Myopericarditis

Article written and reviewed by Dr Luca Moretti

Myopericarditis is an inflammatory syndrome in which the clinical presentation is dominated by pericarditis and limited myocardial involvement coexists, documented by elevation of biomarkers of myocardial injury, without new ventricular dysfunction; cardiac magnetic resonance can characterize the involvement. In traditional clinical terminology, left ventricular function remains preserved and no new global or regional abnormality appears; if myocardial injury becomes predominant and causes dysfunction, the condition is better defined as perimyocarditis. The distinction describes a biological continuum but retains value for prognosis, monitoring, anti-inflammatory therapy and restriction of exertion.

The presence of troponin turns pericarditis into a myopericardial process only when the context is consistent and alternatives have been considered. A patient with positional pain, a friction rub or diffuse ST-PR changes and preserved function represents the classic phenotype, whereas pressure-like pain with territorial changes requires priority exclusion of acute coronary syndrome, coronary dissection, Takotsubo syndrome and pulmonary embolism. The label myopericarditis must therefore not become a shortcut for every case of chest pain with positive troponin and non-obstructive coronary arteries.

Incidence is difficult to estimate because it depends on the sensitivity of the troponin assay, use of CMR and the definition adopted. With high-sensitivity methods, modest myocardial injury is recognized more often in acute pericarditis, whereas in earlier periods it would have gone unnoticed. In registries from high-income countries, young adults, particularly men, with idiopathic or presumably viral disease predominate, but age, sex and prognosis change in autoimmune, neoplastic, tuberculous, drug-induced and immune-mediated etiologies.

Prospective cohorts show a generally favorable prognosis when ventricular function is preserved and there are no major arrhythmias or high-risk causes. Troponin elevation, considered in isolation, is not necessarily associated with late events and in most patients function remains or returns to normal. This observation does not, however, justify trivializing the initial phase, during which time-dependent diagnoses must be excluded and any transition toward a more severe myocardial phenotype recognized.

Etiology, Pathogenesis and Pathophysiology

In countries where tuberculosis and other specific infections are uncommon, many forms are classified as idiopathic or presumably viral. Enteroviruses, adenoviruses, parvovirus B19, herpesviruses, influenza, HIV and SARS-CoV-2 may be associated with myopericardial inflammation, but a prodrome or serology does not prove infection in the heart. Injury may result from the agent, the immune response or both, and microbiologic investigation should be guided by epidemiology, exposure and severity.

The visceral pericardium adheres to the surface of the heart and is not a biologically isolated compartment from the subepicardial myocardium. Cytokines, vascular mediators and immune cells may cross this continuity, producing pain and inflammation of the pericardial layers together with edema and focal injury of the outermost layers of muscle. This distribution explains frequent inferolateral subepicardial LGE and the possibility of elevated troponin with globally preserved function.

Innate immunity recognizes nucleic acids and damage signals, activates inflammasomes, interferons and complement, and recruits neutrophils, monocytes and macrophages; in subsequent days, T and B lymphocytes may eliminate the agent or prolong inflammation through mimicry and epitope spreading. If the response resolves, edema and pain regress; if it persists, subepicardial scar, recurrent pericarditis or more extensive myocardial involvement may remain.

Autoimmune and autoinflammatory diseases, including connective tissue diseases, vasculitides, Still disease and periodic syndromes, may involve the pericardium and myocardium simultaneously; systemic manifestations, recurrent course and response to other therapies help guide classification, but extracardiac and cardiac activity are not always parallel. Sarcoidosis, eosinophilic disease and giant-cell myocarditis should be considered when blocks, arrhythmias, dysfunction or a trajectory incompatible with uncomplicated idiopathic disease develop.

Drugs, vaccines, radiotherapy, checkpoint inhibitors and post-cardiac injury syndromes may produce a myopericardial phenotype through hypersensitivity, loss of immune tolerance or antigen release. Temporal association is informative but insufficient, especially for common exposures. Rash, eosinophilia, myositis, myasthenia or conduction disorders increase the probability of a specific mechanism and may radically change the urgency of biopsy and treatment.

Pain results from inflammation of the richly innervated parietal pericardium and is accentuated by friction between the layers and respiratory movements. Myocardial injury releases troponin without the circulating amount measuring anatomic extent linearly, because focal distribution, timing of sampling and individual kinetics alter the peak. Function remains preserved in the classic definition, but strain may reveal subtle abnormalities and requires interpretation in context.

Effusion and edema affect mechanics differently. A small effusion does not reflect the severity of myocardial injury, whereas rapid accumulation may impair filling and cause tamponade even without a large volume. Myocardial edema can temporarily alter conduction and refractoriness, explaining ectopy and ECG changes; new significant dysfunction, sustained arrhythmias or shock require the condition to be reclassified beyond uncomplicated myopericarditis.

Bacterial, tuberculous, fungal and neoplastic causes are less common in the typical phenotype of a young immunocompetent person but become more important in the presence of persistent fever, immunosuppression, large effusion, tamponade or failure to respond to therapy. In these settings, if accessible, the effusion should be studied with cytology, cultures and selected molecular analyses because empiric suppression of inflammation can alleviate symptoms while allowing the underlying cause to progress.

Clinical Manifestations

The dominant symptom is acute chest pain, often pleuritic and positional, which worsens with deep inspiration and recumbency and improves on sitting up or leaning forward. It may radiate to the shoulders and trapezius ridge and be associated with low-grade fever, asthenia and palpitations. These features increase the probability of pericarditis but are not absolute, and the presence of sweating, nausea or radiation to the arm does not reliably distinguish an inflammatory process from ischemia.

A respiratory or gastrointestinal prodrome in the preceding weeks is common, but its absence does not reduce the probability to zero and its presence does not prove a viral cause. History taking looks for new drugs, immunotherapy, autoimmune diseases, tuberculosis, neoplasms, renal failure, cardiac procedures, trauma and radiation; travel, infectious contacts and immunosuppression alter the weight of specific causes and the need for microbiologic samples.

On auscultation, a pericardial friction rub is highly suggestive but transient and poorly sensitive; its absence does not exclude the diagnosis. Tachycardia disproportionate to fever, an irregular pulse or bradycardia requires attention to electrical involvement. Blood pressure, perfusion, jugular veins and pulsus paradoxus are assessed so as not to miss tamponade or a form with dysfunction, while crackles, a third heart sound and edema are unexpected in classic myopericarditis and suggest a more substantial myocardial component.

Palpitations often result from premature beats or sinus tachycardia, but syncope, sustained ventricular tachycardia and advanced block do not belong to the benign profile and require intensive monitoring and etiologic reassessment. A normal ejection fraction does not eliminate electrical risk when CMR shows extensive or septal LGE; definition of the phenotype must therefore integrate electrical stability and mechanical stability rather than being limited to pain.

Mild dyspnea may accompany pain and effusion, whereas orthopnea, pulmonary edema, hypotension, oliguria or cold extremities indicate heart failure or tamponade and require a diagnosis other than uncomplicated myopericarditis. Progression may occur during observation and justifies serial testing in patients with substantial troponin elevation, dynamic ECG changes or equivocal echocardiographic findings; improvement in pain does not guarantee normalization of myocardial injury.

In children, pain may be difficult to describe and irritability, tachycardia, reduced feeding and dyspnea predominate; in adolescents the presentation more closely resembles that in adults. In older adults and immunosuppressed patients, fever and inflammatory markers may be modest, while a neoplastic, bacterial or tuberculous cause carries greater weight; rash, arthritis, lymphadenopathy, eosinophilia and muscle weakness point toward systemic disease.

Assessment of severity also considers the setting in which the patient can be observed. A stable, reliable person with rapid access to follow-up can be managed differently from someone with evolving symptoms, who lives far from a healthcare facility or cannot stop physical exertion. This organizational dimension does not replace clinical criteria, but it affects the safety of outpatient management and the timeliness with which a transition to dysfunction or arrhythmia can be recognized.

Investigations and Diagnosis

Diagnosis begins by demonstrating a pericarditic syndrome through characteristic pain or an equivalent presentation and objective findings such as a friction rub, ECG changes, new effusion or imaging evidence of pericardial inflammation. The myocardial involvement that defines myopericarditis is documented by elevated biomarkers of myocardial injury in the absence of significant new global or regional dysfunction; CMR and, rarely, biopsy can further characterize the process, and the final formulation should reasonably exclude the principal mimics.

The ECG may show diffuse concave ST elevation, PR depression, subsequent normalization of the segment and T-wave inversion, but the classic sequence is not seen in every patient. Territorial changes, Q waves, wide QRS or blocks require greater caution because they may indicate ischemia or more extensive myocardial involvement; serial tracings and telemetry are more valuable than a single recording for recognizing dynamic changes and arrhythmias.

High-sensitivity troponin documents cardiomyocyte injury, while CRP and ESR describe systemic inflammation and BNP or NT-proBNP signal hemodynamic stress; complete blood count, eosinophils, renal and hepatic function, electrolytes and CK help identify causes, treatment safety and overlap syndromes. Peak troponin alone does not measure severity or prognosis, and a normal value does not exclude focal involvement if sampling is late or clinical probability remains high.

Echocardiography assesses global and regional function, strain, effusion, signs of tamponade, pressures and alternative diagnoses; in classic myopericarditis function is preserved, but subtle strain abnormalities or a small effusion may be present. New hypokinesia or a significant reduction in ejection fraction shifts the diagnosis toward perimyocarditis and changes hospitalization, medications, follow-up and prognosis.

Multiparametric CMR looks for edema with T2 and non-ischemic injury with T1, ECV and LGE, applying the Lake Louise criteria in the appropriate context. Involvement is often inferolateral subepicardial and may be associated with pericardial enhancement or thickening and effusion. A late negative CMR does not exclude an episode already resolving, and a positive study does not identify etiology, but the examination is central to distinguishing myocarditis, infarction and Takotsubo syndrome in patients with non-obstructive coronary arteries.

Coronary assessment with CCTA or angiography depends on age, risk, ECG, pain characteristics and stability. Normal coronary arteries do not conclude the diagnostic pathway because ischemic MINOCA, vasospasm, embolism, dissection and Takotsubo syndrome require specific differentiation; pulmonary embolism, aortic dissection, pneumonia, pleuritis and musculoskeletal pain complete the extracardiac differential.

Endomyocardial biopsy is not routine in stable myopericarditis with preserved function, but becomes indicated if shock, progressive dysfunction, sustained arrhythmias, advanced block, eosinophilia or suspected giant-cell myocarditis, sarcoidosis or checkpoint inhibitor toxicity develops. Etiologic investigation is targeted: blood cultures, tests for tuberculosis, HIV, Borrelia, autoimmunity, PET and extracardiac biopsy are selected on the basis of the phenotype, while indiscriminate viral serology does not demonstrate myocardial infection.

When age, risk factors, pain characteristics or territorial changes make acute coronary syndrome plausible, coronary anatomy is evaluated with invasive or tomographic methods according to urgency. Subsequent CMR more often distinguishes an ischemic subendocardial pattern from an inflammatory subepicardial lesion, but MINOCA, vasospasm and dissection also require dedicated interpretation. Prematurely defining myopericarditis can delay revascularization or antithrombotic therapy, while treating every case as infarction exposes patients to unnecessary drugs.

Serial quantification of troponin and C-reactive protein answers different questions: the former follows myocardial injury, the latter systemic and pericardial inflammatory activity. Discordance between them does not invalidate the diagnosis and may reflect different biological timings, whereas a new increase after a declining phase requires assessment for relapse, premature exertion or an alternative diagnosis. Follow-up echocardiography documents function and effusion without being used as a surrogate for tissue activity.

Treatment and Prognosis

The first measure is relative rest with suspension of intense exercise, accompanied by the initial observation needed to exclude arrhythmias, dysfunction, significant effusion and acute coronary syndrome. In patients with preserved function and a dominant pericarditic component, management largely follows that of pericarditis, using aspirin or an NSAID to control pain and inflammation. Choice, dose and duration are adapted to gastrointestinal risk, renal function, blood pressure and response, with gastroprotection when indicated.

The historical caution regarding high doses of NSAIDs derives from animal models of myocarditis in which some drugs worsened inflammation and outcome, but direct applicability to humans with myopericarditis and preserved function is uncertain. The dose should therefore be sufficient to treat pericarditis without being continued beyond necessity and is gradually reduced after symptom remission and normalization of inflammatory markers. If ventricular dysfunction or heart failure develops, NSAIDs may promote fluid retention and worsen renal function, and the strategy should be reassessed.

Colchicine is established in pericarditis, and recent observational data support a reduction in recurrences also in myopericarditis. It is used in appropriate patients with consideration of body weight, renal and hepatic function, interactions and gastrointestinal toxicity, while the specific evidence remains less extensive than for isolated pericarditis. Corticosteroids are not first-line treatment in uncomplicated idiopathic forms and are reserved for specific indications, contraindications or failure of initial therapies, at the lowest effective dose and with slow tapering.

Etiologic treatment is applied when a treatable cause is demonstrated; antibiotics, antituberculous therapy, treatment of autoimmune disease, withdrawal of the causal drug or immunosuppression for checkpoint inhibitor toxicity, eosinophilic disease and other specific forms follow dedicated protocols. Immunoglobulins and antivirals are not universal empiric therapies, and immunosuppression is not started solely on the basis of troponin elevation and pain.

Monitoring includes symptoms, ECG, troponin, CRP and echocardiography and, in selected profiles, follow-up CMR and Holter monitoring; clinical remission should be accompanied by preserved function, stabilization of biomarkers and absence of significant arrhythmias. Return to sport is more cautious than after isolated pericarditis and is individualized according to myocardial involvement, also using exercise testing and rhythm monitoring.

The prognosis of idiopathic or viral forms with preserved function is generally excellent, and prospective cohorts have shown normalization of function in the great majority of cases. Isolated troponin elevation is not an adverse prognostic marker equivalent to dysfunction. Specific etiologies, extensive or septal LGE, arrhythmias, block, significant effusion and failure to resolve instead define a profile that should not be equated with uncomplicated disease.

Recurrence more often involves the pericardial component and may present with or without new myocardial injury. New pain requires ECG, biomarkers and imaging when appropriate because simple resemblance to the previous episode does not exclude ischemia or a different evolution. Repeated myocardial recurrences should prompt consideration of autoimmunity, drugs, sarcoidosis and genetic cardiomyopathy with hot phases.

The evidence for colchicine in myopericarditis is less extensive than that available for isolated pericarditis, but contemporary observational data support its efficacy and safety in appropriately selected patients. Dose and duration are adapted to body weight, renal and hepatic function, interactions and gastrointestinal tolerance; macrolides, drugs that interfere with CYP3A4 or P-glycoprotein, and severe organ failure increase the risk of toxicity. Prescription does not replace assessment of ventricular function and etiology.

Follow-up does not end when pain disappears because edema, troponin and electrical instability may resolve on different timelines. ECG, echocardiography and biomarkers are reassessed before activity is increased; CMR and rhythm monitoring are particularly useful if LGE persists, palpitations develop or the patient wishes to resume intense sport. A stable scar does not necessarily indicate inflammation requiring treatment, but it modifies risk assessment together with the presence of arrhythmias.

Complications

Pericardial effusion is common but generally modest and does not correlate with the extent of myocardial injury. Rapid accumulation can nevertheless produce tamponade, with hypotension, jugular venous distension, tachycardia, pulsus paradoxus and collapse of the right-sided chambers; in this situation drainage is urgent and fluid analysis is guided by the suspected cause. Progression should be recognized by serial echocardiography, not by pain intensity alone.

The most common late complication is recurrent pericarditis, favored by incomplete response, excessively rapid corticosteroid tapering and autoinflammatory causes. Each recurrence may prolong functional limitation and treatment but does not necessarily imply new myocardial injury; troponin measurement and selective CMR distinguish pericardial reactivation from recurrent myopericarditis.

Premature beats and supraventricular tachycardias may accompany the active phase, whereas sustained ventricular tachycardia or ventricular fibrillation are rare in uncomplicated disease and require risk reclassification. Edema and inflammation generate transient instability, while persistent LGE may leave an arrhythmogenic scar; normalization of ejection fraction does not automatically eliminate this substrate.

Progression to ventricular dysfunction identifies perimyocarditis or more extensive myocarditis and may lead to heart failure, functional mitral regurgitation and remodeling. This transition is uncommon in initially uncomplicated forms but should be sought when dyspnea, natriuretic peptide levels, arrhythmias or echocardiographic abnormalities increase; timely introduction of heart failure therapy depends on the phenotype and is not delayed pending complete etiologic definition.

Constrictive pericarditis is rare after idiopathic or viral forms but assumes greater importance in tuberculosis, purulent infections, after radiation or surgery, and in persistent recurrences. Findings include right-sided congestion, respiratory variation in flows and ventricular interdependence and require multimodality imaging; transient inflammatory constriction may regress with therapy, whereas established fibrotic constriction may require pericardiectomy.

Treatment complications include renal injury, bleeding and gastrointestinal toxicity from NSAIDs, diarrhea and drug interactions from colchicine, and infections, osteoporosis and corticosteroid dependence. Prevention requires appropriate dosing, review of interactions and organ monitoring, avoiding prolonged treatment based solely on a stable CMR finding not accompanied by activity.

The main diagnostic complication is attributing chest pain with troponin elevation to myopericarditis without having excluded an occlusion, dissection, embolism or another cause of MINOCA. The opposite error is treating as simple pericarditis a patient with new dysfunction or electrical instability; the distinction between pericardial phenotype and myocardial phenotype must be reassessed throughout the entire course.

Constrictive pericarditis is rare after an uncomplicated idiopathic or presumably viral form and should prompt reconsideration of tuberculosis, bacterial infection, neoplasia, radiation or immune disease when right-sided congestion and signs of ventricular interdependence appear. Echocardiography, CT and CMR distinguish transient inflammatory constriction from established pericardial fibrosis; the distinction is clinically relevant because the former may regress with medical therapy, whereas the latter may require surgical assessment.