What is the recommended diagnostic work‑up and management for giant‑cell myocarditis in a previously healthy 20‑50‑year‑old adult presenting with acute heart‑failure symptoms, ventricular arrhythmias, or high‑grade atrioventricular block?

Giant Cell Myocarditis: Diagnostic Work-Up and Management

Immediate Diagnostic Approach

Endomyocardial biopsy (EMB) must be performed urgently in any previously healthy young adult presenting with new-onset heart failure of less than 2 weeks duration combined with hemodynamic compromise, ventricular arrhythmias, or high-grade AV block, as this clinical constellation strongly suggests giant cell myocarditis—a rapidly fatal condition with median transplant-free survival of only 5.5 months without treatment. 1

When to Perform EMB (Class I Recommendation)

• Unexplained heart failure <2 weeks duration with normal-sized or dilated left ventricle AND hemodynamic compromise 1
• Heart failure 2 weeks to 3 months duration with dilated LV AND any of: 1
  • New ventricular arrhythmias
  • Mobitz type II second-degree or third-degree AV block
  • Failure to respond to standard heart failure therapy within 1-2 weeks

Critical Clinical Clues for GCM

Giant cell myocarditis presents with higher rates of specific features compared to lymphocytic myocarditis: 1

• Ventricular tachycardia at presentation: 15% of cases (29% develop it during follow-up)
• Complete heart block at presentation: 5% of cases (15% develop it during follow-up)
• Acute coronary syndrome presentation: 6% of cases
• Association with autoimmune disorders, thymoma, or drug hypersensitivity

EMB Technique and Sensitivity

Repeat biopsies are frequently necessary—sensitivity increases from 68% with initial biopsy to 93% after up to 2 repeat procedures. 2 The diagnosis requires histologic confirmation showing multinucleated giant cells in inflammatory lesions. 1, 3

Cardiac MRI Findings

While EMB remains the gold standard, CMR can support the diagnosis: 1

• Large areas of high signal intensity in various, sometimes atypically subendocardial layers
• Widespread yet nonischemic necrosis pattern in acute cases
• Similar appearance to severe forms of cardiac sarcoidosis
• CMR's primary value is confirming widespread nonischemic necrosis to guide urgency of EMB

Immediate Management Strategy

Hemodynamic Support

Aggressive mechanical circulatory support (percutaneous cardiopulmonary support or ECMO) must be initiated immediately if cardiogenic shock does not reverse rapidly with inotropes, or if refractory VT/VF occurs. 1, 4 This is the cornerstone of GCM management with clear survival benefit. 5

• Start dopamine 5 mcg/kg/min, titrate up to 20-50 mcg/kg/min based on response 4
• Initiate mechanical support if VT/VF refractory to 3-5 defibrillation attempts 1
• Transfer immediately to center with advanced heart failure and MCS capabilities 4

Arrhythmia Management

All patients require: 1, 6

• Mandatory hospitalization with prolonged continuous ECG monitoring
• Temporary pacemaker insertion for symptomatic heart block or if high-grade AV block triggers ventricular tachyarrhythmias
• Consider earlier ICD implantation compared to other myocarditis types given adverse prognosis 1
• If persistent AV block develops, permanent pacing is required—device selection must account for LV dysfunction severity and prognosis 1

Immunosuppressive Therapy

Rapid initiation of methylprednisolone has immediate effect on reducing myocardial inflammation and must be started as soon as GCM is diagnosed. 5 This represents a paradigm shift in management. 7

Cyclosporine-based combination immunosuppression (2-4 drugs) dramatically improves outcomes: 1, 2

• Median transplant-free survival increases from 3.0 months without immunosuppression to 12.3 months with cyclosporine-based therapy (P=0.003) 1
• Contemporary data shows 69% transplant-free survival at 1 year, 58% at 2 years, and 52% at 5 years with combined immunosuppression 2
• Treatment must be sustained long-term with optimal heart failure medications for myocardial recovery 5

Heart Failure Medical Therapy

Once hemodynamically stable: 4

• ACE inhibitors: Start low dose (captopril 1-6.25 mg) if systolic BP >100 mmHg
• Beta-blockers: Only if hemodynamically stable; avoid in overt heart failure with pulmonary congestion or low output

Transplantation Considerations

Evaluate for cardiac transplantation early—mean interval from diagnosis to death or transplant is 6 months. 8 Patients with GCM respond well to transplantation, though recurrence in the graft occurs in approximately 18-25% of cases (2 of 8 transplanted patients in one series). 8

At 4 years, only 11% of GCM patients are alive without transplantation, compared to 44% with lymphocytic myocarditis, underscoring the aggressive nature of this disease. 1

Critical Pitfalls to Avoid

• Delaying EMB while pursuing non-invasive testing—time is critical as median survival without treatment is 3 months 1
• Single negative EMB ruling out GCM—repeat biopsies increase sensitivity to 93% 2
• Withholding immunosuppression pending "definitive" diagnosis—if clinical suspicion is high and EMB shows inflammation, start therapy immediately 5
• Underestimating ongoing arrhythmia risk—59% of transplant-free survivors experience sustained ventricular tachyarrhythmias during follow-up despite clinical remission 2
• Selecting biventricular assist device without pathological diagnosis—GCM has high likelihood of progressive right ventricular failure requiring biventricular support 1

Long-Term Monitoring

Even with successful immunosuppression achieving partial clinical remission, patients remain prone to ventricular tachyarrhythmias requiring ongoing monitoring and consideration of ICD therapy. 2 Two-thirds of patients reach freedom from severe heart failure and transplantation need, but continuing arrhythmia vigilance is mandatory.