Myocarditis is inflammation of the myocardium, often caused by viral infections, leading to cardiac dysfunction that can manifest as heart failure, arrhythmias, or sudden cardiac death.

Exam domain	One-glance essentials
Definition / diagnosis	Myocarditis = non-ischaemic inflammatory disease of myocardium; dysfunction defines inflammatory cardiomyopathy ^[2] Clinical spectrum: ACS-like illness, new HF, arrhythmia, shock or sudden death ^[2]
Epidemiology / risks	Viral disease predominates locally; *adenovirus, echovirus and Coxsackie virus* are highlighted in teaching ^[1] Also consider drug/hypersensitivity, autoimmune, giant-cell, eosinophilic and sarcoid causes ^[2]
Core mechanism	Trigger → direct injury → immune-mediated myocyte damage/molecular mimicry → oedema and necrosis ^[2] Persistent inflammation → fibrosis/remodelling → dilated cardiomyopathy and re-entry arrhythmias ^[2]
Clinical picture	*Recent flu-like illness with fever, arthralgia and malaise* followed by dyspnoea, palpitations or syncope ^[1] Tachycardia out of proportion to fever, S3, displaced apex and functional MR suggest pump failure ^[2] Chest pain usually reflects concomitant pericarditis ^[2]
Investigations	ECG may show non-specific ST/T changes, VT or heart block and can mimic MI/pericarditis ^[1] Echo assesses LVEF/RWMA; exclude obstructive CAD, then use CMR Lake Louise criteria ^[2] *Endomyocardial biopsy is the gold standard but reserved for cases where histology changes treatment* ^[1]
Management	*Viral/lymphocytic myocarditis: supportive care and standard HF/arrhythmia treatment* ^[1] *No exercise for 3–6 months*; monitor rhythm and ventricular recovery ^[3] Fulminant shock → inotropes and mechanical support; immunosuppression only for selected histologies ^[2]
Complications	VT/VF, AV block and sudden cardiac death may occur even with modest symptoms ^[2] Acute HF/shock or chronic dilated cardiomyopathy with thromboembolism may follow ^[2]
Prevention / follow-up	Avoid strenuous activity until symptoms, ventricular function, biomarkers and rhythm assessment recover ^[3] Remove offending drugs/toxins and treat specific infection or autoimmune disease when identified ^[2]
Exam traps	Troponin may be normal; absence does not exclude myocarditis ^[1] Myocarditis CMR: subepicardial/mid-wall LGE; MI: subendocardial/transmural coronary distribution ^[2] *Avoid NSAIDs when myocardial involvement/LV dysfunction predominates* ^[1]

References

^[1] Lecture slides: Three Cases SOB 20211.pdf ^[2] Senior notes: Ryan Ho Cardiology.pdf ^[3] Lecture slides: GC 069. Inherited Cardiac conditions.pdf

Myocarditis

Myocarditis is an inflammatory disease of the myocardium — that is, the muscular layer of the heart wall — resulting from pathological immune processes triggered by a variety of etiologies ^[1]^[2]. Breaking down the name: "myo-" (Greek: mys = muscle) + "-card-" (Greek: kardia = heart) + "-itis" (Greek: = inflammation). So the term literally means inflammation of the heart muscle.

Key conceptual distinctions:

Myocarditis is defined as non-ischaemic myocardial inflammation ^[3] — this separates it from myocardial injury due to coronary artery disease (where the problem is supply-demand mismatch, not primary inflammation).
Inflammatory cardiomyopathy is defined as myocarditis accompanied by cardiac dysfunction, which can lead to dilated cardiomyopathy (DCM) in the long run ^[1]^[2]. Think of it as a spectrum: myocarditis is the acute insult; if it causes lasting ventricular remodelling and systolic dysfunction, it becomes inflammatory cardiomyopathy → DCM.
Myocarditis is one of the major causes of sudden, unexpected death in adults < 40 years (~20% of cases of sudden cardiac death in young adults) ^[4].

Key Concept

Myocarditis per se is usually asymptomatic. When chest pain is present, it usually reflects concomitant pericarditis (i.e., myopericarditis). The myocardial inflammation itself causes pump failure and electrical instability, not chest pain per se — pain receptors are in the pericardium, not the myocardium ^[4].

2. Epidemiology

True incidence is difficult to estimate because many cases are subclinical or misdiagnosed. Autopsy series suggest myocarditis in 1–9% of routine post-mortem examinations.
Estimated global incidence: ~10–22 cases per 100,000 persons per year.
Accounts for approximately 10–20% of sudden cardiac death in young adults and athletes under 40 years old.
It is an important cause of new-onset, unexplained heart failure — approximately 9% of dilated cardiomyopathy cases are attributed to prior myocarditis ^[4].

Factor	Details
Age	Any age; peak in young adults (20–40 years) and neonates/infants
Sex	Male > Female (~1.5–2:1) — possibly because testosterone upregulates viral receptors (CAR) and suppresses anti-inflammatory pathways
Geography	Viral causes predominate in North America, Europe, and East Asia (including Hong Kong). Chagas disease (Trypanosoma cruzi) dominates in South America. Diphtheria-related myocarditis remains relevant in non-immunized populations ^[5]

In Hong Kong, as in other developed regions, viral myocarditis is the most common form.
Most common causes in Northern America and Europe (and Hong Kong): Adenovirus, Echovirus, and Coxsackie virus ^[5].
Rest of the World: Trypanosoma cruzi (Chagas disease) and Corynebacterium diphtheriae (Diphtheria) — very common in South America ^[5].
COVID-19-associated myocarditis became a recognized entity during the pandemic, with cardiac MRI showing involvement in up to 78% of recovered patients with ongoing inflammation in 60% ^[6].
Post-mRNA-vaccination myocarditis (particularly with BNT162b2/Comirnaty and mRNA-1273) was recognized as a rare adverse event, predominantly in young males after the second dose, presenting 2–5 days post-vaccination. This is typically self-limiting and mild.

High Yield — HKUMed Exam Framing

In Hong Kong, the most common causes of myocarditis are viral — particularly Adenovirus, Echovirus, and Coxsackie virus ^[5]. This matches the GC lecture slide framing. Know the geographic variation: South America = Chagas; developing countries = Diphtheria.

3. Anatomy and Function — The Myocardium

To understand why myocarditis causes such diverse clinical manifestations, you need to understand what the myocardium does:

The heart wall has three layers (from inside out):

Endocardium — thin inner lining (endothelial cells + subendocardial connective tissue)
Myocardium — the thick muscular layer, composed of:
- Cardiomyocytes: contractile cells arranged in a spiral pattern, connected by intercalated discs containing gap junctions (allow electrical coupling) and desmosomes (mechanical coupling)
- Conduction system cells: specialized cardiomyocytes (SA node, AV node, His bundle, bundle branches, Purkinje fibres)
- Interstitium: fibroblasts, collagen, and capillary network
Epicardium (visceral pericardium) — outermost layer continuous with the pericardial sac

The myocardium is responsible for:

Function	Clinical consequence when inflamed
Contraction (systolic function)	Myocyte necrosis/oedema → ↓contractility → ↓LVEF → heart failure
Relaxation (diastolic function)	Oedema/fibrosis → ↑stiffness → ↓compliance → diastolic dysfunction
Electrical conduction	Inflammation/oedema of conduction tissue → heart block, arrhythmias
Structural integrity	Myocyte death + oedema → ventricular dilatation → functional MR/TR

This explains why myocarditis can present as heart failure, arrhythmia, ACS-mimic, or sudden death — depending on which function is most disrupted.

4. Etiology

The causes of myocarditis are best organized into infectious and non-infectious categories ^[1]^[2]^[3]^[4].

4.1 Infectious Causes

Viral myocarditis is the single most common etiology in developed countries including Hong Kong.

Virus Family	Specific Agents	Notes
Enterovirus	Coxsackie B (most classic), Echovirus, Poliovirus	Historically the #1 cause; tropism for cardiomyocytes via the Coxsackievirus-Adenovirus Receptor (CAR)
Adenovirus	Adenovirus types 2, 5	Also binds CAR; now recognized as equally common as Coxsackie
Erythrovirus	Parvovirus B19	Does NOT infect cardiomyocytes — infects endothelial cells → endothelial dysfunction + inflammatory infiltrate
Herpesvirus	CMV, EBV, HHV-6, HSV, VZV	HHV-6 and Parvovirus B19 are the most common in recent endomyocardial biopsy (EMB) studies in Europe
Orthomyxovirus	Influenza A/B	Myocarditis complicates ~5–10% of severe influenza
Paramyxovirus	Mumps, Measles	Rare now due to vaccination
Retrovirus	HIV	Can cause direct or immune-mediated myocardial injury
Hepatitis virus	HCV	Associated with chronic myocarditis/DCM
Coronavirus	SARS-CoV-2	Significant cause during COVID-19 pandemic; mechanism includes direct invasion and immune-mediated injury ^[6]

The most common causes of myocarditis in Hong Kong (and North America/Europe) are Adenovirus, Echovirus, and Coxsackie virus ^[5].

Category	Examples
Pyogenic	Staphylococcus, Streptococcus
Atypical	Mycoplasma, Chlamydia, Rickettsia (Q fever, RMSF)
Spirochetes	Borrelia burgdorferi (Lyme disease — causes AV block classically), Treponema pallidum (syphilis), Leptospira
Mycobacterial	M. tuberculosis
Toxin-producing	Corynebacterium diphtheriae — exotoxin directly damages myocardium
Enteric	Salmonella typhi (typhoid fever)

Candida, Aspergillus, Cryptococcus, Histoplasma
Primarily in immunocompromised patients

Agent	Disease	Notes
Trypanosoma cruzi	Chagas disease	Most important cause worldwide; endemic to Central/South America. Causes chronic cardiomyopathy decades after initial infection
Plasmodium spp.	Malaria	Rare myocardial involvement
Toxoplasma gondii	Toxoplasmosis	In immunocompromised

4.2 Non-Infectious Causes

Category	Examples	Mechanism
Autoimmune	Rheumatoid arthritis, SLE, GPA (Granulomatosis with Polyangiitis)	Immune complex deposition, vasculitis of intramyocardial vessels
Granulomatous	Sarcoidosis	Non-caseating granulomas in myocardium → conduction defects + regional wall motion abnormalities
Giant cell myocarditis	Idiopathic	Multinucleated giant cells + lymphocytic infiltrate; fulminant course, rapidly fatal without immunosuppression or transplant
Eosinophilic myocarditis	Hypereosinophilic syndrome, Churg-Strauss (EGPA)	Eosinophilic infiltration → myocyte damage via eosinophilic granule proteins
Acute rheumatic fever	Post-GAS infection	Molecular mimicry → pancarditis (endo + myo + pericardium) ^[7]

Agent	Mechanism
Doxorubicin (anthracycline)	Dose-dependent cardiotoxicity via free radical generation → cumulative myocyte death (Type I — irreversible)
Trastuzumab (Herceptin)	HER2 blockade on cardiomyocytes → ↓survival signalling (Type II — often reversible)
Cocaine	Sympathomimetic → coronary vasospasm + direct myocyte toxicity
Alcohol	Direct toxic effect on mitochondria + nutritional deficiency (thiamine)
Immune checkpoint inhibitors (ICIs)	Pembrolizumab, Nivolumab, Ipilimumab → fulminant lymphocytic myocarditis (1–2% incidence, high mortality ~25–50%)
Others	Methyldopa, penicillins, sulphonamides, lithium

Usually drug-related (e.g., methyldopa, penicillins, sulphonamides) ^[4]
S/S: acute rash, fever, peripheral eosinophilia, ECG abnormalities ± sudden cardiac death or rapidly progressive heart failure ^[4]
Mechanism: Type I or IV hypersensitivity → eosinophilic/lymphocytic myocardial infiltration

Radiation exposure (radiation-induced myocarditis)
Carbon monoxide poisoning
Hydrocarbon and arsenic exposure ^[1]^[2]
Snake/insect bites ^[3]

Etiology Summary — Mnemonic: 'VITAMIN CD'

V — Viral (most common)
I — Immune/autoimmune (SLE, RA, sarcoidosis, giant cell)
T — Toxic (alcohol, cocaine, carbon monoxide)
A — Allergic/hypersensitivity (drugs, insect bites)
M — Medications (doxorubicin, trastuzumab, checkpoint inhibitors)
I — Infectious non-viral (bacterial, fungal, parasitic)
N — Non-classified (idiopathic)
C — COVID-19/post-vaccination
D — Diphtheria (exam favourite for non-immunised populations)

5. Pathophysiology

Understanding the pathophysiology of myocarditis requires thinking in phases. The best-characterized model is viral myocarditis, which proceeds through three overlapping phases:

Viral entry: Cardiotropic viruses (e.g., Coxsackie B, Adenovirus) bind to specific surface receptors on cardiomyocytes:
- Coxsackievirus-Adenovirus Receptor (CAR): a transmembrane protein normally involved in cell-cell adhesion at intercalated discs
- Decay-Accelerating Factor (DAF/CD55): a complement regulatory protein — used as co-receptor
- Parvovirus B19 uniquely targets endothelial cells (not myocytes) via globoside (P antigen) → endothelial dysfunction and secondary ischaemia
Direct cytopathic effect: Viral replication within myocytes → disruption of cytoskeletal proteins (dystrophin is cleaved by enteroviral protease 2A) → myocyte necrosis and release of intracellular contents (troponin, CK).
Innate immune activation: Damage-associated molecular patterns (DAMPs) from necrotic myocytes + pathogen-associated molecular patterns (PAMPs) activate:
- Toll-like receptors (TLRs) on resident macrophages and dendritic cells
- NK cell killing of infected myocytes
- Type I interferon response → antiviral state

T-cell mediated immunity:
- Dendritic cells present viral antigens (and also exposed self-antigens like cardiac myosin, released from damaged myocytes) to CD4+ and CD8+ T cells
- CD8+ cytotoxic T cells kill virus-infected myocytes (this is necessary to clear virus but also causes collateral damage — the classic "friendly fire" problem)
- CD4+ helper T cells activate B cells to produce neutralizing antibodies
Molecular mimicry: This is the critical concept — viral antigens share structural homology with cardiac proteins:
- Coxsackie B → shares epitopes with cardiac myosin heavy chain
- Antibodies and T cells raised against viral antigens cross-react with host cardiac proteins
- This is exactly the same mechanism as in acute rheumatic fever (where anti-M protein antibodies from GAS cross-react with cardiac proteins) ^[7]
Cytokine storm: Pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, IFN-γ) amplify inflammation → further myocyte damage + interstitial oedema

If immune response is effective and proportionate:
- Virus is cleared, inflammation resolves
- Myocyte regeneration is limited (cardiomyocytes have very low proliferative capacity)
- Fibrosis replaces necrotic areas → may be clinically silent or cause minor residual dysfunction
- Most patients recover at this stage
If immune response is excessive or persistent:
- Ongoing autoimmune attack (antibodies against cardiac myosin, β1-adrenergic receptors, etc.)
- Persistent viral genome in myocardium (viral persistence without active replication)
- Progressive myocyte loss → ventricular dilatation → neurohormonal activation (RAAS, SNS) → further remodelling
- End result: dilated cardiomyopathy (DCM) — this is the myocarditis → DCM pathway that accounts for ~9% of DCM ^[4]
Fibrosis and electrical remodelling:
- Patchy fibrosis disrupts the normal electrical syncytium → creates re-entry circuits → ventricular arrhythmias
- Inflammatory oedema/granulomas in the conduction system → AV block (especially in Lyme disease, sarcoidosis, giant cell myocarditis)

Etiology	Specific Mechanism
Coxsackie B	Binds CAR → direct cytolysis + molecular mimicry with cardiac myosin
Parvovirus B19	Infects endothelial cells → endothelial dysfunction + microvascular ischaemia (not direct myocyte infection)
Chagas disease	T. cruzi amastigotes replicate inside cardiomyocytes → chronic inflammation → mega-organs; also autoimmune against cardiac antigens
Diphtheria	Exotoxin inhibits protein synthesis (via ADP-ribosylation of EF-2) → direct myocyte death
Giant cell myocarditis	Idiopathic; multinucleated giant cells with CD4+ T cells → fulminant destruction
Sarcoidosis	Non-caseating granulomas → conduction system involvement → AV block; also regional wall motion abnormalities mimicking MI
Checkpoint inhibitors	Removal of immune checkpoint (PD-1/CTLA-4) brakes → unrestrained T-cell activation against cardiac antigens
COVID-19	Multiple mechanisms: direct cardiomyocyte infection via ACE2, cytokine storm, endothelial dysfunction, microthrombi ^[6]

Why Can Myocarditis Cause Sudden Death?

Students often focus only on heart failure. But arrhythmia is the leading cause of death in acute myocarditis. Inflamed, oedematous, necrotic myocardium creates electrical heterogeneity → re-entry circuits → VT/VF. This is why patients must avoid exertion — exercise increases catecholamines → ↑automaticity + ↑triggered activity in already unstable myocardium → potentially fatal ventricular arrhythmias ^[4].

6. Classification

Myocarditis can be classified by several schemes:

Type	Duration	Features
Acute myocarditis	Days to weeks	Active inflammation, may be fulminant or non-fulminant
Fulminant myocarditis	Days	Rapid onset of severe heart failure or cardiogenic shock within 2 weeks of viral prodrome; requires haemodynamic support; paradoxically has better long-term prognosis if patient survives the acute phase (because the vigorous immune response tends to clear the virus effectively)
Subacute/chronic myocarditis	Weeks to months	Insidious onset of DCM-like picture; more likely to progress to chronic DCM

The Dallas criteria remain the standard for histological classification of endomyocardial biopsy (EMB):

Category	Definition
Active myocarditis	Inflammatory cellular infiltrate with adjacent myocyte necrosis or degeneration (not typical of ischaemic damage)
Borderline myocarditis	Inflammatory infiltrate present but without myocyte necrosis
No myocarditis	No inflammatory infiltrate
Ongoing (persistent) myocarditis	On follow-up biopsy — continued active or borderline myocarditis
Resolving (healing) myocarditis	On follow-up biopsy — reduction in inflammatory infiltrate ± fibrosis
Resolved (healed) myocarditis	No inflammatory infiltrate; may have fibrosis

Pattern	Typical Causes	Prognosis
Lymphocytic	Viral (most common pattern), idiopathic	Variable; often self-limiting
Giant cell	Idiopathic (autoimmune), thymoma-associated	Poor — median survival 5.5 months without immunosuppression
Eosinophilic	Drug hypersensitivity, parasitic (Chagas, toxocariasis), hypereosinophilic syndrome, EGPA	Variable; remove trigger → often resolves
Granulomatous	Sarcoidosis, tuberculosis	Conduction defects prominent; may need pacemaker
Neutrophilic	Bacterial/fungal	Rare; suggests active infection

Pattern	Features
ACS-like	Acute chest pain following viral infection, ST/T changes, global/regional LV dysfunction ± ↑cTn
New-onset/worsening HF	SOB, oedema, chest discomfort, fatigue over weeks/months with ventricular dysfunction
Life-threatening	Sudden cardiac death, malignant arrhythmias, cardiogenic shock, ADHF

7. Clinical Features

The clinical presentation of myocarditis is highly variable, usually insidious and often asymptomatic ^[4]. This is one of the great diagnostic challenges — the spectrum ranges from completely subclinical to fulminant cardiogenic shock.

7.1 Symptoms

Viral prodrome: recent flu-like illness with fever, arthralgia, and malaise ^[4]
Usually occurs several weeks after initial viral symptoms ^[4]
Upper respiratory tract symptoms: sore throat, rhinorrhoea, cough
GI symptoms: nausea, vomiting, diarrhoea (especially with enteroviral infections)
Pathophysiological basis: This represents the initial systemic viraemia. The virus replicates in the pharynx/GI tract → disseminates haematogenously → reaches the myocardium. The cardiac symptoms lag because Phase 2 (immune-mediated injury) takes days to develop.

Symptom	Pathophysiological Basis
Chest pain	Usually reflects concomitant pericarditis (myopericarditis). The pericardium has somatic pain fibres (phrenic nerve C3-5); the myocardium itself is poorly innervated for pain. Chest pain may be pleuritic (worse with inspiration, relieved by sitting forward) or may mimic ACS (substernal, pressure-like) if there is significant myocardial oedema causing microvascular compression
Dyspnoea / SOB	Myocyte damage → ↓LV contractility → ↑LV end-diastolic pressure → pulmonary venous congestion → transudation into alveoli → impaired gas exchange ^[3]^[8]. This is the mechanism of acute heart failure
Orthopnoea and PND	Redistribution of blood from lower extremities to pulmonary vasculature when supine → further ↑pulmonary capillary pressure
Fatigue / exercise intolerance	↓CO → inadequate O₂ delivery to skeletal muscle → early anaerobic metabolism
Palpitations	Myocardial inflammation → electrical instability → arrhythmias (sinus tachycardia, atrial fibrillation, ventricular ectopics, VT) ^[4]
Syncope / pre-syncope	VT/VF → transient ↓↓cerebral perfusion; OR complete heart block → inadequate ventricular rate
Peripheral oedema	If RV also affected → ↑systemic venous pressure → transudation into interstitial space

Fever ^[3] — reflects systemic inflammatory response ± ongoing infection
Myalgia, arthralgia — viral prodrome or autoimmune association
Anorexia, weight loss — chronic inflammation + ↓CO → GI hypoperfusion

7.2 Signs

Sign	Pathophysiological Basis
Tachycardia (often out of proportion to fever) ^[3]	Compensatory SNS activation due to ↓CO. "Out of proportion to fever" is a clinical pearl: normally HR increases ~10 bpm per 1°C. In myocarditis, the tachycardia exceeds what the fever alone would explain because both fever AND pump failure drive heart rate up
Hypotension	↓CO → ↓MAP. May indicate cardiogenic shock in fulminant myocarditis
Low-grade fever	Systemic inflammation; higher fevers suggest ongoing active infection
Tachypnoea	Pulmonary congestion → stimulation of J-receptors in alveolar walls → reflex rapid shallow breathing

Sign	Pathophysiological Basis
Displaced apex beat	LV dilatation → apex shifted laterally and inferiorly ^[8]
S3 gallop (third heart sound)	Rapid ventricular filling into a dilated, non-compliant ventricle during early diastole → sudden deceleration of blood → low-frequency sound. S3 is the hallmark of volume overload/ventricular dilatation ^[8]
S4 (fourth heart sound)	Atrial contraction against a stiff ventricle — more common in diastolic dysfunction
Mitral regurgitation (functional MR) murmur	LV dilatation → stretching of the mitral annulus → malcoaptation of mitral leaflets → regurgitant flow. This is "functional" because the valve is structurally normal — it's the ventricle that's too big ^[8]
Pericardial friction rub	If concurrent pericarditis (myopericarditis). Three-component, scratchy sound best heard at left sternal border with patient sitting forward
Elevated JVP ^[3]	If RV involvement → ↑RA pressure → transmitted backward to jugular veins
Basal lung crackles / crepitations	LHF → ↑pulmonary capillary hydrostatic pressure → fluid transudation into alveoli

When myocarditis is fulminant, you see features of forward failure (inadequate perfusion) and backward failure (congestion):

Forward failure ^[9]:

Pallor, peripheral cyanosis
Cold, clammy extremities
Delayed capillary refill ( > 2 seconds)
Oliguria ( < 0.5 mL/kg/hr)
Altered consciousness (confusion, drowsiness)

Backward failure ^[9]:

Dyspnoea, wheeze, cough with pink frothy sputum
Cyanosis
Basal crackles
Displaced apex
Gallop rhythm (S3)

Etiology	Specific Sign
Hypersensitivity myocarditis	Acute rash, fever, peripheral eosinophilia ^[4]
Lyme disease	Erythema migrans (expanding target lesion), AV block
Chagas disease	Megacolon, megaesophagus (chronic phase)
Sarcoidosis	Bilateral hilar lymphadenopathy, erythema nodosum, uveitis
SLE	Malar rash, arthritis, serositis, oral ulcers
Diphtheria	Grey pharyngeal pseudomembrane, bull-neck swelling
Eosinophilic myocarditis	Associated with hypereosinophilia, sometimes with Löffler endocarditis (mural thrombi)

In neonates and infants, the presentation differs:

Age Group	Features
Neonates	Tachypnoea, poor feeding, irritability, pallor/mottling, hepatomegaly, sepsis-like picture. Often caused by enteroviral neonatal sepsis syndrome (transplacental or intrapartum Coxsackie B infection)
Infants	Poor feeding, failure to thrive, shortness of breath (especially on exertion/feeding), excessive sweating ^[10]. Compensatory tachycardia and cardiomegaly
Older children	More similar to adults: chest pain, palpitations, exercise intolerance, syncope

Clinical Pearl — The '40-Year-Old with Flu Then Heart Failure' Vignette

The classic exam vignette: A 40-year-old presents with a preceding flu-like illness who develops heart failure with displaced apex, S3 gallop, and mitral regurgitation from ventricular dilatation ^[8]. This is the "textbook" presentation of viral myocarditis → acute DCM-like picture. Diagnosis requires excluding coronary artery disease via catheterization, while endomyocardial biopsy remains the gold standard though carries perforation risk. Treatment is supportive with standard heart failure therapy ^[8].

The variability in presentation is explained by:

Amount of myocardium affected: Focal inflammation → subclinical; diffuse → fulminant
Location of inflammation: Conduction system → heart block; free wall → pump failure; subepicardial → pericarditis
Vigour of immune response: Brisk immune response → fulminant but may recover; smouldering → chronic DCM
Patient's baseline cardiac reserve: Young athlete → may tolerate ↓EF initially; elderly with comorbidities → decompensates early

High Yield Summary

Definition: Myocarditis = non-ischaemic inflammatory disease of myocardium. Inflammatory cardiomyopathy = myocarditis + cardiac dysfunction → can lead to DCM.

Epidemiology: Young adults (20–40), M > F. Major cause of sudden cardiac death in < 40y (~20%). In HK: viral causes predominate (Adenovirus, Echovirus, Coxsackie virus).

Pathophysiology — 3 Phases: (1) Direct viral myocyte injury → (2) Adaptive immunity + molecular mimicry → (3) Remodelling ± resolution vs DCM.

Classification: By course (acute / fulminant / chronic), by histology (Dallas: active / borderline), by pattern (lymphocytic / giant cell / eosinophilic / granulomatous), by clinical presentation (ACS-like / new-onset HF / life-threatening).

Clinical Features:

Prodrome: Viral flu-like illness weeks before cardiac symptoms
Symptoms: Chest pain (usually pericardial), dyspnoea, palpitations, syncope, fatigue
Signs: Tachycardia (out of proportion to fever), S3, displaced apex, functional MR, ↑JVP, lung crackles
Fulminant: Cardiogenic shock features (cold peripheries, ↓BP, oliguria, altered consciousness)

Key Pearls:

Chest pain in myocarditis = usually concomitant pericarditis
Tachycardia out of proportion to fever = myocarditis until proven otherwise
Avoid exertion → risk of fatal ventricular arrhythmias
DON'T give NSAIDs (↓PG → may worsen myocardial function + ↑necrosis)
EMB = gold standard but rarely done (1% perforation risk, usually doesn't change management)

Active Recall - Myocarditis (Definition to Clinical Features)

^[1] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf — Cardiovascular Diseases, Myocarditis section (p.423–425) ^[2] Senior notes: MBBS Final MB (Pediatrics) (Felix PY Lai).pdf — Cardiovascular Diseases, Myocarditis section (p.291) ^[3] Senior notes: Maksim Medicine Notes.pdf — Cardiology section 1.10, Myocarditis (p.40) ^[4] Senior notes: Ryan Ho Cardiology.pdf — Section 3.4.1 Myocarditis (p.165) ^[5] Lecture slides: Three Cases SOB 20211.pdf (p.29) — Etiology of Myocarditis ^[6] Senior notes: Ryan Ho Respiratory.pdf — COVID-19 Complications section (p.58) ^[7] Senior notes: Adrian Lui Pediatrics Notes.pdf — Acute Rheumatic Fever (p.235); Enterovirus infection (p.482) ^[8] Senior notes: learning_points_output.txt — Cardiology, Three Cases of Dyspnea (Learning Point 2) ^[9] Senior notes: Ryan Ho Critical Care.pdf — Management of Cardiogenic Shock (p.22) ^[10] Senior notes: Adrian Lui Pediatrics Notes.pdf — Approach to Pediatric Heart Failure (p.197)

Differential Diagnosis of Myocarditis

The differential diagnosis of myocarditis is challenging precisely because its presentation is so protean. As we discussed in the clinical features section, myocarditis can masquerade as three main clinical syndromes — ACS-like, new-onset heart failure, and life-threatening arrhythmia/shock. The differential therefore changes depending on which "face" the myocarditis is wearing. Let's work through this systematically from first principles.

The core problem: myocarditis produces a combination of chest pain + ↑troponin + ECG changes + ventricular dysfunction — and this combination is shared by many conditions. The troponin rise comes from myocyte necrosis (inflammation-mediated, not ischaemia-mediated), the ECG changes come from oedematous/inflamed myocardium distorting electrical conduction, and the ventricular dysfunction comes from impaired contractility. Each of these features individually overlaps with multiple other diagnoses.

Approach to the DDx — By Presenting Syndrome

The most practical way to think about the differential is to ask: "How did this patient present?" — and then consider the differential for that particular syndrome.

This is the most common diagnostic dilemma. A young patient with chest pain, troponin elevation, and ST-segment changes — is it MI or myocarditis?

Differential	Key Distinguishing Features	Why It Mimics Myocarditis
Acute coronary syndrome (ACS) / AMI	Typical cardiovascular risk factors (HTN, DM, smoking, hyperlipidaemia, family Hx); crescendo pattern; specific coronary territory on ECG (e.g. contiguous leads); regional wall motion abnormality (RWMA) matching a coronary territory on echo; coronary lesion on angiography	Both have chest pain, ↑cTn, ST/T changes, RWMA. Key differentiator: myocarditis has viral prodrome, younger age, no CVS risk factors, ECG changes not conforming to a single coronary territory, and coronary angiography is needed to rule out clinically significant CAD ^[8]^[11]
Acute pericarditis	Sharp, knife-like chest pain aggravated by respiratory movement; radiates to the trapezius ridge (characteristic site of pericardial pain) ^[12]; relieved by sitting forward; diffuse concave-up ST elevation with PR depression on ECG; pericardial friction rub	Often coexists (myopericarditis). Pure pericarditis has normal troponin and preserved LV function. If troponin rises or LV dysfunction appears → myocarditis component present
Takotsubo (stress) cardiomyopathy	Typically post-menopausal women after intense emotional/physical stress; apical ballooning with mid-basal hyperkinesis on echo; ↑cTn but disproportionately low relative to degree of wall motion abnormality; no obstructive CAD; resolves in days-weeks	Both have ↑cTn + ST changes + transient LV dysfunction without obstructive CAD. Takotsubo has characteristic circumferential apical pattern (not matching a coronary territory), and recovery is faster
Pulmonary embolism	Haemoptysis ^[12]; pleuritic chest pain; tachycardia + tachypnoea; ↑D-dimer; RV strain on echo/ECG (S1Q3T3, RV dilatation); CTPA confirms diagnosis; risk factors: immobilisation, surgery, malignancy, OCP	PE can cause ↑cTn (RV strain-mediated) and ST/T changes. But PE has RV > LV dysfunction and a thrombotic source
Aortic dissection	Radiation to back, ripping or tearing sensation ^[12]; sudden onset, maximal at onset; BP differential between arms; widened mediastinum on CXR; confirmed by CTA	Type A dissection can occlude coronary ostia → STEMI mimic + ↑cTn. Must be excluded before anticoagulation for ACS

GC High Yield — Differential Diagnosis of Acute Chest Pain

From GC 088 (Sudden Severe Chest Pain): The key differentials of acute chest pain include ^[12]:

Acute pericarditis — aggravated by respiratory movement, sharp, knife-like; radiates to the trapezius ridge
Pulmonary embolism — haemoptysis
Aortic dissection — radiation to back, ripping or tearing sensation

From GC 028 (Accelerating Chest Pain): Myocarditis and pericarditis are specifically listed as differentials of ACS ^[13].

These are must-know differentials for the in-house written paper.

When myocarditis presents as unexplained new heart failure — especially in a young patient — the differential includes all causes of dilated cardiomyopathy (DCM) and acute heart failure.

Differential	Key Distinguishing Features	Why It Mimics Myocarditis
Idiopathic / familial DCM	Family history of cardiomyopathy or sudden death; insidious onset (months-years); no viral prodrome; genetic testing may reveal laminopathy or other sarcomeric mutation	Both show LV dilatation + ↓LVEF + functional MR. Diagnosis of viral myocarditis presenting as DCM requires excluding coronary artery disease via catheterization ^[8]. Family history and genetic testing differentiate familial DCM
Ischaemic cardiomyopathy	Older patient; CVS risk factors; prior angina/MI history; regional (not global) wall motion abnormalities matching coronary territories; significant CAD on angiography	In older patients, always rule out ischaemic cause first. Myocarditis tends to cause global (diffuse) dysfunction, while ischaemic cardiomyopathy causes segmental dysfunction
Tachycardia-mediated cardiomyopathy	History of sustained tachycardia (often AF with rapid ventricular rate, or incessant SVT); rate-control/rhythm-control → LV function recovers	Uncontrolled tachycardia itself causes LV dysfunction. The key is that treating the arrhythmia restores function — in myocarditis, the arrhythmia is a consequence, not the cause
Peripartum cardiomyopathy	DCM presenting in the last month of pregnancy or within 5 months postpartum; no other identifiable cause; ↓LVEF	Age group and timing are diagnostic clues. Some peripartum cardiomyopathy may actually be triggered by viral myocarditis
Alcoholic cardiomyopathy	Heavy alcohol use history ( > 80g/day for > 5 years); reversible with abstinence	Toxic mechanism (mitochondrial damage + thiamine deficiency). History of alcohol use is the key differentiator
Chemotherapy-related cardiomyopathy	History of anthracycline (doxorubicin) or trastuzumab exposure; dose-dependent (anthracycline) or dose-independent (trastuzumab)	Known temporal relationship to drug exposure. Unlike myocarditis, there's no viral prodrome and cardiac MRI shows different patterns
Valvular heart disease (severe MR, AR)	Characteristic murmur on auscultation; echo shows structural valve pathology (not just functional regurgitation from ventricular dilatation)	Severe chronic MR/AR → volume overload → LV dilatation → HF. In myocarditis, the MR is functional (secondary to LV dilatation), not primary
Hypertensive heart disease	Long history of poorly controlled hypertension; LVH on echo/ECG; diastolic dysfunction predominates initially	Chronic pressure overload → hypertrophy → eventual systolic failure. Distinguished by HTN history and LVH pattern

Key Teaching Point — The 40-Year-Old Vignette

The classic exam scenario: a 40-year-old with preceding flu-like illness who develops heart failure with displaced apex, S3 gallop, and mitral regurgitation from ventricular dilatation → viral myocarditis presenting as dilated cardiomyopathy. Diagnosis requires excluding coronary artery disease via catheterization ^[8]. If there's no obstructive CAD and cardiac MRI shows inflammatory patterns → myocarditis is the diagnosis.

Differential	Key Distinguishing Features	Why It Mimics Myocarditis
Primary ventricular arrhythmia (idiopathic VT, Brugada, Long QT, ARVC)	Family history of sudden death; characteristic ECG patterns (Type 1 Brugada, prolonged QTc, epsilon waves in ARVC); no prodrome; structurally normal heart (except ARVC)	Both can present with VT/VF and sudden death. Inherited arrhythmia syndromes lack the inflammatory prodrome and have characteristic baseline ECG findings
Arrhythmogenic RV cardiomyopathy (ARVC)	Fibrofatty replacement of RV myocardium; epsilon waves on ECG; RV dilatation with RWMA; family history; diagnosed by Task Force criteria	Both can cause VT and RV dysfunction. ARVC has fibrofatty replacement (not inflammation) on MRI and a familial pattern
Cardiogenic shock from acute MI ^[9]	CVS risk factors; regional RWMA on echo; culprit lesion on angiography; ST elevation in contiguous leads	Both can present with cardiogenic shock. Cardiogenic shock causes: cardiomyopathic (MI, ADHF from DCMP, myocarditis, drug-induced), arrhythmogenic, mechanical ^[9]
Acute/fulminant myocarditis vs septic shock	In septic shock: warm peripheries (initially), ↓SVR, identifiable source of infection, positive cultures, ↑lactate; in myocarditis: cold peripheries (cardiogenic), ↑filling pressures, global LV dysfunction	Both present with shock and multiorgan dysfunction. Echo is the key differentiator — cardiogenic shock shows LV dysfunction + ↑filling pressures; septic shock shows hyperdynamic LV + ↓SVR

The DDx shifts significantly by age, as different causes of heart failure predominate at different developmental stages ^[10]^[14]:

Age Group	DDx for Myocarditis-like Presentation	Key Differentiators
Neonatal ( < 1 month)	Duct-dependent CHD (CoA, HLHS, critical AS, IAA); transient myocardial ischaemia from birth asphyxia; sepsis; hypoglycaemia/hypocalcaemia; congenital heart block; SVT	Duct-dependent lesions present with shock on duct closure (day 3–7). Sepsis has positive cultures + warm shock. SVT has narrow complex tachycardia > 220 bpm
Infant (2–3 months)	Large L-to-R shunts (VSD, AVSD, PDA); Kawasaki disease; anomalous left coronary artery from pulmonary artery (ALCAPA)	L-to-R shunts present with tachypnoea, hepatomegaly, FTT — murmur usually present. ALCAPA mimics MI (anterolateral ST changes + ↓LV function)
Older children/adolescents	Acute rheumatic fever; cardiomyopathy (iron overload, post-chemo, neuromuscular); infective endocarditis	ARF has Jones criteria features (migratory polyarthritis, chorea, erythema marginatum). Endocarditis has persistent fever + new murmur + embolic phenomena

Overlapping Feature	Differential Diagnoses	How to Differentiate from Myocarditis
Chest pain + ↑cTn	ACS/AMI, pericarditis, PE, aortic dissection, Takotsubo	Angiography (CAD?), CTPA (PE?), CTA (dissection?), echo pattern (Takotsubo?)
↑cTn without obstructive CAD	Myocarditis, Takotsubo, PE with RV strain, type 2 MI (demand ischaemia), hypertensive emergency, tachyarrhythmia, renal failure	Cardiac MRI (inflammatory oedema + LGE pattern in myocarditis)
New LV dysfunction	DCM (any cause), ischaemic cardiomyopathy, valvular disease, hypertensive HD, peripartum CMP	History, echo (global vs regional, valve structure), angiography
ECG mimicking MI	Myocarditis, pericarditis, Brugada, LVH, early repolarisation, hyperkalaemia	ECG findings in myocarditis may mimic AMI or pericarditis ^[11]; cardiac MRI is the key non-invasive differentiator
Ventricular arrhythmia in a young person	Myocarditis, ARVC, HCM, Brugada, Long QT, CPVT, idiopathic VT	Family history, baseline ECG, cardiac MRI, genetic testing

Feature	Myocarditis	ACS/AMI	Pericarditis	Takotsubo	PE
Age	Young (20–40)	Older (> 50 typically)	Any age	Post-menopausal F	Any age
Prodrome	Viral flu-like illness ^[4]	None (or chronic stable angina)	Viral illness possible	Emotional/physical stress	None
Chest pain character	Variable; pleuritic if pericardial component	Crushing, heavy, constricting	Sharp, positional, ↑inspiration ^[12]	ACS-like	Pleuritic
ECG	Non-specific ST/T; may mimic MI or pericarditis	Contiguous ST elevation or depression	Diffuse concave-up STE + PR depression	ST elevation (anterior leads)	S1Q3T3, RV strain
Troponin	↑ (variable, up to 1/3 normal ^[11])	↑↑ (proportional to infarct size)	Normal (or mildly ↑ if myopericarditis)	↑ (disproportionately low vs WMA)	↑ (if RV strain)
Echo	Global or diffuse ↓LVEF ± functional MR	Regional WMA matching coronary territory	Normal LV ± pericardial effusion	Apical ballooning, basal hyperkinesis	RV dilatation, D-shaped septum
Coronary angiography	Normal (no obstructive CAD)	Culprit lesion present	Normal	Normal	Normal
Cardiac MRI	Myocardial oedema + LGE in non-coronary distribution (typically subepicardial/mid-wall)	Subendocardial or transmural LGE matching coronary territory	Pericardial enhancement/effusion	Oedema without LGE (or minimal)	RV changes

Critical DDx Point

The single most important differential to exclude is ACS/AMI — because the management is completely different (antiplatelets + anticoagulation + reperfusion for ACS vs supportive care + activity restriction + avoid NSAIDs for myocarditis). Coronary angiography (or CT coronary angiogram) to rule out clinically significant CAD is therefore essential in any patient with chest pain + ↑troponin where myocarditis is suspected ^[3]^[8]^[11].

Special Differentials Worth Knowing for Exams

Both cause conduction defects (especially AV block), ventricular arrhythmias, and LV dysfunction. Sarcoidosis has non-caseating granulomas on biopsy, often with bilateral hilar lymphadenopathy on CXR, ↑ACE levels, and characteristic MRI pattern (patchy mid-wall or epicardial LGE, often basal septum). The conduction disease in sarcoidosis is often out of proportion to the degree of LV dysfunction.

Both are "myocarditis" but giant cell myocarditis is rapidly fatal without immunosuppression (median survival 5.5 months). Suspect if: new-onset HF of 2 weeks – 3 months with dilated LV and new ventricular arrhythmia, 2nd or 3rd degree heart block, or failure to respond to usual care within 1–2 weeks ^[1]^[2]. This is an indication for EMB.

When myocarditis is part of a systemic condition, the other system manifestations provide the diagnostic clue:

Systemic Disease	Clue to the Underlying Diagnosis
SLE	Malar rash, arthritis, serositis, anti-dsDNA, low complement
Rheumatic fever	Migratory polyarthritis, chorea, erythema marginatum, anti-streptolysin O
Lyme disease	Erythema migrans, tick exposure, endemic area, AV block
MCTD	Raynaud phenomenon, swollen fingers, anti-U1 RNP, pulmonary hypertension ^[15]
Eosinophilic myocarditis	Peripheral eosinophilia, drug/parasite exposure, rash
COVID-19 / MIS-A	Recent COVID infection (2–12 weeks prior), fever, ↓BP, rash, conjunctival injection, ↑inflammatory markers ^[6]

High Yield Summary — Differential Diagnosis of Myocarditis

The DDx depends on how myocarditis presents:

ACS-mimic → DDx: AMI, pericarditis, PE, aortic dissection, Takotsubo
- Key action: Coronary angiography/CT coronary angiogram to rule out CAD ^[8]^[11]
- Key differentiators: viral prodrome, young age, no CVS risk factors, non-coronary LGE on MRI
New-onset HF → DDx: All causes of DCM (idiopathic/familial, ischaemic, alcoholic, peripartum, tachycardia-mediated, chemotherapy-related, valvular)
- Key action: Exclude ischaemic cause with angiography; cardiac MRI for inflammatory pattern
Arrhythmia/SCD → DDx: Inherited arrhythmia syndromes (Brugada, Long QT, ARVC, HCM), primary VT
- Key differentiators: Family history, baseline ECG patterns, fibrofatty replacement vs inflammation on MRI
Paediatric HF → DDx varies by age: neonatal (duct-dependent CHD, sepsis), infant (L-to-R shunts, ALCAPA), older child (ARF, cardiomyopathy, IE)

Remember: ECG in myocarditis may mimic AMI or pericarditis ^[11]^[14] — this is a classic exam pitfall. The endomyocardial biopsy is the gold standard ^[11] but is rarely done; cardiac MRI is the key non-invasive differentiator.

Active Recall - Differential Diagnosis of Myocarditis

References

^[1] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf — Cardiovascular Diseases, Myocarditis, Diagnosis section (p.425) ^[2] Senior notes: MBBS Final MB (Pediatrics) (Felix PY Lai).pdf — Cardiovascular Diseases, Myocarditis, Diagnosis section (p.293–294) ^[3] Senior notes: Maksim Medicine Notes.pdf — Cardiology section 1.10, Myocarditis (p.40) ^[4] Senior notes: Ryan Ho Cardiology.pdf — Section 3.4.1 Myocarditis (p.165) ^[6] Senior notes: Ryan Ho Respiratory.pdf — COVID-19 Complications section (p.58) ^[8] Senior notes: learning_points_output.txt — Cardiology, Three Cases of Dyspnea (Learning Point 2) ^[9] Senior notes: Ryan Ho Critical Care.pdf — Management of Cardiogenic Shock (p.22) ^[10] Senior notes: Adrian Lui Pediatrics Notes.pdf — Approach to Pediatric Heart Failure (p.197) ^[11] Lecture slides: Three Cases SOB 20211.pdf — Myocarditis Diagnosis (p.25, 27, 32) ^[12] Lecture slides: GC 088. Sudden Severe Chest Pain.pdf — Differential diagnosis (p.13) ^[13] Lecture slides: GC 028. Accelerating chest pain_Acute coronary.pdf — Differential Diagnosis of ACS (p.16–17) ^[14] Senior notes: MBBS Final MB (Pediatrics) (Felix PY Lai).pdf — Causes of heart failure in children and infants (p.204) ^[15] Senior notes: Ryan Ho Rheumatology.pdf — MCTD, Prognosis (p.87)

Diagnostic Criteria, Algorithm, and Investigations for Myocarditis

Before diving into the criteria and investigations, it's worth understanding why myocarditis is one of the hardest cardiac diagnoses to make:

No single pathognomonic test: Unlike AMI (troponin + contiguous ST changes + culprit lesion on angiography), myocarditis has no single test that clinches the diagnosis.
Clinical features are non-specific: Chest pain, troponin rise, ECG changes, and LV dysfunction all overlap with ACS, pericarditis, Takotsubo, and cardiomyopathies.
Investigations have limitations: Troponin can be normal (up to 1/3 normal! ^[11]); ECG is non-diagnostic; echo is non-specific; even the gold standard (EMB) has sampling error.
The diagnosis is therefore made by putting together a clinical picture — prodrome + cardiac features + investigations — and excluding mimics (especially CAD).

Diagnostic Criteria

Unlike many conditions, there is no universally accepted single set of "diagnostic criteria" for myocarditis in the way there is for MI or rheumatic fever. Instead, the diagnosis relies on clinical suspicion → non-invasive testing → ± invasive confirmation. The key frameworks are:

Clinically suspected myocarditis requires ≥1 clinical presentation + ≥1 diagnostic criterion from investigations, in the absence of obstructive CAD and other conditions that could explain the presentation.

Clinical presentations (at least one):

Acute chest pain (pericarditic or pseudo-ischaemic)
New-onset (days to 3 months) or worsening dyspnoea at rest or on exertion ± signs of LHF/RHF
Subacute/chronic (> 3 months) dyspnoea ± signs of LHF/RHF
Palpitations ± arrhythmia symptoms ± syncope ± aborted SCD
Unexplained cardiogenic shock

Diagnostic criteria from investigations (at least one):

ECG/Holter/stress test abnormalities (new ST/T changes, AV block, arrhythmias)
Elevated myocardial biomarkers (cTnT/cTnI, CK-MB)
Functional/structural abnormalities on echo or CMR (new or unexplained LV/RV dysfunction, regional/global wall motion abnormalities)
CMR tissue characterisation consistent with myocarditis (Lake Louise criteria — see below)

Plus: exclusion of obstructive CAD (by angiography or CT coronary angiogram), valvular disease, and other known causes that could fully account for the presentation.

Key Concept — The Diagnosis is One of Exclusion + Inclusion

You must include evidence of myocardial inflammation (clinical + investigations) AND exclude conditions that could explain the same picture — especially coronary artery disease. This is why CT coronary angiogram / cardiac catheterization to rule out clinically significant CAD ^[11] is an essential part of the diagnostic workup.

The Dallas criteria are the histological standard applied to endomyocardial biopsy (EMB) specimens ^[1]^[2]^[4]:

Category	Definition	What It Means
Active myocarditis	Evidence of inflammatory infiltrate of the myocardium + infiltrates associated with myocyte necrosis or degeneration of adjacent myocytes not typical of the ischaemic damage associated with coronary artery disease ^[1]^[2]	This is the definitive histological diagnosis. The qualifier "not typical of ischaemic damage" is crucial — it means the necrosis pattern is patchy/multifocal (inflammation-driven), not following a coronary territory (ischaemia-driven)
Borderline myocarditis	Inflammatory infiltrate present but without myocyte necrosis	Inflammation is there but hasn't progressed to cell death. May represent early or resolving disease, or sampling error
No myocarditis	No inflammatory infiltrate	Negative biopsy — but doesn't exclude myocarditis (sampling error from patchy disease)

On follow-up biopsy (if performed):

Ongoing/persistent: continued active or borderline myocarditis
Resolving/healing: reduction in inflammatory infiltrate ± fibrosis
Resolved/healed: no inflammatory infiltrate; interstitial fibrosis may remain

The Dallas criteria alone have poor sensitivity (sampling error) and poor inter-observer agreement. The immunohistochemical criteria provide a more objective quantification ^[1]^[2]:

Abnormal inflammatory infiltrate defined as ≥ 14 leucocytes/mm² including up to 4 monocytes/mm² with presence of CD3-positive T-lymphocytes ≥ 7 cells/mm² ^[1]^[2]
Myocarditis can be classified based on the type of inflammatory cell infiltrate: lymphocytic, eosinophilic, polymorphic, and giant cell myocarditis ^[1]^[2]

Why IHC matters: it uses specific antibodies (anti-CD3 for T cells, anti-CD68 for macrophages) to precisely identify and count inflammatory cells, reducing inter-observer variability and improving sensitivity over H&E-stained Dallas criteria alone.

The Lake Louise criteria are the non-invasive diagnostic standard for myocarditis on cardiac MRI. The 2018 update introduced parametric mapping (T1 and T2 mapping) alongside the original criteria, significantly improving diagnostic accuracy.

Diagnosis requires at least one criterion from each of two categories:

Category	Criterion	What It Detects	Pathophysiological Basis
T2-based criteria (oedema markers) — at least one:	↑T2 signal intensity (regional or global)	Inflammatory oedema ^[1]^[2]^[16]	Inflammation → capillary leak → interstitial oedema → ↑free water content → ↑T2 signal (T2 is sensitive to water content)
	↑T2 mapping values (global or regional)	Myocardial oedema	Same principle but quantitative — removes subjectivity
T1-based criteria (injury/fibrosis markers) — at least one:	↑Early gadolinium enhancement (EGE) relative to skeletal muscle	Inflammatory hyperaemia ^[1]^[2]^[16]	Inflammation → vasodilatation + ↑capillary permeability → gadolinium leaks into interstitium faster → ↑signal on early post-contrast images
	Late gadolinium enhancement (LGE) in non-ischaemic distribution	Necrosis or scar ^[1]^[2]^[16]	Necrotic/fibrotic myocardium has expanded extracellular space → gadolinium accumulates and washes out slowly → bright signal on late imaging (10–15 min post-contrast)
	↑Native T1 mapping values or ↑extracellular volume (ECV)	Diffuse oedema/fibrosis	Native T1 increases with both oedema and fibrosis; ECV maps extracellular space expansion

Supportive criteria:

Changes in ventricular size and geometry ^[1]^[2]^[16]
Regional or global wall motion abnormalities ^[1]^[2]^[16]
Pericardial effusion

High Yield — LGE Distribution Pattern Differentiates Myocarditis from MI

The distribution of LGE on cardiac MRI is the single most important feature for differentiating myocarditis from MI:

Myocarditis: LGE is typically subepicardial (starting from the outer layer) or mid-wall (within the middle of the myocardium), in a non-coronary distribution (i.e., not matching a single coronary artery territory). This is because viral entry and inflammation tend to start at the epicardium (which has the most lymphatic drainage) and work inward.
MI: LGE is subendocardial (starting from the inner layer) or transmural, matching a specific coronary territory. This is because ischaemia starts at the subendocardium (furthest from blood supply, highest metabolic demand) and extends outward ("wavefront of necrosis").
Patchy mid-wall late gadolinium enhancement suggests myocarditis ^[16]
Dyskinesia with late gadolinium enhancement at anterobasal septum suggests cardiac sarcoidosis ^[16]

Feature	Dallas Criteria	IHC Criteria	Lake Louise Criteria
Modality	EMB histology (H&E stain)	EMB with immunostaining	Cardiac MRI
Invasiveness	Invasive (EMB)	Invasive (EMB)	Non-invasive
Sensitivity	Low (~50%) due to sampling error + patchy disease	Higher (~70%) — quantitative cell counting	~80% (improved with 2018 update)
Specificity	High (if positive)	High	Moderate-high (~75%)
Key advantage	Definitive when positive; classifies histological subtype	Objective quantification; classifies cell types	Non-invasive; widely available; can be repeated
Key limitation	Sampling error; inter-observer variability	Still requires EMB; sampling error	Cannot classify histological subtype; contraindicated with certain devices

The following algorithm represents the practical approach to diagnosing myocarditis, integrating the ESC position statement framework with the key investigations.

GC High Yield — The Diagnostic Approach from Lecture Slides

From the Three Cases of Dyspnea lecture ^[11]:

Diagnosis of myocarditis requires:

History: recent flu-like syndrome accompanied by fever, arthralgia, and malaise
Laboratory tests: leukocytosis, high ESR, elevated cardiac enzyme
ECG: Ventricular arrhythmias or heart block, or mimic AMI or pericarditis
Autoimmune marker / Viral serology
Echocardiogram / MRI
CT coronary angiogram / cardiac catheterization: to R/O clinically significant CAD
Endomyocardial biopsy: gold standard for the diagnosis of myocarditis but associated risk of cardiac perforation (1%) and no proven histological guided therapy — except giant cell myocarditis

Note the lecture slide specifically states that troponin can be up to 1/3 normal! ^[11] — this is a high-yield exam point.

Investigation Modalities — Detailed Breakdown

1. Blood Tests

Test	Expected Finding	Why	Interpretation
ESR	↑ ^[1]^[2]^[4]^[11]	Acute phase reactant; reflects systemic inflammation (↑fibrinogen → ↑rouleaux formation → ↑sedimentation)	Non-specific; elevated in any inflammatory or infectious process
CRP	↑ ^[1]^[2]^[4]^[11]	Synthesised by hepatocytes in response to IL-6; rises within 6 hours of inflammation	More specific to acute inflammation than ESR; useful for monitoring
CBC	Leukocytosis ^[11]	Bone marrow response to infection/inflammation → ↑WBC production	Non-specific. Look for eosinophilia (suggests eosinophilic myocarditis or hypersensitivity)

Test	Expected Finding	Why	Key Caveats
Cardiac troponin (cTnI/cTnT)	↑ ^[1]^[2]^[3]^[4]^[11]	Myocyte necrosis → troponin (a structural protein of the contractile apparatus) leaks from damaged cells into the bloodstream	Cardiac biomarkers elevation reflects myocardial necrosis which is seen in some but not all patients with myocarditis. Elevated markers suggest the diagnosis but absence of elevation does not rule out its diagnosis ^[1]^[2]. Up to 1/3 may be normal ^[11]. Rise and fall pattern in myocarditis: peak at ~1 day, elevated for ~7 days (cf. AMI: peak at 24–48h, return to baseline over 5–14 days) ^[17]
CK-MB	↑	CK-MB is the cardiac-specific isoenzyme of creatine kinase. Released from damaged myocytes	Less sensitive and less specific than troponin. Useful historically; shorter half-life makes it better for detecting reinfarction
High-sensitivity troponin (hsTnT/hsTnI)	Any value > 99th percentile URL is abnormal	hsTn assays detect much smaller amounts of troponin. hsTnT diagnostic cutoff: positive if baseline > 14 ng/L and > 100% rise 3–6h later ^[17]	hsTn can be elevated in many non-ACS conditions: HF, CKD, PE, Takotsubo, myocarditis, sepsis — hence the term "troponin-positive" is not synonymous with MI

Test	Expected Finding	Why	Interpretation
BNP / NT-proBNP	↑ if HF present ^[1]^[2]	BNP = Brain Natriuretic Peptide (misnomer — actually released primarily from ventricular cardiomyocytes in response to volume overload/wall stress). "B" originally stood for "brain" because it was first isolated from porcine brain tissue. NT-proBNP is the inactive N-terminal fragment cleaved from proBNP	BNP > 400 pg/mL suggestive of HF; BNP < 100 pg/mL has strong negative predictive value for HF ^[1]^[2]. NT-proBNP: age < 50: > 450 pg/mL for HF; age 50–75: > 900 pg/mL; age > 75: > 1800 pg/mL ^[1]^[2]. Indicated when HF is suspected but diagnosis is uncertain — helps distinguish cardiac from non-cardiac dyspnoea

Why does the BNP cutoff change with age? Because healthy ageing → increased ventricular stiffness + mild renal impairment (↓clearance of NT-proBNP) → baseline levels are higher in the elderly.

Test	Purpose
Viral serology ^[4]^[11]	Paired acute and convalescent sera (IgM/IgG for Coxsackie, Adenovirus, EBV, CMV, HIV, HCV, Parvovirus B19). Rising titre (≥4-fold) supports recent viral infection. However, serology has low sensitivity and specificity for confirming viral myocarditis specifically
Autoimmune markers ^[4]^[11]	ANA, anti-dsDNA (SLE), RF/ACPA (RA), ANCA (GPA/EGPA), ACE level (sarcoidosis). Requested when autoimmune aetiology is suspected based on clinical picture
Toxicology screen	Cocaine, amphetamines — if drug-induced myocarditis suspected
Peripheral blood eosinophil count	If ↑ → consider eosinophilic myocarditis (hypersensitivity, parasitic, hypereosinophilic syndrome)

ECG is NOT diagnostic — it can be normal and shows non-specific abnormalities ^[1]^[2]^[16]. However, it is the first-line test obtained in all patients with cardiac symptoms and provides important clues.

ECG Finding	Frequency	Pathophysiological Basis	DDx Pitfall
Non-specific ST-T wave changes ^[1]^[2]^[3]^[4]	Most common	Myocardial oedema + inflammation → altered repolarisation	Can mimic ischaemia or pericarditis
Ventricular arrhythmias (VT/VF) ^[1]^[2]^[4]^[11]	Variable	Inflammation → electrical heterogeneity → re-entry circuits	May be the presenting feature; can cause SCD
Heart block (1st, 2nd, 3rd degree AV block) ^[1]^[2]^[4]^[11]	Suggests specific aetiologies	Inflammation of conduction tissue (AV node, His bundle). Particularly seen in Lyme disease, sarcoidosis, giant cell myocarditis	New AV block in a young person without structural HD = think myocarditis or sarcoidosis
Atrial arrhythmias (AF, atrial ectopics) ^[1]^[2]	Variable	Atrial inflammation/dilatation → altered atrial electrophysiology	May coexist with ventricular arrhythmias
Abnormal Q waves ^[1]^[2]	Uncommon	Extensive myocyte necrosis mimicking transmural infarction	May mimic AMI ^[1]^[2]^[11] — but Q waves in myocarditis don't follow a coronary territory
QRS widening ^[1]^[2]	Uncommon	Slowed conduction through oedematous/fibrotic myocardium	New LBBB in myocarditis is an ominous sign
Sinus tachycardia	Very common	Compensatory SNS activation from ↓CO + fever	"Tachycardia out of proportion to fever" — clinical pearl
Diffuse ST elevation with PR depression	If pericarditis component	Pericardial inflammation → current of injury	Mimics pericarditis; suggests myopericarditis
Low voltage QRS	If pericardial effusion	Fluid surrounding heart attenuates electrical signal	Consider tamponade if combined with hypotension

ECG Mimicry — An Exam Favourite

ECG findings in myocarditis may mimic acute pericarditis or AMI ^[1]^[2]^[11]. This is one of the most commonly examined concepts. The key teaching point: if a young patient with a viral prodrome has ST elevation, always consider myocarditis/pericarditis before ACS. The ST elevation in pericarditis is diffuse and concave-up with PR depression; in MI it is convex-up in contiguous leads with reciprocal depression.

Finding	What It Tells You	Pathophysiological Basis
Cardiomegaly ^[1]^[2]^[3]	Ventricular dilatation	Inflammation → ↓contractility → Frank-Starling compensation → ventricular dilatation. CTR > 0.5 on PA film
Pulmonary congestion ^[1]^[2]^[3]	Left heart failure	↑LVEDP → ↑pulmonary capillary pressure → transudation. CXR findings correlate with left atrial pressure: upper lobe diversion at 10–15 mmHg, Kerley B lines at 15–20 mmHg, and alveolar oedema above 25 mmHg ^[8]
Pleural effusion	Severe HF or pericardial involvement	Bilateral transudative effusions from ↑hydrostatic pressure
Normal CXR	Does not exclude myocarditis	Early or mild myocarditis may have normal cardiac size and no congestion

Echocardiography is indicated to detect impaired ventricular function and left ventricular dilatation ^[1]^[2]. It is the first-line imaging modality because it is bedside, non-invasive, and rapidly available.

Echo Finding	Significance	Pathophysiological Basis
↓LVEF (global or regional)	Myocardial dysfunction	Diffuse myocyte damage → ↓contractility → ↓EF. May be global (typical of myocarditis) or regional (can mimic MI — but pattern doesn't match a coronary territory)
LV dilatation	Volume overload / remodelling	Acute: myocardial oedema → swelling. Chronic: compensatory dilatation
Regional or global wall motion abnormalities ^[1]^[2]^[16]	Active inflammation or necrosis	Inflamed/necrotic segments contract poorly → hypokinesis, akinesis, or dyskinesis
Functional MR or TR ^[1]^[2]	Secondary to ventricular dilatation	Annular dilatation → malcoaptation of valve leaflets. The valve itself is structurally normal
Pericardial effusion ^[1]^[2]	Concomitant pericarditis	Myopericarditis → pericardial inflammation → exudative effusion
Increased wall thickness	Myocardial oedema (acute)	Interstitial oedema → ↑wall thickness (unlike chronic DCM where wall is thin). This can be a clue to acute vs chronic disease
Diastolic dysfunction	Stiff, oedematous myocardium	Oedema + inflammatory infiltrate → ↓compliance → impaired relaxation

Echo Tip — Acute Myocarditis vs Chronic DCM

In acute myocarditis, the LV may appear normal-sized or mildly dilated with increased wall thickness (oedema), whereas in chronic DCM, the LV is dilated with thinned walls. This distinction helps gauge the acuity of the process.

Cardiac MRI enables detection of features of myocarditis ^[1]^[2] and is considered the best non-invasive test for confirming the diagnosis. The Updated Lake Louise Criteria (2018) are applied.

CMR Sequence / Technique	What It Detects	Finding in Myocarditis	Pathophysiological Basis
T2-weighted imaging / T2 mapping	Myocardial oedema	↑T2 signal intensity consistent with inflammatory oedema ^[1]^[2]	Inflammation → capillary leak → ↑interstitial water → ↑T2 relaxation time
Early gadolinium enhancement (EGE)	Hyperaemia/capillary leak	↑Early myocardial contrast enhancement relative to skeletal muscles consistent with inflammatory hyperaemia ^[1]^[2]	Vasodilatation + ↑capillary permeability → gadolinium leaks into myocardial interstitium faster than into skeletal muscle
Late gadolinium enhancement (LGE)	Necrosis or fibrosis/scar	Presence of LGE consistent with necrosis or scar ^[1]^[2] — subepicardial or mid-wall, non-coronary distribution	Necrotic/fibrotic tissue has expanded extracellular space → gadolinium accumulates and washes out slowly → bright signal at 10–15 min post-contrast
Native T1 mapping	Diffuse oedema/fibrosis	↑Native T1 values	T1 increases with both oedema (acute) and fibrosis (chronic). Advantage: quantitative + no contrast needed
Extracellular volume (ECV) mapping	Extracellular space expansion	↑ECV fraction	Calculated from pre/post-contrast T1 values + haematocrit. ↑ECV reflects oedema or fibrosis
Cine imaging	Ventricular function	Changes in ventricular size and geometry; regional or global wall motion abnormalities ^[1]^[2]	Functional assessment — same as echo but with superior spatial resolution

How to interpret the LGE pattern — the most discriminating feature:

LGE Pattern	Diagnosis	Why
Subepicardial / mid-wall, patchy, non-coronary territory	Myocarditis	Inflammation starts at epicardium → works inward; not limited by coronary supply
Subendocardial → transmural, coronary territory	Myocardial infarction	Ischaemic wavefront starts at subendocardium (highest O₂ demand, furthest from supply)
Basal septum, mid-wall	Cardiac sarcoidosis	Granulomas preferentially affect the basal septum and conduction tissue ^[16]
Diffuse subendocardial (circumferential)	Amyloidosis	Diffuse infiltration of extracellular space by amyloid fibrils
None or minimal	Takotsubo	Oedema without significant necrosis (reversible stunning)

CT coronary angiogram / cardiac catheterization: to R/O clinically significant CAD ^[3]^[8]^[11]

Modality	When to Use	What to Look For
CT coronary angiogram (CTCA)	Haemodynamically stable patients with low-intermediate pre-test probability of CAD; first-line in younger patients	Absence of obstructive coronary disease (typically < 50% stenosis) confirms non-ischaemic aetiology
Invasive coronary angiography (ICA)	Haemodynamically unstable; high pre-test probability; if CTCA inconclusive; can also be combined with EMB	Gold standard for coronary anatomy. Normal coronaries + clinical picture → supports myocarditis

Why is this step essential? Diagnosis of viral myocarditis presenting as dilated cardiomyopathy requires excluding coronary artery disease via catheterization ^[8]. You cannot diagnose myocarditis without first ruling out the most common cause of troponin elevation + LV dysfunction — which is ischaemic heart disease.

7. Endomyocardial Biopsy (EMB) — The Gold Standard

Endomyocardial biopsy is the gold standard for the diagnosis of myocarditis ^[1]^[2]^[4]^[11].

Approach: Usually via right internal jugular vein or femoral vein → right ventricle → bioptome samples from the RV septal surface (less commonly LV via arterial approach)
Samples: Typically 5–7 samples taken from the interventricular septum (avoiding the thin-walled free wall → perforation risk)

Routine biopsy is NOT indicated in most cases ^[1]^[2]. It is reserved for specific scenarios where it will change management ^[4]:

Scenario	Suspected Condition	Why EMB Changes Management
New-onset HF < 2 weeks with normal size or dilated LV and haemodynamic compromise ^[1]^[2]	Suspected fulminant lymphocytic myocarditis	Confirms inflammatory aetiology; if giant cell or eosinophilic → immunosuppression; if viral → supportive only
New-onset HF of 2 weeks – 3 months with dilated LV and new ventricular arrhythmia, 2nd or 3rd degree heart block, or failure to respond to usual care within 1–2 weeks ^[1]^[2]	Suspected giant cell myocarditis	Giant cell myocarditis requires aggressive immunosuppression (steroids + cyclosporine/azathioprine) and often transplant evaluation. Without treatment, median survival is 5.5 months
Unexplained restrictive cardiomyopathy	Infiltrative disease (amyloid, sarcoid)	Histology identifies specific infiltrate → targeted therapy
Suspected cardiac tumour	Lymphoma, metastatic disease	Histology guides oncological management

Analysis	Method	Finding	Significance
H&E histology	Dallas criteria	Inflammatory infiltrate ± myocyte necrosis	Confirms active myocarditis
Immunohistochemistry	Anti-CD3 (T cells), anti-CD68 (macrophages), anti-CD20 (B cells)	≥14 leucocytes/mm² with CD3+ T cells ≥7/mm²	More sensitive than Dallas criteria; classifies cell type
PCR for microbial pathogens	Viral genome detection (enterovirus, adenovirus, parvovirus B19, HHV-6, etc.)	Positive in up to one-third of cases ^[11]	Identifies viral aetiology; if PCR positive → no immunosuppression (virus still present). If PCR negative → consider immunosuppression
Immunoglobulin staining	IgM, IgG, IgA binding	Immunoglobulin binding to sarcolemma and fibrils	Fulminant: IgM predominance (early immune response). Chronic: IgG predominance (mature immune response) ^[11]

Associated risk of cardiac perforation (1%) ^[4]^[11]
Sampling error: Myocarditis is often patchy/focal → biopsy may miss the affected area (false negative rate ~50% with a single biopsy; improves with multiple samples and IHC)
No proven histological guided therapy — except giant cell myocarditis ^[11]
Low sensitivity when < 5 samples taken

EMB — When It Matters and When It Doesn't

A common exam mistake is to say "EMB should be done in all suspected myocarditis." It should not. EMB is reserved for cases where the result will change management:

Will change management: Fulminant/rapidly deteriorating HF unresponsive to therapy (giant cell? → immunosuppression), eosinophilic myocarditis (remove trigger + steroids), cardiac sarcoidosis (steroids)
Won't change management: Typical viral myocarditis in a haemodynamically stable young patient with a clear viral prodrome and positive Lake Louise criteria on MRI → treat supportively regardless of biopsy result

Investigation	Purpose	When to Order
Holter monitoring	Detect paroxysmal arrhythmias (VT, AV block) that may be intermittent	All patients during acute phase; ongoing monitoring during recovery
Cardiac catheterisation with haemodynamic assessment	Measure filling pressures, cardiac output; differentiate cardiogenic from other shock	Fulminant myocarditis with cardiogenic shock
PET-CT (FDG-PET)	Detect active inflammation (↑FDG uptake in inflamed myocardium)	Suspected cardiac sarcoidosis (focal uptake in basal septum)
Genetic testing	Rule out inherited cardiomyopathy	Family history of cardiomyopathy or sudden death; persistent DCM phenotype after acute phase

Step	Investigation	Purpose	Key Findings
1	History + examination	Clinical suspicion	Viral prodrome → cardiac symptoms
2	ECG	Detect arrhythmia + ST/T changes	Non-specific; may mimic AMI or pericarditis
3	Bloods (cTn, CRP/ESR, BNP, CBC)	Confirm myocardial injury + inflammation + HF	↑cTn (but may be normal in 1/3), ↑inflammatory markers, ↑BNP if HF
4	CXR	Assess cardiac size + pulmonary congestion	Cardiomegaly ± pulmonary oedema
5	Echo	Assess ventricular function + structure	↓LVEF, RWMA, pericardial effusion, functional MR/TR
6	Rule out CAD	CTCA or invasive angiography	Normal coronaries
7	Cardiac MRI	Confirm myocarditis (Lake Louise criteria)	T2 oedema + subepicardial/mid-wall LGE
8	EMB (if indicated)	Definitive histological diagnosis	Dallas criteria + IHC + PCR

Active Recall - Diagnosis of Myocarditis

References

^[1] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf — Cardiovascular Diseases, Myocarditis, Diagnosis section (p.425–426) ^[2] Senior notes: MBBS Final MB (Pediatrics) (Felix PY Lai).pdf — Cardiovascular Diseases, Myocarditis, Diagnosis section (p.293–294) ^[3] Senior notes: Maksim Medicine Notes.pdf — Cardiology section 1.10, Myocarditis (p.40) ^[4] Senior notes: Ryan Ho Cardiology.pdf — Section 3.4.1 Myocarditis (p.165) ^[8] Senior notes: learning_points_output.txt — Cardiology, Three Cases of Dyspnea (Learning Point 2) ^[11] Lecture slides: Three Cases SOB 20211.pdf — Myocarditis: Diagnosis (p.25, 27, 32) ^[16] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf — Dilated Cardiomyopathy, Cardiac MRI section (p.535) ^[17] Senior notes: Maksim Medicine Notes.pdf — Cardiology section 1.2, Cardiac enzymes and ACS biomarkers (p.6–9)

Management of Myocarditis

Before listing drugs and devices, you need to understand a fundamental truth about myocarditis management:

The myocardium has very limited regenerative capacity. Cardiomyocytes are terminally differentiated — they don't meaningfully proliferate after injury. So the goal of management is NOT to "fix" the damaged muscle; rather, it is to:

Support the heart while it heals (if it can) — treat the consequences (HF, arrhythmia)
Prevent further damage — avoid things that worsen myocyte death (NSAIDs, exercise, alcohol)
Treat the underlying cause if one is identified (rare) — immunosuppression for autoimmune/giant cell; remove offending drug; treat infection
Bridge to recovery or transplant — mechanical circulatory support in refractory cases

Management is usually supportive ^[4]. Supportive care is the first line of therapy for patients with myocarditis ^[11]. This is because for the most common form (viral/lymphocytic myocarditis), there is no proven specific treatment ^[4]^[11] — the inflammation is self-limiting in most cases, and immunosuppression for viral myocarditis may actually worsen outcomes by impairing viral clearance.

Treatment Modalities — In Detail

1. General Measures (All Patients)

These apply to every patient with myocarditis, regardless of severity or aetiology.

Avoid exertion → may induce potentially fatal ventricular arrhythmias ^[4]. No exercise for 3–6 months after myocarditis ^[18].

Recommendation	Duration	Rationale
No competitive sport	Minimum 3–6 months from onset	Inflamed myocardium is electrically unstable. Exercise → ↑catecholamines → ↑automaticity + ↑triggered activity in vulnerable tissue → VT/VF → sudden cardiac death. This is why myocarditis is a leading cause of SCD in young athletes
Leisure-time activities only if high risk for life-threatening arrhythmias ^[18]	Ongoing risk assessment	If LV function normalises, no arrhythmias on follow-up, and inflammation resolved on MRI → gradual return to activity
Return-to-play criteria (ESC/ACC)	After resolution	Requires: ≥3–6 months symptom-free; normal LVEF on echo; no significant arrhythmias on Holter/exercise testing; resolution of inflammation on repeat CMR (no oedema)

Why 3–6 months? This is the typical time for viral myocarditis to resolve through the three phases (viral entry → immune response → remodelling). Exercising during active inflammation is like pouring petrol on fire.

What to Avoid	Why	Mechanism
NSAIDs ^[1]^[2]^[4]	NSAIDs are proven NOT effective and may even enhance the myocarditic process and increase mortality in myocarditis (in contrast with pericarditis which may be useful) ^[1]^[2]	NSAIDs inhibit cyclooxygenase (COX) → ↓prostaglandin E₂ and I₂ production. Prostaglandins normally exert cardioprotective effects: vasodilatory, anti-inflammatory signalling, and ↓platelet aggregation. Blocking them in inflamed myocardium → ↑myocardial necrosis + sodium/water retention → ↑preload → worsen HF. Animal studies showed ↑viral replication and ↑mortality with NSAIDs in viral myocarditis
Heavy alcohol consumption ^[1]^[2]	Direct myocardial toxin	Alcohol damages mitochondria in cardiomyocytes → ↓ATP production → ↓contractility. Alcohol also depletes thiamine → wet beriberi → additional cardiomyopathy. Adding alcohol toxicity to inflamed myocardium = compounded injury
Exercise ^[1]^[2]^[3]^[4]^[18]	Risk of fatal arrhythmia	As above — electrical instability in inflamed myocardium + catecholamine surge from exercise = VT/VF risk
Non-DHP calcium channel blockers (verapamil, diltiazem)	Negative inotropic effect	In patients with reduced LVEF, the negative inotropic effect of verapamil/diltiazem can precipitate acute decompensation

High Yield — NSAIDs in Myocarditis vs Pericarditis

This is a classic exam trap. NSAIDs are FIRST-LINE for acute pericarditis (where they reduce pericardial inflammation effectively) but are CONTRAINDICATED in myocarditis (where they worsen myocardial necrosis and mortality). In myopericarditis (both components present), the decision depends on the dominant pathology — if significant LV dysfunction is present (myocarditis component dominant), avoid NSAIDs. If LV function is preserved and pericarditis features dominate, NSAIDs can be used cautiously.

Monitoring Modality	Rationale
Continuous telemetry	Detect arrhythmias (VT/VF, heart block) early — myocarditis can deteriorate acutely
Serial echocardiography	Track LV function recovery or deterioration
Serial troponin / CRP	Monitor resolution of myocardial necrosis and inflammation
Repeat cardiac MRI	Assess resolution of oedema (T2) and scar burden (LGE) at 3–6 months → guides return-to-activity decisions

2. Heart Failure Management (The Core of Treatment)

Treatment of HF and arrhythmia is the mainstay ^[1]^[2]^[4]. Long-term therapy for HF: ACEI, ARB, BB, diuretic, spironolactone ^[11].

The HF management in myocarditis follows standard guideline-directed medical therapy (GDMT) for heart failure with reduced ejection fraction (HFrEF), because the pathophysiology of the resulting pump failure is identical — ↓contractility → neurohormonal activation (RAAS, SNS) → maladaptive remodelling → progressive HF.

Drug Class	Examples	MoA	Why It Helps in Myocarditis	Contraindications / Caveats
ACEI	Enalapril, Ramipril, Perindopril	Inhibit angiotensin-converting enzyme → ↓Angiotensin II → ↓vasoconstriction + ↓aldosterone → ↓afterload + ↓preload + ↓remodelling	Neurohormonal blockade prevents maladaptive remodelling from RAAS activation. Start low, titrate up. Proven mortality benefit in HFrEF	Hyperkalaemia; renal artery stenosis; pregnancy; angioedema. Monitor K+ and creatinine
ARB	Losartan, Valsartan, Candesartan	Block AT₁ receptor → similar effect to ACEI but without bradykinin accumulation (so no cough)	Alternative to ACEI if ACEI-intolerant (cough, angioedema)	Same as ACEI except lower angioedema risk
ARNI	Sacubitril/Valsartan (Entresto)	Neprilysin inhibitor (sacubitril) → ↑natriuretic peptides (ANP, BNP) → ↑vasodilation + natriuresis + ↓fibrosis PLUS ARB component	Superior to ACEI alone in HFrEF (PARADIGM-HF trial). Can be used once stable on ACEI/ARB. 36-hour washout period between ACEI and ARNI to avoid angioedema	Cannot use with ACEI (angioedema risk); needs adequate BP to tolerate
Beta-blocker (BB)	Bisoprolol, Carvedilol, Metoprolol succinate	Block β₁-adrenergic receptors on cardiomyocytes → ↓HR + ↓myocardial O₂ demand + ↓catecholamine toxicity + ↓remodelling	Counters chronic sympathetic activation that drives maladaptive remodelling. Start low, titrate slowly. Proven mortality benefit	Do NOT initiate in acute decompensation — the failing heart depends on sympathetic drive acutely. Start only when patient is euvolaemic and haemodynamically stable. Contraindicated in cardiogenic shock, severe bradycardia, decompensated HF
Diuretics	Furosemide (loop), Hydrochlorothiazide (thiazide)	Loop: inhibit Na⁺/K⁺/2Cl⁻ co-transporter in thick ascending limb → ↑natriuresis → ↓volume → ↓preload	Relieve congestion (dyspnoea, oedema) — symptomatic benefit only, no mortality benefit. IV furosemide in acute decompensation; oral for maintenance	Over-diuresis → ↓preload → ↓CO → pre-renal AKI. Monitor weight, I/O, electrolytes (K⁺, Mg²⁺, Na⁺)
MRA (Mineralocorticoid receptor antagonist)	Spironolactone, Eplerenone	Block aldosterone receptor → ↓Na⁺/water retention + ↓myocardial fibrosis + ↓K⁺ wasting	Aldosterone drives myocardial fibrosis — blocking it reduces remodelling. Proven mortality benefit in HFrEF (RALES trial). Add when LVEF ≤35% despite ACEI + BB	Hyperkalaemia (especially with ACEI/ARB); eGFR < 30; K⁺ > 5.0. Spironolactone can cause gynaecomastia (anti-androgen effect) → use eplerenone if problematic
SGLT2 inhibitors	Dapagliflozin, Empagliflozin	Inhibit sodium-glucose co-transporter 2 in proximal tubule → glycosuria + osmotic diuresis + natriuresis + ↓interstitial volume	Latest addition to HFrEF therapy. Benefits in HFrEF independent of diabetes status (DAPA-HF, EMPEROR-Reduced). Also ↓inflammation, ↓oxidative stress	Genital infections (↑glucose in urine → candidiasis); DKA risk in T1DM. Generally well tolerated. Now part of the "four pillars" of HFrEF therapy
Hydralazine + Isosorbide dinitrate	H-ISDN	Hydralazine: arteriolar vasodilator → ↓afterload. ISDN: venodilator → ↓preload	Alternative for patients who cannot tolerate ACEI/ARB (e.g. severe renal impairment, hyperkalaemia). A-HeFT trial showed benefit in Black patients	Headache, hypotension, reflex tachycardia
Ivabradine	Ivabradine	Selective If channel blocker in SA node → ↓HR without ↓inotropy or ↓BP	If HR remains > 70 bpm despite maximally tolerated BB in sinus rhythm. Pure chronotrope without negative inotropic effect	Only works in sinus rhythm (If channels are in SA node). Not useful in AF
Digoxin	Digoxin	Inhibits Na⁺/K⁺-ATPase → ↑intracellular Ca²⁺ → mild +ve inotropy + ↑vagal tone → ↓HR	Used occasionally for rate control in AF with HF, or for symptom control in refractory HF. No mortality benefit — symptomatic only. Narrow therapeutic index	Digoxin toxicity: N/V, xanthopsia (yellow vision), arrhythmias (bigeminy, bidirectional VT). Toxicity ↑ by hypokalaemia, renal impairment, amiodarone

The 2022 ESC / 2024 updated "four pillars" of HFrEF therapy are: ACEI/ARB/ARNI + BB + MRA + SGLT2i — all should be initiated early and uptitrated to target doses.

GC High Yield — Management of DCM from Myocarditis

From GC 069 (Inherited Cardiac Conditions) — Management of DCM ^[18]:

Specific therapies e.g. immunosuppressants for autoimmune disease
No exercise for 3–6 months after myocarditis
Leisure-time activities only if high risk for life-threatening arrhythmias
Intractable ventricular arrhythmias / heart failure: LVAD / heart transplant
LVEF ≤35% or history of sustained VT/SCA → consider ICD

These points are directly examinable in the HKUMed in-house written papers.

The approach in children follows similar staging ^[10]:

Stage	Treatment
Stage A (at risk)	No specific treatment
Stage B (structural HD, no symptoms)	ACEI/ARB + BB (e.g. carvedilol)
Stage C (structural HD + symptoms)	ACEI/ARB + BB + MRA ± diuretics for fluid overload
Stage D (refractory)	Above + IV inotropes (e.g. dobutamine), diuretics, non-drug treatments, mechanical circulatory support

Arrhythmia	Acute Management	Chronic Management	Key Principle
Sinus tachycardia	Usually compensatory — treat HF, not the tachycardia directly	BB once stable	Do NOT acutely rate-control compensatory sinus tachycardia with BB in acute HF — the heart needs that rate to maintain CO
Atrial fibrillation	Rate control (BB or digoxin if HF); cardioversion if haemodynamically unstable	Anticoagulation if CHA₂DS₂-VASc ≥ 2 (men) or ≥ 3 (women)	Standard AF management applies
VT / VF	ACLS protocol: defibrillation + amiodarone. IV lidocaine as alternative	ICD if persistent risk (LVEF ≤35% after ≥3 months optimal therapy). Avoid implanting ICD during acute phase — LVEF may recover	Arrhythmias in acute myocarditis may be transient — wait for recovery before committing to permanent devices
Heart block (2nd/3rd degree)	Temporary transvenous pacing if symptomatic or haemodynamically significant	Permanent pacemaker only if block persists after acute phase resolves	Lyme disease → treat with IV ceftriaxone → heart block often resolves. Giant cell and sarcoidosis → may need permanent pacing

ICD Timing in Myocarditis — Common Exam Mistake

Do NOT implant an ICD during the acute phase of myocarditis. The LVEF may recover significantly as inflammation resolves. Current guidelines recommend waiting at least 3–6 months of optimal medical therapy before reassessing LVEF and arrhythmia burden for ICD indication (LVEF ≤35% despite ≥3 months GDMT). Implanting an ICD too early commits the patient to an unnecessary device with its own complications (inappropriate shocks, lead infections, generator changes).

4. Acute / Fulminant Myocarditis — Cardiogenic Shock Management

Severe HF: use of intravenous inotropic therapy or implantation of a ventricular assist device, heart transplantation ^[11]. Patients with refractory HF despite optimal medical therapy require mechanical circulatory support such as ventricular assist devices and cardiac transplantation ^[1]^[2].

Step	Action	Rationale
Airway	Assess and secure; RSI if needed	No airway → no oxygenation → no use having a circulation
Breathing	High flow O₂ (15L/min) with BVM with reservoir to keep SpO₂ > 94% ^[9]; CPAP/BiPAP or mechanical ventilation if needed	↑FiO₂ to maximise O₂ delivery; CPAP ↑intrathoracic pressure → ↓preload → ↓pulmonary congestion
Circulation	Sit patient upright ^[9]; IV access; haemodynamic monitoring	Upright position → venous pooling in lower extremities → ↓preload → ↓pulmonary congestion

Drug	MoA	Indication	Caveats
IV Dobutamine ^[9]^[10]	β₁ agonist → ↑contractility (inotropy) + mild β₂ vasodilation → ↓afterload	First-line inotrope for cardiogenic shock with adequate filling pressure	Tachycardia, arrhythmias. ↑myocardial O₂ demand. Short-term bridge only
Milrinone (Inodilator)	Phosphodiesterase-3 (PDE3) inhibitor → ↑cAMP → ↑contractility + vasodilation	Useful when β-receptors are downregulated (chronic HF); also ↓PVR → useful in RV failure	Hypotension (vasodilatory effect). Often used in paediatric myocarditis ^[10]
Noradrenaline	α₁ agonist → vasoconstriction + mild β₁ inotropy	When MAP is critically low despite inotropes — maintains coronary perfusion pressure	Excessive vasoconstriction → ↑afterload → ↑myocardial work. Use judiciously
Dopamine	Dose-dependent: low (renal vasodilation), medium (β₁ inotropy), high (α₁ vasoconstriction)	Alternative to dobutamine/noradrenaline in some centres	More arrhythmogenic than dobutamine; out of favour in modern practice
Levosimendan	Calcium sensitiser → ↑contractility without ↑O₂ demand; also K⁺-ATP channel opener → vasodilation	Used in some centres for acute decompensated HF	Not widely available; evidence base is limited compared to dobutamine

Mechanical circulatory support (e.g. IABP, LVAD, ECMO) for potentially reversible pump dysfunction ^[10]. This is critical in myocarditis because the disease is often self-limiting — if you can bridge the patient through the acute phase, the heart may recover.

Device	How It Works	Indication	Key Points
IABP (Intra-Aortic Balloon Pump)	Balloon inflates in diastole (↑coronary perfusion) and deflates in systole (↓afterload) — "counterpulsation"	Moderate cardiogenic shock as initial support; bridge to further MCS	Provides modest haemodynamic support (~0.5 L/min ↑CO). Less effective in severe shock
Impella	Axial-flow catheter pump placed across aortic valve → actively propels blood from LV to aorta	Severe cardiogenic shock; provides more support than IABP (2.5–5.5 L/min depending on model)	Placed percutaneously via femoral artery. Risk of haemolysis, limb ischaemia
VA-ECMO (Veno-Arterial Extracorporeal Membrane Oxygenation)	Blood drained from venous system → oxygenated externally → returned to arterial system. Provides both cardiac AND respiratory support	Fulminant myocarditis with refractory cardiogenic shock — the ultimate bridge to recovery or transplant	ECMO provides prolonged cardiorespiratory support for oxygenation of blood ^[18]. Can maintain full circulatory support for days-weeks while awaiting myocardial recovery. Complications: limb ischaemia, bleeding, haemolysis, infection, LV distension (may need LV venting)
LVAD (Left Ventricular Assist Device)	Continuous-flow pump that unloads LV → assists blood flow from LV to aorta	Bridge to transplant or destination therapy in chronic refractory HF	Intractable ventricular arrhythmias / heart failure: LVAD / heart transplant ^[18]

Why MCS is So Important in Fulminant Myocarditis

Here's the paradox: fulminant myocarditis (the most dramatic and terrifying presentation) actually has a better long-term prognosis than subacute myocarditis — IF the patient survives the acute phase. The vigorous immune response that causes the acute shock also tends to clear the virus effectively, leading to better recovery. The problem is surviving the acute crash. That's where MCS (especially VA-ECMO) is life-saving — it keeps the patient alive during the immunological storm so the heart can heal. This is different from ischaemic cardiomyopathy, where the damage is permanent.

5. Aetiology-Specific Treatment (Immunosuppression and Targeted Therapy)

This is where the histological subtype (from EMB) or identified aetiology truly matters.

Immunosuppression is NOT proven to be effective in acute lymphocytic myocarditis or myocarditis with unspecified aetiology ^[1]^[2]^[4]. Viral myocarditis: unproven specific treatment ^[11].

Why not? In viral myocarditis, the immune response (Phase 2) is needed to clear the virus. Immunosuppression during active viral replication → ↑viral load → ↑myocardial damage. Multiple randomised trials (Myocarditis Treatment Trial, TIMIC) have not shown benefit of immunosuppression in idiopathic/lymphocytic myocarditis.

Indications of immunosuppressive therapy ^[1]^[2]:

Condition	Why Immunosuppression Works	Regimen
Giant cell myocarditis	Autoimmune process (multinucleated giant cells + CD4+ T cells) → rapidly fatal without treatment. Median survival 5.5 months untreated. No viral trigger to clear	Prednisolone + Cyclosporine (most evidence); or Prednisolone + Azathioprine. Even with treatment, transplant-free survival is poor (~50% at 5 years)
Eosinophilic myocarditis	Eosinophilic infiltration is the primary pathology → corticosteroids directly suppress eosinophil production and activation	Remove trigger (stop offending drug, treat parasitic infection) + Prednisolone. Usually responds well
Autoimmune or hypersensitivity myocarditis	Immune-mediated without active infection → immunosuppression dampens the autoimmune attack	Prednisolone alone or with steroid-sparing agent (azathioprine, MTX). Treat underlying autoimmune disease (SLE, RA, GPA)
Cardiac sarcoidosis	Non-caseating granulomas causing conduction disease and myocardial dysfunction	Prednisolone (first-line); steroid-sparing: MTX, azathioprine. Often needs pacemaker/ICD for conduction disease

Choices of immunosuppressants ^[1]^[2]:

Prednisolone alone
Prednisolone + Azathioprine
Prednisolone + Cyclosporine
IVIG (Intravenous immunoglobulin)

The decision tree from the lecture slides ^[11] is important:

EMB Result	PCR for Virus	Treatment
Active myocarditis — giant cell or autoreactive	Negative (no active viral genome)	Immunosuppression in PCR-negative cases ^[11]
Active myocarditis — lymphocytic	Positive (viral genome present)	IVIg in virus-positive cases ^[11]; NO immunosuppression (would ↑viral replication)
Fulminant myocarditis	Negative	Immunosuppression + MCS (intermittent assist device, ICDs) ^[11]

MoA: Pooled polyclonal IgG from thousands of donors → multiple mechanisms: neutralisation of viral particles, immunomodulation (↓inflammatory cytokines, ↓complement activation), blockade of Fc receptors on macrophages
Use in myocarditis: Evidence is mixed. Best evidence in paediatric viral myocarditis. Used in MIS-C/MIS-A (COVID-related inflammatory syndrome) ^[6]. Some use as empiric therapy in fulminant myocarditis while awaiting EMB results
Dose: Typically 2 g/kg as a single dose or divided over 2 days
Side effects: Anaphylaxis (especially in IgA-deficient patients), headache, thrombotic events, renal impairment

Aetiology	Specific Treatment	Key Point
Lyme disease (Borrelia)	IV ceftriaxone × 14–21 days	AV block often resolves with antibiotic treatment alone; temporary pacing as bridge
Chagas disease (T. cruzi)	Benznidazole or nifurtimox in acute phase	Chronic Chagas cardiomyopathy: standard HF therapy ± transplant. Antiparasitic drugs have limited benefit in chronic phase
Diphtheria	Diphtheria antitoxin + antibiotics (penicillin or erythromycin)	Antitoxin neutralises circulating toxin; antibiotics eliminate organism
HIV	Antiretroviral therapy (ART)	May improve myocardial function by reducing viral load and immune activation
COVID-19 / MIS-A	Steroid, IVIg, supportive therapy ^[6]	Similar to Kawasaki disease protocol in children (MIS-C)
Checkpoint inhibitor myocarditis	Immediate cessation of ICI + high-dose IV methylprednisolone (1 g/day × 3–5 days) ± mycophenolate, abatacept, or alemtuzumab	Life-threatening — mortality ~25–50%. Permanently discontinue ICI. Do NOT rechallenge

Heart transplantation is the final option for patients with:

Intractable ventricular arrhythmias / heart failure: LVAD / heart transplant ^[18]
Refractory cardiogenic shock despite MCS
Progressive DCM with NYHA class III–IV symptoms despite maximal therapy
Giant cell myocarditis refractory to immunosuppression (recurrence in transplanted heart occurs in ~20–25%, but can be managed with immunosuppression)

Indications (general for HF, applicable to myocarditis-related DCM) ^[16]:

ICD indicated in patients with life expectancy > 1 year with good functional status who have haemodynamically not tolerated VT/VF, or NYHA Class II–III HF symptoms and LVEF ≤35% despite optimal GDMT for ≥3 months ^[16]
CRT indicated in patients with symptomatic HF with LVEF ≤35% and widened QRS particularly with LBBB configuration ^[16]

Timepoint	Action	Purpose
Acute phase (0–2 weeks)	Inpatient telemetry, serial troponin/CRP, daily clinical assessment	Monitor for deterioration, arrhythmia
Early recovery (2–12 weeks)	Serial echo q2–4 weeks; transition to oral HF medications	Track LVEF recovery; uptitrate GDMT
3–6 months	Repeat cardiac MRI; Holter monitoring; exercise testing	Assess resolution of inflammation (T2 oedema), scar burden (LGE); guide return-to-activity
12 months and beyond	Annual echo + clinical review; genetic counselling if DCM persists	~50% recover fully; ~25% have persistent LV dysfunction; ~25% develop progressive DCM

Scenario	Key Management	What NOT to Do
Mild / subclinical myocarditis	Activity restriction × 3–6 months; avoid NSAIDs/alcohol; monitor	Do not ignore — even mild myocarditis can cause SCD with exertion
Myocarditis with stable HF	GDMT: ACEI/ARB + BB + MRA + SGLT2i; diuretics for congestion	Do not give NSAIDs; do not implant ICD during acute phase
Fulminant myocarditis / cardiogenic shock	ICU; inotropes → MCS (ECMO/LVAD) → bridge to recovery or transplant	Do not give up — fulminant has best long-term prognosis if patient survives
Giant cell myocarditis	Immunosuppression (steroids + cyclosporine) + standard HF Rx + transplant evaluation	Do not treat as simple viral myocarditis — it will be fatal without immunosuppression
Eosinophilic myocarditis	Remove trigger + steroids	Do not give immunosuppression without removing offending agent first
Viral / lymphocytic myocarditis	Supportive care only — no proven specific antiviral or immunosuppressive therapy ^[4]^[11]	Do not give immunosuppression (may ↑viral replication and worsen outcome)

High Yield Summary — Management of Myocarditis

Supportive care is first-line ^[4]^[11]. Treatment is supportive with standard heart failure therapy ^[8].
HF therapy: ACEI/ARB, BB, diuretic, spironolactone (MRA) ^[11] + SGLT2i (modern addition).
AVOID: NSAIDs (↑necrosis + ↑mortality), exercise (arrhythmia risk × 3–6 months), alcohol ^[1]^[2]^[4].
Severe HF: IV inotropic therapy (dobutamine), VAD, heart transplantation ^[11].
Immunosuppression ONLY for: giant cell, eosinophilic, autoimmune/hypersensitivity myocarditis, cardiac sarcoidosis ^[1]^[2]. NOT effective in viral/lymphocytic or unspecified myocarditis ^[1]^[2].
Immunosuppression in PCR-negative cases; IVIg in virus-positive cases ^[11].
No exercise for 3–6 months ^[18]. Intractable arrhythmias/HF → LVAD / transplant ^[18].
ICD: Wait ≥3 months optimal GDMT before assessing indication (LVEF ≤35%). Do NOT implant during acute phase.
Fulminant myocarditis: Worst acutely but best long-term prognosis if survived — bridge with MCS.

Active Recall - Management of Myocarditis

References

^[1] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf — Cardiovascular Diseases, Myocarditis, Treatment section (p.426) ^[2] Senior notes: MBBS Final MB (Pediatrics) (Felix PY Lai).pdf — Cardiovascular Diseases, Myocarditis, Treatment section (p.294) ^[3] Senior notes: Maksim Medicine Notes.pdf — Cardiology section 1.10, Myocarditis (p.40) ^[4] Senior notes: Ryan Ho Cardiology.pdf — Section 3.4.1 Myocarditis, Management (p.165) ^[6] Senior notes: Ryan Ho Respiratory.pdf — COVID-19 Complications, MIS-A section (p.58) ^[8] Senior notes: learning_points_output.txt — Cardiology, Three Cases of Dyspnea (Learning Point 2) ^[9] Senior notes: Ryan Ho Critical Care.pdf — Management of Cardiogenic Shock (p.22) ^[10] Senior notes: Adrian Lui Pediatrics Notes.pdf — Approach to Pediatric Heart Failure, Management (p.200) ^[11] Lecture slides: Three Cases SOB 20211.pdf — Myocarditis: Treatment (p.27, 33) ^[16] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf — DCM Treatment section (p.535) ^[18] Lecture slides: GC 069. Inherited Cardiac conditions.pdf — Management of DCM (p.9)

Complications of Myocarditis

The complications of myocarditis are best understood by thinking about what happens when you damage the three key functions of the myocardium: contraction (pump failure), electrical conduction (arrhythmia), and structural integrity (dilatation and remodelling). Every complication flows logically from one of these three functional deficits.

1. Dilated Cardiomyopathy (DCM) — The Most Important Chronic Complication

Dilated cardiomyopathy (DCM) is the single most important complication of myocarditis and the one most commonly asked about in exams ^[3].

Inflammatory cardiomyopathy is defined as myocarditis accompanied by cardiac dysfunction which can lead to dilated cardiomyopathy in the long run ^[1]^[2].

The transition from myocarditis to DCM represents a failure to heal:

Phase 3 failure (as discussed in pathophysiology): If the immune response does not resolve — either because of viral persistence, ongoing autoimmunity (molecular mimicry), or inadequate viral clearance — there is continued myocyte loss over weeks to months.
Myocyte replacement by fibrosis: Dead cardiomyocytes cannot regenerate (cardiomyocytes have negligible proliferative capacity in adults). They are replaced by collagen scar tissue laid down by fibroblasts.
Neurohormonal activation: ↓CO from myocyte loss → activation of RAAS (angiotensin II, aldosterone) and SNS (noradrenaline). These systems initially compensate (↑HR, ↑contractility, ↑preload, ↑afterload) but are maladaptive chronically → further myocyte death, hypertrophy, fibrosis, and apoptosis.
Ventricular remodelling: Progressive loss of contractile tissue + fibrosis + neurohormonal stimulation → the ventricle dilates and becomes spherical → wall stress increases (Laplace's law: wall stress = pressure × radius / 2 × wall thickness) → further dilatation → vicious cycle.
End-stage: A thin-walled, dilated, poorly contractile ventricle — the hallmark of DCM.

~9% of all DCM cases are attributable to prior myocarditis ^[4] — making it the third most common cause after idiopathic/familial (~50%) and ischaemic (~7%)
Chronic myocarditis (both "chronic active" and "chronic persistent" forms) leads to chronic HF ^[11]
The chronic phase: dilated heart with evidence of fibrosis — not everyone goes through all phases ^[19]
Risk factors for progression to DCM: persistent LGE on cardiac MRI (scar), persistent LV dysfunction at 3–6 months, giant cell histology, viral persistence on EMB PCR
Prognosis: once DCM is established, 5-year mortality is ~20%. Management follows standard HFrEF guidelines

High Yield — The Myocarditis → DCM Pathway

The exam-relevant teaching point is the classic clinical vignette: a 40-year-old with preceding flu-like illness who develops heart failure with displaced apex, S3 gallop, and mitral regurgitation from ventricular dilatation ^[8]. This represents viral myocarditis that has progressed (or is in the process of progressing) to dilated cardiomyopathy. When you see unexplained DCM in a young patient, always ask about a preceding viral illness weeks to months earlier.

Heart failure is both a presenting feature and a complication of myocarditis. The distinction is temporal:

Type	Mechanism	Clinical Picture
Acute HF / ADHF	Direct myocyte inflammation + oedema + necrosis → abrupt ↓contractility → acute pump failure	SOB, tachycardia out of proportion to fever, elevated JVP ^[3]. Pulmonary oedema. May progress to cardiogenic shock
Chronic HF	Post-inflammatory DCM → progressive neurohormonal maladaptation (as described above)	SOBOE, orthopnoea, PND, peripheral oedema, fatigue — progressive over months-years. Chronic heart failure: dilated cardiomyopathy as a chronic insult ^[3]

Why does acute HF occur? The mechanism is ↓contractility from the disease itself:

Myocyte necrosis → fewer contractile units → ↓systolic function
Myocardial oedema → ↑wall stiffness → ↓diastolic compliance → ↑filling pressures
Inflammatory cytokines (TNF-α, IL-1β, IL-6) → direct negative inotropic effect (↓calcium cycling in cardiomyocytes)
Combined: ↓CO + ↑filling pressures → both forward failure (hypoperfusion) and backward failure (congestion) ^[9]

3. Arrhythmias

Arrhythmias are the leading cause of death in acute myocarditis and a major long-term complication.

Mechanism	Arrhythmia Type	Explanation
Electrical heterogeneity from patchy inflammation/necrosis	Ventricular tachycardia (VT), ventricular fibrillation (VF)	Normal myocardium conducts uniformly. Inflamed/necrotic patches have different conduction velocities and refractory periods from healthy tissue → re-entry circuits → VT/VF
Inflammation of conduction tissue	AV block (1st, 2nd, 3rd degree), bundle branch block	The AV node, His bundle, and bundle branches are specialised cardiomyocytes embedded within the myocardium. If the inflammatory infiltrate involves these structures → conduction delay or block
Atrial dilatation + inflammation	Atrial fibrillation (AF), atrial flutter, ectopic atrial tachycardia	Atrial myocarditis → atrial electrical remodelling → multiple wavelet re-entry or ectopic foci → AF
Triggered activity from afterdepolarisations	Premature ventricular complexes (PVCs), polymorphic VT	Intracellular calcium overload in damaged myocytes → delayed afterdepolarisations (DADs) → triggered beats. Catecholamines (exercise, stress) worsen this → basis for the exercise restriction rule
Scar-related re-entry (chronic)	Monomorphic VT (late complication)	Healed myocarditis leaves patchy fibrosis → stable re-entry circuits → recurrent VT, sometimes years after the acute episode

Fulminant myocarditis: Shock, HF, dyspnea, severe rhythm disturbances, SCD from HF or recovery ^[11].

Aetiology	Characteristic Arrhythmia	Why
Lyme disease	Complete (3rd degree) AV block	Borrelia burgdorferi has tropism for conduction tissue, particularly the AV node
Cardiac sarcoidosis	AV block + VT	Granulomas preferentially deposit in the basal septum where the His bundle runs
Giant cell myocarditis	VT/VF + AV block	Extensive myocyte destruction with multinucleated giant cells → large areas of electrical disruption
Chagas disease	RBBB + left anterior fascicular block	Fibrosis of the right bundle and left anterior fascicle is characteristic of chronic Chagas cardiomyopathy

4. Sudden Cardiac Death (SCD)

Myocarditis is one of the major causes of sudden, unexpected death in adults < 40 years (~20% of cases) ^[4].

VT/VF: The most common mechanism. Inflamed myocardium → electrical instability → VT degenerating to VF → cardiac arrest → death within minutes if not defibrillated
Complete heart block with asystole: If the conduction system is severely affected → no ventricular escape rhythm → asystole
Electromechanical dissociation (PEA): Massive myocardial inflammation → coordinated electrical activity but no effective contraction

Young athletes (exercise + catecholamines + inflamed myocardium = perfect storm for VT/VF) — this is why no exercise for 3–6 months after myocarditis ^[18]
Patients with fulminant presentation
Giant cell myocarditis (median survival 5.5 months without immunosuppression)
Patients with persistent ventricular arrhythmias
Those who ignore activity restrictions during the acute phase

SCD in Young Athletes — The Ultimate Exam Scenario

A previously healthy young athlete collapses during a match and dies. Autopsy shows lymphocytic myocarditis. This vignette is a classic exam scenario. The teaching points are: (1) myocarditis is a leading cause of SCD in young athletes, (2) exercise in inflamed myocardium provokes fatal arrhythmias via catecholamine-driven triggered activity and re-entry, (3) athletes with recent viral illness + cardiac symptoms (chest pain, palpitations, syncope, disproportionate fatigue) must be screened and activity-restricted.

Cardiogenic shock: due to cardiac pump failure → ↓CO ^[9]. Myocarditis is one of the listed cardiomyopathic causes alongside MI, ADHF from DCM, and drug-induced cardiomyopathy ^[9].

Pathophysiology

Massive, diffuse myocardial inflammation → severe ↓contractility → ↓↓CO → ↓MAP → inadequate organ perfusion.

Feature	Mechanism
Forward failure: pallor, cold extremities, delayed capillary refill, oliguria, altered consciousness ^[9]	↓CO → ↓tissue perfusion → compensatory vasoconstriction (cool skin) + inadequate renal perfusion (oliguria) + cerebral hypoperfusion (confusion)
Backward failure: dyspnoea, wheeze, pink frothy sputum, crackles, ↑JVP, displaced apex, gallop ^[9]	↑LVEDP → pulmonary congestion; ↑RVEDP → systemic venous congestion

Cardiogenic shock in myocarditis = medical emergency requiring ICU admission, inotropes, and potentially MCS (ECMO/LVAD). The silver lining: fulminant myocarditis with cardiogenic shock paradoxically has better long-term prognosis than subacute myocarditis if the patient survives, because the vigorous immune response tends to clear the virus effectively.

Myocarditis creates a pro-thrombotic state through multiple mechanisms:

Mechanism	Consequence	Clinical Manifestation
LV dilatation + ↓contractility → blood stasis	Intracardiac (usually LV apical) thrombus formation — Virchow's triad: stasis + endothelial injury + hypercoagulability are all present	Stroke (embolism to cerebral arteries), limb ischaemia (embolism to peripheral arteries), mesenteric ischaemia
Endocardial inflammation → exposed subendocardial collagen	Direct endothelial injury activates coagulation cascade	Mural thrombus adherent to inflamed ventricular wall
Systemic inflammation → pro-coagulant state	↑tissue factor, ↑fibrinogen, ↓protein C/S	Both arterial and venous thromboembolism
AF from atrial involvement	Atrial stasis in non-contracting fibrillating atria	Stroke, systemic embolism

Prevention: Anticoagulation should be considered in patients with:

Documented intracardiac thrombus (absolute indication)
Severely reduced LVEF ( < 30–35%) with significant LV dilatation
AF

Because the pericardium sits immediately adjacent to the myocardium, myocarditis frequently involves the pericardium too — this is myopericarditis.

Complication	Mechanism	Clinical Features
Pericardial effusion	Pericardial inflammation → ↑capillary permeability → exudative fluid accumulation in pericardial space	Pericardial effusion occurs in up to 20% of fulminant myocarditis and up to 10% of acute/chronic forms ^[11]. Usually small-moderate and self-limiting
Cardiac tamponade	Rapid fluid accumulation → pericardial pressure exceeds filling pressure → ↓venous return → ↓CO	Beck's triad: hypotension, distended neck veins, muffled heart sounds. Pulsus paradoxus ( > 10 mmHg drop in SBP during inspiration). Rare but life-threatening — requires urgent pericardiocentesis
Constrictive pericarditis	Chronic pericardial inflammation → fibrosis + calcification → rigid pericardium → impaired diastolic filling	Very rare late complication. Kussmaul sign, pericardial knock, elevated JVP with prominent y descent

While acute conduction disturbances (discussed under arrhythmias above) often resolve with the inflammation, some patients develop persistent conduction disease requiring permanent pacing:

Situation	Mechanism	Management
Persistent complete heart block	Irreversible damage to AV node/His bundle from inflammation → fibrosis of conduction tissue	Permanent pacemaker implantation if block persists > 7–10 days after acute phase or after treating reversible causes (e.g. Lyme)
Cardiac sarcoidosis	Non-caseating granulomas in conduction system	Often requires pacemaker ± ICD (high risk of VT)
Giant cell myocarditis	Extensive myocyte destruction involving conduction tissue	Temporary pacing acutely; permanent device if survives; often requires transplant evaluation

Myocarditis can recur, especially in:

Autoimmune myocarditis (SLE, sarcoidosis) — flares of the underlying disease trigger recurrent cardiac inflammation
Giant cell myocarditis post-transplant — recurrence in transplanted heart occurs in ~20–25% of cases
Re-exposure to offending agent — drug-induced or hypersensitivity myocarditis will recur if the patient is re-exposed
MCTD — morbidity includes flares of polymyositis, pericarditis, pleurisy, myocarditis ^[15]

Treatment	Potential Complication
ACEI/ARB	Hyperkalaemia, AKI, hypotension, teratogenicity
Beta-blockers	Bradycardia, hypotension, bronchospasm (non-selective), decompensation if started during acute HF
Diuretics	Electrolyte derangements (hypokalaemia, hyponatraemia, hypomagnesaemia), prerenal AKI, ototoxicity (loop diuretics)
Immunosuppression (steroids)	Infection, hyperglycaemia, osteoporosis, Cushing syndrome, adrenal suppression, GI bleeding
VA-ECMO / MCS	Limb ischaemia, bleeding, haemolysis, infection, LV distension, thrombosis
EMB	Cardiac perforation (~1%), arrhythmia, vascular access complications
ICD	Inappropriate shocks, lead infection/fracture, generator changes, psychological impact

Prognosis varies widely depending on underlying cause and presenting clinical syndrome ^[4]:

Clinical Category	Prognosis	Key Determinant
Asymptomatic or mild subclinical disease	Good prognosis — spontaneous recovery ^[4]	Most common outcome. ~50% have complete recovery of LV function
Acute myocarditis with moderate LV dysfunction	Generally favourable; ~25% have persistent mild LV dysfunction	Degree of LGE on MRI predicts residual dysfunction
Fulminant myocarditis	Worst acutely (high risk of death from shock/arrhythmia) but best long-term prognosis if patient survives ^[4]	The vigorous immune response clears the virus; if bridged with MCS → excellent recovery
Progressive DCMP and HF in patients with complicated disease ^[4]	~25% develop progressive DCM; 5-year mortality ~20%	Persistent LV dysfunction at 3–6 months, large scar on MRI
Giant cell myocarditis	Worst overall prognosis — fulminant myocarditis (arrhythmia, ADHF, death) especially in giant cell myocarditis ^[4]. Median survival 5.5 months without immunosuppression	Requires aggressive immunosuppression and often transplant. Recurrence in transplanted heart ~20–25%
Chronic active / persistent myocarditis	Chronic HF ^[11] — slow progressive decline	Ongoing low-grade inflammation → cumulative myocyte loss

High Yield Summary — Complications of Myocarditis

Dilated cardiomyopathy (DCM) ^[3] — the most important chronic complication; ~9% of all DCM attributable to prior myocarditis. Mechanism: failed immune clearance → ongoing myocyte loss → fibrosis → ventricular dilatation → neurohormonal maladaptation.
Heart failure — acute (from direct myocyte damage, oedema, inflammatory cytokines) or chronic (from DCM progression).
Arrhythmias — leading cause of death. VT/VF from electrical heterogeneity and re-entry; AV block from conduction system inflammation; AF from atrial involvement.
Sudden cardiac death — ~20% of SCD in adults < 40y ^[4]. Driven by VT/VF. Why exercise restriction matters.
Cardiogenic shock — fulminant myocarditis; paradoxically better long-term prognosis if survived.
Thromboembolism — from stasis (dilated LV) + endocardial injury + systemic inflammation. Can cause stroke, limb ischaemia.
Pericardial complications — effusion (up to 20% in fulminant), rarely tamponade or constrictive pericarditis.
Conduction disease — may require permanent pacing (especially in Lyme, sarcoidosis, giant cell myocarditis).
Recurrence — in autoimmune myocarditis, drug-related (re-exposure), giant cell (post-transplant ~20–25%).

Active Recall - Complications of Myocarditis

References

^[1] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf — Cardiovascular Diseases, Myocarditis (p.423, 426) ^[2] Senior notes: MBBS Final MB (Pediatrics) (Felix PY Lai).pdf — Cardiovascular Diseases, Myocarditis (p.291, 294) ^[3] Senior notes: Maksim Medicine Notes.pdf — Cardiology section 1.10, Myocarditis (p.40) ^[4] Senior notes: Ryan Ho Cardiology.pdf — Section 3.4.1 Myocarditis (p.165); Section 3.4.2.2 DCM (p.169) ^[8] Senior notes: learning_points_output.txt — Cardiology, Three Cases of Dyspnea (Learning Point 2) ^[9] Senior notes: Ryan Ho Critical Care.pdf — Management of Cardiogenic Shock (p.16, 22) ^[11] Lecture slides: Three Cases SOB 20211.pdf — Myocarditis classification table (p.27); Diagnosis (p.32); Treatment (p.33) ^[15] Senior notes: Ryan Ho Rheumatology.pdf — MCTD, Prognosis (p.87) ^[18] Lecture slides: GC 069. Inherited Cardiac conditions.pdf — Management of DCM (p.9) ^[19] Lecture slides: Three Cases SOB 20211.pdf — Pathogenesis (p.30)

High Yield Summary

Definition: Myocarditis = non-ischaemic inflammatory disease of myocardium. Inflammatory cardiomyopathy = myocarditis + cardiac dysfunction → can lead to DCM.

Epidemiology: Young adults (20–40), M > F. Major cause of sudden cardiac death in < 40y (~20%). In HK: viral causes predominate (Adenovirus, Echovirus, Coxsackie virus).

Pathophysiology — 3 Phases: (1) Direct viral myocyte injury → (2) Adaptive immunity + molecular mimicry → (3) Remodelling ± resolution vs DCM.

Clinical Features:

Prodrome: Viral flu-like illness weeks before cardiac symptoms
Symptoms: Chest pain (usually pericardial), dyspnoea, palpitations, syncope, fatigue
Signs: Tachycardia (out of proportion to fever), S3, displaced apex, functional MR, ↑JVP, lung crackles
Fulminant: Cardiogenic shock features (cold peripheries, ↓BP, oliguria, altered consciousness)

Key Pearls:

Chest pain in myocarditis = usually concomitant pericarditis
Tachycardia out of proportion to fever = myocarditis until proven otherwise
Avoid exertion → risk of fatal ventricular arrhythmias
DON'T give NSAIDs (↓PG → may worsen myocardial function + ↑necrosis)
EMB = gold standard but rarely done (1% perforation risk, usually doesn't change management)

High Yield Summary — Differential Diagnosis of Myocarditis

The DDx depends on how myocarditis presents:

ACS-mimic → DDx: AMI, pericarditis, PE, aortic dissection, Takotsubo
- Key action: Coronary angiography/CT coronary angiogram to rule out CAD ^[8]^[11]
- Key differentiators: viral prodrome, young age, no CVS risk factors, non-coronary LGE on MRI
New-onset HF → DDx: All causes of DCM (idiopathic/familial, ischaemic, alcoholic, peripartum, tachycardia-mediated, chemotherapy-related, valvular)
- Key action: Exclude ischaemic cause with angiography; cardiac MRI for inflammatory pattern
Arrhythmia/SCD → DDx: Inherited arrhythmia syndromes (Brugada, Long QT, ARVC, HCM), primary VT
- Key differentiators: Family history, baseline ECG patterns, fibrofatty replacement vs inflammation on MRI
Paediatric HF → DDx varies by age: neonatal (duct-dependent CHD, sepsis), infant (L-to-R shunts, ALCAPA), older child (ARF, cardiomyopathy, IE)

High Yield Summary — Management of Myocarditis

Supportive care is first-line ^[4]^[11]. Treatment is supportive with standard heart failure therapy ^[8].
HF therapy: ACEI/ARB, BB, diuretic, spironolactone (MRA) ^[11] + SGLT2i (modern addition).
AVOID: NSAIDs (↑necrosis + ↑mortality), exercise (arrhythmia risk × 3–6 months), alcohol ^[1]^[2]^[4].
Severe HF: IV inotropic therapy (dobutamine), VAD, heart transplantation ^[11].
Immunosuppression ONLY for: giant cell, eosinophilic, autoimmune/hypersensitivity myocarditis, cardiac sarcoidosis ^[1]^[2]. NOT effective in viral/lymphocytic or unspecified myocarditis ^[1]^[2].
Immunosuppression in PCR-negative cases; IVIg in virus-positive cases ^[11].
No exercise for 3–6 months ^[18]. Intractable arrhythmias/HF → LVAD / transplant ^[18].
ICD: Wait ≥3 months optimal GDMT before assessing indication (LVEF ≤35%). Do NOT implant during acute phase.
Fulminant myocarditis: Worst acutely but best long-term prognosis if survived — bridge with MCS.

High Yield Summary — Complications of Myocarditis

Dilated cardiomyopathy (DCM) ^[3] — the most important chronic complication; ~9% of all DCM attributable to prior myocarditis. Mechanism: failed immune clearance → ongoing myocyte loss → fibrosis → ventricular dilatation → neurohormonal maladaptation.
Heart failure — acute (from direct myocyte damage, oedema, inflammatory cytokines) or chronic (from DCM progression).
Arrhythmias — leading cause of death. VT/VF from electrical heterogeneity and re-entry; AV block from conduction system inflammation; AF from atrial involvement.
Sudden cardiac death — ~20% of SCD in adults < 40y ^[4]. Driven by VT/VF. Why exercise restriction matters.
Cardiogenic shock — fulminant myocarditis; paradoxically better long-term prognosis if survived.
Thromboembolism — from stasis (dilated LV) + endocardial injury + systemic inflammation. Can cause stroke, limb ischaemia.
Pericardial complications — effusion (up to 20% in fulminant), rarely tamponade or constrictive pericarditis.
Conduction disease — may require permanent pacing (especially in Lyme, sarcoidosis, giant cell myocarditis).
Recurrence — in autoimmune myocarditis, drug-related (re-exposure), giant cell (post-transplant ~20–25%).

Myocarditis

1. Definition

2. Epidemiology

2.1 Incidence and Prevalence

2.2 Demographics

2.3 Hong Kong Context

3. Anatomy and Function — The Myocardium

3.1 Structure

3.2 Function

4. Etiology

4.1 Infectious Causes

4.1.1 Viral (Most Common Overall)

4.1.2 Bacterial

4.1.3 Fungal

4.1.4 Parasitic

4.2 Non-Infectious Causes

4.2.1 Autoimmune / Systemic

4.2.2 Drug-Induced / Toxic

4.2.3 Hypersensitivity Myocarditis

4.2.4 Other Toxic / Physical Causes

5. Pathophysiology

Phase 1: Viral Entry and Direct Myocyte Injury (Days 0–3)

Phase 2: Adaptive Immune Response (Days 4–14)

Phase 3: Cardiac Remodelling (Weeks to Months)

Specific Pathophysiological Mechanisms by Etiology

6. Classification

6.1 By Temporal Course (Clinical Classification)

6.2 By Histology (Dallas Criteria, 1987)

6.3 By Histological Pattern (Etiology-Based)

6.4 By Clinical Presentation Pattern [4]

7. Clinical Features

7.1 Symptoms

7.1.1 Prodromal Phase (Preceding Viral Illness)

7.1.2 Cardiac Symptoms

7.1.3 Systemic Symptoms

7.2 Signs

7.2.1 General Examination

7.2.2 Cardiovascular Examination

7.2.3 Signs of Cardiogenic Shock (Fulminant Myocarditis)

7.2.4 Signs Specific to Certain Etiologies

7.3 Paediatric-Specific Features [7][10]

7.4 Why the Clinical Spectrum is So Wide

Active Recall - Myocarditis (Definition to Clinical Features)

References

Why is the DDx So Broad?

Approach to the DDx — By Presenting Syndrome

Syndrome A: ACS-like Presentation (Chest Pain + ↑Troponin + ST/T Changes)

Syndrome B: New-Onset Heart Failure Presentation (Dyspnoea + Ventricular Dysfunction)

Syndrome C: Arrhythmia / Shock / Sudden Death Presentation

Differential Diagnosis in Paediatric Age Groups

Systematic DDx Table — Organized by the Feature That Overlaps with Myocarditis

Approach Algorithm — How to Work Through the DDx

Key Distinguishing Features — Myocarditis vs Its Main Mimics

Special Differentials Worth Knowing for Exams

1. Cardiac Sarcoidosis vs Myocarditis

2. Giant Cell Myocarditis vs Lymphocytic Myocarditis

3. Myocarditis in the Setting of Systemic Disease

Active Recall - Differential Diagnosis of Myocarditis

Why Diagnosing Myocarditis is Difficult

Diagnostic Criteria

1. Clinical Diagnostic Framework (ESC 2013 Position Statement)

2. Histopathological Criteria — Dallas Criteria (1987)

3. Immunohistochemical (IHC) Criteria — World Heart Federation

4. Cardiac MRI Criteria — Updated Lake Louise Criteria (2018)

Comparison of Dallas vs Lake Louise vs IHC Criteria

Diagnostic Algorithm

Investigation Modalities — Detailed Breakdown

1. Blood Tests

1a. Inflammatory Markers

1b. Cardiac Biomarkers

1c. BNP / NT-proBNP

1d. Aetiological Workup

2. Electrocardiogram (ECG)

3. Chest X-Ray (CXR)

4. Echocardiography

5. Cardiac MRI (CMR) — The Key Non-Invasive Diagnostic Tool

6. Coronary Angiography / CT Coronary Angiogram

7. Endomyocardial Biopsy (EMB) — The Gold Standard

Procedure

Indications — When to Perform EMB