Myocardial Composition Differences Between Patients with Active Disease versus Those in Remission for Cardiac Light Chain Amyloidosis

Disease-modifying therapies for light chain (AL) amyloidosis target the plasma cells that produce excess immunoglobulin AL. However, amyloid infiltration remains in tissues even after production of new amyloid is successfully prevented. Although patients with AL cardiac amyloidosis (AL-CA) feel better when in remission, they are still at a higher risk for cardiac disease.

Changes in the composition of the myocardial interstitium after remission for AL-CA have not been well-characterized. In a new study, researchers tested their hypothesis that patients in remission for AL-CA would have different interstitial composition compared with patients with active amyloidosis.

Patients with AL-CA confirmed by biopsy and cardiac involvement were enrolled in the prospective, cross-sectional cohort study. The active disease group included 48 patients with increased serum-free ALs and abnormal kappa–lambda ratios or elevated numbers of bone marrow clonal plasma cells. Eleven of these patients had started chemotherapy but still had elevated serum-free ALs. The remission group included 21 patients treated for plasma-cell dyscrasia with differential-free AL levels <40 mg/L or a normal serum-free AL ratio for ≥1 years. Consistent with successful therapy, New York Heart Association functional classes and mean 6-minute walk distance were better in the remission group than in the active group.

All patients underwent contrast-enhanced cardiac magnetic resonance imaging to assess myocardial extracellular volume and composition. The researchers found that total amyloid burden, myocardial fibrosis, and cardiomyocyte volume were similar between remission and active disease groups. Extracellular volume in both groups was higher than in the normal reference range but not significantly different between groups.

In contrast, T11 and T2 values differed between groups. Patients in the remission group had higher native T1 relaxation time compared with patients in the active group (P = .024), suggesting differences in myocardial composition. T2 values were also significantly higher in the remission group compared with the active group (P = .008), although the values in the remission group were still in the normal range. T2 values are thought to indicate water content, so the researchers concluded that their results suggested that AL-CA does not typically cause edema. These results contrast with a previous study that found elevated myocardial T2 relaxation times in patients with AL-CA.

The researchers also noted that native T1 relaxation time and T2 values were negatively correlated with serum differential-free AL levels. They suggested that these correlations might reflect changes in fibril formation and fibrosis during disease progression and treatment and indicate lower interstitial amyloid levels.

Limitations of the study are the cross-sectional design, small size, lack of serial longitudinal measurements, and potential for survival bias given the high mortality of AL-CA during the first year after diagnosis.

The researchers suggested that their results are consistent with lower levels of amyloid in the myocardial interstitium after achieving remission. They proposed that future studies are needed to better characterize the composition of the interstitium.

Source: Cuddy SAM, Jerosch-Herold M, Falk RH, et al. Myocardial composition in light-chain cardiac amyloidosis more than 1 year after successful therapy. JACC Cardiovasc Imaging. 2022;15:594-603.

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