Variables that influence the indication of a second myocardial

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Rev Esp Med Nucl Imagen Mol. 2014;33(2):72–78
Original Article
Variables that influence the indication of a second myocardial perfusion
gated-SPECT after a normal stress-rest gated SPECT夽
G. Romero-Farina a,∗ , J. Candell-Riera a , S. Aguadé-Bruix b , G. Cuberas-Borrós a ,
M.N. Pizzi a , A. Santos a , G. de León a , D. García-Dorado a
a
b
Servicio de Cardiología, Hospital Universitari Vall d’Hebron, Institut de Recerca (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain
Servicio de Medicina Nuclear, Hospital Universitari Vall d’Hebron, Institut de Recerca (VHIR). Universitat Autònoma de Barcelona, Barcelona, Spain
a r t i c l e
i n f o
Article history:
Received 10 April 2013
Accepted 30 June 2013
Keywords:
Gated-single-photon emission computed
tomography
Stress test
Myocardial ischemia
Coronary artery disease
a b s t r a c t
Objective: The objective of this study was to investigate predictor variables at the moment of normal
stress-rest myocardial perfusion gated SPECT for the indication of a second gated SPECT.
Materials and methods: A prospective, single center cohort study was conducted. We evaluated 2326
consecutive patients (age 63.6 ± 13 years, 57.3% females) without perfusion defects and with normal left
ventricular ejection fraction on a myocardial perfusion gated SPECT. Clinical and stress test variables
were studied to predict indication of a second gated SPECT and presence of reversible perfusion defects
in the second gated SPECT.
Results: During a mean follow-up of 3.6 ± 2 years a second gated SPECT was performed in 286 patients
(12.3%). Independent predictor variables of a second gated SPECT were presence of three or more cardiovascular risk factors (2 : 5.510; HR: 1.4; p = 0.019), previous acute myocardial infarction (2 : 3.867; HR:
1.4; p = 0.049), previous coronary revascularization (2 : 41.081; HR: 2.5; p < 0.001), and a positive stress
test (2 : 8.713; HR: 1.5; p = 0.003). Observation of perfusion defects in the 280 patients in whom a second
stress-rest gated SPECT was performed was more likely in male patients (2 : 4.322; HR: 1.9; p = 0.038)
who had a first pure pharmacological gated-SPECT (2 : 7.182; HR: 2.6; p = 0.007).
Conclusions: In patients with a first normal myocardial perfusion gated SPECT, various clinical factors
and variables derived from the stress test affect the indication of a second gated SPECT and the presence
of ischemia in the latter.
© 2013 Elsevier España, S.L. and SEMNIM. All rights reserved.
Variables que influyen en la indicación de una segunda gated-SPECT de
perfusión miocárdica después una gated-SPECTde estrés-reposo normal
r e s u m e n
Palabras clave:
Gated-tomografía computarizada por
emisión de fotones individuales
Prueba de estrés
Cardiopatía isquémica
Enfermedad coronaria
Objetivo: El objetivo de este estudio fue investigar qué variables en el momento de la práctica de una
gated-SPECT de perfusión miocárdica normal son predictoras de la indicación de una segunda gatedSPECT.
Material y métodos: Estudio unicéntrico, prospectivo de cohorte. Se incluyeron consecutivamente 2.326
pacientes (edad 63,6 ± 13 años, 57,3% mujeres) sin defectos de perfusión y con una fracción de eyección
del ventrículo izquierdo normal en una gated-SPECT de perfusión miocárdica estrés-reposo. Se estudiaron
variables clínicas y ergométricas predictoras de la indicación de una nueva gated-SPECT y de la presencia
de defectos reversibles de perfusión en esta última.
Resultados: Durante un seguimiento medio de 3,6 ± 2 años después de una gated-SPECT normal se practicó una segunda gated-SPECT en 286 pacientes (12,3%). Las variables predictoras independientes que
influyeron en la indicación de una segunda gated-SPECT fueron la presencia de 3o más factores de riesgo
cardiovascular (2 : 5501; HR: 1,4; p = 0,019), el antecedente de infarto agudo de miocardio (2 : 3862;
HR: 1,4; p = 0,049), la revascularización coronaria previa (2 : 41,063; HR: 2,5; p < 0,001), y una prueba de
estrés positiva (2 : 8699; HR: 1,5; p = 0,003). La observación de defectos de perfusión en los 280 pacientes
en que se realizó una segunda gated-SPECT de estrés-reposo fue más probable en pacientes de sexo masculino (2 : 4,322; HR: 1,9; p = 0,038) que realizaron una primera gated-SPECT farmacológica pura (2 :
7,182; HR: 2,6; p = 0,007).
Abbreviations: SPECT, single-photon emission computed tomography; CVRF, cardiovascular risk factors; HR, hazard ratio; CI, confidence interval.
Abreviaturas: SPECT, tomografía computarizada por emisión de fotón único; FRCV, factores de riesgo cardiovascular; HR, hazard ratio; IC, intervalo de confianza.
夽 Please cite this article as: Romero-Farina G, Candell-Riera J, Aguadé-Bruix S, Cuberas-Borrós G, Pizzi M, Santos A, et al. Variables que influyen en la indicación de una
segunda gated-SPECT de perfusión miocárdica después una gated-SPECTde estrés-reposo normal. Rev Esp Med Nucl Imagen Mol. 2014;33:72–78.
∗ Corresponding author.
E-mail address: [email protected] (G. Romero-Farina).
2253-8089/$ – see front matter © 2013 Elsevier España, S.L. and SEMNIM. All rights reserved.
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G. Romero-Farina et al. / Rev Esp Med Nucl Imagen Mol. 2014;33(2):72–78
73
Conclusiones: En los pacientes con una gated-SPECT de perfusión miocárdica normal diversos factores
clínicos y variables derivadas de la prueba de estrés influyen en la indicación de una segunda gated-SPECT
y en la presencia de isquemia en esta última.
© 2013 Elsevier España, S.L. y SEMNIM. Todos los derechos reservados.
Introduction
The role of myocardial perfusion stress SPECT (single photon emission computed tomography) in the prognostic staging
of patients with or suspected of having coronary disease is well
established.1,2 When the result of this study is normal the possibility of presenting severe complications (death of cardiovascular origin or acute myocardial infarction) during the first years is generally
lower than 1%,2–9 although different clinical, ergometric variables
derived from the stress test are known to modify this percentage.
On the other hand, it is relatively frequent for some patients with
a normal SPECT to undergo another SPECT during the clinical outcome of the disease, showing perfusion defects in the second study.
Taking into account that no previous study has analyzed the variables which may influence the indication for a second gated-SPECT
following a previous normal study, the aim of the present study was
to analyze the predictive factors for the indication of a second study
when the results of the first are normal and determine which factors may be predictive of the positivity of the second gated-SPECT
study.
Methods
Design
In a prospective, single center cohort study we included a total
of 2326 consecutive patients (age 63.6 ± 13 years, 57.3% females)
referred to our Nuclear Cardiology Unit with known or suspected
of coronary artery disease or suspicion of the same from 1998 to
2008 with a normal stress-rest myocardial perfusion gated-SPECT.
We excluded patients with valvular disease, non-ischemia myocardiopathy as well as those in whom fixed or reversible perfusion
defects were observed. We analyzed clinical, ergometric variables,
ventricular volumes and the left ventricular ejection fraction by
gated-SPECT in all the patients and reviewed the 286 patients
(12.3%) undergoing a second myocardial perfusion gated-SPECT
according to the criteria of the cardiologist. The study was approved
by the Ethical Committee of our hospital. The procedures used in
the patients were performed after obtaining informed consent.
a semicircular orbit of 180◦ in a step and shoot mode initiated in
the right anterior oblique at 45◦ , with detection every 3◦ (25 s).
The detection was synchronized with the R wave of the electrocardiogram and the cardiac cycles were divided into 8 fractions. The
reconstruction system used was filtered backprojection (Order 5
Butterworth filter, slice frequency 0.4). Correction of attenuation
and dispersion was not applied. Left ventricular ejection fraction
and the ventricular volumes were automatically calculated in the
rest gated-SPECT using the QGS program (Cedars-Sinai Medical
Center, Los Angeles, CA, USA). The interpretation of the images was
always made by the consensus of 2 experienced observers (one
cardiologist and one nuclear physician). A study was defined as
normal when no fixed or reversible perfusion defect was present,
and the left ventricular ejection fraction was greater than 50%.
Statistical analysis
The continuous variables were expressed as mean and standard
deviation (±) and the categorical variables as percentages. The
continuous variables were compared using the Student’s t test
for unpaired samples. Differences between percentages were
compared with the Chi-square test, and when the number of
values expected was lower than 5 the Fisher exact test was used.
The differences with respect to the presence of angina, myocardial
infarction and coronary revascularization between the first and
second SPECT were analyzed with the McNemar test. Different
Cox multiple regression models were used for the analysis of the
variables predictive of a second gated-SPECT and of myocardial
ischemia in the second study. The hazard ratios (HR) with their
respective confidence intervals (CI) were evaluated using the
stepwise forward (LR) method with a probability of entry and
removal of 0.05 and 0.10, respectively. For choosing the final
model and calculation of the predictive value the sensitivity,
specificity, correct classifications and C statistics of each model
were evaluated. The proportionality assumption and the log-linear
relationship of each model were compared. The accumulated
incidence of a second gated-SPECT was shown in Kaplan–Meier
curves. Differences were considered significant with a p < 0.05.
All the data were analyzed using the SPSS program for Windows,
version 15.0 (SPSS Inc, Chicago, IL, USA) and MedCal® .
Stress-rest myocardial perfusion gated-SPECT
Results
A single day protocol was used for the first and second gatedSPECTs (first the stress and then rest) with technetium compounds
(99m Tc-methoxy-isobutyl-isonitryl or 99m Tc-tetrofosmin). In the
first gated-SPECT 68.7% of the patients underwent a stress test
limited by symptoms, 16.8% did a submaximum + dipyridamole
stress test and 13.5% only underwent a pharmacologic test
(dipyridamole: 217 patients; dobutamine: 92 patients). In the
286 patients in whom a second SPECT was indicated, 6 were of
rest and 280 stress-rest. In these patients 46.6% performed an
stress test limited by symptoms, 11.9% a submaximum stress
test + dipyridamole, and 11.4% only a pharmacologic test (dipyridamole: 14 patients; dobutamine: 18 patients).10 The first dose
of the technetium compound was administered 30–60 s prior to
the end of the stress test and was of 8 mCi, and the second dose
(rest) was of 24 mCi, with an interval greater than 45 min between
each. The equipment used was a Siemens dual head E.CAM gamma
camera in a 90◦ configuration with high resolution collimator with
Table 1 shows the clinical characteristics of the patients at the
time of the first gated-SPECT in the 2326 patients (age 63.6 ± 13
years, 57.3% females) included in the study. During the mean
inter SPECT follow-up of 3.6 ± 2 years a second gated-SPECT was
performed in 280 (12%) of the patients (mean age 63.3 ± 10 years,
49% females). In the patients undergoing the second gated-SPECT
the prevalence of previous myocardial infarction (16.15 vs. 9.4%;
p < 0.001) and coronary revascularization (25.9 vs. 10%; p < 0.001)
was significantly greater than in those in whom a second gatedSPECT was not indicated. The mean time to perform a second
gated-SPECT in the patients with known coronary artery disease
was slightly, albeit not significantly, lower than in the patients
without previous coronary artery disease (1.9 vs. 2.2 years;
p = 0.114). All the patients in whom a second gated-SPECT was performed were symptomatic with chest pain; 7.5% of these patients
presented acute myocardial infarction and 14.6% underwent
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G. Romero-Farina et al. / Rev Esp Med Nucl Imagen Mol. 2014;33(2):72–78
Table 1
Characteristics of the patients at the time of the first normal gated-SPECT.
Global 2326
1 SPECT n = 2040
2 SPECTs n = 286
p
Age (years)
BMI
Males (%)
Diabetes mellitus (%)
Arterial hypertension (%)
Hypercholesterolemia (%)
Smoking (%)
1 CVRF (%)
2 CVRF (%)
CVRF ≥3
63.5 ± 13
28.2 ± 16
993 (42.7)
419 (18)
1371 (58.9)
1121 (48.2)
753 (32.4)
709 (30.5)
821 (35.3)
423 (18.2)
63.6 ± 13
28.1 ± 14
847 (41.5)
354 (17.4)
1195 (58.6)
960 (47.1)
649 (31.8)
630 (30.9)
725 (35.5)
347 (17)
63.3 ± 10
29.8 ± 15
146 (51)
65 (22.7)
176 (61.5)
161 (56.3)
104 (36.4)
79 (27.6)
96 (33.6)
76 (26.6)
0.731
0.243
0.002
0.027
0.341
0.003
0.124
0.262
0.513
<0.001
Clinical history
Previous AMI (%)
Previous CR (%)
Angina (%)
Chest pain (%)
237 (10.2)
279 (12)
246 (10.6)
2080 (89.4)
191 (9.4)
205 (10)
207 (10.1)
1833 (89.9)
46 (16.15)
74 (25.9)
39 (13.6)
247 (86.4)
<0.001
<0.001
0.072
0.072
ECG
LBBB (%)
PM (%)
78 (3.4)
21 (0.9)
63 (3.1)
19 (0.9)
15 (5.2)
2 (0.7)
Type of stress
ST (%)
ST + PHARM (%)
PHARM (%)
Positive ST (%)
1640 (70.5)
377 (16.2)
309 (13.3)
422 (18.1)
1421 (69.7)
343 (16.8)
276 (13.5)
347 (17)
219 (76.6)
34 (11.9)
33 (11.5)
75 (26.2)
Gated-SPECT
LVEF (%)
TDV (ml)
TSV (ml)
65 ± 151
76.7 ± 40.3
31.3 ± 22.2
64.9 ± 15.4
76.9 (25)
31.6 (20)
66.3 ± 13
74.8 (27)
28.6 (15)
0.058
0.698
0.016
0.034
0.353
< 0.001
0.103
0.399
0.115
1 SPECT: patients only undergoing the first normal SPECT. 2 SPECTs: patients undergoing the second SPECT, LBBB: left bundle branch block, PHARM: pharmacologic test, LVEF:
left ventricular ejection fraction, CVRF: cardiovascular risk factors; AMI: acute myocardial infarction, BMI: body mass index, PM: pacemaker, ST: stress test, CR: coronary
revascularization, TDV: telediastolic volume, TSV: telesystolic volume.
coronary revascularization
gated-SPECT study.
between
the
first
and
second
Predictors of a second gated-SPECT
In the univariate analysis the percentages of males, patients
with diabetes mellitus, hypercholesterolemia, ≥3 cardiovascular
risk factors (CVRF), a history of previous myocardial infarction,
previous coronary revascularization who did exercise and those
with a positive clinical stress and/or electrocardiogram for myocardial ischemia were significantly higher in the patients in whom a
second gated-SPECT was indicated (Table 1). In the Cox multivariate analysis (constituted by the 12 variables in Table 2) the
predictive variables (C statistics: 0.61 [CI 95%: 0.58–0.62] p < 0.001;
sensitivity: 72% [CI 95%: 66–76.8]; specificity: 50% [CI 95%:
45.9–50.3] for a second gated-SPECT (−2 Log likelihood, 4094.6;
2 : 85,494; p < 0.001) were (Table 2) ≥3 CVRF (HR: 1.4; p = 0.019),
a history of myocardial infarction (HR: 1.4; p = 0.049), previous
coronary revascularization (HR: 2.5; p < 0.001) and a positive stress
test (HR: 1.5; p = 0.003). Fig. 1 shows the Kaplan–Meier curves
of these predictors during the follow-up after the first normal
gated-SPECT. With respect to the reference category (without
predictors of a second SPECT), the HR for one predictor was 2.1
(CI 95%: 1.6–2.8; 2 : 25,926; p < 0.001), being 2.6 (CI 95%: 1.9–3.6;
: 31,166; p < 0.001) for 2 predictors and 3.4 (CI 95%: 2.2–5.3;
2 : 30,391; p < 0.001) (−2 Log likelihood, 4,097,472; 2 : 68,521;
p > 0.001) for ≥3 predictors. The probability of indicating a second
SPECT during the follow-up rose with the number of predictor
variables found (log rank test for trend, 2 : 616,410; p < 0.001).
Predictors of myocardial ischemia in the second gated-SPECT
Reversible perfusion defects were detected in 58 of the 280
(20.7%) patients undergoing a second stress-rest SPECT: mild
(sum of differential score between 2 and 3) in 43 patients (74.1%)
and moderate (sum of differential score between 4 and 6) in
15 patients (25.9%). In 26 patients the defects were of anterior,
septal and/or apical localization, being inferolateral in 32 patients.
Table 3 shows the characteristics of the first SPECT in the patients
with and without reversible defects in the second SPECT. The only
significant variable was having performed a purely pharmacologically stimulated ischemia test in the first SPECT (207 vs. 9%;
p = 0.013). Table 4 describes the HR of the significant variables in
the univariate analysis and those included by clinical consensus
for multivariate analysis. The independent predictor variables of
myocardial ischemia in the second SPECT were: male (HR: 1.9; CI
95%: 1.1–3.7; p = 0.038) and the performance of a purely pharmacological test (HR: 2.6; CI 95%: 1.3–5.3; p = 0.007) during the first
SPECT (Fig. 2A and B). Fig. 3 provides an example of a normal first
SPECT and a second SPECT with a reversible perfusion defect.
With respect to the category of reference (without predictors of
myocardial ischemia in the second SPECT), the HR for one predictor was 1.4 (CI 95%: 0.7–2.5; 2 : 0.963; p = 0.326) and 2.3 (CI 95%:
1.1–5.4; : 3948; p = 0.047) (−2 Log likelihood, 536,509; 2 : 14,501
p = 0.025) for 2 predictors. The probability of myocardial ischemia
in the second SPECT rose significantly on summing these predictors
(log rank test for trend, 2 : 39,624; p = 0.0465).
Discussion
In the database of our Nuclear Cardiology Unit the prevalence
of a normal stress-rest myocardial perfusion gated-SPECT was of
34% (2326/6811), and in 12% of these patients (286/2326) a second gated SPECT was indicated for health care reasons. Our results
demonstrate that several clinical factors and those achieved from
the stress test performed influence the indication for a new myocardial perfusion gated-SPECT study despite the first being normal.
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75
Table 2
Variables at the time of the first gated-SPECT which were predictive of the need for a second gated-SPECT.
Variables
Univariate
Age
Males
Diabetes
Hypercholesterolemia
≥3 CVRF
Previous angina
LBBB
LVEF
Previous AMI
Previous CR
ET
Positive ST
2
HR (CI 95%)
1.591
8.644
1.121
12.044
12.652
1.914
1.276
5.429
12.316
60.856
3.334
11.529
1.1 (0.9–1.1)
1.4 (1.1–1.8)
1.2 (0.9–1.5)
1.5 (1.2–1.9)
1.6 (1.2–2.1)
1.3 (0.9–1.8)
1.4 (0.8–2.3)
0.9 (0.9–0.99)
1.8 (1.3–2.4)
2.9 (2.2–3.7)
1.3 (0.9–1.7)
1.6 (1.2–2.1)
Multivariate
p
0.442
0.003
0.29
0.001
<0.001
0.167
0.259
0.02
<0.001
<0.001
0.068
0.001
2
HR (CI 95%)
5.501
1.4 (1.05–1.8)
0.019
3.862
41.063
1.4 (1.1–1.8)
2.5 (1.9–3.3)
0.049
<0.001
8.699
1.5 (1.1–1.9)
0.003
p
LBBB: left bundle branch block, HR: hazard ratio, CI: confidence interval, LVEF: left ventricular ejection fraction, CVRF: cardiovascular risk factors, AMI: acute myocardial
infarction, ET: effort test, ST: stress test; CR: coronary revascularization.
Although the literature has important information related to the
favorable prognosis in patients with a normal myocardial perfusion
SPECT,2–9 the variables influencing the indication for a second
SPECT during follow-up and the presence of patterns of reversibility
(ischemia) in the second remain unknown.
and coronary revascularization prior to the first gated-SPECT and
a positive stress test at the time of the first study.
It is known that patients with the greatest number of CVRF have
a worse prognosis11 and that in clinical practice the proportion of
diagnostic tests indicated in these patients is greater. On the other
hand, it has been observed that in patients without known coronary
artery disease and with a normal stress SPECT study, the long-term
follow-up is significantly affected by the burden of the CVRF.12 In
a population of 2597 patients with no history of coronary disease
and with a normal stress SPECT followed over a mean of 6.8 years,
Supariwala et al.13 observed that the total annual mortality was of
Predictive variables for a second gated-SPECT
In the present study we observed that the principal variables
influencing the indication for a second gated-SPECT were the presence of 3 or more CVRF, a history of acute myocardial infarction
100
A
Probability in a 2nd SPECT (%)
Probability in a 2nd SPECT (%)
100
80
60
40
≥ 3 CVRF
< 3 CVRF
Chi-square: 12.8889
p<0.001
20
0
B
80
60
40
With previous AMI
Without previous AMI
Chi-square: 12.6453
p<0.001
20
0
0
2
1
3
4
5
6
0
1
Number of patients at risk
<3 CVRF
1902
1551
≥3 CVRF
423
363
1248
996
768
574
402
295
245
168
115
65
Number of patients at risk
Without previous AMI
2088
1710
With previous AMI
237
204
100
C
80
60
40
With previous CR
Without previous CR
Chi-square: 66.7071
p<0.001
20
4
5
6
Follow-up (years)
Probability in a 2nd SPECT (%)
Probability in a 2nd SPECT (%)
100
3
2
Follow-up (years)
1384
1119
857
629
432
159
122
79
60
35
3
4
5
6
D
80
60
40
st
Positive ST in the 1 SPECT
st
Negative ST in the 1 SPECT
Chi-square: 11.7347
p<0.0 01
20
0
0
0
1
2
4
5
6
Follow-up (years)
Number of patients at risk
Without previous CR
2046
With previous CR
279
3
0
1
2
Follow-up (years)
Number of patients at risk
st
1685
1377
1105
847
628
427
Negative ST in the 1 SPECT
1903
1570
1254
1009
755
566
391
289
232
181
123
76
st
229
166
136
89
61
40
Positive ST in the 1 SPECT
422
344
Fig. 1. Kaplan–Meier analysis of the accumulated incidence of a second SPECT in relation to its predictive variables. (A) Cardiovascular risk factors (CVRF). (B) Acute myocardial
infarction (AMI) prior to the first SPECT. (C) Coronary revascularization (CR) prior to the first SPECT. (D) Positive stress test (ST) in the first SPECT.
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G. Romero-Farina et al. / Rev Esp Med Nucl Imagen Mol. 2014;33(2):72–78
Table 3
Characteristics of the patients at the time of the first gated-SPECT in relation to the presence of ischemia in the second gated-SPECT.
Global
2 SPECT
No ischemia n = 222
Ischemia n = 58
p
Age (years)
BMI
Males (%)
Diabetes mellitus (%)
Arterial hypertension (%)
Hypercholesterolemia (%)
Smoking (%)
1 CVRF (%)
2 CVRF (%)
≥3 CVRF
63.5 ± 10.7
29.9 ± 16
143 (51.1)
64 (22.9)
174 (62.1)
158 (56.4)
101 (36.1)
77 (27.5)
94 (33.6)
75 (26.8)
63.1 ± 10.8
30.6 ± 19
110 (49.5)
53 (23.9)
143 (64.4)
126 (56.8)
76 (34.2)
126 (56.8)
71 (32)
62 (27.9)
65.1 ± 10.5
27.7 ± 5
33 (56.9)
11 (19)
31 (53.4)
32 (55.2)
25 (43.1)
32 (55.2)
23 (39.7)
13 (22.4)
0.731
0.559
0.396
0.428
0.125
0.828
0.210
0.828
0.271
0.398
Clinical history
Previous AMI (%)
Previous CR (%)
Angina (%)
Chest pain (%)
45 (16.1)
73 (26.1)
38 (13.6)
242 (86.4)
37 (16.7)
56 (25.2)
34 (15.3%)
188 (84.7%)
8 (13.8)
17 (29.3)
4 (6.9%)
54 (93.1)
0.596
0.528
0.096
0.096
ECG
LBBB (%)
PM (%)
15 (5.4)
2 (0.7)
13 (5.9)
2 (0.9)
2 (3.4)
0
0.468
1
Type of stress
ST (%)
ST + PHARM (%)
PHARM (%)
Positive ST (%)
214 (76.4)
34 (12.1)
32 (11.4)
74 (26.4)
171 (77)
31 (14)
20 (9)
57 (25.7)
43 (74.1)
3 (5.2)
12 (20.7)
17 (29.3)
0.644
0.068
0.013
0.576
Gated-SPECT
LVEF (%)
TDV (ml)
TSV (ml)
66.4 ± 13
74.9 ± 30
28.6 ± 19
66.6 ± 13
75.6 ± 10
29.5 ± 3
65.6 ± 12.1
72.2 ± 16
26.6 ± 10
0.618
0.558
0.521
LBBB: left bundle branch block, PHARM: pharmacologic test, LVEF: left ventricular ejection fraction, CVRF: cardiovascular risk factors; AMI: acute myocardial infarction, BMI:
body mass index, PM: pacemaker, ST: stress test, CR: coronary revascularization, TDV: telediastolic volume, TSV: telesystolic volume.
Table 4
Variables at the time of the first gated-SPECT which were predictive of myocardial ischemia in the second gated-SPECT.
Variables
Multivariatea
Univariate
2
First gated-SPECT
Male
Angina
Previous AMI
Previous CR
Pharmacologic test
Positive ST
2
HR (CI 95%)
p
HR (CI 95%)
p
2.813
3.320
0.020
1.039
6.501
1.077
1.6 (0.93–2.7)
0.4 (0.1–1.1)
0.9 (0.4–2)
1.3 (0.7–2.4)
2.3 (1.2–4.4)
1.4 (0.8–2.3)
0.094
0.068
0.888
0.308
0.011
0.299
4.322
1.9 (1.1–3.7)
0.038
7.182
2.6 (1.3–5.3)
0.007
HR: hazard ratio, CI: confidence interval, AMI: acute myocardial infarction, ST: stress test, CR: coronary revascularization.
a
Adjusted for age, diabetes, ≥3 cardiovascular risk factors and left ventricular ejection fraction.
100
A
Probability of ischemia in
the 2nd SPECT (%)
Probability of ischemia in
the 2nd SPECT (%)
100
80
60
40
Male
Female
Chi-square: 4.322
p=0.038
20
0
B
80
st
60
With PHARM test in the 1 SPECT
st
Without PHARM test in the 1 SPECT
Chi-square: 6.8899
p<0.038
40
20
0
0
1
2
3
4
5
6
Follow-up (years)
Number of patients at risk
Female
97
137
Male
104
143
0
1
2
3
4
5
6
68
42
18
9
8
6
0
0
Follow-up (years)
57
41
27
12
7
50
35
21
6
2
Number of patients at risk
st
Without PHARM test in the 1 SPECT
248
179
97
st
With PHARM test in the 1 SPECT
32
22
10
Fig. 2. Kaplan–Meier analysis of the accumulated incidence of the presence of myocardial ischemia in the second SPECT in relation to its predictive variables. (A) Genre; (B)
pure pharmacological (PHARM) test in the first SPECT.
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1
EC
ELH
ELV
E
R
2
EC
ELH
ELV
E
R
Fig. 3. Example of a normal first myocardial perfusion maximum stress-rest SPECT
(1) in a patient with atypical pain after the implantation of a stent in the right
coronary artery and of a second SPECT (2) performed 2 years later in which a
moderate reversible apical defect may be observed. E: stress, EC: short axis, ELH:
long horizontal axis, ELV: long vertical axis, R: rest.
1.8% in the patients with 3 risk factors (hypertension, diabetes and
smoking), being of only 0.2% in patients with no risk factor.
The presence of known coronary artery disease was at a higher
prognostic value compared to a normal SPECT result since this indicates a population of patients with an elevated risk of new cardiac
complications.14 From a clinical point of view it is logical for a
history of acute myocardial infarction and/or coronary revascularization to carry a strict patient follow-up and thus, a greater
probability of indication for tests to rule out residual ischemia, particularly in symptomatic patients. Carryer et al., 7 observed that
a second routine SPECT following a first normal SPECT was indicated in 13% of 2354 patients with no history of coronary disease
while this percentage was of 26% in the 656 patients with already
diagnosed coronary disease. In our series of patients in whom a
second gated-SPECT was performed the prevalence of a previous
acute myocardial infarction (16.15 vs. 9.4%; p < 0.001) and previous coronary revascularization (25.9 vs. 10%; p < 0.001) was also
significantly greater than in those in whom a second SPECT was
not indicated, although no significant differences were found in
the intervals of time between the first and the second study in the
patients with and without known coronary artery disease (1.9 vs.
2.2 years; p = 0.114).
Schinkel et al.14 published a series of 147 consecutive patients
with a history of infarction and/or revascularization with a normal stress SPECT or with dobutamine followed over a mean of 6.5
years. They observed that the annual cardiac mortality was 0.5%
during the first 3 years and 1.3% during the following 3 years. The
independent predictive factors of this mortality were male genre
and the cardiac frequency by both resting and effort blood pressure. These authors concluded that in patients with this history
and with a normal SPECT it is not necessary to repeat the study
77
prior to 3 years except on the development of symptoms during the
follow-up.
In our population and excluding the patients with left bundle
branch block we also observed that the indication for a second
gated-SPECT was more often requested (26.2 vs. 17%; p < 0.001) in
patients in whom the stress test had been positive for ischemia
showing ST segment depression and/or angina in the first normal
gated-SPECT. In previous studies it has been observed that a significant ST segment depression, especially in males, even in the
presence of a normal SPECT may be highly indicative of multivessel
disease and/or of the common trunk.15 In this clinical context, and
despite a negative first study, it is logical to think that the clinician
may request a second SPECT.
Predictive variables of myocardial ischemia in the second
gated-SPECT
In the multivariate analysis of our series the principal predictive
variables for an ischemic pattern in the second SPECT were male
genre and the performance of a purely pharmacological test during the first gated-SPECT. These findings are not surprising taking
into account that, on one hand, the prevalence of coronary artery
disease is greater in men than in women of a similar age and the
fact that not being able to do physical exercise and having to do
a pharmacological test to stimulate ischemia both carry a worse
prognosis.16 The mortality is inversely related to the duration of
the exercise and is only of 0.1%/year in patients able to achieve 10
MET in the stress test.17 It is therefore logical that the cardiologists have a greater tendency to request a new study after a purely
pharmacological first SPECT, despite being normal, than in cases
in which the normal SPECT was obtained after a sufficient stress
test, particularly if this was clinically and electrocardiographically
negative.
In previous series18–21 the long-term mortality was reportedly
longer after a normal SPECT with a purely pharmacological test
compared with a SPECT performed with a stress test. In a metaanalysis of 14,918 patients from 24 studies, Navare et al.22 observed
that the percentage of complications after a SPECT was significantly
higher if a pharmacological test had been performed compared to
a stress test regardless of whether the result had been normal (1.78
vs. 0.65%; p < 0.001) or not (9.98 vs. 4.3%; p < 0.001).
Despite patients evaluated with pharmacological tests generally
presenting an older age, diabetes, arterial hypertension, and atrial
fibrillation, in a series of 6069 patients followed over a mean of 10
years Rozanski et al.23 observed that the annual mortality of the
patients who had received adenosine as the stimulation test was
2-fold greater than that of those who had performed a stress test
(3.9 vs. 1.6%; p < 0.001). In these cases the mortality was inversely
related to the duration of the exercise, being comparable to that of
adenosine in those who did not surpass 3 min in the stress test.
Limitations
This was a single center study and may have a possible bias
in that cohort studies do not allow a clear cause–effect relationship to be established. It is true that after a normal gated-SPECT
new symptoms may appear which, according to the criteria of the
attending physician, carry an indication for a second study. Indeed,
this was the main reason for indicating a second gated-SPECT. However, the objective of this study was to analyze the characteristics
of the patients in the first study which influence the indication for
a second study despite the first being normal, independently of the
symptomatology prior to the second gated-SPECT which, in general,
was chest pain in our series.
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78
G. Romero-Farina et al. / Rev Esp Med Nucl Imagen Mol. 2014;33(2):72–78
Conclusions
In patients with a normal myocardial perfusion SPECT different
clinical factors (≥3 CVRF, previous acute myocardial infarction and
coronary revascularization) and factors derived from the stress test
(angina and/or ST segment depression) influence the indication for
a second gated-SPECT during follow-up. The observation of perfusion defects in the second SPECT is more probable in males and
in patients doing a purely pharmacological first gated-SPECT.
Conflict of interests
10.
11.
12.
13.
14.
The authors declare no conflict of interests.
References
1. Shaw LJ, Iskandrian AE. Prognostic value of gated myocardial perfusion SPECT. J
Nucl Cardiol. 2004;11:171–85.
2. Shaw LJ, Hage FG, Berman DS, Hachamovitch R, Iskandrian A. Prognosis in the
era of comparative effectiveness research: where is nuclear cardiology now and
where should it be. J Nucl Cardiol. 2012;19:1026–43.
3. Elhendy A, Schinkel A, Bax JJ, van Domburg RT, Poldermans D. Long-term prognosis after a normal exercise stress Tc-99m sestamibi SPECT study. J Nucl Cardiol.
2003;10:261–6.
4. Shaw LJ, Hendel R, Borges-Neto S, Lauer MS, Alazraki N, Burnette J, et al.
Myoview Multicenter Registry. Prognostic value of normal exercise and adenosine (99m)Tc-tetrofosmin SPECT imaging: results from the multicenter registry
of 4.728 patients. J Nucl Med. 2003;44:648.
5. Metz LD, Beattie M, Hom R, Redberg RF, Grady D, Fleischmann KE. The prognostic
value of normal exercise myocardial perfusion imaging and exercise echocardiography: a meta-analysis. J Am Coll Cardiol. 2007;49:227–37.
6. Miller TD, Hodge DO, Milavetz JJ, Gibbons RJ. A normal stress SPECT scan is an
effective gatekeeper for coronary angiography. J Nucl Cardiol. 2007;14:187–93.
7. Carryer DJ, Askew JW, Hodge DO, Miller TD, Gibbons RJ. The timing and impact of
follow-up studies after normal stress single-photon emission computed tomography sestamibi studies. Circ Cardiovasc Imaging. 2010;3:520–6.
8. Hachamovitch R, Hayes S, Friedman JD, Cohen I, Shaw LJ, Germano G, et al.
Determinants of risk and its temporal variation in patients with normal stress
myocardial perfusion scans: what is the warranty period of a normal scan. J Am
Coll Cardiol. 2003;41:1329–40.
9. Schinkel AF, Boiten HJ, van der Sijde JN, Ruitinga PR, Sijbrands EJ, Valkema R,
et al. 15-Year outcome after normal exercise (99m)Tc-sestamibi myocardial
15.
16.
17.
18.
19.
20.
21.
22.
23.
perfusion imaging: what is the duration of low risk after a normal scan. J Nucl
Cardiol. 2012;5:901–6.
Zoghbi GJ, Iskandrian AE. Pharmacological stress testing. In: Iskandrian AE, García EV, editors. Nuclear cardiac imaging. Principles and applications. Oxford:
Oxford University Press; 2008. p. 293–315.
Marrugat J, Solanas P, D’Agostino R, Sullivan L, Ordovas J, Cordón F, et al. Estimación del riesgo coronario en España mediante la ecuación de Framingham
calibrada. Rev Esp Cardiol. 2003;56:253–61.
Lloyd-Jones DM, Leip EP, Larson MG, D’Agostino RB, Beiser A, Wilson PW, et al.
Prediction of lifetime risk for cardiovascular disease by risk factor burden at 50
years of age. Circulation. 2006;113:791–8.
Supariwala A, Uretsky S, Singh P, Memon S, Khokhar SS, Wever-Pinzon O, et al.
Synergistic effect of coronary artery disease risk factors on long-term survival
in patients with normal exercise SPECT studies. J Nucl Cardiol. 2011;18:207–14.
Schinkel AF, Elhendy A, Bax JJ, van Domburg RT, Huurman A, Valkema R,
et al. Prognostic implications of a normal stress technetium-99m-tetrofosmin
myocardial perfusion study in patients with a healed myocardial infarct and/or
previous coronary revascularization. Am J Cardiol. 2006;97:1–6.
Candell-Riera J, Fernández C, Escudero F, de León G, Aguadé-Bruix S, CastellConesa J. Prevalencia y significado angiográfico de la SPECT de perfusión
miocárdica normal con electrocardiograma de esfuerzo positivo. Rev Esp Cardiol.
2004;57:894–7.
Myers J, Prakash M, Froelicher V, Do D, Partington S, Atwood JE. Exercise
capacity and mortality among men referred for exercise testing. N Engl J Med.
2002;346:793–801.
Bourke JM, Charlton GT, Holland BH, Belyea CM, Watson DD, Beller GA. Prognosis
in patients achieving >= 10 METs on exercise stress testing: was SPECT imaging
useful. J Nucl Cardiol. 2011;18:230–7.
Abbott BG, Afshar M, Berger AK, Wackers FJ. Prognostic significance of ischemic
electrocardiographic changes during adenosine infusion in patients with normal
myocardial perfusion imaging. J Nucl Cardiol. 2003;10:9–16.
Klodas E, Miller TD, Christian TF, Hodge DO, Gibbons RJ. Prognostic significance
of ischemic electrocardiographic changes during vasodilator stress testing in
patients with normal SPECT images. J Nucl Cardiol. 2003;10:4–8.
Sharma J, Roncari C, Giedd KN, Fox JT, Kanei Y. Patients with adenosine-induced
ST-segment depressions and normal myocardial perfusion imaging: cardiac outcomes at 24 months. J Nucl Cardiol. 2010;17:874–80.
Johnson NP, Schimmel Jr DR, Dyer SP, Leonard SM, Holly TA. Survival by stress
modality in patients with a normal myocardial perfusion study. Am J Cardiol.
2011;107:986–9.
Navare SM, Mather JF, Shaw LJ, Fowler MS, Heller GV. Comparison of risk stratification with pharmacologic and exercise stress myocardial perfusion imaging:
a meta-analysis. J Nucl Cardiol. 2004;11:551–61.
Rozanski A, Gransar H, Hayes SW, Friedman JD, Hachamovitch R, Berman DS.
Comparison of long-term mortality risk following normal exercise vs adenosine
myocardial perfusion SPECT. J Nucl Cardiol. 2010;17:999–1008.