bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 3104: Heart Rate Recovery Predicts Major Cardiac Events in Patients with Heart Failure Receiving a Beta-Blocking Agent
Authors: Arena Ross , Myers Jonathan , Peberdy Mary Ann , Bensimhon Daniel , Abella Joshua , Chase Paul , Guazzi Marco
Published: July 2021

Introduction:
Heart rate recovery (HRR) following a maximal exercise test has demonstrated prognostic value in several investigations. The analysis of HRR in the heart failure (HF) population is, however, limited, particularly in a cohort receiving a beta-blocking (BB) agent.

Hypothesis:
We assessed the hypothesis that HRR would maintain prognostic value in HF patients prescribed a BB agent.

Methods:
One hundred and fifty-one subjects with HF (79% male/21% female, 54% ischemic/ 46% non-ischemic, age: 54.3 ± 12.6 years, ejection fraction: 31.2 ± 15.3%), on a stable dose of a BB agent, underwent cardiopulmonary exercise testing to determine peak oxygen consumption (VO
2
), the minute ventilation/carbon dioxide production (VE/VCO
2
) slope, peak respiratory exchange ratio (RER), percent-predicted maximal heart rate achieved (PPMHR) and HRR at one minute. Subjects were tracked for major cardiac events following testing.

Results:
Mean values for peak VO
2
, the VE/VCO
2
slope, peak RER, PPMHR and HRR were 17.9 ± 6.8 mlO
2
·kg
−1
·min
−1
, 33.0 ± 8.7, 1.07 ± 0.14, 75.1 ± 14.9% and 16.4 ± 13.6 beats per minute, respectively. There were 25 major cardiac events (20 deaths, 2 transplants, 3 left ventricular assist device implantations; mean tracking period: 26.7 ± 23.2 months, annual event rate: 6.8%) during the tracking period. A HRR threshold of ≤/> 11 beats per minute was prognostically optimal (hazard ratio: 4.4, 95% confidence interval: 1.8 –10.6, 91.1% vs. 72.1% event free survival, p<0.001). Multivariate Cox regression analysis revealed the VE/VCO
2
slope was the strongest predictor of cardiac events (Chi-square: 13.7, p<0.001) while HRR added significant value and was retained (residual chi-square: 4.6, p = 0.03). Peak VO
2
did not add prognostic value and was removed from the regression (residual chi-square: 0.97, p = 0.33).

Conclusions:
In conclusion, these results indicate HRR maintains prognostic value in HF patients prescribed a BB agent. Furthermore, HRR added predictive value to the VE/VCO
2
slope, perhaps one of the strongest prognostic markers obtained from cardiopulmonary exercise testing. The clinical assessment of HRR may therefore be warranted in HF patients who are prescribed a BB agent.
Abstract 3107: Arm Exercise Stress Testing Variables Predict Survival and Adverse Clinical Outcomes
Authors: Ilias Nasreen , Hong Xian , Inman Cindi , Martin Wade
Published: July 2021

Valuable prognostic and clinical information from treadmill exercise testing (GXT) includes exercise capacity (METs), heart rate, and electrocardiographic (ECG) responses. However, little or no prognostic data are available for arm ergometer stress testing (AXT). To determine whether AXT variables predict survival, myocardial infarction (MI), or coronary revascularization (CVASC), we performed AXT from 1997 to 2002 in 359 patients, mean age 63 +/− 11 (SD) years, referred for clinical reasons but unable to perform GXT, and followed for 63 +/− 24 months, during which 98 deaths occurred (27%). Average annual mortality, MI, CVASC, and combined adverse event rates were 5.2%, 1.7%, 2.2%, and 7.1%, respectively. Student’s t-tests were used to assess differences between outcome groups. Cox regression models were employed to determine hazard ratios (HR) and 95% confidence intervals (CI). Kaplan-Meier survival models were used to compare survival curves among AXT groups. AXT METs was highly predictive of survival after adjustment for age and beta blocker treatment (p < 0.001; when stratified by tertiles; death HR 0.47, CI 0.22– 0.71 middle vs. lowest; HR 0.61, CI 0.28 – 0.94 highest vs. middle). A greater delta (peak-rest) heart rate was associated with survival (p = 0.0003) and/or event-free outcome as were faster % age-predicted peak heart rate (death HR 0.58, CI 0.36 – 0.80 for >70% vs.> 70%), higher exercise systolic blood pressure (SBP) (p = 0.002) and peak heart rate x SBP product (PRPP) (p = 0.0006). A positive (+) AXT ECG was observed in 22% of deaths and 10% of survivors, 27% of MI and 12% with no MI, and 32% of CVASC versus 11% with no CVASC. A+AXT ECG was a powerful predictor of adverse outcome, even after accounting for peak heart rate, peak SBP and PRPP (death HR 2.2, CI 1.94 –2.43; MI HR 2.9, CI 2.48 –3.30; CVASC HR 4.1, CI 3.73– 4.43; combined events HR 2.8, CI 2.55–2.98). Sensitivity, specificity, positive and negative predictive values of a +AXT ECG in prognosticating adverse outcomes ranged from 22–31%, 88 –92%, 18 – 61%, and 62–92%, respectively. Thus, in veterans who are older and have more comorbidities than most other study populations based on adverse event rates, AXT is an alternative to GXT for predicting clinical outcome in patients with lower extremity disabilities.
Abstract 429: The Failing Senescent Heart Contains a Pool of Functionally Competent Progenitor Cells
Authors: Gonzalez Arantxa , Rota Marcello , Nurzynska Daria , Misao Yu , Tillmanns Jochen , Ojaimi Caroline , Padin-Iruegas Elena , Mueller Patrick , Esposito Grazia , Bearzi Claudia , Vitale Serena , Dawn Buddhadeb , Baker Mathue , Hintze Thomas H , Bolli Roberto , Urbanek Konrad , Hosoda Toru , Kajstura Jan , Anversa Piero , Leri Annarosa
Published: July 2021

A critical question concerns whether myocardial aging affects uniformly all cardiac progenitor cells (CPCs) or a subset of functionally competent CPCs persists in the senescent heart suggesting that these cells may be activated to form new contracting myocardium. CPCs isolated from the heart of rats at 3, 12, 16 and 24 months were found to express IGF-1-IGF-1R, HGF-c-Met and the components of the renin-angiotensin system (RAS). Although mRNA for angiotensinogen and AT1-receptors decreased in old CPCs, the quantity of these proteins did not vary with aging. Renin mRNA increased at 12 and 16 months and returned to baseline at 24 months. Additionally, Ang II synthesis was 3-fold higher in old than in young CPCs and this difference persisted after ligand activation. Conversely, a decrease in IGF-1R, IGF-1 and HGF mRNA, and IGF-1R and c-Met proteins occurred in old CPCs. Baseline values for IGF-1 secretion were similar in young and old CPCs, but in response to ligand stimulation IGF-1 synthesis was 8-fold higher in young CPCs. HGF did not vary. Collectively, these results indicate that aging led to an increase in RAS function and a decrease in IGF-1-IGF-1R and HGF-c-Met function in CPCs. However, whether these aging effects involved the entire CPC pool remained unknown. Based on the expression of the senescence-associated protein p16
INK4a
and telomere length, CPCs in the old heart consisted of two subsets: a large compartment of p16
INK4a
-positive CPCs with short telomeres and a small pool of p16
INK4a
-negative CPCs with long telomeres. CPCs expressing IGF-1-IGF-1R and HGF-c-Met were consistently negative for p16
INK4a
while p16
INK4a
was detected in CPCs positive for Ang II and AT1-receptors. Therefore, the ability of IGF-1 and HGF to induce CPC proliferation was attenuated but not abolished in old CPCs which also showed a modest 29% decrease in telomerase activity. Ang II stimulated apoptosis in both young and old CPCs but oxidative DNA damage was higher in old cells. Studies in vivo were then performed documenting that CPCs can be activated in the old heart by the local injection of growth factors. By this strategy, the senescent heart phenotype was partially corrected and the improvement in cardiac hemodynamics resulted in prolongation of maximum lifespan.
Abstract 3137: Long-term Outcomes Following Sirolimus-Eluting Stent Implantation for Off Label Indications
Authors: Cosgrave John , Aranzulla Tiziana Claudia , Qasim Asif , Latib Azeem Mohamed , Melzi Gloria , Airoldi Flavio , Chieffo Alaide , Sangiorgi Giuseppe Massimo , Montorfano Matteo , Michev Iassen , Carlino Mauro , Colombo Antonio
Published: July 2021

Introduction:
Only limited long term data exist following SES implantation and these primarily come from the randomized trials which enrolled highly selected patients. Due to the risk of stent thrombosis long term safety concerns exist particularly following off label SES implantation.

Hypothesis:
Off label implantation of SES has a favorable long term safety profile.

Methods:
All consecutive patients successfully treated with SES prior to March 2003 were considered for analysis. The endpoints analyzed were MACE, death, myocardial infarction (MI), target vessel revascularization (TVR) and target lesion revascularization (TLR) and late stent thrombosis. We considered the following as off-label indications: ostial lesions, chronic total occlusions, bifurcations, left main stem lesions, saphenous vein grafts, internal mammary artery, ejection fraction < 30 %, restenotic lesions.

Results:
Our cohort comprised 445 patients with 954 lesions. At least one off label indication was present in 322 (72%) of patients and 161 (36.2%) had more than 1 off label indication (Table

). Median clinical follow-up was 4.4 years and 78% of patients had at least 4 years of follow-up. There was a trend towards a higher MACE rate in the off-label group due in the main to a significantly higher repeat revascularization rate. There were no differences in the incidence of death or myocardial infarction. The overall rate of late thrombosis was similar to that seen in the literature (1–2%) and while there was a slightly higher number in the off-label group this did not reach statistical significance.

Conclusions:
In our experience off label implantation of SES is associated with higher MACE rates due to the increased need for repeat revascularization. This can be explained by the complexity of this cohort with a large number of lesion types not included in randomized trials. Of note long term safety is acceptable with no difference in death or MI when compared to on-label indications.

Follow-up clinical events in the two groups
Abstract 3143: Reverse Hemodynamic Remodelling May Be Possible Over Time
Authors: Stevenson Lynne W , Cho Yong K , Heywood J. T , Bourge Robert C , Abraham William T , Manda Ven , O’Connor Christopher M
Published: July 2021

Introduction
: Elevated filling pressures are a hallmark of chronic heart failure. They can be reduced acutely during HF hospitalization but the hemodynamic impact of ongoing therapy to maintain optivolemia has not been established.

Methods and Results
: After recent HF hospitalization, 274 NYHA Class III or IV HF patients were enrolled in the COMPASS-HF study at 28 experienced HF centers and received intense HF management (average 24.7 staff contacts/ 6 months) ± access to filling pressure information to adjust diuretics to maintain optivolemia, usually defined as estimated pulmonary artery diastolic (PAD) pressure of 12±4 mmHg. Filling pressure information was available for half the patients during the first 6 months (the Chronicle group, <Access), and for all patients during the next 6 months. Diuretics were adjusted 12.7 times per patient in the Chronicle group and 8.2 times per patient in the Control (-Access) group during the first 6 months (p = 0.0001). Compared to baseline, decreases in RV systolic pressure (RVSP) and ePAD were significant for the +Access patients by one year (p=0.0012 and p =.04, respectively). The Control patients exhibited a similar trend 6 months after crossing to +Access (figure

).

Conclusions:
Targeted therapeutic adjustments, based on continuous filling pressures along with intensification of HF management contacts, are associated with a reduction in chronic left-sided filling pressures and right ventricular load.
Abstract 3145: Mortal Interaction of Sleep Apnea with Ischemic, But Not Non-Ischemic Heart Failure
Authors: Yumino Dai , Wang Hanqiao , Newton Gary E , Mak Susanna , Paker John D , Floras John S , Bradley T D
Published: July 2021

Introduction:
Past studies showed that in patients with heart failure (HF), sleep apnea (SA) increases mortality risk, but these patients were not characterized on the basis of HF etiology.

Hypothesis:
Since patients with ischemic HF may suffer greater adverse consequences of SA-related hypoxia and hypertension than those with non-ischemic HF, SA will increase risk of death in patients with ischemic, but not in those with non-ischemic HF.

Methods:
From 1997 to 2004, consecutive HF patients with ejection fraction (EF) ≤ 45% had sleep studies and were divided into those with SA (apnea-hypopnea index ≥ 15/hr of sleep) and those without SA. They were followed prospectively to determine all-cause mortality rate.

Results:
Of 218 patients enrolled, follow up data were obtained in 95%. Of these, 87 (40%) had ischemic HF. SA was found in 53% of those with ischemic HF and in 41% of those with non-ischemic HF. 14 patients with obstructive sleep apnea on CPAP therapy were excluded from the analysis. Of the remaining 193 patients, 34 (18%) died during a mean follow up of 32 months. In the non-ischemic HF group, there was no difference in mortality between those with, and those without SA (Figure

). In contrast, in the ischemic group, mortality was significantly higher in those with SA than those without it (18.9 vs. 4.6 deaths/100 patient-years, P = 0.003). After adjusting for age, EF, New York Heart Association class, β-blocker use, and the presence of diabetes using multivariate Cox analysis, SA remained a significant independent risk for death (HR 3.02, 95%CI 1.07– 8.59, P = 0.037).

Conclusions:
These data show that ischemic etiology identifies those HF patients with SA at increased risk of death.
Abstract 3149: Greater Fluid Retention is Associated with Increased Cardiovascular Death Risk in 34,003 CKD Patients on Hemodialysis
Authors: Kalantar-Zadeh Kamyar , Bunnapradist Suphamai , Regidor Deborah L , Streja Elani , McAllister Charles J , Horwich Tamara B , Fonarow Gregg C
Published: July 2021

Background:
Patients with chronic kidney disease (CKD) stage 5 who undergo hemodialysis (HD) treatment have striking similarities to heart failure (HF) patients, in that both populations retain fluid frequently, have excessively high mortality, and exhibit an obesity paradox. We hypothesized that in HD patients greater interdialytic fluid retention is associated with poor cardiovascular (CV) survival.

Methods:
We examined the 2-year (7/2001– 6/2003) CV mortality in 34,003 HD patients across the United States, who had an averaged weight gain of at least 0.5 kg above their end-dialysis dry weight by the time the subsequent HD treatment started. The 3-month averaged interdialytic weight gain was divided into 8 categories of 0.5 kg increments (up to >= 4.0 kg).

Results
: In unadjusted analyses, higher weight gains were associated with better nutritional status (higher protein intake, serum albumin and body mass index) and tended to be linked to greater survival. However after multivariate adjustment for demographics (case-mix) and also surrogates of malnutrition-inflammation-cachexia syndrome (MICS), higher weight gain increments were associated with increased CV death risk. [Figure

]

Conclusions:
In HD patients greater fluid retention between two subsequent HD treatment sessions is associated with higher CV death risk. The mechanisms by which fluid retention influences survival in HD may be similar to HF patients and warrants further research.
Abstract 3154: Interacton of Left Ventricular Geometry and Cardiovascular Hemodynamics in 57,307 Patients wth Preserved Ejection Fraction
Authors: Milani Richard V , Lavie Carl J
Published: July 2021

We and others have demonstrated the prognostic impact of LV geometry on subsequent survival in patients with preserved ejection. The purpose of this investigation was to describe parameters of cardiovascular hemodynamics and energetics associated with normal and abnormal LV geometry, including concentric remodeling (CR), eccentric hypertrophy (EH), and concentric hypertrophy (CH) fraction in patients who were referred for routine echocardiographic evaluation. Measures were obtained using standard non-invasive methods previously reported. Survival was obtained by the National Death Index after a mean follow-up of 2.8 years.

Conclusion:
Changes in LV geometry are associated with significant abnormalities in cardiac and vascular hemodynamics and energetics that in general progress from CR to frank hypertrophy. Intervention directed towards modifying these parameters are needed in order to evaluate the potential for improving clinical outcomes.
Abstract 433: HDAC7 is Essential for Stem Cell Differentiation into Smooth Muscle Cells
Authors: Margariti Andriana , Xiao Qingzhong , Zampetaki Anna , Hu Yanhua , Zeng Lingfang , Xu Qingbo
Published: July 2021

Background: Embryonic stem cells (ESCs) possess the potential to differentiate into specific cell lineages, such as vascular smooth muscle cells (SMCs). The homeostasis of histone acetylation and deacetylation mediated by histone deacetylase (HDAC) is known to play a central role in the regulation of gene expression, through co-operation with other transcription factors. However, it is unknown whether HDAC plays a role in mediating stem cell differentiation into SMCs.

Methods and results: Mouse ESCs were seeded on collagen IV-coated flasks and cultured in the absence of Leukemia Inhibitory Factor (LIF) in differentiation medium for 3 to 9 days in order to induce SMCs differentiation. Western blots and double-immunofluorescence staining demonstrated that HDAC7 expressed in parallel with SMC marker genes. Upregulation of HDAC7 expression resulted in increase in SMC marker expression, while downregulation of HDAC7 by siRNA caused decrease of SMC marker expression. In ex vivo culture of embryonic cells from SM22-LacZ transgenic mice, over-expression of HDAC7 significantly increased beta-gal positive cells, indicating a crucial role of HDAC7 in SMC differentiation during embryonic development. An important observation of this study is that HDAC7 undergoes alternative splicing during ESC differentiation, resulting in alternative translation from second ATG codon, giving rise to a short HDAC7 missing the N-terminal 22 amino acids. We also found that PDGF induced SMCs differentiation through the regulation of HDAC7 transcription and splicing, in which siHDAC7 knockdown ablated PDGF-induced SMC marker expression. Spliced HDAC7 increased SMC differentiation, while the short HDAC7 had no effect or even downregulated SMC differentiation. Further experiments revealed that the short HDAC7 isoform bound to MEF2C, while the full length HDAC7 did not, indicating that HDAC7 splicing can induce SMCs differentiation through the modulation of MEF2C-mediated gene expression.

Conclusions: Our findings provide novel information on the mechanism involved in SMC differentiation, and identify HDAC7 as a new target in therapeutic intervention on vascular disease, where inhibition of vascular progenitor cell differentiation into SMCs would be beneficial.
Abstract 3195: Quantification of Endothelial Cell Apoptosis in Pulmonary Arterial Hypertension Using Tc99m-Annexin V
Authors: Rattigan Eileen M , Sedlar Marija , DelGiacco Elizabeth , Okajima Kazue , Hoppin John , Johnson Lynne L
Published: July 2021

Background
- Pulmonary artery hypertension (PAH) is usually detected late in its course. Early detection may allow for the earlier initiation of disease-modifying therapies. Endothelial cell (EC) apoptosis is an early event that leads to unrestrained EC growth and subsequent smooth muscle cell proliferation. We tested the hypothesis that these early apoptotic changes may be detected non-invasively using Tc99m-labeled Annexin V (Tc99m-ANX) in the monocrotaline (MCT)-induced PAH rat model.

Methods
- To document disease course, 54 MCT treated Sprague Dawley rats (60mg/kg) were compared to 18 controls; 5– 6 treated rats and 3 controls were sacrificed weekly over 6 weeks for gross pathology and histopathologic sectioning. PA pressures were estimated by echocardiography. EC apoptosis was detected by caspase staining in arterioles smaller than 50 microns and quantified by random sampling. A second group of 16 rats were treated with MCT and underwent serial non-invasive SPECT imaging. They were injected with 55.5 MBq of Tc99m-ANX and imaged by HiSPECT at baseline (before MCT) and weekly for 6 weeks. Quantification of Tc99m-ANX uptake was assessed by biodistribution and by region of interest (ROI) analyses of SPECT images using MIP Tool.

Results
- See table

below. Quantitative pulmonary tracer uptake peaked at day 14, correlated with peak positive caspase staining and preceded hemodynamic changes and RVH. Tc99m-ANX pulmonary uptake seen at later time points corresponded to caspase positive inflammatory cells in a dense intra-alveolar infiltrate.

Conclusions
- EC apoptosis can be detected in vivo with Tc99m-ANX during the early development of PAH in MCT treated rats before the onset of any detectable changes in pulmonary pressures or changes in RV architecture.

Data Summary
Abstract 437: Bmper Regualtes Bmp Signaling Through Endocytosis
Authors: Kelley Russell , Ren Rongqin , Ross Malcolm , Pi Xinchun , Wu Yaxu , Patterson Cam
Published: July 2021

Signaling through Bone Morphogenic Proteins (Bmp) governs the patterning of many tissues including the cardiovascular system. Nevertheless, simple models of Bmp regulation are insufficient to explain the divergent and tightly regulated roles of Bmp signaling in development and disease. Bone Morphogenic Protein binding Endothelial cell precursor Regulator (Bmper; Cv2 or crossveinless 2) is a secreted factor that regulates Bmp activity in a tissue- and stage-dependent manner. Pro- and anti-Bmp activities have been postulated for extracellular Bmper, although the molecular mechanisms through which Bmper affects Bmp signaling are unclear. We show here that as molar concentration increases, Bmper dynamically switches from a Bmp4 agonist to one that antagonizes Bmp4-mediated Smad activation. Rather than strictly acting in the extracellular compartment, a molar excess of Bmper to Bmp4 leads to their internalization through an endosomal pathway fated for lysosomal degradation. This Bmp trap and sink mechanism is clathrin-mediated and is dependent on the degree of Bmper proteolysis. Bmper-mediated internalization of Bmp4 reduces the duration and magnitude of Bmp4-dependent Smad and MAPK activation and pursuant Bmp-responsive gene transcription in embryonic mesenchyme. As observed in model systems of Bmp signaling, our data indicate that control of sensitivity to Bmp signaling occurs through a complex interplay between Bmper and Chordin. Our observations support a dramatic reconstitution of the existing paradigm for understanding Bmp signaling, one that extends the extracellular activity of selective Bmp modulators to include subcellular regulation. A concentration-dependent molecular switch resolves critical discordances through which Bmper regulates Bmp activity, and has broad implications for Bmp signaling in vivo.
Abstract 3210: Early Invasive Management of Acute Coronary Syndromes without ST-elevation does not Improve Long-term Mortality: insights from the Randomized Trials with the most Recent Follow-up Data
Authors: Verheugt Freek W , Brouwer Marc A
Published: July 2021

Background

Randomized trials evaluating an early invasive against a conservative strategy show a benefit over a conservative approach in the composite of death, MI and revascularisation/recurrent ischemia. However, by the necessarily open design MI and revascularisation/ recurrent ischemia are relatively weak endpoints. Since MI is both an entry criterion and an endpoint, it is difficult to evaluate, since it may be induced by intervention and, therefore, its definition in the trials is cumbersome. Thus, long-term mortality is the best outcome parameter to evaluate the above strategies. Recently, the very long follow-up data of 3 major trials RITA-3, FRISC-2 and ICTUS have been published.

Methods and Results

We analyzed the 9 trials carried out between 1996 and 2004, which randomized 10,558 patients with non-ST-elevation acute coronary syndromes to an early invasive or an ischemia-guided conservative strategy. F/U ranged from 6 months to 5 years with a total of 30,932 patients-years. RR for long-term mortality is for invasive versus conservative from completed follow-up data is 0.94 (95%CI 0.83–1.06, p = 0.32, see figure

).

Conclusion

Although most trials on non ST-elevation ACS reported a reduction in the composite of death, MI and revascularisation/recurrent ischemia, an early invasive strategy does not lead to improved survival on the very long-term. These findings should be mentioned in future guidelines.
Abstract 3218: Pharmacokinetics, Pharmacodynamics, and Safety of an Anti-von Willebrand Factor Therapeutic Aptamer, ARC1779, in Healthy Volunteers
Authors: Gilbert James C , DeFeo-Fraulini Tia , Hutabarat Renta M , Horvath Christopher J , Merlino Patricia G , Marsh H N , Healy Judy M , Fahkreddine Sleiman B , Holohan Thomas V , Schaub Robert
Published: July 2021

Background: The prominent role played by vWF in arterial thrombogenesis suggests that vWF inhibition may offer an effective adjunct therapy to PCI in ACS patients. ARC1779 is a PEG-conjugated aptamer that blocks platelet activation through inhibition of vWF A1 domain binding to platelet receptor GPIb. Design: This was an ascending-dose, double-blind, placebo-controlled study in 47 healthy volunteers at doses of 0 (placebo, n = 6) or 0.05 to 1.0 mg/kg ARC1779 (n = 41) given via IV push, “slow bolus” IV infusion over 15 minutes, or “slow bolus” followed by 4-hour IV infusion. PK parameters were estimated from plasma ARC1779 concentrations determined with a validated assay. PD effects were measured by an ELISA for free vWF A1 binding sites and by a platelet function analyzer, the PFA-100
®
. PK: The concentration-time profiles for ARC1779 after IV push or slow bolus appeared monophasic, though the terminal phase may not have been fully captured. The C
max
and AUC values were dose-proportional. The highest exposure was observed after 1.0 mg/kg slow bolus, with mean C
max
of 21.15 μg/mL and AUC
(0-∞)
of 80.92 μ g·hr/mL. The mean apparent elimination half-life (t
1/2β
) was ~2 hours and mean residence time (MRT) was ~3 hours. The mean apparent volumes of distribution (V
z
and V
ss
) were ~1/2 of the blood volume, suggesting that ARC1779 distribution is in the central compartment. The mean clearance (CL) values ranged from ~10% to 21% of GRF, suggesting that renal filtration may not be a major mechanism of clearance of ARC1779. PD: Inhibition of vWF A1 binding was achieved in a dose- and concentration-dependent manner, with respective EC
50
and EC
90
values of 0.22 μ g/mL (17 nM) and 1.98 μg/mL (151 nM). Platelet function inhibition (PFA-100
®
closure time) was achieved, with respective EC
50
and EC
90
values of 0.75 μ g/mL (57 nM) and 2.57 μg/mL (196 nM). vWF activity returned in a dose- and concentration-dependent manner. Safety: ARC1779 was generally well tolerated and no bleeding was observed. Adverse events tended to be minor and not dose related. One volunteer had a hypersensitivity reaction to IV push administration, but no such reactions occurred at higher doses given by slow bolus or infusion.

Conclusion: The PK, PD and safety profile of ARC1779 supports its therapeutic potential for use in ACS.
Abstract 3221: Impact of Thienopyridines on Re-Operation Rates, Bleeding Outcomes and Hospitalization in ACS Patients Requiring CABG Surgery
Authors: Berger Jeffrey S , Frye Carla B , Harshaw Qing , Edwards Fred H , Steinhubl Steven R , Becker Richard C
Published: July 2021

Objective:
The objective of this retrospective observational study is to examine the impact of preoperative administration of clopidogrel on re-operation rates, incidence of life-threatening bleeding, inpatient length of stay (LOS) and other bleeding-related outcomes in ACS patients requiring CABG in a broad cross-section of US hospitals.
This is the first study designed with this objective to be conducted in multiple centers
.

Methods:
A retrospective cohort analysis of ACS patients requiring CABG surgery during their index hospitalization was completed. Each site randomly selected 40–50 cases divided into the two comparison groups which consisted of patients exposed to clopidogrel versus those not exposed to clopidogrel within 5 days prior to surgery.

Results:
Data from the first 361 patients in 12 hospitals are reported. The two groups were comparable at baseline in terms of age, gender and co-morbidities. The rate of re-operation in the exposed group was 6.3% vs. 1.5% (p = 0.016) in those not exposed within 5 days. The number of patients who experienced excessive or life-threatening bleeding was higher in the exposed group; total inpatient LOS was not significantly different. Patients in the exposed group also required more blood product transfusions.

Relationship between Clopidogrel Exposure and LOS, Markers for Life Threatening Bleeding, and Reoperation - Interim Analysis, 12 sites reporting

Conclusion:
Exposure to clopidogrel within 5 days before CABG surgery in ACS patients appears to significantly increase the need for re-operation and major bleeding outcomes in a broad cross-section of hospitals.
Abstract 3225: Ablation Of The Pulmonary Veins Using An Irrigated Tip Rf Ablation Catheter Reduces Cerebral Microemboli Versus A Non-irrigated-tip Rf Ablation Catheter.
Authors: Sauren Loes , De Roy Luc , Pison Laurent , la Meir Mark , van der Veen Erik , Mess Werner , Crijns Harry , Maessen Jos
Published: July 2021

Background
Pulmonary vein isolation (PVI) has become an established treatment for patients with atrial fibrillation (AF). But post-intervention complications like, TIA, stroke and cognitive decline, might occur. In this study the incidence of microembolic signals (MES) was determined during percutaneous PVI; non-irrigated tip radiofrequency (RF) ablation versus irrigated tip RF ablation.

Methods and Results
Twelve patients underwent PV catheter RF ablation. Two patient groups were selected; Group NON-IRRIGATED RF: a non-irrigated RF ablation catheter (temperature< 55°, power< 30 W) was used in 7 patients, Group IRRIGATED RF: an irrigated tip RF ablation catheter (temperature< 43°, power< 25 W) was used in 5 patients. Transcranial Doppler (TCD) was used to detect microembolic signals in the middle cerebral arteries. The duration of the procedure, the number of applications and the total ablation time was not different between both groups. In the IRRIGATED RF group versus the NON-IRRIGATED group less cerebral MES were detected during the complete procedure (1570 vs. 3515) and per 1 minute of ablation (4 vs.89).

Conclusions
Ablation of the pulmonary veins in a percutaneous endocardial approach causes a significant number of cerebral MES during the procedure. The cerebral MES detected during ablation are most likely gas bubbles and solid emboli due to overheating of the tissue and blood. Because a positive association between the number of cerebral MES and the risk of stroke and neurological impairment has been reported, the RF irrigated tip ablation catheter might be preferable in an effort to reduce the stroke risk.

Number of MES during irrigated and non-irrigated PVI
Abstract 3234: Patterns of Treatment of Patients with Atrial Fibrillation
Authors: Prudente Liza A , Mangrum J. Michael , Lake Douglas E , Xiao Yuping , DiMarco John P , Mahapatra Srijoy , Ferguson John D , Moorman J. Randall , Mounsey J. Paul
Published: July 2021

Background:
Atrial fibrillation (AF) is increasingly common, and a number of treatment options are available. Since trials such as AFFIRM show no mortality difference between rate or rhythm control strategies, we hypothesized that rate control would become more common with increased duration of AF.

Methods:
We evaluated history of treatment modalities in 1052 patients with AF referred to a dedicated AF center. 472 had AF for ≥ 5 years and 200 for ≥ 10 years. We recorded AF symptom burden, calculated as the product of frequency and duration of episodes, and treatment history from first AF episode using a database modeled on AHA-recommended key data elements.

Results:
The median (25th, 75th percentiles) AF duration was 4.5 (2, 9) years. The median symptom burden was 28% in the first year after symptoms started, and fluctuated from 10 to 15% thereafter. 37% had a CHADS2 score 0, 43% had score 1, and 20% had score ≥ 2. Anti-thrombotic use was near 40%. The Figure

shows the spectrum of drug use. In the first year, rate control drugs (blue bars) were used 2.5 fold more commonly than AAD.
Surprisingly, the use of anti-arrhythmic drugs (AAD) increased with duration of AF
and after five years, they were nearly equal. 20% of patients had cardioversion in the first year, 3% in the second, and 1% or less for year 5 and after. 60% of all cardioversions were performed in the first year of symptoms.

Conclusion:
Cardioversion is more common during the first year of AF. In subsequent years, symptom burden falls and is relatively stable. AAD usage increases while rate control use remains constant. This suggests that physicians may continue to use AAD drugs to help control symptoms.
Abstract 3259: Intra-Aortic Balloon Pump Insertion Prior to LVAD Implantation Improves Short-term Survival in High-Risk LVAD Recipients
Authors: Naseem Tariq M , Comas George M , Mangi Abeel A , Martens Timothy P , Cheema Faisal H , Arif Hiba , Bialo Darren A , Khalid Imran , Argenziano Michael , Naka Yoshifumi
Published: July 2021

INTRODUCTION: Intra-aortic balloon pump (IABP) insertion can augment cardiac function in the setting of acutely decompensated heart failure. The aim of this study was to determine if IABP insertion prior to left ventricular assist device (LVAD) implantation improves outcomes in LVAD recipients.

HYPOTHESIS: We assessed the hypothesis that pre-operative IABP insertion for hemodynamic stability and improved organ perfusion would lead to better outcomes post-LVAD implant

METHODS: We have previously described a preoperative LVAD risk score (LRS), which is based on preoperative characteristics associated with inferior outcomes after LVAD insertion (e.g. previous cardiac surgery, ventilator dependence, elevated central venous pressure, elevated prothrombin time). We retrospectively reviewed the records of 245 patients undergoing LVAD implantation (Heartmate I, Heartmate II & DeBakey) at our center between 1996 and 2006, including preoperative LRS and 30-day survival. Patients were categorized as those who received an IABP prior to LVAD implant for hemodynamic stability and those who did not. Data were analyzed by Chi-square and Mann-Whitney U tests.

RESULTS: Of 245 patients having LVAD implants during the study period, 174 (71%) had a LRS of 1–5 (low-risk group), while 71 (29%) had a LRS of 6 –10 (high-risk group). A total of 95 patients received an IABP prior to LVAD insertion during this period: 54 (31%) of the low-risk patients and 41 (58%) of the high-risk patients. In the high-risk cohort, patients receiving pre-operative IABP (n = 41) had superior 30-day survival compared with patients who did not receive an IABP (n = 30) (78% vs. 57%, p < 0.05). Conversely, in the low-risk group, IABP insertion was associated with a trend toward lower 30-day survival (78% vs. 92%, p < 0.1). In the low-risk group, the rate of successful bridging to transplantation was higher in patients who did not receive pre-operative IABP support (86% vs. 69%, p < 0.01).

CONCLUSION: LVAD candidates with a high LVAD risk score, a preoperative surrogate of increased perioperative risk, have improved 30-day survival if stabilized with an IABP prior to LVAD implantation.
Abstract 3264: Changes in left and right ventricular structure and function of donor hearts during the first year after heart transplantation using Tissue Doppler Imaging and Myocardial Performance Index
Authors: Goland Sorel , Czer Lawrence S , Siegel Robert J , Burton Kevin , Naqvi Tasneem Z , Zivari Kaveh , Rafique Asim , De Robertis Michele A , Luthringer Daniel , Schwarz Ernst , Kass Robert M , Trento Alfredo
Published: July 2021

Objectives:
Normal changes in Tissue Doppler imaging (TDI) velocities and myocardial performance index (MPI) after heart transplantation (HTx) have not been evaluated.

Aim:
To assess left and right ventricular (LV and RV) structure and function during the 1st year after HTx using TDI and MPI.

Methods.
20 donors (mean age 35 ± 13, 20 M) had baseline echocardiogram (echo) and 20 recipients (mean age 59 ± 9, 14 M) underwent serial echo including MPI and TDI systolic (S’), early (E’) and late (A’) diastolic velocities of RV and LV during 1st year post HTx. TDI of RV and LV was not available in all donors and was taken from matched controls.

Results:
96 studies (20 donors/controls and 76 recipients) were analyzed (Table

). Increase in LV mass occurred at 7 days, most likely due to post-op tissue edema or ischemic changes with normalization at 3 months. An increase in MPI and a decrease in E’, S’ velocities on TDI occurred at week 1 with gradual improvement within the 1st year (Fig

). Normalization of LV and RV MPI occurred at 6 months and LV TDI velocities at 1 year. TDI velocities of RV at 1 year remained lower than in controls. No patient had > grade IA rejection at follow-up. Myocyte size was measured in H&E-stained on biopsies at 7 days and 1 year after HTx. Although changes in myocyte size varied in individual patients, on average no significant change was found (−3% ± 6%).

Conclusions:
Impairment of bi-ventricular systolic and diastolic function by TDI and MPI occurs early after HTx with gradual improvement during the 1st year. This study provides for the first time the expected values of TDI velocities and MPI of both LV and RV for HTx recipients without significant rejection during the 1st year after HTx.
Abstract 3265: A Comparison of Echocardiographic and Electrocardiographic Characteristics of Patients with Apical Hypertrophic Cardiomyopathy
Authors: Binder Josepha , Grossardt Brandon R , Jost Christine Attenhofer , Klarich Kyle W , Ackerman Michael J , Tajik A. J , Ommen Steve R
Published: July 2021

Background: Apical hypertrophic cardiomyopathy (apical HCM) is a less common subtype of HCM characterized by a focal thickening in the left ventricular apex. “Classic” ECG features have been described, however, apical HCM can persist for many years without detection. We investigated the relationship between ECG findings and echocardiographic morphometry in a large referral series of patients with apical HCM.

Methods: We enumerated all patients diagnosed with apical HCM prior to Sept. 30, 2006 using the Mayo Clinic HCM database. We compared echocardiographic measures separately for patients with positive status for two ECG indices of left ventricular hypertrophy (LVH); the Sokolow-Lyon index and the Romhilt-Estes (RE) point-score. We also compared echocardiographic measurements in patients with and without negative T-waves in the precordial leads.

Results: Apical HCM was detected in 177 patients (111 men and 68 women). Only 51% had positive Sokolow criteria and 51% had positive RE criteria. The agreement between Sokolow and RE status was high (agreement = 75.0%; kappa = 0.50; 95% CI = 0.38 – 0.62). In particular, Sokolow positive patients had increased LV ejection fraction (P = 0.02), and decreased LV end-systolic diameter (P = 0.03) compared with Sokolow negative patients. The prevalence of right atrial enlargement (47 vs. 28%; P = 0.02) and intracavity obstruction (22 vs. 8%; P = 0.01) were more common in Sokolow positive patients. Positive RE criteria was associated with a greater thickness of the basal septal and basal posterior walls (P = 0.001 and 0.02, respectively), and with a higher frequency of intracavity obstruction (21 vs. 9%; P = 0.04). Most patients (89%) exhibited at least one negative T-wave in the precordial leads; however, only 10% of patients had a negative T-wave of greater than 1.0 mV. We found that patients with an inverted T-wave larger than 0.4 mV (median) had a significantly increased LV ejection fraction (P = 0.03) compared with patients who had smaller or no negative T-waves.

Conclusions: Among patients with apical HCM, nearly half do not have ECG evidence of LVH based on classic criteria and most do not have marked T-wave inversions. However, the majority did have at least a mild expression of negative T-waves.
Abstract 3278: Noninvasive Home Monitoring of Pulmonary Artery Pressure by the RemonCHF Device: First Multicenter Experience
Authors: Rozenman Yoseph , Brandt Mathias C , Vanderheyden Marc , Wijns William , Sievert Horst , Tobar Ricardo , Hoppe Uta C
Published: July 2021

Objectives:

A reliable method for home monitoring of the pulmonary artery (PA) pressure might be useful to improve the management of patients with CHF. We describe the feasibility, safety and clinical utility of CHF monitoring using acoustic wireless communication with a miniature implant in the PA.

Methods

: Thirty-eight patients with NYHA class III-IV CHF (age 62.2±2.5 years) were included in a multicenter study. The device was implanted in the right PA using right heart catheterization in 33 suitable patients (due to instability of the implant it was retrieved after implantation in 2 patients). Ultrasonic energy was used for wireless communication and a complete PA pressure curve was recorded daily by patients using a simple, hand-held, home-unit. Home-unit for self monitoring was supplied to 25 patients. Seven patients underwent right heart catheterization at 6 months to assess long term accuracy of pressure measurement.

Results

: There were no major adverse events related to the implant / implantation procedure (follow-up duration 173±54 days). A total of 3094 home measurement were successfully performed by patients (mean±SD, 124±98). Compliance with daily monitoring was 93±16%. Pressure tracings at 6 months were almost identical to those obtained by Millar catheter (mean difference ± SD, 0.4±3.3mmHg). Variations of PA diastolic pressure were observed in relation to posture (sitting 5.5±4.0 mmHg lower than supine, p<0.001), time of the day and medication schedule. Time trends of PA diastolic pressure documented improved hemodynamics following cardiac resynchronization therapy, detected pressure increase earlier than weight gain, and were helpful to adjust medical therapy. Two admissions for CHF decompensation were associated with a transient increase in PA pressure.

Conclusions

: Home monitoring of PA pressure using wireless acoustic communication with a miniature implant in the PA is feasible and safe. Patient’s compliance with self monitoring is very good, and reliable accurate data is easily obtained. Data demonstrated the physiological response to therapeutic interventions (medical and device). Daily monitoring might thus be helpful to optimize therapy of CHF, to improve quality of life and to prevent decompensations.
Abstract 3294: Superoxide-Dependent Cathepsin Activation System is Associated with Hypertensive Myocardial Remodeling and Represents a Target for Angiotesin II Type 1 Receptor Blocker Therapy
Authors: Cheng Xian Wu , Okumura Kenji , Nagata Kohzo , Izawa Hideo , Obata Koji , Sasaki Takeshi , Inoue Aiko , Nishizawa Takao , Yamada Takashi , Kobayashi Masakazu , Inden Yasuya , Murase Yosuke , Kuzuya Mafumi , Shi Guo-Ping , Murohara Toyoaki , Yokota Mitsuhiro
Published: July 2021

Objective:
Cathepsin (Cat) activation contributes to tissue remodeling, and increased Cat activity and superoxide production has been observed in the left ventricle (LV) during heart failure (HF). In the present study we tested the hypothesis that superoxide-dependnet Cat activation inhibition prevents LV remodeling and dysfunction in the development of HF associated with hypertension.

Methods and Results:
We treated 8% salt-loaded Dahl salt-sensitive hypertensive rats (n=10 for each group) with

vehicle

hydralazine (5 mg/kg/d)

E64d (a synthesis Cat inhibitor, 10 mg/kg/d), or

olmesartan (OLM, 5 mg/kg/d) for 8 weeks.

The rats fed 0.3% salt served as age-matched controls. The abundance of Cat mRNAs and proteins localized in cardiac myocytes (CMCs) and Cat-dependent activities were increased in the LV of HF rats and/or humans, and were reduced by OLM treatment. OLM suppressed the elastic lamina degradation by 56% (n=6, p<0.01) concomitant with decreased local Cat S expression in intracoronary smooth muscle cells (SMCs) and restored the balance of elastin to collagen in the LV tissue of HF rats (HF 4.6 ± 0.9% vs. OLM 15.5 ± 2.1% elastin content/collagen content (%), n=6, P=0.031; control 22 ± 2.1%). Furthermore, OLM suppressed not only angiotensin converting enzyme and angiotensin II type 1 receptor (AT
1
R) and macrophage infiltration but also levels of NADPH oxidase components (p22
phox
, gp91
phox
, and p47 phox) concomitant with decreased NADPH activity and O
2
−
production in LV tissues of HF rats and humans. These changes were accompanied by improved cardiac fibrosis, stiffness, and dysfunction. Interestingly, LV remodeling and dysfunction were partially improved by treatment with E64d. In vitro, H
2
O
2
stimulated Cat S mRNA and protein expression and activity, and these increases were abolished by pretreatment with MnTmPyp (50 μ mol/L) and N-acetylcysteine (5 mmol/L) as well as apocynin (100 μ mol/L) in culture CMCs (n=6, p<0.01).

Conclusions:
This is the first report showing that Cats are likely to trigger and promote LV remodeling, and that AT
1
R inhibition exerts inhibitory effect on Cat activation system by the inhibition of NADPH oxidase-dependent superoxide anion production, leading to the prevention of cardiac remodeling and dysfunction.
Abstract 3300: The Impacts of Coronary Artery Calcium on the Diagnostic Accuracy in Detecting Stenoses Using 64-slice Spiral Computed Tomography
Authors: Gao Mingming , Sun Hao , Ma Zhan-Hong , Zhang Lei , Yang Xin-Chun , Xue Yong-Li
Published: July 2021

Objective:
To investigate the diagnostic accuracy of 64-slice spiral computed tomography (MSCT) to coronary artery lesions, and to analyze the impacts of coronary artery calcium to diagnostic accuracy in detecting coronary artery lesions.

Methods:
Sixty patients underwent 64-slice spiral CT and conventional coronary angiography(CCA). Calciumscoring was estimated with plain scans, while 2D and 3D reconstruction were done with enhanced scans. The diagnostic accuracy of MSCT to detect significant lesions was evaluated regarding quantitative coronary angiography (QCA) as the standard of reference, and to analyze the impacts of coronary artery calcium on diagnostic accuracy.

Results:
A total of 797 segments can be diagnosed. The overall sensitivity, specificity, positive predictive value and negative predictive value of 64-slice spiral CT were 96%(174 of 182), 98%(601 of 615), 93%(174 of 188), and 99%(601 of 609) respectively. Within a total of 591 segments with calcium score =0 (Agatston score), the specificity was 100%(498 of 499)and the positive predictive value was 99%(86 of 87). However, 49 segments had a calcium score ≥100, with specificity at 63%(12 of 19)and positive predictive value at 81%(30 of 37).

Conclusions:
In patients with none or moderate coronary calcification, the 64-slice spiral CT coronary angiography allows for the reliable detection of coronary artery stenoses. Severe coronary artery calcification may still degrade the diagnostic specificity and positive predictive value of 64-slice spiral CT.