Case Presentation

Girish Rambaran
PGY3
01/11/2019
CASE
• 72yo Female
• CC: SOB for 4 Months
• HPI: Patient presented with progressively worsening dyspnea on exertion
for the past 4 months. Now unable to walk to bathroom. NYHA IV. PND+,
Orthopnea has to sleep upright. Also with bilateral lower limb swelling
(Right > left). Denies chest pains nor palpitations. Admits to low grade fever
and night sweats. No new athralgias nor myalgias
• PMH: Rheumatoid Arthritis for 40 years, Giant cell arteritis for 10 years
(Large segment involvement of Subclavian Arteries). No CAD nor risk
factors for CAD. Diagnosed with RLL DVT 1 wk ago
• DHx: Apixaban 5mg BD(1wk), Prednisolone 10mg OD, HCQ 200mg BD
CASE
• O/E: Patient seen sitting upright. No obvious distress. Afebrile
• Unable to get arm BP by ausculatation (Chronic issue attributed to SC
GCA), HR 80 and regular, RR 20, SPO2 95% RA
• JVP up to jaw while upright
• Lungs with fine crackles to both bases
• CVS: Displaced PMI+. S1S2Mo. S3+
• Abd: benign
• EXT: bilateral pitting edema, RLL 3+, LLL 2+
Investigations
• CBC: Normal
• RFT normal
• LFT: SGOT/SGPT in 200s
• CRP: 89mg/ml (Normal <1)
• ECG: Sinus rhythm, Left axis deviation, LBBB
• ECHO: Severe global systolic dysfunction, LVEF 11%. Mild pulmonary
HTN
• NB: Previous ECHO in 2014 with Preserved EF 55-60%
 Giant Cell Myocarditis
• Rare and frequently fatal type of myocarditis
• Clinical course in GCM is usually characterized by acute or fulminant deterioration
in left ventricular systolic function despite standard HF treatment, frequent
ventricular arrhythmias, and heart block.
• Mean age of onset: 42 +/- 12 years. No gender predominance
• Considered Idiopathic and mediated by T-Lymphocytes.
• Despite being a relatively infrequent cause of myocarditis overall, GCM has been
reported to account for approximately 17% of all myocarditis fatalities.
• Median transplant-free survival time from 3.0 to 12.3 months
 Diagnosis
• High Clinical suspicion
• Cardiac MRI : Late-gadolinium enhancement in affected areas as well as Cine-
MRI and myocardial strain.
• Not specific for GCM, although atypical for viral myocarditis
• LGE may narrow DDx to GCM vs Cardiac sarcoidosis
• Endomysial Biopsy (EMB)- Gold Standard test
• If performed soon after the onset of symptoms, the sensitivity of EMB for GCM ranges from
68% to 80%.
• Classic histopathologic features are prominent myocyte necrosis associated with a
multifocal or diffuse inflammatory cell infiltrate composed of abundant T lymphocytes,
multinucleated giant cells, plasma cells, easily identified eosinophils, and occasional
neutrophils
 Cardiac MRI and autopsy examination
findings. A, T2-weighted images showed high-
intensity signals in the septum and
inferoseptal wall at the base (arrows). B, Late-
gadolinium enhancement (LGE) was detected
in the transmural inferoseptal and inferior left
ventricular (LV) wall and the subendocardial
anterolateral LV wall at the base
(arrowheads). C, At autopsy, macroscopic
examination of the base of the left ventricle
showed transmural fibrotic changes in the
inferoseptal and inferior LV wall and in the
subendocardial anterolateral LV wall. D and E,
Microscopic examination showed
multinucleated giant cells on the right
ventricular side of the septum at the
presumed site of the biopsy, and extensive
lymphocytic infiltration without giant cells in
the lateral LV wall (hematoxylin and eosin
staining; original magnification: D, ×20; E,
×40. F, Masson trichrome staining showed
fibrotic foci.
Morphologic features of giant cell
myocarditis.
A, Multifocal serpiginous inflammatory
infiltrate.
B, The infiltrate is composed of
lymphocytes, eosinophils, plasma cells,
and prominent multinucleated giant
cells. Discrete granulomas are not
evident.
C, There is extensive myocyte necrosis
associated with giant cell infiltrate
(hematoxylin-eosin, original
magnifications ×4 [A] and ×40 [B and C]).
 Treatment
• Standard HF management (ACEi+BB+MRA+Diuretics) usually yields poor
prognosis without immunosuppressive therapy
• With appropriate immunosuppressive therapy, the 5-year survival rate free of
transplant ranges from 52% to 72%
• Optimal immunosuppressive regimen remains to be defined
• Combined double- or triple-drug cyclosporine-based therapy reportedly leads to
a partial clinical remission in two-thirds of patients
• Immunosuppression must be continued long term as GCM can recur up to 8
years after diagnosis if immunosuppressive therapy is tapered or terminated
• Patients remain at risk of developing ventricular arrhythmias and may require
implantable cardioverter-defibrillators
• Ultimately, many patients still require heart transplantation.
• Idiopathic giant-cell myocarditis--natural history and treatment.
Multicenter Giant Cell Myocarditis Study Group Investigators. Cooper
LT Jr, Berry GJ, Shabetai R. N Engl J Med. 1997;336(26):1860
• Among 22 patients treated with immunosuppressive medications that
included cyclosporine, the average transplant-free survival was 13
months compared with only three months among 30 patients who
did not receive therapy
• Usefulness of immunosuppression for giant cell myocarditis. Cooper LT
Jr, Hare JM, Tazelaar HD, Edwards WD, Starling RC, Deng MC, Menon
S, Mullen GM, Jaski B, Bailey KR, Cunningham MW, Dec GW, Giant Cell
Myocarditis Treatment Trial Investigators.Am J Cardiol.
2008;102(11):1535. Epub 2008 Sep 18.
Prospective uncontrolled study of 11 patients with GCM who were
treated with one year of cyclosporine and glucocorticoids; nine patients
also received 7 to 10 days of muromonab-CD3. Among the 11 patients,
there was only one death and two transplantations during one-year
follow-up.
• Diagnosis, treatment, and outcome of giant-cell myocarditis in the era
of combined immunosuppression. Kandolin R, Lehtonen J, Salmenkivi
K, Räisänen-Sokolowski A, Lommi J, Kupari M. Circ Heart Fail. 2013
Jan;6(1):15-22. Epub 2012 Nov 13.
• Study of 32 patients with GCM, including 26 patients treated with
combined immunosuppression (two to four drugs; including
cyclosporine in 20 patients) [35]. Among the 26 patients treated with
immunosuppression, the Kaplan-Meier estimate of transplant-free
survival from diagnosis was 77 percent at one year, 63 percent at two
years, and 63 percent at five years.
 References
• Jin Xu and Erin G. Brooks (2016) Giant Cell Myocarditis: A Brief Review. Archives of Pathology
& Laboratory Medicine: December 2016, Vol. 140, No. 12, pp. 1429-1434.
• Cooper LT, Berry GJ, Shabetai R. Idiopathic giant-cell myocarditis–natural history and
treatment. Multicenter Giant Cell Myocarditis Study Group Investigators.N Engl J
Med. 1997; 336:1860–1866
• Yasumori Sujino, Fumiko Kimura, Jun Tanno, Shintaro Nakano, Eriko Yamaguchi, Michio
Shimizu, Nanami Okano, Yuichi Tamura, Jun Fujita, Leslie T. Cooper, Takaaki Senbonmatsu,
Toshihiro Muramatsu, and Shigeyuki Nishimura. Cardiac Magnetic Resonance Imaging in
Giant Cell Myocarditis : Intriguing Associations With Clinical and Pathological Features
• Cooper LT Jr, Hare JM, Tazelaar HD, et al. Usefulness of immunosuppression for giant cell
myocarditis. Am J Cardiol 2008; 102:1535.
• Litovsky SH, Burke AP, Virmani R. Giant cell myocarditis: an entity distinct from sarcoidosis
characterized by multiphasic myocyte destruction by cytotoxic T cells and histiocytic giant
cells. Mod Pathol 1996; 9:1126.
• Menghini VV, Savcenko V, Olson LJ, et al. Combined immunosuppression for the treatment of
idiopathic giant cell myocarditis. Mayo Clin Proc 1999; 74:1221.