静脉注射免疫球蛋白治疗成人特发性慢性心肌病和持续性细小病毒B19感染：一项前瞻性、双盲、随机、安慰剂对照临床试验。
Intravenous immunoglobulin therapy in adult patients with idiopathic chronic cardiomyopathy and cardiac parvovirus B19 persistence: a prospective, double-blind, randomized, placebo-controlled clinical trial.
作者信息
Hazebroek Mark R, Henkens Michiel T H M, Raafs Anne G, Verdonschot Job A J, Merken Jort J, Dennert Robert M, Eurlings Casper, Abdul Hamid Myrurgia A, Wolffs Petra F G, Winkens Bjorn, Brunner-La Rocca Hans-Peter, Knackstedt Christian, van Paassen Pieter, van Empel Vanessa P M, Heymans Stephane R B
机构信息
Department of Cardiology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Center, Maastricht, The Netherlands.
Department of Clinical Genetics, Maastricht University Medical Center, Maastricht, The Netherlands.
出版信息
Eur J Heart Fail. 2021 Feb;23(2):302-309. doi: 10.1002/ejhf.2082. Epub 2021 Jan 7.
AIMS
Previous uncontrolled studies suggested a possible benefit of intravenous immunoglobulin (IVIg) in parvovirus B19 (B19V)-related dilated cardiomyopathy (DCM). This randomized, double-blind, placebo-controlled, single-centre trial investigated the benefits of IVIg beyond conventional therapy in idiopathic chronic DCM patients with B19V persistence.
METHODS AND RESULTS
Fifty patients (39 men; mean age 54 ± 11 years) with idiopathic chronic (>6 months) DCM on optimal medical therapy, left ventricular ejection fraction (LVEF) <45%, and endomyocardial biopsy (EMB) B19V load of >200 copies/µg DNA were blindly randomized to either IVIg (n = 26, 2 g/kg over 4 days) or placebo (n = 24). The primary outcome was change in LVEF at 6 months after randomization. Secondary outcomes were change in functional capacity assessed by 6-min walk test (6MWT), quality of life [Minnesota Living with Heart Failure Questionnaire (MLHFQ)], left ventricular end-diastolic volume (LVEDV), and EMB B19V load at 6 months after randomization. LVEF significantly improved in both IVIg and placebo groups (absolute mean increase 5 ± 9%, P = 0.011 and 6 ± 10%, P = 0.008, respectively), without a significant difference between groups (P = 0.609). Additionally, change in 6MWT [median (interquartile range) IVIg 36 (13;82) vs. placebo 32 (5;80) m; P = 0.573], MLHFQ [IVIg 0 (-7;5) vs. placebo -2 (-6;6), P = 0.904] and LVEDV (IVIg -16 ± 49 mL/m vs. placebo -29 ± 40 mL/m ; P = 0.334) did not significantly differ between groups. Moreover, despite increased circulating B19V antibodies upon IVIg administration, reduction in cardiac B19V did not significantly differ between groups.
CONCLUSION
Intravenous immunoglobulin therapy does not significantly improve cardiac systolic function or functional capacity beyond standard medical therapy in patients with idiopathic chronic DCM and cardiac B19V persistence.
CLINICAL TRIAL REGISTRATION
ClinicalTrials.gov ID NCT00892112.
目的
既往非对照研究提示静脉注射免疫球蛋白（IVIg）可能对细小病毒B19（B19V）相关的扩张型心肌病（DCM）有益。本随机、双盲、安慰剂对照、单中心试验研究了在持续性B19V感染的特发性慢性DCM患者中，IVIg在常规治疗基础上的益处。
方法与结果
50例（39例男性；平均年龄54±11岁）接受最佳药物治疗的特发性慢性（>6个月）DCM患者，左心室射血分数（LVEF）<45%，且心内膜心肌活检（EMB）显示B19V负荷>200拷贝/μg DNA，被随机分为IVIg组（n = 26，4天内给予2 g/kg）或安慰剂组（n = 24）。主要结局是随机分组后6个月时LVEF的变化。次要结局包括通过6分钟步行试验（6MWT）评估的功能能力变化、生活质量[明尼苏达心力衰竭生活问卷（MLHFQ）]、左心室舒张末期容积（LVEDV）以及随机分组后6个月时EMB的B19V负荷。IVIg组和安慰剂组的LVEF均显著改善（绝对平均增加分别为5±9%，P = 0.011和6±10%，P = 0.008），但两组间无显著差异（P = 0.609）。此外，6MWT的变化[中位数（四分位间距）IVIg组为36（13；82）m，安慰剂组为32（5；80）m；P = 0.573]、MLHFQ[IVIg组为0（-7；5），安慰剂组为-2（-6；6），P = 0.904]和LVEDV（IVIg组为-16±49 mL/m，安慰剂组为-29±40 mL/m；P = 0.334）在两组间均无显著差异。此外，尽管IVIg给药后循环中B19V抗体增加，但两组间心脏B19V的减少无显著差异。
结论
对于特发性慢性DCM且心脏存在B19V持续感染的患者，静脉注射免疫球蛋白治疗在标准药物治疗基础上并不能显著改善心脏收缩功能或功能能力。
临床试验注册
ClinicalTrials.gov标识符NCT00892112。
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