Clozapine-induced hypersensitivity myocarditis presenting as sudden cardiac death
Natraj Katta, Sudarshan Balla, Kul Aggarwal
Abstract
Hypersensitivity myocarditis is a rare but serious adverse effect of clozapine, a commonly used psychiatric drug. We report the case of sudden cardiac death from clozapine-induced hypersensitivity myocarditis diagnosed at autopsy. A 54-year-old Caucasian male on clozapine therapy for bipolar disorder presented with a sudden onset of shortness of breath. Laboratory studies were significant for elevated N-terminal prohormone of brain natriuretic peptide. During his hospital stay, the patient died of sudden cardiac arrest from ventricular tachycardia. The autopsy revealed hypersensitivity myocarditis, which usually occurs in the first 4 weeks after the initiation of clozapine. A 4-week monitoring protocol, including laboratory assessment of troponin and C-reactive protein, may assist in the early diagnosis of this potentially fatal condition.
Keywords
References
1. Asenjo Lobos C, Komossa K, Rummel-Kluge C, et al. Clozapine versus other atypical antipsychotics for schizophrenia. Cochrane Database Syst Rev. 2010;(11):Cd006633. PMid:21069690.
2. Kant R, Chalansani R, Chengappa KN, Dieringer MF. The off-label use of clozapine in adolescents with bipolar disorder, intermittent explosive disorder, or posttraumatic stress disorder. J Child Adolesc Psychopharmacol. 2004;14(1):57-63. PMid:15142392. http://dx.doi.org/10.1089/104454604773840490.
3. Miller DD. Review and management of clozapine side effects. J Clin Psychiatry. 2000;61(Suppl 8):14-7. PMid:10811238.
4. Haas SJ, Hill R, Krum H, et al. Clozapine-associated myocarditis: a review of 116 cases of suspected myocarditis associated with the use of clozapine in Australia during 1993-2003. Drug Saf. 2007;30(1):47-57. PMid:17194170. http://dx.doi.org/10.2165/00002018-200730010-00005.
5. Kilian JG, Kerr K, Lawrence C, Celermajer DS. Myocarditis and cardiomyopathy associated with clozapine. Lancet. 1999;354(9193):1841-5. PMid:10584719. http://dx.doi.org/10.1016/S0140-6736(99)10385-4.
6. Reinders J, Parsonage W, Lange D, Potter JM, Plever S. Clozapine-related myocarditis and cardiomyopathy in an Australian metropolitan psychiatric service. Aust N Z J Psychiatry. 2004;38(11-12):915-22. PMid:15555025. http://dx.doi.org/10.1080/j.1440-1614.2004.01481.x.
7. Ronaldson KJ, Fitzgerald PB, McNeil JJ. Clozapine-induced myocarditis, a widely overlooked adverse reaction. Acta Psychiatr Scand. 2015;132(4):231-40. PMid:25865238. http://dx.doi.org/10.1111/acps.12416.
8. Hatton JL, Bhat PK, Gandhi S. Clozapine-induced myocarditis: recognizing a potentially fatal adverse reaction. Tex Heart Inst J. 2015;42(2):155-7. PMid:25873829. http://dx.doi.org/10.14503/THIJ-13-3633.
9. Park Y, Ahn SG, Ko A, et al. Hypersensitivity myocarditis confirmed by cardiac magnetic resonance imaging and endomyocardial biopsy. Korean J Intern Med. 2014;29(2):236-40. PMid:24648808. http://dx.doi.org/10.3904/kjim.2014.29.2.236.
10. Pieroni M, Cavallaro R, Chimenti C, Smeraldi E, Frustaci A. CLozapine-induced hypersensitivity myocarditis*. Chest. 2004;126(5):1703-5. PMid:15539749. http://dx.doi.org/10.1378/chest.126.5.1703.
11. Gerald J, Berry KAA. In Myocardiits: from Bench to Bedside. 2nd ed. Totowa: Humana Press; 2003. p. 325-70.
12. Ben m’rad M, Leclerc-Mercier S, Blanche P, et al. Drug-induced hypersensitivity syndrome: clinical and biologic disease patterns in 24 patients. Medicine. 2009;88(3):131-40. PMid:19440116. http://dx.doi.org/10.1097/MD.0b013e3181a4d1a1.
13. Pursnani A, Yee H, Slater W, Sarswat N. Hypersensitivity myocarditis associated with azithromycin exposure. Ann Intern Med. 2009;150(3):225-6. PMid:19189924. http://dx.doi.org/10.7326/0003-4819-150-3-200902030-00027.
14. Taliercio CP, Olney BA, Lie JT. Myocarditis related to drug hypersensitivity. Mayo Clin Proc. 1985;60(7):463-8. PMid:4010343. http://dx.doi.org/10.1016/S0025-6196(12)60870-2.
15. Magnani JW, Dec GW. Myocarditis: current trends in diagnosis and treatment. Circulation. 2006;113(6):876-90. PMid:16476862. http://dx.doi.org/10.1161/CIRCULATIONAHA.105.584532.
16. Takkenberg JJ, Czer LS, Fishbein MC, et al. Eosinophilic myocarditis in patients awaiting heart transplantation. Crit Care Med. 2004;32(3):714-21. PMid:15090952. http://dx.doi.org/10.1097/01.CCM.0000114818.58877.06.
17. Hägg S, Spigset O, BAHons AB, Söderström TG. Myocarditis related to clozapine treatment. J Clin Psychopharmacol. 2001;21(4):382-8. PMid:11476122. http://dx.doi.org/10.1097/00004714-200108000-00005.
18. Ronaldson KJ, Fitzgerald PB, Taylor AJ, Topliss DJ, McNeil JJ. A new monitoring protocol for clozapine-induced myocarditis based on an analysis of 75 cases and 94 controls. Aust N Z J Psychiatry. 2011;45(6):458-65. PMid:21524186. http://dx.doi.org/10.3109/00048674.2011.572852.
19. Cohen H, Loewenthal U, Matar M, Kotler M. Association of autonomic dysfunction and clozapine. Heart rate variability and risk for sudden death in patients with schizophrenia on long-term psychotropic medication. Br J Psychiatry. 2001;179(2):167-71. PMid:11483480. http://dx.doi.org/10.1192/bjp.179.2.167.
20. Wang JF, Min JY, Hampton TG, et al. Clozapine-induced myocarditis: role of catecholamines in a murine model. Eur J Pharmacol. 2008;592(1-3):123-7. PMid:18627770. http://dx.doi.org/10.1016/j.ejphar.2008.06.088.
21. Abdel-Aty H, Boye P, Zagrosek A, et al. Diagnostic performance of cardiovascular magnetic resonance in patients with suspected acute myocarditis: comparison of different approaches. J Am Coll Cardiol. 2005;45(11):1815-22. PMid:15936612. http://dx.doi.org/10.1016/j.jacc.2004.11.069.
22. Mahrholdt H, Goedecke C, Wagner A, et al. Cardiovascular magnetic resonance assessment of human myocarditis: a comparison to histology and molecular pathology. Circulation. 2004;109(10):1250-8. PMid:14993139. http://dx.doi.org/10.1161/01.CIR.0000118493.13323.81.
23. Laser JA, Fowles RE, Mason JW. Endomyocardial biopsy. Cardiovasc Clin. 1985;15(1):141-63. PMid:3916087.
24. Cooper LT, Baughman KL, Feldman AM, et al. The Role of Endomyocardial Biopsy in the Management of Cardiovascular DiseaseA Scientific Statement From the American Heart Association, the American College of Cardiology, and the European Society of Cardiology Endorsed by the Heart Failure Society of America and the Heart Failure Association of the European Society of Cardiology. J Am Coll Cardiol. 2007;50(19):1914-31. PMid:17980265. http://dx.doi.org/10.1016/j.jacc.2007.09.008.
25. Yanagisawa T, Inomata T, Watanabe I, et al. Clinical significance of corticosteroid therapy for eosinophilic myocarditis. Int Heart J. 2011;52(2):110-3. PMid:21483171. http://dx.doi.org/10.1536/ihj.52.110.
26. Kim CH, Vlietstra RE, Edwards WD, Reeder GS, Gleich GJ. Steroid-responsive eosinophilic myocarditis: diagnosis by endomyocardial biopsy. Am J Cardiol. 1984;53(10):1472-3. PMid:6720598. http://dx.doi.org/10.1016/S0002-9149(84)91473-5.
27. Watanabe N, Nakagawa S, Fukunaga T, Fukuoka S, Hatakeyama K, Hayashi T. Acute necrotizing eosinophilic myocarditis successfully treated by high dose methylprednisolone. Jpn Circ J. 2001;65(10):923-6. PMid:11665801. http://dx.doi.org/10.1253/jcj.65.923.
28. Zaacks SM, Klein L, Tan CD, Rodriguez ER, Leikin JB, Leikin J. Hypersensitivity myocarditis associated with ephedra use. J Toxicol Clin Toxicol. 1999;37(4):485-9. PMid:10465246. http://dx.doi.org/10.1081/CLT-100102440.
29. Aggarwal A, Bergin P, Jessup P, Kaye D. Hypersensitivity myocarditis presenting as cardiogenic shock. J Heart Lung Transplant. 2001;20(11):1241-4. PMid:11704488. http://dx.doi.org/10.1016/S1053-2498(01)00313-8.
Publication date:
12/12/2016