Thomas, Colleen S.

Objective: To better evaluate the relationships between training, demographics, and injury, this study sought to define race-related injury risk factors for half- and full-marathon runners. Design: This 3-year, observational cross-sectional study included adults who participated in a half or full marathon. Prerace and 2-week postrace surveys collected data on demographics, training factors, and injuries. Setting: This study took place during a nationally recognized marathon affiliated with a local hospital. Participants: Runners were recruited during the Expo in the days before the race. Postrace surveys were returned by 1043 half marathoners and 624 full marathoners (response rate, 83%). Interventions: This was an observational study; independent variables included demographic data and race year. Main Outcome Measure: The primary outcome was race-related injury that occurred during the race or within 2 weeks after the race. Results: Race-related injuries were reported by 24% of half marathoners and 30% of full marathoners. For half and full marathoners, respectively, significant factors for injuries were previous injury, lower peak weekly training mileage, and lower weekly mileage before race training. Factors significant for only half-marathon injuries were younger age, female sex, shorter distance of longest training run, and no formal training program. Factors significant for only full-marathon injuries were higher body mass index, fewer days running per week, and fewer years of running experience. Conclusions: Previous running injuries, undertraining, and inexperience increased race-related injury risk; women had higher risk than men. Decreased risk of injury was associated with training loads of greater than 23 miles/week for half marathoners and 40 miles/week for full marathoners.

Abstract Abstract 3315 Background: Acquired von Willebrand syndrome (AVWS) is a frequent cause of bleeding in patients with severe aortic stenosis (AS). The goals of this study were to understand the incidence and patterns of bleeding in patients with various degree of AS and identify predictors for bleeding. Methods: Ninety-one patients (59 men, median age 79 years) with mild, moderate or severe aortic stenosis (AS) (n=64) or heart valve replacement (n=27) were studied. Clinically significant bleeding was determined based on the 2008 NHLBI VWD diagnostic guideline (Haemophilia. 2008, 14(2):171–232). We recorded blood counts, vital signs, mean gradient, peak aortic velocity, aortic valve area (AVA) and valve area index (AVAi), time velocity integral ratio (TVI ratio), VWF antigen (VWF:Ag), VWF activity by latex immunoturbidity assay (VWF:Lx), VWF multimer analysis, and closure times of platelet function analysis ADP and epinephrine cartridges (PFA–CADP and –CEPI). VWF high molecular weight multimer (HMWM) losses were graded as normal/mild or severe when compared to pooled plasma samples from normal donors. Associations with bleeding tendency were explored using single variable and multivariable logistic regression models. Results: Of the 91 patients, 29 (32%) were taking warfarin, and 55 (60%) were taking aspirin. None received a thienopyridine. Clinically significant bleeding was seen in 27 (30%) patients with gastrointestinal (GI) bleeding being most common (n=13). Nine patients who bled required hospitalization. Bleeding tendency was more common in patients with a severe loss of HMWM (OR=3.18, 95% CI: 1.06–9.71, P=0.039) and in patients with AS-associated symptoms (OR=3.02, 95% CI: 1.14–8.24, P=0.027). No other echocardiographic, laboratory, or clinical features demonstrated a statistically significant association with bleeding tendency. Conclusion: The incidence of clinically significant bleeding in this population was about 30% with GI being the most common site. Bleeding tendency was associated with severe HMWM loss and AS-associated symptoms. This study underscores the importance of acquisition of a history of bleeding, cardiac symptoms, and VWF multimer analysis in clinical management of AS patients. Disclosures: No relevant conflicts of interest to declare.

Abstract Abstract 3318 Background: Acquired von Willebrand syndrome (AVWS) due to loss of high molecular weight multimers (HMWM), is a frequent cause of bleeding in aortic stenosis (AS), and is reversed by valve replacement. The goal of this study was to explore predictors of AVWS in patients with AS. Methods: A total of 91 patients (59 men, median age 79 years) with AS (n=64) or heart valve replacement (n=27) were included. We recorded peripheral blood count, vital signs, mean gradient (MG), peak velocity (peak vel), aortic valve time velocity integral (AV-TVI), aortic valve area (AVA) and valve area index (AVAi), time velocity integral ratio (TVI ratio), VWF antigen (VWF:Ag), VWF activity by latex immunoturbidity assay (VWF:Lx), VWF multimer analysis, closure times of platelet function analyzer ADP and epinephrine cartridges (PFA-CADP and –CEPI). HMWM losses were graded as normal, mild or severe when compared to HMWM analyses of pooled plasma samples from normal donors. Potential predictors of HMWM loss were explored using logistic regression analysis. Results: Of the 91 patients, 42 (46%) had loss of HMWM (23 mild and 19 severe). In single variable logistic regression analysis, AVWS was associated with a low AVA (<1.0 cm2; OR=5.08, P<0.001), and low AVAi (<0.60 cm2/m2; OR=5.54, P<0.001), low TVI ratio (<0.25; OR=10.80, P<0.001), prolonged PFA-CADP (≥121 sec; OR=6.76, P<0.001), and low VWF:Lx/Ag (≤0.8; OR=8.06, P=0.008). Moderate peak vel (3–4 m/sec) and high peak vel (>4 m/sec) were associated with loss of HMWM (OR[vs. <3 m/sec]=5.80 and 37.70 respectively, P<0.001) as were moderate MG (25–40 mmHg) and high MG (>40 mmHg), (OR [vs. <25mmHg]=4.50 and 32.50 respectively, P<0.001). In exploratory multivariable analysis, mean gradient remained one of the strongest predictor of loss of HMWM. The estimated sensitivity of MG (≥25mmHg) in diagnosing AVWS was 83% (35/42, 95% CI: 69%-93%) and estimated specificity was 71% (35/49, 95% CI: 57%-83%). Considering the very strong correlation with mean gradient, we also considered the diagnostic utility of peak vel. Peak vel≥ 3 m/sec had a sensitivity of 89% (38/42, 95% CI: 77%-97%) and a specificity of 59% (29/49, 95% CI: 44%-73%) in detecting loss of HMWM. Conclusion: Our data suggest that mean gradient (>25 mmHg) and peak vel (≥ 3 m/sec), both derived from the Doppler aortic valve velocity envelope, are accurate predictors for AS-AVWS, and should be incorporated into algorithmic approaches to laboratory screening for AVWS. Disclosures: No relevant conflicts of interest to declare.

Abstract Introduction: Recent reports have utilized von Willebrand factor (VWF) multimerquantitation in the assessment of native cardiac lesions and prosthetic valve dysfunction. However there is no standardized method for quantitation. We compared 3 methods of assessment which utilized a normal plasma control. Methods: We analyzed 476 samples and their control plasma from 395 patients including normal subjects, patients with aortic stenosis, hypertrophic cardiomyopathy, mitral or aortic regurgitation, normal and abnormal left cardiac valve prostheses, and left ventricular assist device therapy (LVAD). VWF multimers were assessed as normal or abnormal, or as normalized (patient / normal plasma) VWF multimerratios of gel bands >15/2-15 (NMR 15) or gel bands > 10/2-10 (NMR 10). We tested whether one technique was more strongly associated with hemodynamic severity of the cardiac lesion, with a history of acquired bleeding, and compared the results to a separate test of VWF function, platelet function analyzer 15 00 (PFA). Results: Two hundred seventeen patient samples reflected normal or mildly abnormal hemodynamics, 111 moderate, and 113 severely abnormal hemodynamics. Abnormal multimers were present in only 19% of samples with normal or mildly abnormal hemodynamics compared to 79% abnormal in the presence of moderate to severe hemodynamic abnormality. The distinction between moderate and severe hemodynamic abnormality was less striking, 65% versus 88% (figure, left). Quantitative NMR values declined with increasing cardiac lesion severity (figure, middle). The two quantitative multimermethods showed similar relationships to lesion severity by ANOVA, r=0.40 (NMR 15) versus r=0.36 (NMR 10), and by Spearman correlation, r=0.68 for NMR 15, and r=0.66 for NMR 10, and PFA results were comparable (all p< 0.001). Bleeding rates were associated with NMR 15, 10 and PFA (Mann-Whitney p<0.001, figure, right). Conclusion: The dichotomous normal / abnormal VWF multimer method appears to distinguish ≥ moderate hemodynamic disruption, whereas there is a continuous relationship between hemodynamic severity and quantitative multimer methods, which may be clinically useful in circumstances in which clinical estimation of lesion severity is challenging, such as with dysfunctional prosthetic valves. Progressive loss of VWF multimersappears to be associated with bleeding, suggesting that quantitative measures may provide incremental value over the dichotomous normal / abnormal designation. Figure Figure. Disclosures Blackshear: Baxalta, Inc: Consultancy, Research Funding.

Abstract Background: Aortic stenosis-associated acquired von Willebrand syndrome (AS-AVWS) is caused by an accelerated degradation of the highest molecular weight von Willebrand factor (VWF) multimers (HMWM). We recently reported that the severity of the HMWM loss correlates with the severity of AS and patients’ bleeding tendency (Am J Cardiol, 2013;111:374-81). As for the missing HMWM, it is still uncertain if they are cleared from circulation or redistributed with medium-low MWMs, which can be assessed by VWF propeptide (Pro)/antigen (Ag) ratio. Besides the tedious VWF multimer analysis, it is uncertain if VWF activity by immunoturbidic method (Lx)/ Ag ratio or VWF collagen binding activity (CBA)/Ag ratio can be used as a screening test to predict AS-AVWS. It has been speculated in the literature that VWF:CBA is more sensitive than VWF:Lx for detecting a HMWM loss. Our goal was to exam the laboratory characteristics of various VWF tests in evaluating AS-AVWS and the potential mechanism of HMWM loss. Method: Sixty-six patients (between years 2010-2012, 43% male) with varying degrees of AS (16 mild, 20 moderate, and 30 severe) and separate 21 patients who had aortic valve replacement were assessed with VWF:Ag, VWF:Lx, VWF:CBA, platelet function analyzer collagen plus adenosine diphosphate (PFA-CADP), VWF multimer analysis and multimer ratio by densitometry (Am J Cardiol, 2013;111:374-81) after their echocardiography. The clinical endpoints of this study are AS severity measured by mean gradient (MG) by echocardiography and clinically significant bleeding. Statistical analyses including Spearman rank correlation test, estimation of the area under the receiver operating characteristics (ROC) curve, and Wilcoxon rank sum tests were performed. Results: VWF:Lx and VWF:CBA had strong correlation (Spearman r=0.94, P<0.001), and the correlation of VWF:CBA/Ag and VWF:Ltx/Ag was 0.49, p<0.001). As previously published, in patients with AS, MG correlated with VWF:Lx/Ag (Spearman r = -0.41, p <0.001), PFA-CADP (r = 0.49, p <0.001), and VWF multimer ratio (r = -0.76, p <0.001). MG also correlated with VWF:CBA/Ag (r= -0.38, p=0.002), but not with VWF: Pro/Ag (r=-0.20, p=0.12). Among AS and AVR patients, the area under the ROC curve for detection of the loss of HMWM was 0.88 (95% CI: 0.80-0.95) by VWF multimer ratio, 0.76 (95% CI: 0.65-0.86) by PFA-CADP, 0.70 (95% CI: 0.58-0.82) by VWF:CBA/Ag ratio, 0.67 (95% CI: 0.56-0.70) by VWF:Lx/Ag ratio, and 0.53 (95% CI: 0.41-0.65) by VWF:Pro/Ag . In addition to previously published results, clinically significant bleeding, in 14% of AS patients, was not associated with VWF:CBA/Ag (p=0.25) or VWF:Pro/Ag ratio (p=0.83). VWF: CBA/Ag ratio was significantly lower in patients with severe AS (MG > 40 mmHg) compared to AVR patients (median: 0.84 vs. 1.06, p<0.001), while there was no evidence of a difference in VWF:Pro/Ag (p=0.45). Conclusion: HMWM losses are highly prevalent in patients with moderate to severe AS. Of the VWF tests, PFA-CADP and VWF multimer analysis and ratio had the highest predictive ability for AS-AVWS followed by VWF:CBA/Ag and VWF:Lx/Ag. The VWF:CBA is not overly superior than VWF:Lx for predicting a HMWM loss. The normal VWF:Pro/Ag suggests that AS-AVWS is different from other types of AVWS due to accelerated clearance of HMWM. Disclosures No relevant conflicts of interest to declare.

Background Despite a continued focus on improved cardiopulmonary resuscitation quality, survival remains low from in-hospital cardiac arrest. Advanced Resuscitation Training has been shown to improve survival to hospital discharge and survival with good neurological outcome following in-hospital cardiac arrest at its home institution. We sought to determine if Advanced Resuscitation Training implementation would improve patient outcomes and cardiopulmonary resuscitation quality at our institution. Methods This was a prospective, before–after study of adult in-hospital cardiac arrest victims who had cardiopulmonary resuscitation performed. During phase 1, standard institution cardiopulmonary resuscitation training was provided. During phase 2, providers received the same quantity of training, but with emphasis on Advanced Resuscitation Training principles. Primary outcomes were return of spontaneous circulation, survival to hospital discharge, and neurologically favorable survival. Secondary outcomes were cardiopulmonary resuscitation quality parameters. Results A total of 156 adult in-hospital cardiac arrests occurred during the study period. Rates of return of spontaneous circulation improved from 58.1 to 86.3% with an adjusted odds ratios of 5.31 (95% CI: 2.23–14.35, P < 0.001). Survival to discharge increased from 26.7 to 41.2%, adjusted odds ratios 2.17 (95% CI: 1.02–4.67, P < 0.05). Survival with a good neurological outcome increased from 24.8 to 35.3%, but was not statistically significant. Target chest compression rate increased from 30.4% of patients in P1 to 65.6% in P2, adjusted odds ratios 4.27 (95% CI: 1.72–11.12, P = 0.002), and target depth increased from 23.2% in P1 to 46.9% in P2, adjusted odds ratios 2.92 (95% CI: 1.16–7.54, P = 0.024). Conclusions After Advanced Resuscitation Training implementation, there were significant improvements in cardiopulmonary resuscitation quality and rates of return of spontaneous circulation and survival to discharge.

Abstract Objectives To determine whether use of a patient portal during hospitalization is associated with improvement in hospital outcomes, 30-day readmissions, inpatient mortality, and 30-day mortality. Materials and Methods We performed a retrospective propensity score–matched study that included all adult patients admitted to Mayo Clinic Hospital in Jacksonville, Florida, from August 1, 2012, to July 31, 2014, who had signed up for a patient portal account prior to hospitalization (N = 7538). Results Out of the admitted patients with a portal account, 1566 (20.8%) accessed the portal while in the hospital. Compared to patients who did not access the portal, patients who accessed the portal were younger (58.8 years vs 62.3 years), had fewer elective admissions (54.2% vs 64.1%), were more frequently admitted to medical services (45.8% vs 35.2%), and were more likely to have liver disease (21.9% vs 12.9%) and higher disease severity scores (0.653 vs 0.456). After propensity score matching, there was no statistically significant difference between the 2 cohorts with respect to 30-day readmission (P = .13), inpatient mortality (P = .82), or 30-day mortality (P = .082). Conclusion Use of the patient portal in the inpatient setting may not improve hospital outcomes. Future research should examine the association of portal use with more immediate inpatient health outcomes such as patient experience, patient engagement, medication reconciliation, and prevention of adverse events.

AbstractIntroductionTakotsubo syndrome (TTS), also known as Takotsubo cardiomyopathy or stress‐induced cardiomyopathy, has been described following a variety of surgeries and disease states. The relationship between intra‐operative anesthesia management and the development of this syndrome has never been fully elucidated.ObjectivesThe primary objective of this study was to determine the relationship of multiple intra‐operative factors on the pathogenesis of TTS.MethodsA single‐center retrospective review of all liver transplants performed at Mayo Clinic Florida from January 2005 to December 2014. Patients developing left ventricular dilation and a concomitant decrease in ejection fraction, a negative cardiac catheterization, or stress test within 30 days of transplantation were identified. Cases were matched 2:1 to controls with respect to MELD, age, sex, and indication for transplantation. Our evaluation included liver graft characteristics, intra‐operative medications, and intra‐operative hemodynamic measurements.ResultsWe identified 24 cases of TTS from a pool of 1752 transplants, for an incidence of 1.4%. No statistically significant differences in intra‐operative measures between the two groups were identified (all P ≥ .08).ConclusionOur exploratory, single‐center retrospective review evaluating 46 intra‐operative characteristics found no association with the development of TTS.