Myocarditis

Meet the patient

A 24-year-old man walks into the emergency department at 3am with pleuritic central chest pain, palpitations, and a flu-like illness a week ago. The ECG shows widespread ST elevation with PR depression; his high-sensitivity troponin is 900 nanogram per litre; his coronary angiogram is clean. The cath lab stands down. Now the real question begins.[1]

Two exam questions now sit on the end of the bed, and they are the two that decide every myocarditis stem: what is this, and how sick will he get? The first is answered by cardiac MRI and the Lake Louise Criteria; the second — fulminant versus not, lymphocytic versus giant cell — decides whether he goes to the ward, to ICU on VA-ECMO, or to the biopsy suite.[3][4]

Troponin up, coronaries clean — the triage fork that frames everything

This is the opening discriminator, and almost every myocarditis stem is built on it. A young patient with chest pain, a raised troponin and ST changes whose coronary angiogram is normal is a patient whose myocardium is inflamed, not infarcted — and the next move is cardiac MRI, not a second troponin and discharge to sport.[2][3]

The formal ESC definition is built around exactly this fork. Myocarditis is an inflammatory disease of the myocardium confirmed by histological (Dallas), immunological and immunohistochemical criteria, and the modern definition layers on a compatible clinical picture — symptoms, raised troponin, ECG, echo and MRI abnormalities — with either biopsy-proven inflammation or characteristic Lake Louise features on CMR.[1][2]

When that same inflammation produces ventricular dysfunction the label widens to inflammatory cardiomyopathy — the two sit on a continuum linked by the WHO and ISFC cardiomyopathy classification. The bedside skill is not reciting the textbook triad (which arrives complete in a minority) but recognising the three overlapping phenotypes — ACS-mimic, new heart failure, and arrhythmia or sudden death — excluding obstructive coronary disease, then risk-stratifying for the fulminant and giant-cell end of the spectrum.[3][4]

Etymology for viva gold: myocarditis is Greek — mys, myos (muscle) plus kardia (heart) plus itis (inflammation). The Dallas criteria, still the histological language, take their name from the 1987 Dallas consensus conference that wrote them; the Lake Louise criteria take theirs from the Alberta hotel that hosted the 2009 consensus — two cities, two standards.[2][6]

Four axes, one disease — the classification that changes what you do

Four classification axes run in parallel, and each one changes a different decision. Aetiology decides whether the cause is treatable (stop clozapine; give steroids for giant cell). Histology decides whether immunosuppression helps. Course — fulminant versus acute — decides the level of care and, paradoxically, the prognosis. Phenotype decides the work-up.[2][4]

By aetiology (the axis that drives therapy):[3]

• Viral — commonest in the developed world. Coxsackievirus B3 is the classical exam answer; parvovirus B19 is now the commonest PCR-positive virus in adult biopsies, then enteroviruses, adenovirus, HHV-6, EBV, CMV, influenza, SARS-CoV-2, HIV, hepatitis C.
• Bacterial — Corynebacterium diphtheriae (toxin-mediated), Borrelia burgdorferi (Lyme, with AV block), Mycoplasma, streptococcus, staphylococcus.
• Protozoal and parasitic — Trypanosoma cruzi (Chagas, the commonest cause of myocarditis-related cardiomyopathy in Latin America), Toxoplasma gondii in the immunocompromised, Trichinella.
• Fungal — Aspergillus, Candida, in immunocompromised hosts.
• Immune-mediated — systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, sarcoidosis, idiopathic giant cell myocarditis.
• Hypersensitivity and drug-induced (eosinophilic) — clozapine, penicillins, sulfonamides, cephalosporins, thiazides, furosemide, dobutamine, methyldopa, phenytoin, carbamazepine, smallpox vaccine.
• Toxic — anthracyclines (doxorubicin, daunorubicin), cocaine, alcohol, radiation, trastuzumab, cyclophosphamide, 5-fluorouracil, carbon monoxide, lead, venom.
• Vaccine-associated — smallpox vaccine historically; mRNA COVID-19 vaccines, notably in young males after the second dose.[1]

By histology — the Dallas classification (Aretz 1987), still the biopsy language:[2]

• Active myocarditis — inflammatory infiltrate with myocyte necrosis or degeneration not attributable to ischaemia.
• Borderline myocarditis — inflammatory infiltrate without myocyte damage.
• No myocarditis.[1]

By cellular infiltrate: lymphocytic (commonest, viral), eosinophilic (hypersensitivity, parasitic, Churg-Strauss), giant-cell (idiopathic, aggressive autoimmune), granulomatous (sarcoid), neutrophilic (early bacterial, sepsis). The infiltrate is the single histological fact that decides whether immunosuppression is on the table.[1]

By clinical course (McCarthy, Mayo, 2000) — the axis that produces the fulminant paradox:[7]

[7]

By clinical phenotype (practical, drives work-up): ACS-mimic; new-onset heart failure or cardiomyopathy; arrhythmia or sudden cardiac death; incidental subclinical troponin rise.[3]

How common, and who gets it

True incidence is unknown because most cases are subclinical and self-limiting — but myocarditis is the silent killer behind a striking share of sudden death in the young. Autopsy series put it at roughly 5 to 10 percent of sudden cardiac deaths in young adults, rising to up to 20 percent in athletes under 35.[3]

The host profile that should raise the question:[2][3]

• Young adults under 40 — peak incidence 20 to 40 years; male predominance, about 2 to 1 (oestrogen is cardioprotective in mouse models).
• Athletes — disproportionate sudden-death risk; exertion during viraemia worsens injury.
• Pregnancy and peripartum — overlaps with peripartum cardiomyopathy.
• Immunocompromised — HIV, transplant, chemotherapy; atypical organisms (Toxoplasma, CMV, fungal).
• Genetic predisposition — HLA-DR haplotypes; rare familial giant cell myocarditis.
• Endemic exposures and recent triggers — Chagas in Latin America; tick bites (Lyme); a recent viral illness, vaccine dose, or new drug (clozapine, sulfonamide, anthracycline).[1]

[1]

Three phases of viral injury — entry, immune, remodelling

The human disease mirrors the classical three-phase coxsackievirus B3 mouse model, and the phases are the cluster rule for viva. Phase 1 is the virus, phase 2 is you, phase 3 is the scar. Knowing which phase dominates decides why immunosuppression can help or harm.[3]

Phase 1 — acute injury, the first week. The virus binds the coxsackievirus and adenovirus receptor (CAR) on the intercalated disc — a tight-junction protein coxsackie B and adenoviruses share — with decay accelerating factor (DAF, CD55) as co-receptor. Once inside, viral proteases 2A and 3C cleave dystrophin, rupturing the dystrophin-glycoprotein complex and the sarcolemma, allowing calcium influx and myocyte necrosis with troponin leak.[3]

Phase 2 — immune-mediated injury, days 7 to 14. Dying myocytes release damage-associated molecular patterns — cardiac myosin, heat-shock proteins, ATP — sensed by TLR3, TLR4 and the NLRP3 inflammasome. Innate immunity (NK cells, M1 macrophages, type I interferons) is followed by CD8+ cytotoxic T cells killing infected cells via MHC class I, CD4+ Th1 and Th17 cells recruiting more inflammation, and B cells producing anti-cardiac myosin autoantibodies through molecular mimicry. By week two the immune phase — not the virus — dominates pathology, which is exactly why blanket immunosuppression can be harmful in straightforward lymphocytic disease yet life-saving in giant cell.[3]

Phase 3 — chronic remodelling, weeks to months. A subset progress through viral persistence (PCR-positive biopsy) and ongoing autoimmunity to adverse remodelling and dilated cardiomyopathy with fibrosis. Predictors include certain viruses (adenovirus can be worse than PVB19), HLA-DR4, sustained LV dysfunction, and recurrent inflammation.[2]

Why the ECG and troponin mimic MI: patchy myocyte necrosis with adjacent pericardial inflammation produces regional ST elevation, T-wave inversion, PR depression (perimyocarditis) and a troponin leak indistinguishable from plaque rupture — which is precisely why coronary angiography is mandatory when the picture (young, prodrome, atypical pain) does not fit obstructive CAD.[3]

The chameleon at the bedside — four phenotypes

Myocarditis is a chameleon, and the classical triad — chest pain, heart failure, arrhythmia — arrives complete in only a minority. The four clinical phenotypes are the examinable patterns; recognise the one in front of you and the work-up follows.[2][3]

Phenotype 1 — the ACS-mimic (commonest in young adults). Pleuritic or atypical chest pain, often preceded by a viral prodrome — fever, myalgia, sore throat, diarrhoea — one to two weeks earlier. ECG shows ST elevation, T-wave inversion or non-specific ST-T changes; troponin is markedly raised. Diffuse ST elevation with PR depression points to perimyocarditis.[3]

Phenotype 2 — new heart failure or cardiomyopathy. Dyspnoea, orthopnoea, fatigue, fluid retention, sometimes rapidly progressive. Echo shows LV dysfunction, often global, sometimes regional. Fulminant myocarditis is the severe end of this spectrum — cardiogenic shock within days of a viral illness, hypotension, pulmonary oedema, multisystem hypoperfusion.[7]

Phenotype 3 — arrhythmia or sudden cardiac death. Palpitations, syncope, ventricular tachycardia or fibrillation, atrioventricular block (high-grade block shouts giant cell, sarcoid, Lyme, diphtheria), or sudden death — especially in athletes. An unexplained troponin rise after a resuscitated arrest is the clue.[3]

Phenotype 4 — subclinical or incidental. Troponin rise in systemic viral illness (influenza, COVID-19) without cardiac symptoms; increasingly recognised with widespread troponin testing.[1]

At the bedside look for: fever, tachycardia often out of proportion to fever, S3 gallop, bibasal crackles, raised JVP, pericardial friction rub (perimyocarditis), functional mitral or tricuspid regurgitation murmurs, and signs of low output — cool peripheries, oliguria, confusion — in fulminant disease. A systemically well patient with normal haemodynamics, a normal echo and a small troponin rise most likely has mild myocarditis and a good prognosis.[2]

The atypical presentations examiners love:[4]

• Elderly — heart failure dominates, not chest pain; prodrome may be absent; easily mistaken for ischaemic cardiomyopathy.
• Diabetic — pain muted; presents silently as new HF or arrhythmia.
• Pregnant or peripartum — overlaps with peripartum cardiomyopathy; high index of suspicion.
• Immunocompromised — atypical organisms (CMV, Toxoplasma, fungal); can present fulminant with little prodrome.
• Athlete — may present only as syncope or sudden death during exertion.[1]

What it is not — the mimic face-off

Myocarditis is a diagnosis of pattern plus exclusion of mimics, and the table below is the chest-pain SAQ cornerstone. The single highest-yield differential question is myocarditis versus ACS in a young patient: normal coronaries plus the syndrome jumps myocarditis (or Takotsubo) to the top of the list, and the next test is cardiac MRI.[3][4]

[3]

One-line discriminator: normal coronaries plus troponin plus ST changes, in a young patient with a prodrome — reach for the MRI, not the discharge summary. Subendocardial, coronary-territory LGE is ischaemia; subepicardial or mid-wall inferolateral LGE is myocarditis.[3]

The bedside round — severity decides the bed

There is no bedside sign pathognomonic of myocarditis, so the examination has two jobs: exclude alternatives and grade severity. Vital signs drive triage — temperature (fever favours myocarditis or pericarditis over ACS), heart rate, respiratory rate, oxygen saturation, blood pressure, lactate (a rising lactate signals poor perfusion or cardiogenic shock), urine output, conscious level.[3][4]

Run the cardiovascular examination in order: S3 gallop for LV dysfunction, bibasal crackles, raised JVP, pericardial friction rub best heard at the left sternal border leaning forward in full expiration (perimyocarditis), functional mitral regurgitation from LV dilatation, and the cool peripheries, weak pulse and mottled skin of low output. Then hunt for extra-cardiac clues: rash and lymphadenopathy (viral, sarcoid), arthritis (SLE, rheumatoid), uveitis or hilar fullness (sarcoid), erythema chronicum migrans (Lyme), a recent vaccination site.[1]

Severity red flags that warrant ICU and biopsy — memorise this cluster, because together they raise giant cell myocarditis, which is biopsy-defined and treatable: sustained ventricular arrhythmia, high-grade or complete AV block, haemodynamic instability or cardiogenic shock, rapidly progressive heart failure, and multisystem organ dysfunction.[4]

Investigations — syndromic, after the coronaries are clean

No single test diagnoses myocarditis; the diagnosis is syndromic. Compatible clinical picture, plus raised troponin, plus ECG and echo abnormalities, plus characteristic CMR, with or without biopsy — all after exclusion of coronary artery disease.[2][9]

First-line bloods:[3]

• High-sensitivity troponin — the hallmark; typically markedly and persistently raised, often higher than in ACS or with a different kinetic profile (sustained elevation rather than rise-and-fall). A normal troponin does not exclude myocarditis but makes florid disease unlikely.
• BNP or NT-proBNP — raised with myocardial strain or heart failure; prognostic.
• ESR and CRP — non-specific; raised in active disease, normal in the chronic phase.
• Full blood count — eosinophilia (Churg-Strauss, hypersensitivity), lymphopenia (viral, HIV), atypical lymphocytes (EBV).
• U&E, LFTs, TFTs — renal and liver function (multisystem involvement in fulminant disease); exclude thyroid storm.
• CK and CK-MB — can be elevated, especially with concurrent myositis.
• Blood cultures if bacteraemia or sepsis; lactate for perfusion.[1]

Viral serology and PCR — selected, not routine:[2]

• SARS-CoV-2 PCR or antigen; influenza and RSV PCR in respiratory season.
• Enterovirus and coxsackievirus, parvovirus B19, adenovirus, HHV-6, EBV, CMV PCR (blood and/or nasopharyngeal) when clinically indicated.
• HIV serology; Borrelia antibodies with tick exposure; Trypanosoma cruzi serology with travel or exposure risk.
• Autoimmune screen (ANA, anti-dsDNA, ANCA, rheumatoid factor) when immune-mediated disease is suspected.[1]

The 12-lead ECG is abnormal in most symptomatic patients but non-specific:[2]

• Sinus tachycardia (commonest), non-specific ST-T changes, T-wave inversion.
• ST elevation — regional (mimics MI) or diffuse concave with PR depression (perimyocarditis).
• Pathological Q waves, low voltages, AV block — any degree; high-grade or complete heart block shouts giant cell, sarcoid, Lyme, diphtheria.
• Atrial and ventricular arrhythmias — atrial fibrillation, ventricular tachycardia, ventricular fibrillation, sudden death.[1]

Chest X-ray is usually normal early; later it may show cardiomegaly, pulmonary venous congestion, pulmonary oedema or a pleural effusion. Look specifically for hilar lymphadenopathy — sarcoid.[1]

Echocardiography is first-line imaging, and a normal echo does not exclude myocarditis. Look for LV systolic dysfunction (global favours myocarditis or DCM; regional favours ACS but occurs in both), increased wall thickness and brightness from oedema, wall-motion abnormalities, pericardial effusion (perimyocarditis), and intracardiac thrombus. The fulminant pattern is the one to recognise: severe global dysfunction with a thick-walled, non-dilated ventricle — McCarthy's distinguishing feature, against the dilated thin-walled ventricle of acute non-fulminant disease.[3][7]

Coronary angiography is mandatory in any ACS-mimic to exclude obstructive epicardial disease. Normal coronaries plus the syndrome is the fork that lifts myocarditis (or Takotsubo) to the top of the differential and sends you to cardiac MRI.[2]

Cardiac MRI — the Lake Louise number rule

Cardiac MRI is the non-invasive diagnostic standard, and the Lake Louise Criteria are the number rule every candidate must reproduce. Two versions, one decision: the original 2009 asked for 2 of 3; the 2018 update asks for at least one T2-based AND one T1-based criterion.[5][6]

Lake Louise — original (Friedrich 2009). With a compatible clinical picture, the diagnosis is supported if 2 or more of 3 are present:[6]

1. Regional LV wall-motion abnormality (hypo-, a- or dyskinesia), with or without global LV dysfunction.
2. Myocardial oedema — T2-weighted ratio of myocardium to skeletal muscle at least 1.8, OR absolute T2 relaxation time at least 59 ms.
3. Late gadolinium enhancement in a non-ischaemic pattern: mid-wall, subepicardial, or patchy; typically inferolateral or anteroseptal; sparing the subendocardium.[1]

Lake Louise — updated (Ferreira 2018). Adds parametric mapping; diagnosis supported if at least one T2-based AND one T1-based criterion is positive:[5]

• T2-based (oedema): regional or global T2 signal increase — T2 mapping at least 2 standard deviations above normal, or T2 ratio at least 1.8.
• T1-based (injury, fibrosis, increased extracellular volume): native T1 mapping increased (at least 2 SD above normal), or extracellular volume fraction increased, or non-ischaemic LGE present.
• Mapping is now preferred over the T2 ratio because it is more reproducible across centres.[1]

[1]

The LGE discriminator — one line, worth a mark: subepicardial or mid-wall, inferolateral LGE is myocarditis; subendocardial, coronary-territory LGE is ischaemia. CMR also flags pericardial involvement (perimyocarditis), RV involvement, intracardiac thrombus, and the oedema burden — larger oedema predicts worse outcome.[5]

Endomyocardial biopsy — the when-it-changes-management rule

Endomyocardial biopsy is the gold standard, but it is selective — biopsy when it changes management, not by reflex. The Dallas criteria read active myocarditis (infiltrate plus necrosis), borderline (infiltrate alone), or no myocarditis; immunohistochemistry raises sensitivity with CD3+ T lymphocytes and CD68+ macrophages (at least 14 cells per mm squared for active) and HLA class II upregulation; PCR on biopsy detects viral genome (PVB19, enterovirus, adenovirus, HHV-6, EBV, CMV), and viral persistence influences prognosis.[8]

Biopsy is recommended (ESC and AHA consensus) in the situations where the histological answer changes the next step:[2][8]

• Fulminant or rapidly progressive heart failure — suspect giant cell, which needs immunosuppression.
• New, unexplained sustained ventricular arrhythmia or high-grade AV block — suspect giant cell or sarcoid.
• Refractory cardiogenic shock being considered for mechanical circulatory support or transplant.
• Suspected eosinophilic, hypersensitivity or drug-induced myocarditis — confirm, stop the drug, give steroids.
• Deteriorating inflammatory cardiomyopathy where immunosuppression is being considered.[1]

Routine biopsy is NOT required for typical, mild lymphocytic myocarditis where CMR has comfortably established the diagnosis and the patient is haemodynamically stable. Biopsy has a price — perforation, tamponade, tricuspid regurgitation — so spend it where it pays.[1]

The classic trap — pericarditis-shaped, but NSAIDs harm

Everyone reaches for ibuprofen because the picture is pericarditis-shaped. That is how you worsen the myocarditis. NSAIDs are first-line in pericarditis and central to its management — and they are harmful in myocarditis with LV dysfunction, where they raise blood pressure, retain sodium, worsen inflammation, and are associated with worse outcomes.[2]

[2]

One-line discriminator: pain and diffuse ST elevation with a normal LV — pericarditis, NSAIDs fine; any LV dysfunction or troponin leak — myocarditis, NSAIDs out, paracetamol in. When the two overlap as perimyocarditis, treat the pericardial inflammation with colchicine but hold the NSAIDs if LV function is impaired.[1]

Other drug-class caveats during the acute phase: avoid high-dose digoxin (pro-arrhythmic in inflamed myocardium) and class Ic anti-arrhythmics in structurally abnormal hearts; introduce beta-blockers and ACE inhibitors cautiously — start them once the patient is stabilising, not in the haemodynamically unstable acute phase.[2]

Resuscitation — fulminant first, support the rest

ABCDE first. Oxygen only if hypoxic — target SpO2 94 to 98 percent (or 88 to 92 percent in COPD or risk of CO2 retention).[2]

Cardiogenic shock or fulminant myocarditis is the resuscitation problem — and the one where early mechanical support buys recovery.[4][7]

• Two large-bore cannulae, arterial and central lines, urinary catheter, continuous ECG, pulse oximetry, lactate trend.
• Inotropes and vasopressors — dobutamine 2 to 20 microgram per kg per min IV (beta-1 agonist, supports the failing LV) and/or milrinone 0.125 to 0.75 microgram per kg per min (PDE3 inhibitor, useful when tachyarrhythmia limits a beta-agonist); add noradrenaline 0.05 to 1 microgram per kg per min for vasoplegia.
• Mechanical circulatory support — escalate early in fulminant disease: intra-aortic balloon pump, Impella (percutaneous axial-flow LV assist), veno-arterial ECMO. Each buys time for the inflamed myocardium to recover.
• Diurese the overloaded patient — IV furosemide 20 to 40 mg bolus (or infusion) to relieve pulmonary congestion; non-invasive ventilation (CPAP or BiPAP) for pulmonary oedema.
• Treat arrhythmias per ACLS — DC cardioversion for unstable VT or VF; correct electrolytes (potassium 4.0 to 5.0 mmol per litre, magnesium at least 2.0); temporary transvenous pacing for symptomatic high-grade AV block.
• Anticoagulate if there is LV thrombus or severe LV dysfunction with a large apical akinetic region (prophylactic LMWH or heparin).
• Admit to ICU or CCU, with urgent cardiology and — if fulminant — heart-failure or transplant team referral.[1]

Activity restriction starts now. Strict bed rest in the acute phase, and no exercise — exertion during viraemia and inflammation markedly increases the sudden-death risk and extends the injury.[2]

Definitive care — support almost everyone, immunosuppress the few

There is no proven antiviral or anti-inflammatory therapy for typical lymphocytic myocarditis. Definitive management is aetiology-driven and supportive, and the immunosuppression decision is the single most tested fork.[2][4]

Step 1 — supportive heart-failure therapy, for every phenotype (once haemodynamically stable):[2][4]

• ACE inhibitor or ARNI — ramipril 1.25 to 10 mg PO once daily, titrated; or sacubitril/valsartan 24/26 to 97/103 mg PO twice daily. Reduces afterload, opposes adverse remodelling.
• Beta-blocker — bisoprolol 1.25 to 10 mg PO once daily, or carvedilol 3.125 to 25 mg PO twice daily. Introduced only after decongestion and stability; reduces arrhythmia and sudden death.
• MRA — spironolactone 12.5 to 50 mg PO once daily (or eplerenone 25 to 50 mg) if LVEF under 35 percent or symptomatic HF.
• Loop diuretic — furosemide 20 to 80 mg PO or IV for congestion; de-escalate as the patient dries out.
• SGLT2 inhibitor — dapagliflozin 10 mg PO once daily or empagliflozin 10 mg PO once daily, per recent HF guidelines, once stable.
• Treat arrhythmia — rate control for AF (beta-blocker); anticoagulation (DOAC or warfarin) if AF, LV thrombus, or severe LV dysfunction with apical akinesia.
• Avoid NSAIDs. Paracetamol for fever and pain.[1]

Step 2 — phenotype-specific therapy: the immunosuppression face-off.[4]

[8]

One-line discriminator: lymphocytic — support only; giant cell, eosinophilic, or sarcoid — immunosuppress. Get the biopsy before you commit either way in the fulminant or arrhythmic case.[4]

The giant cell regimen, verbatim: cyclosporine (target trough 200 to 300 nanogram per mL initially) combined with corticosteroids — methylprednisolone 0.5 to 1 g IV daily for 3 days, then prednisolone 1 mg per kg per day tapering — plus or minus azathioprine or mycophenolate. Without therapy, death is nearly universal within months; treated survival extends to years, and giant cell can even recur in the transplanted heart with survival still good.[10]

Step 3 — mechanical circulatory support and transplant. Refractory cardiogenic shock in fulminant myocarditis (especially giant cell) is the indication for VA-ECMO, Impella or surgical LVAD as a bridge to decision, bridge to recovery, or bridge to transplant. Transplantation is reserved for irreversible end-stage inflammatory cardiomyopathy.[4]

Specific causes — name the bug, change the drug

Several causes have a specific antidote, and naming the organism changes the prescription. Memorise them as a cluster — each is a one-line viva answer.[3]

• Lyme carditis with high-grade AV block — IV ceftriaxone 2 g once daily (or oral doxycycline 100 mg twice daily for milder disease) for 14 to 21 days, plus temporary pacing for symptomatic block. Usually fully reversible.[4]
• Chagas myocarditis — benznidazole 5 to 8 mg per kg per day orally for 60 days (or nifurtimox) for acute or recent infection; manage chronic Chagas cardiomyopathy with standard HF therapy.[3]
• Diphtheritic myocarditis — equine diphtheria antitoxin IV or IM urgently, plus penicillin G or erythromycin; supportive HF care; preventable by vaccination.[3]
• Clozapine-induced (eosinophilic) myocarditis — incidence about 1 percent, monitor troponin and CRP during titration; stop the drug and give systemic corticosteroids. Outcome usually good if recognised early.[4]
• mRNA COVID-19 vaccine-associated myocarditis — chest pain within about a week of vaccination, raised troponin, commonest after the second dose in young males (peak 16 to 24 years), population rate roughly 10 to 100 per million doses. Usually mild and self-limiting, managed supportively — and the myocarditis risk from COVID-19 infection itself is substantially higher, supporting continued vaccination.[4]

A few more that change the plan: anthracycline cardiotoxicity (doxorubicin, daunorubicin) is dose-dependent — keep the cumulative lifetime doxorubicin dose below 400 to 450 mg per metre squared, monitor with serial echo and troponin, and use dexrazoxane for cardioprotection. Trastuzumab causes a usually reversible cardiomyopathy. Cocaine causes coronary spasm, ischaemia and direct myocyte toxicity. Perimyocarditis is treated with colchicine 0.5 mg once or twice daily for 3 months plus or minus aspirin 750 to 1000 mg every 8 hours for 1 to 2 weeks tapering — but hold the NSAIDs if LV function is impaired.[1][3]

Giant cell myocarditis — the triad you must not miss

This is the one not to miss, and it announces itself in a triad that should trigger urgent biopsy on the spot. Rapidly progressive heart failure plus sustained ventricular tachycardia plus high-grade AV block, in a patient in middle age (median forties), often with another autoimmune disease (thyroiditis, myasthenia, ulcerative colitis) — that is giant cell myocarditis until the biopsy says otherwise.[10][4]

Histology shows multinucleated giant cells on a background of necrosis and inflammation. Urgent endomyocardial biopsy, then cyclosporine plus corticosteroid — the combination transforms prognosis. Untreated, median survival is around 11 months; treated, survival extends to years.[10]

Why this matters more than any other single fact on the page: giant cell myocarditis is one of the few causes of myocarditis where a specific therapy changes the outcome, and the window is short. A fulminant or arrhythmic case biopsied late is a case biopsied too late.[4]

The fulminant paradox — sickest-looking, best prognosis

The fulminant paradox is exam gold, and it inverts every instinct you have about how sick patients do. The patient who looks the worst — cardiogenic shock within days of a viral illness, severe global LV dysfunction on echo — has the better long-term prognosis if you support them through the acute phase, often with VA-ECMO.[7]

[7]

The echo discriminator — the single feature that earns the label — is the severe global dysfunction with a non-dilated, thick-walled (oedematous) ventricle, against the dilated thin-walled ventricle of acute non-fulminant disease. Get the echo right and you have called the prognosis.[7]

No sport for three to six months — the modifiable sudden-death risk

Exercise during recovery is the single modifiable sudden-death risk in myocarditis, and the restriction is non-negotiable. No competitive sport and no moderate-to-vigorous exercise for 3 to 6 months after diagnosis, by both ESC and AHA recommendation; strict bed rest in the acute phase.[2][4]

Return-to-play — the five-criteria number rule (after 3 to 6 months):[2][4]

1. Clinical recovery — asymptomatic.
2. Normal serum biomarkers — troponin and BNP back to normal.
3. Normal resting ECG — or stable, with no new arrhythmia on Holter.
4. Normal biventricular systolic function on echo or CMR.
5. No significant arrhythmia on exercise testing and ambulatory monitoring.[1]

All five, or no return to play. Athletes carry a disproportionate sudden-death risk, and exertion during viraemia worsens injury — so the restriction is the intervention, not a footnote.[2]

How patients come to harm — the preventable list

• Treating myocarditis with NSAIDs because it looks like pericarditis — the recurring trainee error, and it worsens the myocarditis.[2]
• Missing giant cell myocarditis by not biopsying a fulminant, arrhythmic, or heart-block case — a treatable disease left untreated.[4]
• Mislabelling myocarditis as mild ACS with normal coronaries and discharging the patient to sport — risking sudden death.[3]
• Failing to restrict activity for 3 to 6 months — the single modifiable sudden-death risk.[2]
• Stopping an ACE inhibitor or beta-blocker for acute hypotension instead of recognising fulminant disease and escalating to inotropes and MCS.[4]
• Giving immunosuppression to typical lymphocytic myocarditis — the Myocarditis Treatment Trial showed no benefit.[8]
• Not stopping clozapine when troponin rises during titration (eosinophilic myocarditis).[4]
• Forgetting Lyme in AV block with tick exposure and erythema chronicum migrans.[1]

The complications to watch for: heart failure (acute and chronic), progression to dilated cardiomyopathy (roughly 5 to 10 percent of biopsy-proven myocarditis), arrhythmia (atrial fibrillation, VT, VF, AV block), sudden cardiac death (especially athletes), cardiogenic shock in fulminant disease, intracardiac thrombus and systemic embolism, pericardial effusion and tamponade in perimyocarditis, and recurrence.[2]

Prognosis and disposition

Most patients with mild lymphocytic myocarditis recover fully within weeks to months. The fulminant paradox — 93 percent versus 45 percent transplant-free survival at 11 years — is the one number to carry. Predictors of poor outcome: reduced LVEF (under 40 percent), persistent LV dysfunction, LV dilatation, heart failure at presentation, sustained ventricular arrhythmia, syncope or prior sudden death, giant cell histology, persistent viral genome, advanced NYHA class, raised BNP, renal dysfunction, larger LGE extent on CMR, older age, and comorbidity.[7][2][4]

Disposition follows severity, not the label:[2]

• Mild, haemodynamically stable, normal echo — ward-level monitoring, telemetry, supportive therapy; discharge when stable with strict activity restriction and early cardiology follow-up with repeat echo or CMR.
• LV dysfunction, arrhythmia, or significant symptoms — CCU or high-dependency; consider transfer to a heart-failure centre.
• Fulminant disease, cardiogenic shock, sustained VT, high-grade AV block — ICU, mechanical circulatory support, urgent cardiology and heart-failure or transplant referral, and endomyocardial biopsy.[1]

Follow up with serial echocardiography plus or minus CMR at 1 to 3 months and again at 6 months; trend troponin and BNP; Holter for arrhythmia; assess return-to-play criteria in athletes.[4]

Special populations

• Athletes — disproportionate sudden-death risk; no competitive sport or moderate-to-vigorous exercise for 3 to 6 months; return-to-play only when all five criteria are met.[2]
• Children — important cause of paediatric heart failure and sudden death; more often PCR-positive; can present as non-specific respiratory or gastrointestinal illness with tachypnoea, hepatomegaly, poor feeding. High index of suspicion, aggressive supportive care, paediatric cardiology and transplant referral for refractory cases.[4]
• Pregnancy and peripartum — overlaps with peripartum cardiomyopathy (last month of pregnancy to 5 months postpartum); both produce LV dysfunction and thromboembolism; use pregnancy-safe HF therapy (avoid ACEi, ARNI and MRA in pregnancy; hydralazine plus nitrates plus beta-blocker; bromocriptine is emerging for peripartum cardiomyopathy).[4]
• Elderly — presentation dominated by heart failure rather than chest pain; comorbid ischaemic heart disease complicates interpretation; lower threshold for coronary angiography.[2]
• Immunocompromised (HIV, transplant, chemotherapy) — atypical organisms (CMV, Toxoplasma, fungal, bacterial); broader PCR and microbiology; biopsy often required; aggressive opportunistic-infection treatment.[1]
• Anticoagulated patients — continue therapeutic anticoagulation; intracardiac thrombus and embolic events warrant intensification.[1]

Guidelines, trials and regional deltas worth naming

The 2025 ESC Guidelines for the management of myocarditis and pericarditis (Schulz-Menger et al.) are the most current European guidance, consolidating the 2018 Lake Louise Criteria, the role of EMB, and the phenotype-based management approach.[1]

The 2013 ESC position statement (Caforio et al.) was the prior benchmark, defining the syndromic diagnosis and the role of CMR and biopsy. The 2020 Expert Consensus (Ammirati et al.) gives a practical phenotype-based algorithm and defines when immunosuppression is justified.[2][4]

The Lake Louise lineage: the 2009 JACC White Paper (Friedrich et al.) standardised CMR diagnosis; the 2018 update (Ferreira et al.) added parametric T1 and T2 mapping. The 2007 AHA, ACC and ESC Scientific Statement (Cooper et al.) defines the role and technique of endomyocardial biopsy. The 1995 Myocarditis Treatment Trial (Mason et al.) is the landmark negative trial — immunosuppression did not improve typical lymphocytic myocarditis — establishing supportive care as the default.[6][5][8]

Regional deltas:[2][4]

• Developed world — viral causes predominate (PVB19 commonest PCR-positive, then enteroviruses, adenovirus, HHV-6).
• Latin America — Chagas disease (Trypanosoma cruzi) is the commonest cause of myocarditis-related cardiomyopathy; treat with benznidazole or nifurtimox.
• Africa and South Asia — rheumatic carditis (post-streptococcal, predominantly in children and young adults) sits in the differential; diphtheria persists in under-immunised populations; HIV-related myocarditis where prevalence is high.
• mRNA COVID-19 vaccine programmes — vaccine-associated myocarditis must be balanced against the higher myocarditis risk from COVID-19 itself.[1]

The mantra

Troponin up, coronaries clean, MRI for the call — support, do not immunosuppress unless it is giant cell — and no sport for three to six months.[1][2]

Ward-round test — three stems, thirty seconds each

Stem 1 — young man, viral prodrome, chest pain, troponin up, ST elevation, normal coronaries

A 24-year-old man presents with pleuritic chest pain, palpitations and a flu-like illness a week ago. Troponin is 900 nanogram per litre, ECG shows widespread concave ST elevation with PR depression, and coronary angiography is normal. What is the diagnosis, and what do you do next? Model: This is myocarditis (perimyocarditis phenotype) — chest pain plus raised troponin plus ST changes plus normal coronaries is the triage fork. Confirm with cardiac MRI using the Lake Louise Criteria (at least one T2-based and one T1-based criterion; subepicardial or mid-wall inferolateral LGE is the discriminator from ischaemic subendocardial LGE). Treat supportively — heart-failure therapy if there is LV dysfunction, paracetamol not NSAIDs, strict bed rest, and no sport for 3 to 6 months with return-to-play only when all five criteria are met. No immunosuppression for typical lymphocytic disease; biopsy only if the course turns fulminant or arrhythmic.[1][5]

Stem 2 — fulminant myocarditis, shock, thick-walled non-dilated LV

A 30-year-old woman is in cardiogenic shock two days after a viral illness. Echo shows severe global LV dysfunction with a thick-walled, non-dilated ventricle. Lactate is rising on inotropes. What is the disposition, and what should you tell the family about prognosis? Model: This is fulminant myocarditis — ICU now, escalate early to VA-ECMO (or Impella) as bridge to recovery, inotropes (dobutamine, milrinone) and vasopressors (noradrenaline) as needed, urgent heart-failure or transplant referral, and endomyocardial biopsy to exclude giant cell. The family message carries the fulminant paradox: despite looking the sickest, supported fulminant myocarditis has better long-term survival than non-fulminant — McCarthy 2000 showed 93 percent transplant-free survival at 11 years versus 45 percent. Support hard, do not despair.[7][4]

Stem 3 — middle-aged, rapid heart failure plus sustained VT plus complete heart block

A 45-year-old man presents over a week with rapidly progressive heart failure, an episode of sustained VT, and now complete heart block on the monitor. What is the diagnosis, the next investigation, and the treatment that changes prognosis? Model: This is the giant cell myocarditis triad — rapidly progressive heart failure plus sustained VT plus high-grade AV block in middle age. The next investigation is urgent endomyocardial biopsy (multinucleated giant cells on histology), and the treatment that changes prognosis is cyclosporine plus corticosteroid (cyclosporine trough 200 to 300 nanogram per mL initially; methylprednisolone 0.5 to 1 g IV daily for 3 days then prednisolone 1 mg per kg per day tapering). Untreated median survival is about 11 months; treated survival extends to years. This is the one not to miss.[10][4]

References

1. [1]Schulz-Menger J, Collini V, Gröschel J, et al. 2025 ESC Guidelines for the management of myocarditis and pericarditis Eur Heart J, 2025.PMID 40878297
2. [2]Caforio AL, Pankuweit S, Arbustini E, et al. Current state of knowledge on aetiology, diagnosis, management, and therapy of myocarditis: a position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases Eur Heart J, 2013.PMID 23824828
3. [3]Sagar S, Liu PP, Cooper LT Jr. Myocarditis Lancet, 2012.PMID 22185868
4. [4]Ammirati E, Frigerio M, Adler ED, et al. Management of Acute Myocarditis and Chronic Inflammatory Cardiomyopathy: An Expert Consensus Document Circ Heart Fail, 2020.PMID 33176455
5. [5]Ferreira VM, Schulz-Menger J, Holmvang G, et al. Cardiovascular Magnetic Resonance in Nonischemic Myocardial Inflammation: Expert Recommendations J Am Coll Cardiol, 2018.PMID 30545455
6. [6]Friedrich MG, Sechtem U, Schulz-Menger J, et al. Cardiovascular magnetic resonance in myocarditis: A JACC White Paper J Am Coll Cardiol, 2009.PMID 19389557
7. [7]McCarthy RE 3rd, Boehmer JP, Hruban RH, et al. Long-term outcome of fulminant myocarditis as compared with acute (nonfulminant) myocarditis N Engl J Med, 2000.PMID 10706898
8. [8]Cooper LT, Baughman KL, Feldman AM, et al. The role of endomyocardial biopsy in the management of cardiovascular disease: a scientific statement from the American Heart Association, the American College of Cardiology, and the European Society of Cardiology. Endorsed by the Heart Failure Society of America and the Heart Failure Association of the European Society of Cardiology J Am Coll Cardiol, 2007.PMID 17980265
9. [9]Biesbroek PS, Beek AM, Germans T, et al. Diagnosis of myocarditis: Current state and future perspectives Int J Cardiol, 2015.PMID 25974197
10. [10]Okura Y, Dec GW, Hare JM, et al. A clinical and histopathologic comparison of cardiac sarcoidosis and idiopathic giant cell myocarditis J Am Coll Cardiol, 2003.PMID 12535829