Aortic root pathology has been described in patients with Tetralogy of Fallot, although the most common reason for repeat surgery in the adult after TOF repair relates to problems in the right ventricular outflow tract, the aortic root is often forgotten. Objective: We sought to determine those patients with known Fallot tetrallogy at risk for progressive dilatation of the thoracic aorta and explore the common predictors present in this patient group. Methods and Results: A multicenter observational study which enrolled 100 patients (50 surgically repaired and 50 before surgical repair of TOF) with standardized reassessment of echocardiographic parameters and multislice CT angiography of the heart and great vessels data. The data were reviewed and analyzed according to the demographic, morphological, surgical and clinical details. We used standard nomograms and Z score for aortic root dimensions at the level of aortic annulus, sino-tubular junction and sinus of Valsalva based on body surface area. For surgically repaired patients, all the measured diameters across aortic annulus, STJ & sinus of Valsalva were larger in the dilated unrepaired group with mean & median of 24.63 (3.99) & 25 (15 - 35), 27.2 (4.26) & 27 (17 - 40), 35.97 (4.59) & 36 (24 - 45) mm respectively compared to a mean & median of 13.2 (2.62) & 13 (9 - 17), 14.53 (2.90) & 14 (10 - 19), 20.53 (3.40) & 21 (14 - 25) mm respectively in the not dilated unrepaired group with significant statistical difference (p value < 0.0001). Also Z score among unrepaired dilated TOF patients was larger in comparison to the non dilated unrepaired group with significant statistical difference (p value < 0.0001). For unrepaired patients, all the measured diameters across aortic annulus, STJ & sinus of Valsalva were larger in the dilated unrepaired group with mean & median of 24.63 (3.99) & 25 (15 - 35), 27.2 (4.26) & 27 (17 - 40), 35.97 (4.59) & 36 (24 - 45) mm respectively compared to a mean & median of 13.2 (2.62) & 13 (9 - 17), 14.53 (2.90) & 14 (10 - 19), 20.53 (3.40) & 21 (14 - 25) mm respectively in the not dilated unrepaired group with significant statistical difference (p value < 0.0001). Also Z score among unrepaired dilated TOF patients at the level of annulus, STJ & sinus of Valsalva was larger in comparison to the non dilated unrepaired group with significant statistical difference (p value < 0.0001). Conclusions: The first important finding of this study is the occurrence of significant aortic root dilatation in 22% of patients after intra-cardiac repair of TOF. Older age at repair, long shunt to repair interval and residual ventricular septal defect are the most common variables associated with aortopathy and aortic regurgitation in such group of patients. The second important finding is the occurrence of aortic root dilatation in 70% of patients before surgical repair of TOF; whereas male sex and TOF with pulmonary atresia appeared to be the most common variables associated with aortopathy and aortic regurgitation in this group of patients.
Tetralogy of Fallot (TOF) is the most commonly encountered cyanotic congenital heart defect in infancy, with a frequency of nearly 10% of all congenital heart disease [
The study reviewed echocardiographic and multislice CT angiography of the heart and great vessels data obtained from 100 patients with known Fallot Tetralogy associated with aortopathy attending the outpatient congenital cardiac clinic at Beni-Suef University Hospital and National Heart Institute. The data were reviewed and analyzed according to the demographic, morphological, surgical and clinical details. Patients were excluded if they had coexisting complex congenital abnormalities (single ventricle physiology or transposition of the great arteries) and connective tissue disorder. No case had prior aortic root or valve repair [
Patient charts were reviewed for age, sex, body surface area (BSA), degree of cyanosis as evaluated with pulse oximetry, prior interventions, age at intervention and duration of follow up after intervention, and residual cardiac lesions.
Aortic root size was measured from M-mode or 2D echo according to American Society of Echocardiography guidelines [
MSCT was performed with a 64-MDCT scanner (Siemens, somatom, dual source 64, rotation time 0.33 sec, temporal resolution 80 - 83 msec, Germany). MSCT images were analyzed retrospectively, slice thickness 0.5 mm, overlap 0.3 mm. Increment during data acquisition: 1.5 mm Multiplanar reconstruction (MPR), curved- planar reconstruction (CPR), volume render (VR), maximum intensity projection (MIP) and minimum intensity projection (MinIP) were performed in all patients. Intravenous injection of 11 ml of iodixanol 370 through an antecubital vein at a high flow rate {2.5 ml/sec.} was done. An 80 kv was selected in patients less than one year old for CT examination to reduce radiation exposure [
Data analysis was performed using STATA intercooled version 9.2. Quantitative data were analyzed using student t-test to compare means of two groups. When the data were not normally distributed Mann-Whitney test was used. Qualitative data were compared using either Chi square test or Fisher exact test. Statistical significance was inferred if p-value was less than 0.05.
The current study is an observational analysis of Tetralogy of Fallot patients. The study was conducted in Benisuef University Hospital and National Heart Institute with the aim to identify predictors for aortic root dilatation in Tetralogy of Fallot (ToF) patients. The current study enrolled 100 patients (50 surgically repaired and 50 before surgical repair of TOF).
This group include 50 patients, their mean age is 164.48 (78.04) months & median (range) 156 (36 - 325) months, with male predominance 64% (no = 32 pt), their mean height & weight is 137.7 (27.27) cm & 40.99 (17.56) kg respectively with median 146.5 (83 - 179) cm & 40 (14 - 72) kg (
Characteristics | No. (%) |
---|---|
Age <96 months ≥96 months | 10 (20.00) 40 (80.00) |
Sex Female Male | 18 (36.00) 32 (64.00) |
Height Mean (SD) Median (range) | 137.7 (27.27) 146.5 (83 - 179) |
Weight Mean (SD) Median (range) | 40.99 (17.56) 40 (14 - 72) |
Characteristics | No. (%) |
---|---|
Conduit repair of pulmonary Artesia No Yes | 48 (96) 2 (4) |
Arch side Left Right | 35 (70.00) 15 (30.00) |
Associated disease No Absent pulmonary valve | 49 (98.00) 1 (2.00) |
Characteristics | No. (%) |
---|---|
BSA (m2) Mean (SD) Median (range) | 1.23 (0.39) 1.26 (0.55 - 1.89) |
O2 saturation (%) Mean (SD) Median (range) | 91.52 (3.19) 91.5 (84 - 98) |
O2 saturation (%) <80 ≥80 | 0 (0.00) 50 (100.00) |
(
Characteristics | No. (%) |
---|---|
Age at repair (months) Mean (SD) Median (range) | 73.1 (42.86) 60 (12 - 186) |
Shunt duration (months) Mean (SD) Median (range) | 143.1 (57.79) 129 (72 - 264) |
Repair duration (months) Mean (SD) Median (range) | 91.38 (49.99) 84 (12 - 210) |
Shunt repair interval (months) Mean (SD) Median (range) | 41.7 (27.84) 33 (12 - 108) |
Residual VSD shunt No Yes | 46 (92.00) 4 (8.00) |
Our repaired tetrallogy of Fallot cases were further divided into two subgroups as regard presence of aortic root dilatation defined as aortic root Z score >3 at the level of aortic annulus, sinus of Valsalva & >2.5 at the level of STJ (
Characteristics | No. (%) |
---|---|
LVEF% Mean (SD) Median (range) | 60.68 (5.53) 62 (48 - 70) |
AR No Yes | 42 (84.00) 8 (16.00) |
PR No Yes | 24 (48.00) 26 (52.00) |
RVOT obstruction Mean (SD) Median (range) | 22.68 (11.66) 20 (6 - 62) |
RVOT obstruction <25 mmhg ≥25 mmhg | 33 (66.00) 17 (34.00) |
PASP mmhg Mean (SD) Median (range) | 47.4 (14.55) 44 (25 - 93) |
Characteristics | No. (%) |
---|---|
aortic annulus Mean (SD) Median (range) | 20.72 (4.31) 20.5 (13 - 29) |
Z score Mean (SD) Median (range) | 2.21 (1.17) 2.33 (0.08 - 4.45) |
STJ Mean (SD) Median (range) | 22.96 (4.65) 22.5 (14 - 33) |
Z score Mean (SD) Median (range) | 1.80 (0.89) 1.87 (0.11 - 3.57) |
Sinus of valsalva Mean (SD) Median (range) | 30.14 (6.13) 29.5 (18 - 42) |
Z score Mean (SD) Median (range) | 2.65 (1.04) 2.7 (0.4 - 4.98) |
MAPCS/PDA No + | 50 (100.00) 0 (0.00) |
Conclusion Dilated Not dilated | 11 (22.00) 39 (78.00) |
males representing 72.73% (
Characteristics | Dilated | Not dilated | p value |
---|---|---|---|
Age <96 months >96 months | 1 (9.09) 10 (90.91) | 9 (23.08) 30 (76.92) | 0.31 |
Sex Female Male | 3 (27.27) 8 (72.73) | 15 (38.46) 24 (61.54) | 0.50 |
Height Mean (SD) Median (range) | 144.18 (23.36) 149 (105 - 175) | 135.87 (28.29) 132 (83 - 179) | |
Weight Mean (SD) Median (range) | 45.64 (17.71) 45 (18 - 72) | 39.67 (17.51) 35 (14 - 71) |
Characteristics | Dilated | Not dilated | p value |
---|---|---|---|
Conduit repair of pulmonary Artesia No Yes | 9 (81.82) 2 (18.18) | 39 (100.00) 0 (0.00) | 0.007* |
Arch side Left Right | 5 (45.45) 6 (54.55) | 30 (76.92) 9 (23.08) | 0.04* |
Tab association No Absent pulmonary valve | 10 (90.91) 1 (9.09) | 39 (100.00) 0 (0.00) | 0.06 |
Characteristics | Dilated | Not dilated | p value |
---|---|---|---|
BSA Mean (SD) Median (range) | 1.33 (0.38) 1.37 (0.71 - 1.87) | 1.20 (0.40) 1.16 (0.55 - 1.89) | 0.35 |
O2 saturation Mean (SD) Median (range) | 89 (3.41) 88 (84 - 95) | 92.23 (2.79) 92 (86 - 98) | 0.007* |
O2 saturation <80 ≥80 | 0 (0.00) 11 (100.00) | 0 (0.00) 39 (100.00) |
Characteristics | Dilated | Not dilated | p value |
---|---|---|---|
Age at repair Mean (SD) Median (range) | 112.36 (44.50) 126 (36 - 186) | 62.03 (35.71) 48 (12 - 162) | 0.001* |
Shunt duration Mean (SD) Median (range) | 174 (72.50) 192 (72 - 264) | 132.8 (50.75) 108 (84 - 240) | 0.27 |
Repair duration Mean (SD) Median (range) | 76.91 (54.26) 60 (12 - 180) | 95.46 (48.69) 90 (15 - 210) | 0.24 |
Shunt repair interval Mean (SD) Median (range) | 84 (16.97) 84 (60 - 108) | 27.6 (10.83) 24 (12 - 48) | 0.009* |
Residual VSD shunt No Yes | 7 (63.64) 4 (36.36) | 39 (100.00) 0 (0.00) | <0.0001* |
mean & median of 61.95 (4.32) & 61.95 (4.32)% in the non-dilated group. Among repaired dilator TOF patients, there was a statistically significant higher residual RVOT gradient with mean & median of 33.09 (17.66) & 27 (15 - 62) mmHg with mean & median gradient of 19.74 (7.28) & 19 (6 - 35) mmHg in the repaired non-dilated group. On measuring the PASP, mean & median values were 61.18 (18.27) and 62 (38 - 93) mmHg among dilated group compared to a mean & median PASO of 43.51 (10.71) and 43 (25 - 78) mmHg in the non-dilated group with p value = 0.001. Eight patients 72% of the dilated group had AR of less than moderate while none of the patients in the non-dilated group showed AR and this was of statistically significant value (P < 0.0001). Pulmonary regurgitation was present in 81% (no = 9 pt) of the dilated group compared to 43% of the non-dilated group and this was also of statistically significant value (p 0.03) (
This group included 50 patients before undergoing any reparative surgery, their mean age at presentation was 138.06 (82.04) months & median (range) 126 (12 - 312) months, with male predominance 70% (no = 35 pt), their mean height & weight 123.51 (30.87) cm & 34.17 (18.41) kg respectively with median 126.5 (61 - 168) cm
Characteristics | Dilated | Not dilated | p value |
---|---|---|---|
EF% Mean (SD) Median (range) | 56.18 (7.11) 58 (48 - 65) | 61.95 (4.32) 62 (55 - 70) | 0.03* |
AR No Yes | 3 (27.27) 8 (72.73) | 39 (100.00) 0 (0.00) | <0.0001* |
PR No Yes | 2 (18.18) 9 (81.82) | 22 (56.41) 17 (43.59) | 0.03* |
RVOT obstruction Mean (SD) Median (range) | 33.09 (17.66) 27 (15 - 62) | 19.74 (7.28) 19 (6 - 35) | 0.02* |
RVOT obstruction <25 ≥25 | 5 (45.45) 6 (54.55) | 28 (71.79) 11 (28.21) | 0.10 |
PASP Mean (SD) Median (range) | 61.18 (18.27) 62 (38 - 93) | 43.51 (10.71) 43 (25 - 78) | 0.001* |
Characteristics | Dilated | Not dilated | p value |
---|---|---|---|
aortic annulus Mean (SD) Median (range) | 25.36 (3.04) 26 (19 - 29) | 19.41 (3.68) 18 (13 - 26) | 0.0001* |
Z score Mean (SD) Median (range) | 3.91 (0.30) 4.01 (3.49 - 4.45) | 1.73 (0.83) 1.93 (0.08 - 2.87) | <0.0001* |
STJ Mean (SD) Median (range) | 27.82 (3.49) 28 (21 - 33) | 21.59 (3.99) 20 (14 - 28) | 0.0002* |
Z score Mean (SD) Median (range) | 3 (0.23) 2.98 (2.74 - 3.57) | 1.46 (0.69) 1.7 (0.11 - 2.4) | <0.0001* |
Sinus of Valsalva Mean (SD) Median (range) | 36.81 (4.47) 37 (27 - 42) | 28.26 (5.16) 27 (18 - 38) | 0.0001* |
Z score Mean (SD) Median (range) | 4.18 (0.35) 4.13 (3.63 - 4.98) | 2.21 (0.69) 2.35 (0.4 - 3) | <0.0001* |
MAPCS/PDA No + | 11 (100.00) 0 (0.00) | 39 (100.00) 0 (0.00) |
& 29.5 (7 - 68) kg (
Characteristics | No. (%) |
---|---|
Age <96 months ≥96 months | 28 (56.00) 22 (44.00) |
Sex Female Male | 15 (30.00) 35 (70.00) |
Height Mean (SD) Median (range) | 123.51 (30.87) 126.5 (61 - 168) |
Weight Mean (SD) Median (range) | 34.17 (18.41) 29.5 (7 - 68) |
Characteristics | No. (%) |
---|---|
Arch side Left Right | 36 (72.00) 14 (28.00) |
Tab association No DORV and pulmonary atresia Down syndrome | 24 (24.00) 23 (46.00) 1 (2.00) |
Characteristics | No. (%) |
---|---|
BSA (m2) Mean (SD) Median (range) | 1.05 (0.42) 1.01 (0.32 - 1.77) |
O2 saturation % Mean (SD) Median (range) | 75.46 (9.13) 76 (48 - 95) |
O2 saturation % <80 ≥80 | 30 (60.00) 20 (40.00) |
root dilation was present in 70% (no = 35 pt) of unrepaired TOF while 30% (no = 15 pt) their aortic roots were not dilated. Our unrepaired Tetralogy of Fallot cases were further divided into two subgroups as regard presence of aortic root dilatation defined as aortic root Z score >3 at the level of aortic annulus, sinus of Valsalva & >2.5 at the level of STJ (
Characteristics | No. (%) |
---|---|
LVEF% Mean (SD) Median (range) | 59.3 (4.86) 60 (48 - 71) |
Aortic Regurgitation No Yes | 41 (82.00) 9 (18.00) |
Pulmonary Regurgitation No Yes | 49 (98.00) 1 (2.00) |
RVOT obstruction Mean (SD) Median (range) | 59.16 (19.50) 62.5 (25 - 91) |
RVOT obstruction <25 mmhg ≥25 mmhg | 0 (0.00) 50 (100.00) |
PASP (mmhg) Mean (SD) Median (range) | 32.68 (15.35) 27 (14 - 72) |
Aortic override <50 ≥50 | 29 (58.00) 21 (42.00) |
Characteristics | No. (%) |
---|---|
aortic annulus Mean (SD) Median (range) | 21.2 (6.40) 23 (9 - 35) |
Z score Mean (SD) Median (range) | 3.06 (1.60) 3.37 (0.33 - 6.26) |
STJ Mean (SD) Median (range) | 23.4 (7.03) 25.5 (10 - 40) |
Z score Mean (SD) Median (range) | 2.78 (2.89) 2.74 (0.19 - 21) |
Sinus of valsalva Mean (SD) Median (range) | 31.34 (8.31) 34 (14 - 45) |
Z score Mean (SD) Median (range) | 3.63 (1.17) 3.97 (0.99 - 5.66) |
MAPCS/PDA No + | 26 (52.00) 24 (48.00) |
Conclusion Dilated Not dilated | 35 (70.00) 15 (30.00) |
dilated groups was 1.24 (0.36) 1.26 (0.51 - 1.77) & 0.61 (0.17) & 0.61 (0.32 - 0.85) m2 respectively. The mean & median O2 saturation among dilated group was 72.97 (9.78) & 73 (48 - 95)% and 81.27 (2.74) & 81 (76 - 86)% among non dilated unrepaired TOF subgroup. Systemic arterial desaturation < 80% was measured in 77.14% (no = 27 pt) among the dilated group while 20% (no = 3 pt) among the non dilated subgroup. This reflects a significant statistical correlation between systemic arterial desaturation < 80% and aortic root dilation in unrepaired TOF (p value < 0.0001) (
Characteristics | Dilated | Not dilated | p value |
---|---|---|---|
Age <96 months >96 months | 22 (62.86) 13 (37.14) | 6 (40.00) 9 (60.00) | 0.14 |
Sex Female Male | 5 (14.29) 30 (85.71) | 10 (66.67) 5 (33.33) | <0.0001* |
Height Mean (SD) Median (range) | 137.93 (23.53) 146 (83 - 168) | 89.87 (16.06) 93 (61 - 110) | |
Weight (kg) Mean (SD) Median (range) | 41.89 (16.45) 42 (12 - 68) | 16.17 (5.67) 15 (7 - 26) |
Characteristics | Dilated | Not dilated | p value |
---|---|---|---|
Arch side Left Right | 22 (62.86) 13 (37.14) | 14 (93.33) 1 (6.67) | 0.03* |
Tab association No DORV & pulmonary atresia Down syndrome | 13 (35.14) 23 (62.16) 1 (2.70) | 15 (100.00) 0 (0.00) 0 (0.00) | <0.0001* |
Characteristics | Dilated | Not dilated | p value |
---|---|---|---|
BSA (m2) Mean (SD) Median (range) | 1.24 (0.36) 1.26 (0.51 - 1.77) | 0.61 (0.17) 0.61 (0.32 - 0.85) | |
O2 saturation % Mean (SD) Median (range) | 72.97 (9.78) 73 (48 - 95) | 81.27 (2.74) 81 (76 - 86) | 0.0004* |
O2 saturation % <80 ≥80 | 27 (77.14) 8 (22.86) | 3 (20.00) 12 (80.00) | <0.0001* |
Characteristics | Dilated | Not dilated | p value |
---|---|---|---|
LVEF% Mean (SD) Median (range) | 58.43 (5.28) 59 (48 - 71) | 61.33 (2.94) 61 (55 - 66) | 0.04* |
Aortic Regurgitation No Yes | 26 (74.29) 9 (25.71) | 15 (100.00) 0 (0.00) | 0.03* |
Pulmonary Regurgitation No Yes | 34 (97.14) 1 (2.86) | 15 (100.00) 0 (0.00) | 0.51 |
RVOT obstruction Mean (SD) Median (range) | 66 (17.78) 69 (28 - 91) | 43.2 (13.14) 40 (25 - 66) | 0.0001* |
RVOT obstruction <25mmhg ≥25mmhg | 0 (0.00) 35 (100.00) | 0 (0.00) 15 (100.00) | 0.02* |
PASP(mmhg) Mean (SD) Median (range) | 27.8 (13.68) 24 (14 - 72) | 44.07 (13.09) 39 (26 - 64) | 0.0001* |
Aortic override <50 ≥50 | 15 (42.86) 20 (57.14) | 14 (93.33) 1 (6.67) | 0.001* |
group compared to 44.07 (13.09) & 39 (26 - 64) mmHg in the non dilated group with (p value < 0.0001) (
The current study is an observational study to assess the relationship between clinical characteristics of patients with TOF including age and other variables with aortic root dilatation. Measurements of the aorta were made at the annulus, sinuses and sinotubular junction (STJ) converted to z-scores based on body surface area.
Surgeries for TOF have increasingly included intervention on the ascending aorta [
Characteristics | Dilated | Not dilated | p value |
---|---|---|---|
Aortic annulus Mean (SD) Median (range) | 24.63 (3.99) 25 (15 - 35) | 13.2 (2.62) 13 (9 - 17) | <0.0001* |
Z score Mean (SD) Median (range) | 3.97 (0.85) 3.71 (3.03 - 6.26) | 0.93 (0.51) 0.7 (0.33 - 1.68) | <0.0001* |
STJ Mean (SD) Median (range) | 27.2 (4.26) 27 (17 - 40) | 14.53 (2.90) 14 (10 - 19) | <0.0001* |
Z score Mean (SD) Median (range) | 3.09 (0.62) 2.8 (2.56 - 5.04) | 2.07 (5.26) 0.7 (0.19 - 21) | <0.0001* |
Sinus of valsalva Mean (SD) Median (range) | 35.97 (4.59) 36 (24 - 45) | 20.53 (3.40) 21 (14 - 25) | <0.0001* |
Z score Mean (SD) Median (range) | 4.31 (0.59) 4.3 (3.24 - 5.66) | 2.04 (0.38) 2.02 (0.99 - 2.46) | <0.0001* |
MAPCS/PDA No + | 16 (45.71) 19 (54.29) | 15 (100.00) 0 (0.00) | <0.0001* |
cause aortic root dilatation in adults with a repaired TOF (2). Another causative mechanism for progressive aortic root dilatation is marked histological abnormalities in the aortic root and ascending aortic wall [
The first case report of progressive ascending aortic dilation in patients with TOF was published in early 1970s [
The principal limitation of this study is its small sample size. Large number of patients is required to determine the extent of this problem and its correlation with various clinical entities with longer period of observation in future studies. The second limitation is that data on aortic root size before and early after TOF repair were not available. Thirdly, the echo studies were performed by different echocardiographers; therefore, inter- and intra-observer variability could not be assessed. In addition, 22q11 mutation status was not assessed in this cohort. Lastly, as patients with a dilated aorta were more likely to be followed up often, it is possible that the study suffers from ascertainment bias. This effect may be partly responsible for the apparent significant increase in Z score over time.
Male sex, previous conduit repair of pulmonary artesia, right aortic arch, systemic arterial desaturation, older age at repair, longer shunt to repair interval, residual post operative VSD shunt, impaired LV systolic function, presence of aortic regurgitation, pulmonary regurgitation, severe right ventricular outflow tract obstruction, TOF with pulmonary atresia, aortic override greater than 50%, major aortopulmonary collaterals and/or PDA were independent risk factors for aortic root dilatation in Tetralogy of Fallot. These risk factors account for or may coexist with the higher incidence of aortic root dilatation encountered in subset of patients with TOF subjected to long-standing cyanosis and volume overload.
Khaled R. AbdEl Meguid,Hesham B.Mahmoud,Mostafa M.Mohammad, (2015) Predictors for Dilated Aorta in Repaired and Unrepaired Tetralogy of Fallot. World Journal of Cardiovascular Diseases,05,233-253. doi: 10.4236/wjcd.2015.58027