Hodge, David O.

Background. Currently, no surveillance guidelines for hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT) exist. In this retrospective, multicenter study, we have investigated the role of surveillance imaging on postrecurrence outcomes. Methods. Patients with recurrent HCC after LT from 2002 to 2016 were reviewed from 3 transplant centers (University of California San Francisco, Mayo Clinic Florida, and University of Toronto). For this study, we proposed the term cumulative exposure to surveillance (CETS) as a way to define the cumulative sum of all the protected intervals that each surveillance test provides. In our analysis, CETS has been treated as a continuous variable in months. Results. Two hundred twenty-three patients from 3 centers had recurrent HCC post-LT. The median follow-up was 31.3 months, and median time to recurrence was 13.3 months. Increasing CETS was associated with improved postrecurrence survival (hazard ratio, 0.94; P < 0.01) as was treatment of recurrence with resection or ablation (hazard ratio, 0.31; P < 0.001). An receiver operating characteristic curve (area under the curve, 0.64) for CETS covariate showed that 252 days of coverage (or 3 surveillance scans) within the first 24 months provided the highest probability for aggressive postrecurrence treatment. Conclusions. In this review of 223 patients with post-LT HCC recurrence, we found that increasing CETS does lead to improved postrecurrence survival as well as a higher probability for aggressive recurrence treatment. We found that 252 days of monitoring (ie, 3 surveillance scans) in the first 24 months was associated with the ability to offer potentially curative treatment.

Abstract Objectives The aim of this study was to describe management of recurrent pulmonary vein stenosis (PVS) and determine if stenting is superior to balloon angioplasty (BA) in preventing subsequent restenosis. Background PVS is a serious complication of atrial fibrillation ablation. BA and stenting are effective therapies; however, restenosis frequently occurs. Here we report management of recurrent stenosis. Methods This was a prospective observational study performed from 2000 to 2014. Results One hundred and thirteen patients with severe PVS underwent intervention in 88 veins treated with BA and 81 treated with stenting. Forty‐two patients experienced restenosis. Restenosis was more common in veins treated with BA (RRR 53% [95% CI 32–70%, p = .008]). A second intervention was performed in 41 patients. In the 34 vessels treated with initial BA, 24 were treated for restenosis with a stent and 10 were treated with a second BA. The recurrence rate was 46% in those treated with BA followed by stenting and 50% in those treated with two BA procedures. In the 22 veins treated with initial stenting, 9 were treated with another stent and 13 were treated with BA. The recurrence rate was 44% in those treated with a second stent and 46% for those treated with a stent followed by BA. The risk of a third stenosis was the same among all groups (Analysis of variance [ANOVA] p = .99). Limited sample size precluded analysis of outcome by stent size. Conclusions Restenosis occurred in 44% of patients overall. Management is challenging; stenting does not appear to be superior to BA.

AbstractBackgroundThe accurate separation of undifferentiated wide complex tachycardias (WCTs) into ventricular tachycardia (VT) or supraventricular wide complex tachycardia (SWCT) using conventional, manually‐applied 12‐lead electrocardiogram (ECG) interpretation methods is difficult.PurposeWe sought to devise a new WCT differentiation method that operates solely on automated measurements routinely provided by computerized ECG interpretation software.MethodsIn a two‐part analysis, we developed and validated a logistic regression model (ie, VT Prediction Model) that utilizes routinely available computerized measurements derived from patients' paired WCT and baseline ECGs.ResultsThe derivation cohort consisted of 601 paired WCT (273 VT, 328 SWCT) and baseline ECGs from 421 patients. The VT Prediction Model, composed of WCT QRS duration (ms) (P < .0001), QRS duration change (ms) (P < .0001), QRS axis change (°) (P < .0001) and T axis change (°) (P < .0001), yielded effective VT and SWCT differentiation (area under the curve [AUC]: 0.924; confidence interval [CI]: 0.903‐0.944) for the derivation cohort. The validation cohort comprised 241 paired WCT (97 VT, 144 SWCT) and baseline ECGs from 177 patients. The VT Prediction Model's implementation on the validation cohort yielded effective WCT differentiation (AUC: 0.900; CI: 0.862‐0.939) with overall accuracy, sensitivity, and specificity of 85.0%, 80.4%, and 88.2%, respectively.ConclusionThe VT Prediction Model is an example of how readily available ECG measurements may be used to distinguish VT and SWCT effectively. Further study is needed to develop and refine newer WCT differentiation approaches that utilize computerized measurements provided by ECG interpretation software.

Background: Randomized controlled trials leading to the approval of apixaban and rivaroxaban for venous thromboembolism (VTE) did not include patients with UE-DVT. Limited observational data has been published on outcomes in this setting and no direct comparison to traditional anticoagulation has been performed. Objective: Evaluate the safety and effectiveness of rivaroxaban and apixaban for the treatment of acute UE-DVT compared to low-molecular weight (LWMH) and warfarin. Methods: Consecutive patients with VTE were enrolled into the Mayo Clinic VTE Registry, between March 1, 2013 and July 22, 2019, were followed prospectively. Clinical, demographic and imaging data were collected at the time of study recruitment. Patients with a diagnosis of acute UE-DVT who received either rivaroxaban, apixaban, LMWH or warfarin within the first 14 days after diagnosis and who completed at least 3 months of anticoagulant therapy or had an outcome event in that period were included into the analysis. Recurrent VTE, major bleeding, clinical relevant non-major bleeding (CRNMB), and death were assessed at 3 months, in person whenever feasible, or by mailing a written questionnaire or a scripted phone interview. The study was approved by Mayo Clinic Institutional Review Board. Results: One hundred and thirty-four patients with acute UE-DVT were included. Forty-one were treated with apixaban, 32 with rivaroxaban, and 61 with LWMH and/or warfarin. The mean age was 58.3 years, mean BMI was 28.2, and 59% were male (Table 1). Patients treated with LMWH / warfarin were older (61.3 vs 55.8, p=0.04) and had a lower BMI (27.1 vs 29.0, p=0.0496). Twenty-six (19%) patients had catheter-associated UE-DVT, 93 (69.4%) had a diagnosis of malignancy, and 16 (11.9%) had concurrent pulmonary embolism, which were similar between groups. More patients on apixaban /rivaroxaban were receiving chemotherapy (53.4% vs 47.5%, p=0.04) and had recent surgery (13.7% vs 3.3%, p=0.04) compared to LMWH / warfarin. At 3 months of follow up, 1 recurrent VTE occurred in patients treated with LMWH /warfarin and none of those treated with apixaban /rivaroxaban (p=0.27). Major bleeding occurred in 2 patients treated with LMWH /warfarin and in none of those treated with apixaban /rivaroxaban (p=0.12). CRNMB occurred in 1 patient treated with LWMH /warfarin and 5 patients treated with apixaban / rivaroxaban (p=0.15). Two of the CRNMBs occurred with rivaroxaban and 3 occurred with apixaban. Death occurred in 5 patients treated with LMWH /warfarin and in none of the apixaban /rivaroxaban treated patients (p=0.01). Conclusion: This single institution prospective study adds to the limited experience with apixaban and rivaroxaban for acute UE-DVT. Treatment of UE-DVT with rivaroxaban and apixaban appears to be as safe and effective as LMWH/warfarin after 3 months of anticoagulation. Disclosures McBane: BMS: Research Funding.

Background: Incidental pulmonary embolism (PE) is not infrequently found on CT scans with highest incidence reported in patients with cancer. It is unclear whether patients with symptomatic pulmonary embolism (iPE) have different clinical profile or outcomes compared to patients with symptomatic PE (sPE) and whether this is affected by the presence or type of malignancy. Objective: Compare baseline characteristics of patients diagnosed with iPE to patients with sPE with attention to cancer-specific risk factors as well as evaluate clinical outcomes. Methods: Consecutive patients enrolled in the Mayo Thrombophilia Clinic VTE Registry between March 1, 2013 and December 31st, 2018 with PE were followed prospectively. Outcomes of recurrent venous thromboembolism (VTE), major bleeding, clinically relevant non-major bleeding (CRNMB) and mortality data were collected every 3 months. Clinical outcomes were analyzed with specific focus on patients with cancer. Information was collected and managed using REDCap (Research Electronic Data Capture) and data analysis was performed using SAS software (SAS Institute Inc., Cary, North Carolina). Results: Out of a total of 1033 patients with PE in VTE registry, there were 655 patients with PE (284 with incidental and 363 symptomatic) who completed at least 3 months of anticoagulation and were started on treatment within 14 days of diagnosis. Apixaban was used in 220 (34 %), Rivaroxaban 175 (27 %), Enoxaparin 179 (27%), and Warfarin in 81 (12 %) patients. Overall cancer was present in 61% of patients and was more common in patients with iPE compared to sPE (80.2% vs 45.2%, p<0.001). Patients with iPE were less likely to have previous VTE (8.2% vs 25.5%, p< 0.0001) and tended to have lower BMI (mean 28.8 vs 31.4, p<0.0001) Characteristics of the subgroup of only cancer patients with PE are summarized in the Table. Of note, pancreatic and GI cancers were more common in patients with iPE. There were no differences in recurrent VTE, major bleeding and CRNMB in patients with iPE compared to sPE. This also held true for patients with underlying malignancies. Mortality rates were significantly higher in all patients with iPE even when adjusting for presence of malignancy (p=0.03). When adjusting for presence of metastatic malignancy though the difference was no longer present (p=0.33). Conclusion: Patients with iPE were more likely to have an underlying malignancy, potentially due to higher likelihood of undergoing staging imaging studies. Additionally, patients with iPE more often had metastatic disease which was associated with higher mortality. Recurrent VTE and bleeding outcomes were similar in patients with iPE and sPE, this was independent of the presence of underlying malignancy. Disclosures McBane: BMS: Research Funding.

Abstract Background Venous stenosis is a well-recognized complication of transvenous leads when patients require lead revisions or device upgrade. In these cases, balloon venoplasty or alternative venous access with subcutaneous tunneling can be performed. Purpose Compare the outcomes of venoplasty vs. tunneling in patients requiring additional transvenous lead implantation. Methods A single center retrospective cohort study of all patients undergoing lead implantation/revision requiring venoplasty or tunneling from 2005–2017. Chi-squared and Wilcoxon Rank-Sum tests were used to compare categorical and continuous variables. Results Ninety five patients met our inclusion criteria (60 venoplasty & 35 tunneling). There was no difference in procedure success rates (p-value=0.98). Tunneling was associated with less fluoroscopy time but higher incidence of acute complications (0% vs. 23%, p-value=0.002) most requiring invasive intervention and/or blood product transfusion. Long term outcomes were comparable and related to lead failure or infection. Outcomes for tunneling vs. venoplasty Variable Tunneling (n=35) Venoplasty (n=60) p-value Age Y 67 (23–84) 70 (29–91) 0.25 Male (%) 24 (69%) 41 (68%) 0.98 Number of existing leads 2.1 (1–4) 2.4 (0–4) 0.1 Age of oldest lead 7.0 (0–21) 7.2 (0–33) 0.73 Number of new leads 1.2 (1–3) 1.4 (1–3) 0.26 Fluoroscopy time (SD) min 29.2 (21.3) 39.7 (21.5) 0.012 Procedure success (%) 35 (100%) 55 (92%) 0.9 Acute complications (%) 8 (23%)1 0 (0%) 0.0002 Pocket hematoma/bleed 4 (11%)2 Hemothorax 2 (6%)3 Pericarditis 1 (3%) Lead compromise 1 (3%) Follow up M 18 (0–76) 28 (0–98) N/A Long term lead issues (%) 6 (17%) 10 (17%) 0.95 Long term complication requiring intervention 4 (11%) 8 (13%) N/A Procedure success: functional lead placed as a result of venoplasty or tunneling. 1Two patients required blood products. 2Two patients required invasive intervention. 3One patient required chest tube and the other ICU admission. Conclusions Balloon venoplasty is associated with similar rates of success and a less incidence of acute complications when compared subcutaneous tunneling. Acknowledgement/Funding NIH T32 Training Grant HL07111-40

Abstract Background: Randomized control trials (RCT) have examined the safety and efficacy of direct oral anticoagulants (DOACs) compared to dalteparin in patients with cancer-associated thrombosis (CAT). Increased major bleeding (MB) was seen with edoxaban and increased clinically relevant non-major bleeding (CRNMB) was seen with rivaroxaban and there has been specific concern about increased risk of bleeding among patients with gastrointestinal malignancies (GIM). Results from RCTs comparing apixaban to dalteparin in CAT are pending. Objective: Using the Mayo Clinic VTE registry, we examined the rates of MB, CRNMB, and overall bleeding (MB + CRNMB) in patients with GIM treated with anticoagulation for CAT. Methods: Consecutive patients treated for CAT were enrolled into Mayo Clinic VTE Registry between March 1, 2013 and July 27, 2018 and were followed prospectively for safety and efficacy. Clinical, demographic and imaging data were collected from each participant at the time of study recruitment. Cancer type, stage, and treatment with chemotherapy were recorded. Major and CRNMB events were evaluated at 3-month intervals. Clinical status was assessed by written questionnaire in subjects unable to return at 3 months. Unreturned questionnaires were followed up with a scripted phone interview. The study was approved by Mayo Clinic Institutional Review Board. Results: In the 535 subjects in the registry with CAT, the mean age (64.6 vs. 62.8 years), mean BMI (28.4 vs. 28.8), and percent female (46.4% vs 40.6%) were numerically similar between DOAC and LMWH treatment groups (Table 1). Metastatic disease was present in 53.6% and 60.2% and chemotherapy was being administered in 66.5% and 71.2% of DOAC and LMWH treated patients, respectively. Thrombocytopenia (<100x109/L) at initiation of anticoagulation was present in 6.8% of DOAC treated and 7.5% of LMWH treated patients. Among all cancer patients, 110 (21%) patients had a GIM, 58 (53%) were treated with LWMH and 52 (47%) were treated with a DOAC (42% rivaroxaban or 58% apixaban). In all CAT, the rate of MB was similar in DOAC versus LMWH treated patients (7.8 vs. 5.4 per 100 person-years; HR 1.48, 95% CI 0.72-3.05; Table 2). The rate of CRNMB however, was significantly increased in the DOAC patients compared to LMWH treated patients (6.18 vs. 0.44 per 100 person-years; HR 14.7, 95% CI 1.92, 112.26). In the sub-group of patients with GIM, the rate of MB was non-significantly higher in the DOAC versus LMWH treated patients (11.1 vs. 3.9 per 100 person-years; HR 2.90, 95% CI 0.57, 14.73). In contrast to the overall CAT group, the rate of CRNMB was similar in the DOAC compared to LMWH treated patients (2.10 vs. 1.92 per 100 person-years; HR 1.18, 95% CI 0.07, 20.21). In GIM patients, apixaban compared to rivaroxaban had a numerically higher, but non-significant, rate of major bleeding (23.98 vs. 3.50 per 100 person-years; HR 4.0, 95% CI 0.54-29.87). In the overall group of CAT, the risk of major bleeding was similar between apixaban and rivaroxaban (9.51 vs. 6.77 per 100 person-years). Conclusion: In our registry of subjects with CAT, we identified a significantly increased rate of CRNMB and overall bleeding, but not MB with the use of DOACs. In our data, GIM alone does not appear to account for the increased bleeding risk seen in CAT with DOACs, as we demonstrated no significant increase in major, CRNMB, or overall bleeding compared to LMWH. Direct comparison between apixaban and rivaroxaban was limited by sample size and number of events. Disclosures No relevant conflicts of interest to declare.

Abstract Abstract 3404 Background: Appropriate periprocedural management of the chronically-anticoagulated patient with an inherited or acquired thrombophilia is uncertain. Objective: To estimate the 3-month cumulative incidence of thromboembolism (TE) and major bleeding and test thrombophilia as a potential predictor of these outcomes among chronically-anticoagulated patients undergoing a procedure. Methods: 2182 consecutive patients referred to the Mayo Thrombophilia Center for standardized peri-procedural anticoagulation management were followed for TE, major bleeding and survival. The three-month cumulative incidence rates for TE, major bleeding and death were estimated by Kaplan-Meier analyses. For each chronic anticoagulation indication, we tested “strong” thrombophilia (antithrombin, protein C or protein S deficiency, homozygous or combined heterozygous Factor V Leiden or prothrombin G20210A), ”weak” thrombophilia (heterozygous Factor V Leiden or prothrombin G20210A), lupus anticoagulant/antiphospholipid antibodies and bridging heparin as potential predictors of TE and major bleeding using Cox proportional hazards modeling. Results: Patients with thrombophilia tended to be younger with a slight female predominance. Compared to no thrombophilia, thrombophilia patients (n=202; 143 bridged with heparin) had similar rates of venous (0% vs. 0.5%; p=0.34) and arterial (0.5% vs. 0.5%; p=0.94) thromboembolism, major bleeding (2.0% vs. 2.0%; p=0.97) and mortality (1.5% vs. 2.2%; p=0.52). Among thrombophilia patients, the TE and major bleeding rates were similar for strong (n=29) or weak thrombophilia (n=99), or lupus anticoagulant/antiphospholipid antibodies (n=74). Similarly, among thrombophilia patients, bridging heparin did not affect the rates of major bleeding (2.1% vs. 1.7%; p=0.85) or TE (0.7% vs. 0%, p=0.52). Conclusions: Inherited or acquired thrombophilia does not appear to impact the rates of TE, major bleeding or mortality after temporary interruption of chronic anticoagulation for an invasive procedure. Disclosures: No relevant conflicts of interest to declare.

Abstract Background Diffuse large B cell lymphoma (DLBCL) with high-risk features carries a poor prognosis despite treatment with immunochemotherapy regimen incorporating rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP). Hence, dose adjusted rituximab, etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin (DA.R-EPOCH), a higher intensity regimen, is suggested as an upfront treatment of high-risk DLBCL. In our study, we analyzed the outcomes in a prospectively followed cohort of patients with de novo high-risk DLBCL who received DA.R-EPOCH, and compared them to the patients who received R-CHOP. Furthermore, we conducted a cost analysis to determine which of the two treatments produces a larger financial burden. Method Patients diagnosed with DLBCL who received chemo-immunotherapy at our center between January 2011 to December 2016 were included in the analysis. High-risk DLBCL was defined by the presence of any of the following features at diagnosis: NCCN- IPI score ≥4, tumor measuring ≥5 cm, MYC ± BCL2 or BCL6 rearrangement by FISH or MYC overexpression (>40% by immunohistochemistry [IHC]), Ki-67 index ≥80% and non-GCB immunophenotype by Hans algorithm. Responses were evaluated at middle and end of chemotherapy. Overall (OS) and progression free survival (PFS) were calculated. For the cost analysis, standardized costs were obtained from Mayo Clinic Florida cost data warehouse based upon patient encounters and treatments. Report cost-to-charge ratios were multiplied by the charges for all hospital billed services, and all resulting costs were adjusted to 2016 dollars with the Gross Domestic Product (GDP) Implicit Price Deflator. Patients who did not receive their complete planned treatment at our facility were excluded from the cost analysis. Results Of 80 patients with high-risk DLBCL, 52 (65%) patients were treated with R-CHOP and 28 (35%) with DA.R-EPOCH. The median follow-up was 11.2 months (range: 0.7- 151.3 months). The planned treatment completion rate and complete remission rate at the end of treatment were similar in both groups. There was no significant difference in OS and PFS among the patients treated with DA.R-EPOCH compared to R-CHOP. The hazard ratio (HR) for PFS was 0.79 (95% CI- 0.28-2.29, P=0.67) and OS was 0.86 (95% CI- 0.26-2.78, P=0.80) (Figure 1). In Cox-regression analysis, low baseline albumin, ECOG performance status ≥2, above-normal LDH, high NCCN- IPI and low cumulative chemotherapy doses were associated with poor OS and PFS. Overall incidence of grade ≥ 3 neutropenia, neuropathy, and unplanned hospitalizations were similar between the two treatment groups. Patients treated with DA.R-EPOCH required more red cell transfusions during the treatment (P=0.004). The total mean cost associated with DA.R-EPOCH and R-CHOP regimens was $106,940 ± $39,351 and $58,509 ± 24,588, respectively (P<0.001). The cost associated with hospital services, laboratory testing and evaluation and management were higher in DA.R-EPCOH group compared to R-CHOP group (P<0.001) (Table 2). Conclusion Our study showed that there was no significant difference in PFS and OS of patients with DLBCL with high-risk features when treated with R-CHOP compared to DA.R-EPOCH. DA.R-EPOCH was associated with higher red cell transfusion requirement and treatment related expenses. A prospective randomized comparison is warranted between these two regimens specifically for patients with high-risk DLBCL. Disclosures No relevant conflicts of interest to declare.

Abstract Abstract 491 Introduction: Chronically-anticoagulated patients with active cancer (Ca) often require temporary interruption of warfarin for an invasive diagnostic or therapeutic procedure. While such patients may be at increased risk for periprocedural thromboembolism and bleeding, there are virtually no estimates of these outcomes among Ca patients or the most appropriate periprocedural anticoagulation management. The aims of this study were to estimate rates of these outcomes among Ca patients and to test active cancer and “bridging” low molecular weight heparin (LMWH) as potential predictors of these outcomes. Patients and Methods: In a retrospective cohort study, all chronically-anticoagulated patients referred to the Mayo Clinic Thrombophilia Center for periprocedural anticoagulation management over the 11-year period, 1997-2007, were followed forward in time for the outcomes of venous and arterial thromboembolism (VTE; ATE), major bleeding and vital status within 3 months of consultation. Warfarin was stopped 4-5 days prior to the procedure and patients received bridging LMWH according to the estimated risk of thromboembolism and bleeding. All outcome events were centrally adjudicated using pre specified criteria. Results: The total cohort (n=2517) included 500 patients with Ca. Chronic anticoagulation indications included prior VTE (n=1033), mechanical heart valve (n=669), atrial fibrillation (n=530) and other (mainly vascular bypass; n=285). 65% and 64% of patients with and without Ca received bridging LMWH, respectively. Prior VTE was more common among Ca patients compared to those without CA, both in the bridged (56% vs 37%; p<0.001) and the non-bridged (48% vs 39%; p<0.05) groups. The 3 month rate for the composite of VTE, ATE or bleeding was higher among Ca patients compared to patients without Ca (5% vs 2%; p=0.004) due to higher post procedure rates of VTE (1% vs 0.2%; p<0.001) and major bleeding (4% vs 1.7%; p=0.009); the post procedure ATE rates were low in both groups (0.40% vs 0.45%). For the entire cohort, patients receiving bridging LMWH had a significantly higher rate of post procedure bleeding (5% vs 1%; p<0.05). Finally, there were significantly more deaths in Ca patients compared to non-Ca patients (5% vs. 1%; p<0.001). Conclusions: The three-month rates of VTE, major bleeding and death among patients with Ca in whom anticoagulation is temporarily interrupted for an invasive procedure is significantly higher than in patients without Ca, especially the major bleeding rate. Use of heparin increases this rate even farther, suggesting that bridging should be used with caution in patients with active cancer. Disclosures: No relevant conflicts of interest to declare.