MAGYAR KARDIOLÓGUSOK TÁRSASÁGA

[2012][135] Comparison of mitral annular shape and function in different forms of myxomatous valve disease using real-time three-dimensional transesophageal echocardiography

Authors:
A. Apor, B. Sax, T. Huttl, A. Nagy, A. Kovacs, B. Merkely., Semmelweis University, Department of Cardiac Surgery, Budapest, Hungary

Session:
3D echo in valvular heart disease

Citation:
European Heart Journal 2012;Vol.32(Abstract Supplement):17

Purpose: The dynamic change of mitral annular geometry during the cardiac cycle is a determinant of optimal leaflet coaptation. Our study aimed to test the hypothesis that the dynamic morphology of the mitral annulus (MA) is significantly altered depending on the etiology of the valve disease, and to certify that in myxomatous valve disease (MVD) the subgroups of Barlow disease (BD) and fibroelastic deficiency (FED) vary essentially in the characteristics of MA.

Methods: We obtained real-time three-dimensional (3D) full volume and 3Dzoom loops during transesophageal echocardiography (Philips iE33) in 89 subjects. Patients with organic (rheumatic, senile calcific) mitral valve disease (OMD, n=25), 45 with myxomatous valve disease (BD, n=16, FED, n=29), and normal control subjects (NC, n=19) were compared. Dataset was analyzed off-line by MVQ, Qlab 7.1 software. Several geometric parameters: 3D minimal surface area (A3D), ellipticity (E), and height (H) of the mitral annulus were measured at 7 specific time points of the cardiac cycle. Contractility of MA was determined by the maximal area change-to-maximal area ratio (DA3D%). After normality testing (Shapiro-Wilk), parametric (t-test, ANOVA, Fisher's post hoc test) tests were used for statistical analysis.

Results: In the MVD group annular area averaged over the cardiac cycle, corrected to body surface area was significantly enlarged compared to OMD and controls (mean±SD: 806±160 vs. 600±217 vs. 517±89 mm2, all p<0.001). The geometry of MA was similar between MVD and controls, significant annular flattening and circular remodeling could be observed in the OMD group (OMD vs. NC: H: 3.54±0.92 vs. 4.42±0.84mm, p<0.01; E: 112.0±7.1 vs. 120.8±10.0%, p<0.01). The average number of prolapsing scallops was 5.25 in BD and 1.9 in FED. In each group the minimum value of A3D occurred in protosystole, while maximal value in meso-telesystole. Annular contraction measured by DA3D% was hypodynamic in OMD and FED, and hyperdynamic in BD (BD vs. OMD and FED: 23.9±12.0 vs. 17.0±8.0 and 17.0±7.5, p<0.05 for both; NC: 20.5±6.5). In the OMD, FED and control groups cyclic annular area change showed similar characteristics in time, but the BD group displayed a unique biphasic contraction pattern with enhanced elasticity.

Conclusion: In spite of similar excessive leaflet motion in the various forms of myxomatous mitral valve disease, dynamic annular geometry alters significantly. Barlow disease and fibroelastic deficiency represent different entities regarding the remodeling and dynamic behavior of the annulus, which should influence surgical repair techniques.

[2012][239] The soluble guanylate cyclase activator cinaciguat improves cardiac dysfunction in diabetes mellitus

Authors:
T. Radovits, A. Olah, B. Nemeth, L. Hidi, E. Birtalan, G. Kokeny, G. Szabo, B. Merkely.,Semmelweis University, Heart Center, Budapest, Hungary; Semmelweis University, Department of Pathophysiology, Budapest, Hungary, University Hospital of Heidelberg, Department of Cardiac Surgery, Heidelberg, Germany

Session:
Young Investigators Awards Session:\ Clinical Science

Citation:
European Heart Journal 2012;Vol.32(Abstract Supplement):178

Purpose: Patients with diabetes mellitus exhibit cardiovascular dysfunction along with increased oxidative stress and decreased nitric oxide – cyclic guanosine monophosphate (cGMP) signalling. It has been reported, that elevated intracellular cGMP-levels contribute to an effective cytoprotection against oxidative stress. In this study we investigated the effects of cinaciguat, a newly developed soluble guanylate cyclase activator on myocardial dysfunction in type-1 diabetic rats.

Methods: In male Sprague-Dawley rats diabetes was induced by a single ip. injection of streptozotocin (60mg/kg). In the treatment groups, cinaciguat (10mg/kg/d) was applied orally for 8 weeks. Rats of the control groups received vehicle for the same time. After the treatment left ventricular (LV) pressure-volume relations were measured by using a microtip Millar pressure-volume conductance catheter, and indexes of contractility (e.g. preload recruitable stroke work (PRSW)) were calculated. Blood plasma and myocardial tissue samples were collected for determination of cGMP-levels and immunohistochemical analysis, respectively. Myocardial gene expression analysis has been performed by quantitative real-time polymerase chain reaction (qRT-PCR).

Results: When compared to the non-diabetic controls, diabetic rats showed impaired left ventricular contractility (PRSW: 49.5±3.3 vs. 83.0±5.5mmHg; p<0.05) and a marked diastolic dysfunction (time constant of LV pressure decay, Tau: 17.3±0.8 vs. 10.3±0.3ms), which was significantly improved by cinaciguat (PRSW: 66.8±3.6mmHg, Tau: 14.9±0.6ms in the diabetes+cinaciguat group). The treatment had no hemodynamic effects in non-diabetic control animals. Diabetes was associated with increased myocardial immunoreactivity for transforming growth factor beta (TGF-b) along with enhanced gene expression for atrial natriuretic peptide (ANP), heat shock protein 70 (Hsp70) and matrix metalloproteinase-9 (MMP-9), which were all reversed after cinaciguat treatment. Efficacy of the therapy was reflected by markedly elevated levels of cGMP in the diabetes+cinaciguat group compared to control (44.2±11.4 vs. 16.1±2.0pmol/ml plasma).

Conclusion: Our results demonstrate that cinaciguat prevents diabetes-associated deleterious myocardial changes and improves diabetic cardiac dysfunction in our rat model. Pharmacological soluble guanylate cyclase activation might represent a novel therapy approach for diabetic cardiomyopathy.

[2012][1054] Changes in renal function in real-life chronic heart failure patients on optimized therapy

Authors:
B. Szabo, D. Vagany, M. Dekany, B. Muk, B. Ancsin, R.G. Kiss, N. Nyolczas.,State Health Centre, Budapest, Hungary

Session:
3D echo in valvular heart disease

Citation:
European Heart Journal 2012;Vol.32(Abstract Supplement):17

Background: Many randomized controlled chronic heart failure trials showed that renal function remains stable on long term if patients are strictly controlled. However patients included in these trials are pre-selected by compliance and risk for complications. Therefore less is known about changes of renal function in a real-life population.

Aim: To investigate the long-term changes of glomerular filtration rate (GFR) in a patient cohort followed at a heart failure clinic.

Patients and method: 552 consecutive patients followed at our heart failure outpatient clinic were included (age: 62.8±13.5 years, male: 75.2%, ischemic etiology: 52.7%, diabetes: 37.9%, left ventricular ejection fraction (LVEF): 30.7±9.1%, baseline GFR: 66.6±24.0ml/min, systolic blood pressure: 126.6±23.6mmHg). After inclusion therapy has been optimized and device therapy (CRT: 17.9%, ICD: 15.8%) applied for all patients according to current guidelines. Patients were divided into 3 groups according to baseline GFR (<30ml/min: 28 pts, 30-60ml/min: 192 pts,>60ml/min: 332 pts). Changes in GFR were assessed at 6 and 12 months and every 12 months thereafter for up to 5 years.

Results: In the whole cohort GFR decreased in the first 6 months significantly (p<0.05) by -7.6±18.6ml/min and showed no further significant change in the following years. The same changes could be observed in patients with ischemic etiology (-7.5±17.7ml/min), in those over 65 years (-7.8±16.7ml/min), in patients with an LVEF<30% (-6.3±18.7ml/min), and in diabetics (-5.6±15.9ml/min), all p<0.05. In patients with severe renal dysfunction (baseline GFR<30ml/min) renal function improved by optimizing therapy (+5.5±9.1ml/min), while in those with moderate renal dysfunction (baseline GFR 30-60 ml/min) GFR showed a small but significant early deterioration (-1.1±14.9ml/min), and those with a GFR>60ml/min GFR decreased on treatment optimization (-13.3±19.5ml/min) and remained stable after that.

Conclusion: In a real-life chronic heart failure population renal function worsens in the early period of treatment optimization, however it remains stable on long term thereafter. In patients with severe renal dysfunction therapeutic changes may significantly improve renal function.

[2012][P4445] Effective radiation dose to obtain coronary morphology and function: comparison of a non-invasive and an invasive strategy

Authors:
G. Toth, A. Ntalianis, M. De Booj, S. Pyxaras, L. Di Serafino, F. De Vroey, P. Vanhoenacker, P. De Bondt, W. Wijns, B. De Bruyne. 1OLV Hospital Aalst, Cardiovascular Center, Aalst, Belgium

Session:
Poster session 5

Citation:
European Heart Journal 2012;Vol.32(Abstract Supplement):778

Background: Diagnosis and treatment guidance of patients with suspected coronary artery disease (CAD) should rely on combined anatomic and functional data. Yet, there is growing awareness about the detrimental effect of radiation associated with diagnostic procedures.

Aim: To compare the Effective Radiation Dose (ERD) needed to obtain coronary anatomy and function by a non-invasive and an invasive diagnostic strategy.

Methods: Detailed ERD measurements were obtained during two different periods (2009, n=479; and 2010, n=207, after both the coronary computed tomography angiography and the catheter laboratory had been renewed). The non-invasive strategy consisted in the combination of the Coronary Computed Tomography Angiography (CCTA) and 99mTc-MIBI SPECT (MPI). The invasive strategy included Coronary Angiography (CA) and Fractional Flow Reserve (FFR) measurement of every angiographycally intermediate lesion (30-70% diameter stenosis by visual estimate).

Results: For the period of 2009 total ERD of the combination of CCTA and MPI (35.25±7.71 mSv) was significantly larger than the total ERD of the combination of CA and FFR (16.67±10.45 mSv; p less than 0.0001). For 2010-2011 the total ERD was 22.81±8.78 mSv in average for CCTA combined with MPI (n=143), and 10.36±5.87 mSv for CA and FFR (n=64) (p less than 0.0001; Figure).

Figure 1. ERD of different modalities in 2010.


Conclusion: The use of up-to-date equipments and algorithms is associated with a marked reduction in ERD for both non-invasive and invasive strategies between the two periods. Yet, the combination of CA and FFR is still associated with a significantly lower ERD in both periods. This should be accounted for when planning diagnostic work-up in patients with suspected CAD.

[2012][P3258] Frequent implantable cardioverter-defibrillator lead complication during orthotopic heart transplatation

Authors:
P. Abraham, K. Caliskan, A. Kardos, D. Theuns, A. Maat, A. Balk, L. Jordaens, T. Szili-Torok. Hungarian Institute of Cardiology, Budapest, Hungary; Erasmus Medical Center, Thoraxcenter, Department of Cardiology, Rotterdam, Netherlands; Erasmus Medical Center, Department of Cardio-Thoracic Surgery, Rotterdam, Netherlands

Session:
Poster session 4

Citation:
European Heart Journal 2012;Vol.32(Abstract Supplement):540

Purpose: The purpose of this retrospective, single-centre study was to evaluate complications with previously implanted implantable cardioverter-defibrillator (ICD) leads in patients who underwent heart transplantation (HTX). A high proportion of patients on the waiting list for HTX have an ICD system. Surgical removal of the whole ICD system is part of the orthotopic HTX procedure and it is usually carried out without complications.

Methods: Medical records of 84 patients with previously implanted ICD systems who underwent HTX in the past 6 years in the Erasmus Medical Center, Rotterdam were reviewed for ICD lead-related adverse events (AE).

Results: No AEs were observed in the single-coil group. The incidence of AEs was 22% in the dual-coil cohort of 51 patients. All AEs were retained fragments of the proximal shock coils of the ICD leads. Fragment retention was independent of age, gender, lead age, the etiology of heart failure, the duration of HTX, or from the heart surgeon in the dual-coil group. The St Jude Medical Riata lead family was overrepresented (7/11) in the AE group owing to its unique shock coil fixation design.

Conclusion: ICD lead fragment retention with a potential risk for further complications is highly prevalent in post-HTX patients who received dual-coil defibrillation leads while on the waiting list. Therefore, more awareness for the technique of dual-coil lead extraction during HTX is warranted. The use of single-coil leads and early removal of remnants should be considered.

[2012][P5474] Stenosis significance by angiography: small versus large vessels

Authors:
G. Toth, M. Hamilos, S. Pyxaras, L. Di Serafino, F. De Vroey, E. Barbato, W. Wijns, B. De Bruyne. 1OLV Hospital Aalst, Cardiovascular Center, Aalst, Belgium

Session:
Poster session 7

Citation:
European Heart Journal 2012;Vol.32(Abstract Supplement):1011

Background: Coronary Angiography is known to correlate modestly with functional lesion severity. However the factors which influence the relationship between percent diameter stenosis and fractional flow reserve (FFR) have not been properly investigated.

Aim: To compare the diagnostic accuracy of Quantitative Coronary Angiography (QCA)-derived percent diameter stenosis (DS) in predicting FFR in coronary arteries of various sizes.

Methods: Between 2001 and 2012, 6281 coronary artery stenoses were assessed by QCA and FFR measurement: reference lumen diameter (RLD) and QCA-derived DS were calculated and FFR was measured in every case.

Results: Stenoses were grouped according to the size of the artery into small vessels (RLD smaller than 2.5 mm), intermediate vessels (RLD between 2.5 and 3.5 mm) and large vessels (RLD bigger than 3.5 mm). Diagnostic value of QCA-derived DS in identifying functionally significant lesions (FFR?0.80) was assessed by calculating the ROC curves for each group (Figure). By comparing the areas under the curves (AUC), the diagnostic accuracy of QCA was found significantly lower in small vessels (AUC=0.70; SE=0.01) than in the large vessels (AUC=0.81; SE=0.01; p less than 0.001).Especially, in angiographically intermediate stenoses (DS between 30-60%), i.e. the clinically relevant range, the discordance between DS and FFR occurs significantly more often in small vessels than in large vessels (42.07% vs 34.68%, respectively; p less than 0.05).

Figure 1. ROC curves QCA-DS related to the RLD.


Conclusion: The accuracy of angio-derived DS in identifying the functional stenosis severity depends on the caliber of the artery: the smaller the artery the larger the inaccuracy.

[2012][P776] Concomitant phosphodiesterase 5-inhibition enhances myocardial protection of inhaled nitric oxide after ischemia-reperfusion injury

Authors:
A. Lux, P. Pokreisz, M. Swinnen, E. Caluwe, H. Gillijns, Z. Szelid, B. Merkely, S. Janssens.,Semmelweis University, Heart Center, Budapest, Hungary; Catholic University of Leuven, Leuven, Belgium

Session:
Poster session 1

Citation:
European Heart Journal 2012;Vol.32(Abstract Supplement):109

Purpose: Enhanced nitric oxide (NO)/cGMP signaling attenuates LV functional deterioration after myocardial infarction (MI). We studied phosphodiesterase-5 (PDE5) expression after ischemia-reperfusion injury (I/R) and tested the effect of inhaled NO (iNO), tadalafil (TAD), a selective PDE5 inhibitor, or the combination (iNO+TAD) on MI size, LV-remodeling and function.

Methods: In C57Bl6J mice, ischemia was induced by 60 min proximal LAD ligation followed by reperfusion. Animals were randomized into non-treated (CON), iNO, TAD and iNO+TAD groups (n=20 per group), circulating and cardiac cGMP-levels were determined at baseline and PDE5 expression levels (real time qPCR) determined at baseline, 3d and 4w after I/R. Plasma troponin I (TnI) was measured using ELISA at 0, 4, 24, and 72 h after I/R. TAD (4 mg/kg) was administered orally 60 min before ischemia and NO inhalation (80 ppm) started 30 min before and continued 20 min during reperfusion. After 3d, MI size was measured using planimetry on TTC-stained LV sections and infiltrating myeloperoxidase–positive (MPO) cells were counted in reperfused territories. After 4w, LV function and remodeling was evaluated using TTE (30 MHz VisualAonics) and pressure-volume (PV) catheterization.

Results: In intact mice, myocardial PDE5 expression was similar in all groups while circulating and cardiac cGMP levels increased significantly in iNO+TAD (n=7 for each, P<0.01 vs CON, P<0.05 vs NO or TAD), with either therapy alone having a modest effect. In contrast, myocardial PDE5 expression at 3d and 4w after I/R was 2-fold increased in CON. After 4h R, peak TnI levels were reduced by 30% in iNO and TAD (P=NS), and by 50% in iNO+TAD (n=10 for each group, P<0.05 vs CON). MI size, relative to area-at-risk, was significantly smaller at 3d in iNO, TAD, and iNO+TAD (35±3, 24±4, 34±4 vs 44±2% in CON, resp. P<0.05). All treatments tend to reduce MPO-cell infiltration to similar extent compared to CON (P=NS, N=6 for each). After 4w, TTE revealed better-preserved fractional shortening and less LV dilatation in all treated groups with greatest benefit for iNO+TAD (43±1 vs 33±2% and 3.3+0.1 vs 4.0±0.2 mm in CON, resp. P<0.001 for both). Similarly, iNO+TAD showed a better contractile function recovery during PV measurements than either treatment alone.

Conclusion: Combined treatment with iNO and selective PDE5 inhibition during acute myocardial ischemia is safe, synergistically protects the myocardium from early ischemic injury, and promotes LV functional recovery over time. Combination therapy may represent a promising strategy to reduce ischemic damage and enhance myocardial repair.

[2012][P925] Impact of logistic network organization in reduction of STEMI mortality in an unselected population from central romania

Authors:
I.S. Benedek, B. Jako, T. Benedek.,University Emergency Hospital, Targu Mures, Romania

Session:
Poster session 1

Citation:
European Heart Journal 2012;Vol.32(Abstract Supplement):146

Aims: To investigate evolution of ST-Elevation Myocardial Infarction (STEMI) treatment and STEMI –related mortality in an unselected population from a region of 1 million people in central Romania in the period of 2004-2011, and to show the role of organizational and educationalwork in increasing rates of primary PCI and reducing STEMI mortality in thisregion

Methods and results: In 2004 a STEMI network for organization of logistics related to STEMI treatment was initiated in a territory of 1 million people, encompassing a primary PCI centre and 13 territorial hospitals without catheterization facilities. Data related to all unselected patients presenting with STEMI in these hospitals were collected and introduced in a Regional Registry of STEMI, the first registry of such kind in Romania. In order to increase the number of patients referred for primary PCI, organizational andeducational activities have been performed by the medical team of the primaryPCI centre with support from the Stent for Life initiative. The total number of STEMI cases enrolled in the registry has been increasing continuously from 440STEMI/year diagnosed in 2004 to 1.299 STEMI cases/year diagnosed in 2011. Only 48.14% from the total population of the registry presented to the hospital inthe first 12 hours after symptoms onset. In 2004, primary PCI rate was 10.88% and thrombolysis rate was 16.06%, representing a total reperfusion rate of 26.94%,while in 2011 a rate of 78.64% primary PCI was achieved, in parallel with a 8.51% thrombolysis rate, representing a 87.15% rate of reperfusion strategy in the global registry. A more correct use of reperfusion therapy has been implemented in the territory already in 2009, when 56.71% of registry population received primaryPCI and 24.57% received thrombolysis, representing an 81.28% reperfusion rate. The global registry mortality showed a significant decrease from 23.18% in 2004 to 13.39% in 2011. For cases presented before 12 h from symptoms onset mortality has been continuously decreasing from 20.73% in 2004 to 6.35% in 2011.

Conclusion: Reduction of STEMI related mortality was possible via implementation ofprimary PCI even in a region from the country with the lowest budget dedicated to healthcare from Europe. It took at least 5 years of intensive work to implement a new therapeutic strategy in the community. A national strategy for primary PCI could have a significant impact especially in those regions where the territory has been prepared with appropriate organizational efforts, including education and logistic measures.

[2012][P961] Correlation of local and regional arterial stiffness parameters in patients with coronary artery disease

Authors:
Z. Lenkey, B. Gaszner, M. Illyes, Z.S. Sarszegi, I. Horvath, F. Molnar, A. Cziraki.,Heart Institute, Faculty of Medicine, University of Pécs, Pécs, Hungary; Budapest University of Technology and Economics (BME), Budapest, Hungary

Session:
Poster session 1

Citation:
European Heart Journal 2012;Vol.32(Abstract Supplement):156

Background: Aortic pulse wave velocity (PWVao) and augmentation index (AIXao) are commonly used to identify the very early stage of atherosclerotic disease. Carotid stiffness may be of particular interest, since in that artery atherosclerosis is frequent particularly in patients with verified coronary artery disease (CAD).

Aim: 180 CAD patients were enrolled in our examination and were compared to 180 age-and gender-matched, apparently healthy control subjects. Aortic augmentation index and pulse wave velocity were measured with the recently invasively validated, oscillometric Arteriograph device. Local arterial stiffness parameters were determined on the common carotid artery by using Doppler echo-tracking system.

Methods: In 2004 a STEMI network for organization of logistics related to STEMI treatment was initiated in a territory of 1 million people, encompassing a primary PCI centre and 13 territorial hospitals without catheterization facilities. Data related to all unselected patients presenting with STEMI in these hospitals were collected and introduced in a Regional Registry of STEMI, the first registry of such kind in Romania. In order to increase the number of patients referred for primary PCI, organizational andeducational activities have been performed by the medical team of the primaryPCI centre with support from the Stent for Life initiative. The total number of STEMI cases enrolled in the registry has been increasing continuously from 440STEMI/year diagnosed in 2004 to 1.299 STEMI cases/year diagnosed in 2011. Only 48.14% from the total population of the registry presented to the hospital inthe first 12 hours after symptoms onset. In 2004, primary PCI rate was 10.88% and thrombolysis rate was 16.06%, representing a total reperfusion rate of 26.94%,while in 2011 a rate of 78.64% primary PCI was achieved, in parallel with a 8.51% thrombolysis rate, representing a 87.15% rate of reperfusion strategy in the global registry. A more correct use of reperfusion therapy has been implemented in the territory already in 2009, when 56.71% of registry population received primaryPCI and 24.57% received thrombolysis, representing an 81.28% reperfusion rate. The global registry mortality showed a significant decrease from 23.18% in 2004 to 13.39% in 2011. For cases presented before 12 h from symptoms onset mortality has been continuously decreasing from 20.73% in 2004 to 6.35% in 2011.

Results: In the CAD group the PWVao and AIXao values increased significantly (10.1±2.4 m/s and 34.2±14.8%) compared to control group (9.5±1.5 m/s and 30±12.7%; p<0.05). We observed similar significant increase in the local stiffness parameters (PWVcar and AIXcar) in CAD group. Furthermore, we found strong correlation for PWV and AIX values which were measured with the Arteriograph and those obtained using echo-tracking method (r=0.57; p<0.001 for PWV, and r=0.65; p<0.001 for AIX values).

Conclusion: Our results suggest that the increased cardiovascular risk could be assessed by the similar extent with the local, and central arterial stiffness parameters in patients with verified CAD.

[2012][P1586] Awareness of peripheral arterial disease helps to reach blood pressure and cholesterol target values: results of the hungarian ankle/brachial index screening program (ERV)

Authors:
K. Farkas, Z. Jarai, E. Kolossvary, A. Ludanyi, I. Kiss.,St. Imre Teaching Hospital, Budapest, Hungary; EGIS Pharmaceuticals PLC, Budapest, Hungary

Session:
Poster session 2

Citation:
European Heart Journal 2012;Vol.32(Abstract Supplement):240

Epidemiological data have shown that patients with clinical and preclinical stages of peripheral arterial disease (PAD) have high risk of cardiovascular mortality. By the measurement of the ankle/brachial index (ABI), PAD can be diagnosed in early asymptomatic stage. The objective of the present study was to evaluate the changes in blood pressure and serum cholesterol values during the first 3 years of the ERV program. A total of 21 892 hypertensive men and women (9162 males; mean age: 61.45 years) who were attended at 55 hypertension outpatient clinics in Hungary were included in our prospective study. Clinical history, physical examination, blood analysis, and measurement of the ankle-brachial index (calculated with the higher value at the ankle) were taken in all patients. Patients with established PAD (ABI ?0.9) were controlled annually. The prevalence of PAD was 14.4%. Mean systolic blood pressure in patients with an ABI?0.9 at visit 1 (baseline); visit 2; 3 and 4 were 143.69; 139.97; 139.72 and 140.11 mmHg, respectively (p<0.001 compared to baseline). Mean diastolic blood pressure at visit 1 (baseline); visit 2; 3 and 4 were 83.1; 81.26; 81.20 and 81.45 mmHg, respectively (p<0.001 compared to baseline). Mean serum cholesterol at visit 1 (baseline); visit 2; 3 and 4 were 5.34; 5.12; 4.99 and 4.94 mmol/L, respectively (p<0.001 compared to baseline). The use of ABI screening helps to identify patients at high cardiovascular risk and their treatment can be tailored according to the guidelines for high risk patients. Blood pressure and serum cholesterol values decreased significantly during the first 3 years of the ERV program. Cardiovascular morbidity and mortality data will be evaluated after the 5 years long prospective phase of the program.

[2012][P1617] Regional differences in the utilisation of coronary angiography as initial investigation for the evaluation of patients with suspected coronary artery disease

Authors:
I. Kosa, I. Vassanyi, A. Nemes, E. Belicza, G.Y. Kozmann.,Cardiac Rehabilitation Centre of Military Hospital, Balatonfüred, Hungary; Research & Development Center of Health Informatic Univ. Pannonia, Veszprem, Hungary; University of Szeged, Faculty of Medicine, 2nd Dept of Internal Medicine & Cardiology Center, Szeged, Hungary; Semmelweis University Health Services Management Training Center, Budapest, Hungary

Session:
Poster session 2

Citation:
European Heart Journal 2012;Vol.32(Abstract Supplement):248

Introduction: Despite diagnostic algorithm of patients with suspected coronary artery disease (CAD) is well defined, a considerable number of such cases reach the invasive procedures without previous noninvasive evaluation. In these subjects invasive evaluation is only based on the clinical characteristics. The present study was designed to depict regional differences in the utilisation of direct invasive evaluation strategy, and its consequences on the patient characteristics in Hungary.

Methods: Depersonalised data of 28.790 patients from the database of National Institute for Quality- and Organizational Development in Healthcare and Medicines of Hungary are included. All patients had undergone coronary angiography, as an initial investigation, following an at least half-year long stable period between 1st January 2004 and 31st December 2008. Patients with acute myocardial infarction were excluded from the evaluation. The activity of individual primary cardiological clinical centres were characterized by the data of patients living in the area supplied dominantly by the centre. For every centre with sample size above 100, the incidence of direct invasive investigations, and the age and mortality of these patients using the follow-up data until 31th december 2009 were calculated.

Results: From the 135 clinical centres 94 delivered above the predefined sample size of 100, covering 89.5% of the population of Hungary. Population size for the individual centres was 95.406±56.860 inhabitants (range 24.974 - 297.558). Coronary angiography was the initial investigation in 29.8±11.6 cases per 10.000 inhabitants (range 11.4 to 69.8). The mean age of this population was 61.4±13.6 years (range 56.2 - 69.2), while one-year mortality of these patients was 6.1±2.2% (range 1.9 - 15.9). Significant positive correlation was found between the incidence of the initial invasive procedure and the age of patients (R =0.40, p<0.001), while the mortality risk of patients tended rather to decrease with increasing incidence of direct invasive procedure (p =NS)

Conclusion: There are considerable differences in the utilisation of direct invasive procedures in the evaluation of patients with suspected CAD. The increasing number of this procedure is coupled with an increasing proportion of elderly subjects. The fact that the increase of age is not followed by increased mortality risk of involved patients suggests that one factor for greater incidence in some areas is the declined stringency in patient selection.

[2012][P1852] Percutaneous coronary intervention causes increased platelet - derived microvesicle release

Authors:
K. Vargova, Z.S. Horvath, E. Pallinger, S. Lee, A. Kovacs, E. Tothzsamboki, A. Falus, I. Preda, R.G. Kiss.,Military Hospital, Department of Cardiology, Budapest, Hungary; Semmelweis University, Department of Genetics, Cell- and Immunobiology, Budapest, Hungary

Session:
Poster session 2

Citation:
European Heart Journal 2012;Vol.32(Abstract Supplement):308

Purpose: Microvesicles (MVs) are membrane-derived microparticles originating mostly from platelets (platelet-derived microvesicles, PMV). The role of MVs in cardiovascular disease (CVD) or the effect of percutaneous coronary intervention (PCI) on MV release was not elucidated. Accordingly, we aimed to determine the early and long-term MV and PMV release after PCI performed in stable angina (SA) and to assess the effect of combined antiplatelet therapy (clopidogrel, aspirin) on MV and PMV absolute count.

Methods: We recruited 102 patients with SA undergoing elective coronarography. The direct and long – term effect of PCI was determined in forty - one stable angina patients (PC group). Individuals with negative coronarography (NC, n= 27) or those with positive coronarography, but without PCI (PC, n= 34) served as controls. The total microvesicle count (MV), platelet derived CD41+MV (PMV), P-selectin negative PMV (CD62P-/CD41+ PMV) and P-selectin positive PMV (CD62P+/CD41+ PMV) absolute count was determined by flow-cytometry. Blood samples were taken on admission, 24 hours, and 1, 3, 6,12 months thereafter. In each time point, platelet aggregation was assessed by Born-aggregometry (inductors: 5 micromol ADP, 10 micromol ADP, 1 microg/ml collagen, 2 microg/ml collagen, 0,5 microg/ml arachidonic acid, and 10 microg/ml epinephrin), as well.

Results: No significant difference in baseline absolute count of MV, PMV, CD62P-/CD41+ PMV and CD62P+/CD41+ PMV was found between the study groups. 24 hours after the PCI the MV (p<0.05), PMV (p<0.01) and P62+/41- PMV (p<0.05) absolute count showed significant increase compared to baseline levels. Diagnostic coronarography itself (PC, NC group) had no significant effect on the above parameters assessed at 24 hours. When analyzing patients according to the implanted stent type, the PMV (p<0.01), the P62-/41+ PMV (p<0.01) and the P62+/41+ PMV (p<0.05) absolute count at 6 months was significantly higher in the drug - eluting stent (DES) group compared to the bare metal stent (BMS) group. No significant correlation (Spearman correlation analysis) was found between the MV parameters, platelet aggregation values and the antiplatelet therapy.

Conclusion: Percutaneous coronary intervention evokes total microvesicle absolute count and - predominantly - P-selectin negative PMV absolute count elevation. This early systemic and platelet response is independent from platelet aggregation and is not influenced by combined antiplatelet treatment. At six months after PCI the PMV count was higher in case of DES implantation.div align="right">
Vissza a fejezet tetejére ^

[2012][P2429] Effect of paclitaxel-eluting balloon on physiologic vasodilatory capacity of porcine peripheral arteries, combined with safety and efficacy preclinical studies

Authors:
M. Gyongyosi, I. Sabdyusheva, V. Lamin, N. Pavo, E. Szentirmai, O. Petnehazy, Z. Petrasi, C. Plass, G. Maurer.,Medical University of Vienna, Vienna, Austria; University of Kaposvar, Kaposvar, Hungary

Session:
Poster session 2

Citation:
European Heart Journal 2012;Vol.32(Abstract Supplement):397

Purpose: Drug-eluting balloon (DEB) prevents neointimal hyperplasia in coronary arteries. In contrast to the muscular type coronary vessels, the peripheral (femoral and iliac) arteries are large elastic arteries, differing from coronaries by size, relative composition of elastic and muscle tissue and by physiologic functional properties. The present study was conducted to prove the safety and efficacy of the use of the paclitaxel (PTX)-coated peripheral percutaneous balloon FREEWAY (Eurocor, Germany) in prevention of neointimal hyperplasia and to investigate the vasomotor response of the peripheral arteries to DEB in comparison with plain balloon use.

Methods: Twenty-six domestic pigs underwent percutaneous FREEWAY overstretch balloon dilation (1.3:1 balloon/artery ratio) for 1 min of both iliac (balloon 6-7 mm of size, 40 mm of length) and femoral (balloon 5-6 mm of size, 40 mm of length) arteries using carotid access. Measurements of tissue PTX concentration (pre-clinical safety study) were performed by harvesting of the dilated arteries at 15 min, 1h, 3 and 9 days follow-up (FUP). The development of neointimal hyperplasia was measured by computerized planimetry 1 month after overstretch injury in a randomized pre-clinical efficacy study. The vasomotor response of the iliac and femoral arteries was determined after 5h, 1 and 7 days. During the FUP, the animals were treated with per os clopidogrel and aspirin.

Results: The achieved tissue PTX concentration showed a significant correlation with the applied balloon inflation pressure 1h post delivery in femoral arteries (r=0.597, p<0.05). The tissue PTX concentration was 433±122, 185±20, 4±1 and 1.4±0.5 ug/g in iliac, and 131±26, 54±8, 30±6 and 5.2±1.7 ug/g in femoral arteries at 15min, 1h, 3 days and 9 days post-dilation, respectively. The injury score was similar in all arteries. The degree of neointima was small in all peripheral arteries after overstretch injury, but the difference in neointimal area was significant: 0.24±0.03 vs 1.51±0.48 mm2 in femoral arteries and 0.62±0.24 vs 1.21±0.04 mm2 in iliac arteries treated with FREEWAY or plain balloon, respectively. In contrast to coronary arteries, use of DEB did not lead to addiction to vasoconstriction of the vessels, and no difference between the FREEWAY and plain balloon was observed regarding the impaired endothelium-dependent vasodilation capacity post-intervention.

Conclusion: FREEWAY DEB reduces effectively the neointimal hyperplasia in peripheral (iliaca and femoral) arteries, and does not lead to worse vasodilatory capacity as compared to plain balloon.

[2012][P2573] The potencial role of a PARP-inhibitor in the myocardial stem cell regeneration

Authors:
K. Magyar, I. Takacs, K. Bruszt, A. Balogh, K. Hideg, L. Seress, B. Sumegi, R. Halmosi, K. Toth. ,University of Pecs, Medical School, Heart Institute & 1st Dpt of Medicine, Div. of Cardiology, Pecs, Hungary; University of Pecs, Medical School, Medical Biology, Pecs, Hungary; Organic and Pharmacological Chemistry, Pecs, Hungary; Central Electron Microscope Laboratory, Pecs, Hungary; University of Pecs, Medical School, Department of Biochemistry and Medical Chemistry, Pecs, Hungary

Session:
Poster session 3

Citation:
European Heart Journal 2012;Vol.32(Abstract Supplement):433

Introduction: Ischemic myocardial damage leads to cell death, scar formation which determines the morbidity and mortality of postinfarction patients. It is known from literature that circulating stem cells deriving from bone marrow take a relevant part in myocardial regeneration. Previous examinations showed that thymosin beta-4 (TB4) occurs in embryonic heart, stimulates migration of cardiomyocytes, improves their survival and in adult heart it increases the mobilization of myocardial progenitor cells. It was also proved that TB4 exerts its favorable effect via the Akt-1 signal transduction pathway. The PARP-inhibitor L-2286 which was examined in several models by our group also exerts its protective effect via Akt pathway. Based on these evidences we assumed that L-2286 could enhance the expression of certain stem cell markers, for instance CD117 and CD133.

Methods: CD1 type mice were divided into 5 groups. Controls received placebo, the others 80 mg/kg isoproterenol (ISO) on the first day. On the 2nd day 6 mice received ISO, 6 mice ISO and 5 mg/kg L-2286, other 6 ISO, L-2286 and 150 ug thymosin, and the last group ISO and thymosin. 1 week later we examined the activation of different signal transduction pathways and the presence of stem cell markers CD117 and CD133 expression in hearts with confocal laser microscopy and Western-blot.

Results: Comparing control and ISO treated mice the number of CD117 positive cells increased significantly in the subepicardium and myocardium of the injured hearts. Activation of CD117 positive cells increased in L-2286 and in thymosin treated mice but the highest elevation could be seen in ISO, thymosin and L-2286 treated animals. This difference was also significant (p<0.05) using Western blot. Regarding CD133 positive cells we did not find any significant changes.

Conclusion: These results suggest that PARP inhibition via the activation of Akt-1 is able to affect stem cell renewal shortly after cardiac injury.

[2012][P3230] Transseptal endocardial left ventricular lead implantation, a highly effective alternative method for resynchronisation in selected cases

Authors:
L. Geller, L. Molnar, S.Z. Szilagyi, E. Zima, I. Osztheimer, G. Szeplaki, E. Vegh, T. Tahin, V. Kutyifa, B. Merkely., Semmelweis University, Cardiovascular Center, Budapest, Hungary

Session:
Poster session 4

Citation:
European Heart Journal 2012;Vol.32(Abstract Supplement):532

Transvenous left ventricular (LV) lead positioning might be challenging or in some instances impossible, in these cases alternative methods might be necessary. The aim of our study was to investigate the effectiveness and safety of transseptal endocardial left ventricular lead implantation in severe heart failure patients.

Objectives: Transseptal endocardial left ventricular lead implantation was performed in 22 patients (19 men, age: 62±9 years, NYHA III-IV stage).

Methods: Transseptal puncture was performed via the femoral vein using the standard approach. In those cases when transseptal puncture was difficult intracardiac ulrasound was used to guide the puncture. The site of the puncture was then dilated with a 6mm, later with an 8 mm balloon. After the puncture of the left subclavian vein, an electrophysiological deflectable CS catheter electrode was introduced into the CS sheath. The CS catheter was used to reach the left atrium and the left ventricle through the dilated transseptal puncture hole. In the left ventricle the latest activation (RLA) was determined. At the altest activation active fixation bipolar electrode was fixed into the wall of the left ventricle through the sheath.

Results: The lead was fixed in the left ventricle in all cases with good pacing threshold values (0,72±0,3 V;0,4 ms). Puncture complication, pericardial effusion was not detected. Because of anticoagulation therapy started immediately after the procedure, pocket haematoma was found in three cases, one of them needed evacuation. Follow-up is longer than one month in all patients (15,4±11 months). Significant improvement was observed in all but one case, on the first month control left ventricular ejection fraction was (28±6% vs 38±9%). Early lead dislocation was noticed in two cases, reposition was performed using the original puncture site in one, and transvenous implantation was succesfully carried out in the other case. Explantation of the system was necessary because of pocket infection in two cases, it was performed with simple traction only, no complication was noticed. In one of these cases transseptal biventricular ICD reaimplanattion was carried out succesfully 3 months after the explantation.

Conclusion: If transvenous and surgical epicardial method can not be applied, left ventricular endocardial electrode implantation might be a safe and effective alternative for implanting the left ventricular lead.

[2012][P3236] Effects of cardiac resynchronization therapy in heart failure patients, single-center experience, long-term follow-up

Authors:
V. Kutyifa, P. Bogyi, E. Zima, S.Z. Szilagyi, L. Molnar, I. Osztheimer, V.K. Nagy, G. Szeplaki, L. Geller, B. Merkely., Heart Center, Budapest, Hungary

Session:
Poster session 4

Citation:
European Heart Journal 2012;Vol.32(Abstract Supplement):534

Aim: To evaluate the long-term clinical outcome of CRT patients in a high-volume single-center experience of 11 years.

Methods: From 2000 to 2011,1122 CRT devices were implanted in our center. Clinical and echocardiographic data were collected before and after CRT implantation. Echocardiographic data available at last follow up (median 20 months, IQR: 10-38 months) were analyzed. Data on all-cause mortality was assessed based on clinic follow-up data and the Hungarian National Healthcare Fund Registry.

Results: 693 CRT-pacemakers and 429 CRT-ICD devices were implanted. The mean age of the patients was 65±11 years (860 men). CRT induced significant shortening of QRS duration (163±28 vs. 131±25 ms; p<0,001), decrease in left ventricular end-diastolic and end-systolic diameters (EDD 64,6±9,9 vs. 63,4±10,6mm; p<0,001 ESD 54,0±10,3 vs. 52,2±11,9mm; p<0,001) in mitral regurgitation (2,3±0,9 vs.2,0±1,0; p<0,001) and in pulmonary artery systolic pressure (PASP: 45,8±13,2 vs. 41,9±12,5Hgmm; p<0,001). Significant improvement of left ventricular ejection fraction (27,9±7,0 vs. 34,5±10,0%; p<0,001) and NYHA functional class (3,2±0,7, vs. 2,3±07; p<0,001) was observed. During the median follow-up of 28 months (IQR: 12-47) 379 patients died of any cause. The 5-year cumulative survival was 56% in the total patient population. Cumulative survival analysis did not reveal significant differences in the outcome among CRT pacemaker or CRT ICD patients (p=0.537). Figure 1. Cumulative Probability of Death

Conclusion: CRT is associated with significant clinical and echocardiographic improvement sustained during long-term follow-up. In this patient cohort, there was no difference in the outcome among CRT pacemaker or CRT ICD patients.

[2012][P3322] Recurrent restenosis after drug-eluting stent implantation for bare metal in-stent restenosis

Authors:
B. Berta, G.Y. Barczi, D. Becker, L. Geller, Z. Jambrik, L. Molnar, Z. Ruzsa, G.Y. Szabo, B. Merkely., Semmelweis University, Heart Center, Budapest, Hungary

Session:
Poster session 4

Citation:
European Heart Journal 2012;Vol.32(Abstract Supplement):556

The long term efficacy of percutaneous coronary intervention (PCI) is decreased by the need for repeated revascularisations caused by in-stent restenosis (ISR). Although the incidence of restenosis in drug eluting stents (DES) implanted for ISR is low, these cases still represent a serious professional challenge.

Purpose: The aim of our study was to evaluate the long-term safety and efficacy of DES in the treatment of an unselected population of diffuse bare metal stent (BMS) ISR compared to the use of DES in patients with de novo coronary lesions.

Methods: We examined a population consisting of 514 patients who underwent DES implantation between January 2003 and October 2006 in our institute. A total of 201 consecutive patients received DES for treatment of BMS ISR. In the control group, 313 patients received DES for de novo coronary lesions. The mean age of the two groups was similar (63.0±10.0 vs. 63.3±11.0), the rate of diabetic patients was high in both groups (34.3% vs. 38.3%). The control group contained a higher number of patients with acute coronary syndrome compared to the ISR group (55.3% vs. 44.8%, p<0.05). All patients received aspirin and clopidogrel therapy for at least 12 months. Outcomes were calculated using propensity-score adjustment. The mean follow-up length was 45.6±21.5 months

Results: According to our results the incidence of ischaemia-driven target lesion revascularisation (TLR) was not significantly higher in the ISR group compared to the de novo group at 4 years (10.4% vs. 12.4%, p=0.490). The total all-cause mortality was lower in the ISR group at 4 years (7.4% vs. 14.7%, p=0.032) but the incidence of definite and probable stent thrombosis according to ARC criteria did not differ (1.9% vs. 1.6%, p=0.708). The characteristics of restenosis did not differ significantly either between the two groups: 44.4% of the lesions were focal, 19.4% diffuse, 13.9% diffuse-proliferative, while in 22.2% we found total occlusions. The first restenosis of the implanted DES was treated the same way in the two subgroups, in 33.3% balloon angioplasty, in 47.2% PCI with a new stent implantation, and in 8.3% ACBG was indicated. In 11.1% of the cases no additional revascularization was performed. Despite the successful acute result of in-stent restenosis treatment, repeated restenosis developed in 17.9% of the cases in the ISR group, and in 20.0% in the de novo group (p=0.572).

Conclusion: DESs are effective in treatment of ISR and the rate of additional TLR is acceptable compared with the use of DES in de novo coronary lesions. After re-interventions a significantly higher rate of TLR can be anticipated.

[2012][P3538] Wine consumption is not associated with subclinical or clinical atherosclerosis

Authors:
J. Tarjan., Regional Committee of the Hungarian Academy of Sciences, Veszprém, Szombathely, Hungary

Session:
Poster session 4

Citation:
European Heart Journal 2012;Vol.32(Abstract Supplement):613

Purpose: Several studies have shown that wine consumers contract myocardial infarction (MI) less frequently than abstinents. Since the cause of MI is atherosclerosis, it is obvious to suppose that also atherosclerosis (AS) is less frequent among wine consumers, leading to a lower incidence of MI and also of cardiovascular disease (CVD).

Methods: Data of wine consumer and abstinent inhabitants of the West Hungarian wine producing region (Sopron, Koszeg, Vaskeresztes) were studied. From 990 persons (males: 67, females: 33%) 520 were regular wine consumers, 276 occasional wine consumers and 194 were abstinent. Inhabitans aged 20-80 years having lived in the region for at least 10 years and consuming the locally produced red wine were included into the study. The known cardiovascular diseases were assessed by a questionnaire. Presence of AS was determined by ultrasound investigation of the carotid arteries. Criterion of AS was demonstration of at least one plaque in either carotid. Total polyphenol, red pigment content, free radical trapping and ORAC values of the wines consumed in the region were analysed. Statistical analysis was performed by MedCalc Version 10.3.1.0.

Results: See the tables below.Characteristics of wines of the region: total polyphenol: 3,3–2,7 mg/l, anthocyanin: 1704,6–745,3, free radical trapping value: 94,7–78,7%, ORAC value: 12978,3–8872,6.

Conclusion: Not development of AS but that of CVD is reduced by wine consumption, presumably by altering plaque stability.

[2012][P4133] ECG changes during hypothermia as potential markers of mortality of successfully resuscitated patients

Authors:
G. Apponyi, D. Pilecky, Z.S. Szelenyi, A. Horvath, S.Z. Szilagyi, K. Heltai, L. Geller, D. Becker, B. Merkely, E. Zima., Semmelweis University, Heart Center, Budapest, Hungary

Session:
Poster session 5

Citation:
European Heart Journal 2012;Vol.32(Abstract Supplement):700

Introduction: Therapeutic hypothermia (THT) is the therapy of choice to improve neurologicoutcome and survival of patients remaining comatose after successful resuscitation. The reversible electrophysiologic changes induced by THT, e.g. bradycardia and prolongation of QT intervals, may increase the risk of malignant arrhythmias.

Methods: Our goal was to analyse the data of 32 patients treated with THT in the University from 01/01/2009 to 30/11/2010. We compared the heart rate, PQ, QRS, QT and corrected QT (QTc) intervals measured during THT (on 32-34°C) to those of during normothermia(NT), and relationship among survival and these factors was analysed by Cox regression. The meanage of the 25 male and 7 female patients was 64 (SD:12) years, the mean follow-up time was 139days.

Results: The 1 year survival was 40%. Between THT and NT the following significant differences werefound: heart rate: 71±21 vs 90±19 1/min; PQ: 183±32 vs 156±31 ms; QT: 488±79 vs 409±76 ms.The QRS and QTc intervals did not differ significantly. The mortality correlated significantly with thefollowing electrophysiologic changes: the rhythm other than sinus rhythm during THT (84.4% sinusrhythm and 15.6% other rhythm, p=0.012, HR:6.85, CI:1.52-30.8), QRS width during THT (117±24ms, p=0.014, HR:1.022, CI:1.004-1.04), and PQ interval during NT (159±38 ms, p=0.030, HR:1.013,CI:1.001-1.025). Two cases of ventricular fibrillation (VF) occurred during the THT, but neither a newreversible cause nor a prolonged QTc interval were found in the background, and the presence of VFdid not influence the short-term survival.

Conclusion: According to our low case number study, the PQ-, QRS-intervals and the rhythm at THTmay be potential markers of higher mortality, but the ECG changes between THT and NT did notinfluence the development of further VF, so THT can be safely applied during postresuscitation care.

[2012][P4529] Differing relations of the clinical responder rate to the left ventricular reverse remodelling and changes in left ventricular filling pattern in patients receiving cardiac resynchronization therapy

Authors:
M. Dekany, G. Zoltan, B. Szabo, B. Muk, B. Ancsin, T. Borsanyi, G.Z. Duray, R.G. Kiss, N. Nyolczas.,Military Hospital, Budapest, Hungary

Session:
Poster session 5

Citation:
European Heart Journal 2012;Vol.32(Abstract Supplement):801

Background: Clinical responder rate (CRr) and left ventricular (LV) reverse remodelling (RR) are regarded valuable markers of long-term favourable effects of cardiac resynchronization therapy (CRT). Besides the aforementioned parameters, the improvement of LV diastolic function (LVDF) might also be another valuable predictor of the long-term response to CRT.

Aim: To assess the relation of the CRr to the LVRR and to the improvement of LVDF evaluated by improvement in LV diastolic filling pattern (iLVFP) in pts receiving CRT. To investigate the survival of pts according to RR and iLVFP.

Patients and methods: 139 pts with CRT-P (51%) or CRT-D (49%) followed prospectively for 38.8±23.8 months. Age:64.1±10.6 years, male:81.2%, ischemic:37.4%, diabetes mellitus:35.4%, atrial fibrillation:23.6%, NYHA:2.8±0.8, blood pressure:116.4±21.6/72.6±12.8mmHg, LV ejection fraction (LVEF): 26.3±6.2%, LV enddiastolic diameter (LVEDD):74.2±8.8mm, grade of mitral regurgitation:1.7±0.9, estimated GFR:58.1±22.3ml/min/1.73m2, QRS width:159.9±32.4ms, left bundle branch block: 89.4%. Treatment: beta-blockers 95%, ACEi-s/ARBs:95%, aldosterone antagonists:71%, direct vasodilators:72%, furosemide:89%, digoxin:33%.

Results: The cumulative survival rate at 1, 2 and 3 years: 97.8%, 92.5% and 78.6%, respectively. CRr (alive, improved?1 NYHA, and not hospitalized): at 6 months 82%, at 12 months 78%. RR (LVEF increases?5% and LVEDD decreases?5%): at 6 months 36.8%, at 12 months 40.4%. iLVFP (deceleration time increases?10% and E/A decreases?10%): 35.8% at 6, and 34.4% at 12 months. Investigation of the relations between the aforementioned parameters showed, that iLVFP correlated significantly (p<0,05) to CRr, while no correlation was found between RR and CRr. iLVFP was associated with 100% of CRr, in lack of iLVFP CRr was 54.1%. Either in presence, or in absence of RR, the CRr was almost the same, i.e. 82% and 76%, respectively. Differences between surviving and not surviving pts according to RR and iLVFP, were nearly the same: in surviving pts RR in 37.5%, iLVFP in 39.7%, in not surviving pts RR in 17.1%, iLVFP in 16.1%. However these differences did not reach the level of significance: p=0.102 and 0.092 for RR and iLVFP, respectively.

Conclusion: In the effect of CRT, CRr and LVRR were not concordant with each other. On the other hand, the changes in LV diastolic filling pattern significantly correlated with CRr. Besides RR, the changes in LVDF may have a value also in predicting the long-term effect of the CRT on clinical outcome. Investigation its value in a larger pts' population seems to be reasonable.

[2012][P4732] Treatment of patients with inappropriate sinus node tachycardia: If-channel inhibition or ablation?

Authors:
J. Borbola, P. Abraham, C.S. Foldesi, A. Kardos., Gottsegen György Hungarian Institute of Cardiology, Budapest, Hungary

Session:
Poster session 6

Citation:
European Heart Journal 2012;Vol.32(Abstract Supplement):824

Inappropriate sinus node tachycardia (IST) is a relative rare clinical syndrome defined as increased sinus rate at rest, and/or inadequate response to physical or emotional stress without any underlying disease. In the last years 25 patients (23 women, 2 men; age: 18-57 (33) years) were treated with IST due to palpitations. Patients had no structural heart disease (EF: 65±2%), TSH values were within normal limits, but resting heart rate were repeatedly high: 106±3/min. The results of Holter recording (expressed as minimal-maximal and average heart rate/min) without medication showed high heart rate values: 58±2 - 163±3 - (96±2)/min. The bicycle ergometry showed an average loading capacity of 120±5W (heart rate: control (C): 104±/min, top (T): 170±6/min). The aim of the study was to evaluate the efficacy and safety of a selective sinus node If channel inhibitor drug, the ivabradine in the IST patient group. The ivabradine therapy decreased the heart rate significantly and dose-dependently compared to the control values: ivabradine: 2x5 mg/day: 50±2 - 131±5 - (76±2)/min (p<0.0001), ivabradine 2x7.5 mg/day: 48±1 - 130±6 - (72±2)/min (p<0.0001), and decreased the heart rate during ergometry: ivabradine: 2x5 mg/day: C: 83±3; T: 137±4/min (p<0.001), 2x7.5 mg/day: C: 77±4; T: 136±8/min (p<0.001). The loading capacity improved but did not change significantly (135±6W; ns). The ivabradine treatment was well tolerated, there was no sinus bradycardiac episode. All patients experienced symptom relief, three patient suffered from phosphenes, which completely resolved in a few days. Based on our clinical experiences IST can be treated with the sinoatrial node modulator drug ivabradine successfully and safely. Ivabradine significantly decreased, improved heart rate frequency spectrum and clinical symptoms. The disadvantage of the ivabradine is the lack of approval for IST therapy and the contraindication during pregnancy. During ivabradine treatment there was no indication for sinus node transcatheter ablation. Before the ablation of the sinoatrial node with the inherent risk of pacemaker implantation a clinical trial with ivabradine is suggested.

[2012][P4839] Relationship between three-dimensional speckle-tracking echocardiography-derived left ventricular rotation and twist and aortic stiffness

Authors:
A. Nemes, A. Kalapos, P. Domsik, C. Lengyel, A. Orosz, T. Forster. 2nd Department of Medicine and Cardiology Center, University of Szeged, Szeged, Hungary; 1st Department of Medicine, University of Szeged, Szeged, Hungary; Department of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, Hungary

Session:
Poster session 6

Citation:
European Heart Journal 2012;Vol.32(Abstract Supplement):851

Introduction: Left ventricular (LV) twist is the wringing motion of the heart, and has an important, but not fully evaluated role in the systolic and diastolic LV function. LV twist is the result of clockwise rotation of the LV base and counterclockwise rotation of the LV apex. It is well-known that stiffening of the aortic wall leads to changes in blood pressures compromising coronary perfusion and LV function. Three-dimensional (3D) speckle-tracking echocardiography (3DSTE) is a new clinical tool with which LV rotational and twist parameters could be quantified non-invasively. The present study was designed to find a relationship between 3DSTE-derived LV rotation and twist and echocardiographic aortic elastic properties in healthy subjects.

Methods: The present study comprised 26 healthy volunteers (mean age: 36.0±11.3 years, 13 men). All subjects had undergone complete 2-dimensional Doppler echocardiographic study extended with aortic stiffness measurements and 3DSTE. From 3D datasets basal and apical LV rotation and LV twist were assessed. Echocardiographic aortic stiffness parameters were calculated from systolic and diastolic ascending aortic diameter and blood pressure data.

Results: Mean aortic strain (0.131±0.094), aortic distensibility (3.61±2.54 cm2/dynes 10(-6)) and aortic stiffness index (ASI) (4.08±0.79) were in normal range, as well as basal (-2.42±1.43 degrees) and apical LV rotation (8.56±1.43 degrees) and LV twist (11.01±5.19 degrees). Apical LV rotation correlated with aortic distensibility (r =-0.36, p<0.05) and ASI (r =0.41, p<0.05), while LV twist showed similar correlation with ASI (r =0.42, p<0.05).

Conclusion: Correlations exist between 3DSTE-derived apical LV rotation and LV twist and echocardiographic aortic elastic properties in healthy volunteers.

[2012][P5002] Evaluation of the relationship between aortic elasticity and insulin sensitivity in healthy subjects with a normal carbohydrate metabolism

Authors:
R. Takac, A. Nemes, H. Gavaller, A. Orosz, T. Varkonyi, I. Foldesi, T. Wittmann, T. Forster, C. Lengyel., University of Szeged, Faculty of Medicine, 1st Dept of Internal Medicine, Szeged, Hungary; University of Szeged, Faculty of Medicine, 2nd Dept of Internal Medicine & Cardiology Center, Szeged, Hungary; University of Szeged, Faculty of Medicine, Department of Pharmacology & Pharmacotherapy, Szeged, Hungary

Session:
Poster session 6

Citation:
European Heart Journal 2012;Vol.32(Abstract Supplement):894

Aortic elasticity is an independent predictor of the cardiovascular morbidity and mortality. It has been demonstrated that aortic elasticity might be decreased in type 2 diabetes mellitus. The aim of this study was to determine the correlations between aortic elasticity and insulin sensitivity in healthy subjects with a normal carbohydrate metabolism according to the WHO criteria.

Materials and methods: 21 healthy subjects (12 women and 9 men, age: 40.6±2.5 years, BMI: 24.4±1.0 kg/ms2, systolic blood pressure: 130.7±3.6 mmHg, diastolic blood pressure: 76.9±2.3 mmHg, fasting plasma glucose: 4.8±0.1 mmol/l, fasting insulin: 7.9±1.0 mIU/l, HOMA-A: 1.7±0.2; mean±SD) were enrolled into the study. Transthoracal echocardiography was used for the determination of aortic elasticity. It was characterized by aortic distensibility (AD), aortic stiffness index (ASI) and aortic strain (AS) which were calculated using aortic ascendens dimensions (systolic and diastolic diameters) measured during transthoracal echocardiography and blood pressure. The relationships between parameters were analysed by linear regression model. Statistical analysis was performed by SPSS program.

Results: There were statistically significant negative correlations between HOMA-A and AD (r=–0.689, p=0.001) and AS (r=–0.663, p=0.001). The correlation between HOMA-A and ASI (r=0.770, p=0.00005) was positive. The results were same between fasting insulin level and relevant aortic parameters (AD: r=–0.705, p=0.0004; AS: r=–0.663, p=0.001; ASI: r=0.723, p=0.0002). There was no significant correlation between the fasting plasma glucose and aortic elasticity.

Conclusion: Our results revealed a close relationship between decreased insulin sensitivity within the normal range and aortic stiffness in healthy subjects which may forecast the early cardiovascular adaptation damage.

[2012][P5011] Cost-effectiveness of cardiac resynchronization therapy in combination with an implantable cardioverter defibrillator in mild heart failure based on Markov modeling using UK cost approach in MADIT CRT

Authors:
V. Kutyifa, P. Aidelsburger, S. Schauer, B. Merkely, H. Klein, M. Kuniss, A. Kloppe, T. Kayser, R. Peppa, A.J. Moss. Heart Center, Budapest, Hungary; CAREM GmbH, Sauerlach, Germany; University of Rochester Medical Center, Cardiology Division, Rochester, United States of America; Kerckhoff Clinic, Bad Nauheim, Germany; Maerkische Kliniken GmbH, Klinikum Luedenscheid, Luedenscheid, Germany; Boston Scientific Corp., Brussels, Belgium

Session:
Poster session 6

Citation:
European Heart Journal 2012;Vol.32(Abstract Supplement):896

Aim: To evaluate the cost-effectiveness of CRT-D in mild heart failure LBBB or female patients enrolled in the Multicenter Automatic Defibrillator Implantation Trial – Cardiac Resynchronization Therapy (MADIT-CRT).

Methods: A decision analytic Markov model was created to evaluate the costs, gained life-years and quality-adjusted life years (QALYs) associated with CRT-D compared to ICD treatment. Analysis was performed in 1281 LBBB patients and in 453 females enrolled in MADIT-CRT from the perspective of the United Kingdom National Health Service. Costs and utilities were discounted at 3.5% per year. Base-case analysis and multiple one-way sensitivity analyses were performed.

Results: Compared with ICD treatment, CRT-D gained 1.51 QALYs having a cost of €19.855 in LBBB patients, resulting in an incremental cost-effectiveness ratio (ICER) of €13.147 per QALY gained when using a life-time horizon of 35 years. The female population gained 3.81 QALYs at an additional cost of €30.088 resulting in an ICER of €7.898. ICER implemented for a 10-year time-period was €14.282 for LBBB patients, €8.313 for female patients, respectively. One-way sensitivity analyses revealed the discount rate and the utility per cycle without heart failure events to be the most sensitive variables for cost-effectiveness.

Conclusion: CRT-D treatment is cost-effective in mild heart failure LBBB or female patients with severely depressed left ventricular ejection fraction and a wide QRS when compared to ICD only, for a 10-year and 35-year time horizon.

[2012][P5121] Left ventricular diastolic and systolic and atrial dysfunction in patients with hypertension might be related to increased oxidative stress and inflammation-final results

Authors:
Z.S. Szelenyi1, G. Szenasi2, M. Kiss3, Z. Prohaszka3, A. Patocs4, A. Fazakas3, I. Karadi3, A. Vereckei3. 1Semmelweis University, Heart Center, Budapest, Hungary; 2Semmelweis University, Institute of Pathophysiology, Budapest, Hungary; 33rd Department of Internal Medicine, Semmelweis University School of Medicine, Budapest, Hungary; 4Semmelweis University, 2nd Department of Internal Medicine, Budapest, Hungary

Session:
Poster session 6

Citation:
European Heart Journal 2012;Vol.32(Abstract Supplement):926

Purpose: To study the presence of oxidative stress, inflammation, hypercoagulability and neuroendocrine activation in patients with hypertension (HT).

Methods: Results from ?60-year-old 112 patients (18 controls and 94 patients with HT) with normal ejection fraction (EF) are presented. All subjects had echocardiography with assessment of atrial and left ventricular (LV) systolic and diastolic function. Determination of (1) oxidative stress [measurement of total scavenger capacity (TSC), protein carbonylation (PK), tetrahydrobiopterin (BH4) levels], (2) inflammatory [measurement of C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor-? (TNF-?) levels], (3) coagulation [measurement of fibrinogen levels, plasminogen activator inhibitor-I (PAI-I) and von Willebrand factor] and (4) neuroendocrine parameters [chromogranin A (cGA) and B-type natriuretic peptide (BNP) levels] was carried out from plasma or serum samples.

Results: 38/94 (40%) patients with HT had no diastolic dysfunction (HTDD- group), and 56/94 (60%) patients had diastolic dysfunction (HTDD+ group). TSC decreased and BH4 increased in both patient groups (p<0.001 and p<0.01 for both groups respectively), PK increased (p<0.05) in the HTDD- group, CRP increased (p<0.05) in the HTDD+ group, and IL-6, TNF-?, PAI-I, cGA, BNP increased (p<0.001 and p<0.05; p<0.05 for both groups; p<0.001 for both groups; p<0.05 and p<0.01; p<0.05 and p<0.01 respectively) in both patient groups compared with controls. No between groups difference was found in other laboratory parameters. The absolute values of the mean of maximal longitudinal systolic LV strain (S) (p<0.05 for both groups) and systolic (p<0.001 for both groups) and early diastolic (p<0.05 for HTDD- and p<0.001 for HTDD+ groups) strain rates (SR) and those of atrial contraction period (p<0.05 for both groups) and atrial reservoir period (p<0.001 for both groups) SRs in both patient groups were reduced compared with controls. Numerous significant correlations between biochemical and echocardiographic parameters were found. Typically the degree of oxidative stress and inflammation, BNP and PAI-I levels correlated inversely with LV systolic and diastolic and atrial function.

Conclusion: In patients with HT and normal EF, the most common precursor of heart failure with preserved EF, oxidative stress [partly might be due to myocardial nitrogen oxide synthase (NOS) uncoupling, as indicated by the increased plasma NOS cofactor BH4 level, which is usually associated with decreased tissue BH4 levels] and inflammation might have a role in LV systolic and diastolic and atrial dysfunction.

[2012][P5347] Percutaneous intramyocardial delivery of secretome of apoptotic white blood cells (APOSEC) improves myocardial viability and left ventricular function in experimental ischemic cardiomyopathy

Authors:
M. Gyongyosi1, M. Zimmermann1, N. Pavo1, M. Mildner1, O. Petnehazy2, Z. Petrasi2, E. Szentirmai2, G. Maurer1, J. Ankersmit1. 1Medical University of Vienna, Vienna, Austria; 2University of Kaposvar, Kaposvar, Hungary

Session:
Frontiers in basic science

Citation:
European Heart Journal 2012;Vol.32(Abstract Supplement):981

Purpose: Despite promising preclinical and clinical results of the cell-based therapy in chronic ischemic heart failure, the achievable benefit still remains suboptimal. We have previously shown the regenerative capacity of the secretome of the apoptotic white blood cells (APOSEC) in acute myocardial infarction (AMI). In the present experiment we have investigated the effect of Aposec on the ventricular function and ischemia in experimental ischemic cardiomyopathy.

Methods: Closed chest reperfused AMI was induced by 90-min occlusion of the mid left anterior descending coronary artery in 14 domestic pigs, followed by baseline cardiac MRI at day 3. One month later (day 30), the animals were randomized and received either porcine APOSEC (n=7) or control Medium (n=7) using the 3D NOGA percutaneous intramyocardial injection technique in the periinfarction areas (10-13 treatment locations). After 1-month follow up (FUP) (day 60), control cardiac MRI with late enhancement and measurements of myocardial viability via diagnostic electroanatomical mapping were performed. Gene expression of the infarction border zone and the necrotic areas were evaluated and post hoc validation of genes identified bymicroarray was performed by using quantitative TaQMan real-time polymerase chain reaction.

Results: APOSEC led to an improvement of left ventricular (LV) ejection fraction (45±6% vs 38±9%), cardiac index (4.1±0.4 vs 3.32±0.3 L/min) and myocardial viability in the injected myocardial area (10.1±3.0 vs 8.7±7.1 mV; p<0.05). Trend towards decrease in size of myocardial scar was observed in Aposec group (20±18 vs 33±29% of the LV), as compared with the Medium group. Gene profiling analysis revealed robust significant upregulation of stem cell homing (cadherin, CXCR4 and stromal-derived factor-1) and some angiogenic factors (such as cathepsin) and myogenic genes expressing myosin and actin in the injected areas of the Aposec group, as compared with the Medium group. The angiogenic vascular endothelial, fibroblast or insuline-like growth factor gene expression was similar in both groups. In the infarcted area, the expression of matrix metalloprotease (MMP)-1 and MMP-12 and actin were significantly elevated in Aposec group, as compared with the Medium group.

Conclusion: “Cell-less cell therapy” seems to be effective in improvement of chronic cardiac ischemia and dysfunction, therefore might be a promising tool in treatment of ischemic cardiomyopathy preventing also LV remodeling.

[2012][P5415] Association of pre-operative complement C3a concentrations with the clinical outcome following cardiac resynchronization therapy

Authors:
G. Szeplaki1, Z.S. Jenei2, A. Kosztin1, E.M. Vegh1, S.Z. Szilagyi1, L. Molnar1, E. Zima1, L. Geller1, Z. Prohaszka2, B. Merkely1. 1Semmelweis University, Heart Center, Budapest, Hungary; 2Semmelweis University, 3rd Department of Internal Medicine, Budapest, Hungary

Session:
Poster session 7

Citation:
European Heart Journal 2012;Vol.32(Abstract Supplement):995

Biventricular pacing by cardiac resynchronization (CRT) therapy improves the clinical state of the majority of severe heart failure patients with intraventricular conduction delay. As some patients do not benefit from the therapy, the need for pre-operative identification of non-responders is emerging. Previously we have described, that the complement system might play an important role in the pathogenesis of heart failure and complement anaphylatoxin C3a is independently associated with disease severity. Our aim was to determine the predictive value of complement components and inflammatory markers on the clinical outcome following CRT. One-hundred forty-seven patients on optimal medical therapy with wide QRS (?120 ms), NYHA II-IV class severe heart failure and decreased LVEF (<35%) were included in this prospective study. Primary endpoint was cardiovascular mortality or heart transplantation; secondary endpoint was responder state at 6 months following CRT implantation (at least one class improvement on the NYHA state or at least 10% improvement on the 6 minutes walking distance). Complement components (C3, C3a, sC5b-9) inflammatory proteins (C-reactive protein – CRP, tumor necrosis factor-?– TNF-?) and B-type natriuretic peptide (NT-pro-BNP) were determined preoperatively. Patients who met the primary end point had significantly higher C3a concentrations (302.7 [236.2-373.7] vs. 189.9 [140.2-255.8] ng/ml; p=0.001). High C3a levels predicted mortality and heart transplantation with an odds ratio of 3.5 (95% confidence interval 1.2-10.7; p=0.038). Levels of CRP and NT-proBNP were also higher in patients meeting the primary endpoint (p=0.004 and p=0.028), however these markers did not have significant predictive value (p=0.101 and p=0.069). C3a was the only marker which was elevated in patients who met the combined primary and secondary end point (mortality or heart transplantation or non-responder clinical state: 228.8 [181.6-324.6] vs. 191.9 [141.7-263.9] ng/ml; p=0.013). We found no association between TNF-?, sC5b-9 or total C3 levels and the clinical outcome. According to our results, complement activation is strongly linked to unfavourable outcomes in heart failure. C3a may be a promising marker in the prediction of clinical response following CRT. Anaphylatoxin C3a might have a direct causative role in the progression of heart failure by edema formation due to increased fluid extravasation. Determining C3a concentrations preoperatively might improve the efficacy of appropriate patient selection. Grants: TAMOP-4.2.2./B10/1.-2010-0013; TAMOP-4.2.2-08/1/KMR-2008-0004.

[2012][P5527] The distribution of myocardial ischemia on stress perfusion SPECT studies in relation with the fractional flow reserve

Authors:
C.S. Jenei1, B. Kracsko2, I. Racz1, G.T. Szabo1, F. Gyory1, G. Vajda1, I. Edes1, Z.S. Koszegi1. 1University of Debrecen, MHSC-Faculty of Medicine, Institute of Cardiology, Department of Cardiology, Debrecen, Hungary; 2University of Debrecen, MHSC-Faculty of Medicine, Department of Nuclear Medicine, Debrecen, Hungary

Session:
Poster session 7

Citation:
European Heart Journal 2012;Vol.32(Abstract Supplement):1025

Background: According to the current guideline the 17 myocardial segments can be assigned to the 3 major coronary arteries. However, the individual coronary artery variation can differ significantly from the standardized assignment. This can explain the recently published disagreements between the results of the fractional flow reserve (FFR) and the perfusion abnormality on the scintigrams (SPECT).

Aim: To generate an algorithm about the concordance between the individual epicardial coronaries and the left ventricular segments on the basis of the coronary angiography, and to compare the overlap between the FFR-predicted ischemic segments and the segments with reversible perfusion defect on the SPECT according to the assignment in our algorithm and on the basis of the guideline.

Method: Data of 29 patients with at least one angiographycally significant lesion (>50% diameter stenosis) and with FFR measurements by intracoronary pressure wire and stress perfusion studies were analyzed. The distribution of the ischemia defined by ? 1 reversibility score/segment (RSc) on the perfusion polar map was correlated with the individual lesion-associated (L-A) left ventricular segments defined by our algorithm called Holistic Coronary Care (HCC) program. The software used the modified Syntax segmentation for defining the L-A left ventricular region in the 17 segment model.

Results: In the HCC program 2-11 left ventricular segments (altogether 87) were assigned to the 14 FFR positive (<0.80) stenoses on the basis of the coronary angiography. Out of these segments 56 showed reversible perfusion defect. From these data the per-vessel analysis using the regional ischemia criteria (? 2 RSc) showed 65% sensitivity and 100% specificity for the prediction of ischaemia by the HCC and 59% sensitivity and 82% specificity for the prediction of ischaemia by the standard alignment. Per-segment analysis revealed 78% sensitivity and 84% specificity, by the HCC and 44% sensitivity and 86% specificity for the prediction of ischaemia by the standard alignment, respectively.

Conclusion: The myocardial segments affected by significant epicardial lesions can be defined higher sensitivity by the HCC program than on the basis of the standard alignment.

[2012][P5775] Obesity paradox: the impact of body mass index on short- and mid-term mortality in patients with acute coronary syndrome

Authors:
D. Becker1, O. Balogh1, A. Hajas1, G.Y. Barczi1, G.Y. Szabo1, A. Nagy1, A. Apor1, E. Zima1, K. Heltai1, B. Merkely1. 1Semmelweis University Heart Center, Budapest, Hungary

Session:
Poster session 7

Citation:
European Heart Journal 2012;Vol.32(Abstract Supplement):1088

Introduction: Although obesity seems to be an independent risk factor of cardiovascular diseases, recently data suggests lower risk of short-term mortality in obese patients with acute coronary syndrome.

Objective: To investigate the obesity paradox in obese patients with acute coronary syndrome, receiving percutaneous intervention treatment in a high volume interventional heart center.

Method: Between 01.01.2009 and 31.12.2010 all together 2305 patients were consecutively enrolled to the study. Obesity paradox was investigated according to the short- and mid-term survival data and BMI of the patients. Statistical analyses were performed using ?2 test and logistic regression.

Results: Patients were divided into 4 groups based on BMI: less than 20 (underweight, n=78); 20-24.9 (normal, n=651), 25-29.9 (overweight, n=897),>30 (obese, n=677). We considered normal weight group as a basis for comparison. There was no difference in the number of STEMI patients among the different groups (44/56, 4%; 346/53, 1%; 434/48, 4%; 325/48, 0%). Proportion of female patients was significantly higher in the underweight group and significantly lower in the overweight and obese group (54/69, 2%; 280/43, 0%; 290/32, 3%; 252/37, 2% p<0.001). Age in obese group was significantly lower (72,8±14,5; 69,1±13,9; 67,8±12,5; 64,7±11,4 p<0.001) with higher incidence of diabetes (2/2, 60%; 33/5, 10%; 65/7, 20%; 65/9, 60% p=0.002). At 30 days and at 6 months mortality of overweight group was significantly lower, compared to the normal weight group (30 days: 52/897, 5,8%; 60/651, 9,2% p=0,036; 6 month: 127/651, 19,6%; 116/897, 12,9% p<0.001). In case of obese patients, there was no difference in the 30 days survival (mortality: 43/677, 6,4%; 60/651,9, 2% p=NS) but life expectancy at 6 months was significantly better (mortality: 76/897, 11,2%; 127/651, 19,6%; p=0.032).

Conclusion: We assume that “Obesity Paradox” seems to be a real phenomenon in our patients after acute coronary syndrome. Mid-term prognosis for overweight and obese patients is better in this setting, compared to the normal weight individuals.

[2012][3100] Fibrinolytic activity of human cardiac endothelial cells; effect of nerve growth factor

Authors:
J. Skopal1, N. Hegyesi1, E. Szigetfu1, Z.S. Lendvai1, M. Polos2, F. Horkay2, Z. Nagy1, B. Merkely1. 1Semmelweis University, Heart Center, Budapest, Hungary; 2Semmelweis University, Departmen of Cardiac Surgery, Budapest, Hungary

Session:
Endothelial function as a therapeutic target

Citation:
European Heart Journal 2012;Vol.32(Abstract Supplement):512

Purpose: While the predominant role of neurotrophic factors in the neuronal system is un-questoned, recent observations indicate that these factors also have direct effect on blood vessel system. Neurotrophins and their receptors are essential regulators in the formation of the heart and in the vascular development. Neurotrophins control the survival of endothelial cells (ECs), vascular smooth muscle cells, cardiomyocytes and regulate angiogenesis. ECs modulate fibrinolysis via production of tissue- and urokinase-type plasminogen activators (tPA and uPA) and their inhibitor (PAI-1). PAs partly bound to the cell surface resulting plasmin generation. In this way ECs participate in the removal of local fibrin clots. In our work we investigated the effect of nerve groth factor (NGF), the representative member of neurotrophins family, on the fibrinolytic activity of cultured human cardiac capillary endothelial cells (HCECs). We used human brain capillary endothelial cells (HBECs) as controll.

Method: ECs were incubated with or without NGF (1-1000 ng/mL) for 72 hours. In media tPA, uPA and PAI-1 proteins were measured by ELISA. Plasmin generation on cell surface and in cell culture media was followed by plasmin specific chromogen substrate. The direct fibrinolytic activity of media was visualized on fibrin plate. Plasminogen protein was immundetected by Western blotting.

Results: Plasmin was generated on the surface of HCECs and HBECs in a time dependent manner (1mCU/mL vs. 2 mCU/mL during 1 hour). PAI-1 and tPA levels were in the same concentration range in media of both cells (500-1000 ng/mL and about 1 ng/mL, respectively). The uPA concentration was higher in HBECs media than in HCECs media (3-5 ng/mL vs. 0,5-2,5 ng/mL). NGF treatment was ineffective on plasmin generation and protein expressions. NGF treatment did not influence the plasmin generation in HBECs media. In HCECs media plasminogen was activated to plasmin in NGF-dose dependent manner. However, in media of both cells plasmin generation was detected in absent of plasminogen as well and plasmin activity was completely blocked by aprotinin (20 KIE/mL). The NGF treated media lysed fibrin directly on fibrin plates. Plasminogen protein was visualized after 100 ng/mL NGF treatment by Western blot.

Conclusion: Our direct plasmin generation and fibrin lysis assays suggest that NGF induces plasminogen expression in ECs. These results provide a new mechanistic insight into the vascular effect of NGF.