bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 17432: Specific Care Process Implementation Associated With Improved Reperfusion Times Across Multiple STEMI Networks: Insights From The AHA Mission: Lifeline STEMI Accelerator Program
Authors: Fordyce Christopher B , Al-Khalidi Hussein R , Jollis James G , Roettig Mayme L , Bagai Akshay , Berger Peter B , Corbett Claire C , Dauerman Harold L , Fox Kathleen , Garvey J. L , Gu Joan , Henry Timothy D , Rokos Ivan C , Sherwood Matthew W , Wilson B H , Granger Christopher B
Published: March 2022

Introduction:
The STEMI Accelerator Program occurred in 16 U.S. metropolitan regions and resulted in more patients receiving timely reperfusion. We assessed whether implementing key care processes was associated with shorter reperfusion times.

Methods:
Hospitals (n=167 with 23,498 STEMI patients) were surveyed pre- (02/2012) and post- (08/2014) intervention with a standardized care process questionnaire. Survey data were then merged with patient-level clinical data over the same time period. For reperfusion times, hospitals were stratified by whether they implemented a specific process of care, had a pre-existing process, or never implemented the process.

Results:
Uptake of several care processes increased following intervention: pre-hospital activation (62% to 91% of hospitals; p<0.001), single call transfer protocol from an outside facility (45% to 70%; p<0.001) and emergency department (ED) bypass for both direct presenters via paramedics (48% to 59%; p=0.002) and transfer patients (56% to 79%; p=0.001). There were significant differences in median first medical contact-to-device (FMC) times (Figure) among patients treated at hospitals that implemented pre-activation compared to non-implementers (88 min for implementers; vs 89 min for pre-existing; vs 98 min for non-implementers; p<0.001 for group comparisons). Similarly, patients treated at hospitals implementing single call transfer protocols had shorter median FMC times (112 min vs 128 min vs 152 min; p<0.001). ED bypass was also associated with shorter FMC times for both direct presenters (84 min vs 88 min vs 94 min; p<0.001) and transfers (123 min vs 127 min vs 167 min; p<0.001).

Conclusions:
The STEMI Accelerator program increased the uptake of key care processes, which were in turn associated with shorter median reperfusion times. These findings support ongoing efforts to implement regional STEMI networks focused upon pre-hospital activation, single call transfer protocols and ED bypass.
Abstract 17440: Glycemic Variability Inflicts Injury on Non-infarct Area in Patients With Anterior ST-segment Elevation Myocardial Infarction
Authors: Minaimoto Yugo , Iwahashi Noriaki , Gohbara Masaomi , Kataoka Shunsuke , Akiyama Ellchi , Maejima Nobuhiko , Tsukahara Kengo , Hibi Kiyoshi , Kosuge Masami , Ebina Toshiaki , Umemura Satoshi , Kimura Kazuo
Published: March 2022

Background:
Glycemic variability (GV) plays an important role in patients with ST-segment elevation myocardial infarction (STEMI), but the relationship between GV and the strain of left ventricle by cardiac magnetic resonance imaging (CMR) has not been examined.

Methods:
We investigated 55 patients with anterior STEMI who underwent reperfusion therapy within 12h onset. We analyzed GV, as determined by a continuous glucose monitoring system (CGMS; iPro2, Medtronic, Minneapolis, USA), and circumferential strain (CS) of the left ventricule by CMR. All patients were equipped with CGMS in a stable phase after admission. CMR were performed 7days and 7 months repeatedly. We checked CS at each segment as regional function and global CS as global function. Patients were classified into 2 groups according to the mean amplitude of glycemic excurtions (MAGE) that was calculated by measuring the arithmetic mean of the differences between consecutive peaks and nadirs if the differences were greater than 1 standard deviation; high-MAGE group and low-MAGE group.

Results:
There were no significant differences between high-MAGE and low-MAGE group regarding age (63.4±13.0 vs. 64.0±11.6 years) ,male gender (85% vs. 78%). High-MAGE group had more frequently with diabetes (44% vs. 3%, p<0.001), greater peak creatine phosphokinase (CPK; 4619 vs. 2934U/L, p=0.02), lower global CS (-15.4±2.8% vs. -18.1±5.0%, p=0.01) and mid-inferior CS (-16.8±6.6% vs. -20.6±6.7%, p=0.04) at 7 months CMR.

At late CMR, MAGE had significant correlation with global CS (R=0.3, p=0.024) and CS at mid-inferior (R=0.35, p=0.009). Multivariate analysis revealed that MAGE (β=0.35, p=0.009) were independently correlated with CS at mid-inferior, and peak CPK (β=0.398, p=0.003) were independently correlated with global CS.

Conclusion:
GV inflicted injury on non-infarct area after the onset of anterior STEMI. This may be related to left ventricular remodeling.
Abstract 17459: Recurrent In-stent Thrombosis: An Atypical Presentation of Malignancy
Authors: Klein Evan C , Crabbe Deborah L
Published: March 2022

Management of acute coronary syndromes most typically involves percutaneous coronary intervention with or without stent placement, and this has significantly improved morbidity and mortality in this syndrome. However, intra-coronary stents can lose their patency due to either in-stent restenosis or in-stent thrombosis (IST). More rarely recurrent in-stent thrombosis (RIST) can occur.

Here we report the case of a 58 year old African American male with a history of human immunodeficiency virus (on highly active antiretroviral therapy), chronic kidney disease, cerebrovascular accident, chronic obstructive pulmonary disease and tobacco abuse. He presented with 7 non-ST-elevation myocardial infarctions, 6 angiographically documented episodes of coronary artery occlusion and 2 episodes of early in-stent and 2 late in-stent thromboses over the span of less than 7-months. This occurred despite reasonable evidence for compliance with optimal medical therapy. His antiplatelet regimen was changed several times until he presented 1-month after his final IST with gastrointestinal bleeding from a fungating partially obstructing well to moderately differentiated invasive adenocarcinoma in the ascending colon. Unfortunately, he expired 2-months later.

Including our patient there have now been 4 reports of early RIST in patients with undiagnosed malignancy. Specific malignancies reported include: prostate, adrenal, renal, bladder, and now gastrointestinal primaries. Trousseau’s syndrome, the prothrombotic state of malignancy, has long been implicated in both venous and arterial thrombosis. We believe this prothrombotic milieu also increases the risk for in-stent thrombosis.

In the setting of malignancy, as with myocardial infarction, delay before diagnosis can be catastrophic. While more data is needed on the topic, for now we suggest that physicians consider aggressive screening for malignancy in patients with IST or RIST.
Abstract 17499: ETC-1002 Incrementally Lowers Low Density Lipoprotein-cholesterol in Patients With Hypercholesterolemia Receiving Stable Statin Therapy
Authors: Ballantyne Christie M , MacDougall Diane E , Margulies Janice R , Robinson Paula L , Hanselman Jeffrey C , Lalwani Narendra D
Published: March 2022

Background:
ETC-1002 is an oral investigational drug that modulates hepatic adenosine triphosphate-citrate lyase to reduce cholesterol biosynthesis and may be beneficial in treating patients with elevated LDL-C despite using stable statin therapy.
Methods:
A double-blind, parallel group, placebo-controlled multicenter trial evaluated patients (n=134) with baseline LDL-C of 115-220 mg/dL while taking atorvastatin ≤20 mg, simvastatin ≤20 mg, rosuvastatin ≤10mg or pravastatin ≤40 mg randomized to ETC-1002 120 mg, ETC-1002 180 mg, or placebo once daily for 12 weeks.
Results:
ETC-1002 120 mg (p=0.0055) and 180 mg (p<0.0001) lowered LDL-C significantly more than placebo (primary endpoint) as an add-on to statin therapy. ETC-1002 also lowered (p<0.05) apolipoprotein B, non-high density lipoprotein-cholesterol, total cholesterol and LDL particle number more than placebo. C-reactive protein was also reduced with ETC-1002 120 mg (22%, p=0.26) and 180 mg (30%, p=0.08) versus 0% with placebo. Adverse events (AEs), muscle-related AEs, discontinuations due to AEs and levels of clinical safety labs were generally similar compared with placebo.

Conclusion:
In patients with elevated LDL-C despite stable statin therapy, ETC-1002 produces incremental LDL-C lowering and is well-tolerated.
Abstract 17511: Microvesicles and MicroRNAs as Marker of Acute Kidney Injury After Cardiac Surgery in Children
Authors: Mariani Silvia , Sullo Nikol , Jn Tala Maria Teresa , Dott William , Wozniak Marcin J , Chan Danny , Kumar Tracy , Lotto Attilio A , Murphy Gavin J
Published: March 2022

Introduction:
AKI is very common in paediatric cardiac surgery patients. The diagnosis relies on changes in serum creatinine and urine output, which lack specificity and sensitivity especially in newborns and premature infants. Diagnostic changes also occur late in the injury phase when interventions have limited effectiveness. Microvesicles (MV) are small particles (<1μm) in plasma that often contain miRNA. Their levels have been shown to be altered in animal models of AKI where they regulate injury responses.

Hypothesis:
MV and associated miRNA provide specific and early-detection markers for AKI and a tool to investigate AKI pathogenesis.

Methods:
Study subjects were 24 children (<17 yrs), undergoing cardiac surgery with cardiopulmonary bypass (CPB) without pre-existing inflammatory state, AKI or extracorporeal life support. AKI was diagnosed following the KDIGO definition. Blood and urine samples were collected pre-operatively and at 6 and 24 hours. Cytokines were measured on a MAGPIX platform. Leukocyte and platelets activation, and MV derivation was assessed by flow cytometry and NanoSight device. miRNAs were isolated from MV preps and analyzed by RT-PCR using Applied Biosystems kits.

Results:
AKI was diagnosed in 14 patients and was confirmed by urinary NGAL increase at 6 hours after the operation (25±3.45 ng/ml vs 10.44±2.9 ng/ml; p 0.006). Patients with AKI were younger, underwent longer CPB, received higher volumes of red blood cells, and required higher inotrope support (Table). AKI subjects had increased levels of monocyte and B1-integrin MV. That correlated well with IL-8 and MCP-3 levels and monocyte activation. These changes were also reflected in miRNA profile in both groups.

Conclusions:
MV and miRNA could potentially serve as early AKI markers in children and their analysis reveals mechanistic parallels with adults.
Abstract 17523: Improved Rates of Bystander Cardiopulmonary Resuscitation and Survival Consistent Across Socioeconomic Spectrum: Results From the North Carolina HeartRescue Project
Authors: Malta Hansen Carolina , Kragholm Kristian , Pearson David A , Tyson Clark , Dupre Matthew E , Jollis James G , Strauss Benjamin , Anderson Monique L , Fordyce Christopher B , McNally Bryan , VandenHoek Terry , Granger Christopher B
Published: March 2022

Introduction:
Data have shown that out of hospital cardiac arrest (OHCA) patients in lower socioeconomic status (SES) groups have lower rates of bystander intervention and survival. Following the North Carolina HeartRescue project, we explored whether improved rates of statewide bystander cardiopulmonary resuscitation (CPR) and survival are consistent across SES.

Hypothesis:
Statewide efforts have improved both bystander CPR and survival following OHCA irrespective of SES.

Methods:
Using the CARES registry, we identified and geocoded OHCAs from counties with complete case capture from 2010-14 in North Carolina (population 3 million). We divided patients (n=7,220) into tertiles of census-determined neighborhood SES by % with high school degree and median household income.

Results:
Rates of bystander CPR improved significantly irrespective of neighborhood SES level as determined by % with a high school degree or median household income, but remained highest for those with highest SES (Figure). The increase in survival rates significantly differed between SES groups (interaction p<0.05), and the greatest increase was in the lowest tertile: 144% increase for lowest % of high school degree and 66% increase for lowest median household income. The absolute difference in survival between the highest and the lowest tertile decreased from 3.3% in 2010 to 1.8% in 2014 according to % with a high school degree, p for trend 0.001; and from 2.1% to 0.9% according to median household income, p=0.002.

Conclusion:
Following 4 years of the HeartRescue quality improvement program, there were substantial improvements in bystander CPR and survival, which was consistent across socioeconomic status. The greatest increase in survival appeared to be among lower SES. The absolute differences in rates of bystander CPR and survival between the highest and lowest tertiles for neighborhood level of high school degree and median household income appear to have narrowed during this period.
Abstract 17532: Impact of High Hepatic Wedge Pressure, Portal Hypertension, on Hemodynamics and Liver Function in Patients After the Fontan Operation
Authors: Negishi Jun , Ohuchi Hideo , Noritake Kanae , Hayama Yosuke , Sasaki Osamu , Iwasa Tohru , Miyazaki Aya , Sasaki Osamu
Published: March 2022

Background:
Fontan circulation may be, in part, characterized by portal hypertension that can be estimated by hepatic vein wedge pressure (HWP).

Purpose:
To evaluate associations of HWP in cosecutive 318 Fontan patients (18±7 years old) during catheterization and compared the results with the hemodynamics, liver function and the related plasma biomarkers. HWP significantly correlated positively with inferior vena cava pressure (IVCP), pulmonary artery resistance (Rp), ration of Rp to systemic artery resistance (Rs) (Rp/Rs), and cardiac index and negatively with Rs and arterial and mixed venous oxgen saturations. Of those, high IVCP, low Rp and high Rp/Rs were independently correlated with high HWP (p<0.05 for all). As for the liver function, HWP significantly correlated positively with plasma levels of total bilirubin (TB), hyaluronic acid, and type IV collagen (TyIV) and negatively with plasma levels of albumin and cholinesterase (ChE). Of those, ChE, TB and TyIV were independently correlated with high HWP (p<0.01 for all). High HWP, low ChE, and high TyIV significantly correlated with high plasma nitric oxide products (p<0.01).

Conclusion:
High HWP associates with a significant reduction of Rp and Rs with preserved cardiac output. This unique Fontan circulation with Rs-dominant reduction may be due to both portal hypertension and overproduction of nitric oxide secondary to liver dysfunction.
Abstract 17535: Carotid Artery Calcifications and High-risk Carotid Plaques Identified by CT Angiograms are Associated With an Increased Predisposition of Ischemic Strokes
Authors: Carmona Rubio Andres , Adib Keenan , Madam Narasa , Karki Roshan , Gudleski Gregory , Sharma Umesh
Published: March 2022

Introduction:
Ischemic strokes account for nearly 90% of all strokes in the United States. Non-invasive computed tomographic angiograms (CTA) are performed routinely in patients with stroke-like symptoms. While the severity of carotid stenosis is conventionally used to plan medical therapy or interventions, there is no data to predict the future risk of ischemic strokes based on additional high-risk characteristics that can be visualized by modern CTA.

Methods:
We examined the head and neck CTA of 485 patients who presented to our tertiary stroke center with symptoms suggestive of transient ischemic attacks or stroke. Using the post-processed CT images, we analyzed the severity of stenosis and plaque characteristics of the common, internal and external carotid arteries, and also evaluated for evidence of ischemic strokes. Carotid lesions were defined in terms of the degree of stenosis, calcifications (speckled or eccentric), presence of non-calcified plaques, positive remodeling, and presence of a Napkin-Ring Sign.

Results:
Of the 485 patients, 278 were males (mean age: 67 years), with 109 having a history of stroke. Our data showed that patients with unilateral or bilateral high-risk soft plaques and carotid calcifications visualized by CTA were associated with increased risk of ischemic cerebral events (p<0.001). Additionally, we found that patients with stroke had a greater number of calcium speckles (6-speckles in stroke group vs 4-speckles in non-stroke group; P<0.01) in their carotid arteries. Receiver-Operating Curve analysis showed that the presence of more than 2 speckles in the carotid arteries portends a higher likelihood of developing a stroke (P<0.01).

Conclusions:
This novel study shows that the presence of carotid artery calcifications or non-calcified high-risk soft plaques on one or both carotid arteries, in addition to >2 calcium speckles in the carotid arteries were associated with an ischemic stroke. These results emphasize that the nature of atherosclerosis, and utility of comprehensive non-invasive CTA to identify patients who are at higher risk of developing ischemic stroke with a goal of early therapeutic strategies.
Abstract 17559: Norepinephrine Levels are Associated With the Magnitude of Vasoconstriction During Mental Stress
Authors: Alkhoder Ayman , Isakadze Nino , Obideen Malik , Vaccarino Viola , Bremner J. Douglas , Pearce Brad D , Chou Danielle , Raggi Paolo , Wilmot Kobina , Al Mheid Ibhar , Long Qi , Abdelhadi Naser , Kutner Michael , Quyyumi Arshed , Shah Amit
Published: March 2022

Background:
Patients with CAD develop varying degrees of microvascular vasoconstriction in response to mental stress, leading to myocardial ischemia. Catecholamine increases during mental stress may explain this effect. We hypothesized, in a cohort of stable CAD patients, that increased epinephrine and norepinephrine levels from rest to peak mental stress predict peripheral microvascular vasoconstriction.

Methods:
We analyzed data from 204 patients with CAD and high quality vascular data. Subjects underwent a standardized mental stress test using a public speaking task. Peripheral arterial tonometry (PAT) was used to assess peripheral microvascular function during rest and mental stress. The PAT response was calculated as a ratio of the minimum pulse wave amplitude during the speaking task to the mean amplitude during rest. Plasma epinephrine and norepinephrine levels were obtained 15 minutes before and at peak mental stress. Linear regression modeling was used to adjust for potential confounders.

Results:
The mean (SD) age was 64 (8), 16% were women, and 28% were African American. Subjects in the quartile with the greatest vasoconstriction had the highest increase in norepinephrine levels (73.5 (31.4) ng/mL [mean (SEM]), while those in the quartile with the least vasoconstriction had decreased norepinephrine levels by 47.7 (32.5) ng/mL, p for trend<0.001 (Figure). There was no significant association between PAT and epinephrine. After multivariable adjustment for sociodemographics, CAD risk factors, medical history, medication use, major depression, and PTSD, the association between the PAT ratio and norepinephrine remained significant (p=0.003).

Conclusion:
Changes in circulating norepinephrine, but not epinephrine levels predict peripheral microvascular vasoconstriction during mental stress.
Abstract 17570: Therapeutic Impact of Autophagy-inducing Peptide on Pressure Overload-induced Heart Failure
Authors: Shirakabe Akihiro , Ikeda Yoshiyuki , Zai Peiyong , Saito Toshiro , Sadoshima Junichi
Published: March 2022

Tat-Beclin1 (TB1), which binds human immunodeficiency virus-1 Nef, is a potent inducer of autophagy. We investigated the therapeutic potential of TB1 in the heart during pressure overload (PO). At baseline, treatment of cardiomyocytes (CMs) with 25 μM TB1 significantly increased both GFP/RFP double positive (Yellow) LC3 puncta (8.3±1.1 vs 1.4±0.2, P<0.05) and RFP LC3 puncta (4.2±1.1 vs 1.5±0.3, p<0.05) compared to treatment with Tat-scrambled (TS). After treatment for 2 weeks with TB1 or TS at 20 mg/kg daily, GFP-LC3 puncta were significantly increased in mouse hearts with TB1 compared to those with TS, with (31.6±5.0 and 20.3±5.9, p<0.05) or without chloroquine (21.7±4.3 and 8.1±2.2, p<0.05), indicating that TB1 stimulates autophagy in the heart. We investigated whether lysosomal clearance of mitochondria, reflecting mitochondrial autophagy, is stimulated by TB1, using Mito-Keima. Puncta with a high ratio of excitation at 560/440 nm co-localized with Alexa 488 Dextran, reflecting lysosomal localization of Mito-Keima, were significantly increased after TB1 compared to after TS treatment (5.68±1.18 vs 1.37±0.76, p<0.05). In order to evaluate the effect of TB1 upon the heart during PO, C57BL/6J mice were subjected to i.p. injections of TB1 or TS for 2 weeks, and the mice were sacrificed after 1 week. Ejection fraction (EF) was maintained (78.3±1.2 vs 63.3±3.0, p<0.05), lung weight/tibial length was lower (7.9±0.3 vs 8.2±0.2, p<0.05), the pressure gradient was greater (89.3±4.4 vs 71.8±4.3, p<0.05), and the end diastolic pressure (EDP) was lower (8.2±0.9 vs 11.5±1.5, p<0.05) in TB1- than in TS-treated mice. Mitochondrial ATP production was better preserved in TB1- than in TS-treated mice (1.72±0.16 vs 1.00±0.16, p<0.05). Mitochondrial DNA content (0.54±0.05 vs 1.00±0.11, p<0.05) and the Cox1 level in mitochondria (0.47±0.11 vs 1.00±0.18, p<0.05) were lower in TB1- than in TS-treated mice, consistent with increased degradation of mitochondria. In EM analyses of the mouse heart, autophagosomes containing mitochondria were observed after TB1 treatment, but not TS treatment. These results suggest that TB1 induces general autophagy and mitophagy in the heart and acts protectively against cardiac dysfunction after PO.
Abstract 17596: Readmissions After Adult Congenital Heart Surgery: Frequency and Risk Factors
Authors: Kim Yuli , He Wei , MacGillivray Thomas , Benavidez Oscar J
Published: March 2022

Introduction:
Readmissions after adult cardiac surgery is an important clinical outcome. Despite case complexity, 30-day readmission after adult congenital heart surgery (CHS) has been under studied.

Hypothesis:
Readmissions after adult CHS are common. There exist identifiable risk factors for unplanned readmission.

Methods:
We obtained State Inpatient Databases for Washington, New York, Florida, and California 2009-2011 and selected admissions 18 - 49 years with ICD-9 CM codes indicating adult CHS. We defined readmission as any non-elective hospitalization for a given patient < 30 days of discharge from the index CHS admission. We examined patient demographic and clinical variables and defined complications using the Society of Thoracic Surgeons Congenital Heart complication short list. Case complexity was grouped using the Risk Adjustment for Congenital Heart Surgery-1 (RACHS-1) categories. High resource use (HRU) admissions were defined as those > 90
th
percentile for total hospital charges. Multivariate analyses using generalized estimating equations were performed to identify adjusted risk factors for readmission.

Results:
Of 9860 admissions, there were 1675 readmissions (17%). Median length of stay for readmissions was 4 days and mortality rate 2.1%. Most common indications for readmission were cardiac (pericardial disease, atrial fibrillation, heart failure) and infectious (endocarditis, post-operative infection). On multivariable analysis, black race (adjusted odds ratio [AOR] 1.2 p<0.04), renal insufficiency (AOR 1.8 p<0.001), drug abuse (AOR 1.4 p=0.001), obesity (AOR 1.2 p=0.03), government-sponsored insurance (AOR 1.3 p<0.001), median income <$40,000 (AOR 1.3 p=0.001), index admissions with complication (AOR 1.1 p=0.04), RACHS-1 3 complexity (AOR 1.3 p=0.04), HRU (AOR 1.4 p=0.003), and emergent (AOR 1.5 p<0.001) were risk factors for readmission.

Conclusions:
One out of 6 adult CHS hospitalizations result in unplanned readmission. Lower socioeconomic status, black race, renal failure, obesity, drug abuse, HRU, emergent index admission, and complications are risk factors for subsequent unplanned 30-day readmission. These risk factors may serve as potential quality improvement targets to reduce readmissions.
Abstract 17599: Medicare Beneficiaries With Indicators of Statin Intolerance Have Increased Coronary Heart Disease Risk
Authors: Muntner Paul , Kent Shia T , Colantonio Lisandro D , Rosenson Robert S , Monda Keri L , Huang Lei , Bittner Vera , Manthripragada Angelika
Published: March 2022

Introduction:
Statin intolerance has been reported to occur in 5% to 20% of patients initiating therapy. There are few data on coronary heart disease (CHD) and mortality risk among patients with statin intolerance.

Hypothesis:
Patients with indicators of intolerance to treatment will have higher myocardial infarction (MI), CHD-related hospitalization and all-cause mortality risk compared to those with high adherence to statins.

Methods:
Using a 5% Medicare sample, we conducted a retrospective cohort study of patients with a history of CHD initiating statins between 2007 and 2011. Statin intolerance was defined as switching from statins to ezetimibe, down-titrating statins with ezetimibe initiation, ezetimibe monotherapy, having a rhabdomyolysis or antihyperlipidemic event claim followed by statin down-titration or discontinuation, statin down-titration or switching between 3 or more types of statins over the first year following statin initiation. High adherence was defined as proportion of days covered with statins ≥80% over the year following initiation using Medicare Part D claims. Patients were followed for MI, CHD-related hospitalization and mortality.

Results:
Among 51,169 Medicare beneficiaries with CHD initiating statins, 21,818 (42.6%) maintained high adherence to statins and 3,978 (7.8%) met the definition for statin intolerance. Over a median of 2.1 years of follow-up, the incidence of MI for those with statin intolerance and high adherence to statins was 17.9 (95% CI 15.1-20.7) and 15.2 (95% CI 14.1-16.3) per 1,000 person-years and CHD-related hospitalization was 43.1 (95% CI 38.7-47.5) and 35.4 (95% CI 33.6-37.1), respectively. After adjustment for demographics, co-morbid conditions, and the Charlson co-morbidity score, the hazard ratio for MI comparing patients with indicators of statin intolerance to those with high statin adherence was 1.22 (95% CI: 1.02-1.45) and 1.20 (95% CI 1.07-1.35) for CHD-related hospitalization. In contrast, statin intolerance was not associated with increased mortality risk (hazard ratio 0.99; 95% CI 0.91-1.07).

Discussion:
Patients with indicators of statin intolerance have an increased risk for MI and CHD-related hospitalization. Approaches are needed to reduce CHD risk in these patients.
Abstract 17632: STIM1 Increases Calcium Stores in the Sarcoplasmic Reticulum of Adult Feline Ventricular Myocytes
Authors: Troupes Constantine , Kubo Hajime , Mohsin Sadia , Berretta Remus , Soboloff Jonathan , Houser Steven
Published: March 2022

Background:
STIM1 is a Sarcoplasmic Reticulum (SR) membrane resident protein implicated in sensing and maintaining SR Ca
2+
levels. The role of STIM1 in the regulation of SR Ca
2+
stores in the normal and diseased heart is not well described. Previous reports confirm that STIM1 is present at low levels in the healthy adult heart, but expression levels increase after cardiac injury.

Objective:
To determine if increased STIM1 expression after cardiac injury may be involved in the disturbed Ca
2+
cycling present within diseased cardiomyocytes.

Results:
Adenovirus was used to express either STIM1 or red fluorescent protein (RFP) in freshly isolated adult feline ventricular myocytes (AFMs). We found that in normally quiescent myocytes, STIM1 induced high resting SR Ca
2+
load and induced Ca
2+
sparks, which lead to spontaneous contractions by triggering action potentials. Concurrently, pacing of AFMs revealed STIM1 also increased fractional shortening and Ca
2+
transient amplitude. However, STIM1 also induced cell death (60% versus only 5% in RFP controls). Blockade of the L-type Ca
2+
channel (LTCC) with verapamil rescued the cell death caused by STIM1, but was unable to reduce SR load or Ca
2+
sparks. In contrast, inhibition of ORAI channels using BTP2 rescued cell death and abolished Ca
2+
sparks, while canonical transient receptor potential channel inhibition had no effect. STIM1 expression reduced baseline LTCC current amplitude by 20%, but there was no difference in current amplitude after Bay K8644 addition, suggesting channel number was not altered.

Conclusions:
STIM1 induced Ca
2+
influx can load the SR of large mammalian myocytes, causing Ca
2+
sparks and waves that can trigger action potentials. The induced APs lead to cell death and this effect could be blocked LTCC blockade. STIM1-mediated Ca
2+
influx was dependent on ORAI channel function. Similar to previous reports, we found that STIM1 reduced LTCC current but did not alter LTCC availability. These data show that after cardiac injury, STIM1 and ORAI may provide Ca
2+
influx that positively influences contractility but negatively impacts cell survival and arrhythmias.
Abstract 17671: TCF21 Regulates Coronary Artery Disease Causing Aryl-hydrocarbon Receptor Gene Expression and its Downstream Pathway Activation by Environmental Ligands
Authors: Kim Juyong B , Pjanic Milos , Sazanova Olga , Wang Tina , Miller Clint , Quertermous Thomas
Published: March 2022

Background:
Recently, the TCF21 gene was linked to the highly replicated coronary artery disease (CAD) associated polymorphism in the 6q23 locus. TCF21 is especially compelling as a causal gene since it is a transcription factor that is known to play a critical role in the development of coronary arteries. One downstream target gene identified through preliminary studies was AHR. AHR is a ligand-activated transcription factor that mediates the cellular response to environmental contaminants, including dioxin and polycyclic aromatic hydrocarbons (eg. cigarette smoke), and has recently been associated with CAD in mice and humans. We set out to identify the TCF21 downstream pathways that are related to CAD.

Methods:
We performed chromatin immunoprecipitation sequencing (ChIP-Seq) and RNA-sequencing using primary human coronary artery smooth muscle cells (HCASMC) to survey the targets of TCF21 binding and the regulated downstream pathways. The peaks from ChIP-Seq were identified using MACSv2 according to ENCODE parameters. RNA-Seq was analyzed using
edgeR
to identify the differentially expressed genes. The effect of TCF21 on Aryl-hydrocarbon receptor (AHR) pathway activation was tested using knockdown and overexpression lentivirus transduction of HCASMC followed by 2,3,7,8-Tetrachlorodibenxo-
p
-dioxin (TCDD) treatment and qPCR.

Results:
RNA-Seq studies identified AHR as a significantly regulated mRNA downstream of TCF21 (p=1.4x10
-5
). Also, the ChIP-Seq identified multiple TCF21 binding peaks in the AHR gene. We found a significant overlap of the AHR and TCF21 binding peaks (p<1x10
-15
) and genes differentially regulated by TCF21 and AHR (p=1x10
-5
), among publicly available datasets. Furthermore, we found that the TCF21 level modulated the magnitude of the ligand-dependent activation of AHR pathway genes by TCDD.

Conclusion:
We identified a novel interaction between TCF21 and AHR, a gene involved in environmental xenobiotic response that was recently associated with CAD. The functional link between TCF21 and AHR provides an opportunity to explore gene by environment interactions in the pathogenesis of CAD.
Abstract 17725: Improved Discriminatory Power to Predict Early LVAD Mortality: The Mechanical Circulatory Support Network Risk Score
Authors: Tchantchaleishvili Vakhtang , Maltais Simon , Haglund Nicholas A , Davis Mary E , Cowger Jennifer A , Shah Palak , Aaronson Keith D , Pagani Francis D , Dunlay Shannon M , Stulak John M
Published: March 2022

Introduction:
Various risk models have been used to predict mortality after implantation of continuous-flow ventricular assist devices (CF-VADs). Discriminatory power and predictive accuracy vary, and there is a need to develop and validate a contemporary risk score in a large multicenter patient cohort.

Hypothesis:
We sought to develop an early mortality risk score utilizing a large voluntary research registry of patients implanted with CF-VADs, with the focus on increased discriminatory power.

Methods:
From May 2004 to May 2015, 1150 patients in the Mechanical Circulatory Support Research Network (MCSRN) registry were randomly divided into equal-sized derivation and validation samples (n=575, each group). Candidate predictors from the derivation sample were subjected to backward stepwise logistic regression until the model with lowest Akaike information criterion value was identified for predicting 90-day mortality. A risk score was developed based on the variables and their respective regression coefficients in the final model. Discriminatory power of the risk score was evaluated using receiver operating characteristic analysis, and calibration was assessed using Hosmer-Lemeshow goodness of fit test.

Results:
Overall 90-day mortality was 9.4% (n=99). The final logistic regression model consisted of 9 predictors: Age at implant, preoperative mechanical ventilation, serum total bilirubin, hemoglobin, tricuspid valve regurgitation severity, left ventricular end-diastolic diameter, cardiac index, pulmonary capillary wedge pressure, and destination therapy (DT) as an indication for pump placement. The area under the curve was 0.86 in the derivation sample (95% CI, 0.75-0.97) and 0.75 in the validation sample (95% CI, 0.63-0.86). Hosmer-Lemeshow goodness of fit test yielded insignificant values in both samples (p=0.75, p=0.58) consistent with good calibration.

Conclusions:
The proposed 90-day mortality MCSRN risk score provides highest-to-date discriminatory power when compared to already published models. The risk score is applicable to a contemporary large cohort of patients implanted with CF-VADs for either indication (bridge or DT).
Abstract 17760: Maintaining High Quality CPR With an Integrated Manual/Mechanical Resuscitation Protocol
Authors: Irisawa Taro , Vadeboncoeur Tyler , Hypes Cameron , Silver Annemarie , McDannold Robyn , Mullins Margaret , Spaite Dan , Bobrow Bentley
Published: March 2022

Background:
High quality manual chest compressions (CC) can be achieved on scene during resuscitation of cardiac arrest patients, but manual CC quality can deteriorate during patient extrication and transport. The purpose of this study was to describe the effect on CC quality of an integrated manual/mechanical chest compression protocol developed to maintain CC quality and patient/provider safety throughout resuscitation.

Methods:
CC quality was monitored using a monitor with accelerometer-based CC sensing (E Series/X Series, ZOLL Medical) during the treatment of consecutive out-of-hospital cardiac arrest patients between 3/1/2013-4/30/2015. The EMS agency performed manual CC guided by real-time audiovisual feedback on scene but deployed the AutoPulse load-distributing band CC device (LDB, ZOLL Medical) in a choreographed manner for extrication and transport. The LDB was also placed prophylactically on patients after ROSC. Descriptive statistics are reported as median (IQR).

Results:
A total of 71 OHCA patients were treated (median age 58 yrs, 66 % male) of which 39 received only manual CC and 32 received both manual and LDB CCs (22 with LDB deployed during ongoing manual CC and 10 with LDB placed after ROSC). With real-time CC feedback, high quality CCs were performed [depth 2.38 in (2.17-2.64), rate 100.3 cpm (99.2-102.5), CC fraction 87.0% (83.8-89.5)]. For patients requiring transport, the LDB was started after 14.2 min (11.6-19.2) of manual CC and was placed with minimal interruptions- total of 27.5 sec (23-42) pause time in 2 minutes prior to LDB deployment. During transport, CC fraction remained high (91.7%; 89.3-95.4) with use of LDB. Seven of 10 patients prophylactically placed on the LDB rearrested, 3 rearrested during transport.

Conclusion:
A choreographed and rehearsed integrated chest compression protocol featuring both manual and mechanical compressions, allows for high quality resuscitation with minimal compression interruptions. Placement of a mechanical device on patients after ROSC may be beneficial as over two-thirds of patients in this study rearrested, one-third of which occurred during transport when delivery of manual compressions is difficult and potentially dangerous.
Abstract 17765: A Meta-analysis of Outcomes at Two and Five Years After the Conclusion of Randomised Controlled Trials of Statin Therapy
Authors: Fulcher Jordan , O'Connell Rachel , Gebski Val , Keech Anthony
Published: March 2022

Introduction:
We examined the long term outcomes for patients in randomised statin trials to investigate if benefits are maintained from on-trial statin therapy

Methods:
Using published time to event outcome data for statin and control arm participants with long term observational follow-up, we performed inverse variance meta-analyses of derived hazard ratios at trial end, two years post trial and five years post trial for mortality outcomes, major coronary events and incident cancer.

Results:
Long term follow-up data was available for patients for various endpoints from eight statin vs control trials (Table 1). Where reported, similar proportions of patients from each trial arm used statin therapy after trial end. Combined results showed significant reductions in the risk of all-cause mortality, cardiovascular mortality coronary mortality and major coronary events for patients in the statin arm at trial end. For three trials, benefits of prior statin therapy on total mortality five years post trial appeared greater than at study close whereas they remained similar or slightly smaller among the other four trials. In combination the majority of the accrued trial benefits appeared preserved at two years post trial and five years post trial, with the magnitude of risk reduction being only slightly smaller over this time. No effect was observed on the risk of cancer at any timepoint (Table 2).

Conclusions:
Participants allocated statin therapy in randomised trials maintained cardiovascular and mortality benefits for at least five years after trial end.
Abstract 17786: Epinephrine Administration (EA) During Cardiopulmonary Resuscitation (CPR) Increases Cerebral Tissue Oxygen Saturation: Study With Pulse-observing Mode of Near-infrared Spectroscopy
Authors: Kano Hitoshi , Saito Tomoyo , Bando Keisuke , Matsui Toshihisa , Endo Akio , Sakurai Keisuke , Katsumi Norifumi , Nagama Masaki , Sageshima Hisako , Takauji Shuhei , Homma Yoshinori , Dannoura Yutaka , Komatsu Hiroshi , Matsui Yutaka , Makino Takao , Makise Hiroshi
Published: March 2022

Introduction:
Recently, the effectiveness of the EA during CPR has been questioned. For some time, we have been analyzing the cerebral tissue oxygen saturation observed during CPR. During AHA 2014, we reported the possibility that an increase in the cerebral tissue oxygenation index (TOI) would predict the recovery of spontaneous circulation (ROSC). This time, we report the results of our clinical study about the relationship between the EA and changes in TOI.

Methods:
In 59 patients undergoing out-of-hospital cardiac arrest, the blood pulsation waveform and TOI in the brain were continuously monitored with the NIRO-200NX system (Hamamatsu Photonics K.K., Japan) using its pulse-observing mode (NIRO-Pulse mode). The total number of EAs was 86 and, as shown in the figure, the initial and terminal TOIs in the CPR before EA (2 minutes) and the initial and terminal TOIs in the CPR after EA (2 minutes) were measured.

Results:
The initial and terminal TOIs before EA were 37.6±7.2% and 40.0±7.2% respectively, and the increase in TOI during the CPR (αTOI) was 2.4±3.4%. On the other hand, the initial and terminal TOIs after EA were 37.6±6.6% and 44.0±8.4% respectively, and the αTOI was 6.5±4.8%.

Discussion:
Since the observation of blood pulsation is not possible with conventional cerebral oxygenation monitors, the relationship between the administration of CPR and changes in cerebral tissue oxygen saturation has not been made clear. However with the NIRO-Pulse mode, the changes in TOI caused by CPR are clearly observed. And, our observation that the terminal TOI and αTOI in the CPR after EA were significantly higher than those before EA suggests that cerebral tissue oxygen saturation is improved by EA. On the other hand, the increase in TOI caused by EA (αTOI) has a certain variation, which suggests the most effective time to administer epinephrine would exist and its effects would differ depending on each patient.
Abstract 17796: Toll-like Receptor 9 Signaling Pathway Ameliorates Cardiac Rupture After Myocardial Infarction by Promoting the Proliferation of Myofibroblasts
Authors: Omiya Shigemiki , Omori Yosuke , Nishida Kazuhiko , Shah Ajay , Otsu Kinya
Published: March 2022

Background:
Toll-like receptor (TLR) 9 signaling pathway plays an important role in inflammatory responses in failing hearts in response to pressure overload and in the pathogenesis of heart failure. However, the role of the signaling pathway in left ventricular (LV) remodeling after myocardial infarction, where necrotic cardiomyocyte death is prominent, has not been elucidated.

Methods and Results:
Wild-type (WT) (n=9) and TLR9 knockout (KO) mice (n=11) were subjected to the left coronary artery ligation to induce myocardial infarction (MI). The survival ratio 7 days after MI was significantly reduced in KO mice (36.4%) than in WT mice (88.9%) (p<0.05). All of dead mice in both groups exhibited cardiac rupture. The peak time occurring rupture was 4 days after MI. The ischemia area at risk, identified by a lack of Evans blue staining were not significantly different between the WT and KO hearts (29.7% and 28.9%). Cardiovascular MRI imaging perfomed at 3 days post MI showed no difference in infarct size, LV volume and ejection fraction between WT and KO mice. The mRNA expression levels of inflammatory cytokines including IL-6 and TNFα were not significantly different in KO mice compared with WT mice. Immunohistochemical analysis did not show the significant difference in the extent of neutrophilic infiltration (CD45 positive cells) and macrophage accumulation (CD68 positive cells) in the infarct region between WT and KO mice. The number of myofibroblasts (αsmooth muscle action-positive cells), one of the cellular components in the formation of granulation tissue, was significantly reduced in KO mice (346 cells /mm2) compared to WT mice (1547 cells /mm2) (p<0.05). The number of myofibroblasts exhibiting Ki-67 immunoreactivity was also markedly lower in KO mice (113 cells /mm2) than in WT mice (789 cells /mm2) (p<0.05), indicating that the proliferative activity of myofibroblasts was significantly decreased in the infarcted regions of KO hearts.

Conclusions:
TLR9 signaling pathway is not involved in inflammatory responses in the infarcted regions of MI hearts but ameliorates cardiac rupture after MI by promoting the proliferation of myofibroblasts.
Abstract 17798: Statin Persistence After Reported Adverse Reactions and Patient Outcomes
Authors: Zhang Huabing , Plutzky Jorge , Shubina Maria , Turchin Alexander
Published: March 2022

Evidence suggests that many patients tolerate statin therapy after an adverse reaction. However, clinical outcomes of statin persistence after adverse reactions are unknown.

We conducted a retrospective cohort analysis of the relationship between persistent statin therapy during 12 months after an adverse reaction, and cardiovascular (CV) events (myocardial infarctions and strokes) and death from any cause. We studied patients in primary care practices at two academic medical centers who reported an adverse reaction to a statin between 2000 and 2011 and were subsequently followed for at least 12 months. Adverse reactions to statins were identified using a combination of natural language processing of provider notes and EMR data.

Among 28,279 study patients, 19,997 (70.7%) had persistent statin therapy after an adverse reaction. There were 10,203 (36.1%) patients at high CV risk (previous history of coronary artery disease (CAD), stroke or diabetes). Over a mean of 1,333 days of follow-up, 2,390 (8.45%) of patients suffered a CV event and 1,354 (4.8%) patients died.

In univariate analysis, among patients at high CV risk 25.7% of patients who stopped statins reached composite primary outcome (CV event or death) vs. 19.6% of patients who had persistent statin therapy (Figure; p < 0.0001). In multivariable analysis adjusted for demographics, smoking status, Charlson Comorbidity Index, family history of stroke or CAD, blood pressure, body mass index, LDL cholesterol level, and renal function, persistent statin therapy was associated with a hazard ratio for primary outcome of 0.887 (95% CI 0.807 - 0.976; p=0.014). Persistent statin therapy was not associated with increased time to primary outcome in either univariate or multivariable analysis among patients with low baseline CV risk.

Persistent statin therapy after a reported adverse reaction to a statin was associated with longer time to CV event or death in patients at high but not low CV risk.
Abstract 17821: Night Time In-hospital Cardiac Arrest Impairs Good Neurological Survival in a Swiss Teaching Hospital
Authors: Marengo Luca , Ummenhofer Wolfgang , Gerster Pascal , Harm Falko , Lüthy Marc , Zürcher Mathias
Published: March 2022

Introduction:
Cardiac arrests (CA) occurring at night have been shown to be associated with lower survival rates for both out-of-hospital and in-hospital resuscitation. There is only scarce information available for Switzerland. We monitored “Rapid Response Team” (RRT) missions at our teaching hospital after implementation of the AHA 2010 guidelines. Survival data for in-hospital cardiac arrest (IHCA) were investigated depending whether the event occurred during the day or at night.

Methods:
A standardized extended in-hospital Utstein data set of all RRT-interventions at the University Hospital Basel, Switzerland, from December 13, 2010 until March 31, 2015 was consecutively collected and recorded in Microsoft Excel (Microsoft Corp., USA). Data were analyzed using IBM SPSS Statistics 22.0 (IBM Corp., USA) and are presented as descriptive statistics.

Results:
RRT was activated for 636 patients, with 459 having a life-threatening status (72%; 33 missing). 270 patients (59%) suffered IHCA. 92 CAs (34%) occurred during the night-shift (23:00 - 06:59), and 177 CAs (66%) occurred during day-shifts (07:00 - 22:59; 1 case with “time data” missing).

Shockable rhythms and witnessed CA were found more often at day- compared with night-time: 34 (20%) vs. 8 (9%; p=0.032) and 133 (77%) vs. 55 (62%; p=0.009), respectively. There was no difference between day and night regarding first-responder chest compressions before RRT arrival. Patients whose IHCA occurred during the day showed more favorable neurological outcomes (Cerebral Performance Categories (CPC) of 1+2: 47 (28%) vs. 15 (17%; p=0.048)). Return of spontaneous circulation (ROSC) and hospital discharge were not different. The time to reach the CA patient was not different (123 s for first responder, 245 s for the complete team).

Conclusions:
IHCA occurring at night show a less favorable neurological outcome than during day time at a Swiss university hospital. A lower rate of shockable rhythms may be a sign of delayed recognition of CA during nighttime, which may be an explanation for the reduced CPC-score.