bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 4135466: Feasibility of Using Existing Infection Surveillance Methods for Percutaneous Coronary Intervention-related Infections
Authors: Hashimoto Makiyo , Takahashi Akihiko , Yokouchi Mitsuko , Ko Aiko
Published: November 2024

Background:
Percutaneous coronary intervention (PCI) is a treatment that requires attention in terms of infection control, as it necessitates aseptic procedures similar to surgical operations. However, surveillance practices for PCI-related infections are uncommon, and no standardized surveillance program has been established.

Purpose:
To assess the feasibility of using existing surveillance methods to detect PCI-related infectious diseases.

Method:
To identify PCI-related bloodstream infections of local access sites, four existing case definitions, namely, laboratory-confirmed bloodstream infections (LCBI), clinical sepsis (CSEP), local access site infection (LASI), and exit site infection (ESI), were retrospectively applied to 1,037 patients who underwent PCI between April 2018 and March 2021. Of these, 167 experienced fever, underwent blood culture testing, and/or received antibiotics within 6 days of PCI. To confirm consistent evaluation, two independent infection control experts evaluated each case record according to the four case definitions.

Results:
Twenty-three patients (2.2%) were diagnosed with PCI-related infections, including two patients according to LCBI, 21 according to CSEP, and none according to LASI and ESI. Thirteen patients (LCBI: 1, CSEP: 12) received circulatory assist devices such as intra-aortic balloon pumping. Of the remaining 11 patients, 10 underwent emergency PCI, and one underwent elective PCI (
P
=0.0001). The average length of hospital stay was 16.1 days for patients with PCI-related infections and 4.7 days for non-infected patients (
P
<0.05).

Conclusion:
The positive diagnosis of PCI-related infections was predominantly based on CSEP. Many of these positive patients underwent emergency PCI and/or received circulatory assist devices. The results of the present study warrant further investigations with larger patient cohorts.
Abstract 4135531: The Ubiquitin-Specific Protease 30 Inhibitor, MTX652, Attenuates Cardiac Dysfunction And Remodelling In a Murine Model Of Transverse Aortic Constriction
Authors: Dunmore Rebecca , Haines Zoe , Williams Rachel , Jones Louise , Okell Tracey , Almond Sarah , Knights Charlotte , Aceves Pau , Parton Laura , Nurbhai Suhail , Thompson Paul
Published: November 2024

Introduction:
Mitochondrial abnormalities are a characteristic of heart failure leading to energy deprivation and disease worsening. The mitochondrial deubiquitinating enzyme USP30, removes ubiquitin and represses PINK1/PARKIN-mediated mitophagy leading to accumulation of dysfunctional mitochondria. In this study we investigated the role of MTX652, a clinical stage USP30 inhibitor, in a mouse model of cardiac hypertrophy using transverse aortic constriction (TAC).

Hypothesis:
Inhibition of USP30 will promote mitophagy resulting in clearance of dysfunctional mitochondria and improved cellular health leading to cardioprotective effects.

Aims:
To determine if MTX652 can protect from TAC induced cardiac hypertrophy and remodelling.

Methods:
Male C57BL/6 mice, 8 weeks old, were subjected to sham surgeries or TAC using a 26G needle to induce cardiac pressure overload. MTX652 (1.5 or 5 mg/kg,
n
=12-13) or vehicle (
n
=11) was administered orally, twice daily, starting 2 days post-surgery. Captopril (30 mg/kg/d,
n
=13) was also included as a positive control. After 4 weeks, echocardiography assessed left ventricle (LV) function and morphology. Cell based assays assessed MTX652 target engagement and TOM20 ubiquitination
in vitro.

Results:
LV hypertrophy and wall thickening was observed in TAC animals. Treatment with MTX652 decreased systolic LV volume (1.5 mg/kg p<0.05 and 5 mg/kg p<0.01) and diameter (1.5 mg/kg p<0.01 and 5 mg/kg p<0.05,) demonstrating comparable effects to Captopril. A reduction in anterior wall thickness in diastole was also observed with MTX652 (5 mg/kg, p<0.01). Cardiac dysfunction was also evident in TAC animals with MTX652 showing improvements in both ejection fraction (1.5 mg/kg and 5 mg/kg, p<0.0001) and fractional shortening (1.5 mg/kg and 5 mg/kg, p<0.0001).

Cellular target engagement for MTX652 was confirmed in HeLa-YFP-Parkin cells with an EC
50
of 2.7 nM (
n
=2). Furthermore, the USP30 substrate TOM20 was ubiquitinated following MTX652 treatment
in vitro
(EC
50
=6.1 nM,
n
=4) providing evidence of mitophagy activation, a finding also confirmed in mouse heart tissue (MTX652, 5mg/kg).

Conclusions:
The USP30 inhibitor, MTX652 significantly protected mice from TAC induced cardiac hypertrophy and LV dysfunction. Furthermore, MTX652 potentiates ubiquitylation of TOM20 as a mechanism to promote mitophagy. These data suggest our clinical stage molecule could provide a novel therapeutic approach for the treatment of cardiac hypertrophy and heart failure.
Abstract 4135861: Lipoprotein(a) and Its Impact on Left Ventricular Remodeling Over a Decade: The Multi-Ethnic Study of Atherosclerosis
Authors: Abdollahi Ashkan , Chehab Omar , Scarpa Bruna , Whelton Seamus , Ambale-Venkatesh Bharath , Wu Colin , Post Wendy , Bluemke David , Tsai Michael , Tsimikas Sotirios , Lima Joao AC
Published: November 2024

Background:
Lipoprotein (a) (Lp[a]) is associated with an increased risk of cardiovascular disease and mortality, as well as heart failure and myocardial fibrosis. However, the link between Lp(a) and cardiac remodeling as a pathway to adverse cardiac outcomes remains unknown.

Objectives:
This study investigated the relationship between Lp(a) levels and longitudinal changes in the left ventricular (LV) remodeling over a decade among individuals without a previous history of cardiovascular disease.

Methods:
2,366 Multi-Ethnic Study of Atherosclerosis (MESA) participants who underwent cardiac MRI at Visit 1 (2000-02) and Visit 5 (2010-12) and had available Lp(a) at baseline were examined. Lp(a) was analyzed as a continuous and a categorical variable based on quartiles (Q1[<7.6 mg/dL], Q2[7.6-16.7 mg/dL], Q3[16.8-38.8 mg/dL], Q4[>38.8 mg/dL]). Multivariable linear regression analysis was used to examine the association of Lp(a) with changes in cardiac MRI measures of LV remodeling (
Table
).

Results:
Participants had a mean age 60±9 years and 53% were women. Over 10-year follow-up, LV indexed volumes decreased, while LV indexed mass and mass to volume ratio increased across all the Lp(a) quartiles. However, LV ejection fraction only decreased in the third and fourth Lp(a) quartiles. Lp(a) examined as a continuous variable was associated with an increase in LV end-systolic indexed volume (per log-unit Lp[a]; β 0.32 mL/m
2
;
P
= 0.01), LV indexed mass (per log-unit Lp[a]; β 0.38 g/m
2
;
P
= 0.02), and a decrease in LV ejection fraction (per log-unit Lp[a]; β -0.29 %;
P
= 0.02) over 10 years after adjusting for sociodemographic and traditional cardiovascular risk factors (
Table
). Similarly, the fourth Lp(a) quartile was associated with an increase in LV end-systolic indexed volume (β 1.07 mL/m
2
;
P
= 0.01), LV indexed mass (β 1.17 g/m
2
;
P
= 0.02) and a decrease in LV ejection fraction (β -1.01 %;
P
= 0.01) compared to the first Lp(a) quartile after controlling for risk factors. The observed associations remained significant after further adjusting for aortic valve calcium score at Visit 1 (
Table
- Model 3), and baseline coronary artery calcium score and interim myocardial infarction (
Table
- Model 4).

Conclusions:
In a multi-ethnic cohort of participants free of cardiovascular disease at baseline, higher Lp(a) levels were independently associated with an increase in LV end-systolic volume and LV mass as well as a decrease in LV ejection fraction over the span of a decade.
Abstract 4135869: Local Ethanol Infusion after Pulsed Field Ablation Enhances Acute Efficacy of In Vivo Ventricular Electroporation
Authors: Koya Taro , Otsuka Naoto , Tri Jason , ying yang , Sauer William , Asirvatham Samuel , Nguyen Duy
Published: November 2024

Background:
Pulsed field ablation (PFA) has emerged as an innovative technology for treating cardiac arrhythmias. PFA increases cell permeability, which can lead to apoptosis. Greater PFA energy may be necessary to ablate ventricular myocardium for ventricular tachycardia circuits, but this carries risks of side effects such as gaseous formation (microbubbles) and hemolysis. Ethanol (EtOH) infusion has been used to ablate pathologic myocardial tissues in hypertrophic cardiomyopathy and for refractory arrhythmias.

Hypothesis:
We hypothesize that PFA in the ventricle can increase EtOH uptake through PFA-generated pores, thereby enhancing ablation efficacy, even at low powers, by utilizing the cell permeability effects of PFA.

Aim:
The aim of this study is to investigate the effect of local EtOH infusion after PFA on lesion size in porcine ventricles.

Methods:
The ventricles of five porcine subjects were ablated
in vivo
with a PFA low power setting (750 V, at 20 μs for 50 pulses separated by 200 ms) using a focal bipolar irrigated ablation catheter and BTX 830 electroporation generator (Harvard Apparatus). After PFA was performed, 2 ml of 90 % EtOH vs. saline (control) was infused through the catheter tip to the site of ablation. We compared the electrograms voltage amplitude reduction before and after PFA, and the ablation lesion characteristics.

Results:
A total of 10 lesions in the control group and 9 lesions in the EtOH group were analyzed. For the controls, the voltage after PFA was not reduced. In contrast, for the EtOH group, the voltage after PFA was significantly reduced (
Figure 1A
). On gross pathology, there were significant differences in ablation lesion depths and volumes between the 2 lesion sets (
Figure 1A-B
).

Conclusion:
Local EtOH infusion after ventricular PFA enhanced acute efficacy of electroporation. Concurrent PFA with local EtOH infusion has the potential to improve efficacy without requiring higher energy parameters, thereby reducing PFA risks. Future studies on chronic efficacy are warranted.
Abstract 4135893: The Importance of Genetic Testing in Diagnosis and Management of Peripartum Cardiomyopathy: A Case Study
Authors: D'Costa Zoee , Wong Eugene , Zhang Min , Fishbein Gregory , Wang Jessica , Kamath Megan , Shahandeh Negeen
Published: November 2024

Introduction:
At least 15% of women diagnosed with peripartum cardiomyopathy (PPCM) are found to have a pathogenic genetic variant associated with dilated cardiomyopathy. We present a patient with PPCM who required orthotopic heart transplantation (OHT) for cardiogenic shock. Her explant pathology and genetic testing played a critical role in identifying the etiology of her cardiomyopathy.

Case Description:
A 22-year-old primigravid woman with a history of asthma presented in labor and underwent a Cesarean delivery for non-reassuring fetal heart tones. She had noted exertional dyspnea, a dry cough, and orthopnea in her final weeks of pregnancy but had an otherwise uncomplicated pregnancy. Immediately following delivery, she suffered a cardiac arrest with pulseless electrical activity and developed cardiogenic shock. She was found to have severe biventricular systolic dysfunction with a left ventricular (LV) ejection fraction of 10%. She was cannulated on veno-arterial extracorporeal membrane oxygenation (VA-ECMO) and transferred to our center. She was transitioned from VA-ECMO to an axillary Impella 5.5 device but continued to require inotropic support without evidence of LV recovery. Therefore, she was listed for and successfully underwent OHT. Explant pathology (Figure 1) revealed arrhythmogenic cardiomyopathy (ACM). Her family history was significant for a maternal grandfather who died of an unspecified arrhythmia at age 57. Genetic testing via a commercial arrhythmia and cardiomyopathy panel revealed a pathogenic desmoplakin (
DSP)
truncating variant (
DSP
tv) p.Ser1894Leufs*34 in the N-terminal constitutive NMD-competent region, confirming the diagnosis of ACM. The patient had minor cutaneous findings, including curly hair, consistent with the clinical presentation of
DSP
-mediated ACM.

Discussion:
This case highlights the importance of genetic testing in all patients with PPCM, as well as attention to the explant pathology in those who undergo OHT. These practices can elucidate the mechanism of cardiomyopathy, inform the risks of disease progression and of relapse with subsequent pregnancy, and allow for cascade testing of family members.
Abstract 4135923: Predictive Value of Supraventricular Tachycardia on Ambulatory ECG Monitoring for Recurrent Atrial Fibrillation Post-Catheter Ablation
Authors: Sanadgol Ghazal , Ramadan Adham , Alfie Tristan , Yazdanpanah Mohammad Hosein , Nahlawi Acile , Ptaszek Leon , Ruskin Jeremy
Published: November 2024

Introduction:
Established predictors of recurrent atrial fibrillation (AF) following catheter ablation (CA) have not incorporated findings on post-CA ambulatory ECG monitoring (AECG).

Aims:
This study examined the predictive value of supraventricular tachycardia (SVT) detected on 7–14-day AECG for recurrent AF within one year post-CA.

Methods:
This single-center retrospective study included a select subset of patients who underwent CA for AF between 2015 and 2023 and had AECG monitoring within the first year post-CA. SVT presence and characteristics on AECG were analyzed.Data on demographics, AF risk factors, and AF recurrences were extracted from electronic health records. ROC curves determined SVT episode thresholds. A multivariable regression model included established risk factors and SVT thresholds, and best subsets regression identified predictors of AF recurrence.

Results:
Of 7,481 patients undergoing CA for AF, 1,245 were monitored within one year post-CA. Among this subset, 439 (35.26 %) had recurrent AF during the first year post- CA. Of the 439 patients with recurrent AF, 99 had AECG monitoring before recurrence. These 99 patients were compared with the 672 patients with no AF recurrence. Average duration of AECG monitoring for the entire cohort was 11±2.7 days. Mean SVT episodes per day ≥4.6 and total number of SVT episodes ≥14.5 were significantly associated with recurrent AF (OR =1.99, P =0.030, and OR =2.77, P =0.019, respectively). Significant predictors of AF recurrence were female gender, heart failure, confirmed SVT, cardioversion before ablation, mean SVT episodes per day, and total SVT episodes on AECG.

Conclusion:
High burden of SVT on AECG monitoring (defined in this study to be ≥4.6 episode per day or ≥14.5 total episodes per monitoring period) was significantly associated with AF recurrence. Longitudinal studies in larger unselected populations are needed to confirm these results.
Abstract 4135928: Externally Validated Deep Learning Model for Patent Ductus Arteriosus Detection by Echocardiography in Preterm Infants
Authors: Gearhart Addison , Elrod Micaela , Gomes Thomas , Golbus Alexa , Baltimore Christopher , Wakser Cayla , Graham Jason , Lai Wyman , Powell Andrew , Smith Dane , Baker George
Published: November 2024

Introduction:
Patent ductus arteriosus (PDA) is a common form of congenital heart disease in premature infants and a source of significant morbidity. Echocardiography is the mainstay modality for diagnosis and monitoring but is resource-intensive and requires expertise for interpretation.

Aims:
To develop and externally validate a deep learning model to identify PDA in preterm infants by echocardiography.

Methods:
We trained, validated, and tested a convolutional neural network to detect PDA in raw echocardiogram clips from infants (gestational age <37 weeks) with and without PDAs and no significant additional congenital heart disease at the Medical University of South Carolina (MUSC). For training and validation, we employed a 12-fold cross-validation procedure. Experienced cardiologists defined the ground truth labels. We assessed classification performance on an internal model naïve dataset using the area under the receiver operator curve (AUROC), sensitivity, specificity, positive predictive value, and negative predictive value. For external multicenter testing, we used studies from Children’s Hospital of Orange County (CHOC) and Boston Children’s Hospital (BCH), both of which utilize a different ultrasound system vendor.

Results:
Training and validation were completed using 1,145 color/color-compare clips (661 clips with PDA and 484 no PDA) from 66 patients. The internal test dataset consisted of 142 clips from 16 patients. The external CHOC and BCH cohorts consisted of 146 clips from 50 patients and 294 clips from 68 patients, respectively. Model performance was similar for internal and external testing (Table 1).

Conclusions:
Our deep learning model detected the presence of PDA with acceptable performance. This performance generalized well across multiple institutions and ultrasound vendors. This work shows promise for the future development of an automated tool for PDA diagnosis enabling the democratization of pediatric cardiology resources.
Abstract 4135968: Radiomic features of skeletal muscle on prostate T1-Weighted MRI associated with MACE outcomes in prostate cancer patients undergoing hormonal therapy
Authors: Hyma Kunhiraman Harikrishnan , Shiradkar Rakesh , Yerraguntla Sandeep , Gopu Gaurav , Joseph Stanley , Jiang Stephanie , Makram Omar , Weintraub Neal , Mittal Pardeep , Patel Sagar , Modanwal Gourav , Setiadi Natasha , Li Liping , Madabhushi Anant , Guha Avirup
Published: November 2024

Background:
Patients with high-risk prostate cancer (PC) who undergo hormonal therapy(HT) frequently die of major adverse cardiovascular events (MACE). Skeletal muscle on abdominal T1-weighted MRI (T1W) has been shown to be associated with cardiovascular fitness.

Aims:
To quantify heterogeneity associated with skeletal muscle tissue composition on prostate MRI patients undergoing HT using computationally derived radiomic features and identify their association with MACE.

Methods:
Cohort of N=58 men diagnosed with PC who underwent a 3 Tesla pre-treatment multi-parametric MRI followed by HT and followed up for MACE events were identified. MACE is defined as a composite of cardiovascular death, atrial fibrillation, myocardial infarction, ischemic stroke, heart failure, coronary artery disease, and peripheral vascular disease. Regions of interest (ROI) of skeletal muscle, including the obturator externus, pectineus, and the adductor group of muscles, were delineated on axial T1W under the guidance of an experienced radiologist. A set of 120 radiomic features, including gray level statistics, co-occurrence, wavelet, and texture energy-based features, were extracted within the ROI which quantifies underlying subvisual texture-based heterogeneity. Radiomics associated with MACE events were identified using the Wilcoxon rank-sum test and univariate Cox-regression (p<0.05).

Results:
Of the N=58 patients included in this study, 18 experienced MACE. The most common MACE event was AF (8.6%). Median-time-to-MACE event was 7.3 years (6.2-8.2). 3 radiomic features (Table 1) quantifying the heterogeneity of skeletal muscle on prostate T1W were observed to be associated with MACE. Specifically, we observe that first order features have a lower response and wavelet features have a lower response in MACE patients which suggests a higher degree of local deformations and heterogeneity in skeletal tissue compared to non-MACE patients.

Conclusions:
Results from our study suggest that radiomics quantified texture characteristics of skeletal muscle tissue may indicate cardiovascular fitness, reflecting the likelihood of experiencing MACE following initiation of HT in PC men. Pre-treatment identification of PC patients at high risk of MACE may allow for alternative treatment options improving cardiovascular outcomes. Future studies will involve exploring larger, multi-site cohorts and machine learning modeling to determine cardiovascular risk.
Abstract 4136013: Pre-operative Frailty Status and Short-term Complications Among Adults Undergoing Transcatheter Aortic Valve Replacement
Authors: Dhaliwal Jasninder , Kumar Nomesh , johal parampreet , Ramphul Kamleshun , Singla Rahul , Dhaliwal Kanwar Bir Singh , Verma Renuka , Sekhon Manraj , Rajotia Arush , Sakthivel Hemamalini
Published: November 2024

Introduction:
The use of Transcatheter Aortic Valve Replacement(TAVR) has provided a safer alternative to open surgical approaches. The introduction of frailty scoring systems has proven effective in improving healthcare approaches and outcomes in various aspects of medicine. As there is a paucity of data on the impact of frailty among TAVR patients, we aim to conduct a retrospective study to investigate further.

Methods:
Our study analyzed adult cases with a primary procedural code for TAVR among hospitalizations between 2016 and 2021 through the National Inpatient Sample(NIS). Frailty status was explored through the criteria of Gilbert’s frailty index. Multivariable regression models helped evaluate differences in short-term outcomes and complications between them.

Results:
Our study involved 374200 cases of TAVR that were divided into LFR(285425 cases, 76.3%), IFR(86005 cases, 23.0%), and HFR(2770 cases, 0.7%). Compared to patients with LFR, patients with MFR and HFR showed higher odds of several complications, including cardiogenic shock(MFR: aOR 6.933, p<0.001, HFR: aOR 13.303, p<0.001), acute kidney injury(MFR: aOR 9.737, p<0.001, HFR: aOR 26.685, p<0.001 ), use of invasive mechanical ventilation(MFR: aOR 10.763, p<0.001,HFR: aOR 39.432, p<0.001), events of acute myocardial infarction(MFR: aOR 3.32, p<0.001, HFR: aOR 6.021, p<0.001), need for transfusion of blood products(MFR: aOR 3.027, p< 0.001, HFR: aOR 5.938,p<0.001), post-procedural bleeding(MFR: aOR 2.475, p<0.001, HFR: aOR 3.277, p<0.001), IABP use(MFR: aOR 4.942, p<0.001, HFR: aOR 9.703, p<0.001), and need for pericardiocentesis(MFR: aOR 3.804, p<0.001, HFR: aOR 4.217, p<0.001). Moreover, patients with MFR and HFR reported higher mortality risks than those with LFR(MFR: aOR 6.375, p<0.001, HFR: aOR 16.035, p<0.001 )(Table 1).

Conclusion:
Our study confirms the higher odds of various complications with increasing frailty status, including all-cause in-hospital death. A careful assessment of pre-operative frailty status along with close monitoring of pre-, peri-, and post-operative status will help improve the outcomes and provide care in a timely fashion.
Abstract 4136169: Phenotypic clustering of right heart dilatation in pulmonary arterial hypertension
Authors: Celant Lucas , Wessels Jeroen , meiboom lilian , Marcus J. Tim , Bogaard Harm , Strijkers Gustav , Handoko M , Vonk Noordegraaf Anton , De Man Frances
Published: November 2024

Introduction:
Right ventricular (RV) and right atrial (RA) dilatation are important hallmarks of disease severity in patients with pulmonary arterial hypertension (PAH). To obtain more insights on the clinical significance of RA dilatation, we phenotypically characterized patients with right heart dilatation.

Aim:
Description of different RV/RA phenotypes in PAH

Methods:
203 incident, treatment naïve PAH patients with cardiac magnetic resonance (CMR) imaging were included. Phenotypic clustering was based on RA and RV dilatation. Conform literature, RA dilatation was defined by a RA index maximal area >15 cm
2
/m
2
. RV dilatation was defined by an RVEDV/LVEDV ratio >1.3 and >2.4 for extreme dilatation.

Results:
Four phenotypic patient clusters were identified: no dilatation (n=48), RV dilatation (n=78), RV+RA dilatation (n=53) and extreme RV dilatation + RA dilatation (n=23), Figure 1A. To unravel the additive clinical value of RA dilatation, we mainly compared patients with RV dilatation and patients with RV+RA dilatation. Intriguingly, patients with RV+RA dilatation demonstrated lower 3- and 5-year survival rates (58% and 43% vs. 75% and 55%) (Figure 1B) and were less likely to reverse RV dilatation after treatment initiation than patients with RV dilatation only. Despite the consequences of RA dilatation, we could not identify an explanation for the difference in RA dilatation between both groups. No difference in afterload was observed, shown by comparable pulmonary vascular resistance (9.9 [6.8-13] WU vs. 10 [7.5-12.3] WU, p>0.05). RV function was similarly impaired (RV ejection fraction: 36±9% vs. 33±9%, p>0.05). End-diastolic elastance (0.73 [0.39-1.11] mmHg/mL vs. 0.58 [0.40-0.94] mmHg/mL, p>0.05) and severity of tricuspid regurgitation did not differ. Finally, diuretic use (40% vs. 40%, p>0.05), age (54±16 vs. 57±19 yrs, p>0.05), female gender (70% vs. 60%, p>0.05) and iPAH diagnoses was similar (69% vs. 59%, p>0.05).

Conclusion:
PAH-patients with both RA and RV dilatation have a worse clinical profile than patients with only RV dilatation. However, no clear trigger for RA dilatation was found and future mechanistic studies should unravel factors explaining these differences in right heart adaptation.
Abstract 4136289: Aortic Valve Calcium as a Predictor of Chronic Kidney Disease in a Multi-Ethnic Cohort: The MESA Study
Authors: Abdollahi Ashkan , Sani Maryam , Shabani Mahsima , Scarpa Bruna , Blaha Michael , Wu Colin , Ambale-Venkatesh Bharath , Budoff Matthew , Strom Jordan , Rotter Jerome , Post Wendy , Blumenthal Roger , Bluemke David , Lima Joao AC , Whelton Seamus
Published: November 2024

Background:
Aortic valve calcium (AVC) is associated with an increased risk of cardiovascular disease, non-cardiovascular disease such as dementia, and all-cause mortality. Traditional atherosclerotic cardiovascular disease risk factors are associated with both AVC and chronic kidney disease (CKD), but whether there is an association between AVC and CKD is unknown.

Objectives:
To ascertain whether AVC quantified by cardiac CT scanning is independently associated with the long-term risk of incident CKD among individuals without a previous history of cardiovascular disease.

Methods:
We examined 6,346 Multi-Ethnic Study of Atherosclerosis (MESA) participants who underwent cardiac CT scanning at Visit 1 (2000-02) and had an eGFR of ≥ 60 mL/min/1.73 m
2
. AVC was quantified using the Agatston method and categorized as 0, 1-99, and ≥100. Incident CKD was defined as an eGFR < 60 mL/min/1.73 m
2
accompanied with an at least 40% decline in eGFR from baseline, and/or a diagnosis of CKD and indicators of end stage renal disease extracted from hospital records using the International Classification of Disease (ICD) codes. We performed Kaplan-Meier survival curve analyses along with multivariable Cox proportional hazard regression models, adjusted for age, gender, race/ethnicity, highest level of education and traditional cardiovascular risk factors along with coronary artery calcium (CAC), lipoprotein (a) (Lp[a]), and the APOE-ε4 genotype to examine the association between AVC (categorical and log-transformed) and incident CKD.

Results:
Participants had a mean age 62.2±10.1 years, 53% were women, and AVC >0 was present in 795 (12%) participants. During a median follow-up time of 16.9 years, 982 (15%) participants developed incident CKD. AVC examined as a continuous variable was associated with a significantly increased risk of developing CKD (per log-unit [AVC+1] HR 1.06 [95% CI: 1.02-1.10];
p
= 0.005). There was a stepwise increased risk for CKD with higher AVC levels (
Figure
). Similarly, in the multivariable adjusted Cox models, participants with AVC ≥100 had a higher risk of incident CKD, compared with the AVC=0 group (HR 1.48 [95% CI: 1.15-1.89];
p
= 0.002). The observed associations remained after further adjusting for CAC score (
p
= 0.024), Lp (a) (
p
= 0.004), and the APOE-ε4 genotype (
p
= 0.004).

Conclusions:
In a multi-ethnic cohort of participants free of CKD at baseline, AVC was independently associated with a higher risk of incident CKD.
Abstract 4136290: Toward Quantitative Assessment of Cerebrovascular Autoregulation in Neonates using Ultrafast Ultrasound Power Doppler
Authors: Fakhari Nikan , Aguet Julien , Nguyen Minh , Mertens Luc , Crawford Lean Lynn , Haller Christoph , Barron David , Sled Jonh , Baranger Jerome , Villemain Olivier
Published: November 2024

Introduction:
Newborns with congenital heart diseases requiring cardiopulmonary bypass are at risk of neurodevelopmental impairment. The impact of deep hypothermia during cardiopulmonary bypass (DH-CPB) on cerebrovascular autoregulation (CAR) that controls brain perfusion in the presence of variable blood pressure is not well understood. Recently, Ultrafast Power Doppler (UPD) showed potential to study CAR in neonates based on the measurement of cerebral blood volume (CBV). However, since CAR relies mainly on the arterial vasoconstriction/vasodilation, the interpretation of brain perfusion based on CBV requires further separation of arterial CBV from total CBV. This study aims to use UPD to monitor CAR during DH-CPB in neonates.

Methods:
An ultrasonic probe (5.7 MHz) was placed on the anterior fontanel of 6 newborns before, during and after DH-CPB. Using ultrafast sequences generated by a Verasonic Vantage research system, mid-coronal plane images were acquired (PRF of 9 kHz, 5 compounded diverging waves). An adaptive spatiotemporal singular value decomposition was used to separate the blood signal from tissue signal and obtain UPD. CBV was computed in the deep gray matter (DGM). This region was chosen due to its higher susceptibility to hypoxic-ischemic injury. Arterial CBV was isolated from total CBV based on the upward arterial flow obtained using signed-power Doppler (See Fig A). Pearson correlation ® was computed between mean arterial blood pressure (MAP) and arterial CBV to study CAR.

Results:
Before and after DH-CPB, negative correlations were found between arterial CBV and MAP: -0.30 and -0.43 respectively. This indicates that an increase in MAP is associated with a decrease in cerebral arterial blood volume. This decrease in arterial CBV likely arises from arterial vasoconstriction, suggesting an active CAR response. Conversely, during DH-CPB, no correlation was found (r = -0.02). This means that despite the increase in MAP, arterial CBV remains unchanged. This lack of variation of arterial CBV is likely due to absent arterial vasoconstriction, suggesting an impaired CAR response.

Conclusion:
Our findings highlight the potential of UPD for continuous monitoring of CAR, paving the way for improving neurovascular management strategies during DH- CPB.
Abstract 4136448: A Novel Cardiomyocyte Targeting Peptide Enhances Calcium Handling
Authors: Lopuszynski Jack , Wang Jingyu , Dyer Roy , Sahagun Daniella , Zahid Maliha
Published: November 2024

Introduction:
Intracellular calcium handling plays a central role in cardiac contractility and relaxation. Genes such as the Ca
2+
-ATPase pump (SERCA2a) and the Dihydropteridine reductase (DHPR) enzyme are especially important in the cycling of intracellular calcium. As prior research has established a link between treatment with our cardiac targeting peptide (CTP: a 12-amino acid, cardiomyocyte-specific cell penetrating peptide) and upregulation of calcium-handling genes such as SERCA2a and DHPR, we hypothesized that treatment with our novel hybrid cardiac targeting peptide (hCTP: positions #3 and 11 replaced with the D-enantiomer form of the amino acids) will improve intracellular calcium handling in human cardiomyocytes (CMCs) by increasing expression of key calcium handling genes instrumental in sequestering calcium in diastole and lowering cytosolic levels.

Methods:
To test hCTP’s calcium handling abilities, CMCs were plated on day 1 and allowed to settle for 24 hours, after which they received daily treatment with various concentrations of hCTP (1-25µM) for three days. On day 5, cells underwent either intracellular calcium measurements using the FLIPR 6 Calcium assay or were prepared for western blotting. Western blotting was performed to determine the protein concentrations of SERCA2a and DHPR, as compared to a GAPDH control. To test hCTP’s intrinsic calcium handling abilities, various concentrations of hCTP were mixed with a constant amount of elemental calcium dissolved in water. After 20 min at 37
o
C, the concentration of free Ca
2+
was measured with an ABL90 Flex Plus radiometer.

Results:
In CMCs, treatment with hCTP led to a decrease in cytosolic calcium in a dose dependent fashion; concentrations as low as 1µM led to a significant decrease in cytosolic calcium (p< 0.0001 for all groups). Western blots performed on the treated CMCs revealed an increase in expression of both DHPR and SERCA2a, normalized to GAPDH control. Outside of the cellular environment, hCTP did not appear to display inherent calcium sequestring properties, suggesting that improvements in calcium handling are due to upregulation of gene expression.

Conclusion:
hCTP appears to lower cytosolic calcium and improve calcium handling through upregulation of SERCA2a and DHPR. Our data indicates that hCTP is worth pursuing as a stand-alone, cardio-selective therapy for cardiomyopathies involving calcium mishandling.
Abstract 4136532: The Agonism of Macrophage Migration Inhibitory Factor Modulates Neutrophils Subsets and Rescues an Impaired Tolerance to Ischemic Insults in Aging
Authors: Wang Hao , Punati Shriya , Slotabec Lily , Seale Blaise , Rouhi Nadiyeh , Filho Fernanda , Adenawoola Michael , Li Ji
Published: November 2024

Introduction:
An impaired cardiac macrophage migration inhibitory factor (MIF) signaling in aging during ischemia and reperfusion (I/R) can be rescued by a MIF agonist, MIF20. Alterations in cardiac metabolic homeostasis cause inflammation under I/R. Thus, MIF agonism with MIF20 could modulate cardiac inflammatory response during I/R.

Hypothesis:
MIF20 modulates the polarization of neutrophil subset and rescues the impaired immune response under I/R in aging.

Methods:
Young (3-months)/aged (24 months) C57BL/6 wild type (WT) mice and MIF

flox/flox

(3 months)/cMIF
-/-
(cardiomyocyte MIF deletion, 3 months) were subjected to LAD ligation of for 45 min of ischemia, followed by 24 hr of reperfusion. MIF20 (0.15 µg/kg, i.v.) was injected at 5 minutes before reperfusion. The immune cells were determined with flow cytometry. mRNA and protein were measured by real-time qPCR, immunoblotting/cytokine array.

Results:
Administration of MIF20 reduced myocardial infarct by I/R in young/aged WT and MIF

flox/flox

but not in cMIF
-/-
mice. The flow cytometry showed that I/R stress dramatically triggered neutrophils infiltration, which occurred in both left ventricle and right ventricle. Intriguingly, MIF20 treatment reduced the I/R-induced neutrophil recruitment in hearts. Aged versus young WT myocardium recruited more N1 neutrophils (CD206
-
), while MIF20 treatment rescued the impaired N1 neutrophils response in aging. Moreover, MIF20 can increase infiltration of N2 neutrophils (CD206
+
) in both young and aged WT hearts. The recombinant MIF can directly trigger N2 neutrophil polarization and N1 neutrophil reduction in cMIF
-/-
hearts, indicating the critical role of MIF/CD74 axis in neutrophil polarization by I/R challenge. The cytokine array showed that MIF20 treatment can trigger cardiac TGF-β levels and upregulate IL-10 levels in serum under I/R, since TGF-β and IL-10 are critical factors involved in the N2 neutrophils’ polarization. Interestingly, MIF20 increased SiglecF marker on neutrophils in the aged versus young hearts, suggesting that MIF20 rescue the long-lived neutrophil population (SiglecF
high
) which could enhance phagocytosis to repair damaged myocardium during I/R conditions.

Conclusions:
An impairment of metabolic homeostasis and inflammatory response occurred in cardiac aging. MIF agonism with small molecule MIF20 can rescue the capacity of MIF/CD74 signaling to maintain metabolic homeostasis and inflammatory response in aging under I/R pathological conditions.
Abstract 4136584: The Association of De Novo Niacin Use with Long-Term Mortality
Authors: Takahashi Rina , Bui Thuy-Anh , Elali ibrahim , Tran Diana , SUMIDA KEIICHI , Thomas Fridtjof , Dukkipati Ramanath , shah anjja , Rhee Connie , Kovesdy Csaba , Kalantar-Zadeh Kamyar
Published: November 2024

Introduction:
Niacin is a non-statin lipid-lowering therapy that has been shown to lower triglycerides and improve other risk factors for cardiovascular diseases. However, previous studies have reported inconsistent effects of niacin on mortality, and its effect on long-term prognosis has not been well studied.

Goals:
The aim of this study is to examine the association of niacin therapy with long-term all-cause mortality.

Methods:
In a nationwide historical cohort of 1,139,630 US Veterans with normal baseline kidney function, we examined the association of de novo niacin prescription from 2004 to 2006 with all-cause mortality during a 14-year follow-up. Associations were examined in Cox proportional hazard models adjusted for demographics, major comorbidities, and laboratory measurements. Prescription time-distribution matching was used to control for survival bias.

Results:
We identified 133,450 new users of niacin. Overall, patients had a mean (standard deviation) age of 60 (13) years, with 6% female, 78% White, 16% Black, and 6% Hispanic. Niacin users were more likely to be male, White, current, or former smokers and had higher frequencies of comorbidities. Niacin use (vs. non-use) was associated with a lower risk of death (Hazard ratio: 0.89, 95% confidential interval: 0.88-0.90) in the fully adjusted model (Model 4, Figure).

Conclusion:
In a large national cohort of US Veterans, niacin use was associated with a lower risk of death. Further studies are needed to corroborate the potential benefits of niacin on survival.
Abstract 4136636: Analysis of Racial Disparities in the Training Path to Cardiology: Trends from 2012 to 2022
Authors: Gopal Jay , Rahafrooz Maryam , Chan Nathan , Gopal Devraj , Kepler Joshua , Ren Junling , Gopal Indulekha , Joseph Jacob
Published: November 2024

Introduction:
Substantial evidence indicates that racial and ethnic diversity among the physician workforce bridges cultural gaps and improves patient care. Trends in racial diversity across the full training pipeline from undergraduate to practicing cardiologist are not yet well-characterized.

Aims:
We analyze racial disparities at each stage of training towards becoming a practicing cardiologist, and identify changes in these disparities between 2012 and 2022.

Methods:
We conducted a retrospective analysis of data specifying the racial composition of medical trainees acquired from the Association of American Medical Colleges, Accreditation Council for Graduate Medical Education, and Electronic Residency Application Service. Population data was acquired from the US Census Bureau. We computed the representation quotient (RQ) for each racial group at each stage to compare representation among the trainees or physicians to age-matched segments of the US population.

Results:
RQ decreases from undergraduate to active cardiologist for African Americans (0.719 to 0.314), Hispanics (0.660 to 0.359), American Indians (0.551 to 0.221), and Native Hawaiians (1.121 to 0.512). The lowest RQs of 0.133 and 0.137 were observed for American Indian active internal medicine residents and cardiology fellows, respectively. Racial disparities in medical education declined between 2012 and 2022, with RQs increasing from 0.541 to 0.735 for African American medical school matriculants and from 0.444 to 0.578 for Hispanic medical school matriculants. Similar increases were seen in the active cardiologist population for African Americans (2013 RQ: 0.227, 2022 RQ: 0.342) and Hispanics (2013 RQ: 0.283, 2022 RQ: 0.375).

Conclusion:
While racial diversity in the cardiology training pipeline has increased over the last decade, significant disparities persist for under-represented minorities. Addressing these barriers will help achieve a cardiology workforce reflective of the diverse population it serves.
Abstract 4136654: Urine Output Response to a Furosemide Infusion is Associated with Acute Kidney Injury in Infants Following Cardiac Surgery
Authors: Pierick Alyson , Luckritz Kera , Huebschman Ashley , Duimstra Ashley , Yu Sunkyung , Sznycer-Taub Nathaniel
Published: November 2024

Background:
Acute kidney injury (AKI) following cardiac surgery in infants is common and associated with longer mechanical ventilation times and length of stay. Prior studies have shown that a lack of responsiveness to bolus dose furosemide has been associated with increased incidence of AKI. However, these studies have excluded patients on continuous furosemide infusions who are often younger, more hemodynamically unstable, and at higher risk for AKI.

Hypothesis:
Decreased urine output after initiation of a furosemide infusion predicts development of AKI.

Methods:
A retrospective cohort study of infants (<1 year of age) was conducted who underwent cardiac surgery requiring cardiopulmonary bypass from 2020-2023 and were on a furosemide infusion post-operatively. The primary outcome was post-operative AKI as defined using KDIGO (Kidney Disease: Improving Global Outcomes) guidelines. A furosemide response score (FRS) was calculated using the total urine output divided by the total dose of furosemide administered over a given time. Univariate and multivariate analyses were performed, and receiver operating characteristic curves used to determine the discriminatory ability of the FRS with regards to the primary outcome.

Results:
A total of 155 infants (median age at surgery 9 days) were included. Overall, 77% of infants met definition for the primary outcome of AKI; 32% stage 1, 30% stage 2, and 15% stage 3. Lower FRS at 4, 10, and 24 hours after infusion initiation were associated with AKI development (p<0.0001). Younger age, smaller weight at surgery, lack of pre-operative feedings, pre-operative inotropic use and higher surgical complexity were also associated with a higher risk of AKI. An FRS (mL/mg/kg) cutoff of <11.3 at 4 hours, <25.5 at 10 hours, and <55.3 at 24 hours had good discriminatory ability (area under the curve 0.7-0.75) in predicting AKI stage 2 or 3 (p<0.001). Controlling for the significant univariate variables listed above, the FRS cutoffs remained an independent risk factor for the development of AKI stage 2 or 3, (p<0.01) and were significantly associated with longer mechanical ventilation days and length of stay.

Conclusion:
Lack of responsiveness to a furosemide infusion (as measured by urine output corrected for dose of furosemide) is associated with the development of AKI in a high-risk cohort of infants. These novel findings may be helpful to predict those at risk and allow for further investigations for modifiable risk factors.
Abstract 4136678: Detecting Myosteatosis-Related Low Physical Function in Heart Failure Patients Using Abdominal Computed Tomography and Plasma Amino Acid Profile
Authors: Kawaharata Wataru , Kouzu Hidemichi , Ogura Keishi , Yano Toshiyuki , Katano Satoshi , Nagaoka Ryohei , Numazawa Ryo , Yamano Kotaro , Ohori Katsuhiko , Nishikawa Ryo , Fujito Takefumi , Nobutaka Nagano , Furuhashi Masato
Published: November 2024

Background:
Evaluation of sarcopenia requires quantifying appendicular skeletal muscle mass and functional capacity, but resource constraints often limit feasibility. Alterations in muscle quality, especially intramuscular lipid infiltration (i.e., myosteatosis), and systemic metabolic derangements are associated with disability.

Hypothesis:
Opportunistic CT imaging and plasma amino acid profiling could identify low physical function in patients with heart failure (HF).

Methods:
We retrospectively examined 220 HF patients (74 ± 13 years old; 59% male) who underwent plasma amino acid profiling, abdominal CT imaging, and dual-energy X-ray absorptiometry (DXA) scan within two months. Myosteatosis was evaluated using single-slice CT imaging at the L3/4 level and quantified as mean muscle attenuation (MMA). Physical function was assessed by the short physical performance battery (SPPB), with low physical function defined as SPPB ≤9.

Results:
CT-derived single-slice areas of skeletal muscle and adipose tissue were highly correlated with DXA-derived appendicular skeletal muscle mass and total fat mass. Logistic regression analyses revealed that higher age and lower MMA, but not skeletal muscle area, were significantly associated with low physical function independently of NT-proBNP. Subjects with MMA below the median value (32.0 HU for males and 23.7 HU for females) had higher odds of low physical function (adjusted OR 2.04, 95% CI 1.04-3.96). Ten amino acids and the Fischer ratio were significantly correlated with MMA levels. Multivariate regression analyses, adjusted for potential confounders including age, gender, and body mass index, demonstrated that serum albumin and Fischer ratio were independent determinants of MMA levels. When serum albumin and Fischer ratio were dichotomized by their median values (3.6 mg/dL and 3.23, respectively), the prevalence of low physical function was significantly higher in subjects with low albumin and low Fischer ratio, but not in those with low levels of only either parameter, compared to those with high albumin and high Fischer ratio (adjusted OR 2.36, 95% CI 1.02-5.49).

Conclusions:
Myosteatosis assessed by single-slice abdominal CT imaging is an independent determinant of low physical function in HF patients. Combined with an assessment of serum albumin and Fischer ratio, these simple biomarkers could facilitate the early detection of patients at risk for developing frailty.
Abstract 4136687: VTRNA2-1 Promoter Methylation as a Prognostic Biomarker in Peripheral Artery Disease: Implications for Maternal Nutritional Influence
Authors: Tsai Ming-lung , Huang Yi-Chun , Wang Chao-Yung
Published: November 2024

Background:
Peripheral artery disease (PAD) is associated with high morbidity and mortality and is closely related to diabetes mellitus (DM) and atherosclerosis. Recent advances in epigenetics have highlighted the critical relationships of non-coding RNA Vault RNA 2-1 (VTRNA2-1) promoter methylation and periconceptional nutritional status. Furthermore, the abundance of methylation of the VTRNA2-1 promoter is associated with glucose metabolism and cell aging. This study investigates the association between VTRNA2-1 promoter methylation and clinical outcomes in PAD patients requiring revascularization.

Hypothesis:
VTRNA2-1 promoter methylation status is associated with clinical outcomes in PAD patients requiring revascularization.

Methods:
A total of 133 PAD patients requiring revascularization were enrolled. Inclusion criteria included adults over 20 years old, consent to participate, and a requirement for angioplasty. Blood samples were processed to isolate leukocytes, and DNA was extracted using the DNeasy blood kit. Bisulfite pyrosequencing was performed to quantify CpG site-specific DNA methylation at the VTRNA2-1 promoter locus. General population samples from the National Health Research Institutes were used as the control group to compare the methylation status. Patients' one-year clinical outcomes were evaluated.

Results:
The study found significant differences in VTRNA2-1 promoter methylation status between PAD patients and the control group (P < 0.001). Hypomethylation of VTRNA2-1 promoter was associated with a higher amputation rate in PAD patients (HR 2.19, 95% CI 1.09-4.42, p=0.027). Among patients without ESRD (N=79), those with hypomethylation had a significantly increased risk of major adverse limb events (MALE) (HR 2.78, 95% CI 1.11-6.97, p=0.024), amputations (HR 2.58, 95% CI 1.02-6.57, p=0.044), and progression to ESRD (p=0.039).

Conclusion:
The methylation status of VTRNA2-1 promoter is significantly different between PAD patients and the normal population, with hypomethylation linked to poorer clinical outcomes in PAD patients undergoing revascularization. These findings suggest that VTRNA2-1 promoter methylation status could serve as a valuable biomarker for predicting prognosis and guiding treatment strategies in PAD. Our results open a molecular link between the periconceptional environment and the risks of PAD.