Abstract 19293: Removal of Dietary Trimethylamine N-Oxide (TMAO) Attenuates Cardiac Dysfunction in Pressure Overload Induced Heart Failure
Rationale: Patients at increased risk for heart attack and adverse prognosis during heart failure have increased levels of circulating trimethylamine N-oxide (TMAO), a metabolite formed in the metabolism of dietary phosphatidylcholine.
Objective: We investigated the effects of withdrawing dietary TMAO from diet on the progression of heart failure following transverse aortic constriction (TAC).
Methods and Results: Male C57BLK/6J mice were fed either control diet or a diet containing TMAO (0.12%) starting at 3 weeks prior to surgical TAC and were studied for 17 weeks. At 6 weeks post TAC a subset of animals of the 0.12% TMAO diet were switch to control diet for the remainder of the study. Left ventricular (LV) structure and function were monitored at 3 week intervals and myocardial tissue and blood samples were collected at 17 weeks. Circulating BNP levels were significantly (p < 0.01) higher in the 0.12% TMAO group compared to control. Left ventricular ejection fraction (LVEF) was significantly (p < 0.05) attenuated in mice fed TMAO compared to control diet. However in mice that had dietary TMAO withdrawn, LVEF was significantly (p < 0.05) improved compared to mice maintained on 0.12% TMAO diet. LV end-diastolic and end-systolic diameters were significantly (p < 0.05) increased in the TMAO group compared to control diet. Withdrawing dietary TMAO following exposure significantly (p < 0.05) attenuated this effect.
Conclusions: These data demonstrate that heart failure severity is significantly enhanced in mice fed diets containing TMAO. Our results suggest that removing this toxic metabolite from diet improves cardiac function and remodeling in the setting of heart failure in mice.
Author Disclosures: C.L. Organ: None. Z. Li: None. C. Zibilich: None. W. Tang: None. S.L. Hazen: None. D.J. Lefer: None.
- © 2016 by American Heart Association, Inc.