bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 15223: Clinical and Economic Impact of Patient Loss-to-Follow-Up After Short-Term Cardiac Monitor Usage in Cryptogenic Stroke
Authors: Witte Klaus K , Rosemas Sarah C , Neisen Karah , Ziegler Paul D
Published: December 2023

Introduction:
Short-term cardiac monitors (STMs) are increasingly used in the work-up of cryptogenic stroke patients before proceeding to long-term continuous monitoring for atrial fibrillation (AF) with insertable cardiac monitors (ICM). However, the rate of ICM placement after STM is only 4-5% based on large real-world studies. The impact of patient fall-out after STM on clinical/economic outcomes is unknown.

Research Question:
The objective of this analysis was to project the risk of additional ischemic strokes and stroke-related costs with varying rates of patient loss to follow-up (LTFU) after 48-hour, 14-day or 30-day monitors, compared to an approach of continuous ICM monitoring post-stroke.

Methods:
A previously published Markov model based on the CRYSTAL-AF trial was utilized to project lifetime ischemic strokes after various monitoring strategies, from a US payer perspective. Patient characteristics and AF detection rates were based on CRYSTAL-AF: diagnostic yield with the initial STMs were 0.8% for 48-hr, 3.1% for 14-day and 6.8% for 30-day monitors. AF detection resulted in a change from aspirin to DOAC, with subsequent risks of ischemic strokes and associated costs (including acute + post-acute care) modeled based on published literature.

Results:
Increasing rates of patient LTFU after STM were associated with higher projected additional secondary strokes compared to an immediate ICM approach, across all 3 STM types (figure). In the scenario based on real-world data (95% LTFU), a range of 62-68 additional strokes are projected per 1,000 patients, with associated stroke costs of $4,928-$5,449/patient when averaged across the population.

Conclusions:
Loss of patient follow-up after STM in real-world CS patients is projected to lead to substantial secondary stroke burden due to undetected AF, compared to continuous monitoring with ICM. Future work could focus on optimizing stroke pathways to ensure timely and continued access to monitoring.
Abstract 15242: The Flipside of Flecainide: A Case of Flecainide Induced Loss of Capture
Authors: Hashmath Zeba , Samaan Sara , Naniwadekar Aditi
Published: December 2023

Introduction:
Flecainide is a class 1c anti-arrhythmic agent that slows phase 0 of the fast inward sodium (Na) channels in a rate-dependent fashion leading to decreased conduction velocity in the His-Purkinje and ventricular myocardium. Its high affinity and slow unbinding prolong QRS duration on electrocardiogram (EKG). Partial renal excretion and a narrow therapeutic index of 0.2-1mcg/mL can cause drug toxicity.

Case:
A 72-year-old woman presented with palpitations and weakness. She had a history of non-ischemic cardiomyopathy, biventricular (BiV) implantable cardioverter defibrillator, frequent premature ventricular contractions on flecainide 100 mg twice a day, and chronic kidney disease. She was hypotensive and with acute kidney injury. EKG showed wide complex ventricular rhythm, QRS duration of 305 ms and intermittent ventricular pacing (Fig.1A), changed since EKG 6 months ago (Fig.1B). Device interrogation revealed normal sensing and impedances but failure to capture from all 3 leads. She had stable lead parameters and appropriate BiV pacing 6 months ago. Chest X ray showed stable lead positions. Flecainide toxicity was suspected, and Na bicarbonate infusion was started. Flecainide level was 2.4mcg/mL (normal <1mcg/mL). She went into an idioventricular rhythm which terminated spontaneously (Fig.1C). After 48 hours of Na bicarbonate infusion, lead capture was noted with narrower QRS (198 ms) (Fig.1D) and on day 6, EKG was back to effective BiV pacing with QRS duration 127 ms (Fig.1E).

Discussion:
This case highlights the EKG manifestations of flecainide toxicity including QRS widening, sine-wave pattern and loss of pacing capture due to prolonged ventricular refractoriness. It also underscores the reversibility of this condition with prompt treatment using Na bicarbonate.

Conclusion:
Early recognition and rapid treatment of the cardiac effects of flecainide toxicity is critical in managing a life threatening but reversible medical condition.
Abstract 15244: Synchronous Care in Cardiovascular Disease: The DECIDE-CV Clinic Program
Authors: Marques Pedro , Emami Anahita , Alaamiri Abdulkhaliq , Ho Daniel , Tsoukas Michael A , Mavrakanas Thomas A , Sharma Abhinav
Published: December 2023

Background:
The care model for type 2 diabetes (T2D) and its main complications is thought to be “asynchronous” and associated with delays in care and low use of guideline-directed medical therapies (GDMT).

Hypothesis:
A synchronous care clinic for T2D patients, including a simultaneous evaluation by cardiology/endocrinology and nephrology, will enhance the rate of GDMT use and improve biomarkers of interest.

Methods:
Retrospectively analysis from patients evaluated in the DECIDE-CV clinic, a cardiometabolic clinic for T2D patients with either atherosclerotic cardiovascular disease, heart fialure (HF) or chronic kidney disease (CKD). Baseline data was compared to the data obtained in the last available visit. For patients with only one visit, the treatment prescribed at the end of the first visit was considered in the last visit group. Categorical data is presented as frequencies (proportions) and was analyzed using McNemar test. Continuous data is presented as mean±SD or median (IQR) as appropriate and was compared using the t-test for paired data or Wilcoxon test.

Results:
150 patients, 72% male with a mean age of 67±12 years. 115 (78%) had atherosclerotic cardiovascular disease, 98 (65%) had HF and 77 (51%) CKD. Comparing baseline to last visit data, there was a statistically significant increase in GDMT and de-escalation of insulin, sulfonylureas and DPP4i (Table). For patients with two sets of available laboratory data, there was a significant decrease in N-terminal pro B-type natriuretic peptide (504 [155-1160] pg/mL
vs
335 [150-1031] pg/mL, p=0.03) and albuminuria (57 [19-259] mg/g
vs
57 [9-155] mg/g, p<0.01).

Conclusion:
A synchronous care clinic for T2D patients is associated with increased use of GDMT, de-escalation of therapy that lack morbidity/mortality benefit, and improvement in prognostic biomarkers. These results can potentially translate into better outcomes in this population.
Abstract 15300: Short-Term Outcomes in Different Revascularization for Acute Coronary Syndrome With Cardiogenic Shock Supported by Impella -Report From Japanese Registry for Percutaneous Ventricular Assist Device (J-PVAD Registry)
Authors: Fujii Masahiko , Sakata Tomoki , Okino Shinichi , Mogi Kenji , Sakurai Manabu , Takahara Yoshiharu , Investigator J-PVAD
Published: December 2023

Introduction and Hypothesis:
Percutaneous coronary intervention (PCI) has tended to be selected for the treatment of acute coronary syndrome with cardiogenic shock because of its ability of earlier and less-invasive therapy, though coronary artery bypass grafting (CABG) can perform complete revascularization. We hypothesized that Impella® support has the potential to make surgical treatment much safer because Impella® can improve hemodynamic state and could have the possibility to mitigate myocardial ischemia by unloading the left ventricle.

Methods:
The aim of study is to investigate if surgical revascularization is safe and effective treatment by comparing short-term outcome with different revascularization including PCI, CABG, and hybrid therapy (PCI followed by CABG). Of 1102 cardiogenic shock cases with Impella (994 cases in PCI, 48 cases in CABG, and 63 cases in Hybrid therapy) between February 2020 and December 2021 enrolled in the J-PVAD registry, short-term outcomes were compared between 62 propensity-matched cases between PCI (n=31) and CABG (n=31), as well as 68 matched cases between PCI (n=34) and hybrid therapy (n=34).

Results:
There was no difference in all-cause mortality between the PCI and CABG group as well as PCI and hybrid therapy group. The PCI group had a greater number of NYHA class≦2 at discharge than the CABG group (17 (54.8%) in the PCI group vs 10 (32.2%) in the CABG group, p=0.012). There was no difference in the number of NYHA class≦2 at discharge between the PCI and hybrid therapy group (18 (52.9%) in the PCI group vs 15 (44.1%) in the hybrid therapy group, p=0.12).

Conclusions:
CABG and hybrid therapy showed acceptable short-term outcome compared to PCI.
Abstract 15308: NLRP3 Activation and Calcium-Dependent Contractile Function in Rat Right Ventricle Cardiomyocytes (RVCMs) Are Sexually Dimorphic and Controlled by 17β-Estradiol-via Estrogen Receptor-α
Authors: Sobrano Fais Rafael , Hoffer Christopher , Moreno Vinasco Liliana , Walts Avram , Cook Todd , Fisher Amanda , Frump Andrea L , Woulfe KC , Lahm Tim
Published: December 2023

Introduction:
NLRP3 inflammasome activation promotes right ventricle (RV) contractile dysfunction in pulmonary hypertension (PH). However, the role of NLRP3 signaling in RVCMs has not been studied. 17β-estradiol (E2) improves RVCM function in PH.

Hypothesis:
E2, via estrogen receptor-α (ERα), prevents RVCM NLRP3 inflammasome activation and contractile dysfunction in experimental PH.

Methods:
RV failure in male and female Sprague Dawley rats were induced with monocrotaline (MCT). Co-localization of NLRP3 and its partner ASC was assessed. RVCMs isolated from healthy male or female wildtype (WT) or ERα loss of function mutant (ERα
mut
) rats were treated with NLRP3 activators lipopolysaccharide (LPS 1 μg/mL, 4 h) and ATP (2 mM, 10 min) ± E2 (1 nM, 24 h) or NLRP3 inhibitor MCC950 (1 μM, 30 min). RVCM contractility and Ca
2+
levels were evaluated via IONOPTIX system. Protein levels of NLRP3 and its targets were assessed. ERα binding to the NLRP3 promoter was assessed by immunoprecipitation. RNA-seq was performed in RV tissues from male and intact or ovariectomized female rats with RV failure.

Results:
RNA-seq demonstrated that transcripts involved in NLRP3 activation are E2-regulated. RVCMs from male, but not female, MCT rats showed increased NLRP3 and ASC co-localization/activation (p<0.05). In addition, male MCT rats RVs exhibited increased activation of NLRP3 downstream mediators caspase-1 and IL-1β (p<0.05). Cultured male RVCMs treated with LPS+ATP demonstrated more pronounced NLRP3 activation and decreased contractility and Ca
2+
levels than female RVCMs (p<0.05). NLRP3 activation in RVCMs from male rats resulted in reduced contractility; this was abolished with NLRP3 inhibition (p<0.05). E2 treatment in male RVCMs reduced NLRP3 and ASC interaction and increased contractility Ca
2+
levels in male WT but not in ERα
mut
RVCMs (p<0.05). IP demonstrated ERα binding to the NLRP3 promoter.

Conclusion:
NLRP3 signaling in RVCMs from MCT-PH rats is sexually dimorphic, with more pronounced activation and contractile dysfunction in males. E2 prevents RVCM NLRP3 activation and contractile dysfunction in an ERα-dependent manner, likely mediated by ERα binding to the NLRP3 promoter. NLRP3 activation may be therapeutically targetable in PH patients of either sex.
Abstract 15332: Obesity is Associated With Acute Kidney Injury in STEMI Undergoing PCI: A National Representative Cohort Study
Authors: Ye Congyan , CONG Guangzhi , JIA Shaobin , Ma Xueping , Yan Ru
Published: December 2023

Background:
Acute kidney injury (AKI) is a frequent and serious complication after percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI). However, the relationship between obesity and the risk of AKI in this specific patient population has not been previously examined.

Methods:
We conducted a retrospective analysis of adult discharges from the National Inpatient Sample (NIS) between 2016 and 2019. ICD-10 codes were used to identify patients with STEMI who undergoing PCI. All patients were further sub-categorized into obese and non-obese cohorts. The primary outcome was the incidence of AKI. Multivariable regression models adjusting for demographics, hospital characteristics, and co-morbidities were used to examine differences in AKI incidence in the two groups of patients. Subgroup analysis and interaction tests were used to test whether this relationship was stable across groups.

Results:
A total of 62,599(weighted national estimate of 529,106) patients were included in the study, out of which 9.80% (n=6137) had AKI. Obese comprised 19.78% (n=1214) of the AKI cohort. Obese patients were on average younger, male, white race and had more comorbidities. There was a significant positive association between obesity and the incidence of AKI (aOR 1.20, 95% CI 1.10-1.31). This significant positive association was more pronounced in female patients (aOR 1.49, 95% CI 1.25-1.79, p<0.001, P-interaction=0.014). The incidence of AKI in STEMI patients after PCI increased steadily during the 4-year study period, and the adjusted trend showed that the incidence of AKI in obese patients was consistently higher than in non-obese patients.

Conclusions:
Obesity was independently associated with a greater risk for acute kidney injury among adults with STEMI undergoing PCI, especially in female patients. Further studies examining management strategies and best practices in obese patients with STEMI are warranted.
Abstract 15341: A Prospective Study on the Safety and Effectiveness of Apixaban for the Prevention of Thromboembolism in Adults With Congenital Heart Disease and Atrial Arrhythmias: The PROTECT-AR Study
Authors: Kartas Anastasios , Papazoglou Andreas , Moysidis Dimitrios , Despotopoulos Stefanos , Kosmidis Diamantis , Baroutidou Amalia , Koutsakis Athanasios , Liori Sotiria , Apostolopoulou Sotiria , Frogoudaki Alexandra , Tzifa Afrodite , Galatas Apostolos , ALEXANDRIDIS GEORGIOS , Spyridonidis Efstathios , Doundoulakis Ioannis , KARAGIANNIDIS EFSTRATIOS , Karvounis Charalampos I , Ziakas Antonios , Giannakoulas George
Published: December 2023

Introduction:
In adults with congenital heart disease (ACHD), atrial arrhythmias (AA) confer an increased risk of thromboembolic events. Limited data exist on non-vitamin K oral anticoagulant (NOAC) treatment for ACHD. We aimed to assess the effectiveness and safety of apixaban in ACHD patients with AA.

Methods:
PROTECT-AR (NCT03854149) was a prospective, multicenter, observational study conducted from 2019 to 2023. ACHD patients with atrial fibrillation, atrial flutter, or intra-atrial re-entrant tachycardia, who were routinely treated with apixaban, were included. The primary efficacy endpoint was the composite of stroke or thromboembolism. The primary safety endpoint was major bleeding. Patients who were previously on vitamin K antagonists (VKAs) before transitioning to apixaban served as a historical control group.

Results:
In total, 218 patients with ACHD and AA on apixaban (previous VKA users 34.9%) were included (mean age 51±17 years; 45.9% male; predominantly moderate complexity). Over a mean follow-up of 2.4±1.3 years, the rate of stroke or thromboembolism was 0.57% [95% confidence interval (CI): 0.15-1.55] and the rate of major bleeding was 1.52% [95%CI: 0.71-2.88] per patient-year, respectively. In the subset of patients who were previously on VKA, the risk of the primary endpoints did not differ significantly between apixaban and VKA-treatment periods (Figure).

Conclusion
In ACHD patients with AA on routine apixaban treatment, the risk of major thromboembolic and bleeding events was low. Among prior VKA users, the risk of adverse events during the apixaban-treatment period was comparable to that during the VKA-treatment period. Prospective studies directly comparing NOAC and VKA-treated patients are needed.
Abstract 15342: Outcomes of High-Intensity Interval Training Are Superior to Moderate Exercise Training Among Post-Heart Transplant Patients
Authors: Sulague Ralf Martz , CORONEL MARIA-KASSANDRA , Alfonso Pia Gabrielle , Cartojano Thea Danielle , Cruz Nikki , MORTALLA EDWARD DANIEL , LAVIE Carl J
Published: December 2023

INTRODUCTION:
Heart failure patients who underwent heart transplantation (Htx) need to undergo cardiac rehabilitation (CR) to regain and improve their physical ability and functional capacity. To date, there is no established exercise regimen that optimizes this recovery. This study aims to compare the outcomes of High-Intensity Interval Training (HIIT) versus Moderate Exercise Training (MT) among Htx patients.

Hypothesis:
The outcomes of HIIT are superior to MT among Htx patients.

Methods:
A systematic review was conducted in multiple databases including PubMed, Embase, and Google Scholar from inception to 2022 following the PRISMA guidelines to look for randomized controlled trials that directly compare clinical outcomes of HIIT versus MT. Joanna Briggs Institute (JBI) critical assessment tool was used to assess the risk of bias. A meta-analysis was performed using a random effect model to calculate mean differences with 95% confidence intervals (CI). This study is registered on Prospero (CRD42023403954).

Results:
This study included four clinical trials (n=177 patients). The average age was 51 years ± 10.57, with a majority male (73%). On average, patients were overweight (BMI = 25.78 ± 4.08) with comorbidities including hypertension (81%) and diabetes (12%). Compared to baseline levels, the peak oxygen consumption (VO2 peak), maximal muscle strength extensors, maximal muscle endurance, body mass index, and FEV1 were statistically significantly increased after the intervention of either HIIT or MT. Of these, HIIT had higher percent changes in VO2 peak at 0.205 (95% CI: 0.007 to 0.417, p=0.0578), maximal muscle strength extensors at 0.100 (95% CI: 0.059 to 0.141, p<0.001), and maximal muscle endurance at 0.263 (95% CI: 0.185 to 0.341, p<0.001) compared to MT.

CONCLUSION:
Both exercise CR regimens significantly improved the physical ability and functional performance of Htx patients. However, HIIT was superior to MT in terms of VO2 peak, maximal muscle strength extensors, and maximal muscle endurance, which may be associated with higher survival.
Abstract 15392: Performance of a Novel Unshielded Magnetocardiography Device in a First-in-Human Study
Authors: Lu Frances , Cortez Justin , Ku Jason , Iwata Geoffrey Z , Pratt Ethan J , Au-Yeung Kit Yee , Watt Clifton
Published: December 2023

Background:
Magnetocardiography (MCG) is a non-contact measurement of magnetic fields generated by the heart’s electrical currents, represented by Magnetic Field Maps (MFMs). It is effective in detecting coronary ischemia and NSTEMI. Despite the advantages of MCG, adoption has been limited due to poor usability and high costs. We designed and built a novel bedside MCG device that measures cardiac magnetic fields without the limitations of magnetic shielding or cryogenics, and tested the performance of this prototype at a hospital in a first-in-human study.

Objective:
We aimed to characterize the safety and technical feasibility of the device, prominence of cardiac features in the average waveforms, and evaluate background interference rejection.

Methods:
We enrolled 26 participants (73% Age >=55, 54% Male, 85% White) at intermediate to high risk for CAD scheduled for cardiac testing (ECG, stress test, CTA, or cardiac catheterization) as part of standard clinical care at an urban hospital. On the day of testing, all participants received a 15-minute MCG scan and a reference 12-lead ECG simultaneously. Participants were contacted 7 days later for a safety assessment. Study staff were trained for 1 hour on device operation.

Results:
Of the 26 MCG scans, 23 (88%) showed cardiac features such as QRS complex and T-waves. The average signal-to-noise ratio (SNR) of the QRS complex was 11 (SD = 6), and the average T-wave SNR was 3.6 (SD = 2). The device effectively rejected background interference >1000x larger than cardiac signals. No adverse device effects were reported.

Conclusions:
The device successfully captured cardiac signals in a magnetically noisy hospital environment. The SNR level indicates the device has the potential to generate MFMs with future capability of classifying disease states. The device’s non-contact operation, quick set-up, and bedside ease of use enables wider adoption of MCG in the clinic.
Abstract 15420: Cost-Effectiveness of Sacubitril-Valsartan in Patients With Heart Failure With Mildly Reduced or Preserved Ejection Fraction With a Recent Worsening Heart Failure Event
Authors: Dixit Neal , Truong Katie , Ziaeian Boback , Fonarow Gregg C
Published: December 2023

Background:
In a pooled analysis of the PARAGON-HF and PARAGLIDE-HF trials, sacubitril-valsartan was effective in the treatment of heart failure with mildly reduced or preserved ejection fraction (HFmrEF/HFpEF) in patients who experienced a recent worsening heart failure event.

Research Question:
The cost-effectiveness of sacubitril-valsartan in this patient population has yet to be established.
Aim:
We performed a cost-effectiveness analysis of sacubitril-valsartan in patients with HFmrEF/HFpEF in patients with a recent worsening heart failure event.

Methods:
Using a 2-state Markov model, we simulated treatment with sacubitril-valsartan vs. placebo in populations of 1,000 patients with HFmrEF/HFpEF and a recent worsening heart failure event. Clinical event rates were based on 5-year data from the I-PRESERVE trial and calibrated to reproduce event rates observed in the pooled analysis of the PARAGON-HF and PARAGLIDE-HF trials. Based on a United States health care system perspective, outcome data from the trials were used to calculate incremental cost-effectiveness ratios.

Results:
Treatment with sacubitril-valsartan resulted in an increase of 0.88 and 0.53 life years and quality-adjusted life years, respectively, compared to placebo. Lifetime costs increased due to the cost of sacubitril-valsartan. The incremental cost-effectiveness ratio was $96,762 (Table 1).

Conclusions:
Use of sacubitril-valsartan in patients HFmrEF/HFpEF with a recent worsening heart failure event displayed intermediate value by American Heart Association/American College of Cardiology standards. This study supports the current guideline recommendation to consider sacubitril-valsartan in HFmrEF/HFpEF.
Abstract 15424: Phase-to-Phase Short Phenomenon in a Left Ventricular Assist Device: Navigating Through Clinical and Ethical Challenges
Authors: Benites Moya Cesar J , Apple Sam J , Mehta Adhya , mathai sheetal vasundara , Barzallo Zeas Diego , Murthy Sandhya
Published: December 2023

Description of Case
A 59-year-old male with an axial continuous-flow left ventricular assist device (CF-LVAD) presented asymptomatically after noticing low-flow alarms. He reported extensive external driveline damage that accumulated over one year. The CF-LVAD was connected to an ungrounded cable and the driveline was repaired by the manufacturer. However, low-flow alarms continued. Log files revealed pump stoppages on all modes of power which was compatible with phase-to-phase short phenomenon (PtPSP). The patient was cannulated in case of emergent need for ECMO and upgraded to UNOS status 1 for heart transplant. Because PtPSP was considered unrepairable, the patient underwent emergent cardiac transplantation.

Discussion
The CF-LVAD driveline consists of three phases, each of which is formed by two electrical wires, connected to six motor stators. PtPSP causes driveline dysfunction due to a loss of insulation between the three phases owing to multiple breaches of the insulator, causing the pump to lose power when the damaged phases come into contact. Pump stoppages are likely and unpredictable even on batteries or an ungrounded cable. Patients may notice alarms associated with low flow, pump speed drops, or pump arrest. PtPSP is unrepairable, and pump exchange or urgent heart transplantation are the only viable treatment options.This case highlights the ethical complexity of the care of patients with advanced heart failure, whereby subjective treatment decisions often translate to objectively different levels of priority on the heart transplantation waiting list without intrinsic measures of disease severity, which may incentivize more aggressive care.

Conclusions:
CF-LVAD driveline dysfunction due to PtPSP is a clinically asymptomatic ominous scenario often uncovered by pump-controller alarms. Given the high risk of abrupt pump stoppage, a diagnosis of PtPSP necessitates emergent device exchange or explant with an orthotopic heart transplantation.
Abstract 15426: Stress-Induced Transcriptomic Shift in Human iPSC-Derived Cardiomyocytes Carrying Hypertrophic Cardiomyopathy Associated MYH7 G256E Mutation
Authors: Heinrich Paul , Lee Soah , Vander Roest Alison S , Roberts Brock , Bernstein Daniel , Wu Sean M
Published: December 2023

Introduction:
Hypertrophic cardiomyopathy (HCM) is a monogenic disorder caused by heterozygous (HET) mutations in sarcomere genes such as MYH7. Recently, human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) carrying HET HCM mutations have shed new insights into the molecular mechanisms of HCM. However, it remains unclear whether the cellular phenotypes of low penetrant mutations such as MYH7 G256E and others, can be adequately elucidated.

Hypothesis:
We hypothesize that the incorporation of cellular stressors can enhance the manifestation of pathogenic HCM phenotypes in low penetrant MYH7 mutations.

Methods:
We generated HET and homozygous (HOM) hiPSC-lines for mutation G256E in the MYH7 locus, which is associated with HCM. We performed single-cell RNA sequencing (scRNAseq) with CellPlex technology on wildtype (WT), HET, and HOM iPSC-CMs at day 30 and 60 of cardiac differentiation to establish baseline cellular transcriptional phenotype. We then treated day 30 hiPSC-CMs with 1μM isoproterenol treatment for 5 days or glucose starvation for 10 days and performed scRNAseq to assess their transcriptional shift. Additional Digital Droplet PCR studies were performed to investigate the MYH7 mutant allele expression.

Results:
In day 30 iPSC-CMs we detected a large clone-to-clone and batch-to-batch variability transcriptionally that obscured the identification of a consistent mutant phenotype in HET MYH G256E vs WT hiPSC lines. These phenotypes correlated with a 1:1 ratio of mutant vs WT allele expression. Implementation of long-term culture or treatment with isoproterenol or glucose starvation led to enhanced hypertrophic and oxidative phosphorylation gene expression in HET hiPSC-CMs. Intriguingly, the expression of MYH6 increased in MYH7-mutant hiPSC-CMs.

Conclusions:
The application of cellular stressors can enhance the manifestation of hypertrophic phenotypes in HET MYH G256E hiPSC-CMs and suggests a potential mechanism for the variable penetrance of MYH7 mutations in HCM patients.
Abstract 15445: Extracorporeal Membrane Oxygenation and Reperfusion Strategies in High-Risk Pulmonary Embolism Hospitalizations
Authors: Farmakis Ioannis T , Sagoschen Ingo , Barco Stefano , Keller Karsten , Valerio Luca , Wild Johannes , Giannakoulas George , Piazza Gregory , Hobohm Lukas , Konstantinides Stavros V
Published: December 2023

Introduction:
Extracorporeal membrane oxygenation (ECMO) offers potentially life-saving circulatory support in patients with high-risk pulmonary embolism (PE) and refractory hemodynamic instability. Optimal reperfusion strategies in combination are unclear.

Hypothesis:
To investigate the contemporary use of ECMO in conjunction with reperfusion strategies in high-risk PE.

Methods:
We identified high-risk PE hospitalizations in the Nationwide Inpatient Sample (years 2016-2020) and investigated the use of ECMO in conjunction with thrombolysis-based (systemic thrombolysis or catheter-directed thrombolysis) and mechanical (surgical embolectomy or catheter-based thrombectomy) reperfusion strategies with regards to in-hospital mortality and major bleeding.

Results:
Among 122,735 hospitalizations for high-risk PE ECMO was used in 2,805 (2.3%); stand-alone in 1.4%, with thrombolysis-based reperfusion in 0.4%, and with mechanical reperfusion in 0.5%. Compared to neither reperfusion nor ECMO, ECMO plus thrombolysis-based reperfusion was associated with reduced in-hospital mortality (adjusted OR, 0.60; 95% CI, 0.38-0.97), whereas no difference was found with ECMO plus mechanical reperfusion (1.02; 0.66-1.59), and ECMO stand-alone was associated with increased in-hospital mortality (1.59; 1.21-2.09). In the cardiac arrest subgroup, ECMO was associated with reduced in-hospital mortality (0.71; 0.53-0.93). Among all patients on ECMO, thrombolysis-based reperfusion was significantly associated (0.54; 0.32-0.90), and mechanical reperfusion showed a trend (0.74; 0.47-1.18) towards reduced in-hospital mortality compared to no reperfusion, without increases in major bleeding.

Conclusions:
In patients with high-risk PE and refractory hemodynamic instability, ECMO may be a valuable supportive treatment in conjunction with reperfusion treatment but not as stand-alone treatment especially for patients suffering from cardiac arrest.
Abstract 15475: Comparable Program Delivery Time: Home-Based versus Hospital-Based Cardiac Rehabilitation
Authors: Fletcher Dana R , Martinez Monica , durfee josh , hajoglou amanda , Rice Marina , Orendain Juan C , Gupta Prerna , Gritz R. Mark , Peterson Pamela
Published: December 2023

Introduction:
Home-based cardiac rehabilitation (CR) adds flexibility for patients for whom hospital-based CR may not be accessible. The ERA-NUDGE study is a pragmatic randomized study, conducted at an urban safety-net hospital, which evaluated adherence and clinical outcomes of home- versus hospital-based CR, with mobile phone messaging. The resource requirements associated with home-based CR interactions are not yet well established. We aimed to compare program delivery time between home-based and hospital-based CR programming.

Methods:
For one random week in each of 22 months, program delivery times were recorded by a research team member who shadowed hospital CR sessions and reviewed chart notes for home-based CR interactions. Among the sub-set of participants who had interactions during these weeks, we compared time spent on four types of interactions and seven educational topics.

Results:
Among 326 patients that completed the parent study, 157 patients had 415 visits during the microcosting weeks (mean of 3.8 visits per patient). Demographics shown in Table 1. Home-based patients accounted for 134 encounters (32%) during microcosting collection weeks. Six- and twelve-week follow-up visits were split between hospital- and home-based groups (53% and 47%, respectively) (Table 2).

Conclusions:
Despite documented benefits for patients from CR, access remains low. Home-based CR may present an appealing alternative for patients with difficulties around CR access, but CR program directors may be wary of added staffing requirements to deliver these alternatives. Our analysis suggests that home-based CR can be delivered to patients without increases in personnel time.
Abstract 15477: Mitochondrial Drp1 Deficiency in Macrophage Limits Revascularization of Ischemic Muscle via Inflammatory Metabolic Reprograming and Macrophage Polarization
Authors: Yadav Shikha , Ganta Vijay C , Ash Dipankar , Varadarajan Sudhahar , Nagarkoti Sheela , Das Archita , McMenamin Maggie , Fukai Tohru , Ushio-Fukai Masuko
Published: December 2023

Background:
In preclinical peripheral artery disease (PAD) models, M2-like anti-inflammatory macrophage polarization, arteriogenesis and angiogenesis are crucial in restoring perfusion recovery and revascularization. Mitochondrial dynamics in macrophage regulates cell metabolism and inflammation. Mitochondrial fission protein, Drp1 GTPase is shown to be involved in pro- or anti-inflammatory macrophage phenotypes in a context-dependent manner. However, role of macrophage Drp1 in reparative neovascularization in experimental PAD model remains unknown.

Method and Results:
Macrophage-specific Drp1 knockout (MФ-Drp1-KO; LysCre x Drp1 fl/fl) or wild type (WT) mice were used for hindlimb ischemia (HLI), a preclinical PAD model. Drp1 expression was dramatically increased in F4/80
+
macrophage in ischemic muscle at day 3 after HLI of WT mice. MФ-Drp1-KO mice showed decreased limb perfusion (78.3%), angiogenesis (53.0 %), arteriogenesis (46.3%), and muscle regeneration (41.9%) after HLI. This was associated with increased pro-inflammatory M1-like MФ (2.2 fold by FACS analysis), p-NFkB and TNFα expression and decreased anti-inflammatory M2-like MФ (2.3 fold by FACS analysis) and p-AMPK in ischemic muscle of MФ-Drp1-KO mice vs. WT mice. In vitro, bone marrow-derived MФ with hypoxia serum starvation (HSS) (in vitro PAD model) induced mitochondrial fission and activated Drp1.

Drp1
KO

MФ under HSS exhibited increased glycolysis (66.7%, ECAR) via reduced p-AMPK as well as excess mitochondrial (mito)ROS production (2 fold), which in turn increased M1-genes (
Nos2
and
Ptgs2
) and decreased M2-genes (
Arg1
and
Retnla
). These responses in

Drp1
KO

MФ were rescued by AMPK activator AICAR and mitoROS scavenger mitoTEMPO. Finally, conditioned media from HSS-treated

Drp1
KO

MФ showed increased secretion of pro-inflammatory TNFα and GAPDH and suppressed angiogenic responses of cultured endothelial cells (50%).

Conclusion:
Drp1 dysfunction in macrophage promotes inflammatory macrophage polarization induced by hyperglycolysis via suppression of anti-inflammatory AMPK as well as excess mitoROS, which limits revascularization in experimental PAD.
Abstract 15500: Identifying Cardiomyocytes at Specific Cell-Cycle Stages by a New Cell-Cycle-Specific snRNAseq Analytic Method
Authors: Nguyen Thanh , Nakada Yuji , Zhang Jianyi J
Published: December 2023

Background:
Deciphering the cardiomyocyte cell cycle is a critical question in studying heart development and regeneration. We already collected the single-nuclei RNA sequencing (snRNAseq) data from fetal pig hearts and from pigs that underwent apical resection on postnatal day (P) 1 (AR
P1
) followed by myocardial infarction (MI) on P28 (MI
P28
); in these hearts, robust cardiomyocyte proliferation was confirmed.

Research questions:
Although our previous snRNAseq analyses found cardiomyocyte clusters that primed to proliferate, each of these clusters only appeared at one specific time point; furthermore, these clusters still contain a significant amount of non-cycling cell; and thus, we were unable to distinguish between cardiomyocytes in different phases of the cell cycle.

Approach:
In this report, we designed a new Autoencoder that only utilized 1646 cell-cycle-specific genes to cluster cardiomyocytes and applied the Autoencoder on pig heart GEO datasets number GSE185289.

Results:
Five cardiomyocyte clusters (pCM1+2, pCM3-pCM6) were identified. Five proliferation markers (AURKB, MKI67, INCENP, CDCA8, and BRCA5) highly co-expressed in pCM1+2; also, the top enriched gene ontologies of pCM1+2 were all related to cell-cycle. PCM1+2 percentages were ~6% in fetal hearts and ~2-3% in hearts from ARP1MIP28 pigs during the two weeks after MI induction but were nearly undetectable in all other experimental groups and at all other time points. We also identified four transcription factors (E2F8, FOXM1, GLI3, and RAD51) that explicitly coexpressed within pCM1. Also, a pseudo-time trajectory was constructed in Fetal cardiomyocyte, which began at pCM3 (G1/S phase, CCND2 localization), passed through pCM2 (S phase, CCNE2 localization), and ended at pCM1 (M phase, CCNB2 localization).

Conclusions:
Applying the more precise cell-cycle specific Autoencoder, we found three clusters that likely represented cardiomyocytes at three different cell-cycle stages.
Abstract 15514: Ambulating Femoral Inserted Intra-Aortic Balloon Pump: Is It Safe?
Authors: Chonde Meshe , seidel suzanne , Villao Billy , Aronow Harriet , Hsu Sunny , Coleman Bernice L , Velazquez Miguel , Andreas Anthony , Chan Alice T
Published: December 2023

Introduction:
Patients undergoing heart transplant evaluation wait in the hospital for weeks. The intra-aortic balloon pump (IABP) is commonly used as a bridge to heart transplants. However, patients with a femoral-inserted IABP may face mobility limitations. Goal: To address this issue, the Cardiac Intensive Care Unit (CICU) implemented a modified Ramsey protocol aimed at ambulating patients with IABP.
Goals:
The goal was to improve patient health outcomes. The project aims to ambulate patients with f-IABP in Cardiac Intensive Care Unit (CICU) to prevent functional decline due to bed rest.

Methods:
The provider prescribed all IABP patients in the CICU ambulation. Before ambulation, patients who met the criteria were verticalized, utilizing the KREG Catalyst™ bed at 70 degrees for at least 45 minutes three times/day. After tolerating the verticalization at 70 degrees, nurses and physical therapists will assist the patient in stepping off the bed for at least 45 minutes 2 before ambulating around the unit.

Results:
A total of 14 patients were ambulated, of which twelve were male and two were female. The mean aged is 59 years, ranging from 30 to 72 years. The participants underwent an average of 15 ambulation sessions, with the minimum being one session and the maximum being 52 sessions. During these sessions, the participants covered an average total distance of 9619.29 feet, ranging from a minimum of 70 feet to a maximum of 36250 feet. The participants spent an average of 4061.86 seconds ambulating, with a minimum duration of one minute and a maximum of 30 minutes. The average catheter migration was 0.2229 centimeters upon implementation of the intervention. The findings show no significant adverse events with implementing this protocol.

Conclusions:
By implementing this protocol, healthcare professionals can enhance patient care and optimize post-heart transplant length of stay.
Abstract 15515: SGLT2 Inhibitor Empagliflozin Increases Fatty Acid Oxidation, Coupling Between Glycolysis and Glucose Oxidation, and Decreases Left Ventricular Hypertrophy in Mice With Hypertrophic Cardiomyopathy Due to Myosin R403Q Mutation
Authors: Baka Tomas , Moore Jarrod , Qin Fuzhong , He Huamei , Chambers Jordan M , Croteau Dominique , Goel Raghuveera , Zhang Aifeng , Smith Hunter , Balschi James A , Pimentel David R , Seidman Christine E , Seidman Jonathan G , Emili Andrew , Colucci Wilson S , Luptak Ivan
Published: December 2023

Background:
A metabolic switch from fatty acid oxidation (FAO) to glycolysis associates with LV hypertrophy (LVH). Glucagon signaling increases FAO in the heart and sodium-glucose co-transporter 2 inhibitors (SGLT2i) raise glucagon/insulin ratio (GIR) in patients. We have shown that SGLT2i reprogram cardiac metabolic genes favoring FAO, yet the mechanism is unknown.

Hypothesis:
SGLT2i increases GIR, thereby increasing FAO and glycolysis/glucose oxidation coupling (GGC), which in turn attenuates LVH and fibrosis in a murine model of HCM (R403Q myosin mutation).

Methods:
Mice 9 weeks of age were treated ± SGLT2i empagliflozin (EMPA, 0.15 mg/g chow). After 2 weeks, prior to LVH onset, myocardial transcriptomic analysis was performed. After 16 weeks, echocardiography, proteomics, fasted GIR, and histology were obtained. Glucose fluxes, energetics and
13
C substrate oxidation were measured in isolated beating hearts by
31
P and
13
C NMR spectroscopy.

Results:
R403Q mice had ↓GIR which was normalized by EMPA. Transcriptomics (2 weeks) and proteomics (16 weeks) confirmed downregulation of electron transport and FAO pathways, and upregulation of LVH and fibrosis pathways. At 16 weeks, R403Q hearts exhibited LVH, fibrosis, ↓diastolic function and ↓contractile reserve (rate pressure product increase between low and high workload). Metabolically, R403Q had ↑glucose uptake and ↓GGC with ↑lactate production; ↓FAO and impaired energetics (↓free energy of ATP hydrolysis, ΔG
~ATP
, at both workloads). The HCM phenotype and all measures of metabolic dysfunction were partially or completely prevented by EMPA.

Conclusion:
R403Q hearts display marked metabolic reprogramming that appears early in the disease process and leads to energetic dysfunction. SGLT2i corrects GIR, attenuates metabolic reprogramming and the energetic, structural and functional features of HCM. SGLT2i and possibly other measures to modulate glucagon signaling hold therapeutic potential in HCM.
Abstract 15519: Frailty is Associated With Incident Heart Failure in US Veterans Across Multiple Frailty Indices: The Million Veteran Program
Authors: Qazi Saadia , Seligman Benjamin , Preis Sarah R , Rane Manas , Wilson Peter W , Djousse Luc , Gagnon David , Gaziano Michael , Driver Jane , Cho Kelly , Orkaby Ariela
Published: December 2023

Introduction:
Frailty, a syndrome of physiologic vulnerability, increases cardiovascular disease (CVD) risk via overlapping mechanisms such as inflammation, insulin resistance, and cellular senescence. However, the association of frailty with incident heart failure (HF) has not been well characterized. We calculated three distinct frailty scores and examined their association with HF in the Million Veteran Program (MVP).

Methods:
Participants comprised U.S. Veterans aged 50 years or older at baseline (2011-2018) enrolled in the prospective MVP study who were free of HF. We calculated frailty using three validated approaches: primarily the 36-item MVP-frailty index (FI) based on questionnaire data, 31-item Veterans Administration-FI (VA-FI) EHR-based index, and the 3-item Study of Osteoporotic Fractures (SOF) physical frailty score. Incident HF was ascertained via ICD-9 and ICD-10 codes. Multivariable-adjusted Cox proportional hazards models were constructed to assess the association between frailty status via each index and incident HF.

Results:
Among 190,688 Veterans (aged 69 ±9 years, 94% male), using the MVP-FI frailty screening tool, 29% were robust, 42% were pre-frail, and 29% were frail. Frailty prevalence increased by age, from 27% among 50-59-year-olds to 42% among those 90 years or older. Over a mean follow-up of 6±2 years, 15,816 (8.3%) Veterans developed incident HF. Pre-frail and frail compared to robust Veterans had nearly a 1.5-fold and 3-fold hazard of HF, respectively. The VA-FI and SOF indices yielded concordant findings (Table).

Conclusion
Among US Veterans aged 50 years or older, frailty was associated with incident HF. A graded increase in the hazard of HF occurred with increasing level of frailty, irrespective of frailty tool used. The present analysis lays the groundwork for future studies needed to further define the role of frailty in the pathogenesis of HF and inform clinical interventions for prevention of frailty and downstream HF.
Abstract 15530: Intravenous Thrombolysis in Patients With Ischemic Stroke on Direct Oral Anticoagulants: A Systematic Review and Meta-Analysis
Authors: Gupta Rahul , Behnoush Amir Hossein , Khalaji Amirmohammad , Bahiraie Pegah , Malik Aaqib H , Bandyopadhyay Dhrubajyoti , Goel Akshay , Aronow Wilbert S , PATEL NAINESH , kluck bryan
Published: December 2023

Introduction:
Current guidelines recommend avoiding intravenous thrombolysis (IVT) in patients with ischemic stroke who are on direct oral anticoagulants (DOAC). However, studies found conflicting results regarding IVT safety and functional outcomes among patients receiving DOACs.

Hypothesis:
Herein, we aim to investigate this association through a systematic review and meta-analysis.

Methods:
A comprehensive literature search was performed in PubMed, Embase, Scopus, and the Web of Science. Studies were included if they compared the outcomes of patients receiving DOACs and those without recent use of DOACs. Random-effect meta-analysis was performed to calculate the odds ratio (OR) and 95% confidence interval (CI) for comparison of modified Rankin Score (mRS) 0-2, all-cause mortality, and symptomatic intracranial hemorrhage (sICH).

Results:
A total of five studies were included among which 3,408 received DOACs and 244,033 did not. Random-effect meta-analysis revealed that the functional neurological outcome (mRS 0-2) was significantly lower in patients that received DOACs (OR 0.71, 95% CI 0.62-0.81, p<0.01). However, this difference was no longer significant in the subgroup analysis of 90 days mRS 0-2 (OR 0.71, 95% 0.46-1.11, p=0.14). Regarding all-cause mortality, patients on DOAC had a higher overall mortality rate (1.26, 95% CI 1.07-1.48, p=0.01). Nevertheless, this was not true for subgroups of in-hospital and 90-days mortality, which were both insignificant. Finally, sICH did not differ between the groups (OR 0.99, 95% CI 0.70-1.39, p=0.93).

Conclusions:
Our results demonstrated that the use of IVT in selected patients on DOACs with stroke might be beneficial and not associated with increased risk as there was no difference between the groups in terms of sICH.
Abstract 15562: Coronary Artery Calcium Score for Allocating Emerging Obesity Therapies: Implications for the Ongoing SURMOUNT-MMO Outcome Trial
Authors: Tasdighi Erfan , Grandhi Gowtham , Boakye Ellen , Blaha Michael J
Published: December 2023

Background:
Tirzepatide demonstrated substantial weight loss in patients with obesity yet without diabetes and the clinical trial (SURMOUNT-MMO) evaluating its CVD benefits is ongoing. We tested whether the CAC score provides substantial risk predictive value in this setting.

Methods:
Participants (N=16,163; mean age 53.0 ± 9.7 years; 72.5% men) with BMI≥ 27 kg/m
2
but without diabetes from the CAC Consortium were categorized based on the inclusion criteria of SURMMOUNT-MMO trial pertaining to individuals without an established CVD. The predictive value of CAC was evaluated for all-cause and cause-specific mortality after mean follow-up of 10.6 ± 2.9 years using multivariable-adjusted Cox proportional hazard and competing risks regression, respectively.

Results:
Of the 16,163 participants, 14,004 (86.6%) would not qualify for the SURMMOUNT-MMO trial. Of those, those with CAC ≥ 300 had a higher rate (per 1,000 person-years) of all-cause (7.10 vs. 1.43), CVD (2.62 vs. 1.0), and CHD (1.61 vs. 0.75) mortality compared to ones with CAC=0. After adjusting for age, sex, and race, individuals who would not qualify and with CAC≥ 300, had significantly higher risk of all-cause, CVD, and CHD mortality (all P-values <0.001), compared to those who do not qualify and without CAC. Of note, individuals who would qualify but with CAC <100 did not have increased all-cause, and cause-specific mortality compared to individual who would not qualify and without CAC (Table).

Conclusions:
CAC strongly predicts all-cause, CVD, and CHD mortality among individuals with obesity but without diabetes, and may better risk stratify than SURMOUNT-MMO inclusion criteria. CAC may serve as an effective risk stratification tool to prioritize the allocation of therapies for weight management.