bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 4141063: Differences on Periprocedural Blood Flow Dynamics between Self- and Balloon-expandable Valves in Patients with Small Aortic Annulus Undergoing Transcatheter Aortic Replacement
Authors: Hamaya Takeshi , Nagai Toshiyuki , Kamiya Kiwamu , Tsuneta Satonori , Komoriyama Hirokazu , Takahashi Yuki , Takahashi Akinori , Mori Yuki , Naito Seiichiro , Takenaka Sakae , Ishizaka Suguru , Sato Takuma , Konishi Takao , Anzai Toshihisa
Published: November 2024

Backgrounds:
A recent trial has shown that the supra-annular self-expanding valve (SEV) is superior for valve function and noninferior for clinical outcomes at one year compared to the balloon-expandable valve (BEV) in patients with aortic stenosis (AS) and small aortic annulus (SAA) undergoing transcatheter aortic valve replacement (TAVR). However, differences on blood flow hemodynamics between the valves remain unclear. We aimed to investigate these differences between the SEV and BEV using four-dimensional flow cardiovascular magnetic resonance imaging (4D flow CMR).

Methods:
We prospectively examined 95 consecutive patients with severe AS and a SAA who underwent TAVR between May 2018 and April 2024 (31 SEV and 64 BEV). SAA was defined as ≤430 mm
2
based on the trial. We compared the changes in blood flow patterns, wall shear stress (WSS), and energy loss (EL) in the ascending aorta (AAo) between the SEV and BEV using 4D flow CMR.

Results:
The absolute reductions in the vortical flow, helical flow and flow eccentricity were significantly higher in the SEV group than in the BEV group after TAVR (SEV: -0.35 ± 0.88 vs. BEV: 0.15 ± 1.01,
P
= 0.02, SEV: -0.87 ± 0.81 vs. BEV: -0.38 ± 0.88,
P
= 0.003, and SEV: -0.61 ± 0.92 vs. BEV: -0.21 ± 0.83,
P
= 0.037, respectively) (Figure 1A-C). The absolute reduction of average WSS was significantly higher in the SEV group than that in the BEV group after TAVR (SEV: -1.9 [-3.7 – -0.90] Pa vs. BEV: -0.94 [-2.6 – 0.35] Pa,
P
= 0.049) (Figure 1D). The systolic EL significantly decreased after TAVR in both groups, whereas its absolute reduction was comparable between the groups (SEV: -4.9 [-7.6 – 0.21] mW vs. BEV: -4.4 [-9.5 – 1.5] mW,
P
= 0.61).

Conclusions:
The vortical flow, helical flow, flow eccentricity, and average WSS in the AAo after TAVR were significantly decreased in the SEV compared to those in the BEV in patients with SAA undergoing TAVR. Our findings suggest the favorable profile on blood flow dynamics in the supra-annular SEV, possibly supporting its superiority of valve function.
Abstract 4141090: Implications of Tricuspid Regurgitation Severity in Patients Undergoing Mitral Transcatheter Edge-to-Edge Repair
Authors: Shechter Alon , TAHERI HOMA , NAGASAKA TAKASHI , Gupta Aakriti , Kaewkes Danon , Patel Vivek , Suruga Kazuki , Dhillon Manvir , Koseki Keita , Koren Ofir , Makar Moody , Skaf Sabah , Patel Dhairya , Chakravarty Tarun , Makkar Raj , Siegel Robert
Published: November 2024

Background–
Prognostically-meaningful tricuspid regurgitation (TR) surrounding transcatheter edge-to-edge repair (TEER) for mitral regurgitation (MR) is ill-defined.

Objective–
To explore the prevalence, correlates, and consequences of TR grades and postprocedural trends among mitral TEER patients.

Methods–
This is a single-center, retrospective analysis of isolated, first-time interventions. Pre-, intra-, and post-procedural aspects up to 1-year, of them the primary composite outcome of all-cause deaths or heart failure (HF) hospitalizations, were assessed according to continuous/categorical TR severity at baseline and 1-month post-TEER.

Results–
Overall, 1,287 individuals (60.3% males, age 78 (IQR, 69-85) years, 52.9% with functional MR) were included. Below-moderate, moderate, and above-moderate TR affected 48.4%, 29.5%, and 22.1% of patients, respectively. Increasing TR severity was accompanied by higher rates of functional, severe MR, greater comorbidity, and more advanced HF. Although not affecting technical and echocardiographic procedural success, moderate-and-above TR degrees were associated with higher incidence of mortality, HF admissions, and functional class III-IV post-procedure, with moderate-to-severe and greater TR independently conferring increased risks for the various outcomes (primary endpoint – HR 1.36, 95% CI 1.21-1.80, p=0.027). One-month postprocedural TR severity directly correlated with and was generally similar to or worse than its baseline counterpart. Rather than the direction/magnitude of change between the two, moderate-and-above grade at 1-month, observed in 37.1% of eligible patients, emerged as predictive of the primary outcome’s risk.

Conclusion–
Among mitral TEER patients, above-moderate TR at baseline and the closely-related moderate-and-above TR at 1-month post-procedure are highly prevalent and signal suboptimal outcomes. The potential benefit of simultaneously addressing such significant TR at the time of mitral TEER warrants further investigation.
Abstract 4141129: Temporal Trends in Substance Use and Ischemic-Heart disease related mortality in the United States: Cross-sectional Analysis of a National Database from 1999 to 2020
Authors: Farhan Syed Husain , Qazi Shurjeel , Ali Syeda Ayesha , Khan Adam , Ansari Huzaifa , Murtaza Mustafa , Zuberi Zaid , Ishtiaq Jawad , Noman Ayesha , Memon Abdul Basit Jawed , Siddiqi Rabbia
Published: November 2024

Background:
There is a scarcity of data regarding trends in substance use (SU) and mortality related to ischemic heart disease (IHD) in the United States (US).This study aims to evaluate deaths linked to SU+IHD in the US by utilizing the CDC Wide-ranging Online Data for Epidemiologic Research database (CDC WONDER).

Methods:
The CDC WONDER database was used to access the mortality data of adults aged ≥25 from 1999 to 2020. Both substance use and IHD were mentioned as contributing or underlying causes of death. Results, presented as age-adjusted mortality rates (AAMR) per 100,000 population, underwent Joinpoint regression for trend analysis and annual percentage change (APC).

Results:
Between 1999 and 2020, a total of 236,832 deaths were attributed to IHD among patients with substance use (AAMR = 4.9, 95% CI: 4.91-4.95). The overall AAMR depicted a consistent rising trend from 3.29 in 1999 to 7.91 in 2020.Throughout the study period, males consistently exhibited higher overall AAMRs compared to females (Male: 8.3 vs Female: 1.9). Among racial/ethnic groups, non-Hispanic American Indian [NH-AI] individuals had the highest AAMRs (10.9, 95% CI: 10.6-11.3), followed by non-Hispanic blacks [NHB] (6.5, 95% CI: 6.5-6.6), non-Hispanic Whites [NHW] (5.0, 95% CI: 5.0-5.1), and Hispanics (3.5, 95% CI: 3.4-3.5). Notably, non-Hispanic Asian/Pacific Islander [NH-API] individuals had the lowest AAMR (1.2, 95% CI: 1.1-1.2). Regionally, the West reported the highest mortality rates (6.3, 95% CI: 6.3-6.4), followed by the Midwest (4.8, 95% CI: 4.8-4.9) and the South (4.6, 95% CI: 4.6-4.7), while the Northeast reported the lowest mortality rate (3.9, 95% CI: 3.9-4.0). Moreover, when comparing urbanization status, metropolitan areas had a higher AAMR value compared to metropolitan areas in 1999, however this trend sharply reversed to non-metropolitan areas having a higher AAMR in 2020 (1999 non-metro: 3.1 vs. metro: 3.3; 2020 non-metro: 9.2 vs. metro: 7.6).

Conclusion:
Our findings underscore a troubling rise in IHD related mortality among substance users in the US. Addressing gender, racial/ethnic, and regional disparities is crucial for targeted interventions to reduce mortality rates and improve cardiovascular health outcomes.
Abstract 4141131: Pathophysiological evidence for abnormal P-wave terminal force reflects atrial myopathy
Authors: Kim Juntae , Kim Daehoon , Kwon Oh-Seok , Yu Hee Tae , Kim Tae-Hoon , Uhm Jae-Sun , JOUNG BOYOUNG , Lee Moon-Hyoung , Pak Hui-Nam
Published: November 2024

Background:
Although P-wave terminal force (PWTF), a marker of atrial myopathy, has been implicated in predicting incident atrial fibrillation (AF) and ischemic stroke, its pathophysiological mechanisms remain unclear. This study investigates the association between abnormal PWTF and atrial myopathy, diastolic function, epicardial adipose tissue (EAT), or AF recurrence following AF catheter ablation (AFCA).

Methods:
We included 3,528 AF patients (59.7 (10.8) years, 28.8% female, 64.2% paroxysmal AF) who underwent AFCA with baseline and 1-year follow-up echocardiograms. We evaluated the characteristics of the patients with abnormal PWTF (≥4000 μV × ms) and its association with clinical, hemodynamical, and imaging parameters.

Result:
Patients with AF and abnormal PWTF (≥4000 μV × ms) were older (p=0.001) and had higher proportions of male (p<0.001) and non-paroxysmal AF (p<0.001), higher CHA
2
DS
2
-VASc (p=0.011), H
2
FPEF scores (p=0.003), higher left atrial (LA) dimension (p<0.001), left ventricular mass index (p=0.001), LA pressure (n=3,067, p=0.014), and atrial EAT volume (p<0.001), and lower LA strain (n=368, p=0.036) than their counterpart. The patients with abnormal PWTF were independently associated with age (OR 1.01 [1.00-1.02], p=0.007), male gender (OR 1.64 [1.33-2.01], p<0.001), non-paroxysmal AF (OR 1.37 [1.14-1.66], p=0.001), LA volume index (OR 1.02 [1.01-1.03], p<0.001), or atrial EAT volume (OR 1.00 [1.00-1.01], p=0.028). Among 2,929 patients who did not recur within a year, PWTF was an independent predictor of blunted LA reverse remodeling a year after AFCA (OR 0.97 [0.94-0.99], p=0.029). During a median follow-up of 31 (interquartile range 15–61) month, patients with abnormal PWTF demonstrated a significantly higher AF recurrence (log-rank p=0.010; HR 1.14 [1.04-1.25], p=0.008).

Conclusion:
Abnormal PWTF is associated with a blunted LA reverse remodeling, atrial EAT volume, and an increased risk of AF recurrence following catheter ablation and is indicative of LA myopathy.
Abstract 4141191: Early-life Exercise Extends Healthspan and Attenuates Cardiovascular Aging in Aged Mice
Authors: Feng Mengya , Li Min , Lou Jing , Wu Guiling , Tan Yanzhen , Liu Xuyun , Liu Jiankang , Zhang Xing , Gao Feng
Published: November 2024

Introduction:
Regular physical exercise is widely recognized for its beneficial effects on overall health. Despite emerging evidence that early-life experiences profoundly impact adult and aged health, the long-term effects of early-life exercise remain uncertain.

Hypothesis:
We hypothesized that early-life exercise extends healthspan and attenuates cardiovascular aging in aged mice.

Methods:
Male and female C57BL/6J mice were subjected to a 3-month swimming exercise regimen starting from 1 month of age (1.5 hour per day, 5 days per week), while no exercise intervention was conducted at other times. The sedentary group was raised under similar conditions. The healthspan of aged male and female mice was assessed, including overall metabolic function, cardiovascular function, frailty index and other relevant measurements. Transcriptional profiling of young and old mice was performed to gain insights into the mechanisms underlying the effects of early-life exercise on aging.

Results:
Early-life exercise improved metabolic health in aged mice. Assessment of body composition showed increased lean mass in the exercise group. When subjected to food deprivation stress in metabolic chambers, aged mice with early-life exercise exhibited increased energy expenditure, carbohydrate oxidation, and fat oxidation levels in both males and females. Evaluation of frailty index at 24 months of age, involving 31 frailty phenotypes, indicated lower frailty index score in the early-life exercise group, suggesting an attenuation of age-related phenotypes. While no significant differences were observed in blood pressure and cardiac systolic function, early-life exercise was associated with improved cardiac diastolic function at 19 months of age. Furthermore, early-life exercise resulted in decreased heart-carotid pulse wave velocity and improved endothelial-dependent vascular relaxation in aged mice, indicating better vascular function in elderly mice with early-life exercise.

Conclusions:
The findings demonstrate that early-life exercise contributes to an increased healthspan, as evidenced by enhanced metabolic health and reduced frailty. Both male and female aged mice exposed to early-life exercise exhibit improved cardiovascular function.
Abstract 4141227: Characterization of NIMA-related kinase 7 (NEK7)-NLRP3 inflammasome complex in macrophages by combining CRISPR/Cas9 gene-editing with comprehensive proteomic
Authors: Nakamura Yuto , Chelvanambi Sarvesh , Kasai Taku , Whelan Mary , Sasaki Yusuke , Singh Sasha , Aikawa Elena , Aikawa Masanori
Published: November 2024

Background:
The aberrant activation of the NLRP3 inflammasome in macrophages promotes chronic inflammation in cardiovascular disease (CVD). NEK7 is essential to the NLRP3 inflammasome’s function, however, its role in inflammasome-mediated macrophage activation has yet to be elucidated.

Methods&Results:
We employed CRISPR/Cas9 gene editing to delete NEK7 in human primary macrophage cells (PBMCs) and in a macrophage-like cell line (THP-1). First, we employed mass spectrometry-based proteomics to monitor the response of Scramble control (ΔScr) or NEK7-null (ΔNEK7)-THP-1 cells to monosodium urate crystal (MSU). We quantified 4,030 proteins representing ΔNEK7-THP-1 and ΔScr-THP-1 conditions, analyzed at 4 timepoints (0hr, 1hr, 3hr, 6hr; MSU treamtent). NEK7 was identified in ΔScr but not in ΔNEK7 cells. In order to identify proteins whose abundances were suppressed by ΔNEK7, we performed a multiplexed high-dimensional clustering and network analysis using our custom made software (
XINA
, Fig.A). Specifically, we identified NOD-like receptor and Interleukin-1 (IL-1) signaling in clusters 16 and 17, that a) increased steadily over the timepoints and b) were overrepresented by proteins from the ΔScr condition (Fig.A, red rectangles). Whereas in ΔNEK7, these proteins migrated to either clusters 3, 5, 25, or 35 (Fig.B, alluvial plot), indicating their suppression (Fig.A, blue rectangles). In ΔNEK7-PBMCs, IL-1β secretion decreased in response to MSU compared to ΔScr-PBMCs (Fig.C, n=8); and less chemotaxis as determined by high-content imaging that monitored PBMC migration (Fig.D, n=6). Finally, we confirmed that small molecule inhibitor of the NLRP3-NEK7 complex itself decreased IL-1β secretion in an MSU-elicited peritonitis mouse model (C57BL/6J, n= 8, Control: PBS, p<0.05).

Conclusions:
NEK7 itself is sufficient as a therapeutic target to suppress inflammasome-mediated macrophage activation; providing molecular bases for the development of new therapies for CVD.
Abstract 4141241: Pulmonary dynamic hyperinflation augments pulmonary capillary wedge pressure during exercise in patients with heart failure with preserved ejection fraction
Authors: Leahy Michael , MacNamara James , Brazile Tiffany , Wakeham Denis , Samels Mitchel , Hearon Christopher , Tomlinson Andrew , Balmain Bryce , Babb Tony , Levine Benjamin , Sarma Satyam
Published: November 2024

Introduction:
Adults with heart failure with preserved ejection fraction (HFpEF) have an exaggerated rise in pulmonary capillary wedge pressure (PCWP) with exercise. Pulmonary function in patients with HFpEF is often flow limited, thereby perpetuating dynamic hyperinflation (DH) and breathing at a mechanically unfavorable percentage of total lung volume. We therefore sought to characterize the impact of DH on PCWP in adults with HFpEF during exercise.

Methods:
Twenty-seven patients with HFpEF were evaluated (Age: 70 ± 7 years, Female: 70 %, BMI: 38.1±6.3 kg/m
2
). PCWP and central venous pressure (CVP, right heart catheterization), oxygen uptake (breath by breath), cardiac output (direct Fick), and ventilation were measured upright at rest, 20 W, and peak exercise (73 ± 27 W) on a semi-recumbent cycle ergometer. End-expiratory lung volume was determined by having patients complete inspiratory capacity maneuvers during rest and exercise. DH was defined as an increase in end-expiratory lung volume of >150ml from rest.

Results:
End-expiratory PCWP was greater in patients with DH at 20 W (DH: 24 ± 6 mmHg vs. Normal: 18 ± 6, p=0.033) and peak exercise (DH: 44 ± 9 vs. Normal: 31 ± 6 mmHg, Panel A, p=0.002). The effect of DH occurred despite similar change in stroke volume (DH: 29 ± 15 vs. Normal: 37 ± 11 mL, p=0.164) and cardiac output (DH: 10.4 ± 1.7 vs. Normal: 11.1 ± 2.7 L/min, p=0.420) at peak exercise; however, BMI was greater in patients with DH (40.1 ± 6.0 vs. 34.4 ± 5.4 kg/m
2
, p=0.020). The degree of dynamic inflation was significantly associated with end-expiratory PCWP during exercise (slope= 0.531, R
2
= 0.281, p= 0.005, Panel B).

Conclusion:
Patients with HFpEF who dynamically hyperinflate during exercise have greater PCWP than those who do not. DH was associated with obesity and the severity of hyperinflation scaled proportionally to higher exercise PCWP. These findings indicate the augmented exercise PCWP in patients with HFpEF may not be entirely attributed to ventricular stiffness, but also a consequence of increased intrathoracic pressure from dysfunctional ventilatory mechanics.
Abstract 4141274: Impact of Oxidative Stress on Aortic Vulnerable Plaques Detected by Non-obstructive General Angioscopy
Authors: Kojima Keisuke , Tanaka Yudai , Mizobuchi Saki , MIGITA SHOHEI , Fukumoto Katsunori , Ebuchi Yasunari , Arai Riku , Murata Nobuhiro , Fukamachi Daisuke , Okumura Yasuo
Published: November 2024

Background:
Atherosclerosis is the most common cause of cardiovascular death. Oxidative stress is related to the initiation and progression of atherosclerosis. However, how oxidative stress affects the progression of atherosclerosis in vivo has not yet been fully investigated. Non-obstructive general angioscopy (NOGA) can meticulously visualize directly aortic atherosclerosis in vivo. The purpose of this study was to evaluate the relationships between oxidative stress and NOGA-derived aortic plaques.

Methods:
We investigated 120 consecutive cases with coronary artery disease evaluated for the aorta by NOGA between July 2021 and February 2024. Atherosclerotic lesions of the aorta were screened using NOGA immediately after coronary arteriography. NOGA examination evaluated the counts of ruptured plaques, chandelier signs, intense yellow plaques, and red thrombi in the aorta. Regarding the number of each plaque, we assessed the proportion of aortic findings detected by NOGA at each vertebral level. Derivatives of reactive oxygen metabolites (d-ROMs) levels as indices of reactive oxygen species production were evaluated.

Results:
The mean age was 66 years, and the median d-ROM value was 289 U.CARR [interquartile range: 251-339]. The d-ROM value was significantly correlated with the proportion of ruptured plaques (r=0.28, p=0.015), but not correlated with the other plaque characteristics. In a multiple linear regression analysis for the proportion of ruptured plaques in the aorta, d-ROMs were one of the independent factors adjusted for age, sex, hypertension, dyslipidemia, and diabetes mellitus (β=0.14, p=0.004).

Conclusion:
The value of d-ROMs was related to the proportion of ruptured plaques in the aorta, but not to the proportion of the other plaque characteristics. Oxidative stress may help to elucidate the mechanism for the progression of aortic atherosclerosis.
Abstract 4141276: Valvular oxidized phospholipids correlate with severity of human aortic valvular stenosis
Authors: Resch Craig , Stamenkovic Aleksandra , Surendran Arun , Shah Ashish , Ravandi Amir
Published: November 2024

Introduction:
Aortic valve stenosis (AVS) is a degenerative disease characterized by progressive calcification and stenosis, driven by a multifactorial inflammatory process. Oxidized phospholipids (OxPL) have been implicated in this process, yet their presence in aortic valve tissue remains unexplored. This study aims to fill this gap by developing a sensitive method to identify and quantify OxPL in the plasma and tissue of patients with severe AVS.

Methods:
We obtained aortic valve tissue from 70 patients undergoing aortic valve replacement surgery. The tissue samples were subjected to derivatization with DNPH, followed by LC/MS/MS analysis, enabling the identification and quantification of 60 individual OxPL across five different phospholipid classes.

Results:
Our analysis identified 34 OxPL species across five phospholipid classes in human valvular tissue, including oxidized phosphatidylcholine (OxPC), phosphatidylethanolamine (OxPE), phosphatidylinositol (OxPI), and phosphatidylserine (OxPS). OxPC was the most abundant class, with PONPC being the most prevalent molecule, constituting 35% of total OxPL. We observed a significant increase (p<0.05) in 20 OxPL species in valvular tissue when comparing mild to moderate to severe valve stenosis based on pressure gradient. The most significant change occurred between mild and moderate AVS as PONPC increased by 90% (p=0.012) and total OxPC increased by 83% (p=0.004). Compared to plasma, valvular tissue had more OxPS species present and an increase in longer chain fatty acid aldehydes in the SN-2 position of OxPCs.

Conclusion:
Our findings indicate that OxPL infiltration of the valve tissue is an early event in the progression of AVS. This suggests that early intervention with OxPL-lowering therapies may prove beneficial in managing AVS.
Abstract 4141287: Sodium Glucose Cotransporter-2 Inhibitors (SGLT2i) and Improves Function in ANOCA Patients
Authors: Tipler Paxson , Tapp Danielle , Schmidt Christian , Ashokprabhu Namrita , Kaur Sukhleen , Haygood Denaja , Hamstra Michelle , Owens A. Phillip , Henry Timothy , Quesada Odayme
Published: November 2024

Introduction:
Angina with non-obstructive coronary arteries (ANOCA) affects four million individuals in the U.S. and is associated with an economic burden that exceeds obstructive coronary artery disease (CAD). Sodium Glucose Cotransporter-2 Inhibitors (SGLT2i) are a novel class of glucose control medications initially indicated for use in type 2 diabetes that also reduce the risk major adverse cardiovascular events (MACE) in cardiovascular diseases. SGLT2i have recently been found to reduce the risk of MACE in patients with heart failure with preserved ejection fraction (HFpEF), which shares a common pathophysiological mechanism (coronary microvascular dysfunction) to ANOCA. Here, we examined the effects of SGLT2i on symptoms in ANOCA patients.

Methods:
Utilizing the Women’s Heart Center (WHC) Registry, we conducted a retrospective chart review of ANOCA patients who previously underwent coronary functional testing (CFT), were prescribed SGL2i, and were assessed for follow-up within 6 months. All brands of SGLT2i (dapagliflozin and empagliflozin) were included and symptoms were assessed utilizing validated questionnaires (NYHA HF and CCS angina class) pre- and post-treatment.

Results:
Among 34 ANOCA patients who underwent CFT and were clinically treated with SGLT2i’s, 29 (88%) were female (mean age=60.2; SD=11.4) and median treatment duration was 276 days (IQR:151,531). At the time of CFT, 50% had diabetes, 68% had hypertension, 97% had dyslipidemia, and 26% had a history of obstructive CAD. Among ANOCA patients, there were significantly fewer patients reporting angina at CCS class of 3 or 4 (moderate or severe limitation) post SGLT2i treatment (McNemar’s Exact, p=0.039, Figure 1). Among ANOCA patients with contaminant HFpEF (N=15, 53%), there were significantly fewer patients reporting a functional impairment at NYHA class of III and IV (marked or severe limitation) post SGLT2i treatment (McNemar’s Exact, p=0.016).

Conclusions:
SGLT2i show potential for reducing angina in ANOCA patients and improving function in patients with both ANOCA and HFpEF. Together, these data suggest benefit of SGLT2i in ANOCA patients and future studies should examine the effect these drugs have on underlying mechanisms (CMD).
Abstract 4141294: Cerebral Oxygen Saturation for Early Prognostication Following Veno-Arterial Extracorporeal Membrane Oxygenation
Authors: Li Yi , Geng Cong , Chen Nan , Chen Hui , Huang Jian , Lu Shiqi , Zhang Ke
Published: November 2024

Introduction:
Veno-arterial extra-corporeal membrane oxygenation therapy (VA-ECMO) following refractory cardiogenic shock (r-CS) or cardiac arrest (r-CA) is associated with morbidity and mortality. Early prediction of neurologic outcomes is crucial , but data remains limited in the clinical setting.We investigated the prognostic value of regional oxygen saturation (rSO
2
), using near infrared spectroscopy (NIRS) for the quantitative measurement of cerebral oxygenation.

Methods:
This was an observational cohort study of patients underwent VA-ECMO with routine cerebral rSO
2
monitoring at the early phase following ECMO insertion in the intensive care unit from January 2020 and January 2024.Using NIRS sensors,continuous rSO
2
monitoring was assessed during the first 72 hours. Trends of rSO
2
over time were correlated to 28-day mortality, and the prognostic performance of the rSO
2
, alone and in combination with the SAVE score, was evaluated.

Results:
A total 87 consecutive patients were studied (59 r-CS/28 r-CA).The SAVE score was -8.67 ± 4.56. The 28-day survival rate was 40.2% (35/87 patients). Non-survivors (n=52) had significantly lower rSO
2
than survivors at all time-points (all
p
<0.001). Abnormal rSO
2
(<50%, at any time from 24 to 72 hours) was 100% specific for 28-day mortality, with 0% false positives. Adding SAVE score to the rSO
2
provided the best prognostic performance (specificity 100% [95% confidence interval 90-100%], sensitivity 77% [62-89%], area under the ROC curve 0.91).

Conclusions:
Quantitative rSO
2
alone had excellent ability to predict a poor outcome from day 1 after VA-ECMO insertion, with no false positives. Combining rSO
2
and SAVE score increased sensitivity of outcome prediction, while maintaining 100% specificity.
Abstract 4141312: Safe Initial Dosing of Innovative Enalapril Orodispersible Minitablets in Newly Treated Newborns, Infants and Young Children with Heart Failure – Results of a Population Pharmacokinetic Analysis of the LENA Trials
Authors: Steichert Melina , Laeer Stephanie , Cawello Willi
Published: November 2024

Background:
Safe dosing in children with heart failure requires consideration of clinically relevant covariates. In the European project Labeling of Enalapril from Neonates up to Adolescents (LENA), heart failure was treated with innovative enalapril orodispersible minitablets (ODMT) using an age- and weight-dependent dosing regimen.

Research Question: Does the population pharmacokinetic analysis of the LENA data reveal relevant clinical covariates in dosing besides age and weight for newborns, infants and young children newly treated with enalapril ODMT?

Methods:
We analyzed data of ACE inhibitor naïve subjects with heart failure due to congenital heart disease (n=31) or dilated cardiomyopathy (n=3) from the prospective, open-label, multicenter phase II/III pharmacokinetic bridging studies using NONMEM
®
. Allometric scaling was applied to the clearance (CL/F) and volume of distribution (V
d
/F) of enalapril and enalaprilat. The covariates age, sex, serum creatinine and Ross score were tested using stepwise covariate modeling. Simulations were conducted to assess the effects of the identified covariates.

Results:
In total, 173 enalapril and 268 enalaprilat serum concentrations from 34 subjects (25 days–2.1 years, median age=0.3 years) were included in the analysis. A combined model with a one compartment model of enalapril coupled with a one compartment model of enalaprilat with absorption lag was chosen as the structural model. The population estimates were 4.98 L (V
d
/F of enalapril), 34.1 L (V
d
/F of enalaprilat), 4.61 L/h (CL/F of enalapril) and 1.55 L/h (CL/F of enalaprilat). For enalaprilat, part of the variance in CL/F could be explained by age and serum creatinine, while part of the variance in V
d
/F could be explained by the Ross score. The simulations indicated that age, weight, and serum creatinine values above the normal reference range are clinically relevant covariates for the initial dose and the dose at steady state, while the Ross score is a relevant covariate for the initial dose. An increase in the Ross score by one point leads to an average increase in the initial maximum concentration of enalaprilat of 24% in the examined Ross score range from 0 to 11.

Conclusion:
The newly detected covariate Ross score provides the scientific basis for considering the severity of heart failure at the initial dose. The initial dose should be lowered depending on the level of the Ross score to avoid high peak concentrations and a potential drop in blood pressure.
Abstract 4141319: Enhancing Prognostic Prediction in STEMI Patients: The Incremental Value of Computational Pressure-Fluid Dynamics Applied to Index of Microcirculatory Resistance
Authors: Duan Yang , Zhang Junyi , Zhou Yafeng
Published: November 2024

Background:
The computational pressure-fluid dynamics applied to index of microcirculatory resistance, derived from coronary angiography (CPFD-caIMR) is a promising alternative method of IMR to evaluate the prognosis of STEMI patients. This study aim to evaluate the incremental value CPFD-caIMR and MVO in predicting MACE after patients with undergoing primary percutaneous coronary PPCI.

Methods:
A total of 292 patients who met the inclusion criteria were selected retrospectively from 1107 STEMI patients from January 2019 to January 2021 in Affiliated Hospital of Xuzhou Medical University in China. All patients with STEMI underwent CPFD-caIMR and MVO assessment. The patients were categorized into four groups based on CPFD-caIMR and MVO presence: 1) CPFD-caIMR ≤40U without MVO; 2) CPFD-caIMR >40U without MVO; 3) CPFD-caIMR ≤40U with MVO; and 4) CPFD-caIMR >40U with MVO. The primary endpoint of the study was MACE, defined as cardiovascular or all-cause deaths, non-fatal MI, revascularization including target vessel reconstruction, heart failure readmission.

Results:
Within the included 292 patients, a notable proportion of 101 cases (34.6%) revealed discrepancies between CPFD-caIMR and MVO. Among these, 103 patients (35.3%) exhibited CPFD-caIMR values of ≤40 without MVO, while 88 patients (30.1%) displayed CPFD-caIMR values of >40 with MVO on CMR. Both MVO (HR: 2.750, p=0.033) and CPFD-IMR>40U (HR: 3.572, p=0.001]) were predictors of MACE over 12 months. Specifically, for every 1-unit increase in CPFD-IMR>40U, MACE increased by 3.572 units. Furthermore, ROC curve analysis demonstrated that CPFD-caIMR>40U (AUC, 0.724, p＜0.001) and MVO (AUC, 0.667, p=0.001) were effective in predicting MACE. Notably, combined CPFD-caIMR and MVO increased the area under the curve for MACE to 0.820, p<0.001). Over 12 month of follow-up, Group 4 (HR: 8.765, p <0.001) but not Group 3 (HR: 3.474, p=0.029), Group 2(HR:3.554, p=0.045) had worse clinical outcomes compared with those with no significant CMD in Group 1.

Conclusion:
CPFD-caIMR is a novel method for noninvasive detection of microvascular reperfusion failure, and CPFD-caIMR > 40U can predict the prognosis of STEMI patients.When combined with CMR, CPFD-caIMR > 40U can be used to further stratify the risk of STEMI and to identify high-risk patients who may require more aggressive treatment during follow-up.
Abstract 4141320: Heart Failure Quality of Care and Outcomes among Asian Ethnic Groups in the United States
Authors: Huang Xiaoning , Yancy Clyde , Fonarow Gregg , Khan Sadiya , Shah Nilay
Published: November 2024

Background:
Asian populations in the United States experience heterogenous burden of cardiovascular disease (CVD). Heart failure (HF) hospitalization quality of care or outcomes have not been reported in these populations.

Methods:
Participants were adults age ≥18 years in the AHA Get with the Guidelines Heart Failure registry (2015-2023) who had a primary admission diagnosis of HF, and identified as Asian Indian, Chinese, Filipino, Japanese, Korean, and Vietnamese, or non-Hispanic White (NHW). Odds of optimal medical therapy (receiving up to three medication classes for which they were eligible based on ejection fraction [EF] and absence of contraindication [1: ACE inhibitor, ARB, or ARNI; 2: beta blocker; 3: mineralocorticoid receptor antagonist]), length of stay >4 days, and in-hospital mortality were evaluated in each Asian subgroup vs. NHW, with sex-stratified multivariable logistic regression models, adjusted for age; EF; diabetes, hypertension, and smoking history; and insurance status.

Results:
Among Asian (n=3,112) and NHW (n=315,994) registry patients with HF and reduced EF<40%, adjusted odds of optimal medical therapy vs. NHW were lower in Japanese (adjusted odds ratio [aOR] 0.69, 95% confidence interval [CI] 0.50, 0.94) and Vietnamese (aOR 0.68, 95% CI 0.48, 0.98) male patients, and higher in Asian Indian patients (male aOR 2.06, 95% CI 1.68, 2.53; female aOR 1.84, 95% CI 1.28, 2.64) (Table). Among Asian (n=7,261) and NHW (n=790,237) registry patients with HF and any EF, likelihood of length of stay >4 days vs. NHW was lower in Vietnamese male (aOR 0.65, 95% CI 0.45, 0.93), and Asian Indian (aOR 0.63, 95% CI 0.42, 0.94), Chinese (aOR 0.58, 95% CI 0.38, 0.88), and Filipina (aOR 0.66, 95% CI 0.48, 0.91) female patients. In-hospital mortality occurred in 2-4% of Asian patients and 3% of NHW patients, with no statistically significant differences in in-hospital mortality rates in Asian compared with NHW patients.

Conclusions:
HF quality of care may vary among Asian subgroups in the US. Quality improvement programs must identify and address the factors that result in variations in HF care among US Asian patients.
Abstract 4141342: Impact of sodium-glucose cotransporter-2 inhibitor on postoperative atrial fibrillation and myocardial injury after coronary artery bypass grafting in patients with diabetes
Authors: Li Zhongchen , Zeng Juntong , Zhang Heng , Zheng Zhe
Published: November 2024

Background:
Recent studies showed that sodium-glucose cotransporter 2 inhibitors (SGLT2i) significantly reduce the risk of atrial fibrillation (AF) and the recurrence of AF after catheter ablation in diabetic patients. However, there is no evidence of a relationship between SGLT2i use and the incidence of postoperative atrial fibrillation (POAF), a common complication after coronary artery bypass grafting (CABG). Additionally, the protective mechanisms of SGLT2i on cardiomyocytes suggest a possible association with reduced postoperative myocardial injury.

Methods:
SGLT2i use was defined as taking SGLT2i at the time of admission and discontinuing it at least 3 days before surgery. Adult diabetic patients without a history of AF undergoing primary CABG (±valve surgery) between October 2023 and December 2024 were included from a large prospective cohort. Patients with acute coronary syndromes or emergency surgery were excluded. Patients in the SGLT2i group were matched by propensity score with the control group (no SGLT2i use) at a 1:3 ratio. Generalized estimating equations were utilized for repeated measures data. Primary outcomes were the incidence of POAF and the level of high-sensitivity troponin I (hs-cTnI) within 5 days post-surgery. Secondary outcomes included in-hospital death, stroke, perioperative myocardial infarction (MI), acute kidney injury stage 2/3, reoperation, ICU stay duration, postoperative NT-proBNP levels, and blood inflammatory biomarkers. Diabetic ketoacidosis (DKA) was also monitored.

Results:
The cohort included 10,106 subjects, with 1,407 (13.9%) in the SGLT2i group. A total of 1,001 patients in the SGLT2i group and 3,003 in the control group were analyzed, with well-matched baseline characteristics after propensity scoring. No DKA events were found in either group. After adjusting for multiple confounding factors, the incidence of POAF was significantly lower in the SGLT2i group (19.6% vs. 25.7%, odds ratio: 0.686, 95% confidence interval: 0.592 - 0.794, P < 0.001). In the SGLT2i group, hs-cTnI levels within 5 days postoperatively decreased by an average of 0.36 ng/ml (95% CI: -0.707 to -0.012, P = 0.013). No significant differences were observed in postoperative NT-proBNP, inflammatory biomarkers, or ICU stay. No differences in other perioperative clinical outcomes were observed.

Conclusion:
SGLT2 inhibitors can reduce the incidence of POAF and levels of hs-cTnI following CABG, without an increased risk of other perioperative adverse events
Abstract 4141384: Integrated Multi-Omics Myocardial Analysis Suggests Impaired Alternative Fuel Utilization in Heart Failure with Preserved Ejection Fraction
Authors: Keykhaei Mohammad , Koleini Navid , Meddeb Mariam , Tajdini Masih , Mulligan Abigail , Sharma Kavita , Kass David , Hahn Virginia
Published: November 2024

Introduction:
Recent transcriptomic and metabolomic studies have suggested heart failure with preserved ejection fraction (HFpEF) myocardium exhibits metabolic insufficiency. Here we integrated targeted gene expression and proteomics to identify which fuel use pathways are likely compromised in HFpEF.

Hypothesis:
We hypothesize HFpEF has depressed gene/protein/metabolite levels related to metabolism of fatty acids, branched chain amino acids, and anaplerosis.

Methods:
Myocardial septal biopsies from HFpEF patients and non-failing controls were studied by Western blot for key proteins in fuel metabolism and cross-related to metabolomics (38 HFpEF, 20 control) and bulk RNAseq (41 HFpEF, 24 control). Protein abundance between groups was tested using Welch’s t-test.

Results:
Protein levels of CPT1 and CPT2 enzymes needed for acylcarnitine formation and rate-limiting for fatty acid metabolism, were similar in HFpEF vs controls. Proteins related to fatty acid uptake (ACSL1, P=0.002) and oxidation (ACAD [ACADM, P=0.02; ACADVL, P=0.009], HADH [HADHA, P<0.0001; HADHB, P=0.0006]), and master regulators
PPARa
(P<0.0001) and
PGC1a
(P=0.01), were significantly lower in HFpEF vs controls. Key enzymes in ketone metabolism had lower protein expression in HFpEF (SLC16A1 [ketone transporter, P=0.0002], BDH1 [P=0.003], ACAT [P=0.002]). Both BCAT2 (P=0.002) and BCKDH (P=0.0006) were lower in HFpEF, suggesting impaired oxidation of branched-chain amino acid (BCAA) and branched-chain ketoacids, concordant with metabolomic data. Proteins in anaplerotic pathways that replenish TCA intermediates were also lower in HFpEF, [ME (converts malate to pyruvate, P<0.0001), GOT (converts aspartate to oxaloacetate, P=0.036), and GLUD1 (converts glutamate to α-ketoglutarate, P<0.0001). Protein expression of the PCC family and MUT, responsible for replenishment of succinyl CoA, did not differ between groups.

Conclusions:
Multi-omic analysis of metabolic pathways in HFpEF suggests significant metabolic insufficiency, with reduced expression of key proteins and their mRNAs involved with fatty acid, ketone, BCAA, and anaplerotic metabolism. This reveals the HFpEF heart as particularly energy challenged and suggests potential metabolic therapy targets.
Abstract 4141387: Clinical Study on The Blood Pressure Changes in Patients with VEGFR-TKI-induced Hypertension During Anti-tumor Treatment
Authors: Li Jiaxin , Yu Jing
Published: November 2024

Background and Objective:
To investigate the differences in Ambulatory Blood Pressure Monitoring (ABPM) parameters in patients affected by VEGFR-TKI and tumors, and to summarize the relationship between VEGFR-TKI, tumors, and blood pressure.

Methods:
43 patients who received VEGFR-TKI anti-tumor treatment and developed induced hypertension were selected for ABPM. Additionally, 94 cases of tumor-associated hypertension and 96 cases of primary hypertension were randomly selected for comparison. The ambulatory blood pressure-related parameters between the VEGFR-TKI-related hypertension group and the tumor-associated hypertension group, as well as between the tumor-associated hypertension group and the primary hypertension group, were analyzed.

Results:
Compared with the tumor-associated hypertension group, the VEGFR-TKI-related hypertension group showed higher 24-hour average diastolic blood pressure [(85.37±13.21) vs. (80.41±10.71) mmHg,
t
=2.332,
P
=0.021], daytime average diastolic blood pressure [(85.98±13.19) vs. (80.69±10.98) mmHg,
t
=2.452,
P
=0.015]. Multivariate linear regression analysis revealed that after adjusting for tumor type and BMI, the use of VEGFR-TKI remained independently associated with nighttime average diastolic blood pressure (
B
=5.921,
P
=0.021). Compared with the primary hypertension group, the tumor-associated hypertension group exhibited significantly reduced nighttime systolic blood pressure decline rate [(1.10±9.01) vs. (6.33±6.87),
t
=-4.508,
P
<0.001] and nighttime diastolic blood pressure decline rate [(2.13±10.09) vs. (6.38±7.42),
t
=-3.317,
P
<0.001]. Multivariate linear regression analysis showed that after adjusting for age, BMI, and hypertension history, the tumor remained independently associated with nighttime systolic blood pressure decline rate (
B
=-5.336,
P
<0.001).

Conclusion:
In comparison with the tumor-associated hypertension group, VEGFR-TKI anti-tumor treatment induced predominantly increased diastolic blood pressure during nighttime periods, and the use of VEGFR-TKI was identified as an independent risk factor for elevated nighttime average diastolic blood pressure. In contrast to the primary hypertension group, tumors primarily influenced the blood pressure decline rate in dynamic blood pressure parameters, and the tumor was identified as an independent risk factor for reduced nighttime systolic blood pressure decline rate.
Abstract 4141422: Prognostic Value of Spleen Stiffness Assessed by Magnetic Resonance Elastography in Patients with Heart Failure
Authors: Takahashi Akinori , Nagai Toshiyuki , Tada Atsushi , Kato Yoshiya , Tsuneta Satonori , Mori Yuki , Hamaya Takeshi , Naito Seiichiro , Takenaka Sakae , Konishi Takao , Sato Takuma , Kamiya Kiwamu , Anzai Toshihisa
Published: November 2024

Background:
The interaction between the heart and spleen plays a crucial role in the cardio-splenic axis in patients with heart failure (HF). Several studies reported that spleen stiffness (SS) measured by magnetic resonance elastography (MRE) (SS-MRE) was a useful determinant of hepatic fibrosis and portal / venous pressure in patients with chronic liver disease. However, it is unclear whether higher SS-MRE is associated with elevated central venous pressure and worse clinical outcomes in patients with HF.

Methods:
We prospectively examined 216 consecutive chronic HF patients (120 male, mean age 66 ± 14 years, left ventricular ejection fraction 47 ± 17%) between April 2018 and February 2023 after excluding those with organic liver and spleen diseases. All patients underwent 3.0 Tesla MRE within 4 days of right heart catheterization. Representative images of MRE are shown in
Figure 1A
. We also assessed liver stiffness (LS) measured by MRE (LS-MRE). The primary outcome was a composite of all-cause death and hospitalization for HF.

Results:
Median SS-MRE and LS-MRE were 6.50 (interquartile range [IQR] 5.65-7.27) kPa, and 2.55 (IQR 2.33-2.83) kPa, respectively, with moderate correlation between the two parameters (r = 0.25,
P
<0.001). There was a significant correlation between SS-MRE and right atrial pressure (r = 0.15,
P
= 0.032). During a median follow-up period of 2.86 (IQR 1.30-4.12) years, the primary outcome occurred in 50 patients (18 all-cause deaths and 32 hospitalizations for HF). Cox regressions showed that SS-MRE was independently associated with the risk of the primary outcome (HR 1.18, 95% CI 1.03-1.37) after adjustments for age, sex, and other significant prognostic covariates. When divided the patients into two groups according to a median LS-MRE value, SS-MRE was associated with the risk of adverse events in patients with lower LS-MRE but not in those with higher LS-MRE (
P
for interaction = 0.014) (
Figure 1B and C
).

Conclusion:
Elevated SS-MRE was independently associated with worse clinical outcomes, especially in patients with lower LS-MRE. These findings suggest that elevated SS-MRE would reflect central venous congestion even in low LS, and is useful for risk stratification in patients with HF.
Abstract 4141501: 9p21.3 variants drive coronary calcification by suppressing statherin expression
Authors: Soheili Fariborz , Almontashiri Naif , Heydarikhorneh Niloufar , Vilmundarson Ragnar , Chen Hsiao-huei , Stewart Alexandre
Published: November 2024

Background:
Genetic variants on chromosome 9 at p21.3 confer a heightened risk of atherosclerosis and coronary artery calcification. The 9p21.3 variants cause the selective expression of non-coding RNA transcripts (ANRIL) that regulate many genes through ALU element mediated silencing. However, to date, none of these regulated genes account for the effect of 9p21.3 variants on coronary calcification.

Methods and Results:
To identify genes differentially regulated by the 9p21.3 risk variants, primary human aortic smooth muscle cells (HAoSMCs) from 11 different donors genotyped for 9p21.3 risk variants (n=3-4/genotype) were analyzed for whole-genome expression using microarrays. We identified the mRNA for the hydroxyapatite-binding protein statherin as the most impacted by 9p21.3 genotypes—its mRNA was silenced in carriers homozygous for risk variants. Transfection of ANRIL with an expression plasmid bearing the ALU element from the first intron of the Statherin gene silenced statherin expression. HAoSMCs also express another hydroxyapatite binding protein called matrix GLA protein (MGP). Mice lack a native statherin gene, and if they lose the
Mgp
gene, they develop severe arterial calcification and die of aortic rupture. In contrast, humans with MGP deficiency (aka Keutel syndrome) rarely develop calcified arteries, suggesting that statherin might compensate for MGP loss. As has been reported for MGP, statherin was found to inhibit bone morphogenic protein 4 (BMP4)-dependent activation of a BMP-responsive luciferase reporter, suggesting functional redundancy of statherin and MGP to inhibit arterial calcification. Lentiviral vectors expressing human statherin blocked calcification of primary aortic smooth muscle cells from
Mgp
KO mice. Furthermore, expression of human statherin from a transgene conditionally recombined only in smooth muscle cells prevented arterial calcification in
Mgp
KO mice.

Conclusion:
The 9p21.3 risk variants expedite arterial calcification by suppressing statherin expression. Since microcalcifications hasten atherosclerosis, targeting this statherin-dependent mechanism could reduce atherosclerotic burden and benefit up to 75% of individuals of European and Asian ancestry that carry the 9p21.3 risk variants.