Digoxin sensitivity in amyloid cardiomyopathy.

Abstract

Digoxin (5 mg/ml) was added to 10-mg and 20-mg pellets of purified primary and secondary amyloid fibrils, a normal human liver and heart homogenate and a homogenate from the heart of a patient with amyloid cardiomyopathy who had not received digitalis. After centrifugation, the supernatants were recovered and assayed for digoxin concentrations. Aliquots from the sediments were studied for the presence of digoxin, using rabbits antidigoxin antiserum and an indirect immunofluorescent technique. The results showed that 0.11--0.13 ng/ml of digoxin bound per milligram of fibrils and could not be separated by repeated washings. Elution with citrate or changes in the pH of the buffer. Immunofluorescent studies demonstrated diffusely bright immunofluorescence with the fibril preparation and amyloid heart homogenate when reacted with digoxin and digoxin-specific antiserum. These studies demonstrate that isolated amyloid fibrils bind digoxin and suggest that this interaction may play some role in the sensitivity to digitalis that has been observed in some patients with amyloid cardiomyopathy.

Diagnosis and Management of the Cardiac Amyloidoses

“…74 As a result of the binding to myocardial amyloid, cardiac digoxin levels may be elevated, and digoxin toxicity can exist even in the setting of "therapeutic" serum digoxin levels. Nevertheless, when atrial fibrillation with a rapid ventricular response is present, digoxin (administered cautiously) can be usually safely and successfully used.…”

Cardiac Amyloidosis Associated With a Novel Transthyretin Aspartic Acid-18 Glutamic Acid De Novo Mutation

“…Echocardiographic tracking over the 5 years of follow-up showed thickening of the RV wall, decreased RV wall motion and an increase in the size of RV chamber, which are all consistent with predominantly right-sided heart failure in patients with cardiac amyloidosis. 15 Patients with cardiac amyloidosis can become sensitized to digoxin, 10 which binds to amyloid fibrils, 16 and despite very cautious administration, this occurred in the present patient. ACEI and -blockers failed to control the heart failure because of further weakness and hypotension.…”

Stiff Heart Syndrome

“…7 However, the propensity of digoxin to bind with amyloid protein fibrils increases its availability and causes digoxin toxicity, even at therapeutic digoxin levels. 49 Pacemakers have been used in patients with symptomatic bradycardia. The atrial and ventricular pacing thresholds have been shown to be higher in these patients.…”