Natural History of Wild-Type Transthyretin Cardiac Amyloidosis

Study Questions:

What is the natural history of wild-type transthyretin cardiac amyloidosis (ATTRwt) and the predictors of survival?

Methods:

The investigators retrospectively reviewed patients diagnosed with ATTRwt at the Mayo Clinic through 2013, and recorded clinical data and survival. Factors affecting overall survival were identified, and a prognostic staging system was developed. Cox proportional hazards regression was used to test for association of baseline variables with mortality. Results of these models were summarized as hazard ratio (HR) and 95% confidence interval.

Results:

The median age of the 360 patients diagnosed pre-mortem was 75 (47-94) years, and 91% were male (31% vs. 9%, p < 0.001). Presenting signs and symptoms included dyspnea and/or heart failure in 67% and atrial arrhythmias in 62%. Median overall survival from diagnosis was 3.6 years and did not change over time. Multivariate predictors of mortality included age, ejection fraction, pericardial effusion, N-terminal pro–B-type natriuretic peptide (NT-proBNP), and troponin T. A staging system was developed using thresholds of troponin T (0.05 ng/ml) and NT-proBNP (3000 pg/ml). The respective 4-year overall survival estimates were 57%, 42%, and 18% for stage I (both values below cutoff), stage II (one above), and Stage III (both above). Stage III patients were at an increased risk of mortality after adjustment for age and gender compared to stage I (HR 3.6, p < 0.001).

Conclusions:

The authors concluded that the natural history of ATTRwt is poor.

Perspective:

This study reports that ATTRwt is increasingly recognized as an important cause of heart failure and atrial arrhythmias. In addition, ATTRwt is associated with a poor prognosis and challenges the assumption that this is a disorder limited to elderly males, with significantly more female patients diagnosed post-mortem than ante-mortem. A simple cardiac biomarker staging system may provide important prognostic information and allow risk stratification. Additional studies are indicated to define the therapeutic implications of various biomarker profiles in patients with heart failure due to ATTRwt.

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

Keywords: Amyloid, Amyloid Neuropathies, Familial, Arrhythmias, Cardiac, Biological Markers, Dyspnea, Geriatrics, Heart Failure, Natriuretic Peptide, Brain, Peptide Fragments, Pericardial Effusion, Troponin T


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