Prevalence of Atrial Fibrillation and Thromboembolic Risk in Wild-Type Transthyretin Amyloid Cardiomyopathy
Authors: Syed Bukhari, Amr F. Barakat, Yvonne S. Eisele, Ricardo Nieves, Sandeep Jain, Samir Saba, William P. Follansbee, Amy Brownell, Prem Soman
Journal: Circulation (2021)

Wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM) results from the age-related myocardial deposition of transthyretin amyloid fibrils, leading to a toxic-restrictive cardiomyopathy and progressive heart failure. 1 Amyloid infiltration of the atria and myocardium is thought to predispose patients to atrial fibrillation (AF) and a high thromboembolic risk. 2 In this study, we sought to determine the prevalence of AF in patients with ATTRwt-CM and the incidence and predictors of systemic thromboembolism in patients with ATTRwt-CM and AF.This retrospective cohort study was approved by our instructional review board with a waiver of informed consent and included patients who were referred to our Cardiac Amyloidosis Center and underwent Tc-99m pyrophosphate (PYP) scintigraphy between June 1, 2015, and June 30, 2019.The study data will be made available to external researchers on request, subject to institutional approval.The diagnosis of ATTRwt-CM was established by positive Tc-99m PYP scintigraphy (defined as a planar grade ≥2 with diffuse myocardial tracer uptake on single photon emission computed tomography), negative serum studies for amyloid light chain amyloidosis (free serum kappa and lambda levels, serum kappa-to-lambda ratio, and serum immunofixation electrophoresis), and the absence of a transthyretin gene mutation. 3The diagnosis of AF was ascertained through chart review at the time of the Tc-99m PYP scintigraphy.The primary outcome was the incidence of systemic thromboembolism from the time of Tc-99m PYP scintigraphy to the last documented medical encounter at the time of chart review, which was performed in July 2020.Systemic thromboembolism was defined as a composite of ischemic stroke, transient ischemic attack, or peripheral embolism.Ischemic stroke was confirmed by computed tomography or magnetic resonance imaging.Transient ischemic attack was defined as transient neurologic dysfunction without evidence of infarction on brain imaging.Peripheral embolism was defined as arterial embolic occlusion of a limb confirmed by vascular imaging.The secondary outcomes included intracranial hemorrhage, major extracranial bleeding requiring hospital admission, and all-cause death.The predictors of thromboembolism were determined by Cox regression of covariates chosen on the basis of univariable significance and clinical relevance.Variables were added into the model sequentially on the basis of the strength of their univariable association and retained if the resulting likelihood ratio χ 2 value indicated an improvement in model fit (forward selection).All statistical analyses were performed using STATA version 12 (Stata Corp LP, College Station, TX).Of the 285 referred patients, 85 had a positive Tc-99m PYP scintigraphy and negative serum studies for amyloid light chain amyloidosis.Of these, 8 patients had a transthyretin gene mutation and were excluded.Thus, 77 patients Prevalence of Atrial Fibrillation and Thromboembolic Risk in Wild-Type Transthyretin Amyloid Cardiomyopathy