Estimation of left ventricular end-diastolic volume by left ventricular arterial coupling and stroke volume: A prospective, observational study

doi:10.21203/rs.3.rs-2083668/v1

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Estimation of left ventricular end-diastolic volume by left ventricular arterial coupling and stroke volume: A prospective, observational study

https://doi.org/10.21203/rs.3.rs-2083668/v1

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published 28 Apr, 2023

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Background

Left ventricular end-diastolic volume (Ved) is a major determinant of cardiac preload. However, its use in determination of fluid management is limited by lack of a simple means to measure it noninvasively. This study presents a new noninvasive method that was validated against simultaneously measured Ved by transthoracic echocardiography (TTE). The goal of this study was to develop and validate a method to estimate Ved in humans non-invasively from left ventricular arterial coupling (Ees/Ea) and stroke volume (SV).

Methods

Ees/Ea was approximated using four variables that can be measured noninvasively: end-systolic arterial pressure (Pes), diastolic arterial pressure (DBP), pre-ejection period (PEP), and ejection time (ET). A formula to derive Ved (Ved calc) using Ees/Ea was also devised. Ved measured using transthoracic echocardiography (Ved echo) was taken to be the actual value, and Ved calc and Ved echo were compared. The results are shown as mean values ± standard deviation.

Results

The 47 patients were 39 men and 8 women with a mean age of 24 ± 4 years, mean height of 169 ± 7 cm, and mean weight of 65 ± 12 kg. Ved echo was 91 ± 16 ml, and Ved calc was 102 ± 21 ml. There was a significant correlation between Ved echo and Ved calc (R² = 0.88, p < 0.01). A Bland–Altman plot between Ved echo and Ved calc showed that the bias was − 17.4 ml.

Conclusions

The results suggest that Ved can be measured non-invasively from Ees/Ea and SV.

Left ventricular end diastolic volume

Ees/Ea

stroke volume

The goal of fluid management is to maintain adequate end organ perfusion by optimizing stroke volume and cardiac output. Stroke volume (SV) depends on cardiac preload, afterload, and myocardial contractility. Therefore, preload assessment is important to determine the adequate fluid amount. Left ventricular end-diastolic volume (Ved) is a direct measure of cardiac preload. It has been reported that left ventricular end-diastolic area measured using transesophageal echocardiography is a reliable predictor of cardiac preload in patients with early septic shock.¹ However, the limitation of an ultrasound-based method is that it cannot perform continuous monitoring, and it relies on the proper acquisition and interpretation of the results. Currently, there is no clinical monitoring method to assess Ved noninvasively and continuously.

Left ventricular pressure volume relationships have been used to understand cardiac mechanics. End-systolic and end-diastolic pressure volume relationships (ESPVR and EDPVR) describe left ventricular systolic and diastolic properties, respectively. Ventricular-arterial coupling (V-A coupling), which is estimated from pressure volume loops, is expressed as the ratio of the end-systolic elastance (Ees) and the effective arterial elastance (Ea). Ees is the slope of the line connecting the end-systolic pressures (Pes) and volumes (Ves), such that Ees = Pes / (Ves - V0), where V0 is the volume at zero intraventricular pressure. Ea is defined as the slope of the line connecting end-diastolic volume on the volume axis to the end-systolic pressure volume point. Ea is the ratio between Pes and stroke volume. According to the definition of V-A coupling, Ved can be calculated from Ees/Ea and stroke volume.

A previous study introduced a noninvasive estimation of Ees/Ea using four parameters, namely pre-ejection period (PEP), ejection time (ET), end-systolic pressure (Pes), and diastolic pressure (Pd).² This method enabled us to estimate Ees/Ea beat to beat, because these four parameters can be obtained continuously using an electrocardiogram, pulse waveform, and phonocardiogram.

The aim of the present study was to estimate Ved using V-A coupling (Ees/Ea) in healthy subjects.

Study population

This was a prospective, observational study. The study protocol was approved by the Research Ethics Committee of the University of Fukui Hospital (No.20140125) and was conducted in accordance with the Declaration of Helsinki. Fifty-eight healthy adult patients were studied at the University of Fukui Hospital between 2018 and 2020. Subjects with a history of cardiovascular diseases were excluded. Informed consent was obtained from all participants and/or their legal guardian(s)

Measurements

Ave, sex, height, and weight of the subjects were recorded. Each subject was placed in the left lateral position, and transthoracic echocardiography was performed using Vivid E9 (GE Healthcare Japan, Tokyo, Japan). All acquisitions were performed by a single examiner. Left ventricular end-systolic and diastolic volumes were obtained using the modified Simpson method. Stroke volume (SV) was estimated by subtracting the left ventricular end-systolic volume from the left ventricular end-diastolic volume.

Each subject was then placed in the supine position. A standard four-lead ECG was attached, and a stethoscope was placed on the second right sternal border. Four blood pressure cuffs were placed around the arms and ankles. The subjects’ ECG, phonocardiogram, brachial arterial pulse waves, and tibial arterial pulse waves were simultaneously recorded using the vascular screening system, VaSera 1000/1500 (Fukuda Denshi Co. Ltd, Tokyo, Japan). Pre-ejection period (PEP), ejection time (ET), systolic blood pressure (SBP), and diastolic blood pressure (DBP) were automatically recorded by the device. ET was defined as the time difference between the upstroke and the dicrotic notch of the right brachial pulse wave. PEP was obtained by subtracting ET from the time between the Q wave and the second heart sound. SBP and DBP were determined by cuff sphygmomanometry. End-systolic pressure (Pes) was calculated from SBP and DBP using the formula published by Kappus et al³:

Pes = (0.205×SBP) + (0.898×DBP) + 0.4214. (1)

Then, ventricular-arterial coupling (the ratio of end-systolic elastance to arterial elastance) was calculated using the values of PEP, ET, Pes and DBP, as described previously [8]. Briefly, we solved the following simultaneous equations using Newton’s method and estimated Ees/Ea.

Ees/Ea = Pd/Pes (1 + k × ET/PEP) – 1 (2)

k = 0.53 (Ees/Ea)^0.51 (3)

In the above equations, k is the slope ratio of two straight lines in the ventricular time-varying elastance curve, one for the isovolumic phase and the other for the ejection phase. Eq. (2) is algebraically expressed using the concept of the left ventricular pressure-volume relationship. Eq. (3) is the empirical relationship between Ees/Ea and k, which was determined by extensively altering heart rate, contractility and afterload. DBP was used instead of Pd for the calculations.

Left ventricular end-systolic elastance (Ees) is defined by the following equation,

Ees = Pes / (Ved – SV – Vo) (4)

Where Vo is the volume at a Pes of 0 mmHg. It was assumed that Vo is equal to 0 ml in this study. Arterial elastance is defined as follows,

Ea = Pes / SV (5)

Solving equations (4) and (5) enables Ved (Ved calc) to be estimated from SV and Ea/Ees.

Ved calc = SV (1 + Ea/Ees) (6) ( Fig. 1)

Statistical analysis

JMP13 was used for the analysis. Continuous variables are reported as average and standard deviation (SD) values, and categorical variables are reported as proportions. Simple linear regression was used to compare Ved echo and Ved calc. Then Bland-Altman analysis was used to assess agreement between the two. The bias (the mean difference between Ved echo and Ved calc), limits of agreement, and percentage error (PE) were calculated. The percentage error was calculated using the formula, PE = 2 SD of bias/mean value of the reference method. The agreement between Ved calc and Ved echo was interpreted as clinically acceptable when the PE was 30% or less. A p-value less than 0.05 was considered significant.

The study included 58 healthy adults. Of them, adults with missing data or SV of ≥ 140 ml were excluded and the analysis was done with the remaining 47 patients. Patients’ background characteristics are shown in Table 1. The subjects were 39 men and 8 women, with a mean age of 24 ± 4 years, mean height of 169 ± 7 cm, and mean weight of 65 ± 12 kg. Ved echo was 91 ± 16 ml, and Ved calc was 102 ± 21 ml. There was a significant correlation between Ved echo and Ved calc (R² = 0.88, p < 0.01) (Fig. 2A). Bias and the limits of agreement were − 11.2 ml (-36.6; +14.2 ml ) (Fig. 2B). The percentage error for Ved calc was 27.7%.

In this study, Ved was determined from V-A coupling (Ees/Ea) measured non-invasively, and whether it could be used as a substitute for Ved measured by echocardiography was investigated. The results showed a significant correlation and compatibility between the two, and it was concluded that Ved from Ees/Ea could be used as a substitute.

Cardiac afterload, such as the involvement of sympathetic nerves from surgical invasion or stimulation, or increased total peripheral vascular resistance, exerts a large effect on blood pressure fluctuations in whole-body management during surgical anesthesia and in the area of intensive care. However, the effect of cardiac preload, such as direct involvement of capacitance vessels or bleeding, is also important. Ved is a direct measure of cardiac preload. However, the direct measurement of Ved is highly invasive.⁴ Ved can be directly measured with techniques such as cardiac computed tomography, real-time three-dimensional transesophageal echocardiography, or cardiac magnetic resonance imaging,⁵ but these techniques cannot be used on patients intraoperatively and, depending on the measurement method, can hardly be called noninvasive. Today, stroke volume variation (SVV) and global end-diastolic volume have been commercialized as techniques to monitor cardiac preload,^6,7 but a more direct and less invasive method would be preferable. Clinical monitoring for the noninvasive and continuous assessment of Ved does not currently exist. Therefore, a method for noninvasive and continuous monitoring of Ved was devised.

The PEP and ET used in the present study could be noninvasively measured using a vascular screening system (VaSera VS-1000, Fukuda Denshi Co., Ltd, Tokyo, Japan). They can be measured using an oscillometric method with cuffs around both upper arms and both legs. Systolic blood pressure (Ps) and diastolic blood pressure (Pd) are also displayed. In addition, according to the study of Kappus et al., a substitution equation that uses Ps and Pd can be used for Ped.³

Further study is needed to compare the utility of the Ved from the present method and SVV based on invasive arterial pressure waveform analysis. However, though with SVV the effects on SV of fluctuations in intrathoracic pressure from artificial respiration are quantified and monitored, the present method is an index that is unrelated to artificial respiration and so will have widespread clinical applications; for example, it can be used even in patients who are awake during intensive care.

SV measured with transthoracic ultrasonography was used in this study. However, in the future, it will be possible to measure Ved continuously by using a method that predicts SV noninvasively from estimated continuous cardiac output.⁸

Study limitations

The present study has several limitations. First, V₀ was assumed to be zero with the present method. Since the actual value is V₀ plus a calculated value, the calculated value should theoretically be smaller than the actual value, and, especially in patients whose V₀ is significantly large, such as in those with dilated cardiomyopathy, it is thought that the calculated value will be underestimated with respect to the actual value.

Second, the subjects in the present study were young, healthy people with normal cardiac function. In a past report,⁹ Ved in Japanese persons in their 20s and 30s was about 100 ml, and so in the present study, subjects with Ved ≥ 140 ml were excluded. In the future, it will be necessary to investigate whether there is a similar correlation and compatibility between Ved echo and Ved calc in patients with Ved ≥ 140 ml and patients with decreased cardiac function.

Third, the subjects in the present study were not intubated and had spontaneous respiration. Whether there is also a similar correlation and compatibility between Ved echo and Ved calc in patients under general anesthesia and those who are intubated will need to be investigated.

The findings of the present study suggest that left ventricular end-diastolic volume can be monitored noninvasively and continuously using ventricular-arterial coupling.

a) Ethics approval and consent to participate

The study protocol was approved by the Research Ethics Committee of the University of Fukui Hospital (No.20140125). The authors obtained informed consent for participate for this study from the patients.

b) Consent for publication

Not applicable

c) Availability of data and materials

The datasets used and/or analysed during the current study available from the corresponding author on reasonable request.

d) Competing interests

Not applicable

e) Funding

This research was supported by the Japan Agency for Medical Research and Development (AMED) under Grant Number JP22hk0102081.

f) Authors' contributions

M.H.: conception and design, drafting of the manuscript; Y.M.: acquisition and data, analysis and interpretation of data, statistical analysis; S.K.: analysis and interpretation of data, K.S.(Kenji Shigemi): conception and design, critical revision of the manuscript for important intellectual content. All authors participated in preparation of the manuscript, and all approved the final version.

g) Acknowledgements

Not applicable

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Table 1 is available in the Supplementary Files section.

No competing interests reported.

Table1.jpg
Table 1. Demographic characteristics and blood pressure of the subjects BMI: body mass index, SBP: systolic blood pressure, DBP: diastolic blood pressure, PEP: pre-ejection period, ET: ejection time Data are presented as mean ± standard deviation, except where otherwise indicated.

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Journal Publication

published 28 Apr, 2023

Read the published version in BMC Anesthesiology →

Editorial decision: Major revision
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Reviewers agreed at journal
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You are reading this latest preprint version

Estimation of left ventricular end-diastolic volume by left ventricular arterial coupling and stroke volume: A prospective, observational study

Status:

Journal Publication

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Abstract

Background

Methods

Results

Conclusions

Figures

Background

Methods

Study population

Measurements

Statistical analysis

Results

Discussion

Study limitations

Conclusions

Declarations

References

table

Additional Declarations

Supplementary Files

Status:

Journal Publication

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