Cardiac Biomarker Complete Response in AL Amyloidosis: Characteristics, Cardiac Recovery, and Survival of 63 Patients

Cardiac biomarker complete response (CR) is a new concept in amyloid light chain (AL) cardiac amyloidosis (CA).

The aim of this study was to characterize patients with AL CA who achieved cardiac biomarker CR, including clinical presentation, treatment, cardiac recovery, and survival.

This single-center retrospective cohort study included patients diagnosed with AL CA between 2004 and 2023 who met cardiac biomarker response eligibility (baseline N-terminal pro-B-type natriuretic peptide [NT-proBNP] >650 pg/mL or B-type natriuretic peptide >150 pg/mL). Among these, patients who achieved cardiac biomarker CR, defined as NT-proBNP ≤350 pg/mL or B-type natriuretic peptide ≤80 pg/mL sustained for at least 12 months, were identified. The median follow-up duration was 9.5 years.

Sixty-three patients achieved cardiac biomarker CR (4.7% of evaluable cases [63 of 1,342]). This proportion increased in the second period compared with the first (6.4% [38 of 591] vs 3.3% [25 of 751]; P < 0.001). The median age was 57 years (Q1-Q3: 49-66 years), and 63.5% were men. The median baseline difference between involved and uninvolved free light chains was 429 mg/L (Q1-Q3: 143-708 mg/L), the median pretreatment NT-proBNP concentration was 1,977 pg/mL, and 57.1% of patients were in cardiac stage II. Hematologic CR preceded cardiac biomarker CR in 76% of patients. The median time to cardiac biomarker CR was 20.6 months. At cardiac biomarker CR, the median NT-proBNP concentration was 265 pg/mL (86.9% reduction from baseline). Echocardiographic parameters improved by the time of cardiac biomarker CR but did not fully normalize in all patients. Cardiac progression occurred in 14% of patients, and 44.4% required subsequent clone-directed therapy. Eight patients died, 2 of non-AL CA-related causes. Survival was comparable with that of a matched general U.S. population (P = 0.35).

Cardiac biomarker CR represents the deepest level of cardiac biochemical recovery in AL amyloidosis and is associated with survival similar to the general population. Despite biochemical recovery, structural cardiac abnormalities may persist, underscoring the importance of early diagnosis and timely therapy.