Extended Anticoagulation for Venous Thromboembolism: A Survey of the American Venous Forum and the European Venous Forum
Shaydakov, Maxim E; Ting, Windsor; Sadek, Mikel; Aziz, Faisal; Diaz, Jose A; Comerota, Anthony J; Lurie, Fedor; Blebea, John; Eklöf, Bo G; Lugli, Marzia; De Maeseneer, Marianne G R; Kakkos, Stavros K; Nicolaides, Andrew; Heim, Dominik; Welch, Harold J
OBJECTIVE:Extended anticoagulation should always be considered after standard treatment for an unprovoked episode of venous thromboembolism (VTE). It may also be considered in selected patients with provoked VTE. However, evidence-based protocols suggested by some clinical guidelines and risk assessment tools to guide this practice are limited and ambiguous. The goal of this survey research was to analyze current practices in applying extended anticoagulation therapy in patients with VTE among members of the American Venous Forum (AVF) and the European Venous Forum (EVF). METHODS:An online survey was created by the AVF Research Committee. The survey consisted of sixteen questions to identify the country of practice, specialty, experience of participating physicians, and their clinical practice patterns in applying extended anticoagulation in VTE patients. The survey was distributed over email to the members of the AVF and EVF. RESULTS:A total of 144 practitioners, 48 (33%) AVF members and 96 (66%) EVF members, participated in the survey. The majority of respondents identified themselves as vascular specialists with primary certification in vascular surgery (70%), vascular medicine/angiology (9%), and venous disease/phlebology (3%). Seventy-two percent of participants believe that the risk of VTE recurrence generally overweighs the risk of bleeding in patients with unprovoked VTE. Extended anticoagulation may be utilized by 97% of providers. Different patterns in real world clinical practice were identified. More than half of practitioners estimated VTE recurrence and bleeding risk subjectively. The antithrombotic drugs most commonly used for secondary prophylaxis were rivaroxaban, apixaban, warfarin, dabigatran, and aspirin, in decreasing order of frequency. Among the reasons selected for not considering extended anticoagulation on a regular basis were the lack of specific clinical practice guidelines (24%), the lack of published evidence (9%), and the absence of valid VTE/bleeding risk prediction calculators (8%). Twelve participants (8%) stated that extended anticoagulation was not beneficial for the majority of patients with VTE. Ten participants (7%) indicated that prescribing extended anticoagulation was outside the scope of their specialty. CONCLUSIONS:There are different practice patterns in extending anticoagulation beyond the standard treatment in patients with VTE. Major gaps in knowledge remain a serious challenge at least partially explaining inaccuracy and inconsistency in long-term VTE management. Appropriately designed studies are needed to evaluate risk stratification tools when contemporary best medical therapy is used, accurately predict VTE recurrence and its long-term outcomes, and to tailor safe and effective secondary prophylaxis.
Patients With Carotid Occlusion Require Close Surveillance and Have a High Rate of Subsequent Carotid Intervention [Meeting Abstract]
Speranza, G; Harish, K; Rockman, C; Gordon, R; Sadek, M; Jacobowitz, G; Chang, H; Garg, K; Maldonado, T S
Objective: There is a paucity of literature on the natural history of extracranial carotid artery occlusion (CAO). This study reviews the natural history of this patient cohort.
Method(s): This single-institution retrospective analysis studied patients with CAO diagnosed by duplex ultrasound test between 2010 and 2021. Patients were identified by searching our office-based accredited vascular laboratory database. Imaging and clinical data were obtained via our institutional electronic medical record.
Result(s): A total of 5523 patients underwent carotid artery duplex examination during the study period. The CAO cohort consisted of 140 patients, as characterized in Table I; incidence of CAO was 2.5%. A total of 61.3% (n = 86) of patients were asymptomatic at diagnosis. A total of 27.9% (n = 39) were diagnosed after a stroke or transient ischemic attack, with 16.4% ipsilaterally affected, 7.9% contralaterally affected, and 3.6% with unclear laterality. For 23 patients with prior duplex imaging demonstrating ipsilateral patency, 26.1% had <50% ipsilateral stenosis, 39.1% had 50%-69% stenosis, and 26.1% had >70% stenosis at a mean of 32.8 +/- 26.4 months before CAO diagnosis. At CAO diagnosis, 55.2% of patients had <50% contralateral stenosis, 24.8% had 50%-69% stenosis, and 9.9% had >70% stenosis. Ninety-five patients (67.9%) had duplex imaging follow-up (mean: 42.7 +/- 31.3 months). Six patients (6.3%) developed recanalization with the mean occurrence of 42.9 +/- 32.6 months after diagnosis. Four patients (2.9%) developed subsequent stroke ipsilateral to the CAO with the mean occurrence of 27.8 +/- 39.0 months after diagnosis. Thirteen patients (9.3%) developed other related symptoms, including global hypoperfusion (5.0%), cognitive changes (2.9%), and transient ischemic attack (1.4%). Ten patients (7.1%) underwent eventual ipsilateral intervention, including carotid endarterectomy (n = 6), transfemoral carotid artery stenosis (n = 2), transcarotid artery revascularization (n = 1), and carotid bypass (n = 1), with the mean occurrence of 17.7 +/- 23.7 months after diagnosis. Before intervention, seven occlusions on duplex imaging were recharacterized as severe stenosis per periprocedural CT or MR imaging. Two CAOs were intervened on subsequent to recanalization. One patient with confirmed CAO underwent bypass for symptoms of global cerebral hypoperfusion. Intervention characteristics are shown in Table II. The aggregate rate of developing recanalization, related stroke or symptoms, or undergoing ipsilateral intervention was 19.3%. A total of 16 patients (11.4%) underwent contralateral intervention, including carotid endarterectomy (8.6%), transcarotid artery revascularization (2.1%), and transfemoral carotid artery stenosis (0.7%), with the mean occurrence of 11.5 +/- 18.2 months after diagnosis.
Conclusion(s): In this large, institutional cohort of patients with CAO diagnosed by duplex ultrasound test, a clinically meaningful subset of patients experienced recanalization, stroke, or related symptoms. Most patients with CAO per duplex ultrasound test who underwent intervention were subsequently recharacterized as having severe stenosis. These data suggest that patients with CAO may benefit from aggressive medical management, close follow-up, and confirmatory imaging. [Formula presented] [Formula presented]
Response to clopidogrel in patients undergoing lower extremity revascularization
Tawil, Michael; Maldonado, Thomas S; Xia, Yuhe; Berland, Todd; Cayne, Neal; Jacobowitz, Glenn; Lugo, Joanelle; Lamparello, Patrick; Sadek, Mikel; Rockman, Caron; Berger, Jeffrey S
OBJECTIVES/OBJECTIVE:Clopidogrel is effective at decreasing cardiovascular events in patients with peripheral artery disease (PAD); however, its effect on limb outcomes are less known. This study investigated the variability in response to clopidogrel and its relationship with clinical limb outcomes. METHODS: RESULTS: CONCLUSIONS:Among patients undergoing lower extremity revascularization on clopidogrel, higher baseline percent aggregation is associated with increased risk for major adverse limb events.
Initial US experience with the BlueLeaf Endovenous Valve Formation System [Meeting Abstract]
Marston, W; Muluk, S; Sadek, M; Gagne, P; Dexter, D
Objective: Chronic venous insufficiency (CVI), owing to deep vein reflux (DVR) and venous obstruction, is widespread and associated with significant morbidity. The BlueLeaf System has been designed to treat patients with symptomatic CVI with evidence of DVR. The BlueLeaf device is intended to form autogenous tissue leaflets from vein walls without the use of a permanent vascular implant. This report describes the early outcomes of the initial 6 patients treated in the United States.
Method(s): In 2 US centers, patients with DVR and CEAP classification of C5 or C6 were screened and treated using the BlueLeaf System. Retrograde percutaneous access was obtained through the common femoral vein, and contrast venography and intravascular ultrasound examination were used to identify at least two valve formation sites in the popliteal or femoral veins. The 16F study device was introduced and used to form up to two monocuspid valves. Post procedurally, patients were prescribed enoxaparin injections for 30 days, followed by 6 months of oral anticoagulation. Follow-up evaluations included duplex ultrasound examination, Venous Clinical Severity Score, and patient reported outcome surveys. Perioperative and postoperative adverse events were captured including the incidence of DVT, pulmonary embolism, and access site complications.
Result(s): Six patients were identified meeting the inclusion criteria with a mean age of 57.2 +/- 12.1 years, and a mean body mass index of 34.4 +/- 3.6. CEAP clinical class was C5 in two and C6 in four patients and four patients had a documented history of DVT. One or more monocuspid valves were successfully formed in 5/6 (83%) patients. In 1 patient with severe post-thrombotic changes the valve formation attempt was unsuccessful. Median follow-up time was 12 weeks. At 12 weeks, there was a mean decrease in reflux time (seconds) in the mid popliteal vein of -0.3 (-1.0 to 1.9) and a mean decrease in the peak reflux velocity (cm/sec) (PRV) of -3.0 (-1 to -50). Four of the five (80%) of patients that had reached the 12-week visit, experienced a decrease in Venous Clinical Severity Score with a mean improvement of -3.6 points. To date, there have been no DVT nor pulmonary embolism reported. One patient experienced intraprocedural ST segment depression. No access site related complications were reported. Nonocclusive valve cusp thrombus was reported in 1 patient, which resolved by 30 days.
Conclusion(s): In this initial US experience, endovenous valve formation was successful in the majority of cases. The limited data suggests meaningful improvement in symptoms with only a modest improvement in hemodynamic measures. The INFINITE-US study is ongoing and the enrollment of additional patients will help refine the BlueLeaf procedure as well as inform on the best hemodynamic measures.
The Presence of a Pathologic Perforator May be Predictive of Central Venous Pathology and Multilevel Disease in Severe Chronic Venous Insufficiency
Li, Chong; Nwachukwu, Chukwuma; Jacobowitz, Glenn R; Kabnick, Lowell S; Maldonado, Thomas S; Rockman, Caron B; Berland, Todd L; Sadek, Mikel
INTRODUCTION/BACKGROUND:The treatment of a refluxing perforator is indicated in the setting of severe chronic venous insufficiency, but there are limited data on the presence of multilevel disease in these patients. This study sought to evaluate whether the presence of a pathologic perforator is predictive of the presence of central venous pathology. METHODS:This study was a retrospective review of the institutional vascular quality initiative (VQI) database. Consecutive patient-limbs were identified who underwent intervention of refluxing perforators. The patients who underwent imaging, including MRI or CT (Group A) were compared to those who did not undergo imaging (Group B). The treated limbs in Group A were also compared to the contralateral limbs as an internal control. Anatomical findings on imaging were analyzed by two independent investigators. The primary outcome was the presence and degree of central venous stenosis as measured by an orthogonal diameter reduction of > 50% by axial imaging. Secondary outcomes included demographic and clinical differences between the two groups, frequency of central venous intervention, and duration of ulcer healing. Standard statistical analysis was performed. RESULTS:Ninety-three patient-limbs underwent treatment of a pathologic perforator, with 30 in Group A and 63 in Group B. The following demographic and clinical variables were higher in Group A compared to Group B: Male gender, BMI, deep venous thrombosis history, recent or active anticoagulation use, perforator diameter, Clinical Etiology Anatomy Pathophysiology class 4, 5 or 6, and Venous Clinical Severity Score. Radiographic analysis of Group A revealed concordance of a treated pathological perforator with an ipsilateral central venous stenosis in 53.3% of patients, and a higher frequency of common iliac vein stenosis (50% vs 21.4%, P = 0.024) and external iliac vein stenosis (20% vs 0%, P = 0.012) compared to the contralateral limbs. When separated by left or right limb, the left limbs exhibited a greater degree of common iliac vein stenosis as compared to the contralateral limbs (50.7Â±20.9% vs 16.3Â±16.5%, P < 0.001) as well as a greater frequency of >50% common iliac vein stenosis (46.7% vs 13.3%, P = 0.046). The right limbs exhibited a greater frequency of > 50% external iliac vein stenosis as compared to contralateral limbs (33.3% vs 0%, P = 0.022). CONCLUSIONS:This study suggests that patients with severe chronic venous insufficiency who undergo treatment for a pathologic perforator may have additional ipsilateral central venous pathology, supporting the presence of multilevel disease. Additional axial imaging might unmask central venous pathology and provide another option for treatment.
Common iliac vein stenting for May-Thurner syndrome and subsequent pregnancy
Speranza, Giancarlo; Sadek, Mikel; Jacobowitz, Glenn
BACKGROUND:For women with left common iliac vein compression (ie, May-Thurner syndrome) who undergo venous stenting and subsequently become pregnant, concerns have been raised regarding a possible compromise of stent patency due to compression from the gravid uterus and the hypercoagulability induced by pregnancy. Only a small body of literature exists on this subject, and limited management guidelines are available. The present study was designed to evaluate the safety of iliac vein stenting for May-Thurner syndrome (MTS) with subsequent pregnancy. METHODS:Female patients who had undergone common iliac vein stenting at our center who were aged 18 to 45Â years and had subsequently become pregnant were identified. A retrospective medical record review of eight eligible patients was conducted, recording the demographics, procedural characteristics, and anticoagulation strategies. The primary outcome evaluated was stent patency. RESULTS:All eight patients had undergone left common iliac vein stenting for MTS. A total of eight stents were placed, and all demonstrated duplex ultrasound patency throughout pregnancy and postpartum. Seven patients delivered healthy pregnancies, and one experienced a stillbirth. The clinical CEAP (clinical, etiologic, anatomic, pathophysiologic) class remained unchanged or improved from pregnancy to postpartum for all patients. The average age at stent placement was 31Â Â± 5Â years, and the average interval from stent placement to pregnancy was 28Â Â± 19Â months. One patient developed nonobstructive deep vein thrombosis (DVT) of the left femoral vein during pregnancy and was treated with therapeutic enoxaparin. The nonobstructive DVT did not compromise the iliac vein stent. Two patients received low-dose aspirin and prophylactic doses of enoxaparin, one for a history of DVT and factor V Leiden and one for a recent history of fertility treatment. The five remaining patients received no anticoagulation, three received low-dose aspirin, and two received no antiplatelet therapy. CONCLUSIONS:Common iliac vein stent patency was not compromised by subsequent pregnancy in our eight patients with MTS. Furthermore, the stents remained patent throughout pregnancy in patients receiving a wide range of anticoagulation and antiplatelet treatments, suggesting that no uniform therapeutic threshold exists and treatment should be individualized. For most patients, low-dose aspirin alone or no treatment was adequate. This could have implications for counseling women who require intervention for MTS and are of child-bearing age.
Natural History of Incidentally Noted Celiac Artery Aneurysms [Meeting Abstract]
Hartwell, C A; Johnson, W; Nwachukwu, C; Garg, K; Sadek, M; Maldonado, T S; Jacobowitz, G R; Kim, D; Rockman, C
Objective: Celiac artery aneurysms (CAAs) are unusual. The reported literature is skewed toward those treated by operative or endovascular intervention. The goal of the present study was to investigate the natural history of untreated CAAs.
Method(s): We performed a single-institution retrospective analysis of patients with CAAs diagnosed by computed tomography from 2015 to 2019. The patients were identified by searching our institutional radiology database. The radiologic, demographic, and follow-up clinical and imaging data were obtained from the electronic medical records.
Result(s): The analyzed cohort consisted of 76 patients (86.8% were men). The mean age was 69.8 years (range, 29-93 years). The medical comorbidities included hypertension (64.5%), diabetes (9.2%), coronary disease (18.4%), and hypercholesterolemia (46.1%). Concomitant vascular disease was noted and included AAA in 13.2%, an additional visceral aneurysm in 10.5%, and a visceral artery anomaly in 11.8%. The mean CAA diameter at the index study was 15.4 mm (range, 7-30 mm). Most (97.3%) were believed to be true aneurysms. Additional characteristics included thrombus (9.2%), calcification (26.3%), and dissection (11.8%). Of the 76 patients, 45 (59.2%) had had follow-up imaging data available for analysis. The mean clinical follow-up time was 31.2 months. The follow-up time for only those with subsequent imaging studies available was 25.2 months. During this period, 16 CAAs (21.1%) had enlarged in size and 29 (79.9%) had remained stable. No patient had developed symptoms or rupture. One patient (1.3%) had undergone intervention for an increasing size in the setting of chronic dissection. On univariate analysis, the only factor that was significantly associated with an increased risk of growth was younger age (mean age at diagnosis, 63.4 years vs 74.3 years; P =.005). We could not identify any other factor that was significantly predictive of, or protective against, aneurysm growth. For patients with follow-up imaging studies available, the freedom from aneurysm growth or intervention was 63% at 37 months. For the entire cohort, the freedom from aneurysm rupture or the need for intervention was 90% at 59 months.
Conclusion(s): The results from the present large study of patients with untreated CAAs revealed that very few lesions either enlarged to a clinically meaningful degree, became symptomatic, or required intervention during a 31.2-month follow-up period. Guidelines that suggest repair of CAAs >=2 cm in diameter might be overly aggressive. Close follow-up with serial imaging studies, especially for patients who are younger at diagnosis, might be preferred for most patients with an incidentally noted true CAA.
Outcomes of transfemoral carotid artery stenting and transcarotid artery revascularization for restenosis after prior ipsilateral carotid endarterectomy
Chang, Heepeel; Rockman, Caron B; Veith, Frank J; Kashyap, Vikram S; Jacobowitz, Glenn R; Sadek, Mikel; Garg, Karan; Maldonado, Thomas S
OBJECTIVE:Restenosis after carotid endarterectomy (CEA) poses unique therapeutic challenges, with no specific guidelines available on the operative approach. Traditionally, transfemoral carotid artery stenting (TfCAS) has been regarded as the preferred approach to treating restenosis after CEA. Recently, transcarotid artery revascularization with a flow-reversal neuroprotection system (TCAR) has gained popularity as an effective alternative treatment modality for de novo carotid artery stenosis. The aim of the present study was to compare the contemporary perioperative outcomes of TfCAS and TCAR in patients with prior ipsilateral CEA. METHODS:The Vascular Quality Initiative database was reviewed for patients who had undergone TfCAS and TCAR for restenosis after prior ipsilateral CEA between January 2016 and August 2020. The primary outcome was the 30-day composite outcome of stroke and death. The secondary outcomes included 30-day stroke, transient ischemic attack (TIA), myocardial infarction (MI), death, and composite 30-day outcomes of stroke, death, and TIA, stroke and TIA, and stroke, death, and MI. Multivariable logistic regression models were used to evaluate the outcomes of interest after adjustment for potential confounders and baseline differences between cohorts. RESULTS:Of 3508 patients, 1834 and 1674 had undergone TfCAS and TCAR, respectively. The TCAR cohort was older (mean age, 71.6Â years vs 70.2Â years; PÂ < .001) and less likely to be symptomatic (27% vs 46%; PÂ < .001), with a greater proportion taking aspirin (92% vs 88%; PÂ = .001), a P2Y12 inhibitor (89% vs 80%; PÂ < .001), and a statin (91% vs 87%; PÂ = .002) compared with the TfCAS cohort. Perioperatively, the TCAR cohort had had lower 30-day composite outcomes of stroke/death (1.6% vs 2.7%; PÂ = .025), stroke/death/TIA (1.8% vs 3.3%; PÂ = .004), and stroke/death/MI (2.1% vs 3.2%; PÂ = .048), primarily driven by lower rates of stroke (1.3% vs 2.3%; PÂ = .031) and TIA (0.2% vs 0.7%; PÂ = .031). Among asymptomatic patients, the incidence of stroke (0.6% vs 1.4%; PÂ = .042) and the composite of stroke/TIA (0.8% vs 1.8%; PÂ = .036) was significantly lower after TCAR than TfCAS, and TCAR was associated with a lower incidence of TIA (0% vs 1%; PÂ = .038) among symptomatic patients. On adjusted analysis, the TCAR cohort had lower odds of TIA (adjusted odds ratio, 0.17; 95% confidence interval, 0.04-0.74; PÂ = .019). CONCLUSIONS:Among patients undergoing carotid revascularization for restenosis after prior ipsilateral CEA, TCAR was associated with decreased odds of 30-day TIA compared with TfCAS. However, the two treatment approaches were similarly safe in terms of the remaining perioperative outcomes, including stroke and death and stroke, death, and MI. Our results support the safety and efficacy of TCAR in this subset of patients deemed at high risk of reintervention.
Statin Use Reduces Mortality in Patients Who Develop Major Complications After Transcarotid Artery Revascularization [Meeting Abstract]
Chang, H; Zeeshan, M; Rockman, C B; Veith, F J; Laskowski, I; Kashyap, V S; Jacobowitz, G R; Garg, K; Sadek, M; Maldonado, T S
INTRODUCTION AND OBJECTIVES: The impact of preoperative statin use in patients undergoing transcarotid artery revascularization (TCAR) is not well established. The aim of this study was to evaluate the effect of statin on postoperative outcomes after TCAR.
METHOD(S): Vascular Quality Initiative registry (2012-2020) was queried for patients undergoing TCAR. Patient demographics, perioperative characteristics and 30-day outcomes were compared between patients treated with and without statins at least 30 days preoperatively. Multivariable logistic regression models were used to estimate the effect of statins on postoperative outcomes. RESULTS: A total of 15,797 patients underwent TCAR, and 10,116 (64%) were males. 14,152 (89.6%) patients were on statin preoperatively (Table). There was higher incidence of both prior ipsilateral stroke (17.2% vs 13.5%; P<.001) and recent ipsilateral stroke (<= 30 days; 7.1% vs 5.6%; P=.02) in the statin group. Perioperative stroke and major adverse cardiac event (MACE; myocardial infarction, congestive heart failure and dysrhythmia) occurred in 1.5% and 2.4% among patients on statins and 1.4% and 2.3% among those not on statins, respectively. After adjusting for potential confounders and baseline differences, statin use was associated with 62% reduction in the odds of mortality (OR 0.38; 95% CI, 0.19-0.99; P=.047) in patients who developed a perioperative stroke or MACE after TCAR (Figure).
CONCLUSION(S): Statin use was associated with a significant reduction in postoperative mortality in patients who develop a stroke or MACE after TCAR. Therefore, strict adherence to statin is strongly recommended, particularly in patients who may be at high risk of major postoperative complications.[Formula presented]
Histological Assessment of Lower Extremity Deep Vein Thrombi from Patients Undergoing Percutaneous Mechanical Thrombectomy
Yuriditsky, Eugene; Narula, Navneet; Jacobowitz, Glenn R; Moreira, Andre L; Maldonado, Thomas S; Horowitz, James M; Sadek, Mikel; Barfield, Michael E; Rockman, Caron B; Garg, Karan
BACKGROUND:Histological analyses of deep vein thrombi (DVT) are based on autopsy samples and animal models. No prior study has reported on thrombus composition following percutaneous mechanical extraction. As elements of chronicity and organization render thrombus resistant to anticoagulation and thrombolysis, a better understanding of clot evolution may inform therapies. METHODS:We performed histologic evaluation of DVTs from consecutive patients undergoing mechanical thrombectomy for extensive iliofemoral DVTs using the Clottriever/ Flowtriever device (Inari Medical, Irvine, CA). Thrombi were scored in a semi-quantitative manner based on the degree of fibrosis (collagen deposition on trichrome stain), and organization (endothelial growth with capillaries and fibroblastic penetration). RESULTS:Twenty-three specimens were available for analysis with 20 presenting with acute DVT (â‰¤14 days from symptom onset). Eleven of 23 patients (48%) had >5% fibrosis (collagen deposition) and 14/23 patients (61%) had >5% organization (endothelial growth, capillaries, fibroblasts). Four patients with acute DVT had â‰¥25% organized thrombus and 2 had â‰¥ 25% collagen deposition. Among the 20 patients with acute DVT, 40% had >5% fibrosis and 55% had > 5% organization. Acuity of DVT did not correlate with the fibrosis or organizing scores. CONCLUSIONS:A large proportion of patients with acute DVT have histologic elements of chronicity and fibrosis. A better understanding of the relationship between such elements and response to anticoagulants and fibrinolytics may inform our approach to therapeutics.