Cardiovascular magnetic resonance in light-chain amyloidosis to guide treatment

Abstract

Aims: To assess the ability of cardiovascular magnetic resonance (CMR) to (i) measure changes in response to chemotherapy; (ii) assess the correlation between haematological response and changes in extracellular volume (ECV); and (iii) assess the association between changes in ECV and prognosis over and above existing predictors.

Methods and results: In total, 176 patients with cardiac AL amyloidosis were assessed using serial N-terminal pro-B-type natriuretic peptide (NT-proBNP), echocardiography, free light chains and CMR with T1 and ECV mapping at diagnosis and subsequently 6, 12, and 24 months after starting chemotherapy. Haematological response was graded as complete response (CR), very good partial response (VGPR), partial response (PR), or no response (NR). CMR response was graded by changes in ECV as progression (≥0.05 increase), stable (<0.05 change), or regression (≥0.05 decrease). At 6 months, CMR regression was observed in 3% (all CR/VGPR) and CMR progression in 32% (61% in PR/NR; 39% CR/VGPR). After 1 year, 22% had regression (all CR/VGPR), and 22% had progression (63% in PR/NR; 37% CR/VGPR). At 2 years, 38% had regression (all CR/VGPR), and 14% had progression (80% in PR/NR; 20% CR/VGPR). Thirty-six (25%) patients died during follow-up (40 ± 15 months); CMR response at 6 months predicted death (progression hazard ratio 3.82; 95% confidence interval 1.95-7.49; P < 0.001) and remained prognostic after adjusting for haematological response, NT-proBNP and longitudinal strain (P < 0.01).

Conclusions: Cardiac amyloid deposits frequently regress following chemotherapy, but only in patients who achieve CR or VGPR. Changes in ECV predict outcome after adjusting for known predictors.

Keywords: Amyloidosis; CMR; ECV; T1 mapping.

Structured Graphical Abstract

ECV, extracellular volume; EDV, end-diastolic volume; LV, left ventricle; LVEF, LV ejection fraction; MAPSE, mitral annular plane systolic excursion; TAPSE, tricuspid annular plane systolic excursion.

Figure 1

Cardiac systemic light-chain amyloid regression on serial cardiovascular magnetic resonance scans at baseline (top row) and after treatment with chemotherapy at 6 months (second row) and 1 year (third row). Reductions in native T1, late gadolinium enhancement, and extracellular volume within the myocardium are demonstrated progressively over the course of treatment.

Figure 2

Cardiac systemic light-chain amyloid progression on serial cardiovascular magnetic resonance scans at baseline (top row) and after treatment with chemotherapy at 6 months (second row). Increase in native T1, late gadolinium enhancement, and extracellular volume within the myocardium are demonstrated after not achieving good response to chemotherapy at 6 months.

Figure 3

Bar chart with 95% confidence intervals, representing the proportion of patients with each grade of cardiovascular magnetic resonance response to chemotherapy at each time points studied (6 months, 1 year, and 2 years). Amyloid progression defined as ≥5% increase in extracellular volume, stable amyloid load defined as <5% change in extracellular volume and amyloid regression defined as ≥5% decrease in extracellular volume.

Figure 4

Dot plots comparing changes of extracellular volume from baseline to 6 months, 1 year after chemotherapy (solid horizontal lines represent group medians).

Figure 5

Kaplan–Meier survival curves, with shaded 95% confidence regions, displaying survival in all patients according to change in amyloid burden (measured by the change in extracellular volume on follow-up cardiovascular magnetic resonance) after 6 months (left panel) and 1 year of chemotherapy (right panel).