Difference between ejection times measured at two different peripheral locations as a novel marker of vascular stiffness

<div><p>Pulse wave velocity (PWV) has been recommended as an arterial damage assessment tool and a surrogate of arterial stiffness. However, the current technology does not allow to measure PWV both continuously and in real-time. We reported previously that peripherally measured ejection time (ET) overestimates ET measured centrally. This difference in ET is associated with the inherent vascular properties of the vessel. In the current study we examined ETs derived from plethysmography simultaneously at different peripheral locations and examined the influence of the underlying arterial properties on ET prolongation by changing the subject’s position. We calculated the ET difference between two peripheral locations (ΔET) and its corresponding PWV for the same heartbeat. The ΔET increased with a corresponding decrease in PWV. The difference between ΔET in the supine and standing (which we call ET index) was higher in young subjects with low mean arterial pressure and low PWV. These results suggest that the difference in ET between two peripheral locations in the supine vs standing positions represents the underlying vascular properties. We propose ΔET in the supine position as a potential novel real-time continuous and non-invasive parameter of vascular properties, and the ET index as a potential non-invasive parameter of vascular reactivity.</p></div

Demographics, baseline characteristics, values of PWV_{ΔPAT Toe-Finger}, ΔPWV_{Standing-Supine}, ΔET _Toe-Finger, ET index and group assignment based on ET index of the subjects.

<p>Demographics, baseline characteristics, values of PWV_{ΔPAT Toe-Finger}, ΔPWV_{Standing-Supine}, ΔET _Toe-Finger, ET index and group assignment based on ET index of the subjects.</p

The comparison between group 1 and group 2.

<p>Subjects were divided into two groups according to their percentile rank of the ET index: group 1 had low ET index and group 2 had high ET index (A). Each graph showing the distribution of age (B), BMI (C), HR in supine (D), MAP supine (E), PWV_{ΔPAT Toe-Finger} supine (F), and ΔPWV_{Standing-Supine} (G) in group 1 and group 2. Each graph represents the individual data points and superimposes a horizontal line at the arithmetic mean; error bars showing plus and minus one SD. ET: ejection time; BMI: body mass index; HR: heart rate; MAP: mean arterial pressure; PWV: pulse wave velocity; SD: standard deviation.</p

Effect of position and peripheral location on the measured ET.

<p>Each plot indicates the mean ET calculated from each individual subject. (A) ETs measured at the ear. (B) ETs measured at the finger. (C) ETs measured at the toe. (D) ETs measured in the standing position. (E) ETs measured in the sitting position. (F) ETs measured in the supine position. ET: ejection time, ns: not significant, *: P < 0.05, ***: P < 0.001.</p

Bland-Altman plots of the difference between ETs measured at two peripheral locations.

<p>Bland Altman plots showing the difference between ET at the finger and ET at the ear (A)(D)(G), between ET at the toe and ET at the finger (B)(E)(H), and between ET at the toe and ET at the ear (C)(F)(I). Each ET was measured in the standing (A)(B)(C), sitting (D)(E)(F), and supine (G)(H)(I) position. The solid line indicates the mean of difference, and the dashed line indicates the 95% limits of agreement. The difference of ETs between each pair of locations are also shown in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0187781#pone.0187781.t002" target="_blank">Table 2</a> (ΔET). ET: ejection time; SD: standard deviation.</p

Relationship between ΔET, PWV_ΔPAT, and PWV_ΔDAT.

<p>The relationship between ΔET and PWV_ΔPAT (A, D, G), between ΔET and PWV_ΔDAT (B, E, H), between PWV_ΔDAT and PWV_ΔPAT (C, F, I) for each pair of locations (Toe-Ear: A, B, C; Toe-Finger: D, E, F; Finger-Ear: G, H, I). Each individual subject has three dots on each graph which indicate mean values derived from the standing (black circle), sitting (gray triangle) and supine (white square) positions. The dashed line indicates the hyperbolic or linear regression line. The regression equation and the coefficient of determination (R²) are presented in each graph. ET: ejection time; PWV: pulse wave velocity; PAT: pulse arrival time; DAT: dicrotic notch arrival time.</p

Relationship between ΔET_Toe-Finger, ΔPAT_Toe-Finger and ΔDAT_Toe-Finger in an individual subject.

<p>(A), (B), and (C) Measurements derived from a 23 year old female with the most compliant vasculature as evident by the lowest PWV_{ΔPAT Toe-Finger} in the supine position. (D), (E), and (F) Measurements derived from a 36 year old female with the least compliant vasculature as evident by highest PWV_{ΔPAT Toe-Finger} in the supine position. Each dot on the graph was derived from a single heartbeat in the standing (black circles) and supine (white squares) positions. (A) and (D) Scatter plot of ΔET_Toe-Finger and ΔPAT_Toe-Finger. (B) and (E) Scatter plot of ΔET_Toe-Finger and ΔDAT_Toe-Finger. (C) and (F) Scatter plot of ΔDAT_Toe-Finger and ΔPAT_Toe-Finger. ET: ejection time; PAT: pulse arrival time; DAT: dicrotic notch arrival time, PWV: pulse wave velocity.</p

The relationship between the ET index and age, BMI, HR, MAP, PWV_{ΔPAT Toe-Finger}, and ΔPWV_{Standing-Supine}.

<p>The ET index was calculated by subtracting the mean ΔET_Toe-Finger in the standing position from the mean ΔET_Toe-Finger in the supine position for each individual subject. The dashed line indicates the simple linear regression line. The regression equation, the coefficient of determination (R²), and P value are presented. (A) ET index as a function of age. (B) ET index as a function of BMI. (C) ET index as a function of HR measured in the supine position. (D) ET index as a function of MAP measured in the supine position. (E) The ET index as a function of PWV_{ΔPAT Toe-Finger} in the supine position. (F) The ET index as a function of ΔPWV_{Standing-Supine}. ΔPWV_{Standing-Supine} was calculated as the difference between PWV_{ΔPAT Toe-Finger} in the supine and standing position. ET: ejection time; BMI: body mass index; HR: heart rate; MAP: mean arterial pressure; PWV: pulse wave velocity.</p

GLM analysis.

<p>GLM analysis.</p

Mean±SD of RR interval, ET, ΔET, ΔPAT, ΔDAT and PWV in 3 positions.

<p>Mean±SD of RR interval, ET, ΔET, ΔPAT, ΔDAT and PWV in 3 positions.</p