心肌炎的主要治疗为支持疗法和常规心力衰竭治疗。[32]Hunt SA, Abraham WT, Chin MH, et al. ACC/AHA 2005 Guideline update for the diagnosis and management of chronic heart failure in the adult. Circulation. 2005 Sep 20;112(12):e154-235.http://circ.ahajournals.org/content/112/12/e154.fullhttp://www.ncbi.nlm.nih.gov/pubmed/16160202?tool=bestpractice.com[43]Howlett JG, McKelvie RS, Arnold JM, et al. Canadian Cardiovascular Society Consensus Conference guidelines on heart failure, update 2009: diagnosis and management of right-sided heart failure, myocarditis, device therapy and recent important clinical trials. Can J Cardiol. 2009 Feb;25(2):85-105.http://www.ccs.ca/images/Guidelines/Guidelines_POS_Library/HF_CC_2009.pdfhttp://www.ncbi.nlm.nih.gov/pubmed/19214293?tool=bestpractice.com 扩张型心肌病与心肌炎可能有很大重叠;在进行了心内膜心肌活检的急性扩张型心肌病患者中,高达 16% 的患者患有活检确诊的心肌炎。[38]Felker GM, Thompson RE, Hare JM, et al. Underlying causes and long-term survival in patients with initially unexplained cardiomyopathy. N Engl J Med. 2000 Apr 13;342(15):1077-84.http://www.ncbi.nlm.nih.gov/pubmed/10760308?tool=bestpractice.com 因此,治疗目标为管理并发心肌病的心肌病和心肌炎患者。不推荐常规使用免疫抑制剂治疗心肌炎患者。[12]Heart Failure Society of America. Myocarditis: current treatment: HFSA 2010 comprehensive heart failure practice guideline. J Card Fail. 2010 Jun;16(6):e176-9.http://www.onlinejcf.com/article/S1071-9164%2810%2900231-9/fulltext
终末器官灌注不足或心源性休克
少部分急性心肌炎患者将出现暴发性心力衰竭或心源性休克,需要有创性血流动力学监测及积极的药物治疗。可以插入肺动脉导管,以帮助优化心脏充盈压及进行心血管治疗的快速滴定。可包括血管加压药(例如去甲肾上腺素)或正性肌力药(例如多巴酚丁胺)。[44]Mills RM, Hobbs RE. Drug treatment of patients with decompensated heart failure. Am J Cardiovasc Drugs. 2001;1(2):119-25.http://www.ncbi.nlm.nih.gov/pubmed/14728041?tool=bestpractice.com 在极少数情况下,需要机械辅助装置作为恢复的过渡,治疗无效的患者则需要接受心脏移植。[45]Farrar DJ, Holman WR, McBride LR, et al. Long-term follow-up of Thoratec ventricular assist device bridge-to-recovery patients successfully removed from support after recovery of ventricular function. J Heart Lung Transplant. 2002 May;21(5):516-21.http://www.ncbi.nlm.nih.gov/pubmed/11983540?tool=bestpractice.com
左心室收缩功能不全:支持疗法和常规心力衰竭治疗
应尽早开始给予血管紧张素转换酶抑制剂 (ACEI) 或血管紧张素II受体拮抗剂 (ARB)。急性和慢性情况下均可使用利尿剂和血管扩张药,目标为优化心脏内充盈压并增加心输出量。
ACEI或ARB:
动物研究显示,肾素-血管紧张素拮抗剂能够有效治疗慢性心力衰竭,而且在急性心肌炎的早期给予肾素-血管紧张素拮抗剂,可提高病人生存率并抑制其进展为扩张型心肌病。[46]Yamamoto K, Shioi T, Uchiyama K, et al. Attenuation of virus-induced myocardial injury by inhibition of the angiotensin II type 1 receptor signal and decreased nuclear factor-kappa B activation in knockout mice. J Am Coll Cardiol. 2003 Dec 3;42(11):2000-6.http://www.ncbi.nlm.nih.gov/pubmed/14662266?tool=bestpractice.com
血管扩张药:
口服动脉血管扩张药(肼苯哒嗪)和静脉血管扩张药(硝酸盐)可迅速提高心输出量,并降低肺部和左心室充盈压。[44]Mills RM, Hobbs RE. Drug treatment of patients with decompensated heart failure. Am J Cardiovasc Drugs. 2001;1(2):119-25.http://www.ncbi.nlm.nih.gov/pubmed/14728041?tool=bestpractice.com 此外,在采用此联合疗法的慢性心力衰竭患者中亦观察到生存获益。[32]Hunt SA, Abraham WT, Chin MH, et al. ACC/AHA 2005 Guideline update for the diagnosis and management of chronic heart failure in the adult. Circulation. 2005 Sep 20;112(12):e154-235.http://circ.ahajournals.org/content/112/12/e154.fullhttp://www.ncbi.nlm.nih.gov/pubmed/16160202?tool=bestpractice.com
β受体阻滞剂:
同样,应在患者不再处于急性失代偿性心力衰竭后开始β受体阻滞剂治疗
在急性心肌炎的动物模型中,显示及早开始 β 受体阻滞剂治疗可减轻心肌炎症。[47]Wang JF, Meissner A, Malek S, et al. Propranolol ameliorates and epinephrine exacerbates progression of acute and chronic viral myocarditis. Am J Physiol Heart Circ Physiol. 2005 Oct;289(4):H1577-83.http://ajpheart.physiology.org/cgi/content/full/289/4/H1577http://www.ncbi.nlm.nih.gov/pubmed/15923319?tool=bestpractice.com[48]Pauschinger M, Rutschow S, Chandrasekharan K, et al. Carvedilol improves left ventricular function in murine coxsackievirus-induced acute myocarditis association with reduced myocardial interleukin-1beta and MMP-8 expression and a modulated immune response. Eur J Heart Fail. 2005 Jun;7(4):444-52.http://www.ncbi.nlm.nih.gov/pubmed/15921778?tool=bestpractice.com
醛固酮拮抗剂:
纽约心脏协会 III 级或 IV 级心力衰竭患者应开始给予醛固酮拮抗剂。[32]Hunt SA, Abraham WT, Chin MH, et al. ACC/AHA 2005 Guideline update for the diagnosis and management of chronic heart failure in the adult. Circulation. 2005 Sep 20;112(12):e154-235.http://circ.ahajournals.org/content/112/12/e154.fullhttp://www.ncbi.nlm.nih.gov/pubmed/16160202?tool=bestpractice.com
利尿剂治疗:
免疫抑制疗法和注射用免疫球蛋白(IVIG)
由于与心肌炎相关的长期心肌改变,似乎是由细胞免疫和体液免疫异常激活介导的,因此推测免疫抑制为有效的治疗形式。尽管有这样的理论依据,用免疫抑制减弱心肌炎患者炎症反应的试验结果总体上令人失望。[12]Heart Failure Society of America. Myocarditis: current treatment: HFSA 2010 comprehensive heart failure practice guideline. J Card Fail. 2010 Jun;16(6):e176-9.http://www.onlinejcf.com/article/S1071-9164%2810%2900231-9/fulltext 精心设计的前瞻性随机对照试验 (RCT) 使用皮质类固醇联合或不联合环孢菌素或硫唑嘌呤对活检确诊的心肌炎进行免疫抑制治疗,结果显示,左心室射血分数 (LVEF) 未出现长期改善,且无生存获益。[49]Parrillo JE, Cunnion RE, Epstein SE, et al. A prospective, randomized, controlled trial of prednisone for dilated cardiomyopathy. N Engl J Med. 1989 Oct 19;321(16):1061-8.http://www.ncbi.nlm.nih.gov/pubmed/2677721?tool=bestpractice.com[50]Mason JW, O'Connell JB, Herskowitz A, et al. A clinical trial of immunosuppressive therapy for myocarditis. The Myocarditis Treatment Trial Investigators. N Engl J Med. 1995 Aug 3;333(5):269-75.http://www.nejm.org/doi/full/10.1056/NEJM199508033330501#t=articlehttp://www.ncbi.nlm.nih.gov/pubmed/7596370?tool=bestpractice.com左心室射血分数(LVEF)改善:有中等质量证据表明,在急性心肌炎伴左心室功能不全患者中,与安慰剂相比,免疫疗法在第28周时并未导致左心室射血分数的提高。[46]Yamamoto K, Shioi T, Uchiyama K, et al. Attenuation of virus-induced myocardial injury by inhibition of the angiotensin II type 1 receptor signal and decreased nuclear factor-kappa B activation in knockout mice. J Am Coll Cardiol. 2003 Dec 3;42(11):2000-6.http://www.ncbi.nlm.nih.gov/pubmed/14662266?tool=bestpractice.com受试者<200名的随机对照临床试验(RCT)、受试者>200名且方法学存在缺陷的随机对照临床试验(RCT)、方法学存在缺陷的系统评价或者高质量的观察性(队列)研究。 同样地,在数项小规模研究中,对使用静脉注射免疫球蛋白 (IVIG) 治疗急性心肌炎进行了评估。对新诊断为急性扩张型心肌病的患者进行的一项随机对照临床试验发现,与标准疗法相比,接受静脉注射免疫球蛋白 (IVIG) 治疗的患者无死亡率获益或左心室射血分数 (LVEF) 改善。[51]McNamara DM, Holubkov R, Starling RC, et al. Controlled trial of intravenous immune globulin in recent-onset dilated cardiomyopathy. Circulation. 2001 May 8;103(18):2254-9.http://circ.ahajournals.org/content/103/18/2254.fullhttp://www.ncbi.nlm.nih.gov/pubmed/11342473?tool=bestpractice.com死亡率或病情改善:有中等质量证据表明,在近期发生的扩张型心肌病患者中,随后6个月或12个月的随访发现:与安慰剂疗法相比,静脉内免疫球蛋白疗法并无益处。[47]Wang JF, Meissner A, Malek S, et al. Propranolol ameliorates and epinephrine exacerbates progression of acute and chronic viral myocarditis. Am J Physiol Heart Circ Physiol. 2005 Oct;289(4):H1577-83.http://ajpheart.physiology.org/cgi/content/full/289/4/H1577http://www.ncbi.nlm.nih.gov/pubmed/15923319?tool=bestpractice.com受试者<200名的随机对照临床试验(RCT)、受试者>200名且方法学存在缺陷的随机对照临床试验(RCT)、方法学存在缺陷的系统评价或者高质量的观察性(队列)研究。 活检确诊的心肌炎患者亦无该获益。这些数据表明,不能推荐使用标准免疫抑制方案常规治疗心肌炎。应根据具体情况逐一做出是否使用免疫抑制方案的决定。此外,巨细胞心肌炎或继发于自身免疫性疾病的心肌炎患者除外;研究显示,这两组患者均可获益于积极的早期免疫抑制治疗。[4]Dec GW. Introduction to clinical myocarditis. In: Cooper LT, ed. Myocarditis: from bench to bedside. Totowa, NJ: Humana Press; 2003:257-281.[52]Cooper LT Jr, Berry GJ, Shabetai R; Multicenter Giant Cell Myocarditis Study Group Investigators. Idiopathic giant-cell myocarditis - natural history and treatment. N Engl J Med. 1997 Jun 26;336(26):1860-6.http://www.nejm.org/doi/full/10.1056/NEJM199706263362603#t=articlehttp://www.ncbi.nlm.nih.gov/pubmed/9197214?tool=bestpractice.com
针对心肌炎的特定病因的治疗
淋巴细胞性(病毒性)心肌炎
淋巴细胞性心肌炎主要采用支持疗法和标准心力衰竭疗法进行治疗。如同心肌炎的所有病因,出现暴发性心力衰竭和心源性休克的患者可能需要有创性血流动力学监测、积极的静脉用利尿剂或正性肌力药治疗、甚至机械性血流动力学支持设备。由于恢复率高,建议进行积极治疗,尤其是在病程的早期。
在大多数情况下,免疫抑制疗法对病毒性心肌炎无效。[53]Chen HS, Wang W, Wu SN, et al. Corticosteroids for viral myocarditis. Cochrane Database Syst Rev. 2013 Oct 18;(10):CD004471.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD004471.pub3/fullhttp://www.ncbi.nlm.nih.gov/pubmed/24136037?tool=bestpractice.com [
]What are the effects of corticosteroids in people with viral myocarditis?https://cochranelibrary.com/cca/doi/10.1002/cca.843/full显示答案 静脉注射丙种球蛋白是否有效仍不确定。[54]Robinson J, Hartling L, Vandermeer B, et al. Intravenous immunoglobulin for presumed viral myocarditis in children and adults. Cochrane Database Syst Rev. 2015 May 20;(5):CD004370.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD004370.pub3/fullhttp://www.ncbi.nlm.nih.gov/pubmed/25992494?tool=bestpractice.com 新型免疫调节药物(例如β干扰素)治疗在II期临床试验中显示出很大前景。[55]Kuhl U, Pauschinger M, Schwimmbeck PL, et al. Interferon-beta treatment eliminates cardiotropic viruses and improves left ventricular function in patients with myocardial persistence of viral genomes and left ventricular dysfunction. Circulation. 2003 Jun 10;107(22):2793-8.http://circ.ahajournals.org/content/107/22/2793.fullhttp://www.ncbi.nlm.nih.gov/pubmed/12771005?tool=bestpractice.com
巨细胞心肌炎
这是一种罕见且急进性疾病,很可能是心肌炎的所有病因中死亡率最高的疾病。[7]Rosenstein ED, Zucker MJ, Kramer N. Giant cell myocarditis: most fatal of autoimmune diseases. Semin Arthritis Rheum. 2000 Aug;30(1):1-16.http://www.ncbi.nlm.nih.gov/pubmed/10966208?tool=bestpractice.com 虽然研究显示,积极的免疫抑制方案对存活率的提高不显著,但有限的数据表明,该治疗足以延长生命至能进行更有效的心脏移植治疗。[8]Shih JA, Shih JA. Small steps for idiopathic giant cell myocarditis. Curr Heart Fail Rep. 2015 Jun;12(3):263-8.http://www.ncbi.nlm.nih.gov/pubmed/25895034?tool=bestpractice.com[52]Cooper LT Jr, Berry GJ, Shabetai R; Multicenter Giant Cell Myocarditis Study Group Investigators. Idiopathic giant-cell myocarditis - natural history and treatment. N Engl J Med. 1997 Jun 26;336(26):1860-6.http://www.nejm.org/doi/full/10.1056/NEJM199706263362603#t=articlehttp://www.ncbi.nlm.nih.gov/pubmed/9197214?tool=bestpractice.com[56]Cooper LT Jr, Hare JM, Tazelaar HD, et al; Giant Cell Myocarditis Treatment Trial Investigators. Usefulness of immunosuppression for giant cell myocarditis. Am J Cardiol. 2008 Dec 1;102(11):1535-9.http://www.ncbi.nlm.nih.gov/pubmed/19026310?tool=bestpractice.com
自身免疫相关心肌炎
过敏性心肌炎
过敏性心肌炎被认为与各种药物的过敏反应相关。消除致病药物并进行全身性皮质类固醇治疗后,通常出现临床改善。[57]Kim CH, Vlietstra RE, Edwards WD, et al. Steroid-responsive eosinophilic myocarditis: Diagnosis by endomyocardial biopsy. Am J Cardiol. 1984 May 15;53(10):1472-3.http://www.ncbi.nlm.nih.gov/pubmed/6720598?tool=bestpractice.com
查格斯心肌炎
查格斯病是全球心肌炎的最常见病因。在感染的急性阶段进行抗寄生虫治疗通常能治愈。目前,有 2 种疗效已证实的药物可用于治疗急性期和早期慢性期查格斯病:苄硝唑和硝呋替莫。这些药物在美洲可获得,以用于治疗查格斯病;但在一些国家(例如美国),其供药受限。此病的心力衰竭治疗主要为对症治疗。由于心脏传导异常及室性心律失常,常常需要永久性起搏器及除颤器。免疫抑制疗法具有争议;难治性心力衰竭常常需要心脏移植。[11]Pinney SP, Mancini DM. Myocarditis and specific cardiomyopathies - endocrine disease and alcohol. In: Fuster V, Alexander RW, O'Rourke FA, eds. Hurst's the heart, 11th ed. New York, NY: McGraw-Hill; 2004:1949-1974.