Impact of reconstruction parameters on the accuracy of myocardial extracellular volume quantification on a first-generation, photon-counting detector CT.

BACKGROUND: The potential role of cardiac computed tomography (CT) has increasingly been demonstrated for the assessment of diffuse myocardial fibrosis through the quantification of extracellular volume (ECV). Photon-counting detector (PCD)-CT technology may deliver more accurate ECV quantification compared to energy-integrating detector CT. We evaluated the impact of reconstruction settings on the accuracy of ECV quantification using PCD-CT, with magnetic resonance imaging (MRI)-based ECV as reference. METHODS: In this post hoc analysis, 27 patients (aged 53.1 ± 17.2 years (mean ± standard deviation); 14 women) underwent same-day cardiac PCD-CT and MRI. Late iodine CT scans were reconstructed with different quantum iterative reconstruction levels (QIR 1-4), slice thicknesses (0.4-8 mm), and virtual monoenergetic imaging levels (VMI, 40-90 keV); ECV was quantified for each reconstruction setting. Repeated measures ANOVA and t-test for pairwise comparisons, Bland-Altman plots, and Lin's concordance correlation coefficient (CCC) were used. RESULTS: ECV values did not differ significantly among QIR levels (p = 1.000). A significant difference was observed throughout different slice thicknesses, with 0.4 mm yielding the highest agreement with MRI-based ECV (CCC = 0.944); 45-keV VMI reconstructions showed the lowest mean bias (0.6, 95% confidence interval 0.1-1.4) compared to MRI. Using the most optimal reconstruction settings (QIR4. slice thickness 0.4 mm, VMI 45 keV), a 63% reduction in mean bias and a 6% increase in concordance with MRI-based ECV were achieved compared to standard settings (QIR3, slice thickness 1.5 mm; VMI 65 keV). CONCLUSIONS: The selection of appropriate reconstruction parameters improved the agreement between PCD-CT and MRI-based ECV. RELEVANCE STATEMENT: Tailoring PCD-CT reconstruction parameters optimizes ECV quantification compared to MRI, potentially improving its clinical utility. KEY POINTS: • CT is increasingly promising for myocardial tissue characterization, assessing focal and diffuse fibrosis via late iodine enhancement and ECV quantification, respectively. • PCD-CT offers superior performance over conventional CT, potentially improving ECV quantification and its agreement with MRI-based ECV. • Tailoring PCD-CT reconstruction parameters optimizes ECV quantification compared to MRI, potentially improving its clinical utility.

Evaluation of a Tube Voltage-Based Contrast Media Adaptation in Coronary Computed Tomography Angiography Using Personalized Triphasic Injection Protocols: A Matched Case-Control Study.

RATIONALE AND OBJECTIVES: Coronary CT angiography (CCTA) has recently been established as a first-line test in patients with suspected coronary artery disease (CAD). Due to the increased use of CCTA, strategies to reduce radiation and contrast medium (CM) exposure are of high importance. The aim of this study was to evaluate the performance of automated tube voltage selection (ATVS)-adapted CM injection protocol for CCTA compared to a clinically established triphasic injection protocol in terms of image quality, radiation exposure, and CM administration MATERIAL AND METHODS: Patients undergoing clinically indicated CCTA were prospectively enrolled from July 2021 to July 2023. Patients underwent CCTA using a modified triphasic CM injection protocol tailored to the tube voltage by the ATVS algorithm, in a range of 70 to 130 kV with a 10 kV interval. The injection protocol consisted of two phases of mixed CM and saline boluses with different proportions to assure a voltage-specific iodine delivery rate, followed by a third phase of saline flush. This cohort was compared to a control group identified retrospectively and scanned on the same CT system but with a standard triphasic CM protocol. Radiation and contrast dose, subjective and objective image quality (contrast-to-noise-ratio [CNR] and signal-to-noise-ratio [SNR]) were compared between the two groups. RESULTS: The final population consisted of 120 prospective patients matched with 120 retrospective controls, with 20 patients in each kV group. The 120 kV group was excluded from the statistical analysis due to insufficient sample size. A significant CM reduction was achieved in the prospective group overall (46.0 [IQR 37.0-52.0] vs. 51.3 [IQR 40.1-73.0] mL, p < 0.001) and at all kV levels too (all pairwise p < 0.001). There were no significant differences in radiation dose (6.13 ± 4.88 vs. 5.97 ± 5.51 mSv, p = 0.81), subjective image quality (median score of 4 [3-5] vs. 4 [3-5], p = 0.40), CNR, and SNR in the aorta and the left anterior descending coronary artery (all p > 0.05). CONCLUSION: ATVS-adapted CM injection protocol allows for diagnostic quality CCTA with reduced CM volume while maintaining similar radiation exposure, subjective and objective image quality.

Intra-individual comparison of coronary CT angiography-based FFR between energy-integrating and photon-counting detector CT systems.

BACKGROUND: Coronary computed tomography angiography (CCTA)-based fractional flow reserve (CT-FFR) allows for noninvasive determination of the functional severity of anatomic lesions in patients with coronary artery disease. The aim of this study was to intra-individually compare CT-FFR between photon-counting detector (PCD) and conventional energy-integrating detector (EID) CT systems. METHODS: In this single-center prospective study, subjects who underwent clinically indicated CCTA on an EID-CT system were recruited for a research CCTA on PCD-CT within 30 days. Image reconstruction settings were matched as closely as possible between EID-CT (Bv36 kernel, iterative reconstruction strength level 3, slice thickness 0.5 mm) and PCD-CT (Bv36 kernel, quantum iterative reconstruction level 3, virtual monoenergetic level 55 keV, slice thickness 0.6 mm). CT-FFR was measured semi-automatically using a prototype on-site machine learning algorithm by two readers. CT-FFR analysis was performed per-patient and per-vessel, and a CT-FFR ≤ 0.75 was considered hemodynamically significant. RESULTS: A total of 22 patients (63.3 ± 9.2 years; 7 women) were included. Median time between EID-CT and PCD-CT was 5.5 days. Comparison of CT-FFR values showed no significant difference and strong agreement between EID-CT and PCD-CT in the per-vessel analysis (0.88 [0.74-0.94] vs. 0.87 [0.76-0.93], P = 0.096, mean bias 0.02, limits of agreement [LoA] -0.14/0.19, r = 0.83, ICC = 0.92), and in the per-patient analysis (0.81 [0.60-0.86] vs. 0.76 [0.64-0.86], P = 0.768, mean bias 0.02, LoA -0.15/0.19, r = 0.90, ICC = 0.93). All included patients were classified into the same category (CT-FFR > 0.75 vs ≤0.75) with both CT systems. CONCLUSIONS: CT-FFR evaluation is feasible with PCD-CT and it shows a strong agreement with EID-CT-based evaluation when images are similarly reconstructed.

Chest CT opportunistic biomarkers for phenotyping high-risk COVID-19 patients: a retrospective multicentre study.

OBJECTIVE: To assess the value of opportunistic biomarkers derived from chest CT performed at hospital admission of COVID-19 patients for the phenotypization of high-risk patients. METHODS: In this multicentre retrospective study, 1845 consecutive COVID-19 patients with chest CT performed within 72 h from hospital admission were analysed. Clinical and outcome data were collected by each center 30 and 80 days after hospital admission. Patients with unknown outcomes were excluded. Chest CT was analysed in a single core lab and behind pneumonia CT scores were extracted opportunistic data about atherosclerotic profile (calcium score according to Agatston method), liver steatosis (≤ 40 HU), myosteatosis (paraspinal muscle F < 31.3 HU, M < 37.5 HU), and osteoporosis (D12 bone attenuation < 134 HU). Differences according to treatment and outcome were assessed with ANOVA. Prediction models were obtained using multivariate binary logistic regression and their AUCs were compared with the DeLong test. RESULTS: The final cohort included 1669 patients (age 67.5 [58.5-77.4] yo) mainly men 1105/1669, 66.2%) and with reduced oxygen saturation (92% [88-95%]). Pneumonia severity, high Agatston score, myosteatosis, liver steatosis, and osteoporosis derived from CT were more prevalent in patients with more aggressive treatment, access to ICU, and in-hospital death (always p < 0.05). A multivariable model including clinical and CT variables improved the capability to predict non-critical pneumonia compared to a model including only clinical variables (AUC 0.801 vs 0.789; p = 0.0198) to predict patient death (AUC 0.815 vs 0.800; p = 0.001). CONCLUSION: Opportunistic biomarkers derived from chest CT can improve the characterization of COVID-19 high-risk patients. CLINICAL RELEVANCE STATEMENT: In COVID-19 patients, opportunistic biomarkers of cardiometabolic risk extracted from chest CT improve patient risk stratification. KEY POINTS: • In COVID-19 patients, several information about patient comorbidities can be quantitatively extracted from chest CT, resulting associated with the severity of oxygen treatment, access to ICU, and death. • A prediction model based on multiparametric opportunistic biomarkers derived from chest CT resulted superior to a model including only clinical variables in a large cohort of 1669 patients suffering from SARS- CoV2 infection. • Opportunistic biomarkers of cardiometabolic comorbidities derived from chest CT may improve COVID-19 patients' risk stratification also in absence of detailed clinical data and laboratory tests identifying subclinical and previously unknown conditions.

Extracellular volume fraction (ECV) derived from pre-operative computed tomography predicts prognosis in patients undergoing transcatheter aortic valve implantation (TAVI).

AIMS: Transcatheter aortic valve implantation (TAVI) is the treatment of choice for high-risk patients with severe aortic stenosis (AS). A portion of TAVI recipients has no long-term clinical benefit, and myocardial fibrosis may contribute to unfavourable outcomes. We aimed to assess the prognostic value of an interstitial fibrosis marker, extracellular volume fraction (ECV), measured at planning computed tomography (CT) before TAVI. METHODS AND RESULTS: From October 2020 to July 2021, 159 consecutive patients undergoing TAVI planning CT were prospectively enroled. ECV was calculated as the ratio of myocardium and blood pool differential attenuations before and 5 min after contrast administration, pondered for haematocrit. A composite endpoint including heart failure hospitalization (HFH) and death was collected by telehealth or in-person follow-up visits in the 113 patients constituting the final study population. Cox proportional hazards model was used to assess association between ECV and the composite endpoint.Median follow-up was 13 (11-15) months. The composite endpoint occurred in 23/113 (20%) patients. These patients had lower aortic valve mean pressure gradient [39 (29-48) vs. 46 (40-54) mmHg, P = 0.002] and left ventricular and right ventricular ejection fraction [51 (37-69) vs. 66 (54-74)%, P = 0.014; 45 (31-53) vs. 49 (44-55)%, P = 0.010] and higher ECV [31.5 (26.9-34.3) vs. 27.8 (25.3-30.2)%, P = 0.006]. At multivariable Cox analysis, ECV higher than 31.3% was associated to increased risk of death or HFH at follow-up (hazard ratio = 5.92, 95% confidence interval 2.37-14.75, P < 0.001). CONCLUSION: In this prospective observational cohort study, ECV measured at TAVI planning CT predicts the composite endpoint (HFH or death) in high-risk severe AS patients.

Continuous sensing of IFNα by hepatic endothelial cells shapes a vascular antimetastatic barrier.

Hepatic metastases are a poor prognostic factor of colorectal carcinoma (CRC) and new strategies to reduce the risk of liver CRC colonization are highly needed. Herein, we used mouse models of hepatic metastatization to demonstrate that the continuous infusion of therapeutic doses of interferon-alpha (IFNα) controls CRC invasion by acting on hepatic endothelial cells (HECs). Mechanistically, IFNα promoted the development of a vascular antimetastatic niche characterized by liver sinusoidal endothelial cells (LSECs) defenestration extracellular matrix and glycocalyx deposition, thus strengthening the liver vascular barrier impairing CRC trans-sinusoidal migration, without requiring a direct action on tumor cells, hepatic stellate cells, hepatocytes, or liver dendritic cells (DCs), Kupffer cells (KCs) and liver capsular macrophages (LCMs). Moreover, IFNα endowed LSECs with efficient cross-priming potential that, along with the early intravascular tumor burden reduction, supported the generation of antitumor CD8+ T cells and ultimately led to the establishment of a protective long-term memory T cell response. These findings provide a rationale for the use of continuous IFNα therapy in perioperative settings to reduce CRC metastatic spreading to the liver.

Colorectal cancer remains one of the most widespread and deadly cancers worldwide. Poor health outcomes are usually linked to diseased cells spreading from the intestine to create new tumors in the liver or other parts of the body. Treatment involves surgically removing the initial tumors in the bowel, but patient survival could be improved if, in parallel, their immune system was 'boosted' to destroy cancer cells before they can form other tumors. Interferon alpha is a small protein which helps to coordinate how the immune system recognizes and deactivates foreign agents and cancerous cells. It has recently been trialed as a colorectal cancer treatment to prevent tumors from spreading to the liver, but only with limited success. This partly because interferon-alpha is usually administered in high and pulsed doses, which cause severe side effects through the body. Instead, Tran, Ferreira, Alvarez-Moya et al. aimed to investigate whether continuously delivering lower amounts of the drug could be a better approach. This strategy was tested on mice in which colorectal cancer cells had been implanted into the wall of the large intestine. Continuous administration minimized the risk of the implanted cancer cells spreading to the liver while also creating fewer side effects. The team was able to identify an optimum delivery strategy by varying how much interferon-alpha the animals received and when. Further experiments also revealed a new mechanism by which interferon-alpha prevented the spread of colorectal cancer. Upon receiving continuous doses of the drug, a group of liver cells started to generate a physical barrier which stopped cancer cells from being able to invade the organ. The treatment also promoted long-term immune responses that targeted diseased cells while being safe for healthy tissues. If confirmed in clinical trials, these results suggest that colorectal patients undergoing tumor removal surgery may benefit from also receiving interferon-alpha through continuous delivery.

AI-SCoRE (artificial intelligence-SARS CoV2 risk evaluation): a fast, objective and fully automated platform to predict the outcome in COVID-19 patients.

PURPOSE: To develop and validate an effective and user-friendly AI platform based on a few unbiased clinical variables integrated with advanced CT automatic analysis for COVID-19 patients' risk stratification. MATERIAL AND METHODS: In total, 1575 consecutive COVID-19 adults admitted to 16 hospitals during wave 1 (February 16-April 29, 2020), submitted to chest CT within 72 h from admission, were retrospectively enrolled. In total, 107 variables were initially collected; 64 extracted from CT. The outcome was survival. A rigorous AI model selection framework was adopted for models selection and automatic CT data extraction. Model performances were compared in terms of AUC. A web-mobile interface was developed using Microsoft PowerApps environment. The platform was externally validated on 213 COVID-19 adults prospectively enrolled during wave 2 (October 14-December 31, 2020). RESULTS: The final cohort included 1125 patients (292 non-survivors, 26%) and 24 variables. Logistic showed the best performance on the complete set of variables (AUC = 0.839 ± 0.009) as in models including a limited set of 13 and 5 variables (AUC = 0.840 ± 0.0093 and AUC = 0.834 ± 0.007). For non-inferior performance, the 5 variables model (age, sex, saturation, well-aerated lung parenchyma and cardiothoracic vascular calcium) was selected as the final model and the extraction of CT-derived parameters was fully automatized. The fully automatic model showed AUC = 0.842 (95% CI: 0.816-0.867) on wave 1 and was used to build a 0-100 scale risk score (AI-SCoRE). The predictive performance was confirmed on wave 2 (AUC 0.808; 95% CI: 0.7402-0.8766). CONCLUSIONS: AI-SCoRE is an effective and reliable platform for automatic risk stratification of COVID-19 patients based on a few unbiased clinical data and CT automatic analysis.

Myosteatosis Significantly Predicts Persistent Dyspnea and Mobility Problems in COVID-19 Survivors.

Background: Persistent symptoms including dyspnea and functional impairment are common in COVID-19 survivors. Poor muscle quality (myosteatosis) associates with poor short-term outcomes in COVID-19 patients. The aim of this observational study was to assess the relationship between myosteatosis diagnosed during acute COVID-19 and patient-reported outcomes at 6 months after discharge. Methods: Myosteatosis was diagnosed based on CT-derived skeletal muscle radiation attenuation (SM-RA) measured during hospitalization in 97 COVID-19 survivors who had available anthropometric and clinical data upon admission and at the 6-month follow-up after discharge. Dyspnea in daily activities was assessed using the modified Medical Research Council (mMRC) scale for dyspnea. Health-related quality of life was measured using the European quality of life questionnaire three-level version (EQ-5D-3L). Results: Characteristics of patients with (lowest sex- and age-specific tertile of SM-RA) or without myosteatosis during acute COVID-19 were similar. At 6 months, patients with myosteatosis had greater rates of obesity (48.4 vs. 27.7%, p = 0.046), abdominal obesity (80.0 vs. 47.6%, p = 0.003), dyspnea (32.3 vs. 12.5%, p = 0.021) and mobility problems (32.3 vs. 12.5%, p = 0.004). Myosteatosis diagnosed during acute COVID-19 was the only significant predictor of persistent dyspnea (OR 3.19 [95% C.I. 1.04; 9.87], p = 0.043) and mobility problems (OR 3.70 [95% C.I. 1.25; 10.95], p = 0.018) at 6 months at logistic regression adjusted for sex, age, and BMI. Conclusion: Myosteatosis diagnosed during acute COVID-19 significantly predicts persistent dyspnea and mobility problems at 6 months after hospital discharge independent of age, sex, and body mass. Clinical Trial Registration: [www.ClinicalTrials.gov], identifier [NCT04318366].

Hybrid PET/MRI in Staging Endometrial Cancer: Diagnostic and Predictive Value in a Prospective Cohort.

AIM: The assessment of deep myometrial invasion (MI) and lymph node involvement is of utmost importance in the preoperative staging of endometrial cancer (EC). Imaging parameters derived respectively from MRI and PET have shown good predictive value. The main aim of the present study is to assess the diagnostic performance of hybrid 18F-FDG PET/MRI in EC staging, with particular focus on MI and lymphnodal involvement detection. PATIENTS AND METHODS: Prospective monocentric study including 35 patients with biopsy-proven EC undergoing preoperative 18F-FDG PET/MRI (December 2018-March 2021) for staging purpose. Histological examination was the reference standard. PET (SUVmax, SUVmean with a threshold of 40% of SUVmax-SUVmean40, metabolic tumor volume, total lesion glycolysis) and MRI (volume index [VI], total tumor volume, tumor volume ratio [TVR], mean apparent diffusion coefficient, minimum apparent diffusion coefficient) parameters were calculated on the primary tumor, and their role in predicting EC risk group, the presence of lymphovascular space invasion (LVSI), and MI was assessed. Receiver operating characteristics analysis was used to assess the predictive value of PET and MRI parameters on EC characteristics. RESULTS: Patients' median age was 66.57 years (SD, 10.21 years). 18F-FDG PET/MRI identified the primary tumor in all patients. Twenty-two of 35 patients had high-risk EC and 13/35 low-risk disease; 13/35 presented LVSI, 22/35 had deep MI at histological examination, and 13/35 had p53 hyperexpression.PET/MRI was able to detect lymphnodal involvement with high accuracy and high specificity (sensitivity of 0.8571, specificity of 0.9286, accuracy of 0.9143), also showing a high negative predictive value (NPV) for lymphnodal involvement (NPV of 0.9630, positive predictive value [PPV] of 0.7500).The assessment of deep MI using PET/MRI correctly staged 27 patients (77.1%; sensitivity of 0.7273, specificity of 0.8462, accuracy of 0.7714), with also a good PPV (PPV of 0.8889, NPV of 0.647).MRI-derived total tumor volume, VI, and TVR were significant in predicting EC groups (high-risk vs low-risk patients) (P = 0.0059, 0.0235, 0.0181, respectively). MRI-derived volume, VI, TVR, and PET-derived metabolic tumor volume and total lesion glycolysis were able to predict LVSI (P = 0.0023, 0.0068, 0.0068, 0.0027, 0.01394, respectively). Imaging was not able to predict grading, presence of deep MI, nor hyperexpression of p53. CONCLUSIONS: 18F-FDG PET/MRI has good accuracy in preoperative staging of EC; PET and MRI parameters have synergic role in preoperatively predicting LVSI, with MRI parameters being also predictive for EC risk group.

The hidden interplay between sex and COVID-19 mortality: the role of cardiovascular calcification.

Recent clinical and demographical studies on COVID-19 patients have demonstrated that men experience worse outcomes than women. However, in most cases, the data were not stratified according to gender, limiting the understanding of the real impact of gender on outcomes. This study aimed to evaluate the disaggregated in-hospital outcomes and explore the possible interactions between gender and cardiovascular calcifications. Data was derived from the sCORE-COVID-19 registry, an Italian multicentre registry that enrolled COVID-19 patients who had undergone a chest computer tomography scan on admission. A total of 1683 hospitalized patients (mean age 67±14 years) were included. Men had a higher prevalence of cardiovascular comorbidities, a higher pneumonia extension, more coronary calcifications (63% vs.50.9%, p<0.001), and a higher coronary calcium score (391±847 vs. 171±479 mm3, p<0.001). Men experienced a significantly higher mortality rate (24.4% vs. 17%, p=0.001), but the death event tended to occur earlier in women (15±7 vs. 8±7 days, p= 0.07). Non-survivors had a higher coronary, thoracic aorta, and aortic valve calcium score. Female sex, a known independent predictor of a favorable outcome in SARS-CoV2 infection, was not protective in women with a coronary calcification volume greater than 100 mm3. There were significant differences in cardiovascular comorbidities and vascular calcifications between men and women with SARS-CoV2 pneumonia. The differences in outcomes can be at least partially explained by the different cardiovascular profiles. However, women with poor outcomes had the same coronary calcific burden as men. The presumed favorable female sex bias in COVID-19 must therefore be reviewed in the context of comorbidities, especially cardiovascular ones.

Impact of clinical and subclinical coronary artery disease as assessed by coronary artery calcium in COVID-19.

BACKGROUND AND AIMS: The potential impact of coronary atherosclerosis, as detected by coronary artery calcium, on clinical outcomes in COVID-19 patients remains unsettled. We aimed to evaluate the prognostic impact of clinical and subclinical coronary artery disease (CAD), as assessed by coronary artery calcium score (CAC), in a large, unselected population of hospitalized COVID-19 patients undergoing non-gated chest computed tomography (CT) for clinical practice. METHODS: SARS-CoV 2 positive patients from the multicenter (16 Italian hospitals), retrospective observational SCORE COVID-19 (calcium score for COVID-19 Risk Evaluation) registry were stratified in three groups: (a) "clinical CAD" (prior revascularization history), (b) "subclinical CAD" (CAC >0), (c) "No CAD" (CAC = 0). Primary endpoint was in-hospital mortality and the secondary endpoint was a composite of myocardial infarction and cerebrovascular accident (MI/CVA). RESULTS: Amongst 1625 patients (male 67.2%, median age 69 [interquartile range 58-77] years), 31%, 57.8% and 11.1% had no, subclinical and clinical CAD, respectively. Increasing rates of in-hospital mortality (11.3% vs. 27.3% vs. 39.8%, p < 0.001) and MI/CVA events (2.3% vs. 3.8% vs. 11.9%, p < 0.001) were observed for patients with no CAD vs. subclinical CAD vs clinical CAD, respectively. The association with in-hospital mortality was independent of in-study outcome predictors (age, peripheral artery disease, active cancer, hemoglobin, C-reactive protein, LDH, aerated lung volume): subclinical CAD vs. No CAD: adjusted hazard ratio (adj-HR) 2.86 (95% confidence interval [CI] 1.14-7.17, p=0.025); clinical CAD vs. No CAD: adj-HR 3.74 (95% CI 1.21-11.60, p=0.022). Among patients with subclinical CAD, increasing CAC burden was associated with higher rates of in-hospital mortality (20.5% vs. 27.9% vs. 38.7% for patients with CAC score thresholds≤100, 101-400 and > 400, respectively, p < 0.001). The adj-HR per 50 points increase in CAC score 1.007 (95%CI 1.001-1.013, p=0.016). Cardiovascular risk factors were not independent predictors of in-hospital mortality when CAD presence and extent were taken into account. CONCLUSIONS: The presence and extent of CAD are associated with in-hospital mortality and MI/CVA among hospitalized patients with COVID-19 disease and they appear to be a better prognostic gauge as compared to a clinical cardiovascular risk assessment.

Coronary and total thoracic calcium scores predict mortality and provides pathophysiologic insights in COVID-19 patients.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has spread worldwide determining dramatic impacts on healthcare systems. Early identification of high-risk parameters is required in order to provide the best therapeutic approach. Coronary, thoracic aorta and aortic valve calcium can be measured from a non-gated chest computer tomography (CT) and are validated predictors of cardiovascular events and all-cause mortality. However, their prognostic role in acute systemic inflammatory diseases, such as COVID-19, has not been investigated. OBJECTIVES: The aim was to evaluate the association of coronary artery calcium and total thoracic calcium on in-hospital mortality in COVID-19 patients. METHODS: 1093 consecutive patients from 16 Italian hospitals with a positive swab for COVID-19 and an admission chest CT for pneumonia severity assessment were included. At CT, coronary, aortic valve and thoracic aorta calcium were qualitatively and quantitatively evaluated separately and combined together (total thoracic calcium) by a central Core-lab blinded to patients' outcomes. RESULTS: Non-survivors compared to survivors had higher coronary artery [Agatston (467.76 â€‹± â€‹570.92 vs 206.80 â€‹± â€‹424.13 â€‹mm2, p â€‹< â€‹0.001); Volume (487.79 â€‹± â€‹565.34 vs 207.77 â€‹± â€‹406.81, p â€‹< â€‹0.001)], aortic valve [Volume (322.45 â€‹± â€‹390.90 vs 98.27 â€‹± â€‹250.74 mm2, p â€‹< â€‹0.001; Agatston 337.38 â€‹± â€‹414.97 vs 111.70 â€‹± â€‹282.15, p â€‹< â€‹0.001)] and thoracic aorta [Volume (3786.71 â€‹± â€‹4225.57 vs 1487.63 â€‹± â€‹2973.19 mm2, p â€‹< â€‹0.001); Agatston (4688.82 â€‹± â€‹5363.72 vs 1834.90 â€‹± â€‹3761.25, p â€‹< â€‹0.001)] calcium values. Coronary artery calcium (HR 1.308; 95% CI, 1.046-1.637, p â€‹= â€‹0.019) and total thoracic calcium (HR 1.975; 95% CI, 1.200-3.251, p â€‹= â€‹0.007) resulted to be independent predictors of in-hospital mortality. CONCLUSION: Coronary, aortic valve and thoracic aortic calcium assessment on admission non-gated CT permits to stratify the COVID-19 patients in-hospital mortality risk.

Chest CT-derived pulmonary artery enlargement at the admission predicts overall survival in COVID-19 patients: insight from 1461 consecutive patients in Italy.

OBJECTIVES: Enlarged main pulmonary artery diameter (MPAD) resulted to be associated with pulmonary hypertension and mortality in a non-COVID-19 setting. The aim was to investigate and validate the association between MPAD enlargement and overall survival in COVID-19 patients. METHODS: This is a cohort study on 1469 consecutive COVID-19 patients submitted to chest CT within 72 h from admission in seven tertiary level hospitals in Northern Italy, between March 1 and April 20, 2020. Derivation cohort (n = 761) included patients from the first three participating hospitals; validation cohort (n = 633) included patients from the remaining hospitals. CT images were centrally analyzed in a core-lab blinded to clinical data. The prognostic value of MPAD on overall survival was evaluated at adjusted and multivariable Cox's regression analysis on the derivation cohort. The final multivariable model was tested on the validation cohort. RESULTS: In the derivation cohort, the median age was 69 (IQR, 58-77) years and 537 (70.6%) were males. In the validation cohort, the median age was 69 (IQR, 59-77) years with 421 (66.5%) males. Enlarged MPAD (≥ 31 mm) was a predictor of mortality at adjusted (hazard ratio, HR [95%CI]: 1.741 [1.253-2.418], p < 0.001) and multivariable regression analysis (HR [95%CI]: 1.592 [1.154-2.196], p = 0.005), together with male gender, old age, high creatinine, low well-aerated lung volume, and high pneumonia extension (c-index [95%CI] = 0.826 [0.796-0.851]). Model discrimination was confirmed on the validation cohort (c-index [95%CI] = 0.789 [0.758-0.823]), also using CT measurements from a second reader (c-index [95%CI] = 0.790 [0.753;0.825]). CONCLUSION: Enlarged MPAD (≥ 31 mm) at admitting chest CT is an independent predictor of mortality in COVID-19. KEY POINTS: • Enlargement of main pulmonary artery diameter at chest CT performed within 72 h from the admission was associated with a higher rate of in-hospital mortality in COVID-19 patients. • Enlargement of main pulmonary artery diameter (≥ 31 mm) was an independent predictor of death in COVID-19 patients at adjusted and multivariable regression analysis. • The combined evaluation of clinical findings, lung CT features, and main pulmonary artery diameter may be useful for risk stratification in COVID-19 patients.

Effect of empagliflozin on brachial artery shear stress and endothelial function in subjects with type 2 diabetes: Results from an exploratory study.

Empagliflozin reduces the risk of cardiovascular mortality in subjects with type 2 diabetes. We demonstrated that empagliflozin increases blood viscosity and carotid shear stress and decreases carotid wall thickness. Shear stress is the force acting on the endothelial surface and modulates arterial function. The current study evaluates the influence of empagliflozin on brachial artery shear stress and endothelial function compared to incretin-based therapy. The study is a nonrandomized, open, prospective cohort study including 35 subjects with type 2 diabetes administered empagliflozin or incretin-based therapy. Shear stress was calculated with a validated formula, and endothelial function was evaluated using the flow-mediated dilation technique. Both treatments resulted in comparable reductions in blood glucose and glycated haemoglobin. Brachial artery shear stress significantly increased exclusively in the empagliflozin group (61 ± 20 vs 68 ± 25 dynes/cm2, p = 0.04), whereas no significant difference was detected in the incretin-based therapy group (60 ± 20 vs 55 ± 12 dynes/cm2, p = not significant). Flow-mediated dilation significantly increased in the empagliflozin group (4.8 ± 4.5% vs 8.5 ± 5.6%, p = 0.03). Again, no change was detected in the incretin-based therapy group (5.1 ± 4.5% vs 4.7 ± 4.7%, p = not significant). The present findings demonstrate the beneficial effect of empagliflozin on shear stress and endothelial function in subjects with type 2 diabetes independent of the hypoglycaemic effect.