Multiparametric Mapping
Adam Ioannou, MBBS BSc
Doctor
National Amyloidosis Center, United Kingdom
Adam Ioannou, MBBS BSc
Doctor
National Amyloidosis Center, United Kingdom
Rishi Patel, MD
Senior Clinical Fellow and PhD Student
Royal Free London NHS Foundation Trust, United Kingdom
Yousuf Razvi, MD, BSc
Doctor
National Amyloidosis Center, United Kingdom
Aldostefano Porcari, MD
Doctor
National Amyloidosis Center, United Kingdom
Ana Martinez Naharro, MD, PhD
Doctor
National Amyloidosis Center, United Kingdom
David Hutt
Doctor
National Amyloidosis Center, United Kingdom
Lucia Venneri
Doctor
National Amyloidosis Center, United Kingdom
Helen J. Lachmann, MD
Doctor
National Amyloidosis Center, England, United Kingdom
Carol Whelan, MD
Doctor
National Amyloidosis Center, England, United Kingdom
Philip D. Hawkins, MD, PhD
Doctor
National Amyloidosis Center
London, England, United Kingdom
Julian D. Gillmore, MD, PhD
Doctor
National Amyloidosis Center, England, United Kingdom
Ashutosh Wechalekar, MD, PhD
Doctor
National Amyloidosis Center, United Kingdom
Marianna Fontana, MD, PhD
Consultant Cardiologist, Director UCL CMR unit at the RFH
University College London
London, England, United Kingdom
Systemic light-chain (AL) amyloidosis commonly involves the heart, liver, and spleen. Cardiac magnetic resonance (CMR) with extracellular volume (ECV) mapping has demonstrated accuracy in measuring cardiac, hepatic and splenic amyloid infiltration. We sought to: (1) assess the association between baseline multi-organ ECVs and prognosis (2) assess the multi-organ response to treatment using ECV mapping, and (3) assess the association between multi-organ treatment response and prognosis.
Methods:
We identified 351 patients with a confirmed diagnosis of systemic AL amyloidosis who underwent baseline serum amyloid P component (SAP) scintigraphy and CMR at diagnosis, of which 171 had follow-up imaging. We also recruited 20 healthy volunteers who underwent CMR with ECV mapping, without corresponding SAP scintigraphy, to allow calculation of the ECV normal ranges.
Results:
At diagnosis, ECV mapping demonstrated that 304(86.7%) had cardiac involvement, 114(32.5%) significant hepatic involvement and 147(41.9%) significant splenic involvement. Baseline myocardial and liver ECV independently predict mortality (myocardial: HR=1.05,95CI%[1.03-1.07],P< 0.001; liver: HR=1.03,95%CI[1.01-1.05],P< 0.001). Liver and spleen ECV correlated with amyloid load assessed by SAP scintigraphy (R=0.751,P< 0.001; R=0.765,P< 0.001, respectively). Serial multi-organ ECV measurements accurately tracked treatment response as validated against serial SAP scintigraphy (the current reference standard). Multi-organ ECV regression was observed as early as 6-months in patients with a good haematological response (liver=15%, spleen=15%, heart=5%). The remaining patients with a good haematological response had stable liver and spleen ECVs, but 20% had cardiac progression. By 12-months more patients with a good haematological response demonstrated cardiac regression (liver=30%, spleen=36%, heart=32%), and this trend was maintained at 24-months. Multi-variable analysis adjusting for haematological response, change in myocardial, liver and spleen ECV demonstrated that haematological response, change in myocardial ECV (HR=1.11, 95%CI[1.02-1.19], P=0.011) and liver ECV (HR=1.06, 95%CI[1.01-1.11], P=0.015) remained independent predictors of prognosis at 6-months.
Conclusion:
Multi-organ ECV quantification accurately tracks treatment response, and demonstrates different rates of organ regression, with the liver and spleen regressing more rapidly than the heart. A good haematological response alone is likely to induce visceral organ stabilisation/regression, but may not be sufficient to induce myocardial stabilisation/regression. Liver and myocardial ECV at diagnosis and changes in ECV at 6-months independently predict mortality. ECV mapping offers a comprehensive multi-organ assessment of treatment response and accurate prognostication.