Duello, Katherine

Introduction: Elevations of troponin after subarachnoid hemorrhage (SAH) frequently occur and are associated with cardiopulmonary complications. The time to peak elevation remains poorly described in terms of the natural history after SAH. Our two objectives were to define the temporal profile of troponin T elevation after SAH and correlate levels of troponin T with baseline neurological status. We hypothesized that troponin T would peak early after initial presentation. Methods: We reviewed the medical records of all aneurysmal and non-traumatic SAH patients from March 2011-December 2012. Troponin T from patients with ≥ 2 values was recorded with respect to SAH symptom onset. Patients with ≥ 1 Troponin T value were stratified according to admission Glasgow Coma Scale (GCS). GCS was dichotomized to > 8 or ≤ 8. Fisher’s exact test was performed comparing elevated peak troponin T (≥0.01 ng/ml) versus normal against GCS status cutoffs > 8 or 8 or less. Results: We identified 124 patients who had both troponin T and GCS reported, and 30 patients had ≥2 troponin T measurements within the first 40 hours of hospitalization. The median time to peak troponin T in these patients was 11.2 hours with a standard deviation of 6.2 hours (Range: 4.9-35.0 hours). Elevated troponin T was seen in 52 of 124. GCS of ≤ 8 was present in 43 of 124. Patients with elevated levels of troponin T had a greater chance of lower GCS [Odds ratio = 4.8 (95% CI: 2.2 to 10.7)] (P= <0.0001). Conclusions: The median time to peak troponin T after SAH injury was 11 hours. There was a statistically significant association between troponin T elevation and worse neurologic status at presentation (GCS ≤ 8). Although our small sample size found large variation in time to peak troponin, it supports the hypothesis that troponin peaks early after the initial presentation. Future studies using troponin elevation as a biomarker should focus on sample acquisition at the time of admission and in the first 1-2 days.

Abstract Abstract 3377 Background Bleeding from AVWS may occur in aortic stenosis (AS), hypertrophic cardiomyopathy (HCM), mitral regurgitation (MR), and prosthetic valve dysfunction (PVD) due to loss of von Willebrand factor (VWF) high molecular weight multimers caused by shear stress. Traditional laboratory testing for AVWS, including VWF antigen (VWF:Ag) and ristocetin cofactor activity lack sensitivity in this setting, and VWF multimer analysis, a costly and time-consuming test, must be used for confirmative diagnosis. The goal of this study is to develop a clinical and laboratory approach to predict the likelihood of AVWS, and consequently obviate the need for multimer analysis. Methods 160 patients with or without a bleeding history were prospectively enrolled with mild, moderate, or severe AS (n=65), HCM (n=32), MR (n=25), or with heart valve replacement (n=38). These patients were investigated at the time of clinically indicated echocardiography with VWF latex immunoturbidic activity (VWF:Ltx), VWF:Ag, (abnormal versus normal cutoff of VWF:Ltx/VWF:Ag is <0.80) platelet function analyzer 100 collagen ADP (PFA-CADP) and VWF multimer analysis. Single variable logistic regression analysis was performed to estimate clinical or laboratory variables that were strongly associated with the probability of abnormal multimers, including results of echocardiographic peak velocity and PFA-CADP. Associations with abnormal multimers were summarized with estimated relative risk (RR) and 95% CI. A scoring system was then created to evaluate the risk of abnormal multimers among cardiac patients. Results Overall, 50% of patients had abnormal multimers, indicating likely AVWS. The estimated probability of abnormal multimers showed a significant association between peak velocity, PFA-CADP and VWF:Lx/Ag (Table 1). Logistic regression analysis using forward selection identified only peak velocity (p<0.001) and PFA-CADP (p=0.033) as the factors showing the strongest evidence of association with abnormal multimers. VWF:Lx/Ag was no longer significant after adjusting for these two variables. Estimated relative risk of abnormal multimers for values of peak velocity and PFA-CADP were then derived (Table 2). From these relative risks a scoring algorithm was created in order to determine who should be screened for abnormal multimers. A value of 1 was subtracted from each relative risk and rounded to the nearest integer to obtain a score for peak velocity (<3 m/sec=0, 3.0–3.9 m/sec=3, 4.0–4.9 m/sec=5, >5.0 m/sec=7), and for PFA-CADP (≤120 sec=0, 121–180 sec=2, > 180 sec=3). The score from each of the two variables was added to obtain a total score ranging from 0 to 10. The risk score was categorized into four levels, which are 0, 2–3, 5–7, and 8–10, as shown in Table 3. Conclusion Both hemodynamic severity and PFA-CADP testing results could be incorporated into a scoring system to identify potential AVWS due to loss of HMWM in patients with various cardiovascular conditions. Further studies are needed to validate such a scoring system in a separate set of patients. Disclosures: No relevant conflicts of interest to declare.

Abstract Abstract 1128 Background Dysfunctional or mismatched prosthetic heart valves can results in high shear stress related von Willebrand factor (VWF) impairment, and clinical bleeding. This mechanism is similar to that seen in aortic stenosis patients, where gastrointestinal bleeding related to VWF multimer loss is well described (Heyde syndrome). In this study, we compared the results of VWF testing of patients with normally functioning cardiac valve prostheses, dysfunctional prosthetic valves, severe native aortic stenosis, and normal controls. Methods A total of 75 patients, 31 female and 44 male with a median age of 79.5 years were recruited to this study. Thirty patients had severe aortic stenosis (mean gradient > 40 mm Hg); 39 patients had normally functioning prosthetic valves, 21 aortic (AVR) and 18 mitral valves (MVR); and 6 patients had with dysfunctional valves (4 aortic and 2 mitral). Whole blood and plasma samples were drawn from patients and tested for platelet function analyzer-100 collagen ADP closure time (PFA-CADP), VWF antigen (VWF:Ag), VWF activity by latex immunoassay (VWF:Ltx), VWF multimer analysis and VWF multimer densitometry ratio of large vs medium to low molecular weight multimers (>15 mers/2–15 mers). Results The 6 dysfunctional prosthetic valve patients included patient-prosthesis mismatch (2) and (one each), thrombosed mechanical aortic prosthesis, torn biological aortic prosthesis, severe tissue mitral prosthetic regurgitation, and post-mitral valve repair severe mitral regurgitation. Four of six patients had clinically significant bleeding. Most aortic stenosis and all 6 prosthetic dysfunction patients had abnormal VWF multimers which is rare in normally functioning prostheses and completely absent in normal donors. VWF:Ltx/Ag was lower in AS and MVR than normal. VWF:Ltx/Ag ratio, VWF:multimer ratio and PFA-CADP were all significantly abnormal in patients with dysfunctional prosthetic valve. VWF:multimer ratios in normally functioning prostheses tended to be intermediate between normals and than those of patients with severe AS or prosthetic valve dysfunction (Table). Conclusions VWF testing including quantitative von Willebrand multimer analysis and PFA-CADP reliably separate dysfunctional from normally functioning cardiac prostheses, and should be considered in the evaluation of patients with cardiac prostheses, especially those who have clinically significant bleeding. Disclosures: No relevant conflicts of interest to declare.

Abstract Abstract 2230 Background: Heyde syndrome describes patients with severe aortic stenosis (AS) who have bleeding diathesis, especially gastrointestinal bleeding. Although acquired won Willebrand syndrome (AVWS) due to loss of the highest molecular weight multimers (HMWM) presents in most patients with severe AS, not all such patients develop Heyde syndrome. The goal of this study was to explore whether the severity of HMWM loss was significantly associated with Heyde syndrome. Methods: We first performed chart reviews on patients referred for double balloon enteroscopy (DBE) for GI bleeding or iron-deficiency anemia (GIB/FeDefic) in two time periods, from 2005–2008, and from 2009–2011. Next, patients who could have AVWS due to AS or other cardiovascular or hematologic disorders were identified. Laboratory tests including VWF antigen (VWF:Ag), VWF ristocetin cofactor activity or VWF latex immunoturgidic activity (VWF:Ltx) and/or VWF multimer analysis were performed as requested by physicians. From this population, patients with Heyde syndrome were identified. Their clinical and VWF laboratory testing results were compared to a separated group of patients with severe AS patients who had no clinically significant bleeding, but had matched gender and hemodynamic severity by echocardiogram (Matched AS Controls). These patients all had VWF:Ag, VWF:Ltx, and VWF multimers performed. In both Heyde syndrome patients and Matched AS controls, VWF multimer densitometry ratio of the HMWM (>15 mers) to low to intermediate multimers (2–15 mers) was assessed (VWF:multi ratio). Results: Overall, 437 patients underwent DBE for GIB/FeDef. Between 2005 and 2008, 1% of 318 patients had VWF testing. From 2009 to 2011, 23% of 119 patients were tested. Heyde syndrome was noted in 15 patients. Of the 437 patients, 134 patients (31%) likely had AVWS based on diagnoses of moderate-severe AS (30%), moderate to severe mitral regurgitation (25%), moderate to severe pulmonary hypertension (16%), prosthetic valve regurgitation or stenosis (13%), hypertrophic cardiomyopathy (10%), and hematologic disorders (4%). Among these 134 patients, 29 patients had VWF tests performed, and 22 had VWF multimer analysis. VWF antigen levels were similar in Heyde syndrome and Matched AS Controls (176±89% versus 155±77% respectively). Despite similar hemodynamic severity, more severe HMWM loss as indicated by lower VWF:Ltx/Ag and VWF:multi ratios was present in Heyde syndrome patients than matched AS controls (table, P<0.0007). Conclusion: If AVWS is suspected in patients with GIB/FeDef, laboratory testing for VWF indices is important to confirm the diagnosis of AVWS. Despite similar hemodynamic severity, Heyde syndrome patients have more severe VWF HMWM loss indicated by significantly decreased VWF:Ltx/VWF:Ag and VWF:multi ratios. Conversely, though highly sensitive for AVWS, PFA-CADP does not predict bleeding tendency in patients with severe AS. Disclosures: No relevant conflicts of interest to declare.

ABSTRACT Background The Accreditation Council for Graduate Medical Education requires residents to learn and demonstrate proficiency in practice improvement. Quality improvement (QI) projects are a way to improve patient care as well as facilitate education on this core competency. There are inherent barriers to completing these goals in the structure of residency training including rigorous resident schedules and a limited number of projects and resources. Objectives We developed a QI programme using an experiential class project and incorporated it into our Internal Medicine Resident Core Curriculum to improve the residents’ knowledge of QI methods. We assessed the residents’ experience, knowledge and interest in practice and QI subject matter with a survey preimplementation and postimplementation. Methods In 2009, 24 residents in the Internal Medicine resident programme completed a survey measuring their experience, knowledge and interest in QI initiatives. They then completed a QI 1-year programme, with monthly, 1-hour sessions combining didactics and a resident-designed project. At the conclusion of the year, the residents completed the same survey, and the results were compared and analysed. Results Postcurriculum questionnaires revealed residents were more knowledgeable about QI methods, showing improvement in knowledge about institutional-wide QI projects, better preparation for implementing a QI project, and more likely to participate in QI in the future. The project completed was one which improved patients’ knowledge of their anticipated date of discharge from the hospital. Conclusions A class quality project can teach QI to residents incorporating both didactic and practical methods to maximise the experience and minimise the barriers. We found that this method improved residents experience, knowledge and interest in quality initiatives.