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DR FAITH J ROSS (Orcid ID : 0000-0001-8088-0148)
DR GREGORY J LATHAM (Orcid ID : 0000-0002-1440-9742)
Article type : Research Report
Handling Section Editor : Dr Chandra Ramamoorthy
Assessment of Muscle Oxygenation in Children with Congenital Heart Disease
Running head: Muscle Oximetry in Congenital Heart Disease
1. Faith J. Ross1
2. Lorilee S. L. Arakaki2
3. Wayne A. Ciesielski2
4. D. Michael McMullan3
5. Michael J. Richards1
6. Jeremy Geiduschek1
7. Gregory Latham1
8. Vincent Hsieh1
9. Kenneth A. Schenkman1,2
1 Department of Anesthesiology and Pain Medicine, Seattle Children’s Hospital, University of
Washington, Seattle, USA
2 Department of Pediatrics, University of Washington, Seattle, USA
3 Department of Cardiothoracic Surgery, Seattle Children’s Hospital, University of Washington,
Seattle, USA
Corresponding Author:
Dr. F. Ross. *ORCID 0000-0001-8088-0148* Department of Anesthesiology and Pain Medicine,
Seattle Children’s Hospital, University of Washington, 4800 Sandpoint Way NE Seattle, WA 98105,
USA; faith.ross@seattlechildrens.org
What is already known: Prior studies have suggested that adaptive responses to congenital heart
disease result in abnormal muscle metabolism in affected children.
What this article adds: This study demonstrates that muscle oxygenation is abnormal in children with
both cyanotic and acyanotic CHD and suggests that noninvasive monitoring of muscle oxygenation
may provide valuable information in situations where children with heart disease are at risk of
hemodynamic compromise.
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Abstract
Background
Adaptive responses to congenital heart disease (CHD) result in altered muscle perfusion and
muscle metabolism. Such changes may be detectable using noninvasive spectroscopic monitors.
Aim
In this study we aimed to determine if resting muscle oxygen saturation (MOx) is lower in
children with acyanotic or cyanotic CHD than in healthy children and to identify differences in muscle
oxygen consumption in children with cyanotic and acyanotic CHD.
Methods
Using a custom fiber optic spectrometer system, optical measurements were obtained from
the calf or forearm of 49 patients (17 with acyanotic CHD, 18 with cyanotic CHD, and 14 control). 20
additional control patients were used to develop the analytic model. Spectra were used to determine
MOx at baseline, during arterial occlusion, and during reperfusion. The rate of muscle desaturation
during arterial occlusion was also evaluated. Two-sample t-tests were used to compare each heart
disease group with the controls.
Results
Patients with acyanotic and cyanotic CHD had lower baseline MOx than controls. Baseline
MOx was 91.3% (CI 85.9, 96.7%) for acyanotic patients, 91.1% (CI 86.3,95.9%) for cyanotic patients,
and 98.9% (CI 96.7,101.1%) for controls. Similarly, MOx was lower in the acyanotic and cyanotic
groups than the controls after reperfusion (84.6% (CI 74.1, 95.1%) and 82.1% (CI 74.5,89.7%) vs.
98.9% (96.5,101.3%)). The rate of decline in oxygenation was significantly greater in cyanotic patients
vs. controls (0.46%/s (CI 0.30,0.62%/s) vs 0.17%/s (0.13,0.21%/s).
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Conclusion
This study demonstrates that muscle oxygenation is abnormal in children with both cyanotic
and acyanotic CHD. This suggests that noninvasive monitoring of muscle oxygenation may provide
valuable information in situations where children with CHD may be at risk of hemodynamic
compromise.
Keywords
muscle, oximetry, cyanotic, heart disease, child, congenital
Introduction
Congenital heart disease (CHD) occurs in approximately one out of every 100 infants, and
one quarter of these infants have cyanosis due to some fraction of deoxygenated blood bypassing the
lungs and entering the systemic circulation. Although most infants with cyanotic congenital heart
disease (CCHD) eventually require palliative or corrective surgery, they often tolerate cyanosis
relatively well. Various compensatory mechanisms help deliver oxygen to tissues and organs in these
patients, and indeed many people live into adulthood with persistent cyanosis.
Studies of the bioenergetics of patients with chronic hypoxemia are limited, but some
evidence in children with cyanotic heart disease suggests that there are metabolic differences in the
muscles of these children compared with healthy subjects. In an MRI study of muscle bioenergetics,
Miall-Allen et al noted that energy reserves were depleted more rapidly in children with CCHD
compared with controls.1 Adatia et al demonstrated decreased muscle oxidative ATP synthesis in
cyanotic patients and suggested that this was due to reduced oxygen delivery to muscle in chronic
hypoxemia.2 Basal metabolism in adults with CCHD has not been shown to vary significantly
compared with healthy control subjects, although higher venous lactate has been measured,
suggesting that more anaerobic metabolism occurs than might be expected.3
In the heart, remodeling of the coronary vasculature is seen in adult patients with CCHD, and
increased angiogenic gene expression has been demonstrated in the myocardium of children with
tetralogy of fallot.4,5 Han et al demonstrated increased levels of vasodilatory nitric oxide metabolites in
the blood of patients with CHD.6 Thus, vasodilation and angiogenesis appear to play a role in
enhancing oxygen delivery to the myocardium and perhaps the peripheral tissues in patients with
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chronic cyanosis. How well these adaptive responses to chronic hypoxia normalize cellular oxygen
levels and metabolism is not known. Better understanding of the basic metabolic adaptations to
chronic hypoxia, as seen in children with CCHD, is crucial to developing optimal monitoring and
treatment strategies for these vulnerable patients.
Many of the prior investigations into muscle bioenergetics have relied on invasive
measurements or MRI. However, it is possible to obtain valuable information about muscle physiology
using bedside, noninvasive muscle oximetry to evaluate the oxygen saturation of hemoglobin and
myoglobin in muscle cells. The metabolic rate of muscle tissue can be determined by measuring the
rate of change in muscle oxygen saturation (MOx) during a disruption of blood supply to the tissue.
The pre-occlusion steady-state oxygen consumption of muscle is related to the change in MOx
measured during the first few minutes of occlusion of the arterial supply to a muscle.14
We have developed at our institution a noninvasive monitor that allows us to determine
absolute values of MOx by exploiting the optical differences between the oxygenated and
deoxygenated forms of both hemoglobin and myoglobin in the visible and near-infrared spectral
regions. In this study we used muscle oximetry to determine if resting muscle oxygen saturation is
lower in children with acyanotic or cyanotic CHD than in healthy children and to identify differences in
muscle oxygen consumption in children with cyanotic and acyanotic CHD.
Materials and Methods
Patient Population
The study was approved by the Institutional Review Board at the University of Washington.
Informed consent was obtained from parents prior to participation. We enrolled children with cyanotic
CHD and acyanotic CHD. CHD patients with baseline arterial oxygen saturation (SaO2 by pulse
oximetry) less than 90% and with lesions typically associated with cyanosis were considered to be
cyanotic. Lesions in this group included various forms of single ventricle heart disease and
transposition of the great arteries prior to the arterial switch. Cyanosis in all cases was due to
circulatory mixing, and no patients had clinically significant pulmonary disease to account for their
cyanosis. Patients with CHD were recruited on presentation for cardiac surgery or cardiac
catheterization. The mean age was 10.6 mo (SD ± 13.5 mo) in the acyanotic group and 8.2 mo (SD ±
11.5 mo) in the cyanotic group. (Table 1)
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Control patients were without cardiovascular disease and were recruited from the population
undergoing reconstructive craniofacial surgery, urologic surgery, or minor general surgery procedures.
Any patients with known peripheral arterial or venous thrombosis or other contraindication to
tourniquet placement were excluded. The mean age in the control group was 9.6 mo (SD ± 5.2 mo).
Patient Protocol
An optical probe was placed on the surface of the skin over the muscles on the back of the
lower leg or ventral forearm and affixed with Coban or tape. In CHD patients, optical spectra at
baseline were obtained for 5 min with the patient breathing 100% oxygen only if determined to be safe
by the attending anesthesiologist. All but 2 patients in the cyanotic group and 3 patients in the
acyanotic group were placed on 100% oxygen for baseline measurements. A blood pressure cuff was
then inflated on the proximal leg or upper arm to a pressure of 150 mmHg or 50 mmHg above the
systolic blood pressure (whichever was higher) and maintained for 3 min. After inflation of the blood
pressure cuff, the fraction of inspired oxygen (FiO2) was adjusted at the discretion of the
anesthesiologist. Recording of optical spectra continued for 5 min after release of the tourniquet.
Spectra were acquired every 3-5 seconds throughout the protocol.
In control patients with normal cardiopulmonary physiology, the same protocol was used,
except that the blood pressure cuff was inflated for 15 min. The purpose of the long cuff inflation was
to fully deplete oxygen in the muscle tissue in the proximal leg or arm for use in developing an
analytic model. All patients in the control group were placed on 100% oxygen for 5 min before the
start of cuff ischemia.
MOx Measurements
Optical spectra were acquired from the visible and near-infrared (NIR) spectral regions (500-
800 nm) with an optical system consisting of a custom-designed fiber optic probe, a custom-designed
LED-based light source, and an imaging spectrometer previously described.15
We used optical probes with distances from the illuminating to the detecting optical fibers
ranging from 10 to 15 mm. The choice of probe was based on the size and adiposity of the patient
and the resulting quality of optical spectra obtained on initial testing of each patient. Ultrasound
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imaging was done on some of the patients to measure the distance to the muscle layer under the
probe. In the leg, the distance to the muscle layer varied between 4 and 6 mm.
MOx was determined by analysis of the spectra using a multi-wavelength analytical approach
previously described.11 The pattern-matching algorithm, locally-weighted regression (LWR), was
trained on a reference set of 811 spectra obtained from 20 craniofacial surgery patients that had no
overlap with the control group.
For the CHD patients and the study control patients, a MOx value was obtained from each
acquired spectrum by applying the spectrum to the LWR model. The Q-residuals test was used to
determine whether or not MOx measurements made from spectra acquired from CHD and control
patients in this study were valid. The Q-residual test is an accepted chemometric test that determines
if there is sufficient similarity in character between the given spectra and those in a training set that
were used to build an analytical model.17 Patients with Q-residuals higher than the 95% confidence
interval of the Q-residuals in the training set were excluded from the study because their MOx
readings were not considered valid.
Data analysis
Baseline mean MOx values were calculated for each CHD or control patient over the 4 min
immediately preceding the inflation of the blood pressure cuff. The rate of decrease in MOx upon
inflation of the cuff was determined by a linear fit to the MOx values in the first 60 sec after inflation of
the cuff. Two-sample t-tests were done on baseline and recovery MOx values and slopes that
compared acyanotic and cyanotic groups to the control group. P-values less than 0.05 were
considered significant.
Results
Validation of LWR model
The LWR model with the minimum error during cross-validation had 1 latent variable, 2
principal components, and 100 selected samples. The root-mean-square error of cross-validation
(RMSECV) for this model was 8.3%. The subjects in the calibration set displayed Hotelling’s T2 and Q
residuals that indicated there were no unusual subjects or samples in the calibration set.
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In order to validate the model, MOx measurements were made from 14 control subjects that
were not included in the model. The LWR model produced accurate MOx measurements compared to
Multivariate Curve Resolution (MCR) estimates of MOx obtained from each subject’s data set. The
root-mean-square error (RMSE) for all 583 spectra was 6.5%.
Patient characteristics
For the control group, consent was obtained from 81 healthy patients. The reasons for
exclusion from being in the LWR training set or the study control group are indicated in Fig. 1. Six
patients underwent an anomalous protocol due to operator error and the system malfunctioned during
the study of one patient. Unusable spectra were found in six patients due to poor signal quality in the
visible region of the spectra. Another 32 patients were excluded because they did not display
complete desaturation during the 15 min of blood pressure cuff inflation. The first 20 patients who
were not excluded for any reason comprised the training set. Subsequent patients who were not
excluded for any reason, including high Q-residuals (n = 2) comprised the study control group (n =
14).
For the cardiac groups, we obtained consent from 51 patients with CHD. As shown in Fig. 1,
two patients were excluded from the data analysis because of an incomplete protocol due to operator
error and 14 had high Q-residuals. Of the 35 patients included in the study, 18 were cyanotic and 17
were acyanotic.
Patient characteristics are shown in Table 1. There were more males in the control and
cyanotic groups than in the acyanotic group (71% and 67% vs 41%). Baseline oxygenation saturation
(measured prior to surgery on room air) was 99.4 ±0.6% in the control group, 99.5 ±0.9% in the
acyanotic CHD group, and 83.6±7.3% in the cyanotic CHD group.
Muscle oxygenation
Fig. 2 shows the time course of MOx for two representative patients (one from the acyanotic
group, and one from the cyanotic group) through the full sequence of measurements. In cyanotic
patients, MOx decreased to a greater extent during the 3-minute ischemia period than in acyanotic
patients.
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The aggregate data for each group, including baseline MOx, slope of decline in MOx over the
first minute of ischemia, MOx after 3 minutes of ischemia, and recovery MOx are shown in Table 2.
Fig. 3 shows that baseline MOx was significantly lower in the acyanotic and cyanotic CHD patients
than in controls (91.3% (CI 85.9, 96.7%) and 91.1% (CI 86.3,95.9%) vs 98.9% (CI 96.7,101.1%)
respectively).
(Note that muscle oxygen saturation can exceed arterial saturation at baseline because myoglobin,
with a higher affinity for oxygen than hemoglobin, remains fully saturated at a much lower PaO2.)
Similarly, MOx during the recovery phase was significantly lower in the acyanotic and cyanotic CHD
patients compared to controls (84.6% (CI 74.1, 95.1%) and 82.1% (CI 74.5,89.7%) vs. 98.9%
(96.5,101.3%)). The patients without CHD achieved full return of muscle oxygenation to baseline after
4 min of reperfusion. Muscle saturation in the acyanotic and cyanotic groups did not reach baseline
after 4 min of reperfusion despite the shorter tourniquet occlusion in these groups. As we did not
continue monitoring to full muscle oxygen recovery in the CHD groups we cannot comment further on
the recovery time frame in these patients.
In Fig. 4A, the slope of decline in MOx over the first minute of occlusion was significantly
steeper in the cyanotic patients than controls (0.46%/s (CI 0.30,0.62%/s) vs 0.17%/s (0.13,0.21%/s)).
The slope of decline in MOx over the first minute for acyanotic patients (0.21%/s (CI 0.09,0.33%/s))
was not significantly different from controls. When comparing cyanotic versus acyanotic CHD patients,
cyanotic patients reached a significantly lower MOx at the end of 3 min of ischemia (Table 2).
Discussion
In this study we sought to answer two main questions: Do adaptive mechanisms in patients
with CHD provide for normal oxygenation in peripheral muscle? Are there differences in oxygen
metabolism in patients with CHD that can be detected with a noninvasive monitor? Our data suggest
that adaptive responses in children with acyanotic and cyanotic CHD are inadequate to provide for
normal MOx at baseline and that oxygen is more rapidly depleted during ischemia in children with
cyanotic CHD than in healthy controls.
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In order to fully appreciate these findings, it is important to understand how the device used in
this study differs from traditional near-infrared spectroscopy (NIRS) devices. There are several
previous studies utilizing NIRS to investigate muscle oxygenation.7,8 Most NIRS measurements made
from muscle are based on analyses of 2 to 4 discrete wavelengths of light within the range of 660-850
nm.9 A major limitation of these traditional NIRS measurements is the inability to distinguish optical
signals from hemoglobin and myoglobin, two oxygen binding proteins that reside in distinct anatomic
compartments in the body. Thus, most studies of muscle oxygenation report a combined hemoglobin
and myoglobin saturation value. There has been some dispute about the relative contributions of
hemoglobin and myoglobin to these signals, leading some investigators to ignore the myoglobin
contribution completely. However, previous work from our group has demonstrated a significant
contribution of myoglobin to the overall optical signal.10 We have also shown in the past that using a
multiwavelength analytic approach with spectral information from the visible and NIR regions allows
for improved muscle oxygen measurements over traditional discrete wavelength approaches.11
From a clinical perspective, existing NIRS devices typically assume a fixed distribution
between venous and arterial blood (a 70:30 ratio); however, this fixed ratio does not account for
known physiologic variations in blood volume between these compartments, especially under
pathologic conditions.12 Thus, this approach only allows for determination of a relative value of oxygen
saturation; it is not absolute. Our approach, presented in this manuscript, intentionally includes
analysis of contributions from both myoglobin and hemoglobin saturation to more accurately reflect
total muscle oxygenation in the volume of tissue sampled. By virtue of analyzing an entire wavelength
region, we calculate an absolute saturation value, allowing for more meaningful comparison between
subjects. Myoglobin constitutes about 80% of the oxygen carrying capacity in resting skeletal muscle
and is a major contributor to the signal.13
Hemoglobin and myoglobin have large absorbances in the visible wavelength region
compared to the NIR region. Even so, sensitive detectors such as the CCD camera in our system
(Synapse, Horiba Jobin Yvon) can accurately measure low photon counts. We have previously
investigated the depth of penetration of photons in the visible and NIR regions in phantoms containing
solutions of hemoglobin and a scatterer.16 We found that at biological hemoglobin concentrations, the
most probable photon path depths in the visible region were similar to, and at most 1 mm shallower,
than those in the NIR.
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We have demonstrated low baseline MOx in children with acyanotic CHD and cyanotic CHD
despite a normal arterial oxygen saturation in the former group (Figure 3). We postulate that reduced
skeletal muscle blood flow in the setting of maintained oxygen consumption results in decreased
myoglobin saturation and increased arterial-venous oxygen difference with more exaggerated venous
desaturation. The effect seems to be similar for both cyanotic and acyanotic children. While changes
in muscle blood flow have not been well-established in children, studies in adults with Fontan
circulation demonstrate reduced muscle mass and diminished flow-mediated vasodilation in
peripheral arteries.20,21,23 Thus, reduced muscle blood flow appears to be a plausible explanation for
the baseline muscle deoxygenation demonstrated in this study.
In regard to the question about oxygen metabolism, we found the muscle of children with
acyanotic CHD deoxygenated at a rate similar to control patients, whereas patients with cyanotic CHD
deoxygenated more rapidly (Figure 4). In healthy patients, the rate of deoxygenation after tourniquet
occlusion is an indication of the metabolic rate of muscle at the time of occlusion.14 If we were to apply
this logic to our groups, it would appear that the cyanotic patients had the most rapid rate of
metabolism and that the metabolism of acyanotic patients was similar to controls. However, this
assumes that oxygen supply to the muscles is not a limiting factor and is similar between groups. This
seems unlikely to be the case, so an alternative explanation must be entertained. The oxygen content
in peripheral muscles depends on the amount of oxygen bound to hemoglobin and myoglobin as well
as dissolved oxygen. We have demonstrated that the saturation of oxygen in hemoglobin and
myoglobin is lower for children with both cyanotic and acyanotic heart disease. We would expect
further differences in oxygen content between cyanotic and acyanotic children in the setting of
administration of 100% oxygen because differences in dissolved oxygen will also come into play.
Right to left shunting in cyanotic patients limits the possible increase in oxygen delivery upon
administration of 100% oxygen, proportional to the fraction of systemic cardiac output that has
bypassed the lungs. Assuming a similar muscle metabolic rate, when arterial inflow to the muscle is
interrupted, oxygen continues to be extracted from the arterial blood remaining in the muscle,
resulting in diminishing muscle oxygenation over time. Because hemoglobin in arterial blood is less
saturated with oxygen and contains less dissolved oxygen at baseline in cyanotic patients, muscle
desaturation is more rapid in this group and MOx reached a lower nadir than acyanotic or control
patients after 3 min of ischemia.
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We also found impaired reperfusion after a period of induced muscle ischemia via arterial
occlusion in both CHD groups. Neither group recovered to their baseline level of muscle oxygenation
after 4 min of reperfusion (Fig. 3). The control group, on the other hand, did fully return to baseline
despite the fact that they underwent arterial occlusion for five times as long as the CHD groups. This
finding is consistent with our hypothesis that limited skeletal blood flow in children with CHD
contributes to diminished skeletal muscle oxygenation in situations of physiologic stress.
There are several potential limitations to this study. Because of the young age of the patients
being studied and the discomfort associated with arterial tourniquet placement, it was necessary to
study patients under general anesthesia. Both volatile anesthetics and muscle relaxants used in these
procedures have an impact on muscle cell contraction and alter muscle metabolic rate and the
distribution of cardiac output to muscle cells.24-26 However, because all of the patients in this study
were anesthetized, comparisons between groups should be valid regardless of potential confounding
effects of anesthesia.
A significant number of patients without CHD failed to reach full muscle deoxygenation during
the 15-minute arterial occlusion and were not included in the training set or the control group (Figure
1). Similar studies from our group using the first digital interosseous muscle in awake adult patients
have not had this issue.11,13 Potential reasons for this discrepancy include incomplete occlusion of
arterial inflow due to inadequate inflation pressure, geometric differences in tourniquet fit in young
infants, or the impact of anesthesia. It is also possible that the muscle layer in infants is deeper than
anticipated and the optical signal included some tissue overlying the muscle. The inclusion of fatty
tissue with a low metabolic rate would lead to falsely low measurements of muscle desaturation rate.
Ultrasound examination of the arms and legs of several of our patients suggested that the
interrogation depth of our sensor was adequate to evaluate muscle tissue.
Also, the fact that 2 cyanotic patients and 3 acyanotic patients were not placed on 100%
oxygen for baseline measurements prior to ischemia could potentially have impacted the results. A
sensitivity analysis of the data with these patients excluded from the analysis did not substantively
change the findings.
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Even with these limitations, the findings presented here make a compelling case for the utility
of muscle oximetry in evaluating patients with CHD. The impaired recovery in oxygenation in both
cyanotic and acyanotic groups and increased rate of desaturation in the cyanotic group suggest that
these patients are very susceptible to muscle ischemia in situations of hemodynamic stress. Although
the specific monitor used in this study is not commercially available, this study strongly suggests that
further clinical trials with real-time monitors of muscle saturation are warranted. Just as measurement
of cerebral oxygenation by near infrared spectroscopy has become a clinical standard of care in
pediatric heart surgery, muscle oximetry may in the future become a useful adjunct in detecting
hemodynamic perturbations that otherwise might not be appreciated by routine hemodynamic
monitoring.
Acknowledgements
We would like to thank Drs. Denise Joffe, Michael Eisses, and Kevin Conley for their insightful
contributions to discussions regarding the results.
Disclosures
1. This project was approved by the Institutional Review Board of the University of Washington.
2. Funding for this project was provided in part by grants from the National Institutes of Health
1R21GM107840, the American Heart Association 13GRNT13280002, and the University of
Washington Royalty Research and Faculty Research Support Funds.
3. Drs. Arakaki and Schenkman and Mr. Ciesielski have a significant financial interest in
Opticyte, Inc., which is not directly or significantly related to the research. The other authors
declare no conflicts of interest.
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2008;101(2):171-177.
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Tables
Table 1: Patient Characteristics
Control
(n = 14)
Acyanotic
(n = 17)
Cyanotic
(n = 18)
Age
9.6 ± 5.2 mo
10.6 ± 13.5 mo
8.2 ± 11.5 mo
Gender
M 10 (71%)
F 4 (29%)
M 7 (41%)
F 10 (59%)
M 12 (67%)
F 6 (33%)
Preop SpO2
99.4 ± 0.6%
99.5 ± 0.9%
83.6 ± 7.3%
Surgical procedure
Facial plastic 7 (50%)
Urology 4 (29%)
Other 3 (21%)
TOF repair 5 (29%)
ASD repair 3 (18%)
Arch repair 3 (18%)
AVSD repair 2 (12%)
VSD repair 2 (12%)
Other 2 (12%)
BD Glenn 4 (22%)
Norwood 3 (17%)
Fontan 3 (17%)
Arterial Switch 3 (17%)
Other 5 (28%)
Continuous variables are summarized with mean ± SD and categorical variables with N (%).
Table 2. Muscle Oxygenation (MOx) in Controls and Patients with Congenital Heart Disease
* P value comparing cardiac group versus controls
# P value comparing cyanotic group to acyanotic group
Controls
(n = 14)
Acyanotic
(n = 17)
Cyanotic
(n = 18)
Mean
95% CI
Mean
95% CI
P
Mean
95% CI
P
Baseline MOx (%)
98.9
96.7,101.1
91.3
85.9 96.7
0.011*
91.1
86.3,95.9
0.005*
Recovery MOx (%)
98.9
96.5, 101.3
84.6
74.1, 95.1
0.012*
82.1
74.5, 89.7
0.0002*
1-min Slope (%/s)
0.17
0.13, 0.21
0.21
0.09, 0.33
0.52*
0.46
0.30, 0.62
0.001*
MOx at end of 3-min
of ischemia (%)
56.4
38.5, 74.3
31.4
13.1, 49.7
0.047#
Accepted Article
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Figure Captions
Figure 1: Enrollment diagram of study populations and reasons for exclusion.
Figure 2: Example of muscle oxygenation at baseline, during arterial occlusion, and recovery for
representative cyanotic and acyanotic patients.
Figure 3: Muscle oxygenation at baseline and during recovery from arterial occlusion in children with
cyanotic and acyanotic heart disease vs controls.
Figure 4: Slope of deoxygenation during the first minute after arterial occlusion in cyanotic and
acyanotic patients vs controls.
Accepted Article
This article is protected by copyright. All rights reserved.
Accepted Article
This article is protected by copyright. All rights reserved.
