bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 3171: Chordal Cutting to Relieve Mitral Leaflet Tethering Diminishes LV Remodeling Following Chronic Inferior Myocardial Infarction
Authors: Messas Emmanuel , Bel Alain , Szymanski Catherine , Cohen Iris , Handschumacher Marc D , Trinquart Ludovic , Desnos Michel , Carpentier Alain , Menasché Philippe , Hagège Albert A , Levine Robert
Published: July 2021

Background.
We have previously demonstrated that severing two second-order chordae to the anterior mitral leaflet (AL) in sheep does not adversely affect LV size and function acutely.

Objectives.
This study tested whether chordal cutting exacerbates long-term LV remodeling when applied to treat ischemic mitral regurgitation (MR) in a chronic myocardial infarction (MI).

Methods.
A posterolateral MI was created in 18 sheep by ligation of obtuse marginal branches. After chronic remodeling and MR development at 2 months, sheep were randomized to sham surgery versus anterior leaflet (AntL) or bileaflet (BiL) second-order chordal cutting (n=6 each), techniques in clinical application. 2D and 3D echo at baseline, chronic infarction (2 months), and follow-up at a mean of 6.5 months post-MI (sacrifice) measured LV end-diastolic and end-systolic volume (EDV and ESV), ejection fraction (EF), wall motion score index (WMSi), and posterior leaflet (PL) restriction angle relative to the annulus.

Results.
All measurements were comparable among groups at baseline and chronic MI. At sacrifice, AntL and BiL chordal cutting limited the progressive remodeling seen in controls. LVESV increased by 33.0±7.2% and 28.0±5.0% relative to chronic MI with AntL and BiL chordal cutting, versus 109.0±8.7% in controls (p<0.01) (LVESV=60.6±5.1ml vs 61.8±4.1ml vs 82.5±2.6ml in controls). LVEDV increased by 26.0±5.5% and 22.0±3.4% with AntL and BiL chordal cutting, versus 63.0±2.0% in controls (p<0.01). LVEF and WMSi were not significantly different at follow-up among chordal cutting and control groups. MR progressively increased to moderate in controls but decreased to trace-mild (vena contracta ≤2mm) in 83% of chordal cutting sheep. BiL chordal cutting provided greater PL mobility (decreased PL restriction angle to 54±5° versus 93±3° with AntL chordal cutting, p<0.01).

Conclusions:
Cutting secondary chordae in the chronic post-MI setting does not adversely affect long-term LV remodeling, and limits progressive increases in LV volumes.
Abstract 3183: Clinical Utility of 3-Dimensional Echocardiography in Evaluation of Severe Tricuspid Regurgitation Caused by Pacemaker or Implantable Cardioverter-Defibrillator Leads
Authors: Seo Yoshihiro , Ishizu Tomoko , Nakajima Hideki , Uno Kiyoko , Kawamura Ryou , Sekiguchi Yukio , Watanabe Shigeyuki , Yamaguchi Iwao , Aonuma Kazutaka
Published: July 2021

Background. Pacemaker or implantable cardiovascular-defibrillator (ICD) leads may be a primary cause of symptomatic tricuspid regurgitation (TR). The aim of this study was to evaluate the utility of 3-dimensional echocardiography (3-DE) in identifying intracardiac routes of pacemaker or ICD leads in relation to TR. Methods. 3-DE examinations were performed to evaluate intracardiac lead routes from right atrium to ventricle and positions at the tricuspid valve in 73 patients: 53 patients with pacemaker and 20 patients with ICD. TR severity was assessed by 2-dimensional echocardiography and classified as mild, moderate, or severe based on the ratio of TR area to right atrium area. Results 3-DE identified the lead route and position at the tricuspid valve in 68 patients (93.1%). In the remaining 5 patients, an appropriate image could not be obtained due to artifacts caused by the lead. TR severity was classified as mild in 47 patients, moderate in 18 patients, and severe in 8 patients. In 7 of the 8 patients with severe TR, obstruction to tricuspid valve closing caused by the lead was identified (Figure

): obstruction of septal leaflet in 3 patients, posterior leaflet in 3 patients, and anterior leaflet in 1 patient. However, in all patients with mild to moderate TR, the lead was positioned at the annulus side between leaflets, and no closing obstruction was identified. Conclusion. 3DE can identify pacemaker or ICD lead route and position at the tricuspid valve and the obstruction to closing caused by the lead in patients with severe TR. Therefore, 3DE may be useful to evaluate the cause of severe TR in patients receiving a pacemaker or ICD.
Abstract 3189: Prevalence of Bicuspid Aortic Valve in Turner Syndrome
Authors: Sachdev Vandana , Matura Lea Ann , Sidenko Stanislav , Ho Vincent , Arai Andrew , Rosing Douglas R , Bondy Carolyn
Published: July 2021

Women with Turner syndrome (TS) have an increased risk of congenital cardiovascular defects. Previous studies have reported a 10 –20% prevalence rate of bicuspid aortic valves and there are increasing reports of a vasculopathy that predisposes patients to aortic dilatation and dissection. This prospective study aimed to characterize aortic valve and aortic root structure in unselected asymptomatic individuals with TS. A total of 253 females aged 7– 67 years with karyotype proven TS were examined. Transthoracic echocardiography revealed a normal tricuspid aortic valve (TAV) in 162, a ‘probable TAV’ in 8 subjects, a bicuspid aortic valve (BAV) in 65 and ‘probable BAV’ in 3 subjects. The aortic valve could not be visualized by echocardiography in 15/253 or 6%. Magnetic resonance imaging (MRI) revealed valve structure in 11/12 of the probable cases (all confirmatory of the ‘probable’ diagnosis) and 12/15 of the non-visualized cases (8 BAV and 4 TAV), so only 3/253 subjects could not be visualized by either modality. The aortic valve was bicuspid in 76 of the 250 adequately imaged subjects (30%). Peak aortic valve flow was higher in BAV subjects (1.72±0.07 vs. 1.90v0.03 m/sec, P=0.0002), with one case of significant aortic stenosis. Among subjects with a BAV, aortic regurgitation was moderate or greater in ∼15%. Aortic diameters at the annulus, sinuses of Valsalva, sinotubular junction and ascending aorta were all significantly greater in the BAV group. Thirty patients in the BAV group (12%) had aortic root diameters that were outside of the 95% normal confidence limits based on Roman nomograms. Ascending aortic diameters by echo and MRI were highly correlated (r=0.77). In summary, echocardiography supplemented with MRI reveals an extraordinarily high prevalence of abnormal aortic valves in asymptomatic subjects with TS. The abnormal valve structure is associated with higher peak flows, evidence of clinically significant valvular dysfunction, and widening of the ascending aorta in a significant number of patients. All girls and women with TS should have careful echocardiographic evaluation upon diagnosis to identify the one in three asymptomatic individuals with an abnormal valve requiring monitoring for aortic root dilatation and valvular dysfunction.
Abstract 3216: The Serum of Pexelizumab-Treated ST-Segment Elevation MI Patients Reduces Complement Activation but not Cell Apoptosis
Authors: Martel Catherine , Theroux Pierre , Labarthe Benoit , Rivard Jacinthe , Bonnefoy Arnaud , Granger Christopher B , Armstrong Paul W
Published: July 2021

Objective
: Complement (C) activation and apoptosis are involved in the pathophysiology of STEMI. Why C inhibition with Pexelizumab (PEX) in the APEX-AMI failed to reduce mortality in STEMI pts undergoing primary PCI is unclear. We therefore examined C activation and cell apoptosis in the serum of APEX pts in a model of human umbilical vein endothelial cells (HUVEC).

Methods
: Batch analyses of pre-prepared frozen serum of 45 patients from a single center obtained before initiation of PEX and 24h later before drug discontinuation were performed. An amount of 500 μl serum was added to 2 ml endothelial basal medium in HUVEC culture for 72-hour at 37°C, 5% CO
2
and 95% humidity. C4a, C3a, Bb, and MBL of proximal C, and C5a and sC5b-9, the soluble inactive form of C5b9 from the terminal C, were assessed in supernatants by CBA and ELISA assays. HUVEC-bound C5b-9, the membrane attack complex (MAC), was measured by flowcytometry. Apoptosis was quantified as % of HUVEC with DNA fragmentation after permeabilization and cells positive to annexinV and/or propidium iodide (PI). Analyses were performed blinded to treatment allocation.

Results(Table

)

: Basal levels of all parameters were similar in PEX (n=24) and placebo (n= 21) groups. Proximal C remained unchanged at 24 hours and unaffected by PEX. C5a, sC5b-9, and MAC all significantly increased at 24 hours in the placebo group, but were strikingly inhibited by PEX. MAC elevation correlated with C4a (r=0.322,
p
=0.004), C5a (0.468,< 0.0001), sC5b-9 (0.490,< 0.0001), and with apoptotic cell numbers by DNA fragmentation (0.449,<0.0001). Despite this, PEX had no detectable effects on apoptosis.

Conclusions
: In this cell culture model, the serum of STEMI pts containing PEX almost completely inhibited terminal C while preserving proximal C. Why this did not translate into clinical benefit remains to be elucidated. The absence of effect on apoptosis suggests that C activation in PCI-reperfused STEMI is more a consequence than a cause of apoptosis.
Abstract 3240: High Speed Rotational Coronary Venous Angiography Improves Delineation of Coronary Venous Anatomy during Cardiac Resynchronization Therapy
Authors: Kofune Masayoshi , Watanabe Ichiro , Ashino Sonoko , Okumura Yasuo , Kawauchi KIazunori , Kofune Tatsuya , Ohkubo Kimei , Hashimoto Kenichi , Shindo Atsushi , Sugimura Hidezou , Nakai Toshiko , Saito Satoshi , Hirayama Atsushi
Published: July 2021

Background: The implantation of the left ventricular lead for biventricular devices can be challenging due to anatomic variation in the branching pattern of the coronary sinus (CS). Standard coronary venous (CV) angiography (SCVA) provides a static, fixed projection of the CV tree. Typically multiple contrast injections are obtained to gain a better understanding of vessels overlap and foreshortening. But, even in this situation, the site of side branch takeoff, its angulation and course cannot be reliably predicted - particularly in the presence of complex branching patterns. High-speed rotational CV angiography (RCVA) permits a dynamic, multi angle visualization of the CV anatomy.

Objective: To compare RCVA with SCVA during cardiac resynchronization therapy.

Methods: Digitally acquired RCVA from 10 patients were analyzed. RCVA uses a rapid isocentric rotation over a 180° arc, RAO 54° to LAO 54° in 4 sec, acquiring 121 frames /angiogram with a single injection of 20 ml of contrast (Infinix, Toshiba). The CV anatomy assessed by RCVA was compared with 2 static perpendicular views: RAO 45° and LAO 45°.

Results: Three-dimensional models of the venous tree were reconstructed (Figure

), and the rotational images were analyzed using a full range of gantry angles, providing the operator with considerably more information about the CV anatomy than SCVA images.

Conclusion: RCVA provides a better understanding of the CV anatomy and the special relationship of its branches. The SCVA view which optimally displayed the appropriate CS branch for left ventricular lead implantation was often different from the conventional RAO and LAO views.
Abstract 3241: Long-TermSurvival after Coronary Artery Bypass versus Percutaneous Coronary Intervention with Bare Metal Stent Implantation in Patients with Diabetic Retinopathy
Authors: Ohno Takayuki , Suematsu Yoshihiro , Motomura Noboru , Ono Minoru , Fujita Hideo , Ando Jiro , Morita Toshihiro , Hirata Yasunobu , Takamoto Shinichi
Published: July 2021

Background
: Coronary heart disease is the leading cause of death in diabetic population. Compared with diabetics without retinopathy, diabetics with retinopathy have an increased risk of myocardial infarction and death from coronary heart disease. Therefore, it is crucial to select an appropriate revascularization method in this considerable high-risk group.

Methods:
Between 1996 and 2004, a total of 149 patients with diabetic retinopathy underwent revascularization, either coronary artery bypass surgery (CABG) (n=56) or percutaneous coronary intervention with bare metal stents (BMS) (n=94). We compared overall survival rates of the two methods. Mortality was estimated according to Kaplan-Meier methods and was compared using the log-rank test.

Results:
The average follow-up from the time of the initial revascularization was 59.7 ± 33.3 months. During the entire follow-up, there was 8(14.5%)death in the CABG group and 27(28.7%) deaths in the BMS group. The average duration between death and revascularization was 81.3 ± 24.6 for the CABG group and 29.9 ± 23.8 for the BMS group (P<0.001). The 6-year overall survival was 94.8% for the CABG group and 73.6% for the BMS group. Mortality curves differed significantly between the two groups (P=0.004) (Figure

). After adjustment for baseline characteristics including age, sex, HbA1c, insulin, serum creatinine, ejection fraction, and the extent of coronary disease, the hazard ratio of death afforded by CABG was 0.36 (95% confidence interval, 0.15–0.87; P=0.023).

Conclusions:
In patients with diabetic retinopathy, CABG conferred survival benefit over BMS implantation.
Abstract 3248: Is It Safe to Train Residents to Perform Cardiac Surgery? Intermediate Term Follow-up
Authors: Martin Billie Jean , Kalavrouziotis Dimitri , Baskett Roger
Published: July 2021

Introduction
While there are rigourous assessments made of trainees’ knowledge through formal examinations, objective assessments of technical skills are not available. Little is known about the safety of allowing resident trainees to perform cardiac surgical operations.

Methods
Peri-operative date was prospectively collected on all patients who underwent coronary artery bypass grafting (CABG), aortic valve replacement (AVR) or a combined procedure between 1998 and 2005. Teaching-cases were identified by resident records and defined as cases which the resident performed skin to skin. Pre-operative characteristics were compared between teaching and non-teaching cases. Short-term adverse events were defined as a composite of: in-hospital mortality, stroke, intra- or post-operative intra-aortic balloon pump (IABP) insertion, myocardial infarction, renal failure, wound infection, sepsis or return to the operating room. Intermediate adverse outcomes were defined as hospital readmission for any cardiac disease or late mortality. Logistic regression and Cox proportional hazard models were used to adjust for differences in age, acuity, and medical co-morbidities. Outcomes were compared between teaching and non-teaching cases.

Results
6929 cases were included, 895 of which were identified as teaching-cases. Teaching-cases were more likely to have an EF<40%, pre-operative IABP, CHF, combined CABG/AVRs or total arterial grafting cases (all p<0.01). However, a case being a teaching-case was not a predictor of in-hospital mortality (OR=1.02, 95%CI 0.67–1.55) or the composite short-term outcome (OR=0.97, 95%CI 0.75–1.24). The Kaplan-Meier event-free survival of staff and teaching-cases was equivalent at 1, 3, and 5 years: 80% vs. 78%, 67% vs. 66%, and 58% vs. 55% (log-rank p=0.06). Cox proportional hazards regression modeling did not demonstrate teaching-case to be a predictor of late death or re-hospitalization (HR=1.05, 95%CI 0.94 –1.18).

Conclusions
Teaching-cases were more likely to have greater acuity and complexity than non-teaching cases. Despite this, teaching cases did no worse than staff cases in the short or intermediate term. Allowing residents to perform cardiac surgery does not appear to adversely affect patient outcomes.
Abstract 3253: Dermal Filler Injection: A Novel Approach for Limiting Early Infarct Expansion
Authors: Ryan Liam , Matsuzaki Kanji , Noma Mio , Plappert Theodore J , St. John-Sutton Martin G , Gorman Joseph H , Gorman Robert C
Published: July 2021

Objectives
Early infarct expansion promotes adverse remodeling and is associated with poor long-term prognosis. We hypothesized that thickening the infarcted territory of the LV wall by means of intramyocardial injection of a clinically available acellular hydroxyapatite-based dermal filler would attenuate infarct expansion and improve long-term remodeling after myocardial infarction.

Methods
Twenty-five adult male sheep underwent coronary ligations that create an anteroapical MI. Fifteen animals subsequently underwent injection of 1.3 mL of a viscous hydroxyapatite based preparation into the infarcted territory - 10 served as controls. Rt-3DE was performed at baseline, 30 minutes post-MI, 30 minutes post-injection and then at 2, 4 and 8 weeks post-MI. LV volumes and EF were calculated in each case. Cardiac output was measured at 8 weeks with no inotropic stimulation and then during infusions of 2.5 and 5.0 mcg/kg/min of dobutamine after which all animals were sacrificed. Finally, LV wall thickness was measured within the basal and apical regions of the infarct zone, the borderzone (1 cm strip adjacent to the infarct) and the remote myocardium (base).

Results
All data are presented in the figure

. LV remodeling was attenuated in the treatment animals compared with the control group. Treatment animals had thicker infarcts, higher baseline cardiac output and better response to inotropic stimulation than the control group.

Conclusions
Early post-infarction intramyocardial thickening with an acellular hydroxyapatite gel attenuates LV remodeling and improves contractile function 8 weeks after an anteroapical MI in a clinically relevant large animal model.
Abstract 3302: Contribution of Cardiac F-18 FDG PET Imaging to the Management of Patients with Cardiac Sarcoidosis
Authors: Ishida Yoshio , Fukushima Kazuhito , Kiso Keisuke , Hashimura Kazuhiko , Kamakura Shiro , Nakatani Satoshi
Published: July 2021

Early detection and correct assessment of disease activity are critical for the optimal management of patients with cardiac sarcoidosis (CSRD). There are some recent reports showing F-18 FDG (FDG) uptake by sarcoid granulomas. In the present study, we estimated the significance of cardiac FDG PET imaging in 47 patients (57+/−11 years, 16 males and 31 females) with proven diagnosis of CSRD and receiving steroid therapy (30 – 60 mg prednisolone on alternate days) based on clinical signs of acute myocardial involvement. We interpreted regionally enhanced myocardial FDG uptake as positive in the 5-hr fasting FDG PET imaging. In addition, we determined standardized uptake value (SUV) of the FDG uptake. Before steroid therapy, positive myocardial finding was 89% (42/47) in FDG PET, 55% (21/38) in Tc-99m pyrophosphate tomographic imaging, 68% (30/44) in Ga-67 tomographic imaging, 49% (23/47) in echocardiographically estimated septal wall thinning and 35% (13/37) in biopsy. SUV was above 2.5 in all with positive FDG finding. In 3 patients with severe heart failure and with positive finding in biopsy, myocardial FDG uptake showed diffuse patterns and was hardly interpreted positive. The follow-up studies after steroid therapy revealed that the enhanced FDG uptake gradually reduced and disappeared in 6 months in most of the patients, while positive Ga-67 uptake disappeared soon after therapy. Afterwards, recurrence of active inflammation was symptomatically suspected in 4 patients. Performing FDG PET imaging, they all showed re-enhancement of myocardial FDG uptake, which contributed to decision-making of increasing steroid dose. These results suggest that the FDG PET imaging is a sensitive means in detecting disease activity of CSRD and contributes to the decision-making and evaluation of steroid therapy.
Abstract 3321: Gender Impacts Capillary Density and Skeletal Muscle Composition in Patients With Peripheral Arterial Disease
Authors: Jones William S , Duscha Brian D , Robbins Jennifer L , Aldrich Amy J , Regensteiner Judy G , Hiatt William R , Annex Brian H
Published: July 2021

Background
: Peripheral arterial disease (PAD) is a disorder characterized by impaired blood flow to the legs and maladaptive changes in the skeletal muscle. It is generally accepted that the skeletal muscle characteristics in patients with PAD include decreased capillary density and an altered percentage of oxidative myofibers. The scientific literature is conflicting, and it is based on studies with small sample size and older methodologies of skeletal muscle analysis. In addition, women are under-represented or not included at all in these studies.

Hypothesis
: We hypothesized that there would be differences in skeletal muscle composition in PAD patients compared to healthy controls. We further hypothesized that there would be gender differences in skeletal muscle composition in PAD patients versus healthy controls.

Methods
: Thirty -one patients with PAD and 31 age-, gender-, and activity-matched healthy controls underwent gastrocnemius muscle biopsy. Capillary density analysis and muscle fiber type determination were performed using immunohistochemistry techniques. Capillary density was measured as endothelial cells per muscle fiber and endothelial cells per area (mm
2
).

Results
: There was no significant difference in capillary density in patients with PAD versus healthy controls when measured as endothelial cells per fiber (mean = 1.45 ± 0.43 vs. 1.50 ± 0.35, NS) or area (mean = 1.20 ± 0.29 vs. 1.29 ± 0.33, NS). There was also no difference in muscle fiber type composition between the groups. In the PAD cohort, capillary density was significantly lower in the men versus the women (mean = 1.36 ± 0.35 vs. 1.59 ± 0.51, p=0.005). In our cohort of women, there was no difference in capillary density in patients with PAD versus healthy controls (N=12). In men, capillary density was significantly lower in the PAD group versus healthy controls (N=19, mean = 1.09 ± 0.20 vs. 1.28 ± 0.34, p=0.043).

Conclusions
: Our data fail to confirm the belief that patients with PAD have a decreased capillary density and an altered percentage of oxidative myofibers. However, we did find that gender has an important impact on these characteristics. Further study of skeletal muscle composition in PAD may help to better understand the functional relevance of the gender differences.
Abstract 3342: Adequacy of Inclusion of Post-Procedural Bleeding in a Composite End Point for Assessment of Outcome After Percutaneous Coronary Intervention.
Authors: Schulz Stefanie , Ndrepepa Gjin , Mehilli Julinda , Iijima Raisuke , Bruskina Olga , Berger Peter B , Schömig Albert , Kastrati Adnan
Published: July 2021

Objective: To assess the adequacy of inclusion of post-procedural bleeding in a quadruple composite end point for the prediction of mortality after percutaneous coronary intervention (PCI).

Methods: This study included 5384 patients from 4 ISAR randomized trials on the value of abciximab: ISAR-REACT, ISAR-SWEET, ISAR-SMART 2 and ISAR-REACT 2. Common inclusion criteria were the presence of native coronary artery disease requiring PCI and pretreatment with 600 mg of clopidogrel at least 2 hours prior to the intervention. Patients were randomized to receive either the standard dose of abciximab plus unfractionated heparin or placebo plus unfractionated heparin. Bleeding was defined according to the Thrombolysis in Myocardial Infarction (TIMI) criteria. Primary end point was one-year mortality.

Results: Within the first 30 days there were 314 myocardial infarctions (5.8%), 52 urgent revascularizations (1.0%) and 215 TIMI major or minor bleeding (4.0%). One-year mortality was 3.6% (n=197). Table

shows one-year mortality among patients with or without 30-day adverse events (myocardial infarction, urgent revascularization or bleeding). Cox proportional hazard model that included all of the 3 adverse events along with baseline characteristics of the patients showed that 30-day myocardial infarction, urgent revascularization or bleeding were all independently associated with one-year mortality with adjusted hazard ratios displayed in the table

. The prognostic value of bleeding was not dependent on its classification as major or minor.

Conclusion: Our study supports the inclusion of post-procedural bleeding in a quadruple end point along with death, myocardial infarction and urgent revascularization to assess outcome after percutaneous coronary intervention.

Table.
Abstract 3357: Haemodialysis Induced Contractile Dysfunction is Associated with Acute and Reversible Reduction in Global and Segmental Myocardial Blood Flow
Authors: Burton James , Selby Nicholas , Leccisotti Lucia , Korsheed Shvan , McIntyre Christopher , Camici Paolo
Published: July 2021

Hemodialysis (HD) is associated with acute cardiac ischemia, as evidenced by the development of regional wall motion abnormalities (RWMAs). Repetitive acute myocardial ischemia may lead to the development of chronic left ventricular (LV) dysfunction. This study utilised serial H
2
15
O PET scans to confirm that the development of HD-induced RWMAs was associated with reduction in myocardial blood flow (MBF). Four prevalent HD patients without angiographically significant coronary artery disease (CAD) had measurements of MBF during standard HD and biofeedback dialysis (BFD). All patients underwent serial measurements of MBF using PET. Echocardiography was used concurrently to assess LV function. Hemodynamic variables were measured using continuous pulse wave analysis. Mean pre-HD MBF was within the normal range. Global MBF was acutely reduced during HD (see figure

) (P<0.002). Segmental MBF was significantly reduced in areas that developed RWMAs compared to those that did not (P<0.001). Not all regions with reduced MBF were functionally affected but a reduction in MBF of >30% from baseline was associated with the development of RWMAs (P<0.01). No significant differences in haemodynamic tolerability, RWMA development or MBF between dialysis modality were observed. HD is associated with repetitive myocardial ischemia which in absence of significant CAD may be due to coronary microvascular dysfunction. Stress induced, segmental LV dysfunction correlates with a matched reduction in MBF. Functional post-stress recovery is consistent with myocardial stunning induced by HD. This process may be an important component in the development of heart failure in chronic HD patients.
Abstract 3358: Resistance to Endogenous Erythropoietin Predicts Survival in Anemic Heart Failure Patients
Authors: Van Der Meer Peter , Lok Dirk J , Lipsic Erik , Van Wijngaarden Jan , Brugginnk Pieta W , Voors Adriaan A , Van Gilst Wiek H , Van Veldhuisen Dirk J
Published: July 2021

Background
In response to hypoxia the kidney produces erythropoietin (EPO). Elevated levels of EPO are observed in patients with chronic heart failure (CHF) and are related to an impaired outcome. However it is unknown whether these EPO-levels are adequate for the degree of anemia and how the adequacy of EPO levels relates to prognosis.

Methods
Therefore, we studied 240 CHF patients (96% were in NYHA functional class III). The adequacy of EPO levels was assessed by an observed-predicted ratio. A value <0.9 indicates inadequate low EPO levels (=blunted EPO-response), whereas >1.1 indicates inappropriate high EPO levels (=EPO resistance). Group comparisons were therefore made between

low EPO responders n = 30

normal EPO responders n = 25

EPO-resistance n = 22. Anemia was defined according to the WHO definition (males and postmenopausal females Hemoglobin (Hb) < 3.0 g/dL and premenopausal females Hb < 12.0 g/dL). The primary endpoint was mortality.

Results
During a median follow up of 3.8 years, 98 patients died (41.4% mortality rate). EPO levels were an independent predictor of mortality, also adjusted for hemoglobin levels (HR 1.013, 95%CI [1.007–1.018], p=0.001). Anemia was present in 77 (32%) patients. Inadequate low EPO levels were observed in 30 anemic patients (39%) and related to renal failure (glomerular filtration rate < 30 ml/min/1.73m2 (p<0.009). EPO resistance was present in 22 anemic patients (29%) and was associated with a significant higher mortality rate compared to patients with a normal EPO response and a low EPO response, 72.7% vs 34.8% and 40.0% respectively (p=0.012 and p=0.021, respectively). EPO resistance was an independent predictor of an increased mortality risk in Cox regression analyses adjusted for variables with p<0.10 in the univariate analysis including age, sex and high sensitive CRP; HR 2.63 95%CI [1.12– 6.17], p=0.026, whereas a low EPO response was not associated with an impaired outcome; HR 1.12 95% CI [0.45–2.79], p=0.81, compared to normal EPO responders.

Conclusion
EPO resistance is common in CHF patients and is associated with a high mortality.
Abstract 3379: Feasibility Of Adrenomedullin Infusion In Patients With Acute Myocardial Infarction -a Possible Cardioprotective Therapy Against Ischemic Injury-
Authors: Yasuda Satoshi , Miyazaki Shunichi , Nagaya Noritoshi , Kataoka Yu , Noguchi Teruo , Morii Isao , Kawamura Atsushi , Kangawa Kenji , Miyatake Kunio
Published: July 2021

Background
: Adrenomedullin (ADM) is a 52-amino-acid vasodilator peptide that was originally isolated from human pheochromocytoma. In the previous experimental study with rat ischemia/reperfusion model, ADM reduced infarct size and inhibited myocyte apoptosis. ADM also suppressed the production of oxygen-free-radicals. The present study was designed to evaluate the feasibility of intravenous administration of ADM in patients with acute myocardial infarction (AMI).

Methods
: We studied 10 patients with first AMI (M/F;9/1, mean age;65 years, peak CPK level; 4090 U/L[median]), who were hospitalized within 12 hours of symptom onset. ADM infusion preceded percutaneous coronary intervention (PCI) and was continued at concentration of 0.0125 − 0.025μg/kg/minute for 12 hours. We also studied 10 control AMI patients matched for age, sex and infarct size, who did not receive ADM.

Results
: During ADM infusion, hemodynamics kept stable except one patient with right ventricular infarction. Urinary levels of 8-iso-prostaglandine F2α, which was measured after the reperfusion therapy with ADM infusion as a marker of oxidative stress, was significantly lower in patients who received ADM than those who did not (76 ± 40 vs 174±21 pmol/mol of creatinine, P<0.01). Infarct area (IA) evaluated by magnetic resonance imaging and brain natriuretic peptide (BNP) levels were also different between the two groups (Table

).

Conclusions
: Intravenous administration of ADM, which possesses a variety of cardiovascular protective actions, is feasible and can be adjunctive to PCI. Suppression of oxidative stress generation may be beneficial for attenuation of left ventricular dysfunction and remodeling following AMI.
Abstract 3419: Positive Effect of Bone Marrow Progenitor Cell Transfer on Regional Post Infarction Ventricular Remodeling by Magnetic Resonance Imaging. Insights from the REPAIR AMI Trial.
Authors: Rolf Andreas , Mollmann Susanne , Rixe Johannes , Conradi Guido , Schachinger Volker , Dimmeler Stefanie , Zeiher Andreas , Hamm Christian , Dill Thorsten
Published: July 2021

Objective
: The acute loss of myocytes during infarction increases loading conditions, which in turn triggers adverse remodeling of infarcted, adjacent and remote regions. Late Gadolinium Enhancement (LGE) cardiac MRI (CMR) can distinguish these regions and thus determine the effect of bone marrow progenitor cell (BMC) therapy on regional remodeling and function.

Methods
: 47 patients from the REPAIR AMI trial who underwent CMR at baseline and 12 month were evaluated in a segment by segment fashion according to the AHAs 17 segment model, defining LGE positive segments as infarcted and LGE negative segments as adjacent or remote. We measured enddiastolic wall diameters (WD) and wall thickening (WT) at 0 and 12 month by serial MRI.

Results
: WD decreased in all patients and all segments with a tendency to smaller diameters in BMC treated patients. In the prespecified subgroup of patients with larger infarcts (EF below the median of 48.9%) we observed a positive effect on adverse remodeling in BMC patients not only in infarcted but also in the remote areas. Infarcted segments showed a decrease in WD of 21.9% ± 4.0 SE in the BMC group vs. 8.5% ± 3.4 in the Placebo Group p=0.02. In BMC patients WD decreased in remote segments by 8.1% ± 4.4 SE compared to 4.9% ± 3.3 SE in the Placebo group, p=0.03. This effect on remodeling translates into a functional benefit. In remote segments WT decreases in both gropus but significantly so only in Placebo patients (BMC-7.8% ± 5.4 p= 0.2 vs. Placebo −13.9% ± 4.4 p=0.002, p for interaction 0.4). The largest effect was observed in the infarcted segments where BMC therapy led to an increase in WT of 26.6% ± 5.1 SE compared to Placebo 0.7% ± 4.6 SE p= 0.0001. The positive effect is mediated by wall diameters, regression analysis shows a significant inverse relationship between WD and WT, p = 0.0001

Conclusion
: BMC therapy effectively prevents adverse remodeling not only in the infarct zone but also in remote segments for patients with large infarcts resulting in increased contractility. This seems to be mediated by a positive effect on enddiastolic wall geometry yielding smaller wall diameters.
Abstract 3422: Absolute Myocardial Blood Flow Imaging At 3 Tesla: Comparison With 1.5 Tesla
Authors: Christian Timothy , Bell Stephen P , Frankish Mei Lee L , Whitesell Lawrence
Published: July 2021

First-pass (FP) MR myocardial perfusion (perf) imaging can quantify absolute myocardial blood flow (MBF) but images are of low signal at conventional field strength. Purpose: To determine the accuracy of absolute FP MBF measures at 3 Tesla and compare these measures with FP 1.5T using MBF by microspheres (mcsp) as the gold-standard.

Methods: A pig model was used to alter MBF in a coronary artery during FP MRI (intracoronary adenosine followed by ischemia). This produces an active zone with a range of MBF and a control zone. Mcsp were injected into the left atrium with concurrent reference sampling. FP MR perf imaging was performed at 1.5T (n=8) or 3.0T (n=7) using a saturation-recovery gradient echo sequence in short-axis slices (SAX) during a bolus injection of 0.025mmol/kg gadolinium-DTPA. Fermi function deconvolution was performed on active and control ROI from SAX slices with an arterial input function from the LV cavity. These MR values of MBF were matched to mcsp values obtained from SAX slices at pathology.

Results: Occlusion MBF was 0.22±.26 ml/min/g, adenosine MBF was 2.11±1.13 ml/min/g and control zone MBF was 0.70±0.22ml/min/g. The correlation of MR FP MRI with mcsp is shown in Figure 1

: 3T) r=0.95, p<0.0001, 1.5T, r=0.94, P<0.0001. The 95% confidence limits were slightly narrower at 3T (3T=0.41ml/min/g, 1.5T=0.55ml/min/g, p=NS. FP MRI characteristics were better at 3T (noise, SNR, contrast enhancement all superior at 3T). In zones where MBF<0.50ml/min/g, the correlation with mcsp was closer at 3T (r=0.55 at 1.5T, r=0.85 at 3T).

Conclusion: Absolute MBF by FP perfusion imaging is accurate at both 1.5 and 3T. Signal quality is better at 3T which may confer a benefit in low MBF zones.
Abstract 3428: Presence Of Renal Simple Cysts Is Associated With Increased Risk For Abdominal Aortic Aneurysm
Authors: Song Bong Gun , Jang Shin Yi , Park Yong Hwan , Lee Sang Yeub , Choe Yeon Hyeon , Do Young Soo , Kim Dong Ik , Kim Young Wook , Sung Jidong , Kim Duk-Kyung
Published: July 2021

Background : An increased prevalence of abdominal aortic aneurysm (AAA) has been demonstrated in patients with emphysema or inguinal hernia. Therefore, it has been suggested that the cause of AAA is a degenerative disorder of the connective tissue that can not always be explained by means of atherosclerosis. We hypothesized that the presence of renal simple cysts, another possible manifestation of connective tissue weakness, is associated with the increased risk for AAA. We compared incidence of renal simple cyst between the group of patients with AAA and healthy control group.

Methods : We reviewed 279 patients with AAA and 1397 healthy control group who underwent abdominal computed tomography as a routine health screening from 1994 to 2006 in Samsung Medical Center. AAA was defined as an aortic diameter equal to or greater than 40 mm. Comparisons between groups were made for established risk factors for AAA.

Results : AAA group has significantly more diabetes, smoking, history of anti-hyperlipidemic medication, hypertension, metabolic syndrome, higher systolic blood pressure than control group (all
p
values <0.0001). In the univariate analysis, prevalence of renal cysts (
p<
0.0001), bilateral renal involvement of cysts (
p<
0.0001), number of renal cysts (
p<
0.0001), and sum of sizes of renal cysts (
p<
0.0001) were significantly higher in AAA group as compared with control group. In the multivariate analysis, a person with renal cyst was more likely (OR: 4.379, CI: 3.402–5.636) to have AAA after adjustment for age, gender, smoking, hypertension, diabetes, HDL and LDL cholesterol. This relationship was similar for bilateral renal involvement of cysts, number of renal cysts, and sum of sizes of renal cysts. Neither a diameter nor an expansion rate of AAA was associated with the size of renal cysts.

Conclusion: Patients with AAA have increased burden of renal simple cysts compared to healthy control group. The structural weakness predisposing for renal simple cysts may be associated with the initiation of AAA formation. Prospective study is needed to determine whether the presence of renal cysts can be considered as a risk factor of AAA.
Abstract 3444: The Effect of Alpha Lipoic Acid on Porcine Coronary Stent Restenosis
Authors: Jeong Myung Ho , Bae Eun Hui , Lim Sang Yup , Moon Jae Youn , Kim Ju Han , Ahn Young Keun , Hong Young Joon , Cho Jeong Gwan , Kang Jung Chaee
Published: July 2021

Objective: We evaluated the ability of alpha lipoic acid (ALA) to affect on coronary instent restenosis (ISR) in a porcine model.

Methods:

In vitro experiment: We stimulated porcine VSMC using G-CSF in the presence or absence of ALA. Activation of Akt, vascular endothelial growth factor (VEGF), extracellular signal-regulated kinase (ERK) and signal transducer and activator of transcription (STAT)-3 were determined using western blot. And also, cell proliferation and migration assay were determined.

In vivo experiment:Balloon overdilation injuries were performed in 2 coronary arteries in 12 pigs. Four weeks after the balloon overdilation injury, 24 bare metal stents were placed for 24 injured coronary arteries. We randomized into two groups (12 stents per group; control group: aspirin and clopidogrel only, ALA group: aspirin and clopidogrel plus 100 mg/kg ALA during 4 weeks).

16 bare metal stents were implanted randomized two coronary arteries in 8 pigs. Group I was control stent group (n=8), Group II was ALA coated stent group (n=8). Follow-up coronary angiogram (CAG) and histopathologic assessment were performed at 4 weeks after stenting.

Results:

G-CSF increased the phosphorylation of ERK and STAT-3, but after pretreatment of ALA, the phosphorylation of ERK and STAT-3 were significantly reduced.

On histopathologic analysis, injury score, internal elastic lamina(IEL) area did not differ significantly between the two groups. The neointimal area was 7.3±0.9 mm2 in control group and 2.2±1.1 mm2 in ALA group (p<0.001), and the histopathologic area of stenosis(AS) was 75.9±8.5 % in control group, 23.5±10.5 % in ALA group (p<0.001).

The injury score and IEL area were not significantly different between the two groups.

The neointimal area was 7.4±1.1 mm2 in control group and 1.4±0.8 mm2 in ALA group (p<0.001), and the AS was 77.6±10.9 % in control group, 15.6±7.6 % in ALA group (p<0.001). The number of inflammatory cells within neointima was lower in ALA group (63.2±23.7 % vs. 17.6±11.6 %, p<0.001).

Conclusion: ALA inhibits the activation of ERK, STAT-3 and proliferation of VSMC. Both high dose of oral ALA and ALA coated stents inhibit neointimal hyperplasia in a porcine ISR model
Abstract 3454: Fine Mapping Of A Chromosome 16 Locus Associated With Low High-density Lipoprotein Cholesterol Level (HDL-C) In French Canadian Subjects
Authors: Dastani Zari , Marcil Michel , Lee Jenny C , Pajukanta Paivi , Gaudet Daniel , Genest Jacques , Engert James C
Published: July 2021

Low HDL-C is a known independent risk factor for coronary heart disease. Levels of HDL-C are influenced by both genetic and environmental factors. We previously performed a quantitative linkage analysis in two independent studies of the French Canadian founder population: a Quebec-wide study (QUE) consisted of 362 individuals from multigenerational families, and 410 individuals from families of the Saguanay-Lac St-Jean region (SLSJ). The results demonstrated a linkage to the locus 16q23–24 in both studies. This locus has been implicated in previous linkage scans for HDL-C in multiple studies from different populations. All of them resulted in linkage peaks that are less than 12 cM far from our peak, suggesting the existence of one or more genes in this specific locus. We examined the region by SNP fine mapping and used family based association and case-control association analysis. Using families from the QUE study, defining HDL-C <5th percentile (age/gender-matched) as cases, the region was narrowed from 25 cM to 18.1 cM. Affected members from four families share a 2 microsatellite haplotype. SNPs genotyped in this locus allowed us to narrow down the shared haplotype to 4Mb. A case-control association study in the SLSJ study sample (cases <5 percentile HDL-C, controls >40 percentile HDL-C) identified several significant SNPs, one of which was located in the same region as the shared haplotype from the QUE families. Constructing a haplotype of this SNP and a nearby SNP, increased the evidence for association (p =0.016 to 0.0097). The CHST6 gene, located within this region, has been previously identified in macular corneal dystrophy. Because of the presence of occular manifestations with other genes associated with low HDL-C (e.g. LCAT, ApoA1), we sequenced the CHST6 gene and also its homologue CHST5, which is located in the same region. We found three non-synonymous variants in these two genes. One of the variants in the CHST6 gene showed a strong segregation in the four families sharing the microsatellite haplotype. This same variant also demonstrated an odds ratio >2 in the case/control sample, but this was not significant due to the small sample size. Our data present strong evidence for a HDL-C gene on chromosome 16q23–24 that may be related to the CHST6 or CHST5 loci.
Abstract 3457: Methylenetetrahydrofolate Reductase Gene Polymorphism C677T And The Risk Of Premature Myocardial Infarction With “Normal” Coronary Arteries.
Authors: Rallidis Loukianos , Komborozos Christoforos , Gialeraki Argyri , Zolindaki Maria , Vavoulis Panagiotis , Papadopoulos Kostas , Travlou Anthi , Kremastinos Dimitrios
Published: July 2021

Purpose: the pathogenetic mechanism of acute myocardial infarction (AMI) in young patients remains unknown. We explored the impact of homocysteine and its main genetic modulator

Table 2

methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism in patients who sustained AMI under the age of 36 years.

Methods: we recruited 136 consecutive patients who had survived their first AMI before the age of 36 years (mean age=32 ± 3.1 years, range 23–35 years, 121 men). Blood was taken for lipids and homocysteine levels within 12 hours from admission. The MTHFR C677T polymorphism was also determined with polymerase chain reaction. All patients underwent cardiac catheterization. One hundred-three healthy individuals without a family history of coronary heart disease (CHD), matched for age and sex served as controls.

Results: coronary angiogram revealed significant CHD in 104 patients while 32 (23.5%) had no significant CHD. The prevalence of homozygotes for C677T polymorphism [T/T genotype] was 27.2% in patients and 14.6% in controls (p=0.02). In the subgroup of patients who had AMI and “normal” coronary arteries the frequency of homozygotes was 43.8% (p=0.001 versus controls and p=0.02 versus patients with significant CHD). The table presents lipids and homocysteine levels in AMI patients with “normal” coronary arteries and controls. Logistic regression model showed that the odds ratio for a young individual with T/T genotype to develop AMI with “normal” coronary arteries was 5.2 (confidence interval 1.2–23, p=0.03) adjusted for smoking habits, body mass index, hypertension and diabetes mellitus.

Conclusions: the presence of homozygocity for MTHFR C677T polymorphism is associated with 5-fold higher risk for premature AMI with “normal” coronary arteries. This suggests that homocysteine may be involved in the formation of an obstructive thrombus in coronary arteries, especially in young individuals without significant underlying atheromatic burden.
Abstract 3488: Hyperuricemia and the Risk of Isolated Hypertension among Young People without Cardiovascular and Metabolic Risk Factors: The CARDIA Study
Authors: Krishnan Eswar , Choi Hyon K , Kuller Lewis H , Liu Kiang
Published: July 2021

PURPOSE: The association between higher serum uric acid (SUA) levels and hypertension in the context of the metabolic syndrome is well known. If such an association was causal, one would expect to demonstrate a link between hyperuricemia and incidence of isolated hypertension - a hypothesis that has not been tested so far.

METHODS: We used the 15-year limited-access data from the prospective cohort study of Coronary Artery Risk Development in young adults (CARDIA), sponsored by the National Institutes of Health, to identify a group of non-smoking young people with normal blood pressure and free of insulin resistance, hyperlipidemia, obesity, and a family history of cardiovascular diseases. These young people aged between 18 and 30 years at baseline were followed-up for a period of 15 years by 6 study visits where all cardiovascular risk factors were reassessed. Incidence of JNC-7 hypertension was the outcome of interest in Cox proportional hazards models where age, gender, race, lipid levels, blood pressure, alcohol, body mass index, smoking and serum insulin levels (time-varying where appropriate) were the covariates. Baseline serum uric acid (continuous) was the independent variable of interest. A second set of Cox regression analyses was performed among the subgroup of these individuals who remained free of all cardiovascular risk factors (except for hypertension) over the 15-year follow up.

RESULTS: Out of the 5113 CARDIA participants at baseline, 2057 subjects were free of cardiovascular risk factors at baseline and were available for evaluation at year 15. Over the follow-up period, 828 subjects developed hypertension. In multivariate Cox models, each mg/dl increase in serum uric acid was associated with a hazard ratio of 1.45 (1.09–1.91). In the second set of analyses, 753 were free of all cardiovascular risk factors at baseline and remained free of any of the components of the metabolic syndrome except hypertension (n = 122 incident cases of hypertension) were studied. In these analyses each mg/dl increasse in SUA was associated with a risk adjusted hazard ratio of 1.60 (95% CI 1.02–2.49).

CONCLUSIONS: Unrelated to the other features of the metabolic syndrome, higher levels of SUA among young people predicts isolated hypertension.