Redistribution of cardiac output during exercise by functional mitral regurgitation in heart failure: compensatory O2 peripheral uptake to delivery failure

Abstract

Functional mitral regurgitation (MR) is prognostic in heart failure (HF). MR favors an nonphysiological exercise central cardiac output (CO) redistribution which adds to oxygen (O₂) delivery failure. The consequences of this redistribution in O₂ supply have not been explored previously. We aimed at evaluating the putative role of cardiac output (CO) and O₂ arteriovenous [C(a-v)O₂] difference in the attained peak V̇o₂ in advanced HF with reduced ejection fraction (HFrEF) and MR. 134 HFrEF patients and 80 controls with no HF underwent exercise gas exchange combined with CO and C(a-v)O₂ estimated by echo-Doppler technique. The HF population was divided into two groups: HF with severe rest MR (MR+ group; n = 36) and no to mild MR (MR- group; n = 98). HF groups did not differ in rest CO (MR+ vs. MR- 3.4 ± 1.8 vs. 3.8 ± 1.0 L/min; P = 0.32) and showed a trend for a higher C(a-v)O₂ at rest (9.0 ± 4.0 vs. 8.0 ± 2.0 mL O₂/100 mL; P = 0.14). In HF, CO and C(a-v)O₂ at rest were significantly lower and higher compared with controls. At peak exercise, MR+ compared with MR- exhibited a significant reduction in peak V̇o₂ 11.6 ± 3.0 vs. 13.7 ± 3.6 ml O₂·kg^-1·min^-1; P < 0.01) with a lower O₂ delivery (CO: 5.2 ± 3.3 vs. 7.0 ± 2.0 L/min; P < 0.01), which was partially compensated by a significantly greater O₂ extraction [C(a-v)O₂, 18 ± 5 vs. 15 ± 4 mL O₂/100 mL; P < 0.01]. In HFrEF, severe MR is associated with impaired O₂ delivery due to CO redistribution to the pulmonary circulation. C(a-v)O₂ is maximalized to compensate for the reduced O₂ delivery. This novel information is relevant to phenotyping and targeting mediators of functional response in HF. Specifically, findings provide directions in the understanding at which extent mitral valve repair would restore an efficient cardiac reserve by enhancing O₂ delivery during exercise, likely contributing to symptom relief and hopefully impacting the clinical trajectory of HF syndrome with secondary MR.NEW & NOTEWORTHY This is an analysis involving 134 heart failure patients with reduced ejection fraction versus 80 controls investigated during functional evaluation with gas exchange and hemodynamic, addressing the severe MR phenotype and testing the hypothesis that the backward cardiac output redistribution to the lung during exercise impairs delivery and overexpresses peripheral extraction. This information is new and has important implications in the management of heart failure.

Keywords: HFrEF; arterovenous O2 difference; cardiac output; mitral regurgitation.