Altered Peripheral Blood Mononuclear Cell (PBMC) Mitochondrial Coupling and Complex IV Respiration in Severe Aortic Stenosis Before and After Transcatheter Aortic Valve Replacement (TAVR)

Background: Circulating peripheral blood mononuclear cell (PBMC) mitochondrial respiration is impaired in heart failure and transplanted patients. Severe aortic stenosis (AS), characterized by pressure overload leading to cardiac mitochondrial dysfunction, might also be associated with PBMC mitochondrial respiration alterations, likely related to systemic inflammation and left heart hypertrophy and diastolic dysfunction. Population and Methods: We determined PBMC mitochondrial respiration by high-resolution respirometry (Oroboros Instruments) in 9 healthy subjects and 25 AS patients before and until 30 days after transcatheter aortic valve replacement (TAVR) and investigated potential correlates with the clinical, biological and echocardiographic characteristics of the patients. Results: AS patients with a transaortic valvular gradient of 45 mm Hg were older and demonstrated slightly impaired renal function, inflammation markers, increased brain natriuretic peptide, left ventricular hypertrophy, and impaired diastolic function. PBMC mitochondrial coupling was decreased in the AS patients compared to controls (2.12 ± 0.10 vs. 2.76 ± 0.17, p = 0.003) and mitochondrial complex IV respiration was increased (31.07 ± 2.84 vs. 18.69 ± 2.09, p = 0.017). TAVR did not modify the alterations. Interestingly, increased complex IV mitochondrial respiration was associated with reduced mortality (p < 0.01). Conclusions: Severe aortic stenosis is associated with bioenergetic remodeling of circulating mononuclear cells that were not significantly associated with valvular hemodynamic impairment and ventricular function, before and after the mechanical relief of afterload. Nevertheless, future studies will be useful to determine whether such systemic immuno-metabolic phenotype, particularly PBMC mitochondrial complex IV respiration stimulation, may contribute to reduce the risk following TAVR.