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Objective To develop and validate the prognostic prediction model DU-VASC to assist the clinicians in decision-making regarding the use of platelet inhibitors (PIs) for the management of digital ulcers in patients with systemic sclerosis. Secondly, to assess the incremental value of PIs as predictor. Methods We analysed patient data from the European Scleroderma Trials and Research group registry (one time point assessed). Three sets of derivation/validation cohorts were obtained from the original cohort. Using logistic regression, we developed a model for prediction of digital ulcers (DUs). C-Statistics and calibration plots were calculated to evaluate the prediction performance. Variable importance plots and the decrease in C-statistics were used to address the importance of the predictors. Results Of 3710 patients in the original cohort, 487 had DUs and 90 were exposed to PIs. For the DU-VASC model, which includes 27 predictors, we observed good calibration and discrimination in all cohorts (C-statistic = 81.1% [95% CI: 78.9%, 83.4%] for the derivation and 82.3% [95% CI: 779.3%, 85.3%] for the independent temporal validation cohort). Exposure to PIs was associated with absence of DUs and was the most important therapeutic predictor. Further important factors associated with absence of DUs were lower modified Rodnan skin score, anti-Scl-70 negativity and normal CRP. Conversely, the exposure to phosphodiesterase-5 inhibitor, prostacyclin analogues or endothelin receptor antagonists seemed to be associated with the occurrence of DUs. Nonetheless, previous DUs remains the most impactful predictor of DUs. Conclusion The DU-VASC model, with good calibration and discrimination ability, revealed that PI treatment was the most important therapy-related predictor associated with reduced DU occurrence.

Background Deep learning image reconstructions (DLIR) have been recently introduced as an alternative to filtered back projection (FBP) and iterative reconstruction (IR) algorithms for computed tomography (CT) image reconstruction. The aim of this study was to evaluate the effect of DLIR on image quality and quantification of coronary artery calcium (CAC) in comparison to FBP. Methods One hundred patients were consecutively enrolled. Image quality–associated variables (noise, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR)) as well as CAC-derived parameters (Agatston score, mass, and volume) were calculated from images reconstructed by using FBP and three different strengths of DLIR (low (DLIR_L), medium (DLIR_M), and high (DLIR_H)). Patients were stratified into 4 risk categories according to the Coronary Artery Calcium - Data and Reporting System (CAC-DRS) classification: 0 Agatston score (very low risk), 1–99 Agatston score (mildly increased risk), Agatston 100–299 (moderately increased risk), and ≥ 300 Agatston score (moderately-to-severely increased risk). Results In comparison to standard FBP, increasing strength of DLIR was associated with a significant and progressive decrease of image noise (p < 0.001) alongside a significant and progressive increase of both SNR and CNR (p < 0.001). The use of incremental levels of DLIR was associated with a significant decrease of Agatston CAC score and CAC volume (p < 0.001), while mass score remained unchanged when compared to FBP (p = 0.232). The underestimation of Agatston CAC led to a CAC-DRS misclassification rate of 8%. Conclusion DLIR systematically underestimates Agatston CAC score. Therefore, DLIR should be used cautiously for cardiovascular risk assessment. Key Points • In coronary artery calcium imaging, the implementation of deep learning image reconstructions improves image quality, by decreasing the level of image noise. • Deep learning image reconstructions systematically underestimate Agatston coronary artery calcium score. • Deep learning image reconstructions should be used cautiously in clinical routine to measure Agatston coronary artery calcium score for cardiovascular risk assessment.

Background Myocardial perfusion imaging by positron emission tomography (PET-MPI) is the current gold standard for quantification of myocardial blood flow. F-18-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 F-18-flurpiridaz is feasible in mice. Methods Rest/stress PET-MPI was performed with F-18-flurpiridaz (0.6-3.0 MBq) in 27 mice aged 7-8 months. Regadenoson (0.1 mu g/g) was used for induction of vasodilator stress. Kinetic modeling was performed using a metabolite-corrected arterial input function. Image-derived myocardial F-18-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. K-1 ranged from 6.7 to 20.0 mL center dot cm(-3)center dot min(-1), while myocardial volumes of distribution (V-T) were between 34.6 and 83.6 mL center dot cm(-3). Of note, myocardial F-18-flurpiridaz uptake (%ID/g) was significantly correlated with K-1 at rest and following pharmacological vasodilation for all time intervals assessed. However, while Spearman's coefficients (r(s)) ranged between 0.478 and 0.681, R-2 values were generally low. In contrast, an excellent correlation of myocardial F-18-flurpiridaz uptake with V-T was obtained, particularly when employing the averaged myocardial uptake from 20 to 40 min post tracer injection (R-2 >= 0.98). Notably, K-1 and V-T were similarly sensitive to pharmacological vasodilation induction. Further, mean stress-to-rest ratios of K-1, V-T, and %ID/g F-18-flurpiridaz were virtually identical, suggesting that %ID/g F-18-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 F-18-flurpiridaz in mice, enabling high-throughput mechanistic CFR studies in rodents., Journal of Nuclear Cardiology, 30 (1), ISSN:1071-3581, ISSN:1532-6551

Cardiovascular disease and brain disorders, such as depression and cognitive dysfunction, are highly prevalent conditions and are among the leading causes limiting patient’s quality of life. A growing body of evidence has shown an intimate crosstalk between the heart and the brain, resulting from a complex network of several physiological and neurohumoral circuits. From a pathophysiological perspective, both organs share common risk factors, such as hypertension, diabetes, smoking or dyslipidaemia, and are similarly affected by systemic inflammation, atherosclerosis, and dysfunction of the neuroendocrine system. In addition, there is an increasing awareness that physiological interactions between the two organs play important roles in potentiating disease and that sex- and gender-related differences modify those interactions between the heart and the brain over the entire lifespan. The present review summarizes contemporary evidence of the effect of sex on heart–brain interactions and how these influence pathogenesis, clinical manifestation, and treatment responses of specific heart and brain diseases.

Despite a growing body of evidence, the distinct contributions of biological sex and the sociocultural dimension of gender to the manifestations and outcomes of ischaemic heart disease and heart failure remain unknown. The intertwining of sex-based differences in genetic and hormonal mechanisms with the complex dimension of gender and its different components and determinants that result in different disease phenotypes in women and men needs to be elucidated. The relative contribution of purely biological factors, such as genes and hormones, to cardiovascular phenotypes and outcomes is not yet fully understood. Increasing awareness of the effects of gender has led to efforts to measure gender in retrospective and prospective clinical studies and the development of gender scores. However, the synergistic or opposing effects of sex and gender on cardiovascular traits and on ischaemic heart disease and heart failure mechanisms have not yet been systematically described. Furthermore, specific considerations of sex-related and gender-related factors in gender dysphoria or in heart-brain interactions and their association with cardiovascular disease are still lacking. In this Review, we summarize contemporary evidence on the distinct effects of sex and gender as well as of their interactions on cardiovascular disease and how they favourably or unfavourably influence the pathogenesis, clinical manifestations and treatment responses in patients with ischaemic heart disease or heart failure.

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.

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.

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., 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.

Aims of the study: Virchow’s triad with stasis, activated coagulation, and endothelial damage is common in SARS-CoV2. Therefore, we sought to retrospectively assess whether the duration of prone position may serve as a risk factor for deep vein thrombosis in critically ill patients. Methods: In this single center retrospective study of a tertiary referral hospital, patients with acute respiratory distress syndrome (ARDS) due to COVID-19 pneumonia admitted to critical care underwent venous ultrasound screening for deep vein thrombosis (DVT). Data on DVT diagnosis, duration of prone positioning, demographic, respiratory, and laboratory parameters were retrospectively collected and compared between DVT and non-DVT patients. Results: 21 patients with ARDS from COVID-19 pneumonia were analyzed. DVT was detected in 11 (52%) patients (76.2% male, median age 64 (58; 68.5) years, median body mass index 31 (27; 33.8) kg/m2). In patients diagnosed with DVT, median prone ventilation had been maintained twice as long as compared to patients without DVT (57 (19; 72) versus 28 (0; 56.3) h, p = 0.227) on ICU day 5 with a trend towards longer prone position time (71 (19; 104) versus 28 (0; 73) h, p = 0.06) on ICU day 7. Conclusions: Prone ventilation and constitutional factors may constitute an additional risk factor for DVT in COVID-19 patients. Since recent studies have shown that therapeutic anticoagulation does not impact the occurrence of thromboembolic events, it may be worthwhile to consider mechanical factors potentially affecting blood flow stasis in this high-risk population. However, due to the limited number of patients, our observations should only be considered as hypothesis-generating. Future studies, sufficiently powered and preferably prospective, will be needed to confirm our hypothesis.

Context Menopause has been associated with adverse cardiovascular disease (CVD) risk profile, yet it is unclear whether the changes in CVD risk factors differ by reproductive stage independently of underlying ageing trajectories. Design The CoLaus study is a prospective population-based cohort study in Lausanne, Switzerland. Patients We used data from women at baseline and follow-up (mean: 5.6 ± 0.5 years) from 2003 to 2012 who did not use hormone therapy. We classified women into (i) premenopausal, (ii) menopausal transition, (iii) early (≤5 years) and (iv) late (>5 years) postmenopausal by comparing their menstruation status at baseline and follow-up. Measurements We measured fasting lipids, glucose and cardiovascular inflammatory markers. We used repeated measures (linear mixed models) for longitudinal analysis, using premenopausal women as a reference category. We adjusted analyses for age, medications and lifestyle factors. Results We used the data from 1710 women aged 35–75 years. Longitudinal analysis showed that the changes in CVD risk factors were not different in the other three menopausal categories compared to premenopausal women. When age was used as a predictor variable and adjusted for menopause status, most CVD risk factors increased, while interleukin-6 and interleukin-1β decreased with advancing age. Conclusion The current study suggests that women have a worsening cardiovascular risk profile as they age, and although menopausal women may have higher levels of cardiovascular risk factors compared to premenopausal women at any given time, the 5-year changes in cardiovascular risk factors may not depend on the reproductive stage., + ID der Publikation: unilu_64234 + Sprache: Englisch + Letzte Aktualisierung: 2023-07-07 09:54:37

Alterations in brain cholesterol homeostasis have been broadly implicated in neurological disorders. Notwithstanding the complexity by which cholesterol biology is governed in the mammalian brain, excess neuronal cholesterol is primarily eliminated by metabolic clearance via cytochrome P450 46A1 (CYP46A1). No methods are currently available for visualizing cholesterol metabolism in the living human brain; therefore, a noninvasive technology that quantitatively measures the extent of brain cholesterol metabolism via CYP46A1 could broadly affect disease diagnosis and treatment options using targeted therapies. Here, we describe the development and testing of a CYP46A1-targeted positron emission tomography (PET) tracer, 18 F-CHL-2205 ( 18 F-Cholestify). Our data show that PET imaging readouts correlate with CYP46A1 protein expression and with the extent to which cholesterol is metabolized in the brain, as assessed by cross-species postmortem analyses of specimens from rodents, nonhuman primates, and humans. Proof of concept of in vivo efficacy is provided in the well-established 3xTg-AD murine model of Alzheimer’s disease (AD), where we show that the probe is sensitive to differences in brain cholesterol metabolism between 3xTg-AD mice and control animals. Furthermore, our clinical observations point toward a considerably higher baseline brain cholesterol clearance via CYP46A1 in women, as compared to age-matched men. These findings illustrate the vast potential of assessing brain cholesterol metabolism using PET and establish PET as a sensitive tool for noninvasive assessment of brain cholesterol homeostasis in the clinic.

Effective risk factor modification is the prerequisite to prevent neurovascular disease such as stroke or vascular dementia. Non-traditional vascular risk factors (nt-vrfs) including stress significantly add to the risk of neurovascular disease arising from traditional vascular risk factors (t-vrfs). In order to discover sex-specific changes that may underlie previously reported inclines in the prevalence of neurovascular and cardiovascular disease in women, 10-year trends in the prevalence of vrfs in Switzerland were assessed.Anonymized data from 22,134 participants (51% women) of the governmental Swiss Health Survey, performed every 5 years (2007, 2012 and 2017), were obtained. Epidemiological parameters, t-vrfs and nt-vrfs were analyzed in a cross-sectional study design.Over the observation period, the number of women having full-time jobs increased considerably (2007 38%, 2012 39%, 2017 44%). This was accompanied by a substantial rise in the prevalence of nt-vrfs in women and men including stress at work (2007, not available; 2012 women/men 58%/60%; 2017 women/men 66%/65%), low locus of control (women/men: 2007 21%/19%, 2012 22%/19%, 2017 25%/22%) and sleep disorders (women/men: 2007 30%/22%, 2012 28%/20%, 2017 32%/26%). Amongst t-vrfs, only the prevalence of obesity and hypercholesterolemia increased over time in both sexes, whilst other t-vrfs remained stable (hypertension [27%], diabetes [5%]) or decreased (smoking [9.4 cigarettes/day]).A rise in women's economic participation alongside a higher affection with nt-vrfs in the female Swiss population emphasizes the need to improve vascular risk stratification and implement effective preventive measures for neurovascular and cardiovascular disease.

Objectives To assess the frequency, intensity, and clinical impact of [18F]FDG-avidity of axillary lymph nodes after vaccination with COVID-19 vaccines BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) in patients referred for oncological FDG PET/CT. Methods One hundred forty patients referred for FDG PET/CT during February and March 2021 after first or second vaccination with Pfizer-BioNTech or Moderna were retrospectively included. FDG-avidity of ipsilateral axillary lymph nodes was measured and compared. Assuming no knowledge of prior vaccination, metastatic risk was analyzed by two readers and the clinical impact was evaluated. Results FDG PET/CT showed FDG-avid lymph nodes ipsilateral to the vaccine injection in 75/140 (54%) patients with a mean SUVmax of 5.1 (range 2.0 – 17.3). FDG-avid lymph nodes were more frequent in patients vaccinated with Moderna than Pfizer-BioNTech (36/50 [72%] vs. 39/90 [43%] cases, p < 0.001). Metastatic risk of unilateral FDG-avid axillary lymph nodes was rated unlikely in 52/140 (37%), potential in 15/140 (11%), and likely in 8/140 (6%) cases. Clinical management was affected in 17/140 (12%) cases. Conclusions FDG-avid axillary lymph nodes are common after COVID-19 vaccination. The avidity of lymph nodes is more frequent in Moderna compared to that in Pfizer-BioNTech vaccines. To avoid relatively frequent clinical dilemmas, we recommend carefully taking the history for prior vaccination in patients undergoing FDG PET/CT and administering the vaccine contralateral to primary cancer. Key Points • PET/CT showed FDG-avid axillary lymph nodes ipsilateral to the vaccine injection site in 54% of 140 oncological patients after COVID-19 vaccination. • FDG-avid lymphadenopathy was observed significantly more frequently in Moderna compared to patients receiving Pfizer-BioNTech-vaccines. • Patients should be screened for prior COVID-19 vaccination before undergoing PET/CT to enable individually tailored recommendations for clinical management.

Purpose To assess the prognostic value of regional quantitative myocardial flow measures as assessed by 13N-ammonia positron emission tomography (PET) myocardial perfusion imaging (MPI) in patients with suspected coronary artery disease (CAD). Methods We retrospectively included 150 consecutive patients with suspected CAD who underwent clinically indicated 13 N-ammonia PET-MPI and who did not undergo revascularization within 90 days of PET-MPI. The presence or absence of a decreased global myocardial flow reserve (i.e., MFR Results Over a median follow-up of 50 months (IQR 38–103), 30 events occurred in 29 patients. Kaplan–Meier analysis showed significantly reduced event-free and overall survival in MFR groups 2 and 3 compared to MFR group 1 (log-rank: p = 0.015 and p = 0.013). In a multivariable Cox regression analysis, decreased regional MFR was an independent predictor for MACE (adjusted HR 3.44, 95% CI 1.17–10.11, p = 0.024) and all-cause death (adjusted HR 4.72, 95% CI 1.07–20.7, p = 0.04). Conclusions A decreased regional MFR as assessed by 13 N-ammonia PET-MPI confers prognostic value by identifying patients at increased risk for future adverse cardiac outcomes and all-cause death.

Background A growing body of evidence highlights sex differences in the diagnostic accuracy of cardiovascular imaging modalities. Nonetheless, the role of sex hormones in modulating myocardial perfusion and coronary flow reserve (CFR) is currently unclear. The aim of our study was to assess the impact of female and male sex hormones on myocardial perfusion and CFR. Methods Rest and stress myocardial perfusion imaging (MPI) was conducted by small animal positron emission tomography (PET) with [F-18]flurpiridaz in a total of 56 mice (7-8 months old) including gonadectomized (Gx) and sham-operated males and females, respectively. Myocardial [F-18]flurpiridaz uptake (% injected dose per mL, % ID/mL) was used as a surrogate for myocardial perfusion at rest and following intravenous regadenoson injection, as previously reported. Apparent coronary flow reserve (CFRApp) was calculated as the ratio of stress and rest myocardial perfusion. Left ventricular (LV) morphology and function were assessed by cardiac magnetic resonance (CMR) imaging. Results Orchiectomy resulted in a significant decrease of resting myocardial perfusion (Gx vs. sham, 19.4 +/- 1.0 vs. 22.2 +/- 0.7 % ID/mL, p = 0.034), while myocardial perfusion at stress remained unchanged (Gx vs. sham, 27.5 +/- 1.2 vs. 27.3 +/- 1.2 % ID/mL, p = 0.896). Accordingly, CFRApp was substantially higher in orchiectomized males (Gx vs. sham, 1.43 +/- 0.04 vs. 1.23 +/- 0.05, p = 0.004), and low serum testosterone levels were linked to a blunted resting myocardial perfusion (r = 0.438, p = 0.020) as well as an enhanced CFRApp (r = -0.500, p = 0.007). In contrast, oophorectomy did not affect myocardial perfusion in females. Of note, orchiectomized males showed a reduced LV mass, stroke volume, and left ventricular ejection fraction (LVEF) on CMR, while no such effects were observed in oophorectomized females. Conclusion Our experimental data in mice indicate that sex differences in myocardial perfusion are primarily driven by testosterone. Given the diagnostic importance of PET-MPI in clinical routine, further studies are warranted to determine whether testosterone levels affect the interpretation of myocardial perfusion findings in patients., European Journal of Nuclear Medicine and Molecular Imaging, 49, ISSN:1619-7070, ISSN:1619-7089

Background No methodology is available to distinguish truly reduced myocardial flow reserve (MFR) in positron emission tomography myocardial perfusion imaging (PET MPI) from seemingly impaired MFR due to inadequate adenosine response. The adenosine-induced splenic switch-off (SSO) sign has been proposed as a potential marker for adequate adenosine response in cardiac magnetic resonance (CMR). We assessed the feasibility of detecting SSO in nitrogen-13 ammonia PET MPI using SSO in CMR as the standard of reference. Methods and Results Fifty patients underwent simultaneous CMR and PET MPI on a hybrid PET/MR device with co-injection of a gadolinium-based contrast agent and nitrogen-13 ammonia during rest and adenosine-induced stress. In CMR, SSO was assessed visually (positive vs negative SSO) and quantitatively by calculating the ratio of the peak signal intensity of the spleen during stress over rest (SIR). In PET MPI, the splenic signal activity ratio (SAR) was calculated as the maximal standard uptake value of the spleen during stress over rest. The median SIR was significantly lower in patients with positive versus negative SSO in CMR (0.57 [IQR 0.49 to 0.62] vs 0.89 [IQR 0.76 to 0.98]; P P Conclusion Similarly to CMR, SSO can be detected in nitrogen-13 ammonia PET MPI. This might help distinguish adenosine non-responders from patients with truly impaired MFR due to microvascular dysfunction or multivessel coronary artery disease.

Objectives Coronary artery volume indexed to left myocardial mass (CAVi), derived from coronary computed tomography angiography (CCTA), has been proposed as an indicator of diffuse atherosclerosis. We investigated the association of CAVi with quantitative flow parameters and its ability to predict ischemia as derived from 13N-ammonia positron emission tomography myocardial perfusion imaging (PET-MPI). Methods Sixty patients who underwent hybrid CCTA/PET-MPI due to suspected CAD were retrospectively included. CAVi was defined as total coronary artery lumen volume over myocardial mass, both derived from CCTA. From PET-MPI, quantitative stress and rest myocardial blood flow (MBF) and myocardial flow reserve (MFR) were obtained and correlated with CAVi, and semi-quantitative perfusion images were analyzed for the presence of ischemia. Harrell’s c-statistic and net reclassification improvement (NRI) analysis were performed to evaluate the incremental value of CAVi over the CCTA model (i.e., stenosis > 50% and > 70%). Results CAVi correlated moderately with stress MBF and MFR (R = 0.50, p < 0.001, and R = 0.39, p = 0.002). Mean stress MBF and MFR were lower in patients with low (i.e., ≤ 20.2 mm3/g, n = 24) versus high (i.e., > 20.2 mm3/g, n = 36) CAVi (p < 0.001 for both comparisons). CAVi was independently associated with abnormal stress MBF (OR 0.90, 95% CI 0.82–0.998, p = 0.045). CAVi increased the predictive ability of the CCTA model for abnormal stress MBF and ischemia (c-statistic 0.763 versus 0.596, pdiff < 0.05 and 0.770 versus 0.645, pdiff < 0.05, NRI 0.84, p = 0.001 and 0.96, p < 0.001, respectively). Conclusions CAVi exhibits incremental value to predict both abnormal stress MBF and ischemia over CCTA alone. Key Points • Coronary artery volume indexed to left myocardial mass (CAVi), derived from coronary computed tomography angiography (CCTA), is correlated with myocardial blood flow indices derived from13N-ammonia positron emission tomography myocardial perfusion imaging. • CAVi is independently associated with abnormal stress myocardial blood flow. • CAVi provides incremental diagnostic value over CCTA for both abnormal stress MBF and ischemia.

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 18F-fluorodeoxyglucose (18F-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. 18F-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 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 Quantitative flow ratio (QFR) is a novel, adenosine-free method for functional lesion interrogation based on 3-dimensional quantitative coronary angiography and computational algorithms. We sought to investigate the diagnostic performance of QFR versus myocardial perfusion imaging positron emission tomography (MPI-PET), which yields the highest accuracy for detection of myocardial ischemia. Methods Diagnostic performance of QFR versus MPI-PET was assessed in consecutive patients undergoing both clinically indicated coronary angiography and 13N-ammonia MPI-PET within a six-month period. Results Out of 176 patients (439 coronary arteries), 19.3% were women. Percent area stenosis was 45 [32–58] %. Myocardial ischemia on 13N-ammonia MPI-PET was detected in 106 (24.1%) vessel territories and hemodynamic significance defined as contrast-flow vessel QFR ≤ 0.80 was observed in 83 (18.9%) vessels. Diagnostic accuracy, sensitivity, and specificity of contrast-flow vessel QFR for the prediction of myocardial ischemia on 13N-ammonia MPI-PET were 92.5 (95% CI 89.6–94.7) %, 73.6 (95% CI 64.1–81.7) %, and 98.5 (95% CI 96.5–99.5) %, respectively. The AUCs for contrast-flow vessel QFR, percent diameter stenosis, and percent area stenosis were 0.85 (95% CI 0.81–0.88, p Conclusions QFR, a novel diagnostic tool for functional coronary lesion assessment, provides good diagnostic agreement with MPI-PET and superior diagnostic accuracy for the detection of myocardial ischemia as compared to anatomic indices. Future studies will have to determine the non-inferiority of QFR to fractional flow reserve with respect to clinical outcomes.

[$^{18}$ F]Flurpiridaz is a recently developed positron emission tomography tracer that is currently being investigated in phase III clinical trials to measure myocardial blood flow. The relatively long physical half-life of fluorine-18 alongside the high spatial resolution and outstanding myocardium-to-background ratio fuels its potential to be the next gold standard for the early detection of coronary artery disease. Notwithstanding the expected widespread use of [$^{18}$ F]flurpiridaz, the reported multistep synthesis of its precursor for radiofluorination involves a hazardous alkylation step using carcinogenic ethylene oxide, and a low overall chemical yield of 7 %. In this work, we have improved the overall yield more than fivefold and concurrently replaced the hazardous step. Specificity of binding of [$^{18}$ F]flurpiridaz to mitochondrial complex 1 was demonstrated by in vitro autoradiography on mouse heart tissue sections. These results thus pave the way for assessing myocardial blood flow and coronary flow reserve in mouse models of cardiovascular disease.