bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 4112591: Delayed Migration of a Valve-in-Valve Transcatheter Aortic Valve Replacement
Authors: Baggett Katelyn , Kaleta Francois , Burmeister Cameron , Jain Sandeep , Kozak Mark , Nudy Matthew
Published: November 2024

Introduction:
Migration of a transcatheter aortic valve replacement (TAVR) is a rare, life-threatening complication that typically occurs during or shortly after the procedure. We present a unique case of an exceptionally rare, delayed migration of a valve-in-valve TAVR three years post-procedure that was subsequently treated with surgical explantation of the TAVR prosthesis and surgical aortic valve replacement (SAVR).

Clinical Case:
A 64-year-old male presented to an outpatient cardiology visit with one month of exertional dyspnea and near-syncopal episodes with a new diastolic murmur. Notable history included aortic regurgitation due to bicuspid aortic valve resulting in subcoronary implantation of a 27 mm Medtronic Freestyle stentless porcine bioprosthesis 20 years prior to presentation. Following the development of severe bioprosthetic regurgitation, a valve-in-valve TAVR with a 26 mm Edwards SAPIEN 3 Ultra was implanted 3 years prior to presentation with no evidence of stenosis or regurgitation on transthoracic echocardiograms completed 1 month and 1 year after implantation. Transesophageal echocardiogram now demonstrated migration of the TAVR valve into the left ventricular outflow tract 2 cm proximal to the surgical bioprosthesis. Severe eccentric transvalvular regurgitant flow through the surgical bioprosthesis and severe paravalvular regurgitation around the TAVR valve was seen with an unstable “rocking appearance”. No evidence of abscess or endocarditis was appreciated and blood cultures showed no growth. Following a short hospitalization, the patient underwent TAVR explantation and implantation of a 25 mm Edwards Inspiris Resilia stented bovine bioprosthesis with subsequent resolution of his symptoms.

Discussion:
Recognizing atypical presentations of TAVR complications such as delayed valve migration is facilitated by understanding key risk factors. This case highlights notable risk factors for TAVR migration including a valve-in-valve TAVR over a degenerative regurgitant bioprosthesis, decreased aortic annulus calcification resulting in suboptimal anchoring, the patient’s younger age, and the lack of a radiopaque marker on the stentless bioprosthesis which increases the potential for malpositioning.
Abstract 4112853: Trends in Statin Use for the Secondary Prevention of Atherosclerotic Cardiovascular Disease among U.S. Adults by Age, 1999-2020
Authors: Junwen Wang , YE Yuyang , CHEN Xuefeng , HU Xinru , PENG Yong
Published: November 2024

Background:
Current research focusing on trends in statin medication usage, particularly for different age groups, is limited. This study explored the change trends in statin usage from 1999 to 2020, with a specific focus on different age groups.

Methods:
Utilizing data from the National Health and Nutrition Examination Survey spanning the period from 1999 to 2020, our study included individuals aged 18 years and older diagnosed with atherosclerotic cardiovascular disease (ASCVD).

Results:
In the 18-44 years age group, usage changed from 18.34% (95% CI, 0.18 to 36.50) in 1999 to 16.63% (95% CI, 0.36 to 32.91) in 2020 (linear P value = 0.540, quadratic P value = 0.610) (Figure 1). For individuals aged 45-64 years, usage increased from 39.33% (95% CI, 29.62 to 49.05) in 1999 to 54.97% (95% CI, 47.10 to 662.83) in 2020 (linear P value < 0.001, quadratic P value = 0.777) (Figure 1). In the group aged 65 years and older, usage increased from 35.17% (95% CI, 29.57 to 40.77) in 1999 to 60.62% (95% CI, 55.73 to 65.51) in 2010, and further to 68.62% (95% CI, 63.65 to 73.60) in 2020 (quadratic P value < 0.001) (Figure 1). There was an interaction effect between statin usage trends and age (P for interaction <0.001) (Figure 1).

Conclusion:
Overall, current health policies are effective for the use of statins for the secondary prevention of ASCVD. However, there was almost no improvement in statin usage within the 18-44 years age group. This highlights the need for greater focus on young ASCVD patients. Therefore, additional research is needed on statin use among young people.
Abstract 4113047: Discovering novel biomarkers and predicting cardiovascular disease using AI/ML techniques for precision medicine
Authors: Ahmed Zeeshan
Published: November 2024

Personalized interventions are deemed vital given the intricate characteristics, advancement, inherent genetic composition, and diversity of cardiovascular diseases (CVDs). The appropriate utilization of artificial intelligence (AI) and machine learning (ML) methodologies can yield novel understandings of CVDs, enabling improved personalized treatments through predictive analysis and deep phenotyping. In this study, we proposed and employed a novel approach combining traditional statistics and a nexus of cutting-edge AI/ML techniques to identify significant biomarkers for our predictive engine by analyzing the complete transcriptome of CVD patients (Figure 1). After robust gene expression data pre-processing, we utilized three statistical tests to assess the differences in transcriptomic expression and clinical characteristics between healthy individuals and CVD patients. Next, a classifier assigned rankings to transcriptomic features based on their relation to the case-control variable. The top ten percent of commonly observed significant biomarkers were evaluated using four unique ML classifiers. After optimizing hyperparameters, the ensembled models, which were implemented using a soft voting classifier, accurately differentiated between patients and healthy individuals. We have uncovered 18 transcriptomic biomarkers that are highly significant in the CVD population that were used to predict disease with up to 96% accuracy (Figure 2). Additionally, we cross-validated our results with clinical records collected from patients in our cohort (Figure 3). The identified biomarkers served as potential indicators for early detection of CVDs. With its successful implementation, our newly developed predictive engine provides a valuable framework for identifying patients with CVDs based on their biomarker profiles.
Abstract 4113147: Global Longitudinal Strain in Patients with Coronary Microvascular Dysfunction
Authors: Merdler Ilan , Sadeghpour Anita , Asch Federico , Case Brian , Zhang Cheng , Hill Andrew , Lupu Lior , Chitturi Kalyan , Hashim Hayder , Waksman Ron
Published: November 2024

Background:
Angina in the absence of obstructive coronary artery disease (ANOCA) is a common but undertreated condition due to poorly understood pathophysiologic mechanisms. This study investigates the potential link between ANOCA and left ventricular (LV) dysfunction, specifically focusing on coronary microvascular dysfunction (CMD) as a contributing factor.

Methods:
Registry patients diagnosed with CMD, were compared with those without CMD. Echocardiographic analysis, including global longitudinal strain (GLS), was conducted using advanced software aided by human expertise. Out of 281 patients, 121 had echocardiograms accessible in our systems for review. After excluding patients with echocardiograms of low technical quality, those with cardiomyopathies, or a history of myocardial ischemia, we identified 21 patients with CMD and 38 without CMD.

Results:
The mean age of the entire cohort was 59.5±11.5 years, with 76.7% being female. The prevalence of hypertension and hyperlipidemia was 71.2% and 67.8%, respectively, while 23.7% had diabetes. More than half of the patients had a CCS angina score of 2 (59.3%). There were no differences in medication usage during catheterization between the two groups concerning beta-blockers, nitrates, calcium channel blockers, and diuretics. No discrepancies were observed between the two groups in LVEF (overall mean of 62±8), LV mass, ventricle and atrium sizes and measurements, diastolic function, and other commonly used and reported echocardiographic variables. Despite initial hypotheses suggesting CMD-related alterations in LV mechanical function, no significant differences in GLS were observed between CMD-positive and CMD-negative groups.

Conclusion:
Our findings, although inconclusive, underscore the need for further large-scale investigations integrating comprehensive echocardiographic assessments to elucidate the complex interplay between CMD and LV mechanical function.
Abstract 4113371: Impact of Protein-Energy Malnutrition on Atrial Fibrillation Outcomes: Insights from National Inpatient Sample (NIS) Study
Authors: Upreti Prakash , Neupane Binita , Karki Sunita , Prasai Astha , Karki Roshan , Rao Mohan , Aronow Wilbert , Tamirisa Kamala
Published: November 2024

Background:
Atrial fibrillation (AF) is the most prevalent arrhythmia. Protein-energy malnutrition (PEM) has been implicated in various cardiovascular conditions, but the studies on its impact on AF outcomes are limited. This study aims to investigate the relationship between PEM and AF outcomes, since malnutrition could be a modifiable risk factor.

Methods:
Utilizing data from NIS (2017–2020), patients of age more than 18 years with a primary diagnosis of AF and a secondary diagnosis of PEM were identified. Data analysis was performed using STATA, employing the Student's t-test and Fischer's exact test to compare continuous variables and proportions, respectively. Adjusted odds ratios were calculated through multivariate regression analysis. The primary outcome was mortality, with secondary outcomes being mean length of stay (LOS), total hospitalization cost, major adverse cardiovascular events (MACE) and various in-hospital complications. Trends in mortality, LOS, and total cost of hospitalization were also assessed.

Results:
A total of 17,652,695 patients with AF were identified, of whom 1,452,695 (8.22%) had PEM. Patients with PEM had increased mortality (10.8% vs 4.52%, p<0.001), increased mean LOS (10.14 days vs 5.52 days, p<0.001) and a higher hospitalization cost ($121,721 vs 69,348, p<0.001). In AF patients with PEM compared to those without PEM, there were significantly increased rates of ACS (adjusted odds ratio, or aOR=1.21, 2.48 vs 1.85, p<0.001), pulmonary edema (aOR=1.37, 0.61 vs 0.44, p<0.001), CVA (aOR=1.45, 1.7 vs 1.04, p<0.001) acute respiratory failure (aOR=1.78, 20.27 vs 11.75, p<0.001), need of mechanical ventilation (aOR= 2.46, 9.36 vs 3.96, p<0.001), ARDS (aOR= 2.8, 0.55 vs 0.21, p<0.001), AKI (aOR=1.57, 35.45 vs 24.12, p<0.001), and septic shock (aOR= 3.32, 10.3 vs 3.24, p<0.001). There is an increased trend of mortality (10.77 in 2017 vs 11.87 in 2020, p<0.001), LOS (10.49 in 2017 vs 10.8 in 2020, p=0.04) and total hospitalization cost ($121,233 in 2017 vs $140,869 in 2020, p<0.001) in patients with AF and PEM.

Conclusion:
Our study highlights the association between PEM and adverse AF outcomes, revealing PEM as a significant predictor of increased mortality, morbidity, length of stay, and hospitalization costs. These results emphasize the necessity for targeted nutritional interventions in AF management. Further research and clinical strategies addressing nutritional deficits in AF populations are essential for improving outcomes.
Abstract 4113494: Gut Microbiota Modulation by Immunosuppression and Cardiac Cell Therapy in a Nonhuman Primate Ischemia/Reperfusion Model of Cardiac Regeneration
Authors: Hsieh Patrick
Published: November 2024

End-stage ischemic heart disease necessitates heart transplantation, and emerging cell therapy presents a promising solution to address donor scarcity. Disruption of gut microbiota significantly influences various diseases and treatments, including transplantation. However, the impact of immunosuppression and cardiac cell therapy on gut microbiota remains largely unexplored. To elucidate this relationship, we investigated gut microbiota dynamics in response to immunosuppression and cell therapy in a nonhuman primate (NHP) cardiac ischemia/reperfusion (IR) model, with controlled genetic, dietary, and environmental factors. Immunosuppression enriched anaerobes (Faecalibacterium, Streptococcus, Anaerovibrio, Dialister), increasing gut microbiota diversity. These changes correlated with metabolic shifts towards amino acid metabolism and nucleosides/nucleotides biosynthesis. Combined treatment of human induced pluripotent stem cell (iPSC)-derived endothelial cells (EC) and cardiomyocytes (CM) also increased gut microbiota diversity, with specific genera alterations. The EC/CM co-treatment group displayed gut microbiota resembling the pre-injury group, with host metabolism shifting towards amino acid and fatty acid/lipid biosynthesis post-cell therapy. These observed microbiota changes and metabolic shifts could serve as biomarkers for monitoring cell therapy and immunosuppression outcomes, offering potential therapeutic targets to enhance efficacy.
Abstract 4113561: Efficacy and Outcomes of Empagliflozin in Acute Coronary Syndrome Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Jain Hritvik , Odat Ramez , Goyal Aman , Jain Jyoti , Rathore Sawai Singh , Patel Nandan , Pervez Neha , Passey Siddhant , Saleem Maryam , Suleiman Hassan
Published: November 2024

Background:
Sodium-glucose co-transporter 2 inhibitors (SGLT2i) have demonstrated mortality benefits in patients with heart failure (HF). Since acute coronary syndrome (ACS) is an increasingly prevalent cardiovascular condition that often leads to HF, SGLT2i might play a role in reducing mortality in these patients. Previous randomized controlled trials (RCTs) have demonstrated inconsistent efficacy of Empagliflozin, an SGLT2i, in patients with ACS.

Methods:
A comprehensive systematic literature search was conducted spanning the major bibliographic databases to retrieve RCTs comparing Empagliflozin to placebo in patients with ACS. Odds ratios (OR) and mean differences (MD) with 95% confidence intervals were pooled using the DerSimonian and Laird random-effects model with statistical significance set at p<0.05.

Results:
5 RCTs were included with 7229 ACS patients (3608 in the Empagliflozin group and 3621 in the placebo group). Empagliflozin treatment was not associated with a statistically significant difference in all-cause mortality [OR: 0.94; 95% CI: 0.76, 1.17; p=0.60], cardiovascular death [OR: 1.00; 95% CI: 0.79, 1.28; p=0.99], hospitalization for heart failure [OR: 0.86; 95% CI: 0.42, 1.74; p=0.67], serious adverse events [OR: 1.85; 95% CI: 0.29, 11.87; p=0.51], LVEF on follow-up [MD: 4.35; 95% CI: -4.52, 13.23; p=0.34], NT-ProBNP [MD: -126.02; 95% CI: -279.37, 27.32; p=0.11], estimated glomerular filtration rate [MD: 1.59; 95% CI: -1.35, 4.52; p=0.29], and HbA1c [MD: -0.17; 95% CI: -0.53, 0.20; p=0.38] compared to placebo.

Conclusion:
This study concludes no statistical difference in all-cause mortality, cardiovascular death, and hospitalization for heart failure with empagliflozin therapy in ACS patients compared to placebo, however, the largest study (EMPACT-MI) had a statistically significant difference in hospitalizations for HF. Further large multicentric RCTs are warranted to validate these findings.
Abstract 4113885: Impact of Sodium-glucose Cotransporter 2 Inhibitor on Recurrence and Cardiovascular Outcomes after Catheter Ablation for Atrial Fibrillation in Patients with Heart Failure
Authors: Zhao Joey , Jiang Chao , Kong Xiangyi , HE liu , Jiang Chen-Xi , Sang Caihua , Long Deyong , Dong jz , Ma Changsheng
Published: November 2024

Background:
Catheter ablation for Atrial fibrillation (AF) has been proven to improve the prognosis in patients with heart failure (HF), while it remains a high risk for AF recurrence and adverse cardiovascular outcomes. The impact of sodium-glucose cotransporter 2 inhibitors (SGLT2i) on these outcomes in HF patients after AF ablation is unknown.

Method:
HF patients with AF undergoing catheter ablation between January 2017 and December 2022 from the China-AF Registry were included. Patients were stratified into 2 groups based on the use of SGLT2i at discharge and were 1:1 matched by propensity score, with SGLT2i using (n=368) and non-SGLT2i using (n=368) in each group. The primary outcome was AF recurrence after a 3-month blanking period.

Results:
During a total of 1315 person-year follow-ups, AF recurrence occurred in 83 patients (22.6%) in the SGLT2i group and 132 patients (35.8%) in the non-SGLT2i group. SGLT2i was associated with a lower risk of AF recurrence (adjusted HR = 0.56, 95% CI: 0.43-0.74, P<0.001). The composite risk of cardiovascular death, thrombotic events, or cardiovascular hospitalization was significantly lower in the SGLT2i group compared with those without SGLT2i (adjusted HR = 0.58, 95%CI: 0.41-0.80, p = 0.001). Although there was a tendency towards benefits, significant differences in all-cause mortality (adjusted HR = 0.76, 95%CI: 0.35-1.63, p = 0.480), cardiovascular mortality (adjusted HR = 0.62, 95%CI: 0.24-1.57, p = 0.312) and thrombotic events (adjusted HR = 0.40, 95%CI: 0.16-1.03, p = 0.056) were not noted between groups.

Conclusion:
The use of SGLT2i was associated with a lower risk of AF recurrence and the composite outcome of cardiovascular death, thrombotic events, or cardiovascular hospitalization after catheter ablation for AF in patients with HF.
Abstract 4113890: Impact of blood pressure management on cardiovascular events among patients with familial hypercholesterolemia
Authors: Tada Hayato , Takeji Yasuaki , Nohara Atsushi , Kawashiri Masa-aki , Takamura Masayuki
Published: November 2024

Background:
Hypertension status has been associated with worse outcomes among patients with familial hypercholesterolemia (FH). We aimed to determine clinical impact of management of blood pressure in development of major adverse cardiovascular events (MACE).

Methods:
Patients with clinically diagnosed heterozygous FH (HeFH) (N=1,273, male/female=614/659) with blood pressure data were assessed. We divided the patients into 4 groups (group 1: patients without hypertension from baseline to their follow-up, group 2: patients without hypertension at baseline, but developed hypertension at follow-up, group 3: patients with hypertension at baseline, but well-controlled at follow-up, group 4: patients with hypertension from baseline and uncontrolled at their follow-up). Cox proportional hazards models were used to assess factors associated with MACE, including cardiovascular death and any coronary events.

Results:
The median follow-up period was 10.9 years. During the follow-up period, 142 MACEs were observed. We found that the management of blood pressure was significantly associated with the occurrence of MACE (hazard ratio (HR): 2.50; 95% confidence interval (CI): 1.30–3.70; p<0.001, HR: 4.18; 95% CI: 2.08–6.28; p<0.001, HR: 10.96; 95% CI: 6.10–17.58; p<0.001, in group 2, group 3, and group 4, respectively when group 1 was considered as reference).

Conclusions:
Blood pressure management appears to be very important among patients with HeFH.
Abstract 4113997: Semaglutide Improves Myocardial Perfusion and Performance in a Large Animal Model of Coronary Artery Disease
Authors: Stone Christopher , Harris Dwight , Broadwin Mark , Kanuparthy Meghamsh , Yalamanchili Keertana , Nho Ju-Woo , Abid Ruhul , Sellke Frank
Published: November 2024

Background:
Coronary artery disease (CAD) is the leading cause of death worldwide. It imposes an enormous symptomatic burden on patients, leaving many with residual disease despite optimal procedural therapy, and up to 1/3
rd
with debilitating angina amenable neither to procedures, nor to current pharmacologic options. Semaglutide, a glucagon-like peptide 1 agonist originally approved for management of diabetes, has garnered substantial attention for its capacity to attenuate cardiovascular risk. Although subgroup analyses in patients indicate promise, studies explicitly designed to isolate the impact of semaglutide on the sequelae of CAD are lacking.

Methods:
Yorkshire swine (n=17) underwent placement of an ameroid constrictor around the left circumflex coronary artery to induce CAD. Oral semaglutide was initiated postoperatively at 1.5 mg and scaled up in 2 weeks to 3 mg in treatment animals (SEM, n=8) for a total of 5 weeks, while control animals (CON, n=9) received no drug. All then underwent myocardial harvest with acquisition of perfusion and functional data using microsphere injection and pressure-volume loop catheterization. Immunoblotting, immunohistochemistry, and immunofluorescence were performed on the most ischemic myocardial segments for mechanistic elucidation.

Results:
SEM animals exhibited improved left ventricular ejection fraction, both at rest and during rapid myocardial pacing to 150 bpm (both p<0.03), accompanied by increased perfusion to the most ischemic myocardial region at rest and during rapid pacing (both p<0.03); reduced perivascular and interstitial fibrosis (both p <0.03); and apoptosis (p=0.008). These changes were associated with increased activation of the endothelial-protective AMPK pathway (p=0.005), coupled with downstream increases in endothelial nitric oxide synthase (p=0.014).

Conclusions:
This study is the first to reveal the capacity of oral semaglutide to augment cardiac function in the chronically ischemic heart in a highly translational large animal model, likely through AMPK-mediated improvement in endothelial function and perfusion to the ischemic myocardium.
Abstract 4114293: Impact of stent length on long-term clinical outcomes in acute myocardial infarction patients treated with second-generation drug-eluting stents
Authors: Choi Woonggil , Rha Seung-Woon , Choi Byoung Geol , Choi Se Yeon , Choi Cheol Ung , hyun sujin , Byun Jae Kyeong , Cha Jinah , Kim Sang Min , Bae Jang-whan , Hwang Kyung-Kuk , Kim Dong-Woon , Cho Myeong-Chan , Lee Ju-Hee , Bae Dae-Hwan , Kim Min , Lee junyoung , Sun jonghee
Published: November 2024

Background:
Stent length has been considered an important predictor of adverse events in stable patients undergoing percutaneous coronary intervention (PCI). However, there are few data in acute myocardial infarction (AMI) patients treated with very long drug-eluting stents (DES). We conducted this study to evaluate the impact of stent length on the long-term clinical outcomes.

Method:
The study included a total of 9,021 AMI patients who underwent PCI with 2
nd
generation DESs. The patients were categorized into 3 groups according to the stent length: group A (<38mm, n=6821), group B (38 – 59mm, n=1735) and group C (≥60mm, n=465) and compared using the inverse probability of treatment-weighted (IPTW) method. The primary outcome was the incidence of major adverse cardiac events (MACEs) up to 3years.

Results:
After adjustment for baseline differences, stent length was still significantly associated with higher cumulative rates of MACE [Odd ration(OR) :1.15 for 38 -59mm group, 95% confidence interval (CI): 1.06-1.26, p= 0.001, OR 1.23 for ≧ 60mm group, 95% CI: 1.13 -1.34, p< 0.001], especially, non-target vessel revascularization (TVR), not TVR, (table). In subgroup analysis, 3-year TVR according to stent length, Biolimus A9 stent was associated with TVR in patient with more than 38-59mm stent (OR 6.50, 95% CI: 2.60 to 16.26, p 〈 0.001).

Conclusion:
Even in the 2
nd
generation DES era, stent length was associated with adverse long-term clinical outcomes in patients with AMI. Interestingly, long stent implantation did not affect target vessel failure but non-TVR.
Abstract 4114308: Defective in LYPLA1-Mediated Lysophosphatidylcholine Metabolism Contributes to Diabetes-Induced Atherosclerosis and Subsequent Myocardial Dysfunction
Authors: Gao Bin , Zhao Xinyu , Yuan Meng , Zhang Lei , Chen Xiuzhu , Qin Qin , Dong Yuehua , Zhong Li , Guo Rui
Published: November 2024

Background and Objective:
Diabetes mellitus (DM) is a chronic metabolic condition that can cause serious damage to blood vessels and the heart. While current metabolomics research mainly focused on metabolic profiles during disease onset or at advanced stages, there remains a gap in understanding the molecular mechanisms of metabolites in the progression of diabetic cardiovascular disease. This study aims to explore effective strategies for preventing cardiovascular complications in diabetics by excavating metabolic pathways and mechanisms.

Methods:
Peripheral blood samples were obtained from 21 healthy individuals, 20 patients diagnosed with DM, 20 patients with coronary heart disease (CHD), and 25 patients with both DM and CHD (DC). Cardiac function, biochemical parameters and serum metabolome were detected. A specialized methodology with rigorous screening criteria was employed to identify differential metabolites associated with diabetes-induced CHD and cardiomyopathy. Mice were injected with LPC16:0 to assess cardiovascular function. Models of diabetes and diabetic atherosclerosis were induced by STZ injection and high-fat diet feeding in WT and ApoE
-/-
mice. Cardiac function and differential metabolites in aortic and cardiac tissues were assessed. The effect and molecular mechanism of LYPLA1 on vascular function, mitochondrial function, and metabolites-related enzymes were examined in human aortic endothelial cells (HAECs) and AC16 cardiomyocytes.

Results:
Cardiac function was markedly declined in DM and DC patients, as well as in mice with diabetes and diabetic atherosclerosis. However, CHD patients and atherosclerosis alone did not exhibit evident cardiac dysfunction. Key metabolites associated with diabetic cardiomyopathy and diabetes-induced CHD were identified as LPE18:1 and LPC16:0, respectively. Intraperitoneal administration of LPC16:0 in mice led to decreased LYPLA1, severe myocardial anomalies, and the appearance of plaques in the aortic arch. Either LYPLA1 knockdown or the treatment with high glucose and palmitic acid in HAECs resulted in impaired mitochondrial function, reduced intracellular NO and eNOS activity, which were mitigated by LYPLA1 overexpression.

Conclusion:
The metabolite LPC16:0 and the regulatory enzyme LYPLA1 are pivotal in driving the advancement of cardiovascular complications triggered by diabetes. Targeting LYPLA1 could represent a promising strategy for preventing diabetes-induced CHD and subsequent cardiomyopathy.
Abstract 4114497: Shape Variations in Right Ventricular 3D Geometry are associated with adverse outcomes in Hypoplastic Left Heart Syndrome Patients: A Fontan Outcomes Registry using CMR Examination (FORCE) Study
Authors: Loke Yue-Hin , O'Hara Ryan , Contento Jacqueline , Marella Nicole , Anantuni Lekha , Gaviria Susana , Kollar Sarah , Vegulla Ravi , Mehta Rittal , Balaras Elias , D'UDEKEM YVES , Alsaied Tarek , Olivieri Laura , Truong Uyen , Capuano Francesco
Published: November 2024

Introduction:
Right ventricular (RV) function is critical to the long-term health of patients with hypoplastic left heart syndrome (HLHS). However, conventional measurements do not consider the range of RV morphology that may impact RV function and lead to adverse outcomes. In this study, we determined associations between RV shape and clinical outcomes of HLHS using statistical shape modeling (SSM) and a large cardiac magnetic resonance (CMR) multicenter registry.

Methods:
Three hundred and twenty-eight studies from unique HLHS patients in the
F
ontan
O
utcomes
R
egistry using
C
MR
E
xaminations (FORCE) were post-processed by a core lab at one institution, including volumetry and strain analysis. 3D end-diastolic models of RV were reconstructed using Mimics (Materialise). SSM was performed via Shapeworks Studio (NIH/NIGMS CIBC) to derive mean template and quantified shape variations (shape mode) representing deviation from the mean. RV shape relationship with mortality/heart transplant was assessed using bivariable/multivariable analyses with stepwise model selection.

Results:
The mean template from all 328 patients resembled a circumferentially dilated RV with loss of concavity in septal wall (Fig A). Several generalized variants were identified (Fig B), particularly p1 – a sigmoidal / “apical bulge” variant where the RV apex dilates and "wraps” around the hypoplastic left ventricle (Fig C). Twenty-eight patients (8.5%) experienced mortality/heart transplant at 2.5±2.4 years after CMR. On bivariable analysis, p1 was associated with mortality/heart transplant, along with larger indexed RV end-diastolic volume/mass and reduced global circumferential strain. On multivariable analysis, p1 and indexed RV mass were associated with mortality/heart transplant (Table).

Conclusions:
Statistical Shape Modeling can define the “usual” RV shape of HLHS. A sigmoidal shape variant is associated with adverse outcomes. SSM may provide patient-specific metrics to define RV dysfunction in HLHS.
Abstract 4115139: The Clinic Ottakring – Lipid Registry: a Contemporary Single-Center Real-World Analysis from a Tertiary Hospital
Authors: Weltler Patrick , Pogran Edita , Harbich Paul Felix , Burger Achim , Neubauer Georg , Huber Kurt
Published: November 2024

In the real world only about 20 % of patients with ASCVD are at the target range, as shown by the SANTORINI trial (1). Therefore, there is still a great need for the improvement of lipid-lowering therapy (LLT).

Our Lipid Registry was set up as a retrospective study including patients who visited our outpatients ward focusing on lipid-lowering therapy (LLT). The indications were: low-density lipoprotein cholesterol (LDL-c) > 130 mg/dL in LLT- naive patients with acute coronary syndrome (ACS), coronary artery disease (CAD) not on optimal LLT, familial hypercholesterolemia and LLT intolerance. We collected baseline characteristics as well as laboratory parameters of these patients during their visits. The dual LLT (high-potency statin and ezetimibe) was initiated in every patient during the hospitalization, if not contraindicated, as target variable we used non-HDL-C.

In total 181 patients were included, of which 136 (75.1%) patients visited our clinic for control purposes. Patients who didn’t visit the clinic were predominantly men and had no or few pre-experiences with LLT. Fourty-one (36.9%) patients had a BMI>30, 126 (92.6%) of patients had CAD of which 85 (63%) had the diagnosis of a recent ACS. Arterial hypertension was present in 78.7% and diabetes mellitus type 2 in 23.5% of cases. At the 1
st
visit to our LLT department 4-6 weeks after dismission from the hospital, 86 patients (61.9%) reached the recommended (ESC/EAS 2019) non-HDL-C goal. At the 2
nd
visit (8-12 weeks after index hospitalization), 117 patients (86.2%) and at the 3
rd
visit 120 patients (88.2%) reached their target. The analysis of patients initially presenting with ACS showed that 60 (69.8%) of them after 4-6 weeks and 77 (90.6%) patients after 8-12 weeks reached the recommended non-HDL-c goal. Among the study population 108 (79.4%) of patients, and 81 (95.3%) of ACS patients received dual LLT immediately during the index event. After the first visit, 31 (36.5%) of ACS patients needed the addition of the third lipid-lowering drug to achieve the recommended goal (see attached tables).

Our strategy for managing hyperlipidemia in patients with a very-high cardiovascular risk showed high achievement of the non-HDL-C goal as recommended by the recent ESC guidelines in contrast to real-world data. We were able to demonstrate, that the strategy based on the idea to treat high-CV risk patients early and strong is the way to reach the treatment goal in a high percentage of patients (2).
Abstract 4115231: Higher Global Registry of Acute Coronary Events Score is Associated with Lower Invasive Coronary Angiograpy Use
Authors: Slone Sarah , Meeks William , Barringhaus Kurt
Published: November 2024

Background:
Use of invasive coronary angiography (ICA) and the selection of other interventions in patients who present with NSTEMI should be guided by clinical risk stratification. National guidelines recommend ICA use in patients with intermediate and high risk scores. The Global Registry of Acute Coronary Events (GRACE) score is a commonly used risk score that is based on clinical characteristics available at the time of admission.

Aim:
Examine if patients with NSTEMI with higher risk stratification scores are more likely to have ICA.

Methods:
This cross-sectional study included all patients who presented with NSTEMI to an academic medical center that serves a rural population over a 12-month period. Data were derived from the American College of Cardiology Chest Pain – MI Registry data collected by trained abstractors at the facility and were verifed by the study team. Additional data needed to calculate the GRACE Score were abstracted by the study team. GRACE Scores were categorized into low (1-88), moderate (89-118), and high (119-263) risk. Multivariable logistic regression was used to test if higher GRACE scores are more associated with ICA use controlling for patient factors not included in the GRACE Score and further examined by GRACE score category.

Results:
The total sample size was 434 patients (Mean age 65±13.8, 36% female and 36% Black). Patients transferred from outlying facilities accounted for 40% of the sample. ICA was performed for 94% of the patients. Increasing GRACE score was associated with lower ICA use (aOR 0.98, 95% CI 0.97-0.99). Odds of ICA use between the low-risk group and the intermediate risk group (aOR 0.60, 95% CI 0.19-1.91) did not significantly differ. Patients in the high-risk category were less likely to undergo ICA compated to low-risk patients (aOR 0.22, 95% CI 0.07-0.62).

Conclusions:
Use of ICA decreased as GRACE score increased in this patient sample, suggesting that additional factors beyond GRACE score likely influence ICA use in patients who presented with NSTEMI during this time period. Influence of patient factors as well as provider and patient risk aversion on ICA selection must be explored to better understand incongruence with guideline recommendations.
Abstract 4115235: Disparities in Youth Cardiac Screening by Childhood Opportunity Index: Insights from the Heartbytes Database
Authors: Corsi Douglas , Saraiya Avinash , Veltre Vanessa , Qiu Grace , Doyle Margaret , O'Malley Blaise , Shah Vacha , Langstaff Renee , Masood Imran , Osler Brian , Hajduczok Alexander , Johnson Drew , Shipon David
Published: November 2024

Intro:
The AHA endorses screening youth athletes to identify risk for sudden cardiac arrest (SCA). Rates of SCA can be predicted by social determinants of health (SDOH) such as education level and proportion of Black residents in ZIP Code. The Child Opportunity Index (COI) quantifies neighborhood factors that influence health and development. The link between COI and youth cardiac screening findings and outcomes remains unclear.

Hypothesis:
Cardiac screening data will differ significantly by COI.

Aims:
To identify differences in cardiac screening data in children of varying COI.

Methods:
The HeartBytes Database, including sports exams, self-reported physical activity (PA), and zip codes from Simon's Heart screenings was augmented with COI index zip code data. Chi-squared and logistic regression were used to analyze demographics, cardiac risk factors, and screening results.

Data:
Screening data of 11,431 youth athletes (median age 14.3 (IQR = 3), BMI 20.6 (4.8), 53.7% male, 70.6% White) was analyzed. The majority of children had very high overall COI (Figure 1). Hypertension, hyperlipidemia, Kawasaki disease, and heart infection were similar across COI levels (p > 0.05). Levels of physical activity varied significantly across levels of overall COI, with the highest levels reported in the lowest COI group (50.4% with
>
10 hours PA/week) (Chi-Squared; p = 0.007). Positive screening rates varied significantly by level of COI (p = 0.013) (Figure 2). The overall level of education, health environment, and socioeconomic COI did not predict positive screening outcomes in logistic regression analysis (all p>0.05).

Conclusion:
Prevalence of cardiac risk factors did not vary significantly across COI levels, however, positive screening rates were highest in moderate and very low COI levels. Simon’s Heart engaged communities across the COI spectrum; however, a majority of children had high or very high COI. Further efforts are needed to expand access to underserved populations of lower COI.
Abstract 4115645: NLRP3 Inflammasome Inhibition With Dapansutrile in Type 2 Diabetes and Elevated Systemic Inflammation: Rationale and Design of the DAPAN-DIA study
Authors: Hepprich Matthias , Esser Nathalie , Julla Jean-Baptiste , Kahl Sabine , Herder Christian , Larger Etienne , Mallone Roberto , Venteclef Nicolas , Roden Michael , Potier Louis , Paquot Nicolas , Abbate Antonio , Noor Mustafa , dinarello charles , Gautier J-F , Donath Marc
Published: November 2024

Background:
Monoclonal antibodies against IL-1β decrease inflammation, improve insulin secretion and glycaemia, and reduce residual CV risk, but must be injected and are associated with higher incidence of fatal infection. There remains an unmet need for an oral treatment for T2D patients at risk for cardiometabolic complications to safely reduce IL-1β-mediated inflammation chronically&with low risk of immunosuppression. In an initial dose-range finding study in heart failure patients with T2D, we reported evidence of anti-hyperglycaemic efficacy and improvement in LVEF with dapansutrile an oral specific inhibitor of the NLRP3 inflammasome.

Objectives:
To investigate the potential of preventing the transition to organ complications, The EU funded consortium INTERCEPT-T2D in collaboration with US based biotech Olatec Therapeutics has launched a clinical trial of anti-inflammatory therapy with dapansutrile targeting T2D patients with low-grade inflammation.

Methods:
Dapansutrile in Diabetes and Complications (DAPAN-DIA, NCT06047262) aims to determine whether NLRP3 inhibition with dapansutrile has the potential to not only improve glycaemia but also reduce micro- and macro-vascular risk and complications from diabetes. DAPAN-DIA is a multicenter, pbo-controlled, prospective, randomized, double-blind trial conducted in Switzerland, France, Belgium and Germany. A total of 300 patients with T2D, HbA1c >7.5% and hsCRP>1.5 mg/L are being randomized to either dapansutrile 1000 mg BID or matching PBO tablets for 6 months (2:1 ratio dapansutrile: pbo). The primary endpoint is change from baseline HbA1c. Secondary endpoints include biomarkers associated with diabetic complications, progression of MASLD as well as chronic inflammation (IL-1 β, IL-6 and hsCRP). A subject-assessed QoL questionnaire is also collected.

To detect an absolute difference of 0.5% in HbA1c between groups, approximately 300 subjects will be randomized 2:1 ratio to achieve 80% power, assuming a standard deviation of 1.2% in change from baseline in HbA1c at week 26.

Results:
The trial has launched and currently is enrolling subjects.

Conclusions:
DAPAN-DIA is the first placebo-controlled, adequately powered, large, multi-center study with an oral NLRP3-specific Inhibitor, dapansutrile. The trial will generate important data on a new clinically relevant dimension in T2D care where consideration at diagnosis of inflammatory parameters are of importance for the transition to T2D-related complications.
Abstract 4115816: Enhancing Cardiogenic Shock Management: Insights from MCS utilization and Patient Outcomes
Authors: karki monika , Bhattarai Pramod , Mohan Riya , Reyna Yordanka
Published: November 2024

Cardiogenic shock (CS) remains a challenge with high mortality rates despite advances in treatment modalities. This study investigates the utilization and impact of mechanical circulatory support (MCS) devices, including intra-aortic balloon pump (IABP), Impella, and Extracorporeal Membrane Oxygenation (ECMO) on patient outcomes in CS management.

A retrospective analysis was performed using National Inpatient Sample data (2017 to 2019). Inclusion criteria included patients aged ≥18 years with primary diagnosis of CS using ICD10(R570). Multivariate regression analysis was used to assess MCS duration, mortality, length of stay (LOS), and costs.

Among 462,685 included patients, 38% were female, with a mean age of 66 years. Majority were White (67%), followed by Black (16.5%), and Hispanic (9%). IABP was utilized in 13% of cases, Impella in 6%, and ECMO in 0.9%. No significant difference was observed in MCS placement between weekdays vs weekends. However, weekend admissions showed higher mortality rates with an odd ratio (OR) of 1.06(p <0.00, CI 1.03-1.09), particularly among females OR 1.25(p<0.00, CI 1.22 – 1.289). Urban non-teaching hospitals exhibited highest mortality rate, followed by Urban teaching. ECMO was associated with highest mortality OR 2.08(p < 0.00, CI 1.93-2.82), followed by Impella OR of 1.47 (p < 0.00, CI 1.37 – 1.59), and IABP OR 0.723 (p < 0.00, 0.685-0.765). LOS was lowest in Impella group, followed by IABP, while ECMO showed non-significant LOS increase. Mean total charge varied among MCS groups with ECMO being highest.

The findings highlight several important aspects of CS management. Elevated mortality rates during weekend admissions suggest potential disparities in care access or delivery, necessitating investigation and interventions to ensure consistent quality of care throughout the week. Increased mortality among females, variations across different hospital settings, impact of MCS devices on LOS and costs emphasize the need for tailored approaches to enhance patient outcomes and resource utilization efficiency.
Abstract 4115846: Early Right and Left Ventricular Echocardiographic Parameters Improvement in Obese Patients After Bariatric Surgery.
Authors: Polewczyk Anna , Siudak Zbigniew , Cecha Patrycja , Bryk Piotr , Nawacki Lukasz , Bociek Agnieszka
Published: November 2024

Background:
Severe obesity causes hemodynamic changes in the circulatory system, which leads to the development of heart failure with either preserved or reduced ejection fraction. Weight loss achieved through bariatric surgery is likely to possibly reverse many of hemodynamic and structural abnormalities caused by obesity.

Hypothesis:
Right and left ventricular parameters of heart failure and function improve as soon as 3 months after surgery.

Methods:
Detailed echocardiographic parameters assessing left and right ventricular function in severely obese patients undergoing bariatric surgery were analyzed. The following parameters of left and right ventricular function were compared in the examinations performed before, 3 and 6 months after surgery: left ventricular ejection fraction (LVEF), LV and RV global longitudinal strain (GLS), peak early (e’) and late (a’) diastolic annular velocities (lateral and septal) with calculation of E/e’ ratios, left atrium volume index ( LAVI), TRV (tricuspid regurgitation velocity), tricuspid annular plane systolic excursion (TAPSE), maximum systolic velocity of the lateral part of the tricuspid annulus-s’ and accelerated pulmonary time (AcT).

Results:
Forty obese patients (76% women) with mean BMI 40.3 (SD 5.6) and mean age of 42.4 (SD 11.9) years were enrolled. BMI as 6 months was 31.2 (SD 5.1). Baseline and follow-up results of echocardiography are presented for both left and right ventricular parameters in Table 1 and Table 2.

Conclusions:
Only GLS for right and left ventricle, FWS and TRV improve siginicantly within 6 months from bariatric surgery. On the other hand, these changes are significant as early as 3 months after bariatric surgery.
Abstract 4116177: Metabolic and Pharmacokinetic Profiling of Ketone Ester by Background SGLT2 Inhibitor Therapy in Heart Failure with Reduced Ejection: A Phase I Clinical Trial
Authors: Selvaraj Senthil , He Caroline , Thompson Elizabeth , Hornik Christoph , Devore Adam , Patel Chetan , Mentz Robert , Fudim Marat , Kwee Lydia , Taylor Lacey , Milosovic Stephanie , Hurdle Melissa , Cade William , Ilkayeva Olga , Muehlbauer Michael , Newgard Christopher , Kelly Daniel , Zamani Payman , Margulies Kenneth , Shah Svati
Published: November 2024

Background:
Growing evidence supports a therapeutic role for ketones in HFrEF. However, no pharmacokinetic (PK) studies are available to guide further investigation, and uncertainty exists regarding use with the ketogenic SGLT2i and dose-dependent effects.

Methods:
We conducted a phase I trial of two doses of ketone ester (KE, 250 mg/kg and 500 mg/kg) in 20 HFrEF participants, stratified by SGLT2i use. Non-compartmental analysis assessed PK parameters of ketones. Paired t-tests and generalized linear mixed models assessed changes in mass-spectrometry based targeted metabolites, blood gas, and vital sign assessments up to 4 hours after dosing.

Results:
The mean age was 66.0±14.8 years, 45% were women, 30% were non-White, and average EF was 33±13%. The median (25
th
–75
th
percentile) T
max
, C
max
, and T
1/2
for total ketones with 250 and 500 mg/kg doses were 1.01 (0.64-1.24) and 1.58 (1.06-1.99) hours, 2317 (2165-2491) and 3354 (3291-3538) µM, and 0.85 (0.66-1.24) and 2.04 (1.36-3.47) hours, respectively (
Figure 1A
). One hour after KE consumption, insulin levels robustly increased, while non-esterified fatty acids, branched-chain amino acids, and acylcarnitines decreased except for C2/C4-OH acylcarnitines, which increased (FDR-adjusted p-value<0.05). Increases in ketones and C2/C4-OH acylcarnitines were dose-dependent, while background SGLT2i was associated with blunting of the decrease across acylcarnitines. One hour post KE, heart rate initially rose by 4 (95%CI 2-6) beats/min, while systolic blood pressure (-7, 95%CI -12, -2 mmHg), pH (-0.07, 95%CI -0.08, 0.05), and bicarbonate (-3, 95%CI -4, -2 mEq/L) decreased, with dose-dependent acid-based effects (
Figures 1B-C
). These values returned close to baseline by 4 hours. Adverse events were infrequent and mild.

Conclusions:
Acute KE ingestion is associated with rapid changes in several key metabolic pathways, with differential effects imparted by background SGLT2i (fatty acid metabolism) and dose (ketone metabolism). Hemodynamic effects were transient and irrespective of dose/SGLT2i, while acidotic effects were heightened with increasing dose. These data support the safety of combined KE and SGLT2i in HFrEF and provide grounding data for further trials.