bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 17461: Major Cardiovascular Events and Liver Disease in Patients With Truncating Variants in APOB and PSCK9
Authors: Knight Stacey , Le Viet T , Walton Nephi A , Christensen G B , Evans Jared M , May Heidi T , Anderson Jeffrey L , Nadauld Lincoln , Knowlton Kirk U
Published: December 2023

Introduction:
Truncated variants in the genes
ApoB
and
PSCK9
have been shown to be associated with low levels of low-density lipoprotein cholesterol (LDL-C), however, there is concern about the increased risk of liver disease. Using Intermountain Health’s HerediGene Population Study, a population-based genetic study, we sought to understand the impact of these variants on major adverse cardiovascular events (MACE) and liver disease.

Methods:
Of the 32,159 sequenced patients (pts), 58 (0.18%) had a truncating variant in
ApoB
(n=49) and
PCSK9
(n=10). Among those with a truncating variant, we compared the demographics, LDL-C levels, statin use, and disease by MACE (including, myocardial infarction [MI], heart failure (HF) hospitalization, stroke, peripheral artery disease, and carotid artery disease).

Results:
MACE occurred in 32% of pts, with HF hospitalization followed by MI being the most frequent. The rates of MACE were similar for pts with
ApoB
(n=15, 30.6%) and
PCSK9 (n=
4, 40%). Differences in demographics and clinical characteristics stratified by MACE are shown in the Table. LDL-C levels were low in both groups, with approximately half having an LDL-C <70 mg/dL. Hypertension was more common in the MACE group (95% vs 50%). Both groups had high rates of liver disease (47%) compared to the general patient population (9%). Renal failure was also common among these pts (36%). Only 2 of the deaths (both in the MACE group) were cardiovascular-related, 1 due to stroke and 1 due to heart failure.

Conclusion:
Low LDL-C was associated with truncated variants in the
ApoB
and
PSCK9
genes. However, these patients still had a high rate of MACE, which was driven mainly by hypertensive diseases. Frequency of liver disease and renal failure was high, which may also be attributed to hypertension. While this is a small sample, these findings suggest that continued screening for cardiovascular disease is needed despite low LDL-C, with liver disease screening also needing to be performed.
Abstract 17486: Non-Proportional Hazards in Randomized Cardiology Clinical Trials: A Standardized Universal Secondary Analysis (SUSAN) to Enhance Clinically Meaningful Appraisal of Results
Authors: Roumeliotis Anastasios , Tijssen Jan G , Dangas George
Published: December 2023

Introduction:
In patients with CAD, more invasive interventions are expected to have more early complications in anticipation of improved longer-term outcomes. This often leads to violation of the proportional hazard (PH) hypothesis, thereby complicating interpretation of results.

Hypothesis:
Analyzing the early and late post-procedural periods separately may provide important additional information for clinicians beyond the cumulative outcome.

Methods:
We identified 36 RCTs comparing more versus less invasive strategies for the management of CAD. Of those, 16 exhibited crossover of the Kaplan Meier curves, indicating violation of PH. Hereafter, we focus on 4 landmark trials exhibiting such findings: STICH, EXCEL, FREEDOM, and ISCHEMIA. Complete results in all trials will be presented.

Results:
Initial evaluation of outcomes violating PH includes assessment using algorithms testing proportionality. Thereafter, focus should be shifted not to the time of crossing of curves, but to identifying the time of trend switch: this signifies transition from the earlier to the later disease states (acute/peri procedure or longer term/chronic phase) and may be accomplished by calculation of instantaneous hazards. Following this, the two clinically relevant periods should be studied individually to quantify the impact of different approaches in each of the periods (Figure). As a final step, the cumulative effect of the intervention on hard endpoints should be calculated using statistical designs not assuming proportionality, such as Restricted Free Survival Time or the Com-Nougue.

Conclusions:
In addition to the cumulative assessment of the primary endpoint, SUSAN allows analysis of the two post-procedural periods separately, as identified by the point of trend switch. This would be particularly informative for clinicians and patients in reviewing early risks and late benefits; adhering to a standardized method may allow a universal presentation of RCT results.
Abstract 17495: Protein Kinase A Activity in Heart Failure Spectrums
Authors: Dasari Tarun W , Myers Jennifer , Stavrakis Stavros , Cunningham Madeleine W
Published: December 2023

Introduction:
Protein Kinase A (PKA) signaling is activated by β-adrenergic receptor (BAR) stimulation and regulates myocardial contraction and cellular functions. Chronic PKA overactivation can lead to apoptosis, structural dysfunction and arrhythmias. Heart failure (HF) is associated with increased BAR stimulation and downstream detrimental cellular effects likely mediated by increased PKA activation, but it remains unclear whether PKA is uniformly increased across HF spectrums. We aimed to determine the extent of PKA activity in HF phenotypes.

Methods:
Serum from HF patients (age 18-89, 66% male) (acute systolic HF, n=19, HF with reduced ejection fraction HFrEF (n=58) and HF with preserved ejection fraction-HFpEF (n=10) were collected. PKA assay: H9c2 rat heart cells (ATCC) were plated overnight and serum samples (1:100 dilution) were incubated with cells for 1 hour. Specific activity of the enzyme in pmol/min/ng was calculated (% above the basal PKA rate). For comparison, healthy controls (n=35, age 18-69, 59% male) were tested. In 3 HFrEF subjects, serum PKA signaling was inhibited by anti-IgG beads, specific antigens or Propranolol. Mann Whitney U test was performed to determine differences between groups.

Results:
Median PKA activation was 76% (acute HF), 49% in HFrEF, 39% in HFpEF and 9% in healthy controls. Compared to controls, PKA activity was significantly higher across all HF phenotypes (p<0.05). No statistical difference was noted between HF phenotypes although acute HF sera demonstrated numerically higher PKA activation in the heart cells. PKA activity was attenuated with anti-IgG beads or Propranolol in HFrEF, which suggests circulating IgG autoantibodies lead to induction of PKA signaling via BAR pathway in HF.

Conclusion:
PKA activity is increased across HF spectrums compared with healthy controls. Acute systolic HF appears to be associated with highest PKA activation. Further studies are underway to corroborate these findings.
Abstract 17496: Exploring the Benefits: Role of Repeat Transesophageal Echocardiography (TEE) in Patients Anticoagulated for Four Weeks
Authors: Khatun Nazima , Nnadi Ekendilichukwu , nigussie bisrat , Graham-Hill Suzette
Published: December 2023

Background:
A left atrial appendage (LAA) thrombus is a well-known complication of atrial fibrillation (AF). Vitamin K antagonists (VKAs) have been well studied been considered the gold standard for thromboembolic prophylaxis. We present a case of LAA thrombus despite compliance with VKAs.

Clinical presentation:
A 70-year-old female with atrial fibrillation and diabetes presented with left-sided weakness and left facial droop, CT head showed right middle cerebral artery infarct. Vitals were unremarkable. Electrocardiogram showed AF with a rapid ventricular response. She was on warfarin with the most recent international normalized ratio level of 2.3. Transthoracic echocardiography revealed an ejection fraction of 55%, severe left ventricular hypertrophy, and severely dilated left atrium (LA) with LA diameter of 5.3 cm (>= 4.7 cm in women indicates severe dilatation). Transesophageal echocardiography (TEE) with bubble study demonstrated a large thrombus in the LAA with evidence of patent foramen ovale. The pulse wave Doppler (PWD) of the LAA on TEE also showed an LAA velocity of <20 cm/sec, which indicated that there was the highest probability that the thrombus was forming within LAA. Hypercoagulability work-up for thrombosis while on Coumadin such as anti-B2 glycoprotein, anticardiolipin, and factor V Leiden mutation were negative. The patient was started on enoxaparin with appropriate follow-up upon discharge.

Discussion:
The prevalence of LAA thrombus in patients with AF receiving a minimum of 3 weeks of anticoagulation, was approximately 3%. The presence of a LAA thrombus is a known contraindication to cardioversion and catheter ablation in patients with AF as it can result in cardioembolic stroke. However, current guidelines for cardioversion do not recommend pre-procedural TEE in patients undergoing cardioversion for AF if they have been on therapeutic oral anticoagulation for at least 3 weeks while TEE use remains variable before catheter ablation.
Abstract 17504: Revisiting the Etiology of a Non-Ischemic Cardiomyopathy
Authors: Steverson Alexandra B , Kawana Masataka
Published: December 2023

Introduction:
In the era of REVIVED-BCIS2 and ISCHEMIA clinical trials, the role of routine invasive coronary angiography for treatment of coronary artery disease (CAD) in the setting of left ventricular dysfunction has come into question. While the majority of heart failure (HF) patients undergo some form of non-invasive ischemic evaluation, there are a wide range of opinions on which testing modality is the most appropriate.

Case:
This is a 53 year-old man with a history of HTN, HLD, and presumed non-ischemic cardiomyopathy and LVEF of 15-20%, first diagnosed in 2009. He had a family hx of heart disease in several distant relatives, thus the etiology was presumed familial. In 2022, he had NYHA class II symptoms and a routine echo showed a LVEF of 25% with anteroseptal hypokinesis. Given these findings, a coronary CTA was obtained. This demonstrated infarct in the LAD territory and a proximal left main to mid-LAD aneurysm measuring up to 7 mm with a partially calcified shell and peripheral thrombus, consistent with prior Kawasaki’s disease (KD). He was initiated on a DOAC to prevent further embolic events and aspirin. He is now undergoing serial monitoring of the aneurysm size, thrombus burden, and functional testing to monitor for ischemia.

Discussion:
Non-invasive anatomic testing to evaluate for CAD in HF patients can provide useful information over a functional assessment. KD is a rare disease with an estimated incidence rate of ≈25 per 100,000 children less than 5 years of age. KD can lead to coronary artery aneurysms, which often contain thrombi, and subacute/chronic myocarditis. The affected arteries can become stenotic over time or even occlude, leading to ischemic injury later in life. Early recognition of this rare disease is important to initiate appropriate treatment and prevent thromboembolic complications.

Conclusion:
KD is a rare cause of adult cardiomyopathy. Anatomic testing was essential to appropriately diagnose and treat this patient’s cardiomyopathy.
Abstract 17514: Changing Default Prescription Length to Reduce Barriers to Statin Adherence
Authors: Mehta Mili , Fanaroff Alexander C , Rhodes Corrine M , Xiong Aria , Snider Christopher K , Fagen E. Madeline , Mehrabyan Nune , Peifer MaryAnne K , Volpp Kevin , Delgado M. Kit
Published: December 2023

Introduction:
Statins substantially reduce cardiovascular risk, yet adherence is suboptimal. 90-day prescription fills are associated with better adherence than 30-day fills, though many prescriptions are not written for 90 days. We evaluated the effect of changing default prescription length to 90 days within the electronic health record (EHR) on the proportion of statin prescriptions written for 90 days.

Methods:
At a single academic health system, we changed the default duration for statin prescriptions written using the primary care preference list within the EHR to 90 pills with 3 refills, while still allowing providers to make a manual change. We compared the proportion of prescriptions written for 90 days over the 4 months before the change (pre-intervention) and 4 months after the change (post-intervention) using a chi-square test, along with need to change prescription dose or drug during the 90-day period after the prescription was written, a potential unintended consequence.

Results:
Among statin prescriptions written using the primary care prescription preference list, the rate of prescriptions written for 90 days increased from 70.6% pre-intervention to 90.1% post-intervention (p<0.001). Pre-intervention, patients with Medicaid insurance, median ZIP code household income < $50,000, and Black race were significantly less likely to be prescribed a 90-day statin supply (p <0.05). The intervention increased the proportion of 90-day prescriptions more in these groups (interaction p < 0.01), and they were no longer less likely to be prescribed a 90-day supply in the post-intervention period. Post-intervention, there was no change in the proportion of patients that needed a change in prescription during the active prescription time period (p=0.15).

Conclusion:
Changing default options significantly increased the proportion of statin prescriptions written for 90 days and closed baseline equity gaps without restricting patient or physician choice.
Abstract 17520: Dynamic Intrapulmonary Shunting in the Setting of Amphetamine Use
Authors: Samaan Sara , Ardhanari Sivakumar
Published: December 2023

Description of Case:
A 35-year-old female non-smoker with ADHD on amphetamine for the past 3 months and family history of hereditary hemorrhagic telangiectasia (HHT) presented with significant exertional dyspnea for 1 week. She was hypoxic to 82% while walking, with normal oxygen saturation at rest. Transthoracic echocardiogram with agitated saline revealed extracardiac right-to-left shunting with exercise and Valsalva. This was confirmed by dobutamine stress echocardiogram with agitated saline (Figure 1A). Transesophageal echocardiogram with agitated saline (Figure 1B) revealed no shunt through the foramen ovale, but it demonstrated bubbles entering from the left upper pulmonary vein, suggestive of an extracardiac shunt from a pulmonary arteriovenous malformation (AVM). Right heart catheterization and pulmonary angiogram revealed normal pressures, and no pulmonary abnormalities with normal pulmonary venous return. Supine right heart catheterization with exercise revealed normal pressures, although the initial pulmonary artery (PA) saturation was 28%; repeat PA saturation one minute later was 48%. Arterial saturation was 95%. Pulmonary function testing, ventilation perfusion scan, high-resolution CT chest, and coronary CT angiogram were unremarkable. The patient was instructed to avoid all stimulants, and to take a non-hormonal contraceptive. At her 3-month follow-up, she reported significant improvement in her symptoms. She underwent a 6-minute walk test, and her lowest oxygen saturation was 88%.

Discussion:
This patient presented with exertional hypoxia, normal saturations at rest, evidence of an extracardiac shunt only with exertion and absence of clear sources of the shunt on imaging. With her family history of HHT, this is suggestive of a small pulmonary AVM that opened by elevated PA pressures, likely triggered by amphetamine use, and its discontinuation led to symptom resolution.
Abstract 17536: Real World Analysis from the "Fast STEMI" Registry on Adherence and Discontinuation of Statin Therapy Within 6 Months After ST-Elevation Myocardial Infarction on First Year Follow-Up: Prognostic Impact and Predictors of Adherence
Authors: morena arianna , Giacobbe Federico , Annone Umberto , Ravetti Emanuele , di vita umberto , Giannino Giuseppe , Troncone Mattia , Carmagnola Ludovica , Dusi Veronica , Nebiolo Marco , De Filippo Ovidio , Bruno Francesco , D'Ascenzo Fabrizio , Giammaria Massimo , De Ferrari Gaetano Maria
Published: December 2023

Background:
The impact of statin therapy on cardiovascular outcomes after ST-elevation acute myocardial infarction (STEMI) in real-world patients is understudied.

Objectives:
to identify predictors of low adherence and discontinuation to statin therapy within 6 months after STEMI and to estimate their impact on cardiovascular outcomes at one year follow-up.

Methods:
We evaluated real-world adherence to statin therapy by comparing the number of bought tablets to the expected ones at 1 year follow-up through pharmacy registries. A total of 6043 STEMI patients admitted from 2012 to 2017 were enrolled in the FAST STEMI registry and followed up for 4,7±1,6 years; 299 patients with intraprocedural and intrahospital deaths were excluded. The main outcomes evaluated were all-cause death, cardiovascular death, myocardial infarction, major and minor bleeding events, and ischemic stroke. The compliance cut-off chosen was 80% as mainly reported in literature.

Results:
From a total of 5744 patients, 418 (7,2%) patients interrupted statin therapy within 6 months after STEMI. After univariate and multivariate analysis age over 75 years old, known ischemic cardiopathy and female gender resulted as predictors of therapy discontinuation. Statin discontinuation within 6 months showed an increase of both cardiovascular (5% vs 1.7%; HR 2.23; 95%CI 1.37-3.65; p=0,001) and all-cause mortality (14.8% vs 5.1%, HR 2.32; 95%CI 1.73-3.11; p<0,001) at 1 year follow-up. Regarding cardiovascular outcomes, statin optimal adherence (>80%) reduced ischemic stroke incidence (1% vs 2.5%, p=0.001) and both cardiovascular and all-cause death (0.1% vs 4.6%; 0.3% vs 13.4%; p<0.001) at 1 year follow-up. Age over 75 years old, chronic renal failure, previous atrial fibrillation, vasculopathy, known ischemic cardiopathy were found to be predictors of low statin adherence.

Conclusions:
In our real-world registry low statin adherence and discontinuation therapy within 6 months after STEMI were independently associated to an increase of cardiovascular and all-cause mortality at 1 year follow-up. Low statin adherence led to higher rates of ischemic stroke. This analysis confirmed the predictive factors of adherence and discontinuation therapy already described in literature.
Abstract 17540: Functional Mitral Regurgitation is Associated With Decreased Papillary Muscle Viability Patients With Non-Ischemic Dilated Cardiomyopathy
Authors: Frljak Sabina , Zorz Neza , Poglajen Gregor , Vrtovec Bojan
Published: December 2023

Background:
The underlying mechanisms of functional mitral regurgitation (FMR) in non-ischemic cardiomyopathy (NICM) are incompletely understood.

Aims:
We investigated the correlation between papillary muscle viability and FMR in NICM.

Methods:
We enrolled 66 patients with NICM (LVEF<40%, NHYA III) undergoing CD34
+
cell transplantation. At baseline, patients underwent electroanatomical mapping; papillary muscle viability was quantified by local unipolar voltage (UV) measurement, and decreased viability was defined as UV<8.3 mV. All patients received granulocyte-colony stimulating factor; CD34
+
cells were collected by apheresis and delivered by transendocardial injections. Echocardiography was performed at baseline and 6 months after cell therapy; severity of FMR was graded by multi-parametric approach. FMR improvement was defined as a reduction in FMR by ≥1 grade when compared to baseline.

Results:
At baseline, papillary muscle viability was decreased in 24 (36%) and preserved in 42 (64%) of patients. Moderate to severe (2-3+) FMR was more common in patients with decreased papillary muscle viability (6/24; 25%) than in patients with preserved viability (2/42; 5%, P=0.015). Transendocardial cell injections were performed in the papillary muscle area in 26 patients (Group A) and in other areas of the left ventricle in 40 patients (Group B). The groups did not differ in age (56±11 years in Group A vs. 54±10 years in Group B, P=0.32), sex (male: 96% vs. 85%, P=0.21), creatinine (0.98±0.27 mg/dL vs. 0.96±0.28 mg/dL, P=0.92), bilirubin (0.89±0.37 mg/dL vs. 0.92±0.35 mg/dL, P=0.45), LVEF (34±9% vs. 31±7%, P=0.12), NT-proBNP levels (1196±994 pg/mL vs. 1077±1176 pg/mL, P=0.68), the degree of FMR (1.28±0.78 vs. 1.02±0.38, P=0.20), or papillary muscle viability (9.9±3.0 mV vs. 10.3±3.2 mV, P=0.62). At 6 months after cell injection, FMR improved in 77% of patients in Group A vs. 13% in Group B (P=0.001). On multivariate analysis, cell injection in the papillary muscle area was an independent correlate of FMR improvement (P=0.01).

Conclusions:
FMR in patients with NICM is associated with decreased papillary muscle viability. Transendocardial injection of CD34
+
cells in the papillary muscle area may improve FMR in this patient population.
Abstract 17571: Lessons From Launching a Digital Health Trial for Hybrid Cardiac Rehabilitation
Authors: Kim Chang H , Nimbalkar Mansi , Isakadze Nino , Gao Yumin , MacFarlane Zane , Ding Jie , Broderick Ashley , Bush Alexandra , Gallagher Jeanmarie , Wiley Brittany , Lobien Jackie , Reddy Tara , Aguado Carlos , Benjamin Preeti , Neigh Brittany , Stewart Kerry J , Mathews Lena M , Spaulding Erin , Martin Seth S , Marvel Francoise A
Published: December 2023

BACKGROUND:
Despite the well-established benefits of cardiac rehabilitation (CR) for secondary prevention of cardiovascular disease, participation remains low due to limited supply and access barriers. We built a hybrid CR program that combines in-person and home-based CR (with smartphone app (Corrie Health), smartwatch, Bluetooth blood pressure monitor, and health coaching delivered over 12 weeks). We assessed this novel CR program in a pilot study at Johns Hopkins Hospital and applied the lessons learned to launch a randomized controlled trial (mTECH REHAB; NCT05238103) of hybrid versus traditional CR.

METHODS:
We examined pilot data from Nov 2022 to Feb 2023 for electronic health record (EHR) screening, bedside enrollment, technology onboarding, access to CR, and weekly health coaching. We identified barriers in the enrollment process which we then used to guide trial design and team organization.

RESULTS:
EHR screening yielded 1,270 candidates, among which 209 (16.5%) were eligible following chart review. Our team approached 106 (50.7%) at bedside and 20 (9.6%) were enrolled into the pilot study. Ten (50.0%) were lost to follow up, with reasons of: loss of interest (3), post-procedural complication (3), frailty requiring acute CR (1), no insurance coverage (1), follow up in external CR (1), and technology challenges (1). These findings informed trial design as follows: 1) pre-specified filters for cardiovascular procedures/surgeries were added to EHR screening; 2) remote enrollment pathway was added; 3) a 2-week run-in period was added to verify insurance and continued interest following hospital discharge; and 4) standardized workflows and specialized teams were developed for patient recruitment, technology onboarding, and health coaching. The mTECH REHAB trial was launched in Apr 2023. In the first 9 weeks, 851 patients were screened, 157 (18.4%) were eligible, 148 (94.2%) were able to be reached at bedside or via telephone, 41 (27.7%; 16 bedside, 25 remote) were enrolled, and 5 (12.2%) were lost to early follow up because of: loss of interest (3), post-procedural complication (1), and patient relocation (1).

CONCLUSIONS:
A pilot study can inform and improve the enrollment process in a multi-component digital health trial.
Abstract 17577: Cardiomyopathy With Positive ATTR Mutation but Negative Tc-PYP Scan: A Conundrum
Authors: Iyer Charoo , Abbas Syed Faiz F , Niu Chengu , Lee Elizabeth
Published: December 2023

Background:
Cardiac amyloidosis (CA) is a Hypertrophic Cardiomyopathy (HCM) mimic. Technetium labeled pyrophosphate (Tc-PYP) scan provides a rapid & non-invasive means for identifying ATTR-type CA with 99% sensitivity and specificity. We present 2 patients who were referred to HCM clinic but were found to have genetic testing positive for hTTR. In both cases, Tc-PYP scan was negative.

Case Presentation:
Outlined in Figure 1.

Discussion:
Both cases present a diagnostic and management dilemma. Neither of these two patients can be strictly considered asymptomatic carriers of the ATTR gene as both had phenotypic expression in the form of cardiomyopathy & massive LVH on imaging. Yet, in both Tc-PYP scan was negative. Neither had the ATTR mutations (Phe64Leu and Val30Met) that have reported association with negative Tc-PYP scan. Another possibility is early CA, which maybe rarely associated with negative Tc-PYP scan. Patient 1 refused endomyocardial biopsy, so early CA remains on the differential for her. Patient 2 had a negative endomyocardial biopsy. Her case is unique due to history of liver transplant 20 years prior to presentation making phenotypic CA less likely, but not impossible as there have been prior reports of cardiac disease progressing even after liver transplantation in familial ATTR. She also had tacrolimus exposure, which is known to cause LVH in rare cases. Both patients had hypertension, which could have also contributed to LVH. This case series serves to highlight the importance of maintaining a broad differential diagnosis in patients undergoing evaluation for HFpEF and severe LVH, particularly in cases of positive genetic testing but negative PYP scan for CA. From a management standpoint, it is unclear if early initiation of tafamidis might have a role in preventing cardiomyopathy progression in such patients with diagnostic uncertainty & ongoing concern for early CA.
Abstract 17578: Improving Access to Care With a Structural Heart Disease Program in a Metropolitan Public Healthcare System
Authors: Harari Rafael , Bernard Samuel , Shah Binita , Nayar Ambika , Small Adam , Goldberg Randal , Halpern Dan , DiVita Michael , Sutin Kenneth , rostanski sara , Lillemoe Kaitlyn , Cruz Jennifer , Elbaum Lindsay , neuburger peter , Hussain Syed , Padilla Lopez Mireia , Wan Kah-Loon , Kroczynski Nicolette , Jain Sudheer , Alviar Carlos L , Bangalore Sripal , Keller Norma
Published: December 2023

Background:
Public hospitals face challenges in providing access to structural heart interventions due to limited resources. Our aim is to describe the implementation and outcomes of a comprehensive, multi-disciplinary Structural Heart Disease Program (SHDP) in the largest public healthcare system in the United States, as a strategy to mitigate healthcare disparities and improve access to care.

Methods:
The SHDP at Bellevue Hospital serves as the referral center for 11 public hospitals in New York. It launched in 2022 and added a hybrid OR in March 2023. We collected clinical, demographic, and socioeconomic data for patients undergoing structural heart interventions.

Results:
A total of 56 patients were included from January 2022 to June 2023. The median age was 60 years (22-93 years), 59% were women, 41% were Black, 38% Hispanic, 11% White and 9% Asian. Most patients were immigrants (71%), 28.5% were uninsured, 37.5% were undocumented and 41% required an English interpreter. Only 21% of patients completed high school and 9% completed college. The most common procedure was PFO closure (30%) followed by M-TEER and BAV (Figure 1). For TAVRs and M-TEERs combined, the 30-day re-admission rate was 7.1% (n=1) and 30-day mortality was 0%, with no differences by ethnic group. Length of stay varied by procedure and there were low rates of procedural complications (Table 1).

Conclusions:
Our multidisciplinary SHDP program demonstrates feasibility to provide care to underserved populations in a public healthcare system with excellent outcomes. Further study of strategies aimed at improving access to structural heart interventions is warranted.
Abstract 17594: The Impact of Socioeconomic Status on Anthracycline Cardiotoxicity in a Diverse Population
Authors: Song Justin J , Hanif Waqas , Clark Rachel , Haroun Magued , Fernandez Hazim Carol , McNaughton Caroline , Slipczuk Leandro , Garcia Mario J , Pu Min , Gongora Carlos , Neilan Tomas G , Makower Della , Sica Roberto Alejandro , Chambers Earle , Rodriguez Carlos J , Zhang Lili
Published: December 2023

Introduction:
There are sparse data on the impact of socioeconomic status (SES) on the incidence of anthracycline cardiotoxicity.

Aims:
To examine the association of neighborhood-level SES factors with anthracycline cardiotoxicity.

Methods:
We included consecutive adult patients who underwent anthracycline-based chemotherapy from 2016 to 2019 for any type of cancer in the Montefiore Health System. The endpoint was the development of cardiotoxicity (defined as clinical heart failure or drop in left ventricular ejection fraction [LVEF]≥10% to LVEF<53%). We analyzed neighborhood-level SES measures (median household income [MHI], high school graduate rate, employment rate), and composite indices of neighborhood-level social disadvantage (the Social Vulnerability Index [SVI] and Area Deprivation Index [ADI]), with higher scores indicating worse neighborhood-level SES.

Results:
A total of 925 patients (22% Non-Hispanic White (NHW), 25% Non-Hispanic Black (NHB), 31% Hispanic, and 2% Non-Hispanic Asian) were included. During a median follow-up of 21 months, 116 patients (13%) developed cardiotoxicity. Patients who developed cardiotoxicity had significantly lower MHI, lower high school graduation rates, lower employment rates, higher SVI and ADI compared with patients who did not develop cardiotoxicity (all p<0.01). In multivariable adjusted Cox Proportional-Hazards models, MHI (1
st
quartile vs 4
th
quartile HR 2.1, p=0.024), SVI (HR 3.66, p=0.014) and ADI (HR 1.01, p=0.018) were significantly associated with a higher risk of cardiotoxicity development after adjusting for age, sex, cardiovascular risk factors, baseline LVEF, and anthracycline dose. ADI remained significantly associated with cardiotoxicity after adjustment for race/ethnicity (HR 1.01, p=0.046).

Conclusions:
In a large, socioeconomically diverse cohort of cancer survivors treated with anthracycline-based chemotherapy, SES indices were associated with the development of cardiotoxicity. ADI may be a better predictor of cardiotoxicity independent of race/ethnicity.
Abstract 17599: Sotatercept for the Treatment of Pulmonary Arterial Hypertension: A Systematic Review and Single-Arm Meta-Analysis
Authors: Felix Nicole , Teixeira Larissa , Campedelli Luiz , Nogueira Alleh , Godoi Amanda , Deberaldini Marinho Alice , Deberaldini Marinho Beatriz , Perim C N Victor , Costa Thomaz A , Risbano Michael G
Published: December 2023

Introduction:
Pulmonary arterial hypertension (PAH) is associated with progressive clinical worsening and a 50% 5-year survival rate with current PAH therapies. Sotatercept is a first-in-class fusion protein with promising results in preclinical trials, but clinical evidence on its role in treating PAH remains limited.

Hypothesis:
Sotatercept may provide clinical benefits for patients with symptomatic PAH.

Aims:
To assess the efficacy of sotatercept in addition to background PAH therapy in this population.

Methods:
We searched PubMed, Embase, Cochrane and Clinicaltrials.gov in April 2023 for clinical trials assessing efficacy outcomes of sotatercept in patients with PAH. Using a random-effects model, we performed a single-arm meta-analysis of proportions for binary outcomes and applied generic inverse variance weighting formulas to pool arithmetic means and least squares means for continuous outcomes. Statistical analyses were performed using Review Manager 5.4.1 and R software 4.2.2.

Results:
We included three clinical trials comprising 254 patients with WHO functional class II or III PAH. At 24 weeks, only 2% of patients on sotatercept experienced symptoms of clinical worsening (95% CI 1 to 5; Fig. 1A). Sotatercept was also associated with a reduction in pulmonary vascular resistance (mean change from baseline -199.92 dyn·sec·cm
-5
; 95% CI -256.83 to -143.0; Fig. 1B), while improving 6-minute walk distance (mean change from baseline 45.86 m; 95% CI 28.54 to 63.18; Fig. 1C).

Conclusions:
These findings suggest that sotatercept may improve exercise capacity while decelerating clinical worsening and attenuating pulmonary vascular resistance in patients with mild to moderate PAH.
Abstract 176: The Pathological Role of Aldose Reductase in Isolated Cardiomyocytes Undergoing Hypoxia / Reoxygenation After Prior Exposure to High Glucose Concentrations
Authors: Walter Miriam J , Shiota Masakazu , Li Zhu , Barajas Matthew B , Oyama Takuro , Riess Matthias L
Published: December 2023

Hyperglycemia increases the vulnerability of the cardiovascular system to ischemia/reperfusion (IR) injury. There are currently no effective therapeutic strategies.

We hypothesized that hyperglycemia would increase glucose flux through the polyol pathway. Aldose reductase (AR) catalyzes the first step of this pathway by converting glucose to sorbitol. This reaction generates more oxidative stress due to the depletion of NADPH and osmotic stress caused by sorbitol accumulation, making the heart more susceptible to IR injury. This study aimed to better understand the injury mechanism in cardiomyocytes after high glucose exposure and IR injury.

Confluent cardiomyocytes were exposed for 24 hours to 25, 50, or 100 mM glucose or 25 mM glucose with 25 or 75 mM sucrose concentrations added. The non-metabolizable sugar sucrose was used as an osmolarity control. Epalrestat, an AR inhibitor, was added at 0, 1, or 10 μM per well (n = 18 per group) during glucose or sucrose exposure. Cells were then subjected to 24 hours of hypoxic conditions (glucose-, sucrose- and serum-free media; 0.01% O
2
, 37 °C; hypoxic chamber) or normoxic conditions (complete media; 21% O
2
, 37 °C), followed by a 2-hour reoxygenation period in normoxic conditions. Cell injury was quantified by measurement of lactate dehydrogenase (LDH) release.

Data were normalized to 25 mM glucose after control/normoxic conditions without AR inhibitor. A three-way ANOVA was conducted to compare groups, followed by the Holm-Šidák test.

Increasing glucose concentrations lead to increased cell damage after hypoxia/reoxygenation. Adding the AR inhibitor during the glucose exposure period reduced LDH release after hypoxia/reoxygenation in a dose-dependent manner. The addition of sucrose did not increase cell injury. The AR inhibitor did not affect cells exposed to sucrose. The polyol pathway may play a dominant role in increased cell injury by hyperglycemia after hypoxia/reoxygenation.
Abstract 17623: Estrogen-Mediated Small GTP-Binding Protein GDP Dissociation Stimulator Induction Contributes to Sex Differences in Resilience to Ferroptosis in Takotsubo Syndrome
Authors: Wang Ti , Xiong Ting , Liu Xuesong , Yang Yuxue , Chen Xiwei , Zhou Beibei , Lin Zhiyong , Wang Daxin
Published: December 2023

Introduction:
Declining estrogen (E2) has been associated with disproportionate susceptibility to takotsubo syndrome (TTS) in postmenopausal women. Small GTP-binding protein GDP dissociation stimulator (SmgGDS), as a key modulator of cardiovascular disease, plays protective roles in reducing oxidative stress and exerts pleiotropic effects of statins. Whether SmgGDS levels are influenced by E2 status and the effect of SmgGDS on sex differences in TTS are poorly understood.

Methods:
Clinical data were reviewed from TTS inpatients. Echocardiography, immunofluorescence, and immunohistochemistry were performed together with expression analysis to uncover phenotypic and mechanism changes in sex differences in TTS-like wild-type (
WT
) and

SmgGDS
+/-

mice. HL-1 cardiomyocytes were used to further examine molecular mechanisms.

Results:
In 14 TTS inpatients, TTS had a higher incidence in postmenopausal women as compared to premenopausal women and men. In murine TTS, female
WT
mice exhibited higher cardiac SmgGDS levels than male
WT
mice. Ovariectomy reduced SmgGDS expression in female
WT
mice, whereas E2 replacement reversed this effect. The physiological importance of this sex-specific E2-mediated SmgGDS response is underscored by the disparity in cardiac adaptation to isoproterenol (ISO) stimulation between both sexes of
WT
mice. E2-mediated SmgGDS induction conferred female cardioprotection against ferritinophagy-mediated ferroptosis. No such cardioprotection was observed in male
WT
mice and ovariectomized (OVX) female mice. A causal role for SmgGDS in this sex-specific cardioprotective adaptation was indicated, inasmuch as SmgGDS deficiency abolished E2-modulated cardioprotection against ferritinophagy and aggravated TTS progression in both sexes. Consistently, knockdown of SmgGDS in HL-1 cardiomyocytes exacerbated ferritinophagy and abrogated the protective role of E2 against ferritinophagy. Mechanistically, our findings revealed that SmgGDS deficiency abolished E2-conferred protection against ferritinophagy through activating AMPK/mTOR pathway.

Conclusions:
These results demonstrate SmgGDS is a central mediator of E2-conferred female cardioprotection against ferritinophagy-mediated ferroptosis in TTS.
Abstract 17631: Diabetic Retinopathy and Risk of Heart Failure Subtypes: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Echouffo Justin B , Ndumele Chiadi E , Zhang Sui , Sharrett A R , Matsushita Kuni , Coresh Josef , Shah Amil M , Selvin Elizabeth
Published: December 2023

Introduction:
Although diabetic retinopathy is associated with higher risk of incident heart failure (HF), its associations with HF subtypes (HF with preserved ejection fraction [HFpEF] and HF with reduced ejection fraction [HFrEF]) largely remain unknown.

Hypothesis:
Diabetic retinopathy, a microvascular complication of hyperglycemic states, is more strongly associated with HFpEF than with HFrEF.

Methods:
We included 5038 ARIC participants who underwent fundus photography at Visit 3 (1993-1995), had diabetes or prediabetes, and were free of HF (mean age 60 years, 48% women, 27% Black adults). Retinopathy was graded according to the Early Treatment of Diabetic Retinopathy Study (ETDRS) grading scale, with a severity score ≥14 defining the presence of any retinopathy. We used data on incident HF hospitalization. Information on HF subtypes was only available from 2005 onwards. We used Cox regression to estimate the associations of retinopathy with incident overall HF. For HF subtypes, to account for the competing risks of HFpEF and HFrEF, we used competing risks regression analysis by the proportional sub-hazards Fine and Gray method.

Results:
Over a median 21.2 years of follow-up, there were 1358 HF events (461 prior to 2005 and 897 post-2005 [including 418 HFpEF and 383 HFrEF]). The presence of diabetic retinopathy conferred higher risk of overall HF (hazard ratio [HR]: 1.84, 95% confidence interval [CI]: 1.55, 2.20). Among participants with information on HF subtypes post-2005 (n= 4120), diabetic retinopathy significantly increased the risk of HFpEF (HR 1.86, 95% CI: 1.28, 2.71), but not of HFrEF (sub-HR: 0.73, 95% CI: 0.45, 1.20). An increasing severity of diabetes retinopathy was associated with increasing risks of overall HF and HFpEF.

Conclusions:
The presence of diabetic retinopathy signifies an excess risk of HF, primarily HFpEF. Our findings support a strong contribution of microvascular disease to the development of HFpEF.
Abstract 17634: CCN2 Deficiency in Vascular Smooth Muscle Cells Drives the Progression of Atherosclerosis
Authors: Xu Qian , Holden Claire , Ferreira Neto Hildebrando , Lin Zhiyong
Published: December 2023

Introduction:
Atherogenesis involves a complex interaction between immune cells and lipids, processes greatly influenced by the vascular smooth muscle cells (VSMCs) phenotype. Cellular communication network factor 2 (CCN2) is a matricellular protein with an established role in maintaining tissue and organ homeostasis. Various studies have demonstrated the importance of CCN2 in regulating cardiovascular diseases, however its role in atherosclerosis remains to be investigated.

Hypothesis:
SMC-restricted CCN2 deficiency exacerbates atherosclerosis development in murine models through the modulation of SMC phenotype switching.

Aim:
Determine the role of VSMC-derived CCN2 in regulating atherosclerosis progression.

Methods:
In this study, CCN2 was deleted in VSMCs using Cre-lox technology. To induce atherosclerosis, mice were rendered LDLR deficient via AAV8-PCSK9 injection, followed by administration of a high-fat diet for 20 weeks. Aortic atherosclerotic lesion development was then assessed along with single-cell RNA sequencing to map the molecular effects of CCN2 deficiency on the VSMCs phenotype. Gain and loss of function studies in VSMCs were performed to assess the impact of CCN2 alteration on VSMC phenotype switching.

Results:
SMC-specific CCN2 knockout (SMC-CCN2-KO) mice demonstrated exquisite susceptibility to atherosclerosis formation as evidenced by a significant increase of aortic lipid-rich plaques in aortic roots, arch, thoracic and abdominal aorta. Concomitant with this, a profound vascular inflammation was seen in SMC-CCN2-KO mice. Importantly, these phenotypic changes were associated with a dramatic shift in VSMC phenotype towards a proliferating, lipid-accumulating and macrophage-like cell phenotype. Mechanistic studies point to the requisite role of the KLF4 pathway in VSMC transdifferentiation in SMC-CCN2-KO mice, findings corroborated by cell culture experiments in which KLF4-dependent phenotypic changes were observed in CCN2-null human primary aortic VSMCs.

Conclusions:
Our findings show that CCN2 deficiency in VSMCs promotes atherosclerosis development through affecting the VSMC phenotypic transition into macrophage-like cells by activation of the KLF4 signaling pathway.
Abstract 17635: Proteomic Signatures of Diabetes-Related Coronary Heart Disease: The Atherosclerosis Risk in Communities Study
Authors: Echouffo Justin B , Ozkan Bige , Chen Jingsha , Rooney Mary R , Hoogeveen Ron C , Matsushita Kuni , Ballantyne Christie M , Selvin Elizabeth , Coresh Josef , Ndumele Chiadi E
Published: December 2023

Introduction:
The proteomic alterations that characterize coronary heart disease (CHD) in patients with type 2 diabetes are largely uncharacterized.

Hypothesis:
There are unique proteomic signatures of diabetes-related CHD.

Methods:
We quantified 4,955 plasma proteins using an aptamer-based assay (SomaLogic v4.0) in Atherosclerosis Risk in Communities (ARIC) Visit 2 (1990-92) participants. Incident CHD as defined as either myocardial infarction or fatal CHD. We used Cox regression to estimate the hazard ratios for the proteins and CHD associations, stratified by baseline diabetes status. We used Bonferroni-corrected
p
-values to adjust for multiple comparisons.

Results:
We included 9,939 individuals free of CHD (mean age: 57±5.7 years, 58% women, 23% Black adults, 14 % with diabetes). Over a median 25 years follow-up, there were 1,281 CHD events (330 among individuals with diabetes). Among 1,426 individuals with diabetes, after adjustment for confounders, 21 proteins were associated with incident CHD (p<10
-5
) (Figure, Panel A). Of these proteins, 16 were also associated with prevalent diabetes and 11 exhibited a significant interaction by diabetes status (p<0.05/21 - Figure, Panel B). The top 6 proteins uniquely associated with diabetes-related CHD include inactive tyrosine-protein kinase 7, semaphorin-4D, scavenger receptor class A member 5, kremen protein 1, and cartilage intermediate layer protein 2, and semaphorin-6A. Among those without diabetes, of the 8 proteins significantly associated with CHD (p<10
-5
), growth differentiation factor-15 was the only one that overlapped with proteins identified among individuals with diabetes.

Conclusions:
A large-scale proteomics analysis identified 20 novel proteomic markers unique to diabetes-related CHD. Our findings have the potential to shed more light on biological pathways linking diabetes and CHD.
Abstract 17640: Myocardial Infarction Quality of Care and Outcomes in Asian American Subgroups
Authors: Vijay Aishwarya , Huffman Mark D , Kandula Namratha , Lloyd-Jones Donald M , jose powell O , Yang Eugene , Goyal Abhinav , Khan Sadiya S , Shah Nilay S
Published: December 2023

Introduction:
Cardiovascular mortality differs across Asian American subgroups, but myocardial infarction (MI) hospitalization outcomes or quality of care have not been reported in these populations.

Hypothesis:
MI quality and outcomes differ among Asian Americans, with worse outcomes compared with non-Hispanic White (NHW) adults.

Methods:
Participants from 711 hospitals in the AHA Get with the Guidelines Coronary Artery Disease registry were age ≥18 years with ST-elevation MI (STEMI), identified as Asian Indian, Chinese, Filipino, Japanese, Korean, and Vietnamese, or NHW. Odds of in-hospital mortality, door-to-balloon time <90 minutes, and door-to-electrocardiogram (ECG) time <10 minutes were evaluated in each Asian American subgroup vs. NHW with sex-stratified multivariable logistic regression models, adjusted for age, CVD history, smoking, body mass index, LDL cholesterol, diabetes, hypertension, and health insurance.

Results:
Among Asian American (3,591 female; 10,660 male) and NHW (108,071 female; 224,899 male) patients with STEMI, adjusted odds of in-hospital mortality vs. NHW were higher in Korean (odds ratio [OR] 1.139, 95% confidence interval [CI] 1.021-1.271) and Vietnamese (OR 1.158, 95% CI 1.053-1.273) female patients (Figure). Likelihood of achieving door-to-balloon time <90 minutes among STEMI patients was lower in Chinese (OR 0.846, 95% CI 0.734-0.975) and Filipina (OR 0.699, 95% CI 0.616-0.793) female patients, and Chinese (OR 0.932, 95% CI 0.877-0.990), Filipino (OR 0.922, 95% CI 0.853-0.998), and Vietnamese (OR 0.890, 95% CI 0.812-0.976) male patients. Similar patterns were seen in achieving door-to-ECG time <10 minutes.

Conclusions:
STEMI outcomes and quality of care may vary among Asian American subgroups. Quality improvement programs must identify and address the factors that result in suboptimal MI outcomes and care among Asian American patients.
Abstract 17643: Pharmacist-Driven Inpatient to Tele-Clinic Transitions of Care: The PICTOC Quasi-Experiment to Reduce 30-day Readmissions in Patients With Heart Failure
Authors: Di Palo Katherine E , Manganelli Joseph , Shah Abhishek , Stark Allison , Weiss Jeffrey M
Published: December 2023

Introduction:
Successful transitional care models leverage the same clinician, typically nurses, to deliver and coordinate interventions across settings for patients with heart failure. However, pharmacists may be well-suited to lead these efforts given that medication-related issues are often drivers for 30-day readmission. We implemented a pharmacist-driven inpatient to tele-clinic transitions of care (PICTOC) program and evaluated its impact on readmissions at an academic medical center.

Methods:
Pharmacists provided hospital-based transitional care services two half-days per week between June 2020 and September 2022. They identified patients admitted for heart failure who were established at or referred to specific primary care practices. Patients were prioritized by discharge date and interventions included medication optimization, education, appointment scheduling within 14 days, and a post-discharge telemedicine visit with the pharmacist. A quasi-experimental design was used to compare the 30-day readmission rate in PICTOC group to a control group of patients who met eligibility criteria but were discharged prior to receiving the intervention. Intention-to-treat and per-protocol analyses were performed using Chi-square test.

Results:
There were 1346 patients included. The mean (SD) age was 67.0 (13.8) years, 51.3% were male and 503 patients received the PICTOC intervention. The 30-day readmission rate in the intention-to-treat group was 15.5% compared to 17.9% in the control group (p=0.25). Among the 75% of patients who attended the pharmacist telemedicine visit per protocol, the readmission rate was 13.5% (p=0.059). Patients in PICTOC group had higher rates of scheduled follow-up with primary care (59.2% vs. 53.7%, p=0.048) and cardiology (48.7% vs. 37.6%, p=0.0001). Appointment attendance with primary care was significantly higher in the PICTOC group (72.5% vs. 61.8%, p=0.0023) and trended higher with cardiology (69.4% vs. 65.9%, p=0.39).

Conclusion:
The PICTOC program improved transitional care quality and outcomes among patients with heart failure. Additional analyses of this novel care delivery model are warranted.