Histopathology of aortic complications in bicuspid aortic valve versus Marfan syndrome: relevance for therapy?

Patients with bicuspid aortic valve (BAV) and patients with Marfan syndrome (MFS) are more prone to develop aortic dilation and dissection compared to persons with a tricuspid aortic valve (TAV). To elucidate potential common and distinct pathways of clinical relevance, we compared the histopathological substrates of aortopathy. Ascending aortic wall biopsies were divided in five groups: BAV (n = 36) and TAV (n = 23) without and with dilation and non-dilated MFS (n = 8). General histologic features, apoptosis, the expr

Common arterial trunk and ventricular non-compaction in Lrp2 knockout mice indicate a crucial role of LRP2 in cardiac development

Lipoprotein-related receptor protein 2 (LRP2) is important for development of the embryonic neural crest and brain in both mice and humans. Although a role in cardiovascular development can be expected, the hearts of Lrp2 knockout (KO) mice have not yet been investigated. We studied the cardiovascular development of Lrp2 KO mice between embryonic day 10.5 (E10.5) and E15.5, applying morphometry and immunohistochemistry, using antibodies against Tfap2α (neural crest cells), Nkx2.5 (second heart field), WT1 (epicardium derived cells), tropomyosin (myocardium) and LRP2. The Lrp2 KO mice display a range of severe cardiovascular abnormalities, including aortic arch anomalies, common arterial trunk (persistent truncus arteriosus) with coronary artery anomalies, ventricular septal defects, overriding of the tricuspid valve and marked thinning of the ventricular myocardium. Both the neural crest cells and second heart field, which are essential for the lengthening and growth of the right ventricular outflow tract, are abnormally positioned in the Lrp2 KO. T hi s explains the absence of the aorto-pulmonary septum, which leads to common arterial trunk and ventricular septal defects. Severe blebbing of the epicardial cells covering the ventricles is seen. Epithelial-mesenchymal transition does occur; however, there are fewer WT1-positive epicardium-derived cells in the ventricular wall as compared to normal, coinciding with the myocardial thinning and deep intertrabecular spaces. LRP2 plays a crucial role in cardiovascular development in mice. This corroborates findings of cardiac anomalies in humans with LRP2 mutations. Future studies should reveal the underlying signaling mechanisms in which LRP2 is involved during cardiogenesis

Stress increases intracardiac 4D flow cardiovascular magnetic resonance -derived energetics and vorticity and relates to VO2max in Fontan patients

BACKGROUND: We hypothesize that dobutamine-induced stress impacts intracardiac hemodynamic parameters and that this may be linked to decreased exercise capacity in Fontan patients. Therefore, the purpose of this study was to assess the effect of pharmacologic stress on intraventricular kinetic energy (KE), viscous energy loss (EL) and vorticity from four-dimensional (4D) Flow cardiovascular magnetic resonance (CMR) imaging in Fontan patients and to study the association between stress response and exercise capacity. METHODS: Ten Fontan patients underwent whole-heart 4D flow CMR before and during 7.5 μg/kg/min dobutamine infusion and cardiopulmonary exercise testing (CPET) on the same day. Average ventricular KE, EL and vorticity were computed over systole, diastole and the total cardiac cycle (vorticity_volavg cycle, KEavg cycle, ELavg cycle). The relation to maximum oxygen uptake (VO2 max) from CPET was tested by Pearson's correlation or Spearman's rank correlation in case of non-normality of the data. RESULTS: Dobutamine stress caused a significant 88 ± 52% increase in KE (KEavg cycle: 1.8 ± 0.5 vs 3.3 ± 0.9 mJ, P < 0.001), a significant 108 ± 49% increase in EL (ELavg cycle: 0.9 ± 0.4 vs 1.9 ± 0.9 mW, P < 0.001) and a significant 27 ± 19% increase in vorticity (vorticity_volavg cycle: 3441 ± 899 vs 4394 ± 1322 mL/s, P = 0.002). All rest-stress differences (%) were negatively correlated to VO2 max (KEavg cycle: r = - 0.83, P = 0.003; ELavg cycle: r = - 0.80, P = 0.006; vorticity_volavg cycle: r = - 0.64, P = 0.047). CONCLUSIONS: 4D flow CMR-derived intraventricular kinetic energy, viscous energy loss and vorticity in Fontan patients increase during pharmacologic stress and show a negative correlation with exercise capacity measured by VO2 max

Coding of coronary arterial origin and branching in congenital heart disease: The modified Leiden Convention

Objectives: Variations in coronary anatomy are common and may relate to the position of the coronary ostium relative to the aortic sinus, the angle of coronary take-off, or the course of the coronary arterial branches. Several classification systems have been proposed. However, they all lack a simple rationale that is applicable irrespective of the relative position of the great arteries, as well as in bicuspid aortic valves. We present a modification of a relatively simple system introduced in the early 1980s, designated the “Leiden Convention.” Methods: The first step of the Leiden Convention is that the clinician takes position in the nonfacing sinus of the aorta looking toward the pulmonary orifice. The right-hand facing sinus is sinus 1, and the left-hand facing sinus is sinus 2. The coronary branches arising from sinus 1 are annotated proceeding in a counterclockwise fashion toward sinus 2. “Usual” (normal) coronary anatomy would be 1R-2LCx. Given their clinical relevance, single sinus coronary arteries are discussed separately. Results: This system was originally designed and highly applicable in hearts with an altered great artery relationship, such as in the var

Reduced right ventricular function on cardiovascular magnetic resonance imaging is associated with uteroplacental impairment in tetralogy of Fallot

BACKGROUND: Maternal right ventricular (RV) dysfunction (measured by echocardiography) is associated with impaired uteroplacental circulation, however echocardiography has important limitations in the assessment of RV function. We therefore aimed to investigate the association of pre-pregnancy RV and left ventricular (LV) function measured by cardiovascular magnetic resonance with uteroplacental Doppler flow parameters in pregnant women with repaired Tetralogy of Fallot (ToF). METHODS: Women with repaired ToF were examined, who had been enrolled in a prospective multicenter study of pregnant women with congenital heart disease. Clinical data and CMR evaluation before pregnancy were compared with uteroplacental Doppler parameters at 20 and 32 weeks gestation. In particular, pulsatility index (PI) of uterine and umbilical artery were studied. RESULTS: We studied 31 women; mean age 30 years, operated at early age. Univariable analyses showed that reduced RV ejection fraction (RVEF; P = 0.037 and P = 0.001), higher RV end-systolic volume (P = 0.004) and higher LV end-diastolic and end-systolic volume (P = 0.001 and P = 0.003, respectively) were associated with higher uterine or umbilical artery PI. With multivariable analyses (corrected for maternal age and body mass index), reduced RVEF before pregnancy remained associated with higher umbilical artery PI at 32 weeks (P = 0.002). RVEF was lower in women with high PI compared to women with normal PI during pregnancy (44% vs. 53%, p = 0.022). LV ejection fraction was not associated with uterine or umbilical artery PI. CONCLUSIONS: Reduced RV function before pregn