Cardiovascular events and interventions in patients with light chain amyloidosis: a real-world study in the United States

Light chain amyloidosis (AL amyloidosis) is a rare disease characterized by the deposition of misfolded immunoglobulin light chains, often in the heart, and is associated with increased risk of cardiovascular (CV) events. We evaluated the incidence of CV events and interventions among US patients with AL amyloidosis. A retrospective analysis was conducted using data from the Optum® de-identified Electronic Health Record (EHR) dataset (~ 106 million patients). Adults with AL amyloidosis were identified by ≥ 2 ICD-10-CM codes (E85.81) or positive mentions in the physician notes (≥ 30 days apart). Patients with ≥ 12 months of pre-index clinical data (index = first diagnosis between January 01, 2017 – March 31, 2021) were included. Cases with transthyretin amyloidosis were excluded unless AL-specific treatment was not evident. CV events (e.g. heart failure) and interventions (e.g. pacemaker) were captured from index to death or study end (March 31, 2022). Incidence and patient‑level event rates were calculated by overall and by stage of cardiac involvement(the European modification of 2004 Mayo staging systems were used for this purpose). A total of 1,859 patients (mean age 66.9 years, 53.9% male) were included in the study. Over a mean follow-up duration of 2.1 years, 64.6% of patients experienced at least one coded CV diagnosis and 16.7% underwent at least one CV intervention during follow-up. Incidence rates (IR) per 100,000 person-years (PY) were 22,068 for CV events and 6,278 for CV interventions. Patient‑level event rates were 61,801 per 100,000 PY for CV events and 8,962 per 100,000 PY, for CV interventions, respectively. Common coded CV diagnoses included conduction disorder and arrhythmias (28,334), heart failure (23,869), and cardiomyopathy (18,833). Most frequent interventions were pacemaker implantation (2,867), cardiac defibrillator implantation (2,349), and angioplasty/bypass (739). The incidence of heart transplant was 228 events per 100,000 PY. The cumulative incidence of CV events increased with disease stage: 38.3% (stage I), 70.3% (II), 81.8% (IIIa), and 89.6% (IIIb) at 30 months (all p < 0.001 vs stage I). The CV intervention cumulative incidence in stage IIIa reached 31.3% at 36 months. Similar findings were observed for stage IIIb. Despite therapeutic advances, patients with AL amyloidosis experience a substantial burden of coded CV diagnoses and interventions in real‑world clinical practice, particularly among those with advanced disease stage. Increased clinician recognition of this rare disease, enabling earlier diagnosis and timely initiation of appropriate therapy, together with an improved understanding of CV progression, is essential to guide management and reduce morbidity.