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Context. Methyl isocyanide (CH3NC) is the isocyanide with the largest number of atoms confirmed in the interstellar medium (ISM), but it is not an abundant molecule, having only been detected towards a handful of objects. Conversely, its isomer, methyl cyanide (CH3CN), is one of the most abundant complex organic molecules detected in the ISM, with detections in a variety of low- and high-mass sources. Aims. The aims of this work are to determine the abundances of methyl isocyanide in the solar-type protostellar binary IRAS 16293–2422 and to understand the stark abundance differences observed between methyl isocyanide and methyl cyanide in the ISM. Methods. We use Atacama Large Millimeter/submillimeter Array (ALMA) observations from the Protostellar Interferometric Line Survey (PILS) to search for methyl isocyanide and compare its abundance with that of its isomer methyl cyanide. We use a new line catalogue from the Cologne Database for Molecular Spectroscopy (CDMS) to identify methyl isocyanide lines. We also model the chemistry with an updated version of the three-phase chemical kinetics model MAGICKAL, presenting the first chemical modelling of methyl isocyanide to date. Results. We detect methyl isocyanide for the first time in a solar-type protostar, IRAS 16293–2422 B, and present upper limits for its companion protostar, IRAS 16293–2422 A. Methyl isocyanide is found to be at least 20 times more abundant in source B compared to source A, with a CH3CN/CH3NC abundance ratio of 200 in IRAS 16293–2422 B and >5517 in IRAS 16293–2422 A. We also present the results of a chemical model of methyl isocyanide chemistry in both sources, and discuss the implications for methyl isocyanide formation mechanisms and the relative evolutionary stages of both sources. The chemical modelling is unable to match the observed CH3CN/CH3NC abundance ratio towards the B source at densities representative of that source. The modelling, however, is consistent with the upper limits for the A source. There are many uncertainties in the formation and destruction pathways of methyl isocyanide, and it is therefore not surprising that the initial modelling attempts do not reproduce observations. In particular, it is clear that some destruction mechanism of methyl isocyanide that does not destroy methyl cyanide is needed. Furthermore, these initial model results suggest that the final density plays a key role in setting the abundance ratio. The next steps are therefore to obtain further detections of methyl isocyanide in more objects, as well as undertaking more detailed physico-chemical modelling of sources such as IRAS16293. [ABSTRACT FROM AUTHOR]

Background and Aims: Increasing data suggest that stress-related neural activity (SNA) is associated with subsequent major adverse cardiovascular events (MACE) and may represent a therapeutic target. Current evidence is exclusively based on populations from the U.S. and Asia where limited information about cardiovascular disease risk was available. This study sought to investigate whether SNA imaging has clinical value in a well-characterized cohort of cardiovascular patients in Europe., Methods: In this single-centre study, a total of 963 patients (mean age 58.4 ± 16.1 years, 40.7% female) with known cardiovascular status, ranging from 'at-risk' to manifest disease, and without active cancer underwent 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography between 1 January 2005 and 31 August 2019. Stress-related neural activity was assessed with validated methods and relations between SNA and MACE (non-fatal stroke, non-fatal myocardial infarction, coronary revascularization, and cardiovascular death) or all-cause mortality by time-to-event analysis., Results: Over a maximum follow-up of 17 years, 118 individuals (12.3%) experienced MACE, and 270 (28.0%) died. In univariate analyses, SNA significantly correlated with an increased risk of MACE (sub-distribution hazard ratio 1.52, 95% CI 1.05-2.19; P = .026) or death (hazard ratio 2.49, 95% CI 1.96-3.17; P < .001). In multivariable analyses, the association between SNA imaging and MACE was lost when details of the cardiovascular status were added to the models. Conversely, the relationship between SNA imaging and all-cause mortality persisted after multivariable adjustments., Conclusions: In a European patient cohort where cardiovascular status is known, SNA imaging is a robust and independent predictor of all-cause mortality, but its prognostic value for MACE is less evident. Further studies should define specific patient populations that might profit from SNA imaging., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

The EOS™2D/3D system is a low-dose, 3D imaging system that utilizes two perpendicular X-ray beams to create simultaneous frontal and lateral images of the body. This is a useful modality to assess spinal pathologies. However, due to the slow imaging acquisition time up to 25 s, motion artifacts (MA) frequently occur. These artifacts may not be distinguishable from pathological findings, such as scoliosis, and may impair the diagnostic process. The aim of this study was to design a method to detect MA in EOS X-ray. We retrospectively analyzed EOS imaging from 40 patients wearing a radiopaque reference device during imaging. We drew a straight vertical line along the reference device. We measured deviations from it to quantify MA, presenting these findings through descriptive statistics. For a subset of patients with high MA, acquisitions were repeated after giving specific instructions to stand still. For these patients, we compared MA between the two acquisitions. In our study, a substantial proportion of patients exhibited MA ≥ 1 mm, with 80% in frontal projections and 87.9% in lateral projections. In the subjects who received a second acquisition, MA was significantly lower in the second images. Our method allows for a precise detection of MA on EOS images through a simple, yet reliable solution. Our method may improve the reliability of spine measurements, and reduce the risk of wrong diagnosis due to low imaging quality., (© 2024. The Author(s).)

Interbody cages are routinely used in lumbar reconstruction surgery of deformity cases for restoration of lordosis and sagittal balance of the spine. However, if hyperlordotic implants are inserted into the intervertebral space, special consideration has to be taken concerning the height of the neural foramen during cage implantation. The greater the lordotic angle of the cage is, the higher the posterior size of the cage needs to be in order to avoid neuroforaminal nerve root impingement. In this technical communication, we propose and clinically validate a stepwise mathematic model to predict neuroforaminal height in patients undergoing lumbar reconstruction with hyperlordotic cages. The length of the superior and inferior vertebral end plates including the height of the neural foramen are measured before implantation of the cage in standing sagittal view x-rays. By assumption of an isosceles triangle in combination with the posterior height and the lordotic angle of the cage, the neuroforaminal height after cage implantation can be estimated. By comparison of the predicted neuroforaminal height with age and sex dependent reference values, nerve root impingement can be avoided by selection of the necessary posterior height of the hyperlordotic cage while still gaining sufficient lumbar lordosis., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Posttraumatic spinal cord tethering and syringomyelia frequently lead to progressive neurological loss. Although several studies demonstrated favourable outcome following spinal cord detethering with/without shunting, additional research is required as no clear consensus exists over the ideal treatment strategy and knowledge about prognostic demographic determinants is currently limited. In this investigation, we retrospectively investigated 67 patients (56 men, 11 women) who were surgically treated and followed for symptomatic spinal cord tethering and syringomyelia from 2012 to 2022 at our center. Age (B-coefficient 0.396) and severity of trauma to the spinal cord (B-coefficient - 0.462) have been identified as independent predictors for the rate of development of symptomatic spinal cord tethering and syringomyelia (p < 0.001). Following untethering surgery including expansion duraplasty with/without shunting, 65.9% of patients demonstrated an improvement of neurological loss (p < 0.001) whereas 50.0% of patients displayed amelioration of spasticity and/or neuropathic pain (p < 0.001). Conclusively, active screening for symptomatic spinal cord tethering and syringomyelia, particularly in younger patients with severe spinal trauma, is crucial as surgical untethering with/without shunting is able to achieve favourable clinical outcomes. This knowledge may enable clinicians to tailor treatment strategies in spinal cord injury patients suffering from progressive neurological loss towards a more optimal and personalized patient care., (© 2023. The Author(s).)

Spinal cord injury (SCI) leads to compromised biomechanical stability due to impaired neuroprotection. This may trigger deformity and destruction of multiple segments of the spine which is known as spinal neuroarthropathy (SNA) or Charcot arthropathy. Surgical treatment of SNA is highly demanding in terms of reconstruction, realignment, and stabilization. In particular, construct failure due to the combination of high shear forces and reduced bone mineral density in the lumbosacral transition zone is a frequent complication in SNA. Notably, up to 75% of SNA patients need multiple revisions within the first year after surgery in order to achieve successful bony fusion. The purpose of this technical report is to present a novel surgical approach with higher overall construct stability to efficiently treat SNA and avoiding repetitive revisions. The new technique of triple rod stabilisation of the lumbosacral transition zone in combination with the introduction of tricortical laminovertebral (TLV) screws is demonstrated in three patients with complete SCI of the thoracic spinal cord. After surgery all patients reported an improvement of the Spinal Cord Independence Measure III (SCIM III) and none of the reported cases showed construct failure within an at least 9 months follow up period. Although TLV screws violate the integrity of the spinal canal, there were no complications with regard to cerebral spinal fluid fistulas and/or arachnopathies so far. The new concept of triple rod stabilization in combination with TLV screws provides improved construct stability in patients with SNA and thus could help to reduce revision and complications rates and improve patient outcome in this disabling degenerative disease., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jss.amegroups.com/article/view/10.21037/jss-22-103/coif). The authors have no conflicts of interest to declare., (2023 Journal of Spine Surgery. All rights reserved.)

Aims: Perivascular fat attenuation index (FAI) has emerged as a novel coronary computed tomography angiography (CCTA)-based biomarker predicting cardiovascular outcomes by capturing early coronary inflammation. It is currently unknown whether FAI adds prognostic value beyond that provided by single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI) and CCTA findings including coronary artery calcium scoring (CACS)., Methods and Results: A total of 492 patients (mean age 62.5 ± 10.8 years) underwent clinically indicated multimodality CCTA and electrocardiography (ECG)-gated 99m Tc-tetrofosmin SPECT-MPI between May 2005 and December 2008 at our institution, and follow-up data on major adverse cardiovascular events (MACE) was obtained for 314 patients. FAI was obtained from CCTA images and was measured around the right coronary artery (FAI[RCA]), the left anterior descending artery (FAI[LAD]), and the left main coronary artery (FAI[LMCA]). During a median follow-up of 2.7 years, FAI[RCA] > - 70.1 was associated with an increased rate of MACE (log rank p = 0.049), while no such association was seen for FAI[LAD] or FAI[LMCA] (p = NS). A multivariate Cox regression model accounting for cardiovascular risk factors, CCTA and SPECT-MPI findings identified FAI[RCA] as an independent predictor of MACE (HR 2.733, 95% CI: 1.220-6.123, p = 0.015). However, FAI[RCA] was no longer a significant predictor of MACE after adding CACS (p = 0.279). A first-order interaction term consisting of sex and FAI[RCA] was significant in both models (HR 2.119, 95% CI: 1.218-3.686, p = 0.008; and HR 2.071, 95% CI: 1.111-3.861, p = 0.022)., Conclusion: FAI does not add incremental prognostic value beyond multimodality MPI/CCTA findings including CACS. The diagnostic value of FAI[RCA] is significantly biased by sex.

Purpose: Amygdalar metabolic activity was shown to independently predict cardiovascular outcomes. However, little is known about age- and sex-dependent variability in neuronal stress responses among individuals free of cardiac disease. This study sought to assess age- and sex-specific differences of resting amygdalar metabolic activity in the absence of clinical cardiovascular disease., Methods: Amygdalar metabolic activity was assessed in 563 patients who underwent multimodality imaging by 18 F-fluorodeoxyglucose ( 18 F-FDG) positron emission tomography/computed tomography and echocardiography for the evaluation of cardiac function., Results: After exclusion of 294 patients with structural or functional cardiovascular pathologies, 269 patients (128 women) remained in the final population. 18 F-FDG amygdalar activity significantly decreased with age in men (r = - 0.278, P = 0.001), but not in women (r = 0.002, P = 0.983). Similarly, dichotomous analysis confirmed a lower amygdalar activity in men ≥ 50 years as compared to those < 50 years of age (0.79 ± 0.1 vs. 0.84 ± 0.1, P = 0.007), which was not observed in women (0.81 ± 0.1 vs. 0.82 ± 0.1, P = 0.549). Accordingly, a fully adjusted linear regression analysis identified age as an independent predictor of amygdalar activity only in men (B-coefficient - 0.278, P = 0.001)., Conclusion: Amygdalar activity decreases with age in men, but not in women. The use of amygdalar activity for cardiovascular risk stratification merits consideration of inherent age- and sex-dependent variability.

Background: Recent studies indicate that enhanced neuronal stress responses are associated with adverse cardiovascular outcomes. A chronic inflammatory state seems to mediate this detrimental neuro-cardiac communication. Statins are among the most widely prescribed medications in primary and secondary cardiovascular disease (CVD) prevention and not only lower lipid levels but also exhibit strong anti-inflammatory and neuroprotective effects. We therefore sought to investigate the influence of statins on neuronal stress responses in a patient cohort at risk for CVD., Methods: 563 patients (61.5 ± 14.0 years) who underwent echocardiography and 18 F-fluorodeoxyglucose ( 18 F-FDG) positron emission tomography (PET) were retrospectively identified. Metabolic activity of the amygdala, a part of the brain's salience network, was quantified by 18 F-FDG uptake, while normal cardiac morphology and function were assured by echocardiography. Vertebral bone marrow metabolism, a marker of inflammatory activity, was measured by 18 F-FDG PET., Results: Increased neuronal stress responses were associated with an increased inflammatory activity in the bone marrow (r = 0.152, p = 0.015) as well as with a subclinical reduction in left ventricular ejection fraction (LVEF, r = -0.138, p = 0.025). In a fully-adjusted linear regression model, statin treatment was identified as an independent, negative predictor of amygdalar metabolic activity (B-coefficient -0.171, p = 0.043)., Conclusions: Our hypothesis-generating investigation suggests a potential link between the anti-inflammatory actions of statins and reduced neuronal stress responses which could lead to improved cardiovascular outcomes. The latter warrants further studies in a larger and prospective population.

Cardiovascular disease (CVD) is the leading cause of death worldwide with mortality rates in women currently exceeding those in men. To date, evidence is widely lacking for unique female determinants of CVD. However, strong associations with psychological stress, obesity or elevated inflammatory biomarkers with adverse cardiovascular outcomes in women have been identified in various studies. Interestingly, amygdalar metabolic activity, a central neural structure involved in emotional stress processing, has proven to be an independent predictor of major adverse cardiovascular events (MACE). Moreover, upregulated amygdalar metabolism was directly linked to myocardial injury in women, but not in men. This newly suggested sex-dependent brain-heart interrelation was further supported by the discovery that bone marrow activity, a surrogate parameter of inflammation, represents a potential bridging link between amygdalar activity and cardiovascular pathology by fueling inflammatory processes that promote atherosclerotic disease. Such malignant cascade of events might account, at least in part, for the excess female mortality seen in women with coronary artery disease and calls for sex-specific research toward pharmacologic or behavioral modulators to improve cardiovascular outcomes, particularly in women. This mini review summarizes recent advances in cardiovascular sex-specific medicine, thereby focusing on the interplay between the limbic system, autonomic regulation and inflammatory biomarkers, which may help to tailor CVD management toward the female cardiovascular phenotype., Competing Interests: All authors have the following to disclose: The University Hospital of Zurich holds a research contract with GE Healthcare. CG has received research grants from the Novartis Foundation and speaker’s fees from Sanofi Genzyme, Switzerland., (Copyright © 2020 Gebhard, Bengs, Haider and Fiechter.)

Background: Recently, a new disease phenotype characterized by supra-normal left ventricular ejection fraction (snLVEF) has been suggested, based on large datasets demonstrating an increased all-cause mortality in individuals with an LVEF > 65%. The underlying mechanisms of this association are currently unknown., Methods: A total of 1367 patients (352 women, mean age 63.1 ± 11.6 years) underwent clinically indicated rest/adenosine stress ECG-gated 13 N-ammonia positron emission tomography (PET) between 1995 and 2017 at our institution. All patients were categorized according to LVEF. A subcohort of 698 patients (150 women) were followed for major adverse cardiac events (MACEs), a composite of cardiac death, non-fatal myocardial infarction, cardiac-related hospitalization, and revascularization., Results: The prevalence of a snLVEF (≥ 65%) was higher in women as compared to that in men (31.3% vs 18.8%, p < 0.001). In women, a significant reduction in coronary flow reserve (CFR, p < 0.001 vs normal LVEF) and a blunted heart rate reserve (% HRR, p = 0.004 vs normal LVEF) during pharmacological stress testing-a surrogate marker for autonomic dysregulation-were associated with snLVEF. Accordingly, reduced CFR and HRR were identified as strong and independent predictors for snLVEF in women in a fully adjusted multinomial regression analysis. After a median follow-up time of 5.6 years, women with snLVEF experienced more often a MACE than women with normal (55-65%) LVEF (log rank p < 0.001), while such correlation was absent in men (log rank p = 0.76)., Conclusion: snLVEF is associated with an increased risk of MACE in women, but not in men. Microvascular dysfunction and an increased sympathetic tone in women may account for this association.

Objective: Positron emission tomography/computed tomography with 18 F-fluorodeoxy-glucose ( 18 F-FDG-PET/CT) has become the standard staging modality in various tumor entities. Cancer patients frequently receive cardio-toxic therapies. However, routine cardiovascular assessment in oncologic patients is not performed in current clinical practice. Accordingly, this study sought to assess whether myocardial 18 F-FDG uptake patterns of patients undergoing oncologic PET/CT can be used for cardiovascular risk stratification., Methods: Myocardial 18 F-FDG uptake pattern was assessed in 302 patients undergoing both oncologic whole-body 18 F-FDG-PET/CT and myocardial perfusion imaging by single-photon emission computed tomography (SPECT-MPI) within a six-month period. Primary outcomes were myocardial 18 F-FDG uptake pattern, impaired myocardial perfusion, ongoing ischemia, myocardial scar, and left ventricular ejection fraction., Results: Among all patients, 109 (36.1%) displayed no myocardial 18 F-FDG uptake, 77 (25.5%) showed diffuse myocardial 18 F-FDG uptake, 24 (7.9%) showed focal 18 F-FDG uptake, and 92 (30.5%) had a focal on diffuse myocardial 18 F-FDG uptake pattern. In contrast to the other uptake patterns, focal myocardial 18 F-FDG uptake was predominantly observed in patients with myocardial abnormalities (i.e., abnormal perfusion, impaired LVEF, myocardial ischemia, or scar). Accordingly, a multivariate logistic regression identified focal myocardial 18 F-FDG uptake as a strong predictor of abnormal myocardial function/perfusion (odds ratio (OR) 5.32, 95% confidence interval (CI) 1.73-16.34, p = 0.003). Similarly, focal myocardial 18 F-FDG uptake was an independent predictor of ongoing ischemia and myocardial scar (OR 4.17, 95% CI 1.53-11.4, p = 0.005 and OR 3.78, 95% CI 1.47-9.69, p = 0.006, respectively)., Conclusions: Focal myocardial 18 F-FDG uptake seen on oncologic PET/CT indicates a significantly increased risk for multiple myocardial abnormalities. Obtaining and taking this information into account will help to stratify patients according to risk and will reduce unnecessary cardiovascular complications in cancer patients.

Purpose: Evidence to date has failed to reveal unique female determinants of cardiovascular disease. However, a strong association was recently observed between increased metabolic activity in the amygdala, a neural centre involved in the processing of emotions, and impaired myocardial function in women, but not in men. Given the stronger immune responses in females, we sought to retrospectively investigate the interaction between inflammation, perceived stress, and myocardial injury., Methods: Overall, 294 patients (mean age 66.9 ± 10.0 years, 28.6% women) underwent both, 99m Tc-tetrofosmin single-photon emission computed tomography myocardial perfusion imaging and 18 F-fluorodeoxyglucose ( 18 F-FDG) positron emission tomography/computed tomography for the assessment of cardiac function, bone marrow metabolism (surrogate marker of inflammation), and resting amygdalar activity., Results: A positive association was found between amygdalar metabolism and 18 F-FDG bone marrow uptake in women (r = 0.238, p = 0.029), but not in men (r = 0.060, p = 0.385). Linear regression models selected both, abnormal left ventricular ejection fraction (LVEF) and abnormal myocardial perfusion, as significant indicators of an increased amygdalar activity in women (B-coefficient LVEF, - 0.096; p = 0.021; abnormal myocardial perfusion, 3.227; p = 0.043), but not in men (bone marrow p = 0.076; abnormal myocardial perfusion p = 0.420). Accordingly, an interaction term consisting of sex and LVEF/abnormal myocardial perfusion was significant (p = 0.043 and p = 0.015, respectively)., Conclusions: Upregulated amygdalar metabolism is associated with an enhanced inflammatory state in female patients with impaired cardiac function. Given that enhanced activity of the limbic system is associated with worse cardiovascular outcomes, our study suggests that a focus on inflammatory markers and indicators of distress might help to tailor cardiovascular risk assessment and therapy towards the female cardiovascular phenotype.

Background: Sexual dimorphism in the manifestation of coronary artery disease (CAD) has unleashed a call to reconsider cardiovascular risk assessment. Alterations of bone mineral density (BMD) have been associated with congestive heart failure and appear to be modified by sex. However, the sex-specific association between BMD, myocardial perfusion, and cardiovascular outcomes is currently unknown., Methods: A total number of 491 patients (65.9 ± 10.7 years, 32.4% women) underwent 13 N-ammonia positron emission tomography/computed tomography for evaluation of CAD, and were tracked for major adverse cardiac events (MACEs)., Results: Event-free survival (median follow-up time of 4.3 ± 2.0 years) was significantly reduced in patients with low (≤ 100 Hounsfield units) compared to those with higher BMD (log-rank P = .037). Accordingly, reduced BMD was chosen as significant predictor of MACE in a fully adjusted proportional hazards regression model (P = .015). Further, a first-order interaction term consisting of sex and BMD was statistically significant (P = .007). BMD was significantly lower in patients with abnormal myocardial perfusion or impaired left ventricular ejection fraction (P < .05). This difference, however, was noticed in men, but not in women., Conclusions: The association between low BMD and cardiovascular disease is sex dependent. Our data suggest that quantification of BMD during myocardial perfusion imaging for evaluation of CAD may be particularly useful in men.

Background: Incomplete ossification of the pars interarticularis will result in a pars defect, a common cause of low back pain in youth and strongly associated with participation in high-impact sports. If left untreated, it can result in spondylolisthesis, causing dynamic canal stenosis, low back pain, and radiculopathy. The treatment of pars defect was first described by Bucks in 1970, who used screws in the lamina placed through an upward and outward direction. However, because of the multiple inclusion and exclusion criteria and narrow margin of error, the Bucks pars repair technique is not commonly performed., Methods: A 28-year-old woman had with low back pain that she had been experiencing since mid-adolescence. Computed tomography revealed a bilateral L5 pars defect without spondylolisthesis. Her L5 vertebra was reconstructed virtually. The screw trajectories, a 3-dimensional (3D) model of the vertebra, and a patient-specific drill guide (PSDG) were designed and printed using positioning guide software (MySpine MC Guides [Medacta International SA, Castel San Petro, Switzerland]). A modified Bucks procedure using cannulated compression screws and the PSDG was performed., Results: Follow-up computed tomography revealed accurate placement of the compression screws, mirroring the planned trajectory. The patient was pain free at 3 months postoperatively, and early union across the defect was visualized on the 5-month radiographic imaging study., Conclusion: Using 3D planning software, complex surgical procedures can be planned using the patient's anatomy and computed tomography. With the aid of 3D-printed PSDGs, screw placement in narrow corridors, such as was shown in our case, is safe, efficient, and achievable., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background Increasing evidence suggests a psychosomatic link between neural systems and the heart. In light of the growing burden of ischemic cardiovascular disease across the globe, a better understanding of heart-brain interactions and their implications for cardiovascular treatment strategies is needed. Thus, we sought to investigate the interaction between myocardial injury and metabolic alterations in central neural areas in patients with suspected or known coronary artery disease. Methods and Results The association between resting metabolic activity in distinct neural structures and cardiac function was analyzed in 302 patients (aged 66.8±10.2 years; 70.9% men) undergoing fluor-18-deoxyglucose positron emission tomography and 99m Tc-tetrofosmin single-photon emission computed tomography myocardial perfusion imaging. There was evidence for reduction of callosal, caudate, and brainstem fluor-18-deoxyglucose uptake in patients with impaired left ventricular ejection fraction (<55% versus ≥55%: P =0.047, P =0.022, and P =0.013, respectively) and/or in the presence of myocardial ischemia (versus normal perfusion: P =0.010, P =0.013, and P =0.016, respectively). In a sex-stratified analysis, these differences were observed in men, but not in women. A first-order interaction term consisting of sex and impaired left ventricular ejection fraction or myocardial ischemia was identified as predictor of metabolic activity in these neural regions (left ventricular ejection fraction: P =0.015 for brainstem; myocardial ischemia: P =0.004, P =0.018, and P =0.003 for callosal, caudate, or brainstem metabolism, respectively). Conclusions Myocardial dysfunction and injury are associated with reduced resting metabolic activity of central neural structures, including the corpus callosum, the caudate nucleus, and the brainstem. These associations differ in women and men, suggesting sex differences in the pathophysiological interplay of the nervous and cardiovascular systems.

Background: Left ventricular (LV) ejection fraction (EF) during high dobutamine stress (HD) by real-time gated-SPECT myocardial perfusion imaging (MPI) on a cadmium-zinc-telluride (CZT) gamma camera was validated versus cardiac magnetic resonance imaging (CMR)., Methods and Results: After injecting 99mTc-tetrofosmin (320 MBq) in 50 patients (mean age 64 +/- 11 years), EF at rest and post-stress as well as relevant changes in EF at HD (ΔEF ≥ 5%) were assessed. CZT and CMR rest EF values yielded an excellent correlation and agreement (r = 0.96; P < 0.001; Bland-Altman limits of agreement (BA): + 0 to 14.8%). HD EF acquisition was feasible using CZT and correlated better to HD CMR EF than did post-stress CZT EF (r = 0.85 vs 0.76, respectively, all P < 0.001). Agreement in ΔEF detection between HD CMR and immediate post-stress CZT (reflecting standard acquisition using conventional SPECT camera unable to scan during stress) was 45%, while this increased to 85% with real-time HD CZT scan., Conclusion: Real-time ultrafast dobutamine gated-SPECT MPI with a CZT device is feasible and provides accurate measurements of HD LV performance.

Aim: Amongst patients with coronary artery disease (CAD), women experience relatively worse outcomes as compared to men. Evidence to date has failed to explore unique female imaging targets as major determinants of cardiovascular risk. We sought to assess the prognostic value of epicardial (EFV) and intrathoracic fat volume (IFV) quantification in women and men with suspected and known CAD., Methods and Results: Intrathoracic fat volume and EFV were calculated from non-contrast CT and analyzed in a propensity-matched cohort of 190 patients (95 women, mean age 62.5 ± 11.3 years) undergoing myocardial perfusion imaging (MPI) and coronary computed tomography angiography (CCTA) for evaluation of CAD. IFV and EFV were significantly lower in women as compared to men (198.2 ± 78.4 vs 293.2 ± 114.7 cm 3 and 105.6 ± 48.9 vs 135.8 ± 60.9 cm 3 , p < 0.001) and showed a strong association with coronary artery calcium score (CACS) and obstructive CAD in women (p < 0.05), but not in men. Fat volumes were not related to abnormal MPI in either population (p = NS). During a median follow-up of 2.8 years, high IFV was associated with reduced event free survival (log rank = 0.019 vs low IFV) in women, but not in men. Accordingly, a multivariate Cox regression model adjusted for cardiovascular risk factors, CACS, CCTA, and MPI findings selected IFV as a significant predictor of major adverse cardiovascular events (MACE) in women (HR 1.32, 95%CI 1.18-1.55, p = 0.001)., Conclusion: Quantification of IFV provides incremental prognostic value for MACE in women, beyond that provided by traditional risk factors and imaging findings., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Although women with cardiovascular disease experience relatively worse outcomes as compared to men, substantial knowledge gaps remain regarding the unique female determinants of cardiovascular risk. Heart rate (HR) responses to vasodilator stress mirror autonomic activity and may carry important long-term prognostic information in women., Methods and Results: Hemodynamic changes during adenosine stress were recorded in a total of 508 consecutive patients (104 women) undergoing clinically indicated 13 N-ammonia Positron-Emission-Tomography (PET) at our institution. Following propensity matching, 202 patients (101 women, mean age 61.3 ± 12.6 years) were analyzed. During a median follow-up of 5.6 years, 97 patients had at least one cardiac event, including 17 cardiac deaths. Heart rate reserve (% HRR) during adenosine infusion was significantly higher in women as compared to men (23.8 ± 19.5 vs 17.3 ± 15.3, p = 0.009). A strong association between 10-year cardiovascular endpoints and a blunted HRR was observed in women, while this association was less pronounced in men. Accordingly, in women, but not in men, reduced HRR was selected as a strong predictor for adverse cardiovascular events in a Cox regression model fully adjusted for imaging findings and traditional risk factors (HR 2.41, 95% CI 1.23-4.75, p = 0.011). Receiver operating characteristics (ROC) curves revealed that a blunted HRR <21% was a powerful predictor for MACE in women with a sensitivity of 77% and a specificity of 68%., Conclusion: Blunted HRR to adenosine stress adds incremental prognostic value for long-term cardiovascular outcomes in women beyond that provided by traditional risk factors and imaging findings.

Background:  Inflammation plays a fundamental role in mediating all stages of atherosclerosis. Given the higher prevalence of inflammatory rheumatologic conditions in women and the female propensity towards worse cardiovascular outcomes, refined strategies are needed to better identify the high-risk female cardiovascular phenotype., Objectives:  This article aims to assess sex-specific links between inflammatory processes and the development and progression of ischemic heart disease., Patients and Methods:  The relationship between vertebral bone marrow metabolism-a marker of inflammation-and myocardial injury was retrospectively assessed in 294 patients (28.6% women, mean age: 66.9 ± 10.0 years) who underwent 18 F-fluorodeoxyglucose ( 18 F-FDG) positron emission tomography (PET) and 99m Tc-tetrofosmin single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI)., Results:  A significant increase in 18 F-FDG bone marrow uptake was observed in women with impaired myocardial perfusion (SPECT-MPI) as compared to women with normal myocardial perfusion (standardized uptake value [SUV]: 2.2 ± 1.2 vs. 1.7 ± 0.5, p  = 0.013), while no such difference was observed in men (SUV: 1.6 ± 0.8 vs. 1.6 ± 0.4, p  = 0.372). Furthermore, a significant inverse correlation between left ventricular ejection fraction (LVEF) and bone marrow metabolism was seen in women ( r  = -0.229, p  = 0.037), but not in men ( r  = -0.075, p  = 0.289). Accordingly, in women, but not in men, bone marrow activity was identified as an independent predictor of both, reduced LVEF ( β -coefficient, -4.537; p  = 0.040) and impaired myocardial perfusion (β-coefficient, 0.138; p  = 0.014)., Conclusion:  A strong link between bone marrow metabolism and impaired myocardial function and perfusion was observed in women, but not in men. Our data suggest that novel biomarkers of inflammation might help to identify women at risk for ischemic cardiomyopathy and to tailor disease management to the female cardiovascular phenotype., Competing Interests: All authors have the following to disclose: The University Hospital of Zurich holds a research contract with GE Healthcare. C.G. has received research grants from the Novartis Foundation, Switzerland., (Georg Thieme Verlag KG Stuttgart · New York.)