Single photon emission computed tomography myocardial imaging: clinical applications and future directions.

Single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) has proven to be an invaluable tool in the non-invasive assessment of patients with cardiovascular diseases. Exercise and pharmacologic stress SPECT MPI has been extensively studied and validated in the diagnosis and prognosis of patients with known and suspected coronary artery disease. In addition to the assessment of perfusion, electrocardiography-gated SPECT offers additional functional and volumetric information that can have significant implications on patient care. SPECT also has well-developed applications in systolic heart failure for identifying viable myocardium and predicting response to revascularization. Emerging applications of SPECT imaging include: l) phase analysis for quantitative assessment of LV dyssynchrony that may serve to improve patient selection for CRT; 2) application of heart-to-mediastinal ratio via 123I meta-iodobenzylguanidine (I-MIBG) imaging for the prediction of sudden death in patients with reduced left ventricular function, that may serve to improve patient selection for ICD therapy, and 3) use of metabolic tracers to identify the changes of ''ischemic memory'', which may help with rapid and appropriate triage of patients in the emergency room setting. SPECT MPI remains a cornerstone of clinical care that is evolving with emerging and novel applications that will continue to improve the care of patients with cardiovascular disease in the future.

Measuring left ventricular mechanical dyssynchrony from ECG-gated SPECT myocardial perfusion imaging.

Cardiac resynchronization therapy (CRT) has shown benefits in patients with severe heart failure. The traditional criteria to select patients for CRT (New York Heart Association [NYHA] class III or IV, depressed left ventricular [LV] ejection fraction, and prolonged QRS duration) result in at least 30% of the selected patients with no response to CRT. Recent studies with echocardiography have shown that the presence of LV dyssynchrony is an important predictor for response to CRT. However, the recent report from the predictors of response to cardiac resynchronization therapy (PROSPECT) trial suggested that under ''real-world'' conditions the current available echocardiographic techniques including tissue Doppler imaging (TDI) and myocardial strain-rate imaging are not ready for routine clinical practice to assess LV dyssynchrony. Phase analysis is a recently developed technique that allows measuring LV dyssynchrony from electrocardiogram (ECG)-gated single photon emission computed tomography (GSPECT) myocardial perfusion imaging (MPI). This technique uses Fourier harmonic functions to approximate regional wall thickening over the cardiac cycle and to calculate regional onset of mechanical contraction (OMC) phases. These OMC phases are obtained three-dimensionally over the entire left ventricle to quantitatively assess the degree of LV dyssynchrony. This technique has been compared to TDI and shown promising results in clinical validations. The advantages of this technique over echocardiography in measuring LV dyssynchrony are its automation, its high repeatability and reproducibility. It can be applied to any conventional GSPECT MPI study with no additional procedure. In this review the phase analysis methodology is described and its up-to-date clinical validations are summarized.

Efficiency comparison between 99m Tc-tetrofosmin and 99m Tc-sestamibi myocardial perfusion studies.

The purpose of this investigation was to compare the efficiency of two different imaging protocols using two different clinically available 99mTc labelled myocardial perfusion tracers. One thousand one hundred and thirty-four imaging studies were performed prospectively, using either 99mTc-tetrofosmin or 99mTc-sestamibi, alternating the use of each tracer for a total period of 8 months. 99mTc-tetrofosmin rest studies were performed with injections of 259MBq-370MBq and imaging 30 min later. Exercise studies were performed with injections of 777MBq-1.11GBq and imaging 20 min later. 99mTc-sestamibi studies used doses similar to those in the 99mTc-tetrofosmin studies. Imaging followed a standard procedure, at 60 min after rest injection, and 30 min after exercise. For patients undergoing pharmacological stress testing99mTc-sestamibi was imaged 45 min after injection and 99mTc-tetrofosmin was imaged 30 min after injection. Variables analysed were (1) injection-to-imaging time for the procedure, and (2) the number of repeated scans because of extra cardiac activity. The completion time for the rest study was significantly shorter for 99mTc-tetrofosmin compared to 99mTc-sestamibi (47.7+/-21.7 min vs 74.3+/-25.8 min P<0.0001). Likewise, the total study time was shorter for 99mTc-tetrofosmin compared to 99mTc-sestamibi (90+/-32.7 min vs 124+/-37 min, P<0.0001). More importantly, the number of repeated scans was higher with 99mTc-sestamibi compared to 99mTc-tetrofosmin, 21.4% vs 10%, P=0.001 for rest studies and 16.4% vs 7.9% P=0.001 [corrected] for rest and stress. It was concluded that, using a same day rest/stress protocol, 99mTc-tetrofosmin provided higher patient throughput with fewer repeat scans. These factors may be considered for efficiency improvement in nuclear cardiology laboratories using 99mTc perfusion tracers.

Quantification of myocardial hypoperfusion with 99m Tc-sestamibi in patients undergoing prolonged coronary artery balloon occlusion.

Percutaneous transluminal coronary angioplasty provides an excellent opportunity to investigate the location and quantity of hypoperfusion during sudden complete occlusion of one of the major coronary arteries. Thirty-five patients referred for elective percutaneous transluminal coronary angioplasty were injected intravenously with 99mTc-sestamibi during balloon inflation. To visualize and quantify the hypoperfused region, a map of perfusion was constructed from that occlusion study and from the control study performed on the following day. Patients were divided into groups according to proximal or distal occlusion within each of the three coronary arteries. The region of myocardium supplied by each coronary artery varied in location and extended outside the typical borders for all arteries, but most prominently for the left circumflex coronary artery. The quantities of hypoperfusion varied within each artery group, but the average hypoperfusion was greater for the left anterior descending coronary artery than for either the right coronary artery or the left circumflex coronary artery. It is concluded that the quantities of hypoperfusion were highly variable within each artery group. Occlusion of the left anterior descending coronary artery was associated with the largest ischaemic region. The area of hypoperfusion extended outside the typical borders, most prominently for the left circumflex coronary artery.

Incremental prognostic value of RNA ejection fraction measurements during pharmacologic stress testing: a comparison with clinical and perfusion variables.

UNLABELLED: This investigation examined the prognostic power of first-pass radionuclide angiocardiography (RNA) ejection fraction compared with clinical information and myocardial perfusion imaging in patients undergoing pharmacologic stress testing. The value of RNA and myocardial perfusion imaging in predicting death or nonfatal myocardial infarction (MI) is well established. However, limited information exists on the usefulness of combined myocardial perfusion imaging and RNA to predict prognosis, especially in patients undergoing pharmacologic stress testing. METHODS: We identified 240 patients who underwent pharmacologic stress testing with myocardial perfusion imaging and combined RNA. The patients were followed for a mean of 1.4 y. Cox proportional hazards models were used to assess the value in predicting death and MI. Multivariable models were generated to assess the independent incremental predictive value of clinical and nuclear imaging variables. Kaplan-Meier survival and event-free survival estimates were examined in patients with low (< or = 45%) versus high (>45%) ejection fractions. RESULTS: Clinical information, myocardial perfusion imaging, and RNA ejection fraction were significant predictors of the death/MI composite outcome (chi(2) = 7.4, 14.0, and 21.8, respectively). The addition of myocardial perfusion imaging to the clinical information provided incremental prognostic information (chi(2) = 15.2). The addition of RNA ejection fraction provided further predictive information (chi(2) = 22.5). However, when RNA ejection fraction was first added to the clinical information, myocardial perfusion imaging had no incremental prognostic value. CONCLUSION: For hard cardiac events, RNA ejection fraction provides prognostic information besides that provided by clinical and myocardial perfusion imaging. In patients who cannot exercise and are undergoing noninvasive evaluation with pharmacologic stress testing and myocardial perfusion imaging, ejection fraction should be measured simultaneously for risk assessment optimization.

Cardiac perfusion changes in patients treated for breast cancer with radiation therapy and doxorubicin: preliminary results.

PURPOSE: To determine the incidence and dose dependence of regional cardiac perfusion abnormalities in patients with left-sided breast cancer treated with radiation therapy (RT) with and without doxorubicin (Dox). METHODS: Twenty patients with left-sided breast cancer underwent cardiac perfusion imaging using single photon emission computed tomography (SPECT) prechemotherapy, pre-RT, and 6 months post-RT. SPECT perfusion images were registered onto 3-dimensional (3D) RT dose distributions. The volume of heart in the RT field was quantified, and the regional RT dose was calculated. A decrease in regional cardiac perfusion was assessed subjectively by visual inspection and objectively using image fusion software. Ten patients received Dox-based chemotherapy (total dose 120-300 mg/m(2)), and 10 patients had no chemotherapy. RT was delivered by tangent beams in all patients to a total dose of 46-50 Gy. RESULTS: Overall, 60% of the patients had new visible perfusion defects 6 months post-RT. A dose-dependent perfusion defect was seen at 6 months with minimal defect appreciated at 0-10 Gy, and a 20% decrease in regional perfusion at 41-50 Gy. One of 20 patients had a decrease in left ventricle ejection fraction (LVEF) of greater than 10% at 6 months; 2/20 patients had developed transient pericarditis. No instances of myocardial infarction or congestive heart failure (CHF) have occurred. CONCLUSIONS: RT causes cardiac perfusion defects 6 months post-RT in most patients. Long-term follow-up is needed to assess whether these perfusion changes are transient or permanent and to determine if these findings are associated with changes in overall cardiac function and clinical outcome.

Whole-body Tc-99m sestamibi scintigraphy in the follow-up of differentiated thyroid carcinoma.

PURPOSE: This study evaluated the potential of Tc-99m sestamibi whole-body scan (WBMIBI) as an alternative to whole-body I-131 scan (WBI) for the follow-up of patients with differentiated thyroid carcinoma. MATERIALS AND METHODS: We evaluated 99 consecutive patients with differentiated thyroid carcinoma who had total or nearly total thyroidectomy followed by an ablative dose of I-131 (86 women, 13 men; mean age, 44 +/- 12 years). WBMIBI was performed and serum thyroglobulin (TG) levels were obtained at least 6 months after I-131 treatment. All persons were receiving levothyroxine therapy. RESULTS: From the total of 110 studies performed, WBMIBI and TG were in agreement in 96% and discordant in 4%. From the 27 crossed studies (WBMIBI x TG) with at least one abnormal result, 16 were compared with WBI. In four cases, the WBI did not reveal functioning thyroid tissue when both TG and WBMIBI indicated tumoral activity. In one case of pulmonary metastasis confirmed by chest radiographs, with a normal TG value, the results of both WBMIBI and WBI were positive. CONCLUSIONS: WBMIBI should be considered as a scintigraphic method in the follow-up of differentiated thyroid carcinoma. This technique can show the sites of tumoral activity with optimal image resolution, particularly in those with abnormal TG and negative WBI results, and it is a potentially valuable tool in patients with anti-TG antibodies. The WBI in patients having ablation should be reserved only for therapy planning.

Noninvasive strategies for the estimation of cardiac risk in stable chest pain patients. The Economics of Noninvasive Diagnosis (END) Study Group.

Effective allocation of medical resources in stable chest pain patients requires the accurate diagnosis of coronary artery disease and the stratification of future cardiac risk. We studied the relative predictive value for cardiac death of 3 commonly applied noninvasive strategies, clinical assessment, stress electrocardiography, and myocardial perfusion tomography, in a large, multicenter population of stable angina patients. The multicenter observational series comprised 7 community and academic medical centers and 8,411 stable chest pain patients. All patients underwent pretest clinical screening followed by stress (exercise 84% or pharmacologic 16%) electrocardiography and myocardial perfusion tomography. Risk-adjusted multivariable Cox proportional hazards models were developed to predict cardiac death. Kaplan-Meier rates of time to cardiac catheterization were also computed. Cardiac mortality was 3% during the 2.5 +/- 1.5 years of follow-up. The number of infarcted vascular territories and pretest clinical risk factors were strong predictors of cardiac mortality, whereas the number of ischemic vascular territories gained increasing importance when determining post-test resource use requirements (i.e., the decision to perform cardiac catheterization). Exertional ST-segment depression in a population with a high frequency of electrocardiographic abnormalities at rest was not a significant differentiator of cardiac death risk. Stable chest pain patients are accurately identified as being at high risk for near-term cardiac events by both physicians' screening clinical evaluation and by the results of stress myocardial perfusion imaging. Disease management strategies for stable chest pain patients aimed at risk reduction should incorporate knowledge of relevant end points in treatment and guideline development.

Poststress measurements of left ventricular function with gated perfusion SPECT: comparison with resting measurements by using a same-day perfusion-function protocol.

PURPOSE: To investigate the relationship between the development of ischemia during stress testing and the changes in left ventricular ejection fraction (LVEF) measurements obtained after stress and at rest with a same-day perfusion-function imaging protocol. MATERIALS AND METHODS: One hundred twenty-six patients underwent a same-day rest-stress (61%) or stress-rest (39%) protocol and gated single photon emission computed tomography (SPECT). Perfusion analysis was performed with a 12-segment model. Defects were scored (0 = no defect, 1 = mild defect, 2 = moderate defect, and 3 = severe defect); differences between the summed stress and resting scores of greater than three indicated substantial ischemia. RESULTS: Resting and poststress LVEFs correlated significantly (r = 0.97, P <.001); however, patients with and patients without ischemia had significant differences in poststress versus resting LVEFs (-4.0 vs 1.0, respectively; P <.01). In patients with ischemia versus patients without ischemia, subgroup analysis stress-rest (-2.5 vs 1.0, P =.047) and rest-stress (-4.0 vs 1.0, P =.006) protocols yielded similar results. CONCLUSION: In patients with clinically important stress-induced perfusion abnormalities, the LVEF after stress was significantly lower than the LVEF at rest with same-day rest-stress and stress-rest imaging protocols. In the clinical setting, poststress LVEFs may be lower than true resting measurements, particularly in patients with moderate to severe stress-induced ischemia.

Complementary nature of radiotracer parathyroid imaging and intraoperative parathyroid hormone assays in the surgical management of primary hyperparathyroid disease: case report and review.

PURPOSE: This article illustrates the complementary nature of preoperative radionuclide parathyroid imaging and intraoperative rapid parathyroid hormone (PTH) assays in primary hyperparathyroid disease. The authors review the literature on these procedures and compare this protocol and its cost-effectiveness with those of the classic four-gland exploration. MATERIALS AND METHODS: Preoperative parathyroid imaging with Tc-99m MIBI and intraoperative rapid PTH assays were performed at the time of neck exploration. RESULTS: One of two parathyroid adenomas seen on radionuclide images would have been missed if the authors had relied solely on the initial decrease in PTH assay value to a normal level. CONCLUSIONS: Tc-99m MIBI imaging and intraoperative rapid PTH assays are complementary; when used together, they lessen the likelihood that abnormal parathyroid glands will be overlooked. This experience and that of others suggest these combined procedures are cost-effective.

Prediction of myocardial perfusion abnormalities by quantitative regional function using a radionuclide angiography database: a comparison with wall motion analysis.

PURPOSE: Myocardial perfusion and functional information during the same study is now feasible. A new assessment of regional ejection fraction at rest and peak exercise by first-pass radionuclide angiography using a "normal" database file has been developed. OBJECTIVE: This study was performed to assess the relation between this new method of quantitative regional ejection fraction and myocardial perfusion abnormalities and to compare this new technique with visual analysis of regional wall motion. METHODS: Consecutive patients (n = 126) with simultaneous first-pass radionuclide angiography and perfusion SPECT imaging were studied at rest and peak exercise using a same-day protocol. The area under the receiver-operator characteristic curve (C index) was used to assess the concordance probability between perfusion and functional measurements, and logistic regression models were used to examine the ability of functional variables to predict perfusion results. RESULTS: A high concordance was found between the visual analysis of wall motion and perfusion abnormalities (C index = 0.796), and also between regional ejection fraction and perfusion defects (C index = 0.784). The maximal predictive power of functional variables was obtained by combining wall motion analysis and regional ejection fraction (C index = 0.859). Regional ejection fraction contributed, with 20% more information than provided by wall motion analysis alone (chi2 = 9.2, P = 0.0025). CONCLUSIONS: Quantitative regional ejection fraction using a normal database file has a strong relation to perfusion abnormalities and provides incremental information to regional wall motion analysis for predicting perfusion abnormalities. This new technique should be regarded as a potential adjunct to functional studies to evaluate patients with ischemic heart disease.

27. PET Image Interpretation. Attenuation-Corrected (ATN) Vs Non-Attenuation Corrected (NATN) Images.

Purpose: The purpose of this study was to evaluate the difference, if any, in lesion detection in ATN and NATN images.Methods: Sixty-one consecutive patients having clinical whole body FDG PET scans for oncologic indications were included. The patients were administered 10-20 mCi FDG intravenously, and imaging on the Advance (GE Medical Systems) was started 45 min-1 h after injection. The emission images were acquired for 4 min and the transmission images for 3 min per bed position. The images were reviewed on the vendor-provided workstation. Four of the interpreting physicians read the ATN images first, and the other read the NATN images first. The interpreting physicians were asked to determine if any lesions were seen on only the ATN or NATN images (discordant findings) and to describe differences in the images not affecting overall interpretation.Results: In the 61 patients, 3 discordant findings with abnormalities on the ATN images but not on the NATN images included the following: lung nodule, AP window node, and small para-aortic node. Observations that did not affect overall interpretation include the following: transmission scan helped localize lesion to be below instead of above the diaphragm; AT-N image better demonstrated liver metastasis; benign lung lesion seen only on ATN image (3 cases); pretracheal node seen better on NATN images; and low grade hilar activity on NATN not seen on ATN images.Conclusion: These results demonstrate that the ATN images detect more lesions than the NATN images, and that reviewing NATN images may not be necessary. A different method for performing this evaluation is now being undertaken.

The added value of simultaneous myocardial perfusion and left ventricular function.

The focus of this review is the advantages of simultaneously assessing myocardial perfusion and left ventricular function. Nuclear cardiology imaging techniques as well as the development of technetium-labeled perfusion tracers now permit combined myocardial-perfusion and left-ventricular function studies at a single testing interval. Radionuclide angiography as well as electrocardiographic-gated images of the perfused myocardium are the two well-established techniques for that purpose with a single injection of a technetium-labeled perfusion tracer. Recent data have demonstrated the impact and clinical role of these studies, when combined, in the diagnosis as well as prognosis and risk stratification of patients with suspected or known coronary artery disease. The addition of functional information to perfusion data has shown to improve the detection of multivessel disease. Most recent data have also demonstrated the ability of these combined measurements to improve the prediction of hard events. It appears that the role of each of these tests may differ, depending on the patient population, particularly in relation to gender and type of stress test performed. Finally, a third area of potential application of these combined techniques would be in the assessment of myocardial viability using pharmacologic stress tests in combination with wall-motion analysis by gated images of the perfused myocardium.

The noninvasive prediction of cardiac mortality in men and women with known or suspected coronary artery disease. Economics of Noninvasive Diagnosis (END) Study Group.

PURPOSE: The association between myocardial perfusion imaging defects and cardiac mortality in women is undefined. We examined whether myocardial perfusion imaging predicted cardiac mortality in men and women and compared this with other variables influencing prognosis. SUBJECTS AND METHODS: Six academic institutions with high-volume nuclear cardiology laboratories consecutively studied 5,009 men aged 62 +/- 12 years (mean ISD) and 3,402 women aged 66 +/- 11 years with symptomatic known or suspected coronary artery disease undergoing exercise (n = 7,486) or pharmacologic stress (n = 925) myocardial perfusion imaging. A pretest clinical risk index was calculated from age, history of myocardial infarction, diabetes, hypertension, and hypercholesterolemia. Myocardial perfusion images were analyzed for stress-induced defects or any defect in the territories of the three major coronary arteries. RESULTS: Stress-induced perfusion defects were seen in 39% of men and 25% of women (P = 0.0001). Extensive stress-induced or fixed defects (>2 vascular territories) were less common in women than men (10% vs 19%, and 4% vs 18%, both P = 0.0001). During a mean of 2.4 +/- 1.5 years of follow-up, 143 patients died of cardiac causes. The clinical risk index and number of territories with perfusion defects were associated with cardiac mortality in women and men. In women undergoing exercise myocardial perfusion imaging, the number of abnormal territories remained the strongest correlate of mortality after adjustment for exercise variables. CONCLUSIONS: The results of myocardial perfusion imaging are important, independent predictors of survival in both women and men.

The economic consequences of available diagnostic and prognostic strategies for the evaluation of stable angina patients: an observational assessment of the value of precatheterization ischemia. Economics of Noninvasive Diagnosis (END) Multicenter Study Group.

OBJECTIVES: The study aim was to determine observational differences in costs of care by the coronary disease diagnostic test modality. BACKGROUND: A number of diagnostic strategies are available with few data to compare the cost implications of the initial test choice. METHODS: We prospectively enrolled 11,372 consecutive stable angina patients who were referred for stress myocardial perfusion tomography or cardiac catheterization. Stress imaging patients were matched by their pretest clinical risk of coronary disease to a series of patients referred to cardiac catheterization. Composite 3-year costs of care were compared for two patients management strategies: 1) direct cardiac catheterization (aggressive) and 2) initial stress myocardial perfusion tomography and selective catheterization of high risk patients (conservative). Analysis of variance techniques were used to compare costs, adjusting for treatment propensity and pretest risk. RESULTS: Observational comparisons of aggressive as compared with conservative testing strategies reveal that costs of care were higher for direct cardiac catheterization in all clinical risk subsets (range: $2,878 to $4,579), as compared with stress myocardial perfusion imaging plus selective catheterization (range: $2,387 to $3,010, p < 0.0001). Coronary revascularization rates were higher for low, intermediate and high risk direct catheterization patients as compared with the initial stress perfusion imaging cohort (13% to 50%, p < 0.0001); cardiac death or myocardial infarction rates were similar (p > 0.20). CONCLUSIONS: Observational assessments reveal that stable chest pain patients who undergo a more aggressive diagnostic strategy have higher diagnostic costs and greater rates of intervention and follow-up costs. Cost differences may reflect a diminished necessity for resource consumption for patients with normal test results.

Combined Tc-99m sestamibi first-pass radionuclide angiography and cardiac SPECT imaging during arbutamine infusion delivered by a computerized closed-loop system.

PURPOSE: This study evaluated the feasibility, hemodynamic responses, and relation of combined Tc-99m sestamibi SPECT imaging and first-pass radionuclide angiography during the infusion of a new beta agonist arbutamine. METHODS: Arbutamine was administered to 15 patients and constantly adjusted by a closed-loop computerized system. Rest and arbutamine Tc-99m sestamibi radionuclide angiography was performed with a multicrystal gamma camera followed by SPECT imaging with a rotating triple-head, single-crystal gamma camera. RESULTS: The mean differences (paired t-test) between rest and arbutamine studies for heart rate (HR), end-diastolic volume (EDV), stroke volume (SV), cardiac output (CO), and ejection fraction (EF) were as follows: 55 bpm for HR (P < 0.001), 5 ml for EDV (P=ns), 7.5 ml for SV (P=0.04), 4.4 l/min for CO (P < 0.001), and 6.4% for EF (P < 0.001), respectively. The results of SPECT studies were abnormal in six patients and normal in nine. Findings of radionuclide angiography were normal in 12 patients and abnormal in three. Interpretation of the perfusion and functional studies were concordant in 10 and discordant in five patients. CONCLUSIONS: Simultaneous cardiac radionuclide angiography and SPECT imaging are feasible during arbutamine infusion. This potent beta agonist increases cardiac output through a chronotropic effect with no significant changes in EDV. The discordance in SPECT and radionuclide angiography results may represent incremental diagnostic and prognostic information provided by both studies.

Prognosis by measurements of left ventricular function during exercise. Duke Noninvasive Research Working Group.

UNLABELLED: This study was performed to determine whether gated equilibrium radionuclide angiogram measurements of left ventricular function during rest and exercise add independent information to clinical and catheterization data in predicting cardiac death. METHODS AND RESULTS: The study population consisted of 863 consecutive patients undergoing exercise gated equilibrium radionuclide angiography within 90 days of cardiac catheterization with data prospectively entered into the Duke Cardiovascular Database. All patients were symptomatic, medically treated, with significant coronary artery disease and had undergone follow-up for < or = 6 yr. A univariable and multivariable Cox regression analysis was utilized to evaluate the independent power in predicting 147 (17.0%) cardiac deaths. This risk-adjusted analysis revealed that only rest and exercise ejection fraction as well as maximum workload contained independent prognostic information; the nuclear variables contributed 63% of the total information within the model. A multivariable model including exercise ejection fraction and clinical history variables provided slightly more prognostic information than the combination of cardiac catheterization and clinical data. CONCLUSION: Multigated equilibrium radionuclide angiography is a key predictor of cardiac death when compared to clinical and cardiac catheterization data in patients with symptomatic, medically treated coronary artery disease. Thus, long-term outcome for patients may be determined by utilizing this noninvasive tool even when clinical and cardiac catheterization data are also available.