bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 4142969: Temporary Mechanical Circulatory Support Modulates Inflammation And Fibrosis In Cardiogenic Shock Patients Bridged To Cardiac Replacement.
Authors: Krishnamoorthi Muthu Kumar , Patel Khush , Bhimaraj Arvind
Published: November 2024

Background:
Temporary mechanical circulatory support devices (t-MCS) facilitate recovery of the patients, to then bridge them to cardiac replacement. A new paradigm of resting and recovering the heart with a t-MCS device is being explored. The understanding of mechanisms of recovery with t-MCS’s could facilitate the modulation of specific pathways to promote recovery. We compare the impact of two widely used t-MCS strategies in heart failure (HF): percutaneous left ventricular assist device (HFpVAD) vs Intra-aortic balloon pump (HFIABP) on the genetic landscape of the heart tissue in patients being bridged to cardiac replacement.

Hypothesis
Cardiac tissue of patients treated with pVAD will have distinct changes when compared to IABP supported hearts in relation to unsupported heart failure tissue.

Methods:
Myocardial tissue was collected at the time of surgery from 4 patients bridged with a pVAD (Impella 5.5) and 4 bridged with IABP. Tissues from patients who were bridged without MCS were used as HF tissues. Bulk RNA paired-end sequencing of cardiac tissues was performed on an Illumina Hiseq 4000 was performed. StringTie was used to perform expression levels for mRNAs.

Results:
Gene ontology (GO) analysis of the differentially expressed genes (DEG) resulted in GO terms such as extracellular matrix, cytokine activity, and adaptive immune response indicated that most of the DEG were contributing to the regulation of fibrosis and inflammation related functions. KEGG analysis of the DEG resulted in pathway terms such as malaria, complement and coagulation cascades, ECM receptor interaction, and cell adhesion molecules. Interestingly, the predominance of ECM/fibrosis-related pathways and infection/immune system pathways in both GO and KEGG analysis signals the involvement of these pathways in the t-MCS assisted resting of the cardiac tissue in patients with cardiogenic shock.

Conclusion:
Our results illustrate that t-MCS in general modulates fibrosis and inflammation related genes with unloading with p-VAD having distinct changes with more genes when compared to IABP support. Further studies exploring these mechanisms could discover a therapeutic focus for promoting t-MCS assisted myocardial recovery.
Abstract 4142981: Incidence and Predictors of Symptom-Arrhythmia Association During Holter Monitoring
Authors: Saraiya Avinash , Corsi Douglas , Farhan Saaniya , Hazlewood Cameo , Qiu Grace , Pavri Behzad
Published: November 2024

Introduction:
Reported symptomatic activations by patients who are prescribed Holter monitors often do not correlate with true arrhythmia, and recorded ectopy is often asymptomatic. The prevalence of symptom-arrhythmia association (SAA) and relation with age, sex, and underlying co-morbidities are not well described.

Goals:
Identify the overall likelihood of symptoms being associated with true arrhythmia. Identify patient characteristics associated with SAA.

Methods:
In this retrospective chart review, extended Holter recordings (analyzable data >72 hrs) from 100 consecutive patients (Apr-Jul 2023) were selected. Patients activated the monitor when they experienced an arrhythmia-related symptom. Holters with excessive artifact and <2 symptomatic activations were excluded. Accuracy was defined as the percent of activations associated with arrhythmia (APB, VPB, SVT, VT, 2nd/3rd degree AV block, or sinus exit block). We defined “SAA” as accuracy greater than zero.

Patient characteristics were characterized as mean or percent (Table I). The relationship between important predictor variables and the presence of SAA was further explored using logistic regression (adjusting for sex, race, analysis duration, comorbidities and ectopy percent, Table II). Analyses were run in RStudio R 4.2.1.

Results:
For 100 patients (mean age: 55±18, 27% male, 66% Caucasian), the average accuracy was 22%. Of the 100 patients, 42 had SAA. On univariate analyses, patients with SAA were more likely to be older, have a lower LVEF, and be on cardioactive medications. None of these associations were significant after multivariable adjustment for variables shown in Table II. There was no difference in the percentage of females, percent Caucasians, presence of MVP, or the number of symptomatic activations in those with SAA versus without.

Conclusion:
The average probability of a symptomatic event during Holter recording being associated with a true rhythm disturbance was 22% and only 42% of patients demonstrated any SAA. There was no association between SAA and sex, number of symptomatic activations, or the presence of MVP.
Abstract 4142982: Long-Term Myocardial Tissue Characterization in Women with Preeclampsia
Authors: Roy Rukmini , Wang Haonan , Huang Sherry , Minga Iva , O'Hara Meaghan , Tang Maxine , Wang Shuo , Slivnick Jeremy , Polonsky Tamar , Rana Sarosh , Lang Roberto , Shahul Sajid , Patel Hena
Published: November 2024

Introduction:
Preeclampsia, a pregnancy-specific complication, is an established risk factor for long-term cardiovascular complications, including heart failure with preserved ejection fraction (HFpEF), however, the exact mechanism of this cardiovascular dysfunction remains unclear. This study aimed to characterize the cardiac structure and myocardial tissue using cardiac magnetic resonance imaging (CMR) in women with a long-term history of preeclampsia. We hypothesized that prior preeclampsia is associated with myocardial fibrosis or scarring.

Methods:
Women with singleton pregnancies delivered between 2004 and 2019 were identified and prospectively enrolled to undergo CMR (1.5T Signa Artist GE HealthCare) with cine imaging, tissue multiparametric quantitative mapping and late gadolinium enhancement (LGE) imaging.

Results:
Twenty-three subjects (41.0±6 years, 12.7±5 years post-partum) were included. Women with a history of preeclampsia (n=11) were compared to a healthy control group of women with prior normotensive, uncomplicated pregnancy (n=12). There was no significant difference in LV systolic function, LV mass, T1 and T2 mapping, or LGE between the preeclamptic group versus controls, although right ventricular (RV) systolic function was significantly higher (65±7.5% vs 58±7.7%; p=0.04) in individuals with preeclampsia (
Panel A
). Notably, global extracellular volume fraction (ECV) was significantly higher in women with preeclampsia versus normotensive pregnancies (47.2±21.2% vs 31.0±4.8% respectively; p=0.02) (
Panel B
).

Conclusions:
Global myocardial ECV appears to be increased with preeclampsia, many years after the index pregnancy, potentially reflecting diffuse interstitial fibrosis. Diffuse fibrosis may stiffen the myocardium and reduce myocardial compliance, resulting in loss of diastolic function. Further research is needed to determine whether these alterations in cardiac structure and increased myocardial fibrosis contribute to preeclampsia-associated HFpEF and cardiovascular outcomes.
Abstract 4142987: Cardiac TRPM7 kinase plays a key role on diabetic heart failure with preserved ejection fraction
Authors: Liu Man , Liu Hong , Kang Gyeoung-Jin , Hartweck Lynn , Feng Feng , Prins Kurt , Dudley Samuel
Published: November 2024

Introduction:
Hypomagnesemia (HypoMg) and subsequent oxidative stress cause diabetic cardiac diastolic dysfunction (DD) and heart failure with preserved ejection fraction (HFpEF). A Mg
2+
transporter with both channel and kinase function, the transient receptor potential cation channel subfamily M 7 (TRPM7), is upregulated in HypoMg. Inhibition of TRPM7 kinase prevents HypoMg-mediated oxidative stress in the brain.

Aims:
We investigated the role of TRPM7 kinase in cardiomyocyte mitochondrial regulation and DD.

Methods:
Wild type (WT) C57BL/6J mice and transgenic mice with a global K1646R mutation in the TRPM7 kinase domain, TRPM7
K1646R
(without kinase function) were fed with either a normal diet (control, 2000 mg/kg Mg
2+
), high fat diet (HFD, 60% kcal from fat), or a low Mg
2+
diet (HypoMg, 15-30 mg/kg Mg
2+
) starting from 10 weeks old. HFD lasted for 23-25 weeks. HypoMg diet lasted for 6 weeks. Mouse ventricles, cardiomyocytes, and mitochondria and human cardiac cell line, RL-14, were used for analysis.

Results:
Diabetic mice on HFD had HypoMg and elevated TRPM7 protein levels in heart. DM-associated DD was prevented by TRPM7
K1646R
. In HypoMg mouse ventricles, TRPM7 mRNA and protein levels were also increased. HypoMg-induced DD (increased E/e’, decreased resting sarcomere length, and increased S-glutathionylated cardiac myosin binding protein C) and mitochondrial dysfunction (increased mitoROS, depolarized mitochondrial membrane potential, and decreased ATP, mitochondrial Mg
2+
and complex I/II activities) were prevented by TRPM7
K1646R
. TRPM7 kinase regulated the overexpression of a Src kinase family member Fgr in mitochondria of HypoMg mouse ventricles, which co-localized with complex II, regulated complex II activity, and led to increased mitoROS.

Conclusion:
TRPM7 mediated mitochondrial dysfunction and cardiac DD in HypoMg. TRPM7 kinase enhanced Fgr expression in mitochondria, with subsequent complex II dysfunction and mitoROS overproduction. Inhibition of TRPM7 kinase function represents a potential novel therapeutic strategy to treat diabetic HFpEF.
Abstract 4143039: Circulating Follistatin-like 3 and Risk Prediction of Hypertensive Emergency in Patients with Suspected Preeclampsia
Authors: Azzi Marly , Potchileev Sanela , Dreixler John , Mueller Ariel , Rana Sarosh , Shahul Sajid
Published: November 2024

Background:
Hypertensive emergency in pregnancy, defined as systolic BP ≥160 and/or diastolic BP ≥110, is a serious complication of hypertensive disorders of pregnancy (HDP). Rapid, aggressive treatment of severe HTN decreases severe Maternal morbidity by 50%. However, few clinical indicators or biomarkers predict the development of severe HTN in pregnancy. Follistatin-like 3 (FSTL3), has been implicated in the development of preeclampsia. We hypothesized that elevated levels of FSTL3 in women for suspected preeclampsia evaluation would predict the development of a hypertensive emergency in pregnancy within two weeks.

Methods:
This cohort study included patients with singleton pregnancies who presented in obstetric triage at the University of Chicago between July 2021 and July 2023 for suspected preeclampsia evaluation. We measured plasma levels of FSTL3 at presentation and examined for an association between FSTL3 and subsequent development of a hypertensive emergency within 2 weeks. We excluded women who presented with severe preeclampsia or HTN emergencies on presentation to triage. Logistic regression models with receiver-operating characteristic (ROC) analysis were used to determine the clinical utility of FSTL3 in predicting HTN emergencies.

Results:
Our study included 208 patients, of which 79 (37.98%) developed severe preeclampsia. The median age was 30 years old (IQR 25.5, 34.5); the median BMI was 36.47 (IQR 30.79, 42.40), and the majority were African American (72.60%). The median FSTL3 at presentation was significantly elevated in participants who experienced HTN emergency compared with those who did not, respectively (Median, IQR) (46.47ng/ml, IQR (33.51–66.10)] versus 31.59ng/ml IQR, 27.35, 43.35], P<0.0001). This association was significant after adjustment for maternal age, race, smoking, HDP, and BMI (P=0.03). Figure 1 outlines ROC analysis for specificity and sensitivity of FSTL3 in predicting HTN emergency within 2 weeks with the area under the curve =0.83.

Conclusion:
In women with suspected preeclampsia, circulating FSTL3 predicts a hypertensive emergency occurring within two weeks of triage presentation. This test may be helpful in risk stratification and management in women with HDP.
Abstract 4143066: C-C Chemokine Receptor Type 2 and Matrix Metalloproteinases Molecular Interaction in Rat Abdominal Aortic Aneurysm
Authors: Zaghloul Mohamed , Elizondo Benedetto Santiago , Arif Batool , Heo Gyu Seong , Luehmann Hannah , Liu Yongjian , Gropler Robert , Sadeghi Mehran , Zayed Mohamed
Published: November 2024

Background:
Abdominal aortic aneurysm (AAA) in part results from complex molecular interactions between inflammatory cytokines. C-C chemokine Receptor Type 2 (CCR2) and Matrix Metalloproteinases (MMPs) have fundamental roles in the initiation, progression, and rupture of AAAs. We hypothesized that in a preclinical rodent AAA model CCR2 and MMP molecular interactions are essential for AAA progression and rupture.

Aim:
Our study aimed to assess the correlation and molecular interaction between CCR2 and MMP in AAAs following pharmacological targeting of each.

Methods:
Male Sprague-Dawley rats underwent intraluminal infrarenal perfusion of the aorta using porcine pancreatic elastase (PPE), daily β-aminopropionitrile (BAPN) to promote AAA rupture. Starting on postoperative day 3 (POD3), rats were treated with either a MMP inhibitor (MMPi; GM6001) via daily intraperitoneal injection or a CCR2 inhibitor (CCR2i; RS504393) via daily oral gavage. On POD6, the treated and control groups underwent
in vivo
aortic diameter measurement using ultrasound then their AAA tissues were harvested. The rate of rupture of AAA was observed until POD14 (Fig 1A).

Results:
CCR2 was directly correlated with total, pro and active MMP9 (r=094, r=0.88, r=0.88, P<0.05 respectively; Fig 1B-D). CCR2i significantly decreased total, pro, and active MMP9; while MMPi significantly reduced CCR2 (Fig 1G-J). Both CCR2i and MMPi significantly decreased AAA diameter and rupture rate (Fig 1E-F). The CCR2i group had significantly lower IL-1β, IL-10, IL-18, and MCP-1 levels compared to the control group (Fig 1K-O). However, MMPi group had significantly lower IFN-γ and higher preserved elastin content compared to the control group (Fig 1Q-S). Both treatment groups had significantly lower IL-17A and higher TNF-α levels (Fig 1M-R).

Conclusion:
Our study demonstrates a positive correlation between CCR2 and MMP9, suggesting their interdependence in AAA pathogenesis. Furthermore, inhibition of either CCR2 or MMP9 reduced AAA development, highlighting their potential as therapeutic targets. Future studies using CCR2 and MMP9 knockout mice are needed to further elucidate the mechanistic interaction between these molecules in AAA pathogenesis.
Abstract 4143071: Comparative outcomes of cardiac arrest survivors with and without the use of neuromuscular blockers.
Authors: Dutta Abhishek , Patel Krunalkumar , Mondal Avilash , Bhatia Smriti , Doss Ramy , Majeed Chaudry , Qureshi Waqas , Dhar Sunil
Published: November 2024

Introduction:
Cardiac arrests result in significant mortality and morbidity, with therapeutic hypothermia (TH) being a mainstay in post-cardiac arrest care to enhance neurological outcomes. The use of neuromuscular blockade (NMB) agents with TH aims to manage shivering, ventilator asynchrony, and reduce cerebral oxygen demand. However with recent studies showing normothermia to be effective in achieving good neurological outcomes, the use of these agents remains debatable.This study investigates the comparative outcomes of cardiac arrest survivors with and without the use of NMB agents.

Methods:
A retrospective cohort study was conducted at a tertiary care hospital in North Carolina involving 4047 patients with cardiac arrest from 01/01/2012, to 12/12/2017. Adults surviving beyond 24 hours post-cardiac arrest were included, while those with a Glasgow Coma Scale ≥8, actively bleeding or pregnant patients were excluded. Demographic, comorbid variables and clinical outcomes were collected and analyzed to compare the efficacy of NMB use. We examined the 30 day mortality and neurological outcomes of both groups

Results:
Of total 976 patients, 364 (37.3%) received NMB agents.58.5% of patients received NMB as part of hypothermia protocol .Vasopressor use was also more in paralytic group (81.9% vs. 73.5%) p.004. There was no significant difference in 30-day (54.1% vs. 51.7%, p=0.45), 60-day (56.6% vs. 52.5%, p=0.2) mortality among two groups. The use of NMB agents was not associated with better neurological outcomes (66.2% vs 65.7%)

Conclusion:
The use of NMB agents in cardiac arrest survivors did not improve survival or neurological outcomes regardless of their use with or without therapeutic hypothermia. Compared to previous studies, our study did not find NMB agents to be superior. Further studies are needed to delienate the specific contexts when the use of NMB agents may be beneficial.
Abstract 4143127: Association of Serial Seattle Angina Questionnaire Assessments with Clinical Events in Chronic Coronary Disease: Insights from the ISCHEMIA Trial
Authors: O'Keefe Evan , Jones Philip , Cho Yoon Joo , Saxon John , Boden William , Stone Gregg , Bangalore Sripal , Reynolds Harmony , Maron David , Hochman Judith , Spertus John
Published: November 2024

Background:
Cross-sectional Seattle Angina Questionnaire (SAQ) scores not only measure patients’ symptoms, function and quality of life, but are also associated with prognosis in chronic coronary disease (CCD). Yet, the prognostic significance of serial SAQ scores in the modern era is unknown, particularly after revascularization.

Hypothesis:
Serial collection of SAQ scores can provide updatable estimates of clinical risk in patients with CCD.

Aims:
To describe the association of serial SAQ Summary Scores (SAQ-SS) with the primary endpoint of the ISCHEMIA trial (CV death, MI, or hospitalization for heart failure, unstable angina, or resuscitated cardiac arrest), stratified by medical management and recent revascularization.

Methods:
Analyses were framed from the perspective of a clinician reviewing the SAQ-SS in clinic and seeking to understand whether the prior score, the current score, or the change was most prognostic of subsequent clinical events. Cox models were created using the 3-month, 6-month, and change between the 3- and 6-month SAQ-SS scores, individually, as well as those scores in combination to find the most prognostic permutation. Each model was adjusted for 17 potentially confounding covariates. We performed separate analyses for the conservative and invasive management cohorts. In the conservative group, we excluded those who underwent revascularization prior to their 6-month assessment. In the invasive group, we included only patients who were revascularized within the first three months. In both groups, we excluded patients with events prior to 6 months.

Results:
In both the conservatively managed (n=1965) and recent revascularization (n=1447) cohorts, unadjusted analyses estimated a 6-9% lower risk of clinical events over a median of 3.2 years for each 5-point increase in SAQ-SS score. The current SAQ-SS score was most strongly associated with clinical events, even after including the prior SAQ-SS score and all other covariates (Table).

Conclusions:
Routine clinical use of the SAQ provides an updatable measure of risk in patients with CCD—managed either medically or with revascularization—with the current SAQ-SS score demonstrating the strongest association with clinical events.
Abstract 4143153: Correlation Between CRT Response and Patient-Reported Outcomes in Heart Failure with Reduced Ejection Fraction Patients
Authors: Paul Aritra , Demian Joe , Varma Niraj , Finet J. Emanuel , Kochar Arshneel , Bader Feras , Wazni Oussama , Tang Wilson , Rickard John
Published: November 2024

Background:
The correlation between CRT response and patient-reported outcomes is uncertain.

Objective:
To identify whether patient reported outcomes correlate with CRT response through a decision regret scale (DRS) in patients with heart failure with reduced ejection fraction (HFrEF).

Hypothesis:
CRT non-responders have more regret over having undergone device implant compared with responders.

Methods:
We included a total of 150 patients with HFrEF who underwent CRT implantation at the Cleveland Clinic from 2020-2022. Each patient was given a DRS questionnaire at 6 months post-CRT implant, and their CRT response status was assessed echocardiographically. Response was defined as an improvement in LVEF >5% with reduction in LVESV>10%. Patients were unaware of their response status at the time of filling out the questionnaire. The DRS Questionnaire asks patients whether they regret their decision to undergo a procedure. Patients rated, on a scale of 1 (strongly agree) to 5 (strongly disagree)- their agreement with five statements: It was the right decision; I regret the choice that I made; I would go for the same choice again; The choice did me a lot of harm; and The decision was a wise one. We grouped questions 1,3, and 5 from the DRS together for positive score (higher is more regret), and questions 2 and 4 were grouped together for negative score (lower is more regret). This data was compared between 2 groups based on responder (107; 71.33%) and non-responder status (43; 28.67%).

Results:
The median IQR positive score and negative score among all patients was 3 (3-5), and 10 (8-10) respectively. There were no patients who voiced significant regret for having undergone device implant. In comparing the scores between responders and non-responders, the Mann-Whitney U test revealed no difference in scores. [Median IQR positive score 3 (3-6) in non-responders, 3 (3-4.5) in responders; p=0.19; negative score 10 (8-10) non-responders,10 (9-10) in responders; p=0.44] (Figure 1).

Conclusion:
Patients with HFrEF undergoing CRT overwhelmingly do not regret their decision to undergo device implantation. The presence or absence of significant remodeling had no impact on patient satisfaction feelings towards the decision to undergo device implantation.
Abstract 4143160: Serotonin Norepinephrine Reuptake Inhibitor is Associated with Lower Mortality Among Patients Presenting with Takotsubo Cardiomyopathy
Authors: Shamaki Garba Rimamskep , Anuforo Anderson , SAFIRIYU ISRAEL , Corteville David , Sanghavi Monika , Clark Katherine
Published: November 2024

Background:
Serotonin-norepinephrine reuptake inhibitors (SNRIs) inhibit the presynaptic reuptake of serotonin and norepinephrine and are widely used in the treatment of depression and neuropathic pain. Some studies suggest that the use of SNRIs may play a role in the etiology of takotsubo cardiomyopathy.

Objectives:
We aim to evaluate the impact of serotonin-norepinephrine reuptake inhibitors on the clinical outcomes of patients with takotsubo cardiomyopathy.

Method:
The authors retrospectively analyzed the deidentified patient data from TriNetX research network. Patients aged ≥18 years with a principal diagnosis of takotsubo cardiomyopathy were identified from January 1, 2003, to December 31, 2023. Patients with a history of myocarditis, pheochromocytoma, acute myocardial infarction, cocaine-related disorders, opioid-related disorders, and patients on with an active prescription for 5-fluorouracil, capecitabine, gemcitabine, and trastuzumab were excluded. Additionally, patients on selective serotonin reuptake inhibitors, tricyclic antidepressants, modafinil, armodafinil, methylphenidate, bupropion and atomoxetine were excluded. We used propensity score matching to adjust for potential confounders. The final study population was divided into two cohorts: Patients on SNRIs (duloxetine, venlafaxine, and desvenlafaxine) and patients not on SNRIs. The primary outcome was all-cause mortality, and the secondary outcome was takotsubo cardiomyopathy-related complications.

Results:
A total of 16,853 patients with a diagnosis of takotsubo cardiomyopathy were identified, of which 2,482 (14.7%) were on SNRIs at the time of diagnosis. The SNRIs cohort was slightly older (mean age 64.1 vs. 63.4 years). Patients on SNRI had a higher proportion of Whites (76.2% vs. 66.5%). After propensity score matching, patients on SNRI had lower 7-day mortality (OR, 0.59; 95% CI, 0.41 – 0.84, p<0.01), cardiac arrest (OR, 0.58; 95% CI, 0.40 – 0.84, p<0.01), ventricular fibrillation (OR, 0.496; 95% CI, 0.248 – 0.995, p=0.04), and atrial fibrillation and flutter (OR, 0.74; 95% CI, 0.57 – 0.97, p=0.03). At 1 year, patients on SNRI had lower mortality (OR, 0.80; 95% CI, 0.67 – 0.96, p=0.02). On subgroup analysis, the use of duloxetine or venlafaxine alone was independently associated with lower 7-day mortality.

Conclusion:
The use of SNRIs among patients presenting with takotsubo cardiomyopathy is associated with lower mortality and lower takotsubo cardiomyopathy-related complications.
Abstract 4143186: Prior Statin Therapy Reduces Inflammation and Improves Outcomes in Patients Hospitalized for Covid-19: A Prospective Multicenter Cohort Study
Authors: Ismail Anis , Shadid Husam , Huang Yiyuan , Hutten Christina , Vasbinder Alexi , Pizzo Ian , Catalan Tonimarie , Machado Kristen , Blakely Pennelope , Banerjee Mousumi , Rubenfire Melvyn , Williams Geoffrey , Busui Rodica , Hayek Salim
Published: November 2024

Introduction:
Statins are lipid-lowering agents with anti-inflammatory effects. Data surrounding the benefits of statins in patients with coronavirus disease 2019 (Covid-19) are conflicting. We sought to better understand the impact of statins in the context of Covid-19-related inflammation.

Methods:
We leveraged the International Study of Inflammation in Covid-19, a prospective multicenter cohort study of patients hospitalized specifically for Covid-19 between February 1, 2020 and October 30, 2022. Participants underwent systematic assessment of biomarkers of inflammation. We used logistic regression modeling and inverse probability-of-treatment weighting (IPTW) to examine the association between prior statin use and the composite outcome of in-hospital death, need for mechanical ventilation, and need for renal replacement therapy.

Results:
A total of 4,464 patients were included in the study, of whom 1,364 (27.5%) were taking a statin prior to admission. There were 1,061 primary outcome events, including 540 deaths, 854 mechanical ventilation and 313 renal replacement therapy. Amongst biomarkers of inflammation, statin use was associated solely with lower levels of soluble urokinase plasminogen activator receptor (suPAR) after adjusting for known confounders. In multivariable logistic regression analysis, statin use was associated with lower odds of the composite outcome (adjusted odds ratio (aOR) 0.63, 95%CI[0.53-0.76]) compared to patients not on statins. Findings were consistent with IPTW (aOR 0.92, 95%CI [0.89- 0.95]). The proportion of the effect of statin on the primary outcome mediated by suPAR was estimated at 31.5%.

Conclusion:
Prior statin use is associated with improved outcomes and lower inflammation as measured by suPAR levels in patients hospitalized for Covid-19.
Abstract 4143204: Participation in a Resilience Intervention for Caregivers of Recently Hospitalized Patients with Heart Failure and Stroke
Authors: Abshire Saylor Martha , Clair Catherine , Curriero Samantha , Wang Natalie , Tenberg Amelia , Bahouth Mona
Published: November 2024

Introduction
Family caregivers of persons with advanced heart failure (HF) and stroke bear increased responsibilities as care recipients recover from acute hospitalization. Few formalized supports are available. We conducted a feasibility pilot of a caregiver-targeted support program: Heart Failure and Stroke Resilience Intervention for Caregivers (HEROIC) using a randomized waitlist-control design. Here we sought to understand similarities and differences in participation between HF and stroke enrolled caregiver participants.

Methods
We recruited caregivers of HF and stroke patients via review of the electronic health record and/or provider referral after the first follow-up visit. Baseline surveys were collected electronically. Enrolled participants were randomized to the intervention or waitlist group. HEROIC consists of 5 nurse-led, remote sessions over a 10-week period. Components incorporate resilience resources including emphasis on caregiver life purpose and values, goal-setting for self-care, social support, community and palliative care resources. Characteristics of participants were analyzed using descriptive statistics and t-test or chi-square as appropriate.

Results
We identified 158 potential caregivers through electronic health records and provider referral. 65% (n=103) were reached by phone and 57/103 (55%) were eligible for participation. Fifty caregivers consented but only 31 completed baseline data collection and were randomized. Reasons for drop out included loss to follow-up, patient death and too many competing demands. Caregivers were on average 58.4 years old (SD: 11.4), 84% female and 45% Black. They supported patients with moderate to severe functional impairment and 5.5 ± 2.3 instrumental activities of daily living (IADL) on average. Over half of caregivers reported financial strain. Caregivers reported moderate caregiver strain using the Modified Caregiver Strain Index (Mean: 11.9, SD: 6.0). Most caregivers supported persons with HF (n=19). The only statistically significant difference noted between HF and stroke caregivers was gender; more caregivers of stroke patients were male.

Conclusions
Similarities in baseline characteristics of HF and stroke caregivers suggest similar caregiving experiences. HEROIC or other early post-hospital caregiver support interventions may appeal to caregivers to increase resilience to the stresses of transitions of care but recruitment strategies require additional consideration.
Abstract 4143297: A Risk Prediction Score for Shockable Sudden Cardiac Arrest: Validation in the Framingham Heart Study
Authors: Truyen Thien Tan Tri Tai , Lin Honghuang , Mathias Marco , Chugh Harpriya , Reinier Kyndaron , Benjamin Emelia , Chugh Sumeet
Published: November 2024

Introduction
Individuals with shockable sudden cardiac arrest (SCA) have higher survival if treated with an implantable cardioverter defibrillator or automated external defibrillator. We previously developed VFRisk Score from an ongoing US West Coast study, which performs significantly better than left ventricular ejection fraction<35% (C-statistic 0.81 vs 0.64).

Hypothesis
The VFRisk score predicts sudden cardiac death (SCD) in a US East Coast community-based cohort, the Framingham Heart Study (FHS).

Methods:
We performed a nested case-control study in the FHS to test VFRisk. Cases were subjects who suffered SCD among the Original and Offspring cohorts. Controls were randomly selected at a ratio of 1:3, matched on age, sex, cohort, and exam. Demographic features and comorbidities were assessed from the FHS exam closest to the SCD event. VFRisk was the sum of 13 risk factors, each multiplied by its respective coefficient including diabetes (1.4), myocardial infarction (MI, 1.4), atrial fibrillation (AF, 1.8), stroke (1.7), heart failure (HF, 2.1), chronic pulmonary disease (1.5), seizure disorder (3.5), syncope (2.8), heart rate ≥75 (1.5), prolonged QTc (1.7), Tpeak-end ≥90ms (1.7), delayed intrinsicoid deflection ≥50ms (2.1), and echocardiogram left ventricular hypertrophy (2.4). Intrinsicoid deflection was excluded due to data unavailability.

Results:
Among 312 cases and 935, mean ages were 69.5 and 69.7 years, respectively, with 70.8% male in both groups. SCD cases had a significantly higher prevalence of diabetes, HF, stroke, AF, and MI compared to the control group. The VFRisk score was replicated with good discrimination (C-statistic 0.71, 95% CI 0.66-0.77) for SCD. SCD cases had higher VFRisk scores than controls (3.8±2.8 vs. 1.8±1.7, p<0.001). A 1-unit increase in VFRisk score was associated with a 48% increase of SCD (odds ratio 1.48; 95% CI 1.34-1.64). The highest risk score quartile was associated with 6-fold higher odds of SCD than the lowest quartile.

Conclusion:
The VFRisk score to predict shockable SCA was successfully replicated in the FHS. The differences in discrimination between the two studies could be explained by the inability to distinguish shockable versus non-shockable SCA in the FHS.
Abstract 4143312: Impact of Angiotensin Receptor Neprilysin Inhibitor on Chronic Heart Failure with Reduced Ejection Fraction in Adult Congenital Heart Disease Patients: A Systematic Review and Meta-analysis
Authors: Das Bibhuti , Deshpande Shriprasad , Nikolaidis Lazaros , Hernandez-Montfort Jaime , Niu Jianli
Published: November 2024

Background:
Heart failure (HF) in adults have benefitted significantly from addition of angiotensin receptor-neprilysin inhibitor (ARNI). However, limited data exist on the efficacy and safety of ARNI in adults with congenital heart disease (ACHD) related HF.

Methods:
We conducted a comprehensive search of 3 major databases- PubMed, Scopus, and Embase, and collected articles published the use of ARNI for HF in ACHD patients who were already receiving angiotensin-converting enzyme inhibitors (ACEi)/angiotensin receptor blockers (ARB), beta-blockers, and mineralocorticoid antagonists. We excluded articles on acute decompensated HF and HF with preserved ejection fraction. The primary outcome was the change in NYHA functional class (FC). Additionally, we evaluated the safety and tolerability of ARNI by studying adverse effects such as hypotension, elevated serum creatinine (Cr), and potassium (K
+
). A pooled effect size was calculated based on mean differences (MD) or log odds ratio (LogOR).

Results:
Our meta-analysis included 14 studies with a total of 305 patients, aged 25 to 84 (median 42 years) (
Table
). Among 305 ACHD patients, 70% had systemic RV, 27% had systemic LV, and 3% were Fontan patients with unknown ventricular morphology. When ARNI replaced ACEIs/ARBs and was added to remaining therapies, the pooled analysis indicated that ARNI significantly improved NYHA FC (LogOR: 0.67, 95% confidence interval (CI) 0.15-1.19, p=0.01) (
Figure 1A
). However, there was no significant change in ventricular function (logOR: 0.37, 95% CI 0.45-0.42, p=0.38). Notably, ARNI use led to a significant decrease in systolic blood pressure (MD=0.49, 95% CI -0.70 to -0.29, p=0.00) (
Figure 1B
), and elevated Cr levels (MD = 0.30, 95% CI 0.10-0.45, p=0.00) (
Figure 1C
). No significant change in K
+
level (MD=0.0, 95% CI -0.61 to 0.61; p=0.99) (
Figure 1D
). Eighteen patients (6%) discontinued ARNI due to side effects.

Conclusion:
Our meta-analysis found that ARNI replacement for ACEIs/ARBs improved NYHA FC in most ACHD HF patients across a heterogeneous group of ACHD HF patients consisting of single ventricle, systemic- RV and LV. However, there was no significant change in ventricular function or natriuretic peptide levels. Hypotension and increased serum Cr are more frequent with ARNI use, warranting close monitoring. Future research is needed to assess composite outcomes, including hospitalizations and mortality in ACHD HF patients after adding ARNI to conventional therapy.
Abstract 4143326: Multicomponent Digital Therapies to Promote Healthy Eating and Physical Activity and Reduce Risk Factors for Cardiovascular Disease in Older Adults: A Pilot Study
Authors: Cacciata Marysol , Candelaria Dion , Reyes Andrew Thomas , Serafica Reimund , Hildebrand Janett , Sta. Maria Axel , Lee Jung-Ah , Stromberg Anna , Evangelista Lorraine
Published: November 2024

Background:
Digital health technologies can promote healthy lifestyle behaviors. They can help patients identify, treat, and self-care for chronic illnesses, promote healthy aging, and minimize disparities through primary prevention. However, there is limited research on the efficacy of these systems in promoting healthy eating and physical activity and improving clinical outcomes among older adults at risk for cardiovascular disease.

Aims:
This pilot study aimed to (1) evaluate the feasibility of the study protocol for indicators of process (e.g., recruitment, consent, retention rates, engagement), resources (e.g., participant adherence, data collection time), and program safety (e.g., number of adverse events); and (2) compare changes in eating patterns, physical activity, and clinical outcomes (weight, blood pressure, lipid profile, and hemoglobin A1C [HbA1C]) between participants randomized to
Get FIT
vs.
Get FIT+
at baseline (pre-intervention) and 12 weeks (post-intervention).

Methods:
Fifty-four older adults (65.6 ± 5.8 years, 61% females, 61% married, 50% Asians, 6% Whites, 33% Hispanics, 11% Blacks) were randomized to
Get FIT
(n=24), which included one in-person behavioral counseling session on healthy eating and exercise, a participant handbook, an activity tracker (Fitbit Charge), and access to a nutrition app (MyFitnessPal) for 12 weeks, or
Get Fit+
(n=30), which included weekly personalized text messages to motivate and encourage participants to meet their weekly goals in addition to all the other components offered to participants in
Get FIT
.

Results:
All feasibility metrics were highly satisfactory, with consent and retention rates being 100% at 12 weeks. Both groups increased moderate to vigorous physical activity levels and decreased calorie intake over time. Participants in
Get FIT+
showed a 6% reduction in weight compared to less than 1% in the
Get FIT group
. All participants showed improvements in blood pressure levels, lipid profiles, and HbA1C, but improvements in HDL cholesterol and triglyceride levels were more prominent in the
Get FIT+
group.

Conclusion:
Our findings suggest that the
Get FIT+
intervention may help encourage healthy eating and physical activity among older adults while lowering their cardiometabolic risk. A large randomized clinical trial is needed to evaluate the efficacy of multicomponent digital health therapies in older adults at risk for cardiovascular disease.
Abstract 4143330: Pediatric Paracorporeal VAD Antiplatelet Protocol
Authors: Garg Ashish , Bercovitz Rachel , Hammond Nora , Monge Michael , Thrush Philip , Joong Anna
Published: November 2024

Background:
Ischemic stroke remains a dreaded complication of paracorporeal (continuous-PC; pulsatile-PP) ventricular assist devices (VADs) in pediatric patients. Advancements in anticoagulation management have improved the stroke rate to 12-17%, however, the management of antiplatelet therapy varies across centers. This study examines the outcomes of an antiplatelet protocol for patients with paracorporeal VADs at our center.

Methods:
We developed an antiplatelet protocol (Fig. 1) with dose adjustments guided by platelet function assays, VAD fibrin burden, and bleeding risk. We retrospectively reviewed patients with a paracorporeal VAD between December 2018 to December 2023. Demographic variables, incidence of thrombotic and bleeding events, and outcomes were assessed using descriptive statistics.

Results:
The cohort comprised 44 patients (52% male), median age 19 months (1 month - 8 years), with 22 (50%), 9 (20.5%), and 13 (29.5%) patients supported on PP, PC, and multiple VAD types respectively. Median support duration was 131 (PP; IQR 87, 183), 31 (PC; IQR 16, 46), and 88 (multiple VADs; IQR 66, 196) days. Diagnoses included cardiomyopathy 38% (n=17), congenital heart disease 57% (n=25) and others 5% (n=2). Thrombotic complications included: ischemic stroke in 6.8% (n=3) (1.9 events/100 patient months compared to 6-11 events/100 months reported in recent multicenter registry data); 11% (n=5) patients underwent 6 pump exchanges for fibrin burden. Major bleeding rate was 29.5% (n=13), most commonly gastrointestinal bleed; there were no hemorrhagic strokes. Five (11.3%) patients had an asymptomatic subdural hematoma (n=4 tiny/small, n=1 moderate). A positive clinical outcome was achieved in 86%, with 77% (n=34) bridged to transplant, 5% (n=2) explanted for recovery, and 5% (n=2) alive on device. Overall mortality was 14% (2 died on device, 4 transitioned to ECMO and died).

Conclusions:
Our experience underscores the efficacy of a structured antiplatelet protocol in managing pediatric patients with paracorporeal VADs associated with a low stroke rate. Future studies are needed to assess the generalizability of these findings.
Abstract 4143361: Digoxin ameliorates endothelial senescence, restores functional endothelial-subcutaneous adipocyte crosstalk and enhances glucose homeostasis in type 2 diabetes mellitus
Authors: Brown Oliver , Bridge Katherine , Luk Cheukyau , Straw Sam , Makava Natallia , Wijayagoonawardana Pradeep , Tayebjee Muzahir , Saunderson Christopher , Drozd Michael , Bruns Alexander-Francisco , Haywood Natalie , Witte Klaus , Gierula John , Wheatcroft Stephen , Cubbon Richard , Kearney Mark
Published: November 2024

Background:
Normal subcutaneous adipose tissue (SAT) function is dependent on healthy endothelial function and microvascular expansion. In type 2 diabetes mellitus (DM) and heart failure (HF) this becomes synergistically dysregulated, resulting in inflamed, fibrotic and metabolically dysfunctional SAT and may drive HF progression in DM. Hyperinsulinemia is associated with adipocyte senescence, however the role of endothelial senescence in SAT and its therapeutic potential is unknown.

Aims:
We examine the presence and sequelae of SAT microvascular endothelial cell (SATMVEC) senescence and its effects on adipocyte function in people with DM. Next, we examine the therapeutic role of digoxin at targeting SATMVEC senescence, modulating SATMVEC-adipocyte crosstalk and restoring metabolic homeostasis.

Methods:
We took pectoral SAT biopsies from 59 patients with HF undergoing pacemaker implant of whom 25 (42%) had DM (HFDM). SATMVEC were isolated from SAT, treated with 1ng/mL digoxin vs control for 24 hours and then characterised for functional senescence. Crosstalk between SATMVEC and subcutaneous white adipocytes from a single healthy donor were examined using co-culture (Fig 1A). Paired digoxin
vs
control treated SATMVEC were co-cultured with adipocytes for 24 hours. Adipocyte health was assessed using 2-NBD-glucose uptake, RNA and protein expression.

Results:
Isolated SATMVEC from patients with HFDM had a senescent phenotype with increased senescence associated secretory phenotype (SASP) and senescence associated ß-gal expression (p<0.05), reduced ATP production, proliferative capacity, and impaired angiogenesis (p<0.05). Adipocytes co-cultured with SATMVEC from patients with HFDM had increased expression of IL-6 (Fig 1B) and reduced 2-NBD-glucose uptake (p<0.05). Treatment of SATMVEC with digoxin reduced SATMVEC senescence (Fig 1C), increased adipocyte 2-NBD-glucose uptake (Figure 1D) and reduced IL-6 expression (p<0.01).

Conclusions:
SATMVEC from patients with HFDM are senescent and when co-cultured with adipocytes, results in a proinflammatory adipocyte phenotype resistant to glucose uptake. Digoxin reduces SATMVEC senescence, restores adipocyte glucose homeostasis and may repair dysfunctional SAT in patients with HFDM.
Abstract 4143368: Glycosphingolipid-Mediated Peripheral Immune Cell Inflammatory Activation Impairs Cardiomyocyte Function in Hypoplastic Left Heart Syndrome
Authors: Turner Mary , Pietra Ashley , Ramaswamy Praveen , Garcia Anastacia
Published: November 2024

Introduction:
Hypoplastic Left Heart Syndrome (HLHS) is the leading indication for heart transplant and the most common cause of cardiovascular death in infants, yet our understanding of the immunologic alterations in HLHS is inadequate. In this study we aimed to (1) assess whether peripheral blood immune cells (PBMCs) from HLHS patients display a pro-inflammatory phenotype, (2) identify specific factors associated with inflammation in HLHS, and (3) investigate the interaction between HLHS PBMCs and cardiomyocytes.

Methods:
PBMCs were isolated from whole blood by density gradient centrifugation and gene expression changes were assessed using next-generation RNA-sequencing. Mass-spectrometry was used to quantify PBMC lipid species. Healthy PBMCs were cultured with liposomes containing 10μM lactosylceramide (LacCer) and conditioned media (CM) was collected. Cytokine arrays were used to quantify LacCer-mediated inflammatory changes. Cardiomyocytes were treated with CM and mitochondrial bioenergetics were assessed using the Seahorse Bioanalyzer.

Results:
PBMCs from HLHS patients display significant enrichment of pathways associated with immune cell activation, and cytokine signaling that are suggestive of a pro-inflammatory phenotype. Glycosphingolipids (GSLs) are one of the most abundant glycolipids in humans and play an important role in immune cell signaling and function. We identified that the GSL, LacCer, is significantly enriched in HLHS PBMCs and that exogenous LacCer treatment of healthy PBMCs induces secretion of proinflammatory mediators (e.g., VCAM1, IL-8, CD14). Additionally,
in vitro
assays determined that CM from healthy PBMCs treated with LacCer is sufficient to promote mitochondrial dysfunction in primary cardiomyocytes.

Conclusions:
These data suggest that immune cells in HLHS display a pro-inflammatory phenotype that is mediated, at least in part, by increased LacCer. Further, these data provide insight into LacCer’s role in paracrine-mediated crosstalk between immune cells and cardiomyocytes in the setting of HLHS. This suggests a novel role for LacCer-rich PBMCs to potentiate progressive cardiac dysfunction in HLHS and provide an avenue for therapeutic intervention in this vulnerable population.
Abstract 4143372: Outcomes following the development and implementation of a multi-component, multidisciplinary cardiogenic shock program
Authors: Hill Morgan , Carnicelli Anthony , Yourshaw Jeffrey , Houston Brian , Witer Lucas , McMurray Jeffrey , Dodson Kaylen , Bull Lindsey , Hajj Jennifer , Summer Mary , Kilic Arman
Published: November 2024

Background:
Cardiogenic shock is associated with significant morbidity and mortality, necessitating a multidisciplinary approach to achieve optimal outcomes.

Aims:
This study evaluated the impact of a multi-component, multidisciplinary cardiogenic shock program on clinical outcomes.

Methods:
In 2021, we initiated a cardiogenic shock program incorporating several key components: monthly meetings within the entirety of the heart and vascular service line for patient review and dissemination of protocols and initiatives; formation of a core leadership group comprising representatives from cardiac surgery, heart failure, interventional cardiology, cardiac intensivists, and shock nursing coordinators; implementation of a shock paging system for real-time multidisciplinary discussions; appointment of two nursing coordinators for protocol development, education, and data tracking; development of a temporary MCS quality scorecard; and establishment of a program to transition Impella patients to a stepdown unit for bed optimization. Patient outcomes were compared between the inaugural year and the subsequent year of the shock program.

Results:
143 patients in cardiogenic shock were activated through our shock paging system during the study period. Patient age averaged 54.5 years. 51.1% of patients were located at our institution and 48.9% were located at an outside hospital upon shock call initiation. The most common etiology for shock was decompensated HF (33.6%), followed by acute MI (25.2%), arrhythmia (14%), and other (27.3%). The majority of patients presented with a SCAI shock stage of C (41.3%), followed by D (25.9%) and E (20.3%). 78.3% of patients received an MCS device as a result of the shock call, with 33.6% receiving an Impella CP, 16.8% receiving an Impella 5.5, 29.4% receiving an IABP, and 27.3% requiring VA ECMO. Prior to the shock team initiation, historical hospital survival rates in cardiogenic shock patients approached 30% at our institution. After initiation of the shock program, survival to hospital discharge improved to 67.8% and 1-year survival was 53.2%. 30-day survival improved in the second year of the program compared to the inaugural year (70.1% vs. 53.6%, p=0.0447).

Conclusion:
Implementation of a multi-component multidisciplinary shock program facilitates a systematic approach to cardiogenic shock and is associated with improved hospital culture and collaboration and excellent outcomes in a challenging patient subset.