scholarly journals Cardiac involvement Is Underdiagnosed in Patients with Biopsy-Proven Systemic AL Amyloidosis

2016 ◽  
Vol 6 ◽  
Author(s):  
Haoyi Zheng ◽  
Amitabha Mazumder ◽  
Stuart Katz
Keyword(s):  
Clinical Diagnosis ◽  
Cardiac Amyloidosis ◽  
Cardiac Involvement ◽  
Clinical Care ◽  
Response To Therapy ◽  
Cardiac Response ◽  
Al Amyloidosis ◽  
Limited Data ◽  
Nccn Guidelines

<p><strong>Background</strong>: Clinical recognition of cardiac involvement and cardiac response to therapy is an important element of clinical care in patients with AL amyloidosis. The new criteria including NT-proBNP, troponin, and echocardiography for assessment of cardiac involvement in patients with systemic AL amyloidosis were proposed in 2004, but there are limited data on the utilization of these in clinical practice</p><p><strong>Methods</strong>: We retrospectively reviewed the clinical data of 28 patients with AL amyloidosis. Clinical diagnosis of cardiac amyloidosis was based on medical record documentation of symptomatic heart failure without other causes. Then we use the criteria from the current NCCN Guidelines to reassess cardiac involvement.</p><p><strong>Results</strong>: 14 cases (50%) had clinical diagnosis of cardiac amyloidosis at the time of diagnosis and also met the NCCN criteria. An additional 6 cases without clinical diagnosis of cardiac amyloidosis met the NCCN criteria. In total, 20 patients (71.4%) met the NCCN criteria for cardiac involvement. No routine follow-up testing with echocardiography and biomarkers was documented during treatment for any of the patients.</p>

A European Collaborative Study of Treatment Outcomes In 428 Patients with Systemic AL Amyloidosis

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 988-988 ◽  
Author(s):  
Ashutosh D Wechalekar ◽  
Efstathios Kastritis ◽  
Giampaolo Merlini ◽  
Philip N Hawkins ◽  
Meletios A. Dimopoulos ◽  
...  
Keyword(s):  
Cardiac Amyloidosis ◽  
Cardiac Involvement ◽  
Median Number ◽  
Cardiac Response ◽  
Al Amyloidosis ◽  
Line Treatment ◽  
End Of Treatment ◽  
Significant Difference ◽  
Organ Response

Abstract Abstract 988 The treatment of patients with systemic AL amyloidosis remains challenging. Cyclical combination chemotherapy is used in majority of patients but a report that I.V. melphalan-dexamethasone may not overcome the poor prognosis for cardiac amyloidosis (Deitrich S et al, Blood, 116, 2010) has fuelled the controversy about best front line treatment. We report outcomes of 428 patients treated with oral cyclophosphamide thalidomide dexamethasone (CTD), oral melphalan dexamethasone (M-dex), bortezomib dexamethasone with or without an alkylator (BD), cyclophosphamide-lenalidomide-dexamethasone (CLD) or stem cell transplant (ASCT) as first line treatment for systemic AL amyloidosis assessed at three large European amyloid centres in London (UK), Pavia (Italy) and Athens (Greece) between 2003–2010. Patients with a full baseline data set were included in the study. Clonal and organ responses were defined according to the international amyloidosis consensus statement (Gertz et al 2005) and responses were assessed at 6 months or at the end of treatment. dFLC (difference between involved and uninvolved free light chain (FLC)) was used to assess the absolute FLC change after treatment. 204 (48%) received M-dex, 155 (36%) received CTD, 13 (3%) received ASCT, 28 (7%) received BD and 25 (6%) received CLD. The median number of cycles received was 5 for all regimens. 257 (60%) had cardiac involvement, 325 (76%) had renal and 59 (14%) had liver involvement. Cardiac involvement by regime was: BD 75%, CLD 68%, M-dex 65%, CTD 45% and ASCT 23%. 30 (7%) died within six months of diagnosis. The median number of organ involved was 2 (range 1–5) with ECOG performance status ≥2 in 123 (28%). 98 (23%) patients achieved a complete response (CR), 175 (41%) achieved a partial response (PR) and 125 (29%) did not respond to treatment. A haematological CR/PR was seen, respectively, in 22%/41% treated with CTD, 26%/44% with M-dex, 23%/46% with ASCT, 39%/42% with BD and 4%/44% with CLD. There was significantly greater reduction in dFLC after BD (median reduction 91% over starting value) compared to CTD (median 81%; p = 0.006), M-Dex (median 83%; p = 0.004) and CLD (median 72%; p = 0.03). There was no significant difference in the median dFLC reduction between patients treated with CTD and M-Dex. 100/325 (30%) had a renal organ response, 17/59 (29%) had a hepatic response and 24/257 (9%) had a cardiac response, and 61 (16%) had a cardiac response by NT-proBNP criteria. The organ and NT-proBNP responses respectively were highest in the cohort treated with BD (53% and 32%) followed by CTD (38% and 12%), ASCT (30%), M-dex (23% and 19%) and CLD (12% and nil). CTD achieved significantly better organ responses compared to M-dex (p=0.0024). At median follow up of 29 months, median overall survival (OS) for the whole cohort has not been reached with 2, 3 and 4 year estimated survival of 75%, 65% and 61%, respectively. When patients with cardiac involvement were considered, those achieving a CR have not reached median OS with an estimated 3 year survival of 89%, those with PR had an estimated median OS of 50 months and the non-responders had a median OS of 21 months. Detailed comparison by Mayo stage will be presented. There was no significant difference in the OS of patients treated with CTD or M-Dex (as compared directly or by centre). In summary, outcome of patients with AL amyloidosis across three major European centres appears comparable. BD treatment achieves significantly lower end of treatment dFLC values compared to CTD, M-dex, ASCT or CLD – which importantly translates into an organ response in over half of all patients receiving BD compared to a third of those treated with CTD and quarter of those with M-dex and further follow up may yet reveal survival differences. Organ responses appear significantly better with CTD compared to M-dex – possibly due to more rapid response to CTD since the end of treatment dFLC values are not significantly different - although this does not translate into a survival advantage. Depth of clonal response appears to be directly linked to improvement in survival of patients with cardiac amyloidosis (including in patients treated with CTD and M-dex) and organ response in general. This study supports the rational for doing urgent phase III studies confirming benefits of bortezomib combination chemotherapy for upfront treatment in AL amyloidosis and the benefit of rapid deep clonal responses in cardiac amyloidosis irrespective of the regimen. Disclosures: Off Label Use: Thalidomide, bortezomib, lenalidomide. Dimopoulos:Celgene: Honoraria; Othro Boitech: Honoraria.

Long Term Follow up of the Combination of Bortezomib with Dexamethasone as Initial Treatment for AL Amyloidosis

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3048-3048
Author(s):  
Efstathios Kastritis ◽  
Maria Roussou ◽  
Magdalini Migkou ◽  
Maria Gavriatopoulou ◽  
Constantinos Pamboukas ◽  
...  
Keyword(s):  
Initial Treatment ◽  
Cardiac Amyloidosis ◽  
Cardiac Involvement ◽  
High Dose ◽  
Al Amyloidosis ◽  
Long Term Follow Up ◽  
Organ Response ◽  
High Dose Melphalan

Abstract Abstract 3048 Until recently, patients with AL amyloidosis had limited treatment options, especially those who were not candidates for high dose therapy, those with severe cardiac involvement or patients who relapsed after initial treatment or never responded to first line alkylators with steroids. Bortezomib (B) with dexamethasone (D) has shown significant activity in patients with AL amyloidosis in patients who relapsed or even those who were refractory to initial treatment. We and others have presented data indicating that BD is active in newly diagnosed patients with AL, inducing responses rapidly but also associated with high rates of complete responses. However, data about long-term follow-up of these patients are limited. Thus, we updated a series of 24, previously untreated patients who received frontline BD. In all patients, treatment started with B at a dose of 1.3 mg/m2 on days 1, 4, 8 & 11 and D was given for 4 consecutive days at a dose of 40 mg per day (days 1–4), every 21 days for up to 6 cycles. The median age of these patients was 70 years (range 42–82) and 46% were males. The median number of involved organs was 2; heart was involved in 83% and kidneys in 63%. Fifty-seven percent were Mayo stage II and 26% were Mayo stage III while 67% had impaired ECOG performance status ≥ 2. The first patient started treatment with BD on September 2005. A median of 5 cycles of BD was given (range 1–6) and 57% of patients received the planned 6 cycles. On intent to treat and according to criteria published by Gertz et al in 2005, 77% of patients achieved a hematologic response including 36% with a hematologic CR. Most of the responses occurred after the first cycle of BD (median time to first response <1 month), while a median of two cycles of BD was needed for CR (median time to CR was 42 days, range 21–84). In 54% of patients an organ response was recorded: 47% of patients with a cardiac involvement achieved a cardiac response and 77% had a reduction of NTproBNP ≥ 30% (which was at least 300 pg/ml), while 60% of patients with a kidney involvement achieved an organ response. Three patients received high dose melphalan with autologous stem cell transplant (HDM-ASCT) after they had completed 6 cycles of BD, 2 while in CR and one in PR. All these 3 patients had achieved organ responses before ASCT. The median follow up for all patients is 31 months. Thirteen patients (54%) have died; most of them due to complications of cardiac amyloidosis and the median survival is estimated to exceed 36 months (patients who underwent ASCT were censored at the time of HDM). Baseline NT-proBNP was the most significant factor independently associated with survival. There were no differences in the baseline characteristics of patients who achieved CR compared to those who achieved a PR as best hematologic response. The median follow up for patients who achieved a CR is 31 months (range 2–55 months). One patient died early due to complications of cardiac amyloidosis, while she had achieved a CR. Among the rest of the patients who achieved a CR but did not receive HDM, all remain alive and without progression for a median of 32 months. Similarly none of the patients who received HDM has relapsed. Among patients who achieved a PR as their best response, 4 (50%) have relapsed and the median progression free survival (PFS) for these patients is 9 months and their median survival is 34 months. In conclusion, BD induces high rates of CRs, in unselected, patients with previously untreated AL amyloidosis, most of whom had features of advanced disease and elevated cardiobiomarkers. i.e. patients that may be excluded form clinical trials. The severity of cardiac involvement remains the most important prognostic factor despite the rapid responses and the high rates of hematologic CRs. It is also of interest to note that CRs may persist even in patients who did not receive any alkylating agents or consolidation with high dose melphalan. A CR is associated with improved survival and should be the primary goal of treatment in patients with AL. Our data indicate that primary treatment with bortezomib based regimens should be evaluated in a phase III trial. Disclosures: Dimopoulos: Ortho-Biotech: Honoraria; Celgene: Honoraria; Millennium: Honoraria.

scholarly journals Free Light Chain Burden and Elevated Alkaline Phosphatase Identify Patients with Non-Cardiac AL Amyloidosis with Poor Outcome

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3361-3361
Author(s):  
Giovanni Palladini ◽  
Paolo Milani ◽  
Andrea Foli ◽  
Giampaolo Merlini
Keyword(s):  
Alkaline Phosphatase ◽  
Partial Response ◽  
Cause Of Death ◽  
Cardiac Amyloidosis ◽  
Cardiac Involvement ◽  
Stage I ◽  
Liver Involvement ◽  
Al Amyloidosis ◽  
Heart Involvement

Abstract Background. The prognosis of patients with AL amyloidosis is mainly driven by the severity of heart involvement. Cardiac amyloidosis is being extensively studied, and accurate staging systems have been developed to identify patients with different degrees of heart dysfunction who are candidates for different treatment approaches. However, little is known on the outcome of patients without heart involvement who are generally considered low-risk. In the present study we evaluated factors affecting survival of patients with non-cardiac AL amyloidosis. Patients and Methods. The subjects (n=135) without cardiac involvement (NT-proBNP <332 ng/L and mean left ventricular wall thickness at echocardiography £12 mm) and with normal troponin (Mayo Clinic stage I) were selected form the prospectively maintained database including 748 consecutive, previously untreated patients with AL amyloidosis diagnosed at our center between 2004 and 2012. Results. Median age was 61 years (range 39-80 years). Involved organs were kidney (111, 82%); with median (range) proteinuria 7.2 g/24h (0.5-23.5 g/24h) and creatinine 1.1 mg/dL (0.5-4.4 mg/dL); soft tissues (21, 16%); liver (18, 13%), with median alkaline phosphatase (ALP) 2.3 times the upper reference limit (range 1.6-7.5 times u.r.l.); peripheral nervous system (13, 10%); gastrointestinal (GI) tract (10, 7%). One hundred seven patients (79%) had more than one organ involved. Median (range) bone marrow plasma cell infiltrate was 10% (2-29%) and dFLC (difference between involved and uninvolved free light chains) 70 mg/L (0-5721 mg/dL). Fifty-two patients (38%) were treated with melphalan / dexamethasone (MDex), 42 (31%) with bortezomib-based regimens, 14 (10%) underwent stem cell transplant (ASCT), 13 (10%) received thalidomide-based regimens, and the remaining patients received treatment for IgM clones or high-dose dexamethasone alone. After a median follow-up of living patients of 51 months, 23 patients (17%) died. Survival at 5 years was 82%. Twelve patients (52%) died a cardiac death (heart failure in 8 cases, sudden death in 4), after having developed cardiac involvement. All of them had baseline dFLC >100 mg/L. In these subjects the median NT-proBNP concentration at last assessment was 2401 ng/L, with a median 1646% increase compared to baseline. Of them 7 had failed to respond to frontline therapy, and the remaining had progressed after an initial partial response (PR, 3 cases) or very good partial response (VGPR, 2 cases). Eight patients (35%) died of liver failure. Six satisfied the criteria for liver involvement at baseline, and 2 developed hepatic amyloidosis during the follow-up, but had elevated ALP at baseline (1.3 and 1.4 times the u.r.l., respectively). Among them, 5 were non-responders to first-line therapy, and 3 had relapsed after PR (1) and VGPR (2). One patient died due to GI bleeding during ASCT. In the remaining 2 patients the causes of death were not directly related to the disease: myelodysplasia (5.9 years after having achieved VGPR with 6 cycles of MDex), and colorectal cancer (6.5 years after diagnosis). Only the two deaths that were not disease-related occurred in patients who presented with normal ALP and dFLC <100 mg/L (Figure). Elevated ALP (HR 5.11, P<0.001) and dFLC (HR 4.79, P<0.001) were independent prognostic factors at multivariate analysis. Conclusion. This is the first study specifically addressing the outcome of patients with non-cardiac AL amyloidosis. Cardiac dysfunction after development of heart involvement remains the first cause of death also in patients who do not have cardiac involvement at diagnosis. Notably, fatal cardiac amyloidosis occurred only in patients in whom dFLC was >100 mg/L at diagnosis. Progressive liver involvement emerges as a significant cause of death in Stage I AL patients, and is predicted by elevated ALP. Patients with non-cardiac AL who have high dFLC and/or ALP should be treated aggressively to prevent the onset of terminal organ damage. Figure Figure. Survival of patients with non-cardiac AL amyloidosis according to baseline dFLC and alkaline phosphatase Disclosures Merlini: Millennium Takeda: Honoraria.

Abnormal NT-ProBNP in AL Amyloidosis Patients without Cardiac Involvement at Diagnosis - A Predictor of Subsequent Cardiac Involvement.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1500-1500
Author(s):  
Ashutosh D. Wechalekar ◽  
Helen J. Lachmann ◽  
Julian D. Gillmore ◽  
Philip N. Hawkins
Keyword(s):  
Cardiac Amyloidosis ◽  
Cardiac Involvement ◽  
Myocardial Dysfunction ◽  
Posterior Wall ◽  
Left Ventricular ◽  
Al Amyloidosis ◽  
International Consensus ◽  
Cardiac Amyloid ◽  
Significant Difference

Abstract Cardiac involvement in AL amyloidosis is associated with a poor prognosis and greatly increased treatment related morbidity and mortality, and regression of cardiac amyloid deposits is extraordinarily slow following chemotherapy that suppresses the underlying aberrant light chain production. Diagnosis of cardiac amyloidosis is normally made by echocardiography, by which time significant diastolic dysfunction has usually developed. Atrial natriuretic peptides (ANP, BNP and its N-terminal fragment NT-ProBNP) are useful in early diagnosis of myocardial dysfunction. Serum NT-ProBNP concentration has been reported to be a promising marker of cardiac dysfunction in AL amyloidosis, and patients with normal NT-ProBNP values at diagnosis have superior outcomes. We report here the outcome of patients attending the UK National Amyloidosis Centre (NAC) who had elevated NT-ProBNP at diagnosis of AL amyloidosis but who did not have accompanying evidence of cardiac involvement using conventional consensus criteria. To exclude the confounding effect of renal failure which is associated with substantial elevation of NT-ProBNP, we studied patients with serum creatinine &lt;150 μmol/L and creatinine clearance of &gt;50ml/min at diagnosis in whom there was less than 10% change in renal function after treatment. AL type amyloidosis was confirmed in all patients histologically with corroborating genetic studies to robustly exclude hereditary amyloidosis as indicated. Organ involvement and responses/progression were defined according to recent international consensus criteria (Gertz et al 2005). 102 patients who had no evidence of cardiac involvement by these conventional parameters and who otherwise conformed with our study criteria were identified. Median creatinine was 87 μmol/L (44–128), albumin 33g/L (10–65), bilirubin 7 μmol/L (1–65) and alkaline phosphatase 89 units/L (36–2649). The median interventricular septal and left ventricular posterior wall thickness was 9 mm (7–11 mm). 62 (61%) patients had NT-ProBNP ≤ 35pMol/L at diagnosis while 40 (39%) had NT-ProBNP of &gt;35 pMol/L. There was no significant difference in the baseline characteristics of either group. 5 patients in each group did not respond to the initial chemotherapy (p=0.46). With median follow-up of 60 months, 19/40 (47%) of patients with NT-ProBNP &gt;35pMol/L at diagnosis developed evidence of cardiac involvement compared to only 6/62 (10%) of whose baseline NT-ProBNP was ≤ 35 pMol/L (p&lt;0.001). The Kaplan-Meier estimated median overall survival has not been reached for either group but the estimated 7 year survival was significantly better in the group with NT-ProBNP of ≤35pMol/L compared to those with greater values (92% vs. 82%, p=0.03). In conclusion, these preliminary findings suggest that patients who have elevated NT-ProBNP concentration but no conventional evidence of cardiac involvement at diagnosis of AL amyloid appear to be at greater risk of developing cardiac amyloidosis during follow-up, and have a poorer prognosis. It reasonable to speculate that such patients have early cardiac involvement at diagnosis that cannot be identified by conventional non-invasive methods, and that their risk of subsequently developing clinically significant cardiac amyloidosis may be reduced by striving to achieve complete remission of their underling clonal plasma cell disease.

Abstract 18297: Clinical and Prognostic Utility of Cardiac Magnetic Resonance Imaging in Multiple Myeloma Patients With Suspected Amyloidosis

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Sabha Bhatti ◽  
Evan Watts ◽  
Fahd Syed ◽  
Abdul Hakeem
Keyword(s):  
Magnetic Resonance Imaging ◽  
Multiple Myeloma ◽  
Cardiac Mri ◽  
Cardiac Amyloidosis ◽  
Cardiac Involvement ◽  
Al Amyloidosis ◽  
Resonance Imaging ◽  
Prognostic Utility

Background: Upto 30% of patients with multiple myeloma have AL amyloidosis and cardiac involvement is associated with worse outcomes in these patients. Traditional screening modalities including EKG, echocardiography and biomarkers have limited value. The aim of this study was to evaluate the role of “screening” cardiac MRI in a large multiple myeloma population at a large specialized referral center. Methods & Results: 164 consecutive patients with multiple myeloma who underwent cardiac MRI between 6/2005 and 10/2011 were enrolled in this study. Primary endpoint was all cause death. Clinical, EKG, echocardiographic, biomarker and MRI predictors for death were analyzed. Mean age of population was 63+10 years, 40% females and 16% African Americans. 30% of the population had MRI evidence of cardiac involvement. There were 26 patients who had biopsy proven systemic amyloidosis, of whom 62% showed cardiac involvement on MRI. 81% patients with confirmed cardiac amyloidosis on endomyocardial biopsy had typical MR pattern of cardiac involvement. During a median follow up period of 702 days (mean 1019 (950) days), there were 59 deaths (36%). Amyloid pattern on cardiac MRI (OR 2.19), elevated BNP and increased LV wall thickness on MRI were significant predictors of mortality . (All p<0.05) Conclusions: This is the largest study to date evaluating the role of cardiac MRI in multiple myeloma patients with suspected cardiac amyloidosis. Cardiac MRI is a clinically robust tool for risk stratification of this subset of patients.

scholarly journals Improvement in Global Longitudinal Strain (GLS) Correlates with NT-Probnp Response in Patients with Cardiac Amyloidosis Treated on a Phase 1b Study of Anti-Amyloid Mab Cael-101

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 958-958 ◽  
Author(s):  
Divaya Bhutani ◽  
Siyang Leng ◽  
Andrew Eisenberger ◽  
Mathew S. Maurer ◽  
Sofia Shames ◽  
...  
Keyword(s):  
Research Funding ◽  
Cardiac Amyloidosis ◽  
Longitudinal Strain ◽  
Cardiac Involvement ◽  
Pearson Correlation ◽  
Global Longitudinal Strain ◽  
Cardiac Response ◽  
Al Amyloidosis ◽  
Amyloid Deposits ◽  
Phase 1B

Abstract Background: Cardiac AL amyloidosis continues to have poor prognosis with median survival of less than a year from diagnosis and only 3 months in patients with cardiac stage 3b disease (1). Targeting the underlying plasma cell clone can clear circulating light chains but cannot remove deposited protein in the organs. CAEL-101 (11-1F4 mAb) is a monoclonal IgG1 antibody that directly binds to a conformational epitope present on both human kappa and lambda light-chain amyloid fibrils. In preclinical studies the antibody was able to localize to the amyloid tissue and led to decrease in size as well as elimination of the amyloid protein (2). An open-label phase 1b clinical trial of the CAEL-101 showed a promising organ response rate of 63% (3). Global Longitudinal Strain (GLS) is a sensitive measure of functional impairment in cardiac AL Amyloidosis, and may predict survival over and above that of cardiac biomarkers (4). Here, we evaluated the effects of CAEL-101 on the myocardial function using GLS in correlation with NT-proBNP in patients with cardiac amyloidosis treated with CAEL-101. Methods: Patients with relapsed/refractory AL amyloidosis were enrolled and treated in a phase 1b study (N=19) using the anti-amyloid mAb CAEL-101. CAEL-101 was administered weekly for 4 weeks with sequential doses of 0.5, 5, 10, 50, 100, 250 and 500 mg/m2 in a dose-escalation design. All patients underwent transthoracic echocardiograms at screening and 12 weeks. GLS was measured using speckle-tracking (TomTec-Arena 1.2, Germany) and calculated as an average of 4-, 2-, and 3- chamber based measurements. Paired student's t-test was used to compare echocardiographic variables at screening and 12 weeks after therapy start with CAEL-101. GLS was correlated with NT-proBNP using Pearson correlation coefficient. Results: The median age of patients (N=19) was 63 years with 68% male and 32% female. Ten out of 19 patients had cardiac involvement with a median NT-proBNP of 1186 (range 699-3964) at screening. Six out of 10 patients (60%) with cardiac involvement met cardiac response criteria by having a decrease in NT-proBNP >30% (3). Among echocardiographic parameters, mean GLS improved significantly in 9/10 patients from -15.58 ± -4.14% at screening to -17.37 ± -3.53% at week 12, p = 0.004 (Figure 1) of the trial. One patient who did not have improvement in GLS was dosed at low dose level 2 (5mg/m2) in the study. Under the null hypothesis, the probability of 9 or more patients improving without drug effect, is ~0.0107, suggesting that improvement of GLS in 9 of 10 is a highly unlikely outcome unless the there is a drug association. In contrast to the improved GLS in cardiac patients, CAEL-101 had no significant effect (p=0.4829) on GLS in the 9 patients without cardiac involvement (GLS -22.77 ± -3.12 at screening and -22.36 ± -3.02 at end of treatment), suggesting a specific effect of CAEL-101 on cardiac amyloid deposits (Figure 2 and Table 1). Pearson correlation coefficient between NT-proBNP response and GLS response (in 8 cardiac evaluable patients) was 0.345, further confirming the efficiency of Cael-101 in amyloid resolution resulting in structural remodeling of the heart muscle. Conclusion: Improvement in GLS correlates with improvement in NT-proBNP in in patients with cardiac AL Amyloidosis treated with CAEL-101. The short timeframe in which the improvement of the GLS occurred (12 weeks after entering the trial) suggests that this effect is Ab related and GLS along with NT-proBNP should be evaluated in larger studies as markers for early cardiac response in patients with AL Amyloidosis. References:Wechalekar AD, Schonland SO, Kastritis E et al. A European collaborative study of treatment outcomes in 346 patients with cardiac stage III AL amyloidosis. Blood.2013;121(17):3420-7.Wall JS, Kennel SJ, Stuckey AC et al. Radioimmunodetection of amyloid deposits in patients with AL amyloidosis. Blood. 2010 Sep 30;116(13):2241-4.Edwards CV, Gould J, Langer AL et al. Final Analysis of the Phase 1a/b Study of Chimeric Fibril-Reactive Monoclonal Antibody 11-1F4 in Patients with Relapsed or Refractory AL Amyloidosis. Blood 2017 130:509.Salinaro F, Meier-Ewert HK, Miller EJ et al. Longitudinal systolic strain, cardiac function improvement and survival following treatment of light-chain (AL) cardiac amyloidosis. Eur Heart J Cardiovasc Imaging.2017 Sep 1;18(9):1057-1064. *Dr. Lentzsch recused herself from the Phase 1a/b trial in 11/2017. Disclosures Maurer: Glaxo Smith kline: Other: personal fees ; Eidos: Other: Personal fees, Research Funding; Pfizer: Other: Personal fees, Research Funding; Prothena: Research Funding; Alnylam: Research Funding; Ionis: Other: Personal fees, Research Funding; Akcea: Other: Personal fees. Lentzsch:BMS: Consultancy; Caelum Biosciences: Consultancy, Other: Dr. Lentzsch recused herself as an investigator from the Phase 1a/b trial testing CAEL-101 in 11/2017., Patents & Royalties: Shareholder for Caelum Biosiences; Bayer: Consultancy; Janssen: Consultancy.

scholarly journals Diagnostic approach to light-chain cardiac amyloidosis and its differential diagnosis

2018 ◽  
Vol 49 (1) ◽  
pp. 9-14
Author(s):  
Monika Adamska ◽  
Anna Komosa ◽  
Tatiana Mularek ◽  
Joanna Rupa-Matysek ◽  
Lidia Gil
Keyword(s):  
Differential Diagnosis ◽  
Light Chain ◽  
Cardiac Amyloidosis ◽  
Cardiac Involvement ◽  
Diagnosis And Treatment ◽  
Diagnostic Approach ◽  
Al Amyloidosis ◽  
Delay In Diagnosis ◽  
Light Chain Amyloidosis ◽  
Novel Approaches

AbstractCardiac amyloidosis is a rare and often-misdiagnosed disorder. Among other forms of deposits affecting the heart, immunoglobulin-derived light-chain amyloidosis (AL amyloidosis) is the most serious form of the disease. Delay in diagnosis and treatment may have a major impact on the prognosis and outcomes of patients. This review focuses on the presentation of the disorder and current novel approaches to the diagnosis of cardiac involvement in AL amyloidosis.

scholarly journals Multimodality imaging can shift the clinical approach and prognosis of a patient: from heart failure and angina to cardiac amyloidosis

2021 ◽  
Vol 31 (1) ◽  
pp. 103-110
Author(s):  
Alexandra Maria Chitroceanu ◽  
Alina Ioana Nicula ◽  
Roxana Cristina Rimbas ◽  
Mihaela Andreescu ◽  
Cristina Popp ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Amyloidosis ◽  
Multimodality Imaging ◽  
Clinical Status ◽  
Decompensated Heart Failure ◽  
Response To Therapy ◽  
Al Amyloidosis ◽  
Clinical Approach ◽  
Non Invasive ◽  
Life Threatening

AL (light chain) amyloidosis is a life threatening disease. Untreated patients with involvement of the heart, a condition known as cardiac amyloidosis (CA), tend to have the most rapid disease progression and worst prognosis. Therefore, it is essential to early recognize the signs of symptoms of CA, and to identify the affected individuals with readily available non-invasive tests, as timely therapy can prolong life. Different imaging tests are used to diagnose and stratify the risk of the disease noninvasively, and to follow-up of the disease course and response to therapy. In this light, we present a case of a woman with cardiovascular risk factors, initially admitted for typical angina and decompensated heart failure (HF), who was later diagnosed with AL amyloidosis with cardiac involvement, by using multimodality imaging assessment in a step-by-step fashion. This changed completely the prognosis of the patient. Timely chemotherapy and stem cell transplantation led to an improvement in clinical status, biomarkers, and in a regression of amyloid myocardial infi ltration showed by imaging.

scholarly journals The prevalence of cardiac sarcoidosis is underestimated: [18F]FDG-PET is the answer

2021 ◽  
Vol 22 (Supplement_3) ◽  
Author(s):  
J Borges-Rosa ◽  
M Oliveira-Santos ◽  
R Silva ◽  
J Lopes De Almeida ◽  
L Goncalves ◽  
...  
Keyword(s):  
Heart Failure ◽  
Fdg Pet ◽  
Cardiac Involvement ◽  
Cardiac Sarcoidosis ◽  
Clinical Manifestations ◽  
European Population ◽  
Response To Therapy ◽  
Histological Diagnosis ◽  
18F Fdg

Abstract Funding Acknowledgements Type of funding sources: None. Background Overt cardiac involvement is reported in 5% of patients with sarcoidosis, although autopsy and imaging studies suggest higher prevalence, worldwide variation. The role of 18F-fluorodeoxyglucose positron emission tomography ([18F]FDG-PET) in non-invasive diagnosis and follow-up has increased in the last decade. Purpose Our goal is to describe the prevalence, clinical manifestations and outcomes of cardiac sarcoidosis (CS), diagnosed through [18F]FDG-PET, in a southern European population. Methods We included all patients with histological diagnosis of extracardiac sarcoidosis screened with [18F]FDG-PET between 2009 and 2020. We collected data on clinical manifestations, cardiac magnetic resonance (CMR) results, and mortality outcomes and compared those with and without cardiac involvement. We applied the criteria for the diagnosis of CS from Heart Rhythm Society. Results Of the 400 patients screened with [18F]FDG-PET, 128 had a histological diagnosis of extracardiac sarcoidosis (54.7% females, mean age 51.0 ± 14.2 years). None underwent endomyocardial biopsy. Ten patients had a pattern of [18F]FDG uptake consistent with CS defined as diffuse (n = 5), focal (n = 3), and focal on diffuse (n = 2). Of the 128 patients, 14 also underwent CMR, which identified 2 subjects with positive findings in both modalities and 3 additional patients: focal (n = 1), multifocal mid-wall (n = 2), focal mid-wall (n = 2), and multifocal subepicardial (n = 1) delayed gadolinium enhancement. Overall, 13 patients (10.2%) fulfilled the criteria for probable CS (53.8% female, mean age 56.2 ± 12.6 years), all with multiorgan involvement, mostly lung and lymph nodes (each 92%), followed by skin and central nervous system (each 15%). Median left ventricle ejection fraction was 62% [55-65] and there were cardiac manifestations of CS in 6 patients (46%): sick sinus syndrome (n = 2), complete heart block (n = 1), frequent premature ventricular complexes (n = 1), ventricular tachycardia plus heart failure (n = 1), and bifascicular block plus heart failure (n = 1). Eleven patients (85%) with probable CS were medicated with immunosuppressant drugs: corticosteroids (n = 9), methotrexate (n = 4), and azathioprine (n = 2). Four patients with previous [18F]FDG screening were revaluated after treatment, each showing no cardiac uptake.  After a mean follow-up of 4.0 ± 1.0 years, mortality was three-fold higher in patients with cardiac involvement, despite the absence of statistical significance (15% vs. 5%, P = 0.151). Conclusions In a southern European population with histological extracardiac sarcoidosis, the prevalence of cardiac involvement was 10.2%, most asymptomatic. [18F]FDG-PET improves the diagnostic yield and plays an important role in monitoring response to therapy. The higher mortality trend in those with CS needs to be ascertained in longer follow-up.

scholarly journals Effectiveness of Bortezomib in Cardiac AL Amyloidosis: A Report of Two Cases

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Santi Nigrelli ◽  
Giuseppe Curciarello ◽  
Piercarlo Ballo ◽  
Stefano Michelassi ◽  
Francesco Pizzarelli
Keyword(s):  
Cardiac Amyloidosis ◽  
Cardiac Involvement ◽  
Chronic Kidney Disease Stage ◽  
Clinical Results ◽  
Disease Stage ◽  
Comorbid Condition ◽  
Al Amyloidosis ◽  
Therapeutic Approaches ◽  
Hematologic Disease ◽  
Total Remission

Cardiac involvement is a major prognostic determinant in patients with primary AL amyloidosis. The clinical results of standard therapeutic approaches are suboptimal. It has been recently shown that bortezomib, an inhibitor of the proteasome, can induce rapid favourable responses in AL amyloidosis improving cardiac function and survival. Herein we report on two patients with cardiac amyloidosis treated by bortezomib who experienced partial or total remission of hematologic disease and of cardiac involvement. However, death of one patient, suffering from chronic kidney disease stage 5, due to fulminant respiratory syndrome suggests the need for caution in bortezomib use if patients have this comorbid condition.

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