Diagnosis, Treatment, and Outcome of Giant-Cell Myocarditis in the Era of Combined Immunosuppression

Abstract

G iant-cell myocarditis (GCM) is known as a rare, rapidly progressive, and frequently fatal myocardial disease in young and middle-aged adults. It is attributed to a T lymphocyte-mediated inflammation of the heart muscle and associates with systemic autoimmune diseases in ≈20% of cases. 1,2The most common early manifestations are heart failure, ventricular arrhythmias, and atrioventricular block, but GCM may also disguise as an acute myocardial infarction and rarely presents as an unexpected sudden cardiac death.1-3 The diagnosis of GCM rests fully on microscopy of the heart muscle and even in experienced centers >4 in 10 cases may escape detection until autopsy or cardiac transplantation. Aside from nonspecific measures to combat its symptomatic manifestations, the treatment of GCM relies on immunosuppression. Retrospective observations from the Multicenter GCM Registry 1,4 and a small prospective study with repeat biopsies 5 suggest that cyclosporine-based combined immunosuppression may be able to reduce myocardial inflammation 5 and improve clinical outcome. 1,4,5 Yet, these data are uncontrolled and suffer from lack of details about the treatments given 1,4 and the possibility of survivor bias. 1,4,5 The key problem is that the rarity and seriousness of GCM make controlled treatment trials, let alone use of a placebo arm, virtually impossible. The only such attempt, a cooperative endeavor by 17 centers, was terminated after 6 years because of difficulties in recruiting patients.5 Therefore, carefully studied observational patient series continue to add to the knowledge about GCM. We report here our experience in 32 patients with GCM, of whom 26 received combined immunosuppression. We focus on the diagnosis of GCM and on the outcome of patients with contemporary treatment. Our key observations suggest that repeat and imaging-guided biopsies increase the detection rate of GCM and that combined immunosuppression supported by therapy for heart failure and arrhythmias may result in transplant-free survival in two thirds of patients. Clinical Perspective on p 22 Methods PatientsFrom the year 1991 through 2011, 32 patients with histologically verified GCM were seen at the Division of Cardiology, Helsinki University Central Hospital. The majority of diagnoses (29/32) were made after year 2000, that is, during the latter half of the study period. The medical records, laboratory test, imaging studies, and available biopsy material of all patients were retrospectively reviewed and © 2012 American Heart Association, Inc. Background-Giant-cell myocarditis often escapes diagnosis until autopsy or transplantation and has defied proper treatment trials for its rarity and deadly behavior. Current therapy rests on multiple-drug immunosuppression but its prognostic influence remains poorly known. We set out to analyze (1) our experience in diagnosing giant-cell myocarditis and (2) the outcome of patients on combined immunosuppression. Methods and Results-We reviewed the histories, diagnostic procedures, details of treatment, a...

Giant cell myocarditis masquerading as orbital myositis with a rapid, fulminant course necessitating mechanical support and heart transplantation

“…Diagnosis relies on high clinical suspicion and biopsy‐proven evidence of giant cells within cardiac tissue with a cautious realization of the high rate of false‐negative biopsy results (sensitivity 68% with single biopsy) 8. Imaging such as cardiac MRI or 18FDG‐PET with SPECT imaging may aide in localization of inflammatory infiltration resulting in targeted biopsies 8.…”

“…Imaging such as cardiac MRI or 18FDG‐PET with SPECT imaging may aide in localization of inflammatory infiltration resulting in targeted biopsies 8. Treatment requires a multimodality approach with pharmacologic interventions and mechanical support devices.…”

“…Survival without treatment is dismal with a rate of death or cardiac transplantation of 89% and a medial survival of about 5.5 months from symptom onset 5. With combination immunosuppressive agents, survival without need for transplant is drastically improved with a 1 year survival of 77–80% and a 5 year survival of 58% 6, 8. However, most studies have shown that the majority of patients ultimately require transplantation or permanent ventricular support 9.…”

“…For this reason, timely referral to centres with a heart failure service and capability of advanced heart failure support is essential. Importantly, recurrence in the transplanted heart is also reported and warrants close follow‐up and routine biopsies 5, 8…”

A STEMI gone viral

“…high-dose steroids and cyclosporine) which has been shown to improve transplant-free survival. [10] It should be noted that these and other potential causes of myocarditis occur at the cellular level, which in turn can only be detected by EMB.…”