bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 18115: Are State Policies to Permit Pre-hospital Bypass Associated With Better Treatment Patterns Among Patients With ST-Elevation Myocardial Infarction? A Report From AHA's Mission: Lifeline Program
Authors: Green Jacqueline L , Jacobs Alice K , Simon DaJuanicia N , Chiswell Karen , Blanco Rosalia , Bates Eric R , French William , Kupas Douglas F , Mears Greg , Roe Matthew , Nallamothu Brahmajee K
Published: March 2022

Introduction:
Early success with regionalization of STEMI care has led many states to adopt statewide pre-hospital STEMI destination policies, allowing emergency medical services (EMS) to bypass non-PCI capable hospitals. The association with adoption of these policies and patterns of care among STEMI patients is unknown.

Hypothesis:
Compared with similar states without STEMI bypass policies, we hypothesized states with bypass policies would have a higher proportion of eligible STEMI patients 1) arrive by direct EMS transport to PCI hospitals (less transfer-in); 2) receive any reperfusion; and 3) receive timely PCI.

Methods:
Using data from Jan 1, 2013 to Dec 31, 2014 from the NCDR ACTION Registry, six states with bypass policies (cases) were matched to six states without bypass policies (controls)
a priori
on region, hospital density, and percent state participation in the registry. Using the matched sample, logistic regression models were adjusted for patient- and state-level characteristics. Outcomes were: 1) transfer-in status, 2) receipt of reperfusion, and 3) receipt of timely PCI.

Results:
Case states: Delaware, Iowa, Maryland, North Carolina, Pennsylvania, and Massachusetts, were matched to the respective control states: South Carolina, Minnesota, Virginia, Texas, New York and Connecticut, with 19,287 patients at 379 sites. Patients from states with bypass policies were similar in age, gender, and comorbidities to patients from states without bypass policies. They were more likely to be white, have private insurance, and reside in rural areas. They were less likely to transfer into a PCI hospital (aOR=0.60, 95% CI 0.26-1.35) and more likely to receive reperfusion therapy (aOR=1.77, 95% CI 0.96-3.24), but these trends were not statistically significant. They were also significantly more likely to receive primary PCI within 90 minutes (aOR=1.59, 95% CI 1.19-2.12) or 120 minutes (aOR=1.44, 95% CI 1.06-1.95) of first medical contact.

Conclusions:
Statewide adoption of STEMI destination policies allowing EMS to bypass non-PCI capable facilities is associated with shorter time from first medical contact to PCI and non-significant trends toward increased arrival by direct EMS transport and more receipt of reperfusion therapy.
Abstract 18120: High Density Lipoprotein Particles Predict All-cause and Cardiovascular Mortality
Authors: Silbernagel Günther , Pagel Philipp , Pfahlert Volker , Genser Bernd , Scharnagl Hubert , Kleber Marcus E , Delgado Graciela , Ritsch Andreas , Grammer Tanja B , Baumgartner Iris , Koenig Wolfgang , März Winfried
Published: March 2022

Introduction:
The concentration and size of HDL particles are considered to be related to their atheroprotective properties. This study in patients at increased cardiovascular risk was performed to evaluate the associations of HDL particle characteristics with all-cause and cardiovascular mortality.

Methods and Results:
HDL particle concentrations for all sizes and for size categories (7-8.5 nm, 8.5-10 nm, 10-13 nm, and 13-16 nm) were measured in 2,290 participants of the LURIC study (1,575 males, 715 females) by nuclear magnetic resonance spectroscopy. Mean (standard deviation) age was 62.9 (10.4) years, body mass index was 27.6 (4.1) kg/m
2
, HDL cholesterol was 39 (11) mg/dl, and HDL particle concentration for all sizes was 25.1 (6.0) μmol/l. During a median (interquartile range) follow-up of 10.0 (6.1-10.6) years, 662 participants died from any cause and 434 from cardiovascular diseases. In multivariable analyses including adjustment for HDL cholesterol tertiles of HDL particle concentrations for all sizes were inversely related to all-cause (3
rd
vs. 1
st
tertile: HR [95%CI] = 0.69 [0.55-0.87], P=0.001) and cardiovascular mortality (HR [95%CI] = 0.67 [0.50-0.89], P=0.007). These associations were primarily mediated by the inverse relationship between the smallest HDL particles (7-8.5 nm) and endpoints (P≤0.005). The associations of larger HDL particles (8.5-10 nm, 10-13 nm, and 13-16 nm) with endpoints were less pronounced and did not reach statistical significance in multivariable analyses (all P>0.1).

Conclusions:
In participants of the LURIC study high concentrations of HDL particles predict decreased cardiovascular risk. This association is mainly driven by small HDL particles.
Abstract 18127: The Relationship Between Nonuniform Strut Distribution and Neointimal Coverage After Everolimus-eluting Bioresorbable Scaffolds Implantation
Authors: Sato Takao , Abdel-Wahab Mohamed , El-Mawardy Mohamed , Tölg Ralph , Richardt Gert
Published: March 2022

Objects:
The number and distribution of stent struts have been reported to affect neointimal coverage of metalic drug-eluting stent (DES). According to previous reports, the thick struts of everolimus-eluting bioresorbable scaffolds (BRS) created areas of low endothelial shear stress, which may contribute to neointimal formation. The aim of the present study is to investigate the relationship between the distribution of BRS struts and neointimal coverage.

Methods:
43 patients (50 lesions) underwent follow-up optical coherence tomography (OCT) 11.8 ± 2.6 months after BRS implantation. Cross sectional area (CSA) of OCT images were analyzed at 1-mm intervals. Scaffold area and neointimal thickness were evaluated. Additionally, scaffold eccentricity (SE) was defined as follows: SE = [maximum (Max) diameter - minimum(Min) diameter]/ Max diameter. Furthermore, to assess the impact of the strut distribution, CSAs of BRS were divided into four regions. The average neointimal thickness (ANT) and the number of strut in each region were measured. The number of strut in each region was classified into 1, 2, 3 and ≥4. Further, the ANT acquired in each area was divided by ANT of all struts in the same CSA to describe an unevenness score, and its Max and Min values were defined as Max-unevenness score and Min-unevenness score.

Results:
Mean scaffold diameter and length were 3.17±0.37 and 19.9±5.2 mm. In almost all cases, pre- (90%) and post- (80%) dilatation were performed at initial percutaneous coronary intervention. There was a significant difference in the unevenness score among regions with differenrt strut numbers (unevenness score=1,04±0.34 in regions with 1 strut (N=400); 0.97±0.25 in regions with 2 struts (N=616); 1.00±0.25 in regions with 3 struts (N=894);1.04±0.20 in regions with ≥4 struts (N=938); p=0.01). Furthermore, a significant correlation was observed between SE and the dispersion of neointimal coverage in each CSA, which was expressed as Max-unevenness score - Min- unevenness score (N=792, R=0.10, p=0.02).

Conclusion:
Unlike metallic DES, crowding of struts as well as spare distribution of struts is associated with increased neointimal proliferation after BRS implantation. In addition, SE might be associated with uneven neointimal coverage.
Abstract 18138: Endothelial PHD2 Loss Causes Pulmonary Arterial Hypertension via HIF-2
(Best of Basic Science Abstract)
Authors: Haase Volker H , West James , Kapitsinou Pinelopi P
Published: March 2022

Background:
Key mediators of cellular adaption to hypoxia are hypoxia-inducible factor (HIF)-1 and -2, which are regulated by the prolyl hydroxylases (PHDs). Although the HIF pathway has been shown to be involved in the pathogenesis of pulmonary arterial hypertension (PAH), little is known about the cell type-specific functions of the PHD/HIF axis in this context. Here, we used a genetic approach to specifically dissect the contribution of the endothelial PHD/HIF axis in PAH.

Methods:
Endothelial cell specific HIF activation was achieved by crossing Vecadherin (Cdh5)-Cre transgenics to Phd2 floxed mice (ePHD2), while the contribution of each HIF isoform was assessed by generating double mutants lacking PHD2 and HIF-2 (ePHD2HIF2) or PHD2 and HIF-1 (PHD2HIF1). Right ventricular systolic pressure (RVSP) was directly measured via insertion of a 1.4F Mikro-tip catheter transducer into a surgically exposed right internal jugular vein.

Results:
Mice deficient for endothelial PHD2 showed significant activation of HIF-signaling as shown by immunoblot analysis of lung tissue for HIF-1 and HIF-2. These mice developed spontaneous PAH (ePHD2: 54.3±6.9 vs Cre-: 24.8±2.2 mmHg, n=5-6, P=0.005) which was associated with right ventricular hypertrophy (RVH) (Fulton Index: 0.52 in ePHD2 vs 0.28 in Cre-, P=0.0004) and increased mortality. The PAH phenotype was maintained in ePHD2HIF1 mutants but was reversed in ePHD2HIF2 mutants. To assess the contribution of endothelial HIF-2 in hypoxia induced PAH, endothelial HIF-2 single mutants or Cre- littermates were exposed to normobaric hypoxia (10% O2) for 4 weeks. In contrast to controls, eHIF2 mutants were completely protected from development of PAH and RVH. Bone marrow transplantation studies showed no contribution from hematopoietic HIF-2 in hypoxia induced PAH.

Conclusions:
Our data establish that endothelial PHD2 loss results in PAH through a HIF-2 dependent mechanism. Our findings identify the PHD2/HIF2 axis as a potential target for PAH therapies.
Abstract 18146: Stress Speckle Tracking Imaging Parameters of Circumferential Deformation in Assesssing Ischemia for Patients With Moderate and High Probability of Coronary Artery Disease
Authors: Rumbinaite Egle , Vaskelyte Jolanta J , Zvirblyte Ruta , Vieželis Mindaugas , Lapinskas Tomas , Karuzas Arnas , Slapikas Rimvydas
Published: March 2022

Introduction:
Value of longitudinal strain and strain rate (SR) at rest and low dobutamine doses has been shown in small studies however little is known about circumferential strain, circumferential systolic and diastolic SR importance in early stages of dobutamine speckle tracking echocardiography (STE).

Hypothesis:
Hypothesis that circumferential strain, circumferential systolic and diastolic SR in early stages of dobutamine STE are markers of significant coronary stenosis in patients with moderate and high probability of coronary artery disease (CAD) was assessed.

Methods:
Dobutamine stress echocardiography and adenosine magnetic resonance imaging were perfomed to 101 patients with moderate and high probability of CAD. CAD was defined as ≥50% diameter stenosis on coronary angiography validated as hemodynamically significant by adenosine magnetic resonance. Patients were divided into two groups based on coronary angiography results: CAD (-) n=57 (56,44%) vs CAD (+) n=44 (43,56%). Circumferential strain, circumeferential systolic and early diastolic SR parameters at rest, low and high dobutamine doses were analysed using 2D STE.

Results and Conclusions:
There were no significant differences of clinical characteristics, conventional echocardiography and deformation parameters between the groups at rest. All analysed STE parameters at low dobutamine doses were significantly lower in patients wtih CAD (circumferential strain 23,84±7,25% vs 17,98±4,06%, p=0,01, circumferential systolic SR 2,70±0,74 s–1 vs 1,76±0,75 s–1, p=0,002; circumferential early diastolic SR 2,71±0,74 s–1 vs 1,76±0,75 s–1, p=0,002). Logistic regression analysis revealed that STE parameters at low dobutamine doses have significant predictive value for haemodinamically significant coronary stenoses. Circumferential strain, systolic and early diastolic SR obtained at low dobutamine doses are sensitive and specific markers of haemodynamically significant CAD.
Abstract 18158: Neointimal Coverage of Overlapping Everolimus-eluting Bioresorbable Scaffolds: An Optical Coherence Tomography Study in Native Coronary Arteries
Authors: Sato Takao , Abdel-Wahab Mohamed , El-Mawardy Mohamed , Tölg Ralph , Richardt Gert
Published: March 2022

Background:
Everolimus-eluting bioresorbable scaffolds (BRS) have thick struts, which could influence shear stress and neointimal formation. According to a previous report, the implantation of overlapping BRS has been associated with delayed coverage at 28-days after BRS implantaion. The aim of the present study was to investigate the relationship between BRS overlap and neointimal formation at long-term, using optical coherence tomography (OCT).

Method:
32 patients (35 lesions) treated with overlapping BRS underwent follow-up OCT at 11.8±3.0 months after percutaneous coronary intervention. Neointimal area and %uncovered strut were analyzed by OCT at the overlapping BRS site (OBS), non-overlapping proximal and distal BRS sites (NOPBS and NODBS, respectively). Neointimal area was defined as scaffold area - [lumen area + black box (strut)]. %neointimal area was defined as the neointimal areaх100/ scaffold area.

In addition, we evaluated the frequency of inter-strut invaginations (hollows) at OBS and non-overlapping sites, which have been suggested as a marker of abnormal vascular reactions to the eluted drug and/or the polymer. Hollows were counted if they exsisted in-between and outside apposed BRS struts.

Result:
Mean stent diameter and length of overlapped distal BRS and proximal BRS were 2.96±0.39 and 23.1±6.4mm, and 3.11±0.39 and 19.5±6.4mm, respectively. Mean overlap length of BRS was 2.5±1.3mm. At follow-up, %neointimal area was significantly higher at OBS compared to NODBS and NOPBS (35.1±7.8 vs. 20.1±6.2 vs. 21.3±7.6%, respectively, p=0.01). No correlation was observed between the overlap length and %neointimal area. Additionally, %uncovered strut of NODBS and NOPBS was similar to that of OBS. However, the frequency of hollows in OBS was significantly higher than in both NODBS and NOPBS (0.54±0.52 vs. 0.14±0.18 vs. 0.15±0.28/cross-section, respectively, p=0.02).

Conclusion:
The site of BRS overlap is associated with increased neointimal proliferation one year after implantation, which could be particularly important in patients with small vessels or diffuse coronary disease. Signs of abnormal vascular reactions might be more frequently observed at the site of overlapping BRS compared to non-overlapping site.
Abstract 18166: Increasing Endothelialization of BMS and DES With Intra-arterial AdVEGF-A Gene Therapy in Porcine Coronary Arteries
Authors: Hytonen Jarkko P , Halonen Paavo , Tarvainen Santeri , Taavitsainen Jouni , Kuivanen Antti , Koistinen Arto , Laakkonen Johanna , Hartikainen Juha , Yla-Herttuala Seppo
Published: March 2022

We aimed to increase stent endothelialization with gene therapy known to promote endothelial proliferation. In addition, we evaluated OCT and angioscopy imaging as tools for detecting endothelium with comparison to robust ex-vivo analyses including scanning electron microscopy (SEM), multiphoton microscopy and immunohistology.

24 stents, BMS and DES, were implanted into naïve porcine coronary arteries and received either AdVEGF-A or control AdLacZ gene therapy with a porous drug delivery catheter. Stents were imaged in-vivo with angiography, OCT and angioscopy immediately after stenting and one week and two weeks after stenting and gene therapy. At d14 the stents were collected for histology, multi-photon microscopy and scanning electron microscopy for assessment of endothelialization. Strut coverage was analyzed from SEM images and graded 0 (no coverage) to 3 (fully covered). Angioscopy pullbacks were analyzed for thrombus in the stented artery and graded similarly 0 (no thrombus) to 3 (occlusive thrumbus).

Initial SEM analyses from stented arteries two weeks after intervention showed increased strut coverage with BMS after VEGF-A gene therapy compared to control LacZ (2.8±0.4 vs. 1.8±0.4, p=0.0031, respectively, a) and b) in figure). Gene therapy did not change strut coverage in DES with stent coverage of 1.6±0.5 and 1.8±0.4, p=NS, AdLacZ and AdVEGF-A respectively. Angioscopic thrombus formation was low in all groups with a trend towards less thrombi on BMS groups (0.2±0.4 and 0.3±0.5 in AdLacZ and AdVEGF-A) compared to DES (0.8±0.8 and 0.8±0.7 in AdLacZ and AdVEGF, c) in figure with red thrombus at 4 o'clock).

AdVEGF-A treatment at the time of stenting increased coverage of BMS but did not improve healing of DES two weeks after stenting. Likely the strong cytotoxic drugs in DES hamper stent healing even with local supraphysiological growth factor concentrations. Angioscopy may be useful in assessment of arterial healing after treatment with a coronary stent.
Abstract 18178: Cardiotonic Steroid Lactone Ring Hydrolysis by Paraoxonases Attenuates Na/K ATPase Mediated Signaling
Authors: Kennedy David J , Levison Bruce S , Liu Jiang , Weber Malory , Agatisa-Boyle Brendan , Lim Mir , Shapiro Joseph I , Shih Diana , Lusis Aldons J , Hazen Stanley L , Tang W. H. Wilson
Published: March 2022

Introduction:
Cardiotonic steroids (CTS) such as marinobufagenin and telocinobufagin (TCB) are significantly elevated in chronic kidney disease (CKD) and heart failure and can directly lead to inflammation and cardiac fibrosis upon binding and signaling through the Na+/K+-ATPase. The 17β-lactone ring of CTS is critical for Na+/K+-ATPase binding. Paraoxonases are a family of hydrolytic enzymes which exhibit lactonase activity, although their physiologic substrate(s) are unclear. Decreased serum PON activity and increased levels of CTS are associated with increased oxidant stress and adverse clinical outcomes in the setting of HF and CKD, yet whether decreased PON activity is mechanistically linked to increased CTS levels is unclear.

Hypothesis:
We tested the hypothesis that PONs are capable of CTS hydrolysis and that hydrolysis of CTS to their open-ring form renders them inactive.

Methods/Results:
First we measured the ability of recombinant PONs to hydrolyze the lactone ring of active TCB to form open-ring TCB (ORT). Recombinant PON-1 (58.0±2.0 U/mg), PON-2 (0.49±0.01 U/mg) and PON-3 (10.8±0.6 U/mg) had specific lactonase activity for TCB as measured with a continuous pH sensitive colormetric assay. Further, plasma from PON-1 KO mice had a markedly diminished ability to open the 17β-lactone ring of TCB to form resulting ORT aldehyde as measured by a Purpald reagent assay, whereas plasma from PON1-overexpressing mice had increased production of ORT compared to wild type controls. Data from 86-Rubidium uptake experiments in LLC-PK1 cells demonstrated ORT had significantly reduced inhibition of Na+/K+-ATPase compared to TCB (0.25nM of TCB vs. 5000 nM of ORT, p<0.01). In both HK2 and human cardiac fibroblast cells, TCB but not ORT increased collagen-1 mRNA production in a dose dependent manner (1 to 100 nM, p<0.01). Finally, in plasma from CKD patients (n=22) both marinobufagenin (r2=0.58; p<0.01) and TCB (r2=0.31; p<0.01) levels were inversely proportional to lactonase activity, suggesting higher lactonase activity is associated with lower levels of CTS.

Conclusion:
These studies suggest CTS may be a novel physiologic substrate for PON and represent a previously unknown counter-regulatory mechanism of CTS in the setting of CKD and heart failure.
Abstract 18188: Chronic Obstructive Pulmonary Disease (COPD) and Alpha-1 Antitrypsin Deficiency (A1ATD) are Associated With Increased Aortic Inflammation and Stiffness
Authors: Fisk Marie , Cheriyan Joseph , McEniery Carmel M , Cockcroft John R , Rudd James H , Fryer Timothy D , Tal-Singer Ruth , Hopkinson Nicholas S , Polkey Michael I , Wilkinson Ian B
Published: March 2022

Introduction:
COPD is associated with increased cardiovascular events, even after adjusting for traditional risk factors. We hypothesised that this relates to aortic inflammation and stiffness, both surrogates of higher cardiac risk. For comparison, we also measured these parameters in A1ATD patients with emphysema and controls.

Methods:
Sixty subjects (24 COPD, 12 A1ATD, 12 smokers, 12 never smokers (controls)) were recruited. Aortic stiffness was estimated by aortic pulse wave velocity (aPWV). Aortic and carotid wall inflammation was measured by FDG PET/CT, with FDG uptake quantified as the target to blood ratio (TBR).

Results:
COPD and A1ATD subjects had both 1) increased aPWV compared to healthy smokers and controls (Table 1, p=0.01) and 2) more aortic inflammation, particularly in the abdominal aorta (p=0.0001, 24% and 29% difference to controls, respectively, Figure 1). FDG uptake was also higher in the carotid arteries of COPD but not A1ATD subjects (p=0.0001). There was no difference in stiffness between healthy smokers and controls (p=1.0), but arterial inflammation in the abdominal aorta was greater in smokers than controls (p=0.0001).

Conclusions:
COPD is associated with both increased aortic inflammation and stiffness. These mechanisms might explain the unexplained heightened cardiovascular risk in COPD patients and are potential therapeutic targets. A1ATD subjects also have increased aortic inflammation and stiffness suggestive of increased cardiovascular risk. Susceptibility to smoke injury in the lungs and vasculature, or systemic inflammation associated with lung disease, are possible explanations.
Abstract 18198: The Spleen Regulates Apoptotic Cell Clearance, Tissue Neovascularization, and Wound Healing After Myocardial Infarction
Authors: Mohamed Ismahil Mohamed Ameen , Patel Bindiya , Bansal Shyam S , Hamid Tariq , Goel Mehak , Zhong Hai , Zhou Guihua , Michaud Amy M , Prabhu Sumanth D
Published: March 2022

After myocardial infarction (MI), mononuclear phagocytes infiltrate the heart to orchestrate wound healing. The spleen is considered to be one reservoir for infiltrating immune cells. In chronic heart failure (HF), mononuclear splenocytes are pathologically activated and pro-inflammatory; however, their precise role in early post-MI healing is unclear. We hypothesized that the spleen is necessary for efficient tissue repair after MI, thereby limiting long-term pathological remodeling. Survival or sham splenectomy (Spx or nSpx) were performed in adult CD45.2 C57Bl/6 mice. One month later, Spx and nSpx control mice were subjected to left coronary ligation or sham operation (n=5-10/group), and post-MI remodeling was assessed at 24 h, 10 d, and 8 w. As compared with nSpx sham at 8 w, nSpx MI hearts exhibited significant (p < 0.01): 1) LV dilatation (EDV 112 ± 20 vs 50 ± 6 μL), 2) systolic dysfunction (EF 39 ± 25 vs 63 ± 12%); and 3) hypertrophy (LV/tibia length 10.6 ± 0.7 vs 7.7 ± 0.3 mg/mm). In contrast, as compared with nSpx MI, Spx MI hearts exhibited significant worsening (p < 0.05) of: 1) LV dilatation (EDV 163 ± 80 μL); 2) systolic dysfunction (EF 21 ± 10%); 3) hypertrophy (LV/tibia length 13.3 ± 0.8 mg/mm); 4) ~2-fold decrease in border zone (BZ) neovasculature by isolectin B4 staining; and 5) significantly reduced anti-inflammatory CD206+iNOS– BZ macrophages by immunostaining. Moreover, as compared with nSpx hearts 24 h post-MI, the infarct zone (IZ) of Spx MI hearts exhibited significant decreases in the subset of Tim4+ macrophages, which are primary mediators of apoptotic cell efferocytosis. Notably, Tim4+ macrophage levels in Spx MI hearts were restored upon adoptive transfer of mononuclear splenocytes from CD45.1 syngeneic mice 6 h post-MI. Lastly, at 10 d post-MI, as compared with nSpx, Spx MI hearts revealed reduced MMP9 activation, collagen deposition, and CD206+iNOS– macrophages in the IZ by immunostaining. Hence, we conclude that splenocytes regulate apoptotic cell clearance, tissue neovascularization, and wound healing after MI. Unlike chronic ischemic HF, where mononuclear splenocytes are pro-inflammatory and tissue-injurious, the cardiosplenic axis early after MI is necessary for wound repair and cardioprotective against adverse LV remodeling.
Abstract 18201: Effects of Epinephrine Administration on Cerebral Oxygenation During Cardiopulmonary Resuscitation
Authors: Deakin Charles D , Yang Jie , Nguyen Robert , Zhu Jiawen , Parnia Sam
Published: March 2022

Introduction:
Epinephrine has been presumed to improve cerebral oxygen delivery during CPR. Animal studies however have demonstrated that epinephrine-induced capillary vasoconstriction may actually decrease cerebral capillary blood flow and registry studies have suggested that adrenaline may actually worsen neurological outcome, The effects of epinephrine on cerebral oxygenation (rSO2) during CPR has not been documented in the clinical setting.

Methods:
Following ethics approval, rSO2 was measured continuously using cerebral oximetry in patients undergoing in-hospital cardiac arrest. During CPR, time event markers recorded the administration of 1mg epinephrine. rSO2% values were analysed for a 5 min window prior to and then 5 mins after the first epinephrine administration.

Results:
A total of 56 epinephrine doses were analyzed in 36 patients during CPR. Results are shown below. The average rSO2% in the 5 mins following epinephrine administration was 1.40% higher (95% CI=0.41-2.40%, P=0.0059) than in the 5 min period prior to epinephrine administration. After adjusting, for patients’ ROSC status, initial rhythm, hemoglobin and Charlson comorbidity index, this difference remained statistically significant (1.42% with 95% CI: 0.35-2.49%, P=0.009). There was no statistically significant difference in the gradient of rSO2% during the 5 min period immediately before (0.88) compared with immediately after (1.09) epinephrine administration.

Conclusion:
IV administration of 1mg epinephrine during CPR results in minimal changes to rSO2%. This is the first clinical data to demonstrate the effects of epinephrine on rSO2 and is consistent with animal studies. These results may go some way to explaining the limited effect of epinephrine on improving neurological recovery from cardiac arrest.
Abstract 18216: Essential Role of Platelet Glycoprotein Ibα Dependent Thrombin-FXI Feedback Loop in Arterial Hypertension, Vascular Dysfunction and Inflammation
Authors: Kossmann Sabine , Jäckel Sven , Jurk Kerstin , Ehlken Moritz , Lagrange Jérémy , Schönfelder Tanja , Knorr Maike , Brandt Moritz , Karbach Susanne H , Daiber Andreas , Oelze Matthias , Walter Ulrich , Renné Thomas , Ruf Wolfram , Münzel Thomas , Wenzel Philip
Published: March 2022

Interactions of platelets, leukocytes and the vessel wall play pivotal roles in activating coagulation and precipitating thrombosis. High levels of angiotensin II (ATII) cause arterial hypertension by a complex inflammatory pathway requiring leukocyte recruitment and reactive oxygen species production within the vessel wall coupled to vascular dysfunction.

Here we report an upregulation of tissue factor, thrombin-dependent endothelial cell VCAM-1 expression and integrin α4- and platelet-dependent leukocyte adhesion to arterial conductance vessels by ATII in vivo (1mg/kg/d for 7d). ATII-induced vascular dysfunction and Ccl2, VCAM-1 and Ly6C mRNA expression were ameliorated by thrombin inhibition, platelet-depletion as well as in hIL-4R/Ibα mice missing the extracellular ligand binding domains of GPIbα. Blockade of TF during ATII administration also attenuated vascular dysfunction and reduced vascular oxidative stress. Platelet rich plasma (PRP) of ATII-treated mice showed an increased thrombin evoked endogenous thrombin potential (ETP), whereas PRP from mice with pharmacological inhibition of FXI production or of hIL-4R/Ibα mice failed to amplify ETP following chronic ATII exposure. These data show that a FXI-dependent thrombin generation feedback loop requires GPIbα on platelets and suggest that TF-initiated coagulation promotes additional thrombin formation on platelets to cause vascular inflammation.

The therapeutic potential of blocking FXI synthesis via antisense oligonucleotides was generalized by experiments with 5/6 nephrectomized (5/6 Nx) rats. 5/6 Nx rats showed after 4 wk of surgery an endothelial dysfunction, increased blood pressure, vascular inflammation and oxidative stress, as well as a elevated ETP compared to sham whereas pharmacological inhibition of FXI synthesis attenuated these effects.

Our results reveal a critical role of platelet GPIbα to promote localized thrombin amplification and supporting a FXI-thrombin feedback loop in ATII-induced vascular inflammation. By using a FXI targeted approach, we propose a novel therapeutic possibility to interrupt this heterotypic cellular coagulation-inflammatory circuit.
Abstract 18234: Patient Participation in Cardiac Rehabilitation and Long-term Cardiovascular Events: A Population-based study
Authors: Medina-Inojosa Jose R , Somers Virend , Gomez Ibarra Miguel , Jean Nathalie , Thomas Randal , Shawn Leth , Daniels Stephanie , Lopez-Jimenez Francisco
Published: March 2022

Introduction:
Cardiac rehabilitation (CR) is recommended for secondary prevention following a coronary artery disease (CAD) event. The association between CR attendance and long-term major cardiovascular events (MACE)in the community has not been previously reported .

Hypothesis:
We tested the hypothesis that higher CR participation would be related to a lower risk of MACE,in residents of Olmsted county, Minnesota.

Methods:
We performed a community-based retrospective longitudinal study on patients referred to CR for CAD events or procedures between the years 2002 and 2012. Follow-up was performed using a record linkage system from the Rochester Epidemiology Project. CR participation was assessed as the number of CR sessions attended, and was analyzed as a continuous variable, as quintiles and also as a binomial variable using 12 sessions as the cutoff. The composite outcome MACE was defined as having an acute coronary syndrome (myocardial infarction (MI) or unstable angina), revascularization (CABG or PCI), ventricular arrhythmias requiring hospitalization, stroke or death from any cause. Multivariate models were adjusted for age and gender and also for factors associated with MACE in the univariate analysis.

Results:
Our cohort included 2273 patients, 69% males, mean age (SEM) 64 (0.26) years. After a mean follow-up of 6 (0.07) years, 827 patients had an event: MI (73), unstable angina (113), CABG(53), PCI (260), ventricular arrhythmia (13), stroke (72) and death (243). Participation in 12 or more sessions (vs <12 sessions) had a lower rate of MACE (HR 0.81, 95% CI 0.70-0.93, p=0.003, see
Figure1
. After adjusting for smoking, hypertension, diabetes and history of MI the association remained significant HR 0.85, 95% CI 0.74-0.98, p=0.03.

Conclusions:
A higher participation in CR was associated with a lower risk of MACE. These results provide additional evidence of important CR health advantages and expand on previous evidence of a dose-response benefit of CR.
Abstract 18260: Familial Beals- Hecht Syndrome Associated With Bicuspid Aortic Valve and Right Ventricular Apical Diverticulum. An Unusual Combination of Congenital Defects Diagnosed in Adulthood by Multimodality Imaging
Authors: Duarte Valeria E , Yousefzai Rayan , Paterick Timothy , Tajik A. Jamil
Published: March 2022

Introduction:
Congenital contractural arachnodactyly (CCA) is an autosomal dominant disorder. CCA is phenotypically similar to Marfan syndrome, typically not affecting the aorta or eyes. Right ventricle (RV) diverticulum with bicuspid aortic valve (BAV) and CCA is not described.

Case:
48 year-old caucasian female: cardiac apical aneurysm, scoliosis, BAV, and diagnosis of CCA. CCA affected her mother, brother, and daughter.

PE:
5’ 7", 128 pounds, scoliosis, arachnodactyly, wing span of 69”, Ghent Nosology score 5. Cardiac exam: unremarkable.
CT chest:
contrast: a 2.7 x 2.2 cm arterially enhancing thin-walled lobular structure at the cardiac apex communicating with RV.
Echo:
RV apical pouch: 2.2 x 1.7 cm, narrow neck - mild systolic expansion. RV size, function and strain: normal. BAV with trace AR. Ascending aorta: 3.5 cm. LVEF 73%.
Cardiac MRI:
2 x 2 x 2.5 cm diverticulum arising from the RV apex, 5 mm neck communicating with the aneurysm and RV. No delayed enhancement of the myocardium/ RV diverticulum.
Gene testing:
16 genes associated with familial thoracic aortic aneurysm and dissection tested. Patient: heterozygous for a novel D1532N variant in the FBN2 gene. This variant is not reported as a mutation or benign polymorphism.

Discussion:
CCA associated with BAV and RV diverticulum is not described. CCA is genetically linked to FBN2. Congenital ventricular diverticulum is a rare finding, very infrequently affecting the RV. Multimodality imaging and gene testing may lead to better identification of this malformation and its association with genetic diseases. There is no standardized treatment of RV diverticulum. This asymptomatic patient received conservative management.
Abstract 18264: Heart Rate Variability Predicts Mental Stress Ischemia in Patients With Stable Coronary Artery Disease
Authors: Shah Amit J , Quyyumi Arshed A , Kutner Michael , Bremner James D , Garcia Ernest , Nye Jonathon , Wilmot Kobina , Al Mheid Ibhar , Alkhoder Ayman , Isakadze Nino , Obideen Malik , Abdelhadi Naser , Pearce Brad , Long Qi , Lampert Rachel , Raggi Paolo , Vaccarino Viola
Published: March 2022

Introduction:
Mental stress ischemia (MSI) is an independent risk factor for cardiovascular outcomes and death in CAD patients, but little is known about the mechanisms behind this phenomenon. We hypothesized that alterations in autonomic function before, during, or after mental stress may play a role. We examined whether MSI positive patients with CAD have reduced parasympathetic (PNS) tone, as measured by high frequency heart rate variability (HF HRV), as well as reduced baroreceptor sensitivity (BRS), as approximated by low frequency (LF) HRV at baseline, peak mental stress, and recovery.

Methods:
A mental stress test with a standardized speech stressor was performed in 425 CAD patients wearing an ambulatory ECG monitor. Myocardial perfusion imaging was performed with TC-99m Sestamibi. After careful editing for artifacts and ectopic beats, HF HRV and LF HRV were measured for 5-min periods during a baseline rest period, 5 min of speech, and 5 min of recovery. Logistic regression was used to adjust for potential confounders.

Results:
The mean (SD) age was 63 (9) years, 26% were women, and 30% were African American; 42 (10%) patients developed MSI. Compared with MSI negative, MSI positive patients had lower HF HRV and LF HRV during rest, stress, and recovery. The largest difference was observed during stress; HF HRV was 46% lower (p=0.01), and LF HRV was 44% lower (p=0.01). When examining reactivity to stress (difference between stress and rest), only LF HRV was significantly different between groups, such that MSI positive patients had an average 32% reduction in LF HRV with stress, while MSI negative patients had an average 3% increase (p=0.04). LF HRV reactivity remained an independent predictor of MSI (p=0.01) in models adjusting for sociodemographics, traditional risk factors, antidepressants, beta-blocker use, revascularization history, heart failure, depression, posttraumatic stress disorder, and heart rate/blood pressure reactivity.

Conclusions:
Autonomic factors, most notably reduced LF HRV reactivity, predict MSI in CAD patients. This implies reduced BRS and autonomic inflexibility as an important pathophysiological component of the ischemic response to mental stress.
Abstract 18267: Ivabradine in Acute Heart Failure: A Therapeutic Means for Effective Heart Rate Control
Authors: Treptau Jens , Jeske Ole , Napp Christian , Menon Akshay , Schieffer Bernhard , Schaefer Andreas , Bauersachs Johann , Tongers Joern
Published: March 2022

Background:
In acute cardiac care elevated heart rates are related to morbidity and mortality. Heart rate control may be beneficial in critically ill patients, but heart rate-reducing ß-blockers or antiarrhythmic drugs alter inotropy and hemodynamics. We evaluated the use of ivabradine for heart rate control in acute heart failure with persistently elevated heart rates.

Methods/Results:
After acute ICU-admission for heart failure/cardiogenic shock, 68 patients (age 57+/-16 yrs, 49 male/19 female) were treated with ivabradine for heart rate control. ICU-admission resulted from myocardial ischemia (65%), decompensated heart failure (17%), valvular heart disease (4%) or other pathologies (7%); 17% of these patients had been resuscitated. Patients were critically ill: 29 required ≥1 catecholamine, 21 mechanical ventilation, 5 mechanical circulatory support (3 Impella microaxial pump, 1 extracorporal membrane oxygenation, 1 combined support), 4 received hemodialysis, and many a calcium sensitizer. In case of a persistently elevated heart rate after a 24hrs run-in phase (cut-off: >80bpm, mean 100±15 bpm), ivabradine was initiated on-top of standard care (dosing: 5 mg/d, n=15; 10 mg/d, n=53). In 10 patients, the ivabradine dose could be increased, while in only 3 patients the dose had to be reduced or therapy terminated. Ivabradine treatment resulted in a significant reduction of heart rate (baseline 100±25 bpm; ICU day-2 82±12 bpm, p<0.05; hospital discharge, 79±16 bpm, p<0.01) without hemodynamic alteration (systolic/diastolic blood pressure at discharge: 111±16/63±10 mmHg). Overall ivabradine was well tolerated. Apart from one individual, all patients survived the intrahospital phase. Five patients were successfully bridged to LVAD-implantation. Follow-up revealed that ivabradine was continued in 52% and 43% of patients 30 and 180 days after hospital discharge. No serious adverse events were reported. Three patients had to be readmitted with acute cardiovascular events within 30 days and another 3 within 180 days of follow-up, whereas 7 patients died during 180-days follow-up.

Conclusion:
Early addition of ivabradine to standard intensive cardiac care is efficacious and safe in controlling elevated heart rates in acute heart failure.
Abstract 18275: Serial Echocardiography Demonstrates Reversible Myocardial Dysfunction After Resuscitation From Cardiac Arrest
Authors: Jentzer Jacob C , Shafton Asher , Chonde Meshe , Hickey Gavin , Abu-Daya Hussein , Althouse Andrew , Rittenberger Jon
Published: March 2022

Introduction:
Reversible myocardial dysfunction after cardiac arrest (CA) appears common, but few studies have performed serial echocardiography in patients resuscitated from CA.

Hypothesis:
Evidence of reversible LV systolic dysfunction will be identified on serial echocardiography early after CA.

Methods:
We prospectively performed repeat transthoracic echocardiography (TTE) between 72 and 96 hours after CA in 17 patients who had undergone an initial TTE within 24 hours after CA. We compared mean values derived from 2D measurements, LVEF, spectral Doppler of mitral inflow and LV outflow, and peak systolic and early diastolic tissue Doppler of the mitral annulus between echocardiograms using paired t-tests. Mean changes in TTE parameters were compared between hospital survivors and non-survivors using paired t-tests.

Results:
In these 17 subjects, there were significant increases in LV fractional shortening (+0.12, p = 0.028), LV outflow tract velocity-time integral (+3.82cm, p = 0.002) and both septal (+2.6, p = 0.016) and lateral (+1.8, p = 0.014) mitral annular systolic tissue Doppler (s’) velocities on repeat TTE. There were nonsignificant increases in estimated LVEF (+11.25%, p = 0.063) and TAPSE (+0.32, p = 0.065) between initial and repeat TTE. Other TTE parameters did not differ significantly between initial and repeat TTE, although not all parameters were available in all patients. Hospital non-survivors had a significant decrease in their LV end-systolic diameter (-0.68cm, p = 0.0161) and a non-significant decrease in their LV end-diastolic diameter (-0.4cm, p = 0.0549) on repeat TTE, whereas survivors did not. Changes in both septal (6 vs. 1.5, p = 0.0044) and lateral (3.67 vs. 0.88, p = 0.0161) mitral annular s’ velocities were higher in non-survivors. Other changes in echocardiographic parameters did not significantly differ between survivors and non-survivors.

Conclusions:
LV fractional shortening, LV outflow tract velocity time integral and mitral annular s’ velocities increase between 24 hours and 72-96 hours after CA, consistent with reversible myocardial dysfunction. Hospital non-survivors had greater changes in LV dimensions and mitral annular s’ velocities between 24 hours and 72-96 hours than hospital survivors.
Abstract 18319: Virtual Mitral Valve Repair for Improved Pre-surgical Planning: Quantitative Evaluation of Neochordoplasty versus Leaflet Resection
Authors: Choi Ahnryul , Nguyen Tom C , McPherson David D , Kim Hyunggun
Published: March 2022

Background:
Neochordoplasty and/or leaflet resection are reliable and reproducible mitral valve (MV) repair techniques for the treatment of chordal rupture with severe mitral regurgitation (MR). We developed a novel computational evaluation strategy to determine the biomechanical and physiologic characteristics of MV dynamics prior to and following potential MV repair techniques to optimize surgical planning for neochordoplasty or leaflet resection.

Methods:
Virtual MV models from patients with P2 chordal rupture and severe MR were created using 3D echocardiographic data (N=5). Virtual neochordoplasty was designed by adding six neochordae between the papillary muscles and the P2 scallop. Virtual resection was performed by removing a pre-defined quadrangular shaped leaflet portion in the P2 scallop and merging the excised leaflet edges. Computational simulations of MV function (pre- and post-repair) were performed using dynamic finite element methods. Coaptation lengths and leaflet stress distributions were evaluated.

Results:
The MVs with P2 chordal rupture demonstrated severe P2 prolapse, leaflet malcoaptation, and large stress concentrations. Both repair techniques markedly reduced posterior leaflet prolapse and restored sufficient leaflet coaptation. Virtual neochordoplasty showed larger coaptation lengths (A2-P2) compared to virtual resection. Excessive stress concentrations in the P2 scallop disappeared and peak stress values decreased by up to 85% following both repair techniques.

Conclusion:
We have quantitatively evaluated patient-specific MV function before and after potential MV repair using a novel virtual MV repair protocol. Both virtual neochordoplasty and leaflet resection techniques decreased posterior leaflet prolapse, lessened stress concentration, and restored leaflet coaptation. This virtual simulation strategy has the potential for improved pre-surgical planning to optimize post-repair MV function.
Abstract 18325: Changes in Cognition and Lipid-lowering Therapy After the Acute Coronary Syndrome: Results From TRACE-CORE
Authors: Wanamaker Brett L , Swiger Kristopher J , Blumenthal Roger S , Saczynski Jane S , McManus David D , Waring Molly E , Kiefe Catarina I , Martin Seth S
Published: March 2022

Introduction:
Lipid-lowering therapies (LLT) are a key component of treatment in acute coronary syndrome (ACS). Some studies have found an adverse effect of LLTs on cognition yet evidence is inconsistent. We describe 12-month trajectories of cognition among ACS survivors in relation to post-discharge LLT use.

Methods:
Adult patients (n=2187) hospitalized for ACS in Georgia and Massachusetts enrolled in Transitions, Risks, and Actions in Coronary Events: Center for Outcomes Research and Education (TRACE-CORE) and underwent serial cognitive assessments from index hospitalization through 12 months via the Telephone Interview for Cognitive Status (TICS; range: 0-41; higher scores indicate better cognitive function). The primary outcome was change in TICS and unadjusted between-group comparisons were conducted using the two-sample T-test at 1, 3, 6, and 12 months. A multivariable linear model was constructed to examine the between-group comparison adjusted for baseline demographics, cardiovascular and in-hospital risk factors, and other comorbidities.

Results:
Participants were 67% male, 80% non-Hispanic white, and aged 61.4±11.3 years. Ninety-two percent were discharged on LLT. At 1 month follow-up (n=1527), patients improved on subsequent cognitive testing regardless of treatment with LLTs; mean TICS improvement was 1.0 for patients on LLT vs. 1.6 for those untreated (p=0.11). In adjusted models, change in TICS did not differ by LLT use (β= -0.41; 95% CI:-1.15, 0.33). Interval changes at 3, 6, and 12 months did not differ by LLT use, with complete follow-up cognitive testing available for 1345 patients (see figure).

Conclusions:
The prescription of LLT is not associated with the trajectory of cognitive function after hospital discharge for ACS. Despite concerns about the potential cognitive impact of lipid-lowering drugs raised by previous studies, our findings do not support an adverse impact on cognition among ACS patients treated with LLT.
Abstract 18333: Left Ventricular Systolic and Diastolic Dysfunction is an Uncommon Finding in a Pre-modern Society With High Inflammation and Low Atherosclerotic Risk Factors
Authors: Rowan Chris J , Sangodkar Sandeep C , Achrekar Abinash P , Tolstrup Kirsten , Beheim Brett , Stieglitz Jonathan , Trumble Ben , Gurven Michael , Kaplan Hillard
Published: March 2022

Introduction:
Ischemic cardiomyopathy from coronary atherosclerosis is the leading cause of mortality in developed nations. However, the natural history of cardiovascular disease in contemporary pre-industrial man is not well described. The Tsimane of Bolivia are a forager-horticulturalist population in the western Amazonian basin with high levels of inflammation and a low prevalence of atherosclerosis risk factors. We sought to define the cardiovascular health of a contemporary pre-industrial population with high inflammation and low atherosclerotic risk factors.

Methods:
Two-Dimensional echocardiograms with Color and Doppler were obtained on 934 Tsimane over age 40. Echocardiograms were reviewed by 2 cardiologists following the American Society of Echocardiography guidelines for interpretation. Patients had baseline clinical evaluations including age, height, weight, blood pressure, and gender. Blood was obtained for serology for inflammatory markers.

Results:
The average age was 53 years (SD +/- 11; range 40-90 years). 455 (48.7%) were male. The prevalences of hypertension, diabetes, and smoking were 4.8%, 0.5%, and 1.3%, respectively. Mean LVEF was 66% (SD +/- 6.1). There were 4 males with LVEF less than 52% and 11 females with LVEF less than 54%. There was no measured LVEF less than 44%. Complete diastolic data was available in 910. Normal diastolic parameters were observed in 741 (81.4%). Mild diastolic dysfunction was found in 167 (18.3%) and moderate dysfunction in 2 (0.2%). No echocardiograms showed severe diastolic dysfunction. Serologic data showed elevated CRP, ESR, and IL-6 with low high density lipoprotein (HDL) and low density lipoprotein (LDL)

Conclusions:
In a pre-modern population with high inflammation and low atherosclerotic risk factors, cardiovascular systolic and diastolic dysfunction was a rare finding.