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)

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

Complex clinical scenarios with the use of direct oral anticoagulants in patients with atrial fibrillation:a multidisciplinary expert advisory board

The risk of developing atrial fibrillation (AF) and the risk of stroke both increase with advancing age. As such, many individuals have, or will develop, an indication for oral anticoagulation to reduce the risk of stroke. Currently, a large number of anticoagulants are available, including vitamin K antagonists, direct thrombin or factor Xa inhibitors (the last two also referred to as direct oral anticoagulants or DOACs), and different dosages are available. Of the DOACs, rivaroxaban can be obtained in the most different doses: 2.5mg, 5mg, 15mg and 20mg. Many patients develop co-morbidities and/or undergo procedures that may require the temporary combination of anticoagulation with antiplatelet therapy. In daily practice, clinicians encounter complex scenarios that are not always described in the treatment guidelines, and clear recommendations are lacking. Here, we report the outcomes of a multidisciplinary advisory board meeting, held in Utrecht (The Netherlands) on 3 June 2019, on decision making in complex clinical situations regarding the use of DOACs. The advisory board consisted of Dutch cardiovascular specialists: (interventional) cardiologist, internist, neurologist, vascular surgeon and general practitioners invited according to personal title and specific field of expertise

Can a Trained Radiology Technician Do Arterial Obstruction Quantification in Patients With Acute Pulmonary Embolism?

Objectives: To assess interobserver variability between a trained radiology technician (RT) and an experienced radiologist in arterial obstruction quantification using the Qanadli obstruction index (QOI), in patients diagnosed with acute pulmonary embolism (APE) at CT pulmonary angiography (CTPA). Materials and Methods: A RT and a radiologist independently reviewed CTPAs of 97 consecutive, prospectively enrolled patients with APE, and calculated the QOI. They classified patients into three risk categories: high for QOI ≥40%, intermediate for QOI 20-37.5%, low for QOI &lt;20%. Interobserver variability was investigated for QOI as a continuous variable and as a categorical variable (high, intermediate, and low-risk groups). Results: Mean QOI (±SD) was 39.5 ± 24.3% and 38.6 ± 18.9% for the RT and the radiologist, respectively. The mean QOI was not statistically different between the RT and the radiologist (p = 0.502), and the interobserver agreement was excellent (ICC = 0.905). The RT classified 54 patients (55.7%) as high, 17 (17.53%) as intermediate, and 26 (26.8%) as low risk. The radiologist classified 55 patients (56.7%) as high, 22 (22.7%) as intermediate, and 20 (20.6%) as low risk. The interrater agreement for risk stratification was excellent (weighted kappa = 0.844). Conclusion: Once the diagnosis of APE was established, an adequately trained RT achieved an accuracy comparable to that of an experienced radiologist regarding QOI calculation and risk assessment

Frequency of left ventricular hypertrophy in non-valvular atrial fibrillation

Left ventricular hypertrophy (LVH) is significantly related to adverse clinical outcomes in patients at high risk of cardiovascular events. In patients with atrial fibrillation (AF), data on LVH, that is, prevalence and determinants, are inconsistent mainly because of different definitions and heterogeneity of study populations. We determined echocardiographic-based LVH prevalence and clinical factors independently associated with its development in a prospective cohort of patients with non-valvular (NV) AF. From the "Atrial Fibrillation Registry for Ankle-brachial Index Prevalence Assessment: Collaborative Italian Study" (ARAPACIS) population, 1,184 patients with NVAF (mean age 72 \ub1 11 years; 56% men) with complete data to define LVH were selected. ARAPACIS is a multicenter, observational, prospective, longitudinal on-going study designed to estimate prevalence of peripheral artery disease in patients with NVAF. We found a high prevalence of LVH (52%) in patients with NVAF. Compared to those without LVH, patients with AF with LVH were older and had a higher prevalence of hypertension, diabetes, and previous myocardial infarction (MI). A higher prevalence of ankle-brachial index 640.90 was seen in patients with LVH (22 vs 17%, p = 0.0392). Patients with LVH were at significantly higher thromboembolic risk, with CHA2DS2-VASc 652 seen in 93% of LVH and in 73% of patients without LVH (p &lt;0.05). Women with LVH had a higher prevalence of concentric hypertrophy than men (46% vs 29%, p = 0.0003). Logistic regression analysis demonstrated that female gender (odds ratio [OR] 2.80, p &lt;0.0001), age (OR 1.03 per year, p &lt;0.001), hypertension (OR 2.30, p &lt;0.001), diabetes (OR 1.62, p = 0.004), and previous MI (OR 1.96, p = 0.001) were independently associated with LVH. In conclusion, patients with NVAF have a high prevalence of LVH, which is related to female gender, older age, hypertension, and previous MI. These patients are at high thromboembolic risk and deserve a holistic approach to cardiovascular prevention