自身免疫性疾病合并系统性轻链淀粉样变性

育龄期女性,临床表现多系统损害、自身抗体阳性、补体下降,同时血免疫固定电泳见游离λ轻链单克隆条带;肾脏损害表现尿检异常伴血清肌酐升高,肾活检证实为肾脏淀粉样变性(AL型);皮肤脂肪组织、骨髓活检均示淀粉样变性。最终诊断自身免疫性疾病合并原发性系统性淀粉样变性(累及肾脏、皮肤、心脏、骨髓)。     

心脏淀粉样变性诊断与治疗(附病例介绍与分析)

心脏淀粉样变性（cardiac amyloidosis）指淀粉样物质在心脏内沉积，临床上常表现为限制性心肌病或难治性心力衰竭伴有或不伴有各种类型传导阻滞。心脏淀粉样变性见于多种系统性淀粉样变性。     

原发性轻链型淀粉样变性治疗中出现急性肝衰竭1例报告

正淀粉样变性常可累及肾脏、心脏、皮肤、消化系统和骨髓[1],分为原发性淀粉样变性、继发性淀粉样变性、透析相关性淀粉样变性及遗传性淀粉样变性。淀粉样变性的整体发病率低,其中原发性淀粉样变性发病率约为0.051‰~0.128‰[2]。该病的诊断主要依赖于病理学检查,早期临床症状隐匿,患者常因多脏器受损后就诊,临床上易误诊、漏诊。淀粉样变性累及肝脏时黄疸发生率较低(5%),且多为轻度黄     

轻链型心脏淀粉样变性预后评估方法

心脏淀粉样变性是系统性淀粉样变性累及心脏所致,较其他器官淀粉样变性的预后更差,特别是轻链型心脏淀粉样变性是该疾病的最严重形式。近些年来随着心脏成像技术的发展,如超声心动图,尤其是心脏磁共振技术的进展使人们对轻链型心脏淀粉样变性有了更多的认识,同时对于已明确诊断该疾病的患者,运用一些成像技术参数或生物标志物对轻链型心脏淀粉样变性的预后进行评估,可以更好地实施治疗,从而不断提高患者的预后水平。现从氨基末端前体B型利尿钠肽、每搏量指数、心肌细胞外体积、三尖瓣瓣环平面收缩期偏移、心肌应变、心脏磁共振的T2像、心脏磁共振的钆延迟强化等七个方面概述它们对轻链型心脏淀粉样变性的预后评估价值。     

磁共振影像技术在心脏淀粉样变性中的应用

系统性淀粉样变性是一组异质性疾病,其共同的特征是不同来源的错误折叠蛋白质沉积在全身多个组织器官.心脏是常见受累器官之一,心脏淀粉样变性的严重程度是影响患者预后的决定性因素.磁共振技术因具有出色的空间分辨率和高组织对比度,在心脏淀粉样变性的形态学评估、诊断、危险分层和预后评估等方面具有极为广阔的应用前景.本文就磁共振相关...     

伴心肌肌钙蛋白I持续升高和心绞痛症状的心肌淀粉样变性

<正>心肌肌钙蛋白(cTnI)被认为是心肌损伤的特异性标志物~([1])。临床上,cTnI升高常见于急性心肌梗死,也可见于心肌炎、充血性心力衰竭、心律失常、肺栓塞、慢性肾功能不全/血透患者及重症感染等患者~([2])。淀粉样变性属于系统性疾病,相对少见,累及心脏时,可出现多种临床表现,极易造成误诊和漏诊。本文报道1例心肌淀粉样变性,伴持续性cTnI升高和反复发作心绞痛的病例。病例资料患者女,66岁。因发现cTnI持续升高1年余入院。患者1年前无明     

腹壁脂肪活检联合激光显微切割/质谱分析辅助诊断多发性骨髓瘤合并重轻链淀粉样变性1例报告

笔者在国内首次通过腹壁脂肪活检联合激光显微切割/质谱分析(LMD/MS)辅助诊断1例多发性骨髓瘤合并重轻链淀粉样变性患者，强调LMD/MS在淀粉样变性分型中的重要性。当心脏磁共振的钆延迟强化阴性，通过肌钙蛋白T、纵向弛豫时间定量成像与心肌细胞外容积可辅助诊断心肌淀粉样变性。     

30例淀粉样变性患者的临床特点分析

目的 总结淀粉样变性的临床特征,提高对该病的认识水平。 方法 回顾北京友谊医院23年来30例诊断为淀粉样变性患者的临床资料、实验室检查结果以及治疗情况。 结果 系统性淀粉样变性12例,其中原发性9例、继发性1例、家族性2例;局限性淀粉样变性18例。男性17例,女性13例。系统性淀粉样变性患者中肾脏(75.00％)、肝脏(58.33％)、神经系统(58.33％)和心脏(50.00％)是常见的受累部位。常见临床表现为不明原因的乏力、体重减轻、水肿、大量蛋白尿、肝脏肿大、四肢麻木。局限性淀粉样变性主要累及皮肤、咽喉和消化道,多采取动态观察和局部手术切除治疗。 结论 淀粉样变性可累及多器官系统,临床表现多种多样,误诊率高,确诊需靠病理检查、刚果红染色。临床医师提高对本病警惕性是避免误诊的主要途径。     

肝淀粉样变性临床及影像分析

目的 探讨分析肝淀粉样变性的临床及影像学特点,为临床提供经验和参考。方法 回顾性分析解放军总医院第五医学中心2017年2月—2023年6月期间收治的12例经病理活检证实的肝淀粉样变性患者的各项资料,归纳分析患者的一般资料、临床表现、实验室检验和影像学表现等。结果 12例肝淀粉样变性患者的临床表现主要为腹胀、纳差、发现肝功能异常,入组患者中碱性磷酸酶升高者10例,谷氨酰转肽酶升高者11例,白蛋白降低者7例,肿瘤标志物全呈阴性者5例,CA125升高者4例,CA199升高者6例。12例均有肝脏体积增大,7例脾脏增大,7例有腹腔积液,9例增强扫描门静脉期及延迟期肝实质内可见“窗凌花”样斑片状低密度或低信号强化影。结论 肝淀粉样变性多见于中老年女性,主要临床表现为腹胀、纳差和肝功能异常,大部分患者可有碱性磷酸酶和谷氨酰转肽酶升高,部分肿瘤标志物异常,影像学多表现为肝脾增大,腹水和肝实质强化不均匀,可有类似“窗凌花”样强化,确诊肝淀粉样变性的主要手段是影像学表现结合肝穿刺活检病理结果。     

肾淀粉样变性病理诊断的体会

淀粉样变性可以分为系统性和局灶性两类.系统性淀粉样变性包括免疫球蛋白轻链（AL）、血清淀粉样A物质（AA）、家族性、衰老的系统性淀粉样变性和透析相关的淀粉样变性.局灶性淀粉样变则包括：局灶的AL淀粉样变以及与帕金森病和快速进展性疾病相关的阿尔茨海默病,克雅病;此外2型糖尿病也属此类.最常见的累及肾脏的淀粉样物质是AL、AA以及家族性淀粉样变性.笔者从肾活检病理角度谈谈对肾淀粉样变性诊断的体会.     

Syncope in cardiac amyloidosis and chronic ischemic heart disease: A case report

Primary systemic amyloidosis is a relatively uncommon disease characterized by the production and deposition of pathological insoluble fibrillar proteins in organs and tissues. It has been estimated that between one-third and one-half of all patients with primary amyloidosis experience clinically significant cardiac involvement. The present study reports a case involving a 77-year-old woman with ischemic heart disease who presented to the cardiology department because of syncope due to slow atrial fibrillation. Laboratory tests revealed a monoclonal spike in the gamma fraction and impairment of renal function, normocytic anemia, mild hypercalcemia, hypoalbuminemia and increased levels of beta-2 microglobulin. Suspicion of cardiac involvement was supported by the echocardiographic pattern and increased levels of troponin I and brain natriuretic peptide, along with clinical signs of heart failure and systemic amyloidosis diagnosis, confirmed by abdominal fat aspiration.     

Persistent Troponin Elevation in a Patient with Cardiac Amyloidosis

A 79‐year‐old patient repeatedly presented with chest discomfort and dyspnea on exertion. With echocardiography a prominent left ventricular and septal hypertrophy was detected with reduced left ventricular function. Despite successful revascularization and excellent results after stenting, the patient showed persistently elevated troponin levels. To investigate the abnormal findings of persistent troponin elevation, septal hypertrophy, and heart failure we performed endomyocardial biopsies which showed widespread myocardial amyloidosis. Amyloid subtyping revealed transthyretin amyloidosis. This is the first case showing persistent troponin elevation in a patient with tranthyretin amyloidosis. Very few other cases have been published on the topic of cardiac amyloidosis and troponin elevation so far. Our case serves as an illustrating example in the differential diagnosis of nonischemic causes of persistent troponin elevation. It is important to consider cardiac amyloidosis in patients with troponin elevation and heart failure since the clinical management differs significantly from other causes of heart failure. Copyright © 2009 Wiley Periodicals, Inc.     

Cardiac amyloidosis presenting with elevations of cardiac troponin I and angina pectoris.

We present the case of a 43-year-old male who was initially evaluated for angina pectoris and dyspnea. His CK, CK-MB, and cTnI were all elevated following a blood transfusion and he underwent coronary arteriography, which demonstrated no luminal obstructions. After several months, he was transferred to Mayo Clinic where diagnoses of fulminant cardiac amyloidosis and systemic multiple myeloma were established. The cTnI remained elevated despite normalization of the CK and CK-MB. Despite aggressive treatment, the patient died. Postmortem analysis demonstrated amyloid cardiac deposition including involvement of the coronary microvasculature. Electron microscopy revealed myocyte compression injury from amyloid infiltration. We believe this is the first report of elevated troponin I in a patient with cardiac amyloidosis. The electron microscopy in our case confirms cardiac damage as the mechanism for cTnI elevation. This observation strengthens our knowledge about the specificity of cTnI for the detection of cardiac injury.     

Evaluation and management of the cardiac amyloidosis

Cardiac amyloidosis describes clinically significant involvement of the heart by amyloid deposition, which may or may not be associated with involvement of other organs. The purpose of this review is to summarize the current state of evidence for the effective evaluation and management of cardiac amyloidosis. Acquired systemic amyloidosis occurs in more than 10 per million person-years in the U.S. population. Although no single noninvasive test or abnormality is pathognomonic of cardiac amyloid, case-control studies indicate that echocardiographic evidence of left ventricular wall thickening, biatrial enlargement, and increased echogenicity in conjunction with reduced electrocardiographic voltages is strongly suggestive of cardiac amyloidosis. Furthermore, newer echocardiographic techniques such as strain and strain rate imaging can demonstrate impairment in longitudinal function before ejection fraction becomes abnormal. Recent observational studies also suggest that cardiovascular magnetic resonance imaging yields characteristic findings in amyloidosis, offering promise for the early detection of cardiac involvement, and the presence of detectable cardiac troponin and elevated B-type natriuretic peptide in serum of affected patients portends an adverse prognosis. Management strategies for cardiac amyloid are largely based on nonrandomized single-center studies. One of the few published randomized studies shows the superiority of oral prednisolone and melphalan compared with colchicine in systemic AL amyloidosis. Intermediate-dose infusional chemotherapy regimes (such as vincristine, adriamycin, and dexamethasone) and high-dose chemotherapy with peripheral stem cell rescue have been used widely, but treatment-related mortality remains substantial with chemotherapy. Recent studies also indicate promising strategies to stabilize the native structures of amyloidogenic proteins; inhibit fibril formation; and disrupt established deposits using antibodies, synthetic peptides, and small-molecule drugs.     

Evaluation and management of the cardiac amyloidosis.

Cardiac amyloidosis describes clinically significant involvement of the heart by amyloid deposition, which may or may not be associated with involvement of other organs. The purpose of this review is to summarize the current state of evidence for the effective evaluation and management of cardiac amyloidosis. Acquired systemic amyloidosis occurs in more than 10 per million person-years in the U.S. population. Although no single noninvasive test or abnormality is pathognomonic of cardiac amyloid, case-control studies indicate that echocardiographic evidence of left ventricular wall thickening, biatrial enlargement, and increased echogenicity in conjunction with reduced electrocardiographic voltages is strongly suggestive of cardiac amyloidosis. Furthermore, newer echocardiographic techniques such as strain and strain rate imaging can demonstrate impairment in longitudinal function before ejection fraction becomes abnormal. Recent observational studies also suggest that cardiovascular magnetic resonance imaging yields characteristic findings in amyloidosis, offering promise for the early detection of cardiac involvement, and the presence of detectable cardiac troponin and elevated B-type natriuretic peptide in serum of affected patients portends an adverse prognosis. Management strategies for cardiac amyloid are largely based on nonrandomized single-center studies. One of the few published randomized studies shows the superiority of oral prednisolone and melphalan compared with colchicine in systemic AL amyloidosis. Intermediate-dose infusional chemotherapy regimes (such as vincristine, adriamycin, and dexamethasone) and high-dose chemotherapy with peripheral stem cell rescue have been used widely, but treatment-related mortality remains substantial with chemotherapy. Recent studies also indicate promising strategies to stabilize the native structures of amyloidogenic proteins; inhibit fibril formation; and disrupt established deposits using antibodies, synthetic peptides, and small-molecule drugs.     

Clinical experience with cardiac amyloidosis

OBJECTIVE: Amyloidosis is a systemic disease potentially afflicting the heart. In this study we retrospectively studied patients presenting with major cardiac amyloidotic involvement. METHODS AND RESULTS: From 1997 until 2000, eight patients with major cardiac involvement of amyloidosis resulting in heart failure were diagnosed. All patients presented with heart failure. Diagnostic work-up, clinical, electrocardiographic, echocardiographic characteristics and treatment modalities are presented. Seven patients with acquired (both primary AL and postinflammatory AA) amyloidosis out of a total of eight patients died within one year after diagnosis, as a result of intractable cardiac failure due to both systolic and diastolic left ventricular dysfunction despite state-of-the-art medical treatment of heart failure. Only one patient with hereditary amyloidosis undergoing liver transplantation survived. CONCLUSIONS: Despite optimal medical cardiac failure treatment, acquired cardiac amyloidosis carries an ominous prognosis probably because patients are already in a very advanced stage of the disease at presentation.     

Plasma hepatocyte growth factor is a novel marker of AL cardiac amyloidosis

Abstract

Background: Cardiac amyloidosis is an infiltrative cardiomyopathy that is challenging to diagnose. We hypothesized that the novel biomarkers hepatocyte growth factor (HGF), galectin-3 (GAL-3), interleukin-6 (IL-6), and vascular endothelial growth factor (VEGF) would be elevated in cardiac amyloidosis and may be able to discriminate from non-cardiac systemic amyloidosis or other cardiomyopathies with similar clinical or morphologic characteristics.

Methods: Patients were selected from the Vanderbilt Main Heart Registry according to the following groups: (1) amyloid light-chain (AL) cardiac amyloidosis (n?=?26); (2) transthyretin (ATTR) cardiac amyloidosis (n?=?7); (3) left ventricular hypertrophy (LVH) (n?=?45); (4) systolic heart failure (n?=?42); and (5) non-cardiac systemic amyloidosis (n?=?7). Biomarkers were measured in stored plasma samples. Biomarkers' discrimination performance in predicting AL cardiac amyloidosis (i.e., Concordance index) was reported. A survival analysis was used to explore the relationship between HGF levels and mortality among AL cardiac amyloidosis patients.

Results: HGF levels were markedly elevated in patients with AL cardiac amyloidosis (median?=?622, interquartile range (IQR): 299–1228?pg/mL) compared with the other groups, including those with non-cardiac systemic amyloidosis (median?=?134, IQR: 94–163?pg/mL, p?<?0.001). HGF was not a specific marker for ATTR amyloidosis. Gal-3 was elevated in all groups with amyloidosis but could not differentiate between those with and without cardiac involvement. There was no difference in IL-6 or VEGF between those with AL cardiac amyloidosis compared to other groups (p?=?0.13 and 0.057, respectively).

Conclusions: HGF may be a specific marker that distinguishes AL cardiac amyloidosis from other cardiomyopathies with similar clinical or morphologic characteristics. Further studies are necessary to determine whether HGF levels predict the likelihood of survival.     

Is technetium-99 m-pyrophosphate scintigraphy valuable in the diagnosis of cardiac amyloidosis?

Amyloidosis is a systemic disease frequently involving the myocardium and leading to functional disturbances of the heart. Amyloidosis can mimic other cardiac diseases. A conclusive clinical diagnosis of cardiac involvement can only be made by a combination of different diagnostic methods. In 7 patients with myocardial amyloidosis we used a combined first-pass and static scintigraphy with technetium-99 m-pyrophosphate. There was only insignificant myocardial uptake of the tracer. The first-pass studies however revealed reduced systolic function in 4/7 patients and impaired diastolic function in 6/7 patients. Therefore, although cardiac amyloid could not be demonstrated in the static scintigraphy due to amyloid fibril amount and composition, myocardial functional abnormalities were seen in the first-pass study.     

How to Identify Transthyretin Cardiac Amyloidosis at an Early Stage

Cardiac involvement of systemic amyloidosis is preferentially observed in patients with amyloid light chain amyloidosis or transthyretin amyloidosis (ATTR). Owing to the development of diagnostic modalities and changes in recognition by physicians, transthyretin cardiac amyloidosis (ATTR-CA) is now understood to be a more common cause of heart failure than previously thought. Recent progress in disease-modifying therapeutic interventions, such as transthyretin stabilizers, has resulted in ATTR-CA changing from an incurable disease to a curable disease. These interventions are particularly effective in patients with mild symptoms of heart failure, thus indicating that early detection and a precise diagnosis are important for improving the prognosis. In this review article, we summarize the recent reports of early screening of ATTR-CA and describe some important points regarding the making of a precise diagnosis, especially focusing on histological evaluations.     

An Unusual Case of Cardiac Amyloidosis

Cardiac amyloidosis can result from any of the systemic amyloidoses. The disease is often characterized by a restrictive cardiomyopathy although the particular signs and symptoms depend in part on the underlying cause. In addition to managing the symptoms of heart failure, treatment options vary depending on the etiology of amyloid deposition. It is therefore critical to identify the cause of cardiac amyloidosis before initiating definitive therapy. We present a patient with presumed immunoglobulin (AL) amyloidosis who had a circulating lambda monoclonal protein, but a bone marrow biopsy with kappa predominant plasma cells. This unusual finding called into question the diagnosis of AL amyloidosis and highlights the importance and difficulty of determining the cause of cardiac amyloid deposition before initiating treatment. We review the different forms of cardiac amyloidosis and propose a diagnostic algorithm to help identify the etiology of cardiac amyloid deposition before beginning therapy.