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Cardiovascular Diagnosis and Therapy Dec 2023Cardiac amyloidosis (CA) is one of the causes of heart failure with preserved ejection fraction. Cardiac magnetic resonance (CMR) with late gadolinium enhancement (LGE)...
BACKGROUND
Cardiac amyloidosis (CA) is one of the causes of heart failure with preserved ejection fraction. Cardiac magnetic resonance (CMR) with late gadolinium enhancement (LGE) and extracellular volume (ECV) fractions is a preferred method to identify CA. However, the requirement of contrast limits its use in renal deficiency patients. Myocardial strain is a promising method without contrast. We sought to assess the early diagnostic and prognostic value of strain.
METHODS
This retrospective study enrolled 31 patients with systemic amyloidosis (SA) in Peking University First Hospital from January 2014 to January 2019. The patients were categorized into three groups, including 11 CA patients with left ventricular hypertrophy (CA-LVH group), 9 CA patients without LVH (CA-NLVH group), and 11 patients with extracardiac SA (SA group). Strain analysis was performed with CMR images. A least absolute shrinkage and selection operator (LASSO) was used to generate strain score. The receiver operating characteristic (ROC) curve was used to evaluate the early diagnostic efficacy of strain score and other single strain parameter. The primary endpoint was defined as death from all cause or rehospitalization for heart failure. A Cox proportional hazards model was used to assess the index value on the prognosis.
RESULTS
In CA patients, as the left ventricular wall thickens, the global and regional strain decrease significantly. A new strain score (strain score = 0.00893 × mid-septal circumferential peak strain + 0.02285 × apical radial peak strain + 0.1541 × apical circumferential peak strain + 0.33097 × epicardial circumferential average peak strain + 0.42232 × endocardial longitudinal average peak strain) generated using LASSO showed that the area under the ROC curve was 0.909. All the patients with outcome events were in CA groups, four were in CA-LVH group and one in CA-NLVH group. New York Heart Association (NYHA) grade [hazard ratio (HR) =14.29, 95% confidence interval (CI): 2.34-87.34, P<0.01], brain natriuretic peptide (HR =20.05, 95% CI: 2.21-182.36, P=0.008), cardiac injury biomarker (HR =11.59, 95% CI: 1.03-130.36, P=0.047), E/E' (mitral inflow to mitral relaxation velocity ratio) (HR =1.09, 95% CI: 1.00-1.18, P=0.040), end-systolic left ventricular volume (HR =1.04, 95% CI: 1.00-1.18, P=0.039) and LGE volume (HR =1.11, 95% CI: 1.02-1.20, P=0.012) positively correlate with events. Better renal function (HR =0.92, 95% CI: 0.86-0.98, P=0.011) and ejection fraction (HR =0.94, 95% CI: 0.88-0.99, P=0.027) appear to be protective factors. Although with no statistical difference, the strain damage had a tendency to predict poor prognosis, i.e., mid-ventricular circumferential strain with HR of 1.25 (95% CI: 1.0-1.57, P=0.050) and strain score with HR of 1.30 (95% CI: 0.98-1.73, P=0.067).
CONCLUSIONS
Myocardial strain decreased in CA patients. The integrated magnetic resonance imaging (MRI) strain score can serve as a useful tool to identify early myocardial involvement in amyloidosis. The strain damage had a tendency to predict poor prognosis.
PubMed: 38162105
DOI: 10.21037/cdt-23-205 -
Journal of Clinical and Experimental... 2023To clarify the significance of bone marrow fibrosis and amyloid deposition in plasma cell neoplasm, a retrospective cross-sectional study for a period of 3 years was...
To clarify the significance of bone marrow fibrosis and amyloid deposition in plasma cell neoplasm, a retrospective cross-sectional study for a period of 3 years was conducted. Patients who underwent bone marrow aspiration and biopsy with suspicion of plasma cell neoplasms were included in the study. The bone marrow findings were correlated with clinical profile of the patient along with biochemical parameters, cytogenetics, Fluorescent in situ hybridization (FISH) wherever available. A total of 273 bone marrow aspirates and biopsies of patients with suspected plasma cell neoplasms were analyzed. There were 181 male patients and 92 female patients (Male: Female = 1.96: 1). There were 245 cases of multiple myeloma (89.7%), 8 cases of primary amyloidosis (2.9%) and 6 monoclonal gammopathy of undetermined significance (MGUS) (2.1%), 5 cases of plasmacytoma (1.8%) and 4 cases of smouldering myeloma (1.4%), 5 cases of POEMS syndrome (1.8%). Bone marrow fibrosis was noted in 12 patients at diagnosis (4.3%). Among the parameters studied, only the mean Hemoglobin was significantly low in patients with marrow fibrosis. Amyloid deposition in various organs including bone marrow, kidney, liver etc., were noted in 17 patients overall (6.2%). In conclusion, the incidence of fibrosis (4.3%) and amyloidosis (6.2%) associated with plasma cell neoplasms were much lower in our study as compared to published studies.
Topics: Humans; Male; Female; Multiple Myeloma; Plasmacytoma; Primary Myelofibrosis; In Situ Hybridization, Fluorescence; Retrospective Studies; Cross-Sectional Studies; Plasma Cells
PubMed: 38148011
DOI: 10.3960/jslrt.23029 -
Chinese Medical Journal Jan 2024
Topics: Humans; Consensus; Immunoglobulin Light-chain Amyloidosis; Heart; Immunoglobulin Light Chains; China
PubMed: 38146261
DOI: 10.1097/CM9.0000000000002961 -
Journal of Clinical Medicine Dec 2023Amyloid deposits can be the cause of many chronic diseases. Primary localized cutaneous amyloidosis (PLCA) is a chronic dermatologic condition with amyloid deposits in...
Amyloid deposits can be the cause of many chronic diseases. Primary localized cutaneous amyloidosis (PLCA) is a chronic dermatologic condition with amyloid deposits in the papillary dermis. The most common types of the keratinocyte-derived form of PLCA include macular (MA), lichen (LA), and biphasic (BA) amyloidosis. The estimated prevalence of PLCA in the Asian population is 0.98/10,000, which is higher than in the European population; thus, epidemiologic data on PLCA in the Caucasian population are limited. We performed a retrospective single-center study analyzing epidemiologic characteristics of a Central European PLCA population. Epidemiologic data regarding age, sex, skin phototype (Fitzpatrick scale I-VI), disease duration, comorbidities, history of atopy, and family history of PLCA were collected. Clinical characteristics, localization of PLCA lesions, applied therapies and treatment outcomes were also analyzed. Dermoscopic characteristics were also evaluated. A total of 41 patients diagnosed with PLCA were included, with 22 presenting with macular, 18 with lichen, and 1 with biphasic amyloidosis. The male/female ratio was 16/25, and mean age at diagnosis was 54.6 ± 15.2 years (range 27-87 years). The mean age at the onset of PLCA was 53 ± 16.1 years (range 19-79 years) in MA, 46.7 ± 18.2 years (range 14-73 years) in LA, and 26 years in BA. The interscapular region in MA and the extensor surface of the lower extremities in LA proved to be localization-related areas. In our center, a wide range of therapeutic options was applied, with the most prescribed being topical corticosteroids in all types of PLCA. We presented a retrospective, monocentric study on the epidemiology of PLCA in the Central European region. By examining the medical data of a significant number of PLCA patients, we compared our epidemiologic data with that of the Asian PLCA population. Due to the rarity of the condition, further randomized controlled trials and guidelines are needed to improve therapeutic outcomes.
PubMed: 38137741
DOI: 10.3390/jcm12247672 -
Cells Dec 2023Human body cells are stem cell (SC) derivatives originating from bone marrow. Their special characteristics include their capacity to support the formation and... (Review)
Review
Human body cells are stem cell (SC) derivatives originating from bone marrow. Their special characteristics include their capacity to support the formation and self-repair of the cells. Cancer cells multiply uncontrollably and invade healthy tissues, making stem cell transplants a viable option for cancer patients undergoing high-dose chemotherapy (HDC). When chemotherapy is used at very high doses to eradicate all cancer cells from aggressive tumors, blood-forming cells and leukocytes are either completely or partially destroyed. Autologous stem cell transplantation (ASCT) is necessary for patients in those circumstances. The patients who undergo autologous transplants receive their own stem cells (SCs). The transplanted stem cells first come into contact with the bone marrow and then undergo engraftment, before differentiating into blood cells. ASCT is one of the most significant and innovative strategies for treating diseases. Here we focus on the treatment of Hodgkin's lymphoma, non-Hodgkin's lymphoma, multiple myeloma, and AL amyloidosis, using ASCT. This review provides a comprehensive picture of the effectiveness and the safety of ASCT as a therapeutic approach for these diseases, based on the currently available evidence.
Topics: Humans; Hematopoietic Stem Cell Transplantation; Multiple Myeloma; Immunoglobulin Light-chain Amyloidosis; Transplantation, Autologous; Lymphoma, Non-Hodgkin; Stem Cell Transplantation
PubMed: 38132175
DOI: 10.3390/cells12242855 -
Turk Patoloji Dergisi 2024Cardiac amyloidosis is a type of amyloidosis that deserves special attention as organ involvement significantly worsens the prognosis. Cardiac amyloidosis can be grouped...
Cardiac amyloidosis is a type of amyloidosis that deserves special attention as organ involvement significantly worsens the prognosis. Cardiac amyloidosis can be grouped under three main headings: immunoglobulin light chain (AL) amyloidosis that is dependent on amyloidogenic monoclonal light chain production; hereditary Transthyretin (TTR) amyloidosis that results from accumulation of mutated TTR; and wild-type (non-hereditary) TTR amyloidosis formerly known as senile amyloidosis. Although all three types cause morbidity and mortality due to severe heart failure when untreated, they contain differences in their pathogenesis, clinical findings, and treatment. In this article, the clinical features, pathogenesis, diagnosis, and treatment methods of cardiac amyloidosis will be explained with an overview, and an awareness will be raised in the diagnosis of this disease.
Topics: Humans; Cardiomyopathies; Amyloidosis; Prognosis; Immunoglobulin Light Chains
PubMed: 38111336
DOI: 10.5146/tjpath.2023.12923 -
Colombia Medica (Cali, Colombia) 2023Amyloid light chain (AL) amyloidosis is characterized by amyloid fibril deposition derived from monoclonal immunoglobulin light chains, resulting in multiorgan...
BACKGROUND
Amyloid light chain (AL) amyloidosis is characterized by amyloid fibril deposition derived from monoclonal immunoglobulin light chains, resulting in multiorgan dysfunction. Limited data exist on the clinical features of AL amyloidosis.
OBJECTIVE
This study aims to describe the clinical characteristics, treatments, and outcomes in Colombian patients with AL amyloidosis.
METHODS
A retrospective descriptive study was conducted at three high-complexity centers in Medellín, Colombia. Adults with AL amyloidosis diagnosed between 2012 and 2022 were included. Clinical, laboratory, histological, treatment, and survival data were analyzed.
RESULTS
The study included 63 patients. Renal involvement was most prevalent (66%), followed by cardiac involvement (61%). Multiorgan involvement occurred in 61% of patients. Amyloid deposition was most commonly detected in renal biopsy (40%). Bortezomib-based therapy was used in 68%, and 23.8% received high-dose chemotherapy with autologous hematopoietic stem cell transplantation (HDCT-ASCT). Hematological response was observed in 95% of patients with available data. Cardiac and renal organ responses were 15% and 14%, respectively. Median overall survival was 45.1 months (95% CI: 22.2-63.8). In multivariate analysis, cardiac involvement was significantly associated with inferior overall survival (HR 3.27; 95% CI: 1.23-8.73; =0.018), HDCT-ASCT had a non-significant trend towards improved overall survival (HR 0.25; 95% CI: 0.06-1.09; =0.065).
CONCLUSIONS
In this study of Colombian patients with AL amyloidosis, renal involvement was more frequent than cardiac involvement. Overall survival and multiorgan involvement were consistent with data from other regions of the world. Multivariate analysis identified cardiac involvement and HDCT-AHCT as possible prognostic factors.
Topics: Adult; Humans; Immunoglobulin Light-chain Amyloidosis; Colombia; Retrospective Studies; Treatment Outcome; Bortezomib
PubMed: 38107838
DOI: 10.25100/cm.v54i3.5667 -
Therapeutic Advances in Cardiovascular... 2023Cardiac amyloidosis (CA) is a condition caused by extracellular deposition of amyloid fibrils in the heart. It is an underdiagnosed disease entity which can present with... (Review)
Review
Cardiac amyloidosis (CA) is a condition caused by extracellular deposition of amyloid fibrils in the heart. It is an underdiagnosed disease entity which can present with a variety of cardiac and non-cardiac manifestations. Diagnosis usually follows an initial suspicion based on clinical evaluation or imaging findings before confirmation with subsequent imaging (echocardiography, cardiac magnetic resonance imaging, 3,3-diphosphono-1,2-propanodicarboxylic acid scintigraphy) in combination with biochemical screening for monoclonal dyscrasia (serum free light chains and serum and urine electrophoresis) and/or histology (bone marrow trephine, fat or endomyocardial biopsy). More than 95% of CA can be classified as either amyloid light-chain (AL) CA or amyloid transthyretin (ATTR) CA; these two conditions have very different management strategies. AL-CA, which may be associated with multiple myeloma, can be managed with chemotherapy agents, autologous stem cell transplantation, cardiac transplant and supportive therapies. For ATTR-CA, there is increasing importance in making an early diagnosis because of novel treatments in development, which have transformed this once incurable disease to a potentially treatable disease. Timely diagnosis is crucial as there may only be a small window of opportunity where patients can benefit from treatment beyond which therapies may be less effective. Reviewing the existing patient pathway provides a basis to better understand the complexities of real-world activities which may be important to help reduce missed opportunities related to diagnosis and treatment for patients with CA. With healthcare provider interest in improving the care of patients with CA, the development of an optimal care pathway for the condition may help reduce delays in diagnosis and treatment and thus enhance patient outcomes.
Topics: Humans; Cardiomyopathies; Hematopoietic Stem Cell Transplantation; Transplantation, Autologous; Amyloidosis; Immunoglobulin Light-chain Amyloidosis; Echocardiography; Amyloid; Early Diagnosis; Amyloidogenic Proteins
PubMed: 38099406
DOI: 10.1177/17539447231216318 -
Journal of Clinical Medicine Dec 2023(1) Background: To evaluate the predictive value of Holter monitoring for overall survival (OS) of patients with light chain amyloidosis (AL amyloidosis). (2) Methods:...
(1) Background: To evaluate the predictive value of Holter monitoring for overall survival (OS) of patients with light chain amyloidosis (AL amyloidosis). (2) Methods: 137 patients with newly diagnosed AL amyloidosis who underwent Holter monitoring within 6 months of diagnosis were included. The primary outcome was OS. Landmark analysis was conducted at one-year follow-up. Independent predictors were determined using the log-rank test and multivariate Cox regression analysis. (3) Results: 131 (95.6%) patients received non-transplant therapy, and 32 (23.4%) underwent daratumumab-based chemotherapy. After a median follow-up of 20.3 months, 47 deaths occurred. Atrial tachycardia (AT), conduction delay, and non-sustained ventricular tachycardia (NSVT) were associated with poor OS one year beyond diagnosis in univariate analyses (patients with vs. without AT: 57.3% [95% confidence interval (CI): 47.2-67.4] vs. 81.0% (95% CI: 74.8-87.2), = 0.039; patients with vs. without NSVT: 33.3% (95% CI: 8.5-58.1) vs. 75.3% (95% CI: 69.8-80.8), = 0.024; patients with vs. without conduction delay: 41.7% (95% CI: 24.4-59.0) vs. 75.4% (95% CI: 69.7-81.1), = 0.003]. AT [hazard ratio (HR): 2.6; 95% CI: 1.0-6.5; = 0.049) and conduction delay (HR: 4.3; 95% CI: 1.3-14.3; = 0.016) were independent predictors of OS after accounting for age and 2012 Mayo stage. (4) Conclusion: AT and conduction delay in Holter monitoring are independent predictors of poor OS one year beyond diagnosis in AL amyloidosis.
PubMed: 38068514
DOI: 10.3390/jcm12237457 -
Nature Communications Dec 2023Overexpression of antibody light chains in small plasma cell clones can lead to misfolding and aggregation. On the other hand, the formation of amyloid fibrils from...
Overexpression of antibody light chains in small plasma cell clones can lead to misfolding and aggregation. On the other hand, the formation of amyloid fibrils from antibody light chains is related to amyloidosis. Although aggregation of antibody light chain is an important issue, atomic-level structural examinations of antibody light chain aggregates are sparse. In this study, we present an antibody light chain that maintains an equilibrium between its monomeric and tetrameric states. According to data from X-ray crystallography, thermodynamic and kinetic measurements, as well as theoretical studies, this antibody light chain engages in 3D domain swapping within its variable region. Here, a pair of domain-swapped dimers creates a tetramer through hydrophobic interactions, facilitating the revelation of the domain-swapped structure. The negative cotton effect linked to the β-sheet structure, observed around 215 nm in the circular dichroism (CD) spectrum of the tetrameric variable region, is more pronounced than that of the monomer. This suggests that the monomer contains less β-sheet structures and exhibits greater flexibility than the tetramer in solution. These findings not only clarify the domain-swapped structure of the antibody light chain but also contribute to controlling antibody quality and advancing the development of future molecular recognition agents and drugs.
Topics: Humans; Immunoglobulin Light Chains; Amyloid; Crystallography, X-Ray; Amyloidosis; Thermodynamics
PubMed: 38065949
DOI: 10.1038/s41467-023-43443-4