Predictors of poor prognosis in a large cohort of patients with hereditary cardiac transthyretin amyloidosis.

INTRODUCTION AND

OBJECTIVES

Hereditary transthyretin amyloidosis (hATTR) is a rare, multisystemic, autosomal dominant disease. Cardiac involvement worsens prognosis. We aimed to characterize Spanish patients with hATTR cardiac amyloidosis (hATTR-CA) and to identify predictors of poor prognosis.

METHODS

We conducted a retrospective, multicenter study in 39 Spanish hospitals, including adults with genetically confirmed hATTR and cardiac involvement (January 2000-September 2022). Independent predictors of poor prognosis (death, heart transplantation, heart failure, or cardiovascular hospitalization) were identified using multivariate logistic regression. Data were also collected on clinical and genetic characteristics, management patterns, and event-free survival.

RESULTS

A total of 442 patients were included (67.6% male; median age at diagnosis, 65 years). Fifteen TTR variants were identified, with p.Val30Met being the most frequent (64.9%). The most common extracardiac manifestation was neuropathy (64.6%). At baseline, most patients were in New York Heart Association class I-II, with progressive worsening during follow-up. Overall, 48.9% of patients were hospitalized, and 21.9% died; 25.3% of deaths were heart failure-related. Five-year event-free survival was 80.2% from symptom onset and 66.9% from diagnosis. Disease-specific treatments (tafamidis, patisiran, inotersen, or liver transplant) were associated with improved survival (P <.001). In an exploratory analysis stratified by diagnosis before vs after 2018, event-free survival did not differ significantly (HR, 1.04; 95%CI, 0.63-1.72; P=.88). Independent predictors of poor prognosis included New York Heart Association class II-IV, lower left ventricular ejection fraction, elevated N-terminal pro-B-type natriuretic peptide, and the presence of neurological involvement.

CONCLUSIONS

This national cohort-the largest reported to date-highlights the clinical and genetic heterogeneity of hATTR -CA in Spain. Early diagnosis and disease-specific therapies are essential to improving prognosis.