**6.3 Increased mitochondrial oxygen consumption is associated with poor cardiac outcomes in HLHS patients**

Oxygen consumption rate (OCR) from peripheral blood mononuclear cells in 16 biventricular-CHD (BV-CHD) patients, 20 single ventricle-CHD (SV-CHD) patients, and 22 healthy controls without CHD demonstrated higher respiratory maximum and reserve in single ventricle patients with poor cardiac outcome (death or cardiac death) [87]. Apart from that, we observed a lower OCR in HLHS patients with cardiac dysfunction compared with normal controls [87]. Of the 8 SV-CHD patients with Fontan completion, we observed significantly higher OCR in 4 patients with poor cardiac outcomes (death or cardiac death) (**Figure 9a** and **b**). These changes were observed in two related respiratory parameters—respiratory maximum and respiratory reserve. In contrast, SV-CHD patients with normal cardiac function showed significantly lower OCR when compared to either SV-CHD patients with HF, BV-CHD patients, or healthy controls (**Figure 9a** and **b**). Given SV-CHD with systemic RV are known to have worse clinical outcomes than SV-CHD patients with systemic LV [88–90], we reanalyzed the data focusing on only SV patients with HLHS (systemic RV), either with or without HF. This analysis yielded similar findings with significantly higher respiratory maximum and reserve observed in the post-Fontan HLHS patients with HF. However, we observed a lower OCR in HLHS patients without HF (**Figure 9c** and **d**). In addition, there is no difference between post-Fontan SV or HLHS patients either with or without HF when compared to BV-CHD patients or control subjects in basal glycolysis by measurement ECAR. Heart tissue from *Ohia* mutant mice with HLHS showed elevated
