bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 18347: Patterns of Physical Activity and Survival Following CRT-D Implantation: The ALTITUDE Activity Study
Authors: Kramer Daniel , Jones Paul W , Rogers Tyson , Mitchell Susan L , Reynolds Matthew R
Published: March 2022

Background:
Device-detected physical activity predicts survival following ICD implantation. CRT is implanted in part to improve the functional status of patients with CHF. Patterns of activity changes following CRT implantation, and their relationship to survival, have not been described.

Methods:
CRT-D patients in the Boston Scientific ALTITUDE registry from 2008-2012 with activity measurements through 210 days were eligible. Remote monitoring data were used to calculate physical activity differences (mean minutes/day) between baseline post-implant (first 3-10d); short-term (30-60 days) and 6 months (180-210 days). The relationship between activity changes between baseline and 6 months by quintile and survival were modeled using Cox regression.

Results:
Among 36,699 patients (mean age 70.8 + 10.9, 29.5% women), mean activity was 68.9 + 48.9 min/day at baseline, 97.9+ 60.7 min/day at 30-60 days, and 100.0+ 64.9 min/day at 6 months. Mean paired differences between baseline and 6 month activity was 31.1 min/day (95% CI, 30.6-31.6, P<0.0001). However, mean paired differences between 30-60 days and 6 months was only 2.2 min/day (95% CI 1.8-2.5, P<0.0001). Unadjusted survival from 6-months post-CRT-D implant in the highest vs lowest quintile of activity change (baseline - 6 months) was 96.8% vs 83.9% at 1 year, and 87.6% vs 62.1% at 3 years (log-rank P <0.0001 for both comparisons). After adjustment for age, gender, and baseline activity, change in activity at 6 months strongly predicted survival (HR 1.51 per 30 min change, 95% CI 1.48-1.55, two-sided Wald test P <0.0001).

Conclusion:
This large, nationwide sample of CRT-D recipients suggests that physical activity following implantation increases an average of over 30 min/day, with most of the change manifest in the 2nd month of therapy. Adjusted survival is markedly improved in patients who demonstrate improved activity levels.
Abstract 18348: ATF6 and the Adaptive ER Stress Response Promotes Proliferation and Viability of Mouse Cardiac Progenitor Cells
Authors: Stauffer Winston T , Doroudgar Shirin , Stephens Haley N , Bailey Brandi , Glembotski Christopher C
Published: March 2022

C-kit+ cardiac stem cells, herein called cardiac progenitor cells (CPCs), are beneficial when administered to infarcted mouse hearts. Though the mechanism of these benefits is unknown, CPC vitality likely plays a major role. Thus, investigating the factors governing CPC survival in the ischemic heart may lead to more effective therapeutic strategies. Our previous studies showed that misfolded proteins accumulate in the sarco/endoplasmic reticulum (SR/ER) of the ischemic heart, and that SR/ER protein quality control, which includes the adaptive ER stress response, is critical for the synthesis of most secreted proteins, receptors, and contractile calcium-handling proteins. The transcription factor, ATF6, is a key component of the adaptive ER stress response because it induces genes that reduce the accumulation of misfolded proteins, improving myocyte survival during ischemic stress. While our lab has shown that, in cardiac myocytes, ATF6 is cardioprotective in the ischemic heart, neither the ER stress response nor ATF6 have been examined in CPCs. Accordingly, the hypothesis of this study is that ATF6 and the adaptive ER stress response are critical for optimal survival of CPCs. To address this hypothesis we compared the viabilities of mouse CPCs to neonatal rat ventricular myocytes (NRVM) subjected to treatments that mimic ischemic ER stress in the heart. We found that, compared to NRVM, CPCs exhibited lower levels of adaptive ER stress response gene expression and increased cell death in response to ER stress. Thus, relative to NRVM, the adaptive ER stress response is not fully developed in CPCs. We also found that either siRNA-mediated knock down of ATF6 or chemical inhibition of ATF6 activation with AEBSF decreased adaptive ER stress response gene expression; therefore, ATF6 is an essential component of the adaptive ER stress response in CPCs. Strikingly, ATF6 knockdown decreased CPC viability and proliferation by as much as 70%. Thus, compared to cardiac myocytes, CPCs exhibit a reduced adaptive ER stress response and are more sensitive to ER stress, suggesting that enhancement of the ATF6-mediated adaptive ER stress response in CPCs may be a viable therapeutic approach for enhancing stem cell-mediated myocardial repair.
Abstract 18361: Lipidomic Profiles are Associated With Incident Coronary Heart Disease in Women
Authors: Rexrode Kathryn M , Balasubramanian Raji , Paynter Nina , Gopal Shuba , Guilianini Franco , Allison Matthew , Eaton Charles B , Martin Lisa W , Howard Barbara V , Tinker Lesley , Manson JoAnn E , Cook Nancy , Albert Christine A , Clish Clary
Published: March 2022

Background:
Advances in lipidomics allow profiling of hundreds of lipid compounds, but prior studies have been limited by relatively small case numbers and scant data in women.

Methods:
Four hundred confirmed, incident cases of MI and fatal CHD in the Women’s Health Initiative (WHI-OS) were frequency matched to 400 controls by age, race, hysterectomy, and time-period (mean age 62.7 years; no hormone use). Lipidomic analysis of 196 lipid species from 13 different lipid classes including cholesterol esters (CE), diacylglycerols (DAG),and triacylglycerols [TAG) was performed by liquid chromatography mass spectroscopy. Two independent modeling approaches were used: 1) Individual lipids were studied in logistic regression models and a false-discovery rate (FDR) correction was used to adjust for multiple comparisons (FDR corrected p-value of < 0.05); 2) Lipids were simultaneously considered using a least absolute shrinkage and selection operator (LASSO) algorithm. Metabolites selected by both approaches were included in combined multivariable logistic regression models.

Results:
In multivariable-adjusted logistic models, 17 lipid metabolites were individually and significantly associated with CHD controlling for multiple comparisons, while in mutually adjusted LASSO regression, 8 lipids were significantly associated with CHD. Five lipids were associated with CHD by both methods (Table). When modeled together, only C18.1 CE and C34.3 DAG were associated with risk in fully adjusted models. Results will be validated in separate replication dataset of women from the WHI (396 cases/ 396 controls; to be presented).

Conclusions:
Three long chain highly unsaturated triacylglycerols and one diacylglycerol were associated with decreased risk, while a short chain monounsaturated lipid CE (18.1) was associated with increased risk of CHD in women. Lipidomics may offer insights into biological mechanisms of CHD as well as identify potential markers of risk.
Abstract 18364: Barriers to Community CPR Training in High-risk Neighborhoods- Lessons Learned From the Hands-only CPR Program
Authors: Panchal Ashish R , Del Rios Marina , Waxler Jennifer , Heard Debra , Sasson Comilla
Published: March 2022

Background:
Improving the performance of bystander CPR in high-risk communities is essential for decreasing disparities in cardiac arrest survival. In this study, we identified the barriers to community CPR training in high-risk neighborhoods as part of the multi-centered trial of the Hands-Only™ CPR Program - a novel intervention targeting neighborhoods with high incidence of cardiac arrest and low bystander CPR rates.

Methods:
The Hands-Only CPR program was implemented in high-risk neighborhoods in Tampa, FL, Columbus, OH and Chicago, IL. Participants underwent group-based Hands-Only CPR training (1 hour) with a CPR Anytime kit, which includes a DVD and manikin. A $10 gift card incentive was offered to participants who used the kits to train family and friends and returned data at 2 weeks. Study coordinators identified barriers and facilitators to recruitment, training and follow-up.

Results:
In 20 weeks, 815 participants were recruited (Tampa, n=580; Columbus, n=165; Chicago, n=70). Participant demographics differed by site. Participants in Columbus and Chicago were predominantly Black (81% and 88%, respectively) whereas in Tampa they were White (42%) and Hispanic (38%). Annual income was < $30,000 for 45% of participants. Recruitment was challenging even with participants receiving a $10 incentive, CPR Anytime kit, and meal with training. This may be related to CPR training being a low priority compared to other needs (i.e work, child care, neighborhood safety). Communication challenges with the community was cited as another barrier leading to low return response rate of 11%. Highest response rates occurred in Columbus (33%) where community liaisons lived in the neighborhood and interacted with residents daily. Participants did feel comfortable training others using the CPR Anytime kits (P<0.001) The average number of family and friends trained was 4.1 (range: 1 to 15) individuals per respondent.

Conclusion:
The Hands-Only CPR program facilitates training in high-risk neighborhoods and minority populations through a train the trainer model. The biggest challenges faced by the sites were recruiting participants and response rates on family and friends trained. Future research will need to assess methods to improve outreach to this population.
Abstract 18373: Electrocardiographic Intrinsicoid Deflection and Incident Congestive Heart Failure: The Multi-ethnic Study of Atherosclerosis (MESA)
Authors: O'Neal Wesley T , Qureshi Waqas T , Nazarian Saman , Kawel-Boehm Nadine , Bluemke David A , Lima Joao A , Soliman Elsayed Z
Published: March 2022

Introduction:
Intrinsicoid deflection (ID), the time to R wave peak on the electrocardiogram, represents delayed ventricular activation which possibly denotes impaired myocardial function. We hypothesized that delayed ID is predictive of future heart failure events.

Methods:
A total of 6,394 (mean age 62 ± 10; 54% women; 38% whites; 28% blacks; 22% Hispanics; 12% Chinese-Americans) participants without clinically apparent cardiovascular disease or major ventricular conduction delay (QRS ≥120 ms) from the Multi-Ethnic Study of Atherosclerosis (MESA) were included. ID was automatically measured from baseline electrocardiograms (2000-2002) as the maximum ID time in leads V5 and V6. Cox proportional hazards regression was used to compute hazard ratios (HR) and 95% confidence intervals (95%CI) for the association between ID and heart failure.

Results:
Over a median follow-up of 11.2 years, a total of 217 (3.4%) participants developed heart failure (incidence rate per 1000 person-years=3.33, 95%CI=2.91, 3.80). In a multivariable Cox regression analysis adjusted for demographics, cardiovascular risk factors, and potential confounders, each 10 ms increase in maximum ID was associated with an increased risk for heart failure (HR=1.42, 95%CI=1.15, 1.74). The results remained similar when stratified by age, sex, and race/ethnicity.

Conclusions:
Delayed ID is able to identify individuals at risk for developing heart failure before major conduction delays (e.g., bundle branch block) are evident.
Abstract 18385: The Impact of Chronic Kidney Disease on Survival in Patients With Cardiac Resynchronization Therapy
Authors: Daly David D , Maran Arasi , Waring Ashley , Cuoco Frank , Sturdivant Lacy , Leman Robert B , Gold Michael R
Published: March 2022

Introduction:
The prevalence of chronic kidney disease (CKD) is increasing worldwide and it is associated with increased risk of cardiac death. Cardiac resynchronization therapy (CRT) has been shown to increase survival in heart failure patients with left ventricular systolic dysfunction and interventricular conduction delay, but patients with moderate to severe CKD were excluded from the large pivotal randomized trials. Little is known regarding the impact of CKD on survival with CRT long-term.

Hypothesis:
CKD reduced long-term survival among patients with CRT.

Methods:
The follow up of a prospective cohort of 431 consecutive patients undergoing de novo CRT-D implantation from 2002-2010 was performed. The primary endpoint was all cause mortality and was determined using hospital records and the US Social Security Death Index. Glomerular filtration rate was calculated from pre-implant serum creatinine, weight, height, age and race using the Modified Diet in Renal Dysfunction equation. A Kaplan Meier survival analysis was performed grouping patients by CKD stage.

Results:
Patients were followed for up to 12 years with a mean follow up duration of 4.7 ± 3.0 years. The cohort was 72% male with a mean age of 67 ± 11 years, ejection fraction of 25 ± 10 percent and QRS duration of 156 ± 24 msec. The patients with normal renal function and mild CKD (Stages 1 and 2) had improved survival compared with patients with moderate, severe or end stage kidney disease (Stages 3-5). The estimated five year survival was 68.9% for stage 1, 73.5% for stage 2, 55.5% for stage 3 and 45.4% for stage 4/5 CKD with a p<0.001 by log rank test . Multivariate analysis showed that CKD Stage, QRS duration and age were independent predictors of survival with CRT.

Conclusions:
Renal disease is a strong predictor of long term survival with CRT. Moderate to severe CKD is associated with a near 2-fold increased mortality and this should be considered when making decision about the suitability for implantation.
Abstract 18403: In-hospital Evaluation of Low Dose- High Frequency, Case Based Psychomotor Cardiopulmonary Resuscitation Training Demonstrates High Levels of Program Compliance With Good CPR Quality Metrics
Authors: Panchal Ashish R , Norton Gregory , Gibbons Emily , Husa Ruchika , Slattery David E , Kurz Michael C
Published: March 2022

Background:
High quality CPR is critical for survival from cardiac arrest. However, for many providers the opportunity to perform CPR, whether in a training or a clinical situation, is too infrequent to maintain proficiency. Low dose- high frequency case based simulation has been proposed as a method to maintain proficiency for low volume, high-risk medical procedures. We sought to evaluate the feasibility and compliance with a novel low dose- high frequency case based psychomotor cardiopulmonary resuscitation training at a mobile simulation station in an in-hospital setting (Resuscitation Quality Improvement™ (RQI), American Heart Association, Dallas, TX).

Methods:
The RQI system was piloted on two nursing units in a university teaching hospital. The Simulation station was placed in the nursing units with quarterly activities integrated into normal clinical duties. Evaluation of the system focused on staff compliance and evaluation of CPR quality metrics of compression (depth, rate, and release) and ventilations (tidal volume, rate adequacy). Descriptive statistics are presented as means with standard deviations.

Results:
The program was launched in October 2014 with 100 nurses enrolled. Program compliance with last quarter 2014 and first quarter 2015 were 97.1% and 97.2%, respectively. Lack of compliance was due primarily to medical leave exemptions with 1 delinquent participant per quarter. Mean compression depth was 53 ± 3 mm; mean compression rate of 110 ± 9 cpm; percent of adequate compressions of 96 ± 4%; and percent of adequate release of 99 ± 1%. Ventilation data demonstrated mean tidal volumes of 521 ± 69 ml; mean ventilation rates of 11 ± 2 bpm; and percent of adequate ventilations of 85 ± 18%.

Conclusions:
Low dose- high frequency case based psychomotor cardiopulmonary resuscitation training is a feasible method to enhance CPR skill retention in the hospital setting. Program compliance was high through two quarters of training. Performance metrics demonstrate high quality CPR after 2 quarters of exercises indicating CPR skill retention. Further research is necessary to evaluate skill retention over longer periods and the program’s effect on clinical outcome variables.
Abstract 18405: Warfarin Dose Requirements and Polymorphisms in MicroRNA and Nuclear Receptor Genes
Authors: Shahabi Payman , Lamothe Félix , Dumas Stéphanie , Asselin Geraldine , Lemieux Perreault Louis-Philippe , Provost Sylvie , Feroz Zada Yassamin , Perreault Sylvie , Dubé Marie-Pierre
Published: March 2022

Background and Aim:
The marked inter-individual variability in warfarin dose requirement is mainly attributed to the variants of the main target genes across the warfarin pharmacological pathway, i.e. cytochrome P-450 (CYP) 2C9, CYP3A4, ABCB1, vitamin K epoxide reductase complex subunit 1 (VKORC1) and epoxide hydrolase 1 (EPHX1). The expression of these genes is primarily regulated by a complex network of nuclear receptors (NR) which are encoded, in turn, by polymorphic genes. Furthermore, microRNAs (miRNA) can reduce the expression of both warfarin target genes and the genes encoding NRs. We investigated whether the variants of genes encoding i) warfarin targets, ii) NRs involved in the regulation of the targets and iii) miRNA involved in the regulation of NRs and the targets, are associated with warfarin dose requirements.

Methods and Results:
The study was performed using the Quebec Warfarin Cohort consisting of 988 new warfarin users who were recruited over a period of 3 years and were followed-up for 12 months. The candidate genes were selected according to the literature and included 5 warfarin target genes, 9 NRs genes and 29 miRNA genes. SNPs with MAF>0.01 within these genes were selected for the present study from the NCBI database. Genotyping was previously performed using Omni 2.5 array (Illumina, CA) and iPLEX ADME CYP2C9/VKORC1 panel (Agena, CA) and missing SNPs were imputed. We tested the effect of SNPs on the log-transformed values of dose at 3-month post-initiation using multivariate linear regression analysis, and the adjusted significance threshold was set to 2.49 x 10-4. A total of 3970 SNPs, including 702 in target genes, 3162 in NRs and 106 in miRNA genes were studied. For the association with warfarin dose, 137 SNPs in CYP2C9 and VKORC1 were significant, as well as 3 SNPs in nuclear vitamin D receptor (VDR) gene: rs4760658, β = -0,0852, P = 7,32x10-5; rs11168293, β = -0,0809, P = 1,78x10-4; rs4760655, β = -0,0799, P = 2,15x10-4. None of the variants in miRNA genes showed a significant association with warfarin dose.

Conclusions:
Variants in the gene encoding VDR, a nuclear receptor which has been previously shown to be involved in the regulation of CYP2C9, CYP3A4 and ABCB1, may contribute to the variability in response to warfarin.
Abstract 18440: Low Ferritin Levels are Associated With Increased Risk of Heart Failure - The Atherosclerosis Risk in Communities Study
Authors: Silvestre Odilson M , Gonçalves Alexandra , Nadruz Wilson , Claggett Brian , Eckfeldt John H , Pankow James S , Solomon Scott D
Published: March 2022

Introduction:
While severe iron overload has been associated with cardiac damage, iron deficiency is related to worse outcomes in subjects with heart failure (HF).This study investigated the relationship between ferritin, a marker of iron status, and the incidence of HF in a general population based sample.

Methods:
We examined 1,063 participants from the Atherosclerosis Risk in Communities (ARIC) study, mean age 52±5 years, 62% women, free of heart failure, in whom ferritin serum levels were measured at baseline (1987-1989). The participants were categorized in low (200 ng/mL in women and >300 ng/mL in men; n=247) ferritin levels. Multivariable Cox proportional hazards models were used to evaluate the relationship between ferritin and incident HF.

Results:
At 20.9±4.6 years of follow-up, HF occurred in 144 (13.5%) participants. When compared with participants with normal ferritin, those with low level had a higher risk of HF (HR 2.10, 95%CI 1.27-3.47; p=0.004), while there was no significant difference between those with normal and high ferritin levels (HR= 1.07, 95%CI= 0.71-1.63, p=0.7), after adjusting for potential confounders. Low ferritin levels remained associated with incident HF in subjects without anemia (HR= 2.06, 95%CI= 1.18-3.61, p=0.01). (Figure)

Conclusion:
Low ferritin levels are associated with a higher risk of incident HF. These findings suggest that iron deficiency might play a role in the development of HF.
Abstract 18452: Importance of “Dynamic” Rather Than “Static” Central Venous Pressure and Venous Capacitance in Fontan Circulation During Exercise
Authors: Kurishima Clara , Kuwata Seiko , Iwamoto Yoichi , Ishido Hirotaka , Masutani Satoshi , Senzaki Hideaki
Published: March 2022

Background:
High central venous pressure (CVP) is a key driver of developing late complications in patients after Fontan operation. However, we often realize diversity of clinical outcome among patients with similar levels of CVP measured at resting condition during catheterization. We hypothesized that CVP variably increases with exercise and that degree of the increase is associated with clinical outcomes. We also hypothesized that venous capacitance (VC) is an important determinant of the CVP elevation.

Methods:
Dynamic changes in CVP estimated from continuous monitoring of peripheral venous pressure were measured during treadmill exercise (TM) in 21 Fontan patients and 10 age-matched control patients with biventricular (BV) circulation. The VC was calculated during temporal occlusion of inferior vena cava (IVC) at the time of catheterization.

Results:
Fontan patients exhibited significantly shorter duration of exercise with limited increases in heart rate and cardiac output. CVP significantly increased during exercise in both groups, but the degree of CVP elevation was much higher in Fontan patients than in controls (Fontan: from 10.8 to 18.4 mmHg vs. control: from 4.3 to 8.8 mmHg, P<0.05). Importantly, maximum CVP during exercise in Fontan group varied considerably among patients with similar resting CVP, and is significantly and positively correlated with a liver fibrosis marker of type 4 collagen 7S (P <0.01). Furthermore, maximum CVP during exercise in Fontan group negatively correlated with the VC, but not with pulmonary resistance.

Conclusions:
CVP of the Fontan circulation easily rises during exercise in proportion to the reduced VC, and the degree of CVP rise may be a contributor of hepatic complication. These results suggest the importance of assessing dynamic CVP in patients after Fontan operation. The results also suggest potential importance of daily life modification and/or medical treatment to minimize the dynamic changes in CVP to improve the prognosis of Fontan patients. VC may be a viable target for this purpose.
Abstract 18473: Filling a β-blocker in the Week After Discharge for a Heart Failure Hospitalization is Associated With a Lower Risk of Rehospitalization Among Medicare Beneficiaries
Authors: Levitan Emily B , Van Dyke Melissa K , Chen Ligong , Durant Raegan W , Brown Todd M , Safford Monika M , Kilgore Meredith L
Published: March 2022

Introduction:
In clinical trial populations with heart failure (HF) and reduced ejection fraction, there is evidence that the β-blockers metoprolol succinate, carvedilol, and bisoprolol reduce mortality and hospitalizations. The short-term impact of β-blockers among typical hospitalized HF patients with heavy comorbidity burdens is less clear.

Hypothesis:
Filling a β-blocker within 7 days of HF hospitalization is associated with lower rehospitalization risk 8-30 days after discharge.

Methods:
We identified 76,568 HF hospitalizations in the Medicare national 5% sample among beneficiaries with fee-for-service and medication coverage (20,358 with documented systolic dysfunction). Beneficiary characteristics, β-blocker fills, and rehospitalization for HF, cardiovascular disease (CVD), or any cause were assessed through Medicare claims. We used generalized estimating equations to calculate multivariable-adjusted risk ratios for rehospitalization.

Results:
The average age was 76 years, 61% were women, and 19% were black. Comorbidities were common (hypertension 85%, coronary heart disease 70%, chronic kidney disease 65%, chronic obstructive pulmonary disease 57%, diabetes 53%, atrial fibrillation 48%, depression 25%, hypotension 21%, valvular or rheumatic heart disease 15%). Almost all had prior diagnoses of HF (99%). Within 7 days of discharge, 25% filled any β-blocker and 17% filled metoprolol succinate, carvedilol, or bisoprolol. In the 8-30 days following discharge, 9% were rehospitalized for HF, 12% for CVD, and 22% for any cause. Filling a β-blocker was associated with a lower risk rehospitalization for HF, CVD, and any cause in both the overall population and the subgroup with documented systolic dysfunction (
Table
).

Conclusions:
Medicare beneficiaries with HF who filled β-blockers shortly after discharge had better short-term prognosis; however, risk of rehospitalization among those with and without β-blocker fills was high.
Abstract 18476: Myocardial Recovery in Peripartum Cardiomyopathy: Effect of the GNB3 C825T Polymorphism in the Multicenter IPAC study
Authors: Sheppard Richard , Damp Julie , Kealey Angela , Ramani Gautam , Elkayam Uri , Hsich Eileen , Zucker Mark , Alexis Jeffrey , Hanley-Yanez Karen , Pisarcik Jessica , Halder Indrani , McNamara Dennis M ,   for the IPAC Investigators
Published: March 2022

Background:
Peripartum cardiomyopathy (PPCM) remains a major cause of maternal morbidity and mortality. Black race is a risk factor for the disorder and although most women recover myocardial function, previous studies suggest less recovery in black women than in whites. The genetic basis of this racial difference in risk and recovery remains unknown. A polymorphism of a G protein beta subunit (GNB3 C825T) in exon 10 has been studied extensively for a potential role in increased risk of hypertension in blacks. We investigated the impact of the GNB3 C825T polymorphism on myocardial recovery in PPCM in the multicenter IPAC study (Investigation of Pregnancy Associated Cardiomyopathy).

Method:
97 women with new onset of PPCM were enrolled and genotyped for the GNB3 T/C polymorphism. Myocardial function was assessed by echocardiography at study entry, 2, 6 and 12 months postpartum and LVEF calculated at a core lab. Myocardial recovery in subjects with the GNB3TT genotype was compared to subjects with the GNB3 C allele (CC and CT combined) first for the overall cohort then separately in black and white subsets.

Results:
Overall the cohort was 30% black, mean age 30
+
6, and LVEF 0.35
+
0.10 at study entry 31
+
25days post-partum. For the overall cohort, the % GNB3 genotype TT/CT/CC =23/41/36 and differed markedly by Race (Black= 52/38/10 versus Whites=10/43/47, p<0.001). In subjects with the GNB3TT genotype, LVEF was similar early postpartum (TT= 0.35
+
0.07; CT+CC= 0.35
+
0.09, p=0.98) but significantly lower at 2 month (TT=0.38
+
0.15; CT+CC= 0.44
+
0.10, p=0.02), 6 months (TT=0.45
+
0.15; CT+CC= 0.53
+
0.08, p=0.002), and 12 months (TT=0.45
+
0.15; CT+CC= 0.56
+
0.07, p<0.001.). The difference in recovery for GNB3 TT subjects was most pronounced in black women (12 months LVEF for GNB3 TT=0.39
+
0.16; versus CT+CC= 0.53
+
0.09, p=0.02) but was still evident in whites ((TT=0.50
+
0.11; CT+CC= 0.56
+
0.06, p=0.04).

Conclusion:
In IPAC, Women with the GNB3 TT genotype had significantly less myocardial recovery over the first year post-partum, and its impact was particularly evident in black women. The increase prevalence of the GNB3 TT genotype in blacks may contribute to racial differences in myocardial recovery in women with PPCM
Abstract 18478: Balloon Angioplasty of Branch Pulmonary Arteries in Children: A Long Term Outlook
Authors: Ooi Yinn Khurn , Kim Sung In , Gillespie Scott E , Geng Zhi , Kim Dennis W , Vincent Robert N , Christopher Petit J
Published: March 2022

Introduction:
Balloon angioplasty (BA) is widely employed for branch pulmonary artery stenosis (BPAS) in children. Vessel recoil, and hence need for repeat intervention, is common.

Hypothesis:
BA of BPAS has poor long term outcomes.

Methods:
We reviewed our cath database over an 11-year period ending in 2013 and collected data for all pts undergoing BA for BPAS. Primary endpoint was repeat intervention (RI), with other endpoints including acute results, and need for stent or surgical PA plasty (S/S). Central branch pulmonary artery (cPA) was defined as pre-hilum, while peripheral BPA (pPA) was define as post-hilum.

Results:
175 pts underwent 371 BA procedures for BPAS. Primary diagnosis included major aorto-pulmonary collateral arteries (MAPCAs) in 18% (n=32) pts, and single ventricle in 11% (n=20) pts. Median age and weight were 23.6 (9.9 - 65.8) months and 10.7 kg (7.8 - 18.2 kg). Pt follow up was 4.1 (1.1 - 6.5) years. 69% (n=256) of BA was performed on cPA and 31% (n=115) on pPA. Acutely, there was a 14.9% (7.6 - 26.7%) improvement in stenosis in cPA, and 18.5% (9.8 - 28.6%) in pPA (p=0.053). Improvement of pressure gradient was 34.3% (10.4 - 63.4%) in cPA, and 31.6% (0 - 60.7%) in pPA (p=0.324). Higher rates of RI was seen in pPA (55% RI, p=0.035).

For cPA, freedom from RI was 69% at 1 year and 44% at 5 years. Freedom from S/S was 81% at 1 year and 62% at 5 years. Factors associated with higher rate of RI include MAPCAs (65% RI, p=0.039), younger pt age (p=0.042), and lower pt weight (p=0.047). Lower rates of RI were seen in pts with discrete (p=0.007) and severe stenosis (p<0.001). For pPA, freedom from RI was 59% at 1 year and 38% at 5 years. Freedom from S/S was 98% at 1 year and 92% at 5 years.

Conclusions:
Long term outcomes of BA for BPAS are disappointing. BA for BPAS is associated with a high rate of RI with rates exceeding 50% by 5 years. Patients with pre-hilar BPAS and with discrete, severe stenosis appear to respond more favorably. Peripheral BPAS and MAPCAs in particular have a high rate of recurrence.
Abstract 18479: Short- and Long-term Air Pollution Exposure and the Risk for Premature Atrial Contractions and Atrial Fibrillation: The REasons for Geographic And Racial Differences in Stroke (REGARDS) Study
Authors: O'Neal Wesley T , Soliman Elsayed Z , Efird Jimmy T , Judd Suzanne E , Howard Virginia J , Howard George , McClure Leslie A
Published: March 2022

Background:
Air pollution is associated with an increased risk of cardiovascular disease. This suggests a potential association between air pollution and supraventricular arrhythmias, such as premature atrial contractions (PACs) and atrial fibrillation (AF). However, data from large-scale epidemiologic studies supporting this hypothesis are lacking.

Methods:
We examined the association between air pollution with PACs and AF in 28,502 (mean age=65 ± 9.4 years; 55% female; 41% black) participants from the REasons for Geographic and Racial Differences in Stroke (REGARDS) Study. Short-term (2-week) and long-term (1-year) PM2.5 exposure were computed prior to each participants’ baseline visit using individual level geographic information system data at geographic coordinates of participants’ residences. PACs were identified from the baseline electrocardiogram. AF was identified by the study electrocardiogram and by self-reported history of a physician diagnosis. Poisson regression was used to compute relative risk (RR) and 95% confidence intervals (CI) for the association of short- and long-term PM2.5 exposure with PACs and AF, separately.

Results:
A total of 2,356 (9.2%) participants had evidence of PACs and 2,433 (8.5%) had AF at baseline. Short-term PM2.5 (per 10 μg/m3) exposure was not associated with PACs (RR=1.08, 95%CI=0.99, 1.19) or AF (RR=0.92, 95%CI=0.84, 1.02). Increases in long-term PM2.5 per 10 μg/m3 were associated with PACs (RR=1.35, 95%CI=1.10, 1.65) but not AF (RR=0.96, 95%CI=0.79, 1.17).

Conclusion:
Long- but not short-term PM2.5 exposure is associated with PACs. This suggests a potential role for long-term PM2.5 exposure in initiating supraventricular arrhythmias that are triggered by PACs but not maintaining sustained rhythm disorders such as AF.
Abstract 18485: Runx2 Haploinsufficiency Attenuates Angiotensin II-mediated Fibrosis and Proliferation in Mouse Mitral Valves
Authors: Thalji Nassir M , Hagler Michael A , Casaclang-Verzosa Grace , Zhang Bin , Suri Rakesh M , Miller Jordan D
Published: March 2022

We recently reported activation of TGF-β superfamily pathways and activation of Wnt/β-catenin signaling in the pathogenesis of myxomatous mitral valve disease (MMVD), which may converge upon increased Runx2 expression. We also demonstrated that chronic in vivo administration of angiotensin II (AngII) recaptures various molecular aberrations characteristic of human disease -including increased TGF-β signaling and activation of Runx2- in mouse mitral valves. Here, we sought to determine whether Runx2 haploinsufficiency can attenuate molecular and/or phenotypic effects of AngII infusion in mouse mitral valves. We implanted littermate matched Runx2+/+ and Runx2+/- mice with osmotic minipumps delivering AngII (1000ng/kg/min) or saline for 2 weeks. We measured changes in mRNA (qRT-PCR) and protein (immunohistochemistry) levels in mitral valves, and assessed mitral valve function by echocardiography. In Runx2+/+ mice, AngII elicited increased mRNA levels of TGF-β3 and the TGF-β target COL3A1, and increased staining for canonical (p-SMAD2/3) and non-canonical (p-AKT) TGF-β signaling proteins. Runx2 haploinsufficiency attenuated AngII-induced changes in COL3A1 expression and p-AKT staining, without impacting AngII-mediated alterations in TGF-β3 and p-SMAD2/3. Evaluating collagen thickness by picrosirius red staining and visualization under circularly polarized light, AngII infusion in Runx2+/+ mice was associated with increased collagen density at the base of posterior mitral valve leaflets, a change that was abrogated by Runx2 haploinsufficiency. Similarly, Runx2-haploinsufficiency was again protective when examining mRNA and protein levels of the proliferation marker KI67 in response to AngII. Echocardiography identified a trend towards increased mitral valve regurgitation following AngII infusion that was unaltered by Runx2 haploinsuffiency. Collectively, these data suggest that increases in Runx2 expression in the mitral valve may serve to orchestrate tissue fibrosis and cellular proliferation that are hallmarks of MMVD, and that future pharmacological strategies aimed at reducing activity of Runx2 in the mitral valve may yield viable non-surgical alternatives for the management of this condition.
Abstract 18514: Outcomes of Different Mechanical Circulatory Support (MCS) Devices and Transcatheter Aortic Valve Replacement (TAVR): A National Cross-sectional US Experience
Authors: Savani Chirag , Singh Vikas , Patel Samir V , Sonani Rajesh , Arora Shilpkumar , Thakkar Badal , Patel Nilay , Patel Nileshkumar J , Lahewala Sopan , Panaich Sidakpal S , Patel Achint , Bhatt Parth , Patel Aashay , Dave Abhishek , Chothani Ankit , Jhamnani Sunny , Deshmukh Abhishek , Badheka Apurva O
Published: March 2022

Introduction:
The data regarding use of different Mechanical Circulatory Support (MCS) devices in TAVR is limited. The present study was performed to analyze the complications and outcomes of different MCS in TAVR.

Methods:
The subjects under study were obtained from Nationwide Inpatient Sample (NIS) for the years 2011-12 using ICD-9-CM procedure codes for TAVR and MCS. The use of MCS was divided into Intra-aortic balloon pump (IABP), percutaneous ventricular assist devices (PVADs) including Impella and TandemHeart, Extracorporeal membrane oxygenation (ECMO) and percutaneous cardiopulmonary support and cardiopulmonary bypass (CBP) using ICD-9-CM codes. The incidence of in-hospital mortality and occurrence of procedure related complications were analyzed.

Results:
Out of total 1794 TAVR procedures, MCS was utilized in 190 (10.6%) procedures. CBP was the most commonly utilized 136 (71.6%) followed by IABP 36 (18.9%), ECMO 14 (7.4%) and 4 (2.1%). In-hospital mortality was highest with use of IABP (36.6%), followed by ECMO (14.3%), CBP (9.6%) and PVAD (0%) with p-value <0.01. The incidence of complications was similar in IABP and PVAD (100% each) followed by ECMO (85.7%) and CBP (59.4%) with p-value <0.01.

Conclusion:
Being retrospective in design, the present study has no information regarding indications and individual patient related variables in which each of the MCS devices used. Overall, CBP was observed as the most extensive used MCS modality with less mortality (9.6%) and least complications (59.4%).
Abstract 18539: Molecular Imaging of Factor XIII for Early Diagnosis of Coronary Microvascular Disease in Mice
Authors: Zhuang Zhen W , Huang Yan , Ju Rong , Ren Yongming , Hwa John
Published: March 2022

Background:
Coronary microvascular disease (MVD) remains a major clinical challenge, involving endothelial cell (ECs) dysfunction and microthrombosis. We hypothesize that active FXIII can be a specific biomarker for MVD and its activity can be evaluated by a FXIII targeted radiolabeled probe (
99m
Tc-NC100668). We also hypothesize that a murine MVD model can be established through photodynamic therapy (PDT).

Methods:
To optimize the PDT parameters, primary ECs from the heart were isolated and treated with various concentrations of rose bengal, different illumination times, multiple combinations of rose bengal and illumination times (PDT), or nothing to evaluate cell viability and production of reactive oxygen species (ROS). The optimal parameters were translated for
in vivo
MVD model establishment. 52 female mice were assigned to one of four groups: 1) rose bengal, 2) green light, 3) combination, or 4) nothing. Microvascular injury was evaluated by fluorescent myocardial perfusion, coronary microCT angiography, and electron microscopy. To validate the efficacy of this tracer for the diagnosis of coronary MVD, an additional 124 female mice with MVD were injected either 0.1mCi
99m
Tc-NC100668 or
99m
Tc-AH110563 (an inactive analog), at 3 hrs, 24 hrs, 3, 7, or 14 days, for
ex vivo
gamma well counting (GWC, n=100) to assess regional myocardial activity as %injection dose/mg (id/mg), or
in vivo
microSPECT/CT (n=24) to visualize active FXIII.

Results:
PDT were capable of injuring primary ECs by over-producting ROS
in vitro
. Coronary MVD developed only in PDT mice with focal “no flow phenomena”. microCT demonstrated arteriole rarefaction and Electron Microscopy showed luminal microthrombi and loss of endothelial integrity in PDT-treated myocardium. GWC demonstrated
99m
Tc-NC100668 activity within endothelial-damaged myocardium, compared to an inactive tracer at early time points (3 hours: 9.33±1.98 vs. 2.84±1.97% id/mg, p<0.01; 3 days: 3.3±2.23 vs. 0.275±0.072% id/mg, p<0.05).
In vivo
microSPECT/CT images confirmed focal myocardial uptake up to day 3.

Conclusions:
We successfully established a murine model of coronary MVD. Molecular imaging of the activated FXIII allowed visualization of acute and sub-acute coronary micro-thrombi, a hallmark of MVD.
Abstract 18549: High-sensitivity Troponin I in Stable Patients With Atherosclerotic Disease in the TRA2°P- TIMI 50 Trial
Authors: Eisen Alon , Bonaca Marc P , Jarolim Petr , Scirica Benjamin M , Bohula Erin A , Murphy Sabina A , Braunwald Eugene , Morrow David A
Published: March 2022

Background:
Cardiac troponin I, measured with a high-sensitivity assay (hsTnI), is a well-established prognosticator in patients with acute coronary syndromes. However, its prognostic role in patients with stable atherosclerotic disease, particularly with respect to new or recurrent myocardial infarction (MI), is less defined.

Methods:
We measured hsTnI (Abbott ARCHITECT) in 19,429 patients with prior MI, ischemic stroke, or symptomatic peripheral arterial disease, who had available baseline samples in the TRA 2°P-TIMI 50 trial of the platelet inhibitor vorapaxar vs. placebo. hsTnI concentration was categorized into 5 groups based on the detection limit (1.9 ng/L), the 99th percentile reference limit (26 ng/L), and tertiles in between (1.9-26 ng/L). The median follow-up was 2.5 years. Sensitivity analyses excluded patients with a history of MI in the prior 30 days and tested sex-specific cutpoints.

Results:
Higher baseline hsTnI levels were associated with older age, male sex, and an increased burden of atherosclerotic disease. hsTnI identified a graded risk of cardiovascular (CV) death, MI, or stroke with a consistent pattern across each element of this composite, in particular CV death and MI (Figure). This risk relationship was independent of established clinical risk indicators, B-type natriuretic peptide and C-reactive protein (adj-HR 2.17, 95% CI 1.61-2.92 for hsTnI >26 ng/L) and was consistent after excluding pts with recent MI (adj-HR 2.69, 95% CI 1.95-3.71 for hsTnI >26 ng/L). There were no meaningful differences using sex-specific hsTnI cutpoints. The interaction with efficacy of vorapaxar vs. placebo according to hsTnI will be presented.

Conclusion:
When measured in stable patients with established atherosclerosis, hsTnI concentrations, even below the 99th percentile reference limit, effectively stratified the risk of new or recurrent MI.
Abstract 18551: Predisposing Factors of Persistent Symptoms of Depression and Anxiety Among Patients With Acute Coronary Syndrome
Authors: Alhurani Abdullah , Lennie Terry , Moser Debra
Published: March 2022

Introduction:
Depression and anxiety are highly prevalent in patients with acute coronary syndrome (ACS) contributing to poor health outcomes such as mortality and rehospitalization Several studies have also demonstrated a relationship between depression and anxiety and cardiac events in patients with ACS. However, substantial morbidities arise from those patients who persistently suffer from these disorders.

Objective:
The primary objective of this study was to determine the predisposing factors of persistent symptoms of depression and anxiety among patients with ACS.

Methods:
A total of 1199 patients participated from five hospitals in Dublin, Ireland. Logistic regression analyses were used to determine the predisposing factors of persistent symptoms of depression and anxiety. Predisposing factors included age, gender, body mass index, education level, marital status, smoking history, and diabetes history, history of coronary bypass graft (CABG), stroke, or ACS, baseline knowledge, attitudes and beliefs. We also controlled for baseline anxiety when investigating persistent depression and for baseline depression when investigating persistent anxiety. Patients who been depressed or anxious at baseline and three months follow-up were considered to have persistent depression or anxiety.

Results:
Older age (β 0.98; 95% CI: 0.96 - 1.00; p = 0.040), female gender (β 1.99; 95% CI: 1.30 - 3.05; p = 0.002), history of CABG (β 2.10; 95% CI: 1.18 - 3.71; p = 0.011), history of non ST elevation myocardial infarction compared to other ACS (β 1.78; 95% CI: 1.04 - 3.06; p = 0.037), and baseline anxiety (β 1.40; 95% CI: 1.25 - 1.57; p <0.001) were significant predictors of persistent depression. Furthermore, older age (β 0.98; 95% CI: 0.96 - 1.00; p = 0.030), female gender (β 1.98; 95% CI: 1.22 - 3.20; p = 0.005), and baseline depression (β 1.24; 95% CI: 1.14 - 1.36; p <0.001) were significant predictors of persistent anxiety.

Conclusions:
Health care providers need to take in consideration the predisposing factors of persistent depression and anxiety to pre-intervene and prevent morbidities associated with these disorders.
Abstract 18569: Deletion of AT2 Receptor Prevents SHP-1 Expression and Improves Blood Flow in Diabetic Ischemic Hindlimb
Authors: Paquin-Veillette Judith , Guay Andréanne , Geraldes Pedro
Published: March 2022

Introduction:
Ischemia due to narrowing of femoral artery and distal vessels is also a major cause of peripheral arterial disease and morbidity affecting patients with diabetes. We have previously reported that the inhibition of the angiogenic response to PDGF and VEGF in diabetic mice (DM) is associated with the increase expression of SHP-1, a protein that can be activated by the AT2 receptors. It has been shown that the deletion of AT2 receptor in mice promotes angiogenesis within the ischemic muscle, but its role in diabetic condition remains unknown.

Hypothesis:
Our hypothesis is that AT2 receptor induced SHP-1 which contributed to inhibition of pro-angiogenic factor actions in DM mice during ischemia.

Methods:
Non-DM and DM AT2 null mice underwent femoral artery ligation after two months of diabetes. Blood perfusion was measured every week up to 4 weeks post-surgery. Expression of AT1, AT2, angiotensin-converting enzymes (ACE1/2), SHP-1 and angiogenic factors was evaluated.

Results:
Blood flow in the ischemic muscle of DM-AT2KO mice recovered faster and up to 80% four weeks following the surgery, compared to a 51% recovery in DM mice. After four weeks, the expression of pro-angiogenic factors (HIF-1α and VEGF) was diminished in the DM and remained at a basal state in the DM-AT2KO suggesting a faster recovery process in these mice. Interestingly, two weeks after ligation, the expression of VEGF and HIF-1α are elevated in DM-AT2DM compared to DM mice and correlated with a reduction of SHP-1 expression in the ischemic muscles.

Conclusion:
Our results suggest that the deletion of AT2 receptor prevented SHP-1 expression induced by diabetes and restored pro-angiogenic factors causing blood flow reperfusion following ischemia.
Abstract 18641: An m-Health Application of Daily Text Messages to Address Forgetfulness as Contributor to Non-adherence to Medications Post-myocardial Infarction
Authors: Pandey Avinash , Choudhry Niteesh
Published: March 2022

Introduction:
Forgetfulness has been consistently identified as a contributor to non-adherence to medications. In post myocardial infarction (MI) patients, up to 50% of patients may remain non-adherent to medication at one year. Text message reminders to patients’ cell phones could be a cost-effective method to reduce medication non-adherence.

Hypothesis:
It was hypothesized that daily text message reminders would improve adherence to medications in post-MI patients.

Methods:
This was a single center, randomized trial of text message system conducted in a cardiac rehabilitation facility. Patients post-MI on a once daily regimen of aspirin, a beta-blocker, an angiotensin converting enzyme inhibitor or angiotensin receptor blocker and a statin were recruited. Participants were randomized to usual care or to receive daily text messages at the prescribed timings indicating which medication that should be taken at each time. We performed pre-specified subgroup analysis in the elderly (age ≥ 65 years) and those with less education (grade 12 or less).

Results:
In a two month recruitment period, ninety patients were screened and thirty-four were randomized, 36% of which were female, and with an average age of 64 years. No significant baseline differences between intervention and controls patients were identified. In the control group, adherence fell from 92% after month 1 to 70% at month 12. In the intervention group, adherence dropped from 98% after month 1 to 90% at month 12 (p<0.0001 for difference between intervention and control at month 12). In all evaluated subgroups, text message reminders consistently improved adherence to medications. Reminders appeared to particularly effective in subgroups with lower baseline adherence such as the elderly and those with less education. In interviews, forgetfulness was identified as a leading cause of their non-adherence to medications.

Conclusions:
In post-MI patients, this study demonstrates significant improvement in adherence to medications with an automated, daily text message reminder system over one year of follow-up. Simple and scalable systems such as this text message reminder system may improve adherence to evidence-based therapies in this high risk population by addressing forgetfulness.