bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 14638: NPA7: A Novel Designed Bispecific Peptide That Protects Human Cardiomyocytes Against Oxidative Stress Through the GC-A/Mas Receptor-KEAP1-NRF2 Pathway
Authors: ma xiaoyu , Malsawmzuali JC , Moroni Dante , Ma Xiao , Sangaralingham Jeson , Burnett John C
Published: December 2023

Introduction:
Excess cardiomyocyte oxidative stress is a major metabolic abnormality in HTN and its progression to HF. Thus, therapies that reduce oxidative stress in the heart may lead to a reduction in CVD related adverse outcomes such as HF and death. Recently, we bioengineered a bispecific peptide NPA7 that co-activates the protective GC-A/cGMP and MasR/cAMP pathways. Previously we showed that NPA7 possesses cardiorenal protective properties. However, the antioxidant effects of NPA7 within the heart is unknown.

Hypothesis:
NPA7 protects human cardiomyocytes against oxidative stress through the GC-A/Mas Receptor-KEAP1-NRF2 pathway.

Methods:
HCMs were pretreated with PBS or NPA7 (10 uM) followed by 400 uM hydrogen peroxide (H2O2) to induce oxidative stress. Intracellular ROS was measured by dihydroethidium (DHE) staining and protein levels of KEAP1 and NRF2 via western blot. The ratio of GSH/GSSG were determined by using commercial kit. mRNA levels of G6PD, GCLC, GCLM and GSS in HCMs, which represents antioxidant capacity, were determined by real-time PCR. For knockdown experiments, HCMs were transfected with the siRNA target GC-A and MasR for 24 h and then treated with NPA7 and H2O2 for another 20 h.

Results:
H2O2 increased DHE staining level, which indicated elevated intracellular ROS levels within HCMs. Notably, treatment with NPA7 decreased DHE level and increased the ratio of GSH/GSSG in HCMs with H2O2. Furthermore, NPA7 significantly increased the mRNA level of NRF2 target genes (G6PD, GCLC, GCLM, GSS) through NRF2 activation and KEAP1 degradation, indicating that NPA7 activates KEAP1-NRF2 pathway, the upstream pathway that regulate antioxidant gene expression, in HCMs. Moreover, these effects were eliminated if GC-A and MasR were silenced by siRNA, thus supporting the protective antioxidant role of both GC-A and MasR.

Conclusions:
The present study establishes an antioxidant action of NPA7, a novel bispecific designer peptide, on H2O2-induced oxidative stress by the dual targeting of GC-A and MasR through the KEAP1-NRF2 signaling pathway in HCMs. These results advance NPA7 as an innovative therapeutic strategy targeting oxidative stress related to CVD.
Abstract 14647: EchoNext: An ECG-Based Deep Learning Model to Detect Structural Heart Disease
Authors: Jing Linyuan , Finer Joshua , Hartzel Dustin , Kelsey Christopher , Rocha Daniel , Ruhl Jeffrey , Volodarskiy Alexander , Beecy Ashley , Haggerty Christopher M , Poterucha Timothy J , Elias Pierre
Published: December 2023

Introduction:
Early detection of structural heart diseases (SHD) can help improve patient outcomes. Electrocardiogram (ECG) based deep learning (DL) models have the potential to identify patients (pts) with undiagnosed disease in need of further testing such as echocardiography. Most models have focused on detecting a single abnormality. A few studies have attempted detection on a comprehensive aggregate set of outcomes, but with limited scope and external validation.

Hypothesis:
An ECG DL model can identify pts at risk for SHDs, with stable external validation performance regardless of hospital type (academic/community), clinical setting (inpatient/outpatient/emergency department), or demographics (race/ethnicity).

Methods:
We identified 426,659 ECG-echo study pairs since 2008 from 5 NewYork-Presbyterian-affiliated (NYP) hospitals, including Columbia, to train the EchoNext DL model. ECGs were associated with SHD if acquired within one year prior to an echo reporting left ventricular (LV) ejection fraction ≤45%, LV wall thickness ≥1.3cm, moderate or severe valvular disease, moderate or large pericardial effusion, moderate or severe right ventricular dysfunction, or pulmonary artery systolic pressure ≥45 mmHg. EchoNext was tested on unseen data from four other NYP hospitals, including Cornell.

Results:
In the external dataset (n=21,421 pts), 33% were identified with SHD. EchoNext achieved an area under the receiver operating characteristic curve (AUROC) of 0.85, with robust results with respect to individual hospital (AUROC range: 0.82-0.87), clinical setting (0.78-0.84), and patient race/ethnicity (0.84-0.86; Figure).

Conclusion:
EchoNext demonstrated excellent performance in detecting SHD in the largest multi-institutional, multi-racial external validation of such a model to date. This model may allow AI-enabled reflex referral to echocardiography from ECG. Prospective trials are ongoing to validate.
Abstract 14651: Noncoding RNA Drug, TY1, Attenuates Cardiac Fibrosis in Two Mouse Models of Systemic Sclerosis
Authors: Jones Xaviar M , Ciullo Alessandra , Mesquita Thassio , Fournier Mario , Liu Weixin , Li Liang , Ibrahim Ahmed G , Marban Eduardo
Published: December 2023

Introduction:
Systemic sclerosis (SSc) is a connective tissue disease characterized by inflammation and fibrosis of the skin and vital organs. The disease has no specific treatment options and a high mortality (~30% at 3 years). We have previously demonstrated anti-fibrotic and anti-inflammatory properties of EV-YF1, a small Y RNA abundant in extracellular vesicles secreted by cardiosphere-derived cells (CDCs). Here we describe the therapeutic bioactivity of a shorter, engineered derivative, TY1.

Methods:
5-7-week-old female C57BL/6J wild type mice (n=100 total) were injected with phosphate-buffered saline (PBS; WT) or 100 μL bleomycin (1 mg/ml) subcutaneously every other day for 3 weeks. Animals then received either vehicle (formulation only, in PBS), TY1, or scrambled TY1 (as an RNA control) via oral gavage. Endpoints include exercise capacity, lung weight, systolic and diastolic function by echocardiography, and histologic quantification of fibrosis in heart and skin. To confirm the antifibrotic findings in an inflammation-independent model, 4-6-week-old Tight-skin (tsk-1) mice (n=18 total) received oral TY1, scramble or vehicle for 4 weeks.

Results:
Diastolic dysfunction was evident in bleomycin mice, but was normalized by TY1 ingestion (E/E’ ratios in WT: 18.91, vehicle: 32.29, scramble: 36.19, TY1: 20.65 p <0.0001). Likewise, lung congestion and exercise intolerance were ameliorated by TY1 ingestion (p<0.0001). In both models (bleomycin-induced and tsk-1), skin and cardiac fibrosis were greater in vehicle or scramble groups than in WT, but were normalized by TY1 after 4 weeks (p <0.001).

Conclusions:
These results demonstrate the therapeutic bioactivity of a bioinspired new chemical entity in two complementary mouse models of SSc. Thus, TY1 merits investigation as a potential novel therapeutic for SSc.
Abstract 14674: Under- or Over-Estimation of Patients’ Health Status by Physicians in the Care of Patients With Atrial Fibrillation
Authors: Ikemura Nobuhiro , Kohsaka Shun , Kimura Takehiro , Katsumata Yoshinori , Tanimoto Kojiro , Ueda Ikuko , Miyama Hiroshi , Nishiyama Takahiko , Spertus John , Takatsuki Seiji
Published: December 2023

Introduction:
A primary objective of managing atrial fibrillation (AF) is to optimize patients’ health status (HS), symptoms, function, and quality of life, with an accurate assessment. However, the accuracy of physicians’ estimation of patients’ HS, and its impact on treatment decisions, remains unreported.

Aims:
To explore the discordance between physicians’ estimation and patients’ HS in those with newly-recognized AF and its association with subsequent care.

Methods:
From 2018-2020, newly diagnosed or referred AF patients at two outpatient practices in Tokyo completed the Atrial Fibrillation Effect on QualiTy of Life questionnaire (AFEQT, 20 items with a 7-point Likert scale). Blinded to patients’ AFEQT, treating physicians quantified patients’ HS using 3 items reflecting each AFEQT domain. Both physicians’ and patients’ raw responses were averaged, with higher scores indicating worse HS. We defined under-estimation as the physician reporting a score ≤-1 lower and over-estimation as a score ≥1 higher than the patient’s average. We examined the association of HS estimation with treatment and compared 1-year changes in AFEQT.

Results:
Among 330 patients with newly-recognized AF, physicians correctly estimated patients’ HS in 187 (56.7%), under-estimated its severity in 22 (6.7%), and over-estimated it in 121 (36.7%). Treatment escalation, defined as alteration or initiation of antiarrhythmic drugs, referral for cardioversion, or catheter ablation, occurred in 65.2%, 40.9%, and 61.9% of patients in the correctly, under-, and over-estimated groups, respectively. After adjusting for patient’s characteristics, under-estimation was independently associated with a lack of treatment escalation (adjusted OR 0.30, 95% CI 0.11-0.81) and with less improvement in the AFEQT Symptom scale at 1-year (-3.5 [SE 0.8] vs. 7.0 [SE 3.6] points in under- vs. correctly and over-estimated patients, P=.005)

Conclusions:
Under-recognition of AF patients’ HS is associated with less aggressive treatment and less health status improvement at 1 year. Standardized assessments of patients’ health status with validated questionnaires may help reduce under-and over-estimating patients’ HS, resulting in greater treatment appropriateness and better outcomes.
Abstract 14694: An Uncommon Mass, in an Uncommon Location, in a Common Patient?
Authors: Osuji Ngozi , Caglayan Cihan , Levene Jacqueline , Tariq Ezza F , Franz Joseph , Farah Rafic , Serna-Gallegos Derek , Fowler Jeffrey A , Toma Catalin , Olson Adam , Hansra Barinder , Levenson Joshua E
Published: December 2023

Background:
Myeloid sarcomas (MS) are rare extramedullary tumors composed of mature or immature myeloid cells. The heart is an uncommon site for this neoplasm.

Case Presentation:
A 68-year-old woman with a remote history of acute myeloid leukemia (AML) and allogeneic stem cell transplant presented with dyspnea. Her oxygen saturation was 70% on room air. Transthoracic echocardiography (TTE) revealed a nonhomogeneous intrapericardial mass measuring 6.3 cm by 10.0 cm, invading the right atrium and compressing the right ventricle (Figure 1). Due to persistent hypoxia, additional investigation with agitated saline contrast revealed a right-to-left intra-cardiac shunt. Cardiac magnetic resonance imaging showed invasion of the right and left ventricles, extension into the superior vena cava, and encasement of the right coronary artery. Due to worsening hypoxemia, vasopressin infusion and inhaled epoprostenol were initiated to reduce intracardiac shunting. Direct cardiac mass biopsy was considered prohibitive risk, however, a pericardiocentesis allowed for cytologic analysis of pericardial fluid which revealed atypical white blood cells, and subsequent flow cytometry indicated an aberrant myeloid population with monocytic features consistent with MS. She initiated chemotherapy with decitabine and low dose cytarabine. On day 6 of chemotherapy, she started external beam radiation therapy. A repeat TTE on day 10 of therapy showed a marked reduction in tumor size and intracardiac shunting.

Discussion:
MS can manifest before the development of bone marrow disease, following treatment for bone marrow disease, as relapse or progression of previous myelodysplastic or myeloproliferative neoplasms. With approximately fifty cases reported in the literature, most achieved temporary remission. Our approach to management included chemotherapy with decitabine and cytarabine and subsequent external-beam radiotherapy.
Abstract 14698: Effect of Torsemide vs. Furosemide Among Patients With New Onset and Worsening Heart Failure: The Transform-HF Randomized Trial
Authors: KRIM SELIM R , Anand Senthil , Greene Stephen J , CHEN ANQI , Wojdyla Daniel , Vilaro Juan , Herbert Haught , Herre John M , Eisenstein Eric L , Anstrom Kevin , Pitt Bertram , Velazquez Eric J , Mentz Robert J
Published: December 2023

Introduction:
In the TRANSFORM HF trial, among patients discharged after hospitalization for heart failure (HF), torsemide compared with furosemide did not result in a significant difference in all-cause mortality over 12 months.

Hypothesis:
Differences in clinical profiles, outcomes, and treatment effects may exist between de-novo and worsening chronic HF (WHF) patients.

Methods:
Using data from TRANSFORM-HF trial, we compared clinical characteristics, outcomes, and treatment effect of torsemide versus furosemide of patients hospitalized with de novo versus WHF. Endpoints included all-cause mortality and hospitalization outcomes over 12 months, as well as change from baseline in KCCQ-CSS.

Results:
Among 2,858 patients, 838 (29.3%) patients had de novo HF and 2,020 (70.7%) patients had WHF. Irrespective of ejection fraction phenotype, de novo HF patients were younger, had a higher GFR and lower levels of natriuretic peptides. In contrast, a higher discharge diuretic dose along with a higher use of nitrate/hydralazine was noted among WHF patients. De novo HF was associated with lower all-cause mortality (de novo 13.7% vs. WHF 31.3%; adjusted hazard ratio: 0.53; 95%CI [0.43-0.66]; p<0.001). Similarly, lower all-cause first re-hospitalization (de novo 30.3% vs. WHF 42.5%; adjusted hazard ratio: 0.72; 95%CI [0.64-0.81]; p<0.001) and greater improvement in KCCQ-CSS at 12 months (de novo 29.9 vs. WHF 23.7; adjusted estimated difference in means: 6.3; 95%CI [3.7-8.8]; p<0.001) were noted among de novo HF patients. No significant differences in mortality or hospitalizations were noted with torsemide versus furosemide in either de novo or WHF (Figure).

Conclusions:
Among patients discharged with acute HF, de novo HF was associated with better outcomes when compared to WHF. Regardless of de novo vs WHF status, there was no significant difference between torsemide and furosemide with respect to 12-month clinical or patient-reported outcomes.
Abstract 14701: Agreement Between Handheld and Standard Echocardiography for Diagnosis of Latent Rheumatic Heart Disease in Brazilian Schoolchildren From High-Prevalence Settings
Authors: Nascimento Bruno R , Oliveira Kaciane , Veloso Jessica Elvira M , Silva Cássia Aparecida , Nunes Maria D , Abrams Jessica , Diniz Marina G , Diamante Lucas , Amaral Arthur M , Santos Luiza P , Franco Juliane , Galdino Bruno F , Barbosa Marcia M , TACURI CHAVEZ LUZ MARINA , Fraga Lucas , Meira Zilda Maria A , Ribeiro Antonio L , Sable Craig A
Published: December 2023

Background:
Handheld echocardiography (echo) is the tool of choice for Rheumatic Heart Disease (RHD) screening, based on the 2012 World Heart Federation (WHF) Criteria. We aimed to assess the agreement between screening and standard echo for diagnosis of latent RHD in schoolchildren from an endemic setting.

Methods:
Over 14 months, 3 non-physicians used handheld machines (GE, VSCAN) and the 2012 WHF Criteria to determine RHD prevalence in low-income public schools in Minas Gerais, Southeast Brazil. Consented children were eligible for participation. Studies were interpreted remotely using a telemedicine cloud-server by 2 experts in Brazil and the US. RHD-positive children (borderline and definite) and those with congenital heart disease (CHD) were referred for standard echo with portable devices (GE, Vivid IQ), with acquisition and interpretation by an expert cardiologist. Agreement between screening and standard echo, by category and according to the WHD criteria, was assessed, and the kappa statistic was applied.

Results:
A total of 1,390 students were screened in 6 schools and, among these, 110 (7.9%, 95% CI 6.5 - 9.5) were screen-positive and referred for standard echo, with mean age of 14±2 years, 80 (72%) women. Among the 16 cases initially diagnosed as definite RHD, 11 (69%) were confirmed, 4 (25%) reclassified to borderline and 1 to normal. Among the 79 cases flagged as borderline RHD, 19 (24%) were confirmed, 50 (63%) reclassified to normal, 8 (10%) to definite RHD and 2 had mild CHD. Among 11 children with CHD in screening, 4 were confirmed, 5 were reclassified to normal and 2 to RHD. Considering the 4 diagnostic categories, kappa was 0.18. In patients with borderline RHD reclassified to non-RHD, the most frequent WHF criteria was B (isolated mitral regurgitation): 64%, followed by A (2 morphological features of the mitral valve): 31%. In the only patient with definite RHD reclassified to normal, WHF criteria was D (borderline RHD in aortic and mitral valves). After standard echo, RHD prevalence was 3.2% (95% CI 2.3 - 4.2).

Conclusions:
Although practical, RHD screening with handheld devices tend to overestimate prevalence. Even in endemic settings, continuous education for detection, and application of risk stratification for management are crucial.
Abstract 14703: Platelet Reactivity and Long-Term Outcomes Following Acute Myocardial Infarction
Authors: Larsen Peter D , Holley Ana S , Hally Kathryn E , Harding Scott A
Published: December 2023

Introduction:
A large volume of literature demonstrates a short term (1 year) association between high on treatment platelet reactivity in patients with acute myocardial infarction treated with clopidogrel and adverse cardiovascular outcomes. There is less literature examining whether this association extends beyond the duration of clopidogrel treatment.

Hypothesis:
That on-treatment platelet reactivity is associated wtih 5-year death and recurrent myocardial infarction in patients with acute myocardial infarction.

Methods:
We measured platelet reactivity in patients presenting with AMI to Wellington Hospital between 2012 and 2015 who had been treated with clopidogrel prior to angiography using Multiplate P2Y
12
assay (Roche Diagnostics). Platelet reactivity was measured in platelet reactive units (PRU). We examined the relationship between PRU and both death and myocardial infarction at 5 years follow-up.

Results:
In 921 patients with acute myocardial infarction (mean age 63.2, sd 10.8, 81% NSTEMI 19% STEMI) mean PRU was 39.3 (sd 23.6) PRU, with 74 patients (8%) having a PRU greater than 47, previously described as high on treatment platelet reactivity. 5-year mortality was observed in 10.4% (96 cases) and recurrent myocardial infarction in 12.2% (122 cases). Platelet reactivity was significantly associated with 5-year mortality in Receiver Operator Curve analysis, with AUC 0.58, p=0.009. Mean PRU was 45.8 (sd 27.5) in those who died versus 38.4 (sd 23.2) in those still alive at 5 years (p=0.004, unpaired t-test). Cox regression analysis demonstrated a hazard ratio of 1.01 (95% CI 1.003-1.017, p=0.01) for each increasing unit of PRU. Recurrent MI was not significantly associated with PRU, with an AUC of 0.55, p=0.09).

Conclusions:
Levels of platelet reactivity were associated with long-term mortality risk in AMI patients. This may suggest platelet reactivity in the acute phase following an AMI is a marker of poor cardiovascular repair, leading to an association with long-term mortality risk
Abstract 14705: Diastolic Function is Uniquely Augmented by Direct Mechanical Ventricular Actuation in the Failing Heart
Authors: Schmitt Benjamin A , Zhou Yirong , Anstadt Mark P
Published: December 2023

Introduction:
Diastolic dysfunction represents a significant pathophysiology in cardiomyopathies and heart failure (HF), yet limited therapies exist for treatment. Direct Mechanical Ventricular Actuation (DMVA) is a non-blood contacting device highly unique in its ability to provide both diastolic and systolic support. The purpose of this study was to further evaluate DMVA’s effect on diastolic function in the failing heart.

Methods:
Adult canine (63.7 ± 13.4 lb, n=9) underwent repeated cycles of ventricular fibrillation to generate progressive levels of acute HF. DMVA was applied to support HF after defibrillation. Intracardiac echocardiography was used to quantify LV longitudinal strain/strain rates using speckle-tracking algorithms. Strain/strain rate peak magnitudes and composite waveforms were analyzed during baseline (n = 35), DMVA (n = 127), and non-support HF (n = 127). One-way ANOVA with post-hoc Tukey’s HSD was used to assess statistical differences (p<0.05) for all comparisons.

Results:
LV strain metrics were augmented during DMVA support (strain: 20.0 ± 0.5 %, strain rate: systolic, -1.64 ± 0.03 1/s, diastolic, 1.68 ± 0.04 1/s) versus non-supported HF (strain: 9.9 ± 0.2 %, p<0.001, strain rate: systolic, -0.83 ± 0.02 1/s, p<0.001, diastolic, 0.86 ± 0.02 1/s, p<0.001). All strain metrics were increased during DMVA compared to baseline (strain: 14.2 ± 0.4 %, p<0.001, strain rate: systolic, -1.11 ± 0.03 1/s, p<0.001, diastolic, 1.14 ± 0.04 1/s, p<0.001). Composite strain waveforms aligned by systolic peak revealed an early diastolic boost during DMVA relative to baseline (see figure).

Conclusions:
Diastolic strain dynamics were significantly improved during DMVA in this model of progressive HF. Direct cardiac compression devices can impair diastolic function, which limits feasibility for circulatory support. This study further validates that DMVA restores near physiologic LV strain patterns during HF and uniquely augments diastolic function.
Abstract 14731: T-wave Oversensing Secondary to an Inappropriate ICD Shock Resulting in Subsequent Unnecessary Shocks
Authors: Soni Bosky , Melanie Reed , Anno Tony , Olshansky Brian , Di Biase Luigi , Patel Neil , Lakkireddy Dhanunjaya R , Gopinathannair Rakesh
Published: December 2023

Introduction:
Inappropriate ICD shocks commonly result from persistent atrial arrhythmias or oversensing. We report a scenario where an ICD shock for a rapid, sustained atrial tachycardia (AT) resulted in T-wave oversensing (TWO), triggering further inappropriate shocks.

Presentation:
A 69-year-old woman with secondary prevention dual chamber ICD underwent pulmonary vein isolation for symptomatic paroxysmal atrial fibrillation (AF). The patient remained free of AT/AF off antiarrhythmics for 3 months after the procedure when she was admitted with four consecutive ICD shocks. Electrolytes were within normal limits. Device interrogation showed that the first shock was triggered by a rapid, sustained AT (cycle length: 270 msec) detected in the VF zone (single zone device; 280 msec cut-off) and failed ATP. Following the first shock, an irregular AT ensued, with cycle length ranging from 280-370 msec, but now with high amplitude T-waves in the RV channel, resulting in TWO and three subsequent inappropriate shocks (Figure). She received IV metoprolol and digoxin with subsequent resolution of AT and TWO. Beta-blocker dosing was increased and she has remained free of AT/AF at 6 month follow-up.

Conclusions:
ICD shocks can trigger marked repolarization changes in near-field intracardiac RV electrograms resulting in TWO and subsequent appropriate shocks. Further studies are warranted to understand the mechanism underlying this phenomenon and potential risk for these events.
Abstract 14741: Value of Coronary Artery Calcium Testing in Asymptomatic Individuals With Prediabetes: A Multi-Cohort Study
Authors: Al Rifai Mahmoud S , Al-Mallah Mouaz , Blaha Michael J , Patel Jaideep , McEvoy John , Nasir Khurram , Shahid Izza , Patel Kershaw , Sharma Garima , Marrugat Jaume , Tizon Helena , Erbel Raimund , Stang Andreas , Joeckel Karl , Lehmann Nils , Schramm Sara , Schmidt Boerge , Blumenthal Roger S , Virani Salim S , NAMBI VIJAY , Cainzos Miguel
Published: December 2023

Background:
The population of adults with prediabetes is growing worldwide. The value of coronary artery calcium (CAC) testing to assess ASCVD risk in this group is poorly defined.

Methods:
We pooled participants free of clinical ASCVD from 4 prospective cohort studies including the Multi-Ethnic Study of Atherosclerosis (MESA), Heinz Nixdorf Recall (HNR) Study, Framingham Heart Study (FHS), and Jackson Heart Study (JHS). Participants were classified as having euglycemia, prediabetes, and diabetes. Cox proportional hazards models were used to study the association between glycemia status and CAC burden and incident ASCVD, adjusting for potential confounders.

Results:
The study population included 14,780 participants with mean (SD) age 58 (11) years, 54% women, 57% White, 27% Black, and 16% Other. A total of 11,429 had euglycemia, 810 had prediabetes, and 2,207 had diabetes. The distribution of CAC is shown in Panel A. Among those with prediabetes, 31% had CAC
>
100. Individuals with prediabetes and CAC
>
100 had higher event rates than participants with diabetes and those with diabetes and a guideline indication for GLP1RA/SGLT2i therapy (Panel B). In adjusted analyses, compared to individuals with euglycemia, the HR (95% CI) for ASCVD was 0.70 (0.41, 1.19) for prediabetes and CAC=0, 1.10 (0.76, 1.06) for prediabetes and CAC 1-99, 1.80 (1.37, 2.38) for prediabetes and CAC≥100, 1.82 (1.56, 2.13) among those with diabetes and 1.69 (1,42, 2.02) among those with diabetes and an indication for GLP1RA/SGLT2i.

Conclusion:
CAC
>
100 is frequent among individuals with prediabetes and identifies a subgroup at very high risk of ASCVD events. Adjusted 10-year ASCVD risk among individuals with prediabetes and CAC ≥100 is similar compared to people with diabetes and those with a guideline indication for GLP1RA/SGLT2i. Future clinical trials should assess whether individuals with prediabetes and CAC ≥100 benefit from cardiovascular risk-reduction with GLP1RA and/or SGLT2i.
Abstract 14742: Clinical Predictors of Bleeding Complications Following Percutaneous Ventricular Assist Device Insertion: Insights From the J-PVAD (Japanese Registry for Percutaneous Ventricular Assist Device) Registry
Authors: Sano Madoka , Toyota Toshiaki , Murai Ryosuke , Okada Taiji , Sasaki Yasuhiro , Taniguchi Tomohiko , Ooka Junichi , Kim Kitae , Kobori Atsushi , Ehara Natsuhiko , Kinoshita Makoto , Furukawa Yutaka ,   J-PVAD Investigators
Published: December 2023

Introduction:
Bleeding complications are significant concerns in clinical use of percutaneous ventricular assist devices (PVAD). This study aimed to identify predictors of bleedings in PVAD use.

Methods:
We analyzed 3059 cases from the J-PVAD registry, a comprehensive national registry of PVAD use in Japan, excluding 53 cases without follow-up data. Patients were stratified based on whether they had acute coronary syndrome (ACS) on the onset or not, and incidence of bleeding was evaluated within each stratum, considering the clinically selected variables, including other mechanical circulatory support (MCS) use. Risk factors were explored through multivariate analyses. The primary outcome measure was any bleeding, while major bleeding was defined as a composite of cerebral bleeding, severe bleeding (defined as life-threatening, hospitalization-requiring, disability-causing, or congenital anomaly-inducing bleeding events), and blood transfusions.

Results:
The median follow-up period was 32 days. The cohort included 1459 patients with ACS and 1575 without ACS. The incidence of any bleeding did not differ significantly between the ACS and Non-ACS stratum (30-day incidence: 25.4% and 27.6%, P = 0.57, respectively). We observed the same trends for major bleeding. Most any bleeding or major bleeding occurred on the day of insertion of PVAD or within a few days. The groups with MCS had significantly more bleeding complications than those without MCS in each stratum (Figure). In a multivariate analysis using the Cox proportional hazards model, adding MCS on PVAD was the most potent predictor of any bleeding in both strata, with the effects of other variables being modest by comparison.

Conclusions:
Bleeding complications post-PVAD insertion are often severe and occur shortly after the procedure. Although the incidence of bleeding complications did not differ significantly according to the onset type, the MCS use strongly predicted bleeding complications.
Abstract 14751: A Rare Presentation of 5-Fluorouracil-Induced Cardiotoxicity
Authors: Moshman Rachel , Rehman Muhammad Hassan , Safren Lowell , cha rido
Published: December 2023

Background:
5-fluorouracil (5-FU) is associated with numerous cardiotoxic effects, most commonly chest pain and acute coronary syndrome. Less common effects include arrhythmias, myocarditis, pericarditis, and heart failure. We present a rare case of 5-FU causing cardiogenic shock.

Case:
A 54-year-old man with metastatic esophageal adenocarcinoma presented at 3:50 with chest pain that began the day before at 16:00, shortly after starting a 5-FU pump. Electrocardiogram (EKG) showed normal sinus rhythm with no ST or T wave changes. High sensitivity troponin T was 18 ng/L, followed by 24 ng/L at 1 hour and 81 ng/L at 6 hours. Computed tomography angiography (CTA) ruled out pulmonary embolism. Transthoracic echocardiogram (TTE) showed a globally reduced left ventricular ejection fraction (LVEF) of 35-40%. The patient received metoprolol and was scheduled for coronary CTA to investigate for coronary disease. Over the next few hours, he continued to report chest pain. Repeat troponin at 18:12 was 235 ng/L. Repeat EKG showed new anterior ST depressions. Posterior EKG did not show ST elevations. Repeat TTE revealed LVEF of 15%. The patient underwent left and right heart catheterization at 21:14, which showed normal coronary arteries, pulmonary artery pressure 50/31 mmHg (mean 38 mmHg), pulmonary capillary wedge pressure 36 mmHg, and cardiac index 1.1 L/min/m
2
. An Impella device was placed for circulatory support. He was treated with vasopressors and milrinone. Given concern for 5-FU toxicity, he received the antidote uridine triacetate 10 g IV every 6 hours for 5 days. LVEF improved to 70%. He was treated with nifedipine for possible coronary vasospasm. He was discharged 8 days later with heart failure medications.

Conclusion:
The incidence of cardiotoxicity from 5-FU ranges from 1.2-18%. Mechanistic theories include coronary vasospasm and direct cellular injury. Symptoms usually present within 12 hours of initiation but may present up to 2 days later. Management includes stopping the offending agent and starting anti-anginal drugs and uridine triacetate. Uridine triacetate is deacetylated to uridine, which prevents cell damage and death via competitive inhibition of 5-FU.
Abstract 14753: Cigarette Smoking is Acutely Associated With Increased Cardiac Arrhythmias
Authors: Yang Michelle , Yilmaz Defne , Tang Janet , Chang Kathleen , Wall Grace , Marcus Gregory M
Published: December 2023

Background:
Chronic cigarette smoking is a known risk factor for the eventual development of atrial fibrillation (AF). However, the acute effects of cigarette smoking on arrhythmias in patients with AF have not been elucidated.

Methods/Approaches:
We conducted a prospective observational study enrolling consenting adults with a diagnosis of paroxysmal AF and who actively smoked. Participants were equipped with continuously recording ECG devices (iRhythm, San Francisco, CA) for up to 14 days and used a smart lighter (Quitbit, San Francisco, CA or Slighter, Cary, NC) or button presses on the ECG device to time-stamp cigarette smoking events in real-time. Outcomes included any AF, atrial flutter (AFL), supraventricular tachycardia (SVT), ventricular tachycardia (VT), atrial ectopic rhythms (EAR), and ventricular bigeminy and trigeminy. For this case-crossover study, we used a generalized linear mixed model with a Poisson distribution and accounted for the clustering of repeated measures for each participant to estimate the incidence rate ratio (IRR) between arrhythmias and smoking events.

Results:
We enrolled 29 participants (45% female, mean 55 ± 13 years old, 76% non-Hispanic white), where 22 used a smart lighter, and 7 relied on real-time button presses to document smoking events. Mean study duration was 12 ± 4 days. While wearing the monitor, 24 participants experienced ≥ 1 arrhythmia, including AF (n = 3), SVT (n = 19), VT (n= 5), EAR (n = 23), and ventricular bigeminy/trigeminy (n =12), and 9 participants had ≥ 1 sustained arrhythmia (arrhythmic events >30 secs). Every additional cigarette smoked per day was associated with a 6% increase in arrhythmia events (IRR 1.06, 95% CI 1.05-1.07, P < 0.001;
Figure
). No statistically significant relationships were observed between smoking events and sustained arrhythmias per day.

Conclusion:
The data suggest smoking acutely increases the chance an arrhythmia will occur.
Abstract 14768: Elevated Baseline Serum High Sensitivity Cardiac Troponin Levels and Mortality Post Transcatheter Aortic Valve Replacement: A Meta-Analysis
Authors: Mellacheruvu Sai Priyanka , Mohammed Adil S , Santhosh Sarayu , Makarla Venkata Akhil , Soni Roshni , Siddiqui Muneeb , Perera Ayodya , Mohammed Bilal Khan , Gandhi Zainab , Mohammed Zaki Ur Rahman , Singh Sandeep , Desai Rupak
Published: December 2023

Introduction:
High-sensitive cardiac troponins (hs-cTn) have been associated with worse prognosis and increased mortality post transcatheter aortic valve replacement (post-TAVR). However, limited data on the association prompted us to perform a meta-analysis for further understanding.

Methods:
PubMed, SCOPUS and Google Scholar were searched until May 2023 using relevant keywords. A random effects model was employed to estimate the odds of pooled pre-procedural hs-cTn levels and post-TAVR mortality. Inter-study heterogeneity was assessed using I2 statistics, and leave-one-out sensitivity analysis was performed with a significance level of p<0.05

Results:
The final analysis included six studies (n=4672) with a mean age of 82.7±5.6 and 46% female participants. There are 2 retrospective and 3 prospective studies with median follow up of 1 year. The population exhibited a high prevalence of hypertension, hyperlipidemia, and diabetes. All individuals who underwent TAVR had aortic valve area measuring <1cm2. The combined mean logistic EuroSCORE was calculated as 20.91%±12.88. An increase in pre-procedural hs-cTn levels was associated with significantly higher unadjusted (OR 2.29, 95% CI 1.85-2.84, p<0.01, I2=61.34%) and adjusted odds (aOR 2.01, 95%CI 1.62-2.50, p<0.01, I2=52.81 %) of post-TAVR mortality (Fig. 1). Subgroup analysis revealed elevated mortality risk in both retrospective (OR 1.86, 95% CI: 1.33-2.60, p<0.01) and prospective (OR 2.21, 95% CI: 1.62-3.01, p<0.01) studies (Fig. 1). Furthermore, increased mortality risk persisted during both short-term (less than 2 years; OR 1.86, 95% CI: 1.33-2.60, p<0.01) and long-term (more than 2 years; OR 2.21, 95% CI: 1.62-3.01,p<0.01) follow-up (Fig. 1). Leave-one out sensitivity analysis confirmed the robustness of findings.

Conclusion:
This meta-analysis provides compelling evidence that elevated pre-procedural levels of hs-cTn serve as a significant predictor of post-TAVR 1-year mortality.
Abstract 14772: Subcutaneous Implantable Cardioverter Defibrillator Extractions: A Single-Healthcare System Analysis of Incidence and Indications
Authors: Gangadharan Arati A , Peigh Graham , Sink Joshua , Arif Mariam , Carneiro Herman , Elsayed Mahmoud , Gay Hawkins , Gao Xu , Patil Kaustubha , Chicos Alexandru , Kim Susan S , Lin Albert C , Arora Rishi , Pfenniger Anna , Passman Rod S , Knight Bradley P , Verma Nishant
Published: December 2023

Introduction:
The subcutaneous implantable cardioverter defibrillator (SICD) serves as an alternative to traditional transvenous implantable cardioverter defibrillators in patients who meet criteria for ICD implantation without concurrent need for cardiac pacing. Data on SICD extraction is limited. This study examines the rates of SICD extraction.

Methods:
A retrospective study of all patients who underwent SICD implantation between 2010 and 2022 at a single healthcare system was performed. The primary endpoint was rate of SICD extraction.

Results:
A total of 402 patients (67.4% male; 48.5 ± 14.4 years old) underwent SICD implantation. Of these, 158 (39.3%) were for primary prevention in patients with heart failure with reduced ejection fraction, 125 (31.1%) for secondary prevention of ventricular tachyarrhythmias, and 69 (17.2%) for primary prevention in patients with hypertrophic cardiomyopathy with high-risk features. 29 (7.2%) patients (86.2% male; 51.5 ±12.9 years old) underwent SICD extraction during a mean follow up of 4.5 years. The median length of time between implant and explant was 49.1 [26.7-64.9] months. The most common indications for SICD extraction were need for pacing (17.2%), infection (17.2%), inappropriate shocks due to oversensing (13.8%), and lead failure (10.3%). There were no significant differences in average age, sex, or comorbidity profile between those who did and did not necessitate SICD extraction (extraction: 51.5 ± 12.9 years; no extraction: 48.4 ± 14.5 years; p=0.26) (Table).

Conclusions:
In appropriately selected patients undergoing implantation of the SICD, the likelihood of needing the device extracted was low at only 7.2% over 4.5 years, with the most common indications for extraction being need for pacing and infection. Further work must be done to determine whether these results regarding rates of, and indications for, SICD extractions are transferrable to other health systems.
Abstract 14782: Pre- and Post-Hemodialysis Differences in Heart Failure Diagnosis by Current Heart Failure Guidelines in Patients With End-Stage Renal Disease
Authors: Bong Joon Kim
Published: December 2023

Introduction:
Patients with end-stage renal disease (ESRD) who are on hemodialysis (HD) have reduced vascular compliance and are likely to develop heart failure (HF).

Hypothesis:
This study estimated pre- and post-HD in ESRD HF diagnosis prevalence using the current guidelines.

Methods:
We prospectively investigated ESRD patients on HD using echocardiography between pre and post HD. We used structural or functional abnormality criteria of 2021 ESC guideline of HF

Results:
A total of 54 patients were enrolled. The mean age was 62.6 years and 40.1% were male. Forty-five patients (83.3%) had hypertension, 28 (51.9%) had diabetes, 20 (37.0%) had ischemic heart disease. Mean NT-pro BNP level was 11959.9pg/dL. The mean ideal body weight was 59.3kg, mean HD time was 237.4 minutes, and mean real filtration was 2.8 kg. The mean LVEF was 62.4% and mean LVEDD was 52.0 mm in pre-HD. Post-HD echocardiography showed significantly lower LAVI (33.3 ± 15.9 vs. 40.6 ± 17.1 ml/m
2
, p=0.030), TR jet V (2.5 ± 0.4 vs. 2.8 ± 0.4 m/s, p<0.001), and RVSP (32.1 ± 10.3 vs. 38.4 ± 11.6 mmHg, p=0.005) compared with pre-HD. There was no difference in LVEF, E/E’ ratio, or LV GLS. A total of 88.9% for pre-HD and 66.7% for post-HD had at least structural or functional abnormalities according to recent HF guidelines (p=0.007).

Conclusions:
Our data show that post-HD echocardiography showed significantly reduced LAVI, TR jet V and RVSP compared to pre-HD. The difference of prevalence of HF was 22.2% between pre- and post- HD.
Abstract 14789: Atrial Anatomical Variations Between Atrial Fibrillation Patients Compared to Other Subjects Without Atrial Fibrillation
Authors: Abazid Rami , Romsa Jonathan , Warrington James , Akincioglu Cigdem , Tzemos Nikolaos , Vezina William , Khan Habib
Published: December 2023

Introduction:
In this study, we evaluated the anatomical atrial variations using gated cardiac computed tomography (CCT) between patients with and without atrial fibrillation (AF).

Hypothesis:
The aim of the study is to evaluate if there are specific anatomical characteristics that are associated with poor clinical outcomes following ablation in patients with AF.

Methods:
We retrospectively included 502 CCT scans of patients with AF prior to their pulmonary vein isolation procedure, and 1058 CCT scans of patients without AF performed to evaluate pulmonary vein anatomy and to rule out coronary artery disease between 2014 to 2017. Anatomical variations of the atria and interatrial septum included the Bachman bundle shunt (BBS - defined as a vascular channel crossing between the atria through the Bachman bundle), and atrial diverticulae.

Results:
Five-hundred and two patients with AF were older (67±14 vs. 63±13 years, P = 0.039), had a higher prevalence of diabetes mellitus (24.4% vs 14.7%, p = 0.006), and cerebrovascular disease (3.8% vs. 0.9%, p = 0.044) compared to patients without AF. Furthermore, CCTs analysis of AF patients demonstrated a significantly higher prevalence of BBS: (11% vs 4.1%, p <0.0001, left atrial diverticula (19% vs 7.7%), p <0.0001, and right atrial diverticula (9.8% vs 2.1%), P <0.0001 compared to patients without AF.

Conclusions:
This study is the first to analyze BBS and atrial diverticular prevalence in patients using CCT. We found that patients with AF are associated with a higher prevalence of structural atrial abnormalities including BBS, left and right atrial diverticula in comparison to individuals with no previous history of AF. Whether these anatomical variations influence AF incidence or AF recurrence after catheter ablation is yet to be determined.
Abstract 14799: Temporal Trends and In-Hospital Outcomes of Patients Undergoing Leadless Pacemaker Placement: Highlights From National Inpatient Sample 2016-2020
Authors: Desai Spandan , Roma Nicholas , Ferraro Bruce , Shah Kashyap , Plamenac Jovan
Published: December 2023

Introduction:
Leadless pacemakers (LPM) were introduced to address rates of pocket and lead-related complications associated with transvenous pacemakers (TPM) and to improve clinical outcomes in those who may be at high risk for TPM placement. Limited data exists on in-hospital outcomes and temporal trends of LPM placement.

Methods:
National Inpatient Sample 2016-2020 was used to query pacemaker (PM) placements and these were grouped into LPM and TPM cases using appropriate ICD procedure codes. Logistic regression was used to compare baseline characteristics and in-hospital outcomes.

Results:
740,240 PM placements were observed between 2016 and 2020, with 3.9% (29,015) LPM cases and 96.1% (711,225) TPM cases. As shown in Table 1, there was an increasing temporal trend in LPM placement from 2016 with an overall stable trend in TPM during the same time. The LPM group had a higher proportion of cases that underwent extraction of an old pacemaker (8.9% -vs- 6.9%, p=0.004). A majority of procedures in both groups were performed in the Southern United States and predominantly in large bedsize, urban teaching hospital systems. As shown in Table 2, LPM group had higher proportions of atrial fibrillation, CKD (stage 3 or greater), and ESRD. Length of stay (LOS, 9.7 -vs- 5.9 days) and overall mortality (5.0% -vs- 1.5%, p=0.001) were also higher in the LPM group.

Conclusions:
There has been a significant increase in LPM placement from 2016 through 2020 as seen with an increasing temporal trend. Use of LPM in medically complex cases or in cases that are high risk for TPM placement continues to increase. Further research needs to be performed to analyze long-term outcomes in this group.
Abstract 14815: Sex Differences in Transcatheter Aortic Valve Replacement Outcomes Among Patients With Bicuspid Aortic Stenosis: Insights From the National In-Patient Sample
Authors: Rivera Frederick B , Redula Sonny , Liston Mara Bernadette , Ong Erika , Bantayan Nathan Ross , Choi Sarang , Sharma Vikram , Kaur Gurleen , Collado Fareed Moses M , Volgman Annabelle S , Mamas Mamas
Published: December 2023

Introduction:
Studies have shown higher in-hospital mortality and complications among women who underwent transcatheter aortic valve replacement (TAVR) compared to men. However, most of these studies excluded patients with bicuspid aortic stenosis (BAS). Our aim is to determine if there are sex differences in outcomes among patients with bicuspid AS who underwent TAVR.

Methods:
This analysis was performed using the National Inpatient Sample (NIS) database. Multivariable regression analyses were performed to adjust for anticipated confounders for in-hospital outcomes. The main multivariable model (model A) included variables on patient demographics and comorbidities. Model B further adjusted for history of myocardial infarction (MI), prior percutaneous coronary intervention (PCI), and prior coronary artery bypass grafting (CABG). The main outcome is in-hospital mortality. (

See figure 1B)

Results:
More TAVR were performed in men (61.1%) than women (38.9%). Men were more likely to have coronary artery disease, carotid artery disease, and peripheral vascular disease.

(See table 1)

There was no difference in in-hospital mortality between sexes (1.5 versus 2.4, adjusted odds ratio (aOR) 1.521, 95% confidence interval (CI) 0.523 - 4.424; p< 0.44. Furthermore, there was no sex difference in secondary outcomes.

Conclusions:
A significantly higher proportion of men undergo the procedure as compared to women. There was no sex difference in in-hospital mortality and other secondary outcomes. More research is needed to address this sex gap in the performance of TAVR in BAS.
Abstract 14853: Effects of Yearlong High Intensity Aerobic Exercise on Reducing Left Atrial Epicardial Adipose Tissue
Authors: Noorbaksh Ali A , Shankar Aditi , MacNamara James P , Hearon Christopher M , Levine Benjamin D , Sarma Satyam
Published: December 2023

Background:
Left atrial epicardial adipose tissue (LA EAT) is often elevated in patients with heart failure and has been linked to abnormal atrial function and increased risk for atrial fibrillation. Whether LA EAT is potentially modifiable is unknown. We tested the hypothesis that one year of high intensity interval training (HIIT) would reduce LA EAT area and in turn be associated with improved atrial function in an obese cohort at risk for developing heart failure with preserved ejection fraction (HFpEF).

Methods:
Middle-aged obese adults (n = 80, age 40-55 yrs) enriched for increased HFpEF risk (N-terminal pro-B-type natriuretic peptide >40 pg/mL or high-sensitivity cardiac troponin T >0.6 pg/mL; visceral fat >2kg) were randomized to one year of HIIT or attention control. Outcome variables included LA EAT area and LA strain. LA EAT area was quantified through tracings of anterior, posterior, and lateral EAT depots in long axis views on cardiac MRI. LA strain was measured with MRI feature tracking as reservoir strain during left ventricular (LV) systole, conduit strain during early LV diastole, and contractile strain during late LV diastole.

Results:
Fifty-three participants completed the study. There was no difference in LA EAT area after one year in either the HIIT group (n = 26) or controls (n = 27); difference in mean = -0.17 cm
2
, 95% CI = -0.93 to 0.59, p = 0.66. However, amongst all participants, reduction in LA EAT was associated with improvement in LA reservoir strain (r = -0.50, 95% CI = -0.68 to -0.26, p < 0.001) and LA conduit strain (r = 0.51, 95% CI = 0.27 to 0.68, p < 0.001) but not LA contractile strain (r = 0.15, 95% CI = -0.13 to 0.40, p = 0.298).

Conclusions:
One year of HIIT did not reduce LA EAT in at-risk obese patients. However, regardless of assignment, decreased LA EAT was associated with improved LA reservoir and conduit strain, suggesting efforts to reduce LA EAT may improve LA function in at-risk obese patients.