bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 9383: Full versus Limited Transesophageal Echocardiography at the Time of Cardioversion for Atrial Fibrillation
Authors: Mohammad Khan O , Alexander Steven A
Published: June 2023

Introduction:
Transesophageal echocardiography (TEE) is frequently used to evaluate the left atrial appendage (LAA) prior to direct-current cardioversion (DCC) for atrial fibrillation (AF). Clinically relevant findings may be discovered prior to DCC. The optimal TEE study protocol at the time of DCC is unknown.

Methods:
One-hundred and fifty patients undergoing TEE-guided DCC for AF were retrospectively analyzed. Patients were separated into two groups based on the type of study performed. Comprehensive studies were defined as full TEEs (F-TEE). Studies focused on the LAA were defined as limited TEEs (L-TEE). The TEE findings between both groups were compared.

Results:
Among 150 patients included in the study (mean age, 66.9 ± 14.3 years; 31% female), 81 (54%) had an F-TEE and 69 (46%) had an L-TEE. Abnormal findings were significantly higher in the F-TEE group compared with the L-TEE group (76.5% versus 47.8%; P<0.005). In patients with a prior study, a new finding was observed more often in the F-TEE versus L-TEE group (56.5% versus 22.0%; P<0.005). In patients with a prior study performed within the previous 2 months, a new finding was observed in 55.3% versus 28.1% (P=0.022). F-TEE took longer to perform compared to L-TEE (7.9 ± 3.3 versus 4.3 ± 3.8 minutes; P<0.005).

Conclusions:
Among patients undergoing TEE-guided DCC for AF, F-TEE reported significantly more cardiovascular pathology when compared to L-TEE. Among patients with prior echocardiographic studies, F-TEE reported significantly more new findings, regardless of whether the prior study was recent or remote. We believe our findings offer a convincing argument to adopt an F-TEE protocol for studies performed pre-DCC.
Abstract 9407: Long-Term Outcomes of Hospitalized Acute Myocarditis: A Korean Nationwide Data in the Pre-COVID-19 Era
Authors: Kim Mi-jeong , Jung Hae-Ok , Kim Hoseob , Bae Yoonjong , Jeon Doo-Soo , Kim Kyung Ahn , Lee Soyoung , Kim Soohyun , Park Soyoon
Published: June 2023

Introduction:
Acute myocarditis is extremely heterogenous in causal agents, clinical courses, and geographic regions. There is little long-term outcomes data for acute myocarditis prior to the COVID-19 pandemic.

Hypothesis:
The clinical profile of acute myocarditis would differ according to age at presentation.

Methods:
A retrospective nationwide cohort study was performed. All patients aged 20-79 who were hospitalized for acute myocarditis without underlying cardiac diseases from 2006 to 2018 in Korea. Complicated phenotype was defined as requiring hemodynamic or major organ support. Over 10 years, all-cause mortality and acute myocarditis-driven excess mortality were evaluated according to young-adult (20-39 years), mid-life (40-59 years), and older-adult (60-79 years) age groups.

Results:
Among 2988 patients (mean age 51.0 years), 362 (12.1%) were of complicated phenotype. All-cause death at 30 days occurred in 40 (4.7%), 52 (4.8%), and 105 (10.0%) patients in the young-adult, mid-life, and older adult groups, respectively (Figure A). Most short-term deaths occurred within 37 days of admission, primarily in the complicated phenotype. However, higher excess mortality compared to the age- and sex-matched general population remained over the 10-year follow-up even in younger patients with non-complicated phenotypes (Figure B).

Conclusions:
In patients with de novo acute hospitalized myocarditis, short-term mortality is high both in young and older adults, particularly those with advanced age, non-cardiac comorbidities, and severe clinical presentation. Furthermore, long-term excess mortality remains high over 10 years after index hospitalization. A cardiac monitoring strategy should be discussed for post-myocarditis patients against the long-term risk.
Abstract 9459: Bariatric Surgery Improves Mortality in Patients With Heart Failure
Authors: Cordova Andres M , Morales Mejia Ana M , Chaudhuri Debanik
Published: June 2023

Introduction:
Bariatric surgery has been associated with decreased adverse cardiovascular outcomes. There is a paucity of data regarding long-term outcomes in patients with heart failure who underwent bariatric surgery.

Hypothesis:
Bariatric surgery is associated with better long-term outcomes in patients with heart failure and BMI≥40.

Methods:
Using ICD-10 codes, we identified patients with heart failure and BMI≥40 from 2016 to 2021 by using the TriNetx diamond network which includes data from ambulatory and primary care electronic medical records, medical claims from claims clearinghouses, and patient medication data from pharmacy claims around the USA. The patient population was divided in 2 groups, those who underwent a bariatric surgery procedure versus those who did not. Subgroup analysis of patients with systolic and diastolic heart failure was also performed. Propensity score matching was used to equilibrate for approximately 90 variables. The outcomes were measured from 3 months up to 5 years after the index event.

Results:
A total of 2,896 patients were included in each cohort, 63% were females. Patients with heart failure and BMI ≥ 40 kg/m2 that underwent bariatric surgery had approximately 67% lower likelihood of mortality (OR 0.336, P<0.0001), 50% lower incidence of atrial fibrillation (OR 0.504, P<0.0001), 45% less ventricular tachycardia (OR0.556, P0.0014), 43% less AMI (OR 0.578, P 0.0148), and 30% less cerebral ischemia (OR 0.708, P0.043). On subgroup analysis, similar outcomes were seen in patients with systolic heart failure except for cerebral ischemia which did not have a significant association. In patients with diastolic heart failure, only mortality and atrial fibrillation had lower incidences after bariatric surgery.

Conclusions:
Bariatric surgery is associated with decreased mortality and cardiovascular outcomes in patients with heart failure and BMI≥40. Prospective and/or randomized studies are required to prove these results.
Abstract 9474: Trim35-Mediated Ubiquitination and Degradation of Nuclear PKM2 is Sufficient to Promote Heart Failure
Authors: Lorenzana Carrillo Maria A , Gopal Keshav , Byrne Nikole , Tejay Saymon , Saleme Bruno , Das Subhash , Zhang Yongneng , Haromy Alois S , Eaton Farah , Mendiola Pla Michelle , Bowles Dawn E , Dyck Jason R , Ussher John R , Michelakis Evangelos D , Sutendra Gopinath
Published: June 2023

Introduction:
Pyruvate Kinase M2 (PKM2) is a glycolytic enzyme that can translocate to the nucleus to regulate different transcription factors (TF) in different tissues or pathologic states. Although its function has been studied extensively in cancer, its biologic role in the heart and specifically terminally differentiated adult cardiomyocytes remains unresolved.

Hypothesis:
PKM2 may be critical in regulating cardiomyocyte(CM)-specific TF important for cardiac survival.

Methods:
Transverse aortic constriction (TAC) banding model was used to assess the levels and modifications of PKM2 during heart failure (HF). CM-specific PKM2-deficient and CM-specific Trim35 overexpressing(OE) mice were generated to evaluate the role of PKM2/Trim35 in adult CM. Human Dilated Left Ventricle biopsies were used to translate mechanistic findings into a clinical setting.

Results:
Here we show that nuclear PKM2 (
S37
P-PKM2) in CM interacts with several pro-survival or pro-apoptotic TF, including Gata-4, Gata-6, and p53. CM-specific PKM2-deficient mice developed age-dependent dilated cardiac dysfunction and had decreased levels of Gata-4/6, but increased levels of p53, compared to control Cre+ hearts. Mechanistically, we found that nuclear PKM2 can prevent caspase-1 dependent cleavage Gata-4/Gata-6, while also providing a platform for Mdm2-mediated ubiquitination of p53. In a preclinical HF model, nuclear PKM2, along with Gata-4/6 levels decreased, but p53 levels increased (compared to sham controls). Loss of nuclear PKM2 was ubiquitination-dependent and associated with the induction of the E3 ubiquitin-ligase TRIM35. CM-specific Trim35 OE mice had decreased
S37
P-PKM2 and GATA-4/6, along with increased p53 levels (compared to littermate controls) and had similar cardiac dysfunction to CM-specific PKM2-deficient mice. In a well-characterized cohort of patients with dilated left ventricles, we found a significant increase in TRIM35 levels that was associated with a decrease in
S37
P-PKM2, Gata-4/6 levels, but an increase in p53 levels, compared to non-failing ventricles.

Conclusion:
This study provides insight into a previously unrecognized biologic role for PKM2 in providing a molecular platform for TF essential for preserving cardiac survival.
Abstract 9496: Association Between Oral Anticoagulant Type and Hospital Readmission Rates Following Myocardial Infarction With Percutaneous Coronary Intervention in Patients With Nonvalvular Atrial Fibrillation
Authors: Desai Nihar , Botros Afraim , Panda Ankita , Xia Qian , Huff Keith
Published: June 2023

Introduction:
Clinical trials have shown improved outcomes with direct-acting oral anticoagulant (DOAC)- vs. warfarin-based regimens in patients with atrial fibrillation (AF) with acute coronary syndrome and/or undergoing percutaneous coronary intervention (PCI). This study investigated the impact of anticoagulant type on hospital readmission rates following a myocardial infarction (MI) managed with PCI in patients with nonvalvular AF (NVAF) in the real world.

Methods:
This was a retrospective, observational study using data from two US claims databases, Optum
®
Research and PharMetrics
®
Plus. Patients with NVAF who were hospitalized for MI, underwent PCI between January 1, 2014 and December 31, 2020, and initiated treatment with warfarin or a DOAC (dabigatran, rivaroxaban, apixaban, or edoxaban) exclusively during the index hospitalization or ≤365 days after discharge were included. Once identified, patients were followed for up to 12 months post-discharge. Hospital readmission rates at 30, 90, 180, and 365 days were compared for DOACs vs warfarin using multivariate Cox proportional hazards modeling.

Results:
The Optum cohort included 2647 patients (1997 DOAC, 650 warfarin) and the PharMetrics cohort included 2056 (1468 DOAC, 588 warfarin). In both cohorts, unadjusted all-cause, stroke/systemic embolism (SE)-related, and bleed-related hospital readmission rates were lower for DOACs vs warfarin at all timepoints. Regression analysis showed a significantly lower risk of hospital readmission with DOACs vs warfarin (
Table
).

Conclusions:
Real-world data from two large claims databases demonstrated that post-hospitalization DOAC treatment was associated with lower hospital readmission rates than warfarin treatment in patients with NVAF who were hospitalized for MI and underwent PCI. These results thus demonstrate the value of DOAC treatment for these patients.
Abstract 9525: Changes in Managing Post-Stroke Challenges After Receiving a Self-Management Programme: A Qualitative Study
Authors: Lo Suzanne H , Chau Janita P , Iu Issac Hok Lai
Published: June 2023

Introduction:
Supporting self-management is essential to improving health outcomes after stroke. More evidence on the stroke survivors’ experiences and perceived usefulness of the self-management interventions are needed to provide better support.

Purpose:
This study was aimed to explore stroke survivors’ experiences of attending an 8-week programme which consisted of four home visits and five follow-up phone calls and delivered by a collaborative team of nurses and trained lay volunteers.

Methods:
A qualitative study was conducted with a convenience sample of the survivors who had received the programme. After completing the programme, the survivors were interviewed individually by phone using a semi-structured interview guide about their changes in perceiving and responding to post-stroke physical and psychosocial challenges. Suggestions to improve their experience of participation were collected. Interview data were transcribed verbatim and analysed thematically.

Results:
Thirty stroke survivors (mean age=60 years, SD=11.74) were interviewed. Most of them were male (60%), married (63.3%) and had a first-ever ischaemic stroke (50%). The mean duration of onset after stroke was 5.63 years (SD=3.12). About 63% of them walked unaided or with a stick. Four (13.3%) had mild dysphasia. Four themes were derived: developed short-term goals with lifestyle-integrated action plans; resumed social activities or work; increased satisfaction with life and sense of being cared for; more effective communication and relief of negative emotions; increased adoption of new and creative strategies to improve limb functions. Suggestions for improving the programme included longer duration, more home visits, earlier support upon discharge from the hospital, meetings with other survivors for mutual support while working towards the goals, and more structured follow-up phone calls.

Conclusions:
The self-management programme was found helpful in improving the survivors’ confidence and performance of self-management behaviours. Making the programme available upon discharge, and extending its duration with more home visits, group sessions and structured phone calls would build stronger self-management capabilities in survivors.
Abstract 9537: Preliminary Analysis of the Impact of IV Iron Repletion in Patients With Iron Deficiency Anemia and Chronic Thromboembolic Pulmonary Hypertension Undergoing Pulmonary Thromboendarterectomy
Authors: Lee Madeline , Lin Allan , Pietrowicz Rylie , Maruthi Rohit , Vaidya Anjali , Oliveros Estefania , Forfia Paul R
Published: June 2023

Introduction:
Iron deficiency anemia (IDA) is associated with worse functional class, shorter 6-minute walk distance (6MWD), and higher mortality in heart failure. The associations of IDA with chronic thromboembolic pulmonary hypertension (CTEPH) have not been established.

Methods:
Retrospective chart review of 95 patients with CTEPH who underwent pulmonary thromboendarterectomy (PTE) and had iron studies. We determined the prevalence of IDA and the impact of IV iron repletion in the perioperative period.

Results:
Of the 95 patients, the mean age was 56 years, 55% were female, 52% were White, and 28% were Black. Thirteen (13.6%) had IDA and received IV iron perioperatively when admitted for PTE. Those who had IDA were younger (50.3 vs 57.7 years, p=0.09) and female (69.2%). Of the females, 3 (33.3%) had uterine fibroids. Baseline hemoglobin was lower in the group requiring IV iron (10.5 vs 13.1 g/dL, p=0.0004). The patients received 1-5 days of IV iron. Cardiac index (CI) pre-PTE was not different between IDA versus non-IDA groups (2.4 vs 2.2 L/min, p=0.35) and the PVR was non-statically different (8.4 vs. 7.2 WU, p=0.63). Post-PTE, CI were normal in both groups (2.4 vs 2.7 L/min, p=0.03). The IDA group had worse baseline NYHA functional class (75% class III or higher, p=0.66) than the non IDA group (90% class II or lower, p=0.66). Those with IDA had lower baseline 6MWD of 277 vs 343 meters (p=0.14; Fig 1), despite a similar baseline PVR and CI. Post PTE and after IV iron repletion, 6MWD were similar between the IDA and non IDA group 385 vs 348 meters; p=0.75, respectively.

Conclusion:
Our results suggest younger and female CTEPH patients may have a higher incidence of IDA. IDA contributes to the functional capacity of patients with precapillary CTEPH. There is a trend towards improvement of the functional impairment in the CTEPH patients when they receive IV iron repletion in the perioperative period of PTE, in groups that have similar baseline CI and PVR, and normal CI in the post-PTE period.
Abstract 9539: Risk of Earlier Atherosclerotic Cardiovascular Disease in Women With Low Bone Mineral Density
Authors: Park Jiesuck , Kim Kyoung Min , Yoon Yeonyee E , Hwang In-chang , Cho Goo-Yeong
Published: June 2023

Background:
The potential association between lower bone mineral density (BMD) and atherosclerotic cardiovascular disease (ASCVD) has been suggested in women. We investigated whether the association between low BMD and ASCVD differs according to the age of ASCVD occurrence.

Methods:
We retrospectively analyzed 7,932 women aged 50-65 years who underwent dual-energy X-ray absorptiometry to measure total hip BMD. The primary outcome of interest was ASCVD, defined as a composite of ASCVD death, myocardial infarction, and ischemic stroke. Participants were classified into no event (n=7,803), early ASCVD (occured before 70 years of age) (n=97), and late ASCVD (occured at or after 70 years of age) (n=32) groups. The association of low BMD with early and late ASCVD was estimated using multivariate Cox hazard modeling after adjustment for clinical risk factors (age, body mass index, hypertension, diabetes, hyperlipidemia, current smoking, and previous fracture).

Results:
The median age increased across no event, early ASCVD, and late ASCVD groups (58, 60, and 63 years, respectively). However, the estimated BMD T-score at the age of 65 years was lowest in the early ASCVD group (median -0.9, -1.1, and -0.5, respectively). Lower BMD was an independent predictor for early ASCVD (adjusted hazard ratio [HR]: 1.34 per 1-SD decrease in T-score, 95% confidence interval [CI] 1.08-1.67), but not late ASCVD (adjusted HR: 0.88, 95% CI 0.60-1.30) (Figure). The inverse trend between early ASCVD risk and BMD T-score was consistent regardless of the number of accompanied clinical risk factors.

Conclusions:
Low BMD is an independent predictor for earlier ASCVD occurrence in women. BMD evaluation can provide prognostic benefit for risk stratification for earlier ASCVD occurrence.
Abstract 9547: Demographic Differences in Patients With Frequent PVCs and Cardiomyopathy in the General Population Receiving Ambulatory Holter Monitoring
Authors: Huizar Jose F , Sima Adam , Comstock Connor S , Kaszala Karoly , TAN ALEX Y , Frankel David S , Marchlinski Francis E , Kowalski Marcin , Sharma Parikshit , GERSTENFELD Edward , Vaseghi Marmar , Shivkumar Kalyanam , Malhotra Rohit , Morillo Carlos A , Ellenbogen Kenneth A
Published: June 2023

Introduction:
A high burden of premature ventricular contractions (PVCs) has been associated with the development of cardiomyopathy (CM) and heart failure. However, the prevalence of high PVC burden and cardiomyopathy (CM) remain unclear.

Hypothesis:
The prevalence of high PVC burden (>5%) is underestimated in patients receiving Holter monitors and those with CM (LVEF <50%).

Methods:
A prospective multicenter clinical study of consecutive patients undergoing ambulatory Holter monitors (24 hours up to 2-weeks), between July 2018 through June 2020 were reviewed. Demographic data, PVC burden and LV function were collected within 6 months of Holter placement.

Results:
A total of 8 centers across the US provided a total of 6,808 patients with ambulatory Holter monitors. Four and 5% of patients undergoing Holter monitors had a PVC burden of 6-10% and >10%, respectively. A total of 3,938 patients had assessment of LVEF within 6 months of Holter, of which 634 (16%) had CM and 173 (4%) had both CM and PVCs > 5%. Males were more likely to have had LVEF assessment than females (58% vs. 55%, P=0.013). Table summarizes demographics in the overall population based on PVC burden and presence of CM. High PVC burden (>5%) was more prevalent in older, male, and White patients. In an ordinal logistic regression to assess PVC burden with gender separately for LVEF < or > 50%, females were found to have a higher PVC burden in the population with preserved LVEF (OR=1.59, 95% CI: 1.13, 2.22) but not with CM (LVEF < 50%, OR=1.13, 95% CI=0.97, 1.32). Females had a lower prevalence of high PVC burden (>5%) than males (7% vs. 11%; p<0.001), including among those with CM (23% vs. 29%, p=0.1).

Conclusions:
High PVC burden and CM are quite prevalent in the population undergoing Holter monitors. Older age is associated with higher PVC burden but no age difference is present between different PVC burdens in patients with CM. Females have a lower prevalence of high PVC burden (>5%) and combined high PVC burden and CM than males.
Abstract 9548: Dual Energy Computed Tomography Perfusion Mapping of Coronary to Pulmonary Collaterals in Chronic Thromboembolic Pulmonary Hypertension
Authors: Goyal Ansh , Cuttica Michael , Flaherty James D , Malaisrie Christopher C , Mylvaganam Ruben
Published: June 2023

Introduction:
Chronic thromboembolic pulmonary hypertension (CTEPH) is classified as group 4 pulmonary hypertension where unresolved thromboembolic disease obstructs the pulmonary artery. The resultant lung ischemia commonly leads to bronchopulmonary collateralization thought to lower pulmonary vascular resistance and reduce mortality. Here, we present a rare presentation of coronary-pulmonary collaterals in a 65-year-old former 40-pack year smoker with CTEPH, COPD requiring oxygen, AF, and DHF.

Results:
Dual-energy computed tomography (DECT) showed complete occlusion of the proximal right pulmonary artery. However, perfused blood volume (PBV) mapping of the DECT study revealed areas of the right lung that were still minimally perfused
(Figure 1A, B).
Pulmonary angiography confirmed occlusion of the right pulmonary artery
(1C)
. Subsequent coronary angiography revealed the presence of coronary to pulmonary collaterals that were providing limited perfusion to the right pulmonary circulation from the left circumflex artery
(1D)
. The patient underwent pulmonary thromboendarterectomy with removal of the clot en bloc without complication
(1E)
. Post-surgery DECT confirmed restoration of pulmonary arterial circulation and catheterization revealed an excellent hemodynamic response to surgery
(1F, G)
.

Conclusions:
DECT-derived PBV revealed significant perfusion to a proximally obstructed lung, hastening the discovery of rarely documented coronary-pulmonary artery collaterals via coronary angiography. We uniquely visualize via perfusion mapping that the collaterals provide an alternate vascular supply distal to the chronic pulmonary arterial obstruction until thromboendarterectomy can conclusively treat the occlusion. The presence of coronary-pulmonary collaterals may share similar pathophysiology to bronchial-pulmonary collaterals and be a positive prognosticator for robust post-operative hemodynamic improvement in CTEPH.
Abstract 9556: From Low Volume to High Volume: Successful Reduction in Major Complications While Building Transvenous Lead Extraction Center Volume
Authors: Stout Kara , Sood Eshan , Schleifer John , Khan Faris , Naksuk Niyada , Haynatzki Gleb , Pratt David N , Erickson Christopher C , Moulton Michael J , Anderson Daniel R
Published: June 2023

Introduction:
Transvenous lead extraction (TLE) is associated with better outcomes in high-volume (HiV, >30 TLE/year) than low-volume centers. Little data exist regarding transitioning to a HiV TLE center. We examined the impact of strategic interventions at a tertiary care center transitioning to a HiV TLE center.

Hypothesis:
Systematic interventions to increase TLE volume and quality are expected to decrease the rate of major complications without adversely affecting procedural success rates.

Methods:
Consecutive patients undergoing TLE with leads >1 year post implantation from 2012-2021 were reviewed. The primary endpoints were TLE success and major complications including TLE-related mortality, vascular laceration, pericardial effusion, and emergent cardiothoracic surgery. Outcomes were compared between TLE completed in 2012-2018 prior to the intervention (n=125) and TLE after intervention 2019-2021 (n=127).

Results:
There were 252 consecutive TLE procedures included involving 398 leads. Strategic interventions were implemented in 2018 (Figure). Annual mean TLE volume increased from 19.5 TLE (29.7 leads) to 42.4 TLE (69.7 leads). Baseline characteristics including age (62.4±14.7 vs. 61.9±17.4), gender (52.4% vs. 47.7% male), and infectious indications (33.6% vs. 35.4%) were similar (P>0.05 for all). With the transition to a HiV center, there was no significant change in complete procedural success (84.0% vs. 85.8%, P=0.73) and clinical success (94.4% vs. 96.1%, P=0.57). Major complications significantly decreased from 10/125 (8.0%) to 3/127 (2.4%) after the interventions in 2018 (P=0.049).

Conclusions:
Multidisciplinary improvements in pre-procedural risk stratification, scheduling, and technique resulted in a successful transition to a HiV TLE center with a reduction in major complications and a high procedural success rate.
Abstract 9574: Distribution of Anti-Factor Xa Activity Value, Prothrombin Time, and Activated Partial Thromboplastin Time in Patients Treated With Factor Xa Inhibitors
Authors: Ono Ryohei , Fukushima Kenichi , Takahashi Hidehisa , Hori Yasuhiko , Kobayashi Yoshio
Published: June 2023

Introduction:
The distribution of anti-factor Xa activity (AXA) values, prothrombin time (PT), and activated partial thromboplastin time (APTT) in patients administered each factor Xa (FXa) inhibitors (apixaban, edoxaban, and rivaroxaban) has not fully been assessed.

Purpose:
To clarify the distribution of AXA, PT, and APTT in patients taking FXa inhibitors.

Methods:
Trough and peak AXA values, PT, and APTT were measured in 85 patients taking apixaban, 105 patients taking edoxaban, and 27 patients taking rivaroxaban. The patients were further divided into three groups based on the dosage.

Results:
At trough time of apixaban, the AXA values in patients administered 20 mg were significantly higher than those administered 5 mg or 10 mg (P < 0.001). PT in patients administered 20 mg were significantly higher than those administered 5 mg or 10 mg (P = 0.006). At peak time, the AXA values in patients administered 20 mg were significantly higher than those administered 5 mg or 10 mg (P < 0.001). PT in patients administered 20 mg was significantly higher than those administered 5 mg or 10 mg (P < 0.001). APTT in patients administered 20 mg was significantly higher than those administered 5 mg or 10 mg (P < 0.001). At peak time of edoxaban, the AXA values in patients administered 60 mg were significantly higher than those administered 15 mg or 30 mg (P < 0.001). PT in patients administered 60 mg were significantly higher than those administered 15 mg or 30 mg (P = 0.006). APTT in patients administered 60 mg was significantly higher than those administered 30 mg (P = 0.003). At trough time of rivaroxaban, the AXA values in patients administered 30 mg were significantly higher than those administered 10 mg or 15 mg (P = 0.001). At peak time, AXA values in patients administered 30 mg were significantly higher than those administered 15 mg (P = 0.028).

Conclusion:
This study determined the distribution of AXA, PT, and APTT in patients administered apixaban, edoxaban, and rivaroxaban.
Abstract 9590: Synergistic Effect of Lipoprotein (a) and C-reactive Protein on Prognosis of Familial Hypercholesterolemia
Authors: Tada Hayato , Kojima Nobuko , Yamagami Kan , Nomura Akihiro , Nohara Atsushi , Usui Soichiro , Sakata Kenji , Fujino Noboru , Takamura Masayuki , Kawashiri Masa-aki
Published: June 2023

Background:
The synergistic effect of lipoprotein (a) [Lp(a)] and C-reactive protein (CRP) on major adverse cardiovascular events (MACE) among patients with familial hypercholesterolemia (FH) is unknown.

Objective:
This study aimed to investigate the relations between Lp(a) and CRP levels and MACE in patients with FH whose Lp(a) levels are elevated.

Methods:
We retrospectively investigated associations between genotypes and phenotypes, including low-density lipoprotein (LDL) cholesterol level and the occurrence of MACE among patients with FH (N = 786, male/female: 374/412). A Cox proportional hazard model was used to identify factors associated with MACE, adjusting for traditional risk factors. Patients with FH were divided into four groups, based on their Lp(a) and CRP levels, and assessed using Kaplan-Meier curves.

Results:
The median follow-up was 12.6 years (interquartile range [IQR], 9.5-17.9 years). During follow-up, 129 MACE were observed. Median Lp(a) and CRP levels were 21.4 (10.9-38.3) mg/dL and 0.20 (0.11-0.29) mg/dL, respectively. Under these conditions, natural log-transformed Lp(a) and CRP were not associated with MACE (hazard ratio [HR], 1.08; 95% confidence interval [CI], 0.91-1.25; P = 0.220; and HR, 1.12; CI, 0.96-1.28; P = 0.190, respectively). However, in Group 4, Lp(a) and CRP were significantly associated with MACE (HR, 2.44; CI, 1.42-3.46; P = 1.8 х 10
–7
).

Conclusion:
In patients with FH, Lp(a) was significantly associated with MACE only when the CRP level was elevated. Patients with FH whose Lp(a) and CRP levels are elevated should be treated aggressively.
Abstract 9685: Pharmacodynamic and Pharmacokinetic Profiles of Switching Between Cangrelor and Ticagrelor Following Ticagrelor Pre-Treatment: The SWAP-5 Study
Authors: Ortega-Paz Luis G. , Rollini Fabiana , Galli Mattia , Been Latonya , Ghanem Ghussan , shalhoub Awss , Ossi Tiffany , Rivas Andrea , Zhou Xuan , Rivas Rios Jose , Pineda Andres , Suryadevara Siva , Soffer Daniel , Zenni Martin , Angiolillo Dominick J , Franchi Francesco
Published: June 2023

Introduction:
The lack of drug-drug-interaction (DDI) with the use of ticagrelor in cangrelor-treated patients was demonstrated in studies in which ticagrelor was given at the time of initiation or during cangrelor infusion. However, many patients are pre-treated with ticagrelor and to date there is no data to rule out a DDI when ticagrelor is given prior to starting cangrelor.

Methods:
SWAP-5 is a randomized, double-blind, placebo-controlled, cross-over, pharmacokinetic (PK) and pharmacodynamic (PD) study conducted in 20 patients with coronary artery disease on aspirin (81mg/qd). Patients were pre-treated with a 180-mg ticagrelor loading dose (LD) and after 1 hour were randomized to placebo or cangrelor (bolus and infusion for 2 hours). Patients crossed over after 1-4 weeks of washout. PK analysis included plasma levels of ticagrelor and its active metabolite, and PD assessments included VerifyNow P2Y
12

reaction units (PRU), light transmittance aggregometry (LTA) with 20 μM ADP as agonist, and vasodilator-stimulated phosphoprotein (VASP), at baseline and 6 time points after ticagrelor LD.

Results:
Compared to placebo, adding cangrelor to patients pre-treated with ticagrelor resulted in a significant reduction in PRU at 30 min and 1 hour after starting infusion (
Figure
). At 2 hours after stopping the infusion, PRU was low and similar in both groups (16.9 vs. 12.6; mean difference: 4.3; 95% CI: -28.6 to 37.3), meeting the non-inferiority primary endpoint (pre-defined non-inferiority margin 45 PRU). LTA and VASP showed consistent findings. PK tracked PD findings with no difference between groups in plasma levels of ticagrelor and its metabolite (data not shown).

Conclusions:
SWAP-5 is the first PK/PD study supporting the feasibility of adding cangrelor in patients pre-treated with ticagrelor. This approach resulted in lower levels of platelet reactivity during cangrelor infusion with similar PK/PD profiles after stopping the infusion and no evidence of DDI.
Abstract 9710: Prevalence of Ekg Criteria Suggestive of Fabry’S Disease in Heart Failure Patients
Authors: Oredegbe Al-Ameen , White Casey , Mustafa Mohammed , Tawfellos George , Harris Erin , Torosoff Mikhail
Published: June 2023

Introduction:
Cardiac disease is the most important cause of morbidity and mortality in Fabry disease, an X-linked genetic condition caused by a defect in alpha-galactosidase A. Diagnosis of Fabry’s disease requires high index of suspicion and includes EKG assessment. Prevalence of EKG changes consistent with Fabry disease in patients admitted with heart failure has not been well investigated.

Methods:
Clinical, EKG and echocardiographic data were collected in 460 non-V paced consecutive CHF patients enrolled over 2 years in the Get with The Guidelines Heart failure (GWG-HF) registry at a single academic center. Fabry disease EKG features including shortened PR intervals, AV block, LVH criteria, QRS prolongation, left atrial enlargement (LAE), atrial fibrillation (AFIB), and bradycardia were recorded.

Results:
Of the studied criteria, shortened PR was noted in only 1.85% (6/324) of patients in sinus rhythm. Of the 460 non-V-paced rhythms patients, LVH was noted in 19% (87/460), QRS>120 ms in 20% (96/460), LAE in 21% (98/460), AFIB in 21% (100/460), and HR <60 bpm in 8% (37/460). Overall, 15% (70/460) of patients with non-V-paced rhythms had a combination of LVH/QRS and LAE/AFIB; this combination of ECG findings is potentially suggestive of Fabry disease. There were no significant differences in gender, age, BMI, BNP, GFR, or Hgb levels, degree LV dysfunction, histories of HTN, CAD, diabetes in these 70 patients vs. the rest of the cohort. However, patients with these criteria had significantly increased prevalence of HFrEF (55.7%, 39/70, vs. 42.8% in the rest of the cohort, 167/390, p=0.031). There was no difference in re-admission and/or mortality rates during the 70.7+/-25.2 month follow-up according to these ECG criteria.

Conclusions:
In our study of unselected patients with ascertained CHF diagnosis, many manifested with multiple EKG features associated with Fabry’s disease. While these patients had increased prevalence of HFrEF, there were no clinical or demographic characteristics separating these individuals from the rest of the cohort. Given poor prognosis and treatable nature of Fabry’s disease, these patients may benefit from additional clinical and laboratory evaluation directed at Fabry’s disease diagnosis
Abstract 9711: Association of Preoperative Body Mass Index With 30-Day Major Adverse Cardiovascular Events After Bariatric Surgery
Authors: Yang Yifeng , Liu Kan , Sun Yangbo
Published: June 2023

Introduction:
Despite bariatric surgery is the most effective and durable treatment for clinically morbid obesity, its association with intraoperative or 30-Day postoperative cardiovascular events after bariatric surgery is unclear.

Hypothesis:
To examine the association of preoperative body mass index (BMI) with adverse intraoperative or 30-day postoperative cardiovascular events after bariatric surgery.

Methods:
Our study extracted data from 785 321 patients who underwent bariatric surgery from 2015 to 2019 in the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP), which covers more than 90% of all bariatric surgery programs in the United States and Canada. The exposures were preoperative BMI and highest recorded preoperative BMI. The main outcomes were intraoperative or 30-day postoperative major adverse cardiovascular events (MACE).

Results:
Of the 785 321 patients (mean [SD] age 44.8 [11.8] years; 79.9% women), 1 541 patients suffered at least one MACE event intraoperative or 30-day postoperative bariatric surgery. Compared with patients with a preoperative BMI of 35.0 to 39.9, the multivariable-adjusted ORs (95% CIs) for intraoperative or 30-day postoperative MACE events for patients with preoperative BMI of 40.0 to 44.9, 45.0 to 49.9, 50.0 to 54.9, and 55.0 and greater were 1.05 (95% CI, 0.91-1.21), 1.19 (95% CI, 1.02-1.38), 1.28 (95% CI, 1.07-1.53), and 1.77 (95% CI, 1.50-2.09), respectively (
P
for trend < 0.001). Moreover, compared with highest recorded preoperative BMI of 35.0 to 39.9, the multivariable-adjusted ORs (95% CIs) for intraoperative or 30-day postoperative MACE events for patients with preoperative BMI of 40.0 to 44.9, 45.0 to 49.9, 50.0 to 54.9, and 55.0 and greater were 1.20 (95% CI, 1.01-1.41), 1.18 (95% CI, 0.99-1.40), 1.32 (95% CI, 1.09-1.59), and 1.76 (95% CI, 1.48-2.10), respectively (
P
for trend < 0.001).

Conclusions:
In this study, we found that higher preoperative BMI and higher highest recorded BMI were both associated with a higher risk of MACE events intraoperative or 30-day postoperative bariatric surgery. These findings may help improve perioperative cardiovascular optimization and provide evidence for future updates of clinical guidelines regarding bariatric surgery.
Abstract 9727: Reduced Bmpr2 Causes a Decrease in Foxf1 That Links Unrepaired DNA Damage to Persistent Pulmonary Hypertension
Authors: Isobe Sarasa , Nair Ramesh V , Moonen Jan-Renier A , Wang Lingli , Koerbelin Jakob , Snyder Michael , Rabinovitch Marlene
Published: June 2023

Introduction:
B
MPR2
mutation is the most common genetic cause of pulmonary arterial hypertension (PAH). Loss of
BMPR2
causes pulmonary arterial (PA) endothelial cell (EC) dysfunction and impairs EC-mediated suppression of smooth muscle cells proliferation. These are characteristic features of PAH vascular cells as is the presence of DNA damage that can be induced by oxidative stress. We previously showed that EC-
Bmpr2
-/-
mice have persistent pulmonary hypertension (PH) with reoxygenation after hypoxia. However, the role of DNA damage in causing persistent PH related to loss of BMPR2 and oxidative stress is unknown.

Hypothesis:
We hypothesize that loss of BMPR2 causes unrepaired DNA damage and persistent PH by altering the expression of genes that maintain EC homeostasis.

Methods and Results:
DNA damage assessed by γH2AX foci was observed in PAEC of EC-
Bmpr2
-/-
mice in room air, that was more extensive after reoxygenation (10% hypoxia for 3 weeks followed by recovery in room-air for 4 weeks). Deletion of the DNA damage sensor ataxia-telangiectasia mutated (ATM) in EC of mice (EC-
Atm
-/-
) also resulted in persistent DNA damage and PH. RNA sequencing of PAEC after reoxygenation in EC-
Bmpr2
-/-
and EC-
Atm
-/-
mice vs. controls showed downregulated EC differentiation and development genes enriched in biding motifs for
Foxf1, a
transcription factor associated with DNA repair and angiogenesis.
Foxf1
expression was reduced in PAEC with loss of BMPR2 or ATM. Loss of
Foxf1
decreased angiogenic genes
Cldn5
and
Vegfr2
, and DNA damage response genes
Atm
and
p53
, and impaired PAEC migration and tube formation.
Foxf1
overexpression increased these genes in PAEC. Immunohistochemistry showed decreased FOXF1 in PAEC of human pulmonary vascular lesions. Delivery of
Foxf1
to EC-
Bmpr2
-/-
mice with an AAV2-peptide targeting the PA endothelium attenuated DNA damage in PAEC, restored angiogenesis genes and completely reversed persistent PH returning right ventricular systolic pressure to normal levels.

Conclusions:
We link loss of BMPR2 and DNA damage sensing in PAEC to persistent DNA damage and PAH and show that both are mediated by reduced
FOXF1
. In EC-
Bmpr2
-/-
mice,
Foxf1
gene therapy attenuated DNA damage restored angiogenesis genes, and prevented persistent PH.
Abstract 9729: Pulling Out All the Stops (for a Diagnosis): A Case of Progressive Dyspnea
Authors: Ostrominski John W , Hollowell Monica L , Bhatt Deepak L , Scirica Benjamin M
Published: June 2023

A 63-year-old woman with hypertension, diabetes mellitus, severe obesity, obstructive sleep apnea, and history of GATA3+/ER+ breast cancer treated 14 years prior with neoadjuvant anthracycline-based chemotherapy and subsequent lumpectomy, chest radiotherapy, and letrozole presented to the emergency department with three weeks of progressive cough and exertional dyspnea. Physical examination revealed tachypnea, hypoxemia, a prominent P2, and jugular venous distension with a Kussmaul sign. Further investigation showed moderate hemolytic anemia, severe thrombocytopenia, and elevated natriuretic peptides. Electrocardiography revealed normal sinus rhythm, an S1Q3T3 pattern, and diffuse T wave inversions. Computed tomography angiography of the chest was notable for few small pulmonary nodules and diffuse vertebral osteosclerosis, consistent with osteoblastic metastases. Transthoracic echocardiography exhibited a moderately dilated RV with moderate systolic dysfunction, moderate TR, and an estimated RVSP of 79 mm Hg. Lung perfusion scintigraphy disclosed subtle subsegmental defects. Right heart catheterization (RHC) showed elevated right-sided filling pressures and severe precapillary pulmonary hypertension (RA 12 mm Hg, mPAP 51 mm Hg, PCWP 6 mm Hg, and PVR 775 dynes-sec/cm
5
). There was no discernable shunt. These findings, coupled with the patient’s history, rapidly progressive symptoms, and hematologic derangements, raised suspicion for pulmonary tumor thrombotic microangiopathy (PTTM). A pulmonary capillary wedge blood aspirate was sent for cytology. Her clinical status rapidly worsened despite inhaled pulmonary vasodilators, hemodynamic support, and systemic glucocorticoids, precluding candidacy for empirical chemotherapy. She was transitioned to comfort measures only and suffered a bradycardic PEA arrest on hospital day 8. Autopsy was declined. Cytological analysis of the wedge blood aspirate ultimately revealed clusters of neoplastic GATA3+ cells, consistent with PTTM associated with late recurrence of breast carcinoma. This case highlights the rare instance of PTTM diagnosis aided by wedge cytology, reinforcing the multidimensional role of RHC in this extremely uncommon and devastating clinical entity.
Abstract 9748: Association of Home-Based Cardiac Rehabilitation With Hospitalization Among a Diverse Cohort of Women With Cardiovascular Disease: A Propensity Score-Matched Study
Authors: Najem Michael , Duggan Mark , Gambatese Rebecca , Price Chileshe
Published: June 2023

Prior studies have demonstrated that home-based cardiac rehabilitation (HBCR) has similar outcomes compared to center-based cardiac rehabilitation (CBCR), however these studies have enrolled few women. The purpose of this study was to compare 12-month hospitalization rates among women who participated in HBCR and CBCR within an integrated health system in Southern California.

Using a retrospective cohort design, we evaluated women referred to HBCR and CBCR in Kaiser Permanente Southern California from April 1, 2018, to April 30, 2019. HBCR involved home-based exercise for 8 weeks complemented by a smartwatch exercise monitor and telephone support. CBCR involved center-based exercise sessions three times per week for a total of 36 sessions. Attendance of ≥1 session defined participation. After propensity score matching for age, race, Charlson score, referral reason, BMI, smoking history, atrial fibrillation, hypertension, prior MI, prior stroke, and history of hospitalization in the year prior to cardiac rehabilitation start, hospitalization rates at 12 months were compared among HBCR and CBCR groups.

Among 754 women who participated during the study period, 382 participated in HBCR and 372 participated in CBCR. Baseline demographics are presented in Table 1. After propensity score matching, women who participated in HBCR had similar hospitalization rates at 12 months, 17.0% (95% CI: [13.2%, 20.8%]) compared to women who participated in CBCR, 16.4% (95% CI: [12.1%, 20.8%]) (Figure 1).

In a propensity-matched, racially diverse population of women with cardiovascular disease, 12-month hospitalization rates were similar between women who participated in HBCR and CBCR.
Abstract 9749: Anthracicline-Induced Cardiotoxicity in Children. Pharmacogenetics and Clinical Study at a Tertiary Center
Authors: Moreno Toro Noelia , Marangoni Iglecias Luciana María , CARRERAS BLESA CARMEN , Rodriguez Vazquez del Rey Maria del Mar , Urrutia Maldonado Emilia , ortega Acosta maria jose , Pascual Gázquez Juan Francisco , Pelaez Pleguezuelos Irene , Perin Francesca
Published: June 2023

Introduction:
Children and adolescents treated with anthracyclines are at increased risk of developing cardiomyopathy. Although several guidelines are available, no consensus exists on an optimal strategy scheme for predict or avoid anthracycline-induced cardiotoxicity.

Methods:
Cardiotoxicity was defined as a reduction in left ventricle ejection fraction >10% from baseline and <53%, and/or global longitudinal strain drop of >15%.The incidence of cardiotoxicity, its relation with cumulative anthracycline doses, clinical significance and reversibility were retrospectively evaluated in a paediatric population (0-18 years) treated with anthracycline at a tertiary hospital (2010-2020). Analysis of 3 genetic polymorphisms related to cardiotoxicity (RARG (rs2229774), SLC28A3(rs7853758) and UGT1A6(rs17863783)) was performed.

Results:
A total of 84 patients (45 males) were included. The mean age at diagnosis was 10.7± 3.8 years with average cumulative anthracycline dose 195 mg/m2 (60-460mg/m2). Median follow-up was 5 years. Anthracycline-induced cardiotoxicity occurred in 12 (14,2%) of treated patients, 75% were asymptomatic. 5 patients experimented acute cardiotoxicity during treatment. 8 patients were treated with ACE-inhibitors and/or beta-blockers. 11 patients had full function recovery. Cumulative doxorubicin dose was a risk factor of cardiotoxicity, being affected 9/20 treated with >250 mg/m2; 3/51 treated with 100-250m2; while no patient out of 13 receiving <100 mg/m2 had an abnormal echocardiogram (P <0.01). A higher percentage of patients treated with mediastinum radiation and chemotherapy (3/7:42%) presented cardiotoxicity compared to those with chemotherapy only (9/77:9%) (p0.09). Younger age, female sex or the presence of genetic polymorphisms studied were not statistically significant risk factors.

Conclusions:
Dose-dependent anthracycline risk for developing cardiomyopathy was confirmed. However, previously identified risk factors including female sex, early age at diagnosis and genetic polymorphism were not replicated in this population, possibly due to the small sample size and the relatively short follow-up period. A tailored monitoring strategy based on cardiac risk stratification is needed.
Abstract 9778: The Biological Effects of a Novel Bispecific Designer Peptide (CRRL 094) in a Rat Model of Experimental Diabetes
Authors: Adel Fadi W , Zheng Ye , Pan Shuchong , AMEENUDDIN Syed , Chen Horng
Published: June 2023

Introduction:
The prevalence of diabetes mellitus (DM) is increasing, and it is associated with cardiorenal dysfunction. Natriuretic peptides (NPs) have cardiorenal protective actions and enhance insulin sensitivity. We designed a dual-action bispecific peptide (CRRL 094) that simultaneously activates the natriuretic peptide system and induces insulin secretion.

Methods:
To test the in vivo effects of the peptide, Wistar rats (male, 6-8-week-old) were made diabetic by intraperitoneal Streptozotocin (STZ) injection (65 mg/kg). One week after STZ injection, diabetes was confirmed (fasting blood glucose > 350 mg/dL). Rats were then divided into 2 groups: controls (Ctrl group, n=6) and treatment group (Tx group, n= 9). The peptide (1 pmol/kg/min) was infused in the Tx group for 150 min.

Results:
After 150 minutes of peptide infusion, plasma insulin (mean± standard deviation) increased more than 3.7x among the Tx group compared to the Ctrl group (0.294± 0.199 ng/mL vs 0.078± 0.021 ng/mL, p=0.01). Additionally, plasma glucose decreased among Tx group (405.3±96.4 mg/dL) compared to Ctrl group (545.6± 52.8 mg/dL, p=0.003). Furthermore, the rate of natriuresis increased significantly among the Tx group compared to controls (1.582±0.7 vs 0.639±0.21, p= 0.009), as did the rate of kaliuresis (3.1± 1.1 vs 2.0±0.6, p=0.045). Importantly, the glomerular filtration rate increased by 1.5x among the Tx group compared to the controls (1.6±0.5 vs 1.0±0.3, p= 0.03). There were no significant differences in mean arterial pressure or heart rate.

Conclusions:
The dual-action insulin-secreting natriuretic peptide (CRRL 094) was effective in increasing endogenous insulin secretion, enhancing natriuresis, and improving renal clearance. Further studies are warranted to assess its long-term safety and efficacy in diabetes.