Associations Between Right Ventricular Remodeling, Exercise and Circulating Metabolites in Volume and Pressure...

Area of Science:

• Cardiology
• Metabolomics
• Physiology

Background:

• Ventricular pressure and volume overload can alter myocardial function, exercise capacity, and metabolic pathways.
• Pulmonary arterial hypertension (PAH) represents a pressure overload state, while repaired tetralogy of Fallot (rTOF) with residual pulmonary regurgitation exemplifies a volume overload state.

Purpose of the Study:

• To investigate and compare the myocardial and metabolic alterations in PAH versus rTOF.
• To differentiate the effects of pressure overload (PAH) from volume overload (rTOF) on cardiac function and exercise capacity.

Main Methods:

• Cardiac magnetic resonance (CMR), cardiopulmonary exercise tests (CPET), and serum metabolomic profiling were performed on 227 subjects (103 controls, 67 rTOF, 57 PAH).
• Key measurements included ventricular volumes, ejection fraction, longitudinal strain, and peak oxygen uptake (PVo2).

Main Results:

• rTOF showed greater right ventricular (RV) remodeling than PAH. Both conditions impaired RV function and exercise tolerance (PVo2).
• Elevated branched-chain amino acids in rTOF correlated with impaired RV function.
• Elevated dimethylglycine in PAH correlated with RV remodeling and dysfunction.

Conclusions:

• PAH and rTOF exhibit distinct RV remodeling patterns and exercise intolerance.
• Metabolic differences, including branched-chain amino acids and one-carbon metabolites, distinguish PAH, rTOF, and control groups.