bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 12692: Contemporary Evidence on the Risks of Early Carotid Revascularization After Stroke in Evolution
Authors: De Rango Paola , Brown Martin , Chaturvedi Seemant , Howard Virginia , Jovin Tudor , Mazya Michael , Paciaroni Maurizio , Farchioni Luca , Caso Valeria
Published: July 2021

Introduction:
Current stroke guidelines suggest performing carotid endarterectomy (CEA) within 2 weeks after an ischemic stroke or TIA caused by severe carotid stenosis. However, early carotid revascularization in patients in unstable neurological condition after acute stroke (“stroke in evolution”, SIE) is controversial because of the risk of new ischemic stroke, intracerebral hemorrhage (ICH) and death. Published studies have not found a consistent benefit in this cohort.

Hypothesis:
The aim of this systematic review and meta-analysis was to document outcomes after urgent carotid intervention performed within 2 weeks from SIE.

Methods:
A systematic review of studies published in the last 8 years (2008-2015) reporting the risk of stroke, death and ICH following carotid intervention performed within 2 weeks from acute stroke in patients with SIE, was undertaken. Pooled proportion of periprocedural stroke, stroke or death and ICH were obtained with proportion meta-analysis and random effects model.

Results:
Out of 47 published series reporting on 2-week timing of carotid intervention after ischemic neurological event, only 15 separately described periprocedural risks for patients with SIE. In 8 studies patients underwent thrombolysis for acute stroke management of SIE before carotid revascularization. The pooled proportion of periprocedural stroke was 5.0% (95% Confidence Intervals, CI, 3.3 - 7.1), ranging 0 -14.2% among different studies. Figure. The pooled proportion of periprocedural risk for the combined of stroke or death was 4.7% (95% CI 2.9 -7.0) and that of periprocedural ICH, 1.2% (95% CI 0.4-2.4).

Conclusions:
The current risk of stroke, death and ICH after urgent carotid revascularization performed within 2 weeks for patients with stroke in evolution is lower than that anticipated in previous studies. Nevertheless, due to the heterogeneity in reporting and differential in patient selection, these findings should be interpreted with caution.
Abstract 12717: If Channel Blocker Ivabradine Counteracts Underisable Tachycardia in Patients Supported With Inotropic Agents
Authors: Levin Ricardo , Degrange Marcela , Botbol Alejandro , Levin Degrange Matias , Perez Baztarrica Gabriel , Salvagio Flavio , Porcile Rafael
Published: July 2021

Introduction:
The utilization of inotropic agents is usually linked to development of unappropriated and undesirable sinus tachycardia. That use also increases the myocardial oxygen consumption, could develop ischemic events and also has pro arrhythmic effects in coronary patients with acute heart failure, existing limited therapeutic options to face that situation.

Hypothesis:
The If channels blocker Ivabradine could be useful and safe for counteract the sinus tachycardia induced by inotropic agents and its undesirable effects without affecting the positive inotropic effect.

Methods:
Patients with ischemic-necrotic cardiomyopathy and low ejection fraction (under 35%) admitted for acute decompensation of heart failure with requirement of inotropic agents were prospectively and consecutively included.

Patients with a rhythm different than sinus rhythm, impossibility for place a Swan-Ganz catheter or unable to use the oral route were excluded. Hemodynamic measurements with Pulmonary Artery catheters were performed before and three hours after oral administration of 15mg of Ivabradine.

Results:
The study included 52 patients (32 males and 20 females) with an average age of 65.6 years and an ejection fraction of 31.5% whe were under treatment with an average dose of 15 mcg/kg of Dobutamine. Three hours after started Ivabradine, it was observed a reduction of the heart rate from 123 +/-6 to 96+/-7 beats per minute (P=0.00002) with an increment of the systolic volume from 37.9+/-5 ml to 47.3+/-8 ml (P=0.00002) and the cardiac output from 4597 +/-550 ml/minute to 4825+/-535 ml/minute (P=0.041). No differences were observed nor in the filling pressures neither in the systemic or pulmonary resistances.

There was a good clinical tolerance without evidence of hypotension, bradycardia, atrioventricular block episodes or need for transitory pacemaker .

Conclusions:
Ivabradine was an useful and safe intervention for controlling the undesirable sinus tachycardia linked to inotropic agents in patients with ischemic-necrotic cardiomyopathy. The drug didn’t affects the positive effect over contractility.
Abstract 12742: Leptin Links Acute Effects of Phosphodiesterase 4 Inhibition on Weight Loss and Energy Expenditure
Authors: Wu Chaoneng , Maiseyeu Andrei , Deiuliis Jeffrey A , Zhong Jixin , Rao Xiaoquan , Ying Zhekang , Bagalkot Vaishali , Rajagopalan Sanjay
Published: July 2021

Objective:
Leptin has been previously shown to play an important role in maintaining insulin sensitivity and energy balance via catecholamine and cAMP dependent pathways. Since inhibition of phosphodiesterase 4 (PDE4), an enzyme that potently modulates cAMP and widely expressed in innate immune cells, causes weight loss, we hypothesized that PDE4i may mediate its effects in part via shared pathways with Leptin.

Methods and Results:
Diet-induced obese C57Bl/6 (DIO) mice (12 weeks of high-fat diet, HFD, 60% fat) were treated with Roflumilast (3mg/kg/day, IP; HFD-Roflu), a high affinity inhibitor of PDE4 (PDE4i) or vehicle (HFD-Veh, n=6~10 in each group). Compared to HFD-Veh, HFD-Roflu mice showed rapid (<7 days) and substantial weight loss (% of fat content, 27.3±2.7
vs
14.5±1.6), increased energy expenditure (~20%↑ in VCO
2
,VO
2
and heat production), upregulated thermogenic genes (↑expression of
Pgc-1α
,
Ucp-1
,
Cidea
and
Dio-2
) and norepinephrine (9.5±2.0 vs 27.4±2.9 pg/g) in brown adipose tissue with corresponding upregulation of the “browning” genes in white adipose tissue (WAT). PDE4i decreased plasma leptin levels (Δ Leptin of 1.5±0.8
vs
. 16.7±4.4 in HFD-Veh
vs
HFD-Roflu from baseline to the end of treatment), with corresponding improvement in insulin sensitivity (improved ITT), hepatic steatosis and WAT inflammation (↓19.9% of CD11b
+
/F4/80
+
cells in subcutaneous WAT). However, these effects of PDE4i were not observed in Lep
ob/ob
mice when treated for the same duration with similar dose (n=6), suggesting the requisite role of leptin signaling for PDE4i effects. Simultaneous treatment of DIO mice with PDE4i and leptin-neutralizing antibody (0.4 μg/g/day, SC for 6 days) abrogated the aforementioned effects of PDE4i, while administration of Leptin (0.5 ug/g/day, IP) in addition to PDE4i in Lep
ob/ob
mice for consecutive 6 days restored weight loss and energy expenditure, improved ITT, and increased catecholamine in both WAT (6.2±0.4 vs 27.4±2.3) and BAT (14.3±1.4 vs 24.8±2.4 pg/g) previously seen in HFD-Roflu mice (n=6).

Conclusions:
Our results suggest that leptin signaling is requisite for PDE4i-induced weight loss, energy expenditure and catecholamine production in obesity.
Abstract 12757: ECG Patterns in Early Pulseless Electrical Activity and the Etiologies of In-Hospital Cardiac Arrest
Authors: Bergum Daniel , Skjeflo Gunnar W , Loennechen Jan P , Mjølstad Ole C , Nordseth Trond , Haugen Bjørn O , Skogvoll Eirik
Published: July 2021

Introduction:
The defibrillator is a mandatory diagnostic and therapeutic tool for the treatment of cardiac arrest (CA). The diagnostic potential of the defibrillator may not be fully utilized. Pulseless electrical activity (PEA) is increasingly common as the first presenting rhythm for a range of etiologies, in particular the ‘reversible causes 4H4T’ (figure). We investigated the etiology and its relation to the QRS duration and heart rate during PEA.

Method:
We conducted a prospective observational study of all CA episodes treated by an in-hospital emergency team (ET) at St.Olav University Hospital in Trondheim/Norway during 4.5 years. Two cardiologists independently examined the ECG recorded during the first compression pause after attachment of the defibrillator, and measured the duration of three consecutive QRS complexes. The averaged QRS duration was defined as normal if shorter than 120ms and the heart rate (HR) was defined as normal if between 59 and 100/minute, leading to six simple ‘patterns’ of PEA: normal, wide, narrow-slow, wide-slow, narrow-fast and wide-fast. PEA episodes with reliable causes of arrest confirmed by objective diagnostic criteria were included.

Results:
We identified 69 triggering causes in 51 PEA episodes. The figure shows the bivariate distribution of QRS/HR according to etiology, showing no obvious relationship.. In 48 episodes (83%) the initial ECGs were outside the ‘normal’ range regarding QRS duration, HR, or both. Six patients survived to hospital discharge, none of their presenting ECGs were ‘normal’

Conclusion:
Four fifths of all presenting PEA patterns were found to be abnormal with respect to HR and QRS duration. An abnormal initial ECG did not point towards etiology nore precluded survival in this modest study sample.
Abstract 12799: Left Atrial Enlargement is an Independent Risk Factor of Stroke or Systemic Embolism in Atrial Fibrillation Patients: The Fushimi AF Registry
Authors: Hamatani Yasuhiro , Takagi Daisuke , Ogawa Hisashi , Esato Masahiro , Chun Yeong-Hwa , Wada Hiromichi , Hasegawa Koji , Abe Mitsuru , Akao Masaharu
Published: July 2021

Introduction:
Atrial fibrillation (AF) is a common arrhythmic disorder and increasing significantly. Stroke or systemic embolism (SE) is a devastating complication of AF. Controversy exists regarding whether left atrial enlargement is a risk factor of stroke/SE in AF patients.

Hypothesis:
Left atrial enlargement might be associated with the incidence of stroke/SE.

Methods:
The Fushimi AF Registry, a community-based prospective survey, was designed to enroll all of the AF patients in Fushimi-ku, which represented a typical urban community in Japan. We started to enroll patients from March 2011, and follow-up data were available for 2,724 patients by April 2015 (median follow-up period 808 days). Left atrial enlargement (LAE) was diagnosed if the left atrial diameter measured by transthoracic echocardiography was >45 mm. We compared the backgrounds and incidences of events during follow-up period between those with LAE and those without it (non-LAE).

Results:
Backgrounds and incidences of events between LAE and non-LAE are shown in the Table. LAE group showed higher incidence of stroke/SE during follow-up period, compared with non-LAE group (hazard ratio (HR): 1.81, 95% confidence interval (CI): 1.29-2.57, p<0.01). After adjustment by the components of CHADS2 score and oral anticoagulant prescription, LAE was independently associated with higher risk for stroke/SE (HR: 1.70, 95% CI: 1.20-2.43, p<0.01). This was also the case when we defined cut-off as 40 mm (HR: 1.67, 95% CI: 1.12-2.55, p=0.01), and as 50 mm (HR: 1.58, 95% CI: 1.08-2.29, p=0.02), or we analyzed left atrial diameter as continuous variables (HR (per 1mm): 1.03, 95% CI: 1.01-1.05, p<0.01). Even after adjustment by type of AF (paroxysmal or sustained) and valvular heart diseases, LAE remained to be independently associated with the risk of stroke/SE (HR: 1.57, 95% CI: 1.08-2.31, p=0.02).

Conclusion:
Left atrial enlargement was independently associated with the increased risk of stroke/SE in AF patients.
Abstract 12805: Postnatal Progressive Atrioventricular Block By Heterozygous Nkx2-5 Homeodomain Missense Mutation With Atrioventricular Nodal Atrophy
Authors: Ashraf Hassan , Chowdhury Rajib , Melanson Michelle , Tanada Yohei , Nguyen Minh , Silberbach G. Michael , Wakimoto Hiroko , Benson D.Woodrow , Anderson Robert , Kasahara Hideko
Published: July 2021

Introduction:
Heterozygous human NKX2-5 homeodomain (DNA binding domain) missense mutations are highly penetrant for varied cardiac anomalies and progressive atrioventricular block (AVB). We replicated many elements of the cardiac anomalies in a murine heterozygous knock-in model (Nkx2-5+/R52G, hereafter Nkx2-5-KI) in a 129/Sv background.

Hypothesis:
We hypothesized that Nkx2-5-KI mice demonstrate progressive AVB during postnatal life similar to human patients.

Methods:
Nkx2-5-KI mouse model and control Nkx2-5+/+ mice were analyzed by histopathology, surface and telemetry ECG, and in vivo electrophysiology studies (EPS), and compared at postnatal day 1 (P1) to 17 months. We re-evaluated a pedigree of a human family having Arg52(189)Gly mutation in 5 generations.

Results:
Nkx2-5-KI mice demonstrated PR-prolongation (1st degree AVB) at 4 weeks, 7 months, and 17 months of age but not at P1 (control n=35, mutant n=38). Advanced AVB was occasionally observed. EPS showed that AV node function, and right ventricular effective refractory period were impaired in Nkx2-5-KI mice, while sinus node function was normal. AV node size was significantly smaller in Nkx2-5-KI mice relative to control mice (maximum area size 2.4 ± 0.2 vs. 1.6 ± 0.1 x 10-2 mm2, 36% reduction; calculated volume 1.50 ± 0.1 vs. 1.11 ± 0.03 x 10-4 mm3, 24% reduction, n=6 each) at 4 weeks of age but not P1, similar to age-dependence of PR-prolongation. AV node in mutant mice was composed of smaller cardiomyocytes without fibrosis, suggesting in part, that conduction abnormalities are the result of an AV node that becomes morphologically atrophic during postnatal life. All 6 genotype-positive humans demonstrated AVB (1st, 2nd, and 3rd degree). QRS prolongation was uniquely demonstrated in Nkx2-5-KI mice from the neonatal stage onward but not in human patients, suggesting substantial discordance in ventricular conduction system between mouse and human.

Conclusion:
Highly penetrant and progressive AVB similar to that seen in humans with heterozygous NKX2-5 homeodomain missense mutations was replicated in mice by knocking-in a comparable missense mutation. The progressive AVB phenotype is likely due to an AV node composed of smaller cardiomyocytes that becomes atrophic during postnatal life.
Abstract 12875: Serum Neutrophil Gelatinase-associated Lipocalin Has a Predictive Value for the Neurological Outcome of Post Cardiac Arrest Victims
Authors: Kaneko Tadashi , Fujita Motoki , Ogino Yasuaki , Irie Hiroki , Iwashita Shinsuke , Karashima Ryuichi , Kamikawa Masashi , Tanaka Hiromichi , Tsuruta Ryosuke , Kasaoka Shunji
Published: July 2021

Introduction:
Neutrophil gelatinase-associated lopocalin (NGAL) is well known as the biomarker of acute kidney injury. Currently, serum NGAL is reported as the biomarker which is associated with mortality and multiple organ dysfunction syndrome in septic patients. In this study, we measured serum NGAL in post cardiac arrest syndrome (PCAS) patients to investigate the predictive value of neurological outcome.

Hypothesis:
Serum NGAL is associated with favorable neurological outcome of PCAS patients.

Methods:
43 cases of PCAS patients were measured serum NGAL on day 1 and 2, and serum neuron specific enolase (NSE) was also measured on day 2. Patients were divided into two group (group G: CPC 1-2 and group P: CPC 3-5, CPC: cerebral performance categories). Serum NGAL and NSE were compared between group G and P. Receiver operation characteristic (ROC) curve analysis were performed of both NGAL and NSE.

Results:
Group G (n = 20) and P (n = 23) were analyzed. Serum NGAL showed significant difference in day 2 (G: 282±116 ng/mL v.s. P: 299±87 ng/mL in day1: P = 0.609, G: 185±124 ng/mL v.s. P: 353±110 ng/mL in day 2: P<0.001). The ROC curve analysis showed area under the curve of NGAL in day 2 was 0.871, and the area of NSE in day2 showed 0.918.

Conclusions:
Serum NGAL in PCAS patients had the predictive value for neurological outcome which is comparable to serum NSE.

(This study was supported by grants from Japanese Ministry of Health, Labour and Welfare: No. 25462824)
Abstract 12911: Metformin Preserves ATP Concentration, Attenuates Action Potential Shortening, and Prevents Ventricular Fibrillation During Low-flow Ischemia in Normal Hearts
Authors: Schwartz Gregory G , Lu Li , Ye Shuyu , Greyson Clifford R
Published: July 2021

Introduction:
Metformin (MET) is the most common drug used to treat type 2 diabetes, in part because it is believed to reduce cardiovascular mortality. However, it is unknown whether MET provides protection from ischemic ventricular fibrillation (VF) in the normal heart. In a region of ischemic myocardium, reduced energy charge causes ATP-sensitive potassium channels to open, shortening the action potential (AP). The resulting dispersion of AP duration and refractoriness may predispose to VF. We determined effects of MET on myocardial ATP concentration, AP, and VF during regional ischemia in metabolically normal pigs.

Methods:
Normal domestic pigs were treated with a clinically relevant dose of MET (30 mg/kg/d, n=25) for 2-3 weeks and compared with untreated controls (CTL, n=23). Under anesthesized, open-chest conditions, phospho-AMP activated protein kinase (pAMPK, Thr172) was measured in myocardial biopsies taken before ischemia (n=8 each group). Low-flow ischemia was induced by 50% LAD flow reduction. [ATP] was measured in myocardial biopsies at 15 min ischemia (MET n=8, CTL n=7). Monophasic AP was recorded at baseline and at 15 min ischemia. Survival free of VF was observed during 90 min of ischemia and 45 min reperfusion.

Results:
pAMPK was 85% greater in MET than in CTL (p<0.001), establishing a myocardial effect of MET prior to ischemia. MET had no effect on non-ischemic AP duration. At 15 min ischemia, [ATP] was higher in MET than CTL (4.1 vs 3.5 μmol/g, p=0.039), with less AP shortening from baseline in MET (4±2%) than in CTL (13±2%, p<0.001). Survival free of VF was greater in MET pigs than CTL (Figure).

Conclusions:
Chronic treatment with a clinically relevant dose of MET activates AMPK, preserves [ATP] and prevents AP shortening during ischemia, and diminishes the propensity for ischemic VF in metabolically normal pigs. Based on these findings, MET may have therapeutic utility beyond type 2 diabetes, extending to ischemic protection of the normal heart.
Abstract 12930: Low Urine Sodium (UNa) Early After Heart Failure Admission Predicts Long Length of Stay and Early Mortality
Authors: Luk Adriana , Groarke John D , Gopal Deepa M , Joyce Emer , Shah Sachin P , Desai Akshay , Lakdawala Neal , Stevenson Lynne
Published: July 2021

Background:
Although decongestion is the primary focus of acute heart failure (HF) management, the degree of natriuretic response to diuretic therapy varies and may predict length of stay (LOS) and early outcomes. We hypothesize that a UNa <60 mmol/L, measured after initial intravenous (IV) diuretic administration, would be associated with longer duration of IV diuretic, longer LOS, increased use of inotropic therapy in hospital and higher risk of death.

Methods and Results:
From July 1, 2014-May 30, 2015, we enrolled 100 unique patients hospitalized to the advanced HF service for decompensated HF. Dose of IV diuretic was based on their daily oral home dose. Spot urine samples were collected within a median of 98 (0-187) minutes after initial diuretic therapy. Patients with UNa <60 mmol/L (n=30) had significantly lower serum sodium and higher admission NT-proBNP than those with UNa >60 mmol/L (n=70). As well, they were more commonly rated with hemodynamic profile C (“cold and wet”, 40.0 vs.11.4%, p=0.002) and INTERMACS profile 3-4 (30.0 vs. 12.9%, p= 0.04). During the hospital stay, patients with low initial UNa required longer use of IV diuretic therapy (9.5 vs. 5.0 days, p<0.0001) and had a longer median LOS (12.0 vs. 6.0 days, p< 0.0001) than those with high UNa. After adjusting for eGFR, UNa <60 mmol/L was still associated with a higher likelihood of inotropic usage in hospital (hazard ratio [HR] 9.91 (3.27-30.05); p<0.0001) and death (HR 3.14 (1.20-8.23); p=0.004) at a median follow-up period of 85 (38-159) days (figure 1).

Conclusions:
Low UNa after initial IV diuretic administration identifies a population of acute HF patients with advanced disease who have longer LOS and are at high risk for death. Measurement of UNa after first diuretic therapy may help to facilitate triage of patients with heart failure and anticipate the need for advanced HF therapies
Abstract 12975: Cardiac I-123 Metaiodobenzylguanidine Imaging Predicts the Risk of Cardiac Death in Patients With Chronic Heart Failure, Irrespective of Blood Urea Nitrogen to Creatinine Ratio: A Long-Term Follow Up Study
Authors: Hakui Hideyuki , Yamada Takahisa , Motrita Takashi , Furukawa Yoshio , Tamaki Shunsuke , Iwasaki Yusuke , Kawasaki Masato , Kikuchi Atsushi , Kondou Takumi , Ishimi Masashi , Ozaki Tatsuhisa , Sato Yoshihiro , Seo Masahiro , Ikeda Iyo , Fukuhara Eiji , Fukunami Masatake
Published: July 2021

Background:
Cardiac I-123 metaiodobenzylguanidine (MIBG) imaging, which reflects cardiac sympathetic activity, provides prognostic information in patients with chronic heart failure (CHF). On the other hand, elevated blood urea nitrogen to creatinine ratio (BUN/Cr), a surrogate for renal neurohumoral activation, is associated with poor outcome in patients with heart failure. However, there is no information available on the prognostic value of cardiac MIBG imaging in patients with CHF, relating to BUN/Cr.

Methods:
We studied 109 CHF outpatients (NYHA class:2.1±0.6, ischemic origin:52%) with left ventricular ejection fraction <40% (30±8%) in our prospective cohort study. At the enrollment, we measured serum level of BUN and Cr, and performed cardiac MIBG scintigraphy. Elevated BUN/Cr was defined as >20. The cardiac MIBG washout rate (WR) was calculated from the chest anterior view images obtained at 20 and 200 min after isotope injection. Abnormal WR was defined as >27%.

Results:
Forty patients had elevated BUN/Cr, and 55 patients had abnormal WR. During a follow up period of 7.5±4.2 yrs, 36 of 109 patients had cardiac death. At multivariate Cox analysis, WR was significantly independently associated with cardiac death in group with both elevated BUN/Cr (p=0.02) and normal BUN/Cr (p=0.004). Kaplan-Meier analysis showed that patients with abnormal WR had a higher risk of cardiac death than those with normal WR, in group with both elevated BUN/Cr (48%[11/23] vs 6%[1/17], p=0.02, adjusted hazard ratio 11.8[95%CI 1.5-92.2]) and normal BUN/Cr (55%[18/33] vs 17%[6/36], p=0.001, adjusted hazard ratio 4.6[95%CI 1.8-11.6]).

Conclusion:
The cardiac MIBG imaging could predict the risk of cardiac death in CHF, irrespective of BUN/Cr.
Abstract 13048: The Impact of Statin-Ezetimibe Combination Therapy in Patients With Decreased Cholesterol Absorption Ability
Authors: Yamanaga Kenshi , Tsujita Kenichi , Sugiyama Seigo , Sumida Hitoshi , Shimomura Hideki , Yamashita Takuro , Komura Naohiro , Sakamoto Kenji , Oka Hideki , Nakao Koichi , Nakamura Sunao , Ishihara Masaharu , Matsui Kunihiko , Skaino Naritsugu , Nakamura Natsuki , Yamamoto Nobuyasu , Koide Shunichi , Matsumura Toshiyuki , Fujimoto Kazuteru , Tsunoda Ryusuke , Morikami Yasuhiro , Matsuyama Koushi , Oshima Shuichi , Kaikita Koichi , Hokimoto Seiji , Ogawa Hisao
Published: July 2021

Introduction:
Ezetimibe (EZE) is a cholesterol absorption inhibitor and its clinical benefit, as combined with statin for pts with coronary artery disease (CAD), was shown by IMPROVE-IT trial. Campesterol (camp) is the cholesterol absorption marker and the benefit of EZE/statin combination therapy for pts with low camp (LC) value, in whom EZE appears to ineffective, is not clearly understood. The PRECISE-IVUS (Plaque REgression with Cholesterol absorption Inhibitor or Synthesis inhibitor Evaluated by IntraVascular UltraSound) trial was a prospective, randomized, controlled, multicenter study evaluating the effects of EZE addition to atorvastatin (atorva), compared with atorva monotherapy, on coronary atherosclerosis evaluated by IVUS and lipid profile.

Hypothesis:
In this study, we investigated the effect of EZE for pts with the LC value.

Methods:
246 pts undergoing IVUS-guided percutaneous coronary intervention were randomized to EZE/atorva combination (EA) group or atorva alone (A) group. The dosage of atorva was uptitrated with a treatment goal of lowering low-density lipoprotein cholesterol (LDL-C) below 70mg/dL. Serial volumetric IVUS was performed at baseline and 9–12 months follow-up to quantify the coronary plaque response in 202 patients.

Results:
There were significantly positive correlation between baseline LDL-C level and baseline camp value (R=0.399, p<0.01), but no significant difference between baseline camp value and the presence of prior statin use. Baseline LDL-C level was significantly lower in LC groups (LC group vs. high camp group; 100.2±25.5mg/dL vs. 116.8±23.5mg/dL, respectively, p<0.0001). In the LC group, the delta LDL-C ratio (follow up LDL-C - baseline LDL-C / baseline LDL-C) was significantly lower in EA group compared with A group (-37.2±16.2% vs. -23.4±25.1%, p=0,009) and EA group showed significantly greater reduction in delta percent atheroma volume, compared with A group (-2.2 [-4.1 to -0.1]% vs. -0.3 [-1.6 to 1.1]%, p=0.04).

Conclusions:
Even in pts with CAD and LC value, statin-EZE combined therapy showed significantly decreased LDL-C and regressed coronary plaque burden. Even if the cholesterol absorption ability is declined, EZE-statin combined therapy might be the promising option for pts with CAD.
Abstract 13081: Large Volume Intra-Aortic Balloon Counterpulsation: Efficacy and Safety of the
Mega 50cc
in 150 Consecutive Patients
Authors: Visveswaran Gautam K , Cohen Marc , Divita Michael , Seliem Ahmed , Dave Amar , Swinden Jonathan E , Wasty Najam , Baran David A
Published: July 2021

Background:
Intraaortic balloon counterpulsation (IABC) with the larger volume (LV) 50 cc
Mega
balloon offers greater aortic diastolic augmentation and systolic unloading than its 40cc predecessor. We retrospectively analyzed our single center tertiary care experience with 150 consecutive patients (pts) with LV IABC to gauge its efficacy and safety.

Methods:
Retrospective chart review for demographic, procedural, safety and in-hospital outcome data was undertaken on 150 pts. In 64 pts, hemodynamic data by Swan was available pre- IABC, and 4, 24, and 48 hours during IABC.

Results:
LV IABC was deployed for cardiogenic shock and/or CHF (n=128), coronary ischemia (n=11), or high risk PCI/surgery (n=11): Mean age 58±15 with 18% over age 80, 21% female, 36% % African-American. The median LVEF was 22% (15.3%-33.2%) and 37% were non-ischemic myopathy. 19% of IABC insertions were emergent at bedside without fluoroscopy. Median duration of IABC was 92 hrs (48hrs-235 hrs) during which a leak or poor augmentation developed in 3%. 3(2%) pts had major vascular complications; 3(2%) pts had major bleeding. 51(34%) pts escalated from IABC to Impella, LVAD, or heart transplantation. Overall, in-hospital mortality was 27%. In the subgroup of 100 pts in whom IABC was the initial therapy for cardiogenic shock mortality was only 32%. Hemodynamic data (64 pts) pre-IABC vs 48 hrs: Aortic systolic pressure decreased (mean systolic unloading) -10.7 +/-25 mmHg; absolute Aortic diastolic pressure (augmented dias AoP) 108 ± 22mmHg; mean PA decreased -5.4±11; mean RA -3.2±6 (all p <0.05). Cardiac output and index increased by of 0.7±1.6 l/min, and 0.4±0.8 l/min/m2 respectively (p<0.005).

Conclusion:
LV IABC with the 50cc
Mega
balloon is a safe first line percutaneous support strategy in critically ill pts with easy bed-side deployment and relatively few device related complications. Despite conflicting results from clinical trials, we observed, a significant improvement in hemodynamic indices in a broad range of pts with relatively few vascular and bleeding complications with IABC. Among the 100 pts in whom IABC was the initial ventricular assist therapy for cardiogenic shock, survival to hospital discharge was 68%.
Abstract 13103: A Novel Anchor Protein TUG Mediates GLUT4 Translocation by AMP-activated Protein Kinase in the Ischemic Heart
Authors: Ma Yina , Sun Wanqing , Quan Nanhu , Wang Lin , Chen Xingchi , Bogan Jonathan , Li Ji
Published: July 2021

Introduction:
Ischemic heart disease is a leading cause of death, and it is caused by reduced blood flow to the ischemic area. Thus, an increasing nutrient uptake is a key approach to increase cardiomyocyte survival rate during the ischemia and reperfusion (I/R) period. TUG (tether containing a UBX domain, for GLUT4, 60 KDa) is a regulator of GLUT4 trafficking, it can be cleaved to mobilize GLUT4 from intracellular membranes to the cell surface after insulin stimulation in skeletal muscle. The energy sensor AMP-activated protein kinase (AMPK) is known to play an important cardioprotective role during myocardial I/R by regulating GLUT4 translocation and glucose uptake.

Hypothesis:
TUG is one of the downstream targets of AMPK, which can be phosphorylated by hypoxia/ischemia induced AMPK activation. Phosphorylation of TUG accelerates its cleavage and increases GLUT4 translocation during ischemia/reperfusion in the heart.

Methods:
In vitro
hypoxia chamber and
ex vivo
isolated mouse heart perfusion Langendorff system were used to test the hypothesis. Antithrombin (AT) is an endogenous AMPK agonist in the heart, which was used to define the role of TUG in regulating GLUT4 trafficking during ischemia and reperfusion in the heart.

Results:
The
ex vivo
heart perfusion data demonstrated that AT triggered AMPK activation and significantly increase glucose uptake and GLUT4 translocation during ischemia and reperfusion (p<0.05 vs. vehicle). Intriguingly, GLUT4 immunoprecipitation data showed that AT treatment caused a dissociation of TUG from GLUT4. Moreover, AT treatment increased abundance of a TUG cleavage product (42 KDa) in response to I/R. All of these glucose transporter trafficking events are blunted in the AMPK kinase dead (KD) transgenic hearts. In HL-1 cardiomyocytes, TUG proteins were phosphorylated by activated AMPK during hypoxia. Moreover, TUG siRNA knockdown the TUG of HL-1 cells caused significantly increased cell surface GLUT4 and glucose uptake.

Conclusions:
Cardiac AMPK activation stimulates TUG cleavage and causes the dissociation between TUG and GLUT4 in the intracellular vesicles. TUG is a critical mediator that modulates cardiac GLUT4 translocation to cell surface and enhances glucose uptake by AMPK signaling pathway.
Abstract 13104: Comparison of Patient Characteristics and Outcomes Between Adult Non-traumatic Out-of-hospital Cardiac Arrests With and Without Extracorporeal Cardiopulmonary Resuscitation - A Community-wide Evaluation
Authors: Ko Patrick Chow-In , Chou Nai-Kuan , Ma Matthew Huei-Ming , Chen Yu-Wen , Wang Tzong-Luen , Chang Wen-Han , Kao Wei-Fong , Wu Young-Long , Lee Bin-Chou , Chen Ying-Ju , Yang Mei-Fen , Liu Yueh-Ping , Lin Hsien-Tang , Lin Chi-Hung , Chiu Allen Wen-Hsiang , Chen Yih-Sharng
Published: July 2021

Objectives:
The outcome of patients after OHCA is poor. Return to spontaneous circulation (ROSC) dramatically decreases with the duration of CPR. Extracorporeal membrane oxygenation has been proposed to assist CPR (ECPR) in OHCA. This study was to investigate the effects and characteristics of ECPR for adult non-traumatic (ANT) OHCA versus Non-ECPR on a community-wide basis.

Methods:
A prospective four-year observational database collected from a community-wide OHCA web registry in an urban EMS (emergency medical services) was studied. The EMS ambulance teams were capable with advanced airway, intravenous (iv) fluid skills, basic and advanced life support and automated external defibrillator techniques. Outcomes included survival and cerebral performance category scale (CPC) at discharge. ANT OHCA with and without ECPR in emergency were compared by regression analysis including factors of patient, pre-hospital and hospital characteristics and outcomes.

Results:
Comparing OHCA receiving ECPR (n=79) to those without (n=959), ECPR group were younger (median age 56 vs 78 p<0.001) and had higher portion for men (89 vs 64% p<0;001), witnessed arrest (Wit) (60.8 vs 32.5% p<0.001), bystander CPR (BCPR) (53.2 vs 36.8% p=0.005), initial shockable rhythms (SR) (74.6 vs 12.2% p<0.001) and therapeutic hypothermia (TH) (22.8 vs 1.1%, p<0.001). They (EPCR vs non-ECPR) had no difference for prehospital time intervals (22.5 vs 23 min.), laryngeal mask airway treatment (55.7 vs 52.8%), EMS iv epinephrine (20.3 vs 15.5%), endotracheal intubation (6.3 vs 8.0%), prehospital ROSC (11.4 vs 6% p=0.09), and ROSC upon hospital arrival (10.1 vs 8.5%). Outcomes were better in ECPR for discharged survival (41 vs 7% p<0.001) and CPC 1or2 (20.8 vs 3.8% p<0.001). After adjusting for Wit, BCPR, SR, TH, age and sex, both survival (adjusted odds ratio: 3.6 [95% 2.0-6.6]) and good CPC 1or2 (adjusted OR: 2.9 [95% 1.2-6.9]) were still significantly higher in ECPR.

Conclusions:
In current emergency practice for ANT OHCA, ECPR tended to apply to patients of younger age, men, witnessed arrest, BCPR, and initially shockable rhythms regardless of positive ROSC upon hospital arrival, that can independently lead to higher survival and good neurological outcome compared to non-ECPR.
Abstract 13113: Identification of Novel Copper-dependent Wound Repair Mechanism: Role of Copper Transport Protein Antioxidant 1
Authors: Das Archita , Chen Gin-Fu , Kim Ha Won , Varadarajan Sudhahar , Youn Seock-Won , Yang Jay , Finney Lydia , Ushio-Fukai Masuko , Fukai Tohru
Published: July 2021

Copper (Cu) facilitates wound healing and angiogenesis with unknown mechanism. Bioavailability of Cu is controlled by transport-proteins, including cytosolic Cu-chaperone Atox1, which is required for activation of secretory Cu enzymes. Atox1 also functions as a Cu-dependent transcription factor, but its role in wound healing is unknown. Using mouse skin puncture model, here we show that Atox1 protein (8-fold) and Cu-level (by X-ray Fluorescence Microscopy; 2.5-fold) were increased in wounding tissue in wild type (WT) mice at day 7 when Atox1 was localized in nucleus of dermal endothelial cells (ECs) as well as cytosol of epidermal cells, granulation tissue. Furthermore, topical Cu treatment enhanced (20% vs PBS), but specific Cu chelator BCS reduced wound repair in WT mice. Importantly, Atox1 knockout (KO) mice showed abolished topical Cu-induced wound repair or impaired endogenous wound healing vs. WT mice, which was associated with decreased angiogenesis (CD31+, 45% ), proliferation (BrdU+, 60%), ROS-production (DHE+), collagen formation (Masson's Trichrome), and infiltration of macrophage (Mac3+,40%) which secrets angiogenic cytokines VEGF and SDF-1α. Mechanistically, Atox1KO mice exhibited reduced wounding-induced expression of Atox1 target proteins such as p47phox NADPH oxidase and cyclin D1 as well as extracellular matrix secretory Cu-enzyme lysyl oxidase activity. Finally, bone marrow (BM) transplantation revealed that Atox1 in both BM and tissue resident cells are required for wound repair. Consistently, Atox1 protein and Cu were markedly increased in WT-BM tissue after wounding. Impaired wound healing in Atox1 KO mice was rescued by both Atox1-gene transfer and WT-BM topical treatment in wound tissues. In summary, Atox1 senses Cu to accelerate wound healing/repair by promoting angiogenesis, inflammatory cell recruitment, proliferation, extracellular matrix maturation as well as BM cell function. Taken together, Cu-Atox1-based therapy may represent a novel therapeutic strategy to promote dermal wound healing and tissue regeneration.
Abstract 13134: Impact of the American Heart Association’s 2007 Guidelines on the Practice of Dental Prophylaxis for the Prevention of Infective Endocarditis in Olmsted County, Minnesota
Authors: DeSimone Daniel C , El Rafei Abdelghani , Carr Alan B , Rocca Walter A , St. Sauver Jennifer , Lahr Brian D , Steckelberg James M , Wilson Walter R , Baddour Larry M
Published: July 2021

Background:
In 2007, the American Heart Association (AHA) infective endocarditis (IE) prevention guidelines recommended that antibiotic prophylaxis before invasive dental procedures for the “moderate risk” (MR) group, which represented the bulk of patients who were to receive prophylaxis before 2007, be eliminated. This decision was met with much concern among some healthcare providers and that concern persists today. We therefore evaluated dental office records in Olmsted County (OC), Minnesota to determine whether patients included in the MR group continue to receive antibiotic prophylaxis despite the 2007 AHA recommendations.

Methods:
Eligible patients include all adult (≥18 years) residents of OC, classified as having MR cardiac condition for IE (i.e. mitral valve prolapse [MVP], bicuspid aortic valve [BAV], hypertrophic obstructive cardiomyopathy [HOCM], acquired valvular dysfunction [AVD]), with at least one dental visit between January 1, 2005 and June 1, 2015. Eight dental offices located within OC were sampled to identify both dental procedures and whether antibiotic prophylaxis was administered according to AHA guidelines.

Results:
We identified 334 MR patients. Approximately 62% of MR patients received antibiotic prophylaxis prior to the change in AHA guidelines in 2007. There was a decrease to 7% post-2007 AHA guidelines (P<.001). The magnitude of decline was greater among visits for dental cleanings (from 63% to 6%), as compared to other invasive procedures (57% to 11%; P=0.003) (Figure 1). AVD was the most common cardiac condition (85%), followed by MVP (8%), and BAV (4%).

Conclusion:
Following publication of the 2007 AHA IE prevention guidelines, there was a rapid, 9-fold decrease in antibiotic prophylaxis in patients with MR cardiac conditions who underwent invasive dental procedures in OC. These data are also critical as we attempt to evaluate the impact, if any, of this practice on the incidence of IE due to viridans group streptococci.
Abstract 13144: Comparison of Risk Scores for the Prediction of Stroke in African Americans: Findings From the Jackson Heart Study
Authors: Foraker Randi E , Greiner Melissa A , Sims Mario , Tucker Katherine L , Bidulescu Aurelian , Shoben Abigail B , Smith Sakima , Talegawkar Sameera , Blackshear Chad , Wang Wei , Hardy Chantelle , Towfighi Amytis , O'Brien Emily
Published: July 2021

Introduction:
Evidence from existing cohort studies supports the prediction of incident coronary heart disease and stroke using 10-year cardiovascular disease (CVD) risk scores and the American Heart Association/American Stroke Association’s cardiovascular health (CVH) metric.

Hypothesis:
The predictive ability would be similar between the two scoring systems for incident stroke among African-American participants of the Jackson Heart Study.

Methods:
We included all participants with complete scoring information at baseline who had no history of stroke (n=4,140). We used Kaplan-Meier methods to calculate the cumulative incidence of stroke, and estimated hazard ratios and 95% confidence intervals (CI) for stroke according to CVD risk and CVH score. We compared the discrimination of the two models according to the Harrell c-index and predicted versus observed stroke risk calibration plots.

Results:
The average age of the participants was 54.5 years, and 65% were female. The cumulative incidence of stroke increased across worsening categories of CVD risk and CVH (Figure). A one-unit increase in CVD risk increased the hazard of stroke (1.07, 1.06-1.08), while each one-unit increase in CVH corresponded to a decreased hazard of stroke (0.76, 0.69-0.83). As evidenced by the c-statistics, the CVH model was less discriminating than the CVD risk model 0.59 (0.55-0.64) versus 0.79 (0.76-0.83). However, both models had poor calibration in the uppermost and lowermost deciles of risk.

Conclusions:
While the CVD risk model was more discriminating than the CVH model, both scores were associated with incident stroke in a dose-response fashion. The CVH score has the advantage of simplicity in application to broad patient populations. However, by including estimates of physical activity and diet, the CVH provides a basis from which to make recommendations on behavior change.

Figure. Kaplan-Meier curves for incident stroke by categories of CVD risk (left) and CVH (right).
Abstract 13148: Combined Association of Conventional Cardiovascular Risk Profile and Coronary Artery Calcium Score (CAC) With Cardiovascular Risk and CAC Progression: The St Francis Heart Study
Authors: Waheed Salman , Reichek Nathaniel , Guerci Alan , Cao Jie J
Published: July 2021

Objective:
Both coronary artery calcium (CAC) and clinical risk profile (RP) predict cardiovascular (CV) risk. Little is known about the association of combined CAC and RP with risk of CV outcomes and CAC progression.

Methods:
We followed 1,225 asymptomatic adults from the observational arm of the St Francis Heart Study for a median of 3.9 years. Participants were categorized into four groups based on CAC and RP (using 2013 AHA guidelines for statin eligibility): group 1 (N=336) CAC<80
th
percentile (for age and gender), statin not indicated; group 2 (N=350) CAC<80
th
percentile, statin indicated; group 3 (N=209) CAC≥80
th
percentile, statin not indicated and group 4 (N=330) CAC≥80
th
percentile, statin indicated. We compared the risk among groups for a composite CV outcome that included non-fatal MI, coronary death, coronary revascularization, stroke and peripheral arterial revascularization. We also examined the association of groups with CAC progression at four years from baseline.

Results:
Mean age was 59±6 years. Those eligible for statin were older (61±5 vs 55±5 years) and more likely to be male (82% vs.51%) than those not eligible. Median [IQR] CAC was higher in statin eligible than in noneligible subjects, 0 [0-7] vs. 9 [0-54] for groups 1 and 2 and 210 [115-404] vs. 482 [257-837] for groups 3 and 4. Adjusted hazard ratio (95% CI) for the composite CV outcome was 6.9 (0.8-58.9), 15.2 (1.9-119.3), and 37.8 (4.8-297.2) for groups 2, 3 and 4, respectively compared to group 1. There was a higher progression of CAC from baseline to year 4 among group 3 (median: 210 to 350) and group 4 (482 to 822) compared to group 1 (0 to 3) and group 2 (9 to 16), P<0.001.

Conclusion:
While higher CAC is associated with greater CV outcome risk and CAC progression, statin therapy eligibility is associated with a higher CV outcome risk both among those with and without elevated CAC. Our findings suggest that RP remains important and should not be overlooked when CAC testing is used.
Abstract 13257: FEV1 and FVC predict Mortality in Individuals Without Manifest Lung Disease Independent of Cardiac Performance - Results From the Population-based Gutenberg Health Study
Authors: Baum Christina , Ojeda Francisco M , Wild Philipp S , Rzayeva Nargiz , Zeller Tanja , Sinning Christoph R , Pfeiffer Norbert , Beutel Manfred , Blettner Maria , Lackner Karl J , Blankenberg Stefan , Munzel Thomas , Rabe Klaus F , Schnabel Renate B
Published: July 2021

Background:
Pulmonary disease has consistently been related to increased mortality. We investigated central spirometry variables in relation to total mortality in individuals from the general population without diagnosed lung disease also accounting for cardiac function.

Methods:
In 15,010 individuals from the general population (mean age 55±11 years, age range 35-74 years, 50.5% men) in the Gutenberg Health Study we performed spirometry and multimodal transthoracic echocardiography. The biomarkers N-terminal pro-B-type natriuretic peptide (Nt-proBNP) and high-sensitive troponin I (TnI) were measured in the first 5000 individuals using commercially available assays. Multivariable Cox regression analyses were computed for the lung function parameters forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC) and the Tiffeneau-Pinelli index (FEV1/FVC ratio) after exclusion of individuals with prevalent pulmonary disease (N=1135).

Results:
The median FEV1/FVC ratio was 79.1%, 19.5% were current smokers, 4.2% had prevalent heart failure. After a median follow-up of 5.5 years 360 deaths were recorded. Multivariable-adjusted Cox regression analyses for the common cardiovascular risk factors (age, sex, body mass index, current smoking, diabetes mellitus, hypertension, dyslipidemia) and heart failure revealed that an increase of one standard deviation (SD) of FEV1 was associated with a 38% risk reduction (hazard ratio (HR) per SD 0.62 [95% confidence interval (CI): 0.52-0.73]). The association remained statistically highly significant after additional adjustment for ejection fraction, stroke volume, Nt-proBNP or TnI. Comparable results were seen for FVC, whereas no association of FEV1/FVC ratio with mortality could be shown. No significant interaction by heart failure was observed.

Conclusions:
The central lung function parameters FEV1 and FVC were related to all-cause mortality in individuals without manifest lung disease. Our findings indicate that subtle, subclinical pulmonary impairment constitutes a risk for increased mortality independent of cardiac performance.
Abstract 13306: Combined Assessment of Acute Kidney Injury and Increased Plasma Concentration of D-dimer Is Useful for Evaluating 1-year Mortality in Patients Hospitalized to Coronary Care Units
Authors: Matsui Shigeru , Ishii Junichi , Okuyama Ryuunosuke , Takahashi Hiroshi , Kawai Hideki , Muramatsu Takashi , Yamada Akira , Motoyama Sadako , Naruse Hiroyuki , Hayashi Mutsuharu , Izawa Hideki , Ozaki Yukio
Published: July 2021

Background:
Acute kidney injury (AKI) detected after admission to coronary care unit (CCU) is associated with very poor outcomes. We prospectively investigated the prognostic value of a combination of AKI and high plasma D-dimer levels for 1-year mortality in patients hospitalized to CCUs.

Methods:
D-dimer, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and high-sensitive C-reactive protein (hsCRP) levels were measured in 1228 patients on admission to CCUs, of whom 56% had decompensated heart failure and 38% had acute coronary syndrome. AKI was defined as an increase of >25% in creatinine from baseline or an absolute increase of ≥0.5 mg/dL within 48 h after admission. Left ventricular ejection fraction (LVEF) and E/e’ ratio were estimated using echocardiography with tissue Doppler imaging.

Results:
AKI was detected in 163 (13%) patients. During 1-year follow-up period, there were 149 (12%) deaths. The patients who died were older (median: 77 vs. 73 years; p < 0.0001) and exhibited higher D-dimer (2.7 vs. 1.3 μg/mL; p < 0.0001), NT-proBNP (5495 vs. 1525 pg/mL; p < 0.0001), and hsCRP levels (0.92 vs, 0.26 mg/L; p < 0.0001) and E/e’ ratio (15.0 vs. 13.2; p = 0.006). They also had a higher incidence of AKI (26% vs. 12%; p < 0.0001) and lower LVEF (39% vs. 49%; p < 0.0001) and estimated glomerular filtration rate (45 vs. 62 mL/min/1.73 m
2
; p < 0.0001) than patients who survived. Multivariate Cox regression analysis, including 12 clinical, biochemical, and echocardiographic variables, identified AKI (relative risk: 1.79; p = 0.008) and increased D-dimer level (relative risk: 1.83 per 10-fold increment; p = 0.002) as independent predictors of 1-yeart mortality. The combined assessment of AKI and D-dimer quartiles was significantly associated with 1-year mortality rates (Figure).

Conclusions:
The combined assessment of AKI and high D-dimer levels may be useful for evaluating the risk of 1-year mortality in patients admitted to CCUs.