Changing Patterns of Diagnosis and Survival in Transthyretin Cardiac Amyloidosis: A Multicenter Cohort Study.

BACKGROUND: Diagnostic rates of transthyretin cardiac amyloidosis have increased due to growing awareness, noninvasive diagnoses, and treatments that improve morbidity and mortality. We sought to investigate real-world trends in baseline characteristics and survival in the United States. METHODS: Patient-level data at 5 cardiac amyloid referral centers were used, and mortality (defined as death or surgical heart failure therapies) was compared by eras (pre-2010, 2010-2013, 2014-2017, and 2018-2021) and National Amyloidosis Center (NAC) stage. RESULTS: Among 1165 subjects, diagnosis of transthyretin cardiac amyloidosis in a more recent era was associated with older age, white race, wild-type disease, and tafamidis treatment (P<0.001). NAC stage was similar (P=0.866) while Columbia stage was lower (P=0.006) in recent eras, driven by lower New York Heart Association class and loop diuretic dose. Over a median follow-up of 44.5 (interquartile range, 21-60) months, 630 subjects died, and diagnosis in a more recent era was associated with a lower mortality. Tafamidis was protective (hazard ratio [HR], 0.71; P=0.002), and NAC stage >1 portended an increased risk of death (stage 2: HR, 2.00; P<0.001; stage 3: HR, 4.02; P<0.001). There were interactions between tafamidis and both NAC stage and age, suggesting that the beneficial effects of tafamidis were attenuated at higher NAC stages (stage 2: P=0.041; stage 3: P=0.012) and older age (P=0.001). CONCLUSIONS: In this multicenter study of patients seen at referral centers for transthyretin cardiac amyloidosis, diagnosis in a more recent era was associated with improved survival, while tafamidis benefits were attenuated by disease severity and older age. Significant residual mortality risk remains in treated patients at higher disease stages.