bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 2616: Role of the Soluble Epoxide Hydrolase in Hypoxic Pulmonary Vasoconstriction and Pulmonary Vascular Remodeling
Authors: Keserü Benjamin , Fisslthaler Beate , Fleming Ingrid
Published: July 2021

The soluble epoxide hydrolase (sEH), which is expressed in pulmonary artery smooth muscle cells, metabolizes cytochrome P450 (CYP) epoxygenase-derived epoxyeicosatrienoic acids (EETs) to their less active diols. Preliminary findings indicate a role of the sEH on hypoxic pulmonary vasoconstriction (HPV) and a vasoconstrictor role of EETs in the pulmonary vasculature. Here we assessed the influence of hypoxia on the expression of the sEH, acute HPV and pulmonary vascular remodeling. In lungs from wild-type mice (WT), exposure to hypoxia (FiO
2
= 0.1) for 21 days decreased the expression of the sEH by 70% (RT-PCR), and increased the number of partially and fully muscularised resistance arteries (by 3-fold). In isolated lungs, pre-exposure to chronic hypoxia significantly increased baseline perfusion pressures (1.3-fold) and potentiated the acute HPV (1.5-fold). While an sEH inhibitor (1-adamantyl-3-cyclohexylurea; ACU) potentiated acute HPV in lungs from mice maintained in normoxic conditions, it had no effect on HPV in lungs from mice exposed to hypoxia. The EET antagonist, 14,15-EEZE, abolished the sEH inhibitor-dependent increase in acute HPV in normoxic lungs. Under normoxic conditions the muscularization of small pulmonary arteries was greater in lungs from sEH
−/−
mice than in lungs from WT mice and chronic hypoxia further increased the number of fully and partially muscularized arteries in these animals. sEH
−/−
mice also displayed an enhanced acute HPV (1.5-fold), compared to that observed in WT mice and chronic exposure to hypoxia did not further potentiate acute HPV. Taken together, these data indicate that the sEH is involved in hypoxia-induced pulmonary vascular remodeling and hypoxic pulmonary vasoconstriction.
Abstract 2618: Bone Morphogenic Protein-9 Stimulates Endothelin-1 Synthesis by Human Pulmonary Microvascular Endothelial Cells: A Possible Contributor to the Pathogenesis of Pulmonary Arterial Hypertension
Authors: Star Greg P , Giovinazzo Michele , Langleben David
Published: July 2021

Pulmonary arterial hypertension (PAH) is thought to be related to progressive obliteration of the pulmonary microvasculature. Endothelial proliferation and dysfunction is a central process, and increased levels of the potent endothelial-derived vasoconstrictor and mitogen, endothelin-1 (ET-1) have been described. It is not known what triggers these increased ET-1 levels. With the description of mutations in receptors for bone morphogenic proteins (BMP) and other members of the TGF-beta family of proteins as causative events in hereditary forms of PAH, we hypothesized that BMPs might modulate ET-1 synthesis. Recently, BMP-9, which acts via the type-1 TGF-beta receptor activin-like kinase 1 (ALK-1), has been identified as a potent regulator of endothelial proliferation and migration. We therefore studied the effects of BMP-9 on ET-1 in-vitro production by human lung microvascular endothelial cells (HLMVEC), the cell implicated in the pathogenesis of PAH. HLMVEC were cultured to confluence in EGM-2MV medium and then BMP-9 (0 –100 ng/ml) was added to the medium for 24 and 48 hours. All concentrations increased ET-1 production at both time points, with 10 ng/ml resulting in a 99% increase versus controls at 24 hours and 104% at 48 hours (all p<0.001). Addition of SB-431542 (10 uM) a specific inhibitor of the kinase activity of ALK-5 significantly reduced the 48 hour ET-1 synthesis provoked by BMP-9, with a 41% decrease for 1 ng/ml BMP-9 but only a 9% reduction for 10 and 100ng/ml BMP-9. In conclusion, this is the first identification of BMP-9 as a potent stimulator of ET-1 production by HLMVEC. Although the actions of BMP-9 are thought to be through ALK-1, there may be a component of interaction with ALK-5, or ALK-5 may have cross-talk with ALK-1. ALK-5 inhibitors such as SB-431542 can reduce BMP-9 mediated ET-1 production and might ultimately have therapeutic benefit for PAH.
Abstract 2655: Polymorphisms in the Gene Encoding for Cyclooxygenase-2 and the Risk of Recurrent Atherothrombotic Events
Authors: Focks Jeroen Jaspers , Clappers Nick , van Oijen Martijn G , Peters Wilbert H , Morsche Rene H te , Roelofs Hennie M , Drenth Joost P , Verheugt Freek W
Published: July 2021

Multiple single nucleotide polymorphisms (SNP’s) in the gene encoding for cyclooxygenase-2 (COX-2) have been identified. These SNP’s may modify risk of atherothrombotic events. The COX-2
-765G->C
SNP has been associated with decreased COX-2 activity and with significantly lower odds of a first atherothrombotic event. The −
1195G->A
SNP on the other hand seems to be correlated with increased COX-2 activity, but has not been investigated in relation to atherothrombotic events. Our aim is to investigate whether these two functional COX-2 SNP’s are associated with the risk of recurrent atherothrombotic events. Patients hospitalized between Apr 2002 and Jan 2004 with acute coronary syndrome were genotyped for the COX-2 −
765G->C
and −
1195G->A
SNP’s and followed up to July 2008. The primary endpoint was a composite of cardiovascular death, myocardial infarction and/or stroke. Multivariate analysis was performed. We included a cohort of 379 consecutive patients (median age 66 y (IQR 55–73), 66% were males). Genotyping for the −
765G->C
showed frequencies of 72% GG, 27% GC and 1% CC. For the −
1195G->A
frequencies were 5% GG, 35% GA and 60% AA. There was strong linkage disequilibrium (D’=−1.0) between both SNP’s. The primary endpoint occurred in 82 patients (22%). The unadjusted hazard ratio for the −
765GC/CC
genotypes was 1.33 (95% confidence intervals [CI] 0.84 –2.10, p= 0.22) compared with −
765GG
, the adjusted hazard ratio was 1.16 (95% CI 0.72–1.88, p=0.54). Haplotype analysis of the combination of −1195- and −765-genotypes, revealed no genetic subgroup at significantly increased risk either. Previously, the COX-2 −
765G->C
SNP was associated with a reduced risk for first atherothrombotic event. For the risk of recurrent events we found no effect for this SNP. In addition we studied the combination with the functional −
1195G->A
SNP of COX-2, which did not show a significant effect on recurrent events either.
Abstract 2751: Correlation of Left Atrial Voltage Maps with Cardiovascular MR Provides Evidence of Pre-existent Scar in Atrial Fibrillation Patients
Authors: Woo Jeongjoo , Peters Dana C , Wylie John V , Nezafat Reza , Hauser Thomas H , Josephson Mark E , Manning Warren J
Published: July 2021

Introduction: There is increasing evidence for and interest in detecting electrically silent left atrial (LA) myocardium which may be the substrate of atrial fibrillation (AF). Late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) might detect these areas of pre-existent scar as high signal in the LA wall. We sought to correlate the extent low-voltage areas in AF patients with clinical parameters of LA volume and type of AF, and to correlate areas of low voltage with areas of high signal on LGE CMR, indicating areas of scarred tissue.

Methods: Twenty-two patients with AF underwent high resolution atrial LGE CMR on a 1.5 T CMR scanner and bipolar voltage electroanatomic mapping (Carto, Biosense Webster). The number of the LA mapping points with low (< 0.1mV) voltage was calculated for each patient. LA systolic volume was measured, indexed to BSA. Using the voltage maps, blood-LA contrast to noise ratio (CNR) was measured on the LGE CMR images in two areas, low and high voltage areas (N=10). Hypothesis testing used t-tests and p<0.05.

Results: The average extent of LA low voltage was 8 % of the LA. Four (18%) patients had no low voltage regions. The extent of low voltage for patients with non-paroxysmal vs. paroxysmal AF was 11 ± 13% vs. 4 % ± 5 % (p=0.08). The extent of low voltage for patients with larger than median LA volumes vs. smaller LA volumes was 12 ± 13% vs. 1 ± 1 % (p=0.027). In 10 patients in which LGE was measured in low and high voltage regions, the CNR was 10 vs. 6 (p=0.016).

Conclusions: Patients with extensive low voltage regions in the LA have larger LA volumes. The CNR is higher in low-voltage regions, suggesting that such regions of possible scar can be identified by LGE CMR.

This research has received full or partial funding support from the American Heart Association, AHA National Center.
Abstract 2797: Progression of Coronary Artery Disease as Assessed by Serial 64-Slice Contrast Enhanced Computed Tomography
Authors: Lehman Sam J , Bamberg Fabian , Schlett Christopher L , Lee Hang , Shturman Leon , Donnelly Patrick M , Rogers Ian S , Brady Thomas J , Hoffmann Udo
Published: July 2021

Volumetric methods to quantify coronary atherosclerotic plaque suffer from high measurement variability, limiting the assessment of plaque progression. We propose a novel semi-quantitative assessment of coronary plaque and determined the rate and predictors of progression in patients with acute chest pain within 2-years. We included 69 patients (mean age 55±12 years, 59% male) from the Rule-Out Myocardial Infarction using Computer Assisted Tomography (ROMICAT) trial who underwent 64-slice coronary CT at baseline and after 2-years (24±3 months). At baseline and follow-up CT, 1-mm cross-sections of the proximal 40 mm of each major coronary artery were reconstructed and assessed for the presence of calcified and non-calcified plaque by two blinded observers. We determined inter- and intra-observer agreement, number of cross-sections with plaque, significance of plaque progression using paired t-test, and predictors of plaque progression over time (adjusted for age and gender) using longitudinal regression analysis. Intra- and inter-observer agreement (k=0.95 and k=0.93) was excellent. At baseline, any plaque, calcified plaque, and non-calcified were detected in 12.5%, 10.1%, and 4.4% of cross-sections per patient. There was significant progression in the mean number of cross section containing any plaque (16.5±25.3 versus 18.6±25.5, p=0.01) and non-calcified plaque (3.1±5.8 versus 4.4_7.0, p=0.04), and no significant increase in calcified plaque (13.3±23.1 versus 14.2±22.0, p=0.2). In unadjusted longitudinal regression models age, male gender, hypertension, hyperlipidemia, smoking, history of CAD, Framingham risk score, and the presence of baseline plaque were significantly associated with plaque progression (P<0.05). After adjustment for age, gender and the follow up time interval, the presence of baseline plaque and smoking were independently associated with increase in plaque progression (P<0.05). We introduce a highly reproducible method to quantify coronary plaque that is able to detect progression over a 2-year follow up period. Increase in plaque was associated with known cardiovascular risk markers.
Abstract 2890: Nesiritide Enhances Myocardial Protection during the Revascularization of Acutely Ischemic Myocardium
Authors: Lazar Harold L , Bao Yusheng , Siwik Deborah , Frame Jeffrey , Mateo Carlos San , Colucci Wilson
Published: July 2021

Nesiritide, a recombinant human B-type natriuretic peptide, has been used in conjunction with inotropic agents in the postoperative management of low cardiac output and pulmonary hypertension. However, its effects on intraoperative myocardial protection are unknown. This study was therefore undertaken to determine whether Nesiritide could enhance myocardial protection when given intraoperatively in a porcine model simulating urgent CABG surgery. Twenty pigs underwent occlusion of the second and third diagonal coronary arteries using snares for 90 minutes followed by 45 minutes of antegrade, cold blood cardioplegic arrest and 180 minutes of reperfusion on cardiopulmonary bypass(CPB) during which time the snares were released. Ten animals received an IV bolus of Nesiritide(2ug/kg) at the initiation of coronary occlusion followed by a 0.01ug/kg/min IV infusion during coronary occlusion, cardioplegic arrest, and reperfusion on CPB. Ten other animals underwent the same protocal without Nesiritide(placebo). Infarct size was assessed by the area of necrosis/area of risk(AN/AR) using histochemical staining, endothelial function by the % change in coronary vasodilation using ring chamber methodology, and lung edema using % change in wet/dry weights. The data is expressed as the mean+/− standard deviation. Nesiritide treated hearts had significantly decreased infarct size, better preservation of endothelial function, and less lung edema. In a porcine model of acute coronary occlusion simulating urgent CABG surgery, the intraoperative infusion of Nesiritide limited myocardial damage. These data suggest that IV Nesiritide infusions may afford increased myocardial protection when administered intraoperatively during the revascularization of acutely ischemic myocardium.

RESULTS
Abstract 3051: Percutaneous Repair of Functional Mitral Regurgitation Using CARILLON
™
Mitral Contour System. Acute Transesophageal Echocardiography Results from AMADEUS
™
Trial
Authors: Siminiak Tomasz , Hoppe Uta C , Schofer Joachim , Haude Michael , Herrman Jean-Paul , Vainer Jindra , Firek Ludwik , Reuter David G , Goldberg Steven L , Van Bibber Richard
Published: July 2021

Left ventricular dilatation with subsequent mitral insufficiency exacerbates heart failure. New techniques for percutaneous repair of Functional Mitral Regurgitation (FMR) are being developed to minimize the high procedural risk of conventional cardiac surgery therapies. To evaluate the feasibility and procedural safety of percutaneous mitral valve repair with CARILLON
™
Mitral Contour System
™
(Cardiac Dimensions® Inc.) in FMR patients AMADEUS
™
trial has been designed. Patients with FMR of both ischemic and non-ischemic origin were enrolled to this multicenter phase I trial. The device is implanted into the coronary venous system and applies tension to the mitral ring in order to improve coaptation of the leaflets. Transesophageal echocardiography (TEE) was used to assess the MR changes. Acute procedural data, obtained in the cath lab immediately before and after the procedure, are reported. Percutaneous mitral annuloplasty in patients with FMR and dilated cardiomyopathy resulted in acute MR reduction (grade 3.0±0.6 to 2.0±0.8, p<0.0001) and permanent device implantation in 30 out of 43 attempts. Additional measurements in final 20 implanted patients showed reductions in vena contracta (0.69±0.29 cm to 0.46±0.26 cm, p<0.0001), effective regurgitant orifice area (0.33±0.17 cm
2
to 0.19±0.08 cm
2
, p<0.0001), regurgitant volume (40±20 ml to 24±11 ml, p= 0.0005), and jet area/left atrial area (45±13% to 32±12%, p<0.0001). Coronary arteries were crossed in 36 patients (84%), but arterial compromise contributed to lack of implantation in 6 patients (14%). All unsuccessful implants were recaptured and removed in these patients without procedural complications. Permanent implantation of the device is safely achievable in the majority of eligible patients resulting in acute MR reduction. Arteries are crossed in most patients and without significant impact. Phase two trials including long term clinical observations on larger number of patients are needed to asses the clinical value of the technique.
Abstract 3083: Implantation of the Medtronic Melody Transcatheter Pulmonary Valve in Patients with Dysfunctional Right Ventricular Outflow Tract (RVOT) Conduits: Procedural and 6-Month Results from the U.S. Feasibility Trial
Authors: McElhinney Doff B , Hellenbrand William E , Lock James E , Jones Thomas K , Cheatham John P , Zahn Evan M
Published: July 2021

RVOT conduit dysfunction can now be treated with transcatheter pulmonary valve placement (TPV). We report procedural and 6-mo outcomes of the prospective multicenter U.S. feasibility trial for TPV using the Melody valved stent. Outcomes included safety, procedural success and short-term effectiveness. Entry criteria included: weight ≥30 kg, RVOT conduit ≥16mm when implanted, and ≥moderate RVOT obstruction (RVOTO; mean gradient ≥40mmHg if NYHA class I, ≥35mmHg if higher) and/or regurgitation (PR; severe if class I, moderate if higher) by echo. Exercise testing, MRI, and chest CT were performed before catheterization (cath). The cath and TPV protocol was standardized, including high pressure balloon angioplasty when needed and balloon sizing of the conduit prior to TPV. In this 5-center study, 58 pts (median age 18 yrs) were enrolled and underwent cath from 1/07–5/08. The mean RVOT gradient on echo was 28±11mmHg and PR was severe or moderate in all but 5 pts. 5 pts were excluded at cath due to risk of coronary compression (2) or other predefined anatomic/hemodynamic factors (3). A Melody was implanted in the RVOT conduit in the other 53 pts. The peak RVOT gradient at cath was reduced from 36±16 to 15±7mmHg (p<0.001) and all pts had no/trivial PR. There were no deaths. In 1 pt, TPV was complicated by conduit rupture, which was managed surgically. Non-surgical complications included atrial tachycardia (1) and PA perforation by a guidewire (1). In 30 pts with 6-mo follow-up data, PR was none (29) or trivial (1) by echo, and mean RVOT gradient was 20±8mmHg, unchanged from discharge (19±8mmHg, p=0.9 by paired analysis). On 6-mo MRI (n=26), median PR fraction was 0%, down from 29% pre-TPV (p<0.001). 1 pt had a second Melody placed 3 mo after TPV for stent fracture and recurrent RVOTO. 8 other pts had stent fractures. There were no other adverse events through 6-mo follow-up, but 2 pts had a second Melody placed for stent fracture with RVOTO ~1 yr post-TPV. In this prospective multicenter study, TPV was safe and technically successful overall, with encouraging acute and 6-mo outcomes. Stent fracture with recurrent RVOTO, observed in ~10% of pts, may be overcome by pre-TPV RVOT angioplasty with or without stent implantation.
Abstract 4089: Unique Epicardial Substrate in Non-Ischemic CM: Echo Signature, Electrogram Correlates and Outcome with Substrate Based Ablation
Authors: Bala Rupa , Cano Oscar , Hutchinson Mathew D , Garcia Fermin C , Riley Michael P , Gerstenfeld Edward P , Cooper Joshua M , Lin David , Dixit Sanjay , Callans David J , Marchlinski Francis E
Published: July 2021

We present a unique series of patients (pts) with non-ischemic cardiomyopathy (NICM) and unmappable ventricular tachycardia (VT) who demonstrated predominantly normal left ventricular (LV) endocardial (ENDO) voltage and abnormal epicardial (EPI) substrate defined by intracardiac echo (ICE) and fractionated electrograms (EGMS). This substrate served as an appropriate ablation target for VT. All patients underwent ICE imaging and detailed ENDO and EPI voltage mapping to further characterize the substrate and define the EGM correlates. 5 pts with NICM had increased echogenicity in the lateral epicardium by ICE imaging. Detailed LV ENDO mapping (199 ± 94.5 points) identified no voltage abnormalities in 4 pts. In one pt, a 16.2cm2 low voltage area in the LV ENDO was present and adjacent to the EPI abnormality. In all pts, detailed EPI mapping (477 ± 158 points) revealed a distinct area (20.6 ± 3.6 cm2) of low voltage (<1.0mV) that correlated with the echogenic area. These areas displayed low amplitude EGMS that were wide (>80msec), split, and late (beyond QRS). (Figure 1

). After excluding coronary branch vessels and the course of the phrenic nerve, all pts underwent substrate based ablation based on pace-mapping and targeting of abnormal EGMS to eliminate the targeted VT. No VT has recurred during mean follow-up of 20mo (range 1–30 mo). Unique EPI substrate in NICM, defined by echo imaging and confirmed by EGM correlates, can be successfully targeted for RF ablation to provide effective VT control.
Abstract 4104: Organization of Atrial Signals is Critical Prior to Cardioversion of Atrial Fibrillation with Intravenous Flecainide: Insight from Spectral Analysis of Intracardiac Electrograms
Authors: Tuan Jiun , Kundu Suman , Jeilan Mohamed , Osman Faizel , Mantravadi Rajkumar , Stafford Peter , Ng G. Andre
Published: July 2021

Introduction & Hypothesis: Studies in catheter ablation of atrial fibrillation (AF) show that an increase in cycle length (CL) and higher organization index (OI) is associated with termination of AF. We hypothesize that similar changes can be seen in chemical cardioversion with Flecainide

Methods: Patients who were still in AF at the end of catheter ablation for AF were given intravenous flecainide. OI and dominant frequency (DF) were obtained by Fast Fourier Transform of coronary sinus electrograms over 10s in AF, before and after flecainide infusion. Mean CL was also calculated.

Results: 28 patients were identified (18 paroxysmal AF and 10 persistent AF). 8 cardioverted to sinus rhythm (SR) with flecainide. In all patients, mean CL increased from 211 ± 44 ms to 321 ± 85 ms (p <0.001). Mean DF decreased from 5.2 ± 1.03 Hz to 3.6 ± 1.04 Hz (p <0.001). Mean OI was 0.33 ± 0.13 before and 0.32 ± 0.11 after flecainide (p = 0.90). Comparing patients who cardioverted to SR with those who did not, OI post-flecainide was 0.41 ± 0.12 vs 0.29 ± 0.10 (p=0.013) and relative change in OI was 29 ± 33% vs −3.9 ± 27% (p=0.016) respectively. No significant difference was noted in the change in CL and DF in the 2 groups. Logistic regression showed that a greater relative increase in OI (p=0.04), a higher OI post-flecainide (p=0.03) and SR at start of procedure (p=0.03) are independently associated with cardioversion to SR with flecainide.

Conclusion: Increase in OI, independent of changes to the CL and DF, appears critical to AF termination with flecainide. The increase in OI may reflect an increase in size and reduction in the number of re-entrant circuits, which together with slowing of atrial activation, result in return to SR.
Abstract 4191: Prognostic Significance of Normal Combined Stress, Delayed Enhancement, and Functional Cardiac Magnetic Resonance Imaging
Authors: Bingham Scott , Hachamovitch Rory
Published: July 2021

Background: Combined adenosine stress perfusion (STRESS), myocardial delayed enhancement (MDE), and ventricular wall motion (WM) by cardiac magnetic resonance (CMR) is a promising approach to further risk stratification in patients with intermediate pre-test clinical cardiovascular risk. The prognosis conferred by normal (NL) STRESS, MDE, and WM CMR is unknown.

Methods: 1,002 consecutive patients underwent combined CMR including STRESS by gadolinium first-pass perfusion, MDE, and cine WM for suspicion of coronary artery disease (CAD) or myocardial ischemia. 577 patients had NL STRESS, 607 had NL MDE, 544 had NL WM, and 448 had NL combined CMR. 70% had no history of CAD. Follow up was performed at a mean 31 (range 12– 62) months after CMR for cardiac death (CD) all-cause death (ACD) and non-fatal myocardial infarction (MI).

Results: NL combined CMR resulted in 0.6% rate of CD per year of follow up (0.3% if no CAD history, and 1.4% with CAD history). Rates for ACD and ACD plus MI were 1.9% and 2.0%. Similar event rates were observed when each component of combined CMR was considered separately.

Conclusion: Normal STRESS, MDE, and WM CMR, both singly or in combination, confer a low risk of subsequent cardiac events.
Event Rate % per Year of Follow Up
Abstract 4491: One-Year Clinical Outcome of a Real World Experience in Patients Treated with a Genous
™
EPC Capturing Stent
Authors: Klomp Margo , Beijk Marcel A , Verouden Niels J , Koch Karel T , Henriques José P , Baan Jan , van der Schaaf René J , Vis Marije M , Tijssen Jan G , Piek Jan J , de Winter Robbert J
Published: July 2021

Background
Clinical trials of drug-eluting stenting (DES) have demonstrated a marked reduction in the incidence of restenosis compared to bare metal stents. However, concerns have risen regarding the long-term safety of DES. The Endothelial Progenitor Cell (EPC)-capturing stent is coated with an antibody (CD34+) that binds circulating EPCs which differentiate into a functional endothelial layer. This accelerated healing may reduce in-stent restenosis by reducing neointimal hyperplasia and smooth muscle cell proliferation and, in addition, may prevent stent thrombosis(ST). In this single center study, we report the 1-year clinical outcome in patients treated with an EPC-capturing stent.

Methods
Between September 2005 and March 2007, 257 patients were treated with an EPC-capturing stent for coronary artery stenosis and 236 patients had completed 1-year follow-up. Dual anti-platelet therapy was prescribed for at least 1 month.

Results
Mean age of the population was 65 years, 72% were male, and 14% were diabetic patients. Three patients had a contra-indication for treatment with a DES, receiving only 2 weeks of clopidogrel post-PCI. A total of 282 lesions were treated of which 252 lesions were treated with an EPC-capturing stent. Of the lesions treated with an EPC-capturing stent, 64% were type B2 or C lesions according to ACC/AHA classification, 16% were CTO and 23% were bifurcated lesions, reflecting daily practice. Mean stent length was 25.13±12.02 mm and mean stent diameter was 3.27±0.36 mm. At 1-year clinical follow-up, 3.0% of the patients died of which 0.8% died from a cardiac cause, and 2.5% of all patients suffered a myocardial infarction. Target vessel revascularization was 9.7% and definite ST was 1.2% (occurring within 24 hours, at 7, and 18 days respectively). At 1-year clinical follow-up the cumulative MACE rate was 11.4%.

Conclusion
In this single center study, PCI of predominantly complex lesions with a Genous
™
EPC-capturing stent shows excellent 1-year clinical outcomes. Furthermore, using this stent avoids the need for long-term dual anti-platelet therapy.
Abstract 4652: Incidence and Mode of AF Termination During Substrate Ablation of AF Guided Solely by Complex Fractionated Atrial Electrograms Mapping
Authors: Oketani Naoya , Lockwood Evan , Nademanee Koonlawee
Published: July 2021

One of the key end points of catheter ablation of atrial fibrillation (AF) substrate guided by complex fractionated atrial electrograms (CFAE) mapping is termination of sustained AF. But controversy exists as to how effective CAFÉ ablation is in AF termination especially in chronic AF. Thus, we carried out the following study to determine incidence and mode of AF termination including electrogram characteristics at the successful site.

Methods: Our study included 616 consecutive patients (pts); 206 (33%) were paroxysmal (PAF) and 410 (67%) chronic (CAF), who underwent CFAE ablation from Jan 2006 to Dec 2007. The recordings of electrograms at baseline, during AF termination and cycle length changes were analyzed blindly off-line; the sites of successful termination were then associated with the detailed grid of 44 regions of both atria and coronary sinus (CS).

Results: Of the 616 Pts, AF could be terminated in 203 (99 %) of PAF (64 pts [31%] with Ibutilide [Ib] ), 80% in CAF (283 pts [69%] with Ib); the remaining 20% of the chronic AF Pts required cardioversion. The termination sites were located 76% in LA, 11% in CS, and 13% in RA. The common areas of the termination are at the upper septum at the anterior aspect of the right pulmonary veins (PVs), proximal CS, posterior aspects of the left PV antrums, the ridge of LA appendage, and postero-septum of RA. AF organized and changed to atrial flutter (Afl) in 121 pts (35%), while 342 pts (65%) of the patients remained in AF with a significant increase (164 to 247 msec) in cycle length before termination. There are 3 distinct electrogram characteristics at the successful sites of tachycardia termination; 1) low voltage CFAE which the shortest cycle length in relation to the rest of the atria (42%); 2) mid-diastolic and fractionated potentials in patients whose AF converted to Afl (45%) and 3) a very low voltage fractionated potentials with the highest amplitude of the potentials was ≤ 0.06 mV (0.044 ± 0.011 mV), commonly found at the previous ablation sites (13%).

Conclusion: Substrate ablation guided by CFAE mapping successfully terminate AF in the majority of Pts. Knowledge of specific areas that have predilection to be sites of termination and electrogram characteristics may be helpful to achieve AF termination.
Abstract 4719: Adenosine Stress Myocardial Perfusion Imaging Using 256-Row Dynamic Volume Computed Tomography
Authors: George Richard , Kitagawa Kakuya , Lautamaki Riikka , Bengel Frank M , Dipaula Tony A , Lima Joao A , Lardo Albert C
Published: July 2021

Dynamic volume computed tomography (DVCT), with full cardiac coverage in one gantry rotation, has the capability of providing simultaneous myocardial perfusion imaging (MPI) of the entire myocardium. The purpose of this study was to assess the accuracy of DVCT-MPI to provide relative measurements of myocardial perfusion. Six canine models of non-occlusive coronary artery stenosis were prepared using an open chest model. Following a 5 minute adenosine infusion, iodinated contrast (24 ml) was infused and DVCT-MPI was performed at peak contrast enhancement using the following protocol: 128 × 1mm collimation, 120 kV, 50 mAs. Radioactive microspheres were injected at the time of DVCT imaging to document myocardial blood flow (MBF). Images were reconstructed in short axis with 3mm slice thickness using segmented reconstruction and enhanced beam hardening correction. DVCT images were analyzed using 8 sectors at the mid-ventricular level and compared with microsphere MBF. Mean MBFs in the ischemic and remote territories were 1.47±0.44 and 2.92±0.54 ml/g/min; respectively p=0.04. Mean change in attenuation densities (from baseline) for the ischemic and remote territories were 42±12 and 65±7 HU; respectively (p=0.01). MBF and attenuation densities in the ischemic territory expressed as a percentage of the remote territory was 60±13% and 52±12%, respectively (mean difference = 8%, p=NS). A representative microsphere MBF map is shown in Panels A and B with corresponding gross pathology and CT-MPI shown in Figures C and D

. MPI using 256-row DVCT is capable of accurately detecting relative differences in myocardial perfusion.
Abstract 4910: Integrated Approach By Using Coronary Flow Velocity Reserve And Coronary Flow Velocity Patterns In Predicting Long-term Adverse Cardiac Events In Acute Myocardial Infarction
Authors: Yoon Myeong Ho , Tahk Seung-Jea , Lim Hong-Seok , Park Jin-Sun , Yang Hyeong-Mo , Choi Un-Jung , Hwang Jung-Won , Hong Hye-Jeon , Kang Soo-Jin , Choi Byoung-Joo , Choi So-Yeon , Hwang Gyo-Seung , Shin Joon-Han
Published: July 2021

Background: The microvascular function was known to be an useful predictor of left ventricular functional changes and clinical outcomes in ST-segment elevation myocardial infarction (STEMI). We evaluated the usefulness of integrated approach by using coronary flow velocity reserve (CFR) and diastolic deceleration time (DDT) in the prediction of long-term major adverse cardiac events in STEMI.

Methods and Results: Using an intracoronary Doppler wire, CFR, DDT and hyperemic microvascular resistance index (MVRI) were evaluated in 202 patients with first STEMI received reperfusion therapy within 24 hours after onset of symptoms. Major adverse cardiac events were the composite of cardiac death, recurrent myocardial infarction, congestive heart failure and stroke during an average follow-up period of 60 ± 39 months. Follow-up echocardiography was performed at 12 ± 9 months. CFR, DDT and MVRI had significant correlations with left ventricular regional wall motion score index at follow-up echocardiography (r =−0.441, p<0.001; r = 0.413, p<0.001; r =−0.485, p<0.001, respectively). Using receiver-operating characteristics analysis, CFR ≤1.3 (sensitivity: 51%, specificity: 78%), DDT ≤577 ms (sensitivity: 72%, specificity: 62%) and MVRI >2.7 (sensitivity: 68%, specificity: 67%) were the best cutoff values in the prediction of occurring the adverse cardiac events. In patients with CFR ≤1.3, DDT ≤577 ms, cardiac events were occurred in 18 patients (40.0 %) of 45 patients, whereas cardiac events were occurred in 12 patients (20.3%) of 59 patients with CFR >1.3 and DDT ≤577 ms or CFR ≤1.3 and DDT >577 ms (p= 0.048), 9 patients (9.1%) of 99 patients with CFR>1.3 and DDT >577 ms (p<0.001). Ejection fraction at admission (p=0.009), MVRI (p =0.002) and DDT (p=0.023) were independent predictors in the prediction of long-term adverse cardiac outcomes during follow-up.

Conclusions: Integrated approach by using CFR and DDT was useful in the prediction of long-term adverse cardiac events. MVRI and DDT were strong independent predictors of long-term adverse cardiac events in STEMI patients.
Abstract 5582: Impact of a Concurrent Chronic Total Occlusion on Long-term Mortality in Hospital Survivors after ST Elevation Myocardial Infarction
Authors: Claessen Bimmer E , van der Schaaf Rene J , Koch Karel T , Baan jan , Tijssen Jan G , de Winter Robbert J , Piek Jan J , Henriques Jose P
Published: July 2021

Background:
Patients with multivessel disease (MVD) constitute a patient group with a high risk of mortality after STEMI. Recently, it was reported that the higher mortality in patients with MVD is determined by the presence of a chronic total occlusion (CTO) in a noninfarct-related artery. Due to the higher risk profile, the in-hospital mortality rate accounted for this unfavorable outcome, moreover, multivariate analysis did not correct for residual left ventricular ejection fraction (LVEF). Therefore, we studied the effect of a concurrent CTO on long-term mortality, excluding deaths in the first 30 days and correcting for LVEF.

Methods:
Between 1997 and 2005, we admitted 3309 patients with STEMI treated with primary PCI. We categorized patients as having single vessel disease (SVD), MVD without CTO and CTO based on the angiogram before PCI. LVEF was assessed with echocardiography by global assessment of ejection fraction within 30 days after primary PCI and classified as ≤40% or >40%. Stepwise Cox regression was used for multivariate analysis.

Results:
LVEF data were available for 1538 patients, of which 1485 (97%) survived the first 30 days after STEMI. SVD was present in 1013 patients (68%), MVD without CTO in 325 patients (22%) and a concurrent CTO in 147 patients (10%). Median duration of follow-up was 3.5 years (IQR 2.1–5.2 years). A total of 104 patients (7.0%) died; 61 (6.0%) in the SVD group, 25 (7.7%) in the MVD group and 18 (12%) in the CTO group (p=0.02). Median time to death was 2.1 years. After correction for the presence of MVD without CTO and differences in baseline variables (age>60 years, residual LVEF ≤40%, diabetes, hypercholesterolemia, smoking, previous MI and shock) the presence of a CTO in a noninfarct-related artery is an independent risk factor for death (Hazard ratio (HR) 1.7, 95% CI 1.0 –2.8, p=0.04). Other independent risk factors are age >60 years (HR 3.0, 95% CI 2.0 – 4.7, p<0.01) and residual LVEF ≤40% (HR 2.3, 95%CI 1.5–3.4, p<0.01)

Conclusion:
After primary PCI, the presence of a CTO in a noninfarct-related vessel, and not the mere presence of MVD, is a strong and independent risk factor for long-term mortality even when adjusted for residual LVEF ≤40% and excluding deaths in the first 30 days.
Abstract 5759: Intramyocardial Application Of Erythropoietin And Expanded Endothelial Progenitor Cells Improve Regional Left Ventricular Function After Induced Myocardial Infarction In Rats
Authors: Stein Andreas , Saraste Antti , Makowski Marcus , Kühnel Sandra , Weidl Elisabeth , Keithahn Alex , Knoedler Martina , Botnar Rene , Schwaiger Markus , Schomig Albert , Ott Ilka
Published: July 2021

Background
: Experimental studies showed that application of expanded endothelial progenitor cells (eEPC) after myocardial infarction improves cardiac function by enhancing vasculogenesis and by paracrine effects. Erythropoietin beta (EPO) could further improve myocardial function through its anti-apoptotic properties.

Methods
: Acute myocardial ischemia was induced by ligation of the left anterior descending coronary artery of 23 male athymic nude rats and reperfusion was initiated after 30 minutes. Either 1×10^6 eEPC alone (n=8), 50 IU erythropoietin beta alone (n=7) or eEPC and EPO (n=8) were injected intramyocardially into the border zone of the ischemic area. eEPC were attained by expanding CD34+ cells isolated from cord blood in endothelial medium for 6 –10 passages. A control group did not receive cells or erythropoietin (n=5). After 4 weeks global and regional left ventricular function was measured by MRI in 2- and 4-chamber long-axis series (Philips Achieva MR Scanner). Immunhistology was used to determine vessel densitiy (SMC actin) and infiltrating monocytes (CD68) after 3 days (n=15) and 4 weeks.

Results
: Global left ventricular function after 4 weeks was higher in rats that received eEPC alone (58±3%, p=.02) or eEPC + EPO (58±6%, p=.01) compared to the control group (54±5%). No changes were found for rats treated with EPO alone (52±4%). Analysis of the regional wall movement showed a further improvement of the movement of the antero-lateral segments only in rats that obtained eEPC + EPO. The number of CD68+ mononuclear cells after 3 days was highest in rats that were treated with eEPC + EPO. This was associated with an increase in vessel density after 4 weeks. In vitro experiments revealed a dose-dependent inhibition of apoptosis by EPO in eEPC.

Conclusion:
Intramyocardial transplantation of eEPCs + EPO further improved anterolateral wall motion as compared to EPC alone. Improved eEPC survival, alterations in local inflammatory responses and neovascularization may contribute to this effect.
Abstract 5765: 3T MRI Molecular Imaging of Benfluorex Treatment of Metabolic Syndrome with α
v
β
3
-Integrin Targeted Nanoparticles
Authors: Cai Kejia , Huang Wenjing , Williams Todd A , Zhang Huiying , Caruthers Shelton D , Lanza Gregory M , Wickline Samuel A , Winter Patrick M
Published: July 2021

1.5T MRI with α
v
β
3
-integrin targeted gadolinium nanoparticle contrast agents (NP) can detect stage I atherosclerosis in experimental animals by localizing specifically to inflammatory plaque components within minutes after injection. We hypothesized that NP could serve as an early surrogate biomarker of therapeutic efficacy for benfluorex treatment of metabolic syndrome in diabetic JCR-LA:cp rats on a 3T clinical scanner. Six week old JCR-LA:cp rats (n=6) received benfluorex in their feed (0.069% wt/wt) for 16 weeks, while control animals (n=5) received regular diet. The abdominal aorta was imaged (T1w spin echo) in 4 cross-sections at baseline and 2-hour post-injection (IV, 1.0 ml/kg NP) every 4 wks with a 3.0 T whole-body clinical MRI scanner, and total aortic wall signal was computed across all sections. Treatment of diabetic JCR-LA:cp rats with benfluorex reduced food consumption and body weight (16.0%; p<0.05); and fasting plasma insulin, leptin and triglyceride were decreased by 52.6%, 18.2% and 36.2% in treated animals. Aortic wall signal for untreated animals rose progressively, whereas signal in treated animals progressively decreased, indicative of attenuation of angiogenesis and vascular inflammation (Figure

, *p<0.05). These observations represent the first report of the use of molecular imaging with an MRI surrogate biomarker at clinical field strength for quantifying therapeutic efficacy in a model of metabolic syndrome.

This research has received full or partial funding support from the American Heart Association, AHA Midwest Affiliate (Illinois, Indiana, Iowa, Kansas, Michigan, Minnesota, Missouri, Nebraska, North Dakota, South Dakota & Wisconsin).
Abstract MP77: Projected Impact of Shifting Population Distributions of Blood Pressure on Rates of Coronary Heart Disease, Heart Failure and Stroke: The Atherosclerosis Risk in Communities Study
Authors: Hardy Shakia T , Loehr Laura R , Butler Kenneth R , Chang Patricia P , Folsom Aaron R , Heiss Gerardo , MacLehose Richard F , Matsushita Kunihiro , Avery Christy L
Published: July 2021

Introduction:
Rates of cerebrovascular disease, heart failure (HF), and coronary heart disease (CHD), increase progressively as blood pressure rises. Several authors have estimated the theoretical effects of shifting the population distribution of blood pressure; however few studies have examined the degree to which modest decrements in blood pressure affect HF incidence, or included a racially diverse population.

Methods:
Incident HF was identified by a first hospitalization with discharge diagnosis code of 428.X. Incident hospitalized (definite or probable) CHD and stroke were classified according to protocol. We used multivariable regression to estimate incidence rate differences (IRD) for HF, CHD, and stroke that could be associated with a two mm Hg reduction in systolic blood pressure (SBP) in 15,744 participants from the Atherosclerosis Risk in Communities Study.

Results:
Over a mean of 18.3 years of follow up, age-adjusted incidence rates for HF, CHD, and stroke were higher among African American than Caucasians (Table 1). After adjusting for antihypertensive use, gender, and age, a two mm Hg decrement in SBP across the total population was associated with an estimated 24/100,000 person-years (PY) and 39/100,000 PY fewer incident HF events in Caucasians and African Americans, respectively. The projected disease reductions were of smaller absolute magnitude for incident CHD and incident stroke. Extrapolation to the African American and Caucasian U.S. populations age greater than 45 years suggests that a two mmHg decrement in SBP could result in approximately 22,000 fewer incident HF events, 15,000 fewer incident CHD events, and 5,000 fewer incident stroke events annually.

Conclusion:
Our results suggest that modest shifts in SBP, consistent with what could theoretically be achieved through population level lifestyle interventions, could substantially decrease the incidence of HF, stroke, and CHD in the United States, especially among African American populations.
Abstract P011: Heart Failure and the Obesity Paradox Among Participants in the in the REasons for Geographic and Racial Differences in Stroke (REGARDS) Study
Authors: Durant Raegan W , Brown Todd M , Levitan Emily B , Richman Joshua S , Redmond Nicole , Glasser Stephen , Safford Monika M
Published: July 2021

Background:
Overweight and obese adults living with heart failure (HF) have lower mortality compared to those of normal weight. However, the specific relationships of overall weight status and central adiposity with mortality among those with HF are less well-defined. We examined the relationships among body mass index (BMI), waist circumference (WC) and mortality among patients hospitalized for HF in the REGARDS Study.

Methods:
REGARDS is a national cohort of US community-dwelling adults aged >45 recruited from 2003 to 2007. We measured all-cause mortality rates among 565 participants hospitalized with HF who were normal weight (BMI 18.5-24.9 kg/m
2
), overweight (BMI 25.0-29.9 kg/m
2
), or obese (BMI > 30.0 kg/m
2
) at baseline. Underweight participants (BMI < 18.5 kg/m
2
) were excluded. Baseline WC, weight, and height were measured during an in-home exam. Index HF hospitalizations during follow-up were adjudicated by a panel of experts. Vital status was determined using the Social Security Death Index or the National Death Index. Cox proportional models estimated hazard ratios for all-cause mortality following the index HF hospitalization. Models were sequentially adjusted for WC, sociodemographics, HF severity (EF and BNP during HF hospitalization, prior history of HF, prior history of diastolic dysfunction), comorbidities, and health behaviors.

Results:
Among 565 participants hospitalized for HF, 116 (21%) were normal weight, 209 (37%) overweight, and 240 (42%) obese at baseline. Over a mean follow-up of 2.5 years, 253 deaths occurred. In multivariable analyses, overweight was associated with lower all-cause mortality in all models (Table). Each 1-cm increase in WC was associated with higher risk of all-cause mortality, but the relationship was not statistically significant after health behaviors were added in the final model. .

Conclusions:
Among adults hospitalized for HF, overweight as assessed by BMI may be associated with lower risk for mortality. However, central adiposity may confer higher risk of mortality.
Abstract P022: Determinants of Energy Balance: Differences Related to Body Weight and Body Composition
Authors: Hand Gregory A , Shook Robin P , Jaggers Jason R , Paluch Amanda , Prasad Vivek K , Burgess Stephanie , Hebert James , Blair Steven N
Published: July 2021

Conversion, utilization and storage of energy in the regulation of energy balance is poorly understood. These misconceptions arise from confusion related to energy balance and its impact on body weight and composition, and can bias the interpretation of findings that are important for the development of policies addressing the obesity epidemic.

PURPOSE:
Our purpose was to examine the regulation of interactions between total daily energy intake (TDEI) and energy expenditure (TDEE) in healthy adults.

METHODS:
Adults not limited by gender, race or ethnicity (n=430; aged 21 to 40; BMI of 20 to 35) participated in a battery of physiological, anthropomorphic, behavioral and psychological measurements that are associated with energy balance regulation. The primary components of energy balance regulation (TDEI and TDEE) were measured by 3 random 24-hour dietary recalls and SenseWear accelerometry, respectively. Body composition was determined by dual x-ray absorptiometry (DXA). Absolute and relative resting metabolic rates (aRMR and rRMR) were determined through hooded indirect calorimetry. General linear modeling was used to examine the relationships of weight and body fatness with TDEI and macronutrient composition as well as the largest components of TDEE including aRMR, rRMR and physical activity energy expenditure (PAEE). In addition, data were compared between participants with a healthy body fat % (below 25; n=123) and obese (at or above 30%; n=241).

RESULTS:
All results were adjusted for age, gender and race. TDEE was positively associated (r=.47, p<.001) with TDEI. There was a positive association between aRMR (L/min) and weight (r=.743, p<.001). By contrast, rRMR (ml/kg/min) was inversely correlated with body weight (r= -.38; p<.001). TDEI was significantly higher in the lean group (2465±66 to 1878±42, p<.001) with no measureable differences in macronutrient percentages. The lean group had a higher TDEE and PAEE as compared to the obese group.

CONCLUSIONS:
There was a robust matching of TDEI and TDEE across weight and body composition ranges. Heavy people burned more calories than lighter people although the lighter individuals had a higher rRMR. The leaner group had a higher TDEI, reflecting a potential regulation based on the greater TDEE in this group. Further, the increased TDEE could be explained by the higher PAEE (approximately 500 kcal) in leaner individuals. These findings emphasize that energy expenditure is related to mass rather than body composition. The regulation of energy intake and body composition is multifactorial, with PAEE a significant determinant for energy storage.
This study was funded through an unrestricted grant from The Coca-Cola Company.