Clinical Outcomes and Prognosis

1355817 - Extracellular Volume Mapping by Cardiac Magnetic Resonance to Guide Treatment in Systemic Immunoglobulin Light Chain Amyloidosis: sub-analysis from the ALCHEMY study

Friday, January 27, 2023

9:30 AM – 9:40 AM

Location: Silver Pearl 2

Presenting Author(s)

AP

Aldostefano Porcari, MD

Doctor
National Amyloidosis Center, United Kingdom

Primary Author(s)

AP

Aldostefano Porcari, MD

Doctor
National Amyloidosis Center, United Kingdom

Co-Author(s)

AM

Ambra Masi, MD

Senior Clinical Fellow and PhD Student
Royal Free London NHS Foundation Trust, United Kingdom
YR

Yousuf Razvi, MD, BSc

Doctor
National Amyloidosis Center, United Kingdom
RP

Rishi Patel, MD

Senior Clinical Fellow and PhD Student
Royal Free London NHS Foundation Trust, United Kingdom
AI

Adam Ioannou, MBBS BSc

Doctor
National Amyloidosis Center, United Kingdom
MR

Muhammad U. Rauf, MD

Senior Clinical Fellow and PhD Student
Royal Free London NHS Foundation Trust, United Kingdom
AM

Ana Martinez Naharro, MD, PhD

Doctor
National Amyloidosis Center, United Kingdom
Tushar Kotecha, MD, PhD

Doctor
National Amyloidosis Center
London, England, United Kingdom
Dan Knight, BSc(Hons) MBBS MRCP MD(Res)

Consultant Cardiologist
Royal Free London NHS Foundation Trust
LV

Lucia Venneri

Doctor
National Amyloidosis Center, United Kingdom
AW

Ashutosh Wechalekar, MD, PhD

Doctor
National Amyloidosis Center, United Kingdom
PH

Philip D. Hawkins, MD, PhD

Doctor
National Amyloidosis Center
London, England, United Kingdom
JG

Julian D. Gillmore, MD, PhD

Doctor
National Amyloidosis Center, England, United Kingdom
Marianna Fontana, MD, PhD

Consultant Cardiologist, Director UCL CMR unit at the RFH
University College London
London, England, United Kingdom

Disclosure(s):

Dan Knight, BSc(Hons) MBBS MRCP MD(Res): No financial relationships to disclose

Marianna Fontana, MD, PhD: No relevant disclosure to display

Background:

Achieving a rapid and profound suppression of the amyloidogenic light chain in patients with systemic immunoglobulin light chain amyloidosis (AL amyloidosis) is currently the goal of treatment in all patients¹. However, achieving a rapid and profound haematological response with aggressive chemotherapy regimens is often associated with significant morbidity and mortality. We propose that cardiac magnetic resonance (CMR) with extracellular volume (ECV) mapping can subclassify patients with systemic AL amyloidosis and better guide treatment strategies at an individual level². The aim of this study was to assess the ability of ECV mapping to stratify prognosis in the different sub-classes of haematological response to chemotherapy treatment and the associated implications for patients management.

Methods: Study subjects comprised individuals with systemic AL amyloidosis involvement identified from a long-term prospective observational study of newly diagnosed AL amyloidosis patients (ALchemy) conducted at the National Amyloidosis Centre (NAC), United Kingdom. Patients with contraindications for CMR (due to renal impairment, pacemaker implantation, or difficulties to lie flat) were not included in this study. All included patients underwent comprehensive clinical, laboratory and instrumental work up, including CMR imaging with evaluation of left ventricular (LV) mass, late gadolinium enhancement (LGE) and ECV mapping. Haematological response at 1 and 12 months was defined according to guidelines. The main outcome was all-cause mortality.

Results: The study population included 508 untreated AL patients: median age 68 (interquartile range [IQR] 61-75) years, 61.5% male, median NT-proBNP 2353 ng/L (IRQ 531-7192), median LVEF 66% [IQR 57-73]. Haematological response at 1 month was as following: 42.7% (n=217) no response, 29.3% (n=149) partial response, 16.5% (n=84) very good partial response (VGPR) and 11.4% (n=58) complete response (CR). ECV was able to measure the continuum of cardiac amyloid infiltration, from no deposit (ECV < 0.30), to early (ECV 0.31-0.40), to moderate (ECV 0.41-0.50), moderate to severe (ECV 0.51-0.60) and severe infiltration (ECV >0.60). During a median follow up of 33 (IQR 7-54) months, ECV was independently associated with all-cause mortality, with each category of infiltration conferring an incremental risk (p< 0.001,Figure). Regardless of the rapidity and degree of the haematological response, patients with no cardiac infiltration (ECV < 0.30) showed excellent long-term survival whilst in the different classes of cardiac infiltration there was a progressively higher impact of haematological response on mortality, with more favourable outcome observed in patients achieving VGPR and/or CR at 1 month and at 12 months (Figure).

Conclusion: ECV mapping provided independent and incremental prognostic stratification in AL amyloidosis over rapidity and degree of haematological response, potentially serving as novel tool to guide treatment strategies.