Background: Light chain (AL) and transthyretin (ATTR) cardiac amyloidosis (CA) cause restrictive cardiomyopathy with progressive heart failure. Existing literature highlights a substantial burden of heart failure hospitalizations (HFH) and healthcare utilization among patients with CA, especially in those with delayed diagnosis. Associations between CA HFH and outcomes are not well described, particularly between CA subtypes.
METHODS AND RESULTS: We completed a retrospective cohort study reviewing adults with CA referred to a specialized Cardiac Amyloidosis Clinic between January 2014 and April 2024. We described patterns of hospitalization and associations between HFH and subsequent mortality among CA patients and among AL and ATTR-CM subgroups.
Of 545 patients, amyloid subtype was determined in 429, including 313 (73%) ATTR and 116 (27%) AL. Mean age at diagnosis was 78.0 +/- 11.0 years for ATTR patients and 64.8 +/- 8.9 years for AL, p< 0.001. Majority of patients were male in both subtypes (ATTR 88% vs. 60%, p< 0.001.
At least one HFH occurred in 174 (41%) patients over median follow-up of 2.5 years, including 127 (41%) ATTR and 47 (41%) AL (p=NS). The cumulative duration of all HFH was 22.2+/-26.0 days for ATTR patients compared to 26.6+/-25.7 days for AL patients, p=0.323. A majority of patients with and without HFH were male (79% vs 81%, p=NS). Patients with HFH had lower ejection fraction (50.8% vs 54.0%, p=0.009), lower eGFR (54.9 vs 62.7, p=0.002), and were older (76.3+/-10.7 vs 73.4+/-12.5 years, p=0.01). Median survival from CA diagnosis for patients with and without HFH was 3.17 and 5.98 years respectively, log rank p< 0.0001 (Figure 1). HFH was associated with shorter survival from diagnosis in both subtypes (ATTR 3.07 vs. 5.57 years, log rank p< 0.001; AL 3.67 vs. 9.20 years, log rank p=0.002).
Using Cox proportional hazard models, HFH remained independently associated with survival from diagnosis in the overall cohort (HR 1.84, p=0.0002), ATTR subgroup (HR 2.17, p=0.0006), and AL subgroup (HR 2.20, p=0.036), after adjusting for age, amyloid type, NYHA class, eGFR and BNP/NT-proBNP (AL only), and tafamidis use and NAC disease stage (ATTR only). Among hospitalized patients, median survival from first HFH was 2.16 years for AL patients and 2.71 years for ATTR patients, p=0.76.
Conclusion: Our study shows a 2-fold increase in risk of mortality among CA patients following a HFH, independent of amyloid type. Our findings highlight the importance of early identification and therapy initiation before patients require hospitalization for HF to improve long term outcomes.
