Giant cell myocarditis

Abstract

Giant cell myocarditis (GCM) usually affects previously healthy adults and is a rapidly progressive and frequently fatal disease. It has a median survival of 3 months to death or transplant without appropriate therapy. Hence, early diagnosis is critical, with evidence showing rapidly instituted cyclosporine-based immunosuppression can improve transplant-free survival. Although transplant is an effective strategy, GCM can recur in 25% of transplanted hearts. We present a case of GCM in a patient who presented with conduction abnormalities and fulminant heart failure.

Giant cell myocarditis (GCM) is a rapidly progressive, fatal disorder that accounts for approximately 17% of myocarditis fatalities. The myocardium is often infiltrated by lymphocytes and giant cells that cause diffuse fibrosis, leading to fatal arrhythmias and systolic dysfunction.

CASE PRESENTATION

A 56-year-old man presented with 1 week of exertional dyspnea and lightheadedness. On presentation, his blood pressure was 130/80 mm Hg and his heart rate was 69 beats/minute. An electrocardiogram revealed a first-degree atrioventricular block with a left bundle branch block, whereas an electrocardiogram from a year earlier did not reveal any abnormalities. An echocardiogram demonstrated a 55% ejection fraction with no wall motion abnormalities; a nuclear stress test demonstrated a basal inferior perfusion defect; and coronary angiography showed normal coronary arteries. He was discharged home with a Holter monitor. The patient presented with similar symptoms a week later. The electrocardiogram was notable for a third-degree heart block and a right bundle branch block. Given his alternating bundle branch blocks, a dual-chamber pacemaker was implanted. However, in the following 2 months, the patient continued to have worsening dyspnea. Echocardiography showed a 20% ejection fraction with akinesis of the inferolateral wall and diffuse left ventricular hypokinesis. Pacemaker interrogation did not reveal any arrhythmias. Laboratory investigations were notable for an elevated troponin of 8.49 ng/mL, high-sensitivity C-reactive protein of 26.5 mg/L, and normal erythrocyte sedimentation rate. An infectious and autoimmune workup was negative. Subsequent cardiac magnetic resonance imaging (cMRI) showed a nondiagnostic delayed gadolinium enhancement. Subsequently, endomyocardial biopsy showed nonspecific focal lymphocytic infiltrates in the myocardium. Given the high suspicion of GCM, he was started on high-dose steroids and tacrolimus. The patient developed cardiogenic shock requiring placement of a ventricular assist device. When analyzing the excised core of the apex for cannula placement, granulomatous myocarditis with giant cell formation was seen (Figure 1).

Figure 1.

Nonspecific focal lymphocytic infiltrate in myocarditis with giant cell formation (arrow).

DISCUSSION

GCM is a frequently fatal disorder with an incidence of 0.007%, as reported in an extensive Japanese autopsy registry comprising 377,841 cases from 1958 to 1977.¹ However, this number might underestimate the true incidence, as autopsy is not routinely performed in all cases. The pathogenesis of this disease is yet to be elucidated but is often attributed to T lymphocyte–mediated inflammation of the cardiac muscle. It is characterized by the presence of necrosis with multinucleated giant cells.² Numerous reports suggest an association with lymphoma, sarcoma, thymoma, and various autoimmune or inflammatory conditions.³ The clinical course is characterized by progressive heart failure with refractory ventricular arrhythmias or atrioventricular blocks. Infrequently, it may present as myocardial infarction or sudden death.^4,5 Endomyocardial biopsy is the gold standard for diagnosis, whereas cMRI and positron electron tomography help identify sites for biopsy. Repeat endomyocardial biopsy may be needed, as the involvement is patchy.⁶

Management involves the use of immunosuppressive agents and heart transplantation. Given the rarity of the condition and paucity of clinical data, there have not been any randomized controlled trials to guide management; however, several observational studies have shown that early institution of cyclosporine-based combined therapy improves clinical outcomes.⁴ Animal models also support the use of immunosuppressive therapy. Autoimmunization of an experimental rat with myosin leads to GCM in the rat characterized by a myocardial infiltrate with CD4+ cells that produce tumor necrosis factor and nitric oxide.^7,8 It was also shown that immunotherapy against T lymphocytes prevents the progression of GCM.⁹

The median transplant-free survival in patients in a multicenter registry was shown to be 11.5 months with azathioprine and corticosteroids; 12.5 months with cyclosporine in combination with other agents; 3 months with no immunosuppressive agents; and 3.8 months with corticosteroids alone.⁴ Long-term immunosuppressive treatment is vital, as there is a risk of recurrence on discontinuing or tapering the treatment.¹⁰ Even with appropriate therapy, patients remain at risk for fatal arrhythmias. These patients frequently need bridging to transplantation with mechanical devices such as extracorporeal membrane oxygenation or a ventricular assist device.¹¹ Although transplantation is considered the definitive treatment, there have been reports of recurrence in 25% of patients.^4,11

This case reveals the progressive nature of GCM, which has a median survival of 3 months to death or transplant without appropriate therapy. With immunotherapy, the 5-year survival rate free of transplant is between 52% and 72%. It is crucial to consider GCM in cardiomyopathy of unknown etiology. Early institution of treatment may prevent catastrophic outcomes.