Hosen Kiat

Incremental Prognostic Value of Myocardial Perfusion Single Photon Emission Computed Tomography for the Prediction of Cardiac Death Differential Stratification for Risk of Cardiac Death and Myocardial Infarction

BACKGROUNDnThe incremental prognostic value of stress single photon emission computed tomography (SPECT) for the prediction of cardiac death as an individual end point and the implications for risk stratification are undefined.nnnMETHODS AND RESULTSnWe identified 5183 consecutive patients who underwent stress/rest SPECT and were followed up for the occurrence of cardiac death or myocardial infarction. Over a mean follow up of 642+/-226 days, 119 cardiac deaths and 158 myocardial infarctions occurred (3.0% cardiac death rate, 2.3% myocardial infarction rate). Patients with normal scans were at low risk (< or =0.5%/y), and rates of both outcomes increased significantly with worsening scan abnormalities. Patients who underwent exercise stress and had mildly abnormal scans had low rates of cardiac death but higher rates of myocardial infarction (0.7%/y versus 2.6%/y; P<.05). After adjustment for prescan information, scan results provided incremental prognostic value toward the prediction of cardiac death. The identification of patients at intermediate risk of nonfatal myocardial infarction and low risk for cardiac death by SPECT may result in significant cost savings when applied to a clinical testing strategy.nnnCONCLUSIONSnMyocardial perfusion SPECT yields incremental prognostic information toward the identification of cardiac death. Patients with mildly abnormal scans after exercise stress are at low risk for cardiac death but intermediate risk for nonfatal myocardial infarction and thus may benefit from a noninvasive strategy and may not require invasive management.

Incremental value of prognostic testing in patients with known or suspected ischemic heart disease: a basis for optimal utilization of exercise technetium-99m sestamibi myocardial perfusion single-photon emission computed tomography.

OBJECTIVESnThis study assessed the incremental prognostic implications of normal and equivocal exercise technetium-99m (Tc-99m) sestamibi single-photon emission computed tomography (SPECT) and sought to determine its incremental prognostic value, impact on patient management and cost implications.nnnBACKGROUNDnThe prognostic implications of Tc-99m sestamibi SPECT are not well defined, and risk stratification using this test has not been explored.nnnMETHODSnWe studied 1,702 patients referred for exercise Tc-99m sestamibi SPECT who were followed up for a mean (+/- SD) of 20 +/- 5 months. Patients with previous percutaneous transluminal coronary angioplasty or coronary artery bypass surgery were excluded. The SPECT studies were assessed using semiquantitative visual analysis. Cardiac death and myocardial infarction were considered hard events, and coronary angioplasty and bypass surgery > 60 days after testing were considered soft events.nnnRESULTSnOf the 1,702 patients studied, 1,131 had normal or equivocal scan results. A total of 10 events occurred in this group (1 cardiac death and 1 myocardial infarction [0.2% hard events]; 4 coronary angioplasty and 4 bypass surgery procedures [0.7% soft events]). The rates of hard events and referral to catheterization after SPECT were similarly low in patients with a low (< 0.15), intermediate (0.15 to 0.85) and high (> 0.85) post-exercise treadmill test (ETT) likelihood of coronary artery disease. With respect to scan type, patients with normal, probably normal or equivocal scan results had similarly low hard event rates. In the 571 patients with abnormal scan results, there were 43 hard events (7.5%) and 42 soft events (7.4%) (p < 0.001 vs. 1,131 patients with normal scan results for both). When the complete spectrum of scan responses was considered, SPECT provided incremental prognostic value in all patient subgroups analyzed. However, the nuclear scan was cost-effective only in patients with interpretable exercise ECG responses and an intermediate to high post-ETT likelihood of coronary artery disease and in those with uninterpretable exercise ECG responses and an intermediate to high pre-ETT likelihood of coronary artery disease.nnnCONCLUSIONSnNormal or equivocal exercise Tc-99m sestamibi study results are associated with a benign prognosis, even in patients with a high likelihood of coronary artery disease. Although incremental prognostic value is added by nuclear testing in all patient subgroups, a testing strategy incorporating nuclear testing proved to be cost-effective only in the groups with an intermediate to high likelihood of coronary artery disease before scanning.

Comparison of technetium 99m methoxy isobutyl isonitrile and thallium 201 for evaluation of coronary artery disease by planar and tomographic methods

To compare stress/rest technetium 99m methoxy isobutyl isonitrile (Tc-MIBI) with stress redistribution thallium 201(T1-201) myocardial perfusion imaging, 36 patients were studied by single photon emission computerized tomography (SPECT) and planar methods. For SPECT, overall sensitivities for identification of patients with coronary artery disease were 93% (14/15) by Tc-MIBI and 80% (12/15) by TI-201 (p = NS). For planar methods, overall sensitivities were 73% (11/15) by both TI-201 and Tc-MIBI. Overall specificity was 75% (3/4 patients with normal coronary arteries) for both tracers with SPECT and Tc-MIBI by planar imaging and was 50% for planar TI-201 (p = NS). The normalcy rates for overall identification of coronary artery disease were determined in 17 patients with a low likelihood of disease. For SPECT, normalcy rates were 100% by Tc-MIBI and 77% by TI-201 (p = NS). For planar, they were 94% by Tc-MIBI and 88% by TI-201 (p = NS). Vessel sensitivities in the 35 stenosed coronary arteries (greater than or equal to 50% stenosis) for SPECT were 87% by Tc-MIBI and 77% by TI-201 (p = NS). For planar, the vessel sensitivities were 60% by Tc-MIBI and 54% by TI-201 (p = NS). For both tracers, the SPECT vessel sensitivities were significantly higher (p less than 0.005) than planar vessel sensitivities. The vessel specificities in 22 coronary vessels with less than 50% stenosis were 86% by SPECT Tc-MIBI and TI-201, 80% by planar Tc-MIBI and 73% by planar TI-201 (p = NS, SPECT vs planar, Tc-MIBI vs TI-201). Regarding myocardial segmental agreement, for the presence of stress defects the agreement was 91% for the 720 SPECT segments and 95% for the 540 planar segments. For severity of stress defects based on semiquantitative visual scoring, the exact agreement was 87% for SPECT and 80% for planar. For the pattern of reversibility in myocardial segments with stress defects, the agreement was 97% for SPECT and 91% for planar. This study demonstrated that Tc-MIBI and TI-201 correlate well on both planar and SPECT images with respect to the identification of patients with coronary artery disease, identification of disease in individual coronary arteries, the presence and severity of perfusion defects, and the assessment of defect reversibility. Furthermore, SPECT Tc-MIBI was shown to be superior to planar Tc-MIBI for the identification of individual diseased vessels.

Gated Technetium-99m Sestamibi for Simultaneous Assessment of Stress Myocardial Perfusion, Postexercise Regional Ventricular Function and Myocardial Viability: Correlation with Echocardiography and Rest Thallium-201 Scintigraphy

OBJECTIVESnThis study compares technetium-99m sestamibi (sestamibi) electrocardiographic (ECG) gated single-photon emission computed tomography (gated SPECT) and echocardiography for the evaluation of myocardial function and assesses the feasibility of single-injection, single-acquisition stress perfusion/rest function technetium-99m sestamibi-gated SPECT as an alternative to conventional stress/rest imaging for assessment of myocardial perfusion and viability.nnnBACKGROUNDnSimultaneous assessment of stress perfusion and rest function is possible with gated SPECT acquisition of stress-injected technetium-99m sestamibi.nnnMETHODSnRest thallium-201 SPECT followed by stress sestamibi-gated SPECT (acquired 0.5 to 1 h after sestamibi injection) was performed in 58 patients. Echocardiography was performed immediately after or before gated SPECT in 43 of the patients. All studies were analyzed by semiquantitative visual scoring. Sestamibi-gated SPECT studies were read for stress perfusion and rest wall motion and thickening. Reversibility on sestamibi-gated SPECT was defined as the presence of a definite stress defect with normal or mildly impaired wall motion or thickening on gated SPECT:nnnRESULTSnThere was high segmental score agreement between gated SPECT and echocardiography for wall motion (91%, kappa = 0.68, p < 0.001) and thickening (90%, kappa = 0.62, p < 0.001). Correlation for global wall motion (r = 0.98, p < 0.001) and thickening (r = 0.96, p < 0.001) scores between the two modalities was excellent. In 32 patients without previous myocardial infarction, there was excellent agreement for reversibility between stress sestamibi-gated SPECT and rest thallium-201/stress sestamibi (98%, kappa = 0.93, p < 0.01). However, in 26 patients with previous infarction, discordance between the two approaches was frequent, with 26% (20 of 78) of nonreversible defects by stress sestamibi-gated SPECT being reversible by rest thallium-201/stress sestamibi and 21% (23 of 112) of reversible defects by stress sestamibi-gated SPECT being nonreversible by rest thallium-201/stress sestamibi.nnnCONCLUSIONSnGated SPECT of stress-injected sestamibi correlates well with echocardiographic assessment of regional function and thus adds information to perfusion SPECT: In patients without previous myocardial infarction, a single-injection stress perfusion/rest function approach using sestamibi-gated SPECT can substitute for conventional stress/rest myocardial perfusion imaging, adding a rest perfusion study only if there are nonreversible defects or consideration of attenuation artifacts. In patients with previous myocardial infarction, the gated SPECT approach does not replace the need for a rest perfusion study.

Identification of severe and extensive coronary artery disease by automatic measurement of transient ischemic dilation of the left ventricle in dual-isotope myocardial perfusion SPECT☆

OBJECTIVESnThis study sought to assess whether a transient ischemic dilation ratio, determined from automatically derived stress and rest left ventricular volumes during stress technetium-99m (Tc-99m) sestamibi/rest thallium-201 dual-isotope myocardial perfusion single-photon emission computed tomography (SPECT), is useful for the identification of patients with severe and extensive coronary artery disease.nnnBACKGROUNDnTransient ischemic dilation of the left ventricle on stress/redistribution thallium-201 scintigraphy has been shown to be a clinically useful marker of severe and extensive coronary artery disease. However, in practice, its assessment is highly subjective. This study automatically assessed the transient ischemic dilation ratio on the basis of a previously described algorithm to estimate three-dimensional ventricular boundaries.nnnMETHODSnNormal limits for the transient ischemic dilation ratio were developed using data from 54 patients with a low likelihood (< 5%) of coronary artery disease, and criteria for abnormality were developed based on data from 97 who under-went catheterization, of whom 34 had severe and extensive coronary artery disease, defined as > or = 90% stenosis in the proximal left anterior descending coronary artery or in two or more coronary arteries, and 63 had no coronary artery disease (15 patients) or mild to moderate coronary artery disease (48 patients). The criteria were then tested in a validation cohort of 77 additional patients who underwent catheterization, of whom 36 had severe and extensive coronary artery disease. The quantitative results of the dilation ratio were compared with the visual results of the dilation ratio and perfusion defect analysis.nnnRESULTSnFor normal limits, receiver operating characteristic curve analysis showed that abnormal transient ischemic dilation ratio values corresponded to left ventricular endocardial volume ratios > 1.22 (mean +/- 2 SD). Transient ischemic dilation assessment using these criteria for abnormality showed high sensitivity (24 [71%] of 34) and very high specificity (60 [95%] of 63) for severe and extensive coronary artery disease. When the analysis was applied to the prospective catheterization group, similar sensitivity and specificity for severe and extensive coronary artery disease were observed (77% and 92%, respectively). Significant agreement (p = 0.0001) was found between the degree of transient ischemic dilation and the Tc-99m sestamibi defect extent, the latter assessed by semiquantitative visual analysis (summed stress score).nnnCONCLUSIONSnThe automatic measurement of transient ischemic dilation in dual-isotope myocardial perfusion SPECT is a clinically useful marker that is sensitive and highly specific for detection of severe and extensive coronary artery disease.

Effective risk stratification using exercise myocardial perfusion SPECT in women: Gender-related differences in prognostic nuclear testing

OBJECTIVESnThis study was designed to evaluate the incremental prognostic value over clinical and exercise variables of rest thallium-201/exercise technetium-99m sestamibi single-photon emission computed tomography (SPECT) in women compared with men and to determine whether this test can be used to effectively risk stratify patients of both genders.nnnBACKGROUNDnTo minimize the previously described gender-related bias in the evaluation of coronary artery disease in women, there is a need to identify a noninvasive testing strategy that is able to accurately and effectively risk stratify women.nnnMETHODSnWe identified 4,136 consecutive patients (2,742 men, 1,394 women) who underwent dual-isotope SPECT. The incremental value of nuclear testing was determined using both a stepwise Cox proportional hazards model and Kaplan-Meier survival analysis. Receiver operating characteristic curve analysis was performed to determine test discrimination for high risk patients in men and women.nnnRESULTSnThe patient population was followed up for 20 +/- 5 months for events (cardiac death or nonfatal myocardial infarction). During this time, 63 myocardial infarctions and 32 cardiac deaths occurred in the men, and 31 myocardial infarctions and 14 cardiac deaths occurred in the women. Nuclear testing significantly stratified both men and women irrespective of their rest electrocardiogram. Cox proportional hazards analysis revealed that nuclear testing added incremental prognostic value in both men and women after inclusion of the most predictive clinical exercise variables (overall chi-square 89 in men vs. 120 in women, p < 0.005). Kaplan-Meier survival analysis demonstrated that nuclear testing further stratified men and women with both intermediate to high and low prescan likelihoods of coronary artery disease (p < 0.005 for all). Receiver operating characteristic curve analysis demonstrated superior discrimination for the nuclear scan results in identifying high risk women than men (area under the curve: 0.84 +/- 0.03 vs 0.71 +/- 0.03 in men, p < 0005). The odds ratio comparing event rates in patients with women than in men, suggesting superior stratification using nuclear testing in women.nnnCONCLUSIONSnDual-isotope myocardial perfusion imaging yields incremental prognostic value in both men and women. This modality identifies low risk women and men equally well but relatively high risk women more accurately than relatively high risk men and, thus, is able to stratify women more effectively than men.

Myocardial perfusion imaging with technetium-99m sestamibi SPECT in the evaluation of coronary artery disease

Technetium-99m (Tc-99m) sestamibi is a new myocardial perfusion imaging agent that offers significant advantages over thallium-201 (Tl-201) for myocardial perfusion imaging. The results of the current clinical trials using acquisition and processing parameters similar to those for Tl-201 and a separate (2-day) injection protocol suggest that Tc-99m sestamibi and Tl-201 single photon emission computed tomography (SPECT) provide similar information with respect to detection of myocardial perfusion defects, assessment of the pattern of defect reversibility, overall detection of coronary artery disease (CAD) and detection of disease in individual coronary arteries. Tc-99m sestamibi SPECT appears to be superior to Tc-99m sestamibi planar imaging because the former provides a higher defect contrast and is more accurate for detection of disease in individual coronary arteries. Research is currently under way addressing optimization of acquisition and processing of Tc-99m sestamibi studies and development of quantitative algorithms for detection and localization of CAD and sizing of transmural and nontransmural myocardial perfusion defects. It is expected that with the implementation of the final results of these new developments, further significant improvement in image quality will be attained, which in turn will further increase the confidence in image interpretation. Development of algorithms for analysis of end-diastolic myocardial images may allow better evaluation of small and nontransmural myocardial defects. Furthermore, gated studies may provide valuable information with respect to regional myocardial wall motion and wall thickening. With the implementation of algorithms for attenuation and scatter correction, the overall specificity of Tc-99m sestamibi SPECT should improve significantly because of a substantial decrease in the occurrence of attenuation-related image artifacts.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine technetium-99m sestamibi myocardial perfusion SPECT in women: Diagnostic efficacy in detection of coronary artery disease☆

OBJECTIVESnThis study sought to assess the diagnostic efficacy of adenosine technetium-99m sestamibi myocardial perfusion single-photon emission computed tomography (SPECT) in a consecutive series of female patients.nnnBACKGROUNDnThe utility of adenosine myocardial perfusion SPECT for the detection of coronary artery disease is not well defined in women because most studies have described a predominantly male population with a high prevalence of coronary artery disease.nnnMETHODSnOf the 201 consecutive female patients in the study group who had undergone adenosine Tc-99m sestamibi myocardial perfusion SPECT, 130 had coronary angiography within 2 months of the nuclear test, and the other 71 had a low likelihood (<10%, mean [+/-SD] 5 +/- 3%) of coronary artery disease. The SPECT protocol used separate acquisition of rest thallium-201 and adenosine Tc-99m sestamibi and was visually analyzed in 20 segments with a semiquantitative five-point scoring system (0=normal; 4=absent uptake).nnnRESULTSnThe normalcy rate in patients with a low likelihood of coronary artery disease was 93% (66 of 71). Among the catheterized group, the overall sensitivity, specificity and predictive accuracy of adenosine sestamibi SPECT for detecting coronary artery disease (> or = to 50% diameter stenosis) were 93% (87 of 94), 78% (28 of 36) and 88% (115 of 130), respectively. In the 103 patients without a prior myocardial infarction, the sensitivity, specificity and predictive accuracy were 91% (61 of 67), 78% (28 of 36) and 86% (89 of 103), respectively, for detecting > or = to 50% diameter stenosis. Of particular interest, the sensitivity and specificity were as high in patients with nonanginal symptoms (93% and 69%, respectively) as in patients with angina (92% and 83%, respectively, p=NS). The sensitivity and specificity among patients with a relatively low (<25%), intermediate (between 25% and 75%) or high prescan likelihood of coronary artery disease (>75%) were similar: 82% and 82%, 93% and 73%, and 95% and 100%, respectively. The sensitivity and specificity for detecting individual diseased vessels (> or = to 50% diameter stenosis) were, respectively, 76% and 81% for the left anterior descending coronary artery, 44% and 90% for the left circumflex coronary artery and 75% and 77% for the right coronary artery.nnnCONCLUSIONSnAdenosine Tc-99m sestamibi SPECT is an efficient protocol with high sensitivity and specificity for the detection of coronary artery disease in women irrespective of presenting symptoms or pretest likelihood of coronary artery disease and a high normalcy rate. These findings are of particular clinical relevance because chest pain, anginal or otherwise, has been shown to be a frequent but a less specific marker for coronary artery disease among female patients.

Gender-related differences in clinical management after exercise nuclear testing

OBJECTIVESnThis study sought to determine the rate of referral to cardiac catheterization in men and women early after nuclear testing as a function of the magnitude of myocardial ischemia by radionuclide perfusion imaging.nnnBACKGROUNDnAlthough many previous studies have suggested that gender-related differences are present in the clinical management of coronary artery disease, the presence of such a difference with respect to referral to catheterization after noninvasive testing is disputed.nnnMETHODSnWe examined 3,211 consecutive patients (1,074 women, 2,137 men) who underwent exercise dual-isotope single-photon emission computed tomography and had follow-up evaluation performed at least 1 year after nuclear testing (mean [+/- SD] follow-up 19 +/- 5 months) for hard events (cardiac death and myocardial infarction) and referral to cardiac catheterization or revascularization within 60 days of nuclear testing. Multiple logistic regression analysis was performed to determine the best predictors of referral to catheterization as well as to examine whether gender itself added further information to this model.nnnRESULTSnAlthough men were referred to catheterization more frequently than women (10.6% vs 7.1%, p < 0.001) early after exercise nuclear testing, there were no differences in the rate of referral to catheterization or revascularization after stratification by the amount of abnormally perfused myocardium detected by the nuclear scan. Both men and women with normal scan results were infrequently referred to subsequent catheterization. In the setting of severe ischemia, women were referred to catheterization more frequently than men. This higher rate appears to be clinically appropriate because women with severely abnormal scan results had a significantly higher event rate than men (17.5% vs. 6.3%, p < 0.0001). This greater risk in women than in men appeared to be underappreciated because the increased rate of hard events in women with severely abnormal scan results was out of proportion to the smaller increase in their rate of referral to cardiac catheterization. Although gender added information to the multivariate model most predictive of referral to catheterization models when nuclear variables were not included, when nuclear variables were considered, the addition of gender added no further significant information. This finding suggests that adjusting for differences in perfusion scan abnormalities by the use of nuclear testing eliminated the apparent gender-related referral bias.nnnCONCLUSIONSnAfter controlling for differences in perfusion scan abnormalities, no gender-related referral bias to catheterization was present. In the setting of severe ischemia, women had a greater rate referral to catheterization than men. As a function of risk, both men and women were appropriately referred to catheterization at a low rate when the scan result was normal. However, because women with severe perfusion abnormalities had a greater rate of cardiac death and myocardial infarction then men, women in this high risk subgroup were underreferred to catheterization relative to men. This finding points to the need to better identify women at high cardiac risk.

Identification of severe or extensive coronary artery disease in women by adenosine technetium-99m sestamibi SPECT

To assess the ability of adenosine technetium-99m sestamibi myocardial perfusion single-photon emission computed tomography (SPECT) to identify high-risk women with severe or extensive coronary artery disease (CAD), we studied 130 consecutive women who underwent adenosine sestamibi myocardial perfusion SPECT and catheterization within 2 months. Severe (> or = 50% stenosis of left main coronary artery, > or = 90% stenosis in the proximal left anterior descending or in > or = 2 coronary arteries) or extensive (> or = 70% stenosis in 3 vessels) CAD was present in 54 patients, whereas 76 had no CAD or mild to moderate CAD. Semiquantitative visual SPECT analysis used 20 segments and a 5-point scoring system (0 = normal, 4 = absent uptake). Among the clinical, hemodynamic and nuclear variables analyzed, univariate predictors of severe or extensive CAD included a higher prescan likelihood of CAD, history of myocardial infarction, a higher heart rate at rest, a lower increase in heart rate during adenosine infusion, a higher summed stress score, summed reversibility score, and multivessel scan abnormality. Multivariate logistic analysis of the most predictive clinical (prescan likelihood of CAD), hemodynamic (increase in heart rate during adenosine infusion), and scan variables (summed stress score) revealed summed stress score (chi-square = 32; p <0.0001) and prescan likelihood of CAD (chi-square = 6.4; p <0.05) as the only independent predictors of severe or extensive CAD. Based on these logistic models, we determined the probability for the presence of severe or extensive CAD in patients with low, intermediate, and high prescan likelihood of CAD across the range of values of a summed stress score. This revealed that there were incremental increases in the probability for severe or extensive CAD both as a function of prescan likelihood of CAD and summed stress score. A severely abnormal scan (summed stress score > 8) during adenosine technetium-99m sestamibi myocardial perfusion SPECT had a high sensitivity of 91% and a moderately high specificity of 70% for identifying high-risk women with severe or extensive CAD. These results coupled with the previously defined prognostic significance of these findings suggest this test to be a useful diagnostic tool for the evaluation of CAD in women.