Baseline AVSD Echo Descriptive Analysis Fall Work Weekend November 18, 2016 James M. Meza, MD and David M. Overman, MD (Study PI) This is first look at this – really need more involvement, want thoughts

Measures of Inflow Physiology Modified atrioventricular valve index (Cohen 1996 and Jegatheeswaran, 2010) Portion of AV valve allocated to each ventricular in the subxiphoid saggital ro LAO view Retrospective CHSS study – identified RV/LV inflow angle as best discriminator of unbalance (Cohen, 2013) Angle between the base of the right ventricle and left ventricle free wall using the crest of the ventricular septum as the apex of the angle

Measures of Inflow Physiology Left ventricular inflow index = Secondary inflow diameter/Primary inflow diameter (Swazst, 2011) Primary: level of left AVV annulus Secondary: color inflow jet diameter at level of papillary muscles

Present Study Imaging Core Lab (ICL) has been collecting and reading echoes for 2 years Descriptive analysis of baseline diagnostic echoes

AVSD Cohort Inclusion criteria Exclusion criteria Diagnosis of or referral with complete AVSD at a CHSS institution within 1st year of life Admitted to CHSS institution after January 1, 2012 Age ≤ 365 days at admission for surgery Atrioventricular and ventriculoarterial concordance Includes Tetralogy of Fallot and Double Outlet Right Ventricle Exclusion criteria Partial or Transitional AVSD Separate AV valve orifices, restrictive VSD or intact ventricular septum TAPVC or PAPVC, aortic atresia, Heterotaxy First Intervention at a non-CHSS institution

Study Population 328 enrolled patients,149 with echoes read (59%) Mean   Mean Std Median IQR Min-Max Demographics Age at echo 48 68 15 1-83 0-544 Height 51.6 6.3 50.0 48.0-56.0 34.0-67.3 Weight 3.6 1.2 3.3 2.8-4.2 1.3-8.3 BSA 0.2 0.05 0.2-0.3 0.1-0.4

Clinical characteristics   Frequency Complete AVSD (unrestrictive VSD) 100% AV concordance VA concordance Normal pulmonary venous connection 99.5% (193/194) Normal systemic venous connection Additional Diagnosis Tetralogy of Fallot 7% (13/194) Systemic venous anomalies 3% (5/193) LSVC to CS 7% (13/185) LSVC Unroofed to LA 0% Bilateral SVCs 6% (11/183) Interrupted IVC to RSVC/LSVC

Echo Review Protocol Single reviewer – Cheryl Fakhoury 111 parameters

Atrial and Ventricular Septae   Frequency Malalignment of atrial and ventricular septum 15% (25/186) Right (double outlet LA) 8% (2/25%) Left (double outlet LA) 92% (23/25) Ostium primum ASD 99.5% (193/194) Primum ASD restrictive 2% (4/192)   Mean Std Median IQR Min-Max ASD size 0.7 0.4 0.6 0.4-0.9 0.1-2.3 Inlet VSD size: From PSSAx (cm) 0.2 0.5-0.7 0.2-1.1 Inlet VSD size: From Apical 4 (cm) 0.5-0.8 0.2-1.3

Common AV Valve Mean Std Median IQR Min-Max Mural leaflet length 1.4   Mean Std Median IQR Min-Max Mural leaflet length 1.4 0.4 1.3 1.1-1.6 0.6-2.4 Mural leaflet width 0.9 0.2 0.7-1.0 0.4-1.5 Total CAVV diameter 2.4 2.1-2.7 0.9-3.6 RAVV area 1.7 0.7 1.6 1.2-2.1 0.4-4.8 LAVV area 0.6 1.2 0.9-1.7 0.4-3.7 Total area 3.1 1.1 3.0 2.2-3.8 1.1-7.9 2D measurement RAVV (apical 4) (cm) 0.3 1.2-1.6 0.6-2.3 Color inflow diameter at annulus RAVV (cm) 1.5 1.3-1.7 0.9-2.4 Color inflow diameter at mid cavity or at smallest inflow portion RAVV(cm) 0.8 0.7-0.9 2D measurement LAVV (apical 4) (cm): 1.1-1.4 0.6-1.8 Color inflow diameter at annulus (cm) 1.1-1.5 0.4-2.1 Color inflow diameter at mid cavity or at smallest inflow portion (cm) 0.6-0.8 0.1-1.9 Distance between two papillary muscles: (cm) 1.0-1.5 0.5-2.0

Inflow Characteristics   Mean Std Median IQR Min-Max mAVVI 0.45 0.10 0.44 0.39-0.51 0.18-0.69 RV inflow – LV inflow angle 91.0 15.8 89.0 80.0-101.3 52.1-132.1 Left ventricular inflow index 0.5 0.1 0.5-0.6 0.3-1.2   Frequency Right-dominant 22% (42/194) Balanced 53% (108/194) Left dominant 5% (9/194) Unable to determine (no mAVVI) 21% (41/194)

RV/LV inflow angle (degrees) 145+12 113+9 81+9

  Frequency Common AV Valve Regurgitation Trivial 6% (11/194) Mild 68% (132/194) Moderate 22% (42/194) Severe 5% (9/194) Left AV Valve regurgitation None 11% (22/193) 18% (35/193) 62% (120/193) 8% (15/193) 1% (1/193) Right AV Valve regurgitation 2% (4/193) 30% (57/193) 50% (97/193) 15% (29/193) 3% (6/193) Rastelli Type A 79% (66/84) B 2% (2/84) C 19% (16/84) Papillary muscle abnormality 32% (56/189) Too close 30% (17/56) One hypoplastic 70% (39/56) Parachute 0% Double orifice LAVV 0.6% (1/160)

Right Ventricle Mean Std Median IQR Min-Max RV Area in End - Diastole (4 chamber view) (cm2) 4.3 1.5 4.0 3.2-5.3 1.5-8.3 RV Area in End - Systole (4 chamber view) (cm2) 2.8 1.0 2.7 2.1-3.4 0.8-5.6 Right Ventricle Fractional Area Change (Calculated field) (%) 35.3 7.7 34.5 30.7-39.1 0-75.9 RV length From AV Valve to apex (at end of QRS complex) (cm) 0.5 2.5-3.2 1.5-4.2 RV width (from the crest of the septum- RV side- to the free wall) (cm) 1.6 0.4 1.3-1.8 0.3-2.5   Frequency  RV hypoplasia None 88% (170/194) Trivial 3% (6/194) Mild 4% (7/194) Moderate 4% (8/194) Severe 1% (3/194) RV systolic dysfunction 97% (188/193) 2% (4/193) 1% (1/193) Apex-forming RV 93% (179/192)

Pulmonic Valve Mean Std Median IQR Min-Max PV Annulus in systole (cm) 1.0 0.2 0.9-1.1 0.3-1.4 Frequency  PV stenosis   None 90% (170/194) Trivial 0.5% (1/194) Mild 4% (7/194) Moderate 4% (8/194) Severe 1.5% (3/194) PV regurgitation 39% (75/194) 47% (91/194) 14% (28/194)

RVOT Mean Std Median IQR Min-Max Peak gradient (mmHg) 36.5 27.4 27.2 15.2-54.4 6.9-109.8 Mean gradient (mmHg) 22.1 17.8 18.7 7.5-34.1 4.1-70.1 Frequency  RVOT Obstruction 9% (16/183) Subvalvar 44% (7/16) Valvar 13% (2/16) Supravalvar 6% (1/16) Diffuse 38% (6/16)

Left Ventricle Frequency LV hypoplasia None 90% (174/194) Trivial   None 90% (174/194) Trivial 0.5% (1/194) Mild 3% (6/194) Moderate Severe 3.5% (7/194) Apex-forming LV 94% (181/192) LV dysfunction Systolic 95% (183/192) 3% (6/192) 1% (2/192) 1% (1/192)

Left Ventricle Mean Std Median IQR Min-Max LVEDD (cm) 1.8 0.5 1.6-2.1 0.5-3.4 LVESD (cm) 1.1 0.3 0.9-1.3 0.3-2.5 LVEF (%) 71.1 9.3 72.0 65.8-78.0 33.3-92.9 LV area in End-Diastole (4 chamber view): (cm2) 4.4 1.7 3.3-5.5 0.9-8.8 LV area in End-Systole (4 chamber view): (cm2) 2.4 0.9 2.3 1.8-3.0 0.6-5.1 Left Ventricle Fractional Area Change (calculated field): (%) 43.3 7.5 43.5 39.6-48.0 18.4-63.4 LV length from AVV to apex (at end of QRS complex) (cm) 2.9 2.5-3.3 1.3-4.1 LV width (from crest of septum- LV side- to free wall) (cm) 1.6 0.4 1.3-1.8 0.4-2.6

LVOT Frequency Left Ventricular Outflow Tract Obstruction 3% (5/193) LVOTO level of stenosis   Sub-valvar 80% (4/5) Valvar 20% (1/5) LVOTO Type of Subvalvar Stenosis Tunnel 100% LVOTO Type of Supravalvar Stenosis Discrete 25% Diffuse 75% Mean Std Median IQR Min-Max Smallest LVOT diameter in systole (cm) 0.7 0.2 0.6-0.8 0.3-1.1 Peak gradient (mmHg) 5.0 2.2 4.8 2.9-7.3 Mean gradient (mmHg) 2.3 1.3 1.3-3.2

Aortic Valve Mean Std Median IQR Min-Max Aortic Annulus in systole (cm) 0.8 0.2 0.7-0.9 0.3-1.3 Aortic root in systole (cm) 1.0 1.1 0.9-1.2 0.6-1.5 Sinotubular junction in systole (cm) 0.4-1.2

Aortic Valve Frequency Aortic Valve Thickening None 92% (178/193)   None 92% (178/193) Trivial 2% (4/193) Mild 3% (6/193) Moderate 3% (5/193) Number of Leaflets Bi 6% (9/148) Tri 94% (139/148) Stenosis 96% (184/191) 2% (3/191) 2% (4/191) Regurgitation 67% (129/194) 29% (57/194) 4% (8/194)

Aorta Mean Std Median IQR Min-Max Ascending Aorta (measured from parasternal LA view in systole, just above the ST junction): (cm) 0.8 0.1 0.9 0.8-0.9 0.4-1.2 Transverse Arch (cm) 0.5 0.4-0.6 0.2-1.0 Isthmus (cm) 0.4 0.3-0.5 0.2-0.7 Descending aorta (cm) 0.6 0.03 0.6-0.6 Peak Arch gradient (mmHg) 11.1 10.0 6.8 4.8-14.6 1.1-42.0 Mean Arch gradient (mmHg) 6.1 5.6 3.7 2.2-8.5 0.6-22.0

Aorta Frequency Coarctation present 18% (29/158) Location of coarctation   Transverse 7% (2/27) Isthmus 93% (25/27) Interrupted Arch 0% Flow direction in ascending arch: Antegrade 100% Flow direction in transverse arch: 95% (181/190) Retrograde 1% (2/190) Bidirectional 4% (7/190)

Ductus Arteriosus Frequency Ductus patent 61% (116/189) Ductal flow restrictive 55% (62/113) Ductal flow in systole   Left to right 3% (3/98) Right to left 97% (95/98) Ductal flow in diastole 99% (114/115) 1% (1/115)

Correlating inflow physiology and ventricular geometry

Correlations of mAVVI with other indices of inflow physiology   Pearson Correlation Coefficient P-value LVII 0.28 0.001 RV/LV inflow angle 0.12 0.13

Correlations – mAVVI and measures of ventricular geometry   Pearson Correlation Coefficient P-value Color inflow diameter at RAVV annulus -0.29 0.001 Color inflow diameter at LAVV annulus 0.41 < 0.0001 RV end diastolic area -0.31 0.0001 LV end diastolic area 0.43

Correlations – RV/LV inflow angle and measures of ventricular geometry   Pearson Correlation Coefficient P-value Color inflow diameter at RAVV annulus -0.40 < 0.0001 Color inflow diameter at LAVV annulus -0.36 RV end diastolic area 0.08 0.26 LV end diastolic area 0.12 0.11

Correlations – LVII and measures of ventricular geometry   Pearson Correlation Coefficient P-value Color inflow diameter at RAVV annulus -0.26 0.002 RV end diastolic area -0.10 0.22 LV end diastolic area 0.16 0.04

Next steps Exploring impact of septal angulation on ventricular geometry Exploring mural leaflet sizes and ventricular geometry Abnormalities of LAVV apparatus and ventricular geometry Paplliary muscle abnormalities

THANK YOU james.meza@sickkids.ca