Despite a substantial therapeutic arsenal to treat patients affected by heart failure (HF), no treatment targets alterations of cardiac energy metabolism and mitochondrial functions even though their involvement in HF pathophysiology has been demonstrated for years.

This study proposes to evaluate the efficacy of a B vitamin cocktail (3VITB) added to diet (B3, B9 and B12) to restore energy metabolism in an animal model of established HF.

HF was induced by transverse aortic constriction (TAC) in male and female C57Bl6N mice. Four weeks after surgery, 3VITB treatment or placebo (control diet) were introduced and the mice were randomized into 3 groups: Sham, TAC+vehicle, and TAC+3VITB. Mice were followed up for 16 weeks of treatment to monitor survival, weight, cardiac function, and exercise tolerance or sacrificed after 8 weeks of treatment for histology, biochemical measurement, and mitochondrial function assessment.

TAC+3VITB males showed an improvement in survival compared to TAC+vehicle (117.8±10.93 days vs. 74.31±10.95 days, P<0.01). This was associated with: (i) a preservation of cardiac function as shown by a slower drop in ejection fraction (EF) (–0.13±0.027% vs. –0.34±0.058%, EF loss per days of survival); (ii) an increased maximum running time in treadmill exertion test (13.5±0.69min vs. 10.2±0.61min); (iii) a reduction in cardiac hypertrophy (heart weight to tibia length ratio: 11.9±0.69 vs. 15.8±1.36); (iv) a reduction in interstitial fibrosis (1.7±0.09% vs. 2.8±0.22%); (v) a preservation of mitochondrial complex I+II-dependent respiration in cardiac permeabilized fibers (44.6±3.27nmolO₂/min/mg vs. 34.6±3.25nmolO₂/min/mg of dry tissue); (vi) a protection of citrate synthase activity (2218±254IU/g prot vs. 1191±54.35IU/g prot); and (vii) an increase in TFAM and NRF1 markers of mitochondrial biogenesis. In females, survival and cardiac function were less affected. The 3VITB, reduced cardiac hypertrophy, enhanced capacity in exertion test and increased mitochondrial function and markers.

This study demonstrated the efficacy of 3VITB to preserved cardiac function and energy metabolism in a murin HF model especially in males that are more sensitive to cardiac pressure overload. This work confers credit to vitamin supplementation and to metabolic therapy in the frame of HF treatment.