bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 13464: Association of Left Atrial Hemodynamics by Magnetic Resonance Imaging With Long Term Outcomes in Patients With Cardiac Amyloidosis
Authors: Arora Punit , Benjamin Mina M , Munir Muhammad , Darki Amir , LIEBO MAX , Yu Mingxi , Syed Mushabbar , Kinno Menhel
Published: June 2023

Introduction:
We investigated left atrial (LA) function and strain by MRI in patients with cardiac amyloidosis (CA) and their associations with clinical outcomes.

Methods:
We conducted a retrospective case control study of 51 CA patients (24 transthyretin [ATTR] and 27 systemic [AL]) and 51 age, gender, and race matched controls without cardiovascular disease who underwent MRI in sinus rhythm. We measured LA function and strain parameters including indexed volumes (LAVi), ejection fraction, expansion index, reservoir (εR), contractile (εCT), and conduit (εCD) strain. A multivariate regression model was adjusted for age, hypertension, NYHA class, modified staging system (using Troponin-I, BNP, and GFR) and left ventricular ejection fraction (LVEF). We used endpoints of all-cause mortality and a composite endpoint of heart failure hospitalization (HFH) or death.

Results:
Mean age was 65.3 for AL vs 76.2 for ATTR. ATTR patients had higher LAV, indexed LV and RV end systolic volumes and lower LVEF than AL patients. CA patients had significantly lower LA strain (11.5, 4.7, 6.8 vs 38.2, 14.2, 24 for εR, εCT, εCD respectively) and higher LAVs than controls. Median follow up was 12.6 months. εCT (OR 0.6, CI: 0.41-0.89), minimum LAVi (OR 1.06, CI: 1.02-1.13) and maximum LAVi (OR 1.08, CI: 1.01-1.15) were associated with the composite outcome of death or HFH. Cox Hazard regression models showed a difference in the composite outcome as LAVi increases and ↋CT is reduced. χ2 statistic were 23.1 for ↋CT versus 18.4 for LAVi (P=0.04, 0.01).

Conclusion:
In our retrospective study of CA patients, εCT, minimum and maximum LAVi were significantly associated with the composite outcome of death or HFH.
Abstract 13472: Physical Incapacity in Heart Failure Patients is Associated With Skeletal Muscle Mitochondrial Dysfunction
Authors: Tinggaard Andreas B , Skou Maria Kreiberg K , Sørensen Lotte , Seefeldt Jacob , Jessen Niels , Norrelund Helene , Wiggers Henrik
Published: June 2023

Introduction:
The role of skeletal muscle mitochondrial dysfunction in exercise intolerance in heart failure patients is unknown. Therefore, this study aimed to identify the relationship between physical capacity and skeletal muscle mitochondrial function in patients with heart failure and reduced ejection fraction (HFrEF).

Methods
A total of 53 HFrEF patients and 20 age- and sex-matched controls underwent dual-energy X-ray absorptiometry to assess muscle mass by the appendicular lean mass index (ALMI), cardiopulmonary exercise testing (peakVO2), 6-minute walking test (6MWD) and maximal isometric knee-extensor strength test. In skeletal muscle biopsies from vastus lateralis, mitochondrial respiratory capacity was measured by high resolution respirometry. We performed Pearson correlations to examine the relationships between physical capacity tests and mitochondrial function.

Results
Mean age of the study cohort was 71.7 ±7.0 years. Compared with healthy controls, HFrEF patients had a lower peakVO2 (14.6 ±4.1 vs. 26.2 ±8.0 mL/kg/min, p <0.001) and a shorter 6MWD (429 ±106 vs. 581 ±93 m, p <0.001). HFrEF patients had a lower ALMI (0.74 ±0.15 vs. 0.86 ±0.16 kg/(kg/m
2
), p = 0.005). Maximal coupled mitochondrial respiration was decreased in HFrEF patients compared with healthy controls (59.1 ±19.0 vs. 92.6 ±38.8 ρmol O
2
*s
-1
mg
-1
, p <0.001) as well as the respiratory control ratio (7.2 ±2.5 vs. 9.7 ±3.1). Maximal coupled mitochondrial respiration was correlated to peakVO2 (r = 0.58, p <0.001) and 6MWD (r = 0.44, p <0.001), but not to muscle mass or maximal knee-extensor strength.

Conclusions
HFrEF patients had a lower peakVO2, shorter 6MWD and impaired skeletal muscle mitochondrial function as compared with controls. Maximal coupled mitochondrial respiration was correlated with physical capacity across the population of HFrEF patients and healthy controls establishing an association between skeletal muscle mitochondrial dysfunction and physical incapacity.
Abstract 135: Regional Variation Of Adult Awareness Of And Likelihood To Perform Hands-only Cardiopulmonary Resuscitation
Authors: Turner Melanie B , Ferrer Jose M , Menon Sachin , Straccia Marida
Published: June 2023

Introduction:
About 75% of out-of-hospital cardiac arrests (OCHA) happen in the home. Based on US data, only about 40% of people who experience an OCHA receive bystander CPR before EMS arrives. Global community awareness data of Hands-Only CPR (HOCPR) and willingness to perform are limited.

Objective:
Determine global awareness of and likeliness to perform HOCPR among adults and examine regional variation.

Methods:
An online native language survey was administered among nationally representative samples of adults ≥18 years of age in 50 countries across 6 global regions. The survey was administered June-July 2021 using the YouGov RealTime omnibus service. The survey included one question regarding awareness of the concept of HOCPR as involving calling the local emergency number, and then pushing hard and fast in the center of the chest, but not involving breathing into the person’s mouth. A second question gauged willingness to perform HOCPR in an emergency on a 5-point scale. Participants were also able to answer “Don’t Know/Not Sure” to both questions. Results were weighted by country, then combined by region.

Results:
Of 47,488 adults (49.15% female), 66.79% reported awareness of HOCPR. Regional awareness ranged from 58.75% to 79.07%. Of those who were aware of HOCPR, 77.72% were extremely, very likely, or somewhat likely to give HOCPR in an emergency (regional range, 74.09% to 88.01%). Globally, awareness increased likeliness by 44.54%. In every region, there were no awareness differences between men and women (p=0.90); however, men were more likely than women to give HOCPR (p=0.02).

Conclusions:
Most respondents were aware of HOCPR. Those who were aware were more likely to give HOCPR to a bystander in an emergency. Likeliness to give HOCPR varies by global region. Efforts are needed in all regions to increase awareness and remove barriers that prevent people from helping OHCA victims.
Abstract 13500: Real-World Healthcare Resource Utilization Outcomes With Dronedarone versus Sotalol Following Ablation in Adults With Atrial Fibrillation
Authors: Zeitler Emily P , Stein Dara , PREBLICK RON , Kabadi Shaum M , MCKINDLEY David , Rashkin Jason , Huse Samuel , Stamas Nicole , Kim Michael H
Published: June 2023

Introduction:
Dronedarone has shown clinical benefit vs sotalol in adults with atrial fibrillation (AF) post-ablation, but healthcare resource utilization (HCRU) in this setting is unknown.

Methods:
A retrospective, observational cohort study was conducted using IBM MarketScan® data (Jan 2012-Mar 2020) in adults with AF receiving dronedarone or sotalol post-ablation. Patients needed to have 12 months of pre-ablation data; follow-up ended at earliest of health-plan disenrollment, death or end of study (Dec 2020). Prevalence (events per 100 patient-years [PY]) was calculated for all-cause and cardiovascular (CV)-related HCRU (hospitalizations; emergency room [ER] visits; outpatient office visits; other outpatient services). Patients receiving sotalol were propensity score (PS)-matched 1:1 to patients receiving dronedarone and compared by univariate generalized linear models with Poisson distribution. Time-to-event (TTE) cumulative incidences for all-cause, CV-related and atrial tachyarrhythmia (ATA)-/AF-related hospitalization, and for pacemaker insertion, were compared by Kaplan-Meier analysis and log rank test.

Results:
After PS-matching, the dronedarone and sotalol (n=1600 per cohort) cohorts were successfully matched across several criteria (mean follow-up: ~28 months; age at ablation: ~61 years; proportion male: ~70%; hypertension: ~71%; heart failure: ~13%; mean CHA2DS2-VASc score: ~1.8; mean Charlson comorbidity index: ~0.8). Post-ablation, prevalence per 100 PY of all-cause hospitalization (24.0 vs 27.4), ER visits (53.1 vs 59.5) and other outpatient services (1140.1 vs 1184.5), and of CV-related hospitalization (8.4 vs 11.3), ER visits (8.5 vs 10.0) and outpatient office visits (379.6 vs 390.9), were significantly lower with dronedarone vs sotalol. Cumulative incidences were significantly lower with dronedarone vs sotalol (
Figure
).

Conclusions:
Post-ablation dronedarone was associated with lower HCRU vs sotalol.
Abstract 13502: Prognostic Significance of Non-Infarct-Related Coronary Artery Chronic Total Occlusion in Patients Presenting With Acute Myocardial Infarction: A Systematic Review and Meta-Analysis
Authors: Ahsan Muhammad Junaid , Lateef Noman , Ahmad Soban , latif azka , Ahsan Muhammad Zoraiz , faizi kainat , Mirza Mohsin M , Tannenbaum Mark , Ardhanari Sivakumar , Goldsweig Andrew M
Published: June 2023

Introduction:
In patients with acute myocardial infraction (AMI), multivessel coronary artery disease (CAD) is associated with worse prognosis than single-vessel CAD. Several observational studies have reported worse clinical outcomes in AMI patients with non-infarct-related artery chronic total occlusion (n-IRA CTO). We performed a systematic review and meta-analysis to evaluate the prognostic significance of n-IRA CTO in patients with AMI.

Methods:
Systematic review was performed querying PubMed, Google Scholar, Cochrane and clinicaltrials.gov from Inception through May 2022. Studies comparing AMI patients with and without n-IRA CTO were included. Outcomes included in-hospital, 30-day and long-term mortality, cardiac mortality, major adverse cardiovascular events (MACE), and major bleeding. Risk ratios (RRs) and 95% confidence intervals (CIs) were calculated using random effects models.

Results:
Five prospective, eight retrospective and 3 subgroup analyses of randomized control trials (RCTs) (n-IRA CTO n=2,521, no CTO n=18,397) were identified. Presence of n-IRA CTO was associated with higher in-hospital (RR 2.86, 95% CI 1.77-4.62, p<0.0001, Figure A), 30-day (RR 2.54, 95% CI 1.66-3.89, p<0.00001, B) and long-term mortality (RR 2.32, 95% CI 1.81-2.99, p<0.00001, C), as well as increased risk for cardiac mortality (RR 2.24, 95% CI 1.79-2.81, p<0.0001, D), MACE (RR 1.51, 95% CI 1.32-1.74, p<0.0001, E), and major bleeding (RR 1.99, 1.16-3.41, p=0.01, F) when compared to AMI patients without n-IRA CTO.

Conclusions:
In AMI patients, the presence of n-IRA CTO is associated with increased mortality and morbidity. Future studies should evaluate whether intensive monitoring and specialized care can improve outcomes in these patients.
Abstract 13524: Rising Burden of Acute Cardiovascular and Cerebrovascular Events in Young Females (18-44 Years) With Cannabis Use Disorder
Authors: Sura Harsh R , Pusa Mounika , Patel Aneri , Bhanushali Aditi , Siddique Muhammad Saad , Aggarwal Sanjana , Sharma Marisha Rai , Javed Haris , DHRUVE RITIKA , Desai Rupak
Published: June 2023

Background:
With the increasing recreational use of Cannabis in the United States, there is limited data on the impact of Cannabis use on young females. Therefore, we aimed to assess the risk and outcomes of cardiovascular and cerebrovascular events in young females with Cannabis use disorder (CUD).

Method:
The National Inpatient Sample (2019) was assessed to identify young, female hospitalizations (age 18-44 years) with CUD using relevant ICD-10 codes. Baseline characteristics and comorbidities were compared between two cohorts, CUD + and CUD -. The primary outcome was acute cardiovascular and cerebrovascular events evaluated using a multivariable regression analysis adjusting for confounders.

Result:
Of 1,72,36,228 young female hospitalizations, 2% had CUD+ (n=340560). CUD+ arm consisted of younger (median age-34 vs 59), black patients (28.2vs15.5%) and had a higher rate of drug abuse (62.1% vs 3%), smoking (50.7% vs 12.4%) and alcohol abuse (13.9% vs 2.5%) when compared to CUD- cohort (p<0.001). Despite a lower prevalence of comorbidities (p<0.001) such as Hypertension, Diabetes, Hyperlipidaemia, Obesity, PVD, CKD, Prior MI, Prior PCI, Prior CABG, Prior Stroke, Prior VTE, CUD+ group showed higher odds of Type 1 MI (OR=1.11,95%CI-1.04-1.18,p=0.001), Dysrhythmia (OR=1.08,95%CI-1.05-1.11,p-<0.001), however the CUD+ cohort had lower odds of Type 2 MI(OR=0.89,95%CI-0.83-0.96,p-0.003), Cardiogenic Shock (OR=0.78,95%CI-0.7-0.87,p<0.001), Cardiac arrest including VF (OR=0.79,95%CI-0.72-0.87,p<0.001), and Acute PE (OR=0.74,95%CI-0.68-0.8,p<0.001) as compared to without CUD cohort.

Conclusion:
Despite having an overall lower CVD risk burden, the CUD+ female cohort had a higher risk of Type 1 MI and Dysrhythmia after controlling for other confounding risk factors and substance abuse. abuse.
Abstract 13530: The Impact of COVID-19 Illness Risk on Physical Activity During the Pandemic
Authors: Wierenga Kelly L , Moore Scott E , Ofner Susan , Mulkey Malissa , Alwine Jennifer , Blake Hannah , Hacker Eileen , Chang Pei-Shiun , Pressler Susan J , Perkins Susan
Published: June 2023

Introduction:
Risk related decision making for physical activity engagement changed during the pandemic. Importantly, life-threatening COVID-19 illness was riskier for adults with many chronic illnesses, including cardiovascular diseases. Determining physical activity level differences between people at high versus low risk for severe COVID-19 is critical for targeting future approaches for improving physical activity and cardiovascular health.

Hypotheses:
Between March 2020 and May 2021, compared to adults at low risk for severe COVID-19, adults at high risk have 1) greater odds of inactivity; and 2) in adults reporting physical activity, high risk is associated with lower metabolic equivalent of task (MET).

Methods:
This prospective observational study enrolled English-speaking US adults age 18 years and older.  Measures included demographic and health condition surveys, and the International Physical Activity Questionnaire (IPAQ) short form surveys at baseline, with IPAQ repeated at 3, 4, 7, 9, and 13 months. Inactivity was defined as reporting no activity bouts ≥ 10 minutes. Hypotheses testing used a two-part model of physical activity over time simultaneously fitting a logistic model of inactivity and a gamma model of total MET for the physically active while adjusting for age, gender, and race. 

Results:
The sample included n = 687 (mean age = 42.4 ± 15.5, 78% women, 89% white). Odds of inactivity for COVID-19 high risk group was 2 to 4.1 times higher than that of low risk group at baseline and 13 months (Figure 1a). Physically active adults at high risk of severe COVID-19 had MET levels less than the low risk group at baseline (28%, p = .001), 3 (29%, p = .002), and 4 months (30%, p =.005), with no significant differences at later timepoints (see Figure 1b).

Conclusions:
Inactivity and MET level between group differences varied over time. Disproportionate odds of inactivity and lower MET levels was present primarily early in the pandemic in the high risk group.
Abstract 13536: Cardiac Rehabilitation Enrollment Among Medicare Beneficiaries: Surgical Hospitals Play a Critical Role!
Authors: Pack Quinn R , Priya Aruna , Lagu Tara , Pekow Penelope , Mazor Kathleen , Ades Philip , Lindenauer Peter K
Published: June 2023

Introduction:
Hospitalization for myocardial infarction (MI), percutaneous coronary intervention (PCI), or cardiac surgery [coronary artery bypass surgery (CABG) or valve surgery] represents a key opportunity to refer and recruit eligible patients to cardiac rehabilitation (CR.) However, little is known about how hospitals influence CR enrollment at the national level.

Methods:
Using Medicare fee-for-service claims from 2017, we identified all patients with a principal discharge diagnosis of MI, PCI, CABG, or valve surgery. We defined CR enrollment as attending ≥ 1 session within 90 days and calculated hospital-specific CR enrollment rates. To assure stability of our statistical results, we limited our sample to hospitals where cardiac surgery was performed, and then examined the association between patient demographics, procedures, comorbidities, and hospital characteristics on CR enrollment using mixed effects hierarchical logistic regression. We calculated the median odds ratio (MOR) to estimate the extent to which the hospital where a patient was cared for influenced their chance of enrolling in CR.

Results:
At 3,420 hospitals, we identified a total of 264,970 eligible patients (age 77 ± 8 yrs., 58% male, 85% white, 39% surgical), of which 25% attended CR. While a minority (38%) of hospitals performed cardiac surgery - these hospitals cared for the vast majority (92%) of all eligible patients. At these hospitals, the median CR enrollment rate was low (22%) and varied 10-fold across hospitals at the 10
th
and 90
th
percentiles (3%, 42%). After multivariable adjustment, the factors most associated with CR enrollment were having cardiac surgery or undergoing PCI (OR 5.8, 2.6 vs. MI respectively), advancing age (OR 0.77 per 5-year increase), low socioeconomic status (OR 0.33), smoking (OR 0.59), or living in the Midwest (OR 2.3 vs. South), p <0.001 for all. The hospital MOR was 2.1, similar in effect size to PCI or Midwest location.

Conclusions:
In this large national study of older adults, participation rates in CR were low, and the hospital where patients receive their care was strongly associated with CR enrollment. As surgical hospitals care for the majority of all eligible patients, they appear to be the most logical place to focus improvement efforts.
Abstract 13539: The Effect of Emergency versus Delayed Coronary Angiography After Out-of-Hospital Cardiac Arrest Without ST-segment Elevation: A Meta-Analysis of Randomized Clinical Trials
Authors: Abuelazm Mohamed T , Awad Ahmed K. , Swed Sarya , Abdelazeem Basel , Baral Nischit , savarapu pramod , Santos Volgman Annabelle S
Published: June 2023

Introduction.
The prognosis of patients with out-of-hospital cardiac arrest (OHCA) is poor, with high mortality rates and poor neurological outcomes. Early coronary angiography (CAG) is recommended in patients with ST-segment elevation myocardial infarction (STEMI) associated with cardiac arrest; however, performing early or delayed CAG in patients with OHCA without STEMI is unclear. Therefore, we conducted a meta-analysis of randomized controlled trials (RCTs) to investigate the efficacy of early versus delayed CAG in patients with OHCA without STEMI.
Methods.
We searched Web of Science, SCOPUS, EMBASE, PubMed (MEDLINE), and CENTRAL from inception till June 2022. We included only RCTs that compared early versus delayed CAG in patients with OHCA. The main outcomes were percutaneous coronary intervention (PCI) rate, 30-day all-cause mortality, and neurological recovery (cerebral performance category (CPC) < 3). We used the fixed-effect model to pool the risk ratio (RR) with a 95% confidence interval (CI).
Results.
We included seven RCTs with a total of 2104 patients. The overall risk ratio showed no difference between early and delayed CAG regarding PCI rate (RR: 1.06 with 95% [0.92, 1.23] p= 0.43), 30 days mortality (RR: 1.08 with 95% CI [0.97, 1.20] p= 0.15, and neurological recovery (RR: 1.04 with 95% CI [0.95, 1.13] p= 0.4).
Conclusion.
Among patients who experience an OHCA without STEMI, a strategy of performing early CAG provided no benefits in respect to the rate of PCI, 30 days mortality, and neurological recovery compared to delayed CAG.
Abstract 13541: A Digital Health Ecosystem for Coronary Artery Bypass Graft and Percutaneous Coronary Angiography Facilitates Recovery for Patients in Their Homes
Authors: Taylor J A , Rao Jyotsna , Singerman Richard , Sharma Prem , Hsieh Christine
Published: June 2023

Introduction:
The transition from hospital to home disrupts the continuum of patient care, adversely impacting readmissions and patient engagement. Our study objective is to develop and assess a Digital Health Ecosystem (DHE) intervention to mitigate CABG and PTCA readmissions and improve patient satisfaction with minimal clinician burden.

Methods
We developed and assessed a DHE combining evidence-based personalized content; web-based clinician dashboards; patient caregiver mobile apps; and nurse care plans and escalation protocols (figure). A tertiary-care hospital in Bangalore, India deployed the DHE to address post-discharge challenges of CABG and PTCA. India is attractive for testing digital health due to its large population, large mobile phone penetration, large out of pocket healthcare costs and positive telehealth attitudes. In an IRB-approved retrospective study, Jan-Dec 2019, we assessed patient outcomes and satisfaction for 799 patients (CABG=325; PTCA=474). We used an all-comers real-world approach without exclusions to assess feasibility.

Results
Escalations of care (n=7665), were greater in CABG (n=4772; 15 per patient) compared with PTCA (n=2893; 6 per patient). The figure shows 101 higher level escalations from 82 patients (48 CABG, 34 PTCA) with 41 resolved via virtual care and 60 resulting in 35 ED visits and 17 hospitalizations. Net Promoter Score (NPS) indicated patients were loyal and likely to recommend the DHE. The hospital NPS increased by 60%, from hospital reported baseline of 47 to 75.

Conclusions
Only 10.3% of patients after discharge had serious complaints. There were relatively few ED visits (4.4% of patients) and even fewer readmissions (1.9%). This contrasts with Indian studies showing 10-20% readmission after CABG. We demonstrated a DHE that provides improved post-discharge patient care and satisfaction and can be implemented alongside traditional healthcare. Moreover, this DHE may significantly reduce readmissions.
Abstract 13549: Plasma Metabolomics Identify Major Differences in Symptoms and Quality of Life Among Patients With Heart Failure
Authors: Jurgens Corrine Y , Lee Christopher S , Faulkner Kenneth M , Lanfear David E
Published: June 2023

BACKGROUND:
Plasma metabolites predict survival among patients with heart failure (HF), but symptom burden is critical, underpinning functional status and quality of life (QOL). The relationship of plasma metabolome and symptom or QOL phenotypes is not established.

AIM:
We conducted a latent class analysis to identify plasma metabolite patterns in relation to symptoms and QOL among HF patients.

METHOD:
A prospective HF registry collected baseline plasma for metabolomics and health status. A total of 13 metabolites (organic acids, amino acids, acylcarnitines) previously shown to predict survival were used in analyses. QOL and symptoms were quantified using the Kansas City Cardiomyopathy Questionnaire. Distinct metabolite patterns were identified using latent class mixture modeling. Linear regression tested the association of metabolite profile with QOL and total symptom scores controlling for age, gender, and NYHA class. One-way ANOVA characterized group differences.

Results:
A total of 1192 patient participants had complete metabolite and health status data for analysis. Among these patients, 62% were male, 48.5% self-identified as African-American and average age was 68 years (± 12). The majority (58%) were non-ischemic, 56% were NYHA Class I and comorbid conditions were common (90% hypertension, 72% hyperlipidemia, 43% diabetes). Three metabolite latent profiles (MLPs) were identified. MLP 1 had significantly higher NT-proBNP, worse functional class (72% NYHA 3-4) and lower ejection fractions (0.30 vs 0.35) compared with MLP 2 and 3. MLP class predicted symptoms (R
2
=0.39, F(7,1182)=F 107, p=0.006) and total QOL scores (R
2
=0.31, F(7, 1182)=F77.3, p=<0.001) controlling for age, gender and NYHA class. The magnitude of difference was high; among MLP 2 and 3 compared to MLP1, total symptom scores ranged 7-9 points better and QOL 12-15 points better. No differences in age, gender or race were found across MLPs.

Conclusion:
Three latent metabolite profiles were identified that independently associated with significant differences in symptoms and QOL. Considering a minimal clinically important difference in KCCQ scores is 5 points, our results demonstrated large differences in patient reported outcomes related to plasma metabolite profile.
Abstract 13573: Machine Learning to Identify Predictors of Lapses in a Beginners’ Exercise Program for Adults With Type 1 Diabetes
Authors: Doshi Rajat , Liu Jason , Jeon Sangchoon , Businelle Michael S , Hebert Emily T , Nally Laura , Stults-Kolehmainen Matthew , Fucito Lisa , Weinzimer Stuart , Gerstein Mark , Ash Garrett , Stults-Kolehmainen Matthew
Published: June 2023

Introduction:
People with type 1 diabetes (T1D) are advised to perform the amounts of exercise recommended for the general population but encounter additional barriers including blood glucose management and fear of hypoglycemia. We previously reported that 20 adults with T1D (55% female) that received personalized biosensor feedback, completed mood diaries, and accessed on-demand instructional videos for 10 weeks increased their exercise to levels that partially met recommendations (median 64 [IQR 20, 129] minutes/week). Herein we use machine learning methods to predict the occurrence of lapses (i.e., days when exercise was not performed).

Methods:
We modeled exercise lapses using 95 possible predictive features derived from the prior 7 days of: 1) continuous glucose monitor summary statistics (mean, variability, time >180, 70-180, <70 mg/dL) for each daytime, nighttime, and 24hr window; 2) negative glycemic experiences around exercise (hypo/hyperglycemia, excessive insulin-on-board, nocturnal hypoglycemia); 3) subjective fear of hypoglycemia entered each morning and evening; 4) subjective sleep quality; and 5) illness. We created three different models using Random Forest (RF), Support Vector Machine (SVM), and Deep Neural Network (DNN) with an 80:20 train-test split of the data (960 training & 240 testing days). We used upsampling to balance the data between lapse and non-lapse days.

Results:
First, the SVM achieved 71.2% with the most important features being sickness, mean nighttime glucose levels, 24hr time <70 mg/dL, and variability. Next, the RF achieved a higher accuracy (74.1%) with the most important feature being sleep (significance 0.16) followed by the negative glycemic experiences around exercise (0.09 - 0.14). The most accurate model was the DNN with 5-fold cross-validation (75.2% accuracy, 77.5% precision, 71.4% sensitivity).

Conclusion:
Machine learning models that leverage biosensor, mood, and sleep data may be used to predict exercise lapses for adults with T1D, which could inform just-in-time motivational prompts in future mobile exercise interventions. Model performance might be improved by including subject-level features (e.g., demographics) and adding a sleep biosensor to complement sleep ratings.
Abstract 13583: Conduction System Pacing Experience: His Bundle vs. Left Bundle Branch Area Pacing at Columbia University
Authors: Lavelle Michael , Yarmohammadi Hirad , Sorbera Carmine , Ehlert Frederick , Biviano Angelo B , Garan Hasan , Wan Elaine Y
Published: June 2023

Introduction:
Conduction system pacing (CSP) with His bundle pacing (HBP) and left bundle branch area pacing (LBBAP) are utilized as alternatives to RV endocardial and biventricular pacing. Which patients gain the most benefit from CSP remains an area of active investigation.

Objective:
To report on the early experience with HBP and LBBAP conduction system pacing at an academic medical center.

Methods:
All patients with a Medtronic 3830 SelectSecure lead implanted from 3/2016 to 5/2022 at Columbia University were selected for chart review. Patients were excluded if follow up interrogation or clinical data were unavailable for review.

Results:
A total of 36 patients were included and 3 were excluded for lack of follow up. 25 patients had HBP and 11 patients had LBBAP (Table 1). Average time from implant to most recent interrogation for HBP was 530.8 ± 506.2 days, range 22 - 1589, compared to 113.6 ± 149.6 days, range 10 - 397, for LBBAP. The implant threshold was significantly higher in HBP compared to LBBAP (1.58 ± 1.06 V vs. 0.57 ± 0.19 V, p=0.004) (Table 1). There were increased threshold in both groups at follow up compared to initial implant HBP (1.81 ± 1.19 V vs 1.58 ± 1.06, p=0.17) and LLBAP (< 30 days of follow up [n=4], 0.84 ± 0.66 V vs 0.58 ± 0.22 V,p=0.46; >30 days of follow up [n = 7], 1.34 ± 1.40 vs 0.57 ± 0.19, p=0.18) although it was not significant. Complication rates were low, one HBP lead was deactivated due to high threshold, two LBBAP patients required lead revision, one for dislodgement and one for pocket infection.

Conclusions:
CSP is a feasible and safe procedure. Higher thresholds were observed in the HBP group at implant compared to the LBBAP group. There was a trend of an increased threshold over time in both groups. Ongoing monitoring of the LBBAP is crucial for long term feasibility.
Abstract 13588: Association of Longitudinal Trajectories of Branched Chain Amino Acids Through Young Adulthood With Diabetes in Later Life: The CARDIA Study
Authors: Sawicki Konrad T , Ning Hongyan , Allen Norrina B , Carnethon Mercedes R , Wallia Amisha , Otvos James D , Ben Sahra Issam , McNally Elizabeth M , Snell-Bergeon Janet , Wilkins John T
Published: June 2023

Introduction:
Branched chain amino acids (BCAA), measured at a single timepoint in midlife, are directly associated with risk for incident type 2 diabetes mellitus (DM), a strong determinant of cardiovascular disease risk. However, the trajectories (traj) of BCAAs through young adulthood and their associations with DM in midlife are unknown.

Methods:
We used NMR spectroscopy to measure serum BCAA levels from up to 3,081 Coronary Artery Risk Development in Young Adults (CARDIA) participants who attended the Year(Y) 2, 7, 15, 20, and 30 exams. We used latent class modeling to generate BCAA traj groups. To quantify associations between BCAA traj and prevalent DM* at the Y30 exam, we excluded participants with DM at Y2, and modeled traj groups from Y2 to Y30. To quantify associations between BCAA traj and incident DM by the Y30 exam, we excluded participants who developed DM by the Y20 exam and modeled traj from Y2 to Y20. We used adjusted** logistic regression to quantify the associations between traj group and prevalent and incident DM (at Y30), separately.

Results:
Among 3,081 participants (mean age at Y2: 27y), there were 3 BCAA traj groups: 1,427 participants in the low-stable group, 1,384 in the moderate-stable group, and 270 in the high-increasing group. Male sex, Black race, and higher body mass index were more common in the higher BCAA traj groups. Compared with the low-stable BCAA traj group (reference), the moderate-stable and high-increasing BCAA traj groups were associated with prevalent DM at Y30 (OR [95
th
CI]: moderate-stable, 2.59 [1.90-3.55]; high-increasing, 6.03 [3.86-9.43]). Moderate-stable and high-increasing traj groups were associated with incident DM at Y30 (OR [95
th
CI]: moderate-stable, 1.56 [1.02-2.39]; high-increasing, 2.20 [1.25-3.87]; low-stable, reference).

Conclusions:
BCAA levels track, on average, over a 28-year span in most young adults, but serial measurements identify subpopulations with rising levels and high risk of DM in later life.
Abstract 13590: The Fick Method With Lafarge Estimates of Oxygen Consumption Systematically Over-Estimates Cardiac Index When Compared to Thermodilution in Children
Authors: Lawson Andrew A , Tannous Paul , Laternser Christina , Migally Karl
Published: June 2023

Introduction:
There are known sources of error in cardiac index calculated by the Fick method with LaFarge estimates of oxygen consumption (eFick CI) and in cardiac index measured by thermodilution (TDCI). In a large adult cohort, there was only modest correlation between eFick CI and TDCI.

Hypothesis:
Among pediatric patients undergoing cardiac catheterization, eFick CI and TDCI will differ by greater than 20% in greater than 10% of cases.

Methods:
We performed a single-center retrospective chart review of patients aged 3-18yrs who underwent cardiac catheterization with documented eFick CI and TDCI from 2004 to 2020. eFick CI was calculated using oxygen consumption estimated by the LaFarge equation.

Results:
Among 201 right heart catheterizations (mean age 12.2 yrs, SD 4.4yrs; 51% male) performed on 161 distinct patients, the most frequent diagnosis was cardiomyopathy, followed by congenital heart disease, and pulmonary hypertension. TDCI and eFick differed by >20% in 49% of catheterizations; further, eFick CI was systematically higher than TDCI, with mean difference +0.71L/min/m
2
, SD 1.07L/min/m
2
. In a multivariate linear regression analysis (Table 1), higher mean CI ((eFick CI + TDCI)/2), and older age were predictive of greater percent difference between eFick CI and TDCI; for each increase in mean CI by 1.0 L/min/m
2
, the expected percent difference in CI increased by 9.9% (p=0.000).

Conclusions:
In pediatric patients undergoing cardiac catheterization, eFick CI is systematically higher than TDCI and the difference between values is frequently >20%, which may have clinically significant implications. Discrepancies between eFick CI and TDCI increase at higher mean CI.
Abstract 13592: Gender Related Divergences in Cardiac and Vascular Function With Age
Authors: Brazile Tiffany L , Macnamara James P , Carrick-Ranson Graeme , Howden Erin J , Levine Benjamin D , Sarma Satyam
Published: June 2023

Introduction:
Heart failure with preserved ejection fraction (HFpEF) is a disease of advanced aging that disproportionately affects women. Diastolic function changes with age and it is unknown if gender-related differences in progression exist. Understanding ages at which parameters of vascular and diastolic function diverge may provide insight into the differential risk of HFpEF between genders.

Methods:
Sedentary but healthy non-obese subjects aged 20-90 (n=178, 58% female; avg age 56 ± 13 yrs) underwent measures of pulmonary capillary wedge pressure (PCWP; right heart catheterization), blood pressure and cardiac output (acetylene rebreathe). Diastolic function was assessed by Doppler echocardiogram. A generalized linear model was used to estimate effects of age for each measured hemodynamic parameter as a function of gender.

Results:
Across age, women had higher systolic blood pressure (SBP) (age*gender p=0.025, age p<0.001) and total peripheral resistance (TPR) (age*gender p=0.053, age p<0.001). Changes in TPR were apparent at age 26 while SBP diverged at age 55. (Figure) Women had slower early diastolic recoil (e’) (age*gender p<0.001) starting at age 55. While E wave velocity was lower in women, age-related decline was similar to men. E/e’ was higher in women (age*gender p=0.007) and diverged at a young age (28). PCWP declined with age similarly in both men and women. Systolic velocity (s’) declined in early middle age (42) in women (age*gender p=0.007, age p=0.002).

Conclusions:
Women experience greater changes in cardiac and vascular function with age than men. The age at which these parameters diverge differs, with evidence for decline in vascular function and cardiac contractility occurring at young ages in women while changes in SBP and diastolic recoil occur after age 55. Understanding lifestyle and hormonal factors that influence these differences may help elucidate HFpEF risk factors that are modifiable and serve as a target for therapy.
Abstract 13596: Effects of Plasminogen Activator Inhibitor-1 on the Circadian Clock in Liver
Authors: Wilsbacher Lisa D , Levine Joshua A , Eren Mesut , Shang Meng , Kalousdian Anthony , Vaughan Douglas E
Published: June 2023

Introduction:
Plasminogen activator inhibitor-1 (PAI-1, encoded by
Serpine1
) plays a major role in the mammalian fibrinolytic system, but elevated PAI-1 activity contributes to other biological processes including the metabolic syndrome. Multiple studies suggest that disruption of circadian rhythms also promotes features of the metabolic syndrome including obesity, hypertension, and type 2 diabetes. While it has been long known that PAI-1 plasma levels exhibit a marked circadian variation, and that the expression of PAI-1 is strongly influenced by the clock, a reciprocal role for PAI-1 in regulating components of the clock itself has never been described.

Hypothesis:
We hypothesized that changes in PAI-1 activity influence the expression of core circadian clock genes and clock-controlled genes in the liver.

Methods:
We used two mouse models of reduced PAI-1 activity: oral PAI-1 inhibitor TM5614 (20 mg/kg/day) versus vehicle in C57BL/6J wild-type mice (n = 5 per group), and
Serpine
+/-
heterozygous mice versus wild-type littermate control mice (n = 3 per group). Mice were maintained on a 14:10 light:dark cycle. Livers were collected between 3 and 4 hours after lights-on, which corresponds to Zeitgeber Time (ZT) 3-4. RNA was isolated for RNA-seq and downstream analyses.

Results:
Between ZT 3-4, we found that reduced PAI-1 activity led to marked changes in circadian gene expression in the liver. Both PAI-1 inhibition with TM5614 and PAI-1 haploinsufficiency significantly increased expression of the core circadian clock components
Arntl
(aka
Bmal1)
and
Clock
while significantly reducing expression of core clock components
Per1, Per2, Per3,
and clock output genes. Furthermore, we found that PAI-1 inhibition in aged transgenic mice overexpressing the stable variant of human
SERPINE1
rescued two markers of impaired circadian function: 1) the premature onset of activity prior to lights-off, and 2) reduced feeding during the lights-off period.

Conclusions:
Taken together, these data support a reciprocal role for PAI-1 in regulating components of the circadian clock. Elevated PAI-1 activity may contribute to the metabolic syndrome through effects on the circadian clock and may provide a mechanistic link between PAI-1, the circadian clock, and aging.
Abstract 13600: Performance of a Multi-Metabolite Score Added to a Risk Prediction Model for Incident Diabetes in Young Adults: The CARDIA Study
Authors: Sawicki Konrad T , Ning Hongyan , Fine Keenan , Allen Norrina B , Carnethon Mercedes R , Otvos James D , Shah Ravi V , Murthy Venkatesh L , Wilkins John T
Published: June 2023

Introduction:
The Finnish Diabetes Risk Score (FINDRISC) is a risk prediction tool used to estimate absolute risk for type 2 diabetes mellitus (DM), a critical risk factor for cardiovascular disease. The Diabetes Risk Index (DRI) is a multi-metabolite DM risk score developed by combining the Lipoprotein Insulin Resistance Index (LP-IR), calculated from six lipoproteins, and the branched chain amino acids, valine and leucine. Although the DRI is independently associated with future DM in middle-aged adults, the performance of this novel biomarker when added to FINDRISC to predict incident DM in young adults is not known.

Hypothesis:
The addition of DRI to FINDRISC will improve the 10-year(y) risk prediction of DM across all ages in the Coronary Artery Risk Development in Young Adults (CARDIA) study.

Methods:
We measured the DRI using NMR spectroscopy in CARDIA participants across different age categories: 20-30y (n=1,911), 30-40y (n=2,716), 40-50y (n=2,232). We used Cox proportional hazards regression to evaluate the association of the DRI with incident 10-y DM risk. We assessed FINDRISC model performance using C-statistic and continuous Net Reclassification Index (NRI) with and without the addition of the DRI as a covariate.

Results:
DRI was associated with 10-y DM risk across all age categories. Addition of the DRI modestly improved the C-statistic in the 30-40-y age category. Addition of DRI to FINDRISC improved the overall NRI in the 30-40- and 40-50-y age categories. The non-event NRI was significant across all 3 age categories and reclassified 25-36% of participants who did not develop DM to a lower estimate of incident DM risk (Table).

Conclusions:
Among young and middle-aged adults, DRI scores were associated with 10-y risk of DM. The addition of DRI to FINDRISC led to improvements in reclassification of DM risk, as the addition of DRI to FINDRISC correctly classified up to 36% of participants who did not develop DM (over 10y) to a lower estimate of incident DM risk.
Abstract 13601: An Evidence-Based Population Screening Strategy for
TTN
: Statistical Analysis of Over 450,000 Clinicogeomic Records Reveals High Prevalence of Cardiomyopathy in Carriers of Cardiac
TTN
tvs With Atrial Fibrillation
Authors: Schiabor Barrett Kelly M , Cirulli Elizabeth T , Bolze Alexandre , Rowan Chris , Elhanan Gai , Grzymski Joseph J , Lee William , Washington Nicole L
Published: June 2023

Introduction:
Truncating variants in
TTN
(
TTN
tvs) are the largest genetic cause of dilated cardiomyopathies (DCM). In populations, genetic variation in
TTN
is pervasive and penetrance estimates for DCM are low, even when carriers are limited to those with
TTN
tvs in exons with “percentage spliced in” index > 90 (hiPSI), a representation of constitutive cardiac expression. Patients with cardiomyopathies (CM) often carry a large number of other cardiac conditions, such as atrial fibrillation (Afib). We sought to confirm this association and determine whether the presence of Afib and a hiPSI
TTN
tv predicted CM.

Results:
Leveraging clinicogenomic data from ~450,000 individuals in two health systems, we show support for associations with both CM and Afib at the population level. We perform a sliding window analysis of
TTN
tvs and confirm the association is specific to hiPSI exons, with no meaningful associations in exons with less cardio expression. The combination of hiPSI
TTN
tv carrier status and early Afib diagnosis (dx before age 60) finds a subset of
TTN
carriers at high risk for CM (34% prevalence) - this risk is 3.5 fold higher than that of all hiPSI
TTN
tv carriers (9% prevalence) and 5-fold higher than non-carriers with early Afib (5% prevalence, p=4.8e-56 after controlling for age and sex). Further, Afib either predates or is concurrently diagnosed with CM in 72% of those with both diagnoses.

Conclusion:
CM and Afib are linked in hiPSI
TTN
tv carriers and may represent progressive manifestations of structurally-based heart failure. Our retrospective analysis suggests hiPSI
TTN
tv screening (~0.5% of cohorts) in conjunction with routine monitoring for arrhythmias may be an effective strategy to improve outcomes and reduce the incidence of severe cardio outcomes in the population.
Abstract 13610: Imbalance Between GCN5L1 Mediated CypD Acetylation and Sirt3 Deacetylase Promotes Mitochondrial Oxidative Stress, Endothelial Dysfunction and Hypertension
Authors: Dikalov Sergey , Tkachuk Liliya , Ao Mingfang , Fehrenbach Daniel , Sack Michael , Dikalova Anna
Published: June 2023

Nearly half of adult population has hypertension which is a main risk factor for cardiovascular disease. Mitochondrial dysfunction contributes to hypertension and targeting mitochondria can potentially improve treatment of hypertension. We found hyperacetylation of mitochondrial Cyclophilin D (CypD) in essential hypertension and proposed that CypD acetylation can promote endothelial dysfunction and hypertension. CypD acetylation is mediated by general control of amino acid synthesis 5 like 1 (GCN5L1) protein which is counteracted by deacetylase Sirt3. We tested potential role GCN5L1 and Sirt3 in endothelial dysfunction and hypertension. Western blot of aortic mitochondria showed an increased GCN5L1 level in hypertensive mice coupled with the reduction of Sirt3 deacetylase resulting in 250% increase in GCN5L1/Sirt3 ratio promoting CypD acetylation. We reported pathogenic role of lipid oxidation products isolevuglandins (isoLGs) and scavenging isoLGs by mitochondria-targeted mito2HOBA reduces mitochondrial acetylation. We tested if mitochondrial isoLGs contributes to acetylase/deacetylase imbalance driving CypD acetylation. Treatment with mito2HOBA improves Sirt3 expression and reduces GCN5L1 level resulting in normalization of GCN5L1/Sirt3 ratio and reduced CypD acetylation. To define the pathophysiological role of GCN5L1 in endothelial cells we tested if GCN5L1 depletion prevents cytokine-induced of mitochondrial oxidative stress. Indeed, treatment of human aortic endothelial cells with AngII+TNFα induces mitochondrial O
2
.
-, however, GCN5L1 depletion using siRNA completely abrogated the cytokine-induced mitochondrial oxidative stress. To define the role GNC5L1 in pathogenesis of endothelial dysfunction we developed new tamoxifen-inducible endothelial specific GNC5L1 knockout mice (Ec
GNC5L1KO
). Depletion of endothelial GCN5L1 reduces vascular mitochondrial O
2
.
-, prevents inactivation of endothelial nitric oxide and preserves endothelial dependent relaxation in angiotensin II-infused Ec
GNC5L1KO
mice compared with wild-type littermates. These data support the pathogenic role of GNC5L1 in CypD acetylation and endothelial dysfunction and targeting GNC5L1 can be beneficial in cardiovascular disease.
Abstract 13621: Genetic and Pharmacological Induction of Endothelial Sirt3 After Onset of Hypertension Rescues Endothelial Function
Authors: Dikalova Anna , Tkachuk Liliya , Ao Mingfang , Fehrenbach Daniel , Arbiser Jack , Dikalov Sergey
Published: June 2023

Endothelial dysfunction plays critical role in the pathogenesis of hypertension and atherosclerosis. These pathological conditions are main risk factors for cardiovascular disease killing 700,000 people every year in US alone. We discovered a new control point with the potential to address this problem. We have shown that Sirt3 level is reduced in essential hypertension and endothelial Sirt3 overexpression attenuates endothelial dysfunction and hypertension. We proposed induction of endothelial Sirt3 after onset of hypertension to rescue endothelial function and reduce hypertension. To test the hypothesis, we used genetic- and pharmacological Sirt3 activation. To genetically induce the expression of endothelial Sirt3 we used Sirt3
flox/flox
mice crossed with VeCad-Cre mice treated with low dose of 4-hydroxytamoxifen (4HOT, i.p. 0.3 mg/20 g daily, 5 days) which does not have off-target cardiovascular effects. Mice underwent telemetry placement and ten days later received 4-week osmotic pumps containing vehicle (saline) or angiotensin II (0.7 mg/kg/day). 14-days later half of mice received 4HOT to induce endothelial Sirt3 overexpression. Treatment of mice with 4HOT after onset of hypertension slightly reduced blood pressure but most importantly rescued endothelial-dependent relaxation, normalized mitochondrial O
2
.
- and restored endothelial nitric oxide. Second, we tested if pharmacological induction of Sirt3 by hexafluoro (i.p. 8 mg/kg, 4 days) after onset of angiotensin II-induced hypertension improves endothelial function and reduces hypertension. It was found that hexafluoro substantially reduced systolic blood pressure, significantly diminished vascular mitochondrial O
2
.
- and improved endothelial nitric oxide. To test the role of endothelial Sirt3 in pharmacological effect of hexafluoro we used endothelial specific Sirt3 knockout mice and angiotensin II model of hypertension. Interestingly, hexafluoro was not effective in endothelial Sirt3 deficient mice supporting specific role of endothelial Sirt3. These studies demonstrate therapeutic potential of genetic and pharmacological endothelial Sirt3 induction after onset of hypertension for treatment of endothelial dysfunction diminishing cardiovascular disease.