bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 11959: The Relationship of Matrix Gla Protein With Coronary and Extracoronary Calcification in the Multi-Ethnic Study of Atherosclerosis
Authors: Berlot Ashley A , Fu Xueyan , Shea Kyla , Tracy Russell , Budoff Matthew J , Kim Ryung , Naveed Mahim , Booth Sarah , Kizer Jorge R , Bortnick Anna E
Published: December 2023

Introduction:
Vascular calcification regulators are understudied. Matrix Gla protein (MGP) is a calcification inhibitor, and its inactive dephosphorylated-uncarboxylated (dp-ucMGP) form has been linked to calcification. The longitudinal relationship of dp-ucMGP with coronary and extracoronary artery calcification in large populations is unknown.

Hypothesis:
Higher levels of dp-ucMGP may be associated with greater coronary artery, ascending thoracic aortic, and descending thoracic aortic calcification (CAC, ATAC, DTAC).

Aim:
To determine the association of dp-ucMGP with CAC, ATAC, and DTAC.

Methods:
Calcification was measured on serial thoracic computed tomography (CT) scans in the Multi-Ethnic Study of Atherosclerosis (MESA, n=6814). Dp-ucMGP was measured at baseline in a random subset of available serum samples (n=2663), 2539 included in the fully adjusted models) in participants with a baseline (2000-02) and follow-up CTs at Exam 5 (2010-12) (
InaKtif MGP
ELISA, Perkin Elmer, Waltham, MA). Linear mixed effect models were used to determine the association of baseline dp-uc MGP levels with long-term CAC, ATAC, and DTAC incidence and progression.

Results:
Participants were on average 61
+
9 years, 51.3% women, and 37.7% white. For each one standard deviation (178 pmol/L) increase in dp-ucMGP, CAC increased by 3.44 ([95% CI = 1.68, 5.21], p<0.001) Agatston units/year (AU/year), ATAC increased by 0.63 ([95% CI = 0.27, 0.98], p=0.001) AU/year, and DTAC increased by 8.61 ([95% CI = 4.55, 12.67], p<0.001) AU/year, in fully adjusted models.

Conclusion:
We found an association of the inactive form of matrix Gla protein, dp-ucMGP, with long-term incidence/progression of CAC, ATAC, and DTAC. Future studies should investigate MGP as a calcification regulator and possible therapeutic target.
Abstract 12042: Elevated Levels of Bicarbonate Predict Adverse Outcomes in Patients With Chronic Heart Failure
Authors: Misaka Tomofumi , Sato Yu , Sugawara Yukiko , Ogawara Ryo , Ichimura Shohei , Tomita Yusuke , Anzai Fumiya , Yokokawa Tetsuro , Sato Akihiko , Shimizu Takeshi , Sato Takamasa , Oikawa Masayoshi , Kobayashi Atsushi , Yoshihisa Akiomi , Takeishi Yasuchika
Published: December 2023

Background:
The bicarbonate (HCO3
-
) buffer system plays a crucial role in maintaining acid-base homeostasis, and HCO3
-
levels are affected by multiple factors in heart failure. Recently, a sub-analysis of the ADVOR trial for acute heart failure revealed that patients with elevated serum HCO3
-
levels experienced beneficial effects of decongestion by acetazolamide. However, the significance of HCO3
-
levels in chronic heart failure has not been fully understood.

Aim:
We sought to clarify whether HCO3
-
levels have clinical relevance or prognostic impact in patients with chronic heart failure.

Methods and Results:
We conducted a prospective study involving hospitalized patients with stage C/D heart failure and measured HCO3
-
levels in arterial blood gas samples prior to discharge. We enrolled a total of 718 patients (mean 68.3 years old and 62.1% male), with neutral pH ranging from 7.35 to 7.45, and found that 132 (18.4%) had HCO3
-
levels exceeding 26 mmol/L. Patients with HCO3
-
> 26 mmol/L were more likely to be male and to use loop diuretics, and had higher serum sodium, as well as lower potassium levels, compared to those with HCO3
-
<
26 mmol/L, whereas there were no differences in B-type natriuretic peptide levels or left ventricular ejection fraction between the two groups. In a Kaplan-Meier analysis, patients with HCO3
-
> 26 mmol/L had lower event-free survival rates from cardiac deaths and decompensated heart failure as well as the composite of the cardiac events over a median follow-up period of 1540 days (
Figure
). In a multivariable Cox proportional hazard model after adjusting confounding variables, the presence of HCO3
-
> 26 mmol/L was independently associated with increased risks of the composite of cardiac events (hazard ratio, 1.64; P < 0.01).

Conclusion:
Elevated HCO3
-
levels may indicate enhanced proximal nephron activation and resistance to loop diuretics, which predicted adverse outcomes in patients with chronic heart failure, even within a normal pH range.
Abstract 12365: Liraglutide Improves Myocardial Stress Perfusion and Energetics in Patients With Type 2 Diabetes- A Randomised, Single Centre, Open Label, Cross-Over Drug Trial
Authors: Chowdhary Amrit , Thirunavukarasu Sharmaine , Jex Nicholas , Akkaya Sevval , Kotha Sindhoora , Giannoudi Marilena , Procter Henry , Kellman Peter , GREENWOOD John , Plein Sven , Levelt Eylem
Published: December 2023

Background:
Insulin secretion and insulin resistance in Type 2 diabetes (T2D) are amenable to pharmacological intervention. In a single center, open-label, randomized, cross-over drug trial we compared two glycaemic control strategies using Glucagon-like peptide-1 receptor agonists liraglutide and peroxisome proliferator activated receptor-gamma agonist-pioglitazone to see the effect on myocardial perfusion, energetics and function.

Methods:
Forty-one eligible patients with T2D and no known prior CV disease were randomized in a 1:1 ratio to the study drugs for a 16-week treatment period followed by an 8-week washout and a further 16-week treatment period for the second drug. Participants underwent rest and dobutamine stress
31
phosphorus magnetic resonance spectroscopy followed by CMR scans. The CMR protocol consisted of rest and dobutamine stress cine imaging, perfusion imaging and late gadolinium enhanced imaging immediately before and after each treatment arm.

Results:
Liraglutide therapy resulted in significant reductions in the body mass index. Pioglitazone led to a significant increment in LV mass. Liraglutide therapy resulted in increased rest and dobutamine stress energetics, global stress myocardial blood flow and myocardial perfusion reserve. With pioglitazone treatment, an isolated increase in the E/A was observed.

Conclusions:
In this study we showed for the first time that four months treatment with GLP-1RA (liraglutide) results in significant improvements in myocardial perfusion and energetics, while the insulin sensitiser pioglitazone shows no effect in modulation of these parameters.
Abstract 12414: Aggregated Data Masks Racial and Ethnic Disparities in Cardiometabolic Disease Prevalence
Authors: Koyama Alain , Bullard Kai , Miyamoto Yoshihisa , Saelee Ryan , Jackson Sandra , Pavkov Meda , Xu Fang , Onufrak Stephen
Published: December 2023

Background:
Although data disaggregation can unmask important differences in health disparities among subgroups, prevalence of cardiometabolic diseases among disaggregated racial and ethnical subgroups in the United States is inadequately characterized.

Research Question:
How does prevalence of diagnosed cardiometabolic diseases among US adults vary by racial and ethnic subgroups?

Methods:
A total of 3,970,904 US adults aged ≥18 years were identified from the Behavioral Risk Factor Surveillance System, 2013-2021. Prevalence of each cardiometabolic disease (diabetes, myocardial infarction, angina or coronary heart disease [CHD], stroke) was based on self-reported diagnosis by a healthcare professional, adjusting for age, sex, and survey year.

Results:
Adjusted prevalence of diabetes was 10.9% (95% confidence interval: 10.8-11.0%) in the total population, ranging from 9.1% (9.0-9.1%) among Non-Hispanic (NH) White adults, to approximately 16% among NH American Indian/Alaska Native, NH Black, and NH Pacific Islander adults. Diabetes prevalence was 11.5% (11.0-12.0%) for the aggregated NH Asian category, but ranged from 6.3% (4.7-8.4%) in the Vietnamese subgroup to 15.2% (13.8-16.8%) in the Filipino subgroup. Additional adjusted overall prevalences were myocardial infarction 4.3% (4.3-4.3%), angina or CHD 4.1% (4.1-4.2%), and stroke 3.2% (3.1-3.2%). Within the Hispanic subgroups, reported prevalence of angina or CHD ranged from 3.1% (2.3-4.0%) to 6.3% (6.0-6.6%) among Cuban and Puerto Rican subgroups, respectively.

Conclusion:
Prevalence of diagnosed cardiometabolic diseases varied considerably among racial and ethnic subgroups, highlighting the utility of data disaggregation in accurate characterization of health disparities within specific racial and ethnic populations. Such data can be used to better tailor disease prevention programs to disproportionately-affected subpopulations.
Abstract 12418: Effect of Atrial Fibrillation Cardioversion on the Severity of Mitral Insufficiency
Authors: Al Sallamin Isaac , Mtour Sameer M , Nassar Monther , Pham Richard
Published: December 2023

To evaluate the effect of cardioversion with restoration of sinus rhythm in patients with atrial fibrillation (AF) and significant mitral regurgitation (MR) may improve the severity of MR. Atrial fibrillation (AF) is chronic, progressive and, may cause "permanent remodeling of the heart muscle, without structural abnormalities of the valve, reverse remodeling of the left atrium (LA) may be successful in AF. This retrospective cohort study included patients with atrial fibrillation who were hospitalized for cardioversion, received echocardiography during AF in mitral insufficiency, demonstrated significant mitral regurgitation, and underwent additional echocardiography within six months. Indices of the two echocardiograms were compared and used to investigate the effect of cardioversion on the severity of MR. A total of 417 patients were enrolled with a mean age of 74.6 ± 12, with 192 men (46%). On a 6 month follow-up echo, 254 patients (61%) returned to sinus rhythm. An improvement of two or more degrees of severity of MR was observed in 100 patients (24%). Of that number, 72 patients (72%) returned to sinus rhythm, compared with 28 patients (28%) who remained in AF (p = 0.009). Multivariate analysis found that the restoration of sinus rhythm was independently associated with an improvement of two or more degrees of severity, MR p = 0.01, OR = 1.9, CI 95% [1.2-3.0]. There was improvement in the end systolic left ventricular diameter from 3.79 ± 0.99 to 3.58 ± 0.91, p < 0.01, a decrease in the diameter of the left atrium from 4.97 ± 0.64 to 4.79 ± 0.76, p < 0.02, a decrease in the jet area from 11.37 ± 3.7 to 5.9 ± 1.7, p < 0.01, a decrease in vena contracta from 0.66 ± 0.08 to 0.56 ± 0.07, p < 0.01, and a decrease in the TIG from 41.85 ± 12.9 to 36.5 ± 10.7, p < 0.01. There was also an improvement in the FS indices from 28.70 ± 10.17 to 32.17 ± 9.28, p < 0.01.In the group with a slight improvement or no improvement in MR, there was an increase in end diastolic diameter from 5.10 ± 0.77 to 5.19 ± 0.79, p < 0.02, and an increase in the diameter of the left atrium. There was no difference in the other indices. Cardioversion of atrial fibrillation to sinus rhythm in patients with significant mitral regurgitation was positively related to improvement in the severity of mitral insufficiency.
Abstract 12477: ER Stress Chop Depletion in Endothelial Cells Protects From Renovascular Hypertension Pathogenesis
Authors: SRINIVAS BALAJI , Belmadani Souad , Matrougui Khalid
Published: December 2023

Introduction:
Renovascular hypertension poses a significant risk for cardiovascular diseases, with endoplasmic reticulum (ER) stress playing a critical role in their development. However, the specific impact of ER stress-induced C/EBP homologous protein (CHOP) expression in endothelial cells on renovascular hypertension-induced cardiovascular complications remains unexplored. This study investigates the effects of disrupting ER stress CHOP in endothelial cells on microvascular dysfunction associated with renovascular hypertension.

Hypothesis:
We hypothesize that deleting ER stress CHOP in endothelial cells (EC) can mitigate renovascular hypertension-induced vascular endothelial dysfunction.

Methods:
Eight-week-old male and female mice (CHOP
flx/flx
and EC
CHOP-/-
) were divided into eight groups: control groups undergoing a sham operation for 4 weeks and renovascular hypertension groups subjected to 2-kidney-1-clip (2K1C) surgery for 4 weeks. Body weight, blood pressure, running performance, cardiac hypertrophy and fibrosis, lung edema, inflammation, vascular endothelial function, and signaling were assessed.

Results:
Male and female CHOP
flx/flx
mice subjected to 2K1C for four weeks exhibited hypertension, cardiac hypertrophy and fibrosis, lung edema, impaired running performance, and endothelium-dependent vascular relaxation dysfunction. In contrast, male and female EC
CHOP-/-
mice subjected to 2K1C for four weeks were protected against the pathogenesis of renovascular hypertension. Furthermore, mesenteric resistance arteries from CHOP
flx/flx
mice displayed reduced endothelial nitric oxide synthase (eNOS) phosphorylation, while EC
HOP-/-
mice showed no such effect.

Conclusions:
These findings emphasize the significance of targeting ER stress CHOP in endothelial cells of male and female mice to protect against the development and pathogenesis of renovascular hypertension.
Abstract 12622: Long Term Use of Adaptive Servo Ventilation Improves and Maintains Cardiac Function in Patients With Heart Failure With Central Sleep Apnea and Prevents Readmission Due to Worsening Heart Failure Compared to Short Term Use
Authors: Ikeda Tatsunori , Murai Hisayoshi , Fujimoto Manabu , Hirai Tadayuki , Usui Soichiro , Takamura Masayuki , Ikeda Keiko , Okeie Kazuyasu
Published: December 2023

Introduction:
Central sleep apnea (CSA) is closely associated with poor prognosis in heart failure (HF) patients. Adaptive servo-ventilation (ASV) was expected as a new treatment for HF patients with CSA. However, the efficacy of ASV is controversial, especially the efficacy of long-term use has remained unclear.

Methods:
We retrospectively examined all HF patients with CSA treated with ASV seen between May 2008 and November 2022 in our hospital who had not been admitted to the hospital due to worsening HF in the 6 months before initiating ASV therapy. We divided them into 2 groups: (A) non-continues-ASV-treated patients; (B) continues-ASV-treated patients. The outcome was a composite of readmission due to worsening HF and all-cause mortality.

Results:
During a median follow-up of 10.3 years after leaving the hospital, 11 patients died out of 101 patients. Twenty-two patients (group A) could not continue to use ASV because of its discomfort. Seventy-nine patients (group B) could continue to use the ASV device at night after leaving the hospital over a long period. There were almost no significant differences in the baseline characteristics between the two groups. In group B, during 6-, 12-, and 24-month observations, left ventricular ejection fraction (46.4 +/- 17.9 to 47.1 +/- 15.6, 49.8 +/- 15.8, and 48.2+/- 18.9%, p<0.05 compared with baseline) and brain natriuretic peptide (685.5 +/- 1087.2 to 233.1+/- 362.9, 391.8 +/- 929.0 and 166.9 +/- 195.1 pg/ml, p<0.05 compared with baseline) improved significantly. And there was significantly less readmission by worsening HF than in group A (log-rank P<0.001). However, there were no significant differences in all-cause mortality between the two groups (log-rank P=0.221).

Conclusions:
This study showed that long-term ASV therapy for more than 10 years reduced readmission by worsening HF with CSA patients compared to short-term use due to improved and maintained cardiac function but did not affect mortality.
Abstract 12630: Sex Differences in Patients Hospitalized With Acute Pulmonary Embolism - A Single Center Experience
Authors: Malas Waddah , Clarke Jacob , Malik Muhammad , Arora Punit , Bruno Elizabeth , Sawalski Cathryn , Greathouse Frances , Sutherland David , Shah Parth , Mujer Mark Terence , Walsh Kevin , Desai Parth , Elkaryoni Ahmed , Darki Amir
Published: December 2023

Background:
Acute pulmonary embolism (APE) is the third leading cause of cardiovascular death following stroke and myocardial infarction. Data regarding the impact of sex differences on the presentation, management, and outcomes of patients with (APE) remains limited. This study aimed to identify baseline characteristics and treatment strategies in males (M) versus females (F) from a single center experience.

Methods:
We retrospectively analyzed patients who underwent evaluation by our institutional pulmonary embolism response team for APE between 3/1/2016 and 1/1/2022. Baseline characteristics, biomarkers, and outcomes of interest were compared using Pearson’s Chi-squared test for categorical variables and Wilcoxon rank sum test for continuous variables.

Results:
The cohort included 886 patients, of whom 48.6% were females. The mean age was (61 ± 16) years. Males were more likely to be smokers (41% vs. 26 %; p<0.001), have a lower Body Mass Index (BMI) (31 ± 9 kg/m
2
, vs 33 ±10; p=0.01) and were more likely to have a history of prior stroke (12% vs 7.9%; p=0.04). The mean brain natriuretic peptide (BNP) on presentation was significantly higher in females (361 ± 624 pg/ml vs 281 ± 505; p=0.019). The mean d-dimer (F: 7,041 ± 6,438 ng/ml vs M: 9,063 ±11,447; p=0.13), troponin I (F: 1.60 ± 15.58 ng/ml vs M: 0.72±4.11; p=0.3), and lactic acid (F: 2.58 ± 3.20 mm/l vs M: 2.42 ± 2.43; p=0.6) were similar between both groups. PE severity (massive: 5.3% vs 6.4%; submissive: 58% vs: 55%; P=0.8) was similar between females and males. There were also no sex-based differences in the use of advanced therapies or outcomes. (Figure 1)

Conclusion:
In our APE cohort from a single center tertiary care center, sex differences in comorbidity profile (BMI, tobacco use, history of stroke) were observed. Females had a significantly higher BNP consistent with prior published literature. However, there were no sex-based disparities in PE severity, management, escalation of advanced therapies or outcomes.
Abstract 12695: An Atrial Fibrillation Treatment Pathway in the Emergency Department Reduces 30-day Cost of Care
Authors: Mahmood Rafat , Biese Kevin , Stearns Sally C , Armbruster Tiffany , Rosman Lindsey , Mazzella Anthony J , Gehi Anil
Published: December 2023

Introduction:
The annual cost of care for Atrial Fibrillation (AF) is estimated at $6.65 billion, with nearly 75% attributed to costs of hospitalizations. An AF treatment pathway with expedited follow-up to an AF-specialized clinic has been shown to reduce unnecessary admissions for AF and improve AF quality of care metrics.

Goal:
Evaluate differences in 30-day cost of care and discharge rate for adults presenting with AF to the emergency department (ED) before and after implementation of an AF treatment pathway.

Methods:
An AF treatment pathway with expedited follow-up to AF-specialized clinic was implemented at seven hospitals in North Carolina between 2017 to 2020. 30-day cost of care was calculated for patients presenting to ED with primary or secondary diagnosis of AF from 2016 to 2020 (N=12,543) by summing inflation-adjusted charges for initial hospital encounter, outpatient follow-up visits, and repeat hospital encounters for AF within 30 days. An adjusted quintile regression analysis and poisson regression, both with covariables of age, sex, race, CHA2DS2-VASc score and hospital site, were used to compare median 30 day cost of care and rates of ED discharge respectively.

Results:
Following implementation of the AF treatment pathway, the unadjusted median 30-day cost of care (Pre: $11,351, Post: $8,206), median initial hospital charge (Pre: $10,825, Post: $7,760), median repeat hospital encounter charge for those with repeat presentations within 30 days (Pre: $12,532, Post: $9,470) were all significantly lower (p<0.001). The adjusted median 30-day cost of care was lower (-$1532; 95% CI: $ -2001, $ -1064) and the predicted probability of discharge was greater (Pre: 61.7%, 95% CI: 60.2%, 63,2%; Post: 71.6%, 95% CI: 70.7%, 72.6%) following implementation of AF treatment pathway.

Conclusions:
Implementation of an AF treatment pathway in the ED is associated with an increase in ED discharge rate and decrease in 30 day costs of care.
Abstract 12706: The Impact of Social Determinants of Health and Lifestyle Factors on the Association of Lipoprotein(a) With Cardiovascular Outcomes in Two US Cohorts
Authors: Brandt Eric J , Kirch Matthias , Chennareddy Chaitanya , Patel Nimai
Published: December 2023

Introduction:
In European cohorts, a higher Mediterranean diet or Life’s Simple 7 (LS7) score abolished or attenuated the risk associated with increasing Lipoprotein(a) [Lp(a)] on cardiovascular (CV) outcomes. This is unstudied in US cohorts. Further, the impact of social determinants of health (SDOH) on the association of Lp(a) with CV outcomes is unstudied.

Hypothesis:
We hypothesized that SDOH and LS7 scores would attenuate the association of Lp(a) with CV outcomes in US cohorts.

Methods:
We used data from the Atherosclerosis Risk in Communities (ARIC) and the Multi-Ethnic Study of Atherosclerosis (MESA) studies. Outcomes were time until first fatal or nonfatal myocardial infarction (MI) or stroke. We performed multivariable cox proportional hazard analyses with covariates of age, gender, race and ethnicity, SDOH score, and LS7 score. We identified five SDOH in ARIC and 11 in MESA. The Lp(a) protein-mass from ARIC was tripled to be similar to the Lp(a) total-mass measurement in MESA.

Results:
ARIC included 15,072 individuals (median Lp(a) = 17.3 mg/dL (IQR 7.5, 40.6)) with 16.2 years average follow up. MESA included 6,822 individuals (Median Lp(a) = 18.3 (IQR 6.9, 43.8)) with 12.3 year average follow up. In age, gender, and race and ethnicity adjusted analyses Lp(a) was associated with MI in ARIC (HR 1.10, p<0.001) and MESA (HR 1.09, p<0.001). Lp(a) was also associated with stroke in ARIC (HR 1.08, p<0.001) but not MESA (HR 0.97, p=0.50). With SDOH and LS7 added to the model, association of Lp(a) with CV outcomes remained similar in ARIC and MESA. SDOH correlated positively and LS7 correlated negatively with MI and stroke. In MESA there was an interaction between LS7 score and Lp(a) for MI.

Conclusions:
Lp(a) remained similarly associated with CV outcomes in US cohorts after accounting for social and lifestyle factors, although LS7 score may have a small modifying effect on the association between Lp(a) and MI. SDOH and LS7 are strong predictors for CV outcomes.
Abstract 12748: Continuous Measurement of Percutaneous Oxygen Saturation During 6-Minute Walk Test is Useful for Predicting the Prognostic Risk in Patients With Heart Failure
Authors: Sunayama Isamu , Min Kyung-Duk , Orihara Yoshiyuki , Ohno Junichi , Matsumoto Yuki , Soyama Yuko , Manabe Eri , Oboshi Makiko , Azuma Kohei , Sugahara Masataka , Eguchi Akiyo , Naito Yoshiro , Asakura Masanori , Ishihara Masaharu
Published: December 2023

Background:
The 6-minute walk test (6MWT) is an established test to assess functional exercise performance and the 6-minute walk distance (6MWD) is strongly correlated with the functional capacity and the prognosis in patients with heart failure (HF). However, the clinical implication of sequential changes in percutaneous oxygen saturation (SpO2) during 6MWT has not been investigated in HF patients.

Purpose:
To prospectively clarify the association between sequential changes in SpO2 during 6MWT and prognosis in patients with HF.

Methods:
Fifty patients admitted with acute heart failure were enrolled. The 6MWT was performed at the time before discharge, after hemodynamic stability was confirmed. The average of SpO2 was calculated from data obtained at rest and during 6MWT by employing the wearable pulse-oximeter which is designed to record the SpO2 value every second. Alternations in SpO2 (ΔSpO2) were obtained by subtracting the average during 6MWT from that at rest. Patients were followed up to 9 months for the composite outcome of heart failure-hospitalization and death.

Results:
The mean age of participants was 78.8 years, and 23 (46%) were female. The mean EF was 46.1% and the number of patients with EF ≦40 was 22. The 6MWD was 250 ± 112m and the ΔSpO2 was 2.88 ± 4.3%. All cases were classified by walk distance and ΔSpO2; long- (>220m) vs. short-distance group (≦220m) and low- (<3.5%) vs. high-ΔSpO2 group (≧3.5%). There were no significant differences in cardiac parameters and respiratory function between long- and short-distance group as well as between low- and high-ΔSpO2 group. Kaplan-Meier analysis revealed that higher ΔSpO2 showed a more strong and statistically significant impact on cardiovascular outcome compared to longer 6MWD (HR=3.25, CI=1.40-7.51, p=0.006, HR=2.24, CI=0.94-5.32, p=0.067, respectively).

Conclusions:
This study showed that, compared to walk distance, ΔSpO2 during 6MWT was more predictive of the prognosis of heart failure patients.
Abstract 12766: Assessing the Economic and Clinical Impact of Surgical Aortic Valve Replacement on Patients With Symptomatic Aortic Valve Regurgitation
Authors: Still Sasha A , Ryan Michael , Gunnarsson Candace , Heidrich Natalie , Davies James E
Published: December 2023

Hypothesis:
The purpose of this study was to estimate the differences in mortality, healthcare utilization, and annualized cost among patients with symptomatic aortic regurgitation (sAR) who underwent surgical valve replacement (SAVR) compared with those that were managed non-operatively within 12 months of their diagnosis.

Methods:
Using the Optum® United Health Care Database, we identified 132,317 patients from 2016 to 2021 with a diagnosis of clinically symptomatic aortic regurgitation (sAR) who had a minimum of 6 months of continuous enrollment prior to sAR and at least 12 months of continuous enrollment following sAR and no record of aortic stenosis or transcatheter aortic valve replacement. sAR was defined as ≥ 2 visits for either heart failure, angina, dyspnea, or syncope in the presence of aortic regurgitation. Outcomes were all-cause mortality, healthcare utilization, and annualized cost. Inverse propensity score weighting (IPW) was employed to adjust for baseline differences and included patient demographics and comorbidities measured by the Elixhauser Comorbidity Index. Cox proportional hazards were used to model survival and general linear models were estimated for annualized healthcare utilization and total costs.

Results:
Among 132,317 patients identified with sAR, only 400 (0.3%) underwent SAVR within the first 12 months of their sAR diagnosis. They were younger on average 65 vs. 75 years (p<0.0001), more often male (71 vs 48%, p<0.0001), and had a slightly higher Comorbidity Index (5.1 vs. 4.8, p=0.0527). After IPW, sAR patients who had SAVR had lower mortality (HR 0.384; 95% CI 0.375-0.394; P<.0001), estimated annualized inpatient visits (0.33 versus 0.43; P=0.0039) and emergency department visits (0.54 versus 0.70; P=0.0002), hospital days (2.70 versus 3.14; P<.0001), and annualized cost ($33,744 versus $41,399; P<.0001).

Conclusion:
In this retrospective study, SAVR performed within 12 months of the diagnosis of symptomatic aortic regurgitation is associated with improved mortality and lower annualized healthcare utilization and costs. The clinical and economic benefits related to timely surgical management of aortic regurgitation should be considered when managing patients with symptomatic aortic regurgitation.
Abstract 12803: Disparities in Care Among COVID-19 Patients With ST-Elevation Myocardial Infarction Admitted in Rural and Urban Teaching Centers
Authors: Memon Rahat A , Dhaliwal Jasninder S , Ramphul Kamleshun , Kumar Nomesh , Ravalani Abhimanyu , Bawna Fnu , Sombans Shaheen , Sakthivel Hemamalini
Published: December 2023

Introduction:
During the pandemic of COVID-19, resources ran scarce in various regions, which impacted access and availability of treatment options. Our study aims to compare outcomes of COVID-19-positive patients (CPP) who reported a diagnosis of ST-elevation myocardial infarction (STEMI) in either rural centers (RC) or urban teaching centers(UTC).

Methods:
De-identified data of CPP adults with STEMI from the 2020 National Inpatient Sample for admissions between April-December 2020 were analyzed. Patient characteristics and outcomes between RC and UTC were compared.

Results:
We found 4690 STEMI cases among CPP. Most cases were hospitalized in UTC(4255 cases, 90.7%), with 9.3% seeking care RC (Table 1). Cases in UTC were younger (mean age 66.28 years) and with a higher mean Charlson Comorbidity Index (CCI) score (mean score 4.31) than those at RC (mean age 71.75 years, p<0.01, mean CCI score 4.00, p<0.01). Medicare primarily covered both centers. A higher proportion of patients in RC were Whites (77.4%), while 50.0% of AMI cases at UTC were Whites. Patients at UTC also had a higher prevalence of prior stroke (6.3% vs. 3.4%, p=0.016) and lipid disorder (53.3% vs. 43.7%, p<0.01) than those in RC but showed a lower prevalence of diabetes (44.3% vs. 50.6%, p=0.012). No differences in the prevalence of prior myocardial infarction, hypertension, smoking, obesity, chronic kidney disease, and sex were noted. Cases in UTC reported a higher incidence of cardiogenic shock (18.2% vs. 3.4%, aOR 6.631, 95% CI 3.850-11.421, p<0.01), PCI use (42.1% vs. 20.7%, aOR 2.482, 95% CI 1.910-3.225, p<0.01), and death (44.4% vs. 40.2%, aOR 1.513, 95% CI 1.197-1.912, p<0.01).

Conclusions:
Adults with COVID-19 with STEMI admitted UTC were sicker with a higher mean CCI score and reported higher PCI use and mortality. Further studies investigating the distribution of resources during the pandemic and proposals to improve care access in rural and urban teaching hospitals should be conducted.
Abstract 12854: Early and Late Features of Intracardiac Flow in Repaired Tetralogy of Fallot (rTOF) Patients Using Doppler Velocity Reconstruction (DoVeR)
Authors: Hardikar Priyanka , Meyers Brett , Sable Craig A , Vlachos Pavlos , Loke Yue-Hin
Published: December 2023

Background:
Intracardiac flow analysis has implicated flow energy loss (FEL), kinetic energy (KE) and vortex strength (VS) as markers of ventricular dysfunction in repaired Tetralogy of Fallot (TOF); no studies have investigated early vs. late intracardiac flow conditions after repair. We utilized novel echocardiography (echo) based Doppler Velocity Reconstruction (DoVeR) to determine FEL, KE and VS in pre-operative TOF vs early post-repair (<1 month) and late post-repair (>10 years).

Methods:
This was a single-center retrospective cross-sectional study on TOF patients with pre- and post-operative surveillance transthoracic echo. Apical 4 chamber color Doppler views were collected. The streamfunction-vorticity formulation was used to reconstruct left ventricular (LV) blood velocity fields by DoVeR. Velocity flow fields were evaluated for peak FEL, KE and VS. The FEL was also normalized against KE to account for physiologic variations. Data were compared via one-way ANOVA.

Results:
Echo studies from 14 pre-operative (1.7±0.5 months), 14 early-post repair (3.6±2.3 months) and 15 late-post repair (16.5±6.6 years) TOF patients were included. There was significant variation in FEL, KE, VS, and normalized FEL across timepoints (all p<0.05) (Figure B). In general, when compared to pre-operative TOF, the early post-repair cohort had lower FEL/KE/VS corresponding to reduction in ventricular volume load; however late post-repair cohort had higher FEL/KE/VS, suggestive of effects from long-term interventricular interactions.

Conclusion:
The LV intracardiac flow in TOF changes early after initial repair and late after repair. DoVeR could potentially be used to serially evaluate TOF patients.
Abstract 12877: Giant Pericardial Cyst Causing Syncope
Authors: Miller Shane , Clark Cali , Broce Ashley
Published: December 2023

A 30 year old male presented with episodes of near syncope with dizziness, palpitations, chest tightness, and left arm paresthesias. Upon presentation, his vitals were normal. Initial imaging of a chest radiograph showed an enlarged cardiac silhouette and a follow-up chest CT demonstrated a 10 cm cystic mass in the anterior mediastinum concerning for a giant pericardial cyst. Echocardiogram was performed which showed a normal ejection fraction, no valvular abnormalities, and a trivial pericardial effusion. A CT-guided drainage was performed with 440mL of fluid removed and shrinkage of the cyst to 27x63mm. The aspirate was loaded with leukocytes without organisms identified. The following day, the cyst recollected to 85x69mm. Repeat CT-guided drainage was attempted however was unsuccessful due to right pneumothorax. After resolution of the pneumothorax, he was asymptomatic prompting discharge with close outpatient follow-up. Outpatient imaging demonstrated increased size of the pericardial cyst to 11 cm in diameter. A third drainage via CT-guidance was attempted however only minimal fluid was able to be drained. As the patient remained asymptomatic, it was recommended the patient have repeat imaging in 6 months and monitor for symptoms. Pericardial cysts are relatively rare and comprise 7% of mediastinal masses. They originate from failed fusion of the mesenchymal lacunae that form the pericardial coelom. Pericardial cysts typically range from 1 to 5 cm in diameter, with those over 10cm being termed 'giant pericardial cysts'. Most cysts are asymptomatic, although if symptoms do occur they are generally in response to mass effect and compression of local structures, such as shortness of breath and chest discomfort. If a patient remains asymptomatic, conservative management with serial imaging is recommended. However, if a patient becomes symptomatic or develops complications, surgical management via a pericardectomy or percutaneous aspiration is recommended.
Abstract 12986: Aorta Gene: Polygenic Prediction Improves Detection of Thoracic Aortic Aneurysm
Authors: Pirruccello James P , Khurshid Shaan , Lin Honghuang , Weng Lu-Chen , Zamirpour Siavash , Kany Shinwan , Lindsay Mark E , Ellinor Patrick T
Published: December 2023

Introduction:
Thoracic aortic disease is an important cause of morbidity and mortality in the US, and aortic diameter is a heritable contributor to risk.

Question:
Could a polygenic prediction of ascending aortic diameter improve detection of aortic aneurysm?

Methods:
We used deep learning to measure ascending thoracic aortic diameter in 56,556 UK Biobank participants and conducted a genome-wide association study (GWAS) in 39,524. We built a 1.1-million SNP polygenic score using
PRScs
. In 4,896 non-GWAS participants (“training set”), we built linear models from clinical variables and the polygenic score (“AORTA Gene”) and simpler comparators. The models were assessed in the remaining 4,962 unrelated UK Biobank participants with imaging (“test set”). The models were externally validated in
All Of Us
participants over the age of 40.

Results:
In the test set, the AORTA Gene model explained 39.9% (95% CI 37.8-42.0%) of the variance in thoracic aortic diameter compared to 29.2% for the clinical model (95% CI 27.1-31.4%). For diameter ≥ 4cm, the area under the receiver operating characteristic curve (AUROC) was 0.834 for AORTA Gene, superior to the clinical model (0.765, P=7.3E-10). Thresholding at the top 10% of the score, AORTA Gene had a sensitivity of 52% and a specificity of 91.2% (F1: 0.197) for detecting the 113 participants with diameter ≥ 4. For the clinical score, the respective values were 36.3%, 90.9%, and 0.137.

In 610
All Of Us
participants with genetic data and aortic measurements, the AORTA Gene model had a correlation of 0.591 (95% CI 0.537-0.640) with aortic diameter
vs
0.538 (95% CI 0.479-0.592) for the clinical model (P=2.2E-13 against a null hypothesis of the genetics being uninformative beyond clinical factors). It had an AUROC of 0.827 for identifying diameter ≥4cm
vs
0.791 for the clinical model (P=7.8E-03). AORTA Gene also had a higher AUROC for prevalent thoracic aneurysm diagnoses (0.760
vs
0.739 for the clinical score, N=1,904 cases, P=2.4E-16) and incident diagnoses (0.748
vs
0.729, N=1,632 events, P=9.5E-10).

Conclusions:
Genetic information improved prediction of thoracic aortic diameter and aneurysm when added to clinical risk factors. Larger and more diverse samples will be needed to develop more powerful scores.
Retracted: Abstract 13079: Prevalence and Incidence of Transthyretin Amyloid Cardiomyopathy in the USA From 2004 to 2022: An Observational Database Study
Authors: Alexander Kevin M , Ersboell Anne S , Haase Christiane L , Mortensen Julie T , Maurer mathew S
Published: December 2023

Introduction:
Improved diagnosis and awareness have resulted in global increases in the incidence and prevalence of transthyretin amyloid cardiomyopathy (ATTR-CM). However, current US epidemiology data are lacking.

Aims:
To estimate the prevalence and incidence of ATTR-CM in a large US population and describe characteristics of patients with ATTR-CM.

Methods:
Data from 2004–2022 were extracted from TriNetX, a US database of EMRs covering in- and outpatient data. An algorithm using ICD-9/10 codes and RxNorm codes for clinical drugs (amyloidosis + cardiac manifestation – light chain amyloidosis) was used to identify patients with ATTR-CM. Included were adults ≥ 18 years old at index date (first ATTR-CM diagnosis per the algorithm) with ≥ 1 year of database history. The incidence and prevalence of ATTR-CM were assessed annually. Demographic characteristics at index and ATTR-CM-related comorbidities any time pre-index were assessed in cross-sectional cohorts over time.

Results:
In total, 12 209 patients were identified (2004–08, n = 332; 2009–13, n = 913; 2014–18, n = 3392; 2019–22, n = 7572). The incidence and prevalence of ATTR-CM per 100 000 people increased over time (incidence, 2004: 3.7; 2022: 11.5; prevalence, 2004: 5.1; 2022: 35.1) (
Figure
). Across cohorts, approximately 40% of patients were women, and 20% were Black. Median age increased over time (2004–08: 65 years; 2019–22: 74 years). In the 2019–22 cohort, the cardiac manifestations of ATTR-CM were cardiomyopathy (56.3%), atrial fibrillation (56.1%), and heart failure (20.9%). The proportion of patients with ATTR-CM-related comorbidities increased over time (2004–08 vs 2019–22: polyneuropathy, 15.1 vs 19.0%; carpal tunnel syndrome, 10.5 vs 13.4%; lumbar spinal stenosis, 4.2 vs 13.3%; aortic stenosis, 9.3 vs 13.2%).

Conclusion:
In this US population, the incidence and prevalence of ATTR-CM diagnoses increased over 19 years. Age at diagnosis and ATTR-CM comorbidity burden increased during this period.
Abstract 13091: Chronic Thromboembolic Pulmonary Hypertension Associated With Prolonged Use of Combined Oral Contraceptives in a 27-Year-Old Woman: A Successful Case of Pulmonary Endarterectomy
Authors: Munoz-Moreno Juan-Manuel , Requena Armas Carlos , Aguirre-Zurita Oscar
Published: December 2023

Introduction:
Chronic thromboembolic pulmonary hypertension (CTEPH) is associated with venous thromboembolism (VTE); however, in half of the cases, no prior deep vein thrombosis is ever found. The use of combined oral contraceptives (COCs) is a known risk factor for VTE. We present the case of a young woman with CTEPH in whom timely diagnosis and intervention prevented irreversible pulmonary hypertension (PH).

Case Presentation:
A 27-year-old woman with 10-year use of COCs presented with progressive dyspnea for 3 weeks. The ECG showed right ventricular systolic overload and right atrial enlargement. Laboratory tests showed elevated pro-BNP and D-dimer. TTE showed right atrium and right ventricle (RV) enlargement and elevated right ventricular systolic pressure (RVSP) of 83 mmHg. The ventilation/perfusion scintigraphy showed mismatched segmental perfusion defects in both lung fields with greater involvement of the left lung, and oral anticoagulation was started. Lower extremity venous ultrasound and hypercoagulability studies were normal. CTPA revealed filling defects in the left main pulmonary artery and bilateral segmental branches. After 3 months of anticoagulation, she persisted in NYHA class III, and right heart catheterization showed mean PAP of 38 mmHg, PCWP of 8 mmHg, and PVR of 9 WU, confirming CTEPH. Due to unavailability in Peru, she was referred to a US center for pulmonary endarterectomy (PEA). After a successful intervention, she improved clinically with a reduction in RVSP to 34 mmHg. This case highlights the importance of rapid intervention in CTEPH even in situations where optimal treatment is not readily available.

Conclusion:
CTEPH may be associated with the prolonged use of COCs in young women. Timely intervention can reverse PH and prevent RV remodeling. Unfortunately, Peru does not have a PEA center and not every case will undergo treatment. We call for the training of local surgeons to ensure fair and equitable access for the population.
Abstract 13144: High Polygenic Risk Score is a Predictor for Major Adverse Cardiac Event
Authors: Fohle Emmanuel , Nadkarni Ninad , Oleszak Filip , Hajek Catherine , Stys Adam , Petrasko Marian S , Rajpurohit Naveen , Larson Eric , Bartaria Shubhi , GU SHAOPENG , Weaver Max , Rotter Jerome I , Guo Xiuqing , Stys Tom
Published: December 2023

Background:
The polygenic risk score for coronary artery disease (CAD PRS) is an emerging CAD risk assessment tool. It is unclear if it improves predictive value for major adverse cardiovascular events (MACE). This study aims to investigate the value of PRS as predictor for MACE.

Methods:
Patients who had coronary calcium score (CAC) within the Sanford Heart Screening Program were enrolled in the study from 2011-2021. They were genotyped using Illumina Global Screening Array version 1. PRS was calculated using a literature derived list of 180 single nucleotide polymorphisms. Patients were classified into 3 groups based on CAD PRS: high PRS (> 85
th
percentile), moderate PRS (15
th
to 85
th
percentile) or low PRS (<15
th
percentile). MACE was defined as the composite of death, myocardial infarction, coronary revascularization and heart failure hospitalization.

Results:
A total of 1,380 patients with mean age of 57.76± 9.76 were analyzed of which 6.6% had MACE. Chi-square test revealed a significant relationship between PRS (low, moderate, high) and a future MACE event, [X
2
(N=1380) = 9.9,p < .01]. Post-hoc testing showed that those with high PRS(standardized residuals = 3.14, p < .01) were more likely to have a future MACE event than those with a moderate (standardized residuals =1.59, p=.68) or low PRS (standardized residuals =1.11, p = 1) (Figure 1).

Conclusions:
This study shows that high CAD PRS has an added value in predicting future MACE in general population as represented in our Sanford Heart Screening Program.
Abstract 13180: Cardiovascular Disease and Cholesterol Lowering Therapy in Women and Men With Molecularly Proven Familial Hypercholesterolemia
Authors: Maia Kleisson A , Miname Marcio H , Maia Flavia C , Rocha Viviane Z , Chacra Ana P , Mizuta Marjorie , Jannes Cinthia Elim , Pereira Alexandre , Krieger Jose E , Santos Raul D
Published: December 2023

Introduction:
Familial Hypercholesterolemia (FH) is an autosomal dominant disease affecting women and men on the same proportion. There is scant evidence on cardiovascular disease (CVD) and therapy adequacy on contemporary FH cohorts according to sex.
Goals:
Evaluate whether there were differences in CVD outcomes and treatment intensity in women and men with molecularly proven FH at a specialized lipid clinic.

Methods:
Initially a cross-sectional analysis of 801 patients with FH enrolled between 2011 and 2022 on a genetic cascade screening program was done
.
All had a positive FH molecular diagnosis. Participants were then followed by a median of 5 years (0.08 to 11 years). Clinical, laboratory and, treatment parameters were compared at baseline and during follow-up according to sex.

Results:
The cohort consisted of 455 women (57%) and 346 men (43%), mean age 47± 15 years. At baseline there were no sex differences regarding LDL-C (196±74 mg/dL men vs 200±75 mg/dL women, p= 0.567) as well as percentage of those with LDL-C < 100 mg/dL (6.8% men vs 6.1% women, p=0.712) or < 70 mg/dL at baseline (0.3% men vs 0% women, p=0.238). Intensive lipid lowering treatment use was similar between men and women at baseline (75.1% vs. 74.4%; p= 0.848) and during follow-up (87.6% vs. 88.3%; p= 0.785). At baseline 23.1% of women and 38.1% of men had a previous history of CVD (p= 0.000). After follow-up, 41 women (9%) and 52 men (15%) had an incident CVD event (p=0.009). Multivariate Cox regression analysis showed that risk factors related to incident events were age (HR=1.028, 95% CI 1.005-1.052 per year, p =0.019), presence of corneal arcus (HR 1.794, 95% CI 1.096-2.937, p= 0.02), current smoking (HR 2.534, 95% CI 1.304-4.927, p=0.006) and a previous CVD event (HR= 1.793, 95%CI 1.041-3.087, p= 0.035).

Conclusions:
Overall FH men had a greater risk of CVD events than FH women. There was no difference in treatment intensity and CVD outcomes were associated with traditional risk factors or previous CVD.
Abstract 13208: A Small Molecule Macrophage Migration Inhibitory Factor Agonist Ameliorates Age-Related Myocardial Intolerance to Ischemia-Reperfusion Insults
via
Metabolic Regulation
Authors: Wang Hao , Slotabec Lily , Didik Steven , James Adewale , Li Ji
Published: December 2023

Introduction:
The macrophage migration inhibitory factor (MIF) is emerged as a critical mediator during myocardia ischemia and reperfusion (I/R). An impaired MIF signaling is occurred in aging. MIF agonist, MIF20, can argument cardiac MIF signaling through increasing the binding affinity between MIF and its receptor, CD74/CD44.

Hypothesis:
Administration of MIF20 can increase the resistance of aged myocardium to ischemic insults caused by I/R
via
modulating the MIF signaling regulated energy metabolism.

Methods:
Young (3-5 months) and aged (24-26 months) wild-type C57BL/6J mice, cardiomyocyte specific MIF knock out C57BL/6J mice (cMIF-/-) and wild type littermates (MIF

flox/flox

) were injected with MIF20 (0.15 μg/kg, I.V.) 5 minutes before reperfusion after 45 minutes of ischemia. The left ventricular myocardium was for immunoblotting, NAD/NADH assay, and metabolomics analysis. The working heart perfusion and the SeaHorse system were for metabolic measurements.

Results:
The small molecule MIF agonist, MIF20, which binds to MIF to increase signaling through its cognate receptor CD74/CD44 not only decreases infarct size but also preserves cardiac systolic function in the aged versus young hearts. MIF20 contributes to the maintenance of mitochondrial fitness and preserves the contractility of cardiomyocytes under hypoxia and reoxygenation stress. These beneficial effects of MIF20 are reduced in cardiomyocyte-specific MIF knock-out (cMIF
-/-
) versus littermates (MIF

flox/flox

) mice, supporting the autocrine role of MIF in mediating ischemic cardiac protection. The age-related disruption of metabolic homeostasis in aged versus young hearts was modulated by MIF20’s ability to upregulate glucose oxidation and downregulate the oxidation of fatty acid. These actions were associated with an upregulation of pyruvate dehydrogenase kinase 4 (PDK4) and downregulation of Long-chain acyl-CoA dehydrogenase (LCAD). MIF20 as MIF signaling agonism modulation of metabolic adaptation in aged hearts further led to reduced generation of reactive oxygen species (ROS) in the myocardium.

Conclusions:
MIF agonists such as MIF20 may have a therapeutic role by limiting cardiac damage and rescuing cardiac dysfunctions of senescent hearts to I/R stress.