bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 2805: Persistent Gender Bias in the Use of Percutaneous Coronary Intervention at the Acute Stage of MI from 1995 to 2005: Results from the French USIK, USIC 2000 and FAST-MI Registries
Authors: DANCHIN Nicolas , SIMON Tabassome , ELTCHANINOFF Helene , GILARD Martine , OLTEAN Ioana , LECLERCQ Florence , MULAK Geneviè ve , CAMBOU Jean-Pierre
Published: July 2021

Percutaneous coronary intervention (PCI) is an essential step in the management of patients with STEMI or NSTEMI. Previous data have evidenced a gender bias in the use of PCI in people admitted for AMI.

Aim: to assess whether PCI was used differently in men and women with AMI and if there have been changes in this regard over the last 10 years.

Methods: USIK 1995, USIC 2000 and FAST-MI are 3 nationwide French registries conducted 5 years apart, using a similar methodology in patients admitted to CCU over a one-month period. For the present analysis, all 7528 patients admitted for AMI (STEMI and NSTEMI) < 48 hours from symptom onset were included.

Results: 2152 patients were included in 1995, 2317 in 2000 and 3059 in 2005. Women represented 29%, 27% and 32% of the populations, respectively in the 3 periods. Overall, women were 10 years older than men (no difference between the 3 periods); PCI was used in 53% of men and 39% of women (p<0.001). Use of PCI during the initial hospital stay increased from 1995 to 2005, but the difference between men and women persisted (1995: 12% v. 20%; 2000: 45% v. 62%; 2005: 52% v. 69%)(p<0.001 at all time points). In the whole population, female gender was an independent predictor of a lower use of reperfusion therapy (OR: 0.70; 95% CI: 0.62– 0.79, p<0.001), together with older age, history of peripheral arterial disease, history of congestive heart failure, and earlier time period (1995 v 2000 v 2005) (logistic regression analysis). In each of the 3 periods, female gender remained associated with lower use of reperfusion, with odds ratios of similar magnitude (1995: OR: 0.54, 95% CI: 0.41– 0.71; 2000: OR 0.50, 95% CI: 0.41– 0.60; 2005: OR: 0.48, 95% CI: 0.41– 0.56). A striking decrease in 30-day mortality was observed in women (1995: 21%, 2000: 12%, 2005: 8.5%). This decrease, however, was found predominantly in women who underwent PCI (14%, 6% and 4%, respectively), compared with women without PCI (22%, 17%, 14%, respectively).

Conclusion: In spite of a much higher use of PCI over the past 10 years, a definite gender bias persists. This finding is all the more preoccupying as the reduction in early mortality over this period of time has been observed mainly in women with PCI.
Abstract 2835: Waveform Characteristics of Ventricular Fibrillation Are Altered in Post-Myocardial Infarction Swine
Authors: Indik Julia H , Donnerstein Richard L , Feigelman Justin , Hilwig Ronald W , Zuercher Mathias , Kern Karl B , Berg Marc D , Berg Robert A
Published: July 2021

Background: In ventricular fibrillation (VF) of short duration chest compressions do not improve survival prior to defibrillation. We have previously shown that in an acute myocardial infarction (MI), frequency characteristics are markedly depressed and are poor surrogates for VF duration. We hypothesized that the VF waveform further evolves post-MI, after a myocardial scar has formed.

Methods: Acute myocardial infarction was induced in nine swine by occlusion of the mid left anterior descending artery. After a two week recovery period, VF was induced and compared to VF in 16 control swine over the first five minutes. VF waveforms were analyzed for frequency content (mean, median, dominant and bandwidth), slope (the median of the absolute value of the difference in voltage every 5 ms), and AMSA (the summed product of amplitude and frequency).

Results: Myocardial scar was confirmed in all MI swine postmortem. All frequency characteristics were significantly altered in post-MI swine (p<0.01). At 4 minutes, VF mean frequency in controls was 10.3 ± 0.5Hz compared to 9.1± 0.5Hz in post-MI swine (mean ±SEM, p=0.007), with similar differences for median and dominant frequencies. Bandwidth was markedly decreased and at 4 minutes was 3.2 ± 0.2Hz in controls compared to 2.1 ± 0.2Hz in post MI swine (p<0.001). However, slope and AMSA were similar in both groups.

Conclusions: Frequency content of VF remains altered post MI compared to control swine, with reductions in mean, median and dominant frequencies and larger reductions in bandwidth. Amplitude based measures such as AMSA and slope, however, are not significantly altered and may serve as better predictors of time in VF.
Abstract 2860: Efficacy and Safety of Vernakalant Hydrochloride Injection for the Treatment of Atrial Fibrillation After Valvular or Coronary Artery Bypass Surgery
Authors: Kowey Peter R , Roy Denis , Pratt Craig M , Schwartz Peter J , Dorian Paul , Mitchell L B , Toft Egon
Published: July 2021

Introduction:
Postoperative atrial fibrillation (AF) and atrial flutter (AFL) are common after cardiac surgery. This study evaluated the efficacy and safety of vernakalant hydrochloride, a novel atrial selective, frequency- and voltage-dependent Na
+
and early activating K
+
channel blocker, in converting AF or AFL to normal sinus rhythm (SR) after coronary artery bypass surgery (CABG), valvular surgery, or both.

Methods
: This multicenter, double-blind, randomized, placebo-controlled trial included patients aged ≥18 years who had normal SR preceding surgery; had undergone CABG or valvular surgery; and had documented, sustained (3–72 hours) AF or AFL between 24 hours and 7 days after CABG or valvular surgery. Patients were randomly assigned in a 1:2 ratio to receive a 10-min infusion of placebo or vernakalant 3 mg/kg. After 15 min, a second 10-min infusion of placebo or vernakalant 2 mg/kg was given, if AF or AFL persisted. Postdose evaluations included 24-hr Holter monitoring, 12-lead ECG recordings, and assessment of vital signs and AF/AFL symptoms. The primary efficacy measure was conversion to SR for at least 1 minute within 90 min of first exposure.

Results
: Of 190 patients randomized, 161 received treatment (54 placebo and 107 vernakalant). The main reason for not receiving treatment was spontaneous conversion to SR (7 placebo and 17 vernakalant). Among the patients given treatment, 67% had undergone CABG, 24% had valvular surgery, and 9% had both. The mean age was 68 years, and most patients were men (75%) and white (94%). At entry, 93% of patients had AF, 6% had AFL, and 1% had neither. Conversion to SR within 90 minutes was observed in 45% of patients given vernakalant and 15% of those given placebo (
P
= .0002). Of the patients converting to SR with vernakalant, the median time to conversion was 12 minutes and 75% converted on the first dose. In the 24-hr period following study drug administration, adverse events were reported in 32% and 38% of patients given placebo and vernakalant, respectively, of which 2 were serious (complete AV block and hypotension) in the vernakalant group. There were no deaths or cases of torsade de pointes.

Conclusions
: Vernakalant was effective and well tolerated in the conversion of AF and AFL to SR after CABG, valvular surgery, or both.
Abstract 2864: Antiarrhythmic Effect of Statins and Atrial Fibrillation: A Meta-analysis of Randomized Controlled Trials.
Authors: Fauchier Laurent , Pierre Bertrand , Grimard Caroline , de Labriolle Axel , Breard Guillaume , Zannad Noura , Clementy Nicolas , Babuty Dominique
Published: July 2021

The use of statins has been suggested to protect against atrial fibrillation (AF) in some clinical and experimental studies but remained inadequately explored. Specifically, observational studies provided evidence supporting a protective role of statins against atrial fibrillation. However, insufficient data are available at this time to allow recommendations for prevention of AF using statins. In order to improve the evaluation of their possible benefit, we performed a metaanalysis of randomized trials with statins on the endpoint of incidence or recurrence of atrial fibrillation.

Methods.
A systematic review of controlled trials with statins was performed. Data sources included Medline, Embase, Cochrane central register of controlled trials, and hand search. Predefined criteria were used to select controlled clinical trials. Eligible studies had to be randomized, controlled, parallel-design human trials with use of statins that collected data on incidence or recurrence of atrial fibrillation. Data were extracted for patients’ characteristics, interventions, quality of trials, and rates of events.

Results.
Four studies with 430 patients in sinus rhythm were included in the analysis. Three studies investigated the use of statins in patients with a history of paroxysmal AF (n = 1) or persistent AF after electrical cardioversion (n = 2) and one in primary prevention of AF in patients undergoing cardiac surgery. Coronary artery disease was present in 179/430 patients (42 %). Beta blockers were prescribed in 243/430 (57 %) and amiodarone in 7/430 (1.6 %) of the patients. Incidence or recurrence of atrial fibrillation occurred in 190 patients: 70/216 in patients treated with statin vs 120/214 in controls. Thus, the use of statins was significantly associated with a decreased risk of atrial fibrillation compared to control (relative risk 0.37, 95% confidence interval 0.25 to 0.55, p < 0.0001).

Conclusions.
In randomized trials, use of statins in patients in sinus rhythm with a history of previous AF or undergoing cardiac surgery was significantly associated with a decreased risk of incidence or recurrence of atrial fibrillation.
Abstract 2889: Prediction of Cardiac Stability after Weaning from Left Ventricular Assist Devices in Patients with Idiopathic Dilated Cardiomyopathy
Authors: Dandel Michael , Weng Yuguo , Siniawski Henryk , Potapov Evgenij , Drews Thorsten , Lehmkuhl Hans B , Knosalla Christoph , Hetzer Roland
Published: July 2021

Background:
The use of ventricular assist devices (VADs) as bridge to transplantation (Tx) has become a standard therapeutic option in end-stage heart failure (HF). During unloading clinical recovery which allows reliable weaning from VADs is possible. After 12 years of weaning experience, we searched for parameters that are predictive for post-weaning cardiac stability and thus helpful for future weaning decisions.

Methods:
With regard to potential prediction of weaning success we evaluated echocardiographic parameters obtained during final ``off pump” trials before VAD explantation, histological changes and serum anti-ß1-adrenoreceptor autoantibody disappearance during unloading, duration of mechanical support and duration of HF. Among 79 patients weaned since 3/1995, a homogenous group of 35 patients with idiopathic dilated cardiomyopathy (IDCM) weaned from LVADs were selected for evaluation.

Results:
The 8-year post-weaning survival reached 78.1 ±8.2%. Freedom from HF recurrence at 4 years after weaning was 69.3 ±8.1%. Patients with post-weaning cardiac stability were younger, history of HF and recovery time during unloading shorter, LV short/long axis ratio lower (less spherical) and systolic wall motion velocity (measured by tissue Doppler) higher (p< 0.05). For LVEF ≥ 45% at LV enddiastolic diameter (LVEDD) ≤ 55mm the positive predictive value for ≥ 4 years cardiac stability reached 90.5%. There was no HF recurrence during the first 4 years in patients with LVEF ≥ 45%, LVEDD ≤ 55% and history of HF < 5 years. The time course of LVEF during the first 6 months also appeared predictive for long-term stability after weaning. History of HF > 5 years showed a predictive value of 90% for HF recurrence during the first 3 years. Neither reduction in myocardial hypertrophy and fibrosis nor serum anti-ß1-adrenoreceptor autoantibody disappearance during unloading appeared predictive for post-weaning stability.

Conclusions:
Off-pump LVEF and LVEDD, time course of LVEF during the first 6 months after weaning and duration of HF are predictive for the outcome after LVAD removal in IDCM patients. Patients’ age, altered LV geometry, low wall motion velocity and prolonged LVAD support until improvement (> 6 months) appeared to be risk factors for HF recurrence.
Abstract 2910: Echocardiographic Indices For Diastolic Function Correlate to With The Collagen Content From Endomyocardial Biopsies In Patients With Heart Failure And Normal Ejection Fraction
Authors: Kasner Mario , Gaub Regina , Kallwellis-Opara Angela , Schultheiss Heinz P , Tschöpe Carsten
Published: July 2021

Background:
Morphologic charactheristics of the ventricle can influence the LV stiffness and therefore its diastolic function. We correlated diastolic parameters with collagen content from the endomyocardial biopsies (EMBs) in the patients with heart failure and normal EF.

Method:
We investigated 24 patients (51 ±10 years) with normal EF (65 ±8) and heart failure symptoms, whose endomyocardial biopsies (EMBs) were previously taken. Patients with coronary artery disease, valvular disease or atrial fibrillation were excluded. Total collagen content was determined using Sirius red staining. Collagen subtypes I and III were determined by standard immunohistochemistry methods in 19 patients. Assessment of diastolic function was performed by conventional Doppler (E/A, DT, IVRT), tissue Doppler measurements (E’/A’) and LV filling index E/E’.

Results:
Tissue Doppler parameters E’/A’ and E/E’ correlated strong with collagen content (r=-0.52, p=0.028 and r=0.50, p=0.040 respectively) and with collagen subtype I (r=-0.68, p=0.015 and r=0.66, p=0.018), whereas E/A (r= -0.34, p=0.078 and r=-0.28, p=0.268) and DT (r=0.22, p=0.093 and r=0.21, p=0.211) did not reach a statistical significance. Relaxation index IVRT correlated with collagen subtype I (r=0.62, p=0.014).

Conclusion:
Of all parameters tissue Doppler and LV filling index E/E’ correlated best with increased collagen content of endomyocardial biopsies in patients with heart failure and normal EF indicating induced cardiac remodelling process in those patients.
Abstract 2915: Circulating Fas in Subjects with Acute Cardiomyopathy and Myocarditis: Results from IMAC 1
Authors: Angheloiu George , Wright Dana M , Starling Randall C , Dec G. William , Torre-Amione Guillermo , Alexis Jeffrey , Sheppard Richard , Mann Douglas , McTiernan Charles , McNamara Dennis M
Published: July 2021

Introduction
In acute cardiomyopathy (ACM), lower myocardial Fas expression is predictive of greater LV recovery during follow up. Whether circulating Fas reflects myocardial activity and predicts recovery is unknown. We examined the predictive value of serum Fas, and its correlation with myocardial expression in subjects in the multicenter IMAC 1 (Intervention in Myocarditis and Acute Cardiomyopathy) trial.

Methods
Sixty-two subjects with recent onset dilated CM were enrolled in the IMAC 1 trial between 1996 and 1999. Plasma TNF, soluble TNF receptors 1 and 2, and serum Fas were measured (via ELISA) at entry in 56 subjects. In 20 subjects, myocardial expression of Fas was assessed by RNAse protection assay (RPA). Improvement in LVEF was assessed by radionuclide angiography at 6 and 12 months, and subjects were followed prospectively for up to 3 years. The correlation of serum Fas to circulating TNF and TNFR, and to myocardial Fas was assessed. The predictive value of serum Fas was assessed by comparison of Fas tertiles.

Results
The cohort (37M/25F, entry LVEF 0.25 ± 0.08, age 43 ± 12) had a mean serum Fas of 2.6 ± 1.4 ng/ml. Higher NYHA class was associated with higher Fas level (ng/ml): I/II/III/IV=2.4 ± 1.0/2.4 ± 1.1/2.7 ± 1.0/4.1 ± 2.9, p=0.035). Serum Fas demonstrated no correlation with myocardial Fas expression (r=0.169, p=0.50), but was tightly correlated with plasma TNF (r=0.75, p=0.001), TNFRI (r=0.73, p=0.001) and TNFRII (r=0.75, p=0.001). Examination of serum Fas tertiles demonstrate that low Fas was associated with higher RVEF at entry (0.39 ± 0.12 versus 0.31 ± 0.10, p=0.04), but not baseline LVEF (0.25 ± 0.08 versus 0.25 ± 0.09, p=0.97). Low Fas was associated with a trend toward higher improvement in LVEF at 12 months (change LVEF=0.19 ± 0.11, versus 0.12 ± 0.14, p=0.10) which failed to reach significance. Event free survival was similar in the low serum Fas and higher Fas tertiles (p=0.78).

Conclusion
Serum Fas was strongly correlated with plasma cytokines (TNF, TNFRI and TNFRII), NYHA class and RVEF. Serum Fas was not correlated with myocardial Fas, and Fas tertiles did not predict subsequent improved LVEF or event free survival. In ACM, serum Fas may reflect systemic peripheral inflammation rather than myocardial processes.
Abstract 2921: Genome-wide Association Reveals Sequence Variants on 4q25 that Affect the Risk of Atrial Fibrillation and Stroke
Authors: Gulcher Jeffrey , Gudbjartsson Daniel , Helgadottir Anna , Gretarsdottir Solveig , Arnar David , Thorleifsson Gudmar , Thorgeirsson Gudmundur , Hillert Jan , Ma Ronald , Rosand Jonathan , Ellinor Patrick , Holm Hilma , Thorsteinsdottir Unnur , Kong Augustine , Stefansson Kari
Published: July 2021

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in man and is characterized by chaotic electrical activity of the atria. It affects one in ten individuals over eighty, causes significant morbidity, and is an independent predictor of mortality. We have carried out a genome-wide scan using 316,000 SNPs on an Illumina beadchip to genotype a large atrial fibrillation cohort in Iceland. We found two common sequence variants (SNPs) within the same LD block on chromosome 4q25 near the PITX2 gene which increase the risk of AF substantially (by 1.72 and 1.39 per copy, respectively). An even higher risk was observed in individuals with typical atrial flutter. The association was replicated in Swedish, American, and Chinese populations. These variants do not associate with known risk factors for AF and thus provide an independent predictor of risk. The variants have a stronger effect in individuals younger than 80 but the risk in males and females is indistinguishable. As expected, given that AF is the primary cause of cardiogenic stroke, we found significant correlation to cardiogenic stroke in multiple cohorts. We have now followed up this initial study by combining these two variants to define a test to predict the risk of AF and show its characteristics in a meta-analysis of about 4500 AF patients from four European and American Caucasian cohorts. We demonstrate the effect of age on prediction. About 30% of the general population is positive for this test and has an OR of 1.8 for atrial fibrillation in individuals younger than 80. Such a test may be useful in recently diagnosed ischemic stroke and TIA patients to help decide which patients may benefit from ambulatory cardiac monitoring and perhaps provide a higher yield of detection of asymptomatic intermittent AF that is not discovered during the standard 24 to 48 hour monitoring within the hospital. This may be particularly important given that secondary stroke prevention strategies of antiplatelet agents and statins widely used for atherosclerosis-related strokes are much less effective for preventing strokes caused by AF.
Abstract 2942: Clinical Outcome in Patients with NonCalcified Coronary Plaque Detected by Multi Slice Computed Tomography: Risk Factors, Stenosis and 34-month Clinical Outcome.
Authors: Aggarwal Niti R , Knickelbine Thomas , Tande Aaron , Solftus Luke , Lesser John , Schwartz Robert S
Published: July 2021

Background:
Contrast enhanced Multislice Computed Tomography (MSCTA) can detect non-calcified plaque (NCP) in coronary arteries and associated coronary stenosis. However, the clinical impact of NCP is not well defined. This study examined the relationship of patient risk factors with NCP detected by MSCTA, and 34 month clinical follow-up.

Methods:
From September 2003 to June 2004, 506 patients underwent contrast MSCTA using a 16-slice CTA. Non-Calcified plaque (NCP) was defined as intraluminal density with 25 ≤ HU ≤ 130. 124 patients (25%) had coronary artery calcium scores of zero and complete conventional risk factor profiles. Of these, 111 patients were followed clinically for a mean of 34 months.

Results:
The CAC was zero in 124/506 (25%). Of these, 55/124 (44%) had no NCP, 63/124 (51%) had NCP but no significant stenosis, and 6/124 (5%) had NCP and stenosis by MSCTA. Patients in each group were similar in age, but differed significantly in their number of risk factors (Table 1

). Current or former smokers were more prevalent in the group with stenosis and NCP (83.3%) compared with the other two groups (41.3%, 16.4%), p=0.023.
Cardiac events at mean 34 month follow-up: No Plaque:
No events
NCP but no stenosis
: 2/54 (4%) with events (1 sudden cardiac death, 1 VT).
NCP with significant stenosis
: 2/ 5( 40%) pts had revascularization (1CABG, 1 PCI).

Conclusions:

Patients with NCP identified with MSCT had significantly more risk factors, especially smoking.

NCP without calcium can result in a significant coronary stenosis

NCP detected by MSCT in pts with a CAC of 0 identified patients with late cardiac events.
Abstract 2953: Myocardial Uptake of 7′(Z)-[
123
I]Iodorotenone During Vasodilator Stress in Dogs with Coronary Stenoses
Authors: Broisat Alexis , Ruiz Mirta , VanBrocklin Henry F , Goodman Norman C , Hanrahan Stephen M , Janabi Mustafa , Watson Denny D , Beller George A , Glover David K
Published: July 2021

There is a well recognized need for a new generation of SPECT perfusion tracers with improved myocardial extraction over a wide flow range. 7′(Z)-[
123
I]Iodorotenone (ZIROT) is a new myocardial perfusion imaging (MPI) agent with excellent myocardial uptake and favorable biodistribution. Our objective was to fully characterize the myocardial ZIROT extraction
vs
flow relationship during vasodilator stress in a large animal model. Accordingly, the adenosine A
2A
receptor agonist ATL-146e was infused i.v. (0.3 μg/kg/min) in 5 anesthetized, open-chest dogs with critical LAD stenoses. When LCx flow was maximal, 111 MBq (3mCi) of ZIROT and microspheres were co-injected and the dogs were euthanized 5 min later. The LV was divided into 4 short axis slices for
ex vivo
imaging followed by gamma well counting of myocardial segments. At the time of ZIROT injection, transmural flow in the stenotic LAD zone was similar to baseline (0.90 ± 0.22
vs
0.87 ± 0.11 ml/min/g, respectively P = NS), whereas normal LCx zone flow increased significantly (3.25 ± 0.51
vs
1.00 ± 0.17 ml/min/g, P<0.05). As shown, myocardial ZIROT extraction tracked regional myocardial blood flow better than either
201
thallium or
99m
Tc-sestamibi in our previous studies using a similar canine model. Furthermore, the ZIROT LAD/LCx activity ratios obtained by
ex vivo
imaging or gamma well counting (0.42 ± 0.08 and 0.45 ± 0.1 respectively) only slightly underestimated the LAD/LCx microsphere flow ratio (0.32 ± 0.09). The ability of ZIROT to more accurately track blood flow over a wide range makes it a very promising new MPI agent with potential for improved CAD detection and better quantitative estimation of the severity of flow impairment.
Abstract 2959: TGF-beta Is A Promising Biomarker For Monitoring The Aortic Root Dilatation And Losartan Therapy In Marfan Syndrome
Authors: Matt Peter , Habashi Jennifer , Holm Tammy , Klein Erin , Gamradt Matt , Zerkowski Hans-Reinhard , Carrel Thierry , Huso David , Van Eyk Jennifer , Dietz Harry
Published: July 2021

Objectives: Aortic root dilatation is the main cause of morbidity and mortality in Marfan syndrome (MFS), a disorder caused by mutations in the gene encoding fibrillin-1 and consequent dysregulation of TGF-beta signaling. The aim of this study was to discover a serological biomarker for the aortic root dilatation in a mouse model of MFS, that was also responsive to losartan therapy.

Methods: Serum samples from mice heterozygous for a fibrillin-1 missense mutation (C1039G/+) and wild-type mice treated with losartan or placebo were obtained at 10 weeks, 6 months and 10 months of age. Total (acid activated) TGF-beta 1 serum concentrations were measured by ELISA. Echo measurements of the aortic root were obtained from a parasternal long axis view at 10 months of age.

Results: Mean TGF-beta serum concentrations were higher in C1039G/+ mice compared to wild-type mice (p=0.01; 80.0 ng/ml (n=5) vs. 58.3 ng/ml (n=4) at 10 weeks, 117.4 ng/ml (n=11) vs. 87.0 ng/ml (n=6) at 6 months, 137.5 ng/ml (n=3) vs. 103.0 ng/ml (n=2) at 10 months, respectively). Losartan-treated C1039G/+ mice had significantly lower mean TGF-beta serum levels compared to C1039G/+ mice with placebo (p=0.007; 92.9 ng/ml (n=5) vs. 117.4 ng/ml (n=11) at 6 months, 101.2 ng/ml (n=13) vs. 137.5 ng/ml (n=3) at 10 months, respectively). Mean TGF-beta serum concentrations in losartan-treated C1039G/+ mice and wild-type mice with placebo were not significant different (p=0.3; 92.9 ng/ml (n=5) vs. 87.0 ng/ml (n=6) at 6 months, 101.2 ng/ml (n=13) vs. 103.0 ng/ml (n=2) at 10 months, respectively). Echo analyses revealed significantly smaller mean aortic root diameters in 10 months old wild-type and losartan-treated C1039G/+ mice compared to age-matched C1039G/+ mice with placebo (p=0.001; 1.94 mm (n=2) and 2.06 mm (n=13) vs. 2.4 mm (n=3), respectively).

Conclusions: TGF-beta serum levels are higher in C1039G/+ mice compared to wild-type mice. Losartan treatment of C1039G/+ mice reduces TGF-beta serum concentrations and aortic root diameters towards wild-type levels. Serum TGF-beta is a promising biomarker for prognostication and monitoring the therapeutic response to losartan therapy in Marfan syndrome.
Abstract 2961: Ventricular Stiffness Contributes to Hypertension in Patients with Clinical Science Repaired Coarctation of the Aorta
Authors: Senzaki Hideaki , Ishido Hirotaka , Masutani Satoshi
Published: July 2021

Background

Despite successful repair, patients with coarctation of the aorta (CoA) often show persistent hypertension at rest and/or during exercise. Previous studies indicated that this phenomenon is mainly due to abnormality in arterial bed and its regulatory system. However, blood pressure is determined not only by the state of arterial bed but also by cardiac function to which the blood vessels are coupled. We hypothesized that ventricular stiffness contributes to the hypertensive state in patients with repaired CoA, in addition to increased vascular stiffness.

Methods and Results

The left ventricular pressure-area relationship was measured invasively in 37 patients (2–14 years of age) with successfully repaired CoA (defined as 0 mmHg pressure gradient) and compared with that of 41 age-matched control subjects who had small ventricular septal defect with an estimated shunt ratio <5%. Data recorded at rest and during transient preload reduction by inferior vena caval obstruction yielded left ventricular chamber stiffness (Ees) and effective arterial stiffness (Ea). The mean systolic blood pressure (SBP) was significantly higher in CoA patients (118±24 mmHg) than in the control (98±9 mmHg, p<0.01). Ees (45±19 mmHg/mlm
2
) and Ea (36±19 mmHg/mlm
2
) of CoA patients were significantly higher than those of the controls (18±7 and 20±7 mmHg/mlm
2
, respectively, P<0.001). To quantify the contribution of increased ventricular stiffness to the high SBP in CoA patients, SBP was estimated by assuming that Ees of CoA patients was equal to the mean Ees value of the control. The results showed a significant decrease in blood pressure by 12±5 mmHg, indicating that ventricular stiffness accounts for about 60% of the elevated blood pressure in CoA patients.

Conclusions

Increased ventricular stiffness greatly contributes to elevated systolic pressure in patients with repaired CoA. Thus, in addition to the recognized arterial stiffness, abnormal neurohumoral activity and autonomic dysfunction, ventricular stiffness could be a viable target for reduction of blood pressure and improvement of prognosis of patients with this disease.
Abstract 2978: Long-Term Results After Unprotected Left Main Stenting With Drug-Eluting Stents. Insights From the French Left Main Taxus Registry
Authors: Vaquerizo Beatriz , Lefèvre Thierry , Darremont Olivier , Silvestri Marc , Routledge Helen , De Marco Federico , Dumas Pierre , Ohanessian Alice , Morice Marie-Claude , Garot Philippe
Published: July 2021

Drug-eluting stents (DES) have reduced restenosis rate and are now emerging as an alternative to bypass surgery (CABG) for treating unprotected left main (ULM) stenosis. A prospective registry was set up in France to explore the role of DES in this setting. Consecutive patients (Pts) with de novo ULM stenosis undergoing PCI with Paclitaxel eluting stent (PES) in 4 French centers were prospectively included in this real world study. Acute MI and cardiogenic shock were the only criteria for exclusion. Pts had a loading dose (450 to 600 mg) of plavix before the procedure, aspirin (≥75 mg) and plavix (75 to 150 mg/day) for at least 6 months. Clinical outcome was planned up to 3 years and repeat angiography was strongly recommended at 6 months. Between March 2003 and June 2005, 291 Pts were included: 69±11 yrs old, 77% male, 29% diabetic, 5% renal failure, 17% previous or recent MI, 38% acute coronary syndrome and 25% 3-vessel disease. Euroscore was 4.8±3.4 (predicted in-hospital mortality in case of CABG 6.3±10.4). Provisional T stenting (distal LM in 78.4%) was used in 92% of cases and final kissing balloon in 96.8%. Angiographic success was obtained in 99.7%. Other lesions (1.2±0.9) were treated during the same hospitalization in 77%. Repeat angiogram was performed in 182 Pts (63%) at 7.0±4.0 months. Restenosis was observed in 8.7%. The clinical outcome is summarized below: By multivariate analysis Euroscore (OR 1.245; 95% CI 1.077–1.439; p=0.003), terminal renal failure with dialysis therapy (OR 0.018; 95% CI 0.002– 0.172; p=<0.001) and LM bifurcation angle T-type (OR 0.205; 95% CI 0.071– 0.593; p=0.003) were the only independent predictors of death. The incidence of definite or probable LM stent thrombosis (ST) as defined by the ARC was at 2-years 2.09% (3 early ST and 3 late or very late ST). LM stenting using PES with a strategy of provisional side branch T stenting in case of distal lesion provides excellent acute angiographic results and very acceptable long-term outcome.
Abstract 3001: Assessment Of Ethnic Differences In The Left Ventricular Remodelling In Elite Athletes
Authors: Basavarajaiah Sandeep , Carby Lorna , Yavari Arash , Nandagudi Anupama , Jackson Gordon , Whyte Gregory , Shah Ajay , Sharma Sanjay
Published: July 2021

Objectives:

The upper limits of physiologic increase in the left ventricular (LV) dimensions for the purposes of differentiation from cardiomyopathies are well established in Caucasian athletes. However, there are few data regarding the physiologic LV remodelling in black athletes (BA) in whom deaths from cardiomyopathies are more prevalent.

Methods:

Between 2005 and 2006, 200 asymptomatic and normotensive black (African/AfroCaribbean) male athletes (mean age: 20.5 ± 5.80; range 14 –35 years and a mean BSA: 1.94 ± 0.16 m
2
; range1.36 –2.29) underwent 12-lead EKG and 2-D echocardiography. The results were compared to those of 100 black controls (BC) and 200 highly trained white male athletes matched for age, size, sport and training programs. None of them had a family history of cardiomyopathy. Cardiac dimensions and function were measured in accordance using conventional methods.

Results:

The LV dimensions of black athletes (BA) compared with black controls (BC) and WA are shown below
Data expressed as mean
±
standard deviation (range) LVWTd- left ventricular wall thickness in end diastole LVIDd- left ventricular internal dimensions in end diastole
Both BA and WA had a greater LV dimensions than BC. Black athletes had greater LVWT than WA amounting to a difference of 11%. In absolute terms, 40 (20%) BA had a LVWT > 12 mm compared with 12 (6%) WA. There were no significant differences in the LV cavity size or indices of diastolic function between BA and WA. All BA with a LVWT > 12 mm had an enlarged LV cavity size and normal indices of diastolic function indicating physiologic left ventricular hypertrophy (LVH) rather than hypertrophic cardiomyopathy (HCM).

Conclusion:

•Black athletes develop modest increase in the LV dimensions as compared to BC. •The magnitude of LVH in BA is significantly greater than in WA. •More BA have absolute LVWT values in the region compatible with morphologically mild HCM. •Our study calls for a separate physiologic upper limits for LV dimensions in BA.
Abstract 3009: Major Subgroup Analyses from the FINESSE Trial: Evaluation of Abciximab + Half -Dose Reteplase, Abciximab Alone, or Placebo for Facilitation of Primary PCI for ST Segment Elevation MI
Authors: Tendera Michal , Katedra Klinika I , Ellis Stephen G , van Boven A.J. , de Belder Mark A , Montalescot Gilles , Widimsky Petr , Janssens Luc , Andersen H.R. , Adamus Jerzy , Peruga Jan Z , Kosimder Maciej , Betriu Amadeo , Armstrong Paul , Brodie Bruce , Herrmann Howard C , Barnathan Elliot S
Published: July 2021

Introduction:
Whereas primary PCI is the preferred reperfusion strategy for acute ST elevation MI if performed promptly, treatment delays are common.

Methods:
We tested the hypothesis in a randomized placebo-controlled double-blind trial of 2452 subjects from 20 countries that early pharmacologic therapy with half dose reteplase and abciximab, followed by PCI would improve the outcome in ST elevation MI patients presenting within 6 hours of symptom onset with anticipated first medical contact to catheterization time of 1– 4 hours, relative to patients receiving abciximab at the time of primary PCI; with a third randomized arm of early abciximab to better evaluate the contribution of reteplase to the combination therapy. The primary study endpoint was a composite of all cause mortality, ventricular fibrillation beyond 48 hours, cardiogenic shock or heart failure requiring re-hospitalization or an emergency room visit within 90 days. A major secondary endpoint was % ST segment resolution (>70%) 60 –90 min after randomization. Final patient enrollment was completed December 30, 2006, and 90 day follow up results will be available fall 2007.

Results:
Enrollment demographics are as follows: mean age = 62 years (16% ≥75), 26% female, 10% Killip II-IV, 11% prior MI, 16% diabetics, 48% anterior MI and 61% enrolled ≤ 3h after symptom onset. The median times from symptom onset to randomization, and randomization to first balloon inflation by tertiles were 1.5, 2.6, and 4.4 hours and 1.2, 1.8, and 2.6 hours, respectively. Pre specified subgroup analyses for the primary and major secondary study endpoints included time from symptom onset to randomization (≥3 vs >3 hours), randomization time to first balloon inflation (by tertiles), Killip Class (I vs II-IV), gender, age (<75 vs ≤75 years), history of prior MI, diabetes, and anterior vs non-anterior MI.

Conclusion:
The findings from these analyses will supplement the primary study results from this, the largest randomized trial of facilitated angioplasty, to help define the proper management of this important group of high-risk patients.
Abstract 3060: Wrap Tightness Determines Rate and Degree of Reverse Ventricular Remodeling with Ventricular Restraint Therapy
Authors: Ghanta Ravi K , Rangaraj Aravind , Umakanthan Ramanan , Lee Lawrence , Tabata Minoru , Laurence Rita G , Fox John A , Bolman R. M , Cohn Lawrence H , Chen Frederick Y
Published: July 2021

Objective:
We have developed an adjustable and measurable technique of ventricular restraint by placing a fluid-filled epicardial balloon around the entire ventricular surface. Wrap tightness is quantified by measuring balloon luminal pressure at end-diastole. In this study, the effect of wrap tightness on reverse remodeling in a chronic ovine model of HF was assessed.

Methods:
HF developed in 9 ovine 2 months after ligation of diagonal coronary arteries. Ovine were divided into 3 equal groups: control, low restraint (1.5 mmHg), and high restraint (3.0 mmHg). Epicardial balloons were implanted and ventricular remodeling was evaluated over 2 more months with weekly echocardiography. Wrap tightness was measured weekly via a portacath. Change in LV EF, EDV, and wrap tightness was then assessed using repeated measures analysis of variance.

Results:
Ventricular restraint decreased EDV and improved EF in all HF ovine. High restraint decreased EDV to a greater degree than low restraint. Wrap tightness decreased as the heart reverse remodeled. Reverse remodeling slowed. Peak reverse remodeling occurred after 21 days with high restraint and after 35 days with low restraint.

Conclusion:
Ventricular restraint wrap tightness affects the rate and degree of improvement in LV EDV. Periodic adjustment of wrap tightness may be required for optimal restraint therapy efficacy.
Abstract 421: Injection Of Self-assembled Nanopeptides With Clonal Cardiac Sca-1 Positive Cells Improve Cardiac Function After Myocardial Infarction
Authors: Tokunaga Masakuni , Nagai Toshio , Iwanaga Koji , Matsuura Katsuhisa , Takahashi Toshinao , Noguchi Tomohiro , Wang Ping , Liu Mei Lan , Oyama Tomomi , Kanda Masato , Komuro Issei
Published: July 2021

Biological scaffolds have been reported to offer microenvironment for the transplanted cells, support the cell survival and maintain the release of paracrine factors. However, it is still unknown what kinds of cell sources, scaffolds and their delivery methods are suitable for myocardial repair. Self-assembled nanopeptides, Puramatrix (PM), have been reported to be superior to the other scaffolds in terms of its animal free origin, biodegradability and non-immunogenic properties, which are prerequisite for the clinical application. To examine whether cell transplantation with PM can restore the cardiac function of C57BL/6 mouse myocardial infarction (MI) models, we injected the cell-PM complex into the peri-MI area and then overlay a thick hydrogel patch on the MI area. The mice were divided into following groups according to the transplanted cell types and matrices; bone marrow mononuclear cells with PM (BM/PM), clonal Sca-1 positive cardiac progenitors with PM (cSca-1/PM) and PM alone (PM). Non-treated MI models (Cont) were prepared as controls. Infarct area was examined by Masson trichrome staining and cardiac dimension and function were examined by echocardiography two weeks after transplantation. cSca-1/PM and PM attenuated ventricular enlargement in comparison with BM/PM and Cont (left ventricular diastolic dimension: cSca-1/PM 4.9 ± 0.6 mm, PM 5.3 ± 1.0 mm, BM/PM 6.6 ± 0.1 mm, Cont 6.1 ± 0.1 mm). Fractional shortening of cSca-1/PM and PM were higher than that of BM/PM and Cont (cSca-1/PM 14 ± 3.2%, PM 13 ± 2.3%, BM/PM 8.0 ± 2.5%, Cont 9.9 ± 3%). Infarct area of cSca-1/PM was smaller than that of BM/PM, PM and Cont (cSca-1/PM 36 ± 12%, BM/PM 50 ± 3.1%, PM 53 ± 18%, Cont 57 ± 4.0%). To elucidate the mechanisms of the beneficial effects of cSca-1/PM complex on the infarct area, the number of CD31 positive capillary was examined by immunohistochemical method. Capillary density in the infarct area of cSca-1/PM was higher than that of PM (cSca-1/PM 15%, PM 8%). In summary, transplantation of cSca-1 in combination with PM prevents cardiac remodeling, improves cardiac contraction and reduces infarct area partially through angiogenesis. Cell therapy with PM may enable us to circumvent the current problem in the efficiency of tissue engineering-based cell therapy.
Abstract 3119: Long-term Safety of Cilostazol in Patients With Peripheral Artery Disease
Authors: Hiatt William R , Brass Eric P , Money Sam
Published: July 2021

Cilostazol, a phosphodiesterase III inhibitor, is indicated to treat the symptoms of claudication in patients with peripheral arterial disease (PAD). At the time of approval the FDA required an additional long-term safety study to evaluate cilostazol’s effect on mortality. Subjects (n=1899) with a clinical diagnosis of PAD and symptoms of claudication were screened for a randomized, double blinded, placebo-controlled safety study of cilostazol. The modified intent-to-treat (mITT) population (n=1435) included all randomized patients who received at least one dose of study medication and includes follow up of more than 30 days after discontinuation of study drug. A total of 717 patients received cilostazol and 718 received placebo. Cilostazol was administered at a primary dose of 100 mg twice daily. Long-term adherence to study medication was poor with over 60% of participants discontinuing therapy by 36 months. Therefore the mortality analysis focused on deaths during the period on-treatment defined as the period during which study drug was taken plus a 30-day post-dosing follow up period. Total patient-years exposure on-treatment for cilostazol was 1046 and on placebo was 1090. On-treatment there were 18 deaths on cilostazol and 19 deaths on placebo for a hazard ratio of 0.99 (95% confidence interval 0.52 to 1.88). Cardiovascular deaths on-treatment occurred in 14 patients on cilostazol and 14 on placebo. In the full mITT population at 36 months, there were 101 deaths, 49 on cilostazol and 52 on placebo with hazard ratio of 0.94 (0.64 –1.39). Thus most deaths occurred more than 30 days after study drug discontinuation. Serious bleeding events affected 18 patients on cilostazol and 22 on placebo in the on-treatment population. Bleeding events were similar in patients also taking aspirin, aspirin plus clopidogrel or anticoagulants over the course of the study. This long-term study demonstrated no safety signal for cilostazol on all cause or cardiovascular mortality. However the study was under-powered to detect a small adverse impact of cilostazol on mortality (hazard ratio upper bound of the 95% confidence interval 1.88 in the on-treatment population). Serious bleeding events appeared not to be increased by cilostazol.
Abstract 3144: Prevalence Of Insulin Resistance Among Non-diabetic Chronic Heart Failure Patients And Its Relation To Disease Severity
Authors: Lang Chim C , ALZadjali Matlooba A , Godfrey Valerie , Choy AnnaMaria , Khan Faisel , Struthers Allan D
Published: July 2021

Body:

Background Purpose-

There is increasing evidence of a reciprocal interrelationship between chronic heart failure (CHF) and insulin resistance (IR) such that IR may be pathophysiologically linked to the evolution of the disease in CHF. However, the prevalence of IR in the CHF population has not been fully defined. The purpose of this study was to establish the prevalence of IR among non-diabetic CHF patients and to assess its relation to disease severity.

Methods-

The homeostatic model of insulin resistance (HOMA-IR) was assessed in a cohort of 129 CHF patients; mean age (69.2±10.4 yrs) [range 30 –90 yrs], males 76%, CHF of ischemic etiology 82.2% and BMI (27.4±4.4kg/m2). All were on regular CHF medication. Patients underwent cardiopulmonary exercise testing and peripheral endothelial function testing by reactive hyperemia peripheral arterial tonometry (RH-PAT).

Results-

Prevalence of IR as defined by Fasting Insulin Resistance Index >2.7 was 61% in CHF and was significantly higher than in the 23 subjects who were coronary artery disease controls without HF(P<0.05). The degree of IR was not related to the etiology of CHF. There was a significant correlation between IR and serum triglyceride (r = 0.333, P<0.01), HDL cholesterol (r = − 0.275, p<0.05), impaired fasting glucose (r = 0.358, P<0.01) and central obesity (r = 0.232, p<0.01). The degree of IR was related to the exercise capacity and peak oxygen consumption (VO
2
). Mean of IR increased significantly with worsening functional NYHA Classes I, II, III and IV [2.1, 2.9, 4.8, 8.9], (r = 0.437, p<0.01). The IR patients had a significantly lower exercise duration (340 ±168.3 vs. 601 ±265.9 s, p< 0.01) and peak VO
2
(6.4 ± 2.3 vs. 14.5 ±1.7 ml/kg per min, p< 0.05). Exercise peak cardiac output determined by the inert gas re-breathing method was lower in patients with IR (5.2 ±1.2 vs. 9.2 ± 0.89 l/min, p<0.05). Endothelial function as measured by RH-PAT decreased significantly in patients with IR compared to the patients with normal insulin sensitivity (1.64 ± 0.36 vs. 2.0 ± 0.53, p<0.05I).

Conclusion -

These findings suggest that IR is highly prevalent among CHF patients and is associated with decreased exercise effort and capacity in patients with CHF. Targeting IR might represent a new strategy in the treatment of CHF.
Abstract 3164: Angioscopic Findings of Sirolimus-Eluting Stent for Acute Myocardial Infarction: An Intermediate-term Follow-up Study
Authors: Dai Kazuoki , Ishihara Masaharu , Inoue Ichiro , Kawagoe Takuji , Shimatani Yuji , Kurisu Satoshi , Nakama Yasuharu , Maruhashi Tatsuya , Kagawa Eisuke , Aokage Toshiyuki , Ikenaga Hiroki
Published: July 2021

Background:
Sirolimus-Eluting Stent (SES) is effective in reducing restenosis. Although several studies have reported the usefulness of SES in patients with acute myocardial infarction (AMI), the current major concerns of the use of SES in AMI are over-suppression of neointimal formation and late thrombosis. Coronary angioscopic examination provides an opportunity to assess neointimal coverage over stent and adherent thrombus in patients.

Method:
This study consisted of 18 patients who underwent primary angioplasty with SES for AMI. A mean average of 7.6 ± 2.5 months after SES implantation, coronary angioscopic examination was performed. Neointimal coverage of the SES was assessed by the grading as: grade 0 = complete exposure of the stent struts, grade 1 = dull light reflex from stent struts, grade 2 = no light reflex, but slightly visible stent struts, and grade 3 = complete coverage. Because the grade of neointimal coverage may vary from struts to struts, both maximum and minimum grade of neointimal coverage were assessed. The presence of thrombus was also evaluated.

Results:
All but one patient had at least 2 different grades of neointimal coverage; one patient had only grade 0. When the maximum grade of neointimal coverage was assessed, grade 0 was observed in 1 patient, grade 1 in 4 patients, grade 2 in 8 patients, and grade 3 in 5 patients. As to minimum grade, grade 0 was observed in 11 patients and grade 1 in 7 patients, however, grade 2 and 3 was not observed. Thrombus adherent to uncovered stent struts (grade 0 or 1) was observed in 8 patients (44%).

Conclusion:
The process of neointimal coverage over SES was heterogeneous. Even 7 months after SES implantation for AMI, most of the stent struts were not covered by neointimal with high incidence of adherent thrombus. Long-term aggressive anti-platelet therapy should be advocated for patients with AMI who were treated with SES.