Metabolic Dysregulation in Interstage Single Ventricle Heart Disease

Research study background  

To help infants with single ventricle heart disease live into adulthood, a series of three surgeries is often performed, starting in the first week of life and spanning over several years to reroute the blood: the Norwood procedure, Glenn procedure and Fontan procedure.

These surgeries come with risks for complications, particularly if their pulmonary vasculature (lung blood vessels) does not develop normally. A prospective cohort study published in 2023 evaluated the circulating metabolome of interstage infants with single ventricle heart disease prior to the Glenn procedure and determined whether metabolite levels were associated with pulmonary vascular inadequacy. (The time between the first and second surgeries in these patients is called interstage, where infants share common physiology).

The study population included 52 infants undergoing stage 2 palliation and 48 healthy infants. Data collection and analysis involved targeted analysis of 175 metabolites, including pre-stage 2 infants, post-stage 2 infants and control serum samples. Clinical variables were extracted from medical records.

Findings

• 74 of the metabolites were different between patients with single ventricle heart disease and controls. 
• 27 of 39 metabolic pathways were altered, including pentose phosphate and arginine metabolism  
• 71 metabolites were different in single ventricle heart disease between timepoints.  
• Of the 39 pathways analyzed, 33 were altered postoperatively, including arginine and tryptophan metabolism.  
• Trends toward increased pre-operative methionine metabolites in patients with:   
• Higher pulmonary vascular resistance  
• Higher postoperative tryptophan metabolites in patients with greater postoperative hypoxemia

Conclusions

The study demonstrated that circulating metabolome of interstage single ventricle heart disease infants is significantly different than controls and is further disrupted after stage 2. Several metabolites trended toward a link to adverse outcomes.

Study authors concluded that metabolic dysregulation may be an important factor in early single ventricle heart disease pathobiology.