|ORIGINAL CONTRIBUTION - CLINICS IN NUCLEAR MEDICINE
|Year : 2016 | Volume
| Issue : 3 | Page : 131-136
Gender differences in the accuracy of stress 99mTc-sestamibi myocardial perfusion imaging
Deepa Kumar1, Ravinder S Sethi1, Sandeep Bansal2, Padma A Namgyal1, Aditi K Sehgal1, Tajamul S Malik1
1 Department of Nuclear Medicine, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, India
2 Department of Cardiology, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, India
|Date of Web Publication||27-Feb-2017|
Ravinder S Sethi
Department of Nuclear Medicine, H-Block, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi - 110 029
Source of Support: None, Conflict of Interest: None
Introduction: Coronary artery disease (CAD) is a leading cause of death in both women and men worldwide. There is under-recognition and under-diagnosis of CAD as a cause of high mortality rates in women. There is paucity of data regarding comparison of sensitivity, specificity, and accuracy of myocardial perfusion imaging-single photon emission computed tomography (MPI-SPECT) study in women and men in Indian population. Hence, this study was carried out to compare the sensitivity, specificity, and accuracy of MPI in women and men in the Indian population. Material and Methods: This retrospective study included 275 patients, 49 women and 226 men. Only patients who had coronary angiography (CAG) done within 6 months of the stress 99mTc-sestamibi MPI-SPECT study were included in the study. Two arbitrary cut-off points on CAG, i.e., ≥50% and ≥70% were used for the determination of extent of CAD. Results: Considering CAG as the gold standard with ≥50% coronary stenosis as the cut-off criteria for significant stenosis, the overall sensitivity, specificity, and accuracy, respectively, of MPI- SPECT was 80%, 65%, and 72% in women and 82%, 70%, and 76% in men (P value not significant). Considering ≥70% coronary stenosis as the cut off criteria for significant stenosis, the overall sensitivity, specificity, and accuracy, respectively, of MPI-SPECT was 88%, 57%, and 66% in women and 87%, 59%, and 70% in men (P value not significant). No significant difference was found in the sensitivity, specificity, and accuracy of left anterior descending, left circumflex artery, and right coronary artery coronary vessels among women and men for both ≥50% and ≥70% coronary stenosis as the cut off criteria. Conclusion: 99mTc-sestamibi MPI-SPECT has comparable sensitivity, specificity, and accuracy for the detection of CAD in women as it does in men.
Keywords: Coronary angiography, coronary artery disease, myocardial perfusion imaging, women
|How to cite this article:|
Kumar D, Sethi RS, Bansal S, Namgyal PA, Sehgal AK, Malik TS. Gender differences in the accuracy of stress 99mTc-sestamibi myocardial perfusion imaging. Astrocyte 2016;3:131-6
|How to cite this URL:|
Kumar D, Sethi RS, Bansal S, Namgyal PA, Sehgal AK, Malik TS. Gender differences in the accuracy of stress 99mTc-sestamibi myocardial perfusion imaging. Astrocyte [serial online] 2016 [cited 2017 Sep 20];3:131-6. Available from: http://www.astrocyte.in/text.asp?2016/3/3/131/200996
| Introduction|| |
Coronary artery disease (CAD) is a leading cause of death in both women and men worldwide. In India, studies have shown increasing prevalence of CAD, over the last 60 years, ranging from 1% to 9–10% in urban populations and <1% to 4–6% in rural populations. The Registrar General of India in their report stated that CAD led to 17% of total deaths and 26% of adult deaths in 2001–2003, which increased to 23% of total and 32% of adult deaths in 2010–2013. Eight common risk factors found responsible for acute myocardial infarctions in South Asian and Indian patients include dyslipidemia (high apolipoprotein/apolipoprotein A1 ratio), smoking or tobacco use, hypertension, diabetes, abdominal obesity, physical inactivity, low intake of fruits and vegetables, and psychosocial stress. There is under-recognition and under-diagnosis of CAD as a cause of high mortality rates in women. Timely and accurate diagnosis of CAD can significantly reduce mortality from CAD, and timely management can help in reducing the risk of mortality in both women and men. An effective diagnostic strategy is critical in women at risk as up to 40% of initial cardiac events are fatal. Noninvasive diagnostic and prognostic testing offers the potential to identify patients at increased CAD risk for instituting preventive and therapeutic interventions.99m Tc-sestamibi myocardial perfusion imaging (MPI)-single photon emission computed tomography (SPECT) study, being a noninvasive modality, plays a very important role in the detection and prognostication of CAD.
There are studies comparing the diagnostic accuracy of MPI-SPECT study in women and men in the west, showing similar accuracy found in both the sexes.,,, As the demographic profile of the Indian population differs from the Caucasian population and there is scarcity of similar studies among Indian population, this study was designed to evaluate the sensitivity, specificity, and accuracy of stress 99m Tc-sestamibi MPI-SPECT in women and compare it with men in Indian population, with coronary angiographic data used as the gold standard for the detection and quantification of CAD.
| Material and Methods|| |
This was a retrospective study. The patients who referred to the department of Nuclear Medicine for stress MPI-SPECT study between January 2010 and December 2016 were included in this study. The population for the study included 275 patients, 49 women and 226 men. Twelve percent of the women were premenopausal whereas 88% were postmenopausal. The forms of stress performed were exercise or pharmacological (dobutamine or adenosine infusion). Stress was given to the patient in the presence of a cardiologist, and stress electrocardiogram (ECG) was reported by the cardiologist only. The patients who had coronary angiography (CAG) done within 6 months of the stress 99m Tc-sestamibi MPI-SPECT study were included in the study. The angiograms were interpreted by experienced cardiologists. Patients with documented history of infarction, coronary artery bypass grafting (CABG), pathologic Q waves on the ECG, left bundle branch block (LBBB), or nonischemic cardiomyopathy were not included in the study. The patients who had any cardiac event between MPI-SEPCT and CAG were excluded from the study. Beta blockers were stopped for 3 days prior to the test.
Imaging protocol for stress myocardial perfusion
The study was conducted as a 2-day protocol stress followed by rest. Approximately 10mCi of 99m Tc-sestamibi was administered intravenously at peak stress for the stress study and on day 2 for the rest study. The SPECT acquisition was done on Philips Precedence 16 SPECT-CT gamma camera with parallel hole, low energy high-resolution collimator, with 64 projections at the rate of 30 seconds per projection using 64 × 64 matrix. A 20% window centred on 140 keV photopeak was selected. Gated SPECT was acquired at 16 frames per cycle with 180-degree arc, with continuous step and shoot method from 45 degree right anterior oblique to 45 degree left anterior oblique. Processing was done using Autospect and Autoquant softwares, using butterworth filter order 5. Short axis, horizontal long axis, and vertical long axis slices were obtained. Stress and rest images were compared.
Image analysis and diagnostic criteria
The interpretation of the MPI-SPECT was done by two experienced nuclear medicine physicians independently. Each vascular territory was either categorized as normal or abnormal having a perfusion abnormality. The perfusion defect which showed complete reversibility on rest image was considered to be ischemia. A perfusion defect on the stress image which did not show any change in the rest image was considered as a fixed defect. A perfusion defect on stress image which showed incomplete reversibility was considered as a mixed defect. Fixed defects with normal wall thickening and normal wall motion were considered to be due to soft tissue attenuation and labelled as normal (for e.g., breast and diaphragmatic attenuation). Each defect was assigned to one of the three major coronary artery territories.
CAG was performed using the Saldinger's approach. Two arbitrary cut-off points, i.e., ≥50% and ≥70% maximal lumen diameter narrowing, have been used in our study for the determination of the extent of CAD.,
The statistical tests used were the Students t-test or chi square test. Continuous data was presented as mean ± standard deviation (SD) and compared with the Students t-test. Categorical data was compared with Chi-square test. Sensitivity (%) was calculated as 100 × True positive/True positive + false negative; specificity (%) was calculated as 100 × True negative/True negative + False positive; accuracy (%) was calculated as 100 × True positive + True negative/total number of patients.
The characteristics and scan variables of patients included in the study are shown in [Table 1]. Lipid profile was available in 26 women and 145 men. Average age of the female patients was more than males and the difference was found to be significant statistically (P = 0.007). No significant difference was found in the incidence of hypertension, diabetes mellitus, hyperlipidemia, and obesity among females and males. The incidence of smoking was less in females in comparison to males (P < 0.001). Sedentary lifestyle was more commonly observed in females compared to males (P = 0.0037). No significant difference was found in the incidence of anginal chest pain among females and males. Eighty-eight percent of the women were postmenopausal, hence, our study was conducted majorly among postmenopausal female population.
Angiographic characteristics of patients
Angiographic characteristics of women and men are shown in [Table 2]. A total of 147 coronary arteries were examined in 49 women and 678 coronaries in 226 men. For ≥50% diameter stenosis criteria, the incidence of single vessel disease was 51% in women and 42% in men. Women had a higher incidence of single vessel disease and a lower incidence of double and triple vessel disease compared to men, although the difference was not significant statistically. The incidence of multivessel disease was 43% in women and 53% in men (P not significant). Multivessel disease includes both double vessel and triple vessel disease.
Stress myocardial perfusion imaging-single photon emission computed tomography study characteristics of patients
Data on the mode of stress conducted in women and men is illustrated in [Table 3]. Out of the 49 female patients included in the study, 3 underwent exercise, 18 adenosine, and 28 dobutamine stress. Out of the 226 male patients included in the study, 102 patients underwent exercise, 43 adenosine, and 81 dobutamine stress. Significantly less number of female patients underwent exercise stress.
The incidence of ischemic changes on stress ECG, ischemia on MPI-SPECT study, fixed defects, mixed lesions, and transient ischemic dilatation of the left ventricular cavity (TID) were similar among women and men with no significant difference noted statistically [Table 4].
Comparison of the extent of coronary stenosis and abnormality on MPI-SPECT study in women and men is depicted in [Table 5] and [Table 6], respectively. In women, 147 coronaries were examined, out of which 59 coronaries were normal, 18 coronaries showed <50% coronary stenosis, 27 coronaries showed 50–70% stenosis, and 43 coronaries showed >70% stenosis. In men, 678 coronaries were examined, out of which 250 coronaries were normal, 59 coronaries showed <50% coronary stenosis, 114 coronaries showed 50–70%, stenosis and 255 coronaries showed >70% stenosis.
|Table 5: Comparison of extent of coronary artery stenosis and MPI - SPECT findings in female patient (N=49, 147 coronary arteries)|
Click here to view
|Table 6: Comparison of extent of coronary artery stenosis and MPI - SPECT findings in male patients (N=226, 678 coronary arteries)|
Click here to view
Overall sensitivity and specificity of myocardial perfusion imaging-single photon emission computed tomography in women and men
Considering CAG as the gold standard with ≥50% coronary stenosis as the cut-off criteria for significant stenosis, the overall sensitivity of MPI-SPECT was 80% in women vs. 82% in men. The specificity was 65% in women compared to 70% in men. The accuracy was 72% in women and 76% in men [Table 7].
|Table 7: Overall sensitivity (%) and specificity (%) of MPI- SPECT in women and men|
Click here to view
For ≥70% coronary stenosis as the cut-off criteria for significant stenosis, the overall sensitivity of MPI-SPECT was 88% in women compared to 87% in men. The specificity was 57% in women compared to 59% in the men. The accuracy was 66% in women and 70% in men [Table 7].
Comparison of sensitivity, specificity, and accuracy of MPI-SPECT in women and men for ≥50% coronary stenosis as the cut-off criteria for significant stenosis, is illustrated in [Figure 1].
|Figure 1: Comparison of sensitivity, specificity and accuracy of SPECTMPI in women and men for ≥50% coronary artery stenosis as significant stenosis.|
Click here to view
No significant difference was found in the sensitivity, specificity, and accuracy of MPI-SPECT among women and men for both ≥50% and ≥70% stenosis as the cut-off criteria.
Individual vessel sensitivity, specificity, and accuracy
For ≥50% and ≥70% coronary stenosis as the cut-off criteria, the sensitivity, specificity, and accuracy of individual coronary vessel among women and men is illustrated in [Table 8] and [Table 9], respectively.
|Table 8: Sensitivity, specificity and predictive accuracy of MPI-SPECT for CAD in individual vessels (≥50% coronary stenosis)|
Click here to view
|Table 9: Sensitivity, specificity and predictive accuracy of MPI-SPECT for CAD in individual vessels (≥70% coronary stenosis)|
Click here to view
No significant difference was found in the sensitivity, specificity, and accuracy of left anterior descending (LAD), left circumflex artery (LCx), and right coronary artery (RCA) coronary vessels among women and men for both ≥50% and ≥70% coronary stenosis as the cut-off criteria.
| Discussion|| |
99m Tc-sestmibi MPI-SPECT is a well-documented imaging modality for the detection and prognostication of CAD. The present study demonstrated that MPI-SPECT has similar sensitivity, specificity, and accuracy in both women and men. In women, the overall sensitivity for the detection of CAD (80% for 50% coronary stenosis and 88% for 70% coronary stenosis) was similar to men (82% for 50% stenosis and 87% for 70% coronary stenosis) (P value nonsignificant). The overall specificity and accuracy was slightly lower in women compared to men, although the difference was not significant statistically. No significant difference was found in the sensitivity, specificity, and accuracy for the detection of individual diseased coronary vessel between women and men for both 50% and 70% coronary stenosis as the cut-off criteria for significant CAD.
This is one among the very few studies done to compare the sensitivity and specificity of MPI-SPECT between women and men in the Indian population.
Several investigators have shown the accuracy of MPI-SPECT imaging to be similar in men and women. Van Train et al., as part of a multicenter trial of quantitative analysis, demonstrated similar sensitivity, specificity, and normal cyrates in men and women. In 1991, Iskandrian et al. found the sensitivity of SPECT 201 T1 during pharmacologic stress to be similar in both genders. Iskandar et al. performed a systematic review of 26 studies comparing the diagnostic accuracy of MPI-SPECT in women and men and found that the diagnostic accuracy of MPI- SPECT is similar in women and men with no significant difference demonstrated statistically. Kaminek et al. performed a similar study using CAG as the gold standard and found no significant difference in the accuracy of MPI-SPECT in women and men. Amanullah et al. determined a sensitivity of 93% in women catheterized after SPECT adenosine technetium imaging. Specificity was 78% and the overall diagnostic accuracy was determined to be 88%. The same authors using the same diagnostic technique have further described a sensitivity of 91% and specificity of 70% for the diagnosis of severe or extensive coronary disease in women. Our findings are close to these previous findings.
Women included in our study had a higher average age compared to men, and the difference was found to be statistically significant. The incidence of CAD in women lags behind men by 10 years. Majority of these women (88%) were postmenopausal. Because the risk of CAD is high in the postmenopausal age group in women due to the lack of protective effect of estrogen on the heart, our findings corroborate with the documented evidence.
Women included in the study were found to have a little higher incidence of normal/minor CAD and single vessel disease and a lower incidence of triple vessel disease compared to men. Studies have found that the burden of CAD is high among women. Women are less likely than men to have obstructive CAD at the time of CAG., Despite the absence of obstructive CAD visualized on cardiac catheterization at the time of acute coronary syndrome (ACS), the prognosis of these women is not benign. Over one-half of symptomatic women without obstructive CAD continue to have symptoms and signs of ischemia and undergo repeat hospitalization and CAG.,
Significantly large proportion of women (82%) included in the present study had a sedentary lifestyle, and the resultant physical incapacity led to only 6% of women undergoing exercise stress and 94% undergoing pharmacological stress. There was a significant difference in the proportion of men and women undergoing exercise and pharmacological stress. Previous studies have demonstrated that the results of adenosine SPECT are highly concordant with exercise SPECT thallium imaging.
The sensitivity of stress MPI-SPECT for detecting LCx coronary artery disease was found to be low compared to LAD and RCA coronary artery disease in both women and men in our study. The possible reason for this finding could be the fact that assigning a perfusion defect to a specific territory is arbitrary and there may be overlap in the distribution of blood supply. Some defects of the LCx territory may have been misclassified as the defects of the LAD or the RCA territory.
Harshad et al. evaluated the prevalence of asymptomatic CAD in asymptomatic diabetics by myocardial SPECT. In comparison to CAG, the sensitivity of MPI-SPECT was 86.6% and specificity was 52%. Our study was performed among symptomatic women and men, including both diabetics and nondiabetics. The sensitivity of MPI-SPECT for detecting CAD in women and men in our study was similar to this study, however, specificity of MPI-SPECT was slightly high (65% in women and 70% in men for ≥50% coronary stenosis used as the cut-off criteria) in our study.
Loong et al. found a sensitivity of 86% and specificity of 74% of MPI-SPECT in the diagnosis of CAD. The results of our study in both women and men are consistent with this study.
According to Shawgi et al., the use of attenuation correction along with gated SPECT study would be the most useful in ruling out attenuation artifacts. The authors found that there is pronounced increase in the “normal” interpretation category when there is combined use of attenuation correction and ECG gating compared to gated MPI or MPI alone.
Although attenuation correction was not performed in our study, for fixed perfusion defects appearing as soft tissue attenuation artifacts, gated SPECT was analyzed to examine wall thickening and wall motion abnormality. Such fixed defects with normal wall thickening and normal wall motion were considered to be caused by soft tissue attenuation and labelled as normal. Still some error in the specificity and accuracy is expected in our study.
According to Iskandar et al., attenuation correction, gated SPECT, and/or prone imaging can improve the specificity of SPECT. None of the studies included in their analysis of MPI-SPECT among women reported the use of attenuation correction, and only four studies used gated-SPECT techniques. They suggested that, with the application of these techniques which have become routine procedure in many nuclear cardiology laboratories, the diagnostic accuracy of MPI-SPECT might be even better in both genders than that reported in their analysis based on available literature.
As only patients with no previous history of myocardial infarction and revascularization were included in the study, the patients in this study represent a true diagnostic population. Hence, the findings of the study may not be applicable to a broader population presenting with infarction or those who have undergone intervention.
| Conclusion|| |
The results of the study demonstrate that MPI-SPECT has comparable sensitivity and specificity for the detection of CAD in women and men. Hence, MPI-SPECT being a noninvasive diagnostic test appears to be as effective and reliable tool for detecting the extent of CAD in women, as it does in men. Our results are in accordance with previous studies.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Sharma K, Gulati M. Coronary artery disease in women: A 2013 update. Glob Heart 2013;8:105-12.
Gupta R, Mohan I, Narula J. Trends in Coronary Heart Disease Epidemiology in India. Ann Glob Health 2016;82:307-15.
Joshi PP, Islam S, Pais P, Reddy S, Dorairaj P, Kazmi K, et al
. Risk factors for early myocardial infarction in South Asians compared with individuals in other countries. JAMA 2007;297:286e94.
Mieres JH, Shaw LJ, Arai A, Budoff MJ, Flamm SD, Hundley WG, et al
. Role of Noninvasive Testing in the Clinical Evaluation of Women With Suspected Coronary Artery Disease. Circulation 2005;111:682-96.
Kang S, Berman DS, Lewin H, Miranda R, Erel J, Friedman JD, et al
. Comparative ability of myocardial perfusion single-photon emission computed tomography to detect coronary artery disease in patients with and without diabetes mellitus. Am Heart J 1999;137:949-57.
Van Train KF, Maddahi J, Berman DS. Quantitative analysis of tomographic stress thallium-201myocardial scintigrams: A multicenter trial. J Nucl Med 1990;31:1168-79.
Iskandrian AS. Heo J, Nguyen T, Beer SG, Cave V, Ogilby JD, et al
. Assessment of coronary artery disease using SPECT with thallium-201 during adenosine-induced coronary hyperemia. Am J Cardiol 1991;67:1190-4.
Iskandar A, Limone B, Parker MW, Perugini A, Kim H, Jones C, et al
. Gender differences in the diagnostic accuracy of SPECT myocardial perfusion imaging: A bivariate meta-analysis. J Nucl Cardiol 2013;20:53-63.
Kamínek M, Myslivecek M, Husák V, Koranda P, Skvarilová M, Ostransky J, et al
. The accuracy of myocardial perfusion SPECT imaging in the evaluation of coronary artery disease in women and men. Nucl Med Rev Cent East Eur 2001;4:69-72.
Berman DS, Kiat H, Friedman JD, Wang FP, Van Train KF, Matzer L. Separate aquisition rest thallium 201/stress technetium-99m sestamibi dual isotope myocardial perfusion single-photon emission computed tomography: A clinical validation study. J Am Coll Cardiol 1993;22:1455-64.
Amanullah A, Kiat H, Friedman JD, Berman DS. Adenosine technetium-99m sestamibi myocardial perfusion SPECT in women: Diagnostic efficacy in detection of coronary artery disease. J Am Coll Cardiol 1996;27:803-9.
Amanullah A, Berman DS, Hachamovitch R, Kiat H, Kang X, Friedman J. Identification of severe or extensive coronary artery disease in women by adenosine technetium-99m sestamibi SPECT. J Am Coll Cardiol 1997;80:132-7.
Fuster V, Alexander RW, O'Rourke RA, Roberts R, Spencer BK III, Weller JJ, editors. Hurst's the Heart. 10th ed. New York, NY: McGraw-Hill; 2001. pp. 3-18.
Bulliyya G. Risk of coronary heart disease in women after menopause. Indian Med Assoc 2001; 99:47880-2.
Sharaf BL1, Pepine CJ, Kerensky RA, Reis SE, Reichek N, Rogers WJ, et al
. Detailed angiographic analysis of women with suspected ischemic chest pain (pilot phase data from the NHLBI-sponsored Women's Ischemia Syndrome Evaluation [WISE] Study Angiographic Core Laboratory). Am J Cardiol 2001;87:937-41.
Kennedy JW, Kilip T, Fisher LD, Alderman EL, Gillespie MJ, Mock MB. The clinical spectrum of coronary artery disease and its surgical and medical management, 1974e1979. The Coronary Artery Surgery study. Circulation 1982;66:16-23.
Johnson BD, Shaw LJ, Pepine CJ, Reis SE, Kelsey SF, Sopko G, et al
. Persistent chest pain predicts cardiovascular events in women without obstructive coronary artery disease: Results from the NIH-NHLBI sponsored Women's Ischaemia Syndrome Evaluation (WISE) study. Eur Heart J 2006;27:1408-15.
Shaw LJ, Merz CN, Pepine CJ, Reis SE, Bittner V, Kip KE, et al
. The economic burden of angina in women with suspected ischemic heart disease: Results from the National Institutes of Health National Heart, Lung, and Blood Institute sponsored Women's Ischemia Syndrome Evaluation. Circulation 2006;114:894-904.
Gupta NC, Esterbrooks DJ, Hilleman DE, Mohiuddin SM. Comparison of adenosine and exercise thallium-201 single-photon emission computed tomography (SPECT) myocardial perfusion imaging. The GE SPECT Multicenter Adenosine Study Group. J Am Coll Cardiol 1992;19:248-57.
Harshad K, Sathyamurthy I, Ashish G, Padma D, Shelley S, Indirani M, et al
. Myocardial perfusion single photon emission computed tomography in asymptomatic diabetics. Indian Heart J 2010;62:29-34.
Loong CY, Anagnostopoulos C. Diagnosis of coronary artery disease by radionuclide myocardial perfusion imaging. Heart 2004;90(Suppl 5):v29.
Shawgi M, Tonge CM, Lawson RS, Muthu S, James J, Arumugam P. Attenuation correction of myocardial perfusion SPET in patients of normal body mass index. Hell J Nucl Med 2012;15:215-9.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8], [Table 9]