Giant Cell Myocarditis

Introduction:

Giant cell myocarditis (GCM) is a rare cardiovascular disorder characterized by inflammation of the myocardium (heart muscles), resulting in myocarditis. The cause has been pinned as idiopathic, but the overall nature has been quite fatal due to no evident cure. Myocarditis has often been seen in heart-transplant patients with a prior diagnosis of conduction abnormalities and heart failure. GCM has been closely associated with other systemic autoimmune conditions in 20 % of the cases.

Who Is Susceptible to Giant Cell Myocarditis?

Giant cell myocarditis is a rare disorder with about 0.13 diagnoses in 100,000 individuals with no apparent gender dominance. The condition may develop at any age throughout life, but the majority of the cases belong to the young or middle-aged groups with a median age of 42. To date, around 300 cases have been recorded in the medical literature.

What Causes Giant Cell Myocarditis?

The exact cause of giant cell myocarditis remains a mystery, but the close association with other autoimmune disorders suggests an autoimmune role in developing giant cell myocarditis. Giant cell myocarditis has been observed to be associated with conditions such as inflammatory bowel diseases (like Crohn’s disease) and also with thymoma (a tumor of the thymus). About 20 % of GCM cases are associated with autoimmune conditions. GCM may also occur due to drug hypersensitivity reactions or infections from parvovirus B19 or coxsackie B2 virus.

What Are the Signs and Symptoms of Giant Cell Myocarditis?

The initial symptoms of the condition (rapid onset) are:

• Ankle swelling.

• Chest pain.

• Heart palpitations.

• Dyspnea (shortness of breath).

• Arrhythmia (irregular heartbeats).

• Tachycardia (fast heart rate) or bradycardia (slow heart rate).

• Lightheadedness.

• Syncope (loss of consciousness).

• Extreme fatigue.

• Ventricular arrhythmias.

• Heart block (first, second, and third degree).

How to Diagnose Giant Cell Myocarditis?

The primary diagnosis is based on recognizing the developing clinical symptoms as presented to the clinician. The clinical features are suggestive of cardiovascular disease. Further investigations are required to confirm a giant cell myocarditis diagnosis. The confirmatory diagnosis is made with a biopsy in which a tissue sample obtained from the heart is sent to an expert cardiac pathologist for analysis.

Heart muscle biopsy is a risky procedure as it carries certain complications like pericardial effusion (fluid accumulation within the pericardium), cardiac tamponade (pressure in the heart due to fluid buildup around the organ), or ventricular wall puncture. To obtain a myocardial sample, the surgeon accesses the blood vessel by a catheter through the neck. Imaging guidance is used to steer the catheter to the heart, where a special tool obtains a piece of cardiac tissue. The patient may require more than one biopsy as GCM may partially affect the myocardium, leaving the rest parts healthy. MRI (magnetic resonance imaging) may be done to determine the region of the specimen collection.

Other tests to exclude any other cardiac disorders are EKG (electrocardiogram), echocardiogram, and cardiac catheterization. Blood tests can also be ordered to check for various cardiac disorders. Infectious etiology may be diagnosed via cardiac DNA polymerase chain reaction.

What Are the Histological Findings of Giant Cell Myocarditis?

Histopathological studies of a cardiac tissue sample show:

• Myocyte degeneration.

• Edema.

• Nuclear size variation.

• Lymphocytic infiltration.

• Eosinophils.

• Macrophages.

• Non-necrotizing granulomas.

• Macrophage-derived KP-1 positive giant cells.

• Myocytic necrosis.

• Granulation tissue.

• KP-1-negative myogenic giant cells.

• CD8 cells.

• CD4 cells.

• Cytotoxic T cells.

• Macrophagic giant cells.

• Fibrosis.

How to Treat Giant Cell Myocarditis?

Standard management protocols outline supportive care against cardiac failure and arrhythmias. The patient may require a pacemaker, catheter ablation, left ventricular assist device, or implantable heart defibrillator (implantable cardioverter defibrillator). The doctor can prescribe medications to reduce inflammation and prevent rhythm abnormalities. Drugs like Cyclosporine, Prednisone, and Azathioprine are prescribed to suppress the immune system. These drugs can present with certain side effects like muscle pain, headache, hyperglycemia, hypertension, diarrhea, and sleeping disorders. The last stage of treatment requires a heart transplant. Unresponsive immunosuppression therapy may be provided with mechanical circulatory support devices such as extracorporeal membrane oxygenation or ventricular assist devices that can act as bridges to recovery or transplant.

What Is the Prognosis of Giant Cell Myocarditis?

Giant cell myocarditis is a fatal condition and may rapidly progress to heart failure or heart block. If the patient qualifies, they may require a heart transplant within five months. Post-transplant, the patient’s survivability is approximately 71 % at a five-year follow-up, even with 25 % giant cell infiltration into the donor’s heart. The recurrence may occur between three weeks to nine years after the transplant, with an average recurrence time of about one month. The life of the donor’s heart is better, which may be resultant of post-transplant immunosuppressive therapy.

Long-term immunosuppressive therapy can extend the life span by 20 years, even without any transplant procedure.

What Is the Differential Diagnosis of Giant Cell Myocarditis?

• Cardiac sarcoidosis.

• Lymphocytic myocarditis.

• Hypersensitivity myocarditis.

What Are the Complications of Giant Cell Myocarditis?

The most common complications of giant cell myocarditis are:

• Heart failure.

• Heart block.

• Ventricular arrhythmias.

• Atrioventricular block.

The most common complications arising from long-term immunosuppressive therapy are:

• Hyperglycemia.

• Superimposed or opportunistic infections.

• Renal dysfunctions.

• Malignancies.

Conclusion:

Giant cell myocarditis is a fatal disorder. Even with medications, the patient may require a heart transplant as soon as five months from diagnosis. Transplant, which by itself, is a treatment that is difficult to qualify for. At the same time, long-term pharmacotherapy carries severe side effects. The patients need intense care to prevent potential cardiac shortcomings. The condition may be easily misdiagnosed if not for biopsy and histopathological examination. If misdiagnosed as any other cardiac condition, the treatment for the misdiagnosed condition can cloud the GCM features, which may worsen the actual condition.