Heart Failure Due to Age-Related Cardiac Amyloid Disease Associated With Wild-Type Transthyretin: A Prospective, Observational Cohort Study
Background—Heart failure due to wild-type transthyretin amyloidosis (ATTRwt) is an under-appreciated cause of morbidity and mortality in the aging population. The aims of this study were to examine features of disease and characterize outcomes in a large ATTRwt cohort.
Methods and Results—Over 20 years, 121 patients with ATTRwt were enrolled in a prospective observational study. Median age at enrollment was 75.6 years (range, 62.6-87.8); 97% of patients were Caucasian. The median survival, measured from biopsy diagnosis, was 46.69 months (95% CI, 41.95-56.77); 78% of deaths were due to cardiac causes. By Kaplan-Meier analysis, 5-year survival was 35.7% (95% CI, 25-46). Impaired functional capacity (mean VO2 max of 13.5 mL/kg/min) and atrial fibrillation (67%) were common clinical features. Multivariate predictors of reduced survival were elevated serum brain natriuretic peptide (BNP, 482 ± 337 pg/mL) and uric acid (8.2 ± 2.6 mg/dL), decreased left ventricular ejection fraction (LVEF, 50% median ranging 10-70%), and increased relative wall thickness (RWT, 0.75 ± 0.19).
Conclusions—In this series of patients with biopsy-proven ATTRwt amyloidosis, poor functional capacity and atrial arrhythmias were common clinical features. Elevated BNP and uric acid, decreased LVEF, and increased RWT were associated with limited survival of only 35.7% at 5 years for the group as a whole. These data establish the natural history of ATTRwt, provide statistical basis for the design of future interventional clinical trials, and highlight the need for more sensitive diagnostic tests and disease-specific treatments for this disease.
- Received August 4, 2015.
- Revision received October 27, 2015.
- Accepted November 9, 2015.