Accepted Manuscript Acute Necrotizing Eosinophilic Myocarditis in a Patient Taking Garcinia Cambogia Extract Successfully Treated with High-Dose Corticosteroids Scott F. Allen, MD Robert W. Godley, MD Joshua M. Evron, MD Amer Heider, MD John M. Nicklas, MD Michael P. Thomas, MD PII:

S0828-282X(14)01293-8

DOI:

10.1016/j.cjca.2014.08.025

Reference:

CJCA 1387

To appear in:

Canadian Journal of Cardiology

Received Date: 20 May 2014 Revised Date:

13 August 2014

Accepted Date: 13 August 2014

Please cite this article as: Allen SF, Godley RW, Evron JM, Heider A, Nicklas JM, Thomas MP, Acute Necrotizing Eosinophilic Myocarditis in a Patient Taking Garcinia Cambogia Extract Successfully Treated with High-Dose Corticosteroids, Canadian Journal of Cardiology (2014), doi: 10.1016/ j.cjca.2014.08.025. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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Acute Necrotizing Eosinophilic Myocarditis in a Patient Taking Garcinia Cambogia Extract Successfully Treated with High-Dose Corticosteroids

First Author: Scott F. Allen, MD

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Authors’ Names (in order of authorship): Scott F. Allen, MD1 Robert W. Godley, MD2 Joshua M. Evron, MD2 Amer Heider, MD3 John M. Nicklas, MD1 Michael P. Thomas, MD1

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Short Title: Acute Necrotizing Eosinophilic Myocarditis

Word Count: 1021

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Email: [email protected] Phone: 888-287-1082 Fax: 734-615-3326

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Correspondance: Scott F. Allen, MD 1500 E. Medical Center Drive Frankel Cardiovascular Center SPC 5853 Attn: Jill Griswold Ann Arbor, MI 48109

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Affiliations: 1University of Michigan Health System, Department of Cardiovascular Medicine; 2 University of Michigan Health System, Department of Internal Medicine; 3University of Michigan Health System, Department of Pathology

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Subject Code: [16] Myocardial cardiomyopathy disease Key Words: Eosinophilic myocarditis, necrotizing eosinophilic myocarditis, myocarditis, garcinia cambogia

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ABSTRACT A previously healthy 48-year-old female was evaluated for lightheadedness and chest heaviness 2 weeks after starting the herbal supplement Garcinia cambogia. She was found to be hypotensive and had an

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elevated serum troponin level. The patient had a progressive clinical decline, ultimately developing fulminant heart failure and sustained ventricular arrhythmias, which required ECMO support.

Endomyocardial biopsy was consistent with acute necrotizing eosinophilic myocarditis. High-dose

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corticosteroids were initiated promptly and her condition rapidly improved, with almost complete cardiac recovery one week later. In conclusion, we have described a case of acute necrotizing

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eosinophilic myocarditis associated with use of Garcinia cambogia extract.

ACCEPTED MANUSCRIPT SUMMARY A 48-year-old female presented with non-specific symptoms and an elevated serum troponin. She was found to have fulminant heart failure caused by acute necrotizing eosinophilic myocarditis. She

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required temporary ECMO support but was successfully treated with high-dose corticosteroids and had

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complete recovery of cardiac function.

ACCEPTED MANUSCRIPT CASE PRESENTATION A 48-year-old female with no past medical history presented with symptoms of lightheadedness, chest heaviness, and a pre-syncopal event on the morning of admission. She denied any other preceding

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symptoms including fever, rash, arthralgias, diarrhea, cough, or dyspnea. She was not prescribed any medications, but had recently started taking the popular weight-loss supplement Garcinia cambogia extract 2.5 weeks before. On exam, the patient was afebrile with a blood pressure of 90/62 and a HR of 96. 12-lead EKG showed sinus rhythm with low QRS voltage and T-wave inversions in the inferior

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leads, and the initial troponin was 2.61 ng/ml. She was admitted for further management.

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Initial echocardiogram showed normal LV and RV size and function. Labs were unremarkable and there was no peripheral eosinophilia. An extensive infectious workup - including testing for HIV, parvovirus, CMV, group A streptococcus, malaria, chlamydia, leptospira, viral hepatitis, respiratory viruses, urine cultures, and blood cultures - was as unrevealing. Coronary angiography the day after her admission revealed angiographically normal coronary arteries. On hospital day 4 the troponin peaked at

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11.4 ng/ml, she developed diffuse ST-segment elevations on EKG, and a repeat echocardiogram showed moderate to severe LV and RV systolic dysfunction. She was sent for endomyocardial biopsy, then transferred to the cardiac ICU. Several hours later she suddenly developed a sustained monomorphic

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ventricular tachycardia and, despite successful defibrillation, remained pulseless. CPR was performed

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until she could be cannulated for emergency bedside veno-arterial ECMO. Shortly after her arrest, the endomyocardial biopsy results returned revealing diffuse myocardial inflammation with eosinophil prominence and extensive myocardial necrosis – consistent with acute necrotizing eosinophilic myocarditis (ANEM). She was quickly given 1g of IV methylprednisolone. This was continued daily for 3 days, decreased to 1mg/kg daily for 7 days, and then converted to oral prednisone and slowly tapered on a weekly basis for 6 weeks, at which time the prednisone was discontinued. Interestingly, the patient never developed peripheral eosinophilia, nor did she develop any other eosinophilia-related

ACCEPTED MANUSCRIPT disorders like colitis, esophagitis, or asthma. Serum troponin levels returned to an undetectable level by hospital day 20. Despite early complications, including acute kidney injury requiring continuous renal

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replacement therapy, the patient survived and stabilized quickly within 24 hours. Her LV and RV function improved rapidly and she was successfully decannulated from ECMO after 5 days. At this time her LV and RV were not dilated, her LVEF had returned to normal, and her RV had only mild systolic dysfunction. She was extubated several days later and was neurologically intact. The patient was seen

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in the outpatient cardiology clinic 3 months following her initial presentation. At that time she had

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recovered completely from her myocarditis with normal LV and RV systolic function and no signs or symptoms of heart failure. She had no neurologic deficits and her kidney function had returned to normal. DISCUSSION

Garcinia cambogia is a pumpkin-like fruit that is found in Southeast Asia and Western Africa.

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The active ingredient in the widely popular weight-loss supplement, hydroxycitric acid, is extracted from the rind of the fruit. Its reported effects include inhibition of fatty acid synthesis and increasing serotonin levels in the brain.1 Few adverse effects have been reported with the supplement to date.1,2

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While we cannot definitively prove that Garcinia cambogia extract was the cause of the patient’s

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myocarditis, it seems probable given the temporal relationship, lack of any other precipitating factors, and the known association of eosinophilic myocarditis with several medications and herbal supplements. To our knowledge, this is the first reported case of ANEM associated with Garcinia cambogia extract. Patients and physicians should be cautioned until more is known about the adverse effects of this supplement Because ANEM is a rare and often fatal disease, large trials comparing therapies and management are not available. When high-dose corticosteroids are initiated early, a number of case reports have shown favorable outcomes, and often complete cardiac recovery.3 Other

ACCEPTED MANUSCRIPT immunosuppressants have been used successfully in conjunction with corticosteroids including azathioprine (2mg/kg/day) and IVIG.4,5 To our knowledge, there are no examples in the literature of successful treatment with a steroid-sparing regimen. While there are no guidelines regarding dosing or

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length of steroid therapy, we elected to use high-dose IV methylprednisolone (1g/day) initially for 3 days, aiming to drastically reducing myocardial inflammation and prevent myocyte necrosis. We empirically used a slowly tapering dose of oral prednisone, starting at 1mg/kg/day, over the following 6 weeks as this dosing strategy has been used successfully in other case reports in the literature. Since the

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patient had stopped taking Garcinia cambogia extract, which we believed to be the cause of her ANEM,

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we did not feel that a longer course of immunosuppressive therapy was warranted. There are no cases reported in the literature of recurrent ANEM secondary to medications or herbal supplements when the triggering agent has been removed. Overall, our case supports the use of early high-dose corticosteroids as an effective therapy for ANEM, with our patient showing dramatic improvement within 24 hours and almost complete cardiac recovery after 5 days.

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CONCLUSIONS

This case demonstrates a potentially new association between the popular weight-loss supplement Garcinia cambogia extract and ANEM, and serves as an example of the utility of high-dose

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corticosteroids in the early treatment of this frequently fatal disease.

ACCEPTED MANUSCRIPT REFERENCES 1. Chuah LO, Yeap SK, Ho WY, Beh BK, Alitheen NB. In vitro and in vivo toxicity of garcinia or hydroxycitric acid: a review. Evidence-Based Complementary and Alternative Medicine. 2012; 2012: 1-12.

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2. Mansi IA, Huang J. Rhabdomyolysis in response to weight-loss herbal medicine. Am J Med Sci. 2004; 327(6):356-7. 3. Galiuto L, Enriquez-Sarano M, Reeder GS, Tazelaar HD, Li JT, Miller FA Jr, Gleich GJ. Eosinophilic myocarditis manifesting as myocardial infarction: early diagnosis and successuful treatment. Mayo Clin Proc. 1997; 72(7):603-610.

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4. Aggarwal A, Bergin P, Jessup P, Kaye D. Hypersensitivity myocarditis presenting as cardiogenic shock. J Heart Lung Transplant. 2001; 20(11):1241-1244.

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5. Chau E, Chow W, Chiu C, Wang E. Treatment and outcome of biopsy-proven fulminant myocarditis in adults. Int J Cardiol. 2006; 110(3):405-406.

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Figure: Endomyocardial biopsy specimen, stained with hematoxylin and eosin, under low magnification (a) showing severe myocardial inflammation with extensive necrosis. High magnification (b) showing a mixed inflammatory infiltrate of lymphocytes, histiocytes, and a prominent number of

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eosinophils (arrows).

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Video 1 – Parasternal long-axis view 4 hours before the patient’s VT arrest showing severe LV

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systolic dysfunction with severe global hypokinesis as well as significant RV systolic dysfunction.

Video 2 – Parasternal long-axis view 7 weeks after treatment with corticosteroids showing normal

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LV and RV systolic function.

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ACCEPTED MANUSCRIPT

Acute necrotizing eosinophilic myocarditis in a patient taking Garcinia cambogia extract successfully treated with high-dose corticosteroids.

A previously healthy 48-year-old woman was evaluated for lightheadedness and chest heaviness 2 weeks after starting the herbal supplement Garcinia cam...
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