P2733Prognostic value of cardiac dysautonomia in AL amyloidosis

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M Nicol ◽  
A Cescau ◽  
M Baudet ◽  
S Harel ◽  
B Royer ◽  
...  
Keyword(s):  
Mayo Clinic ◽  
Cardiac Involvement ◽  
Nyha Class ◽  
Adverse Outcomes ◽  
Blood Levels ◽  
Al Amyloidosis ◽  
Class Iii ◽  
Cardiac Denervation ◽  
A Prospective Study

Abstract Introduction Cardiac involvement is the major prognostic factor in patients with light chain amyloidosis (AL). Cardiac dysautonomia can occur early in amyloidosis and can be assess by Iodine-123-metaiodobenzylguanidine (123I-MIBG) scintigraphy. Its prognostic value has been shown in TTR amyloidosis but is unknown in AL amyloidosis. We aimed to evaluate the prognosis impact of cardiac dysautonomia in patients with AL amyloidosis. Methods We carried out a prospective study in consecutive patients with biopsy-proven AL amyloidosis. All patients underwent clinical examination, EKG, echocardiography, cardiac MRI and biological tests. The 2012 Mayo clinic prognostic classification was calculated by using blood levels of NT-proBNP, cardiac T troponin and the differential of free light chains as recommended. The sympathetic cardiac innervation was assessed by using 123I-MIBGscintigraphy and measurement of the heart-to-mediastinum uptake ratio (late H/M) in the anterior view of the chest. A cardiac denervation was defined by late H/M <1.8 4h after injection of 3 MBq/kg of 123I-MIBG. The primary end-point was all-cause mortality during follow-up. Results Fifty consecutive patients with AL amyloidosis were included. The median age was 68 years old [58–73]. By using both echocardiography and MRI, cardiac involvement was diagnosed in 33 patients (66%) and thirteen of these patients were NYHA class III or IV. By using Mayo clinic classification, patients were I, II, III and IV classes in 9 (18%), 14 (28%), 16 (32%) and 11 (22%) cases respectively. According to echocardiographic data, the median wall thickness of left ventricle was 13 mm [12–15]. The late H/M was 1.51 [1.33–1.67]. Cardiac denervation was found in 44 patients (88%). The 6 patients (12%) with a normal late H/M had no cardiac amyloidosis involvement. During a median follow-up of 24 months, 9 patients (18%) died. The area under the ROC curve of late H/M for predicting death was 0.74 (CI 95% 0.58–0.86). According to this curve, the best threshold was 1.44 and 7 of the 9 patients who died had late H/M ≤1.44. The figure shows the 2 year-survival according to late H/M. Late H/M ≤1.44 predicted all-cause death irrespective of the Mayo clinic classification: HR 8.0 (CI 95% 2.1–63) after adjustment on the Mayo clinic score (p=0.005). In addition, unplanned hospitalization for heart failure occurred in 8 patients with late H/M ≤1.44 versus 3 patients with late H/M >1.44 (p=0.03). Survival according to late H/M Conclusion Late H/M ≤1.44 is predictive of adverse outcomes in patients with AL amyloidosis, independently of the Mayo Clinic prognostic classification.

Benefits of tafamidis in patients with advanced transthyretin amyloid cardiomyopathy

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
C Rapezzi ◽  
A.V Kristen ◽  
B Gundapaneni ◽  
M.B Sultan ◽  
M Hanna
Keyword(s):  
Disease Severity ◽  
Nyha Class ◽  
Funding Source ◽  
Class Iii ◽  
Private Company ◽  
Risk Of Death ◽  
6Mwt Distance ◽  
All Cause Mortality ◽  
Amyloid Cardiomyopathy

Abstract Background In the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT), tafamidis was shown to be an effective treatment for patients with transthyretin amyloid cardiomyopathy (ATTR-CM). Further assessment of the efficacy of tafamidis in patients with more advanced ATTR-CM would aid treatment decisions. Purpose To characterize the benefits of tafamidis in patients with advanced ATTR-CM. Methods In ATTR-ACT, ATTR-CM patients were randomized to tafamidis (n=264) or placebo (n=177) for 30 months. Efficacy outcomes included all-cause mortality and frequency of cardiovascular (CV)-related hospitalisations. Key secondary endpoints were change from baseline to Month 30 in 6MWT distance and KCCQ-OS score. Efficacy assessments in NYHA Class III patients at baseline (n=141) were a pre-specified analysis. In a post-hoc analysis, mortality and CV-related hospitalizations were assessed in all patients grouped into quartiles of increasing disease severity based on 6MWT distance at baseline. Longer-term all-cause mortality (as of 1 Aug 2019) was assessed in NYHA Class III patients utilizing data from ATTR-ACT patients who enrolled in a long-term, extension study (LTE) and continued treatment with higher dose tafamidis (n=55; median treatment duration 51.6 months); or, if previously treated with placebo, started tafamidis treatment (placebo/tafamidis; n=63 [50.1 months]). Results In advanced ATTR-CM patients (NYHA Class III), tafamidis reduced the risk of death (HR [95% CI] 0.837, [0.541, 1.295], P=0.4253), and the decline in 6MWT distance (LS mean [SE], 31.6 (22.1) m; P=0.1526) and KCCQ-OS score (LS mean [SE], 13.1 (5.0); P=0.0090), vs placebo. Paradoxically, there was a higher frequency of CV-related hospitalizations with tafamidis (RR [95% CI] vs placebo, 1.411 [1.048, 1.900]). In all patients by 6MWT quartile, CV-related hospitalizations/year with tafamidis and placebo increased with disease severity, with the exception that placebo-treated patients in the highest severity quartile had fewer CV-related hospitalisations (0.73) than those in the third quartile (0.92). Mortality with tafamidis and placebo increased, and was greater with placebo, in every quartile (Figure). Survival (NYHA Class III patients in ATTR-ACT and LTE) was improved with high dose tafamidis with longer term follow-up (HR vs placebo/tafamidis [95% CI], 0.6569 [0.4175, 1.0336]; P=0.0692). Conclusions These analyses, including longer-term follow-up, demonstrate that patients with advanced ATTR-CM benefit from tafamidis. The decrease in CV-related hospitalisations in more severe patients treated with placebo suggests that the comparatively greater hospitalisation frequency in NYHA Class III patients treated with tafamidis is a consequence of their lower mortality rate. Figure 1 Funding Acknowledgement Type of funding source: Private company. Main funding source(s): This study was sponsored by Pfizer

NISAR-F SCORE: a simple risk stratification tool for patients implanted with cardiac resynchronization therapy

EP Europace ◽  
2021 ◽  
Vol 23 (Supplement_3) ◽  
Author(s):  
J Correia ◽  
L Goncalves ◽  
I Pires ◽  
J Santos ◽  
V Neto ◽  
...  
Keyword(s):  
Ejection Fraction ◽  
Cardiac Resynchronization Therapy ◽  
Cox Regression ◽  
Nyha Class ◽  
Prognostic Score ◽  
Roc Curves ◽  
Cardiac Resynchronization ◽  
Class Iii ◽  
Resynchronization Therapy

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Individualized estimation of prognosis after cardiac resynchronization therapy (CRT) remains challenging. Outcomes in this group of patients are influenced by multiple factors and a comprehensive and customized approach to estimate prognosis after CRT is lacking Aims To develop and validate a simple prognostic score for patients implanted with CRT (NISAR-F score), based on readily available clinical and echocardiographic variables to predict the combined endpoints of death or hospitalization in 24 months. Methods A single-centre retrospective study was conducted with inclusion of all consecutive patients who underwent CRT implantation between 2012 and 2019. Follow-up started after CRT implantation and ended upon death, hospitalization or 24 months after study entry. Survival analysis was performed using a multivariate Cox regression model, in order to analyze the effect on survival /hospitalization in 24 months of the following factors: age, gender, NYHA Class III-IV, ischemic heart failure, type 2 diabetes, arterial hypertension, dyslipidemia and ejection fraction &lt; 21%. According to the analysis, points were attributed to each factor. Afterwards, the NISAR-F score was calculated for each patient, summing the points of each variable. The authors finally created ROC curves for the NISAR-F score to predict the occurrence of the combined endpoint in 2 groups of patients: CRT responders (ejection fraction increase of at least 10% after CRT implantation) and CRT non-responders. The statistical analysis was performed in SPSS. Results 102 patients were included in the study (75.4% male, mean age 68 ± 10.46 years). 10(9.8%) of the patients were re-hospitalized and 8 (7.8%) died during the 24-month follow-up.  After calculating NISAR-F score for each patient, area under ROC curves were obtained. The analysis of the ROC curves allows us to confirm the good performance of the score created [responders group (AUC 0.812) vs non-responders (AUC 0.721)]. Conclusion The NISAR-F score is a useful tool to predict the combined endpoint (mortality and hospitalization in 24 months) after CRT implantation, in both responders and non-responders, revealing good performance of this new and simple score based only on clinical and echocardiographic variables.

Abstract 2068: Systematic Undersized Rigid Ring Decreases Recurrence Rate Following Repair of Ischemic Mitral Valve

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Raphaël Fontaine ◽  
Denis Bouchard ◽  
Philippe Demers ◽  
Raymond Cartier ◽  
Michel Carrier ◽  
...  
Keyword(s):  
Mitral Valve ◽  
Mitral Regurgitation ◽  
Recurrence Rate ◽  
Nyha Class ◽  
High Recurrence Rate ◽  
Class Iii ◽  
Term Survival ◽  
Rigid Ring

Introduction: Chronic ischemic mitral regurgitation (MR) has been associated with poor long-term survival. Suboptimal midterm results have been a growing concern in the surgical community. In recent years, our approach to repair those valves has evolved to a standardized technique using complete, rigid and small annuloplasty rings. This study aims to compare this systematic approach with our prior experience from 1996 –2001 where recurrent MR rate was high. Methods: 129 patients underwent repair for pure ischemic mitral valve regurgitation between 2002 and 2005 at our institution. Of these patients, 99 had clinical and echographic follow-up. These patients were compared to the 1996 –2001 cohort of 73 patients. Results: Preoperatively, 84% of patients were in NYHA class III or IV, 17% had moderate MR, 83% had moderate-severe to severe MR. Sixteen were redo operations, mostly of previous CABG. All patients except one were treated with a complete rigid ring (Annuloflo 46.5%, Physioring 34.9%, Etlogix 13.9%, others 3.8%). Ring size was: 24 (0.8%); 26 (55.8%); 28 (38%); or 30 (4.5%). Mortality was 8.5% at 30 days, 14.7% at 1 year and 17.8% at 2 years. Immediate postoperative regurgitation was absent or trace in all patients. Freedom from reoperation was 97%. Mean postoperative NYHA class was 1.15 at a mean follow-up of 28 months. Recurrent moderate mitral regurgitation (2+) was 15.34%, severe mitral regurgitation (3+ to 4+) was 13.4% at a mean follow-up of 16 months. In the 73 patients from the period 1996 –2001 at the same echo follow-up time, the moderate and severe recurrence were: 37% and 21%. The decrease in the recurrence rate was highly significant (p=0.001). Conclusion: A more standardized approach to ischemic mitral valve repair has improved the high recurrence rate previously reported by our group. Long-term follow-up is necessary to confirm these findings.

Outcomes of Patients Undergoing Primary Fontan Operation Beyond First Decade of Life

2017 ◽  
Vol 8 (4) ◽  
pp. 487-494 ◽  
Author(s):  
Sachin Talwar ◽  
Sukhjeet Singh ◽  
Vishnubhatla Sreenivas ◽  
Kulwant Singh Kapoor ◽  
Saurabh Kumar Gupta ◽  
...  
Keyword(s):  
Ventricular Dysfunction ◽  
Nyha Class ◽  
Fontan Operation ◽  
Functional Class ◽  
Early Mortality ◽  
Thromboembolic Events ◽  
Class Iii ◽  
Pleural Effusions ◽  
Nyha Functional Class

Objectives: Studies on older patients undergoing primary Fontan operation (FO) are limited, with conflicting results. We review our experience with these patients beyond the first decade of life. Patients and Methods: Between January 2000 and December 2014, a total of 105 patients ≥10 years of age (mean 15.6 ± 4.9, range 10-31, median 15 years) underwent primary FO without a prior bidirectional superior cavopulmonary anastomosis (Bidirectional Glenn [BDG]). Mean preoperative New York Heart Association (NYHA) class was 2.2 ± 0.57. Results: Operative procedure was extra-cardiac FO in 62 patients (8 were fenestrated). Forty-three had a lateral tunnel FO (26 were fenestrated). There were 11 (10.5%) early deaths. Fourteen of the 94 early survivors experienced prolonged pleural effusions, 7 had arrhythmias, and 2 had thromboembolic events. Two patients underwent Fontan takedown. On univariate analysis, NYHA functional class III, mean pulmonary artery (PA) pressure ≥15 mm Hg, hematocrit ≥60%, preoperative ventricular dysfunction, and atrioventricular valve regurgitation (AVVR) were associated with early mortality. Median follow-up was 78 (mean 88.9 ± 6.3) months. In 94 survivors, 6 (6.4%) late deaths were encountered. At last follow-up, 81 (86.2%) survivors were in NYHA class I. Actuarial survival was 84.7% ± 3.7% at 5, 10, and 15 years. Conclusion: Carefully selected adolescents and young adults can safely undergo the primary FO. However, persistent pleural effusions, arrhythmias, thromboembolic events, and the need for reoperation mandate regular follow-up in such patients. Preoperative NYHA functional class III, mean PA pressure ≧ 15 mm Hg, hematocrit ≥ 60%, ventricular dysfunction, and AVVR were associated with early mortality, suggesting that primary FO should be avoided in such patients.

Abstract 19346: Peak Oxygen Consumption Predicts Outcome in Hypertrophic Cardiomyopathy

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Carla Contaldi ◽  
Raffaella Lombardi ◽  
Alessandra Giamundo ◽  
Sandro Betocchi
Keyword(s):  
Heart Failure ◽  
Oxygen Consumption ◽  
Hypertrophic Cardiomyopathy ◽  
Nyha Class ◽  
Left Ventricular ◽  
Exercise Intolerance ◽  
Peak Oxygen Consumption ◽  
Class Iii ◽  
Asymptomatic Patients

Introduction: Peak oxygen consumption (VO 2 ) has a strong and independent prognostic value in systolic heart failure; in contrast no data support its prognostic role in hypertrophic cardiomyopathy (HCM). Hypothesis: We assess if peak VO 2 is a long-term predictor of outcome in HCM. Methods: We studied 92 HCM patients (40±15 years). Peak VO 2 was expressed as percentage (%) of the predicted value. Follow up was 76±57 months. The primary composite endpoint (CE) was atrial fibrillation, progression to NYHA class III or IV, myotomy-myectomy (MM), heart transplantation (HT) and cardiac death. An ancillary endpoint (HFE) included markers of heart failure (progression to NYHA class III or IV, MM and HT). Results: At baseline, 62% of patients were asymptomatic, 35% NYHA class II and 3% NYHA class III; 26% had left ventricular outflow tract obstruction. During follow up, 30 patients met CE with 43 events. By multivariate Cox survival analysis, we analyzed 2 models, using the CE, and in turn HFE. For CE, maximal left atrial diameter (LAD) (HR: 1.12; 95% CI: 1.04 to 1.22), maximal wall thickness (MWT) (HR: 0.14; 95% CI: 1.04 to 1.23) and % predicted peak VO 2 (HR: -0.03; 95% CI: 0.95 to 0.99) independently predicted outcome (overall, p<0.0001). For HFE, maximal LAD (HR:0.31; 95% CI: 1.09 to 1.70), MWT (HR: 0.35; 95% CI: 1.08 to 1.84) and % predicted peak VO 2 (HR: -0.06; 95% CI: 0.89 to 0.98) independently predicted outcome (overall, p<0.0001). Only 19% of mildly symptomatic or asymptomatic patients with % predicted peak VO 2 >80% had events, as opposed to 53% of them with % predicted peak VO 2 < 55% (p= 0.04). Event-free survival for both endpoints was significantly lower in patients with % predicted peak VO 2 < 55% as compared to those with it between 55 and 80 and >80% , Figure. Conclusion: In mildly or asymptomatic patients severe exercise intolerance may precede clinical deterioration. In HCM, peak VO 2 provides excellent risk stratification with a high event rate in patients with % predicted value <55%.

scholarly journals Potential Role and Prognostic Value of Erythropoietin Levels in Patients With Severe Aortic Stenosis Undergoing Transcatheter Aortic Valve Replacement

2020 ◽  
Vol 7 ◽  
Author(s):  
Silvia Mas-Peiro ◽  
Philipp C. Seppelt ◽  
Roberta De Rosa ◽  
Marie-Isabel Murray ◽  
Jörg Yogarajah ◽  
...  
Keyword(s):  
Aortic Stenosis ◽  
Prognostic Value ◽  
Severe Aortic Stenosis ◽  
Strong Predictor ◽  
Nyha Class ◽  
High Volume ◽  
Class Iii ◽  
Eligibility Criteria ◽  
Term Survival

Background: Both EPO levels and anemia have shown prognostic value in several cardiac disorders. An observational study with a prospective follow-up was performed to investigate their independent prognostic roles in severe aortic stenosis.Methods: An up to 36-month follow-up of consecutive patients with severe aortic stenosis undergoing TAVR in a high-volume center was performed. Patients with eGRF &lt;30 mL/min/1.73 m2 were excluded. EPO levels and/or anemia status and its association with mid-term mortality were assessed.Results: Out of 407, 360 met eligibility criteria. Median age was 83 years, with 71.4% having a NYHA class III/IV. Anemia was present in 51.9%, and iron deficiency in 52.8%. Median (IQR) EPO levels were 14.4 (9.30–24.30) mIU/mL. Median follow-up was 566 days. Anemia was associated with overall mortality (HR 2.40, 95% CI 1.51–3.80, p &lt; 0.001). Higher logEPO levels were associated with mid-term mortality (HR 4.05, 95% CI 2.29–7.16, p &lt; 0.001), even after adjusting for clinically and/or statistically relevant factors (multivariate HR 2.25, 95 CI 1.09–4.66, p = 0.029). Kaplan-Meier analyses showed early diverging curves for anemia vs. non-anemia, whereas curves for patients in various EPO level quartiles started to diverge at about 100 days, with differences consistently increasing during the subsequent entire follow-up period.Conclusions: Differently from anemia, which was a strong predictor for both early and late mortality in severe aortic stenosis after TAVR, independent prognostic value of EPO only emerged after post-TAVR recovery. EPO prognostic value was independent from anemia and mild-to-moderate renal dysfunction. High EPO levels could be useful to identify patients with severe aortic stenosis showing a compromised mid-term survival in spite of TAVR use and independently from early TAVR results.

P320Heart failure with mid-range (HFmrEF) or recovered (HFrecEF) ejection fraction: differential determinants of transition

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
R De Maria ◽  
F Macera ◽  
M Gorini ◽  
I Battistoni ◽  
M Iacoviello ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Ejection Fraction ◽  
Clinical Characteristics ◽  
Nyha Class ◽  
Multivariable Logistic Regression Analysis ◽  
Class Iii ◽  
Mild Disease ◽  
Lower Likelihood ◽  
History Of

Abstract Background Heart failure with mid-range ejection fraction (HFmrEF) has been identified as a multi-faceted phenotype that may encompass both patients with mild disease or those who from previous HFrEF recover EF (HFrecEF) Purpose To describe clinical characteristics and factors associated with phenotype transition at follow-up. Methods From 2009 to 2016, 1194 patients with baseline EF<50% and a second echocardiographic determination during clinically stability at a median of 6 months were enrolled in the IN-CHF Registry. Based on EF at enrollment, 335 (28%) had HFmrEF and 859 (72%) had HFrEF. We compared baseline clinical characteristics and predictors associated with follow-up reclassification to HFmrEF or full EF recovery Results When compared to HFrEF patients, those with HFmrEF had less often an ischemic etiology, advanced symptoms and a HF admission in the previous year. No other differences were found in clinical characteristics and drug therapy (Table). At a median follow-up of 6 months, 30% of HFrEF patients improved EF by 14 (9) units: 21% showed partial EF recovery (transition to HFmrEF) and 9% had full EF recovery. Conversely among HFmrEF patients 22% improved EF, by 9 (5) units, to full recovery, and 18% deteriorated by 1.5 (5.5) units sloping to HFrEF. By multivariable logistic regression analysis, variables associated with EF recovery at 6-month follow-up differed between baseline phenotypes. Within HFrEF, ischemic etiology (OR 0.46, 95% CI 0.33–0.64) and NYHA class III-IV symptoms (OR 0.57, 95% CI 0.38–0.68) were associated with a lower likelihood of EF recovery, while a history of HF<6 month correlated with a higher likelihood of EF recovery (OR 2.44, 95% CI 1.76–3.39). Within HFmrEF, while ischemic etiology (OR 0.66, 95% CI 0.19–0.68) was also associated with a lower likelihood of EF recovery, a history of atrial fibrillation at enrollment correlated with higher likelihood of EF recovery (OR 2.66, 95% CI 1.37–5.17) by 6 month-follow-up. At a median follow-up of 36+28 months mortality was 4.6% vs 6.9% in HFrecEF vs non-recovered patients (log rank p=0.08). Baseline characteristics HFrEF vs HFmrEF Conclusions HFmrEF patients showed a less severe clinical picture than HFrEF patients, but had EF recovery less often. EF improvement is negatively associated with ischemic etiology in both phenotypes, and positively associated with atrial fibrillation in HFmrEF and a short history of HF in HFrEF.

Increases In B-Type Natriuretic Peptide (BNP) During Treatment with Lenalidomide In AL Amyloidosis

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3021-3021
Author(s):  
Umit Tapan ◽  
David C Seldin ◽  
Kathleen T Finn ◽  
Salli Fennessey ◽  
Anthony C Shelton ◽  
...  
Keyword(s):  
Heart Failure ◽  
Congestive Heart Failure ◽  
Cardiac Involvement ◽  
Troponin I ◽  
Medical Center ◽  
Nyha Class ◽  
Early Time ◽  
Response To Therapy ◽  
Plasma Cell Dyscrasia ◽  
Al Amyloidosis

Abstract Abstract 3021 The combination of lenalidomide and dexamethasone can produce partial and complete hematologic responses in previously treated patients with AL amyloidosis (Blood 2007; 109: 492–496). Since this prospective study was initiated, NT-proBNP and BNP have been found to be useful biomarkers for cardiac involvement, prognosis, and response to therapy in AL amyloidosis patients. Here we report on the retrospective analysis of the prospectively collected data on changes in BNP during lenalidomide therapy on this trial. Increase in BNP was defined as > 30% increase from baseline value at enrollment on the trial after cycles 1 and 3. Patients with BNP of < 100 pg/mL at baseline, and after 1 and 3 cycles as well as patients in whom BNP levels were not measured were excluded in this analysis. Sixty-eight patients with AL amyloidosis were treated with lenalidomide and dexamethasone (ClinicalTrials.gov: NCT00091260) at Boston Medical Center. The median age was 64 years (range, 42 to 85); and 69% were male. Fifty-one patients (75%) had lambda clonal plasma cell dyscrasia, and 38 (56%) had cardiac involvement. All patients received lenalidomide and dexamethasone as described in our previous report. Twenty-four of the 68 total patients enrolled did not meet the eligibility to be included in this analysis due to either BNP levels of < 100 pg/mL at baseline and at 1 and 3 months after treatment or unavailability of BNP measurement after 1 or 3 cycles of lenalidomide. Therefore, 44 patients are included in this analysis. Thirty-eight patients (86%) had > 30% increase in BNP level from baseline after initiation of lenalidomide treatment. Of these 38 patients, 30 (79%) had an increase after 1 cycle and additional 8 (21%) patients after 3 cycles of lenalidomide. The mean dose of lenalidomide for patients with increase in BNP after 1 cycle was 15 mg (range, 5–25) and after 3 cycles was 10 mg (range, 5–15). Forty % (n=12/30) and 63% (n=5/8) of patients did not receive dexamethasone with lenalidomide when increase in BNP was seen after 1 and 3 cycles, respectively. Of the patients with increase in BNP, only 5 patients (13%) had worsening of renal function from baseline. Moreover, increase in BNP after 1 and 3 cycles occurred in 23 of 29 patients (79%) with cardiac involvement. Cardiac troponin I levels were not measured after 1 and 3 cycles of lenalidomide. All the patients with increase in BNP were asymptomatic without association of modification in NYHA class congestive heart failure. The median survival of these 44 patients is 53 months since initiation of lenalidomide therapy. At these early time pointsof 1 and 3 months, 20% (n=9/44) of patients had >50% improvement in serum free light chain levels, and 2% (n=1/44) of patients had improvement in BNP of 30% or more. In conclusion, BNP increased by > 30% in a substantial proportion of patients with AL amyloidosis during treatment with lenalidomide. The mechanism for asymptomatic rise in BNP is not clear; however, the temporal relationship with lenalidomide initiation, the relatively rapid increase, and the absence of other identifiable precipitants for most of the patients suggest that lenalidomide may be playing a role. Moreover, patients with AL amyloidosis receiving lenalidomide whose BNP rises should not be assumed to be failing therapy without other signs of disease progression, but should be monitored closely and treated as needed for signs or symptoms of congestive heart failure should they occur. Disclosures: Off Label Use: Use of lenalidomide in AL amyloidosis. Zeldis:Celgene Corp: Employment.

A Prospective Study of Treatment Outcomes in 179 Patients with Advanced Cardiac Stage STAGE IIIb Amyloidosis

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5357-5357
Author(s):  
Belen Sevillano ◽  
Ashutosh Wechalekar ◽  
Darren Foard ◽  
Carol Whelan ◽  
Marianna Fontana ◽  
...  
Keyword(s):  
Partial Response ◽  
Prospective Study ◽  
Treatment Outcomes ◽  
Cardiac Involvement ◽  
Left Ventricular ◽  
Stage Iiib ◽  
Stage Iii ◽  
Al Amyloidosis ◽  
Hematological Response ◽  
A Prospective Study

Abstract A PROSPECTIVE STUDY OF TREATMENT OUTCOMES IN 179 PATIENTS WITH ADVANCED CARDIAC STAGE IIIB AMYLOIDOSIS Authors: Belen Sevillano, Darren Foard, Carol Whelan, Mariana Fontana, Critina Quarta, Shameem Mahmood, Helen Lachmann, Julian Gillmore, Philip Hawkins and Ashutosh Wechalekar INTRODUCTION The prognosis of systemic light chain amyloidosis is determined by extent of cardiac involvement. The Mayo cardiac staging system (Dispenzieri et al JCO 2004) is widely used for prognosis and we defined a particularly poor prognostic subgroup within Mayo stage III patients (Wechalekar et al Blood, 121(17), 2013) characterized by NT-proBNP >8500 ng/L with a median survival of 4 months-stage IIIb disease. All such patients are excluded from clinical trials and treatment outcomes of this group are not known. We report the treatment outcomes of a cohort of stage IIIb cardiac AL patients prospectively followed up in the ALChemy study PATIENTS AND METHODS. All patients from the ALChemy study (a prospective observational study of all patients with AL amyloidosis undergoing chemotherapy) at the UK National Amyloidosis Centre (identified from first 1000 patients recruited into the study from 2009 to Jan 2015) with Mayo stage IIIb cardiac AL (defined as NT-proBNP >8500 ng/L and cardiac troponin T >0.035 μg/L) were included. All were treated according to nationally agreed protocols. Organ involvement and hematologic/amyloidotic organ responses were assessed according to 2010 amyloidosis consensus criteria. The primary outcome measure was overall survival (OS) and impact of hematological response on survival. Statistical analysis was undertaken using SPSS software package. Survival was assessed by the Kaplan-Meier method and compared by log-rank test. RESULTS A total of 179 patients were included. The median age was 65 yrs, 77 (43 %) were female and 102 (57 %) male. All patients had cardiac involvement, renal involvement was seen in 131 (73.2 %) and liver involvement in 28 (15.6 %). The median NT-proBNP was 19056 ng/L (range 8500 - 70084 ng/L). The median left ventricular (LV) wall thickness was 14.2 mm (range 11-22 mm) and median ejection fraction (EF) was 48.7 % (23-75 %). 34 % had dyspnea ≥ NYHA grade 3 and 16.8 % had ECOG performance status ≥3. Only 68 (38 %) patients managed a 6 min walk test and median distance was 130.5 m. 30 (17 %) patients died prior to treatment initiation. Initial treatment regimens were: Bortezomib combinations - 48 % (87); Thalidomide or Lenalidomide combinations in 28 % (51), alkylators based regimens - 5 % (9) and rituximab based in 1 %. The hematological best responses on an intention to treat basis were: complete response (CR) - 35w (20%), very good partial response (VGPR) 25 (13%), partial response (PR) 32 (18%) and no response (NR) 87 (47%) (NR included patients who died before treatment). The median OS for the cohort was 6 months (mo). Univariate and ROC analysis identified LVEF >55%, dFLC <400 mg/L and SBP >110 mm of Hg predictors of OS. The median OS was significantly better for patients with LVEF>55% (13 mo); for dFLC < 400 mg/L was 7 mo (vs. 3 mo for dFLC >400 mg/L); and for those with SBP > 110 mmHg was 10 mo (vs. 5 mo in those with lower SBP). Median OS for patients achieving a CR/VGPR at day 30 was 26 mo compared to 5 mo for patients with <VGPR at that time. The median OS for patients who finally achieved CR/VGPR was 38 mo, PR 7 mo and NR was 2.6 mo (log rank p<0.0001) (Fig 1). In a multivariate model, achieving a hematological CR/VGPR (HR 5.3), LVEF <55% (HR1.5), dFLC >400 mg/L (HR 1.3) and SBP <110 mm of Hg (HR 1.5) were independent predictors of outcomes. CONCLUSIONS: The survival of stage IIIb AL remains poor but has improved compared with historical reported series. The survival of patients who achieve a CR or VGPR is over 3 years. Early achievement of ≥VGPR, as early as end of cycle 1, seems to predict for a better survival challenging the practice of treating stage III patients with "low" dose chemotherapy which often leads to slower clonal responses. This study confirms that, even in this advanced group of patients, a rapid hematological response will translate into improved outcomes. Since most non-responders to the first 1 or 2 cycles succumb to progressive disease, prospective studies are urgently needed to design rapidly effective well tolerated regimes possibly with combination of anti-amyloid therapy. Disclosures No relevant conflicts of interest to declare.

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