bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 10267: Thermogenic Modulation of Perivascular Adipose Tissue Ameliorates Cardioautonomic Deterioration in Prediabetes
Authors: AlZaim Ibrahim , Dwaib Haneen , Ajouz Ghina , Mougharbil Nahed , Ragi Marie-Elizabeth , MROUEH Ali , Refaat Marwan M , Obeid Omar , El-Yazbi Ahmed
Published: March 2022

Introduction:
Cardiac autonomic neuropathy, a risk factor of cardiovascular mortality, is a common manifestation of prediabetes. Evidence points to perivascular adipose tissue inflammation as a quintessential instigator of cardiovascular dysfunction in metabolic impairment. Interventions tailored to ameliorate such subtle cardiovascular involvement have not been forthcoming. Data emerging from our laboratory implicate alteration of adipocyte mitochondrial bioenergetics, particularly an upregulation of uncoupling protein 1 (UCP1) expression and subsequent augmentation of adipose tissue hypoxia, as a potential culprit driving localized adipose inflammation.

Hypothesis:
Inhibition of UCP1-mediated thermogenesis or activation of the alternative thermogenic pathway, futile creatine cycling, through supplementation with phosphate or creatine monohydrate, respectively, may ameliorate the inflammatory phenotype observed in non-obese prediabetic rats.

Methods:
A non-obese prediabetic rat model, developed in our laboratory was used. This phenotype is evoked by 12 weeks of hypercaloric feeding causing localized perivascular inflammation in absence of systemic markers of inflammation. Cardioautonomic function was assessed by invasive hemodynamics. Localized adipose tissue inflammation and macrophage polarization were examined.

Results:
UCP1 inhibition by phosphate supplementation reversed the blunted parasympathetic baroreflex sensitivity observed in prediabetic rats. This was associated with the alleviation of perivascular adipose tissue hypoxia, inflammation, and altered macrophage polarization. These changes were accompanied by normalization of metabolic efficiency that increased in prediabetic rats due to UCP1 upregulation. Similar functional effects were observed after creatine supplementation without changes in metabolic efficiency.

Conclusions:
Bypassing UCP1-mediated thermogenesis upregulated by increased caloric intake alleviates cardioautonomic deterioration triggered by perivascular inflammation. This is achieved by UCP1 inhibition with a potential risk of increased metabolic efficiency and weight gain, or by activation of the alternative thermogenic pathway of creatine cycling.
Abstract 10273: The Use of Direct Oral Anticoagulation Therapy in Transcatheter Aortic Valve Implantation in Patients with Concurrent Indications for Anticoagulation; A Systematic Review and Meta-Analysis
Authors: El Iskandarani Mahmoud , Al Tamari Ahmad , Khalid Muhammad , Paul Timir K
Published: March 2022

Introduction:
The optimal antithrombotic regimen in patients after transcatheter aortic valve implantation (TAVI) in the setting of concurrent indication for anticoagulation remains unclear. Recently multiple studies have investigated the role of direct oral anticoagulation therapy (DOAC) in comparison to Vitamin K antagonist (VKA) in this category of patients. Therefore, we conducted a systematic review and meta-analysis to evaluate the efficacy and safety of this approach

Hypothesis:
DOAC is a safe and effective alternative anticoagulation therapy in TAVI patients

Methods:
Unrestricted search of the PubMed, EMBASE, and Cochrane databases from inception till June 1, 2021, for studies comparing DOAC with VKA in TAVR patients with concurrent indication for anticoagulation. Relevant data were extracted and analyzed using Revman 5.3 software. Relative Risk (RR) and 95% Confidence interval (CI) were calculated using the random-effects model.

Results:
A total of 8 studies (7 Observational, and 1 Randomized clinical trial) were included examining 4,158 TAVI patients (1,500 DOAC vs 2,658 VKA). There was no difference between DOAC and VKA in terms of all-cause mortality RR 0.89 (95% CI 0.65-1.21), all-bleeding events RR 0.90 (95% CI 0.76-1.07), and stroke risk RR 1.42 (95% CI 0.96-2.11).

Conclusions:
DOAC is probably non-inferior to VKA in TAVI patients with concurrent indications for anticoagulation therapy. Further studies are needed to validate our findings.
Abstract 10282: Biventricular Shape Markers in Repaired Tetralogy of Fallot Associate with Pulmonary Valve Replacement Better Than Standard Clinical Indices
Authors: Govil Sachin , Mauger Charlene , Hegde Sanjeet , Perry James C , Young Alistair A , Omens Jeffrey H , McCulloch Andrew D
Published: March 2022

Introduction:
Current indications for pulmonary valve replacement (PVR) in repaired tetralogy of Fallot (rTOF) rely on global ventricular measurements but are inconsistently applied, lead to mixed outcomes, and are widely debated.

Hypothesis:
We aimed to test the hypothesis that specific regional markers of biventricular shape can discriminate differences in ventricular remodeling between rTOF patients that were and were not designated for follow-up PVR better than standard clinical indices.

Methods:
In this cross-sectional retrospective study, biventricular shape models were fit to CMR images from 84 rTOF patients. A statistical atlas of end-diastolic shape was constructed using principal component analysis. Multivariate regression was used to quantify shape marker and clinical index associations with subsequent intervention status (PVR, n=48 vs. No-PVR, n=36) while accounting for confounders. Clustering analysis was then used to test the ability of statistically significant shape markers and clinical indices to discriminate PVR status as evaluated by Matthews correlation coefficient (MCC). Geometric strain analysis was also conducted to assess shape marker associations with systolic function.

Results:
PVR status correlated with shape markers associated with RV apical dilation and LV dilation (p<0.001), RV basal bulging and LV conicity (p<0.02), and pulmonary valve dilation (p<0.002). PVR status also correlated with RV EF (p<0.03) and non-significantly correlated with LV ESVi (p<0.06). Clustering analysis revealed that shape markers discriminated PVR status better than clinical indices (MCC=0.49 and MCC=0.28, respectively). These shape markers were also significantly associated with RV and LV radial strain.

Conclusions:
Biventricular shape markers discriminated PVR status better than standard and current use clinical indices for PVR. These specific, regional features of cardiac morphology can provide mechanistic insight into adaptive vs. maladaptive types of ventricular remodeling that provide the foundation for clinical decision-making but may be overlooked when relying solely on global ventricular measurements.
Abstract 10290: The Relationship Between Brain Derived Neurotrophic Factor (BDNF) and Symptoms Following Catheter Ablation for Paroxysmal Atrial Fibrillation (AF)- NEURO-AF Study
Authors: Berbenetz Nicolas , Reed Jennifer , Birnie David H , Terada Tasuku , Mistura Matheus , Nery Pablo B , Redpath Calum J , Sadek Mouhannad M , Chen Li , Wells George A , Leenen Frans M , Tulloch Heather , Nair Girish M
Published: March 2022

Introduction:
Reduced BDNF concentrations have been observed in patients with depression and heart failure, with treatment and improvement in symptoms associated with increased concentrations. AF is associated with symptoms of depression and poor Quality of Life (QoL).

Hypothesis:
We hypothesized that patients without AF recurrence following catheter ablation would have higher BDNF concentrations, less depression severity, and improved QoL scores.

Methods:
A prospective observational study was conducted. BDNF (biosensis®
Rapid
™ ELISA) concentrations were performed and the Beck Depression Inventory-II (BDI-II), Short Form-36 Health Survey (SF-36) and AF Severity Scale (AFSS) were administered before and 12 weeks after catheter ablation. The primary outcome was change in BDNF blood concentrations following catheter ablation and its relationship with depression severity and AF related QoL.

Results:
One hundred patients with paroxysmal AF were recruited of which 98 completed the study. Eighty-nine patients were free of recurrent AF/atrial arrhythmias (AA) following catheter ablation. The baseline demographics and results are summarized in the accompanying table. Statistically significant changes were observed in BDNF concentrations, BDI scores and AFSS (perceived AF burden and symptoms) in patients without AF recurrence, after adjustments for CHADS2 score, age, and sex. The number of patients with AF recurrence were too few to make meaningful interpretation of results.

Conclusions:
BDNF concentrations significantly improved in subjects without AF recurrence after catheter ablation and were associated with a concomitant reduction in depression severity, perceived AF burden and symptoms of paroxysmal AF. Further research is required to determine the mechanism(s) that explain this novel association between BDNF and AF related symptoms.
Abstract 10301: Polygenic Risk Scores for Prediction of Atrial Fibrillation and Other Adverse Outcomes After Coronary Revascularization
Authors: Aittokallio Jenni , Kauko Anni , Vaura Felix , Salomaa Veikko , Kiviniemi Tuomas , Schnabel Renate , Niiranen Teemu
Published: March 2022

Introduction:
Both coronary heart disease and coronary procedures predispose patients to adverse events. To improve our understanding of the genetic factors underlying postoperative prognosis, we studied the association between polygenic risk scores (PRSs) and postprocedural complications in coronary revascularization patients.

Hypothesis:
We hypothesized that PRSs could improve risk prediction of postprocedural complications.

Methods:
The study sample comprised 8296, 6132, and 13082 participants of the FinnGen study who underwent percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG), or any revascularization, respectively. We genotyped the participants and identified adverse events during follow up of up to 30 years by record linkage with nationwide healthcare registers. We computed PRSs for each postoperative adverse outcome (atrial fibrillation [AF], myocardial infarction, stroke and bleeding complications) for all participants based on UK Biobank study GWAS summary statistics. We used multivariable-adjusted Cox proportional hazards models and c-statistics to examine the association between PRSs and outcomes.

Results:
A 1-SD increase in AF-PRS was associated with greater risk of postoperative AF with HRs of 1.22 (95% CI, 1.16-1.28), 1.15 (95% CI, 1.10-1.20) and 1.18 (95% CI, 1.14-1.22) after PCI, CABG, and any revascularization, respectively (Figure). In contrast, the association of the PRSs with other postoperative complications was non-existent to marginal. Inclusion of the AF-PRS in a model with a clinical risk score resulted in significant model fit improvement (increase in model c-statistic 0.0059-0.0098, depending on procedure type; P<0.0002 for all).

Conclusions:
The AF-PRS could be potentially used to improve AF prevention and clinical outcomes in revascularization patients.
Abstract 10309: Pregnancy Outcomes in Women with Hypertrophic Cardiomyopathy
Authors: Moolla Muhammad , John Kevin J , Yogasundaram Haran , ALHUMAID WALEED , Campbell Sandra , Windram Jonathan , Mathew Anoop
Published: March 2022

Introduction:
Hypertrophic cardiomyopathy (HCM) is a genetic disorder often complicated by heart failure, embolic stroke, and sudden cardiac death. Pregnancy causes hemodynamic changes which may be deleterious in patients with HCM. Existing cohort studies of maternal and fetal outcomes of pregnant patients with HCM are limited by small sample sizes. We performed a systematic review of maternal and fetal outcomes of pregnancy in patients with established HCM.

Methods:
We searched MEDLINE, EMBASE, and Cochrane Library databases for studies reporting maternal or fetal outcomes in pregnant patients with HCM. The primary outcomes were maternal death, stillbirth, and fetal death. Secondary maternal outcomes included: sustained ventricular tachycardia (VT), any VT (including sustained and non-sustained), atrial fibrillation (AF), syncope, caesarean delivery, and pre-eclampsia or eclampsia. The secondary fetal outcome was preterm birth. We used a random effects model to determine pooled incidences of outcomes.

Results:
A total of 18 studies with 5236 pregnancies were included. The incidence of maternal death was 0.2%. Similarly, the incidence of neonatal death was 0.2%. The incidence of maternal and neonatal death was too low across studies to derive pooled estimates. The rate of stillbirth was low at 1% (95% CI, 0-3%) and rate of preterm birth was 22% (95% CI, 18-25%). The rates of sustained VT, any VT, AF, heart failure, and syncope were 1% (0-1%), 6% (4-8%), 4% (2-6%), 5% (3-8%), and 9% (3-14%), respectively. Postpartum hemorrhage, preeclampsia or eclampsia, and cesarean section complicated 2% (1-4%), 4% (2-6%), and 43% (32-54%) of pregnancies, respectively.

Conclusions:
Women with HCM looking to become pregnant can be reassured that the risk of death, stillbirth, or neonatal demise are low. However, they are at risk for several non-fatal cardiac and pregnancy related complications.
Abstract 10315: Cost-Effectiveness of Bempedoic Acid in Patients with Established Atherosclerotic Cardiovascular Disease
Authors: Butala Neel M , Virani Salim S , Isaza Nicolas , Lin Grace A , Pearson Steven , Bellows Brandon , Liu Chia Liang , Aggarwal Rahul , Zhang Yiyi , Kazi Dhruv S
Published: March 2022

Introduction:
Non-statin therapies may improve long-term outcomes in patients with atherosclerotic cardiovascular disease (ASCVD) who experience statin-associated side effects (SASE).

Objective:
To examine the cost-effectiveness of a newly approved combination of bempedoic acid and ezetimibe (BAEze) in patients with ASCVD from a U.S. healthcare sector perspective.

Methods:
State-transition Markov model of US adults with ASCVD and low-density lipoprotein cholesterol (LDL-C) ≥70mg/dL on maximally tolerated statin and ezetimibe. The study cohort was stratified by concurrent statin use: high-intensity (group1), moderate-/low-intensity (group 2), or no statin due to severe SASE (group 3). The intervention group received BAEze (annual cost $2,447) instead of ezetimibe. We estimated baseline LDL-C from NHANES; relative LDL-C lowering and rate of adverse events from randomized trials; and the relationship between LDL-C lowering and cardiovascular events from meta-analyses of statin trials. The main outcome was lifetime incremental cost-effectiveness ratio (ICER), with a threshold of $100,000 per quality-adjusted-life-year (QALY) gained.

Results:
BAEze had an ICER of $188,000/QALY in group 1 (95% UI: 141,500-284,600; cost-effective in 0% of 10,000 probabilistic simulations) and $175,600/QALY (132,700-264,700; cost-effective in 0% simulations) in group 2. In group 3, BAEze produced 0.28 incremental QALYs at a lifetime cost of $25,600, yielding an ICER of $92,600/QALY (66,000-152,100; cost-effective in 59% simulations).

Conclusions:
Among US adults with ASCVD, cost-effectiveness of BAEze varies substantially by concurrent statin use, and only meets conventional cost-effectiveness thresholds among patients unable to take a statin due to severe SASE. Our findings argue for the selective use of BAEze among patients with ASCVD and severe SASE but should be updated when more data on long-term effectiveness and safety become available.
Abstract 10319: Community Socioeconomic and Urban-Rural Differences in Emergency Medical Services Time Intervals for Suspected Stroke Patients in North Carolina
Authors: Chari Srihari V , Cui Eric R , Fehl Haylie E , Fernandez Antonio R , Brice Jane H , Patel Mehul D
Published: March 2022

Introduction:
Rapid emergency medical services (EMS) response, care, and transport of acute stroke patients increases the likelihood of receiving time-sensitive treatment. There is limited research on the relationship of community factors with prehospital delays in EMS management of stroke. We compared EMS prehospital time intervals for suspected stroke patients by community socioeconomic status (SES) and urban-rural status in North Carolina (NC).

Methods:
We analyzed 2019 NC EMS encounter data collected in the National EMS Information System Version 3 standard. Eligible patients were adults requiring a 911 call response by EMS for stroke-like symptoms and transport to the hospital. Incident street addresses were geocoded to census tracts using ArcGIS Pro and linked to SES data from the American Community Survey and rural-urban commuting area (RUCA) codes. Community SES was defined as high, medium, or low based on tertiles of the AHRQ SES index. Urban, suburban, and rural tracts were defined by RUCA codes 1, 2-6, and 7-10, respectively. Differences in mean times by community SES and urban-rural status were evaluated using Kruskal Wallis tests.

Results:
We identified 17,117 eligible EMS encounters of suspected stroke (65% (11,121 of 17,117) 65+ years old; 55% (9,330 of 17,117) female; 70% (11,839 of 17,117) White) from 2,028 tracts. Median response, scene, and transport times were 8 (interquartile range, IQR 6-11) min, 16 (IQR 12-20) min, and 14 (IQR 9-22) min, respectively. Mean transport times were shorter in low SES (16 min) than in medium and high SES communities (17 min, p<.0001). Mean transport times were longer in rural (21 min) and suburban (19 min) than in urban tracts (14 min, p<.0001).

Conclusions:
EMS transport times were on average longer for suspected stroke patients in rural but not in low SES tracts. Further research is needed on the role of community socioeconomic deprivation and rurality in contributing to delays in prehospital stroke care.
Abstract 10320: Feasibility of the Telehealth Assessment and Skill-Building Kit for Stroke Family Caregivers
Authors: Bakas Tamilyn , Sucharew Heidi , Brehm Bonnie J , Dunning Kari , McCarthy Michael J , Rota Matthew , Israel Jahmeel , Stacy Kelly E , Kissela Brett M , Miller Elaine L
Published: March 2022

Introduction:
Existing stroke family caregiver interventions are limited in the use of technology and lack focus on caregiver health. The Telehealth Assessment and Skill-Building Kit (TASK III) was optimized based on caregiver preferences for technology and goal setting to improve caregiver health. The purpose of this study was to test feasibility of the TASK III program compared with an Information, Support, and Referral group (ISR) for improving caregiver depressive symptoms, life changes, and unhealthy days.

Methods:
Using randomized control trial design and an intent-to-treat analysis, 74 stroke family caregivers were randomized to TASK III (n=36) or ISR (n=38). The TASK III Resource Guide was provided by hard copy, website, eBook, and USB drive. TASK III and ISR groups received an American Stroke Association (ASA) pamphlet, access to the ASA website, and 8 weekly calls from a nurse (telephone/videoconferencing), with a booster call a month later. Data trends from baseline to 8 and 12 weeks were explored for depressive symptoms (PHQ-9), life changes (Bakas Caregiving Outcomes Scale), and unhealthy days. Minutes on calls with the nurse were controlled in analyses.

Results:
Among caregivers with mild to severe depressive symptoms at baseline (PHQ-9
>
5) (n=31), TASK III showed a greater reduction in depressive symptoms relative to ISR from baseline to 8 and 12 weeks (Mean group difference in change scores -3.7, p=.02 at 8 weeks; -3.7, p=.04 at 12 weeks). Using the full sample (N=74), life changes improved for TASK III relative to ISR from baseline to 8 and 12 weeks (Mean 8.1, p=.03; 14.9, p<.01), and for specific life changes of emotional well-being (Mean 0.8, p=.05; 1.4, p=.01) and physical health (0.7, p=.07; 1.2, p<.01). No significant differences in rate ratios were found for unhealthy physical (Rate ratio 1.7, p=.17; 1.1, p=.74) and mental days (Rate ratio 1.4 p=.22; 1.4, p=.25).

Conclusions:
Data trends supported feasibility of TASK III relative to ISR for improving depressive symptoms and life changes, including changes in emotional well-being and physical health. Unhealthy days were highly skewed and not sensitive to change. Testing efficacy of TASK III relative to ISR is warranted in a future, well-powered trial.
Abstract 10324: Characterization and Impact of Covid-19 on Heart Transplant Recipients
Authors: Kanaan Christopher , Iskandar Jean Pierre , Gad Mohamed , Kondoleon Nicholas , Fares Maan , Hsich Eileen M , Estep Jerry
Published: March 2022

Introduction:
Heart transplant recipients who subsequently acquire COVID-19 may be at an increased risk of severe disease and adverse outcomes, particularly in light of several comorbidities and chronic states of immunosuppression.

Methods:
In this retrospective case-control analysis, we compared the outcomes of heart transplant patients with confirmed COVID-19 to matched, COVID-19 positive, non-transplant patients at the Cleveland Clinic. The transplant group included adult patients who were hospitalized with COVID-19 between March 2020 and March 2021. The controls were matched 2:1 (24 heart transplant, 48 non-heart transplant) on different baseline characteristics. The primary outcome was in-hospital mortality and secondary outcomes were the length of hospital stay (LOS), need for mechanical ventilation, ICU admission, pressor requirements (norepinephrine, epinephrine, vasopressin), dialysis requirement, pneumonia incidence, and 30- day readmission within the COVID-19 diagnosis window. All tests had a 2-sided significance level of 0.05.

Results:
Of 11,505 patients with COVID-19 infection, 72 post-match were included in the final analysis. The mean age of hospitalized heart transplant recipients was 62 ±18, 70% were Caucasian, 87.5% were male, 47% had a smoking history, 17% had COPD, and 8% had asthma. Primary outcome of in-hospital mortality in the heart transplant COVID group vs. non-transplant COVID group was 12.5% and 14.6%, respectively (OR: 0.84; 95% CI 0.2-3.57). There was no statistically significant difference in median LOS (more than 7 days; 45.8% vs. 52.1%; OR: 0.78; 95% CI 0.29-2.08), need for mechanical ventilation (16.7% vs. 14.5%; OR: 1.17; 95% CI 0.31-4.47), ICU admissions (33.3% vs. 35.4%; OR: 0.91; 95% CI 0.32-2.57) pressor requirements (8.3% vs. 8.3%; OR: 1; 95% CI 0.17-5.89), dialysis needs (4.1% vs. 6.2%; OR: 0.65; 95% CI 0.06-6.63), pneumonia (4.2% vs. 8.5%; OR 0.48: 95% CI 0.05-4.53), or 30-day readmission (17.4% vs. 8.5%; OR: 2.26; 95% CI 0.51-10.02).

Conclusion:
Our study suggests that heart transplant recipients who acquire and are hospitalized for COVID-19 do not show worse in-hospital outcomes compared to those of their matched non-transplant cohorts. However, the study results are limited due to sample size.
Abstract 10333: Recreational Multi Use Trails and Cardiovascular Disease: A Difference-in-Differences 18 Year Natural Experiment
Authors: McGavock Jonathan M , Hobin Erin , Prior Heather , Swanson Anders , Booth Gillian , Rosella Laura , Whitehouse Stephanie , Smith Brendan , Russell Kelly , Brunton Nicole , Burchill Charles
Published: March 2022

Introduction:
There is little experimental evidence of the impact of multi-use recreational trails that support physical activity on cardiovascular disease (CVD).

Hypothesis:
Neighbourhoods that added multi-use trails would experience a greater decline in CVD events and risk factors compared to neighbourhoods that did not.

Methods:
We used a difference in differences design to study the addition of four multi-use trails 4-7km in length on CVD-related outcomes using administrative health, census and built environment data available for all citizens 30 years of age and older from Winnipeg, Canada. A 400m buffer stratified intervention and comparison neighbourhoods. Bicycle counts were recorded via electromagnetic counters for 5 years on all trails. The primary and secondary outcomes were composite measures of incident CVD events (mortality, ischemic heart disease, cerebrovascular disease and congestive heart failure) and CVD risk factors (hypertension, diabetes and dyslipidemia) and assessed quarterly for 10 years prior to and 6 years following the intervention. Intervention and comparison areas were propensity score matched, using scores regressed from baseline measures of age, sex, socioeconomic indicators, and built environment attributes that support physical activity.

Results:
Between 2012 and 2018, 1,429,588 cyclists were recorded on the trails and cycling use varied ~2.0-fold across the trails. Between 2000 and 2018, there were 82,632 CVD events and 201,058 CVD risk events. During the 18-year natural experiment CVD event rates and risk factors declined ~33% in both comparison and intervention neighbourhoods. In propensity score matched regression models, the incident rate ratio was 1.06 (95% CI: 0.90 to 1.24) for CVD events and 0.92 (95% CI: 0.84 to 1.02) for CVD risk factors. Sensitivity analyses revealed greater effect sizes with increasing trail use (incident rate ratios for highest vs lowest cycling counts = 0.85; 95% CI: 0.75 to 0.96 vs 1.08; 95% CI: 0.92 to 1.27).

Conclusions:
The addition of recreational multi-use trails was not associated with changes in overall CVD events or risk factors in adjacent neighbourhoods, compared to distant neighbourhoods, however, the effects on CVD risk factors may be influenced by trail use.
Abstract 10346: Peripheral Vascular Disease Hospitalizations with Cardiovascular Disease Risk and Major Adverse Cardiac and Cerebrovascular Events Occur at Increasingly Younger Age Across Two Nationwide Cohorts Selected 10-Years Apart
Authors: Desai Rupak , Shanker Srija , Nepal Ashish , Singla Tanvi , Mohammad Aamer , Joseph Deepu , Fatima Bushra , Ali Khan Mir Zeeshan , Vyas Ankit
Published: March 2022

Introduction:
There have been increasing hospitalizations among young adults for peripheral vascular disease (PVD) in the last decade. We compared the mean age of young PVD admissions with cardiovascular comorbidities and major adverse cardiac and cerebrovascular events (MACCE) across two national cohorts 10-years apart.

Methods:
Two nationwide cohorts from 2007 and 2017 were analyzed for mean age at presentation with CVD risk factors and MACCE in young (18-44 years) PVD hospitalizations. Age at admission was reported as Mean± SD and compared between two groups using student’s t-test.

Results:
A total of 37,099 admissions in 2007 and 46,760 admissions in 2017 were identified for PVD among young adults. Total admissions increased from 0.4% to 0.5%.The 2017 cohort showed that non-elective PVD admissions occurred at significantly younger age (mean 35 vs 38 years) compared to 2007 cohort. Patients with PVD had comorbid risk factors including hypertension, diabetes mellitus, smoking, obesity, and congestive heart failure (CHF) with a mean age of 39±5 years at presentation in 2007 which decreased to 38±6 years for hypertension and diabetes, 36±6 years for smoking and 37±6 years for CHF and obesity (p<0.001) in 2017. Mean age for MACCE in PVD was 39±5 years in 2007 cohort which significantly reduced to 36±7 years in 2017 (p<0.001)
(Table 1).
Acute myocardial infarction, cardiogenic shock and PCI procedures were recorded at a younger age in 2017 PVD cohort vs. 2007 PVD cohort. Similarly, the 2017 PVD cohort included relatively younger patients experiencing ventricular tachyarrhythmias and stroke.

Conclusions:
This study from two young cohorts selected 10-years apart shows increasing trends in PVD hospitalizations occurring at a significantly younger age with associated cardiovascular comorbidities and MACCE in recent years. The link between young age and complicated/severe PVD admissions with frequent comorbidities should be further investigated.
Abstract 10348: Incidence and Characterization of Inpatient Complications Occurring More Than 48 Hours Post Stemi
Authors: Patel Krina , Tangellamudi Dhruva T , Andrus Bruce W , Devries James T , Niles Nathaniel
Published: March 2022

Background:
With continued reductions in ST-elevation myocardial infarction (STEMI) mortality and an interest in reducing length of stay (LOS), the question of which patients require extended inpatient monitoring remains uncertain.

Methods:
We present a single center retrospective study of consecutive patients admitted with STEMI undergoing emergent percutaneous intervention (PCI) from 2009-2018 (n=500). We identified subjects using the catheterization lab database and then reviewed the medical record for the following events occurring 48 hours or more following PCI: acute kidney injury (AKI), stent thrombosis, acute bleeding, falls with injury, use of mechanical support, use of vasopressors, cardiogenic shock, arrhythmias, ventricular rupture, papillary muscle rupture, pericarditis, heart failure requiring intravenous diuresis, re-admission within 48 hours of admission, and death. We hypothesized that elderly patients with multiple comorbidities would be at increased risk of late inpatient complications.

Results:
The average length of stay was 3.9 days and 384/500 patients stayed longer than 48 hours. Predictors of LOS beyond 48 hours included a left-anterior descending (LAD) culprit lesion (p= 0.04) and chronic kidney disease (CKD) (p=0.03). Risk factors for complications occurring beyond 48 hours included PCI of the LAD (increased risk of heart failure, p=0.003), older age (increased risk of cardiogenic shock, p=0.02), male sex (increased risk of requiring intravenous diuresis, p=0.01) and an initial Thrombolysis in Myocardial Infarction (TIMI) flow of 0 (increased risk of requiring vasopressors, p=0.005).

Conclusion:
In our sample, STEMI involving the LAD and CKD were associated with a prolonged hospital stay. Patients undergoing PCI of the LAD, and those with initial TIMI 0 flow, older age, and male sex should be strongly considered for extended inpatient monitoring.
Abstract 10351: Validity and Relevance of Clinical Worsening as a Composite Endpoint in Pulmonary Arterial Hypertension Trials
Authors: Mai Vicky , Tremblay Elodie , Gosselin Camille , Lajoie Annie Christine , Yves Lacasse , Lega Jean-Christophe , Bonnet Sebastien , Provencher Steeve
Published: March 2022

Background:
Clinical worsening (CW) is commonly used as an endpoint in pulmonary arterial hypertension (PAH) trials. The use of composite endpoints is based on the assumption that each component is interchangeable.

Objectives:
We aimed to assess the trial-level surrogacy of CW for predicting overall mortality (considered adequate when coefficient of determination R
2
trial
>0.70) in PAH trials. We also assessed whether the various CW components were similar in terms of: 1) frequency of occurrence; 2) treatment-related relative risk (RR) reduction and; 3) importance to patients.

Methods:
We searched MEDLINE, Embase, and the Cochrane Library (01/1990-12/2020) for RCTs evaluating the effects of PAH treatment on CW. The R
2
trial
between the RR for CW and mortality (including after censoring) was analysed by regression analysis. The frequency of occurrence of the CW components, as well as the RR reduction of the CW components and those considered of critical, major and mild-to-moderate importance determined through a web-based survey on 257 PAH patients were assessed.

Results:
From 4,778 references, we included 35 studies (7,744 pts). The effects of PAH-specific therapies on CW modestly correlated with mortality (R
2
trial
0.32). Most of the CW defining-events were PAH-related hospitalizations (30.5%) and symptomatic progressions (48.0%), whereas deaths (14.1%), treatment escalations (6.8%) and transplantations or atrial septostomies (0.6%) were unusual. The RR across components differed by >0.4 in 20/35 studies (57%). Furthermore, the composite endpoints combined components of both critical to moderate importance to patients in 31/35 studies (89%). The pooled treatment effects only became significant when endpoints of major (RR 0.67;95%CI 0.60-0.74;p<0.01) and moderate (RR 0.61;0.52-0.70;p<0.01) importance to patients were added to critical outcomes (RR 1.02;95%CI 0.78-1.32;p=0.91). Consistently, 8/12 (67%) trials with documented decreases in CW were no longer significant when outcomes of moderate importance to patients were excluded.

Conclusion:
CW is not a surrogate outcome for mortality in PAH trials. Moreover, components of CW largely vary in frequency, response to therapy and importance to patients and are thus not interchangeable.
Abstract 10356: Impact of Statin Therapy in Heart Failure Patients: Results of a Large Real-World Experience
Authors: Anderson Jeffrey L , May Heidi T , Le Viet T , Muhlestein Joseph B , Horne Benjamin D , Bair Tami L , Knight Stacey , Knowlton Kirk U
Published: March 2022

Introduction:
The use of statins in patients (pts) with heart failure (HF) is controversial. In patients without HF, statins reduce the risk of atherosclerotic cardiovascular disease (ASCVD), including HF-related events. In contrast, no benefit was observed in statin-treated HF pts in the CORONA and GISSI-HF trials. However, issues with generalizability may limit the applicability of these trial results in clinical practice. Therefore, we analyzed the impact of statin therapy in systolic HF pts in a large real-world experience.

Methods:
We searched Intermountain Healthcare medical records for pts with a diagnosis of HF and a reported ejection fraction of <=40%. We compared outcomes (MACE=death, MI, stroke) at a median of 4.5 years follow-up in those who were and were not prescribed a statin. Statin use was defined as use at or after a HF diagnosis but prior to 60-days before MACE or end of follow-up. Cox hazard regression analysis was used to determine hazard ratios.

Results:
A total of 15,010 pts were studied. Baseline demographics and outcomes are shown in the Table. Statin use was associated with more frequent ASCVD risk factors yet a lower MACE risk during follow-up. Benefit was similar for primary and secondary prevention pts and for prior and new statin prescriptions. By time-varying hazard ratio (HR) analysis, the longer the pt was on a statin, the greater the reduction in risk of MACE (p<0.0001).

Conclusion:
These results suggest a potential benefit of selective statin use in the real-world management of HF pts with ASCVD or at high-ASCVD risk. These novel observations deserve validation in additional real-world experiences.
Abstract 10363: Mitochondrial DNA Copy Number is Associated with Severe Coronary Artery Disease and Risk of Subsequent Long-Term Major Adverse Cardiovascular Events
Authors: Knight Stacey , Dong Li , Galenko Oxana , Juan James , Muhlestein Joseph B , Anderson Jeffrey L , Knowlton Kirk U , Carlquist John F
Published: March 2022

Introduction:
Mitochondrial DNA copy number (mtDNA-CN) is associated with cardiovascular disease (CVD) and mortality. Here we examine, in a high-risk CVD population, the association with prevalent coronary artery disease (CAD) and subsequent major adverse events (MACE) at 1-,5- and 10-year follow-up of mtDNA-CN.

Methods:
Consecutive subjects (n=2267) consenting to a blood sample drawn for the Intermountain INSPIRE biorepository at the time of a coronary angiogram from July 1994 to Sept 2003 were included. The mtDNA-CN was determined by multiplexed real-time polymerase chain reaction coamplifying a stable site of mt D- Loop and a region of a single copy genomic β-2-microglobulin gene(β2M). MtDNA-CN is given as the ratio of Mt to β2M DNA. The presence of severe CAD (>70% stenosis) was analyzed using multivariate logistic regression. The subsequent MACE (including all-cause mortality and non-fatal MI) outcomes were studied using multivariate Cox proportional hazard regression.

Results:
The average age of subjects was 62.3 ± 13.8, 35% were female, and 50% had prior CAD. Over half (55%) had severe CAD at the angiogram. As the mtDNA-CN increased, severe CAD decreased (58% for 1
st
quartile vs. 51% for 4
th
quartile). After adjustment for baseline differences, subjects with mtDNA-CN in the 1
st
quartile were 1.31 times more likely to have severe CAD than subjects with mtDNA-CN in the 4
th
quartile (95% CI: 1.01, 1.71; p=0.04). A total of 902(39.8%) had a subsequent MACE event within 10-years (193[8.5%] in 1-year and 548[24.2%] in 5-years). There was no association between mtDNA-CN and 1-year MACE. However, mtDNA-CN was associated with 5-year (p=0.006) and 10-year (p=0.003) MACE. After adjustment, subjects with mtDNA-CN in the 1
st
quartile were at 1.29 increased risk of 10-year MACE than subjects with mtDNA-CN in the 4
th
quartile (95% CI: 1.07, 1.56; p=0.008).

Conclusions:
In a coronary angiographic population, mtDNA-CN was associated with severe CAD and the risk of subsequent long-term MACE. These findings suggest that mtDNA-CN could be used as a clinical biomarker for risk. Moreover, understanding the factors impacting mtDNA-CN may also help in the prevention of secondary CVD outcomes.
Abstract 10372: A Clinical Drug-Drug Interaction Study of Imb-1018972, a Novel Investigational Cardiac Mitotrope in Phase 2 Development for the Treatment of Myocardial Ischemia and Hypertrophic Cardiomyopathy
Authors: Tremaine Larry , Al-Fayoumi Suliman , van de Wetering Jeroen , van Iersel Thjis , Patel Jaikrishna , Chamberlin Paul
Published: March 2022

Background:
IMB-1018972 (IMB-101) is a novel mitotropic agent designed to increase myocardial metabolic efficiency by shifting substrate utilization towards glucose through reducing fatty acid oxidation (inhibiting 3-ketoacyl CoA thiolase), thereby generating more ATP per unit of oxygen consumed. IMB-101 is hydrolyzed to IMB-1028814 (IMB-102, the active moiety) which is further metabolized with ~60% forming trimetazidine (TMZ). In vitro cytochrome P450 (CYP) studies reveal IMB-102 to be metabolized by multiple CYPs with CYP2C19 and CYP2D6 potentially comprising a major portion of its clearance and formation of TMZ. IMB-101 is under evaluation in Phase 2 studies in stable CAD, non-obstructive HCM & T2DM, indications for which patients often take multiple medications concurrently.

Aim:
To evaluate the drug-drug interaction (DDI) potential of IMB-101 in healthy subjects.

Methods:
A fixed sequence crossover study conducted in 3 parts evaluating the effect of: 1) multiple dose oral (PO) IMB-101 on the single dose PK of PO CYP3A4 (midazolam) and CYP2C8 (repaglinide) substrates (n=23); multiple doses of strong inhibitors of 2) CYP2D6 (paroxetine) or 3) CYP2C19 (fluvoxamine) on the single dose PK of PO IMB-101 (n=14 each).

Results:
1) Weak inhibition of CYP2C8 by IMB-101 based on AUC of repaglinide but none based on its Cmax. Weak inhibition of CYP3A4 by IMB-101 based on AUC and Cmax of midazolam. 2) Limited involvement of CYP2D6 in the metabolism of IMB-102 to metabolites other than TMZ based on IMB-102 AUC and Cmax when given with paroxetine. 3) A major role for CYP2C19 in the metabolism of IMB-102 to TMZ in vivo evidenced by increased IMB-102 exposure and reduced TMZ exposure when given with fluvoxamine. Based on the summation of AUCs for the active entities (IMB-102 and TMZ), exposure is unchanged with co-administration of fluvoxamine suggesting no IMB-101 dose adjustment is needed with concurrent strong CYP2C19 inhibition.

Conclusions:
IMB-101 does not result in clinically significant inhibition of CYP3A4 or 2C8 isoenzymes and its metabolites are not clinically relevant CYP2D6 substrates. These findings support the administration of IMB-101 with commonly used cardiovascular medications without a significant risk of DDI or requirement for dose alterations.
Abstract 10397: Prevalence and Outcomes of Primary Cardiomyopathy in Marfan Syndrome
Authors: Connor Brynn S , Algaze Claudia A , Collins Ronnie T
Published: March 2022

Introduction:
Cardiovascular disease is the leading cause of morbidity and premature mortality in Marfan Syndrome (MFS), with ≥ 50% of patients developing a secondary, dilated cardiomyopathy from chronic valvular regurgitation. Apart from significant valvular disease, patients with MFS have evidence of systolic dysfunction, suggestive of a primary cardiomyopathy. However, prior cross-sectional studies have been limited by small sample sizes and short durations of follow-up. Our aim was therefore to determine the true prevalence and long-term outcomes of a primary cardiomyopathy in MFS.

Methods:
We performed a retrospective chart review of all adult patients with a confirmed diagnosis of MFS followed at Stanford Health Care. Those with significant valvular dysfunction (≥moderate aortic or mitral regurgitation), coronary artery disease, or prior cardiac surgery were excluded. Myocardial dysfunction (MD) was defined as a left ventricular ejection fraction (EF) <55%, as assessed by echocardiography or on cardiac MRI. Genetic, sociodemographic, and potential cardiac risk modifiers were also recorded.

Results:
A total of 753 patients with confirmed MFS were identified and followed over a median of 8 years (IQR 4, 13). Of the initial cohort, 241 patients (47% male, 71% Caucasian) met inclusion criteria and defined the at-risk population. MD was present in 30 patients (12.4%), with a median age of onset at 32 years (IQR 24.5, 44.8), median EF of 50.9% (IQR 48.0, 53.8), and evidence of clinical heart failure (NYHA Class ≥2) in 10% of patients. There was no significant association with the majority of queried sociodemographic and traditional cardiovascular risk variables. MD was more commonly observed in patients with larger aortic root diameters (aortic root ≥ 4.0 cm: AOR=4.2, 95% CI=1.2-15.0, p=0.03); however, corresponding use of goal-directed medical heart failure therapies did not appear to be protective against the development of MD (p=0.5).

Conclusions:
Even in the absence of significant valvular pathology, MD is prevalent in MFS from a young age, indicative of a primary cardiomyopathy. While dysfunction is often subclinical and mild in nature, it can progress across the lifespan and appears to be refractory to standard medical heart failure therapies.
Abstract 10414: Audit of Percutaneous Coronary Intervention Use in St-Elevation Myocardial Infarction Under the Indian National Health Insurance Program Ayushman Bharat
Authors: Duggal Bhanu , Chourase Mithlesh , Sharma Nupur , Duggal Mona , Gedam Praveen , Saunik Sujata , Agrawal Ajai , Nallamothu Brahmajee K
Published: March 2022

Introduction:
National health insurance programs like Ayushman Bharat (AB) have increased access to treatments like PCI to poor patients in low-to-middle income countries (LMICs). Evaluating such systems for STEMI care through electronic health records (e-HR) data can provide a unique opportunity to assess quality of PCI.

Methods:
We evaluated PCI cases within AB across 5 Indian states, selecting 4 hospitals from each state (2 public & 2 private facilities). Each week from January to May 2020, we selected 5 random cases from each hospital for detailed review. We accessed e-HR data of these patients. To ensure data quality, data was double abstracted at two different time points. We report descriptive statistics focused on the timing of PCI relative to their symptom onset and first medical contact (FMC).

Results:
Of 300 PCIs reviewed within AB, 196 patients were managed for STEMI. A total of 47 from Uttar Pradesh, 53 from Chhattisgarh, 43 from Maharashtra, 28 from Madhya Pradesh, and 25 from Haryana. Of these, 59.7% (117/196) patients reached FMC within 3 hours of symptom onset; 17.9% (35/196) within 3-12 hours, 5.1% (10/196) within 12-48 hours, 3.1% (6/196) within 48-72 hours, and 12.8% (25/196) after 72 hours. From FMC, PCI was done in only 4.6 % (9/196) patients within 3 hours and 8.7 % (17/196) within 12 hours. Over half (107/196 or 54.6%) received PCI after 72 hours (Figure). Of these, only 3/107 (2.8%) received fibrinolytic therapy and 35/107 (32.7%) had complete occlusion of the culprit vessel, nullifying the benefit of PCI based on randomized trial evidence.

Conclusion:
Many poor Indian patients undergoing PCI for STEMI under AB are receiving PCI after long delays with underuse of fibrinolytic therapy. Opportunities to improve reperfusion therapy in India exist for socioeconomically disadvantaged patients.
Abstract 10416: Rising Trends in the Burden of Cardiovascular Comorbidities and Major Adverse Cardiovascular Events in Young Female Smokers Across Two Nationwide Cohorts Studied a Decade Apart (2017 vs. 2007)
Authors: Desai Rupak , Sura Harsh , Agha Khizran , Sasidharan Nayana , Badarabandi Umarani , Bansal Prerna , Hiba Ambreen NFN , Sachdeva Sonali , Jain Akhil
Published: March 2022

Background:
Ample evidence has suggested that female smokers are at a higher risk of smoking-related health problems compared to men. With the increasing number of young smokers in the US, there is limited data on the impact of smoking in young female smokers in the last decade.

Methods:
The National Inpatient Sample datasets (2007 and 2017) were utilized to identify hospitalizations among young (18-44 years) female tobacco smokers. We compared differences in frequency of admissions, comorbidity burden, and in-hospital outcomes (all-cause mortality and MACE) and resource utilization across two young cohorts 10-years apart.

Results:
A total of 1,224,479 (median age 32) admissions among young female smokers were identified in 2017 vs. 665,901 (median age 35) in 2007. Both cohorts showed the majority of admissions among white female smokers, followed by African Americans
(Table 1)
. Compared to the 2007 cohort, the rate of alcohol abuse, hyperlipidemia, uncomplicated diabetes and chronic pulmonary disease decreased inn 2017, whereas a rising trend was observed for deficiency and chronic blood loss anemias, diabetes with complications, drug abuse, hypertension, congestive heart failure, depression, liver disease, and obesity (p<0.001). On adjusted multivariable analysis, the 2017 cohort showed significantly higher odds of all-cause mortality [aOR 1.25 (95%CI: 1.16-1.35)] with a higher risk of MACE [aOR 1.17 (95%CI:1.14-1.20)] (p<0.001). There were fewer routine discharges and higher requirements of home health care in the 2017 cohort vs. 2007.

Conclusion:
The study reveals escalating trends in the burden of comorbidities, MACE and healthcare resource utilization in admissions (irrespective of primary cause) among young female smokers in this decade apart analysis. It is essential to raise awareness among young female smokers about the adverse impact of tobacco and associated polysubstance abuse on cardiovascular outcomes.
Abstract 10417: Parity and Progression of Coronary Artery Calcium: The Multi-Ethnic Study of Atherosclerosis
Authors: Vu Kimberly , Michos Erin , FAN WENJUN , Evans Jonathan , Mongraw-chaffin Morgana , Budoff Matthew , Wong Nathan D
Published: March 2022

Introduction:
Coronary artery calcium (CAC) is a measure of subclinical atherosclerosis and predicts cardiovascular disease (CVD) events. Higher parity, the number of live births, has been shown to relate to CVD. We examined whether parity is associated with progression of CAC as one pathway to CVD.

Methods:
We studied 2772 women aged 44 to 84 years free of CVD at baseline in the prospective Multi-Ethnic Study of Atherosclerosis. Parity was examined continuously as number of live births as well as by categories: 0-1 (reference), 2-3, and ≥4 in relation to change in CAC score from baseline to follow-up from repeat exams up to 11 years later. We used linear mixed effect models to account for repeated measures when assessing whether progression of CAC was associated with parity, adjusted for baseline CAC and other risk factors.

Results:
Women with higher parity had greater annualized progression of CAC scores (unadjusted p<0.01) (figure). Using linear mixed effects modeling adjusted for age, ethnicity, baseline CAC scores, and other risk factors, parity was associated with progression of CAC (parity-CAC progression interaction terms): continuous parity (<0.0001), parity 2-3 vs 0-1 (p=0.06),
>
4 vs. 0-1 (p<0.0001).

Conclusion:
We show parity to be associated with the progression of CAC; this may help explain the increased CVD risk observed with higher parity and lends support to adding parity as a risk enhancing factor in women.