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.

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.

Imaging of heart disease in women: review and case presentation.

Cardiovascular diseases (CVD) remain the leading cause of mortality worldwide. Although major diagnostic and therapeutic advances have significantly improved the prognosis of patients with CVD in the past decades, these advances have less benefited women than age-matched men. Noninvasive cardiac imaging plays a key role in the diagnosis of CVD. Despite shared imaging features and strategies between both sexes, there are critical sex disparities that warrant careful consideration, related to the selection of the most suited imaging techniques, to technical limitations, and to specific diseases that are overrepresented in the female population. Taking these sex disparities into consideration holds promise to improve management and alleviate the burden of CVD in women. In this review, we summarize the specific features of cardiac imaging in four of the most common presentations of CVD in the female population including coronary artery disease, heart failure, pregnancy complications, and heart disease in oncology, thereby highlighting contemporary strengths and limitations. We further propose diagnostic algorithms tailored to women that might help in selecting the most appropriate imaging modality.

Cutting-Edge Imaging of Cardiac Metastases from Neuroendocrine Tumors: Lesson from a Case Series.

With the increasing availability of high-performance medical imaging for the management of patients with neuroendocrine tumors (NETs), a progressive growth of asymptomatic and incidentally detected cardiac metastases (CMs) has been observed in the recent years. In clinical practice, CMs of NENs are often incidentally detected by whole-body 68Ga-labeled somatostatin analogs or 18F-fluorodihydroxyphenylalanine positron emission tomography/computed tomography, and afterwards accurately characterized by cardiac magnetic resonance (CMR) and/or gated cardiac computed tomography when CMR is contraindicated or not available. The interpreting physician should familiarize with the main imaging features of CM, a finding that may be encountered in NETs patients more than previously thought. Herein, we present a case series of four patients with CMs from small-intestine NETs highlighting strengths and weaknesses of a multimodality imaging approach in clinical practice.

18F-DOPA PET/CT at the Forefront of Initial or Presurgical Evaluation of Small-Intestine Neuroendocrine Tumors.

Our objective was to compare the respective value of 68Ga-DOTATOC and 18F-DOPA PET/CT for initial staging or presurgical work-up of patients with small-intestine neuroendocrine tumors (SiNETs). Methods: This was a retrospective, multicenter, noninterventional investigation involving 53 non-surgically treated SiNET patients who underwent both 68Ga-DOTATOC and 18F-DOPA PET/CT within a 6-mo interval without surgical intervention or therapeutic change between the 2 PET/CT studies. Percentage detection rate was calculated according to per-region and per-lesion analyses. Sensitivity for primary tumor detection was assessed in 37 surgically treated patients, taking surgical results (76 SiNETs) as the diagnostic gold standard. Results: 68Ga-DOTATOC PET/CT and 18F-DOPA PET/CT individually identified at least 1 primary SiNET in 92% (34/37) of the patients. Intestinal tumor multifocality was confirmed by histology in 8 patients. 68Ga-DOTATOC and 18F-DOPA PET/CT were concordantly positive for tumor multifocality in 5 patients, discordantly positive in 2 patients, and concordantly negative in 1 patient. The detection rate for subdiaphragmatic nodal metastases on per-region-based analysis was 91% and 98% for 68Ga-DOTATOC and 18F-DOPA PET/CT, respectively (P = 0.18). 18F-DOPA PET/CT detected a higher number of abnormal subdiaphragmatic nodes (P = 0.009). Regarding mesenteric nodes only, 18F-DOPA PET/CT detected more positive regions (P = 0.005) and nodal lesions (P = 0.003) than 68Ga-DOTATOC PET/CT, including nodes at the origin of mesenteric vessels. For detection of distant metastases, 68Ga-DOTATOC and 18F-DOPA PET/CT performed equally well on a per-region-based analysis. As compared with 68Ga-DOTATOC, 18F-DOPA PET/CT detected more hepatic (P < 0.001), peritoneal (P < 0.001), and lung metastases (P < 0.001). Conclusion: 18F-DOPA PET/CT detected more lesions than 68Ga-DOTATOC PET/CT in the studied patients. The respective roles of the two should be discussed in terms of disease staging and treatment selection.

Diagnosis and staging of cardiac masses: additional value of CMR with 18F-FDG-PET compared to CMR with CECT.

PURPOSE: Characterization of malignant cardiac masses is usually performed with cardiac magnetic resonance (CMR) and staging with whole-body contrast-enhanced computed tomography (CECT). In this study, our objective was to evaluate the role of 18Fluor-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) with CMR for both characterization and staging of cardiac masses. METHODS: Patients with cardiac masses who underwent CMR, CECT, and 18F-FDG-PET were retrospectively identified. For the characterization of cardiac masses, we calculated the respective performances of CMR alone, 18F-FDG-PET alone, and the combination of 18F-FDG-PET and CMR. For staging, we compared head-to-head the respective performances of 18F-FDG-PET and CECT. Histology served as gold standard for malignancy, and response to anticoagulation for thrombus. RESULTS: In a total of 28 patients (median age 60.5 years, 60.7% women), CMR accurately distinguished malignant from benign masses with sensitivity (Se) of 86.7%, specificity (Sp) of 100%, positive predictive value (PPV) of 100%, negative predictive value (NPV) of 86.7%, and accuracy of 92.9%. 18F-FDG-PET demonstrated 93.3% Se, 84.6% Sp, 87.5% PPV, 91.7% NPV, and 89.3% accuracy. Combining CMR with 18F-FDG-PET allowed to benefit from the high sensitivity of 18F-FDG-PET (92.9%) and the excellent specificity of CMR (100%) for malignant diseases. For staging, 18F-FDG-PET outperformed CECT on per-patient (66.7% vs 55.6% correct diagnosis, respectively), per-organ (10 vs 7 organs, respectively), and per-lesion basis (> 29 vs > 25 lesions, respectively). CONCLUSION: Combining 18F-FDG-PET with CMR improved the characterization of cardiac masses compared to each modality alone. Additionally, the diagnostic performance of 18F-FDG-PET was better than CECT for staging. This study suggests that the combination of CMR and 18F-FDG-PET is the most effective for the characterization of cardiac masses and the staging of these lesions.

Heart-brain interactions in cardiac and brain diseases: why sex matters.

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.

Immunoreactivity of the SARS-CoV-2 entry proteins ACE-2 and TMPRSS-2 in murine models of hormonal manipulation, ageing, and cardiac injury.

Previous work indicates that SARS-CoV-2 virus entry proteins angiotensin-converting enzyme 2 (ACE-2) and the cell surface transmembrane protease serine 2 (TMPRSS-2) are regulated by sex hormones. However, clinical studies addressing this association have yielded conflicting results. We sought to analyze the impact of sex hormones, age, and cardiovascular disease on ACE-2 and TMPRSS-2 expression in different mouse models. ACE-2 and TMPRSS-2 expression was analyzed by immunostaining in a variety of tissues obtained from FVB/N mice undergoing either gonadectomy or sham-surgery and being subjected to ischemia-reperfusion injury or transverse aortic constriction surgery. In lung tissues sex did not have a significant impact on the expression of ACE-2 and TMPRSS-2. On the contrary, following myocardial injury, female sex was associated to a lower expression of ACE-2 at the level of the kidney tubules. In addition, after myocardial injury, a significant correlation between younger age and higher expression of both ACE-2 and TMPRSS-2 was observed for lung alveoli and bronchioli, kidney tubules, and liver sinusoids. Our experimental data indicate that gonadal hormones and biological sex do not alter ACE-2 and TMPRSS-2 expression in the respiratory tract in mice, independent of disease state. Thus, sex differences in ACE-2 and TMPRSS-2 protein expression observed in mice may not explain the higher disease burden of COVID-19 among men.

Mediastinal Masses: 18F-FDG-PET/CT Features Based on the International Thymic Malignancy Interest Group Classification.

Imaging plays a key role in the management of mediastinal masses. In an effort to standardize the analysis of the mediastinum, the International Thymic Malignancy Interest Group (ITMIG) has proposed a three compartments-based diagnostic classification, intended for clinicians and radiologists. Several articles have documented its usefulness to guide the diagnosis using cross-sectional imaging. Similarly, fluorine-18-radiolabeled fluorodeoxyglucose positron emission tomography combined to computed tomography (18F-FDG-PET/CT) can be useful in this setting, either as a first-line diagnostic technique, or in addition to cross-sectional imaging. In this article, which is thought as an aid for nuclear medicine physicians and radiologists, we aim to present, based on the ITMIG classification, the main mediastinal pathologies that can be observed with 18F-FDG-PET/CT, and the additional diagnostic value that can be expected from this technique. For this purpose, we segmented the mediastinum according to the ITMIG classification, and reviewed the available literature for each of the corresponding organs and/or disease. Given the importance of the clinical context for the interpretation of PET imaging, we presented each of the diseases according to: (1) their suggestive clinical context; (2) the suggestive features on nonenhanced CT (which is the standard in PET imaging); and (3) the typical 18F-FDG characteristics. The purpose of this article is to depict the main features of the most common mediastinal diseases that can be encountered with 18F-FDG-PET/CT, and to highlight its diagnostic value in this setting, alone or in combination with other imaging modalities.

Could FDG-PET imaging play a role in the detection of progressing atherosclerosis in HIV-infected patients?

Important progresses in the management of patients with human immunodeficiency virus, in particular the advent of new anti-retroviral therapies (ART), have turned this rapidly fatal condition into a controllable chronic disease with a life expectancy that approaches the one from the general population. Cardiovascular diseases have now become one of the leading causes of non-HIV-related mortality in this population. Several factors including the presence of HIV in the vascular wall and the development of dyslipidemia and alteration in body fat distribution under ART might play a role the progression of atherosclerosis in HIV-infected patients. The use of imaging biomarkers may help to identify the factors associated with an increased risk of cardiovascular events and select high-risk patients who will benefit the most from the early implementation of preventive treatments.

18F-FDG-PET/CT Imaging to Diagnose Septic Emboli and Mycotic Aneurysms in Patients with Endocarditis and Cardiac Device Infections.

PURPOSE OF REVIEW: This review analyzes recent studies evaluating the diagnostic value of 18F-FDG-PET/CT for the detection of peripheral emboli and secondary infectious foci in patients with infective endocarditis and cardiac device infections. RECENT FINDINGS: Detection of extracardiac septic localizations in patients with infective endocarditis and cardiac device infections is crucial, as it may impact the diagnosis, prognosis, and therapeutic management. Recent literature substantiated the clinical usefulness of 18F-FDG-PET/CT in this setting. 18F-FDG-PET/CT has proven its high diagnostic value for the detection of peripheral emboli in patients with infective endocarditis and cardiac device infections, substantially affecting patients' outcome and treatment. A multimodal approach, combining the high sensitivity of 18F-FDG-PET/CT with morphological imaging seems promising.

18F-FDG Uptake in Well-Differentiated Neuroendocrine Tumors Correlates with Both Ki-67 and VHL Pathway Inactivation.

BACKGROUND: 18F-FDG-PET scan positivity correlates with poor prognosis in neuroendocrine neoplasms (NEN). Glucose transporter 1 (GLUT1) and carbonic anhydrase 9 (CA9) are markers of aggressiveness in tumors. Together with von Hippel-Lindau protein (pVHL), they are involved in tumor cell metabolism via the hypoxia-inducible factor signaling pathway. The aim of this study was to compare, in a series of well-differentiated neuroendocrine tumors (NET), the 18F-FDG uptake and expression of the proliferation markers Ki-67, GLUT1, CA9, and pVHL. PATIENTS AND METHODS: This retrospective study included 27 patients with well-differentiated NET. 18F-FDG-PET images were evaluated by the maximum standardized uptake value (SUVmax). GLUT1, CA9, and pVHL were analyzed by immunohistochemistry. RESULTS: The NET were of pancreatic (n = 19), midgut (n = 4), duodenal (n = 1), esophageal (n = 1), rectal (n = 1), and pulmonary (n = 1) origin. Eight, 11, and 8 tumors were grade 1, 2, and 3, respectively. The mean/median Ki-67 index was 15/10% (1-60). The mean/median SUVmax was 6.2/5.2 (1.4-18.7). SUVmax correlated with greater tumor size (p = 0.03), higher expression of Ki-67 (p = 0.04), and lower expression of pVHL (p = 0.008). In the group of 16 NET with a low proliferative index (Ki-67 index <10%), 5/6 (83%) of the tumors with a high SUVmax had decreased pVHL expression (p = 0.0013). CONCLUSION: This study confirms that 18F-FDG-PET uptake correlates with both tumor size and proliferation in well-differentiated NET, and it highlights a subset of low-grade but 18F-FDG-PET-positive NET related to sporadic inactivation of the VHL pathway.

Characterization of 18F-Fluorodeoxyglucose Uptake Pattern in Noninfected Prosthetic Heart Valves.

BACKGROUND: 18F-Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) has been recently acknowledged as a diagnostic tool for prosthetic valve endocarditis, but its specificity is limited by uptake on noninfected valves. The objective of this study was to outline the main features of FDG uptake on PET/CT in patients with noninfected prosthetic heart valve (PHV). METHODS AND RESULTS: Our institution's PET/CT database was reviewed to identify patients with PHV, excluding those suspected of infection or who had received antibiotic treatment. PET indication, valve location, and type (biological/mechanical) and time from implantation were collected for each patient. Images with and without attenuation correction were considered for interpretation. The pattern of FDG uptake (absent, homogeneous, or heterogeneous) was recorded. Fifty-four PHVs (51 patients) were identified, including 32 biological valves. Indications for PET were oncology (n=26), suspicion of prosthetic valve endocarditis subsequently excluded (n=17), and history of vasculitis (n=11). A periprosthetic FDG uptake was present in 47 (87%) and 30 (56%) PHVs with and without attenuation correction, respectively, and the pattern was homogeneous in all but 4 (7%) and 3 (6%) PHVs, respectively. On quantitative analysis, maximum standardized uptake values was greater in mechanical than in biological valves (4.0 [2.4-8.0] versus 3.3 [2.1-6.1]; P=0.01) and in patients with vasculitis than in those referred for other indications. The uptake intensity did not differ before and 3 months after valve replacement. CONCLUSIONS: Noninfected PHVs frequently display homogeneous FDG uptake, which remains steady over time. Caution is, therefore, needed when interpreting FDG PET/CT in suspected prosthetic valve endocarditis, with specific attention to uptake pattern.

Differences in Alimentary Glucose Absorption and Intestinal Disposal of Blood Glucose After Roux-en-Y Gastric Bypass vs Sleeve Gastrectomy.

BACKGROUND & AIMS: Bariatric procedures, such as Roux-en-Y gastric bypass (RYGB) or vertical sleeve gastrectomy (VSG), are the most effective approaches to resolve type 2 diabetes in obese individuals. Alimentary glucose absorption and intestinal disposal of blood glucose have not been directly compared between individuals or animals that underwent RYGB vs VSG. We evaluated in rats and humans how the gut epithelium adapts after surgery and the consequences on alimentary glucose absorption and intestinal disposal of blood glucose. METHODS: Obese male rats underwent RYGB, VSG, or sham (control) operations. We collected intestine segments from all rats; we performed histologic analyses and measured levels of messenger RNAs encoding the sugar transporters SGLT1, GLUT1, GLUT2, GLUT3, GLUT4, and GLUT5. Glucose transport and consumption were assayed using ex vivo jejunal loops. Histologic analyses were also performed on Roux limb sections from patients who underwent RYGB 1-5 years after surgery. Roux limb glucose consumption was assayed after surgery by positron emission and computed tomography imaging. RESULTS: In rats and humans that underwent RYGB, the Roux limb became hyperplasic, with an increased number of incretin-producing cells compared with the corresponding jejunal segment of controls. Furthermore, expression of sugar transporters and hypoxia-related genes increased and the nonintestinal glucose transporter GLUT1 appeared at the basolateral membrane of enterocytes. Ingested and circulating glucose was trapped within the intestinal epithelial cells of rats and humans that underwent RYGB. By contrast, there was no hyperplasia of the intestine after VSG, but the intestinal absorption of alimentary glucose was reduced and density of endocrine cells secreting glucagon-like peptide-1 increased. CONCLUSIONS: The intestine adapts differently to RYGB vs VSG. RYGB increases intestinal glucose disposal and VSG delays glucose absorption; both contribute to observed improvements in glycemia.