bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 16924: Diagnostic Accuracy of Quantification Myocardial Perfusion Ratio Derived From Dynamic CT Perfusion Imaging for Detection of Functionally Significant Stenosis
Authors: Uetani Teruyoshi , Kido Teruhito , Nakao Yasuhisa , Akazawa Yusuke , Kinoshita Masaki , Seike Fumiyasu , Sasaki Yasuhiro , Higashi Haruhiko , Fujii Akira , Aono Jun , Nagai Takayuki , Nishimura Kazuhisa , Inoue Katsuji , Ikeda Shuntaro , Yamaguchi Osamu
Published: April 2024

Introduction:
Quantification perfusion ratio (QPR) is defined as the ratio between myocardial blood flow (MBF) in the stenosis-related territory and MBF in the non-stenosis-related territory derived from stress dynamic CT myocardial perfusion (CTP) imaging.

Hypothesis:
We sought to evaluate whether QPR can be used as a novel non-invasive method for detection of functionally significant coronary artery stenosis compared with fractional flow reserve (FFR).

Methods:
This study was retrospectively included 25 consecutive patients (32 vessels) with coronary artery disease and examined with CT angiography, CTP, coronary angiography, and FFR. QPR and stress MBF results were compared with invasive FFR using a threshold of 0.80.

Results:
The QPRvalues were significantly correlated to FFR values (R=0.865,P <0.0001, Fig 1). The area under the receiver operator curve was larger for QPR (0.937) compared with stress MBF (0.812, Fig 2). The diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of QPR were 93.8%, 86.7%, 100%, 100%, and 89.5%, respectively.

Conclusions:
QPR was feasible and provided high diagnostic value for detecting abnormal FFR in patients with stable coronary artery disease.
Abstract 16931: Alternate UTR Usage Regulates Connexin43 mRNA Translation Limiting Gap Junction Formation During Stress
Authors: Zeitz Michael J , Calhoun Patrick J , Smyth James W
Published: April 2024

Introduction:
Connexin43 (Cx43,
Gja1
) gap junctions enable electrical coupling of cardiomyocytes necessary for heart function. Pathological disruption of Cx43 expression or localization results in the arrhythmias of sudden cardiac death. Investigation of Cx43 gap junction biology has focused on transcription, vesicular trafficking, and post translational modifications. The importance of translational regulation however is highlighted by the recent discovery that Cx43 mRNA undergoes internal translation initiation to yield truncated protein isoforms, including the predominant GJA1-20k isoform capable of regulating gap junction formation. We have found that TGF-β signaling, a hallmark of cardiac stressors including hypertrophy, suppresses GJA1-20k expression to limit gap junction formation. The mechanisms regulating Cx43 mRNA internal translation in response to cellular stress are unknown but are critical in harnessing this biology for therapeutic restoration of electrical coupling in diseased hearts. We hypothesize that altered
Gja1
-5’UTR usage promotes translation of full length Cx43 over internal translation products resulting in reduced gap junction formation during stress.

Methods:
Rapid amplification of cDNA ends was used to identify
Gja1-
5’UTR isoforms following TGF-β exposure or hypoxia, and Western blotting was used to monitor
Gja1
translation. Identified
Gja1
-5’UTR variants were transfected into Cx43 knockout cells to assess translational potential. Luciferase assays assessed potential IRES activity within
Gja1
mRNA in relation to specific 5’UTR isoforms.

Results:
TGF-β or hypoxia significantly increase translation of full length Cx43 over Gja1-20k correlating with an increase in truncated
Gja1
-5’UTRs. Sequenced UTR isoforms map to genome wide transcription start sites and transfection of
Gja1
transcripts with truncated 5’UTRs is sufficient to reduce Gja1-20k translation, phenocopying stress models.

Conclusions:
Alteration of
Gja1
-5’UTR composition represents a powerful mechanism connecting alterations in transcription to gene-specific translational regulation to fine tune intercellular communication during stress.
Abstract 16936: Arterial Pulse Pressure and Outcomes in Patients With Heart Failure and Preserved Ejection Fraction
Authors: Qamer Syed Z , Lam Philip H , Sheriff Helen M , Mohammed Selma , Tsimploulis Apostolos , Faselis Charles , Deedwania Prakash , Fonarow Gregg C , Ahmed Ali
Published: April 2024

Background:
Systolic blood pressure (SBP) is a major determinant of PP. An SBP <120 mmHg is associated with a higher risk of mortality in HFpEF (AHA2016 Abstract 20566). We examined the association of PP with outcomes in patients with HFpEF stratified by SBP of 120 mmHg.

Methods:
Of the 8462 hospitalized patients with HF and EF ≥50% in the Medicare-linked OPTIMIZE-HF registry, 2859 had SBP <120 mmHg (discharge PP: median 48; 1551 had PP <50 and 1308 had PP 50-100 mmHg). Propensity scores for PP <50 mmHg, estimated for each of the 2859 patients, were used to assemble a cohort of 1058 pairs of patients with PP <50 vs 50-100 mmHg, balanced on 57 baseline characteristics. We repeated the above process in the subset of 5603 patients with SBP ≥120 mmHg (PP median 70 mmHg) and in all 8462 patients (PP median 70 mmHg) assembling matched cohorts of 4402 (PP cutoff 70) and 6218 (PP cutoff 60), respectively.

Results:
Among the 2116 matched patients with SBP <120 mmHg, 1-year all-cause mortality occurred in 35% and 33% of patients with PP <50 vs 50-100 mmHg, resp. (HR, 1.09; 95% CI, 0.94-1.26;
Figure
). There was no association with all-cause or HF readmission. HRs (95% CIs) for 1-year mortality in the matched cohorts of SBP ≥120 mmHg (n=4402) and overall (n=6218) were 1.08 (0.96-1.21; p=0185;
Figure
) and 1.21 (1.10-1.32; p<0.001), respectively.

Conclusion:
In hospitalized patients with HFpEF, a lower PP is associated with worse outcomes, but not when stratified by SBP, suggesting that PP has no association with outcomes independent of SBP.
Abstract 16947: Mitochondrial Calcium Uniporter Channel Blockade Ameliorates Sepsis Induced Cardiomyopathy
Authors: Kumar Akshay , Carvalho Edmund , Shanmughapriya Santhanam , Muniswamy Madesh
Published: April 2024

Introduction:
Mitochondria serve as critical Ca
2+
sinks, regulating the duration and magnitude of
c
Ca2+ transients and
c
Ca2+ entry into the mitochondrion. Mitochondrial calcium uniporter (MCU) channel is activated in conditions of inflammation and oxidative stress.MCU and its activity are potential therapeutic targets for cardiac hypertrophy and heart failure.

Hypothesis:
Blunting of mCa2+ uptake can contribute to increased cCa2+ transients associated with excitation-contraction coupling and offer cardio protection following sepsis induced stress.

Methods:
MCU
C96A
KI generated using CRISPR-Cas9
d10
nickase mRNA co-injected with gRNA into wild-type(C57BL6) zygotes and then implanted into pseudo-pregnant female mice.To elucidate mechanistic role of mCa2+ in modulating cardiac contractility and myocardial bioenergetics, adult cardiomyocytes were isolated from mouse model and subjected to hypoxia/re-oxygenation injury.Polymicrobial Sepsis in 6-week-old C57BL/6J mice were created using Cecal ligation and puncture (CLP) and MCU oxidation at 1, 6, 12 and 24 hours post injury was compared with Sham and control mice (n=15). MCU protein quantification was done with western blot, functional assessment of Reactive oxygen species (ROS) by confocal laser microscopy, echocardiography with Vevo2100 imaging system. Mice were pretreated with MCU blocking agent Ru360 1 hr prior to CLP and compared with the control group at 6 hours.

Results:
Cardiomyocytes exposed to hypoxia/re-oxygenation(h/R ) stress exhibited increased MitoSOX red fluorescence.MCU oxidation was ubiquitously induced in all tissues post CLP surgery and was most significant at 6 hrs (Fig 1a). Oxidation of MCU was marked by increase in ROS in tissue sections of small Intestine of CLP versus the Sham group(p<0.001). (Fig 1 b &c). Pretreatment with Ru360 ameliorated MCU oxidation at 6 hours post CLP injury. MCUC96AKI had significantly decreased ejection fraction and fractional shortening compared to the wild type mice. Further the survival in MCU
C96A
KI was significantly better than the WT or MCU KO mice ( p<0.05).

Conclusions:
Inhibition of mitochondrial calcium uniporter is a potential therapeutic target and protects from sepsis induced cardiomyopathy by mitigating mitophagy.
Abstract 16965: Microvesicles Rescue Cardiomyocytes From Doxorubicin Injury in a Patient Specific Model of Anthracycline Induced Cardiomyopathy
Authors: O’Brien Connor G , Shi Liye , Santoso Michelle R , Jung Ji-Hye , Vaskova Evgeniya , Ikeda Gentaro , Ozen Mehmet O , Demirci Utkan , Yang Phillip C
Published: April 2024

Introduction:
Anthracyclines are highly effective chemotherapeutic agents associated with cardiac toxicity. Anthracycline induced cardiomyopathy (AIC) carries a reported mortality rate in excess of 20% at four years on medical therapy. Effective therapies for AIC have not been established. The Stem Cell Injection for Cancer Survivors (SeNeCA) trial is examining the role of allogenic mesenchymal stem cell (MSC) therapy in treating AIC. To understand the mechanism and predict the efficacy of MSCs in myocardial recovery, we evaluated the restorative effects of MSCs following doxorubicin (dox) administration
in vitro
, employing iPSC- derived cardiomyocytes (iCM) generated from trial patients.

Hypothesis:
MSCs will rescue AIC patient-specific iCM from dox injury.

Methods and Results:
We generated three AIC patient-specific iPSC lines from SeNeCA patients.
In vitro
dox sensitivity was shown to be comparable to published values for AIC patient iCM. iCM were then cultured in 1μM dox for 24hrs and assessed for viability and apoptosis 72- hours post-injury by annexin-PI, ApoLive Glo, and tetrazolium (MTT) assay. MSC efficacy was assessed using co-culture. 2.5 x 10^5 iCM were plated and co-cultured with 2.5 x 10^5 MSC using a 1μm pore trans-well system. Compared to monoculture, MSC co-culture improved post- doxorubicin iCM viability significantly (50.0±4.0%* vs 35.7±0.8%, *p-value< 0.005) by MTT and reduced apoptosis significantly (40.4±2.9%* vs 48.6±0.8%, *p-value<0.01). Reactive oxygen species (ROS) production was also reduced (25.5%* vs 16%) by CellRox. MSC-derived microvesicles (MV) were assessed as potential effector molecules. MV demonstrated a dose- dependent effect with statistically significant improvement in viability achieved at a dose of ~500 MV/cell (44.5±4.4%* vs. 34.9±4.4%, *p-value<0.06) by MTT. Results were corroborated by ApoLive Glo and annexin PI showing significantly reduced apoptosis and increased viability.

Conclusion:
Allogeneic MSCs can attenuate apoptosis and ROS production following doxorubicin injury in patient-specific iCM. This effect is largely mediated via MV. Our findings will be validated by the SeNeCA trial demonstrating proof-of-concept in
in vitro
clinical trials employing iPSC-derivatives.
Abstract 16973: Thrombotic and Bleeding Outcomes of Pregnancy in Women With a Fontan Circulation
Authors: Girnius Andrea K , Zentner Dominica , Ladouceur Magalie , Canobbio Mary , Aboulhosn Jamil , Valente Anne Marie , Book Wendy , Bradley Elisa , Grewal Jasmine , Partington Sara , Venuti Morgan , Buber Yonatan , Mulder Barbara J , Bouma Berto , Ollberding Nicholas , Mirani Amita , Faust Michelle , Veldtman Gruschen
Published: April 2024

Introduction:
Patients with a Fontan circulation are at increased risk of bleeding as well as thrombosis. Current strategies to mitigate this risk during pregnancy are not well studied.

Hypothesis: We hypothesize pregnant women with a Fontan circulation would have a higher risk of bleeding at baseline and anticoagulation (AC) therapy would increase this risk compared to antiplatelet (AP) therapy.

Methods:
This is an international multicenter retrospective cohort study of women with a history of Fontan palliation and pregnancy (2007-2017). Outcomes analyzed include AC/AP therapy and bleeding and thrombosis complications for each pregnancy.

Results:
There were 97 pregnancies in 74 women (26.9
+/-
4.6 years old, 25(25.5%) ending in miscarriage). Median gestational age at delivery was 35 weeks (IQR 7 weeks), with a birth weight of 2140grams (IQR 898). Bleeding complication occurred in 33 (35.1%) of pregnancies; the majority were from postpartum hemorrhage/PPH (30(88.2%)). 7(18%) patients required transfusion therapy. Of the 33 pregnancies with bleeding complications, 5 (15.2%) were on combination AC/AP therapy, 17 (50%) on isolated AC and 10 (29.4%) on isolated AP therapy. Only 1 patient with a bleeding event was on no therapy. In the non-bleeding complication cohort (n=37), 6 (16.2%) were on AC/AP therapy, 14 (37.8%) on isolated AC and 14 (37.8%) on isolated AP therapy. There were 3(8.1%) who received neither AC nor AP therapy. Thrombosis occurred in 2 patients (intracardiac n=1, thromboembolic event n=1), both of which were on combination AC/AP therapy.

Conclusions:
Bleeding risk is high in pregnant women with Fontan circulation, especially during the post-partum period. In this analysis, bleeding risk in those on therapy was higher than what is reported in non-Fontan populations receiving similar therapy. Further study is necessary to discern the relative contribution of anti-thrombotic and antiplatelet strategies to this risk. Thrombosis risk seems to have been effectively minimized with the above antithrombotic strategies.
Abstract 16980: Defining the Arrhythmia Burden in Adults With Repaired Coarctation of the Aorta
Authors: Lastinger Lauren T , Cavus Omer , Hassen Lauren , Bradley Elisa
Published: April 2024

Introduction:
Ventricular and atrial arrhythmias have been shown to correlate with the risk of sudden cardiac death (SCD) in adult congenital heart disease (ACHD). Patients with repaired coarctation of the aorta (CoA) remain one of the highest risk ACHD populations for late SCD. However, the etiology of SCD is poorly understood in this population.

Hypothesis:
We hypothesize that adults with repaired CoA have an increased prevalence of atrial and ventricular arrhythmia.

Methods:
We identified 165 adults with repaired CoA (39±11years old, 45% women) and retrospectively analyzed all cardiac rhythm testing (2008-2018). The prevalence of atrial fibrillation (AF), atrial flutter (AFL), supraventricular tachycardia (SVT) and non-sustained ventricular tachycardia (NSVT) were analyzed and compared to prevalence in the general (non-repaired CoA) population.

Results:
Ventricular and atrial arrhythmia were found to be more common in adults with repaired CoA. The odds of NSVT occurring were 2.4 (95% CI: 1.5-3.8). Atrial arrhythmia risk varied by type with the odds of atrial arrhythmia in the CoA group ranging from 4.4 to 129 times the risk of the general population (See Figure).

Conclusions:
In this relatively young cohort of adults with repaired CoA, the incidence of ventricular and atrial arrhythmia was significantly higher than the general population. This data indicates that further study of arrhythmogenic substrate for SCD in repaired CoA is important.
Abstract 16989: Use of Screening Echocardiography to Improve Healthcare in Underserved Areas of Brazil: Data From the PROVAR+ Study
Authors: Diamantino Adriana C , Nunes Maria Carmo P , Sable Craig , Nascimento Bruno R , Lima Emily M , Martins Larissa N , Colossimo Enrico A , Diamantino Tatiana C , Rezende Breno D , Rios João Pedro P , Beaton Andrea Z , Ribeiro Antonio Luiz P
Published: April 2024

Introduction:
Access to public health care is limited in Brazil, especially in remote areas and many patients remain on long waiting lists for echocardiography (echo). Advances in handheld echo and telemedicine provide an opportunity for integration of screening for cardiovascular disease into the existing primary care system. This may improve early detection of heart disease (HD) and guide prioritization of referrals. We aimed to test the accuracy of screening echo to identify significant HD in this setting.

Methods:
Patients on waiting lists for the echos were eligible and answered a standardized clinical questionnaire. All subjects underwent focused 7-view screening echo (GE VSCAN), acquired by non-physicians in primary care centers and interpreted remotely by experts through cloud-storage and telemedicine. All patients underwent standard echo (GE Vivid Q), performed by an expert, blinded for the screening echo images and diagnoses. Significant HD was defined as any ventricular dysfunction, moderate to severe valve disease, moderate to severe left ventricle hypertrophy, aortic root dilatation or congenital heart disease. Statistical analysis was performed using classification and regression tree analysis based on 70% of the sample for training and 30% for test.

Results:
Over 9 months we evaluated 569 patients. Median age was 58.7 years, 61.4% were females, 71.6% had hypertension, 22.9% diabetes, 16.3% Chagas disease, 9.3% coronary disease, 4.8% valve disease. The most frequent symptoms were chest pain, dyspnea and palpitations, isolated or in combination, and 29.5% were asymptomatic. The presence of symptoms was not a good predictor for abnormal echo findings. Significant HD was observed in 147 (25.8%) patients on the standard echo. The model utilizing clinical features alone didn′t show a good accuracy on detecting significant HD. The screening echo alone had a negative predictive value of 0.94, with an overall accuracy of 78%. The integration of the screening echo variables with clinical features on the decision tree generated an accuracy of 82.4%, using the variables with statistical significance (Chagas disease, valve disease, coronary disease, body mass index, gender and age).

Conclusions:
Integration of screening echo into primary care is feasible in Brazil and should ensure that patients with higher needs have priority access to standard echocardiography and referrals. The burden of HD observed and the accuracy of screening echo performed by non-physicians suggests this tool may help deliver health care to underserved areas.
Abstract 16995: Inhibition of lncRNA MAAT Contributes to Multiple Types of Muscle Atrophy
Authors: Li Jin , Yang Tingting , Pan Wen , Xiao Junjie
Published: April 2024

Background:
Skeletal muscle atrophy is the consequence of many diseases, such as denervation, long-term inactivity, excessive fasting, ageing, and heart failure. Recently, increasing studies have shown that long noncoding RNAs (lncRNAs) play an important role in myogenesis and adult skeletal muscle regeneration. However, if lncRNAs are responsible for muscle atrophy remains largely unclear.

Hypothesis:
We aimed to select and investigate the role of lncRNAs in muscle atrophy.

Methods and Results:
LncRNA arrays indicated that several lncRNA transcripts were changed during denervation-induced muscle atrophy in mice. After detecting the expression of lncRNAs in multiple types of muscle atrophy
in vivo
(denervation, Angiotensin II and fasting induced muscle atrophy) and
in vitro
(Angiotensin II, H
2
O
2
and TNFα induced muscle atrophy) by qRT-PCRs, we identified that MAAT (Muscle Atrophy-Associated Transcript) was down-regulated in multiple types of muscle atrophy. Then lentivirus of shRNA and overexpression of MAAT were further used to study the role of MAAT in muscle atrophy
in vitro
and
in vivo
. We found that knockdown of MAAT promoted muscle atrophy, whereas upregulating MAAT prevented multiple types of muscle atrophy. Mechanistically, we found that MAAT negatively regulated the transcription of microRNA-29b through SOX6, and that MAAT influenced the expression of neighbor gene-MBNL by a cis-regulatory module.

Conclusions:
Inhibition of LncRNA MAAT contributes to muscle atrophy by increasing miR-29b and repressing MBNL. Overexpressing MAAT might be a novel approach to counteract muscle atrophy.
Abstract 16999: Effect of Positional Echocardiogram on Right Sided Hemodynamics in Pectus Excavatum Patients vs. Healthy Adults
Authors: Pulivarthi Venkata Siva Krishna , Jaroszewski Dawn , Arsanjani Reza , Mookadam Farouk
Published: April 2024

Introduction:
Pectus excavatum (PE) is the most common anterior chest wall deformity with dorsal deviation into the thoracic cavity. Depending on the severity, PE can cause minor cosmetic problem to significant cardiac compression in severe cases. This compression most frequently affects right heart chambers causing symptoms such as dyspnea, palpitations, fatigue, exercise intolerance, and difficulty with keeping up with peers. Previously, we reported the change in these symptoms with positon associated with change in right heart hemodynamics. Further, we are comparing the changes in right heart hemodynamics with position in pectus patients to normal healthy adults.

Methods:
A prospective cohort of 40 pectus excavatum patients (mean Haller index: 5.4±2) undergoing evaluation at Mayo clinic underwent 2-D transthoracic echo (TTE) with Doppler assessment of Right Ventricular Outflow Tract (RVOT) Velocity Time Integral (VTI). A cohort of 8 healthy adults without chest wall abnormality who had clinically indicated echocardiogram was used as control (Table). Additional assessment of the RVOT VTI was performed in sitting position in either group. A two-sample t-test was performed to assess significance between cohorts.

Results:
There is a significant difference in RVOT VTI between case and control cohorts in both supine and sitting positions (p=0.03 & p=0.001 respectively). Also, there is a significant decrease in RVOT VTI from supine to sitting position in PE patients compared to healthy adults (Table).

Conclusion:
This is the 1
st
prospective cohort study in PE patients vs healthy adults showing the feasibility and utility of dynamic echocardiography in assessing the right ventricular hemodynamics. This study demonstrates a significant decrease in right sided hemodynamic changes with change in position in patients with PE which might explain their symptoms.
Abstract 17003: Impact of Ex-Vivo Lung Perfusion on T Regulatory Cells and Monocytes in Bronchoalveolar Lavage and Peripheral Blood
Authors: Chacon Lourdes I , Loor Gabriel T , Daoud Daoud T , Alnajar Ahmed T , Sampaio Luiz C , Taylor Doris A
Published: April 2024

Background:
Availability of donor lungs suitable for transplant falls short of current demand and results in long waiting times. More than 80% of donor lungs are potentially injured and therefore not considered suitable for transplantation. Ex-Vivo Lung Perfusion (EVLP) offers the opportunity to objectively assess and recondition organs unsuitable for immediate transplant. However, the biological mechanisms of EVLP are not well understood. The objective of this study was to investigate the Bronchoalveolar Lavage (BAL) and peripheral blood (PB) inflammatory cell profile in patients who had EVLP. We hypothesized that EVLP is related to a differential expression of monocytes in BAL and PB as compared to patients who did not receive EVLP.

Methods:
BAL was collected and analyzed via flow cytometry at baseline (before transplant) and 6 h after transplant. PB was collected and analyzed at baseline, 6 h, 24 h, 48 h, and 72 h after transplant from consented participants (EVLP and non-EVLP, n=5 each). Statistical difference between groups were determined using t-test and nonparametric tests. A p-value <0.05 was considered significant.

Results:
In the donor lung prior to transplant, classical monocytes (CD14+CD16-) were significantly higher in BAL at baseline (77.48±4.64 vs. 32.30±23.12, p=0.04) in the EVLP group when compared to non-EVLP group. In the recipients at 6 h after transplant, the EVLP group had a significant increase in T regulatory cells (Treg) (CD4+CD25+CD127dim) in BAL (4.08±1.2 vs. 18.00±6.61, p=0.05) and classical monocytes (CD14+CD16-) in PB (66.2 vs. 90.8, p=0.04) when compared to baseline. Additionally, the EVLP group had significantly higher M2 monocytes (CD14+CD80-CD163+) (86.97±7.21 vs. 62.85±3.15, p=0.03) in PB at 6 h after transplant when compared to non-EVLP group.

Conclusion:
EVLP causes a significant change in monocytes, their subpopulations and regulatory T cells in the donor and recipient.
Abstract 11988: Trends and Variation of Red Blood Cell Transfusion in Coronary Artery Bypass Grafting in China, 2014-2019
Authors: Zhang Danwei , Qu Jianyu , Zheng Zhe ,   Chinese Cardiac Surgery Registry Collaborative Group
Published: April 2024

Introduction:
Red blood cell (RBC) transfusion is common for cardiac surgeries, but safety problems are of concern, and some countries have taken initiatives to limit RBC use. The trends and variation of RBC transfusion in coronary artery bypass grafting (CABG) across China remain unknown, which is essential for quality control on reducing unnecessary transfusion.

Hypothesis:
To assess recent trends of perioperative RBC transfusion and variation across hospitals and surgeons among patients undergoing elective isolated CABG.

Methods:
We used data from a national CABG registry with detailed clinical information of patients undergoing elective isolated CABG between 2014 and 2019. The overall and hospital-level rates of perioperative RBC transfusion were described and compared across study years. Hierarchical models were used to make risk-adjusted between-hospital comparison, and to quantify variations derived from hospitals and surgeons.

Results:
A total of 47554 CABG patients from 72 hospitals were included, with a mean age of 62.7 (standard deviation [SD]: 8.8) years and 75.4% were male. The overall perioperative RBC transfusion rate was 43.9% during the study period. A remarkable decline of RBC transfusion from 51.6% in 2014 to 39.8% in 2019 (P for trend<0.001) was observed, along with the mean hospital-level transfusion rate declined from 56.6% (SD: 26.9%) to 48.1% (SD: 26.1%), and minimal amounts (1-2 units) of RBC declined from 21.9% (SD: 16.3%) to 18.3% (SD: 13.1%). Hospital-level intraoperative transfusion had a similar decreasing amplitude (from 34.8% to 28.7%) with postoperative transfusion (from 38.7% to 32.4%), and the Pearson correlation coefficient was 0.32 (P<0.01). After risk adjustment of patient characteristics, the median odds ratio (MOR) of perioperative RBC transfusion between hospitals was 3.9 in 2014 and reduced to 3.2 in 2019. Furtherly, the relative proportion of variation hospitals explained decreased from 88.0% to 76.0% while increased for surgeons from 12.0% to 24.0%.

Conclusions:
There is a considerable decline of perioperative RBC transfusion in CABG patients in China during last few years, with notable reductions in between-hospital variation. However, strategies to narrow between-surgeon variation are required.
Abstract 12326: Obesity Increases Heart Failure Incidence and Mortality:Observational and Mendelian Randomisation Studies Totalling Over 1 Million Individuals
Authors: Benn Marianne , Marott Sarah C , Tybjaerg-hansen Anne , Nordestgaard Borge G
Published: April 2024

Introduction:
Whether high body mass index (BMI) causally influences development and prognosis of heart failure has implications for clinical practice.

Hypothesis:
We tested the hypotheses that high BMI causally influences heart failure incidence and mortality.

Methods:
Using observational and Mendelian randomization causal, genetic analyses, we studied 106,121 individuals from the Copenhagen General Population Study, 18,407 from the Copenhagen City Heart Study, and 977,323 from publicly available databases.

Results:
In observational analyses in the Copenhagen studies with 10 years of median follow-up, multivariable adjusted hazard ratios per 1 kg/m
2
increment of BMI were 1.06 (95% confidence interval: 1.05-1.07; p<0.001; n=124,528; events=6,589) for heart failure incidence, 1.04 (1.03-1.06; p<0.001; n=124,528; events=1,237) for heart failure mortality, and 1.01 (1.00-1.01; p<0.001; n=124,528; events=24,144) for all-cause mortality. In genetic analyses in the Copenhagen studies, the age and sex adjusted causal risk ratios per 1 kg/m
2
increment of BMI were 1.19 (1.05-1.36; p=0.008; n=118,200; events=6,541) for heart failure incidence, 1.27 (0.82-1.98; p=0.28; n=118,200; events=889) for heart failure mortality, and 1.11 (1.02-1.22; p=0.022; n=118,200; events=16,814) for all-cause mortality. Finally, combining genetic data from the Copenhagen studies, the Genetic Investigation of ANthropometric Traits (GIANT), the Heart Failure Molecular Epidemiology for Therapeutic Targets (HERMES), and the UK Biobank, the unadjusted causal risk ratios per 1 kg/m
2
increment of BMI were 1.39 (1.27-1.52; p<0.001; n=1,095,523; events=53,850) for heart failure incidence, 1.18 (1.00-1.38; p=0.05; n=576,853; events=2,373) for heart failure mortality, and 1.02 (1.00-1.04; p=0.03; n=576,853; events=44,734) for all-cause mortality.

Conclusions:
High body mass index causally increases the risk of both heart failure incidence and mortality. Obesity should be recognised as a causal factor for development of heart failure, heart failure mortality, and all-cause mortality in treatment guidelines.
Abstract 12348: Urine Albumin to Creatinine Ratio on Admission Predicts Early Rehospitalization in Patients With Acute Decompensated Heart Failure
Authors: Matsumoto Yuki , Asakura Masanori , Min Kyung-Duk , Sunayama Isamu , Azuma Kouhei , Nishimura Koichi , Naito Yoshiro , Goda Akiko , Ishihara Masaharu
Published: April 2024

Introduction:
Detecting high-risk patients for early rehospitalization is crucial in heart failure patient care. An association of albuminuria with cardiovascular events is well known. However, its predictive impact on rehospitalization for acute decompensated heart failure (ADHF) remains unknown.

Hypothesis:
The aim of this study was to clarify the utility of urine albumin to creatinine ratio (UACR) in ADHF patients.

Methods:
Two hundred and sixty consecutive patients who were admitted due to ADHF between December 2017 and April 2019 were enrolled. Further investigated were 140 patients from whom UACR was measured with spot urine samples on admission. The association between UACR and rehospitalization due to HF during 1 year after discharge was evaluated.

Results:
The mean age of 140 participants was 77.6 years and 55% were men. Only 18% (n=25) of patients presented with normoalbuminuria (UACR<:30mg/g·creatinine), whereas 59% (n=83) and 23% (n=32) showed microalbuminuria (UACR30-300mg/g·creatinine) and macroalbuminuria (UACR>:300 mg/g·creatinine), respectively. The level of UACR on admission was correlated with the risk of subsequent rehospitalization due to HF (p=0.017). The Receiver operating characteristic analysis indicated that the best cut-off values for the UACR and B-type natriuretic peptide (BNP) levels to predict ADHF rehospitalization were 50 mg/g·creatinine and 824 pg/ml, respectively. When the patients were divided into four groups using both cut-off values, the individual predictive impacts of UACR and BNP on rehospitalization were comparable. In the patients with both elevated UACR and BNP levels, the rehospitalization rate due to HF was higher than those with elevated BNP levels alone (p=0.041).

Conclusions:
The UACR is useful, when combined with BNP levels, to predict the risk for HF rehospitalization.
Abstract 12350: Modulation of Fibrosis Arrhythmogenicity Improves the Accuracy of Patient-Specific Computational Modeling in Persistent Atrial Fibrillation
Authors: Macheret Fima , Bifulco Savannah F , Scott Griffin D , Kwan Kirsten T , Akoum Nazem W , Boyle Patrick M
Published: April 2024

Introduction:
Computational models incorporating left atrial (LA) anatomy and fibrosis from MRI can identify post-ablation recurrence mechanisms in persistent atrial fibrillation (PsAF) patients. However, model accuracy is limited since fibrosis arrhythmogenicity (FA) is simulated identically across all models.

Hypothesis:
In each model, there exists an optimal FA level such that pre- and post-ablation simulation behaviors match the corresponding patient’s clinical outcome.

Methods:
50 LA models were constructed from pre- and ≥90 days post-ablation late gadolinium enhanced MRI in 25 PsAF patients. Virtual pacing was used to probe for arrhythmia inducibility due to AF-like reentrant drivers (RD; i.e., rotors) or atrial flutter (AFL)-like macro-reentry (MR). FA variability was modeled in all patients by altering conduction velocity (CV) ±10% vs baseline (71.5cm/s). No recurrence (NR) was defined as ≥2 years arrhythmia-free. Pre-ablation, accuracy was assessed by confirming ≥1 RD was inducible; post-ablation models for patients with AF, AFL, or NR were screened for RD, MR, or non-inducibility, respectively.

Results:
At baseline FA, 26/50 (52%) models had simulations matching clinical outcome. When simulations with modulated FA were added, 36/50 (72%) models had simulations matching clinical outcome (Fig A; two-sample proportion t-test, p=0.034). FA modulation improved accuracy in three scenarios: eliminating non-inducible pre-ablation models; unmasking RD inducibility in post-ablation models for patients with AF recurrence; and abolishing inducibility in post-ablation models for NR patients (activation maps shown in Figs B-D, respectively).

Conclusion:
Modulation of FA in computational models of PsAF improved correlation between simulation behavior and clinical outcomes. This suggests that if FA can be quantified pre-ablation (e.g., via biomarker assay), it could create a new paradigm for model personalization with improved accuracy.
Abstract 12351: Perioperative Interventions for Prevention of Postoperative Atrial Fibrillation After Cardiac Surgery: A Systematic Review and Network Meta-Analysis
Authors: Li Zhongchen , Zeng Zhiwei , Yuan Shuo , Zhang Xingyi , Zheng Zhe
Published: April 2024

Background:
Postoperative atrial fibrillation (POAF) is the most common complication of cardiac surgery, which increases the risk of stroke and death, the length of hospital stays, and costs. Guidelines recommendations on the use of β-blockers (BBs) have only a modest influence on overall rates of POAF. The key clinical outcomes such as stroke and death have not been improved. The best approach to prophylaxis remains obscure.

Method:
We used Bayesian network meta-analysis to synthesize evidences from randomized controlled trials (RCTs) that compared interventions for POAF prophylaxis. The primary outcomes were incidence of POAF hypotension and bradycardia.

Results:
We included 262 RCTs with 52636 participants (age > 18, undergoing CABG, valvular or combined surgery), in which 14 different interventions were investigated. For the incidence of POAF, sotalol, amiodarone, BBs, posterior pericardiotomy, atrial pacing, magnesium, polyunsaturated fatty acids, colchicine, glucocorticoid and statin had positive results compared to placebo with statistical significance. The best three therapeutics were sotalol (OR 0.29, 95% CI 0.21-0.41; probability of being best 84.6%), amiodarone (OR 0.39, 95% CI 0.31-0.48) and BBs (OR 0.39, 95% CI 0.31-0.49). For safety, BBs (OR 4.09, 95% CI 2.10-7.96), magnesium (OR 2.51, 95% CI 1.09-5.76) and sotalol (OR 2.07, 95% CI 1.06-4.05) were associated with higher incidence of hypotension. Sotalol (OR 2.80, 95% CI 1.66-4.74) and amiodarone (OR 2.27, 95% CI 1.66-3.10) were associated with higher incidence of bradycardia. For secondary outcomes, no significant effect on all-cause or cardiovascular mortality was observed. Amiodarone was the only intervention that reduced stroke rate (OR 0.57, 95% CI 0.34-0.96).

Conclusions:
Sotalol appeared to be superior in efficiency compared with others. BBs do not work as well as we expected with the highest incidence of hypotension.Further studies are required to define the better interventions
Abstract 12355: An Engineered High-Affinity ACE2 Peptide Therapeutically Alleviates Lung Vascular Endothelial Injury and Mortality Induced by Distinct SARS-CoV-2 Variants
Authors: Zhang Lianghui , Gugliuzza1 Anthony F , Procko Erik , Rehman Jalees , Malik Asrar B
Published: April 2024

Introduction:
Vaccine hesitancy and the continuous emergence of SARS-CoV-2 variants of concern that partially escape vaccine-induced immune responses highlight the urgent need for the development of effective therapeutics for COVID-19 patients.

Hypothesis:
The Engineered high-affinity ACE2 peptide has a therapeutic effect for SARS-CoV-2 and its variant-induced acute lung vascular injury.

Methods:
K18-hACE2 transgenic mice were inoculated with SARS-CoV-2 WA-1/2020 or P.1 variant of concerns to induce acute lung injury. The sACE2
2
.v2.4-IgG1 was injected once a day for consecutively 7 days starting from 12 hours at 10 mg/kg/day or 24 hours at 15 mg/kg/day post-SARS-CoV-2 inoculation.

Results:
We demonstrated that the higher binding affinity of sACE2
2
.v2.4-IgG1 to S proteins of the original SARS-CoV-2 WA-1/2020 isolate and the B.1.1.7 (Alpha, UK isolate), B.1.351 (Beta, South Africa isolate), P.1 (Gamma, Brazil isolate), and B.1.617.2 (Delta, India isolate) SARS-CoV-2 variants of concern compared to wild-type soluble ACE2. Using humanized K18-hACE2 mice, we found that both SARS-CoV-2 isolate WA-1/2020 and the P.1 variant of concern induced severe acute lung endothelial injury, which resulted in the severe transvascular leak, lung edema, and death. The P.1 variant induced severe lung vascular leak and death at an earlier time point at Day 5 compared to WA-1 at Day 7, consistent with increased viral entry and replication. Treatment with sACE2
2
.v2.4-IgG1 decoy peptide could be initiated as late as 24h after inoculation with a lethal dose of the SARS-CoV-2 WA-1/2020 isolate and profoundly reduces lung vascular injury and mortality. For the P.1 variant of concern, ACE2
2
.v2.4-IgG1 decoy peptide markedly improved survival and reduced lung vascular injury if administered early at 12 hours post-inoculation.

Conclusion:
sACE2
2
.v2.4-IgG1 has an exceptional therapeutic efficacy to SARS-CoV-2 WA-1/2020 and variant P.1 -induced acute lung vascular injury.
Abstract 12370: Prognostic Value of Inflammatory Markers in Recurrent Pericarditis
Authors: Kumar Ashwin K , Yesilyaprak Abdullah , Furqan Muhammad M , Verma Beni , jain vardhmaan , Gad Mohamed , Agrawal Ankit , Montane Bryce , Jellis Christine , Cremer Paul , Klein Allan L
Published: April 2024

Background:
Expert guidelines recommended the use of inflammatory markers for the confirmatory diagnosis of recurrent pericarditis (RP), however the prognostic role in management is unknown. Inflammatory marker levels in RP fluctuate, therefore measurement during flare is paramount. We attempt to assess the prognostic value of inflammatory markers (ESR, hs-CRP) taken during active flare in idiopathic/viral RP.

Methods:
We retrospectively reviewed 130 patients with established RP from 2015 to 2019 with inflammatory markers during flare. RP was diagnosed if two of these features were present; pleuritic chest pain, EKG changes, rub, and effusion. Active flare was defined as pleuritic chest pain with raised inflammatory markers. Clinical improvement (CI) and remission (CR) were assessed. CI was defined as symptom improvement on dual anti-inflammatory therapy. CR was established with symptom resolution and cessation of therapy.

Results:
Mean age was 46 ± 16, 57% were female, and a median number of recurrences was 3. The median follow-up time was 633 days, and median time to first recurrence was 263 days. Patients with lower hs-CRP <10 mg/L were more likely to have CI as compared to the higher hs-CRP ≥10 mg/L group (79% vs 42%, p=0.012). Also, patients in the lower hs-CRP group showed a higher tendency to achieve CR (43% vs 20%, p = 0.081). ESR was statistically insignificant for the outcomes. The median time to CI in the low hs-CRP group was less compared to the high hs-CRP group (11 vs. 32 months). Majority of high hs-CRP patients did not achieve CR. The probability of CI and CR among low hs-CRP is higher as compared to high hs-CRP (log-rank p=0.001; log-rank p=0.034) [Figure 1].

Conclusion:
Patients who had higher hs-CRP were less likely and required more time to achieve CI and CR as compared to patients with lower hs-CRP. This highlights the prognostic significance of hs-CRP that may assist management of RP even without a concurrent ESR level.

Figure 1:
Kaplan-Meier Analysis of CI and CR
Abstract 12374: Physiologic Changes of COVID-19 Infection Detected by Cardiac Implantable Electronic Device Data
Authors: Reading Turchioe Meghan , Ahmed Rezwan , Masterson Creber Ruth M , Axsom Kelly , Horn Evelyn , Sayer Gabriel T , Uriel Nir , Slotwiner David J
Published: April 2024

Background:
The trajectory of cardiac physiology throughout a COVID-19 infection remains poorly described. This study aimed to characterize physiologic changes associated with acute COVID-19 infection among patients with cardiac implantable electronic devices (CIEDs).

Methods:
The study population included 286 patients with a Boston Scientific CIED across a large health system. CIED sensor data from March 2020 - February 2021 were linked to clinical data from electronic health records. Three cohorts were created: COVID-positive (n=20), COVID-negative (n=166), and an untested control (n=100) to account for testing bias as institutional protocols only allowed symptomatic patients to be tested in the early months of the study. The magnitude of sensor changes from baseline (30-60 days before a COVID-19 test) to event (15-day window around a test) was compared between cohorts using one-way ANOVA. A date during the study window was randomly selected to serve as the event for control cases.

Results:
Comparing COVID-positive vs. COVID-negative vs. control, there was a greater change from baseline to event in respiratory rate (15% vs. 2% vs. 0.6% [p<0.0001]), activity (-44% vs. -12% vs. -6% [p<0.0001]), temperature (1% vs. 0.1% vs. -0.3% [p<0.0001]), and HeartLogic Index, a composite index using multiple sensors (227% vs. -11% vs. 2% [p=0.004]). Average sensor changes show prominent differences surrounding a COVID-19 test for COVID-positive compared to COVID-negative and control cases (
Figure
).

Conclusions:
Physiologic changes associated with COVID-19 infection are detectable using CIEDs. COVID-positive patients have significant increases in respiratory rate, temperature and HeartLogic index and significant decreases in activity compared to COVID-negative and untested patients. Future studies in a larger population will help characterize the utility of CIEDs in infection surveillance and physiologic worsening that should prompt medical attention.
Abstract 12381: Clinical Implications of
SCN5A
and
SCN10A
Loss of Function Variants in 169,610 Exomes Representing the General Population
Authors: Paludan-Mueller Christian , Larsen Simon , Ahlberg Gustav , Andreasen Laura , Svendsen Jesper Hastrup H , Kanters Jorgen K , Olesen Morten S
Published: April 2024

Background:
Genetic variation in the genes
SCN5A
and
SCN10A
has previously been associated with cardiac disease and conduction velocity through genome-wide association studies (GWAS) and rare variant analyses. The two neighboring genes constitute the much-investigated
SCN5A-SCN10A
locus, and it has been challenging to determine the region’s function as GWAS often identifies variants in non-coding regions. The cardiac function of
SCN5A
is well established whereas the role of
SCN10A
in cardiac conduction and disease remains disputed. The study focuses on
SCN10A
while
SCN5A
was included for comparative analyses.

Methods and Results:
We accessed the UK Biobank database, which contains data on >500,000 individuals. The recent exome release provides whole-exome sequencing data on 169,610 unrelated European individuals while resting ECGs are available on 44,987 individuals. We identified 668 individuals harboring LOF-variants (leading to early stop codon, frameshift or splice site disruption) in
SCN10A
and
SCN5A
with a MAF <1%. Among the 668 individuals, 543 individuals carried
SCN10A
variants, whereas 125 individuals held a variant in
SCN5A
. There were 88 and 37 different variants in
SCN10A
and
SCN5A
, respectively. From these individuals, we obtained 69 ECGs in sinus rhythm and 55 of these were recorded on individuals with a
SCN10A
LOF-variant and 14 ECGs were recorded on individuals with a
SCN5A
LOF-variant. Linear regression analyses established an association between
SCN5A
LOF-variants and prolongation of the PR-interval as carrying a variant corresponds to an average PR prolongation of 25.1 milliseconds (P = 0.001). There were no statistically significant alterations among other ECG parameters. Furthermore, we could not determine correlations of ECG parameters for
SCN10A
LOF-variants. A burden test on
SCN10A
and
SCN5A
LOF-variants could not establish a relationship with atrial fibrillation (P = 0.26 and P = 0.41, respectively) and heart failure (P = 0.92 and P = 0.17, respectively). Remaining possible disease associations could not be properly established due to low number of cases.

Conclusion:
These findings confirm the significance of
SCN5A
in cardiac conduction while questioning the function of
SCN10A
in human cardiac conduction and disease.
Abstract 12387: Porous Tip Radiofrequency Ablation Catheter Reduced Heart Failure Related Complications and Healthcare Utilization in Paroxysmal Atrial Fibrillation Patients
Authors: COSTEA ALEXANDRU I , Haile Bereket , Barone Adam , Schenthal Maddie , Romanowicz Kathrine , Joshi Kamal , Muth James N , Rajsheker Srinivas , Gache Larry , Boo Lee Ming , Hunter Tina D
Published: April 2024

Introduction:
Efforts to improve the safety of catheter ablation procedures have led to continuous improvements in catheter design. A 56-hole porous tip contact force (CF) catheter was developed to provide more uniform cooling with less fluid delivery than a prior 6-hole irrigated design, a change intended to reduce fluid overload and associated complications related to congestive heart failure (CHF).

Hypothesis:
We hypothesized that ablations using a 56-hole porous tip CF catheter would lead to reductions in CHF-related complications and healthcare utilization, compared to the prior 6-hole design.

Methods:
Consecutive de novo paroxysmal atrial fibrillation (PAF) ablations were performed between 2/14 - 3/19 by six operators at a single academic center. The 6-hole design was used through 12/16 with the 56-hole porous tip adopted in 10/16. Patient characteristics, procedural detail, and CHF-related complications or symptomatic presentation through 30 days were collected from electronic health records, as defined in table.

Results:
The population included 174 patients, age 61.1 ± 10.8 years, 67.8% male, with 25.3% having a history of CHF. Compared to the 6-hole design, the 56-hole catheter significantly reduced composite CHF-related complications within 7 days and CHF-related healthcare utilization within 30 days. In contrast to CHF reductions, non-CHF complications within 7 days were not different.

Conclusion:
In a real-world setting, a 56-hole porous tip irrigated CF catheter significantly reduced CHF-related complications and healthcare utilization in PAF patients when compared to the prior 6-hole design. This reduction may be related to the significant reduction in fluid delivery during the procedure. See table on next page.