bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 19733: Long Term Outcomes of 78,808 Patients Undergoing Valve Heart Surgery in a Middle-income Country
Authors: Xavier Regina M , Azevedo Vitor M , Godoy Paulo H , Migowski Arn , Ribeiro Antonio Luiz P , Chaves Rogerio B , Tura Bernardo R , Santos Braulio , Correia Marcelo G , Xavier Carolina A , Hashimoto Lucas A , Weksler Clara , Souza e Silva Nelson A
Published: March 2022

Background:
The outcomes of heart valve surgery (HVS) are unknown in middle-income countries.

Objectives:
To analyze in-hospital and survival of HVS from 2001 to 2007 in Brazil.

Methods:
This is a retrospective observational study of 78,806 patients. Two national databases were used, the Hospital Information System and the Mortality Information System. Kaplan-Meier and log-rank tests were performed. The outcome measures were in-hospital mortality and all-cause mortality during follow-up. These measures have been obtained by probabilistic record linkage of the databases.

Results:
The maximum and median follow-up was 7.7 and 2.8 years. Sex distribution was similar. Median age was 50.0 (35.9 - 62.5). Valve replacement (VRp) accounted for 69.1%. The most common valve injury was mitral stenosis with 38.9%, and was rheumatic heart disease (RHD) in 94.7%. The median age in RHD was lower (44.2) than in the remaining cohort (57.5) (p<0.001). In-hospital mortality was 7.6%. It was higher for females (7.8% versus 7.3% - p<0.001), for concomitant CABG patients (14.6%; p<0.001), and for the elderly (18.42%; p<0.001). Overall survival was 69.9% at the end of the follow-up time. Survival by sex at the year 1 and 5 were respectively, for female 85.0% and 76.5%, for male 84.2% and 72.5%. At the end of the first and fifth year of follow-up time, the survival rates of the age ≥80 group and 20 and 39 years group were respectively 64.7%, and 46.4%, against 91.5% and 85.1%. Survival for concomitant CABG at year 1 and year 5 of follow up were 72.1% and 58.1% and for those who underwent solely HVS, 85.9% and 76.0%, respectively. Concomitant CABG showed increased risk (HR 1.3123, CI95%1.2271 - 1.4033, p<0.0001), and age contributed as secondary increasing factor (HR 1.0216, CI95% 1.0203 - 1.0229, p<0.0001). In non-concomitant CABG, patients submitted to valve repair compared with VRp or multiple surgeries showed a reduced risk (HR 0.6937, CI95%0.6296 - 0.7645, p<0.0001), but age contributed as secondary increasing factor in this set (HR 1.0209, CI95%1.0195 - 1.0222, p<0.0001).

Conclusions:
The magnitude of RHD in Brazil is still great. In-hospital mortality and survival of HVS were less satisfactory compared to those reported in high-income countries.
Abstract 19755: A More Accurate Automatic Cuff Blood Pressure Measurement Method
Authors: Liu Jiankun , Cheng Hao-Min , Chen Chen-Huan , Sung Shih-Hsien , Hahn Jin-Oh , Mukkamala Ramakrishna
Published: March 2022

Most automatic cuff blood pressure (BP) measurement devices are based on oscillometry. These devices compute BP from the envelope of the oscillometric cuff pressure waveform using fixed-ratios. The fixed-ratio values are derived from population averages. As a result, the devices are often inaccurate in patients with stiff arteries. Our hypothesis is that oscillometry can be made more accurate in this important patient population by physical modeling of the phenomenon. We studied 126 patients (ages 38-85, 97 males) referred for diagnostic cardiac catheterization at the Taipei Veterans General Hospital under IRB approval. We obtained oscillometric cuff pressure waveforms for analysis using a commercial device (Omron VP1000 or Microlife WatchBP Office) and reference BP waveforms via an invasive catheter in the opposite brachial artery. We recorded these waveforms before and after sublingual nitroglycerin in many of the patients. We divided the data into a training set comprising 57 of the patient records and a testing set consisting of the remaining 69 patient records. We used the training dataset to develop a method to compute BP from the oscillometric cuff pressure waveform based on a physical model. In contrast to existing devices, the model-based method simultaneously determines BP and the arterial stiffness of the patient. In this way, the method is patient-specific rather than population-based. We used the testing dataset to evaluate the new method against the reference BP levels as well as to compare its accuracy to the commercial device. The Table illustrates the resulting BP errors. The model-based method showed, on average, 28% lower precision errors than the commercial device (statistically significant via Pitman-Morgan test with Bonferroni correction for multiple comparisons) and 41% less absolute BP errors exceeding 10 mmHg. In conclusion, the model-based method may afford more accurate automatic cuff BP measurement in patients with stiff arteries.
Abstract 19760: Longitudinal Changes in Cardiac Structure and Function After Creation of Dialysis Access in People With End Stage Kidney Disease: A 15 Year Experience
Authors: Reddy Yogesh N , Dean Patrick G , Nath Karl A , Karon Barry L , Borlaug Barry A
Published: March 2022

Introduction:
Arteriovenous fistulas(AVF) have been associated with high output heart failure but little is known about their effect on patients initiating hemodialysis. We sought to describe echocardiographic changes and identify those with incident heart failure after AVF creation.

Methods:
This was a retrospective analysis of all patients undergoing AVF creation over a 15 year period from 2000-2014 at the Mayo Clinic in Rochester, MN. Patients undergoing echocardiogram <3 months (median 40 days) before AVF creation and >6 months (median 2.5 years) following surgery were included. Patients with independent modifiers of LV structural changes (such as revascularization or myocardial infarction) were excluded by chart review. Clinical heart failure was defined by Framingham criteria.

Results:
From 2000-2014, 2236 patients underwent creation of AVFs and 137 patients met inclusion criteria. There was a longitudinal decrease in systolic function as evident by a drop in ejection fraction(-2%, p=0.047) with decrease in s’ tissue Doppler velocity(-0.6 cm/s, p=0.055) and increase in HR(+5 beats/min, p=0.003). There was also an increase in the prevalence of RV dilation(20 to 40%, p=0.002) and RV dysfunction(12 to 29%, p=0.002). With initiation of dialysis and decrease in weight (-7.3kg) and estimated plasma volume (-303ml) (both p<0.0001), there was a decrease in LV end diastolic dimension (-2mm, p=0.006). Despite better volume control, left atrial volume index increased (+5ml/m2, p=0.004). On multivariate Cox regression, worsening RV dilation [HR 1.8 (1.06-3.09),p=0.03] was independently associated with mortality. Incident heart failure developed in 43%(28/65) with no pre-existing HF, of whom 75% had HFPEF and 25% HFrEF. The development of new systolic HF (but not HFPEF) was associated with increased age and sex adjusted mortality [HR 3.0(1.0-7.9), p=0.045].

Conclusions:
AVF creation is associated with worsening biventricular function and left atrial and RV dilatation, despite reduction in LV size. These changes are coupled with high incidence of new, unexplained heart failure. Further research is needed to identify the hemodynamic mechanisms underlying heart failure development in patients with ESRD requiring dialysis access.
Abstract 19774: Weight Confirmed as a Risk Factor for Atrial Fibrillation in 39,023 Subjects
Authors: White Anthony J , Mottram Philip
Published: March 2022

Introduction:
Several risk factors for atrial fibrillation (AF) are long established including age, hypertension and left atrial volume (LAV). A more recently appreciated risk factor for AF is obesity.

Hypothesis:
We hypothesize that increased weight associates independently with atrial fibrillation.

Methods:
The database of all trans-thoracic echocardiograms (TTE) performed in a single cardiology department was interrogated for the five year period January 1, 2010 - December 31, 2014. Cardiac rhythm, age, sex, LAV, height, weight, systolic and diastolic BP data were extracted. Duplicate studies were removed. Data were analysed according to cardiac rhythm (AF vs sinus rhythm (SR)) by univariate comparisons (t tests) and multivariate linear regression.

Results:
39,023 studies were analysed [age 61±17 years, 52.8% male]. In 3,993 studies (10.2%) the cardiac rhythm was AF. The group with AF were older (74±11 vs 59±17 yrs, p<10
-20
), heavier (81.6±20.7 vs 78.6±20.0 kg, p<10
-19
), more likely male (58.9 vs 52.1%, p<10
-15
) and had larger LA volumes (71±33 vs 40±14 mL/m2, p<10
-20
) than those in SR. Height (166±11cm) was not different (p=0.69). A multivariate linear regression model was constructed incorporating age, LAV, weight, sex, diastolic and systolic BP (R
2
=0.28, p<10
-20
). In this model, weight was confirmed as an independent factor associated with AF (co-efficient 0.09, p<10
-20
).

Conclusions:
Patients with AF were 3.0 kg heavier than those in SR. Weight remained independently associated with AF in the multivariate model. These retrospective observational data lend support to recent compelling data from a prospective randomised clinical trial showing that weight loss improved control of AF.
Abstract 19779: Nod2 Knock Down Improves Left Ventricular Function and Attenuates Pathophysiological Key Mechanisms in Experimental Coxsackievirus B3-induced Myocarditis
Authors: Tschöpe Carsten , Müller Irene , Xia Yu , Zietsch Christin , Savvatis Kostas , Lassner Dirk , Kühl Uwe , Schultheiss Heinz-Peter , Pieske Burkert , Van Linthout Sophie
Published: March 2022

Introduction:
Nucleotide binding oligomerization domain 2 (NOD2) is a cytoplasmatic pattern recognition receptor belonging to the NOD-like receptor family, which is part of the innate immune system.

Hypothesis:
Since NOD2 recognises ssRNA and Coxsackievirus B3 (CVB3) is a ssRNA virus, we hypothesised that NOD2 regulates cardiac inflammatory signaling in CVB3-induced myocarditis.

Methods:
Gene expression was analyzed on endomyocardial biopsies (EMBs) taken from ejection fraction- and age-matched CVB3+ (n=10) and CVB3- control (n=7) patients and on EMBs from CVB3+patients who spontaneously eliminated CVB3 (n=6). NOD2 -/- mice and wild-type (wt) C57BL/6 mice were i.p. infected with 5 x 105 p.f.u. of CVB3. Seven days after infection, mice were hemodynamically characterized, and left ventricles (LV) were isolated.

Results:
NOD2 mRNA expression was 3.7-fold (p<0.05) increased in CVB3+ vs CVB3- control patients. Interestingly, NOD2 and Nrlp3 mRNA expression significantly dropped in EMBs of CVB3+ patients who spontaneously eliminated CVB3. In addition, LV NOD2 mRNA expession was increased in CVB3 vs wt mice. NOD2-/- CVB3 mice showed an improved LV function compared to CVB3 wt mice. In parallel, infiltration of CD4-, CD8-, CD11b- and CD68-positive cells was less pronounced in CVB3-infected NOD2-/- mice compared to CVB3 wt mice. Concomitantly, LV mRNA levels for TNF-alpha, IL-1ß, IFN-gamma, IFN-ß, TLR4, and MyD88 were 3.9-fold, 2.9-fold, 5.3-fold, 8.0-fold, 1.4-fold and 2.0-fold reduced in CVB3 NOD2-/- vs CVB3 wt mice, respectively (p<0.05). LV viral copy number was lower in CVB3 NOD2-/- vs CVB3 wt mice. CVB3-infected NOD2-/- mice exhibited less pronounced cardiac fibrosis, as indicated by lower collagen I and III mRNA expression and a 2.7-fold (p<0.0005) lower collagen I/III protein ratio. NOD2 knockdown in HL-1 cardiomyocytes was associated with a decreased inflammatory response, a 1.4-fold (p<0.05) lower CVB3 copy number, and a 3.4-fold (p<0.005) reduced TLR4 protein expression and underlying signaling.

Conclusions:
NOD2 knock down improves LV function and attenuates pathophysiological key mechanisms in acute CVB3-induced myocarditis mice. Modulation of NOD2 might represent a promising therapeutic strategy to treat viral myocarditis.
Abstract 19797: Enhanced Engraftment of Mesenchymal Stem Cells With Pro-survival Factors Improves Outcome in the Infarcted Heart
Authors: Sanchez Pablo G , Eghtesad Saman , Liu Xiaoyan , Chen Ling , Pittenger Mark F , Griffith Bartley P
Published: March 2022

Mesenchymal stem cells are under study as exemplary adult progenitor cells for repair of heart tissue injury. Many clinical studies utilizing MSCs are underway, however the ideal approach to prepare these cells in vitro, and deliver them to injury sites in vivo with maximal effectiveness is still under study. In this report, MSCs from rat bone marrow were used to examine the 1) effect of anti-apoptotic factors on the cells’ viability when challenged in vitro and 2) effect on in vivo cardiac infarct physiologic parameters.

Methods:
Lewis rats underwent myocardial ischemia and reperfusion by temporary ligation (45 min) of the left anterior descending coronary. The periinfarct area then received five myocardial injections with either untreated or anti-apoptotic factor treated MSCs. Animals underwent transthoracic echocardiography over 8 weeks.

Results:
The treated MSCs had reduced in vitro apoptosis (Figure A). The MSCs treated with anti-apoptotic factors were tested in vivo to examine if the survival of MSCs was enhanced and could improve infarct physiologic parameters. The anti-apoptotic factor treated MSCs improved the injured hearts more than untreated MSCs by echocardiographic measurements: improved ejection fraction (58.4 ± 6.5 vs. 46.6 ± 8.6 respectively, p =0.01) and greater fractional shortening (32.2 ± 4.6 vs. 24.3 ± 5.3 respectively, p =0.009). Both were better than medium alone infarct controls (Figure B). The treated MSCs were detected in the hearts in greater abundance and at later interval than the untreated MSCs.

Conclusions:
MSCs that were treated to resist apoptosis survived longer in vitro and in vivo, and improved heart function more than untreated MSCs. Injury recovery improved to a far greater extent than differentiation of the limited number of surviving cells could provide; this is consistent with the MSCs providing growth factors and cytokines to reduce inflammation and aid recovery of the endogenous cells in the region of injury.
Abstract 19809: Interferon Regulatory Factor 2 Binding Protein 2 Inhibits Macrophage Inflammation and Reduces Susceptibility to Atherosclerosis in Mice and Humans
Authors: Vilmundarson Ragnar O , Chen Hsiao-Huei , Keyhanian Kianoosh , Zhou Xun , Nikpay Majid , Cruz Shelly A , Pandey Nihar R , Almontashiri Naif A , Yap Nida L , Ho Tiffany , Stewart Chloe A , Huang Hua , Hari Aswin , Geoffrion Michele , McPherson Ruth , Rayner Katey J , Stewart Alexandre F
Published: March 2022

Introduction:
Genetic variants near the gene encoding the transcription cofactor Interferon Regulatory Factor 2 Binding Protein 2 (IRF2BP2) have been tied to ischemic heart disease progression and elevated serum cholesterol. Expression of IRF2BP2 is suppressed in inflammatory macrophages, but the significance of this down-regulation was not known.

Hypothesis:
This study sought to determine the function of IRF2BP2 in macrophages and its effect on atherosclerosis in mice and humans.

Methods and Results:
We generated mice that delete IRF2BP2 in macrophages (LysMCre/IRF2BP2flox). IRF2BP2-deficient macrophages increased atherosclerosis in irradiated LDL-receptor null recipient mice and in ApoE null mice. Atherosclerosis was associated with a skewed inflammatory macrophage polarization and increased foam cell formation. Microarray analysis revealed and promoter studies confirmed that the anti-inflammatory transcription factor KLF2 is a target of IRF2BP2, indicating an important role for IRF2BP2 in macrophage polarization.

A deletion polymorphism (rs3045215) in the 3’ untranslated sequence of human IRF2BP2 mRNA was examined for its effect on protein expression and on the susceptibility to coronary artery disease (CAD) risk in a cohort of 1,066 angiographic cases and 1,011 controls. Homozygous carriers of this deletion had lower IRF2BP2 (and its target KLF2) protein levels in peripheral blood mononuclear cells and a higher risk of CAD (recessive model, odds ratio (95%CI) = 1.560 (1.179-2.065), p=1.73E-03). The effect of this deletion to suppress protein expression was confirmed with luciferase reporter studies. Haplotype phasing identified two surrogate SNPs in modest LD (rs1887917, r2= 0.755 and rs632180, r2=0.614) that also associated with CAD in a recessive model. These SNPs are being tested for association with CAD in a large international consortium.

Conclusion:
Ablation of IRF2BP2 in macrophages worsens atherosclerosis in mice and a deletion variant that lowers IRF2BP2 expression predisposes to CAD in humans.
Abstract 19816: Recipient Body Mass Index and Role of Continuous Flow Mechanical Circulatory Assist Device in Patients Undergoing Heart Transplantation
Authors: Zalawadiya Sandip , Egolum Ugochukwu , Ooi Henry
Published: March 2022

Introduction:
Extremes of body mass indices (BMI) at the time of heart transplantation (HT) have been associated with adverse post-transplant survival. Data is limited in evaluating the survival impact of continuous flow left mechanical circulatory support (CF-LMCS) devices across categories of BMI.

Method:
We performed post-hoc analysis of 17,480 patients (age: 53±12 years, 74.5% males, 4.1 years of median follow-up) undergoing HT from the United Network of Organ Sharing (UNOS) registry database. Patients were divided into following BMI categories: underweight (BMI <18.5 kg/m2), normal (BMI 18.5 to 24.9 kg/m2), overweight (BMI 25 to 29.9 kg/m2), mildly obese (BMI 30 to 34.9 kg/m2) and morbidly obese (BMI ≥35 kg/m2); Post-transplant survival was assessed for patients with and without CF-LMCS devices across these categories of BMI using Cox-proportional hazard analysis.

Results:
See Figure 1 and 2

Conclusion:
At extremes of BMI, CF-LMCS devices had statistically non-significant association with post-HT survival. For those with BMI between 18.5 to 35 kg/m2, CF-LMCS devices offered survival advantage, suggesting that optimizing recipients' BMI within this range prior to undergoing HT may help improving their post-transplant survival.
Abstract 19833: A New Therapeutic Strategy for Refractory Cardiac Arrest Including Prehospital Ecmo: A Comparison Study
Authors: Lamhaut Lionel , Jouffroy Romain , idialisoa Rado , Ellinger Alexandre , Orsini Jean-Pierre , Hutin Alice , Jaffry Murielle , Dagron Christelle , Loosli Florian , Jouan Jerome , An Kim , Spaulding Christian , Carli Pierre
Published: March 2022

Introduction:
ECMO is a treatment of refractory cardiac arrest (RCA). The survival rate depends directly on the low flow (LF) period. To reduce LF we have implemented a new RCA management strategy. This work aims to evaluate the impact of this strategy on survival.

Methods:
This is an observational retrospective single-center study. The ECMO team is composed of a doctor, a nurse and a paramedic.The ethical committee validated the study.

During period 1 (11 / 2011-12 / 2014), the strategy associated an ECMO team alert after 10 min of ALS, followed by the implementation of ECMO either in-hospital or out of hospital depending on the ECMO team availability.

During period 2 (01-06 / 2015), the strategy associated an ECMO Team alert at the departure of the BLS Ambulance, with a dedicated ECMO team 24/24 H, and a systematic assessment for ECMO implementation either in hospital or out of hospital according to logistical constraints. A specific training was given to dispatch centers, and all ALS units.

Qualitative variables were compared using the χ2 and Fisher exact tests, whereas quantitative variables were compared by Wilcoxon tests.

Results:
The results are in Table 1. The characteristics are similar. The significant results when comparing periods 1 and 2 include an increased survival rate, a decreased LF.

Conclusions:
The survival rate of RCA treated with ECMO depends on the LF. Unfortunately even by performing a single scoop and run strategy, an important proportion of patients can not be rapidly put on ECMO.

We have developped a LF reduction strategy involving the implementation of ECMO either in hospital or in the out of hospital setting.

The optimization of this strategy by an earlier alert, a dedicated ECMO team and training has a major significant impact on survival. This increase of survival is probably correlated to the decrease of the LF, especially in the prehospital group.

These results need to be confirmed by a RCT comparing in hospital and out of hospital ECMO implementation.
Abstract 19840: Transcatheter Left Gastric Artery Therapy for Treating Obesity
Authors: Kipshidze Nicholas , Sievert Hosrt , Bertog Stefan , Archvadze Akaki , Leon Martin B
Published: March 2022

Introduction:
Obesity is associated with adverse cardiovascular and metabolic conditions. Dietary, medical or surgical weight loss strategies are frequently unsuccessful and/or accompanied by risks. Ghrelin, produced in the gastric fundus, stimulates food intake. Catheter-directed left Gastric Artery Embolization (GAE) causes a reduction in plasma ghrelin levels and weight loss in an animal model. The effect of GAE on ghrelin levels and weight in humans is unknown.

Aim:
Purpose of this study was an initial assessment of safety and efficacy of GAE in humans.

Methods:
Five obese patients underwent left GAE with BeadBlock Embolic Bead 300-500μm microspheres (Biocompatibles UK Limited, UK). Esophagogastroscopy was performed in all patients before and after GAE and at 1-week follow-up to assess for gastritis or ulcers after the procedure. Weight and fasting plasma ghrelin levels were obtained at baseline and 1-, 3-, 6- and 12-month follow-up.

Results:
The procedure was successful in all patients with no periprocedural complications. Three of 5 patients complained about mild, transient postprocedural epigastric pain. However, gastroscopy did not reveal any abnormalities. Significant progressive weight loss accompanied by reductions in plasma ghrelin levels was observed in all patients at all follow-up: mean initial weight (128.12±24.4kg) decreased to 106±21kg (p<0.001) at 20-24-month follow-up and plasma ghrelin levels (initially 473±189) decreased by 29%, 36%, 19% and 21% at 1-, 3-, 6- and 12-month follow-up (p<0.05).

Conclusions:
Percutaneous left gastric artery embolization with embolic beads as described in our study appears safe. It leads to a reduction in plasma ghrelin levels and is accompanied by a significant weight loss at intermediate term follow-up. Further studies with larger patient numbers and perhaps use of dedicated device are needed to examine the utility of this procedure and to determine the best procedural technique that allows adequate mucosal injury and ghrelin reduction while minimizing the risk of ulcer formation.
Abstract 19905: Comparative and Synergistic Effects of an Inhibitor of Integrin Outside-in Signaling With Clopidogrel and Aspirin in Inhibiting Arterial Thrombosis, and Their Different Effects on Hemostasis
Authors: Shen Xiang , Stojanovic-Terpo Aleksandra , Shen Bo , Du Xiaoping
Published: March 2022

Due to shared mechanisms of thrombosis and hemostasis, all current anti-thrombotic drugs in clinical use, including anti-coagulant and anti-platelet drugs, are associated with increased bleeding risks, which can be life-threatening. Thus, there is a need for developing new anti-thrombotics that minimally cause excessive bleeding. We have recently shown that integrin outside-in signaling, which plays an important role in occlusive thrombosis but is not required for primary platelet thrombus formation, is mediated via the interaction between integrin [[Unsupported Character - Symbol Font ]]3 subunit and heterotrimeric G protein, G[[Unsupported Character - Symbol Font ]]13. We have developed a novel inhibitor of integrin-G[[Unsupported Character - Symbol Font ]]13 interaction, mP6, which inhibits thrombosis without causing excessive bleeding in mouse models. In this study, we have directly compared effects of an improved formulation of mP6, M2mP6, with current anti-platelet drugs clopidogrel and aspirin on arterial thrombosis and hemostasis. We demonstrate that retroorbital injection of M2mP6 exerted potent anti-thrombotic effect within 5 min compared reported effects of clopidogrel of more than 1 hour. One time injection of M2mP6 (15 min, 5 μmol/kg, retro-orbital) is significantly superior to one-time ingestion of clopidogrel (2 hours, 2 mg/kg, oral) and superior to high concentrations of aspirin in inhibiting occlusive thrombosis using FeCl3-induced mouse carotid artery thrombosis model. Importantly, both clopidogrel and aspirin caused significantly prolonged tail bleeding time. In contrast, M2mP6 injection is not statistically different from control mice in tail bleeding time analysis. Furthermore, M2mP6, when used together with clopidogrel or clopidogrel and aspirin, showed synergistic effect in inhibiting occlusive thrombosis. These data demonstrates M2mP6 can potentially be a fast-acting and potent anti-thrombotic drug that does not cause adverse effect of bleeding.
Abstract 19920: Long-term Change in Cardiorespiratory Fitness and All-cause Mortality: A Follow-up Study
Authors: Laukkanen Jari A , Zaccardi Francesco , Khan Hassan , Kurl Sudhir , Rauramaa Rainer
Published: March 2022

Background:
The few studies that have assessed the association between changes in cardiorespiratory fitness and all-cause mortality have relied on exercise scores and other indirect measures of cardiorespiratory fitness (CRF). The aim of the study was to investigate whether long-term changes CRF, as assessed by the gold-standard method of respiratory gas exchange during exercise, are associated with all-cause mortality.

Methods:
Prospective cohort study (Kuopio Ischaemic Heart Disease Risk Factor Study), with a baseline examination between 1984 and 1989 (V1), a re-examination at 11 years (V2), and up to 15 years of follow-up from V2. VO
2
max was measured at both visits using respiratory gas exchange during maximal exercise test. The difference (ΔVO
2
max) was estimated as VO
2
max (V2) - VO
2
max(V1). This study was based on a population-based sample of men 42 to 60 years of age without no missing data on baseline and 11-year exercise test were included (N=579).

Results:
The mean ΔVO
2
max was -5.2 ml/min*kg. During a median follow-up of 13.3 (interquartile range: 12.5-14.0) years from V2, 123 (21.2%) all-cause deaths were recorded. In a multivariate analysis adjusted for baseline age, VO
2
max, systolic blood pressure, smoking status, low- and high-density lipoprotein cholesterol and triglycerides, C-reactive protein, body mass index, alcohol consumption, physical activity, socioeconomic status, and history of type 2 diabetes mellitus and ischaemic heart disease, 1 ml/min*kg higher ΔVO
2
max was associated with a 9% relative risk reduction of all-cause mortality (HR 0.91; 95% CI: 0.87 to 0.95) (Figure).

Conclusions:
In this population, long-term CRF reduction was associated with an increased risk of mortality, suggesting the importance of maintaining good CRF over the decades.
Abstract 19961: Protein-based Risk Score Increases Prior to Cardiovascular Events and Death in Individuals With Apparently Stable Coronary Heart Disease
Authors: Williams Stephen A , Sterling David , Kato Shintaro , Ostroff Rachel , Heidecker Bettina , Whooley Mary , Ganz Peter
Published: March 2022

Starting with 1130 plasma proteins, we previously derived and then externally validated a 9 protein model (CVD9 [angiopoietin 2, complement C7, α-2 antiplasmin, matrix metalloproteinase 12, α-1 antichymotrypsin complex, growth differentiation factors 11/8, chemokine (C-C motif) ligand 18, angiopoietin related protein 4 and troponin I]) to predict 4-year probability of death, myocardial infarction, stroke and heart failure using SOMAscan proteomic technology in subjects with stable coronary heart disease (CHD). In the current study, we tested whether this proteomic risk score increases within individuals as they approach an event. We applied CVD9 to paired plasma samples from 513 subjects in the Heart and Soul study who were still event free when a second blood sample was taken 4.8 years after the first. There were 139 subjects who had events a median of 2.9 years after their second sample, compared to 374 subjects who did not have events after their second sample (with a median of 4.3 years of further follow-up). In the events group, CVD9-predicted 4-year event probabilities were higher at baseline (median 24 % vs. 15%, [p<0.001]), and the within-subject increase over 4.8 years was greater as they came closer to their adverse event: +9% vs. +3% [p<0.001] when compared to the no-events group. In contrast, no interval change in the Framingham secondary event prediction score, traditional cardiovascular risk factors, common biomarkers or clinical parameters discriminated between groups in this way. The finding of a protein biomarker panel that is both prognostic at baseline and sensitive to impending events in patients with apparently stable CHD represents a promising advance in personalized risk monitoring.
Abstract 19972: Use of Whole Exome Sequencing for the Identification of Ito Based Arrhythmia Mechanism and Therapy
Authors: Adelman Sara H , Sturm Amy C , Kline Crystal F , Glynn Patric , Johnson Benjamin L , Curran Jerry , Kilic Ahmet , Higgins Robert S , Binkley Philip F , Janssen Paul M , Weiss Raul , Raman Subha V , Fowler Steven J , Priori Silvia G , Hund Thomas J , Carnes Cynthia A , Mohler Peter J
Published: March 2022

Background:
Identified genetic variants are insufficient to explain all cases of inherited arrhythmia. We tested whether the integration of whole exome sequencing with well-established clinical, translational, and basic science platforms could provide rapid and novel insight into human arrhythmia pathophysiology and disease treatment.

Methods and Results:
We report a proband with recurrent ventricular fibrillation, resistant to standard therapeutic interventions. Using whole-exome sequencing, we identified a variant in a previously unidentified exon of the dipeptidyl aminopeptidase-like protein-6 (DPP6) gene. This variant is the first identified coding mutation in DPP6 and augments cardiac repolarizing current (Ito) causing pathological changes in Ito and action potential morphology. We designed a therapeutic regimen incorporating dalfampridine to target Ito. Dalfampridine, approved for multiple sclerosis, normalized the ECG and reduced arrhythmia burden in the proband by
>
90-fold. This was combined with cilostazol to accelerate the heart rate to minimize the reverse-rate dependence of augmented Ito.

Conclusions:
We describe a novel arrhythmia mechanism and therapeutic approach to ameliorate the disease. Specifically, we identify the first coding variant of DPP6 in human ventricular fibrillation. These findings illustrate the power of genetic approaches for the elucidation and treatment of disease when carefully integrated with clinical and basic/translational research teams.
Abstract 19992: Delta PKC (dPKC) Binding to the “d” Subunit of F1Fo ATP Synthase (dF1Fo) Impairs Mitochondrial Energetics and Exacerbates Ischemia / Reperfusion Injury in Rats
Authors: Walker Matthew , Caldwell Robert W , Yoon Yisang , Johnson John A
Published: March 2022

We have previously demonstrated delta PKC (dPKC) involvement in cardiac myocyte energy deprivation via its interaction with dF1Fo and have developed a peptide inhibitor [NH2-YGRKKRRQRRRMLATRALSLIGKRAISTSVC-COOH] of this interaction, which targets to the mitochondrial matrix / inner membrane. In the present study, a 10 min ligation of the left anterior descending coronary artery (LAD) increased dPKC-dF1Fo co-immunoprecipitation (co-IP) by 5-fold and elevated dPKC-phosphoserine 643 immunoreactivity (a dPKC autophosphorylation site 56 +/- 17% (n=7, p<0.01) in mitochondria isolated from the left ventricular (LV) region at risk for ischemic injury (RAR). Intravenous (I.V.) injection of the dPKC-dF1Fo inhibitor (5 ug/kg) 20 min beforehand attenuated the co-IP by 71 +/- 13% (p<0.001, n=8). Blockage of the IP correlated with transient increases in cytochrome oxidase subunit IV (1.6-fold (p<0.05, n=8) and beta-tubulin (1.4-fold, (p<0.001, n=8), without changes in autophagy marker proteins (LC3II and p62) or mitochondria release of cytochrome c. The dPKC-dF1Fo inhibitor given I.V. prior to 30 min of ischemia by coronary ligation, and 3 hr of reperfusion, reduced 2,3,5-triphenyltetrazolium chloride-monitored infarct size by 29 +/- 7 % (n=6, p<0.001). This protection was correlated with a 1.7 +/- 0.2-fold (n=6, p<0.02) enhancement of ATP levels, a 2-fold reduction in tissue t-carbonyls / oxidative stress markers and a 61 +/- 12% (p<0.001, n=8)) reduction in Ca++-induced mitochondrial swelling. The inhibitor peptide also improved ADP (state 3) (1.5 +/- 0.2-fold (p<0.05, n=6) and maximal (FCCP)-stimulated (1.6 +/- 0.1-fold (p<0.03, n=6)) respiration and JC-1 monitored mitochondrial membrane potential (1.6 +/- 0.1-fold (n=6, p<0.03) following IR injury. This mitochondrially-targeted peptide therefore, protects against ATP loss, oxidative stress, mitochondrial swelling and infarction in vivo, which correlates with improved mitochondrial energetics. We propose it has potential as a first-in-class therapeutic for the treatment of cardiac IR injury.
Abstract 20031: Transcatheter Aortic Valve Replacement Using Transfemoral vs Transapical Approach: A comprehensive Meta-analysis Comparing 30-day & 1-year Cerebrovascular Event Rates
Authors: Sanam Kumar , Aggarwal Himanshu , Arora Pankaj , Gaba Saurabh , Bhatia Vikas , Bajaj Navkaranbir S
Published: March 2022

Background:
Transcatheter Aortic valve replacement (TAVR) has emerged as new technique for the management of patient with severe Aortic Stenosis (AS). Stroke is a potential complication associated with the procedure, when performed via both transfemoral (TF) and transapical approach (TA). Due to limited data, we performed a comprehensive meta-analysis comparing 30-day and 1-year stroke rates with TAVR performed using TF vs TA approach.

Methods:
We searched SCOPUS since inception to July 2014 using pre-defined criteria. The cerebrovascular event rates and type were estimated at different time points using standard random effects model.

Results:
5 studies, with total 1956 valves placed, reported 30-day stroke rates with TA approach, and 9 studies, with 1146 valves, reported stroke rates with TF approach. No significant difference (p=0.313) was noted with TA vs TF approach with stroke rates 1.74 (0.61-2.87), 1.52 (0.71-2.33) respectively

(Figure 1, Panel A).

Similarly, 4 studies, with total 1657 valves, reported 1-year stroke rates with TA approach, and 8 studies, with 1034 valves, reported stroke using TF approach. Again, no significant difference (p=0.161) was noted with TA vs TF approach with adjusted stroke rates 3.78 (1.72-5.85), 3.11 (1.49-4.74) respectively

(Figure 1, Panel B).

Conclusion:
We did not observe any difference in stroke rates when TAVR is performed using transapical versus transfemoral approach.
Abstract 20097: Burden of Arrhythmias in Patients Hospitalized With Cardiac Amyloidosis
Authors: Rochlani Yogita M , Nishi Shah N , Hakeem Abdul , Bhatti Sabha
Published: March 2022

Introduction:
Cardiac Amyloidosis (CA) predisposes patients to atrial and ventricular arrhythmias. Data on distribution of arrhythmias in this patient population is scarce. We sought to study the prevalence of various types of arrhythmias in this vulnerable patient population.

Methods:
Patients hospitalized with a diagnosis of CA were identified using appropriate ICD 9 codes from the Nationwide Inpatient Sample for the period between 2007-2011. Cardiac arrhythmias listed in the discharge diagnosis were recorded based on ICD 9 codes. Statistical analysis was done using SAS v9.3 (Cary Institute Inc., Cary, NC).

Results:
A total of 13,602 patients hospitalized for CA between 2007-2011 were identified of which 52.6% (n=7157) had an arrhythmia listed during the hospitalization (table). The most common arrhythmia was atrial fibrillation (AF) (32.3%, n= 4390), followed by ventricular tachycardia (9.9%, n=1352), atrial flutter (6.5%, n=878) and atrioventricular blocks (3.5%, n=470). There was no gender difference in prevalence of arrhythmias. All-cause mortality during hospitalization was 10%. In hospitalized patients, ventricular tachycardia was the most common life threatening arrhythmia followed by ventricular fibrillation.

Conclusions:
CA patients have a high arrhythmia burden with a high incidence of AF and life threatening arrhythmias such as ventricular tachycardia and fibrillation. Whether this patient population will benefit from ICD implantation for primary prevention is not clearly known. Further research is required to identify specific arrhythmic risk factors and develop guidelines for primary prevention of sudden cardiac death in this patient population.
Abstract 20132: Drug-eluting Stents versus Bare Metal Stents for Non-ST-segment Elevation Myocardial Infarction (NSTE-ACS): A Meta-analysis of 44,123 Patients
Authors: Bavishi Chirag , Khan Abdur R , Trivedi Vrinda , Gongora Carlos , Ather Sameer
Published: March 2022

Introduction:
The efficacy of drug-eluting stents (DES) compared to bare-metal stents (BMS) in patients with Non-ST-segment Elevation Myocardial Infarction (NSTE-ACS) is unclear.

Methods:
Pubmed, Scopus and Clinical trials.gov databases were searched to identify all studies that compared DES with BMS in patients with NSTE-ACS. We evaluated the following efficacy and safety outcomes: all-cause mortality, cardiovascular mortality, myocardial infarction, stent thrombosis, target vessel revascularization and major advance cardiovascular events (MACE) at the longest reported follow-up times. Random-effects model was used to pool study results.

Results:
A total of 11 cohort studies with 44,123 patients were included. The mean follow-up duration was 2.3 years. Of note, all studies compared first generation DES with BMS. Patients receiving DES had significantly lower all-cause mortality (Relative risk [RR]: 0.74, 95% confidence interval [CI]: 0.64 - 0.86, p<0.001), cardiovascular mortality (RR: 0.73, 95% CI: 0.54 - 0.99, p=0.02), MACE (RR: 0.71, 95% CI: 0.54 - 0.94, p=0.02) and target vessel revascularization (RR: 0.64, 95% CI: 0.49 - 0.82, p=0.001). There was no significant difference in the incidence of myocardial infarction (RR: 0.88, 95% CI: 0.67 - 1.15, p=0.34) and stent thrombosis (RR: 0.98, 95% CI: 0.71 - 1.35, p=0.89).

Conclusions:
Compared to BMS, DES is associated with improved outcomes with non-significant differences in myocardial infarction and stent thrombosis. Further randomized controlled trials including studies with newer DES, are required to evaluate the efficacy and safety of DES in patients with NSTE-ACS.
Abstract 20169: A Novel Early Warning System to Predict Critical Events in Children With Congenital Heart Disease
Authors: Shin Andrew Y , Liu Rui , Yarlagadda Vamsi , McElhinney Doff , Almond Christopher , Ling Xuefeng
Published: March 2022

Background:
The outcome of hospitalized patients suffering clinical decline is contingent upon timely recognition. Current algorithms utilize select clinical variables for predictive modeling but have generally excluded congenital heart disease due to heterogeneity of patient and disease. The purpose of this study is to develop a model to predict decline in congenital heart disease patients.

Methods:
We analyzed all patients admitted to the Heart Center at Stanford Children’s Health between 9/1/2009 and 12/31/2012. We profiled the phenotypic changes in the EMR and measured entropy defined as the degree of fluctuation in all EMR values at 3-hour intervals. Predictive modeling was performed to identify temporal and directional relationships between entropy and the occurrence of a critical event, compared to the entropy of matched control patients. The entropy index was derived retrospectively in the first two-thirds of patients, and applied prospectively in the final third to determine predictability.

Results:
A total of 2,658 encounters occurred. A total of 71 (2.6%) critical events were observed as defined by calls for rapid response team, code blue, and ECMO. Peak entropy within the EMR was observed at mean of 15 (±5.4) hours prior to critical events (Figure). In the prospective arm, the area under the ROC curve for predicting critical events was 0.80 (95% confidence interval [CI]: 0.75-0.83). The sensitivity and specificity derived from the ROC curve was 68.4% and 74.6%, respectively. Only 2% of EMR variables were found in all cases and 14% of all critical events shared 3 or more common variables.

Conclusion:
Common EMR variables that cluster uniquely in relation to critical events among children hospitalized for cardiac disease are rare, which poses a challenge to early warning systems that are based on specific variables. Leveraging the EMR to detect increased entropy as a novel predictor of crisis event in this population merits further investigation.
Abstract 20179: Correlation Between Visceral Fat and Coronary Artery Calcium in Metabolic Syndrome Patients
Authors: Park Jae Hyoung , Nam Hyo-Jung , Lim Do-Sun
Published: March 2022

Introduction:
To assess the relationship between visceral fat (VF) and coronary artery calcium (CAC), we performed visceral fat scan and coronary CT angiography (CCTA) in metabolic syndrome (MetS) cohort.

Hypothesis:
There is correlation between VF and CAC.

Methods:
From January to September 2014, among 1000 MetS patients who were referred from 24 public health centers in Seoul, 740 patients who performed visceral fat scan (HDS-2000, Omron) were enrolled in this analysis. MetS was defined as any three of the following traits in one individual: abdominal obesity (waist circumference of men>90cm, women>85cm), high triglyceride (TG) (>150mg/dL), low high-density lipoprotein cholesterol (HDLc) (men100mg/dL). Severity of fatty liver were graded from 0 to 3 by ultrasound. Brachial ankle pulse wave velocity (PWV), carotid intima-media thickness (IMT), Left ventricular mass index (LVMI), CAC and Augmentation index (AIx) were also measured.

Results:
The cut-off value of high VF area was calculated 88cm2 by Youden index. Incidence of MetS patients who had high VF area (≥88cm2) was 36% (267/740) and the prevalence of men was higher than women (53.4% vs 18.7%, p<0.001). High VF group showed higher CAC than normal VF (11.2±43 vs 25.6±95, p=0.025). VF showed positive correlation with PWV and IMT (p=0.028 and 0.019). LVMI, CAC, abdominal subcutaneous fat, fatty liver grade, serum glucose, TG, HDLc, TG/HDLc ratio, systolic and diastolic blood pressure were also positively correlated with VF (all of the p< 0.01).

Conclusions:
High VF group showed high CAC. Moreover, VF area showed positive correlation with PWV, IMT, LVMI, CAC, TG/HDLc ratio, abdominal obesity, fatty liver grade and abdominal subcutaneous fat in MetS cohort. It may be considered that VF can predict severity of CAC, arterial stiffness, atherosclerosis, insulin resistance and fatty liver in MetS.
Abstract 9739: Predictive Values of ST-segment Elevation in Lead aVR for the Diagnosis of Left Main or 3-Vessel Disease in Patients With Non-ST-segment Elevation Acute Coronary Syndrome
Authors: Kosuge Masami , Ebina Toshiaki , Hibi Kiyoshi , Tsukahara Kengo , Iwahashi Noriaki , Maejima Nobuhiko , Akiyama Eiichi , Umemura Satoshi , Kimura Kazuo
Published: March 2022

Introduction:
In patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS), early identification of left main or 3-vessel disease (LM/3VD) is important in selecting the optimal treatment strategy.

Hypothesis:
ST-segment elevation in lead aVR (ST↑aVR) at presentation is considered a useful predictor of LM/3VD; however, time from symptom onset to presentation may influence its predictive value.

Methods:
We studied 835 patients with NSTE-ACS undergoing coronary angiography during hospitalization. We evaluated ECG findings and troponin T (TnT), estimated glomerular filtration rate (eGFR), brain natriuretic peptide (BNP), high-sensitivity C-reactive protein (hsCRP), and TIMI risk score on admission.

Results:
The prevalence of LM/3VD was 21%. Patients with LM/3VD were older (70±11 vs 66±11 yrs), had higher rates of hypertension (72% vs 64%), diabetes mellitus (51% vs 30%), Killip class ≥2 (31% vs 6%), positive-troponin T (≥0.1 ng/ml) (57% vs 29%), and ST↑aVR ≥0.5 mm (79% vs 15%), and had higher levels of BNP (367±407 vs 184±398 pg/ml), hsCRP (0.908±2.564 vs 0.371±1.425 mg/dl), and summed ST-segment depression (9±7 vs 2±3 mm), and TIMI risk score (3.7±1.2 vs 2.6±1.4) and a lower eGFR (54±27 vs 66±24 ml/min/1.73 m2), and a higher rate of in-hospital death, (re)infarction, or urgent revascularization (36% vs 9%) than did those without LM/3VD (all p<0.05). Multivariate analysis showed that ST↑aVR (OR 10.8, 95%CI 3.88-20.1, p<0.01) was the strongest predictor of LM/3VD, and followed by positive-troponin T (OR 2.20, 95%CI 1.26-4.01, p<0.01). When patients were subdivided according to the 6-h time window from symptom onset, the predictive values of ST↑aVR for the diagnosis of LM/3VD were significantly higher than those of positive-troponin T, except the sensitivity in delayed presentation (Table).

Conclusions:
In patients with NSTE-ACS, ST↑aVR on admission strongly predicted LM/3VD; however, its sensitivity decreased in delayed (>6 h) presentation.
Abstract 9763: Cardiac Beta-arrestin2 Promotes Contractility by Enhancing SERCA2a SUMOylation and Activity
Authors: Lymperopoulos Anastasios , Jafferjee Malika , McCrink Katie A , Reyes Valero Thairy , Marrero Christine , Brill Ava , Huang Xupei
Published: March 2022

Introduction:
Heart failure (HF) is the number one killer in the US and new treatments are needed. Sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA)-2a is a crucial cardiac protein regulating contractility and its downregulation is a molecular hallmark of chronic HF. Its activation underlies β1-adrenergic receptor (AR)-induced cardiac contractility. Agonist-bound β1ARs undergo functional desensitization/internalization due to the actions of βarrestin1 or -2. The two βarrestins are universal receptor adapter proteins and signal transducers thanks to protein scaffolding. Among the cellular processes they can regulate, is protein SUMO (small ubiquitin-like modifier)-ylation, generally increasing protein stability/levels. In the heart, βarrestin1 appears detrimental, whereas βarrestin2 beneficial, for structure and function post-myocardial infarction (MI). Post-MI βarrestin1 knockout mice display elevated SERCA2a activity and better contractility than post-MI wild type (WT) mice. In addition, reduced cardiac SERCA2a SUMOylation is known to underlie its downregulation in HF, decreasing cardiac contractility.

Hypothesis:
Cardiac β1AR-activated βarrestin2 promotes SERCA2a SUMOylation and activity, thereby regulating contractility.

Methods & Results:
By studying individual βarrestin knockout heart extracts, we found that βarrestin2, but not βarrestin1, interacts with SERCA2a in the mouse heart in vivo, promoting the latter`s SUMOylation and activity. This interaction is direct, as indicated by pulldown and FRET experiments. In vitro studies in the cardiomyocyte line h9c2 indicate that this interaction is both β1AR-, and β-agonist-specific, and leads to increased Ubc9-dependent SERCA2a SUMOylation, which, in turn, acutely enhances SERCA2a activity. This results in significantly enhanced cardiac function in post-MI HF mice in vivo (Ejection Fraction of WT post-MI mice overexpressing βarrestin2 in the heart vs. control post-MI mice: 46+2.8% vs. 34+2.1%, respectively, p<0.05, n=5).

Conclusions:
These results suggest that βarrestin2, presumed, like βarrestin1, to decrease cardiac function by desensitizing βARs, may actually (directly) enhance cardiac contractility, thereby opposing βarrestin1 in that regard.