Prognostic Value of Troponins in Acute Pulmonary Embolism

Background— Whether elevated serum troponin levels identify patients with acute pulmonary embolism at high risk of short-term mortality or adverse outcome is undefined. Methods and Results— We performed a meta-analysis of studies in patients with acute pulmonary embolism to assess the prognostic value of elevated troponin levels for short-term death and adverse outcome events (composite of death and any of the following: shock, need for thrombolysis, endotracheal intubation, catecholamine infusion, cardiopulmonary resuscitation, or recurrent pulmonary embolism). Unrestricted searches of MEDLINE and EMBASE bibliographic databases from January 1998 to November 2006 were performed using the terms "troponin" and "pulmonary embolism." Additionally, review articles and bibliographies were manually searched. Cohort studies were included if they had used cardiac-specific troponin assays and had reported on short-term death or adverse outcome events. A random-effects model was used to pool study results; funnel-plot inspection was done to evaluate publication bias; and I 2 testing was used to test for heterogeneity. Data from 20 studies (1985 patients) were included in the analysis. Overall, 122 of 618 patients with elevated troponin levels died (19.7%; 95% confidence interval [CI], 16.6 to 22.8) compared with 51 of 1367 with normal troponin levels (3.7%; 95% CI, 2.7 to 4.7). Elevated troponin levels were significantly associated with short-term mortality (odds ratio [OR], 5.24; 95% CI, 3.28 to 8.38), with death resulting from pulmonary embolism (OR, 9.44; 95% CI, 4.14 to 21.49), and with adverse outcome events (OR, 7.03; 95% CI, 2.42 to 20.43). Elevated troponin levels were associated with a high mortality in the subgroup of hemodynamically stable patients (OR, 5.90; 95% CI, 2.68 to 12.95). Results were consistent for troponin I or T and prospective or retrospective studies. Conclusions— Elevated troponin levels identify patients with acute pulmonary embolism at high risk of short-term death and adverse outcome events

Role of heparin prophylaxis at different doses in patients with COVID-19 and respiratory failure: a systematic review and meta-analysis

Abstract Background Venous thromboembolism (VTE) is common in patients with coronavirus disease-2019 (COVID-19). The use of heparin at higher doses than prophylactic is advocated, but the optimal regimens remain unknown due to the balance between prevention of thromboembolic events and bleeding risks. Objective To systematically review and perform a meta-analysis aimed at evaluating the risk of VTE and of major bleeding (MB) in patients with respiratory failure due to COVID-19 according to heparin doses. Methods We performed a systematic search in MEDLINE up until 22 March 2021. Studies on patients with respiratory failure due to COVID-19 were included if reported on study outcomes according to standard prophylactic and to higher heparin doses and included more than 10 patients. Study primary outcome was VTE; secondary outcomes were MB, all-cause death, fatal bleeding and fatal pulmonary embolism (PE). Results Overall, 2 randomized and 16 observational studies were selected (3458 patients). In 13 studies (2492 patients) VTE events were similar in patients receiving standard prophylaxis or higher heparin doses (RR 1.06, 95% CI 0.58–1.95, I2 87%; only randomized studies RR 1.72, 95% CI 0.78–3.81, I2 54%). 16 studies (3174) reporting on MB and showed a significant reduction in favor of standard heparin prophylaxis (RR 0.39, 95% CI 0.28–0.53, I2 8%). No differences were observed for overall mortality according to heparin doses (RR 1.11, 95% CI 0.88–1.40, I2 68%; in 8 studies, 2448 patients). Similarly, no differences were observed for fatal bleedings and fatal PEs. In the subanalysis of studies reporting only on intensive care unit patients (ICU) an increase in the risk of VTE (RR 1.86, 95% CI 1.28–2.72, I2 18%) and a reduction on the risk of MB (RR 0.60, 95% CI 0.40–0.90, I2 0%) were observed in patients receiving standard heparin doses compared to higher doses. Overall mortality was similar (RR 1.09, 95% CI 0.86–1.39, I2 64%). Conclusion Different doses of heparin prophylaxis seem to not affect the risk of VTE in the overall patients with COVID-19 and respiratory failure. In studies reporting only on ICU patients the risk of VTE was lower when higher heparin doses were used compared to standard doses, but with no advantage in overall death and with an increase of MBs. Funding Acknowledgement Type of funding sources: None

Embolia polmonare in paziente in duplice terapia antipiastrinica per posizionamento di DES

Venous thromboembolism (VTE), including deep vein thrombosis and pulmonary embolism (PE), is the third most frequent cardiovascular disease and is characterized by high mortality and disability rate. According to the 2014 European Society of Cardiology guidelines for the treatment of PE, anticoagulant therapy is recommended in patients with acute PE for a period of at least 3 months in order to prevent both early mortality and recurrence of VTE. To date, there are no studies conducted on the triple antithrombotic therapy in patients with VTE subjected to percutaneous coronary interventions. We report the case of an elderly patient in dual antiplatelet therapy following coronary revascularization and stenting. The patient, following an episode of PE with cardiac arrest after 12 days of hospitalization, was successfully treated with anticoagulant therapy with dabigatran in association with the dual antiplatelet therapy already in place (Cardiology)

DFORM: Diffeomorphic vector field alignment for assessing dynamics across learned models

Dynamical system models such as Recurrent Neural Networks (RNNs) have become increasingly popular as hypothesis-generating tools in scientific research. Evaluating the dynamics in such networks is key to understanding their learned generative mechanisms. However, comparison of learned dynamics across models is challenging due to their inherent nonlinearity and because a priori there is no enforced equivalence of their coordinate systems. Here, we propose the DFORM (Diffeomorphic vector field alignment for comparing dynamics across learned models) framework. DFORM learns a nonlinear coordinate transformation which provides a continuous, maximally one-to-one mapping between the trajectories of learned models, thus approximating a diffeomorphism between them. The mismatch between DFORM-transformed vector fields defines the orbital similarity between two models, thus providing a generalization of the concepts of smooth orbital and topological equivalence. As an example, we apply DFORM to models trained on a canonical neuroscience task, showing that learned dynamics may be functionally similar, despite overt differences in attractor landscapes.Comment: 12 pages, 8 figure

Cerebral venous sinus thrombosis associated with cancer: analysis of the ACTION-CVT study.

Nearly one fifth of patients with venous thromboembolism (VTE) have cancer. When both of these conditions occur, especially in cases of cerebral vein thrombosis (CVT), patient management is often challenging. The aim of this study was to compare the characteristics and event courses in patients affected by CVT with and without cancer. Consecutive patients with CVT from the ACTION-CVT cohort study were included if cancer status was reported. Risk factors as well as the clinical and radiological characteristics of patients were compared. Univariable and multivariable analyses were performed to assess variables associated with cancer. Kaplan-Meier method and log-rank test, logistic regression analysis, and propensity score matching were used to investigate any association between cancer-related CVT and study outcomes (primary outcome at 3-months: recurrent VTE or major hemorrhage; recurrent VTE; major hemorrhage; recanalization status; all-cause-death). Overall, 1,023 patients with CVT were included, of which 6.5% had cancer. Older age (adjusted odds ratio [aOR] 1.28 per decade increase; 95% confidence interval [CI] 1.08-1.52) and absence of headache (aOR 0.47; 95% CI 0.27-0.84) were independently associated with cancer. Patients with cancer had a higher risk of recurrent VTE or major hemorrhage (aOR 3.87; 95% CI 2.09-7.16), all-cause-death (aOR 7.56 95% CI 3.24-17.64), and major hemorrhage (aOR 3.70 95% CI 1.76-7.80). Recanalization rates, partial or complete, was not significantly different. CVT patients with cancer were more likely to be older, have no referred headache, and have worse outcomes compared to CVT patients without cancer

Endothelial dysfunction in patients with spontaneous venous thromboembolism

Background and Objectives A high incidence of atherosclerotic lesions and cardiovascular events has been reported in patients with spontaneous venous thromboembolism. Endothelial dysfunction is an early marker of atherosclerosis and has predictive value for ischemic events. We have evaluated endothelial function in patients with a history of spontaneous venous thromboembolism.Design and Methods Patients with a history of symptomatic, objectively confirmed, spontaneous venous thromboembolism were included in a case-control study. Exclusion criteria were any known risk factors for cardiovascular diseases, other conditions associated with endothelial dysfunction, estro-progestinic therapy or pregnancy. Controls were age-(±5 years) and sex-matched subjects with the same exclusion criteria but without previous venous thromboembolism. Endothelial function was evaluated by the non-invasive measurement of flow-mediated vasodilation of the brachial artery and of plasma markers of endothelium activation; platelet activation parameters were also measured.Results Twenty-eight cases (8 females; mean age 59±15 years) and 28 controls (8 females; mean age 58±15) were studied. Flow-mediated vasodilation was 3.5±0.6% in cases (95% CIs: 2.2 to 4.8) and 5.7±0.6% (4.2 to 6.8) in controls (p=0.015). Brachial artery blood flow and hyperemic blood flow did not differ between the two groups. Plasma von Willebrand factor and soluble P-selectin levels were significantly higher in patients with venous thromboembolism, while plasma soluble CD40 ligand and urinary 11-dehydro-TxB2 levels were similar in cases and controls.Interpretation and Conclusions Patients with spontaneous venous thromboembolism have endothelial dysfunction, unlike age- and sex- matched controls. This finding suggests that spontaneous venous thromboembolism may be a condition associated with an enhanced risk of atherosclerosis

Timing and Predictors of Recanalization After Anticoagulation in Cerebral Venous Thrombosis.

BACKGROUND AND PURPOSE Vessel recanalization after cerebral venous thrombosis (CVT) is associated with favorable outcomes and lower mortality. Several studies examined the timing and predictors of recanalization after CVT with mixed results. We aimed to investigate predictors and timing of recanalization after CVT. METHODS We used data from the multicenter, international AntiCoagulaTION in the Treatment of Cerebral Venous Thrombosis (ACTION-CVT) study of consecutive patients with CVT from January 2015 to December 2020. Our analysis included patients that had undergone repeat venous neuroimaging more than 30 days after initiation of anticoagulation treatment. Prespecified variables were included in univariate and multivariable analyses to identify independent predictors of failure to recanalize. RESULTS Among the 551 patients (mean age, 44.4±16.2 years, 66.2% women) that met inclusion criteria, 486 (88.2%) had complete or partial, and 65 (11.8%) had no recanalization. The median time to first follow-up imaging study was 110 days (interquartile range, 60-187). In multivariable analysis, older age (odds ratio [OR], 1.05; 95% confidence interval [CI], 1.03-1.07), male sex (OR, 0.44; 95% CI, 0.24-0.80), and lack of parenchymal changes on baseline imaging (OR, 0.53; 95% CI, 0.29-0.96) were associated with no recanalization. The majority of improvement in recanalization (71.1%) occurred before 3 months from initial diagnosis. A high percentage of complete recanalization (59.0%) took place within the first 3 months after CVT diagnosis. CONCLUSION Older age, male sex, and lack of parenchymal changes were associated with no recanalization after CVT. The majority recanalization occurred early in the disease course suggesting limited further recanalization with anticoagulation beyond 3 months. Large prospective studies are needed to confirm our findings

Outcome Prediction in Cerebral Venous Thrombosis: The IN-REvASC Score.

BACKGROUND We identified risk factors, derived and validated a prognostic score for poor neurological outcome and death for use in cerebral venous thrombosis (CVT). METHODS We performed an international multicenter retrospective study including consecutive patients with CVT from January 2015 to December 2020. Demographic, clinical, and radiographic characteristics were collected. Univariable and multivariable logistic regressions were conducted to determine risk factors for poor outcome, mRS 3-6. A prognostic score was derived and validated. RESULTS A total of 1,025 patients were analyzed with median 375 days (interquartile range [IQR], 180 to 747) of follow-up. The median age was 44 (IQR, 32 to 58) and 62.7% were female. Multivariable analysis revealed the following factors were associated with poor outcome at 90- day follow-up: active cancer (odds ratio [OR], 11.20; 95% confidence interval [CI], 4.62 to 27.14; P<0.001), age (OR, 1.02 per year; 95% CI, 1.00 to 1.04; P=0.039), Black race (OR, 2.17; 95% CI, 1.10 to 4.27; P=0.025), encephalopathy or coma on presentation (OR, 2.71; 95% CI, 1.39 to 5.30; P=0.004), decreased hemoglobin (OR, 1.16 per g/dL; 95% CI, 1.03 to 1.31; P=0.014), higher NIHSS on presentation (OR, 1.07 per point; 95% CI, 1.02 to 1.11; P=0.002), and substance use (OR, 2.34; 95% CI, 1.16 to 4.71; P=0.017). The derived IN-REvASC score outperformed ISCVT-RS for the prediction of poor outcome at 90-day follow-up (area under the curve [AUC], 0.84 [95% CI, 0.79 to 0.87] vs. AUC, 0.71 [95% CI, 0.66 to 0.76], χ2 P<0.001) and mortality (AUC, 0.84 [95% CI, 0.78 to 0.90] vs. AUC, 0.72 [95% CI, 0.66 to 0.79], χ2 P=0.03). CONCLUSIONS Seven factors were associated with poor neurological outcome following CVT. The INREvASC score increased prognostic accuracy compared to ISCVT-RS. Determining patients at highest risk of poor outcome in CVT could help in clinical decision making and identify patients for targeted therapy in future clinical trials