Inherited extremes of aortic diameter confer risk for a specific class of congenital heart disease.

Population based studies demonstrate strong familial recurrence of cardiac malformations particularly for individuals affected with a specific class of CHD, left-ventricular outflow tract (LVOT) obstruction. Recently we linked 99 lead variants across 71 loci to diameter of the ascending aorta derived from MRI measurements across multiple ethnicities in the UK Biobank. Using these data we created a polygenic risk score capturing ascending aortic diameter (PRSAoD) Among 2,594 individuals with CHD; a decrease by one standard deviation in PRSAoD was associated with an increased risk of congenital LVOT (OR=1.14[1.03-1.26], p=0.014) but not with other subtypes of CHD. Using Mendelian Randomization we observed strong evidence of a causal effect where inheritance of a smaller diameter of the ascending aorta corresponded to an increase in risk for congenital LVOT (p_IVW = 0.008). Our data may suggest that genetic determinants of a smaller ascending aorta act during early development to disturb blood flow through left-sided structures to increasing the risk of LVOT CHD, which is consistent with experimental evidence and the "no flow, no grow" paradigm in the formation of the left ventricular outflow tract.

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The axial cine image shows a large channel arising from proximal ascending aorta just above the right aortic sinus which is seen to communicate with the left ventricular outflow tract at its distal end

ASVIDE ◽

10.21037/asvide.2018.008 ◽

2018 ◽

Vol 5 ◽

pp. 008-008

Author(s):

Sarv Priya ◽

Gurpreet S. Gulati ◽

Anita Saxena ◽

Balram Airan

Keyword(s):

Left Ventricular Outflow Tract ◽

Ventricular Outflow Tract ◽

Left Ventricular ◽

Ascending Aorta ◽

Outflow Tract ◽

Cine Image ◽

Aortic Sinus ◽

Large Channel ◽

Left Ventricular Outflow ◽

The Right

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Abstract 4569: What is the Best Operation for Transposition of the Great Arteries with Left Ventricular Outflow Tract Obstruction?: Midterm results

Circulation ◽

10.1161/circ.118.suppl_18.s_913-a ◽

2008 ◽

Vol 118 (suppl_18) ◽

Author(s):

Sitaram M Emani ◽

Rebecca Beroukhim ◽

David Zurakowski ◽

Frank A Pigula ◽

Pedro J del Nido ◽

...

Keyword(s):

Left Ventricular Outflow Tract ◽

Arterial Switch Operation ◽

Ventricular Outflow Tract ◽

Left Ventricular ◽

Outflow Tract ◽

High Rate ◽

Z Score ◽

Ventricular Outflow Tract Obstruction ◽

Increased Risk ◽

Left Ventricular Outflow

Transposition of the great arteries (TGA) with left ventricular outflow tract obstruction (LVOTO) may be treated with arterial switch operation (ASO) with or without LVOT intervention, aortic translocation, or Rastelli operation. We evaluated mid-term results of repair for TGA/LVOTO at our institution. Patients diagnosed with TGA/LVOTO at Children’s Hospital Boston from 1995 to 2007 who underwent repair were retrospectively reviewed. LVOTO was defined as pulmonary valve (PV) z-score < −2.0 or LVOT gradient > 15 mmHg in the presence of anatomic subvalvar stenosis. Preoperative morphology of the LVOT and PV were recorded. Kaplan-Meier freedom from LVOT reintervention was compared between groups and risk factors were determined by logistic regression. 88 patients with TGA/LVOTO were repaired. Ventricular septal defect was present in 78 (89%). Patients with lower PV z-scores at presentation were more likely to undergo Rastelli or aortic translocation as opposed to ASO ± LVOT intervention. At median follow up of 2.7 years (range 8 mo to 11 yrs), all patients were alive. Patients undergoing Rastelli were more likely to require surgical reintervention for LVOTO compared to the other groups ( P =0.015, log-rank=10.49). Patients undergoing ASO alone had a higher rate of LVOT reintervention than those who had concomitant LVOT intervention ( P =NS). In those undergoing Rastelli, a higher PV z-score was a predictor of LVOT reintervention (odds ratio = 4.0, P =0.012). TGA patients with severe LVOTO who undergo Rastelli repair have a high rate of LVOT reintervention. Higher preoperative PV z-score is a risk factor for reintervention in this group. Patients with mild/moderate LVOTO undergoing ASO alone may have an increased risk of LVOT reintervention.

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