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van der Schaaf R.J.,University of Amsterdam | Claessen B.E.,University of Amsterdam | Hoebers L.P.,University of Amsterdam | Verouden N.J.,University of Amsterdam | And 12 more authors.

Background: In the setting of primary percutaneous coronary intervention, patients with a chronic total occlusion in a non-infarct related artery were recently identified as a high-risk subgroup. It is unclear whether ST-elevation myocardial infarction patients with a chronic total occlusion in a non-infarct related artery should undergo additional percutaneous coronary intervention of the chronic total occlusion on top of optimal medical therapy shortly after primary percutaneous coronary intervention. Possible beneficial effects include reduction in adverse left ventricular remodeling and preservation of global left ventricular function and improved clinical outcome during future coronary events.Methods/Design: The Evaluating Xience V and left ventricular function in Percutaneous coronary intervention on occLusiOns afteR ST-Elevation myocardial infarction (EXPLORE) trial is a randomized, prospective, multicenter, two-arm trial with blinded evaluation of endpoints. Three hundred patients after primary percutaneous coronary intervention for ST-elevation myocardial infarction with a chronic total occlusion in a non-infarct related artery are randomized to either elective percutaneous coronary intervention of the chronic total occlusion within seven days or standard medical treatment. When assigned to the invasive arm, an everolimus-eluting coronary stent is used. Primary endpoints are left ventricular ejection fraction and left ventricular end-diastolic volume assessed by cardiac Magnetic Resonance Imaging at four months. Clinical follow-up will continue until five years.Discussion: The ongoing EXPLORE trial is the first randomized clinical trial powered to investigate whether recanalization of a chronic total occlusion in a non-infarct related artery after primary percutaneous coronary intervention for ST-elevation myocardial infarction results in a better preserved residual left ventricular ejection fraction, reduced end-diastolic volume and enhanced clinical outcome.Trial registration: trialregister.nl NTR1108. © 2010 van der Schaaf et al; licensee BioMed Central Ltd. Source

Vanderheyden M.,Onze Lieve Vrouwe Ziekenhuis | Vrints C.,University of Antwerp | Verstreken S.,Onze Lieve Vrouwe Ziekenhuis | Bartunek J.,Onze Lieve Vrouwe Ziekenhuis | And 2 more authors.
Biomarkers in Medicine

The mature, biologically active 32-amino acid long B-type natriuretic peptide (BNP1-32), is cleaved by corin from the BNP prohormone. Recent data demonstrated that BNP1-32 might be an ideal substrate for the endogenous aminopeptidase, dipeptidyl-peptidase (DPP) IV. DPP IV removes the two amino-terminal amino acids (Ser and Pro) from BNP1-32 to produce BNP3-32, which has been detected in plasma of patients with heart failure. In a canine model, intravenous BNP3-32 infusion resulted in less natriuresis, diuresis and vasodilation compared to intravenous infusion of BNP1-32. The clinical relevance of these observations may be important for patients with high plasma BNP concentrations, which can be measured by commercially available immunoassays. Further studies are needed to explore whether DPP IV inhibitors increase the bioavailability of BNP 1-32, delay the progression of heart failure and increase the efficacy of exogenously administered BNP1-32 in decompensated heart failure. © 2010 Future Medicine Ltd. Source

Vanderheyden M.,Onze Lieve Vrouwe Ziekenhuis | Houben R.,Medtronic | Verstreken S.,Onze Lieve Vrouwe Ziekenhuis | Stahlberg M.,Karolinska Hospital Solna Stockholm | And 3 more authors.
Circulation: Heart Failure

Background: Hemodynamic monitoring using implantable devices may provide early warning of volume overload in patients with heart failure (HF). This study was designed to prospectively compare information from intrathoracic impedance monitoring and continuous right ventricular pressure measurements in patients with HF. Methods and Results: Sixteen patients with HF (age, 63.5±13.8 years; left ventricular ejection fraction, 23.2±11.3%; New York Heart Association, II and III) and a previous HF decompensation received both a cardiac resynchronization therapy defibrillator providing a daily average of intrathoracic impedance and an implantable hemodynamic monitor providing an estimate of the pulmonary artery diastolic pressure. At the end of a 6-month investigator-blinded period, baseline reference hemodynamic values were determined over 4 weeks during which the patient was clinically stable. A major HF event was defined as HF decompensation requiring hospitalization, IV diuretic treatment, or leading to death. Sixteen major HF events occurred in 10 patients. Within 30 days and 14 days before a major HF event, impedance decreased by 0.12±0.21 Ω/d and 0.20±0.20 Ω/d, respectively, whereas estimated pulmonary arterial diastolic pressure increased by 0.10±0.20 mm Hg/d and 0.16±0.15 mm Hg/d, respectively. During these periods, impedance decreased by 3.8±5.4 Ω (P<0.02) and 4.9±6.1 Ω (P<0.007), respectively, whereas estimated pulmonary arterial diastolic pressure increased by 5.8±5.7 mm Hg (P<0.002) and 6.8±6.1 mm Hg (P<0.001), respectively, compared with baseline. In all patients, impedance and estimated pulmonary arterial diastolic pressure were inversely correlated (r=-0.48±0.25). Within 30 days preceding a major HF event, this correlation improved to r=-0.58±0.24. Conclusions: Decompensated HF develops based on hemodynamic derangements and is preceded by significant changes in intrathoracic impedance and right ventricular pressures during the month prior to a major clinical event. Impedance and pressure changes are moderately correlated. Future research may establish the complementary contribution of both parameters to guide diagnosis and management of patients with HF by implantable devices. © 2010 American Heart Association, Inc. Source

Van Haelst I.M.M.,Medical Center Alkmaar | Van Haelst I.M.M.,University Utrecht | Van Klei W.A.,University Utrecht | Doodeman H.J.,Medical Center Alkmaar | And 21 more authors.
Journal of Clinical Psychiatry

Objective: To investigate the occurrence of intraoperative hemodynamic events when antidepressive treatment with monoamine oxidase inhibitors (MAOIs) was continued during anesthesia. Method: A retrospective observational cohort study was conducted among patients who were admitted for elective surgery requiring anesthesia in 8 Dutch hospitals (2004-2010). The index group included current users of irreversible (tranylcypromine) and reversible (moclobemide) MAOIs. The reference group included a sample of nonusers matched to the index group on hospital, type and period of surgery, and type of anesthesia (ratio 1:3). The outcome of interest was the occurrence of the following intraoperative hemodynamic events: hypotension or hypertension and tachycardia or bradycardia. Results: Approximately 280,000 surgical procedures were performed in the participating hospitals in the total observational period of 33 years. The index group included 26 and 25 users of tranylcypromine and moclobemide, respectively. The reference groups included 149 nonusers. Intraoperative hypotension occurred less frequently in users of tranylcypromine (46%) than in nonusers (73%) (P = .01). The occurrence of hypertension, bradycardia, and tachycardia during anesthesia was not different between users of tranylcypromine (27%, 50%, and 12%, respectively) and those in the reference group (35%, 61%, and 26%, respectively). The occurrence of hypotension, hypertension, bradycardia, and tachycardia was not different between users of moclobemide and the reference group. Conclusions: Severe adverse hemodynamic events, such as hypertension and tachycardia, did not occur more frequently in users of both the irreversible MAOI tranylcypromine and the reversible MAO-A inhibitor moclobemide compared to nonusers. These findings suggest that there is no longer much justification to discontinue these MAOIs before surgery, with the considerable risk of compromising patients' psychiatric status. © Copyright 2012 Physicians Postgraduate Press, Inc. Source

Beunders G.,VU University Amsterdam | Voorhoeve E.,VU University Amsterdam | Golzio C.,Duke University | Pardo L.M.,VU University Amsterdam | And 74 more authors.
American Journal of Human Genetics

Genomic rearrangements involving AUTS2 (7q11.22) are associated with autism and intellectual disability (ID), although evidence for causality is limited. By combining the results of diagnostic testing of 49,684 individuals, we identified 24 microdeletions that affect at least one exon of AUTS2, as well as one translocation and one inversion each with a breakpoint within the AUTS2 locus. Comparison of 17 well-characterized individuals enabled identification of a variable syndromic phenotype including ID, autism, short stature, microcephaly, cerebral palsy, and facial dysmorphisms. The dysmorphic features were more pronounced in persons with 3′ AUTS2 deletions. This part of the gene is shown to encode a C-terminal isoform (with an alternative transcription start site) expressed in the human brain. Consistent with our genetic data, suppression of auts2 in zebrafish embryos caused microcephaly that could be rescued by either the full-length or the C-terminal isoform of AUTS2. Our observations demonstrate a causal role of AUTS2 in neurocognitive disorders, establish a hitherto unappreciated syndromic phenotype at this locus, and show how transcriptional complexity can underpin human pathology. The zebrafish model provides a valuable tool for investigating the etiology of AUTS2 syndrome and facilitating gene-function analysis in the future. © 2013 The American Society of Human Genetics. Source

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