bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 4114198: Humanin Level is Inversely Correlated with NT-proBNP Level and Mortality in Heart Failure with Reduced Ejection Fraction
Authors: Yan Crystal , Grazette Luanda
Published: November 2024

Background:
Mitochondrial dysfunction contributes to heart failure (HF) progression via diminished energy supply, release of reactive oxygen species, and increased cell death. However, there has yet to be clinically relevant biomarkers that address mitochondrial-mediated cardiac injury in patients. Humanin (HN) is a mitochondria-derived peptide that protects cells through the interference of apoptosis and reduction of oxidative stress. The objectives of our study were to measure circulating plasma HN levels in patients with HF with reduced ejection fraction and describe the relationship of HN to validated, clinically relevant measures of HF.

Methods:
We conducted a prospective cohort study. To be included in the study, patients must have: 1) left ventricular ejection fraction <40%, 2) high risk of future clinical instability, 3) medication and device treatment according to guidelines, and 4) stable medical therapy for at least 30 days prior to screening. Plasma HN levels were measured at time of study enrollment by an enzyme-linked immunoassay. Statistical analyses were performed to evaluate the relationships between HN levels and demographic variables, quantitative measures of HF, and clinical outcomes.

Results:
54 HF patients were included in the study. Age and sex were not significantly associated with HN level. There was a significant difference in mean HN level by race with highest HN level seen in Caucasians and the lowest HN level seen in Hispanics (1310 pg/ml vs. 630 pg/ml, p=0.012). There was a significant inverse correlation between NT-proBNP level and HN level (r=-0.46, p <0.001). After adjusting for race, higher NT-proBNP level, as both a continuous and categorical variable, was significantly associated with lower HN level. Furthermore, HN level was significantly lower in patients who died within 6 months compared to those who did not (520.7 pg/ml vs. 1146.9 pg/ml, p=0.013). After adjusting for race, lower HN level was significantly associated with increased odds of 6-month mortality (OR=0.784, 95% CI 0.620-0.943, p=0.018).

Conclusions:
To the best of our knowledge, this is the first study to describe plasma HN levels in HF patients. Its significant correlation with mortality and NT-proBNP level supports a potential role for HN as a novel prognostic biomarker in HF with reduced ejection fraction.
Abstract 4114372: Is Takotsubo syndrome associated with a favorable in-hospital outcome among patients with cardiogenic shock? A propensity score-matched analysis of the National Inpatient Sample Data (2016-2020)
Authors: Siraw Bekure , Nguyen Hong Thoai , Paudel Hemraj , Yasmeen Juveriya , Hussein Mohammed , Medina-Inojosa Jose , Hussein Khalid , Somarouthu Kirthi , Bastola Satish
Published: November 2024

Background:
Takotsubo cardiomyopathy (TTC) is characterized by impaired left ventricular function due to typical, regional wall motion abnormalities in the absence of significant obstructive coronary artery disease. Previous small-sized retrospective studies reported favorable outcomes of cardiogenic shock in patients with TTC. We aimed to investigate whether the presence of TTC is associated with a favorable in-hospital outcome among patients admitted for cardiogenic shock using a large nationally representative dataset.

Methods:
Utilizing data from the National Inpatient Sample (NIS) spanning from 2016 to 2020, we identified patients admitted for cardiogenic shock using ICD-10 codes. Patients with TTC were also identified using ICD-10 codes. Using sociodemographic variables, and comorbid medical conditions, and performed procedures as matching variables, we conducted a 1:1 nearest-neighbor propensity score matching to mitigate potential confounders. The success of matching was evaluated based on standardized mean differences. In-hospital mortality was the primary outcome, while in-hospital complications, length of stay (LOS), and cost of hospitalization were secondary outcomes. We employed the Cochrane-Mantel-Haenszel method to assess the odds ratio (OR) for in-hospital mortality and complications. Simple linear regression models were used to evaluate differences in LOS and cost of hospitalization.

Results:
The final sample included 22,594 patients, evenly distributed between the groups with and without TTC. The mean age of the cohort was 65.4 years (SD = 15.9), with 74.7% being males. Ethnic composition indicated 75.7% Whites, 9.3% Blacks, and 8.1% Hispanics. The overall in-hospital mortality rate was 32.7%. The TTS group had a lower mortality rate (38.4% Vs 27%, p<0.001). Patients with TTC had lower odds of in-hospital mortality, cardiac arrest, ventricular tachycardia, and acute kidney injury. However, they were noted to have higher odds of deep vein thrombosis, stroke, slightly higher LOS, and cost of hospitalization.

Conclusion:
In summary, our study suggests that Takotsubo Cardiomyopathy is associated with significantly lower in-hospital mortality rates among patients admitted for cardiogenic shock, indicating a favorable prognosis in this clinical setting.
Abstract 4114461: Low-density lipoprotein cholesterol, prevalence of cardiovascular disease risk factors, and predicted cardiovascular disease risk among young adults: National Health and Nutrition Examination Survey 2015-2020
Authors: Zheutlin Alexander , Luebbe Samuel , Stulberg Eric , Chaitoff Alexander
Published: November 2024

Introduction:
It is unclear if young adults with hyperlipidemia are also more likely to have non-lipid cardiovascular disease (CVD) risk-factors or higher long-term CVD risk. As such, we assessed associations between low-density lipoprotein cholesterol (LDL-C) levels and non-lipid CVD risk factors as well as 10- and 30-year risk of CVD in young adults.

Methods:
We included a nationally representative sample of adults 20-<40 years from the National Health and Nutrition Examination Survey (January 2015-March 2020). We described sociodemographic characteristics and CVD risk factors by LDL-C level. We used simple logistic regression to determine associations between LDL-C level and each CVD risk factor. We then calculated the median 10- and 30-year CVD risk by LDL-C category for each participant using the PREVENT risk estimating equations.

Results:
Among 2,133 (weighted estimation: 90.3 million) young adults, 51.0%, 32.6%, 12.5%, and 3.9% had an LDL-C <100 mg/dL, 100-<130 mg/dL, 130-<160 mg/dL, and 160-<190 mg/dL, respectively. Compared to participants with an LDL-C <100mg/dL, those with an LDL-C 100-<130 mg/dL, 130-<160 mg/dL, and 160-189 mg/dL were more likely to have metabolic syndrome, an enlarged waist, hypertension, elevated glucose, diabetes mellitus, high triglycerides, and high hs-CRP (Table). The median 10-year risk of CVD was approximately 1% across all baseline LDL-C levels. Over a 30-year time horizon, the median risk of incident CVD exceeded 5% only in the 130-<160mg/dL and 160-189mg/dL LDL-C categories (6.0% and 7.6%, respectively). LDL-C and the interaction between LDL-C and CVD risk enhancing factors were independently associated with 30-year predicted risk of CVD (p=0.006 and p=0.005, respectively).

Discussion:
Many young adults with an elevated LDL-C have concomitant high-risk CVD characteristics. The risk/benefit calculous for addressing this modifiable risk factor in these patients should be further explored.
Abstract 4114694: A Large Animal Model of Persistent Atrial Fibrillation
Authors: Mostafizi Pouria , Lefkowitz Eli , Ref Jacob , Daugherty Sherry , Grijalva Adrian , Cook Kyle Eric , Chinyere Ike , Lancaster Jordan , Koevary Jen , Goldman Steven , Moukabary Talal
Published: November 2024

Purpose:
Persistent atrial fibrillation (AFib), the most common sustained cardiac arrhythmia in the United States, poses substantial health hazards, such as the formation of blood clots, stroke, and heart failure. Despite available therapies such as ablation and antiarrhythmic drugs, there still is no definitive cure for AFib. Our study aims to bridge this gap by investigating the genetic and molecular factors underlying AFib through the development of an AFib model using Yucatan mini swine as the medium that closely mimics human cardiac physiology.

Methods:
We selected Yucátan mini swine as animal models because they closely resemble humans physiologically and are of a convenient size for performing extended experiments. We surgically implanted pacing leads, implantable cardiac monitors (ICMs), and pacing generators into the swine, along with external Fitbark 2.0 Collars to use activity levels as a measurement of quality of life. After the procedures the swine underwent rapid atrial pacing with the intention to induce persistent atrial fibrillation.

Findings:
An electrocardiogram (ECG) showed that the method of stimulating the right atrium of the heart induced persistent atrial fibrillation in pigs and decreased levels of activity, indicating a decline in their general health. This continued for >7 days after atrial pacing was terminated. Overcoming challenges associated with animal dimensions and model design, we devised specific surgical techniques, including jugular cut-down, lateral cervical implantation coupled with antibiotic support, long sheaths, and customized styluses. These innovations were instrumental in achieving a successful AFib model and overcoming anatomical obstacles.

Summary:
Our study demonstrates the feasibility of creating a large animal model of AFib using Yucatan mini swine. This model closely resembles the clinical presentation of human AFib and could provide valuable insights into the disease mechanism and potential therapeutic strategies. Animal heart and vascular dimensions were the most challenging surgically.
Abstract 4115027: Transcutaneous phototherapy improves left ventricular systolic function
Authors: Kneller James , Nuttall Joe
Published: November 2024

Background:
The emerging field of cardiac optogenetics uses pulses of light to stimulate optically-sensitive proteins in the heart, influencing cellular physiology with unprecedented spatiotemporal resolution. Potential benefits may include heart rhythm stabilization and relief from congestive heart failure (CHF). Transcutaneous phototherapy devices (LifeWave Inc, San Diego, USA) may provide similar benefit without the need for opsin expression in the heart or exogenous light sources.

Objective:
To investigate whether upregulation of carnosine activity using a wearable cutaneous phototherapy device may improve echocardiographic measures of left ventricular systolic function.

Methods:
The Carnosine
®
adhesive skin patch (34 mm diameter) contain an organic crystalline material that reflects specific frequencies of infra-red light emitted through the skin, and known to activate carnosine dipeptides throughout the body. These function as a high-energy phosphate system known to enhance muscle function. Study participants (n=12 healthy volunteers, 40-66 years of age) underwent a focused baseline echocardiogram, which included atrial (A) and early (E) mitral valve inflow, peak tissue velocity (E’) at both the lateral and septal mitral annulus, and left ventricular ejection fraction (LVEF). 10-12 patches were then applied along the sternum and across the left thorax (3
rd
-5
th
interspace), incorporating the anterior axilla. The echocardiogram was repeated after 20-30 minutes.

Results:
LVEF was improved following application of the phototherapy device, increasing from 59.4±5.8% to 66.65±5.8% (Δ 6.3%, p<0.05), predicting an improvement in overall cardiac function. In those with normal diastolic function at baseline, septal E’ increased 7.3±0.57 cm/s to 8.2±0.58 cm/s (Δ 0.87 cm/s, p<0.05), indicating a direct effect on contractility. E and A wave velocities increased 2.46±0.14 cm/s and by 5.7±0.72 cm/s, indicating augmented hemodynamics trending towards significance.

Conclusion:
Cutaneous phototherapy devices may enhance left ventricular systolic function without the need for drug delivery, gene manipulation, or exogenous light sources.
Abstract 4115542: Female patients with Andersen-Tawil Syndrome are more prone to develop cardiac arrest.
Authors: Garcia Alan , Lemus-Zamora Ricky , Salama Frisbie Richard , Damalapati Sai Sri Venkata Yeshwanth , Kayani Abdul Mueez Alam , Gomez Flores Jorge
Published: November 2024

Background:
Andersen-Tawil Syndrome (ATS) is an autosomal dominant disorder characterized by a triad of dysmorphic features, periodic muscular weakness, and ventricular arrhythmias. We presented a meta-analysis of cardiologic-affected ATS patients.

Objective:
This study sought to compare the characteristic features of ATS according to their gender with a special focus on the cardiologic anomalies.

Methods:
To enable a meta-analysis, we searched literature reviews of reported cases or cohort studies with ATS between 1994 and 2024. Cases were selected if they presented a cardiologic affection alone or combined with morphologic features, periodic paralysis, or both. A gender comparison was made using the available information. Each variable was calculated using the validated percentage. Numerical variables are expressed as mean or median and SD. Categorical variables are expressed as percentages. Student’s t-test was used for numerical variables. Categorical variables were analyzed using chi-square. The results were expressed as an odds ratio (OR) with a 95% confidence interval (CI). Values of p <0.05 were considered statistically significant.

Results:
The studied population consisted of 243 cardiologic-affected patients with ATS, 163 females, and 80 Males. Compared to males, females are less likely to present periodic paralysis (p = 0.03, OR = 0.54, 95% CI = 0.30-0.98). Analyzing cardiologic features, females had more syncope episodes than males (73% (n=52) vs. 22.4% (n=15). Only 45% of cases had a prolonged QTc. A longer QTc measure was reported in females (453 ± 52) compared to males (427 ± 55) (p = 0.004). Premature ventricular contractions (PVCs) were the most commonly reported arrhythmia, and bigeminy was the most common type of presentation. Polymorphic PVCs were more prevalent in females than males (p = 0.009, OR = 2.49, 95%CI = 1.24-4.99). Females reported more Ventricular tachycardias (VT) episodes than males, especially Bidirectional (p = 0.01, OR = 2.10, 95%CI = 1.17-3.78). Thirty-five patients had an episode of cardiac arrest, either non-fatal, fatal or in some cases non-fatal, followed by SCD after years. Females were more prone to develop cardiac arrest compared to males (n=29 vs. n=6, respectively; p = 0.03, OR = 2.66, 95%CI = 1.06-6.72).

Conclusion:
ATS females with cardiologic affection may require a closer follow-up due to the higher risk of developing life-threatening arrhythmias and cardiac arrest than males.
Abstract 4115669: Single-cell and Spatial Transcriptomics Identified Fatty Acid-binding Proteins Controlling Endothelial Glycolytic and Arterial Programming in Pulmonary Hypertension
Authors: Liu Bin , Yi Dan , Li Shuai , Ramirez Karina , Xia Xiaomei , cao yanhong , Dejesus Vinicio , Glembotski Christopher , Dai Zhiyu
Published: November 2024

We are seeking to elucidate the endothelial fatty acid metabolism role for obstructive vascular remodeling in the pathogenesis of PAH.

In this study, we bred a severe mouse model of PH

Egln1
Tie2Cre

mice with

Fabp45
-/-

mice to generate

Egln1
Tie2Cre

/

Fabp45
-/-

mice. We applied single-cell RNA sequencing (scRNA-seq) to profile the pulmonary cells in

Egln1
Tie2Cre

mice and

Egln1
Tie2Cre

/

Fabp45
-/-

mice. Human hPAEC from idiopathic PAH patients and healthy donors were used to measure fatty acid-binding protein 4 and 5 (FABP4 and FABP5) expression via sc-RNA seq and spatial transcriptomics. siRNA-mediated knockdown of FABP4 and FABP5 and lentivirus-mediated FABP4 and 5 overexpression were performed to study cell proliferation, apoptosis, and glycolysis.

Our scRNA-seq analysis demonstrated that both FABP4 and 5 were highly induced in the ECs of

Egln1
Tie2Cre

mice. PAECs from IPAH patients also showed higher expression of FABP4 and 5. Knockdown of FABP4-5 reduced EC proliferation, starvation-induced Caspase 3/7 activity, and glycolysis. Overexpression of FABP4-5 promoted EC glycolysis and proliferation. Genetic deletion of
Fabp4
and 5 in

Egln1
Tie2Cre

mice exhibited a reduction of RVSP, RV hypertrophy, and reduction of EC glycolysis gene programming compared to

Egln1
Tie2Cre

mice.

In conclusion, we found that FABP4 and 5 control EC glycolysis and contribute to the development of PAH.
Abstract 4116148: Seasonal Variation of Unexpected Sudden Cardiac Death
Authors: Mattila Severi M , Latola Hanna , Pakanen Lasse , Hekkanen Jenni , Eskuri Anette , Vahatalo Juha , Ukkola Olavi , Junttila Juhani , Huikuri Heikki , Perkiomaki Juha
Published: November 2024

Introduction:
Data on the occurrence of unexpected sudden cardiac death (SCD) in different seasons are scanty and needs further exploration.

Methods:
Consecutive series of all unexpected SCD victims (n=5,869) who underwent medico-legal autopsy obligated by the Finnish law were prospectively collected from the geographically defined area in the Northern Finland during a twenty years period from 1998 to 2017. The seasonal variation of SCD and its possible causes were assessed in this large SCD victim cohort.

Results:
Unexpected SCD occurred more frequently during the first quarter of a year (from January to March) than during the other quarters (Figure 1). The occurrence of SCD during the twenty years follow-up was 4.5±0.24 during the first quarter of the year per month and 3.9±0.12 during the other quarters of the year per month on average (SCDs during the quarter of a year per month on average per 100,000 inhabitants per year, p<0.001) (Figure 2). The weather was colder during the first quarter of the year (average temperature -9.1 degrees centigrade) than during the other quarters (average temperature +5.7 degrees centigrade). The snow cover was the largest during the first quarter of the year.

Conclusion:
Unexpected SCD occurred more commonly during the first quarter of a year (from January to March) than during the other quarters (from April to December). Cold weather, and perhaps winter-time physical activities in cold environment such as removal of snow, may have contributed to the increased occurrence of SCD during the first quarter of the year.
Abstract 4117414: Risk Factors Associated with Cardiac Hospital Admissions in Cancer Patients Treated with Immune Checkpoint Inhibitors
Authors: Bennetts Joshua , Walker Rhonda , Williams Trent , Sverdlov Aaron , Ngo Doan
Published: November 2024

Background:
Immune checkpoint inhibitors (ICIs) are highly effective anti-cancer treatments for several cancers. However, treatment with ICIs is associated with metabolic perturbations, accelerated atherosclerosis, and increased risks of adverse cardiovascular events. In this study, we aimed to determine risk factors associated with cardiac hospital admissions in patients treated with ICIs for their cancer.

Methods:
Retrospective data was collected for all patients treated with ICIs between 1 January 2010 and 1 January 2020 through the Hunter New England Local Health District (HNELHD), Australia. Patient medical history and demographics were collected through electronic medical records. Outcome data was obtained from the HNELHD Institutional Cardiac and Stroke Outcomes Unit database. Cardiac admission was defined as cardiac disease based on hospital administration
ICD-10
codes. Binary logistic regression was used for multivariate analysis and performed through SPSS version 28.

Results:
A total of 1,080 patients were included in the final analysis. Mean age of patients was 66.9 ± 11.7 years, with the majority male sex (
n
=685; 63.4%). Primary cancer diagnosis of patients treated with ICIs included melanoma (
n
=417; 38.7%), and cancer of the lung (
n
=327; 30.3%). Nivolumab monotherapy was the most used first-line ICI treatment (
n
=475; 44.0%) followed by pembrolizumab monotherapy (
n
=428; 39.6%). A total of 266 (24.6%) patients had at least one cardiac hospital admission. On univariate analysis, pre-existing cardiovascular disease (CVD) (
p
<0.001), diabetes mellitus (
p
<0.001), chronic kidney disease (
p
<0.001), and prior CVD medications (
p
<0.001) were associated with cardiac hospitalisation. On multivariate analysis, prior history of heart failure (
p
<0.001), hypertension (
p
=0.003), ischaemia, and peripheral vascular disease (
p
=0.049) were independently associated with an increased risk of cardiac hospital admission.

Conclusions:
In cancer patients treated with ICIs, pre-existing CVD risk factors increases the risk of cardiac-associated hospitalisations. Adequate CVD risk modification and monitoring during treatment with ICIs may be necessary to reduce cardiac hospitalisations.
Abstract 4117690: Cardiac Rupture as a Life-Threatening Outcome of Takotsubo Syndrome: A Systematic Review.
Authors: Denicolai Martin , Morello Matteo , Del Buono Marco , Sanna Tommaso , Agatiello Carla , Abbate Antonio
Published: November 2024

Background:
Takotsubo syndrome is a reversible cause of heart failure; however, a low percentage of patients can develop serious complications, including cardiac rupture.

Aims:
Analyze case reports or case series of cardiac rupture in patients with Takotsubo syndrome, detailing patient characteristics to uncover risk factors and prognosis for this severe complication.

Methods:
We conducted a systematic search of MEDLINE and Embase databases to identify case reports or case series of patients with Takotsubo syndrome complicated by cardiac rupture, from inception to October 2023.

Results:
We identified 39 reported cases, including 44 subjects (40 females; 4 males) with a median age of 75 (IQR 71-82) years, of White/Caucasian (61%) or East Asian/Japanese (39%) ethnicity. An emotional trigger was present in 15 (34%) subjects and common admission symptoms were chest pain (35 [80%]) and dyspnea (14 [32%]). ST-segment elevation was present in 39 (93%) of 42 cases, with the anterior myocardial segments (37 [88%]) being the most compromised, followed by lateral (26 [62%]) and inferior (14 [33%]) segments. The mean left ventricular ejection fraction was 40±13% and an apical ballooning pattern was observed in all (100%) ventriculographies. The median time to cardiac rupture was 48 (5-120) hours since admission, with the left ventricular free wall (25 [57%]) being the most frequent site of perforation. Surgery treatment was attempted in 16 (36%) cases, and 28 (64%) patients did not survive (Figure).

Conclusions:
Cardiac rupture as a complication of Takotsubo syndrome is a rare clinical condition associated with high mortality. Elderly females, especially from White/Caucasian or East Asian/Japanese descent, presenting with ST-segment elevation in the anterior or lateral leads, and an apical ballooning pattern, are disproportionally affected. Additional studies with prospective collection of patient-level data are needed to better identify those at increased risk for cardiac rupture associated with Takotsubo syndrome and to address ways to improve mortality rates in this population.
Abstract 4117834: Utility of Abdominal Aortic Calcification Assessment for the Prediction of Major Adverse Cardiovascular Events in Liver Transplant Patients
Authors: Cailes Benjamin , Kuitaba Numan , Farouque Omar , Majumdar Avik , Abdelganne Layal , McNamara Shannon , Garrard Nikki , Al-Fiadh Ali , Lancefield Terase , Yudi Matias , Horrigan Mark , Yeoh Julian , Weinberg Laurence , Testro Adam , Sinclair Marie , Lim Ruth , Gow Paul , Koshy Anoop
Published: November 2024

Background:
Cardiovascular disease is a leading cause of postoperative morbidity and mortality following liver transplantation (LT). Presence of abdominal aortic calcification (AAC) has been linked to cardiovascular events in the general population. We investigated whether AAC on pre-transplant computed tomography (CT) predicts major adverse cardiovascular events (MACE) post-LT.

Methods:
Consecutive LT patients between 2010-2018 from the Victorian Liver Transplant Unit (Australia) were included. Extent of AAC was quantified in a blinded fashion, with high AAC defined as a calcium score of ≥500. MACE was defined as any recorded episodes of acute coronary syndrome (ACS), ventricular arrhythmia, decompensated heart failure, or stroke. The primary outcome was post-LT MACE at 30 days and the secondary outcome was all-cause mortality at maximal follow-up.

Results:
Of 461 patients undergoing LT, 350 had suitable CTs for analysis, of which 90 (25.7%) had also undergone CT coronary angiography. High AAC was identified in 98 patients (28.0%). This finding demonstrated a moderate correlation with high coronary artery calcium score (CACS) ≥400 (r=0.52, p<0.001). Fifty-eight MACE occurred in 42 patients (12.0%) within 30-days. High AAC was associated with increased risk of 30-day MACE (OR=2.68 (95%CI 1.39-5.17), p=0.004), and long-term mortality (HR=2.52 (95%CI 1.29-4.92), p=0.007) at a median follow-up of 4.0 years. In addition, high AAC predicted an increased risk of ACS (OR 3.80 (95%CI 1.18-12.27), p=0.025), heart failure (OR 3.07 (95%CI 1.21-7.80), p=0.020) and atrial fibrillation (OR 2.04 (95%CI 1.02-4.07), p=0.048), with a trend to increased prevalence of ventricular arrhythmia (OR 2.67 (95%CI 0.84-8.50), p=0.10). Following multivariate analysis, high AAC remained a strong independent predictor of MACE (OR=3.49, 95%CI 1.21-10.06, p=0.021). Addition of AAC to the revised cardiac risk index (RCRI) improved model fit for predicting MACE (net reclassification improvement of 52.7% (p<0.001)).

Conclusions:
This study demonstrates for the first time that high AAC on routine abdominal CT scans is associated with a 3-fold increased risk of 30-day MACE post-LT, and improves cardiovascular risk prediction compared to traditional risk scores. Quantification of AAC may offer a simple method of improving cardiovascular risk assessment and implementation of preventative strategies in liver transplant patients, using pre-existing scans without additional cost or patient risk.
Abstract 4118018: Increased Risk of Post-Transplant Malignancy After Isolated Heart Transplant in Adult Patients with Congenital Heart Disease
Authors: Leiva Orly , Golob Stephanie , reyentovich alex , Alvarez-Cardona Jose , Bloom Michelle , Halpern Dan , Small Adam
Published: November 2024

Introduction:
Patients with congenital heart disease (CHD) are at increased risk of cancer. In patients with CHD and advanced heart failure, isolated heart transplantation (HT) can be considered. In the overall HT population, immunosuppression after HT increases the risk of post-transplant malignancy (PTM). However, cancer outcomes among adult HT patients with CHD have not been investigated.

Methods:
Patients aged ≥ 18 years who received HT between January 1, 2010 and December 31, 2021 were identified using the United Network for Organ Sharing (UNOS) registry. Patients with CHD were compared to those without. Outcomes were PTM and hematologic malignancy (either leukemia, lymphoma or post-transplant lymphoproliferative disorder). Multivariable Fine-Gray competing-risk regression adjusting for age, sex, race, prior cardiac surgery, smoking, diabetes, induction immunosuppression, recipient and donor cytomegalovirus and Ebstein-Bar virus status was used to estimate subhazard ratio (SHR).

Results:
Of the total of 29,717 patients with HT were included, 1,017 (3.4%) had CHD. Patients with CHD were younger, more likely to be female, and more likely to have had prior cardiac surgery. After multivariable competing-risk regression, CHD was associated with higher risk of PTM (aSHR 1.44, 95% CI 1.15 – 1.80) and hematologic malignancy (aSHR 2.09, 95% CI 1.28 – 3.42). Among patients < 45 years old, CHD had an unadjusted SHR of 1.55 (95% CI 1.11 – 2.16) of PTM, Figure.

Conclusions:
Among adult patients with HT, CHD was associated with increased risk of PTM and hematologic malignancy. Further investigation is warranted to identify risk factors and screening strategies for malignancy in this patient population.
Abstract 4118959: Pulmonary Artery-Targeted Metformin-Loaded Nanocapsules Enhance Treatment of Pulmonary Arterial Hypertension
Authors: Chida-Nagai Ayako , Masaki Naoki , Sato Hiroki , Kato Tatsuya , Takakuwa Emi , Matsuno Yoshihiro , Manabe Atsushi , Takeda Atsuhito
Published: November 2024

Background:
Pulmonary arterial hypertension (PAH) remains a therapeutic challenge despite the availability of various medications. Metformin can be able to treat PAH but is associated with significant side effects. This study aims to enhance the efficacy and safety of metformin through a novel drug delivery system using low-dose metformin encapsulated in pulmonary artery-targeted nanocapsules.

Methods:
Metformin-loaded lung-targeted nanocapsules (MET nanocapsules) were synthesized using a specific lipid composition, including cationic lipids. The uptake and effects on cell viability were assessed in human pulmonary arterial smooth muscle cells (hPASMCs) from both healthy individuals and PAH patients. The therapeutic efficacy of MET nanocapsules was evaluated in a rat model of PAH. Safety was confirmed via serum biochemical tests in rats.

Results:
MET nanocapsules were successfully synthesized and demonstrated significant inhibition of PASMC proliferation. In the PAH rat model, MET nanocapsule treatment led to improved hemodynamic parameters, reduced right ventricular hypertrophy, and decreased pulmonary arterial medial thickening. Importantly, MET nanocapsules showed effective accumulation in the lungs of PAH rats.

Conclusions:
Intravenous administration of MET nanocapsules represents a safe and innovative therapeutic approach for PAH. This targeted delivery system has the potential to improve treatment outcomes while minimizing side effects and may have broader applications for other forms of pulmonary hypertension.
Abstract 4119213: A Novel Animal Model for Pulmonary Hypertension: Lung Endothelial Specific Deletion of Egln1 in Mice
Authors: Liu Bin , Yi Dan , Ramirez Karina , Fallon Michael , Dai Zhiyu
Published: November 2024

Background:
Pulmonary arterial hypertension (PAH) is a disastrous disease that is characterized by high blood pressure in the pulmonary arteries which has the potential to lead to heart failure over time. Previously, our lab found that endothelial-specific knockout of
Egln1
, encoding prolyl 4-hydroxylase-2 (PHD2), induced spontaneous pulmonary hypertension (PH). Recently, we elucidated that
Tmem100
is a lung-specific endothelial gene using

Tmem100
CreERT2

mice. We reason that lung endothelial-specific deletion of
Egln1
could lead to the development of PH without affecting other organs’
Egln1
gene expression and defect.

Methods:
Tm
em100-CreERT2 mice were crossed with

Egln1
flox/flox

mice to generate

Egln1
f/f
; Tmem100 CreERT2

(LiCKO) mice. Western blot and immunofluorescent staining were performed to verify the knockout efficacy of
Egln1
in multiple organs of LiCKO mice. PH phenotypes including hemodynamics, right heart size and function, and pulmonary vascular remodeling were evaluated by right heart catheterization and echocardiography measurement.

Results:
Tamoxifen treatment induced
Egln1
deletion in the lung ECs but no other organs in adult LiCKO mice. LiCKO mice exhibited an increase in right ventricular systolic pressure (RVSP, ~35 mmHg) and right heart hypertrophy. Echocardiography measurement showed right heart hypertrophy and cardiac and pulmonary arterial dysfunction. Pulmonary vascular remodeling including pulmonary wall thickness and muscularization of distal pulmonary arterials was enhanced in LiCKO mice compared to wild-type mice.

Conclusions:
Tmem100
promoter-mediated lung endothelial knockout of
Egln1
in mice develops spontaneous PH. LiCKO mice could be a novel mouse model for PH to study lung and other organ crosstalk.
Abstract 4119280: The role of colony-stimulating factor 1 receptor and perivascular macrophages in pulmonary arterial hypertension
Authors: Nishiura Kazuto , Yokokawa Tetsuro , Miura Shunsuke , Sato Akihiko , Shimizu Takeshi , Misaka Tomofumi , Oikawa Masayoshi , Yoshihisa Akiomi , Sugimoto Koichi , Nakazato Kazuhiko , Ishida Takafumi , Takeishi Yasuchika
Published: November 2024

Background:
Pulmonary arterial hypertension (PAH) is a life-threatening disease caused by pulmonary artery remodeling, inflammation, and altered immune responses. The proliferation of pulmonary arterial smooth muscle cells and the accumulation of perivascular macrophages are crucial factors for the development of pulmonary artery remodeling. However, the mechanism for the progression of pulmonary artery remodeling through the perivascular macrophages has not been fully investigated. In this study, we examined the significance of colony-stimulating factor 1 receptor (CSF1R), which regulates the differentiation and proliferation of macrophages in PAH.

Methods and Results:
The numbers of pulmonary arterial perivascular CSF1R-positive cells significantly increased in lungs from PAH patients, compared to controls. The CSF1R phosphorylation on whole lungs was significantly increased in monocrotaline (MCT)-induced PAH rats and SU5416/Hypoxia (SuHx)-induced PAH mice. Next, we evaluated the therapeutic potential of a CSF1R inhibitor or anti-CSF1R antibody
in vivo
. Blocking CSF1R with a CSF1R inhibitor or anti-CSF1R antibody significantly decreased right ventricular systolic pressure, right ventricular fibrosis, perivascular CD68-positive macrophages and Arg1-positive M2 macrophages in PAH rats and mice. CSF1R knockdown using antisense oligonucleotide in the lung significantly decreased right ventricular systolic pressure in SuHx-induced PAH mice. Next, we focused on C-C motif chemokine ligand 2 (CCL2) whose gene expression is elevated in macrophages of PAH model. The culture with a conditioned medium from lung-derived M2 macrophages accelerated the proliferation of pulmonary arterial smooth muscle cells, while adding a CCL2 neutralizing antibody into the conditioned medium inhibited their proliferation.

Conclusion:
CSF1R has a critical role in the proliferation of pulmonary arterial perivascular macrophages and the progression of PAH, and M2-derived CCL2 contributed to the proliferation of pulmonary arterial smooth muscle cells. CSF1R is a novel therapeutic target in PAH.
Abstract 4119426: Enhancing early detection of ICI myocarditis cases during hospitalization: A role for large language models
Authors: Sun Virginia , Heemelaar Julius , Hadzic Ibrahim , Raghu Vineet , Wu Chia-Yun , Zubiri Leyre , Ghamari Azin , Suero-Abreu Giselle , Wu Jessica , Hathaway Nora , Gilman Hannah , Villani Alexandra-Chloe , Ho Jor Sam , Zlotoff Daniel , Blum Steven , Sullivan Ryan , Reynolds Kerry , Neilan Tomas
Published: November 2024

Background:
Immune-checkpoint inhibitor (ICI)-induced myocarditis is the most fatal immune-related adverse event (irAE). Early recognition and treatment of ICI myocarditis is associated with improved outcomes. However, current approaches to the diagnosis of ICI myocarditis have limitations. Open-source large language models (LLMs) are an accessible and scalable method of answering queries from human-generated text, and therefore may assist in the real-time early detection of ICI myocarditis among at-risk patients.

Research Question:
Can a free, open-source LLM detect cases of ICI myocarditis early in admission?

Aims:
We investigated the ability of a LLM pipeline to screen for ICI myocarditis within one day of admission using hospital medical records.

Methods:
Hospital admissions of patients on ICI therapy from November 4th, 2021, to September 5th, 2023 were retrospectively reviewed by a multidisciplinary immunotoxicity team using established, published definitions for the presence of ICI myocarditis. Progress notes written the day before, day of, and day after admission were fed into an open-source LLM pipeline built using Mistral 7B OpenOrca with retrieval augmentation generation (RAG). Performance of the LLM was measured via sensitivity and specificity in comparison to the gold standard of manual adjudication.

Results:
Of the 1874 hospital admissions of patients on ICI therapy, there were 22 (1.2%) cases of myocarditis. The average time to initiation of treatment was 2.45 days. Using notes written within one day after admission, the LLM detected ICI myocarditis with 95.5±8.7% sensitivity and 95.4±1.0% specificity, spending 2.13 seconds per chart.

Conclusion:
LLMs serve as a useful tool to screen for ICI myocarditis, detecting 95.5% of cases within one day of admission with 95.4% specificity. Future studies will investigate if integrating this tool into the real-time management of irAEs could lead to earlier diagnosis, faster initiation of treatment, and improved patient outcomes.
Abstract 4119913: Aging-Associate Peptide Medin Induces Proinflammatory Activation in Human Brain Vascular Smooth Muscle Cells
Authors: Karamanova Nina , Morrow Kaleb , Maerivoet Alana , Madine Jillian , Lozoya Maria , Weissig Volkmar , Li Ming , Migrino Raymond
Published: November 2024

Background:
Medin is one of the most common amyloidogenic proteins and accumulates in the vasculature with aging. Vascular medin accumulation is associated with Alzheimer's disease, vascular dementia and aortic aneurysms.
In vitro
, medin has been shown to induce endothelial proinflammatory activation and in
ex vivo
human cerebral arterial tissue, medin induces both endothelial and smooth muscle dysfunction. The role of medin in vascular smooth muscle (VSMC) activation remains unknown.

Aim:
The aim of the study is to determine using gene transcription assay whether medin induces VSMC activation and phenotypic transformation.

Methods:
Human brain vascular smooth muscle cells (HBVSMCs, passages 6-10) were exposed to medin at doses observed in human tissues (0, 0.5, 1 and 5 υM) for 20 hours and reverse transcription polymerase chain reaction (rtPCR) was used to quantify gene expression of proinflammatory factors (interleukin (IL)-6, IL-8, IL-1b) and structural and enzyme proteins associated with VSMC phenotypic transformation (ACTA2, MYH11 and NOX4). In separate experiments, HBVSMCs were exposed to vehicle, medin 5 υM without or with small molecule NFκB inhibitor RO106-9920 (10 υM) or NLGM1 nanoliposome (70% phosphatidylcholine, 25% cholesterol, 5% monosialoganglioside, 100 υg/mL, agent shown to reverse medin-induced endothelial dysfunction and proinflammatory activation).

Results:
Medin induced a dose-dependent increase in gene expression of IL-6, IL-8 and IL-1b but did not alter gene expression of ACTA2, MYH11 and NOX4 (Fig. 1). Co-treatment of medin with RO106-9920 and NLGM1 showed a trend (not statistically significant) of reduced IL-6 and IL-8 (Fig. 2).

Conclusions:
Physiologic doses of medin induced pro-inflammatory activation of HBVSMCs but did not affect gene expression of structural proteins (ACTA2 and MYH11) and enzyme (NOX4) involved in VSMC phenotypic transformation. Although the mechanisms behind this effect remains to be explored, results suggest that medin may be an important mediator of aging-associated vascular inflammation.
Abstract 4120274: Symptom cluster profiles predict all-cause mortality among U.S. community-dwelling older adults with heart failure
Authors: Wang Zequan , Walsh Stephen , Jeon Sangchoon , Conley Samantha , Chyun Deborah , Redeker Nancy
Published: November 2024

Background:
Individual symptoms are predictors of mortality in adults with heart failure (HF). However, symptom clusters may be more predictive of future risks than isolated symptoms, yet research on these symptom clusters in older adults with HF is limited.

Aims:
To explore the extent to which symptom cluster profiles predict all-cause mortality among community-dwelling older adults with HF, while adjusting for known risk factors.

Methods:
We conducted a secondary analysis of data of the 2008 to 2016 surveys of the U.S. Health and Retirement Study using latent class analysis to identify baseline cluster profiles, and survival analysis for time to death with Cox proportional hazard (Cox PH) models, and Kaplan Meier survival analyses.

Results:
We included 684 participants [mean age=74.9, (SD=10) years, 56.6% female, 16.2% Black/African American]. Three baseline symptom cluster profiles were identified: high-burden (pain, shortness of breath, fatigue, swelling, depressive symptoms, dizziness), low-burden, and cardiopulmonary-depressive (shortness of breath, pain, and dizziness). The estimated median time-to-death was 71 (95% CI=64, 79) months. Of the 364 participants in the cardiopulmonary-depressive profile, 240 (65.9%) died (median time= 65 months, 95% CI= 55, 73) compared to those in the low-burden profile, of which 49% died. Approximately 61% in the high burden profile died (median time=67 months, 95% CI= 51, 90). A significant difference in survival times between the 3 cluster profiles was found (Log-rank= 9.13,
p
= 0.01). In the adjusted Cox PH model, participants in the high symptom burden and respiratory-depressive distress profiles had adjusted HR of 1.48 (95% CI=1.15, 1.94) and 1.44 (95% CI=1.14, 1.80) compared to those in the low burden symptom cluster profile, after controlling for age, gender, smoking, and comorbidities.

Conclusions:
The identified symptom cluster profiles predict 8-year all-cause mortality in older adults with HF, after controlling for known risk factors. An evaluation of symptom clusters, rather than individual symptoms, may provide additive prognostic information.
Abstract 4120458: Predictors of School Non-Engagement in School Aged Children and Adolescents Born with Heart Disease
Authors: Hodgson Sarah , Peterson Jennifer
Published: November 2024

Introduction:
School engagement, or caring about doing well and doing required homework, is an important factor for academic success and may contribute to poorer academic outcomes in children born with heart disease (HD), compared to heart-healthy peers. Factors that influence lack of school engagement in children born with HD are not well known.

Research Question:
What factors predict school non-engagement in students with HD?

Aims:
To identify factors that predict school non-engagement in students with HD to assist in earlier detection and support for students at increased risk.

Methods:
We analyzed data from the 2022 National Survey of Children’s Health (NSCH), using procedures for complex weighted survey data. School-related outcomes in children ages 6 to 17 years born with and without HD were compared using Chi-square tests. Multivariate logistic regression was used to examine predictors of school non-engagement in students with HD.

Results/Data:
Of 54,065 NSCH responses, 34,284 were children ages 6 to 17 years, and 826 of these were born with HD. Children born with HD had lower school engagement (p<0.001) and missed more days of school (p<0.001) than peers not born with HD, but grades were not different between groups. Students born with HD were more likely than peers not born with HD to be bullied (p = 0.001), have a diagnosis of anxiety (3.71% vs 1.95%, p<0.001) or depression (3.56% vs 2.09%, p =0.012), require a Special Education Plan (34.9% vs 16.1%, p<0.001), or to receive mental health services (23% vs 14%, p <0.001). Multivariate logistic regression identified factors that significantly predicted school non-engagement in students born with HD, including diagnosis of attention deficit/hyperactivity disorder (ADHD) (aOR 1.94, 95% CI [1.20, 4.58], p=0.013), behavior/conduct problems (aOR 2.77, 95% CI [1.46, 5.23], p=0.002), or learning disability (aOR 3.44, 95% CI [1.79, 6.59], p<0.001). Sociodemographic variables, days of missed school, anxiety, depression, intellectual disability, autism spectrum disorder, and speech disorder were not significant predictors of school non-engagement. Special healthcare needs status neared significance in predicting lack of school engagement (p = 0.056)

Conclusions:
We identified ADHD, behavior/conduct problems, and learning disabilities as predictors of school non-engagement in students with HD. This information can be used to identify at-risk students born with HD who may benefit from proactive screening and support.
Abstract 4120496: Cannabis Use Among Heart Failure Hospitalizations and Cardiovascular Outcomes. A Five-Year Retrospective Study
Authors: Evbayekha Endurance , Mikhalkova Deana , Enyi Chioma , Oladunjoye Adeolu , Ilonze Onyedika
Published: November 2024

Introduction:
The use of cannabis is on the rise. A few retrospective studies have demonstrated an association between cannabis use and ischemic heart disease and stroke. However, its implications in the already established heart failure (HF) population has not been well studied. We aimed to address this gap.

Methods:
We employed the National Inpatient Sample database (2016-2020) and used ICD-10 codes to identify all patients ≥18 years old with a history of HF. Then, we divided them into two groups: those with and without a history of cannabis use. A greedy nearest-neighbor 1:1 propensity score matching (PSM) followed by multivariable logistic regression analysis was used to account for baseline differences (including cigarette smoking) and to predict the outcomes. The outcomes were ST-segment elevation myocardial infarction (STEMI), non-STEMI (NSTEMI), uncontrolled hypertension (HTN), arrhythmias, acute kidney injury (AKI), and stroke.

Results:
Of the 4,283,620 HF hospitalizations, 1.6% (67,795) used cannabis, and 72% (48,825) were male. Compared to the non-cannabis group, the group with cannabis use was younger, with a mean age of 53 vs 68 years, p<0.0001.

After PSM, 56,233 with a history of cannabis use were matched to 56,233 hospitalizations without cannabis use history. The population with cannabis use had a higher association with uncontrolled HTN 1.5 (1.4-1.6), NSTEMI 1.3 (1.23-1.36), STEMI 1.15 (1.05-1.25), stroke 1.14 (1.05-1.23), and AKI 1.05 (1.02-1.1), (p<0.0001, for each). Arrhythmias 0.96 (0.94-1.01, p=0.1) did not differ between both groups.

Conclusion:
Among the hospitalized HF population, those with a history of cannabis use had a higher association with uncontrolled HTN, STEMI, NSTEMI, AKI, and stroke. They were also younger than their non-cannabis use counterparts. More research is needed to determine the significance of these findings.
Abstract 4120716: Aspirin plus clopidogrel versus aspirin alone in patients with mild-to-moderate stroke: A systematic review and meta-analysis
Authors: Ahmed Mushood , Nadeem Zain , Ahsan Areeba , Fatima Eeshal , Fatima Laveeza , Zahra Rubab , Jain Hritvik , Ahmed Raheel , Gole Shrey , Ahmad Adeel , Ramphul Kamleshun , Shahid Farhan
Published: November 2024

Background:
Studies have shown that dual antiplatelet therapy (DAPT) is superior to aspirin monotherapy in patients with minor stroke or transient ischemic attacks. However, there is limited evidence regarding the efficacy and safety of DAPT in mild-to-moderate stroke.

Aims:
We conducted a systematic review and meta-analysis to evaluate whether DAPT is superior to single antiplatelet among patients with mild to moderate ischemic stroke.

Methods:
PubMed/MEDLINE, Embase, the Cochrane Library, and ClinicalTrials.gov were searched from inception till March 2024 for published randomized controlled trials (RCTs) and observational studies that compared aspirin plus clopidogrel versus aspirin monotherapy in patients with mild-to-moderate stroke. R version 4.3.2 was used to calculate risk ratios (RRs) with 95% confidence intervals (95% CIs).

Results:
A total of 4 studies reporting data for 15,173 patients were included. DAPT was associated with a reduced risk of early neurological deterioration (END) (RR: 0.55, 95% CI: 0.28 to 1.05, p = 0.07 Figure 1A) and recurrent ischemic stroke (RR: 0.65, 95% CI: 0.41 to 1.04, p = 0.07 Figure 1B) without reaching statistical significance. The risk of recurrent hemorrhagic stroke (RR: 0.94, 95% CI: 0.47 to 1.86, p = 0.86 Figure 2A), all-cause death (RR: 0.75, 95% CI: 0.52 to 1.08 Figure 2B), or myocardial infarction (RR: 0.83, 95% CI: 0.45 to 1.54 Figure 2C) was comparable across the two groups. DAPT was not associated with an increased risk of any bleeding event (RR: 0.70, 95% CI: 0.36 to 1.36 Figure 2D).

Conclusion:
DAPT possibly reduces the risk of END and recurrent ischemic stroke as compared to aspirin monotherapy in mild or moderate stroke without increasing the risk of bleeding events.