bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 5570: β-2 Adrenergic Receptors Overexpression Promotes Angiogenesis in the Failing Myocardium through Activation of Vascular Endothelial Growth Factor/Akt Transduction Pathway
Authors: Zincarelli Carmela , Rengo Giuseppe , Maugeri Fondazione S. , Golino Luca , Altobelli Giovanna G , Cimini Vincenzo , Fortunato Francesca , Marchese Massimo , Femminella Daniela , Avallone Elena , Rengo Alessandro , Rengo Franco , Maugeri Fondazione S. , Koch Walter J , Leosco Dario
Published: July 2021

β-2 adrenergic receptor (β-2AR) plays a pivotal role in endothelial cell proliferation and promotes angiogenesis in response to hindlimb ischemia. Desensitization/uncoupling of cardiac β-2AR represents a well established phenomenon in heart failure (HF). In this study we aimed to investigate the role of β-2AR in the impairment of angiogenic processes occurring in the failing myocardium. To this purpose, we explored the angiogenic effects of β-2AR in a rat model of post-myocardial infarction (MI) HF. Cardiac adenoviral-mediated β-2AR overexpres-sion has been obtained via direct intramyocardial injection (4 x 10
11
PFU) 4 weeks after MI. We also extended our observation to β-2AR knockout (β2KO) mice developing HF after large anterior MI (infarct size 45 ± 6%). Cardiac β-2AR overexpression in HF rats markedly increased capillary and arteriolar length density, and induced larger left ventricular (LV) hypertrophic responses than that observed in untreated HF animals. Such LV adaptive remodelling was associated to reduced LV diameters and improved cardiac LV fractional shortening (FS) and +dP/dt. At molecular level, cardiac β-2AR gene transfer induced sustained activation of p-Akt and S6 kinase (S6K) phosphorylation and increased p-eNOS and VEGF levels that were instead reduced in untreated HF rats. In β2KO mice, we found a ~25% reduction of cardiac capillary and arteriolar density compared to WT mice. In β2KO mice, MI was associated with a dramatically higher 21-day mortality compared to WT (70% vs 30%, respectively). Survivors β2KO mice showed increased LV end diastolic and systolic diameters, and worse global cardiac contractility compared to controls. Cardiac Akt activation, S6K phosphorylation, p-eNOS, and VEGF-A production were significantly blunted in HF β2KO mice.

Conclusions. β-2ARs play an important role in regulating angiogenic responses in post-MI HF hearts. The activation of Akt signal transduction pathway seems to be strongly involved in these mechanisms.
Abstract 5572: Endothelial-Selective Deletion of Neuregulin-1 Leads to Impaired Tolerance of Ischemic Injury
Authors: Huang Qunhua , Kalinowski April , Jafri Kashif , Palmeri Monica , Russell Raymond R , Russell Kerry S
Published: July 2021

The neuregulin-1 (NRG)/erbB signaling axis is emerging as an important mediator of endothelial/myocyte crosstalk. We have previously shown that NRG can protect cardiac myocytes from apoptosis induced by hypoxic injury and that endothelial cells can provide this NRG in an ex vivo co-culture model. To extend this observation to an intact animal system, we have generated mice with inducible and endothelial-selective deletion of NRG. We hypothesized that animals with decreased endothelial NRG expression would be more susceptible to ischemic injury. Mice carrying a transgene for tamoxifen-inducible expression of cre recombinase under control of the Tie2 promoter were crossed with those carrying homozygously floxed NRG-1 genes. Serial echocardiographic measurements of cardiac function were performed before, during and after tamoxifen induction. There was no significant decrease in cardiac function following the completion of the induction (NRG knockout) protocol. Hearts from these mice underwent a global ischemia/reperfusion protocol in the Langendorff mode. Both resting and post-ischemic +/−dP/dT and left ventricular developed pressure were impaired in the animals with endothelial selective NRG deletion compared to non-induced transgenics or tamoxifen-induced controls. Hearts from the NRG deleted animals released more CPK and contained significantly more apoptotic nuclei compared to controls after ischemia/reperfusion, supporting the idea that endothelial-derived NRG can protect myocytes against apoptosis in vivo. Another mechanism by which loss of NRG may contribute to cardiac dysfunction in the setting of ischemia is by altering cardiac myocyte glucose uptake. We have shown that adult rat cardiomyocyte glucose uptake is significantly increased in response to NRG and that this response is abrogated partially by wortmannin, but completely by wortmannin plus compound C (an inhibitor of AMP-activated protein kinase), suggesting that both AKT and AMPK dependent pathways of glucose uptake may be activated by NRG in adult myocytes. Thus, we conclude that NRG plays an important role in preservation of cardiac myocyte function in vivo and that this may occur as a result of both protection against apoptosis and enhanced glucose metabolism.
Abstract 572: Hyperglycemia and Poor Outcomes in Patients without Diabetes Mellitus in the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS): A Propensity Matched Analysis
Authors: Deedwania Prakash C , Pitt Bertram , Carbajal Enrique V , Ahmed Ali
Published: July 2021

Background:
The effect of hyperglycemia on outcomes in patients with acute MI (AMI) and low LVEF without diabetes mellitus is not well known.

Methods:
In the EPHESUS trial, of the 4411 non-DM patients, 554 had baseline hyperglycemia (≥140 mg/dL). Propensity scores for hyperglycemia were calculated for each of the 4411 patients based on 63 baseline covariates, and a greedy 1:8 matching protocol was used to match 400 and 2542 patients respectively with and without hyperglycemia. Matched Cox regression models were used to estimate associations between hyperglycemia and outcomes during 16 months of follow up.

Results:
Patients with hyperglycemia were more likely to be older, have higher heart rate, lower LVEF, and receive nitrates, statins, digoxin, loop diuretics, and PTCA during index admission. Unadjusted hazard ratios {HR} and 95% confidence intervals {CI} for hyperglycemia were: all-cause death (1.51; 1.22–1.87; P<0.001), cardiovascular (CV) death (1.52; 1.21–1.90; P<0.001), heart failure (HF) death (2.19, 1.46–3.29; P<0.001), all-cause hospitalization (1.23; 1.08–1.40; P=0.002), CV hospitalization (1.51, 1.24–1.84; P<0.001) and HF hospitalization (1.75; 1.37–2.25; P<0.001). In the matched cohort, hyperglycemia was significantly associated with CV death (HR=1.25, 95%CI=1.01–1.54; P=0.039), sudden cardiac death (HR=1.33; 95%CI=1.02–1.73, P=0.035) and fatal/nonfatal AMI (HR=1.53, 95%CI=1.07–2.19; P=0.04; Figure

).

Conclusions:
In non-diabetic post-AMI HF patients, hyperglycemia is a poor prognosticator and is associated with increased risk of fatal and non-fatal AMI, CV death, HF deaths, sudden cardiac death, and CV hospitalization.

Figure

Fatal or non fatal acute myocardial infarction (AMI) by baseline serum glucose in post-AMI patients with no known history of diabetes mellitus
Abstract 577: Long Pentraxin 3: A New, Independent Marker of Mortality in Acute Chest Pain
Authors: Kontny Frederic , Brügger-Andersen Trygve , Staines Harry , Grundt Heidi , Miyamoto Kyoko , Miyazawa Chihiro , Matsuura Tadashi , Sagara Mina , Nilsen Dennis W
Published: July 2021

Long Pentraxin 3 (PTX3) is a newly identified member of the Pentraxin protein family that includes C-reactive protein (CRP). Unlike CRP, PTX3 is produced by the major cell types involved in atherosclerotic lesions in response to inflammatory stimuli. Increased PTX3 levels are found in acute coronary syndromes (ACS). Its role in long-term prediction of clinical outcome is, however, unknown. The aim of the current study was to assess the predictive value of PTX3 concerning all-cause mortality in patients hospitalized for acute chest pain. Plasma PTX3 was measured with a new, high-sensitive ELISA method (PPMX, Tokyo, Japan) in blood samples taken on admission in 784 patients admitted for acute chest pain suggestive of ACS. The patients were followed for 24 months concerning clinical outcome. For statistical analysis, the study cohort was divided into quartiles according to PTX3 levels. A multiple logistic regression model was fitted to include standard risk measures. At 24 months follow-up 121 patients had died. By logistic regression, the odds Odds Ratio for death among patients with highest PTX3 levels was 3.13 as compared to those with lowest levels (p=0.007) (table). Long Pentraxin 3 is a new, independent marker that strongly predicts long-term all-cause mortality in patients with acute chest pain.
Abstract 587: A Randomized Study Evaluating Outcomes of Cardiopulmonary Resuscitation in Rats with Myocardial Infarction Treated with Three Delivery Methods of Mesenchymal Stem Cells
Authors: Wang Tong , Wan Zhi , Tang Wanchun , Sun Shijie , Huang Zitong , Weil Max Harry
Published: July 2021

We investigated the effect of allogeneic mesenchymal stem cells (MSCs) on myoardial function following cardiopulmonary resuscitation (CPR) in a rat model of myocardial infarction. We further investigated the efficacy of three routes of MSCs administration including intravenous, intraventricular and intramyocardial injection. Regardless of administration routes, MSCs would improve myocardial function after CPR in myocardial infarction animals. Myocardial infarction was induced by ligation of the left anterior descending coronary artery in 54 rats (6 groups, 9 rats for each). One month later, animals were randomized to receive injection of 5×10
6
MSCs labeled with PKH26 or PBS alone as a placebo into right femoral vein or left ventricular cavity or the infarction zone in the anterior ventricular free wall. Four weeks after injection, 6 minutes of untreated ventricular fibrillation (VF) followed by 6 minutes of CPR were performed prior to defibrillation. Hemodynamics, including cardiac index (CI), dp/dt40, −dp/dt and left ventricular diastolic pressure(LVDP) were measured before induction of VF (baseline) and hourly following resuscitation. There were siginificant improvements in CI, dp/dt40(Figure 1

), −dp/dt, LVDP after CPR in MSCs treated animals, regardless of the sites of injection. Survival time after CPR was siginificantly increased in MSCs trearted groups comparing with the corresponding PBS treated groups. Independent of administration routes, myocardial function and survival time after CPR were comparably improved in all groups treated with MSCs in constrast to the PBS groups.

Figure 1
Abstract 588: Extracorporeal Cardiopulmonary Resuscitation for Induction of Hypothermia in Patients with Out-of-Hospital Cardiac Arrest
Authors: Nagao Ken , Kikushima Kimio , Watanabe Kazuhiro , Tachibana Eizo , Mukouyama Takaeo , Tominaga Yoshiteru , Tada Katsushige , Chiba Nobutaka , Kasai Asuka , Soga Taketomo , Matsuzaki Masakazu , Nishikawa Kei , Tateda Yutaka , Ikeda Harumi , Yagi Tsukasa
Published: July 2021

Therapeutic hypothermia is beneficial to neurological outcome for comatose survivors after out-of-hospital cardiac arrest. However, there are few data of extracorporeal cardiopulmonary resuscitation (ECPR) for induction of hypothermia for patients with out-of-hospital cardiac arrest. We did a prospective study of ECPR with hypothermia for patients with out-of-hospital cardiac arrest. The criteria for inclusion were an age of 18 to 74 years, a witnessed cardiac arrest, collapse-to-patient’s-side interval <15 minutes, cardiac arrest due to presumed cardiac etiology, and persistent cardiac arrest on ER arrival in spite of the prehospital defibrillations. After arrival at the emergency room, cardiopulmonary bypass plus intra-aortic balloon pumping was immediately performed, and then coronary reperfusion therapy during cardiac arrest was added if needed. Mild hypothermia (34°C for 3 days) was immediately induced during cardiac arrest or after return of spontaneous circulation. We selected suitable patients who received conventional CPR with normothermia among a prospective multi-center observational study of patients who had out-of-hospital cardiac arrest in Kanto region of Japan “the SOS-KANTO study” for the control group. The primary endpoint was favorable neurological outcome at the time of hospital discharge. A total of 558 patients were enrolled; 127 received ECPR with hypothermia and 431 received conventional CPR with normothermia. The ECPR with hypothermia group had significantly higher frequency of the favorable neurological outcome than the conventional CPR with normothermia group (12% vs. 2%, unadjusted odds ratio, 8.1; 95% CI; 3.2 to 20.0). The adjusted odds ratio for the favorable neurological outcome after ECPR with hypothermia was 7.4 (95% CI; 2.8 to 19.3, p<0.0001). Among the ECPR with hypothermia group, early attainment of a target core temperature of 34°C increased its efficacy (adjusted odds ratio, 0.99; 95% CI; 0.98 to 1.00, p=0.04). ECPR with hypothermia improved the chance of neurologically intact survival for adult patients with out-of-hospital cardiac arrest, and the early attainment of a target temperature enhanced its efficacy.
Abstract 591: Can Waveform Characteristics Predict Defibrillation to a Perfusing Rhythm in Short Versus Prolonged Ventricular Fibrillation in a Swine Model?
Authors: Indik Julia H , Zuercher Mathias , Kern Karl B , Hilwig Ronald W , Berg Robert A
Published: July 2021

It is known that defibrillation of ventricular fibrillation (VF) to a perfusing rhythm (ROSC) is more likely to occur in VF of short duration. It is unknown whether ROSC can be predicted by waveform characteristics in VF of short compared to long duration, apart from a consideration of time alone. VF was untreated for 2 minutes (N=10) or 8 minutes (N=10) in normal swine, after which a defibrillation shock was applied. Chest compressions for two minutes were allowed following but not prior to the shock to achieve a perfusing rhythm (ROSC). VF was analyzed from needle electrodes prior to the shock for amplitude spectral area (AMSA), slope, median frequency and bandwidth. Predictors of ROSC were determined by logistic regression. In VF of 2 minute duration 7 out of 10 swine achieved ROSC compared to 2 out 10 swine with VF of 8 minutes (P=0.025) and time was a significant predictor of ROSC (P=0.033). AMSA was significantly higher at 2 minutes (75 ± 18 mV-Hz) compared to 8 minutes (56±11 mV-Hz, p=0.007) as was slope (3.5±1 vs 2.6±0.5 mV/s, p=0.015). Bandwidth was slightly increased from 2.2±0.6 Hz at 2 minutes to 2.8±0.8 Hz at 8 minutes,(p=0.048), while median frequency was similar. However, no waveform characteristic was a significant predictor of ROSC, with substantial overlap in distributions between animals with and without ROSC. Duration of VF is an important determinant of the likelihood of achieving ROSC with defibrillation. Particularly in VF of short duration, VF waveform characteristics do not add to the predictability of achieving ROSC even though they may demonstrate a significant time evolution.
Abstract 595: Functional, Histologic, and Radiographic Characteristics of Global Ischemia-reperfusion Brain Injury in a Mouse Model Of Cardiac Arrest
Authors: Pendyal Akshay , Dezfulian Cameron , Zhang Luhua , Munasinghe Jeeva , Gladwin Mark T
Published: July 2021

Cardiac arrest (CA) and subsequent CPR constitute a clinically relevant form of global ischemia-reperfusion injury (IR). Global IR often results in widespread ischemic brain damage and severe neurologic sequelae. In the present study, we sought to describe the functional, histologic, and radiographic brain changes that occur following CA/CPR. 8–10 week old C57BL/6 mice were subjected to 12 minutes of normothermic cardioplegic CA and resuscitated with chest compressions, mechanical ventilation, and epinephrine. Sham mice underwent surgery, but not CA. At 3 and 24 hours, 10-point functional neurological score and rectal temperature were assessed prior to trans-cardiac perfusion with PBS and 10% buffered formalin. Sectioned brains were stained using hematoxylin and eosin (H/E) and the terminal deoxyuridine triphosphate nick end-labeling (TUNEL) technique. An additional cohort of mice underwent quantitative diffusion MRI at 24 and 72 hours, gadolinium (Gd)-enhanced MRI at 24 hours, and quantitative T2 imaging at 72 hours. Compared to shams, mice undergoing CA/CPR displayed significantly lower functional neurological score at 3 hours (3±2 vs. 10±0; P<.001) and 24 hours (8±1 vs. 10±0, P<.05), and significantly higher rectal temperature at 3 hours (35.8±1.5 vs. 34.1±0.8, P<.001) and lower rectal temperature at 24 hours (33.8±2.5 vs. 37.1±0.8, P=.08). TUNEL and H/E staining revealed injury in the cortex, thalamus, hippocampus, and cerebellum, but neither a consistent pattern nor clear temporal progression was observed. Gd-enhanced MRI revealed increased signal intensity, particularly in the cortex, after CA (3.7×105±0.96×105 vs. 0.66×105±0.017×105, P<.05), consistent with breakdown of the blood-brain barrier. Diffusion MRI revealed a strong trend towards globally decreasing diffusion coefficients at 24 and 72 hours (P=0.14), consistent with widespread cell death. In our model of CA, global IR results in poor neurological function and global injury by MRI that is not reflected by early histology. MRI thus appears to be a more sensitive measure of visualizing neurological injury in the early stages after CA and may predict the delayed neuronal death remarked upon by other authors.
Abstract 635: The Proximal AV Bundle in the Human Heart and Related Morbidity
Authors: Racker Darlene K
Published: July 2021

INTRODUCTION: The proximal AV bundle (PAVB) has been shown to be the only input to the AV node (AVN) in the canine heart in anatomoelectrical reports over the past 20 years. The anatomic studies utilized photographic correlations of epi- and endocardial aspects of whole hearts through blocking, and serial histologic parallel, perpendicular and transverse plane Goldner Trichrome stained sections of the flattened heart; Karnovsky’s fixative at pH 7.2 and sucrose buffer rinses; direct 3D and stereotaxic analysis. Electrical studies, under direct observation of in-vitro superfused hearts, delineated unique wire, catheter, and micropipet electrode potentials via high K, transections, Lucifer Yellow iontophoresis and photoablations during spontaneous and paced SA node rhythms and with simultaneous SA node, atrionodal bundles, PAVB, AVN and distal AV bundle recordings.

HYPOTHESIS: The PAVB exists in the human heart.

METHODS AND RESULTS: Explanted normal human hearts, deemed unsuitable for transplantation, processed as above with transverse sections, revealed that the AVN (Figs. A–C

) is joined by the PAVB at a 90-degree angle (Figs. B, C

). These “normal” hearts from older patients (57– 80 yr) had atrophic or absent atrial myocardium. In Figure C

, most of the right medial atrial wall myocardium, but not the left atrium (LA), had been replaced by fat.

CONCLUSIONS: PAVB is the only AVN input in the human heart. As in the canine heart, PAVB also runs away from the annulus and is apposed to LA. Knowledge of the PAVB should be helpful in decreasing morbidity associated with clinical procedures. Care must be taken in ablating the fast superior atrionodal bundle pathway input to the PAVB.

Figures

A
and
B
are from the same 60 yr and
C
is from a 71 yr old heart. AVN (A) is apposed to the left ventricular outflow tract (LVOFT and dotted line) along with the PAVB (
B and C
). But as seen in
C
, PAVB assumes a position apposed to LA, And, as in the dog heart, thereafter (not shown here) PAVB is completely apposed to LA.
Abstract 685: Atherosclerotic Plaque Composition Among patients with Stenotic Coronary Artery Disease on Non Invasive Coronary CT Angiography
Authors: Feuchtner Gudrun , Jodocy Daniel , Cury Ricardo C , Friedrich Guy , Blumenthal Roger S , Budoff Matt , Nasir Khurram
Published: July 2021

Coronary CT angiography (CCTA) has emerged as a promising non-invasive tool to rule out significant coronary artery disease (CAD) as well provides additional information about atherosclerotic plaque composition. In this study we aim to assess the whether differences in plaque composition exist across patients with varying degree of stenotic CAD disease. The study population consisted of 548 subjects (58±11 years, 45% women) referred for 64-slice multi-detector CCTA for assessment of underlying degree of coronary artery disease. We analyzed plaque characteristics on a per-segment basis according to the modified AHA classification. Plaques types were classified as non-calcified, calcified, mixed type 1 (predominantly non-calcified) or mixed type 2 (predominantly non-calcified). Overall 194 (35%) had normal coronaries without evidence of plaque. In the remaining 354 patients, 187 (34%) and 167 (31%) were found to have luminal narrowing of <50% and ≥70% in at-least one coronary artery segment, respectively. Those with a higher degree of stenotic CAD demonstrated significantly more coronary segments with exclusively calcified and mixed plaques (table

). Among those with significant CAD, the overall proportion of plaque burden was more likely to be mixed predominantly calcified (18% vs. 38% vs. 44%) as well as mixed predominantly non-calcified in nature; whereas were less likely to be exclusively non-calcified (39% vs. 20% vs. 16%). Only 3/208 (1.3%) patients without any underlying calcification had significant CAD (stenosis ≥50%). In summary, significant differences in plaque composition according to severity of CAD were observed in our study with a higher mixed plaque and lesser non-calcified plaque burden among those with stenotic CAD. These findings should stimulate further investigations to assess the prognostic value of plaque according to their underlying composition.
Abstract 697: Dyssynchrony in Duchenne Muscular Dystrophy Demonstrated by Tagged MRI Analysis is Independent of Ejection Fraction
Authors: Gottliebson William M , Mazur Wojciech , Wansapura Janaka , Benson D. W , Hor Kan N
Published: July 2021

Patients with Duchenne Muscular Dystrophy (DMD), a dystrophinopathy, universally develop dilated cardiomyopathy, which is associated with abnormal myocardial strain, as well as heterogeneous development of fibrosis as demonstrated by pathology and more recently by cardiac MRI methods. We sought to determine the presence of systolic dyssynchrony in this population using cardiac MRI tagging methods. We analyzed tagged MRI images for the presence of dyssynchrony in 61 males (age 12.5 ± 4.4 y) with a dystrophin mutation undergoing clinical cardiac MRI. Tagged MRI images were analyzed using HARP® analysis of regional strain and strain-time curves. The mid-myocardial slice was specifically analyzed, by dividing it into 6 coronary perfusion regions. Dyssynchrony was defined by the presence of either of 2 previously published indexes modified for use with MRI data: 1) time difference of 1
st
to last regional peak strain > 100 ms; 2) standard deviation of time differences to peak strain for each of the six regions > 33 ms. Additional indexes evaluated included heart rate, LV ejection fraction, mid-myocardial composite circumferential strain, and presence of delayed myocardial hyperenhancement (MDE). Among the 61 subjects analyzed, 28 (46%) exhibited dyssynchrony indexes 1 and 2, while 8 additional subjects met dyssynchrony index 2 but not index 1. Only 4 subjects, all of whom met both dyssynchrony criteria, had positive MDE and abnormal EF <55%. The regions of slowest activation were highly dispersed and not clustered to the areas of positive MDE. One additional subject with dyssynchrony by either of the critieria also had abnormal EF but did not have MDE. There was no statistically significant difference between mean EF (61 vs 62%), age (12.58 vs 12.63 yrs), heart rate (105 vs 108 bpm) or mid-myocardial composite circumferential strain (−13.3 vs −12.9%) between those subjects with dyssynchrony (by either criteria) and those without. DMD patients frequently exhibit systolic dyssynchrony even in the presence of normal EF. However, the dispersed nature of the dyssynchrony suggests that resynchronization therapy once EF becomes abnormal is unlikely to be of benefit in DMD cardiomyopathy.
Abstract 717: Spatial And Temporal Nonuniformity Of The Normal Left Ventricle During Isovolumic Contraction And Ejection By 2D Speckle Tracking Imaging
Authors: Hodt Anders , Stugaard Marie , Hisdal Jonny , Stranden Einar , Atar Dan , Steine Kjetil
Published: July 2021

Background:
The main purpose of this study was by novel 2D speckle tracking imaging (STI) to determine regional distribution of circumferential shortening, rotation and torsion (twist) and their relation to area ejection fraction (EF) during isovolumic contraction (IVC) and ejection phases in the normal left ventricle (LV).

Methods:
Twelve healthy subjects (22 ±3 years) were included. M-mode of atrio-ventricular level was used to describe LV longitudinal shortening, while circumferential strain, rotation and area EF were determined at four different LV short axis levels (basal, papillary, sub-papillary, apical) by STI. LV torsion was calculated as apical minus basal rotation.

Results:
See figure

. During IVC, LV torsion demonstrated an “untwist pattern”, and LV shortened more in longitudinal than in circumferential direction. During ejection, the counter clockwise rotation increased from papillary level towards apex, −0.4 ± 3.3° and 9.6 ± 3.4° (p<0.05), respectively, while circumferential shortening was larger in apex than papillary level, −25.4 ± 5.0 and −19.3 ± 2.4% (p<0.05), respectively. EF increased from papillary level to apex, 52 ± 6.1 % and 65 ± 8.4 % (p<0.05), respectively.

Conclusion:
This study has showed a regional nonuniform pattern of rotation and circumferential shortening, with corresponding changes in regional EF in normal LV through systole. The increased counter clockwise rotation and circumferential shortening towards apex during ejection may be of mechanistic importance for distribution of blood towards LV outflow tract. The greater extent of longitudinal- than circumferential shortening and untwisting suggest a LV spherical form during IVC.
Abstract 729: A More Accurate Method for Automatic Segmentation of Left Ventricular Mass by SPECT
Authors: Soneson Helen , Ubachs Joey , Ugander Martin , Arheden Håkan , Heiberg Einar
Published: July 2021

Background:
Accurate quantification of left ventricular mass (LVM) by single photon emission computed tomography (SPECT) is important when analysing LVM as such, but also when estimating the relative size of a perfusion defect. Existing algorithms for segmentation of LVM by SPECT have undergone limited validation. The aim of this study was to develop and validate a new segmentation algorithm for LVM by SPECT, and compare the new method to the commercially available software Quantitative Gated SPECT (QGS).

Methods:
98 patients with known or suspected coronary artery disease underwent both rest and stress SPECT and MR. The new method was trained in 20 patients (40 studies) and tested in 78 patients (156 studies) by comparing LVM in both rest and stress SPECT with manually segmented LVM by magnetic resonance imaging (MRI) as the reference standard. The new method was compared to results from QGS.

Results:
The mean difference ±SD in LVM between SPECT and MRI was lower for the new method (6±15 %LVM) compared to QGS (18±19 %LVM) for both mean difference (p<0.001, t test) and SD (p=0.01, F test), see Figure

.

Conclusion:
The new method quantifies LVM with a significantly lower bias and variability compared to the commercially available QGS software, when compared to manually segmented LVM by MRI.
Abstract 818: A Novel Electrophysiological Model Using Hybrid X-Ray/MRI and Non-Contact Mapping to Estimate Electrical Recruitability of Myocardial Tissue
Authors: Chinchapatnam Phani , Ginks Matthew R , Sermesant Maxime , Rhode Kawal , Arridge Simon , Lambiase Pier D , Bostock Julian , Rinaldi C A , Razavi Reza
Published: July 2021

Introduction
CRT is established therapy for patients with symptomatic heart failure, poor LV function & evidence of dyssynchrony.

Hypothesis
CRT outcomes may be improved by understanding of patient-specific conduction through electrical recruitability (ER) maps of the LV which can be derived from LV electrical activation (EA) data & electrophysiology (EP) models.

Methods
Patients scheduled for CRT underwent cardiac MRI in our hybrid X-ray/MRI (XMR) laboratory to delineate scar using late gadolinium enhancement (LE). An EP study was performed in the same procedure. An Eikonal EP model was used to predict propagation wavefronts in different pacing modes. ER was defined as the square of the tissue space constant of EA & was estimated by an adaptive algorithm by matching the simulated to the recorded activation times. Activation maps were recorded in various pacing modes using non-contact mapping (NCM).

Results
Ten patients underwent combined MRI & EP study. Fig 1a

shows the estimated ER for a patient with activation recorded in sinus rhythm (SR) & corresponding % thickness LE from cardiac MRI (Fig 1b

). The correspondence of low recruitability areas (blue) to positive LE areas is evident. Further, an endocardial paced isochronal map was then predicted using the EP model with the SR ER map (Fig 1c

) & compared against NCM isochrones obtained (Fig 1d

) pacing in that position.

Conclusion
We have shown the proof of concept for estimating the electrical recruitability of myocardial tissue. Such maps may provide insights into the electrical properties of the tissue and assist in prediction of activation patterns resulting from pacing and may have a role in optimization of CRT pacing lead positions.

Fig. 1.

Bull’s eye plots for a patient with ischemic cardiomyopathy, posterolateral scar and LBBB. LV apex at centre of each diagram and basal segment on outside; anatomical orientation as indicated in (a) top left; Electrical recruitablility (units=mm
3
) obtained in sinus rhythm (b) bottom left: percentage wall thickness of late enhancement (LE) (0=no LE; 1= full thickness LE) (c) top right; predicted isochronal map (earliest in red to latest in blue, units= msec) for LV endocardial pacing based on estimated recruitability and (d) bottom right corresponding measured activation pattern measured using NCM. (IVS: Interventricular septum)
Abstract 825: Effect of Cardiac Resynchronization Therapy on the Timing of Regional Myocardial Deformation
Authors: Miyazaki Chinami , Powell Brian D , Redfield Margaret M , Espinosa Raul E , Bruce Charles J , Rea Robert F , Miller Fletcher A , Oh Jae K
Published: July 2021

Background:
Effect of CRT on the timing of regional myocardial strain is not fully described. We aimed to explore the effect of CRT on the timing of regional myocardial strain using speckle tracking echocardiography (STE).

Methods:
STE and tissue Doppler imaging were performed in 91 patients before and 6 month after CRT. Time to peak longitudinal strain (Tϵ) from the onset of QRS was measured in 16 segments from three apical views. Time to peak systolic tissue velocity (Tv) was also measured in 12 basal and mid segments. Reverse remodeling was defined as 10% reduction in end-systolic volume.

Results:
At baseline, Tϵ and Tv demonstrated specific pattern with earlier septal and delayed lateral contraction (Figure

). Tϵ in responders showed significantly earlier timing in mid inferoseptal (p=0.003) and anteroseptal segments (base, P=0.005, mid P=0.007) than in nonresponders, whereas the timing of free wall did not differ between responders and non-responders. After CRT, Tϵ in earlier segments (inferoseptal, anteroseptal and inferior wall) prolonged significantly (p<0.001), whereas other segments did not change timing. Accordingly, SD of Tϵ in 12 segments reduced after CRT (110±46 ms vs. 81±36 ms, p<0.001). Tv did not change in all segments and SD of Tv did not improve after CRT (43±16 vs. 46±16 ms, p=0.20).

Conclusions:
Simultaneous electrical activation of LV free wall and septum with CRT achieves mechanical synchronization by delaying the timing of earlier contracting segment rather than directly shortening the timing in lateral wall. This could be explained by the increased wall stress on the septum as it contracts simultaneously with the opposing LV free wall.

Figure.

Change in Regional Timing in Strain and Peak Velocity
Abstract 835: Left Ventricular Expression of Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 Serves as a Biomarker of Heart Failure in the Salt-Sensitive Dahl Rat Model of Hypertension
Authors: Takaya Tomohide , Morimoto Tatsuya , Sunagawa Yoichi , Wada Hiromichi , Kawamura Teruhisa , Shimatsu Akira , Fujita Masatoshi , Fujita Yoshiko , Sawamura Tatsuya , Hasegawa Koji
Published: July 2021

Lectin-like oxidized low-density lipoprotein (LDL) receptor-1 (LOX-1) was originally identified as an endothelial receptor for oxidized LDL, and now is recognized as a multi-ligand receptor. LOX-1 expression in cardiomyocytes can be induced by oxidative stress and various hormonal stimuli. Activation of the LOX-1 pathway in cardiomyocytes induces apoptosis
in vitro
and deteriorates ischemia-reperfusion injury
in vivo
. However the role of LOX-1 in chronic heart failure is unknown. We examined the left ventricular (LV) expression of LOX-1 in a salt-sensitive Dahl (DS) rat model of hypertension. Compared with control salt-resistant Dahl (DR) rats, a high-salt diet, started at the age of 6 weeks, induced marked hypertension and apparent concentric LV hypertrophy on echocardiography in DS rats. The LV hypertrophy was moderate at the age of 11 weeks and marked at 18 weeks. The LV systolic function was preserved at 11 weeks, and decreased at 18 weeks. Quantitative real-time PCR revealed a 4.7-fold increase in LV levels of LOX-1 mRNA in DS rats compared with DR rats at 11 weeks, and a 32-fold increase at 18 weeks. The LV LOX-1 mRNA levels were significantly correlated with the LV end-systolic dimension (R=0.640, p=0.0002), and LV posterior wall thickness (R=0.555, p=0.0022), as well as the LV/body weight ratio (R=0.647, p=0.0002), and systolic blood pressure (R=0.751, p<0.0001). LOX-1 levels were also connected with an increase in LV mRNA levels of heme oxygenase-1 (R=0.692, p<0.0001), a marker of oxidative stress. Importantly, LOX-1 levels were strongly associated with a decrease in the LV ejection fraction (R=0.774, p<0.0001) and an increase in mRNA levels of BNP (R=0.814, p<0.0001), a representative marker of LV wall stress and heart failure. Immunohistochemistry demonstrated LOX-1 expression in cardiomyocytes as well as vessel walls of both DS and DR rat hearts. However, expression in cardiomyocytes was greater in DS than in DR. These findings demonstrate that LV cardiomyocyte expression of LOX-1 is markedly increased in proportion to the extent of heart failure and possibly involved in the deterioration of systolic function in the DS rat model of hypertension.
Abstract 843: Restrictive Cardiomyopathy Linked cTnI Mutation (K178E) Causes Severe Heart Failure and Early Mortality
Authors: Jean-Charles Pierre-Yves , Du Jianfeng , Li Yuejin , Gobara Nariman , Huang Xupei
Published: July 2021

Multiple mutations in cardiac troponin I (cTnI) have been linked to the development of restrictive cardiomyopathy (RCM) in human patients. Among them, K178E mutation has the worst clinical phenotype. K178E mutation may influence the inhibitory function through actin binding since previous studies have shown that amino acids number 173–181 bind to actin and increase the inhibitory effect of TnI. We modeled the mutation of lysine 178→glutamate (K178E) in human cTnI by cardiac specific expression of the mutated protein (cTnI
179Glu
in mouse sequence) in transgenic mice. Multiple lines were generated with varying degrees of expression to establish a dose relationship. Increased resting tension in isolated cardiac myocytes and decreased myofibrillar compliance were the main manifestations in cellular function measurements. In vivo cardiac function measured by high-resolution ultrasonic imaging and Doppler echocardiography revealed a significant diastolic dysfunction characterized with decrease of left ventricular end diastolic dimension (LVEDD), decreased cardiac ejection fraction (EF) and left ventricular faction of shortening (FS) as well as a decreased cardiac output (CO). Doppler measurements showed a restrictive left ventricular filling pattern, i.e. reversed E/A ratio; decreased deceleration time (DT); decreased isovolumic relaxation time (IVRT). Enlarged left and right atria was a dramatic sign, which was observed in most of the transgenic mice, and was developed early and fast (at age of 2–3 weeks). Severely affected lines developed a pathology similar to that observed in human restrictive cardiomyopathy patients who carry the same mutation and with a high early mortality. Our data indicate the causality of this mutation for diastolic dysfunction and heart failure and provide a useful animal model for further understanding the thin filament structure-function relationships and the physiological function of triponin in cardiac contraction and relaxation.

(Supported by NIH GM073621 and AHA0715116B)

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 860: Alteration In Blood Pressure Monitoring Technique Impacts Hypertension Treatment
Authors: Ray Gretchen M , Anderson Joe R , Nawarskas James J
Published: July 2021

Objectives
: Our study investigated the hypothesis that current methods of blood pressure (BP) assessment in an ambulatory clinic result in significantly different BP measurements than those obtained by following the American Heart Association (AHA) recommendations as well as the hypothesis that these BP differences result in treatment variation.

Methods:
This was a randomized, cross-over study in 40 patients with hypertension presenting to the UNMH Adult Internal Medicine Clinic. BP was measured in all patients in random order by the clinic staff using the traditional triage method and by the Principal Investigator using the AHA-recommended method. Trained observers documented BP techniques used. Two complete patient profiles were constructed for each patient one with the AHA BP and one with the triage BP. A panel of blinded providers including internists, a cardiologist, and a clinical pharmacist was asked to provide hypertensive treatment recommendations for each profile.

Results:
Only DBP differed significantly (77.6 mmHg ± 11.9 vs. 80.4 mmHg ± 10.5; p=0.02) between the triage and AHA methods, respectively. However, individual BP results varied greatly between the two methods. SBP readings differed by ≥5 mmHg in either direction for 68% of patients while 78% of patient’s DBP readings differed by ≥2 mmHg in either direction. Overall, 65% of patients were not at their goal BP when measured with the AHA method compared to 52% with the triage method (p<0.001). Multiple technical errors were seen during the triage method that likely accounted for the variation. Significant differences in treatment between profiles existed. The number of patients with treatment variations between their two profiles ranged from 13% to 23% (p<0.01 for all providers). Kappa scores indicated moderate to substantial clinical agreement between the physicians but only slight agreement between the pharmacist and physicians.

Conclusions:
When comparing the two methods of BP measurement, clinically significant differences were observed in a large percentage of patients. This difference significantly impacted hypertension treatment recommendations. Inaccurate BP assessment may lead to inappropriate treatment of hypertension.
Abstract 907: Plaque Burden at Left Main Coronary Artery of Patients Undergoing Percutaneous Coronary Intervention with Metabolic Syndrome
Authors: Miyagi Motohiro , Ishii Hideki , Amano Tetsuya , Uetani Tadayuki , Isobe Satoshi , Murakami Ryuichiro , Matsubara Tatsuaki , Murohara Toyoaki
Published: July 2021

Background:
The left main coronary artery (LMCA) is an important target of atherosclerotic plaque accumulation. The purpose of this study is to investigate the relationship between metabolic syndrome and plaque characteristics at LMCA.

Methods:
We enrolled 63 consecutive patients with stable angina who underwent percutaneous coronary intervention (PCI). Using intravascular ultrasound (IVUS), cross-sectional area (CSA), lumen area and plaque area were checked at LMCA undergoing PCI for the left anterior descending coronary artery or left circumflex coronary artery but not LMCA. Total plaque volume at LMCA was also checked by IVUS. The tissue characteristics of coronary plaque at LMCA was analyzed and quantified using integrated backscatter (IB) IVUS. The patients were devided into the two groups who had metabolic syndrome (n = 34) or not (n = 39). We evaluated the relationship between plaque burden at LMCA and metabolic syndrome.

Results:
Patients with metabolic syndrome had significantly larger plaque area and CSA at minimum lumen area (MLA) of LMCA than patients without metabolic syndrome (10.8 ± 3.7mm2 vs 8.2 ± 4.4 mm2, p = 0.01, 25.8 ± 5.0mm2 vs 23.1 ± 5.4 mm2, p = 0.04, respectively). About total plaque volume at LMCA, patients with metabolic syndrome had also significantly larger volume than patients without metabolic syndrome (53.8 ± 24.7mm3 vs 39.8 ± 21.2 mm3, p = 0.021, respectively). Furthermore, the lipid component of plaque volume at LMCA using IB-IVUS was significantly larger in patients with metabolic syndrome than without metabolic syndrome (25.7 ± 12.1mm3 vs 19.3 ± 11.6 mm3, p = 0.038, respectively).

Conclusion:
These findings suggest that patients with metabolic syndrome have not only larger plaque but also lipid-rich plaque at LMCA than without metabolic syndrome.
IVUS and IB-IVUS Parameter at LMCA
Abstract 951: Femoral Plaques Confound the Association of Circulating Oxidized Low-density Lipoprotein with Carotid Atherosclerosis in a General Population Aged 35–55 Years (Asklepios Study).
Authors: Rietzschel Ernst , Langlois Michel , De Buyzere Marc , De Bacquer Dirk , Bekaert Sofie , Blaton Victor , De Backer Guy , Gillebert Thierry
Published: July 2021

Objective. Previously reported associations of oxidized low-density lipoprotein (OxLDL) with non-invasive measures of atherosclerosis were inconsistent. Moreover oxLDL was not an independent predictor of future cardiovascular endpoints in models adjusting for lipid markers (total and HDL-cholesterol). Therefore, in the Asklepios Study cohort of 2524 asymptomatic subjects aged 35–55 years, we evaluated the multiple-adjusted association between circulating OxLDL and subclinical atherosclerosis in the carotid and femoral arteries (ultrasound based definitions).

Methods and results. Participants (mean age 45 years, 51.5% females) underwent a clinical examination, ultrasound protocol for determination of intima-media thickness (IMT) and plaques (Mannheim criteria) in the left and right carotid and femoral arteries, blood analysis for OxLDL (mAb-4E6) and other risk markers. They all completed a lifestyle variables study questionnaire. OxLDL concentrations were highest in subjects with femoral plaques (n=658). In the group of subjects with carotid plaques (n=476), elevated OxLDL concentrations were related to concomitant femoral plaques detected in 54% of these subjects. Stepwise multiple regression for oxLDL comprizing classical covariates demonstrated that non-HDL-cholesterol (beta 0.41), HDL-cholesterol (beta −0.34), femoral artery plaque (beta 8.97), ln(triglycerides) (beta 4.89), and gender (beta 2.79) were significant (p < 0.05) determinants. Full models including all appropriate anthropometric, hemodynamic, biochemical, and lifestyle variables confirmed that femoral plaques are independently related to OxLDL. Similar analyses demonstrated that femoral IMT, carotid IMT, or carotid plaques were not independently associated with OxLDL.

Conclusion. Circulating OxLDL is independently associated with femoral plaque and not with carotid artery wall damage.
Abstract 955: Vascular Function and Endothelial Progenitor Cells in Thromboangiitis Obliterans (Buerger’s Disease)
Authors: Nishioka Kenji , Higashi Yukihito , Umemura Takashi , Jituiki Daisuke , Goto Chikara , Nakamura Syuji , Hidaka Takayuki , Fujii Yuichi , Soga Jyunko , Hata Takaki , Idei Naomi , Fujimura Noritaka , Teragawa Hiroki , Kihara Yasuki
Published: July 2021

Background: Buerger’s disease is associated with endothelial dysfunction. Several lines of evidence have shown that the circulating number and function of endothelial progenitor cells (EPCs) are surrogate biologic markers for cardiovascular diseases.

Methods and Results: The purpose of this study was to evaluate the role of EPCs in endothelial function in Buerger’s disease. We measured flow-mediated vasodilation (FMD), nitroglycerine (NTG)-induced vasodilation, circulating levels of EPCs, cell migration response to vascular endothelial growth factor (VEGF), and serum levels of VEGF in 25 patients with Buerger’s disease and 25 age- and sex-matched healthy subjects, and 25 patients with atherosclerosis obliterans (ASO). Vascular reactivity of brachial artery was measured by using high-resolution ultrasound. Circulating EPCs were quantified by flow cytometry. Cell migration assay was performed by the Boyden chamber technique. FMD was lower in both the Buerger’s group and the ASO group than in the control group (Buerger; 6.6±3.1%, ASO; 5.5±5.4%, vs. control; 10.6±3.3%, p<0.01, respectively). There was no significant difference in FMD between the Buerger’s group and ASO group. The number of circulating EPCs was similar in the Buerger’s group and control group, whereas the number of circulating EPCs was lower in the ASO group than in other groups (Buerger; 966±543/mL; control; 980±424/mL, vs. ASO; 466±339/mL, p<0.01, respectively). Cell migration to VEGF was similar in the Buerger’s group and control group, whereas cell migration was lower in the ASO group than in other groups (Buerger; 12.8±4.1/hpf; control; 13.2±3.5/hpf, vs. ASO; 4.2±1.1/hpf, p<0.01, respectively). Serum VEGF levels was higher in the Buerger’s and ASO groups than in the control group, whereas serum VEGF levels was similar in the Buerger’s group and ASO group.

Conclusions: These findings suggest that FMD was impaired in patient with Burger’s disease as well as patients with ASO compared with normal control subjects and that the number and function of EPCs were not decreased in patients with Burger’s disease. EPCs may be mobilized to restore endothelial function in Buerger’s disease. In patients with ASO, both the mobilizations of EPCs and endothelial function were impaired.