bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 5400: Increase In Actin
O
-GlcNAcylation After Acute Exposure to N-Acetyl-D Glucosamine Influences Myofilament Calcium Sensitivity
Authors: Correa Genaro A Ramirez , Jin Wenhai , Wang Zihao , Xin Zhong , Gao Wei D , Hart Gerald W , Murphy Anne M
Published: July 2021

Recently, we have identified specific sites of
O
-GlcNAcylation in major cardiac myofilament proteins. We used a methodology based on GalNaz-Biotin labeling followed by DTT switch and LC-MS/MS site mapping. As a result, 42
O-
GlcNAc peptides from cardiac myofilaments were identified, corresponding to 32 of cardiac myosin heavy chain (MHC), 6 of α-sarcomeric actin, 2 of myosin light chain 1 (MLC1), 1 of MLC2, and 1 of troponin I (cTnI). Most of the identified
O
-GlcNAcylation sites are novel post-translational modification sites. To assess the potential physiological role of myofilament GlcNAcylation, Force-Calcium relationships studies were performed on skinned rat trabeculae. We have previously reported that exposure to GlcNAc but not Glycerol significantly decreases calcium sensitivity, further investigation confirm these preliminary findings (pCa 50 1.81 ± 0.13 μM for Control vs. 3.83 ± 0.44 μM for GlcNAc,
n
=7, P <=.001), and in addition demonstrate that maximal force (F
max
) and Hill coefficient (
n
) are not significantly changed. Troponin I phosphorylation at Ser23, 24 was determined in three pooled trabeculea by WB using a specific antibody phosphor-TnI (Cell Signaling) normalized to actin signal (GlcNAc 0.722 vs Glycerol 0.667 A.U., n=3, p=NS). Phosphorylation at this PKA sites was ruled out as responsible for myofilament desensitization. Acute exposure of cardiac myofilaments to GlcNAc significantly increased α-sarcomeric actin
O
-GlcNAcylation from 27.6±4.2% to 35.1±2.36% (
n
= 4, p<0.05) whereas total GlcNAcylation levels were unchanged. Additionally, we showed by immunofluoresence that O-GlcNAc transferase (OGT) and O-GlcNAcase (OGase) are abundant in rat hearts, OGT localizes predominantly in cardiac nuclei and less in cytoplasm, whereas OGase shows the opposite pattern. These studies provides the first site mapping of
O
-GlcNAcylation sites in cardiac myofilament proteins, and demonstrates their potential role in regulating myocardial contractile function. Regulation of myofilament
O
-GlcNAcylation may represent a novel and useful therapeutic target in heart failure, especially in diabetic cardiomyopathy.
Abstract 5445: Gli2 and Gli3 Are Over-expressed in the Ischemic Tissue and Participate in Ischemia-induced Angiogenesis and Myogenesis
Authors: Renault Marie-Ange , Roncalli Jerome , Tongers Joern , Hamada Hiromichi , Thorne Tina , Misener Sol , Ito Aiko , Clarke Trevor , Millay Meredith , Scarpelli Andrew , Klyachko Ekaterina , Losordo Douglas W
Published: July 2021

Gli transcription factors are mediators of hedgehog signaling and have been shown to be critical in several steps during development. In addition, Gli transcription factors have also been implicated as potent oncogenes. We have shown that the Hedgehog pathway is reactivated in the adult cardiovascular system under ischemic conditions and that the hedgehog pathway can be exploited therapeutically in ischemic disease; however the role and expression of the Gli transcription factors in the response to injury following ischemia have not been characterized. We induced hind-limb ischemia by resection of the left femoral artery of FVB mice and found that Gli2 and Gli3 mRNA were overexpressed in the ischemic tissue up to 4-fold and 9-fold respectively while Gli1 expression was not modulated. Immunostaining revealed that several cell types overexpressed Gli2 and Gli3 including myocytes and endothelial cells (ECs). To investigate the role and mechanism of action of Gli2 and Gli3,
in vitro
experiments were first performed. Overexpression of Gli2 and Gli3 promotes myoblast survival and proliferation. In ECs, overexpression of Gli2 and Gli3 promote survival and migration as well as induce expression of proteins involved in angiogenesis such as MMP-9 and osteopontin. To confirm the hypothesis of a favorable role of Gli2 and Gli3 in neovascularization and tissue repair following ischemic injury, adenovirus encoding LacZ, Gli2 and Gli3 were administrated locally in the tibialis anterior muscle, 2 days before hind limb ischemia surgery was performed. Both Ad-Gli2 and Ad-Gli3 treated mice exhibited higher proliferation in the regenerating muscle 7 days after ischemia. Moreover, Ad-Gli3 treated mice display higher capillary density (38.9±10.2 vessels/HPF vs. 26.1±6.1 in the control mice, p=0.012) and limb perfusion (the ratio of the perfusion of the ischemic leg vs. the control leg was 1.07±0.20 vs. 0.62±0,16 for the control mice, p=0.0003) 7 and 14 day after ischemia respectively. These data indicate that Gli2 and Gli3, transcription factors of the hedgehog pathway, are overexpressed in ischemic tissue and participate in tissue repair by promoting both neovascularization and proliferation and survival of myoblasts.
Abstract 5454: Oxidative Stress is Associated with Arterial Dysfunction and Enhanced Intima-Media Thickness in Children with Hypercholesterolemia. Potential Role of Nadph Oxidase
Authors: Loffredo Lorenzo , Martino Francesco , Carnevale Roberto , Sanguigni Valerio , Perri Ludovica , Martino Eliana , Catasca Elisa , Zanoni Cristina , Pignatelli Pasquale , Violi Francesco
Published: July 2021

Endothelial dysfunction and intima-media thickness (IMT) are precocious manifestations of hypercholesterolemia but the mechanism is unclear. The aim of the study was to analyse the interplay among endothelial dysfunction, IMT and oxidative stress in hypercholesterolemic children (HC). We performed a cross-sectional study comparing flow mediated dilation (FMD), IMT, lipid profile, urinary isoprostanes as markers of oxidative stress, and platelet expression of gp91phox, the catalytic unit of NADPH oxidase, in a population of 50 HC (mean age 10.0±3.7 years) and 50 normocholesterolemic children (NC) (mean age 9.2±3.5 years). Four children with hereditary deficiency of gp91phox were also studied. HC had reduced FMD (6.2±2.4 vs. 9.2±2.5%; p<0.001) and enhanced IMT (0.45±0.07 vs. 0.40±0.06 mm; p<0.002), urinary isoprostanes (86.9±51.6 vs. 45.9±25.6 pg/mg of creatinine; p<0.001) and gp91phox platelet expression (4.4±3.8 vs. 2.0±1.7 mean fluorescence; p<0.001) compared to controls. At bivariate analysis, FMD was correlated with LDL cholesterol (r= −0.448; p<0.001), IMT (r=−0.356; p=0.01), urinary isoprostanes (r=−0.388; p=0.005) and platelet gp91phox (r=−0.314; p=0.02). Stepwise multiple linear regression analysis showed that in HC, FMD and IMT were significantly associated with LDL cholesterol and urinary isoprostanes; also, gp91phox platelet expression was an independent predictor of urinary isoprostanes. Children with gp91phox hereditary deficiency showed down-regulation of platelet gp91phox and reduced urinary excretion of isoprostanes. The study suggests that gp91phox -mediated oxidative stress may have a pathogenic role in the anatomic and functional changes of the arterial wall occurring in children with premature atherosclerosis.
Abstract 5455: A Novel Haplotype on GCH1 Gene, Encoding GTP Cyclohydrolase 1, Regulates Vascular Biopterin Synthesis, eNOS Coupling and Vascular Redox in Human Vessels
Authors: Antoniades Charalambos , Shirodaria Cheerag , Guzik Thomasz , Van-Assche Tim , Pillai Ravi , Lotsch Jorn , Tousoulis Dimitris , Stefanadis Christodoulos , Tegeder Irmgard , Channon Keith M
Published: July 2021

Background:
GTP cyclohydrolase (GTPCH) is a key enzyme in biopterins synthesis, while tetrahydrobiopterin (BH4) is a regulator of eNOS coupling in vascular endothelium. A novel haplotype in GCH1 gene, combining dbSNPs: rs8007267G/A, rs3783641A/T and rs10483639C/G, affects GTPCH activity and biopterins levels in inflammatory cells. We examined the effect of this haplotype on vascular biopterins, eNOS coupling and redox state in human vessels from patients with coronary atherosclerosis.

Methods:
Samples of saphenous veins (SV) were obtained from 347 patients undergoing CABG. Vasorelaxations of SV to acetylcholine (ACh) and vascular O2- (± eNOS inhibitor LNAME) were determined. Biopterins were measured by HPLC. The haplotypes were defined as X (rs8007267A+ rs3783641T+ rs10483639G) or O (all other haplotypes).

Results:
The haplotype distribution was OO:245(71%), OX:95(27%) and XX:7(2%). Carriers of the X haplotype had lower plasma (Fig. a

) and vascular (Fig. b

) BH4. The X haplotype was associated with higher vascular O2- (XX+XO: 2.97±0.44 vs OO:1.90±0.10 RLU/Sec/mg, p<0.01), greater LNAME-inhibitable O2- (Fig. c

) suggesting eNOS uncoupling) and lower NO bioavailability (Fig. d

) in human vessels. The X haplotype was also associated with higher plasma ox-LDL (51.0±2.2 in XX+XO vs 44.2±1.4 U/L in OO p<0.05) and lower BH4:total biopterins ratio (43.1±3.2 in XX+XO vs 51.7±2.1% in OO, p<0.05).

Conclusions:
This novel haplotype on GCH1 gene regulates biopterins biosynthesis in both plasma and vascular endothelium. This haplotype also regulates eNOS coupling, O2- production and NO bioavailability in human vessels, and may play a role in atherogenesis.
Abstract 5464: CD40 Targeted Imaging of Atherosclerotic Plaque Lesions in ApoE−/− Mice
Authors: Grafe Michael , Dietrich Thore , Stibenz Dietger , Klohs Jan , Wunder Andreas , Lutgens Esther , Daemen Mat , Fleck Eckart , Graf Kristof
Published: July 2021

Active inflammation has been identified as major criteria for vulnerable atherosclerotic plaques. So far, they are not detectable by conventional diagnostic methods, such as coronary angiography. Therefore, we wanted to investigate whether molecules expressed in inflammatory, unstable plaques, such as CD40 receptor, can be used for molecular imaging and identification of such lesions. Monoclonal antibodies against CD40 were either coupled to cross-linked dextran-coated iron particles (CLIO) for MR imaging, or to the dye Cy5′5 for near-infrared fluorescence (NIRF) imaging. A matched IgG2A isotype antibody was used as negative control. ApoE−/− mice were fed for 4 month with high cholesterol diet and used as a model of atherosclerosis. Histological specimens of aortic tissues showed abundant expression of CD40 in atherosclerotic lesions of these animals. For NIRF imaging, either 25μg or 500μg Cy5′5-CD40 or Cy5′5-IgG2A were injected into the tail vein, and the aorta was imaged 6 and 24 hours after injection. For MR-imaging CLIO-CD40 (25μg/ml protein) or CLIO-IgG2A were injected and MR images were acquired 2 and 6 hours after injection using a 7 T scanner (Bruker). To prove the specificity of this approach NIRF imaging was also performed in double knockout Apo−/− CD40−/− mice High antibody concentrations (500μg Cy5′5-antiCD40) induced high fluorescence in the aortic wall and no difference to Cy5′5-control IgG2A at 6 and at 24 hours was detectable. Low concentrations (25μg) resulted in accumulation of fluorescence in Sudan-positive areas (r2=0.62) whereas low background fluorescence was detected after injection of Cy5′5-IgG2A (p < 0,05, n = 4) and in double knockout Apo−/− CD40−/− mice in the aortic arch. Fluorescence increased slightly after 24 hours compared to 6 hours after injection. Injection of CLIO-anti-CD40 induced a stable signal in the aortic arch in T2 weighted images of ApoE−/− mice compared to control CLIO-IgG2A. Detection of CD40 in atherosclerotic plaques with different imaging modalities is feasible. The approach might serve as a tool for detection of lesions with high inflammatory activity.
Abstract 5490: Cathepsin K Deficiency does not Affect Murine Aneurysm Formation However it Reduces Macrophage-Rich Neointima Formation in Apoe−/−Mice
Authors: Bai Lili , Lutgens Suzanne , Herias Veronica , Saftig Paul , Daemen Mat , Cleutjens Kitty , Biessen Erik , Heeneman Sylvia
Published: July 2021

Proteolytic arterial remodelling is a key process in various vasculopathies including restenosis and aortic aneurysm formation. One of the candidate effector proteases in both processes, may be cathepsin K (CatK), a potent lysosomal cysteine protease. We therefore hypothesized that a deficiency of this cystein protease could protect against these vascular pathologies. Firstly, we studied the effect of CatK deficiency on the intimal hyperplasia under normo-lipidemic (CatK−/− vs WT) and hyperlipidemic conditions (CatK−/−//ApoE−/− vs ApoE−/−) as induced by permanent ligation of the right carotid artery. Average neointima formation in hyperlipidemic CatK−/−//ApoE mice was significantly reduced compared to ApoE−/− mice (64%, p=0.02). Total vessel area was also significantly reduced in CatK−/−//ApoE−/− mice (46%, p=0.008 ). In contrast, catK deficiency did not affect SMC-rich neointima formation in normolipidemic mice as there was no difference in neointima size between CatK−/− mice and WT mice of C57BL/6 background. Secondly, we investigated the effect of CatK deficiency on angiotensin II-induced aneurysm formation in ApoE−/− mice. Contrary to our expectations, CatK deficiency did not protect against murine aneurysm formation. Strikingly, despite the similar aneurysm area, collagen content of aneurism lesions was 6-fold higher in CatK−/−//ApoE mice (p=0.04). Furthermore, we noticed a compensatory 71% and 90% increase, respectively, in the percentage of cathepsin S and cathepsin C positive cells in adventitia of CatK−/−//ApoE versus ApoE−/− mice (p=0.007 and 0.013, respectively). Taken these observations together, CatK deficiency appears to have divergent effects on restenosis and aneurysm formation only conferring protecting macrophage rich neointima formation in CatK−/−//ApoE−/− mice. Despite enhancing collagen content, CatK deficiency did not reduce aneurysm formation, which may be related to compensatory activation of other cathepsins in CatK deficiency. This also suggests that novel inhibitors selectively targeting CatK to intervene in pathogenic remodelling responses should be applied with caution.
Abstract 5509: Arginase Activity Mediates Vascular Inflammation
Authors: Caldwell Ruth B , Zhang Wenbo , Baban Babak , Rojas Modesto , Virmani Suvika , Patel Chintan , Smith Sylvia B , Romero Maritza , Caldwell Robert W
Published: July 2021

We have shown before that activity of NOX2 NADPH oxidase has a critical role in causing vascular inflammation. We have also shown that diabetes-induced vascular endothelial cell (EC) dysfunction is mediated by increases in arginase activity which decreases availability of L-arginine to EC nitric oxide synthase (eNOS). While the specific role of arginase activity in vascular inflammation is not yet clear, increases in arginase I levels have been described in conditions of elevated oxidative stress and inflammation. We have now used a model of endotoxin-induced retinal inflammation to assess the hypothesis that increased arginase activity is involved in the development of vascular inflammation. Mice were injected with lipopolysaccharide (LPS, 4 mg/kg, ip, 3–16 hrs). Measurement of urea formation showed that retinal arginase activity was increased in the LPS-treated mice (1.9±0.3-fold, n=5). Quantitative PCR showed that arginase I (AI) mRNA was also increased with a peak at 12 hrs (2.2±0.1-fold, n=3). Expression of the AII isoform was unchanged. Western blotting, immunohistochemistry and flow cytometry confirmed an increase in AI protein expression, which was localized to vascular cells, glia and microglia. AI expression and arginase activity were also increased in LPS-treated glia and microglia. The LPS-induced increases in AI expression were correlated with increases in mRNA for MCP-1 (575.1±84.8-fold, n=5), TNF-alpha (55.6±10.3-fold, n=4) and iNOS (103.3±1.5-fold, n=3) and with increased leukocyte adhesion to the vessel wall (5.5±1.5 fold, n=3–5). Studies using knockout mice deficient in one copy of the AI gene and both copies of AII or mice treated with the selective arginase inhibitor ([S]-[2-boronoethyl]-L-cysteine-HCl, 20 mg/kg, iv) showed that LPS-induced increases in inflammatory gene expression and leukostasis were blocked by knocking down or inhibiting arginase. Furthermore, the LPS-induced increase in AI was abrogated by NOX2 deletion or apocynin treatment, indicating involvement of NADPH oxidase activity. In conclusion, LPS-induced vascular inflammation is mediated by NADPH oxidase-dependent increases in arginase activity.

This research has received full or partial funding support from the American Heart Association, AHA Greater Southeast Affiliate (Alabama, Florida, Georgia, Louisiana, Mississippi, Puerto Rico & Tennessee).
Abstract 5525: Leptin Receptor Signaling Pathways are protective Against Atherosclerosis in a Mouse Model of Obesity and Hyperlipidemia
Authors: Luo Wei , Shen Yuechun , Wickenheiser Kevin , Öhman Miina , Myers Martin , Eitzman Daniel
Published: July 2021

Leptin is an adipocyte-derived hormone that has been shown to exert both beneficial metabolic effects and potentially adverse vascular effects in preclinical studies. To determine the effects of leptin receptor signaling pathways on atherosclerosis in the setting of obesity and hyperlipidemia, mice were generated with deficiency of apolipoprotein E (
ApoE
−/−
) and either wild-type leptin receptor expression (
Lepr
+/+
,ApoE
−/−
), mutant leptin receptor expression defective in all leptin receptor signaling pathways (
Lepr

db/db

,ApoE
−/−
), or mutant leptin receptor with selective deficiency of leptin receptor-STAT3 signaling (
Lepr

s/s

,ApoE
−/−
). At 27 weeks of age, which included 7 weeks on western chow,
Lepr

db/db

,ApoE
−/−
developed increased weight (61.9 ±3.5 vs 28±2.5, p<0.001), increased leptin (127.8±34 vs 24±12.5, p<0.003), increased NEFAC (2.4±0.75 vs 0.65±0.11, p<0.05) and more atherosclerosis (13.9±1.7 vs 4.3±0.9, p=0.001) than
Lepr
+/+
,ApoE
−/−
mice. In contrast, despite similar obesity and hyperlipidemia to
Lepr

db/db

,ApoE
−/−
mice, the atherosclerosis in
Lepr

s/s

,ApoE
−/−
was less than
Lepr

db/db

,ApoE
−/−
mice (7.3±1 vs 13.9±1.7, p=0.003) and not significantly greater than
Lepr
+/+
,ApoE
−/−
mice (7.3±1 vs 4.3±0.9, p=0.06 ). Hepatic steatosis and adipose inflammation were also reduced in
Lepr

s/s

,ApoE
−/−
mice compared to
Lepr

db/db

,ApoE
−/−
mice. In a mouse model of obesity and hyperlipidemia, leptin receptor signaling confers protection against hepatic steatosis, fat inflammation, and atherosclerosis. These effects are independent of leptin effects on energy balance.

This research has received full or partial funding support from the American Heart Association, AHA Midwest Affiliate (Illinois, Indiana, Iowa, Kansas, Michigan, Minnesota, Missouri, Nebraska, North Dakota, South Dakota & Wisconsin).
Abstract 5533: Interactions Between Inward Rectifier K
+
Current And Abnormal Calcium Homeostasis Contribute To Altered Bathmotropic Threshold And Increased Spontaneous Activity In Nos3
−/−
Mice
Authors: Sridhar Arun , Wang Honglan , Kohr Mark J , Carnes Cynthia , Ziolo Mark T
Published: July 2021

BACKGROUND: We have previously shown that there is prolonged action potential (AP) duration, greater L-type Ca
2+
current (I
Ca
), and enhanced spontaneous activity (early and delayed afterdepolarizations) during β-adrenergic (β-AR) stimulation in endothelial nitric oxide synthase knockout (NOS3
−/−
) myocytes. Altered repolarization and/or diastolic depolarization may contribute to spontaneous activity and arrhythmogenesis and earlier studies suggested a role for NOS3 modulation of K
+
channels.

HYPOTHESIS: We tested the hypothesis that NOS3
−/−
myocytes have altered K
+
currents.

METHODS: Ventricular myocytes were isolated from NOS3
−/−
and wildtype (WT) mice. APs; transient outward (I
to
), sustained (I
Ksus
) and the inward rectifier (I
K1
) K
+
currents were measured at 36±1°C.

RESULTS: No change in baseline AP duration or resting membrane potential was seen in NOS3
−/−
vs WT myocytes (p = NS). AP duration at 90% repolarization during β-AR stimulation was longer in NOS3
−/−
vs WT myocytes (102±11 msec vs 73±17 msec) consistent with our previous observations at room temperature. No differences in I
to
or I
Ksus
densities were seen between WT and NOS3
−/−
. The peak outward I
K1
current was not different between the two groups. Interestingly, NOS3
−/−
myocytes had a reduced I
K1
inward slope conductance vs. WT (0.27±0.005 vs. 0.34±0.001 mS/cm
2
; p<0.05). To address spontaneous activity in the setting of reduced inward I
K1
, further experiments to assess intra-sarcoplasmic reticulum (SR) calcium abnormalities were performed. A significant increase in β-AR stimulated SR Ca
2+
load (measured via caffeine) was found in NOS3
−/−
vs WT myocytes (56±18 vs 28±8 % of without isoproterenol, p<0.05).

CONCLUSION: We suggest that in NOS3
−/−
greater SR Ca
2+
load can cause spontaneous Ca
2+
release from SR, activating reverse mode Na
+
/Ca
2+
exchanger, an inward transient current. The combination of increased cytosolic Ca
2+
resulting from higher β-AR stimulated I
Ca
and SR Ca
2+
load, in concert with decreased inward I
K1
, provides a substrate for altered bathmotropic (excitability) threshold and arrhythmias in NOS3
−/−
myocytes. This may have important implications for arrhythmias and sudden cardiac death in heart failure, where NOS3 expression and I
K1
current are decreased.

This research has received full or partial funding support from the American Heart Association, AHA Great Rivers Affiliate (Delaware, Kentucky, Ohio, Pennsylvania & West Virginia).
Abstract 5544: Lymphotoxin β Receptor is Associated with Atherosclerosis in the Dallas Heart Study
Authors: Owens Andrew W , Matulevicius Susan , Rohatgi Anand , Ayers Colby R , Das Sandeep , Khera Amit , McGuire Darren K , De Lemos James A
Published: July 2021

Introduction:
Lymphotoxin β receptor (LTBR), a member of the tumor necrosis factor receptor family, is expressed by activated lymphocytes. Blocking LTBR improves autoimmune diseases and alters lipid homeostasis. We assayed circulating LTBR and examined its association with atherosclerosis in multiple vascular beds.

Methods:
Plasma LTBR was measured in 3215 subjects aged 30–65 enrolled in the Dallas Heart Study using an experimental ELISA assay (Biosite, Inc). Atherosclerosis was assessed using CT measurements of coronary calcium (CAC) (n=2462) and abdominal MRI measurements of aortic plaque (AP) (n=2252) and aortic wall thickness (AWT) (n=2265). We analyzed LTBR and atherosclerosis with uni- and multivariable logistic and linear regression methods.

Results:
The study cohort had median age 43; 44% women; and 70% non-white subjects. Higher levels of LTBR were associated with traditional cardiovascular risk factors and other inflammatory markers. Univariable analysis demonstrated modest associations with CAC (Spearman rho = 0.11, p<0.0001) and AWT (rho=0.16, p<0.0001). In multivariable models adjusted for traditional risk factors, the 4
th
vs. the 1
st
quartile of LTBR was associated with CAC > 10 (adjusted OR 1.4, 95% CI 1.01–1.95; Figure

); AP (OR 1.4, 95% CI 1.1–1.8; p=0.02); and increased AWT (β = 0.06, p<0.0001). Similar associations were observed when log transformed LTBR was used as a continuous variable.

Conclusion:
LTBR levels are independently associated with atherosclerosis in multiple vascular beds. These findings suggest a potential role of activated lymphocytes in the pathogenesis of atherosclerosis and warrant further investigation.
Abstract 5547: CXCR4 Signaling Exacerbates Vein Graft Neointimal Hyperplasia
Authors: Zhang Lisheng , Brian Leigh , Freedman Neil J
Published: July 2021

Vein graft neointimal hyperplasia can cause vein graft failure directly or, by promoting accelerated atherosclerosis, indirectly. Because most vein graft neointimal cells originate from outside the vein graft, and because CXCR4, the SDF-1α receptor, contributes significantly to recruitment of vascular progenitor cells, we tested the hypothesis that CXCR4 activity exacerbates vein graft neointimal hyperplasia. We performed carotid artery interposition vein grafting in congenic WT and
cxcr4
−/+
mice, using the inferior vena cava of WT and
cxcr4
−/+
mice as vein grafts. We created 3 surgically chimeric groups, designated by vein graft donor/vein graft recipient: WT/WT,
cxcr4
−/+
/WT, and
cxcr4
−/+
/
cxcr4
−/+
. Immunofluorescence for SDF-1, the CXCR4 agonist, was evident in 2-wk-old vein grafts (with expanding neointimas), but not in 6-wk-old vein grafts (in which neointimal hyperplasia had reached steady state). In 6-wk-old WT/WT,
cxcr4
−/+
/WT, and
cxcr4
−/+
/
cxcr4
−/+
vein grafts, respectively, neointimal areas were 0.12 ± 0.01, 0.118 ± 0.008, and 0.066 ± 0.008 mm
2
, while medial areas were 0.20 ± 0.02, 0.26 ± 0.01, and 0.32 ± 0.02 mm
2
. Thus, relative to WT/WT grafts, neointimal area was reduced only in
cxcr4
−/+
/
cxcr4
−/+
vein grafts, by 47% (
p
<0.01), while medial area was increased in
cxcr4
−/+
/WT and
cxcr4
−/+
/
cxcr4
−/+
vein grafts, by 26% and 56%, respectively (
p
<0.05). However, vein graft re-endothelialization was equivalent in all 3 vein graft groups (judged by immunostaining for Tie2). SMC-like cells comprised 100% of neointimal cells, but < 50% of medial cells. In
cxcr4
−/+
/
cxcr4
−/+
vein grafts, however, the prevalence of medial SMC actin-positive cells was 45±20% greater than in WT/WT grafts (p<0.04), while the prevalence of collagen I-positive cells was 40±5% less (p<0.01), as assessed by quantitative immunofluorescence. We conclude that CXCR4 contributes to vein graft neointimal hyperplasia through endothelium-independent mechanisms that alter homing of graft-extrinsic cells to the vein graft. Moreover, while CXCR4 activity augments neointimal hyperplasia, it reduces the medial hypertrophy that is believed to be desirable for reducing vein graft wall stress. These results suggest that CXCR4 antagonist therapy may alleviate vein graft disease.
Abstract 5558: MicroRNA Regulation of Endothelial Cell Growth
Authors: Yamakuchi Munekazu , Ferlito Marcella , Lowenstein Charles J
Published: July 2021

MicroRNAs (miRNAs) are short non-coding RNAs which inhibit gene expression at the post-transcriptional level. MiRNAs affect a wide variety of cellular functions such as proliferation, differentiation, and apoptosis, but the role of miRNA in endothelial cells is not well understood. The silent information regulator 1 (SIRT1) is an NAD-dependent deacetylase that regulates not only life-span but also cell growth arrest or apoptosis in response to oxidative and genotoxic stress. SIRT1 suppresses apoptosis thresholds by deacetylating molecular targets such as p53, FOXO transcription factors, and Ku70. We hypothesized that miRNA-34a regulates endothelial cell growth and senescence. We discovered that human endothelial cells (HUVEC and HAEC) express miRNA-34a by microarray analysis. When we over-expressed miR-34a in HUVEC, we found that SIRT1 protein was decreased. In contrast, transfection of HUVEC with antagomirs to miR-34a decreased endogenous miR-34a and increased SIRT1 protein. We identified a miR-34a binding site in the 3′ untranslated region (3′UTR) of SIRT1 and showed miR-34a directly inhibits SIRT1 translation using a luciferase assay. Next we examined the effect of miR-34a upon cell growth and senescence. Over-expression of miR-34a decreased SIRT1 protein, increased acetylated p53, and increased expression of p21, a transcriptional target of p53. When we co-transfected HUVEC with miR-34a precursor and SIRT1 expression vector to rescue SIRT1 expression, acetylated p53 and p21 expression were decreased. Finally over-expression of miR-34a induced cell cycle arrest and senescence in HUVEC using FACS and SA-gal assay. Our data suggest that miR-34a regulates cell growth and senescence through a SIRT1 - p53 pathway.
Abstract 5569: Paracrine Effects of Cardiomyocyte STAT3 Determine the Vasculogenic Differentiation Potential of Cardiac Progenitor Cells: Potential Role of Endogenous Erythropoietin
Authors: Fischer Philipp , Hoch Melanie , Stapel Britta , Drexler Helmut , Hilfiker-Kleiner Denise
Published: July 2021

Mice with a cardiomyocyte-restricted knock out of STAT3 (αMHC-Cretg/+; STAT3flox/flox, STAT3-KO) show a continuous decrease of cardiac vascularization and develop heart failure beyond the age of 9 months. We investigated the role of cardiomyocyte STAT3-driven paracrine effects on Sca-1+ cardiac progenitor cells (CPC) in the mouse heart. CPC were immunomag-netically isolated from KO and wildtype (STAT3flox/flox, WT) hearts (age: 3 months). PCR and Western blot confirmed deletion of STAT3 in cardiomyocytes of KO mice, while CPC from KO showed normal expression of STAT3. The total number of CPC per heart was similar between WT and KO mice. FACS analysis revealed a reduced number of endothelial progenitor cells (defined by co-expression of Sca-1, CD31 and CD38, −25%, P<0.05) in CPC from KO compared to CPC from WT. In vitro culture for 4 weeks on fibronectin-coated plates of CPC from KO revealed reduced proliferation (−33%, p<0.01), impaired endothelial cell (EC) tubeformation (monitored with Tie2, eNOS and CD31 immunohistochemistry (IHC), p<0.01) and enhanced adipocyte differentiation (oil red staining and RT-PCR, p<0.05) compared with CPC from WT. Microarray of freshly isolated CPC reflected this differences in EC and adipocyte differentiation on the mRNA level (i.e. EC marker Prostaglandin E Rezeptor-3: 2.3-fold lower; adipocyte marker Lipocalin-2 2.7-fold higher in CPC from KO hearts). Microarray results from whole left ventricular tissue showed a decrease in gene expression of Erythropoietin (Epo) in KO hearts (-9,25-fold). ELISA, IHC and methylcellulose assay confirm expression of active EPO by cardiomyocytes. CPC express high levels of EPO receptor (IHC, RT-PCR). Epo enhanced tube formation and sprouting of EC and attenuated adipocyte differentiation of CPCs from KO. In vivo treatment with Epo rescued impaired proliferation, promoted EC differentiation and attenuated adipocyte differentiation of CPC from KO hearts.

Conclusion: STAT3-dependent paracrine factors from cardiomyocytes regulate proliferation, differentiation and vasculogenic properties of CPCs. Cardiomyocyte derived EPO is an important paracrine mediator that promotes differentiation into EC and attenuates differentiation into adipocytes from CPCs in the adult heart.
Abstract 554: Measurement of Heart-Type Fatty Acid Binding Protein Identifies High Risk Patients among Those with Suspected Acute Coronary Syndrome Who Are Troponin Negative
Authors: Viswanathan Karthik , Morrell Christine , Thistlethwaite Susan J , Hassan Taj B , Barth Julian H , Hall Alistair S
Published: July 2021

To evaluate the role of heart-type fatty acid binding protein (H-FABP) in risk stratifying patients with suspected acute coronary syndrome (ACS), especially those identified as ‘troponin negative’. We recruited a consecutive cohort of 1080 consenting patients admitted with ‘suspected ACS’ over 10 months. Additional serum samples were collected 12–24 hours from symptom onset (same time as routine troponin test). H-FABP results, measured using the Randox assay, were available in 1047 patients. ‘Positive H-FABP’ was defined as ≥5.8μg/l (= 99th centile value in healthy adults with the Randox assay). Follow-up for mortality was for minimum of 12 months (for the last patient recruited). 1) 253/1080 (23.4%) were adjudged ‘troponin positive’(Siemens ultraTnI +ve). HFABP was positive (HFABP +ve) in 206/1047 (19.7%). All-cause mortality was 5.56% (64/1080). Mortality within sub-groups: TnI+ve 12.3% vs TnI −ve 4%; HFABP+ve 18% vs HFABP −ve 3.1%. 2) Among TnI −ve patients, 54/803 (6.7%) were HFABP +ve. Unadjusted mortality in TnI =−ve, ‘HFABP +ve’ patients was 18.5% vs 3.1% in TnI −ve, ‘HFABP −ve’ patients (HR 6.74 {95% CI = 2.8–16.6}, p <0.001) -see Figure. 3) After adjusting for age, serum creatinine, troponin and hsCRP in a multivariate model, elevated H-FABP was an independent predictor of all-cause mortality across the entire cohort [HR 2.38 (95% CI = 1.23–4.63), p=0.01]. Elevated H-FABP is an independent prognostic marker in patients with suspected acute coronary syndrome. H-FABP identifies high-risk ‘troponin-negative’ chest pain patients reliably and would be a useful adjunct when risk stratifying these patients.
Abstract 566: Critical Role of Ghrelin in Ventricular Remodeling after Acute Myocardial Infarction
Authors: Kondo Hideyuki , Hojo Yukihiro , Nishimura Yoshioki , Takahashi Nozomu , Ikemoto Tomokazu , Dezaki Katsuya , Katsuki Takaaki , Yada Toshihiko , Shimada Kazuyuki
Published: July 2021

Background: Ghrelin is a novel growth hormone (GH)-releasing peptide, originally isolated from the stomach, which has been identified as an endogenous ligand for the GH secretagogues receptor (GHS-R). Previous studies revealed that chronic administration of ghrelin suppresses cardiac sympathetic activity and prevents left ventricular (LV) remodeling after acute myocardial infarction (AMI). However clinical role of ghrelin after AMI is still not clear. We examined the role of ghrelin in LV remodeling after AMI.

Objectives: To elucidate the role of ghrelin in LV remodeling after AMI.

Subjects and methods: We employed patients with the first AMI (n=41, mean age 61.9±8.9 years old). We obtained peripheral blood on 1, 7, 14 days and 6 months after the onset. Plasma total ghrelin levels were measured by enzyme-linked immunosorbent assay. Patients were treated by percutaneous coronary intervention within 12 hours after onset. Successful myocardial reperfusion (TIMI flow grade 2 or 3) was accomplished in all patients. To analyze LV remodeling, all patients submitted to two serial left ventriculographies carried out on the day of admission and 6 months after the onset (mean 199±13 days). LV volume index (LVEDVI) was calculated by QCA-CMS software.

Results: Plasma total ghrelin levels increased after the onset of AMI (day 0: 28.4±6.4, day 7: 75.1±12.2, day 14: 89.9±14.8 pg/ml, 6months: 46.5±6.6 fmol/ml, p<0.001). There was a significant positive correlation between plasma ghrelin levels on day 14 after the onset and changes in LVEDVI (r=+0.53, p<0.001). The stepwise multivariate regression analysis showed that the plasma ghrelin level on day 14 is a significant explanatory variable for the changes in LVEDVI (F=8.77, p<0.01, β=+0.40).

Conclusions: The elevation of Ghrelin levels might be a compensatory mechanism to prevent LV remodeling. These results first indicate that ghrelin has a critical role in the progression of left ventricular remodeling after AMI.
Abstract 700: An Inhomogeneous Edematous Change in the Left Atrial Wall after Radiofrequency Ablation Predicts Early Recurrence of Atrial Fibrillation
Authors: Yokokawa Miki , Tada Hiroshi , Koyama Keiko , Naito Shigeto , Oshima Shigeru , Taniguchi Koichi
Published: July 2021

An inflammatory response following thermal injury from catheter ablation of atrial fibrillation (AF) may aggravate arrhythmogenic activity and cause early AF recurrences (ERAFs). In 56 patients with drug-refractory, paroxysmal AF (14 women, 60±10 years) who underwent circumferential pulmonary vein ablation (CPVA), cardiovascular magnetic resonance (CMR) was performed before, and 1 day and 1 month after the CPVA. The wall thickness, delayed enhancement (DE) and T2-weighted images of the LA wall were evaluated in 6 subdivided regions of the left atrium (LA; PV ostia, roof, anterior wall, posterior wall, septum, and mitral isthmus). Twenty-three patients (41 %) had AF recurrence within 1 month after the CPVA (ERAF-Gr), whereas the remaining 33 did not (No-ERAF-Gr). Before the CPVA, no region with a high T2 signal was found in any of the patients in either group, and no difference was observed in the total number of DE regions between the 2 groups (2±1 vs. 2±1, p=0.31). One day after the CPVA, high T2-weighted images were detected around the LA wall, and augmentation of the wall thickness of the LA roof was greater in the ERAF-Gr than No-ERAF-Gr group (see Table

). One month after the CPVA, the thickened LA wall with a high T2 signal recovered to baseline. On the other hand, the change in the total number of DE regions after the CPVA did not differ between the 2 groups. Shortly after the CPVA, the LA wall was characterized by interstitial edema concomitant with thermal injury, and an edematous change in the LA roof may predict an ERAF. CMR is useful for assessing the distribution and extent of the edematous changes of the LA wall after CPVA.

Change in the wall thickness and total number (no.) of scar regions 1 day after CPVA.
Abstract 703: Usefulness of Dual Doppler System in Estimating Left Ventricular Filling Pressure in Patients with Atrial Fibrillation -Temporal Analysis of Simultaneous Measurement of Transmitral Inflow and Mitral Annular Velocity-
Authors: Wada Yasuaki , Murata Kazuya , Tanaka Takeo , Nose Yoshio , Kihara Chikage , Fukagawa Yasuhiro , Yoshino Hiroko , Susa Takehisa , Matsuzaki Masunori
Published: July 2021

Background:

A ratio of early transmitral flow velocity (E) to early diastolic mitral annular velocity (E′) and a time interval between onsets of E and E′ (T
E′-E
) has been proposed as a novel index to assess left ventricular (LV) filling pressure (FP). However, in patients with atrial fibrillation (AF), it is often difficult to obtain steady Doppler-derived values because of fluctuating R-R intervals. Recently, simultaneous recording of E and E′, and calculation of E/E′ and T
E′-E
n each cardiac cycle has been feasible with dual Doppler system (Hitachi EUB7500).

Methods:

Forty patients with AF were analyzed to evaluate the feasibility for estimating LVFP by simultaneous recording of E and E′. We measured E/E′ and T
E′-E
corrected by R-R interval (cT
E′-E
) using a dual Doppler system, and LV pre-atrial pressure (pre-A) in 5 consecutive cardiac cycles.

Results:

E/E′ and cT
E′-E
had significant correlations with pre-A (E/E′: r=0.58, p<0.001; cT
E′-E
: r=0.78, p<0.001). The receiver-operating characteristic (ROC) analysis revealed that cut-off value of cT
E′-E
>34ms
0.5
had higher specificity and sensitivity to predicted pre-A>12mmHg than the value of E/E′ >10.1 (cT
E′-E
: sensitivity 94%, specificity 87%, E/E′: sensitivity 67%, specificity 43%).

Conclusions:

Even in patients with AF, the temporal analysis of E and E′ by the dual Doppler system was available for estimating elevated LVFP and provided an incremental value in addition to velocity analysis of pulsed and tissue Doppler indices.
Abstract 718: Head-to-Head Comparison of Apical Rotation versus Mitral Annular Systolic Velocity for Estimation of Global Left Ventricular Contractility
Authors: Kim Won-Jang , Seo Jeong-Sook , Min Sun Yang , Song Jong-Min , Kim Jae-Joong , Park Seong-Wook , Song Jae-Kwan
Published: July 2021

We sought to test whether mitral annular systolic velocity by tissue Doppler (S′) and apical rotation by speckle tracking echocardiography (AR) can represent global left ventricular (LV) contractility. We measured AR and S′ in nine open chest anesthetized mongrel dogs under eight different inotropic stages before and after ligation of left anterior descending (LAD, n=6) or circumflex coronary artery (LCX, n=3). We measured LV pressure simultaneously with a high-fidelity pressure catheter and calculated LV ejection fraction (EF) with the biplane Simpson’s method. Maximal positive dP/dt (dP/dt
max
) was used as the gold standard measurement of LV contractility. We compared AR and S′ and EF against dP/dt
max
by linear regression. Both S′ and AR showed dose-dependent increases and decreases following dobutamine and esmolol infusion, respectively. There was a stronger association between dP/dt
max
and AR (r=0.820,
P
<0.001) and S′ (r=0.784,
P
<0.001) than between dP/dt
max
and EF (r=0.567,
P
<0.001), and this trend was more apparent with coronary ligation. There was also a good correlation between AR and S′ with (r=0.690,
P
<0.001) and without (r=0.740,
P
<0.001) coronary ligation. Both AR and S′ are effective noninvasive indices of global LV contractility irrespective of coronary ligation and have better accuracy than LV EF.
Abstract 741: Larger Saphenous Vein Grafts in Relation to Native Artery are Associated with Reduced TIMI Grade 3 Flow but Improved Myocardial Perfusion at 1 Year: A PREVENT IV Analysis
Authors: Ciaglo Lauren N , Karmpaliotis Dimitri , Kunadian Vijayalakshmi , Gibson William J , Buros Jacqueline L , Zorkun Cafer , Lew Michelle E , Harrington Robert A , Palmer Alexandra M , Ogando Katherine J , Biller Leah H , Lord Erin E , Williams Scott P , Marble Susan J , Alexander John H , Gibson C. M
Published: July 2021

SVG patency is lower with smaller recipient vessel size (<2mm). However, the relationship between the presence of an over-sized or under-sized SVG relative to the native artery (NA) diameter at follow-up has not been fully explored. It was hypothesized that the presence of a larger SVG to NA diameter at 1 year follow-up would be associated with inferior antegrade flow in SVG and NA.

Methods

: Data were drawn from the PREVENT IV trial, a phase III, multicenter, randomized, double-blind, placebo-controlled trial in which autologous SVGs were treated
ex vivo
with edifoligide for patients undergoing CABG with repeat angiography within 18 months post CABG and films were evaluated by a core laboratory for SVG diameter, TIMI flow grade (TFG), TIMI frame counts (TFCs) and TIMI myocardial perfusion grade (TMPG).

Results:

The average ratio of SVG to NA diameter was 1.71±0.45 (n=1,945 in 1,203 patients). As the ratio of the SVG to NA diameter increased, the occurrence of optimal TFG 3 in the SVG was lower (Figure A

) and TFCs were higher (p=0.0001). The frequency of TFG 3 in the NA artery was also lower as the degree of mismatch between SVG and NA diameter increased (p=0.028). Conversely, as the SVG to NA mean diameter ratio increased, the occurrence of TMPG 3 was higher (Figure B

).

Conclusion:

Larger SVGs in relation to NA at 1 year follow-up were associated with slower flow but improved myocardial perfusion. Greater SVG diameter may be reflective of a larger SVG volume and may explain in part the longer time to fill the SVG; likewise the larger volume of the SVG may explain the apparent improved perfusion of the myocardium. Slower dye transit in large SVGs does not necessarily imply poor perfusion.
Abstract 751: Retrograde Acute Type A Aortic Dissection: Are Outcomes Worse Than Classic Acute Aortic Dissection?
Authors: Estrera Anthony L , Miller Charles C , Azizzadeh Ali , Lee Taek-Yeon , Abdullah Saad , Walkes Jon-Cecil , Safi Hazim J
Published: July 2021

Introduction: Recent reports of retrograde acute type A aortic dissection (RTAAD) following thoracic aortic endovascular repair have been associated with poor outcomes. This raises concerns about outcomes with RTAAD in general. We report and compare outcomes of retrograde acute Type A aortic dissection repair with classic acute aortic dissection (CAAD).

Methods: Between 8/1991 and 5/2008, we repaired 322 patients with acute type A dissection. This cohort was divided into two groups: RTAAD Group (52 cases), and CAAD Group (270 cases). RTAAD was defined as the presence of a dissection tear originating distal to the arch as identified intra-operatively. Tears in the ascending aorta denoted dissection as classic. Repairs using circulatory arrest were similar between groups, p>0.33. Preoperative, operative, and post-operative variables were analyzed retrospectively.

Results: Retrograde type A aortic dissection occurred in 16.1% (52/322) of patients. RTAAD differed from CAAD in the median time from initial symptoms to operation (75+−87 hours vs. 47+−61 hours) and specific presenting conditions. (See Table 1

) Outcomes (stroke: RTAAD, 2.1% vs. CAAD, 3.6%, bleeding: 4% vs. 9%, myocardial infarction: 6% vs. 6%, and mortality: 11% vs. 18%) did not differ significantly between the groups, p>0.05.

Conclusions: RTAAD presented later for repair and less frequently with redo-sternotomy and aortic valvular insufficiency. Despite these differences, outcomes from surgical repair did not differ significantly. Acceptable outcomes may be achieved with timely intervention.

Table 1:

Preoperative Variables
Abstract 760: Alterations in Fibroblast Phenotype during Murine Thoracic Aortic Aneurysm Development
Authors: Jones Jeffrey A , Zavadzkas Juozas A , Chang Eileen I , Koval Christine N , Stroud Robert E , Ikonomidis John S
Published: July 2021

Thoracic aortic aneurysms (TAAs) result from maladaptive remodeling of the vascular extracellular matrix (ECM). In addition to structural protein changes, resident cellular profiles are altered leaving the fibroblast as the predominant cell type within the vascular wall. The present study tests the hypothesis that fibroblast phenotype is also altered during TAA development. Primary murine aortic fibroblasts were isolated from normal (n=4) and TAA aortas (n=3; 4-wks post-induction; topical 0.5M CaCl
2
15 min) by the outgrowth method. Cultures were established and passages 3–5 were used for gene expression profiling in the absence of stimulation. Relative expression of 30 genes (MMPs, ECM proteins, transcription factors) normalized to 4 house keeping genes was measured by quantitative real-time PCR. Genes displaying a minimum 2-fold increase/decrease or genes with significantly different normalized Ct values (t-test, TAA vs. control; p<0.05) were considered to have altered expression Steady state gene expression of 4-wk TAA versus normal fibroblasts revealed elevated expression of
Mmp2, Mmp11, Mmp15, Col1a1, Col1a2, Col3a1, Eln, Lamb2, Fn1, Fbn2, Spp1, Sparc, Fos, and Fosb,
and decreased expression of
Mmp3, Timp3, Ltbp1, Sp1, and Junb
(
Figure

). This study demonstrates for the first time that isolated aortic fibroblasts from 4-wk TAAs possess a unique gene expression profile as compared to normal fibroblasts. This suggests they have undergone a stable phenotypic change, which may be the result of a clonal expansion of a subset of cells, and may play a significant role in TAA development through the enhancement of ECM proteolysis.
Abstract 820: Usefulness of Monitoring Congestive Heart Failure by Multiple Bioelectric Impedance Vectors
Authors: Khoury Dirar S , Naware Mihir , Siou Jeff , Mathuria Nilesh S , Wang Jianwen , Shih Hue-Teh , Nagueh Sherif F , Panescu Dorin
Published: July 2021

Bioelectric impedance is useful in detecting changes in pulmonary congestion and cardiac function. We examined the utility of simultaneously measuring multiple intrathoracic and intracardiac impedance signals by a cardiac resynchronization therapy (CRT) system for monitoring congestive heart failure (CHF). We implanted CRT systems in 15 normal dogs using standard leads. An additional LA pressure lead-sensor was implanted in 5 dogs. Continuous RV pacing (230–250 bpm) was applied over several weeks. Catheterization and echocardiography were performed biweekly. Multiple intrathorcaic and intracardiac impedance vectors were measured via ring (R), tip (T), coil (C), and Can electrodes. The system measured both steady-state impedance (Zs), which monitored changes in geometric and resistive parameters, and cardiogenic impedance (Zc), which monitored beat-to-beat variations during mechanical deformation of the heart. All animals developed CHF after 2– 4 weeks of pacing starting from baseline (EF, 43 vs. 31%; LV end-diastolic volume, 65 vs. 95 ml; LV end-diastolic pressure, 6 vs. 16 mmHg; LA volume, 18 vs. 31 ml; LA pressure, 8 vs. 26 mmHg). Zs decreased significantly during CHF in all measured vectors: LV
R
-Can, −17%; LV
R
-RV
R
, −15%; LV
R
-RA
R
, −11%; RV
R
-Can, −12%; RV
C
-Can, −7%; RA
R
-Can, −5% (LV
R
-Can reflected the largest change, p < 0.05). All Zs vectors decreased exponentially, but at varying time constants (7–13 days); the LV
R
-Can vector depicted the fastest rate of change (p < 0.008). Select Zs vectors reflected changes in LV end-diastolic volume; LV
R
-Can yielded the highest correlation (r = −0.83, p < 0.001). Zs was inversely related to LA pressure; the LV
R
-Can produced the highest correlation (r= −0.84, p < 0.001). Peak-to-peak Zc decreased significantly during CHF compared to baseline in all vectors tested (LV
R
-RV
R
, 18 vs. 11Ω; LV
R
-RA
R
, 20 vs. 13Ω; RV
R
-RV
T
, 38 vs. 13Ω). Changes in Zc via RV
R
-RV
T
correlated with EF (r = 0.72, p = 0.028). Intrathoracic and intracardiac impedance, acquired via different CRT system leads, have variable responses to CHF. Employing a LV lead improves physiologic monitoring by impedance. Cardiogenic impedance reflects dynamic changes in cardiac function during CHF.