IKEM

Prague, Czech Republic
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Trunecka P.,IKEM | Boillot O.,Hopital Edouard Herriot | Seehofer D.,Klinik Transplantationschirurgie | Pinna A.D.,University of Bologna | And 5 more authors.
American Journal of Transplantation | Year: 2010

The efficacy and safety of dual-therapy regimens of twice-daily tacrolimus (BID; Prograf) and once-daily tacrolimus (QD; Advagraf) administered with steroids, without antibody induction, were compared in a multicenter, 1:1-randomized, two-arm, parallel-group study in 475 primary liver transplant recipients. A double-blind, double-dummy 24-week period was followed by an open extension to 12 months posttransplant. The primary endpoint, event rate of biopsy-proven acute rejection (BPAR) at 24 weeks, was 33.7% for tacrolimus BID versus 36.3% for tacrolimus QD (Per-protocol set; p = 0.512; treatment difference 2.6%, 95% confidence interval -7.3%, 12.4%), falling within the predefined 15% noninferiority margin. At 12 months, BPAR episodes requiring treatment were similar for tacrolimus BID and QD (28.1% and 24.7%). Twelve-month patient and graft survival was 90.8% and 85.6% for tacrolimus BID and 89.2% and 85.3% for tacrolimus QD. Adverse event (AE) profiles were similar for both tacrolimus BID and QD with comparable incidences of AEs and serious AEs. Tacrolimus QD was well tolerated with similar efficacy and safety profiles to tacrolimus BID. © 2010 The American Society of Transplantation and the American Society of Transplant Surgeons.


Dukkipati S.R.,Mount Sinai School of Medicine | Kuck K.-H.,Asklepios Klinik St. Georg | Neuzil P.,Homolka Hospital | Woollett I.,Sentara Cardiovascular Research Institute | And 11 more authors.
Circulation: Arrhythmia and Electrophysiology | Year: 2013

Background-Because of the technical difficulty with achieving pulmonary vein (PV) isolation in the treatment of patients with paroxysmal atrial fibrillation, novel catheter designs to facilitate the procedure are in development. A visually guided laser ablation (VGLA) catheter was designed to allow the operator to directly visualize target tissue for ablation and then deliver laser energy to perform point-to-point circumferential ablation. Single-center studies have demonstrated favorable safety and efficacy. We sought to determine the multicenter feasibility, efficacy, and safety of performing PV isolation using the VGLA catheter. Methods and Results-This study includes the first 200 paroxysmal atrial fibrillation patients treated with the VGLA catheter (33 operators, 15 centers). After transseptal puncture, the VGLA catheter was used to perform PV isolation. Electric isolation was assessed using a circular mapping catheter. Using the VGLA catheter, 98.8% (95% confidence interval, 97.8%-99.5%) of targeted PVs were isolated using a mean of 1.07 catheters per patient. Fluoroscopy and procedure times were 31±21 (mean±SD) and 200±54 minutes, respectively, and improved with operator experience. There were no instances of stroke, transient ischemic attack, atrioesophageal fistulas, or significant PV stenosis. There was a 2% incidence of cardiac tamponade and a 2.5% incidence of phrenic nerve palsy. At 12 months, the drug-free rate of freedom from atrial arrhythmias after 1 or 2 procedures was 60.2% (95% confidence interval, 52.7%-67.4%). Conclusions-In this multicenter experience of the first 200 patients treated with the VGLA catheter, PV isolation can be achieved in virtually all patients using a single VGLA catheter with an efficacy similar to radiofrequency ablation. © 2013 American Heart Association, Inc.


Burri H.,University of Geneva | Quesada A.,University of Valencia | Ricci R.P.,San Filippo Neri Hospital | Boriani G.,University of Bologna | And 7 more authors.
American Heart Journal | Year: 2010

Background: With the advent of remote monitoring, current models of implantable cardioverter defibrillators (ICDs) have the possibility of sending automatic alert messages that allow early diagnosis of events such as lung fluid overload, atrial fibrillation and device integrity issues. Timely treatment of these events has the potential to improve patient outcome, but this has not as yet been proven. Methods: The MORE-CARE study is a multicenter randomized controlled trial evaluating the efficacy of advanced device diagnostics and remote monitoring in improving the outcome of patients with biventricular ICDs. Up to 1720 patients with a standard indication for a biventricular ICD will be randomized to standard in-office follow-up, or to a remote monitoring strategy using the CareLink network and involving automatic alerts for lung fluid overload, atrial fibrillation, and device integrity issues. The first phase aims at evaluating the delay between an alert event, and clinical action to the event. The second phase of the study will evaluate whether the remote monitoring strategy results in a significant reduction of a combined end point of total mortality or cardiovascular and device-related hospitalization. The duration of the study will be event-driven due to its sequential design. Conclusion: MORE-CARE will evaluate the efficacy of remote monitoring for improving patient outcome in patients implanted with a biventricular ICD. © 2010, Mosby, Inc. All rights reserved.


Vancura V.,Charles University | Wichterle D.,IKEM | Wichterle D.,Charles University | Melenovsky V.,IKEM | Kautzner J.,IKEM
Europace | Year: 2013

AimsRight ventricular apical pacing has a detrimental effect on left ventricular (LV) function. More optimal pacing site may be found by invasive measurement of LV mechanical performance during pacing from different RV pacing sites. We aimed to investigate the effect of RV pacing lead location on invasive indices of LV mechanical performance.Methods and resultsPatients undergoing catheter ablation for persistent atrial fibrillation were enrolled. Single-site endocardial pacing from the lateral LV region was periodically switched to pacing from the mapping catheter navigated to different RV sites within the three-dimensional electroanatomical RV map. SystIndex, DiastIndex, and PPIndex were defined as the ratio of LV dP/dtmax, LV dP/dtmin, and arterial pulse pressure during RV pacing to corresponding values from adjacent periods of LV pacing. Haemodynamic data were analysed in 18 RV segments created by dividing RV horizontally (basal, mid, and apical portion), vertically (inferior, mid, and superior portion) and frontally (septum and free wall). Eight patients (58 ± 7 years; 2 females; 26 ± 4 RV pacing sites per patient) were enrolled into the study. Compared with LV pacing, the best RV pacing values of SystIndex and DiastIndex were achieved in basal-mid-septal segment (+6.9%, P = 0.02 and +3.4%, P = 0.36, respectively) while the best PPIndex was obtained in superior-mid-septal segment of RV (+4.5%, P = 0.02). All indices were fairly concordant showing significant improvement of haemodynamics during RV pacing in the direction from free wall to septum, from apex to base, and from inferior to superior segments.ConclusionThe best LV mechanical performance was achieved by RV septal pacing in the non-apical mid-to-superior segments. © 2013 Published on behalf of the European Society of Cardiology. All rights reserved.


McLaughlin V.,University of Michigan | Channick R.N.,Massachusetts General Hospital | Ghofrani H.-A.,Justus Liebig University | Lemarie J.-C.,Effi Statistics | And 8 more authors.
European Respiratory Journal | Year: 2015

The safety and efficacy of adding bosentan to sildenafil in pulmonary arterial hypertension (PAH) patients was investigated. In this prospective, double-blind, event-driven trial, symptomatic PAH patients receiving stable sildenafil (≥20 mg three times daily) for ≥3 months were randomised (1:1) to placebo or bosentan (125 mg twice daily). The composite primary end-point was the time to the first morbidity/mortality event, defined as all-cause death, hospitalisation for PAH worsening or intravenous prostanoid initiation, atrial septostomy, lung transplant, or PAH worsening. Secondary/exploratory end-points included change in 6-min walk distance and World Health Organization functional class at 16 weeks, change in N-terminal pro-brain natriuretic peptide (NT-proBNP) over time, and all-cause death. Overall, 334 PAH patients were randomised to placebo (n=175) or bosentan (n=159). A primary endpoint event occurred in 51.4% of patients randomised to placebo and 42.8% to bosentan (hazard ratio 0.83, 97.31% CI 0.58-1.19; p=0.2508). The mean between-treatment difference in 6-min walk distance at 16 weeks was +21.8 m (95% CI +5.9-37.8 m; p=0.0106). Except for NT-proBNP, no difference was observed for any other end-point. The safety profile of bosentan added to sildenafil was consistent with the known bosentan safety profile. In COMPASS-2, adding bosentan to stable sildenafil therapy was not superior to sildenafil monotherapy in delaying the time to the first morbidity/mortality event. © ERS 2015.


Tringali A.,Catholic University | Didden P.,Erasmus Medical Center | Repici A.,IRCCS Instituto Clinico Humanitas | Spaander M.,Erasmus Medical Center | And 9 more authors.
Gastrointestinal Endoscopy | Year: 2014

Background Malignant gastric outlet obstruction is often treated by stent placement. Objective To investigate the outcomes of stent placement in the palliative treatment of malignant neoplasms. Design Prospective, observational, multicenter registry. Setting Six tertiary care centers in 5 countries. Patients A total of 108 adult patients with malignant gastric outlet obstruction. Interventions Placement of an uncovered, self-expandable, metal duodenal stent. Main Outcome Measurements The primary endpoint was stent patency at 14 days after stent implantation. Secondary endpoints included stent patency at 1, 2, 3, and 6 months, gastric outlet obstruction scoring system (GOOSS) scores at 14 days and 1, 2, 3, and 6 months after stent deployment, technical success, adverse events, and patient survival (ie, confirmed duration of the implant). Results Technical success was achieved in 99.1% of stent placements. Stent patency at 14 days was 94.6%. Kaplan-Meier estimates of stent patency were 92.9% at 1 month, 86.2% at 2 months, 81.9% at 3 months, and 63.4% at 6 months. At 14 days, GOOSS scores increased by a median of 1 point. The overall GI adverse event rate was 32.4%; however, the stent-related adverse event rate was 19.4%. The median implant duration was 47 days (range 0-195 days). Limitations Observational study, no control group. Conclusions Duodenal stent placement resulted in prompt relief of malignant gastric outlet obstruction and improved GOOSS scores. (Clinical trial registration number: NCT00991614.). Copyright © 2014 by the American Society for Gastrointestinal Endoscopy.


Van Hooff J.P.,Maastricht University | Alloway R.R.,University of Cincinnati | TruneccKa P.,IKEM | Mourad M.,Catholic University of Louvain
Clinical Transplantation | Year: 2011

Introduction: This study assessed the long-term effects of prolonged-release tacrolimus (Advagraf ® [Tacrolimus QD]), which has been developed to provide similar efficacy and safety to twice-daily tacrolimus (Prograf ® [Tacrolimus BID]) with the added benefit of once-daily dosing. Methods: Adult participants from four phase II de novo (kidney, liver) or Tacrolimus BID to QD conversion (kidney, heart) studies were enrolled into the follow-up study. Patients remained on the immunosuppressive regimen they were receiving on entry, unless medical needs required otherwise. The primary endpoint was patient and graft survival, and secondary endpoints were biopsy-confirmed acute rejection (BPAR) and safety. Results: The full analysis set comprised 240 patients. Tacrolimus mean total daily dose and whole-blood trough levels decreased over time, particularly in de novo patients. At fouryr, Kaplan-Meier estimates of patient and graft survival were over 90%. Freedom from BPAR was 90.9/92.6% and 100/87.0% in the de novo kidney/liver and conversion kidney/heart patients, respectively. There were 13 deaths, and 20% patients withdrew from the study, mainly because of adverse events. Conclusions: The efficacy and safety of Tacrolimus QD was maintained for fouryr in kidney, liver, and heart transplant recipients. Therefore, this formulation offers a convenient alternative to Tacrolimus BID. © 2010 John Wiley & Sons A/S.


Background: Cardiovascular (CV) disease belongs to the most important mortality causes worldwide. Early identification of risk factors and increased CV risk may help decrease of morbidity and mortality. An optimal age for CV risk factors screening ages of 40 in males and of 50 in females have been identified. CV risk profile of persons in these age categories has been examined by general practitioners and recorded for the purposes of this cross-sectional survey. Methods: 1812 persons, males at average age of 40 years and females at average age of 50 years, were included into the survey. In each of the examined family and personal history including pharmacological were recorded into the study protocol as well as abusus and physical activity patterns. Basic anthropometrical parameters, e.g. heart rate, blood pressure, body mass index and laboratory measures including blood lipids and glycaemia. The participating physicians recorded newly identified risk factors CV disease and determined the global CVD risk according to the SCORE charts. Percentage of those already treated for any of the main CVD risk factors and, among these, also attaining the treatment goals. The percentage of patients with a newly identified CV risk factor was calculated. We also tested the hypothesis of a relationship between positive family history of any of the followed risk factors and its risk in the examined probands using Pearson's test. Results: 961 males, average age of 42.9 ± 4.7 years, and 851 females, average age of 51.2 ± 3.6 years, were enrolled into the study. 49% of males and 31% of females were overweight and 32% men and 31% of women were obese. There were 36% of smokers among men and 22% among women. The prevalence of type 2 diabetes was 11% in males and also in females. Arterial hypertension was diagnosed in 43% of males and 45% of females while dyslipidemia was present in 39% of males and 41% of females. Pharmacological treatment of any of the above mentioned diseases was used in 48% of the probands, however, only 7% of them attained treatment goals of blood pressure, LDL-cholesterol and glycaemia. Type 2 diabetes was newly identified in 3% of both males and females, arterial hypertension in 8% of males and 5% of females and dyslipidemia was newly detected in 20% of probands of both genders. Non-pharmacological treatment was rec-ommended to 62% of male and to 65% of female participants, respectively. Pharmacological treatment was initiated in 53% of males and 51% of females. In both genders this was mostly antihypertensive treatment with ACE inhibitors (29% of males and 24% of females) and lipid lowering therapy with a statin (29% of males, 27% females). The analysis of relationship between the positive family history of any of the followed diseases and their presence in the probands examined revealed significant increases of the risk for arterial hypertension, type 2 diabetes melli- Tus and dyslipidemia. Conclusion: The survey following CV risk profile in a cohort of 40 years old men and 50 years old women showed high prevalence of CV risk factors in these age categories in the Czech probands. The high frequency of modifiable risk factors and the need to initiate pharmacological treatment in more than one half of the examined population documents the need of early detection of risk. Genetic determination of individual major risk factors for CVD mirrored in the positive family history represents an important component of the global cardiovascular risk and must be actively detected and taken into account for the risk stratification.


Nakagawa H.,The University of Oklahoma Health Sciences Center | Kautzner J.,IKEM | Natale A.,The Texas Institute | Peichl P.,IKEM | And 6 more authors.
Circulation: Arrhythmia and Electrophysiology | Year: 2013

Background-During radiofrequency ablation, high electrode-tissue contact force (CF) is associated with increased risk of steam pop and perforation. The purpose of this study, in patients undergoing ablation of paroxysmal atrial fibrillation, was to: (1) identify factors producing high CF during left atrial (LA) and pulmonary vein mapping; (2) determine the ability of atrial potential amplitude and impedance to predict CF; and (3) explore the feasibility of controlling radiofrequency power based on CF. Methods and Results-A high-density map of LA/pulmonary veins (median 328 sites) was obtained in 18 patients undergoing atrial fibrillation ablation using a 7.5-Fr irrigated mapping/ablation catheter to measure CF. Average CF was displayed on the 3D map. For 5682 mapped sites, CF ranged 1-144 g (median 8.2 g). High CF (≥35 g) was observed at only 118/5682 (2%) sites, clustering in 6 LA regions. The most common high CF site (48/113 sites in 17/18 patients) was located at the anterior/rightward LA roof, directly beneath the ascending aorta (confirmed by merging the CT image and map). Poor relationship between CF and either unipolar amplitude, bipolar amplitude, or impedance was observed. During ablation, radiofrequency power was modulated based on CF. All pulmonary veins were isolated without steam pop, impedance rise, or pericardial effusion. Conclusions-High CF often occurs at anterior/rightward roof, where the ascending aorta provides resistance to the LA. Atrial potential amplitude and impedance are poor predictors of CF. Controlling radiofrequency power based on CF seems to prevent steam pop and impedance rise without loss of lesion effectiveness. © 2013 American Heart Association, Inc.


Slavcev A.,IKEM
International Journal of Immunogenetics | Year: 2013

The application of solid-phase assays for detection and definition of Human leucocyte antigen (HLA)-specific antibodies has significantly facilitated the diagnosis and monitoring of treatment of antibody-mediated rejection (AMR). There is, however, a major discussion in the literature concerning the clinical relevance of the use of the Luminex technique for the prediction of cellular and/or AMR and survival. This may be explained on one hand by the complexities of the method and on the other by variations in patient demographic characteristics, immunosuppression and other factors. As far as non-HLA antibodies, it is clear that they may induce AMR; nevertheless, a difficult problem in their definition remains the fact that most of the non-HLA antigens still remain to be identified. Hereby is a short literature review of several recent publications discussing the role of HLA- and non-HLA-specific antibodies in organ transplant rejection and survival. © 2012 Blackwell Publishing Ltd.

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