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Gender Differences in Gated Acquisition and Perfusion Tests.

During the past 10 years, nuclear medicine has been among the leaders in early detection of coronary artery disease (CAD), the leading cause of death in both men and women in the United States.[1] Recently there has been increased interest in using thallium Tl 201 and technetium Tc 99m sestamibi to assess patients with coronary artery disease. This approach has been shown to eliminate the need for fatty meals and significantly reduce the overall testing time associated with 1-day and 2-day Tc 99m sestamibi protocols.[2] This combination also provides a high sensitivity for coronary stenosis with a much shorter time in the radiology department compared to single-tracer studies using Tl 201 or Tc 99m sestamibi.

The purpose of this study was to correlate perfusion (blood flow) rest thallium/stress Tc 99m sestamibi test results with gated (wall motion) test results and to examine if there were any major differences in outcome by gender.

Review of Literature

Perfusion testing using rest/stress protocol with either Tl 201 or Tc 99m sestamibi has proven to be a valuable tool in early detection of coronary disease. Gated acquisition studies also have been successful in nuclear cardiology in assessing cardiac wall motion abnormalities.[3,4]

Thallium (Tl) is an analog of the element potassium (K), which is used by the myocardium during contraction. Thallium does not collect in the myocardium permanently, but is constantly pumped in and out of viable myocardial cells. This phenomenon makes Tl 201 an ideal agent to assess the extent of CAD and determine the viability of the affected myocardium.

Tc 99m sestamibi, marketed under the name Cardiolite (DuPont Pharmaceuticals, Wilmington, Del), readily collects in viable myocardial cells. Unlike Tl 201, Tc 99m sestamibi has little or no redistribution, which provides significant flexibility in terms of imaging.[4-7]

Electrocardiographic (ECG) gated acquisition of Tc 99m sestamibi single photon emission computed tomography (SPECT) offers the potential for simultaneous assessment of myocardial perfusion and function. Although sestamibi is injected at peak exercise in stress perfusion studies, acquisition is performed 15 minutes to 1 hour later. Thus, post-exercise gated SPECT provides rest wall motion information.[8,9]

Although the incidence of nonfatal coronary artery disease has doubled among women in the past decade and the rate of referral of women to interventional testing and revascularization also has increased, a number of studies have found that coronary artery disease in women is identified less often and at later stages than in men.[10-14] Among people 75 years of age and older, the death rate for heart disease was 16% lower for women than men. In contrast, among people 65 to 74 years of age the heart disease rate among women was half that for men.[10, 15-16]

Little has been published about gender differences in nuclear cardiology diagnostic assessment. According to Cerqueria,[17] several studies (predominantly of men) have shown that the sensitivity and specificity of radionuclide myocardial perfusion imaging during treadmill exercise or after pharmacologic vasodilatation is superior to treadmill exercise ECG testing alone. However, minimal data exist on the clinical value of exercise or pharmacologic radionuclide myocardial perfusion scintigraphy in the noninvasive diagnosis of CAD in women. Cerqueria further reported that most of the studies involved a relatively small number of patients using planar qualitative Tl 201 imaging. A 1994 study by Udelson et al[8] using Tl 201 SPECT and Tc 99m sestamibi SPECT imaging found similar sensitivities for detection of CAD in both men and women.

Methods and Procedures

The study group consisted of 47.5 patients (291 men, 184 women) referred to the nuclear cardiology laboratory for assessment of myocardial viability and regional wall motion abnormalities between January 1 and June 30, 1998. Table 1 provides a comparison of patients by gender and age. All patients received both dual isotope perfusion (Tl 201 rest/Tc 99m sestamibi stress) tests and a gated acquisition (wall motion) study. Data were collected based on a retrospective analysis of patients' rest and stress gated acquisition studies.
Table 1
Comparison of Patient Gender and Age

            Average Age   N < 50 Years

Men         64.15 years   29 (10%)
(n = 291)

Women       62.23 years   19 (10%)
(n = 184)


Evaluation of each patient included a perfusion thallium rest test followed by stress using a treadmill or administration of adenosine or persantine (dypridamole) and gated acquisition. The resting patient protocol called for an injection of 3.5 mCi (130 mBq) of Tl 201 with imaging performed on an Elscint SPX4 low-energy, high-resolution gamma camera system (Elscint Ltd, Rockleigh, NJ). Patients were in a supine position with arms extended overhead. Image acquisition required approximately 20 minutes. The camera and computer were set for a thallium window energy of 70 keV (15%) and 167 keV (10%) respectively. Images were acquired over a 180 [degrees] range starting at 45 [degrees] RAO) and ending at 45 [degrees] LPO. The computer acquired data in byte mode of 64 frame size, an angle step of 3 [degrees] and a frame time of 20 seconds in a clockwise direction.

The thallium rest test was followed either by stressing the patient on a treadmill or pharmacologically inducing stress if the patient was incapable of exercise. Patients capable of treadmill exercise followed a Bruce or Modified Bruce[18] protocol, which involved steps of increasing speed and elevation until the patient reached 85% of maximal heart rate or as high as the patient was capable. At peak, patients were injected with 25 mci (925 mBq) of Tc 99m sestamibi and continued on the treadmill for 1 minute postinjection.

Patients pharmacologically stressed by either adenosine or persantine (dipyridamole) were NPO for 4 hours prior to administration and discontinued persantine products for 24 hours. Contraindication for pharmacologically induced stress testing included 2% to 3% atrioventricular block, sinus node diseases, bronchospasm disease or severe chronic obstructive pulmonary disease.

Each patient's adenosine dose was calculated based on his or her weight in kilograms x 0.84 mg/kg. This dose was administered to patients in 50 ml of saline pumped through in a continuous volume over a 6-minute period. Patients were injected with 25 mCi (925 mBq) of Tc 99m sestamibi 3 minutes into the administration phase. Patients were monitored constantly for blood pressure changes throughout the 6minute period.

In cases where the cardiologist indicated a preference and for patients with low heart rates (less than 60 beats per minute), persantine (dipyridamole) was used as a pharmacological inducer. Dose calculation was based on patient weight in kilograms x 0.57mg/kg. The dose was administered through a continuous pump diluted in 45 to 50 ml of saline for 4 minutes, with a maximum dose of 60 mg. Blood pressure was monitored continuously during infusion. If a 10-point drop in the diastolic value was noted, patients were immediately injected with 25 mCi (925 mBq) of Tc 99m sestamibi. If no such drop was noted, patients were injected with radiopharmaceutical 8 minutes after the start of infusion. Imaging with the Elscint SPX4 gamma camera system began 30 minutes post Tc 99m sestamibi injection.

The procedure for imaging after stress testing by treadmill or pharmacologically induced methods included a 3-lead patient set-up, camera parameters based on a step-and-shoot gated acquisition and normal R wave displayed on the electrocardiogram. As data was gated to the R wave of the patient's ECG, a good signal was mandatory and efforts were made to obtain an optimal trigger before starting the test. Camera acquisition of data was based on a 10% window setting at approximately 140 kev energy, 8 frames/cycle, a frame size of 64, angle step of 3 [degrees] and step time of 20 seconds. Processing of data included normalization of raw data, background subtraction, alignment of the heart in the center of the image and outlining of the left ventricle. A bull's-eye 3-D image of the left ventricle was obtained, including a composite of the slices of the heart in 3 planes.

Computer-acquired rest images were compared side by side with the newly acquired stress images obtained starting at 45 [degrees] RAO and ending at 45 [degrees] LPO. A cardiologist evaluated the images and rendered a diagnosis based on comparison of rest/stress and gated myocardium motion in the horizontal long axis, vertical long axis and the short axis.

Evaluation criteria used by the cardiologist included patient history, pattern of blood perfusion to each portion of the heart, calculation and observation of cardiac ejection fraction and quality of wall motion on dynamic cine mode display. Based on these observations and comparisons, the cardiologist diagnosed normal myocardial perfusion, ischemic perfusion or myocardial infarction. (See Figs. 1-3.)

[Figures 1-3 ILLUSTRATION OMITTED]

A hard copy of the dictated report was placed in each patient's file. The authors then independently categorized each patient based on the specific terminology used in the cardiologist's report as either normal, ischemic (reversible defect) or infarcted (fixed defect). An independent health physics department faculty member also verified the data results.

Discussion and Results

The results demonstrate a strong relationship between the amount of damage to heart muscle (ischemia and infarctions) and abnormal cardiac wall motion. (See Tables 2 and 3.) They support the findings of Udelson et al[8] and Chua et al[9] in demonstrating increased specificity and sensitivity when a combined acquisition of gated wall motion and rest/stress perfusion imaging was used.

Table 2 Comparison of Perfusion and Gated Wall Motion Studies of Men (n = 291)
Perfusion Rest/Stress Test Results           Gated Wall Motion
                                                Study Results

                                            Abnormal Wall Motion
                                          (Hypokinesis or Akinesis,
                                                  n = 116)

Fixed defects; n = 22                             19 (86%)
Reversible defects; n = 129                       68 (53%)
Fixed and reversible defects; n = 30              29 (97%)
Normal perfusion; n = 110                             0

Perfusion Rest/Stress Test Results

                                             Normal Wall Motion
                                                  (n = 171)

Fixed defects; n = 22                              2 (9%)
Reversible defects; n = 129                       59 (46%)
Fixed and reversible defects; n = 30               1 (3%)
Normal perfusion; n = 110                         109 (99%)

Perfusion Rest/Stress Test Results

                                                 Nongated(*)
                                                   (n = 4)

Fixed defects; n = 22                              1 (5%)
Reversible defects; n = 129                        2 (1%)
Fixed and reversible defects; n = 30                  0
Normal perfusion; n = 110                          1 (1%)


(*) Nongated patients could not perform gated studies due to irregular heart rate or bradycardia.

Table 3 Comparison of Perfusion and Gated Wall Motion Studies of Women (n = 184)
Perfusion Rest/Stress Test Results          Gated Wall Motion
                                              Study Results

                                           Abnormal Wall Motion
                                        (Hypokinesis or Akinesis,
                                                 n = 28)

Fixed defects; n = 14                            10 (71%)
Reversible defects; n = 28                       13 (46%)
Fixed and reversible defects; n = 3              3 (100%)
Normal perfusion; n = 139                        2 (1.5%)

Perfusion Rest/Stress Test Results

                                            Normal Wall Motion
                                                (n = 154)

Fixed defects; n = 14                            4 (29%)
Reversible defects; n = 28                       15 (54%)
Fixed and reversible defects; n = 3                 0
Normal perfusion; n = 139                       135 (97%)

Perfusion Rest/Stress Test Results

                                               Nongated(*)
                                                 (n = 2)

Fixed defects; n = 14                               0
Reversible defects; n = 28                          0
Fixed and reversible defects; n = 3                 0
Normal perfusion; n = 139                        2 (1.5%)


(*) Nongated patients could not perform gated studies due to irregular heart rate or bradycardia.

In patients diagnosed with fixed defects (infarctions), 86% of men and 71% of women had abnormal gated studies (hypokinesis or akinesis wall motion). Male patients (n=30) who demonstrated both a fixed deflect (infarction) and a reversible defect (ischemia) had a 0.97 correlation to abnormal wall motion studies; female patients (n=3) showed a 1.0 correlation. Both male patients (99%) and female patients (97%) who demonstrated normal rest/stress perfusion tests were more likely to have normal gated cardiac wall motion results.

Patients diagnosed with reversible defects had nearly equal numbers of normal and abnormal gated wall motion studies. Male patients with reversible defects (n=129) showed a 0.53 correlation to gated abnormal cardiac wall motion assessment, while female patients (n=28) demonstrated a 0.46 correlation.

Major Gender Differences

The most surprising result was the difference in the percentage of women vs men who tested normal on the perfusion and gated studies. (See Table 4.) Seventy-six percent of female patients were found to be normal on perfusion and 84% were normal on gated acquisition. The percentages were significantly lower for males, with 38% demonstrating normal perfusion studies and 59% normal on gated testing.

Table 4 Normal Rates (Men vs Women)
                   Women (n = 184)    Men (n = 191)

Normal perfusion      139 (76%)        110 (38%)
studies

Normal gated          154 (84%)        171 (59%)
studies


The researchers attempted to find a causal effect for these large gender differences. Outcomes and variations in stress methodology, percentage of patients who reached 85% of maximal heart rate on treadmill testing and age differences were compared. The majority of men (75%) were stressed by treadmill exercise. However, this variable did not seem to influence the overall tendency for a much lower normal rate for men as 39% undergoing treadmill exercise were normal compared to 33% of those who were pharmacologically stressed. (See Table 5.)

Table 5 Stress Testing Method And Results in Men (n = 291)
Treadmill (n = 219, 75%)

Positive (ischemia or infarction)      133 (61%)
Negative (normal)                       86 (39%)

Pharmacologically induced stress
(n = 72, 31 adenosine, 41 persantine; 25%)

Positive (ischemia or infarction)       48 (67%)
Negative (normal)                       24 (33%)


A smaller percentage of women (51%) were stressed by treadmill testing, but again this did not seem to influence the overall normal rates. Of the women stressed on a treadmill, 85% were normal, while 66% were normal among those stressed pharmacologically. (See Table 6.) The overall normal rates for women were much higher than for men on both treadmill and pharmacologically induced stress.

Table 6 Stress Testing Method And Results in Women (n = 184)
Treadmill (n = 93, 51%)
Positive (ischemia or infarction)       14 (15%)
Negative (normal)                       79 (85%)

Pharmacologically induced stress
(n = 91, 30 adenosine, 61 persantine; 49%)

Positive (ischemia or infarction)       31 (34%)
Negative (normal)                       60 (66%)


Because 66% of all patients were stressed by treadmill, the researchers investigated whether there was a cause and effect relationship with higher reported normal rates in perfusion and gated studies in women related to their ability to reach 85% of maximal heart rate on treadmill exercise. There was almost no difference in the overall percentage, as 74% of women and 75% of men were able to achieve at least 85% of maximal heart rate from treadmill exercise. (See Table 7.)

Table 7 Ability to Reach 85% of Maximum Expected Heart Rate, Comparison of Men vs Women
            Achieved More Than   Achieved Less Than
             35% of Expected      85% of Expected
                Heart Rate           Heart Rate

Men             164 (75%)             55 (25%)
(n = 219)

Women            69 (74%)             24 (26%)
(n = 93)


Finally, researchers evaluated age as a variable between men and women and the percentage of patients who were younger than 50 years of age. Fifty years and younger was selected because this is the reported median age at which women begin menopause.[19] There is a tremendous amount of research relating menopause and the onset of CAD in women. Following menopause, the decline in the concentration of high-density lipoproteins (HDL) is thought to contribute to the increasing incidence of CAD[20-21] and the mortality rates from CAD in women nearly equal those of men.[22] There was little difference between male and female patients in age. The average age of the men was 64.1 years (range = 34 to 89); the average age of the women was 62.2 years (range = 33 to 97), as reported in Table 1. Only 10% of the male patients and 10% of the female patients were younger than 50 years of age. Therefore, age did not seem to influence women's higher normal rates on perfusion or gated studies.

Limitations of the Study

This study was limited to the patient population at the subject outpatient diagnostic facility in the time frame studied. Generalization of results beyond the sample must be made with caution. The data collected and recorded over the 6-month evaluation period may not have been adequate to determine a cause and effect relationship between higher normal levels in women as compared to men. Evaluation of additional variables such as patient weight, preliminary diagnosis and specific abnormality location within the heart may have been helpful. Accurate interpretation of data by the authors may have limited the study.

Conclusion

A high correlation between patients with fixed defects (infarctions) and abnormal gated myocardial motion (akinesis or hypokinesis) was found. Patients with normal perfusion testing results correlated highly with normal cardiac muscle motion results in gated studies. Approximately one half of ischemic patients demonstrated abnormalities in cardiac wall motion assessment.

Major differences were demonstrated in regard to gender. The normal rate for women was much higher than for men in both perfusion (rest/stress) testing and gated (cardiac wall motion) tests. Based on data available from this study, no cause and effect could be demonstrated for this unusually high normal rate in female patients. In addition, no cause and effect relationship was demonstrated between the patients' ability to reach 85% of maximal heart rate or patient age and the higher normal rates in women. This study did not evaluate variables such as patient weight and preliminary diagnosis. Therefore, it is not possible to make inferences regarding cause and effect.

Future research is indicated to investigate gender differences in larger patient populations at a variety of nuclear cardiology centers and to assess other possible contributing factors.

References

[1.] Hachamovitch R, Berman D, Kiat H. Effective risk stratification using exercise myocardial perfusion SPECT in women: gender-related differences in prognostic nuclear testing. J Am Coll Cardiol. 1996;28:34-44.

[2.] Taillefer R, Laflamme L. Myocardial perfusion imaging with Tc-99m Tc-methoxy-isobutyl-isonitrile (MIBI): comparison of short and long time intervals between rest and stress injections: preliminary results. Eur J Nucl Med. 1988;13:515-22.

[3.] Berman D, Kiat H, Friedman J. Separate acquisition 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;22:1455-1464.

[4.] Destafano F, Merritt RK, Andra RF, Casper ML. Trends in nonfatal coronary heart disease in the United States. Arch Intern Med. 1993;153:2489-2494.

[5.] Iskandrian AS, Heo J, Kong B, Lyons E, Marsh S. Use of technetium-99m isonitrile in assessing left ventricular perfusion and function at rest and during exercise in coronary artery disease, and comparison with coronary arteriography and exercise in thallium 201 SPECT imaging. Am J Cardiol. 1989;64:270-275.

[6.] Marzullo P, Oberdan P, Reisenhofer B. Value of rest thallium-201/technetium-99m sestamibi scans and dobutamine echocardiography for detecting myocardial viability. Am J Cardiol. 1993;71:166-172.

[7.] Berman DS, Kiat H, Van Train KF. Comparison of SPECT using technetium-99m agents and thallium and PET for the assessment of myocardial perfusion and viability. Am J Cardiol. 1990;66:72E-79E.

[8.] Udelson J, Coleman P, Metherall J. Predicting recovery of severe regional ventricular dysfunction of resting scintigraphy with Tl-201 and Tc-99m-sestamibi. Circulation. 1994;89:2552-2561.

[9.] Chua T, Kiat H, Germano G. Technetium-99m sestamibi for simultaneous assessment of stress myocardial perfusion, post exercise regional ventricular function and myocardial viability. J Am Coll Cardiol. 1994;23:1107-1114.

[10.] Easer ED, Cheseboro JH, Sacks FM, Wenger NK, Whisnant JP, Winster M. American Heart Association medical/scientific statement on cardiovascular disease in women. Circulation. 1993;88:1999-2009.

[11.] Steingart RM, Packer M, Hamm P, Cogliane M. Sex differences in the management of coronary artery disease. Survival and ventricular enlargement investigators. N Engl J Med. 1991;325:226-305.

[12.] Taillefer R, Gordon D, Udelson J, Beller G. Comparing diagnostic accuracy of Tl-201 and Tc-99m sestamibi SPECT imaging (Perfusion and ECG gated SPECT) in detecting coronary artery disease in women. J Am Coll Cardiol. 1997;29:69-77.

[13.] Wenger NK. Coronary heart disease: diagnostic decision making. In: Douglas PS, ed. Cardiovascular Health and Disease in Women. Philadelphia, Pa: WB Saunders; 1993:25-42.

[14.] Wackers F. Diagnostic pitfalls of myocardial perfusion imaging in women. Journal of Myocardial Ischemia. 1992;4(10):23-37.

[15.] Zarate AO. International Mortality Chartbook: Levels and Trends, 1955-93. Hyattsville, Md: Health Services; 1994.

[16.] Shaw L, Miller D, Romesis J, Kargi D. Gender differences in noninvasive evaluation and management of patients with suspected coronary artery disease. Ann Intern Med. 1994;120:559-566.

[17.] Cerqueria MD. Diagnostic testing strategies for coronary artery disease: special issues related to gender. Am J Cardiol. 1995;75:52D-60D.

[18.] Bruce RA. Exercise testing of patients with coronary artery disease. Am Clin Res. 1971;3:323-332.

[19.] Fauci A, Braunwald E. Harrison's Principles of Internal Medicine. 14th ed. Philadelphia, Pa: McGraw-Hill; 1997:2102.

[20.] Chemnitius JM, Winkel H. Age related decrease of high density lipoproteins in women after menopause. Medizinische-Klinik. 1998;93:137-145.

[21.] LaCharity L. The experiences of postmenopausal women with coronary artery disease. Western Journal of Nursing Research. 1997;19:583-602; discussion 602-7.

[22.] Redberg R. Coronary artery disease in women: understanding the diagnostic and management pitfalls. Available at: http://webspirs.silverpl.

Art Meyers, Ed.D., R. T. (N), CNMT, is an associate professor in the Department of Health Physics, Nuclear Medicine Program, at the University of Nevada, Las Vegas.

James Ballow, B.S., R.T. (N), CNMT, is chief technologist and administrator at Advanced Heart Care in Las Vegas.

The authors thank Leo J. Spaccavento, M.D., FACC, board-certified nuclear cardiologist, for his diagnostic assessment of all studies in this research and his cooperation in making this project possible.

Reprint requests may be sent to the American Society of Radiologic Technologists, Communications Department, 15000 Central Ave. SE, Albuquerque, NM 87123-3917.

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Title Annotation:cardiology
Author:MEYERS, ART; BALLOW, JAMES
Publication:Radiologic Technology
Article Type:Statistical Data Included
Geographic Code:1USA
Date:Jul 1, 1999
Words:3571
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