bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 12644: Growth Differentiation Factor-15 (GDF-15) for Risk Stratification in Patients After an Acute Coronary Syndrome: Insights From the SOLID-TIMI 52 trial
Authors: Toda Kato Eri , Morrow David A , Cannon Christopher P , Lukas Mary Ann , Budaj Andrzej , Hamm Christian W , Jarolim Petr , Im KyungAh , Zhou Jing , Braunwald Eugene , O’Donoghue Michelle L
Published: July 2021

Background:
Growth differentiation factor (GDF)-15, a stress responsive cytokine, is associated with the risk of CV events after an acute coronary syndrome (ACS). Unlike other established cardiac biomarkers, the level of GDF-15 remains elevated in sub-acute phase after ACS and gradually decreases over time. We evaluated the prognostic utility of GDF-15 in patients after ACS accounting for established markers and risk predictors.

Methods:
GDF-15 (R&D Systems) and other established cardiac biomarkers (BNP, hsCRP and hsTnI) were measured at baseline in a randomly selected cohort of 4,968 patients enrolled within 30 days of hospitalization with ACS (median=14d) in SOLID-TIMI 52. Previously defined cutpoints were applied for GDF-15 concentration: <1200 (n=3451), 1200-1800 (n=919), and > 1800 ng/L (n=598). Analyses were adjusted for established risk predictors, days from the ACS event and other markers. MACE was defined as CV death, MI or stroke. Median follow-up was 2.5 years.

Results:
Patients with higher GDF-15 tended to be older, more likely to have diabetes, hypertension, history of revascularization, and CKD at baseline. Higher baseline levels of GDF-15 identified patients with higher rates of MACE as well as each individual element (p-trend <0.001 for all endpoints, Fig). The rate of MI was ∼2-fold higher in those with GDF-15 concentration >1800ng/L compared to patients with GDF-15 concentration <1200 ng/L. After adjustment for clinical predictors and other markers, GDF-15 was independently associated with the risk of MACE (HR 1.4, 95% CI 1.1-1.7; HR 1.8, 95% CI 1.4-2.3 for GDF-15 1200-1800, >1800, respectively). Individuals with GDF-15 >1800 ng/L had an increased risk of MI (adj HR 1.4, 95% CI 1.1-2.0) and stroke (adj HR 2.3, 95% CI 1.3-3.9).

Conclusion:
In patients after ACS, GDF-15 concentration is associated with the risk of MACE including MI and stroke independent of traditional risk factors and risk markers.
Abstract 12668: Geriatric Patients Admitted for Heart Failure are Less Likely to Have Follow-up Appointments Scheduled Prior to Discharge
Authors: Goyal Parag , Beecy Ashley N , Sterling Madeline , Ruffino John T , Mehta Sonal , Lachs Mark S , Jones Erica C , Horn Evelyn M
Published: July 2021

Introduction:
Post-discharge medical follow-up among geriatric patients admitted with heart failure (HF) is especially important given high rates of multimorbidity and polypharmacy.

Hypothesis:
Patients admitted with HF aged ≥65 years will have a high rate of follow-up appointments (FUA) scheduled upon discharge from the hospital.

Methods:
We studied patients discharged home from a medicine service with principal diagnosis of HF at an academic hospital in NYC during 2013-2014. Patients discharged to hospice were excluded. We collected demographics, hospitalization characteristics, clinical indices, and FUA data by chart review.

Results:
. 796 unique patients were hospitalized with HF, among whom 443 (56%) had an FUA scheduled prior to discharge. Patients who did not have an FUA were older, more commonly white, and less likely to have Medicaid (Table). They had higher LVEF and higher rates of HFpEF (LVEF≥50%) compared to those with an FUA. Patients with and without an FUA were similar with respect to rates of coronary artery disease (CAD), RV dysfunction, valvular disease, atrial fibrillation/flutter (AF), and ventricular tachycardia. Patients also had similar rates of non-cardiac comorbidities irrespective of having an FUA, with the exception of COPD, which was more common among those with an FUA. Despite increased rates of CAD, AF, COPD, gastrointestinal bleeding, cancer, and cerebrovascular accidents, patients aged ≥65 years were less likely to have an FUA (52% vs. 65%, p=0.001). In multivariate analysis controlling for race, insurance, COPD, and HFpEF, age ≥65 remained independently associated with not having a scheduled FUA upon hospital discharge (OR 1.45, [1.02 to 2.05], p=0.03).

Conclusions:
Despite higher burden of both cardiac and non-cardiac disease, patients aged ≥65 years admitted with HF were less likely to have a follow-up appointment upon discharge. This highlights an important disparity in care of the geriatric population that must be addressed.
Abstract 12688: Abdominal Aortic Aneurysm in Marfan Syndrome: Time for Screening Guidelines?
Authors: Hagerty Tracy , Geraghty Patrick , Braverman Alan C
Published: July 2021

Background:
Marfan syndrome (MFS) leads to aortic root aneurysm, while descending thoracic aortic aneurysm (TAA) occurs less commonly. With imaging surveillance and prophylactic surgery, lifespan in MFS has increased to near normal. Abdominal aortic aneurysm (AAA) complicating Marfan syndrome is rarely reported in the literature. There are no guidelines for routine screening for AAA in MFS. We sought to characterize AAA disease in our MFS cohort.

Methods:
The records of 11 adults from our MFS Clinic with MFS (by Ghent or revised Ghent Criteria) and AAA disease were reviewed. Clinical features, imaging, operative reports, and outcomes were analyzed.

Results:
Eleven adults (9 male) with MFS and AAA, age at AAA diagnosis 43
+
15 yrs (range 18-63 yrs), were studied. Five patients smoked cigarettes. Nine of eleven patients were being treated with beta-blockers and angiotensin receptor blockers or ACE-inhibitors at the time of AAA diagnosis. Ten underwent prior aortic root replacement at age 31
+
15 yrs (range 8-62 yrs). The AAA was diagnosed 1-21 years after aortic root repair. The AAA was suprarenal in 5 patients, juxtarenal in 2, and infrarenal in 4. The size of the AAA ranged from 3.5 to 9.7 cm at time of diagnosis. Three patients had descending TAA. One patient had a prior type B dissection, not involving the abdominal aorta. Branch vessel aneurysms present in these patients included popliteal, intercostal, hepatic, subclavian and axillary. Four patients underwent open surgical repair (AAA size from 5.5 to 9.7 cm); one underwent endovascular repair; and five are being treated medically (aortic size 4.1
+
0.6 cm). One patient died suddenly with AAA size 5.7 cm at last measurement.

Conclusions:
Adults with MFS are at risk for developing AAA. Our cohort is the largest to date characterizing AAA in MFS. The AAAs were often very large at the time of initial diagnosis. MFS patients with AAA have a relatively high frequency of branch vessel aneurysms. Imaging to evaluate for AAA is recommended early after the diagnosis of MFS in adults and periodically thereafter to improve outcomes in this population.
Abstract 12810: Beta Blockers and Mortality Benefit in Patients With Heart Failure and End Stage Renal Disease on Hemodialysis
Authors: Inampudi Chakradhari , Cotarlan Vlad
Published: July 2021

Background:
Post-hoc analysis of Randomized control trials have established safety and efficacy of Beta blockers (BB) in patients with systolic heart failure (HF) and mild to moderate Chronic kidney disease (CKD). However, the mortality benefit in patients with advanced CKD especially those approaching end stage renal disease (ESRD) is limited. The study was sought to identify mortality benefit in patients with Heart failure (HF) and ESRD who progressed to dialysis.

Methods:
Using electronic medical records, we identified 1,817 patients with end stage renal dialysis(ESRD) who progressed to dialysis over a 6 year period between 2004 and 2011. Kaplan Meyer survival curves were used to assess the association between BB use and mortality.

Results:
Of 1817 patients (mean age 61+/-15, 57% males) with ESRD who progressed to dialysis, 1329 (73.1%) were treated with BB and 488 (26.5%) were never treated with a BB. Kaplan Meyer Survival curves showed that patients who received treatment with BB had better survival than patients who were never treated with BB despite more HTN and diabetes present in the former group (mean survival time 4.9 years versus 4.4 years, p<0.001, Fig 1). Survival graphs were similar for those with an encounter diagnosis of HF (n=547, Fig 2) and those without an encounter diagnosis of HF (n=1270, graph not shown) with stronger association between BB and survival among those with HF (mean survival 3.1 versus 4.8 years, p=0.001, Fig 2).

Conclusion:
Treatment with BB is associated with improved survival in heart failure patients with ESRD who progressed to dialysis.
Abstract 12812: Leg Muscle Strength Independently Predicts Clinical Outcome In Patients With Acute Decompensated Heart Failure
Authors: Park Je-Wook , Youn Jong-Chan , Oh Jaewon , Park Sungha , Lee Sang-Hak , Choi Donghoon , Kang Seok-Min
Published: July 2021

Introduction:
Leg muscle strength (LMS) could be an index of frailty in patients with heart failure. However, its prognostic value in patients with acute decompensated heart failure (ADHF) is not well investigated.

Hypothesis:
We hypothesized that impaired LMS was independently associated with poor clinical outcome in patients with ADHF.

Methods:
We measured LMS in 110 prospectively and consecutively enrolled ADHF patients (75 male, mean age 60 ± 14 years, mean ejection fraction 29.9 ± 14.6%) at predischarge period. Primary endpoint was cardiovascular (CV) events defined as CV mortality, cardiac transplantation or rehospitalization due to HF aggravation.

Results:
The CV events occurred in 28 (25.5%) patients (5 cardiovascular deaths and 6 cardiac transplantations) during follow up period (median 246 days, 11-888 days). When the patients with ADHF were divided by LMS according to Contal and O’Quigley's method, impaired LMS was shown to be associated with poor clinical outcome (P<0.001). Multivariate Cox regression analysis revealed that LMS was found to be an independent predictor of CV events (P=0.017) when controlled for age, gender, BMI, types of heart failure, hemoglobin, NT-proBNP and beta-blocker use.

Conclusions:
LMS independently predicts clinical outcome in patients with ADHF and might be used as a surrogate marker of frailty. Further studies are needed to evaluate the prognostic role of leg muscle strengthening exercise in these patients.
Abstract 12849: Changes in N-terminal Pro Brain Natriuretic Peptide Levels Predicts Mortality and Heart Failure Hospitalization in Patients With Heart Failure and Preserved Ejection Fraction
Authors: Savarese Gianluigi , Hage Camilla , Dahlström Ulf , Perrone-Filardi Pasquale , Lund Lars H
Published: July 2021

Introduction:
Changes in N-terminal pro brain natriuretic peptide (NT-proBNP) have been demonstrated to correlate with outcomes in patients with heart failure (HF) and reduced ejection fraction (EF). However the prognostic value of a change in NT-proBNP in patients with heart failure and preserved ejection fraction (HFPEF) is unknown.

Hypothesis:
To assess the impact of changes in NT-proBNP on all-cause mortality, HF hospitalization and their composite in an unselected population of patients with HFPEF.

Methods:
643 outpatients (age 72+12 years; 41% females) with HFPEF (ejection fraction ≥40%) enrolled in the Swedish Heart Failure Registry between 2005 and 2012 and reporting NT-proBNP levels assessment at initial registration and at follow-up were prospectively studied. Patients were divided into 2 groups according the median value of NT-proBNP absolute change that was 0 pg/ml. Median follow-up from first measurement was 2.25 years (IQR: 1.43 to 3.81). Adjusted Cox’s regression models were performed using total mortality, HF hospitalization (with censoring at death) and their composite as outcomes.

Results:
After adjustments for 19 baseline variables including baseline NT-proBNP, as compared with an increase in NT-proBNP levels at 6 months (NT-proBNP change>0 pg/ml), a reduction in NT-proBNP levels (NT-proBNP change<0 pg/ml) was associated with a 45.2% reduction in risk of all-cause death (HR: 0.548; 95% CI: 0.378 to 0.796; p:0.002), a 50.1% reduction in risk of HF hospitalization (HR: 0.49; 95% CI: 0.362 to 0.689; p<0.001) and a 42.6% reduction in risk of the composite outcome (HR: 0.574; 95% CI: 0.435 to 0.758; p<0.001)(Figure).

Conclusions:
Reductions in NT-proBNP levels over time are independently associated with an improved prognosis in HFPEF patients. Changes in NT-proBNP could represent a surrogate outcome in phase 2 HFPEF trials.
Abstract 12850: Complex Lesion Characteristics Would be the Potential Risk Factors for Ventricular Fibrillation With Acute Coronary Syndrome
Authors: Sugizaki Youichirou , Takemoto Makoto , Toki Hiromi , Taniguchi Yu , Igarashi Nobuaki , Murata Takeomi , Doi Tomohumi
Published: July 2021

Background:
In the setting of acute coronary syndrome (ACS), ventricular fibrillation (VF) was serious and fatal complication. However, even though ischemia was well known as the risk for occurrence of VF, what influential factors of ACS patients related to VF were still unclear. We performed extracorporeal cardiopulmonary resuscitation for VF with ACS patients taken to our institute and performed coronary angiography to make definite diagnosis. Accordingly, We sought to the risk factors for VF with ACS.

Methods:
Consecutive 246 ACS patients hospitalized and underwent emergent coronary revascularization from September 2010 to September 2014 were enrolled. In these, patients with VF were categorized into VF group, and patients without VF were into non-VF group. We reviewed patients’ characteristics, including medications, past histories and laboratory findings, and CAG findings (lesion characteristics with ACC/AHA classification, number of disease vessels, existence of chronic total occlusion (CTO) and left-main coronary artery (LMCA) lesion) retrospectively.

Results:
Fifty-seven patients developed ACS with VF (VF group), and 189 patients were without VF (non-VF group). Comparing between the groups, the morbidity of previous angina pectoris or coronary artery bypass grafting were significantly higher in VF groups (32.1%-16.0%, p=0.01, 14.3%-1.1%, p<0.001, respectively). The prevalence of Complex lesion characteristics, such as multi vessel disease, CTO and LMCA lesion, was also higher in VF group (71.9%-42.8%, 43.9%-13.9%, 15.8%-6.3%, all p < 0.025, retrospectively). Moreover, multiple logistic regression analysis revealed multi vessel disease and existence of CTO lesion were independent factors for VF.

Conclusion:
VF group had more complex characteristics of coronary artery disease. Complex lesion characteristics, such as multi vessel disease, CTO and LMCA lesion, would be potential risk factors of VF with ACS patients.
Abstract 12873: Blood Transfusion and the Risk of Contrast-Induced Nephropathy Among Acute Coronary Syndrome Patients Undergoing Percutaneous Coronary Intervention
Authors: Karrowni Wassef , Vora Amit N , Dai Dadi , Wojdyla Daniel , Dakik Habib , Rao Sunil
Published: July 2021

Introduction:
Emerging scientific and clinical evidence suggests that blood transfusion might be risk factor for acute kidney injury.

Hypothesis:
Blood transfusion is independently associated with contrast-induced nephropathy (CIN) in acute coronary syndrome (ACS) patients undergoing PCI.

Methods:
Retrospective cohort study from the NCDR CathPCI Registry (2009-2014) (n=1,756,864). Primary outcome was CIN defined as rise in serum creatinine peak post-procedure ≥ 0.5 mg/dl or ≥ 25% above baseline.

Results:
CIN developed in 9.0% of the cohort; these patients were older (66.0 vs. 64.0 years; P<0.01), more often female (43.2% vs. 31.9%; P<0.01), and had more baseline comorbidities including DM (46.1%), hypertension (85.1%), and lower baseline GFR. Blood transfusion was utilized in 38,626 (2.2%) of patients. The adjusted OR for the risk of CIN with transfusion in the overall sample, patients with major bleeding, and patients with no bleeding were 4.87 (4.71-5.04), 2.21 (2.12-2.31), and 4.80 (4.40 - 5.24) respectively (Table). Association of CIN with transfusion was significantly increased across all pre-procedure hemoglobin (Hgb) levels and in stepwise fashion with increasing Hgb levels and regardless of post-procedure bleeding (Hgb <=10: adjusted OR (95%CI) 2.90 (2.75-3.05); Hgb >10 to <=13: 5.26 (5.06-5.48); Hgb >13 to <=15: 6.37 (5.99-6.78); Hgb >15 g/dl: 7.03 (6.43-7.67); Ptrend <0.01).

Conclusions:
Blood transfusion is strongly associated with CIN in ACS patients undergoing PCI. Whether a restrictive blood transfusion strategy lowers the risk of contrast nephropathy should be investigated.
Abstract 12902: Association of Statin Use and Endogenous Serum Sex Hormone Levels in the Multi-ethnic Study of Atherosclerosis(MESA) Cohort
Authors: Oluleye Oludamilola , Kronmal Richard , Folsom Aaron , Ouyang Pamela , Vaidya Dhananjay , Duprez Daniel , Yarmohammadi Hirad , Dobs Adrian , Konety Suma
Published: July 2021

Background:
The new 2013 ACC/AHA cholesterol guidelines recommend statin therapy to reduce atherosclerotic cardiovascular disease. Statins inhibit cholesterol biosynthesis which may impair gonadal steroidogenesis. Higher levels of estradiol (E2) and lower levels of sex hormone binding globulin (SHBG) are associated with greater central obesity, metabolic syndrome and diabetes in both men and postmenopausal women. There is however limited information regarding the impact of statins on endogenous sex hormones in large population studies.

Methods:
We included 3163 men and 1977 women from the baseline examination of the MESA study who had measurement of serum sex hormones: total and bioavailable testosterone (T), E2, dehydroepiandrosterone (DHEA) and SHBG, and excluded those on hormone replacement therapy and non-statin lipid medications.

Results:
Of the 5140 individuals examined, statin users (n=812) were 67
+
9 years old, 57% males, 41% Whites, 29% Blacks, 11% Chinese and 19% Hispanics. After adjustment for age, gender and race, total cholesterol, HDL-c and BMI, compared to non-users of statins, statin users had significantly lower SHBG by 4.5 nmol/L (95% CI; -6.1, -2.9) and DHEAS by 0.9 nmol/L (95% CI; -1.4, -0.4). No significant gender interaction with statin was seen. No association was noted between statin use and E2, total and bioavailable T.

Conclusion:
Statin use is associated inversely with serum SHBG and DHEA levels. This is particularly interesting in light of the association of statin use and diabetes, raising the possibility of mediation by endogenous hormones.
Abstract 12905: Gene Expression and Expression Quantifying Trait Loci Analysis of Left Atrium of Patients With Post-operative Atrial Fibrillation
Authors: Sigurdsson Martin I , Heydarpour Mahyar , Saddic Louis , Chang Tzuu-Wang , Shernan Stanton K , Shekar Prem , Aranki Sary , Couper Gregory , Muehlschlegel Jochen D , Body Simon C
Published: July 2021

Introduction:
The majority of information on the genetic background of atrial fibrillation (AF) results from genomic DNA variant analysis without consideration of tissue expression.

Hypothesis:
Analysis of tissue-specific gene expression in left atrium (LA) can further understanding of the molecular mechanism of identified AF risk variants, and identify novel genes and gene variants associated with AF.

Methods:
We isolated mRNA from samples of the LA free wall taken during mitral valve surgery in 62 Caucasian individuals. Gene expression in the LA was compared between patients who did and did not have post-operative AF (poAF) using high-throughput RNA expression. Using genotypes of 1.4 million single nucleotide polymorphisms (SNP) we performed cis expression quantifying trait loci (eQTL) analysis, correlating gene expression of each gene with the genotypes of adjacent (<1Mbp) SNPs.

Results:
We identified 23 differentially expressed genes in the LA of patients with poAF, including three potassium channel genes (KCNA7, KCNH8 and KCNK17). The largest expression difference was in LOC645323, a long non-coding RNA. The expression of PITX2, ZFHX3 and KCNN3, previously shown to be associated with AF, did not differ between patients with and without poAF. We identified 12,476 cis eQTL relationships in the LA, several of those included genetic regions and genes previously associated with AF. We confirmed an eQTL relationship between rs3744029 genotype and the expression of MYOZ1. Furthermore we describe a novel eQTL relationship between rs6795970 genotype and the expression of the SCN10A gene.

Conclusions:
We have analysed the human LA expression via high-throughput RNA sequencing, and identified novel genes and gene variants likely involved in the molecular pathophysiology of AF.
Abstract 12976: Malignant Type of Electrical Storm in Patients With an Implantable Cardiac Shock Device: Results From the Nippon Storm Study
Authors: Noda Takashi , Kurita Takashi , Nitta Takashi , Frushima Hiroshi , Matsumoto Naoki , Toyoshima Takeshi , Shimizu Akihiko , Mitamura Hideo , Ohe Tohru , Aizawa Yoshifusa
Published: July 2021

Introduction:
Electrical storm (ES) referred to as multiple device therapies is an important clinical problem in patients (pts) with an implantable cardiac shock device (ICSD), such as implantable cardioverter-defibrillator or cardiac resynchronization therapy device with defibrillator. Detailed clinical aspects of ES, however, remain unclear in the Asian large population.

Methods:
We analyzed the data of the Nippon Storm Study which was a prospective observational study and consisted of 1570 pts enrolled from 48 Japanese ICSD centers designed to clarify the clinical aspects of ES. The study population included 493 (31%) pts with ischemic heart disease (IHD) and 357 (23%) pts with dilated cardiomyopathy (DCM). They had a mean LVEF of 43±19 %.

Results:
ES occurred in 96 (6.4%) pts during a median follow-up of 28 (23-33) months. Compared to pts without ES, pts with ES showed a significantly lower left ventricular ejection fraction (43% vs 38 %, respectively, p=0.005). No significant difference regarding ES incidence was observed between pts with IHD and pts with DCM (log-rank p=0.77). A sub-analysis of the ES characteristics revealed that the mortality in patients with shock therapy during the first ES episode and those with the incidence of multiple episodes of ES during the follow-up was significantly higher than those without (12/18 vs 30/78; p=0.03, 12/18 vs 26/78, p<0.01, respectively, Table).

Conclusions:
Shock therapy during the first ES episode and multiple episodes of ES were related to significantly higher mortality in pts with ICSD. There can be a malignant entity of ES.
Abstract 13021: Regional Electromechanical Heterogeneity in the Rabbit Wild-Type and Long-QT-Syndrome Heart
Authors: Dressler Franz F , Bodi Ilona , Menza Marius , Perez-Feliz Stephanie , Zehender Manfred , Bode Christoph , Behrends Jan C , Seemann Gunnar , Odening Katja E
Published: July 2021

Introduction:
Long-QT-syndrome type 2 (LQT2) has been linked to heterogeneities on a whole-heart scale. Here, we systematically investigated regional electromechanical function in wild-type (WT) and transgenic LQT2 rabbits.

Methods:
Rabbits (n=7 WT, 6 LQT2) were examined by phase-contrast magnetic resonance imaging (MRI) to assess cardiac wall movement velocities. A novel data-processing algorithm was developed to calculate regional contraction-like profiles. Using patch clamping, action potentials (AP) were recorded from cardiomyocytes isolated from the left ventricular (LV) apex and LV, septum, and right ventricular base. Cav1.2, KCNQ1, Kv1.4, Kir2.1, Nav1.5, SERCA, RyR2, Phospholamban (PLB) and NCX expression were quantified by western blot.

Results:
AP was longer in WT LV apex than in all three base regions (APD90 median 291 vs. 202, 209, 196ms; p<0.01, 0.05, 0.05). MRI revealed an earlier, longer and stronger contraction in LV apex than LV base (fig. 1) in both genotypes and an additional relaxation impairment in LQT2 LV apex (fig. 1B). In WT, 5 proteins were downregulated in LV apex vs. LV base (KCNQ1, p=0.07; Cav1.2, p<0.01; Kv1.4, NCX, PLB, p<0.05). In LQT2 no similar profile was present. Instead, NCX and PLB were upregulated apically compared to WT (p<0.05). An in silico model integrating the quantitative WT differences reproduced a contraction and AP prolongation in apex vs. base.

Conclusions:
Electromechanical heterogeneity is not exclusive to the arrhythmogenic heart: we demonstrate the presence of an electromechanical, in silico reproducible apico-basal gradient in healthy rabbit hearts with an associated regionally heterogeneous expression of 5 key proteins. This pattern can be explained logically as apical mechanical dominance reduces outflow resistance and increases efficiency. LQT2 rabbits show increased intra-cardiac heterogeneity with diastolic asynchrony that can be determined non-invasively and might have prognostic value.
Abstract 13027: Risk of Sudden Cardiac Arrest According to the Time of STEMI Occurrence: the e-MUST Study
Authors: Karam Nicole , Bataille Sophie , Tafflet Muriel , Marijon Eloi , Empana Jean Philippe , Lambert Yves , Spaulding Christian , Jouven Xavier
Published: July 2021

Introduction:
STEMI mortality decreased drastically during the last decades, and out-of-hospital sudden cardiac arrest (SCA) has become its main mode of death. The risk of out-of-hospital SCA according to the timing of STEMI occurrence has not been assessed. Hypothesis: The risk of SCA, prior to hospital admission, differs according to the timing of STEMI occurrence.

Methods:
Data were taken from a prospective pre-hospital study (e-MUST study) on all STEMI patients managed by emergency medical services in Paris and its suburbs between January 2006 and December 2010. In this area, emergency calls are routed to the closest dispatch center and regulated by physicians who send, in the field, an ambulance with a physician on board in case of suspected acute myocardial infarction. Pre-hospital EKGs are obtained for all patients and those presenting STEMI are included in the study. We assessed the rate of SCA, prior to hospital admission, according to the timing of STEMI occurrence (4 hours-time intervals starting at midnight).

Results:
Among the 8,112 STEMI patients enrolled (mean age (SD) 61.6 (14.3) years, 78% males), 452 patients (5.6%) developed out-of-hospital SCA. We observed significant circadian change in the rate of SCA per STEMI, with a progressive increase between 4am and 8pm, followed by a decrease between 8pm and 4am (P=0.0009). The peak rate of SCA per STEMI occurred in the 4pm-8pm time interval (7.7%), while the lowest rate was seen between 4am and 8am (4.2%) (Figure). Conclusions: The risk of STEMI-related SCA is almost 2-fold higher in STEMI occurring in the late afternoon hours. A better understanding of patients’ characteristics, circumstances of occurrence, and pre-hospital care is needed to eventually reduce the risk of SCA promptly after STEMI diagnosis in the field.
Abstract 13060: Prognostic Significance of Arterial Stiffness and Vascular Calcification in Patients With Coronary Artery Disease After Percutaneous Coronary Intervention
Authors: Siasos Gerasimos , Oikonomou Evangelos , Zaromitidou Marina , Maniatis Konstantinos , Kokkou Eleni , Antonopoulos Alexis , Zografos Theodoros , Mourouzis Konstantinos , Tsalamandris Sotiris , Dimitropoulos Stathis , Zisimos Konstantinos , Anastasiou Maria , Papavassiliou Athanasios G , Tousoulis Dimitris
Published: July 2021

Introduction:
Coronary atherosclerosis is the pathophysiologic background of coronary artery disease (CAD). Arterial stiffness and vascular calcification significantly contribute to coronary atherosclerosis progression.

Hypothesis:
Arterial stiffness and serum osteoprotegerin (OPG) levels are associated with cardiovascular prognosis in patients with stable CAD after percutaneous coronary intervention (PCI).

Methods:
We followed up prospectively (median time 40months), 220 consecutive subjects with stable CAD (mean age: 62±9years) after successful PCI. Carotid femoral pulse wave velocity (PWV) was measured as an index of arterial stiffness. OPG plasma levels were measured as a biomarker of vascular calcification. The primary end point was the composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke or hospitalization for cardiovascular causes.

Results:
During the follow-up period 66 patients presented the primary composite endpoint. There was no difference in age, body mass index, female gender, diabetes and hypertension, between the subjects who presented the primary end point compared to subjects free of cardiovascular events (p=NS for all). Subjects who present the primary end point compared to those free of cardiovascular events were more often active smokers (p=0.03), had higher prevalence of 3 vessels CAD (p=0.03) and lower left ventricle ejection fraction (p=0.07). Importantly, subjects who present the primary end point, compared to subjects free of cardiovascular events, had significantly increased PWV (9.45±2.48m/sec vs. 8.50±1.90m/sec, p=0.005) and OPG levels (4.21±2.19pmol/L vs. 3.12±1.74pmol/L, p=0.002). Finally, a cox regression model revealed that the primary end point was significantly associated with PWV (Hazard ratio=1.34 95%CI: 1.09-1.64, p=0.005) and OPG levels (Hazard ratio=1.23 95%CI: 1.039-1.45, p=0.02) even after adjustment for confounders such as age, sex, smoking habits, ejection fraction, extent of CAD, hypertension and diabetes.

Conclusions:
Increased arterial stiffness and vascular calcification, estimated by serum osteoprotogerin levels, are significant determinants of adverse cardiovascular events in subjects with established CAD after PCI.
Abstract 13069: Prescribed Flow Reserve as a Novel Method for Diagnosis of Coronary Artery Ischemia Under Physiologically-Realistic Conditions
Authors: Kolli Kranthi , Xiong Guanglei , Soohoo Hilary , Min James
Published: July 2021

Background.
Failure to achieve maximal hyperemia in coronary arteries during fractional flow reserve (FFR) may result in under-estimation of pressure drop (ΔP) and over-estimation of FFR, and possibly lead to misdiagnosis of hemodynamically-significant lesions. Further, induction of hyperemia does not allow for precise determination of ischemic thresholds for physiologically-realistic conditions, such as for increasing levels of exercise. We investigated the influence of prescribed flow rates on the pressure ratio (P
d
/P
a
) of coronary artery stenoses of varying severities.

Methods.
Prescribed flow reserves (PFR) were evaluated using an
in vitro
experimental flow loop with a pump circulating water at steady-state flow (Figure 1A). Three stenoses of 30%, 50% and 70% diameter stenosis (DS) severity with smooth Gaussian shapes were fabricated using VeroClear rigid material in an Objet260 Connex printer. Mean proximal pressure (P
a
) was maintained at 90 and 140 mm Hg using a linear flow needle valve that allowed for adjustment of physiologically-realistic microcirculatory resistance. P
d
/P
a
at differing prescribed flow rates (Q), titrated by a flow meter, applied to each of the stenosis, were assessed for the 2 levels of P
a
. A PFR of P
d
/P
a
≤0.80 was considered diagnostic of coronary ischemia.

Results.
The ΔP-Q characteristics demonstrated a quadratic relationship. The P
d
/P
a
-Q curve (Figure 1B and 1C) followed a similar trend, with decreasing slope. Further, the average slope of the P
d
/P
a
-Q decreased with increasing DS at either levels of the P
a
. When compared amongst lesions of increasing severity (Figure 1C and 1B), P
d
/P
a
-Q curve slopes at the 0.80 ischemic threshold increased by 9%, 20% and 25%, respectively, for 30%, 50% and 70% DS.

Conclusions.
Coronary artery ischemia, as determined by P
d
/P
a
, differs under increasing flow rates. PFR may be a potential alternative to FFR for determination of coronary ischemia under precise physiologically-realistic conditions.
Abstract 13073: Epicardial YAP/TAZ Regulate an Immune Suppressive Response Following Myocardial Infarction
Authors: Ramjee Vimal , Singh Manvendra K , Liu Feiyan , Engleka Kurt A , Manderfield Lauren J , Olson Eric N , Epstein Jonathan A
Published: July 2021

Ischemic heart disease constitutes the most prevalent type of heart disease in the US. Remodeling post-myocardial infarction (MI) is a multifaceted process driven by a strong immune response. Regulatory T-cells, a subset of CD4+ T-cells, have been shown to suppress the innate and adaptive immune response following myocardial injury to allow for less deleterious remodeling. To date, the precise mechanism by which injured myocardium recruits these suppressive immune cells remains unknown. Here, we show a novel role for the epicardium in suppressing the post-infarct inflammation response through recruitment of T-regulatory cells. The Hippo pathway is a signal transduction pathway, which has gained importance in determining organ size and is implicated as a critical regulator of tissue regeneration. Mice deficient in epicardial YAP/TAZ, two core effectors of the Hippo signaling pathway, develop profound pericardial inflammation, thoracic adhesions and myocardial fibrosis post-MI, with resultant cardiomyopathy and death. These mice demonstrate fewer suppressive T-regulatory cells in the injured myocardium, due to a deficiency of interferon-gamma, a known inducer of these T-cells. Collectively, these results suggest a novel role for Hippo signaling in immune regulation. In addition, our data suggest that the epicardium plays an important role in homing suppressive T-regulatory cells to injured myocardium so that the inflammation response may be attenuated following MI.
Abstract 13087: Are All Patients Equal in Response to Intra-Aortic Balloon Counterpulsation?
Authors: Baran David A , Cohen Marc , Visveswaran Gautam K , DiVita Michael , Seliem Ahmed , Dave Amar , Wasty Najam , Swinden Jonathan E
Published: July 2021

Background:
Intra-Aortic Balloon Counterpulsation (IABC) with a 50 cc (MEGA 50™) balloon catheter is associated with an average increase of 0.5- 0.7 liters/min in cardiac output. However, some patients (pts) have a much more dramatic response. We retrospectively analyzed our single center tertiary care experience with 150 consecutive pts undergoing IABC.

Methods:
Chart review for demographic, procedural, and hemodynamic data was collected for 150 pts of whom 64 had both pre and 4 hour post IABC hemodynamic measurements. The responder (R) group was defined by any positive change in cardiac output (CO) and cardiac index (CI) between baseline prior to IABC and 4 hours post initiation. Non-responders (NR) were defined as those with a decline in CO or no change.

Results:
IABC with a 50 cc balloon was associated with a significant improvement in CO of 0.7 L/min for the overall cohort (Pre-IABC mean CO 3.9±1.4 vs post 4.6 ±1.6 L/Min, paired t-test p=.0004). There were 38 pts in the R group (60 %) and 26 in the NR group. The CO / CI post-IABC improved significantly: CO 3.5±1.3 to 5.0±1.7 L/Min and CI 1.8±0.6 vs 2.6±0.7 L/min/M
2
) (p<0.0001). For NR pts, CO dropped from 4.5±1.3 to 3.9±1.2 L/Min (p<0.0001) and CI from 2.2±0.6 to 2.1±0.5 L/min/M
2
(p=0.1). Interestingly, systemic vascular resistance varied significantly between groups (R: 1568±657 vs NR 1218±461 (dyne*sec)/cm
5
(p=0.02). Nominal logistic regression identified pre-IABC CO as a significant predictor of response.

Conclusion:
Among a cohort of pts receiving IABC, there appears to be a binary response with “responders” augmenting CO by 1.5 L/min which is close to that provided by percutaneous ventricular assist catheters such as Impella. Patients with lower pre-IABC CO and higher SVR appear to have the most favorable response to IABC. This binary response may have influenced prior
neutral
clinical outcome trials of IABC.
Abstract 13099: Study of Right Ventricular to Pulmonary Circulation Uncoupling at Peak Exercise in Heart Failure by gas Exchange Analysis Combined to Echocardiography
Authors: Generati Greta , Bandera Francesco , Pellegrino Marta , Labate Valentina , Carbone Francesco , Alfonzetti Eleonora , Guazzi Marco
Published: July 2021

Background:
Right ventricular (RV) dysfunction and pulmonary hypertension (PH) impact on clinical status and have a prognostic value in heart (HF) patients. There is interest in assessment the RV to pulmonary circulation (PC) uncoupling during exercise even though much needs to be defined on the functional phenotypes. Aim: to define how the degrees of RV-PC uncoupling may engender specific functional phenotypes.

Methods:
94 HFrEF patients (mean age 66±11 y, male 70%, ischemic etiology 71%, mean LVEF 34±9%) underwent a maximal CPET (incremental ramp protocol) combined with exercise-echo.

Results:
Population was divided into 4 groups using the 4 quadrant approach (Figure) based on TAPSE vs systolic PAP (PASP) relationship as a length vs developed force of the RV during exercise (cutoff based on median values of 20 mm and 57 mmHg). At peak exercise patients with more favorable TAPSE vs PASP relationship (group A) showed the better functional CPET response (higher peak VO2; lower VE/VCO2 slope and prevalence of exercise oscillatory ventilation (EOV), p= 0.000, 0.005 and 0.000). Group B and C showed similar peak VO2 and the occurrence of dynamic PH (group C) was related to dynamic mitral regurgitation (MR) and high rate of EOV (B vs C p=0.001 and 0.000). Interestingly, for similar exercise tolerance and LV function parameters, group D patients had more severely impaired ventilatory efficiency associated with very high prevalence of rest severe (MR) and EOV (p=0.005, 0.002). Conclusions: This proposed non-invasive RV functional evaluation approach at peak exercise seems appealing for stageing HF syndrome severity based on the degree of the right heart dysfunction. It appears also useful to unmask different ventilatory phenotypes irrespective of a similar impairment in functional capacity and peak VO2.
Abstract 13170: Endothelial Function is Impaired in Relation to Alcohol Consumption in Men in a Large General Population
Authors: Oda Nozomu , Higashi Yukihito , Kajikawa Masato , Maruhashi Tatsuya , Iwamoto Akimichi , Kishimoto Shinji , Hidaka Takayuki , Nakashima Ayumu , Noma Kensuke , Tomiyama Hirofumi , Takase Bonpei , Yamashina Akira , Kihara Yasuki
Published: July 2021

Introduction:
Endothelial function is impaired in heavy or binge drinking. Heavy drinking should be a predictor of endothelial dysfunction. However, there is little information on the effects of dose-dependent alcohol consumption on endothelial function. Therefore, we evaluated the relationship between alcohol consumption and endothelial function in a large general population.

Methods and Results:
We measured flow-mediated vasodilation (FMD) in 2734 men who provided self-report about habitual alcohol intake. The subjects were divided into five groups by alcohol consumption: none (0 g/week), light (0 g/week< to ≤140 g/week), moderate (140 g/week< to ≤280 g/week), heavy (280 g/week< to ≤420 g/week), and excessive (420 g/week<). Age, systolic blood pressure, diastolic blood pressure, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, gamma glutamyl transpeptidase, uric acid, plasma glucose, hemoglobin A1c, and current smoking were significantly correlated with alcohol consumption. FMD showed a gradual decrease according to increased alcohol consumption (none, 6.6±3.4%; light, 6.2±3.0%; moderate, 6.0±3.0%; heavy, 5.5±2.9%; excessive, 5.3±3.0%; P<0.01). There was a significant difference in FMD between the non-drinker group and the light drinker group (P=0.018). After adjusted risk factors, we showed the significantly smaller FMD in the 4 drinker groups than in the non-drinker group: light drinker group (OR, 1.38; 95% CI, 1.10 to 1.75), moderate drinker group (OR, 1.36; 95% CI, 1.01 to 1.82), heavy drinker group (OR, 2.05; 95% CI, 1.46 to 2.87), excessive drinker group (OR, 2.04; 95% CI, 1.43 to 2.89).

Conclusions:
These findings suggest that even light alcohol consumption impair the endothelial function. Alcohol drinking may be harmful for vascular function.
Abstract 13248: Insulin Resistance as a Predictor of Coronary Artery Calcification Progression
Authors: Sung KiChul , Cheong EunSun , Lee Jong Yong , Lee Sung Ho
Published: July 2021

Introduction:
Obesity, nonalcoholic fatty liver disease (NAFLD) and insulin resistance (IR) may coexist, but it is uncertain whether these conditions contribute independently to atherosclerosis. We tested whether fatty liver, IR and obesity increase coronary artery calcium [CAC] score, a marker of atherosclerosis, independently to cardiovascular risk factors and cardiovascular disease (CVD).

Methods:
Data were analyzed from a South Korean occupational cohort of 2244 people who all received abdominal ultrasound measurements of fatty liver and non-enhanced coronary computed tomography for CAC score at baseline and follow up. IR was defined by homeostasis model assessment of IR (HOMA-IR) ≥75th percentile. Odds ratios (ORs) (95% CIs) for the presence of a CAC score >0 were estimated using logistic regression.

Results:
There were 621 people with CAC score progression. Traditional risk factor, type 2 diabetes and hypertension were independently associated with CAC progression (OR for DM 1.86 [1.17-2.95]; OR for HTN 1.43[1.04-1.96]). HOMA-IR (OR: Q4 vs Q1 1.73 [1.07-2.78]) was associated with CAC progression independently of all metabolic syndrome features, conventional cardiovascular risk factors, and prior evidence of DM and HTN. Smoking, educational status, excise frequency were not associated with CAC progression. Synergic effect had occurred with insulin resistance and obesity (OR 3.10, [1.10-8.74]) and also with obesity and fatty liver (OR 1.61, [1.03-2.53]) after adjustment of various confounding factors including age, sex, alcohol consumption, smoking status, excise frequency, degree of education, DM, HTN. The combination of presence of IR, fatty liver and obesity was associated with CAC progression (OR 3.15, [2.10-4.73]) with adjustment of age and sex. Although the association was attenuated, the combination still showed significant association after adjustment of various confounding factors (OR 2.69 [1.69-4.27]).

Conclusions:
The clustering of NAFLD, obesity and IR, is common and markedly increases the odds of CAC progression, and IR also have effects independently of each other and of confounding factors. The data suggest that treatment for each factor is needed to decrease progression of atherosclerosis.
Abstract 13275: Prognostic Impact of Impaired Admission Glomerular Filtration Rate and Subsequent Contrast-Induced Acute Kidney Injury on Adverse Cardiovascular Event in Acute Coronary Syndromes
Authors: Katayama Hisashi , Otsuka Kenichiro , Yamaguchi Tomohiro , Ishikawa Hirotoshi , Nakamura Haruo , Takeda Hisateru , Fujimoto Kohei , Kasayuki Noriaki , Yoshiyama Minoru
Published: July 2021

Introduction:
Contrast-induced acute kidney injury (CI-AKI) after percutaneous coronary intervention (PCI) is associated with adverse short- and long-term cardiovascular outcomes in patients with acute coronary syndrome (ACS). However, the association between the reduction in glomerular filtration rate (GFR) at baseline, CI-AKI, and their prognostic significance on cardiovascular outcomes has not been established.

Hypothesis:
We hypothesized that the decreased GFR on admission would be associated with cardiovascular outcomes in patients with ACS independent of CI-AKI.

Methods:
This study consists of consecutive 283 ACS patients (67±12 years old, 207 men) underwent primary-PCI. Decreased admission GFR was defined as less than 60 ml/min per 1.73m2. CI-AKI was defined as an increase of serum creatinine more than 25% within 72 hours after PCI. The primary endpoint was the occurrence of major adverse cardiovascular events (MACE) defined as cardiovascular death and non-fatal myocardial infarction.

Results:
Of the 283 ACS patients, 59 (21%) had CI-AKI. During median follow-up of 2-year, MACE was occurred in 36 (12%, 5.3% per year) patients. Multivariate Cox proportional hazard analysis demonstrated that higher age (hazard ratio [HR], 1.06, 95% confidence interval [CI], 1.02-1.11; p=0.002), decreased admission GFR (HR, 3.3, 95% CI; 1.45-8.02; p=0.004), and CI-AKI (HR, 2.5, CI, 1.10-5.65; p=0.03) were associated with MACE. Kaplan-Meier analysis demonstrated that patients with decreased admission GFR and CI-AKI presented worse outcomes compared with those without decreased admission GFR and CI-AKI (P<0.001) (Figure).

Conclusions:
Decreased admission GFR and CI-AKI were independent robust predictors of future MACE in ACS patients underwent primary-PCI.
Abstract 13281: Effect of Arteriovenous Anastomosis on Blood Pressure Reduction in Patients With Isolated Systolic Hypertension Compared to Combined Hypertension
Authors: Ott Christian , Lobo Mel D , Sobotka Paul A , Mahfoud Felix , Schmieder Roland ,   ROX CONTROL HTN Investigators
Published: July 2021

Background:
Several interventional therapeutic options for blood pressure (BP) lowering in patients with treatment-resistant hypertension (TRH) were introduced, such as renal denervation (RDN) and creation of an arteriovenous (AV) anastomosis using the ROX coupler. It was shown that BP response after RDN is greater in patients with combined hypertension (CH) compared to patients with isolated systolic hypertension (ISH). We analyzed now the effect of ROX coupler implantation in the subgroups with CH and ISH.

Methods:
The randomized, controlled, ROX CONTROL HTN study included patients with true TRH (office systolic BP ≥140mmHg, and average daytime ambulatory BP ≥135/85mmHg, despite treatment with at least 3 antihypertensive drugs including a diuretic). In our post-hoc analysis we have stratified the patients of the ROX coupler group (n=42) according CH (n=31) versus ISH (n=11).

Results:
Baseline systolic office (177±18 versus 169±17 mmHg, p=0.163) and ambulatory BP (159±16 versus 154±11 mmHg, p=0.463) did not differ between CH and ISH. Creation of an AV anastomosis resulted in a significant reduction in systolic office (CH: -28±22 versus ISH: -22±31 mmHg, p=0.572) as well as ambulatory BP (CH: -14±20 versus ISH: -13±15 mmHg, p=0.672), but without significant differences between the two subgroups. The non-responder rate (systolic office BP reduction < 10 mmHg) after 6 months was not different between the subgroups (CH: 18 % versus ISH: 23 %, p=0.844).

Conclusions:
Thus, our data suggest that creation of an AV anastomosis using the ROX coupler reduces systolic office and ambulatory BP, without any significant difference between CH and ISH. In contrast to RDN, creation of an AV anastomosis reduced BP to similar extent in both subtypes of TRH.