Mental Stress-Induced Change in Plasma Stromal Cell-Derived Factor-1 and Adverse Cardiovascular Outcomes: A Cohort Study.

Background: Acute psychological stress can provoke mental stress-induced myocardial ischemia (MSIMI) in coronary artery disease (CAD). Stromal cell-derived factor 1 (SDF1) is released in response to hypoxia, and higher levels of SDF1 are associated with adverse outcomes. We examined whether an increase in SDF1 level in response to mental stress predicts adverse outcomes in CAD patients. Methods: A total of 554 patients with stable CAD (mean age 63 years; 76% male; 26% Black) underwent standardized mental stress testing. Plasma SDF1 levels were measured at rest and 90 minutes after mental stress, and MSIMI was evaluated by 99mTc-sestamibi perfusion imaging. Participants were followed for 5 years for the primary endpoint of composite of death and myocardial infarction (MI) and the secondary endpoint of composite of death, MI, and heart failure hospitalization. Cox hazard models were used to assess the association between SDF1 change and incident adverse events. Results: Mean (standard deviation) SDF1 change with mental stress was +56.0 (230) pg/mL. During follow-up, a rise of 1 standard deviation in SDF1 with mental stress was associated with a 32% higher risk for the primary endpoint of death and MI (95% confidence interval, 6%-64%), independent of the resting SDF1 level, demographic and clinical risk factors, and presence of ischemia. A rise of 1 standard deviation in SDF1 was associated with a 33% (95% confidence interval, 11%-59%) increase in the risk for the secondary endpoint, independent of the resting SDF1 level, demographic, and clinical risk factors and presence of ischemia. Conclusions: An increase in SDF1 level in response to mental stress is associated with a higher risk of adverse events in stable CAD, independent of MSIMI.

Contexte: Un stress psychologique aigu peut provoquer une ischémie myocardique induite par le stress mental chez les patients atteints d'une coronaropathie. Le facteur dérivé des cellules stromales de type 1 (SDF1) est libéré en réponse à une hypoxie, et des taux accrus de SDF1 sont associés à des résultats défavorables. Nous avons examiné si une élévation des taux de SDF1 en réponse à un stress mental permettait de prévoir la survenue de résultats défavorables chez des patients atteints d'une coronaropathie. Méthodologie: Au total, 554 patients présentant une coronaropathie stable (âge moyen de 63 ans; 76 % d'hommes; 26 % de patients de race noire) ont subi une évaluation standardisée du stress mental. Les taux plasmatiques de SDF1 ont été mesurés au repos et 90 minutes après un stress mental, et l'ischémie myocardique induite par le stress mental a été évaluée par imagerie avec injection de Tc-99m sestamibi. Les participants ont fait l'objet d'un suivi pendant cinq ans afin de surveiller la survenue des événements constituant le paramètre d'évaluation principal composé (décès et infarctus du myocarde [IM]) et le paramètre d'évaluation secondaire composé (décès, IM et hospitalisation en raison d'une insuffisance cardiaque). Des modèles de Cox ont été utilisés pour évaluer le lien entre la modification des taux de SDF1 et les événements indésirables susceptibles de survenir. Résultats: La variation moyenne du taux de SDF1 (écart-type) associée au stress mental a été de +56,0 (230) pg/ml. Pendant le suivi, une augmentation de 1 écart-type du taux de SDF1 en raison du stress mental a été associée à un risque 32 % plus élevé de survenue de l'un des événements constituant le paramètre d'évaluation principal (décès et IM) [intervalle de confiance [IC] à 95 % : 6 % à 64 %], indépendamment du taux de SDF1 au repos, des caractéristiques démographiques, des facteurs de risque clinique et de la présence d'une ischémie. Une augmentation de 1 écart-type du taux de SDF1 a été associée à un risque 33 % plus élevé (IC à 95 % : 11 % à 59 %) de survenue de l'un des événements constituant le paramètre d'évaluation secondaire, indépendamment du taux de SDF1 au repos, des caractéristiques démographiques, des facteurs de risque clinique et de la présence d'une ischémie. Conclusions: Une augmentation du taux de SDF1 en réponse à un stress mental est associée à une augmentation du risque d'événements indésirables chez les patients atteints d'une coronaropathie stable, indépendamment de la présence d'une ischémie myocardique induite par le stress mental.

Neural correlates of stress and leucocyte telomere length in patients with coronary artery disease.

BACKGROUND: Accelerated biological aging, as indicated by telomere shortening, is associated with CAD pathogenesis. In a cross-sectional study, we investigated neural correlates of acute psychological stress and short telomeres in patients with CAD. METHODS: Individuals with CAD (N = 168) underwent a validated mental stress protocol including public speaking and mental arithmetic. Imaging of the brain with [O-15] water and high-resolution positron emission tomography (HR-PET) was performed during mental stress and control conditions. Blood flow during stressful tasks (average of speech and arithmetic) and control tasks were assessed. Telomere length in peripheral leucocytes was measured by quantitative polymerase chain reaction and expressed as Telomere/Single Copy Gene (T/S) ratio. Voxel-wise regression models were constructed to assess the association between brain areas and activity during rest and mental stress after adjustments for demographic factors and clinical characteristics. RESULTS: The mean (SD) age of the sample was 62 (8) years, and 69% were men. Increased activation with mental stress in the lingual gyrus, cerebellum and superior and inferior frontal gyri were associated with reduced telomere length; 1.6 higher voxel activation of these areas was associated with 0.1 T/S-units reduction in telomere length (P < 0.005). Additionally, during neutral counting and speaking tasks, brain activity in the precentral, middle and superior frontal and middle temporal gyri was inversely associated with telomere length. Results remained consistent after adjustment for demographic and clinical risk factors. CONCLUSION: Increased stress-induced activity in brain areas mediating the stress response was associated with shortened telomere length in CAD patients.

Novel PET and Near Infrared Imaging Probes for the Specific Detection of Bacterial Infections Associated With Cardiac Devices.

OBJECTIVES: The aim of this study was to develop imaging agents to detect early stage infections in implantable cardiac devices. BACKGROUND: Bacteria ingest maltodextrins through the specific maltodextrin transporter. We developed probes conjugated with either a fluorescent dye (maltohexaose fluorescent dye probe [MDP]) or a F-18 (F18 fluoromaltohexaose) and determined their usefulness in a model of infections associated with implanted cardiac devices. METHODS: Stainless steel mock-ups of medical devices were implanted subcutaneously in rats. On post-operative day 4, animals were injected with either Staphylococcus aureus around the mock-ups to induce a relatively mild infection or oil of turpentine to induce noninfectious inflammation. Animals with a sterile implant were used as control subjects. On post-operative day 6, either the MDP or F18 fluoromaltohexaose was injected intravenously, and the animals were scanned with the appropriate imaging device. Additional positron emission tomography imaging studies were performed with F18-fluorodeoxyglucose as a comparison of the specificity of our probes (n = 5 to 9 per group). RESULTS: The accumulation of the MDP in the infected rats was significantly increased at 1 h after injection when compared with the control and noninfectious inflammation groups (intensity ratio 1.54 ± 0.07 vs. 1.26 ± 0.04 and 1.20 ± 0.05, respectively; p < 0.05) and persisted for more than 24 h. In positron emission tomography imaging, both F18 fluoromaltohexaose and F18 fluorodeoxyglucose significantly accumulated in the infected area 30 min after the injection (maximum standard uptake value ratio 4.43 ± 0.30 and 4.87 ± 0.28, respectively). In control rats, there was no accumulation of imaging probes near the device. In the noninfectious inflammation rats, no significant accumulation was observed with F18 fluoromaltohexaose, but F18 fluorodeoxyglucose accumulated in the mock-up area (maximum standard uptake value 2.53 ± 0.39 vs. 4.74 ± 0.46, respectively; p < 0.05). CONCLUSIONS: Our results indicate that maltohexaose-based imaging probes are potentially useful for the specific and sensitive diagnosis of infections associated with implantable cardiac devices.

Quantitative outcome of registration methods for correcting cardiac drift in cardiac PET/CT imaging.

Myocardial perfusion studies suffer from artifacts caused by misalignment of the transmission and emission data due to the influences of voluntary and involuntary patient motion. Regardless of 68Ge or respiratory-averaged CT based attenuation correction and good patient cooperation, approximately 21% of perfusion studies exhibit artifacts arising from misalignment that cannot be corrected by manipulating the attenuation acquisition protocol. This misalignment, termed cardiac drift, is caused by slow-moving abdominal cavity contents that reposition the heart in the thorax and appear as myocardial uptake overlying the left CT lung in fused PET/CT images. This study evaluates three postimaging registration techniques to correct PET/CT misalignment by altering the transmission map to match myo-cardial uptake. Simulated misalignment studies were performed with a cardiac torso phantom filled with [18F]FDG at 10:1 myocardium/background. An air-filled saline bag affixed to the medial left lung surface served as a distensible lung. An initial CT acquisition was followed by successive PET acquisitions consisting of small displacements of the cardiac insert into the left lung. Phantom transmission scans were aligned to the myocardial uptake in the emission scans by applying 1) full rigid-body translations and rotations, 2) rigid-body restricted to medial / lateral and superior / inferior translation, or 3) an emission-driven method that adds myocardial tissue to the transmission scan. These methods were also applied to 10 low-likelihood coronary artery disease (CAD) patients showing signs of cardiac drift. Full rigid-body registration showed significant over-correction (p < 0.004) of activity concentrations in the artifact areas of the phantom data due the relocation of highly attenuating structures (i.e., spine). Inaccurate regional activity distributions were also observed as streaks extending from the spine and these results were replicated in the patient population. There was no significant difference between the true phantom activity concentration after correction with the emission-driven method. Misalignment corrected with the rigid-body registration results in an increase in activity concentration but fails to accurately recover the true concentration. These data suggest that a nonlinear image registration approach such as an emission-driven method results in a more uniform activity distribution throughout the myocardium, and is more appropriate for addressing the cardiac drift misalignment problem.

Accuracy Evaluation of a 3D Ultrasound-guided Biopsy System.

Early detection of prostate cancer is critical in maximizing the probability of successful treatment. Current systematic biopsy approach takes 12 or more randomly distributed core tissue samples within the prostate and can have a high potential, especially with early disease, for a false negative diagnosis. The purpose of this study is to determine the accuracy of a 3D ultrasound-guided biopsy system. Testing was conducted on prostate phantoms created from an agar mixture which had embedded markers. The phantoms were scanned and the 3D ultrasound system was used to direct the biopsy. Each phantom was analyzed with a CT scan to obtain needle deflection measurements. The deflection experienced throughout the biopsy process was dependent on the depth of the biopsy target. The results for markers at a depth of less than 20 mm, 20-30 mm, and greater than 30 mm were 3.3 mm, 4.7 mm, and 6.2 mm, respectively. This measurement encapsulates the entire biopsy process, from the scanning of the phantom to the firing of the biopsy needle. Increased depth of the biopsy target caused a greater deflection from the intended path in most cases which was due to an angular incidence of the biopsy needle. Although some deflection was present, this system exhibits a clear advantage in the targeted biopsy of prostate cancer and has the potential to reduce the number of false negative biopsies for large lesions.

Prompt-gamma compensation in Rb-82 myocardial perfusion 3D PET/CT.

OBJECTIVE: To compare the diagnostic accuracy of Rb-82 myocardial perfusion three-dimensional (3D) PET with and without prompt-gamma compensation (PGC). METHODS AND RESULTS: Retrospective, single center study of 76 patients who had rest and adenosine stress Rb-82 myocardial perfusion 3D PET. All studies were acquired using a Siemens Biograph-40 PET/CT scanner and were reconstructed with and without PGC. Fifty-seven patients (mean age 63 +/- 11 years, 26 men) had coronary angiography within 40 days of Rb-82 imaging. Nineteen patients (mean age 43 +/- 7 years, 10 men) had low likelihood of coronary artery disease (CAD). All PET images were scored by consensus of two blinded readers on a standard 5-point scale using a 17-segment left ventricular model. A normal PET test was defined as a summed stress score of less than four. Obstructive CAD at coronary angiography was used as the gold-standard and was defined as luminal stenoses > or =50% in one or more major coronary arteries. The prevalence of obstructive disease at coronary angiography was 68% (39/57). The mean summed stress score was 12 +/- 12 for PGC images and was 18 +/- 14 for non-PGC images. Sensitivity and specificity for obstructive CAD were 90% (95% CI 88-99) and 72% (95% CI 52-93) for PGC images and 95% (95% CI 88-100) and 22% (95% CI 3-41) for non-PGC images. CONCLUSION: PGC in Rb-82 3D PET improves the specificity for obstructive CAD at coronary angiography with no significant loss in sensitivity.