bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 16884: Involvement of Hydrogen Sulfide (H2S) in Dexamethasone (DEX) Induced Hypertension in Rat
Authors: Donnarumma Erminia , Mitidieri Emma , Tramontano Teresa , Brancaleone Vincenzo , Bucci Mariarosaria , d’Emmanuele di Villa Bianca Roberta , Sorrentino Raffaella
Published: July 2021

Introduction:
Glucocorticoid (GC) excess is related to hypertension. The deletion of endothelial GC-receptors abrogates the blood pressure increase, suggesting GC-induced hypertension is endothelium-dependent. In response to shear stress endothelium releases nitric oxide, endothelial derived hyperpolarizing factor (EDHF) and prostacyclin. Recently H2S has been proposed as a candidate for EDHF. H2S is mainly produced by the enzymes cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE) from L-cysteine. The aim of this study was to investigate the EDHF/H2S signaling in GC-hypertension.

Methods:
Male Wistar rats were treated with DEX (1.5 mg/kg/sc) or vehicle (VEH) for 8 days. Systolic blood pressure (SBP) was monitored every 2 days. EDHF was evaluated in mesenteric plexus and carotid artery performing a concentration-effect curve of acetylcholine in presence of indomethacin (INDO) and nitro-L-arginine methyl ester (L-NAME). Apamin (APA) plus charibdotoxin (CTX), SKCa and BKCa inhibitors, or propargylglycine (PAG), CSE inhibitor, were used. CBS and CSE levels were analyzed by immunoblot. H2S levels were measured by a colorimetric assay.

Results:
DEX treatment significantly increased SBP compared to VEH (*p<0.05, **p<0.01, ***p<0.001 at days 2-4, 6, 8 respectively). EDHF-mediated relaxation of mesenteric bed or carotid artery was markedly reduced in DEX group compared to VEH (***p<0.001). APA and CTX as well as PAG abolished EDHF-mediated relaxation in DEX or VEH group (***,°°°p<0.001 respectively). CBS and CSE levels were significantly reduced in mesenteric plexus and carotid artery in DEX group (*p<0.05). The H2S production was markedly reduced in mesenteric plexus and carotid artery (*p<0.05, **p<0.01 respectively) as well as plasmatic H2S levels (*p<0.05) in DEX rats compared to VEH.

Conclusions:
Our data demonstrate that GC-excess induces an impairment of H2S/EDHF signaling indicating an additional cause of GC-mediated hypertension.
Abstract 16983: Inhibition of Dynamin-Related Protein 1 Accelerates Vascular Calcification in apoE-Deficient Mice through AKT Activation
Authors: Rogers Maximillian , Maldonado Natalia , Fiats Tyler , Goettsch Claudia , Hutcheson Joshua D , Yamada Iwao , Aikawa Masanori , Aikawa Elena
Published: July 2021

Background:
Mitochondrial dysfunction has been implicated in the pathogenesis of cardiovascular disease. Dynamin-related protein 1 (DRP1) regulates mitochondrial function by driving membrane fission and allowing mitochondria to divide. How DRP1 acts in atherosclerosis, including the development of vascular calcification however remains unknown.

Methods and Results:
Aortic smooth muscle mitochondria from apoE-deficient mice (apoE-/-) exhibited a 47% increase in size compared to mitochondria from wild-type mice fed the same atherogenic diet for 18 weeks (N=103-129 mitochondria from 3 mice/group; p<0.05). In agreement with the observed changes in mitochondrial morphology, inhibitory phosphorylation of DRP1 on Ser637 was enriched in apoE-/- mouse aortas. DRP1 immunoreactivity increased around calcified areas of apoE-/- mouse aortic sections. Additionally, DRP1 mRNA was increased 1.8-fold in calcified over non-calcified areas (N=8; p<0.05). To determine the role of DRP1 inhibition on aortic lesion calcification, apoE-/- mice maintained on an atherogenic diet for 13 weeks (a point prior to calcified lesion development) were subsequently given the DRP1 inhibitor, MDIVI-1 (50mg/kg, i.p., once a week) for 5 more weeks. MDIVI-1 administration led to a 65% increase in calcified lesion area without altering lesion size (N=26 mice/group; p<0.05). A single injection of MDIVI-1 resulted in a 3-fold increase in the ratio of phospho-AKT to total pan-AKT along with a strong increase in Runx2 protein in the apoE-/- mouse aorta 6 hours post-injection. MDIVI-1 administration did not alter bone remolding as detected by micro-CT in wild type or apoE-/- mice (N=5 mice/group).

Conclusion:
We provide novel roles of the mitochondrial fission protein DRP1 in the vascular calcification process, and demonstrate that inhibition of DRP1 through administration of the DRP1 inhibitor MDIVI-1 in apoE-/- mice accelerates vascular calcification through the AKT/Runx2 pathway.
Abstract 17002: Performance of the Mortality Probability Model (MPM0) in a Contemporary Cardiac Intensive Care Unit
Authors: Rodrigo Maria E , Asch Federico M , Singh Tania A , Kumar Tishangi , Morrow David A , Chen Fang , Torguson Rebecca , Panza Julio A , Cooper Howard A
Published: July 2021

Introduction:
The Mortality Prediction Model (MPM0) was developed to estimate the probability of hospital mortality among patients in general and surgical intensive care units (ICUs).

Although this score is widely accepted, its applicability in patients with primary cardiac conditions has not been thoroughly evaluated. The aim of this study is to assess the performance of the MPM0 score in a cardiac intensive care unit (CICU).

Methods:
From 2007 to 2012, data related to variables from the MPM0 (Table 1) were prospectively collected on all consecutive patients admitted due to a primary cardiac condition to the CICU of a tertiary referral center. MPM0 was applied to all patients. Two variables of the original risk score were not included in the analysis: intracranial mass effect and cirrhosis. The incidence of each variable within the score was determined. Test performance was assessed using the area under the receiver operating characteristic curve (c-statistic).

Results:
A total of 6,433 patients were admitted to the CICU, of whom 5,710 (89%) had a primary cardiac diagnosis. Complete data were available for 4,641 patients, who comprise the study population. Primary cardiac diagnoses were: acute coronary syndrome (54%), arrhythmia (13%), valvular (12%), cardiomyopathy (8%), cardiac arrest (4%) and other (9%). Overall hospital mortality was 10.4%. The c-statistic for application of MPM0 to this population was 0.82 (95% CI 0.81-0.84), indicating excellent discriminatory capacity.

Conclusions:
The MPM0 risk score, described originally to aid in prediction of mortality for patients admitted to medical and surgical ICUs, performed extremely well when applied to cardiac patients admitted to a large contemporary CICU.
Abstract 17009: Clinical Characteristics and In-hospital Outcomes of Cardiac Transplant Recipients With Allograft Vasculopathy Undergoing Percutaneous Coronary Intervention: Insights from the National Cardiovascular Data Registry
Authors: Krim Selim R , Alkhouli Mohamad , Dasari Tarun W , Fonarow Gregg C , Saucedo Jorge F , Alvarez Rene , Ibrahim Homam , Dai David , Costa Marco , Wang Tracy Y , Lindenfeld JoAnn , Messenger John
Published: July 2021

Introduction:
Cardiac Allograft Vasculopathy (CAV) is a major limiting factor for long-term survival among cardiac transplant recipients. Large-scale data pertaining to the clinical characteristics and in-hospital outcomes in such patients undergoing Percutaneous Coronary Intervention (PCI) is lacking.

Methods:
We analyzed 1,897,328 patients from the NCDR CathPCI registry™ who underwent PCI of at least 1 native vessel between July 2009-December 2013 from 1477 centers, of which 542 patients (0.03%) had previous cardiac transplantation. After 4:1 propensity matching, clinical characteristics and in-hospital outcomes were compared between 538 cardiac transplant recipients and 2128 non-transplant patients.

Results:
Cardiac transplant recipients were more likely to have prior PCI, dyslipidemia, Canadian class 3/4 angina and were less likely to be smokers or present with ST segment-elevation myocardial infarction (0.9% vs. 7.1%, p<0.01) compared to the general population. Transplant recipients had fewer type C lesions (36% vs. 41% p=0.02) and were more likely to receive drug-eluting stents (DES: 81% vs. 76% p<0.01). In-hospital mortality, composite of death/MI/stroke, and bleeding complications were not significantly different between propensity-matched groups. (Table)

Conclusions:
Our large database analysis demonstrate that despite some differences in clinical characteristics, in-hospital outcomes among cardiac transplant recipients undergoing PCI for focal lesions associated with CAV were similar to the general population. Use of DES was higher in this group.
Abstract 17042: Surgery and Outcomes for Transposition of the Great Arteries among Developing World Congenital Heart Surgery Programs: a Report from the International Quality Improvement Collaborative
Authors: Schidlow David N , Jenkins Kathy J , Gauvreau Kimberlee , Croti Ulisses A , Giang Do Thi Cam , Sandoval Nestor F , Konda Rama K , Castaneda Aldo
Published: July 2021

Objectives:
Surgical care for CHD in the developing world is rapidly evolving, allowing an opportunity for survival for children with previously lethal conditions. Little information is available about such patients and their outcomes. The objectives of this study were to identify (1) patient characteristics, (2) surgical interventions, (3) institutional characteristics, and (4) risk factors for mortality among patients in the International Quality Improvement Collaborative (IQIC) undergoing surgery for transposition of the great arteries (TGA) with intact ventricular septum (IVS) and TGA with ventricular septal defect (VSD).

Methods:
We utilized a novel international collaborative database collected by developing world congenital heart surgical programs as part of a QI project. All TGA (IVS and VSD) cases from 2010-2012 were included. Demographic, surgical and institutional characteristics and their associations with in-hospital mortality were identified.

Results:
There were 559 patients at 21 centers who underwent surgery for TGA: 348 TGA/IVS and 211 TGA/VSD. TGA/IVS patients underwent arterial switch operation (ASO), 282 (81%); 2-stage ASO, 24 (7%); and atrial switch (ATS) 42, (12%). TGA/VSD patients underwent ASO, 169 (80%); 2-stage ASO, 19 (9%); and ATS, 23 (11%); all with VSD closure. In-hospital mortality ranged from 10% to 25% depending on procedure (Figure). Unadjusted mortality rates were higher among centers performing <10 TGA repairs yearly (OR 3.98; 95% CI 2.08-7.60, p<0.001). Among patients with TGA/IVS who underwent primary ASO, risk factors for mortality included male gender (p=0.05), weight <3 kg (p=0.04), and prematurity (p=0.007).

Conclusions:
Infants with TGA in the developing world increasingly have access to complex surgical repairs, and the majority of such patients undergo single-stage ASO. Mortality remains substantial; however, multi-center collaborative QI efforts are likely to benefit these patients.
Abstract 17048: Exosomes From Induced Pluripotent Stem Cells Deliver Cardioprotective Mirnas and Prevent Cardiomyocyte Apoptosis in the Ischemic Myocardium
Authors: Wang Yingjie , Zhang Lan , Weintraub Neal L , Tang Yaoliang
Published: July 2021

Induced pluripotent stem (iPS) cells exhibit enhanced survival and proliferation in ischemic myocardium and thus represent a promising source of cell-based therapy for myocardial ischemia-reperfusion (MIR) injury. However, the therapeutic application of iPS cells is limited by their tumorigenic potential. We hypothesized that iPS cells can transmit cytoprotective signals to cardiomyocytes via exosomes, nanovesicles that contain proteins, mRNAs and microRNAs (miRNAs) that can regulate cell function. Exosomes secreted from mouse cardiac fibroblast (CF)-derived iPS cells (iPS-exo) were purified from conditioned medium and confirmed by electron micrograph and protein expression of the exosome markers CD63 and Tsg101. We observed that iPS-exo are taken up by cultured H9C2 cardiomyocytes with high efficiency in time-dependent fashion. Uptake of iPS-exo protects H9C2 cells against H2O2-induced oxidative stress by inhibiting caspase 3/7 activation (P<0.05, n=6). To investigate whether iPS-exo treatment can protect against MIR injury, we injected exosomes secreted by CF (CF-exo), iPS-exo, or PBS (control) intramyocardially into mouse ischemic myocardium before reperfusion. After 24hs, TUNEL analysis showed that iPS-exo reduced cardiomyocyte apoptosis by about 66% in comparison with PBS control (p<0.05, n=6), and by about 50% in comparison with CF-iPS (P<0.05, n=6). Western blotting demonstrated that iPS-exo treatment significantly decreased the active caspase3 compared with PBS and CF-exo treatment (P<0.05, n=3). Furthermore, iPS-exo deliver cardioprotective miRNAs, including Nanog-regulated miR-21 and HIF-1α-regulated miR-210, to H9C2 cardiomyocytes in vitro. In conclusion, iPS-exo are biological nanoparticles carrying survival messages that can be efficiently transmitted to cardiomyocytes to protect against MIR.
Abstract 17071: Growth Asymmetry, Head Circumference and Neurodevelopmental Outcomes in Infants with Single Ventricles
Authors: Miller Thomas A , Zak Victor , Shrader Peter , Ravishankar Chitra , Pemberton Victoria L , Newburger Jane W , Shillingford Amanda J , Lambert Linda M , Sananes Renee , Richmond Marc E , Cnota James F , Hsu Daphne T , Miller Stephen G , Zyblewski Sinai C , Williams Richard V ,   Pediatric Heart Network Investigators
Published: July 2021

Poor somatic growth is common in infants with single ventricle (SV) physiology and has been linked to increased morbidity and impaired neurodevelopment. Asymmetry in somatic growth, a potential brain-sparing adaptation, is important in predicting outcomes in premature and small for gestational age (SGA) infants.

Objectives:
To assess variability in growth asymmetry and its associations with neurodevelopment in infants with SV.

Methods:
We analyzed growth asymmetry (weight for age z-score (WAZ) minus head circumference for age z-score (HCAZ)), relative head growth (change in cm/change in kg), HCAZ, and change in HCAZ from baseline to pre-Glenn in subjects prospectively enrolled in the Pediatric Heart Network Infant Single Ventricle (ISV) trial. Associations between these indices and results of the Psychomotor Developmental Index (PDI) and Mental Developmental Index (MDI) of the Bayley Scales of Infant Development-II (BSID) at 14 months were assessed.

Results:
Of the 230 patients enrolled in ISV, complete biometric data and BSID results were available in 168 (73%). For this cohort, age at enrollment was 21±9 days, age at pre-Glenn was 167±52 days, gestational age was 38.3±1.4 weeks, and 71% were male. Growth asymmetry varied across the cohort at enrollment (0.43 ±1.02, range -2.85 to 4.84) and the pre-Glenn visit (-0.23 ±1.21, range -4.45 to 3.00) as did the relative head growth (2.40±0.86, range 0.50 to 8.00). BSID scores were not associated with indices of growth asymmetry. In univariate analysis, larger pre-Glenn HCAZ correlated with higher MDI (r=0.21, p=0.006) and PDI (r=0.38, p<0.001) and greater increase in HCAZ from enrollment to pre-Glenn was associated with higher PDI (r=0.15, p=0.049). In multivariable modeling adjusting for site, serious adverse events, stage 1 length of stay, and height at 14 months, pre-Glenn HCAZ was an independent predictor of PDI (p=0.03), but not MDI. For each one unit Z-score increase in pre-Glenn HCAZ, the predicted PDI score increased by 2.5 points.

Conclusions:
In infants with SV, BSID scores were associated with pre-Glenn HCAZ but not with the degree of asymmetric growth. Future studies should explore why asymmetric growth that seems important in premature and SGA infants appears less relevant in infants with SV.
Abstract 17075: Outcomes in Radiation Associated Cardiac Disease Patients that present with Coronary Artery Disease: Comparison between PCI and CABG
Authors: Masri Ahmad , Grant Reed , Ellis Stephen , Smedira Nicholas G , Lytle Bruce W , Griffin Brian P , Desai Milind Y
Published: July 2021

Background:
Radiation associated cardiac disease (RACD) patients have a characteristic presentation, including aggressive coronary artery disease (CAD), observed years after index radiation for thoracic malignancy; & portends a worse prognosis, as compared to matched controls. In patients with prior thoracic radiation & obstructive CAD, we sought to compare outcomes between those undergoing percutaneous coronary intervention (PCI) vs. coronary artery bypass grafting (CABG).

Methods:
We studied 267 consecutive patients with prior thoracic malignancy (including 58% breast & 20% Hodgkin’s) & thoracic radiation (25 % to right breast, 30% to left breast, 45% to mediastinum) who presented for treatment of RACD manifesting as advanced CAD (138 for PCI & 129 for CABG) between 1994-2013 (excluding those with known CAD prior to radiation or concomitant valvular disease). Clinical, angiographic & echo data were recorded. Mortality was recorded (including due to recurrent malignancy).

Results:
Clinical data of 2 groups are shown in the Table. At 9±5 years of follow-up, there were 58 (22%) deaths (17 due to recurrent malignancy). On stepwise multivariable Cox Proportional Hazard Analysis, Euroscore (Hazard ratio [HR] 1.28 [1.13-1.45], p<0.001 was the only significant predictor of cardiac deaths. There was no difference in cardiac deaths between PCI vs. CABG (HR 1.40 [0.73-2.70], p=0.3).A higher % of patients with known recurrent malignancy underwent PCI as opposed to CABG; & died during follow-up (11% vs 2%, p<0.001).Higher % of patients in the PCI group had a repeat PCI during follow-up, vs. CABG group (11% vs. 5% p<0.05).

Conclusion:
Patients with prior thoracic radiation & suspected RACD, the majority of whom are females, have a varied presentation for CAD (including a high % with proximal disease). Long-term survival from cardiac death is similar in PCI vs. CABG groups. RACD patients that have recurrent malignancy tend to have more PCI than CABG for relief of symptomatic CAD.
Abstract 17098: Comparison of Angiographic and 1-year Clinical Outcomes between Long Single Stent and Overlapping Double Stent in Patients with Newer Generation Drug-Eluting Stents for Similar Long Lesions
Authors: Mori Naoki , Nishino Masami , Okamoto Naotaka , Tanaka Akihiro , Yoshimura Takahiro , Makino Nobuhiko , Egami Yasuyuki , Shutta Ryu , Tanouchi Jun
Published: July 2021

Background:
Although overlapping coronary stents in long lesions by percutaneous coronary intervention are common, some clinical studies revealed adverse clinical and angiographic outcomes of early generation overlapping drug-eluting stents (DES) due to increased drug and polymer toxicity, as compared to non-overlapping or single DES. However, recent clinical reports have shown safety and efficacy outcomes of overlapping newer generation DES, as compared with early generation overlapping DES and newer generation non-overlapping DES. Thus, the purpose of this study was to compare angiographic and 1-year clinical outcomes between long single stent and overlapping double stent in patients treated with newer generation DES for similar long lesions.

Methods:
We analyzed 8-10 months angiographic and 1-year clinical outcomes of 106 patients treated with everolimus-eluting stent (EES, newer generation DES) in a de novo similar long lesions (≥ 32mm, ≤38mm) by a long single stent or overlapping double stents. We divided our patients into single long stent group and overlapping double stent group. We compared the incidence of in-stent restenosis (ISR), which was defined as more than 50% angiographical stenosis, and analyzed freedom from major adverse cardiovascular events (MACE: defined as the composite of death, myocardial infarction, or target vessel revascularization) and freedom from target lesion revascularization (TLR) at 1 year using Kaplan-Meier method.

Results:
The incidence of ISR at 8-10 months after stent implantation was similar between long single stent group (n=41) and overlapping double stent group (n= 65). The rate of freedom from MACE and TLR during 1-year were also similar between two groups (figures).

Conclusions:
According to our study, newer generation DES, EES, provided similar angiographic and 1-year clinical outcomes irrespective of overlap status in long lesions.
Abstract 17100: Priming with Erythropoietin Enhances Survival and Pro-Angiogenic Properties in Mesenchymal Stem Cells
Authors: Mizukami Takuya , Iso Yoshitaka , Usui Haruka , Sato Chisato , Sasai Masahiro , Shioda Seiji , Suzuki Hiroshi
Published: July 2021

Introduction:
Accumulating evidence from animal studies shows that the administration of mesenchymal stem cells (MSCs) from bone marrow ameliorates tissue damage after ischemic injury. However, the inability to effectively graft culture-expanded stem cells to diseased or injured tissues remains a challenge for cell therapy. Erythropoietin (Epo) is an erythropoiesis-stimulating cytokine and protects erythroid progenitors from cell death. Epo receptor was identified in MSCs, but the action of Epo/Epo receptor signaling is not determined. In the present study we investigated whether Epo enhanced the survival and pro-angiogenic potential in the MCSs in both culture and animal experiments.

Methods and Results:
Epo receptor was expressed on MSCs isolated from bone marrow in GFP-transgenic rats. In culture study, the Epo treatment (80IU/ml) significantly propagated the MSCs compared with the controls (2-fold increase, p<0.05). Quantitative RT-PCR analysis demonstrated that Epo significantly enhanced the expressions of basic-fibroblast growth factor and stromal cell-derived factor-1 in the cultured MSCs. In vivo, the GFP-MSCs preconditioned with and without Epo (80IU/ml) for 48 hours were locally administered to rat hindlimb ischemia model (n=11 in each group). Priming with Epo significantly increased the MSC engraftment in perivascular area of the injured muscle at day 3 after the implantation more than without Epo (1.5±1.3 vs. 3.0±2.1, p<0.05). The MSCs preconditioned with Epo significantly promoted blood perfusion documented by laser Doppler and capillary growth in histological study compared with the control group at day 14 (p<0.05, respectively). In addition to promoting neovascularization, the MSCs with Epo significantly inhibited macrophage infiltration in perivascular are (p<0.05 vs. the control).

Conclusions:
Epo induced the proliferative activity and enhanced the production of angiogenic cytokines in the cultured MSCs from bone marrow. In vivo study demonstrated that the short-term priming with Epo promoted the cellular engraftment and neovascularization in the MSC therapy for ischemic limb muscle. MSC implantation combined with Epo may be a novel and feasible strategy in therapeutic angiogeneis.
Abstract 17101: Low-intensity Anticoagulant Treatment in Chinese Patients with Mechanical Heart Valve Prostheses: Early Outcomes of a Prospective, Multicenter Registry in China
Authors: HU JIA , FU BO , Xu Jian-ping , Shi Ying-kang , Dong Li
Published: July 2021

Background:
Current guidelines recommend vitamin K antagonist treatment with relatively higher international normalized ratio (INR) targets for patients with mechanical heart valve prostheses. However, there is lack of data from large clinical trials about the outcomes of low-intensity anticoagulant treatment in Chinese patients with mechanical heart valves.

Methods:
The Low-intensity Anticoagulation Therapy after Heart Valve Replacement is an ongoing multicenter, prospective, observational cohort study (ChiCTR-OCH-10001185). Between January 2011 and August 2013, qualified patients from 34 cardiac centers in China mainland were recruited in the Anticoagulation Therapy Database of Chinese Patients after Heart Valve Replacement. Baseline characteristics were collected and patients were followed up for anticoagulant treatment, INRs and adverse events till March 2014.

Results:
The database recruited 11,769 patients, and 11,040 patients (93.8%) undergoing mechanical heart valve replacement were analyzed in this study. The mean age was 48.9±11.5 years and 6,227 patients (56.4%) were female. A total of 9,870 patients (89.4%) of the baseline population completed at least 6 months follow-up. The median follow-up time was 1.2 years (range 0.5-2.2). For all 9,870 patients, 143,115 measurements of the INR were obtained. The average warfarin dosage was 2.98±1.16mg/d and the mean INR was 1.81±0.46, and 88.7% patients had an INR level≤2.5 during the follow-up period. The incidence of hemorrhagic events was the lowest in patients with an INR≤2.0, whereas the risk of thromboembolic complications in this group of patients was not significantly increased (Table 1).

Conclusions:
Low-intensity anticoagulation with an INR of 1.5 to 2.5 is safe and effective for Chinese patients with mechanical heart valves in short-term. The optimal INR targets for mechanical valve recipients with different implanting positions and risk factors require further investigation.
Abstract 17128: Pathophysiology of Coronary Artery Disease in Hiv-infected Patients: Dissociation Between Anatomy and Function
Authors: Mancone Massimo , Cinque Alessandra , Bruno Noemi , Armato Alessandra , Salvi Nicolò , Ceccacci Andrea , Bruno Pasqualina , Sardella Gennaro , d’Ettorre Gabriella , Vullo Vincenzo , Fedele Francesco
Published: July 2021

Introduction:
Numerous reports suggest, among HIV+ patients (pts), an increased rate of acute coronary syndrome and cardiac death. Several data suggest that endothelial dysfunction is a major mechanisms in the development of coronary atherosclerosis in non-HIV infected patients.

Hypothesis:
The aim of our study is to assess coronary microvascular function using Doppler-flow wire in HIV+ patients in therapy with HAART.

Methods:
Thirteen HIV-infected patients were enrolled from the Department of Cardiovascular, Respiratory, Nephrology, Anesthesiology and Geriatric Sciences of the “Sapienza” University of Rome (Italy).

The main inclusion criteria were: Framingham risk score <10%, absence of metabolic syndrome (according to the definition of Adult Treatment Panel III e ATPIII12), negative echocardiographic and ECG stress-test and negative for anti-HCV antibodies.

Diagnostic coronary angiography was performed via percutaneous radial approach. Microvascular function was assessed by measuring coronary flow velocity reserve (CFR). Intracoronary functional tests were performed to evaluate both endothelium-dependent microvascular function [via intracoronary (IC) infusion of acetylcholine (2.5[[Unable to Display Character: –]]10 μg)] and non-endothelium-dependent microvascular function [via IC infusion of adenosine (5 μg) ].

Results:
All the patients presented a Framingham risk score <10%. The medium age was 53.3±4.1 years. The mean duration of highly active antiretroviral therapy was 12.9±2.4 years. Thirteen patients presented 23 coronary atherosclerotic plaques; while endothelium and non endothelium-dependent microvascular function was quite normal in our population (CFR after adenosine 2.37±0.4; CFR after Achetylcholine 2.43±0.4).

Conclusion:
Microvascular function is not compromised in HIV + pts who presented coronary atherosclerotic plaque. Microvascular dysfunction, involved in pathophysiology of coronary artery disease in general population, seems to be not implicated in coronary atherosclerosis in HIV + pts. These data suggest a peculiar pathophysiological mechanisms for HIV related atherosclerosis.
Abstract 17185: Hemodynamic Variables and Vasopressor Support After Out-of-hospital Cardiac Arrest: Associations With 1-year Neurologic Outcome
Authors: Laurikkala Johanna , Wilkman Erika , Varpula Tero , Reinikainen Matti , Hoppu Sanna , Ala-Kokko Tero , Tallgren Minna , Ruokonen Esko , Tiainen Marjaana , Pettilä Ville , Vaahersalo Jukka , Skrifvars Markus ,   Finnresusci Investigators
Published: July 2021

Introduction:
Optimal blood pressure target in resuscitated patients is unknown but current guidelines recommend maintaining mean arterial pressure (MAP) between 60 to 90 mmHg. Our aim was to determine associations between time-weighted MAP levels and vasopressor load (VL) during the first 48 hours after OHCA and 1-year neurologic outcome in a prospective observational cohort of OHCA patients treated in the ICU.

Methods:
We included 503 patients with out-of-hospital-cardiac arrest (OHCA) treated in 21 ICUs from the FINNRESUSCI study between 2010 and 2011. Hemodynamic data and vasopressor doses were collected prospectively in two, five or 15 minute intervals depending on the ICU. Totally 1.2 million blood pressure values were analysed. We identified optimal thresholds for time-weighted (TW) MAP and outcome with receiver operating characteristic curve analysis (ROC). Using multivariate regression including co-morbidities, factors at resuscitation, sequential organ failure scores, TW MAP and total VL, we tested associations with 1-year neurologic outcome, dichotomized to good (CPC 1-2) and poor (CPC 3-5), respectively.

Results:
Of 503 patients, 202 (40 %) patients had a good and 301 (60 %) patients had poor 1-year outcome. Receiver operating characteristic analysis regarding poor one year outcome was performed for different MAP areas: hypotension areas under 65 mmHg (AUC 0.607, 95% CI 0.558 - 0.656, P-value < 0.001) and under 70 mmHg (AUC 0.605, 95% CI 0.555 - 0.654, P- value < 0.001). The mean vasopressor load was higher in patients with good 1-year outcome than in those with poor outcome (p-value < 0.001). With multivariate regression analysis neither TWA MAP below 70mmHg (OR 1.0, 95% CI 0.999 - 1.001, p-value 0.909) nor vasopressor load (OR 1.004, 95% CI 0.994 - 1.013, p-value 0.52) were independent predictors of long-term outcome.

Conclusions:
In this large prospective study of OHCA patients, we found no associations between MAP values during the first 48h and long-term outcome. Contrary to previous expectations, higher MAP values had no neuroprotective effect. Neither did vasopressor load associate with outcome.
Abstract 17193: Porcine Xenograft for Aortic-, Mitral- and Double Valve Replacement. Longterm Results
Authors: Lehmann Sven , Merk Denis , Oberbach Andreas , Etz Christian , Seeburger Joerg , Garbade Jens , Leontyev Sergey , Misfeld Martin , Mohr Friedrich W
Published: July 2021

Introduction:
Aim of this study was to evaluate the results after stented porcine xenograft implantation (EpicTM, SJM, St.Paul, MN, USA) with Linx™ anticalcification treatment in elderly patients.

Methods:
A total of 2544 patients receiving aortic (AVR = 1920), mitral (MVR = 347) or double valve (DVR = 277) replacement between 11/2001 and 03/2012 were evaluated. All Patients having elective or emergency indications were included. Outcome was assessed by reviewing the prospectively acquired hospital database results as well as regular follow-up information by annual written interview.

Results:
Patient age was 76.5±6 (AVR), 73.8±7 (MVR) and 74.2±7 (DVR) years; 54.2% / 41.9% / 42.0% were male, active endocarditis was in 4.5% / 19.9% / 22.1% indication for valve surgery and the logistic EUROSCORE predicted risk for mortality was 15.4±15% / 19.9±19% / 22.3±21%, respectively. Additional surgical procedures were mitral valve repair in 196 (10.2%) (AVR) patients, CABG in 840 [43.8%] (AVR), 82 [23.7] (MVR) and 94 [34.1%] (DVR) patients, cryoablation in 232 [12.1%] / 81 [23.4%] / 67 [24.3%] patients, and surgery on the thoracic aorta in 166 [8.7%] / 12 [3.5%] / 41 [14.9%] patients. Mean aortic cross clamp time was 72.6±28min / 79.9±41min / 125.3±44min. Mean follow-up was 4.2±3.3 years. Freedom from endocarditis after 9 year was 98.3±0.4% / 97.5±1.0% / 97.4±1.6% (p=n.s.). Freedom for valve reoperation was 96.3±0.6% / 93.8±2.4% / 92.8±2.2% (AVR vs. DVR p=0.009). Freedom from neurological event was 95.4±0.9 / 91.5±2.9 / 97.9±1.3. 30 day survival was 89.1±0.07% / 80.4±.2.1% / 77.5±2.5% and 9 year survival was 44.0±1.3% / 33.9±4.7% / 29.5±4.1%, respectively.

Conclusions:
EpicTM stented porcine xenograft is associated with acceptable survival, freedom from valve related complication and freedom from valve reintervention.
Abstract 17216: Intracoronary Dual-modal OCT/NIRF Structural-Molecular Imaging with a Clinical Dose of Indocyanine Green (ICG) for Detection of High-risk Coronary Plaques in Diabetic Swine Model
Authors: Kim Sunwon , Lee Min Woo , Cho Han Saem , Song Joon Woo , Lee Sunki , Oh Dong Joo , Park Kyeongsoon , Oh Wang-Yuhl , Yoo Hongki , Kim Jin Won
Published: July 2021

Background:
Acute coronary syndrome is frequently caused by rupture of macrophage abundant plaques with a large lipid-rich core. The present study aimed to investigate whether a fully integrated OCT/NIRF imaging combined with a clinically available near-infrared fluorescence (NIRF) enhancing ICG can detect the inflamed, lipid-rich plaques in swine coronary atheromata whose phenotype is similar to human vulnerable fibroatheroma.

Methods and Results:
Accelerated atherosclerosis was made by coronary balloon denudation in alloxan induced diabetic minipigs. A rapid coronary imaging (20 mm/sec pullback speed) using a fully integrated OCT/NIRF catheter was safely performed 30 minutes after I.V. injection of ICG (2.0 mg/kg) just under contrast purge. OCT clearly identified the lipid-rich plaques with fibrous cap. Simultaneously acquired, distance-calibrated NIRF imaging detected lipid-laden macrophage signals in OCT-proven plaques (figure). The
in vivo
plaque target-to-background ratio (pTBR) was significantly higher in ICG-injected swine compared to non-diabetic swines or saline-injected controls (p<0.05), which was validated on
ex vivo
fluorescence reflectance imaging (FRI) (figure). The
in vivo
and
ex vivo
peak pTBRs correlated significantly (p<0.05).
In vitro
experiments, and histopathology including fluorescence microscopic imaging and immunostaining of the plaque sections corroborated the findings
in vivo
.

Conlusions:
An OCT/NIRF imaging with a clinical use of ICG accurately identified macrophage abundant, lipid-rich coronary plaques in diabetic atheromatous minipigs. This highly translatable dual-modal molecular-structural imaging could be relevant for clinical intracoronary detection of high-risk plaques.
Abstract 17225: Extracellular Signal-Regulated Kinase 1/2 is Essential for Lipocalin-2 Signaling in Endothelial Cells
Authors: Theurl Markus , Schroll Andrea , Theurl Igor , Lener Daniela , Franz Wolfgang-Michael , Weiss Guenter , Kirchmair Rudolf
Published: July 2021

Introduction:
Lipocalin-2 (Lcn2) is an acute phase protein and a marker of kidney injury. Recently, elevated Lcn2-levels have been reported in heart failure and myocardial infarction. Moreover, stimulation of breast cancer angiogenesis was observed. Thus, we hypothesized that Lcn2 may be a regulator of vascular function and a target for the treatment of ischemic vascular disorders.

Methods/Results:
In-vitro Lcn2 mediated proliferation of human umbilical vein endothelial cells (HUVEC; rel. proliferation Lcn2 10 nM vs. ctr.: 1.4±0.09, n=3, P<0.001) and human coronary artery endothelial cells (HCAEC; rel. proliferation Lcn2 10 nM vs. ctr.: 1.3±0.07, n=3, P<0.01) as determined by BrdU-incorporation. In the in-vitro matrigel assay stimulation of HUVEC (1.4 fold vs. ctr., n=3, P<0.01) and HCAEC (1.6 fold vs. ctr., n=3, P<0.001) with Lcn2 resulted in a significant induction of capillary like tube formation. All effects were similar to vascular endothelial growth factor (VEGF). Mechanistically these results can be traced back to phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2). Real-time PCR analyses revealed expression of Lcn2 and its receptor by endothelial cells (EC) as well as a hypoxia-dependent up-regulation (rel. Lcn2 mRNA hypoxia vs. normoxia 1.6±0.2, P<0.05; rel. Lcn2-receptor mRNA hypoxia vs. normoxia 2.6±0.2, P<0.001).

In the mouse aortic ring assay Lcn2-treatment resulted in a significant outgrowth of EC similar to VEGF. In the hind limb ischemia (HLI) model Lcn2 -/- mice showed an impressive phenotype. After induction of HLI we detected significantly more tissue defects compared to wild type (WT) mice. The ischemia-related lesions were more severe as determined by necrosis score (necrosis score Lcn2 -/- 1.8±0.2 vs. WT 0.7±0.2, n=5, P<0.01) and amputation rate was significantly higher. In ischemic hind limbs of Lcn2 -/- mice ERK1/2-phosphorylation was almost abrogated which might be an underlying mechanism. Transplantation of WT-bone marrow to irradiated Lcn2 -/- mice didn’t influence the outcome suggesting that observed effects are rather endothelium-dependent than influenced by an inflammatory response.

Conclusion:
Lcn2 might be a promising therapeutic factor for the treatment of ischemic vascular disorders.
Abstract 17261: Inhibition of Fibrinolysis Attenuates Influenza A-induced Lung Injury
Authors: Morales-Nebreda Luisa , Eren Mesut , Soberanes Saul , Nigdelioglu Recep , Rogel Micah , Chi Monica , Cho Takugo , Hamanaka Robert , Vaughan Douglas E , Budinger GR Scott , Mutlu Gokhan M
Published: July 2021

Rationale: Influenza A virus (IAV) is the leading cause of death from an infectious cause and ranks 8th in the list of attributable annual mortality in the United States. Currently available antiviral treatments are limited and may become ineffective as resistant strains emerge. The coexistence of hemostatic alterations with inflammatory responses to viral infections support the idea that common molecular mechanisms contribute to the regulation of these systems. Previous studies demonstrated that IAV induces the activation of both coagulation and fibrinolytic pathways, and that the impairment of the latter is mainly attributable to high levels of plasminogen activator inhibitor type I (PAI-1), the major inhibitor of tissue-type plasminogen activator (t-PA). Interferon-α (IFN-α) plays a key role in the control of viral replication and overall shaping of the immune response. We sought to determine whether PAI-1, plays a role in the immune response and morbidity and mortality associated with IAV infection.

Methods:
Wild-type (C57BL/6J), PAI-1-/-, t-PA-/- and PAI-1 stab (transgenic mice expressing an active form of human PAI-1) mice were treated intratracheally with IAV (A/WSN/33 [H1N1] 500 pfu/mouse in 50μl PBS). We assessed the levels of IFN-α in bronchoalveolar lavage fluid (BALF) on day 2 and 4, and influenza A-induced morbidity (weight loss) and mortality.

Results:
Compared with wild-type mice, PAI-1-/- mice had increased IAV-induced morbidity and mortality. In contrast, both PAI-1 stab and t-PA-/- mice had improved survival. In wild-type mice, IAV induced a significant elevation IFN-α levels in BALF. PAI-1 stab mice had a 2-fold increase, while PAI-1-/-mice had a 69% reduction in IFN-α levels in BALF compared to wild-type mice.

Conclusions:
Inhibition of fibrinolysis by means of genetic overexpression of PAI-1 or deletion of t-PA augments the antiviral response and attenuates the morbidity and mortality associated with IAV infection. These results suggest an important functional role for PAI-1 and fibrinolysis in the pathogenesis of influenza A infection. Modulation of the fibrinolytic pathway or PAI-1 may potentially be useful as a target for novel therapeutics in the management of IAV-induced lung injury.
Abstract 17268: Echocardiographic Predictors of Cardiopulmonary Exercise Test Performance in Hypertrophic Cardiomyopathy
Authors: Larsen Carolyn M , Ball Caroline A , Hebl Virginia B , Geske Jeffrey B , Ong Kevin C , Siontis Konstantinos C , Olson Thomas P , Allison Thomas G , Ommen Steve R
Published: July 2021

Introduction:
Patients with hypertrophic cardiomyopathy (HCM) have lower peak oxygen uptake (VO2) than healthy peers. The mechanism of peak VO2 limitation in HCM has not been fully elucidated.

Hypothesis:
We assessed the hypothesis that resting echocardiographic parameters are predictive of peak VO2 in HCM.

Methods:
A retrospective review of adult HCM patients seen at a tertiary referral center from 2006-2012 was performed. Patients who underwent a comprehensive echocardiogram and cardiopulmonary treadmill exercise test within 1 week were included. Multivariate modeling was used to identify predictors of peak VO2 adjusting for age, sex, body mass index, beta blocker use, diabetes, smoking, systolic blood pressure, and obstructive HCM.

Results:
Five hundred and forty one patients met the inclusion criteria. The average age was 52 +/- 0.65 years, 62% were male, 78% had obstructive HCM, and 42% were NYHA class III or IV. Independent predictors of peak VO2 included averaged left ventricular (LV) longitudinal peak systolic strain (p<0.01) and right ventricular systolic pressure (RVSP) (p<0.01) (Figure 1). Obstructive versus non-obstructive HCM, grade of diastolic dysfunction, LV mass and wall thickness, left atrial volume index, right ventricular dysfunction and moderate or greater mitral or tricuspid regurgitation were not independent predictors of peak VO2.

Conclusions:
In conclusion, higher RVSP and less negative LV longitudinal peak systolic strain were moderate independent predictors of lower peak VO2. These findings confirm the hypothesis that resting echocardiographic parameters are predictive of peak VO2 in HCM. Further study of the relationship between echocardiographic findings and outcomes on cardiopulmonary exercise testing may help elucidate the mechanisms of exercise limitation in HCM.
Abstract 17295: Cardiovascular Biomarkers and Long-term Outcomes in Patients with Type 2 Diabetes Mellitus Treated with Alogiptin vs. Placebo in the EXAMINE Trial
Authors: Morrow David A , Cannon Christopher P , Zannad Faiz , Cushman William C , Bakris George L , Nissen Steven E , Heller Simon R , Bergenstal Richard M , Perez Alfonso T , Fleck Penny R , Mehta Cyrus R , Kupfer Stuart , Lam Hung , Wilson Craig , White William B
Published: July 2021

BACKGROUND:
Thorough evaluation of the cardiovascular (CV) safety of new drugs for diabetes mellitus (DM) is now mandated by the US FDA. Alogliptin, a dipeptidyl-peptidase 4 inhibitor, is one of a new drug class for treatment of DM. CV biomarkers may provide useful insight with respect to CV safety of new treatments for DM. We evaluated the predictive value of baseline biomarkers for CV outcomes in a high risk population of DM patients (pts) in a large CV safety trial.

METHODS:
EXAMINE was a randomized, double-blind, placebo-controlled, multinational trial of alogliptin in pts with DM enrolled 15 to 90 days after an acute coronary syndrome (ACS). We measured B-type natriuretic peptide (BNP) and high sensitivity troponin I (hsTnI) at baseline (Abbott ARCHITECT). The primary endpoint was major adverse CV events (MACE) defined as CV death (CVD), myocardial infarction, or stroke. The composite of CV death or heart failure (HF) was also assessed as an exploratory endpoint.

RESULTS:
A total of 5230 pts with baseline biomarkers were followed for 18 mo (median). Baseline BNP and hsTnI showed a significant graded relationship with CV outcomes at 18 mo (Figure bars). BNP and hsTnI remained strongly and independently related to CV outcomes through the pts’ final visit after adjusting for age, sex, type of qualifying ACS, eGFR, & history of HF (Figure, adjusted HRs). The rates of MACE were similar with alogliptin vs. placebo in the highest risk pts identified by BNP (Group 4: 19.9 vs. 22.2%) or hsTnI (Group 4: 18.3 vs. 20.6%). Similar results were observed for CV death/HF based on BNP (17.5 vs. 19.4%) or hsTnI (14.3 vs. 14.9%). There was no evidence for heterogeneity in the effect of alogliptin on CV death/HF across BNP strata (p-interaction=0.71).

CONCLUSIONS:
Among pts with DM who were stable after a recent ACS, BNP & hsTnI identified pts at high risk of poor CV outcomes. In this study, the rates of MACE, including CV death or HF, were not increased with alogliptin vs. placebo even in these high risk pts.
Abstract 173: The Effectiveness of Continuous Voice Feedback in Telephone CPR to Maintain the Quality of Hands-Only Cardiopulmonary Resuscitation
Authors: Hara Takahiro , Tanaka Hideharu , Takahashi Hiroyuki , Kinoshi Tomoya , Shirakawa Toru , Gotoh Soh , Hasegawa Eiichi
Published: July 2021

Background:
Also, it is well known that telephone-CPR (T-CPR) is effective to increase the rate of bystander CPR. However few reported suggested that T-CPR’ effective trough neurologically favorable outcome due to lack of adequate feedback.

Purpose:
The aim is this study is to identify the effective voice feedback during on T-CPR.

Method:
Twenty layperson without CPR training experience for at least 1 year were enrolled. They performed Hands-only CPR for 4 minutes followed by in 3 ways randomly. The first way is no feedback in the trial (non-FB Group). Second, they receive feedback in each 30 seconds (30sec-FB group). The third, they receive feedback in each 10 seconds (10sec-FB group) with enough interval time(30min) to restoration by fatigue, respectively. The feedback is simply telling by phone laypersons to push harder no matter how their compressions. Paired t-test were applied for statically analysis.

Result:
The average depth of 4 minutes through is 40.9±8.3mm with non-FB group, 43.8±6.5mm with 30sec-FB group, 47.8±5.9mm with 10sec-FB group, respectively. Statically significance were seen in non-FB groups and 30 sec-FB groups(P<.05) compared with 10sec-FB group. The compression depth decreasing by time in each group, however the decrease rate is higher in non-FB group than 10sec-FB group and 30sec-FB group(P<.05), respectively.

Discussion:
Chest compression depth in layperson is normally not enough. But the depth increased when they positive voice feedback. However they could keep better compressing for entire 2 minutes.

Conclusion:
The continuous feedback by phone is necessary to make layperson to perform quality chest compression. Further investigation warrant.
Abstract 17302: A Meta-Analysis of Major Adverse Cardiovascular and Cerebrovascular Events in Patients Undergoing Transcatheter Aortic Valve Implantation Using Edwards SAPIEN valve versus Medtronic CoreValve for Severe Aortic Stenosis
Authors: Panchal Hemang B , Barry Neil , Bhatheja Samit , Albalbissi Kais , Paul Timir
Published: July 2021

Background:
In patients with severe aortic stenosis (AS) who are at high risk for surgery, a transcatheter aortic valve implantation (TAVI) is an emerged alternative procedure using Edwards SAPIEN valve (EV) or Medtronic CoreValve (CV). The purpose of this meta-analysis is to compare early major adverse cardiovascular and cerebrovascular events (MACCE) between EV and CV.

Methods:
PubMed and the Cochrane Center Register of Controlled Trials were searched through May 2014. Seventeen studies (n=6211) comparing TAVI procedure that used EV (n=2693) and CV (n=3518) were included. End points were post-procedural all-cause mortality, cardiovascular mortality, myocardial infarction, stroke, major bleeding and major vascular events. The odds ratio (OR) with 95% confidence interval (CI) was computed and p<0.05 was considered as a level of significance.

Results:
The studies were homogeneous for all outcomes except all-cause mortality. There was no significant difference between EV and CV for post-procedural all-cause mortality (OR: 0.82, CI: 0.6-1.13, p=0.23), cardiovascular mortality (OR: 0.7, CI: 0.41-1.2. p=0.2), myocardial infarction (OR: 1.13, CI: 0.51-2.51, p=0.76), stroke (OR: 0.97, CI: 0.66-1.42, p=0.86) (Figure), major bleeding (OR: 1.13, CI: 0.81-1.58, p=0.48) and major vascular complications (OR: 1.22, CI: 0.94-1.58, p=0.14).

Conclusion:
The results of our meta-analysis of 6211 patients suggest that the types of valve used to perform TAVI procedures do not affect early mortality and MACCE outcomes. Further studies are needed to evaluate long-term outcomes.