Sex differences in the SOFA score of ICU patients with sepsis or septic shock: a nationwide analysis.

BACKGROUND: The Sequential Organ Failure Assessment (SOFA) score is an important tool in diagnosing sepsis and quantifying organ dysfunction. However, despite emerging evidence of differences in sepsis pathophysiology between women and men, sex is currently not being considered in the SOFA score. We aimed to investigate potential sex-specific differences in organ dysfunction, as measured by the SOFA score, in patients with sepsis or septic shock and explore outcome associations. METHODS: Retrospective analysis of sex-specific differences in the SOFA score of prospectively enrolled ICU patients with sepsis or septic shock admitted to one of 85 certified Swiss ICUs between 01/2021 and 12/2022. RESULTS: Of 125,782 patients, 5947 (5%) were admitted with a clinical diagnosis of sepsis (2244, 38%) or septic shock (3703, 62%). Of these, 5078 (37% women) were eligible for analysis. A statistically significant difference of the total SOFA score on admission was found between women (mean 7.5 ± SD 3.6 points) and men (7.8 ± 3.6 points, Wilcoxon rank-sum p < 0.001). This was driven by differences in the coagulation (p = 0.008), liver (p < 0.001) and renal (p < 0.001) SOFA components. Differences between sexes were more prominent in younger patients < 52 years of age (women 7.1 ± 4.0 points vs men 8.1 ± 4.2 points, p = 0.004). No sex-specific differences were found in ICU length of stay (women median 2.6 days (IQR 1.3-5.3) vs men 2.7 days (IQR 1.2-6.0), p = 0.13) and ICU mortality (women 14% vs men 15%, p = 0.17). CONCLUSION: Sex-specific differences exist in the SOFA score of patients admitted to a Swiss ICU with sepsis or septic shock, particularly in laboratory-based components. Although the clinical meaningfulness of these differences is unclear, a reevaluation of sex-specific thresholds for SOFA score components is warranted in an attempt to make more accurate and individualised classifications.

Heart-brain axis: Pushing the boundaries of cardiovascular molecular imaging.

Despite decades of research, the heart-brain axis continues to challenge investigators seeking to unravel its complex pathobiology. Strong epidemiologic evidence supports a link by which insult or injury to one of the organs increases the risk of pathology in the other. The putative pathways have important differences between sexes and include alterations in autonomic function, metabolism, inflammation, and neurohormonal mechanisms that participate in crosstalk between the heart and brain and contribute to vascular changes, the development of shared risk factors, and oxidative stress. Recently, given its unique ability to characterize biological processes in multiple tissues simultaneously, molecular imaging has yielded important insights into the interplay of these organ systems under conditions of stress and disease. Yet, additional research is needed to probe further into the mechanisms underlying the heart-brain axis and to evaluate the impact of targeted interventions.

Imaging of the brain-heart axis: prognostic value in a European setting.

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.

Duration of adenosine-induced myocardial hyperemia - Insights from quantitative 13N-ammonia positron emission tomography myocardial perfusion imaging.

AIMS: To assess the impact of adenosine on quantitative myocardial blood flow (MBF) in a rapid stress-rest protocol compared to a rest-stress protocol using 13N-ammonia positron emission tomography (PET) myocardial perfusion imaging (MPI) and to gain insights into the time dependency of such effects. METHODS AND RESULTS: Quantitative MBF at rest (rMBF), during adenosine-induced stress (sMBF) and myocardial flow reserve (MFR) were obtained from 331 retrospectively identified patients who underwent 13N-ammonia PET-MPI for suspected chronic coronary syndrome and who all exhibited no perfusion defects. Of these, 146 (44.1%) underwent a rapid stress-rest protocol with a time interval (Δtstress-rest) of 20 ± 4 minutes between adenosine infusion offset and rest-imaging, as per clinical routine. The remaining 185 (55.9%) patients underwent a rest-stress protocol and served as the reference. Groups did not differ regarding demographics, risk factors, medication, left ventricular function, and calcium scores. rMBF was significantly higher in the stress-rest vs. the rest-stress group (0.80 [IQR 0.66-1.00] vs. 0.70 [0.58-0.83] ml·min-1·g-1, p < 0.001) and, as sMBF was identical between groups (2.52 [2.20-2.96] vs. 2.50 [1.96-3.11], p = 0.347), MFR was significantly lower in the stress-rest group (3.07 [2.43-3.88] vs. 3.50 [2.63-4.10], p < 0.001). There was a weak correlation between Δtstress-rest and rMBF (r = -0.259, p = 0.002) and between Δtstress-rest and MFR (r = 0.163, p = 0.049), and the proportion of patients with abnormally high rMBF was significantly decreasing with increasing Δtstress-rest. CONCLUSIONS: Intravenously applied adenosine induces a long-lasting hyperemic effect on the myocardium. Consequently, rapid stress-rest protocols could lead to an overestimation of rMBF and an underestimation of MFR.

Patterns of aortic valve replacement in Europe and adoption by sex.

OBJECTIVE: Management of patients with severe aortic stenosis (AS) may differ according to the patient sex. This study aimed to describe patterns of aortic valve replacement (AVR) for severe AS across Europe, including stratification by sex. METHODS: Procedure volume data for surgical aortic valve replacement (SAVR) and transcatheter aortic valve implantation (TAVI) for six years (2015-2020) were extracted from national databases for Austria, Czech Republic, Denmark, England, Finland, France, Germany, Norway, Poland, Spain, Sweden, and Switzerland and stratified by sex. Patients per million population (PPM) undergoing AVR per year were calculated using population estimates from Eurostat. RESULTS: Between 2015 and 2019, AVR procedures grew at an average annual rate of 3.9%. In 2020, the average total PPM undergoing AVR across all countries was 339, with 51% of procedures being TAVI and 49% SAVR. AVR PPM varied widely between countries, with the highest and lowest in Germany and Poland, respectively. The average total PPM was higher for men than women (423 vs. 258), but a higher proportion of women (62%) than men (44%) received TAVI. The proportion of TAVI among total AVR procedures increased with age, with an overall average of 96% of men and 98% of women aged ≥85 years receiving TAVI; however, adoption of TAVI varied by country. CONCLUSIONS: The analysis of temporal trends in the adoption of TAVI vs. SAVR across Europe showed significant variations. Despite the higher use of TAVI vs. SAVR in women, overall rates of AV intervention in women were lower compared to men.

Non-Invasive Assessment of Endothelial Shear Stress in Myocardial Bridges Using Coronary Computed Tomography Angiography.

Myocardial bridging (MB) is a segment of coronary arteries with an intramural course, typically spared from atherosclerosis, while the adjacent proximal segment is reported to be atherosclerosis-prone, a phenomenon contributed to local endothelial shear stress (ESS). We aimed to describe the ESS milieu in coronaries with MBs combining coronary computed tomography angiography with computational fluid dynamics and to investigate the association of atherosclerosis presence proximal to MBs with hemorheological characteristics. Patients (n = 36) were identified and 36 arteries with MBs (11 deep and 25 superficial) were analyzed. ESS did not fluctuate 5 mm proximally to MBs vs 5 mm within MBs (0.94 vs 1.06 Pa, p = .56). There was no difference when comparing ESS in the proximal versus mid versus distal MB segments (1.48 vs 1.37 vs 1.9 Pa, p = ns). In arteries with plaques (n = 12), no significant ESS variances were observed around the MB entrance, when analyzing all arteries (p = .81) and irrespective of morphological features of the bridged segment (deep MBs; p = .65, superficial MBs; p = .84). MBs are characterized by homogeneous, atheroprotective ESS, possibly explaining the absence of atherosclerosis within bridged segments. The interplay between ESS and atherosclerosis is potentially not different in arteries with MB compared with arteries without bridges.

COVID-19 vaccine-associated myocarditis: Analysis of the suspected cases reported to the EudraVigilance and a systematic review of the published literature.

Background: Myocarditis secondary to Coronavirus Disease 2019 (COVID-19) vaccination has been reported in the literature. Objective: This study aimed to characterize the reported cases of myocarditis after COVID-19 vaccination based on age, gender, doses, and vaccine type from published literature and the EudraVigilance database. Methods: We performed an analysis in the EudraVigilance database (until December 18, 2021) and a systematic review of published literature for reported cases of suspected myocarditis and pericarditis (until 30th June 2022) after the COVID-19 vaccination. Results: EudraVigilance database analysis revealed 16,514 reported cases of myocarditis or pericarditis due to the vaccination with COVID-19 vaccines. The cases of myo- or pericarditis were reported predominantly in the age group of 18-64 (n = 12,214), and in males with a male-to-female (M: F) ratio of 1.7:1. The mortality among myocarditis patients was low, with 128 deaths (2 cases per 10.000.000 administered doses) being reported. For the systematic review, 72 studies with 1026 cases of myocarditis due to the vaccination with COVID-19 vaccines were included. The analysis of published cases has revealed that the male gender was primarily affected with myocarditis post-COVID-vaccination. The median (IQR) age of the myocarditis cases was 24.6 [19.5-34.6] years, according to the systematic review of the literature. Myocarditis cases were most frequently published after the vaccination with m-RNA vaccines and after the second vaccination dose. The overall mortality of published cases was low (n = 5). Conclusion: Myocarditis is a rare serious adverse event associated with a COVID-19 vaccination. With early recognition and management, the prognosis of COVID-19 vaccine-induced myocarditis is favorable.

Patterns of Aortic Valve Replacement in Europe: Adoption by Age.

INTRODUCTION: The management of patients with severe aortic stenosis may differ according to patients' age. The aim of this analysis was to describe patterns of aortic valve replacement (AVR) use in European countries stratified by age. METHODS: Procedure volume data for AVR, including surgical aortic valve replacement (sAVR) and transcatheter aortic valve implantation (TAVI), for the years 2015-2020 were obtained from national databases for twelve European countries (Austria, the Czech Republic, Denmark, England, Finland, France, Germany, Norway, Poland, Spain, Sweden, and Switzerland). Procedure volumes were reported by patient age (<50 years, 5-year age groups between 50 and 85 years, and ≥85 years). Patients per million (PPM) population undergoing AVR each year were calculated using population estimates from Eurostat. RESULTS: AVR PPM varied widely between countries, from 508 PPM in Germany to 174 PPM in Poland in 2020. TAVI rates ranged from 61% in Switzerland and Finland to 25% in Poland. AVR PPM increased with age to a peak at 80-84 years, after which it decreased again. AVR procedures increased from 2015 to 2019 at an average annual rate of 3.9%. AVR increased more substantially in people aged ≥80 years than in younger age groups; these older age groups accounted for 30% of all AVR procedures in 2015 and 35% in 2019. TAVI accounted for an increasing proportion of all AVR procedures as patient age increased; an overall average of 96% of males and 98% of females aged ≥85 years received TAVI as the treatment modality, although adoption of TAVI differed between countries. CONCLUSIONS: There is considerable variation in the rates of AVR use and the adoption of TAVI versus sAVR between European countries. The use of TAVI has increased in recent years, particularly for older patients.

Tales from the future-nuclear cardio-oncology, from prediction to diagnosis and monitoring.

Cancer and cardiovascular diseases (CVD) often share common risk factors, and patients with CVD who develop cancer are at high risk of experiencing major adverse cardiovascular events. Additionally, cancer treatment can induce short- and long-term adverse cardiovascular events. Given the improvement in oncological patients' prognosis, the burden in this vulnerable population is slowly shifting towards increased cardiovascular mortality. Consequently, the field of cardio-oncology is steadily expanding, prompting the need for new markers to stratify and monitor the cardiovascular risk in oncological patients before, during, and after the completion of treatment. Advanced non-invasive cardiac imaging has raised great interest in the early detection of CVD and cardiotoxicity in oncological patients. Nuclear medicine has long been a pivotal exam to robustly assess and monitor the cardiac function of patients undergoing potentially cardiotoxic chemotherapies. In addition, recent radiotracers have shown great interest in the early detection of cancer-treatment-related cardiotoxicity. In this review, we summarize the current and emerging nuclear cardiology tools that can help identify cardiotoxicity and assess the cardiovascular risk in patients undergoing cancer treatments and discuss the specific role of nuclear cardiology alongside other non-invasive imaging techniques.

Spinal cord tethering and syringomyelia after trauma: impact of age and surgical outcome.

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.

Early menopause and cardiovascular risk factors: a cross-sectional and longitudinal study.

OBJECTIVE: The aim of the study is to evaluate the cross-sectional and longitudinal association of early natural menopause with changes in cardiovascular risk factors (CVRFs). METHODS: Postmenopausal women from the Swiss CoLaus study, reporting age at natural menopause (ANM) and having CVRFs measurements (blood lipids, blood pressure, glucose, homeostatic model assessment for insulin resistance [HOMA-IR], and inflammatory markers) at baseline (2003-2006) and first follow-up (2009-2012) were eligible for analysis. Age at natural menopause was analyzed as a continuous variable and in categories (ANM <45 and ≥45 y old). Linear regression analysis and linear mixed models were used to assess whether ANM is associated cross-sectionally and longitudinally with changes in CVRFs. Models were adjusted for demographic characteristics, lifestyle-related factors, time since menopause, medication, and clinical conditions. RESULTS: We analyzed 981 postmenopausal women. The cross-sectional analysis showed that women with ANM younger than 45 years had lower diastolic blood pressure (ß = -3.76 mm Hg; 95% confidence interval [CI] = -5.86 to -1.65) compared with women whose ANM was 45 years or older. In the longitudinal analysis, ANM younger than 45 years was associated with changes in log insulin (ß = 0.26; 95% CI = 0.08 to 0.45) and log homeostatic model assessment for insulin resistance levels (ß = 0.28; 95% CI = 0.08 to 0.48). No associations were found between ANM and other CVRFs. CONCLUSIONS: Early menopause may be associated with changes in glucose metabolism, while it may have little to no impact on other CVRFs. Larger longitudinal studies are needed to replicate our findings.

Long-Term Mortality after New-Onset Atrial Fibrillation in COVID-19.

Background: Atrial fibrillation (AF) has been described as a common cardiovascular manifestation in patients suffering from coronavirus disease 2019 (COVID-19) and has been suggested to be a potential risk factor for a poor clinical outcome. Methods: In this observational study, all patients hospitalized due to COVID-19 in 2020 in the Cantonal Hospital of Baden were included. We assessed clinical characteristics, in-hospital outcomes as well as long-term outcomes with a mean follow-up time of 278 (±90) days. Results: Amongst 646 patients diagnosed with COVID-19 (59% male, median age: 70 (IQR: 59-80)) in 2020, a total of 177 (27.4%) patients were transferred to the intermediate/intensive care unit (IMC/ICU), and 76 (11.8%) were invasively ventilated during their hospitalization. Ninety patients (13.9%) died. A total of 116 patients (18%) showed AF on admission of which 34 (29%) had new-onset AF. Patients with COVID-19 and newly diagnosed AF were more likely to require invasive ventilation (OR: 3.5; p = 0.01) but did not encounter an increased in-hospital mortality. Moreover, AF neither increased long-term mortality nor the number of rehospitalizations during follow-up after adjusting for confounders. Conclusions: In patients suffering from COVID-19, the new-onset of AF on admission was associated with an increased risk of invasive ventilation and transfer to the IMC/ICU but did not affect in-hospital or long-term mortality.

Translational molecular imaging and drug development in Parkinson's disease.

Parkinson's disease (PD) is a progressive neurodegenerative disorder that primarily affects elderly people and constitutes a major source of disability worldwide. Notably, the neuropathological hallmarks of PD include nigrostriatal loss and the formation of intracellular inclusion bodies containing misfolded α-synuclein protein aggregates. Cardinal motor symptoms, which include tremor, rigidity and bradykinesia, can effectively be managed with dopaminergic therapy for years following symptom onset. Nonetheless, patients ultimately develop symptoms that no longer fully respond to dopaminergic treatment. Attempts to discover disease-modifying agents have increasingly been supported by translational molecular imaging concepts, targeting the most prominent pathological hallmark of PD, α-synuclein accumulation, as well as other molecular pathways that contribute to the pathophysiology of PD. Indeed, molecular imaging modalities such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT) can be leveraged to study parkinsonism not only in animal models but also in living patients. For instance, mitochondrial dysfunction can be assessed with probes that target the mitochondrial complex I (MC-I), while nigrostriatal degeneration is typically evaluated with probes designed to non-invasively quantify dopaminergic nerve loss. In addition to dopaminergic imaging, serotonin transporter and N-methyl-D-aspartate (NMDA) receptor probes are increasingly used as research tools to better understand the complexity of neurotransmitter dysregulation in PD. Non-invasive quantification of neuroinflammatory processes is mainly conducted by targeting the translocator protein 18 kDa (TSPO) on activated microglia using established imaging agents. Despite the overwhelming involvement of the brain and brainstem, the pathophysiology of PD is not restricted to the central nervous system (CNS). In fact, PD also affects various peripheral organs such as the heart and gastrointestinal tract - primarily via autonomic dysfunction. As such, research into peripheral biomarkers has taken advantage of cardiac autonomic denervation in PD, allowing the differential diagnosis between PD and multiple system atrophy with probes that visualize sympathetic nerve terminals in the myocardium. Further, α-synuclein has recently gained attention as a potential peripheral biomarker in PD. This review discusses breakthrough discoveries that have led to the contemporary molecular concepts of PD pathophysiology and how they can be harnessed to develop effective imaging probes and therapeutic agents. Further, we will shed light on potential future trends, thereby focusing on potential novel diagnostic tracers and disease-modifying therapeutic interventions.

Temporal trends in mortality and provision of intensive care in younger women and men with acute myocardial infarction or stroke.

BACKGROUND: Timely management of acute myocardial infarction (AMI) and acute stroke has undergone impressive progress during the last decade. However, it is currently unknown whether both sexes have profited equally from improved strategies. We sought to analyze sex-specific temporal trends in intensive care unit (ICU) admission and mortality in younger patients presenting with AMI or stroke in Switzerland. METHODS: Retrospective analysis of temporal trends in 16,954 younger patients aged 18 to ≤ 52 years with AMI or acute stroke admitted to Swiss ICUs between 01/2008 and 12/2019. RESULTS: Over a period of 12 years, ICU admissions for AMI decreased more in women than in men (- 6.4% in women versus - 4.5% in men, p < 0.001), while ICU mortality for AMI significantly increased in women (OR 1.2 [1.10-1.30], p = 0.032), but remained unchanged in men (OR 0.99 [0.94-1.03], p = 0.71). In stroke patients, ICU admission rates increased between 3.6 and 4.1% per year in both sexes, while ICU mortality tended to decrease only in women (OR 0.91 [0.85-0.95, p = 0.057], but remained essentially unaltered in men (OR 0.99 [0.94-1.03], p = 0.75). Interventions aimed at restoring tissue perfusion were more often performed in men with AMI, while no sex difference was noted in neurovascular interventions. CONCLUSION: Sex and gender disparities in disease management and outcomes persist in the era of modern interventional neurology and cardiology with opposite trends observed in younger stroke and AMI patients admitted to intensive care. Although our study has several limitations, our data suggest that management and selection criteria for ICU admission, particularly in younger women with AMI, should be carefully reassessed.

Radiomics for the detection of diffusely impaired myocardial perfusion: A proof-of-concept study using 13N-ammonia positron emission tomography.

AIM: The current proof-of-concept study investigates the value of radiomic features from normal 13N-ammonia positron emission tomography (PET) myocardial retention images to identify patients with reduced global myocardial flow reserve (MFR). METHODS: Data from 100 patients with normal retention 13N-ammonia PET scans were divided into two groups, according to global MFR (i.e., < 2 and ≥ 2), as derived from quantitative PET analysis. We extracted radiomic features from retention images at each of five different gray-level (GL) discretization (8, 16, 32, 64, and 128 bins). Outcome independent and dependent feature selection and subsequent univariate and multivariate analyses was performed to identify image features predicting reduced global MFR. RESULTS: A total of 475 radiomic features were extracted per patient. Outcome independent and dependent feature selection resulted in a remainder of 35 features. Discretization at 16 bins (GL16) yielded the highest number of significant predictors of reduced MFR and was chosen for the final analysis. GLRLM_GLNU was the most robust parameter and at a cut-off of 948 yielded an accuracy, sensitivity, specificity, negative and positive predictive value of 67%, 74%, 58%, 64%, and 69%, respectively, to detect diffusely impaired myocardial perfusion. CONCLUSION: A single radiomic feature (GLRLM_GLNU) extracted from visually normal 13N-ammonia PET retention images independently predicts reduced global MFR with moderate accuracy. This concept could potentially be applied to other myocardial perfusion imaging modalities based purely on relative distribution patterns to allow for better detection of diffuse disease.

Rest/stress myocardial perfusion imaging by positron emission tomography with 18F-Flurpiridaz: A feasibility study in mice.

BACKGROUND: Myocardial perfusion imaging by positron emission tomography (PET-MPI) is the current gold standard for quantification of myocardial blood flow. 18F-flurpiridaz was recently introduced as a valid alternative to currently used PET-MPI probes. Nonetheless, optimum scan duration and time interval for image analysis are currently unknown. Further, it is unclear whether rest/stress PET-MPI with 18F-flurpiridaz is feasible in mice. METHODS: Rest/stress PET-MPI was performed with 18F-flurpiridaz (0.6-3.0 MBq) in 27 mice aged 7-8 months. Regadenoson (0.1 µg/g) was used for induction of vasodilator stress. Kinetic modeling was performed using a metabolite-corrected arterial input function. Image-derived myocardial 18F-flurpiridaz uptake was assessed for different time intervals by placing a volume of interest in the left ventricular myocardium. RESULTS: Tracer kinetics were best described by a two-tissue compartment model. K1 ranged from 6.7 to 20.0 mL·cm-3·min-1, while myocardial volumes of distribution (VT) were between 34.6 and 83.6 mL·cm-3. Of note, myocardial 18F-flurpiridaz uptake (%ID/g) was significantly correlated with K1 at rest and following pharmacological vasodilation for all time intervals assessed. However, while Spearman's coefficients (rs) ranged between 0.478 and 0.681, R2 values were generally low. In contrast, an excellent correlation of myocardial 18F-flurpiridaz uptake with VT was obtained, particularly when employing the averaged myocardial uptake from 20 to 40 min post tracer injection (R2 ≥ 0.98). Notably, K1 and VT were similarly sensitive to pharmacological vasodilation induction. Further, mean stress-to-rest ratios of K1, VT, and %ID/g 18F-flurpiridaz were virtually identical, suggesting that %ID/g 18F-flurpiridaz can be used to estimate coronary flow reserve (CFR) in mice. CONCLUSION: Our findings suggest that a simplified assessment of relative myocardial perfusion and CFR, based on image-derived tracer uptake, is feasible with 18F-flurpiridaz in mice, enabling high-throughput mechanistic CFR studies in rodents.

Left ventricular function and volumes from gated [13N]-ammonia positron emission tomography myocardial perfusion imaging: A prospective head-to-head comparison against CMR using a hybrid PET/MR device.

BACKGROUND: Positron emission tomography (PET) myocardial perfusion imaging (MPI) can be used to evaluate left ventricular (LV) volumes and function. We performed a head-to-head comparison of LV function and volumes obtained simultaneously using [13N]-ammonia-PET and cardiac magnetic resonance (CMR), with the latter serving as the reference standard. METHODS AND RESULTS: In this prospective study, 51 patients underwent [13N]-ammonia-PET MPI and CMR using a hybrid PET/MR device. Left ventricular end-systolic volumes (LVESV), end-diastolic volumes (LVEDV), stroke volumes (LVSV), ejection fractions (LVEF), and segmental wall motion were analyzed for both methods and were compared using correlational and Bland-Altman (BA) analysis; segmental wall motion was compared using ANOVA. The agreement between [13N]-ammonia-PET and CMR for LVEF was good, with minimal bias (- .6%) and narrow BA limits of agreement (- 7.9% to 6.8%), but [13N]-ammonia-PET systematically underestimated LV volumes, with high bias in LVESV (- 11.2 ml), LVEDV (- 28.9 ml), and LVSV (- 17.5 ml). Mean segmental wall motion in [13N]-ammonia-PET differed significantly among the corresponding normokinetic (6.6 ± 2 mm), hypokinetic (5.1 ± 2 mm), and akinetic (3.3 ± 2 mm) segments in CMR (P < .01). CONCLUSION: LVEF and LV wall motion can be accurately assessed using [13N]-ammonia-PET MPI, although LV volumes are significantly underestimated compared to CMR.

Sex hormones in SARS-CoV-2 susceptibility: key players or confounders?

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has a clear sex disparity in clinical outcomes. Hence, the interaction between sex hormones, virus entry receptors and immune responses has attracted major interest as a target for the prevention and treatment of SARS-CoV-2 infections. This Review summarizes the current understanding of the roles of androgens, oestrogens and progesterone in the regulation of virus entry receptors and disease progression of coronavirus disease 2019 (COVID-19) as well as their therapeutic value. Although many experimental and clinical studies have analysed potential mechanisms by which female sex hormones might provide protection against SARS-CoV-2 infectivity, there is currently no clear evidence for a sex-specific expression of virus entry receptors. In addition, reports describing an influence of oestrogen, progesterone and androgens on the course of COVID-19 vary widely. Current data also do not support the administration of oestradiol in COVID-19. The conflicting evidence and lack of consensus results from a paucity of mechanistic studies and clinical trials reporting sex-disaggregated data. Further, the influence of variables beyond biological factors (sex), such as sociocultural factors (gender), on COVID-19 manifestations has not been investigated. Future research will have to fill this knowledge gap as the influence of sex and gender on COVID-19 will be essential to understanding and managing the long-term consequences of this pandemic.