High Risk Of Thromboembolic Events Research Articles

Atrial high-rate episodes detected by cardiac implantable electronic devices: arrhythmic burden and progression towards de-novo clinical atrial fibrillation

Abstract Background Atrial high rate episodes (AHRE) detected by cardiac implantable electronic devices (CIEDs) are associated with a higher risk of thromboembolic events, but whether oral anticoagulants (OACs) improve patient outcomes is still debated. On the other hand, OACs benefits in patients with clinical atrial fibrillation (AF) are well established. Therefore, the potential progression of AHRE towards clinical AF should be promptly recognized. Purpose To evaluate the incidence of de-novo clinical AF and its potential predictors. Methods Consecutive CIED patients presenting AHRE (with confirmation of an arrhythmia lasting 5 min–23 h 59 min, atrial rate 175/min, with no AF at 12-lead ECG and no prior clinical AF) were retrospectively enrolled. Potential predictors of incident clinical AF were investigated by building six different multivariable Cox’s regression analyses, and the duration of the single longest AHRE episode during follow-up was used as a time-dependent covariate. Results 126 patients (median age 79.7 (73.8-84.6), 34.1% female) had available follow-up data. Detailed patients' characteristics are provided in Figure 1. Over a median follow-up of 1128 (580-1646) days, 41/126 (32.5%) patients developed incident clinical AF. A single longest AHRE episode lasting ≥ 6 hours (h) was found associated with a higher risk of incident clinical AF after adjusting for HATCH score, female sex, and coronary artery disease (CAD) (Hazard ratio (HR) 2.82; 95%CI 1.32-6.04) and also in the model adjusting for CHA2DS2-VASc score and CKD (HR 3.13; 95%CI 11.57-6.25). Similar results were found for a single longest AHRE episode lasting ≥ 12 hours (HR 4.91; 95%CI 2.31-10.42 and HR 4.90; 95%CI 2.50-9.60, respectively), and lasting ≥ 24h (HR 4.40; 95%CI 1.82-10.60 and HR 4.56; 95%CI 2.05-10.14, respectively) (Figure 2). On the other hand, HATCH score and CHA2DS2-VASc score were independently associated with a higher risk of incident clinical AF only in multivariable models adjusting for episodes of AHRE lasting ≥6 h (HR 1.42; 95%CI 1.02-1.97 and HR 1.37; 95%CI 1.03-1.83, respectively) but this association was not confirmed after adjusting for AHRE of longer duration. Conclusions In patients with AHRE, the incidence of de-novo clinical AF is high in a three-year follow-up. Baseline patients’ characteristics (HATCH and CHA2DS2-VASc scores) and AHRE duration during follow-up may help to intensify monitoring and decision-making, being independently associated with incident clinical AF at follow-up.Baseline characteristicsMultivariate Cox's regression analysis

Neoplastic pathologic hip fractures are associated with a higher risk of post-operative bleeding and thromboembolic events

IntroductionSurgical treatment of hip fractures leads to significant post-operative complications. Although pathologic fractures (PF) are associated with worse outcomes, most studies do not differentiate between etiology (neoplastic and non-neoplastic PF). We seek to compare 30-day complication rates between 1) native hip fractures and neoplastic PF, and 2) neoplastic and non-neoplastic PF. Materials and methodsA total of 127,819 patients with hip fractures and 5104 with PF diagnosed from 2005 to 2021 were retrieved from the NSQIP database. We included 1843 patients with neoplastic PF and 3261 with non-neoplastic PF. Demographics, pre-operative labs and co-morbidities, and post-operative outcomes were analyzed. Propensity-score matching was conducted to control for confounders. ResultsPatients with a neoplastic PF had a significantly higher rate of deep venous thrombosis (DVT) (4 % vs 1.2 %, p = 0.001) and pulmonary embolism (PE) (2.4 % vs 0.7 %, p < 0.001), than native hip fractures. Rates of post-operative bleeding were significantly higher in the neoplastic PF group (29.3 % vs 23.9 %, p < 0.001) than non-neoplastic PF. No differences in soft tissue complications were found. When comparing neoplastic and non-neoplastic PF, the former had a higher rate of PE (2.5 % vs 1.0 %, p = 0.015) and post-operative bleeding (27.6 % vs 22.0 %, p = 0.009). Unplanned readmission rates and 30-day mortality rate were also higher in the neoplastic PF group. ConclusionNeoplastic PF of the hip are associated with higher risk of thromboembolic event rates and post-operative bleeding than both native hip fractures and non-neoplastic PF. No differences in rates of soft tissue complications were found between groups.

Effect of drug interactions with non-vitamin-K oral anticoagulants on thromboembolic events in patients with nonvalvular atrial fibrillation

Introduction: Few real-world studies have investigated drug-drug interactions (DDIs) involving non-vitamin-K antagonist oral anticoagulants (NOACs) in patients with nonvalvular atrial fibrillation (NVAF). The interactions encompass drugs inducing or inhibiting cytochrome P450 3A4 and permeability glycoprotein. These agents potentially modulate the breakdown and elimination of NOACs. This study investigated the impact of DDIs on thromboembolism in this clinical scenario. Method: Patients who had NVAF and were treated with NOACs were selected as the study cohort from the National Health Insurance Research Database of Taiwan. Cases were defined as patients hospitalised for a thromboembolic event and who underwent a relevant imaging study within 7 days before hospitalisa-tion or during hospitalisation. Each case was matched with up to 4 controls by using the incidence density sampling method. The concurrent use of a cytochrome P450 3A4/permeability glycoprotein inducer or inhibitor or both with NOACs was identified. The effects of these interactions on the risk of thromboembolic events were examined with univariate and multivariate conditional logistic regressions. Results: The study cohort comprised 60,726 eligible patients. Among them, 1288 patients with a thromboembolic event and 5144 matched control patients were selected for analysis. The concurrent use of a cytochrome P450 3A4/permeability glycoprotein inducer resulted in a higher risk of thromboembolic events (adjusted odds ratio [AOR] 1.23, 95% confidence interval [CI] 1.004–1.51). Conclusion: For patients with NVAF receiving NOACs, the concurrent use of cytochrome P450 3A4/ permeability glycoprotein inducers increases the risk of thromboembolic events.

RISK OF THROMBOEMBOLISM IN CHRONIC KIDNEY DISEASE PATIENTS WITH NON VALVULAR ATRIAL FIBRILLATION : A SYSTEMATIC REVIEW

Background: Individuals with CKD are at higher risk for thromboembolic events than those without CKD whilst also at a higher bleeding risk. NVAF often coexist with CKD and heightens the risk of one another. This study aimed to investigate the risk of thromboembolism in CKD patients with NVAF. Methods: This systematic review used Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) 2020 as standards. Inclusion criteria for literature eligibility are full-text literature, written in english, and published between 2014 and 2024. Exclusion criteria used for this study were editorials, review articles and identical journal that has been published, and submissions without DOI. Literatures were collected from online reference sources like Pubmed and SagePub. Result: In the PubMed database, the results of our search brought up 45 articles, whereas the results of our search on SagePub brought up 382 articles. The results of the search conducted for the last year of 2014 yielded a total 10 articles for PubMed and 12 articles for SagePub. In the end, we compiled a total of 5 papers, 3 of which came from PubMed and 2 of which came from SagePub. We included five research that met the criteria. Conclusion: The existence of both NVAF and CKD increase the risk of thromboembolic events. There are various modalities to analyze the risk of thromboembolism by assessing risk scores, kidney function, and utilizing transesophageal echocardiography (TEE). In order to prevent ischaemic stroke in NVAF patients, anticoagulants can be administered by in consideration to the kidney function.

A pilot study to evaluate the quality of care in oral anticoagulant and antiplatelet use in patients with permanent atrial fibrillation in Irish general practice

Abstract Aim: The aim of this pilot study is to determine the pattern of oral anticoagulant and antiplatelet use in patients with permanent atrial fibrillation (AF) in Irish general practice. Background: Worldwide, AF is the most common sustained cardiac arrhythmia in adults and poses a significant burden to patients, physicians and healthcare systems. There is a five-fold increased risk of stroke with AF, and AF-related strokes are associated with higher levels of both morbidity and mortality compared to other stroke subtypes. Thankfully, appropriate use of oral anticoagulation (OAC) for AF can reduce the risk of stroke by up to 64%. However, we know that patients are commonly undertreated with OAC, prescribed inappropriate doses of OAC and have prolonged use of an antiplatelet agent in addition to OAC without indication. Methods: A descriptive, cross-sectional observational study was undertaken. Proportionate sampling was used across 11 practices from the Ireland East practice-based research network. The general practitioners completed a report form on each patient provided by the research team by undertaking a retrospective chart review. Findings: Eleven practices participated with a total number of 1855 patients with AF. We received data on 153 patients. The main findings from this pilot project are that: 1. 11% of patients were undertreated with OAC 2. 20 % of patients were on an incorrect non-vitamin K antagonist oral anticoagulant dose 3. 28 patients (18%) were inappropriately prescribed combination antithrombotic therapy Undertreatment and underdosing of OAC expose patients to higher risk of thromboembolic events, bleeding and all-cause mortality. Prolonged combination antithrombotic therapy is associated with serious increased risk of bleeding with no additional stroke protection. This pilot project highlights several gaps between guidelines and clinical practice. By identifying these areas, we hope to develop a targeted quality improvement intervention using the electronic health records in general practice to improve the care that those with AF receive.

Real-World Analysis of Thromboembolic Event Rates in Patients in the United States with Polycythemia Vera

Background:Polycythemia vera (PV) is a myeloproliferative neoplasm associated with an increased risk of thromboembolic events (TEs). PV patients are characterized based on their risk for TEs as low-risk (age &amp;lt;60 without prior history of TE) or high-risk (age ≥60 and/or prior history of TE). Observational studies have shown higher rates of TEs in PV patients compared to matched controls (14.3 vs 4.9/1000 patient years, or PY), with rates as high as 40% in patients with PV (Goyal et al., Blood. 2014;124:4840; Griesshammer et al., Ann Hematol. 2019;98:1071-82; Pemmaraju et al., Leuk Res. 2022;115:106809). We assessed the rate of arterial and venous TEs in a large cohort of low- and high-risk PV patients. Methods:We conducted a real-world, retrospective cohort study using Optum's de-identified Market Clarity Data, which includes electronic health records (EHR) on 105 million US patients between 2007-2019. Eligible patients were ≥18 years [yrs] old and required ≥2 PV diagnosis codes with ≥60 days between the first and last diagnosis code in the data period. Patients were indexed at the first diagnosis code of PV preceded by ≥1 year of EHR data (“index”) and required ≥1 year of post-index data or death prior to data period end (12/31/2019). Patients with a pre-index diagnosis of secondary polycythemia, leukemia, myelodysplastic syndrome, myelofibrosis, or stem cell transplant were excluded. Patients were stratified into three groups based on risk status at index: low-risk (age &amp;lt;60 without prior history of TE), age-based high-risk (age &amp;gt;60 without prior history of TE) and event-based high-risk (prior history of TE). As outcomes, TEs were identified at the first occurrence of a diagnosis code for a TE in EHR during the post-index period. Descriptive statistics were used to characterize the proportion of patients with TEs and event rates per 1000 PY. Kaplan-Meier analysis was used to evaluate the probability of TE-free survival among patients in the three risk groups at various time points. Patients were censored at death or last engagement date. Results:The total study cohort included 20,089 PV patients (mean age, 63.0 yrs; 57.8% male; 88.6% Caucasian). Approximately one-third (34.4%; 6909 patients) were low-risk, 49.4% (9924 patients) were age-based high-risk, and 16.2% (3256 patients) were event-based high-risk. Among 17,402 patients with pre-index medication data, 16.0% (n=2777) received hydroxyurea (HU) pre-index. HU usage was highest in age-based high-risk patients (21.8%) followed by event-based high-risk (20.0%) and low-risk patients (5.8%). Median follow-up period was 4.3 yrs (IQR, 2.4-5.9). Incidence of TEs was assessed within patient groups (Table 1). Overall, 25.1% (5035/20,089) of patients with PV experienced at least one TE during the post-index period. Incidence of TEs was highest among event-based high-risk patients (50.2%; 1634/3256), followed by age-based high-risk (25.0%; 2480/9924) and low-risk patients (13.3%; 921/6909). The rate of post-index TEs was more than triple for event-based high-risk patients vs. age-based high-risk patients (206 vs. 68/1000 PY) and nearly 7 times higher vs. low-risk patients (206 vs. 31/1000 PY). The rate of TEs was more than double for age-based high-risk patients vs. low-risk patients (68 vs. 31/1000 PY). Incidence of arterial and venous TEs was assessed across the total cohort (Table 1). The most common arterial events were stroke (7.1%) and MI/ACS (6.4%). The most common venous events were DVT/deep thrombophlebitis (8.1%) and pulmonary embolism (4.5%). Kaplan-Meier analysis indicated that at ≈2.5 yrs (1000 days) post-index, TE-free survival was ≈90% for low-risk, ≈80% for age-based high-risk, and ≈55% for event-based high-risk patients (Figure 1). At ≈5.5 yrs (2000 days) post-index, TE-free survival had fallen to ≈85% for low-risk, ≈70% for age-based high-risk, and ≈40% for event-based high-risk patients. The downward trend continued until the end of the data period. Conclusion: Findings from this real-world analysis indicate that PV patients experience high rates of arterial and venous TEs. Event-based high-risk patients have a substantially lower probability of TE-free survival compared with age-based high-risk and low-risk patients. While patients with a prior history of TE have the highest thromboembolic risk, all patients with PV are at high risk of TE, indicating an unmet need for reduction of thromboembolic risks.

Monoclonal Gammopathy of Undetermined Significance and the Risk of Thrombotic Events: Results from Istopmm, a Population-Based Screening Study in Iceland

Introduction: Multiple myeloma (MM), Waldenström's macroglobulinemia (WM), and related disorders have been associated with excess risk of thrombosis. Furthermore, medications used to treat these disorders, in particular immunomodulatory agents, have been associated with excess thrombotic risk. Monoclonal gammopathy of undetermined significance (MGUS), the asymptomatic precursor of MM, WM, and related disorders, has also been associated with arterial and venous thrombosis. However, prior studies have been based on cohorts where MGUS was diagnosed as part of the work-up for other unrelated medical disorders. We have shown that these cohort have biased selection of individuals with chronic disease, including autoimmune disease, heart failure, endocrine disorders and more. This selection bias may have led to false associations or overestimation of the relationship of MGUS and thrombotic events. Aim: To evaluate the relationship of MGUS and thrombosis in a screened cohort of individuals with MGUS. Methods: Data were obtained from the Iceland screens, treats, or prevents multiple myeloma study (iStopMM), a population-based screening study for MGUS and a randomized trial of follow-up strategies with the aim of evaluating the benefits and harms of MGUS screening. As part of the study 75,422 Icelandic residents 40 years and older (54% of the underlying population) have provided their informed consent for the study and were screened by serum protein electrophoresis (SPEP) and free light chain (FLC) assay. The cohort was crosslinked to population-based Icelandic government registries that includes all diagnoses made in the universal healthcare system, recorded as international classification of diseases (ICD) 10 codes. The study exposure was MGUS at screening and the outcome was venous and arterial thrombosis, defined as recorded ICD-10 codes. Events recorded within 90 days of each other were considered the same event. We further analyzed subgroups of M protein isotype and light chain (LC) MGUS. We followed participants prospectively after the date of screening to arterial and venous thrombosis as the endpoint and censoring at death, progression to MM, WM, and related disorders, or end of follow-up. Hazard ratios (HR) for time to first thrombotic event were estimated using Cox regression models, while hazard ratios for recurrent thrombotic events were estimated using mixed-effects Cox regression models with a random intercept. Both prospective analyses were adjusted for age as a non-linear variable and sex. In a secondary analysis, M-protein concentration was included as a non-linear variable into similar models that were restricted to those with MGUS with an M-protein. Results: Of the 75,422 screened, 3,353 had MGUS with an M-protein, here termed heavy chain (HC) MGUS, and 315 had LC MGUS. Over a median follow-up of 3.67 to 3.90 years, depending on the outcome of interest, 263 and 3,557 arterial events (20.4 and 13.5 per 1,000 person years) and 260 and 3,092 venous events (20.2 and 11.7 per 1,000 person years) were observed in those with and without MGUS respectively. MGUS was found to be associated with venous thrombotic events (HR: 1.31; 95% CI: 1.08-1.57), in particular deep vein thrombosis (HR:1.46; 95% CI: 1.12-1.90). Of the different MGUS subtypes, this association was only observed in non-IgM MGUS. The results were similar in the recurrent events analysis. IgM MGUS was found to be associated with a higher of peripheral arterial embolic events (HR: 2.86; 95% 1.04-7.85) but this association was not observed in the recurrent event analysis. M-protein concentration was not correlated with the risk of thrombotic events. Discussion: In this large population-based study including more than 75,000 individuals screened for MGUS, we found that MGUS, and particularly non-IgM MGUS, was associated with venous thrombotic events. Interestingly, the size of the M-protein spike was not associated with a higher risk for thromboembolic events. Further studies are needed to identify the underlying mechanisms with the goal of identifying subgroups of the MGUS population that may require interventions to prevent thrombotic events, potentially improving the survival and quality of life of those with MGUS.

Patients with atrial fibrillation and a low risk of thromboembolic events: prescription rate of anticoagulant therapy according to a retrospective analysis

Aim. To conduct a retrospective analysis of the prevalence of main risk factors for thromboembolic events (TEEs) and the prescription rate of anticoagulant therapy (ACT) in patients with atrial fibrillation (AF) and a low CHA2DS2-VASc score in certain Russian regions using artificial intelligence technologies.Material and methods. The information was obtained from the Webiomed predictive analytics platform. The sample included 87601 patients with AF aged 18-74 years (men, 49,5%, mean age, 59,3±12,3 years, mean CHA2DS2-VASc score, 2,3±1,5) who received care in medical organizations in 6 constituent entities of the Russian Federation in the period from 2016 to 2019. CHA2DS2VASc score of 1 and 2 in a man and a woman, respectively, was regarded as a moderate risk, while score of 0 and 1, respectively, as a low risk of TEEs.Results. There were 22337 (25,5%) patients with AF at moderate risk and 18366 (21,0%) patients at low risk of TEEs. With a moderate risk of TEEs, CHA2DS2-VASc score of 1 in 70,4% of cases was determined by hypertension, while in 15,7% — by age 65-74 years, in 9,0% — by heart failure, in 2,9% — by myocardial infarction and/or peripheral arterial disease, in 2,0% — by type 2 diabetes. In patients with AF and a moderate risk of TEEs, ACT was prescribed in 4927 (22,1%) patients, while with a low risk of TEEs — in 1833 (10,0%). Among patients with AF and a high risk of TEEs (n=46898, 53,5%), 1216 (24,6%) patients with ischemic stroke (IS) did not initially have a high CHA2DS2-VASc risk.Conclusion. In clinical practice, among patients with AF aged 18-74 years, there are quite often individuals with CHA2DS2-VASc score of 1 not associated with sex. These patients need an individualized approach in ACT, which is the basis for prospective studies in order to optimize the assessment of cardioembolic IS risk, as well as to analyze the efficacy and safety of long-term ACT.

Systemic Anticancer Therapy and Thromboembolic Outcomes in Hospitalized Patients With Cancer and COVID-19

Systematic data on the association between anticancer therapies and thromboembolic events (TEEs) in patients with COVID-19 are lacking. To assess the association between anticancer therapy exposure within 3 months prior to COVID-19 and TEEs following COVID-19 diagnosis in patients with cancer. This registry-based retrospective cohort study included patients who were hospitalized and had active cancer and laboratory-confirmed SARS-CoV-2 infection. Data were accrued from March 2020 to December 2021 and analyzed from December 2021 to October 2022. Treatments of interest (TOIs) (endocrine therapy, vascular endothelial growth factor inhibitors/tyrosine kinase inhibitors [VEGFis/TKIs], immunomodulators [IMiDs], immune checkpoint inhibitors [ICIs], chemotherapy) vs reference (no systemic therapy) in 3 months prior to COVID-19. Main outcomes were (1) venous thromboembolism (VTE) and (2) arterial thromboembolism (ATE). Secondary outcome was severity of COVID-19 (rates of intensive care unit admission, mechanical ventilation, 30-day all-cause mortality following TEEs in TOI vs reference group) at 30-day follow-up. Of 4988 hospitalized patients with cancer (median [IQR] age, 69 [59-78] years; 2608 [52%] male), 1869 had received 1 or more TOIs. Incidence of VTE was higher in all TOI groups: endocrine therapy, 7%; VEGFis/TKIs, 10%; IMiDs, 8%; ICIs, 12%; and chemotherapy, 10%, compared with patients not receiving systemic therapies (6%). In multivariable log-binomial regression analyses, relative risk of VTE (adjusted risk ratio [aRR], 1.33; 95% CI, 1.04-1.69) but not ATE (aRR, 0.81; 95% CI, 0.56-1.16) was significantly higher in those exposed to all TOIs pooled together vs those with no exposure. Among individual drugs, ICIs were significantly associated with VTE (aRR, 1.45; 95% CI, 1.01-2.07). Also noted were significant associations between VTE and active and progressing cancer (aRR, 1.43; 95% CI, 1.01-2.03), history of VTE (aRR, 3.10; 95% CI, 2.38-4.04), and high-risk site of cancer (aRR, 1.42; 95% CI, 1.14-1.75). Black patients had a higher risk of TEEs (aRR, 1.24; 95% CI, 1.03-1.50) than White patients. Patients with TEEs had high intensive care unit admission (46%) and mechanical ventilation (31%) rates. Relative risk of death in patients with TEEs was higher in those exposed to TOIs vs not (aRR, 1.12; 95% CI, 0.91-1.38) and was significantly associated with poor performance status (aRR, 1.77; 95% CI, 1.30-2.40) and active/progressing cancer (aRR, 1.55; 95% CI, 1.13-2.13). In this cohort study, relative risk of developing VTE was high among patients receiving TOIs and varied by the type of therapy, underlying risk factors, and demographics, such as race and ethnicity. These findings highlight the need for close monitoring and perhaps personalized thromboprophylaxis to prevent morbidity and mortality associated with COVID-19-related thromboembolism in patients with cancer.

Cost-effectiveness of ropeginterferon alfa-2b-njft for the treatment of polycythemia vera.

Aim: Patients with polycythemia vera (PV), a rare and chronic blood cancer, are at a higher risk for thromboembolic events, progression to myelofibrosis, and leukemic transformation. In 2021, ropeginterferon alfa-2b-njft (BESREMi®) was approved in the US to treat adults with PV. The purpose of this study is to estimate the cost-effectiveness of ropeginterferon alfa-2b-njft, used as a first- or second-line treatment, for the treatment of patients with PV in the US. Materials & methods: A Markov cohort model was developed from the healthcare system perspective in the United States. Model inputs were informed by the PROUD-PV and CONTINUATION-PV studies and published literature. The model population included both low-risk and high-risk patients with PV. The model compared ropeginterferon alfa-2b-njft used either as first- or second-line versus an alternative treatment pathway of first-line hydroxyurea followed by ruxolitinib. Results: Over the modeled lifetime, ropeginterferon alfa-2b-njft provided an additional 0.4 higher quality-adjusted life years (QALYs) and 0.4life-years with an added cost of USD60,175, resulting in a cost per QALY of USD141,783. The model was sensitive to treatment costs, the percentage of patients who discontinue hydroxyurea, the percentage of ropeginterferon alfa-2b-njft users who switch to monthly dosing, the percentage of ropeginterferon alfa-2b-njft users as 2nd line treatment, and the treatment response rates. A younger patient age at baseline and a higher percentage of patients with low-risk disease improved the cost-effectiveness of ropeginterferon alfa-2b-njft. Conclusion: Ropeginterferon alfa-2b-njft is a cost-effective treatment option for a broad range of patients with PV, including both low- and high-risk patients and patients with and without prior cytoreductive treatment with hydroxyurea.

Efficacy of different variants of endocardial balloon cryoablation in patients with persistent atrial fibrillation

Aim. To study the effectiveness of “extended” cryoballon ablation in patients with a persistent form of atrial fibrillation (AF) and to determine the risk factors for AF recurrence after cryoablation.Methods. The study included 89 patients (62±10 years, 24 [27%] men) with a persistent form of AF. The patients were randomized into two groups: in the 1st, the pulmonary veins (PV) cryoablation was performed (n=48 [53.9%]); in the 2nd, the PV cryoablation was performed in combination with cryoablation of the posterior wall of the left atrium (n=41 [46.1%]). The number of patients at high risk of thromboembolic events predominated in Group 2 (p=0,03). There is a high frequency of taking antiarrhythmic drugs of class III in this group (p=0.018). The follow-up period was 12 months. Clinical efficacy was assessed during a survey and daily ECG monitoring at face-to-face visits after 3, 6 and 12 months.Results. Antral isolation of PV was achieved in all 89 (100%) patients in both groups. In group 2, the average number of applications in the posterior wall of the PV was 10 [9; 13]. The effectiveness of cryoablation in group 1 by the end of the 12-month follow-up period was 54.2%, in group 2 - 56.1%. The complication rate (6.7%) in both groups did not differ statistically (p=0.683). The risk of arrhythmia recurrence didn’t depend on the strategy of cryoablation in postablation period (p=0.834). When conducting a single-factor analysis, a statistically significant effect on the probability of AF recurrence in the period of 3-12 months in group 1 was caused by AF recurrence in the blind period (95% confidence interval (CI): 1.5-27.7, p=0.013), in group 2 belonging to the female sex (95% CI: 1.2-24.6, p=0.032) and AF relapse in the blind period (95% CI: 1.5-128.5, p=0.020). During multivariate analysis in group 2, a statistically significant influence on the risk of AF recurrence in the period of 3-12 months was exerted by belonging to the female sex (hazard ratio (HR) 7.84; 95% CI 1478-42,23; p=0.016) and the presence of early AF recurrence (HR 20.36; 95% CI 1.99-208.23; p=0.011).Conclusion. Extended cryoablation in terms of efficiency and safety was comparable with the standard cryoablation. Early recurrence of AF (in the first 3 months after the intervention) turned out to be an independent risk factor for AF recurrence in the long-term period up to 12 months after cryoablation in both groups.

Aspirin is a safe and effective thromboembolic prophylaxis after total knee arthroplasty: a systematic review and meta-analysis.

Patients undergoing total knee arthroplasty (TKA) are at high risk for thromboembolic events compared to non-surgical patients. Both anticoagulants and antiplatelet agents are used as antithrombotic prophylaxis in TKA. The aim of this review is to understand the role of aspirin in the prevention of thromboembolic events and to compare its efficacy and safety with the main anticoagulants used in antithromboembolic prophylaxis in TKA. A systematic review and meta-analysis was performed according to the PRISMA guidelines. An electronic systematic search was conducted using PubMed, Scopus, and the Cochrane Central Registry to evaluate studies that compared aspirin with other anticoagulants, in terms of deep venous thrombosis and pulmonary embolism after TKA. The meta-analysis compared the rate of complications between aspirin and other anticoagulants. Thirteen studies were included in the systematic review for a total of 163,983 patients, and 10 studies were included in the meta-analysis. The meta-analysis demonstrated no statistically significant differences between aspirin and other anticoagulants in terms of the rate of deep venous thrombosis (OR 0.93, 95% CI 0.81-1.08, p = 0.35) and pulmonary embolism (OR 0.89, 95% CI 0.56-1.41, p = 0.61). Aspirin is safe, effective, and not inferior to other main anticoagulants in preventing thromboembolic events following TKA.

Identifying Patients with Polycythemia Vera at Risk of Thrombosis after Hydroxyurea Initiation: The Polycythemia Vera-Advanced Integrated Models (PV-AIM) Project.

Patients with polycythemia vera (PV) are at significant risk of thromboembolic events (TE). The PV-AIM study used the Optum® de-identified Electronic Health Record dataset and machine learning to identify markers of TE in a real-world population. Data for 82,960 patients with PV were extracted: 3852 patients were treated with hydroxyurea (HU) only, while 130 patients were treated with HU and then changed to ruxolitinib (HU-ruxolitinib). For HU-alone patients, the annualized incidence rates (IR; per 100 patients) decreased from 8.7 (before HU) to 5.6 (during HU) but increased markedly to 10.5 (continuing HU). Whereas for HU-ruxolitinib patients, the IR decreased from 10.8 (before HU) to 8.4 (during HU) and was maintained at 8.3 (after switching to ruxolitinib). To better understand markers associated with TE risk, we built a machine-learning model for HU-alone patients and validated it using an independent dataset. The model identified lymphocyte percentage (LYP), neutrophil percentage (NEP), and red cell distribution width (RDW) as key markers of TE risk, and optimal thresholds for these markers were established, from which a decision tree was derived. Using these widely used laboratory markers, the decision tree could be used to identify patients at high risk for TE, facilitate treatment decisions, and optimize patient management.

#4654 THROMBOEMBOLIC EVENTS AND THEIR RELATIONSHIP WITH COVID-19 IN HEMODIALYSIS PATIENTS: MYTH OR TRUE ?

Abstract Background and Aims Since the beginning of COVID-19 pandemic, there has been more than 668 million of diagnosis and more than 6 million deaths worldwide. This pandemic also has had a dramatic impact on chronic patients, such as those with end stage renal disease (ESRD) on hemodialysis (HD). Many studies have hypothesized that COVID-19 could induce a hypercoagulability state, activating coagulation cascade. Post-mortem studies revealed vascular injuries in more than 60% of lung tissues and many patients diagnosed with COVID-19 have suffered neurological pathologies, as ischemic stroke. Patients with ESRD are also at higher risk of thromboembolic events than healthy subjects. In this study, we analyze thromboembolic events in HD patients with or without COVID-19 diagnosis. Method We performed a retrospective observational study between March 2020 and December 2022 with 4679 HD patients (2635 COVID-19 positive patients (Group 1) and 2044 COVID-19 negative (Group 2)) from 50 Spanish clinics. The baseline dates of the non COVID-19 patients were randomly chosen. Follow-up time was 1 year since COVID-19 diagnosis (Group 1) or since selection (Group 2). We identified patients who has suffered any thromboembolic event during follow-up time. We compared usual clinical parameters between groups using Chi2 and Mann-Whitney U tests. Survival analysis was performed by Kaplan-Meier and Cox regression. Continuous variables were categorized to perform the Cox analysis. Results Small differences between Group 1 and 2 were found in age (70.45 (62-81) vs 68.94 (61-80); p&amp;lt;0.001), proportion of men (63% vs 67.2%; p&amp;lt;0.05), HD vintage (34 (14-71) vs 30 (11-65); p&amp;lt;0.05), preHD systolic blood pressure (SBP) (140.73 (126-155) vs 142.65 (128-157); p&amp;lt;0.05), plasma hemoglobin (Hb) (11.19 (10.40-11.90) vs 11.31 (10.5-12); p&amp;lt;0.05) and proportion of patients with antithrombic medication (604 (22.9%) vs 401 (19.6%); p&amp;lt;0.05). No statistically significant differences were found in time to first thromboembolic event between the two groups (Figure 1). In univariate Cox regression (Table 1) thromboembolic events showed significant relation with gender, Charlson Index above 8, preHD relative overhydration (relOH) above 13.4% and preHD SBP above 155 mmHg. In multivariate analysis (Table 1), Charlson Index and preHD SBP showed hazard ratio above 1.5 for thromboembolic event (p&amp;lt;0.05). COVID-19 diagnosis did not show relationship with thromboembolic events. Conclusion Publications on thromboembolic events in HD patients who have suffered from COVID-19 are scarce and with small size samples. In our large HD sample, thromboembolic events were not related to COVID-19. Only Charlson Index and preHD SBP showed a significant relationship in the multivariate analysis.

Thrombosis in the Neonatal Intensive Care Unit.

Neonates, particularly critically ill and premature infants, have one of the highest risks of thromboembolic complications, particularly venous thromboembolism (VTE), in the pediatric population. Recent data suggest that the incidence of VTE has significantly increased in neonates over the last few decades. Critically ill and premature infants exhibit multiple risk factors that place them at a high risk for thromboembolic events including developmental hemostasis, propensity to infections, and frequent need for central venous access. The clinical presentation, diagnostic modalities, and treatment strategies for thromboembolic complications in neonates vary based on several factors, including the etiology of the thromboembolic event, the anatomic site affected, and the patient's underlying comorbidities. Although guidelines for management are available, they are mostly based on consensus recommendations and on extrapolation from adult data due to a lack of high-quality data in the neonatal population. Current guidelines recommend anticoagulation for specific scenarios. More studies are necessary to elucidate optimal management strategies for newborns with thromboembolic complications.

Extra-cranial hemorrhagic complications in patients with COVID-19 infection: the experience of a secondary care COVID-19 institution

BACKGROUND: COVID-19 patients are considered to be at high risk for thromboembolic events, and are subjected to large doses of anticoagulants. However, the associated risk of major bleeding remains underestimated. The aim of this study was to investigate extracranial major bleeding complications in a cohort of critically ill patients with COVID-19 pneumonia, diagnosed with computed tomography (CT) or magnetic resonance (MR), and to examine their relationship with laboratory data and pro-thrombothic status.METHODS: In this retrospective observational study, patients admitted to a single secondary care center from November 1, 2020 and January 31, 2022, who tested positive for COVID-19 and developed significant anemia (reduction in Hb levels >2 g/dL) over the course of hospitalization were included. Clinical-laboratory parameters and imaging were reviewed.RESULTS: Out of 279 patients, hemorrhagic complications were detected in 18 patients (10 males, 8 females, mean age 78.6 years, range 63-89 years), with CT evidence of atraumatic bleedings in the thoraco-abdominal wall (N.=8, bilaterally in one case), in the thoracic cavity (N.=2), in the iliopsoas compartment (N.=5), and in the intestinal lumen (N.=1). Intra-articular (N.=1) and intraspinal (N.=1) hematomas were also found. 14/18 patients underwent angiographic embolization. Three patients simultaneously showed pulmonary embolism.CONCLUSIONS: Spontaneous major extracranial bleeding, at the thoraco-abdominal level and in other atypical sites, represents a rare but serious complication of COVID-19 infection and must always be considered in case of anemia during the course of the disease and relative hospitalization.

Management of oral anticoagulant therapy after intracranial hemorrhage in patients with atrial fibrillation.

Intracranial hemorrhage (ICH) is considered a potentially severe complication of oral anticoagulants (OACs) and antiplatelet therapy (APT). Patients with atrial fibrillation (AF) who survived ICH present both an increased ischemic and bleeding risk. Due to its lethality, initiating or reinitiating OACs in ICH survivors with AF is challenging. Since ICH recurrence may be life-threatening, patients who experience an ICH are often not treated with OACs, and thus remain at a higher risk of thromboembolic events. It is worthy of mention that subjects with a recent ICH and AF have been scarcely enrolled in randomized controlled trials (RCTs) on ischemic stroke risk management in AF. Nevertheless, in observational studies, stroke incidence and mortality of patients with AF who survived ICH had been shown to be significantly reduced among those treated with OACs. However, the risk of hemorrhagic events, including recurrent ICH, was not necessarily increased, especially in patients with post-traumatic ICH. The optimal timing of anticoagulation initiation or restarting after an ICH in AF patients is also largely debated. Finally, the left atrial appendage occlusion option should be evaluated in AF patients with a very high risk of recurrent ICH. Overall, an interdisciplinary unit consisting of cardiologists, neurologists, neuroradiologists, neurosurgeons, patients, and their families should be involved in management decisions. According to available evidence, this review outlines the most appropriate anticoagulation strategies after an ICH that should be adopted to treat this neglected subset of patients.

Factors determining adherence to anticoagulant therapy in patients with atrial fibrillation

Aim. To identify risk factors for low adherence and develop a scale for its pre­diction. To evaluate the association of the predictive score with actual low adherence according to the 8-item Morisky Medication Adherence Scale, self-drug withdrawal, and adverse outcomes in patients with atrial fibrillation (AF).Material and methods. The study included patients with AF and a high risk of thromboembolic events according to the CHA2DS2-VASc scale, who were hospitalized from January 2011 to December 2017. Potential risk factors for non-adherence, selected from the literature, were tested in a multivariate regression analysis followed by the development of an adherence prediction scale. The asso­ciation of predicted low adherence with actual adherence was assessed.Results. The study included 199 patients. The analysis identified following predictors of low adherence: low income, history of bleeding, prior stroke, 4 positive responses to the adherence questionnaire, warfarin. Based on these predictors, a scale for predicting adherence was developed, while a threshold value of 3 points was identified (sensitivity, 90,2%, specificity, 98,4%). A significant association of low predicted adherence on the developed scale with actual adherence and adverse outcomes was demonstrated.Conclusion. We have developed a scale for predicting adherence to anticoagulant therapy, and also determined its threshold value. In case of a high risk of low adherence, clinicians should try to increase adherence in order to prevent comp­lications.

Stroke Prevention With Left Atrial Appendage Closure in Patients With Atrial Fibrillation and Prior Intracranial Hemorrhage

BackgroundOral anticoagulation (OAC) is deemed a relative contraindication after intracranial hemorrhage (ICH) if the cause cannot be eliminated and the risk of recurrence is high. That leaves atrial fibrillation (AF) patients at high risk of thromboembolic events. Endovascular left atrial appendage closure (LAAC) can be an alternative to OAC for patients requiring stroke prevention. MethodsWe performed a retrospective single-centre analysis of 138 consecutive ICH patients with nonvalvular AF and high stroke risk who underwent LAAC between 2010 and 2022 at Vancouver General Hospital. We report the baseline characteristics, procedural results, and follow-up data, comparing the observed stroke/transient ischemic attack (TIA) rate with the predicted event rate based on their CHA2DS2-VASc scores. ResultsThe average age was 76.1 ± 8.5 years; the mean CHA2DS2-VASc score was 4.4 ± 1.5; and the mean HAS-BLED score was 3.7 ± 0.9. The procedural success rate was 98.6%, and the complication rate was 3.6% with no periprocedural death, stroke, or TIA. The antithrombotic regimen post-LAAC consisted of short-term dual antiplatelet therapy (1-6 months) followed by aspirin alone for a minimum of 6 months in 86.2%. At mean follow-up of 14.7 ± 13.7 months, 9 deaths (6.5%, 7 cardiovascular, 2 noncardiovascular), 2 strokes (1.4%), and 1 TIA (0.7%) had occurred. The annualized observed stroke/TIA rate was 1.8%, which was lower than the adjusted predicted stroke rate of 7.0% (95% confidence interval: 4.8%-9.2%). Two patients (1.5%) suffered another ICH (both on aspirin monotherapy). One device-related thrombus (0.7%) was confirmed and treated with OAC without sequelae. ConclusionEndovascular LAAC is a feasible alternative to OAC for stroke prevention in patients with nonvalvular AF and prior ICH.

P-wave parameters and their association with thrombi and spontaneous echo contrast in the left atrial appendage.

The aim of this study was to examine the prevalence of abnormal P-wave parameters in patients with thrombus and/or spontaneous echo contrast (SEC) in the left atrial appendage (LAA), and to identify P-wave parameters particularly associated with thrombus and SEC formation. We presume a significant relationship of P-wave parameters with thrombi and SEC. All patients in whom a thrombus or SEC was detected in the LAA on transoesophageal echocardiography were included in this study. Patients at risk (CHA2DS2-VASc Score ≥3) and routine transoesophageal echocardiography to exclude thrombi served as the control group. A detailed ECG analysis was performed. Of a total of 4062 transoesophageal echocardiographies, thrombi and SEC were detected in 302 patients (7.4%). Of these patients, 27 (8.9%) presented with sinus rhythm. The control group included 79 patients. There was no difference in mean CHA2DS2-VASc score in the two groups (p = .182). A high prevalence of abnormal P-wave parameters was detected in patients with thrombus/SEC. Indicators for the presence of thrombi or SEC in the LAA were P-wave duration >118 ms (Odds ratio (OR) 3.418, Confidence interval (CI) 1.522-7.674, p < .001), P-wave dispersion >40 ms (OR 2.521, CI 1.390-4.571, p < .001) and advanced interatrial block (OR 1.431, CI 1.033-1.984, p = .005). Our study revealed that several P-wave parameters are associated with thrombi and SEC in the LAA. The results may help identify patients who are at particularly high risk for thromboembolic events (e.g.,in patients with embolic stroke of undetermined source).