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CARDIAC UPTAKE IN AL AMYLOIDOSIS OF 99MTC-DPD AS A NOVEL MARKER OF POOR PROGNOSIS IN SYSTEMIC AL AMYLOIDOSIS
Author(s): ,
Jiexin Zheng
Affiliations:
Haematology,Royal Free Hospital, London,London,United Kingdom
,
D Hutt
Affiliations:
National Amyloidosis Centre,University College London,London,United Kingdom
,
J Gillmore
Affiliations:
National Amyloidosis Centre,University College London,London,United Kingdom
,
C Whelan
Affiliations:
National Amyloidosis Centre,University College London,London,United Kingdom
,
C Quarta
Affiliations:
National Amyloidosis Centre,University College London,London,United Kingdom
,
M Fontana
Affiliations:
National Amyloidosis Centre,University College London,London,United Kingdom
,
P Hawkins
Affiliations:
National Amyloidosis Centre,University College London,London,United Kingdom
A Wechalekar
Affiliations:
National Amyloidosis Centre,University College London,London,United Kingdom
(Abstract release date: 05/19/16) EHA Library. ZHENG J. 06/12/16; 135311; S817
Dr. Jiexin ZHENG
Dr. Jiexin ZHENG
Contributions
Abstract
Abstract: S817

Type: Oral Presentation

Presentation during EHA21: On Sunday, June 12, 2016 from 09:00 - 09:15

Location: Hall C14

Background
The prognosis and outcomes in systemic AL amyloidosis are determined by cardiac involvement.  The standard method for assessing degree of cardiac impairment in AL amyloidosis has relied on cardiac biomarkers like NT-proBNP and cardiac troponin-T.  However, these markers are not specific for cardiac amyloidosis and other factors like renal failure or fluid overload may affect the levels and limit their utility in determining the prognosis.  Thus far, no imaging modality has accurately predicted outcomes in AL amyloidosis.  In recent years, the role of bone scintigraphy tracers like technetium-99m-labelled 3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) has been evaluated.  They are very sensitive in non-AL amyloidosis.  The utility of 99mTc-DPD scintigraphy in AL amyloidosis has not been studied.

Aims
We report here in a series of 189 patients in which cardiac uptake using 99mTc-DPD scintigraphy is a marker of very poor outcome in AL amyloidosis.

Methods
All patients who underwent 99mTc-DPD scintigraphy with a confirmed diagnosis of AL amyloidosis were identified from the database of the UK National Amyloidosis Centre.  189 patients with systemic AL cardiac amyloidosis had 99mTc-DPD scans at diagnosis from June 2010-November 2015.  All patients also had a full protocolized amyloid assessment including cardiac biomarkers, haematology, biochemistry, echocardiography and SAP scintigraphy.  All patients are followed up every 3-6 months for prospective protocolized follow up.  The characteristics of patients with a positive scan were compared with those patients in whom the scan did not show cardiac uptake.  The survival outcomes were assessed by the method of Kaplan and Meier.  Cox regression was used to determine univariate and multivariate variables impacting survival.

Results
A total of 189 patients were identified.  114 (60%) had no cardiac uptake on 99mTc-DPD scans (DPD-negative) and 75 (40%) had cardiac uptake on 99mTc-DPD scans (DPD-positive); 57 (76%) had grade 1 cardiac uptake, 13 (17%) had grade 2 and 5 (7%) grade 3.  There was no significant difference between the DPD-positives and DPD-negatives in terms of NYHA class I/II versus III/IV (64% and 36% in the DPD-positives vs. 67% and 33% in the DPD-negatives, p = 0.75); Mayo staging 1/2 vs. 3 (17% and 83% vs. 25% and 75%, p = 0.20); supine systolic blood pressure (112 vs. 116, p = 0.26).  The echocardiographic parameters were also similar in the positive and negative groups: LVEF (50% vs. 55%, p = 0.1); mean LV wall (15mm vs. 15mm, p = 0.39); e/e’ (18 vs. 17, p = 0.58).  Organ involvement did not show a significant difference between the DPD-positives and DPD-negatives (renal: 52% vs. 48%, p = 0.66; autonomic nervous system: 20% vs. 14%, p = 0.32).  The serum free light chains showed no significant difference (median dFLC 343mg/L vs. 316mg/L, p = 0.40).  However, the cardiac biomarkers were significantly greater in the DPD-positives compared to the DPD-negatives: N-terminal fragment of brain natriuretic peptide (NT-proBNP) (8296 ng/L vs. 4411 ng/L, p=0.005) and high sensitivity troponin (hsTNT) (113 ug/L vs. 83 ug/L, p=0.001).  The overall median survival of the whole cohort was 7 months (95% CI 3 to 11 months).  In the DPD-positive group the median survival was 4.3 months compared to 11.8 months in those with cardiac involvement by conventional criteria but DPD-negative (p=0.045).  On univariate analysis factors impacting survival were: cardiac involvement, Mayo disease stage, presenting dFLC levels, NT-proBNP, hsTNT and cardiac uptake on 99mTc-DPD scintigraphy.  Multivariate models will be presented. 

Conclusion
99mTc-DPD scintigraphy is a useful imaging modality in cardiac AL amyloidosis showing cardiac uptake in 40% of patients with cardiac involvement by conventional criteria.  Patients with positive scans for cardiac uptake have significantly higher NT-proBNP and hsTNT compared to those with negative scans. Cardiac uptake on 99mTc-DPD scan is associated with very poor outcomes.  We believe that uptake on a 99mTc-DPD scan shows advanced cardiac disease independent of all other markers of cardiac involvement in AL amyloidosis.  These findings suggest that 99mTc-DPD scintigraphy should be considered as a simple baseline prognostic investigation in all patients with cardiac AL amyloidosis.

Session topic: Experimental approaches for plasma cell disorders

Keyword(s): Amyloidosis
Abstract: S817

Type: Oral Presentation

Presentation during EHA21: On Sunday, June 12, 2016 from 09:00 - 09:15

Location: Hall C14

Background
The prognosis and outcomes in systemic AL amyloidosis are determined by cardiac involvement.  The standard method for assessing degree of cardiac impairment in AL amyloidosis has relied on cardiac biomarkers like NT-proBNP and cardiac troponin-T.  However, these markers are not specific for cardiac amyloidosis and other factors like renal failure or fluid overload may affect the levels and limit their utility in determining the prognosis.  Thus far, no imaging modality has accurately predicted outcomes in AL amyloidosis.  In recent years, the role of bone scintigraphy tracers like technetium-99m-labelled 3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) has been evaluated.  They are very sensitive in non-AL amyloidosis.  The utility of 99mTc-DPD scintigraphy in AL amyloidosis has not been studied.

Aims
We report here in a series of 189 patients in which cardiac uptake using 99mTc-DPD scintigraphy is a marker of very poor outcome in AL amyloidosis.

Methods
All patients who underwent 99mTc-DPD scintigraphy with a confirmed diagnosis of AL amyloidosis were identified from the database of the UK National Amyloidosis Centre.  189 patients with systemic AL cardiac amyloidosis had 99mTc-DPD scans at diagnosis from June 2010-November 2015.  All patients also had a full protocolized amyloid assessment including cardiac biomarkers, haematology, biochemistry, echocardiography and SAP scintigraphy.  All patients are followed up every 3-6 months for prospective protocolized follow up.  The characteristics of patients with a positive scan were compared with those patients in whom the scan did not show cardiac uptake.  The survival outcomes were assessed by the method of Kaplan and Meier.  Cox regression was used to determine univariate and multivariate variables impacting survival.

Results
A total of 189 patients were identified.  114 (60%) had no cardiac uptake on 99mTc-DPD scans (DPD-negative) and 75 (40%) had cardiac uptake on 99mTc-DPD scans (DPD-positive); 57 (76%) had grade 1 cardiac uptake, 13 (17%) had grade 2 and 5 (7%) grade 3.  There was no significant difference between the DPD-positives and DPD-negatives in terms of NYHA class I/II versus III/IV (64% and 36% in the DPD-positives vs. 67% and 33% in the DPD-negatives, p = 0.75); Mayo staging 1/2 vs. 3 (17% and 83% vs. 25% and 75%, p = 0.20); supine systolic blood pressure (112 vs. 116, p = 0.26).  The echocardiographic parameters were also similar in the positive and negative groups: LVEF (50% vs. 55%, p = 0.1); mean LV wall (15mm vs. 15mm, p = 0.39); e/e’ (18 vs. 17, p = 0.58).  Organ involvement did not show a significant difference between the DPD-positives and DPD-negatives (renal: 52% vs. 48%, p = 0.66; autonomic nervous system: 20% vs. 14%, p = 0.32).  The serum free light chains showed no significant difference (median dFLC 343mg/L vs. 316mg/L, p = 0.40).  However, the cardiac biomarkers were significantly greater in the DPD-positives compared to the DPD-negatives: N-terminal fragment of brain natriuretic peptide (NT-proBNP) (8296 ng/L vs. 4411 ng/L, p=0.005) and high sensitivity troponin (hsTNT) (113 ug/L vs. 83 ug/L, p=0.001).  The overall median survival of the whole cohort was 7 months (95% CI 3 to 11 months).  In the DPD-positive group the median survival was 4.3 months compared to 11.8 months in those with cardiac involvement by conventional criteria but DPD-negative (p=0.045).  On univariate analysis factors impacting survival were: cardiac involvement, Mayo disease stage, presenting dFLC levels, NT-proBNP, hsTNT and cardiac uptake on 99mTc-DPD scintigraphy.  Multivariate models will be presented. 

Conclusion
99mTc-DPD scintigraphy is a useful imaging modality in cardiac AL amyloidosis showing cardiac uptake in 40% of patients with cardiac involvement by conventional criteria.  Patients with positive scans for cardiac uptake have significantly higher NT-proBNP and hsTNT compared to those with negative scans. Cardiac uptake on 99mTc-DPD scan is associated with very poor outcomes.  We believe that uptake on a 99mTc-DPD scan shows advanced cardiac disease independent of all other markers of cardiac involvement in AL amyloidosis.  These findings suggest that 99mTc-DPD scintigraphy should be considered as a simple baseline prognostic investigation in all patients with cardiac AL amyloidosis.

Session topic: Experimental approaches for plasma cell disorders

Keyword(s): Amyloidosis

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