Excess ventilation and chemosensitivity in patients with inefficient ventilation and chronic coronary syndrome or heart failure: a case-control study.

Background: In patients with chronic coronary syndromes (CCS), increased ventilation/carbon dioxide production ( $\dot{V}$ _E/ $\dot{V}$ CO₂) slope has been found to predict disease progression and mortality, similarly to patients with heart failure (HF); however, increased chemosensitivity, a well-established predictor for mortality in patients with HF, has rarely been assessed in patients with CCS.

Method: Patients with CCS, HF with reduced ejection fraction (EF < 50%), healthy controls (45+ years), and young healthy adults (<35 years) were recruited. For patients, a $\dot{V}$ _E/ $\dot{V}$ CO₂ slope ≥36 was an inclusion criterion. The Duffin rebreathing method was used to determine the resting end-expiratory partial pressure of carbon dioxide (P_ETCO₂), ventilatory recruitment threshold (VRT), and slope (sensitivity) during a hyperoxic (150 mmHg O₂) and hypoxic (50 mmHg O₂) rebreathing test to determine the central and peripheral chemosensitivity.

Results: In patients with CCS, HF, controls, and young healthy adults, median $\dot{V}$ _E/ $\dot{V}$ CO₂ slopes were 40.2, 41.3, 30.5, and 28.0, respectively. Both patient groups had similarly reduced hyperoxic VRT (at P_ETCO₂ 42.1 and 43.2 mmHg) compared to 46.0 and 48.8 mmHg in the control and young healthy adults. Neither hypoxic VRT nor hyper- or hypoxic slopes were significantly different in patients compared to controls. Both patient groups had lower resting P_ETCO₂ than controls, but only patients with HF had increased breathing frequency and rapid shallow breathing at rest.

Conclusion: In patients with HF and/or CCS and excess ventilation, central chemoreflex VRT was reduced independently of the presence of HF. Low VRTs were related to resting excess ventilation in patients with CCS or HF; however, rapid shallow breathing at peak exercise was present only in patients with HF.

Clinical trial registration number: NCT05057884.