Heart Failure due to Age-Related Wild-Type Transthyretin Amyloid

Study Questions:

What are the features of heart failure, and what are the outcomes in a large wild-type transthyretin amyloidosis (ATTRwt) cohort?


The study cohort was comprised of 121 patients with ATTRwt enrolled in a prospective observational study over a 20-year period. The investigators used Kaplan-Meier analysis to evaluate the survival curve, and standard statistical methods including Cox proportional hazard regression model were used to analyze the data over a 5-year follow-up period.


The study investigators found that median age at enrollment was 75.6 years (range, 62.6–87.8) and 97% of patients were Caucasian. Presentation commonly featured dyspnea on exertion (86%), peripheral edema (64%), and atrial fibrillation (67%) with onset of symptoms ranging from 59-87.5 years of age. The prevalence of atrial fibrillation was higher than the age-adjusted frequency reported in the general population. The median survival, measured from biopsy diagnosis, was 46.69 months (95% confidence interval [CI], 41.95-56.77), and 78% of the mortality was due to cardiac causes. Five-year survival was 35.7% (95% CI, 25-46). Impaired functional capacity (mean VO2 max of 13.5 ml/kg/min) was a common clinical feature. Multivariate predictors of reduced survival were elevated serum B-type natriuretic peptide (482 ± 337 pg/ml) and uric acid (8.2 ± 2.6 mg/dl), decreased left ventricular ejection fraction (50% median ranging 10-70%), and increased relative wall thickness (0.75 ± 0.19).


The authors concluded that these data establish the natural history of ATTRwt, provide a 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.


This is an important study because it characterizes the natural history of ATTRwt amyloid disease. Given that 78% of the mortality is due to cardiovascular causes suggests that the quest for a cure is urgent. Hopefully, novel therapies such as tafamidis and diflunisal will slow the progression of this disease.

Clinical Topics: Arrhythmias and Clinical EP, Geriatric Cardiology, Heart Failure and Cardiomyopathies, Implantable Devices, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias, Acute Heart Failure, Heart Failure and Cardiac Biomarkers

Keywords: Amyloid Neuropathies, Familial, Amyloidosis, Arrhythmias, Cardiac, Atrial Fibrillation, Diflunisal, Dyspnea, Edema, Geriatrics, Heart Failure, Natriuretic Peptide, Brain, Stroke Volume, Uric Acid

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