natriuretic-peptide--brain and Immunoglobulin-Light-chain-Amyloidosis

Severity of cardiac involvement remains the leading determinant of survival in light chain (AL) amyloidosis. Until recently, cardiac response after treatment relied on reduction of N-terminal pro-brain natriuretic peptide (NT-proBNP). In this study, 94 patients with AL amyloidosis (baseline BNP ≥150 pg/ml) had BNP measured at 6 months following treatment. Median overall survival was not reached for cardiac response (≥50 pg/ml and ≥ 30% decrease in BNP), 9·2 years for cardiac stability (<50 pg/ml and <30% change in BNP) and 2·8 years for cardiac progression (≥50 pg/ml or ≥30% increase in BNP) (log-rank P < 0·001). Cardiac response and progression, as measured by BNP values, are significantly associated with survival in AL amyloidosis.

Topics: Aged; Disease-Free Survival; Female; Follow-Up Studies; Humans; Immunoglobulin Light-chain Amyloidosis; Male; Middle Aged; Myocardium; Natriuretic Peptide, Brain; Survival Rate

As cardiac involvement is the most important prognostic marker in light-chain amyloidosis (AL), revised Mayo staging for AL incorporated N-terminal pro-brain natriuretic peptide (NTproBNP) and troponin T (TnT). However, prognostic value of novel biomarkers, such as soluble suppression of tumorigenicity 2 (sST2), growth differentiation factor 15 (GDF15), or osteopontin (OPN) is unknown in AL amyloidosis. We aimed to investigate additive predictive effects of novel biomarkers for overall mortality rates of AL amyloidosis patients. Levels of sST2, GDF15, and OPN were quantified at diagnosis in a total of 73 AL amyloidosis patients at Samsung Medical Center from 2010 to 2016. The median follow-up duration of the censored cases was 18.0 (12.4-28.1) months. A total of 25 deaths occurred during the follow-up period. Two novel biomarkers, sST2 and GDF-15 showed satisfactory predictive performances for both one-year and overall survival from ROC analysis. Best cut-off values for predicting one-year mortality were selected. Elevated sST2 and GDF-15 levels showed significant incremental prognostic values in addition to NT-ProBNP and TnT for overall mortality. Patients were assigned 1 point for elevated sST2 or GDF-15. The mean values of NT-proBNP, TnT, mean LV wall thickness, and septal e' velocity differed significantly according to the scores. Patients with higher scores showed significantly worse prognosis even in patients with advanced revised Mayo staging. Two novel biomarkers, sST2 and GDF-15, showed satisfactory prognostic value for overall survival of AL amyloidosis patients. Furthermore, sST2 and GDF-15 showed additive incremental values over conventional biomarkers and further discriminated prognosis of patients in advanced stages.

Topics: Aged; Biomarkers; Disease-Free Survival; Female; Follow-Up Studies; Growth Differentiation Factor 15; Humans; Immunoglobulin Light-chain Amyloidosis; Interleukin-1 Receptor-Like 1 Protein; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Survival Rate; Troponin T

We retrospectively reviewed the utility of N-terminal prohormone of brain natriuretic peptide (NT-proBNP) and transthoracic echocardiogram (TTE) in diagnosing cardiac involvement in patients with biopsy-proven systemic immunoglobulin light chain amyloidosis seen at the Mayo Clinic between 1 January 2006 and 30 December 2015. We analyzed 2 cohorts: patients undergoing endomyocardial biopsy for suspicion of cardiac involvement (cohort 1) and patients who had serum NT-proBNP and comprehensive echocardiographic evaluation at diagnosis (cohort 2). Of 179 patients undergoing endomyocardial biopsy (cohort 1), 173 (97%) had evidence of amyloid deposition, with 159 having NT-proBNP performed at the time of the procedure. The NT-proBNP was elevated (>300 pg/mL) in all 159 patients (sensitivity, 100%; median NT-proBNP, 4917 pg/mL; range, 355-69 541). The left ventricular ejection fraction, interventricular septal thickness, and strain rate were abnormal in 89/168 (53%), 102/64 (61%) and 92/95 (97%), respectively. Among cohort 2 (n = 342), 259 (76%) had an elevated NT-proBNP, of whom 237 (92%) had an abnormality detected on TTE. Of 83 patients with normal NT-proBNP <300 pg/mL, 27 (33%) had an abnormality on TTE (all with borderline strain rate -18% to -15%). Only 5/27 patients were considered to have possible early cardiac involvement and none had any other diagnostic or classical features of amyloidosis on TTE. The combination of NT-proBNP and comprehensive echocardiographic evaluation can diagnose cardiac amyloidosis negating the need for endomyocardial biopsy. A negative NT-proBNP rules out clinically meaningful cardiac involvement and may obviate the routine use of TTE in patients with a low clinical suspicion of cardiac amyloidosis.

Topics: Adult; Aged; Aged, 80 and over; Echocardiography; Female; Heart Diseases; Humans; Immunoglobulin Light-chain Amyloidosis; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Retrospective Studies; Stroke Volume; Ventricular Function, Left

Cardiac involvement in systemic amyloidosis (AL) occurs in ~50% of all AL patients. However once symptomatic heart failure develops, therapeutic options are limited thereby conferring a poor overall prognosis. The median survival is <6 months when AL patients are untreated for the underlying plasma cell dyscrasia. We thus sought to identify risk factors of increased mortality in treatment-naïve, AL cardiac amyloidosis with heart failure. Patients with biopsy-proven AL cardiac amyloid, who presented with heart failure and did not received prior AL treatment, were enrolled between 2004-2014, at the initial visit to the Amyloidosis Center at Boston University Medical Center. Routine laboratory tests, physical examination and echocardiography data were collected. There were 165 predominantly white (76.4%), and male (61%) patients, with a mean age of 61.6 ± 9.5 years. Median survival was 10.9 months (95% CI 6.2-14.7). By multivariate analysis increased relative wall thickness (RWT) [HR 6.70; 95% CI 2.45-18.30), older age (HR 1.04; 95% CI 1.01-1.06), higher New York Heart Association (NYHA) functional class (HR 1.50; 95% CI 1.02-2.2), log brain natriuretic peptide (BNP) levels (HR 1.45; 95% CI 1.15-1.81) and C-reactive protein (CRP) levels (HR 1.02; 95% CI 1.00-1.04) were significant predictors for increased mortality. In conclusion, in treatment-naïve, AL cardiac amyloidosis patients with heart failure symptoms who lack these high-risk features may have a better outcome. These findings might allow for better risk stratification although outcomes are still poor.

Topics: Aged; Biomarkers; C-Reactive Protein; Disease-Free Survival; Echocardiography; Female; Heart Failure; Humans; Immunoglobulin Light-chain Amyloidosis; Male; Middle Aged; Natriuretic Peptide, Brain; Survival Rate

In Ig light chain (AL) amyloidosis, cardiac involvement is associated with worse prognosis and increased treatment-related complications. In this retrospective cohort study, we assessed survival, hematologic and cardiac responses to high-dose melphalan and auto-SCT (HDM/SCT) in patients with AL amyloidosis and cardiac involvement, stratified by cardiac biomarkers brain natriuretic peptide and Troponin I, analogous to the Mayo cardiac staging. Forty-seven patients underwent HDM/SCT based upon functional measures; six patients had modified cardiac stage I disease, seventeen had modified cardiac stage II disease and twenty-four had modified cardiac stage III disease. Treatment-related mortality was 4% for all patients and 8% for patients with stage III disease. Three-year survival was 88% and EFS was 47%; these did not differ by stage. By intention-to-treat analysis, 27% of patients achieved a hematologic complete response and 32% a very good partial response, of whom 70 and 45%, respectively, have not required additional therapy at 36 months. Cardiac response was achieved in 53% of patients. We conclude that with appropriate patient selection and a risk-adapted treatment approach, HDM/SCT is safe and effective in patients with AL amyloidosis and cardiac involvement.

Topics: Aged; Amyloidosis; Biomarkers; Female; Follow-Up Studies; Heart Diseases; Hematopoietic Stem Cells; Humans; Immunoglobulin Light-chain Amyloidosis; Kaplan-Meier Estimate; Male; Melphalan; Middle Aged; Natriuretic Peptide, Brain; Prognosis; Proportional Hazards Models; Retrospective Studies; Stem Cell Transplantation; Time Factors; Treatment Outcome; Troponin I

In systemic light-chain (AL) amyloidosis, cardiac involvement is a major determinant of survival; however, cardiac response is limited even after systemic treatment in a majority of patients, and some require heart transplantation. Additionally, limited information is available on specific indications for heart transplantation. We aimed to explore clinical outcomes of cardiac amyloidosis and its association with heart transplantation, including identifying factors favoring heart transplantation amenability.. We retrospectively analyzed data from patients diagnosed with AL amyloidosis with cardiac involvement between January 2007 and December 2020 at a tertiary referral center.. Among 73 patients, 72 (99%) received systemic treatment, and 12 (16%) underwent heart transplantation. Characteristics at diagnosis were similar between heart transplant recipients and nonrecipients, although left ventricular ejection fraction tended to be lower in recipients (median 48% versus 57%, P  = 0.085). Eight weeks after systemic treatment, 67% and 12% of patients achieved hematologic and brain natriuretic peptide responses. Overall survival was longer among heart transplantation recipients than nonrecipients, with 5-y survival rates of 61.1% (95% confidence interval, 25.5%-83.8%) versus 32.0% (95% confidence interval, 20.3%-44.4%; P  = 0.022), respectively. Among the 34 with identifiable causes of death out of 51 deaths, 21 nonrecipients (62%) died of cardiac problems compared with none in the heart transplant recipients. Additionally, survival outcomes favored heart transplant recipients in most subgroups, including patients with higher Mayo 2004 European stage at diagnosis and with extracardiac involvement of amyloidosis.. Heart transplantation can achieve long-term survival in appropriately selected patients with AL cardiac amyloidosis.

Topics: Amyloidosis; Heart Transplantation; Humans; Immunoglobulin Light-chain Amyloidosis; Natriuretic Peptide, Brain; Retrospective Studies; Stroke Volume; Ventricular Function, Left

Cardiac light chain amyloidosis (AL-CA) patients often die within three months of starting chemotherapy. Chemotherapy for non-immunoglobulin M gammopathy with AL-CA frequently includes bortezomib (Bor), cyclophosphamide (Cy), and dexamethasone (D). We previously reported that NT-ProBNP levels can double within 24h of dexamethasone administration, suggesting a deleterious impact on cardiac function. In this study, we evaluate the role of dexamethasone in early cardiovascular mortality during treatment.. We retrospectively assessed 100 de novo cardiac AL patients (62% male, mean age 68 years) treated at our institute between 2009 and 2018 following three chemotherapy regimens: CyBorDComb (all initiated on day 1; 34 patients), DCyBorSeq (D, day 1; Cy, day 8; Bor, day 15; 17 patients), and CyBorDSeq (Cy, day 1; Bor, day 8; D, day 15; 49 patients). The primary endpoint was cardiovascular mortality and cardiac transplantation at days 22 and 455. At day 22, mortality was 20.6% with CyBorDComb, 23.5% with DCyBorSeq, and 0% with CyBorDSeq (p = 0.003). At day 455, mortality was not significantly different between regimens (p = 0.195). Acute toxicity of dexamethasone was evaluated on myocardial function using a rat model of isolated perfused heart. Administration of dexamethasone induced a decrease in left ventricular myocardium contractility and relaxation (p<0.05), supporting a potential negative inotropic effect of dexamethasone in AL-CA patients with severe cardiac involvement.. Delaying dexamethasone during the first chemotherapy cycle reduces the number of early deaths without extending survival. It is clear that dexamethasone is beneficial in the long-term treatment of patients with AL-CA. However, the initial introduction of dexamethasone during treatment is critical, but may be associated with early cardiac deaths in severe CA. Thus, it is important to consider the dosage and timing of dexamethasone introduction on a patient-severity basis. The impact of dexamethasone in the treatment of AL-CA needs further investigation.

Topics: Aged; Animals; Antineoplastic Combined Chemotherapy Protocols; Bortezomib; Cyclophosphamide; Dexamethasone; Female; Heart Diseases; Heart Transplantation; Humans; Immunoglobulin Light-chain Amyloidosis; Male; Middle Aged; Multiple Myeloma; Myocardial Contraction; Natriuretic Peptide, Brain; Peptide Fragments; Perfusion; Rats; Rats, Wistar; Retrospective Studies; Troponin T; Ventricular Dysfunction, Left

Topics: Adult; Aged; Aged, 80 and over; Bortezomib; Disease-Free Survival; Female; Humans; Immunoglobulin Light Chains; Immunoglobulin Light-chain Amyloidosis; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments

Timely recognition of cardiac amyloidosis is clinically important, but the diagnosis is frequently delayed.. We sought to identify a multi-modality approach with the highest diagnostic accuracy in patients evaluated by cardiac biopsy, the diagnostic gold standard.. Consecutive patients (N = 242) who underwent cardiac biopsy for suspected amyloidosis within an 18-year period were retrospectively identified. Cardiac biomarker, ECG, and echocardiography results were examined for correlation with biopsy-proven disease. A prediction model for cardiac amyloidosis was derived using multivariable logistic regression.. Among patients with an advanced infiltrative cardiomyopathy phenotype, traditional biomarker, ECG, and echocardiography-based screening tests have limited individual diagnostic utility for cardiac amyloidosis. A prediction algorithm including age, relative wall thickness, E/e', and low limb lead voltage improves the detection of cardiac biopsy-proven disease.

Topics: Age Factors; Aged; Amyloid Neuropathies, Familial; Amyloidosis; Biopsy; Blood Flow Velocity; Cardiomyopathies; Clinical Decision Rules; Echocardiography; Electrocardiography; Female; Heart Ventricles; Humans; Immunoglobulin Light-chain Amyloidosis; Logistic Models; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Organ Size; Sex Factors; Troponin I

Light-chain (AL) amyloidosis is the most common type of systemic amyloidosis with poor prognosis. Currently, the predictors of cardiac involvement and prognostic staging systems are primarily based on conventional echocardiography and serological biomarkers. We used three-dimensional speckle tracking echocardiography (STE-3D) measurements of strain, hypothesizing that it could detect cardiac involvement and aid in prediction of mortality.. We retrospectively analysed 74 consecutive patients with biopsy-proven AL amyloidosis. Among them, 42 showed possible cardiac involvement and 32 without cardiac involvement. LV global longitudinal strain (GLS), global radial strain, global circumferential strain and global area strain (GAS) measurements were obtained.. The GLS and GAS were considered significant predictors of cardiac involvement. The cut-off values discriminating cardiac involvement were 16.10% for GLS, 32.95% for GAS. During the median follow-up of 12.5 months (interquartile range 4-25 months), 20 (27%) patients died. For the Cox proportional model survival analysis, heart rate, cardiac troponin T, NT-proBNP levels, E/e', GLS, and GAS were univariate predictors of death. Multivariate Cox model showed that GLS ≤ 14.78% and cardiac troponin T ≥ 0.049 mg/l levels were independent predictors of survival.. STE-3D measurements of LV myocardial mechanics could detect cardiac involvement in patients with AL amyloidosis; GLS and cardiac biomarkers can provided prognostic information for mortality prediction.

Topics: Aged; Biomarkers; Cardiomyopathies; Disease Progression; Echocardiography, Three-Dimensional; Female; Humans; Immunoglobulin Light-chain Amyloidosis; Male; Middle Aged; Myocardial Contraction; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Retrospective Studies; Risk Assessment; Risk Factors; Time Factors; Troponin T; Ventricular Function, Left

Topics: Aged; Aged, 80 and over; Anxiety; Depression; Fatigue; Female; Humans; Immunoglobulin Light-chain Amyloidosis; Male; Mental Health; Middle Aged; Natriuretic Peptide, Brain; Patient Reported Outcome Measures; Peptide Fragments; Prognosis; Prospective Studies

Topics: Biomarkers; Clinical Trials as Topic; Humans; Immunoglobulin Light-chain Amyloidosis; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Retrospective Studies; Survival Rate; Troponin T

Lenalidomide and dexamethasone (RD) is a standard treatment in relapsed/refractory immunoglobulin light chain (AL) amyloidosis (RRAL). We retrospectively investigated toxicity, efficacy and prognostic markers in 260 patients with RRAL. Patients received a median of two prior treatment lines (68% had been bortezomib-refractory; 33% had received high-dose melphalan). The median treatment duration was four cycles. The 3-month haematological response rate was 31% [very good haematological response (VGHR) in 18%]. The median follow-up was 56·5 months and the median overall survival (OS) and haematological event-free survival (haemEFS) were 32 and 9 months. The 2-year dialysis rate was 15%. VGHR resulted in better OS (62 vs. 26 months, P < 0·001). Cardiac progression predicted worse survival (22 vs. 40 months, P = 0·027), although N-terminal prohormone of brain natriuretic peptide (NT-proBNP) increase was frequently observed. Multivariable analysis identified these prognostic factors: NT-proBNP for OS [hazard ratio (HR) 1·71; P < 0·001]; gain 1q21 for haemEFS (HR 1·68, P = 0·014), with a trend for OS (HR 1·47, P = 0·084); difference between involved and uninvolved free light chains (dFLC) and light chain isotype for OS (HR 2·22, P < 0·001; HR 1·62, P = 0·016) and haemEFS (HR 1·88, P < 0·001; HR 1·59, P = 0·008). Estimated glomerular filtration rate (HR 0·71, P = 0·004) and 24-h proteinuria (HR 1·10, P = 0·004) were prognostic for renal survival. In conclusion, clonal and organ biomarkers at baseline identify patients with favourable outcome, while VGHR and cardiac progression define prognosis during RD treatment.

Topics: Adult; Aged; Antineoplastic Agents, Hormonal; Biomarkers; Cohort Studies; Dexamethasone; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Immunoglobulin Light Chains; Immunoglobulin Light-chain Amyloidosis; Immunologic Factors; Lenalidomide; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Progression-Free Survival; Recurrence; Retrospective Studies

Topics: Amyloidosis; Biomarkers; Humans; Immunoglobulin Light-chain Amyloidosis; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Troponin C

Topics: Aged; Atrial Fibrillation; Bilirubin; Bortezomib; Echocardiography; Electrocardiography; Female; Heart Failure; Humans; Immunoglobulin Light-chain Amyloidosis; Japan; Kaplan-Meier Estimate; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Regression Analysis; Retrospective Studies; Stroke Volume; Ventricular Dysfunction, Right; Ventricular Function, Left

Light chain (AL) cardiac amyloidosis is associated with a poor prognosis. Diagnosing at an early stage is critical for treatment and the management of cardiac complication.. We aimed to evaluate the diagnostic performance of

Topics: Adult; Aged; Aprotinin; Biopsy; Cardiomyopathies; Defibrillators, Implantable; Female; Humans; Immunoglobulin Light-chain Amyloidosis; Male; Middle Aged; Myocardium; Natriuretic Peptide, Brain; Organotechnetium Compounds; Peptide Fragments; Prospective Studies; Single Photon Emission Computed Tomography Computed Tomography

Immunoglobulin light-chain amyloidosis (AL) is a disease with limited treatment options due to the frailty of patients caused by organ damage. Since the clonal plasma cells often contain the cytogenetic aberration t(11;14), the Bcl-2 inhibitor venetoclax is suggested to have a role in the treatment of AL. Here, we report of a heart-transplanted patient, refractory to multiple therapies, reaching a rapid complete response with single-agent venetoclax.

Topics: Antineoplastic Agents; Bortezomib; Bridged Bicyclo Compounds, Heterocyclic; Dexamethasone; Female; Heart Transplantation; Humans; Immunoglobulin Light-chain Amyloidosis; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Proto-Oncogene Proteins c-bcl-2; Sulfonamides; Translocation, Genetic

The prognosis of cardiac light-chain (AL) amyloidosis is considered to be very poor. We studied the treatment efficacy and outcomes by retrospectively analyzing the clinical results of 45 patients with cardiac AL amyloidosis treated at our hospital between September 2008 and March 2016. The group of patients analyzed included 29 males and 16 females with a median age of 68 years. Their baseline median NT-proBNP, cTnT, and dFLC were 3167 pg/ml, 0.080 ng/ml, and 286.17 mg/l, respectively. Twenty-eight patients were in Cardiac Stage (CS) III and 17 patients were in Revised Prognostic Stage (RPS) IV. At the median follow-up of 10 months, the median overall survival (OS) was 16 months and 3-year OS was 35.9%. The patients in CS III showed significantly poorer survival rate than those in CS I or II (3-year OS: 12.2% vs. 65.8%, p = 0.0115) and the patients in RPS IV showed significantly poorer survival rate than those in RPS I, II, or III (3-year OS: 11.0% vs. 53.3%, p = 0.000914). Regardless of the therapeutic approaches, patients who achieved hematological CR or cardiac organ response demonstrated significantly improved prognosis. Therefore, achievement of hematological and organ responses is important in the treatment of cardiac AL amyloidosis.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Bortezomib; Cardiomyopathies; Cyclophosphamide; Dexamethasone; Drug Therapy, Combination; Female; Humans; Immunoglobulin Light-chain Amyloidosis; Japan; Male; Melphalan; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Peripheral Blood Stem Cell Transplantation; Prognosis; Retrospective Studies; Retroviridae Proteins, Oncogenic; Severity of Illness Index

Early diagnosis of cardiac involvement is a key issue in the management of AL amyloidosis. Our objective was to establish a diagnostic score of cardiac involvement in AL amyloidosis and to compare it with the current consensus criteria [i.e. left ventricular hypertrophy >12 mm and N-terminal pro b-type natriuretic peptide (NT-proBNP) >332 ng/L].. We carried out a prospective and multicenter study on AL amyloidosis patients who underwent cardiac evaluation including clinical examination, electrocardiography (ECG), cardiac biomarkers, transthoracic echocardiography (TTE), and cardiac magnetic resonance imaging (CMR). Cardiac involvement was based on CMR and/or endomyocardial biopsy. In a derivation cohort of 114 patients (82 with cardiac involvement), the highest diagnostic accuracy was observed with NT-proBNP and troponin blood levels, TTE-derived global longitudinal strain (LS), and apical to basal LS gradient. By using multivariate analysis, we established a diagnostic score including global LS ≥-17% (1 point), apical/(basal + median) LS ≥0.90 (1 point), and troponin T >35 ng/L (1 point). A score >1 was associated with sensitivity of 94% and specificity of 97%, an area under the curve of 0.98 [95% confidence interval (CI) 0.93-0.99] as well as a net reclassification index of 0.39 (95% CI 0.28-0.46) when compared with consensus criteria. In a validation cohort of 73 AL amyloidosis patients, the area under the receiver operating characteristic curve of the diagnostic score was 0.97 (95% CI 0.90-0.99).. Combining T troponin blood levels and two echo-derived strain parameters leads to very high accuracy for diagnosing cardiac involvement in AL amyloid patients.

Topics: Amyloidosis; Biomarkers; Cardiomyopathies; Echocardiography; Humans; Immunoglobulin Light-chain Amyloidosis; Natriuretic Peptide, Brain; Prognosis; Prospective Studies; Troponin T

Light Chain (AL) and transthyretin (ATTR) amyloidosis are the most common forms of amyloid cardiomyopathy. Population based studies describing the epidemiology and clinical features of amyloid cardiomyopathy are often based in tertiary medical centers and thus may be limited by referral bias.. We performed a cohort study of 198 patients diagnosed and treated in the Kaiser Permanente Northern California health care system who had a confirmed diagnosis of cardiac amyloidosis between 2001 and 2016. Associations between demographic, clinical, laboratory and imaging data and patient outcomes were quantified using multivariable Cox proportional hazard models for both the AL and ATTR groups. The average length of follow up was 2.8 years (SD 2.9 years) and overall survival was 69.1 percent at one year and 35.4 percent at five years. In the AL group, lower left ventricular ejection fraction (HR 1.33 per 5-point decrease, P < .001), coronary artery disease (HR 3.56, P < .001), and diabetes mellitus (HR 3.19, P < .001) were associated with all-cause mortality. Increasing age at the time of diagnosis with associated with higher all-cause mortality in both the AL and ATTR groups. Higher levels of B-type natriuretic peptide were associated with all-cause mortality in both groups: Top quartile BNP HR 6.17, P < .001 for AL and HR 8.16, P = .002 for ATTR.. This study describes a large cohort of patients with amyloid cardiomyopathy derived from a community based, integrated healthcare system and describes demographic, clinical, and laboratory characteristics associated with mortality and heart failure hospitalization. In this population, coronary artery disease, diabetes mellitus, and high BNP levels were strongly associated with mortality.

Topics: Age Factors; Aged; Aged, 80 and over; Amyloid Neuropathies, Familial; California; Cardiomyopathies; Cause of Death; Cohort Studies; Coronary Artery Disease; Delivery of Health Care, Integrated; Diabetes Mellitus; Echocardiography; Female; Heart Failure; Hospitalization; Humans; Immunoglobulin Light-chain Amyloidosis; Kaplan-Meier Estimate; Male; Middle Aged; Natriuretic Peptide, Brain; Proportional Hazards Models; Stroke Volume; Treatment Outcome

A useful biomarker for detecting cardiac amyloidosis (CA) has not been fully established. We aimed to investigate the utility of several biomarkers to detect CA in patients with amyloid light-chain (AL) amyloidosis.We examined the plasma levels of B-type natriuretic peptide (BNP), N-terminal fragment of the pro-brain natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T (hs-cTnT), serum amyloid A, and the difference between kappa and lambda free light chain (dFLC) between CA patients (n = 30, 47.6%) and non-CA patients (n = 33, 52.4%). Levels of BNP were significantly higher in the CA group compared to the non-CA group (1200.0 versus 224.0 pg/mL, P = 0.001). From the ROC analysis, the sensitivity and specificity of BNP for detecting CA (with a cut-off value of 412 pg/mL) were 83% and 70%, respectively, and the area under the receiver operating curve was 0.75 (95% CI 0.61-0.90, P < 0.001) in all AL amyloidosis patients (n = 63). In contrast, other markers such as NT-proBNP, hs-cTnT, serum amyloid A, and dFLC were not useful for detecting CA in AL amyloidosis patients. Additionally, in the Cox proportional hazard analysis, BNP was a predictor of all-cause mortality (hazard ratio 3.266, 95% confidence interval 1.498-7.119, P = 0.003).BNP is a useful biomarker for detecting cardiac involvement and predicting prognosis in AL amyloidosis patients.

Topics: Aged; Biomarkers; Cause of Death; Cohort Studies; Disease Progression; Echocardiography, Doppler; Electrocardiography; Female; Heart Diseases; Hospitals, University; Humans; Immunoglobulin Light-chain Amyloidosis; Japan; Kaplan-Meier Estimate; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Retrospective Studies; Risk Assessment; Survival Analysis; Troponin T

Topics: Aged; Biomarkers, Tumor; Female; Follow-Up Studies; Humans; Immunoglobulin Light-chain Amyloidosis; Male; Middle Aged; Natriuretic Peptide, Brain; Neoplasm Staging; Peptide Fragments; Retrospective Studies; Survival Rate; Troponin T

Topics: Biomarkers; Cardiomyopathies; Humans; Immunoglobulin Light Chains; Immunoglobulin Light-chain Amyloidosis; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Reproducibility of Results; Severity of Illness Index; Troponin T

Cardiac involvement occurs in more than half of the patients with light-chain amyloidosis (AL), but the characteristics, treatment and prognosis of cardiac AL (CAL) are not fully described. Methods and Results: A total of 227 patients with CAL diagnosis between January 2009 and March 2017 at Peking Union Medical College Hospital were included. Patients with Mayo stages I, II and III AL accounted for 0.9%, 49.8% and 49.3%, respectively. Autologous stem cell transplantation, bortezomib combinations, non-bortezomib regimens and palliative treatment were given as first line therapy in 3.1%, 44.1%, 30.8% and 22.0% of patients, respectively. Overall hematological response and cardiac response were achieved in 60.6% and 37.2% of evaluable patients, respectively. The median overall survival (OS) was 17 months in all patients, and 10 months in those with Mayo stage III. In patients with Mayo stage III disease who survived for >1 month, the bortezomib group survived significantly longer than the non-bortezomib group (median OS, not reached vs. 12 months, P=0.019). Three independent prognostic factors for survival were identified: N-terminal fragment of B-type natriuretic peptide (NT-proBNP) ≥5,000 pg/mL, bone marrow plasma cells ≥10%, and systolic blood pressure <100 mmHg.. CAL patients had poor prognosis, but those treated with bortezomib combinations had a better outcome than the non-bortezomib group.

Topics: Adult; Aged; Antineoplastic Agents; Blood Pressure; Bone Marrow Cells; Bortezomib; Cohort Studies; Female; Heart Diseases; Hematopoietic Stem Cell Transplantation; Humans; Immunoglobulin Light-chain Amyloidosis; Male; Middle Aged; Natriuretic Peptide, Brain; Palliative Care; Prognosis; Survival Analysis; Transplantation, Autologous; Treatment Outcome

Late gadolinium enhancement (LGE) pattern is a powerful imaging biomarker for prognosis of cardiac amyloidosis. It is unknown if the query amyloid late enhancement (QALE) score in light-chain (AL) amyloidosis could provide increased prognostic value compared with LGE pattern.Methods and Results:Seventy-eight consecutive patients with AL amyloidosis underwent contrast-enhanced cardiovascular magnetic resonance imaging. Patients with cardiac involvement were grouped by LGE pattern and analyzed using QALE score. Receiver operating characteristic curve was used to identify the optimal cut-off for QALE score in predicting all-cause mortality. Survival of these patients was analyzed with the Kaplan-Meier method and multivariate Cox regression. During a median follow-up of 34 months, 53 of 78 patients died. The optimal cut-off for QALE score to predict mortality at 12-month follow-up was 9.0. On multivariate Cox analysis, QALE score ≥9 (HR, 5.997; 95% CI: 2.665-13.497; P<0.001) and log N-terminal pro-brain natriuretic peptide (HR, 1.525; 95% CI: 1.112-2.092; P=0.009) were the only 2 independent predictors of all-cause mortality. On Kaplan-Meier analysis, patients with subendocardial LGE can be further risk stratified using QALE score ≥9.. The QALE scoring system provides powerful independent prognostic value in AL cardiac amyloidosis. QALE score ≥9 has added value to differentiate prognosis in AL amyloidosis patients with a subendocardial LGE pattern.

Topics: Aged; Female; Gadolinium; Humans; Immunoglobulin Light-chain Amyloidosis; Kaplan-Meier Estimate; Magnetic Resonance Imaging; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Risk Assessment; ROC Curve; Survival Analysis

Topics: Adult; Aged; Aged, 80 and over; Cardiomyopathy, Restrictive; Female; Humans; Immunoglobulin Light-chain Amyloidosis; Intention to Treat Analysis; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Survival Analysis

Topics: Amyloid; Antineoplastic Agents; Bortezomib; Cardiomyopathies; Cyclophosphamide; Dexamethasone; Fatigue; Hepatomegaly; Humans; Image-Guided Biopsy; Immunoglobulin Light-chain Amyloidosis; Immunohistochemistry; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Peritoneal Neoplasms; Splenomegaly; Tomography, X-Ray Computed; Treatment Outcome; Weight Loss

Chemotherapy combining cyclophosphamide, bortezomib and dexamethasone is widely used in light-chain amyloidosis. The benefit is limited in patients with cardiac amyloidosis mainly because of adverse cardiac events. Retrospective analysis of our cohort showed that 39 patients died with 42% during the first month. A new escalation-sequential regimen was set to improve the outcomes. Nine newly-diagnosed patients were prospectively treated with close monitoring of serum N-terminal pro-brain natriuretic peptide, troponin-T and free light chains. The results show that corticoids may destabilise the heart through fluid retention. Thus, a sequential protocol may be a promising approach to treat these patients.

Topics: Aged; Aged, 80 and over; Amyloidosis; Antineoplastic Combined Chemotherapy Protocols; Arrhythmias, Cardiac; Bortezomib; Cyclophosphamide; Death, Sudden, Cardiac; Dexamethasone; Female; Heart Diseases; Humans; Immunoglobulin kappa-Chains; Immunoglobulin lambda-Chains; Immunoglobulin Light Chains; Immunoglobulin Light-chain Amyloidosis; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Retrospective Studies; Troponin T; Water-Electrolyte Imbalance

Light chain amyloidosis (AL) results in tissue deposition of misfolded proteins, causing organ dysfunction. In an era of modern therapies, such as bortezomib, reassessment of the benefit of autologous hematopoietic cell transplantation (AHCT) should be considered. In this study, we compared outcomes between patients with AL receiving chemotherapy alone (CT) and those undergoing AHCT. Seventy-four patients with AL were analyzed retrospectively. Two cohorts of patients were studied, those receiving CT (n = 31) and those undergoing AHCT (n = 43). Of the 43 patients in the AHCT cohort, 29 received induction chemotherapy before AHCT, whereas 14 proceeded straight to AHCT without induction therapy. Compared with the CT cohort, patients in the AHCT cohort were younger and had higher ejection fractions, lower brain natriuretic peptide levels, and more severe proteinuria. The majority (87%) of patients in the CT cohort received bortezomib-based treatment. Transplantation-related mortality (TRM) was 7%. Patients receiving AHCT were more likely to achieve complete or very good partial response (P = .048). The median progression-free survival (PFS) and overall survival (OS) were superior in the AHCT cohort (not reached versus 9 months; P < .01 and 74 months versus 8 months; P = .03, respectively). Multivariable analysis demonstrated that improved PFS (hazard ratio, 3.86; 95% confidence interval [CI] 1.3 to 11.5; P = .02) and OS (hazard ratio, 5.6; 95% CI, 1.9 to 16; P < .001) were associated with use of AHCT compared with CT. Patients in the AHCT cohort had deeper and longer durations of response, with superior PFS and OS, compared with those in the CT cohort. Despite the limitations of this study, AHCT should be considered for eligible patients with AL at experienced transplantation centers that can offer this therapy with a low risk of TRM.

Topics: Adult; Aged; Antineoplastic Agents; Bortezomib; Female; Hematopoietic Stem Cell Transplantation; Humans; Immunoglobulin Light-chain Amyloidosis; Induction Chemotherapy; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Proportional Hazards Models; Proteinuria; Retrospective Studies; Stroke Volume; Transplantation, Autologous; Treatment Outcome

INTRODUCTION    Light‑chain (AL) amyloidosis is the most common cardiac amyloidosis. Despite progress in treatment, early mortality remains a substantial problem in these patients. OBJECTIVES    The aim of this study was to determine a clinical profile of patients diagnosed with AL amyloidosis in a cardiology department, as well as to define the cut‑off point for early mortality and identify predictors of early mortality in this population. PATIENTS AND METHODS    The study included 30 patients (14 women; median age, 61.5 years) with AL amyloidosis confirmed by echocardiography and biopsy of 2 organs. RESULTS    Six patients were diagnosed with stage II amyloidosis according to the Mayo 2004 classification, and 24 patients-with stage III. Early mortality was defined as death during 102 days after diagnosis and was observed in 14 patients. Patients who died earlier were younger and more frequently reported a weight loss of more than 10 kg and orthostatic hypotension than patients who died later. Moreover, they had higher concentrations of high‑sensitivity troponin T and N‑terminal pro‑B‑type natriuretic peptide (NT‑proBNP) and worse left and right ventricular (RV) contractility. In the Cox models, the age of less than 64 years, NT‑proBNP levels exceeding 4968 pg/ml, RV end‑diastolic diameter of less than 34 mm, and tricuspid annular plane systolic excursion lower than 13 mm were significant predictors of mortality within 102 days after diagnosis. CONCLUSIONS    We presented the results of the first Polish prospective noninterventional study on AL amyloidosis diagnosed in the cardiology department. We found that patients have advanced disease at the time of diagnosis. Younger age, impaired RV function, and higher concentrations of cardiac markers are predictors of worse prognosis.

Topics: Aged; Biomarkers; Cardiomyopathies; Female; Humans; Immunoglobulin Light-chain Amyloidosis; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Proportional Hazards Models; Prospective Studies; Troponin T; Ventricular Dysfunction, Right

Systemic light chain amyloidosis (AL amyloidosis) is the most common type of amyloidosis, in which deposition of misfolded monoclonal light chain secreted by underlying clonal plasma cells leads to organ dysfunction. Tissue biopsy of involved organ is needed to confirm the type of amyloid deposits, thus proper treatment could be applied. Laser microdissection followed by mass spectrometry, performed on formalin-fixed paraffin-embedded specimens, has been proven superior to traditional methods on accurate diagnosis of amyloidosis. Prognosis depends on the extent of cardiac involvement. The Mayo staging system using NT-ProBNP, cardiac troponin-T and free light chain, is the most robust method for risk stratification and treatment guidance. The introduction of autologous stem cell transplantation (auto-ASCT) resulted in long-term survival in responders, while treatment-related toxicity substantially limited the number of eligible candidates. Novel agents, especially bortezomib, thalidomide and lenalidomide hold promise to achieve comparable hematological responses with auto-ASCT, which might play significant role in treatment of recurrent or refractory AL amyloidosis.

Topics: Amyloidosis; Bortezomib; Hematopoietic Stem Cell Transplantation; Humans; Immunoglobulin Light Chains; Immunoglobulin Light-chain Amyloidosis; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis

In AL amyloidosis, the importance of right ventricle (RV) involvement has recently been underlined and its role in predicting prognosis has been emphasized. Little is known about the relationship between RV involvement, N-terminal pro-brain natriuretic peptide (NT-proBNP) and troponin levels. Aim of our study was to clarify the relationship between NT-proBNP and troponin and RV involvement and analyze their independent value as predictors of RV dysfunction.. We examined 76 consecutive patients with biopsy-proven AL amyloidosis. Each patient received complete clinical evaluation, troponin I, NT-proBNP assay and comprehensive echocardiographic evaluation. Considering a tricuspidal annulus plane systolic excursion (TAPSE) value <16 mm, 23 patients (30%) presented RV systolic dysfunction, whereas 53 (70%) did not. Patient with reduced TAPSE had thicker left ventricle (LV) walls and RV free walls, reduced LV fractional shortening, impaired LV diastolic function and worse LV and RV myocardial performance index. For RV dysfunction the best predictive value for NT-proBNP was identified as 2977 ng/l with sensitivity and specificity of 87% and 84%, respectively; best cut-off for troponin I was identified as 0.085 ng/l, with sensitivity and specificity of 85% and 90% respectively. At multivariable logistic regression analysis, both NT-proBNP and troponin I emerged as independent predictors of RV dysfunction presence but troponin appears to have a higher predictive power.. Our study demonstrated that cut-off values of 2977 ng/ml for NT-proBNP and 0.085 ng/l for troponin were able to identify a subgroup of AL patients with RV dysfunction. Troponin I is more accurate and seems to be the best biohumoral marker of RV dysfunction.

Topics: Aged; Amyloidosis; Biomarkers; Echocardiography; Female; Humans; Immunoglobulin Light-chain Amyloidosis; Logistic Models; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Troponin I; Ventricular Dysfunction, Right

Troponin-T (cTnT) and NT-proBNP provide prognostic information in light-chain amyloidosis (AL). Thus, these biomarkers are widely used in clinical routine for risk stratification. Recently, plasma level of osteopontin (OPN), a secreted phosphoglycoprotein expressed by a variety of cell types, has been reported as a risk predictor in various cardiovascular diseases.. OPN was determined retrospectively in 150 consecutive patients newly diagnosed with AL amyloidosis. All patients were evaluated according to a routine protocol including electrocardiography, echocardiography and laboratory testing.. Mean OPN was 591 ± 37 ng/mL. Cardiac involvement was established in 83 (55.3%). Median OPN plasma level were associated with number of organs involved, renal function, eligibility for high-dose melphalan chemotherapy and autologous stem cell transplantation, and severity of cardiac amyloidosis. Median follow-up was 19.2 months. 1-year all-cause-survival was 83.4%. The cut-offs discriminating 1-year all-cause-mortality for NT-proBNP, troponin T, and OPN were 2544 ng/L, 0.035 µg/L, and 426.8 ng/mL, respectively. Outcome was worse in patients with biomarkers above the individual ROC derived cut-off. A significant improvement of survival was observed in patients with cTNT >0.035 µg/L or NT-proBNP >2544 ng/L and OPN below ROC-derived cut-off of 426.8 ng/mL as compared to patients with OPN above 426.8 ng/L. No further discrimination was achieved by OPN in the cohorts of low troponin T or low NT-proBNP, respectively. Separate multivariate models identified OPN (cut-off 426.8 ng/mL) and troponin T (cut-off 0.035 µg/L) as independent predictors of all-cause-mortality.. These data demonstrated that OPN appears to be a valuable marker in the clinical routine for evaluation of patients with AL amyloidosis, especially if it is used in combination with cTNT and/or NT-proBNP.

Topics: Aged; Amyloidosis; Antineoplastic Agents, Alkylating; Biomarkers; Cardiomyopathies; Female; Gene Expression; Humans; Immunoglobulin Light Chains; Immunoglobulin Light-chain Amyloidosis; Male; Melphalan; Middle Aged; Natriuretic Peptide, Brain; Osteopontin; Peptide Fragments; Prognosis; Retrospective Studies; ROC Curve; Stem Cell Transplantation; Survival Analysis; Transplantation, Autologous; Troponin T

High-dose melphalan with autologous stem cell transplantation (HDM/ASCT) is a promising treatment option for eligible patients with systemic immunoglobulin light chain (AL) amyloidosis. We present the results of ASCT following risk-adapted melphalan conditioning on the basis of criteria proposed by our group, including B-type natriuretic peptide (BNP). Ten patients with primary systemic AL amyloidosis treated at our institute were evaluated. A full dose of melphalan (200 mg/m(2)) was administered to patients who met all the following: performance status, 0 or 1; number of organs involved, 2 or less; serum creatinine, 1.5 mg/dL or less; EF 50 % or more and BNP 200 pg/mL or less; otherwise 140 mg/m(2). The hematologic complete response was achieved in four and organ response was seen in two patients. The median event-free survival (EFS) of all patients was 21.5 months, and median overall survival (OS) was 47.0 months. EFS and OS were significantly longer for patients who received 200 mg/m(2) of melphalan than for those who received lower dose (EFS: not reached vs. 13.9 months, P = 0.0217; OS: not reached vs. 13.8 months, P = 0.0186). No treatment-related mortality within 100 days from ASCT was observed. Evaluation of cardiac diastolic function may contribute to safer HDM/ASCT and improve outcome of AL amyloidosis.

Topics: Adult; Amyloidosis; Female; Hematopoietic Stem Cell Transplantation; Humans; Immunoglobulin Light Chains; Immunoglobulin Light-chain Amyloidosis; Male; Melphalan; Middle Aged; Natriuretic Peptide, Brain; Retrospective Studies; Transplantation Conditioning; Transplantation, Autologous; Treatment Outcome

Treatment outcomes of patients with cardiac stage III light chain (AL) amyloidosis remain poorly studied. Such cases have been excluded from most clinical studies due to perceived dismal prognosis. We report treatment outcomes of 346 patients with stage III AL amyloidosis from the United Kingdom, Italy, Germany, and Greece. Median overall survival (OS) was 7 months with OS at 3, 6, 12, and 24 months of 73%, 55%, 46%, and 29%, respectively; 42% died before first response evaluation. On an intention-to-treat basis, the overall hematologic response rate was 33%, including a complete response rate of 12%. OS rates at 12 and 24 months, respectively, for 201 response evaluable patients were 88% and 85% for complete responders, 74% and 53% for partial responders, and 39% and 22% for nonresponders. Forty-five percent of responders achieved an organ response. Amino-terminal fragment of brain-type natriuretic peptide (NT-proBNP) >8500 ng/L and systolic blood pressure (SBP) <100 mm Hg were the only factors that independently impacted OS and identified an especially poor prognosis subgroup of patients with a median OS of only 3 months. Outcome and organ function of stage III AL amyloidosis without very elevated NT-proBNP and low SBP is improved by a very good hematologic response to chemotherapy.

Topics: Adult; Aged; Aged, 80 and over; Amyloidosis; Antineoplastic Combined Chemotherapy Protocols; Biomarkers; Europe; Female; Humans; Immunoglobulin Light-chain Amyloidosis; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Retrospective Studies; Survival Rate; Troponin T

In this issue of Blood, Wechalekar and colleagues demonstrate the importance of treating all patients with amyloidosis, no matter how severe their situation is, because clinically important responses are seen. They also identify the adverse prognostic impact of a systolic blood pressure of < 100 mm Hg.

Topics: Amyloidosis; Antineoplastic Combined Chemotherapy Protocols; Biomarkers; Female; Humans; Immunoglobulin Light-chain Amyloidosis; Male; Natriuretic Peptide, Brain; Peptide Fragments; Troponin T

Cardiac involvement is a dominant prognostic factor in AL amyloidosis patients. A detailed assessment of the presence and degree of cardiac involvement utilizes an array of noninvasive investigation methods, particularly echocardiography and MRI; laboratory parameters include troponins and natriuretic peptides. Cardiac involvement detection aside, cardiac bio-markers are used as a relatively strong stratification and prognostic factor.. The presentation of cardiac bio-markers assay applications in AL amyloidosis patients at an individual treatment center.. The monitored patient set consisted of 22 patients with histologically confirmed AL amyloidosis, of whom 18 met the criteria for cardiac involvement. Levels of cardiac bio-markers troponin T (TnT) and Nterminal probrain natriuretic peptide (NT ProBNP) were determined in all patients. Risk stratification of the patients utilized the Mayo staging system which is based on both bio-markers assays; Log Rank Test was applied to survival evaluation.. Median survival of patients with cardiac involvement stigmata was 10 months vs 60 months survival of patients without signs of cardiac involvement (p = 0.133). Of the 4 patients without cardiac involvement, 1 has shown positive levels of TnT and 2 positive levels of NT ProBNP. All cardiac involvement patients exhibited abnormal levels of NT ProBNP (median 4,752 ng/ l; 415.7- 35,000) as well as positive levels of TnT (median 0.0815 μg/ l; 0.02- 0.986). The application of the Mayo stratification system to the set had determined 2 patients at stage I, 5 patients at stage II and 15 patients at stage III. The median survival of the Mayo I + II group vs the Mayo III group was 60 vs 6 months (p = 0.015), revealing extremely limited survival of stage III patients. Assessment of TnT and NT ProBNP levels relative to treatment response shows that the degree of decrease in both markers depends on maximum treatment response -  respectively the attainment of a complete hematological remission.. The results, although obtained from a limited set of patients, confirm a definitive benefit of the application of cardiac bio-markers assay in the diagnostic and therapeutic algorithm of AL amyloidosis patients. The Mayo stratification system utilizing the cardiac indicator values represents a robust tool for risk stratification of AL amyloidosis patients.

Topics: Adult; Aged; Amyloid; Amyloidosis; Biomarkers; Cardiomyopathies; Echocardiography; Female; Humans; Immunoglobulin Light-chain Amyloidosis; Male; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Troponin T

To examine whether the outcome of patients with primary systemic amyloidosis (AL) has improved over time and to identify predictors of early mortality in patients with AL.. We studied 2 separate cohorts of patients. The first cohort, consisting of 1998 patients with AL seen at Mayo Clinic between January 1977 and August 2006, was used to examine the trends in overall survival (OS) from diagnosis during this 30-year period. The second cohort, consisting of 313 patients seen between September 2006 and August 2009, was used to validate a model for predicting early mortality.. The 4-year OS from diagnosis improved during each decade of follow-up: 21%, 24%, and 33%, respectively, for the periods 1977-1986, 1987-1996, and 1997-2006 (P<.001). Within the last group (1997-2006), 4-year OS during 1997-1999, 2000-2002, and 2003-2006 was 28%, 30%, and 42%, respectively (P=.02). However, the 1-year mortality remained high during the 30-year period. A risk stratification score using cardiac troponin T, N-terminal probrain natriuretic peptide, and uric acid identified patients at risk of early mortality. The 1-year mortality with 0, 1, 2, or 3 risk factors was 19%, 37%, 61%, and 80%, respectively, in this training cohort of 459 patients. This was confirmed in a validation cohort of 313 patients.. Survival in AL has improved over time, with maximum improvement occurring in the past decade. However, early mortality remains high, and prospective identification of patients at risk of early mortality may allow development of risk-adapted strategies.

Topics: Amyloidosis; Biomarkers; Female; Follow-Up Studies; Humans; Immunoglobulin Light-chain Amyloidosis; Logistic Models; Male; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prospective Studies; Risk Assessment; Risk Factors; Survival Analysis; Troponin T; Uric Acid