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J Thorac Cardiovasc Surg 2003;126:1753-1759
© 2003 The American Association for Thoracic Surgery

Surgery for congenital heart disease

Prevalence and predictors of neoaortic regurgitation after arterial switch operation for transposition of the great arteries

^a Pediatric Cardiology and Cardiac Surgery, University of Bologna, Bologna, Italy
^b Pediatric Cardiology and Cardiac Surgery, "Bambino Gesù" Hospital, Rome, Italy

Presented at the Fiftieth Annual Scientific Session of the American College of Cardiology, Orlando, Fla, March 2001.

Received for publication January 20, 2003; revisions received April 1, 2003; accepted for publication June 25, 2003.

^* Address for reprints: Roberto Formigari, MD, FACC, Policlinico S. Orsola, Cardiologia e Cardiochirurgia Pediatrica, Via Massarenti 9, 40138 Bologna, Italy
r.formigari{at}mclink.it

	Abstract

Top Abstract Patients and methods Results Discussion Conclusions References

 
BACKGROUND: The fate of the native pulmonary valve after arterial switch operation is still unknown and may become a cause for a secondary aortic valve operation during adult life. We evaluated the prevalence and predictive factors associated with neoaortic valvular regurgitation by a retrospective study of children who underwent arterial switch operation for transposition of the great arteries.

METHODS: The onset of neoaortic valvular regurgitation was correlated with demographic data, cardiac anatomy, surgical technique, and postoperative ventricular function. The size of the neoaortic root and ascending aorta was measured in a selected subset of patients.

RESULTS: Among 253 survivors, 173 were eligible for the study. After a median follow-up time of 8.2 years, 61 patients showed echocardiographic or angiographic evidence of valvular incompetence, which was progressive in 14 cases; this led to surgical intervention in 2 patients, and there was 1 operative death. At multivariate analysis, the onset of valvular regurgitation was correlated with the trap-door technique for coronary reimplantation (P < .01). A smooth transition from the aortic sinus to the ascending aorta, with loss of the normal sinotubular junction geometry, may be associated with valvular incompetence.

CONCLUSIONS: After arterial switch operation, there is an increasing frequency of neoaortic regurgitation, which may lead to significant valvular dysfunction later in life. The trap-door type of coronary reimplantation is associated with an increased risk for valvular dysfunction, possibly because of a distortion of the sinotubular junction geometry. For this reason, we recommend the punch technique for repair in all but the most complicated coronary pattern.

	Patients and methods

Top Abstract Patients and methods Results Discussion Conclusions References

 
Patient population
Between January 1987 and January 2001, 288 patients underwent ASO at the 2 institutions involved in the study. The overall mortality was 12.1% over the entire 14-year experience. Cumulative mortality decreased to 6.3% during the last 5 years (1996-2001) and to less than 2% in the last 2 years. Of the 253 patients who survived the operation, 173 had complete and reliable follow-up records and form the study population.

Surgical technique
Moderately hypothermic extracorporeal circulation at 24°C was the preferred method of perfusion at both institutions. Circulatory arrest with selective cannulation of the innominate artery and low-flow cerebral perfusion at 20°C was usually performed if an aortic arch operation was needed. The Lecompte maneuver was performed with generous dissection of the pulmonary arteries. The coronary arteries were dissected free, and small collateral branches were sacrificed if they were suspected to cause distortion of the anastomoses. Two different strategies for coronary reimplantation were adopted: (1) the creation of 2.7-mm holes within the aortic wall and relocation of the coronary buttons proximal to the sinotubular junction (STJ; punch technique; 51% of the study population) or (2) the creation of a medially based trap-door flap rotated to open a space for coronary reimplantation (trap-door technique; 49% of the study population) without tissue excision from the proximal neoaorta. Patient selection in respect to the coronary relocation technique was different between the 2 institutions involved in the study. In one institution, the punch technique has been the method of choice since 1995, and the trap-door technique was limited to the patients operated on before 1995 or those with a single coronary orifice or an intramural course. In the other institution, the trap-door technique has been most often applied throughout their experience regardless of the coronary artery anatomy. The pulmonary trunk was always repaired with a pantaloon-shaped patch of autologous pericardium. An additional operation (besides ventricular septal defect [VSD] patch closure, pulmonary artery debanding, or both) was needed in 14 patients (aortic coarctation repair in 8, resection of the infundibular septum in 4, pulmonary artery plasty in 1, and mitral valve cleft repair in 1).

Follow-up protocol
Routine clinical and echocardiographic evaluation was performed 3 months after the operation and yearly thereafter in both centers. The echocardiographic assessment was performed with Hewlett-Packard Sonos 2500 (Hewlett-Packard, Palo Alto, Calif) and Agilent 5500 (Agilent Technologies, Palo Alto, Calif) models. Control cardiac catheterization and angiography in all patients who have undergone ASO between 1 and 3 years after the operation or earlier in case of branch pulmonary artery stenosis or residual defects has been the policy adopted by the 2 institutions since the beginning of the experience with anatomic repair of transposition. Overall, 152 patients had invasive postoperative studies at 4.0 ± 3.2 years (mean ± SD) after the operation. The remaining 21 patients either refused control cardiac catheterization or are currently waiting for it.

Data analysis
The clinical records were retrospectively reviewed to detect the onset, severity, and progression of valvular regurgitation or ventricular dysfunction. A review of previously recorded VHS tapes was needed in 47 patients to clarify the time of onset and severity of NeoAR or to assess left ventricular ejection fraction at the latest follow-up (calculated by the Teicholz, biplane area length, or Bullet method). The selection criterion was the presence of NeoAR, regardless of the magnitude of valvular incompetence. Valve incompetence was graded according to the scale of Galassi and associates.⁹ An ejection fraction value of less than 50% was considered suggestive of poor left ventricular performance. The surgical records were reviewed in regard to cardiac anatomy, coronary pattern, presence of bicuspid pulmonary valve, and other variables, eg, weight at operation and type of surgical technique. Among the variety of coronary patterns, usually described by either the Leiden or the Yacoub classification, a dichotomous variable was created to simplify the multivariate analysis: a complicated coronary pattern (single coronary orifice, or with intramural course) versus a simple one (all others).

Angiographic studies, when available, were reviewed for confirmation of the echocardiographic findings concerning the degree of regurgitation (if present) and ventricular function. Valve regurgitation was classified as trivial, mild, moderate, or severe.¹⁰ In 131 cases, the quality of the angiographic pictures allowed the assessment of the dimensions of the neoaortic valve, the sinuses of Valsalva, the STJ, and the ascending aorta, as described by Kunzelman and colleagues¹¹ (Figure 1), by using offline analysis (Osiris Imaging Software 3.6; University of Geneva, Geneva, Switzerland) of the frontal or right anterior oblique aortograms. The morphometric study was performed nonblinded by the authors (R.F., A.G., and A.T.), and the remaining 20 patients were excluded because of the poor quality of their angiographic imaging. All values were normalized to the size of the descending aorta well beyond the isthmus. Furthermore, measurement of the distance between the STJ, the sinus, and the plane of the semilunar valves (Figure 1) was attempted in an additional small subgroup of cases (7 patients) with late-onset NeoAR (more than 2 years after ASO) and with digitally stored optimal angiographic images. These were compared with the results obtained from the same calculations made on postoperative angiograms of 17 children without NeoAR.

View larger version (45K): [in this window] [in a new window]   Figure 1. Morphometric assessment of the neoaorta after arterial switch operation. The measurements were taken at the level of the ascending aorta (D), sinotubular junction (C), neoaortic sinus (B), and semilunar leaflets (A). The height of the sinotubular junction was measured as E1 and E2. All values were normalized against the measurement of the normal descending aorta (F).

	Results

Top Abstract Patients and methods Results Discussion Conclusions References

 
The median age at ASO was 8 days (range, 2-344 days). One hundred thirty-six patients had transposition with intact ventricular septum, 33 had transposition with VSD (TGA-VSD), and 4 had a double-outlet right ventricle with subpulmonary VSD. In 8 patients, the repair was staged by preliminary pulmonary artery banding. The median follow-up time was 8.2 years (range, 0.6-11.2 years).

Sixty-one patients (35%) had Doppler or angiographic evidence of NeoAR. The Kaplan-Meier plot for freedom from postoperative valvular incompetence is shown in Figure 2. No surgical period could be isolated during the entire experience (Figure 3). Eleven patients (18% of the NeoAR group) had trivial to mild valvular incompetence during the early postoperative phase. In one patient, a progressive valvular dysfunction was noted at 10 years of age, whereas all the others were free from NeoAR at discharge and developed regurgitation between 2 and 5 years after the operation.

View larger version (16K): [in this window] [in a new window]   Figure 2. Cumulative freedom from neoaortic regurgitation after arterial switch operation. ASO, Arterial switch operation. The numbers at risk are shown above the x-axis.

View larger version (22K): [in this window] [in a new window]   Figure 3. Time distribution of NeoAR from 1987 to 2000. The numbers above the bars show the yearly prevalence of NeoAR.

Year of operation
The year of operation had no significant effect on the regression model (P = .13; RR, 0.98; 95% CI, 0.96-1.31).

Previous palliation
NeoAR was recognized in 1 of the 8 patients who had 2-stage ASO (12.5%), versus 60 in the group with primary repair (36.3%), with no difference by univariate or multivariate analysis (RR, 2.3; 95% CI, 0.78-8.30).

Ventricular function
Ventricular function was mildly depressed in 2 patients with a normal neoaortic valve, versus 1 in the NeoAR group, without statistical significance by univariate analysis.

Ventricular anatomy
A large VSD or a Taussig-Bing anatomy was a common finding in the NeoAR group, whereas an intact septum was more frequent within the group with a competent neoaortic valve. However, the multivariate study showed that the difference between the 2 groups could be due to chance (P = .18; RR, 1.5; 95% CI, 0.82-2.76).

Coronary anatomy
Complicated coronary patterns were more common in the group without NeoAR, but this difference could be due to chance (P > .2).

Coronary relocation technique
Coronary reimplantation by trap-door technique was a frequent finding among patients with NeoAR (68.8% vs 30.1% in the control group), as confirmed by the univariate study. This finding was even more important after multivariate analysis, which showed the trap-door technique as a strong predictive factor for the onset of NeoAR (RR, 3.48; 95% CI, 1.91-6.36).

Bicuspid valve
A bicuspid pulmonary valve was found in only 5 cases and was not correlated with the onset of NeoAR (RR, 1.46; 95% CI, 0.34-6.16).

Aortic interruption or coarctation and left ventricular outflow tract obstruction
The univariate analysis showed no correlation between neoaortic valvular function and surgical repair of interruption or coarctation of the aortic arch or preoperative evidence of mild left ventricular outflow tract obstruction.

Morphometric analysis
Among the patients with available morphometric analysis, 59 had NeoAR, and 72 had a competent semilunar valve. There were no differences between the 2 groups in the widths of single segments of the neoaortic root. However, the ratio between the diameter of the sinotubular ridge and the maximum diameter of the neoaortic sinus was higher in the patients with NeoAR than in the control group (Table 3). The graphical reconstruction of the neoaortic root, based on diameters measured on the angiographic pictures, shows that the patients with NeoAR usually have an elongated neoaortic root with a smooth transition from the sinus to the ascending aorta and a flattened STJ (Figures 4 and 5). Moreover, the STJ seems displaced, with an increased distance from the sinuses of Valsalva (Table 3 and Figure 5).

View larger version (72K): [in this window] [in a new window]   Figure 4. Postoperative angiograms of the neoaorta showing a typical case of late-onset neoaortic regurgitation (A) and another one with a perfectly competent systemic semilunar valve (B). Note the smooth and elongated shape of the case in panel A in contrast to the well-defined sinotubular junction of the patient depicted in panel B. AAo, Ascending aorta; LV, left ventricle.

View larger version (124K): [in this window] [in a new window]   Figure 5. Shape of the neoaortic root of the patients with and without NeoAR. The normal human aortic root (modified from Kunzelman and colleagues11) is shown for comparison. The sinus diameter is represented by a value of 1, and all other values are represented by a fraction of this number. The figures are not in scale and are meant only to give information about the shape of the root.

	Discussion

Top Abstract Patients and methods Results Discussion Conclusions References

The 2 variables expected to play a role in the development of NeoAR—ie, previous pulmonary artery banding^14,15 and the presence of bicuspid pulmonary valve¹⁶—did not reach statistical significance in our series. However, the small number of patients with a 2-stage repair and the surprisingly low incidence of bicuspid pulmonary valve in our population may account for this lack of correlation. However, although the issue of pulmonary artery banding is further restricted to a few selected patients undergoing 2-stage ASO, the presence of a bicuspid native pulmonary valve should prompt some caution, at least according to studies on the natural history of the bicuspid aortic valve.¹⁶

These data do not clarify whether progressive dilatation of the neoaortic root may cause failure of leaflet coaptation, as suggested by Marino and associates.¹⁷ In fact, we found no correlation between NeoAR and absolute sizes of the neoaortic root segments. This piece of evidence led us to speculate that the late onset of aortic regurgitation may be induced, instead, by a complex rearrangement of the STJ geometry, and the differences we found in the height of the STJ and in the STJ/sinus ratio seem to support this hypothesis. The graphical reconstruction of the neoaortic root in post-ASO patients with and without NeoAR compared with the geometry of a normal aorta as described by Kunzelman and colleagues¹¹ possibly explains how subtle morphofunctional differences between the 2 groups of our series may affect the delicate ergonomic interaction and permit coalescence of the 3 aortic cusps. In fact, there is a proven role of the 3-dimensional anatomy of the aortic root in healthy subjects versus that in patients with chronic aortic regurgitation,^18-21 and this role is indirectly substantiated by the success of valve-sparing surgical techniques by David and Feindel,²² although their study was in adult patients. Unfortunately, we were not able to track the variation of root dimensions because of the lack of precise echocardiographic measurements in all patients across the entire experience; this limited our capability to provide a more comprehensive analysis of the potential interrelations between coronary reimplantation techniques and aortic morphology.

The reason why NeoAR seems to appear with increasing frequency 2 to 4 years after the operation in subjects with an otherwise perfectly functional postoperative neoaortic valve is still unclear. Although other studies concerning the size and growth of the neoaortic root and anastomosis have been published,^22-24 the simple measurement of the diameter of the vascular structures may be insufficient to outline the complex geometric modifications of the growing neoaortic root after ASO. Indeed, the late occurrence of NeoAR in many patients and the results of the morphometric study suggest that the neoaortic root distortion should not be regarded as the result of a direct surgical injury but rather as an effect of some degree of growth impairment, which is possibly magnified by the extensive remodeling caused by the opening of the trapdoors. Furthermore, we cannot rule out a role of the discrepancy in caliber between the native aortic and pulmonary roots, eg, in the cases with TGA-VSD and aortic coarctation.

This was a retrospective study and shares all the limitations of similar inquiries. Potential criticism may also be stimulated by the risk of underestimating time-related factors concerning the surgical technique. In this case, the trap-door coronary reimplantation could have been associated with the initial ASO experience; thus, it would be correlated with the learning curve for this operation rather than being an independent variable (an alfa-zero error). However, both types of coronary techniques (trap-door and punch reimplantation) were evenly distributed across the entire experience, thus limiting the potential effect of the learning curve. Other interesting variables were not included in this study for lack of reliable retrospective information. Among these, the relative size and spatial relationship of the native pulmonary and aortic valve would have been significant and deserve further consideration. Moreover, the morphometric study may have been influenced by the nonblinded measurements performed by the authors. A mild overestimation of the NeoAR prevalence should also be taken into account, because we cannot exclude the presence of cases with a native incompetent pulmonary valve that may have gone undetected or simply unreported in the preoperative study, thus unrelated with any type of surgical procedure. However, because the number of patients with valvular regurgitation at discharge was limited (18% of the NeoAR group), this should be only a minor issue.

	Conclusions

Top Abstract Patients and methods Results Discussion Conclusions References

 
In conclusion, NeoAR is probably the result of a multifactorial process for which STJ geometry and surgical technique are some of the mechanisms involved. Even if increasing in incidence over time, NeoAR is often a stable condition, at least during the first 10 years. The trap-door type of coronary reimplantation is associated with an increased risk for NeoAR. Therefore, we endorse this option for coronary reimplantation only in those cases with the most complicated coronary patterns.

	References

Top Abstract Patients and methods Results Discussion Conclusions References

 

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