Natural history, hospitalizations and mortality causes in ATTRv V30M amyloidosis in an endemic European cohort

Variant transthyretin amyloidosis (A-ATTRv) caused by the p.Val50Met mutation is a multisystemic disease with marked geographic variability. Mallorca represents one of the main endemic foci in Europe. Although disease-modifying therapies have improved prognosis, real-world data on hospitalization patterns and causes of death remain limited. We conducted a retrospective observational study including deceased patients with A-ATTRv V30M from Mallorca up to November 2024. Demographic characteristics, comorbidity burden, neurological stage, hospital admissions and causes of death were analyzed using clinical records. Fifty-five patients (60% male) were included, with a median age at diagnosis of 68.5 years (IQR 59–75). Most patients (78.2%) presented a mixed neurological and cardiac phenotype. During follow-up, 41.8% experienced five or more emergency department visits or hospital admissions. Infectious complications, particularly urinary tract infections, were the most frequent cause of hospitalization, followed by cardiovascular events, mainly heart failure. Cardiovascular causes accounted for the largest proportion of deaths (29.1%), predominantly heart failure and sudden death. Median overall from diagnosis to death was 70 months (IQR 37–108). In this endemic A-ATTRv V30M cohort, cardiovascular complications—especially heart failure—were the main causes of mortality and a major driver of hospitalization, highlighting the importance of early multidisciplinary management.