N-terminal Pro Natriuretic Peptide Research Articles

The involvement of kidneys in chronic heart failure patients with liver steatosis

Recently, the internist-practitioner does not routinely assess glomerular filtration rate (GFR) in there no risk factors for chronic kidney disease (CKD). However, recent data shows that in non-alcoholic fatty liver disease (NAFLD) it is necessary to assess GFR even without any classic risk factors for CKD. Early awareness of kidney damage in chronic heart failure patients (CHF) and NAFLD might help to select those requiring further investigation and treatment, taking into account comorbidity. Aim. To assess functional condition of kidneys in CHF patients with liver steatosis. Material and methods. Totally, 77 CHF patients included. All patients had confirmed CHF diagnosis by N-terminal Brain pro-natriuretic peptide assay. The severity of clinical condition in CHF was assessed, functional status of patient. All patients underwent clinical and biochemical blood sampling, electrocardiography, ultrasound liver imaging. The heart chambers sizes were assessed, walls thickness by echocardiography. All patients had the GFR by CKD-EPI calculated, as the Fatty Liver Index (FLI), NAFLD Fibrosis Score (NFS). Results. More than a half (66%) of patients with CHF had C2 stage of CKD, 6% — С1, 12% — С3а, 9% — С3б, 4% — С4 stage of CKD. Patients with С5 were absent. Mean GFR was 65,4±14,4 ml/min/1,73 m2. In statistical analysis it was revealed that while there is an increase of SCAHF points, there is parallel increase of CKD stage (p=0,0027). Higher glucose level, higher the stage of CKD (p=0,0022). It was found, that while there is and increase of CKD, right atrium size also increases (p=0,044). With more severe renal damage in CHF, higher the level of PIIINP myocardium fibrosis marker (p=0,047). According to FLI, in 40% of patients there is high chance for liver steatosis, in 34% of patients the data on steatosis was absent, in 26% was intermediate. According to NFS, 26% patients had high probability of liver fibrosis, 9% — did not have, 65% were in a “grey zone”. In analysis of relations there was found that while increasing NFS, GFR does decrease, and CKD stage increases (p=0,049). Conclusion. Patients with NAFLD and CHF do need GFR assessment. Early finding of renal involvement in CHF with NAFLD would help to select patients for further investigation and therapy prescription, taking into account comorbidity.

Cross-laboratory analytical validation of the cardiac biomarker NT-proANP in rat

IntroductionNatriuretic peptides, including N-terminal-proatrial natriuretic peptide (NT-proANP) are cardiac hormones that are produced in response to myocardial stretch and have been used in rats and humans as blood based functional cardiac biomarkers. There are limited validation data of these assays in rats and therefore the Predictive Safety Testing Consortium, Cardiac Hypertrophy Working Group (PSTC—CHWG) performed a cross-laboratory (5 laboratories) analytical evaluation of a commercially available NT-proANP ELISA for use with rat samples. MethodsSerum samples were collected from normal Sprague Dawley (SD) rats and were spiked with kit calibrator material or rat heart tissue extracts to provide specimens for the validation. In addition, the cardiotoxicant, isoproterenol, was used to induce elevated endogenous NT-proANP levels in a subgroup of rats for additional validation specimens. The Biomedica™ (BI-20892, Vienna, Austria) proANP (1-98) enzyme-linked immunoabsorbent assay (ELISA) kit was used to measure NT-proANP. Intra-assay and inter-assay precisions, accuracy, sample linearity, recovery, limit of detection, upper and lower limits of quantitation (ULOQ and LLOQ, respectively), sample-freeze/thaw stability and stored sample stability were assessed and compared to pre-determined acceptance criteria. ResultsThe majority of the experimental assessments met the established validation criteria, however there were individual results that did not meet these standards. Overall, acceptable intra- and inter-assay precisions and accuracies as well as inter-laboratory precision and accuracy were demonstrated. Linearity and recovery values fell within the pre-determined acceptance criteria, samples remained stable for up to three freeze–thaw cycles and frozen samples were stable at ~−70°C for 12months. The limit of detection (LOD) and LLOQ and ULOQ were similar to those specified by the manufacturer. DiscussionOverall, the assay was demonstrated to be technically adequate for the detection of NT-proANP serum levels in SD rats.

N-terminal natriuretic propeptide in diagnostics of myocardial injuries after coronary artery bypass grafting on a beating heart

Dynamics of N-terminal natriuretic propeptide (NT-proBNP) and troponin T in the blood of patients with ischemic heart disease after CABG on a beating heart is studied. It is found out that the level of NT-proBNP in patients with ischemic heart disease at admission correlates with their functional class, left ventricular ejection fraction and end-diastolic volume). It is also shown that the level of NT-proBNP increases in 1 day after CABG and reaches the maximum values in3 days. At the 15th day a decrease in the level of NT-proBNP is observed, however, which reaches the baseline values. The analysis of correlation between NT-proBNP and troponin Т has revealed an inverse correlation between the indicators under study, which testifies to the fact that NT-proBNP cannot be used as a myocardial injury marker in patients with ischemic heart disease after CABG.

Circulating Atrial Natriuretic Peptide Genetic Association Study Identifies a Novel Gene Cluster Associated with Reduced NT-proANP, Increased Stroke and Higher Diastolic Blood Pressure

The goal of this study was to identify genetic determinants of plasma N-terminal proatrial natriuretic peptide (NT-proANP) in the general community by performing a large-scale genetic association study and to assess its functional significance in in vitro cell studies and on disease susceptibility.

Plasma concentration of N-terminal pro-atrial and N-terminal pro-brain natriuretic peptides and fluid balance in children with bronchiolitis.

The aim of this study was to evaluate the plasma levels of N-Terminal pro-brain natriuretic peptide (N-BNP), N-Terminal pro-atrial natriuretic peptide (N-ANP) and antidiuretic hormone (ADH) over time and their relationship to clinical indicators in hospitalized children with bronchiolitis. Prospective crossover clinical investigation. Hospitalized children in a university-affiliated hospital. Twenty-seven children (birth to 24 mo) with first episode of bronchiolitis and 34 age-matched healthy controls. Daily blood samples up to five consecutive days were obtained for N-BNP, N-ANP and ADH in the bronchiolitis group and on the initial blood draw in the control group. Daily total fluid intake, net fluid balance and clinical bronchiolitis severity levels were recorded. N-BNP and N-ANP levels were measured by enzyme-linked immunosorbent assay. ADH levels were measured by a double antibody technique. The mean age (months ± SD) in the bronchiolitis group was 4.2 ± 5.9 mo and 12.0 ± 6.1 mo in the control group; 51.9% of bronchiolitis patients were positive for respiratory syncytial virus (RSV). In patients with bronchiolitis on admission, plasma N-BNP measurements (mean ± SD) were elevated (996.0 ± 570.2 fmol/mL) compared to controls (552.7 ± 264.7 fmol/mL P < 0.005). Serum N-ANP levels were also initially elevated (3,889 ± 1,769.7 fmol/mL) compared to controls (2,173 ± 912 fmol/mL P < 0.005). The serum levels of N-BNP and N-ANP remained significantly elevated from day 2 through day 5. Similarly, ADH levels were significantly higher on admission in the bronchiolitis group (10 ± 7.49 pg/mL) vs. the control group (5.8 ± 5.5 pg/mL P < 0.05), but quickly decreased from day 2 through day 5. N-BNP, N-ANP and ADH concentrations were elevated in hospitalized children with bronchiolitis at admission. Based on our observation, judicious fluid management is indicated in children hospitalized with bronchiolitis.

Integrated approach to early detection of cardiovascular toxicity induced by a ghrelin receptor agonist.

Cardiovascular (CV) safety concerns are among the leading causes of compound attrition in drug development. This work describes a strategy of applying novel end points to a 7-day rodent study to increase the opportunity to detect and characterize CV injury observed in a longer term (ie, 28 days) study. Using a ghrelin receptor agonist (GSK894281), a compound that produces myocardial degeneration/necrosis in rats after 28 days at doses of 0.3, 1, 10, or 60 mg/kg/d, we dosed rats across a range of similar doses (0, 0.3, 60, or 150 mg/kg/d) for 7 days to determine whether CV toxicity could be detected in a shorter study. End points included light and electron microscopies of the heart; heart weight; serum concentrations of fatty acid-binding protein 3 (FABP3), cardiac troponin I (cTnI), cardiac troponin T (cTnT), and N-terminal proatrial natriuretic peptide (NT-proANP); and a targeted transcriptional assessment of heart tissue. Histologic evaluation revealed a minimal increase in the incidence and/or severity of cardiac necrosis in animals administered 150 mg/kg/d. Ultrastructurally, mitochondrial membrane whorls and mitochondrial degeneration were observed in rats given 60 or 150 mg/kg/d. The FABP3 was elevated in rats given 150 mg/kg/d. Cardiac transcriptomics revealed evidence of mitochondrial dysfunction coincident with histologic lesions in the heart, and along with the ultrastructural results support a mechanism of mitochondrial injury. There were no changes in cTnI, cTnT, NT-proANP, or heart weight. In summary, enhancing a study design with novel end points provides a more integrated evaluation in short-term repeat dose studies, potentially leading to earlier nonclinical detection of structural CV toxicity.

A corin variant identified in hypertensive patients that alters cytoplasmic tail and reduces cell surface expression and activity.

Corin is a membrane-bound protease that regulates blood pressure by activating the natriuretic peptides. CORIN variants have been associated with hypertension and heart disease in African Americans. In this study, we conducted targeted exome sequencing and identified an insertion variant, c.102_103insA, in exon 1 of the CORIN gene. Analysis of two independent cohorts showed that the variant was preferentially present in hypertensive patients (38/795 or 4.78% vs. 4/632 or 0.63% in normal individuals, p = 4.14E-6). The insertion shifted the reading frame, resulting in a corin variant with a truncated cytoplasmic tail. In cell-based studies, the corin variant exhibited poor trafficking in the Golgi, reduced cell surface expression and zymogen activation, and low natriuretic peptide processing activity. Compared with normal individuals with the wild-type allele, individuals with the variant allele had lower levels of plasma corin [0.59 ± 0.07 ng/mL (n = 25) vs. 0.91 ± 0.02 ng/mL (n = 215), p<0.001] and higher levels of plasma N-terminal pro-atrial natriuretic peptide (NT-pro-ANP) [2.39 ± 3.6 nmol/L (n = 21) vs. 0.87 ± 0.6 nmol/L (n = 48), p = 0.005]. These results indicate that the variant altered corin structure and impaired the natriuretic peptide processing activity in vivo. The results highlight corin defects as an important underlying mechanism in hypertension.

Circulating atrial natriuretic peptide genetic association study identifies a novel gene cluster associated with stroke in whites.

The goal of this study was to identify genetic determinants of plasma N-terminal proatrial natriuretic peptide (NT-proANP) in the general community by performing a large-scale genetic association study and to assess its functional significance in in vitro cell studies and on disease susceptibility. Genotyping was performed across 16 000 genes in 893 randomly selected individuals, with replication in 891 subjects from the community. Plasma NT-proANP1-98 concentrations were determined using a radioimmunoassay. Thirty-three genome-wide significant single-nucleotide polymorphisms were identified in the MTHFR-CLCN6-NPPA-NPPB locus and were all replicated. To assess the significance, in vitro functional genomic studies and clinical outcomes for carriers of a single-nucleotide polymorphism rs5063 (V32M) located in NPPA that represented the most significant variation in this genetic locus were assessed. The rs5063 variant allozyme in transfected HEK293 cells was decreased to 55±8% of wild-type protein (P=0.01) as assessed by quantitative western blots. Carriers of rs5063 had lower NT-proANP levels (1427 versus 2291 pmol/L; P<0.001) and higher diastolic blood pressures (75 versus 73 mm Hg; P=0.009) and were at an increased risk of stroke when compared with wild-type subjects independent of age, sex, diabetes mellitus, hypertension, atrial fibrillation, and cholesterol levels (hazard ratio, 1.6; P=0.004). This is the first large-scale genetic association study of circulating NT-proANP levels performed with replication and functional assessment that identified genetic variants in the MTHFR-CLCN6-NPPA-NPPB cluster to be significantly associated with NT-proANP levels. The clinical significance of this variation is related to lower NT-proANP levels, higher blood pressures, and an increased risk of stroke in the general community.

Ideal cardiovascular health: associations with biomarkers and subclinical disease and impact on incidence of cardiovascular disease in the Framingham Offspring Study.

The American Heart Association Cardiovascular Health score (CVH score) is inversely associated with cardiovascular disease (CVD) incidence, but the mechanisms underlying this association warrant exploration. We related the CVH score to circulating biomarkers and prevalent subclinical CVD (defined as ≥1 of the following: increased carotid intima-media thickness or stenosis, left ventricular hypertrophy [by ECG or echocardiography], left ventricular systolic dysfunction, microalbuminuria, and a reduced ankle-brachial index) in 2680 Framingham Study participants (mean age, 58 years; 55% women). After adjustment for age and sex, an ideal CVH score (nonsmoking status, ideal body mass index, regular physical activity, healthy diet, and an optimal profile of serum cholesterol, blood pressure, and glucose; 1 point for each) was associated with higher circulating concentrations of natriuretic peptides (N-terminal pro-atrial natriuretic peptide and B-type natriuretic peptide) and lower blood concentrations of plasminogen activator inhibitor-1, aldosterone, C-reactive protein, D-dimer, fibrinogen, homocysteine, and growth differentiation factor-15 levels (P<0.001 for all), as well as lower odds of subclinical disease (odds ratio, 0.74 per 1-unit increase in CVH score; 95% confidence interval, 0.68-0.80). The incidence of CVD (267 events over 16 years) was inversely associated with the CVH score in age- and sex-adjusted models (hazard ratio, 0.77 per 1-unit increase in CVH score; 95% confidence interval, 0.70-0.86), which was slightly attenuated upon adjustment for biomarkers and subclinical disease (hazard ratio, 0.87; 95% confidence interval, 0.78-0.97). In our prospective community-based study, the inverse association between an ideal cardiovascular health score and CVD incidence was partly attributable to its favorable impact on CVD biomarker levels and subclinical disease.

Melphalan and dexamethasone with or without bortezomib in newly diagnosed AL amyloidosis: a matched case-control study on 174 patients.

Oral melphalan and dexamethasone (MDex) is a standard treatment for patients with AL amyloidosis who are not eligible for stem cell transplantation at many referral centers. However, following encouraging reports on the activity of bortezomib combined with alkylators and dexamethasone, these combinations are being moved to frontline therapy. We compared the outcome of 87 patients treated with bortezomib plus MDex (BMDex) with that of 87 controls treated with MDex. Patients and controls were matched for age, cardiac and renal function and free light chain burden. A higher rate of complete responses was observed with BMDex (42 vs 19%), but this did not result in a survival improvement in the overall population. However, a significant survival advantage for BMDex was observed in patients without severe (New York Heart Association class III or IV) heart failure and with N-terminal pro-natriuretic peptide type-B <8500 ng/l. Patients treated with full-dose dexamethasone had similar response rates and survival whether they received bortezomib or not. Intermediate-risk patients who are not fit enough to receive high-dose dexamethasone are likely to take the greatest advantage from the addition of bortezomib to MDex.

Increased NT-proANP predicts risk of congestive heart failure in Cavalier King Charles spaniels with mitral regurgitation caused by myxomatous valve disease

ObjectivesTo evaluate the predictive value of plasma N-terminal pro-atrial natriuretic peptide (NT-proANP) and nitric oxide end-products (NOx) as markers for progression of mitral regurgitation caused by myxomatous mitral valve disease. AnimalsSeventy-eight privately owned Cavalier King Charles spaniels with naturally occurring myxomatous mitral valve disease. MethodsProspective longitudinal study comprising 312 measurements over a 4.5 year period. Clinical values were recorded, NT-proANP concentrations were measured by radioimmunoassay, and NOx were analyzed colorimetrically. To predict congestive heart failure (CHF), Cox proportional hazards models with time-varying covariates were constructed. ResultsThe hazard ratio for NT-proANP (per 1000 pmol/l increase) to predict future CHF was 6.7 (95% confidence interval, 3.6–12.5; p < 0.001). The median time to CHF for dogs with NT-proANP levels >1000 pmol/l was 11 months (95% confidence interval, 5.6–12.6 months), compared to 54 months (46 – infinity) for dogs with concentrations ≤1000 pmol/l (p < 0.001). Due to intra- and inter-individual variability, most corresponding analyses for NOx were insignificant but dogs reaching CHF had a lower mean NOx concentration than dogs not reaching CHF (23 vs. 28 μmol/l, p = 0.016). Risk of CHF increased with increase in heart rate (>130 beats per minute) and grade of murmur (≥3/6). ConclusionsThe risk of CHF due to mitral regurgitation is increased in dogs with blood NT-proANP concentrations above 1000 pmol/l. Measurement of NT-proANP can be a valuable tool to identify dogs that may develop CHF within months.

0283: Correlation between N-terminal pro-natriuretic peptide levels and left atrial size in patients with left ventricular systolic dysfunction

Elevated N-terminal Pro B-type Natriuretic Peptide (NT Pro-BNP) levels are correlated with the severity of left ventricular systolic dysfunction and left ventricular filling alterations. Besides, left atrial (LA) size is believed to reflect chronic diastolic dysfunction. Evaluate the relationship between NT Pro-BNP and LA size. 81 patients (77.7% males; mean age, 61.55±15 years), with left ventricular systolic dysfunction (left ventricular ejection fraction [LVEF] <55%), underwent transthoracic echocardiography to evaluate LA size and venous blood sampling to determine NT-pro-BNP levels. Mean LVEF was 35.6±10.8 % (LVEF <35% in 32 patients). The NT Pro-BNP values were elevated (mean 3304±4218.9 pg/ml). Higher NT Pro-BNP was significantly correlated to LA size (r=0.56, p<0.001). The optimal cut-off value to predict LA size >20 cm2 was 1188 pg/mL (area under the receiver-operating characteristic curve [AUC] 0.83 [0.71–0.93], p<0.0001, sensitivity 77.6%, specificity 75%). The present study shows that plasma NT Pro-BNP levels is strongly correlated to LA size. NT-proBNP level more than 1188 pg/mL may suggest LA dilatation.

Ropinirole treatment in Parkinson's disease associated with higher serum level of inflammatory biomarker NT-proCNP

There is rapidly growing evidence for the influence of inflammation on the development and progression of Parkinson's disease (PD). N-terminal pro C-type Natriuretic Peptide (NT-proCNP) is a novel potential inflammatory biomarker and has been recently correlated in PD with pro- and anti-inflammatory cytokines, especially TNF-α and IL-10. The study aims to explore serum level of NT-proCNP in group consisted of 132 patients with idiopathic Parkinson's disease (age 59.6±15.l years) and 46 healthy controls (age 58.5±11.5 years). Serum level of NT-proCNP was significantly higher in PD patients than in the control group (p<0.05; PD vs control: mean 3.65±5.5 vs 1.49±0.73, median 1.81 vs 1.46). The serum level of NT-proCNP was directly correlated with the treatment with dopamine agonist (ropinirole) (R=0.38; p<0.05). The higher serum level of NT-proCNP in PD patients being treated with ropinirole suggests a potential proinflammatory characteristic of dopamine agonists.

An N-terminal pro-atrial natriuretic peptide (NT-proANP) ‘aggregation-prone’ segment involved in isolated atrial amyloidosis

Isolated atrial amyloidosis (IAA) is a common localized form of amyloid deposition within the atria of the aging heart. The main constituents of amyloid fibrils are atrial natriuretic peptide (ANP) and the N-terminal part of its precursor form (NT-proANP). An ‘aggregation-prone’ heptapeptide (114KLRALLT120) was located within the NT-proANP sequence. This peptide self-assembles into amyloid-like fibrils in vitro, as electron microscopy, X-ray fiber diffraction, ATR FT-IR spectroscopy and Congo red staining studies reveal. Consequently, remedies/drugs designed to inhibit the aggregation tendency of this ‘aggregation-prone’ segment of NT-proANP may assist in prevention/treatment of IAA, congestive heart failure (CHF) or atrial fibrillation (AF).

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Short‐Term Hemodynamic and Neuroendocrine Effects of Pimobendan and Benazapril in Dogs with Myxomatous Mitral Valve Disease and Congestive Heart Failure

Pimobendan and benazepril are frequently used with diuretics to treat dogs in congestive heart failure (CHF) caused by myxomatous mitral valve disease (MMVD). To compare the short-term effects of pimobendan versus benazepril on pump function, heart size, and neuroendocrine profile in dogs with CHF caused by MMVD. Sixteen client-owned dogs. Seven-day prospective single-blinded study of dogs stabilized on furosemide monotherapy, randomized to pimobendan (0.4-0.6 mg/kg/day) or benazepril (0.25-1.0 mg/kg/day). Dogs had first-pass radionuclide angiocardiography, and heart size was measured by radiography and echocardiography. Circulating neuroendocrine hormones were measured. Baseline variables did not differ between treatment groups. Greater decreases in the pimobendan than in the benazepril group were found for heart rate (P = .001), heart rate-normalized pulmonary transit time (P = .02), left atrial size (P = .03), and systolic and diastolic left ventricular diameters (P < .001 and P = .03, respectively) and volumes (P < .001 and P = .02, respectively), whereas ejection fraction increased more (P = .02) in the pimobendan group. Of the neuroendocrine hormones, only N-terminal proatrial natriuretic peptide (NT-ProANP) differed (P = .04) between groups. Within groups, plasma aldosterone increased (P = .01), and NT-proANP (P = .01) and NT-proB-type (P = .02) natriuretic peptide decreased in the pimobendan group, and NT-proANP (P = .02) and plasma vasopressin (P = .01) decreased in the benazepril group. Pimobendan improves short-term cardiac function more than benazepril in dogs with CHF caused by MMVD. Pimobendan treatment enables the heart to work at smaller end-systolic and diastolic dimensions while maintaining adequate forward stroke volume. Some of the treatment responses found in neuroendocrine profile might have therapeutic relevance.

GW24-e2957 Efficacy of ivabradine in combination with metoprolol versus uptitration of metoprolol in patients after Q-wave myocardial infarction with early left ventricular systolic dysfunction

ObjectivesThe purpose of the study was to evaluate the effect of combination of ivabradine with metoprolol tartrate versus uptitration of metoprolol tartrate on left ventricular (LV) systolic function and plasma...

FRI0453 Patients with ankylosing spondylitis have elevated soluble biomarkers of cardiovascular disease compared to controls

BackgroundPatients with ankylosing spondylitis (AS) have higher risk of atherosclerotic cardiovascular disease (CVD) than the general population, but few have studied soluble biomarkers of CVD in AS. Asymmetric dimethylarginine (ADMA)...

Long Term Heart Failure Management in Children with Dilated Cardiomyopathy

Purpose Carvedilol and biomarkers do not have established roles in pediatric HF. We reviewed our 14-year experience to assess the role of N-terminal pro Natriuretic peptide (NTproBNP) and use of carvedilol in children with dilated cardiomyopathy (DCM). Methods and Materials We reviewed dosage of medications, echocardiogram measurements of ejection fraction (EF), fractional shortening corrected by age (FSz), left ventricular end diastolic diameter corrected by BSA (LVEDDz) and NTproBNP to assess outcome and response to treatment. Results There were 106 children with DCM (58 male). Mean age at presentation was 7.4±6.5 years. Mean EF and FSz at presentation were 28.9±10 and −8.1±6.7. Carvedilol and ACE inhibitors were used in combination in 72% of patients. Digoxin was used in symptomatic patients. Average dose (mg/kg/day) of carvedilol was 0.95 (range 0.05-1.7), enalapril 0.64 (0.08-1.2) and captopril 3.4 (0.45-6.4). Average follow up was 6.2±5.5 years. Death/transplant (DT) occurred in 45% of children; 40% of those occurred within one year of presentation. In the survivors, EF and FSz improved from 29.3±9.6 to 53.8±9 (p Conclusions Mortality and transplant remain common outcomes for children with DCM, particularly in the first year following presentation. Carvedilol and ACE inhibitors are safely tolerated with long-term use, and at higher doses than previously reported. Hypoglycemia may be a serious side effect that can be avoided by taking carvedilol with food. Persistent NTproBNP≥1000 may indicate need for transplantation.

Treatment of AL Amyloidosis with Bendamustine

AbstractAbstract 4057Combinations of older drugs and novel agents are constantly improving the outcome of chemotherapy in AL amyloidosis. Bendamustine has demonstrated activity in multiple myeloma and Waldenström macroglobulinemia. In the present study we evaluated the safety and efficacy of Bendamustine and prednisone (BeP) in 36 patients with AL amyloidosis from two European referral centers, the Amyloidosis Center (Heidelberg, Germany) and the Amyloidosis Research and Treatment Center (Pavia, Italy).The databases of the two centers were systematically searched for patients with AL amyloidosis treated with BeP. Nineteen patients were treated in Heidelberg and 17 in Pavia. The patients received 28-day cycles of bendamustine (60–100 mg/m2 on days 1 and 2) and prednisone (100 mg on days 1–4). The target dose of bendamustine was 100 mg/m2, and lower doses were used in 20 patients (55%) who had baseline cytopenia. Ten patients (28%) had IgM clones. Of them, 8 received rituximab associated with BeP. Response was evaluated according to the novel criteria of the International Society of Amyloidosis. Patients’ characteristics are reported in Table 1. Severe (grade 3 or 4) adverse events (SAE) were observed in 33% of subjects, most common being cytopenia (17%). Other SAEs were fever (6%), portal vein thrombosis, skin rash, renal failure, and weight loss, in 1 patient each. By intention to treat, 17 patients (47%) achieved hematologic response, with complete remission (CR) in 1 case (3%), and very good partial response in 2 (6%). The median time to response was 3 months. The dose of bendamustine administered in each cycle was not associated with response. Three out of 5 treatment-naïve patients responded. Interestingly, amongst the 8 subjects with IgM clones receiving BeP combined with rituximab, 6 (75%) responded (1 CR), including 1 out of 3 subjects who were refractory to previous rituximab. Amongst 10 patients who were refractory to melphalan, bortezomib and lenalidomide, 4 responded to BeP. Cardiac responses were observed in 3 patients (12%), two of whom also had liver response and one improvement of peripheral neuropathy. Overall, 12 patients (33%) died, and 65% of patients are alive after 3 years. Two subjects died within 3 months from treatment initiation due to advanced cardiac amyloidosis. A troponin I concentration >0.1 ng/mL or a high-sensitivity troponin T level >77 ng/L negatively affected survival (median 5 vs. 45 months, P=0.003). In a 3-month landmark analysis, response to BeP conferred a significant survival advantage (Figure 1).Treatment with bendamustine is effective and well tolerated, representing an additional treatment option in AL amyloidosis, particularly as salvage therapy. Its use in combination with rituximab in IgM patients is very promising, and warrants further studies in prospective international trials.Table 1Patients' characteristicsVariableN (%)/median (range)Newly diagnosed5 (14)Refractory to previous therapy24 (67)Relapsed after previous therapy7 (19)Number of prior therapies2 (0–5)Previous treatment type:alkylating agents29 (81)bortezomib16 (44)lenalidomide12 (33)thalidomide6 (17)rituximab*6 (17)Male gender18 (50)Age, years66 (33–80)Organ involvementheart25 (69)kidney20 (56)soft tissues13 (36)liver10 (28)peripheral nervous system8 (22)Two or more organs involved22 (61)New York Heart association class III or IV14 (39)Cardiac Stage°I9 (28)II19 (59)III4 (13)Estimated glomerular filtration rate22 (61)≥60 mL/min per 1.73 m211 (31)30–59 mL/min per 1.73 m23 (8)<30 mL/min per 1.73 m2Bone marrow infiltration15 (3–30)*Used in patients with IgM clones.°Available in 32 patients. Cardiac staging was based on N-terminal pro-natriuretic peptide type-B (cutoff 332 ng/L) and cardiac troponin I (cutoff 0.1 ng/mL) or high-sensitivity troponin T (cutoff 77 ng/L). Stage I patients had both markers below the cutoffs, stage II only one marker above the cutoffs and stage III patients both markers above the cutoffs. [Display omitted] Disclosures:Off Label Use: Use of bendamustine in AL amyloidosis.