Poor outcomes after surgery for coarctation repair with hypoplastic arch warrants more extensive initial surgery and close long-term follow-up

Abstract

OBJECTIVES

Late outcomes of repair of coarctation with arch hypoplasia have not yet been described. Hypertension and arch reobstruction frequently occur after standard coarctation repair and thus we sought to determine the long-term results of repair in the subset of patients with arch hypoplasia at a single institution over a 20-year period.

METHODS

We reviewed the files of the 305 consecutive patients quoted to have arch hypoplasia who had undergone a coarctation repair in a single institution between 1984 and 2004. Repair was performed through a sternotomy in 74 patients (24%), 58 of them undergoing a repair consisting of an end-to-side anastomosis.

RESULTS

Early mortality was 9% but there was only 1 death among patients without a major associated anomaly. Eight patients required reintervention before discharge due to residual obstruction. The follow-up was available in 96% of the patients. Only 45% of the patients over 15 years of age had cardiology review in the last 2 years. Survival at 10 and 20 years was 94% (95% CI: 91–97%) and 92% (95% CI: 86–95%), respectively. There were a total of 66 late reinterventions in 49 (18%) patients. Ten- and 20-year freedom from reintervention was 84% (95% CI: 78–88%) and 72% (95% CI: 63–80%), respectively. Ten- and 20-year freedom from reobstruction was 75% (95% CI: 69–80%) and 45% (95% CI: 34–55%), respectively. Patients undergoing end-to-side repair from sternotomy had less arch reobstruction than those undergoing extended end-to-end repair by thoracotomy (92 vs 61% freedom from reobstruction at 10 years, P < 0.001). Only 68% of the patients were normotensive at the last follow-up. Arch obstruction on echocardiogram was associated with an increased prevalence of hypertension (P = 0.018).

CONCLUSIONS

After coarctation repair, half of the patients with hypoplasia of the transverse arch will develop arch reobstruction and a third will become hypertensive. The technique of end-to-side repair performed through a sternotomy seems to alleviate these issues, and could be offered to a larger proportion of patients with hypoplasia of the aortic arch. Many of these patients are lost to follow-up during adolescence, at a time when ongoing care seems mandatory.

INTRODUCTION

For many years, it has been known that patients undergoing repair of aortic coarctation could become hypertensive at a young age, but their real risk of suffering hypertension is still largely unknown. In the early 1990s, the only study examining three decades of outcomes after coarctation repair revealed that up to 25% of patients could face mortality related to complications of hypertensive disease [1]. Because of the historical nature of this study, this alarming fact has been largely overlooked in the following two decades, because our community of cardiologists and cardiac surgeons estimated that the evolution beyond early operations and better surgical techniques should naturally decrease the incidence of residual or recurrent hypertension after coarctation repair. Recent reports have revived the fear that hypertension may be far more prevalent than initially thought in the young adults who have undergone coarctation repair [1–4]. The persistence or recurrence of hypertension after repair has been linked to later age at repair, the existence of residual obstruction, a suboptimal aortic arch shape and unclear neuro-humoral mechanisms initiated before repair [1, 4, 5]. We have recently investigated whether small transverse aortic arches grew harmoniously after repair. In a pilot study of 20 patients followed serially over the course of 15 years, we identified that up to a third of patients with small arches operated by thoracotomy had unsatisfactory growth of their proximal transverse arch and were at a risk of residual hypertension [6]. If it is confirmed that patients with small aortic arches are at a risk of residual obstruction, a larger proportion of them should undergo a more extensive repair via a sternotomy as it has been demonstrated that this approach is linked to a very low incidence of late hypertension [7].

We therefore decided to review our experience with coarctation repair in all patients with small aortic arches in order to determine the incidence of reintervention and hypertension late after repair.

PATIENTS AND METHODS

The design of the study was approved by the Royal Children's Hospital Human Research Ethics Committee, and the need for consent was waived because of the retrospective nature of the study.

Patients

We intended to collect the data on patients who would have been subjected to a homogenous form of treatment and who would have accumulated enough length of the follow-up, and therefore examined our hospital database for patients operated between 1984 and 2004. Over this period, 837 patients underwent a repair of coarctation of the aorta. The 305 patients who were quoted to have a small or hypoplastic arch in the echocardiographic, cardiological or surgical reports constitute the core population of this study. Patients' characteristics are displayed in Table 1.

Table 1:

Patient characteristics

Patient characteristics	Patients (%)
Male:female	189 (62):116 (38)
Median birth weight (kg)	3.2 (2.72–3.6)
Median age at operation (days)	11 (5–29)
Cardiac anomalies
Ventricular septal defect	176 (58)
Bicuspid aortic valve	125 (41)
Atrial septal defect	72 (24)
Borderline small left ventricle	36 (12)
Left ventricular outflow obstruction	35 (12)
Transposition of the great arteries	30 (10)
Atrioventricular septal defect	21 (7)
Double outlet right ventricle	17 (6)
Taussig–Bing anomaly	13 (4)
Anomalous right subclavian artery	10 (3)
Partial anomalous pulmonary drainage	5 (2)
Right aortic arch	1 (0)
Other cardiac anomalies	32 (11)
Associated syndromes
Turner syndrome	6 (2)
Shone syndrome	6 (2)
Down syndrome	5 (2)
William's syndrome	2 (1)

Preoperative echocardiogram tapes were available in 89 of 305 patients (29%). The proximal arch diameter was measured between the innominate and left common carotid artery, and the distal transverse arch was measured between the left common carotid and the left subclavian artery. Z-scores were calculated using Petterson's regression model [8].

Surgical procedures

The arch was repaired through a sternotomy in 74 patients (24%) and thoracotomy in 231 patients (76%). Fifty-eight (78%) of the 74 patients undergoing a sternotomy had an end-to-side arch repair (Fig. 1). Details of the operative techniques have been previously described [7, 9]. In end-to-side repair, ductal tissue was carefully resected before proceeding to the anastomosis.

Figure 1:

An end-to-side anastomosis.

Concomitant procedures were performed in 101 patients (33%). The operative data are shown in Table 2. Fifty-three patients required 61 additional separate cardiac operations during the hospital stay. There were 24 ventricular septal defect closures, 9 pulmonary artery bandings, 5 arterial switch operations and 23 other procedures.

Table 2:

Operative data

Surgical characteristics	Patients (%)
Surgical era
1984–1989	80 (26)
1990–1999	151 (50)
2000–2004	74 (24)
Arch repair technique
Sternotomy	74 (24)
End-to-side anastomosis	58 (78)
Extended end-to-end anastomosis	7 (10)
Patch repair	6 (8)
Subclavian flap repair	1 (1)
Miscellaneous arch repair	2 (3)
Thoracotomy	231 (76)
Subclavian flap repair	96 (42)
Extended end-to-end anastomosis	85 (37)
End-to-side anastomosis	19 (8)
End-to-end anastomosis	17 (7)
Patch repair	8 (4)
Miscellaneous arch repair	6 (3)
Associated cardiac procedures
Sternotomy	70/74 (95)
Ventricular septal defect closure	49 (66)
Atrial septal defect closure	25 (34)
Arterial switch operation	17 (23)
Pulmonary artery banding	11 (15)
Left ventricular outflow obstruction repair	10 (14)
Other	14 (19)
Thoracotomy	31/231 (13)
Pulmonary artery banding	29 (13)
Other	2 (1)
Intraoperative data
Median clamp time (min)	21 (7–272)
Median time on bypass (min)	134 (34–340)

Definitions

Early outcomes were those that occurred within 30 postoperative days or during the hospital stay. Late outcomes occurred after this period of time.

Patients who were not followed beyond the first year after surgery were considered lost to the follow-up.

Patients were considered to have reobstruction if they had clinical evidence of obstruction demonstrated by an arm-leg blood pressure gradient exceeding 20 mmHg, echocardiographic evidence of a gradient exceeding 25 mmHg across the repair site or if they required a reintervention for arch obstruction.

Patients were considered to be hypertensive if their systolic or diastolic blood pressure exceeded the 95th percentile, and pre-hypertensive if between the 90th and 95th percentile, for age, gender and height based on the Fourth Report on the Diagnosis, Evaluation and Treatment of High Blood Pressure in Children and Adolescents [10].

Statistical analysis

Data were exported to STATA 10 (Stata Corp, College Station, TX, USA). Continuous variables were expressed as the median with the interquartile range or as mean ± standard deviation. Preoperative, perioperative and follow-up variables were examined by the univariate analysis for the following binary outcomes: hospital mortality, early reintervention and hypertension. The impact of associated cardiac anomalies on hospital mortality was examined by classifying anomalies into groups. Simple anomalies included patients with no associated cardiac anomalies, atrial septal defect or bicuspid aortic valve. Patients with the isolated ventricular septal defect were examined separately from patients with anomalies, such as transposition of the great arteries, double outlet right ventricle or atrioventricular septal defect, which were classified as complex. Potential risk factors identified by a P-value < 0.1 on univariate analysis were entered into a stepwise multivariate logistic regression analysis. The Kaplan–Meier survival curves were drawn to examine long-term survival, reintervention and reobstruction. Survival data were expressed as survival percentage with 95% confidence interval. The impact of pre-operative and perioperative variables on time-related variables was examined by the univariate Cox regression analysis. Risk factors with a P-value < 0.1 were then entered into a stepwise multivariate analysis. A P-value of less than 0.05 was considered significant.

RESULTS

Early outcomes

Early mortality

Twenty-six patients (9%) died in the immediate postoperative period. The causes of death were low output syndrome (15), stroke (4), sepsis (3), respiratory failure (1) and unknown (3).

By the multivariate analysis, predictors of hospital mortality were birth weight less than 3 kg (P = 0.003), having a complex-associated cardiac anomaly (P = 0.031), and undergoing concomitant cardiac procedure (P = 0.047). Among patients with simple cardiac anatomy, early mortality was 1.3%. The ventricular septal defect group had an operative mortality of 4.3%. The mortality in the complex anomaly group was higher at 15.4% (P = 0.031). Nine of the 45 patients undergoing a one-stage repair (20%) and 12 of the 91 undergoing delayed repair (13.1%) died (P = 0.3).

Early reintervention

Eight patients (2.7%) required nine reinterventions on the aortic arch to relieve residual obstruction during the early postoperative period. This included seven reoperations and two balloon dilations. There were no reinterventions and no reported left main bronchus obstruction among the patients with end-to-side repair performed via sternotomy.

Late outcomes

Eleven of the 279 hospital survivors were lost to the follow-up so that the completeness of the follow-up was 96%. Of the 268 patients followed, 199 (71%) had a cardiology review in the last 2 years. Of 101 patients aged 15 years or older, only 45% had seen their cardiologist in the past 2 years. Adolescent and adult patients abandoning regular follow-up had been followed for a mean of 12 ± 5.5 years before abruptly ceasing the review. There were no differences in the patients' characteristics between patients who were still regularly followed and those abandoning the follow-up.

Late survival

Seventeen of the 268 hospital survivors (6%) died at a median of 8 months (5–25) after their repair. Four of these died of low output syndrome and two of sudden death. The others died of non-cardiac causes.

Survival at 5, 10 and 20 years was 95% (95% CI: 91–97%), 94% (95% CI: 91–97%) and 92% (95% CI: 86–95%), respectively. No predictors of late mortality could be identified.

Late reintervention

There were 66 reinterventions, including 48 balloon dilations and 18 reoperations, in 49 of the 268 survivors (18%). The first reintervention occurred at a median of 11 months (4–91) after repair.

The freedom from reintervention at 5, 10 and 20 years was 87% (95% CI: 83–90%), 84% (95% CI: 78–88%) and 72% (95% CI: 63–80%), respectively (Fig. 2).

Figure 2:

Freedom from late reintervention.

When comparing those patients with end-to-side repair through sternotomy with extended end-to-end repair through thoracotomy, 5-year freedom was 92% (95% CI: 79–94%) and 84% (95% CI: 74–90%), respectively, while 10-year freedom was 92% (95% CI: 79–94%) and 79% (95% CI: 66–87%), respectively (P = 0.220). By multivariate analysis, patch repair (P = 0.008) and not having a concomitant procedure (P = 0.018) were associated with the increased risk of reintervention.

Late reobstruction

A total of 87 of the 268 patients (33%) discharged from the hospital developed arch reobstruction. In addition to the 49 patients requiring reintervention, 38 patients presented signs of obstruction at latest echocardiogram. Freedom from reobstruction was 75% (95% CI: 69–80%) at 10 years and 45% (95% CI: 34–55%) at 20 years (Fig. 3).

Figure 3:

Freedom from reobstruction.

By the multivariate analysis, predictors of reobstruction were end-to-end anastomosis (P = 0.001), extended end-to-end anastomosis by thoracotomy (P < 0.001) and having a patch repair (P < 0.001) (Table 3). Ten-year freedom from reobstruction after end-to-side repair through sternotomy was 92% (95% CI: 79–97%), compared with 61% (95% CI: 48–75%) after extended end-to-end repair by thoracotomy (P < 0.001). Six out of the 10 patients (60%) who underwent a patch repair suffered reobstruction.

Table 3:

Risk factors for late reobstruction

Variable	Univariate P-value	Multivariate
		P-value	Hazard ratio (95% CI)
End-to-end anastomosis	0.015	0.001	3.47 (1.72–7.01)
Extended end-to-end anastomosis	0.003	<0.001	2.76 (1.67–4.57)
Subclavian flap repair	0.001
Patch repair	0.003	<0.001	4.71 (2.18–10.19)
Early reintervention	0.040
No associated cardiac procedure	0.030

Interestingly, 21 (43%) of those who underwent a reintervention still had a gradient exceeding 25 mmHg across their repair site afterwards, suggesting residual arch obstruction. Residual flow obstruction was slightly more common after balloon dilation (48%, 16 of 33) than after surgical repair (31%, 5 of 16) although this was not statistically significant (P = 0.3).

Late hypertension

Two-hundred and forty-nine patients had their casual blood pressure measured by their cardiologist at the last follow-up at a median of 12.3 years (8–17). Forty-five (18%) patients were hypertensive and another 35 (14%) were pre-hypertensive. The prevalence tended to increase with the age: 3–7 years 14%, 8–12 years 13%, 13–17 years 20% and over 18 years 27%, but advancing age was not statistically associated with hypertension.

There was a lower prevalence of hypertension in the patients who underwent an end-to-side repair through sternotomy than in patients who underwent an extended end-to-end repair through a thoracotomy (14 vs 20%, P = 0.4).

Seventeen of 45 (38%) hypertensive patients had arch obstruction on the latest echocardiogram (P = 0.018). Requiring an arch reintervention after hospital discharge did not correlate with the occurrence of late hypertension at last follow-up (17 vs 18%, P > 0.05).

Blood pressure measurements were available in 84 patients with reobstruction. Of these, 21 (25%) were hypertensive. Of the 47 patients post-reintervention and with available blood pressure measurements, 8 (17%) were hypertensive. Of the 58 patients with gradient exceeding 25 mmHg and with blood pressure recordings, 17 (29%) were hypertensive. The prevalence of hypertension was similar after balloon dilation (16%) and reoperation (19%) (P = 0.825).

Left ventricular outflow obstruction at the time of initial repair was associated with a higher prevalence of hypertension (38 vs 16%, P = 0.013). Left ventricular outflow tract obstruction at the time of the initial arch repair (P = 0.013) and arch obstruction at the last follow-up (P = 0.018) were the only independent predictors of hypertension at the last follow-up.

Preoperative arch dimensions and late outcomes

Preoperative proximal arch dimensions could be calculated retrospectively in 66 of the 89 patients for which the first echocardiographic examination was available. Patients who had a proximal aortic arch diameter z-score of less than −2 appeared more likely to require a late reintervention than those with a z-score greater than −2 (15 vs 0%, P = 0.1).

DISCUSSION

It is now more than 60 years since we began performing coarctation repair and there is still debate on the best procedure to achieve long-lasting successful results. Additionally, the exact incidence of hypertension late after repair is still unknown. Even in recent reports, the quoted incidence of hypertension after repair varies as widely as 17 and 48% [1–3, 5]. Residual aortic arch obstruction has been clearly identified as one of the predominant risk factors to become hypertensive after repair [4]. This fact has not deterred surgeons to continue to perform the vast majority of coarctation repairs via a thoracotomy, even when the aortic arch is smaller than normal, because there has been a general belief that small transverse aortic arches would grow to normal dimensions after repair [11–13]. We challenged this belief and found that the proximal transverse aortic would not always grow after repair, making us to suspect that these patients may be prone to develop hypertension [6]. We therefore decided to investigate the incidence of arch reintervention and hypertension in this patient population.

Hypoplasia of the aortic arch is a concept that is poorly defined because the size of aortic arch that will ultimately lead to late hypertension is still unknown. Ideally, arch hypoplasia should be defined following the subsequent risks of late adverse outcomes, but these data are not yet available. In most of previous publications, hypoplasia of the aortic arch has been defined on the basis of variation from normality extracted from studies of autopsied specimens [14]. Our old policy was to report transverse arch hypoplasia when the transverse arch in millimetres was less than the weight of the baby plus one in kilograms [9] and other centres adopted this method [15]. Some studies reported the size of the arch in terms of ratio of the transverse arch diameter to the descending aorta diameter [16]. We did not find our old definition reliable and have found the size of the descending aortic arch to be of great variability. Therefore, we now opt to report transverse arch size in terms of z-score. We wanted to investigate outcomes well into the second decade after surgery and accurate details of aortic arch sizes were not available retrospectively for these patients. We therefore selected our population on the rather subjective criteria that the aortic arch was quoted to be small.

Our seemingly high mortality of 9% can easily be understood in the view that this mortality almost exclusively occurred in patients requiring more extensive surgery for associated cardiac lesions. Our mortality of 1% in patients with no associated lesions compares favourably to other reports [15, 17–19].

Since the mid-1980s, Melbourne has favoured the technique of end-to-side anastomosis performed through a sternotomy for the repair of interrupted aortic arches and of coarctation of the aorta associated with hypoplastic arches [9]. Like others, we have found this policy to be very effective to protect patients against the risk of reintervention and reobstruction [9, 17, 20, 21]. It seems that we would have achieved better long-term outcomes in the present patients' population if this technique had been more widely applied. In the vast majority of cases (95%), a sternotomy was used only when coexisting cardiac lesions had to be repaired. We have recently demonstrated the success of a strategy of one-stage repair for interrupted aortic arch and the present study seems to confirm the benefits of one-stage repair in patients with multiple lesions and hypoplastic arch. Unfortunately, the remaining patients were repaired with other techniques, mostly through a thoracotomy, resulting in a quarter of these patients requiring reintervention and a half in obstruction. It is likely that those suffering from reobstruction are those who had the smallest aortic arches and that proximal hypoplasia of the arch was not satisfactorily relieved by repair. These results have influenced us to now perform the end-to-side technique through sternotomy in a much larger set of patients with the hypoplastic arches. We believe that, if the arch is small, the benefit of a complete relief of the arch obstruction outweighs the risk of the cardio-pulmonary bypass, the inconvenience of left laryngeal nerve palsy and the unfavourable cosmetic aspect of the sternotomy scar.

A third of our patients suffered from hypertension or pre-hypertension at the last follow-up and it is likely that this proportion would be higher if we undertook screening of this population with 24 h blood pressure monitoring [3]. This proportion seems unacceptably high when one considers that hypertension at this young age may prove fatal [1, 22]. It is interesting to note that only very few of those who had reintervention remained hypertensive at the last follow-up. While one cannot exclude neuro-humoural factors being responsible for the hypertension observed in some of these patients, it seems more likely that a number of these smaller arches remained small over the long term even though they did not produce an echocardiographic gradient that would qualify them as having obstruction.

It may seem surprising that the age at operation did not stand out as a predictive factor for any of the adverse outcomes studied, but it is likely related to the fact that the vast majority of our patients were operated as neonates. Favourable results after extended end-to-end repair of coarctation of the aorta have been reported and it is usually believed that this technique more adequately relieve arch hypoplasia [15, 23, 24]. It was our surprise to observe that subclavian flap repair which does not address the narrowing of the arch was not a risk factor for adverse outcome in this series and this may have been related to a selection bias. Because of the risk of the development of aneurism, this procedure has been abandoned in our centre.

Because of the high incidence of hypertension and arch reobstruction, these patients require regular follow-up into adulthood. We found it alarming that more than half of our patients over 15 years of age had no cardiology review in the 2 years preceding the study.

Not surprisingly, those patients with small left heart structures were at additional risk of death, reobstruction and hypertension. We found a similar correlation in patients with interrupted aortic arches [7], and it is likely that patients with smaller left ventricular structure also have smaller outflow tracts and smaller ascending aorta.

Limitations

Because this series ranges over 25 years, the results presented may not accurately reflect current practice. The patients were not randomly assigned to the various surgical procedures and therefore the design of the study may not have allowed us to compare adequately all techniques employed. For example, because the end-to-side technique was favoured, it is possible that patch repair was reserved to patients with complex features. We believe, however, that the comparison between interventions performed by thoracotomy and sternotomy remains valid.

Echocardiograms were only available in a third of patients, limiting us in our ability to predict the size of the aortic arch associated with the adverse outcome if operated through a thoracotomy.

It has now been demonstrated that 24 h blood pressure monitoring is the most sensitive method to detect hypertension in this population and it is likely that the incidence of hypertension would have been higher with this diagnostic modality.

Conclusion

After coarctation repair, half of the patients with hypoplasia of the transverse arch will develop residual arch obstruction and a third will become hypertensive. The technique of end-to-side repair performed through a sternotomy seems to alleviate these issues, and could be offered to a larger proportion of patients with hypoplasia of the aortic arch. Many of these patients cease being followed-up during adolescence at a time when ongoing care seems mandatory. Further studies utilizing 24 h blood pressure monitoring as well as more careful follow-up of these patients are required to detect the true burden of hypertension and reobstruction in this population.

Funding

This work was supported by the Victorian Government's Operational Infrastructure Support Program. Y. d'Udekem is a Career Development Fellow of The National Heart Foundation of Australia (CR 10M 5339). Ajay J. Iyengar is a co-funded Postgraduate Scholar of the NHMRC/National Heart Foundation of Australia (APP1038802), and holds a RACS Catherine Marie Enright Kelly Postgraduate Scholarship.