转甲状腺素蛋白淀粉样变心肌病的临床特点

Clinical Features of Transthyretin Amyloidotic Cardiomyopathy

目的:转甲状腺素蛋白淀粉样变心肌病(ATTR-CM)是一种临床异质性高、以进行性心力衰竭为特征的心肌病,易误诊且预后不良。本研究旨在描述该病的临床特点,以提高临床医师对该病的认识。方法:回顾性分析2000年至2019年北京协和医院确诊的30例ATTR-CM住院患者资料,收集患者的临床信息,包括年龄、性别、首发症状、症状发作至确诊时间、主要表现、心电图和超声心动图表现以及预后情况。结果:30例患者的中位发病年龄为45(34,56)岁,其中男性23例(76.7%),29例为突变型,1例为野生型,从症状发作至确诊中位时间为30(21,40)个月。患者的首发临床表现以周围神经及自主神经系统受累为主(87.7%)。14例(46.7%)患者有心脏受累症状,主要表现为晕厥(43.3%)、气短(33.3%)和下肢肿(23.3%)。超声心动图提示,所有患者(100%)均有左心室肥厚,21例(70.0%)合并舒张功能异常,14例(46.7%)合并心包积液,6例(20.0%)左心室射血分数<50%。22例(73.3%)患者心电图结果异常,最常见的表现是假性梗死Q波(46.7%),其次为传导异常(43.3%)和肢体导联低电压(43.3%)。2例突变型ATTR-CM患者分别接受肝脏移植和间断氯苯唑酸治疗,其余患者仅接受对症治疗。5例患者失访,其余25例患者中位随访18(8,42)个月的结果显示,患者确诊ATTR-CM后的中位生存期为30(20,39)个月;13例(52.0%)患者死亡,死因以心力衰竭(7例,53.8%)及心原性猝死(4例,30.8%)为主。结论:ATTR-CM临床异质性高,多以周围神经和自主神经病变起病,心脏受累明确但症状不突出,超声心动图表现为左心室肥厚且左心室射血分数保留;心电图异常主要为假性梗死Q波、肢体导联低电压、传导异常;在无有效药物干预下总体预后不佳。

Objectives:Transthyretin amyloidotic cardiomyopathy(ATTR-CM)is a clinically heterogeneous cardiomyopathy characterized by progressive heart failure,which is easy to be misdiagnosed and related to poor prognosis.Clinical studies have proved that some drugs can improve the prognosis of ATTR-CM.The purpose of this study is to describe the clinical characteristics aiming to improve the clinical understanding and awareness on this disease by medical professionals.Methods:In this single-center retrospective analysis,we included 30 in-patients diagnosed with ATTR-CM in Peking Union Medical College Hospital from 2000 to 2019.We collected and analyzed patients’clinical information including age,gender,onset symptoms,period from symptom onset to diagnosis,ECG and echocardiography manifestations and prognosis.Results:The onset age was 45(34,56)years old,23 patients(76.7%)were male.29 were mutant ATTR,1 was wild-type ATTR.The time from onset to diagnosis was 30(21,40)months.The onset manifestations were mainly peripheral and autonomic neuropathy(87.7%).There were 14 patients(46.7%)with cardiac involvement.The main symptoms of cardiac involvement were as follows:syncope(43.3%),shortness of breath(33.3%),and lower limb swelling(23.3%).Left ventricular hypertrophy was detected in all patients by echocardiography,left ventricular ejection fraction(LVEF)was reduced in 6 patients(20.0%).There were 21 patients(70.0%)with diastolic dysfunction,14 patients(46.7%)with pericardial effusion.Abnormal ECGs were obtained in 22 patients(73.3%),the common ECG feature was pseudo-infarct Q waves(46.7%),followed by conduction abnormalities(43.3%)and low voltage in limb leads(43.3%).Two patients with mutant ATTR underwent liver transplantation or intermittent administration of Tafamidis,respectively.The remaining patients only received symptomatic treatment.Five patients lost to followup.The median follow-up time was 18 months(8,42)for the remaining 25 patients.Follow-up results showed that the median survival time after confirmed diagnosis of ATTR-CM was 30(20,39)months.A total of 13 patients(52.0%,13/25)died,the main cause of death was heart failure(53.8%,7/13)and sudden cardiac death(30.8%,4/13).Conclusions:Clinical heterogeneity in ATTR-CM patients is high,and ATTR-CM usually starts with peripheral and autonomic neuropathy.The incidence of cardiac involvement is high,but the cardiac involvement related symptoms are not prominent.Echocardiography usually shows left ventricular hypertrophy and preserved ejection fraction.The main manifestations of abnormal ECG are pseudo-infarction Q wave,low voltage in limb leads and conduction abnormalities.The prognosis of ATTRCM is poor in the absence of effective medication.