Utrecht, Netherlands
Utrecht, Netherlands

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van der Bom T.,The Netherlands Heart Institute | Pieper P.G.,University of Groningen | van Dijk A.P.J.,Radboud University Nijmegen | Helbing W.A.,Erasmus MC Sophia Childrens Hospital | And 2 more authors.
Congenital Heart Disease | Year: 2015

Objective: To evaluate differences in functional parameters and reproducibility between short axis and axial slice orientation in the quantitative evaluation of the systemic right ventricle by cardiovascular magnetic resonance. Design: Cross-sectional evaluation comparing two methods (Bland-Altman). Setting: Tertiary care outpatients. Interventions: Quantitative cardiovascular magnetic resonance evaluation using short axis or axial slice orientation. Main Outcome Measures: Intraobserver variance, interobserver variance and systematic differences in systemic right ventricular volumes, ejection fraction, and mass between both methods. Patients: Twenty-two patients (mean age 33 ± 7 years) with systemic right ventricle (three with congenitally corrected transposition of the great arteries and 19 with atrially switched transposition of the great arteries). Results: Compared with short axis slices, analysis of axial slices resulted in higher end systolic volume (6.6%, P < .01), while mass (-10.8%, P < .01) and ejection fraction (-8.9%, P < .01) turned out lower. Intraobserver and interobserver reproducibility were similar for both methods when measuring end-diastolic and end-systolic volumes. However, ejection fraction and stroke volume were measured more consistently in axial orientation, while ventricular mass was measured more consistently in short axis orientation. Conclusion: There are significant differences in volume, mass, and function between measurements in axial and short axis orientation. Ejection fraction and stroke volume, which have a high clinical relevance, were measured more consistently in axial slice orientation. Consequently, we recommend using axial slice orientation in patients with a systemic right ventricle. © 2014 Wiley Periodicals, Inc.


Arslan F.,University Utrecht | Arslan F.,The Netherlands Heart Institute | Smeets M.B.,The Netherlands Heart Institute | Buttari B.,Instituto Superiore Of Sanita | And 14 more authors.
Journal of Molecular and Cellular Cardiology | Year: 2013

Decreased haptoglobin (Hp) functionality due to allelic variations is associated with worsened outcome in patients after myocardial infarction (MI). However, mechanisms through which haptoglobin deficiency impairs cardiac repair remain to be elucidated. In the present study, we identified novel molecular alterations mediated by Hp involved in early and late cardiac repair responses after left coronary artery ligation in Hp-/- and wild-type (WT) mice. We observed a higher mortality rate in Hp-/- mice despite similar infarct size between groups. Deaths were commonly caused by cardiac rupture in Hp-/- animals. Histological analysis of 3 and 7days old non-ruptured infarcted hearts revealed more frequent and more severe intramural hemorrhage and increased leukocyte infiltration in Hp-/- mice. Analyses of non-ruptured hearts revealed increased oxidative stress, reduced PAI-1 activity and enhanced VEGFα transcription in Hp-/- mice. In line with these observations, we found increased microvascular permeability in Hp-/- hearts 3days after infarction. In vitro, haptoglobin prevented hemoglobin-induced oxidative stress and restored VEGF/Ang-1 balance in endothelial cell cultures. During long-term follow-up of the surviving animals, we observed altered matrix turnover, impaired scar formation and worsened cardiac function and geometry in Hp-/-mice. In conclusion, haptoglobin deficiency severely deteriorates tissue repair and cardiac performance after experimental MI. Haptoglobin plays a crucial role in both short- and long-term cardiac repair responses by reducing oxidative stress, maintaining microvascular integrity, myocardial architecture and proper scar formation. © 2012 Elsevier Ltd.


Rain S.,VU University Amsterdam | Goncalves Bos D.S.,VU University Amsterdam | Handoko M.L.,VU University Amsterdam | Westerhof N.,VU University Amsterdam | And 20 more authors.
Journal of the American Heart Association | Year: 2014

Background-Right ventricular (RV) diastolic function is impaired in patients with pulmonary arterial hypertension (PAH). Our previous study showed that elevated cardiomyocyte stiffness and myofilament Ca2+ sensitivity underlie diastolic dysfunction in PAH. This study investigates protein modifications contributing to cellular diastolic dysfunction in PAH. Methods and Results-RV samples from PAH patients undergoing heart-lung transplantation were compared to non-failing donors (Don). Titin stiffness contribution to RV diastolic dysfunction was determined by Western-blot analyses using antibodies to proteinkinase- A (PKA), Cα (PKCα) and Ca2+/calmoduling-dependent-kinase (CamKIIδ) titin and phospholamban (PLN) phosphorylation sites: N2B (Ser469), PEVK (Ser170 and Ser26), and PLN (Thr17), respectively. PKA and PKCα sites were significantly less phosphorylated in PAH compared with donors (P < 0.0001). To test the functional relevance of PKA-, PKCα-, and CamKIIδ-mediated titin phosphorylation, we measured the stiffness of single RV cardiomyocytes before and after kinase incubation. PKA significantly decreased PAH RV cardiomyocyte diastolic stiffness, PKCα further increased stiffness while CamKIIδ had no major effect. CamKIId activation was determined indirectly by measuring PLN Thr 17phosphorylation level. No significant changes were found between the groups. Myofilament Ca2+ sensitivity is mediated by sarcomeric troponin/(cTnI) phosphorylation. We observed increased unphosphorylated cTnI in PAH compared with donors (P < 0.05) and reduced PKA-mediated cTnI phosphorylation (Ser22/23) (P < 0.001). Finally, alterations in Ca2+-handling proteins contribute to RV diastolic dysfunction due to insufficient diastolic Ca2+ clearance. PAH SERCA2a levels and PLN phosphorylation were significantly reduced compared with donors (P < 0.05). Conclusions-Increased titin stiffness, reduced cTnI phosphorylation, and altered levels of phosphorylation of Ca2+ handling proteins contribute to RV diastolic dysfunction in PAH. © 2014 The Authors.


PubMed | The Netherlands Heart Institute
Type: Comparative Study | Journal: Congenital heart disease | Year: 2015

To evaluate differences in functional parameters and reproducibility between short axis and axial slice orientation in the quantitative evaluation of the systemic right ventricle by cardiovascular magnetic resonance.Cross-sectional evaluation comparing two methods (Bland-Altman).Tertiary care outpatients.Quantitative cardiovascular magnetic resonance evaluation using short axis or axial slice orientation.Intraobserver variance, interobserver variance and systematic differences in systemic right ventricular volumes, ejection fraction, and mass between both methods.Twenty-two patients (mean age 33 7 years) with systemic right ventricle (three with congenitally corrected transposition of the great arteries and 19 with atrially switched transposition of the great arteries).Compared with short axis slices, analysis of axial slices resulted in higher end systolic volume (6.6%, P < .01), while mass (-10.8%, P < .01) and ejection fraction (-8.9%, P < .01) turned out lower. Intraobserver and interobserver reproducibility were similar for both methods when measuring end-diastolic and end-systolic volumes. However, ejection fraction and stroke volume were measured more consistently in axial orientation, while ventricular mass was measured more consistently in short axis orientation.There are significant differences in volume, mass, and function between measurements in axial and short axis orientation. Ejection fraction and stroke volume, which have a high clinical relevance, were measured more consistently in axial slice orientation. Consequently, we recommend using axial slice orientation in patients with a systemic right ventricle.

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