bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 17224: Volatile Anesthetic Agents Increase Cerebral to Systemic Blood Flow Ratio in Children Undergoing Cardiac Magnetic Resonance Imaging
Authors: Buddhavarapu Amulya , Raga Luisa , Alanmanou Euleche , Porayette Prashob
Published: July 2021

Introduction:
Cardiac magnetic resonance imaging (CMR) can reliably assess hemodynamics in children. Anesthetic agents may affect cerebral blood flow (CBF) and change the cerebral to systemic perfusion ratio.

Hypothesis:
Volatile anesthetic agents cause significant cerebral vasodilation resulting in descending aorta (DAo) flow reversal.

Methods:
Blood flow was measured in patients who underwent cine phase contract velocity mapping during CMR (1.5T, Philips Ingenia, Amsterdam, The Netherlands) with or without general anesthesia (GA) at our institution. Patients with a known cause for flow reversal in DAo (e.g. aortic insufficiency, aorto-pulmonary shunt/collaterals) or brain pathology were excluded. Flows in superior vena cava (SVC, surrogate for CBF), ascending aorta (AAo, measure of cardiac output), and DAo (measure of lower body perfusion) were analyzed. Measures of central tendency, standard deviation, correlation coefficient and Student’s t-test were calculated. Variables including anesthetic agents, body surface area (BSA), mechanical ventilator parameters and vital signs were assessed.

Results:
A total of 93 CMR scans were performed with GA (n=43, age 3 m to 15 y, BSA 0.29-2.4 m
2
) or without GA (n=50, 2 w to 21 y, BSA 0.2-2.89 m
2
). There was significant flow reversal in DAo (mean 7.62% +/- SD 7%) in GA group using volatile agents compared to non-GA patients (1.16% +/- 1.78%; p-value <0.001). SVC flow was higher in GA (1.66+/-1.02 ml/min/m
2
) than non-GA patients (1.28+/-0.53 ml/min/m
2
) but did not reach statistical significance (p=0.06). GA group had significantly higher SVC (cerebral blood) to AAo flow (cardiac output) ratio (0.53 +/- 0.13) than non-GA group (0.44 +/- 0.17; p=0.003), probably from increased CBF from cerebral vasodilation by volatile anesthetic agents. Patients with BSA >1.2 m
2
and GA (0.84 +/- 0.27) had a tendency to have higher SVC/DAo flow ratio compared to non-GA (0.69 +/- 0.3; p = 0.06) patients. There was a positive correlation between the end tidal CO
2
and SVC flow (r 0.486, R
2
0.236).

Conclusions:
The flow rates of SVC, AAo and DAo using CMR must be interpreted with caution in children, taking into account the effects of GA on the cerebral and lower body perfusion. This difference may be relevant in patients with congenital heart disease, especially with cavo-pulmonary and Fontan circulation.
Abstract 17226: Increased Risk of Heart Failure Associated With Left Atrial Remodeling Without Known Atrial Fibrillation
Authors: Edwards Jodi , Fang Jiming , Healey Jeff S , Yip Kathy , Mielniczuk Lisa , Gladstone David J
Published: July 2021

Background:
Atrial fibrillation (AF) significantly increases risk for heart failure (HF) and independently increases mortality and adverse in-hospital outcomes in HF patients. Validated clinical risk scores (ARC2H) can predict HF in patients with AF, but are limited in application as AF is frequently clinically silent or undetected. However, AF may be preceded by significant preclinical remodeling (left atrial enlargement (LAE) or excessive atrial ectopy (EAE)). Whether LAE and EAE are associated with HF prior to AF is unclear.

Method(s):
We analyzed consecutive adults >65 years with outpatient echocardiography or Holter at 11 Ontario community cardiology clinics (2010-2017). Exclusions were history of AF, anticoagulation, pacemaker/ICD/ILR, and prosthetic valve. Using linked administrative databases, we assessed 5-year rates of HF (primary) and incident AF and death (secondary) associated with LAE and EAE and among subgroups (M vs. F; <75 vs. >75; CHADS-VASC 0-2 vs. 3-6). Competing risks cox proportional hazards estimated adjusted hazard of HF for severe LAE: >47mm (M);>52mm (F)) or increased APBs/hour (EAE: >30) or both LAE and EAE, adjusting for age, vascular comorbidities and left ventricular (LV) dysfunction.

Results:
In 28,261 adults (mean 73+/-6 years), direct age-adjusted survival was reduced for those with severe LAE and EAE. 5-year rates of HF were increased for severe (8.8%) vs. moderate (3.5%) and mild (1.4%) LAE and for those with excessive (3.8%) vs. normal (2.5%) ectopy. For both LAE and EAE, those >75 and with a CHADS score 3-6 showed marked increases in HF at 5 years compared to <75 (LAE: 10.6% vs. 7.9%; EAE: 4.3% vs. 1.9%) and CHADS score 0-2 (LAE:21.4% vs. 6.6%; EAE: 8.9% vs. 2.4%). Severe LAE increased hazard of HF 2-fold (HR=2.07; p<.0001), and incident AF over 3-fold (HR= 3.43; p<.0001) and EAE increased hazard of HF (HR=1.31; p<.0001) and incident AF (HR=1.13; p<.0001). Those with
both
LAE and EAE showed an over 3-fold increased hazard of HF (HR=3.28; p<.0014).

Conclusions:
Severe LAE and EAE without known AF are associated with increased risk of HF and AF after adjusting for LV dysfunction, particularly for those >75 and with high vascular burden. These data have implications for risk stratification, AF screening, and trials for HF prevention in individuals with left atrial remodeling.
Abstract 17231: Sodium Channel Blockers Shorten Prolonged QTC in Patients With Rett Syndrome
Authors: Nguyen Hoang H , John Somberg , Wilkie Mary , Jacobson Jessica , Jutzy Gregory , Buhrfiend Colleen , Heydemann Peter
Published: July 2021

Introduction:
Rett syndrome (RTT) is an X-linked disorder caused by mutations in the MECP2 gene resulting in various neurological, respiratory, and gastrointestinal symptoms. Up to 25% of deaths in RTT are sudden. Prolonged corrected QT (QTc) has also been reported and thought to be a cause of sudden death in RTT. Previous studies in mice with RTT showed that MECP2 mutations lead to persistent increased cardiac sodium current causing prolonged QTc and increasing risks of ventricular tachycardia. The aim of this study was to determine whether sodium channel blockers lidocaine (acutely) and mexiletine (chronically) shorten QTc in RTT patients.

Hypothesis:
Sodium channel blockers such as lidocaine (acutely) and mexiletine (chronically) significantly shorten QTc (≥ 30ms from baseline) in RTT patients with prolonged QTc.

Methods:
RTT patients with prolonged QTc were prospectively enrolled to receive a lidocaine attenuation test. The test consisted of a loading dose of 1 mg/kg intravenous lidocaine followed by a continuous infusion at 50 μg / (kg·min). Patients were deemed responders should their QTc shorten by 30 ms or more. These patients were then prescribed mexiletine for chronic therapy.

Results:
A total of 6 patients (all females) were given lidocaine and mexiletine. The median age of the cohort at the time of testing was 12 years (8-19 years), and the median QTc before therapy was 480.5 ms (476-506 ms). All 6 patients responded positively to lidocaine with median QTc shortening of 44.5 ms (33-54 ms,
P
= 0.018). The median daily dose of mexiletine was 8.75 mg/kg. The median duration of therapy was 5 months (4-12 months). Mexiletine shortened QTc by an average of 47 ms at latest follow-up (
P
= 0.016). One patient developed whole-body tremors as a side effect of mexiletine, which was stopped.

Conclusions:
Sodium channel blockers that target late sodium channels were effective in shortening QTc thereby confirming the presence of late sodium current causing prolonged QTc in RTT. Therefore mexiletine could be used clinically in RTT patients with long QTc. Larger and longer studies are needed to confirm these drugs’ positive effects in shortening the QTc and reducing arrhythmic events in RTT patients.
Abstract 17245: Deficiency of Tet Methylcytosine Dioxygenase 2 (tet2),A Key Enzyme in Cytosine Demethylation,Is an Epigenetic Driver of Inflammation and Disease Progression in Pulmonary Arterial Hypertension
Authors: Potus Francois , cook Elina K , Tian Lian , Hindmarch Charles C , Lima Patricia , Michael Rauh J , Archer Stephen L
Published: July 2021

Background:
Pulmonary arterial hypertension (PAH) is a lethal vasculopathy characterized by remodelling of distal pulmonary arteries associated with inflammation, endothelial cells (EC) dysfunction and a pro-proliferative/anti-apoptotic phenotype in pulmonary arterial smooth muscle cells (PASMC). Tet methylcytosine dioxygenase 2 (Tet2) is a key enzyme in cytosine demethylation that is crucial for epigenetic control of gene expression. Deficiency of Tet2 expression in myeloid cellsresults in increased inflammatory cytokine levels. Moreover, impaired Tet2 expression in EC has also been associated with decreased autophagy, as well as EC dysfunction. In addition, Tet2 silencing contributes to pro-proliferative phenotype of SMC. Thus, we hypothesized that Tet2 deletion would contribute to PAH by upregulation of inflammation and induction of PASMC proliferation and EC dysfunction.

Methods and Results:
To assess the ability of Tet2 deficiency to induce PAH we assessed cardiopulmonary hemodynamics in a conditional hematopoietic and endothelial cells Tet2
-/-
mouse model. Tet2
-/-
mice developed PAH associated with significant increases of right ventricular systolic pressure (RVSP), elevation of total pulmonary resistance (TPR) and increased vascular wall thickness of distal pulmonary arteries. Tet2
-/-
lung tissue as well as macrophages and EC sorted from the lung displayed aberrant inflammatory cytokine signalling with robust overexpression of IL1βnoted on a Nanostring immune gene expression panel. In vitro IL1βincreased PASMC proliferation measured using EDU. Downregulation of TET2 in PASMC using siRNA resulted in a similar PAH-like phenotype. Moreover, lung from Tet2
-/-
mice exhibited an alteration of vasoactive mediator gene expression (increased endothelin-1 (ET1), Arginase 2 (Arg2) and decreased eNOS). Finally we showed that downregulation of Tet2 (achieved by nebulization of si-Tet2) in rats with monocrotaline-induced PAH exacerbated disease severity (increasing TPR adverse pulmonary vascular remodelling).This phenotype was independent of the sex, was associated with a moderate decrease in RV function but had no significant effect on LV hemodynamic parameters.

Conclusions:
Tet2 is a protective epigenetic regulator that when conditionally downregulated in hematopoietic and endothelial cells leads toPAH by inducing a state of inflammation that contributes to PASMC proliferation and EC dysfunction which drives adverse pulmonary vascular remodelling.
Abstract 17249: Impacts of Isometric Handgrip Exercise and Post-Exercise Circulatory Arrest on Hemodynamics and Left Ventricular Function in Heart Failure With Preserved Ejection Fraction
Authors: Moriwaki Keishi , Fujimoto Naoki , Miyahara So , Fukuoka Shusuke , Ishiyama Masaki , Omori Taku , Sugiura Emiyo , Dohi Kaoru , Ito Masaaki
Published: July 2021

Introduction:
Isometric handgrip (IHG) training at 30% maximal voluntary contraction (MVC) lowers blood pressure (BP) in patients with hypertension and healthy individuals. However, impacts of IHG and post-exercise circulatory arrest (PECA), which isolates the metaboreflex control, on left ventricular (LV) function and hemodynamics have been unclear in patients with heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF).

Methods:
Sixteen patients with HF (age 63±13 years, 5M:11F, 10HFpEF:6HFrEF) underwent invasive LV pressure-volume assessments using conductance catheter with microtip-manometer during 3min of IHG exercise at 30% MVC, followed by 3 min of PECA. Impacts of IHG and PECA on LV function and hemodynamics were evaluated and compared between HFpEF and HFrEF.

Results:
During 3 min of IHG at 30% MCV, heart rate increased by 10±8 bpm in HFpEF and by 14±6 bpm in HFrEF. IHG elevated LV end-systolic BP in both HFpEF (134±21 vs. 158±30 mmHg, p<0.01) and HFrEF (119±30 vs. 142±31 mmHg, p<0.01) with no change in stroke volume. There was a trend towards an increase in LV end-diastolic pressure in both groups (HFpEF:14±5 vs. 19±10 mmHg, HFrEF: 15±12 vs. 23±11 mmHg). Time constant of LV relaxation was unchanged by 3 min of IHG in HFpEF (52±14 vs. 54±15 ms), while it was prolonged in HFrEF (48±7 vs. 60±9 ms, p<0.01, groupхtime interaction effect p=0.08). During PECA, LV end-systolic BP decreased in both groups and was maintained higher than baseline throughout PECA only in HFpEF.

Conclusions:
Although IHG exercise at 30% MVC for 3 min would elevate LV end-systolic and end-diastolic pressures, this IHG exercise has no detrimental effect on LV systolic and diastolic function, especially in HFpEF patients. Chronic effect of IHG training on BP and hemodynamics will need to be evaluated in HFpEF patients who often suffer from arterial hypertension.
Abstract 17257: Does Repeat Imaging Validate Visual Coronary Artery Calcium Scoring on Non-Electrocardiogram Gated Chest Computed Tomography?
Authors: Koop Hans , Kirsch Jacobo , Berman Kelsey , Martinez Felipe
Published: July 2021

Aim:
To investigate if estimation of the amount of calcium in the coronary system utilizing a visual coronary artery calcium scoring (CACS) system (Kirsch et al. Detection of coronary calcium during standard chest computed tomography correlates with multi-detector computed tomography coronary artery calcium score) in non - electrocardiogram (ECG) gated chest computed tomography (CT) scans maintains its strong correlation with the Agatston CACS on dedicated ECG gated cardiac CT exams across two or more points in time per patient.

Methods:
A visual scoring system (Weston score, WCS) was previously developed assigning a score (0-3, total score 0-12) for each coronary vessel including the left main trunk. Predetermined score cutoffs in both Agatston and Weston scoring methods were designated for risk stratification. Following institutional review board approval, we retrospectively analyzed 127 total body CT scans on 53 low-risk patients referred by executive health who had received repeat CT scans between 2007 and 2018 and compared the traditional Agatston CACS with the Weston score. Analysis: The data were gathered from a total of 53 executive health patients ages 33 to 71, with an average age of 51. 83.6% were male and 16.4% were female. 118 scans were examined, taken between 307 and 2,792 days apart, with an average of 937 days between scans. The Weston and Agatston scores predicted the same risk classification for 79.7% of the first set of scans, with 10.2% uprisked and 10.2% downrisked by their Weston scores. For the second set of scans, 78.0% had the same classification, with 10.2% uprisked and 11.9% downrisked by their Weston scores. Weston scores predicted 100% of scans within one risk classification of the corresponding Agatston score across all pairs of scans.The average CACS utilizing the Agatston scoring method was 54.3, with a standard deviation of 148.6 due to a large positive skew in the data. The corresponding Weston scores had an average of 1.1, with a standard deviation of 2.14.

Conclusion:
A visual CACS system (WCS) performed on non-gated CT scans allows risk stratification for cardiac events in a similar manner as the Agatston CACS on ECG-gated CT scans even at separate points in time.
Abstract 17264: Impaired Right Ventricular and Pulmonary Vascular Function in a Mouse Model of Sickle Cell Disease
Authors: Schreier David A , Tabima Diana M , Philip Jennifer L , Hacker Timothy A , Chesler Naomi C
Published: July 2021

Introduction:
In sickle cell disease (SCD), red blood cell abnormalities contribute to pulmonary hypertension (PH) in adults and children. Right ventricular (RV) hypertrophy and dilatation are also associated with SCD, likely due to a combination of PH and coronary microvascular disease. The goal of this study was to use a comprehensive hemodynamic approach to quantify the impact of SCD on RV function, RV afterload, and cardiopulmonary reserve.

Hypothesis:
We hypothesized that mice with SCD would have poor RV function, increased RV afterload, and less cardiopulmonary reserve compared to mice without SCD.

Methods:
22 male Berkeley SCD mice and 24 male C57Bl6 mice (CTL) aged 30-32 weeks old were used. Approximately half of each genotype were used for RV function and VVC measurements; RV pressure-volume (PV) loops were obtained at baseline and after a brief inferior vena cava occlusion in an open-chest procedure. In the rest, RV afterload was quantified from simultaneous pulmonary artery pressure and diameter measurements in a closed-chest procedure. All measurements were obtained under normoxic ventilation (21% oxygen) and, subsequently, after acutely hypoxic (AH) ventilation (10% oxygen) to assess cardiopulmonary reserve.

Results:
RV hypertrophy and increased RV systolic pressure confirmed PH in SCD mice (Figure A). Cardiac output, RV end-diastolic volume, and preload-recruitable stroke work (PRSW) were increased in SCD mice and RV compliance was decreased compared to controls. In response to AH, cardiac output dropped dramatically (Figure B), PRSW decreased, pulmonary vascular resistance increased and compliance decreased more in SCD mice than in CTL mice, indicating decreased cardiopulmonary reserve in SCD mice.

Conclusions:
SCD mice demonstrate PH, compromised RV function and impaired cardiopulmonary reserve, which mimics clinical cardiopulmonary consequences of SCD and suggests that these mice are a useful tool to investigate mechanical mechanisms of cardiopulmonary progression in SCD.
Abstract 17275: Evaluating the Convergent and Discriminant Validity of Four Frailty Instruments in Adults With Heart Failure: Results From the Frame-HF Study
Authors: McDonagh Julee , Salamonson Yenna , Prichard Roslyn , Jha Sunita R , Ferguson Caleb , Macdonald Peter S , Davidson Patricia M , Newton Phillip J
Published: July 2021

Introduction:
Frailty assessment has become increasingly common in those with heart failure. The most frequently used frailty instrument is the Frailty Phenotype (FP). The validity of this instrument in those with heart failure is yet to be determined.

Aim:
To examine the convergent and discriminant validity of four frailty instruments: i) the FP ii) a Questionnaire-only version of FP [q-FP]; iii) St. Vincent’s Frailty [SVF]; and iv) the Frailty Instrument for Primary Care of the Survey of Health, Ageing and Retirement in Europe [SHARE-FI] for assessing the frailty status of adults with heart failure.

Methods:
Using a cross-sectional survey design, individuals aged ≥ 18 years, diagnosed with heart failure were recruited from the inpatient cardiology ward and outpatient heart failure clinic of a metropolitan academic hospital. In addition to assessing all items of the frailty instruments, other data collected included: a) NYHA classification; b) quality of life and health status using the EQ-5D-5L; c) physical status using the Australian-modified Karnofsky Performance Scale (AKPS); and d) 10-item Depression in Medically Ill (DMI) measure.

Results:
A total of 131 participants were recruited and included in the analyses, there were wide variations in frailty status across the four frailty instruments (Figure 1). Inter-correlations were highest between SVF and SHARE-FI instruments (
r
= 0.62). The NYHA classification were correlated with SVF (
r
= 0.46) and SHARE-FI (
r
= 0.42). Similarly, all EQ-5D-5L dimensions were correlated with both SVF and SHARE-FI but not with FP or q-FP. The SVF differentiated between high and low AKPS scores (χ
2
= 11.70,
df
: 2,
p
= 0.003) and DMI scores (χ
2
= 7.28,
df
: 2,
p
= 0.026). Similarly, the SHARE-FI also had good discriminant validity using AKPS scores (χ
2
= 9.25,
df
: 2,
p
= 0.010) and DMI scores (χ
2
= 14.32,
df
: 2,
p
= 0.001).

Conclusions:
The SVF and SHARE-FI demonstrated good convergent and discriminant validity. Both instruments provide a valid alternative to the FP for the assessment of frailty in those with heart failure.

Figure 1: Classification of frailty categories: FP, Questionnaire-only FP, SVF and SHARE-FI
Abstract 17276: Tissue Plasminogen Activator Loaded Microbubbles for the Treatment of Coronary Microvascular Obstruction
Authors: D’Auria Stephen J , Istvanic Filip , Yu Francois , Chen Xucai , Pacella John
Published: July 2021

Introduction:
Microvascular obstruction (MVO) occurs frequently during successful PCI for acute myocardial infarction. Our previous work has demonstrated the potential of using ultrasound targeted microbubbles (MBs) cavitation to relieve MVO, termed sonoreperfusion (SRP).

Hypothesis:
In the present study, we aim to develop a tPA loaded MB in order to utilize the thrombolytic effects of locally delivered tPA to enhance SRP, with a decreased tPA dose to limit the bleeding risk.

Methods:
tPA (1 mg/mL) was first modified via a maleimide linkage using BMCC-biotin, leading to a biotinylated protein. The biotinylated tPA (0.87 mg/mL) was then mixed with streptavidin labeled lipid shelled MB (1х10^9MB/mL) via biotin-streptavidin bridging. The enzymatic activity of the tPA in these tPA loaded MBs were was tested with whole porcine blood thrombus and with a tPA chromogenic activity kit. The loading capability of tPA onto the MBs was determined by BCA protein assay. The SRP efficacy of the loaded tPA MB was tested in an in vitro model of MVO and compared with full dose systemic tPA as well as modified MB.

Results:
tPA loaded MB showed successful lysis of whole porcine blood clot
in vitro
, as evidenced by decreased thrombus weight. Subsequent analysis of tPA activity showed that there was no significant difference in the activity of stock tPA when compared to the BMCC labeled tPA (42.0±3.4 IU vs 44.7±1.1 IU,
p
=0. 17). tPA was loaded onto MB at volumetric ratios of 3 units of tPA at 0.87 mg/mL to 1 unit (3:1) of MB at 1e9 MB/mL (43.5±2.2 IU,
p
=0.38) and 6:1 (39.3±1.5 IU,
p
=0.15). There was decreased activity in the 1:1 group. The loading capability of tPA for the 3:1 tPA loaded MB was 6.2e-7 μg per MB, with a loading efficiency of 10.4% of the stock tPA. Early
in vitro
work showed the tPA loaded MB to be non-inferior at relieving MVO with SRP when compared to infusion of full dose tPA and SRP with standard unmodified tPA.

Conclusions:
We successfully loaded tPA onto the surface of a lipid encapsulated MB, with retention of the enzymatic activity of tPA. The loading efficiency was 10.4% of the stock tPA. The tPA loaded MB demonstrated similar reperfusion efficacy to full systemic dose tPA. Thus, this approach of targeted local delivery of tPA may provide a means to mitigate bleeding risk without sacrificing drug efficacy.
Abstract 17299: AF Drivers Where Ablation Terminates Persistent AF Fluctuate Due to Competing Drivers but Remain Anchored in Specific Locations
Authors: Meckler Gabriela L , Kowalewski Christopher A , Rogers Albert J , Rodrigo Miguel , Clopton Paul , Shenasa Fatemah , Alhusseini Mahmood I , Swerdlow Mark , Joshi Vijay , Hossainy Samir , Zaman Junaid , Baykaner Tina , Brachmann Johannes , Miller John , Krummen David E , Sauer William , Viswanathan Mohan , Wang Paul , Narayan Sanjiv M
Published: July 2021

Introduction:
Mechanisms for persistent atrial fibrillation (AF) are unclear. We reasoned that AF drivers may fluctuate due to competing drivers in stereotypical spatial locations. This may explain why studies focused on small regions may show disordered waves while global mapping shows organized drivers.

Hypothesis:
That closely-spaced AF drivers may fluctuate more than drivers that are widely separated by mapping AF globally for prolonged durations using 2 independent mapping methods.

Methods:
In 55 patients with non-paroxysmal AF (24% female; 62.2±9.7 years), ablation at drivers identified by 64 pole baskets (Abbott, CA) terminated AF before pulmonary vein (PV) isolation. We mapped 360±45 AF cycles using (1) an open source phase method and (2) commercial tools, and quantified both fluctuations and locations of mapped drivers.

Results:
Patients had 4.2 ± 2.0 potential drivers by non-proprietary mapping (fig A), located per fig B. AF termination sites showed rotational/focal patterns (51/55 vs 55/55 patients; p=0.13 methods 1 vs 2) that fluctuated over time. In space, each AF driver was most prevalent in the left atrium, with clustering near left PVs (p<0.05). Separation between drivers varied non-significantly with fluctuations. Drivers trended to be more stable in LA than RA (χ
2
= 2.11, p=0.12).

Conclusions:
Potential AF drivers where ablation terminates persistent AF are spatially stable but fluctuate over time. Fluctuations reflected competing sources, trended to be more prevalent in left atrium but were not clearly related to inter-site distance. Studies should examine the functional determinants of AF driver fluctuations.
Abstract 17303: Permanent Cardiac Pacemaker Implant Improves Sleep Habit
Authors: Kattel Sharma , Hiki Masaru , Kasai Takatoshi , Saito Yuji , Daida Hiroyuki
Published: July 2021

Background:
Permanent cardiac pacemaker is indicated in patients with symptomatic bradycardia. Its role in sleep disorder is unknown, however some patient report improvement in their sleep habit after permanent cardiac pacemaker implant. We examined the role of permanent cardiac pacemaker in relation to patients’ sleeping habits.

Methods:
Total of 174 patients who agreed to participate in the study were included (21 Implantable Cardioverter Defibrillator (ICD) and 153 pacemaker implants). The ICD group was used as the control group. Patients with bi-ventricular pacemaker implants for cardiac re-synchronization therapy were excluded from the study. Questionnaires about the sleep habit were evaluated before and after the device implant and analyzed using paired T test and Chi square test.

Results:
The indications for permanent pacemaker therapy were high grade AV block (33%), sick sinus syndrome (64%) and syncope (1%). Indications of ICD were primary or secondary sudden cardiac death prevention without history of known symptomatic bradycardia (100%). Mean Ventricular pacing was 40.39% (interquartile range: 97%) of the time in the pacemaker group. There were no baseline differences in sleep duration and quality of sleep in both the ICD and pacemaker group prior to device implant. Improved sleep habit (46% in pacemaker vs 23% in the ICD group, P=0.04) and better quality of sleep (44% in pacemaker vs 19% in ICD, P=0.01) were reported after device implant. The patients in pacemaker group reported much improvement in sleep duration (average by 30 minutes in Pacemaker vs 15 minutes in ICD, P=0.002).

Conclusions:
Patients who had permanent pacemaker implant for symptomatic bradycardia showed improved sleep quality and duration than the patients with ICD implant for primary or secondary sudden cardiac death prevention. Mechanisms of improved sleep habit in pacemaker group are unclear, but possibly associated with improved cardiac output with consistent heat rate during sleep from the pacemaker. Further large-scale studies are needed to validate this concept.
Abstract 17304: Brief Exposures to Air Pollutants Dysregulates
PCK1
Expression, Carbohydrate and Lipid Metabolism in
ApoE
Knockout Mice
Authors: Gupta Rajat , Ramanathan Gajalakshmi , Zhao Yuki , Yin Fen , Ricks Jerry , Rosenfeld Michael E , Yang Xia , Araujo Jesus A
Published: July 2021

Introduction:
Previous animal studies have shown that long exposures to particulate matter (PM) and diesel exhaust particles (DEP) promote atherosclerosis. Air pollutants are also reported to cause nonalcoholic steatohepatitis (NASH), liver fibrosis and insulin resistance in animals exposed to PM<2.5 μm. We hypothesized that even brief exposures to air pollutants may alter metabolic pathways that could be responsible for vascular and liver diseases.

Methods:
ApoE
null mice were briefly exposed to diesel exhaust (DE) or filtered air (FA) to assess liver content of lipids, lipid and carbohydrate metabolism. Illumina microarrays and metabolomic analysis were performed in liver tissue. Transcriptomic data was analyzed using the Illumina Beadstudio software. Gluconeogenesis and glycogenolysis were evaluated in HepG2 cells after treatment with diesel exhaust particles (DEP). Gene expression was determined by qPCR.

Results:
DE exposures led to a significant increase in both liver triglyceride (Mean ± SEM, FA: 0.16 ± 0.01 vs DE: 0.22 ± 0.02 mg/mg protein, n=7, p=0.02) and cholesterol (FA: 15.53 ± 1.53 vs DE: 23.26 ± 2.16 μg/mg protein, n=5, p=0.02) content in
ApoE
null mice. Microarray analysis depicted a dysregulation of 477 genes, and metabolomic analysis identified 70 metabolites significantly upregulated in the DE group while 48 metabolites were downregulated. Interestingly, metabolites in the citric acid cycle demonstrated significant changes after DE exposure likely due to mitochondrial dysfunction. Key driver analysis revealed
Pck1
as a key driver gene. In-vitro experiments in HepG2 cells treated with DEP exhibited a significant upregulation in
PCK1
mRNA expression (DEP: 7.31 ± 0.2 vs control: 1.07 ± 0.07, n=3, p<0.01). Although treatment with DEP substantially depleted glycogen content as seen by periodic acid-schiff stain in cells, it significantly enhanced gluconeogenesis (DEP: 23.3 ± 1.2 vs control: 5.5 ± 0.6 μg/ml/mg protein, n=5, p<0.001), effects that were inhibited in the presence of a metabolic inhibitor of PCK1: 3-Mercaptopicolinic acid (3-MPA) (DEP: 23.28 ± 1.18 vs DEP + 3-MPA: 16.04 ± 1.16 μg/ml/mg protein, n=5, p=0.002) indicating that DEP-induced glucose production was due to increased gluconeogenesis.

Conclusion:
Exposure to diesel exhaust leads to multiple alterations in carbohydrate and lipid metabolism including increased glycogenolysis, gluconeogenesis and
PCK1
upregulation.
Abstract 17326: The Effect of Maintenance of Antegrade Pulmonary Blood Flow Upon Bidirectional Glenn on Pre- and Post-Fontan Outcomes
Authors: Baek Jae Suk , Park Chun Soo , Choi Eun Seok , Kwon Bo Sang , Yun Tae-Jin , Yu Jeong Jin , Kim Young-Hwue , Ko Jae-kon
Published: July 2021

Introduction:
Maintaining pulsatility at the time of bidirectional Glenn (BDG) has theoretical advantages and disadvantages. The practice is diverse throughout the centers and individual surgeons without clear rationale behind its application. We sought to investigate the impact of antegrade pulmonary blood flow on pre- and post-Fontan outcomes.

Methods:
From 2003 through June 2014, among 237 patients who underwent BDG as an interim palliation for functional single ventricle (FSV), patients with preexisting pulmonary blood flow from the ventricle before BDG were included and patients undergoing Kawashima operation or having history of Norwood operation or bilateral pulmonary arterial band were excluded (n=151). Patients were grouped by their presence or absence of antegrade pulmonary blood flow following BDG: group 1 (pulsatile) (n=73) or group 2 (non-pulsatile) (n=78). The pre- and post-Fontan outcomes were compared between two groups.

Results:
Age and weight at BDG were 7 months and 7.8kg. Oxygen saturation was higher in group 1 (84±4%) compared to group 2 (82±4%) before Fontan (p<0.001). The level of brain natriuretic peptide (BNP) was similar before Fontan (p=0.966). In pre-Fontan cardiac catheterization, mean pulmonary arterial pressure was similar (Group 1: 11±4mmHg vs. Group 2: 10±4mmHg, p=0.146), McGoon ratio seemed higher in group 1(2.6±0.6) compared to group 2(2.3±0.4) (p=0.057), and pulmonary vascular resistance was lower in group 1(1.3±0.7) compared to group 2(1.6±0.7)(p=0.038). A total of 136 patients (90%) underwent Fontan operation. Duration of stay in the intensive care unit (p=0.766), stay in hospital (p=0.142), and indwelling chest tube (p=0.128) was not different between groups. Overall survival after BDG was better in group 2 (p=0.046) [Figure]. In multivariable analysis, maintenance of pulsatility was identified as a risk factor for survival after BDG (p=0.012, HR 4.1 [CI 1.4-12.4]).

Conclusions:
Maintaining pulsatility at the time of BDG in FSV might be beneficial for pulmonary arterial growth and oxygen saturation without increasing BNP. However, such beneficial effect did not have a positive effect on subsequent Fontan outcome. Attention must be paid to the negative effect of pulsatility on overall post-BDG survival.
Abstract 17339: Maternal Predictors of Disparate Outcomes in Children With Single Ventricle Congenital Heart Disease
Authors: Asrani Priyanka , Pinto Nelangi , Puchalski Michael , Ou Zhining , Heuser Cara , Gibbins Karen , Silver Robert , Zinkhan Erin , Nance Amy , Miller Thomas
Published: July 2021

Introduction:
Significant variability in morbidity and mortality persists for children with single ventricle congenital heart disease (SV-CHD) despite standardization in medical and surgical care. Multiple risk factors for poor outcomes have been described, but they only explain a fraction of the disparity in outcomes. The Developmental Origins of Health and Disease (DOHaD) theory proposes that fetal adaptation to an adverse in utero environment alters the ability to respond to post-natal stressors and may explain additional risk for poor outcomes. This study assessed maternal risk factor association with disparate outcomes following SV palliation.

Hypothesis:
Maternal factors related to weight, diabetes, hypertension, and smoking may be associated with an increased risk of poor outcomes in children with SV-CHD.

Methods:
This retrospective observational cohort study included all term maternal-infant pairs with a diagnosis of SV-CHD who underwent surgical palliation from 2006-2015 at Primary Children’s Hospital. Pairs lacking maternal variables of interest or infant follow-up data up to 1 year were excluded. The association of death or transplant with maternal risk factors [abnormal pre-pregnancy BMI, abnormal weight gain during pregnancy (≤ 7 kg or ≥ 20 kg), any type of hypertension or diabetes and smoking] was analyzed using a multivariable logistic regression model.

Results:
Of 190 infants who qualified, 135 (71%) maternal-infant dyads had complete data for inclusion. Systemic right ventricular morphology was present in 69% and 31% had systemic left ventricular morphology. Death or transplant occurred in 48 infants (36%) during an average follow-up of 2.2 years (0.1-11.7 years). Abnormal weight gain during pregnancy was present in 34 (25%) mothers, of which 24 had excessive (>20 kg) and 10 had inadequate (<7 kg) weight gain. Prevalence of other risk factors was 53% with an abnormal pre-pregnancy BMI, 10% for diabetes, 6% for hypertension and 8% for smoking. Abnormal weight gain during pregnancy was associated with an increased risk of death or transplant in offspring with SV-CHD. (OR=2.55, 95%CI:1.11-5.84, p=0.027).

Conclusions:
Abnormal maternal weight gain (excessive or inadequate) during pregnancy is a novel risk factor that may contribute to worse outcomes in SV-CHD.
Abstract 17340: Disparities in Wait Times for Heart Transplant by Racial and Ethnic Minorities
Authors: Lala Anuradha , Ferket Bart S , Rowland John , Pagani Francis D , Gelijns Annetine C , Moskowitz Alan J , Horowitz Carol R , Pinney Sean P , Bagiella Emilia , Mancini Donna M
Published: July 2021

Introduction:
Although wait times vary widely across geographic regions and blood type under the current allocation system, it is unclear if minority patients have longer waitlist times.

Hypothesis:
We hypothesized that racial/ethnic minority patients experience longer wait times to transplant, even after accounting for age, gender, blood type, heart failure severity defined by UNOS status, and region.

Methods:
Patients listed for first transplant from 2005-2016 in the UNOS database were analyzed by racial/ethnic groups: African-American (AA), Hispanic, White (Non-Hispanic) and Other. We estimated median time to transplant for each group by year of listing using cumulative incidence functions and accounted for competing risks of waitlist mortality and delisting. For 2015-2016, we performed multivariable cause-specific Cox regression modeling accounting for age, gender, UNOS status urgency (status 1A, 1B, 2, 7) ABO blood type, and region by organ procurement organization. The reference population was Whites.

Results:
A total of 36,801 patients (21.5% AA, 7.8% Hispanic, 4.0% Other and 66.6% White) were available for analysis. Since 2005, the proportion of AAs on the waitlist has increased slightly, while the proportion of Whites has decreased. Wait times increased to a peak in 2014 for all ethnic/racial groups, but were disproportionally increased for AAs. In 2015-2016 this disparity persisted but was less pronounced compared to prior years. (
Figure
) After multivariable adjustment, the Hazard Ratio for time to transplant in AAs was 0.90 (95% CI 0.83 – 0.96) compared to Whites, with no prolonged time to transplant for other minorities.

Conclusions:
AAs experience disproportionally long wait times for heart transplant, which could not be explained by traditional determinants of time to transplant. How the new allocation system implemented in 2018 will impact this disparity should be a focus for ongoing population health research.
Abstract 17355: Anti-Inflammatory Nanotherapy Alters Immune Cell Composition and Reduces Lesion Area of Atherosclerotic Plaques in Ldlr-/- Mice
Authors: Allen Sean D , Liu Yu-Gang , Scott Evan A
Published: July 2021

Introduction:
Atherosclerosis is a multi-stage disorder with an inflammatory immune component. We hypothesized that the targeted delivery of an anti-inflammatory small molecule to macrophages could modulate immune cells in the plaque and potentially reduce plaque progression. We employed celastrol as an inhibitor of NF-kB and used poly(ethylene glycol)-block-poly(propylene sulfide) (PEG-bl-PPS) polymeric micelles (MCs) for controlled delivery.

Methods:
PEG-bl-PPS polymer was formulated into nanocarriers at a concentration of 15 mg/mL in 1xPBS, with or without 100 ng of celastrol (Cel-MC or Blank MC). Ldlr-/- mice were fed a high fat diet for 3 months prior to the beginning of nanocarrier treatment. 100 μL of each MC formulation was administered to mice via tail vein injection once per week for 12 weeks.

Results:
Cel-MC inhibited NF-kB at lower concentrations compared to free celastrol
(Fig. 1a)
.
In vivo
, Cel-MCs significantly decreased neutrophils and NK cells in the aortas of atherosclerotic mice compared to blank MC controls
(Fig. 1b)
. Cel-MCs reduced the plaque lesion area, as determined by Oil Red O staining of aorta histology sections
(Fig. 1c)
.

Figure 1. Cel-MC treatment of atherosclerosis.
(a) NF-kB inhibition and cell viability using RAW Blue cells, error bars = S.D., n = 4. (b) Heatmap of percent change in cell populations based on flow analysis of ldlr-/- mice after 12 weeks of Cel-MC treatment, compared to blank MC treatment, n=6/4 respectively. (c) Oil Red O staining fluorescence area of aorta histology slides, n=4 mice, 3-4 sections per mouse. P-value determined using Welch’s t test.

Conclusions:
Cel-MC reduced NF-kB signaling
in vitro
and reduced immune cells in the aorta
in vivo.
The treatment course was well-tolerated by the mice and resulted in a significant reduction in plaque lesion area. These results demonstrate both the utility of targeted modulation of immune cells contributing to vascular inflammation.
Abstract 17373: Prescription Patterns and Outcomes of Direct Oral Anticoagulants and Warfarin in Patients With Atrial Fibrillation a Real World Analysis
Authors: Kattoor Ajoe J , Pothineni Naga venkata K , Kovelamudi Swathi , Abraham Annette , Paydak Hakan , Mehta Jawahar L
Published: July 2021

Introduction:
Direct Oral Anticoagulants (DOACs) are used for stroke prevention in Atrial Fibrillation (AF).

Hypothesis:
We sought to evaluate differences in prescription patterns of DOACs and warfarin in new onset AF patients in relation to CHA2DS2Vasc score and compare outcomes of ischemic stroke, gastrointestinal (GI) bleed and intracranial hemorrhage (ICH) between DOACs and warfarin.

Methods:
All patients with a new diagnosis of AF from 2014 to 2017 were identified from the admission database at the University of Arkansas for Medical Sciences, AR, U.S.A. Trends in anticoagulant prescription were plotted in relation to CHA2DS2Vasc score. Baseline characteristics were compared using t-test and chi-square test as appropriate. Multivariate logistic regression was used to identify independent predictors of clinical outcomes of interest.

Results:
We examined a total of 2362 patients (1306 on warfarin and 1056 on DOACs). Prescription rates of warfarin increased with increasing CHA2DS2Vasc (Fig 1). Patients on warfarin had a higher prevalence of hypertension, diabetes, heart failure, renal failure and liver disease (Table 1a). On multivariate analysis, there was no difference in the incidence of ischemic stroke and GI bleeding between warfarin and DOACs (Table 1b). However, there was a trend towards lower incidence of ICH in DOAC group (p=0.06), despite wider usage in patients with higher CHA2DS2Vasc score.

Conclusions:
In a real-world setting, the use of DOACs was lower in patients with high CHA2DS2Vasc score compared with warfarin. Trend towards lower incidence of ICH was present in DOAC group. Further larger studies assessing safety of DOACs in patients with high CHA2DS2Vasc are needed.
Abstract 17385: Endothelium Specific Reduction in Mitochondrial ROS Reverses the Deleterious Effects on Coronary Endothelium Caused by Prolonged Increase in NADPH Oxidase Derived ROS
Authors: McCormack Isabella , Colantuono Bonnie , Stanley Melissa , Sellke Frank , Abid Ruhul
Published: July 2021

Introduction:
Recent findings from our lab demnstrated that prolonged increase in NADPH oxidase (NOX)-derived ROS results in increased mitochondrial (mito) ROS levels, reduced aspartate/dNTP synthesis, reduced coronary endothelial cell (EC) proliferation, and decreased recovery of post-MI cardiac function.

Hypothesis:
We hypothesized that endothelium-specific reduction in mitochondrial ROS will reverse the deleterious effects of prolonged NOX-ROS increase by improving mitochondrial function and aspartate/dNTP synthesis.

Methods:
Tetracycline (Tet)-ON/Tet-OFF binary transgenic mice, Tet-Nox2:VE-Cad-tTA
(NOX-OE),
were used as a model for endothelium-specific increase in the expression of the catalytic subunit of NADPH oxidase resulting in increased ROS. Mouse heart EC (MHEC) were isolated from Tet-ON and Tet-OFF Tg-Nox2 mice that were exposed to >16 weeks of increased EC-ROS. MHECs were then subject to mitochondrial antioxidants nitroxide (XJB-131) and nanoparticle (CeTiO2) followed by determination of mito-ROS, aspartate/dNTP synthesis, and EC proliferation. NOX-OE was crossbred with SOD-OE to generate a double-transgenic mice with EC-specific overexpression of mitochondrial antioxidant MnSOD (Sod2), Tet-Sod2:Tet-Nox2:VE-Cad-tTA (
SOD-OE
). Both NOX-OE and SOD-OE were subject to myocardial infarction (MI) LAD ligation experiments.

Results:
Mito-ROS levels were significantly reduced (by >2-fold) in MHEC from SOD-OE compared to NOX-OE. Both dNTP and proliferation were increased in SOD-OE, and also in NOX-EC treated with XJB-131 and CeTiO2. Together, these data suggest that reduction in mito-ROS abrogated negative effects of NOX-ROS in EC. Preliminary data demonstrate that there was an increase in capillary density (by 34± 5.8 %; p<0.05) and angiogenesis (by 2-fold) in SOD-OE post-MI myocardium compared to that of NOX-OE. Infarct sizes and cardiac function between NOX-OE and SOD-OE will be presented.

Conclusion:
These results suggest that reduction in mito-ROS can abrogate deleterious effects coronary endothelium caused by prolonged exposure to NOX-ROS. EC-specific modulation of mito-ROS may thus help develop therapeutic modalities to improve cardiovascular health and myocardial preservation in the post-MI heart.
Abstract 17389: The Role of Arterial Stiffness in Mediating the Association Between Grip Strength and Cardiovascular Events: The Korean Genome and Epidemiology Study
Authors: Choi Cheol Ung , Kim Woohyeun , Shin Chol , Choi Jong-il , Kim Seong Hwan , Seo Hong Seog , Park Chang Gyu , Rha Seung-Woon , Kim Eung Ju , Na Jin Oh , Kim Jin Won , Suh Soon Young , Jang Won Young , Park Yoonjee , Park Eun Jin , Kang Dong Oh
Published: July 2021

Introduction:
Grip strength has been associated with cardiovascular events. However, there have been no exact mechanisms explaining the association between grip strength and cardiovascular events.

Hypothesis:
The aim of this study was to assess whether arterial stiffness or endothelial function could mediate the association between grip strength and cardiovascular events.

Methods:
We studied 1508 participants (Age; 60 ± 7, Men; 47.5 %) from the Ansan cohort of the Korean Genome Epidemiology Study. Participants were assessed for grip strength, measured using a Jamar dynamometer. The central blood pressure, the augmentation index, and the pulse wave velocity were evaluated by using an applanation tonometer. Intima medial thickness was measured by B-mode ultrasonogram with a 7.5 MHz linear array transducer.

Results:
With increasing the grip strength, augmentation index decreased (r= -0.445, p<0.001). Pulse wave velocity (r= -0.044, p=0.109) and carotid intima medial thickness (r= -0.004, p=0.881) had no significant correlation with grip strength.

Conclusions:
Grip strength was inversely correlated with augmentation index. This result suggests that systemic arterial stiffness could mediate the association between grip strength and cardiovascular events.
Abstract 17406: Early Experience With Ultrasound Guided Distal Trans-Radial Access in the Anatomical Snuffbox in Coronary Angiography and Intervention
Authors: Lee Sangyeub , Yoon Woong-su , Bae Daehwan , Kim Min , Kim Sang Min , Bae Jang-Whan , Hwang Kyung-Kuk , Cho Myeong-Chan
Published: July 2021

Early experience with ultrasound guided distal trans-radial access in the anatomical snuffbox in coronary angiography and intervention.

Objective:
We aimed to demonstrate the feasibility and safety of the ultrasound guided distal trans-radial coronary angiography and intervention.

Methods:
Patients assigned to one operator program underwent diagnostic or procedural intervention through distal trans-radial approach in the anatomical snuffbox between January 2018 and May 2018. All of patients had palpable artery in their distal radial artery. The operator did the coronary procedure via distal radial access at anatomical snuffbox. When the pulse was weak or the target artery was very small, the operator punctured under ultrasound guidance (V-scan with dual probe, GE heathcare, USA)

Results:
56 patients were enrolled. Mean age of patients was 65.1 years old and 68% were male. About 70% of patients were presented with stable angina feature. In diagnostic procedure, 4F (3, 5.6%) or 5F (29, 54.7%) sheath was used and we did coronary intervention via 6F (21, 39.6%) Sheath. Ultrasound guided puncture was done for 33 patients (58.9%). Overall Success rate of distal trans-radial angiography and intervention was 94.6% (3 failed cases). Success rate of ultrasound guided procedure was 97% (only 1 failed case). Left distal radial puncture was done for 18 patients (33.9%). 16% of patients had chronic kidney disease, especially end stage renal disease (11%) to preserve radial artery which was potential candidate of arteriovenous fistulae for dialysis. There was no BARC type 2-5 bleeding in hospital stay and follow up at out-patient clinic.

Conclusion:
Ultra sound guided distal radial approach is feasible and safe as a good alternative technique for coronary angiography and interventions.