Oliver C Cohen 1 Andreia Ismail 1 Babita Pawarova 1 Richa Manwani 1 Sriram Ravichandran 1 Steven Law 1 Darren Foard 1 Sevda Ward 1 Liza Chacko 1 Brooke Douglas ID: 935858
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Slide1
The Impact of Longitudinal Strain on Haematological and Cardiac Response and Survival in Patients with Systemic AL Amyloidosis
Oliver C Cohen1, Andreia Ismail1,Babita Pawarova1, Richa Manwani1, Sriram Ravichandran1, Steven Law1, Darren Foard1, Sevda Ward1, Liza Chacko1, Brooke Douglas1, Ana Martinez-Naharro1, Candida Cristina Quarta2, Shameem Mahmood1, Sajitha Sachchithanantham1, Helen J. Lachmann1, Philip N. Hawkins1 Julian D. Gillmore1, Marianna Fontana1, Rodney H Falk3, Carol J. Whelan1 and Ashutosh D. Wechalekar11National Amyloidosis Centre, University College London, London, United Kingdom.2Alexion Pharmaceuticals Inc., Uxbridge, UK. 3Brigham and Women’s Hospital, 75 Francis Street, Boston, MA, USA
Slide2AL amyloidosis is the commonest subtype [1]
Cardiac involvement is the key determinant of prognosis [2]Impairment of 2-D longitudinal strain is a hallmark of amyloidosis and may provide incremental information above traditional biomarkers [3]Introduction
Slide3All patients from a prospective observational study of newly diagnosed AL amyloidosis (ALCHEMY) were included
Comprehensive assessments inclusive of clonal markers and markers of organ function as well as echocardiography Methods
Slide4Cardiac involvement was defined by a left ventricular wall thickness >12mm on echocardiography as per international consensus criteria or characteristic features of amyloidosis based on MRI.
Patients with cardiac AL amyloidosis had significantly worse strain that those without cardiac involvement Cardiac: -12.2% (Range:-27% - -3.4%) No cardiac: -18.4% (Range:-30.1% - -7.8%)P<0.0001Longitudinal Strain % is worse in patients with cardiac involvement
Slide5Baseline strain is prognostic and independent of Mayo stage
VariableHazard ratio95% CIP valueII
IIIaIIIbGLS ≤-16.2%GLS -12.2 - -16.1%GLS -9.1 - -12.1%GLS ≥-9.0%
Reference1.782.82Reference1.481.68
2.54
1.34-2.38
2.02-3.92
1.05-2.09
1.20-2.36
1.82-3.54
<0.0001
0.024
0.003
<0.0001
<0.0001
<0.0001
<0.0001
Slide6At 6 months: No improvement in CR, LS% worsens if no response (p=0.0005)
At 12 months: LS% improvement in CR only (p=0.04) but worsens if no response (p=0.006)At 24 months: 1/3 of patients in a persistent CR achieve a 2.0% improvement in LS% Change is strain is prognostic and dependent upon haematological response nBaselineLS%
12 months LS %Absolute Change in LS%P value
dFLC<10132
-13.8
(5.03)
-14.6
(5.32)
-0.8
0.01
dFLC 10-40
105
-14.0
(4.44)
-13.4
(4.65)
+0.5
0.13
CR + dFLC<10
72
-13.8
(4.90)
-14.9
(5.31)
-1.1
0.02
Not-CR +
dFLC<1060-13.9(5.21)-14.3(5.36)-0.40.32
Slide7What level of LS% improvement is clinically meaningful?
Slide8Mean difference in calculated LS% was 0.12% (95% CI 0.16% - 1.32%) ad 0.18% (95% CI -2.18% - +1.82%) for intra and inter-observer variability respectively.
Intra- and Inter-observer variability
Slide9Longitudinal strain % improvement is prognostic and provides incremental information over traditional cardiac response
Slide10Longitudinal strain % is prognostic at baseline and following amyloid-directed treatment Longitudinal strain improves in patients in a deep haematological response (CR +
dFLC <10mg/L)Longitudinal strain % provides incremental information over traditional biomarker-based cardiac organ response Conclusions
Slide11We thank Caelum Biosciences for support with data collection costs for this study
The authors have no other competing financial interestsReferences1. Wechalekar AD, Gillmore JD, Hawkins PN. Systemic amyloidosis. Lancet. 2016;387(10038):2641-54.2.Muchtar E, Gertz MA, Kumar SK, Lacy MQ, Dingli D, Buadi FK, et al. Improved outcomes for newly diagnosed AL amyloidosis between 2000 and 2014: cracking the glass ceiling of early death. Blood. 2017;129(15):2111-9.3..Salinaro F, Meier- Ewert HK, Miller EJ, Pandey S, Sanchorawala V, Berk JL, et al. Longitudinal systolic strain, cardiac function improvement, and survival following treatment of light-chain (AL) cardiac amyloidosis. Eur Heart J Cardiovasc Imaging. 2017;18(9):1057-64.Disclosures