bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 13922: Echocardiography During Resuscitation: A Paradox of Right Ventricular Dilatation in Cardiac Arrest Caused by Hypovolemia and Hyperkalemia - A Randomized Porcine Study
Authors: Aagaard Rasmus , Granfeldt Asger , Klausen Troels M , Kirkegaard Hans , Bøtker Morten T , Løfgren Bo
Published: April 2024

Introduction:
The interpretation of echocardiographic findings from patients with spontaneous circulation is often extrapolated to cardiac arrest. In patients with spontaneous circulation, severe hypovolemia causes a reduction in right ventricular (RV) diameter, which may persist during cardiac arrest. In contrast, hyperkalemia may cause RV dilation by arresting the heart in diastole. Also, animal studies have demonstrated RV dilation in ventricular fibrillation (VF).

Aim:
To study the RV diameter during resuscitation from cardiac arrest caused by hypovolemia and hyperkalemia, compared to VF as control.

Methods:
Twenty-four pigs were randomized to 7 min. of cardiac arrest induced by hypovolemia, hyperkalemia, or VF. Animals were resuscitated in accordance with the AHA 2010 Advanced Life Support guidelines. Echocardiographic images were obtained before and during cardiac arrest. Primary endpoint: RV diameter at the third rhythm analysis.

Results:
In the hypovolemia group, an initial decrease in RV diameter during induction of cardiac arrest was followed by an abrupt increase at the onset of cardiac arrest. Onset of cardiac arrest also increased RV diameter in both the hyperkalemia and VF group (P<0.01 for all) (Figure). At third rhythm analysis, the RV was dilated in all groups compared with baseline (P<0.05). In the hypovolemia group, RV diameter was 32mm (95%CI 29-35) and significantly larger than in the VF group at 25mm (95%CI 22-28) (P=0.008). In the hyperkalemia group, RV diameter was 29mm (95%CI:26-32) which was not different from hypovolemia and VF (P=NS).

Conclusion:
The right ventricle is dilated during resuscitation from cardiac arrest caused by hypovolemia, hyperkalemia, and ventricular fibrillation. The interpretation of echocardiographic findings in the patient with spontaneous circulation should not be extrapolated to cardiac arrest. Right ventricular dilation may be a feature inherent to cardiac arrest, rather than specific to a certain cause.
Abstract 13984: Extracorporeal Cardiopulmonary Resuscitation for Unwitnessed Cardiac Arrest
Authors: Kagawa Eisuke , Dote Keigo , Kato Masaya , Sasaki Shota , Oda Noboru , Nakano Yoshinori , Nagai Michiaki , Kihara Yasuki
Published: April 2024

Extracorporeal Cardiopulmonary Resuscitation for Unwitnessed Cardiac Arrest

Introduction:
An unwitnessed cardiac arrest has worse prognosis compared to a witnessed cardiac arrest. Extracorporeal cardiopulmonary resuscitation (ECPR) using venoarterial extracorporeal membrane oxygenation (ECMO) may improve outcomes for patients after cardiac arrest.

Hypothesis:
We assessed the hypothesis that ECPR will improve patient outcomes following an unwitnessed and refractory cardiac arrest.

Methods:
Patients who were treated with ECPR were enrolled in this study. We divided the patients into two groups based on whether their cardiac arrest was witnessed or unwitnessed. We assessed baseline patient characteristics, 30-day survival, and neurological outcomes.

Results:
The patients age in years (median 65 [interquartile range 56 - 72] vs. 60 [50 - 74], P = 0.74) and the rate of initially recorded shockable rhythms (39% vs. 33%, P = 0.70) were similar between the patients in the witnessed group (N = 172) and those in the unwitnessed group (N = 15). The duration of cardiopulmonary resuscitation was longer for patients in the unwitnessed group than for those in the witnessed group (66 [44 - 77] min vs. 45 [24 - 62] min, P = 0.004). The rates of performing immediate coronary angiography (75% vs. 87%, P = 0.53), coronary revascularization (44% vs. 33%, P = 0.44), and targeted temperature management (55% vs. 47%, P = 0.55) were similar between the two groups. The rate of return of spontaneous heart beat (91% vs. 60%, P = 0.003) was lower in the unwitnessed group. The rates of weaning from ECMO (44% vs. 27%, P = 0.19) were similar between the two groups. The 30-day survival curves are shown in Figure. There were no favorable neurological outcomes (Cerebral Performance Category scale of 1 or 2) in the unwitnessed group.

Conclusions:
ECPR may not improve patient outcome following unwitnessed arrest even in patients who were initially found to have a shockable rhythm.
Abstract 16649: Recovery of Myocardial Perfusion After Percutaneous Coronary Intervention of Chronic Total Occlusions is Comparable to Non-Occlusive Lesions
Authors: Schumacher Stefan P , Driessen Roel S , Stuijfzand Wijnand J , Raijmakers Pieter G , Danad Ibrahim , Dens Jo , Spratt James C , Hanratty Colm G , Walsh Simon J , Boellaard Ronald , van Rossum Albert C , Opolski Maksymilian P , Nap Alexander , Knaapen Paul
Published: April 2024

Background:
The benefits of chronic coronary total occlusion (CTO) percutaneous coronary intervention (PCI) are being questioned. The aim of this study was to assess the effects of CTO PCI on absolute myocardial perfusion, as compared to PCI of hemodynamically significant non-occlusive lesions.

Methods:
Consecutive patients with a preserved left ventricular ejection fraction (≥50%) and a CTO or non-CTO lesion, in whom [
15
O]H
2
O positron emission tomography was performed prior and after successful PCI, were included. Change in quantitative (hyperemic) myocardial blood flow (MBF), coronary flow reserve (CFR) and perfusion defect size (in myocardial segments) were compared between CTOs and non-occlusive lesions.

Results:
Ninety-two patients with a CTO and 31 patients with a non-occlusive lesion were included. CTOs induced larger perfusion defect sizes (4.51±1.69 vs. 3.23±2.38 segments, p<0.01) with lower hyperemic MBF (1.30±0.37 vs. 1.58±0.62 mL·min
-1
·g
-1
, p<0.01) and similarly impaired CFR (1.66±0.75 vs. 1.89±0.77, p=0.17) compared with non-occlusive lesions. After PCI both hyperemic MBF and CFR increased similarly between groups (p=0.57 and p=0.35) to normal ranges with higher hyperemic MBF values in non-CTO compared to CTO (2.89±0.94 vs. 2.48±0.73 mL·min
-1
·g
-1
, p=0.03). Perfusion defect sizes decreased similarly after CTO PCI and non-CTO PCI (p=0.14), leading to small residual defect sizes in both groups (1.15±1.44 vs. 0.61±1.45 segments, p=0.054).

Conclusions:
Percutaneous revascularization of CTOs improves absolute myocardial perfusion similarly to PCI of hemodynamically significant non-occlusive lesions, leading to satisfying results. Myocardial perfusion findings are less favorable in patients with a CTO before and after PCI, suggesting a more advanced stage of coronary artery disease.
Abstract 16661: Circulating microRNAs as Prognostic Biomarkers in Single Ventricle Heart Disease
Authors: Nakano Stephanie J , SooHoo Megan , Karimpour-Fard Anis , Korst Armin , Pauly Kristine , Phelps Christina M , Michael Alix , Mackey Ann , Miyamoto Shelley D , Sucharov Carmen C
Published: April 2024

Introduction:
Despite significant improvements in surgical technique and post-surgical management, mortality remains high for infants with single ventricle congenital heart disease (SV) and the ability to risk-stratify infants with SV is limited. microRNAs (miRs) are short regulatory RNAs that modulate gene expression and miRs in the circulation are increasingly recognized as valuable biomarkers in a broad range of diseases.

Hypothesis:
Circulating miR profiles prior to surgical palliation may correlate with SV survival at one year and assist with risk-stratification in this population.

Methods:
Serum samples from subjects with SV (of right ventricular morphology) were obtained at the following time points: Pre-Norwood (n=71), Pre-Glenn (n=46) and Pre-Fontan (n=25). Outcomes were classified as alive versus death or heart transplant listing by one year of age. Serum was subject to three freeze/heat cycles to maximize miR release, then miRs were reverse transcribed using a pool of primers specific for each miR. Real-time PCR was performed in 384-well plates containing sequence-specific primers and TaqMan probes in the ABI7900HT.

Results:
Random forest analysis of Pre-Norwood samples demonstrates downregulation of miRs-194, -15b and -193b in patients who died or required heart transplant listing (n=22) compared to those who were alive (n=49). Hierarchical clustering based on these 3 specific miRs is demonstrated in Figure 1 (blue = alive, red = death/transplant). miRs-483-5p, -140-3p and -30b are differentially expressed between the Pre-Norwood, Pre-Glenn, and Pre-Fontan groups and are associated with each surgical stage.

Conclusions:
Circulating miRs demonstrate promise as prognostic biomarkers of 1-year outcome in the Pre-Norwood SV population. Circulating miR profiles are also distinct at each surgical stage. Notably, the identified miRs are known to regulate gene expression in other forms of heart disease and warrant further investigation.
Abstract 16715: Troponin I Levels Correlate With Cardiac Magnetic Resonance Late Gadolinium Enhancement and Native T1 Values in Duchenne Muscular Dystrophy Cardiomyopathy and Identify Early Disease Progression
Authors: Voleti Sonia , Olivieri Laura , Hamann Karin , Gordish-Dressman Heather , Spurney Christopher
Published: April 2024

Introduction:
Cardiomyopathy is the leading cause of death in Duchenne muscular dystrophy (DMD). Elevated troponin levels are observed in DMD and may vary with disease progression. We studied troponin levels in DMD related to myocardial fibrosis and native T1 measures.

Methods:
This is a prospective, cross-sectional, observational study of 30 DMD subjects measuring native T1 levels and late gadolinium enhancement (LGE) on cardiac MR imaging (CMR) correlated with temporally associated serum troponin I levels. Non-parametric analyses including Spearman correlations and Kruskal-Wallis test were performed between groups. P-values resulting from the pair-wise comparisons were adjusted for multiple comparisons using the Sidak method where appropriate.

Results:
There were 15 DMD subjects with no LGE (age 12±3 yo; EF% 60±5) and troponin I level of 0.05±0.08; 7 DMD subjects with mild LGE (age 17±5 yo, EF% 52±8) and troponin I level of 0.28±0.36; and 8 DMD subjects with moderate to severe LGE (age 16±6 yo; EF% 54±8) and troponin I level of 0.11±0.14. There was a statistically significant positive correlation between troponin I levels and MOLLI septal native T1 values (r2=0.173, p=0.02). Troponin I levels in DMD subjects with mild LGE were significantly increased compared to subjects with no LGE (p=0.02). MOLLI lateral native T1 levels were increased with moderate-severe LGE compared to mild and none (p<0.01), but did not correlate with troponin levels.

Conclusions:
Serum biomarker troponin I levels were increased in DMD subjects with mild LGE and correlated with MOLLI septal native T1 values. Troponin I levels may be a useful minimally invasive outcome marker to monitor myocardial disease progression in DMD cardiomyopathy.
Abstract 16740: Foxo1-Activated Cd36 Transcription Switches Arteriolar Differentiation of Endothelial Cells
Authors: Barnekow Nicholas , Yuan Rong , Moran Patrick , Ren Bin
Published: April 2024

Transcription factor FoxO1 is the most physiologically critical regulator of endothelial stability, essential for vascular homeostasis via its modulation of downstream genes important for angiogenesis and vascular maturation. FoxO1 has been shown to promote expression of vascular endothelial growth factor. Unfortunately, the mechanisms by which FoxO1 specify the different cellular responses and gene targets in endothelial cells (ECs) have not been fully elucidated. The CD36 gene contains FoxO1 binding sites that control its transcription. CD36 is an angiogenic regulator and fatty acid receptor. The LPA/PKD-1 signaling inhibits CD36 transcriptional expression by regulating FoxO1 activities and chromatin remodeling, and mediates transcriptional reprogramming of microvascular ECs (MVECs) for proarteriogenic responses. We thus hypothesize that FoxO1 initiates an arteriolar switch that regulates the development of the microvasculature via regulation of CD36 transcription. To test this hypothesis, we transduced FoxO1 into late passages of primary human MVECs by lentiviral infection and observed that forced expression of FoxO1 significantly increased CD36 mRNA levels by qPCR. FoxO1-induced CD36 expression was attenuated by co-transduction of FCoR, a specific FoxO1 co-repressor. LPA exposure also inhibited FoxO1-induced mRNA expression of CD36. Intriguingly, FoxO1 transduction stimulated the expression of ephrin B2 and Hey2 in primary HUVECs. Our studies thus suggest that FoxO1 does indeed initiate an MVEC arteriolar switch likely via promoting increases in CD36-mediated fatty acid metabolism and VEGF signaling, thus enhancing functional angiogenesis. We have created EC-specific
cd36
null TRAP mice, in which not only is the EC’s CD36 gene deleted, but the EC’s ribosomes are also genetically tagged with GFP, which facilitates isolation of ribosomal mRNA directly in vivo. Further studies are being undertaken to understand the means by which FoxO1 functions at the transcriptional level as a switch to trigger arteriolar differentiation of MVECs.
Abstract 16743: Targeting Renin Activity in Heart Failure: Precision Therapy With Aliskiren Improves Systolic Function and Prolongs Survival in Female Experimental Dilated Cardiomyopathy
Authors: Sullivan Ryan D , Mehta Radhika M , Tripathi Ranjana , Gladysheva Inna P , Reed Guy L
Published: April 2024

Introduction:
Patients with heart failure (HF) are treated according to general therapy guidelines, without precise consideration for the individual’s sex and biomarker profile. Renin activation has been implicated in the pathophysiology of HF progression, but studies of the direct renin inhibitor aliskiren in general HF patients have not shown benefits. Mice with experimental dilated cardiomyopathy (DCM) develop progressive HF with reduced ejection fraction that progresses through all stages (A-D) of human HF. Female DCM mice specifically show an elevation of plasma renin activity with a decline in systolic function, severe HF and enhanced mortality (median survival 103 days). We used aliskiren to determine whether renin activity is critical for HF outcomes.

Methods and Results:
Untreated female DCM mice were compared to female DCM littermate mice given aliskiren (100 mg/kg orally, drinking water) starting at 50 days, Stage B HF (n=20-27/group). When evaluated at 90-100 days, Stage C-D HF, aliskiren suppressed renin activity to normal levels (
P
<0.001) and improved cardiac function (ejection fraction, %: 15±1 vs. 11±1,
P
<0.05; cardiac output, mL/min: 7.5±0.7 vs. 4.6±0.5,
P
<0.01) compared to untreated DCM littermates. Aliskiren also reduced the development of systemic edema (extracellular water, g: 0.36±0.06 vs. 1.25±0.35,
P
<0.0001). Treatment with aliskiren delayed loss of body fat and lean muscle mass consistent with cardiac cachexia and sarcopenia. The strongest predictors of survival were fat mass (

r
p

=0.61,
P
<0.0001), free water (

r
p

=-0.55,
P
<0.0001), and cardiac output (

r
p

=0.53,
P
<0.001). Overall, aliskiren treatment resulted in a 7% improvement in median survival (
P
<0.05).

Conclusion:
In females with experimental DCM, targeted treatment of elevated plasma renin activity with aliskiren slowed the development of edema, decreased cachexia, enhanced systolic function, reduced the progression of HF and prolonged survival. These data suggest that more complete biomarker analysis of HF patients may enhance the precision of HF treatment to better address sex-related and individual differences, in order to improve outcomes.
Abstract 16802: Intermittent Pneumatic Compression for Peripheral Artery Disease and End Stage Renal Disease to Improve Quality of Life and Functional Limitations
Authors: Paz Rios Luis H , Torres Christian , Del Cid Fratti Juan , Ayub Muhammad T , Fuentes Harry E , Al-Ogaili Ahmed , Sleiman Jose , Hart Peter , Tafur Alfonso J
Published: April 2024

Background:
Peripheral artery disease (PAD) is a prevalent condition affecting one in four patients with end stage renal disease (ESRD). Intermittent pneumatic compression (IPC) has proven benefits in PAD. We are conducting a trial testing the utility of IPC in the ESRD population by assessing the improvement in quality of life (QOL), functional limitation and walking performance from PAD-related symptoms. We aim to present our pilot results.

Methods:
Prospective single cohort study undergoing recruitment of outpatients at the hemodialysis (HD) unit of John H. Stroger Hospital. The calculated sample size is 78. PAD is confirmed by ankle-brachial index (ABI) and demographics obtained from interview and chart review. At baseline and post intervention, a Six-minute Walk Test (6MWT), Peripheral Artery Questionnaire (PAQ) and Walking Impairment Questionnaire (WIQ) are administered. The IPC device (Bio Arterial Plus) is used for intervention during HD. We present continuous variables as median (IQR) and categorical variables as percentage. Wilcoxon signed rank test was performed for comparison of results.

Results:
So far, 9 patients have completed intervention for the pilot study, 44% are men, the majority hispanic (66%), with age 48 (41-63) years. At baseline 66% of ABI were abnormal, all due to non-compressible PAD 1.46 (1.20-1.62). All patients have HTN, 44% diabetes, 33% hyperlipidemia and 33% heart failure. The median time of intervention is 70 (60-83) days. There was a significant difference in QOL measured by the WIQ (Fig.1), PAQ physical limitation (p=0.011), and PAQ social limitation (p=0.018). Although there was a trend towards benefit, no statistical difference was found on rest of objective and subjective measured parameters (p>0.05)

Conclusions:
Preliminary, IPC shows to improve many subsets of QOL in patients with ESRD and PAD. Given the small sample, improvement of walking distance remains elusive but with trends towards benefit.
Abstract 16805: Renal Sympathetic Denervation as an Adjunctive Therapy to Radiofrequency Ablation and Cardiac Sympathetic Denervation for Refractory Ventricular Tachycardia
Authors: Liu Kevin C , Do Duc H , Sorg Julie , Buch Eric , Khakpour Houman , Krokhaleva Yuliya , Vaseghi Marmar , Ajijola Olujimi , Fujimura Osamu , Macias Carlos , Pavez Geraldine , Gima Jean , Cote Shelly , Boyle Noel G , Shivkumar Kalyanam , Bradfield Jason
Published: April 2024

Introduction:
The autonomic nervous system plays an important role in initiating and perpetuating ventricular arrhythmias. Neuromodulation procedures aimed at reducing sympathetic outflow to the heart, such as cardiac sympathetic denervation (CSD), can successfully treat many patients with refractory ventricular tachycardia (VT). It is unknown if there is benefit in performing CSD in combination with renal sympathetic denervation (RSD) to treat refractory VT.

Hypothesis:
When used in combination with CSD and catheter ablation, RSD reduces ICD therapy burden in patients with refractory VT.

Methods:
We reviewed adult patients who underwent RSD at UCLA Ronald Reagan Medical Center after presenting with refractory VT despite having received ablation(s) and, in all but one case, CSD. We evaluated the ICD therapy burden 1 month pre-RSD to monthly ICD therapies over the 6 month period post-RSD.

Results:
We performed RSD on 10 patients (mean age=62±10 years,90% male). Nine (90%) had NICM. Mean LVEF was 33±10%. All had prior catheter ablations for VT (median 2 ablations). Of the 9 patients who underwent RSD after CSD, 3 (33%) had both performed during the same hospitalization, of whom 1 died during the hospitalization due to uncontrollable VT. Median follow up was 6.5 months. No further deaths occurred during follow-up. The number of ICD therapies decreased significantly after RSD (total monthly VT episodes pre-RSD was median 11 (IQR 6-23) vs. post-RSD 0.33 (IQR 0-3), p=0.004; monthly ICD shocks pre-RSD was median 5 (IQR 1.5-8) vs. post-RSD 0 (IQR 0-1), p=0.004). Two patients (20%) had complete suppression of VT episodes post-RSD and 6 (60%) had over 75% reduction in VT episodes (Fig. 1).

Conclusions:
We found that RSD was often performed as an adjunctive treatment for patients presenting with refractory VT after catheter ablation and CSD. As hypothesized, RSD in conjunction with CSD significantly reduced the number of VT episodes and ICD shocks over the 6 months following the procedure.
Abstract 16867: Comparison of Ductal Arteriosus Stent and Blalock-Taussig Shunt as Palliation for Neonates With Sole Source Ductal-Dependent Pulmonary Blood Flow: Results From the Congenital Catheterization Research Collaborative
Authors: Bauser Heaton Holly , Qureshi Athar M , Goldstein Bryan H , Glatz Andrew C , Ligon Ronald A , Gartenberg Ari , Aggarwal Varun , McCracken Courtney E , Kelleman Michael S , Petit Christopher J
Published: April 2024

Introduction:
Ductus arteriosus stenting (DAS) is an accepted method for securing pulmonary blood flow in cyanotic neonates. However, in neonates with pulmonary atresia and single source ductal-dependent pulmonary blood flow (SSPBF), DAS remains controversial. Published outcomes in this population are limited. We sought to evaluate outcomes in neonates with SSPBF pts, comparing DAS and surgical Blalock-Taussig shunt (BTS).

Methods:
Neonates with SSPBF who underwent DAS or BTS from four centers of the Congenital Catheterization Research Collaborative from January 2008 to December 2015 were retrospectively reviewed. Peri-procedural complications, reintervention prior to ultimate surgical repair, pulmonary artery (PA) diameter and interval growth were compared using available imaging studies. A propensity score was utilized to compare cohorts adjusted for differences in patient factors.

Results:
Forty patients with DAS and 157 patients with BTS were included. At palliation, the DAS and BTS cohorts had similar age, weight, and expected ultimate physiology. Rates of procedural complications following BTS and DAS were also similar. Following initial palliation, DAS patients were less likely to be treated with inotropes (p <0.01) or diuretics (p = 0.046). Both groups had similar median lengths of hospital stay DAS 19 days (9-38), BTS 13 (10-23), p=0.19 and rates of unplanned reinterventions (17.5% of DAS and 21% in BTS, p= 0.62). Pre-palliation PA diameter was smaller (p=0.02), and PA symmetry was lower (p=0.02) in the DAS cohort. However, by time of definitive repair there was no difference in PA symmetry (0.80 in DAS cohort vs 0.82 in BTS cohort, p=0.64), in PA diameter (Nakata 161mm
2
/m
2
(137-166) in DAS vs 152mm
2
/m2 (94-227) in BTS, p=0.62) or in PA growth (change in Nakata 51mm
2
/m
2
(-21-61) in DAS vs 24mm
2
/m
2
(-28-131) in BTS, p=0.79). Rates of PA plasty and post-repair PA interventions did not differ between the cohorts.

Conclusions:
In neonates with SSPBF, DAS and BTS appear to have equivalent outcomes post-palliation and at time of subsequent surgical repair. Despite concerns about DAS in SSPBF, it appears to be a durable approach with unchanged PA growth compared to BTS.
Abstract 16911: Significant Reduction of Visceral Fat With Doctor-Supervised, Intense Weight Loss Program
Authors: Barnes Jessica , Dembrowski Gerald
Published: April 2024

While effective therapies are available to treat cardiovascular disease (CVD) in the United States, few strategies exist targeting visceral fat (VF) as a means to reduce risk of CVD and other metabolic diseases. Commercial weight loss programs target body weight but provide minimal effect on validated surrogates of CVD risk. VF is a validated direct marker of cardiovascular and metabolic disease risk in both the young and old. The 20Lighter Program (T20LP), a doctor-supervised program combining patent-pending meal plans, nutritional supplementation, and daily oversight is designed to reduce VF, lower risk of disease, and improve health. T20LP employs VF reduction as a clinical indicator of cardiovascular and metabolic disease risk instead of a simple weight loss endpoint. For the first time, we present data collected over the past 3 years from the T20LP including 2200 men and women completing T20LP by Dec 31, 2017. Baseline age (54±9.5), BMI (34.1±6.1), comorbidities, medical history, and prescription medications were typical of metabolic syndrome. From initial baseline to 20 days, 40 days, and 60 days, T20LP participants showed statistically significant and clinically meaningful reductions in % body weight (6.7±0.64, 10.9±0.10, 13.1±0.15) and % visceral fat (14.0±0.24, 20.1±0.31, 25.1±0.43) (Figure 1). Unlike conventional weight loss programs, our results show a significant reduction in VF thereby lowering risk of cardiovascular and metabolic disease. T20LP is a comprehensive lifestyle program capable of complementing pharmacological CVD and metabolic syndrome treatments. Our data suggest a doctor-supervised, structured setting can provide safe and clinically relevant VF reduction in overweight adults and teens at risk of CVD and metabolic disease.
Abstract 16913: Maternal Obesity Impaired Mitochondrial Function of Term Fetal Heart in Sheep
Authors: Wang Qiurong , Odhiambo John F , Rodríguez-González Guadalupe L , Zhu Chaoqun , Smith Ashley , Nathanielsz Peter W , Ford Stephen P , Guo Wei
Published: April 2024

Introduction:
Studies in human and animals suggest that maternal obesity (MO) negatively impacts fetal heart development and cardiac function. Epidemiological studies indicate MO could result in increased incidences of cardiovascular diseases in the offspring. However, the underlying mechanisms are still not well elucidated. Our group has developed and characterized a diet-based sheep model of MO beginning before pregnancy as is common in humans to study the effect of MO on fetal heart function. Previously, we have observed compromised contractility and intracellular calcium in MO fetal cardiomyocytes. Here, we look into the mitochondrial function of the term fetal myocardium.

Hypothesis:
MO impairs fetal heart mitochondrial function and ATP synthesis.

Methods:
From 60 days before and through pregnancy, ewes were fed either 100% of National Research Council (NRC) recommendations (control, n=6) or 150% of NRC’s recommendations (MO, n=7). At 135-day gestation (Term 150 days), the fetal heart was quickly removed under general anesthesia, and cardiomyocytes were isolated and mitochondria were prepared. Mitochondrial biogenesis was measured by using Seahorse extracellular flux analyzer (XF96) on isolated cardiomyocytes and mitochondrial oxidative phosphorylation complex activity were measured with Abcam assay kits. Analysis by Student’s t-test: *p < 0.05.

Results:
The Seahorse mitochondrial biogenesis data suggested that mitochondrial maximal and spare respiration rate were significantly reduced in MO fetal cardiomyocytes. More importantly, MO suppressed mitochondrial ATP production in MO fetal cardiomyocytes. The mitochondrial oxidative phosphorylation was downregulated in MO fetal myocardium. We found that complex I and IV enzyme activity was decreased in MO group. The activity of complex V, ATP synthase subunits, was reduced by 43% in MO fetal heart mitochondria.

Conclusions:
Our results suggest that MO induces stress uterus environment to fetal heart which impairs the mitochondrial function and ATP synthesis, which could be a possible mechanism of maternal obesity-induced cardiac contractile dysfunction.
Abstract 16920: Permanent Reduction of Ryr2 Improves Lv Ejection Fraction in Heart Failure
Authors: Ding Zhiwen , Xu Ran , Yang Chunjie , Wu Jian , Yuan Jie , Wang Shijun , Jiang Guoliang , Li Xuan , Zou Yunzeng
Published: April 2024

Introduction:
Ryanodine receptor type 2 (RyR-2), the main Ca
2+
release channel from sarcoplasmic reticulum in cardiomyocytes, plays an important role in regulation of myocardial contractile function and cardiac hypertrophy.

Hypothesis:
RyR-2 is a target of gene therapy in heart failure.

Methods and Results:
Two CRISPR-Cas9 gRNA targeting RyR-2 were identified: one located on the gene N terminal and the other on the C terminal. Adeno-associated virus was used to express CRISPR-Cas9 to knockdown RyR-2 in two weeks transverse aortic constriction (TAC) model of mice. After one week of administration of the virus, compared with the control, cardiac mass, heart size and fibrosis decreased and the LV ejection fraction increased significantly in the model with CRISPR-Cas9 gRNA on the RyR-2 N terminal, and the other one had a similar result but not significantly.

Conclusions:
Our results hint genome editing with CRISPR-Cas9 disrupts the RyR-2 in vivo with partly restore the function of the heart.
Abstract 16937: Incidence of New Onset Atrial Fibrillation in Lung Cancer Patients
Authors: Marwaha Bharat , Shah Jay , Changal Khalid , Dabbas Maen Al , Waqar Zainulabedin A , Singh Heminder , Taleb Mohammad
Published: April 2024

Introduction:
Atrial fibrillation (Afib) is the most common sustained arrhythmia with prevalence of 5.2 million cases and predicted up to 12.1 million cases in United States by 2030. Recent studies have reported higher incidence of Afib among cancer patients with multiple confounding factors.

Hypothesis:
It is postulated that inflammation is a common denominator for both cancer patients and Afib. Afib may represent inflammatory complication of cancer and correlate with disease burden of lung cancer.

Methods:
Retrospective study. Included were adult (>18 years) newly diagnosed lung cancer patients admitted to 3 Mercy hospitals in the Toledo, Ohio area between May 1, 2013 and December 31st, 2016. Excluded were patients with history of A fib (out of window period), severe MR and MS. N
ew onset of A fib
was defined by new onset paroxysmal or persistent A fib rhythm on 12 lead EKG or rhythm strip diagnosed 6 months before or after the new diagnosis of the lung cancer.

Results:
One hundred sixty newly diagnosed lung cancer patients were included in the study. Of these 160 patients, 37 had new onset A fib (23%, 95% CI: 17% to 30%) and 53 (38%) died within 1 year. Among the A fib patients 4 (11%) had stage 1 cancer, 7 (19%) stage 2, 7 (19%) stage 3 and 17 (46%) stage 4 (2 missing data). Ten of the A fib patients had systolic CHF.

Conclusions:
Our data suggests that about one quarter of newly diagnosed lung cancer patients also have new onset A fib.The incidence of A fib may be higher but is not picked up on routine EKG because of paroxysmal nature. Future studies need to address potential correlation between A fib and pathological type, stage of lung cancer and the role of regular screening for A fib in cancer patients.
Abstract 16978: Use of 2-D Speckle Tracking Strain to Predict Onset of Cardiomyopathy in Chagas Disease
Authors: Miranda Schaeubinger Monica , Win Sithu , Camila Telleria Lola , Tinajeros Freddy , Flores Jorge , Carballo Jimenez Paula , Bern Caryn , Durán Saucedo Ronald Gustavo , Gilman Robert H , Mukherjee Monica
Published: April 2024

Introduction:
Chagas disease is a major cause of morbidity in Latin America where it affects approximately 8 million people, with highest prevalence in Bolivia. An estimated 20-30% of those infected develop Chagas cardiomyopathy (CC) and clinical heart failure. There is currently a lack of reliable predictors of CC, hindering early identification and treatment of patients at highest risk of progression.

Methods:
This prospective observational study was conducted at the Hospital San Juan de Dios in Santa Cruz, Bolivia. Between 2016 and 2018, participants with Chagas disease underwent a focused history and physical exam, 12-lead ECG and echocardiogram at baseline and at 1-year follow-up. Participants were assigned cardiac disease severity stages according to ECG findings and systolic function as done by Okamoto et al. Those classified as stage A or B at baseline were selected from the overall cohort, and considered to have developed cardiomyopathy (stage C or D) by structural abnormalities on their follow-up echo. Echocardiograms were analyzed for peak averaged and regional left ventricular global longitudinal systolic strain (GLS) using TomTec Image-Arena software. Baseline GLS was compared between those who progressed and those who did not using two-sample t-tests.

Results:
Of the 113 participants with stage A or B at baseline, 10 had progressed to stage C or D at follow-up 1 year later. Mean age was similar in the two groups, however those who progressed were more likely to be male (see table). At baseline, mean LVEF was lower and peak GLS was less negative among those who progressed compared to those who did not. These differences were similar at the follow-up visit.

Conclusion:
Mild abnormalities in GLS identify patients with Chagas disease with a higher risk of developing cardiomyopathy within 1 year. Screening for these changes may provide a non-invasive and cost-effective approach to identify patients who could benefit from timely management.
Abstract 11906: Frequency and Characteristics of Coronary Periarteritis: An Intravascular Ultrasound Study
Authors: Tsubouchi Toshiyuki , Ichiryu Hajime , Takai Mizuki , Tochibora Ryota , Ishihara Takeshi , Tateyama Sae , MASUDA YUTO , Endo Susumu , Yoshida Tamami , Hayashi Misayo , Naruse Genki , Yoshida Akihiro , Minatoguchi Shingo , Watanabe Takatomo , Tanaka Toshiki , Takasugi Nobuhiro , Yamada Yoshihisa , Kanamori Hiromitsu , Okura Hiroyuki
Published: April 2024

Objectives:
Recently, several case reports using intravascular ultrasound (IVUS) have demonstrated peri-vascular abnormal mass (PVAM) or tumorous lesions of the coronary artery as coronary periarteritis in patients with IgG4-related disease. The aim of this study was to clarify the frequency and characteristics of PVAM in human coronary arteries.

Methods:
We reviewed 655 coronary vessels in 481 patients who underwent PCI for de novo coronary artery lesions using IVUS from January 1, 2017, to June 30, 2020. PVAM was defined as low echoic abnormal structures with or without high echoic areas that surround the coronary arteries (exterior to media) in a crescentic or circumferential fashion. In addition to standard gray scale IVUS observation, radiofrequency derived tissue characterization of the PVAM was performed to identify tissue characteristics using integrated backscatter IVUS (IB-IVUS).

Results:
PVAM were identified in 4 of 481 patients (0.83%) and 5 of 655 vessels (0.76%), respectively. Mean age was 64 years and 3 were male. Clinical presentation was chronic coronary syndrome in 3 patients and acute coronary syndrome in 1 patient. Mean length of the PVAM was 33 mm (SD 16mm) and the arc was 360°, respectively. The IB-IVUS analysis of the PVAM showed that the lesion had a mixed green, blue and purple color-coded layer (figure), indicating the tissue characteristics similar to those of fibrous plaque and lipid pool.

Conclusions:
Coronary periarteritis was a relatively rare (<1%) finding in patients with coronary artery disease who underwent PCI. Further study with larger sample size is needed to clarify prognostic impact of the coronary periarteritis.
Abstract 11915: Less Aspirin, Less Bleeding for Patients on Chronic Warfarin Anticoagulation for Atrial Fibrillation and/or Venous Thromboembolic Disease
Authors: Schaefer Jordan K , Errickson Josh , Gu Xiaokui , Alexandris-Souphis Constantina , Ali Mona A , Haymart Brian , Kaatz Scott , Kline-rogers Eva M , Kozlowski Jay H , Krol Gregory D , Shah Vinay , Sood Suman L , Froehlich James B , Barnes Geoffrey D
Published: April 2024

Introduction:
For some patients on chronic warfarin anticoagulation for atrial fibrillation and/or venous thromboembolic disease, the addition of aspirin (ASA) may increase bleeding with uncertain therapeutic benefit. Between 2017 and 2018, the six-center Michigan Anticoagulation Quality Improvement Initiative implemented a multi-center quality improvement project to reduce excess aspirin use.

Hypothesis:
We anticipated reductions in overall ASA use and bleeding.

Methods:
Warfarin treated patients taking ASA without a clear indication (eg. coronary artery disease) were identified. Their primary care provider was contacted to advise if ongoing ASA+warfarin was recommended. ASA was discontinued if suggested by their doctor. Data was abstracted by trained abstractors using predefined forms. In December 2019, we evaluated monthly rates of excess ASA use, bleeding, and thrombotic outcomes. Data were analyzed using piecewise linear regression.

Results:
We followed 6,738 patients for a median (interquartile range) of 6.7 months (3.2-19.3 months). Aspirin use declined significantly over the 24 months before our intervention (P<0.001) with an accelerated decline post intervention (p=0.001, Figure 1). Our intervention was associated with a non-significant decline in bleeding (p=0.12), emergency room (ER) visits for bleeding (p=0.35), admissions for bleeding (p=0.97), a significant decline in major bleeding (p=0.029), and no significant change in thrombotic outcomes (p=0.34). Including the decline in ASA use starting 24 months pre-intervention, reducing ASA use resulted in significant declines in any bleeding, major bleeding, and ER visits for bleeding (p=0.021, p=0.001, p=0.038 respectively). There remained no change in thrombotic outcomes (p=0.36).

Conclusions:
Our quality improvement intervention reduced aspirin use. Reductions in aspirin use were associated with reduced bleeding outcomes without increased thrombotic outcomes.
Abstract 11926: Angiotensin-(1-7)/mas Receptor Agonist Protects Hippocampus Neurons In Mouse Model Of Vascular Dementia
Authors: Hoyer-kimura Christina H , Konhilas John P , Mansour Heidi , Polt Robin L , Hay Meredith
Published: April 2024

Decreased brain blood flow, increased inflammation, and increased reactive oxidative species (ROS) are correlated to accelerated progression of both vascular contributions to cognitive impairment and dementia (VCID) and Alzheimer's disease related dementia (ADRD). It has been previously demonstrated that VCID models with blood brain barrier dysfunction exhibit hippocampal neuronal loss and impaired cognitive function.

Our novel synthetic glycosylated Angiotensin-(1-7) derivative (PNA5), has an enhanced half-life and is optimized for better blood-brain-barrier penetration. In our preclinical VCID model, PNA5 treatment inhibits brain ROS production, and reverses cognitive deficits.

We hypothesized that 1) neuronal cell count in the CA1 region of the hippocampus will be decreased in our heart failure (HF) induced VCID mouse model and 2) PNA5 treatment will mitigate neuronal cell loss within the hippocampus and protect cognitive function. VCID was induced in adult male C57BL/6J mice (10-15/group), via HF. Control mice underwent sham surgery. Following 5 weeks post coronary ligation, mice were treated with either 1) saline or 2) 50 micrograms/kg/day PNA5, via daily subcutaneous injection for 21 days. Novel-object recognition was used to measure cognitive function and is represented as a DRatio. VCID-Saline mice displayed cognitive impairment (DRatio mean -0.02, SE
+
0.07) compared to Control-Saline (DRatio 0.57
+
0.1). Cognitive function was rescued by PNA5 treatment (DRatio 50micrograms/kg/day 0.61
+
0.09). Hippocampal neuronal cell loss was determined through analysis of free-floating formalin fixed 16micron cryosection brains, stained with NeuN (ab177487, 1:500) and counted using ImageJ. CA1 Hippocampal regions (-1.6 to -2.0 millimeters from bregma) were imaged at 40x magnification. Data were analyzed by one-way ANOVA. VCID-Saline mice displayed a significant decrease in neurons in the CA1 region (3.35
+
0.11 cell/ pixel linear area) compared to Control-Saline mice (3.94
+
0.12). Mice treated with PNA5 had significantly higher CA1 neuronal cell count (3.87
+
0.17) in comparison to VCID-Saline treated mice. These data suggest that PNA5 protects against VCID cognitive impairment and prevents neuronal cell loss in VCID mouse models.
Abstract 11928: Perm1 Promotes Cardiomyocyte Mitochondrial Biogenesis and Protects Against Hypoxia/Reoxygenation-Induced Damage in Mice
Authors: Cho Yoshitake , Tachibana Shizuko , Lam Kayla , Arita Yoh , Khosrowjerdi Shamim , Zhang Oliver L , Liang Alex , Li Ruixia , Andreyev Aleksander , Murphy Anne N , Ross Robert S
Published: April 2024

Introduction:
Dysregulation of cardiac energy metabolism can result in immature heart development and disrupt the ability of the adult myocardium to adapt to stress, potentially leading to heart failure. In contrast, restoration of abnormal mitochondrial function can have beneficial effects on cardiac dysfunction. Previously, we identified a novel protein termed Perm1 (PGC-1 and ERR induced regulator, muscle 1) that is enriched in skeletal and cardiac muscle and transcriptionally regulated by PGC-1 (Peroxisome proliferator-activated receptor gamma coactivator 1) and ERR (Estrogen-related receptor). The role of Perm1 in the heart is poorly understood and was studied here.

Hypothesis:
We hypothesize that Perm1 plays a crucial role in cardiac metabolism and ischemic injury.

Methods:
To directly study the effect of Perm1 on cardiomyocyte oxidative metabolism, Perm1 or LacZ (control) was expressed in mouse neonatal cardiomyocytes (NCM) using an adenovirus system. We analyzed genes and proteins that play essential roles in cardiac metabolism. NCM were also subjected to hypoxia/reoxygenation (H/R). Finally, to study the mechanism underlying Perm1’s action, we investigated the effect of Perm1 on the activity of ERR and the interaction of Perm1 and PGC-1α.

Results:
Cardiac Perm1 expression was down-regulated in mice with heart failure and human patients with dilated cardiomyopathy. Perm1 selectively regulated PGC-1/ERR targets, such as Ckmt2 and Sirt3. Perm1 interacted with PGC-1α, enhanced activation of PGC-1 and ERRs, and increased recruitment of PGC-1α to the target gene promoters (Ckmt2 and Sirt3), possibly creating a feedforward loop of Perm1 and PGC-1α/ERRs. Perm1 also increased mitochondrial DNA copy number and augmented oxidative capacity in NCM. Moreover, we found that Perm1 reduced cellular damage induced by H/R and mitigated cell death in cardiomyocytes.

Conclusions:
Perm1 promotes mitochondrial biogenesis in mouse cardiomyocytes through PGC-1/ERR and protects cellular damage induced by H/R. Future studies can assess the potential of Perm1 to be used as a novel therapeutic to restore cardiac dysfunction caused by ischemic injury. An NIH grant, R01HL151239, supports this work (To Y. C. and R. S. R.).
Abstract 11934: Lipoprotein(a) Serum Concentrations in Children Are Not Affected by Age, Sex, or Body Mass Index
Authors: Stuerzebecher Paulina , Kiess Wieland , Koerner Antje , Laufs Ulrich
Published: April 2024

Background:
Lipoprotein(a) (Lp(a)) has emerged as an inherited marker of premature atherosclerotic cardiovascular disease (ASCVD). Current ESC guidelines recommend Lp(a) measurement once in the lifetime to identify individuals with high ASCVD risk. Limited data are available on Lp(a) serum concentrations in children.

Methods:
We analyzed 1189 blood samples of 605 healthy children aged 5 to 17 enrolled in the population-based LIFE CHILD (German civilization diseases cohort study). Lp(a) was quantitated using the Cobas/Roche assay.

Results:
The mean Lp(a) of the 605 children was 20.8 ± 1.0 mg/dl (SEM). 74 children (12.2%) showed Lp(a) concentrations between 30 and 50 mg/dl. 78 children (12.8%) exhibited Lp(a) > 50 mg/dl. The mean Lp(a) serum concentrations were distributed evenly between age 5 to 17 years without effects of age on Lp(a) concentrations. Repeated measurements were available in 207 children (2- 6 measurements at least 1 year apart). The measurements were highly reproducible over time (mean percentual difference between repeated measurements of Lp(a) concentration 38.5%, SEM 5%) with a clinically relevant dynamic of Lp(a) values in only 3% of cases. There was no significant correlation between sex and Lp(a) (r=0.09) or body mass index and Lp(a) (r=0.06) whereas higher LDL-cholesterol levels occurred more often in children with elevated Lp(a) (r=0.44, p<0.0001). 6 children with both Lp(a) >50 mg/dl and LDL-cholesterol >150 mg/dl were identified (1% of the 605 children).

Conclusions:
In conclusion, lipoprotein(a) serum concentrations in children between 5 and 17 years are not significantly affected by age, sex, or body weight. These data indicate that Lp(a) may be useful as a marker to identify children at increased lifetime risk for ASCD and suggest that Lp(a) could be used for reverse family screenings. Therefore, Lp(a) may be a valuable addition to screening examinations in children.
Abstract 11936: Macrophage-Specific DNase II Deficiency Stimulates Atherosclerosis in Apolipoprotein E-deficient Mice
Authors: Suto Kumiko , Fukuda Daiju , Sata Masataka
Published: April 2024

Background:
Atherosclerosis is a chronic inflammatory disease of the walls of blood vessels. Macrophage activated by endogenous ligands plays an important role in chronic inflammation of blood vessels. Endogenous DNA fragments derived from vascular cells in the presence of various risk factors attract much attention because endogenous DNA fragments, as well as exogenous DNA fragments induce inflammatory responses through the activation of DNA sensor, including Toll-like receptor 9 (TLR9). We hypothesized that DNase II (DN2) in macrophages degradates incorporated DNA fragments, suppressing pro-inflammatory activation of this cell-type and vascular inflammation. Therefore, we investigated the role of DN2 in macrophages in atherogenesis in apolipoprotein e-deficient (ApoE KO).

Methods and Results:
Macrophage-specific DN2 deleted ApoE KO mice were generated by cross breeding of DN2-flox mice, LysMCre mice, and ApoE KO mice. Mice obtained by cross breeding of DN2-flox mice and ApoE KO mice were used as the control. All mice were fed a western-type diet from 7 weeks of age and received subcutaneous angiotensin II infusion (1000 ng/kg per minute) from 8 weeks of age for 4 weeks. Macrophage-specific DNase II deletion significantly accelerated atherosclerotic lesion development in the aortic arch in ApoE KO mice (P < 0.05), accompanied with the increase in the expression of MMP-9 and TNF-α (P < 0.05, respectively) in the aorta. DN2-deletion significantly promoted the expression of inflammatory molecules such as MCP-1 (P < 0.01) in macrophages in the response to CpG-ODN 1826, a TLR9 agonist, or mitochondrial DNA. mtDNA promoted IkBα degradation in DN2-deficient macrophages, suggesting that NF-kB signal was related to DNA-induced macrophage activation.

Conclusion:
Our results suggested that macrophage-specific DN2 deletion accelerated pro-inflammatory activation of macrophages in the response to DNA fragments, leading to the development of atherogenesis in ApoE KO mice. DN2 may be a potential therapeutic target for atherosclerosis.