Background: Bicuspid aortic valve (BAV) is associated with ascending aorta aneurysms and dissections. Presently, genetic factors and pathological flow patterns are considered responsible for... Show moreBackground: Bicuspid aortic valve (BAV) is associated with ascending aorta aneurysms and dissections. Presently, genetic factors and pathological flow patterns are considered responsible for aneurysm formation in BAV while the exact role of inflammatory processes remains unknown.Methods: In order to objectify inflammation, we employ a highly sensitive, quantitative immunohistochemistry approach. Whole slides of dissected, dilated and non-dilated ascending aortas from BAV patients were quantitatively analyzed.Results: Dilated aortas show a 4-fold increase of lymphocytes and a 25-fold increase in B lymphocytes in the adventitia compared to non-dilated aortas. Tertiary lymphoid structures with B cell follicles and helper T cell expansion were identified in dilated and dissected aortas. Dilated aortas were associated with an increase in M1-like macrophages in the aorta media, in contrast the number of M2-like macrophages did not change significantly.Conclusion: This study finds unexpected large numbers of immune cells in dilating aortas of BAV patients. These findings raise the question whether immune cells in BAV aortopathy are innocent bystanders or contribute to the deterioration of the aortic wall. Show less
Background:Four-dimensional flow magnetic resonance imaging (4D flow MRI) can accurately visualize and quantify flow and provide hemodynamic information such as wall shear stress (WSS). This... Show moreBackground:Four-dimensional flow magnetic resonance imaging (4D flow MRI) can accurately visualize and quantify flow and provide hemodynamic information such as wall shear stress (WSS). This imaging technique can be used to obtain more insight in the hemodynamic changes during cardiac cycle in the true and false lumen of uncomplicated acute Type B Aortic Dissection (TBAD). Gaining more insight of these forces in the false lumen in uncomplicated TBAD during optimal medical treatment, might result in prediction of adverse outcomes.Methods:A porcine aorta dissection model with an artificial dissection was positioned in a validated ex-vivo circulatory system with physiological pulsatile flow. 4D flow MR images with 3 set heartrates (HR; 60 bpm, 80 bpm and 100 bpm) were acquired. False lumen volume per cycle (FLV), mean and peak systolic WSS were determined from 4D flow MRI data. For validation, the experiment was repeated with a second porcine aorta dissection model.Results:During both experiments an increase in FLV (initial experiment: Delta FLV = 2.05 ml, p < 0.001, repeated experiment: Delta FLV = 1.08 ml, p = 0.005) and peak WSS (initial experiment: Delta WSS = 1.2 Pa, p = 0.004, repeated experiment: Delta WSS = 1.79 Pa, p = 0.016) was observed when HR increased from 60 to 80 bpm. Raising the HR from 80 to 100 bpm, no significant increase in FLV (p = 0.073, p = 0.139) was seen during both experiments. The false lumen mean WSS increased significant during initial (2.71 to 3.85 Pa; p = 0.013) and non-significant during repeated experiment (3.22 to 4.00 Pa; p = 0.320).Conclusion:4D flow MRI provides insight into hemodynamic dimensions including WSS. Our ex-vivo experiments showed that an increase in HR from 60 to 80 bpm resulted in a significant increase of FLV and WSS of the false lumen. We suggest that strict heart rate control is of major importance to reduce the mean and peak WSS in uncomplicated acute TBAD. Because of the limitations of an ex-vivo study, 4D flow MRI will have to be performed in clinical setting to determine whether this imaging model would be of value to predict the course of uncomplicated TBAD. Show less
Disease-causing variants in TGFB3 cause an autosomal dominant connective tissue disorder which is hard to phenotypically delineate because of the small number of identified cases. The purpose of... Show moreDisease-causing variants in TGFB3 cause an autosomal dominant connective tissue disorder which is hard to phenotypically delineate because of the small number of identified cases. The purpose of this retrospective cross-sectional multicenter study is to elucidate the genotype and phenotype in an international cohort of TGFB3 patients. Eleven (eight novel) TGFB3 disease-causing variants were identified in 32 patients (17 families). Aortic root dilatation and mitral valve disease represented the most common cardiovascular findings, reported in 29% and 32% of patients, respectively. Dissection involving distal aortic segments occurred in two patients at age 50 and 52 years. A high frequency of systemic features (65% high-arched palate, 63% arachnodactyly, 57% pectus deformity, 52% joint hypermobility) was observed. In familial cases, incomplete penetrance and variable clinical expressivity were noted. Our cohort included the first described homozygous patient, who presented with a more severe phenotype compared to her heterozygous relatives. In conclusion, TGFB3 variants were associated with a high percentage of systemic features and aortic disease (dilatation/dissection) in 35% of patients. No deaths occurred from cardiovascular events or pregnancy-related complications. Nevertheless, homozygosity may be driving a more severe phenotype. Show less
Hartog, A.W. den; Franken, R.; Zwinderman, A.H.; Timmermans, J.; Scholte, A.J.; Berg, M.P. van den; ... ; Groenink, M. 2015
