Abstract 17179: Combined Doxycycline and Tauroursodeoxycholic Acid Slows Progression of Transthyretin Cardiac Amyloidosis
Introduction: Transthyretin (TTR) cardiac amyloidosis (CA) is a progressive infiltrative cardiomyopathy with no specific therapy. In animals, doxycycline disrupts existing amyloid fibrils and may prevent fibrillogenesis. Tauroursodeoxycholic acid (TUDCA), a bile acid, prevents extracellular TTR monomer deposits, and the 2 drugs work synergistically in a mouse model of amyloidosis to decrease tissue amyloid. We sought to determine whether a combination of TUDCA and doxycycline could slow the progression of amyloid-associated LV dysfunction in patients with TTR cardiac amyloidosis.
Methods: 17 patients with biopsy-proven TTR cardiac amyloidosis, mean age 71.3 yr (all men: 16 wild-type and 1 mutant TTR), received doxycycline 100 bid and TUDCA 250 mg tid for 12 months. The primary endpoint was change in longitudinal strain (LS) at 12 months, when compared to a group of 14 patients studied serially without therapy (mean age 72.4 yr, all men). All patients had echocardiograms performed on a GE Vivid machine, and analyzed by the same investigator. LS was measured from the apical 4-chamber view.
Results: Doxycycline/TUDCA was well-tolerated. Mean baseline LS was no different between treatment group and untreated patients, and both groups showed deterioration of LS at 12 months. However, deterioration of LS was less in the treated group than controls (table). NTproBNP, a marker of disease was measured in the treatment group only, and rose slightly from a mean of 3108 pg/ml to 3669 pg/ml,(p<0.05) consistent with the change in LS.
Conclusion: 1. TTR cardiac amyloidosis is characterized by a consistent decrease in LV strain over a 1 year period, associated with a rise in NTproBNP. 2. Although doxycycline/TUDCA combination does not entirely halt progression of LV dysfunction, it appears to significantly slow the progression of disease and offers a well-tolerated therapy for disease modification.
Author Disclosures: M. Sadegh: None. D.L. Trota: None. R.H. Falk: None.
- © 2015 by American Heart Association, Inc.