bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 4147421: Disparities in Myocardial Infarction Mortality among Patients with Chronic Obstructive Pulmonary Diseases: A 22-Year Retrospective Analysis
Authors: Ahmad Muhammad , Shehzad Mustafa , Khan Dawlat , Shehzad Dawood
Published: November 2024

Background:
COPD and cardiovascular disease (CVD) share common risk factors. Myocardial Infarction (MI) is a major cause of death in patients with COPD; however, temporal, sex-based, racial, and geographic variations in mortality are poorly defined.

Methods:
We conducted a retrospective analysis using the CDC WONDER dataset, extracting age-adjusted mortality rates (AAMR) per 100,000, calculating the annual percentage change (APC) and its weight average, the average annual percentage change (AAPC) through Joinpoint regression. The results were stratified to identify temporal, sex-based, racial, and geographic variations in mortality.

Results:
From 1999–2020, a total of 191,215 deaths among adults over 25 years old with COPD were attributed to MI. During this period, the AAMR declined significantly, from 6.83 to 2.76, reflecting an average annual percentage change (AAPC) of -4.54% (95% CI: -4.79 to -4.31). Males exhibited a higher AAMR (5.57; 95% CI 5.54 to 5.60) than females (2.88; 95% CI 2.86 to 2.90). Both sexes experienced a marked decline in AAMR over the study duration. Non-Hispanic (NH) Whites had the highest AAMR (4.43), followed by NH blacks (3.03), NH American Indians/Alaskan Natives (3.57), Hispanics or Latinos (1.90), NH Asians/Pacific Islanders had the lowest AAMR (1.28). Significant state-wise variations were observed, with AAMRs ranging from a high of 7.57 in West Virginia to a low of 1.47 in Hawaii. Three states—Arkansas, New Mexico, and South Dakota—reported an overall increase in AAMRs over the study duration. Regionally, the Midwest exhibited the highest AAMRs (4.52), while the Northeast had the lowest (3.51). Additionally, micropolitan (5.89) and noncore (6.30) areas experienced higher AAMRs compared to large central metropolitan areas (3.14).

Conclusion:
Mortality from acute MI in patients with COPD has decreased overall. However, certain sociodemographic groups have not secured the same deceleration in mortality. Opportunities to decrease COPD-related death rates still exist.
Abstract 4147424: In hospital Outcomes of Acute Myocarditis in Adults with Systemic Inflammatory Disease: A Population-based Analysis in The United States
Authors: ODUGBEMI OLUFEMI
Published: November 2024

Systemic inflammatory diseases (SID) are associated with adverse cardiovascular (CV) events, due to derangement in innate immunity. Understanding the association with acute myocarditis (AMC) is crucial for preemptive management strategies and improving patient outcomes.

Methods:
We identified and compared adults (>18 years) with SID vs. non-SID patients hospitalized with AMC using the National In-patient sample database from 2016-2020. Six SID were selected based on HLA antigen distribution. The risks of all-cause mortality and major adverse cardiac and cerebrovascular events (CVA, cardiac arrest, acute heart failure (AHF), Ventricular arrhythmia, complete AV block, AMI, and PCI), and use of mechanical circulatory support (MCS) were assessed in adult AMC admissions with and without SID. SID were divided into 6 cohorts: SLE, RA, psoriasis (PS), IBD, Hashimoto thyroiditis (HT), and multiple sclerosis (MS) subgroups.

Results:
Overall adults AMC admissions were 26,475. The rate of AMC in non-SID was 96%. Mean age of non-SID were similar in 4 cohorts, but relatively older in RA subgroup (47.5 vs 61.5 years). We observed male predominance in the PS vs IBD groups (62% vs 51% vs 63%), but more females in the SLE, RA, HT, and MS cohort. We observed comparable mortality (aOR 1.425; CI 0.062-10.23 p=0.862) and MACE (aOR 0.943; CI 0.398-2.231 p=0.894) rates across all studied subgroups. The RA-AMC cohort had significantly higher odds of MCS use (aOR 3.8; CI 1.52- 9.55, p=0.004), after adjusting for significant confounders. The IBD-AMC cohort had significantly reduced odds of AHF (aOR 0.28; CI 0.076 - 0.99, p=0.04). However, the odds of AMI and VA were not statistically significant.(Table 1)

Conclusions:
The RA-AMC cohort are about 4 times more likely to require mechanical circulatory support during hospitalization for acute myocarditis, while IBD-AMC are less likely to have AHF. Prospective studies would be required to further examine the cardiovascular outcome in this cohort. Prospective studies would be required to further examine the cardovascular outcomes in this cohort.
Abstract 4147449: Endothelial microRNAs as New Biomarkers in Patients with Diabetes and INOCA: Insights From a Multicenter Study
Authors: Mone Pasquale , Ferrone Marco , Ciccarelli Michele , Varzideh Fahimeh , Minicucci Fabio , Kansakar Urna , Gambardella Jessica , Tesorio Tullio , Santulli Gaetano
Published: November 2024

Background:
Diabetes mellitus (DM) and hyperglycemia are known to drive endothelial impairment and coronary microvascular dysfunction. However, currently no established biomarkers of endothelial dysfunction in patients with "Ischemia with non-obstructive coronary artery" (INOCA). We evaluated the expression of circulating microRNAs (miRs) involved in the regulation of endothelial function in individuals with confirmed INOCA, comparing patients with and without DM.

Methods:
We evaluated consecutive INOCA patients referred for percutaneous coronary intervention (PCI) in a multicenter study. DM was defined according to the American Diabetes Association (ADA) guidelines. INOCA was defined based on symptoms of myocardial ischemia, non-obstructive coronary artery stenosis (<50% diameter reduction or fractional flow reserve >0.80), objective evidence of myocardial ischemia, and impaired coronary microvascular function (coronary flow reserve ≤2.0, abnormal coronary microvascular resistance indices, coronary microvascular spasm, endothelial dysfunction with ≥20% luminal constriction during acetylcholine infusion, or coronary slow flow phenomenon). Circulating miRs were isolated from plasma samples using EDTA-containing tubes and the miRNeasy Serum/Plasma kit. Quality control included using the Agilent Small RNA Kit [33] and the RNA Spike-in kit (Qiagen) with synthetic RNA spike-ins (UniSp2, UniSp4, UniSp5) and UniSp6 spike-in and cel-miR-39-3p for cDNA synthesis control. Relative gene expression was determined using the 2-ΔΔCT method, with miRs miR-125a-5p and miR-19a-5p selected for normalization using bioinformatic algorithms. Hemolysis was assessed by measuring absorbance at 414 nm and ΔCq of miR-16-5p, miR-451a, and miR-23a-3p.

Results:
42 patients completed the study (28 without DM, 14 with DM). We measured the expression levels of validated miRs and found that in INOCA patients with DM, there was increased expression of miRs associated with endothelial dysfunction and reduced expression of miRs protective for endothelial function. Specifically, miR-363-5p was significantly downregulated (P<0.001), and miR-92 was significantly upregulated (P<0.001) in individuals with DM.

Conclusions:
Our results revealed significant dysregulation of miR-363-5p and miR-92a-3p in INOCA patients with DM compared to those without DM, supporting their role as biomarkers for endothelial dysfunction in DM and INOCA.
Abstract 4147462: Ambulatory Breath Analyzer for Measuring Cardiac Output
Authors: Hale Joshua , Kolomenski Alexandre , Schuessler Hans , Tong Carl
Published: November 2024

Background:
Knowing heart failure patients’ cardiac output at outpatient setting can guide optimization of medical therapy and detect decompensation early to trigger timely response; therefore, following patients’ cardiac output has potential to greatly improve care of heart failure patients. Unfortunately, an easy to use ambulatory device that can measure cardiac output at patients’ homes currently does not exist.

Hypothesis:
One can derive cardiac output by measuring carbon dioxide (CO
2
) and flow of exhaled breath because right heart delivers CO
2
laden blood to the lungs, right heart = left heart in blood flow.

Method:
We made a novel breath analyzer that measures cardiac output from exhaled breath. This device uses [CO
2
] and volume of exhaled breath as input. Exhaled flow rate of CO
2
is measured, then divided by the difference between venous and arterial [CO
2
]. The difference is calculated from exhaled CO
2
input to a novel formula. We built and tested a prototype to implement this method. We designed a heated breath flow path with baffles to combat the high humidity in breath. Custom software then calculates cardiac output in real time. We used this prototype to measure the cardiac output at rest and after set pace treadmill jogging.

Results:
The prototype (fig) featured small dimensions, light weight, and compatibility with a typical laptop computer. Reliability testing showed a 1.85% standard deviation in volume detection over 70 test breaths. Carbon dioxide detection was compared to high-sensitivity cavity ringdown spectroscopy with an error of 1.14%. Measurement of cardiac output was performed on 11 human volunteer subjects. Echocardiogram of stroke volume X heart rate was used as reference. Cardiac output measurements from our device correlated strongly with echocardiogram reference both at rest and after exercise, giving an R=0.83 and p=3X10
-6
.

Conclusions:
We developed a novel method and device that measures cardiac output from exhaled breath, understanding that further validation in heart failure population is needed. This device can be used to measure cardiac output at outpatient settings to improve the quality of care for a great many patients.
Abstract 4147497: Post Cardiac Arrest Temperature Management: Therapeutic Normothermia and Hypothermia Effect on Cardiac Function
Authors: Pichs Diez Armando , Rawlley Bharat , Ngembus Ngonack , Anuforo Anderson , Chaudhuri Debanik
Published: November 2024

Background:
There is strong data about the neuroprotective effects of targeted temperature management (TTM) in patients post cardiac arrest, however, there is limited literature on the cardiac effects. We evaluate the impact of targeted normothermia (TN) vs targeted hypothermia (TH) on left ventricular ejection fraction (LVEF). We hypothesized that targeted hypothermia would be more cardioprotective than targeted normothermia, thus manifesting in improved LVEF and/or reduced incidence of new heart failure at various points in time.

Method:
We queried the TriNetX Global collaborative network for adult (≥18 years) patients with LVEF >50% who suffered a Cardiac arrest (CA) and Coma within one day of CA, and we created two groups: therapeutic hypothermia and therapeutic normothermia. TTM was identified with International Classification of Diseases 10th edition (ICD-10) Procedure codes 6A4Z0ZZ, 6A4Z1ZZ, and SNOMED code 308693008 and the TN group excluded patients with documented temperature ≥ 99.6 °F or ≤ 97.6 °F within 1 day of CA. Similarly, the TH group was identified using the same ICD codes and excluded patients with documented temperatures ≥96.7°F or ≤ 91.3°F within 1 day of CA being excluded. Propensity Score Matching (PSM) done for age, race, sex, and multiple cardiovascular comorbidities. Outcomes were measured at 3-, 12-, and 36 months post-CA included the risk of LVEF ≤ 50%, new onset heart failure, and new prescription of loop diuretic.

Results:
After PSM 510 patients were analyzed, with 255 well-matched subjects in each group. At 3 months there were no significant odds of TH causing a decrease in cardiac ejection fraction to 50% or less (Odds Ratio [OR] 0.90, 95% CI: 0.37 – 2.18) compared to TN. No significant difference was seen at 12 months (OR 0.897, 95% CI: 0.37 – 2.18) or 36 months (OR 0.71, 95% CI: 0.32 – 1.60). Other outcomes at 3 months without significant difference include new HF (OR 0.97, 95% CI: 0.39 – 2.43), and new loop diuretic (OR 0.77, 95% CI: 0.33 – 1.80). These odds were similarly not significant at 12 and 36 months.

Conclusions:
In post-CA patients who received TTM, no cardioprotective effects were appreciated between hypothermia compared to normothermia at 3-, 12-, and 36 month follow up. There was no difference in new diagnosis of HF post-CA or new loop diuretic prescription. With the understanding that TN has fewer side effects than TH then the results reinforce the use of TN post cardiac arrest.
Abstract 4147521: Use of an ETCO
2
-Directed Resuscitation Algorithm in a Pediatric Swine Model of Asphyxial Cardiac Arrest
Authors: OBrien Caitlin , Javdan Cameron , Powers Izabel , Lage Larraine , Donohue Christopher , Koehler Raymond , Shaffner Donald
Published: November 2024

Introduction:
Current pediatric cardiopulmonary resuscitation (CPR) guidelines provide uniform recommendations for resuscitative efforts, including chest compression rate (CCR), chest compression depth, and epinephrine administration interval (EAI), despite differences in cardiac arrest etiologies or in the patient’s response to resuscitative efforts. Titration of the CCR or the EAI based on the patient’s physiologic response to resuscitation could individualize and optimize resuscitative efforts. Our research group has previously found that use of an end-tidal carbon dioxide (ETCO
2
)-directed algorithm to titrate the CCR and EAI improved intra-arrest hemodynamics and short-term survival in a swine model.

Research Question:
Here, we investigated whether the use of this ETCO
2
-directed resuscitation algorithm improved long-term survival and neuropathologic outcomes in a similar swine model of cardiac arrest.

Methods:
We performed 46 resuscitations in 4-5 kg swine. Pigs underwent 7 minutes of asphyxia, 30 seconds of ventricular fibrillation, and 10 minutes of resuscitation prior to the first defibrillation. Pigs were randomized to standard CPR or ETCO
2
-directed algorithm CPR. A sham group was also studied. In the standard group, chest compressions were performed at 100 compressions/minute and epinephrine was administered every 4 minutes per standard pediatric guidelines. In the algorithm group, the CCR was increased by 10 compressions/minute for every minute that the ETCO
2
was <30 torr and the EAI was increased up to every two minutes. Pigs that achieved return of spontaneous circulation (ROSC) were extubated and survived 3 days. Daily neurobehavioral assessments were performed. In blinded fashion, viable and ischemic neurons were counted in the basal ganglia.

Results:
The rate of ROSC was similar in the standard (10/24, 42%) and algorithm (10/22, 46%,
p
>0.99) groups. The rate of 3-day survival was also similar between the two groups (4/24 [17%] in the standard group and 6/22 [27%] in the algorithm group,
p
=0.48). The standard and algorithm groups both had fewer viable neurons and more ischemic neurons in putamen than shams (
p
<0.01 for all pairwise comparisons, Figure 1). The number of viable and ischemic neurons were similar between the two CPR groups.

Conclusion:
In this model of pediatric asphyxial cardiac arrest, use of an ETCO
2
-directed resuscitation algorithm did not improve the rate of ROSC, 3-day survival, or neuropathologic injury in the basal ganglia.
Abstract 4147530: Artificial Intelligence Predicted Age using the Electrocardiogram Predicts Mortality in Adults with Congenital Heart Disease.
Authors: Anjewierden Scott , Madhavan Malini , Attia Zachi , Lopez-Jimenez Francisco , Friedman Paul , Egbe Alexander , Connolly Heidi , Asirvatham Samuel , Burchill Luke
Published: November 2024

Background:
Artificial intelligence (AI) can be used to predict a person’s age from the electrocardiogram (ECG) (AI-ECG age) and has been proposed as a measurement of biological age. The difference between AI-ECG age and chronological age (defined as delta-age) is an independent predictor of mortality in the general population. This study assessed the relationship between AI ECG estimated age and mortality among adults living with congenital heart disease (CHD).

Methods:
A previously validated neural network to estimate AI-ECG age was used to analyze standard digital 12-lead ECGs in a cohort of subjects aged >18 years seen in the adult CHD (ACHD) clinic between 1992 to 2023. A single ECG, collected during the year of the first visit to the ACHD clinic was analyzed to compute the delta-age.. A positive delta-age indicates an AI ECG estimated age higher than the subject’s chronological age. The relationship between the delta-age and mortality was evaluated using Cox proportional hazard models adjusting for influential clinical factors including chronologic age, sex, ACHD severity, NYHA class and history of arrhythmia.

Results:
Of 5,780 subjects tested (50% females), the mean chronological age was 39.1 ± 15.0 years. AI ECG estimated age was 52.3 ± 16.6 years. Complexity of CHD was classified as mild, moderate, and severe in 7.4%, 73.9% and 18.7% of patients respectively. Patients with severe CHD had the highest delta-age of 17.1 (±18.2) years followed by moderate 12.7 (±13.6) y and simple 7.7 (±11.5) y. Patients with single ventricle had the highest deviation in AI estimated age [median delta-age 21.0 (IQR 28.6) y] followed by those with a systemic right ventricle [median delta-age of 16.3 (IQR 29.3) y]. During a median follow-up of 6.4 y (25th – 75th centile 1.58 – 13.7 y), mortality occurred in 839 (14.5%) patients. After adjusting for chronological age, CHD severity, and other clinical variables, delta-age gap was associated with increased mortality risk (HR 1.06 (1.03 – 1.09) per 5-year increment in delta-age, p<0.005), Table 1.

Conclusion:
The difference between AI ECG and chronological age is an independent predictor of all-cause mortality in ACHD patients.
Abstract 4147535: Cryptogenic stroke and Patent Foramen Ovale: Elevated Lipoprotein (a), a factor in the equation
Authors: Rodriguez-Taveras Joan , Reyes Herrera Danna , Garcia Diaz Bradly , Araujo Alejandro , Suero Claudia , Castillo de la Cruz Gabriella , Fondeur Acosta Juan , Santiago Javier , Perez Colome Ernesto , Guzman Christian , Romano Peralta Ramón , Herrera Baez Karla , Urena Neme Ana Paula , Tarafa Jorge A. , Ureña Velasquez Pedro Enrique
Published: November 2024

Background:
Despite the association between cryptogenic stroke and patent foramen ovale (PFO), data on the efficacy of PFO closure for secondary prevention remains limited. Guidelines recommend PFO closure only for patients with a prior stroke. As recent studies indicate a correlation between elevated Lipoprotein(a) levels and stroke, its measure could be relevant in evaluating the need for PFO closure.

Aims/Hypothesis:
This study aims to determine if elevated Lipoprotein (a) levels in patients with PFO increase the likelihood of stroke or transient ischemic attack (TIA). We hypothesize that elevated Lp(a) levels, given their known association with cryptogenic stroke, should be considered when evaluating patients for PFO closure.

Methods:
Case-control study on patients with PFO between January 2018 to April 2024. Patients with previous TIA or evidence of a prior stroke on CT/MRI were classified as “Stroke Group”. An Lp(a) level ≤ 30mg/dL was considered normal. Multivariate logistic regression was used to analyze the impact of age, gender, hypertension, diabetes, smoking status, coronary artery disease, hypothyroidism, dyslipidemia, and LP(a) levels on developing stroke or TIA.

Results:
A total of 96 patients were included (Stroke group=55; Control group=45). Significant differences were found between groups in age [46.38±11.06 vs 44.42±13.01; p=0.02], BMI [27.75(4.8) vs 25.34(4.8); p=0.02], hypertension [43.6% vs 17.1%; p<0.01], and migraine [27.3% vs 7.3%; p<0.01]. Elevated Lp(a)was more prevalent in the Stroke Group [60% vs 39.02%; p=0.04]. No significant differences were observed in LDL [94.80±33.95 vs 108.84±28.92; p=0.669], HDL (54.77±13.63 vs 63.89±15.16; p=0.205), Non-HDL (132.35±47.88 vs 156.23±38.86; p=0.651), and HbA1c [5.5%(0.35) vs 5.3%(0.30); p=0.143]. The logistic regression model revealed that besides the difference in baseline characteristics, only dyslipidemia (OR=4.02, 95% CI:1.145–14.125, p<0.002), migraine (OR=4.02, 95% CI:1.145–14.13, p<0.03), and elevated Lp(a) (OR=8.68, 95% CI: 2.15–35.02, p<0.002) were significantly associated with increased odds of TIA/Stroke.

Conclusion:
In patients with PFO, elevated LP(a) increases the odds of developing cerebrovascular events. Measure of Lp(a) should be included in the evaluation for PFO closure.
Abstract 4147551: Comparison of HFpEF Cardiac Output Augmenters versus Non-Augmenters during Exercise Right Heart Catheterization
Authors: Tanacli Radu , Tajdini Masih , Jani Vivek , Hahn Virginia , Sharma Kavita
Published: November 2024

Introduction:
Exercise intolerance is a hallmark feature of heart failure with preserved ejection fraction (HFpEF), resulting in reduced quality of life. We report here several characteristics associated with a incomplete cardiac index (CI) augmentation during supine bicycle exercise RHC in patients with HFpEF.

Methods:
We evaluated 67 patients with HFpEF and RHC exercise stress testing from the Johns Hopkins Heart Failure with Preserved Ejection Fraction Clinic. Histopathologic examination for cardiomyocyte hypertrophy, interstitial fibrosis, and inflammatory infiltrate was available 56 patients with RHC endomyocardial biopsy (EMB). Demographic, clinical, echocardiography, blood tests and pulmonary function tests (PFTs) were included in the analysis.

Results:
We found that 60 of 67 (90%) of HFpEF patients improved their baseline CI during exercise, with a mean percent increase between baseline and maximal exercise stage of 53.5±41.6 %. The mean stage of exercise attained was 3.1±1.7 with mean energy of 26.0±17.8 watts. We further divided the patients in 2 groups: patients with ≥50% CI increase at maximal effort (HFpEF-augmenters) and, those with < 50% CI increase (HFpEF-non augmenters). HFpEF-augmenters achieved higher exercise stage, higher maximal HR and maximal SV. Of the HFpEF-augmenters, 23 (74%) saw an increase in both SV and HR; 6 (19%) increase in SV only, 2 (6%) increase in HR only. Of the HFpEF-non-augmenters, only 15 (42%) had an increase in both SV and HR, 14 (39%) had an increase in HR but decline in SV and 8 (22%) had an increase in SV but a decline in HR (
Figure
). Presence of comorbidities and NYHA class distribution were similar between the 2 subgroups. HFpEF-non augmenters had higher log NT-proBNP, hepatic enzymes, uric acid and cystatin C, lower cholesterol, higher pulmonary vascular resistance and lower PFTs (total lung capacity, forced vital capacity and FEV1) than HFpEF-augmenters (
Table
). Degrees of hypertrophy, fibrosis and inflammation on EMB did not differ between groups.

Conclusion:
In an obese HFpEF cohort with exercise hemodynamic testing those unable to augment cardiac index had a variable degree of chronotropic and inotropic/lusitropic incompetence, higher log NT-proBNP, elevated markers of hepatic and renal impairment, lower cholesterol and lower PFTs.
Abstract 4147581: Survival Prediction after Cardiac Resynchronization Therapy: Clinical Scores versus Ejection Fraction
Authors: Demian Joe , Paul Aritra , Varma Niraj , Finet J. Emanuel , Kochar Arshneel , Bader Feras , Wazni Oussama , Tang Wilson , Rickard John
Published: November 2024

Background:
Left Ventricle Ejection Fraction (LVEF) has been a key predictor of long-term patient outcomes post-CRT. However, clinical scores may offer superior predictive value.

Hypothesis:
We hypothesized that clinical scores assessed at 6 months post-CRT would be better predictors of long-term survival.

Aims:
To compare the predictive accuracy of various clinical and LVEF for 2-year survival in patients who underwent CRT.

Methods:
This prospective cohort study included patients who underwent CRT at the Cleveland Clinic between May 2016 and June 2022. A set of clinical scores and LVEF were assessed at 6 months post-CRT. Our primary endpoint was Event-Free Survival (EFS) – defined by the absence of both significant cardiac interventions (LVAD implantation or heart transplant) and mortality. Scores included 6 Minute Walk Distance (6MWD; <1200ft), Gait Speed (GS, <0.7m/s), Timed Up and Go Test (TUG, >12s), SOF Frailty Index (SOF, ≥2) and the 5-level EuroQol-5 Dimension (EQ-5D-5L, >10). Each parameter was individually incorporated into a base Cox proportional hazards models while adjusting for baseline parameters. The predictive accuracy was compared using the concordance index (C-index).

Results:
Overall, 527 patients were recruited, of which 346 (66%) were men and 422 (81%) received a defibrillator. Median (IQR) values for age, QRS duration, LVEF, and NYHA class were 71 years (IQR: 62-78), 160ms (IQR: 146-176), 29% (IQR: 23-35), and 2 (IQR: 2-3), respectively. The response rate at 6 months post-CRT was 322 (67.9%), and the 2-year EFS rate was 400 (75.9%). Significant predictors of 2-year mortality included 6MWD (HR: 2.8542, p<0.001), GS (HR: 3.2145, p<0.001), TUG (HR: 2.5056, p<0.001), SOF (HR: 2.7371, p<0.001) and EQ-5D-5L (HR: 2.3324, p<0.001), and LVEF was not a significant predictor (HR: 0.9901, p=0.337). C-index values of the clinical scores – 6MWD (0.748), GS (0.746), TUG (0.741), SOF (0.753), EQ-5D-5L (0.730) – proved superior to LVEF (0.719).

Conclusion:
Our findings show that clinical scores are better predictors of two-year EFS following CRT than LVEF. Thus, incorporating functional assessments into post-CRT evaluation may improve survival prediction and patient management.
Abstract 4147594: Improving Pregnancy Outcomes through Remote Monitoring and Rewards for Participation
Authors: Vernon Marlo , Tracy Dustin , Pollard Elinita , Patel Alisha
Published: November 2024

Background:
Mental health issues, preeclampsia, and eclampsia were among the leading causes of pregnancy-related deaths from 2018-2020 in Georgia. Studies from other countries have suggested that self-measured blood pressure (SMBP) among pregnant and postpartum women is a feasible method for reducing the risk for hypertension-related pregnancy complications (e.g., preeclampsia, eclampsia). Long-term risks of CV issues during pregnancy are known to increase the risk of stroke and heart attack later in life. Despite the benefits of SMBP, its impact is understudied among at-risk women during and after pregnancy. Therefore, we aimed to explore if incentives are associated with an increase in blood pressure (BP) reporting among pregnant and postpartum women utilizing the VidaRPM application.

Methods:
91 women (67.5% HS or less, 58.8% Black, Mean Age = 27.01y) were randomized to the control (usual care, n=30), regular (SMBP through VidaRPM, n=30), or incentivized (SMBP with incentives, n=31). All women were between 13 and 34 weeks of pregnancy. All participants received a blood pressure monitor, and online education resources, and were asked to record BP three times a week and one mental health survey a week during pregnancy until the 12
th
week postpartum. Regular SMBP participants received additional education, self-efficacy assessment, and ongoing support. Incentive participants received an additional $25 gift card for full engagement between 34 weeks of pregnancy and 6 weeks postpartum. Women who reported BP outside the normal range were instructed to follow up with their providers.

Results:
Moms in the Control Group had full engagement for 5 out of 304 weeks, regular SMBP arm for 56 out of 245 weeks, and Incentive arm, for 76 out of 254 weeks. The difference among all three groups is statistically significant (p-value = 9.7e-15) however the difference between the two treatment groups is not.

Discussion:
The incentive and regular SMBP groups demonstrated significantly increased adherence to reporting compared to control, and the incentive group more than regular group. This result supports incentivized SMBP during and after pregnancy, possibly reducing missed hypertensive issues and reducing the risk of unmonitored long-term cardiovascular outcomes. Improving women’s self-efficacy and knowledge of risk among at-risk populations will positively impact short and long-term CV health.
Abstract 4147671: Exosomes from Induced Pluripotent Stem Cell-Derived Cardiomyocytes, miRNA, and siRNA Restore the Porcine Chronic Myocardial Injury Model
Authors: Tzng Eileen , Ueyama Tsuyoshi , Inoue Hiroyuki , Koike-Ieki Mariko , Kashipathy Maithri , Sierra Raymond , Vadgama Nirmal , Wakatsuki Soichi , lyins jennifer , Ikeda Gentaro , Yang Phillip
Published: November 2024

Introduction:
Heart failure is the leading cause of hospital admission in the U.S. We previously demonstrated that exosomes (Exo) from induced pluripotent stem cell (iPSC)-derived cardiomyocytes (iCMs) significantly restored murine peri-infarct region. Furthermore, we delineated that miR20/92/363 (CORE miRNA) in Exo activated iCM proliferation and restored the injured myocardium by derepressing the Notch3 pathway. However, the optimal pre-clinical method to target the Notch3 pathway effectively through Exo, miRNA, and siRNA remains to be assessed.

Hypothesis:
Exo are the most effective biologic to target the Notch3 pathway to improve chronic porcine heart failure model by cardiomyocyte proliferation.

Methods:
iPSCs were differentiated into iCMs. Exo were isolated from the iCM culture media. Yorkshire pigs were subjected to ischemia-reperfusion injury via balloon occlusion of the left descending artery for one hour. One month later, chronic heart failure model was developed, and percutaneous catheter system (Biocardia, Inc) delivered 10
11
Exo, 4200 µg of CORE miRNA, or 4200 µg of siNotch3 into the porcine peri-infarct region. MRI and transcriptomic analyses evaluated the function, morphology and genomic changes in the injured porcine myocardium.

Results:
Significant improvement in mean absolute change in LVEF when compared to PBS (control, n=6) was achieved in CORE miRNA (n=5), iCM-Exo (n=5), and siNotch 3 (n=4) treatments: 5.89 ± 1.53***, 7.07 ±3.59***, and 4.73 ± 3.17** respectively (PBS -3.55 ± 3.27, mean±SD, **p<0.01, ***p<0.001). LV end systolic volume was significantly reduced in both CORE miRNA and iCM-Exo treatment groups. Transcriptomic analysis of the porcine myocardium was performed to assess cell proliferation and metabolism.

Conclusion:
All biologics were effective in repairing the porcine myocardium after chronic myocardial injury. iCM-Exo showed the highest functional restoration. Dose-response study is ongoing to optimize the restorative effects.
Abstract 4147677: Exercise Pulmonary Vascular Resistance relates to impaired RV-PA coupling and effort intolerance in HFpEF
Authors: Tanacli Radu , Jani Vivek , Tajdini Masih , Hahn Virginia , Sharma Kavita
Published: November 2024

Introduction:
Elevated pulmonary vascular resistance (PVR) during exercise is a proposed marker of negative prognosis in patients with heart failure with preserved ejection fraction (HFpEF), however its pathophysiology is incompletely characterised. We investigate here the relative contribution to exercise-induced PVR on right ventricular (RV) functional and structural remodelling and pulmonary artery (PA) coupling during exercise in HFpEF patients.

Methods:
We included 67 consecutive patients from the Johns Hopkins HFpEF Clinic where supine bicycle exercise right heart catheterisation (RHC) was available. In agreement with previous studies, we defined 2 distinct subgroups: patients with elevated exercise-induced PVR (HFpEF-highPVR), including patients with PVR ≥ 1.74 WU at maximal effort and those without exercise-induced PVR (HFpEF-normalPVR) patients with PVR < 1.74 WU at maximal effort. Echocardiography and RV endomyocardial biopsy (EMB) data were analysed to assess cardiac structural and functional remodelling associated with HFpEF-highPVR.

Results:
From the total of 67 patients, 23 (34%) had elevated PVR at rest (PVR≥2 WU) of which 17 (74%) continued on to have exercise-induced PVR (PVR≥1.74 WU). From 44 (66%) patients without elevated PVR at rest, 4 (9.1%) further developed PVR at maximal exercise. (
Figure1A
). HFpEF-highPVR were older, had lower eGFR and higher NT-proBNP, than HFpEF-normalPVR. Maximal exercise tolerance was severely reduced in the HFpEF-highPVR group (14.0±13.7 vs 31.4±16.9 watts, P<0.001;
Figure 1B
). HFpEF-highPVR was associated with lower PA compliance (2.7±1.0 vs 5.2±1.7 mL/mmHg, P<0.001), higher PA elastance (840±320 vs 441±138 mmHg/mL, P<0.001) and higher diastolic pulmonary gradient (4.71±4.23 vs 2.07±2.69 mmHg, P=0.014). Patients with HFpEF-highPVR had a higher frequency of RV dilatation (OR=5.42, 95%CI 1.36-21.70, P=0.012), LV restrictive diastolic filling (OR=3.80, 95%CI 1.08-13.37, P=0.031) by echocardiography, and, higher frequency of moderate and severe hypertrophy (OR=4.80, 95%CI 1.48-15.61, P=0.007) and presence of fibrosis (OR=4.71, 95%CI 1.18-18.80, P=0.021) on EMB.

Conclusion:
Patients with elevated PVR during exercise had more pronounced maladaptive RV remodelling and less compliant PA, which contributed to impaired hemodynamic and lower endurance. Assessing exercise PVR can offer an important distinct insight into HFpEF phenotype classification and further stratify clinical risk.
Abstract 4147679: CD39 Expression on Tregs Associates with the Severity of Atherosclerosis in Mice and Humans: Impact on Efferocytosis.
Authors: Watson Samuel , Detrick Lauren , DHerete Eli , Bermeo-Blanco Oscar , Robson Simon , Covarrubias Roman , Gumina Richard
Published: November 2024

Objective:
Atherosclerosis is a chronic inflammatory condition. Extracellular nucleotide metabolism by CD39, encoded by the ENTPD1 gene, plays a role in modulating inflammation. Our objective of this study was to elucidate the molecular and inflammatory mechanisms by which CD39 activity modulates atherosclerosis

Approach and Results:
Here we identify that the genotype of SNP rs3814159 in the promoter region of the ENTPD1 gene strongly associates with the level of expression of Tregs (p<0.001; GG=Treg CD39low; AA=Treg CD39high). Given the contribution of Tregs to regulating inflammation and atherosclerotic cardiovascular disease, we examined the extent of angiographic atherosclerosis using a 17-segment modified AHA model (Gensini Score) in 85 consecutive patients referred for coronary angiogram. Analysis of atherosclerotic burden by rs3814159 genotype demonstrated a significantly higher burden of disease in those patients with the GG (Treg CD39low) genotype (Fig. 1A: p=0.0373). To study how differences in CD39 activity in Tregs affect atherosclerosis. We generated a cre-lox Treg cell-specific CD39 knockout mouse model with green fluorescent protein (GFP) labeled FoxP3 (FoxP3-Cre GFP+ CD39flox) and crossed this into an Ldlr-/- background. We fed high-fat diet (21% saturated fat, 0.15% cholesterol) to Ldlr-/--FoxP3-Cre+-Cd39wt/wt (Treg Cd39high) and Ldlr-/-- FoxP3-Cre+-Cd39flox/flox (Treg Cd39low) mice for 16 weeks. Examination of the aortic sinus by Oil Red O-stained cross-sections revealed a significantly increased lesion area in Treg Cd39low mice (Fig. 1B: p= 0.0321). Next, using an established model of zymosan-induced peritonitis, macrophage efferocytosis of irradiated splenocytes was examined in vivo. Peritoneal macrophages from Treg Cd39low demonstrated a significant reduction in efferocytosis compared to Treg Cd39high mice (Fig. 1C: p=0.047).

Conclusion:
Our data support that a reduced expression of CD39 on Tregs results in increased atherosclerosis burden in humans and mice. The mechanism appears to involve Treg regulation of macrophage efferocytosis.
Abstract 4147717: Sodium Glucose Cotransporter 2 Inhibitors on Chronic Heart Failure with Reduced Ejection Fraction in Adult Congenital Heart Disease Patients: A Systematic Review and Meta-analysis
Authors: Das Bibhuti , Niu Jianli
Published: November 2024

Background:
SGLT2 inhibitors have demonstrated efficacy in reducing cardiovascular death and hospitalization and are recommended as first-line therapy for hear failure (HF) in adults due to acquired heart diseases. Our study aimed to assess the safety, tolerability, and outcomes of HF patients with adult congenital heart disease (ACHD) treated with SGLT2 inhibitors.

Methods:
We conducted a comprehensive search of three major databases—PubMed, Scopus, and Embase—and collected articles on the use of SGLT2 inhibitors for HF in ACHD patients who were already receiving angiotensin-converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARB), angiotensin receptor neprilysin inhibitors (ARNI), beta-blockers (BB), and mineralocorticoid antagonists (MRA). We excluded articles related to acute decompensated HF and HF with preserved ejection fraction. The primary outcome was the change in NYHA functional class (FC). Secondary outcomes included changes in B-type natriuretic peptide (BNP) and N-terminal pro-BNP (NT-proBNP) levels, as well as body weight. Additionally, we evaluated the safety and tolerability of SGLT2 inhibitors in ACHD HF patients. A pooled effect size was calculated based on mean differences (MD) or log odds ratio (LogOR).

Results:
Our meta-analysis included 9 studies with a total of 287 patients aged 19 to 67 (median 37.5 years) (Table). When SGLT2 inhibitors were added to combined therapies, they significantly improved NYHA FC (LogOR: 1.3, 95% CI: 0.37–2.23, p=0.01) (Figure 1A), decreased NT-proBNP (MD -0.43, 95% CI -0.70 to -0.16, p=0.00) (Figure 1B), were associated with a reduction in systolic blood pressure (MD = -0.32, 95% CI: -0.51 to 0.14, p=0.00) (Figure 1C), and led to an elevation of creatinine (Cr) levels (MD = 0.18, 95% CI -0.0 to 0.36, p=0.06) (Figure 1D). Only 4 patients experienced urinary tract infections (UTIs), and none had hypoglycemia or ketoacidosis.

Conclusion:
Our meta-analysis demonstrates that SGLT2 inhibitors improve NYHA FC, decrease NT-proBNP, and are well-tolerated with safety features similar to adult HF clinical trials when added to combination HF therapies including ACEI/ARB/ARNI, BB and MRA. Future prospective studies are needed to assess long-term clinical outcomes in ACHD patients with HF.
Abstract 4147720: Dual Inhibition of Glutaminolysis and Pyruvate Carboxylase Attenuates Pulmonary Arterial Hypertension
Authors: Valuparampil Varghese Mathews , James Joel , Bharti Dinesh , Niihori Maki , Rafikova Olga , Rafikov Ruslan
Published: November 2024

Introduction:
Pulmonary arterial hypertension (PAH) is a serious condition that impacts the lung vasculature and has diverse underlying factors. Previous research has shown that mitochondrial dysfunction (MD) significantly contributes to PAH; however, the mechanisms remain unclear. Our recent findings indicate that in PAH, anaplerosis enhances the TCA cycle in pulmonary vascular cells, compensating for MD.

Hypothesis:
We hypothesize that inhibiting anaplerosis by targeting pyruvate carboxylase (PC) and glutaminolysis (GLUD1) in early PAH can prevent metabolic changes and pulmonary vascular remodeling.

Methods:
PAH was induced in female SD rats using Sugen/Hypoxia (Su/Hx). Anaplerosis inhibitors-phenylacetic acid (PAA), a PC inhibitor, at 20 mg/kg every other day (i.p.), and R162, a GLUD1 inhibitor, at 30 mg/kg daily (i.p.) were initiated after the right ventricular systolic pressure (RVSP) reached above 70 mmHg at week-two and continued for three weeks.

Results:
Hemodynamics in Su/Hx showed a PAH phenotype with increased RVSP. However, inhibiting anaplerosis reduced RVSP (111.10±3.59 mmHg to 45.87±2.202 mmHg, p<0.001), Fulton Index (0.59±0.017 to 0.45±0.024, p<0.001), and myocardial contractility (Max dP/dt 4511±196.9 mmHg/s to 2403.63±123.7 mmHg/s, p<0.001). Our PAH model showed increased glycolytic flux with the activation of HK1 (p<0.001) and PKM1 (p<0.05). Increased glycolysis was found to shift to the pentose phosphate pathway via myo-inositol oxygenase (p<0.001), generating ROS in the early PAH model. This leads to mitochondrial dysfunction with a reduction in complex-II (p<0.05) expression and activation in the glycerophosphate shuttle with increased GPD2 (p<0.001). These mitochondrial and redox imbalances trigger the endo-mesenchymal transition, leading to vascular remodeling in the late PAH model. Furthermore, the increased proliferative demand shifts the metabolism towards anabolism with NTX1 activation (p<0.05), leading to proliferative signaling such as Akt (p<0.01) and STAT3 (p<0.05). Remarkably, inhibiting anaplerotic pathways with combined PAA and R162 therapy in the Su/Hx PAH model significantly attenuated metabolic dysfunction and prevented proliferative signaling, thus averting lung vascular remodeling.

Conclusion:
Our research indicates that inhibiting both pyruvate carboxylase and glutaminolysis-driven anaplerosis is a promising therapeutic approach for addressing vascular remodeling in PAH.
Abstract 4147724: Effect of Nicorandil Therapy on Infarct Size in ST-Segment-Elevation Myocardial Infarction: A Systematic Review and Meta Analysis of Randomized Controlled Trials
Authors: Hayat Malik Saad , Rehman Obaid Ur , Chaudhary Ahmed , Shaukat Muhammad Talha , Shoaib Muhammad Mukarram , Naseer Rayyan , Rehman Wania , Ahmad Hadia , Shoaib Muhammad Mohtasham , Rehman Aqeeb Ur , Mohsin Aleenah , Qureshi Muhammad Ahmad
Published: November 2024

Background:
ST-Elevation Myocardial Infarction (STEMI) has a huge clinical burden globally. Pre-administration of Nicorandil before primary percutaneous coronary intervention for STEMI has demonstrated efficacy in enhancing microvascular recovery and reducing reperfusion injury in RCTs. Consequently, Nicorandil exhibits potential in providing considerable cardioprotective advantage in STEMI patients.

Aims:
Nicorandil therapy is being extensively investigated as a treatment for reperfusion injury associated with primary percutaneous coronary intervention. This meta-analysis evaluates various studies to determine the cardioprotective effects of nicorandil, with particular emphasis on its influence on infarct size.

Methods:
MEDLINE (via PubMed), Scopus, Cochrane Library, and Google Scholar were systematically searched for relevant studies. Primary endpoint was infarct size. Left Ventricular End Diastolic volume, Left Ventricular End Systolic Volume, Left Ventricular Ejection Fraction (LVEF), Major Adverse Cardiovascular Events (MACE), and rehospitalizations were analysed as secondary end points. Review Manager 5.4 was used to pool mean differences (MD) and Risk Ratios (RR) along with their 95% Confidence Intervals (CI).

Results:
3 RCTs including a total of 438 patients were included in our review. Compared with placebo, nicorandil therapy significantly reduced infarct size with a pooled MD of -3.20 (95% CI -5.25 to -1.14). There was also significant reduction in Left Ventricular End Systolic Volume (MD= -5.63; 95% CI -11.22 to -0.05) and a nonsignificant reduction in Left Ventricular End Diastolic Volume (MD= -6.37; 95% CI -12.74 to 0.01). Nicorandil therapy caused a nonsignificant decrease in MACE (RR=0.74; 95% CI 0.37 to 1.46) and readmission rate (RR=0.73; 95% CI 0.30 to 1.77) compared to placebo. It also caused a significant increase in the Left Ventricular Ejection Fraction (LVEF) with a pooled MD of 2.53 (95% CI 0.53-4.54).

Conclusion:
Pre-treatment with Nicorandil in STEMI patients being treated with primary percutaneous coronary intervention is associated with significant improvement in infarct size and cardiac systolic function.
Abstract 4147751: Outcomes of Concomitant Longitudinal Sleeve Gastrectomy and Mechanical Circulatory Support in Patients with Morbid Obesity
Authors: Bhardwaj Anju , Annigeri Sanjay , Gehring R , Kumar Sachin , Nathan Sriram , Radovancevic Rajko , Kar Biswajit , Gregoric Igor
Published: November 2024

Introduction/Background:
Obesity and heart failure often co-exist as either a cause or effect of one another. Patients with morbid obesity have few options in terms of definitive therapies to treat heart failure. There is limited outcome data on patients with obesity and left ventricular assist devices (LVADs). Our institution has used a concomitant procedure that implants a gastric sleeve at the same time as an LVAD.

Research Question/Hypothesis:
We hypothesize that the concomitant procedure enables subjects to attain transplant eligibility while limiting complications.

Goals/Aims:
Analyze institutional data to identify baseline outcome statistics for the concomitant procedure.

Methods/Approach:
We retrospectively reviewed records from patients with morbid obesity (body mass index > 35 kg/m
2
) who underwent concomitant longitudinal sleeve gastrectomy (LSG) and LVAD implantation between November 2013 and March 2022. A minimum of 2 years of follow-up data was collected. The primary endpoint was transplant listing or LVAD explantation. Secondary outcomes included mortality and related complication rates.

Results/Data:
A total of 56 patients were included for analysis. The concomitant LSG and LVAD procedure has enabled 82.1% (46/56) of patients to reduce their BMI to below 35 kg/m
2
. Overall, 60.7% (34/56) of subjects met the primary endpoint; the median number of days to listing or explantation was 401. Thirty-two patients were listed for transplant, and 17 have been successfully transplanted. Two patients demonstrated recovery and underwent successful explant of the LVAD and remained New York Heart Association Class II at follow-up. Six subjects died before receiving a transplant, with two being listed at the time of death (Figure). Complications were noted, but they do not seem to limit the ultimate goal of transplantation.

Conclusions:
A significant portion of patients who were ineligible for heart transplantation were able to reduce their BMI and become eligible. The incidence of complications for this concomitant procedure is low. Multicenter studies are needed to establish this approach as a standard of care for patients with morbid obesity and stage D heart failure.
Abstract 4147769: Outcomes of Elevated Homocysteine in Heart Failure Hospitalizations. A Propensity Matched Retrospective Analysis
Authors: Evbayekha Endurance , Nelson Favour , Okorare Ovie , Palumbo Rachel , Ebong Imoh , Shamaki Garba Rimamskep , Bob-Manuel Tamunoinemi
Published: November 2024

Introduction:
Elevated homocysteine (HC) predisposes individuals to a prothrombotic state and may increase the risk of poor outcomes, including strokes and deep venous thrombosis (DVT). Previous studies did not find any mortality benefit after normalizing serum homocysteine levels. However, studies on the impact of HC on outcomes such as peripheral vascular disease (PVD) and chronic limb ischemia (CLI) in heart failure (HF) are lacking. We aimed to address this gap.

Methods:
We examined the 2016 to 2021 Nationwide Inpatient Sample database and used the ICD-10 codes to identify the population with HF. We then stratified them into HC and non-HC groups. HC was defined as a composite of homocystinuria and methyltetrahydrofolate deficiency. Chi-square and Student T-test were used to compare continuous and categorical variables. A greedy neighbor 1:1 propensity score matching (PSM) followed by multivariable logistic regression models accounted for confounders and predicted the outcomes. Our primary outcomes were PVD and CLI, while secondary outcomes were ischemic stroke, pulmonary embolism (PE), and DVT.

Results:
There were 3,415 HF hospitalizations with HC, with a mean age of 66.6 + 14.8, and 55.9% (1,910) were females.

After PSM, 1,420 HC hospitalizations were matched to 1,420 no-HC hospitalizations.

Compared to the non-HC group, there was no difference in PVD 1.15 (0.96-1.37) and CLI 0.66 (0.28-1.51), each p> 0.05.

However, ischemic stroke 3.3 (2.30-4.69), PE 6.3 (3.46-11.51), and DVT 3.6 (2.26-5.8) were significantly associated with the HC group, p<0.005, each.

Conclusions:
Among the hospitalized population with heart failure, those with elevated homocysteine showed a higher association with ischemic stroke, DVT, and PE but no difference in peripheral vascular disease or chronic limb ischemia.