A preliminary study of autoantibodies against the M2-muscarinic receptor in peripartum cardiomyopathy patients
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摘要: 目的:评估M2受体自身抗体(anti-M2-R)与围产期心肌病(PPCM)患者预后的相关性。方法:本研究为前瞻性单中心观察性研究。连续入选1998—2018年84例就诊于北京朝阳医院的PPCM患者。ELISA法检测血清anti-M2-R水平,根据检测结果分为anti-M2-R阴性组和阳性组。所有的PPCM患者均给予标准抗心力衰竭(心衰)治疗,专人定期随访,定期监测实验室指标、心脏超声和6分钟步行试验。经过平均5年的随访,比较两组患者临床相关指标和全因死亡率、心血管死亡率、心衰再住院率的差异。结果:80例PPCM患者完成了最终数据分析,其中anti-M2-R阳性组37例,anti-M2-R阴性组43例。两组患者治疗后左心室舒张末期内径、左室射血分数、心功能分级、6分钟步行距离均有明显改善(P<0.01)。其中,anti-M2-R阴性组患者美托洛尔最大耐受剂量更高[(38.4±5.0) mg, 2次/d∶(26.6±4.3) mg, 2次/d,P<0.01],滴定速度更快[(67.0±10.9)d∶(82.8±11.9)d,P<0.01],左室射血分数更高[(62.4±6.7)%∶(57.5±7.4)%,P<0.05]。Anti-M2-R阴性组心衰再住院率显著降低(P<0.05),但两组间全因死亡率和心血管死亡率没有统计学差异。结论:PPCM患者的整体预后相对较好,尤其是anti-M2-R阴性的患者,这可能与自主神经系统的调节有关。anti-M2-R可能参与PPCM的发病,需进一步研究证实并阐明其潜在机制。Abstract: Objective: To evaluate the association of autoantibodies against the M2-muscarinic receptor(anti-M2-R) on prognosis of peripartum cardiomyopathy(PPCM) patients with standard treatment.Methods: This was a single center, prospective, observational study, which began in January 1998 and ended in December 2018. The 84 consecutive patients with newly diagnosed PPCM were enrolled at Beijing Chao-Yang Hospital. Synthetic peptides corresponding to the M2 receptor served as the target antigens in an ELISA experiment. They were used to screen sera of the 84 PPCM patients, who were separated into anti-M2-R-negative or positive group. All the PPCM patients received standard therapy regimens and they were assigned to one of the designated investigators and received follow-up examinations for 5 years after the initiation of the study. Clinical assessment, echocardiography examination and 6-minute walk test were performed regularly. The primary endpoint events were all-cause mortality, cardiovascular mortality, and re-hospitalization for heart failure.Results: The 80 PPCM patients completed the final data analysis, including 37 in the anti-M2-R(+) group and 43 in the anti-M2-R(-) group. Both groups showed improvement in the left ventricular end-diastolic dimensions, the left ventricular ejection fraction, New York Heart Association functional classes and 6-minutes walk distance with standard treatment regimens and follow-up for 5 years(all P<0.01). Anti-M2-R(-) patients had greater tolerance and more rapidly titrated to metoprolol(38.4±5.0 mg bid: 26.6±4.3 mg bid, P<0.01; 67.0±10.9 days: 82.8±11.9 days, P<0.01), and they had better improvement in left ventricular ejection fraction than patients in the anti-M2-R(+) group(62.4±6.7%: 57.5±7.4%, P<0.05). Anti-M2-R(-) patients had a marked decrease of re-hospitalization(P<0.05) but not of all-cause mortality or cardiovascular mortality.Conclusion: PPCM patients have a relatively better prognosis than other patients, especially anti-M2-R(-) patients, which may be related to the regulation of autonomic nervous system. We posit that anti-M2-R may be involved in the pathogenesis of PPCM, which need further study to confirm and clarify its potential mechanism.
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Key words:
- peripartum cardiomyopathy /
- heart failure /
- anti-M2-R /
- prognosis
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