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 (V-E/VCO2) 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 V-E/VCO2 slope >= 36 was an inclusion criterion. The Duffin rebreathing method was used to determine the resting end-expiratory partial pressure of carbon dioxide (PETCO2), ventilatory recruitment threshold (VRT), and slope (sensitivity) during a hyperoxic (150 mmHg O-2) and hypoxic (50 mmHg O-2) rebreathing test to determine the central and peripheral chemosensitivity. Results: In patients with CCS, HF, controls, and young healthy adults, median V-E/VCO2 slopes were 40.2, 41.3, 30.5, and 28.0, respectively. Both patient groups had similarly reduced hyperoxic VRT (at PETCO2 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 PETCO2 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.