Nieuwegein, Netherlands
Nieuwegein, Netherlands

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Liebregts M.,St Antonius Hospital Nieuwegein | Steggerda R.C.,Martini Hospital | Vriesendorp P.A.,Erasmus Medical Center | Van Velzen H.,Erasmus Medical Center | And 6 more authors.
JACC: Cardiovascular Interventions | Year: 2016

Objectives The aim of this study was to compare outcomes of alcohol septal ablation (ASA) in young and elderly patients with obstructive hypertrophic cardiomyopathy (HCM). Background The American College of Cardiology Foundation/American Heart Association guidelines reserve ASA for elderly patients and patients with serious comorbidities. Information on long-term age-specific outcomes after ASA is scarce. Methods This cohort study included 217 HCM patients (age 54 ± 12 years) who underwent ASA because of symptomatic left ventricular outflow tract obstruction. Patients were divided into young (age ≤55 years) and elderly (age >55 years) groups and matched by age in a 1:1 fashion to nonobstructive HCM patients. Results Atrioventricular block following ASA was more common in elderly patients (43% vs. 21%; p = 0.001), resulting in pacemaker implantation in 13% and 5%, respectively (p = 0.06). Residual left ventricular outflow tract gradient, post-procedural New York Heart Association functional class, and necessity for additional septal reduction therapy was comparable between age groups. During a follow-up of 7.6 ± 4.6 years, 54 patients died. The 5- and 10-year survival following ASA was 95% and 90% in patients age ≤55 years and 93% and 82% in patients age >55 years, which was comparable to their control groups. The annual adverse arrhythmic event rate following ASA was 0.7%/year in young patients and 1.4%/year in elderly patients, which was comparable to their control groups. Conclusions ASA is similarly effective for reduction of symptoms in young and elderly patients; however, younger patients have a lower risk of procedure-related atrioventricular conduction disturbances. The long-term mortality rate and risk of adverse arrhythmic events following ASA are low, both in young and elderly patients, and are comparable to age-matched nonobstructive HCM patients. © 2016 American College of Cardiology Foundation.


Tantry U.S.,Sinai Hospital of Baltimore | Bonello L.,Aix - Marseille University | Aradi D.,Heart Center Balatonfured | Price M.J.,Scripps Research Institute | And 19 more authors.
Journal of the American College of Cardiology | Year: 2013

Dual antiplatelet therapy with aspirin and a P2Y12 receptor blocker is a key strategy to reduce platelet reactivity and to prevent thrombotic events in patients treated with percutaneous coronary intervention. In an earlier consensus document, we proposed cutoff values for high on-treatment platelet reactivity to adenosine diphosphate (ADP) associated with post-percutaneous coronary intervention ischemic events for various platelet function tests (PFTs). Updated American and European practice guidelines have issued a Class IIb recommendation for PFT to facilitate the choice of P2Y 12 receptor inhibitor in selected high-risk patients treated with percutaneous coronary intervention, although routine testing is not recommended (Class III). Accumulated data from large studies underscore the importance of high on-treatment platelet reactivity to ADP as a prognostic risk factor. Recent prospective randomized trials of PFT did not demonstrate clinical benefit, thus questioning whether treatment modification based on the results of current PFT platforms can actually influence outcomes. However, there are major limitations associated with these randomized trials. In addition, recent data suggest that low on-treatment platelet reactivity to ADP is associated with a higher risk of bleeding. Therefore, a therapeutic window concept has been proposed for P2Y 12 inhibitor therapy. In this updated consensus document, we review the available evidence addressing the relation of platelet reactivity to thrombotic and bleeding events. In addition, we propose cutoff values for high and low on-treatment platelet reactivity to ADP that might be used in future investigations of personalized antiplatelet therapy. © 2013 by the American College of Cardiology Foundation.


Te Riele W.W.,St Antonius Hospital Nieuwegein | Boerma D.,Onze Lieve Vrouwe Gasthuis | Wiezer M.J.,St Antonius Hospital Nieuwegein | Rinkes I.H.M.B.,University Utrecht | Van Ramshorst B.,St Antonius Hospital Nieuwegein
British Journal of Surgery | Year: 2010

Background: The aim of the study was to evaluate the results of laparoscopic adjustable gastric banding (LAGB) in patients lost to follow-up. Methods: Patients lost to follow-up were identified from a consecutive cohort of 495 patients who underwent LAGB between November 1995 and September 2006. These patients were asked to return to follow-up and their actual weight was assessed. Results: Of 93 patients lost to follow-up, 73 were motivated to reattend. Of these, 60 per cent (44 patients) had lost less than 25 per cent of excess weight, compared with 16·3 per cent (P < 0·001), 27·0 per cent (P < 0·001) and 42 per cent (P = 0·026) of patients after 2, 4 and 8 years of regular follow-up. Conclusion: Patients lost to follow-up are more likely to have poor weight loss, emphasizing the importance of follow-up after LAGB. Outcome after surgery for morbid obesity should include patients lost to follow-up as a measure of overall success. © 2010 British Journal of Surgery Society Ltd.


Rutten J.M.T.M.,Emma Childrens Hospital Academic Medical Center | Reitsma J.B.,University Utrecht | Vlieger A.M.,St Antonius Hospital Nieuwegein | Benninga M.A.,Emma Childrens Hospital Academic Medical Center
Archives of Disease in Childhood | Year: 2013

Objectives: Gut directed hypnotherapy (HT) is shown to be effective in adult functional abdominal pain (FAP) and irritable bowel syndrome (IBS) patients. We performed a systematic review to assess efficacy of HT in paediatric FAP/IBS patients. Methods: We searched Medline, Embase, PsychINFO, Cumulative Index to Nursing and Allied Health Literature databases and Cochrane Central Register of Controlled Trials for randomised controlled trials (RCT) in children with FAP or IBS, investigating efficacy of HT on the following outcomes: abdominal pain scores, quality of life, costs and school absenteeism. Results: Three RCT comparing HT to a control treatment were included with sample sizes ranging from 22 to 52 children. We refrained from statistical pooling because of low number of studies and many differences in design and outcomes. Two studies examined HT performed by a therapist, one examined HT through selfexercises on audio CD. All trials showed statistically significantly greater improvement in abdominal pain scores among children receiving HT. One trial reported beneficial effects sustained after 1 year of follow-up. One trial reported statistically significant improvement in quality of life in the HT group. Two trials reported significant reductions in school absenteeism after HT. Conclusions: Therapeutic effects of HT seem superior to standard medical care in children with FAP or IBS. It remains difficult to quantify exact benefits. The need for more high quality research is evident.


Janssen P.W.A.,St Antonius Hospital Nieuwegein | Ten Berg J.M.,St Antonius Hospital Nieuwegein
Journal of Cardiovascular Translational Research | Year: 2013

Dual antiplatelet therapy, consisting of aspirin and a P2Y12 receptor inhibitor, has dramatically reduced the incidence of atherothrombotic events for patients with acute coronary syndrome and those undergoing a percutaneous coronary intervention (PCI). However, the platelet inhibitory effect of clopidogrel, the most commonly used P2Y12 inhibitor, is variable between patients. Patients exhibiting high platelet reactivity (HPR) despite clopidogrel treatment are at higher risk of recurrent atherothrombotic events after PCI. In order to reduce the incidence of HPR, the more potent P2Y12 receptor inhibitors prasugrel and ticagrelor are used. However, these drugs increase the risk of bleeding. As there is evidence of a therapeutic window for platelet inhibition, platelet function tests could be helpful for tailoring antiplatelet therapy based on the patient's thrombotic and bleeding risk. In the present article, we review the most commonly used platelet function tests and the current evidence for tailoring of antiplatelet therapy in PCI patients. © 2013 Springer Science+Business Media New York.


Vriesendorp P.A.,Erasmus University Rotterdam | Schinkel A.F.L.,Erasmus University Rotterdam | Liebregts M.,St Antonius Hospital Nieuwegein | Theuns D.A.M.J.,Erasmus University Rotterdam | And 4 more authors.
Circulation: Arrhythmia and Electrophysiology | Year: 2015

Background - The recently released 2014 European Society of Cardiology guidelines of hypertrophic cardiomyopathy (HCM) use a new clinical risk prediction model for sudden cardiac death (SCD), based on the HCM Risk-SCD study. Our study is the first external and independent validation of this new risk prediction model. Methods and Results - The study population consisted of a consecutive cohort of 706 patients with HCM without prior SCD event, from 2 tertiary referral centers. The primary end point was a composite of SCD and appropriate implantable cardioverter-defibrillator therapy, identical to the HCM Risk-SCD end point. The 5-year SCD risk was calculated using the HCM Risk-SCD formula. Receiver operating characteristic curves and C-statistics were calculated for the 2014 European Society of Cardiology guidelines, and risk stratification methods of the 2003 American College of Cardiology/European Society of Cardiology guidelines and 2011 American College of Cardiology Foundation/American Heart Association guidelines. During follow-up of 7.7±5.3 years, SCD occurred in 42 (5.9%) of 706 patients (ages 49±16 years; 34% women). The C-statistic of the new model was 0.69 (95% CI, 0.57-0.82; P=0.008), which performed significantly better than the conventional risk factor models based on the 2003 guidelines (C-statistic of 0.55: 95% CI, 0.47-0.63; P=0.3), and 2011 guidelines (C-statistic of 0.60: 95% CI, 0.50-0.70; P=0.07). Conclusions - The HCM Risk-SCD model improves the risk stratification of patients with HCM for primary prevention of SCD, and calculating an individual risk estimate contributes to the clinical decision-making process. Improved risk stratification is important for the decision making before implantable cardioverter-defibrillator implantation for the primary prevention of SCD. © 2015 American Heart Association, Inc.


Bouman H.J.,St Antonius Hospital Nieuwegein | Bouman H.J.,Maastricht University | Schomig E.,University of Cologne | Van Werkum J.W.,St Antonius Hospital Nieuwegein | And 7 more authors.
Nature Medicine | Year: 2011

Clinical efficacy of the antiplatelet drug clopidogrel is hampered by its variable biotransformation into the active metabolite. The variability in the clinical response to clopidogrel treatment has been attributed to genetic factors, but the specific genes and mechanisms underlying clopidogrel bioactivation remain unclear. Using in vitro metabolomic profiling techniques, we identified paraoxonase-1 (PON1) as the crucial enzyme for clopidogrel bioactivation, with its common Q192R polymorphism determining the rate of active metabolite formation. We tested the clinical relevance of the PON1 Q192R genotype in a population of individuals with coronary artery disease who underwent stent implantation and received clopidogrel therapy. PON1 QQ192 homozygous individuals showed a considerably higher risk than RR192 homozygous individuals of stent thrombosis, lower PON1 plasma activity, lower plasma concentrations of active metabolite and lower platelet inhibition. Thus, we identified PON1 as a key factor for the bioactivation and clinical activity of clopidogrel. These findings have therapeutic implications and may be exploited to prospectively assess the clinical efficacy of clopidogrel. © 2011 Nature America, Inc. All rights reserved.


Verschuur-Maes A.H.J.,University Utrecht | De Bruin P.C.,St Antonius Hospital Nieuwegein | Van Diest P.J.,University Utrecht
Breast Cancer Research and Treatment | Year: 2012

Promoter hypermethylation of several tumour suppressor genes often occurs during breast carcinogenesis, but little is known about epigenetic silencing in the possible precursor columnar cell lesion (CCL). Promoter hypermethylation of 50 different tumour suppressor genes was assessed in normal breast tissue (N = 10), CCL (N = 15), ductal carcinoma in situ (DCIS) grade I originating in CCL (N = 5) and paired CCL (N = 15) with DCIS (N = 7) and/or invasive carcinoma (N = 14) by Methylation-specific multiplex ligation-dependent probe amplification. Increasing mean cumulative methylation levels were found from normal breast tissue to CCL to DCIS and invasive carcinoma (P < 0.001) with similar methylation levels in DCIS and invasive carcinoma. Methylation levels and frequencies (in the overall analysis and analysis of only the synchronous lesions) were the highest for RASSF1, CCND2, ID4, SCGB3A1 and CDH13. The methylation levels of ID4, CCND2, and CDH13 increased significantly from normal breast tissue to CCL and to DCIS/invasive carcinoma. RASSF1, SCGB3A1 and SFRP5 had significant higher methylation levels in CCL compared to normal breast tissue, but showed no significant differences between CCL, DCIS and invasive carcinoma. Also, no difference was found between CCLs with and without atypia, or CCLs with or without synchronous cancer. In conclusion, promoter hypermethylation for several established tumour suppressor genes is already present in CCLs, underlining that promoter hypermethylation is an early event in breast carcinogenesis. Atypia in CCL or the presence of synchronous more advanced lesions does not seem to be accompanied by higher methylation levels. © 2012 Springer Science+Business Media New York.


Rutten J.M.T.M.,Emma Childrens Hospital | Benninga M.A.,Emma Childrens Hospital | Vlieger A.M.,St Antonius Hospital Nieuwegein
Journal of Pediatric Gastroenterology and Nutrition | Year: 2014

Conclusions: Pediatric patients with IBS and those with FAPS have similar psychosocial profiles. These results may explain why treatment response of psychological therapies in these AP-FGIDs is similar. These results may indicate that pediatric IBS and FAPS are different expressions of 1 underlying functional disorder, but similarities in psychosocial characteristics do not exclude the possibility that these disorders are different entities, because these similarities can exist between disorders of various causes. Therefore, future research is required on the role of other (physiological) factors in pediatric IBS and FAPS.Methods: A total of 259 children, ages 8 to 18 years, fulfilling Rome III criteria for IBS or FAPS were included in a randomized controlled trial evaluating the effect of hypnotherapy. At inclusion, questionnaires assessed demographics, clinical features, abdominal pain frequency and intensity, depression and anxiety, somatization, health-related quality of life, pain beliefs, and coping strategies.Objectives: It has been suggested that different subcategories of childhood abdominal pain-related functional gastrointestinal disorders (AP-FGIDs) are not separate clinical entities, but represent variable expressions of the same FGID. The aimof the present study was to compare clinical and psychological characteristics of children with irritable bowel syndrome (IBS), functional abdominal pain (FAP), and functional abdominal pain syndrome (FAPS).Results: No differenceswere found between children with IBS and those with FAPS with respect to the main outcomes: frequency and intensity of abdominal pain, symptoms of depression and anxiety, somatization, healthrelated quality of life, pain beliefs, and coping strategies. Asignificantly higher percentage of patients with IBS had a positive family history for AP-FGIDs (56.8% vs 37.8%; P=0.00). Characteristics of patients with IBS subtypes did not differ. Patients with FAP or FAPS differed only with respect to problem-focused coping strategy (2.21± 0.61 vs 2.52± 0.49; P=0.00. © 2014 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.


Kropman R.H.J.,St Antonius Hospital Nieuwegein | Schrijver A.M.,St Antonius Hospital Nieuwegein | Kelder J.C.,St Antonius Hospital Nieuwegein | Moll F.L.,University Utrecht | de Vries J.P.P.M.,St Antonius Hospital Nieuwegein
European Journal of Vascular and Endovascular Surgery | Year: 2010

Objectives: A systematic review was performed to summarise outcomes of acute thrombosed popliteal artery aneurysms (PAAs) treated with thrombolysis or thrombectomy followed by bypass. Methods: A systematic review was conducted of data on acute thrombosed PAAs dated 1 January 1990 through 30 June 2008 using the Cochrane Library, MEDLINE and EMBASE databases. Primary endpoint was limb salvage; secondary endpoints were mortality and patency of the bypasses. Results: Eight prospective studies and 25 retrospective studies with 895 patients presenting with acute ischaemia were included. No randomised trials were included. The mortality rate after surgical repair was 3.2% (95% confidence interval (C.I.) 1.8-4.6). The amputation rate was 14.1% (95% C.I. 11.8-16.4). Thrombolysis before surgery did not result in a significant reduction of the number of amputations, compared with surgery (thrombectomy and bypass) alone. The mean primary patency rates of the bypasses at 1, 3 and 5 years were 79%, 77% and 74%, respectively, in the 'thrombolysis' group and 71% (P = 0.026), 54% (P = 0.164) and 45% (P = 0.249) in the 'thrombectomy' group. No distinction could be made regarding secondary patency and limb-salvage rates between the groups owing to insufficient data. Conclusions: Preoperative and intra-operative thrombolyses result in a significant improvement in 1-year primary graft patency rates, but do not result in a significant reduction for amputations compared with surgery alone. © 2009 European Society for Vascular Surgery.

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