Coarctation of the aorta: natural history and outcome after surgical treatment

Coarctation of the aorta (Figure 1) accounts for approximately 5% of all congenital heart disease and is found at necropsy in up to 1:1550 patients.1 It is approximately three times more common in males.2 The traditional classification into infantile (preductal) and adult (postductal) types is now regarded as too simplistic, since many patients with preductal lesions do not present until adulthood.3 A spectrum of lesions is now recognized, and it is only those with the most severe obstruction (e.g. aortic arch atresia or interruption) or associated cardiac defects who invariably present in infancy. Most other cases are now identified at routine medical examination. Otherwise, age at presentation is related to the severity rather than the site of obstruction, as a result of cardiac failure or occasionally cerebrovascular accident (CVA), aortic dissection, or endocarditis. Coarctation of the aorta was not regularly diagnosed clinically until after 1933.4 Details of the natural history of aortic coarctation are therefore incomplete, being largely derived from hospital post-mortem records and selected case series prior to 1945, at which time operative repair was introduced. The first and largest post-mortem series was published by Abbott5 in 1928, who collated findings from all 200 previously documented cases over the age of 2 years, dating from the first report of aortic coarctation by Paris6 in 1791. Reifenstein, Levine and Goss7 subsequently reported 104 further cases from the literature dating from 1928 to 1947. The median age of death for all 304 cases was 31 years, and 76% of deaths were attributed to complications of the aortic coarctation.8 Cardiac failure accounted for 26% of deaths, at a mean age of 37 years. Aortic rupture (21%), bacterial endarteritis (18%), and intracranial haemorrhage (12%), occurred at a mean age of 25–29 years. Ten of the 31 patients dying from cerebral haemorrhage had ruptured cerebral aneurysms. Case selection in all post-mortem series was biased towards younger patients dying from complications directly associated with aortic coarctation, and older patients dying from either incidental causes or congestive heart failure would have been under-represented. Reasonable correlation exists between post-mortem data, and that derived from ante-mortem case series. Campbell8 reviewed and collated data from three of the four pre-surgical case series published between 1933 and 1956.2,4,9 In a combined cohort of 181 patients followed for a total of 716 patient-years, 22 deaths were observed, corresponding to a mortality rate of 1.6% per annum for the first two decades, and rising steadily to 6.7% for the sixth and subsequent decades. In the largest of these series,2 heart failure was the commonest cause of death, followed by bacterial endarteritis and intracranial haemorrhage. Campbell acknowledged the case selection bias inherent in this analysis, and recognized that as patients were by necessity symptomatic, they must also have had relatively severe coarctation. Successful surgical correction of coarctation of the aorta by resection with end-to-end anastomosis (EEA), was first described by Crafoord and Nylin in 1945.10 Subsequent advances in surgical techniques,11–13 including the introduction of subclavian flap aortoplasty (SFA),12 have allowed correction of the more complex anatomical variants. Percutaneous balloon angioplasty was introduced in 1982,14 and during the past decade, expandable endovascular stents15 have been increasingly used. Current perioperative mortality rates are determined largely by age and presence of concomitant congenital heart disease, rather than by choice of operative technique,16 and in recent series are approximately 2.6% for older children and adults.17,18 Only one author19 attempted to objectively classify surgical outcome into `good', 57% patients (femoral pulses normal, leg > arm blood pressure) and `satisfactory', 30% patients (minor improvement of femoral pulses, leg blood pressure <20 mmHg below arm). Approximately 80% of patients are asymptomatic for a median of 20 years following surgery.18–21 However, reports consistently show that patients are at an increased risk of developing cardiovascular disease despite successful anatomical correction, and that this risk is related to the duration of follow-up and the presence of hypertension. Complications related to the operative repair and to associated cardiac defects, notably bicuspid aortic valve disease, add significantly to mortality and morbidity (Table 1). Thus surgery and other interventional treatments modify rather than correct the natural history of coarctation. Since most patients have surgery before the age of 20 years, many of the complications observed occur in young adults. The first long-term follow-up study reported a 12% death rate in a cohort of 194 patients after a mean duration of 8.8 years.22 The mean age of death was 35.1 years, and mortality was especially high for those undergoing surgery after the age of 25 years. Most deaths were due to congestive heart failure, aortic rupture, myocardial infarction, or subarachnoid haemorrhage. Subsequent studies19,20,23 have confirmed these findings. One report suggested a better prognosis for patients undergoing operative repair by EEA, compared with other methods.20 However, pooling of data is difficult because of differences with respect to duration of follow-up (8–40 years), study population (children or mixed adults and children), operative technique, and events reported; some authors report only on mortality, whilst others concentrate on morbidity. Between 10%24 and 64%21 of patients were lost to follow-up, and the cause of death was unknown in almost 20% in one series.20 Actuarial survival figures demonstrate a marked increase in death rates for patients aged over 40 years when followed for 10 years or more, in comparison with younger patients.19 Recurrent hypertension is common despite successful repair of aortic coarctation, and is the major factor in the post-operative occurrence of cerebrovascular disease, aortic rupture, and heart failure, as well as accelerating the progression of coronary artery disease (CAD). Although most patients become normotensive following surgery, hypertension often recurs during long-term follow up. The reported prevalence of late hypertension depends on the diagnostic criteria used and on the duration of follow up, ranging from 30%18 to 75%.19 Cohen et al.18 (median follow up of 20 years) reported a prevalence of 8% in patients with systolic pressure >150 mmHg and diastolic pressure >90 mmHg, and 25% when isolated systolic hypertension was also included. The prevalence depended on the age at the time of repair; being 7% for those operated on at <1 year, and 33% for those operated on after the age of 14 years. Clarkson et al.19 found that the incidence of late hypertension was higher in patients with transient post-operative hypertension, and increased with post-operative follow-up. Presbitero et al.20 found that only 32% remained normotensive after 30 years. Koller et al.23 reported on a cohort of 362 patients, and demonstrated that when patients were operated on between the ages of 2 and 9 years, the prevalence of hypertension at 9 years follow-up was similar to that for a control population. This study also suggested that late hypertension occurring in patients operated on during infancy was usually associated with clinical evidence of recoarctation. Severe aortic regurgitation also accounts for some cases of isolated systolic hypertension.22 In general terms, the prevalence of hypertension is related to the age at operation and to the duration of follow-up. The cause of late hypertension is unknown, but several theories have been proposed, including decreased aortic compliance,25 abnormal baroreceptor function,26 and neuroendocrine activation.27 Subtle abnormalities can be demonstrated in a large number of patients post-operatively, despite normal resting blood pressure. Systolic blood pressure assessed by ambulatory monitoring is elevated in comparison with control subjects, and diurnal variation is reduced.28 Exercise-induced systolic hypertension is common,29 and has been noted in association with an exercise-induced gradient between upper and lower extremities. This may reflect either mild residual coarctation or differential arterial compliance. The relationship of these observations to late hypertension and long-term prognosis is unclear. Abbott included in her report a section on `Anomalies of the arteries taking origin from the aortic arch', but did not mention CAD.5 The reasons for this omission are unclear. Although many of the cases had been described in the nineteenth century, CAD was by then well recognized by pathologists, and the clinical features of coronary artery disease had been described by Herrick30 in 1912. CAD is not mentioned in either of Campbell's papers,2,8 but Reifenstein et al.7 reported it as the cause of 3/104 deaths in cases between 1928 and 1947. These figures contrast with the high incidence of deaths attributed to CAD in most post-operative series. Lawrie et al.31 attributed two-thirds of late deaths to acute myocardial infarction. In Cohen's series,18 the figure was 37%, but it may also have accounted for some of the 13% of sudden deaths and 9% of deaths caused by heart failure. Clarkson et al.19 reported similar death rates but an incidence of only 5% for angina in survivors. Stewart et al.21 described `evidence of ischaemic heart disease' in 23% of survivors, but this was based on only 42 of their original 149 cases. The evidence for CAD comprised coronary artery bypass grafting in three cases, and unspecified electrocardiographic (ECG) changes in the remainder. Cohen's data18 indicate that deaths due to CAD are related to the duration of preoperative hypertension and its recurrence or persistence post-operatively. Reports describing the occurrence of symptomatic CAD are suprisingly sparse, but the incidence is likely to be high and to rise with increasing time from surgery, as Vlodaver and Neufeld,32 the first to specifically study coronary artery histology, found marked intimal changes even in children, with conspicuous atherosclerotic changes in young men. One report20 found that cerebrovascular accidents (CVA) accounted for 11.5% of post-operative deaths; similar to that in the preoperative era, but the other major reviews found a much lower incidence, ranging from 0–7%.17,18 The occurrence of CVA may be related to the age of operation. In one report, all were older than 10 years at the time of surgery,24 and in another, older than 25 years.18 This is probably a reflection of the duration of hypertension in the cohorts studied. Several studies do not quote morbidity, although one that does,19 reported that four survivors (3%) had a CVA. Thromboembolic strokes probably result from premature carotid artery disease associated with pre-operative and post-operative hypertension, whilst haemorrhagic events may be the result of post-operative hypertension and pre-existing Berry aneurysms. Despite accurate anatomical reconstruction, local aortic complications including recoarctation, aneurysm formation, and rupture may occur during long-term follow-up, and all patients continue to be at risk of infective endarteritis. Identification of these complications may be difficult, and their incidence was probably underestimated in earlier series. Definitive diagnosis of structural aortic complications has traditionally relied upon contrast aortography (Figure 2), but echocardiography, computed tomography (CT), and magnetic resonance imaging (MRI) now provide often superior alternatives. Most studies have used clinical criteria to define recurrence of coarctation on the basis of a blood pressure difference of >20 mmHg between upper and lower limbs. Using these clinical criteria, recoarctation is predominantly associated with repair during infancy, and is uncommon in adult patients. In a 10-year follow-up study by Koller et al.,23 recoarctation occurred in 10.8% of infants undergoing repair at less than 2 years of age, compared with 3.1% of older children, and no adults. These results have been confirmed in other studies,16 although Presbitero et al.20 suggested higher rates in older patients. A study by Brouwer et al.33 suggested that infant weight was a more important predictor of recoarctation than age alone. Recoarctation appears to be more common in patients undergoing repair by SFA rather than EEA.19,20,34 Presbitero20 reported a prevalence of 8% for EEA compared with 35% for other procedures, and Clarkson et al.19 reported recoarctation rates of 17.5% for patients who were unsuitable for repair by EEA. Recoarctation is also more common in patients undergoing balloon angioplasty as an initial interventional procedure.35,36 In a small randomized trial,36 recoarctation occurred in 25% of children following angioplasty, compared with 6% following surgery. The time course for recurrent coarctation is uncertain, and in the many cases which are identified during the first year post-operatively, residual coarctation rather than recoarctation may be the explanation.24,33 Recoarctation is associated with both recurrent hypertension, and an increased mortality rate.20 Two-dimensional echocardiography sometimes allows direct visualization of the recoarctation site, although views are often obscured in adults,37 and trans-oesophageal imaging is no better in many cases. Spectral and colour doppler demonstrate high-velocity flow in the descending aorta in most instances, with characteristic prolongation of flow throughout diastole. However, doppler estimation of gradients do not always correlate well with measured gradients,38 and the rate of diastolic velocity decay as assessed by the `diastolic velocity half time', may be a more reliable indicator of severity.39 MRI offers several advantages over echocardiography, and is now considered the imaging modality of choice for the thoracic aorta.40 Imaging may be orientated in any plane, and allows both direct visualization of the recoarctation site, and accurate measurement of flow in the descending aorta using cine-MRI with velocity mapping (Figure 3).41 Peak velocity in the descending aorta as a measure of gradient, correlates well with cardiac catheterization.42 Although spiral CT with three-dimensional reconstruction provides impressive images of the aortic arch, it appears to be inferior to MRI for determination of both the nature and severity of recoarctation.40 Surgical repair of recoarctation is safe and effective, but balloon angioplasty is an acceptable alternative, and is the treatment of choice in many centres.13 In one study,43 72% of patients in whom dilatation was successful did not require further intervention during a 12-year follow-up. Aneurysm formation is a serious complication, which may occur either at the site of repair, or within the proximal aorta, and is associated with a significant risk of aortic rupture. Repair-site aneurysms are particularly common in patients who have previously undergone patch aortoplasty, occurring in up to 20% of cases.44 Knyshov et al.45 reported 48 cases (5.4%) of aneurysm formation in a series of 891 patients followed for up to 20 years post-operatively, of whom 90% had undergone synthetic patch aortoplasty. Eighteen of these 48 patients (37.5%) died during follow-up, as a result of either rupture or endarteritis. Balloon angioplasty is also associated with an increased risk of aneurysm formation. Rao et al.46 reported that 5% of children and infants who had angioplasty developed aneurysms at a mean follow-up of 14 months. Diagnosis of aneurysm formation is difficult, and has traditionally relied upon screening chest radiography followed by aortography. Magnetic resonance imaging is a non-invasive alternative to aortography, and can be used both for diagnosis, and for prediction of patients at risk of aneurysm formation.47 Patients found to have a repair site to diaphragmatic aortic diameter ratio of >1.5 are at high risk of progressive aneurysmal dilatation,48 and it has been suggested that 12–24 monthly MRI should be performed in high-risk patients47 Aortic rupture may also occur within the proximal ascending aorta, particularly in association with either a congenital bicuspid valve or XO Turner's syndrome.49 It may also infrequently occur distal to the site of coarctation as a result of cystic medial necrosis.50 Endarteritis, which was responsible for almost 20% of deaths in the pre-surgical era5 is uncommon in operated patients.20,24 Vegetations usually occur distal to the site of coarctation. The high-velocity blood jet at this site initiates endothelial trauma which encourages microbial adhesion, (as it does on the pulmonary artery opposite the jet from a patent ductus arteriosus). This is prevented by repair of the coarctation, which removes the high-velocity jet. Improved awareness of prophylactic antibiotic treatment prior to dental procedures or instrumentation has also helped. Endocarditis associated with bicuspid aortic valve disease may actually be more common than endarteritis occurring at the site of coarctation.49 A bicuspid aortic valve is found in 20%21 to 85%20,22,24 of patients. Significant stenosis and/or regurgitation develops in up to two thirds of cases,24 of whom at least 10% will require aortic valve replacement,21 since the natural history of bicuspid valve is of progressive deterioration after the fourth decade. It is associated with a risk of aortic aneurysm and dissection independent of aortic coarctation which may occur, as with the latter, even after surgery. Bicuspid aortic valve is responsible for many of the cases of cardiac failure, which accounts for up to 20% of late deaths.24 The impaired long-term prognosis and high morbidity of patients following surgical repair indicate the need for long-term follow-up. Screening ECG and chest radiography provide useful, but non-specific prognostic and diagnostic information. Following surgery, the ECG is normal in 25–48% of cases.20,21 Abnormalities include both right and left bundle branch block, and changes attributable to myocardial ischaemia. Left ventricular hypertrophy is found in up to 27%;24 the authors of this latter study reported that 87% of these patients had aortic valve disease, hypertension, recoarctation, mitral regurgitation or ventriculo-septal defect. The chest radiograph shows cardiomegaly in approximately 20% of cases,21,24 most of whom have hypertension or aortic valve disease. Regular screening and aggressive treatment for hypertension, and investigation for possible recoarctation in high-risk groups is essential. The blood pressure gradient between upper and lower limbs should be recorded at each visit, using a large cuff with auscultation over the popliteal artery. A blood pressure gradient of >20 mmHg should prompt further investigation for recoarctation, ideally by MRI with velocity mapping. Evidence of severe recoarctation is a relative indication for either balloon angioplasty or reoperation, particularly if hypertension is present. Patients with a previous patch aortoplasty should be screened at 12–24-monthly intervals by MRI for repair site aneurysms, which should be treated by reoperation. Clinical evidence of aortic valve disease warrants regular echocardiographic review (both for deteriorating valve function and for aortic dilatation), careful blood pressure control, and assessment for valve replacement along conventional lines. Screening and modification of cardiovascular risk factors is also essential, and a good case can be made for early pharmacological treatment of moderate hypercholesterolaemia. All patients should be advised regarding antibiotic prophylaxis for dental and other procedures. Risk factors for complications following repair of coarctation of the aorta Risk factors for complications following repair of coarctation of the aorta Chest radiograph demonstrating severe rib notching, prominence of the left subclavian artery, and cardiomegaly in an adult with juxtaductal aortic coarctation. Contrast aortogram demonstrating postductal coarctation. Selected frames from 0.5 tesla T2-weighted cine-MRI sequence. The left panel demonstrates a discrete shelf within the descending aorta at the level of the ductus. The right panel shows only mild turbulence (black) in the proximal aorta at from a pressure