bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 14148: Transcatheter Mitral Valve Replacement: A Single Center Tertiary Care Experience
Authors: Vashistha Kirtivardhan , Tobaa Amel , Elhamdani Adee , Khalif Adnan , Doyle Mark , khalil ramzi
Published: April 2024

Background:
Transcatheter mitral valve replacement (TMVR) using transcatheter aortic valves is considered an advanced structural heart procedure performed at comprehensive valve centers in patients with degenerated mitral valve prostheses. We present our single-center experience of patients undergoing Valve in Valve (ViV) and Valve in Ring (ViR) TMVR.

Methods:
We identified patients who underwent the TMVR procedure at our center from 1/1/2017 to 12/31/2020. We analyzed baseline characteristics, STS-PROM score, functional status (NYHA and KCCQ), baseline laboratory values, echocardiographic parameters (including LVEF, MV area, gradient, grading of MS and MR was collected. Follow-up data on functional status, echocardiographic parameters, and mortality were collected at 30 days and 1-year post-procedure.

Results:
A total of 32 patients were identified during this time period. 70.5 % were females, 96.8 % Caucasian. Mean NYHA class was 3.25, STS-PROM was 6.25% (5.56-9.43), and KCCQ score of 38.04 (SD 19.9). 94 % (30) of patients had a previous history of MV replacement and 6 % (2) of them had a history of MV repair. Baseline mean LVEF was 57% (46.5-67), at 30 days 55% (47.5-64.5) at 1 year 53.5% (46.5-58.25). NYHA decreased from 3.25 (1-4) to 2 (1-2) at 30 days and 2 (1.5-2) at 1 year with KCCQ following a similar trend. MV area at baseline was 1.2 (0.66-1.63) which increased to 1.45 (SD 0.44) at 30 days and 1.63 (SD 0.4) at 1 year. MV mean gradient decreased from 12.43 (SD 5.2) to 8 (7-10) at 30 days and remained stable at 9 (6-11) at 1 year. MR gradient decreased from severe MR in 11 patients (35.48 5 at baseline) to 6 (18.75 %) and 0 at 1 year. TR gradients followed the trend. The mortality rate at 30 days was 6.25 % (2) and 15.62% (5) at 1 year.

Conclusion:
TMVR offers acceptable outcomes in patients with symptomatic bioprosthetic mitral valve dysfunction. Follow-up data at 30 days and 1 year demonstrates improvement in functional status and sustained decrease in mitral valve gradients.
Abstract 14163: Mathematical Model for Predicting Survival in Elderly (Above 80 Years) Population After Primary Percutaneous Coronary Intervention for ST Elevation Myocardial Infarction
Authors: Saxena Aaruni , Jamil Copley Shahnaz , Jathanna Nikesh , Sprigg Nikola , Uddin Akhlaque
Published: April 2024

Introduction:
Advancement in interventional cardiology has increased the number of percutaneous coronary intervention (PCI) in the elderly. However, clinicians still face tough decision making to select elderly patients who can receive Primary PCI and have improved survival. This study aimed to identify factors that influence the survival in elderly population undergoing PPCI for treatment of ST elevation myocardial infraction (STEMI).

Methods:
We analyzed the data at our cardiac center prospectively during 2010- 2019 and developed a mathematical model using multi-parameter regression analysis using SPSS and OriginPro data visualization.

Results:
The factors which may predict survival were identified with help of mathematical model developed on the basis of clinical parameters reported at the time of STEMI presentation and details of the PCI procedure in 248 patients (male = 124, Age 85.78±3.43 years, , female= 124, Age 85.78± 4.08 years, ). The data visualization is shown in figure 1 and the developed model equation is as follows: Y (survival in months) = 126.865 - 0.258 (± 0.030) (Hb in g/dl) - 0.105(± 0.034) (Creatinine in umol/L) - 0.228 (± 0.112) (eGFR in ml/min/1.73 m
2
) - 4.174 (±2.443) (triglycerides in mmol/l) - 1.201 (± 1.232) (LDL in mmol/l) - 0.001(±0.002) (Call to balloon time in minutes) + 16.874 (±3.119) (log
10
radiation dose)- 1.224(±0.352) Age at time of presentation) (N = 248, R = 0.636, F= 18.043, p = 0.00)

Conclusions:
Our study shows that hemoglobin, kidney function, lipid profile, call to balloon time, age of the patient at time of STEMI presentation and radiation dose used during the procedure may be important predictors for the survival of patient after PPCI. Nevertheless the patient age at the time of STEMI is negatively correlated with survival period. Similarly, early intervention in event of STEMI will decrease call to balloon time thereby increasing post-procedure survival in elderly patients
.
Abstract 14181: Subclinical Left Ventricular Dysfunction in COVID-19 Recovered Patients Using Speckle Tracking Echocardiography
Authors: Kunal Shekhar , Mahajan Sudhanshu , Shah Bhushan , Girish MP , BANSAL ANKIT , Batra Vishal , Yusuf Jamal , Mukhopadhyay Saibal , Gupta Anubha , Gupta Mohit
Published: April 2024

Introduction:
Myocardial injury during active coronavirus disease-2019 (COVID-19) infection is well described however, its persistence during recovery is unclear. We assessed left ventricle (LV) global longitudinal strain (GLS) using speckle tracking echocardiography (STE) in COVID-19 recovered patients and studied its correlation with various parameters.

Methods:
A total of 134 subjects within 30-45 days post recovery from COVID-19 infection and normal LV ejection fraction were enrolled. Routine blood investigations, inflammatory markers (on admission) and comprehensive echocardiography including STE were done for all subjects.

Results:
Of the 134 subjects, 121 (90.3%) were symptomatic during COVID-19 illness and were categorized into mild: 61 (45.5%), moderate: 50 (37.3%) and severe: 10 (7.5%) COVID-19 illness groups. Asymptomatic COVID-19 infection was reported in 13 (9.7%) patients. Subclinical LV and right ventricle (RV) dysfunction were seen in 40 (29.9%) and 14 (10.5%) patients respectively. Impaired LVGLS was reported in 1 (7.7%), 8 (13.1%), 22 (44%) and 9 (90%) subjects with asymptomatic, mild, moderate and severe disease respectively. LVGLS was significantly lower in patients recovered from severe illness (mild: -21 ± 3.4%; moderate: -18.1 ± 6.9%; severe: -15.5 ± 3.1%; P < 0.0001). Subjects with reduced LVGLS had significantly high interleukin-6 (P < 0.0001), C-reactive protein (P = 0.001), lactate dehydrogenase (P = 0.009) and serum ferritin (P = 0.03) levels during index admission.

Conclusions:
Subclinical LV dysfunction was seen in nearly a third of recovered COVID-19 patients while 10.5% had RV dysfunction. Our study suggests a need of close follow-up among COVID-19 recovered subjects to elucidate long-term cardiovascular outcomes.
Abstract 14205: Myocarditis After COVID-19 Vaccination
Authors: Echeverry Tatiana , Norris Matthew , Weber Vance
Published: April 2024

As of 6/2021, over 165 million Americans have received at least one dose of the COVID-19 vaccine. Two of the major COVID-19 vaccines administered in the United States utilize mRNA technology. With the novel vaccine being administered to millions, rarer adverse effects are more likely to be identified. The following case highlights a young male patient with myocarditis in the days after mRNA COVID-19 vaccination.

Case presentation:
Patient is a 31-year-old male with no past medical history who presented with burning chest pain for two days after receiving his second [MN1] mRNA COVID-19 vaccine. The pain was associated with orthopnea and paroxysmal nocturnal dyspnea. Initial EKG showed no acute ischemic changes. [MN2] Blood work revealed elevated troponin of 1.7 and negative CRP and ESR. [MN3] Transthoracic echocardiogram revealed an ejection fraction of 55% with no wall motion abnormalities. The following day patient had CMR that showed an area of myocardial hyper-enhancement in the apical anterior segment suggesting the diagnosis of myocarditis. Patient was discharged with Metoprolol and was instructed to refrain from strenuous exercise. Patient was seen outpatient, and endorses to still experience intermittent burning substernal chest pain.

Discussion:
In the past few months, myocarditis and myopericarditis have been increasingly reported in CDC and case series following mRNA vaccination. A case review in
Pediatrics
outlines seven cases in healthy 14- to 19-year-olds who developed symptoms within four days of receiving their second dose. A large Israeli study reported 275 cases of myocarditis over the span of five months. These cases seem to be mild in character and tend to resolve within a week of onset. The connection between the mRNA vaccines and these cases has yet to be confirmed and remains under investigation by the CDC. We present this case in support of the growing literature, as recognition of the relationship between myocarditis and mRNA COVID-19 vaccines will allow these patients presenting with chest pain to receive higher value care while hopefully sparing them from receiving unnecessary invasive cardiac procedures.
Abstract 14223: Unfavorable Recent Trends in Smoking in Brazil - A Call for Innovation?
Authors: Depaivafagundes Ju Antonio , Malta Deborah , Brant Luisa , Teixeira Renato , Polanczyk Carisi A , Maria Moraes de Oliveira Glaucia , Ribeiro Antonio L
Published: April 2024

Introduction:
Tobacco use is one of the leading preventable causes of death in Brazil and worldwide. In addition, tobacco consumption through different forms of smoking is associated with an increased risk of cardiovascular events.

Objectives:
We analyzed the prevalence of smoking among adults in Brazil, and cardiovascular mortality rates attributable to tobacco, from 1990 to 2019

Methods:
The prevalence of current smokers was estimated using data from a cross-sectional, nationally representative survey (National Health Survey) and the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) from 2006 to 2019. Age-standardized mortality rates and the absolute number of deaths attributable to tobacco were obtained from the Global Burden of Diseases 2019.

Results:
The results indicate that 12.8% (95% CI, 12.4-13.2%) of adults use some tobacco product, being the use higher in males (16.2%; 95% CI, 15.6-16.9%) than in females (9.9%; 95% CI, 9.3-10.3%). The proportion of people over 18 years of age who smoke in 2019 was 12.6% (95% CI, 12.2-13.0%), 15.9% (95% CI, 15.3-16.6%) in males, and 9.6% (95% CI, 9.2-10.1%) in females, showing a significant decrease in the last three decades (34.8% in 1989). However, there was an increase of 0.5% in the prevalence compared to 2018, suggesting a change in the trends. In 2019, smoking was responsible for 65,693 deaths from cardiovascular disease in Brazil (39% of all deaths attributed to tobacco). Cardiovascular mortality attributable to smoking decreased from 88.0/100,000 inhabitants (95%UI, 81.3-94.3) in 1990 to 26.3/100,000 inhabitants (95% UI, 23.8-28.9) in 2019.

Conclusions:
The prevalence of tobacco consumption and cardiovascular mortality attributed to tobacco has decreased in Brazil in the past three decades. However, recent opposite trends call for attention, demanding innovation in addressing the prevention and reduction of smoking in Brazil.
Abstract 14229: Carcinoid Heart Disease: What Do We Know About Characteristics and Outcomes of Tricuspid Valve Replacement? A Nationwide Analysis
Authors: Bansal Agam , Gad Mohamed , Cremer Paul , Jaber Wael A , Menon Venu , wassif heba
Published: April 2024

Introduction:
In patients with severe tricuspid and pulmonary valve regurgitation and symptoms of heart failure secondary to carcinoid heart disease, valve replacement is the only effective treatment and can improve survival. Previous data on outcomes of valve replacement in carcinoid heart disease have been limited to case reports or single-centre study. Therefore we aimed to perform a nationwide database to ascertain the outcomes of tricuspid valve replacement (TVR) in carcinoid heart disease.

Methodology:
We utilized nationwide readmission database (NRD) to identify hospitalizations for tricuspid valve replacement in 2018. Hospitalizations with valve replacement for infective endocarditis were excluded. Characteristics and outcomes were compared between patients undergoing TVR for carcinoid versus other reasons. Multivariable logistic regression was performed to examine the predictors of in-hospital mortality after TVR.

Results:
A total of 1192 hospitalizations for TVR were included in the analysis of which 57 had carcinoid heart disease. There were no significant differences in short-term outcomes including in-hospital mortality (12.6% vs 11.5%, p=0.839), acute renal failure, blood transfusion, cardiogenic shock, new pacemaker insertion, length of stay and 30-day readmissions between TVR for carcinoid vs other etiologies (Table). The independent predictors of mortality in patients undergoing TVR were advanced liver disease (4.67 (2.59-8.43), p<0.001), end stage renal disease (5.09 (2.10-12.01), p<0.001), acute heart failure (2.00 (1.10-3.67), p=0.022), malnutrition (2.24 (1.13-4.31), p=0.017), and age (1.02 (1.01-1.04), p=0.020), whereas carcinoid heart disease was not an independent predictor of mortality (aOR: 1.52 (0.39-4.65), p=0.497).

Conclusion:
Tricuspid valve replacement in patients with carcinoid heart disease is associated with comparable short-term outcomes as for other etiologies.
Abstract 14301: Investigation of an Injection-Jet Self-Powered Fontan Circulation
Authors: Prather Ray , Das Arka , Farias Michael , DIVO Eduardo , Kassab Alain J , Decampli William M
Published: April 2024

Introduction:
The Fontan circulation is a fragile system in which imperfections at any one of multiple levels may compromise quality of life. Increased inferior vena caval (IVC) pressure itself may play some role in “Fontan failure”. The Fontan circulation is powered with a high speed injection jet shunt (IJS) drawing flow from the aortic arch, balanced by a fenestration to preserve the ratio of pulmonary flow (Qp) to systemic flow (Qs). The high-velocity jet causes flow entrainment, leading to a significant reduction of upstream pressure. We describe a tightly coupled multi-scale lumped parameter/computational fluids dynamics (LPM-CFD) model to validate this hypothesis.

Methods:
A synthetic 3D CAD model of the fenestrated total cavopulmonary connection (TCPC) was generated, with average dimensions matching those of a 2-4 yo patient. The prescribed cardiac output is of about 2.3L/min. The detailed 3D pulsatile hemodynamics in the fluid domain are modeled as unsteady, turbulent and incompressible. Blood is assumed to be non-Newtonian. Turbulence is approximated using a large eddy simulation (LES) approach. Potential optimal IJS configurations were determined by with a parametric sweep of several geometric design parameters such as TCPC morphology, shunt diameter and location, and fenestration diameter and location. The effects of the IJS implementation on IVC pressure with a fenestration and systemic oxygen saturation were calculated using a tightly coupled LPM-CFD.

Results and Discussion:
A set of baseline simulations representing a failing Fontan, with elevated IVC pressure (+17.8mmHg). Enlargement of the fenestration to 7 mm results in a 3 mm Hg IVC pressure drop but also significant reduction in systemic oxygen saturation (assuming a 96% pulmonary venous O2 saturation level). Addition of an IJS (2mm nozzle) to this model preserves the IVC pressure drop of 3.2mmHg but improves systemic oxygen saturation with only a small additional volume load to the ventricle (CO/Qs = 1.2).

Conclusions:
This study demonstrates the potential salutary effect of the IJS on the Fontan circulation. Further exploration of adjustable anatomic and parameters are needed to further reduce IVC pressure and improve systemic saturation.
Abstract 14334: Significance of Bariatric Surgery on Mortality and Heart Failure Readmissions Among Patients With Heart Failure and Preserved Ejection Fraction
Authors: Thakkar Samarthkumar J , Patel Harsh P , Sheth Aakash , Chowdhury Medhat , Kansara Tikal , Munshi Rezwan , Patel Smit , Baibhav Bipul , Gandhi Alok , Feitell Scott , Parikh Vishal
Published: April 2024

Introduction:
The role of bariatric surgery in patients with heart failure with preserved ejection fraction (HFpEF) is debatable.

Hypothesis:
Bariatric surgery in patients with HFpEF is associated with a reduction in mortality and HF readmissions at 1 year.

Methods:
Patients with HFpEF who underwent bariatric surgery were identified by analyzing the nationwide readmission database and incorporating the validated ICD-10 CM codes. We performed the propensity score matching to adjust for the confounders and cox proportional hazard regression to generate hazard ratios. Moreover, we generated Kaplan Meier curves for time to event analysis. All-cause mortality at 1 year was the primary outcome whereas, heart failure readmission and readmission due to any other cause at 1 year were the secondary outcomes.

Results:
Out of 338939 patients with HFpEF, 2214 underwent bariatric surgery. After propensity score matching, 2209 patients were identified with bariatric surgery and 2271 without. At 1 year, bariatric surgery failed to show a significant reduction in mortality (5.22% vs. 6.81%, HR: 0.97, 95% CI: 0.73-1.31, p=0.88). Additionally, there was no difference in HF admissions (16.80% vs. 19.03%, HR: 0.94, 95% CI: 0.81-1.09, p=0.44) as well as any readmissions (50.20% vs. 49.34%, HR: 0.94, 95% CI: 0.86-1.03, p=0.19) at 1 year between both the groups.

Conclusions:
Bariatric surgery in patients with HFpEF failed to show a reduction in mortality, HF readmission, and readmission due to any cause at 1 year. Further studies are needed looking at a larger sample size, more long-term data, and functional status/quality of life.
Abstract 14366: Pulmonary Hypertension-Induced RV Hypertrophy and Dysfunction is Associated With Reduced Activity and Abundance of Complex IV in Respiratory Supercomplexes
Authors: Ma Wenzhuo , Vang Alexander , Huck Scarlett , Mancini Thomas , Nicely Preston , Zhang Peng , Choudhary Gaurav , Clements Richard T
Published: April 2024

Introduction:
PH results in RV hypertrophy, fibrosis and impaired function resulting in RV failure. PH is associated with impaired heart metabolism and mitochondrial respiration. Mitochondrial supercomplexes (mSC) are assemblies of multiple electron transport chain (ETC) complexes that consist of physically associated complex I, III and IV to enhance respiration. We determined if activity and/or abundance of mSC’s is altered in a rat model of PH.

Methods:
PH was induced in SD-rats by Sugen-Hypoxia (3 weeks) followed by normoxia (4 weeks) . Control (n=11) and PH (n=10) were subjected to echocardiography and isolation of LV and RV mitochondria. Clear native PAGE with equal amounts mitochondrial protein was used for SC abundance and activity with immunoblot or in gel activity with specific substrates.

Results:
PH animals had significantly reduced PAT and TAPSE, increased RV wall thickness and hypertrophy (RV/LVS). Western analysis of total protein fractions demonstrated reductions in representative CI, II, III, and IV proteins in RV indicating reduced mitochondrial content in PH. Assays with normalized mitochondrial protein showed activity (100+/- 3.6 vs 64.0+/-3.8 %, p<.01) and abundance (100+/-1.8 vs 49.3 +/-1.1, p=.02) of complex IV in mitochondrial SCs was severely reduced in PH animals compared to control. There were no differences in total CIV activity or abundance in lower order ETC assemblies (100 vs 97.5%, p=.78). TAPSE, PAT and RV Wall thickness significantly correlated with CIV SC activity (r=.71, .66, and -.80 respectively P<.01). CIII abundance was lower in SCs (P=.01) but total CIII unchanged. CI activity in SC assemblies was reduced in PH but this was not significant (100+/-12 vs 77.4 +/-8.2, p=.14). Overall levels of CI were unchanged. There were no changes in CII activity or abundance in RV or LV. In the LV, activity of CIV in SC was reduced in PH (100+/-6 vs 78+/-6, p=.02) but to a lesser extent than RV. There were also decreases in overall abundance of CIII and CIV assemblies in the LV in PH.

Conclusion:
The data support the concept that although mitochondrial abundance may be altered, there are also significant alterations associated with assembly and activity of mitochondrial SCs in the RV with pronounced differences in complex IV assembled into SCs.
Abstract 14368: Valproic Acid Activates Irg1-Itaconate and Improve Donor Heart Function After Extended Storage Time
Authors: Lei Ienglam , Huang Wei , Mortensen Richard , Wang Zhong , Chen Eugene , Tang Paul C
Published: April 2024

Background:
Cold ischemic storage and subsequent reperfusion injury contributes to the primary graft dysfunction after heart transplantation. Valproic acid (VPA) has been shown to reduce myocardial infarction injury. However, the role of VPA in donor heart preservation is unknown.

Methods:
We investigate the role of VPA on donor heart preservation using both ex-vivo perfusion and heterotopic transplantation in murine models.

Results:
Our results demonstrate the administration of VPA to histidine-tryptophan-ketoglutarate (HTK) cardioplegia can significantly improve donor heart function after perfusion with extend storage time (16 hours, n=8). Specifically, VPA reduced the accumulation of succinate, a metabolite that involved in reperfusion injury, during cold storage. We further show that VPA increases the Irg1 expression. Irg1 is known to produce itaconate and suppress the succinate accumulation during ischemia. We found that the effect of VPA in donor heart function is significantly reduced in Irg1 knockout mice compared to wild type mice after 16 hours of cold storage. Furthermore, VPA reduced oxidative stress of donor heart via Nrf2 antioxidant pathway activation. However, Irg1 deletion decreased the induction of antioxidant genes expression by VPA. Administration of 4-octyl-itaconate rescued donor heart function after extended storage.

Conclusion:
Our results demonstrate that VPA could improve donor heart function and ischemic tolerance. This is in part through Irg1/itaconate mediated anti-oxidative activities. Importantly, VPA preserved cardiac function after perfusion with extended storage times. This strategy can extend the tolerable ischemic time for donor heart for heart transplant and may reduce the incidence of primary graft dysfunction.
Abstract 14369: Smooth Muscle Specific Deletion of RSK2 Suppresses Vasoconstriction of Resistance Arteries
Authors: Ayon Ramon J , Kalara Jaspreet K , Sonkusare Swapnil K , Somlyo Avril V
Published: April 2024

Introduction:
Intracellular Ca
2+
is a vital second messenger that plays a fundamental role in regulating intraluminal pressure- and agonist-induced vasoconstriction. Our laboratory previously demonstrated that intraluminal pressure and G-protein coupled receptor agonist stimulation activate p90 ribosomal S6 kinase 2 (RSK2). RSK2, in turn, phosphorylates the regulatory light chain of myosin (RLC
20
) to induce constriction of small, resistance-sized arteries. More recently, we discovered that resistance arteries from global KO RSK2 mice exhibited a more dilated luminal diameter, reduced myogenic tone and RLC
20
phosphorylation, and decreased blood pressure. However, it is unclear whether the observed effects are a result of RSK2 global deletion in the mouse which may cause developmental abnormalities affecting the cardiovascular system.

Hypothesis:
We hypothesize that smooth muscle-specific RSK2 signaling in mouse resistance arteries is a significant regulator of myogenic tone and arterial stiffness.

Methods:
Inducible smooth muscle-specific KO mice for RSK2 (RSK2
SMC-/-
) were generated to study the role of RSK2 signaling in the regulation of vascular tone. Pressure myography studies assessed vascular reactivity in 4
th
- and 5
th
-order mesenteric arteries (MAs) isolated from RSK2
SMC-/-
and RSK2
fl/fl
mice.

Results:
The downregulation of normal RSK2 expression in resistance arteries was confirmed by Western blot. Our data shows that the intraluminal pressure-induced constriction of MAs is significantly attenuated in RSK2
SMC-/-
mice (n=7 each group). Additionally, RSK2
SMC-/-
resistance arteries experienced a delay in development of myogenic tone at 40 mmHg indicating that RSK2 signaling is sensitive to small changes in intraluminal pressure. Furthermore, MAs from RSK2
SMC-/-
mice exhibited decreased vascular stiffness (indicated by enhanced strain, and rightward shift of stress-strain relationship) when compared to MAs from RSK2
fl/fl
mice.

Conclusions:
This study provides novel evidence that smooth muscle RSK2 signaling contributes to pressure-induced vasoconstriction, and vascular stiffness. Inhibiting smooth muscle RSK2 activity may represent a novel strategy for rescuing vascular function in hypertensive patients.
Abstract 14372: The Acquired Long QT-Causing Drugs Haloperidol and Terfenadine Cause Defects in HERG Trafficking
Authors: McKernan Abagail , Mehdi Haider , Greiner Alexander , Yoon Jin-Young , Colgan Diana , Dierdorff Jason , London Barry
Published: April 2024

Background:
Mutations in K
v
11.1 (HERG) cause inherited long QT syndrome (LQTS) type 2 by disrupting channel function or membrane trafficking. Acquired LQTS is caused by drug binding to HERG and directly blocking the channel pore, reducing I
Kr
and prolonging QTc in persons with decreased repolarization reserve. Alternatively, these drugs could bind to HERG and interfere with trafficking, reducing the number of HERG channels at the membrane.

Objective:
We sought to understand the effects of known acquired LQTS-causing drugs from various classes (terfenadine, haloperidol, ondansetron, fluconazole, azithromycin) on HERG trafficking.

Methods:
HEK293 cells stably expressing HERG (HERG-HEK293) were cultured in varying concentrations of selected drugs for 24 hours. Differences in trafficking were identified by immunoblot using the terminally-glycosylated HERG at 155 kD and the immature core-glycosylated HERG at 135 kD. Both the mutant HERG-G601S and HERG-HEK293 cells treated for 24 hours with arsenic trioxide (As
2
O
3
) served as trafficking-deficient controls.

Results:
HERG-HEK293 cells treated with haloperidol (
>
50 μM) demonstrated a decrease in the size of the terminally glycosylated band, appearing at 140-145 kD in comparison to the fully glycosylated 155 kD (Fig. 1A). HERG-HEK293 cells treated with terfenadine (
>
15 μM) demonstrated a deficiency in terminal glycosylation (Fig. 1B). Ondansetron, fluconazole, and azithromycin treatments at 1, 10, and 100 μM demonstrated no effect on the fully glycosylated band.

Conclusions:
These data suggest terfenadine and haloperidol interfere with HERG trafficking, resulting in less mature HERG at the membrane. Together, these data provide insight into a non-pore blocking mechanism that may underlie some cases of acquired LQTS.
Abstract 14382: Association of Atherosclerotic Plaque Burden and FFR
CT-
Serial Cardiac CTA Study
Authors: Shaikh Kashif , Kinninger April , Dahal Suraj , Lakshmanan Suvasini , Golub Ilana , ALLA VENKATA M , Leipsic Jonathon , Budoff Matthew
Published: April 2024

Introduction:
Cross-sectional studies have shown the association of atherosclerotic plaque burden and FFR
CT
. However, the relationship between changes in anatomic CCTA parameters and FFR
CT
has not been evaluated. In the present study, we sought to study the natural history of FFR
CT
and to observe the impact of coronary plaque characteristics on intracoronary hemodynamics over time as assessed by noninvasive CCTA.

Methods:
Patients who had undergone baseline and follow-up CCTA were included. Coronary plaque scores and vessel stenosis severity were quantified on CCTA. Multivariate linear regression was used to examine the association of change in the per vessel FFR
CT
, average distal FFR
CT,
and the most diseased vessel FFR
CT
with total plaque score(TPS), coronary artery calcium(CAC), total segment stenosis (TSS), segment involvement score (SIS).

Results:
Final analysis included 101 subjects (83% male; age 65.5 ± 10.1 years). After adjusting for several cardiovascular risk factors, on a per-vessel basis involving the most significant lesion, a 1 unit increase in TPS resulted on average in a 0.008 decrease in FFR in the most diseased vessel, p=0.004, after adjusting for several risk factors. Using the average FFR
CT
of the distal LAD, RCA, and LCX, a 1 unit increase in TPS results on average in a 0.004 decrease in the distal average FFR, p=0.026. A 1 unit increase in TPS results on average in 0.005 decrease in the RCA distal pins of FFR, p=0.033 (Table 1). There are no significant associations of the LCX and LAD FFR with TPS. There are no significant associations of the change in FFR
CT
with TSS, SIS or CAC progression.

Conclusion:
Worsening atherosclerotic plaque burden is associated with worsening physiology as assessed on CCTA as assessed by FFR
CT
. Therapies that stabilize or regress plaque may improve overall physiology. Further prospective trials are required to validate these findings.
Abstract 14400: Prevalence of Arrhythmias and Conduction Disease in Patients Hospitalised With Cardiac Amyloidosis
Authors: Yalamanchili Sreeram , Atluri Ramtej , Vallabhaneni Meghana , Kodali Mouna , Krishan Satyam
Published: April 2024

Introduction:
Cardiac Amyloidosis (CA) is an infiltrative cardiomyopathy that results in deposition of misfolded amyloid fibrils into the myocardium, and is thought to disrupt the conduction system. As there is limited data regarding the prevalence of arrhythmias and conduction disease in patients with cardiac amyloidosis, we sought to determine their prevalence in patients hospitalized with CA using the National Inpatient Sample (NIS) from 2017.

Methods:
A retrospective study was done using the Nationwide Inpatient Sample from 2017. 18,380 patients with cardiac amyloidosis were identified using ICD-10 codes. Multivariate logistic regression analysis was used to adjust for confounders and analyze the variables for the adjusted odds ratio.

Results:
Among 18,380 total patients, the average age was 74 and 56% were male. Atrial fibrillation (AF) was the most prevalent (34%) atrial arrhythmia followed by atrial flutter (AFL) (5.2%) and supraventricular tachycardia (SVT) (3.0%). Ventricular tachycardia (VT) was the most common ventricular arrhythmia (4.9%) and less than one percent of the cohort had reported episodes of ventricular fibrillation/flutter (< 1%). In terms of conduction disease, 3.5% had either first-degree (1AVB) or second-degree AV block (2AVB), and 3.2% had either right (RBBB) or left bundle branch block(LBBB). When adjusted to patient demographics, comorbidities, and hospital characteristics, patients with CA had higher risk of AF (aOR= 1.69, p<0.0001), AFL (aOR=2.3, p<0.0001), SVT (aOR=1.78, p<0.0001), VT (aOR=2.3, p<0.0001), ICD (aOR=1.5, p <0.0001), RBBB (aOR=1.32, p=0.048), 1AVB (aOR=1.82, p<0.0001), and 2AVB (aOR=2.24, p<0.0001) as compared to those without.

Conclusions:
Patients with cardiac amyloidosis are more likely to develop atrial fibrillation, atrial flutter, supraventricular tachycardia, ventricular tachycardia, RBBB, 1AVB, and 2AVB. Atrial fibrillation was the most common arrhythmia found in our cohort, and this is consistent with trends seen in prior observational studies.
Abstract 14405: Impact of Educational Attainment on All-Cause and Cardiovascular Mortality: Findings From a National Study of US Adults
Authors: Khan Najah , Javed Zulqarnain , Acquah Isaac , Khan Madiha , Taha Mohamad , Hagan Kobina , Khan Safi U , Chang Ryan , Elizondo Javier , Cainzos-Achirica Miguel , Nasir Khurram
Published: April 2024

Introduction:
Education is an important determinant of cardiovascular disease (CVD). However, the extent to which educational attainment impacts the risk of all-cause and cardiovascular (CV) mortality on a population level is relatively understudied.

Methods:
We used data from 2006-2014 National Death Index-linked National Health Interview Survey for adults ≥ 18 years. We generated age-adjusted mortality rates (AAMR) by levels of education (< High School (HS), HS/General Education Development (GED), Some College, and > College) in adults with and without CVD. Cox proportional hazards models were used to examine the association between educational attainment and all-cause and CV mortality.

Results:
Final sample comprised of 256,991 participants (mean age=46.3), representing ~230 million adults annually, of which 8% had ASCVD. Overall, 14.8% of participants had  College education, respectively. During a median follow-up of 4.5 (IQR: 2.5-6.8) years (1179 million person-years), all-cause and CV AAMRs were approximately 1.5 and 2 fold higher, respectively, for College education in the CVD population and 2 fold higher in the non-CVD population (
Figure 1
). In fully adjusted models, < HS (reference= >College) was associated with 20% increased risk of all-cause (HR 1.20, 95% CI: 1.07-1.35) and 40% increased risk of CV mortality (HR 1.41, 95% CI: 1.10-1.81) in the CVD population, compared to 40-45% increased risk of mortality in the non-CVD population (all-cause mortality HR 1.39, 95% CI: 1.29-1.49; CV mortality HR 1.45, 95% CI: 1.20-1.75). Similar trends were seen by race/ethnicity (data not shown).

Conclusions:
Lower education is an independent predictor of all-cause and CV mortality in both CVD and non-CVD populations. Efforts for integration of educational attainment into existing CV risk prediction algorithms are needed to mitigate observed socioeconomic disparities in mortality.
Abstract 14412: Endothelial Cell-Selective Adhesion Molecule Deficiency in Mice Causes Vascular Endothelial Dysfunction and Impairs Left Ventricle Diastolic Function
Authors: Buncha Vadym , Fopiano Katie , Tian Yanna , Lang Liwei , Bagi Zsolt A
Published: April 2024

Dysfunction of vascular endothelium plays a key role in the development of left ventricular diastolic dysfunction (LVDD) in patients with heart failure with preserved left ventricular ejection fraction (HFpEF). Recently, Endothelial Cell-Selective Adhesion Molecule (ESAM) was proposed as a novel biomarker in HFpEF. We hypothesized that ESAM plays a mechanistic role in the development of both microvascular dysfunction and LVDD. ESAM knockout and wild type (WT) mice were employed. Using transthoracic echocardiography it was found that ESAM knockout mice displayed LV diastolic dysfunction, as indicated by a significantly reduced E/A ratio (E=early, A=late mitral inflow peak velocities), increased E/e’ ratio, isovolumic relaxation time (IVRT) and increased E wave deceleration time, with no change in the ejection fraction. The systolic blood pressure, as measured by tail-cuff plethysmography, was not different between ESAM knockout and WT mice; and no cardiac hypertrophy was detected in the ESAM knockout mice. Vasodilator function of the pulmonary artery and aorta was assessed using wire myography. We found that the endothelium-dependent, acetylcholine-induced relaxation of the aorta and pulmonary artery was significantly reduced in ESAM knockout mice, whereas endothelium-independent, nitric oxide donor, sodium nitroprusside-induced relaxation was similar in the two groups. Thus, we concluded that ESAM deficiency in mice display a HFpEF phenotype, in that ESAM knockout mice develop endothelial dysfunction and LVDD.
Abstract 14413: Genetic Deletion of Cardiomyocyte Glutamine Synthetase in a Model of HF Hints at Cardiomyocyte to Fibroblast Metabolic Crosstalk Mediating Fibrosis
Authors: Gibb Andrew A , Ploesch Tori , Arany Zoltan , Elrod John W
Published: April 2024

Introduction:
Recent evidence in heart failure patients revealed a significant release of glutamine from the heart as evidenced by arterial-coronary sinus concentration differences. Interestingly, enhanced glutamine utilization is required for fibroblast to myofibroblast differentiation and persistence in response to stress stimuli. Therefore, the aim of this study was to determine if cardiomyocyte-derived glutamine influences fibroblast activation and fibrosis.

Methods:
To determine the effects of cardiomyocyte glutamine production in the failing heart, glutamine synthetase floxed mice (GS
fl/fl
) were bred with the cardiomyocyte-specific, tamoxifen-activated Cre mice (MCM).
(GS catalyzes the condensation of glutamate to glutamine.) GS
fl/fl
x MCM and MCM controls were fed tamoxifen chow for 1w followed by a 1w washout. Western blotting confirmed cardiomyocyte GS deletion and baseline LV function was assessed by echocardiography, followed by randomization to sham or TAC surgery. Cardiac function was tracked at 4, 8, and 12wks post-TAC followed by tissue collection, assessment of gravimetrics, and histological staining.

Results:
Cardiomyocytes isolated from
GS
fl/fl
x MCM hearts following tamoxifen administration revealed a near complete loss of GS protein. While loss of GS did not impact baseline cardiac function,
GS
fl/fl
x MCM mice were significantly protected against pressure-overload induced cardiac dysfunction indicated by preserved FS% (n=8/group; p<0.0001) and decreased LVESD (n=8/group; p=0.001). Deletion of cardiomyocyte GS did not appreciably impact hypertrophy. To ascertain if the fibrotic response was altered, we performed picrosirius red staining 12w following TAC. Hearts from
GS
fl/fl
x MCM mice showed an ~3-fold reduction in total cardiac fibrosis, as compared to MCM controls. (n=6/group; p=0.01).

Conclusions:
Our results suggest that cardiomyocyte glutamine synthesis may play a significant role in fibroblast activation and fibrosis in heart failure. Studies are currently underway to identify the precise mechanisms governing metabolic cardiomyocyte to fibroblast crosstalk.
Abstract 14441: Anemia is Associated With Coronary Microvascular Dysfunction and Future Adverse Outcomes in Patients With Non-Obstructive Coronary Artery Disease
Authors: Ozcan Ilke , Ahmad Ali , Toya Takumi , Sara Jaskanwal D , Corban Michel , Rajai Nazanin , Lerman Lilach , Lerman Amir
Published: April 2024

Introduction:
Coronary microvascular dysfunction (CMD) is associated with increased morbidity and mortality. Anemia is an important predictor of outcomes in several cardiovascular diseases, such as heart failure and coronary artery disease (CAD), however its significance in patients with non-obstructive CAD is not fully elucidated.

Hypothesis:
We hypothesized that anemia would be associated with CMD and future adverse outcomes.

Methods:
We enrolled 1334 patients with signs and/or symptoms of ischemia and with non-obstructive CAD (<50% angiographic stenosis) who underwent invasive CMD evaluation and had follow-up data. CMD was defined as coronary flow reserve (CFR) (hyperemic flow/baseline flow as measured by the doppler wire) of ≤2 in response to intracoronary adenosine injection. Anemia was defined as a Hgb < 13.0 g/L in males and <12.0 g/L in females. MACE was defined as any incidence of myocardial infarction, cardiac revascularization (PCI, CABG) and all-cause mortality.

Results:
Overall mean age was 51.3±12.4 years, 66% were female. Patients with anemia were more likely to be female and have diabetes mellitus. Anemics were more likely to be diagnosed with CMD (Odds Ratio 2.01, 95% Confidence Interval [1.14-3.54]; P = 0.02). This relationship remained significant even after adjusting for cardiovascular risk factors like age, sex, hypertension, diabetes mellitus and dyslipidemia (OR 1.84, 95% CI [1.03-3.29], P = 0.04). Furthermore, patients with anemia were more likely to experience MACE (OR 1.86, 95% CI [1.30-2.66], P = 0.001), independent of possible confounders (OR 1.84, 95% CI [1.27-2.69], P = 0.002).

Conclusions:
Anemia is an independent predictor of CMD and future adverse cardiovascular events in patients with NOCAD. Moreover, it was associated with an increased risk of future adverse events. Further studies are needed to elucidate whether treatment of anemia in this population translates into outcomes.
Abstract 14455: Outcomes and Revascularization Strategies for ST Elevation Myocardial Infarction in Patients With Hypertrophic Cardiomyopathy
Authors: Ariss Robert W , Minhas Abdul , NAZIR SALIK , Cash Ayla , Denktas Ali E , Jneid Hani
Published: April 2024

Introduction:
Myocardial ischemia is a well-known complication of hypertrophic cardiomyopathy (HCM). There are limited contemporary data on outcomes and revascularization strategies of STEMI outcomes in HCM.

Methods:
The National Inpatient Sample 2004-2018 was queried to identify adult patients presenting with a primary diagnosis of STEMI. Patients with STEMI and a concomitant diagnosis of HCM were subsequently identified. Complex samples multivariable logistic and linear regression models were used to determine the association of HCM with in-hospital outcomes (all-cause mortality, invasive mechanical ventilation, cardiogenic shock, mechanical circulatory support, and cardiac arrest). Outcomes of HCM patients with STEMI who were revascularized were also compared with their counterparts who were not revascularized.

Results:
Of 3,049,068 primary STEMI hospitalizations included within this study, 2,583 (0.8%) had an associated diagnosis of HCM. HCM patients were more likely to be elderly and female with less traditional cardiovascular risk factors compared to those without HCM. HCM patients were also less likely to receive percutaneous coronary intervention compared to those without HCM (42.8% 66.3% vs. P<0.001). STEMI with HCM was associated with similar in-hospital mortality (adjusted odds ratio [aOR] 1.09; 95% confidence interval [CI] 0.82-1.44; P=0.561) and other outcomes compared to those without HCM
(Table 1)
. Notably, STEMI patients with HCM who were revascularized had similar in-hospital mortality (aOR 0.69; 95% CI 0.36-1.33; P=0.266) compared to their HCM counterparts who did not receive revascularization.

Conclusions:
Despite lower rates of revascularization, STEMI with HCM is associated with similar in-hospital mortality compared to those without HCM.
Abstract 14496: The Role of ACE Inhibitors and Angiotensin Receptor Blockers in Cryoballoon Ablation Outcomes for Paroxysmal Atrial Fibrillation
Authors: Al-seykal Ibragim , Bose Abhishek , Chevli Parag A , Mishra Ajay K , Hashmath Zeba , Berberian Gregory , Januszkiewicz Jerzy , Dai Qiying , Laidlaw Douglas
Published: April 2024

Background:
Cryoballoon ablation (CBA) is recommended for patients with paroxysmal atrial fibrillation (AF) refractory to anti-arrhythmic drugs. However, only 70% of patients benefit from an initial CBA. There is a growing evidence that pretreatment with angiotensin converting enzyme inhibitors (ACE-I) and angiotensin receptor blocker (ARB) decreases recurrence of AF post ablation, particularly in non-paroxysmal AF undergoing radiofrequency ablation. The role of ACE-I and ARB in patients with paroxysmal AF in CBA remains unknown. We decided to investigate the role of ACE-I and ARB in preventing recurrence of atrial arrhythmias (AA) following CBA for paroxysmal AF.

Methods:
We followed 103 patients (Age 60.6 ± 9.1, 29% women) with paroxysmal AF undergoing CBA for one year post procedure. Recurrence was assessed by documented AA on EKG or any form of long-term cardiac rhythm monitoring. A multivariable cox proportional hazard model was used to assess if ACE-I or ARB treatment predicted risk of AA recurrence.

Results:
After a one year follow up, 19 (18.4%) participants developed recurrence of AA. Use of ACE-I or ARB therapy was noted in the study population. Patients on ACE-I/ARB had a greater prevalence of hypertension and coronary artery disease. On a multivariate model adjusted for baseline demographics and risk factors for AF, ACEI or ARB therapy did not prevent recurrence of AA following CBA (Table, p=0.72). Similarly, on Kaplan-Meier analysis pretreatment with ACE-I/ARB did not predict time to first recurrence of AA (Figure, p=0.2173).

Conclusion:
In our study population pre-ablation treatment with an ACE-I or an ARB had no influence on the recurrence of AA following CBA for paroxysmal AF.
Abstract 6905: Implementing, Launching and Sustaining a Quality Improvement Initiative in the Era of COVID-19: Challenges and Successes
Authors: Xiang Kun , McManus David , Catalano Christina , Ash Sue , Fry Patrick , Morales Jose , Becoats kyeesha , Mikulic Sebastian , Martinez Andres , Rivas Jose , Smith Anne Marie , Martin Lowe Mary , Araia Almaz , Kapoor Alok , Catanzaro John N
Published: April 2024

Introduction:
Only 60% of atrial fibrillation (AF) patients with elevated stroke risk receive anticoagulation (AC). Closing this gap in AC use is particularly challenging in the face of the COVID-19 pandemic. Electronic health record (EHR) alerts integrated into in-person and telehealth visits have the potential to close the gap.

Hypothesis:
A triad approach consisting of interventions at the practice provider at patient level could improve anticoagulation rates in patients with atrial fibrillation.

Methods:
In collaboration with the Heart Rhythm Society Quality Improvement Committee and UMass, University of Florida (UFL) Jacksonville launched a 2020 quality improvement (QI) intervention, including several Plan-Do-Study-Act (PDSA) cycles, centered around an outpatient, electronic health record (EHR) alert linked to an order set for AC meds, labs, and specialty referrals. The alert fired when cardiologists or primary care physicians saw AF patients in clinic with a CHA
2
DS
2
-VASc score of ≥2 who were not on AC. Due to COVID-19, several of the PDSA interventions required adjustments due to redeployment of information technology staff mobilized to generate COVID-19 reports, a pivot for clinicians and patients to telehealth visits, and a change in clinician and patient priorities from routine cardiovascular/preventive care to COVID-19 diagnosis and prevention. To assess intervention effectiveness, the change in AC use as a function of time was measured using a weighted least squares linear regression.

Results:
At time of launch, 2357 of 3555 eligible patients (56.3%) were on AC. At study end, six months later, the percentage of patients on AC increased by 1.5% to 57.8 %. Based on the population of untreated patients at UFL and the stroke rate for untreated patients (available from large registry data), and assuming absence of any competing/secular trend to explain the growth in AC use, we calculated that a 1.5% increase in the AC treatment percentage could result in the prevention of 1.5 strokes over one year.

Conclusion:
We demonstrated that an EHR alert can raise the rate of AC use in patients with AF after several rounds of PDSAs. In future efforts, we plan to reassess the AC percentage in our population and confirm the sustainability of our QI efforts as attention focuses back from the pandemic to routine cardiovascular/ preventive care.