Significant Association of Serum Albumin With the Severity of Coronary Microvascular Dysfunction Using Dynamic CZT-SPECT.

OBJECTIVE: Both low serum albumin (SA) concentration and coronary microvascular dysfunction (CMD) are risk factors for the development of heart failure (HF). We hypothesized that SA concentration is associated with myocardial flow reserve (MFR) and implicated in pathophysiological mechanism of HF. METHODS: We retrospectively studied 454 patients undergoing dynamic cardiac cadmium-zinc-telluride myocardial perfusion imaging from April 2018 to February 2020. The population was categorized into three groups according to SA level (g/dL): Group 1: >4, Group 2: 3.5-4, and Group 3: <3.5. Myocardial blood flow (MBF) and myocardial flow reserve (MFR, defined as stress/rest MBF ratio) were compared. RESULTS: The mean age of the whole cohort was 66.2 years, and 65.2% were men. As SA decreased, stress MBF (mL min-1 g-1) and MFR decreased (MBF: 3.29 ± 1.03, MFR: 3.46 ± 1.33 in Group 1, MBF: 2.95 ± 1.13, MFR: 2.51 ± 0.93 in Group 2, and MBF: 2.64 ± 1.16, MFR: 1.90 ± 0.50 in Group 3), whereas rest MBF (mL min-1 g-1) increased (MBF: 1.05 ± 0.42 in Group 1, 1.27 ± 0.56 in Group 2, and 1.41 ± 0.61 in Group 3). After adjusting for covariates, compared with Group 1, the odds ratios for impaired MFR (defined as MFR < 2.5) were 3.57 (95% CI: 2.32-5.48) for Group 2 and 34.9 (95% CI: 13.23-92.14) for Group 3. The results would be similar if only regional MFR were assessed. The risk prediction for CMD using SA was acceptable, with an AUC of 0.76. CONCLUSION: Low SA concentration was associated with the severity of CMD in both global and regional MFR as well as MBF.

Integrating subvolume dose and myocardial perfusion imaging parameters to assess the impact of radiation therapy on heart function in breast cancer patients: A comparative analysis between left- and right-sided breast cancer.

BACKGROUND: This study aimed to utilize an innovative method of integrating the 20 subvolume dose of left ventricle and the Tl-201 single photon emission computed tomography (SPECT) with myocardial perfusion imaging (MPI) parameters in patients with left- and right-sided breast cancer after radiation therapy. METHODS: Female patients with breast cancer underwent SPECT MPI before commencing radiotherapy and 12 months later were enrolled from January 2014 to December 2018. The images of CT simulation and SPECT MPI were integrated into the treatment planning system. The differences of doses and parameters of MPI in all cardiac subvolumes between left- and right-sided breast cancer patients were analyzed. RESULTS: Patients with left-sided breast cancer (n = 61) received a higher radiation dose to the heart, left ventricular, and its territories and subvolumes, compared to patients with right-sided breast cancer (n = 19). The 20-segment analysis also showed statistically significant disparities in the average radiation doses received by the two groups. In different coronary artery territories, the end-diastolic perfusion and end-systolic perfusion showed a decrease in both sides, with no significant differences. However, the wall motion and wall thickening showed a significant decline in subregions within the left- and right-sided coronary artery territories. CONCLUSION: This study demonstrates an innovative integrated method combining the left ventricular 20 regional doses with SPECT MPI which shows that left-sided breast cancer patients receive a higher subvolume dose than right-sided breast cancer patients. Further research is needed to confirm the potential impact on heart function after radiotherapy on both sides.

Evaluation of the cardiac subvolume dose and myocardial perfusion in left breast cancer patients with postoperative radiotherapy: a prospective study.

Adjuvant breast radiotherapy could reduce the risk of local recurrence. However, the radiation dose received by the heart also increases the risk of cardiotoxicity and causes consequential heart diseases. This prospective study aimed to evaluate more precisely cardiac subvolume doses and corresponding myocardial perfusion defects according to the American Heart Association (AHA)'s 20-segment model for single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) interpretation for breast cancer after radiotherapy. The 61 female patients who underwent adjuvant radiotherapy following breast cancer surgery for left breast cancer were enrolled. SPECT MPI were performed before radiotherapy for baseline study, and 12 months after for follow-up. Enrolled patients were divided into two groups, new perfusion defect (NPD) and non new perfusion defect found (non-NPD) according to myocardial perfusion scale score. CT simulation data, radiation treatment planning, and SPECT MPI images were fused and registered. The left ventricle was divided into four rings, three territories, and 20 segments according to the AHA's 20-segment model of the LV. The doses between NPD and non-NPD groups were compared by the Mann-Whitney test. The patients were divided into two groups: NPD group (n = 28) and non-NPD group (n = 33). The mean heart dose was 3.14 Gy in the NPD group and 3.08 Gy in the non-NPD group. Mean LV doses were 4.84 Gy and 4.71 Gy, respectively. The radiation dose of the NPD group was higher than the non-NPD group in the 20 segments of LV. There was significant difference in segment 3 (p = 0.03). The study indicated that the radiation doses to 20 segments of LV in NPD were higher than those in non-NPD significantly at segment 3, and higher in other segments in general. In the bull's eye plot combining radiation dose and NPD area, we found that the new cardiac perfusion decline may exist even in the low radiation dose region.Trial registration: FEMH-IRB-101085-F. Registered 01/01/2013, https://clinicaltrials.gov/ct2/show/NCT01758419?cond=NCT01758419&draw=2&rank=1 .

Treatment Resulting Changes in Volumes of High-18F-FDG-Uptake Adipose Tissues over Orbit and Epicardium Correlate with Treatment Response for Non-Hodgkin's Lymphoma.

BACKGROUND: A regimen of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is the standard treatment for non-Hodgkin's lymphoma. Brown adipose tissue possesses anti-cancer potential. This study aimed to explore practical biomarkers for non-Hodgkin's lymphoma by analyzing the metabolic activity of adipose tissue. METHODS: Twenty patients who received R-CHOP for non-Hodgkin's lymphoma were reviewed. Positron emission tomography/computed tomography (PET/CT) images, lactate dehydrogenase (LDH) levels, and body mass index (BMI) before and after treatment were collected. Regions with a high standardized uptake value (SUV) in epicardial and orbital adipose tissue were selected and analyzed by a PET/CT viewer. The initial measurements and changes in the high SUV of epicardial and orbital adipose tissues, LDH levels, and BMI of treatment responders and non-responders, and complete and partial responders, were compared. RESULTS: The volumes of high-SUV epicardial and orbital adipose tissues significantly increased in responders after R-CHOP (p = 0.03 and 0.002, respectively). There were significant differences between changes in the high-SUV volumes of epicardial and orbital adipose tissues (p = 0.03 and 0.001, respectively) and LDH levels (p = 0.03) between responders and non-responders. The changes in high-SUV epicardial adipose tissue volumes were greater among complete responders than partial responders (p = 0.04). Poorer treatment responses were observed in patients with lower high-SUV epicardial adipose tissue volumes and higher LDH levels after R-CHOP (p = 0.03 and 0.03, respectively). CONCLUSIONS: The preliminary results of greater changes in high-SUV epicardial and orbital adipose tissue volumes among responders indicate that brown adipose tissue could be considered a favorable prognostic biomarker.

Polar map-free 3D deep learning algorithm to predict obstructive coronary artery disease with myocardial perfusion CZT-SPECT.

PURPOSE: Deep learning (DL) models have been shown to outperform total perfusion deficit (TPD) quantification in predicting obstructive coronary artery disease (CAD) from myocardial perfusion imaging (MPI). However, previously published methods have depended on polar maps, required manual correction, and normal database. In this study, we propose a polar map-free 3D DL algorithm to predict obstructive disease. METHODS: We included 1861 subjects who underwent MPI using cadmium-zinc-telluride camera and subsequent coronary angiography. The subjects were divided into parameterization and external validation groups. We implemented a fully automatic algorithm to segment myocardium, perform registration, and apply normalization. We further flattened the image based on spherical coordinate system transformation. The proposed model consisted of a component to predict patent arteries and a component to predict disease in each vessel. The model was cross-validated in the parameterization group, and then further tested using the external validation group. The performance was assessed by area under receiver operating characteristic curves (AUCs) and compared with TPD. RESULTS: Our algorithm preprocessed all images accurately as confirmed by visual inspection. In patient-based analysis, the AUC of the proposed model was significantly higher than that for stress-TPD (0.84 vs 0.76, p < 0.01). In vessel-based analysis, the proposed model also outperformed regional stress-TPD (AUC = 0.80 vs 0.72, p < 0.01). The addition of quantitative images did not improve the performance. CONCLUSIONS: Our proposed polar map-free 3D DL algorithm to predict obstructive CAD from MPI outperformed TPD and did not require manual correction or a normal database.

Case report: Stereotactic body radiation therapy with 12 Gy for silencing refractory ventricular tachycardia.

Background: Encouraging results have been reported for the treatment of ventricular tachycardia (VT) with stereotactic body radiation therapy (SBRT) with 25 Gy. SBRT with 12 Gy for refractory VT was designed to reduce long-term cardiac toxicity. Methods: Stereotactic body radiation therapy-VT simulation, planning, and treatment were performed using standard techniques. A patient was treated with a marginal dose of 12 Gy in a single fraction to the planning target volume (PTV). The goal was for at least ≥ 95% of the PTV to be covered by at least 95% of 12 Gy radiation. Results: From April 2021 through June 2022, a patient with refractory VT underwent treatment. The volume for PTV was 65.8 cm3. The mean radiation dose administered to the heart (the heart volume excluding the PTV) was 2.2 Gy. No acute or late toxicity was observed after SBRT. Six months after SBRT, the patient experienced new monomorphic right ventricular outflow tract (RVOT) VT. Interestingly, the substrate of the left ventricular basal to middle posteroseptal wall before SBRT was turned into scar zones with a local voltage < 0.5 mV. Catheter ablation to treat RVOT VT was performed, and the situation remains stable to date. Conclusion: This study reports the first patient with refractory VT successfully treated with 12.0 Gy SBRT, suggesting that 12 Gy is a potential dose to treat refractory VT. Further investigations and enrollment of more patients are warranted to assess the long-term efficacy and side effects of this treatment.

Evaluation of the Key Advantages between Two Modalities of Boronophenylalanine Administration for Clinical Boron Neutron Capture Therapy Using an Animal Model.

In clinical boron neutron capture therapy (BNCT), boronophenylalanine (BPA) administrations through one-step infusion (OSI) and two-step infusion (TSI) are the most widely used. This study compared the advantages of OSI and TSI using a human oral squamous cell carcinoma-bearing animal model. OSI was administered at a high-dose rate of 20 mg/kg/min for 20 min (total dose: 400 mg/kg) as the first step infusion. TSI was a prolonged infusion at a low-dose rate of 1.67 mg/kg/min for 15, 30, 45, and 60 min (total dose: 25, 50, 75, and 100 mg/kg) following the first step infusion. The sigmoid Emax model was used to evaluate the boron accumulation effect in the tumor. The advantages of TSI were observed to be greater than those of OSI. The observed advantages of TSI were as follows: a stable level of boron concentration in blood; tumor to blood boron ratio (T/B); tumor to muscle boron ratio (T/M); and skin to blood boron ratio (S/B). The boron accumulation effect in tumors increased to 68.98%. Thus, effective boron concentration in these tumor cells was achieved to enhance the lethal damage in BNCT treatment. Boron concentration in the blood was equal to that in the skin. Therefore, the equivalent dose was accurately estimated for the skin.

Integrating 18 F-FDG PET/CT with lung dose-volume for assessing lung inflammatory changes after arc-based radiotherapy for esophageal cancer: A pilot study.

OBJECTIVE: The incidence of radiation pneumonitis (RP) has a highly linear relationship with low-dose lung volume. We previously established a volume-based algorithm (VBA) method to improve low-dose lung volume in radiotherapy (RT). This study assessed lung inflammatory changes by integrating fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (18 F-FDG PET/CT) with VBA for esophageal cancer patients undergoing arc-based RT. METHODS: Thirty esophageal cancer patients received 18 F-FDG PET/CT imaging pre-RT and post-RT were included in a retrospective pilot study. We fused lung doses and parameters of PET/CT in RT planning. Based on VBA, we used the 5Gy isodose curve to define high-dose (HD) and low-dose (LD) regions in the lung volume. We divided patients into non-RP (nRP) and RP groups. The maximum, mean standardized uptake value (SUVmax, SUVmean), global lung glycolysis (GLG), mean lung dose (MLD) and V5-30 in lungs were analyzed. Area under the curve values were utilized to identify optimal cut-off values for RP. RESULTS: Eleven patients in the nRP group and 19 patients in the RP group were identified. In 30 RP lungs, post-RT SUVmax, SUVmean and GLG of HD regions showed significant increases compared to values for pre-RT lungs. There were no significant differences in values of 22 nRP lungs. Post-RT SUVmax and SUVmean of HD regions, MLD, and lung V5 and V10 in RP lungs were significantly higher than in nRP lungs. For detecting RP, the optimal cut-off values were post-RT SUVmax > 2.28 and lung V5  > 47.14%. CONCLUSION: This study successfully integrated 18 F-FDG PET/CT with VBA to assess RP in esophageal cancer patients undergoing RT. Post-RT SUVmax > 2.28 and lung V5  > 47.14% might be potential indicators of RP.

Planning evaluation of a novel volume-based algorithm for personalized optimization of lung dose in VMAT for esophageal cancer.

Radiotherapy treatment planning (RTP) is time-consuming and labor-intensive since medical physicists must devise treatment plans carefully to reduce damage to tissues and organs for patients. Previously, we proposed the volume-based algorithm (VBA) method, providing optimal partial arcs (OPA) angle to achieve the low-dose volume of lungs in dynamic arc radiotherapy. This study aimed to implement the VBA for esophageal cancer (EC) patients and compare the lung dose and delivery time between full arcs (FA) without using VBA and OPA angle using VBA in volumetric modulated arc therapy (VMAT) plans. We retrospectively included 30 patients diagnosed with EC. RTP of each patient was replanned to 4 VMAT plans, including FA plans without (FA-C) and with (FA + C) dose constraints of OARs and OPA plans without (OPA-C) and with (OPA + C) dose constraints of OARs. The prescribed dose was 45 Gy. The OARs included the lungs, heart, and spinal cord. The dose distribution, dose-volume histogram, monitor units (MUs), delivery time, and gamma passing rates were analyzed. The results showed that the lung V5 and V10 in OPA + C plans were significantly lower than in FA + C plans (p < 0.05). No significant differences were noted in planning target volume (PTV) coverage, lung V15, lung V20, mean lung dose, heart V30, heart V40, mean heart dose, and maximal spinal cord dose between FA + C and OPA + C plans. The delivery time was significantly longer in FA + C plans than in OPA + C plans (237 vs. 192 s, p < 0.05). There were no significant differences between FA + C and OPA + C plans in gamma passing rates. We successfully applied the OPA angle based on the VBA to clinical EC patients and simplified the arc angle selection in RTP. The VBA could provide a personalized OPA angle for each patient and effectively reduce lung V5, V10, and delivery time in VMAT.

Integration of quantitative absolute myocardial blood flow estimates from dynamic CZT-SPECT improves the detection of coronary artery disease.

BACKGROUND: Balanced ischemia with multi-vessel coronary artery disease (CAD) is difficult to diagnose with semiquantitative single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI). Dynamic cardiac SPECT provides quantitative estimations of stenosis severity and ischemic burden by assessing myocardial flow reserve (MFR) and myocardial blood flow (MBF). The aim of this study was to evaluate the incremental value of dynamic SPECT in multi-vessel coronary artery disease (CAD). METHODS: Patients with suspected CAD who underwent dynamic ECG-gated dipyridamole MPI and coronary angiography within 6 months were retrospectively reviewed. The performance of summed stress, rest and difference scores (SSS, SRS, SDS), post-stress and resting MBF (MBFs, MBFr) and MFR were compared at both patient level and vessel level. RESULTS: In 32 patients with 39 stenotic vessels, 12 had three-vessel disease (38%). Globally increased SSS and impaired MBF values were significantly associated with significant CAD at the patient level, but SDS and MFR were not. Regional increases in SSS and reductions in both MBFs and MBFr were significantly associated with stenotic vessels. The best cutoff value of global MBFs to predict CAD was 3.5 ml·g-1·min-1 (area under the curve, AUC = .84, P = .002). The best cutoff value of regional MBFs to detect significant stenosis was 3.6 ml·g-1·min-1 (AUC = .74, P < .001). However, the best possible cut-off values of MFR were not found. Sex-difference in both global and regional MBFr but MBFs was found, which might result in the non-significance in MFR. CONCLUSIONS: This study validated a clinically available method to quantify MFR using dynamic CZT-SPECT. This method improved the detectability of multi-vessel CAD, and absolute MBFs was superior to MFR and other semiquantitative MPI parameters.

OncomiR miR-182-5p Enhances Radiosensitivity by Inhibiting the Radiation-Induced Antioxidant Effect through SESN2 in Head and Neck Cancer.

Radiotherapy is routinely used for the treatment of head and neck squamous cell carcinoma (HNSCC). However, the therapeutic efficacy is usually reduced by acquired radioresistance and locoregional recurrence. In this study, The Cancer Genome Atlas (TCGA) analysis showed that radiotherapy upregulated the miR-182/96/183 cluster and that miR-182 was the most significantly upregulated. Overexpression of miR-182-5p enhanced the radiosensitivity of HNSCC cells by increasing intracellular reactive oxygen species (ROS) levels, suggesting that expression of the miR-182 family is beneficial for radiotherapy. By intersecting the gene targeting results from three microRNA target prediction databases, we noticed that sestrin2 (SESN2), a molecule resistant to oxidative stress, was involved in 91 genes predicted in all three databases to be directly recognized by miR-182-5p. Knockdown of SESN2 enhanced radiation-induced ROS and cytotoxicity in HNSCC cells. In addition, the radiation-induced expression of SESN2 was repressed by overexpression of miR-182-5p. Reciprocal expression of the miR-182-5p and SESN2 genes was also analyzed in the TCGA database, and a high expression of miR-182-5p combined with a low expression of SESN2 was associated with a better survival rate in patients receiving radiotherapy. Taken together, the current data suggest that miR-182-5p may regulate radiation-induced antioxidant effects and mediate the efficacy of radiotherapy.

2021 Advocacy Statements for the Role of 99mTc-Pyrophosphate Scintigraphy in the Diagnosis of Transthyretin Cardiac Amyloidosis: A Report of the Taiwan Society of Cardiology and the Society of Nuclear Medicine of the Republic of China.

Transthyretin cardiac amyloidosis (ATTR-CM) is an increasingly recognized cause of heart failure with preserved ejection fraction. Favorable prognosis depends on early diagnosis and correct treatment strategy. Among patients for whom there is a high clinical suspicion of cardiac amyloidosis, 99mTc-labeled bone avid scintigraphy including 99mTc-pyrophosphate (PYP) scintigraphy may be of diagnostic and prognostic importance. Various international guidelines support the non-biopsy diagnosis of ATTR-CM using 99mTc-PYP scintigraphy, yet emphasize the gap in standardization of acquisition and imaging analysis protocols, as well as the appropriateness of its clinical use. Therefore, a joint expert consensus has been reached by the Taiwan Society of Cardiology and the Society of Nuclear Medicine of the Republic of China, to advocate for the application of 99mTc-PYP scintigraphy in the diagnosis of ATTR-CM. This article aims to highlight the recommendations on image acquisition, qualitative and quantitative assessments of cardiac 99mTc-PYP uptake, and diagnostic algorithms. We hope the implementation of these recommendations in Taiwan will facilitate the process and enhance the diagnostic rate of ATTR-CM.

Volume-based algorithm of lung dose optimization in novel dynamic arc radiotherapy for esophageal cancer.

This study aims to develop a volume-based algorithm (VBA) that can rapidly optimize rotating gantry arc angles and predict the lung V5 preceding the treatment planning. This phantom study was performed in the dynamic arc therapy planning systems for an esophageal cancer model. The angle of rotation of the gantry around the isocenter as defined as arc angle (θA), ranging from 360° to 80° with an interval of 20°, resulting in 15 different θA of treatment plans. The corresponding predicted lung V5 was calculated by the VBA, the mean lung dose, lung V5, lung V20, mean heart dose, heart V30, the spinal cord maximum dose and conformity index were assessed from dose-volume histogram in the treatment plan. Correlations between the predicted lung V5 and the dosimetric indices were evaluated using Pearson's correlation coefficient. The results showed that the predicted lung V5 and the lung V5 in the treatment plan were positively correlated (r = 0.996, p < 0.001). As the θA decreased, lung V5, lung V20, and the mean lung dose decreased while the mean heart dose, V30 and the spinal cord maximum dose increased. The V20 and the mean lung dose also showed high correlations with the predicted lung V5 (r = 0.974, 0.999, p < 0.001). This study successfully developed an efficient VBA to rapidly calculate the θA to predict the lung V5 and reduce the lung dose, with potentials to improve the current clinical practice of dynamic arc radiotherapy.

Biokinetic model of radioiodine I-131 in nine thyroid cancer patients subjected to in-vivo gamma camera scanning: A simplified five-compartmental model.

A five-compartmental biokinetic model of I-131 radioiodine based on in-vivo gamma camera scanning results was developed and successfully applied to nine thyroid cancer patients who were administered 1,110 MBq I-131 in capsules for the residual thyroid gland ablation. The I-131 solution activity among internal organs was analyzed via the revised biokinetic model of iodine recommended by the ICRP-30 and -56 reports. Accordingly, a five-compartmental (stomach, body fluid, thyroid, whole body, and excretion) model was established to simulate the metabolic mechanism of I-131 in thyroid cancer patients, whereas the respective four simultaneous differential equations were solved via a self-developed program run in MATLAB. This made it possible to provide a close correlation between MATLAB simulation results and empirical data. The latter data were collected through in-vivo gamma camera scans of nine patients obtained after 1, 4, 24, 48, 72, and 168 hours after radioactive I-131 administration. The average biological half-life values for the stomach, body fluid, thyroid, and whole body of thyroid cancer patients under study were 0.54±0.32, 12.6±1.8, 42.8±5.1, and 12.6±1.8 h, respectively. The corresponding branching ratios I12, I23, I25, I34, I42, and I45 as denoted in the biokinetic model of iodine were 1.0, 0.21±0.14, 0.79±0.14, 1.0, 0.1, and 0.9, respectively. The average values of the AT dimensionless index used to verify the agreement between empirical and numerical simulation results were 0.056±0.017, 0.017±0.014, 0.044±0.023, and 0.045±0.009 for the stomach, thyroid, body fluid + whole body, and total, respectively. The results obtained were considered quite instrumental in the elucidation of metabolic mechanisms in the human body, particularly in thyroid cancer patients.

The clinical usefulness of phase analysis in detecting coronary artery disease using dipyridamole thallium-201-gated myocardial perfusion imaging with a cadmium-zinc-telluride camera.

BACKGROUND: Previous studies have demonstrated left ventricular mechanical dyssynchrony (LVMD) in patients with severe coronary artery disease (CAD) with ≥ 70% stenosis. The aim of this study was to evaluate the clinical usefulness of stress/rest LVMD in the diagnosis of CAD with ≥ 50% stenosis using dipyridamole thallium-201 (Tl-201) myocardial perfusion imaging (MPI) with a cadmium-zinc-telluride camera. METHODS AND RESULTS: A total of 476 patients without known CAD who underwent dipyridamole Tl-201 MPI and coronary angiography within 6 months were retrospectively reviewed. LVMD parameters including phase standard deviation and phase histogram bandwidth, phase skewness and phase kurtosis, as well as myocardial perfusion and myocardial stunning were assessed in post-stress and rest MPI. Relationships between the presence of CAD on coronary angiography and single photon emission computerized tomography (SPECT) parameters were evaluated. The presence of perfusion abnormalities was the best diagnostic tool in detecting CAD. Although less left ventricular synchrony was observed post-stress in the CAD group compared to the non-CAD group, no significant dyssynchrony was noted. CONCLUSIONS: The addition of phase analysis to help diagnose CAD in Tl-201-gated SPECT with dipyridamole stress may have limited value in patients with CAD with ≥ 50% stenosis.

Clinical significance of quantitative assessment of glucose utilization in patients with ischemic cardiomyopathy.

BACKGROUND: The aim of this study was to prospectively quantify the rate of myocardial glucose uptake (MRGlu) in myocardium with different perfusion-metabolism patterns and determine its prognostic value in patients with ischemic cardiomyopathy. METHODS AND RESULTS: 79 patients with ischemic cardiomyopathy were prospectively enrolled for dynamic cardiac FDG PET, and then followed for at least 6 months. Perfusion-metabolism patterns were determined based on visual score analysis of 201Tl SPECT and FDG PET. MRGlu was analyzed using the Patlak kinetic model. The primary end-point was cardiovascular mortality. Significantly higher MRGlu was observed in viable compared with non-viable areas. Negative correlations were found between MRGlu in transmural match and a history of hyperlipidemia, statin usage, and triglyceride levels. Diabetic patients receiving dipeptidyl peptidase-4 inhibitors (DPP4i) had a significantly lower MRGlu in transmural match, mismatch, and reverse mismatch. Patients with MRGlu in transmural match ≥ 23.40 or reverse mismatch ≥ 36.90 had a worse outcome. CONCLUSIONS: Myocardial glucose utilization was influenced by substrates and medications, including statins and DPP4i. MRGlu could discriminate between viable and non-viable myocardium, and MRGlu in transmural match and reverse mismatch may be prognostic predictors of cardiovascular death in patients with ischemic cardiomyopathy.

Clinical significance of quantitative assessment of right ventricular glucose metabolism in patients with heart failure with reduced ejection fraction.

PURPOSE: Dynamic 18F-fluorodeoxyglucose (FDG) PET can be used to quantitatively assess the rate of myocardial glucose uptake (MRGlu). The aim of this study was to evaluate the clinical significance and prognostic value of right ventricular (RV) MRGlu in patients with coronary artery disease and heart failure with reduced ejection fraction. METHODS: Patients with left ventricular ejection fraction (LVEF) ≤ 40% were consecutively enrolled for FDG PET between November 2012 and May 2017. Global LV and RV MRGlu (µmol/min/100 g) were analyzed. Outcome events were independently assessed using electronic medical records to determine hospitalization for revascularization, new-onset ischemic events, heart failure, cardiovascular, and all-cause death. Differences between LV and RV MRGlu and associations with clinical characteristics and echocardiographic data were evaluated. Associations among FDG PET findings and outcomes were analyzed using Kaplan-Meier survival analysis. RESULTS: Seventy-five patients (mean age 62.2 ± 12.7 years, male 85.3%, LVEF 19.3 ± 8.6%) were included for analysis. The mean glucose utilization ratio of RV-to-LV (RV/LV MRGlu) was 89.5 ± 264.9% (r = 0.77, p < 0.001). Positive correlations between RV MRGlu and maximal tricuspid regurgitation peak gradient (r = 0.28, p = 0.033) and peak tricuspid regurgitation jet velocity (r = 0.29, p = 0.021) were noted. LVEF was positively correlated with LV MRGlu (r = 0.27, p = 0.018), but negatively correlated with end-diastolic volume (r = - 0.37, p = 0.001), end-systolic volume (r = - 0.54, p < 0.001), and RV/LV MRGlu (r = - 0.40, p < 0.001). However, RV MRGlu was not well correlated with LVEF. Forty-three patients received revascularization procedures after FDG PET, and 13 patients died in a mean follow-up period of 496 ± 453 days (1-1788 days), including nine cardiovascular deaths. Higher RV and LV MRGlu values, LVEF ≤ 16% and LV end-diastolic volume ≥ 209 ml of gated-PET were associated with poor overall survival and cardiac outcomes. CONCLUSIONS: In patients with coronary artery disease and ischemic cardiomyopathy, RV glucose utilization was positively correlated with RV pressure overload, but not LVEF. Global LV and RV MRGlu, LVEF, and LV end-diastolic volume showed significant prognostic value.