Wearable multimodal sensing for quantifying the cardiovascular autonomic effects of levodopa in parkinsonism

Figures

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  FIGURE 1. Overview of wearable sensing system and aims of this study. A wearable chest patch that measures electrocardiogram (ECG), seismocardiogram (SCG), and photoplethysmogram (PPG) signals was used in a population of Parkinson’s disease and multiple system atrophy during a clinical protocol and 24-h ambulatory study at home. Physiological markers related to cardiovascular autonomic function were extracted from the patch’s signals and were used to characterize the response to levodopa.

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  FIGURE 2. Clinical and at-home protocol overview. After a 12-h washout period, participants underwent autonomic testing followed by administration of their typical oral levodopa medication. The OFF-ON response was measured and then a 24-h period of continuous at-home monitoring was carried out. Participant diaries were used to provide event timestamps, including administration of medications.

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  FIGURE 3. Signal preprocessing and physiomarker extraction. The electrocardiogram (ECG), seismocardiogram (SCG), and photoplethysmogram (PPG) signals were initially filtered to their respective frequency bands where cardiovascular information is most prominent. From the ECG, R-peaks were located and used to extract normal-normal (NN) intervals, from which the other signals were segmented on a beat-by-beat basis. The quality of these beats was assessed using template distance metrics and amplitude outlier removal. The SCG and PPG beats were then ensemble-averaged before features were extracted from each heartbeat.

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  FIGURE 4. Notable levodopa-induced physiomarker changes and dose-response correlations. (A) Boxplots indicating significant physiomarkers changes from prior to levodopa (OFF) to an hour after (ON). Pre-ejection period (PEP), the ratio of PEP to left ventricular ejection time index (PEP/LVETi), seismocardiogram amplitude ( SCGamp ), and the low frequency band of heart rate variability (HRV-LF) are shown. (B) Correlation plots between the administered levodopa equivalent dosage (LED) and the magnitude of OFF-ON physiomarker changes in PEP/LVETi, PEP, LVETi, and photoplethysmogram amplitude ( PPGamp ) are depicted. Pearson’s r and Spearman’s ρ were used, depending on the distribution of the data. * padj< 0.05; † p < 0.05.

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  FIGURE 5. Comparison of levodopa responses between participants with orthostatic hypotension (OH) and without OH (no-OH). (A) Boxplots of the clinical levodopa responses are shown for the root-mean-square-of-successive-differences (RMSSD), standard deviation of normal-normal intervals (SDNN), and high frequency of heart rate variability (HRV-HF). (B) Boxplot of the difference in SDNN measured in the at-home responses. * padj< 0.05; † p < 0.05.

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  FIGURE 6. Case study of adverse levodopa reaction in participant with PD and OH. The participant initially experienced nausea about 40 min after taking levodopa, which worsened over the next 40 min. During this time, a drop in blood pressure (BP) from 134/85 mmHg (systolic/diastolic) to 73/44 mmHg was recorded. Concurrently, the wearable patch measured an increase in pulse arrival time (PAT) and pre-ejection period (PEP), which similarly indicates decreased arterial stiffness and decreased cardiac contractility given the stable heart rate (HR). After lying supine, the participant’s BP eventually surged (180/84 mmHg) and their symptoms dissipated. The marked responses in PAT and PEP, as well as the increase in photoplethysmogram amplitude ( PPGamp ), upon assuming a supine position further illustrate the return to a more normal physiological state.