High sensitivity cardiac troponin T in patients with immunoglobulin light chain amyloidosis

Heart ◽  
2014 ◽  
Vol 100 (5) ◽  
pp. 383-388 ◽  
Author(s):  
A Dispenzieri ◽  
M A Gertz ◽  
S K Kumar ◽  
M Q Lacy ◽  
R A Kyle ◽  
...  
Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2887-2887 ◽  
Author(s):  
Angela Dispenzieri ◽  
Morie A Gertz ◽  
Amy K Saenger ◽  
Martha Grogan ◽  
Shaji Kumar ◽  
...  

Abstract Abstract 2887 Introduction: Cardiac involvement is the major cause of death in patients with immunoglobulin light chain amyloidosis (AL). Detection of cardiac involvement and risk stratification has been facilitated by cardiac biomarkers like troponin T (cTnT) and N-terminal brain natriuretic peptide (NT-proBNP). A novel high sensitivity cTnT (hs-cTnT) assay has been developed, and we evaluated its diagnostic use with three questions in mind: 1) How do the cTnT and hs-cTnT perform in the AL amyloid staging system? 2) Does higher sensitivity add significant additional value in terms of prognosticating outcomes for patients with AL amyloidosis? 3) Can the current AL amyloidosis staging system be further improved upon? Methods: Stored serum samples (-20°C) from 224 pts with AL were analyzed for concentrations of hsTnT, TnT, and NT-proBNP on the E170 Modular analyzer (Roche Diagnostics, Penzberg, Germany). 99th percentile reference limits were <0.014 and <0.010 mcg/L for hsTnT and TnT, respectively. Results: Median values for hsTnT, TnT, and NT-proBNP were 38 ng/L (range 0–075.4), 0.017 mcg/L (<0.0–0.904), and 1230 ng/L (0–32, 226), respectively. The correlation coefficient between hsTnT and TnT was 0.972. Those classified by echocardiographic parameters as having (n=143) or not having (n=81) cardiac involvement had TnT concentrations of 0.04 and 0.01 mcg/L and hsTnT levels of 52.2 and 15.6 ng/L, respectively. The direct numeric result from the hs-cTnT result CANNOT merely be substituted for a cTnT result in the Mayo AL staging system since 14% of patients would be misclassified. The performance of the receiver operation curve derived hs-cTnT cut-point of 54 ng/L is a slight improvement over the direct substitution of 35 ng/L if replacement of one assay for another is required. An alternate staging option using hs-cTnT alone—using the two thresholds14 ng/L and 54 ng/L (figure)—performs as well as either the original Mayo AL staging system or a derivative system incorporating hs-cTnT with respective relative risks of death (95%CI) of 3.6 (2.3, 5.7), 3.8 (2.5, 5.9), and 3.3 (2.2, .50). On multivariate analysis, our newly described alternate 3 level, hs-cTnT alone staging system is independent of other factors including period of diagnosis, type of therapy, and NT-proBNP value, the last of which dropped out of the model. Alternate models using NT-proBNP and cTnT were explored, but none performed better than the original staging system or the new hs-cTnT system. Conclusion: The direct numeric result from the hs-cTnT result cannot merely be substituted for a cTnT result in the Mayo amyloid staging system. Consideration could be made for AL staging systems using hs-cTnT alone and relegating the NT-proBNP for measuring cardiac response. Disclosures: Jaffe: Roche: Consultancy.


2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Linchun Xu ◽  
Yongzhong Su

AbstractImmunoglobulin light chain amyloidosis (AL) is an indolent plasma cell disorder characterized by free immunoglobulin light chain (FLC) misfolding and amyloid fibril deposition. The cytogenetic pattern of AL shows profound similarity with that of other plasma cell disorders but harbors distinct features. AL can be classified into two primary subtypes: non-hyperdiploidy and hyperdiploidy. Non-hyperdiploidy usually involves immunoglobulin heavy chain translocations, and t(11;14) is the hallmark of this disease. T(11;14) is associated with low plasma cell count but high FLC level and displays distinct response outcomes to different treatment modalities. Hyperdiploidy is associated with plasmacytosis and subclone formation, and it generally confers a neutral or inferior prognostic outcome. Other chromosome abnormalities and driver gene mutations are considered as secondary cytogenetic aberrations that occur during disease evolution. These genetic aberrations contribute to the proliferation of plasma cells, which secrete excess FLC for amyloid deposition. Other genetic factors, such as specific usage of immunoglobulin light chain germline genes and light chain somatic mutations, also play an essential role in amyloid fibril deposition in AL. This paper will propose a framework of AL classification based on genetic aberrations and discuss the amyloid formation of AL from a genetic aspect.


Author(s):  
Chen Dongxu ◽  
Zhou Yannan ◽  
Yang Yilin ◽  
Yao Chenling ◽  
Gu Guorong ◽  
...  

Abstract Objectives A rapid 0 h/1 h algorithm using high-sensitivity cardiac troponin T (hs-cTnT) for rule-out and rule-in of non-ST-segment elevation myocardial infarction (NSTEMI) is recommended by the European Society of Cardiology. We aim to prospectively evaluate the diagnostic performance of the algorithm in Chinese Han patients with suspected NSTEMI. Methods In this prospective diagnostic cohort study, 577 patients presenting to the emergency department with suspected NSTEMI and recent (<12 h) onset of symptoms were enrolled. The levels of serum hs-cTnT were measured on admission, 1 h later and 4–14 h later. All patients underwent the initial clinical assessment and were triaged into three groups (rule-out, rule-in and observe) according to the 0 h/1 h algorithm. The major cardiovascular events (MACE) were evaluated at the 7-day and 30-day follow-ups. Results Among 577 enrolled patients, NSTEMI was the final diagnosis for 106 (18.4%) patients. Based on the hs-cTnT 0 h/1 h algorithm, 148 patients (25.6%) were classified as rule-out, 278 patients (48.2%) as rule-in and 151 patients (26.2%) were assigned to the observe group. The rule-out approach resulted in a sensitivity of 100% and negative predictive value of 100%. The rule-in approach resulted in a specificity of 62.9% [95% CI (58.5–67.2%)] and positive predictive value of 37.1% [95%CI (31.3–42.8%)]. No MACE was observed in the rule-out group within 30-day follow-up. Conclusions The hs-cTnT 0 h/1 h algorithm is a safe tool for early rule-out of NSTEMI, while probably not an effective strategy for accurate rule-in of NSTEMI in Chinese Han population.


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