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Bicuspid aortic valve (BAV) is the most frequent cardiac congenital valvular disease. Although the BAV risk of first degree relatives (FDR) has been assessed (7-9%), there is little information as to the heritable risk for aortopathy.Identify the specific risk for regional aortopathy in FDR with tricuspid aortic valve (TAV) of BAV patients according to their aortic phenotype and aortic regurgitation (AR).Using an international consortium, BAV probands were assessed for aortopathy of the root, ascending aorta and for AR. Aortopathy was defined by the presence of segmental dilatation. The presence of segmental aortopathy and AR in BAV probands was evaluated as predictor for aortopathy in FDR with TAV.We identified 74 FDR related to 49 probands with aortopathy and 66 FDR related to 31 probands without aortopathy. Demographic variables were similar between proband groups. Among FDR, 16 individuals had BAV (11.4%). TAV-FDR of probands with ascending aortopathy had higher incidence of root aortopathy (18.8% vs. 3.6% p 0.05) while TAV-FDR of probands with root aortopathy had higher incidence of aortopathy at all aortic segments (55%vs25%, 55%vs21%, and 4%vs29% at annulus, root and ascending respectively, p 0.05 for all). Independent predictors for root aortopathy in TAV-FDR were: ascending (OR = 6.23;95%CI:1.27-30.5) and root aortopathy (OR = 9.00;95%CI:1.58-51.1) in probands; and for ascending aortopathy: root aortopathy (OR = 4.04;95%CI:1.33-12.3) and AR in probands (OR = 4.84; 95%CI:1.75-13.4).Root and ascending aortopathy in BAV probands are strong predictors of aortopathy in their TAV-FDR. AR in BAV patients has an independent effect on the risk for ascending aortopathy in TAV-FDR.

Turner Syndrome (TS) is a developmental disorder caused by partial or complete loss of one sex chromosome. Bicuspid aortic valve and other left-sided congenital heart lesions (LSL), including thoracic aortic aneurysms and acute aortic dissections, are 30–50 times more frequent in TS than in the general population. In 454 TS subjects, we found that LSL are significantly associated with reduced dosage of Xp genes and increased dosage of Xq genes. We also showed that genome-wide copy number variation is increased in TS and identify a common copy number variant (CNV) in chromosome 12p13.31 that is associated with LSL with an odds ratio of 3.7. This CNV contains three protein-coding genes (SLC2A3, SLC2A14, and NANOGP1) and was previously implicated in congenital heart defects in the 22q11 deletion syndrome. In addition, we identified a subset of rare and recurrent CNVs that are also enriched in non-syndromic BAV cases. These observations support our hypothesis that X chromosome and autosomal variants affecting cardiac developmental genes may interact to cause the increased prevalence of LSL in TS. © 2016 Wiley Periodicals, Inc.

Objective To examine the hypothesis that speckle myocardial imaging (SMI) modalities, including longitudinal, radial and circumferential systolic (s) and diastolic (d) myocardial velocity imaging, displacement (D), strain rate (SR) and strain (S), as well as left ventricular (LV) rotation/torsion are sensitive for detecting early myocardial dysfunction in isolated LV non-compaction (iLVNC). Design and results Twenty patients with iLVNC diagnosed by cardiac magnetic resonance (15) or echocardiography (5) were included. Patients were divided into two groups: ejection fraction (EF)>50% (n=10) and EF≤50% (n=10). Standard measures of systolic and diastolic function including pulsed wave tissue Doppler Imaging (PWTDI) were obtained. Longitudinal, radial and circumferential SMI, and LV rotation/torsion were compared with values for 20 age/sex-matched controls. EF, PWTDI E9, E/E9 and all of the SMI modalities were significantly abnormal for patients with EF≤50% compared with controls. In contrast, EF and PWTDI E9, E/E9 were not significantly different between controls and patients with iLVNC (EF>50%). However, SMI-derived longitudinal sS, sSR, sD and radial sS, as well as LV rotation/torsion values, were all reduced in iLVNC (EF>50%) compared with controls. Measurements with the highest discriminating power between iLVNC (EF>50%) and controls were longitudinal sS mean of the six apical segments (area under the curve (AUC)=0.94), sS global average (AUC=0.94), LV rotation apical mean (AUC=0.94); LV torsion (AUC=0.93) LV torsion rate (AUC=0.94). Conclusions LV SMI values are reduced in patients with iLVNC, even those with normal EF and PWTDI. The most accurate SMI modalities to discriminate between patients and controls are longitudinal sS mean of the six apical segments, LV apical rotation or LV torsion rate.