Abstract 15635: Myocardial Function Index Predicts Mortality in Amyloid Light Chain Cardiomyopathy

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Nadia S Akhiyat ◽  
Vidhu Anand ◽  
Alexander Ryu ◽  
Vinayak Kumar ◽  
Barry A Borlaug ◽  
...  
Keyword(s):  
Light Chain ◽  
Myocardial Function ◽  
Cox Model ◽  
Univariate Analysis ◽  
Extracellular Volume ◽  
Blood Pool ◽  
Myocardial Contraction ◽  
Al Amyloidosis ◽  
Function Index ◽  
Amyloid Light Chain

Introduction: Cardiovascular disease remains the leading cause of morbidity and mortality in patients with amyloid light chain (AL) amyloidosis. Current prognostic evaluation in AL cardiomyopathy (AL-CM) largely relies upon disparate proxy measurements to assess mortality. With respect to observed myocardial volume changes between systole and diastole, we describe a single measurement derived from cardiac MRI (CMR) to assess mortality of AL-CM. Methods: A cohort of 129 consecutive patients with AL-CM undergoing CMR with amyloid protocol from the years 2001 - 1997 was reviewed. Myocardial volume change at end systole and end diastole was assessed by disc summation with CMR. The myocardial function index (MFI) was calculated by consolidating blood pool and myocardial volume measures as confluent components of myocardial function utilizing operator tracings. The association of MFI and death was assessed with adjusted hazard ratios (HR) derived by a Cox model. Results: Data at time of CMR was reviewed. The mean age was 60 ±10; 68% subjects were female. Median survival from CMR was 47 months. Mean LVEF was assessed by echocardiography to be 55% ± 12. Mean calculated MFI was 19.8% ±7. Univariate analysis suggested MFI is strongly associated with death (HR 0.004; 95%CI 0.00002-0.0838; p = 0.0003). A multivariate analysis re-demonstrated the strong predictive value of MFI when controlled for age (HR 0.006; 95%CI 0.00003 - 0.1156; p = 0.0006). Conclusion: MFI strongly correlates with mortality in AL-CM. In contrast to previously described assessments of ventricular function (extracellular volume imaging, myocardial perfusion imaging, and myocardial contraction fraction), MFI is easily derived from CMR and considers blood pool and myocardial volumes as confluent components of myocardial function. Further studies are needed to assess MFI amongst patients with varying etiologies of heart failure.

scholarly journals Role of different hematologic variables in defining the risk of malignant transformation in monoclonal gammopathy

Blood ◽  
1996 ◽  
Vol 87 (3) ◽  
pp. 912-918 ◽  
Author(s):  
L Baldini ◽  
A Guffanti ◽  
BM Cesana ◽  
M Colombi ◽  
O Chiorboli ◽  
...  
Keyword(s):  
Malignant Transformation ◽  
Light Chain ◽  
Monoclonal Gammopathy ◽  
Cox Model ◽  
Univariate Analysis ◽  
Cost Benefit ◽  
Cumulative Probability ◽  
Relative Risks ◽  
Monoclonal Component

The presenting clinico-hematologic features of 386 patients with nonmyelomatous monoclonal gammopathy (MG) were correlated with the frequency of malignant transformation to evaluate the most important variables conditioning its evolution into multiple myeloma (MM) or Waldenstrom macroglobulinemia (WM). Most of the patients (335) had monoclonal gammopathy of undetermined significance (MGUS: 39 IgA, 242 IgG, 54 IgM): the remaining 51 patients (12 IgA, 39 IgG) fulfilled all of the MGUS diagnostic criteria (according to Durie) except that bone marrow plasma cell (BMPC) content was 10% to 30%, and so they were defined as having monoclonal gammopathy of borderline significance (MGBS). There were no significant differences between the MGUS and MGBS groups in terms of age, sex, or median follow-up. After a median follow- up of 70 and 53 months, respectively, 23 of 335 MGUS and 19 of 51 MGBS patients had undergone a malignant evolution. Univariate analysis of the IgA and IgG patients showed that the cumulative probability of the disease evolving into MM correlated with diagnostic definition (MGBS v MGUS), BMPC content (> or = 10% v < 5% and < or = 5% v > 5%) and reduced serum polyclonal Ig. In the IgG cases, there was also a significant correlation with detectable Bence Jones proteinuria, serum monoclonal component (MC) levels and age at diagnosis (> 70 v < = or 55 years). In the IgG cases as a whole, the same variables remained in the Cox model where the BMPC percentage was considered after natural logarithmic transformation and the monoclonal component as g/dL value. The relative risks of developing MM are the following: 2.4 for each 1 g/dL increase of IgG, serum MC, 3.5 for detectable light chain proteinuria, 4.4 for the increase of 1 unit in log. BMPC percentage, 6.1 for age > 70, 3.6 and 13.1 for a reduction in one or two polyclonal Ig. In conclusion, our study allows the identification of a particular subset of MGUS patients (MC < = or 1.5 g/dL, BMPC < 5%, no reduction in polyclonal Ig and no detectable light chain proteinuria) at very low- risk of evolution, who can be considered as having benign monoclonal gammopathies. We also describe a previously undefined group of MG patients (with monoclonal gammopathy of borderline significance) who are at high-risk of malignant evolution. These findings could have a considerable impact on the cost/benefit ratio of monitoring programs in these patients.

scholarly journals Immunoglobulin Light-Chain Amyloidosis: From Basics to New Developments in Diagnosis, Prognosis and Therapy

2016 ◽  
Vol 135 (3) ◽  
pp. 172-190 ◽  
Author(s):  
Eli Muchtar ◽  
Francis K. Buadi ◽  
Angela Dispenzieri ◽  
Morie A. Gertz
Keyword(s):  
Light Chain ◽  
Plasma Cells ◽  
Treatment Options ◽  
Organ Damage ◽  
Major Effect ◽  
Response To Treatment ◽  
Al Amyloidosis ◽  
Prognostic Effect ◽  
Amyloid Light Chain ◽  
Immunoglobulin Light Chain Amyloidosis

Immunoglobulin amyloid light-chain (AL) amyloidosis is the most common form of systemic amyloidosis, where the culprit amyloidogenic protein is immunoglobulin light chains produced by marrow clonal plasma cells. AL amyloidosis is an infrequent disease, and since presentation is variable and often nonspecific, diagnosis is often delayed. This results in cumulative organ damage and has a negative prognostic effect. AL amyloidosis can also be challenging on the diagnostic level, especially when demonstration of Congo red-positive tissue is not readily obtained. Since as many as 31 known amyloidogenic proteins have been identified to date, determination of the amyloid type is required. While several typing methods are available, mass spectrometry has become the gold standard for amyloid typing. Upon confirming the diagnosis of amyloidosis, a pursuit for organ involvement is essential, with a focus on heart involvement, even in the absence of suggestive symptoms for involvement, as this has both prognostic and treatment implications. Details regarding initial treatment options, including stem cell transplantation, are provided in this review. AL amyloidosis management requires a multidisciplinary approach with careful patient monitoring, as organ impairment has a major effect on morbidity and treatment tolerability until a response to treatment is achieved and recovery emerges.

scholarly journals A case of isolated amyloid light-chain amyloidosis of the radial nerve

2016 ◽  
Vol 125 (3) ◽  
pp. 598-602 ◽  
Author(s):  
Ron Ron Cheng ◽  
Ramin Eskandari ◽  
Cynthia T. Welsh ◽  
Abhay K. Varma
Keyword(s):  
Peripheral Nerve ◽  
Light Chain ◽  
Radial Nerve ◽  
Systemic Disease ◽  
Mass Spectrometry Analysis ◽  
Al Amyloidosis ◽  
Electrodiagnostic Testing ◽  
Nerve Involvement ◽  
Peripheral Nerve Involvement ◽  
Amyloid Light Chain

Peripheral nerve involvement may be the first sign of systemic amyloid light-chain (AL) amyloidosis, a rare disease. Physical examination and electrodiagnostic testing are the mainstays of peripheral neuropathy evaluation at presentation. Sural nerve biopsy is performed in conjunction with serum and urine protein evaluation to differentiate between focal and systemic disease. Systemic disease is treated with a combination of chemotherapy, steroids, and stem cell transplantation. Isolated peripheral nerve disease is extremely rare. The authors here report the case of an 80-year-old woman who presented with progressive right upper-extremity weakness due to right radial neuropathy discovered upon electrodiagnostic testing. Magnetic resonance neurography (MRN) revealed a focal lesion within the right radial nerve. She underwent radial nerve exploration and excision of an intraneural mass consisting of amyloid on histopathology, with mass spectrometry analysis diagnostic for AL amyloidosis. Noninvasive testing and clinical history did not suggest systemic involvement. This unique case of isolated peripheral nerve AL amyloidosis in the absence of signs and symptoms of systemic disease is described, and the literature demonstrating peripheral nerve involvement in AL amyloidosis is reviewed.

Acquired factor X deficiency in patients with amyloid light-chain amyloidosis: incidence, bleeding manifestations, and response to high-dose chemotherapy

Blood ◽  
2001 ◽  
Vol 97 (6) ◽  
pp. 1885-1887 ◽  
Author(s):  
Elie B. Choufani ◽  
Vaishali Sanchorawala ◽  
Timothy Ernst ◽  
Karen Quillen ◽  
Martha Skinner ◽  
...  
Keyword(s):  
Light Chain ◽  
Medical Center ◽  
Bleeding Complications ◽  
Plasma Cell Dyscrasia ◽  
High Dose ◽  
Al Amyloidosis ◽  
Related Factor ◽  
Factor X ◽  
Factor X Deficiency ◽  
Amyloid Light Chain

Acquired deficiency of factor X occurs in patients with systemic amyloid light-chain (AL) amyloidosis, presumably due to adsorption of factor X to amyloid fibrils. Of 368 consecutive patients with systemic AL amyloidosis evaluated at Boston Medical Center, 32 patients (8.7%) had factor X levels below 50% of normal. Eighteen of these patients (56%) had bleeding complications, which were more frequent and severe in the 12 patients below 25% of normal; 2 episodes were fatal. Ten factor X–deficient patients received high-dose melphalan chemotherapy followed by autologous stem cell transplantation. Of 7 patients alive 1 year after treatment, 4 had a complete hematologic response, and all 4 experienced improvement in their factor X levels. One of 2 additional patients with partial hematologic responses had improvement in factor X. Thus, aggressive treatment of the underlying plasma cell dyscrasia in AL amyloidosis can lead to the amelioration of amyloid-related factor X deficiency.

scholarly journals Electrocardiogram Characteristics and Prognostic Value in Light-Chain Amyloidosis: A Comparison With Cardiac Magnetic Resonance Imaging

2021 ◽  
Vol 8 ◽  
Author(s):  
Xinli Guo ◽  
Zhian Chen ◽  
Ke Wan ◽  
Rizhen Song ◽  
Tingjie Yang ◽  
...  
Keyword(s):  
Cardiac Magnetic Resonance ◽  
Magnetic Resonance ◽  
Light Chain ◽  
Prognostic Value ◽  
Cox Regression ◽  
Extracellular Volume ◽  
Al Amyloidosis ◽  
Amyloid Burden ◽  
Light Chain Amyloidosis ◽  
Fragmented Qrs

Background: An electrocardiogram (ECG) is a simple and cheap non-invasive tool that shows various abnormalities and has prognostic value for patients with light-chain amyloidosis (AL). The present study aimed to explore the association between ECG characteristics and cardiac magnetic resonance (CMR)-detected amyloid burden and to investigate the prognostic value of ECG in AL amyloidosis.Methods: We prospectively enrolled 99 patients with AL amyloidosis (56 male patients; median age, 58 y). Detailed clinical information, 12-lead ECG, and CMR data were collected. All patients were followed up longitudinally, and the endpoint was all-cause mortality. ECG characteristics were analyzed and correlated with the degree of late gadolinium enhancement (LGE) and extracellular volume (ECV) by T1 mapping on CMR. The prognostic value of ECG characteristics was analyzed using Kaplan–Meier survival analysis and multivariate Cox regression.Results: During a median follow-up period of 33 months, 69 of the 99 patients died. Fragmented Q wave-R wave-S wave (QRS), pathological Q waves, the Sokolow index, QRS duration, and voltages were significantly associated with the extent of LGE, native T1, and ECV by CMR (p &lt; 0.05). Fragmented QRS and Sokolow index showed independent prognostic value in AL amyloidosis (p = 0.001; p = 0.026, respectively). Fragmented QRS remained independent after adjusting for clinical values (hazard ratio: 2.034; 95% confidence interval: 1.148–3.603; p = 0.015). However, no ECG characteristics were independent predictors for prognosis in AL amyloidosis when LGE and ECV were included in the multivariate analysis.Conclusion: ECG abnormalities showed significant association with CMR indicators of amyloid burden. Fragmented QRS has an independent prognostic value in AL amyloidosis and could be used as an alternative marker when CMR is not available.

scholarly journals A comparison of immunohistochemistry and mass spectrometry for determining light chain amyloid fibril protein from formalin-fixed renal biopsy tissue in a single Chinese center

2019 ◽  
Author(s):  
Ying Sun ◽  
Jian Sun ◽  
Wei Sun ◽  
Junyi Pang ◽  
Yubing Wen ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Renal Biopsy ◽  
Light Chain ◽  
Protein Identification ◽  
Amyloid Fibrils ◽  
Al Amyloidosis ◽  
Precise Diagnosis ◽  
Ffpe Tissues ◽  
Amyloid Light Chain ◽  
Formalin Fixed

Abstract Background Amyloidosis, a disease caused by abnormal protein deposition in tissues, is classified according to the protein precursor that form amyloid fibrils. Diagnosis of amyloidosis is type-specific as the identification of amyloid protein determines the following treatment. However, around a quarter of amyloidosis cases cannot be accurately subtyped by most commonly used immunohistochemistry (IHC). In order to obtain precise diagnosis, our study is focusing on another protein identification methods, laser microdissection and mass spectrometry (LDMS). Methods 20 cases of Amyloid Light-chain (AL) amyloidosis without further subtype were included. IHC and LDMS were used to detect light chains on formalin-fixed paraffin-embedded (FFPE) tissues from renal biopsy. Results 100% consistence between positive IHC and LDMS results were observed, however, chances of subtyping using LDMS is increased to 94% compared to IHC which is only 76%. Conclusion LDMS is a valuable tool in regard to subtyping amyloidosis.

scholarly journals Dissecting the Molecular Features of Systemic Light Chain (AL) Amyloidosis: Contributions from Proteomics

Medicina ◽  
2021 ◽  
Vol 57 (9) ◽  
pp. 916
Author(s):  
Paola Rognoni ◽  
Giulia Mazzini ◽  
Serena Caminito ◽  
Giovanni Palladini ◽  
Francesca Lavatelli
Keyword(s):  
Light Chain ◽  
Amyloid Fibrils ◽  
Cell Clone ◽  
Experimental Models ◽  
Critical Discussion ◽  
Al Amyloidosis ◽  
Primary Role ◽  
Molecular Features ◽  
Amyloid Light Chain ◽  
Models Of Disease

Amyloidoses are characterized by aggregation of proteins into highly ordered amyloid fibrils, which deposit in the extracellular space of tissues, leading to organ dysfunction. In AL (amyloid light chain) amyloidosis, the most common form in Western countries, the amyloidogenic precursor is a misfolding-prone immunoglobulin light chain (LC), which, in the systemic form, is produced in excess by a plasma cell clone and transported to target organs though blood. Due to the primary role that proteins play in the pathogenesis of amyloidoses, mass spectrometry (MS)-based proteomic studies have gained an established position in the clinical management and research of these diseases. In AL amyloidosis, in particular, proteomics has provided important contributions for characterizing the precursor light chain, the composition of the amyloid deposits and the mechanisms of proteotoxicity in target organ cells and experimental models of disease. This review will provide an overview of the major achievements of proteomic studies in AL amyloidosis, with a presentation of the most recent acquisitions and a critical discussion of open issues and ongoing trends.

scholarly journals Multiorgan involvement by amyloid light chain amyloidosis

2019 ◽  
Vol 47 (4) ◽  
pp. 1778-1786 ◽  
Author(s):  
Guoliang Li ◽  
Dan Han ◽  
Suhua Wei ◽  
Huaiyu Wang ◽  
Limei Chen
Keyword(s):  
Light Chain ◽  
Amyloid Fibrils ◽  
Normal Structure ◽  
Al Amyloidosis ◽  
Initial Symptom ◽  
Close Monitoring ◽  
Clinical Complexity ◽  
Amyloid Light Chain ◽  
Low Incidence ◽  
Chemotherapy Strategy

Amyloid light chain (AL) amyloidosis is a protein conformational disease. AL amyloidosis results from aggregation of misfolded proteins that are deposited in tissues as amyloid fibrils. Diagnosis of AL amyloidosis can be challenging due to its low incidence and clinical complexity. Therapy requires a risk-adapted approach involving dose reductions and schedule modifications of chemotherapy regimens along with close monitoring of hematologic and organ responses. We herein describe a patient whose condition was diagnosed as systemic AL amyloidosis and presented with splenic rupture as the initial symptom. Congo red staining of the kidney biopsy was positive. The normal structure of the liver and spleen had been replaced by amyloid deposition. The chemotherapy strategy involved a combination of bortezomib, cyclophosphamide, thalidomide, and dexamethasone.

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