[18F]Fluciclovine PET discrimination between high- and low-grade gliomas.

BACKGROUND: The ability to accurately and non-invasively distinguish high-grade glioma from low-grade glioma remains a challenge despite advances in molecular and magnetic resonance imaging. We investigated the ability of fluciclovine (18F) PET as a means to identify and distinguish these lesions in patients with known gliomas and to correlate uptake with Ki-67. RESULTS: Sixteen patients with a total of 18 newly diagnosed low-grade gliomas (n = 6) and high grade gliomas (n = 12) underwent fluciclovine PET imaging after histopathologic assessment. Fluciclovine PET analysis comprised tumor SUVmax and SUVmean, as well as metabolic tumor thresholds (1.3*, 1.6*, 1.9*) to normal brain background (TBmax, and TBmean). Comparison was additionally made to the proliferative status of the tumor as indicated by Ki-67 values. Fluciclovine uptake greater than normal brain parenchyma was found in all lesions studied. Time activity curves demonstrated statistically apparent flattening of the curves for both high-grade gliomas and low-grade gliomas starting 30 min after injection, suggesting an influx/efflux equilibrium. The best semiquantitative metric in discriminating HGG from LGG was obtained utilizing a metabolic 1 tumor threshold of 1.3* contralateral normal brain parenchyma uptake to create a tumor: background (TBmean1.3) cutoff of 2.15 with an overall sensitivity of 97.5% and specificity of 95.5%. Additionally, using a SUVmax > 4.3 cutoff gave a sensitivity of 90.9% and specificity of 97.5%. Tumor SUVmean and tumor SUVmax as a ratio to mean normal contralateral brain were both found to be less relevant predictors of tumor grade. Both SUVmax (R = 0.71, p = 0.0227) and TBmean (TBmean1.3: R = 0.81, p = 0.00081) had a high correlation with the tumor proliferative index Ki-67. CONCLUSIONS: Fluciclovine PET produces high-contrast images between both low-grade and high grade gliomas and normal brain by visual and semiquantitative analysis. Fluciclovine PET appears to discriminate between low-grade glioma and high-grade glioma, but must be validated with a larger sample size.

Association Between High-Sensitivity Cardiac Troponin Levels and Myocardial Ischemia During Mental Stress and Conventional Stress.

OBJECTIVES: This study sought to investigate whether patients with mental stress-induced myocardial ischemia will have high resting and post-mental stress high-sensitivity cardiac troponin I (hs-cTnI). BACKGROUND: Hs-cTnI is a marker of myocardial necrosis, and its elevated levels are associated with adverse outcomes. Hs-cTnI levels may increase with exercise in patients with coronary artery disease. Mental stress-induced myocardial ischemia is also linked to adverse outcomes. METHODS: In this study, 587 patients with stable coronary artery disease underwent technetium Tc 99m sestamibi-single-photon emission tomography myocardial perfusion imaging during mental stress testing using a public speaking task and during conventional (pharmacological/exercise) stress testing as a control condition. Ischemia was defined as new/worsening impairment in myocardial perfusion using a 17-segment model. RESULTS: The median hs-cTnI resting level was 4.3 (interquartile range [IQR]: 2.9 to 7.3) pg/ml. Overall, 16% and 34.8% of patients developed myocardial ischemia during mental and conventional stress, respectively. Compared with those without ischemia, median resting hs-cTnI levels were higher in patients who developed ischemia either during mental stress (5.9 [IQR: 3.9 to 8.3] pg/ml vs. 4.1 [IQR: 2.7 to 7.0] pg/ml; p < 0.001) or during conventional stress (5.4 [IQR: 3.9 to 9.3] pg/ml vs. 3.9 [IQR: 2.5 to 6.5] pg/ml; p < 0.001). Patients with high hs-cTnI (cutoff of 4.6 pg/ml for men and 3.9 pg/ml for women) had greater odds of developing mental (odds ratio [OR]: 2.4; 95% confidence interval [CI]: 1.5 to 3.9; p < 0.001) and conventional (OR: 2.4; 95% CI: 1.7 to 3.4; p < 0.001) stress-induced ischemia. Although there was a significant increase in 45-min post-treadmill exercise hs-cTnI levels in those who developed ischemia, there was no significant increase after mental or pharmacological stress test. CONCLUSIONS: In patients with coronary artery disease, myocardial ischemia during either mental stress or conventional stress is associated with higher resting levels of hs-cTnI. This suggests that hs-cTnI elevation is an indicator of chronic ischemic burden experienced during everyday life. Whether elevated hs-cTnI levels are an indicator of adverse prognosis beyond inducible ischemia or whether it is amenable to intervention requires further investigation.

Young women post-MI have higher plasma concentrations of interleukin-6 before and after stress testing.

OBJECTIVES: Young women have poorer prognosis after myocardial infarction (MI) and a higher rate of mental stress-induced ischemia compared with similarly aged men. A higher inflammatory status may help explain these sex differences. METHODS: We examined 98 patients (49 women and 49 men) age 18-59years with recent MI (past 6months). Women and men were matched for age, type of MI, and time since MI. Interleukin 6 (IL-6) concentrations were measured at baseline, after mental stress using a speech task, and after exercise/pharmacologic stress (60 and 90min). Depressive symptoms were measured with the Beck Depression Inventory (BDI-II) and angiographic coronary artery disease (CAD) severity was quantified with the Gensini score. Single-photon emission computed tomography (SPECT) was used to obtain a computerized measurement of stress-induced ischemia (summed difference score, or SDS) and determine whether severity of stress-induced ischemia affects the inflammatory response to stress. Analysis was stratified by the median age of 50. Geometric mean concentrations of IL-6 were obtained from general linear regression models. RESULTS: In both age groups, women had less angiographic CAD and a similar level of conventional risk factors compared with men. Despite this, baseline IL-6 geometric means before both mental and physical stress were twice as high in women ⩽50years of age compared to age-matched men (3.8 vs. 1.8pg/mL, p=0.001, across both conditions), while they were similar in women and men age >50years (2.3 vs. 2.2pg/mL, p=0.83). After mental stress, IL-6 concentrations increased in both women and men in a similar fashion and remained twice as high in women ⩽50years than men at both 60min (5.4 vs. 2.6pg/mL, p=0.002) and 90min (5.9 vs. 3.4pg/mL, p=0.01). No significant difference was found between women and men >50years of age at any time point after mental stress. Results were similar for physical stress. After accounting for SDS, IL-6 concentrations in young women remained higher after both mental and physical stress. Baseline IL-6 concentrations were not significantly related to inducible ischemia. CONCLUSIONS: After MI, young women aged 50years or younger, compared with age-matched men, have remarkably higher concentrations of inflammation at baseline and after both mental and physical stress, with a similar inflammatory response to both stressors. Sustained concentrations of inflammation in young women, not their response to stress, may contribute to their adverse outcomes post-MI.

Angina and mental stress-induced myocardial ischemia.

OBJECTIVE: Mental stress-induced myocardial ischemia is a common phenomenon in patients with coronary artery disease (CAD) and an emerging prognostic factor. Mental stress ischemia is correlated with ambulatory ischemia. However, whether it is related to angina symptoms during daily life has not been examined. METHODS: We assessed angina frequency (past month) in 98 post-myocardial infarction (MI) subjects (age 18-60 years) using the Seattle Angina Questionnaire. Patients underwent [(99m)Tc]sestamibi SPECT perfusion imaging at rest, after mental stress, and after exercise/pharmacological stress. Summed scores of perfusion abnormalities were obtained by observer-independent software. A summed difference score (SDS), the difference between stress and rest scores, was used to quantify myocardial ischemia under both stress conditions. RESULTS: The mean age was 50 years, 50% were female and 60% were non-white. After adjustment for age, sex, smoking, CAD severity, depressive, anger, and anxiety symptoms, each 1-point increase in mental stress-SDS was associated with 1.73-unit increase in the angina frequency score (95% CI: 0.09-3.37) and 17% higher odds of being in a higher angina frequency category (OR: 1.17, 95% CI: 1.00-1.38). Depressive symptoms were associated with 12% higher odds of being in a higher angina frequency category (OR: 1.12, 95% CI: 1.03-1.21). In contrast, exercise/pharmacological stress-induced SDS was not associated with angina frequency. CONCLUSION: Among young and middle-aged post-MI patients, myocardial ischemia induced by mental stress in the lab, but not by exercise/pharmacological stress, is associated with higher frequency of retrospectively reported angina during the day. Psychosocial stressors related to mental stress ischemia may be important contributory factor to daily angina.

Association between anger and mental stress-induced myocardial ischemia.

BACKGROUND: Mental stress-induced myocardial ischemia is associated with adverse prognosis in coronary artery disease patients. Anger is thought to be a trigger of acute coronary syndromes and is associated with increased cardiovascular risk; however, little direct evidence exists for a link between anger and myocardial ischemia. METHODS: [(99m)Tc]-sestamibi single-photon emission tomography was performed at rest, after mental stress (a social stressor with a speech task) and after exercise/pharmacologic stress. Summed scores of perfusion abnormalities were obtained by observer-independent software. A summed-difference score, the difference between stress and rest scores, was used to quantify myocardial ischemia under both stress conditions. The Spielberger's State-Trait Anger Expression Inventory was used to assess different anger dimensions. RESULTS: The mean age was 50 years, 50% were female, and 60% were non-white. After adjusting for demographic factors, smoking, coronary artery disease severity, depressive, and anxiety symptoms, each IQR increment in state-anger score was associated with 0.36 U-adjusted increase in ischemia as measured by the summed-difference score (95% CI 0.14-0.59); the corresponding association for trait anger was 0.95 (95% CI 0.21-1.69). Anger expression scales were not associated with ischemia. None of the anger dimensions was related to ischemia during exercise/pharmacologic stress. CONCLUSION: Anger, both as an emotional state and as a personality trait, is significantly associated with propensity to develop myocardial ischemia during mental stress but not during exercise/pharmacologic stress. Patients with this psychologic profile may be at increased risk for silent ischemia induced by emotional stress, and this may translate into worse prognosis.

Depressive symptoms are associated with mental stress-induced myocardial ischemia after acute myocardial infarction.

OBJECTIVES: Depression is an adverse prognostic factor after an acute myocardial infarction (MI), and an increased propensity toward emotionally-driven myocardial ischemia may play a role. We aimed to examine the association between depressive symptoms and mental stress-induced myocardial ischemia in young survivors of an MI. METHODS: We studied 98 patients (49 women and 49 men) age 38-60 years who were hospitalized for acute MI in the previous 6 months. Patients underwent myocardial perfusion imaging at rest, after mental stress (speech task), and after exercise or pharmacological stress. A summed difference score (SDS), obtained with observer-independent software, was used to quantify myocardial ischemia under both stress conditions. The Beck Depression Inventory-II (BDI-II) was used to measure depressive symptoms, which were analyzed as overall score, and as separate somatic and cognitive depressive symptom scores. RESULTS: There was a significant positive association between depressive symptoms and SDS with mental stress, denoting more ischemia. After adjustment for demographic and lifestyle factors, disease severity and medications, each incremental depressive symptom was associated with 0.14 points higher SDS. When somatic and cognitive depressive symptoms were examined separately, both somatic [ß = 0.17, 95% CI: (0.04, 0.30), p = 0.01] and cognitive symptoms [ß = 0.31, 95% CI: (0.07, 0.56), p = 0.01] were significantly associated with mental stress-induced ischemia. Depressive symptoms were not associated with ischemia induced by exercise or pharmacological stress. CONCLUSION: Among young post-MI patients, higher levels of both cognitive and somatic depressive symptoms are associated with a higher propensity to develop myocardial ischemia with mental stress, but not with physical (exercise or pharmacological) stress.

Sex differences in mental stress-induced myocardial ischemia in young survivors of an acute myocardial infarction.

OBJECTIVES: Emotional stress may disproportionally affect young women with ischemic heart disease. We sought to examine whether mental stress-induced myocardial ischemia (MSIMI), but not exercise-induced ischemia, is more common in young women with previous myocardial infarction (MI) than in men. METHODS: We studied 98 post-MI patients (49 women and 49 men) aged 38 to 60 years. Women and men were matched for age, MI type, and months since MI. Patients underwent technetium-99m sestamibi perfusion imaging at rest, after mental stress, and after exercise/pharmacological stress. Perfusion defect scores were obtained with observer-independent software. A summed difference score (SDS), the difference between stress and rest scores, was used to quantify ischemia under both stress conditions. RESULTS: Women 50 years or younger, but not older women, showed a more adverse psychosocial profile than did age-matched men but did not differ for conventional risk factors and tended to have less angiographic coronary artery disease. Compared with age-matched men, women 50 years or younger exhibited a higher SDS with mental stress (3.1 versus 1.5, p = .029) and had twice the rate of MSIMI (SDS ≥ 3; 52% versus 25%), whereas ischemia with physical stress did not differ (36% versus 25%). In older patients, there were no sex differences in MSIMI. The higher prevalence of MSIMI in young women persisted when adjusting for sociodemographic and life-style factors, coronary artery disease severity, and depression. CONCLUSIONS: MSIMI post-MI is more common in women 50 years or younger compared with age-matched men. These sex differences are not observed in post-MI patients who are older than 50 years.