Can Fetal Echocardiographic Measurements of the Left Ventricular Outflow Tract Angle Detect Fetuses with Conotruncal Cardiac Anomalies?

Objectives: The angle between the inter-ventricular septum and the ascending aorta can be measured during a sonographic fetal survey while viewing the left ventricular outflow tract (LVOT angle). Our aim was to compare the LVOT angle between fetuses with and without conotruncal cardiac anomaliesrmations. Methods: In this prospective observational study, we compared the LVOT angle between normal fetuses, at different gestational age, and fetuses with cardiac malformations. Results: The study included 302 fetuses screened at gestational age of 12–39 weeks. The LVOT angle ranged from 127 to 163 degrees (mean 148.2), in 293 fetuses with normal hearts, and was not correlated with gestational age. The LVOT angle was significantly wider in fetuses with D-transposition of the great arteries (D-TGA, eight fetuses) and valvar aortic stenosis (AS, three fetuses), than in fetuses with normal hearts (164.8 ± 5.0 vs. 148.2 ± 5.4, respectively, p < 0.001). Conversely, the LVOT angle was significantly narrower in fetuses with complete atrioventricular canal defect (AVC, eight fetuses), than in fetuses with normal hearts (124.8 ± 2.4 vs. 148.2 ± 5.4, respectively, p < 0.001). On ROC analysis, an angle of 159.6 degrees or higher had a sensitivity of 100% and a specificity of 97.3% for the detection of TGA or AS, whereas an angle of 128.8 degrees or lower had a sensitivity of 100% and a specificity of 99.7% for the detection of AVC defect. Conclusions: The LVOT angle is constant during pregnancy, and differs significantly in fetuses with TGA/AS, and AVC, compared to fetuses with normal hearts (wider and narrower, respectively).

Genetic Diagnosis and the Severity of Cardiovascular Phenotype in Patients With Elastin Arteriopathy

Background: Elastin insufficiency causes recurrent vascular stenoses. Hemizygous deletion of the elastin gene ( ELN ) causes Williams-Beuren syndrome (WBS), while single nucleotide variants in ELN cause nonsyndromic supravalvar aortic stenosis (SVAS). Our objective was to compare cardiovascular disease outcomes in patients with WBS and nonsyndromic SVAS. Methods: Patients (81 WBS, 42 nonsyndromic SVAS) with cardiovascular disease were included in this retrospective single center study. Freedom from surgical and catheter interventions and reinterventions was compared. Vascular tissue from 8 patients and 6 controls was analyzed for arterial wall architecture. Results: Patients with nonsyndromic SVAS presented at a younger age (median 0.3 [0.4–0.7] years) compared with patients with WBS (1.3 [0.2–3.0] years) and had lower freedom from surgical/catheter interventions compared with patients with WBS, with median event-free survival 1.1 (0.3–5.9) versus 4.7 (2.4–13.3) years, respectively (hazard ratio, 1.62 [95% CI, 1.02–2.56]; P =0.04). Patients with nonsyndromic SVAS also had a lower freedom from reinterventions ( P =0.054 by log-rank test). This was related in part to a higher frequency of primary and reinterventions for concomitant valvar aortic stenosis. Histology revealed abnormal intimal and medial thickening, disorganized and fragmented elastic fibers, reduced smooth muscle calponin expression, and increased macrophage marker, CD68, expression in the arterial walls in patients with WBS and nonsyndromic SVAS compared with controls. Conclusions: Patients with nonsyndromic SVAS require early and more frequent vascular and valvular interventions and reinterventions, in particular for concomitant valvar aortic stenosis compared with patients with WBS. This provides important prognostic information to guide counseling of affected families with cardiovascular disease and may guide primary intervention strategies based on predicted risk of restenosis.

The following is the abstract of the article discussed in the subsequent letter:

Wall stress, although commonly used as an index of afterload, fails to take into account forces generated within the wall of the left ventricle (LV) that oppose systolic fiber shortening. Wall stress may, therefore, misrepresent fiber stress, the force resisting fiber shortening, particularly in the presence of an abnormal LV thickness-to-dimension ratio ( h/ D). M-mode LV echocardiograms were obtained from 207 patients with a wide range of values for LV mass and/or h/ D. Diagnoses were valvar aortic stenosis, coarctation repair, anthracycline treated, and severe aortic and/or mitral regurgitation. End-systolic wall stress (WSes) and fiber stress (FSes) were expressed as age-corrected Z scores relative to a normal population. The difference between WSes and FSes was extreme when h/ D was elevated or reduced [WSes Z score − FSes Z score = 0.14 × ( h/ D)−1.47 − 2.13; r = 0.78, P < 0.001], with WSes underestimating FSes when h/ D was increased and overestimating FSes when h/ D was decreased. Analyses of myocardial mechanics based on wall stress have limited validity in patients with abnormal ventricular geometry.