Decrease in exhaled hydrogen as marker of congestive heart failure

Abstract

Objective: Hydrogen excretion is thought to be related to systemic antioxidation activity. H₂ selectively reduces the hydroxyl radical of free hydrogen (·OH), a highly cytotoxic form of reactive oxygen species, in cultured cells.

Methods: We investigated whether exhaled H₂ decreased during night sleep, reflected ·OH production and was associated with heart failure severity. We enrolled 108 patients with chronic heart failure (CHF) and 15 control participants without CHF. H₂ concentration was measured by gas chromatography in exhaled breath collected before sleep and in the morning after overnight fasting. Overnight change in H₂ concentration (ΔH₂) was calculated. Mitochondrial morphology evaluated by transmission electron microscopy in endomyocardial biopsies collected from 18 patients with dilated cardiomyopathy.

Results: ΔH₂ was significantly lower in patients with CHF compared with controls (-4.3±1.0 vs 2.0±2.1 ppm, p=0.030) and was positively correlated with cardiac index (CI; r = -0.285, p=0.003). Patients with a ΔH₂<0 ppm had a significantly lower CI compared with those who had a ΔH₂>0 ppm (2.85±0.61 vs 3.24±0.65 L/min/m², p=0.005). ΔH₂ was negatively correlated with both the percentage of vacuole-containing mitochondria and indices of cristae remodelling (r = -0.61, p=0.007).

Conclusions: Decrease in exhaled H₂ during night sleep was associated with CHF severity. ΔH₂ warrants investigation as marker of CHF severity.

Keywords: heart failure ▪ Idiopathic dilated cardiomyopathy.

Figure 1

Representative electron micrograph of an endomyocardial specimen biopsied from a patient with dilated cardiomyopathy. Ultrastructural analysis to determine the percentage of mitochondria with vacuoles (arrowheads) was done to evaluate the extent of mitochondrial damage.

Figure 2

Assay of exhaled hydrogen (H₂) in patients with chronic heart failure (CHF) and control participants. No significant differences in exhaled H₂ concentration were observed before sleep (orange bars). The morning H₂ concentration was lower in patients with CHF than in control group (green bars; p=0.003). A significant overnight decrease in exhaled H₂ concentration was observed in CHF group (p<0.001).

Figure 3

Correlation of change in H₂ concentration (△H₂) haemodynamics or laboratory parameters. (A) ΔH₂ was positively correlated with cardiac index (CI; r=0.285, p=0.003). (B) ΔH₂ was negatively correlated with high-sensitivity troponin T (hsTnT; r =−0.324, p=0.001). (C) ΔH₂ was negatively correlated with C-reactive protein (CRP; r=−0.240, p=0.012).

Figure 4

Comparison of cardiac index (CI) in patients with overnight decreased exhaled hydrogen (H₂) concentration and increased exhaled H₂ concentration. CI was significantly lower in the decreased exhaled H₂ than in the other group (2.85±0.61 vs 3.24±0.65 L/min/m², p=0.005). Data are means±SD.

Figure 5

The percentage of mitochondria in endomyocardial tissue cells with vacuoles and overnight change in H₂ concentration had a significant positive correlation (r=−0.61, p=0.007).