Usefulness of immunosuppression for giant cell myocarditis

Leslie T Cooper Jr, Joshua M Hare, Henry D Tazelaar, William D Edwards, Randall C Starling, Mario C Deng, Santosh Menon, G Martin Mullen, Brian Jaski, Kent R Bailey, Madeleine W Cunningham, G William Dec, Giant Cell Myocarditis Treatment Trial Investigators, Leslie T Cooper Jr, Santosh Menon, Mario Deng, G Martin Mullin, Randall Starling, Brian Jaski, Robert Bourge, G Wiliam Dec, Joshua Hare, Andrew Kao, Carl Leier, Lynne Wagoner, Marl Zucker, Hal Skopecki, Srinivas Murali, Joe Mendez, Alida Caforio, Richard Rodeheffer, Jay W Mason, Karla V Ballman, Bernard J Gersh, Henry D Tazelaar, William D Edwards, Leslie T Cooper Jr, Joshua M Hare, Henry D Tazelaar, William D Edwards, Randall C Starling, Mario C Deng, Santosh Menon, G Martin Mullen, Brian Jaski, Kent R Bailey, Madeleine W Cunningham, G William Dec, Giant Cell Myocarditis Treatment Trial Investigators, Leslie T Cooper Jr, Santosh Menon, Mario Deng, G Martin Mullin, Randall Starling, Brian Jaski, Robert Bourge, G Wiliam Dec, Joshua Hare, Andrew Kao, Carl Leier, Lynne Wagoner, Marl Zucker, Hal Skopecki, Srinivas Murali, Joe Mendez, Alida Caforio, Richard Rodeheffer, Jay W Mason, Karla V Ballman, Bernard J Gersh, Henry D Tazelaar, William D Edwards

Abstract

Giant cell myocarditis (GCM) is a rare and highly lethal disorder. The only multicenter case series with treatment data lacked cardiac function assessments and had a retrospective design. We conducted a prospective, multicenter study of immunosuppression including cyclosporine and steroids for acute, microscopically-confirmed GCM. From June 1999 to June 2005 in a standard protocol, 11 subjects received high dose steroids and cyclosporine, and 9 subjects received muromonab-CD3. In these, 7 of 11 were women, the mean age was 60 +/- 15 years, and the mean time from symptom onset to presentation was 27 +/- 33 days. During 1 year of treatment, 1 subject died of respiratory complications on day 178, and 2 subjects received heart transplantations on days 2 and 27, respectively. Serial endomyocardial biopsies revealed that after 4 weeks of treatment the degree of necrosis, cellular inflammation, and giant cells decreased (p = 0.001). One patient who completed the trial subsequently died of a fatal GCM recurrence after withdrawal of immunosuppression. Her case demonstrates for the first time that there is a risk of recurrent, sometimes fatal, GCM after cessation of immunosuppression. In conclusion, this prospective study of immunosuppression for GCM confirms retrospective case reports that such therapy improves long-term survival. Additionally, withdrawal of immunosuppression can be associated with fatal GCM recurrence.

Trial registration: ClinicalTrials.gov NCT00027443.

Conflict of interest statement

Disclosures: None of the Authors have any conflicts of interest to disclose.

Figures

Figure 1
Figure 1
Average histologic scores by blinded analysis at baseline and day 30 in subjects enrolled in the GCM Treatment Trial.* p†p=0.43, ‡p=0.01
Figure 2
Figure 2
Representative histologic findings of widespread inflammatory infiltrate including giant cells at baseline (2a) is largely resolved with some replacement fibrosis after 30 days of therapy (2b). Hematoxylin and Eosin 100x.
Figure 2
Figure 2
Representative histologic findings of widespread inflammatory infiltrate including giant cells at baseline (2a) is largely resolved with some replacement fibrosis after 30 days of therapy (2b). Hematoxylin and Eosin 100x.
Figure 3
Figure 3
Change in ejection fraction for 10 subjects with baseline and 30 day assessments. p=NS

Source: PubMed

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