bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 220: Early Assessment of Real-world Utilization and Dosing of Sacubitril/Valsartan in the US
Authors: Chang Chun-Lan , Song Xue , Willson Tina , Duffy Carol
Published: June 2021

Background:
Based on the PARADIGM-HF trial, sacubitril/valsartan was approved for the treatment of patients with heart failure and reduced ejection fraction. This study provides an early view of its real-world utilization and dosing in the US before recent guideline updates.

Methods:
Adult patients with >=1 sacubitril/valsartan claim in 7/7/2015 - 3/31/2016 were selected from a large national claims dataset; their 1st sacubitril/valsartan claim was the index date. Data was required for >=24 months pre-index and >=3 months post-index. Dose at index and the maximum dose achieved post-index were obtained. Dose up-titration, defined as 1st appearance of a sacubitril/valsartan claim with a dose increase from the index strength, and the time to 1st dose increase were reported.

Results:
Among 981 qualified patients with a mean follow-up of 185 (SD ±81) days, 25% commenced sacubitril/valsartan on the suggested prescribing information (PI) starting dose of 49/51 mg b.i.d.; 58% started on 24/26 mg b.i.d.; 4% started on an even lower dose, and 13% indexed at the target maintenance dose of 97/103 b.i.d.. The target maintenance dose of 97/103 mg b.i.d. was achieved in 30% of patients. For those 856 patients indexing on <=49/51/ mg b.i.d., 58% had no dose up-titration post-index; 31% took >4 weeks to have up-titration initiated and 11% initiated up-titration within 4 weeks. Only 25% of Medicare patients compared to 35% of Commercial patients achieved the target dose of 97/103mg b.i.d.. (Table 1)

Conclusion:
Most patients commenced sacubitril/valsartan at lower doses than recommended in the PI and were poorly optimized, with the majority of patients having no upward dose titration. Approximately 13% actually indexed at the target maintenance dose. The reasons for these findings need further exploration. Healthcare providers should consider following the appropriate starting doses, with timely dose adjustment of sacubitril/valsartan as recommended in the PI to ensure patients receive the full clinical benefit of this medication as demonstrated in the PARADIGM-HF trial.
Abstract 225: A Depression Quality Program and Cardiovascular Disease: Assessing the Impact on Care
Authors: Gordon Linda , Malecky Amanda , Althouse Andrew , Ansani Nicole
Published: June 2021

Background:
Data demonstrate an adverse association between depression and coronary artery disease prognosis. Therefore, a depression screening program was initiated in the catheterization (cath) lab. The goals were to improve HEDIS depression compliance rates and determine the impact on clinical outcomes.

Methods:
Adult patients in an inpatient cath lab from 3 cardiology practices were screened for enrollment in a randomized controlled trial. All cath lab patients received a PHQ-9 depression screener. Those who screened positive for depression (score ≥ 10) were randomized to intervention or usual care. The usual care group received a follow-up phone call to re-administer the PHQ-9 at 6-8 weeks and within 210 days of discharge. The intervention group was administered the PHQ-9 and received intensive education at baseline, 6-8 weeks, and within 210 days of discharge. Education included targeted depression information with a mental health care provider and comprehensive disease management education with a cardiovascular nurse practitioner. Outcomes included: differences in HEDIS depression goal attainment; depression response/remission rates; and cardiovascular goals. Differences between groups were tested using chi-squared tests (categorical variables) and t-tests (continuous variables).

Results:
Baseline characteristics were similar between control (N=43) and intervention (N=40) groups, with the exception of significantly fewer African American patients in the control group (N=2, 4.7%) vs intervention (N=9, 22.5%). Changes in HEDIS goal attainment show that patients in the intervention group were slightly more likely to be referred to a provider to address depression (95.0% vs 86.0%, p=0.314), or receive meds for depression (65.0% vs 51.2%, p=0.219), but these differences are not statistically significant. More patients in the intervention group refused meds for depression compared to control (15.0% vs. 2.3%, p=0.041); have received blood work (65.0% vs 41.9%, p=0.030); and have received follow-up within 210 days (82.5% vs 46.5%, p<0.001). Treatment adjustment rate was higher in the intervention group compared to control (85.0% vs. 65.1%, p=0.037). Hospital readmission rate was similar between groups (p=0.896) and there was no difference in depression remission or response rates (p=0.426). Further, no differences were seen in cardiovascular surrogate outcome parameters, including cholesterol, A1c, CRP, or BNP between groups; except SGOT was significantly different between groups (-5.0 intervention vs 2.0 control p=0.045).

Conclusions:
These data demonstrate improvements in attaining a surrogate outcome measure of quality (HEDIS goals); however, this does not appear to translate to a significant clinical impact. Quality measures may need to be continuously reassessed to ensure efficiency and effectiveness of care.
Abstract 227: Healthcare Cost Impact of Continued Anticoagulation With Rivaroxaban Versus Placebo in the EINSTEIN-Extension Trial Population
Authors: Wells Philip S , Lensing Anthonie W , Haskell Lloyd , Levitan Bennett , Laliberté François , Durkin Mike , Ashton Veronica , Xiao Yongling , Crivera Concetta , Lejeune Dominique , Schein Jeff , Lefebvre Patrick
Published: June 2021

Background:
The EINSTEIN-extension trial (EINSTEIN-EXT) found that continued treatment with rivaroxaban for an additional 6 or 12 months (versus placebo) after the initial 6-12 months of anticoagulation significantly reduced the risk of recurrent venous thromboembolism (VTE) with a small increased risk of major bleeding (none was fatal or in a critical site). This study aimed to assess the cost impact of rivaroxaban vs. placebo based on EINSTEIN-EXT recurrent VTE and bleed rates.

Methods:
Total costs were calculated as the sum of drug and clinical event costs, and compared between cohorts from a US managed care perspective. Treatment duration and event rates were obtained from EINSTEIN-EXT. Drug costs were based on wholesale acquisition costs. Cost estimates for clinical events (i.e., recurrent VTE, major bleeding, clinically relevant nonmajor bleeding, and mortality) were determined based on a targeted literature review. Results were examined over a ± 20% range of each cost component in a one-way sensitivity analysis approach.

Results:
Total cost per person was $1,161 lower for rivaroxaban (vs. placebo) in the base case, with lower cost of clinical events fully offsetting drug costs (Figure 1). The difference in recurrent DVT alone (-$3,102) was greater than drug cost ($3,025). Total cost of rivaroxaban remained lower than placebo in sensitivity analyses.

Conclusions:
Rivaroxaban is associated with lower total costs compared to placebo in VTE patients who had completed 6 to 12 months of VTE treatment.
Abstract 229: Real-world hsCRP Testing, With a Potential to Evaluate Residual Inflammatory Cardiovascular Risk, Among Patients With History of Myocardial Infarction in the United States: A Retrospective Database Analysis
Authors: Deschaseaux Celine , Sharma Puza , Gabrielsen Anders , Siadimas Athanasio , Bauer Melissa , Przybysz Raymond
Published: June 2021

Background:
C-reactive protein can be measured by a high-sensitivity assay (hsCRP) to detect persistent low grade vascular inflammation predictive of cardiovascular (CV) risk in patients with history of myocardial infarction (MI). However, the real-world use of hsCRP testing among patient with history of MI, and hence the contemporary usage to address residual inflammatory risk, is unknown

Methods:
Patients with ≥1 claim with an inpatient, primary diagnosis for MI (ICD-9-CM code: 410.xx) between 01 October 2011 to 30 September 2014 (the most recent set as an index) in MarketScan and 1 year continuous enrolment pre- and post-hospital admission were included

Results:
A total of 71,071 patients (mean age 63.6 years, 67.6% males) were included. The hsCRP measurement was performed in 3.3% patients (CCAE: 4.7%; Medicare: 1.3%) with a mean time of 4.3 months after the index MI; 81.7% of patients were tested ≥30 days after the index MI. Patient characteristics and resource uses were similar among hsCRP tested and non-tested patients (Table 1)

Conclusion:
hsCRP testing with a potential to evaluate residual inflammatory CV risk is not used widely in routine clinical practice in US patients with history of MI. No systematic effect of hsCRP testing was observed with respect to patient characteristics and resource use. Further research is warranted to understand and describe the real-world usage of hsCRP testing to evaluate residual inflammatory risk and the associated patient characteristics, outcomes and burden of disease
Abstract 231: Single Site Lifestyle Survey in FMD Patients Suggests Improvement Over Time
Authors: Bumpus Sherry M , Heidt Steven T , Krallman Rachel , Kline-Rogers Eva
Published: June 2021

Background:
Fibromuscular dysplasia (FMD) is a polyvascular disorder that may result in narrowing, aneurysm, or dissection of affected arteries. A recent qualitative study illuminated common themes relative to being diagnosed and living with FMD. This study sought to quantitatively explore these themes in a larger sample.

Methods:
Patients from a single site in the US Registry for FMD (USRFMD) were eligible to participate. Subjects received an initial survey packet and up to two reminders between July and September 2015; surveys were returned via U.S. mail or online. Surveys were linked to the USRFMD database, from which clinical data was drawn. The survey included valid and reliable instruments including the Patient Health Questionnaire (PHQ) 9, PHQ-15, and the Generalized Anxiety Disorder Questionnaire.

Results:
Of 91 surveys mailed, 72 were completed (79.1%). Most respondents were female (94.4%, n=68) and white (97.2%, n=70), with a mean age at diagnosis of 52.7 ± 11.9 years and had been living with FMD for a mean of 9.7 ± 8.1 years. Medical history did not differ significantly between participants and non-participants. Screening showed that 21.7% of patients experienced moderate depression, 40.7% experienced significant physical symptoms, and 10.4% experienced moderate generalized anxiety. Though not statistically significant, there was a trend towards reduced mental health symptoms over time (Figure 1) and higher symptomatology with treatment delays of 1-5 years (data not shown). No differences were found in mental health based on number or location of vessels affected by FMD. Patients who had experienced an adverse event (e.g. stroke, TIA, MI, dissection, renal infarction, mesenteric ischemia) reported more physical symptoms (57.1% v. 23.1%, p=.014).

Conclusion:
Among patients from a single center participating in the USRFMD, rates of anxiety and depression are nearly double that of the general population. Trends indicate that depression, physical symptoms, and anxiety may decrease over time. Given the higher rates of anxiety, depression, and somatoform symptoms compared to the general population, greater efforts are needed to make earlier diagnoses and support patients, particularly in the early stages post-diagnosis.
Abstract 236: Coronary Artery Procedures in the Cardiac Catheterization Laboratory After Overnight Call: Are Patients at Higher Risk?
Authors: Boudoulas Konstantinos Dean , Pederzolli Andrew , Nagaraja Haikady , Kahaly Omar , Magorien Raymond , Mazzaferri Ernest
Published: June 2021

Background:
Overnight call can lead to sleep deprivation and fatigue. It was hypothesized that complications will increase when coronary artery procedures are performed the day after overnight call (i.e. post-call). The present study was undertaken to test this hypothesis.

Methods:
From June 2009 to May 2013, >20,000 patients underwent a cardiac procedure in a large referral catheterization laboratory of which 10,190 patients (12.7%, n=1,298 post-call) underwent only coronary arteriography with (37%) or without (83%) percutaneous coronary intervention (PCI) with no other cardiac procedure(s). Procedural complications related to post-call status were determined.

Results:
Mean age was 61±12 years (male 65%). Overall complications were 2.6%: 1.0% bleeding, 1.0% myocardial infarction (MI), 0.3% new dialysis, 0.3% heart failure, 0.1% cardiogenic shock, 0.2% vascular, 0.1% stroke and 0.01% cardiac tamponade (certain patients had >1 complication). Overall there was statistically greater procedural complications when performed post-call (3.5%) compared to no post-call (2.5%; p=0.04); however, when adjusting for significant baseline variables, there was no difference seen between groups. From multivariate analysis of 23 factors, the following contributed independently to complications: ST-elevation MI (odds ratio 4.2, confidence interval [CI] 2.3-7.1), femoral vs. radial access (odds ratio 2.4, CI 1.7-3.3), non-ST-elevation MI (odds ratio 2.1, confidence interval [CI] 1.6-2.7), PCI (odds ratio 2.1, CI 1.6-2.7), history of heart failure (odds ratio 1.6, CI 1.2-2.1), female (odds ratio 1.4, CI 1.1-1.8), and age (odds ratio 1.2, CI 1.1-1.3 per 10 years). Glomerular filtration rate <60 ml/min was associated with more complications compared to >60 ml/min (p=0.007).

Conclusion:
There were greater procedural complications when performed post-call compared to no post-call; however, when adjusting for significant baseline variables, there was no significant difference seen between groups. Taking into consideration factors that contributed to procedural complications most likely will improve patient outcomes.
Abstract 238: Evaluation of the Satisfaction of Emergency Medical Services’ Staff, Attending Workshops on Maintaining and Improving Professional Skills and Knowledge
Authors: Ursat Cecile , Groizard Charles , Baer Michel , Ozguler Anna , Loeb Thomas
Published: June 2021

Introduction:
to fulfill the needs to maintain professional skills, mainly procedures in unusual on scene situations in the EMS setting, workshops on maintaining and improving professional skills have been set up (MPAP). These workshops are proposed every day to the whole EMS staff (Nurses, physicians, paramedics) The aim of this work is to evaluate the attendees’ satisfaction.

Methodology:
Since November 2015, MPAP are proposed. The attendees’ satisfaction was estimated using an anonymous questionnaire. 9 questions were asked and each answer was quantified on a scale ranging from 1 (total disagreement) to 4 (total agreement).

Results:
104 sessions took place with an average of 11 sessions per month. The average participation was 12 people. Among the 108 questionnaires, 52 physicians, 29 paramedics and 27 nurses answered (53%). Table 1 summarizes the answers to the questions depending on professional category of the attendees. Results are shown as average.

Conclusion:
the excellent average grades confirm the satisfaction of the EMS’ personnel regarding the MPAP session; Maintaining these workshops for continuous education is now one of the EMS main objectives.
Abstract 241: Abstract QCOR 2017
Authors: Mullangi Samyukta , Dawson Taylor , Paluga Elizabeth , Kronick Steven , Nallamothu Brahmajee , Stojan Jennifer
Published: June 2021

AHA QCOR 2017 Abstract submission Category: Cardiac Arrest/CPR

“How well can you run a code?” Assessing resident comfort and competence with in-hospital cardiac arrest

Background:
Despite their frequent role in caring for patients with in-hospital cardiac arrest (IHCA), earlier data suggest residents often feel uncomfortable during resuscitations. We sought to characterize the experiences of residents at our academic institution with IHCA, delineate reasons for discomfort (if any) with their roles, and then assess what educational interventions were considered most valuable.

Methods:
We performed a 9-question survey that was electronically distributed to all internal medicine and medicine-pediatrics residents at the University of Michigan Health System. This survey asked residents about: 1) the number of IHCAs that residents had attended or led, 2) their comfort with their roles including leading an IHCA, 3) possible reasons for any discomfort in their roles, and 4) educational interventions that would be considered favorable. We report simple unadjusted statistics.

Results:
We received 100 responses from 155 residents, a 64.5% yield. Most PGY-1s and 2s reported being to few or no IHCAs (n=47/69, 68%) and that some PGY-3s and 4s had never run a resuscitation effort (n=4/31, 13%). Regardless of level of training, few residents rated their ability to run a resuscitation effort as very good or excellent (n=8, 8%). Most residents were unsatisfied with the formal education currently in place for IHCAs (ACLS training, code refresher sessions for residents on general medicine or cardiology) (n=62, 62%). The majority of residents had rarely or never given (n=72, 72%)/received feedback (n=68, 68%). Of the possible educational interventions presented as options, the most popular that were perceived among residents were debriefing with the attending physician and other residents (n=66, 66%), and debriefing in a multidisciplinary setting (n=59, 59%).

Conclusion:
We characterized the experience of internal medicine and medicine-pediatrics residents with leading IHCAs at our academic institution. We found few residents perceived their own comfort and competence as adequate. These findings provide a foundation for future efforts to potentially elevate resident performance in IHCA.
Abstract 244: Revision of the Consent Form for Coronary Angiography Procedures
Authors: Tavella Rosanna , Halliday Luke , Arstall Margaret , Worthley Matthew , Chew Derek , Zeitz Chris , Beltrame John F
Published: June 2021

Background:
Physicians have a legal and ethical responsibility to provide adequate information to patients so appropriate, informed decisions can be made. Although clinical trial data suggest that the incidence of complications associated with invasive coronary procedures is relatively low, contemporary data from real world, non-trial related populations are lacking, and this has implications for the informed consent process. This study revises the consent form for coronary angiography procedures using clinical registry data.

Methods:
A statewide patient risk information sheet and procedure consent form was developed for patients undergoing coronary angiography and/or percutaneous coronary intervention (PCI) in South Australian (SA) public hospitals (population 1.6 million). The risk information was generated from data obtained via the Coronary Angiogram Database of South Australia (CADOSA), a comprehensive registry of all public angiograms and PCIs performed in SA, compatible with the NCDR® CathPCI® Registry. All consecutive patients undergoing procedures in 2012-2014 were included.

Results:
From 15,121 angiographic procedures performed, 28% were elective (4,234 of 15,121) and 4,617 were PCI (30%). Patients had a mean age of 65±13 years, 34% (5,096 of 15,121) were female and radial access was frequent at 60% (9,032 of 15,121). Procedural complications for angiography (n=10,504) and PCI (n=4,617), respectively were: mortality within 24 hours: 0.06%, 0.45%; stroke within 24 hours: 0.13%, 0.19%; haemorrhagic stroke: 0.03%, 0.04%; emergency CABG: 0.02%; 0.13%; major bleeding: 0.48%, 1.58%; access site bleed: 0.26%, 0.56%; other vascular complications at access site: 0.07%, 0.09%; new onset/worsening heart failure: 0.45%, 0.95%; requirement for dialysis: 0.11%, 0.17%, tamponade: 0.03%, 0.15%; significant dissection during PCI 1.13% and perforation during PCI: 0.19%. The rates of complications were listed in the patient risk information sheet in the form of ‘per number of procedures’ with 1,000 as the denominator for most events.

Conclusion:
In a representative assessment of coronary angiography and PCI outcomes, some major complications are higher that those reported in international literature. Significant access site bleeding was low, likely explained by the high prevalence of radial procedures. Future iterations of the patient information sheet and consent form may be improved by providing personalized risks.
Abstract 246: Length of Stay and Its Association With Get With the Guidelines-stroke Award Recognition
Authors: Hamm Theresa , Overton Angela , Thomas Kathie , Sednew Renee
Published: June 2021

Background and Objectives:
The average length of stay (ALOS) provides important information regarding care efficiency and the financing of hospitals. A shorter ALOS helps to reduce hospital costs, increase capacity optimization, and improve hospital efficiency. A longer ALOS can be associated with reduced readmission rates and mortality rates. The objective of this study was to analyze the ALOS for stroke patients based on etiology subtype and Get With The Guidelines (GWTG)-Stroke award recognition.

Methods:
A retrospective review of the ALOS for hemorrhagic and ischemic stroke patients was conducted for the states of Illinois, Iowa, and Michigan from 99 hospitals using GWTG-Stroke from July 2014 through December 2015. Stroke subsets, GWTG award status, and ALOS were examined.

Results:
The national ALOS is 5.22 days for ischemic stroke, 12.75 days for subarachnoid hemorrhage (SAH), and 8.5 days for intracerebral hemorrhage (ICH). The ALOS for ischemic stroke was 4.36 days for non-award winning hospitals and 4.52 days for award winning hospitals. The ALOS for SAH was 7.51 days for non-award winning hospitals and 10.77 days for award winning hospitals. The ALOS for ICH was 18.63 days for non-award winning hospitals and 6.80 days for award winning hospitals. Further broken down, hospitals with a higher award (gold vs silver), had longer ALOS for both SAH and ICH (11.11 vs 8.72 and 7.07 vs 5.84 respectively), while there was no significant difference in ALOS for ischemic stroke.

Conclusions:
This study demonstrated that GWTG-Stroke award winning hospitals have a shorter ALOS for ICH and a higher ALOS for SAH than non-award winning hospitals. Those hospitals that have attained gold award status more closely align with national ALOS. Thus, hospitals that are more adherent to guideline recommended care via a quality improvement program may be more efficient when providing care, which impacts hospitals costs.
Abstract 249: Dose-response Relationship Between the Risk of Vasovagal Syncope and Body Mass Index
Authors: Yamada Tomohide , Yanagimoto Shintaro
Published: June 2021

Vasovagal syncope (VVS) is the most common type of syncope with associated fatigue, nausea, abdominal discomfort, and dizziness. VVS usually resolves uneventfully, but sometimes leads to head trauma or other injuries. Blood tests are the most commonly performed medical tests, and prevention of VVS associated with blood sample collection is important from a medical or public health perspective.

We investigated the association between body mass index (BMI), systolic blood pressure (SBP), estimated circulating blood volume (CBV), and the risk of VVS in healthy young adults undergoing blood tests, and attempted to quantify potential dose-response relations and identify high-risk populations.

We examined 18,888 students entering the University of Tokyo between 2011 and 2016, who had a normal electrocardiogram, no structural heart disease, and no previous syncopal loss of consciousness. VVS was defined as syncope occurring before, during, or immediately after blood collection, with symptoms including weakness, pallor, cold sweats, nausea, vomiting, a lower systolic blood pressure or pulse rate compared with baseline, and need for assistance from a physician without any sequelae. Occurrence of VVS was confirmed by medical staff. CBV was calculated according to Nadler’s method.

The subjects had a mean age of 19±1 years and 19% (n=3522) were women. Mean BMI, SBP, and CBV were 21.0±2.9 kg/m2, 121±12 mmHg, and 4.4±0.4 L for men, and were 19.8±2.3 kg/m2, 108±11 mmHg, and 3.3±0.3 L for women, respectively.

VVS was diagnosed in 0.63% of the subjects (n=119) (19% women). By dose-response analysis, lower BMI showed a non-linear association with a significantly higher risk of VVS in men (p for non-linearity<0.001). Compared with a BMI of 22 kg/m2, the risk of VVS increased markedly at a BMI of 20 (OR 1.52; 95%CI 1.02-2.27) and increased further at a BMI of 18.5 (2.35; 1.41-3.92). Similarly, compared with the median SBP (120 mmHg), lower SBP showed a non-linear association with a higher risk of VVS (110 mmHg: OR 1.46, 95%CI 1.11-1.91; 100 mmHg: 2.51, 1.57-4.02; and 90 mmHg: 4.41, 1.91-10.2) (p for non-linearity=0.04). There was a negative linear correlation between CBV and VVS (P for non-linearity=0.43) in men. Lower CBV was associated with a higher risk of VVS. However, there were no significant correlations of these parameters in women. Also, there were no significant association between VVS risk and other covariates.

We demonstrated that lower BMI and SBP showed a J-curve association with the risk of VVS in men. Low BMI, SBP, and CBV are useful predictors for primary prevention of VVS. Providing advice on preventive methods such as counter-pressure maneuvers might be beneficial for high-risk persons, especially those who are “underweight” or have “hypotension”.
Abstract 251: Long-term Outcomes and Implantable Cardioverter Defibrillator Use in Peripartum Cardiomyopathy
Authors: Mahowald Madeline , Basu Nivedita , Kawamoto Kris , Davis Melinda
Published: June 2021

Background:
Many studies of outcomes in peripartum cardiomyopathy (PPCM) are limited by short-term follow-up of 6-12 months. Long-term mortality rates and outcomes are largely unknown. Prior research has also suggested under-utilization of implantable-cardioverter defibrillators (ICD) in this population.

Methods:
Patients with PPCM at a tertiary care center were retrospectively identified using ICD9 code 674.5x from 2000-2011, and each chart was manually reviewed. Clinical, demographic, and echocardiographic data were reviewed, with follow-up through November 2016. Recovery was defined as ejection fraction (EF) >= 55%.

Results:
Of 60 patients, 35 were white (58.3%) and 16 were black (26.7%). Mean age at diagnosis was 29.6 years (range 18-44 years) and average follow-up was 5.8 years. Mean EF at time of diagnosis was 20.2 +/- 4%, at 6-months follow-up it was 39.6 +/- 4%, and at final follow-up was 38.7 +/- 3%. Recovery (EF>=55%) occurred in 38%. Of those who did not recover (62%), the final mean EF was 25%. ICD was placed in 19 patients (51%). Only one patient with an ICD later recovered at one year follow-up. LVAD or transplant occurred in 8 patients, and death occurred in 7 patients with a mean survival of 4.4 +/- 1.4 years. Five patients experienced subsequent deterioration in their EF (with a range of 10-35%) in the absence of a subsequent pregnancy, with a mean decrease in EF of 23.2%. Three of these patients had achieved full recovery (EF>=55%) prior to subsequent decline.

Conclusions:
Patients with PPCM who have initial improvement in EF or even full recovery, can later suffer deterioration, even in the absence of subsequent pregnancy. This finding warrants continued surveillance and raises the question whether lifelong medical therapy may be indicated despite recovery. This study also shows a higher rate of ICD utilization than prior reports.
Abstract 253: Out of Range INR Results Lead to Increased Health Care Utilization in Four Large Anticoagulation Clinics
Authors: Barnes Geoffrey D , Gu Xiaokui , Kline-Rogers Eva , Graves Chris , Puroll Eric , Townsend Kevin , McMahon Ellen , Craig Terri , Froehlich James B
Published: June 2021

Background:
The impact on healthcare utilization of a single out of range (OOR) INR value not associated with any bleeding or thromboembolic complication among chronic warfarin-treated patients is not well described.

Methods:
At four large phone-based anticoagulation clinics in Michigan, warfarin-treated patients with atrial fibrillation (AF) or venous thromboembolism (VTE) were identified and data collected via medical chart abstraction. Propensity score matching was used to identify two groups closely matched on patient characteristics: the OOR INR group (INR value < 1.8 or > 3.2 if target range was 2-3) and the control group (INR value between 1.8 and 3.2). Data for each anticoagulation clinic interaction and INR lab test were abstracted until the patient had 2 subsequent and sequential in-range INR values. Methods and frequency of interactions between the anticoagulation clinic and patient were recorded, described as median and interquartile ranges (IQR) and compared using Poisson regression with adjusted means.

Results:
Demographics were similar for the 116 OOR INR patients and the 58 control patients studied (mean±SD age 72.1±13.0 and 74.3±11.3 years, respectively). Indications for warfarin were more commonly venous thromboembolism in the OOR versus in-range patients (42.2% vs. 27.6%, p=0.06). OOR and in-range INR patients experienced a median of 3 (IQR 3-5) and 3 (IQR 3-3) with adjusted means of 4.2 and 3.2 (p<0.001) INR lab draws until two sequential tests were in-range. OOR INR patients required a median 5 (IQR 3-6) with adjusted means of 5.3 and 3.7 interactions with the anticoagulation clinic versus 3 (IQR 3-4) for in-range INR patients (p<0.001). OOR INR patients more often required phone calls (adjusted means 2.9 versus 0.9, p<0.001) but fewer mailed letters (adjusted means 1.3 versus 2.3, p<0.001) than in-range INR patients. OOR INR patients more often required multiple types of contact than in-range INR patients (83.6% versus 55.2%, p<0.001). Contact was most frequently performed by registered nurses (adjusted means 3.4 versus 2.9, p=0.059) and administrative assistants (adjusted means 1.3 versus 0.5, p<0.001) for both OOR and in-range INR patients. Blood count and renal function lab test were similarly rare for both groups (mean 0.4, median 0, p=0.74 for each).

Conclusions:
Warfarin-treated patients who experience OOR INR values without any bleeding or thromboembolic complication require more frequent interactions with the anticoagulation clinic, including more telephone calls and multiple types of contact.
Abstract 254: Persistent SES Disparities in Cardiovascular Risk Factors and Health in the United States: MEPS 2002-2013
Authors: Valero-Elizondo Javier , Spatz Erica S , Salami Joseph A , Osondu Chukwuemeka U , Desai Nihar R , Rana Jamal S , Virani Salim S , Blankstein Ron , Blaha Michael J , Veledar Emir , Nasir Khurram
Published: June 2021

Background:
Given the health and cost burden of cardiovascular (CV) disease, we aimed to describe the trends in CV risk factors (CRF) in the US over the last twelve years, and quantify the disparities in healthcare by socioeconomic status (SES).

Methods:
The 2002-2013 Medical Expenditure Panel Survey (MEPS), a nationally representative sample was the basis for our study. CRFs (hypertension, diabetes mellitus, hypercholesterolemia, smoking, lack of physical activity and obesity) were identified by ICD9CM codes and/or self-report. Individuals were stratified by income level (per the federal poverty level), and proportions and logistic regression models were used to study trends and relationships for each CRF in two-year intervals. All analyses took into consideration the survey’s complex design. Inclusion criteria: age ≥ 18, BMI ≥ 18.5 and a positive sampling weight.

Results:
The study sample consisted of 250,371 MEPS participants (46 ± 14 years of age, 49% male), translating into 1.3 billion US adults. During the study period, the proportion of individuals with obesity increased overall, though moreso among people of low SES (Table). Trends in diabetes prevalence increased (from 9.6% to 12.8% in “Poor/Near Poor” and 5.6% to 8.3% in “High Income”, both
p trend
< 0.001) and hypertension (from 28.5% to 36.3% in “Poor/Near Poor” and 24.2% to 33.4% in “High Income”, both
p trend
< 0.001), though the greatest relative change was observed among the Middle/High Income SES group. Prevalence of inadequate physical activity increased in all SES categories, with the “Poor/Near Poor” group having the most drastic change (32.4% vs. 55.4%,
p trend
< 0.001), and a relative percent change of 71.1% increase in this category. Smoking declined across time in all SES categories, and hypercholesterolemia showed no significant changes. In pooled analysis, the odds of having a “Poor CRF Profile” (≥ 4 CRFs) for “Poor/Near Poor” SES were 36% higher when compared to “High Income” SES (OR 1.36, 95% CI [1.30, 1.44]) (Table).

Conclusion:
Disparities in the prevalence of CRFs have increased over the past 12 years, and have worsened for some conditions, including obesity, diabetes, hypertension and physical inactivity. There is a need for healthcare initiatives and policies to target the groups most in need.
Abstract 260: A Qualitative Study of Patient-reported Challenges to Heart Failure Home Management
Authors: Sevilla-Cazes Jonathan , Bowles Kathryn H , Ahmed Faraz S , Gallagher Tom , Kangovi Shreya , Goldberg Lee R , Alexander Lynn , Jaskowiak Anne , Barg Frances K , Kimmel Stephen E
Published: June 2021

Background:
Patients with heart failure (HF) have high 30-day hospital readmission rates. Interventions designed to prevent readmissions have had mixed success. Viewing HF home management through the lens of a patient’s experience may reframe the readmission “problem” and inform a range of alternative strategies.

Methods:
We conducted open-ended, semi-structured interviews with HF patients who had a 30-day readmission or had been discharged in the past month. Data were analyzed using a grounded theory approach. The purpose of the interviews was to understand the challenges to home HF management and the perceived reasons for readmission.

Results:
Face-to-face interviews with 31 patients, 16 (52%) with a 30-day readmission, revealed a combination of physical and socio-emotional influences on patients’ home management. Major themes related to readmission included symptom management, adherence vs adaptation, and emotional reactions. While patients reported symptom management as the leading reason for readmission, addressing symptoms was more complex than following recommendations. Patients identified an uncertainty regarding recommendations, caused by unclear instructions and temporal incongruence between behavior and symptom onset, as a factor that impaired their competence in making routine management decisions and resulted in a cycle of limit testing. Patients reported adapting —rather than strictly adhering to— recommendations to accommodate their emotional needs, socio-economic constraints, and comorbidities. For some, the onset of a distressing constellation of symptoms led to a cycle of despair characterized by fear and hopelessness, with the hospital being viewed as the safest place for recovery (see Figure 1).

Conclusion:
Anticipatory guidance regarding challenges to adherence may reduce uncertainty, but is likely insufficient. Early palliative care referral may help mitigate distressing symptoms, and address extreme emotions, perhaps forestalling premature readmission.
Abstract 003: Direct and Indirect Effects of Prostaglandin E
2
and Its EP1/EP3 Receptors on Dendritic Cell Activation in Mice with L-NAME/High Salt-induced Hypertension
Authors: Xiao Liang , Itani Hana A , Kraemer Maria P , Breyer Richard M , Harrison David G
Published: June 2021

We recently identified a pathway underlying immune activation in hypertension. Proteins oxidatively modified by reactive γ-ketoaldehydes (isoketals) accumulate in dendritic cells (DCs). These are immunogenic and lead to subsequent T lymphocytes activation. The local signals that stimulate DCs to accumulate isoketal adducts remain undefined. Prostaglandin E
2
(PGE
2
) has been implicated in the inflammation associated with hypertension. We hypothesized that PGE
2
via its EP3 receptor contributes to DC activation in hypertension. EP3
-/-
mice and wild type (WT) littermates were exposed to sequential hypertensive stimuli involving an initial 2-week exposure to the NOS inhibitor L-NAME (LN) in drinking water, a 2 week washout period, and a subsequent 4% high salt diet (HS) for 3 weeks. In WT mice, this protocol increased systolic pressure from 123±2 to 148±8 mmHg (p<0.05), and renal CD4
+
and CD8
+
effector memory T cells by 2 to 3 fold. This was associated with a striking accumulation of isoketal protein adducts in splenic DCs. However, the increases in blood pressure, renal T cell infiltration and DC isoketal formation were completely prevented in EP3
-/-
mice. We further hypothesized that EP3 receptors contribute to oxidative stress production in the kidney. As measured by dihydroethidium with confocal microscopy, the LNHS protocol induced marked increases in superoxide production in WT mice, but not in EP3
-/-
mice. To examine the direct effects of PGE
2
, splenic DCs were incubated with PGE
2
in vitro for 24 hours. PGE
2
dose-dependently increased isoketal-adduct formation in DCs (vehicle: 8.8±5.1% vs. 50 nM PGE
2
: 41.4±11.7%, p<0.05). Interestingly, this effect was not blocked by the EP3 receptor antagonist DG-041 (30 nM), but was completely prevented by the EP1 receptor blocker SC-51322 (20 μM). These data indicate both direct and indirect roles of PGE
2
in DC activation in hypertension. In vivo, PGE
2
has a predominant effect on EP3 receptors to enhance renal vascular ROS production, which likely leads to isoketal-adduct formation and accumulation in DCs. PGE
2
also acts directly on DCs via its EP1 receptors to stimulate intracellular isoketal formation. Together, these findings provide additional information as to how PGE
2
modulates inflammation in hypertension.
Abstract 008: Depletion of Antibody-Secreting Plasma Cells Attenuates Hypertension in an Experimental Model of Autoimmune Disease
Authors: Taylor Erin B , Ryan Michael J
Published: June 2021

Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder that is characterized by aberrant immunoglobulin (Ig) production, notably pathogenic autoantibodies, and is associated with prevalent hypertension, renal injury, and cardiovascular disease. Recent studies by our laboratory have shown that chronic B cell depletion with anti-CD20 monoclonal antibody reduces autoantibody production and prevents the development of hypertension in an experimental female mouse model of SLE (NZBWF1). However, the treatment was only effective when administered before the onset of autoantibody production. Because long-lived plasma cells produce the majority of serum Ig and are the primary source of autoantibodies in SLE, we hypothesized that depletion of plasma cells using the proteasome inhibitor bortezomib would lower autoantibody production and attenuate hypertension. Thirty week old female NZBWF1 and control (NZW) mice were injected i.v. with vehicle (0.9% saline) or bortezomib (0.75 mg/kg) twice weekly for four weeks. Percentages of CD138
+
intracellular-κ light chain
+
plasma cells in the bone marrow were lower in bortezomib treated SLE mice compared to vehicle-treated SLE mice (1.7±0.19% vs. 0.95±0.18%, p<0.05), as assessed by flow cytometry. Total plasma IgG was higher in SLE mice as compared to control mice (5.02±1.2 mg/mL vs. 2.88±0.78, p<0.05), and were lower in SLE mice treated with bortezomib (1.5±0.5 mg/mL, p<0.05 vs. SLE-vehicle). In addition, bortezomib treatment reduced circulating anti-dsDNA IgG levels in SLE mice (OD450 1.36±0.25 vs. 0.44±0.11 p<0.01). Urinary albumin excretion, an indicator of glomerular injury, was increased in SLE mice as compared to control mice (16.8±10.1 vs. 0.015±0.002 mg/day, p<0.05) and was lower in SLE mice treated with bortezomib (0.24±00.16 mg/day, p<0.05 vs. SLE-vehicle). Mean arterial pressure (MAP; mmHg) measured in conscious mice by carotid artery catheter was higher in SLE mice than in control mice (142±5 vs. 118±3, p<0.001). MAP was significantly lower in SLE mice treated with bortezomib when compared to vehicle treated mice (119±4 vs. 142±5, p<0.001). These data suggest that production of autoantibodies by plasma cells in SLE mechanistically contribute to the pathogenesis of hypertension.
Abstract 011: An Orally Absorbable Potent NHE3 Inhibitor Attenuates Angiotensin II-induced Hypertension Primarily by Inhibiting NHE3 in the Proximal Tubule of the Kidney
Authors: Li Xiao C , Nguyen Hoang , Zhuo Jia L
Published: June 2021

We have recently shown that angiotensin (ANG II)-induced hypertension was attenuated in mice with global (

Nhe3
-/-

) and

Nhe3
-/-

mice with transgenic rescue of the NHE3 gene selectively in small intestines (tg

Nhe3
-/-

), suggesting an important role of NHE3 in the development of ANG II-dependent hypertension. In this study, we specifically tested whether the pharmacological inhibition of NHE3 mainly in the proximal tubules of the kidney attenuates ANG II-dependent hypertension induced by a low and slow pressor dose of ANG II supplemented with a high salt diet. Overall, 9 groups (n=5-12) of adult male C57BL/6J mice were infused with or without ANG II (500 μg/kg/day, i.p. via minipump) and supplemented with or without a 2% NaCl diet to slowly and moderately increase systolic blood pressure (SBP) in 2 weeks. ANG II alone increased SBP from 116 ± 2 mmHg to 140 ± 2 mmHg (
p
<0.01), and supplement of ANG II with a 2% NaCl diet further increased SBP to 147 ± 4 mmHg (
p
<0.05). Concurrent treatment with an orally active, absorbable NHE3 inhibitor AVE0657 (Sanofi-Aventis; 20 mg/kg/day, p.o.) significantly decreased SBP to 125 ± 4 mmHg in ANG II-infused mice (
p
<0.01), and to 134 ± 6 mmHg in ANG II-infused mice supplemented with 2% NaCl (
p
<0.01), respectively. Further treatment with AVE0657 and losartan, an AT
1
receptor blocker (20 mg/kg/day, p.o.), completely normalize SBP in mice treated with ANG II and 2% NaCl to control (115 ± 5 mmHg,
p
<0.01). In the kidney, AVE0657 significantly increased 24h urinary Na
+
excretion from 157.1 ± 6.7 to 207.7 ± 8.1 μmol/24h (
p
<0.01) without altering 24h urine excretion or SBP. Furthermore, AVE0657 did not significantly alter 24 h fecal Na
+
excretion in non ANG II-infused (4.99 ± 0.37 μmol/24h, n.s.) or ANG II-infused mice (4.19 ± 0.67 μmol/24h, n.s.), compared with control (4.02 ± 0.20 μmol/24h,
n.s.
) or global

Nhe3
-/-

mice (50.8 ± 0.8 μmol/24h,
p
<0.01). Since small intestines in the gut and the proximal tubules of the kidney express the vast majority of NHE3 in the body, these results provide preclinical evidence and perspectives that orally absorbable NHE3 inhibitors may be pharmacologically beneficial to prevent and treat hypertension induced by ANG II and a high salt, mainly by inhibiting NHE3 in the proximal tubule of the kidney.
Abstract 012: Involvement of Drp1, A Mitochondrial Fission Inducer, in Angiotensin Ii-induced Hypertensive Vascular Remodeling in vitro and in vivo
Authors: Kawai Tatsuo , Forrester Steven J , Elliot Katherine J , Eguchi Kunie , Rizzo Victor , Eguchi Satoru
Published: June 2021

Mitochondrial dysfunction has been implicated in various types of cardiovascular diseases which may involve overload and de-compensation in mitochondrial quality/quantity control. However, limited mechanistic insight is available regarding the contribution and mechanism of mitochondrial quality control in hypertension. In the present study, we tested our hypothesis that enhancement of mitochondrial fission via Drp1 activation in vascular smooth muscle cells (VSMCs) is involved in hypertensive vascular remodeling. Rat aortic VSMCs pretreated with adenovirus encoding Drp1 siRNA (Ad-siDrp1) or control non-silencing RNA (100 moi) were stimulated with 100 nM angiotensin II (AngII) up to 72 h. 8 week old male C57/BL6 mice were infused with (1000 ng/kg/min) for 2 weeks with or without treatment of Drp1 inhibitor mdivi1 (25 mg/kg ip every other day). In VSMCs, AngII induced transient mitochondrial fission (max at 2-4 h assessed by mito-tracker staining) associated with Drp1 phosphorylation at Ser616 (10-30 min). Pretreatment of ad-siDrp1 (100 moi) or mdivi1 (5 μM) attenuated AngII-induced mitochondrial fission. Ad-siDrp1 or mdivi1 also attenuated AngII-induced enhancements of mitochondrial reactive oxygen species (ROS) generation, total cell protein, cell volume and extracellular collagen content. In mice, mdivi1 significantly suppressed vascular hypertrophy and perivascular fibrosis induced by AngII in aorta, heart and kidney. mdivi1 also inhibited AngII-induced left ventricular hypertrophy assessed by heart weight body weight ratio (mg/g: 7.8±0.9 vs 6.3±0.2 p<0.01) as well as by echocardiogram. However, mdivi1 did not affect hypertension induced by AngII assessed by telemetry (mean arterial pressure: sham 150±8 vs mdivi1 155±7 mmHg). KDEL and nitro-tyrosine staining of the heart and kidney suggest attenuation of vascular ER stress and oxidative stress, respectively. In conclusion, this data suggests that Drp1-dependent mitochondrial fission contributes to AngII-induced cardiovascular remodeling independently of hypertension via enhancement of mitochondrial ROS and ER stress in target organs.
Abstract 017: Optogenetic Activation of OVLT Neurons Stimulates Water Intake and Produces a Sympathetically-Mediated Increase in Arterial Blood Pressure
Authors: Stocker Sean D , Simmonds Sarah S
Published: June 2021

The organum vasculosum of the lamina terminalis (OVLT) plays a pivotal role in body fluid homeostasis and arterial blood pressure (ABP) regulation. The OVLT lacks a complete blood-brain-barrier and responds to an array of circulating factors such as NaCl and angiotensin II. Lesion of the anteroventral third ventricular region which includes the OVLT attenuates or reverses several forms of salt-sensitive hypertension. However, there is limited evidence to demonstrate that direct activation of OVLT neurons alters body fluid homeostasis or elevates ABP. To address this question, Male-Sprague-Dawley rats (300-350 g) received an injection of rAAV9-CamKII-hChR2(H134R)-EYFP (10
12
particles/mL, 200nL) into the OVLT. A fiber optic cannula (200μm) was implanted 300μm dorsal to OVLT. Approximately 2-3 week later, optogenetic activation of OVLT neurons (10ms pulse, 50% duty cycle, 30 min) produced frequency-dependent increases in water intake (1Hz: 1.0±0.5mL; 5Hz: 4.2±0.6mL; 10Hz: 8.0±1.8; 20Hz: 10.2±2.1mL, n=4, P<0.05). In separate experiments, optogenetic activation of OVLT neurons produced a frequency-dependent increase in mean ABP (1Hz: 1±1 mmHg; 5Hz: 3±1mmHg; 10Hz: 7±1mmHg; 20Hz: 13±1mmHg, n=4, P<0.05) and heart rate (1Hz: 3±6 bpm; 5Hz: 15±5bpm; 10Hz: 40±12 bpm; 20Hz: 62±14bpm, n=4, P<0.05). Pretreatment with the vasopressin antagonist Manning Compound (10ug/kg, IV) did not affect these responses. However, pretreatment with the ganglionic blocker chlorisondamine (5mg/kg, IV) abolished the pressor (20Hz: 1±1 mmHg, P<0.01) and tachycardic (20Hz: 4±7 bpm, P<0.05) responses to activation of OVLT neurons. Finally, in vivo single-unit recordings demonstrate that optogenetic activation produced frequency-dependent increases in cell discharge of OVLT neurons responsive to either intracarotid injection of hypertonic NaCl (0.3M NaCl, 50μL over 10 s, n=6) or angiotensin II (100ng over 10s, n=3). Collectively, these data provide evidence that direct activation of OVLT neurons stimulates thirst and produces a sympathetically-mediated increase in ABP.