Slusser, Joshua P.

Introduction: One million patients around the world have had total hip arthorplasty with 35% of them having metal-on-metal implants. Although there have been some case reports of cobalt cardiotoxicity from arthroprosthetic cobaltism resulting in dilated cardiomyopathy, incidence of cardiomyopathy and mortality in these patients is unknown. Objective: We therefore sought to determine the incidence of new onset cardiomyopathy (EF <40%) and associated mortality, in patients with metal hip arthroplasty. Methods: We retrospectively examined the records of the patients form our institutional total hip arthroplasty registry (Metal on Metal: MoM, Metal on Polyethylene: MoP, Ceramic on Ceramic: CoC and Ceramic on Polyethylne: CoP). Among 122 patients with baseline and follow up echocardiograms, cobalt and chromium levels were available in 12 patients, none of which developed incident cardiomyopathy. Results: The mean age of the population with metal group (MoM and MoP) was 53 years, predominantly males. During the follow up period of 10 years, the cumulative incidence (KM curve probabilities) of low EF <=40% in our study population was 14% in metal group as compared to 5% in non-metal group (CoC and CoP), (p value 0.51). At 15 years of follow up, among 122 patients, there were16 deaths in the metal group (81) and only 2 deaths in the non-metal group (41) (p value 0.15). Conclusions: In conclusion, although the incidence of cardiomyopathy as well as mortality is low in patients with metal hip arthroplasty and not significantly, further studies maybe needed to assess its effect on diastolic dysfunction.

Background: Worldwide, approximately one million patients have had total hip arthroplasty with 35% being cobalt and chromium Metal-on-Metal (MoM) or Metal-on-Polythelene (MoP) implants. Animal models have suggested that cobalt and chromium can affect all chambers, but there seems to be an atrial predilection. There are several case reports of metal containing hip arthroplasty causing atrial arrhythmias but the true incidence of atrial fibrillation associated with metal hip arthroplasty remains undefined. Objective: We sought to determine the incidence of atrial fibrillation in patients with metal containing hip arthroplasty. We also examined the association between serum cobalt and chromium levels and arrhythmias in this cohort and all cause mortality. Methods: We retrospectively examined the records of patients from the Mayo Clinic total hip arthroplasty registry (Metal group - Metal-on-Metal: MoM and Metal-on-Polyethylene: MoP, Non-Metal group - Ceramic-on-Ceramic: CoC and Ceramic-on-Polyethylne: CoP) to obtain demographic data, comorbidities, laboratory, ECG, and echocardiographic data. Out of a total of 1756 patients, Cobalt and Chromium levels were available in 138 patients. Results: The mean age of patients with metal containing hip replacement was 50 years and were predominantly male. During a follow up period of 10 years, the incidence of atrial fibrillation in our study population was 8% in metal group compared to 2% (p=0.11) in non-metal group. There was no association between cobalt or chromium levels with the incidence of atrial fibrillation. All-cause mortality was significantly higher in metal group versus non-metal group (p=0.005). Conclusion: The incidence of atrial fibrillation was relatively more in patients with metal versus non-metal hip arthroplasty but there was no association of serum cobalt or chromium levels with incidence of atrial fibrillation in the subset of patients. In addition, all-cause mortality was significantly higher in the metal group suggesting potential toxic effects of metal containing hip arthroplasty.

Background: Cardiovascular disease (CVD) remains the leading cause of death for African-American (AA) adults. There is a low prevalence of ideal cardiovascular health (CVH) (as defined by the American Heart Association’s Life’s Simple 7 TM (LS7)), especially diet, physical activity and obesity among AAs placing them at a disproportionately high risk for CVD. The identification of psychosocial stress that may influence ideal CVH could assist in the development of more effective behavior change interventions among AAs. Objectives: The aim of this study is to examine the associations of multidimensional stressors (chronic stress, minor stressors, and major life events - MLEs) with the LS7 components (classified as poor, intermediate and ideal) in AAs. We hypothesize that stress is negatively associated with the likelihood of achievement of intermediate/ideal levels of the LS7 components and LS7 composite score after adjusting for traditional socio-demographic factors. Methods: Using the Jackson Heart Study (JHS), a cohort of AAs based in Jackson, Mississippi (n=4383), we conducted a cross-sectional analysis of the association of stress measures with LS7 components (smoking, diet, physical activity, body mass index, blood pressure, total cholesterol and glucose). This association was measured using logistic regression which assessed the odds ratios (OR, 95% confidence interval (CI)) of the achievement of intermediate/ideal levels of CVH with progressive adjustment for demographic, socioeconomic, behavioral and biomedical factors. A composite LS7 score was calculated [range 0-14; categorized as 0 to 6 (poor), 7 to 8 (intermediate) and 9 to 14 (ideal)]. We also constructed a cumulative stress score as a summation of tertiles of each stress measure (range 3-9). Results: Fewer participants achieved intermediate or ideal CVH for the LS7 components including diet (39%), physical activity (51%) and BMI (47%). Higher chronic stress and minor stressors scores were associated a decreased likelihood of achievement of ideal/intermediate levels for smoking [OR 0.80; 95% CI 0.73-0.88 and OR 0.84; 95% CI 0.75-0.94, respectively). Higher MLE scores were associated decreased likelihood of achievement of ideal/intermediate levels for smoking (OR 0.84; 95% CI 0.76-0.92) and glucose (OR 0.90; 95% CI 0.82-0.98). Those with higher minor stressors and MLE scores were less likely to achieve intermediate or ideal LS7 composite score categories (OR 0.89; 95% CI 0.81-0.97 and OR 0.91; 95% CI 0.84-0.98, respectively). There was no statistically significant association between LS7 composite scores and cumulative stress scores. Conclusions: Our results suggest that key stress measures may contribute adversely to CVH among AAs. These findings provide support for future lifestyle interventions which integrate a focus on alleviating stressors in this high risk population to improve CVH.

Abstract Background: Frailty assessment has often been performed only at baseline in cohort studies. Little is known regarding factors associated with changes in frailty indices over follow up in patients with coronary artery disease (CAD). Methods: Between 11/2008 - 8/2012, 142 community-dwelling adults ≥65 years of age with prior history of CAD (angina or revascularization) participated in a study of frailty assessment at Mayo Clinic Health System in La Crosse, WI. A sample of participants (n=45) were included for frailty re-assessment using the Fried frailty criteria approximately 5 years after their baseline measures. Frailty classification was based on absence of deficits (non-frail), 1-2 deficits (intermediately frail), or 3 or more deficits (frail). Factors associated with a change in frailty indices were studied. Results: There were 45 patients that had a second assessment of frailty indices. At baseline, 24 patients (60%) were not frail while 16 patients (40%) had at least 1 frail feature. At follow up, 20 patients (50%) were not frail while 20 patients (50%) had a frail feature. Those improving were more often being married, had prior revascularization, and were without angina. Interval development of slower gait speed (r = 0.46; p=0.004) and decreased grip strength (r = -0.39; p = 0.01) were associated with worsening frailty. Conclusions: Older adults with CAD are not often frail by standard criteria; however, incident deficits develop during long term follow-up. Spousal support, absence of angina, and change in functional indices are less often associated with frailty features.

Background Intracerebral hemorrhage (ICH) risk is higher in elderly patients with atrial fibrillation on antithrombotic therapy as well as those with cerebral amyloid angiopathy (CAA). We investigated if mortality among patients with atrial fibrillation on antithrombotic therapy presenting with non‐traumatic ICH was influenced by underlying CAA. Methods and Results We used the Rochester Epidemiology Project to identify 6045 patients with atrial fibrillation aged >55 years on anticoagulation or antiplatelet therapy from 1995 to 2016. Seventy‐four patients in this cohort presented with non‐traumatic ICH. Medical records including imaging data were reviewed to identify those with CAA and record baseline variables and outcomes of interest; 38 of our 74 patients (51.4%) (mean age 81.5 years) met Modified Boston Criteria for possible or probable CAA. Twenty‐six of 74 patients (35%) died during the first 30 days while 56 of the 74 (76%) patients died by 10 years follow‐up after index ICH. Overall mortality was not significantly different between the CAA and non‐CAA groups at any point of time during follow‐up ( P =0.89) even amongst patients restarted on anticoagulation +/− antiplatelet (n=19) ( P =0.46) or those patients restarted only on antiplatelet therapy (n=22) ( P =0.66). Three of the 41 patients who restarted on antithrombotic therapy had a recurrent ICH; these 3 patients met criteria for possible or probable CAA. Conclusions Although more than half of our patients with atrial fibrillation on antithrombotic therapy and non‐traumatic ICH met Modified Boston Criteria for CAA, CAA did not significantly influence the high mortality seen in this cohort.

Abstract Introduction: Myeloproliferative neoplasms (MPN) are associated with an increased risk of venous (VTE) and arterial (ATE) thromboembolic events (TE). Anticoagulation needs to be balanced between the risk of incident and recurrent TE and risk of hemorrhage. While data on outcomes of anticoagulation with warfarin in patients with MPN are available, data on safety and efficacy of direct oral anticoagulants (DOACs) in this subgroup are not. Herein, we present outcomes of use of DOACs in patients with MPN at our institution. Methods: In this retrospective cohort study, we searched the Mayo Clinic clinical databases for patients meeting the WHO criteria for MPN who had been prescribed a DOAC between 2011 and 2017. The MPN diagnosis had to have predated the DOAC prescription. Medical records of consenting patients meeting study criteria were reviewed and data on demographics, diagnosis of MPN, indication for DOAC prescription, and their efficacy (incident or recurrent TE) and safety (hemorrhagic events) were abstracted. Results: Over the study period, 19 patients (female = 10) met inclusion criteria. The median age of patients at MPN diagnosis was 67 years (35-83), and 73 years (53-86) at initiation of DOAC. Prescribed DOACs included rivaroxaban (n=12), apixaban (n=6), and dabigatran (n=2) (one patient received rivaroxaban and was switched to apixaban). MPN diagnoses included polycythemia vera (PV) (n=9), essential thrombocythemia and chronic myeloproliferative neoplasm NOS (3 each), chronic myeloid leukemia and myelofibrosis (2 each). Indications for DOAC included thromboembolism (n=13; 68%) (arterial:2 and venous:11), and atrial fibrillation (afib) (n=6; 31%). The median duration of DOAC therapy was 241.5 days (range 13-1879). Five patients were switched from warfarin to rivaroxaban (n=4) and apixaban (n=1) at patient and/or provider preference; the rest were initiated on the DOAC de novo based on provider preference. Of the 19 patients, one patient each experienced a major hemorrhagic and TE event. One patient with PV who was on rivaroxaban for afib required hospitalization for gastrointestinal hemorrhage due to gastritis; DOAC was discontinued following this episode. One other patient with PV had a non-ST elevation myocardial infarction while on rivaroxaban for afib and prior stroke; DOAC was continued. There were no deaths attributable to DOAC use. Discussion: Our limited data suggests that use of DOACs in patients with MPN is feasible with an acceptable balance between risk of hemorrhage and recurrent thrombosis. Additional data on long term outcomes of DOACs in MPNs are needed. Disclosures No relevant conflicts of interest to declare.

Abstract Background: Prothrombin time (PT) and activated partial thromboplastin time (aPTT) are screening tests of hemostasis commonly ordered for anticoagulant therapy monitoring, evaluation of bleeding, screening for acquired or inherited deficiencies of coagulation factors, and preoperative screening. Evaluation of a prolonged PT/aPTT is best accomplished in an algorithmic fashion consisting of mixing studies and factors assays or inhibitor testing as indicated. However, there is little data available on frequency of conditions that may result in abnormalities of PT/aPTT. The Special Coagulation Laboratory (SCL) at our institution offers an algorithmic approach termed Prolonged PT/aPTT Profile (PT/aPTT profile). Aim: To review our institutional experience with PT/aPTT profile testing (indications and outcomes), and to provide clinical correlation of abnormal PT/aPTT tests on patients seen at our institution in an effort to explain common causes of altered hemostatic testing in outpatient clinical practice. Methods: In this retrospective study, following IRB approval, we reviewed the medical records of patients who underwent outpatient PT/aPTT profile testing in the SCL at Mayo Clinic in Rochester, Minnesota between 2010 and 2017. Data abstracted included patient demographics and clinical presentation, indications for testing, use of anticoagulants, medical diagnoses which could potentially influence coagulation, and results of hemostatic testing (Table 1). Statistical analyses were completed using SAS 9.4 (SAS Institute Inc., Cary, North Carolina). Continuous variables are presented as median (range) while discrete variables are summarized as frequency (percentage). Comparisons of clinical characteristics between groups are made using the rank-sum test for continuous variables. Statistical significance is defined as a 2-tailed P value of less than 0.05. Results: A total of 107 patients met our study criteria, 58 (54 %) male, median age 55 years (range 1-89). Indications for testing included prior prolongation of PT (48%), PTT (29%), PT and aPTT (8%) on outside coagulation testing performed in a non-SCL setting, clinical bleeding episodes (10%) and preoperative screening (5%). Patients with established medical diagnoses known to influence coagulation testing including solid tumors, hematologic malignancies, liver disease, renal disease, autoimmune and rheumatologic conditions and pregnancy were documented along with other baseline patient characteristics (Table 1). SCL PT/aPTT profile testing revealed normal results in 29 of 107 (27%) patients on repeat testing while 78 patients warranted further evaluation of which 27 (35%) had an isolated prolonged PT, 28 (36%) had a prolonged APTT and 23 (29%) had prolongations of both PT and aPTT. After further workup and clinical correlation, causes of abnormal outpatient PT/aPTT profile testing were found to be related to an underlying congenital condition in 16 (21%) patients - most commonly factor VII deficiency (9%) and factor VIII deficiency (4%) - acquired conditions in 53 (68%) patients - most commonly anticoagulant therapy effects (31%) and liver disease (21%) - and of unclear etiology in 7 (9%) cases (Table 2). Specifically, the most common cause of an isolated prolonged PT in our study was found to be vitamin K deficiency (37%) whereas elevations in aPTT and both PT/aPTT were most frequently attributed to the effects of anticoagulant therapy (29% and 52% respectively). Other causes of prolongation on PT/aPTT profile testing following clinical correlation were also identified (Table 2). Discussion: While PT and aPTT are commonly ordered tests, there is little evidence regarding epidemiology of testing indications, distribution of test results, and the clinical correlation of test results. Our study demonstrates that abnormalities in hemostatic testing can be attributed to a wide range of causes including artefactual prolongation influenced by pretest variables or marked abnormalities in secondary hemostasis due to inherited and acquired conditions. Strengths of this study include the SCL algorithmic approach to testing to further elucidate coagulation cascade abnormalities to properly characterize conditions that pose severe hemostatic risk while limitations of this study reflect the experience of a single institution and possible referral bias. 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 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.

Objectives The objective was to assess the impact of procedural characteristics on risk of stroke or transient ischaemic attack (TIA) after transcatheter aortic valve replacement (TAVR). Methods We included 370 consecutive patients who underwent balloon-expandable TAVR from 1 November 2008 to 30 June 2014. Procedural characteristics that may be associated with stroke/TIA were assessed. The primary outcome was stroke/TIA at 30 days. A propensity score was constructed using a logistic regression model with 29 parameters. Cox proportional hazards models were used with a propensity score covariate. Results Mean age was 80.9±7.9 years and mean Society of Thoracic Surgeons score was 8.3±5.0. The total number of balloon dilations ranged from 2 to 7. Out of 370 patients, 13 patients (3.5%) suffered stroke/TIA in the first 30 days after TAVR. In univariate analysis, postdeployment balloon dilation (PD) (HR 3.8, 95% CI 1.24 to 11.61; p=0.02) and emergent cardiopulmonary bypass (CPB) (HR 9.66, 95% CI 2.66 to 35.15; p<0.001) were significantly associated with 30-day stroke/TIA. In the multivariable Cox-proportional hazards model, PD (HR 4.95, 95% CI 1.02 to 24.03; p=0.04) and emergent CPB (HR 7.15, 95% CI 1.39 to 36.89; p=0.02) were independently associated with increased risk of 30-day stroke/TIA after adjusting for propensity score, total number of balloon dilations and periprosthetic regurgitation. Conclusion Postdilation as compared with total number of dilations, and emergent CPB were independently associated with increased risk of clinical neurological events in the first 30 days after TAVR. Reduction in balloon postdilation with appropriate valve sizing may reduce the risk of stroke or TIA after TAVR.