David F. Miranda, Mosi K. Bennett, and Peter Zimbwa (2017) Acute Fulminant Giant Cell Myocarditis Presenting with Syncopal Events Treated Successfully with Orthotopic Heart Transplant. Journal of the Minneapolis Heart Institute Foundation: January 2017, Vol. 1, No. 1, pp. 72-75.
David F. Miranda, MD*†, Mosi K. Bennett, MD, PhD*, and Peter Zimbwa, MD, PhD, MSc, MRCP, DTM&H†
*Minneapolis Heart Institute, Abbott Northwestern Hospital, Minneapolis, MN;
†Division of Cardiology, Department of Medicine, Hennepin County Medical Center, Minneapolis, MN
Address for correspondence:
Peter Zimbwa, MD, PhD, MSC, MRCP, DTM&H
800 East 28th Street
Abbott Northwestern Hospital
Minneapolis, MN 55407
Myocarditis is a major cause of end-stage heart failure and is responsible for up to 10% of cases of idiopathic dilated cardiomyopathy. Giant cell myocarditis is a particularly fulminant disease that has a poor response to immunosuppressive therapy. Cardiac transplantation is the definitive treatment.
Keywords: heart transplantation, giant cell myocarditis, immunosuppression, multimodality imaging, heart transplantation rejection
Giant cell myocarditis is a rare form of myocarditis of unknown origin and is characterized histologically by diffuse myocardial necrosis with multinucleated giant cells with the absence of sarcoidosis.1 Patients often present with rapid progressive clinical heart failure and ventricular arrhythmias.2 Overall, the median survival of patients with giant cell myocarditis is 5.5 months from the onset of symptoms. Because of rapid disease progression, some die waiting for a heart transplant. In a registry of 34 patients who received heart transplants, 9 had recurrence of giant cell myocarditis in their transplanted heart and 1 died.3,4 Patient outcome can be improved with early recognition and subsequent intervention with immunosuppressive therapy and advanced heart failure therapy.
A 56-year-old male presented to the emergency department with several presyncopal episodes. He had been experiencing these episodes associated with palpitations for 2 weeks. Initial electrocardiogram showed first degree atrioventricular (AV) block with right bundle branch morphology and ST depression with reciprocal ST elevation in aVR concerning for global ischemia (Figure 1). His blood pressure was 127/68 and his heart rate was 86 beats per minute. His cardiovascular exam was unremarkable. Initial laboratory values were as follows: hemoglobin of 15 g/dL, platelets of 206,000/cu, sodium of 136 mmol/L, potassium of 4.2 mmol/L, and creatinine 0.89 mg/dL. Initial troponin I was 3.887 ng/mL. A coronary angiogram showed no obstructive coronary artery disease. An echocardiogram performed 6 days prior to presentation showed no wall motion abnormalities with a normal ejection fraction. A cardiac magnetic resonance image (MRI) showed extensive gadolinium uptake in portions of the epicardium and endocardium of the left ventricle, right ventricle, and interventricular septum (Figure 2) and was suspicious for myocarditis. Extensive viral serology for acute myocarditis was unremarkable. An endomyocardial biopsy showed no clear evidence of inflammation or infiltrative disease. He then had progressive conduction disease abnormalities with frequent pauses (up to 6 seconds) and type Mobitz type II AV block.
Cardiac MRI was done that showed extensive myocarditis, including the left ventricle, the right ventricle, and the interventricular septum.
Two weeks after discharge, he represented with sustained monomorphic ventricular tachycardia. Repeat endomyocardial biopsy showed giant cell myocarditis (Figure 3). At this time, he was started on prednisone and cyclosporine. He was listed on the United Network for Organ Sharing (UNOS) as a status 2 for heart transplantation and a dual chamber implantable cardioverter defibrillator was placed for primary prevention. He was subsequently readmitted to the hospital with progressive fatigue and ongoing palpitations. Despite aggressive antiarrhythmic and immunosuppressant therapy, he had persistent waxing and waning ejection fraction and arrhythmias. He was upgraded to UNOS status 1Ae and had an orthotropic heart transplantation 74 days after his initial presentation. Pathological examination of the explanted heart revealed residual lymphocytic myocarditis with focal as well as mild rare giant cells (Figure 4). There was interstitial replacement with fibrosis as well as lymphocytic infiltrates (Figure 5). Clinically, he is doing very well three years post-transplantation, is able to exercise, and lives a normal life.
A, B. Examples of giant cells in the endomyocardium. C. Shows focus of inflammation with a giant cell in the periphery. D. Evidence of active inflammation invading normal myocardial cells.
Explanted heart pathology with residual lymphocytic myocarditis, with focal as well as mild rare giant cells.
Interstitial replacement with fibrosis of the endomyocardium.
Giant cell myocarditis is characterized pathologically by a mixed inflammatory cell infiltrate with necrotic myocytes, multinucleated giant cells with histiocytes surrounded by eosinophils, lymphocytes, and occasional plasma cells. Giant cell myocarditis may be an autoimmune disorder dependent on CD-4 positive lymphocytes.5 It is important to have an interpretation of biopsy specimens or of explanted heart specimens with full knowledge of the patient’s clinical history. It is often necessary to examine multiple levels within the endomyocardial biopsy to discover granulomas that may be focal. This may be why his initial biopsy was negative.
Treatment of patients with giant cell myocarditis has never been studied in a randomized control fashion. The first reported case of successful treatment with aggressive immunosuppression was in 1987.6 Since this time, a few patients with giant cell myocarditis have responded to immunosuppression, but the Giant Cell Myocarditis Registry has shown the most success with heart transplantation performed in more than 50% of patients.2 Also, there have been reported cases of recurrence in the transplanted hearts.
Currently, heart transplantation is the gold standard therapy with median survival exceeding 10 years for patients with end-stage heart failure.7 Many advancements in the fields of immunosuppression, infection prophylaxis, and surgical techniques have transformed heart transplantation into a routine treatment.8
In conclusion, patients with giant cell myocarditis often present with acute heart failure and arrhythmias and conduction abnormalities. Despite the initial relative hemodynamic stability, our patient had an early recurrence of intractable symptomatic arrhythmias refractory to usual therapy. He developed a clear indication for heart transplantation, with an excellent outcome.9
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