Idiopathic giant cell myocarditis or cardiac sarcoidosis? A retrospective audit of a nationwide case series

Abstract

Aims Cardiac sarcoidosis (CS) and giant cell myocarditis (GCM) are inflammatory cardiomyopathies sharing histopathological and clinical features. Their differentiation is difficult and susceptible of confusion and apparent mistakes. The possibility that they represent different phenotypes of a single disease has been debated. Methods and resultsWe made a retrospective audit of 73 cases of GCM diagnosed in Finland since the late 1980s. All available histological material was reanalyzed as were other examinations pertinent to the distinction between GCM and CS. Finding granulomas in or outside the heart was considered diagnostic of CS and exclusive of GCM. Altogether 45 of the 73 cases of GCM (62%) were reclassified as CS. In all except one case, this was based on finding sarcoid granulomas that either had been originally missed (n = 29) or misinterpreted (n = 11) or were found in additional posttransplant myocardial specimens (n = 3) or samples of extracardiac tissue (n = 1) accrued over the disease course. Supporting the reclassification, patients relocated to the CS group had less heart failure at presentation (prevalence 20% vs. 46%, P = 0.017) and better 1 year transplant-free survival (82% vs. 45%, P = 0.011) than patients considered to represent true GCM. Conclusions Recognizing granulomas in or outside the heart remains a challenge for the pathologist. Given that CS and GCM are considered distinct diseases and granulomas exclusive of GCM, many cases of GCM, if thoroughly scrutinized, may need reclassification as CS. However, whether CS and GCM are truly different entities or parts of a one-disease continuum has not yet been conclusively settled.

Long‐term outcome and its predictors in giant cell myocarditis. Letter regarding the article ‘Long‐term outcome and its predictors in giant cell myocarditis’

“…This forced us to re-evaluate all GCM diagnoses made since 1991 in our country. 2 Altogether 26 of the 46 cases were reclassified as CS, most commonly due to recognition, with help of immunochemistry, of sarcoid granulomas missed or misinterpreted on original microscopy ( Figure 1). The 5-year estimate (95% confidence interval) of transplant-free survival, having been 42% (39-56%) in our 2016 report, 1 was 25% (0-40%) in the 20 patients keeping the GCM diagnosis.…”

“…It did not include recent significant evidence such as the study reporting that the risk of cardiac dysfunction over 4 years is two-fold higher when high-sensitivity troponin T (hs-TnT) is >14 ng/L at the end of anthracycline treatment and that a doubling of N-terminal fragment of pro-B-type NP during therapy is associated with a 1.6-fold higher risk of cardiac dysfunction. 2 Similarly, the Authors did not consider a novel and promising field of research, namely troponins as indicators of myocarditis by immune checkpoint inhibitors. 3 Furthermore, the whole analysis revolved around a comparison between normal and elevated troponin levels, but we are not entirely convinced of the opportunity to pool together troponin T and I assays of different generations, with highly different upper reference values (e.g.…”

Recurrent Syncope Due to Concurrent Cardiac Sarcoidosis and Large-Vessel Vasculitis

“…Few reports have described sarcoidosis with inflammatory large-vessel disease [ 6 – 8 ], and it remains unclear if these 2 diseases are related. Although they have been considered 2 separate diseases [ 9 ], there is also histopathologic evidence more recently that they may be a continuum of a single disease state rather than separate entities, especially in the case of giant cell myocarditis [ 10 ]. Previously, it was noted in these patients that the diagnosis of sarcoidosis preceded the vasculitis, often by several years [ 8 ].…”

Rebuttal From Drs Kupari and Lehtonen

“…The suppression of physiological 18 F-FDG uptake in the cardiac muscle is a key factor in optimizing diagnostic accuracy. 9 Inadequate preparation can lead to falsepositive 18 F-FDG PET scans. A variety of preparation protocols have been used, usually with prolonged fasting of at least 12 hours with fatty rich and low-carbohydrate meals the day before, and North American guidelines have been recently published.…”

“…Whether they are genuinely different disease entities, or different phenotypes of a single T cellmediated inflammatory cardiomyopathy, is still discussed. 9 In the latter scenario, giant cell myocarditis represents fulminant isolated CS.…”