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Abstract Background Recurrent VTE is frequent and may be fatal; the 2-week case fatality rate after recurrent pulmonary embolism is 11%. However, predictors of VTE recurrence remain uncertain. Objective To identify independent predictors of VTE recurrence, including interim exposures, adjusted for baseline characteristics and treatments. Methods Using the resources of the Rochester Epidemiology Project, we identified all Olmsted County, MN residents with objectively-diagnosed incident VTE over the 13-year period, 1988-2000. All patients surviving ≥1 day were followed forward in time for first objectively-diagnosed VTE recurrence, death or other loss to follow-up, or 12/31/2005, whichever came first. VTE recurrence was defined as new thrombosis of a previously uninvolved venous territory or re-thrombosis of a previously involved venous territory after interim clearing of the incident thrombosis. We estimated the cumulative incidence of VTE recurrence using the Kaplan Meier product limit method, both overall and by incident cancer-associated, idiopathic and non-cancer secondary VTE. For all patients with VTE recurrence, and a random sample of all patients with incident VTE, we reviewed the complete medical records in the community and collected demographic and baseline characteristics, treatments (heparin and warfarin [including proportion of time in therapeutic range], IVC filter, aspirin, statins) and interim VTE risk factor exposures. Using a case-cohort study design with Barlow’s weighting scheme, we tested these demographic, baseline and interim characteristics as potential predictors of VTE recurrence using time-dependent Cox proportional hazards modeling. Results Among 1261 incident VTE patients who survived ≥1 day, 306 developed recurrent VTE over 6,485 person-years of follow-up. The cumulative incidence of VTE recurrence at 30 and 180 days, and 1 and 5 years, were 4.5%, 8.2%, 10.5% and 20.3%, respectively. The five-year cumulative recurrence rates among patients with incident cancer-associated, idiopathic and non-cancer secondary VTE were 42.6%, 26.8% and 18.5%, respectively. Among the random cohort of 415 incident VTE cases, 381 (92%) and 359 (87%) received heparin and warfarin therapy for a median (IQR) 5 (4 - 7) and 119 (63 - 194) days, respectively. From multivariable analysis, interim exposure to trauma, major surgery (general, cardiac or gynecologic), infection, hospitalization for acute medical illness or active cancer after the incident VTE were each associated with an increased hazard of VTE recurrence, while use of warfarin and achievement of a therapeutic APTT within the first day of starting heparin were associated with reduced hazards. Although measures of time in therapeutic range while on heparin or warfarin were associated with a reduced risk of recurrence from univariate analyses, these results were not significant when adjusting for other risk factors. Conclusions Among patients with incident VTE, new exposure to trauma, major surgery, infection, hospitalization for acute medical illness or active cancer are independent predictors of VTE recurrence; patients with such exposures should be considered for VTE prophylaxis. Disclosures: No relevant conflicts of interest to declare.

Abstract Background: Venous stasis syndrome (VSS) is a relatively common long-term sequelae of deep vein thrombosis (DVT), although it frequently is noted in individuals with no prior history of DVT. Objective: To evaluate whether: (1) venous stasis syndrome (VSS) is associated with a prior history of DVT; (2a) venous outflow obstruction (VOO) and/or (2b) venous valvular incompetence (VVI) are associated with DVT; and (3) VSS is associated with VVI and/or VOO. Design: Case-control study nested within a population-based inception cohort study. Population: 230 residents of Olmstead County, MN (OCM) with a first lifetime VTE over the 25-year period, 1966 – 1990 (cases), and 135 age, gender and year of incident VTE-matched OCM residents without prior history of VTE (controls). Measurements: Physical examination and patient questionnaire for symptoms or signs of VSS, and strain gauge outflow plethysmography, continuous wave venous Doppler ultrasound, and passive venous drainage and refill testing for VOO and VVI performed between 1996 – 1998. Results: Of the 365 study participants, 43 (12%) had VOO, 136 (37%) had VVI, and 265 (73%) had VSS. In multivariate logistic regression analyses: (1) age at the follow-up visit [OR Δper 10 years: 1.70 (1.41, 2.04)], prior DVT in the affected limb [OR: 4.03 (2.32, 7.01)], and presence of prior varicose veins [OR: 4.36 (1.84, 10.31)] were significantly associated with VSS; (2a) age at the follow-up visit [OR Δper 10 years (95% CI): 1.84 (1.39, 2.44)] and prior DVT in the affected limb [OR: 5.01 (2.61, 9.63)] were significantly associated with VOO; (2b) prior DVT in the affected limb (OR: 3.91 (2.56, 5.97)], presence of prior varicose veins [OR: 2.19 (1.32, 3.63)] and symptoms of VSS prior to incident DVT [OR: 3.42 (1.46, 8.00)] significantly increased the odds for VVI; and (3) VOO (p=0.004) and VVI (p<0.0001) were highly associated with VSS. Having a DVT in the left leg was associated with a greater odds of developing VOO, VVI or VSS in that leg when compared to their association with right leg DVT (OR: 6.69 vs. 3.65; 4.82 vs. 3.09; 4.71 vs. 3.97, respectively). Interestingly, prior DVT in the opposite leg was associated with an increased odds of subsequent VVI [OR: 2.00 (1.28, 3.10) and VSS [OR: 2.20 (1.31, 3.70)], but not VOO, in the test leg. Conclusions: Prior DVT imparts an increased risk for subsequent VSS, likely due to VOO and/or VVI. The odds of VOO or VSS increases with age. Presence of varicose veins increases the odds for VVI and VSS. We speculate that the increased odds of left sided VOO, VVI and VSS in patients with prior DVT may be secondary to May-Thurner syndrome. The increased odds of VVI and VSS in the limb opposite to the one affected by prior DVT could reflect occult DVT in the test limb, inferior vena cava thrombosis, or other mechanisms leading for VVI and VSS.

BackgroundSurgical exclusion of the left atrial appendage (LAA) can be performed at the time of cardiac operation as a potential modality to decrease cardioembolic risk attributable to atrial fibrillation (AF), but it remains unclear if this decreases stroke incidence. Furthermore, it is not known whether LAA exclusion impacts the decision to discontinue anticoagulation impacting subsequent stroke risk.HypothesisLAA exclusion does not significantly alter subsequent anticoagulation use or stroke incidence.MethodsWe studied 124 patients from Olmsted County with prior history of AF who underwent cardiac surgery at our institution between 1993 and 2015. Patients were divided into two groups on the basis of LAA exclusion and matched (1:1) according to 16 pretreatment variables using propensity scores obtained from a logistic regression model. Outcome data collected through chart review for survival, stroke, and the presence and duration of anticoagulation were compared between groups.ResultsThe proportion of patients receiving anticoagulation at discharge and at 5 years was not significantly different between patients who underwent LAA exclusion and those who did not; 90% vs 81%, P = 0.156, 48% vs 49%, P = 0.722, respectively. On Kaplan‐Meier analysis there were no significant differences in time free from stroke between cases and controls. Patients discharged on oral anticoagulation (OAC) had significantly lower risk of stroke (HR = 0.19, 95% confidence interval [CI] = 0.06‐0.59, P = 0.004), independent of whether LAA closure was used.ConclusionLAA exclusion did not appear to reduce early or late stroke. Only OAC was associated with a reduction in stroke risk, underscoring the need for continued anticoagulation in high‐risk patients.

AbstractObjective:Little is known regarding the progression of preclinical atherosclerosis upon cessation of menopausal hormone therapy (MHT). This study evaluated changes in carotid artery intima-media thickness (CIMT) in a subgroup of participants during 4 years and 3 years after the Kronos Early Estrogen Prevention Study (KEEPS).Methods:Of the women enrolled in KEEPS at Mayo Clinic (n = 118), a subset (n = 76) agreed to participate in this follow-up study. KEEPS MHT assignments were placebo (PBO),n = 33; transdermal 17β-estradiol (tE2),n = 23; and oral conjugated equine estrogens group (oCEE),n = 20. CIMT was measured by B-mode ultrasonography. Longitudinal analysis of CIMT was performed using all available data from pre-, on-, and post-treatment periods.Results:At 7 years, median age of participants was 60.2 years; median time since menopause was 8.5 years. The mean difference in rates of increase was significantly greater over the post- than on-treatment period within the oCEE group (0.010 [0.002-0.017] mm/y), but not within the PBO (0.006 [−0.001 to 0.012] mm/y;P = 0.072)or tE2(0.002 [−0.005 to 0.010] mm/y;P = 0.312) groups. There were, however, no significant treatment differences in the linear trends over those intervals (P = 0.524).Conclusions:Cessation of MHT at the lower doses and formulations used in KEEPS did not appear to alter the trajectory of CIMT over a 3-year follow-up period. CIMT, however, increased in all groups over the entire 7-year timeframe as expected with age and timing of menopause possibly key contributors.

BACKGROUND: Selective serotonin reuptake inhibitor (SSRI) and serotonin–norepinephrine reuptake inhibitor (SNRI) use is known to alter platelet activation and aggregation leading to impairment in hemostasis. Previous studies are ambiguous with regard to bleeding, transfusion, and perioperative complications in patients undergoing cardiac surgery. The purpose of this study was to evaluate the risk of perioperative bleeding, transfusion, morbidity, and mortality in cardiac surgical patients taking SSRI/SNRIs compared with propensity-matched controls. METHODS: Adult patients undergoing cardiac surgery with cardiopulmonary bypass at our institution between January 1, 2004, and December 31, 2014, were eligible for study inclusion. Patients taking SSRI/SNRI medications at the time of surgery were identified and compared against all other patients not taking SSRI/SNRI medications to produce well-matched groups via propensity score analysis. Patients taking SSRI/SNRI medications were matched in a 1:1 ratio to control patients not taking these medications based on an internally estimated propensity score. Primary outcomes included perioperative blood transfusion, chest tube output, and reoperation for bleeding. Secondary outcomes included postoperative complications (renal failure, stroke or transient ischemic accident, prolonged mechanical ventilation, and perioperative myocardial infarction), intensive care unit (ICU) and hospital length of stay (LOS), and 30-day mortality. RESULTS: A total of 1417 pairs of SSRI/SNRI patients and matched controls were retained for analysis. Between SSRI/SNRI patients and matched controls, there was no significant difference in postoperative chest tube output (median, 750.0 vs 750.0 mL; P = .860) or reoperation for bleeding (2.8% vs 2.5%; P = .892). Perioperative transfusion rates across all time points and blood product type were not significantly different between groups, with the overall perioperative transfusion rate for SSRI/SNRI patients 66.5% vs 64.9% for matched controls ( P = .697). Patients in the SSRI/SNRI group had a higher rate of prolonged mechanical ventilation (13.1% vs 8.6%; P = .002), longer ICU LOS (median, 25.5 vs 23.8 hours; P < .001), and longer hospital LOS (median, 6.0 vs 5.0 days; P < .001). Remaining mortality and outcome data were similar between groups. CONCLUSIONS: SSRI/SNRI use was not associated with an increased risk of bleeding or transfusion in patients undergoing cardiac surgery. While there was prolonged mechanical ventilation and increased ICU/hospital LOS in the SSRI/SNRI group, it is unclear that this finding is the result of such medications or rather associated with the underlying psychiatric condition for which they are prescribed. The results of this study suggest that perioperative interruption of SSRI/SNRIs to reduce the risk of perioperative bleeding and transfusion is unwarranted and may risk destabilization of patients’ psychiatric condition.