Download Cardiac Output and Index in Obese and Non

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Radiol
and2005;8:226-232
Obesity: SPECT MIBI
ORIGINAL ARTICLE
Cardiac Output and Index in Obese and Non-obese Patients
using Gated Single Photon Emission Computed Tomography
Sestamibi Perfusion Imaging
JP Coffey, JC Hill
Department of Nuclear Medicine, Lancashire Teaching Hospitals NHS Trust,
Royal Preston Hospital, Preston, United Kingdom
ABSTRACT
Objective: To assess prospectively the overall prevalence of abnormal cardiac index values in a symptomatic
group of patients from gated single photon emission computed tomography perfusion studies and to compare
cardiac index of patients with body mass index <30 and obese patients (body mass index >30).
Patients and Methods: 112 patients (62 females) aged 37 to 81 years (mean, 57 years) referred for evaluation
of chest pain, dyspnoea or inconclusive exercise electrocardiogram, underwent gated single photon emission
computed tomography perfusion imaging with technetium 99m sestamibi intravenously following Bruce exercise protocol (102 patients) or dobutamine stressing (10 patients). Cardiac output was calculated as the product of resting heart rate and stroke volume and cardiac index determined using the body mass index. Left
ventricular ejection fraction, stroke volume, and end-systolic volume were determined for each patient.
Results: Seventy three patients (65%) had an abnormal cardiac index (<2.5 L/min/m2). The mean cardiac index
overall was 2.19 L/min/m2. Twelve patients had left ventricular ejection fraction less than 50%, and the mean
left ventricular ejection fraction overall was 61%. Thirty two patients with body mass index >30 had mean
cardiac index of 2.28 L/min/m2, which was not significantly different from an age-matched group of 32 nonobese controls (body mass index <30; mean cardiac index, 2.24 L/min/m2). Left ventricular ejection fraction
was elevated in the obese group compared with the non-obese group (mean, 65.2% versus 58%; p < 0.03).
Conclusions: A high prevalence of abnormally low cardiac index was observed in symptomatic patients. Obese
patients had similar cardiac index to non-obese control patients, but had an elevated left ventricular ejection
fraction suggesting hypersystolic function.
Key Words: Obesity, Cardiac output, Technetium Tc99m sestamibi, Tomography, emission-computed, single-photon,
Tomography, X-ray computed, Ventricular dysfunction, left
INTRODUCTION
Cardiac output (CO) has been recognised as the most
important measurement in the assessment of cardiac
pump function and overall haemodynamic function.1,2
CO normalised to body surface area (BSA) as cardiac
index (CI) readily enables comparison of haemodynamic function, independently of body mass, between
patients.
Correspondence: Dr. JP Coffey, Department of Nuclear Medicine,
Lancashire Teaching Hospitals NHS Trust, Fulwood, Preston, PR2
1HT, United Kingdom.
Tel: (44 1772) 523 747 ; Fax: (44 1772) 523 721;
E-mail: [email protected]
Submitted: 20 February 2006; Accepted: 19 September 2006.
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Gated single photon emission computed tomography
(SPECT) imaging permits automated calculation of enddiastolic volume, end-systolic volume, stroke volume
(SV) and left ventricular ejection fraction (LVEF). Strong
correlations between the values of volumetric data acquired by this imaging modality and those from echocardiography, gated blood pool scanning and magnetic
resonance imaging have been consistently reported in
the literature,3,4 with overall correlation coefficients ranging up to 0.9.5,6 To date, the use of gated SPECT perfusion
imaging has not been reported in the measurement of
CO/CI in the clinical setting with differing patient groups.
Obesity is well-recognised as an influence on cardiovascular morbidity and mortality; clinical and autopsy
© 2005 Hong
College2005;8:226-232
of Radiologists
J HKKong
Coll Radiol
JP Coffey, JC Hill
studies have confirmed the pathological entity of obese
cardiomyopathy, characterised by volume overload and
hyperdynamic circulation, leading frequently to congestive cardiac failure. Relations between structural cardiac anomalies, systolic function and morbid obesity
have been confirmed by echocardiography, cardiac catheterisation and necropsy.7-9 These correlations are also
evident even in mild obesity.10,11 Obesity is associated
with haemodynamic overload with increased blood
volume, elevated SV12 and increased CO, owing in part
to increased lean body mass.13,14 Hypersystolic function
at rest has been reported in obesity,7 but in response to
exercise, the expected LVEF increase is impaired in
obese patients.15
Gated SPECT perfusion imaging of left ventricular function of obese patients is less operator-dependent and
volumetric data acquisition is likely to be less restricted
by patient body habitus than with echocardiography.
This two-part observational study firstly evaluated,
prospectively, the overall prevalence of reduced CO and
CI in a cohort of symptomatic patients referred in an
outpatient setting for technetium 99m sestamibi (MIBI)
SPECT cardiac perfusion imaging. The second part of
the study compared CI of obese patients with an agematched group of non-obese patients, thereby assessing the relative haemodynamic function of both of the
groups.
PATIENTS AND METHODS
112 patients (62 females), aged 37 to 81 years (mean, 57
years) referred for evaluation of symptoms (dyspnoea,
reduced exercise tolerance, chest pain whether typical
or atypical of cardiac origin) by myocardial stress
perfusion imaging were studied prospectively in an outpatient setting. Body mass index (BMI) was calculated
for each patient and BSA determined using the Mosteller
(modified Dubois) method. 450 MBq of technetium 99m
MIBI was injected intravenously following exercise
using the Bruce treadmill protocol. 10 patients underwent pharmacological stressing using dobutamine.
Beta-blocker therapy was stopped at least 24 hours before the stress testing. Gated SPECT perfusion imaging
was performed 45 minutes later using 64 x 64 matrix,
cardiac cycle divided into 8 equal intervals, filtered
backprojection and data sets reconstructed using Quantitative Gated SPECT (QGS; Cedars Sinai, Los Angeles,
CA, USA) software. Satisfactory time volumetric curves
for ventricular filling were obtained for each patient
together with readings for LVEF, SV, end-diastolic
J HK Coll Radiol 2005;8:226-232
volume and end-systolic volume. Three values for
resting heart rate (HR) were taken and the mean
recorded, with the patient supine during the scanning
interval of typically 20 to 30 minutes. CO was calculated as the product of HR and SV and the CI determined accordingly.
In our institution, in accordance with accepted practice
for limiting administered radiation dose, only those patients with perfusion anomalies identified on the initial
post-stress study receive a resting gated MIBI scan for
corroboration. Consequently, in order to eliminate a
selection bias against patients with normal post-stress
perfusion images, only the post-stress gated images,
which were acquired for all patients, were used in this
volumetric study. Prognostic information incremental
to that obtained perfusion and pretest data is also supplied by LVEF and systolic volumetric measurements
from post-stress gated SPECT imaging.16
SV, LVEF and CO values from both post-stress and later
resting gated studies were, however, compared in 32
patients who had perfusion anomalies identified on the
initial post-stress scan. This was done to preclude any
possibility of myocardial stunning influencing the
volumetric and CO readings of the post-stress studies.
RESULTS
Seventy three patients (65%) had an abnormal CI,
defined as <2.5 L/min/m2 (mean ± standard deviation
[SD] CI, 2.19 ± 0.51) with only 12 patients having LVEF
less than 50% (mean ± SD LVEF, 61 ± 15.4). Thirty
two patients (28%) had perfusion abnormalities of 1 to
5 cardiac segments and/or 1 to 3 fixed perfusion defects consistent with possible infarcted segments. Of this
group, 25 patients had an abnormal CI (<2.5 L/min/m2).
However, angiographic correlation of the perfusion
anomalies was not available and as a result the clinical
significance of these perfusion anomalies is uncertain.
These 32 patients underwent further imaging with a
resting MIBI gated SPECT study. t-tests (two sample
test of means) revealed no significant differences
between resting and post-stress SV and LVEF in this
group. A typical volumetric data screen is shown in
Figure 1.
Thirty two patients with BMI >30 kg/m2 (mean BMI,
35.7) had a mean CI of 2.28 L/min/m2 and were compared with an age-matched group of 32 patients with
BMI <30 (mean, 26) with mean CI of 2.24 L/min/m2.
Similarly, CO was significantly increased in the obese
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Cardiac Index and Obesity: SPECT MIBI
Figure 1. Typical volumetric data screenshot (normal-shaped time volumetric curve). The patient was a 42-year-old morbidly obese
female with body mass index 57.4, cardiac output 7.2 L/min, cardiac index 2.4 L/min/m2, stroke volume 72 mL, and stroke volume
indexed to body surface area 24 mL/m2.
group compared with the non-obese group (mean,
4.8 L/min and 4.2 L/min, respectively; p < 0.01) [Figure
2]. LVEF was significantly increased in the obese group
(mean, 65.2% vs 58%; p < 0.03) [Figure 3]. Figure 4
shows a box plot of SV in the 2 groups.
Despite the significant increases in CO and LVEF
associated with obesity, t-tests revealed no difference
between the obese and non-obese groups with respect
to mean CI (p = 0.92). Figure 5 shows regression plots
of BMI versus CI in the obese and non-obese groups.
DISCUSSION
Abnormal haemodynamic parameters are primary indicators of cardiovascular disease and can be used to
assess cardiovascular pathophysiology in the clinical
setting. CO has been described as the ultimate expression of cardiovascular performance.1 In mammalian
tissue, CO at rest is 0.1 L/min/kg and is therefore
228
linearly related to body weight. By indexation to BSA,
CI allows appropriate comparison between individuals
of differing body weight and permits satisfactory
determination of normal ranges for overall cardiac pump
function within a population. Determination of the CI
for the individual patient in the outpatient setting is seldom performed but may provide insight into individual
haemodynamics and by extension, into the patient’s
symptoms and treatment.
The most popular methods for measuring CO in current clinical use are thermodilution techniques in the
ITU setting, which exploit the principle of the StewartHamilton equation and appear to be more practical than
the earlier Fick principle or dye dilution method. The
Stewart-Hamilton Equation can be expressed as:
CO = Q/∫ P(t)/dt,
where Q = injected dose and ∫P(t)/dt = integral of tracer
concentration from 0 to ∞. However, this method has
J HK Coll Radiol 2005;8:226-232
JP Coffey, JC Hill
(a)
(b)
CO (non-obese)
CI (non-obese)
CO (obese)
CI (obese)
2
3
4
5
L/min
6
7
8
1 1.2 1.4 1.6 1.8 2 2.2 2.4 2.6 2.8 3 3.2 3.4 3.6
L/min/m2
Figure 2. Box plot depicting (a) cardiac output (CO) and (b) cardiac index (CI) range and values for obese and non-obese patients.
drawbacks, in that flow rate theoretically should be
constant; anatomical abnormalities and irregular respiration can introduce inaccuracies and the injection must
be made at a constant rate over a brief interval.17-19 Readings for CO by this method can still vary in the individual patient, but it appears to be more accurate and
less operator-dependent than CO measurement using
echocardiography.20
Cardiac volumetric determination by gated SPECT
MIBI imaging has the advantage of being largely operator-independent and of being non invasive. Satisfactory correlation is reported in the literature between
volumetric measurements by this method and echocardiography and magnetic resonance imaging.3-6 To
date, its use for CO evaluation has not been reported in
the literature despite the potential advantages of the
technique.
An association between obesity and elevated CO has
long been observed and increased vascular volume,
enlarged vascular tree and elevated CO were thought
essential to supply the metabolic demands of the
expanded adipose tissue volume.21 Fat-free mass is also
increased in obesity and its higher metabolic requirements may be a greater determinant of changes in CO
and SV in obesity.13 Obesity has been implicated in the
deaths of 300,000 adults annually in the USA and over
20% of the adult American population are classified as
clinically obese. An elevated two-fold risk of coronary
artery disease has been observed in obese women22-24
and the Framingham study has revealed an increased
risk for coronary artery disease by a factor of 2.4 in
obese women and of 2 in obese men under age 50.25
Obesity is prominently associated with congestive
cardiac failure and appears to be an important risk
factor for this disorder. Risk of heart failure increases
proportionally with BMI26-29 and of all the cardiac complications of obesity, obese cardiomyopathy appears the
most serious with left ventricular dilatation, cardiomegaly and myocyte hypertrophy predisposing to ventricular arrythmias and altered myocardial contractility.
LVEF
(non-obese)
SV (non-obese)
LVEF
(obese)
SV (obese)
20
30
40
50
60
Percent
70
80
90
Figure 3. Box plot depicting range for left ventricular ejection
fraction (LVEF) for obese and non-obese patients.
J HK Coll Radiol 2005;8:226-232
20
30
40
50
60
70
80
90
mL
Figure 4. Box plot depicting range for stroke volume (SV) of obese
and non-obese patients.
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Cardiac Index and Obesity: SPECT MIBI
(b)
60
30
55
28
50
26
BMI <30
BMI >30
(a)
45
24
40
22
35
20
0
18
1.4 1.6 1.8
2
2.2 2.4 2.6 2.8
Cl (obese)
3
3.2 3.4 3.6
1 1.2 1.4 1.6 1.8 2 2.2 2.4 2.6 2.8 3 3.2 3.4
Cl (non-obese)
Figure 5. Simple regression graphs of body mass index (BMI) and cardiac index (CI) for (a) obese (r = –0.016, p < 0.01) and (b) non-obese
patients (r = –0.018, p < 0.01).
Pascual et al 8 have observed alterations in diastolic
function in slightly and moderately obese patients as
well as the severely obese. These alterations of diastolic
function were correlated strongly with BMI. Cardiac
adaptations to volume overload in obesity are manifest
as eccentric hypertrophy and anomalies of diastolic function from the initial stages of obesity, suggesting that
features of obese cardiomyopathy arise in all obese
patients.30,31
To date CI, despite being an important overall haemodynamic parameter, has not been systematically compared between a non-obese and obese group of patients
in a clinical setting. Our findings indicated a clinically
significant increase in CO for the obese group (consistent
with previous literature) but no significant alteration in
CI. This suggests that obese patients have a similar
haemodynamic status with respect to overall tissue
perfusion as their non-obese counterparts. Increased
myocardial contractility or hypersystolic function in the
form of increased ejection fraction appears to account
for this, in part, in our patient group.
CI and haemodynamic status are dependent on three
principal variables: HR (chronotropic input), SV (inotropic input) and mean arterial pressure. These variables
may alter over short intervals; therefore, assessing
haemodynamics over a 20-minute interval scanning
time necessarily represents a simplification of the true
global perfusion status. Another limitation of the study
is the known overestimation of LVEF and SV with
small left ventricular capacity at end-diastole in gated
SPECT perfusion imaging. This source of error could
lead to underestimation of true prevalence of reduced
CO and CI in this patient subgroup.32-34 Use of a standard division of the cardiac cycle into eight intervals
can lead conversely to underestimation of the LVEF in
some cases.35 A further limitation of the study is the
exclusive use of BMI in categorising obesity with no
assessment of distribution of body fat. Correlation of
abdominal fat, particularly in males, with CI might have
produced a stronger relationship. However, despite this,
the gender distribution of the two groups (51% female)
does not necessarily preclude extrapolation of results
to the general population of symptomatic patients.
Of interest is the finding of a low CI in both groups,
with a mean value of 2.19 L/min/m2 overall for a population with an overall mean age of 57 years. This appeared to be independent of the presence of perfusion
anomalies on the initial post-stress study. The finding
suggests that global impairment of haemodynamic
function in the form of reduced CI may contribute to
patients’ symptoms in the absence of obvious myocardial perfusion defects.
Many factors, such as heart size, perfusion defects and
subdiaphragmatic activity of tracer together with quantitative software, reconstruction algorithm and filter
parameters may affect EF calculation and volumetric
analysis. However, in a study population of 112 patients,
these factors may reasonably be expected to apply uniformly across the entire group. No obvious bias was
present to account specifically for differences between
groups. While bias cannot be discounted, it appears
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J HK Coll Radiol 2005;8:226-232
JP Coffey, JC Hill
unreasonable to dismiss obesity as a factor in inter-group
disparity in EF.
7.
Soft-tissue attenuation can affect the accuracy of scintigraphic quantitative measurements, particularly in obese
subjects with production of artefactual perfusion defects.
This could, on occasion, lead to spurious perfusion
defects with possible consequent underestimation of
volumetric data.
In this study, only the post-stress gated data were used
in calculating CO and CI and some degree of myocardial stunning might account for the low readings for CI
in some cases. This concern would appear to be small,
however, in view of the fact that overall LVEF readings were high with only 12 patients (10%) having abnormally low LVEF. In addition, comparison of the
post-stress and resting volumetric data acquired for 32
patients with suspected perfusion anomalies showed
no statistically significant differences between the two
sets of volumetric data.
8.
9.
10.
11.
12.
13.
14.
In conclusion, this study supports the use of volumetric
data from myocardial SPECT MIBI perfusion imaging
in calculating CO and CI in an outpatient clinical setting.
The prevalence of abnormally reduced CI was found to
be unexpectedly high in both obese and non-obese
patients, suggesting that this should be taken into account in assessment and treatment of symptoms. Obese
patients had a similar haemodynamic status to non-obese
patients, despite overall elevated CO and ejection
fraction.
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