82Rb Positron Emission Tomography Research Articles

Prognostic value of vasodilator response using rubidium-82 positron emission tomography myocardial perfusion imaging in patients with coronary artery disease.

Prognostic value of positron emission tomography (PET) myocardial perfusion imaging (MPI) is well established. There is paucity of data on how the prognostic value of PET relates to the hemodynamic response to vasodilator stress. We hypothesize that inadequate hemodynamic response will affect the prognostic value of PET MPI. Using a multicenter rubidium (Rb)-82 PET registry, 3406 patients who underwent a clinically indicated rest/stress PET MPI with a vasodilator agent were analyzed. Patients were categorized as, "responders" [increase in heart rate ≥ 10 beats per minute (bpm) and decrease in systolic blood pressure (SBP) ≥10mmHg], "partial responders" (either a change in HR or SBP), and "non-responders" (no change in HR or SBP). Primary outcome was all-cause death (ACD), and secondary outcome was cardiac death (CD). Ischemic burden was measured using summed stress score (SSS) and % left ventricular (LV) ischemia. After a median follow-up of 1.68years (interquartile range = 1.17- 2.55), there were 7.9% (n = 270) ACD and 2.6% (n = 54) CD. Responders with a normal PET MPI had an annualized event rate (AER) of 1.22% (SSS of 0-3) and 1.58% (% LV ischemia = 0). Partial and non-responders had higher AER with worsening levels of ischemic burden. In the presence of severe SSS ≥12 and LV ischemia of ≥10%, partial responders had an AER of 10.79% and 10.36%, compared to non-responders with an AER of 19.4% and 12.43%, respectively. Patient classification was improved when SSS was added to a model containing clinical variables (NRI: 42%, p < 0.001) and responder category was added (NRI: 61%, p < 0.001). The model including clinical variables, SSS and hemodynamic response has good discrimination ability (Harrell C statistics: 0.77 [0.74-0.80]). Hemodynamic response during a vasodilator Rb-82 PET MPI is predictive of ACD. Partial and non-responders may require additional risk stratification leading to altered patient management.

Independent prognostic value of left ventricular contractile reserve and chronotropic response in patients with reduced left ventricular ejection fraction undergoing vasodilator stress myocardial perfusion imaging with Rb-82 positron emission tomography.

We evaluated the prognostic value of heart rate reserve (ΔHR) and left ventricular ejection fraction reserve (ΔLVEF) among patients with systolic dysfunction. Inadequate ΔHR (maximal stress HR - resting HR) and ΔLVEF (LVEF at stress - LVEF at rest) in response to stress are associated with adverse cardiac events. However, the significance of an abnormal ΔHR and ΔLVEF in patients with systolic dysfunction has not been described. We performed a retrospective analysis of patients with rest LVEF < 45% who underwent dipyridamole stress-rest gated Rb-82 PET myocardial perfusion imaging (PET-MPI) at the Cleveland Clinic between 2006 and 2009. Stress LVEF and volumes were calculated using commercially available software (4DM). A Cox proportional hazards model (CPH) was used to examine the association between ΔLVEF, ΔHR, and all-cause death (ACD). Among 461 patients (mean age 65.7 ± 11.3 years, 82% men) 167 experienced ACD (median follow-up 1045 days). Survival was reduced among patients with ΔHR < 0 (1090 vs. 1300 days, P = 0.04) and ΔLVEF < 0 (1002 vs. 1057 days, P = 0.03). In a CPH after adjusting for confounding variables, ΔHR ≤ 0 and ΔLVEF ≤ 0 were associated with reduced survival (hazard ratio 0.93, P < 0.01 and 0.84, P = 0.01, respectively) with an interaction between age and ΔHR (χ2 = 8.1, P < 0.01). Our model predicts that the magnitude of ΔHR is associated with improved survival among younger patients. For any given ΔLVEF the magnitude of ΔHR has a greater positive effect on survival among younger patients. Both ΔHR and ΔLVEF during pharmacologic stress PET-MPI provide incremental value in predicting ACD among patients with systolic dysfunction.

Optimally Repeatable Kinetic Model Variant for Myocardial Blood Flow Measurements with 82Rb PET.

Purpose. Myocardial blood flow (MBF) quantification with 82Rb positron emission tomography (PET) is gaining clinical adoption, but improvements in precision are desired. This study aims to identify analysis variants producing the most repeatable MBF measures. Methods. 12 volunteers underwent same-day test-retest rest and dipyridamole stress imaging with dynamic 82Rb PET, from which MBF was quantified using 1-tissue-compartment kinetic model variants: (1) blood-pool versus uptake region sampled input function (Blood/Uptake-ROI), (2) dual spillover correction (SOC-On/Off), (3) right blood correction (RBC-On/Off), (4) arterial blood transit delay (Delay-On/Off), and (5) distribution volume (DV) constraint (Global/Regional-DV). Repeatability of MBF, stress/rest myocardial flow reserve (MFR), and stress/rest MBF difference (ΔMBF) was assessed using nonparametric reproducibility coefficients (RPCnp = 1.45 × interquartile range). Results. MBF using SOC-On, RVBC-Off, Blood-ROI, Global-DV, and Delay-Off was most repeatable for combined rest and stress: RPCnp = 0.21 mL/min/g (15.8%). Corresponding MFR and ΔMBF RPCnp were 0.42 (20.2%) and 0.24 mL/min/g (23.5%). MBF repeatability improved with SOC-On at stress (p < 0.001) and tended to improve with RBC-Off at both rest and stress (p < 0.08). DV and ROI did not significantly influence repeatability. The Delay-On model was overdetermined and did not reliably converge. Conclusion. MBF and MFR test-retest repeatability were the best with dual spillover correction, left atrium blood input function, and global DV.

Ranolazine and Microvascular Angina by PET in the Emergency Department: Results From a Pilot Randomized Controlled Trial

PurposeCoronary microvascular dysfunction (CMD) is a common but underdiagnosed cause of chest pain. Literature is scant regarding effective treatments. We explored the effect of ranolazine on coronary flow reserve (CFR) among symptomatic patients with CMD. MethodsThis pilot double-blinded randomized controlled trial included emergency department patients with chest pain and CMD admitted to an observation unit between June 2014 and November 2015. Participants were assessed by cardiac Rb-82 positron emission tomography and computed tomography imaging at baseline and 30 days. CMD was defined as CFR <2 corrected for rate pressure product or <2.5 uncorrected, with no evidence of obstructive or nonobstructive coronary artery disease or calcification. Patients with infarction, hypertensive urgency, heart failure, or prescribed QTc-prolonging drugs were excluded. Participants were assigned to ranolazine or placebo in a 2:1 ratio. Primary outcome was change in CFR at 30 days. FindingsWe enrolled 31 patients (71% female, mean [SD] age 50 [6] years) with CMD (mean [SD] corrected CFR 1.6 [0.3]). Ranolazine improved CFR at 30 days by 17% (P = 0.005) compared with 0% with placebo (P = 0.67). However, there was no significant difference in the primary outcome as measured by mean change in CFR (0.27 ranolazine compared with 0.06 placebo; 95% CI, −0.08 to 0.62). ImplicationsThe emergency department offers a unique venue to diagnose CMD with acute symptoms. In an exploratory randomized controlled trial of symptomatic patients with CMD and no coronary artery disease, promising results were seem with ranolazine and CFR improving at 30 days. Large robust clinical trials are needed to verify improvement of CMD in a sex-specific model. ClinicalTrials.gov identifier NCT02052011.

Reduced Myocardial Flow in Heart Failure Patients With Preserved Ejection Fraction.

There remains limited insight into the pathophysiology and therapeutic advances directed at improving prognosis for patients with heart failure with preserved ejection fraction (HFpEF). Recent studies have suggested a role for coronary microvascular dysfunction in HFpEF. Rb-82 cardiac positron emission tomography imaging is a noninvasive, quantitative approach to measuring myocardial flow reserve (MFR), a surrogate marker for coronary vascular health. The aim of this study was to determine whether abnormalities exist in MFR in patients with HFpEF without epicardial coronary artery disease. A total of 376 patients with ejection fraction ≥50%, no known history of obstructive coronary artery disease, and a confirmed diagnosis of heart failure (n=78) were compared with patients with no evidence of heart failure (n=298), further stratified into those with (n=186) and without (n=112) hypertension. Global and regional left ventricular MFR was calculated as stress/rest myocardial blood flow using Rb-82 positron emission tomography. Patients with HFpEF were more likely to be older, female, and have comorbid hypertension, diabetes mellitus, dyslipidemia, atrial fibrillation, anemia, and renal dysfunction. HFpEF was associated with a significant reduction in global MFR (2.16±0.69 in HFpEF versus 2.54±0.80 in hypertensive controls; P<0.02 and 2.89±0.70 in normotensive controls; P<0.001). A diagnosis of HFpEF was associated with 2.62 times greater unadjusted odds of having low global MFR (defined as <2.0) and remained a significant predictor of reduced global MFR after adjusting for comorbidities. HFpEF, in the absence of known history for obstructive epicardial coronary artery disease, is associated with reduced MFR independent of other risk factors.

Quantitative relationship between coronary artery calcium and myocardial blood flow by hybrid rubidium-82 PET/CT imaging in patients with suspected coronary artery disease

BackgroundWe assessed the relationship between coronary artery calcium (CAC) score, myocardial blood flow (MBF) and coronary flow reserve (CFR) in patients undergoing hybrid 82Rb positron emission tomography (PET)/computed tomography (CT) imaging for suspected CAD. We also evaluated if CAC score is able to predict a reduced CFR independently from conventional coronary risk factors. MethodsA total of 637 (mean age 58 ± 13 years) consecutive patients were studied. CAC score was measured according to the Agatston method and patients were categorized into 4 groups (0, 0.01-99.9, 100-399.9, and ≥400). Baseline and hyperemic MBF were automatically quantified. CFR was calculated as the ratio of hyperemic to baseline MBF and it was considered reduced when <2. ResultsGlobal CAC score showed a significant inverse correlation with hyperemic MBF and CFR (both P < .001), while no correlation between CAC score and baseline MBF was found. At multivariable logistic regression analysis age, diabetes and CAC score were independently associated with reduced CFR (all P < .001). The addition of CAC score to clinical data increased the global chi-square value for predicting reduced CFR from 81.01 to 91.13 (P < .01). Continuous net reclassification improvement, obtained by adding CAC score to clinical data, was 0.36. ConclusionsCAC score provides incremental information about coronary vascular function over established CAD risk factors in patients with suspected CAD and it might be helpful for identifying those with a reduced CFR.

Myocardial blood flow assessment with 82rubidium-PET imaging in patients with left bundle branch block

OBJECTIVES:Perfusion abnormalities are frequently seen in Single Photon Emission Computed Tomography (SPECT) when a left bundle branch block is present. A few studies have shown decreased coronary flow reserve in the left anterior descending territory, regardless of the presence of coronary artery disease.OBJECTIVE:We sought to investigate rubidium-82 (82Rb) positron emission tomography imaging in the assessment of myocardial blood flow and coronary flow reserve in patients with left bundle branch block.METHODS:Thirty-eight patients with left bundle branch block (GI), median age 63.5 years, 22 (58%) female, 12 with coronary artery disease (≥70%; GI-A) and 26 with no evidence of significant coronary artery disease (GI-B), underwent rest-dipyridamole stress 82Rb-positron emission tomography with absolute quantitative flow measurements using Cedars-Sinai software (mL/min/g). The relative myocardial perfusion and left ventricular ejection fraction were assessed in 17 segments. These parameters were compared with those obtained from 30 patients with normal 82Rb-positron emission tomography studies and without left bundle branch block (GII).RESULTS:Stress myocardial blood flow and coronary flow reserve were significantly lower in GI than in GII (p<0.05). The comparison of coronary flow reserve between GI-A and GI-B showed that it was different from the global coronary flow reserve (p<0.05) and the stress flow was significantly lower in the anterior than in the septal wall for both groups. Perfusion abnormalities were more prevalent in GI-A (p=0.06) and the left ventricular ejection fraction was not different between GI-A and GI-B, whereas it was lower in GI than in GII (p<0.001).CONCLUSION:The data confirm that patients with left bundle branch block had decreased myocardial blood flow and coronary flow reserve and coronary flow reserve assessed by 82Rb-positron emission tomography imaging may be useful in identifying coronary artery disease in patients with left bundle branch block.

CLINICAL PERFORMANCE OF RB82 MYOCARDIAL PERFUSION PET AND TC-99M SPECT IN PATIENTS WITH EXTREME OBESITY (BMI ≥ 40)

BACKGROUND: There has been a disproportionate increase in the rate of extreme obesity (EO), defined as BMI 40 kg/m, in North America in recent decades. The optimal myocardial perfusion imaging modality for the diagnosis of coronary artery disease (CAD) in EO patients has not been determined. This study evaluated the performance of Technetium-99m (Tc-99m) single photon emission computed tomography (SPECT) and rubidium-82 (Rb-82) positron emission tomography (PET) in patients with EO. METHODS: Weretrospectively identified all patientswith aBMI 40 kg/m who underwent angiography for evaluation of CAD in our centre between January 2007 and August 2010 and had been evaluated by either SPECT or PET within the previous six months.A cohort ofEOpatientswith a 50% and >70% as cutoffs. RESULTS: 108 patients who underwent Tc-99m SPECT (N 1⁄4 57, mean age 52.6 10.9, mean BMI 46.4 6.5) and Rb-82 PET (N1⁄4 51, mean age 50.0 11.4, mean BMI 45.6 5.0) were identified. 42/57 (73.7%) of SPECT studies used a two day protocol allowing a larger Tc-99m dose for better image quality. There were similar rates of angiographic multivessel disease (SPECT 15.8%, PET 15.7%) and left main coronary artery disease (SPECT 3.5%, PET 2.0%). Scan interpretation was classified as definitely normal or abnormal in 92.2% of PET and 66.7% of SPECT scans respectively (P 1⁄4 0.002). Using cutoffs of 50% and 70%, there were no significant differences in sensitivity, specificity, or diagnostic accuracy between the two modalities. At the 50% stenosis cutoff, there were trends towards increased specificity (SPECT 59.0% vs. PET 78.4%, P 1⁄4 0.087) and diagnostic accuracy (SPECT 61.4% and PET 78.4%, P 1⁄4 0.063) with PET. PET also demonstrated greater sensitivity in the detection of multivessel or left main coronary artery disease (SPECT 50% vs. PET 100%, P 1⁄4 0.036). CONCLUSIONS: InpatientswithEO,PETenabledmoredefinitive scan interpretation and providedhigher sensitivity in the detection ofmultivessel or leftmain coronary artery disease in comparison to SPECT. There was a trend towards increased specificity and diagnostic accuracy for PETrelative to SPECT.Basedon this data, PET may have added value in patients with EO.

Normal Myocardial Flow Reserve in HIV-Infected Patients on Stable Antiretroviral Therapy

Studies have found HIV-infected patients to be at increased risk of myocardial infarction, which may be caused by coronary microvascular dysfunction. For the first time among HIV-infected patients, we assessed the myocardial flow reserve (MFR) by Rubidium-82 (82Rb) positron emission tomography (PET), which can quantify the coronary microvascular function. MFR has proved highly predictive of future coronary artery disease and cardiovascular events in the general population.In a prospective cross-sectional study, HIV-infected patients all receiving antiretroviral therapy (ART) with full viral suppression and HIV-uninfected controls were scanned using 82Rb PET/computed tomography at rest and adenosine-induced stress, thereby obtaining the MFR (stress flow/rest flow), stratified into low ≤1.5, borderline >1.5 to 2.0, or normal >2.0.Fifty-six HIV-infected patients and 25 controls were included. The HIV-infected patients had a mean age of 53 years (range 37–68 years) with 23% active smokers. The controls had a mean age of 52 years (range 36–68 years) and 26% active smokers. In the HIV-infected group 73% had a normal MFR, 17% borderline, and 10% low values of MFR. Among controls these values were 71%, 19%, and 10%, respectively (P = 0.99). However, the HIV-infected group had lower values of stress myocardial blood flow (MBF) (2.63 ± 0.09 mL/g/min vs 2.99 ± 0.14 mL/g/min; P = 0.03). We found no evidence of decreased MFR as assessed by 82Rb PET among HIV-infected patients on stable ART with full viral suppression compared with HIV-uninfected controls. We did notice a decreased MBF during stress.

CORONARY ARTERY MICROVASCULAR DYSFUNCTION: ROLE OF SEX AND ARTERIAL LOAD

s S279 Young Investigator Award Winner e Clinical Science 528 CORONARY ARTERY MICROVASCULAR DYSFUNCTION: ROLE OF SEX AND ARTERIAL LOAD T Coutinho, L Mielniczuk, K Srivaratharajah, R deKemp, RS Beanlands

Basal hyperaemia is the primary abnormality of perfusion in Takotsubo cardiomyopathy: a quantitative cardiac perfusion positron emission tomography study.

Takotsubo cardiomyopathy (TTC) is characterized by acute completely reversible regional left ventricle (LV) akinesia and decreased tracer uptake in the akinetic region on semi-quantitative perfusion imaging. The latter may be due to normoperfusion of the akinetic mid/apical area and basal hyperperfusion. Our aim was to examine abnormalities of perfusion in TTC, and we hypothesized that basal hyperperfusion is the primary perfusion abnormality in the acute state. Twenty-five patients were diagnosed with TTC due to (i) acute onset of symptoms, (ii) typical apical ballooning, (iii) absence of significant coronary disease, and (iv) complete remission on 4-month follow-up. The patients underwent coronary angiography (CAG), echocardiography, cardiac magnetic resonance imaging (CMR), and (13)NH3/(82)Rb positron emission tomography (PET) in the acute state and-except CAG-on follow-up. Patients initially had severe heart failure, mid/apical oedema but no infarction, and a rise in cardiac biomarkers. On initial perfusion PET imaging, eight patients appeared to have normal, whereas 17 patients had impaired LV perfusion. In the latter, flow in the basal region was increased in the acute state (1.5 ± 0.1 vs. 1.2 ± 0.1 mL/g/minRPP-corrected, P < 0.01), whereas midventricular (1.7 ± 0.1 vs. 1.6 ± 0.1 mL/g/minRPP-corrected, P = 0.21) and apical (1.4 ± 0.1 vs. 1.5 ± 0.1 mL/g/minRPP-corrected, P = 0.36) flow was unchanged between acute and follow-up, and within normal range. Our results suggest an abnormal LV perfusion distribution in the acute state of TTC with basal hyperperfusion and a normoperfused akinetic region. The proportion of patients without visualized perfusion abnormalities in the acute state may represent a subgroup with fast remission.

Relationship of epicardial fat volume from noncontrast CT with impaired myocardial flow reserve by positron emission tomography

BackgroundImpaired myocardial flow reserve (MFR) is a marker of coronary vascular dysfunction with prognostic significance. ObjectivesWe aimed to investigate the relationship between epicardial fat volume (EFV) measured from noncontrast CT and impaired MFR derived from rest-stress Rb-82 positron emission tomography (PET). MethodsWe retrospectively studied 85 consecutive patients without known coronary artery disease who underwent rest-stress Rb-82 myocardial PET/CT and were subsequently referred for invasive coronary angiography. EFV was computed from noncontrast CT by validated software and indexed to body surface area (EFVi, cm3/m2). Global stress and rest MFR were automatically derived from PET. Patient age, sex, cardiovascular risk factors, coronary calcium score (CCS), and EFVi were combined by boosted ensemble machine learning algorithm into a novel composite risk score, using 10-fold cross-validation, to predict impaired global MFR (MFR ≤2.0) by PET. ResultsPatients with impaired MFR (44 of 85; 52%) were older (71 vs 65 years; P = .03) and had higher frequency of CCS (≥400; P = .02) with significantly higher EFVi (63.1 ± 20.4 vs 51.3 ± 14.1 cm3/m2; P = .003). On multivariate logistic regression (with age, sex, number of risk factors, CCS, and EFVi), EFVi was the only independent predictor of impaired MFR (odds ratio, 7.39; P = .02). The machine learning composite risk score significantly improved risk reclassification of impaired MFR compared to CCS or EFVi alone (integrated discrimination improvement = 0.19; P = .007 and IDI = 0.22; P = .002, respectively). ConclusionsIncreased EFVi and composite risk score combining EFVi and CCS significantly improve identification of impaired global MFR by PET.

Detection and severity classification of extracardiac interference in ⁸²Rb PET myocardial perfusion imaging.

Myocardial perfusion imaging (MPI) is used for diagnosis and prognosis of coronary artery disease. When MPI studies are performed with positron emission tomography (PET) and the radioactive tracer rubidium-82 chloride ((82)Rb), a small but non-negligible fraction of studies (∼10%) suffer from extracardiac interference: high levels of tracer uptake in structures adjacent to the heart which mask the true cardiac tracer uptake. At present, there are no clinically available options for automated detection or correction of this problem. This work presents an algorithm that detects and classifies the severity of extracardiac interference in (82)Rb PET MPI images and reports the accuracy and failure rate of the method. A set of 200 (82)Rb PET MPI images were reviewed by a trained nuclear cardiologist and interference severity reported on a four-class scale, from absent to severe. An automated algorithm was developed that compares uptake at the external border of the myocardium to three thresholds, separating the four interference severity classes. A minimum area of interference was required, and the search region was limited to that facing the stomach wall and spleen. Maximizing concordance (Cohen's Kappa) and minimizing failure rate for the set of 200 clinician-read images were used to find the optimal population-based constants defining search limit and minimum area parameters and the thresholds for the algorithm. Tenfold stratified cross-validation was used to find optimal thresholds and report accuracy measures (sensitivity, specificity, and Kappa). The algorithm was capable of detecting interference with a mean [95% confidence interval] sensitivity/specificity/Kappa of 0.97 [0.94, 1.00]/0.82 [0.66, 0.98]/0.79 [0.65, 0.92], and a failure rate of 1.0% ± 0.2%. The four-class overall Kappa was 0.72 [0.64, 0.81]. Separation of mild versus moderate-or-greater interference was performed with good accuracy (sensitivity/specificity/Kappa = 0.92 [0.86, 0.99]/0.86 [0.71, 1.00]/0.78 [0.64, 0.92]), while separation of moderate versus severe interference severity classes showed reduced sensitivity/Kappa but little change in specificity (sensitivity/specificity/Kappa = 0.83 [0.77, 0.88]/0.82 [0.77, 0.88]/0.65 [0.60, 0.70]). Specificity was greater than sensitivity for all interference classes. Algorithm execution time was <1 min. The algorithm produced here has a low failure rate and high accuracy for detection of extracardiac interference in (82)Rb PET MPI scans. It provides a fast, reliable, automated method for assessing severity of extracardiac interference.

The role of PET quantification in cardiovascular imaging.

Positron Emission Tomography (PET) has several clinical and research applications in cardiovascular imaging. Myocardial perfusion imaging with PET allows accurate global and regional measurements of myocardial perfusion, myocardial blood flow and function at stress and rest in one exam. Simultaneous assessment of function and perfusion by PET with quantitative software is currently the routine practice. Combination of ejection fraction reserve with perfusion information may improve the identification of severe disease. The myocardial viability can be estimated by quantitative comparison of fluorodeoxyglucose (18FDG) and rest perfusion imaging. The myocardial blood flow and coronary flow reserve measurements are becoming routinely included in the clinical assessment due to enhanced dynamic imaging capabilities of the latest PET/CT scanners. Absolute flow measurements allow evaluation of the coronary microvascular dysfunction and provide additional prognostic and diagnostic information for coronary disease. Standard quantitative approaches to compute myocardial blood flow from kinetic PET data in automated and rapid fashion have been developed for 13N-ammonia, 15O-water and 82Rb radiotracers. The agreement between software methods available for such analysis is excellent. Relative quantification of 82Rb PET myocardial perfusion, based on comparisons to normal databases, demonstrates high performance for the detection of obstructive coronary disease. New tracers, such as 18F-flurpiridaz may allow further improvements in the disease detection. Computerized analysis of perfusion at stress and rest reduces the variability of the assessment as compared to visual analysis. PET quantification can be enhanced by precise coregistration with CT angiography. In emerging clinical applications, the potential to identify vulnerable plaques by quantification of atherosclerotic plaque uptake of 18FDG and 18F-sodium fluoride tracers in carotids, aorta and coronary arteries has been demonstrated.

Prognostic Value of PET Myocardial Perfusion Imaging in Obese Patients

This study sought to determine and compare the prognostic and incremental value ofpositron emission tomography (PET) in normal, overweight, and obese patients. Cardiac rubidium 82 (Rb-82) PET is increasingly being used for myocardial perfusion imaging (MPI). A strength of PET is its accurate attenuation correction, thereby potentially improving its diagnostic accuracy in obese patients. The prognostic value of PET in obese patients has not been well studied. A total of 7,061 patients who had undergone Rb-82 PET MPI were entered into a multicenter observational registry. All patients underwent pharmacologic Rb-82 PET and were followed for cardiac death and all-cause mortality. Based on body mass index (BMI), patients were categorized as normal (<25 kg/m(2)), overweight (25 to 29.9 kg/m(2)), or obese (≥30 kg/m(2)). Using a 17-segment model and 5-point scoring system, the percentage of abnormal myocardium was calculated for stress and rest patients categorized as normal (0%), mild (0.1% to 9.9%), moderate (10% to 19.9%), and severe (≥20%). A total of 6,037 patients were followed for cardiac death (median: 2.2 years) and the mean BMI was 30.5 ± 7.4 kg/m(2). A total of 169 cardiac deaths were observed. PET MPI demonstrated independent and incremental prognostic value over BMI. Normal PET MPI conferred an excellent prognosis with very low annual cardiac death rates in normal (0.38%), overweight (0.43%), and obese (0.15%) patients. As well, both moderately and severe obese patients with a normal PET MPI had excellent prognosis (0.20% and 0.10%, respectively). The net reclassification improvement of PET was 0.46 (95% confidence interval [CI]: 0.31 to 0.61), and appeared similar in the moderately and severe obese patients which were 0.44 (95% CI: 0.12 to 0.76) and 0.63 (95% CI: 0.27 to 0.98), respectively. Rb-82 PET has incremental prognostic value in all patients irrespective of BMI. Inthe obese population, where other modalities may have reduced diagnostic accuracy, cardiac PETappears tobe a promising noninvasive modality with prognostic value.

Prognostic value of Rb-82 positron emission tomography myocardial perfusion imaging in coronary artery bypass patients

We sought to determine the prognostic value of positron emission tomography (PET) myocardial perfusion imaging (MPI) in patients with prior coronary artery bypass graft (CABG) surgery. PET MPI has recently been shown to provide incremental risk stratification for patients with suspected coronary artery disease (CAD), but the prognostic utility of PET MPI in CABG patients has not been well studied. A multi-centre PET registry of 7061 patients who underwent Rb-82 PET MPI from four participating centres was screened. Nine hundred and fifty-three CABG patients were identified and their images were analysed. Outcomes of all-cause mortality and cardiac death were collected. With a mean follow-up of 2.4 ± 1.4 years, 128 (13.4%) all-cause deaths and 44 (4.6%) cardiac deaths were observed. Multivariable analyses, adjusted for clinical variables, demonstrated that the summed stress score (SSS) was a significant independent predictor of both all-cause mortality [HR: 1.60 (per 1 category increase in SSS); 95% CI: 1.34-1.92; P < 0.001] and cardiac death (HR: 1.80; 95% CI: 1.33, 2.44; P < 0.001). The receiver-operator characteristic (ROC) curves showed that the addition of SSS increased the area under the curve (AUC) from 0.645 to 0.693 (P = 0.014) for all-cause mortality, and from 0.612 to 0.704 (P = 0.027) for cardiac death. SSS also improved the net reclassification improvement (NRI) for all-cause mortality (category-free NRI = 0.422; 95% CI: 0.240-0.603; P < 0.001) and cardiac death (category-free NRI = 0.552; 95% CI: 0.268-0.836; P < 0.001). PET MPI provides independent and incremental prognostic value to clinical variables in predicting all-cause mortality and cardiac death in CABG patients.

The relationship between ischemia-induced left ventricular dysfunction, coronary flow reserve, and coronary steal on regadenoson stress-gated 82Rb PET myocardial perfusion imaging

BackgroundGated rubidium-82 (82Rb) positron emission tomography (PET) imaging studies are acquired both at rest and during pharmacologic stress. Stress-induced ischemic left ventricular dysfunction (LVD) can produce a significant decrease in left ventricular ejection fraction (LVEF) from rest to stress. We determined the prevalence on PET of stress LVD with reduced ejection fraction (EF) and its association with absolute global and regional coronary flow reserve (CFR), and with relative perfusion defect summed difference score (SDS). Methods and ResultsWe studied 205 patients with known or suspected coronary disease (120 M, 75 F, age 69 ± 13 years) who had clinically indicated rest/regadenoson stress 82Rb PET/CT studies. Data were acquired in dynamic gated list mode. Global and 17-segment regional CFR values were computed from first-pass flow data using a 2-compartment model and factor analysis applied to auto-generated time-activity curves. Rest and stress LVEF and SDS were quantified from gated equilibrium myocardial perfusion tomograms using Emory Cardiac Toolbox software. LVD was defined as a change in LVEF of ≤−5% from rest to stress. A subgroup of 109 patients also had coronary angiography. Stress LVD developed in 32 patients (16%), with mean EF change of −10 ± 5%, vs +6 ± 7% for patients without LVD (P < .0001). EF was similar at rest in patients with and without stress LVD (57 ± 18% vs 56 ± 16%, P = .63), but lower during stress for patients with LVD (47 ± 20% vs 61 ± 16%, P = .0001). CFR was significantly lower in patients with LVD (1.61 ± 0.67 vs 2.21 ± 1.03, Wilcoxon P = .002), and correlated significantly with change in EF (r = 0.35, P < .0001), but not with SDS (r = −0.13, P = .07). The single variable most strongly associated with high risk of CAD (i.e., left main stenosis ≥50%, LAD % stenosis ≥70%, and/or 3-vessel disease) was stress EF (χ2 = 17.3, P < .0001). There was a higher prevalence of patients with territorial CFR values ≤1.0, consistent with coronary steal, in the LVD group than in the non-LVD group (39% vs 12%, P = .001). ConclusionsLVD developed in 16% of patients undergoing 82Rb PET myocardial perfusion imaging, and was associated with multivessel coronary artery disease. There was a significant relationship between LVD and coronary blood flow during stress, with LVD corresponding to a low CFR. Territorial CFR ≤1.0 was more common in patients with LVD than those without, suggesting that coronary steal is an important pathophysiologic mechanism contributing to pharmacologic stress-induced LVD.

Epicardial adipose tissue thickness as a predictor of impaired microvascular function in patients with non-obstructive coronary artery disease

ObjectiveTo determine if increased epicardial adipose tissue (EAT) measured by cardiac CT could be associated with impaired myocardial flow reserve (MFR) in patients with non-obstructive coronary artery disease (CAD). BackgroundStudies have shown that EAT volume is related to epicardial obstructive CAD, myocardial ischemia and major adverse cardiac events. However, the association between EAT with coronary microvascular dysfunction and impaired MFR has not been well clarified. MethodsConsecutive patients who underwent Rb-82 positron emission tomography (PET), coronary artery calcium (CAC) scoring and non-invasive coronary computed tomography angiography (CCTA) were screened. PET scans were analysed for standard myocardial perfusion (MPI) and MFR. CCTA results were analysed and only patients with non-obstructive CAD (<50% luminal diameter stenosis) were included. EAT thickness and volumes were measured from CT scans. ResultsOf 137 patients without obstructive CAD by CCTA and with normal Rb-82 PET relative MPI, 26 (19.0%) patients had impaired MFR < 2 and 87 (64%) patients had CAC. EATthickness, EATvolume and CAC values were higher in patients with impaired MFR < 2 than those with normal MFR ≥ 2 (6.7 ± 1.6 mm vs 4.4 ± 1.0 mm, P < .0001; 119.0 ± 25.3 cm3 vs 105.8 ± 30.5 cm3, P < .04 and 508.9 ± 554.3 vs 167.8 ± 253.9, P < .0001, respectively). However, EATthickness had a stronger negative correlation with MFR than EATvolume and CAC (r = −0.78 vs r = −0.25 and ρ = −0.32, P < .0001). With multivariable logistic regression analysis, only EATthickness was independently associated with impaired MFR (OR 20.7, 95% CI 4.9-87.9, P < .0001). Importantly, the receiver-operator characteristic (ROC) curves demonstrated a superior performance of EATthickness vs EATvolume and EATthickness vs CAC in detecting impaired MFR (AUC: 0.945 vs 0.625, difference between AUC: 0.319, P < .0001; AUC: 0.945 vs 0.710, difference between AUC: 0.235, P < .0006, respectively). On ROC curve analysis, an EATthickness cut-off value > 5.6 mm was optimal in detecting impaired MFR with a sensitivity and specificity of 81% and 92%, respectively. ConclusionsIncreased EAT appears to be associated with impaired MFR. This parameter may help improve detection of patients at risk of microvascular dysfunction.

Characterizing the normal range of myocardial blood flow with 82rubidium and 13N-ammonia PET imaging

BackgroundDiagnosis of coronary disease and microvascular dysfunction may be improved by comparing myocardial perfusion scans with a database defining the lower limit of normal myocardial blood flow and flow reserve (MFR). To maximize disease detection sensitivity, a small normal range is desirable. Both 13N-ammonia and 82Rb tracers are used to quantify blood flow and MFR using positron emission tomography (PET). The goal of this study was to investigate the trade-off between noise and accuracy in both 82Rb and 13N-ammonia normal databases formed using a net retention model. MethodsFourteen subjects with <5% risk of CAD underwent rest and stress 82Rb and 13N-ammonia dynamic PET imaging in a randomized order within 2 weeks. Myocardial blood flow was quantified using a one-compartment model for 82Rb, and a two-compartment model for 13N-ammonia. A simplified model was used to estimate tracer retention, with tracer-specific net extraction functions derived to obtain flow estimates. ResultsNormal variability of retention reserve was equivalent for both tracers (±15% globally, ±16% regionally) and was lower in comparison to compartment model results (P < .05). The two-compartment model for 13N-ammonia had the smallest normal range of global blood flow resulting in a lower limit of normal MFR = 2.2 (mean − 2 SD). ConclusionThese results suggest that the retention model may have higher sensitivity for detection and localization of abnormal flow and MFR using 82Rb and 13N-ammonia, whereas the 13N-ammonia two-compartment model has higher precision for absolute flow quantification.

Incremental diagnostic benefit of resolution recovery software in patients with equivocal myocardial perfusion single-photon emission computed tomography (SPECT)

BackgroundThough myocardial perfusion imaging (MPI) with single-photon emission computed tomography (SPECT) is an established diagnostic method, equivocal studies are commonly encountered. New software has been introduced that incorporates resolution recovery (RR) and noise regulation into the reconstruction algorithm and has been used to facilitate “half-dose” and “half-time” studies. Its utility with “full-time, full-dose” acquisition has not been well studied. ObjectiveWe sought to understand the potential benefit of incorporating RR software in equivocal SPECT studies. MethodsPatients with full-time, full-dose SPECT MPI were reviewed and those with equivocal results, who subsequently underwent cardiac Rb-82 positron emission tomography (PET) scan were identified. Image reconstruction was performed with iterative reconstruction (IR), attenuation correction (IR + AC), and RR software (IR + AC + RR). Images were anonymized and read blindly by consensus of two experienced readers. All images were qualitatively assessed and semi-quantitatively graded using summed stress and summed rest scores. Results45 patients were included (28 males, age = 59.6 ± 9.9 years) and the diagnostic accuracy of each of the reconstruction algorithms (IR, IR + AC, IR + AC + RR) was compared to Rb-82 PET. Agreement of clinical diagnosis of each SPECT reconstruction with Rb-PET showed incremental improvement. The agreement with PET for IR + AC + RR (κ = 0.66, CI 0.454-0.875) is significantly better than for IR (κ = 0.22, CI 0.0-0.450, P = .005) and for IR + AC (κ = 0.32, CI 0.077-0.563, P = .03). Also, IR + AC + RR improved the clinical diagnosis in 14 cases and with overall improvement of reclassification proportion of 23.5% compared to IR (P = .01). Using PET as a reference standard, ROC curves were created for IR + AC + RR, IR + AC, and IR which showed incremental value of the area under the curve of IR + AC + RR (AUC: 0.87; CI 0.76-0.98) over IR + AC (AUC: 0.75; CI 0.61-0.89, P = .078), and over IR (AUC 0.68; CI 0.52-0.84, P = .025). ConclusionThe addition of RR may help in the diagnosis of patients with equivocal SPECT MPI without the need for additional testing. Further prospective studies are needed to define the role of this new software.