Evaluation of soluble P-selectin as a predictive biomarker in acute symptomatic pulmonary embolism: Insights from a prospective observational study.

BACKGROUND: Soluble P-selectin (sP-selectin) has been proposed as a potential biomarker for venous thromboembolism (VTE) diagnosis with interesting results. However, its role in predicting early mortality in pulmonary embolism (PE) remains unexplored. METHODS: This observational, prospective, single-center study enrolled consecutive patients aged 18 or older with confirmed acute symptomatic PE and no prior anticoagulation. The study aims to assess the prognostic capacity of sP-selectin measured at the time of PE diagnosis for short-term mortality and major bleeding. RESULTS: A total of 196 patients, with a mean age of 69.1 years (SD 17), were included, of whom 52.6% were male. Within 30 days, 9.7% of patients (n = 19) died, and 5.1% (n = 10) suffered major bleeding. PE risk stratification revealed 4.6% (n = 9) with high-risk PE, 34.7% (n = 68) with intermediate-high-risk PE, 38.3% (n = 75) with intermediate-low-risk PE, and 22.5% (n = 44) with low-risk PE according to the European Society of Cardiology score. Mean plasma sP-selectin levels were comparable between survivors and non-survivors (489.7 ng/mL ±63 vs. 497.3 ng/mL ±51; p = .9). The ROC curve for 30-day all-cause mortality and major bleeding yielded an AUC of 0.49 (95% CI 0.36-0.63) and 0.46 (95% CI 0.24-0.68), respectively. Multivariate and survival analyses were precluded due to lack of significance. CONCLUSIONS: sP-selectin was not useful for predicting short-term mortality or major bleeding in patients with acute symptomatic pulmonary embolism. Further studies are required to clarify the role of sP-selectin in VTE, particularly in prognosticating PE outcomes.

The prognostic value of blood cellular indices in pulmonary embolism.

Prognostication in acute pulmonary embolism (PE) requires reliable markers. While cellular indices such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII) appear promising, their utility in PE prognostication needs further exploration. We utilized data from the RIETE registry and the Loyola University Medical Center (LUMC) to assess the prognostic value of NLR, PLR, and SII in acute PE, using logistic regression models. The primary outcome was 30-day all-cause mortality. We compared their prognostic value versus the simplified Pulmonary Embolism Severity Index (sPESI) alone. We included 10 085 patients from RIETE and 700 from the LUMC. Thirty-day mortality rates were 4.6% and 8.3%, respectively. On multivariable analysis, an elevated NLR (>7.0) was associated with increased mortality (adjusted odds ratio [aOR]: 3.46; 95% CI: 2.60-4.60), outperforming the PLR > 220 (aOR: 2.36; 95% CI: 1.77-3.13), and SII > 1600 (aOR: 2.52; 95% CI: 1.90-3.33). The c-statistic for NLR in patients with low-risk PE was 0.78 (95% CI: 0.69-0.86). Respective numbers were 0.66 (95% CI: 0.63-0.69) and 0.68 (95% CI: 0.59-0.76) for intermediate-risk and high-risk patients. These findings were mirrored in the LUMC cohort. Among 9810 normotensive patients in RIETE, those scoring 0 points in sPESI and with an NLR ≤ 7.0 (35% of the population) displayed superior sensitivity (97.1%; 95% CI: 95.5-98.7) and negative predictive value (99.7%; 95% CI: 99.5-99.8) than sPESI alone (87.1%; 95% CI: 83.9-90.3, and 98.7%; 95% CI: 98.4-99.1, respectively) for 30-day mortality. The NLR is a significant prognostic marker for 30-day mortality in PE patients, especially useful to identify patients with very low-risk PE.

Use of Oral Anticoagulant Drugs in Patients with Pulmonary Hypertension.

Pulmonary hypertension (PH), in particular pulmonary arterial hypertension and chronic thromboembolic PH, burdens patients with relevant morbidity and mortality. The use of oral anticoagulants (OACs) seems able to mitigate the risk of adverse outcomes and death in these patients. Despite scarce evidence, the use of OAC is recommended to treat PH patients, mainly based on observational data. So far, data are still unclear about the impact of direct oral anticoagulant (DOACs), whereas vitamin K antagonists are the main drugs recommended. More data are needed to fully clarify the role of OAC and DOACs in PH patients.

Arterial and venous involvement in Behçet's syndrome: a narrative review.

Behçet syndrome (BS) is a unique type of vasculitis that affects veins and arteries of all sizes, leading to recurrent vascular events, mostly venous thrombosis. The prevalence of venous thromboembolism in BS patients ranges between 15 and 40%. Thrombosis is usually an early manifestation leading to diagnosis of BS in up to 40% of patients. BS is per se a model of inflammation-induced thrombosis. The primary autoimmune response activates lymphocytes that in turn produce a cytokine cascade that activates neutrophils, which modify the secondary structure of fibrinogen making it less susceptible to plasmin-induced lysis. This leads to endothelial dysfunction, platelet activation and overexpression of tissue factor leading to inflammatory thrombi, usually attached to the wall. The pathogenesis of thrombosis is especially relevant to direct the specific treatment, that is based on immunosuppression rather than anticoagulation. Superficial vein thrombosis (SVT) and deep vein thrombosis (DVT) are the most common form of thrombosis in BS, but thrombosis in atypical sites (cava vein, suprahepatic veins, intracardiac thrombus) and arterial involvement can also occur. We assessed the latest update of the European League Against Rheumatism recommendations for the management of BS. Vascular Behçet treatment is usually based of immunosuppressants, and the role of anticoagulation remains controversial. The use of interventional and surgical procedures should be carefully evaluated, due to the risk of triggering a vascular pathergy phenomenon.

Long-term follow-up of patients with venous thromboembolism and COVID-19: Analysis of risk factors for death and major bleeding.

INTRODUCTION: COVID-19 predisposes patients to a higher risk of venous thromboembolism (VTE), although the extent of these implications is unclear and the risk of bleeding has been poorly evaluated. To date, no studies have reported long-term outcomes of patients with COVID-19 and VTE. METHOD: Prospective observational study to evaluate long-term (90 days or more) outcomes of patients diagnosed with VTE (PE, DVT of the extremities, or both) in the setting of COVID-19. The main outcome of the study was a compound of major bleeding and death. RESULTS: The study comprised 100 patients (mean age 65 ± 13.9 years). At the time of VTE diagnosis, 66% patients were hospitalized, 34.8% of them in the ICU. Mean follow-up was 97.9 ± 23.3 days. During the study period, 24% patients died and median time to death was 12 (IQR: 2.25-20.75) days, 11% patients had major bleeding and median time to event was 12 (IQR: 5-16) days. The cause of death was PE in 5% and bleeding in 2% of patients. There were no VTE recurrences. The main study outcome occurred in 29% patients. Risk of death or major bleeding was independently associated with ICU admission (HR 12.2; 95% CI 3.0-48.3), thrombocytopenia (HR 4.5; 95% CI 1.2-16.5), and cancer (HR 21.6; 95% CI 1.8-259). CONCLUSION: In patients with COVID-19 and VTE, mortality and major bleeding were high and almost a third of deaths were VTE-related. The majority of complications occurred in the first 30 days. ICU admission, thrombocytopenia, and cancer are risk factors for poor prognosis.

Inflammatory Biomarkers in the Short-Term Prognosis of Venous Thromboembolism: A Narrative Review.

The relationship between inflammation and venous thrombosis is not well understood. An inflammatory response may be both the cause and consequence of venous thromboembolism (VTE). In fact, several risk factors of VTE modulate thrombosis through inflammatory markers. Acute pulmonary embolism (PE) is burdened by a remarkable mortality rate, up to 34% in severely ill patients presenting with hemodynamic instability. Initial mortality risk stratification is based on hemodynamic instability. Patients with a situation of hemodynamic stability require immediate further risk assessment based on clinical, imaging, and circulating biomarkers, as well as the presence of comorbidities. Some inflammatory biomarkers have shown potential usefulness in the risk stratification of patients with VTE, especially acute PE. C-reactive protein on admission is associated with 30-day mortality and bleeding in VTE patients. P-selectin is associated with right ventricle dysfunction in PE patients and might be associated with VTE recurrences and the extension of thrombosis. Tissue factor microparticles are associated with VTE recurrence in cancer-associated thrombosis. Other inflammatory biomarkers present scarce evidence (inflammatory cytokines, erythrocyte sedimentation rate, fibrinogen, leukocyte count). In this manuscript, we will review the prognostic role of different inflammatory biomarkers available both for clinical practice and research in VTE patients.

Pulmonary Embolism: A Practical Guide for the Busy Clinician.

Acute pulmonary embolism (PE) is the third most common acute cardiovascular condition, and its prevalence increases over time. D-dimer has a very high negative predictive value, and if normal levels of D-dimer are detected, the diagnosis of PE is very unlikely. The final diagnosis should be confirmed by computed tomographic scan. However, echocardiography is the most available, bedside, low-cost, diagnostic procedure for patients with PE. Risk stratification is of utmost importance and is mainly based on hemodynamic status of the patient. Patients with PE and hemodynamic stability require further risk assessment, based on clinical symptoms, imaging, and circulating biomarkers.

Cervical and Oropharyngeal Lymphogranuloma Venereum: Case Report and Literature Review.

Lymphogranuloma venereum (LGV) is a sexually transmitted infection caused by invasive serovars of Chlamydia trachomatis. There have been only a few case reports of oropharyngeal C. trachomatis infection complicated with cervical LGV. We report a case of a HIV-positive male patient with cervical LGV that presented a poor evolution despite appropriate treatment.

Idiopathic versus Provoked Renal Infarction: Characteristics and Long-Term Follow-Up of a Cohort of Patients in a Tertiary Hospital.

BACKGROUND: There is limited evidence on the etiology and outcomes of renal infarction. A provoking factor is identified only in one- to two-thirds of patients. METHODS: This is a retrospective observational study. The clinical characteristics and outcomes of patients with acute renal infarction were studied; the sample was divided into two groups according to the presence of at least one provoking factor at the time of diagnosis (atrial fibrillation, flutter, major thrombophilia, or renal artery malformations). RESULTS: The study comprised 59 patients with a mean age of 63 (±16.7) years and a follow-up period of 3.1 (±2.8) years. An identifiable provoking factor was found for 59.3% of the renal infarctions at the time of diagnosis, and atrial fibrillation was the most frequent one (in 49.2% of all patients). Renal impairment was found in 49.2% of the patients at diagnosis and in 50.8% of the patients 6 months after the event (p = 0.525). When compared with the idiopathic group, the patients with provoked infarction were older (69.8 vs. 57.9 years, p = 0.014) and had a higher rate of recurrence of arterial thrombosis during follow-up (18.8 vs. 0%, p = 0.028), but there were no differences in the rest of the baseline characteristics or in mortality rates. Six patients (10.2%) in the idiopathic group were diagnosed with atrial fibrillation during follow-up. CONCLUSIONS: Atrial fibrillation, both at diagnosis and at follow-up, is the most common identifiable cause of renal infarction; however, a significant number of patients are idiopathic, and these are younger, but they have a similar burden of cardiovascular disease and a lower risk of arterial recurrence.

Hemolytic Anemia as a Provoking Factor for Recurrent Venous Thromboembolism: A Case Report.

Warm antibody autoimmune hemolytic anemia (WAIHA) is a rare disease that leads to the destruction of red blood cells in the reticuloendothelial system through the mediation of agglutinins (immunoglobulin G (IgG) type in most cases) that attach to the erythrocyte wall at 37 °C. The association of WAIHA and venous thromboembolism (VTE) seems to be higher than other hemolytic disorders classically associated with VTE and there is a current investigation aimed at clarifying this association and establishing some criteria to use anticoagulant treatment in patients with WAIHA. Despite this, WAIHA is a rare cause for the development of recurrent VTE under secondary prophylactic anticoagulant treatment, with only a few cases described in the literature. We present the case of a patient who developed a recurrence of deep vein thrombosis during a WAIHA episode despite treatment with acenocoumarol and a review of the literature.

Prognostic Significance of Heart Failure in Acute Pulmonary Embolism: A Comprehensive Assessment of 30-Day Outcomes.

INTRODUCTION: Patients with heart failure (HF) are known to have an increased risk of pulmonary embolism (PE), but there is limited evidence regarding the prognostic implications of HF in patients with acute PE and the relationship between PE prognosis and left ventricular ejection fraction (LVEF). The primary objective of this study was the development of a composite outcome (mortality, major bleeding, and recurrence) within the first 30 days. The secondary objective was to identify the role of LVEF in predicting the development of early complications in patients with both HF and reduced LVEF. MATERIAL AND METHODS: A prospective study was conducted at two tertiary hospitals between January 2012 and December 2022 to assess differences among patients diagnosed with acute PE based on the presence or absence of a history of HF. Cox regression models were employed to assess the impact of HF and reduced LVEF on the composite outcome at 30 days. RESULTS: Out of 1991 patients with acute symptomatic PE, 7.13% had a history of HF. Patients with HF were older and had more comorbidities. The HF group exhibited higher mortality (11.27% vs. 4.33%, p < 0.001) and a higher incidence of major bleeding (9.86% vs. 4.54%, p = 0.005). In the multivariate analysis, HF was an independent risk factor for the development of the composite outcome (HR 1.93; 95% CI 1.35-2.76). Reduced LVEF was independently associated with a higher risk of major bleeding (HR 3.44; 95% CI 1.34-8.81). CONCLUSION: In patients with acute pulmonary embolism, heart failure is independently associated with a higher risk of early complications. Additionally, heart failure with reduced LVEF is an independent risk factor for major bleeding.

Platypnea-Orthodeoxia Syndrome and COVID-19 Successfully Treated With Percutaneous Patent Foramen Ovale Closure: A Report of Two Cases and Literature Review.

Platypnea-orthodeoxia syndrome (POS) is a rare clinical condition characterized by positional dyspnea and/or hypoxia. We report two cases of patients with COVID-19 bronchopneumonia with a torpid evolution. Due to clinical suspicion of POS, a diagnostic workup was performed, including a bubble echocardiography, which revealed a patent foramen ovale (PFO) with early and massive passage of bubbles to the left cavities. Both patients underwent percutaneous PFO closure with a resolution of POS. Here, we present the second and third cases of POS associated with PFO successfully closed during the acute phase of COVID-19. This suggests that PFO closure could be a potential treatment option for this condition.

Soluble urokinase type plasminogen activator receptor (suPAR) and mortality in acute pulmonary embolism.

INTRODUCTION: The soluble urokinase-type plasminogen activator receptor (suPAR) potentially plays a role in immune-thrombosis, possibly by modulating plasmin activity or contributing to chemotaxis in a complex, poorly understood context. The role of suPAR levels in the short-term prognostic of patients with pulmonary embolism (PE) has not been evaluated. MATERIAL AND METHODS: This observational, prospective, single-center study enrolled consecutive patients aged 18 and above with confirmed acute symptomatic PE and no prior anticoagulant therapy. The primary objective was to assess the prognostic capacity of suPAR levels measured at the time of diagnosis in terms of mortality. RESULTS: Fifty-two patients, with a mean age of 73.8 years (±17), were included, with gender distribution evenly split at 50%. Seven (13.5%) patients died. The ROC curve for mortality yielded an AUC of 0.72 (95% CI 0.48-0.96), with an optimal suPAR cut-off of 5.5ng/mL. Bivariate analysis for suPAR>5.5ng/mL was associated with a crude odds ratio of 10 (95% CI 1.63-61.27; p=0.01) for 30-day mortality. Survival analysis showed a 30-day mortality hazard ratio of 8.33 (95% CI 1.69-40.99; p<0.01). CONCLUSION: suPAR emerges as a potential biomarker for short-term mortality prediction and holds the potential for enhanced stratification in patients with acute symptomatic PE.

The Potential Role of CA-125 as a Biomarker for Short-Term Mortality Risk in Patients with Acute Symptomatic Pulmonary Embolism.

Background: Antigen carbohydrate 125 (CA-125) is a complex glycoprotein extensively studied as a prognostic biomarker in heart failure, yet its potential role in the short-term prognosis of an acute pulmonary embolism (PE) remains unexplored. Methods: In this observational, prospective, single-center study, consecutive patients aged 18 and older with a confirmed acute symptomatic PE and no history of prior anticoagulant therapy were enrolled. Primary and secondary objectives aimed to assess the prognostic capacity of CA-125 at PE diagnosis for 30-day mortality and major bleeding, respectively. Results: A total of 164 patients were included (mean age 69.8 years, SD 17), with 56.1% being male. Within 30 days, 17 patients (10.4%) died and 9 patients (5.5%) suffered major bleeding. ROC curve analysis for 30-day mortality yielded an area under the curve of 0.69 (95% CI 0.53-0.85) with an optimal CA-125 cut-off point of 20 U/mL and a negative predictive value of 96%. Multivariate analysis revealed a significant association between CA-125 levels exceeding 20 U/mL and 30-day mortality (adjusted odds ratio 4.95; 95% CI 1.61-15.2) after adjusting for age, cancer, NT-proBNP > 600 ng/mL, and the simplified pulmonary embolism severity index score. Survival analysis for 30-day mortality exhibited a hazard ratio of 5.47 (95% CI 1.78-16.8). No association between CA-125 levels and 30-day major bleeding was found. Conclusions: CA-125 emerges as a promising surrogate biomarker for short-term mortality prediction in an acute symptomatic PE. Future investigations should explore the integration of CA-125 into PE mortality prediction scores to enhance the prognostic accuracy in this patient population.

A Rare Case of Stroke as a Complication After Percutaneous Mechanical Thrombectomy in a Patient with Intermediate-High Risk Pulmonary Embolism and Patent Foramen Ovale.

We present an extremely rare case of a patient with intermediate-high risk pulmonary embolism treated with percutaneous mechanical thrombectomy, complicated with stroke as a form of paradoxical embolism through a previously unknown patent foramen ovale. We reviewed the literature for indications, efficacy, and safety of this procedure, as well as for experience on this technique in patients with patent foramen ovale. LEARNING POINTS: Some authors propose percutaneous mechanical thrombectomy as an aggressive treatment of intermediate-high risk pulmonary embolism.Pending clinical trials, percutaneous mechanical thrombectomy seems to reduce right ventricle overload in these patients, with rare adverse effects.To our knowledge, this is the first reported case of stroke as a complication of the procedure. These patients should be screened for patent foramen ovale before the procedure.

[Clinical characteristics and presentation form in patients with venous thromboembolism and negative or weakly positive D-dimer]. / Características clínicas y forma de presentación en pacientes con enfermedad tromboembólica venosa y dímero-D negativo o débilmente positivo.

INTRODUCTION: D-dimer has a high negative predictive value for the diagnosis of venous thromboembolic disease (VTE). However, VTE has been reported in the presence of normal D-dimer values. METHODS: This is a prospective observational study in patients with VTE from Hospital Gregorio Marañón between 2001 and 2022, comparing the characteristics of clinical presentation based on D-dimer levels (<500 ng/mL vs. ≥500 ng/mL). RESULTS: A total of 2582 patients were found, 333 patients (12.9%) presented negative or weakly positive D-dimer levels. They were significantly younger (57.9 vs. 65.3 years), with a lower prevalence of comorbidities (ischemic heart disease, dementia, and chronic kidney disease), and a greater family history of VTE (8.4% vs. 5.2%) and thrombophilia (11.7% vs. 7.8%). They presented significantly less dyspnea (57.6% vs. 75.4%), syncope (3% vs. 13.5%), less thrombotic load, elevated NT-pro-BNP (22.0% vs. 48.2%), and right ventricle dilatation (8.1% vs. 30.0%). CONCLUSION: Patients with VTE and low D-dimer levels at diagnosis were younger, with milder clinical presentation and lower thrombotic load; but they presented a higher prevalence of thrombophilia and a family history of VTE.

COVID-19-associated venous thromboembolism: risk of recurrence and major bleeding.

Background: Complications under anticoagulant treatment in patients with COVID-19-associated venous thromboembolism (VTE) have not been consistently reported. Objectives: This study aimed to compare the 90-day rates of VTE recurrences and major bleeding in patients with COVID-19-associated VTE versus those with VTE without COVID-19. Methods: We used the RIETE registry to compare the 3-month outcomes in patients with COVID-19-associated VTE versus those with VTE without COVID-19. Results: The study included 1,747 patients with COVID-19-associated VTE and 8,711 with VTE without COVID-19. Patients with COVID-19-associated VTE were more likely to be hospitalized at baseline and to present with pulmonary embolism. During the first 90 days, 123 patients (1.17%) developed VTE recurrences, and 266 (2.54%) experienced major bleeding. Patients with COVID-19-associated VTE had a similar rate of VTE recurrences (0.9% vs 1.2%) but a higher rate of major bleeding (4.6% vs 2.1%; P < .001) than those without COVID-19. Multivariable analysis adjusted for competing risks showed that patients with COVID-19-associated VTE had an increased risk of major bleeding (subhazard ratio, 1.395; 95% confidence interval, 1.037-1.877). The 30-day mortality after major bleeding was 26.3% in patients with COVID-19-associated VTE and 17.7% in those without COVID-19. Conclusion: Patients with COVID-19-associated VTE had a 5-fold higher rate of major bleeding than VTE recurrences during the first 90 days of anticoagulation. In VTE patients without COVID-19, both rates were similar. These findings highlight the importance of carefully monitoring and optimizing anticoagulation in these patients.

Undertreatment or Overtreatment With Statins: Where Are We?

Statins, in addition to healthy lifestyle interventions, are the cornerstone of lipid-lowering therapy. Other low-density lipoprotein (LDL)-lowering drugs include ezetimibe, bile acid sequestrants, and PCSK9 inhibitors. As new evidence emerges from new clinical trials, therapeutic goals change, leading to renewed clinical guidelines. Nowadays, LDL goals are getting lower, leading to the "lower is better" paradigm in LDL-cholesterol (LDL-C) management. Several observational studies have shown that LDL-C control in real life is suboptimal in both primary and secondary preventions. It is critical to enhance the adherence to guideline recommendations through shared decision-making between clinicians and patients, with patient engagement in selecting interventions based on individual values, preferences, and associated conditions and comorbidities. This narrative review summarizes the evidence regarding the benefits of lipid-lowering drugs in reducing cardiovascular events, the pleiotropic effect of statins, real-world data on overtreatment and undertreatment of lipid-lowering therapies, and the changing LDL-C in targets in the clinical guidelines of dyslipidemias over the years.