Quantification of myocardial flow reserve using a gamma camera with solid-state cadmium-zinc-telluride detectors: Relation to angiographic coronary artery disease.

BACKGROUND: Previous studies have suggested using gamma cameras with cadmium-zinc-telluride (CZT) detectors to quantify myocardial blood flow (MBF) and flow reserve (MFR). In this study, we aimed to evaluate the feasibility and accuracy of MFR quantification using a CZT camera compared to coronary angiography. METHODS: Forty-one participants referred for coronary angiography underwent a rest/stress one-day myocardial perfusion imaging protocol using a CZT gamma camera. Rest and stress dynamic phases were followed by acquisition of traditional perfusion images and time-activity curves were generated. Angiographic and perfusion results were compared to MFR. RESULTS: Patients with abnormal perfusion presented reduced MFR (2.01 [1.48-2.77] vs. 2.94 [2.38-3.64], P = 0.002), and reduced stress MBF. Patients with high-risk CAD had lower global MFR compared to patients without obstructive disease (1.99 [1.22-2.84] vs. 2.89 [2.22-3.58], P = 0.026). Obstructed vessels showed lower regional MFR when compared to non-obstructed (1.81 [1.19-2.67] vs. 2.75 [2.13-3.42], P < 0.001). A regional MFR of 2.2 provided a sensitivity of 63.2% and specificity of 74.1% to identify an obstructive lesion in the corresponding artery. CONCLUSION: In patients undergoing invasive coronary angiography for the evaluation of CAD, quantifying MBF and MFR in a CZT gamma camera is feasible and reflects underlying disease. In these patients, reduced regional MFR suggests the presence of obstructive lesion(s).

The additional prognostic value of myocardial perfusion SPECT in patients with known coronary artery disease with high exercise capacity.

BACKGROUND: The prognostic value of myocardial perfusion imaging (MPI) in patients with known coronary artery disease (CAD) and high exercise capacity is still unknown. We sought to determine the MPI additional prognostic value over electrocardiography (ECG) stress testing alone in patients with known CAD who achieved ≥ 10 metabolic equivalents (METs). METHODS AND RESULTS: We evaluated 926 patients with known CAD referred for MPI with exercise stress. Patients were followed for a mean of 32.4 ± 9.7 months for the occurrence of all-cause death or nonfatal myocardial infarction (MI). Those achieving ≥ 10 METs were younger, predominantly male, and had lower prevalence of cardiovascular risk factors. Patients reaching ≥ 10 METs had a lower annualized rate of hard events compared to their counterparts achieving < 10 METs (1.13%/year vs 3.95%/year, P < .001). Patients who achieved ≥ 10 METs with abnormal scans had a higher rate of hard events compared to those with normal scans (3.37%/year vs 0.57%/year, P = .023). Cardiac workload < 10 METs and an abnormal MPI scan were independent predictors of hard events. CONCLUSIONS: MPI is able to stratify patients with known CAD achieving ≥ 10 METs for the occurrence of all-cause death and nonfatal MI, with incremental prognostic value over ECG stress test alone.

Prognostic value of a faster, low-radiation myocardial perfusion SPECT protocol in a CZT camera.

To determine the prognostic value of a new, ultrafast, low dose myocardial perfusion SPECT (MPS) protocol in a cadmium-zinc telluride (CZT) camera. CZT cameras have introduced significant progress in MPS imaging, offering high-quality images despite lower doses and scan time. Yet, it is unknown if, with such protocol changes, the prognostic value of MPS is preserved. Patients had a 1-day 99 m-Tc-sestamibi protocol, starting with the rest (185-222 MBq) followed by stress (666-740 MBq). Acquisition times were 6 and 3 min, respectively. MPS were classified as normal or abnormal perfusion scans and summed scores of stress, rest, and difference (SSS, SRS and SDS), calculated. Patients were followed with 6-month phone calls. Hard events were defined as death or nonfatal myocardial infarction. Late revascularization was that occurring after 60 days of MPS. 2930 patients (age 64.0 ± 12.1 years, 53.3% male) were followed for 30.7 ± 7.5 months. Mean dosimetry was 6 mSv and mean total study time, 48 ± 13 min. The annual hard event and late revascularization rate were higher in patients with greater extension of defect and ischemia. SSS was higher in patients with hard events compared to those without events (2.6 ± 4.9 vs. 5.0 ± 6.3, p < 0.001), as well as the SDS (0.7 ± 1.9 vs. 1.7 ± 3.4, p < 0.00). The same was true for patients with or without late revascularization (SSS: 2.5 ± 4.7 vs. 6.6 ± 7.1; SDS: 0.6 ± 1.7 vs. 2.9 ± 3.8, p < 0.01). A new, faster, low-radiation, MPS protocol in a CZT camera maintain the ability to stratify patients with increased risk of events, showing that, in the presence of greater extension of defect or ischemia, patients presented higher rates of hard events and late revascularization.

"Metabolically healthy" obesity: Prevalence, clinical features and association with myocardial ischaemia.

OBJECTIVE: To evaluate the prevalence of the "metabolically healthy" (MH) or "metabolically unhealthy" (MU) obesity phenotypes and their association with cardiorespiratory fitness and inducible myocardial ischaemia. METHODS: Individuals without known coronary artery disease undergoing myocardial perfusion single-photon emission computed tomography (MPS) were studied. Those without dyslipidemia, hypertension, or diabetes were considered MH, and when ≥1 of these was present, MU status was considered present. Summed stress and difference perfusion scores (SSS and SDS, respectively) were calculated; a SDS >1 defined ischaemic MPS. RESULTS: MH patients were 35.0% of the nonobese population and 23.5% of the obese (p<0.001). The prevalence of ischaemia was not significantly different between MH patients with obesity or MH patients without obesity (10.9% vs 9.1%, p=0.3), except for patients with body mass index ≥40kg/m2 (21.9%). MH obese patients were less frequently able to exercise and had lower exercise capacity than the nonobese patients. CONCLUSIONS: The prevalence of myocardial ischaemia was not significantly different between MH obese or nonobese individuals, supporting the concept of the "metabolically healthy obesity". However, there are other factors involved, such as the ability to exercise, that influence the risk of myocardial ischaemia, limiting the "safety" of that obesity phenotype.

Comparison of myocardial T1 and T2 values in 3 T with T2* in 1.5 T in patients with iron overload and controls.

Myocardial iron quantification remains limited to 1.5 T systems with T2* measurement. The present study aimed at comparing myocardial T2* values at 1.5 T to T1 and T2 mapping at 3.0 T in patients with iron overload and healthy controls. A total of 17 normal volunteers and seven patients with a history of myocardial iron overload were prospectively enrolled. Mid-interventricular septum T2*, native T1 and T2 times were quantified on the same day, using a multi-echo gradient-echo sequence at 1.5 T and T1 and T2 mapping sequences at 3.0 T, respectively. Subjects with myocardial iron overload (T2* < 20 ms) in comparison with those without had significantly lower mean myocardial T1 times (868.9 ± 120.2 vs. 1170.3 ± 25.0 ms P = 0.005 respectively) and T2 times (34.9 ± 4.7 vs. 45.1 ± 2.0 ms P = 0.007 respectively). 3 T T1 and T2 times strongly correlated with 1.5 T, T2* times (Pearson's r = 0.95 and 0.91 respectively). T1 and T2 measures presented less variability than T2* in inter- and intra-observer analysis. Native myocardial T1 and T2 times at 3 T correlate closely with T2* times at 1.5 T and may be useful for myocardial iron overload quantification.

Prognostic evaluation in obese patients using a dedicated multipinhole cadmium-zinc telluride SPECT camera.

The purpose of this study is to evaluate the prognostic value of myocardial perfusion SPECT obtained in CZT cameras (CZT-SPECT) with multipinhole collimation in obese patients. CZT-SPECT may be technically challenging in the obese, and its prognostic value remains largely unknown. Patients underwent single-day, rest/stress (supine and prone) imaging. Images were visually inspected and graded as poor, fair or good/excellent. Summed stress and difference scores (SSS and SDS, respectively) were converted into percentages of total perfusion defect and of ischemic defect by division by the maximum possible score. Obesity was defined as a body mass index (BMI) ≥ 30 kg/m(2) and classified as class I (BMI 30-34.9 kg/m(2)), II (BMI 35-39.9 kg/m(2)), or III (BMI ≥ 40 kg/m(2)). Patients were followed-up by telephone interview for the occurrence of all-cause death, myocardial infarction or revascularization. A Cox proportional hazards analysis was used to assess the independent predictors of death. Among 1396 patients, 365 (26.1 %) were obese (mean BMI 33.9 ± 3.6; 17.5 % class I, 3.4 % class II, and 3.4 % class III). Image quality was good/excellent in 94.5 % of the obese patients. The annualized mortality rates were not significantly different among obese and non-obese patients, being <1 % with normal CZT-SPECT, and increased with the degree of scan abnormality in both obese and non-obese patients. Age, the use of pharmacologic stress and an abnormal CZT-SPECT, but not obesity, were independent predictors of death. In obese patients, single-day rest/stress CZT-SPECT with a multipinhole camera provides prognostic discrimination with high image quality.

Influence of typical angina versus inducible myocardial ischemia in the contemporary management of stable coronary artery disease.

OBJECTIVE: To investigate, in patients with known or suspected coronary artery disease (CAD) undergoing myocardial perfusion single-photon emission computed tomography (MPS),the interaction between patient symptoms and single-photon emission computed tomography (SPECT) results, and their effects on patient outcomes. Previous data have shown that medical treatment may be as beneficial as invasive treatment for most patients with stable CAD. Nonetheless, patient presentation with typical angina (TA) seems to still lead to more aggressive management, regardless of the amount of myocardial ischemia detected by noninvasive methods. METHODS: Over 33 ± 20 months, 2958 patients undergoing stress/rest cardiac SPECT were followed. Summed stress, rest and difference scores (SSS, SRS and SDS, respectively) were analyzed. Abnormal SPECT was defined as a SSS>3, and ischemic SPECT as a SDS>1. During follow up, cardiac catheterization (CATH), myocardial revascularization (either percutaneous or surgical), myocardial infarction (MI) and all-cause death were evaluated. RESULTS: TA was found in 228 patients (7.7%). Comparing patients with TA with those without it, the former more often had had abnormal (43.0% versus 34.3%, p < 0.001) and ischemic SPECT (25.9% versus 13.6%, p < 0.001). Also, higher rates of MI (2.0% versus 0.6%, p < 0.001), CATH (10.1% versus 4.7%, p < 0.001) and revascularization (7.8% versus 3.0%, p < 0.001) were observed, while death was not significantly different (1.5% versus 1.0%, p = 0.2). Even in the absence of ischemia in SPECT, patients with TA had higher CATH and revascularization rates; death, again, was not significantly increased. CONCLUSION: Although patients with TA more often had ischemic SPECT, all-cause death was not significantly increased. Nonetheless, TA was associated with more frequent referrals for CATH and revascularization, even with nonischemic SPECT. This may suggest that despite current evidence, the management of stable patients with known or suspected CAD is influenced by symptom type.

Is chronotropic incompetence a limitation in the evaluation of myocardial ischemia and prognosis?

OBJECTIVE: The aim of this study was to evaluate whether chronotropic incompetence (CI), the inability to reach 85% of the maximal predicted heart rate during exercise, affects the assessment of myocardial ischemia and prognosis in patients undergoing myocardial perfusion single-photon emission computed tomography (MPS). METHODS: Patients undergoing exercise/rest MPS were studied. Those taking drugs with negative chronotropic properties were excluded. Summed stress, rest, and difference scores (SSS, SRS, and SDS, representing, respectively, the extent and severity of the total perfusion defect, fibrosis, or ischemia) were calculated. Patients were followed up for the occurrence of hard events (death or myocardial infarction) or myocardial revascularization for 36±20 months. RESULTS: A total of 391 patients were studied; among them, 11.5% had CI. All perfusion scores were higher in patients with CI. On logistic regression, history of myocardial infarction and SDS were found to be independent predictors of CI. On comparing patients with and without CI, the former more often had hard events (12.5 vs. 0.9%, P=0.007) and revascularization (20.0 vs. 8.1%, P=0.003). CONCLUSION: CI was associated with myocardial ischemia. Higher rates of hard events and revascularization were observed in patients with CI, in accordance with the larger extent of myocardial ischemia found in these patients. Performing MPS in the setting of CI may maintain the diagnostic and prognostic abilities of the test.

Biodistribution of bone marrow mononuclear cells in chronic chagasic cardiomyopathy after intracoronary injection.

BACKGROUND: Animal and human clinical studies have indicated that bone marrow (BM) mononuclear cell (MNC) therapy for Chagasic Cardiomyopathy (ChC) is feasible, safe and potentially efficacious. Nevertheless, little is known about the retention of these cells after intracoronary (IC) infusion. METHODS: Our study investigated the homing of technetium-99m ((99m)Tc) labeled BM MNCs and compared it to thallium-201 ((201)Tl) myocardial perfusion images using the standard 17-segment model. Six patients with congestive heart failure of chagasic etiology were included. RESULTS: Scintigraphic images revealed an uptake of 5.4%±1.7, 4.3%±1.5 and 2.3%±0.6 of the total infused radioactivity in the heart after 1, 3 and 24h, respectively. The remaining activity was distributed mainly to the liver and spleen. Of 102 segments analyzed, homing took place in 36%. Segments with perfusion had greater homing (58.6%) than those with decreased or no perfusion (6.8%), p<0.0001. There was no correlation between the number of injected cells and the number of segments with homing for each patient (r=-0.172, p=0.774). CONCLUSIONS: These results indicate that (99m)Tc-BM MNCs delivered by IC injection homed to the chagasic myocardium. However, cell biodistribution was heterogeneous and limited, being strongly associated with the myocardial perfusion pattern at rest. These initial data suggest that the IC route may present limitations in chagasic patients and that alternative routes of cell administration may be necessary.

Comparison between short-acquisition myocardial perfusion SPECT reconstructed with a new algorithm and conventional acquisition with filtered backprojection processing.

OBJECTIVE: To compare a novel reconstruction package (Evolution for Cardiac), used to improve image quality in myocardial perfusion single photon emission computed tomography (MPS) and enable shorter scan acquisitions, to filtered backprojection used for conventional time acquisitions. METHODS: Forty-four patients who underwent 2-day Tc-99m sestamibi MPS had both standard [SD: 14-min scan and filtered backprojection processing] and short (SH: 6-min scan and iterative reconstruction with Evolution for Cardiac) studies. In a 17-segment model of the left ventricle, each segment was automatically scored 0-4 (normal to absent radiotracer activity); summed stress, rest and difference scores (SSS, SRS, SDS) were obtained. Spearman's test assessed the correlation between scores from SD and SH studies, and Bland-Altman plots evaluated absolute and mean differences of scores between these studies. RESULTS: The SSS, SRS, and SDS were not statistically different between SD and SH studies (SSS: 5.9 + or - 6.6 vs. 5.8 + or - 6.5; SRS: 2.6 + or - 3.5 vs. 2.6 + or - 2.9; SDS: 3.3 + or - 5.8 vs. 3.2 + or - 5.7). Significant correlations were observed between SD and SH studies regarding SSS (R(2)=0.93), SRS (R(2)=0.85), and SDS (R(2)=0.9) (all P<0.001). Bland-Altman plots showed that differences in SSS, SRS, and SDS fell within 2 standard deviations of the average differences between SD and SH studies. Overall agreement between clinical readings of SD and SH scans was good (up to 100% in abnormal scans). CONCLUSION: A new reconstruction package (Evolution for Cardiac) enabled short MPS acquisition without changes in quantitative perfusion results when compared with conventional acquisition and processing.

Reduced heart rate response to dipyridamole as a marker of left ventricular dysfunction in diabetic patients undergoing myocardial perfusion scintigraphy.

PURPOSE OF THE REPORT: This study sought to find among clinical, hemodynamic and left ventricular perfusion and function data obtained from myocardial perfusion scintigraphy (MPS), those associated with a reduced heart rate (HR) response to dipyridamole in diabetic patients. This phenomenon, although previously described as a marker of autonomic dysfunction in patients with diabetes, has not been fully elucidated. MATERIALS AND METHODS: One hundred two consecutive diabetic patients undergoing dual-isotope (rest Tl-201/dipyridamole stress Tc-99m tetrofosmin) MPS were prospectively enrolled. A reduced HR response to dipyridamole was considered present if the ratio between maximal HR after dipyridamole infusion and rest HR was

Influence of chronic renal failure on the heart rate response to dipyridamole in patients undergoing myocardial perfusion SPECT.

BACKGROUND: Dipyridamole promotes a reduction in blood pressure and an increase in heart rate (HR), considered the normal hemodynamic response to the drug. Data suggest that patients with chronic renal failure (CRF) have an attenuation of this hemodynamic response. This study sought to evaluate the HR response to dipyridamole and its determinants in patients with or without CRF undergoing gated myocardial perfusion single photon emission computed tomography. METHODS AND RESULTS: Consecutive patients (n = 355, 9.6% with CRF) undergoing rest/dipyridamole myocardial perfusion single photon emission computed tomography were evaluated. The HR response to dipyridamole was considered to be reduced if the HR ratio (maximal HR/rest HR) was 1.20 or less. A logistic regression analysis determined independent predictors of a blunted HR response. A reduced HR response was found in 84.4% of patients with CRF and 40.6% of those without CRF (P < .0001). In patients without CRF the independent predictors of abnormal HR response were hypertension, rest and differential perfusion scores, and left ventricular ejection fraction. In contrast, in CRF patients there was no significant association of any of the studied variables with abnormal HR response. CONCLUSIONS: An abnormal HR response to dipyridamole is frequently found in patients with CRF. Different mechanisms may account for abnormal HR response in patients with or without CRF.

Relation between postexercise abnormal heart rate recovery and myocardial damage evidenced by gated single-photon emission computed tomography.

Abnormal heart rate recovery (HRR) after exercise has been associated with increased cardiac mortality. The ability of gated myocardial perfusion single-photon emission computed tomography (SPECT) to evaluate myocardial perfusion and function simultaneously might make it helpful in determining possible mechanisms that are involved in this finding. This study investigated the association between abnormal HRR and other indicators of risk for cardiovascular events. Patients (n = 1,296, 784 men; 57 +/- 11 years of age) who underwent exercise/technetium-99m sestamibi gated myocardial perfusion SPECT at rest were prospectively enrolled. Exercise treadmill testing was performed according to a symptom-limited Bruce's protocol. HRR was obtained from the subtraction of heart rate in the first minute of recovery after exercise treadmill testing from maximal heart rate during exercise. Myocardial perfusion SPECT was semi-quantitatively analyzed using a 17-segment left ventricular model. Left ventricular ejection fraction was automatically calculated using quantitative gated SPECT software. In our study, patients with abnormal HRR were older, more frequently diabetic, and hypertensive and had previous myocardial infarction and myocardial revascularization, higher heart rate at rest and perfusion defect quantification scores, lower left ventricular ejection fraction, and larger left ventricular volumes than did patients with normal HRR. In multivariable analysis, age (p <0.0001), heart rate at rest (p <0.0001), left ventricular ejection fraction (p <0.0001), and perfusion defect extent and severity at rest (p = 0.038) were independent predictors of abnormal HRR. In conclusion, abnormal HRR was significantly associated with lower left ventricular ejection fraction and with perfusion defect extent and severity at rest, but not with gated SPECT markers of myocardial ischemia. Therefore, abnormal HRR may reflect myocardial damage.

Incremental prognostic value of myocardial perfusion 99m-technetium-sestamibi SPECT in the elderly.

Coronary artery disease (CAD) is the main cause of death in elderly patients. Single-photon emission computed tomography (SPECT) with technetium-99m ((99m)Tc)-labeled agents is extremely useful for the diagnosis and risk stratification of CAD in the general population. However, its prognostic value for the elderly has not been established. This study examined disease outcome in 328 patients aged 74 or older, with suspected CAD who were submitted to either pharmacological (dipyridamole) or exercise stress SPECT with (99m)Tc-sestamibi, seven of whom were completely lost to follow-up. Endpoints were defined as hard (myocardial infarction or cardiac death) or total events (myocardial infarction, cardiac death or myocardial revascularization). Mean follow-up was 34+/-15 months. During this period 24 cardiac deaths, 11 myocardial infarctions and 21 cases of revascularization were observed. Perfusion defects were found in 27.1% of patients (12.8% reversible, 6.2% partially reversible and 8.1% fixed). Abnormal studies were predominant in men, patients with chest pain and those with ST-T abnormalities in the baseline electrocardiogram (ECG) or in the exercise treadmill test. An abnormal scan was significantly associated with cardiac events (P<0.0001). Multivariate analysis revealed that a abnormal scan was the most important independent predictor of hard or total cardiac events. Event rates increased according to myocardial perfusion scintigraphy (MPS): <1.0% of hard events per year in patients with normal MPS versus 14.3% per year in those with abnormal MPS. (99m)Tc-sestamibi SPECT was demonstrated to be a powerful tool for the prognostic evaluation of elderly patients with suspected CAD.

Incremental value of combined perfusion and function over perfusion alone by gated SPECT myocardial perfusion imaging for detection of severe three-vessel coronary artery disease.

OBJECTIVES: We hypothesized that combining functional assessment to perfusion enhances the ability of electrocardiographic gating Tc-99m sestamibi single photon emission computed tomography (gated SPECT) myocardial perfusion imaging (MPI) to detect defects in multiple vascular territories in patients with severe three-vessel coronary artery disease (3VD). BACKGROUND: In patients with 3VD, perfusion defects in multiple vascular territories may not always be evident due to globally reduced perfusion. METHODS: Gated SPECT MPIs were interpreted sequentially with perfusion first, followed by combined perfusion/function, in 143 patients with angiographic 3VD and a control group of 112 non-3VD patients. All patients underwent coronary arteriography within one month of MPI. RESULTS: In 3VD patients, combined perfusion/function analysis yielded significantly greater numbers of abnormal segments/patient (6.2 +/- 4.7 vs. 4.1 +/- 2.8, p < 0.001) and more defects in multiple vascular territories (60% vs. 46%, p < 0.05) than perfusion alone. In the control group, there were no differences between the combined perfusion/function and perfusion alone interpretations. Multivariate analysis of 15 different clinical, stress, and scintigraphic variables in all patients revealed age (p < 0.0001) and number of abnormal vascular territories by combined perfusion/function (p < 0.0001) to be the most powerful predictors of 3VD. Addition of functional data to clinical, stress, and perfusion yielded a significant increase in the predictive value of 3VD (global chi-square: 131.7 vs. 89.8, p < 0.00001). Specificity of combined perfusion/function analysis was not lower than perfusion alone (72% vs. 69%, p = NS). CONCLUSIONS; Adjunctive assessment of function with perfusion by gated SPECT MPI enhances the detection of defects in multiple vascular territories in patients with severe 3VD, without adversely affecting its specificity.

Prevalence and prognostic value of perfusion defects detected by stress technetium-99m sestamibi myocardial perfusion single-photon emission computed tomography in asymptomatic patients with diabetes mellitus and no known coronary artery disease.

Coronary artery disease (CAD) is the leading cause of morbidity and mortality in diabetics. Early diagnosis of CAD and identification of high-risk subgroups, followed by appropriate therapy, may therefore enhance survival. This study sought to determine the value of stress myocardial perfusion single-photon emission computed tomography (SPECT) with technetium-99m sestamibi to detect perfusion defects and predict cardiac events in asymptomatic diabetics. One hundred eighty asymptomatic diabetics without known CAD who underwent 2-day stress technetium-99m sestamibi SPECT were followed up for 36 +/- 18 months. End points were defined as hard (myocardial infarction or cardiac death) or total events (myocardial infarction, cardiac death, or late revascularization). Logistic regression analysis evaluated clinical variables, type of stress, exercise treadmill test (ETT), and SPECT as predictors of end points. Perfusion defects were found in 26% of patients (15% reversible, 6% mixed, and 5% fixed). Clinical or ETT variables were not associated with perfusion defect type or with hard events. However, male gender predicted total events (chi-square 3.3; p = 0.01). An abnormal SPECT significantly increased the risk of hard events (chi-square 5.4; p = 0.001) and total events (chi-square 7.4; p = 0.0001). Extensive defects determined the highest risk of total events (chi-square 18.8; p = 0.0001). Event rates increased according to SPECT: 2% of hard events per year and 5% of total events per year in patients with normal SPECT versus 9% per year and 38% per year, respectively, in those with abnormal SPECT. Importantly, a normal SPECT identified a relatively low-risk subgroup of patients. Thus, stress technetium-99m sestamibi SPECT was useful in evaluating asymptomatic diabetics for the presence of CAD, and effectively risk-stratified this population.