Predicting intracranial bleeding during anticoagulation for venous thromboembolism within different time frames: Findings from the RIETE registry.

BACKGROUND: The risk of intracranial bleeding during anticoagulation for venous thromboembolism (VTE) is substantial and persists beyond the initial treatment phase. We aimed to refine risk-assessment through phase-specific prognostic scores. METHODS: We identified data from 77,786 VTE patients in the RIETE registry from March 2009 to October 2023 to develop two prognostic scores for intracranial bleeding. Multivariable Cox regression was used to analyze distinct variables for the early (≤90 days) and late (>90 days) phases, with comparative validation against existing scores (modified ACCP, RIETE, VTE-BLEED, and CHAP). RESULTS: Intracranial bleeding occurred in 411 patients (0.53 %), with 208 cases in the early phase and 203 in the late phase. The 30-day mortality was 45 % and 35 %, respectively. Shared significant predictors for both phases include baseline abnormal mental status, brain cancer, recent intracranial bleeding, and epilepsy. Unique to early-phase bleeding were body weight, non-brain cancer, hypertension, dementia, thrombocytopenia, renal insufficiency, and thrombolytic therapy. Advanced age, pulmonary embolism initially, prior stroke, depression, treatment with direct oral anticoagulants, and use of corticosteroids predicted late-phase bleeding. Both prognostic scores showed a c-statistic of 0.68, outperforming existing scores. CONCLUSIONS: The study introduces two temporal prognostic scores for intracranial bleeding during anticoagulation for VTE. By discerning specific risk factors pertinent to each treatment phase, these scores outperform traditional models, offering an advanced tool for clinical decision-making. They hold significant potential for optimizing anticoagulation management and reducing bleeding-related mortality.

Elderly Patients with Venous Thromboembolism: Insights from the RIETE Registry.

Venous thromboembolism (VTE) presents a notable healthcare burden, particularly among the elderly, who experience increased risks and more severe complications. This review aims to use the extensive data from the RIETE registry, a comprehensive database on consecutive patients with VTE. We examine the clinical features, therapeutic approaches, and patient outcomes of VTE in elderly patients, compared to younger patients, offering a comprehensive understanding of management challenges and emphasizing the need for strategies that accommodate the unique challenges of this population.

Rate of recurrence after discontinuing anticoagulation in patients with venous thromboembolism within 30 days after COVID-19 vaccine.

This study generated evidence to guide anticoagulation in patients with VTE after vaccination for COVID-19. We provided data on the low recurrence rate after cessation of anticoagulant therapy and the findings for this study offer timely insights into the management of a potentially vaccine-related adverse event.

The Structure-Antiproliferative Activity Relationship of Pyridine Derivatives.

Pyridine, a compound with a heterocyclic structure, is a key player in medicinal chemistry and drug design. It is widely used as a framework for the design of biologically active molecules and is the second most common heterocycle in FDA-approved drugs. Pyridine is known for its diverse biological activity, including antituberculosis, antitumor, anticoagulant, antiviral, antimalarial, antileishmania, anti-inflammatory, anti-Alzheimer's, antitrypanosomal, antimalarial, vasodilatory, antioxidant, antimicrobial, and antiproliferative effects. This review, spanning from 2022 to 2012, involved the meticulous identification of pyridine derivatives with antiproliferative activity, as indicated by their minimum inhibitory concentration values (IC50) against various cancerous cell lines. The aim was to determine the most favorable structural characteristics for their antiproliferative activity. Using computer programs, we constructed and calculated the molecular descriptors and analyzed the electrostatic potential maps of the selected pyridine derivatives. The study found that the presence and positions of the -OMe, -OH, -C=O, and NH2 groups in the pyridine derivatives enhanced their antiproliferative activity over the cancerous cellular lines studied. Conversely, pyridine derivatives with halogen atoms or bulky groups in their structures exhibited lower antiproliferative activity.

Decreased Thrombin Generation is Associated with Increased Thrombin Generation Biomarkers and Blood Cellular Indices in Pulmonary Embolism.

Pulmonary embolism (PE) is a heterogenous condition with variable clinical presentations. Thrombin generation potential (TGP) and biomarkers, and blood cellular indices can reflect the underlying pathophysiology and risk stratification of PE. This case-control study analyzed TGP in 209 PE patients from Loyola University, Pulmonary Embolism Response Team program compared to normal human plasma (NHP) controls. The present study evaluates TGP and biomarkers, and cellular indices in relation to PE severity, according to the European Society of Cardiology (ESC) guidelines. Statistical analysis including median with interquartile range (IQR), 2-tailed Wilcoxon Mann-Whitney test, Chi-square test, and Spearman Correlational analysis were performed. There were 209 patients with PE, with an almost equal distribution between sex, and a median age of 63 years. Significant downregulation in peak thrombin and endogenous thrombin potential (ETP), as well as upregulation in lag time, were observed in PE patients versus controls. Biomarker analysis revealed pronounced elevations, with D-dimer demonstrating the most significant increase. Blood cellular indices also rose in PE patients, correlating with disease severity. PE severity was associated with higher TGP and biomarker levels. Mortality rates differed significantly across risk categories and were highest in patients with elevated cellular indices. TGP and biomarkers are intricately linked to PE severity and can aid in risk stratification. Elevated cellular indices are associated with increased mortality, highlighting their potential as prognostic markers. These findings could enhance the precision of PE management strategies.

Comparative analysis of COVID-19-associated venous thromboembolism outcomes: evolution from 2020 to 2021-2022.

Patients with COVID-19 are at an increased risk for venous thromboembolism (VTE). With the advent of vaccinations and novel treatments from 2020 through 2022, the landscape of COVID-19 has evolved. Notably, the effects of such interventions on the outcomes of COVID-19-associated VTE have not been thoroughly examined. Data from the RIETE registry were analyzed to evaluate 90-day VTE-related outcomes (all-cause mortality, major bleeding, and VTE recurrences) in patients with COVID-19-associated VTE. We compared the periods before and after the widespread introduction of COVID-19 vaccines: March to December 2020 (pre-vaccine period) and March 2021 to December 2022 (post-vaccine period). Statistical analysis included mixed-effects parametric survival-time models. Among 1,620 patients with COVID-19-associated VTE, most (74.1%) were identified during 2020 period. The analysis revealed a more than two-fold increase in the risk of death within 90 days (adjusted hazard ratio [HR]: 2.27; 95% confidence interval, CI: 1.18-4.38) and major bleeding (adjusted HR: 2.91; 95%CI: 1.08-7.84) for patients from the 2020 period compared to those from the 2021-2022 period. Inpatient subgroup analysis confirmed the observed mortality differences. The frequency of recurrent VTE was low (1.1 vs. 0.7%, respectively), and did not show significant variation between the two periods. Our research provides a comparative perspective on the clinical outcomes of COVID-19-associated VTE before and after the introduction of vaccines. Our findings reveal a significant decrease in the incidence of 90-day mortality and major bleeding in patients with COVID-19-associated VTE in the 2021-2022 period.

Venous thromboembolism in women with hormone-dependent breast cancer. To continue or discontinue hormonal treatment? Insights from the RIETE registry.

INTRODUCTION: Hormone therapy (HT) for breast cancer is associated with an increased risk of venous thromboembolism (VTE). This study examines the effects of continuing versus discontinuing HT on VTE recurrence, major bleeding, and mortality, after an acute VTE event. METHODS: Using data in the RIETE-registry from March 2001 through September 2021, we calculated incidence rates and rate-ratios (RR) for VTE events in patients on- and off HT. Cox regression models assessed the impact of HT continuation. RESULTS: Among 479 women with breast cancer on HT who developed VTE (pulmonary embolism 279, isolated deep vein thrombosis 200), 350 (73 %) continued HT. These women were slightly older (70 ± 13 vs. 67 ± 16 years) than those discontinuing HT, with no significant differences in other baseline characteristics. Over a median follow-up of 294 days, 25 (5.2 %) developed VTE recurrences, 18 (3.7 %) had major bleeding, and 73 (15.2 %) died. Rates of VTE recurrence did not differ significantly between groups (RR: 1.28, 95 % CI 0.44-3.75), except in the first three months post-VTE, where a higher rate was observed in those continuing HT (6.02/100 patients-year vs. no events). On multivariable analysis, HT continuation showed no association with VTE recurrences after adjusting for other thromboembolic risk factors (adjusted hazard ratio [aHR] 1.49, 95 % CI 0.5-4.45). CONCLUSION: Continuing HT after a VTE event in women with breast cancer does not generally affect the long-term risk of VTE recurrences but is associated with a higher risk in the first three months. These findings highlight the need for careful monitoring during this period.

Risk of recurrence after discontinuing anticoagulation in patients with COVID-19- associated venous thromboembolism: a prospective multicentre cohort study.

Background: The clinical relevance of recurrent venous thromboembolism (VTE) after discontinuing anticoagulation in patients with COVID-19-associated VTE remains uncertain. We estimated the incidence rates and mortality of VTE recurrences developing after discontinuing anticoagulation in patients with COVID-19-associated VTE. Methods: A prospective, multicenter, non-interventional study was conducted between March 25, 2020, and July 26, 2023, including patients who had discontinued anticoagulation after at least 3 months of therapy. All patients from the registry were analyzed during the study period to verify inclusion criteria. Patients with superficial vein thrombosis, those who did not receive at least 3 months of anticoagulant therapy, and those who were followed for less than 15 days after discontinuing anticoagulation were excluded. Outcomes were: 1) Incidence rates of symptomatic VTE recurrences, and 2) fatal PE. The rate of VTE recurrences was defined as the number of patients with recurrent VTE divided by the patient-years at risk of recurrent VTE during the period when anticoagulation was discontinued. Findings: Among 1106 patients with COVID-19-associated VTE (age 62.3 ± 14.4 years; 62.9% male) followed-up for 12.5 months (p25-75, 6.3-20.1) after discontinuing anticoagulation, there were 38 VTE recurrences (3.5%, 95% confidence interval [CI]: 2.5-4.7%), with a rate of 3.1 per 100 patient-years (95% CI: 2.2-4.2). No patient died of recurrent PE (0%, 95% CI: 0-7.6%). Subgroup analyses showed that patients with diagnosis in 2021-2022 (vs. 2020) (Hazard ratio [HR] 2.86; 95% CI 1.45-5.68) or those with isolated deep vein thrombosis (vs. pulmonary embolism) (HR 2.31; 95% CI 1.19-4.49) had significantly higher rates of VTE recurrences. Interpretation: In patients with COVID-19-associated VTE who discontinued anticoagulation after at least 3 months of treatment, the incidence rate of recurrent VTE and the case-fatality rate was low. Therefore, it conceivable that long-term anticoagulation may not be required for many patients with COVID-19-associated VTE, although further research is needed to confirm these findings. Funding: Sanofi and Rovi, Sanofi Spain.

Clinical outcomes after discontinuing anticoagulant therapy in patients with first unprovoked venous thromboembolism.

BACKGROUND: The duration of anticoagulation for a first episode of unprovoked venous thromboembolism (VTE) should balance the likelihood of VTE recurrence against the risk of major bleeding. OBJECTIVES: Analyze rates and case-fatality rates (CFRs) of recurrent VTE and major bleeding after discontinuing anticoagulation in patients with a first unprovoked VTE after at least 3 months of anticoagulation. METHODS: We compared the rates and CFRs in patients of the Registro Informatizado Enfermedad Trombo Embólica (RIETE) and Contemporary management and outcomes in patients with venous thromboembolism registries. We used logistic regression models to identify predictors for recurrent pulmonary embolism (PE) and major bleeding. RESULTS: Of 8261 patients with unprovoked VTE in RIETE registry, 4012 (48.6%) had isolated deep vein thrombosis (DVT) and 4250 had PE. Follow-up (median, 318 days) showed 543 recurrent DVTs, 540 recurrent PEs, 71 major bleeding episodes, and 447 deaths. The Contemporary management and outcomes in patients with venous thromboembolism registry yielded similar results. Corresponding CFRs of recurrent DVT, PE, and major bleeding were 0.4%, 4.6%, and 24%, respectively. On multivariable analyses, initial PE presentation (hazard ratio [HR], 3.03; 95% CI, 2.49-3.69), dementia (HR, 1.47; 95% CI, 1.01-2.13), and anemia (HR, 0.72; 95% CI, 0.57-0.91) predicted recurrent PE, whereas older age (HR, 2.11; 95% CI, 1.15-3.87), inflammatory bowel disease (HR, 4.39; 95% CI, 1.00-19.3), and anemia (HR, 2.24; 95% CI, 1.35-3.73) predicted major bleeding. Prognostic scores were formulated, with C statistics of 0.63 for recurrent PE and 0.69 for major bleeding. CONCLUSION: Recurrent DVT and PE were frequent but had low CFRs (0.4% and 4.6%, respectively) after discontinuing anticoagulation. On the contrary, major bleeding was rare but had high CFR (24%). A few clinical factors may predict these 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.

Venous thromboembolism characteristics and outcomes among RIETE patients tested and untested for inherited thrombophilia.

ABSTRACT: Inherited thrombophilia (IT) workup is commonly pursued in patients with venous thromboembolism (VTE). Recent American Society of Hematology guidelines recommend a selective approach to IT testing, nevertheless, evidence on whether thrombophilia testing can actually improve patient-important outcomes through tailored management is limited. Data from the large, prospective Registro Informatizado de Enfermedad TromboEmbólica (RIETE) registry were analyzed to compare VTE risk factors, management, and outcomes between patients who were tested for IT and untested patients, during anticoagulant treatment and after its discontinuation. Among 103 818 patients enrolled in RIETE, 21 089 (20.3%) were tested for IT, 8422 (8.1%) tested positive, and 82 729 (79.7%) were not tested. IT testing was more frequent in patients with VTE provoked by minor risk factors and less common in those with major risk factors such as surgery or active cancer. Choices of anticoagulant treatment did not differ based on IT testing results. Untested patients exhibited inferior outcomes across all VTE categories, with higher rates of VTE recurrence, major bleeding, mortality, and notably, cancer-related mortality. After treatment discontinuation, IT-negative patients with surgically provoked VTE showed lower recurrence rates. For immobilization-related VTE as well as in estrogen-related VTE, no significant differences in recurrence rates were observed between IT-negative and IT-positive patients. However, IT-negative patients with pregnancy or postpartum-related VTE had significantly lower recurrence rates. Patients with unprovoked VTE, particularly those testing positive for IT, had high recurrence rates after treatment. These findings underscore the complex role of IT testing in managing VTE, supporting personalized treatment strategies that consider VTE risk factors and comorbidities. The trial was registered at www.clinicaltrials.gov as #NCT02832245.

Venous thromboembolism (VTE) developing after ankle sprain. Comparison with VTE after knee arthroplasty.

BACKGROUND: Venous thromboembolism (VTE) is a critical complication after non-major trauma or surgery. While the risk and severity of VTE following major orthopedic surgery is well-documented, there is significant knowledge gap regarding, non-major trauma such as ankle sprains. METHODS: We analyzed data from the RIETE registry to assess the clinical characteristics, VTE prophylaxis usage, and outcomes in patients with VTE following ankle sprain versus those post elective knee arthroplasty. We aimed to assess the risk and severity of VTE in a population traditionally considered at lower risk. Risk stratification was performed using the TRiP(cast) score. RESULTS: Among 1,250 patients with VTE, those with ankle sprain (n = 459) were much younger than those post knee arthroplasty (n = 791), less often female, had fewer comorbidities, and received VTE prophylaxis less often (27% vs. 93 %). During anticoagulation, 26 patients developed recurrent VTE, 31 had major bleeding, and 12 died (fatal PE 3, fatal bleeding 2). There were no differences between the two groups in the rates of VTE recurrences (rate ratio (RR): 1.65; 95%CI: 0.69-3.88) or death (RR: 1.12; 95%CI: 0.33-3.46), but patients with VTE after ankle sprain had a lower rate of major bleeding (RR: 0.39; 95%CI: 0.13-0.99). CONCLUSIONS: Ankle sprain patients are often undertreated for VTE prophylaxis and have similar severity of VTE than those undergoing elective knee surgery, indicating the need for a more customized approach to VTE management.

Fibrinolytic Agents in Thromboembolic Diseases: Historical Perspectives and Approved Indications.

Fibrinolytic agents catalyze the conversion of the inactive proenzyme plasminogen into the active protease plasmin, degrading fibrin within the thrombus and recanalizing occluded vessels. The history of these medications dates to the discovery of the first fibrinolytic compound, streptokinase, from bacterial cultures in 1933. Over time, researchers identified two other plasminogen activators in human samples, namely urokinase and tissue plasminogen activator (tPA). Subsequently, tPA was cloned using recombinant DNA methods to produce alteplase. Several additional derivatives of tPA, such as tenecteplase and reteplase, were developed to extend the plasma half-life of tPA. Over the past decades, fibrinolytic medications have been widely used to manage patients with venous and arterial thromboembolic events. Currently, alteplase is approved by the U.S. Food and Drug Administration (FDA) for use in patients with pulmonary embolism with hemodynamic compromise, ST-segment elevation myocardial infarction (STEMI), acute ischemic stroke, and central venous access device occlusion. Reteplase and tenecteplase have also received FDA approval for treating patients with STEMI. This review provides an overview of the historical background related to fibrinolytic agents and briefly summarizes their approved indications across various thromboembolic diseases.

Optimizing antithrombotic therapy in patients with coexisting cardiovascular and gastrointestinal disease.

Balancing the safety and efficacy of antithrombotic agents in patients with gastrointestinal disorders is challenging because of the potential for interference with the absorption of antithrombotic drugs and for an increased risk of bleeding. In this Review, we address considerations for enteral antithrombotic therapy in patients with cardiovascular disease and gastrointestinal comorbidities. For those with gastrointestinal bleeding (GIB), we summarize a general scheme for risk stratification and clinical evidence on risk reduction approaches, such as limiting the use of concomitant medications that increase the risk of GIB and the potential utility of gastrointestinal protection strategies (such as proton pump inhibitors or histamine type 2 receptor antagonists). Furthermore, we summarize the best available evidence and potential gaps in our knowledge on tailoring antithrombotic therapy in patients with active or recent GIB and in those at high risk of GIB but without active or recent GIB. Finally, we review the recommendations provided by major medical societies, highlighting the crucial role of teamwork and multidisciplinary discussions to customize the antithrombotic regimen in patients with coexisting cardiovascular and gastrointestinal diseases.

Outcomes of venous thromboembolism in patients with inherited thrombophilia treated with direct oral anticoagulants: insights from the RIETE registry.

While direct oral anticoagulants (DOACs) are frequently used to treat venous thromboembolism (VTE), the outcomes of patients with inherited thrombophilia (IT) receiving DOACs for VTE remain understudied. We used data from the international RIETE registry to compare the rates of VTE recurrences, major bleeding, and mortality during anticoagulant treatment in VTE patients with and without IT, grouped by the use of DOACs or standard anticoagulant therapy. Among 103,818 enrolled patients, 21,089 (20.3%) were tested for IT, of whom 8422 (39.9%) tested positive: Protein C deficiency 294, Protein S deficiency 726, Antithrombin deficiency 240, Factor V Leiden 2248, Prothrombin gene mutation 1434, combined IT 3480. Overall, 14,189 RIETE patients (6.2% with IT) received DOACs, and 89,629 standard anticoagulation (8.4% with IT), mostly with heparins followed by vitamin K antagonists. Proportions of patients receiving DOACs did not differ between IT-positive and IT-negative patients. Rates of VTE recurrence on anticoagulant treatment were highest in patients with AT deficiency (P < 0.01). Rates of on-treatment major bleeding and all-cause mortality were lowest among patients with Factor V Leiden (FVL) or PT G20210A mutations, compared with patients who tested negative. Patients with IT who received DOACs had lower rates of major bleeding than those receiving standard anticoagulation. Excluding FVL and Protein S deficiency, patients with IT had lower rates of VTE recurrence with DOACs than with standard anticoagulation. DOACs are equally safe and effective in VTE patients with IT, with lower bleeding rates than those on standard anticoagulation.

Statin use and mortality in patients with deep vein thrombosis. Data from the RIETE Registry.

BACKGROUND: The association between statin use and mortality in patients with deep vein thrombosis (DVT) has not been rigorously evaluated. METHODS: 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. RESULTS: 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. CONCLUSIONS: Statin users with isolated DVT were at significantly lower risk for death at 3 months than non-users.

Validation of Echocardiographic Measurements in Patients with Pulmonary Embolism in the RIETE Registry.

Background In acute pulmonary embolism (PE), echocardiographic identification of right ventricular (RV) dysfunction will inform prognostication and clinical decision-making. Registro Informatizado Enfermedad TromboEmbolica (RIETE) is the world's largest registry of patients with objectively confirmed PE. The reliability of site-reported RV echocardiographic measurements is unknown. We aimed to validate site-reported key RV echocardiographic measurements in the RIETE registry. Methods Fifty-one randomly chosen patients in RIETE who had transthoracic echocardiogram (TTE) performed for acute PE were included. TTEs were de-identified and analyzed by a core laboratory of two independent observers blinded to site-reported data. To investigate reliability, intraclass correlation coefficients (ICCs) and Bland-Altman plots between the two observers, and between an average of the two observers and the RIETE site-reported data were obtained. Results Core laboratory interobserver variations were very limited with correlation coefficients >0.8 for all TTE parameters. Agreement was substantial between core laboratory observers and site-reported data for key parameters including tricuspid annular plane systolic excursion (ICC 0.728; 95% confidence interval [CI], 0.594-0.862) and pulmonary arterial systolic pressure (ICC 0.726; 95% CI, 0.601-0.852). Agreement on right-to-left ventricular diameter ratio (ICC 0.739; 95% CI, 0.443-1.000) was validated, although missing data limited the precision of the estimates. Bland-Altman plots showed differences close to zero. Conclusion We showed substantial reliability of key RV site-reported measurements in the RIETE registry. Ascertaining the validity of such data adds confidence and reliability for subsequent investigations.

When Direct Oral Anticoagulants Should Not Be Standard Treatment: JACC State-of-the-Art Review.

For most patients, direct oral anticoagulants (DOACs) are preferred over vitamin K antagonists for stroke prevention in atrial fibrillation and for venous thromboembolism treatment. However, randomized controlled trials suggest that DOACs may not be as efficacious or as safe as the current standard of care in conditions such as mechanical heart valves, thrombotic antiphospholipid syndrome, and atrial fibrillation associated with rheumatic heart disease. DOACs do not provide a net benefit in conditions such as embolic stroke of undetermined source. Their efficacy is uncertain for conditions such as left ventricular thrombus, catheter-associated deep vein thrombosis, cerebral venous sinus thrombosis, and for patients with atrial fibrillation or venous thrombosis who have end-stage renal disease. This paper provides an evidence-based review of randomized controlled trials on DOACs, detailing when they have demonstrated efficacy and safety, when DOACs should not be the standard of care, where their safety and efficacy are uncertain, and areas requiring further research.

Developmental or Procedural Vena Cava Interruption and Venous Thromboembolism: A Review.

The inferior vena cava (IVC) and superior vena cava are the main conduits of the systemic venous circulation into the right atrium. Developmental or procedural interruptions of vena cava might predispose to stasis and deep vein thrombosis (DVT) distal to the anomaly and may impact the subsequent rate of pulmonary embolism (PE). This study aimed to review the various etiologies of developmental or procedural vena cava interruption and their impact on venous thromboembolism. A systematic search was performed in PubMed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines per each clinical question. For management questions with no high-quality evidence and no mutual agreements between authors, Delphi methods were used. IVC agenesis is the most common form of congenital vena cava interruption, is associated with an increased risk of DVT, and should be suspected in young patients with unexpected extensive bilateral DVT. Surgical techniques for vena cava interruption (ligation, clipping, and plication) to prevent PE have been largely abandoned due to short-term procedural risks and long-term complications, although survivors of prior procedures are occasionally encountered. Vena cava filters are now the most commonly used method of procedural interruption, frequently placed in the infrarenal IVC. The most agreed-upon indication for vena cava filters is for patients with acute venous thromboembolism and coexisting contraindications to anticoagulation. Familiarity with different forms of vena cava interruption and their local and systemic adverse effects is important to minimize complications and thrombotic events.