Chronic Anticoagulation Research Articles

Diagnostic pitfalls in child thrombosis

In recent years, we have seen an increase in thrombotic events in children, which creates difficulties in early diag­no­sis, especially in rare locations such as portal vein throm­bo­sis. The most common cause is represented by an­ti­phos­pho­lipid syndrome (APS), especially secondary to systemic lupus erythematosus (SLE). The investigation of the prothrombophilic pattern is mandatory in these pa­tients, the association being possible. The therapeutic ma­nage­ment is complex, in a multidisciplinary team, and will in­clude, in addition to chronic anticoagulation, an effective im­mu­no­sup­pression to control the degree of activity of the lupus disease.

Predictors and outcomes of respiratory failure among lung transplant patients with COVID-19.

BackgroundThere is limited data on the predictors and outcomes of new or worsening respiratory failure among lung transplant (LT) patients with Coronavirus disease 2019 (COVID‐19).MethodsWe included all the LT patients diagnosed with COVID‐19 during a 1‐year period (March 2020 to February 2021; n = 54; median age: 60, 20–73 years; M:F 37:17). Development of new or worsening respiratory failure (ARF) was the primary outcome variable.ResultsThe overall incidence of ARF was 48.1% (n = 26). More than 20% of patients (n = 11) needed intubation and mechanical ventilation. Body mass index > 25 Kg/m2 (adjusted OR: 5.7, .99–32.93; P = .05) and peak D‐dimer levels > .95 mcg/ml (adjusted OR: 24.99, 1.77–353.8; P = .017) were independently associated with ARF while anticoagulation use prior to COVID‐19 was protective (adjusted OR: .024, .001–.55; P = .02). Majority patients survived the acute illness (85.2%). Pre‐infection chronic lung allograft dysfunction (CLAD) was an independent predictor of mortality (adjusted HR: 5.03, 1.14–22.25; P = .033).ConclusionsCOVID‐19 is associated with significant morbidity and mortality among LT patients. Patients on chronic anticoagulation seem to enjoy favorable outcomes, while higher BMI and peak D‐dimer levels are associated with development of ARF. Pre‐infection CLAD is associated with an increased risk of death from COVID‐19.

Pre- and in-hospital anticoagulation therapy in coronavirus disease 2019 patients: a propensity-matched analysis of in-hospital outcomes.

To estimate if chronic anticoagulant (CAC) treatment is associated with morbidity and mortality outcomes of patients hospitalized for SARS-CoV-2 infection. In this European multicentric cohort study, we included 1186 patients of whom 144 were on CAC (12.1%) with positive coronavirus disease 2019 testing between 1 February and 30 July 2020. The average treatment effect (ATE) analysis with a propensity score-matching (PSM) algorithm was used to estimate the impact of CAC on the primary outcomes defined as in-hospital death, major and minor bleeding events, cardiovascular complications (CCI), and acute kidney injury (AKI). We also investigated if different dosages of in-hospital heparin were associated with in-hospital survival. In unadjusted populations, primary outcomes were significantly higher among CAC patients compared with non-CAC patients: all-cause death (35% vs. 18% P < 0.001), major and minor bleeding (14% vs. 8% P = 0.026; 25% vs. 17% P = 0.014), CCI (27% vs. 14% P < 0.001), and AKI (42% vs. 19% P < 0.001). In ATE analysis with PSM, there was no significant association between CAC and primary outcomes except for an increased incidence of AKI (ATE +10.2%, 95% confidence interval 0.3-20.1%, P = 0.044). Conversely, in-hospital heparin, regardless of dose, was associated with a significantly higher survival compared with no anticoagulation. The use of CAC was not associated with the primary outcomes except for the increase in AKI. However, in the adjusted survival analysis, any dose of in-hospital anticoagulation was associated with significantly higher survival compared with no anticoagulation.

Loss of engagement in controlling chronic anticoagulation therapy during Covid-19 stringency measures. A single center experience of disproportioned increase of stuck mechanical valves.

Stuck valve is a very rare and severe complication that occurs in mechanical valve replacement patients with ineffective anticoagulation. However, with COVID-19 restriction measures, it became challenging to regularly assess INR to make sure it falls within the target therapeutic range to prevent this complication. We present a series of 10 patients who either underwent transthoracic echocardiography for a suspected stuck valve or were seen at the outpatient valve clinic with the residual consequences of a stuck valve during the COVID-19 restriction measures in our institute. Stuck prosthetic valves incident has increased significantly during this period, particularly those in the mitral position for which urgent replacement and prolonged hospitalization were necessary. Particularly with the COVID-19 restrictions in place, these cases highlight the need for physicians to be aware of the dramatic increase in the incidence of stuck prosthetic valves in patients on chronic warfarin therapy.

Clopidogrel or ticagrelor alongside dabigatran in acute coronary syndrome and indication for NOAC: a study rationale.

The combination of oral anticoagulants with platelet inhibitors has been widely investigated in patients with coronary stenting and concomitant atrial fibrillation. In these patients, default therapy after percutaneous coronary intervention in acute coronary syndrome is clopidogrel plus non-vitamin K antagonist oral anticoagulant, omitting aspirin. However, in view of the high thromboembolic risk associated with acute coronary syndrome and the number of poor metabolizers for clopidogrel, investigation of alternative P2Y12-inhibitors is mandatory. This prospective, multicenter, open-label, registry-based, randomized, controlled trial aims to show the non-inferiority of dabigatran plus ticagrelor versus dabigatran plus clopidogrel in patients on chronic anticoagulants who undergo percutaneous coronary intervention in acute coronary syndrome. The primary end point is major bleeding as defined by the Bleeding Academic Research Consortium bleeding definition. Trial registration number: NL75644.096.21.

Abstract 11915: Less Aspirin, Less Bleeding for Patients on Chronic Warfarin Anticoagulation for Atrial Fibrillation and/or Venous Thromboembolic Disease

Introduction: For some patients on chronic warfarin anticoagulation for atrial fibrillation and/or venous thromboembolic disease, the addition of aspirin (ASA) may increase bleeding with uncertain therapeutic benefit. Between 2017 and 2018, the six-center Michigan Anticoagulation Quality Improvement Initiative implemented a multi-center quality improvement project to reduce excess aspirin use. Hypothesis: We anticipated reductions in overall ASA use and bleeding. Methods: Warfarin treated patients taking ASA without a clear indication (eg. coronary artery disease) were identified. Their primary care provider was contacted to advise if ongoing ASA+warfarin was recommended. ASA was discontinued if suggested by their doctor. Data was abstracted by trained abstractors using predefined forms. In December 2019, we evaluated monthly rates of excess ASA use, bleeding, and thrombotic outcomes. Data were analyzed using piecewise linear regression. Results: We followed 6,738 patients for a median (interquartile range) of 6.7 months (3.2-19.3 months). Aspirin use declined significantly over the 24 months before our intervention (P&lt;0.001) with an accelerated decline post intervention (p=0.001, Figure 1). Our intervention was associated with a non-significant decline in bleeding (p=0.12), emergency room (ER) visits for bleeding (p=0.35), admissions for bleeding (p=0.97), a significant decline in major bleeding (p=0.029), and no significant change in thrombotic outcomes (p=0.34). Including the decline in ASA use starting 24 months pre-intervention, reducing ASA use resulted in significant declines in any bleeding, major bleeding, and ER visits for bleeding (p=0.021, p=0.001, p=0.038 respectively). There remained no change in thrombotic outcomes (p=0.36). Conclusions: Our quality improvement intervention reduced aspirin use. Reductions in aspirin use were associated with reduced bleeding outcomes without increased thrombotic outcomes.

Postprocedural Radial Artery Compression Time In Chronic AnticoaguLated patients using StatSeal: The PRACTICAL-SEAL study

BackgroundPatients on uniterrupted chronic oral anticoagulation (OAC) therapy are at high-risk of bleeding during cardiac catheterization. We aimed to investigate the safety and efficacy of the StatSeal® disc for adjunct hemostasis in patients undergoing transradial coronary angiography under uninterrupted OAC therapy. MethodsPatients who underwent transradial cardiac catheterization without interrupted OAC therapy were included in this study. ResultsAmong 180 patients, 85 (47.2%) patients were on warfarin and 95 (52.8%) patients on novel oral anticoagulants (NOACs). Patients on NOACs were older (72.9 ± 9.6 versus 69.7 ± 10.8 years, P < 0.001) and had more atrial fibrillation/flutter (94.7% versus 62.4%, P < 0.001), whereas patients on Warfarin were more often women (43.5% versus 26.3%, P = 0.02) and had mechanical heart valves (27.1% versus 0%, P < 0.001). Intravenous unfractioned heparin (UFH) was administered in 96.5% of patients on warfarin (3799 ± 1342 units) and 93.7% patients on NOACs (4028 ± 1362 units), P = 0.27. There were no differences in terms of type and sheath size and the need for ad hoc coronary intervention. Time-to-first release of the hemostatic wristband was 56.2 ± 12.6 min and complete hemostasis was achieved in 71.1 ± 13.0 min, with shorter times among patients on NOACs (54.1 ± 11.7 and 58.5 ± 13.2 min, 68.9 ± 11.7 versus 73.6 ± 14.0 min, P = 0.02, for both). There were no significant differences in terms of bleeding. There was no radial artery occlusion among 112 participants who underwent color Doppler ultrasound. ConclusionThe present study shows that in patients undergoing transradial coronary angiogram under contemporary uninterrupted OAC therapy and periprocedural administration of UFH, the use of StatSeal® disc for adjunctive hemostasis was associated with short times to complete hemostasis.

The Impact of Degree of Anticoagulation on Thrombotic and Other Complications in Hospitalized COVID-19 Patients

Introduction:In hospitalized patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the frequency of venous thromboembolism (VTE) is increased. Retrospective studies suggested that an elevated D-dimer level is associated with increased mortality and predictive of thrombosis in these patients. In the spring of 2020, our institution developed a risk protocol for stratification of hospitalized COVID-19 patients into high, intermediate, or low risk groups, based upon history of thrombosis and D-dimer level. These patients were treated with full-dose anticoagulation, high- or standard-dose prophylaxis, respectively. The goal of this project was to determine the impact of this protocol on VTE frequency, need for intensive care unit (ICU) admission, organ failure and in-hospital mortality while assessing the frequency of hemorrhagic complications when compared to standard prophylactic anticoagulation.Methods:We performed a retrospective chart review of adults hospitalized between March 1 - June 1, 2020 who tested positive for SARS-CoV-2 by nasopharyngeal polymerase chain reaction (PCR). Patients were excluded if they were initially admitted to the ICU. VTE was defined as either a deep vein thrombosis (DVT) on Duplex ultrasound and/or pulmonary embolism (PE) on computed tomography (CT) angiogram. We collected demographic data, medical histories, laboratory and radiologic data on all subjects. Data were analyzed using the Chi Square test and Fisher's Exact Test to establish significant association with clinical outcomes between 3 anticoagulation regimens. Statistical significance was assessed at the p<0.05 level.Results:Data were analyzed from 910 patients; 496 (54.6%) were male and the mean age was 57.8 ± 16.9 years. 419 (46%) subjects were Black, 151 (16.6%) Caucasian, 133 (14.6%) Latinx. Diabetes mellitus (35.3%) and hypertension (59.8%) were common in our cohort as were tobacco (12.6%) and alcohol (20.4%) use. Only 69 (7.6%) were treated with chronic anticoagulation and 216 (23.7%) were on antiplatelet agents. 123 (13.5%) required an ICU transfer and the overall mortality was 5.3%. Most patients, 809 (88.9%), received standard prophylactic anti-coagulation initially (Group A); 32 (3.5%) received high dose prophylaxis (Group B) and 69 (7.6%) received therapeutic dose anticoagulation (Group C). In the entire cohort, 46 (5.1%) developed VTE; 29 (3.6%) in Group A, 2 (6.3%) in Group B, and 15 (22%) in Group C (p<0.0001). ICU admission was required for 102 (12.6%) in Group A, 7 (21.9%) in Group B, and 14 (20.3%) in Group C (p=0.075). 73 ICU patients (8%) required vasopressors, including 57 (7%) in Group A, 6 (18.8%) in Group B and 10 (14.5%) in Group C (p=0.175). 81 ICU patients (8.9%) required mechanical ventilation, including 66 (8.2%) in Group A, 6 (18.8%) in Group B, and 9 (13%) in Group C (p=0.513). One patient in Group B developed an intracerebral hemorrhage. Gastrointestinal hemorrhage occurred in 11 (1.2%) of the cohort; similar rates were observed across treatment arms. The overall in-hospital mortality was 5.3% in this cohort (4.7% in Group A, 12.5% in Group B, and 8.6% in Group C, p=0.064).Conclusion:The rate of VTE in COVID-19 patients receiving any form of anti-coagulation was low. There was an increased rate of VTE, but not rates of ICU admission, mortality, mechanical ventilation nor vasopressor use in those receiving either high dose prophylaxis or therapeutic anticoagulation, suggesting an increased propensity for thrombosis either related to prior thrombotic events or reflected by increased D-dimer levels. These findings need to be confirmed in prospective studies. DisclosuresDiLorenzo: Abbott: Current holder of individual stocks in a privately-held company; Merck & Co: Current holder of individual stocks in a privately-held company; Glaxo Smith Kline: Current holder of individual stocks in a privately-held company. Sloan: Pharmacosmos: Membership on an entity's Board of Directors or advisory committees; Astra Zeneca: Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria; Stemline: Honoraria. Weinberg: Janssen Pharmaceuticals: Other: Serve on data safety monitoring boards; Merck & Co: Current holder of individual stocks in a privately-held company. Klings: CSL Behring: Other: Consultant; Omeros: Other: Consultant; Bluebird Bio: Other: Consultant; Bayer: Research Funding; Novartis: Research Funding; FORM therapeutics: Research Funding.

Results of the International Survey on Adherence with Anticoagulation in Children, Adolescents and Young Adults

IntroductionChildren, adolescents, and young adults are prescribed chronic anticoagulation with oral and parenteral medications for treatment and prevention of thrombosis. Non-adherence to the recommended dosing, schedule, and monitoring of anticoagulants may lead to poor treatment outcomes. Considering that little is known about adherence to anticoagulation in children, this survey aimed to evaluate provider practices and experiences related to pediatric, adolescent, and young adult patient adherence with anticoagulation.MethodsA REDCap ® survey was developed by members of the International Haemostasis and Thrombosis Pediatric and Neonatal Scientific Subcommittee Medication Adherence Working Group. Questions regarding current clinical practices related to medication adherence (i.e., assessment, barriers to addressing adherence) were developed by the multi-disciplinary working group with expertise in anticoagulation, medication adherence, and hematology research. The survey was distributed in electronic form to more than 500 clinicians through the International Society of Haemostasis and Thrombosis plus related professional organizations in the United States, Switzerland, New Zealand, and Australia. Clinicians are eligible for the study if they are involved in anticoagulation management in children and/or adolescents and young adults.ResultsA total of 112 clinicians completed surveys. The majority (n = 104 , 93%) were pediatric hematology/oncology physicians. Demographic and clinical practice characteristics are shown in Table 1. Ninety-nine (88%) respondents reported that medication adherence is typically assessed for patients in their practice prescribed anticoagulation. Details regarding medication adherence clinical practices are shown in Table 2. Forty-eight (43%) reported that they often or always worry about medication adherence in patients prescribed anticoagulation. While most clinicians (n = 83, 74%) reported they are often or always confident in addressing non-adherence, only 30% (n = 34) reported that they are often or always confident about identifying patients who are non-adherent and only 50 (45%) reported that they often or always have the resources to effectively address non-adherence. Fifty-five (49%) respondents indicated that they had cases where non-adherence resulted in new or recurrent thrombosis and 20 (18%) indicated that they had cases where non-adherence resulted in bleeding. In response to the free text question: “What types of resources would make it easier to measure adherence in your clinic?,” themes emerged regarding tools (i.e., validated instruments and electronic apps to measure adherence), communication with pharmacy, and more time and staffing in clinic. When asked: “When you identify a patient/family who is struggling to take their anticoagulation as prescribed or follow-up with labs or appointments for anticoagulation, what do you do?,” clinicians discussed identification of barriers; education; involving additional staff including nursing, social work, and pharmacy; consider switching anticoagulation; increase frequency of calls, clinic visits and/or labs; and use of reminders. Some providers reported utilizing shared decision-making or motivational interviewing to improve adherence.ConclusionsClinicians who prescribe anticoagulation for children, teens, and young adults identify medication non-adherence as a clinically significant issue that may result in recurrent thrombosis or bleeding. Clinicians perceive that non-adherence most often occurs when patients skip doses and/or do not follow monitoring recommendations. Current gaps in clinical practice include resources to identify patients who are non-adherent and strategies to improve adherence. A multi-disciplinary team including nurses, physicians, pharmacists, social workers, and psychologists who have dedicated time for anticoagulation management could potentially improve outcomes for children prescribed anticoagulation. As direct oral anticoagulants are approved for children and adolescents, the impact on medication adherence with these treatment options should be evaluated. [Display omitted] DisclosuresThornburg: HemaBiologics: Honoraria; CSL Behring: Honoraria; Octapharma: Honoraria; Biomarin: Honoraria, Research Funding; Genentech: Honoraria; Bluebird Bio: Other: data safety monitoring board; Ironwood Pharmaceuticals: Other: data safety monitoring board.

A Treacherous Twist on ECG

The patient is a 61-year-old female with a history of well-controlled hypothyroidism on levothyroxine supplementation and prior suspected cardioembolic stroke on chronic anticoagulation who previously underwent surgical mitral valve repair 1 year previously due to symptoms of severe fatigue with a baseline left ventricular ejection fraction of 55%-60% and nonobstructive coronary artery disease. Immediately following surgery, her left ventricular ejection fraction declined to 40%. Postoperatively, she continued to experience fatigue with gradual worsening of her left ventricular ejection fraction to 30%.

The Comparative Effectiveness and Safety of Different Anticoagulation Strategies for Treatment of Left Atrial Appendage Thrombus in the Setting of Chronic Anticoagulation for Atrial Fibrillation or Flutter

PurposeTo compare effectiveness of different treatments for atrial fibrillation (AF) patients who were scheduled for cardioversion (CV) or ablation (CA) presenting with left atrium appendage (LAA) thrombus despite chronic oral anticoagulation therapy (OAC).MethodsThis was a retrospective cohort study. We analyzed 2014–2019 medical records of patients scheduled for CV or CA of AF who were diagnosed with LAA thrombus despite optimal OAC and had a follow-up transesophageal echocardiogram (TOE). Changes in treatment were divided into the following groups: switch to a drug with different mechanism of action, switch to a drug with similar mechanism of action, initiation of combination therapy, or deliberate no change in treatment. Patients with contraindications to non-vitamin K antagonists were excluded from the analysis.ResultsWe analyzed data of 129 patients comprising 181 cycles of treatment. The overall effectiveness of LAA thrombus dissolution was 51.9% regardless of the number of cycles and 42.6% for the first cycle of treatment. Any change of treatment was more effective than deliberate no change—OR 2.97 [95% CI: 1.07–8.25], P = 0.031, but no particular strategy seemed to be more effective than the other. Left atrium area (OR 0.908 [95% CI: 0.842–0.979]) and number of treatment cycles (OR 0.457 [95% CI: 0.239–0.872]) were both adversely related to thrombus resolution. There was one ischemic and three bleeding adverse events during the treatment.ConclusionLAA thrombus resolution in patients already on OAC may require a change of previous OAC treatment but the overall effectiveness of dissolution seems to be about 50%.

Coronary artery calcium in patients with atrial fibrillation undergoing catheter ablation – an opportunity to personalize cardiovascular and thromboembolic risk management

Abstract Introduction There is a well-established association between atrial fibrillation (AF) and coronary artery disease (CAD). Coronary artery calcium score (CACS) is a helpful tool to refine cardiovascular risk stratification and guide strategies of cardiovascular (CV) primary prevention. Purpose To evaluate the prevalence and clinical implications of CACS in terms of CV and thromboembolic risk stratification and preventive therapies, in patients with AF and atrial flutter (AFL) undergoing catheter ablation. Methods Cross-sectional study including patients with AF/AFL undergoing multidetector computed tomography (MDCT) for ablation procedure planning from 2017 to 2019. Baseline clinical and demographical data were collected. CV and thromboembolic risks were evaluated based on the SCORE (Systematic Coronary Risk Evaluation) system and CHA2DS2-VASc score. CACS was assessed in patients without history of coronary artery disease using the Agatston method. Results A total of 474 patients were included (441 with AF and 33 with AFL, mean age of 58±10 years, 62% male). Excluding those over 70 years of age (n=50, 11%), most patients had low (n=69, 22%) or moderate (n=188, 60%) CV risk and 277 (64%) patients had a CHA2DS2-VASc score ≥1 (male) or ≥2 (female). Overall, 265 patients (65%) were under chronic anticoagulation and 157 (39%) were under statin therapy. CAC was present in 254 (54%) patients and showed a multivessel distribution in 62% of the cases. The left main stem was affected in 81 (17%) patients and the left anterior descending artery in 211 (45%). Incorporating CACS&amp;gt;100 as a variable in CHA2DS2-VASc score (vascular disease parameter in patients without history of vascular disease) would have resulted in a significant score reclassification (n=87, 20%) and identification of new potential candidates for anticoagulation (n=12, 3%). Additional, anticoagulation would be indicated as a class IA recommendation in more 26 (6%) patients. Twenty three percent of patients with zero calcium were taking statins, and only 7% of patients with a CACS &amp;gt;300 were on high-intensity statin therapy. According to the recommendations and based on their CACS and current therapy, 103 (25%) patients would be candidates for statin therapy and 69 (17%) patients would be candidates for changes in the current statin therapy intensity (Table 1). Conclusion In our study, more than half of the patients undergoing MDCT before AF/AFL catheter ablation had coronary calcium above zero. Our findings suggest that an opportunistic evaluation of CACS can be clinically valuable in thromboembolic risk stratification and management of preventive pharmacological strategies such as anticoagulation and statins. Funding Acknowledgement Type of funding sources: None.

Bioabsorbable vascular scaffolds in routine practice: long-term results

Abstract Background Recent publications suggest that bioabsorbable vascular scaffolds (BVS) carry an excess of thrombotic complications. Our goal was to describe the results in real life and in the long term, in a series of patients who received a BVS which is currently off the market. Methods Two hundred and thirteen consecutive patients who received at least 1 BVS between May 2012 and December 2016 were analyzed. The primary objective was the incidence of the compound event “target vessel failure” that included infarction or target vessel revascularization and cardiac death. Results Seventy-five percent of patients were men with a mean age of 61.4 years. They had a high prevalence of dyslipidemia (62.44%) and smoking (65.26%). The most common cause of admission was myocardial infarction without ST elevation (53.52%). A total of 233 coronary lesions were treated, with an average of 1.3±0.3 lesions per patient. The implant was successful in 99.5% of cases. Predilatation was performed in 89.3% and post dilation in 33.5% of cases. The use of intracoronary imaging (Optical Coherence Tomography OCT and/or Intravascular ultrasonography IVUS) to optimize the BVS implant was performed in 86 patients (40.38%). With a mean follow-up of 42.5 months, the incidence of target vessel failure was 6.57% during the first 24 months and 7.98% at the end of the follow-up. Regarding the device, this included 6 cases (2.81%) of thrombosis (definitive, probable or possible) and 10 cases (4.69%) of restenosis. Patients with a history of diabetes mellitus (HR 1.72 95% CI 1.01–2.95 P=0,05) and/or chronic oral anticoagulation (HR 5.71 95% CI 1.12–28.94 P=0.04) had a higher risk of target vessel failure. The use of intracoronary imaging (OCT and/or IVUS) during the BVS implantation had a considerable trend toward significance as a protective factor (HR 0.32 95% CI 0.11–1.03 P=0.06). Conclusions In this series of patients; in real life conditions, the incidence of target vessel failure was comparable to that previously described in randomized clinical trials. The events were more frequent during the first 2 years of follow-up, in the presence of greater cardiovascular comorbidity and in the absence of intracoronary imaging during the implantation. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): European Society of Cardiology KM curve for target vessel failure (TVF)Predictor analysis for TVF

Cerebrovascular events after transcatheter mitral valve repair or guideline-directed medical therapy in patients with mitral regurgitation and heart failure in the COAPT trial

Abstract Background Our knowledge regarding the risk of cerebrovascular events (CVE) in patients with heart failure (HF) and severe secondary mitral regurgitation (SMR) treated by transcatheter mitral valve repair (TMVr) is limited. Purpose To examine the incidence, predictors, timing, and prognostic impact of CVE in patients with heart failure and SMR treated with TMVr vs guideline-directed medical therapy (GDMT) alone. Methods In the COAPT trial, 614 patients with HF with moderate-to-severe or severe SMR were randomized to TMVr with the MitraClip + GDMT vs GDMT alone. After 2 years, patients who were randomized to GDMT alone could crossover and undergo TMVr. CVE (defined as stroke or TIA) were adjudicated by an independent clinical events committee. Results A total of 43 CVE occurred in 42 patients within 3-year follow-up (34 strokes and 9 TIAs; 1 patient had both). CVE occurred in 10.0% (n=20) of patients randomized to TMVR and 11.3% (n=22) of patients randomized to GDMT alone (p=0.53) (Figure). Of the 22 CVE in the GDMT alone group, 3 occurred after the patient had crossed over to TMVr. The incidence rates in the TMVr and GDMT groups were similar within the first 3 months (incidence rate ratio [IRR] 0.78, 95% CI 0.17–3.48, p=0.74) and between 3 months and 3 years (IRR 0.83, 95% CI 0.43–1.60, p=0.58) after randomization. After multivariable adjustment, baseline estimated glomerular filtration rate (eGFR) was associated with CVE in the overall population (HR per 5 ml/min increase in eGFR 0.91, 95% CI 0.84–0.99, p=0.03). Peripheral vascular disease was associated with CVE in patients treated by GDMT (HR=3.21, 95% CI [1.35, 7.67]) but not TMVr (HR 0.53 95% CI 0.12–2.24; p-interaction=0.04). In contrast, baseline chronic oral anticoagulation use was associated with a reduced risk of CVE in patients in the TMVr group (HR 0.18, 95% CI 0.05–0.63) but not in the GDMT alone group (HR 1.66, 95% CI 0.70–3.94; p-interaction=0.004). In a time-adjusted multivariable analysis, CVE was associated with a higher risk of death (HR 2.51, 95% CI 1.54–4.08; p=0.0002), a risk that was marked in the first 30 days after the event (HR 14.21, 95% CI 7.30–27.97, p&amp;lt;0.0001), and declined thereafter (HR 1.37, 95% CI 0.72–2.59, p=0.34). Conclusions In patients with HF and severe SMR, CVE at 3 years was not infrequent, increased linearly over time, was similar after treatment with the MitraClip and GDMT alone, and was associated with a marked increase in all-cause death. Whether anticoagulation is especially effective at preventing CVE in patients treated by TMVr, as suggested by this report, warrants further study. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Abbott Figure 1

Utilization and complications of catheter ablation for ventricular arrhythmias in patients with mechanical valves

Abstract Background Catheter ablation (CA) for ventricular arrhythmias (VAs) is increasingly utilized in the recent years. Ablation for VAs in patients with mechanical valves (MVs), can be challenging due to the chronic anticoagulation therapy, limitations in accessing the cardiac chambers, the risk for entrapment of mapping or ablation catheters between the leaflets of MVs and more. Purpose To investigate the nationwide trends in utilization and complications of CA for VAs in patients with prior MVs. Methods We drew data from the US National Inpatient Sample database to identify cases of VA ablations, including premature ventricular contraction (PVC) and ventricular tachycardia (VT) ablations, in patients with MVs between 2003 and 2015. Sociodemographic and clinical data were collected, and incidence of catheter ablation complications, mortality, and length of stay were analyzed. We compared the outcomes to a propensity matched cohort of patients without prior valve surgery. Results The study population included a weighted total of 647 CA cases in patients with prior MVs. The annual number of ablations almost doubled, from 34 ablations on average during the “early years” (2003–2008) to 64 annual ablation procedures on average during the “late years” (2009–2015) of the study (p=0.001). Length of stay at the hospital did not differ significantly between patients with MVs and 649 matched patients without prior MVs (5.4±0.4, 4.7±0.3 days respectively, p=0.12). The incidence of complications was higher among patients with and without MVs (12.6% vs. 7.5% respectively, p=0.14), however, not reaching statistical significance. Moreover, the data revealed a trend toward higher mortality among patients with MVs undergoing CA compared to matched control patients without MVs (3.7% vs. 0.7% respectively, p=0.087). Conclusion The utilization of catheter ablations for ventricular arrhythmias in patients with mechanical valves increased substantially over the years. The data show a trend towards increased incidence of morality and complications in the study population, requiring further investigation in larger population cohort. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): Padeh Medical Center Research Fund

THE PARADOXICAL PRESENTATION OF PRE-ECLAMPSIA WITH DIFFUSE ALVEOLAR HEMORRHAGE AND VENOUS THROMBOSIS AS CLINICAL MANIFESTATIONS OF ANTIPHOSPHOLIPID SYNDROME

TOPIC: Pulmonary Manifestations of Systemic Disease TYPE: Medical Student/Resident Case Reports INTRODUCTION: Antiphospholipid Syndrome (APS) is an autoimmune disorder clinically defined by the presence of antiphospholipid antibodies (aPL), history of arterial or deep venous thrombosis (DVT), and/or repeat episodes of early pregnancy loss. Due to the increased risk for thrombosis, often overlooked is a rare and seemingly paradoxical association between APS and diffuse alveolar hemorrhage (DAH) - a disorder characterized by non-localized alveolar bleeding. Rare manifestation of APS presenting with preeclampsia, DAH, and DVT offers a variety of multi-disciplinary challenges. CASE PRESENTATION: A 34-year-old G6P3 woman at 28 weeks gestation with a remote history of pulmonary embolism (PE), presented to the Emergency Department with a two-day history of dyspnea and hemoptysis. Exam was remarkable for sinus tachycardia, grade 3 systolic murmur at the apex, and increased work of breathing with bilateral pulmonary rhonchi. Computed tomography (CT) scan demonstrated centrally predominant opacities without signs of PE. Bronchoscopy was significant for diffusely hemorrhagic airways with progressively hemorrhagic serial lavage aliquots. Emergent delivery was performed in the setting of Preeclampsia while high-dose steroids were administered for DAH. The patient returned to baseline over the next 3 days without returning signs of hemoptysis. Lupus anticoagulant was positive but PT and PTT were both normal. Steroids were discontinued and therapeutic enoxaparin was started for a possible novel diagnosis of APS.Six days later, she reexhibited hemoptysis. Repeat CT revealed bilateral alveolar infiltrates consistent with the recurrence of DAH. Disproportionate left lower extremity edema and a femoral vein DVT were also discovered. Anticoagulation was again withheld, high-dose steroids were re-started, and an inferior vena cava filter was placed. Repeat lupus anticoagulant testing was positive. In addition, the dilute russell viper venom time (DRVV) was prolonged in the setting of normal PT/PTT, confirming APS diagnosis. She recovered within five days and was prescribed warfarin for chronic anticoagulation, glucocorticoids were tapered, while rituximab infusions were initiated as glucocorticoid-sparing therapy. DISCUSSION: This case highlights challenges associated with the diagnosis and management of rare simultaneous manifestations of APS. In particular, the management of DAH in this scenario is unique because unlike the glucocorticoid-responsive antibodies of ANCA-associated vasculitides, aPL are not known to cause alveolar capillaritis; therefore, the role of steroids is unclear. CONCLUSIONS: Chronic anticoagulation is an absolute requirement for long-term management of APS. Yet as this case exemplifies, in the case of concomitant DAH, administration of glucocorticoids, and subsequently glucocorticoid-sparing immunosuppression is recommended as the safest approach to avoid life-threatening hemorrhage. REFERENCE #1: Cartin-Ceba R, Peikert T, Ashrani A, Keogh K, Wylam ME, Ytterberg S, Specks U. Primary antiphospholipid syndrome-associated diffuse alveolar hemorrhage. Arthritis Care Res (Hoboken). 2014 Feb;66(2):301-10. doi: 10.1002/acr.22109. PMID: 23983016. REFERENCE #2: Stoots SA, Lief L, Erkan D. Clinical Insights into Diffuse Alveolar Hemorrhage in Antiphospholipid Syndrome. Curr Rheumatol Rep. 2019 Sep 6;21(10):56. doi: 10.1007/s11926-019-0852-7. PMID: 31493005; PMCID: PMC7102334. REFERENCE #3: Janowiak P, Sieminska A, Porzezinska M, Smolenska Z, Suchanek H, Jassem E. Difficulties in the treatment of recurring diffuse alveolar hemorrhage accompanying primary antiphospholipid syndrome: a case report and literature review. Adv Respir Med. 2018;86(3). doi: 10.5603/ARM.2018.0020. PMID: 29960279. DISCLOSURES: No relevant relationships by Eric Knott, source=Web Response no disclosure on file for Eric Lang; No relevant relationships by Claudia Saborit, source=Web Response

S2312 Acute Gastrointestinal Bleeding Due to a Duodenal Hamartomatous Polyp: A Case Report

Introduction: The small bowel accounts for less than 4% of tumors involving the gastrointestinal (GI) tract. Benign small bowel lesions could be mucosal or submucosal. Polypoid mucosal lesions include Brunner’s glands hyperplasia, nodular lymphoid hyperplasia, adenomas, and hamartomas with 20% arising in the duodenum. Submucosal tumors include lipomas, leiomyomas, lymphangiomas and neurofibromas. We report a case of a large duodenal hamartomatous polyp causing significant occult GI bleeding, requiring blood transfusion and urgent endoscopic intervention. Case Description/Methods: A 65-year-old African American male with a history of colon cancer and right hemicolectomy, atrial fibrillation, end stage renal disease, and chronic anticoagulation with apixaban was admitted for generalized weakness and found to have a hemoglobin (Hgb) of 5.5 g/dL without report of overt GI bleeding. The patient was diagnosed with a large duodenal polyp three years prior with biopsy showing adenoma and Brunner’s gland hyperplasia. He had been referred to a tertiary center for endoscopic removal of the polyp, which was deferred due to his multiple major co-morbidities. After resuscitation and transfusion of two units of packed red blood cells, an esophagogastroduodenoscopy (EGD) was performed which showed the presence of the pedunculated polyp in the second portion of duodenum, measuring 2.5 cm in size with active oozing. The rest of the EGD was normal. Using a polyloop and injection of 2cc of 1:10,000 epinephrine into the peduncle, the polyp was resected using a snare and endocut. The final histological diagnosis of the polyp was hamartomatous polyp with features of Peutz-Jeghers polyp and areas of chronic inflammation. After resection of the duodenal polyp, the patient's Hgb returned to normal limits at follow up. Discussion: GI bleeding due to a duodenal polyp is very rare. As a result, there is limited data on the management of duodenal polyps regarding surveillance and resection. As demonstrated in this case, the polyp was initially not resected due to absence of symptoms and major comorbidities, but the patient later presented with significant bleeding requiring urgent endoscopic intervention. The case highlights the necessity of careful evaluation and resection of duodenal polyps > 1cm before they become symptomatic as in this case of acute GI bleeding.Figure 1.: Acute gastrointestinal bleeding due to a 2.5 cm pedunculated polyp, pathology consistent with hamartoma, within the second portion of the duodenum with active oozing of blood.

A CASE OF HEMMORRHAGIC SHOCK CAUSED BY WÜNDERLICH SYNDROME

TOPIC: Critical Care TYPE: Medical Student/Resident Case Reports INTRODUCTION: Wünderlich syndrome (WS) is a rare condition caused by acute renal hemorrhage and characterized by flank pain, flank mass and hypovolemic shock. We report a complex case of WS in an elderly gentleman with left flank pain and nausea. CASE PRESENTATION: An 81-year-old man with diabetes mellitus type 2, end-stage renal disease on hemodialysis, chronic atrial fibrillation on apixaban and coronary artery disease with history of percutaneous coronary intervention on clopidogrel who presented to a tertiary care center with acute onset left flank pain and nausea for six hours. Upon arrival, the patient was found to have a blood pressure of 78/54 mmHg and a ventricular paced rhythm at 70 bpm. His physical examination was significant for tenderness to palpation over the left flank, as well as a palpable flank mass. His hemoglobin at presentation was 12.1 gm/dL but a repeat value resulted 6.6 gm/dL. Computed tomography (CT) of the abdomen and pelvis revealed multiple renal cysts and a 25 x 11 cm hemorrhagic left kidney concerning for a ruptured cyst with extravasation of blood extending to the retroperitoneum along the psoas muscle. The patient was emergently transfused packed red blood cells, four-factor prothrombin complex concentrate and fresh frozen plasma to reverse the effect of his chronic anticoagulation and antiplatelet therapy. A multidisciplinary decision was reached that an urgent nephrectomy would be associated with a prohibitively high perioperative risk, as releasing the hematoma into the retroperitoneum may result in a complex, uncontrollable hemorrhage. The patient subsequently underwent a renal arteriogram and interventional radiology-guided selective embolization of left inferior pole artery. Repeat CT with contrast showed a stable left renal, perinephric and retroperitoneal hematoma. The patient recovered from hypovolemic shock and was successfully weaned off vasopressor support. DISCUSSION: Wünderlich syndrome is a potentially life-threatening condition that requires prompt recognition and management. The most common etiologies are malignant neoplasms (61%) followed by angiomyolipomas (29.1%). Hemorrhagic ruptured cysts are a rare cause of WS, and rupture into the perinephric space is among the rarest presentations. Emergent angioembolization may be effective. Follow-up often includes exploratory laparotomy or laparoscopy. However, if malignancy is not clearly identified on CT imaging, conservative management with repeat imaging is a reasonable alternative. CONCLUSIONS: Although rare, Wünderlich syndrome is a rapidly progressing condition with high mortality that requires time-sensitive diagnosis and emergent management. REFERENCE #1: 1. G Albi, L del Campo, D Tagarro, Wünderlich's Syndrome: Causes, Diagnosis and Radiological Management, Clinical Radiology, Volume 57, Issue 9, 2002, Pages 840-845, ISSN 0009-9260, https://doi.org/10.1053/crad.2002.0981 REFERENCE #2: Zhang JQ, Fielding JR, Zou KH. Etiology of spontaneous perirenal hemorrhage: a meta-analysis. J Urol. 2002;167(4):1593-1596. doi:10.1097/00005392-200204000-00006 REFERENCE #3: Medda M, Picozzi SC, Bozzini G, Carmignani L. Wunderlich's syndrome and hemorrhagic shock. J Emerg Trauma Shock. 2009;2(3):203-205. doi:10.4103/0974-2700.55346 DISCLOSURES: No relevant relationships by Ana de Diego Diaz, source=Web Response No relevant relationships by Jeany Villamizar, source=Web Response No relevant relationships by Ann Vu, source=Web Response

S641 Systematic Review and Meta-Analysis on Gastrointestinal Bleeding in COVID-19: A Lesson From the First 10 Months of the Pandemic

Introduction: Gastrointestinal bleeding (GIB) has been reported in patients infected with Coronavirus disease 2019 (COVID-19). Furthermore, current treatment for COVID-19 infection includes the frequent use of steroids and anticoagulants, both of which predisposes to GIB; hence the risk of GIB in this population should not be overlooked. No literature has reported the actual risk of GIB in COVID-19 patients to date. This meta-analysis investigated whether COVID-19 infection is associated with a higher risk of GIB. Methods: A systematic search of literature databases (Pubmed, Embase, Medline, Scopus, Web of Science, and Cochrane) was conducted from inception to September 2020. Observational studies or clinical trials that reported the occurrence of GIB in COVID-19 patients of age ≥18 years were included. The study protocol was registered in PROSPERO (CRD42020216564).The meta-analyses were performed with random-effect model using STATA software version 15. Meta-regression was used to identify potential moderators. Funnel plot and Egger’s intercept were used to detect potential publication bias. Results: Twelve studies with a total of 9135 participants were included (Table 1). Meta-analysis of proportion estimated the crude occurrence of overall, upper and lower GIB as 3.45 (95% CI 1.83-5.49) %, 2.47 (95% CI 0.60-5.36) % and 1.41 (95% CI 0.84-2.12) % respectively (Figure 1). Meta-regression between the occurrence of GIB and multiple clinical characteristics of the study population found cancer as a potential moderator. Age, gender, comorbidities such as hypertension, diabetes, chronic kidney disease, anticoagulants and steroids use, the mortality of the population were not found to be associated with GIB in COVID-19 patients. Conclusion: The occurrence of overall, upper and lower GIB in hospitalized COVID-19 patients is higher than that of the general population (reported incidence of 0.15%, 0.047%, and 0.033% respectively in the latter group). Our results show that pre-existing cancer increases the risk of GIB in COVID-19 patients. It is postulated that COVID-19 may exacerbate the inflammatory burden of cancer patients, resulting in mucosal breakdown and higher occurrence of GIB. There was no significant association demonstrated between GIB and the use of anticoagulants or steroids in this study.In conclusion, attention should be raised to the elevated risk of GIB in COVID-19 patients, particularly in those with pre-existing cancer.Figure 1.: Meta-analysis of occurrence of GIB in COVID-19 population.Table 1.: Study characteristics of the included studies Abbreviation: No. = number of GIB = gastrointestinal bleeding UGIB = upper gastrointestinal bleeding LGIB = lower gastrointestinal bleeding RT-PCR = reverse transcriptase-polymerase chain reaction ICU = intensive care unit WHO = World Health Organization +ve = positive.

S230 More Colonoscopies, but at What Cost? Determinants of Healthcare Utilization for Patients Requiring Inpatient Colonoscopy

Introduction: Colonoscopy has become one of the most widely utilized diagnostic and therapeutic procedures in America, with approximately 19 million performed annually. As the number of inpatient colonoscopies is on the rise, there is poor understanding of the effects on healthcare utilization. The aim of this study was to determine individual and hospital-related factors which play a role in total length of stay (LOS) and overall cost of inpatient colonoscopy. Methods: Data from the nationwide inpatient sample from 2016 to 2017 were used, which included 108,245 cases. The tenth version of the International Classification of Disease coding system (ICD10) was used for patient selection. We included demographic characteristics with a primary focus on independent variables affecting LOS and overall cost for patients requiring inpatient colonoscopy. The panel data was analyzed using hospital fixed-effects regression models to account for unobserved, time-invariant hospital characteristics. Results: The majority of the hospitals conducting inpatient colonoscopies in our sample period were large, urban, not-for-profit teaching hospitals. The average age of patients was 65 years with a largely female (52%), White (66%), low median household income (31%) and Medicare insured (60%) predominance. Female patients were found to have a shorter LOS compared to males (β = -0.3618, P < 0.05) as well as lower total cost (β = -4339.00, P < 0.05). Total hospital charges decreased with increasing patient age (β = -202.38, P < 0.05). Patients of Black (β = 0.2540, P < 0.05) and Native American races (β = 1.0265, P < 0.05) had longer LOS compared to those who are White. Among the included indications for colonoscopy, patients with inflammatory bowel disease, radiologic evidence of colitis, hematochezia and melena, and irritable bowel syndrome had both shorter LOS and lower overall cost. Patients with documented history of cerebrovascular accident had longer LOS after inpatient colonoscopy. Finally, comorbid conditions associated with higher total charges included chronic anticoagulation use, type 2 diabetes mellitus, obesity, and hypertension. Conclusion: The burden to healthcare utilization for patients undergoing inpatient colonoscopy remains largely variable amongst multiple patient etiologies. With the expanding need for inpatient colonoscopies, further studies are needed to evaluate the timing of colonoscopy with regards to patient characteristics and its impact on length of stay and overall hospitalization cost.Table 1.: Demographic characteristics and inpatient outcomes in oncologic patients with and without CDI in 2015-2017 in the US