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This protocol integrated near-infrared spectroscopy into conventional cardiopulmonary exercise testing to identify the involvement of the cerebral hemodynamic response in exercise intolerance in patients with heart failure.
Cerebral hypo-oxygenation during rest or exercise negatively impacts the exercise capacity of patients with heart failure with reduced ejection fraction (HF). However, in clinical cardiopulmonary exercise testing (CPET), cerebral hemodynamics is not assessed. NIRS is used to measure cerebral tissue oxygen saturation (SctO2) in the frontal lobe. This method is reliable and valid and has been utilized in several studies. SctO2 is lower during both rest and peak exercise in patients with HF than in healthy controls (66.3 ± 13.3% and 63.4 ± 13.8% vs. 73.1 ± 2.8% and 72 ± 3.2%). SctO2 at rest is significantly linearly correlated with peak VO2 (r = 0.602), oxygen uptake efficiency slope (r = 0.501), and brain natriuretic peptide (r = -0.492), all of which are recognized prognostic and disease severity markers, indicating its potential prognostic value. SctO2 is determined mainly by end-tidal CO2 pressure, mean arterial pressure, and hemoglobin in the HF population. This article demonstrates a protocol that integrates SctO2 using NIRS into incremental CPET on a calibrated bicycle ergometer.
Cardiopulmonary exercise testing (CPET) has been applied in patients with heart failure with reduced ejection fraction (HF) for multiple aims, including the quantification of cardiopulmonary fitness, prognosis, diagnosing causes of exercise limitations, and exercise prescriptions1,2,3. During testing, hemodynamic variables and data derived from automatic gas exchange are monitored and analyzed. Cerebral tissue oxygen saturation (SctO2) monitoring has value for grading prognosis and disease severity4,5.
Near-infrared spectroscopy (NIRS) uses infrared light to penetrate the skull and estimate brain tissue oxygenation continuously and non-invasively6. Since oxyhemoglobin and deoxyhemoglobin have different light absorption spectra and are the primary chromophores that absorb light, their concentrations can be measured using light transmission and absorption6,7. However, background light absorbers also scatter light and may influence the measurement8. This study adopted a spatially resolved NIRS to measure SctO2 from rest to peak exercise9. Four wavelengths were emitted to compensate for wavelength-dependent scattering losses and eliminate background interference, thus enhancing accuracy10.
SctO2 represents the proportion of oxygen delivery vs. consumption in cerebral tissue. Cerebral desaturation is associated with disrupted cerebral blood flow (CBF), decreased arterial oxygen concentration, and increased cerebral tissue oxygen consumption11. Other than cardiac output insufficiency, advanced HF causes cerebral hypoperfusion during exercise by indirectly inducing cerebral vasoconstriction via diminishing arterial partial pressure of carbon dioxide (PaCO2) through hyperventilation12.
The clinical significance of cerebral oxygenation in HF was revealed by Chen et al.4. First, SctO2 was significantly decreased in the HF group compared with healthy controls. SctO2 is not only diminished at rest but also declined further during exercise. It is not observed in the healthy group. Second, SctO2rest and SctO2peak were correlated with VO2peak, brain natriuretic peptide (BNP), and oxygen uptake efficiency slope (OUES), all of which are established prognostic markers. Therefore, SctO2rest and SctO2peak are very likely to be prognostic and reflect disease severity in HF patients. Another study by Koike et al. suggested that the change in cerebral oxyhemoglobin measured at the forehead from rest to peak exercise was significantly lower in non-survivors compared to that in survivors of patients with coronary artery disease5. Hence, cerebral oxygenation may be employed to stratify the disease severity and prognosis of patients with HF.
The following protocol was approved by the ethics committee in Chang Gung Memorial Hospital, Linkou, Taiwan. The exercise test was carried out in an air-conditioned laboratory with an atmospheric temperature of 22-25 °C, pressure of 755 to 770 Torr, and relative humidity of 55-65%. Before each test, the gas analyzer was calibrated following the manufacturer's instructions using room air and a gas mixture of known concentration (FO2: 0.12; FCO2: 0.05; N2 as balance). The turbine flow meter of the system was calibrated by the 2-point method with 0.2 L/s and 2 L/s by an automatically-pumping system.
1. Preparation: Placement of sensors and recorders
2. CPET and SctO2 monitoring
Thirty-four HF patients and 17 healthy controls were enrolled at Linkou Chang Gung Memorial Hospital, Taiwan. Each subject underwent cardiopulmonary exercise testing that incorporated SctO2 monitoring by NIRS. Briefly, SctO2 (rest; peak) values were significantly lower in the HF group (66.3 ± 13.3%; 63.4 ± 13.8%,) than in the control (73.1 ± 2.8%; 72 ± 3.2%) group (Figure 1). In the HF group, SctO2 at rest ...
Cerebral oxygenation monitored noninvasively and continuously by NIRS has been applied in various scenarios, including cardiovascular surgery13 and brain functional analyses such as those that estimate neural activity14. This protocol integrated NIRS into conventional CPET to identify the involvement of the cerebral hemodynamic response in exercise intolerance in patients with HF. It increases the value of exercise testing in determining prognosis and disease severity.
...The authors have nothing to disclose.
The patient who participated in exercise testing is deeply appreciated. This research was supported by National Science Council, Taiwan (NMRPG3G6231/2/3), Chang Gung Memorial Hospital (Grant No. CMRPG3G0601/2), and Healthy Aging Research Center, Chang Gung University and the Taiwan Ministry of Education's Higher Education Deep Plowing Program (Grant Numbers EMRPD1H0351 and EMRPD1H0551).
Name | Company | Catalog Number | Comments |
Bicycle ergometer | Ergoline, Germany | Ergoselect 150P | |
Cardiopulmonary exercise testing gas analysis | Cardinal-health Germany | MasterScreen CPX | |
Finger pulse oximetry | Nonin Onyx, Plymouth, Minnesota | Model 9500 | |
Sphygmomanometer | SunTech Medical, UK | Tango |
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