Excess ventilation and chemosensitivity in patients with chronic coronary syndrome and patients with heart failure with reduced ejection fraction – a case control study
Authors: Prisca Eser , Dominic Kaesermann , Pietro Calamai , Anja Kalberer , Laura Stuetz , Sarina Huber , James Duffin , Matthias Wilhelm 
Published: August 2024

Background

In patients with chronic coronary syndromes (CCS) increased ventilation/carbon dioxide production (V̇E/V̇CO2) slope has been found to predict disease progression and mortality similarly to patients with heart failure (HF), however, chemosensitivity has rarely been assessed in patients with CCS.

Method

Patients with CCS, HF with reduced ejection fraction (EF<50%), old healthy (45+ years) and young adult healthy controls (<35 years) were recruited. For patients, a V̇E/V̇CO2slope ≥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 O2) and hypoxic (50 mmHg O2) rebreathing test to determine central and peripheral chemosensitivity.

Results

In patients with CCS, HF, and old and young controls, median V̇E/V̇CO2slopes were 40.2, 41.3, 30.5 and 28.0, respectively. Both patient groups had similarly reduced hyperoxic VRT (at PETCO242.1 and 43.2 mmHg) compared to 46.0 and 48.8 mmHg in the old and young controls. Neither hypoxic VRT nor hyper- or hypoxic slopes were significantly different in patients compared to controls. Both patient groups had lower resting PETCO2than controls, but only patients with HF had increased breathing frequency and rapid shallow breathing at rest.

Conclusion

In patients with cardiac disease and excess ventilation, central chemoreflex VRT was reduced independently of the presence of heart failure. Low VRTs were related to resting excess ventilation in patients with CCS or HF, however, rapid shallow breathing was present only in patients with HF.

Clinical perspective

What is new?

Excess ventilation during exercise and heightened chemosensory reflexes may be present not only in patients with HF but also in patients with CCS. This suggests that there is a gradual derangement of neurologic and/or hormonal factors leading to excess ventilation before the establishment of HF.

In patients with excess ventilation during exercise there is also excess ventilation at rest.

Excess ventilation in patients with CCS does not show the rapid shallow breathing pattern that is typical for patients with HF.

What are the clinical implications?

While excess ventilation during exercise causes dyspnoea with associated negative effects on exercise tolerance and quality of life,1excess ventilation at rest has been poorly investigated. More research is warranted as physiologic consequences may be substantial with the large time spent at rest compared to exercise.

The finding that the threshold of PETCO2at which ventilation starts to increase rather than the V̇E/PETCO2slope is increased in patients with inefficient ventilation suggests electrolyte derangement as an at least contributing cause which may stimulate alternative treatments such as intravenous iron therapy.2

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