Progression, regression and redefining the treatment response – cardiac magnetic resonance with T1 and extracellular volume mapping in cardiac light-chain amyloidosis
Authors: Patel R , Martinez-Naharro A , Kotecha T , Karia N , Ioannou A , Petrie A , Chacko L , Razvi Y , Lachmann H , Venneri L , Kellman P , Gillmore J , Hawkins P , Wechalekar A , Fontana M 
Published: October 2022

Abstract

Background
The presence and severity of cardiac involvement in AL amyloidosis is the main driver of prognosis [1]; patients with symptomatic heart failure frequently die within 6 months [1] but median survival has nearly doubled over the past decade, mainly due to significant improvements in chemotherapy. The haematological response to chemotherapy is principally evaluated with serial measurements of serum-free light-chains (FLC) [2]. The cardiac response to chemotherapy is assessed through changes in serum concentrations of brain natriuretic peptides (including NT-proBNP) and echocardiographic parameters [3–5]. Neither are able to directly measure cardiac amyloid burden. Cardiovascular magnetic resonance (CMR) with extra-cellular volume (ECV) mapping can measure the extent cardiac amyloid infiltration [6].

Aims
We investigated the ability of CMR to: 1) measure changes in response to chemotherapy; 2) assess the correlation between haematological response (HMR) and changes in cardiac amyloid; 3) assess the association between changes in cardiac amyloid and prognosis over and above existing predictors.

Methods
In total, 176 patients with cardiac light-chain amyloidosis treated with chemotherapy were assessed with FLC, NT-proBNP and CMR with ECV mapping at baseline (before chemotherapy), 6-months, 12-months & 24-months after commencing chemotherapy. Haematological response was categorized by reductions in FLC as: complete response (CR), very good partial response (VGPR), partial response (PR) or no response (NR). CMR response was categorized by changes in ECV as: progression (≥0.05 increase), stable (&lt;0.05 change) or regression (≥0.05 decrease).

Results
A progressive increase in patients achieving either CR or VGPR was observed at each time point (61% of patients at 6-months, 71% at 12-months and 80% at 24-months). At 6-months, CMR regression was observed in 3% (all had either CR or VGPR) and progression in 32% (61% had either PR or NR; 39% had either CR or VGPR). At 1-year, CMR regression was observed in 22% (all had either CR or VGPR); progression in 22% (63% had either PR or NR; 37% had either CR or VGPR). At 2-years, CMR regression was observed in 38% (all had CR/VGPR); progression in 14% (80% had either PR or NR; 20% had either CR or VGPR). During follow-up (40±15 months), 36 (25%) patients died. CMR response at 6-months predicted death (progression HR 3.821; 95% CI 1.950–7.487; p&lt;0.001) and remained independently associated with prognosis after adjusting for haematological response, NT-proBNP and longitudinal strain on echocardiography (p&lt;0.01).

Conclusions
CMR demonstrates that cardiac amyloid deposits frequently regress following chemotherapy, but only in patients who achieve CR or VGPR, highlighting the need for deep haematological response. Changes in amyloid burden (ECV) predict outcomes after adjusting for known predictors, showing the crucial role of CMR in redefining treatment response.

Funding Acknowledgement
Type of funding sources: Foundation.