Atrioventricular septal defect : advanced imaging from early development to long-term follow-up

The aim of this thesis is to review the current knowledge on atrioventricular septal defect (AVSD) (Part 1), to study the pathogenesis of AVSD (Part 2) and finally to analyze cardiac outcome long-term after AVSD correction (Part 3). Studies are performed with novel imaging techniques. In part 2 it is made plausible that AVSD is a sliding scale and that patients with Down syndrome without AVSD also have abnormalities of the membranous septum and atrioventricular valves. High frequency ultrasound in mouse embryos shows to be a promising technique to study cardiovascular flow in early stages of heart development. In a mouse model with disturbed VEGF signalling, the heart rate is reduced and the sinoatrial node develops abnormally. Finally, in part 3 of this thesis, 4DFlow MRI data reveals that patients with an abnormal left atrioventricular valve (LAVV) after AVSD correction have aberrant intra-cardiac flow patterns. During diastole the inflow into the left ventricle is directed more towards the lateral wall, more towards the apex and vortex formation is abnormal. During systole the dynamic and eccentric regurgitation of the LAVV disturbs the normal recirculating flow patterns in the left atrium.4DFlow MRI can be used to reliably quantify flow over the LAVV.UBL - phd migration 201

Echocardiographic Assessment of Embryonic and Fetal Mouse Heart Development: A Focus on Haemodynamics and Morphology

Background. Heart development is a complex process, and abnormal development may result in congenital heart disease (CHD). Currently, studies on animal models mainly focus on cardiac morphology and the availability of hemodynamic data, especially of the right heart half, is limited. Here we aimed to assess the morphological and hemodynamic parameters of normal developing mouse embryos/fetuses by using a high-frequency ultrasound system. Methods. A timed breeding program was initiated with a WT mouse line (Swiss/129Sv background). All recordings were performed transabdominally, in isoflurane sedated pregnant mice, in hearts of sequential developmental stages: 12.5, 14.5, and 17.5 days after conception (n=105). Results. Along development the heart rate increased significantly from 125 ± 9.5 to 219 ± 8.3 beats per minute. Reliable flow measurements could be performed across the developing mitral and tricuspid valves and outflow tract. M-mode measurements could be obtained of all cardiac compartments. An overall increase of cardiac systolic and diastolic function with embryonic/fetal development was observed. Conclusion. High-frequency echocardiography is a promising and useful imaging modality for structural and hemodynamic analysis of embryonic/fetal mouse hearts

Atrioventricular septal defect : advanced imaging from early development to long-term follow-up

The aim of this thesis is to review the current knowledge on atrioventricular septal defect (AVSD) (Part 1), to study the pathogenesis of AVSD (Part 2) and finally to analyze cardiac outcome long-term after AVSD correction (Part 3). Studies are performed with novel imaging techniques. In part 2 it is made plausible that AVSD is a sliding scale and that patients with Down syndrome without AVSD also have abnormalities of the membranous septum and atrioventricular valves. High frequency ultrasound in mouse embryos shows to be a promising technique to study cardiovascular flow in early stages of heart development. In a mouse model with disturbed VEGF signalling, the heart rate is reduced and the sinoatrial node develops abnormally. Finally, in part 3 of this thesis, 4DFlow MRI data reveals that patients with an abnormal left atrioventricular valve (LAVV) after AVSD correction have aberrant intra-cardiac flow patterns. During diastole the inflow into the left ventricle is directed more towards the lateral wall, more towards the apex and vortex formation is abnormal. During systole the dynamic and eccentric regurgitation of the LAVV disturbs the normal recirculating flow patterns in the left atrium.4DFlow MRI can be used to reliably quantify flow over the LAVV

Altered ascending aortic wall shear stress in patients with corrected atrioventricular septal defect: A comprehensive cardiovascular magnetic resonance and 4D flow MRI evaluation

Aim: In patients after atrioventricular septal defect correction, altered geometry leads to a changed position and subsequent flow over the left ventricular outflow tract. We hypothesised that this altered flow may influence haemodynamics in the ascending aorta.Methods: In total, 30 patients after atrioventricular septal defect correction (age 27.6 ± 12.8 years) and 28 healthy volunteers (age 24.8 ± 13.7 years) underwent 4D flow cardiovascular magnetic resonance. Left ventricular ejection fraction and mean and peak wall shear stress calculated at ascending aortic peak systole were obtained from cardiovascular magnetic resonance. Left ventricular outflow tract data including velocity and diameter were obtained from echocardiography.Results: Patients showed a higher mean (911 ± 173 versus 703 ± 154 mPa, p = 0.001) and peak ascending aortic wall shear stress (1264 ± 302 versus 1009 ± 240 mPa, p = 0.001) compared to healthy volunteers. Increased blood flow velocities over the left ventricular outflow tract (1.49 ± 0.30 m/s versus 1.22 ± 0.20 m/s, p < 0.001) correlated well with mean and peak ascending aortic wall shear stress (r = 0.67, p < 0.001 and r = 0.77, p < 0.001).Conclusion: After atrioventricular septal defect correction, increased wall shear stress was observed, which correlated to velocities over the left ventricular outflow tract. These findings imply that altered outflow tract geometry contributes to changed aortic haemodynamics

Altered ascending aortic wall shear stress in patients with corrected atrioventricular septal defect: A comprehensive cardiovascular magnetic resonance and 4D flow MRI evaluation

Aim:In patients after atrioventricular septal defect correction, altered geometry leads to a changed position and subsequent flow over the left ventricular outflow tract. We hypothesised that this altered flow may influence haemodynamics in the ascending aorta.Methods:In total, 30 patients after atrioventricular septal defect correction (age 27.6 ± 12.8 years) and 28 healthy volunteers (age 24.8 ± 13.7 years) underwent 4D flow cardiovascular magnetic resonance. Left ventricular ejection fraction and mean and peak wall shear stress calculated at ascending aortic peak systole were obtained from cardiovascular magnetic resonance. Left ventricular outflow tract data including velocity and diameter were obtained from echocardiography.Results:Patients showed a higher mean (911 ± 173 versus 703 ± 154 mPa, p = 0.001) and peak ascending aortic wall shear stress (1264 ± 302 versus 1009 ± 240 mPa, p = 0.001) compared to healthy volunteers. Increased blood flow velocities over the left ventricular outflow tract (1.49 ± 0.30 m/s versus 1.22 ± 0.20 m/s, p < 0.001) correlated well with mean and peak ascending aortic wall shear stress (r = 0.67, p < 0.001 and r = 0.77, p < 0.001).Conclusion:After atrioventricular septal defect correction, increased wall shear stress was observed, which correlated to velocities over the left ventricular outflow tract. These findings imply that altered outflow tract geometry contributes to changed aortic haemodynamics