Using noninvasive techniques, we sought to assess arterial stiffness, impedance, hydraulic power, and efficiency in children with postoperative tetralogy of Fallot (TOF), coarctation of the aorta (COA), and transposition of the great arteries (TGAs). Results were compared with those of healthy peers. Fifty-five children with repaired congenital heart disease (24 TOFs, 20 COAs, and 11 TGAs) were compared with 55 age-matched control subjects (CTRL). Echocardiographic Doppler imaging and carotid artery applanation tonometry were preformed to measure aortic flow, dimensions, and calculate pulse wave velocity, vascular impedance and arterial stiffness indexes, hydraulic power (mean and total), and hydraulic efficiency (HE) which were calculated using standard fluid dynamics equations. All congenital heart disease subgroups had higher pulse wave velocity than CTRL. Only the COA group had higher characteristic impedance. Mean power was higher in TGA than in CTRL and TOF, and total power was higher in TGA than in CTRL and TOF. Hydraulic efficiency was higher in TOF than in COA and TGA. In conclusion, children with TOF, COA, and TGA have stiffer aortas than CTRL. These changes may be related to intrinsic aortic abnormalities, altered integrity of the aorta due to surgical repair, and/or acquired postsurgery. These patients may be at increased long-term cardiovascular risk, and long-term follow-up is important for monitoring and assessment of efforts to reduce risk.
The improved survival of patients with postoperative congenital heart disease (CHD) has created a population at increased cardiovascular risk. We have previously described an echocardiographic technique to measure the biophysical properties of the aorta, including pulse wave velocity (PWV), arterial stiffness (elastic pressure-strain modulus [Ep] and stiffness indexes [β-index]), input [Zi], and characteristic impedances [Zc]. The total power (W t ), mean power (Wm), oscillating power (Wo) and hydraulic efficiency (HE) generated by the systemic ventricle in a pulsatile flow model can be determined using simultaneous recording of carotid pulse pressure by applanation tonometry and Doppler ascending aorta flow with a hydraulic theory model. The objective of this noninvasive study was to determine if patients with transposition of the great arteries (TGA), TOF, and coarctation of the aorta (COA) have abnormal vascular properties and HE.
Methods
This was a clinical cohort study. All patients aged older than 8 years with TOF, COA or TGA who were having their regular follow-up visit at British Columbia Children’s Hospital during a 1-year period were asked to participate in this study. Fifty-five children were enrolled. Demographics and physical characteristics of each group of patients are presented in Table 1 . The control group comprised 55 age-matched healthy children, all with normal results on cardiac examination and on echocardiography, selected from our data pool of volunteers or clinic patients.
| Variable | CTRL | TOF | COA | TGA | p |
|---|---|---|---|---|---|
| Male:Female | 31:24 | 14:10 | 11:9 | 6:5 | – |
| Age at study [yr] | 14.1 (12.5-17.6) | 15.2 (13.3-16.8) | 13.4 (11.7-16.6) | 14.3(12.8-16.0) | NS (0.76) |
| Weight [kg] | 53.6 (45.1-64.0) | 55.1 (41.0-63.4) | 53.8 (44.0-66.4) | 53.8 (41.3-68.9) | NS (.99) |
| Height [cm] | 163.5 (154.0-171.0) | 162.6 (154.6-171.7) | 163.6 (150.5-168.7) | 164.0 (156-172.6) | NS (0.72) |
| Body surface area [m 2 ] | 1.58 (1.43-1.73) | 1.57 (1.34-1.75) | 1.54 (1.36-1.84) | 1.56 (1.36-1.77) | NS (0.98) |
| Body mass index [kg/m 2 ] | 20.2 (18.3-22.3) | 20.4 (17.9-21.9) | 20.0 (18.6-23.1) | 19.5 (17.0-23.6) | NS (0.80) |
| Systolic pressure [mmHg] | 112 (104-117) | 110 (101-114) | 112 (106-124) | 116 (105-118) | NS (0.20) |
| Diastolic pressure [mmHg] | 65 (60-73) | 64 (60-70) | 62 (60-70) | 62 (55-70) | NS (0.49) |
| Heart rate [bpm] | 66 (58-75) | 75 (67-83) ∗ | 67 (57-75) | 57 (52-65) ∗ | 0.016 |
∗ Legend for significant results based on post hoc Mann–Whitney U test is TOF versus TGA.
Standard 2-dimensional, M-mode, and Doppler echocardiography was performed on all patients. The ventricular ejection fraction was calculated from end-systolic and end-diastolic volumes estimated using a Simpson’s rule algorithm. The left ventricular outflow tract (LVOT) diameter was measured at the valve leaflets in systole from the parasternal long-axis view. The aortic flow was calculated from the pulse wave Doppler waveform sampled in the apical 5-chamber view. The techniques that we used to measure PWV, arterial stiffness, and impedance have been described previously ( Appendix A ). From the standard suprasternal long-axis view of the aortic arch, pulse wave Doppler waveforms were obtained in the ascending and descending aorta, respectively and on-line calipers were used to measure the length of the aortic arch. An M-mode recording of the ascending aorta was obtained from the high suprasternal view and the diameter measured at end-diastolic and maximum systolic dimensions. For the measurement of indexes derived from hydraulic power and total arterial compliance, carotid pressure waveforms were recorded with applanation tonometry using a Millar pulse transducer (Model SPT-301; Millar Instruments, Inc., Houston, Texas) connected through a control box (model SD-640; Millar Instruments, Inc.) to a GE Vivid 7 Pro ultrasound machine (GE Healthcare, Wauwatosa, Wisconsin). The carotid pressure waveforms were obtained simultaneously with pulse wave Doppler waveforms in the ascending aorta and sphygmomanometric measurement of the left brachial artery blood pressure in the supine position. Three pressure waveforms were selected and averaged. In calibrating the tonometry pressure, diastolic and mean pressures were assumed to be the same at the carotid artery and at the brachial artery. Fourier analysis of the pressure and flow data derived from the aortic and carotid waveforms was used to calculate LV hydraulic power as previously described ( Appendix A ). It was assumed that mean and diastolic arterial brachial blood pressure remained constant throughout the large arterial tree. The aortic flow waveform was calculated by multiplying the aortic blood velocity spectrum envelope by the LVOT cross-sectional area calculated from the LVOT annular diameter, assuming a circular orifice. Since the pressure and flow waves were recorded at different locations, there was a time lag between them. This was corrected by aligning the foot of the pressure wave to the onset of flow.
Calculation of the sample size was based on our primary outcome measure, PWV. On the basis of previous studies, an increase of 50 cm/s was considered abnormal. A planned enrollment of 20 patients for each CHD cohort was estimated to provide 90% power, with a 2-sided α level of 0.05, to detect a 50 cm/s difference between groups. Contingency tables were generated for all categorical variables. Univariate analyses were performed on all continuous variables. Medians and the interquartile range are presented. A Kruskal–Wallis 1-way analysis of variance was used to determine differences between groups. Post hoc comparisons were performed using a Mann–Whitney U test. All tests were 2-sided with a p <0.05 considered statistically significant. All statistical analyses were performed using SPSS software, version 21 (IBM Corporation, Armonk, New York). The study protocol was approved by the University of British Columbia’s Clinical Research Ethics Board and the Children’s and Women’s Health Centre of British Columbia’s Research Review Committee.
Results
The demographic and clinical characteristics of the different groups are presented in Table 1 . The only significant difference between them is a slightly slower heart rate for TGA compared with tetralogy of Fallot (TOF) patients. The characteristics of patients with CHD, including age at initial surgery, type of surgery, additional lesions present at time of the study, and chromosomal abnormalities, are presented in Table 2 . One patient with COA was receiving a beta blocker and 1 patient with TGA, an angiotensin-converting enzyme inhibitor. Other medications including furosemide, digoxin, aspirin, coumadin, a bronchodilator, and an antiepileptic were prescribed in 6 patients.
| Coarctation patients | 20 |
| Age at surgery [month(median)] | 2.0 (0.2-5.1) |
| Type of correction | |
| End to end | 10 (50%) |
| Subclavian flap | 6 (30%) |
| Patch (gore-tex, contegra) | 1 (5%) |
| Interposition graft | 1 (5%) |
| Balloon angioplasty | 1 (5%) |
| No intervention | 1 (5%) |
| Additional lesions | |
| Bicuspid aortic valve | 7 (35%) |
| Shone complex | 6 (30%) |
| Residual coarctation ∗ | 2 (10%) |
| Others † | 4 (20%) |
| Tetralogy of Fallot patients | 24 |
| Age at surgery [month(median)] | 10.4 (6.4-35.0) |
| Type of surgery | |
| RV-PA conduct | 9 (38%) |
| RV and/or PA patch | 7 (29%) |
| Transvalvular patch | 5 (21%) |
| Pulmonary valve valvotomy | 2 (8%) |
| Unknown | 1 (4%) |
| Additional lesions ‡ | |
| Residual main or peripheral pulmonary stenosis § | 4 (17%) |
| Complete atrioventricular block with pacemaker implanted | 4 (17%) |
| Residual ventricular septal defect | 2 (8%) |
| >Mild tricuspid regurgitation | 2 (8%) |
| >Mild pulmonary regurgitation | 1 (4%) |
| Chromosomal abnormalities | |
| 22q11 microdeletion | 4 (17%) |
| Down syndrome | 1 (4%) |
| Transposition of the great arteries patients | 11 |
| Age at surgery [day(median)] | 12.0 (10.5-19.5) |
| Type of surgery | |
| Arterial switch | 11 (100%) |
| Additional lesions | |
| Ventricular septal defect | 1 (4%) |
| Supraortic obstruction | 1 (4%) |
| Peripheral PA stenosis | 1 (4%) |
| Right coronary stenosis | 1 (4%) |
| Complete AVB, pacemaker | 1 (4%) |
∗ Residual differential peak gradient >20 mm Hg at echo.
† Includes residual VSD, aortic stenosis, aortic mechanical valve after Ross procedure, bicuspid aortic valve + LPA stenosis + residual COA.
‡ Several had multiple additional lesions.
Echocardiographic aortic and LV dimensions, function, and hemodynamics are presented in Table 3 . The COA group showed concentric LV hypertrophy with increased systolic function and mass. The TGA group had increased LV size with compensatory LV hypertrophy and mass but, interestingly, also higher wall stress. The TOF group showed reduced stroke volume indexed for body surface area. The size of the LV outflow tract and ascending aorta were different; TGA and TOF had larger dimensions, and COA was smaller than control subjects (CTRL). Peak aortic velocity was significantly higher in COA than in CTRL and TOF, and significantly higher in CTRL than in TGA. The biophysical properties of the aorta and HE results are presented in Table 4 . All CHD groups had higher values for PWV than for CRTL. Only TOF and COA patients had higher Zc. Patients with TGA had higher Wm and Wt than TOF and CTRL. There was no significant difference for HE between CTRL and CHD groups, but HE was higher for the TOF group compared with COA and TGA.
| CTRL | TOF | COA | TGA | p | |
|---|---|---|---|---|---|
| Interventricular septum dimension in diastole (cm) | 0.75 (0.64-0.84) | 0.79 (0.71-0.89) | 0.80 (0.70-1.07) | 0.80 (0.65-0.83) | NS (0.144) |
| Left ventricle end diastolic diameter (cm) | 4.7 (4.3-5.0) | 4.5 (3.9-5.0) ∗ † | 5.0 (4.5-5.3) ∗ | 5.1 (5.0-5.5) ‡ † | 0.002 |
| Left ventricle end systolic diameter (cm) | 2.9 (2.7-3.2) | 2.9 (2.6-3.5) † | 2.8 (2.5-3.1) § | 3.4 (3.3-3.6) ‡ § † | <0.001 |
| Posterior wall dimension in diastole (cm) | 0.72 (0.64-0.83) | 0.72 (0.64-0.80) | 0.76 (0.63-0.97) | 0.80 (0.63-0.84) | NS (0.89) |
| Posterior wall dimension in systole (cm) | 1.2 (1.1-1.3) | 1.2 (1.0-1.3) | 1.3 (1.0-1.5) | 1.2 (1.1-1.3) | NS (0.29) |
| Shortening fraction (%) | 37 (34-41) | 33 (31-39) ‡ ∗ | 41 (36-49) ‡ ∗ § | 34 (32-36) ‡ § | <0.001 |
| Left ventricle outflow tract cross sectional area (cm 2 ) | 2.84 (2.43-3.14) | 2.88 (2.58-3.59) ∗ | 2.27 (1.83-3.14) ‡ ∗ § | 3.33 (3.14-3.80) ‡ § | = 0.001 |
| Aortic root diameter at the sinus of Valsalva (cm) | 2.7 (2.4-2.8) ‡ | 3.3 (3.0-3.9) ‡ ∗ | 2.6 (2.3-2.8) ∗ § | 3.4 (2.8-3.6) ‡ § | <0.001 |
| Aortic root diameter at the sinotubular junction (cm) | 2.2 (2.0-2.3) | 2.6 (2.3-3.4) ‡ ∗ | 2.1 (1.8-2.3) ∗ | 2.4 (1.8-2.7) | <0.001 |
| Peak aortic velocity (cm/s) | 110 (100-125) | 100 (80-110) ‡ ∗ | 120 (110-140) ‡ ∗ § | 100 (80-110) ‡ § | <0.001 |
| Wall Stress at peak systole (dyne/cm 2 ) | 64 (54-74) | 60 (52-80) ‡ | 58 (46-76) § | 85 (69-102) § | 0.016 |
| Peak Aortic Flow (cm 3 /s) | 314 (265-377) | 284 (229-418) | 281 (241-346) | 346 (290-381) | NS (0.47) |
| Left ventricular mass index (g/m 2 ) | 87 (73-99) | 83 (68-101) ∗ | 106 (84-123) ‡ ∗ | 111 (82-119) ‡ † | 0.004 |
| Stroke volume index (L/m 2 ) | 40 (34-44) | 32 (28-39) ‡ ∗ † | 39 (34-49) ∗ | 45 (38-54) † | = 0.001 |
| Cardiac output index (L/min/m 2 ) | 2.55 (2.19-3.12) | 2.51 (1.99-2.95) | 2.63 (1.95-3.35) | 2.87 (2.45-3.04) | NS (0.76) |
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