Recent advances in the diagnostic methods and therapeutic strategies of transthyretin cardiac amyloidosis

Cardiac amyloidosis is a progressive disease characterized by the buildup of amyloid fibrils in the extracellular space of the heart.It is divided in 2 main types,immunoglobulin light chain amyloidosis and transthyretin amyloidosis(ATTR),and ATTR amyloidosis is further divided in 2 subtypes,non-hereditary wild type ATTR and hereditary mutant variant amyloidosis.Incidence and prevalence of ATTR cardiac amyloidosis is increasing over the last years due to the improvements in diagnostic methods.Survival rates are improving due to the development of novel therapeutic strategies.Tafamidis is the only disease-modifying approved therapy in ATTR amyloidosis so far.However,the most recent advances in medical therapies have added more options with the potential to become part of the therapeutic armamentarium of the disease.Agents including acoramidis,eplontersen,vutrisiran,patisiran and anti-monoclonal antibody NI006 are being investigated on cardiac function in large,multicenter controlled trials which are expected to be completed within the next 2-3 years,providing promising results in patients with ATTR cardiac amyloidosis.However,further and ongoing research is required in order to improve diagnostic methods that could provide an early diagnosis,as well as survival and quality of life of these patients.

Clinical features of retinal amyloid angiopathy with transthyretin Gly83Arg variant

AIM:To report on the clinical features of patients with retinal amyloid angiopathy(RAA)who were identified to be caused by the transthyretin(TTR)Gly83Arg variant.METHODS:Case series of five patients diagnosed with RAA was collected at Affiliated Hospital of Zunyi Medical University from January 2010 to December 2021.The clinical features,therapeutic strategies,and prognoses of all patients were reviewed.RESULTS:Five patients with a mean age of 52.00±7.23y were diagnosed as RAA.These patients were previously diagnosed with hereditary transthyretin amyloidosis caused by the TTR Gly83Arg variant.Vitreous opacity was found in all 10 eyes,and 7 eyes developed RAA 2 to 20y after the onset of hereditary transthyretin amyloidosis.The clinical manifestations were recurrent vitreous hemorrhage in 2 eyes(29%),neovascular glaucoma in 2 eyes(29%),and iris neovascularization in 1 eye(14%).Microangioma lesions were found in all affected eyes that underwent fundus fluorescein angiography(FFA)in this group of cases,and the incidence of the retinal non-perfusion area was 67%.Although no cases of retinal neovascularization were found,the prognosis of visual acuity was not ideal.CONCLUSION:This is the first report of RAA in patients with the TTR Gly83Arg variant.Complications such as RAA and glaucoma will seriously affect the visual prognosis of patients.Thereafter,regular ophthalmic follow-up of patients with hereditary transthyretin amyloidosis is essential.And FFA after vitrectomy is very important,which can help ophthalmologists detect RAA earlier and treat it in time.

Rare manifestation of familial vitreous amyloidosis caused by Gly103Arg transthyretin

AIM:To identify and analyze the genotype of the patients with special ocular manifestations of familial vitreous amyloidosis(FVA)in a Chinese Han family.METHODS:Pars plana vitrectomy(PPV)surgery was performed on a 52-year-old Chinese woman presented with vitreous amyloidosis and progressive visual impairment,without evidence of cardiac,renal,gastrointestinal,central nervous system or peripheral nervous system dysfunction.During the surgery,the patient presented with a gray-white dense and thick cotton woollike change in the vitreous body,accompanied by complete retinal detachment.Additionally,hard,free and movable yellow-white deposits were observed in the posterior pole and surrounding retina,the vitreous and subretinal deposits were examined by Congo red staining and immunohistochemical pathological examination,and whole exome sequencing was performed on blood samples from the patient and her cousin.RESULTS:During the operation,it was discovered that there was a complete detachment of the retina and a significant amount of hard,free-floating yellow-white deposits were observed beneath the posterior pole and surrounding retina.This is an exceedingly rare ocular manifestation.Pathological examination of the vitreous and subretinal deposit specimens revealed positive Congo red staining,as well as elevated vascular endothelial growth factor(VEGF)expression in vascular endothelial cells within the sediment specimens upon immunohistochemical examination.The patient and her cousin both exhibited a heterozygous mutation in Glyl03Arg within the transthyretin(TTR)gene,resulting in a substitution of glycine(Gly)at position 103 with arginine(Arg).CONCLUSION:FVA may present with various ocular manifestations,but panretinal detachment is a rare occurrence.In cases where retinal detachment persists for an extended period of time,amyloid deposits may form under the retina through retinal tears,leading to subretinal deposits that can impede retinal reattachment and negatively impact visual prognosis.Elevated levels of VEGF in the eyes of FVA patients may indicate an overexpression state,necessitating careful postoperative follow-up.The heterozygous mutation Gly103Arg may represent a unique pathogenic site in Chinese individuals.

Screening for Transthyretin Cardiac Amyloidosis in Patients with Bilateral Carpal Tunnel Syndrome: Identifying Missed Opportunities for Early Detection and Treatment

Purpose: Transthyretin cardiac amyloidosis (ATTR-CA) has been linked to many extra-cardiac manifestations including bilateral carpal tunnel syndrome (CTS). The aim of this study is to analyze patients with bilateral CTS to identify patients with high-risk features or “red flags” for ATTR-CA, identify if systematic screening was done for ATTR-CA and define opportunities for improved detection. Methods: Out of >5000 patients with bilateral CTS evaluated in a single tertiary care center in Southeast Michigan (2010-2016), we retrospectively studied a focused population of patients: men > 50 years and women > 60 years old with bilateral CTS and atrial fibrillation (n = 295). Baseline demographic, comorbidities, and electrocardiographic and echocardiographic findings were analyzed. A high-risk group suspicious for ATTR-CA was identified as patients with bilateral CTS, atrial fibrillation, and concomitant “red flags” including heart failure and left ventricular hypertrophy. Results: Out of 295 patients, 51.2% were female, 75.6% were White, and 22.4% were African American. Upon comparing the high-risk group (n = 67) with the remaining study population (n = 228), both diagnosis of ATTR-CA and mortality were higher among the high-risk group (7.5% vs 0.4% and 43.3% vs 24.6%, respectively, P = 0.003). Conclusions: A substantial number of bilateral CTS patients had additional “red flags” warranting formal evaluation for ATTR-CA;however, systematic evaluation for cardiac amyloidosis was not performed in many patients. This emphasizes that Multidisciplinary collaboration is needed to create a systematic workflow and to raise awareness amongst cardiologists and other physicians for suspecting ATTR-CA in bilateral CTS patients who have additional “red flags”.

Repression of retinal microvascular endothelial cells by transthyretin under simulated diabetic retinopathy conditions

AIM： To investigate biological effects of transthyretin （TTR） on the development of neovascularization under simulated diabetic retinopathy （DR） condition associated with high glucose and hypoxia. METHODS： Human retinal microvascular endothelial cells （hRECs） were cultured in normal and simulated DR environments with high glucose and hypoxia. The normal serum glucose concentration is approximately 5.5 mmol/L; thus, hyperglycemia was simulated with 25 mmol/L glucose, while hypoxia was induced using 200 μmol/L CoCI. The influence of TTR on hRECs and human retinal pigment epithelial cells （hRPECs） was determined by incubating the cells with 4μmol/L TTR in normal and abnormal media. A co -culture system was then employed to evaluate the effects of hRPECs on hRECs. RESULTS： Decreased hRECs and hRPECs were observed under abnormal conditions, including high- glucose and hypoxic media. In addition, hRECs were significantly inhibited by 4 pmol/L exogenous TTR during hyperglycemic culture. During co-culture, hRPECs inhibited hRECs in both the normal and abnormal environments. CONCLUSION： hREC growth is inhibited by exogenous TTR under simulated DR environments with highglucose and hypoxic, particularly in the medium containing 25 mmol/L glucose, hRPECs, which manufacture TTR in the eye, also represses hRECs in the same environment. TTR is predicted to inhibit the proliferation of hRECs and neovascularization.

Negative effects of transthyretin in high myopic vitreous on diabetic retinopathy

AIM：To analyze the relationship between vitreous transthyretin（TTR） levels,high myopia and diabetic retinopathy（DR）.METHODS：We selected 6722 individuals from the southern Jiangsu Province for diabetes and ophthalmic examinations.The TTR concentration in the vitreous of 50 patients with high myopia and diabetes,50 patients with only DR,and 20 healthy controls were determined by ELISA.Key factors in Tie2 pathway in DR development including vascular endothecial growth factor（VEGF）,Tie2,Angpt1,Angpt2,vascular endothelial growth factor receptor（VEGFR） 1 and VEGFR2 were also detected by ELISA.RESULTS：The prevalence of DR in patients with diabetes and myopia [〈6.00 diopter（D）],diabetes and high myopia（〉6.00 D）,and diabetes without myopia were 11.1%,2.5%,and 60.0%,respectively.The vitreous TTR concentration of patients with diabetes and high myopia was approximately 6.5-and 4.2-times higher than those of patients with DR and healthy controls,respectively（P〈0.05）.Following the vitreous TTR concentration,the levels of VEGF,Tie2,Angpt1,Angpt2,VEGFR1 and VEGFR2 in vitreous of diabetes and high myopia patients,DR patients and healthy controls were detected as dramatically fluctuated.CONCLUSION：The results suggest that TTR can affect the vitreous contents of key factors in Tie2 pathway for neovascularization,and there should be a protective association between abundant TTR levels in the vitreous of highly myopic patients and a decreased risk of DR.

Transthyretin Arg-83 mutation in vitreous amyloidosis

Both of the patients in the report had floaters and progressive vision loss for years. Two cases of familial vitreous amyloidosis occurred in three generations with typical white fibrilar opacities in the vitreous body. Pars plana vitrectomy was performed in the two patients. The vitreous specimens were subjected to histopathological examination. The specimens showed typical microscopic features of amyloidosis with Congo red stain and non-branching fibrils were seen randomly distributed with 5-10nm in diameter on a transmission electron microscope. All of the exons of the transthyretin gene were amplified with DNA isolated from the peripheral blood cells. Bi-directional sequencing of the transthyretin gene revealed a single base-pair substitution, which results in an amino acid substitution at position83, glycine to arginine (transthyretin Arg-83).

Symptomatic Val122del mutated hereditary transthyretin amyloidosis: Need for early diagnosis and prioritization for heart and liver transplantation

Background: Hereditary transthyretin(ATTRv) amyloidosis is an autosomal dominant disease linked to transthyretin gene mutations which cause instability of the transthyretin tetramer. After dissociation and misfolding they reassemble as insoluble fibrils(i.e. amyloid). Apart from the common Val30 Met mutation there is a very heterogeneous group of non-Val30 Met mutations. In some cases, the clinical picture is dominated by a rapidly evolving restrictive and hypertrophic cardiomyopathy. Methods: A case series of four liver recipients with the highly clinically relevant, rare and particularly aggressive Val122 del mutation is presented. Medical and surgical therapeutic options, waiting list policy for ATTRv-amyloidosis, including the need for heart transplantation, and status of heart-liver transplantation are discussed. Results: Three patients needed a staged(1 patient) or simultaneous(2 patients) heart-liver transplant due to rapidly progressing cardiac failure and/or neurologic disability. Domino liver transplantation was impossible in two due to fibrotic hepatic transformation caused by cardiomyopathy. After a follow-up ranging from 3.5 to 9.5 years, cardiac(allograft) function was maintained in all patients, but neuropathy progressed in three patients, one of whom died after 80 months. Conclusions: This is the first report in(liver) transplant literature about the rare Val122 del ATTRv mutation. Due to its aggressiveness, symptomatic patients should be prioritized on the liver and, in cases with cardiomyopathy, heart waiting lists in order to avoid the irreversible neurological and cardiac damage that leads to a rapid lethal outcome.

Wild type transthyretin amyloidosis,a reason not to be forgotten for heart failure of preserved ejection fraction in the elderly

Amyloidosis is a multisystem disease that is characterized by deposition of fibrils in extracellular tissue,which mainly involves the kidney,heart,and autonomic nervous system.Two types of amyloidosis typically infiltrate the heart,including immunoglobulin light-chain(AL)and amyloid transthyretin(ATTR).ATTR is further subdivided into wild-type ATTR and variant ATTR caused by point mutations in the TTR gene.[1]Wild-type ATTR is considered as not uncommon in older patients with heart failure.Recently,a comprehensive set of consensus recommendations for the suspicion and diagnosis of ATTR was published,with particular focus on the combined application of noninvasive methods.[2]We present here a case of wild-type TTR cardiac amyloidosis(ATTRwt-CA),which was diagnosed by noninvasive modalities,and provide an overview of the recommended diagnostic approach of CA.Furthermore,to the best of our knowledge,this is the first Chinese case of ATTRwt-CA reported to date.

Transthyretin—A Key Gene Involved in Regulating Learning and Memory in Brain, and Providing Neuroprotection in Alzheimer Disease via Neuronal Synthesis of Transthyretin Protein

Transthyretin (TTR), a carrier protein present in the liver and choroid plexus of the brain, has been shown to be responsible for binding thyroid hormone thyroxin (T4) and retinol in plasma and cerebrospinal fluid (CSF). TTR aids in sequestering of beta-amyloid peptides Aβ deposition, and protects the brain from trauma, ischemic stroke and Alzheimer disease (AD). Accordingly, hippocampal gene expression of TTR plays a significant role in learning and memory as well as in simulation of spatial memory tasks. TTR via interacting with transcription factor CREB regulates this process and decreased expression leads to memory deficits. By different signaling pathways, like MAPK, AKT, and ERK via Src, TTR provides tropical support through megalin receptor by promoting neurite outgrowth and protecting the neurons from traumatic brain injury. TTR is also responsible for the transient rise in intracellular Ca2+ via NMDA receptor, playing a dominant role under excitotoxic conditions. In this review, we tried to shed light on how TTR is involved in maintaining normal cognitive processes, its role in learning and memory, under memory deficit conditions;by which mechanisms it promotes neurite outgrowth;and how it protects the brain from Alzheimer disease (AD).

Multi-modality imaging in transthyretin amyloid cardiomyopathy

Transthyretin amyloid(TTR)cardiomyopathy is a disease of insidious onset,which is often accompanied by debilitating neurological and/or cardiac complications.The true prevalence is not fully known due to its elusive presentation,being often under-recognized and usually diagnosed only late in its natural history and in older patients.Because of this,effective treatment options are usually precluded by multiple comorbidities and frailty associated with such patients.Therefore,high clinical suspicion with earlier and better detection of this disease is needed.In this review,the novel applications of multimodality imaging in the diagnostic pathway of TTR cardiomyopathy are explored.These include the complimentary roles of transthoracic echocardiography,cardiac magnetic resonance,nuclear scintigraphy and positron emission tomography in quantifying cardiac dysfunction,diagnosis and risk stratification.Recent advances in novel therapeutic options for TTR have further enhanced the importance of a timely and accurate diagnosis of this disease.

Early and aggressive presentation of wild-type transthyretin amyloid cardiomyopathy:A case report

BACKGROUND Wild-type transthyretin amyloidosis(ATTRwt)is the most common form of transthyretin amyloid cardiomyopathy,occurring mostly over age of 60 years(mean age of 80 years).Mean survival without treatment is 3.6 years,making early detection imperative.We report an unusual case of a 58-year-old patient with ATTRwt cardiomyopathy requiring heart transplantation.CASE SUMMARY A 58-year-old male presented with progressive fatigue,shortness of breath,weight gain,leg swelling,orthopnoea,and paroxysmal nocturnal dyspnoea for several months.Approximately ten months before this clinical presentation,the patient had first received a diagnosis of heart failure with reduced ejection fraction(EF)of 15% to 20%.The patient was started on appropriate guidelinedirected medical therapy with only mild improvement in his EF.Upon further investigation,echocardiogram,technetium pyrophosphate scan(Tc PYP),and cardiac magnetic resonance imaging(cMRI)suggested a diagnosis of amyloidosis,and ATTRwt was subsequently confirmed with native heart tissue biopsy,congo red staining,liquid chromatography-tandem mass spectrometry,and genetic testing.The patient was successfully treated with heart transplantation and is doing well post-transplant.CONCLUSION Wild-type ATTR amyloidosis should be kept on differentials in all patients(even less than 60 years old)with non-ischemic cardiomyopathy,especially in the setting of increased ventricular wall thickness and other classic echocardiogram,cMRI,and Tc PYP findings.Early diagnosis and management can be consequential in improving patient outcomes.

Vitreous amyloidosis caused by a Lys55Asn variant in transthyretin: A case report

BACKGROUND Amyloidosis is caused by misfolding of proteins and is characterized by formation of extracellular aggregates of insoluble fibrin.The primary effects in the eye include sharp deterioration of visual acuity as a result of vitreous opacity.According to the local and systemic distribution characteristics of amyloid deposits and their fibrin components,amyloidosis can be classified as primary,secondary or familial.Therefore,we report a typical case of vitreous amyloidosis in hereditary transthyretin amyloidosis(hATTR)to improve ophthalmologists’understanding of the disease and reduce misdiagnosis and recurrence.CASE SUMMARY The patient was a 49-year-old man who complained of progressive visual decline in both eyes over a 2-mo period.No systemic diseases such as diabetes or hypertension were reported,and no obvious family history of disease was identified.The patient’s visual acuity was HM/10 cm in the right eye and 0.06 in the left eye.He had a transparent cornea in both eyes,with a normal anterior depth,clear aqueous humor,no obvious iris abnormalities,round pupils of approximately 3 mm in diameter,normal direct and indirect light reflexes,and normal intraocular pressure.After various examinations,the patient was diagnosed with binocular vitreous amyloidosis secondary to hATTR associated with a Lys55Asn variant in TTR.The binocular visual acuity recovered to 1.0 after binocular vitrectomy.CONCLUSION Vitreous amyloidosis is rare in the clinic and gene testing can assist the diagnosis accurately and effectively.

Elevated interleukin-6 levels are associated with impaired outcome in cardiac transthyretin amyloidosis

BACKGROUND Elevated interleukin(IL)-6-levels have been described in familial variant transthyretin amyloidosis(ATTRv)associated polyneuropathy and heart failure.However,IL-6 in cardiac ATTR amyloidosis(ATTR-CM)and its prognostic value have not been investigated yet.AIM We aim to study the correlation between IL-6 levels with clinical presentation(Gillmore-class)and outcome[heart transplantation or death(htx/death)],or the combined endpoint of cardiac decompensation or htx/death in ATTR-CM.METHODS IL-6 levels of 106 ATTR-CM patients[54 wild-type ATTRwt,52 ATTRv-CM],15 asymptomatic carriers of ATTR mutations(aATTRv-CM)and 27 healthy donors were quantified using Luminex technology.Statistical analysis was performed using parametric survival regression models.RESULTS We found that IL-6 levels from wild-type ATTR patients were significantly elevated compared to healthy controls,while aATTRv-CM carriers and ATTRv-CM patients did not show a significant difference.IL-6 levels showed significantly higher values in increasing Gillmore classes.Univariate analyses revealed association of low IL-6 levels with cardiac decompensation and htx/death[odds ratio:0.26(0.09-0.72),P=0.01]and htx/death[odds ratio:0.15(0.04-0.58),P=0.006].However,in the multivariate model,no significant improvement of risk prediction was seen for IL-6,while established prognostic factors were significantly associated with outcome.CONCLUSION Raised IL-6 levels correlate with clinical presentation and are associated with worse outcome in ATTR-CM but do not improve stratification in addition to established risk factors.

Carpal Tunnel Syndrome: A Marker for Amyloidosis

Introduction: Amyloidosis are systemic conditions and carpal tunnel syndrome (CTS) precedes the principal systemic complications and can be used as an early marker. Our objective was to determine the frequency of amyloid deposition in idiopathic CTS and its systemic impact. Methods: We retrospectively evaluated patients with CTS between September 2019 to January 2020. Samples from the anterior carpal ligament were pathologically evaluated and amyloid deposition was confirmed by apple-green birefringence on polarized light using Congo red stain. When amyloid was detected we performed genetic testing for transthyretin variants (ATTRv), immunofixation electrophoresis in serum and urine for light chains and multidisciplinary evaluation. Results: Thirty consecutive patients were included, 19 women, 11 men, mean age 70 years old (range 42 - 89 years). We identified 3 patients (10%) with amyloid deposits (mean age: 78.6 years, 2 men, 1 woman). Genetic testing for ATTRv and light chains studies were negative. During follow-up: The first patient required aortic valve replacement. The second patient developed progressive cardiac failure with syncopal episodes, atrioventricular block and atrial fibrillation and required a pacemaker and anticoagulation. The third patient had unexplained chronic edemas. The cardiac evaluation in all 3 patients revealed left ventricular hypertrophy and myocardial uptake (Perugini Score > 2) in their nuclear bone scintigraphies with technetium pyrophosphate. Two patients were treated with tafamidis and one patient died due to refractory cardiac insufficiency. Discussion: Our findings underline the importance of investigating amyloidosis in idiopathic CTS. The identification of deposits allows early diagnosis of cardiac amyloidosis leading to timely intervention and treatment.

轻链型和转甲状腺素蛋白心肌淀粉样变性临床特征的比较

目的:比较轻链型心肌淀粉样变性(AL-CA)和转甲状腺素蛋白心肌淀粉样变性(ATTR-CA)的临床特征。方法:回顾性收集2011年1月至2023年10月在北京大学第三医院住院确诊的AL-CA患者35例(AL-CA组)和ATTR-CA患者21例(ATTR-CA组)。比较两组临床表现、心电图、超声心动图和心脏磁共振成像(CMR)结果的差异。结果:与ATTR-CA组相比,AL-CA组男性比例较低(90.5%vs.54.3%,P=0.005),合并高血压的患者比例较高(9.5%vs.42.9%,P=0.009)。临床表现方面,AL-CA组水肿、蛋白尿、肾功能不全和浆膜腔积液较多见,血红蛋白和血浆白蛋白水平较低,而ATTR-CA组肢体麻木的发生率较高(P均<0.05)。心电图方面,AL-CA组的肢体导联低电压的发生率(57.1%vs.28.6%,P=0.038)高于ATTR-CA组,传导阻滞的发生率(14.3%vs.61.9%,P=0.001)低于ATTR-CA组。AL-CA组从首发症状到确诊时间较ATTR-CA组短[6.0(2.0,15.0)个月vs.35.0(14.0,56.5)个月,P=0.002]。AL-CA组与ATTR-CA组的超声心动图指标室间隔厚度分别为(13.3±2.0)mm vs(.15.7±2.2)mm(P=0.001);左心室质量分别为(198.4±67.8)g vs.(246.6±53.5)g(P=0.009);CMR指标室间隔厚度分别为(16.0±2.1)mm vs.(18.9±3.8)mm(P=0.033);左心室质量分别为(132.9±45.3)g vs.(194.7±50.8)g(P=0.011),AL-CA组左心室壁增厚程度较ATTR-CA组轻,但AL-CA组NYHA心功能分级Ⅲ~Ⅳ级患者的比例较高(48.6%vs.19.0%,P=0.027),N末端B型利钠肽原和心肌肌钙蛋白T水平较高(P均<0.05),1年生存率较低(65.7%vs.100%,P=0.001)。结论:AL-CA和ATTR-CA的临床特征和心电图表现不同。AL-CA左心室壁增厚程度虽然不及ATTR-CA显著,但心功能及预后更差。

转甲状腺素蛋白心脏淀粉样变的诊断与治疗研究进展

转甲状腺素蛋白心脏淀粉样变是由于转甲状腺素蛋白沉积于心脏所引起的心脏功能障碍,既往被认为是一种罕见病,其发病隐匿、进展迅速、致死率高。近年来,随着诊断技术的进步,该病的检出率不断提高,各种小分子药物的不断问世也改变了以往无药可医的局面,使其死亡率有所下降。本文主要归纳了近年来转甲状腺素蛋白心脏淀粉样变在诊断和治疗方面的最新进展。

超声心动图在鉴别诊断心肌淀粉样变性两种主要分型中的意义

目的研究超声心动图在鉴别诊断心肌淀粉样变性(cardiac amyloidosis,CA)两种主要分型——转甲状腺素蛋白型(ATTR)和免疫球蛋白轻链型(AL)中的价值。方法回顾性分析2021年11月至2024年1月西安交通大学第一附属医院确诊的50例CA患者超声心动图参数,其中ATTR型6例,AL型44例,用t检验和χ2检验筛选出可能鉴别两种分型的参数,用受试者操作特征曲线(receiver operating characteristic curve,ROC曲线)分析这些参数对两种分型的鉴别诊断能力。结果ATTR组和AL组患者的一般情况、整体平均纵向应变值(global longitudinal strain,GLS)、心尖段平均应变与基底段平均应变的比值、射血分数与GLS比值(EFSR)、左室心肌最厚处厚度、左室壁相对厚度、房室瓣是否增厚、双房是否增大差异均无统计学意义(P>0.05)。ATTR组房间隔厚度大于AL组(P<0.05),ATTR组E/e’(频谱多普勒舒张早期峰值流速/组织多普勒频舒张早期峰值流速)比值大于AL组(P<0.05)。ROC曲线分析显示,房间隔厚度、E/e’鉴别两种分型的曲线下面积分别为0.891(95%CI:0.792~0.991),0.826(95%CI:0.698~0.955),两者联合诊断的灵敏度100.00%,特异度95.24%。结论超声心动图参数E/e’比值、房间隔厚度可能对鉴别诊断CA患者两种主要分型具有一定的临床意义。

氯苯唑酸治疗转甲状腺素蛋白淀粉样变性的临床研究进展

氯苯唑酸为转甲状腺素蛋白(TTR)的选择性稳定剂,用于治疗TTR淀粉样变性心肌病(ATTR-CM)和TTR淀粉样变性多发性神经病(ATTR-PN)。本文对氯苯唑酸的基本信息、有效性及安全性临床研究等进行综述,发现氯苯唑酸可通过抑制TTR四聚体的解离,减缓或阻止TTR淀粉样变性的进展。多项临床研究表明,氯苯唑酸具有良好的疗效和安全性,可以显著降低淀粉样变性患者全因死亡率和心血管相关住院率,延缓患者疾病进展。尽管氯苯唑酸治疗可能存在一定的局限性,但其仍然是用于治疗TTR淀粉样变性疾病的关键药物,也是第1种被批准用于治疗ATTR-CM的药物。

转甲状腺素蛋白淀粉样变心肌病一家系遗传学分析

目的:探讨转甲状腺素蛋白淀粉样变心肌病(ATTR-CM)的遗传学特征。方法:对1例以心肌肥厚所致心力衰竭为主要临床特征的ATTR-CM先证者的临床表型进行分析,通过高通量测序分析转甲状腺素蛋白(TTR)基因突变情况并进行Sanger测序验证。结果:先证者发病年龄较早,临床症状复杂。先证者及其妹妹、侄子、女儿4人存在TTR基因c.A163G(p.Lys55Glu)杂合突变。结论:本研究发现了TTR基因c.A163G(p.Lys55Glu)突变导致的ATTR-CM,异常TTR沉积主要累及心脏,症状复杂且不典型。