Digoxin Use in Cardiac Amyloidosis

Abstract

Introduction With limited options for rate control of atrial fibrillation in the setting of low-output heart failure (HF), digoxin may appear to be a reasonable option for patients with cardiac amyloidosis (CA). However, current guidelines, based on historical case reports and an in vitro study, state that digoxin should generally be avoided in CA due to increased sensitivity for digoxin toxicity. A recent study of 107 patients with AL amyloidosis given digoxin showed relative safety with cautious use, with 11% of patients developing significant arrhythmias. We describe our institution's experience with digoxin in patients with CA and the suspected digoxin-related arrhythmias and toxicity. Methods This is a retrospective examination of patients diagnosed with CA seen between November 1995 and October 2018 at the Cleveland Clinic. CA patients were screened for a history of digoxin use; patients with less than 7 days of digoxin use were excluded, as well as those with incomplete medical records. Suspected digoxin-related arrhythmias and toxicity events were defined as: unexplained altered mental status, use of digoxin immune fab, ventricular tachycardia/fibrillation, paroxysmal atrial tachycardia with 2:1 block, new-onset junctional rhythm, and symptomatic bradycardia. Results Of 756 patients with CA identified, 71 patients were treated with digoxin for ≥7 days: 42 with transthyretin (ATTR) CA and 29 with light chain (AL) CA. Median duration of digoxin therapy was 10 months (IQR 3-38) for the ATTR-CA cohort and 2 months (IQR 1-7) for the AL-CA cohort. Digoxin was used for rate control of atrial fibrillation in 66% of the total population (64% ATTR, 69% AL) and management of symptomatic HF in 34% (36% ATTR, 31% AL). Suspected digoxin-related arrhythmias and toxicity occurred in 10%, described in detail in Table 1. 21% of the digoxin population died while on therapy, but only one death may have been attributed to digoxin use or toxicity. Conclusions In carefully-selected patients with CA treated with digoxin, 90% did not have a digoxin-related adverse event over a median treatment duration of 10 months. 10% had an adverse event potentially attributable to digoxin, with one death that may or may not have been related. Despite current guidelines, digoxin may be used cautiously in selected patients with ATTR- or AL-CA who have no good options for rate control in atrial fibrillation or for low output heart failure. Risks and benefits of using digoxin in CA should be evaluated on a patient by patient basis.