bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 16644: Interstage Clinical Outcomes and Resource Utilization Among Babies With Single Ventricle: Results of A Randomized Cross-over Study Comparing Standard of Care (Notebook) to Tablet PC-Based Monitoring
Authors: Shirali Girish , Erickson Lori , Goggin Kathy , Apperson Jonathan , Bingler Michael , Tucker Dawn , Williams David , Bradley-Ewing Andrea , Staggs Vincent , Lay Amy , Rabbitt Leslie , Stroup Richard
Published: July 2021

Interstage outcomes for babies with single ventricle remain suboptimal. We have developed a tablet PC-based platform (CHAMP) for remote monitoring. This provides immediate access to data and instant alerts to the team. This study evaluates the caregiver experience with CHAMP, and its impact on interstage mortality, morbidity and resource utilization.

Methods:
All neonates with single ventricle who were discharged from 5/2014 to 5/2015 were prospectively enrolled. For 1 month after discharge, they were all monitored using a notebook. They were randomized to receive CHAMP at either 1 or 2 months post discharge. A month after randomization, caregivers had to choose either the notebook or CHAMP for the remainder of the inter-stage period. Charts were reviewed for mortality, unplanned readmissions and hospital charges. Caregiver experience was assessed through an exit survey.

Results:
We enrolled 24 babies (Norwood, n=11; BT shunt, n=9; no stage I at discharge (balanced circulation), n=3; hybrid, n=1). They were interstage for 3143 days. There was no interstage mortality in either group. While using CHAMP, families transmitted data on 77% of days. Resource utilization is summarized in the Table. CHAMP instant alerts and scheduled daily alerts led to 10 readmissions for issues that were not recognized by caregivers (low saturations (n=6) and poor feeding / weight gain (n=4). When given the option after randomization, 23 of 24 families chose CHAMP. At the end of monitoring, 23 completed an exit survey; when asked what form of monitoring they would choose if they had to do this over, 19 (82%) stated they would choose CHAMP, 3 would choose either, and 1 would choose the notebook.

Conclusions:
CHAMP monitoring was associated with significant decreases in unplanned readmission days, ICU days and hospital charges. CHAMP was well-accepted by caregivers, and would appear to facilitate outpatient care for the fragile population of interstage babies with single ventricle.
Abstract 16665: Caveolin-1 and α7nachr Interaction is Essential in Preventing Nicotine Induced Vascular Inflammatory Response in Mice
Authors: Guo Rui , Yan Zheyi , Ma Qin , Zhang Yanwei , Ma Xin , Wang Yajing
Published: July 2021

Nicotine is an independent risk factor of and associated with the development of atherosclerosis. Dysfunction of endothelial Cavolin-1 (Cav-1) can accelerate atherosclerosis progression via boosting inflammation response. However, the causative link between nicotine and atherosclerosis remains unknown. Here, we utilized molecular and cellular experiments revealed that in human endothelial cells (HUVECs), 10-6 M nicotine increased intracellular oxygen free radical generation, inhibited eNOS activity, augmented pathological NO production from iNOS, promoted nitrative stress (Nitrotyrosine), and increased adhesion molecule expression when compared with vehicle. In vivo administration of nicotine upregulated plasma adhesion molecule levels and significantly increased nitrotyrosine levels in vascular tissue (2±0.4 fold compared with untreated group, p<0.05). Bioinformatics analysis predicted that α7nAChR motif (151YIDVRWFPF159 and 168FGSWSYGGW176) may interact with Cav-1 via Cav-1 scaffolding domain (82DGIWKASFTTFTVTKYWFYR101). The bioinformatic analysis was confirmed by immunocytochemistry and immunoprecipitation showing that α7nAChR co-localizes with caveolin-1 (Cav-1) and these two molecules interact reciprocally. Although 10-6M nicotine did not alter expression levels of Cav-1, it significantly decreased the interaction between Cav-1 and nicotine receptor (α7nAchR). After siRNA Cav-1 gene silence, nicotine treatment further significantly increased ROS generation (1.37 + 0.33 times vs. scrambled siRNA, p<0.05), enhanced pathological NO production (1.35 ± 0.4 fold, p<0.05), and increased adhesion molecule expression (1.4 ±0.4 fold, p<0.05). AMPKα1, a sensor of oxidative stress, was phosphorylated after nicotine treatment. However, siRNA AMPK gene silence failed to block nicotine induced adhesion molecule expression. Taken together, these results demonstrated that reduced α7nAchR/Cav-1interaction plays an important role in nicotine induced endothelial inflammatory response; this inflammation signal pathway is AMPK independent. Preserving and strengthening stability of Cav- 1/α7nAchR interaction is a potential target in treatment of vascular dysfunction caused by smoking.
Abstract 16716: Intravascular Injection of Sendai Virus Vector Carrying Continuously cGMP Producing Mutant of Type B Natriuretic Peptide Receptor Can Ameliorate Pulmonary Arterial Hypertension
Authors: Nawa Nobutoshi , Ishida hidekazu , Katuragi Shinichi , Baden Hiroki , Takahashi Kunihiko , Kogaki Sigetoyo , Higeno Ryota , Torigoe Fumiko , Mihara Seiko , Narita Jun , Miura Koji , Ozono Keiichi
Published: July 2021

Introduction:
Type B natriuretic peptide receptor (NPR-B) is one of the transmembrane guanylyl cyclases and synthesizes cGMP on C-type natriuretic peptide binding. We have found a novel constitutively active mutation in the NPR-B gene in a family case showing overgrowth and bone anomalies. Previously, we constructed adenovirus vectors carrying this mutant NPR-B and administered to Sugen PAH rats intratracheally to investigate its therapeutic effect. However, the use of adenovirus vectors actually caused inflammatory host response in the lung.

Objective:
Sendai virus vector (SeV) is well known for its high transduction efficiency as well as the low toxicity. Recently, the results of a Phase I/IIa clinical study of SeV in human peripheral arterial disease have been reported. The objective of this study was to investigate the therapeutic effect of SeV carrying constitutively active mutant of NPR-B for PAH in rats.

Methods and Results:
We constructed SeV carrying wild-type (WT), and mutant (Mut) NPR-B. Control SeV carrying Azami-Green was purchased from MBL (Medical & Biological laboratories, Nagoya, Japan). The overexpression of the mutant in human pulmonary artery smooth muscle cells by SeV induced significant increase in cGMP levels (control, 0.193±0.115 pmol/mL; WT-NPR-B, 38.3±29.6 pmol/mL; Mut-NPR-B, 2460±577 pmol/mL; n=3; p<0.01), and suppressed proliferation as assessed by 5-ethynyl-2′-deoxyuridine (EdU) incorporation (EdU positive ratio: control, 0.18±0.017; WT, 0.12±0.023; Mut, 0.085±0.010; n=6; P < 0.05).

In Sugen PAH rats, intravascular administration of SeV carrying Mut-NPR-B significantly decreased right ventricular systolic pressure (Control, 61.4±8.4 mmHg; WT, 61.5±5.4 mmHg; Mut, 46.9±4.9mmHg; n=6; p<0.01) and the ratio of right ventricular/left ventricular pressure (Control, 0.67±0.05; WT, 0.70±0.03; Mut, 0.53±0.09; n=6; p<0.01). Furthermore, the proportion of occluded arteries was lower in Mut transduced rats than in control or WT transduced rats histologically.

Conclusions:
The CNP/NPR-B signaling pathway is an additional therapeutic target for the treatment of PAH. The enhancement of CNP/NPR-B pathway could ameliorate both intimal and medial remodeling of pulmonary artery in PAH.
Abstract 16791: Oral Administration of Synthetic Prostacyclin Agonist Ono-1301 Prevents Deterioration of Cardiac Performance by Preserving Cardiac Structural Proteins in the Delta-sarcoglycan-deficient Hamster: Promising Treatment for Patients With DCM
Authors: Miyagawa Shigeru , Sakai Yoshiki , Fukushima Satsuki , Masuda Shigeo , Saito Atsuhiro , Toda Koichi , Sawa Yoshiki
Published: July 2021

Background:
Although drugs such as beta blockers are reported to be effective for dilated cardiomyopathy (DCM), they are only effective in selected patients, and new therapeutics based on different mechanisms are still needed. We hypothesized that synthetic prostacyclin agonist (ONO-1301) would preserve the structural proteins in distressed cardiomyocytes, thus attenuating the deterioration of cardiac performance in the delta sarcoglycan-deficient hamster.

Methods and Results:
In an in vitro study, ONO-1301 was added to the culture medium of non-myocyte cells and the expression of several cytokines including VEGF was examined by ELISA. For the in vivo study, ONO-1301 (A: 3, n=5, B: 1, n=6, C: 0.3, n=7, D: 0.1 mg/kg/dose, n=7) was orally administered to delta-sarcoglycan-deficient hamsters every day from 8 to 20 weeks after birth. The control group (n=6) was untreated. Functional performance was evaluated by US before, 2, 4, 6, and 8 weeks after administration of ONO-1301. A histological analysis focusing on basement-membrane structural proteins, such as α-sarcoglycan, β-sarcoglycan, and α-dystroglycan, fibrosis, and hypertrophy was performed. In vitro, ONO-1301 enhanced the cytokine expressions dose dependently. In vivo, systolic function (EF) was gradually increased in the ONO-1301-treated groups, while it showed significant deterioration in the control group (45.7±2.9, 42.0±2.6, 32.3±1.0, 30.3±2.5, 26.3±2.7%, in groups A, B, C, D, and control, respectively, P<0.05). ONO-1301 also significantly attenuated the LV dilatation in a dose-dependent manner. Immunostaining revealed that all the cardiac structural proteins were preserved in the basement membrane of cardiomyocytes in the 3.0 mg/kg ONO-1301 treatment group, while they disappeared in the control. The % fibrosis and cell hypertrophy were significantly attenuated in the ONO-1301-treated group compared with the control.

Conclusions:
Oral administration of synthetic prostacyclin agonists, which can enhance cytokine expressions in non-myocyte cells, may preserve cardiac structural proteins in the delta sarcoglycan-deficient hamster, to maintain cardiac performance. This promising drug may inhibit the progression of the disease pathology in DCM, prolonging their life.
Abstract 16807: Role of Rotor Activation Within the Pulmonary Vein as the Driving Sources for Atrial Fibrillation: Three-dimensional Analysis using a Non-contact Mapping System
Authors: Yamabe Hiroshige , Kanazawa Hisanori , Hoshiyama Tadashi , Ito Miwa , Kaneko Shozo , Ogawa Hisao
Published: July 2021

Background:
It has been suggested rotor which is located within the pulmonary vein (PV) acted as the driving sources of atrial fibrillation (AF). However, it has never been confirmed whether or not the rotor exists within PV in human.

Objectives:
We analyzed the activation sequence within the PV during AF and examined how the PV acted as the driving sources of AF.

Methods:
Selective endocardial mapping of left superior PV (LSPV) was performed during AF in 11 paroxysmal AF patients using a non-contact mapping system (EnSite 3000). Presence of rotor activation was defined when the circular activation around the functional block line once completed its whole reentrant activation. We analyzed the relation between the pivoting activation and the rotor activation. To define the preferable site of rotor and pivoting activation, we also analyzed the relation between the location of rotor and pivoting activation and region of the complex fractionated electrogram (CFE) recording site.

Results:
Rotor activation was observed with a mean number of 4.6±3.6 times/sec. CFE was observed at the roof (n=5), ridge (n=11) and carina (n=7) of the proximal half of LSPV with a mean area of 9.1±3.4 cm2. The number of rotor activation observed at the CFE area was significantly higher than that at the non-CFE area (4.1±3.9 vs. 0.7±1.2 times/sec, p=0.025). Total frequency of pivoting activation was 37.0±14.7 times/sec. Pivoting activation involved in the rotor activation was significantly lower than that not involved in the rotor activation (8.8±8.1 vs. 27.7±15.8 times/sec, p=0.0116). Regarding the CFE area, pivoting activation involved in the rotor activation was also significantly lower than that not involved in the rotor activation (8.4±8.2 vs. 24.1±12.0 times/sec, p=0.0105). However, there was no difference between the frequencies of pivoting activation with and without rotor activation in the non-CFE area (1.0±2.0 vs. 3.6±6.1 times/sec, p=NS).

Conclusions:
Rotor activation was observed at the proximal portion of the LSPV coincided with the location of CFE area. However, most of pivoting activation was not involved in the rotor activation. These suggest that AF was driven by the other meandering propagation associated with frequent non-stable pivoting activation over the CFE area.
Abstract 16822: Dust Storms in the United States are Associated With Increased Cardiovascular Mortality
Authors: Crooks James L , Cascio Wayne , Percy Madelyn , Reyes Jeanette , Neas Lucas , Hilborn Elizabeth
Published: July 2021

Introduction:
Extreme weather events such as dust storms are predicted to become more frequent as the global climate warms through the 21st century. Studies of Asian, Saharan, Arabian, and Australian dust storms have found associations with cardiovascular and total non-accidental mortality and hospitalizations for stroke. However, the only population-level epidemiological work on dust storms in the United States was focused on a single small metropolitan area (Spokane, WA), and it is uncertain whether its null results are representative of the country as a whole.

Hypothesis:
Dust storms in the United States are associated with daily cardiovascular mortality.

Methods:
Dust storm incidence data (N=141), including date and approximate location, as well as meteorological station observations, were taken from the U.S. National Weather Service. County-level mortality data for the years 1993-2005 were acquired from the National Center for Health Statistics. Ambient particulate matter monitor concentrations were obtained from the U.S. Environmental Protection Agency. Inference was performed used conditional logistic regression models under a case-crossover design while accounting for the nonlinear effect of temperature.

Results:
We found a 9.5% increase in cardiovascular mortality at a two-day lag (95% CI: [0.31%,19.5%], p = 0.042). The results were robust to adjusting for heat waves and ambient particulate matter concentrations. Analysis of storms occurring only on days with <0.1 inches of precipitation strengthened these results and in addition yielded a mean daily increase of 4.0% across lags 0-5 (95% CI: [0.07%,20.8%], p = 0.046). In Arizona, the U.S. state with the largest number of storms, we observed a 13.0% increase at a three-day lag (CI: [0.40%,27.1%], p = 0.043).

Conclusions:
Dust storms in the U.S. are associated with increases in lagged cardiovascular mortality. This has implications for the development of public health advisories and suggests that further public health interventions may be needed.

Disclaimer:
This work does not represent official U.S. Environmental Protection Agency policy.
Abstract 16893: Subclinical Decrease in Myocardial Function in Asymptomatic Infants of Diabetic Mothers: A Tissue Doppler Study
Authors: Zablah Jenny E , Gruber Dorota , Hayes Denise A
Published: July 2021

Introduction:
Infants of diabetic mothers (IDMs) with cardiac hypertrophy are recognized to have impaired myocardial performance, but less is known about ventricular function in those without hypertrophy. We hypothesized that, in asymptomatic newborns with normal echocardiograms, tissue Doppler imaging (TDI) indices of cardiac function would be decreased in IDMs compared to controls.

Methods:
This retrospective case-control study involved IDMs ≥ 36 weeks gestational age, at 0 to 7 days of life. Subjects with cardiorespiratory symptoms, ventricular hypertrophy or dysfunction, or any echocardiographic abnormality (other than a patent ductus arteriosus before 4 days of life, or a patent foramen ovale) were excluded. Each subject was matched with 3 controls (healthy infants of non-diabetic mothers) by age (0-24, 25-48, 49-72, or > 72 hours of life), birth weight (± 0.5 kg), body surface area (± 0.03 m
2
), and by the ultrasound system utilized. TDI systolic (S’), early diastolic (E’), and late diastolic (A’) velocities were measured at the mitral valve (MV) annulus, basal ventricular septum, and tricuspid valve (TV) annulus, and were averaged from 3 consecutive cardiac cycles. Early Doppler inflow velocity to E’ ratios (E/E’) were calculated.

Results:
Seventy cases (39 male) were identified: first 24 hours (h) of life (n=18), 25-48 h (n=22), 49-72 h (n=14), and > 72 h (n=16). Maternal diabetes was gestational in 60 cases, and pre-existing in 10. Median gestational age was 38 6/7 weeks (range 36-41 2/7), median birth weight 3.65 kg (2.56-5.38), and median BSA 0.22 m
2
(0.17-0.27). Ultrasound system vendors included Siemens
®
(n=46), Philips
®
(n=23), and General Electric
®
(n=1). Cases were matched with 210 controls.

IDMs had significantly lower S’ (
p
≤ 0.05) and E’ (
p
≤ 0.01) velocities, and significantly higher E/E’ ratios (
p
≤ 0.01) at the MV, basal septum, and TV compared to controls (Wilcoxon rank-sum test). There were no significant differences in A’ values between groups. Intraclass correlation demonstrated 84-99% interobserver and 98-99% intraobserver reliability.

Conclusions:
In asymptomatic newborn IDMs without cardiac hypertrophy, TDI suggests a subclinical decrease in systolic and diastolic myocardial function compared to controls.
Abstract 16918: A Transient Increase in Left Ventricular Load Leads to Cardiac Troponin I Release in the Absence of Myocardial Ischemia
Authors: Weil Brian R , Young Rebeccah F , Iyer Vijay , Suzuki Gen , Canty John M
Published: July 2021

Introduction:
Although elevated serum cardiac troponin I (cTnI) concentrations are widely used as a biomarker for the detection of myocardial infarction, increased serum cTnI levels have been observed in the absence of ischemia in fluid overload states such as renal failure and advanced heart failure.

Hypothesis:
Transient left ventricular (LV) stretch induced by a reversible elevation in preload without ischemia leads to significant transcardiac cTnI release.

Methods:
Propofol-sedated swine (n=12) received intravenous phenylephrine (PE; 300 μg/min) for one hour to transiently raise LV end-diastolic pressure (EDP) to ∼30 mmHg. Hemodynamics were monitored throughout the experiment and myocardial perfusion was measured at baseline and during PE with fluorescent microspheres to exclude subendocardial ischemia. Serial blood sampling from the aorta and coronary sinus was performed to assess transcardiac cTnI release before, during, and after PE infusion.

Results:
PE induced a significant rise in mean arterial pressure (MAP; from 99 ± 5 to 172 ± 5 mmHg, P<0.05) and LVEDP (from 16 ± 2 to 30 ± 3 mmHg, p<0.05) that normalized 15 minutes after the infusion was stopped (MAP: 94 ± 7 mmHg, LVEDP: 17 ± 2 mmHg). Subendocardial blood flow was unaffected by PE infusion (0.9 ± 0.1 mL/min/g vs. 0.8 ± 0.1 mL/min/g at baseline). Serial blood sampling revealed significant transcardiac cTnI release 60-minutes after cessation of PE (Table). The next day, circulating cTnI levels remained elevated but there was no longer a significant gradient between the aorta and coronary sinus.

Conclusions:
These results demonstrate that a transient increase in LV preload produces measurable transcardiac cTnI release that results in sustained elevations in circulating cTnI. This response occurs without a change in subendocardial blood flow, indicating that elevations in hemodynamic load may provoke cardiomyocyte damage independently of ischemia-induced cell necrosis in the normal heart.
Abstract 17098: Evaluation of a Non-laboratory-based Cardiovascular Disease Risk Score in Predicting Cardiovascular Mortality in the Southern Community Cohort Study
Authors: Singh Jai , Kabagambe Edmond K , Xu Meng , Gaziano Thomas A , Wang Thomas J , Blot William J , Gupta Deepak K , Lipworth Loren
Published: July 2021

Introduction:
Cardiovascular disease (CVD) risk prediction guides clinical recommendations regarding primary prevention strategies. Recently, a non-laboratory-based CVD risk score was derived and validated in several populations. We evaluated the performance of the non-laboratory CVD risk score among individuals of low socioeconomic status in the southeastern US, with high CVD incidence rates.

Methods:
The Southern Community Cohort Study (SCCS) is a prospective cohort study of black and white adults enrolled primarily from community health centers in the southeastern US between 2002-2009. We calculated c-statistics and 95% confidence intervals (CI) to assess the performance of the non-laboratory risk score in discriminating 5- year risk of CVD death (ICD-10 I00-I99) in 14,243 participants (median enrollment age 51 yrs; 74% black, 71% female, 61% income < $15,000 yr) with no history of MI/CABG or stroke at baseline and with complete data on all input variables (age, sex, smoking, diabetes mellitus, reported hypertension (HTN), measured SBP, and BMI). Reported HTN was substituted for anti-HTN therapy, used in the original risk score, because the latter was available only for a subset of the SCCS population. However, among this subset, 82% of individuals who reported HTN also reported use of anti-HTN drugs.

Results:
CVD risk factors were common: HTN (66%), smoking (59%), diabetes (29%), median SBP 130 mmHg, and median BMI 31 kg/m2. CVD death occurred in 263 participants (1.8%). The non-laboratory CVD risk score demonstrated poor discrimination for CVD mortality, with c-statistics of 0.65 (95% CI: 0.61-0.68) overall and 0.64 (0.59-0.69), 0.65 (0.6-0.7), 0.67 (0.63-0.71) and 0.58 (0.51-0.65) for males, females, blacks and whites, respectively. In an additional logistic regression model fit to the SCCS data, the inclusion of education and income did not substantially improve model performance; overall c-statistic 0.70 (0.67-0.73).

Conclusion:
In this population of predominantly low-income blacks and whites, a non-laboratory CVD risk score did not perform well in predicting CVD death in any of the race and gender groups. Future studies are warranted to develop algorithms for identifying individuals at increased CVD risk in low resource populations.
Abstract 17101: Vasoprotective Properties of HDL Improve Early Ater Roux-en-y Gastric Bypass but Not After Diet Treatment: The Superior Cardiometabolic Benefits of RYGB
Authors: Osto Elena , McLoughlin Eve , Doytcheva Petia , Charakida Marietta , Finer Nicholas , Van Gaal Luc , Deanfield John , Luescher Thomas
Published: July 2021

Introduction:
Roux-en-Y gastric bypass (RYGB) reduces cardiometabolic risk through different potential mechanisms. High density lipoprotein cholesterol (HDL-C) changes might explain part of this benefit.

Hypothesis:
We assessed the effect of RYGB on HDL vasoprotective properties in comparison with a hypocaloric diet-induced weight loss.

Methods:
HDL was isolated from serum of obese patients (BMI > 35 kg/m2) before and 6 months after RYGB (n=32) or diet (n=32). In endothelial cells stimulated with HDL, we quantified nitric oxide (NO) production by DAF-2 fluorescence and paraoxonase-1 antioxidant activity (PON-1). Total cholesterol, low density lipoprotein (LDL-C), HDL-C, and triglycerides (TG) as well as glucose plasma fasting levels were measured.

Results:
At baseline there was no significant difference in mean body weight (BW) and BMI between RYGB and diet patients (119.9 Kg; 42kg/m2 vs. 110.9 kg; 37.4 kg/m2, respectively, p=0.06). At 6 months, BW and BMI were not different (RYGB: 94kg; 33 kg/m2; diet: 99kg; 33.4 kg/m2, p=ns). In both groups, mean total cholesterol and TG were reduced; LDL-C decreased only after RYGB. Total HDL-C increased 6 months after both interventions (RYGB: 1.2±0.5 baseline vs 1.3±0.4 after 6months; diet 1.1±0.25 baseline vs 1.3±0.3 after 6months, p<0.05). However, only RYGB improved the vasoprotective HDL-stimulated NO production (RYGB: 234.2±178.0 vs diet 98.8±76.4 arbitrary units, p<0.0001) and HDL-associated PON-1 activity (RYGB: 40% vs diet: 9% increase compared to baseline; p<0.0001). Fasting glucose levels improved in both groups and were not different at 6 months between the two interventions.

Conclusions:
Our study shows that although HDL concentration increased after RYGB and diet-induced BW loss, only RYGB restored endothelial protective HDL properties even though patients were still obese. This suggests that BW loss is not sufficient or critical to improve the protective properties of HDL, unless accompanied by yet unknown surgery-specific effects.
Abstract 17105: Higher Maximum Temperatures Associated With Worse Outcomes in Patients With Pyrexia Following Rewarming From Post-arrest Targeted Temperature Management
Authors: Grossestreuer Anne V , Gaieski David F , Wernovsky Magda B , Wiebe Douglas J , Abella Benjamin S
Published: July 2021

Background:
Post-arrest pyrexia has been associated with worse outcomes in recent clinical studies. While TTM serves as prophylaxis against pyrexia during active temperature management, it remains unknown to what extent the degree of post-TTM pyrexia relates to survival and neurologic outcomes. We sought to evaluate the association between outcomes and maximum temperature (Tmax) within 72 hours post-rewarming in patients who had Tmax≥38 °C.

Hypothesis:
We hypothesized that increased Tmax a patient with pyrexia reaches in 72h after TTM discontinuation is associated with worse neurologic and survival outcomes.

Methods:
We identified 382 TTM-treated patients treated at 14 hospitals between 2005-2014 who had out-of-hospital arrests and serial temperatures recorded during the 72h after returning to normothermia (≥36.5 °C) post-TTM. Our primary outcome was neurologic status (Cerebral Performance Category (CPC) score dichotomized into “good” (1-2) and “poor” (3-5)). Highest recorded temperature in 72h post-TTM after returning to a temperature ≥36.5°C was Tmax. Multiple imputation was used to manage covariate missingness.

Results:
147 (39%) patients had documented pyrexia within 72h post-rewarming. In patients with pyrexia, 60% were male, 44% had initial pulseless rhythm of VF/VT, median duration of arrest was 20 (IQR: 13, 30) mins, 49% survived to hospital discharge, and 52 (36%) had a CPC score 1-2 at hospital discharge. Tmax ranged from 38.0-42.2°C, with mean Tmax of 38.7±0.7°C. Median time to Tmax was 19h (IQR: 8, 42). In univariate analysis, higher Tmax was associated with worse neurologic outcomes (OR: 0.38 (95% CI: 0.18-0.80); p=0.01) and survival (OR: 0.41 (95% CI: 0.22-0.79); p=0.01). When controlling for year of arrest, hospital, initial rhythm, sex, witnessed arrest, arrest duration, and age, this relationship was still significant, with each increase in 1°C corresponding to 77% reduction in odds of having good neurologic outcome (aOR: 0.23 (95% CI: 0.08-0.67); p=0.007) and 65% reduction in odds of surviving to hospital discharge (aOR: 0.35 (95% CI: 0.15-0.82); p=0.015).

Conclusion:
Increased maximum temperature in patients with pyrexia post-rewarming is associated with increased likelihood of poor neurologic and survival outcomes.
Abstract 17110: Risk Factors for Hepatic Fibrosis in Children and Adolescents After Fontan Operation
Authors: Goldberg David J , Surrey Lea F , Lin Henry C , Glatz Andrew C , O'Byrne Michael L , Rome Jonathan J , Dodds Katie , Rand Elizabeth , Russo Pierre , Rychik Jack
Published: July 2021

Introduction:
Congestive hepatopathy is increasingly recognized as a complication of Fontan physiology. Prospective data regarding the incidence of hepatopathy and risk factors for its development are lacking.

Methods:
Liver biopsies were obtained as part of a routine program of comprehensive end-organ evaluation offered to all patients >10 years after Fontan operation (FO) through the Single Ventricle Survivorship Program. Evaluation included cardiac catheterization and contemporaneous percutaneous liver biopsy. Quantitative determination of hepatic fibrosis was performed using Sirius red staining for collagen with automated calculation of percent positive staining per slide. Patient specific characteristics, echocardiographic findings, and hemodynamic measures were assessed and evaluated as potential risk factors for collagen deposition using Pearson correlation. Differences in collagen deposition (%CD) between subgroups were assessed using the student t-test.

Results:
The cohort consisted of 67 patients (36 male) at mean age of 17.3 ±4.5 years and mean time from Fontan of 14.9 ±4.5 years. Right ventricular morphology was present in 37 subjects; 30 with hypoplastic left heart syndrome. Mean %CD by Sirius red staining was 23.8 ±9.5% (range 8.7-49.4%) as compared to 2.6 ±0.3% in controls. There was significant correlation between time from Fontan and degree of Sirius red staining (r=0.33, p=0.006). Serum liver enzymes and platelet count did not correlate with %CD. The median inferior vena cava (IVC) pressure was 13 mmHg (range 6-24 mmHg) and did not correlate with %CD. There was no difference in %CD between those with a measured IVC pressure ≥13 mmHg versus those with a pressure <13 mmHg. There was no difference in %CD based on ventricular morphology or severity of atrioventricular valve insufficiency.

Conclusion:
In this cohort of predominantly asymptomatic children and adolescents electively evaluated after FO, all exhibited evidence for hepatic fibrosis as measured by collagen deposition in the liver. Time from FO was the only factor in this cohort that was significantly associated with collagen. These findings demonstrate that liver fibrosis is an inherent feature of Fontan physiology and that the degree of fibrosis increases over time.
Abstract 17134: Cardiorenal Syndrome Arising From Chronic Diabetes Causes Maladaptive Carbohydrate Utilisation in the Heart and Kidneys
Authors: Schroeder Marie A , Bugyei-Twum Antoinette , Chen Albert , Tsui Albert , Mitchell Michelle , Desjardins JF , Kabir G , Cunningham Charles H , Connelly Kim A
Published: July 2021

Clinical and epidemiological data have identified a cardiorenal syndrome (CRS), in which heart and/or kidney failure accelerates dysfunction in the other organ. There is a need for new therapeutics targeting the mechanisms that cause CRS, in order to treat the whole patient. Here, we tested the hypotheses that 1) chronic diabetes (aged Goto-Kakizaki [GK] rats) would yield a model of CRS, and 2) assessing
in vivo
cardiorenal metabolism using hyperpolarized
13
C MR spectroscopy (MRS) would identify targets for CRS therapy. Statistical significance between GK rats and Wistar controls was considered at P<0.05. Glycated hemoglobin confirmed that GK rats were diabetic at 20 weeks. Forty-week-old GK rats (n=6) developed proteinuria, LV hypertrophy, and pulmonary congestion. Invasive pressure-volume loops (n=5) demonstrated preserved systolic, yet impaired diastolic, function. Histology demonstrated myocyte and glomerular hypertrophy, interstitial fibrosis and glomerulosclerosis. Intravenous infusion of hyperpolarized [1-
13
C]pyruvate (n=4), followed by MRS data acquisition that alternated between heart and kidney, indicated that carbohydrate metabolism was reprogrammed to promote lactate production over oxidation. In the heart, this was evidenced by reduced pyruvate dehydrogenase flux to form
13
C-bicarbonate, increased
13
C-lactate production, and reduced
13
C-alanine production. In the kidney,
13
C-lactate was increased at the expense of
13
C-alanine. Metabolic reprogramming to produce cardiorenal lactate was likely mediated by inflammation: in both organs, macrophage infiltration and expression of toll like receptor 4 protein were increased. Increased expression of renal
Pck1
and
G6pc
mRNA indicated involvement of maladaptive systemic gluconeogenesis in CRS pathogenesis. Normalizing whole-body carbohydrate utilization represents a novel target for therapy of diabetes-induced CRS.
Abstract 17136: MicroRNA-181b Inhibition Stabilises Abdominal Aortic Aneurysms by Promoting Collagen Accumulation and Elastin Deposition
Authors: Di Gregoli Karina , Mohamad Anuar Nur Najmi , George Sarah J , Johnson Jason L
Published: July 2021

Increased matrix metalloproteinase (MMP) activity, and related collagen and elastin degradation as a result of macrophage accumulation, are key characteristics of abdominal aortic aneurysm (AAA) progression and rupture. Accordingly targeting MMPs or promoting expression of the endogenous tissue inhibitor of metalloproteinases (TIMPs), may represent novel therapeutic strategies to prevent AAA progression and rupture.

To closely mimic human AAA, we used an angiotensin II (AngII)-infused, high fat-fed apolipoprotein E knockout mouse model. Sudden death due to aortic dissection/rupture, was significantly increased (30%, p<0.001, n=20) in TIMP3 KO mice compared to wild-type controls, supporting a protective role for TIMP3 in AAA progression. Moreover Q-PCR revealed that microRNA (miR)-181b, a validated repressor of TIMP3 protein expression, was up-regulated 22-fold (n=6, p<0.001) in human AAA compared to non-aneurysmal sites. In vitro, miR181b inhibition increased macrophage TIMP3 protein expression 3-fold (n=4, p<0.05), highlighting miR181b inhibition as a potential approach to retard AAA progression. Indeed using a miR181b inhibitor, AAA development and inflammation was retarded in AngII-infused high fat-fed ApoE KO mice. This effect was characterised by a 56% reduction in macrophage content (n=5, p<0.05), augmented collagen content 1.9-fold (n=5, p<0.05) and collagen fibre thickness (+24%, p<0.05) in AAAs compared to scrambled-miR control animals. AAA elastin content was also increased (1.5-fold, n=5, p<0.05) in miR181b inhibitor treated mice versus controls. Collagen accumulation was TIMP-3 dependent as miR-181b inhibition did not affect collagen levels in TIMP-3 KO mice. However elastin content remained elevated in miR-181b inhibitor treated TIMP3 KO mice (2-fold, n=6, p=0.001), suggesting a TIMP-3 independent mechanism. In vitro miR181b inhibition in smooth muscle cells revealed a 2.5-fold increase in elastin production (n=3, p<0.05), supporting a direct role for miR-181b in elastin regulation.

Collectively our data show that miR181b inhibition stabilises AAA through a dual beneficial effect, by promoting collagen preservation via TIMP3 modulation, and through directly increasing elastin production and deposition.
Abstract 17212: 30-day All-cause Readmission is Associated With a Significantly Higher Subsequent All-cause Mortality and Costly Readmissions Among Older Medicare Beneficiaries Hospitalized for Heart Failure
Authors: Arundel Cherinne , Khosla Rahul , Faselis Charles , Morgan Charity J , Zhang Sijian , Blackman Marc , Fletcher Ross D , Wu Wen-Chih , Butler Javed , Fonarow Gregg C , Deedwania Prakash , White Michel , Aronow Wilbert S , Filippatos Gerasimos S , Anker Stefan D , Ahmed Ali , Allman Richard M
Published: July 2021

Background:
Among ambulatory patients with heart failure (HF), hospital admission is associated with higher subsequent mortality. HF is the leading cause of 30-day all-cause readmission, reduction of which is a goal of the Affordable Care Act. We examined the association of 30-day all-cause readmission with subsequent all-cause mortality in a propensity-matched cohort of hospitalized HF patients.

Methods:
Of the 8049 Medicare beneficiaries hospitalized for HF and discharged alive from 106 U.S. hospitals (1998-2001), 7578 were alive 30-day post-discharge, of which 1519 had 30-day all-cause readmission. Using propensity scores for 30-day all-cause readmission, we assembled a matched cohort of 1516 pairs of patients with and without 30-day all-cause readmission, balanced on 34 baseline characteristics.

Results:
During 2-12 months of post-discharge follow-up, all-cause mortality occurred in 41% and 27% of matched patients with and without 30-day all-cause readmission, respectively (HR, 1.68; 95% CI, 1.48-1.90; p<0.001; Figure). During a mean post-index follow up of 3 (max 9) years, patients with 30-day all-cause readmissions (vs. without) had higher total of post-index readmissions (mean, 6.9 vs 5.1; p<0.001), longer cumulative length of stay (mean, 51 vs 43 days; p<0.001), and higher charges (mean, $129,175 vs. $114,787; p=0.012) and payments (mean, $38,972 vs. $34,025; p=0.001) from those readmissions.

Conclusions:
Among hospitalized patients with HF 30-day all-cause readmission is associated with higher subsequent mortality, number of readmissions and costs, and longer cumulative length of stay.
Abstract 17213: Does Left Ventricular - Mitral Ring Mismatch Predict Risk of Recurrent Mitral Regurgitation Post Annuloplasty in Patients With Ischemic Mitral Regurgitation?
Authors: CAPOULADE ROMAIN , Zeng Xin , Overbey Jessica R , Ailawadi Gorav , Alexander John , Ascheim Deborah , Bowdish Michael , Gelijns Annetine , Grayburn Paul , Kron Irving , Mack Michael , Melnichouk Serguei , Michler Robert , Mullen John , O'Gara Patrick , Parides Michael , Smith Peter K , Voisine Pierre , Hung Judy ,   CTSN Investigators
Published: July 2021

Background:
In ischemic mitral regurgitation (IMR), ring annuloplasty is associated with a 30-50% rate of recurrent IMR. Ring size is based on inter-trigonal distance without consideration of LV size. However, LV size is an important determinant of mitral valve (MV) leaflet tethering pre and post repair. We aimed to determine if LV - MV ring mismatch (mismatch of LV size relative to ring size) is associated with recurrent IMR in patients post ring.

Methods:
Patients with moderate or severe IMR from the two cardiothoracic surgical network IMR trials (NCT-00806988 and 00807040) who received MV repair were examined at 1-year post-surgery. Baseline LV size was assessed by LV end-diastolic (LVIDed) and end-systolic (LVIDes) dimensions. LV- MV ring mismatch was calculated by dividing LV size by ring size (LVIDed/ring and LVIDes/ring). Multivariable regression models for each of these measures adjusting for age, sex, baseline LVEF and severe IMR were used to determine association with recurrent (≥moderate) IMR at one year.

Results:
1-year post ring, 45 (21%) of 216 repair patients had ≥moderate IMR. In univariate analysis, larger LVIDes (p=0.02) and higher LVIDes/ring (p=0.006) were associated with recurrent IMR; LVIDed and LVIDed/ring was not (p>0.05). In multivariable models both LVIDes/ring (p=0.01) and LVIDes (p=0.02) remained significantly associated with 1-year IMR recurrence; the odds of recurrence increasing by a relative 72% per 10% increase in LVIDes/ring and by 70% per 10mm increase in LVIDes.

Conclusion:
We found that increasing LV-MV ring mismatch and LVIDes are both associated with increased risk of IMR recurrence. The high correlation between LVIDes and LVIDes/ring in our data precludes a definitive determination of the relative contribution of each measure to the increased risk of IMR recurrence. While further research is needed to confirm our findings, these data may be helpful in guiding ring size to prevent recurrent IMR in patients undergoing MV repair.
Abstract 17219: Increased Aortic Stiffness Following Intrauterine Exposure to Chronic Hypoxia in Rats
Authors: Kumar Praveen , Morton Jude , Davidge Sandra T , Cheung Po-Yin , Hornberger Lisa K
Published: July 2021

Background:
We have previously demonstrated in rats that fetal hypoxia is associated with altered left ventricular (LV) diastolic function beginning in early postnatal life (2 weeks). In the present study we hypothesized that intrauterine hypoxia exposure alters aortic stiffness which may contribute to the evolution of myocardial dysfunction after birth.

Methods:
Six pregnant rats were exposed to hypoxic conditions (11.5% FiO2) from E15-21and 3 were maintained in normoxic conditions. After delivery, 4 neonatal rats from each group were examined longitudinally at day 1, 3, and week 1, 2, 4, 8 for changes in aortic stiffness. Pups were anesthetized by face mask with 1.5% isoflurane. Aortic stiffness was assessed by measuring the pulse wave velocity (PWV) in the ascending aorta at 3 points: 1. Proximal to the branch of the first brachiocephalic artery 2. At the level of the diaphragm and 3. Just above the aortic bifurcation into the iliac arteries. T1 was the time interval from the peak of the R wave by ECG to onset of flow in the ascending aorta and T2 from peak of the R wave to onset of flow in either the mid aorta or distal aorta. The distance from the suprasternal notch to the subxiphoid process and to the anterior superior iliac spine was measured in each animal. The PWV was calculated using the following equation: [distance/(T2-T1)]. Three consecutive tracings were assessed and the PWV averaged for each study. Statistical analysis was performed using a 2-way ANOVA.

Results:
In pups exposed to fetal hypoxia, PWV was significantly increased (p≤0.001) compared to controls at day 1 (4.8±1.5 vs. 2.3±0.2 m/s), day 3 (5.5±0.3 vs. 2.6±0.1 m/s) and week 1 (4.4±0.4 vs. 2.8±0.1 m/s). Interestingly, there was an interaction of time and fetal exposure (p=0.006) whereby PWV values converged from weeks 2 - 8 such that fetal exposure to hypoxia no longer had an effect. No correlation was found between LV diastolic function parameters and aortic PWV in the fetal hypoxia rats at any postnatal age.

Conclusion:
Prenatal exposure to hypoxia was associated with increased aortic stiffness during early development. The lack of a relationship between LV diastolic function and aortic stiffness could suggest these represent independent effects of fetal hypoxia exposure.
Abstract 17246: Risk Factors for Major Bleeding Events in Rivaroxaban Users With Atrial Fibrillation: A Nested Case-control Study
Authors: Tamayo Sally , Simeone Jason , Nordstrom Beth , Patel Manesh , Yuan Zhong , Sicignano Nicholas , Peacock W. Frank
Published: July 2021

Introduction:
Rivaroxaban is a novel oral anticoagulant indicated to reduce the risk of stroke and systemic embolism in patients with non-valvular atrial fibrillation (NVAF). Anticoagulation therapies carry a risk of major bleeding (MB), for which patient characteristics may play a role.

Methods:
Using data obtained from the Department of Defense (DoD), we examined risk factors for MB within a cohort of rivaroxaban-treated patients with NVAF using a nested case-control design. Cases with MB were selected by a validated claims-based algorithm that approximates the definition of MB used in clinical trials. Incidence density sampling was used to identify 5 controls without MB for each case. Controls had the same year of entry into the cohort and were at risk for a MB event at the time of each matched case’s event (index date). Potential risk factors for MB included demographic characteristics and comorbidities from the 12 months prior to the index date. Odds ratios (OR) and 95% confidence intervals (CI) were calculated from multivariable conditional logistic regression models to identify risk factors for bleeding.

Results:
Among 542 MB cases and 2,710 controls, MB cases were older and had more comorbidities (Table 1). Based on the multivariable modeling, increased age, anemia, prior gastrointestinal bleeding, heart failure, and vascular disease were identified as the strongest risk factors for MB (p<0.0001 for all).

Conclusions:
Several risk factors for MB were identified, although some findings may be affected by unmeasured confounding effects. These risk factors may assist in the development of clinical management strategies.
Abstract 17293: Human Leukocyte Antigen-G Polymorphisms Association to Post Heart Transplant Donor Specific Antibodies
Authors: Lazarte Julieta , Goldraich Livia , Manlhiot Cedric , Kawajiri Hiroyuki , Grosman-Rimon Liza , Ghashghai Arash , Rao Vivek , Delgado Diego
Published: July 2021

Introduction:
Human Leukocyte Antigen (HLA)-G is a natural immune regulator that inhibits T cells, NK cells and B cell activity. In the context of transplantation, less rejection and better graft outcomes are associated with higher serum levels of HLA-G. The association between HLA-G polymorphisms in the recipient and donor and post-transplant donor specific antibodies (DSA) has never been explored. DSA can lead to antibody-mediated rejection and are associated with worse outcomes. Objective: to determine the association between HLA-G single nucleotide polymorphisms (SNPs) in the recipient and donor and DSA.

Methods:
251 adult heart recipients and 196 matching donors were evaluated for various HLA-G SNPs. Serum from patient and donor were tested for positive presence of HLA Class I antibodies. DNA was genotyped for 14bp INDEL, G*01:01, G*01:04 and G*0:05N. The analysis was performed first in univariable regression models and then in multivariable regression model using a backward selection approach of potential risk factors with a univariable associations with p-value <0.10. The model automatically included time since transplantation as an obligatory covariate.

Results:
General characteristics: recipient age 48.2±12.1 years, 69% males and donor age 35.5±14.3 years. Of those, 19 (8%) had at least one positive DSA diagnosis. In a multivariable analysis adjusted for time since transplant, documented non-compliance and blood group A, the presence of donor G*01:04 allele was identified with a protective role for the development of DSA (0.079, CI 0.02-0.39, p= 0.002). Patient allele G*01:05N was associated with increased risk for DSA (12.95, CI 2.36-71.00, p= 0.003). Lastly, donor SNP 14bp (DEL vs INDEL/INS) was independently associated as a risk factor for DSA (5.75, CI 1.70-19.36, p= 0.005).

Conclusions:
Three SNPs from the donor and recipient were identified to influence the development of donor specific antibodies. This is the first study to investigate the association of HLA-G to the development of donor specific antibodies and to demonstrate both detrimental and beneficial roles for HLA-G polymorphisms.
Abstract 17300: Acute Kidney Injury is Associated With High Mortality in Patients With Atrial Fibrillation
Authors: Yedlapati Siva Harsha , Younus Usman , Stewart Scott H
Published: July 2021

Introduction:
The prevalence of atrial fibrillation (AF) is high in patients with chronic kidney disease (CKD). The mortality risk of AF in the presence of CKD is also significantly high. Multiple theories of which importantly, the renin-angiotensin-aldosterone system activation causing increased ventricular remodeling and heart failure, explain the increased incidence of AF in CKD. However, there are no data available on the effects of acute kidney injury (AKI) on mortality in patients with AF. We sought to investigate the prevalence and association of AKI with in-hospital mortality in patients presenting with AF.

Methods:
We performed a cross-sectional analysis of the 2011 Nationwide Inpatient Sample (NIS). Using logistic regression methods appropriate for the NIS sample design, we estimated the mortality risk associated with AKI in AF patients and evaluated factors that might modify this association.

Results:
In 2011, AF accounted for 457662 (1.4%) of overall adult admissions in the United States with an in-hospital mortality rate of 1%. Among these hospitalizations 30894 (6.8%) had a concomitant AKI diagnosis. The prevalence of AKI was higher (38%) in patients who died during these AF hospitalizations. The mortality risk in AF hospitalizations with an AKI diagnosis remained high even after adjusting for factors associated with AKI including age, sex, CKD, sepsis, hypertension, diabetes, congestive heart failure (CHF), smoking and heavy alcohol use (odds ratio 5.6; 95% CI (4.7 - 6.6); P<0.0001), relative to patients hospitalized with a non-AF diagnoses (odds ratio 3.3; 95% CI (3.2 - 3.4). The factors that interacted with AKI in predicting mortality risk in AF hospitalizations were underlying CKD, CHF, diabetes and alcoholism.

Conclusion:
Among hospitalized patients with AF, AKI is associated with significantly high mortality. This mortality was higher when compared to patients hospitalized with a non-AF diagnosis. Interpretation of our results must be conservative given the study design and data limitations. Future research using primary data sources might help identify factors associated with increased mortality in AKI patients presenting with AF.