ECV mapping, in systemic AL amyloidosis an independent predictor of prognosis: JAMA
UK: In a recent study published in JAMA Cardiology, researchers have unveiled new insights into managing systemic immunoglobulin AL amyloidosis, particularly emphasizing the role of extracellular volume (ECV) mapping as a crucial tool for predicting patient outcomes. This revelation marks a significant shift in how clinicians approach treatment for this rare but severe condition characterized by the deposition of amyloid proteins in organs, most critically the heart.
The researchers revealed that ECV mapping reshapes the understanding of hematological responses linked to improved outcomes and holds the promise of guiding more effective treatment strategies. ECV mapping is a technique used to assess the volume of extracellular space in cardiac tissues.
The cohort study encompassed 560 newly diagnosed systemic AL amyloidosis patients who underwent cardiac magnetic resonance (CMR) imaging with ECV mapping before starting chemotherapy. Among various methods for assessing cardiac involvement, ECV mapping emerged as the sole independent prognostic indicator.
"It offered valuable insights into how the depth and speed of hematological response correlate with patient outcomes, highlighting that a swift and substantial hematological response is particularly crucial for those with elevated ECV levels," the researchers wrote.
Systemic light-chain (AL) amyloidosis, a condition resulting from the abnormal accumulation of light-chain amyloid proteins, often leads to severe cardiac complications. Traditionally, treatment strategies have focused primarily on the reduction of amyloid-producing plasma cells and the overall control of disease progression. The key determinant of survival in systemic AL amyloidosis is cardiac amyloid infiltration. Current guidelines advise early therapy modification for patients showing nonoptimal or suboptimal responses, irrespective of the degree of cardiac amyloid infiltration.
Against the above background, Aldostefano Porcari, University College London, Royal Free Hospital, London, United Kingdom, and colleagues aimed to evaluate the differences between serum biomarkers, echocardiography, and CMR with ECV mapping in characterizing cardiac amyloid, the independent prognostic role of these approaches, and the ECV mapping's role to guide treatment strategies.
From 2015 to 2021, consecutive patients newly diagnosed with systemic AL amyloidosis underwent echocardiography, cardiac biomarker assessments, and cardiac magnetic resonance (CMR) imaging with ECV mapping at the time of diagnosis.
The primary outcomes of the study included all-cause mortality and hematological response, categorized into no response (NR), partial response (PR), very good partial response (VGPR), and complete response (CR) based on validated criteria. Secondary outcomes focused on the depth and speed of the hematological response, as well as overall survival with ECV levels.
The following were the key findings of the study:
- Of 560 patients with AL amyloidosis, the median age was 68 years; 61.8% were males.
- Over a median of 40.5 months, ECV was independently associated with mortality.
- In the landmark analysis at one month, long-term survival was independent of the achieved hematological response in ECV less than 0.30% and ECV of 0.31% to 0.40%, while it was dependent on the depth of the hematological response in ECV greater than 0.40%.
- In the landmark analysis at six months, survival was independent of the achieved hematological response in ECV less than 0.30% and dependent on achieving at least PR in ECV of 0.31% to 0.40%.
- Survival was dependent on achieving CR in ECV of 0.41% to 0.50% and ECV greater than 0.50%.
- Achieving a deep hematological response at one month was associated with better survival than six months in patients with ECV greater than 0.40% but not with ECV less than 0.40%.
This study demonstrated that CMR with ECV mapping provides a significant advantage by precisely assessing the presence and extent of cardiac amyloid infiltration, surpassing the accuracy of serum cardiac biomarkers and echocardiography.
"ECV mapping not only independently predicts overall survival in systemic AL amyloidosis but also helps delineate hematological responses that correlate with improved long-term survival based on the degree and severity of cardiac amyloid infiltration," the researchers concluded.
Reference:
Porcari A, Masi A, Martinez-Naharro A, et al. Redefining Cardiac Involvement and Targets of Treatment in Systemic Immunoglobulin AL Amyloidosis. JAMA Cardiol. Published online August 21, 2024. doi:10.1001/jamacardio.2024.2555
