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DOE OSTI2019

The correlation between the incidence of adverse events and progression-free survival in patients treated with cabozantinib for metastatic renal cell carcinoma (mRCC)

Clinical practice shows significant differences in treatment outcomes across patients treated with cabozantinib for metastatic renal cell carcinoma (mRCC). It is not known whether cabozantinib-induced adverse events are predictive factors of survival as in case of drugs such as sunitinib or axitinib. The study participants were 30 adult patients with mRCC treated with cabozantinib as a second- or further line setting. All adverse events were evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Progression-free survival (PFS) values were calculated by taking the beginning of cabozantinib treatment as the start date and either disease progression or death as the end date. PFS were estimated using the Kaplan–Meier method, and compared using the log-rank test. We identified independent PFS predictors using multiple Cox proportional hazards models and reported hazard ratios (HR) with 95% confidence intervals. The median observation time cabozantinib treatment was 7.5 months, with a range of 2–15 months. During that time, 11 (37%) of the patients had mRCC progression. Median PFS on cabozantinib was not reached, and lower quartile was 6 months. All patients developed at least one adverse event in the course of cabozantinib therapy. Hypertension, hypothyroidism and HFS were observed most frequently, in about two-thirds of the patients. The co-incidence of multiple adverse events was common. Hypertension, hypothyroidism, diarrhea and liver toxicity were significantly associated with longer PFS values. Patients with three or more side effects had significantly longer PFS than those with two or fewer. Even though this study was conducted in a small patient sample and the observation time was relatively short our results confirm the predictive value of the incidence of adverse events during cabozantinib treatment in mRCC patients. To the best of our knowledge, this is the first study of this kind conducted in this group of patients.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

DOE OSTI2019

Evaluating the decisions of glioma patients regarding clinical trial participation: a retrospective single provider review

Clinical trial accrual is vital to advancing care. A single study elucidated demographic data correlating with glioma patients’ clinical trial enrollment. However, it did not investigate the underlying decision-making process for non-participation. In this study, we seek to understand this key aspect of patient accrual. All notes for glioma patients seen by a single neuro-oncologist from July 2010 to May 2017 were examined for mention of clinical trial offerings. When a trial was declined, the patient’s reasoning was recorded along with the following: diagnosis, KPS, extent of resection, age, gender, race, marital status, income group, religion, trial offered at initial visit versus subsequent, and distance from trial site. Of 279 consecutive glioma patients, 88 were eligible for and offered a clinical trial. Fifty-seven accepted (65%), and 31 (35%) declined participation (Fig. 1). Of those offered a clinical trial, patients with glioblastoma (GBM) were significantly more likely to accept (44 out of 57 (77%) vs. 13 out of 57 (23%), p =0.03). After we adjusted for gender and travel distance, GBM was the only significant predictor of clinical trial acceptance, with an odds ratio of 3.18 (95% CI 1.17, 8.61, p =0.02). Reasons cited for non-participation included: travel distance (39%), lack of interest (39%), visit frequency (16%), and fear of randomization (6%). This study clarified for the first time individual glioma patient rationale for non-participation and potential areas for improving enrollment. Allowing off-site treatment centers or telemedicine visits may entice rural patients to participate. Visit frequency should be carefully considered and minimized whenever possible. Further prospective study of rationale for non-participation may improve enrollment over time.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

DOE OSTI2019

Altered fibrin clot properties in advanced lung cancer: strong impact of cigarette smoking

Background: Dense fibrin networks resistant to lysis have been reported in patients at high risk of thromboembolism. Little is known about fibrin clot properties in cancer. We investigated fibrin clot properties and their determinants in patients with inoperable lung cancer. Methods: We enrolled 150 patients with advanced lung cancer prior to therapy and 90 control subjects matched by age, sex, cardiovascular disease, and diabetes. Plasma clot permeability (K{sub s}), turbidimetric analysis of clot formation, clot lysis time (CLT), microparticle-associated tissue factor (MP-TF) activity, thrombin generation, and serum cotinine levels were determined. Results: Lung cancer patients, compared with controls, formed at a faster rate (− 8.1% lag phase) denser plasma fibrin networks (− 27.2% K{sub s}) that displayed impaired lysis (+ 26.5% CLT), along with 19.5% higher MP-TF activity and 100% higher peak thrombin generated, also after adjustment for potential confounders. Cotinine levels were associated with fibrin maximum absorbance (r = 0.20, p = 0.016) and K{sub s} (r = − 0.50, p < 0.0001) in cancer patients. On multivariate regression analysis, an increase in cotinine levels was a predictor of low K{sub s} (the lower quartile, < 5.8 × 10{sup −9} cm{sup 2}; odds ratio = 1.21 per 10 ng/ml, 95% confidence interval 1.02–1.46), but not CLT. Conclusion: Advanced lung cancer is associated with the prothrombotic plasma clot phenotype largely driven by smoking.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

DOE OSTI2019

Postmastectomy radiation therapy using VMAT technique for breast cancer patients with expander reconstruction

Postmastectomy radiotherapy (PMRT) following immediate breast reconstruction is increasingly adopted in the management of breast cancer patients. We retrospectively evaluate the complication rates of PMRT using VMAT technique to immediate tissue expander-based reconstructions and the possible impact of tissue expander volume on radiotherapy planning. We reviewed the data of patients who underwent immediate expander breast reconstruction and received PMRT with VMAT (50 Gy in 25 fractions) on the reconstructed breast and axillary levels III–IV. Neoadjuvant or adjuvant systemic therapy was administered in most of the patients. Autologous fat grafting was routinely performed at the time of second-stage reconstruction. Between 2015 and 2017, PMRT was delivered to 46 consecutive patients (median age 50 years) with expander reconstruction. Median follow-up was 27 months (range 10–41). Two patients (4.3%) had a reconstruction failure, as expander rupture and infection, following the first- and the second-stage reconstruction, respectively. In most cases expanders were completely inflated before PMRT (65.2%). Median expander volume before PMRT was 425 cm{sup 3} (range 150–700 cm{sup 3}). The amount of expander inflation did not significantly affect dosimetry, except for skin dose, with a surface receiving more than 30 Gy of 36.6 ± 0.9 cm{sup 2} and 47.0 ± 2.5 cm{sup 2} for a volume expander below or above the median, respectively. However, this variable was not predictor for complications. Disease progression was recorded in 15.2% of patients. PMRT using VMAT technique for breast cancer patients with expander reconstruction is associated with a very low complication rate. The expander volume before PMRT does not significantly compromise radiotherapy dose distribution.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

DOE OSTI2019

Recurrent prostate cancer after radical prostatectomy: restaging performance of 18F-choline hybrid PET/MRI

To evaluate the diagnostic performance of a whole-body 18F-choline (FCH) hybrid PET/MRI for prostate cancer patients at biochemical relapse after radical prostatectomy (RP) compared to pelvic multiparametric MRI (mpMRI), one of the standard imaging modality for this patient population. From 2010 to 2016, 58 whole-body FCH PET/MRI studies with mpMRI acquisitions were performed in 53 prostate cancer patients relapsing after curative RP. Median PSA and PSA doubling time (PSA DT) at PET study were 1.5 ng/ml and 6.5 months, respectively. The overall positivity rate of FCH PET/MRI was 58.6% (n = 34), dropping to 44% in patients with a PSA ≤ 2 ng/ml (n = 36). Median PSA values in positive and negative PET/MRI studies were 2.2 ng/ml and 0.8 ng/ml, respectively, with no differences in PSA DT (6.5 vs. 6.6 months). A PSA value ≥ 1.5 ng/ml was a significant predictor of positivity on PET/MRI studies. Compared to PET, mpMRI identified more local relapses (17 vs. 14, p = 0.453) while PET outperformed whole-body Dixon MRI for regional (16 vs. 9, p = 0.016) and distant (12 vs. 6, p = 0.031) metastases. Compared to pelvic mpMRI, the treatment approach turned out to be influenced more frequently using whole-body FCH hybrid PET/MRI studies (58.6% vs. 38%). In prostate cancer patients with biochemical recurrence after RP, whole-body FCH PET/MRI achieved a higher detection rate of nodal/distant metastases compared to pelvic mpMRI alone, increasing the change of treatment strategy by more than 20%.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

DOE OSTI2014

Quantitative trait loci (QTL) underlying biomass yield and plant height in switchgrass

Switchgrass (Panicum virgatum L.) biomass yield and feedstock quality improvement are priority research areas for bioenergy feedstock development. Identification of quantitative trait loci (QTL) underlying these traits and of trait-linked markers for application in marker-assisted selection (MAS) is of paramount importance in facilitating switchgrass breeding. Detection of QTL for biomass yield and plant height was conducted on parental linkage maps constructed using a heterozygous pseudo-F-1 population derived from a cross between lowland Alamo genotype AP13 and upland Summer genotype VS16. QTL analysis was performed with composite interval mapping. Four QTL for biomass yield and five QTL for plant height were identified using best linear unbiased predictors across ten and eight environments, respectively. The phenotypic variability explained (PVE) by QTL detected in the across environments analysis ranged from 4.9 to 12.4 % for biomass yield and 5.1 to 12.0 % for plant height. A total of 34 and 38 main effect QTL were detected for biomass yield and plant height, respectively, when data from each environment were analyzed separately. The PVE by individual environment QTL ranged from 3.3 to 15.3 % for biomass yield and from 4.3 to 17.4 % for plant height. In addition, 60 and 51 epistatic QTL were detected for biomass yield and plant height, respectively. Significant QTL by environment interactions were detected for QTL mapped in eight genomic regions for each of the two traits. Seven QTL affected both traits and may represent pleiotropic loci. Overall, 11 genomic regions were identified that were important in controlling biomass yield and/or plant height in switchgrass. Furthermore, the markers linked to the main effect and epistatic QTL may be used in MAS to maximize selection gain in switchgrass breeding, leading to a faster development of better biofuel cultivars.

09 BIOMASS FUELS↗

DOE OSTI2017

An assessment of the safety, hemodynamic response, and diagnostic accuracy of commonly used vasodilator stressors in patients with severe aortic stenosis

Background: Increasing numbers of patients are undergoing transcatheter aortic valve replacement, which often involves assessment of coronary artery disease ischemic burden. The safety and diagnostic accuracy of vasodilator stress agents in patients with severe aortic stenosis (AS) undergoing SPECT myocardial perfusion imaging (MPI) has not been established. Methods: Patients with severe AS (valve area <1 cm{sup 2}) on echocardiography who underwent vasodilator stress SPECT MPI at two centers were identified. Patients with aortic valve intervention prior to MPI or who underwent concurrent exercise during stress testing were excluded. AS patients were matched to controls without AS based on age, gender, BMI, ejection fraction, and stress agent. Symptoms, serious adverse events, hemodynamic response, and correlation to invasive angiography were assessed. Results: A total of 95 cases were identified with 45% undergoing regadenoson, 31% dipyridamole, and 24% adenosine stress. A significant change in systolic blood pressure (BP), cases vs controls, was observed with adenosine [−17.9 ± 20.1 vs −2.6 ± 24.9 P = .03)], with a trend toward significance with regadenoson [−16.8 ± 20.3 vs −9.4 ± 17.9 (P = .08)] and dipyridamole [−17.8 ± 20.6 vs -9.0 ± 12.1 (P = .05)]. The change in heart rate was significantly different only for adenosine [5.3 ± 16.8 vs 14.2 ± 10.8 (P = .04)]. Overall, 45% of cases vs 24% of controls (P = .004) had a >20 mmHg decrease in systolic BP. Age, BMI, and resting systolic BP were related to a >20 mmHg decrease in systolic BP on univariate analysis, although only higher resting systolic BP was a predictor on multivariate analysis. In 33 patients who underwent angiography, the sensitivity, specificity, and diagnostic accuracy of vasodilator stress MPI was 77%, 69%, and 73%, respectively. No serious adverse events occurred in the severe AS patients. Conclusion: Severe AS patients are more likely to have a hemodynamically significant decrease in systolic BP with vasodilator stress. There were no serious adverse events in this severe AS cohort with good diagnostic performance of MPI compared to angiography.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

DOE OSTI2017

Impact of cardiac reverse remodeling after cardiac resynchronization therapy assessed by myocardial perfusion imaging on ventricular arrhythmia

Background: Although cardiac resynchronization therapy (CRT) has been a useful treatment of heart failure, patients with CRT are still in risk of sudden cardiac death due to ventricular arrhythmia. The aim of this study was to investigate the impact of cardiac reverse remodeling after CRT on the prevalence of ventricular tachycardia or fibrillation (VT/VF). Methods and Results: Forty-one heart failure patients (26 men, age 66 ± 10 years), who were implanted with CRT for at least 12 months, were enrolled. All patients received myocardial perfusion imaging (MPI) under CRT pacing to evaluate left ventricle (LV) function, dyssynchrony, and scar. VT/VF episodes during the follow-up period after MPI were recorded by the CRT devices. Sixteen patients (N = 16/41, 39%) were found to have VT/VF. Multivariate Cox regression analysis and receiver operating characteristic curve analysis showed that five risk factors were significant predictors of VT/VF, including increased left ventricle ejection fraction (LVEF) by ≤7% after CRT, low LVEF after CRT (≤30%), change of intrinsic QRS duration (iQRSd) by ≤7 ms, wide iQRSd after CRT (≥121 ms), and high systolic dyssynchrony after CRT (phase standard deviation ≥45.6°). For those patients with all of the 5 risk factors, 85.7% or more developed VT/VF. Conclusions: The characteristics of cardiac reverse remodeling after CRT as assessed by MPI are associated with the prevalence of ventricular arrhythmia.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

DOE OSTI2017

Type 2 diabetes mellitus correlates with systolic function during myocardial stress perfusion scanning with Nitrogen-13 ammonia PET

Background: The influence of type 2 diabetes mellitus (DM2) on systolic function is partially determined by the coronary vasodilator function, nevertheless, an independent effect is suspected. We evaluated the relationship between DM2 and systolic function considering PET quantitative myocardial perfusion. Methods: We analyzed 585 patients without a previous myocardial infarction referred to a rest and adenosine stress Nitrogen-13 ammonia PET. A bootstrapped multiple linear regression analysis was performed using DM2, stress myocardial blood flow (sMBF), myocardial perfusion reserve (MPR), and clinical risk factors as predictors and LVEF as the outcome variable; an interaction term was additionally investigated. Results: Two hundred and ninety male and 295 female patients (mean age 65.3 ± 9.9 and 67.4 ± 10 years, respectively) were included. 57.1% presented hypertension, 16% smoking, 37.6% hypercholesterolemia, 33.8% family history for CAD, and 15.2% DM2. The mean MPR was 2.13 ± 0.48 and 2.21 ± 0.60, mean sMBF was 2.01 ± 0.51 and 2.15 ± 0.54, and mean LVEF was 63% ± 10.4 and 67% ± 10.1 for diabetics and non-diabetics, respectively. A significant relation was detected for sMBF (B = 5.830 95% CI [3.505, 9.549], P = .001) and DM2 (B = −2.599 95% CI [−5.125, −0.119], P = .03) with LVEF. The interaction (DM2 × sMBF) yielded no significance (P = .512). Conclusion: DM2 influences PET-measured systolic function in patients without previous myocardial infarction independently from myocardial perfusion parameters. Our study supports the importance of DM2 as an independent risk factor for deteriorating systolic function.

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DOE OSTI2019

Prognostic value of left ventricular dyssynchrony evaluated by gated myocardial perfusion imaging in patients with chronic kidney disease and normal perfusion defect scores

Background: This study aimed to investigate whether indices of left ventricular (LV) dyssynchrony by gated myocardial perfusion SPECT (GMPS) could be useful to predict prognosis in chronic kidney disease (CKD) patients with normal perfusion defect scores. Methods: One hundred and sixty-seven CKD patients with normal perfusion defect scores on adenosine-stress {sup 201}Tl GMPS and no previous history of overt heart diseases were enrolled. Phase standard deviation (PSD) and bandwidth (BW) were automatically calculated from GMPS. The major adverse cardiac events (MACEs) for a mean of 560 days were defined as sudden cardiac death, fatal arrhythmias, and acute coronary syndrome requiring urgent coronary revascularization. Patients were divided into two groups according to the presence or absence of MACEs. Results: The MACEs occurred in 12 patients (7.1%). Patients who experienced MACEs showed significantly higher PSD and wider BW than those who did not. In the Kaplan-Meier event-free survival analysis, cardiac event rate was significantly higher in the high-PSD and wide-BW group (n = 81) than in the low-PSD and narrow-BW group (n = 71) (P = .002). The multivariate regression analysis revealed that the PSD was associated with MACEs (odds ratio 1.33, 95% confidence interval 1.05-1.69, P = .01). Conclusion: The LV dyssynchrony indices from GMPS may be novel prognostic predictors in CKD patients with normal perfusion defect scores.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

DOE OSTI2018

Assessment of left ventricular contraction patterns using gated SPECT MPI to predict cardiac resynchronization therapy response

Background: The U-shaped left ventricular (LV) contraction pattern, identified by MRI or echocardiography, is associated with improved CRT response. Gated SPECT MPI can measure both myocardial viability and mechanical dyssynchrony in a single scan. The aim of this study is to examine the relationship of the LV contraction pattern and the response of CRT in patients with left bundle branch block (LBBB). Methods: Fifty-eight patients who met CRT guidelines and who had pre-CRT MPI were enrolled. Myocardial segments with tracer uptake < 50% of maximum were considered as scar. The LV contraction pattern was considered as U-shaped or non-U-shaped (U-shaped has a block line in the direction of contraction propagation). CRT response was defined as an increase in left ventricular ejection fraction ≥ 5% after 6-month follow-up. Results: Twenty-eight patients (48%) had a U-shaped contraction pattern and thirty patients (52%) had a non-U-shaped contraction pattern. The U-shaped group showed a significantly higher response rate than the non-U-shaped group (90% vs. 57%; P = 0.005). By univariate and multivariate logistic regression analysis, the U-shaped pattern was an independent predictor of CRT response. Conclusion: Non-invasive gated SPECT MPI can characterize LV mechanical contraction patterns. A U-shaped contraction pattern identified is associated with improved CRT response. This may prove useful for improved patient selection for CRT.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

DOE OSTI2019

Relationship of non-invasive quantification of myocardial blood flow to arrhythmic events in patients with implantable cardiac defibrillators

Background: Ischemia contributes to arrhythmogenesis though its role is incompletely understood. Abnormal myocardial perfusion measured by PET imaging may predict ventricular arrhythmias (VAs) in a high-risk population. Methods: Patients with implantable cardiac defibrillators who had undergone rubidium-82 cardiac PET imaging were identified. Patients were stratified by median MBF and MFR values for analysis. The Cox proportional hazards model was used to assess the impact of myocardial perfusion on survival free of VT independent of critical covariates. Results: A total of 159 patients (124 (78%) males, median age 65.9 years, IQR [56.76-72.63]) were followed for 1.43 years IQR [0.83-2.21]. VA occurred in 29 patients (23.7%). After adjustment for ejection fraction, age, and sex, impaired stress MBF was associated with an increased risk of VA (adjusted HR per ml/min/g 1.52, 95% CI (1.01-2.31), P = 0.04). Summed rest and stress scores were not predictive of VA. Among patients with severe LV dysfunction, stress MBF remained an independent predictor of VA (adjusted HR per 1 ml/min/g HR 1.69, 95% CI (1.03-11.36), P = 0.03), while residual EF, summed rest, and summed stress scores were not (P > 0.05). Conclusions: Impaired stress myocardial blood flow was associated with less survival free of ventricular arrhythmias.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

DOE OSTI2019

Predictive value of {sup 18}F-FDG PET/CT in patients with acute type B aortic intramural hematoma

Background: The clinical course and predictors of adverse aortic events (AAE) in patients with acute Stanford type B intramural hematoma (IMH) remain controversial. This study aimed to investigate whether {sup 18}F-FDG PET/CT can predict risk in patients with acute type B IMH. Methods and Results: This study included 34 patients with acute type B IMH who underwent PET/CT within 14 days from the onset of symptoms. The maximal standardized uptake values (SUVmax) of {sup 18}F-FDG uptake was significantly different between patients with or without AAE (4.3 ± 0.6 vs 3.7 ± 1.0, P = 0.020), but not the target to blood ratio (TBR, SUVmax divided by SUV in the superior vena cava) (1.6 ± 0.2 vs 1.5 ± 0.5, P = 0.064). In patients with initial ulcer-like projection (ULP), a blood-filled pouch protruding into the IMH, which was seen in 25 patients(74%), both the SUVmax and TBR were significantly higher in patients who developed AAE, (4.3 ± 0.6 vs 3.3 ± 0.5, P = 0.001; 1.6 ± 0.2 vs 1.4 ± 0.2, P = 0.01); the TBR >1.5, which is determined from receiver-operating-characteristic curve, had a sensitivity of 73% and a specificity of 80% in predicting AAE. Conclusion: Patients with ULP and high {sup 18}F-FDG uptake were more likely to develop AAE and may require closer surveillance with serial imaging.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

DOE OSTI2019

Interactions between myocardial sympathetic denervation and left ventricular mechanical dyssynchrony: A CZT analysis

Background: A correlation between left ventricular (LV) dyssynchrony (LVD) and impaired myocardial sympathetic tone has been hypothesized. We sought to assess the interactions between regional LV sympathetic innervation, perfusion, and mechanical dyssynchrony. Methods: Eighty-three patients underwent evaluation of LV perfusion and sympathetic innervation on {sup 99m}Tc-tetrofosmin/{sup 123}I-metaiodobenzylguanidine ({sup 123}I-MIBG) imaging. The summed rest score and summed {sup 123}I-MIBG score (SS-MIBG) were computed. The extent of “innervation/perfusion” mismatch was defined as the number of denervated LV segments with relatively preserved perfusion. LVD was evaluated on phase analysis and the wall with latest mechanical activation identified. Results: LVD was revealed in 36 (43%) patients. Patients with LVD had more abnormal values of SRS (21 ± 9 vs 10 ± 8, P < 0.001) and SS-MIBG (29 ± 9 vs 17 ± 11, P < 0.001) than those without LVD. The presence of LVD also clustered with a higher burden of “innervation/perfusion” mismatch (P = 0.019). On per-wall analysis, LV walls with delayed mechanical activation showed a higher burden of “innervation/perfusion” mismatch (2.3 ± 1.4 segments) than normally contracting walls (1.3 ± 1.2 segments; P < 0.001). On multivariate analysis, the extent of “innervation/perfusion” mismatch was the only predictor of delayed mechanical activation (P = 0.029). Conclusions: Patients with LVD show an elevated burden of “innervation/perfusion” mismatch that is concentrated at the level of the most dyssynchronous walls.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

DOE OSTI2019

Coronary calcium score influences referral for invasive coronary angiography after normal myocardial perfusion SPECT

Background: In patients with normal SPECT but persistent complaints, invasive angiography may exclude obstructive coronary disease. We assessed whether high coronary artery calcium (CAC) scores are associated with increased referral for invasive angiography following normal SPECT. Methods and results: 2286 consecutive patients (mean age 60 ± 12, 39% male) with normal SPECT were assessed. All patients underwent simultaneous CAC scoring. Patients were categorized into four groups based on their CAC score: CAC = 0 (n = 694), CAC 1 to 100 (n = 891), CAC 101 to 400 (n = 368), and CAC >400 (n = 333). The decision to perform angiography was left to the discretion of treating physician. Follow-up angiography was confined to the first 60 days after SPECT. Occurrence of MACE (late revascularization, myocardial infarction or death) was recorded. Overall, 100 patients (4.4%) underwent early angiography with increasing rates in higher CAC score groups (1.0%, 2.6%, 8.4%, and 11.7%), respectively, P < .001). A CAC score >400 (OR 3.56, 95% CI 2.19 to 5.77, P < .001) was independently associated with referral to angiography. Similarly, CAC score >400 was an independent predictor for MACE (HR 9.26, 95% CI 5.06 to 16.93). Early angiography did not influence prognosis (HR 1.57, 95% CI 0.91 to 2.73). Conclusions: CAC scoring impacts clinical decision-making and increases referral rates for invasive angiography after normal SPECT.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

DOE OSTI2019

Prediction of long-term (> 10 year) cardiovascular outcomes in heart transplant recipients: Value of stress technetium-99m tetrofosmin myocardial perfusion imaging

Background: Myocardial perfusion imaging (MPI) using single-photon emission computed tomography (SPECT) is useful in the evaluation of cardiac allograft vasculopathy (CAV) in heart transplant (HTx) recipients. The current study evaluated the long-term prognostic value of stress SPECT MPI for predicting all-cause mortality and cardiac events in HTx recipients. Methods: The study population consisted of 166 HTx recipients (mean age 54 ± 10 years, 84% male) who underwent exercise or dobutamine stress {sup 99m}Tc-tetrofosmin SPECT MPI for the assessment of CAV. An abnormal SPECT MPI was defined as the presence of a fixed or a reversible perfusion defect. Endpoints were all-cause mortality, cardiac mortality, and non-fatal myocardial infarction (MI). Results: MPI abnormalities were detected in 55 patients (33%), including fixed defects in 28 patients (17%), partially reversible in 17 patients (10%), and completely reversible defects in 10 patients (6%). During a median follow-up of 12.8 years (range 0-15, mean follow-up 9.5 years), 109 (66%) patients died (all-cause mortality), of which 67 (40%) were due to cardiac causes. A total of 5 (3%) patients experienced a non-fatal MI. HTx recipients with a normal stress {sup 99m}Tc-tetrofosmin SPECT MPI had a significantly better prognosis as compared with those with an abnormal study, up to 5 years after the initial test. The presence of a reversible perfusion defect was a significant predictor of all-cause mortality, cardiac mortality, and major cardiac events, during the entire follow-up period. Conclusions: Stress {sup 99m}Tc-tetrofosmin SPECT MPI provides valuable prognostic information for the prediction of long-term outcome in HTx recipients. Patients with a normal stress {sup 99m}Tc-tetrofosmin SPECT MPI have a significantly better prognosis as compared with those with an abnormal study, up to 5 years after initial testing.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

DOE OSTI2019

Added prognostic value of left ventricular shape by gated SPECT imaging in patients with suspected coronary artery disease and normal myocardial perfusion

Background: Left ventricular (LV) remodeling is associated with adverse cardiovascular events. We evaluated the added prognostic value of LV shape index (SI) assessed by gated single-photon emission tomography (SPECT) in patients without known coronary artery disease (CAD). Methods and results: We studied 674 patients with normal myocardial perfusion and normal LV ejection fraction (EF) on stress gated SPECT imaging. An automated software program was used to calculate end-diastolic and end-systolic LVSI. An LVSI ≤ 0.54 at end-systole was considered normal. Follow-up was 96% complete with a median follow-up of 37 months. During follow-up, 25 events occurred (3.8% cumulative event rate). Event-free survival was lower in patients with abnormal end-systolic LVSI (P < .001). Age (P = .021), diabetes (P = .048), and end-systolic LVSI (P < .001) were independent predictors of events. LVSI added prognostic information increasing the global chi-square of the model including age and diabetes from 15.15 to 25.97 (P < .001). The effect of diabetes on hazard ratio increased with increasing values of end-systolic LVSI. The probability of events at 48 months predicted by Weibull analysis progressively increased with increasing values of end-systolic LVSI and was higher in patients with diabetes as compared to those without. Decision curve analyses indicate that the model including end-systolic LVSI resulted in an increased net benefit between 5% and 30% threshold probability, indicating superior estimation of outcomes at low threshold probability levels. Conclusions: The evaluation of LVSI may identify patients with early-stage LV remodeling and at higher risk of adverse cardiac events, even in the presence of normal myocardial perfusion.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

DOE OSTI2019

Complete revascularization determined by myocardial perfusion imaging could improve the outcomes of patients with stable coronary artery disease, compared with incomplete revascularization and no revascularization

Objectives: To compare the outcomes among patients treated by complete coronary revascularization (CCR) or incomplete coronary revascularization (ICR) and no coronary revascularization (NCR) by myocardial perfusion imaging (MPI), as well as to evaluate the impact of severity of ischemia on patients with coronary artery disease (CAD) by different therapy strategies. Background: Using myocardial ischemia severity determined by MPI guiding treatment strategies for CAD patients still lacks strong clinical evidences. Methods: Consecutive patients (N = 286) underwent clinical stress-rest SPECT MPI and were retrospectively followed-up. For assessment of outcome of treatment, all patients were classified into three groups (CCR, ICR, and NCR), and further divided into two subgroups as mild ischemia (< 10% ischemic myocardium) and moderate-severe ischemia (≥ 10% ischemic myocardium). All-cause death was defined as the primary endpoint, and the composite of deaths, nonfatal myocardial infarction, and repeat revascularization (MACE) as the secondary endpoint. Results: Two-hundred eighty-six patients were followed-up for 46 ± 21 months. Thirty deaths and 65 MACEs were recorded. Patients treated by revascularization had significantly lower MACE (P < .001) but not mortality (P = .158) than patients treated by NCR. Outcomes of CCR related to mortality rate were greater than ICR and NCR (death: P = .019, MACE: P < .001). In patients with moderate-severe ischemia, CCR showed improved outcomes than ICR and NCR (death: P = .034; and MACE: P < .001). In patients with mild ischemia, the outcomes of CCR, ICR, and NCR had no significant difference (P > .05). Multivariate regression Cox analysis revealed that summed difference score [death: HR 1.09 (1.03, 1.15), P = .004] was an independent risk factor and CCR was an independent negative predictor [death: HR 0.31 (0.12, 0.81), P = .017; MACE: HR 0.30 (0.16, 0.57), P < .001]. Conclusions: Outcomes of patients treated by CCR were most likely more promising in comparison with treatment of ICR and NCR, especially when patients had over 10% ischemic myocardium.

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