ART-treated males with AIDS were divided into subgroups according to their CD4+ T-cell counts (<350 cells/μL and ≥350 cells/μL) and duration of disease . There was no significant decrease in left or right ventricular volume parameters or myocardial strain indices among the subgroups . In Pearson correlation analysis, CD4+ T-cell counts were not significantly correlated with biventricular volume parameters or left ventricular myocardial strain indices. In conclusion, ART-treated males with AIDS receiving ART therapy with a short disease duration (less than 3 years) might not develop obvious cardiac dysfunction as evaluated by routine CMR, so it is reasonable to appropriately extend the interval between cardiovascular follow-ups to more than 3 years.Cardiac complications are common in antiretroviral therapy-treated (ART-treated) acquired immune deficiency syndrome (AIDS) patients, and the incidence increases with age. Myocardial injury in ART-treated AIDS patients with a relatively longer disease duration has been evaluated. However, there is no relevant study on whether patients with a short AIDS duration have cardiac dysfunction. Thirty-seven ART-treated males with AIDS and eighteen healthy controls (HCs) were prospectively included for CMR scanning. Clinical data and laboratory examination results were collected. The ART-treated males with AIDS did not have significantly reduced biventricular ejection fraction, myocardial edema, or late gadolinium enhancement. Compared with the HCs, the biventricular volume parameters and left ventricle myocardial strain indices in ART-treated males with AIDS were not significantly reduced (all  Acquired immune deficiency syndrome (AIDS) is a serious global public health concern. In AIDS patients, mortality rates have decreased and survival duration has increased with increased use of antiretroviral treatment (ART). Therefore, the management of HIV/AIDS has become a long-term process. During this long process, multiple factors, including myocardial viral infections, immune activation, inflammation, metabolic abnormalities, nutritional deficiency, and so on, have been proposed to have negative impacts on the heart and to cause cardiac complications . Except Echocardiography is the main modality for evaluating cardiac complications in AIDS patients in long-term follow-up with a relatively lower cost. However, due to the intrinsic limitations of echocardiography, such as a lower accuracy of cardiac function evaluation, poor repeatability, and an inability to characterize the myocardium, cardiac magnetic resonance (CMR) is often recommended for the assessment of myocardial involvement and accurate function evaluation in AIDS patients, especially in those in whom cardiac complications are suspected and those having clinical symptoms. A CMR study indicated that HIV infection treated with ART is more likely to result in changes in myocardial structure and function and a higher prevalence of subclinical myocardial edema, myocardial fibrosis, and frequent pericardial effusions . Hollowa2); and (3) poor image quality impeding postprocessing. Finally, 2 patients who could not hold their breath, which resulted in poor image quality, were excluded, and 37 patients were included. Eighteen age-matched healthy males were enrolled as healthy controls (HCs). All participants signed informed consent forms. Basic information and laboratory data were collected.After approval by the Ethics Committee of Chengdu Public Health Clinical Medical Center, 39 male human immunodeficiency virus (HIV)-positive patients diagnosed with AIDS were prospectively enrolled and underwent enhanced CMR examination. Inclusion criteria were as follows: (1) 18 years < age < 70 years; (2) disease duration ≤ 36 months; (3) ART therapy initiation after diagnosis; (4) sinus heart rate and no cardiovascular history, including congenital heart disease, heart valve disease, cardiomyopathies, coronary heart disease, and so on; and (5) no malignant tumors or non-HIV-related respiratory diseases. Exclusion criteria were as follows: (1) CMR contraindications; (2) acute kidney injury or severe chronic kidney disease  , late gadolinium enhancement (LGE) images were obtained using the inversion recovery TrueFISP sequence (inversion time was based on TI scout) for the short-axis (slice thickness 8 mm) and 2-chamber and 4-chamber long-axis sections.All participants underwent a CMR scan using a 1.5-T whole-body scanner  in the supine position. Image acquisition was performed during the breath-holding period at the end of inspiration. A series of 8–12 continuous short-axis views of the left ventricle (LV) from the mitral valve to the level of the LV apex were obtained using steady-state free-precession sequences with the following parameters: repetition time, 4 ms; echo time, 2 ms; slice thickness, 6.0–8.0 mm; flip angle, 39°; field of view, 360 × 360 mmAll CMR data were analyzed using the commercially available software cvi42 . The series of short-axis cine images and 2-chamber and 4-chamber short-axis cine images were loaded into the short 3D module and issue feature tracking module. Epicardial and endocardial borders were traced manually to compute cardiac function parameters and myocardial deformation parameters. Biventricular function parameters included left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), left ventricular stroke volume (LVSV), left ventricular myocardial mass (LVM), right ventricular ejection fraction (RVEF), right ventricular end-diastolic volume (RVEDV), right ventricular end-systolic volume (RVESV), and right ventricular stroke volume (RVSV). LV remodeling was defined as the ratio of LVEDV to LV mass (LVRI). Myocardial strain indices included global radial strain (GRS), global circumferential strain (GCS), global longitudinal strain (GLS), global diastolic strain rate radial (GDSR), global diastolic strain rate circumferential (GDSC), and global diastolic strain rate longitudinal (GDSL). Segmental myocardial strain indices for the basal, middle, and apical parts of the LV were also acquired.t tests  or Kruskal–Wallis and Mann–Whitney U tests. Pearson’s test was performed to evaluate the relationship between CD4+ T-cell counts and parameters of cardiac function and myocardial strain. p-value < 0.05 was considered statistically significant.Statistical analyses were performed with SPSS . Continuous variables are expressed as the mean ± standard deviation or the median and interquartile range. Categorical variables are presented as frequencies (percentages) and were compared using the chi-square test. Normal distribution was tested with the Kolmogorov–Smirnov test. Continuous variables were compared using ANOVA and independent p > 0.05). The mean age of ART-treated males with AIDS was 37.62 ± 11.10 years old. All patients received ART therapy, and the duration was 20.58 ± 3.72 months. Blood CD4+ T-cell counts were 358.21 ± 57.41 cells/µL. Regarding HIV-related comorbidities, we found that syphilis was present in 5 (13.51%) patients, granulocytopenia was present in 3 (8.11%) patients, HIV-related pneumonia was present in 9 (24.32%) patients, metabolic syndrome was present in 10 (27.03%) patients, and oral fungal infection was present in 2 (5.41%) patients. No patients had cardiovascular symptoms, and electrocardiography and echocardiography findings were negative in all patients. Regarding myocardial injury biomarkers, no significant abnormality was found in the myocardial enzyme spectrum or high-sensitivity c-TnT in 37 patients.Thirty-seven ART-treated males with AIDS and eighteen HCs were included in this study. The baseline clinical characteristics are presented in p = 0.053), while LVMi  was similar between the groups after standardization by body surface area.No ART-treated males with AIDS had biventricular ejection fraction reduction, myocardial edema, or LGE. Biventricular function and LV deformation indices were compared between ART-treated males with AIDS and HCs (as shown in p = 0.307), RVEF , and LVRI  were not significantly decreased compared to those of HCs, nor were biventricular volume parameters significantly reduced . p > 0.05, see also In the group of ART-treated males with AIDS, LVEF . LVRI was not significantly different in the three groups . p > 0.05). A diastolic function comparison showed that GDSR , GDSC , and GDSL  were similar among the ART-treated AIDS male subgroups and HCs. Segmental analysis in basal, middle, and apical segments did not show significant decreases.According to the CD4+ T-cell counts, ART-treated males with AIDS were divided into two groups: those with CD4+ T-cell counts < 350 cells/μL (moderate or severe reduction of immune function) and those with CD4+ T-cell counts ≥ 350 cells/μL . The results of a comparison of cardiac function and myocardial strain are shown in p > 0.05). p > 0.05).According to disease duration, the ART-treated males with AIDS were divided into three subgroups: those with a disease duration of 1–12 months, 13–24 months, and 25–36 months. There was no significant difference in the remaining left and right ventricular function and structure in these three subgroups compared to the healthy control group (shown in p > 0.05).The results of the correlation analysis between CD4+ T-cell counts and CMR parameters are presented in This was the first CMR study that focused on the assessment of cardiac complications in ART-treated males with AIDS with a short disease duration (within 3 years), and no obvious cardiac dysfunction was found. ART is relatively safe for the heart over a short course of treatment. We recommend that the interval between cardiac follow-ups after the diagnosis of AIDS be appropriately extended for these patients.2 [49–77 g/m2] vs. 57 g/m2 [49–64 g/m2]), is closely related to cardiovascular adverse events, even though LVEF was still within the normal range. Nevertheless, neither LVRI nor biventricular functional parameters in ART-treated males with AIDS were different from those in HCs in this study. Subgroup analysis according to different disease severities based on CD4+ cell counts and disease duration did not show significant differences. Myocardial strain reflects the change in the length of myocardial fibers in the process of contraction and relaxation, and it is an early sensitive index to evaluate subclinical cardiac dysfunction [Previous studies that enrolled ART-treated AIDS patients with a mean disease duration of 90 months determined that AIDS patients can develop heart enlargement, ventricular septal thickening, and increased volume and myocardial mass, which further progress to diastolic and systolic dysfunction and even heart failure ,16,17. Tfunction ,20. Casefunction . Even infunction . The disfunction ,28,29,30p = 0.002) [In addition to cardiac function and myocardial strain, myocardial characterization in ART-treated males with AIDS was also performed. No evident myocardial edema or fibrosis was visually revealed by T2WI or LGE in our study. Acute HIV infection could cause myocarditis, revealed by obvious high intensity on T2WI and related symptoms, including chest pain, dyspnea, and palpitation . Negativ= 0.002) . The rel= 0.002) ,32. Howe= 0.002) ,32. A maDyslipidemia is extremely common in ART-treated AIDS patients. ART is also accompanied by lipodystrophy, redistribution, and insulin resistance. All these factors would increase cardiovascular risk in AIDS patients receiving ART ,34. AddiOne limitation of this study was that the sample size was too small. In the next study, we will expand the sample size and perform a follow-up CMR study. Furthermore, a mapping sequence was not applied in this study. We used only the sequences that are most commonly used in the clinic for evaluation. However, the technology we used in this study is mature in clinical applications and more accessible in medical institutions.ART-treated males with AIDS with a short disease duration may not develop obvious cardiac dysfunction as evaluated by routine CMR, so it is reasonable to appropriately extend the interval between cardiovascular follow-ups to more than 3 years.


Background: The role of rivaroxaban in patients with heart failure (HF) combined with left ventricular (LV) thrombus remains unknown in current guideline-directed anticoagulant therapy. The aim of this study was to investigate the impact on clinical outcomes of rivaroxaban compared to vitamin K antagonists (VKAs) in patients with HF combined with LV thrombus.Methods: We retrospectively extracted clinical, echocardiographic and follow-up data of HF patients  admitted at China-Japan Union Hospital of Jilin University from January 2017 to June 2021. A total of 198 patients with HF were identified with LV thrombus by echocardiography, 78 of them were managed with VKAs, 109 with rivaroxaban.Results: The median follow-up was 17.0 months (interquartile range: 6.0–24.0 months). High rates of major cardiovascular adverse events (MACEs) were observed in both the rivaroxaban and VKAs groups (49.5% vs. 57.7%). However, rivaroxaban versus VKAs observed a decrease in MACEs  and systemic embolism  but was not found to have a benefit with regard to LV thrombus resolution . Additionally, there was no significant between-group difference in the rate of International Society on Thrombosis and Hemostasis (ISTH) bleeding events.Conclusion: Our data found that in populations with HF combined with LV thrombus, the overall prognosis in both the rivaroxaban and VKAs groups was catastrophic. Although rivaroxaban improved the prognosis to some extent, a considerable need remains for new treatments to improve their clinical course. Despite the considerable progresses made during the last few years in heart failure (HF) management, there remain many aspects of HF therapy in clinical practice which lack strong trial evidence . AnticoaRivaroxaban, as a type of DOACs, has been observed with more positive results than VKAs in other clinical settings . Given tThis study is a retrospective observational study from a large tertiary referral center. We conducted a computerized search for all HF patients  admitted at China-Japan Union Hospital of Jilin University from January 2017 to June 2021. HF patients with LV thrombus on echocardiography, regardless of underlying disease causing the HF, were screened, and only patients with confirmed LV thrombus by two independent cardiologists and with documented routine follow-up were included in this study. In the event of disagreement between cardiologists reviewing the LV thrombus images, the images were submitted to another independent cardiologist for confirmation of the final review. We extracted information from the available medical record, and retrieved information regarding all-cause mortality, rehospitalization for cardiovascular events, systemic embolism, or bleeding events from routine clinical follow-up after LV thrombus diagnosis. Patients who had not yet documented a review event in the medical record were contacted individually by telephone to finalize the accuracy. Detailed definitions of HF and LV thrombus echocardiographic evaluation were presented in the According to current guidelines for the management of heart failure , anticoaAll clinical covariates including demographic data, past medical history, underlying disease, laboratory biochemical parameters, and echocardiographic data were collected through medical records or by interaction with patients or their family members. Those clinical covariates were associated with the prognosis of thrombosis and heart failure in previous studies . To addrIn this study, we mainly investigated the three endpoints: LV thrombus resolution, major adverse cardiovascular events (MACEs) and bleeding. LV thrombus status was defined based on the method of U test, as appropriate. Categorical variables were presented as number (%), and comparisons were performed using the χ2 or Fisher’s exact test as appropriate.Baseline characteristics were described as continuous or categorical variables. Continuous variables were represented as mean (SD) or median (IQR), and comparisons between groups were performed using Student’s t-test or Mann-Whitney p ≤ 0.05 in the univariate models were included in the multivariate Cox proportional hazards regression models to identify the independent effect of anticoagulant types on outcomes (The influence of anticoagulant types (Rivaroxaban vs. VKAs) on outcomes in patients with HF combined with LV thrombus was assessed by hazard ratios and their 95% confidence intervals (CIs) using Cox proportional hazard regression models. All clinical covariates were assessed by univariate Cox proportional hazards regression to determine whether they were significantly associated with outcomes. Then, covariates with outcomes . Meanwhioutcomes    , LV thrombus resolution that confirmed by echocardiography occurred in 46 of 78 (59.6%) patients in the VKAS group and 77 of 109 (70.6%) in the rivaroxaban group . Despite= 0.163) . Similar= 0.052) . In view= 0.052) .n = 45) in the VKAs group and 49.5% (n = 54) in the rivaroxaban group during the follow-up period (n = 10) in the VKAs group and 4.6% (n = 5) in the rivaroxaban group, respectively. Meanwhile, the incidence of rehospitalization for cardiovascular events was 26.9% (n = 21) in the VKAs group and 28.4% (n = 31) in the rivaroxaban group. After adjusting for potential confounders in the multivariate Cox proportional hazards regression model, in comparison with the VKAs group, HR for MACEs was lower in the rivaroxaban group . For systemic embolism, in the multivariate Cox regression model, relatively low HR was also observed in the rivaroxaban group , which was consistent with observation in the Fine-Gray model (Gray’s test p = 0.041)  . For all= 0.041) . Additio= 0.041) .p value for interaction = 0.05), but with a wide confidence interval in the non-ischemic heart disease population   .versus VKAs was not found to have a benefit with regard to LV thrombus resolution but observed a decrease in major adverse cardiovascular events and systemic embolism in the setting of the poor prognosis for both groups. Additionally, there was no significant between-group difference in the rate of bleeding events. These findings provide new insights into the anticoagulation management of LV thrombus in the HF setting.Advances in the understanding of the contribution of thrombin generation to thrombosis and the role of DOACs in thrombosis have prompted new anticoagulation paradigms. Since no clinical data on rivaroxaban in HF patients with LV thrombus have been reported, this retrospective study was performed. In this study, we investigated the impact on clinical outcomes of rivaroxaban compared to VKAs in HF patients with LV thrombus in terms of LV thrombus resolution, major adverse cardiovascular events, and bleeding events. In this population, rivaroxaban N = 79; odds ratio: 2.813; p = 0.03)  . These sversus VKAs was not found to have a benefit with regard to LV thrombus resolution; to test the stability of this finding, we used various statistical models, and the finding was generally consistent across statistical models, which was different from some previous LV thrombus-related studies in the non-HF setting , with no significant between-group difference in the rate of bleeding events . This rivaroxaban-related benefit was also reported in other large randomized clinical trials (RCTs)  . A post-s (RCTs) . In a pos (RCTs) . Furthers (RCTs) , which rFirst, the retrospective nature of this study predisposes it to selection bias; in particular, LV thrombus was only evaluated by echocardiography. Although we adopted an additional standardized procedure for the final confirmation of LV thrombus to reduce this bias , this may still contribute to an underestimation of the number of HF patients with LV thrombus. Second, event data was mostly obtained from medical records, which may produce omissions of clinical events. Although we conducted direct telephone follow-up to confirm clinical events, and data was obtained from a highly specialized large-scale heart failure center, which maintained a high level of data recruitment and follow-up, it may still have confounded the analysis of outcomes. Third, we were unable to evaluate the impact of antiplatelet therapy on LV thrombus in detail. Several studies have reported the beneficial effects of antiplatelet therapy on LV thrombus . MeanwhiOur data found that in populations with heart failure combined with LV thrombus, the overall prognosis in both the rivaroxaban and VKAs groups was catastrophic. Although rivaroxaban improved the prognosis compared with VKAs to some extent, a considerable need remains for new treatments to improve their clinical course. Further research is needed to provide more robust evidences.


The importance of cardiovascular biomarkers in clinical practice increased dramatically in the last years, and the interest extends from the diagnosis purpose to prognostic applications and response to specific treatment. Acute heart failure, ischemic heart failure, and COVID-19 infection represent different clinical settings that are challenging in terms of the proper prognostic establishment. The aim of the present review is to establish the useful role of sST2, the soluble form of the interleukin-1 receptor superfamily (ST2), physiologically involved in the signaling of interleukin-33 (IL-33)-ST2 axis, in the clinical setting of acute heart failure (HF), ischemic heart disease, and SARS-CoV-2 acute infection. Molecular mechanisms associated with the IL33/ST2 signaling pathways are discussed in view of the clinical usefulness of biomarkers to early diagnosis, evaluation therapy to response, and prediction of adverse outcomes in cardiovascular diseases. The search for useful biomarkers that can be adopted in clinical practice are of paramount importance, particularly in the acute phase of many diseases, in order to improve diagnostic precision as well as prognostic significance. Biomarkers increase their role in the management of many diseases; in the diagnostic procedure, the values of many biomarkers represent a crucial step in the diagnostic algorithm and in the decision tree. In the acute phase of the presentation of the pathology the adoption of specific and sensitive biomarkers can reduce time to act, optimize treatment, and improve knowledge of prognosis. In many cases biomarkers provide important contributions to the prognostic risk stratification and can be adopted to track the disease state in a follow-up analysis after discharge from the hospital.In the last 20 years, among the several biomarkers considered, attention on sST2 has significantly increased and it is now considered one of the most promising markers for the clinical management of many diseases.As a member of the interleukin-1 receptor superfamily, the protein ST2  presents with a transmembrane (ST2L) and soluble (sST2) isoforms. Since the discovery of interleukin-33 (IL-33) in 2005 .In this review, we focus on the possible role of the sST2 as a prognostic tool to stratify the outcome of patients admitted for acute heart failure alone or associated with COVID-19 infections.Localized on chromosome 2 (2q12), the ST2 gene encodes different isoforms through alternative promoter splicing. In particular, the transmembrane (ST2L) and the soluble (sST2) ones are particularly important in the inflammation and fibrosis processes .ST2L is expressed through several cells  and its role is tightly linked to the release of its natural ligand, the interleukin-33 (IL-33). Nowadays it is usual to consider the IL-33/ST2L axis to the full comprehension of the inflammatory cytokines/chemokines production and the successive regulation of innate and adaptive immune systems to promote inflammatory responses. Historically, the ST2  was described in advance of the detection of IL-33, with potential confusion in terminology. ST2 was originally cloned as an oncogene-induced gene from murine fibroblasts and later a second similar ST2 mRNA transcript was detected and predicted to code for a receptor, now identified as the transmembrane-bound ST2L receptor . The firIL-33, identified by Schmitz et al. in 2005 , belongsIn physiologic conditions, the intracellular localization of IL-33 is mainly in the nucleus, where it regulates gene expression in several ways; particularly as a direct action in suppressing the NF-kB-regulated genes that are necessary for pro-inflammatory signaling  but alsoIn pathological conditions such as in the necrosis processes, IL-33 reveals its “alarmin” nature and it is released by the cell in the extracellular space. By binding to the ST2L receptor, IL-33 exerts its cellular functions through several signal pathways. In particular, the molecular function is obtained by the action of the heterodimeric ST2L/IL-1RAcP complex on a variety of immune cells, where the IL-1R accessory protein (IL-1RAcP) plays an essential role by enhancing the affinity of IL-33 for ST2L.In more details, the binding of the IL-33 to ST2L allows the receptor to experience a conformational change, which enables the recruitment of IL-1RAcP . HeterodActivation of this pathway in Th2 cells leads to production of Th2 cytokines  .During wound healing, extracellular IL-33 interacts with the ST2L receptor and the complex of IL-33/ST2L activates myeloid differentiation primary response 88 (MyD88) intracellular cascades that drive production of type 2 cytokines (such as IL-13) from polarized Th2 cells. Most recently, tissue fibrosis, mucosal healing, and wound repairment were found to be additional possible actions of IL-33 during inflammation processes.The second variant of the ST2 gene expression is the circulating soluble ST2 (sST2), which is shorter than ST2L. It is identical in structure to the extracellular region of the long ST2L isoform except for nine additional amino acids at the C-terminus and it is obtained ,13 throuWhile pro-Brain Natriuretic Peptide (pro-BNP) is widely recognized as the gold standard marker for the diagnosis of acute heart failure (HF) in routine clinical practice, several studies have evaluated the use of different markers with potential prognostic value in HF patients; novel molecules such as sST2, emerge as potentially useful biomarkers, providing additional diagnostic and prognostic value with different and controversial findings in relation to the studied population and the end points evaluated. The American Heart Association/American College of Cardiology guidelines on the management of HF recommend the measurement of sST2, in addition to other fibrosis biomarkers, in patients with acute HF for a more appropriate stratification ; moreoveIn a prospective single-center study, pro-BNP and sST2 showed high diagnostic power for HF , but sST2 revealed stronger power to predict fatal events , as well as other markers of negative prognosis such as the use of inotropes or high lactate levels . The AmeIn a large Asian population, Yamamoto M et al. evaluated the additional clinical value of sST2, Pentraxin 3, Galectin-3, and high-sensitive cardiac troponin (hs-TnT) beyond BNP for risk stratification, showing that sST2 was associated with significant outcomes  in patients with acute decompensated HF solely in subjects with preserved ejection fraction . On the In the prospective cohort study, Wang Z. et al. evaluated 331 patients affected by acute HF according to sST2 levels, and followed progression for almost 2 years; patients with higher behaviors of sST2 had a higher left ventricular mass index, lower left ventricular ejection fraction, higher NYHA score and higher NT-proBNP levels; moreover this group showed the worst primary outcome  in all patients with acute AF .The Oulu Project Elucidating Risk of Atherosclerosis (OPERA) Survey collected data during a long-term follow-up (21 years), evaluating several data about morbidity and mortality. The main determinant of sST2 levels during the follow-up was smoking habit, and diabetes in the multivariate model male sex; levels of alanine aminotransferase (ALAT), high-density lipoprotein (HDL) cholesterol, and high-sensitive C-Reactive Protein (hsCRP) were associated with elevated sST2 levels. Moreover, sST2 levels were higher among subjects suffering from cardiovascular disease, cancer, mild cognitive decline, and diabetes. ST2 was found as an independent predictor of total mortality, evaluated with several covariates  .Conversely, in the Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA) cohort, sST2 was significantly associated with secondary endpoints  in older patients with chronic HF, whereas sST2 did not show prognostic significance regarding primary endpoint  pro-BNP, and C-reactive protein .Interestingly, a significant aspect resides in the variation in sST2 levels during the treatment of HF; in fact, more recent studies claim that continuous measurements greatly increase the amount of available prognostic information, and the use of sST2 as a monitoring tool .Beyond mortality and prognosis related to HF, Zhang Q et al. evaluated the usefulness and ability of sST2 to suggest the degree of coronary artery stenosis and to predict the development of adverse events 1 year after acute coronary syndrome (ACS). In this regard, the authors evaluated sST2 at discharge after hospitalization due to non-ST segment elevation acute coronary syndromes (NSTE-ACS) treated with percutaneous coronary intervention (PCI); the subgroup with higher levels of sST2 (>34.2 ng/mL) was associated with higher Gensini scores and multivessel disease, resulting as a marker predictive for the no-reflow phenomenon . Moreover, sST2 > 34.2 ng/mL had a significant role to predict 1-year prognosis, with a significantly higher rate of major cardiovascular and cerebrovascular events (MACCE) (HR 10.22) .An interesting registry-based study (registry SWEDEHEART) conducted on STEMI and NSTEMI patients followed for 6.6 years, showed that beyond other markers, sST2 was strongly useful to discriminate STEMI from NSTEMI patients, but lacking predictive ability to identify death or major adverse cardiovascular events; as a limit of this study, the lack of significance was probably due to the fact that a single dosage was taken at the time of admission, and not repeated during the long-term follow-up .Recently Park S. et al. evaluated the predictive ability of sST2 to detect left ventricular (LV) remodeling after ACS. Patients with reduced LV ejection fraction (EF < 50%), underwent PCI for ACS , evaluated echocardiographically at baseline and at a 3-month follow-up. During the follow-up, a significant correlation between sST2 and changes in LV end-diastolic/systolic volume index  was found but not in the changes in LVEF; moreover, the reduction in sST2 was more predominant in patients without adverse remodeling. Non-correlation was found in relation to ACS types. A multivariable analysis showed that sST2 variation was the most important determinant of LV remodeling following the revascularization of ACS .Recent studies showed that high levels of sST2 were detected during COVID-19 infection in patients without cardiovascular comorbidities positively correlated with CRP behaviors, suggesting an emerging role of sST2 as an inflammation marker during SARS-CoV-2 infection with stronger diagnostic value (ROC area 0.9896) , and assUnlike mild cases of COVID-19 infection characterized by an increased number of regulatory T (Treg) cells and a scavenger-like phenotype of alveolar macrophages  , in seveIn SARS-CoV2 patients, Luft T et al. found that in subgroup with severe disease  higher endothelial stress index (EASIX), useful predictor of endothelial activation, and life-threatening complications, was correlated to behaviors of several endothelial markers, as well as sST2, thrombomodulin, angiopoietin-2, CXCL8, CXCL9, and interleukin-18 .There are some promising preliminary results from trials using anti-ST2 antibodies such as Astegolimab , that caMoreover, a high prevalence of cardiovascular diseases among SARS-CoV-2-infected patients and vice versa has been reported, as well as significant risk of severe forms of COVID-19 among patients with preexisting HF ,34, alsoEvaluation of sST2 behaviors can be useful in order to detect those patients at high risk of developing myocardial injury due to ACE2-related cytotoxic effects, determining onset of HF, either de novo or an exacerbation of a chronic HF . LikewisMoreover, it is well-known that during SARS-CoV2 infection, acute respiratory distress syndrome (ARDS) is associated with right ventricle (RV) failure  and deveThe limit of the sST2 analysis in COVID-19 infection is provided by the few findings reported and most importantly, non-uniform studies in literature. The disease is still in a fast evolution phase, but future investigations must be designed to address the specific role for diagnostic and prognostic purposes, in particular with prospective follow-up studies.Although several molecules have been investigated in the last decades for diagnostic, therapeutic, and prognostic purposes, their use can have a diversified use in relation to clinical use and the different characteristics of the molecule. The IL-33/ST2 axis was initially evaluated in relation to the ability to influence neoplastic growth, and later in relation to cardiovascular diseases, inflammatory conditions, fibroproliferative diseases, autoimmune diseases, and systemic infections.Focusing attention on cardiovascular diseases, international guidelines and studies conducted on large populations suggest that, beyond its limited use on diagnosis of HF respect other biomarkers , the evaluation of sST2 is extremely useful in correlation to clinical data, in particular on the severity of the underlying cardiomyopathy, left ventricle hypertrophy, cardiac remodeling, ejection fraction, NYHA score, and finally to obtain prognostic information, especially regarding medium- to long-term mortality.Moreover, sST2 is correlated to the severity of ischemic heart disease; in fact, it strongly suggests poor prognosis with higher involvement of stenotic coronaries, high rate of coronary artery re-stenosis after percutaneous coronary intervention (PCI), worse myocardial remodeling post-PCI, and higher rate of major cardiovascular and cerebrovascular events during long-term follow-up.Finally, beyond bi-directional correlations between cardiovascular disease and SARS-CoV-2 infection, sST2 can be useful in evaluation and risk stratification in patients with SARS-CoV-2 infection; in fact, this biomarker is correlated with worse evolution of the infection, evaluated as ICU admission, mechanical ventilation needed, or in-hospital death.The role of the sST2 in COVID-19 is actually promising but still not completely clear. Further observational and prospective studies are needed to evaluate the diagnostic and the risk stratification function for the disease and its comorbidities. In particular, future analyses need to be designed to clarify some aspects, such as timing of sampling  or evaluation of its changes after specific treatment. The prognostic role, particularly promising, must be investigated through follow-up studies on medium- (months) and long-terms (years). In this case, serial samples together with clinical data and instrumental exams, can help to address the disease evolution and consequences.


In critically ill patients, standard transthoracic echocardiography (TTE) generally does not facilitate good image quality during mechanical ventilation. We propose a prone-TTE in prone positioned patients, which allows clinicians to obtain a complete apical four-chamber (A-4-C) view. A basic cardiac assessment can be performed in order to evaluate right ventricle function and left ventricle performance, even measuring objective parameters, i.e., tricuspid annular plane systolic excursion (TAPSE); pulmonary artery systolic pressure (PAP), from the tricuspid regurgitation peak Doppler velocity; RV end-diastolic diameter and its ratio to left ventricular end-diastolic diameter; the S’ wave peak velocity with tissue Doppler imaging; the ejection fraction (EF); the mitral annular plane systolic excursion (MAPSE); diastolic function evaluation by the mitral valve; and annular Doppler velocities. Furthermore, by tilting the probe, we can obtain the apical-five-chamber (A-5-C) view, which facilitates the analysis of blood flow at the level of the output tract of the left ventricle (LVOT) and then the estimation of stroke volume. Useful applications of this technique are hemodynamic assessment, titration of fluids, vasoactive drugs therapy, and evaluation of the impact of prone positioning on right ventricle performance and right pulmonary resistances. We believe that considerable information can be drawn from a single view and hope this may be helpful to emergency and critical care clinicians whenever invasive hemodynamic monitoring tools are not available or are simply inconvenient due to clinical reasons. During the COVID-19 pandemic, we observed many patients needing intensive care unit (ICU) admission and mechanical ventilation (MV) due to severe respiratory failure. In such conditions, subjects required sedation and myorelaxation to tolerate MV itself. Then, detailed cardiocirculatory evaluation and monitoring was necessary because of the effects of sedation and the high respiratory pressures. Indeed, patients under mechanical ventilation due to severe respiratory failure are often exposed to the risk of hemodynamic impairment because of continuous and even excessive intrathoracic positive pressure. Acute respiratory distress syndrome (ARDS) is one of the most frequent clinical conditions, during which the patient requires MV with a high pressure setting, aiming to re-open the collapsed and wet lung, and when it is not sufficient, the subject should be placed in prone position ,3,4. AllAdditionally, given the large number of patients requiring this type of care and the limited number of devices available, hemodynamic monitoring is often a logistic challenge. Consequently, cardiac ultrasound evaluation plays a crucial role in both diagnostics and monitoring, as it could be performed each time it is necessary as a noninvasive tool and then in a cost-effective way to achieve availability for all patients. Unfortunately, standard transthoracic echocardiography (TTE) generally does not allow for good image quality during mechanical ventilation. Thus, transesophageal echocardiography (TEE) has been reported to be the “gold standard” method to assess hemodynamic status .In critically ill patients, the prone position may be required due to acute respiratory disease syndrome or, as in recent times, to COVID-19 respiratory failure. In our opinion, one limitation to the use of TEE in prone patients may be the position of the neck and head, which may make introduction of the TEE probe difficult and sometimes unsafe.We recently described a new proposal for TTE in prone positioned patients . Our appWe performed the basic TTE assessment with the same probe orientation used in supine TTE: the probe marker pointing at the patient’s right shoulder, with the probe placed at the fourth or fifth intercostal space, achieving a A-4-C view which allows right ventricle (RV) function to be evaluated, in both an “eye-ball” and parametric way. Indeed, we were able to measure tricuspid annular plane systolic excursion (TAPSE); pulmonary artery systolic pressure (PAP), computed from the tricuspid regurgitation peak Doppler velocity and the right atrial pressure (RAP) estimated by either central venous pressure or inferior vena cava distensibility index; RV end-diastolic diameter and its ratio to left ventricular end-diastolic diameter; and the S’ wave peak velocity with tissue Doppler imaging, Moreover, left ventricle (LV) performance was explored ; the mitral annular plane systolic excursion (MAPSE); diastolic function evaluation by the mitral valve and annular Doppler velocities). Furthermore, by tilting the probe, we could obtain the apical-five-chamber (A-5-C) view, which allowed the analysis of the blood flow  at the level of the output tract of the left ventricle (LVOT) and then the theoretical estimation of the stroke volume (SV) by Doppler application . Indeed,Even from a single view, a plethora of information about cardiac performance can be obtained with this approach. MAPSE and TAPSE  provide information about the systolic function of the left ventricle and right ventricle, respectively, beyond the immediate “eye-ball” evaluation of their contractility and Ejection Fraction . More specifically, the measurement of the left ventricle output tract, even if not validated in the A-4-C view, and the application of the pulse-wave Doppler (PWD) on the aortic valve, measuring the Velocity Time Integral (VTI), allow stroke volume to be estimated and fluid responsiveness to be evaluated, with the abovementioned limitations. The PWD on the mitral valve produces the signal of the valve flaps’ velocity during the diastolic phase. The diastolic track consists of two waves (if sinus rhythm is present): the first wave (E) represents the rapid ventricle filling; a second wave (A) represents the atrial contraction that contributes to the late filling of the left ventricle. In case of atrial fibrillation, the A-wave is lacking. Their ratio (E/A) is an a-dimensional number normally higher than 1. Moreover, the deceleration time of the E-wave can rule out a severe diastolic dysfunction when it is >150 msec in case of pseudo-normality of the E/A ratio. Conversely, an E/A ratio < 1 indicates a mild diastolic dysfunction. Finally, if we apply Tissue Doppler Imaging (TDI) on the angle between the mitral valve plane and the lateral wall of the left ventricle, with the PWD, we can obtain and measure the velocity of this portion during the diastolic phase (the velocity of the E’ wave). The ratio E/E’ is a more precise evaluation of the diastolic function of the left ventricle.On the right heart side, if a tricuspid valve regurgitation is detected by color-mode application, continuous wave Doppler (CWD) on it allows measurement of the pressure gradient (in mmHg) between the right ventricle and the right atrium. This measurement summed to the central venous pressure gives an estimation of the systolic pulmonary artery pressure (PAPs). The central venous pressure is usually measured by a central venous catheter, which is routinely used in these patients. Alternatively, in this position, it could even be possible to obtain a transthoracic image of the IVC, placing the transducer horizontally in the right flank with the indicator pointing towards the patient’s head , and usiIn order to validate our approach, we performed a literature search of articles published from 1 January 2019 to February 2022, through the PubMed and Scopus platforms, using keywords such as “Trans-Thoracic Echocardiography AND Prone position”, “Cardiac Ultrasounds AND Prone Position”. For the purpose of this review, articles that studied the reliability of the TTE measurement obtained in prone position have been included.Despite the heterogeneity of the values measured by the various authors, each of them has been conducted with the purpose of demonstrating the feasibility of the TTE in prone position, both in healthy subjects and mechanically ventilated patients . This apConcerning the position used for the examination, Ugalde et al. previously described a case report about a patient receiving prone positioned TTE, but they partially modified the position of the patient using the “swimmer position” . The swiFocusing our analysis on the possible parameters to be recorded, Ugalde et al.  recentlyOther promising evaluations were performed by Gibson et al. , who demA novel approach was proposed by Marvaki et al.  and TahaNoteworthily, Santos et al.  focused Other interesting data were obtained by Roemer et al.  who studAll the information provided by prone position TTE, along with those from biomarker measurements and semi-invasive/invasive hemodynamic monitoring, may be crucial for a complete cardiocirculatory assessment in critically ill patients, especially if under respiratory support. Indeed, in patients under mechanical ventilation, several studies reported that diastolic dysfunction is associated with a failure of mechanical ventilation weaning, both when measured by E/A and E/E’ . Once agGenerally, the prone position could expose the patient to the risk of cardiocirculatory failure both in the ICU  and in the operating room, mainly for spine and brain surgery, due to abrupt blood redistribution and changes in vascular pressure and resistance. Turning a patient face down is contraindicated in case of increased intracranial pressure and hemodynamic instability . HemodynProne-TTE can be performed any time a hemodynamic assessment is needed and whenever there are not enough invasive hemodynamic monitoring tools available. We started to use TTE in prone position (TTEp) during the first wave of the COVID-19 outbreak in a patient requiring prone position mechanical ventilation and hemodynamic instability . He was TDI is an echocardiographic technique that uses Doppler principles to measure the velocity of myocardial motion that is related to diastolic function. TDI is less volume-load-dependent than the traditional Doppler technique and represents the best way to evaluate the diastolic performance of the heart. Reductions in TDI tricuspid annulus systolic velocity (<15 cm/s) have been described in many severe disease settings beyond chronic heart failure, such as myocardial infarction and pulmonary hypertension . As a suAlongside complete echocardiographic examination, focused echocardiography protocols are being proposed to quickly assess hemodynamics in a variety of acute clinical settings. In critical care, FICE, RUSH and FATE are quite well-known . Indeed,Noteworthily, some scientific societies released their recommendations on adoption of and training in focused ultrasound aimed at emergency and critical care physicians ,30. The Finally, beyond its diagnostic primary property, in skilled hands, TTEp may represent a valid alternative to traditional hemodynamic monitoring as it is safe, repeatable, and cost-saving, with the advantage of being available even during surges in demands of monitoring devices such as during pandemics or global health emergencies.Speaking of limitations of this approach, it is important to clarify that, while TAPSE and TDI are angle-independent measures, the same is not true for RV diameter and consequently right-to-left diameter ratio. As a matter of fact, RV diameter increases more and more as the probe approaches the parasternal line, resulting in an overestimation. Because of the crucial value of the RV diameter in the ventilated critically ill patients, this should be kept in mind when this measurement is obtained through TTEp.Another limitation has already been discussed and relates to the formula used to calculate the SV, which necessitates the radius of the LVOT. This problem is overcome using VTI as a surrogate value to evaluate the fluid responsiveness in this setting in a reliable way.In critically ill patients, standard transthoracic echocardiography generally does not facilitate good image quality during mechanical ventilation. We propose a prone-TTE in prone positioned patients, which allows clinicians to obtain a complete apical-four-chamber view; a basic evaluation can be performed in order to evaluate right ventricle function and left ventricle performance, even measuring objective parameters. Useful applications of this technique are hemodynamic assessment, titration of fluids and vasoactive drugs therapy, and evaluation of the impact of prone positioning on right ventricle performance and right pulmonary resistances. We believe that a wealth of information can be drawn from a single view and hope this may be helpful to emergency and critical care clinicians whenever invasive hemodynamic monitoring tools are not available or are simply inconvenient due to clinical reasons.


Current strategies for the evaluation of patients with chest pain have significantly changed thanks to the implemented potentiality of CT and MRI. The possible fatal consequences and high malpractice costs of missed acute coronary syndromes lead to unnecessary hospital admissions every year. CT provides consistent diagnostic support, mainly in suspected coronary disease in patients with a low or intermediate pre-test risk. Moreover, it can gain information in the case of cardiac involvement in pulmonary vascular obstructive disease. MRI, on the other hand, has a leading role in the condition of myocardial damage irrespective of the underlying inflammatory or stress related etiology. This article discusses how radiology techniques (CT and MRI) can impact the diagnostic workflow of the most common cardiac and vascular pathologies that are responsible for non-traumatic chest pain admissions to the Emergency Department. Most patients with cardiovascular emergencies present with chest pain and/or dyspnea. In this scenario, cardiac and non-cardiac etiologies must be taken into consideration . CardiacMyocarditis, a non-ischemic inflammatory disease of the myocardium is a cause of myocardial injury. It may be present in acute, fulminant, subacute and chronic forms . Injury CMR can identify three diagnostic features during an inflammatory myocardial process: edema, hyperemia, and necrosis or fibrosis .These three targets have been proposed for the diagnosis of acute myocarditis since the first consensus on Cardiovascular Magnetic Resonance (CMR) in Myocardial Inflammation in 2009—the “Lake Louise Criteria” (LLC)—and were subsequently revised and implemented in 2018 . TraditiHyperemia is the first stage of the inflammatory response, a process characterized by a change in blood flow in the damaged area. T1w images after the administration of a gadolinium-based contrast agent show an early and intense gadolinium enhancement compared with a noninflamed myocardium. Necrosis or fibrosis are both consequences of prolonged or severe tissue damage. This mechanism contributes to expanding the interstitium, increasing the volume of contrast media in the extracellular space. Necrosis and fibrosis might be evaluated using late gadolinium enhancement (LGE) imaging. Further, native T1 mapping is considered a useful tool for the evaluation of fibrosis. Furthermore, extracellular volume (ECV) is also considered an indicator of extracellular space expansion which typically occurs in fibrotic changes and can be assessed using T1 maps acquired pre- and post-administration of contrast media. It has a complementary role to LGE due to its ability to detect milder and diffuse fibrosis. The MyoRacer trial  found siDuring the SARS-CoV2 pandemic, several cases of myocarditis were observed. Similar to other viral pathogens, in this setting myocardial impairment was the result of direct viral cell damage and an autoimmune reaction. Consequently, CMR findings do not differ from what was already described in the Lake Louise criteria . As the pharmacokinetics of iodinated and gadolinium- based contrast agents are similar, the technique of late myocardial enhancement could also be applied on MDCT scans . DecreasPericardial inflammation may occur in quite a varied spectrum of conditions, including infections ; autoimmune diseases ; primary or secondary pericardial tumors; and chronic kidney disease. Furthermore, pericarditis may be triggered by direct pericardial injury  and cardiac damage . Up to 30% of cases have no defined cause and are consequently classified as idiopathic [CT and MRI can equally demonstrate pericardial effusion and pericardial thickening. A 4 mm thickness is conventionally indicated as the upper limit of normal, although it must be emphasized that pericarditis may be present even when the pericardium is within normal limits. Stranding of the pericardiac fat tissue can be an ancillary finding . MRI betIn some cases, acute inflammation causes permanent fibrotic changes and calcium deposition in the pericardium, resulting in constrictive pericarditis. In this condition, the stiffening of the pericardium affects ventricular filling. During inspiration RV filling prevails whereas during expiration LV filling is enhanced. The combination of morphologic changes in the pericardium, the remodeling (tubing) of ventricular cavities and biatrial enlargement are indirect signs of constrictive pericarditis. MRI, however, permits a direct demonstration of functional alterations: real-time cine sequences acquired during free-breathing show flattening of the interventricular septum at inspiration, followed by a return to normal convexity at the end of expiration . MINOCA occurs in 1–15% of acute MI cases in patients presenting with acute ST-segment elevation MI or non-ST segment elevation MI ,34. The CMR should be performed as soon as feasible after MINOCA is identified and it is therefore recommended within 7 days of presentation because delayed imaging can sometimes result in some features no longer being evident ,33. CMR CT coronary angiography (CCTA) is not indicated in these patients ,10 due tTakotsubo cardiomyopathy (TTC), also known as stress cardiomyopathy is an acute transient left ventricle dysfunction in which there is a sudden and reversible myocardial stunning in the absence of occlusive coronary artery disease . TTC is CMR is indicated in all patients presenting with suspected Takotsubo. CMR allows for the multiparametric quantification of myocardial tissue characteristics such as the absence of late gadolinium enhancement  and of late enhancement on delayed contrast sequences. These findings differentiate Takotsubo cardiomyopathy from anterior STEMI in which necrosis in the wall is present in most patients even when there is no-reflow or microvascular obstruction ,46. CMR Less frequent can be the reverse presentation (reverse Takotsubo syndrome) where the basal left myocardium can be affected .Acute coronary syndrome (ACS) refers to a group of diseases in which blood flow to the heart is decreased. It is a manifestation of CHD (coronary heart disease) which usually results in plaque disruption in the coronary arteries (atherosclerosis) and the formation of thrombus. In some cases, ACS may be due to vasospasm with or without underlying atherosclerosis, but in both cases it determines a reduction in blood flow to a part of the heart, resulting first in ischemia and then infarction.ACS includes several conditions: ST-segment elevation myocardial infarction (STEMI), non-ST-segment elevation myocardial infarction (NSTEMI), and unstable angina, and it is responsible for one third of total deaths in people older than 35 . In patients with suspected ACS, it will first be necessary to classify the patient in one of the two major sub-categories (STEMI and NSTEMI) and subsequently to distinguish the N-STEMI subtype (N-STEMI and unstable angina). STEMI is representative of an acute myocardial infarction with evidence of myocardial necrosis. Most of the patients presenting with ischemic symptoms and persistent ST-segment elevation on the electrocardiogram (ECG) > 20 min will show a typical rise in biomarkers of myocardial necrosis and progress to Q-wave myocardial infarction . Patientp < 0.001 and 49.6% vs. 22.7%, p < 0.001, respectively), reducing hospitalization times  and showing a better cost–benefit ratio than standard-of-care, thanks to the high negative predictive value of the CTA (excluding coronary stenosis > 50%) [In patients with a high risk of ACS, a prompt invasive coronary angiography and/or revascularization should be performed to salvage the viable myocardium. In such a scenario, radiology techniques (CT or MRI) should not be employed, they should only be used in the post-treatment phase for assessing the extent of myocardial damage. In contrast, in patients with a low to moderate risk of ACS alongside the non-invasive clinical instrumental standard evaluation, radiological techniques and in particular CT can play a key role in making a faster diagnosis, compared to standard of care ,52,53. Ss > 50%) ,55. The s > 50%) ,57,58. As > 50%) . A Type s > 50%) . Theorets > 50%)   studies using computational fluid dynamics gives the chance to enhance CT diagnostic accuracy. Moreover, in the emergency setting the use of FFR-CT allows a safer patient management thanks to the opportunity to detect, in the case of negative study, cardiac revascularization in chest pain patients. At the same time, it allows a significant reduction in medical cost .Alternatively, it is now possible to combine a coronary CT angiography with myocardial CT perfusion to define the hemodynamic significance of a coronary stenosis. Combined stress CT perfusion and CTA are strictly correlated to a shortened period of hospitalization and lower costs .Pulmonary Embolism (PE) is defined as the embolic occlusion of the pulmonary arterial system. In 95% of cases, it is caused by detached clots from deep vein thrombosis (DVT) of the lower extremities.The persistence or the recurrence of pulmonary embolic events is defined as Chronic Pulmonary Thromboembolism (CTEP) which can lead to delayed pulmonary hypertension (PH), a potentially fatal event ,65,66.The overall mortality of acute PE is 10–30%, making it the third most common cause of cardiovascular death and accounting for 300,000–370,000 deaths in Europe every year ,68.The wide spectrum of symptoms present in acute PE poses a diagnostic problem. It ranges from asymptomatic emboli with nonspecific clinical symptoms to massive life-threatening embolisms usually associated with right heart failure. The most common symptoms comprise chest pain, dyspnea, cough, hemoptysis and syncope but massive PTE can also lead to acute shock-inducing tachycardia, hypotension, tachy-/orthopnea, hypoxemia, hypocapnia, acute Right Ventricular Dysfunction (RVD) and even sudden death ,69. RVD indicates a potential emergency because it represents a rapidly progressive congestion syndrome resulting from impaired filling and/or reduced flow out of the right ventricle. It is triggered by acute pressure overload and is associated with a poor prognosis and a high risk of early mortality within 30 days .D-dimer is the most sensitive but non-specific diagnostic test for acute PE. Specificity improvements can be made using a cut-off value of 1000 ng/mL in patients with a low pre-test clinical probability score and of 500 ng/mL in patients with a moderate clinical probability score. Lower values safely exclude pulmonary embolism and unnecessary further diagnostic investigations . The rolTo assess the severity of PE, the commonly used CT Obstruction Index (CTOI) described by Qanadli et al.  calculatThe role of the Qanadli index in immediate risk stratification is validated but no correlation was observed between the obstruction index and prognosis ,84,85,86Rotzinger et al. recently reported that patients with acute PE, excluding those with comorbid cardiopulmonary or pulmonary neoplasms and with a CTOI greater than 40% had significantly higher mortality than those with a CTOI less than 20% .Complications of acute PTE include right ventricular dysfunction and pulmonary infarction. Signs of right heart strain on CTPA are an increased RV/LV diameter ratio > 1 measured on the short-axis or four chambers plane, an enlargement of the pulmonary trunk > 29 mm, flattening or inverse bowing of the interventricular septum and the reflux of contrast material into the inferior vena cava and hepatic veins ,77,78,87Ayöz et al.  describeRecently, further studies have focused attention on the additional parameters of RVD; Cozzi et al. showed that acute coronary sinus dilatation (>9 mm) increased the risk of all-cause death within 30 days . LangrouThe use of radiology techniques, CT, and MRI in the context of cardiac emergencies has enormously increased thanks to the massive use of cardio-synchronized CT in the last few years.CT in the emergency room allows for an expedited work-up of chest pain patients thanks to its very high (99%) negative predictive power for obstructive coronary artery disease. Appropriate CT utilization can lower healthcare costs and reduce radiation exposure. Nowadays, the gradual integration of FFR-CT or the use of pharmacological stress in the emergency settings may significantly improve the diagnostic performance in the near future.Modern scanners allow a real time evaluation, in addition to coronary circulation and assessment of the pulmonary and aortic vascular systems, translating the myth of the “one stop shop investigation” of the patient with chest pain into a clinical emergency routine.As it is intended for use within 3–5 days of symptom presentation and not in emergency conditions, MRI has recently become an irreplaceable tool in specific conditions once the presence of significant coronary obstructions has been excluded.Cardiac MRI has a wide range of applications which allows patient risk stratification if performed soon after the onset of chest pain. It can identify the myocardial area at risk, quantify eventual microvascular obstruction and identify intramyocardial hemorrhage.MRI can also give prognostic information thanks to the novel parametric mapping for tissue characterization. In some more complex emergency scenarios cardiac MRI helps to accurately classify those patients with atypical clinical features, such as MINOCA or Takotsubo cardiomyopathy cases. In doing so, different and adequate treatment can be determined.Regarding CT, recent technological advances have made it possible to significantly reduce the exposure dose problem and the speed of execution. A technological implementation is desirable regarding the MRI side, especially for the improvement of acquisition times which are decisive in the emergency settingRadiology has gained a central role in the diagnostic work-up of the patient with acute chest pain. Due to its potential, it has reached the chance to evaluate not only the vascular and coronary arteries but also to identify myocardial diseases associated with an emergency pain condition. It is therefore indispensable for the modern radiologist to acquire familiarity with diagnostic findings and the expression of acute cardiac damage, in order to potentially identify them in daily practice.


Here, we report an illustrative case from an ongoing study aimed to evaluate a novel, integrated approach for assessing postinfarct myocardial injury and inflammation using hybrid SST2 PET/MRI.Postinfarct inflammation and its resolution modulate ischemic injury after myocardial infarction (MI). While cardiac magnetic resonance imaging (MRI) is useful for assessing ventricular function, viability, and structural complications after MI, as well as detecting edema associated with acute inflammation, it lacks specificity for immune cell activity and may be less sensitive for identifying persistent, low-grade inflammation. Positron emission tomography (PET) imaging with A 36-year-old man with no prior medical history or cardiovascular risk factors presented with severe, sudden-onset chest pain. Cardiorespiratory examination was normal. The ECG showed sinus rhythm with evolving inferior ST-segment elevation without reciprocal changes. He underwent primary percutaneous coronary intervention to an occluded obtuse marginal branch of the left circumflex artery Figure A and 1B.9/L, with a neutrophilia. The C-reactive protein level was normal at <3 mg/L and the peak hsTnI (high-sensitivity Troponin I) concentration was >25 000 ng/L . Echocardiography demonstrated normal left ventricular function overall with a biplane ejection fraction of 58%, akinesis of the basal-to-mid inferolateral wall, and hypokinesis of the basal-to-mid anterolateral wall.Initial blood tests showed a total cholesterol level of 5.4 mmol/L, with triglycerides of 2.49 mmol/L, and an LDL of 3.39 mmol/L. The total white cell count was elevated at 18.4x 10https://www.clinicaltrials.gov; Unique identifier: NCT04073810), involving serial 68Ga-DOTATATE PET/MRI, cardiac MRI and CT coronary angiography with 2-year follow-up. Baseline PET/MRI was performed using a hybrid PET/MRI scanner  on day 11 post-MI. Fifty minutes after an injection of 238 MBq 68Ga-DOTATATE, PET images were acquired for 35-minutes in a cardiac bed position. Simultaneously acquired 3T MRI included 3-plane breath-held proton weighted, blood-suppressed single-shot fast-spin echo, 2D steady-state free precession cine imaging of the ventricles, T2-weighted edema imaging, T1 and T2 mapping, and late gadolinium enhancement. Static PET images were reconstructed from list mode data using iterative time-of-flight , and a free-breathing 2-point DIXON MR imaging sequence for attenuation correction.The patient was enrolled in a multi-modality cardiac imaging research study (REGISTRATION: URL: Video S1). There was increased signal on T2-weighted imaging in the basal anterolateral, mid inferolateral, and apical lateral walls signifying edema, with corresponding areas of near full-thickness and sub-endocardial late gadolinium enhancement  and Tissue-to-Background Ratios (TBRmax) normalized for blood-pool activity were 2.8 and 8.0, respectively, in the infarct versus 1.3 and 3.6 in the remote myocardium.Baseline MRI showed preserved left ventricular function, with persistent regional wall abnormalities ; and the British Heart Foundation .This work was additionally supported by the Cambridge BHF Centre of Research Excellence (18/1/34212); the NIHR Cambridge Biomedical Research Centre; the Cancer Research UK Cambridge Centre (A25177); and the Wolfson Brain Imaging positron emission tomography/magnetic resonance imaging team.None.Video S1


Cardiac structural and functional changes have been demonstrated in patients with non-alcoholic fatty liver disease (NAFLD). Because of the frequent association of NAFLD with hypertension, we aimed to examine the relationship of liver steatosis with left ventricular (LV) changes in patients with hypertension.In a cross-sectional study, we included 360 untreated, essential hypertensive patients who were free of major cardiovascular and renal complications. Liver steatosis was assessed by three different biochemical scores . Echocardiography was performed with standard B-mode and tissue-Doppler imaging.LV hypertrophy was present in 19.4% and LV diastolic dysfunction in 49.2% of patients who had significantly higher body mass index (BMI), blood pressure (BP), and homeostatic model assessment (HOMA) index and higher frequency of the metabolic syndrome and liver steatosis that was defined by presence of 2 or more positive scores. LV mass index increased progressively across patients who had none, 1, or 2 or more liver steatosis scores, with associated progressive worsening of LV diastolic function. LV mass index was significantly and positively correlated with age, BMI, BP, HOMA-index, LFS, and HSI. Logistic regression analysis showed that age, BP, and liver steatosis scores independently predicted LV hypertrophy and diastolic dysfunction. Liver steatosis independently predicted LV dysfunction but not LV hypertrophy even after inclusion in analysis of the HOMA-index.NAFLD is associated with LV hypertrophy and diastolic dysfunction in untreated patients with hypertension. In hypertension, NAFLD could contribute to LV diastolic dysfunction with mechanisms unrelated to insulin resistance. Non-alcoholic fatty liver disease (NAFLD) is the most frequent chronic hepatic disease embracing a continuum of conditions progressing from plain liver steatosis to non-alcoholic steatohepatitis, cirrhosis and, eventually, hepatocellular carcinoma . NAFLD iDiastolic heart failure is detected with growing frequency in patients with hypertension and LV hypertrophy  and is pAlthough NAFLD, hypertension, and LV hypertrophy could share a common denominator in decreased insulin sensitivity, no information is currently available on the possible relevance of fatty liver for cardiac abnormalities in hypertensive patients. We hypothesized that NAFLD could contribute to subclinical cardiac changes of hypertensive patients and that this contribution occurs independently of insulin resistance. Therefore, this study was conducted to investigate the relationships between biochemical scores of liver steatosis and cardiac structural and functional abnormalities in untreated hypertensive patients who were free of cardiac, vascular, and renal complications.2; alcohol consumption > 30 g/day in men, and > 20 g/day in women; secondary hypertension; glomerular filtration rate < 30 ml/min/1.73 m2; history of recent illness; any type of liver disease including hepatotropic viral infections; any type of coronary artery, cerebrovascular, and peripheral vascular disease. Smoking was categorized when subjects had smoked for more than 5°years and up to 1°year before enrolment. Definition of ethanol intake was obtained by use of the AUDIT questionnaire  and measurement of plasma glucose at 30, 60, 90, 120, and 180 min. According to current guidelines , patientBlood was collected by venipuncture into silicone-treated glass tubes after overnight fasting. After separation, plasma was stored at −80°C until assay. Measurements were done as previously reported . GlucoseLiver steatosis was assessed by three different biochemical scores: NAFLD Liver Fat Score (LFS), Fatty Liver Index (FLI), and Hepatic Steatosis Index (HSI) . These s2.7 for men and 47 g/m2.7 for women used to identify LV hypertrophy (e’) and late (a’) myocardial velocities of the septal and lateral walls were measured in the mitral valve annulus, with a Doppler beam positioned parallel to the LV wall. Average e’ and a’ values were obtained from measurements in three consecutive cardiac cycles and the e’/a’ and E/e’ ratios were calculated. LV diastolic dysfunction was considered according to guidelines  by the same researcher who was blind to the patients’ characteristics , 30. LV ertrophy . LV ejecertrophy . Early .The Kolmogorov-Smirnov test was used to assess normality of distribution of the study variables. Variables with skewed distribution were log transformed. Mean ± standard deviation is used to present normally distributed variables and median and [interquartile ranges] to present skewed variables. Categorical data are presented as absolute number and percentage. Frequency distributions were compared by the Pearson’ s chi-square test. Comparisons between 2 independent groups were done by the Student’s n = 70, 19.4%) or absence  of LV hypertrophy, and presence  or absence  of LV diastolic dysfunction. Patients with LV hypertrophy and diastolic dysfunction had significantly higher BMI, waist circumference, systolic and diastolic blood pressure, plasma insulin, and HOMA-index, whereas renal function, plasma lipid fractions, and liver enzymes were comparable with patients with normal LV mass and diastolic function. LV diastolic dysfunction was also associated with higher alcohol consumption. Higher frequency of concentric geometry and worse diastolic function were associated with LV hypertrophy, and greater LV mass was associated with LV diastolic dysfunction. LV systolic function was normal in all patients and this was irrespective of absence or presence of either LV hypertrophy or LV diastolic dysfunction.Three-hundred-sixty treatment-naïve, patients with essential hypertension  were included in this study. Clinical, biochemical, and cardiac ultrasound parameters are shown in P = 0.005), and in patients with LV diastolic dysfunction than in patients with normal diastolic function  (Liver steatosis was as defined by presence of at least 2 positive NAFLD scores and was found in 96 (26.7%) of the study patients. Among the remaining patients, 159 (44.2%) had no positive NAFLD score and 105 (29.2%) had only one. Prevalence of steatosis was significantly higher in patients with LV hypertrophy than in patients with normal LV mass  .e’ velocity, and e’/a’ ratio) progressively worsened. No differences were found in LV systolic function. Progressively higher frequency of LV hypertrophy and LV diastolic dysfunction , concentric remodeling , eccentric hypertrophy , and concentric hypertrophy . Distribution of patterns of LV geometry among patients with different liver steatosis grading showed progressive reduction in the frequency of the normal pattern with significant increase of concentric and eccentric hypertrophy  hypertrophy was included as the dependent variable in a multivariate logistic model, and age, sex, systolic blood pressure, obesity, creatinine clearance, and liver steatosis as independent variables . In thisA significant association of liver steatosis with LV abnormalities was reported in studies conducted in the general population and in subjects with NAFLD. Because LV changes have strong impact on the clinical outcome in hypertension, we examined the relationships of fatty liver with cardiac abnormalities in treatment-naïve, essential hypertensive patients who were free of major organ complications. Our results demonstrate that liver steatosis, as identified by use of biochemical scores, is significantly more frequent in hypertensive patients with LV hypertrophy and LV diastolic dysfunction than patients with normal hearts. LV mass index increases progressively and diastolic function worsens with increasing number of steatosis scores. Moreover, liver steatosis scores predict LV hypertrophy and diastolic dysfunction independently of blood pressure and obesity, although this association is independent of the HOMA-index only for LV diastolic dysfunction. This is the first demonstration that liver steatosis can contribute to LV changes in patients with essential hypertension. In these patients, mechanisms linking steatosis with LV diastolic dysfunction could be independent of insulin resistance.The association of NAFLD with heart abnormalities has recently ended up in the spotlight because of the strong relevance that this relationship holds for the risk of cardiac failure and cardiovascular death. Cross-sectional investigations conducted with use of either liver biopsy or elastography in patients with NAFLD reported increased frequency of LV hypertrophy, concentric remodeling, and diastolic dysfunction –14. SimiAlthough the epidemiologic link between hypertension and NAFLD has been clearly established , 18, infNonalcoholic fatty liver disease (NAFLD) has received broad recognition as the hepatic manifestation of the metabolic syndrome, since insulin resistance and oxidative stress are essential requirements for fat accumulation in hepatocytes , 37. InsLimitations of the study need to be underlined. The cross-sectional design limits the possibility to establish a direct functional link between fatty liver and LV changes, although independence of reported associations would suggest so. Also, definition of liver steatosis by use of biochemical scores has intrinsic limitations, although these scores were validated with liver biopsies and are commonly used in studies with large numbers of patients. To maximize their predictive power, three separate scores were combined to define different levels of probability of liver steatosis.Characterization of conditions that in addition to an increased hemodynamic load contribute to cardiac abnormalities in hypertension is critical for the development of effective strategies to prevent or treat these abnormalities. Subclinical hypertension-related cardiac changes increase the risk of major cardiovascular events and anticipate progression to heart failure with preserved ejection fraction. Because of the previous evidence of an association between NAFLD and LV changes, we investigated the relevance of fatty liver in an accurately selected group of untreated hypertensive subjects. This is the first study to demonstrate an independent association of liver steatosis with LV hypertrophy and diastolic dysfunction in hypertension. This association can have great relevance in this specific group of patients. In addition to insulin resistance, additional mechanisms might have a role in this association. These findings open a window on the possibility to develop new strategies to prevent and treat hypertensive heart disease. Future studies will test the possible benefits of nutritional and pharmacologic interventions on liver steatosis for cardiac protection in hypertension.The raw data supporting the conclusions of this article will be made available by the authors, upon reasonable request.The studies involving human participants were reviewed and approved by the Internal Review Board. The patients/participants provided their written informed consent to participate in this study.CC, GB, GS, and LS: conceptualization and design. CC, GB, and LS: writing the original draft. AD, DD, LB, AV, and GS: writing—review and editing. All authors acquisition of data, data analysis, and approved the final version of the manuscript, including the authorship list and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.


Adult GH deficiency (GHD) has been described as a heterogeneous condition characterized by many clinical modifications, such as metabolic alterations, impaired quality of life, and increased mortality. The clinical relevance of cardiac involvement remains, however, only partially elucidated.PubMed/Medline, EMBASE, Cochrane library, OVID and CINAHL databases were systematically searched until February 2022 for studies evaluating cardiac function and morphology by magnetic resonance imaging in adult patients with GHD. Effect sizes were pooled through a random-effect model.2, standardized mean difference (SMD) -0.60, 95%CI , p=0.03), lower end-diastolic-volume-index  and, after accounting for possible biases, lower mass-index . With respect to the right ventricle, a lower end-diastolic-volume-index  and a borderline-significant lower stroke-volume-index  could be observed. Data about the effect of GH replacement therapy highlighted a significant increase in left ventricular mass-index after treatment initiation .Four studies were considered in the meta-analysis. With respect to the left ventricle, GHD patients were characterized by a lower stroke-volume-index (-3.6 ml/mWith respect to the left ventricle, our results confirmed those retrieved by echocardiographic studies. In addition, significant alterations were demonstrated also for the right ventricle, for which echocardiographic data are nearly absent. This supports the thesis of a biventricular cardiac involvement in patients with GHD, with a similar pattern of morphological and functional alterations in both ventricles. Adult GH deficiency (GHD) is a heterogeneous disorder that may result from a variety of causes, including structural lesions, traumas, infiltrative diseases, surgery or irradiation to the pituitary gland and/or hypothalamus, or idiopathic dysfunction –5. Its dPhysiologically, the GH/IGF-I axis interacts with the cardiovascular system, both indirectly by acting on various metabolic cardiovascular risk factors, and directly by actively maintaining the structure and function of the normal adult heart, through the stimulation of cardiac growth and myocardial contractility –17. An iConcerning the cardiac effects of recombinant human GH (rhGH) replacement therapy in patients with adult GHD, a previous meta-analysis , based ode facto, unclear.As the authors themselves acknowledge, a limitation of this analysis, as well as of most studies evaluating cardiac structure and function in adult patients with GHD, is represented by the use of echocardiography, which suffers from a relatively low reproducibility with respect to other imaging techniques and, in particular, compared to magnetic resonance imaging (MRI). Moreover, the included studies were characterized by a significant heterogeneity in patient populations, with remarkable age-differences, and commonly with the enrollment of both childhood-onset and adult-onset GHD patients. These limitations may account at least in part for the sometimes-discrepant results obtained by different studies; moreover, they may have impaired the potential to correctly characterize subtler cardiac abnormalities in patients with GHD. This is particularly relevant when dealing with the structure and function of the right ventricle (RV) , 36, whoCompared to echocardiography, cardiac MRI represents a more reliable and reproducible technique for measuring cardiac volumes, mass, and function; its use in clinical research, given its enhanced precision and reproducibility, has been estimated to allow for a reduction in sample size of 80–95% to obtain equal statistical power compared to investigations based on conventional echocardiography . In factGiven these premises, cardiac MRI might provide finer information about cardiac alterations in patients with adult GHD, as well as their possible changes after the initiation of rhGH replacement therapy; in particular, it might answer to the question about if and how RV is involved. Some studies have been published in this regard –45, withThis study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines . The prost 2022: PubMed/Medline, EMBASE, Cochrane library, OVID, and CINAHL. The search strategy was performed using a combination of relevant database-specific search terms to identify pertinent studies about the evaluation of cardiac morphology and function by MRI in patients with adult GHD. The full search strategy is presented in Supplementary Material  unavailability of any of the outcomes of interest, as defined in the following subsection; (b) case reports or case series; (c) conference abstracts. In case of patient overlap between studies, the one with the largest sample size was considered.The following outcomes were assessed: (a) comparison of left and right ventricular morphology and function, as assessed by cardiac MRI, between patients with GHD and controls; (b) comparison of left and right ventricular morphology and function, as assessed by cardiac MRI, before and after treatment with rhGH in patients with GHD.More in detail, the MRI parameters that were evaluated were: (i) left ventricular ejection fraction (LVEF); (ii) left ventricular stroke volume index (LVSVi); (iii) left ventricular end-diastolic volume index (LVEDVi); (iv) left ventricular end-systolic volume index (LVESVi); (v) left ventricular mass index (LVMi); (vi) right ventricular ejection fraction (RVEF); (vii) right ventricular stroke volume index (RVSVi); (viii) right ventricular end-diastolic volume index (RVEDVi); (ix) right ventricular end-systolic volume index (RVESVi).Two authors  independently examined and extracted data from papers which met the inclusion criteria using pre-specified data extraction templates. For each eligible study, the following information were collected: (a) first author and publication year; (b) study design; (c) major selection criteria for each group; (d) matching criteria between GHD patients and controls; (e) number of subjects enrolled; (f) patients’ characteristics in terms of demographic data; (g) cardiac MRI data in GHD patients and controls, according to the parameters specified in the previous section; (h) cardiac MRI data in GHD patients before and after treatment with rhGH, according to the parameters specified in the previous section.The risk of bias was independently assessed for each included study by two authors . The twenty components of the AXIS tool   were use2 statistics and Cochran Q test were used to assess heterogeneity between studies. Statistical analysis was performed using STATA 17 .Continuous variables and categorical variables were reported as numbers and percentages, respectively. Comparisons between patients with GHD and controls were reported as mean difference and as standardized mean difference (SMD), expressed as Hedges’ g. Variations before and after rhGH treatment in patients with GHD were reported as mean paired differences. A random-effect restricted maximum likelihood model was adopted for statistical pooling of data. Higgins IA total of 165 records were identified in the initial literature search. Removal of duplicates led to an overall pool of 147 studies. An accurate title or abstract revision was sufficient to exclude 139 articles as not pertinent or not fulfilling our prespecified inclusion or exclusion criteria. The remaining 8 studies were assessed in full-text for eligibility , 49–52, Of note, in the study by Thomas et al. , all parData about LVEF –45 and L2, SMD -0.60, 95%CI , p=0.03) and LVEDVi  were significantly lower in GHD patients compared to controls. On the other hand, no significant differences between GHD patients and controls could be found in terms of LVEF  or LVESVi . When assessing LVMi, no overall differences could be found when pooling data from all studies ; this result, however, was remarkably influenced by the findings by Gonzalez et al.   was significantly lower in GHD patients compared to controls, and a borderline-significant trend towards a lower RVSVi  could also be observed. On the other hand, no significant differences between GHD patients and controls could be found in terms of RVEF  or RVESVi    in GHD patients compared to control. Overall, thus, the data about the EF demonstrate that, in each ventricle, the reduction in stroke volume and end-diastolic volume was roughly proportional, with an overall maintenance of the fraction of ventricular blood that is pumped into the pulmonary or systemic arterial system at each stroke.via the hypothalamic-pituitary-gonadal axis is also possible, given the known cross-talk between the two axes (With respect to cardiac mass, the available data were contrasting. Physiologically, the somatotroph axis is known to exert a direct anabolic function on the cardiac muscle, as widely demonstrated, for example, in experimental models –55 and itwo axes  and the two axes . Previoutwo axes –28. Moretwo axes . In the two axes , in whictwo axes –63. Whentwo axes , showingThe main strength of this meta-analysis is the selection of studies assessing cardiac morphology and function by MRI, which is currently considered the gold-standard imaging technique to this scope. In fact, with respect to echocardiography, it is endowed with a higher accuracy and reproducibility, reducing the risk of biases, and possibly improving the potential to correctly characterize subtler cardiac abnormalities in patients with GHD. This is of utmost relevance when examining RV parameters; in fact, the echocardiographic assessment of the RV suffers from significant challenges and limitations and, within the specific context of adult GHD, available echocardiographic studies provided almost no data about possible alterations in RV morphology and function.Our meta-analysis had also some limitations. First, the strength of the conclusions was limited by the small number of available studies; this limitation could reasonably be expected, in light of the low frequency of GHD together with the relatively limited availability of cardiac MRI; on the other hand, as already pointed out, cardiac MRI has the significant advantage of a better precision and reproducibility of estimates compared to echocardiography, and it has been estimated that a sample size reduced by 80–95% is still sufficient to obtain equal statistical power compared to echocardiographic studies . Second,In conclusion, the available evidence provided by cardiac MRI studies highlights significant left ventricular changes in patients with adult GHD, which are resumable as a reduction in end-diastolic volume, stroke volume, and ventricular mass; moreover, a significant increase in left ventricular mass can be seen after the initiation of rhGH replacement therapy. In addition, this is the first meta-analysis to provide a quantitative evaluation of the right ventricular involvement in GHD patients, for which echocardiographic data are nearly absent. Our results suggest a pattern of right ventricular alterations which is similar to left ventricular ones, with an almost significant reduction in end-diastolic volume and a statistical trend towards a lower stroke volume. This provides relevant information supporting a biventricular cardiac involvement in GHD, overall characterized by similar changes in left and right ventricular volumes and function.The original contributions presented in the study are included in the article/FB contributed to work conceptualization, data collection, data analysis and manuscript writing. NP, AB, CB, and MP-C contributed to data interpretation and manuscript writing. RF, SG, and EG supervised the manuscript drafting. VG contributed to work conceptualization, data collection, data analysis, manuscript writing and final draft supervision. All authors approved the manuscript in its final form.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.