bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 15728: Incidence and Impact of Right Ventricular Dysfunction in the Outcomes of Septic Shock
Authors: Raavi Lekhya , Jonna Sadhana , Isha Shahin , Jenkins Anna , Hanson Abby , Balavenkataraman Arvind , Tekin Aysun , Bansal Vikas , caples sean M , Khan Syed , Jain Nitesh K , Cartin-Ceba Rodrigo , Patel Bhavesh M , Diaz Milian Ricardo , Venegas Carla P , Shapiro Anna B , Bhattacharyya Anirban , Chaudhary Sanjay , Kiley Sean P , Quinones Quintin J , Patel Neal M , Guru Pramod K , Franco Pablo M , Roy Archana , Sanghavi Devang
Published: December 2023

Introduction:
Sepsis and its associated systemic inflammatory response syndrome in the heart can lead to septic cardiomyopathy. We aim to explore new onset cardiac dysfunction in septic shock patients and its association of right heart dysfunction with hospital outcomes.

Hypothesis:
Early development of correct ventricular abnormalities due to septic shock may lead to worse hospital outcomes.

Methods:
We conducted a retrospective study of 102 patients who were hospitalized at the Mayo Clinic between August 2018 and September 2022 with septic shock and had at least one pre-sepsis echo (within one year before admission) and one post-sepsis echo (within seven days of access). Information on patient demographics, comorbidities, echo parameters, and outcomes was collected from our sepsis database and retrospective chart review. Categorical variables were described as percentages and compared by Chi-square test, and continuous variables as medians and compared using an independent sample t-test. Statistical analysis was performed using BlueSky Statistics v10.3.1.

Results:
Our study included 102 patients with a median age of 68 (55, 78) years, the majority being men (68%) and Caucasians (80%). Between pre- and post-sepsis echos, there was a noticeable decrease in LVEF (60% vs 50.5 %; p=0.002). Moreover, there was an increase in reduced RV function (31.6% vs. 62.6%, p<0.001), reduced LV function (56.5% vs. 85.2%, p=0.048), and RV dilatation (35.8% vs. 51.5%, p=0.03). There was also a noticeable decrease in IVC collapsibility of more than 50% (65.9% vs 22.9%, p<0.001). There was no significance in terms of demographics, comorbidities, and baseline vitals and labs among patients with RV dysfunction and without RV dysfunction except for a lower LVEF (49% vs 62 %, p= 0.004) and decreased >50 % IVC collapsibility (14.5% vs 48%, p=0.005) in RV dysfunction group. We found no differences in hospital mortality, ICU and hospital LOS, or mechanical ventilation requirements amongst patients with RV abnormalities in function and size.

Conclusions:
Our retrospective study shows that abnormalities in RV function and RV size are commonly observed in the initial week of septic shock. However, such RV abnormalities did not translate into worse hospital outcomes.
Abstract 15736: Coronary Angiography Alone Compared With Invasive Coronary Function Testing in Women With Ischemia and No Obstructive Coronary Artery Disease
Authors: Cigarroa Natasha , Maayah Marah J , Khokhar Arshjot , Kunnirickal Steffne , Schwann Alexandra , Latif Nida , Odanovic Natalija , Maciejewski Kaitlin , Pfau Steven , Shah Samit
Published: December 2023

Introduction:
Ischemic heart disease is a leading cause of morbidity and mortality in women. Women frequently suffer from ischemia and no obstructive coronary artery disease (INOCA) which includes phenotypes of coronary microvascular dysfunction (CMD) or coronary vasospasm (VA). Between 30-60% of women referred for invasive angiography have non obstructive coronary arteries, leaving many patients without a definitive diagnosis.

Objective:
We sought to determine the real-world diagnostic yield of invasive physiological testing in women with INOCA, and to describe downstream care regarding modifications to medical therapy based on the eventual diagnosis.

Methods:
We included 198 women who underwent either coronary angiography (CA, N=99) alone or coronary function testing (CFT, N=99) comprised of acetylcholine provocation and assessment of coronary flow reserve and the index of microcirculatory resistance. We performed a descriptive retrospective analysis of demographics, pre-procedure diagnostic testing and used logistic regression to compare the findings of angiography, post-procedure diagnosis, and changes to cardiac medications across cohorts.

Results:
The mean age was 62 ± 10 (CA alone) compared with 57 ± 10 years (CFT). Patients were mostly white (72% CA vs 79% CFT). An angiography-based diagnosis of normal coronary arteries was found in 21% CA alone (N=21) vs 48% in CFT (N=48) and non-obstructive CAD in 79% CA alone (N=78) vs 51% CFT (N=50), p<0.001. Of the women who underwent CFT, 76% (N=75) were diagnosed with a vasomotor disorder stratified by endotype of CMD 34% (n=34), VA 22% (n=22), mixed CMD/VA 10% (N=10) or endothelial dysfunction 20% (N=20). Medications were changed after angiography in 41% in the CA alone group compared to 67% in the CFT group, p<0.001; while medication changes at 30 days occurred in 22% CA alone vs 45% in the CFT group, p<0.001.

Conclusions:
Our findings demonstrate that women presenting with suspected ischemic heart disease undergoing coronary angiography often received a diagnosis of non-obstructive coronary artery disease; whereas those undergoing CFT were diagnosed with coronary vasomotor disorders. In our institution, medication changes occurred more frequently after a CFT-confirmed diagnosis.
Abstract 15746: Longitudinal Remodeling in Persistent Heart Failure With Reduced Ejection Fraction and Improved Ejection Fraction
Authors: Romero Erick , Baltodano Alexander , Patel Dev , Sellers-Porter Camryn , Deshmukh Maya , Acevedo Pablo , Shimamoto Nathan , Cadeiras Martin
Published: December 2023

Background:
Among patients with heart failure (HF) with reduced ejection fraction (HFrEF), a subpopulation improves ventricular function, HF with improved ejection fraction (HFimpEF). This study aimed to investigate the longitudinal remodeling trajectories associated with HFimpEF and with HFrEF.

Methods:
This was a retrospective cohort study, UC Davis Medical Center (2014 to 2022). The inclusion criteria included HF related ICD codes, a left ventricular ejection fraction (LVEF) ≤40%, and a B-type natriuretic peptide (BNP) ≥100 pg/mL. Longitudinal BNP and echocardiographic data were retrieved from electronic medical records. The HFimpEF group was defined as follows: an initial LVEF ≤40% with a subsequent >40% with a minimum 10% improvement after ≥3 months. Those not meeting these criteria were classified as persistent HFrEF. Longitudinal assessments were performed using linear mixed models, adjusted for baseline values.

Results:
The study included 1307 patients. The cohort median age was 65, 68% male, 57% white, with 39% developing HFimpEF. Compared to persistent HFrEF, the HFimpEF group exhibited evidence of reverse remodeling with increasing trends in LVEF, interventricular septal end diastole (IVSd), and decreasing trends in left ventricular internal dimension in systole (LVIDs) values with a
p=
<.01 between groups (Figure). However, BNP did not present significant changes over time, presenting sustained initial measurements (
p
=0.08).

Conclusion:
Patients with HFimpEF in this cohort had different longitudinal remodeling patterns compared with persistent HFrEF. The HFimpEF group had increasing trends of LVEF, IVSd and decreasing trends of LVIDs. Suggesting reverse remodeling and lower longitudinal levels of BNP.
Abstract 15773: The Forgotten Ventricle: Insight Into Dynamic Effects of Left Ventricular Assist Device Ramp on Right Ventricle Function
Authors: Garmany Armin , Stulak John M , CLAVELL Alfredo L , Behfar Atta , Rosenbaum Andrew
Published: December 2023

Introduction:
Left ventricular assist devices (LVAD) with magnetically levitated impellers have become standard due to hemocompatibility and survival profile. To optimize LVAD speeds, we previously introduced simultaneous right and left heart (RH/LH) catheterization during ramp studies. Here, we report pairing of this approach with pressure-volume (PV) assessment in a patient with a HeartMate 3 LVAD with mitral regurgitation (MR). The combined approach evaluated left ventricular (LV) hemodynamics and right ventricular (RV) PV-relationships during ramp testing.

Methods:
A 68-year-old male with ischemic cardiomyopathy, two years following HeartMate3 implantation, presented with NYHA class III symptoms. To evaluate for dyspnea, he underwent a RH/LH catheterization ramp study. RV PV-loops were created by use of a conductance catheter system, allowing creation of PV loops.

Results:
At the baseline LVAD speed of 5300 rotations per minute (RPM), right atrial pressure was elevated at 16 mmHg and pulmonary artery (PA) pressure of 26 mmHg. Left-end diastolic pressure (LVEDP) was elevated (16mmHg). Baseline cardiac index (CI) was 2.01 L/min/m
2
. Ramp testing was performed, increasing speeds from 5300 to 5800 RPM. Progressive LV unloading was observed with a 5 mmHg drop in LVEDP and a 3 mmHg drop in PA pressure. However, RV PV loop monitoring revealed a negative impact on RV contractility with the maximal elastance (Emax) slope demonstrating a 22% reduction. Furthermore, a 17% reduction in RV stroke volume was documented, while diastolic function remained unchanged. Thus, despite excellent LV offloading and diminishment of RV afterload, the significant negative impact on Emax resulted in no net increase in CI (+0.04 L/min/m
2
) during the ramp evaluation. Inotrope therapy was initiated for RV function with increased LVAD RPM to outcompete MR.

Conclusions:
While RH/LH catheterization provides a real-time perspective of the interventricular relationship during ramp, the impact of increasing LVAD speeds on RV function has yet to be directly measured. Here, the RV PV loop relationship during LVAD ramp showed that although LVAD speed increases in the setting of MR may facilitate LV unloading, a drop in RV afterload did not compensate for reduction in RV contractility.
Abstract 15796: Akt1 Y350f Mutation: A Protective Mechanism Against Pulmonary Hypertension, Suppressing Endothelial-to-Mesenchymal Transition in vivo and in vitro
Authors: BHARTI DINESH , Valuparampil Varghes Mathews , James Joel , Yazdi Alhan M , Rafikova Olga , Rafikov Ruslan
Published: December 2023

Background:
Pulmonary hypertension (PH) is a life-threatening condition characterized by elevated blood pressure in the lungs due to narrowed arteries. Endothelial-to-mesenchymal transition (EndMT) contributes to enhanced proliferation and metabolic changes in the pulmonary arteries of PH patients. Our previous reports have highlighted the role of Akt nitration at tyrosine 350 (Y350) residue in promoting proliferation and metabolic switch in PH models. To investigate the protective potential of inhibiting Akt nitration, we developed a mouse model with a mutation of Akt Y350 to phenylalanine (Y350F), preventing nitration and activation of Akt.

Hypothesis:
We hypothesized that Akt1 Y350F mutant mice would be protected in preclinical PH models due to inhibited EndMT.

Methods:
Both mutant Y350F and wild-type Akt1 mice were treated with Sugen5416 (20mg/kg/week i.p.)/hypoxia (10% O2) (Su/Hx) for four weeks to explore pathological mechanisms. Endothelial cells were isolated for in vitro evaluation under EndMT inducers, including Sin-1 chloride and TGF-β1.

Results:
The wild-type Su/Hx model exhibited vascular remodeling, increased right ventricular systolic pressure (RVSP) (p<0.001), and right ventricular hypertrophy. In contrast, the Akt Y350F mutant model displayed significant protection, with reduced vascular remodeling, pulmonary pressure, and right heart hypertrophy. Akt nitration-induced EndMT markers, TGF-β1 (p<0.05) and TWIST1 (p<0.01), were elevated in wild-type Su/Hx lung tissue. However, the Akt Y350F mutation prevented Akt activation and diminished EndMT markers in the Akt1 Y350F Su/Hx lungs. In isolated cells and lung tissue, induction of EndMT resulted in a progressive PH phenotype, while Akt inhibition exhibited a protective role against PH progression in the Akt Y350F mutant model.

Conclusion:
Inhibition of Akt nitration through the Y350F mutation restricts vascular remodeling and halts EndMT both in vivo and in vitro. Our findings suggest that strategies targeting Akt nitration could be effective in controlling PH.
Abstract 15804: Intervention to Improve Self-management of Blood Pressure for Low-Income Black Patients With Severe Hypertension
Authors: Tharakan Anna , Biola Holly , Allen Jada , Desai Devan , Gaines Megan , Gupta Rohan , Johnson Camryn , Nguyen Jennifer , Sai Ashna , Surzykiewicz David , Villanueva Aiyana , Wambugu Vivien , Wang Velda , Yoon Elliot , Granger Bradi B
Published: December 2023

Background
Hypertension is a leading cause of preventable mortality and morbidity and is disproportionately represented among minority populations. Despite proven interventions outlined in practice guidelines, only 48% of patients who are diagnosed with hypertension have their condition controlled. In a southeastern US county, the prevalence of hypertension is 42%, with a strong association with race, suggesting opportunities to intervene at a neighborhood level to reduce hypertension disparities and improve overall population health.
Aims
To improve access to care through targeted opportunities for self-management of blood pressure (BP).

Methods:
This quality initiative used a pre-post evaluation design. We identified Black low-income patients with uncontrolled hypertension (SBP
>
160 mmHg and/or DBP
>
100 mmHg) from a local federally qualified health center (FQHC). Trained student ambassadors provided telephone outreach, BP cuffs, and goal setting on AHA Essential 8 for 4 months. Follow-up occurred at 7 months.

Results:
Among Black participants (n=345), average age was 55.4 years (SD 8.7), and a majority were male (n=173, 50.1%) and uninsured (n=159, 46.1%). Engagement in calls occurred for 67.8% (n=234) of the cohort; cuff distribution was 22.9% (n=79); and AHA Essential 8 goal setting occurred for 64 patients. BP improved for 40% of the cohort (mean pre: 168/98 mmHg, mean post: 150/89 mmHg;
p
<0.0001). Of the cohort reached, 33% expressed social needs such as food insecurity, housing, and medication costs.

Conclusion
Findings suggest that telephone outreach with student ambassadors successfully improves patient engagement and reduces blood pressure, on average.
Abstract 15814: Imaging Local and Systemic Reactive Oxygen Species After Ischemia-reperfusion Injury in Swine With Multimodal
18
F-ROStrace PET/CT and CMR
Authors: Swago Sophia , Thompson Elizabeth W , Bhattaru Abhijit , Moon Brianna F , Ferrari Giovanni , Castillero Estibaliz , Gallagher Evan , Mcmanus Meagan , Ferrari Victor A , Gorman Robert , Tschabrunn Cory , Mach Robert H , Karp Joel S , Witschey Walter R , Bravo Paco E
Published: December 2023

Introduction
Reperfusion injury after myocardial infarction (MI) can cause additional tissue damage and is associated with adverse outcomes, and inflammation of extra-cardiac tissue may occur post-MI. In this study, we used positron emission tomography (PET) radiotracer [18F]ROStrace to image reactive oxygen species (ROS) in myocardium and in extra-cardiac tissues in a swine model of subacute ischemia-reperfusion injury.

Methods
The mid left anterior descending coronary artery was occluded in three swine for 90 minutes, followed by reperfusion. Baseline and post-MI ROStrace data were acquired 3 days post-MI on the long axial field-of-view PennPET Explorer PET/CT system. A [82]Rb scan was acquired to calculate myocardial blood flow (MBF). Regions of interest (ROIs) were drawn in brain, lungs, bone marrow, spleen, skeletal muscle, myocardium (baseline) and infarcted and non-infarct myocardium (post-MI). ROStrace fractional uptake rate (FUR) was calculated in all ROIs. Cardiac FUR was corrected for MBF. Paired T-tests and Cohen's d effect size (ES) were used to evaluate the effect of MI on ROStrace activity in cardiac and extra-cardiac tissues. Cardiac MRI was done to quantify infarct size.

Results
In extra-cardiac tissues, MI had a nonsignificant medium effect on ROS in bone marrow (ES = 0.54, p = 0.45) and spleen (ES = 0.60, p=0.41), and a nonsignificant large effect in skeletal muscle (ES = 1.24, p = 0.17). No effect was seen in brain and lungs. In the heart, MI had a significant large effect on ROS in the region of the infarct, compared to baseline (ES = 3.84, p = 0.02) (Fig. 1). Infarct size on late gadolinium enhanced MRI ranged from 16.73 to 33.62% of the myocardium.

Conclusion
For the first time, systemic and local effects on ROS after MI were directly imaged using whole-body [18F]ROStrace PET. We found that ROS are increased in the infarcted myocardium in the subacute phase, and MI leads to moderate-to-large effects in ROS levels in hematopoietic tissues and skeletal muscle.
Abstract 15818: Association of Clonal Hematopoiesis of Indeterminate Potential With Incident Heart Failure With Preserved Ejection Fraction
Authors: Honigberg Michael C , Reiner Alex P , Roberts Mary , Kooperberg Charles , Desai Pinkal , Bick Alexander G , Natarajan Pradeep , Manson JoAnn E , Whitsel Eric A , Eaton Charles
Published: December 2023

Introduction:
Clonal hematopoiesis of indeterminate potential (CHIP) is the age-related expansion of blood cells with somatic mutations, most commonly in
DMNT3A
,
TET2
, and
ASXL1
. CHIP is a risk factor for coronary heart disease as well as heart failure (HF). Experimental HF models suggest a role of CHIP pro-inflammatory myeloid cells on cardiac dysfunction via fibrotic remodeling and hypertrophy. However, whether CHIP associates with incident HF with preserved ejection fraction (HFpEF), HF with reduced ejection fraction (HFrEF), or both is currently unknown.

Hypothesis:
We hypothesized that CHIP is more strongly related to HFpEF than HFrEF.

Methods:
We studied a multiethnic sample of postmenopausal women without prevalent HF from the Women’s Health Initiative (WHI). Whole genome sequencing was performed through the NHLBI TOPMed Program, and CHIP was detected based on 74 pre-specified myeloid driver mutations. Participants were followed through March 2020 with physician adjudication of HFrEF and HFpEF. Cox models tested the association of CHIP with incident HFpEF and HFrEF with adjustment for demographic/clinical risk factors and inverse probability weighting to account for the TOPMed sampling scheme.

Results:
Among 5,214 women, the mean age was 62 years, and 7.8% had CHIP. Over a median follow-up of 15 years, age-adjusted HFpEF incidence rates were 5.86 (95%CI 5.63-6.10) vs. 3.72 (95%CI 3.68-3.77) per 1,000 person-years among CHIP carriers vs. non-carriers. After multivariable adjustment, CHIP was associated with a 42% increased risk of incident HFpEF (HR 1.42, 95%CI 6-91%;
P
=0.02). In contrast, there was no evidence of association between CHIP and HFrEF (
Table 1
). HFpEF was more strongly associated with
TET2
CHIP (HR 2.50, 95%CI 1.54-4.06;
P
<0.001) than with
DNMT3A
or
ASXL1
(
Table
1
).

Conclusions:
CHIP, especially
TET2
CHIP, is associated with incident HFpEF. This finding has potential precision medicine implications for HFpEF prevention and treatment.
Abstract 15828: Variations in the Use of Catheter Ablation for Atrial Flutter Among US Adults Using Nationwide Inpatient Sample (NIS) Database
Authors: Benjamin Patrick , Oyenubi Olamide , Stan Andreea-Constanta , Salami Joseph A , Huang Jiannan
Published: December 2023

Introduction:
Atrial flutter is one of humans' most common cardiac arrhythmias. Catheter ablation is the definitive treatment for typical atrial flutter because of a very high success (>95%) and low complication rate. Therefore, we explored variations in the use of catheter ablation for atrial flutter among US adults.

Methods:
We used the 2017-2019 National Inpatient Sample (NIS) for this analysis. Multivariable logistic regression analysis was used to assess factors associated with catheter ablation among patients with atrial flutter in the US.

Results:
Of the 1406220 adults hospitalized with a diagnosis of atrial flutter, 66825 (4.75%) underwent ablation for atrial flutter. Blacks were less likely to undergo ablation for atrial flutter compared to Whites (AOR=0.91; 95% CI: 0.85-0.99, P = 0.01). Similarly, patients with Medicare (AOR=0.88; 95% CI: 0.83-0.92, P=0.00), and Medicaid insurance (AOR=0.80; 95% CI: 0.74-0.87, P=0.00) were less likely to have catheter ablation for aflutter compared to those with private insurance. Other significant predictors of the likelihood of getting an ablation included younger age 0.98 (95% CI: 0.97-0.98, P=0.00), and lower co-morbidity burden ( class II with AOR of 0.65; 95% CI: 0.62-0.69 and Class III with AOR of 0.43; 95% CI: 0.41-0.46 compared to class I). No gender disparity was observed in this analysis, females had an AOR of 0.96 (95% CI: 0.92-1.00)

Conclusions:
Findings highlight significant racial and insurance-related disparities in access to catheter ablation for atrial flutter. Addressing social and structural issues underlying these disparities is critical for achieving equitable outcomes for patients with atrial flutter.
Abstract 15832: Racial Differences in the Utilization and Outcomes of Transcatheter Aortic Valve Replacement
Authors: Antia Akanimo , Onuegbu Chinwendu , Alviar Carlos L
Published: December 2023

Introduction:
The use of transcatheter aortic valvular replacement (TAVR) improves outcomes in patients with aortic stenosis (AS). However, there is limited data describing racial disparities in TAVR use. Our aim was to evaluate outcomes according to racial groups and TAVR use in the national inpatient sample (NIS).

Methods:
We identified all patients undergoing TAVR between 2016 - 2020 from the NIS of the Health Care Utilization Project database. Patients were classified according to ethnic groups as white, black, Hispanic, and Asians. Outcomes included TAVR utilization by ethnic group, mortality, respiratory failure rates, cardiogenic shock, cardiac arrest, and hospital length of stay (H-LOS). Multivariate analysis was performed adjusting for age, sex, cardiovascular comorbidities, and socioeconomic status.

Results:
From 296,740 patients who underwent TAVR, 89.5% were white, 4.24% were black, 4.9% were Hispanic, and 1.39% were Asian. Blacks had higher rates of CHF, chronic kidney disease, peripheral vascular disease, obesity, and anemia but lower rates of myocardial infarction, CABG, pacemaker placement and PCI. Hispanic patients showed higher rates of AKI, while Asian patients had higher rates of DM. Blacks had lower adjusted mortality rates compared to whites (aOR: 0.56; CI 0.35 - 0.88 p=0.014). Respiratory failure rates (aOR: 0.82; CI 0.68 - 0.98, p=0.031) and H-LOS (5.2 days vs 3.7 days) were higher in black patients. Whites had a steeper increase in TAVR use compared to other groups during the study period. Patients with AS undergoing TAVR had significant lower adjusted mortality (aOR: 0.95; CI 0.92 - 0.98 p=0.005).

Conclusion:
White patients are most likely to receive TAVR compared to other ethnic groups. Such differences in TAVR utilization by ethnic group should be studied further to decrease healthcare disparities
Abstract 15834: The Utility of Intra-Operative Coronary Doppler Profiles in Predicting Early and Late Major Adverse Cardiovascular Events After Arterial Switch Operation
Authors: Howell Alison J , Nield Lynne E , Kadowaki Sachiko J , Tarafdar Oishika , Mertens Luc L , Fan Chun-Po , Honjo Osami
Published: December 2023

Introduction:
Coronary artery transfer is the most important technical point in the arterial switch operation (ASO). Intra-operative echocardiography identifies aberrancies in coronary artery Doppler profiles guiding immediate surgical management.

Objective:
We sought to determine whether abnormal intra-operative coronary artery Doppler profiles are associated with major adverse cardiovascular events (MACE; death, transplantation, heart failure, arrhythmia, need for coronary re-intervention) following ASO at 30-days, 5 & 10 years.

Methods:
Single centre retrospective review of patients undergoing ASO between 2009 - 2022. Transesophageal or epicardial intra-operative coronary artery Doppler profiles were analysed. Patient variables were abstracted from records. Freedom from MACE was estimated using Kaplan-Meier methods.

Results:
347 patients were included. Coronary anatomy was usual (1LCx2R) in 237 (68%), single sinus ostia in 24 (7%), intramural in 14 (4 %). Overall 30-day MACE was 11.2% [8.3%, 15.1%], increasing to 25% [12.1, 47.4%] with single sinus ostia & 35.7% [16.7%, 65.7%] with intramural. Overall 5 & 10-year MACE was 16.5% [12.9, 20.9%], 33.8% [18.5%, 56.4%] with single sinus ostia & 50.0% [27.8%, 77.1%] with intramural. A higher probability of MACE was seen with coronary Doppler reverse flow, absence of normal pattern (Table 1) and a higher peak velocity (Figure 1). Overall 30-day mortality was 1.2% [95%CI 0.4%, 3.0%] and at 5 & 10 years was 6.5% [4.3%, 9.8%].

Conclusions:
Intra-operative abnormal coronary artery Doppler profiles during ASO may identify those at highest risk of early and late adverse events, guiding follow-up surveillance strategies.
Abstract 15846: Impaired Contraction and High Susceptibility to Arrhythmias in a Mouse Model of Desmoplakin-Mediated Arrhythmogenic Cardiomyopathy
Authors: Camors Emmanuel M , Orgil Buyan-Ochir , Alberson Neely , Purevjav Enkhsaikhan , Towbin Jeffrey A
Published: December 2023

Introduction:
Desmoplakin (DSP) is a key protein for cardiac myocyte cell-to-cell adhesion that connects the desmosomes present in intercalated discs to the cytoplasmic network of desmin intermediate filaments. Pathogenic variants of the human
DSP
gene often lead to left ventricular (LV)-dominant and biventricular forms of arrhythmogenic cardiomyopathy characterized by a dilated LV, arrhythmias, and an elevated risk of sudden cardiac death. Nonetheless, the pathophysiological pathways triggered by
DSP
variants remain unknown.

Hypothesis:
We hypothesized that
DSP
pathogenic variants modify cardiomyocyte excitation-contraction coupling leading to life-threatening ventricular arrhythmias.

Methods:
We created a novel knock-in mouse model based on the human
DSP
p.S2859LfsX5 variant that leads to a murine protein truncated from its last 9 amino-acids. We compared one-year-old sedentary heterozygous (Dsp
+/-
) animals to WT littermates and defined histologic, cellular, and molecular outcomes of the variant.

Results:
Western blotting revealed 50% Dsp reduction (N= 5 hearts/group;
P
< 0.05) in mutant right ventricle (RV) indicating mutant protein instability. Histologic assessments of Dsp
+/-
hearts revealed LV chamber enlargement and RV wall thinning in the absence of fibrosis and lipid infiltration. Dsp
+/-
myocytes isolated from LV and RV free walls and field stimulated at 3 Hz exhibited 30-40% reduction in sarcomere shortening (n= 17-25 myocytes/ventricle/3-4 hearts/group;
P
< 0.05), while their Ca
2+
handling properties remained normal. Pacing of Dsp
+/-
isolated myocytes (LV and RV) in the presence of (100 nmol/L) isoproterenol provoked a 20-30% increase in Ca
2+
release due to sarcoplasmic reticulum Ca
2+
overload (n= 15-20 myocytes/ventricle/3-4 hearts/group;
P
< 0.05). Finally, surface ECGs showed that activation of the sympathetic pathway (isoproterenol + caffeine) in 6-month-old Dsp
+/-
mice increased mutant heart susceptibility to ventricular arrhythmias.

Conclusions:
The pathogenic variant p.S2859LfsX5 promotes biventricular dysfunction due to the loss in myocyte contraction capacity and catecholaminergic-mediated ventricular arrhythmias from cardiomyocyte Ca
2+
overload.
Abstract 15872: Development and External Validation of a De Novo Simulation Model to Inform Implementation Strategies for Guideline-Directed Medical Therapy of Heart Failure With Reduced Ejection Fraction
Authors: Foote Julia H , Pandey Ambarish , Agarwal Anubha , Bellows Brandon K , DeJong Colette , Hsue Priscilla Y , Kazi Dhruv S
Published: December 2023

Introduction
Guideline-directed medical therapy (GDMT) for heart failure with reduced ejection fraction (HFrEF) includes four medication classes and improves survival. However, uptake and adherence to GDMT remain low. Simulation models to project long-term benefits can inform ongoing trials of GDMT implementation strategies (such as a polypill). As such, we sought to develop and validate a mathematical model of HFrEF and GDMT treatment.

Methods
We developed a state-transition, Markov model to simulate hospitalizations, urgent care visits, and cardiovascular and non-cardiovascular death among patients with HFrEF on 0, 2, 3, and 4 GDMT drugs. Input parameters were derived from trials, epidemiologic cohorts, national surveys, and published literature. External validation compared model-projected all-cause mortality with data from the Seattle-HF model and three major HFrEF trials (eplerenone in EMPHASIS-HF, sacubitril/valsartan in PARADIGM-HF, and dapagliflozin in DAPA-HF). Goodness-of-fit was assessed by root-mean-square-error (RMSE), with RMSE ≤ 5.0 considered to be a good fit.

Results
In external validation, the model accurately replicated 5-year survival curves from the Seattle-HF model among treatment-naïve patients age 65 years (RMSE 1.9), 75 years (RMSE 1.2), and 85 years (RMSE 1.9). Model projections demonstrated good fit among individuals on various combinations of GDMT, with RMSE 0.6-2.8 across all combinations tested (Figure). For a 65-year-old with HFrEF, our model projected a mean survival of 6.3 years without GDMT, increased by 2.5 years on 2-drug, 3.4 years on 3-drug, and 4.7 years on 4-drug GDMT.

Conclusion
Our model replicated survival outcomes with GDMT in HFrEF and demonstrated improved survival associated with more classes of GDMT. Future work will project the long-term health and economic impacts of implementation strategies to improve GDMT uptake and adherence, incorporating healthcare costs and quality-of-life measures.
Abstract 15923: Sexually Dimorphic Heart Phenotypes in Mice Lacking Chromatin Factors in Cardiomyocytes
Authors: Knutson Andrew K , Avelar Abigail , Shohet Ralph V
Published: December 2023

Introduction:
Sex differences in cardiovascular disease have been attributed to differences in lifestyle or sex hormones; less is known of genetic components that cause differences in heart disease between men and women. We have characterized a role for the ZMYND8 chromatin reader in maintaining cardiac function through modulation of enhancer activity in cardiomyocytes. ZMYND8 has been reported to interact with H3K4 histone demethylases KDM5C and KDM5D, which are encoded from genes residing on sex chromosomes (
Kdm5c
on X and
Kdm5d
on Y). KDM5C and KDM5D have diverged over millions of years of sex chromosome evolution and their functional congruency is unknown.

Hypothesis:
We hypothesize that sex differences in cardiovascular disease are due, at least in part, to differences in functionality of genes residing on the sex chromosomes.

Methods:
We constructed
Zmynd8-cKO
mice using the cardiomyocyte-specific

Myh6-Cre
Tg/0

line and an established

Zmynd8
flox

allele. We also introduced a

Kdm5c
flox

allele to the

Myh6-Cre
Tg/0

line to generate
Kdm5c-cKO
females and
Kdm5c-cKO
hemizygous males. These mice were evaluated by lifespan analyses, echocardiography, and molecular analyses (RNA-seq and ChIP-seq).

Results:
While both male and female
Zmynd8
-
cKO
mice develop enlarged hearts, reduced contractility, and illegitimate expression of certain genes normally found in skeletal muscle, female mice have a 10% reduction in lifespan compared to males; this sex difference in lifespan is not seen in Cre-only mice. We tested the necessity for
Kdm5c
in cardiomyocytes and found that its deletion also leads to premature death in a dosage dependent manner compared to Cre-only mice. Interestingly,

Myh6-Cre
Tg/0
; X
5c-flox
/Y

hemizygous males have a 20% shorter lifespan than

Myh6-Cre
Tg/0
; X
5c-flox
/X
+

heterozygous females, suggesting differences between KDM5C and KDM5D functionality.

Conclusions:
Our results provide evidence of sexually dimorphic heart defects linked to chromatin regulators, including a gene-pair found on the sex chromosomes. We are deliniating the molecular underpinnings of these observations including changes to histone marks and gene expression in these knockout models.
Abstract 15926: Left Atrial Pressure and H
2
FPEF Score in Patients With Atrial Fibrillation Who Underwent Catheter Ablation
Authors: Park Jong Sung , Kim Daehoon , Kim Moon-Hyun , Park Je W , Yu Hee Tae , Kim Tae-Hoon , Uhm Jae-sun , JOUNG BOYOUNG , LEE Moon Hyoung , Pak Hui-Nam
Published: December 2023

Introduction:
Heart failure with preserved ejection fraction (HFpEF) is a common comorbidity in atrial fibrillation (AF) patients and contributes to AF progression and stroke risk.

Hypothesis:
We explore the hemodynamic effects of left atrial pressure (LAP), which was directly measured during AF catheter ablation (AFCA), on HFpEF based on the H
2
FPEF score.

Methods:
We included 1,426 patients (73.3% male, median age, 61.0 [54.0-68.0] years; 45.7% persistent AF) who underwent AFCA, LAP measurements at both AF and sinus rhythm (SR), echocardiogram, and H
2
FPEF score, and excluded the patients with EF <50%. We divided patients into low-risk (< 6 points) and high-risk (
≥
6 points) HFpEF groups and measured LAP-mean depending on heart rates 90, 100, 110, and 120 bpm during right atrial pacing (Pace-HR) and isoproterenol (ISO-HR) infusion in all patients.

Results:
The LAP-mean was sequentially and significantly higher according to the H
2
FPEF score (p<0.001) and had an independent association with the high-risk HFpEF group (OR 1.37 per 10mmHg increase [1.13-1.67], p=0.001). LAP-mean increased significantly with increasing Pace-HR (90-120 bpm, 10.4 to 11.6 mmHg, p<0.001) but decreased with ISO-HR (90-120 bpm, 10.2 to 8.1 mmHg, p<0.001). In patients with paroxysmal AF, LAP-mean[AF] was significantly higher than LAP-mean[SR] (p<0.001), but not in those with non-paroxysmal AF (p=0.557). In patients with paroxysmal AF, ΔLAP-mean[Pace-HR, 120-90bpm] was significantly higher than that of non-paroxysmal AF (p<0.001).

Conclusions:
LAP is independently associated with H
2
FPEF score and has inverse rate-dependent response depending on pacing or ISO infusion. Higher increase of LAP during AF or higher Pace-HR contributes to more severe symptoms in patients with paroxysmal AF than in non-paroxysmal AF.
Abstract 15927: Polyunsaturated Fatty Acid Levels and Their Relationship With Peak Exercise Measures in HFpEF
Authors: Prasad Cheshta , Campain Joseph , Helmering Joan , Hale Clarence , Chen Michelle , Veniant-Ellison Murielle , Malhotra Rajeev , Lewis Gregory
Published: December 2023

Background:
Polyunsaturated fatty acids (PUFAs) regulate the inflammatory cascade and have been implicated in potential pathologic and therapeutic roles in heart failure with preserved LVEF (HFpEF). The purpose of this study was to explore the relationship between plasma levels of omega-3 (ω-3) fatty acids and invasive hemodynamic profiles characteristic of early HFpEF.

Methods:
In a single-center referral cohort undergoing evaluation for exertional dyspnea and suspected HFpEF, we assayed ω-3 concentrations in plasma by liquid chromatography. We derived an ω-3 score by summing Z-scores of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). Linear regression was used to relate plasma ω -3 levels to simultaneously collected physiologic data from cardiopulmonary exercise testing (CPET) with invasive catheterization.

Results:
588 patients (52% female, age 62 ± 12 years, BMI 30 ± 6 kg/m
2
, peak oxygen uptake (VO
2
) 15.5 ± 5.1 mL/min/kg [76 ± 20% predicted], NTproBNP 118 [33 - 405] pg/mL) were studied. Median ω -3 concentrations were 72 [46 - 107] pg/mL for EPA and 315 [225 - 457] pg/mL for DHA. Female sex and increased age were associated with higher levels of ω-3 fatty acids (
Table
, p=0.03). After adjustment for age, sex, and BMI, a higher ω-3 score was associated with greater exercise capacity measured by peak VO
2
(p<0.001) and peak workload (p<0.001) along with an increase in peak exercise peripheral O
2
extraction (CavO
2
; p < 0.001). Notably, increased ω-3 score was associated with lower supine pulmonary capillary wedge pressure (PCWP; p=0.03), PCWP to cardiac output (CO) slope during exercise (p = 0.009), and NTproBNP (p < 0.001).

Conclusion:
These data demonstrate that circulating ω-3 fatty acid levels are associated with exercise capacity and both central cardiac and peripheral function in HFpEF. Further studies are needed to unravel the relationship between modulation of plasma PUFAs and rest and exercise hemodynamic profiles of HFpEF.
Abstract 15936: Prospective Evaluation of Anti-Ro Pregnancies Supports the Utility of Ambulatory Fetal Heart Rate Monitoring in Detecting Fetal Atrioventricular Block
Authors: Cuneo Bettina F , Abuhamad Alfred , Copel Joshua , Cumbermack Kristopher , Doan Tam , Donofrio Mary T , Gropler Melanie , Haxel Caitlin , Hogan Whitnee , Howley Lisa , Joffe Gary , Kaplinski Michelle , Kohari Katherine , Krishnan Anita , Levasseur Stephanie , Lindblade Chris , Makhoul Majd , Matta Jyothi , Moon-Grady Anita J , Owens Sonal , Paul Erin A , Pinto Nelangi , Phoon Colin K , Satou Gary M , Sinkovskaya Elena , Killen Stacy , Strainic James , Fraser Nicola , Masson Mala , Clancy Robert , Buyon Jill
Published: December 2023

Introduction::
The management of anti-Ro/SSA positive pregnancies is challenging because fetal atrioventricular (AV) block is rare and fetal echo seldom detects reversible injury.

Hypothesis:
We hypothesized that ambulatory fetal heart rate/rhythm monitoring improves detection of fetal AV block when compared with echo.

Methods:
Anti-Ro antibody subjects from 21 US centers at less than 20 weeks of gestation were risk stratified into high and low anti-Ro60 and 52 titers at the New York University (NYU) core laboratory. Low titer was defined by previous NYU data demonstrating no fetal AV block in subjects with anti-Ro60
and
52 less than 1000 arbitrary units per mL. High titer subjects performed 3x/day fetal heart rate/rhythm monitoring and underwent weekly or bi-weekly surveillance fetal echos at 18-26 weeks of gestation. Low titer subjects underwent site-specific surveillance. Abnormal fetal heart rate/rhythm monitoring prompted urgent diagnostic fetal echo. All infants received electrocardiograms.

Results:
We enrolled 405 subjects (fig). None of the 150 (37%) low titer subjects developed fetal AV block. Of 255 high titer subjects, 241 completed surveillance. High titer subjects monitored 44,187 times; 37 (0.08% ) monitoring episodes were deemed abnormal. Urgent fetal echos of the 37 diagnosed 9 with fetal AV block (7 with 2° AV block), 14 with atrial ectopy and 14 with normal rhythms. No fetal AV block, endocardial fibroelastosis or cardiac dysfunction was detected in the 871 surveillance fetal echoes of high titer subjects following normal FHRM. No fetus developed AV block after the surveillance period; one baby had transient prolonged PR interval, which resolved spontaneously.

Conclusions:
This prospective study suggests that ambulatory fetal heart rate/rhythm FHRM is superior to echo surveillance for fetal AV block, and antibody titers are useful in risk stratification of anti-Ro positive pregnancies.
Abstract 15958: Obstetrical History That Includes Adverse Pregnancy Outcomes (APO) Are Not Incorporated Into the Creation of Cardiovascular Risk Screening in Adults
Authors: Guerrero Kerly M , Wesley Shaun , Mishiyeva Medina , Xiao Weirui , Wolfe Diana S , Bernstein Peter , Patel Krishna K , Thornburg Loralei
Published: December 2023

Introduction:
Cardiovascular disease (CVD) is a major contributor to maternal morbidity and mortality and is the leading cause of death for women/assigned female at birth (AFAB) people in the US. People who experience metabolic and hypertensive complications in pregnancy are at an increased risk of hypertension and CVD later in life. ACC/AHA have published clinical guidelines, which includes the use of the ASCVD risk estimator, to identify patients that may benefit from treatment with primary prevention. Our objective was to determine how often OBHx was included in the underlying primary literature that was utilized to create the current CVD screening guidelines.

Methods:
This is a descriptive study of the cited works, including original research and guidelines, used to develop the 2018 guidelines for the use of risk assessment tools for ASCVD and the 2019 primary prevention of CVD guidelines. Original research citations were analyzed for identification of OBHx. Articles that included OBHx were analyzed for identification of Adverse Pregnancy Outcomes (APO), specific risk factors including preeclampsia/gestational hypertension (GHTN), fetal growth restriction (FGR), preterm delivery (PTD), gestational diabetes (GDM) and peripartum cardiomyopathy (PPCM). We further assessed discussion of OBHx within the articles as: cursory (1-2 sentences), moderate (3-5 sentences), or extensive (>5 sentences).

Results:
Of the 58 articles included, more than half included AFAB/women, 37 (63.8%), although how sex/gender was assigned was not delineated. Of these only 3 (5.2% of total) included OBHx. In 2 of the studies OBHx was identified by maternal recall, while 1 study performed a chart review. Of the 3 studies that included OBHx, 2 (66.6%) included history of preeclampsia/GHTN and PTD. FGR and GDM were each identified in 1 article. None of the articles included PPCM. An extensive discussion of APO risk factors was included for 2, while 1 study had a moderate discussion.

Conclusions:
Most of the data used to create the primary prevention of CVD guidelines provide very little information regarding OBHx. This may lead to an underestimation of CVD risk in AFAB people and potentially fail to identify those that may benefit from treatment for primary prevention of CVD.
Abstract 15962: Validation of the Senescence-Associated Secretome to Predict Mortality in Patients With Degenerative Aortic Valve Stenosis
Authors: Mas-Peiro Silvia , Zanders Lukas , Rasper Tina , Berkowitsch Alexander , Dimmeler Stefanie , Zeiher Andreas M
Published: December 2023

Introduction:
The senescence-associated secretory phenotype (SASP) is a potential driver of age-related risk reflecting advanced biological aging. Circulating SASP components include pro-inflammatory cytokines, growth modulators and matrix remodelling proteases. Aortic valve stenosis (AVS) is the prototypical inflammatory age-associated cardiovascular disease.

Hypothesis:
To identify circulating SASP components with an impact on prognosis in elderly pts with AVS.

Methods:
In a derivation cohort (n=120), circulating levels of 24 SASP components were measured using Luminex Multiplex ELISA, before undergoing TAVR. ROC curves and Youden-index derived optimal cut-off values were used to assess the predictive power of each SASP for long-term mortality. In a validation cohort (n=198), the significant predictors of mortality identified in the derivation cohort, as well as a panel of 3 independent predictors in multivariate analyses, were prospectively validated.

Results:
In the derivation cohort, 9 out of 24 SASP components significantly predicted mortality in univariate analyses with AUC>0.62; only 3 (GDF-15, ICAM-1, and osteoprotegerin) remained independent predictors in multivariate analyses (all p<0.03). All 3 were confirmed as significant independent predictors of mortality in the validation cohort (see AUC curves). After adjustment for clinical parameters, a score based on the cumulative number of these 3 SASP components showed a substantial increase in long-term mortality after TAVR for each additional positive marker (see KM-curves).

Conclusions:
This study validates high levels of 3 SASP components reflecting different pathophysiological pathways of senescence as independent predictors of long-term mortality in AVS. Their cumulative occurrence provides a deeply improved discrimination power and, may serve as a much needed risk stratification tool in elderly patients with AVS undergoing TAVR.
Abstract 15993: The Association of Aspirin With and Without Statin on Cardiovascular Outcomes in Primary Prevention Patients With Diabetes Mellitus
Authors: Muluk Pallavi , Zhu Jianhui , Thoma Floyd W , Gulati Martha , Hay Eli , MARROQUIN Oscar C , Makani Amber , Virani Salim S , Ballantyne Christie M , Mulukutla Suresh R , Saeed Anum
Published: December 2023

Background:
The role of aspirin in primary prevention of ASCVD amongst high-risk individuals with diabetes mellitus remains unclear. We investigated aspirin use with and without statin and its association with future ASCVD events in a cohort of real-world primary prevention patients with diabetes mellitus.

Methods:
Primary prevention patients with diabetes were stratified based on HbA1c levels (6.5-7%, 7-9%, >9%) and 10-year ASCVD risk (High-risk [≥20%]). Aspirin use was defined as no use, seldom used (<30% of the time), sometimes used (≥30% - < 70% of the time), and often used (≥70% of the time). Cox regression assessed HRs of myocardial infarction (MI), stroke, and mortality with aspirin use.

Results:
Of 79, 597 patients with diabetes, 44.6% were classified as high-risk. These patients showed highest utilization of aspirin (45.7%) and statin (44.9%). Compared to high-risk patients with diabetes and an HbA1c of >9% on both a statin and an aspirin, those on statin alone had higher risk of MI [HR MI 1.74 (1.44-2.212), p <0.001], ischemic stroke [HR STROKE 2.52 (1.92-3.29), p <0.001], and mortality [HR 1.67 (1.27-2.19), p <0.001] (Table). Aspirin use alone was associated with higher risk of MI [HR 3.11 (2.42-4.00), p <0.001], ischemic stroke [HR 3.12 (2.08-4.67), p <0.001], and mortality [HR 3.77 (2.71-5.23), p < 0.0004] in the high-risk population with HbA1c >9% (Table). At all A1c levels, patients on no statin or aspirin were at significantly higher risk for MI, stroke, and mortality (Table). In high-risk patients with an HbA1c >9%, ASA use ≥ 70% resulted in significantly lower risk of MI [HR 0.58 (0.49-0.69), p<0.001)], ischemic stroke [HR 0.36 (0.28-0.46), p<0.001] and mortality [HR 0.52 (0.42-0.66), p<0.001].

Conclusion:
Low dose aspirin may play a role in prevention of ASCVD events in high-risk patients with diabetes. Future studies can clarify the risk-benefit ratio of using aspirin with statin in patients with poor glycemic control for primary prevention of ASCVD events.