Cardiopulmonary Sleep Spectrograms Open a Novel Window Into Sleep Biology-Implications for Health and Disease

Abstract

The interactions of heart rate variability and respiratory rate and tidal volume fluctuations provide key information about normal and abnormal sleep. A set of metrics can be computed by analysis of coupling and coherence of these signals, cardiopulmonary coupling (CPC). There are several forms of CPC, which may provide information about normal sleep physiology, and pathological sleep states ranging from insomnia to sleep apnea and hypertension. As CPC may be computed from reduced or limited signals such as the electrocardiogram or photoplethysmogram (PPG) vs. full polysomnography, wide application including in wearable and non-contact devices is possible. When computed from PPG, which may be acquired from oximetry alone, an automated apnea hypopnea index derived from CPC-oximetry can be calculated. Sleep profiling using CPC demonstrates the impact of stable and unstable sleep on insomnia (exaggerated variability), hypertension (unstable sleep as risk factor), improved glucose handling (associated with stable sleep), drug effects (benzodiazepines increase sleep stability), sleep apnea phenotypes (obstructive vs. central sleep apnea), sleep fragmentations due to psychiatric disorders (increased unstable sleep in depression).

Keywords: cardiopulmonary coupling (CPC); heart rate variability; insomnia; sleep apnea; stable sleep.

FIGURE 1

Schematic for CPC analysis. ECG, Electrocardiogram; PPG, Photoplethysmogram; EDR, ECG-derived respiration; PDR, Photoplethysmogram derived respiration R-S and QRS are ECG waveforms; N-N intervals, Normal sinus to normal sinus intervals; Hz, frequency; HFC, high frequency coupling; LFC, low frequency coupling.

FIGURE 2

Photoplethysmogram/oximetry-based CPC-heart rate analysis. The oximetry-based analysis provides a full CPC-sleep spectrogram, an apnea-hypopnea index by integrating CPC LFC and oxygen desaturation events, and a profile of heart rate across the night. In the upper segment of the figure, “dipping” of heart rate is noted along with abundant high frequency coupling/stable sleep. In the lower sample, there is less stable state, but the heart rate profile is distinctly abnormal, with an elevation even during stable state. Such relative tachycardia during stable NREM sleep may suggest obstructive hypoventilation. In both examples, oxygen desaturation itself is mild. Stable and unstable sleep (HFC and LFC, respectively) occur intermittently through the night. HFC, high frequency coupling; LFC, low frequency coupling; e-LFC, elevated low frequency coupling; HR, heart rate; CHVR, cyclic heart rate variation.

FIGURE 3

The oximeter-extracted CPC spectrogram. The basic graphical representation of the CPC-spectrogram has high, low, and very low frequency coupling (HFC, LFC, and VLFC, respectively) components. Actigraphy is integrated, and VLFC without movement is considered REM sleep, whereas VLFC with movement is Wake. Cyclic variation of heart rate is also displayed, as well as e-LFC as a measure of sleep fragmentation. The oximeter signal itself provides standard oximetry metrics, such as an oxygen desaturation index. As shows, periods of HFC and LFC alternate throughout the night. LFC, low frequency coupling; VLFC, very low frequency coupling; HFC, high frequency coupling; CHVR, cyclic heart rate variation.

FIGURE 4

Sleep apnea phenotyping. 3-Dimensional graphical view of the CPC- spectrogram in a patient with severe sleep apnea and no stable (HFC) sleep. Color code: orange = VLFC, blue = e-LFC_BB (broadband coupling), and red = e-LFC_NB (narrowband coupling). The offset view (right) shows the narrow dispersion of coupling frequencies induced by periodic breathing toward the end of the recording period, while earlier in the night the e-LFC spectra are “broadly dispersed,” consistent with predominantly obstructive sleep apnea. On the figure to the right the time axis is cut off and the figure is off set to show the narrow band best.