Senile systemic amyloidosis presenting as bilateral carpal tunnel syndrome

A 74-year-old woman who had developed numbness in both hands was diagnosed as having bilateral carpal and right cubital tunnel syndrome and underwent bilateral carpal and right cubital tunnel release. Transthyretin immunoreactive amyloid deposits were seen on specimens and were also detected in gastric, duodenal and ileal mucosal biopsies. The transthyretin gene analysis showed no mutation. This is a rare case of senile systemic amyloidosis presenting as carpal tunnel syndrome.     

Transthyretin valine-94-alanine,a novel variant associated with late-onset systemic amyloidosis with cardiac involvement

A 63-year-old Caucasian male, diagnosed with dilated cardiomyopathy in 1993, remained clinically stable for several years. In 2003, a marked increase of N-terminal pro-natriuretic peptide serum level (611 ng/ml to 4926 ng/ml) was observed; left ventricular (LV) septum thickness was 10 mm. In addition, sensorimotor polyneuropathy and autonomic dysfunction occurred. Further progression of heart failure occurred despite unchanged systolic LV function. Endomyocardial biopsy in 2006 revealed transthyretin amyloidosis by Congo red and immunohistochemical staining, as well as Val94Ala substitution by transthyretin gene analysis. Cardiac amyloid deposition was quantified by technetium-99m-3,3-diphosphono-1,2-propanodicarboxylic acid (^99mTc-DPD) scintigraphy. Mutational search of the relatives (n = 1) was unremarkable. The transthyretin Val94Ala mutation is characterized by sensorimotor polyneuropathy, autonomic dysfunction, and gastrointestinal and cardiac involvement with amyloid. This mutation is an addition to the growing spectrum of transthyretin mutations with late onset of clinical symptoms, but noteworthy because of progressive, finally disabling disease course. Final clinical assessment of severity of cardiac involvement in the present patient is rendered complex by possible concomitant or preceding idiopathic dilated cardiomyopathy.     

Prevalence of cardiac amyloidosis among elderly patients with systolic heart failure or conduction disorders

Objective: Cardiac amyloid infiltration can lead to systolic heart failure (HF) or to conduction disorders (CD). Patients with transthyretin (ATTR) amyloidosis are particularly exposed. We sought to determine the prevalence of ATTR and AL among patients >60?years admitted with CD or unexplained systolic HF and increased wall thickness.

Materials and Methods: We studied 143 patients (57% males, 79?±?9?years) with HF (N?=?28) or CD requiring pacemaker implantation (N?=?115). In total, 139 (97%) patients (28 with HF and 111 with CD) underwent ^99mTc-DPD scintigraphy to detect ATTR, and 105 (73%; 19 HF and 86?CD) underwent AL screening.

Results: Five patients (4%; 95%CI:0–7%) exhibited wild-type ATTR (ATTRwt) amyloidosis, 2 (2%; 95%CI:0–4%) had CD and 3 (11%; 95%CI:0–23%) HF. No patient showed AL. The 2 ATTRwt patients with CD were previously asymptomatic, did not show classical ECG signs and exhibited mild LV hypertrophy with preserved LVEF. By contrast, all ATTRwt patients with HF had ECG and echocardiographic signs of amyloid. During a mean follow-up of 18?±?11?months, 3(60%) patients with ATTRwt amyloidosis (1?CD and 2 HF) and 14(10.4%) without died.

Conclusion: Prevalence of ATTRwt amyloidosis in patients with CD requiring pacemaker is low. Although, additional studies are needed, prevalence seems to be higher in elderly patients with systolic HF.     

Early diagnosis and management of patients with familial ATTR amyloidosis receiving livers from asymptomatic variant TTR carriers

The possibility of a with familial ATTR amyloidosis patient receiving a liver from an asymptomatic variant TTR carrier is remote. However, in 2008, it was reported that this unlikely event occurred in a patient in Portugal. We report our protocol for early diagnosis and management of this entity.     

Diagnostic score for the detection of cardiac amyloidosis in patients with left ventricular hypertrophy and impact on prognosis

Background: Among diagnosis associated with left ventricular hypertrophy (LVH), cardiac amyloidosis (CA) is a progressive disease with poor prognosis. Early noninvasive identification is of growing clinical importance. The objective of our study was to integrate clinical, biologic, electrocardiographic and echocardiographic parameters to build a diagnostic score in patients with LVH.

Methods and results: One hundred and fourteen patients with LVH underwent a cardiac magnetic resonance (CMR) and a ^99mTc-hydroxymethylene-diphosphonate scintigraphy (^99mTc-HMDP) allowing to discriminate three groups of diagnoses: CA (n?=?50 including 31, 18 and 1 ATTR, AL and AA amyloidosis), hypertrophic cardiomyopathy (n?=?19) and unspecific cardiomyopathy (n?=?45). Seven continuous variables associated with CA (systolic arterial pressure <130?mmHg; PR duration >200?ms; Sokolow index <12?mV; diastolic left ventricular posterior thickness >13?mm; E/Ea ratio >10; global longitudinal strain?>??12% and sum of basal longitudinal strain?>??47%) were selected and dichotomized according to the best cutoff value to build the diagnostic score, which was validated in an independent cohort of 34 patients with LVH from aortic stenosis. The area under the ROC curve for the diagnosis of CA using the score was 0.933 (95%CI 0.889–0.978). The best cut off value for the score was 3 leading to a sensitivity of 90% and specificity of 81%. Area under the ROC curve for the score was 0.932 in the validation cohort. A diagnostic score >3 was associated with a poorest prognosis.

Conclusion: An integrated evaluation of 6 diagnostic factors including arterial blood pressure, ECG and echocardiographic parameters to build a diagnostic score is a simple and easily method to discriminate the 3 main CA in patients with LVH.     

Serum levels of NT-proBNP as surrogate for cardiac amyloid burden: new evidence from gadolinium-enhanced cardiac magnetic resonance imaging in patients with amyloidosis

Background.?The prognostic value of NT-proBNP has been recognized in patients with amyloidosis complicated by cardiac involvement. We aimed to use contrast enhanced cardiac magnetic resonance imaging (CMR) to identify functional and structural alterations related to levels of NT-proBNP better to understand the mechanisms of its release in cardiac amyloidosis.

Methods and Results.?CMR was performed on a 1.5-T scanner in 34 patients with biopsy proven amyloid light chain (AL; n?=?27) or hereditary transthyretin related (TTR; n?=?7) amyloidosis. NT-proBNP was higher in patients with (n?=?25) compared to patients without cardiac involvement (n?=?9) (2931 (IQR: 972–8629; min-max: 25–27,277) pg/ml vs. 177 (IQR: 71–1431; min-max: 22–7935) pg/ml, p?=?0.008). ROC analysis identified a NT-proBNP of <2426.5?pg/ml as optimal discriminator for event free survival (682?±?65 days). NT-proBNP did not correlate with LV- ejection fraction, end-diastolic and end-systolic volumes or stroke volume. There was a moderate correlation between NT-proBNP and LV-mass (R?=?0.52, p?=?0.003) and extent of late gadolinium enhancement (LGE; R?=?0.41, p?=?0.04).

Conclusions.?This study confirms the prognostic value of NT-proBNP in patients with AL and TTR amyloidosis and provides the novel finding that NT-proBNP correlates with surrogates of myocardial amyloid burden such as LV-mass and LGE, supporting the concept of NT-proBNP as a biomarker reflecting the severity of cardiac amyloid infiltration.     

心肌淀粉样变性临床特点及远期预后的影响因素

目的探讨心肌淀粉样变性患者的临床特点及其远期预后的影响因素。方法回顾性分析119例临床确诊心肌淀粉样变性患者的临床资料,电话随访患者的生存状态,分析患者的临床表现、心电图、心脏超声及心脏磁共振特点及其与远期预后的关系,主要观测终点为全因死亡。应用SPSS 17.0统计软件进行数据分析。结果 119例患者首发症状多样,以气短喘憋和胸闷为主,其次为下肢水肿和乏力,心功能多为美国纽约心脏病学会心功能分级Ⅲ～Ⅳ级。患者1年生存率50%,5年生存率仅为25%,全因死亡率的独立影响因素包括脑利钠肽前体(NT-proBNP)、肌钙蛋白T、糖抗原125(CA125)、白蛋白、血氯、免疫球蛋白M水平。结论心肌淀粉样变性患者预后差,1年生存率仅为50%。患者全因死亡率的独立影响因素包括NT-proBNP、肌钙蛋白T、CA125、白蛋白、血氯、免疫球蛋白M水平。     

肥厚型心肌病患者心源性猝死风险的识别及预防

肥厚型心肌病(HCM)是一种遗传性心肌病,大多数HCM患者一生中出现的症状都很轻微。然而,HCM患者有发生室性心律失常和心源性猝死(SCD)的风险,在中国成年人中其患病率为80/10万,且SCD是HCM最严重的并发症。识别HCM患者发生SCD的风险,可以改善预后结局。本文结合当前指南及近年来HCM与SCD方面的相关研究,对HCM患者发生SCD的病理机制、风险因素的识别及预防进行综述。     

Prognostic significance of late gadolinium enhancement on cardiac magnetic resonance in patients with hypertrophic cardiomyopathy

Background

Late gadolinium enhancement (LGE) on cardiac MRI indicates the myocardial fibrosis in hypertrophic cardiomyopathy (HCM), and the prognostic value of LGE in HCM has been described in several studies, but controversy exists given the limited power of these studies to predict future adverse cardiac events. The objective of this study was to perform a meta-analysis to systematically evaluate the predictive value of LGE on cardiac magnetic resonance (CMR) for future adverse cardiac events.

Sudden cardiac death in patients with hypertrophic cardiomyopathy: From bench to bedside with an emphasis on genetic markers

Hypertrophic cardiomyopathy (HCM) is the most common cause of death in the young, particularly in young competitive athletes. Death often occurs suddenly in asymptomatic, apparently healthy individuals. Several clinical parameters as well as genetic factors have been characterized that can identify those HCM patients who are at high risk for sudden cardiac death (SCD). The clinical parameters that have some predictive values for SCD in HCM patients are the following: a prior history of SCD, a family history of SCD, history of syncope, symptomatic ventricular tachycardia on Holter monitoring, inducible ventricular tachycardia during electrophysiologic studies, and myocardial ischemia in children with HCM. Recent identification of mutations in the beta myosin heavy chain gene and genotype-phenotype correlation in HCM patients have shown that the beta myosin heavy chain mutations are also prognosticators in HCM families. Several mutations such as Arg⁴⁰³Gln and Arg⁷¹⁹Gln are associated with a high incidence of SCD, while Leu⁹⁰⁸Val mutation is associated with a benign course and a low incidence of SCD in HCM families. Additional genetic factors such as a polymorphism in angiotensin-converting enzyme I gene may also contribute to a high incidence of SCD in HCM families. Identification and characterization of HCM patients at high risk for SCD provide the opportunity to render prophylactic therapeutic interventions, such as implantation of defibrillators, in these individuals.     

Collagen remodeling and cardiac dysfunction in patients with hypertrophic cardiomyopathy: the significance of type III and VI collagens

BACKGROUND: The relationship between the extent of myocardial interstitial fibrosis, the percentage of each type of collagen, and cardiac function in patients with hypertrophic cardiomyopathy (HC) has not been established. HYPOTHESIS: The study aimed to establish that increases in some types of collagen may correlate with cardiac dysfunction. METHODS: Mallory-Azan staining and immunohistochemical staining by the avidin-biotin-complex (ABC) method using anticollagen antibodies were performed on the myocardial biopsy specimens in 35 patients with HC, and the percentage and type of collagen present was determined. Left ventricular (LV) function was evaluated by cardiac catheterization and ventriculography. RESULTS: The percentage of myocardial interstitial fibrosis correlated highly with indices of LV diastolic and systolic function. The amount of type III collagen correlated significantly with the peak negative dp/dt, the rapid filling volume/stroke volume, and the ejection fraction (EF). Significant correlations also were noted between the amount of type VI collagen and peak negative dp/dt, peak positive dp/dt, and EF. Type I collagen did not correlate with any of the LV function indices, and type IV collagen correlated only with peak ejection rate. Type V collagen did not accumulate substantially in the myocardial interstitium. CONCLUSIONS: The progression of myocardial interstitial fibrosis in the HC heart adversely impacts both the diastolic and systolic function of the LV. Increases in the percentage of type III and VI collagen correlate with cardiac dysfunction.     

肥厚型梗阻性心肌病经酒精室间隔消融术后心脏结构及功能变化

目的 探讨经皮穿刺腔内酒精室间隔心肌消融术（percutaneous transluminal alcohol septal myocardial ablation,PTSMA）对肥厚型梗阻性心肌病（hypertrophic obstructive cardiomyopathy,HOCM）患者心脏结构及功能的影响.方法 收集2006年1月至2012年12月在成都市第三人民医院住院的HOCM患者24例,比较其PTSMA术前、术后3个月及术后12个月的左心室流出道压力阶差、室间隔厚度、左心室后壁厚度、左心房内径、左心室舒张末期内径、纽约心脏病协会（NYHA）心功能分级、左心室射血分数和左心室短轴缩短率的变化.结果 HOCM患者进行PTSMA术后3个月及术后12个月左心室流出道压力阶差、室间隔厚度、左心室后壁厚度、左心房内径、左心室舒张末期内径、纽约心脏病协会心功能分级、左心室射血分数和左心室短轴缩短率与术前比较,差异有统计学意义（P＜0.05）;术后12个月相比术后3个月,以上指标变化差异无统计学意义（P＞0.05）.结论 PTSMA能显著改善HOCM患者左心室流出道梗阻及降低室壁厚度,改善患者心功能,是有效的治疗方法.     

Inducibility of life-threatening ventricular arrhythmias is related to maximum left ventricular thickness and clinical markers of sudden cardiac death in patients with hypertrophic cardiomyopathy attributable to the Asp175Asn mutation in the alpha-tropomyosin gene

We investigated inducibility of life-threatening arrhythmias with programmed ventricular stimulation (PVS) in relation to clinical markers of sudden cardiac death (SCD) in subjects with hypertrophic cardiomyopathy (HCM) attributable to the Asp175Asn mutation in the α-tropomyosin gene (TPM1-Asp175Asn). PVS was performed with up to three extrastimuli and distribution of markers of SCD was evaluated in 21 adult subjects with the TPM1-Asp175Asn. Sustained polymorphic ventricular tachycardia (VT) or ventricular fibrillation (VF) was induced in seven of 21 subjects (33%). Inducible subjects had more severe left ventricular hypertrophy (LVH) and an increased number of markers of SCD (family history of SCD, syncope or presyncope, fall in systolic blood pressure (BP) during exercise, documented non-sustained VT (NSVT), and marked LVH) compared to non-inducible subjects (IVS 2.4 ± 0.3 cm vs. 1.6 ± 0.5 cm, P < 0.001; and two to three vs. one to two markers of SCD, P = 0.007, respectively). In conclusion, in HCM attributable to the Asp175Asn mutation in the α-tropomyosin gene, life-threatening arrhythmias were induced in one third of the patients. Inducibility was associated with the maximum left ventricular (LV) thickness and the number of markers of SCD, suggesting that in HCM patients with an identical causative mutation, susceptibility to ventricular arrhythmias is related to the cardiomyopathic phenotype.