Myocarditis: Physiology, Causes, Pathophysiology, Symptoms, Diagnosis, Management and Prevention

Myocarditis

~Introduction

Myocarditis is an inflammatory disease of the heart muscle (myocardium) that leads to injury or necrosis of cardiac myocytes. The condition can result from a wide range of infectious and non-infectious causes, including viruses, bacteria, autoimmune disorders, toxins, and drugs. Depending on its severity, myocarditis can present as a mild, self-limiting illness or progress to severe heart failure, arrhythmias, or even sudden cardiac death.

Myocarditis affects people of all ages, but it is particularly significant in young adults and athletes, where it is a leading cause of sudden cardiac arrest. The global incidence is difficult to determine because many mild cases go undiagnosed, but autopsy studies suggest myocarditis contributes to up to 10–20% of sudden unexpected deaths in young adults.

~Anatomy and Physiology Review

The myocardium is the muscular middle layer of the heart wall, responsible for the contraction and relaxation that pump blood throughout the body. When the myocardium becomes inflamed, its ability to contract efficiently is impaired. This leads to reduced cardiac output, electrical instability, and, in severe cases, cardiogenic shock or dilated cardiomyopathy.

Inflammation may affect:

• Focal areas (focal myocarditis)

• Diffuse areas (diffuse myocarditis)

• The entire heart wall (pancarditis, when endocardium and pericardium are also involved)

~Etiology (Causes)

Myocarditis has numerous causes, broadly classified into infectious and non-infectious origins.

1. Infectious Causes

Viral Infections (most common)

Viruses are responsible for the majority of myocarditis cases worldwide. Common viral agents include:

• Coxsackievirus B and Echovirus (enteroviruses)

• Adenovirus

• Parvovirus B19

• Human Herpesvirus-6 (HHV-6)

• Cytomegalovirus (CMV)

• Epstein–Barr Virus (EBV)

• Influenza

• Hepatitis C

• Human Immunodeficiency Virus (HIV)

• SARS-CoV-2 (COVID-19 related myocarditis)

Viral myocarditis typically begins as a respiratory or gastrointestinal infection, followed by cardiac involvement as the virus invades the myocardium and triggers an immune response.

Bacterial Infections

• Corynebacterium diphtheriae (diphtheritic myocarditis)

• Staphylococcus aureus and Streptococcus species

• Borrelia burgdorferi (Lyme disease)

• Mycoplasma pneumoniae

• Rickettsia species

• Chlamydia psittaci

Protozoal and Parasitic Infections

• Trypanosoma cruzi — causes Chagas disease (common in South America)

• Toxoplasma gondii

• Trichinella spiralis (trichinosis)

Fungal Infections

Occur mainly in immunocompromised individuals, e.g., Candida, Aspergillus, Histoplasma.

2. Non-Infectious Causes

Autoimmune and Immune-Mediated Diseases

• Systemic lupus erythematosus (SLE)

• Rheumatoid arthritis

• Sarcoidosis

• Giant cell myocarditis

• Hypersensitivity (drug-induced) myocarditis

Toxins and Drugs

• Alcohol abuse

• Cocaine

• Chemotherapy agents (doxorubicin, cyclophosphamide)

• Certain antibiotics, anticonvulsants, and anti-inflammatory drugs

Hypersensitivity or Allergic Reactions

Triggered by drugs like penicillin, sulfonamides, or methyldopa, causing eosinophilic infiltration of the myocardium.

Radiation or Physical Injury

Radiation therapy or blunt cardiac trauma may cause localized inflammation.

~Pathophysiology

Myocarditis typically progresses through three main phases:

1. Acute Viral Phase

• The causative virus infects cardiac myocytes.

• The immune system recognizes viral antigens and releases inflammatory cytokines.

• Myocyte necrosis occurs due to direct viral cytotoxicity.

2. Autoimmune (Subacute) Phase

• The immune system may continue attacking cardiac tissue even after viral clearance.

• Autoantibodies against cardiac proteins develop, perpetuating inflammation and tissue damage.

• This phase contributes to chronic myocardial dysfunction.

3. Chronic Phase

• Healing and fibrosis replace damaged myocardium.

• Leads to dilated cardiomyopathy (DCM) and chronic heart failure if extensive.

• Electrical conduction abnormalities may persist.

~Clinical Presentation

The clinical spectrum of myocarditis is extremely broad — from asymptomatic cases to fulminant, life-threatening disease.

Common Symptoms

• Fatigue and malaise

• Chest pain (often mimicking myocardial infarction)

• Palpitations

• Shortness of breath

• Syncope

• Fever and flu-like illness preceding cardiac symptoms

Signs of Heart Failure

• Dyspnea on exertion or at rest

• Orthopnea and paroxysmal nocturnal dyspnea

• Peripheral edema

• Jugular venous distension

• Hepatomegaly

Fulminant Myocarditis

• Rapid onset of severe heart failure or cardiogenic shock

• Hypotension and arrhythmias

• Requires intensive care and mechanical support

~Physical Examination Findings

• Tachycardia disproportionate to fever

• Soft S1 and S3 gallop

• Murmur of mitral or tricuspid regurgitation

• Pericardial rub if perimyocarditis is present

• Signs of left or right heart failure (rales, edema)

~Diagnostic Evaluation

Diagnosis requires a combination of clinical suspicion, imaging, and laboratory investigations.

1. Laboratory Tests

• Cardiac biomarkers (Troponin I, CK-MB): Elevated due to myocyte injury.

• Inflammatory markers: Elevated ESR, CRP.

• Viral serology or PCR: To identify causative virus.

• Autoimmune screening: ANA, rheumatoid factor, etc.

• Complete blood count: May show leukocytosis or eosinophilia (drug-induced type).

2. Electrocardiogram (ECG)

• Non-specific ST-T wave abnormalities.

• Sinus tachycardia.

• Arrhythmias: atrial fibrillation, ventricular tachycardia.

• Conduction defects such as AV block.

3. Chest X-Ray

• Cardiomegaly (enlarged cardiac silhouette).

• Pulmonary congestion or edema in heart failure.

4. Echocardiography

• Most useful non-invasive tool.

• Findings include:

  • Ventricular dilation.

  • Reduced ejection fraction.

  • Wall motion abnormalities.

  • Pericardial effusion (in perimyocarditis).

5. Cardiac Magnetic Resonance Imaging (MRI)

• The gold standard imaging modality for myocarditis.

• Detects inflammation, edema, and fibrosis using T2-weighted imaging and late gadolinium enhancement.

• Helps differentiate myocarditis from ischemic heart disease.

6. Endomyocardial Biopsy (EMB)

• Definitive diagnostic test.

• Histopathological criteria (Dallas criteria):

  • Presence of inflammatory infiltrates with myocyte necrosis not typical of ischemic injury.

• Indicated in:

  • Unexplained new-onset heart failure (<2 weeks).

  • Life-threatening arrhythmias.

  • Suspected giant cell or eosinophilic myocarditis.

~Histopathological Types of Myocarditis

1. Lymphocytic Myocarditis: Most common, typically viral in origin.

2. Eosinophilic Myocarditis: Seen in drug hypersensitivity reactions.

3. Giant Cell Myocarditis: Aggressive, autoimmune type with multinucleated giant cells; poor prognosis.

4. Granulomatous Myocarditis: Associated with sarcoidosis or tuberculosis.

5. Necrotizing Myocarditis: Seen in severe viral infections or toxins.

~Differential Diagnosis

• Acute coronary syndrome (MI)

• Dilated cardiomyopathy

• Pericarditis

• Pulmonary embolism

• Sepsis-related cardiac dysfunction

• Stress (Takotsubo) cardiomyopathy

Differentiation is critical because management strategies differ significantly.

~Management

Management of myocarditis depends on the underlying cause, severity, and presence of heart failure or arrhythmias.

1. General Measures

• Hospitalization for monitoring in moderate to severe cases.

• Bed rest during the acute phase to reduce myocardial workload.

• Avoid competitive sports for at least 3–6 months.

2. Medical Management

a. Supportive Therapy

• Oxygen and ventilatory support if respiratory distress.

• Intravenous fluids cautiously to maintain perfusion without volume overload.

b. Heart Failure Management

• ACE inhibitors / ARBs: Improve ventricular remodeling.

• Beta-blockers: Reduce arrhythmias and improve long-term survival (used once patient stabilizes).

• Diuretics: Relieve pulmonary and systemic congestion.

• Aldosterone antagonists: For chronic heart failure.

• Inotropes (dobutamine, milrinone): In cardiogenic shock.

c. Anti-arrhythmic Therapy

• Amiodarone for ventricular arrhythmias.

• Temporary pacing for advanced AV block.

d. Immunosuppressive Therapy

• Used in autoimmune, giant cell, or eosinophilic myocarditis.

• Corticosteroids (prednisone) ± other immunosuppressants (azathioprine, cyclosporine).

• Not recommended for routine viral myocarditis without biopsy-proven immune etiology.

e. Antiviral or Antimicrobial Therapy

• Only if a specific infectious agent is identified (e.g., antitrypanosomal drugs for T. cruzi).

• No proven benefit of empirical antiviral therapy in viral myocarditis.

3. Advanced and Surgical Management

• Mechanical circulatory support (MCS):

  • Intra-aortic balloon pump (IABP)

  • Extracorporeal membrane oxygenation (ECMO)

  • Left ventricular assist device (LVAD)

• Heart transplantation: Indicated in refractory cases progressing to end-stage heart failure.

~Prognosis

The outcome of myocarditis varies widely:

• Mild cases often recover completely with supportive care.

• Fulminant myocarditis may have high early mortality but better long-term recovery if treated promptly.

• Chronic myocarditis can lead to dilated cardiomyopathy, requiring lifelong treatment.

Prognostic factors:

• Poor: Persistent LV dysfunction, giant cell histology, arrhythmias.

• Favorable: Early diagnosis, mild inflammation, full recovery of function within 6 months.

~Complications

1. Heart Failure: Due to chronic ventricular remodeling.

2. Dilated Cardiomyopathy: End-stage outcome in chronic inflammation.

3. Arrhythmias: Including ventricular tachycardia or fibrillation.

4. Thromboembolism: Due to mural thrombus formation.

5. Sudden Cardiac Death: Particularly in athletes.

~Prevention

• Early treatment of viral infections.

• Avoiding strenuous exercise during viral illness.

• Judicious use of cardiotoxic drugs and alcohol.

• Vaccination against common viruses (e.g., influenza, COVID-19).

• Screening of high-risk patients with autoimmune or systemic diseases.

~Recent Advances

1. Cardiac MRI has revolutionized non-invasive diagnosis and follow-up.

2. Biomarker Research: New biomarkers like high-sensitivity troponin and BNP improve early detection.

3. Immunomodulatory Therapy: Experimental agents targeting specific cytokines (e.g., IL-1 blockers) show promise.

4. Gene and viral sequencing help identify novel pathogens.

5. mRNA vaccine–related myocarditis: Identified as rare, mild, and self-limiting; under continuous surveillance.

~Myocarditis and COVID-19

The SARS-CoV-2 virus has renewed global focus on myocarditis. It can occur as:

• Direct viral invasion of myocardium.

• Post-viral immune reaction (Multisystem Inflammatory Syndrome).

• Vaccine-associated myocarditis — rare, usually mild, and resolves with conservative treatment.

Clinical features often include chest pain, elevated troponin, and ECG changes mimicking MI, but coronary arteries are normal. Most patients recover fully with supportive care.

~Rehabilitation and Follow-Up

After recovery:

• Avoid competitive sports for at least 3–6 months.

• Gradual return to activity once left ventricular function normalizes.

• Regular follow-up with echocardiography and ECG.

• Counseling on lifestyle, medication adherence, and risk factor control.

~Conclusion

Myocarditis is a multifaceted inflammatory disease of the heart muscle with diverse causes, presentations, and outcomes. Its unpredictable course ranges from silent infection to life-threatening heart failure and arrhythmia. Modern diagnostic tools — especially cardiac MRI and biopsy — allow earlier detection and tailored management.

Prompt recognition, supportive therapy, and targeted treatment of underlying causes can lead to complete recovery in most cases. Continued research into immunologic and genetic mechanisms holds promise for better prevention and precision-based therapy in the future.