similar causes; thus, it is likely that host factors (e.g., genetic, immunologic, and hormonal) influence the dominant clinical syndrome in a given patient. The 3 general etiologic groups are idiopathic, infectious, and immune-mediated (2). Viral infections are the most common cause in the developed world. The viruses typically seen in North America are coxsackievirus, adenoviruses, cytomegalovirus, Epstein-Barr virus, influenza, hepatitis A and C, varicella zoster, and parvovirus B19 (2).
Bacterial causes are less common, with tuberculosis being the most important worldwide, particularly in association with HIV. There have been case reports implicating Campylobacter jejuni and Shigella. There have also been rare cases associating myopericarditis with Neisseria meningitides, Chlamydophila pneumoniae, streptococcal pharyngitis or tonsillitis, and even community-acquired bacterial pneumonia (2).
Myopericarditis also occurs in association with immune-mediated diseases such as vasculitis (principally giant-cell arteritis), systemic lupus erythematosus, adult-onset Still's disease, and inflammatory bowel disease. It has also been described in patients exposed to different drugs, including antineoplastic agents (e.g., 5-fluorouracil), phenytoin, antipsychotics (e.g., clozapine), and mesalazine. Last, it has been well described in association with the vaccinia (smallpox) vaccine and rarely in association with other vaccines (such as diphtheria, tetanus, and polio) (2).
A typical viral infection may involve direct cytolytic and cytotoxic-mediated inflammation in the pericardium and myocardium and/or indirect injury through immunopathic mechanisms such as molecular mimicry and epitope spreading. These immune mechanisms may result in continued myopericardial inflammation even after resolution of viremia. They may also explain the pathogenesis of vasculitis-connective tissue disease, inflammatory bowel disease, radiation, and drug-induced myopericarditis (1, 2).
Myopericarditis is more common in younger male patients. Patients will often report a recent or concurrent respiratory or gastrointestinal illness with associated fever and myalgias (1-3). The clinical presentation is often proportional to the extent and pattern of myocardial involvement, with many cases being subclinical or obscured by the systemic symptoms of the viral illness. Typical manifestations may include positional or pleuritic chest pain, fatigue, decreased exercise tolerance, or palpitations. In most cases, the symptom pattern does not help differentiate between simple pericarditis and myopericarditis. Furthermore, it may be difficult to differentiate myopericarditis-related chest pain from ischemic chest pain (1). Physical examination may be normal in most patients, although physical findings may be proportional to the degree of organ involvement: systemic inflammation (fever), pericardial fluid (friction rub), and acute heart failure (jugular venous pressure, gallop, edema, rales, etc.).
Myopericarditis is diagnosed when the patient satisfies the diagnostic criteria for pericarditis (Table 1) and also demonstrates evidence of myocardial inflammation (i.e., elevated cardiac enzymes or inflammation seen on cardiac MRI). In addition, the patient should not have evidence of significant myocardial dysfunction on echocardiogram (which would be more suggestive of perimyocarditis) (2).
Electrocardiographic (ECG) changes are often seen in myopericarditis due to associated epicardial or myocardial injury. The evolution of the ECG in myopericarditis is similar to that of simple pericarditis and begins with diffuse ST-segment elevation and PR-segment depression, followed by ST and PR normalization, and then finally diffuse T-wave inversions. ECG changes that are more specific to myopericarditis include convex ST morphology, localized ST elevation (inferolateral or anterolateral), T-wave inversions before ST-segment normalization, reciprocal changes, new Q waves, or QT prolongation. Cardiac arrhythmias, such as supraventricular or ventricular ectopy and nonsustained ventricular tachycardia, are also more common in myopericarditis (<10% vs. >60%) (1-3).
Cardiac enzymes (CK-MB fraction or troponin I or T) may be elevated in myopericarditis. Troponin elevation seems to be more common in myopericarditis, and the magnitude often correlates to the degree of myocardial injury. As a reference, troponin has a reported sensitivity of 34% and a positive predictive value of 90% in myocarditis (1). The pattern of troponin elevation typically either involves a slight elevation followed by rapid clearance or a more significant elevation followed by a more gradual clearance similar to that of an acute coronary syndrome pattern. In few cases (<5%), the troponin can be persistently elevated for several weeks, representing sustained myocardial injury (3). Although signifying myocardial injury, troponin elevation in myopericarditis is not independently associated with an adverse prognosis (1).
The echocardiogram in myopericarditis is usually normal. Pericardial effusions are less common in myopericarditis than in acute pericarditis. In some cases, the pericardium may demonstrate increased echogenicity indicating pericardial inflammation. Significant myocardial dysfunction is typically not seen with myopericarditis, and its presence should raise suspicion of a more myocarditis-dominant syndrome (i.e. perimyocarditis) (2).
Special diagnostic considerations
Cardiovascular magnetic resonance
Cardiovascular magnetic resonance (CMR) is useful both in diagnosing pericarditis and in detecting myocardial inflammation. As a result, CMR can be used to confirm the diagnosis of myopericarditis. MRI imaging techniques for myocardial inflammation consist of T2-weighted imaging in assessing myocardial edema, T1-weighted imaging pre- and post-contrast administration to evaluate for hyperemia, and late gadolinium enhancement. Myocardial inflammation can be confirmed if 2 of the 3 MRI imaging techniques are positive (2). Older studies reported a sensitivity of 84% to 100% and a specificity of 90% to 100%, while a recent study comparing CMR with the endomyocardial biopsy reported a diagnostic sensitivity, specificity, and accuracy of 81%, 71%, and 68%, respectively, for acute myocarditis (1, 4).
Although endomyocardial biopsy is considered the gold standard for diagnosing myocarditis, there are only a few indications for performing it. Experts currently recommend a biopsy for patients with subacute or acute heart failure refractory to medical therapy; decreasing ejection fracture despite optimal medical therapy; hemodynamically significant arrhythmias; or heart failure associated with a concurrent rash, fever, or peripheral eosinophilia, history of collagen vascular disease, or suspicion of giant-cell myocarditis (2).
Experts do not routinely recommend serological studies in the setting of uncomplicated pericarditis or myopericarditis. The vast majority of pericarditis and myopericarditis cases in immunocompetent hosts from developed countries are viral or idiopathic in origin. Furthermore, a viral cause for myocarditis can only be proven if the virus is detected within altered myocardium by histopathology (5). As a result, a comprehensive workup is unlikely to add value to the patient's care and would add unnecessary cost. It seems reasonable to follow the general guidelines for pericarditis, which recommend an extensive etiologic workup in higher-risk patients with fever, subacute onset, immunosuppression, trauma, oral anticoagulant therapy, or severe pericardial effusion (4). In addition, patients in whom conservative therapy fails should be considered for more exhaustive workup, including serologic studies.
In certain patient populations, the clinical presentation of myopericarditis can be difficult to differentiate from that of an acute coronary syndrome. Clinicians should thus consider an invasive or noninvasive ischemic workup for patients at risk for ischemic heart disease. Patients with a high pretest probability for obstructive coronary artery disease should undergo cardiac angiography. Patients with a low to intermediate pretest probability for coronary artery disease should be considered for a less invasive approach, such as coronary computed tomography angiography (6).
Prognosis and risk assessment
In a recent systematic review with up to 31 months of follow-up, authors demonstrated a favorable long-term prognosis for myopericarditis. The reported pericardial complications seen with simple pericarditis, such as recurrent pericarditis, cardiac tamponade, and constrictive pericarditis, were exceedingly rare (7). The overall mortality rates reported in this review were also low, with only 3 reported deaths out of 389 patients followed, and only 1 study out of 8 reporting any deaths associated with myopericarditis. In those cases, all 3 deaths occurred during the initial hospitalization; 1 death resulted from cardiac tamponade and the other 2 resulted from sudden cardiac death. The authors concluded that in the absence of significant myocardial dysfunction, the presence of myocardial involvement in pericarditis (also known as myopericarditis) is not a negative prognostic marker.
When to admit
Experts recommend initial hospitalization for all patients with suspected myopericarditis (2). The primary objectives in evaluating a patient with suspected myopericarditis should be 1) establishing the diagnosis, 2) excluding an acute coronary syndrome, and 3) assessing for significant left ventricular dysfunction or other high-risk features. Once the diagnosis of myopericarditis has been established and no high-risk features have been found (such as ventricular arrhythmias or significant left ventricular dysfunction), the patient can be safely discharged.
Treatment and follow-up
Given that most myopericarditis cases are idiopathic or viral in origin, the current evidence does not support any specific therapies aimed at the underlying causal agent. The consensus recommendation is to treat myopericarditis similarly to acute pericarditis, using anti-inflammatory therapies. Current recommendations are generally based on the 2004 European Society of Cardiology guidelines (8). NSAID regimens include ibuprofen, aspirin, or indomethacin and are summarized along with other treatments in Table 2. NSAIDs are generally administered over several weeks at therapeutic doses and then gradually tapered. C-reactive protein measurements can be used to predict a higher rate of recurrence and to monitor disease progression while guiding therapy duration (11). In patients with contraindications to NSAID therapy, corticosteroids can be used as a second-line agent but are generally tapered more gradually. Colchicine can be used as an adjunct to NSAID therapy and has been shown to reduce symptom duration and rate of recurrence in pericarditis (10).
Currently there is insufficient evidence to support using colchicine in myopericarditis; however, it seems reasonable to consider on an individual basis. Patients at high risk for gastrointestinal bleeding complications (history of peptic ulcer disease, advanced age, concurrent anticoagulation) should be prescribed acid prophylaxis. In cases where there is significant left ventricular dysfunction (e.g., perimyocarditis), the patient should be concurrently treated with conventional heart failure methods and expert cardiology consultation. Sudden cardiac death after strenuous exercise is a rare but observed complication of pericarditis and myopericarditis. Accordingly, experts generally recommend restricting patients from physical exercise for at least 6 months after a myopericarditis diagnosis (2, 7).
Back to the case
Mr. C was discharged on hospital day 2 on a course of oral ibuprofen, 800 mg, 3 times daily for 2 weeks, followed by a tapered course over 3 weeks, combined with oral colchicine, 0.6 mg, twice daily for 1 month, then tapered over 2 months. Omeprazole was continued. He was also treated with a 5-day course of azithromycin for community-acquired pneumonia. Given his history of hypertension, dyslipidemia, and impaired fasting glucose, he was advised to follow up with his primary care clinician to discuss his risk factors for metabolic syndrome. He was also instructed to obtain repeated liver function tests within 1 week on follow-up. He was seen 6 weeks after discharge and was in good condition with resolution of his symptoms and no recurrence.
Summary and recommendations
Although acute pericarditis is often associated with some degree of myocardial involvement, it is important to recognize the presence of myocardial injury in pericardial syndromes (e.g., myopericarditis), due to the increased risk of ventricular arrhythmias and left ventricular dysfunction. Patients with myopericarditis should be initially hospitalized to establish the diagnosis, exclude cardiac ischemia, and monitor for complications. It is often difficult to differentiate myopericarditis from an acute coronary syndrome; therefore, appropriate patients should undergo an ischemic workup prior to discharge. Coronary computed tomography angiography may be a cost-effective and safe alternative to invasive angiography in patients with a low to intermediate pretest probability for coronary disease. Myopericarditis can be treated in the same fashion as acute pericarditis and generally has an excellent prognosis with an extremely low mortality rate. Given the risk of sudden cardiac death, patients should be restricted from exercise for at least 6 months after their diagnosis.