Characteristics of Young Women Presenting With Acute Myocardial Infarction: The Prospective, Multicenter, Observational Young Women Presenting Acute Myocardial Infarction in France Study.

BACKGROUND: The percentage of women <50 years of age hospitalized with myocardial infarction is increasing. We describe the clinical, morphological, and biological characteristics, as well as the clinical outcomes of this population. METHODS AND RESULTS: This prospective, observational study included consecutive women <50 years of age admitted for myocardial infarction at 30 centers in France (May 2017-June 2019). The primary outcome was the composite of net adverse clinical events: all-cause death, cardiovascular death, recurrent myocardial infarction, stent thrombosis, any stroke, or major bleeding occurring during hospitalization with a 12-month follow up. Three hundred fourteen women were included. The mean age was 43.0 (±5.7) years, 60.8% presented with ST-segment-elevation myocardial infarction, 75.5% were current smokers, 31.2% had a history of complicated pregnancy, and 55.1% reported recent emotional stress. Most (91.6%) women presented with typical chest pain. Of patients on an estrogen-containing contraceptive, 86.0% had at least 1 contraindication. Of patients with ST-segment-elevation myocardial infarction, 17.8% had myocardial infarction with nonobstructive coronary arteries and 14.6% had spontaneous coronary artery dissection, whereas 29.3% presented with multivessel vessel disease. During hospitalization, 11 net adverse clinical events occurred in 9 (2.8%) women, but no deaths or stent thromboses occurred. By 12 months, 14 net adverse clinical events occurred in 10 (3.2%) women; 2 (0.6%) died (from progressive cancer) and 25 (7.9%) had an ischemia-driven repeat percutaneous coronary intervention. CONCLUSIONS: Most young women with myocardial infarction reported typical chest pain and had modifiable cardiovascular risk factors. History of adverse pregnancy outcomes and prescription of combined oral contraceptive despite a contraindication were prevalent, emphasizing the need for comprehensive cardiological and gynecological evaluation and follow-up. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03073447.

Duration of anticoagulation of venous thromboembolism.

Venous thromboembolism (VTE) is a common, serious condition that requires anticoagulation for at least three months to prevent recurrence and long-term complications. After this initial period, the decision to continue or stop anticoagulation depends on the balance between the risk of recurrent VTE and the risk of bleeding. Established guidelines suggest short-term anticoagulation for VTE caused by transient factors and indefinite anticoagulation for recurrent or cancer-associated VTE. However, for a first unprovoked VTE, decision-making remains challenging. Current predictive scores for recurrence and bleeding are not sufficiently reliable, and the safety and efficacy of reduced-dose anticoagulation remain unclear. In the future, precision and patient-centred medicine may improve treatment decisions in this area.

Impact of thrombophilia on venous thromboembolism management.

Hypercoagulable states, also called thrombophilia, can either be congenital or acquired. Congenital thrombophilia, associated mainly with venous thrombosis, is either secondary to coagulation-inhibitor deficiencies, i.e., antithrombin, protein C and Protein S, or gain of function mutations, i.e., factor V Leiden and prothrombin G20210A mutations. Despite the relative frequency of these two mutations, they have not been associated with venous thrombosis recurrence. Most prevalent thrombophilia have a limited impact and usually does not change indications for duration of antithrombotic treatment or prophylaxis compared to decisions based on clinical factors. However, rare inherited thrombophilia such as antithrombin deficiency could justify a long-term anticoagulation. The main acquired thrombophilia, the Antiphospholipid syndrome (APS), is associated with both arterial and venous thrombosis. Its impact on patient management is significant: choice of the anticoagulant (DOAC vs. warfarin), duration of anticoagulation, screening of any organ involvement and systemic autoimmune disease, introduction of immunosuppressive therapy.

Predictors of pulmonary embolism in chronic obstructive pulmonary diseases patients admitted for worsening respiratory symptoms: An individual participant data meta-analyses.

BACKGROUND: Pulmonary embolism (PE) and acute exacerbation of chronic obstructive pulmonary disease (COPD) have similar clinical symptoms, making PE diagnosis challenging. Previous studies have shown that the prevalence of PE among COPD patients admitted with worsening respiratory symptoms was not negligible, but that systematic search for PE did not provide a clinical benefit. Predictive factors for PE remain unknown. OBJECTIVE: to identify predictive factors for PE among COPD patients with worsening respiratory symptoms. METHODS: We conducted an individual participant data meta-analysis which included the patients from the prospective PEP cohort and those randomized to the intervention arm in the SLICE trial which included a systematic search for PE in COPD patients admitted for worsening respiratory symptoms. Univariable and multivariable analysis were used to assess factors associated with the diagnosis of PE during the initial management. RESULTS: Among 1110 COPD patients, PE was diagnosed in 61 (5.49 %; 95 %CI 4.15 %-6.84 %). In univariable analysis, BNP (Brain natriuretic peptide) (odds ratio [OR] 1.02 per 100 ng/L increase, 95 %CI 1.01-1.04), prothrombin time (OR 0.78, 95 %CI 0.65-0.94), fibrinogen (OR 0.80, 95 %CI 0.64-0.98), atrial fibrillation (OR 4.74, 95 %CI 1.84-10.80), respiratory rate ≥30 min (OR 2.34, 95 %CI 1.13-4.6) and recent medical immobilization (OR 1.79, 95 %CI 0.99-3.13]) were associated with the risk of PE diagnosed during the initial management. In multivariable analysis, respiratory rate ≥30 (OR 2.77, 95 %CI 1.08-6.71) was a predictive factor for PE, as well as BNP (OR 1.02, 95 %CI 1.00-1.05) with an area under the curve =0.64, negative predictive value =0.15 (95 %CI 0.09-0.23), sensitivity =0.78 (95 %CI 0.74-0.82) and specificity =0.46 (95 %CI 0.29-0.63). CONCLUSION: Among patients with COPD admitted for worsening respiratory symptoms, respiratory rate and BNP levels are predictor of PE, but with limited discriminatory power.

Predelivery Haemostatic Biomarkers in Women with Non-Severe Postpartum Haemorrhage.

Background: Postpartum haemorrhage (PPH) is a frequent complication of childbirth that is difficult to predict. Predelivery coagulation biomarkers may help to guide preventive strategies. Our objective was to evaluate the association of predelivery haemostatic biomarkers with non-severe PPH. Methods: A nested case-control study was conducted within the « Study of Biological Determinants of Bleeding Postpartum ¼ in order to compare different haemostatic biomarkers in plasma from pregnant women with non-severe PPH (cases) and controls without PPH matched for age, body mass index, term, and mode of delivery. Blood was collected at entry in the delivery room. Global haemostatic assays (thrombin generation assay (TGA) and plasmin generation assay (PGA)) were then performed on freshly thawed aliquots of platelet-poor plasma. Results: A total of 370 pregnant women (185 cases and 185 controls) were included. Median [interquartile range] predelivery platelet count was lower in PPH cases than in controls (217 [181-259] versus 242 [196-280] G/L). TGA and PGA parameters were similar between cases and controls. In a subset analysis of vaginal deliveries (n = 144), median predelivery TGA thrombin peak was lower, and median predelivery PGA lag phase was longer in cases compared to controls. In multivariable analysis, only predelivery platelet count was independently associated with non-severe PPH. Conclusions: Predelivery platelet count is associated with non-severe PPH. Differences in other haemostatic parameters are tenuous, questioning their usefulness in predicting non-severe PPH.

Safety of treating acute pulmonary embolism at home: an individual patient data meta-analysis.

BACKGROUND AND AIMS: Home treatment is considered safe in acute pulmonary embolism (PE) patients selected by a validated triage tool (e.g. simplified PE severity index score or Hestia rule), but there is uncertainty regarding the applicability in underrepresented subgroups. The aim was to evaluate the safety of home treatment by performing an individual patient-level data meta-analysis. METHODS: Ten prospective cohort studies or randomized controlled trials were identified in a systematic search, totalling 2694 PE patients treated at home (discharged within 24 h) and identified by a predefined triage tool. The 14- and 30-day incidences of all-cause mortality and adverse events (combined endpoint of recurrent venous thromboembolism, major bleeding, and/or all-cause mortality) were evaluated. The relative risk (RR) for 14- and 30-day mortalities and adverse events is calculated in subgroups using a random effects model. RESULTS: The 14- and 30-day mortalities were 0.11% [95% confidence interval (CI) 0.0-0.24, I2 = 0) and 0.30% (95% CI 0.09-0.51, I2 = 0). The 14- and 30-day incidences of adverse events were 0.56% (95% CI 0.28-0.84, I2 = 0) and 1.2% (95% CI 0.79-1.6, I2 = 0). Cancer was associated with increased 30-day mortality [RR 4.9; 95% prediction interval (PI) 2.7-9.1; I2 = 0]. Pre-existing cardiopulmonary disease, abnormal troponin, and abnormal (N-terminal pro-)B-type natriuretic peptide [(NT-pro)BNP] at presentation were associated with an increased incidence of 14-day adverse events [RR 3.5 (95% PI 1.5-7.9, I2 = 0), 2.5 (95% PI 1.3-4.9, I2 = 0), and 3.9 (95% PI 1.6-9.8, I2 = 0), respectively], but not mortality. At 30 days, cancer, abnormal troponin, and abnormal (NT-pro)BNP were associated with an increased incidence of adverse events [RR 2.7 (95% PI 1.4-5.2, I2 = 0), 2.9 (95% PI 1.5-5.7, I2 = 0), and 3.3 (95% PI 1.6-7.1, I2 = 0), respectively]. CONCLUSIONS: The incidence of adverse events in home-treated PE patients, selected by a validated triage tool, was very low. Patients with cancer had a three- to five-fold higher incidence of adverse events and death. Patients with increased troponin or (NT-pro)BNP had a three-fold higher risk of adverse events, driven by recurrent venous thromboembolism and bleeding.

Extracellular RNA Induces Neutrophil Recruitment Via Toll-Like Receptor 3 During Venous Thrombosis After Vascular Injury.

BACKGROUND: Venous thromboembolism is associated with endothelial cell activation that contributes to the inflammation-dependent activation of the coagulation system. Cellular damage is associated with the release of different species of extracellular RNA (eRNA) involved in inflammation and coagulation. TLR3 (toll-like receptor 3), which recognizes (viral) single-stranded or double-stranded RNAs and self-RNA fragments, might be the receptor of these species of eRNA during venous thromboembolism. Here, we investigate how the TLR3/eRNA axis contributes to venous thromboembolism. METHODS AND RESULTS: Thrombus formation and size in wild-type and TLR3 deficient (-/-) mice were monitored by ultrasonography after venous thrombosis induction using the ferric chloride and stasis models. Mice were treated with RNase I, with polyinosinic-polycytidylic acid, a TLR3 agonist, or with RNA extracted from murine endothelial cells. Gene expression and signaling pathway activation were analyzed in HEK293T cells overexpressing TLR3 in response to eRNA or in human umbilical vein endothelial cells transfected with a small interference RNA against TLR3. Plasma clot formation on treated human umbilical vein endothelial cells was analyzed. Thrombosis exacerbated eRNA release in vivo and increased eRNA content within the thrombus. RNase I treatment reduced thrombus size compared with vehicle-treated mice (P<0.05). Polyinosinic-polycytidylic acid and eRNA treatments increased thrombus size in wild-type mice (P<0.01 and P<0.05), but not in TLR3-/- mice, by reinforcing neutrophil recruitment (P<0.05). Mechanistically, TLR3 activation in endothelial cells promotes CXCL5 (C-X-C motif chemokine 5) secretion (P<0.001) and NFκB (nuclear factor kappa-light-chain-enhancer of activated B cells) activation (P<0.05). Finally, eRNA triggered plasma clot formation in vitro (P<0.01). CONCLUSIONS: We show that eRNA and TLR3 activation enhance venous thromboembolism through neutrophil recruitment possibly through secretion of CXCL5, a potent neutrophil chemoattractant.

Full-dose rivaroxaban in patients with a history of bariatric surgery: bridging the knowledge gap through a phase 1 study.

BACKGROUND: Bariatric surgery (BS) induces significant changes in gastrointestinal anatomy, potentially influencing the pharmacokinetics of orally administered drugs such as rivaroxaban. OBJECTIVES: This phase 1 study aimed to assess the pharmacokinetics and safety of full-dose rivaroxaban in post-BS patients. METHODS: The ABSORB (Rivaroxaban Pharmacokinetics and Pharmacodynamics After Bariatric Surgery and in Morbid Obesity) study was a single-center, nonrandomized, multiple-dose, parallel-design bioequivalence trial. Adult patients with stable weight after Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) were compared with subjects with class III obesity and healthy controls. Participants received 20 mg of rivaroxaban daily for 8 days. RESULTS: Post-BS patients exhibited altered rivaroxaban pharmacokinetics, suggesting reduced absorption. Mean area under the concentration-time curve from time 0 to 24 hours after the first dose (RYGB, 1806.8 ng.h/mL; SG, 1648.9 ng.h/mL) was lower compared with that in controls (1893.5 ng.h/mL). At steady state, the area under the concentration-time curve values remained lower in BS groups (RYGB, 2129.9 ng.h/mL; SG, 1946.4 ng.h/mL) than in controls (2224.8 ng.h/mL). The maximum concentration after the first dose was lower in post-RYGB subjects (214.9 ng/mL) than in controls (264.1 ng/mL). This difference was less pronounced at steady state (RYGB, 256.9 ng/mL vs controls, 288.8 ng/mL). Neither BS group met bioequivalence criteria compared with controls, whereas the group with class III obesity met bioequivalence criteria compared with controls at steady state. CONCLUSION: Rivaroxaban displayed minor pharmacokinetic variations in post-BS patients. Given reported interindividual variability in the general population, these variations are unlikely to be of clinical significance. Our findings support rivaroxaban use in BS patients, emphasizing the need for further research in this area.

Chronic obstructive pulmonary disease exacerbation purulence status and its association with pulmonary embolism: protocol for a systematic review with meta-analysis.

INTRODUCTION: Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) increases the risk of pulmonary embolism (PE). AECOPD and PE have similar symptoms which results in a high proportion of patients with AECOPD undergoing imaging to rule out PE. Finding predictors and explanatory factors of PE in AECOPD, such as purulence status, could help reduce the need for imaging. This systematic review with meta-analysis aims to evaluate if there is an association between purulence status in AECOPD and PE diagnosis. METHODS AND ANALYSIS: MEDLINE, EMBASE and CENTRAL will be searched from database inception to April 2024. Randomised trials, cohort studies and cross-sectional studies on the prevalence of PE in patients with AECOPD will be included if the prevalence of PE based on the AECOPD purulence status is available. There will be no restriction on language. The primary outcome will be PE at the initial assessment and secondary outcomes will be all venous thromboembolism (deep venous thrombosis (DVT) and PE) and DVT, respectively, diagnosed at the initial assessment. Relative risks with their 95% CI will be calculated by using a Mantel-Haenszel random-effect model to compare the association between the risk of PE and the AECOPD purulence status (purulent vs non-purulent/unknown). Subgroup analyses will be performed based on the type of study, systematic search of PE versus no systematic search of PE and localisation of PE. Risk of bias will be evaluated by the ROBINS-E tool, publication bias will be evaluated with the funnel plot. The manuscript will be drafted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement. ETHICS AND DISSEMINATION: This study does not require ethics approval. This work will be submitted for presentation at an international conference and for publication in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42023459429.