bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 3277: Withdrawal of a Technology-Based Daily Weight Monitoring System in Patients with Advanced Heart Failure Eliminates Mortality Benefit
Authors: Jones Niya A , Frankel David S , Piette John D , Goldberg Lee R
Published: July 2021

Background: Heart failure (HF) is a common, costly cause of hospitalization. Few studies have evaluated the long-term impact of electronic disease management (EDM) on HF care. We reported a mortality benefit among HF patients (pts) undergoing electronic daily weight assessment in the Weight Monitoring in Heart Failure (WHARF) trial. Using trial data on transplant-free survival, we evaluated whether the initial mortality benefit persisted after withdrawal of the EDM system.

Methods: 280 pts from 16 HF centers in the US were randomized, during admission for NYHA III/IV HF, to receive usual HF care or HF care and the AlereNet
TM
system (Alere Medical, Reno, NV). Pts were followed for 6 months prior to removal of the system. Transplant-free mortality data were then examined over the next 50 months.

Results: 138 pts received the EDM system and 142 received usual care. Mean age was 59+/−15 years; 68% male; 64% Caucasian; 75% had NYHA III HF. A 56.2% reduction in mortality was demonstrated for pts randomized to the EDM group (p<0.003). Continued Kaplan-Meier analysis, however, ultimately showed a withdrawal effect among those in this group. By approximately 8 months after removal of the EDM system, mortality rates between the groups were identical. In the early withdrawal phase, mortality among those removed from the technology appears higher. (Figure 1

)

Conclusions: The mortality benefit in the intervention arm did not persist on cessation of the EDM system. This withdrawal effect further supports the notion that technology-based weight monitoring offsets mortality among those with advanced HF. Additional research is warranted to determine the optimal duration of such EDM in HF care.
Abstract 3281: The Prognostic Characteristics of Cardiopulmonary Exercise Testing in Caucasian and African-American Patients with Heart Failure
Authors: Arena Ross , Myers Jonathan , Peberdy Mary Ann , Bensimhon Daniel , Chase Paul , Guazzi Marco
Published: July 2021

Introduction:
Peak oxygen consumption (VO
2
) and the minute ventilation (VE)/carbon dioxide production (VCO
2
) slope are prognostically important in the heart failure (HF) population.

Hypothesis:
We assessed the hypothesis that the prognostic characteristics of peak VO
2
and the VE/VCO
2
slope would be comparable between Caucasian and African-American subjects with HF.

Methods:
Four hundred and ninety one HF patients (339 Caucasian/152 African-American) underwent cardiopulmonary exercise testing and were tracked for major cardiac events for three years.

Results:
The following comparisons are reported as Caucasian vs. African-American subgroups, respectively. Age (56.7 ±14.4 vs. 47.1 ±13.4 years, p<0.001) and ejection fraction (30.6 ±12.9 vs. 25.2 ±11.7%, p<0.001) were significantly lower in the African-American subgroup. Peak VO
2
(15.7 ± 5.6 vs. 14.8 ± 5.7 mlO
2
·kg
−1
·min
−1
, p<0.11) and the VE/VCO
2
slope (35.4 ±9.8 vs. 36.8 ±9.7, p=0.15) were not significantly different. There were 44 (annual event rate: 8.3%) major cardiac events (25 deaths/14 heart transplants/5 left ventricular assist device implantations) in the Caucasian subgroup and 25 (annual event rate: 10.1%) major cardiac events (18 deaths/5 heart transplants/2 left ventricular assist device implantations) in the African-American subgroup. Receiver operating characteristic (ROC) curve analysis and hazard ratios for exercise test variables are listed in Table 1

. Peak VO
2
and the VE/VCO
2
slope were prognostically significant in both subgroups.

Conclusions:
Despite differences in baseline characteristics between Caucasian and African-American subjects, the optimal prognostic threshold values of established exercise testing variables were similar. The VE/VCO
2
slope was the superior prognostic marker in both subgroups. While, peak VO
2
was prognostically significant in Caucasian and African-American subjects, its value was diminished in the latter subgroup.
Abstract 3283: Proximity of Lead Position to Site of Latest Mechanical Activation is Associated With Improvements in Ventricular Dyssynchrony and Function Following Resynchronization Therapy
Authors: Miske Glen , Gorcsan John , Tanabe Masaki , Saba Samir
Published: July 2021

Background:
Left ventricular (LV) lead position for resynchronization therapy (CRT) is routinely done empirically by targeting the posterior-lateral region. Our objective was to test the hypothesis that acute improvements in dyssynchrony and LV function are related to LV lead proximity to site of latest radial activation.

Methods:
We studied 42 consecutive heart failure patients referred for CRT with ejection fraction (EF) 19±13%, and QRS 155±26ms (57% Ischemic) before and 24 hours after CRT. Speckle tracking radial strain (GE Corp.) was used to map mechanical activation time from 12 radial sites; 6 at basal and 6 at mid-LV levels. LV lead tip was localized using anatomic landmarks of the coronary sinus from multiple fluoroscopic views during CRT. Concordance was defined as LV lead tip matching the same site as the latest mechanical activation from the 12 radial sites.

Results:
Overall, group mean radial dyssynchrony improved from 253±127ms to 53±127ms (p<0.05) after CRT. Among the 34 patients with significant baseline radial dyssynchrony (defined as septal-posterior wall delay ≤ 130 ms), lead position was concordant in 24 and discordant in 10. Concordant lead position resulted in greater improvements in dyssynchrony than discordant lead position (58±80ms* vs. 211±120ms) and a greater acute increase in EF (Δ 6±7%* vs. Δ 2±3%) *p< 0.05 vs discordant lead.

Conclusions:
Although empiric LV lead placement for CRT results in acute improvement in LV dyssynchrony overall, concordance of lead position with site of latest activation is associated with greater improvements in dyssynchrony and LV function. These observations have potential clinical implications.
Abstract 443: Transcription Factor E2F2 Regulates Vessel Contractile Function and Blood Pressure via Isoform-specific Expressions of Endothelin Converting Enzyme-1
Authors: Qin Gangjian , Zhu Yan , Kishore Raj , Dinesh Deepika , Thorne Tina , Poh Keong Kian , Losordo Douglas W
Published: July 2021

E2F transcription factors play critical roles in cell cycle regulation but their cardiovascular specific functions are not well defined. Recent studies have revealed a polymorphism in Endothelin Converting Enzyme-1b (ECE-1b) promoter (C-338A), located within E2F consensus site, which is strongly associated with blood pressure (BP) values in hypertensive women. ECE-1, with four isoforms ECE-1a/b/c/d expressed by the use of alternative promoters, is the major enzyme that catalyzes the biogenesis of the potent vessel-constricting peptide endothelin-1 (ET-1) from its inactive precursor Big-ET-1. The role of E2Fs in ECE-1 bioactivity and BP regulation, however, is unknown. Here we provide evidence that E2F2- but not E2F1-deficient mice display an elevated arterial BP. Loss of E2F2 leads to an aortic artery hypercontractility in response to Big-ET-1, indicating an increased ECE-1 bioactivity. ECE-1b promoter-reporter assays, combined with either E2F2 overexpression or knockdown, confirm that E2F2 regulates ECE-1b transcription. The incorporation of C-338A polymorphism in the promoter confers a higher basal level of the promoter activity and blunts the induction of ECE-1b by E2F2. Among all four isoforms, ECE-1b has been suggested to localize in the late endosome and heterodimerize with cell surface ECE-1a/c/d isoforms for lysosomal degradation, thereby down-regulating their activities. Indeed, we found that knockdown of E2F2 leads to a reduced cytosolic however an increased plasma membrane ECE-1 immunoactivity, corroborating with the hypercontractility of E2F2-deficient vessels. These data indicate that in the normal “non-proliferating” vessels, E2F2 plays a critical role in the maintenance of vascular tone. Deregulated E2F2 activity may contribute to the pathogenesis of hypertension.
Abstract 3290: G674A Polymorphism of the Connexin 40.1 Gene and Atrial Fibrillation in Patients With Dilated Cardiomyopahty
Authors: Ogimoto Akiyoshi , Okayama Hideki , Ohtsuka Tomoaki , Suzuki Jun , Kurata Akira , Nishimura Kazuhisa , Nagai Takayuki , Saito Makoto , Miki Tetsuro , Higaki Jitsuo
Published: July 2021

Background:
Atrial fibrillation (AF) is the most common type of cardiac arrhythmia and a leading cause of cardiovascular morbidity. The cardiac gap-junction protein connexin is expressed in atrial myocytes and mediates the coordinated electrical activation of the atria. Some polymorphisms in connexin genes were reported to be significantly associated with AF. We hypothesized that polymorphism (G674A) in the connexin 40.1 gene may be associated with AF in patients with dilated cardiomyopathy (DCM).

Methods and Results:
We genotyped this polymorphism (G674A,
rs595652
) in 83 patients with DCM by using the TaqMan chemical method. Patients were classified into AF group (n=21) if they had AF, and sinus rhythm (SR) group (n=62) if they had SR. Distribution of the connexin 40.1 genotypes (G/G, G/A, and A/A) among the total patients with DCM was 27.7%, 54.2%, and 18.1%, respectively. Allele frequency for the A allele was 0.52 in the AF group and 0.43 in the SR group. In a dominant G allele model (G/G and G/A genotypes vs A/A genotype), there was a significant difference in genotypes between the AF group and the SR group (p=0.035). This table

shows odds ratios for atrial fibrillation in patients with DCM determined by logistic regression analysis. The odds of AF in DCM patients with the A/A genotype was 3.38-fold. In addition, age and left atrial dimension were also risk factors.

Conclusion:
The A/A genotype in the connexin 40.1 gene is a significant risk factor for AF in patients with DCM.

Odds Ratios* for Atrial Fibrillation
Abstract 3299: Association Of The Metabolic Syndrome, Diabetes And Framingham Risk Score With Coronary Artery Calcium
Authors: Ibebuogu Uzoma N , Wong nathan D , Ramirez Jessica , Mao SongShou , Hajsadeghi Fereshteh , gopal Ambarish , flores Ferdinand R , Budoff Matthew J
Published: July 2021

INTRODUCTION:
Coronary artery calcium (CAC) is a sensitive marker for the detection of subclinical coronary heart disease (CHD), and can be accurately quantified using cardiac computed tomography. Few studies have examined the relation between the metabolic syndrome (MetS), MetS risk factor burden, diabetes, and CAC.

HYPOTHESIS:
To examine the relation between MetS, as defined by the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III), MetS risk factor burden, diabetes and CAC.

METHODS:
We studied 356 consecutive, asymptomatic men and women aged 58 ± 11 years who underwent CAC testing, 116 had MetS, 61 had diabetes, and the remainder had neither. MetS was defined according to the NCEP ATP III guidelines with ≥ 3 risk factors. The prevalence and odds of CAC among these groups were determined by multivariable logistic regression analysis. Receiver operating characteristic curves were used to determine if MetS or diabetes added to 10-year CHD estimated by the Framingham risk score (FRS) in predicting CAC.

RESULTS:
The prevalence of CAC >0 for those with diabetes, MetS and neither condition was 73%, 69% and 60% respectively, while the prevalence of CAC ≥ 100 for the 3 groups was 64%, 43% and 24% respectively. Risk factor-adjusted odds for the presence of CAC ≥ 100 were 2.26 (95% CI 1 to 4.4, p=0.0001) among those with MetS and 3.46 (95% CI 1.6 to 7.4, p=0.0001) among those with diabetes, versus neither condition. ROC analysis for CAC ≥ 100 showed an area under the curve of 0.61 (95% CI 0.54 – 0.68) for FRS, 0.72 (95% CI 0.61– 0.83) for diabetes, 0.67 (95% CI 0.56 – 0.77) for the metabolic syndrome, 0.78 (95% CI 0.7– 0.85) when the MetS is added to the FRS (p<0.0001 compared to FRS alone), and 0.90 (95% CI 0.85– 0.95) when diabetes is added to the FRS (p<0.0001 compared to FRS alone). The CAC score showed a trend towards a progressive increase across the metabolic score ranging from 0 to 5 (p=0.0001).

CONCLUSIONS:
Those with MetS or diabetes have an increased likelihood of subclinical atherosclerosis (measured by CAC) compared to those with neither condition, and they also add to prediction of CAC over FRS, suggesting the importance of these factors in clinical assessment of CHD risk.
Abstract 3310: Human Peripheral Blood-derived CD31
+
Cells Have Robust Angio-vasculogenic Properties And Enhance Recovery Following Hindlimb Ischemia
Authors: Kim Sung-Whan , Cho Hyun-Jai , Lee Ji Yoon , Choi Yong Jin , Yoon Young-sup
Published: July 2021

Background: Recently, we reported that murine bone marrow derived CD31
+
cells have hemangioblastic activities. In this study, we hypothesized that human peripheral blood derived CD31
+
cells (hCD31
+
) have robust angio-vasculogenic potential and can induce therapeutic neovascularization in hindlimb ischemia.

Methods and Results: hCD31
+
cells were isolated using a magnetic bead separation technique. By FACS analysis, we confirmed that more than 98% of hCD31
+
cells are positive for CD45, suggesting that hCD31
+
cells are not circulating endothelial cells. In endothelial progenitor cell (EPC) culture assay, hCD31
+
cells almost exclusively gave rise to EPCs and produced significantly higher colony forming activity than hCD31
-
cells (n=5, each) (25.2 ± 2.2 vs. 3.6 ± 0.5/mm
2
, P<0.01). In the matrigel tube formation assay, coculturing HUVEC with hCD31
+
cells revealed that hCD31
+
cells robustly contributed to network formation with HUVECs suggestive of angio-vasculogenic activity. Real-time PCR showed that hCD31
+
cells express higher levels of angiogenic genes (fold increase: angiopoietin-1, 5.6 ± 0.8; HGF, 2.7 ± 0.6; VEGF-A, 3.8 ± 0.5; FGF-2, 2.0 ± 0.5) and lower levels of inflammatory genes (fold decrease: Interferonγ, 13.2 ± 2.5; TNFα, 2.3 ± 0.9) than hCD31
−
cells. To investigate therapeutic potential, we surgically induced hindlimb ischemia in athymic nude mice, and injected hCD31
+
cells, hCD31
−
cells and PBS into the ischemic limbs (n=9, each). The hCD31
+
treated group showed a higher limb salvage rate than other groups [total salvage/tip necrosis/amputation; hCD31
+
cells 5/4/0, hCD31
−
cells 2/5/2, PBS control 0/5/4] (P<0.01). At 14 days, perfusion ratio and capillary density were significantly higher in the hCD31
+
treated group compared to the hCD31
−
and PBS treated groups. Histologic analysis demonstrated that a fraction of injected DiI-labeled hCD31
+
cells exhibit endothelial phenotypes during the follow-up period of 8 weeks.

Conclusion: The present study demonstrated that hCD31
+
cells have robust angio-vasculogenic potential with low inflammatory activity, and enhanced post-ischemia recovery. These data suggested that hCD31
+
cell transplantation may represent a novel therapeutic option for treating ischemic cardiovascular diseases.
Abstract 3313: Smoking Abolishes Ischemic Preconditioning-Induced Augmentation of Endothelium-Dependent Vasodilation: Role of Endothelium-Derived Nitric Oxide and Circulating Endothelial Progenitor Cells
Authors: Higashi Yukihito , Kimura Masashi , Goto Chikara , Jitsuiki Daisuke , Nishioka Kenji , Umemura Takashi , Noma Kensuke , Chayama Kazuaki , Yoshizumi Masao
Published: July 2021

Background: Several studies have shown that both early and late effects of ischemic preconditioning (IPC) protect against myocardial injury following ischemic reperfusion. Recently, we have shown that repetition of IPC stimulus augments endothelium-dependent vasodilation in forearm circulation of healthy subjects through increases in nitric oxide (NO) production and number of endothelial progenitor cells (EPCs) under a local condition. The purpose of this study was to evaluate the late effects of IPC on endothelial function in smokers.

Methods and Results: Late phase of IPC was induced by upper limb ischemia (cuff inflation of over 200 mmHg for 5 minutes) six times a day for one month. We evaluated forearm blood flow (FBF) responses to acetylcholine (ACh) and to sodium nitroprusside (SNP) before and after IPC stimulus in 15 male smokers (27±7 yr) and 15 male non-smokers (26±5 yr). FBF was measured using a strain-gauge plethysmography. The IPC stimulus significantly increased plasma concentration of vascular endothelial growth factor (VEGF) from 84.7±10.6 to 120.3±13.5 pg/mL (P<0.05), circulating level of EPCs from 1258±198 to 1608±183 cells/mL (P<0.05) and FBF responses to ACh from 17.3±4.9 to 24.8±6.9 mL/min/100 mL tissue (P<0.05) in non-smokers, but these did not change in the smoker group. The FBF responses to SNP were similar before and after the IPC stimulus. Infusion of N
G
-monomethyl-L-arginine, a NO synthase inhibitor, completely eliminated the IPC stimulus-induced augmentation of FBF responses to ACh in non-smokers.

Conclusions: These findings suggest that repetition of IPC stimulus may be a simple, safe, and feasible therapeutic technique for endothelial protection of peripheral vessels. However, smoking abolishes repetition of IPC stimulus-induced augmentation of endothelium-dependent vasodilation.
Abstract 3322: Chronic Vascular Responses To Sirolimus-eluting Stent Compared With Bare-metal Stent In Diabetic Patients: Evaluated By Optical Coherence Tomography.
Authors: Kubo Takashi , Imanishi Toshio , Matsumoto Hiroki , Kashiwagi Manabu , Tsujioka Hiroto , Okochi Keishi , Ikejima Hideyuki , Arita Yu , Kuroi Akio , Ueno Satoshi , Kataiwa Hideaki , Tanimoto Takashi , Yamano Takashi , Kitabata Hironori , Takarada Shigeho , Tanaka Atsushi , Nakamura Nobuo , Mizukoshi Masato , Akasaka Takashi
Published: July 2021

OBJECTIVE: An optical coherence tomography (OCT) study was performed to compre the vascular response to sirolimus-eluting stent (SES) with bare-metal stent (BMS) in patients with diabetic mellitus (DM).

BACKGROUND: Despite advances in the medical treatment and revascularization procedures, coronary artery disease remains a leading cause of morbidity and mortality in patients with DM. Few retrospective subgroup analyses of pivotal clinical trials have suggested that SES may be effective for reduction of restenosis in diabetic patients. OCT is a new intravascular imaging method with a high resolution of approximately 10 micrometer and allows us to evaluate instent neointimal hyperplasia (NIH) in vivo.

METHODS and RESULTS: Serial OCT analyses were performed in 60 lesions (SES in DM patients=19; SES in non-DM patients=14; BMS in DM patients=10; BMS in non-DM patients=17) at 9-month follow-up. A total of 6920 stent struts were visualized by OCT and NIH thickness inside each strut and incidence of exposed stnet struts were evaluated in cross-sectional image. The NIH thickness was significantly different among 4 groups (97 +/− 100 vs. 43 +/− 61 vs. 425 +/− 206 vs. 209 +/− 138 micrometer, respectively). The NIH thickness of SES in DM was significantly thicker than that of SES in non-DM (p<0.001), although it was significantly thinner than that of BMS in DM (p<0.001) or BMS in non-DM (p<0.001). All struts of BMS were covered by neointima, but 14% of struts of SES were exposed. The incidence of exposed struts and exposed struts with inadequate apposition in DES were significantly lower in DM compared with those in non-DM (5% vs. 34%, p<0.0001; 2% vs. 5%, p <0.001, respectively). Moreover, the frequency of DES with partially exposed strut was significantly lower in DM than non-DM (32% vs. 71%, p<0.027).

CONCLUSION: The present OCT study revealed that DES inhibited the NIH effectively with low incidence of exposed stent strut in DM patients at 9-month after implantation.
Abstract 448: Platelets Contribute to Arterial and Venous Thrombosis in vivo
Authors: Koellnberger Maria , von Bruehl Marie-Luise , Bergmeier Wolfgang , Wagner Denisa , Mackman Nigel , Massberg Steffen
Published: July 2021

Background: Arterial (AT) and venous thromboses (VT) are the major causes of morbidity in industrialized countries. While the critical contribution of platelets to AT has been recognized, the molecular and cellular mechanisms that trigger the development of VT are not yet fully understood.

Methods: We established a novel model of VT, where thrombus formation occurs after venous stasis in the absence of mechanical endothelial injury. In contrast to published models, our approach closely resembles the triggers that lead to VT in humans. The molecular and cellular events in VT were assessed using intravital and electron microscopy. In particular, we evaluated the differential contribution of platelets (pts) and leukocytes (lcs) to AT and VT.

Results: We found that in AT pts adhere rapidly, whereas only few lcs are recruited. The loss of platelet P-Selectin reduced lc accumulation during AT, was associated with thrombus destabilization, but had no effect on pt adhesion/aggregation. The loss of GPIIb led to a complete lack of pt adhesion/aggregation in AT. While AT largely depends on pts, lc adhesion was the prominent initial phenomenon during VT and involved both P-selectin and Mac-1. P-Selectin−/− as well as Mac-1−/− mice showed a massive reduction in lc accumulation. The lack of P-Selectin was accompanied by a reduction of the thrombus size 48 hours after stasis and was only marginally reduced in Mac 1−/− mice, indicating that lc rolling is sufficient to promote VT. The expression of tissue factor by lcs played a pivotal role for VT. Accordingly, mice with reduced TF expression showed a dramatic reduction in venous thrombus size. In addition to TF-bearing lcs, pts were recruited to the vessel wall early in VT. Pt accumulation involved both the fibrinogen and the vWF receptor and was virtually abolished in mice lacking GPIIb or GPIbα. To our surprise, we observed that pts do not accumulate during VT but play a functional role. Reduced pt adhesion in mice lacking either GPIIb, GPIbα, or VWF was associated with a significant reduction in venous thrombus size.

Conclusion: Together, we show that VT, unlike AT depends on the concerted action of both lcs and pts. Hence, targeting pt activation and adhesion might provide a promising strategy in the prophylaxis and treatment of VT.
Abstract 3329: Discontinuation of Antiplatelet Therapy Correlates with Angioscopic Subclinical Thrombus After Sirolimus Eluting Stent Implantation
Authors: Nishino Masami , Nakatani Shinpei , Hara Masahiko , Hashimoto Akihito , Yamagami Kiyoshi , Matsuoka Ken , Kato Hiroyasu , Egami Yasuyuki , Shutta Ryu , Yamaguchi Hitoshi , Tanaka Kenjiro , Tanouchi Jun , Yamada Yoshio
Published: July 2021

Background: Although some stent thorombois seems to be correlated with discontinuation of antiplatelet therapy, the suitable duration of antiplatelet therapy after silorimus eluting stent (SES) implantation is unknown. In this study, we evaluated effects of discontinuation of one of dual antiplatelet therapy on angioscopic subclincal thrombus in the patients who received dual antiplatelet therapy after SES implantation.

Methods: Six-month follow-up angioscope was performed in 110 consecutive patients with SES implantation. We divided our patients into two groups randomly: the patients who received dual antiplatelet theraphy (aspirin (100mg) and ticlopidine (200mg)/day) until 6-month follow-up angioscope (D-group) and the patients who stopped ticlopidine at 3 months after SES implantation (continued to receive only aspirin) (S-group). We compared the following parameters between the two groups: angioscopic parameters including existence of visible thrombus, grades of neointimal coverage (0: no neointimal coverage of stent struts, 1: partial coverage, 2: complete coverage), plaque color around stent (0: white, 1: yellow) and coronary risk factors including hypertension, hypercholesterolemia, smoking, diabetes mellitus and hemodialysis.

Results: Incidence of angioscopic visible thrombus in S-group was significalty higher than that in D group, while there were no significant differences of the other pamameters between the two groups (table

). Two patients among S-group (3%) and one patient among D group (2%) received revascularization therapy at 6 months after SES implanation (n.s.). All the study patients revealed no other major adverse cardiac events (MACE); death, acute myocardial infarction and coronary bypass surgery.

Conclusions: Only three months discontinuation of ticlopidine may affect on product of angioscopic sublicnical thrombus, however it was not correlated with MACE during 6 months follow-up after SES implantation.
Abstract 3338: Value of a Novel Index of Microcirculatory Resistance for Invasively Assessing Myocardial Viability After Primary Angioplasty in Acute Myocardial Infarction: Comparison With FDG-PET
Authors: Lim Hong-Seok , Tahk Seung-Jea , Yoon Myeong-Ho , Woo Seong-Ill , Choi Woon-Jung , Choi Byung-Joo , Choi So-Yeon , Hwang Gyo-Seung , Shin Joon-Han
Published: July 2021

Background:
Despite the prognostic importance of the status of coronary microcirculation, there has been lacking in comparative studies on the most reliable invasive measurement for assessing microvascular integrity and myocardial viability in AMI. We compared a novel Index of Microcirculatory Resistance(IMR) to intracoronary wire-based physiologic parameters for evaluating myocardial viability after primary percutaneous coronary intervention(PCI) in AMI.

Methods:
After successful primary stenting for 28 patients with AMI, Doppler-derived microvascular resistance index (MVRI) and phasic flow velocity patterns were evaluated. Using a pressure-temperature sensor-tipped coronary wire, thermodilution-derived CFR(CFR
thermo
) and coronary wedge pressure(P
cw
) were measured and the ratio of P
cw
and mean aortic pressure(P
cw
/P
a
) was calculated, along with IMR, defined as the distal coronary pressure divided by the inverse of the hyperemic mean transit time.
18
F-fluorodeoxyglucose(FDG) PET was performed after primary PCI to evaluate myocardial viability by regional percentage uptake of FDG in infarct-related segments.

Results:
Among Doppler-derived parameters, regional FDG uptake showed nice correlation with hyperemic averaged peak velocity(r=0.561, p=0.002), hyperemic MVRI (r= −0.452, p=0.016) and baseline deceleration time of diastolic flow velocity (r=0.505, p=0.006). In the group of pressure-derived parameters CFR
thermo
, P
cw
/P
a
and IMR revealed good correlations with regional FDG uptake (r=0.487, p=0.016; r= −0.469, p=0.012; r= −0.656, p<0.001, respectively). By the receiver operating characteristics curve analysis for prediction of myocardial viability, as defined by the 50% FDG-PET threshold value, the largest area under the curve was acquired by IMR and the best cut-off value of IMR for prediction of myocardial viability was 22U (sensitivity of 79%, specificity of 86% and accuracy of 81%).

Conclusions:
Wire-based coronary physiologic assessment is useful for the prediction of myocardial viability immediately after primary PCI. IMR, a novel index representing the microvascular integrity, is a reliable parameter for the invasive, on-site assessment of myocardial viability after primary PCI in AMI.
Abstract 3346: Percutaneous Treatment Of Unprotected Left Main Coronary Stenoses With Paclitaxel-eluting Stents. Mid-term Results Of A French Prospective Multicenter Study (friend Register)
Authors: Carrié Didier , Eltchaninoff Hélène , Lefèvre Thierry , Silvestri Marc , Levy Gérard , Maupas Eric , Brunel P , Glatt B , Blanchard Didier
Published: July 2021

Purpose : We assessed early and mid-term results of patients (pts) treated for ULMCA disease in the FRIEND registry.

Methods: After ethical committee approval and informed consent, all consecutive pts with unprotected left main stenoses treated with Taxus stents were included in a multicenter prospective study from 23 centers. Major adverse cardiacl events (MACCE) : death, myocardial infarction, stroke, target lesion (TLR), target vessel revascularisation (TVR), acute, sub-acute and late thrombosis were adjudicated at 1and 6 months by an independent committee. Immediate and 9-month angiographic results were assessed by a central core lab. For the distal lesion of ULMCA, a strategy of main branch stenting with provisional T-stenting of the side branch followed by kissing balloon inflation was strongly recommanded.

Results : From December 2005 to July 2006, 155 pts were included, mean age 68 ± 11 years, 83 % male, 31 % unstable angina, 25% diabetics, 46 % 3-vessel disease. The mean Euroscore was 4.2 ± 2.8 (estimated in-hospital mortality rate after surgery 4.1%). The LM reference diameter was 3.6 ± 0.5mm. LM lesion was ostial-proximal in 28 %,mid shaft 18 % and distal 66%. In this group, 72 % were located at the bifurcation including LAD, LCX or both ostia affected. All patients were successfully treated on the LM (stent length 15.7 ± 5.2 mm) and a final kissing balloon inflation was performed in 90%. Apart from the LM stenosis, a total of 1.2 ± 0.8 lesions were treated during the hospitalisation (total stent length 47 ± 16mm). In-hospital MACCE rate was 4.5 % : death in 2.6% (3 acute stent thrombosis at day 2, 3, 5 and 1 before PCI) ; 2 Pts had asymptomatic non-Q-wave MI,1 pt Q-wave MI and 1CABG. At 9-month follow-up (122 pts) there was one extra-cardiac death, no cardiac failure and 3 pts (2.5 %) had recurrence of symptoms. The global rate of event-free survival was 93.5 % with a very low angiographic restenosis rate of 3 %.

Conclusion: LM PCI using the TAXUS stent is feasible and safe. Preliminary results showed favourable 9-month follow-up. Stenting deserves to be considered a safe and effective alternative to CABG in institutions performing large numbers of PCIs. Adjudicated clinical and angiographic long-term (9-month) data are warranted and will be available for presentation.
Abstract 3350: Long-Term Outcomes After Drug-Eluting Stenting of Bifurcation Lesions With the Simultaneous Kissing Stents (SKS) Technique
Authors: Sharma Samin K , Prattipati Madhu , Mares Angelica M , Ivan Oana C , Inamdar Vatsal , Kim Michael C , Kini Annapoorna S
Published: July 2021

Percutaneous coronary interventions (PCI) of bifurcation lesions using simultaneous kissing stents (SKS) technique have shown to have good short-term and mid-term results. Limited data are available regarding long-term outcome with this strategy.

Methods:
We analyzed the long-term outcome of 300 consecutive patients treated with drug-eluting stenting using SKS technique for 305 de novo bifurcation lesions. Cypher stents were used in 265 lesions and Taxus stents were used in 40 lesions, from May 2003 to September 2006 at Mount Sinai Hospital. Clinical follow-up was obtained in 98.6%. All pts were given Aspirin and Plavix 75 mg daily for one year and GP IIb/IIIa inhibitors were used in 72% of cases.

Results:
Overall procedural success was 99% for main vessel (MV) and 98% for side-branch (SB), with one case of intra-procedural stent thrombosis of left main bifurcation. 30-day MACE (MI, death, repeat target vascularization or stent thrombosis) occurred in 5% of cases. Long-term follow-up results at a mean of 14 ± 5 months are shown in the Table

. Overall incidence of stent thrombosis was 1.7% (1.5% for Cypher vs. 2.5% for Taxus). Multivariate predictors of TVR were left main (LM) intervention (odds ratio [OR] 4.97; 95% confidence interval [CI] 2.00 to 12.37, p = 0.01) and diabetes mellitus (OR 4.21; 95% CI 1.15 to 18.56, p = 0.04) and of follow-up MACE were LM intervention (OR 3.79; 95% CI 1.76 to 8.14, p = 0.01) and acute MI (OR 3.24; 95% CI 0.95 to 15.32, p = 0.02).

Conclusions:
The SKS technique for bifurcation lesions using Cypher or Taxus DES is associated with long-term favorable outcomes in this complex, high-risk PCI group. Delayed stent thrombosis with dual antiplatelet therapy remains within acceptable limits. Further work is needed to lower the event rates in some specific subgroups such as LM lesions and AMI settings (perhaps by IVUS guidance and Plavix 75 mg twice a day).
Abstract 3352: Intracoronary Administration Of Bone Marrow-derived Progenitor Cells Abrogates Progressive Left Ventricular Enlargement After AMI: Insights from the REPAIR-AMI Trial
Authors: Assmus Birgit , Schächinger Volker , Erbs Sandra , Elsässer Albrecht , Haberbosch Werner , Hambrecht Rainer , Hölschermann Hans , Yu Jiangtao , Corti Roberto , Mathey Detlef G , Hamm Christian W , Klinik Kerckhoff , Süselbeck Tim , Tonn Torsten , Dimmeler Stefanie , Zeiher Andreas M
Published: July 2021

Left ventricular (LV) enlargement is the most important independent determinant of adverse outcome in patients (pts) after AMI. Depressed LV ejection fraction (LVEF) despite successful reperfusion therapy is the single most powerful predictor of progressive LV enlargement after AMI. Therefore, we investigated whether the intracoronary (i.c.) administration of bone marrow-derived progenitor cells (BMC) alters the association between LVEF within 7 days after successful reperfusion therapy for AMI and enddiastolic (EDV) and endsystolic (ESV) volume expansion at 4 months. In the REPAIR-AMI trial paired quantitative LV angiographic data at baseline (4.3 ± 1 days after AMI reperfusion) and at 4 months follow-up were available in 187 pts. 95 pts received i.c. BMC (4.4±1 days post AMI reperfusion therapy), whereas 92 pts received placebo at 4.3 ± 1 days after reperfusion. Baseline LVEF were similar in the BMC (47±10%) and in the placebo group (48±9 %, p = n.s.). At 4 months, ESV increased in the placebo (+6±22ml), but not in the BMC group (−0.6±19ml, p = 0.04 vs. placebo). Baseline LVEF was inversely correlated with ESV expansion at 4 months in the placebo, but not in the BMC group (figure

). Likewise, EDV expansion was closely correlated with baseline LVEF in the placebo (r=−0.36, p<0.001), but not in the BMC group (r=−0.17, p=1.0). Finally, ESV expansion determined changes in NT-proBNP serum levels in the placebo (r=−0.38, p=0.006), but not in the BMC group(r=0.05, p=0.68).

Conclusion: I.c. administration of BMC eliminates the correlation between depressed LVEF after reperfusion therapy and LV expansion during follow-up and thereby abrogates progressive LV enlargement after AMI.

Change in endsystolic volume (baseline to 4 months , ml)
Abstract 3361: Progressive Left Ventricle, Myocyte Dysfunction, and Heart Failure in the Lethality of Anthrax Toxin in Conscious Dogs
Authors: Cheng Che-Ping , Masutani Satoshi , Cheng Heng-Jie , Cross Michael , Zhang Chun-Xian , Zhou Peng , Cann Jennifer , Cline J. Mark , Little William C , Kuo Shu-Ru , Frankel Arthur E
Published: July 2021

Background
.
Bacillus anthracis
(
BA
) infection is a cause of human and animal disease and associated with biowarfare. Although circulatory shock related to anthrax lethal toxin (LeTx) may play a primary role in lethality due to
BA
infection, its mechanisms are unclear.

Methods
. Six chronically-instrumented conscious dogs were assigned to receive a bolus injection of LeTx (10 ml saline with equivalent doses PA/LF, about 0.265 mg/kg, iv, n = 2) or saline (10 ml, iv, n = 4). Hemodynamic, left ventricular (LV) systolic and diastolic responses were determined periodically until 96 hours (h) in both groups. LV biopsies were performed at about 98H (before death). Isolated myocyte contractile function and histopathological alterations were determined.

Results
. Compared with control, in LeTx-treated animals, there were progressive decreases in LV contractility and slowed LV relaxation during the transition from LV dysfunction to heart failure (HF) over 96–98H. The cardiac depression was apparent about 6 – 8H after LeTx, but progressed through the subsequent 72–98H. At 72H after LeTx, heart rate (LeTx:129vsControl:95 bpm), LV end-diastolic pressure (P) (21vs9 mmHg), and the time constant of relaxation (40.9vs29.7 ms) were increased with markedly reduced ejection fraction, stroke volume (SV, 8.4vs15.8 ml), and end-systolic P (92vs118 mmHg). Moreover, LV contractility was decreased 49% (E
ES
, 4.1vs8.2 mmHg/ml and M
SW
, 44.9vs88.9 mmHg) with rightward shifts of LV P-V loops. At 96H, M
SW
, SV, and EF were further decreased accompanied by the development of severe HF. Pathologic finding of LV dilatation was associated with significantly increased length of LV myocytes (201±11vs122±13 μm). In LeTx-treated myocytes, there were about 46% reductions in cell contraction (79.0±9.7vs146.2±11.4 μm/s) and relaxation, respectively. LeTx produced lethality in dogs 4 days after LeTx treatment with similar time courses to those previously reported in man.

Conclusions
. LeTx causes direct and time-dependent progressive decrease in LV contractility, slow relaxation, cardiomyocyte dysfunction, LV, and myocyte remodeling and leads to HF, which suggests that the heart could be the primary target for the action of LeTx and plays an important role in lethality due to
BA
infection.
Abstract 3363: Quantitative In Vivo T2 Measurements Differentiate Both Infarcted and Peri-Infarct from Normal Myocardium
Authors: Aletras Anthony H , Kellman Peter , Mohanty Bibhu D , Hoyt Robert F , Arai Andrew E
Published: July 2021

Introduction:
T2-weighted MRI, which reflects water content and mobility, has been recently shown to delineate the area at risk (AAR). However, in-vivo T2 measurements within the viable and infarcted regions of the AAR have not been presented to date. We hypothesized that state-of-the-art T2 methods could discriminate different T2 relaxation constants not only between the AAR and remote myocardium but also between viable and infarcted tissue within the AAR.

Methods:
Acute myocardial infarction was created by coronary occlusion (90 min N = 9, 180 min N = 5) followed by reperfusion in canines. In-vivo imaging was performed 3 days post-infarction at 1.5T. T2-prepared steady-state free-precession (T2P-SSFP) was used to measure T2 prior to Gd-DTPA infusion. Infarct size was determined by delayed contrast enhancement.

Results:
T2 Bright regions within the left anterior descending coronary artery were detected in all experiments and were larger and generally of greater transmural extent than the regions of delayed enhancement. Using regions of interest determined by the delayed enhancement, T2 showed step-wise abnormalities from normal to peri-infarct and infarcted myocardium (45 +/−4 vs 60 +/−5 vs 67 +/−5 ms; all pairwise comparisons significant). A threshold T2 of 54 ms distinguished normal from abnormal in all but one region.

Conclusions:
The degree of edema or mobility of water varies between infarcted myocardium and the peri-infarct zone and both are significantly different from normal. Due to the subtlety of T2 abnormalities in the heart, parametric maps can display T2 in an objective manner and could improve the diagnostic value of T2 weighted MRI of infarction and myocarditis.
Abstract 3364: Serial MRI Assessment of Macrophage Activity in the Murine Heart after Myocardial Infarction using Gadolinium-labeled Liposomes as a Positive Contrast Agent
Authors: Xu Yaqin , Klibanov Alexander L , Beyers Ronald J , Helm Patrick , Vandsburger Moriel H , Janiczek Robert L , French Brent A , Epstein Frederick H
Published: July 2021

Introduction:
Macrophage activity in the heart after myocardial infarction (MI) has previously been assessed by iron-particle cardiac magnetic resonance (CMR) that produces negative contrast. We hypothesized that a new multimodal, liposomal agent with both Gd-DTPA and fluorescent DiI dye could be used for positive contrast macrophage tracking.

Methods:
Multimodal liposomes (ML) were prepared with Gd-DTPA-bis-stearylamide and DiI then filtered to ∼0.3 μm size. Nine C57Bl/6 mice were subjected to 1h coronary occlusion followed by up to 7d of reperfusion. ML volumes of 50μl were injected IV on Day 2 post-MI for monocyte/macrophage phagocytosis. Mice were studied by CMR 2–4h after Day 2 injection and daily until Day 7 post-MI. CMR included inversion-recovery (IR) to image ML followed by IP infusion of Gd-DTPA and more IR to image the entire infarct (IF). After final imaging, hearts were removed for Mac2 immunostaining & fluorescence microscopy.

Results:
Day 2 IR CMR 2–4h after ML injection revealed strong signal enhancement in the spleen with none in the heart. In all mice from Day 3–7, ML signal enhancement marked the LV anterior wall in IF regions (Fig A

). The ML contrast peaked at Day 5 and decreased by Day 7 post-MI (Fig B

). In mice euthanized at Days 4 & 7, ML-enhanced regions corresponded well with regions containing macrophages as labeled by anti-Mac2 (Fig C

) and DiI (Fig D

)

Conclusions:
ML can assess the accumulation of macrophages in the heart until at least Day 7 post-MI. The Gd tag provides specific positive contrast and the fluorescent tag expedites histological confirmation. This improves over iron-based agents that preclude complementary CMR imaging in regions containing iron.
Abstract 454: Mechanism of Alpha-Synuclein Inhibition of Platelet Granule Exocytosis
Authors: Srivastava Kalyan , Lee Michael , Morrell Craig
Published: July 2021

Alpha-synuclein is only expressed in the brain and platelets. The normal function of alpha-synuclein in the brain is not known, but studies indicate it is an inhibitor of exocytosis in platelets. Platelet granule exocytosis is an important step in stable thrombus formation and its regulatory mechanisms are poorly defined. We therefore sought to determine the mechanism of alpha-synuclein inhibition of exocytosis. Using platelets from alpha-synuclein knockout (syn−/−) mice we first confirmed that syn−/− mice have increased alpha-granule release in response to agonist stimulation as compared to wild-type (WT) control mice. Using a mesenteric intravital microscopy model, we have also found that syn−/− mice have shortened time to thrombus formation as compared to wild-type control mice. The granule exocytosis and thrombosis phenotypic changes are restored to normal in syn null mice made transgenic to express human alpha-synuclein, clearly demonstrating that alpha-synuclein is an inhibitor of exocytosis in platelets. We have also determined the mechanism by which alpha-synuclein inhibits platelet granule exocytosis. Alpha-synuclein interacts with the exocytosis associated molecule Rab3, a modulator of the ATPase molecule N-ethylmaleimide Sensitive Factor (NSF). NSF activity is necessary for exocytosis and is increased by Rab3 interactions. Using platelet lysates, addition of an excess of recombinant alpha-synuclein inhibits NSF and Rab3 co-immunoprecipitation. Furthermore, syn−/− mouse platelets have increased Rab3 immunoprecipitation with NSF as compared to WT controls, that is restored to normal in synuclein Tg mice. Using recombinant tagged alpha-synuclein, NSF, and Rab3 in pull down assays we have confirmed that alpha-synuclein inhibits NSF-Rab3 interactions, and furthermore, decreases NSF ATPase activity. In summary, we now demonstrate using in vitro, ex vivo, and in vivo models that alpha-synuclein is a negative regulator of platelet granule exocytosis by inhibiting NSF-Rab3 association and thus NSF ATPase activity.
Abstract 455: Peri-interventional Antiplatelet Effect of Clopidogrel in Patients Undergoing Percutaneous Coronary Intervention is Attenuated by Cytochrome P450 2C19*2 Polymorphism
Authors: Trenk Dietmar , Hochholzer Willibald , Krozingen Herz-Zentrum Bad , Fromm Martin F , Chialda Ligia , Pahl Andreas , Neumann Franz-Josef
Published: July 2021

The thienopyridine derivative clopidogrel is an inactive pro-drug requiring biotransformation by cytochrome P450 isoenzymes (CYP) in order to generate an active metabolite. This metabolite inhibits irreversibly the platelet P2Y12 receptor, thereby exerting the antiplatelet effect of the drug. The EXCELSIOR study showed a 7-fold 30-day risk of major adverse cardiac events in patients with inadequate peri-interventional platelet response to loading with clopidogrel 600 mg. Studies in healthy volunteers on the impact of the CYP2C19 genotype to the interindividual variability in antiplatelet effect of clopidogrel showed conflicting results. The EXCELSIOR study enrolled 802 patients undergoing elective percutaneous coronary intervention (PCI) with stent implantation. The antiplatelet effect of a loading dose of clopidogrel 600 mg was determined by optical aggregometry (5μM ADP) before administration of clopidogrel, at the time of PCI and pre-discharge at day 1after PCI. CYP2C19 genotype (681G>A) was analyzed in 697 patients by real-time PCR. Antiplatelet efficacy of clopidogrel was determined for the different genotypes. Within the subset of the EXCELSIOR cohort, 485 patients (69.6%) were CYP2C19 wild-type homozygous (*1/*1), 199 (28.6%) were CYP2C19*1/*2 and 13 (1.9%) were CYP2C19*2/*2 carrying two allelic variants encoding a deficient CYP2C19 enzyme. Residual platelet aggregation (median; interquartile ranges) determined 5 minutes after addition of ADP 5μM is summarized in relation to the CYP2C19 genotypes in the Table

below. These results indicate that the antiplatelet response to a loading dose of clopidogrel 600 mg is substantially attenuated in patients carrying at least one CYP2C19*2 allele. It seems that the CYP2C19 genotype is a major factor contributing to the observed variability in the antiplatelet effect of clopidogrel and might therefore affect clinical outcome of patients undergoing PCI.

Relationship Between Genotype and ADP-induced Platelet Aggregation (%)
Abstract 456: Antiphospholipid Antibodies Promote Platelet Activation and Thrombosis by Inhibition of Platelet eNOS
Authors: Morrell Craig , Swaim AnneMarie , Martin Tanika , Girardi Guillermina , Salmon Jane E , Mineo Chieko , Shaul Phillip
Published: July 2021

The antiphospholipid syndrome (APS) is an autoimmune systemic disorder characterized by the persistent presence of antiphospholipid antibodies (aPL Ab) and increased risk of thrombosis, coronary artery disease and myocardial infarction. Although platelets are known direct targets of aPL Ab action, the molecular basis of aPL Ab actions on platelets remains unclear. Platelet endothelial NO synthase (eNOS) is a key regulator of platelet function, with NO causing blunted activation. We therefore determined whether aPL Ab modulate platelet eNOS. Normal human IgG (NH IgG) and human IgG containing polyclonal aPL Ab were obtained from healthy individuals and APS patients, respectively, and purified using protein G-Sepharose chromatography. Using both human and mouse platelets, we found that aPL Ab increased agonist-induced platelet activation whereas NH IgG did not. In contrast to the enhanced activation by aPL Ab in platelets from wild-type mice, aPL Ab had no effect on platelets isolated from eNOS null mice. Pre-treatment of platelets with aPL Ab also inhibited insulin-mediated eNOS stimulation as evidenced by diminished cGMP production and DAF2 fluorescence. Receptor associated protein (RAP), an antagonist of ligand binding to members of the LDL receptor family, blocked aPL Ab-induced increases in platelet activation. RAP also prevented aPL Ab-mediated antagonism of platelet eNOS, indicating that aPL Ab signal through the platelet ApoER2â ϵ™ (LRP8) to attenuate eNOS activity. Furthermore, using intravital microscopy of the mouse mesenteric circulation, we demonstrated that platelets from wild-type mice treated with aPL Ab have increased rolling on a stimulated endothelium and a decreased time to thrombus formation in vivo versus platelets treated with NH IgG. In contrast, aPL Ab did not alter the in vivo function of platelets from eNOS null mice. These cumulative in vitro and in vivo findings demonstrate that aPL Ab antagonism of platelet eNOS through LDL receptor family member binding underlies aPL Ab-mediated thrombosis.