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Background/Objectives: Although SARS-CoV-2 infection is a significant risk factor for venous thromboembolism (VTE), data on the impact of the use of non-invasive ventilation support (NIVS) to mitigate the risk of VTE during hospitalization are scarce. Methods: Data for 1471 SARS-CoV-2 patients, hospitalized in a single hub during the first pandemic wave, were collected from clinical records, including symptom duration and type, information on lung abnormalities on chest computed tomography (CT), laboratory parameters and the use of NIVS. Determining VTE occurrence during hospital stays was the main endpoint. Results: Patients with VTE (1.8%) had an increased prevalence of obesity (26% vs. 11%), diabetes (41% vs. 21%), higher CHA2DS2VASC score (4, IQR 2–5 vs. 3, IQR 1–4, age- and sex-adjusted, p = 0.021) and cough (65% vs. 44%) and experienced significantly higher rates of NIVS (44% vs. 8%). Using a stepwise multivariate logistic regression model, the prevalence of electrocardiogram abnormalities (odds ratio (OR) 2.722, 95% confidence interval (CI) 1.039–7.133, p = 0.042), cough (OR 3.019, 95% CI 1.265–7.202, p = 0.013), CHA2DS2-VASC score > 3 (OR 3.404, 95% CI 1.362–8.513, p = 0.009) and the use of NIVS (OR 15.530, 95% CI 6.244–38.627, p < 0.001) were independently associated with a risk of VTE during hospitalization. NIVS remained an independent risk factor for VTE even after adjustment for the period of admission within the pandemic wave. Conclusions: Our study suggests that NIVS is a risk factor for VTE during hospitalization in SARS-CoV-2 patients. Future studies should assess the optimal prophylactic strategy against VTE in patients with a SARS-CoV-2 infection candidate to non-invasive ventilatory support. [ABSTRACT FROM AUTHOR]

The association between statin use and mortality in patients with deep vein thrombosis (DVT) has not been rigorously evaluated. We used the data in the RIETE registry to examine the association between statin use and mortality at 3 months. We used mixed effects survival models accounting for clinical covariates and clustering of patients in enrolling centers. From January 2009 through April 2022, there were 46,440 patients with isolated DVT in RIETE (in the lower-limbs 42,291, in the upper limbs 4149). Of these, 21 % and 18 %, respectively, were using statins. Statin users were older than non-users (72 ± 12 vs. 62 ± 18 years), and more likely had diabetes, hypertension, prior myocardial infarction or ischemic stroke, or were receiving antiplatelets. The 3-month mortality rates were: 6.0 % vs. 5.8 %, respectively. On multilevel multivariable analysis, the adjusted hazard ratio (aHR) for all-cause death in statin users vs. non-users was 0.77 (95%CI: 0.69–0.86). The 3-month risk of death in statin users was significantly lower than in non-users in patients with upper-limb DVT (aHR: 0.81; 95%CI: 0.72–0.91), distal lower-limb DVT (aHR: 0.48; 95%CI: 0.32–0.72), or proximal lower-limb DVT (aHR: 0.69; 95%CI: 0.50–0.95), and in those receiving simvastatin (aHR: 0.73; 95%CI: 0.60–0.90), atorvastatin (aHR: 0.70; 95%CI: 0.59–0.85), or rosuvastatin (aHR: 0.47; 95%CI: 0.27–0.80). Major bleeding, used as a falsification endpoint, did not show an association with use of statins at 3-month follow-up. Statin users with isolated DVT were at significantly lower risk for death at 3 months than non-users. • Statins possess antithrombotic and profibrinolytic properties • We compare the 3 months all-cause mortality in patients with DVT according to the use of statins • Statin users with isolated DVT were at lower adjusted risk for death at 3 months • Randomized trials are needed to confirm these data [ABSTRACT FROM AUTHOR]

Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by thrombotic or obstetric events occurring in individuals who have persistent antiphospholipid antibodies. Catastrophic antiphospholipid syndrome (CAPS) is a rare and potentially fatal form of APS characterized by severe thrombotic complications occurring in multiple organs over a short period of time or simultaneously. CAPS is associated with a high (50%) death rate. Infections, multi-organ failure, and cerebral and heart thrombosis represent the main complications of this syndrome. Generally, anticoagulants, glucocorticoids, therapeutic plasmapheresis (TPE), and intravenous immunoglobulin (IVIG) are used in combination for treatment. Multidisciplinary care involving different specialists from hematology, rheumatology, nephrology, infectious disease, critical care, and obstetrics is often required due to the complexity of the disease. Recent data emphasize the effectiveness of biologics such as anti-TNF-a monoclonal antibodies (adalimumab, certolizumab), anti-CD38 monoclonal antibody (daratumumab), BAFF/Blys inhibitor (belimumab), and BTK inhibitor (zanubrutinib) against CAPS. In order to understand the underlying causes of CAPS, one future possibility involves investigating and characterizing the hereditary and acquired risk factors associated with CAPS. [ABSTRACT FROM AUTHOR]

Statins are powerful lipid-lowering drugs that inhibit cholesterol biosynthesis via downregulation of hydroxymethylglutaryl coenzyme-A reductase, which are largely used in patients with or at risk of cardiovascular disease. Available data on thromboembolic disease include primary and secondary prevention as well as bleeding and mortality rates in statin users during anticoagulation for VTE. Experimental studies indicate that statins alter blood clotting at various levels. Statins produce anticoagulant effects via downregulation of tissue factor expression and enhanced endothelial thrombomodulin expression resulting in reduced thrombin generation. Statins impair fibrinogen cleavage and reduce thrombin generation. A reduction of factor V and factor XIII activation has been observed in patients treated with statins. It is postulated that the mechanisms involved are downregulation of factor V and activated factor V, modulation of the protein C pathway and alteration of the tissue factor pathway inhibitor. Clinical and experimental studies have shown that statins exert antiplatelet effects through early and delayed inhibition of platelet activation, adhesion and aggregation. It has been postulated that statin-induced anticoagulant effects can explain, at least partially, a reduction in primary and secondary VTE and death. Evidence supporting the use of statins for prevention of arterial thrombosis-related cardiovascular events is robust, but their role in VTE remains to be further elucidated. In this review, we present biological evidence and experimental data supporting the ability of statins to directly interfere with the clotting system. [ABSTRACT FROM AUTHOR]

Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by thrombotic or obstetric events occurring in patients with persistent antiphospholipid antibodies. Thrombotic APS is characterized by venous, arterial, or microvascular thrombosis. The diagnosis is accepted when both one clinical and one laboratory criteria according to the updated Sapporo classification are established. APS may occur in combination with other autoimmune diseases, mainly systemic lupus erythematosus, or in its primary form. Long-term anticoagulation with a vitamin K antagonist is the standard of care for patients who develop thrombosis, considering the high rate of recurrent thrombosis. The current international guidelines are not in favor of recommending direct oral anticoagulants for secondary prevention of thrombotic antiphospholipid syndrome, especially in the context of arterial thrombosis and triple-positive antiphospholipid patients. The most common approach, endorsed by the American College of Chest Physicians guidelines is the combination of heparin and low-dose aspirin (75-100 mg) daily for women who fulfill the clinical and serologic criteria for obstetric APS. New potential therapeutic approaches are under evaluation but actually the anticoagulation remains the cornerstone of treatment. [ABSTRACT FROM AUTHOR]

Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by thrombotic or obstetric events occurring in patients with persistent antiphospholipid antibodies. Thrombotic APS is characterized by venous, arterial, or microvascular thrombosis. The diagnosis is accepted when both one clinical and one laboratory criteria according to the updated Sapporo classification are established. APS may occur in combination with other autoimmune diseases, mainly systemic lupus erythematosus, or in its primary form. Long-term anticoagulation with a vitamin K antagonist is the standard of care for patients who develop thrombosis, considering the high rate of recurrent thrombosis. The current international guidelines are not in favor of recommending direct oral anticoagulants for secondary prevention of thrombotic antiphospholipid syndrome, especially in the context of arterial thrombosis and triple-positive antiphospholipid patients. The most common approach, endorsed by the American College of Chest Physicians guidelines is the combination of heparin and low-dose aspirin (75-100 mg) daily for women who fulfill the clinical and serologic criteria for obstetric APS. New potential therapeutic approaches are under evaluation but actually the anticoagulation remains the cornerstone of treatment. [ABSTRACT FROM AUTHOR]

Background/Objectives: Older patients are subject to a high number of Emergency Department (ED) visits and hospitalizations. Innovative strategies to manage geriatric urgencies in the community are thus needed. Methods: In this prospective observational study, we examined the case mix of a hospital-based domiciliary urgent care service tailored to older patients, called Multidisciplinary Mobile Unit (MMU), from January to September 2023. The service, activated by general practitioners or territorial specialists during workdays, provided domiciliary geriatric assessment, point-of-care diagnostics, including multi-site ultrasound and lab tests, and therapeutical measures, including intravenous treatment and insertion of invasive devices, with the goal of reaching on-site stabilization and avoiding ED referral. We collected data regarding multimorbidity, polypharmacy, and frailty according to the Clinical Frailty Scale (CFS), reasons for MMU activation, and diagnostic and therapeutical services provided. The assessed outcomes were immediate hospitalization after a visit, 30-day admission, and 30-day mortality. Results: Participants (n = 205, 102 M) were mostly aged (median age 83 years old), with multimorbidity and frailty (CFS median 6). The most frequent reasons for MMU activation were dyspnea (49%), cough (34%), and musculoskeletal pain (17%), while the commonest diagnostic test provided was thoracic ultrasound (81%). Only five patients (2.4%) were hospitalized immediately after MMU visit. The 30-day rate of hospitalization was 10.2%, with age, cancer, and abdominal pain as independent predictors on a stepwise binary logistic regression model. 30-day mortality was 4.9%. Conclusions: The MMU model is a feasible strategy to manage geriatric urgencies, especially involving the cardiorespiratory system, is associated with good outcomes and may prevent ED visits. [ABSTRACT FROM AUTHOR]

The clinical outcomes during the course of anticoagulation in patients with venous thromboembolism (VTE) using statins remain controversial. We used the RIETE (Registro Informatizado Enfermedad TromboEmbólica) registry to compare the risk for VTE recurrences, major bleeding or death during anticoagulation, according to the use of statins at baseline. We used propensity score-matching (PSM) to adjust for confounding variables. From February 2009 to January 2018, 32,062 VTE patients were included. Of these, 7,085 (22%) were using statins. Statin users were 10 years older (73±11 vs. 63±19 years, respectively) and more likely to have comorbidities or to be using antiplatelets or corticosteroids at baseline than non-users. During the course of anticoagulation (median, 177 days), 694 patients developed VTE recurrences, 848 bled and 3,169 died (fatal pulmonary embolism 176, fatal bleeding 121). Statin users had a similar rate of VTE recurrences (hazard ratio [HR]: 0.98; 95%CI: 0.82–1.17), a higher rate of major bleeding (HR: 1.29; 95%CI: 1.11–1.50) and a similar mortality rate (HR: 1.01; 95%CI: 0.93–1.10) than non-users. On PSM analysis, statin users had a significantly lower risk for death (HR: 0.62; 95%CI: 0.48–0.79) and a similar risk for VTE recurrences (HR: 0.98; 95%CI: 0.61–1.57) or major bleeding (HR: 0.85; 95%CI: 0.59–1.21) than non-users. During anticoagulation for VTE, patients using statins at baseline had a lower risk to die than non-users. • In venous thromboembolism, statin users had a lower risk to die than non-users. • The rate of venous thromboembolism recurrences is similar in the two groups. • The rate of major bleeding is similar in the two groups. • Intervention studies specifically designed to confirm these findings are warranted. [ABSTRACT FROM AUTHOR]

Highlights • A multitude of athletes use to practice alone in the countryside where an exercise-associated cardiac arrest is typically not witnessed. • The Heart Sentinel ™ app (HS-app) is conceived to detect cardiac arrest during outdoor sports, automatically alerting contacts via SMS with GPS position data. • A simple smartphone app, using commercially-available heart rate monitors, is promising to detect cardiac arrest caused by VF during sports. [ABSTRACT FROM AUTHOR]

Background: Stress testing in patients with low pretest probability (PTP) of coronary artery disease (CAD) has become an increasing practice, potentially leading to underestimation of its true clinical value. Our aim was to describe the current use of most employed imaging functional tests and their prognostic value. Methods and Results: We selected patients with low PTP of CAD (CAD consortium clinical score < 15%) who underwent exercise or dipyridamole stress echocardiography or single photon emission computed tomography for suspected angina. Main exclusions were age < 45, known CAD, and abnormal rest wall motion. Of the 2279 subjects undergoing stress test, 883 (39%) had low PTP, and 91 (10.3%) had a positive test for ischemia. After a median follow‐up of 5.8 years, 36 patients had events (21 died, 14 had nonfatal myocardial infarction). The percentage of events in the abnormal and normal stress test groups were similar (5 [5.5%] vs 31 [3.9%], P = ns), as the annualized event rate (0.87% vs 0.62%, P = ns). Age was the only variable associated with outcome in the regression analysis (hazard ratio 1.072, 95% CI 1.034–1.113, P < 0.001). An abnormal result was not associated with worse outcome in each of the subgroups of functional tests. Conclusions: In our geographical area, a considerable proportion of patients undergoing imaging functional tests for stable chest pain have a low estimated PTP of CAD. Of these, 1 in 10 resulted positive for inducible ischemia. However, none of the most common imaging functional tests, single photon emission computed tomography (SPECT), and stress echocardiography offer prognostic information in these patients. [ABSTRACT FROM AUTHOR]

Venous thromboembolism (VTE) is common in patients with coronavirus disease-2019 (COVID-19). However, limited data exist on patient characteristics, treatments, and outcomes. To describe the clinical characteristics, treatment patterns, and short-term outcomes of patients diagnosed with VTE during hospitalization for COVID-19. This is a prospective multinational study of patients with incident VTE during the course of hospitalization for COVID-19. Data were obtained from the Registro Informatizado de la Enfermedad TromboEmbólica (RIETE) registry. All-cause mortality, VTE recurrences, and major bleeding during the first 10 days were separately investigated for patients in hospital wards versus those in intensive care units (ICUs). As of May 03, 2020, a total number of 455 patients were diagnosed with VTE (83% pulmonary embolism, 17% isolated deep vein thrombosis) during their hospital stay; 71% were male, the median age was 65 (interquartile range, 55–74) years. Most patients (68%) were hospitalized in medical wards, and 145 in ICUs. Three hundred and seventeen (88%; 95% confidence interval [CI]: 84–91%) patients were receiving thromboprophylaxis at the time of VTE diagnosis. Most patients (88%) received therapeutic low-molecular-weight heparin, and 15 (3.6%) received reperfusion therapies. Among 420 patients with complete 10-day follow-up, 51 (12%; 95% CI: 9.3–15%) died, no patient recurred, and 12 (2.9%; 95% CI: 1.6–4.8%) experienced major bleeding. The 10-day mortality rate was 9.1% (95% CI: 6.1–13%) among patients in hospital wards and 19% (95% CI: 13–26%) among those in ICUs. This study provides characteristics and early outcomes of patients diagnosed with acute VTE during hospitalization for COVID-19. Additional studies are needed to identify the optimal strategies to prevent VTE and to mitigate adverse outcomes associated. [ABSTRACT FROM AUTHOR]

To determine whether calcifications of the coronary arteries (coronary artery calcium 0 to 4 score), or extending the assessment also to cardiac valves and thoracic aorta (overall calcium 0 to 8 score), as seen on computed tomography for attenuation correction during stress-scintigraphy (SPECT-CT), are associated with total mortality and non-fatal myocardial infarction. We aimed to assess whether these calcifications added to the prognostic value of SPECT imaging. The presence/amount of calcium in the coronary arteries, but also in the heart valves and aorta, has been associated with cardiovascular (CV) and all-cause mortality. This information can be obtained during SPECT-CT examinations, where low resolution CT images are co-registered for attenuation correction of myocardial perfusion, but then discarded. Clinical data were collected on 353 consecutive patients submitted to stress SPECT-CT between Sept 2010 and Oct 2012, for suspected coronary artery disease (CAD). Follow-up data on outcomes were collected retrospectively. Mean age was 72 and 58% were male. Mean follow-up was 6.4 years, during which 48 subjects died (15 from CV causes) and 10 had non-fatal myocardial infarction (MI). Reversible perfusion defects were detected in 55 patients (15.6%), 39 of whom (11%) had >mild defects. The presence of a calcium score > 1 in the attenuation correction images was the strongest univariate predictor of all-cause death or MI (hazard ratio 7.21, p <.001). On multivariate analysis, controlling for age, gender and myocardial perfusion defects an overall calcium score > 2 remained a predictor of all-cause death or non-fatal MI (hazard ratio 4.12, p <.001). Visual assessment of coronary or overall coronary, cardiac and aortic calcium in the CT images used for attenuation correction during SPECT-CT is feasible and reproducible. It was strongly associated with all-cause death and MI, even after controlling for clinical variables and myocardial perfusion data. This simple visual calcium assessment does not add additional costs or radiation, and may significantly improve risk-assessment of patients with suspected CAD undergoing SPECT-CT. Calcium in the coronary arteries, heart valves and aorta has been associated with worse prognosis. We sought to determine whether assessment of such calcifications on computed tomography images (co-registered for myocardial perfusion attenuation correction and then discarded) are independently associated with long-term outcome on top of available data. We enrolled 353 consecutive patients, referred for suspected coronary artery disease. An overall calcium score > 1 in the attenuation correction images was the strongest univariate (hazard ratio 7.21, p <.001) and multivariate predictor of all-cause death or non-fatal MI (hazard ratio 4.12, p <.001), even after controlling for clinical variables and myocardial perfusion data. • Stress SPECT is used mainly to demonstrate reversible myocardial perfusion defects. • Coronary and cardiac calcium has been associated with worse prognosis. • In SPECT-CT, CT imaging data used for attenuation correction are usually discarded. • We enrolled 353 patients evaluating perfusion data and coronary and cardiac calcium. • A calcium score > 2 was the strongest predictor of death or myocardial infarction. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to longitudinally evaluate maternal echocardiographic findings in uncomplicated twin gestations according to chorionicity.Methods: Healthy women with twin pregnancy were assessed with transthoracic echocardiography across the first, second, and third trimesters. Cardiac findings were compared within each group and between monochorionic (MC) and dicho-rionic (DC) pregnancies.Results: Overall, 19 MC and 48 DC uncomplicated twin pregnancies were included. In the MC group, no significant maternal haemodynamic changes were documented across gestation, with the exception of a decrease in ejection fraction. Compared to DC pregnancies, in the MC set lower cardiac output (second and third trimester, p = 0.001 and p = 0.006, respectively) and higher total vascular resistance (first trimester, p = 0.032) were observed. Regarding the diastolic function in MC twins, significantly higher values were observed for mitral E/A ratio (third trimester, p = 0.014), septal mitral E1/A1 ratio (third trimester, p = 0.030), lateral mitral E1 (second and third trimester, p = 0.014 and p = 0.029, respectively), and E1/A1 ratio (third trimester, p = 0.006).Conclusions: Maternal cardiac adaptation in twin pregnancy seems to differ significantly according to chorionicity. In particular, in MC pregnancies the impairment of diastolic function is less pronounced, presumably due to the lower circulating volume. [ABSTRACT FROM AUTHOR]

Abstract Background We assessed whether the non-invasive measure of peak diastolic-systolic velocity ratio (rDSVR) at rest on the left anterior descending artery (LAD) using Doppler transthoracic echocardiography is associated with obstructive coronary artery disease (CAD) on the LAD and left main (LM) arteries. We compared rDSVR diagnostic accuracy with stress wall motion (WM) and coronary flow reserve (CFR-LAD), in a group of subjects who underwent contrast stress-echocardiography (cSE) and coronary angiography within 3 months. Methods 286 patients selected with a clinical indication to cSE, in which CFR-LAD was measured during the test who also underwent coronary angiography within 3 months were selected and diagnostic performance compared. Results Demographics and clinical variables were univariate predictors of LAD or LM >50% stenosis, but rDSVR < 1.7 outperformed other variables (OR 11.18, 95% CI 5.82–21.49, p < 0.001), comprising cSE variables such as reversible WM abnormalities (OR 1.53, 95% CI 0.94–2.49, p = 0.087) or CFR-LAD < 2 (OR 2.88, 95% CI 21.74–4.77, p < 0.001). The addition of rDSVR to multivariate logistic regression models (clinical or clinical + cSE variables) led to a marked increase in C-index (0.82, 95%CI 0.78–0.87) with significant improvement compared to all prior models (p < 0.001). Conclusions Our data suggest a strict association of reduced rDSVR with >50% coronary artery stenosis on the LM/LAD, superior to other standard clinical or cSE related indexes, such as WM assessment or CFR-LAD, and builds incrementally to them and clinical variables in multivariable logistic models for the prediction of CAD on LM and LAD coronaries. Highlights • The study suggests a strict association between rest Doppler diastolic-systolic coronary flow velocity ratio (rDSVR) and coronary artery stenosis • This association is significantly higher compared with other standard clinical and also stress-echo indexes • rDSVR builds incrementally to stress-echo and clinical variables in models for the prediction of obstructive CAD on left Main and/or LAD coronary arteries [ABSTRACT FROM AUTHOR]

Background: Venous thromboembolism (VTE)—including deep vein thrombosis, pulmonary embolism, and cerebral venous sinus thrombosis (CVST)—may occur early after vaccination against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We sought to describe the site, clinical characteristics, and outcomes of VTE after vaccination against SARS-CoV-2. Methods: In a prospective study using the Registro Informatizado de Enfermedad TromboEmbólica (RIETE) platform, patients with VTE 4–30 days after vaccination against SARS-CoV-2 (1 February 2021 through 30 April 2021) were included. VTE patients recruited from the same centers into RIETE in the same months in 2018–2019 were selected as the reference group. All-cause mortality and major bleeding were the main study outcomes. Results: As of 30 April 2020, 102 patients with post-vaccination VTEs had been identified (28 after adenovirus-based vaccination [ChAdOx1 nCov-19; AstraZeneca] and 74 after mRNA-based vaccination [mRNA-1273; Moderna, and BNT162b2; Pfizer]). Compared with 911 historical controls, patients with VTE after adenovirus-based vaccination more frequently had CVST (10.7% vs. 0.4%, p < 0.001) or thrombosis at multiple sites (17.9% vs. 1.3%, p < 0.001), more frequently had thrombocytopenia (40.7% vs. 14.7%, p < 0.001), and had higher 14-day mortality (14.3% vs. 0.7%; odds ratio [OR]: 25.1; 95% confidence interval [CI]: 6.7–94.9) and major bleeding rates (10.3% vs. 1.0%, OR: 12.03, 95% CI: 3.07–47.13). The site of thrombosis, accompanying thrombocytopenia, and 14-day mortality rates were not significantly different for patients with VTE after mRNA-based vaccination, compared with historical controls. Conclusions: Compared with historical controls, VTE after adenovirus-based vaccination against SARS-CoV-2 is accompanied by thrombocytopenia, occurs in unusual sites, and is associated with worse clinical outcomes. [ABSTRACT FROM AUTHOR]