bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 15457: Novel Three-dimensional Principal Strain Analysis for Global Function of Right Ventricle After Repair of Tetralogy of Fallot. Can It Predict Need for Pulmonary Valve Replacement?
Authors: Matsubara Daisuke , Satriano Alessandro , Fine Nowell M , White James A , Pedrizzetti Gianni , Banerjee Anirban
Published: November 2020

Introduction:
Principal strain analysis (PSA) quantifies 3-dimensional deformation using speckle tracking echocardiography (3D-STE) to objectively define global and regional myocardial shortening amplitude and directionality, which is not affected by through-plane motion. It integrates circumferential (C), longitudinal (L), and C-L shear strains into a single deformation, expressed as PS lines (Fig. 1). Aim of this study was to apply PSA to characterize right ventricular (RV) function after Tetralogy of Fallot (TOF) repair.

Hypothesis:
PS provides novel description of RV function following TOF repair and may help determine subsequent need for pulmonary valve replacement (PVR).

Methods:
We prospectively enrolled 40 TOF patients (11.0±4.9 years) evaluated 10.0±4.5 years after corrective surgery, including 7 candidates awaiting PVR, and 40 age-matched controls (12.9±3.7 years). 3D-STE images were analyzed offline using Tomtec and Matlab-based post-processing software.

Results:
TOF patients had significantly larger RV volumes and decreased RVEF (EDVi: 106±18 versus 63±12 mL/m
2
, RVEF: 48±5 vs 57±4%, respectively, both p< 0.001). All global strain values were significantly decreased in TOF patients (GPS: -22.7±2.5 versus -25.8±2.0%, GCS: -10.6±3.4 versus -15.8±2.5%, GLS: -9.1± 6.3 versus -15.2±2.3%, GLS (2D): -20.3±4.5 versus -24.7±3.9 %, respectively, all p<0.001). Figure 2 shows PS magnitude and angle for control and TOF patient. Compared with controls, TOF patients demonstrated regionally lower PS strain (red areas) with preserved contractile angles. Among global strain amplitudes, PS showed best sensitivity (86%) and specificity (74%) for predicting subsequent need for PVR (Table1) (ROC: 0.76, cut off value: -22.9%).

Conclusions:
PS provides novel characterization of 3D RV deformation after TOF repair and is associated with subsequent need for PVR. Further research is warranted to determine its incremental value for guiding timing of PVR.
Abstract 15463: Pre-procedural Inr, Bleeding, and Mortality in the Catheterization Lab: Does INR Still Matter in the Radial First Era?
Authors: Misra Shantum , Andrus Bruce W , Devries James T
Published: November 2020

Background:
Warfarin anticoagulation presents a common barrier to undergoing cardiac catheterization procedures. Using radial access and other bleeding mitigation strategies, it is not known if elevated INR truly portends an increased risk of adverse events. We sought to understand the relationship between in hospital mortality and bleeding with INR in patients undergoing coronary interventional catheterization procedures.

Methods:
The prospectively-collected Dartmouth Dynamic Registry was queried for all patients who underwent catheterization with coronary intervention from 2014 to 2018. Of the 5015 patients identified, 2120 patients had a recorded INR value within 24 hours of the procedure. Demographics, procedural variables, and in hospital outcomes were collected. Patients were divided into two groups: INR <1.8 and INR >1.8. Incidence of bleeding (access site hematoma >5cm, post procedure blood transfusion) as well as in-hospital mortality were queried for each group. Stata was used to determine statistical significance, using chi-square analysis for categorical variables and standard t-test for continuous variables.

Results:
Of the 2120 patients with INR values, 1968 patients were identified with INR <1.8 (median INR 1.1; range 0.7-1.7) and 152 patients with INR >1.8 (median INR 2.2; range 1.8-11.1). Patients with elevated INRs had higher acuity (urgent or emergent cases) and were older. Other baseline and procedural characteristics were similar. Outcomes between those with elevated INR and those with lower INR values were similar, including access site injury, hematoma, and need for transfusion (Table I). Overall mortality did not differ between the two groups.

Conclusion:
When compared to patients with INR <1.8, patients with INR >1.8 are more likely to undergo coronary intervention on an urgent or emergent basis. Despite this, there is no difference in bleeding, need for transfusion, or overall in-hospital mortality.
Abstract 15465: Upregulation of Mitochondrial Atpase Inhibitory Factor 1 Mediates Increased Glycolysis in Pathological Cardiac Hypertrophy
Authors: Zhou Bo , Caudal Arianne , Tang Xiaoting , Chavez Juan D , Keller Andrew , Villet Outi M , Kolwicz Stephen C , Wang Wang , Bruce James , Tian Rong
Published: November 2020

Background:
During the development of heart failure cardiac fuel metabolism switches from predominantly fatty acid oxidation (FAO) to increased reliance on glucose, especially glycolysis. Mechanisms responsible for the switch are poorly understood but appear to be coupled with impaired mitochondrial function. We recently demonstrated that increased glucose metabolism is required for cardiomyocytes growth during pathological remodeling.

Hypothesis:
Upregulation of mitochondrial ATPase inhibitory factor 1 (ATPIF1) in hypertrophied hearts suppresses ATP synthesis and shifts cardiac metabolism from fatty acid oxidation towards glucose metabolism.

Methods and Results:
We report that ATPIF1 expression is upregulated in cardiomyocytes and mouse hearts undergoing pathological hypertrophy. Using genetic models of ATPIF1 gain- and loss-of-function in cardiomyocytes and in mouse hearts,we find that upregulation of ATPIF1 in cardiac hypertrophy inhibits ATP synthesis. Furthermore, quantitative analysis of chemical crosslinking by mass spectrometry revealed that increased expression of ATPIF1 promoted the formation of F
o
F
1
-ATP synthase nonproductive tetramer. Impairment of F
o
F
1
-ATP synthase function in respiring mitochondria increasedROS generation resulting in transcriptional activation of glycolysis. Cardiac-specific deletion of ATPIF1 in mice prevented the switch to glycolysis in pressure overload induced cardiac hypertrophy.

Conclusions:
We show that upregulation of ATPIF1 drives glucose metabolism at the expense of energy supply during the pathological growth of cardiomyocytes. Our study proposes a central role of ATP synthase in toggling anabolic and catabolic metabolism during pathological remodeling, illustrating a new concept for metabolic reprogramming of the heart.
Abstract 15466: Trajectory of Acute Coronary Syndrome Cases During the COVID-19 Pandemic
Authors: Desai Pooja S , Fanous Elias , Tan Weiyi , Parikh Rushi , Calfon Press Marcella , Rafique Asim
Published: November 2020

Background:
The COVID-19 pandemic was associated with a worrisome decrease in acute coronary syndrome (ACS) cases. We sought to investigate the trajectory of ACS following the relaxation of isolation orders and public service education.

Hypothesis:
We hypothesized that during the COVID-19 pandemic, ACS cases would decrease during the period of strict isolation and thereafter increase, illustrating a “rebound effect”, during the period of relaxed isolation.

Methods:
All adults with concern for ACS requiring cardiac catheterization at one academic center from 22 December 2019 to 13 June 2020 were included. Cases were designated as ST-elevation myocardial infarction (STEMI), STEMI activation, out-of-hospital cardiac arrest (OHCA), Non-STEMI/unstable angina (NSTEMI/UA), and/or total ACS. 18 December - 14 March, 15 March - 9 May, and 10 May - 13 June were designated as pre-isolation COVID-19 (piC), strict isolation COVID-19 (siC), and relaxed isolation COVID-19 (riC), respectively. Fisher’s exact test was used to compare average cases per week in piC vs. siC and siC vs. riC. One-way ANOVA was used to compare cases across piC, siC, and riC together. Analysis was completed with STATA/MP 16.1.

Results:
315 cases concerning for ACS requiring cardiac catherization lab activation were included. When comparing piC with siC and siC with riC, there were no significant differences in STEMI, STEMI activation, OHCA, NSTEMI/UA, or total ACS. When compared across piC, siC, and riC simultaneously there were no significant differences in STEMI (p=0.426), STEMI activation (p=0.172), OHCA (p=0.167), NSTEMI/UA (p=0.362), and total ACS (p=0.219). Total ACS, STEMI activation, NSTEMI/UA, and OHCA exhibited a trend towards a rebound effect (Graph).

Conclusions:
There were no significant changes in the incidence of total ACS, OHCA, STEMI, STEMI activation, or NSTEMI/UA between pre-isolation, strict isolation, and relaxed isolation periods of the COVID-19 pandemic.
Abstract 15469: Malnutrition and Cognitive Dysfunction in the Elderly Patients With Acute Heart Failure
Authors: NAGAI Michiaki , Dote Keigo , Kato Masaya , Oda Noboru , Kunita Eiji , Kagawa Eisuke , YAMANE AYA , Kobatake Hiroshi , Ayano Osawa , Ishibashi Naoki , Takahashi Kazuki
Published: November 2020

Introduction:
Malnutrition, cognitive decline and heart failure (HF) frequently coexist in the elderly. A recent systematic review revealed that malnutrition was a possible contributing factor of cognitive impairment. Although several studies reported the association of malnutrition with poor HF prognosis, the underlying pathophysiology has been unclear.

Hypothesis:
We assessed the hypothesis that malnutritional status might be associated with cognitive dysfunction in the elderly with HF. In addition, we investigated whether left ventricular ejection fraction (LVEF) moderates that relationship or not.

Methods:
Nutritional status and cognitive function were evaluated using the geriatric nutritional risk index (GNRI), controlling nutritional status (CONUT) score and mini-mental state examination (MMSE) in 245 elderly inpatients in stable phase of HF (82.9±6.0 years old, male 49.4%). Echocardiography was performed at admission. HF with preserved EF (HFpEF) was defined according to LVEF more than 50% (n=129).

Results:
According to the quartile of MMSE score (< 19, ≥19 to 27≤, >27), significant associations of MMSE score were observed with GNRI (89.1 vs 95.4 vs 95.5, p=0.004) and CONUT score (3.50 vs 2.71 vs 2.61, p=0.039) among three groups. In the logistic regression analysis adjusted for the confounders including age, gender, LVEF, brain natriuretic peptide level, systolic blood pressure at admission, diuretics and antihypertensive medication use, GNRI (β=0.96, 95%CI:0.93 to 0.99, p=0.008) and CONUT score (β=1.18, 95%CI:1.01 to 1.37, p=0.03) each was significantly associated with cognitive dysfunction (defined as MMSE score <19). According to the HF phenotype, GNRI (β=0.93, 95%CI:0.88 to 0.98, p=0.01) and CONUT (β=1.55, 95%CI:1.19 to 2.02, p=0.001) each had a significant relationship with cognitive dysfunction only in the group without HFpEF.

Conclusions:
In conclusion
,
lower GNRI and higher CONUT score were shown to be significant indicators of cognitive dysfunction in the elderly HF patients. These results highlight the importance of stratifying by nutritional status for a clinical intervention of cognitive dysfunction in the elderly patients without HFpEF.
Abstract 15471: Structural Valve Degeneration of Transcatheter Aortic Valve Replacement in a Veterans Affairs Population
Authors: Yang Rachel , Ponna Vimala , Shunk Kendrick A , Zimmet Jeffrey , Ge Liang , Tseng Elaine E
Published: November 2020

Introduction:
Transcatheter aortic valve replacement (TAVR), previously reserved for intermediate to prohibitive surgical risk, has now expanded to patients with severe aortic stenosis of any surgical risk. However, bioprostheses are prone to structural valve degeneration (SVD), a progressive process that limits valve durability. As the population undergoing TAVR shifts toward a lower-risk and younger profile, long-term durability is a crucial determinant for patient outcomes. Our objective was to report the characteristics of and assess risk factors for SVD in a veteran TAVR population.

Methods:
Patients undergoing TAVR at our Veterans Affairs Medical Center were retrospectively evaluated for SVD and other endpoints using recently standardized consensus criteria. Multivariate Cox proportional hazards analysis was performed to evaluate risk factors for SVD.

Results:
From 2013 to 2020, 312 patients (median age 79.0) underwent TAVR. Survival from all-cause mortality was 90.8% at 1 year, 76.1% at 3 years, and 64.0% at 5 years (Figure 1). Cumulative freedom from SVD was 98.0% at 1 year, 95.7% at 3 years, and 91.8% at 5 years. The 13 patients who met criteria for SVD were classified as moderate hemodynamic, and 2 required intervention. Median time to SVD was 1.04 years. Independent predictors of SVD include age (HR=0.92, CI:0.86-0.99) and valve size (HR=0.16, CI:0.03-0.81).

Conclusions:
SVD was evident at a low but detectable rate in 5 year follow-up, and associated with risk factors of patient age and implanted valve size. Further understanding of TAVR biomechanics will be essential to inform patient-specific risk of SVD. Figure 1: Kaplan-Meier curves of survival and freedom from SVD
Abstract 15477: Association With Post Discharge Adherence to Guideline Directed Medical Therapy and Long Term Health Outcome
Authors: Chen Chih-Wei , Huang Chun-Yao , Chien Li-Nien , Lin Yi-cheng
Published: November 2020

Introduction:
Statin, beta-blocker and Angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers have been advocated by guideline as secondary prevention medications to improve long term outcome post myocardial infarction for years. However, in reality, adherence to these medications have always been challenging and different treatment regimen adherence might lead to divergent outcomes which remains unclear in current AMI standard care.

Hypothesis:
To investigate the association between different guideline-directed medication regimen adherence post myocardial infarction and long-term outcomes.

Methods:
This cohort study used data files from Taiwan National Health Insurance Research Database (NHIRD). A total of 77520 survivors of hospitalization with AMI between 2002 and 2015 were assessed. Base on adherence to individual medications, eight treatment groups were estimated in this study. We investigate the association of adherence to different treatment groups and all-cause mortality in 24 months.

Results:
51322 STEMI patients and 26198 NSTEMI patients were included in the study. All treatment groups had significant higher mortality compare with patients who adhered to all 3 medications in 24 months follow-up. Patients not adherence to any medications had the highest mortality in 24 months (adjusted HR: 1.78; 95% CI: 1.64 to 1.93).

Conclusions:
In this large population base real-world data study, we found that adherence to all 3 secondary prevention medications in post myocardial infarction survivor was associated lower rate of all cause mortality.
Abstract 15480: Twiddler’s Syndrome in a Subcutaneous Implantable Cardioverter-Defibrillator
Authors: Jin Chengyue , Jacobson Jason , Iwai Sei , Ferrick Aileen M
Published: November 2020

Introduction:
Twiddler’s syndrome refers to deliberate or unintentional twisting of pulse generator in device pocket resulting in lead migration, which can present as malfunction of pacemaker or implantable cardioverter-defibrillator (ICD). In the past 50 years, twiddler’s syndrome with transvenous ICD and pacemaker has been well-described and thoroughly studied. However, there are very little data on twiddler’s syndrome with subcutaneous ICD (S-ICD).

Case presentation:
The patient is a 50-year-old male with a past medical history of hypertrophic cardiomyopathy, cardiac MRI showing left ventricular hypertrophy with a wall thickness of 24 mm, non-sustained ventricular tachycardia and evidence of late gadolinium enhancement scar, who underwent implantation of S-ICD for primary prevention. First follow-up 2 weeks post-implant showed appropriate device function. Two weeks later, remote monitor documented atrial fibrillation and ICD shocks. Surface ECG showed reduced R wave and delivered shock impedance was 7 ohms. Patient reported no symptoms and was clapping hands to music when it occurred. Chest X-Ray revealed S-ICD lead dislodged and retracted with coiling around the generator in the left lateral chest wall (Figure 1). Subsequently patient underwent lead revision and device replacement. To reduce the risk of future dislodgement, during re-implantation, the tip of the ICD lead was secured with 0-Silk.

Conclusion:
Twiddler’s syndrome is a rare complication after ICD implantation, not only with transvenous-ICDs but also involving S-ICDs. Risk factors include advanced and younger ages, redundant skin, obesity, oversized pocket, and psychiatric disorder. It can be a potentially dangerous and even fatal due to undetected or unsuccessful therapy for ventricular tachyarrythmias. Therefore, it is of paramount importance to diagnose and intervene early to avoid morbidity and mortality in these patients.
Abstract 15483: A Clinic-based Intervention Achieves Target Doses of Guideline-directed Medical Therapy in Heart Failure
Authors: Rogerson Ann , Allen marvin R , Beckstrand Renea L , Granger Bradi B
Published: November 2020

Introduction:
Target doses of guideline-directed medical therapy (GDMT) reduce morbidity and mortality, and yet, are challenging to achieve in patients with heart failure and reduced ejection fraction (HFrEF). Long-term, relationship-based approaches are not well described.

Methods:
We implemented a person-centered approach in a nurse-managed multidisciplinary heart failure clinic. We used repeated measures analysis to prospectively evaluate patient satisfaction, appointment attendance, dose optimization of GDMT for renin-angiotensin inhibitors, beta-blockers (BB), mineralocorticoid antagonists (MRA), and anticoagulation, and ICD placement and cardiac rehab participation at 12 months. GDMT was scored 0-6, with one point for each guideline-indicated therapy. Composite scores were compared using ANOVA at baseline, 6-months, and 12-months.

Results:
Participants (n=102) were age 68 (± 14.95) years on average, predominantly white (95.1%), male (62.75%), and high school graduates (88.24%). At 12-months, the proportion of patients on ≥50% of target doses improved: renin-antiotensin inhibitors from 27% to 41%, beta-blockers from 46% to 64%, and MRA from 35% to 65%. Cardiac rehab attendance improved from 25% to 84%. Patient satisfaction with care improved; four (3.9%) patients did not attend scheduled follow-up in the 12-month period. Though overall composite scores of GDMT improved (F=51.74,
p
<0.001), only 12% of patients achieved target doses for all 3 medication classes concomitantly. No participants were readmitted within 30 days of HF-hospitalization; all-cause 30-day readmission was 10.5%.

Conclusion:
A persistent patient-provider relationship and person-centered approach to HF management may improve GDMT.
Abstract 15484: Combined Coronary and Carotid Artery Involvement in a Caucasian Patient With Moyamoya Disease
Authors: Qavi Ahmed H
Published: November 2020

Introduction:
Moyamoya disease (MMD) is a rare, progressive steno-occlusive disease of the intracranial carotid arteries. This is primarily a cerebrovascular disease and is mostly seen in young Japanese patients. We report a case of severe stenosis in the distal left circumflex artery (dLCx) in a non-Japanese patient with previously diagnosed MMD.

Case presentation:
A 33-year-old Caucasian female with history of MMD and 2 CVAs presented with chest pain for 2 days. Her only medication at home was aspirin. There was no history of hypertension, diabetes mellitus, or tobacco use. There was no family history of early CAD. Physical examination was positive for tachycardia but negative for carotid or femoral bruits. Neurologic examination revealed decreased touch sensation and diminished deep tendon reflexes on the left side. ECG demonstrated tachycardia with T wave inversions in leads III and ST depression in lead II. Acute CVA was ruled out with an MRI. Cardiac troponins were minimally elevated with peak of 0.12 ng/dl. An initial diagnosis of NSTEMI was made; patient was loaded with aspirin, clopidogrel and started on a heparin drip. Cardiac catheterization on the following day revealed single vessel CAD in the dLCx, with 80% stenosis and TIMI flow 2. A drug eluting stent was successfully placed in the dLCx. Angiogram post-stent placement showed optimal angiographic result with TIMI 3 flow. The patient was discharged home on dual antiplatelet therapy, statin, beta-blocker and ACE inhibitor.

Discussion:
MMD is thought to affect the coronary arteries from fibrous intimal thickening and histopathology of these coronary lesions show a homogenous, soft intimal proliferation with minimum lipid deposition and without substantial inflammatory cell infiltration. Although the combined involvement of carotid and coronary artery stenosis is rare, coronary involvement should be considered as one of the causes of ischemic heart disease in young patients with MMD. To the best of our knowledge, this is the first reported case of combined involvement of carotid and coronary artery stenosis in a Caucasian patient with previously diagnosed MMD. It is imperative to educate patients with MMD about possible CAD so that they seek immediate medical attention if cardiac symptoms occur.
Abstract 15487: Combined Effects of Lipoprotein(a) and Hypertension in Predicting Cardiovascular Outcomes in Patients With Coronary Artery Disease
Authors: Liu Huihui , Cao Yexuan , Jin Jinglu , Zhang Hui-Wen , Hua Qi , Li Yan-Fang , Guo Yuan-Lin , Zhu Cheng-Gang , Wu Na-Qiong , Hua Qi , Gao Ying , Xu Rui-Xia , Sun Jing , Li Jian-Jun
Published: November 2020

Introduction:
Although emerging data have suggested that circulating lipoprotein(a) [Lp(a)] could predict cardiovascular events (CVEs) in patients with cardiovascular disease, no study is currently available regarding the prognostic significance of Lp(a) in patients with hypertension.

Hypothesis:
We assessed the hypothesis that there is a prognostic linkage between hypertension and Lp(a) concentrations in patients with coronary artery disease (CAD).

Methods:
A total of 8668 patients with stable CAD were consecutively enrolled. Baseline Lp(a) concentrations of them were measured. All subjects were categorized according to Lp(a) levels of <10 (low), 10-30 (medium) and 30 mg/dL (high) and were further stratified by hypertension status. They were regularly followed-up for the occurrence of cardiovascular death, non-fatal myocardial infarction and stroke.

Results:
Over an average of 54.81±18.60 months follow-up, 584 (6.7%) CVEs occurred. Kaplan-Meier and multivariate Cox regression analyses showed that elevated Lp(a) levels had a significant association with CVEs in hypertensive patients, regardless of the control status of blood pressure, but not in normotensive subjects. Moreover, when subgrouping according to both Lp(a) categories and hypertension status, the risk for CVEs was only significantly elevated in high Lp(a) plus hypertension group compared with the reference group with low Lp(a) levels and normotension (hazard ratio: 1.85, 95% confidence interval: 1.19-2.85).

Conclusions:
In conclusion, elevated Lp(a) was associated with higher risk for CVEs in CAD patients with hypertension and the coexistence of high Lp(a) concentrations and hypertension greatly worsened the clinical prognosis. Our findings may present a prognostic linkage between hypertension and Lp(a) concentrations in patients with CAD.
Abstract 15494: Physiological Investigation of the C57bl6 Mouse Aorta Reveals a Critical Role for Voltage Gated Calcium Channel Activity in Spontaneous Arterial Ageing
Authors: De Moudt Sofie , Hendrickx Jhana O , De Munck Dorien G , Leloup Arthur J , Martinet Wim , De Meyer Guido , Fransen Paul
Published: November 2020

Introduction:
Arterial stiffness (AS) has gained much recognition as a hallmark and independent predictor of cardiovascular (CV) events. Although generally assumed to be an adaptive response to increased blood pressure (BP), AS precedes hypertension in at least two experimental mouse models, thus revealing an incomplete understanding of AS pathophysiology.

Methods:
The current study presents the longitudinal CV characterization of spontaneously ageing C57Bl6 mice (2, 4, 6, 9, 12 and 24-month old) (male, n>8).
In vivo
analysis of peripheral BP (Coda), aortic pulse wave velocity (aPWV, Vevo2100), and echocardiography (Vevo2100) was combined with
ex vivo
aortic studies of isometric reactivity (organ baths) and AS measurements in the Rodent Oscillatory Tension set-up for Arterial Compliance (ROTSAC). (Data are presented as mean ± SEM.)

Results:
In vivo
and
ex vivo
characterisation confirms that aortic stiffness precedes peripheral BP alterations in spontaneously ageing C57Bl6 mice, with significantly and gradually increasing aPWV (Fig.A) and isobaric Peterson modulus (Ep) (Fig.B) from 6-month of age onward. Thereafter, cardiac hypertrophy was observed at 9-months of age (Fig.C), and peripheral BP measurement reveals elevated pulse pressure at 24-months (30% increase vs. all other ages) (Fig.D).
Ex vivo
investigation of the thoracic aorta shows increased contractions to phenylephrine (PE) in old (6-24 month) vs. young (2-4 month) mice (Fig.E,F) with an increased contribution of voltage-gated calcium channel (VGCC) (Fig.G,H) with age. Remarkably, no differences were observed on endothelial function, meaning that all changes occur on the level of the vascular smooth muscle cell (VSMC).

Conclusions:
Physiological ageing of VSMC results in high PE contractions, increased VGCC activity, and the development of significant arterial stiffening by 6-months of age. AS thereby precedes the development of peripheral BP alterations by 18 months.
Abstract 15499: The Increase of Proplatelets and Tpo in Circulation May be a New Pathological Mechanism of Thrombosis
Authors: Yang Mo , Li Liang , zhang hua , zeng kuan , Yang Yanqi
Published: November 2020

Introduction:
Platelets are produced from megakaryocytes, which mainly regulated by thrombopoietin (TPO) and 5-HT. We hypothesized that the secretion of inflammatory cytokines increased in patients with thrombosis under stress or inflammation, leading to increased TPO levels, which in turn increased production capacity of platelet, and increased the number of platelet intermediates proplatelets into the circulation. Therefore, the increase in the number of proplatelets in the circulation, and the increase in plasma TPO levels may be a new pathological mechanism of thrombosis.

Methods:
TPO was detected by ELISA. Proplatelets from patients were stained with CD41-FITC and further confirmed by a fluorescence microscope and flow cytometry. The
in vitro
proplatelets were tested by CD41-FITC staining under a fluorescence microscope and flow cytometry detection.

Results:
Our clinical data demonstrated that patients' plasma TPO levels were significantly higher with acute inflammation state compared with healthy subjects (181.1 ± 35.38 vs 96.1 ± 9.7 pg/ml, p<0.001, n=65). The plasma TPO levels of cerebral infarction patients (186.2±12.5 pg/ml, n=20) were significantly higher than that of the control group (122.3±10.2 pg/ml, n=20). The number of platelets in patients with cerebral infarction (222.11±8.55 х10
9
/L, n=20) was slightly higher than that in the control group (206.55±8.83 х10
9
/L, n=20). More large platelets or proplatelets were found in the circulating blood of patients with cerebral infarction, which was significantly different from the control group (n=8, p<0.05).
In vitro
study confirmed that in 200 megakaryocytes (MKs), more proplatelets were produced in the TPO group (100 ng/ml, 18±2.5%) and in the 5-HT group (100 nM, 15±3.2%), while the control group was only (7±3.2) % (n=5). The effects of TPO/ 5-HT were interfered with by its receptor blockers, confirming that their effects were mediated by its receptors. Both TPO and 5-HT affect the cytoskeleton by activating p-ERK1/2, reorganizing F-actin to generate proplatelets, and its role was blocked by PD98059.

Conclusions:
The studies showed that the increase of proplatelets in circulation and TPO levels in plasma may be a new pathological mechanism of cerebral infarction or thrombosis.
Abstract 15801: Early and Late Risk of Mortality or Development of Severe Pulmonary Hypertension Following Closure of Ventricular Septal Defects in Children With Severe Pulmonary Hypertension and Elevated Pulmonary Vascular Resistance Using Traditional or Uni-directional Flap Valve Patch Closure
Authors: Novick William M , Golovenko Oleksandr , Lazorhyshynets Vasyl , Dedovich Vitaly , Perepeka Iryna , Rudenko Maya , Prokopovych Lilia , DiSessa Thomas G
Published: November 2020

Introduction:
Children with large ventricular septal defects, severe pulmonary hypertension (PHT), and elevated pulmonary vascular resistance (PVR) are frequently denied operation in low and middle-income countries secondary to concerns of high mortality and development of severe pulmonary hypertension following operation, early and late.

Hypothesis:
We hypothesized that closure with a uni-directional flap valve patch (DP) would provide lower mortality and better survival without severe PHT.

Methods:
From 5/96 - 12/2016 all patients undergoing VSD closure with severe PHT and elevated PVR by either traditional (TP) or DP closure were followed annually. Baseline and O
2
provocation catheterization were performed before operation. Echocardiograms were performed at discharge and follow-up. The decision on TP or DP closure was based upon age and surgeon preference. Beginning in 2005 all patients regardless of technique received sildenafil 3 mgs/kg/day for 3 months before operation.

Results:
The number of patients receiving operation was 129, of which 40 received the DP. Males were 66/129, age and weight differed significantly for DP group compared to the TP group (7.5 vs 2.6 years, p<0.001 and 20 vs 11.5 kgs, p<0.001).Catheterization baseline data, PVR 9.0 vs 7.4 for DP and TP respectively (p<0.001), negative vasoactive test 32.5% vs 13.5% for DP and TP respectively (p=0.016). Mortality was 1/40 for DP and 9/89 for TP. Pulmonary to Systemic systolic pressure ratio was lower at discharge vs baseline cath (0.38 vs 0.99, p<0.001). Predictors of late severe pulmonary hypertension were PVR/SVR >0.5, p<0.024; and a negative vasoactive test of <10% decrease, p<0.001. PHT at last follow-up, none or mild 86/115 (74.8%), moderate 16/115 (13.9%) or severe 13/115 (11.3%).

Conclusions:
DP patients had less risk of death and both groups had few patients with severe PHT at late follow-up..
Abstract 15805: Longitudinal Changes in Univentricular Patients Pre-Bidirectional Cavopulmonary Connection and Pre-Fontan
Authors: Aly Safwat , Lam Christopher , Yoo Shi-Joon , Seed Mike , Chaturvedi Rajiv
Published: November 2020

Background:
Little is known about serial changes in the physiology of single ventricle (SV) patients during staged palliation and if HLHS patients differ from the rest.

Methods:
We analyzed SV patients who had a combined cath with CMR at
both
the preBCPC and preFontan studies from 2016-2019. Flow contrast mapping used to calculate pulmonary arterial (Qpa) and venous (Qpv) flow. Systemic blood flow (Qs) calculated using [superior vena cava (SVC) flow + descending aortic flow at the level diaphragm]. Cerebral vascular resistance (CVRi) calculated using [ascending aortic pressure (AoP)-right atrial pressure (RAP)/SVC flow]. Systemic vascular resistance (SVR) calculated using [(AoP-RaP)/Qs]. Pulmonary vascular resistance (PVR) was calculated using [(mean PAP - LAP)/Qpv].

Results:
30 patients were found, 10 with HLHS. The BCPC unloaded the heart, EDVi fell from preBCPC to preFontan. From preBCPC to preFontan(Table1): PA flow fell, but was compensated by increased APC flow to keep QpQs~1, PApressure and PVRi fell. Compared to others, the HLHS patients had larger hearts (EDVi) and lower PA but higher APC flow at
both
preBCPC(Table2)and preFontan(Table3). By preFontan, HLHS patients had worse function: higher ESVi, lower EF.

Conclusion:
QpQs ~1 is maintained by increase in APC flow. HLHS hearts are larger and deteriorate progressively.
Abstract 15811: Prevalent Pharmacotherapy in United States Children and Adolescents After Fontan Completion
Authors: Obyrne Michael L , Faerber Jen , Katcoff Hannah , Huang Jing , Edelson Jonathan , Finkelstein David , Avitabile Catherine , Glatz Andrew C , Goldberg David J
Published: November 2020

Background:
Patients who have undergone Fontan palliation are at life-long risk of significant morbidities including thrombosis, heart failure, and arrhythmia. At present there is limited evidence to guide pharmacotherapy and no recent studies have evaluated US pharmaceutical practice in this population.

Methods:
A retrospective observational study evaluating the prevalent use of prescription medications in children and adolescents with hypoplastic left heart syndrome or tricuspid atresia after Fontan completion (identified using ICD9/10 codes) was performed using data from the Marketscan® Commercial and Medicaid databases. Cardiac pharmaceuticals were divided by class and function. Anticoagualants, other than aspirin, which is not uniformly a prescription medication, were also studied. Associations between increasing age and the likelihood of a filled prescription for each class of drug were evaluated.

Results:
A cohort of 4056 subjects [median age 12 years (IQR: 8-16), 61% male, 60% commercial insurance] was identified. The most common medication classes were angiotensin converting enzyme inhibitors/angiotensin receptor blockers (ACEI/ARB), diuretics, cardiac glycosides, and pulmonary vasodilators (Table), although 50% received no prescription medications. Older age was associated with increased likelihood of receiving anticoagulants (p=0.008), antiarrhythmic agents, digoxin, ACEI/ARB, and beta blockers (each
p
<0.0001
),
but also lower likelihood of receiving pulmonary vasodilators, diuretics (both
p
<0.0001), and potassium sparing diuretics (
p
=0.02).

Conclusion:
Pharmacotherapy typically used to treat adult heart failure and pulmonary hypertension are the most commonly prescribed medications following Fontan palliation. Determining the optimal regimen for individual patients and the population at large is an important knowledge gap for future research.
Abstract 15818: Three-dimensional Electroanatomic Mapping of Human Ventricular Tachycardia
Authors: Pong Terrence , Cyr Kevin J , Aparicio Valenzuela Joy , Babakhanian Meghedi , Wang Paul J , LEE Anson M
Published: November 2020

Introduction:
The localization of sources responsible for erratic ventricular tachycardia signaling can be facilitated by high-resolution epicardial mapping. Here, we describe an approach for epicardial mapping using 3D printed electrode mapping arrays. We utilize these mapping arrays to perform global beat-to-beat epicardial mapping of
ex vivo
Langendorff perfused human hearts and demonstrate the ability to identify sources of ventricular tachycardia.

Hypothesis:
The identification of ventricular tachycardia sources can be facilitated by epicardial mapping with 3D printed flexible mapping arrays.

Methods:
Epicardial shells were printed using a stereolithography 3D printer using flexible photopolymer resin followed by coupling with custom-designed flexible electrode arrays. Global electroanatomic maps were obtained from Langendorff perfused human hearts during sinus rhythm and after extra stimulus pacing induced ventricular tachycardia.

Results:
We demonstrate the use of 3D-printed electrode mapping arrays to perform global electroanatomic mapping of the human ventricular epicardium. Flexible 3D printed electrode arrays facilitate high spatial-temporal capture of electrophysiological data in Langendorff perfused human hearts and are capable of identifying epicardial sites of ventricular tachycardia.

Conclusions:
We report on flexible electrode mapping arrays shaped to match the epicardial contours of the human left and right ventricle. We demonstrate the ability to perform high spatiotemporal resolution mapping of human epicardial signals and demonstrate beat-to-beat global capture of ventricular tachycardia.
Abstract 15820: Differential Myocardial Gene Expression of Glucose Transporters in Heart Transplant Recipients With and Without Diabetes Mellitus
Authors: Vanderheyden Marc , Delrue Leen , Verstreken Sofie , Dierckx Riet , Heggermont Ward , Bartunek Jozef
Published: November 2020

Introduction:
The Sodium Glucose cotransporter (SGLT) and glucose transporters(GLUTs) play a crucial role in cellular glucose transport. Although experimental data have shown differential regulation of GLUT4 and SGLT in diabetic cardiomyopathy, the impact of diabetes mellitus (DM) upon myocardial glucose transporters in humans remains undetermined.

Aim:
To better understand the impact of elevated glucose levels upon myocardial expression of glucose transporters, the endomyocardial gene expression of GLUT1, GLUT4 and SGLT1 was investigated in heart transplant(HTx) recipients, with and without DM, who received a heart from a DM- donor.

Methods:
At baseline(BL), immediately after HTx and 12 ± 2 months(FU) later, serial endomyocardial biopsies were procured in 26 Htx pts, free of clinical or histological rejection, at time of routine surveillance biopsy. Patients were categorized in DM+ (n = 13pts) and DM- (n = 13 pts), according to the presence of diabetes mellitus (DM) at FU.

Results:
Despite similar hemodynamics and HbA1c levels at BL, DM+ pts had higher HbA1c levels (46,00 ± 13,79 vs 38,33 ± 4,88; p < 0,05) at FU. No differences were noted in BL GLUT1, GLUT4 and SGLT gene expression between both groups. In DM- pts SGLT1(0,081 ± 0,080 vs 0,188 ± 0,108; p = 0,0036) , GLUT4(0,076 ± 0,068 vs 0,137 ± 0,065; p = 0,0011 )and GLUT1(0,020 ± 0,021 vs 0,022 ± 0,009; p = 0,043) increased significantly at FU whereas no change was observed in DM+ pts.

Conclusion:
Similar to experimental data, differential endomyocardial regulation in SGLT1 and GLUT4 was noted between DM+ and DM-pts with a blunted upregulation of glucose transporters at 1 year in DM+ HTx pts. These observations are in line with experimental data and suggest that myocardial glucose uptake is differentially regulated in DM+ HTx pts.
Abstract 15829: Temporal Characteristics of Intra-thoracic Impedance Before and After Heart Failure Hospitalizations in a Large Real-world Population of Patients With Cardiovascular Implanted Electronic Devices
Authors: Sarkar Shantanu , Koehler Jodi L , Warman Eddy
Published: November 2020

Introduction:
Intrathoracic impedance (IMP), measured in ICD/CRTD implantable devices, is a measure of intravascular blood volume and have been shown to correlate with intracardiac pressures. We investigated the temporal characteristics of IMP before and after HF events (HFE) in a large real-world cohort of patients (pts) with ICD/CRTD devices.

Methods:
We linked Optum© deidentified EHR dataset during the period from 2007-2017 to the Medtronic CareLink data warehouse. Pts with ICD/CRTD implants with IMP measurements were included. HFE was defined as an inpatient, ED, or observation unit stay with primary diagnosis of HF and IV diuretics administration. Temporal average of IMP measurement across all pts in the 60 days pre and post HFE were compared for HFE with and without readmission for HF within 60 days and in pts with no HFE.

Results:
A total of 17,886 pts with 1.8±1.2 years of follow-up met inclusion criteria. The average age was 66.6 ±12.3 years, with 72% being males, and 51% with ICD devices. A total of 1174 pts had 1425 HFE with no readmission and 282 pts had 295 HFE which were followed by readmission. A total of 17,839 pts had no HFE over 86,858 follow-up months. The average IMP during HFE, with and without readmission, and in pts with no HFE are shown in Fig. IMP decreases over a period of time prior to HFE and recovers due to treatment during HFE. The average IMP across all patients was lower on all 60 days pre and post HFE with readmission compared to HFE with no readmission (p<0.001) and both were lower compared to follow-up period with no HFE (p<0.001). The IMP recovers less often after HF events which are followed by readmission within 60 days compared to HF events with no readmission.

Conclusions:
In a large real-world population of pts with ICD/CRTD devices, on an average IMP reduces prior to and recovers during HFE. IMP was lower before and after HFE with readmission compared to HFE with no readmission. Readmission is more likely in pts with smaller impedance recovery after HF events.
Abstract 15833: Immune Checkpoint Inhibitor Myocarditis Subtypes are Determined by a Cd8-dependent Transcriptional Program
Authors: Finke Daniel , Heckmann Markus B , Salatzki Janek , Riffel Johannes , Herpel Esther , Meder Benjamin , Mueller Oliver J , Frey Norbert , Katus Hugo A , Leuschner Florian , Kaya Ziya , Lehmann Lorenz H
Published: November 2020

Introduction:
Immune checkpoint inhibitors (ICIs) are revolutionizing cancer treatment. Nevertheless, their increasing clinical use leads to higher rates of adverse immune related events (irAEs). One of those irAEs is the ICI-induced myocarditis (ICIM) - a rare phenomenon with an estimated mortality rate of up to 50%. We aimed to characterize the molecular changes of ICIM which are not yet understood completely.

Methods:
Patients suspected for ICIM were assessed in the cardio-oncology units of University Hospitals Heidelberg and Kiel. Via RNA sequencing of myocardial biopsies, we compared transcriptional changes of ICIM (n=9) with samples from dilatative cardiomyopathy (DCM, n=11) and virus-induced myocarditis (VIM, n=5).

Results:
Clinical analysis of 19 patients with ICIM showed an inconsistent presentation, e.g. an elevation of cardiac biomarkers (hsTnT, NT-proBNP, CK), a drop in leftventricular ejection fraction or late gadolinium enhancement in cMRI. We found 3784 (FDR <0.05) upregulated genes in ICIM. Among the genes that were related to antigen presentation and processing, we mainly found an upregulation of CD8. CD8-dependent clustering of ICI-patients, on the other hand, was associated with a number of immune cell-specific genes (compared to VIM: CXCL11 (log2 fc 3.24), CXCL9 (log2 fc 4.37), GBP6 (log2 fc 5.37), GBP5 (log2 fc 3.21). Analysis of high- and low-expressing CD8 positive biopsies identified two expression patterns, suggesting different pathological mechanisms for ICIM.

Conclusion:
Taken together, we were able to identify CD8 and CD8-associated genes as specifically regulated transcripts in ICIM. Moreover, based on the variable clinical phenotype, we propose that analysis of CD8 and CD8-dependent genes will be important to identify ICIM patients and to potentially sub-differentiate different phenotypes.
Abstract 15854: Early Cardiac Dysfunction in Obese Adolescents With Intellectual and Developmental Disabilities (idd)
Authors: HALIGHERI gEETHA , Tyler johnson , Melanie Kathol , Laura kuzava , Natalie Goth , France Rita , Donnelly Joseph , Ptomey Lauren , Forsha Daniel E
Published: November 2020

Early cardiac dysfunction in obese adolescents with intellectual and developmental disabilities (IDD)Background: Adolescents with IDD (IQ range 40-74) are more frequently obese than the general population and the IDD population has a higher risk of early cardiovascular (CV) mortality in adulthood. The relationship between obesity and echo strain has not been studied in those with IDD. We hypothesize that obese adolescents with IDD will have diminished LV strain vs non-obese controls. Methods: Non-obese (21/50; < 95
th
%ile BMI) and obese (29/50; > 95
th
%ile BMI) adolescents with IDD (Down syndrome (DS) or autism) were enrolled excluding those with congenital heart disease. Echo LV systolic measures included ejection fraction (bullet), myocardial performance index (MPI; tissue Doppler), 2D global longitudinal systolic strain (GLS), strain rate (GLSr) and global circumferential strain (GCS). LV diastolic measures were E/e’ and LV early diastolic strain rate (LV ED Sr). The RV measures included RV GLS and TAPSE. Statistical analyses included unpaired t-tests and simple linear regression, p≤0.05 significant. Results: In 50 subjects (age 16.9, range 13.3-21.8 yrs; 27/50 males), LV GLS and GCS were mildly diminished with normal LV volume and ejection fraction (Table). The obese group had diminished LV strain compared to the non-obese group (P < 0.001). Increased BMI %ile predicted diminished LV GLS (P < 0.001) and GCS (P < 0.001) as well as LV ED Sr (P=0.001) on regression analysis. RV GLS was also mildly diminished in the total cohort but not significantly diminished in the obese group (p=0.06). Diastolic function (E/e’) was abnormally elevated in the DS subgroup (only difference found between DS and autism subgroups). Conclusions: Obese adolescents with IDD had abnormal LV strain measures not detected by traditional echo emphasizing the need for successful weight loss strategies focused on this special population.
Abstract 15856: Peripheral Arterial Tonometry Has Low Sensibility for Cardiac Allograft Vasculopathy Detection
Authors: VEIGA BRUNO M , Lima Marina , Fontes Rafael , Brito Evandro C , Brandão Daniella , Dornelas de Andrade Armele , Carneiro Rodrigo , Figueira Fernando , Monteiro Verônica , Mello Maria
Published: November 2020

Introduction:
Cardiac allograft vasculopathy (CAV) is the main cause of chronic graft failure in cardiac transplant patients and plays a significant role in overall morbimortality of the post-transplantation population. In spite of the many available exams currently able to detect CAV subclinical development, they generally display important clinical limitations and lack early diagnosis sensibility. Therefore, the investigation of alternative technologies is essential for the better recognition and prevention of such condition.

Methods:
Exploratory study on the use of peripheral arterial tonometry as assessment of endothelial health of post-transplant patients. Patients were enrolled from Brazil’s 3rd largest heart transplant center, Instituto de Medicina Integral Professor Fernando Figueira, and subsequently evaluated with EndoPAT2000 between August 2019 and February 2020, when COVID-19 pandemic prematurely concluded the study. Eligible patients had at least 2 years of transplant afterlife and were regularly hospital monitored. The patients’ cardiac catheterism records were collected for more accurate comparison with endothelial results. Medications, preexisting conditions, and transplant information were acquired from medical records. The main outcomes consisted of peripheral arterial tonometry detection capability of endothelial abnormality degree and CAV.

Results:
Sample size of 22 patients (mean age 50.9, 90.9% men) submitted for EndoPAT2000 exam. Of these, 14 had prior catheterism records (3 had confirmed CAV, 2 coronary fistulas, 9 no abnormalities) and 9 didn′t. When compared with the non catheterism group (2.25 ± 0.41, 0.80 ± 0.19, 8.13 ± 12.21, 16.49 ± 13.87) patients who underwent the procedure (1.89 ± 0.56, 0.60 ± 0.28, 0.72 ± 10.78, 8.54 ± 12.69) had reasonably lower RHI, LnRHI, AI, and AI@75 respectively. CAV confirmed patients (1.99 ± 0.69, 0.65 ± 0.34, -2.07 ± 3.72, 4.40 ± 6.74) had no significant RHI differences, yet displayed slightly lower AI values.

Conclusion:
The findings of this study suggest there was no significant difference of endothelial health per peripheral arterial tonometry examination between the average catheterism population and CAV patients. Larger studies are needed to confirm such findings.