bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 10466: Post-myocardial Infarction Treatment With Edetate Disodium was Safe in the Trial to Assess Chelation Therapy
Authors: Drisko Jeanne , Alexander Karen P , Roberts Rhonda S , Chappell L. Terry , Lee Kerry L , Boineau Robin , Mark Daniel B , Nahin Richard L , Goertz Christine , Rosenberg Yves , Lamas Gervasio A
Published: July 2021

Introduction:
Treatment with edetate disodium has been in use for nearly 60 years for cardiovascular disease despite safety concerns, including deaths from hypocalcemia. No careful prospective evaluation of safety had been reported prior to the NIH-sponsored Trial to Assess Chelation Therapy (TACT).

Methods:
In TACT, 1,708 post-MI patients age ≥ 50 and creatinine ≤ 2.0 mg/dL were randomized doule blind to edetate-based chelation (n=839) or placebo (n=869). TACT implemented extensive site education prior to site activation. During the infusion period, there was close monitoring of vitals and labs, particularly creatinine and calcium, special lab-based (creatinine, calcium, and platelets) algorithms to delay infusions or reduce infusion rate when abnormal criteria were met, and early intervention to respond to safety concerns. Electronic and in-person monitoring took place to ensure adherence to TACT infusion protocols.

Results:
There were 100 (12%) serious adverse events (SAEs) in the edetate group and 127 (15%) in the placebo group (p=0.1009). Two deaths were possibly or definitely attributed, by the blinded safety monitor, to study therapy, 1 in the chelation group and 1 in the placebo group. Heart failure was reported in 57 edetate patients (7%) and 71 placebo patients (8%) (p=.28). Physical exams were identical over the course of the study, except for more tachycardia (heart rate >100) in the placebo arm (0.1% vs 1.3% p=0.006). There was more infusion site discomfort (1.5% vs. 0.6%, p=0.049) with chelation and more abdominal cramping with placebo (1.7% v. 3.3%, p= 0.029) Reductions in calcium (<8.5mg/dL) occurred in 52 chelation patients (6.2%) and 30 placebo patients (3.5%) during the infusion phase (p=.008). Calcium at last blood draw was not different between groups (mean calcium 9.3 vs 9.3, p=0.15). There was no adverse effect on renal function from edetate disodium (mean creatinine 1.04 (edetate) vs 1.07 (placebo), p=0.03)

Conclusions:
The experience with 55,222 infusions of edetate disodium or placebo in TACT shows that this therapy is extremely safe when used according to the TACT safe infusion protocol. This finding will be pivotal in informing the design of the TACT2 confirmatory study.
Abstract 10821: The Presence of Non-obstructive Coronary Artery Disease on Coronary Computed Tomography Angiography Re-classifies Guideline-based Statin Eligibility
Authors: Emami Hamed , Takx Richard , Mayrhofer Thomas , Janjua Sumbal , Park Jakob , Pursnani Amit , Lu Michael T , Ferencik Maros , Hoffmann Udo
Published: July 2021

Background:
AHA/ACC guidelines advise using 7.5% threshold of 10-year risk for atherosclerotic cardiovascular disease (ASCVD) events to determine eligibility for statin therapy. Coronary Computed Tomography Angiography (CTA) provides prognostic information for ASCVD events as well. We tested the hypothesis whether presence of non-obstructive CAD (<50% stenosis) as detected by CTA could be used to improve risk assessment per AHA/ACC guidelines in stable patients.

Methods:
We performed a systematic literature review to identify studies that assessed the prognostic value of coronary CTA findings for ASCVD events. The characteristics of study subjects at baseline, follow-up information, and outcomes were collected. We selected studies that provided hazard ratio (HR) for ASCVD events in patients with non-obstructive CAD and performed a meta-analysis. We incorporated the pooled HR into the standard 10-year ASCVD pooled cohort equation and derived equivalents for the 7.5% 10 year event risk for those with and without non-obstructive CAD and performed a sensitivity analysis using the lower and upper bounds of the confidence intervals of the pooled HR from the meta-analysis.

Results:
We identified 20 studies (22,036 subjects, 53% male, median follow-up 31 months) that assessed the prognostic value of CAD as detected by CTA. The studies that provided HR for ASCVD events were used for the meta-analysis. The pooled HR for incident ASCVD was 3.2 (95% CI 1.5-6.7). Equivalents for the 7.5% 10 year event risk for those with non-obstructive CAD were as low as 2.0% (African American women) and for those with no CAD as high as 33.8% (African American men). (Table 1)

Conclusions:
Non-obstructive CAD is an independent predictor of ASCVD events. Incorporating information on the presence of non-obstructive CAD into the AHA/ACC ASCVD risk calculator provides gender and ethnicity specific equivalents for the 7.5% threshold, which may improve efficiency and accuracy of statin therapy.
Abstract 10851: Effect of Glycemic State on Postprandial Hyperlipidemia and Hyperinsulinemia in Patients With Coronary Artery Disease
Authors: Nakamura Akihiro , Monma Yuto , Kajitani Shoko , Terui Yosuke , Noda Kazuki , Nakajima Sota , Endo Hideaki , Takahashi Tohru , Nozaki Eiji
Published: July 2021

Background:
Both postprandial hyperlipidemia and hyperinsulinemia have been thought to play an important role in the development of atherosclerosis, and to be a potent risk factor for cardiovascular event.

Methods:
To examine effects of glycemic state on postprandial hyperlipidemia and hyperinsulinemia in patients with coronary artery disease (CAD), a total of 146 consecutive male patients with angiographically confirmed CAD were loaded with a high-fat and high-glucose test meal. CAD patients were divided into three groups as “non-diabetic”, “prediabetic”, and “diabetic” CAD groups. 28 male normoglycemic patients without CAD matched on age were served as control subjects.

Results:
The serum triglyceride (TG) and remnant-like particle cholesterol (RLP-C) levels at the 6th hour in diabetic CAD group showed significantly higher than non-diabetic CAD group, and the area under the curves (AUCs) of these levels in diabetic CAD group were significantly greater than non-diabetic CAD group (TG, P = 0.0287; RLP-C, P = 0.0386). There were no significant differences in the AUCs of TG or RLP-C between prediabetic and non-diabetic CAD group. The AUCs of plasma insulin levels or insulin resistance index (IRI): (AUCs of insulin) x (AUCs of glucose) as the insulin resistance marker were greater in diabetic CAD group than non-diabetic CAD group (insulin, P = 0.0311; IRI, P = 0.0235). The AUCs of serum TG or RLP-C levels showed a correlation with the AUCs of plasma insulin (AUC-TG, r = 0.4381, P <0.0001; AUC-RLC-P, r = 0.3953, P <0.0001), and they correlated well with the insulin resistance index (AUC-TG, r = 0.7194, P <0.0001; AUC-RLC-P, r = 0.6621, P <0.0001). Conclusions: We found that the insulin resistance showed a close relationship with postprandial hyperlipidemia in CAD patients. Diabetic, but not prediabetic state, may be a risk for postprandial impaired lipid metabolism.
Abstract 10876: Speckle-tracking vs. Pressure-Volume Loop Measures of Left Ventricular Systolic Function in Children: An Inter-vendor Comparison
Authors: Chowdhury Shahryar M , Butts Ryan J , Taylor Carolyn L , Chessa Karen S , Hlavacek Anthony M , Shirali Girish S , Nutting Arni , Baker George H
Published: July 2021

Introduction:
The variability in speckle-tracking echocardiography (STE) algorithms between vendors is well recognized. While some are attempting to standardize algorithms across vendors, it is currently unknown which algorithm best compares to gold-standard measures of systolic function. The objective of this study was to compare STE measures of deformation from two vendors vs. gold-standard measures of LV contractility and global ventricular efficiency in children.

Methods:
Children with normal loading conditions undergoing routine left heart catheterization were prospectively enrolled. Pressure-volume loops were obtained via conductance catheterization. The gold-standard measure of contractility, end-systolic elastance (Ees), was obtained via balloon occlusion of the vena cavae. Ventriculo-arterial coupling was assessed using the arterial elastance to Ees ratio (Ea/ Ees). STE was performed immediately after PVL analysis under the same anesthetic conditions. Offline STE analysis was perfomed using both QLAB v9.0 (Phillips, Andover, MA) and Cardiac Performance Analysis v3.0 (Tomtec, Hamden, CT) by a single blinded observer. The relationships between PVL and STE measures of systolic function were determined using Spearman’s correlation.

Results:
Of 24 patients, 18 patients were s/p heart transplant, 6 patients had a small patent ductus arteriosus or small coronary fistula. Mean age was 9.1 ± 5.6 years. The average invasive Ees was 3.04 ± 1.65 mmHg/mL. The average Ea/Ees was 0.88 ± 0.35. Correlations between invasive Ees and Ea/Ees to STE measures of deformation are reported in the Table.

Conclusion:
STE measures of GLS and GLSR derived from Cardiac Performance Analysis have better correlation with gold-standard measures of cardiac performance when compared to QLAB. GCS derived from both vendors has no correlation to invasive measures. Attempts to standardize STE algorithms should take these results into consideration.
Abstract 10902: Association Between Funding Sources and the Scope and Outcomes of Cardiovascular Clinical Trials: A Systematic Review
Authors: Vaduganathan Muthiah , Samman-Tahhan Ayman , Papadimitriou Lampros , Georgiopoulou Vasiliki V , Greene Stephen J , Kalogeropoulos Andreas P , Peterson Eric , Fonarow Gregg C , Gheorghiade Mihai , Butler Javed
Published: July 2021

Introduction:
Limited data are available exploring trends and influence of funding sources on cardiovascular clinical trials scope and outcomes.

Methods:
We abstracted data from all phase II to IV cardiovascular clinical trials from 2001 to 2012 published in the 8 highest Web of Science impact factor journals using both a PubMed database and manual journal search.

Results:
Of the 1,224 trials evaluated, 581 (47.5%) were funded by industry, 273 (22.3%) by universities or other non-profit organizations, 159 (13%) by governments, 127 (10.4%) were jointly funded, and 84 (6.9%) did not report funding source. Proportion of industry and government funded trials trended down, while the proportion of non-profit and jointly-funded trials increased over time (P<0.001;
Figure
). Non-profit trials had the highest enrollment rates (P<0.001), while industry trials (44.1%) more commonly evaluated new therapies vs. placebo compared with other funding sources (P<0.001;
Table
). Positive outcomes were more likely to be reported by industry (65.6%) and non-profit (66.3%) trials compared to government (50.3%) or jointly-funded (45.7%) trials (P<0.001). After accounting for major trial characteristics, industry-funded (OR 2.37; 95% CI 1.61-3.49) and non-profit (OR 1.91; 95% CI 1.24-2.94) studies were more likely to report favorable outcomes compared with government-sponsored trials.

Conclusions:
Funding sources of cardiovascular clinical trials are associated with various aspects of trial conduct and outcomes. Further research is required to explore the systematic influence of funding mechanisms on contemporary cardiovascular clinical trials.
Abstract 10903: Extraction Outcomes in Patients With Congenital Heart Disease
Authors: Fender Erin A , Killu Ammar M , Hodge David O , Cannon Bryan C , Friedman Paul A , Mcleod Christopher J , Broberg Craig S , Henrikson Charles A , Cha Yong-Mei
Published: July 2021

Introduction:
Patients with congenital heart disease (CHD) frequently require implantable cardiac devices. Device infection or malfunction may necessitate lead extraction. Extraction may be challenging due to long lead dwell times, anatomic abnormalities, and prior cardiac surgery. Little is known about extraction outcomes in the CHD population.

Methods and Results:
This retrospective study included 41 CHD patients and 82 age and gender matched controls that underwent lead extractions at two centers between 2001-2014. Only patients with leads older than 12 months were included. There were 79 leads in CHD patients and 150 in controls. Patients with CHD had a mean age of 39±17 years at extraction and on average their leads had been implanted for 81±84 months, this was not significantly different from the control group. Eighty eight percent of CHD patients had 1 or more cardiac surgeries as compared to only 22% of controls (p<0.001). The number of abandoned leads was also significantly different with 16 abandoned leads in the CHD group and 3 in controls (p<0.001). There was no statistically significant difference in extraction techniques between the groups. Complete extraction was achieved in 94% of patients in both groups. There were no CHD group complications. Control group complications included 3 SVC lacerations requiring sternotomy (one was fatal), and 1 ventricular perforations with tamponade requiring sternotomy. None of these patients had a history of cardiac surgery. The average age of leads in patients with a complication was 15.3 years which was older than the mean lead age seen in the CHD and control populations which was 6.75 and 4.6 years respectively.

Conclusions:
Lead extraction can be safely performed in patients with CHD. Despite anatomic abnormalities and previous cardiac surgery, the outcome of lead extraction in patients with CHD is comparable to controls. Prior cardiac surgery may lower the risk for extraction complications.
Abstract 10946: Blockade of NKG2D / NKG2D Ligands Interaction Attenuated Cardiac Remodeling After Myocardial Infarction
Authors: Matsumoto Kotaro , Obana Masanori , Hashizume Rina , Yokoyama Yukari , Miyagawa Shigeru , Mohri Tomomi , Maeda Makiko , Nakayama Hiroyuki , Sawa Yoshiki , Fujio Yasushi
Published: July 2021

Background

The activating receptor Natural Killer Group 2 member D (NKG2D), expressed on immune cells such as NK, NKT and γδ T cells, contributes to eliminating infected or tumor cells by recognizing NKG2D ligands (NKG2DL). Accumulating evidence demonstrates that immune responses are involved in cardiovascular diseases; however, how cardiomyocyte death is induced by immune reactions in heart failure remains to be fully elucidated. Here, we examined the involvement of NKG2D/NKG2DL-mediated cell death in the progression of heart failure after myocardial infarction (MI).

Methods and Results

Murine MI was generated by ligating left anterior descending artery. Quantitative reverse transcription polymerase chain reaction (RT-PCR) demonstrated that NKG2DL, especially Rae-1ε, and NKG2D were up-regulated and reached the peak at day 3 (32 fold v.s. control) and day 7 (22 fold v.s. control), respectively, after MI. Moreover, immunohistochemical analysis revealed that Rae-1 was expressed in the infarct and border area of the post-infarcted hearts. To identify the NKG2D-expressing cells which infiltrated post-infarcted myocardium, flow cytometric analysis was performed using anti-CD49b antibody, NK cell marker, or anti-γδ TCR antibody, γδ T cell marker. Intriguingly, NKG2D-expressing immune cells were mainly γδ T cells, but not NK cells. Finally, to examine the pathophysiological role of the NKG2D/NKG2DL interaction in cardiac remodeling, MI mice were intraperitoneally treated with anti-Rae-1ε antibody or control IgG. Anti-Rae-1ε antibody administration suppressed cardiac fibrosis at day 14 after MI compared with control (control: 45.5%, anti-Rae-1ε antibody: 30.2%) assessed by Masson’s trichrome staining. Furthermore, TUNEL staining showed that apoptosis of cardiomyocytes was reduced by anti-Rae-1ε antibody treatment at day 3 after MI.

Conclusion

Blockade of NKG2D/NKG2DL interaction suppressed cardiac injury and death, preventing the progression of heart failure. NKG2D/NKG2DL could be a novel therapeutic target for heart failure.
Abstract 10961: QRS Duration and Left Bundle Branch Block Do Not Deter Assessment of Low Voltage in Cardiac Amyloidosis
Authors: Sperry Brett W , Vranian Michael N , Joshi Hariom , Hachamovitch Rory , Hanna Mazen
Published: July 2021

Introduction:
Left bundle branch block (LBBB) with QRS duration > 120 msec is typically associated with increased ECG voltage without a necessary increase in left ventricular wall thickness. Studies assessing voltage criteria in amyloidosis and other cardiomyopathies have excluded patients with LBBB. We sought to assess the effects of QRS duration and LBBB on voltage criteria in cardiac amyloidosis.

Methods:
We performed a retrospective analysis of patients with newly diagnosed cardiac amyloidosis at our institution from 2001-2014. Low voltage in the precordial leads was defined by the Sokolow criteria (S wave in V1 plus R wave in V5 or V6 ≤ 15mm). Limb lead voltage was calculated by the sum of the entire QRS complex voltage of leads I, II and III with low voltage being defined as each lead ≤ 5 mm. Patients with left bundle branch block were propensity matched to assess voltage criteria based upon age, sex, history of HTN, amyloid type (AL vs TTR), anteroseptal thickness and BSA to those with QRS < 120msec.

Results:
In 299 subjects (age 69.6 +/- 11.7 years, male 69%, HTN 53%, AL 53%, IVS 18.1 +/- 4.1 mm, BSA 1.95 +/- 0.26, EF 48 +/- 14%), mean QRS duration was 107 +/- 25 msec with 71 patients (24%) having a QRS duration greater than 120 msec (17 LBBB). The average limb voltage was 15.1 +/- 7.3 mm with low limb lead voltage seen in 62% of patients. Low precordial lead voltage was found in 73% of patients with a mean Sokolow voltage of 12.9 +/- 7.5 mm. After propensity matching the 17 patients with LBBB on a 1:3 basis with patients with a narrow complex QRS, there was no difference in any measure of voltage criteria.

Conclusion:
LBBB is not associated with higher voltage and does not hinder the ability to detect low voltage in patients with cardiac amyloidosis.
Abstract 10982: Persistence of “Gender Gap” in St-segment Elevation Myocardial Infarction Networks
Authors: Fernández-Rodríguez Diego , Regueiro Ander , Freixa Xavier , Trilla Marc , Masotti Mónica
Published: July 2021

Introduction:
Prognosis and management of women with ST-segment elevation myocardial infarction remains controversial.

Hypothesis:
The gender (female sex) influences the prognosis and the care of patients in a regional myocardial infarction network.

Methods:
Outcomes of patients activated by the Catalan network between January 2010 and December 2011, were analyzed according to gender. Time intervals, revascularization proportion, type of revascularization, in-hospital all-cause mortality and complications, 30-day all-cause mortality and one-year all-cause mortality were evaluated.

Results:
From a total of 5831 patients activated by the myocardial infarction network, 4380 patients had a diagnosis of ST-segment elevation myocardial infarction, and 961 (21.9%) of them were women. Women were older (69.8±13.4 vs. 60.6±12.8, p<0.001), had a higher prevalence of diabetes (27.1% vs. 18.1%, pI (24.9% vs. 17.3%, p<0.001), and no reperfusion (8.8% vs. 5.2%, p<0.001) as compared with men. In addition, women had greater time delays in medical care (first medical contact-to-balloon: 132-minutes vs. 122-minutes, p<0.001; symptoms onset-to-balloon: 236-minutes vs. 210-minutes, p<0.001). Women presented higher percentages of overall in-hospital complications (20.6% vs. 17.4%, p=0.031), in-hospital mortality (4.8% vs. 2.6%, p=0.001), 30-day mortality (9.1% vs. 4.5%, p<0.001) and one-year mortality (14.0% vs. 8.3%, p<0.001) compared with men. Nevertheless, after multivariate adjustment, no differences in 30-day and one-year mortality were observed (30-day adjusted hazard ratio [95% confidence interval]: 1.25 [0.94-1.65], p=0.123; one-year adjusted hazard ratio [95% confidence interval]: 0.88 [0.69-1.07], p=0.128). .

Conclusions:
Despite a higher risk profile and poorer medical management, women present similar 30-day and one-year outcome as their male counterparts in the context of myocardial infarction network.
Abstract 10983: Alcohol Intake and Heart Failure Incidence: Results From the Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Miller P. Elliott , Zhao Di , McClelland Robyn , Bertoni Alan , Lima Joao A , Guallar Eliseo , Post Wendy S
Published: July 2021

Background:
Alcohol intake has a well-described J-shaped effect on cardiovascular disease and all-cause mortality. Previous studies have shown a lower incidence of heart failure (HF) with moderate alcohol use. However, it is unknown whether alcohol intake is associated with a lower incidence of HF with reduced ejection fraction (HFrEF) or with preserved ejection fraction (HFpEF).

Methods:
We performed analyses of participants from the Multi-Ethnic Study of Atherosclerosis (MESA) to assess the association of alcohol and incident HF. Alcohol use was determine by self-report at baseline. Individuals were free of cardiovascular disease at baseline and were followed for a mean of 10.2 ± 2.8 years for incident events. Heart failure was classified as HFrEF (ejection fraction (EF) ≤50%) or HFpEF (EF > 50%) at the time of HF diagnosis. We performed time-fixed Cox proportional hazard regression models to assess associations between alcohol use and incident heart failure. Analyses were adjusted for age, sex, race, smoking (pack-years), and education, and then additionally for systolic and diastolic blood pressures, use of antihypertensive medications, family history of CHD, diabetes, HDL-cholesterol, C-reactive protein, fibrinogen, and interim myocardial infarction as a time-varying covariate.

Results:
We identified 6,763 individuals with alcohol use data, which included 1,390 (20.6%) never, 1,624 (24.0%) former, and 3,749 (55.4%) current drinkers at baseline. The average age was 62.1 years with 47.2% men. There were 258 HF events with 118 classified as HFrEF, 112 as HFpEF, and 28 participants excluded from analyses due to an unknown EF. Compared to never drinkers, individuals reporting > 2 drinks per day had a higher risk of developing HFpEF [HR 2.41 (95% CI 1.04, 5.60) in model 1 and HR: 2.65 (1.10-6.42) in the fully adjusted model]. There were no significant associations between alcohol use and incident overall HF (HFpEF and HFrEF combined) [HR 1.31 (0.73-2.35)] or HFrEF [HR 0.78 (0.32-1.92)].

Conclusion:
In the MESA cohort, individuals who drank greater than 2 alcoholic drinks per day had an increased odds of incident HFpEF but not HFrEF. Follow-up studies are needed to understand the etiology of these differences and to investigate for differences by race and sex.
Abstract 11015: Why Don’t Heart Failure Patients Respond to Worsening Symptoms?
Authors: Lin Chin-Yen , Dracup Kathleen , Pelter Michele M , Biddle Martha J , Moser Debra K
Published: July 2021

Background:
Long delays in seeking medical care are common in patients with worsening symptoms of heart failure (HF) and lead to longer lengths of hospital stay, increased healthcare costs, and increased morbidity and mortality. However, patient-reported reasons for delay have rarely been explored.

Objective:
To describe patient-reported reasons for delay in seeking medical care for worsening symptoms.

Methods:
As part of a clinical trial designed to reduce HF readmission and mortality for worsening symptoms, we administered the HF Symptom Response Questionnaire to all patients prior to intervention. The instrument measures reasons why patients delay seeking treatment. All patients had a recent hospitalization for HF, were community dwelling in a rural location, and had no cognitive impairments as measured with the Mini-Cog.

Results:
A total of 614 HF patients (59% male, NYHA class III/IV 35%, 19% without a high school education, mean age 66±13 years, median b-type natriuretic peptide level 186 pg/ml [25th percentile = 72, 75th percentile = 462] were studied. The most common reasons for not seeking early treatment were symptom uncertainty (62.4%), symptoms seem vague or came on too gradually (67.4%), symptoms slightly different from last episode (55.2%) and the symptoms didn’t seem to be serious enough (62.2%). Other reasons include embarrassment at seeking treatment (23.9%), not wanting to second guess the doctor (21.7%), financial concerns (19.9%), transportation issues (16.4%), and other (10.7%). Reasons given in the other category included afraid/don’t like doctors or hospitals, care of pets at home, family needs them, not wanting to bother others, denial/don’t want to know/fear of knowing, and weather.

Conclusions:
Despite experiencing worsening HF symptoms of such intensity that hospitalization is required, most patients do not perceive that symptoms are intense or certain enough to warrant action. In many, treatment seeking decisions are superseded by factors not related to symptom appraisal such as family obligations, fear or denial, and embarrassment. Education to improve response to worsening HF symptoms requires skills in symptom appraisal, and counseling to overcome personal barriers to seeking treatment.
Abstract 11029: Netrin-1 Alleviates Post-Resuscitation Myocardial Dysfunction in a Rat Model of Cardiac Arrest
Authors: Yin Lu , Zhao Shen , Moon JoongBum , Sun Peng , Wang Jiangang , Yu Haifang , Tang Ziren , Wu Xiaobo , Wu Xiaobo , Cahoon Jena , Tang Wanchun
Published: July 2021

Introduction:
Post-resuscitation myocardial dysfunction has been recognized as one of the major causes of fatal outcomes after initial successful cardiopulmonary resuscitation (CPR). Previous research demonstrated that Netrin-1 improved post ischemic injury cardiac function via preservation of mitochondrial integrity. In the present study, we investigated the role of netrin-1 after cardiac arrest.

Hypothesis:
We hypothesized that the netrin-1 alleviated post-resuscitation myocardial dysfunction in a rat model of cardiac arrest.

Methods:
A total of sixteen male Sprague-Dawley rats (450-550 g) were randomized to two groups as follows: (1) Control group (C group); (2) Netrin-1 group (N group). Ventricular fibrillation was induced and untreated for 8 mins followed by 8 mins of CPR. Netrin-1 or saline were given at the onset of precordial compression. Ejection fraction (EF) was measured by echocardiography at baseline, 1,2,3 and 4 hours after ROSC.

Results:
Eight rats were resuscitated in the netrin-1 group and 7 rats were resuscitated in the saline group. In both groups, EF decreased after resuscitation when compared to the baseline (#p < 0.05). In the netrin-1 group, EF decreased from ( 68.1±3.4)% at baseline to (51.1±5.0)% at 1 hour post-resuscitation. In the saline group, EF decreased from (67.7±2.1)% at baseline to (44.5±5.3)% at 1 hr post-resuscitation. EF was better in the netrin-1 group than in the saline group at 2, 3 and 4 hours post-resuscitation (*p < 0.05) ( Figure 1).

Conclusion:
Netrin-1 alleviates post-resuscitation myocardial dysfunction in a rat model of cardiac arrest.
Abstract 11041: Use of Digoxin is Associated With Reduced Interstage Mortality: Results From the Pediatric Heart Network Single Ventricle Reconstruction Trial
Authors: Oster Matthew , Kelleman Michael , McCracken Courtney , Ohye Richard P , Mahle William T
Published: July 2021

Introduction:
Despite medical and surgical advances over the past few decades, mortality for infants with single ventricle congenital heart disease remains as high as 8-12% during the interstage period, the time between discharge after the Norwood procedure and before the stage II palliation. The objective of our study was to determine the effect of digoxin use on interstage mortality in infants with single ventricle congenital heart disease.

Hypothesis:
We hypothesized that digoxin would be associated with lower interstage mortality.

Methods:
We conducted a retrospective cohort study using the Pediatric Heart Network Single Ventricle Reconstruction Trial public use dataset, which includes data on infants with single right ventricle congenital heart disease randomized to receive either a Blalock-Taussig shunt or right ventricle-to-pulmonary artery shunt during the Norwood procedure at 15 institutions in North America from 2005-2008. Parametric survival models were used to compare the risk of interstage mortality between those discharged to home on digoxin vs. those discharged to home not on digoxin, adjusting for center volume, ascending aorta diameter, shunt type, and socioeconomic status. Further comparisons were made to compare the number of other adverse events in the two groups.

Results:
Of the 330 infants eligible for this study, 102 (31%) were discharged home on digoxin. Interstage mortality for those not on digoxin was 12.3%, compared to 2.9% among those on digoxin (Figure), with a number needed to treat of 11 patients to prevent one death. The adjusted hazard ratio was 3.5 (95%CI 1.1-11.7, p=0.04). There were no differences in complications between the two groups during the interstage period.

Conclusions:
Digoxin use in infants with single ventricle congenital heart disease is associated with significantly reduced interstage mortality and should be considered for all such infants unless otherwise contraindicated.
Abstract 11093: Layer-specific Quantification of Myocardial Deformation by Strain Echocardiography May Reveal the Mechanism of Preserved Left Ventricular Ejection Fraction in Patients With Hypertrophic Cardiomyopathy
Authors: Sun Jing Ping , Ni Xianda , Xu Tingyan , Xu Min , Yang Xing Sheng , Lee Alex PW , Fang Fang , Yu Cheuk-Man
Published: July 2021

Purpose:
We aimed to evaluate compensatory mechanisms in hypertrophic cardiomyopathy (HCM) patients (pts) with preserved left-ventricular (LV) ejection fraction (EF).

Methods:
Speckle-tracking echocardiography (Vivid E9, GE) was performed in 50 HCM with preserved LV EF (38 m; 49± 14 y, all LV EF > 55%) and 50 age, gender matched controls (38 m; 49±12 y). The global and segmental longitudinal (LS), circumferential (CS) and radial strain (RS) strains of endocardia (End), mid-wall and epicardia layers were analyzed using a novel layer-specific TTE. The ratio of End to epicardia strain (End/Epi) was calculated.

Results:
The LV EF were similar in pts and controls (64±8 vs 64±7 %, p=0.95). The diastolic function was significantly impaired in HCM pts compared with controls (E/E’:18.4±8.4 vs 8.6 ±2.4, p<0.0001). The absolute value of LS and CS was reserved at apical End layers (-34±7 vs -35±6, p=0.44); the remaining segments and LV global LS and CS of three layers were significantly smaller (LS,-16±5 vs -22±3; CS -24±8 vs -33±7; p<0.0001), and LS and CS End/Epi (1.7±0.3 vs 1.3±0.1, 3.4±1.1 vs 1.7±0.2 respectively, P <0.0001) was significantly higher in HCM pts than in controls. The RS and LV twist were preserved in all LV segments (27±10 vs 24±12, p=0.19; 20±8 vs 18±5, p=0.33; respectively). In HCM pts, the LV LS value at basal and middle levels revealed significant negative correlations with LV relative wall thickness (r=–0.65, –0.59 and –0.60, –0.54, respectively , p< 0.0001); and mild negative correlations (r=-0.33,-0.29, p<0.0001). The LV CS value at all levels revealed mild correlations with relative wall thickness (r=-0.22, p<0.05) . The LS were significantly reduced at the hypertrophic segments (Figure).

Conclusions:
In HCM patients with preserved LVEF, LV GLS was impaired, but apical End LS and basal End CS, LV RS as well as LV twist were maintained as the compensation for reduction LV LS and CS. The Bull’s eye of LS may help us to localize the lesion segments and define the type of HCM.
Abstract 11134: Subclinical Coronary Plaque Burden in Asymptomatic Relatives of Patients With Documented Premature Coronary Artery Disease
Authors: Christiansen Morten K , Jensen Jesper M , Bøtker Hans Erik , Jensen Henrik K
Published: July 2021

Introduction:
A family history of premature coronary artery disease (CAD) is a well-known risk factor for adverse coronary events with age of onset being inversely related to the degree of heritability.

Hypothesis:
We hypothesized that asymptomatic first degree relatives, of patients with premature CAD, suffer a high burden of subclinical coronary atherosclerosis.

Methods:
First degree relatives, aged 30-65 years, of patients with a documented coronary revascularization procedure before the age of 40 years, were invited to participate in the study. Participants were matched by age, sex and absence of a family history, with patients referred for coronary CT angiography (CTA) because of atypical angina or non-anginal chest pain. A pooled blinded analysis was performed.

The main outcome measure was the number of plaque-affected coronary segments.

Results:
88 relatives and 88 symptomatic controls underwent CTA. Treatment of hypertension and dyslipidemia tended to be more common among controls (p=0.06). 4 relatives reported vague symptoms of which none had angiographic signs of obstructive CAD (any luminal stenosis above 50%). The calculated SCORE risk among relatives was generally low (85% having a 10-year risk of ≤1%).

Relatives had significantly (p=0.006) more affected segments than controls (0 segments: 29,6% vs. 48,9%, 1-2 segments: 27,3% vs. 31,8%, 3-5 segments: 23,9% vs. 11,4% and ≥6 segments: 19,3% vs. 8,0%). In a multivariable logistic regression analysis, the presence of any CAD (OR 3.16 (1.50;6.70)) as well as non-calcified plaques (OR 2.2 (1.14;4.26)), mixed plaques (OR 6.77 (2.7;16.98)) and calcified plaques (OR 2.34 (1.01;5.43)) were more frequent. Although increased, the presence of obstructive plaques, however, did not differ statistically significantly between relatives and controls (OR 2.58 (0.85;7.83)).

Conclusions:
Asymptomatic relatives of patients with premature CAD suffer a high coronary plaque burden even when compared with symptomatic patients with an a priori higher risk of CAD. Our results indicate a strong genetic component in the genesis of coronary atherosclerosis and, moreover, underline the limitations of current guidelines on prevention of CAD.
Abstract 11447: Low Incidence of Appropriate Therapy Following Defibrillator Implantation for Primary Prevention of Sudden Cardiac Death in Hypertrophic Cardiomyopathy
Authors: Thavikulwat Amalie C , Tomson Todd T , Knight Bradley P , Bonow Robert O , Choudhury Lubna
Published: July 2021

Introduction:
Hypertrophic cardiomyopathy (HCM) is a leading cause of sudden cardiac death (SCD) in young adults. Implantable cardioverter defibrillators (ICD) effectively terminate ventricular tachycardia (VT) and fibrillation (VF) that cause SCD, but the reported prevalence of and patient characteristics leading to appropriate ICD therapy in HCM have been variable.

Hypothesis:
We hypothesized that some risk factors may be more prevalent than others in patients with HCM who receive appropriate ICD therapy and that the overall incidence of appropriate therapy may be lower than that reported previously.

Methods:
We retrospectively studied all patients with HCM who were treated with ICDs at our referral center from 2000-2013 to determine the rates of appropriate and inappropriate ICD therapies.

Results:
Of 1136 patients with HCM, we identified 135 who underwent ICD implantation (125 for primary and 10 for secondary prevention), aged 18-81 years (mean 48±17) at the time of implantation. The mean follow-up time was 5.2±4.5 years. Appropriate ICD intervention occurred in 20 of 135 patients (2.8%/year) by providing a shock or antitachycardia pacing in response to VT or VF. The annual rate of appropriate ICD therapy was 2.4%/year for primary and 7.2%/year for secondary prevention devices. Commonly used risk factors were equally prevalent among patients who received appropriate therapy and those who did not; furthermore, the likelihood of receiving appropriate therapy in the presence of each risk factor was similar (Figure). Inappropriate ICD therapy occurred in 27 patients (3.8%/year).

Conclusions:
ICDs provide clear benefit to patients who experience life-threatening arrhythmias, particularly those being treated for secondary prevention. However, the appropriate therapy rate for primary prevention was lower than previously reported, and no single risk factor appeared to have stronger association with appropriate ICD therapy than others.
Abstract 11522: Does Neointimal Pattern Predict Instent Thrombus
Authors: Gao Lei , Lee Stephen , Kim Chong-Jin , Minami Yoshiyasu , Ong Daniel S , Soeda Tsunenari , Lowe Harry , Choi So-Yeon , Lerman Amir , Lee Jay , Lee Hang , Uemura Shiro , Jang Ik-Kyung
Published: July 2021

Introduction:
Local determinants of instent thrombus formation after drug-eluting stent (DES) implantation have not been systematically investigated.

Hypothesis:
Certain neointimal patterns assessed by optical coherence tomography (OCT) may represent local surface thrombogenesity after DES implantation.

Methods:
A total of 208 patients with 262 DES who underwent follow-up OCT examination 11 months after DES implantation were studied. The detailed OCT findings including characteristics of neointima, lumen size, and stent morphology were compared between the group with and without thrombus.

Results:
Thrombus was identified in 11.5% (24/208) of the patients. Lipid-laden neointima, thin-cap fibroatheroma, heterogeneous neointima, and extra-stent lumen were more frequently detected in the thrombus group compared to the non-thrombus group (Figure). No difference was found in the % of uncovered (4.9±6.7% vs. 4.2±5.4%; p=0.575) or malapposed struts (1.5±2.5% vs. 0.8±2.1%; p=0.116) between the two groups. Minimal lumen cross sectional area was significantly smaller in the thrombus group compared with the non-thrombus group (2.9±1.7mm
2
vs. 4.6±2.0mm
2
; p<0.001).

Conclusions:
Neointimal morphology and smaller lumen cross-section area are important factors associated with instent thrombus.
Abstract 11548: Nanofibrous Collagen Scaffolds Seeded With Human Pluripotent Stem Cell-derived Cardiomyocytes Induce Cardiac Remodeling in Dilated Cardiomyopathy
Authors: Boitard Solene , Joanne Pierre , Kitsara Maria , Nematalla Hany , Vanneaux Valérie , Pernot Mathieu , Larghero Jerome , Forest Patricia , Chen Yong , Menasché Philippe , Agbulut Onnik
Published: July 2021

Introduction:
Limited data are available on the effect of stem cells in non-ischemic dilated cardiomyopathy (DCM).

Hypothesis:
Since the diffuse nature of DCM calls for a broad distribution of cells, we tested the scaffold-based delivery of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) in a mouse model of DCM.

Methods:
(1) In vitro protocol: A clinical grade atelocollagen was electrospun and crosslinked under different conditions to optimize production of nanofibrous scaffolds. (2) In vivo protocol: The biocompatibility of acellular collagen scaffolds was first tested in C57BL6 (n=24) and αMHCMerCreMerSf/Sf (n=18) mice, a strain in which DCM is induced by a cardiac (αMHC)-specific and tamoxifen(T)-inducible invalidation of serum response factor (SRF). Scaffolds seeded with hiPSC-CM (obtained by a sequential activation/inhibition of the Wnt pathway) or kept acellular (controls) were then implanted in 8 and 6 αMHCMerCreMerSf/Sf mice, respectively.

Results:
As assessed by SEM and shear wave elastography, a 10% citric acid concentration and 150 min of baking at 150°C producing a scaffold with an average fiber thickness of 1400 nm, an average pore size of 2500 nm and an elasticity modulus of 10.1 kPa were associated with optimal hiPSC-CM differentiation and colonization of the scaffold. Seven and 14 days after implantation, the biocompatibility of cell-free scaffolds was confirmed by echocardiography and histology. Scaffolds seeded or not with hiPSC-CM were then grafted in DCM mice. After 14 days, heart function drastically decreased in hearts receiving cell-free scaffolds while it remained stable in the treated mice (p<0.001 for LVEDV, LVESV and EF). This pattern was associated with (1) a significantly (p<0.01) increased genomic and proteomic expression of SRF possibly reflecting an activation of resident stem cells (unaffected by T) and/or an increase in endothelial cells (also T-unaffected), in line with the greater vascularity of the scaffold, and (2) a reduced fibrosis consistent with the upregulation of several genes involved in extracellular matrix remodeling.

Conclusion:
These data suggest that a hiPSC-CM loaded electrospun collagen patch stabilizes function in DCM, most likely through paracrine signaling.
Abstract 11550: Human Mesenchymal Stem Cell-Derived Microvesicles Mitigate Aortic Smooth Muscle Cell Activation via miR-147 and Attenuate Aortic Aneurysm Formation
Authors: Sharma Ashish K , Lu Guanyi , Salmon Morgan D , Gehrau Ricardo C , Mas Valeria R , Weiss Mark L , Ailawadi Gorav , Upchurch Gilbert R
Published: July 2021

Objective:
Mesenchymal stem cells (MSCs) can release microvesicles (MVs) but their effects on aortic aneurysm (AA) formation are unknown. We hypothesize that MSC-derived MVs can inhibit AA formation via modulation of specific microRNAs (miRs).

Methods:
An elastase-perfusion abdominal AA model was used with 8- to 12- week old male mice. The abdominal aorta was perfused for 5 minutes with porcine pancreatic elastase and treated with or without human umbilical cord MSC-derived MVs (1x10
6
given intravenously on day 1). On day14 following perfusion, the abdominal aortic diameter was measured by video micrometry and expressed as percentage increase over baseline. miRNA microarray was performed on aortic tissue using Affymetrix GeneChip hybridization. MVs were transfected with either miR-147b mimic or inhibitor (25nM, Invitrogen, CA) using Lipofectamine RNAiMAX and co-cultured with aortic smooth muscle cells (AoSMCs) followed by treatment with transient elastase (5 minutes) or recombinant IL-17 (10 ng/ml). Cytokines were analyzed in cell culture supernatants after 24 hrs. Groups were compared by ANOVA followed by Bonferroni post hoc test.

Results:
Treatment of elastase-perfused WT mice with MVs caused a significant attenuation of aortic diameter compared to elastase-perfused mice alone (102.4±6 vs. 162.6±17.9% respectively; mean +/- S.E.; n=5, p=0.03). A significant mitigation of pro-inflammatory cytokines (IL-17, HMGB1, MCP-1, TNF-α and KC), inflammatory cell infiltration (CD3+ T cells, macrophages and neutrophils) and decrease in elastic fiber disruption occurred in aortic tissue from elastase-perfused mice treated with MVs compared to elastase-perfused mice alone. miRNA analysis of aortic tissue demonstrated a significant upregulation of miR-147b (10-fold; p<0.001), miR-19a (9-fold; p<0.001) and a downregulation of miR-98 (1.2 fold; p<0.05) in mice with AA compared to controls (n=5 mice/group). Treatment of AoSMCs with elastase or IL-17 induced cytokines (IL-6, RANTES, MCP-1, TNF-α and KC) which were attenuated by co-cultures with MVs transfected with miR-147 inhibitor.

Conclusions:
MSC-derived MVs attenuate aortic inflammation and inhibit AoSMC activation via miR-147 suggesting a novel protective mechanism in AA pathobiology.
Abstract 11552: The α5β1 Integrin Mediates Insulin-like Growth Factor-1 Induction of Aortic Smooth Muscle Alpha-Actin Expression Through a PI3K/mTORC2/eIF4E Translational Mechanism
Authors: Blackstock Christopher , Higashi Yusuke , Sukhanov Sergiy , Delafontaine Patrice
Published: July 2021

In arterial remodeling, smooth muscle cell (SMC) loss of contractile phenotype and increased proliferation may result in vessel stenosis or a greater propensity for aneurysm formation and rupture. Here, we show that insulin-like growth factor-1 (IGF-1) induces contractile phenotype of human aortic SMCs in culture, and we investigate the signal transduction mechanisms responsible using Western blot. IGF-1 induced a dose-dependent increase in protein expression of the contractile marker alpha-actin (αSMA) (2.4-fold-increase, 18hr serum-free vs. 100ng/mL IGF-1, p<0.001), without affecting ACTA2 mRNA levels (real time RT-PCR, 4-18 hrs, p=NS). Moreover, IGF-1 upregulation of αSMA expression was not blocked by actinomycin D but was inhibited by cycloheximide (p<0.01), thereby demonstrating posttranscriptional and translation-dependent regulation by IGF-1, respectively. Furthermore, IGF-1-induced αSMA expression was not blocked with PD98059 or rapamycin (50 or 100 nM), but was completely inhibited with LY294002 (p<0.001), 500 nM rapamycin (p<0.01), and Torin 1, thereby indicating that the ability of IGF-1 to induce SMC differentiation was independent of Erk1/2 and mTORC1, but dependent on PI3K- and mTORC2-signaling. A prolyl-hydroxylase-inhibitor (EDHB) or a function-blocking antibody against the α2β1 integrin (BHA2.1) had no effect on IGF-1-upregulation of αSMA expression. However, both EDHB and BHA2.1 significantly attenuated IGF-1-induced expression of the proliferation marker PCNA, thereby suggesting that collagen and the α2β1 integrin promote IGF-1-induced proliferation. Conversely, a blocking antibody against the α5β1 integrin (JBS5) did not block IGF-1-induced PCNA expression but completely inhibited IGF-1 induction of αSMA expression (p<0.01) and abolished IGF-1-induced phosphorylation of a master regulator of cap-dependent protein translation, eukaryotic initiation factor-4E (eIF4E) (p<0.001). Therefore, we concluded that IGF-1 induced αSMA expression via a PI3K/mTORC2/eIF4E translational mechanism that is dependent on the α5β1 integrin. Overall, these findings provide evidence that the α5β1 and α2β1 integrins mediate IGF-1-signaling to govern IGF-1-induced translational regulation of SMC phenotype.
Abstract 11585: Long-term Survival of Stroke and Acute Delirium Following Cardiac Surgery is Compromised: Validation of a Prediction Model for Neurological Outcomes
Authors: Ariyaratnam Priyadharshanan , Loubani Mahmoud , Vijayan Ajith
Published: July 2021

Introduction:
Neurological complications following cardiac surgery have a high in-hospital mortality and morbidity associated with it. Unlike the USA, the UK does not have a scoring system to predict such complications. Furthermore, little long-term data exists for survival from stoke, transient ischaemic attacks (TIAs) and acute delirium following cardiac surgery. We therefore looked at the long-term effects of neurological complications as well as developed and validated a scoring system to predict post-operative stroke.

Methods:
Retrospective analysis of data collected prospectively on our cardiac database between July 1999 and March 2015. A multivariate logistic regression model was used to create a prediction model and the model was then validated. Long-term survival was evaluated using the Kaplan-Meier method.

Results:
In total, 13,655 consecutive patients underwent cardiac surgery using cardiopulmonary bypass. Permanent stroke occurred in 1.1% of patients, acute delirium in 2.2% and TIAs in 1.1%. The validation for the final logistic regression model for permanent stroke showed a c-index of 0.717. Permanent stroke (38% vs 3%), TIA (6% vs 3%) and acute delirium (8% vs 3%) patients were significantly more likely (p<0.05) to have a higher in-hospital mortality compared to non-neurological complication patients. These neurological complications were significantly more likely to have longer hospital stays and rehabilitation (p<0.05). The long-term survival (2, 5, 10 & 15 years) was significantly less (p<0.05, log-rank) in those who survived stroke, TIA and acute delirium at hospital discharge compared to those discharged who did not sustain these pathologies (Figure 1).

Conclusion:
We have developed a risk score to predict these neurological outcomes which will help identify those patients at the highest risk so they can be thoroughly counselled and optimised pre-operatively and that our annual resource allocation can be planned.