Acute myocarditis

Article written and reviewed by Dr Luca Moretti

Acute myocarditis corresponds to the recent and biologically active phase of an inflammatory disease of the myocardium, recognizable through the onset of symptoms or objective findings of cardiomyocyte injury, edema, mechanical dysfunction or electrical instability. The adjective “acute” places the process in relation to onset but does not define its severity: a painful presentation with preserved function and a form progressing to shock both belong to the acute phase, despite radically different prognoses and care needs. Even the date of symptoms does not necessarily coincide with biological onset, because a subclinical period may precede pain and heart failure and a hot phase may represent the first evident expression of a pre-existing genetic substrate.

Initial assessment is guided by three main phenotypes: the infarct-like phenotype, with chest pain, ST-T changes and troponin elevation; the heart-failure phenotype, with dyspnea, congestion or low output; and the electrical phenotype, in which palpitations, syncope, ventricular tachycardia or conduction disorders predominate. These presentations often overlap and severity is determined by the clinically most dangerous component, not by the number of findings. Fulminant myocarditis specifically identifies the subgroup with hemodynamic instability requiring inotropes or circulatory support and therefore should not be used as a synonym for extensive CMR abnormalities in a patient who remains stable.

The acute phase gives CMR its greatest sensitivity for edema and non-ischemic injury, but this diagnostic window narrows when the examination is delayed and tissue water regresses, while LGE may persist and progressively acquire the meaning of scar. The pathway should therefore be rapid without becoming precipitous: alternative emergencies are excluded as a priority, but tissue characterization is not postponed until biological information is lost, nor, in high-risk phenotypes, is the opportunity to perform biopsy delayed when it can still modify treatment.

Incidence remains underestimated and is affected both by access to high-sensitivity troponin and CMR and by the criteria used to include cases. In Western registries the infarct-like presentation occurs especially in young men, but the disease affects both sexes and every age group, with young children and older adults more often observed for heart failure or systemic manifestations. Prognosis cannot be inferred from this demographic distribution: in a contemporary Italian cohort, uncomplicated presentations showed no late major events, whereas five-year risk was concentrated among patients who at onset had an ejection fraction below 50%, ventricular arrhythmias or low-output syndrome.

Acute prognosis results from the interaction among hemodynamic stability, electrical stability, function of both ventricles and etiology, not from the isolated magnitude of a biomarker. Very high troponin in the absence of dysfunction does not necessarily imply a worse outcome, whereas a modest increase loses any reassuring value when block, arrhythmias or shock coexist. Stratification must therefore be phenotypic and serial, because during the first hours the transition from an apparently circumscribed presentation to hemodynamically or electrically unstable disease may be rapid.

Etiology, Pathogenesis and Pathophysiology

The etiologic spectrum includes infections, post-infectious immune responses, autoimmunity, drugs, hypersensitivity reactions, checkpoint inhibitors, eosinophilic syndromes, sarcoidosis and other granulomatous diseases; an acute phase may also represent the first manifestation of a genetic cardiomyopathy, particularly one associated with DSP variants. Because in practice a cause often remains unproven, it is not correct to fill the uncertainty with the generic label “viral”: a respiratory prodrome increases the plausibility of a trigger but demonstrates neither the presence of the agent in the heart nor the mechanism responsible for injury.

In cardiotropic infections, the initial phase combines replication and direct cytotoxicity with activation of innate immune sensors. Interferons tend to limit spread, while cytokines, complement and effector cells increase permeability, edema and cardiomyocyte injury, leading in some cases to elimination of the agent and in others to low-level persistence in specific compartments. In subsequent days, activation of T and B lymphocytes broadens the response: cytotoxic clones eliminate cells displaying antigens but, through mimicry, may recognize cardiac epitopes, while autoantibodies and T helper lymphocytes prolong inflammation beyond the trigger. Final intensity depends on the interaction among antigenic burden, host immunogenetics, sex, hormonal milieu and regulatory capacity, explaining why similar exposures produce different phenotypes.

Interstitial and intracellular edema increases the water content detectable with T2 sequences, while vasodilation, hyperemia and expansion of the extracellular space increase native T1 and ECV; when necrosis and membrane disruption allow gadolinium accumulation, LGE appears. These signals are not synonymous but represent different and temporally mobile components of acute injury. Function may decline because of actual cardiomyocyte loss or because of reversible depression mediated by cytokines and altered calcium handling; consequently, a thickened and hypokinetic ventricle may reflect edema rather than true hypertrophy, as suggested by rapid normalization of wall thickness during recovery. Diffuse involvement favors low output, whereas focal lesions may leave ejection fraction apparently preserved.

Electrically, inflammation alters connexins, ion channels and cell-to-cell coupling, while edema and necrosis produce conduction slowing, dispersion of refractoriness and reentry circuits; catecholamines and unstable electrolytes further lower the arrhythmic threshold. This explains the possibility of malignant arrhythmias even with preserved systolic function. The conduction system is particularly vulnerable when lesions involve the septum and, although sarcoidosis, giant-cell myocarditis, Lyme disease and checkpoint inhibitor-associated myocarditis show a particular propensity for block, no electrical pattern is pathognomonic. Advanced block in a young adult without a drug-related or degenerative explanation should therefore increase the urgency of tissue characterization.

In the infarct-like presentation, injury often has an inferolateral subepicardial distribution and produces pain and troponin elevation in the absence of coronary occlusion. Vasospasm, microvascular dysfunction and microthrombosis may coexist, but their presence does not justify automatically attributing them to the same inflammatory mechanism. The non-ischemic LGE pattern helps distinguish myocarditis from infarction, particularly when CMR is performed early enough to document edema and transient injury before they subside.

During resolution, removal of necrotic cells is accompanied by matrix deposition: if injury is limited, restitutio ad integrum may occur, whereas more extensive injury leaves a subepicardial or intramural scar capable of continuing to affect conduction. Transition toward chronic myocarditis occurs when immune activity, symptoms or dysfunction do not resolve with this phase and neurohormonal and fibrotic remodeling acquires a self-sustaining dynamic.

Exercise performed during infection or the active phase increases heart rate, wall stress and adrenergic signaling, and in experimental models intense activity is associated with greater replication and mortality. This evidence supports temporary restriction of exertion but does not justify prolonged and indiscriminate inactivity: return is guided by demonstration of clinical, biochemical, functional and electrical remission, not by the mere passage of a predefined interval.

Clinical Manifestations

The interview should reconstruct the temporal sequence, recording the onset of fever or systemic symptoms, any symptom-free interval, onset of pain, evolution of dyspnea, syncopal episodes and their relationship to exertion. A careful history helps distinguish pericarditic, ischemic, pleuritic and musculoskeletal components without assigning absolute value to a single feature. In the infarct-like phenotype, retrosternal pain may be severe, radiating and accompanied by nausea or sweating, while ECG and troponin may sometimes be indistinguishable from those of myocardial infarction; the priority therefore remains exclusion of a coronary occlusion or dissection. Young age lowers the probability of atherosclerosis but does not eliminate coronary anomalies, embolism, vasospasm or other time-dependent causes.

When the pericarditic component predominates, pain tends to worsen with inspiration and recumbency and improve when sitting up, sometimes in association with low-grade fever and a friction rub; troponin elevation documents myocardial involvement, while the presence or absence of dysfunction contributes to distinguishing perimyocarditis from myopericarditis. A modest effusion is common and by itself does not measure severity. In the heart-failure phenotype, by contrast, reduced exercise tolerance, dyspnea, orthopnea and asthenia may progress to dyspnea at rest, oliguria, confusion and cold extremities, signaling low output that requires intensive treatment; pain may be absent, especially in diffuse forms and young children.

In the arrhythmic phenotype, palpitations, syncope and cardiac arrest may precede any sign of pump failure; in particular, sudden syncope without prodromes, an arrhythmia during exertion or sustained ventricular tachycardia are warning signs requiring telemetry and urgent characterization, while bradycardia or episodic intolerance may reflect intermittent block. Etiologic history taking should therefore proceed in parallel, looking for infections, drugs introduced in the preceding weeks, immunotherapy, bites, travel, high-risk foods, occupational exposures, autoimmune diseases and extracardiac manifestations. Eosinophilia, rash and fever after a drug suggest hypersensitivity; muscle weakness during checkpoint inhibitor therapy suggests an immune overlap; and previous episodes together with family history increase the probability of genetic predisposition.

On arrival, assessment of airway, breathing and circulation precedes nosologic definition because tachypnea, hypoxemia, hypotension, altered mental status, prolonged capillary refill and oliguria determine the care setting; even preserved blood pressure, if accompanied by rising lactate, may conceal compensated shock. Cardiovascular examination looks for jugular venous distension, a third heart sound, gallop rhythm, functional murmurs and a friction rub, integrating crackles as a sign of edema, hepatomegaly and edema as expressions of right-sided congestion, and an irregular or slow pulse as evidence of arrhythmia or block. The absence of auscultatory findings, however, does not exclude an infarct-like presentation with preserved function.

In children, the presentation may mimic bronchiolitis, sepsis or gastroenteritis, but persistent tachycardia, hepatomegaly, delayed capillary refill and cardiomegaly should raise consideration of a cardiac cause; in adolescents, pain and troponin elevation become more common, while age-specific thresholds and support strategies remain necessary. During hospitalization, the course of pain, ST-T changes, troponin, arrhythmias, urine output and function is observed as a trajectory because initial improvement may be followed by deterioration, and new ectopy, QRS widening or an increasing need for vasopressors may precede overt shock. Surveillance must therefore be proportionate to the risk of clinical progression, not merely to the patient's appearance at triage.

Investigations and Diagnosis

The first goal of testing is to recognize instability and time-dependent diagnoses, integrating an ECG obtained within minutes, serial troponin, bedside echocardiography and coronary assessment with blood gas analysis, lactate, organ function and electrolytes. Chest radiography may show congestion or cardiomegaly but remain normal in focal forms. ECG may show diffuse concave ST elevation, regional changes, PR depression, T-wave inversion, Q waves, low voltages, blocks and QRS widening, without any configuration alone confirming the diagnosis or a normal tracing excluding it. Wide QRS, advanced block or ventricular arrhythmias instead carry prognostic value and strengthen the indication for intensive monitoring.

Troponin should be interpreted as a marker of injury rather than etiology: serial values describe its dynamics, but peak height does not linearly measure either inflamed mass or prognosis. CRP, natriuretic peptide, creatinine, transaminases, CK and complete blood count complete the systemic phenotype and may reveal eosinophilia, overlap with myositis or organ injury. Echocardiography measures ejection fraction, strain, right ventricular function, pressures and effusion, documenting any transient thickening, global or segmental hypokinesia, reduced strain and mitral regurgitation; normal function nevertheless does not exclude focal inflammation. In unstable patients, repeated examination recognizes deterioration or recovery more rapidly than CMR can.

CCTA and coronary angiography are selected according to the probability and urgency of coronary disease; if no culprit lesion emerges, early CMR allows myocarditis, Takotsubo syndrome and non-obstructive infarction to be distinguished in many patients with MINOCA, making a normal angiogram a step rather than the end point of diagnosis. The protocol includes cine imaging, T2, T1 and T2 mapping, ECV and LGE: edema and elevated T1 without LGE may represent reversible injury, while subepicardial or intramural LGE documents a non-ischemic distribution and dysfunction or effusion adds supportive elements. Performance during the symptomatic phase increases the probability of capturing activity before it regresses.

According to the updated Lake Louise criteria, the combined presence of at least one T2-based marker and at least one T1-based marker supports acute myocardial inflammation with greater specificity; an incomplete result, however, does not negate the diagnosis when clinical probability and other evidence remain strong. CMR does not reliably distinguish lymphocytic myocarditis from eosinophilic, giant-cell or infectious forms and, when the question concerns a subtype capable of changing therapy, it does not replace biopsy.

In the absence of a single self-sufficient clinical criterion, the 2025 ESC guidelines require a compatible syndrome accompanied by objective documentation through ECG, biomarkers, imaging or histology and reasonable exclusion of the principal mimics; certainty increases with concordance across domains, whereas a merely possible diagnosis should not become certainty in the report. Biopsy becomes urgent in the presence of shock, sustained ventricular arrhythmias, advanced block, rapid progression, significant eosinophilia or suspected cause requiring immunosuppression. Tissue should be collected in multiple samples and preserved in appropriate media for histology, immunohistochemistry and PCR, using electroanatomic or imaging guidance in focal processes to reduce sampling error.

Etiologic tests are guided by history, requesting blood cultures in the presence of fever or sepsis, Borrelia testing when exposure and block are consistent, Trypanosoma testing in people from endemic areas, HIV and other infection testing according to risk, and autoimmune testing in the presence of systemic signs. Viral serology does not identify the agent in the myocardium and does not constitute causal evidence, while PET, chest CT and extracardiac biopsy may selectively complete the evaluation for suspected granulomatous disease.

Final stratification separates uncomplicated from complicated disease by integrating left or right ventricular dysfunction, low output, sustained arrhythmias, advanced block, syncope, and the extent and location of LGE. It is this combination, reassessed over time, that determines hospitalization, monitoring intensity and follow-up; in complicated, recurrent or familial presentations, genetic evaluation adds an indispensable level to risk definition.

Treatment and Prognosis

Immediate treatment is modulated by stability: low-risk forms may be observed while investigations are completed rapidly, whereas dysfunction, arrhythmias, syncope, block or a potentially aggressive etiology require hospitalization; shock and refractory arrhythmias require transfer to a center capable of urgent biopsy, mechanical support and transplantation. Relative rest reduces metabolic demand and adrenergic stimulation, so intense activity and competitive sport are suspended during the active phase, while unnecessary immobility is avoided and thromboembolic prophylaxis is applied to at-risk inpatients. Alcohol, cocaine, stimulants and cardiotoxic drugs should be eliminated as potential amplifiers of injury.

Congestion is controlled with diuretics and, when blood pressure permits, vasodilators; in hemodynamically stable patients with reduced ejection fraction, heart failure therapy is introduced, postponing beta-blockers until shock and severe congestion have resolved. Titration continues after discharge because remodeling proceeds during recovery. If pericarditic pain and preserved function dominate the presentation, NSAIDs and colchicine may be used with gastric protection and renal assessment, whereas in symptomatic heart failure NSAIDs are avoided because of the risk of fluid retention and renal worsening. In every case, analgesia does not replace surveillance of troponin, rhythm and function.

Unstable arrhythmias require immediate electrical treatment and symptomatic block may require temporary pacing; amiodarone is often preferred when structural dysfunction is present, but every antiarrhythmic must be adapted to QT, organ function and interactions, while a wearable defibrillator may protect selected patients during uncertainty about recovery. Immunosuppression, by contrast, is not started indiscriminately: it must be timely in giant-cell myocarditis, eosinophilic necrotizing myocarditis, active sarcoidosis, checkpoint inhibitor toxicity and some autoimmune forms, whereas in stable lymphocytic myocarditis it requires tissue and etiologic selection. When instability is life- threatening and suspicion of an aggressive histotype is high, biopsy and treatment must be coordinated without avoidable delays.

Antimicrobials are prescribed when a treatable agent is identified or strongly suspected, following specific protocols for antibiotics in Lyme disease and diphtheria, antiparasitic treatment in the appropriate phase of Chagas disease and antifungals in immunosuppressed patients; empiric antiviral therapy, by contrast, is not standard for most acute presentations. In uncomplicated disease, symptoms, ECG and biomarkers are monitored and an early echocardiogram is scheduled. For symptomatic patients, the ACC consensus proposes reassessment after two to four weeks and a new follow-up around six months, including CMR in higher-risk profiles and bringing the timing forward if pain, dyspnea, syncope or palpitations recur.

Return to exertion presupposes clinical remission, absence of evolving injury, functional recovery and no significant arrhythmias on Holter monitoring and exercise testing; three to six months is a frequent reference for symptomatic forms, but the decision remains individualized and risk-guided, particularly when LGE persists without edema. Prognosis is generally favorable with preserved function, absence of arrhythmias or low output and rapid improvement, whereas stage D, biventricular dysfunction, sustained arrhythmias, block, anteroseptal or extensive LGE and failure to resolve define an adverse profile. The six-month trajectory is therefore more informative than the initial peak troponin alone.

Complications

Edema and contractile depression may produce acute heart failure with elevated filling pressures: pulmonary congestion causes hypoxemia and increased work of breathing, while right-sided involvement causes hepatic congestion and worsens renal perfusion. Although part of the dysfunction is reversible, the initial phase requires close monitoring because progression to shock combines reduced output, hypotension or compensatory vasoconstriction and organ injury. Acidosis and catecholamines in turn increase arrhythmias and oxygen consumption, establishing a vicious cycle in which delayed support favors multiorgan failure and reduces the probability of recovery.

Ventricular arrhythmias may appear without warning because edema generates dynamic instability, while necrosis and LGE create a persistent substrate on which ventricular tachycardia and fibrillation may cause arrest and sudden death; this risk does not disappear with normalization of ejection fraction alone. Atrioventricular block may also be transient or permanent and, if it progresses rapidly, requires pacing together with investigation for high-priority etiologies such as Lyme disease, sarcoidosis, giant-cell myocarditis or immune toxicity. Unless a persistent need exists, the choice of a permanent device is reassessed after the edematous phase regresses.

A pericardial effusion may accompany myocarditis and, although it rarely progresses to tamponade, becomes dangerous when it increases rapidly; echocardiography distinguishes an incidental finding from hemodynamic compromise, while recurrent pericarditis may prolong pain beyond resolution of myocardial injury. Akinesia and severely reduced function also favor ventricular thrombus formation and the consequent risk of cerebral or systemic embolism. If the apex is poorly visualized, echocardiographic contrast and CMR increase sensitivity, but anticoagulation follows demonstration of the thrombus or another clinical indication, not the diagnosis of myocarditis itself.

After edema disappears, a scar may remain, and persistent LGE without signs of activity, particularly when septal, is associated with a less favorable prognosis and justifies longer arrhythmic monitoring; even its quantitative reduction does not necessarily equal complete disappearance of fibrosis. In some patients ejection fraction remains reduced and dilatation progresses toward inflammatory cardiomyopathy, with remodeling, functional mitral regurgitation and neurohormonal activation capable of progressing when the acute phase appears over. Continuation of heart failure therapy and follow-up serve precisely to recognize this transition.

Relapse may follow a new infection, drug re-exposure, autoimmune reactivation or a genetic hot phase, and multiple episodes add necrosis and fibrosis, modifying indications for biopsy and genetic testing. New pain should not, however, automatically be attributed to the previous diagnosis without reassessing the coronary arteries and the differential diagnosis. Iatrogenic consequences are added to those of the disease, including renal injury from contrast or drugs, bleeding from biopsy or anticoagulation, infections from immunosuppression and complications of mechanical support; preventing them requires appropriateness of testing, multidisciplinary coordination and an explicit link between each procedure and the clinical decision it is intended to modify.

One of the most important consequences of an unrecognized acute phase is loss of the diagnostic window because, over time, edema and infiltrate may disappear leaving only scar and making it much more difficult to distinguish etiology, residual activity and irreversible substrate. Timely assessment therefore serves not only to assign a name, but also to prevent shock, treat specific subtypes while they are still modifiable, and build follow-up proportionate to the actual risk.