A combined static-dynamic single-dose imaging protocol to compare quantitative dynamic SPECT with static conventional SPECT.

BACKGROUND: SPECT myocardial perfusion imaging (MPI) is a clinical mainstay that is typically performed with static imaging protocols and visually or semi-quantitatively assessed for perfusion defects based upon the relative intensity of myocardial regions. Dynamic cardiac SPECT presents a new imaging technique based on time-varying information of radiotracer distribution, which permits the evaluation of regional myocardial blood flow (MBF) and coronary flow reserve (CFR). In this work, a preliminary feasibility study was conducted in a small patient sample designed to implement a unique combined static-dynamic single-dose one-day visit imaging protocol to compare quantitative dynamic SPECT with static conventional SPECT for improving the diagnosis of coronary artery disease (CAD). METHODS: Fifteen patients (11 males, four females, mean age 71 ± 9 years) were enrolled for a combined dynamic and static SPECT (Infinia Hawkeye 4, GE Healthcare) imaging protocol with a single dose of 99mTc-tetrofosmin administered at rest and a single dose administered at stress in a one-day visit. Out of 15 patients, eleven had selective coronary angiography (SCA), 8 within 6 months and the rest within 24 months of SPECT imaging, without intervening symptoms or interventions. The extent and severity of perfusion defects in each myocardial region was graded visually. Dynamically acquired data were also used to estimate the MBF and CFR. Both visually graded images and estimated CFR were tested against SCA as a reference to evaluate the validity of the methods. RESULTS: Overall, conventional static SPECT was normal in ten patients and abnormal in five patients, dynamic SPECT was normal in 12 patients and abnormal in three patients, and CFR from dynamic SPECT was normal in nine patients and abnormal in six patients. Among those 11 patients with SCA, conventional SPECT was normal in 5, 3 with documented CAD on SCA with an overall accuracy of 64%, sensitivity of 40% and specificity of 83%. Dynamic SPECT image analysis also produced a similar accuracy, sensitivity, and specificity. CFR was normal in 6, each with CAD on SCA with an overall accuracy of 91%, sensitivity of 80%, and specificity of 100%. The mean CFR was significantly lower for SCA detected abnormal than for normal patients (3.86±1.06 vs 1.94±0. 0.67, P < 0.001). CONCLUSIONS: The visually assessed image findings in static and dynamic SPECT are subjective, and may not reflect direct physiologic measures of coronary lesion based on SCA. The CFR measured with dynamic SPECT is fully objective, with better sensitivity and specificity, available only with the data generated from the dynamic SPECT method.

Noninvasive PET quantitative myocardial blood flow with regadenoson for assessing cardiac allograft vasculopathy in orthotopic heart transplantation patients.

BACKGROUND: Risk stratification and early detection of cardiac allograft vasculopathy (CAV) is essential in orthotopic heart transplantation (OHT) patients. This study assesses the changes in myocardial blood flow (MBF) noninvasively in OHT patients using quantitative cardiac PET with regadenoson. METHODS: Twelve patients (Group 1) (8 males, 4 females, mean age 55 ± 7 years) with no history of post OHT myocardial ischemia were enrolled 5.4 ± 2.0 years after OHT. Fifteen patients (Group 2) (9 males, 6 females, mean age 71 ± 9 years) with intermediate pretest probability but not documented evidence for coronary artery disease (CAD) were also included to serve as control. Global and regional MBFs were assessed using dynamic 13N-NH3 PET at rest and during regadenoson-induced hyperemia. The coronary flow reserve (CFR) was also calculated as the ratio of hyperemic to resting MBF. RESULTS: Mean regadenoson-induced rate-pressure products were similar in both groups, while there was an increase in resting rate-pressure product in Group 1 patients. Both mean and median values of resting MBF were higher in Group 1 than Group 2 patients (1.33 ± 0.31 and 1.01 ± 0.21 mL/min/g for Groups 1 and 2, respectively, P < .001), while mean hyperemic MBF values were similar in both Groups (2.68 ± 0.84 and 2.64 ± 0.94 mL/min/g, P = NS) but median hyperemic MBF values were lower in Group 1 than Group 2 patients (2.0 vs. 2.60 mL/min/g, P = .018). Both mean and median CFR values demonstrated a significant reduction for Group 1 compared to Group 2 patients (2.07 ± 0.74 vs 2.63 ± 0.48, P = .025). CONCLUSIONS: This study suggests that the MBF in OHT patients may be abnormal at resting state with diminished CFR. This hints that the epicardial and microvascular coronary subsystem may be exacerbated after OHT leading to the gradual progression of CAV.

Measurement of absolute myocardial blood flow in humans using dynamic cardiac SPECT and 99mTc-tetrofosmin: Method and validation.

BACKGROUND: The objective of this study was to measure myocardial blood flow (MBF) in humans using 99mTc-tetrofosmin and dynamic single-photon emission computed tomography (SPECT). METHODS: Dynamic SPECT using 99mTc-tetrofosmin and dynamic positron emission tomography (PET) was performed on a group of 16 patients. The SPECT data were reconstructed using a 4D-spatiotemporal iterative reconstruction method. The data corresponding to 9 patients were used to determine the flow-extraction curve for 99mTc-tefrofosmin while data from the remaining 7 patients were used for method validation. The nonlinear tracer correction parameters A and B for 99mTc-tefrofosmin were estimated for the 9 patients by fitting the flow-extraction curve [Formula: see text] for K 1 values estimated with 99mTc-tefrofosmin using SPECT and MBF values estimated with 13N-NH3 using PET. These parameters were then used to calculate MBF and coronary flow reserve (CFR) in three coronary territories (LAD, RCA, and LCX) using SPECT for an independent cohort of 7 patients. The results were then compared with that estimated with 13N-NH3 PET. The flow-dependent permeability surface-area product (PS) for 99mTc-tefrofosmin was also estimated. RESULTS: The estimated flow-extraction parameters for 99mTc-tefrofosmin were found to be A = 0.91 ± 0.11, B = 0.34 ± 0.20 (R 2 = 0.49). The range of MBF in LAD, RCA, and LCX was 0.44-3.81 mL/min/g. The MBF between PET and SPECT in the group of independent cohort of 7 patients showed statistically significant correlation, r = 0.71 (P < .001). However, the corresponding CFR correlation was moderate r = 0.39 yet statistically significant (P = .037). The PS for 99mTc-tefrofosmin was (0.019 ± 0.10)*MBF + (0.32 ± 0.16). CONCLUSIONS: Dynamic cardiac SPECT using 99mTc-tetrofosmin and a clinical two-headed SPECT/CT scanner can be a useful tool for estimation of MBF.

Assessment of late-term progression of cardiac allograft vasculopathy in patients with orthotopic heart transplantation using quantitative cardiac 82Rb PET.

The risk stratification and long-term survival of patients with orthotopic heart transplantation (OHT) is impacted by the complication of cardiac allograft vasculopathy (CAV). This study evaluates changes in myocardial blood flow (MBF) and myocardial coronary flow reserve (CFR) in a group of long-term OHT patients using quantitative cardiac 82Rb-positron emission tomography (PET). Twenty patients (7 females and 13 males, mean age = 72.7 ± 12.2 years with CAV and 62.9 ± 7.2 years without CAV and post-OHT mean time = 13.9 years), were evaluated retrospectively using dynamic cardiac 82Rb-PET at rest and regadenoson-induced stress. The patients also underwent selective coronary angiography (SCA) for diagnosis and risk stratification. CAV was diagnosed based on SCA findings and maximal intimal thickness greater than 0.5 mm, as defined by International Society of Heart and Lung Transplantation (ISHLT). Global and regional MBFs were estimated in three vascular territories using the standard 1-tissue compartment model for dynamic 82Rb-PET. The myocardial CFR was also calculated as the ratio of peak stress MBF to rest MBF. Among twenty patients, seven had CAV in, at least, one major coronary artery (ISHLT CAV grade 1 or higher) while 13 patients did not have CAV (NonCAV). Mean rate-pressure products (RPP) at rest were significantly elevated in CAV patients compared to those without CAV (P = 0.002) but it was insignificant at stress (P = NS). There was no significant difference in the stress MBFs between CAV and NonCAV patients (P = NS). However, the difference in RPP-normalized stress MBFs was significant (P = 0.045), while RPP-normalized MBFs at rest was not significant (P = NS). Both CFR and RPP-normalized CFR were significantly lower in CAV compared to NonCAV patients (P < 0.001). There were significant correlations between MBFs and RPPs at rest for both CAV (ρ = 0.764, P = 0.047) and NonCAV patients (ρ = 0.641, P = 0.017), while there were no correlations at stress for CAV (ρ = 0.232, P = NS) and NonCAV patients (ρ = 0.068, P = NS). This study indicates that the resting MBF is higher in late-term post-OHT patients. The high resting MBF and reduced CFR suggest an unprecedented demand of blood flow and blunted response to stress due to impaired vasodilatory capacity that is exacerbated by the presence of CAV.

The metabolic syndrome, diabetes, and subclinical atherosclerosis assessed by coronary calcium.

OBJECTIVES: We compared the prevalence and extent of coronary artery calcium (CAC) among persons with the metabolic syndrome (MetS), diabetes, and neither condition. BACKGROUND: The prevalence and extent of CAC has not been compared among those with MetS, diabetes, or neither condition. METHODS: Of 1,823 persons (36% female) age 20 to 79 years who had screening for CAC by computed tomography, 279 had MetS, 150 had diabetes, and the remainder (n = 1,394) had neither condition. Metabolic syndrome was defined with >or=3 of the following: body mass index >or=30 kg/m(2); high-density lipoprotein cholesterol <40 mg/dl if male or <50 mg/dl if female; triglycerides >or=150 mg/dl; blood pressure >or=130/85 mm Hg or on treatment; or fasting glucose 110 to 125 mg/dl. The prevalence and odds of any and significant (>or=75th percentile) CAC among these groups and by number of MetS risk factors were determined. RESULTS: Those with neither MetS nor diabetes, MetS, or diabetes had a prevalence of CAC of 53.5%, 58.8%, and 75.3% (p < 0.001), respectively, among men and 37.6%, 50.8%, and 52.6% (p < 0.001), respectively, among women. Coronary artery calcium increased by the number (0 to 5) of MetS risk factors (from 34.0% to 58.3%) (p < 0.001). Forty-one percent of subjects with MetS had either a >20% 10-year risk of CHD or CAC >or=75th percentile for age and gender. Risk factor-adjusted odds for the presence of CAC were 1.40 (95% confidence interval [CI] 1.05 to 1.87) among those with MetS and 1.67 (95% CI 1.12 to 2.50) among those with diabetes, versus those with neither condition. CONCLUSIONS: Those with MetS or diabetes have an increased likelihood of CAC compared with those having neither condition.

Influence of angiographic collateral circulation on myocardial perfusion in patients with chronic total occlusion of a single coronary artery and no prior myocardial infarction.

UNLABELLED: The functional role of various angiographic grades for coronary collaterals remains controversial. The aim of this study was to assess the influence of the Rentrop angiographic grading of coronary collaterals on myocardial perfusion in patients with single-vessel chronic total occlusion (CTO) and no prior myocardial infarction (MI). METHODS: The study included 56 patients with single-vessel CTO and no prior MI who underwent rest-stress myocardial perfusion SPECT and coronary angiography within 6 mo. All patients had angiographic evidence of coronary collaterals. Patients were divided according to the Rentrop classification: Group I had grade 1 or 2 (n = 25) and group II had grade 3 collaterals (n = 31). RESULTS: Group I had a higher frequency of resting regional wall motion abnormalities on left ventriculography (52.6% vs. 19.2% [P = 0.019]). The mean perfusion scores of the overall population showed severe and extensive stress perfusion defects (summed stress score of 14.1 +/- 7.1 and summed difference score of 12.9 +/- 6.9) but minimal resting perfusion defects (summed rest score of 1.0 +/- 2.7). No perfusion scores differed between the 2 groups. The perfusion findings suggested that chronic stunning rather than hibernation is the principal cause of regional wall motion abnormalities in these patients. CONCLUSION: In the setting of single-vessel CTO and no prior MI, coronary collaterals appear to protect against resting perfusion defects. Excellent angiographic collaterals may prevent resting regional wall motion abnormalities but do not appear to protect against stress-induced perfusion defects.

Relation of thoracic aortic and aortic valve calcium to coronary artery calcium and risk assessment.

Aortic calcium, aortic valve calcium (AVC), and coronary artery calcium (CAC) have been associated with cardiovascular event risk. We examined the prevalence of thoracic aortic calcium (TAC) and AVC in relation to the presence and extent of CAC, cardiovascular risk factors, and estimated risk of coronary heart disease (CHD). In 2,740 persons without known CHD aged 20 to 79 years, CAC was assessed by electron beam- or multidetector-computed tomography. We determined the prevalence of TAC and AVC in relation to CAC, CHD risk factors, and predicted 10-year risk of CHD. A close correspondence of TAC and AVC was observed with CAC. TAC and AVC increased with age; by the eighth decade of life, the prevalence of TAC was similar to that of CAC (>80%), and 36% of men and 24% of women had AVC. Age, male gender, and low-density lipoprotein cholesterol were directly related to the likelihood of CAC, TAC, and AVC; higher diastolic blood pressure and cigarette smoking additionally predicted CAC. Body mass index and higher systolic and lower diastolic blood pressures were also related to TAC, and higher body mass index and lower diastolic blood pressure were related to AVC. Calculated risk of CHD increased with the presence of AVC and TAC across levels of CAC. TAC and AVC provided incremental value over CAC in association with the 10-year calculated risk of CHD. If longitudinal studies show an incremental value of aortic and aortic valve calcium over that of CAC for prediction of cardiovascular events, future guidelines for risk assessment incorporating CAC assessment may additionally incorporate the measurement of aortic and/or aortic valve calcium.

Prognostic value of myocardial perfusion SPECT versus exercise electrocardiography in patients with ST-segment depression on resting electrocardiography.

BACKGROUND: The value of exercise-induced ST-segment depression for the prognostic evaluation of patients with 1 mm of ST depression or greater on the resting electrocardiogram is controversial. METHODS AND RESULTS: Patients who underwent exercise myocardial perfusion single photon emission computed tomography (MPS) and had resting ST depression of 1 mm or greater with a nondiagnostic exercise electrocardiographic response (n = 1122) were followed up for 3.4 +/- 2.3 years. Those with paced rhythm, pre-excitation, left bundle branch block, or myocardial revascularization within the first 60 days after MPS were excluded. Additional exercise-induced ST-segment depression was considered significant if > or = 2 mm MPS was scored semiquantitatively by use of a 20-segment model of the left ventricle; the percentage of myocardium involved with stress defects (% myo) was derived by normalizing to the maximal possible score of 80. Hard events were defined as nonfatal myocardial infarction or cardiac death. A Cox analysis was used to determine independent predictors of hard events among clinical, exercise, and nuclear variables. Hard event rates increased as a function of % myo for either patients with exercise-induced ST depression (1.4%/y for normal MPS vs 4.1%/y for % myo >10%, P < .03) or those without it (0.7%/y for normal MPS vs 3.0%/y for % myo >10%, P = .0001). Age, diabetes mellitus, shortness of breath as the presenting symptom, and % myo were independent predictors of hard events. Exercise-induced ST depression was predictive of hard events only when it was 3 mm or greater. The presence and extent of perfusion defects, reflected in the % myo, had incremental prognostic value over clinical variables and also over all degrees of exercise-induced ST depression. CONCLUSIONS: Although MPS effectively risk-stratifies patients with resting ST depression of 1 mm or greater, the prognostic value of exercise-induced ST depression is limited in these patients, with a small added risk when severe (> or = 3 mm).

Concordance of coronary artery calcium estimates between MDCT and electron beam tomography.

OBJECTIVE: The objective of our study was to compare MDCT with electron beam tomography (EBT) for the quantification of coronary artery calcification (CAC). MATERIALS AND METHODS: Sixty-eight patients underwent both MDCT and EBT within 2 months for the quantification of CAC. The images were scored in a blinded fashion and independently by two observers with a minimum of 7 days between the interpretations of images obtained from one scanner type to the other. RESULTS: Presence versus absence of CAC was discordant by EBT versus MDCT in 6% (n = 4) of the cases by observer 1, with one of these cases also discordant by observer 2. All cases except one (aortic calcium misidentified as CAC) were among those with a mean Agatston score of less than 5 present on EBT but absent on MDCT. EBT and MDCT scores correlated well (r = 0.98-0.99). The relative median variability between EBT and MDCT for the Agatston score was 24% for observer 1 and 27% for observer 2 and was 18% and 14%, respectively, for volume score (average for both observers: 27% for Agatston score and 16% for volume score). Scores were higher for EBT than MDCT in approximately half of the cases, with little systematic difference between the two (median EBT-MDCT difference: Agatston score, -0.55; volume score, 3.4 mm3). The absolute median difference averaged for the two observers was 28.75 for the Agatston score and 15.4 mm3 for the volume score. CONCLUSION: Differences in CAC measurements using EBT and MDCT are similar to interscan differences in CAC measurements previously reported for EBT or for other MDCT scanners individually.

An overview of contemporary nuclear cardiology.

Myocardial perfusion single photon emission computed tomography (SPECT) is a widely utilized noninvasive imaging modality for the diagnosis, prognosis, and risk stratification of coronary artery disease. It is clearly superior to the traditional planar technique in terms of imaging contrast and consequent diagnostic and prognostic yield. The strength of SPECT images is largely derived from the three-dimensional, volumetric nature of its image. Thus, this modality permits three-dimensional assessment and quantitation of the perfused myocardium and functional assessment through electrocardiographic gating of the perfusion images.

Use of atropine in patients with submaximal heart rate during exercise myocardial perfusion SPECT.

BACKGROUND: Failure to reach 85% of maximal predicted heart rate (MPHR) during exercise may render a myocardial perfusion single photon emission computed tomography (MPS) study nondiagnostic for ischemia detection. Although commonly used to increase heart rate (HR) during dobutamine stress, the administration of atropine for patients failing to achieve 85% of MPHR during exercise performed for MPS is still infrequent. METHODS AND RESULTS: Patients undergoing dual-isotope MPS were considered candidates for the study when, during exercise treadmill testing, they had less than 85% of MPHR and were unable to continue because of fatigue, without an ischemic response. Forty-seven patients (aged 65.3 +/- 12.5 years, 78.7% men) received atropine (0.6-1.2 mg). Maximal HR achieved before and after atropine was 118.0 +/- 14.8 beats/min (76.3% +/- 6.2% of MPHR) and 146.4 +/- 12.6 beats/min (94.4% +/- 8.1% of MPHR), respectively (P < .001). Of patients, 44 (93.6%) reached at least 85% of MPHR after atropine and had diagnostic MPS studies. After atropine, arrhythmias occurred in 14 patients (29.8%) and other minor side effects in 1 (2.1%). CONCLUSIONS: Atropine allows patients initially failing to achieve 85% of MPHR during exercise to increase HR and have a diagnostic MPS study, without major complications. It may provide an alternative to pharmacologic stress for patients with a blunted HR response to exercise.

Prognostic implications of atrial fibrillation in patients undergoing myocardial perfusion single-photon emission computed tomography.

OBJECTIVES: The aim of this research was to determine whether presence of atrial fibrillation (AF) provides incremental prognostic information relative to myocardial perfusion single-photon emission computed tomography (MPS) with respect to risk of cardiac death (CD). BACKGROUND: The prognostic significance of AF in patients undergoing MPS is not known. METHODS: A total of 16,048 consecutive patients undergoing MPS were followed-up for a mean of 2.21 +/- 1.15 years for the development of CD. Of those, 384 patients (2.4%) had AF. Cox proportional hazards method was used to compare clinical and perfusion data for the prediction of CD in patients with and without AF. RESULTS: Atrial fibrillation was a significant predictor of CD in patients with normal (1.6% per year vs. 0.4% per year in non-AF patients), mildly abnormal (6.3% per year vs. 1.2% per year), and severely abnormal MPS (6.4% per year vs. 3.7% per year) (p < 0.001 for all). By multivariable analysis, AF patients had worse survival (p = 0.001) even after adjustment for the variables most predictive of CD: age, diabetes, shortness of breath, use of vasodilator stress, rest heart rate, and the nuclear variables. In the 4,239 patients with left ventricular ejection fraction evaluated by gated MPS, AF demonstrated incremental prognostic value not only over clinical and nuclear variables, but also over left ventricular ejection in predicting CD (p = 0.014). CONCLUSIONS: The presence of AF independently increases the risk of cardiac events over perfusion and function variables in patients undergoing MPS. Patients with AF have a high risk of CD, even when MPS is only mildly abnormal. Whether patients with AF and mildly abnormal MPS constitute a group more deserving of early referral to cardiac catheterization is a question warranting further study.

Prognostic validation of a 17-segment score derived from a 20-segment score for myocardial perfusion SPECT interpretation.

BACKGROUND: Recently, a 17-segment model of the left ventricle has been recommended as an optimally weighted approach for interpreting myocardial perfusion single photon emission computed tomography (SPECT). Methods to convert databases from previous 20- to new 17-segment data and criteria for abnormality for the 17-segment scores are needed. METHODS AND RESULTS: Initially, for derivation of the conversion algorithm, 65 patients were studied (algorithm population) (pilot group, n = 28; validation group, n = 37). Three conversion algorithms were derived: algorithm 1, which used mid, distal, and apical scores; algorithm 2, which used distal and apical scores alone; and algorithm 3, which used maximal scores of the distal septal, lateral, and apical segments in the 20-segment model for 3 corresponding segments of the 17-segment model. The prognosis population comprised 16,020 consecutive patients (mean age, 65 +/- 12 years; 41% women) who had exercise or vasodilator stress technetium 99m sestamibi myocardial perfusion SPECT and were followed up for 2.1 +/- 0.8 years. In this population, 17-segment scores were derived from 20-segment scores by use of algorithm 2, which demonstrated the best agreement with expert 17-segment reading in the algorithm population. The prognostic value of the 20- and 17-segment scores was compared by converting the respective summed scores into percent myocardium abnormal. Conversion algorithm 2 was found to be highly concordant with expert visual analysis by the 17-segment model (r = 0.982; kappa = 0.866) in the algorithm population. In the prognosis population, 456 cardiac deaths occurred during follow-up. When the conversion algorithm was applied, extent and severity of perfusion defects were nearly identical by 20- and derived 17-segment scores. The receiver operating characteristic curve areas by 20- and 17-segment perfusion scores were identical for predicting cardiac death (both 0.77 +/- 0.02, P = not significant). The optimal prognostic cutoff value for either 20- or derived 17-segment models was confirmed to be 5% myocardium abnormal, corresponding to a summed stress score greater than 3. Of note, the 17-segment model demonstrated a trend toward fewer mildly abnormal scans and more normal and severely abnormal scans. CONCLUSION: An algorithm for conversion of 20-segment perfusion scores to 17-segment scores has been developed that is highly concordant with expert visual analysis by the 17-segment model and provides nearly identical prognostic information. This conversion model may provide a mechanism for comparison of studies analyzed by the 17-segment system with previous studies analyzed by the 20-segment approach.