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JOURNAL ARTICLE
OBSERVATIONAL STUDY
RESEARCH SUPPORT, N.I.H., EXTRAMURAL
RESEARCH SUPPORT, NON-U.S. GOV'T
Heart Failure Resulting From Age-Related Cardiac Amyloid Disease Associated With Wild-Type Transthyretin: A Prospective, Observational Cohort Study.
Circulation 2016 January 20
BACKGROUND: Heart failure caused by wild-type transthyretin amyloidosis (ATTRwt) is an underappreciated cause of morbidity and mortality in the aging population. The aims of this study were to examine features of disease and to 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 years); 97% of patients were white. The median survival, measured from biopsy diagnosis, was 46.69 months (95% confidence interval, 41.95-56.77); 78% of deaths were attributable to cardiac causes. By Kaplan-Meier analysis, 5-year survival was 35.7% (95% confidence interval, 25-46). Impaired functional capacity (mean Vo2max, 13.5 mL·kg(-1)·min(-1)) and atrial fibrillation (67%) were common clinical features. Multivariate predictors of reduced survival were elevated serum brain natriuretic peptide (482 ± 337 pg/mL) and uric acid (8.2 ± 2.6 mg/dL), decreased left ventricular ejection fraction (50% median; range, 10%-70%), and increased relative wall thickness (0.75 ± 0.19).
CONCLUSIONS: In this series of patients with biopsy-proven ATTRwt, poor functional capacity and atrial arrhythmias were common clinical features. Elevated brain natriuretic peptide and uric acid, decreased left ventricular ejection fraction, and increased relative wall thickness 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.
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 years); 97% of patients were white. The median survival, measured from biopsy diagnosis, was 46.69 months (95% confidence interval, 41.95-56.77); 78% of deaths were attributable to cardiac causes. By Kaplan-Meier analysis, 5-year survival was 35.7% (95% confidence interval, 25-46). Impaired functional capacity (mean Vo2max, 13.5 mL·kg(-1)·min(-1)) and atrial fibrillation (67%) were common clinical features. Multivariate predictors of reduced survival were elevated serum brain natriuretic peptide (482 ± 337 pg/mL) and uric acid (8.2 ± 2.6 mg/dL), decreased left ventricular ejection fraction (50% median; range, 10%-70%), and increased relative wall thickness (0.75 ± 0.19).
CONCLUSIONS: In this series of patients with biopsy-proven ATTRwt, poor functional capacity and atrial arrhythmias were common clinical features. Elevated brain natriuretic peptide and uric acid, decreased left ventricular ejection fraction, and increased relative wall thickness 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.
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