PART III - COARCTATION OF THE AORTA
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Updated on November 20, 2020
PART III

Coarctation of the aorta

Tomohito Kogure1,2, Benjamin G. Smith3, Shakeel A. Qureshi1
1Evelina London Children’s Hospital, Paediatric Cardiology, London, UK
2Tokyo Women's Medical University Hospital, Cardiology, Tokyo, Japan
3Royal Hospital For Children, Paediatric Cardiology, Glasgow, UK

Summary

First described by Morgagni in 1760, coarctation of the aorta refers to a congenital stenosis of the aorta most commonly seen in the periductal region [1]. There is local arterial medial thickening with superimposed neo-intimal tissue [2]. The natural history of the condition is dismal, with death ensuing on average in the fourth decade of life and three quarters of patients dying before their fiftieth birthday [3]. The most common modes of death are congestive cardiac failure, rupture of the aorta, endocarditis and intra-cranial haemorrhage [3, 4].

The first surgical repair of isolated coarctation was undertaken in 1944 [5]. With the subsequent evolution of surgical practice and techniques, the results of repair are now excellent [4, 6]. In parallel, the outcome of surgical repair of aortic arch hypoplasia has also improved dramatically over the last 50 years [6].

As in the case of many other surgical endeavours, percutaneous interventions for coarctation have been developed over the last two decades and offer an attractive alternative to surgery. Balloon angioplasty of coarctation was first described in 1982 [7] and stenting in 1993 [8]. Both techniques now play an important role in mainstream practice and, in the correct setting, are associated with excellent results [9]. Even complex arch anatomy, hypoplasia of the transverse arch and coarctation associated with aberrant origins of head and neck vessels can now be addressed percutaneously [10]. The use of breakable and biodegradable stents may become real soon [11, 12, 13] and the progressive reduction in the size of sheaths required for their deployment may allow the procedure to be undertaken in infants and young children patients, who required surgical procedures until recently. The recognition that coarctation constitutes only one part of a condition, including abnormalities of compliance of the aorta and the peripheral vasculature, may explain the frequent resistance of systemic hypertension to the relief of obstruction [14]. It is in this area that much work is required and is being conducted.

Coarctation and aortic arch morphology

Coarctation of the aorta accounts for approximately 7% of cases of congenital heart disease [15]. In classical form it occurs at the aortic isthmus, around the site at which the fetal arterial duct arises [6, 15]. Frequently there is post-stenotic dilation of the descending aorta immediately distal to the coarctation segment [2]. Diffuse hypoplasia of the aortic arch and isthmus is often associated with this [6]. Hypoplasia is widely accepted as being present when the diameter of the transverse arch is 60% or less than that of the aorta at the level of the diaphragm [9, 16]. In the case of severe coarctation, closure of the duct after birth will result in critical aortic obstruction, left ventricular dilatation and a rapid deterioration in the left ventricular contractility associated with metabolic acidosis. Untreated, death ensues quickly. However, in less severe forms of coarctation, the anomaly may become apparent during childhood when a murmur may be heard and the femoral pulses found to be of reduced volume [2]. In adult life, the most common presentation is with systemic hypertension [6]. In adolescent and adult patients, a haemodynamically significant coarctation is regarded as being present if there is a difference between the upper and lower limb systolic blood pressure of at least 20 mmHg [2, 9, 17, 18, 19], or less than 20 mmHg in the presence of systemic hypertension [16, 19].

The morphology of the aortic arch varies considerably, which usually follows a regular, semi-circular curve. However, there may be an acute angle between the proximal and distal segments known as a gothic arch, in reference to the similar angle seen in the architraves of gothic period windows and doors ( Figure 1). The arch assumes the apex of a triangle, with an increased height to width ratio. This is seen in 40%-45% of cases of coarctation. Conversely, in 10%-15% the arch may assume three sides of a square. This is referred to as crenal morphology [20]. Occasionally the normal, semi-circular arch is referred to as romanesque morphology [21]. It has become increasingly apparent that arch morphology is important in the long-term prognosis following the repair of coarctation, independent of the relief of obstruction [20]. Such morphologies are clearly of the utmost importance when considering stenting of coarctation and the hypoplastic arch. Of similar importance is the branching pattern of the head and neck vessels. A normal left-sided aortic arch (an arch which crosses the left main bronchus) results in the first vessel being the brachiocephalic (or innominate) artery, which divides soon after take-off into the right subclavian and common carotid arteries. The second vessel to arise is usually the left common carotid artery and the third the left subclavian. However, extensive variation in the branching pattern of head and neck vessels may be seen, most commonly an aberrant right subclavian artery arising from the aortic arch as the most distal vessel. In this situation, the coarctation usually occurs proximal to the aberrant artery [6]. Pseudocoarctation refers to a fold in the aorta which may give the appearance of coarctation on imaging modalities, but which may not represent a true stenosis of haemodynamic significance [16].

Coarctation of the aorta may occur in isolation but is commonly found in association with other anomalies. A bicuspid aortic valve is seen in 60% to 80% of patients [2, 18]. Other serious associated defects, such as the Shone complex (sub-aortic stenosis and supra-valve mitral ring) or hypoplastic left heart syndrome may co-exist. These associated anomalies support the haemodynamic hypothesis for coarctation pathogenesis; that its development is at least in part explained by decreased antegrade aortic flow in utero [2].

EVALUATION

Clinically, evidence for the presence of an aortic coarctation will usually take the form of systemic hypertension and may include a difference in upper to lower limb systolic blood pressure of at least 20 mmHg, reduced volume femoral pulses, brachio-femoral delay and an inter-scapular systolic murmur [2, 16]. There may be an associated ejection click arising from a bicuspid aortic valve. An electrocardiogram may demonstrate left ventricular hypertrophy and strain pattern [2]. Echocardiographic images may be challenging to acquire in adults. Aliasing on colour flow Doppler analysis can be absent in large patients due to acoustic drop-out, and the precise anatomy of the obstruction is rarely evident [22]. Spectral Doppler analysis is more useful and may demonstrate an elevated velocity across the distal aortic arch. It must be remembered that the modified Bernoulli equation used to estimate the gradient across the coarctation can be fraught with experimental error. This can be due to complex arch anatomy, flow dynamics and difficulty in aligning the Doppler beam with the blood flow. Conversely, extension of antegrade flow into diastole is a highly specific finding suggestive of coarctation [18] ( Figure 2).

Of particular importance is the assessment of systemic hypertension. Other than in the case of marked hypertension and the requirement for polypharmacy to control this, it is important to establish whether or not the patient is truly hypertensive. Blood pressure may be falsely elevated on a single reading in the consulting room in association with patient anxiety. Conversely, hypertension may not always be apparent on spot measurements of blood pressure [19]. This is of particular significance when imaging suggests a relatively mild degree of stenosis and a decision must be made as to whether catheterisation is justified. It is unwise to leave the decision whether or not to intervene until during the cardiac catheterisation itself. Blood pressure differences between the upper and lower limbs at rest correlate with invasive haemodynamic findings [18]. However, under general anaesthesia, the gradient on invasive measurement may be lower than when awake due to reduced sympathetic drive. A young patient with a blood pressure outside the 95th centile for age may be deemed normotensive if current adult guidelines are used. For this reason, centile charts should be used to assess hypertension in adolescents rather than applying general guideline values applicable to middle-aged patients. A 24-hour ambulatory assessment of blood pressure may be required to demonstrate hypertension and/or a lack of diurnal variation. Subtle elevations are not benign and may result in progressive vascular damage that may be irreversible. The interventionist must exercise particular caution when assessing adolescents with hypertension that appears too mild to treat. Importantly, the adverse effects of hypertension on vascular complications can be modified by actively lowering the blood pressure. In patients with a systolic blood pressure of 140-159 mmHg, a sustained reduction of just 12 mmHg over 10 years will prevent one death for every 11 patients treated [23]. Finally, hypertension may only be unmasked during exercise, and consideration should be given to undertaking a cardio-pulmonary exercise test in borderline cases.

Outside the consulting room setting, the imaging modality of choice for coarctation is Magnetic Resonance Imaging (MRI) [24]. Multi-planar spin echo (‘black blood’) techniques provide images of the aortic arch, in which precise measurements of the aorta can be obtained. Gadolinium-enhanced magnetic resonance angiography enables the construction of excellent 3D images, though it must be remembered that the rendering process is operator-dependent and may result in images that do not match those obtained by angiography ( Figure 3). Flow patterns can be generated, allowing an estimation of the pressure gradient across the coarctation. Computed Tomography (CT) can also provide detailed images of the arch and coarctation, but this is at the expense of significant radiation exposure. This is particularly important given that stenting is undertaken using fluoroscopy, and post-stenting follow-up may require the use of CT.

THE MANAGEMENT OF COARCTATION

The standard management of native coarctation in infants and young children is surgical repair, with first-line therapy in older children, adolescents and adults being percutaneous intervention.

SURGERY

The first surgical repair of coarctation was undertaken in 1944 by Crafoord and Nylin [5]. Since then, surgical techniques have progressed steadily, with the subsequent development of a number of repair methods. Surgical mortality in uncomplicated cases of native coarctation now stands at less than 2% [15, 25]. Initial procedures were associated with high rates of re-coarctation and this led to the use of patch aortoplasty in the 1950s. The technique gained popularity due to the limited aortic dissection required and lower aortic cross-clamp time compared with end-to-end anastomosis. This was in turn associated with a reduction in surgical mortality and morbidity, notably post-operative paraplegia. However, aortoplasty was plagued by a high incidence of aneurysm formation and delayed development of re-coarctation, particularly when using Dacron® (Invista Inc., Wichita, KS, USA) [6, 15]. Aneurysm formation was especially seen following a patch repair during early infancy. Surgical preference now is to minimise the use of prosthetic material [6].

The first of the two most commonly used contemporary techniques is the subclavian flap repair. First undertaken in 1966, the left subclavian artery is ligated and the stump tissue is used to patch the aorta at the coarctation site [26]. The main advantage of the technique is its use of autologous material, which has the potential subsequently to grow with the child, and the avoidance of a circumferential suture line which might lead to recoarctation post-operatively. However, the subclavian flap repair leaves a portion of native coarctation tissue in-situ. Like ductal tissue, this has the potential to contract during fibrosis, causing re-coarctation. Rarely, the technique also results in deficient growth of the left arm. The second technique in frequent use is the end-to-end anastomosis. Regarded as the superior technique by many surgeons, it provides complete relief of obstruction without the use of prosthetic material and completely removes all coarctation tissue. Furthermore, the technique can be modified in an extended end-to-end or end-to-side anastomosis to manage more extensive arch hypoplasia. The main disadvantages remain a longer cross clamp time and a circumferential suture line. Should there be significant fibrosis along this line post-operatively, there may a recurrence of coarctation [6].

In adults, the longer length of the coarctation segment and reduced elasticity of the aorta and reduced ability to mobilise the distal aorta may make end-to-end anastomosis difficult, necessitating either an interposition graft or extra-anatomical bypass in some cases. The larger aorta in adults necessitates a longer cross clamp time to place sutures, increasing the risk of paraplegia. Selective left heart bypass is now commonly utilised to decrease this risk. Other concerns associated with the surgical management of coarctation in adults are the potential for ruptured cerebral berry aneurysms and coronary ischaemia in the setting of accelerated coronary artery disease, which may be exacerbated by coarctation-induced systemic hypertension [6].

The immediate technical results of surgery are excellent, with complete relief of obstruction being seen in the vast majority of patients. However, in keeping with coarctation being only one part of a generalised vasculopathy, long-term follow-up demonstrates significant morbidity and mortality [4]. Life expectancy remains reduced and is significantly affected by the age at repair, early surgery being associated with improved survival [19]. The survival in patients alive at 30 days post-operatively is 95% at 10 years. However, freedom from the composite of death, re-intervention and cardiovascular complications (excluding hypertension) is only 60% three decades after surgery, whilst survival itself falls to 70% at 40 years. It must be remembered that the few studies examining long-term outcome are necessarily based on an historic patient population representing surgical techniques less developed than those of today [4]. Nevertheless, all patients must be followed up indefinitely.

In more than 70% of patients, late death is the result of a cardiovascular complication. The cause of death in one third of patients following successful coarctation repair is coronary artery atherosclerosis, often associated with systemic hypertension. Hypertension is frequently and indefinitely problematic following coarctation repair. Only 32% of patients are normotensive 30 years after repair. A full discussion of long-term hypertension can be found towards the end of this chapter. The rate of re-coarctation has decreased from as much as 44% in neonates to 11% in older children. The risk is lower in adults, being less than 10%. Approximately 10% of patients develop aneurysms at or near the site of coarctation repair. These may rupture, with disastrous results. The risk is highest following subclavian flap and graft repairs. End-to-end anastomosis carries the lowest risk of aneurysm formation at 3% [18]. The risk of endocarditis at the repair site is low, at around 1 per 1,000 patient-years [4, 18], but appears to increase with age or time after surgery. The co-existence of a bicuspid aortic valve is not a benign finding and should be considered a disease of the aortic root [4]. Serious complications such as aortic root dilatation develop in at least one third of these patients [18]. The valve may develop progressive calcification with stenosis and/or regurgitation. Aneurysms of the circle of Willis are found in 3% to 5% of patients with coarctation, including those who are normotensive [18].

FOCUS BOX 1Surgical repair of coarctation
  • Surgical repair of coarctation is indicated in infants and young children in whom results are excellent
  • Patch aortoplasty is associated with post-operative aneurysm formation
  • Re-coarctation can complicate both subclavian flap repair and end-to-end anastomosis
  • Hypertension remains a significant long-term problem

BALLOON ANGIOPLASTY

Balloon angioplasty increases the luminal cross-sectional area of the aorta by indiscriminately disrupting the arterial intima and media [6]. It has been shown to have excellent acute efficacy in the management of both native and recurrent coarctation in children [2, 27, 28]. Angioplasty is also a relatively safe and effective means of managing suitable, discrete coarctation anatomy in adults [2, 15, 29]. The technique compares favourably with surgical repair with respect to blood pressure control, the reduction of the coarctation gradient and complication rates in the short term [29]. However, there is an average rate of recurrence of coarctation across all ages of 15% to 25% [15, 27]. This rate is particularly high in the context of native infantile coarctation, being in the order of 40% to 83% [6, 18, 25, 27, 29]. Furthermore, following balloon angioplasty, there is a 10% to 15% risk of late aneurysm formation [18, 22, 23, 27]. This may relate to the fragility of ductal tissue. An aneurysm develops when there is an area of dilation of at least 150% of the aortic diameter at the diaphragm [17], or a discrete saccular dilation at the coarctation site of at least 110% of the diameter of the adjoining lumen that was not present prior to intervention [16, 22, 30]. The high rate of recurrence of coarctation and concerns regarding the potential for aneurysm formation and dissection have led to primary stenting superseding angioplasty in the majority of situations. The main indication for balloon angioplasty is now in the management of early re-coarctation following surgical repair in infants, in whom further surgery is best avoided and stenting holds significant drawbacks [2]. In this context, arterial sheath size is minimised in order to avoid damage to the femoral artery and consequent leg ischaemia. A number of low-profile balloons of various inflation pressures are available. Early re-coarctation due to scarring following repair in infancy may respond to a dilation at a low inflation pressure [15]. In this context a balloon such as the Tyshak II® (NuMED, Hopkinton, NY, USA) can be used. Higher pressure balloons such as the Advance® series (Cook, Bloomington, IN, USA) may be required, but may increase the risk of dissection and post-dilatation aneurysm formation.

Balloon angioplasty has been used as rescue palliation in neonates with critical obstruction. It is effective in reversing heart and multi-organ failure, therefore improving the clinical condition of the infant prior to surgery [25, 27, 28]. In order to avoid injury to the femoral artery, access can be gained via the umbilical artery in over 90% of cases. However, it is certainly not a definitive management strategy in this age group, proving either incomplete or permitting early re-coarctation in 50% to 73% of patients [28].

FOCUS BOX 2Balloon angioplasty for coarctation
  • Is indicated in re-coarctation in infants and young children
  • Provides excellent acute relief of obstruction in native and recurrent coarctation
  • Is associated with a high rate of re-coarctation, particularly in native lesions in neonates and infants
  • Is associated with aneurysm formation

STENTING

Stenting for coarctation was developed in the 1990s [15, 31] and is now the primary treatment of coarctation in the majority of older children, adolescents and adults. Its main advantages lie in being able to overcome the elastic recoil seen after balloon angioplasty [15] and, in the case of covered stents, the ability to exclude small dissections from the vascular compartment and reduce the rate of aneurysm formation [2]. Stenting results in a greater reduction in coarctation gradient and an improved coarctation diameter when compared with balloon angioplasty [15] and is superior in the management of associated diffuse hypoplasia of the aorta [17]. Stent use in infants and young children is currently challenging in most cases due to the lack of availability of stents that can be subsequently dilated to adult size and the prohibitively large sheath sizes required [11].

INDICATIONS FOR STENTING

The European Society of Cardiology and the American Heart Association (AHA) provides a class 1 recommendation of catheter-based stenting in adults with a significant aortic coarctation [32, 33], regardless of symptoms but with upper limb hypertension (>140/90 mmHg in adults), in the native aorta or in recurrent coarctation that was previously intervened upon. Aortic coarctation is defined as significant if there is a peak-to-peak resting gradient or mean Doppler-estimated gradient of greater than or equal to 20 mmHg between the upper and lower extremities. Additionally, a significant coarctation is an upper extremity to lower extremity peak-to-peak gradient or mean Doppler gradient of greater than or equal to 10 mmHg in the presence of decreased left ventricular systolic function, aortic regurgitation, or demonstration of collateral flow around the coarcted segment. The AHA adds that these physiological data should be accompanied by advanced imaging, including Computed Tomographic angiography or cardiac Magnetic Resonance Imaging [33]. The strongest indication for intervention includes a patient with systemic hypertension, a mean Doppler or peak-to-peak gradient of greater than or equal to 20 mmHg between the upper and lower extremities, and anatomically significant coarctation as confirmed by advanced imaging [33]. Milder obstructions may also benefit from intervention by decreasing the left ventricular diastolic pressure and preserving the left ventricular function in the long term, especially in the presence of hypertension at rest, abnormal blood pressure response during exercise, progressive left ventricular hypertrophy, elevated end-diastolic pressure and in cases of other complex heart defects, particularly those after Fontan operations [34].

The spectrum of symptoms and examination findings that inform the indications for the procedure vary among infants compared with children and adults. Older adults typically display manifestations of a 20 mmHg systolic gradient between the upper and lower extremities, systolic hypertension, and symptoms such as headaches. Uncommonly this group may have associated ventricular dysfunction and diastolic hypertension. Children and young adults may be asymptomatic but with elevated systolic blood pressure with less frequently associated headaches. In addition to the pathophysiologic gradients and confirmation of coarctation by advanced imaging, other factors need to be understood in the decision-making process of surgical or transcatheter management [35]. These parameters include age at presentation, if the coarctation segment is native or recurrent, and the complexity of the lesion. Transcatheter management is favoured as a temporary measure in neonates and infants too unstable for surgical management.

CONTRAINDICATIONS TO STENTING

There are few absolute contraindications to coarctation stenting. This is evident from the growing literature describing the procedure in the setting of hypoplastic transverse arch, unusual arch morphology and aberrant head and neck vessel branching patterns. Currently, the main contraindication is in the young infant and child. Given the concern for femoral arterial injury with large sheath placement, stent utilization is typically not advised in patients weighing less than 25 kg. In addition, placing a stent in patients less than 30 kg necessitates repeated stent dilatations as they grow. Exceptions may need to be made in cases of the extremely sick neonates with critical coarctation and circulatory collapse. In these, it is usually possible to relax the peri-aortic ductal tissue with prostaglandin. Metabolic acidosis may then improve, reducing the risk of subsequent cardio-pulmonary bypass and surgery. However, occasionally this approach may be ineffective, even with high prostaglandin doses. The infants may develop very poor left ventricular function with progressive metabolic acidosis and multi-organ dysfunction. The risk of cardiac arrest upon the induction of anaesthesia is high, and may not permit the establishment of cardiopulmonary bypass to facilitate surgical repair. In this case, the infant may be taken to the catheterisation laboratory for palliative stenting of the coarctation. Pre-mounted stents such as Palmaz Genesis® (Cordis, Bridgewater, NJ, USA) series of stents can be deployed through a 4 French sheath as a rescue procedure. Rather than providing definitive treatment of the condition, the aim is to allow reperfusion of the lower body and the correction of acidosis. This is followed at a later date by surgical removal of the stent and repair of the coarctation in a patient now much more able to tolerate a bypass procedure. Whilst the calibre of the femoral artery in infants prohibits the use of the larger French size sheaths required to deploy stents, particularly if covered, considerable success has been achieved in the stenting of coarctation in infants over one year old. The relief of obstruction and increase in aortic calibre are comparable to results seen in larger patients. However, serial stent dilation is required in parallel with somatic growth [36].

Pseudocoarctation, a folding in the aortic wall, may not be apparent until the patient is catheterised and a sizing balloon gently inflated (at less than 2 atmospheres) to demonstrate unfolding of the aorta [16]. A modest gradient may preclude the need to intervene.

PLANNING THE PROCEDURE

Having established the need for stenting, the procedure must be planned. This phase is vitally important and must be careful and fastidious [37]. Coarctation stenting is a technically challenging procedure, and great effort must therefore be made to reduce the possibility of unexpected findings and events during the procedure. A good quality MRI is essential in this process. Diameter measurements on black blood images should be made of the transverse arch, the aorta immediately proximal and distal to the coarctation, and the aorta at diaphragmatic level. Equipment is ordered on the basis of the intended final stent diameter being approximately the average between the aortic dimensions at the transverse arch and at the diaphragm. Whilst experience suggests measurements on black blood images tend to provide an underestimate of calibre in comparison with angiographic images at catheterisation, the degree of error does not ordinarily result in a significant departure from the equipment initially selected. The length of the coarctation segment is measured, starting (in the case of it being in the usual position) from the left subclavian artery. The measurements are used to plan which stent and balloon assembly are likely to be required, and therefore which size of sheath is necessary. It must be remembered that most stents shorten when expanded [2]. Information specific to each stent is available from the manufacturer. Careful measuring on MRI ensures the appropriate equipment, including stents of a size larger and smaller than that required, and spares are obtained well before the procedure is undertaken. In the case of patients in whom the femoral pulses are reduced or absent and with a history of previous arterial access, it cannot be assumed the abnormality of pulses is wholly due to the coarctation. A vascular ultrasound assessment of the femoral arteries should be obtained prior to catheterisation to be sure the vessels are suitable for use.

IN THE CATHETERISATION LABORATORY

Access to the femoral artery and vein are gained. The puncture should be under direct ultrasound guidance to ensure a central point of entry, given the size of sheath that will be required. Fluoroscopy of the femoral head prior to puncture provides landmarks that help ensure the common femoral artery is entered, but if ultrasound guidance is used, then fluoroscopy is not essential for access. In the case of severe coarctation or complete interruption, access to the right radial artery is also gained. In this scenario the coarctation is best crossed antegradely with a fine guidewire which is then snared from below the coarctation and exteriorised from the femoral artery. After gaining arterial access, the femoral artery must be imaged angiographically to assess its size and suitability for insertion of a large sheath and for preparation of a vascular closure device. The entry point of the vessel is also assessed and must be below the inguinal ligament. Spasm can be addressed with the local instillation of isosorbide mononitrate.

General anaesthesia reduces sympathetic drive and may result in a falsely low gradient across a coarctation. It must also be remembered that the gradient may be reduced in the presence of a well-developed collateral circulation [2]. In the case of a gradient of less than 20 mmHg, most operators advocate stenting if there is at least a 50% reduction in aortic calibre at the site of coarctation [19]. A positive chronotrope such as isoprenaline, or inotrope such as dopamine, can be given in order to unmask a gradient [38]. However, the decision to stent should have occurred prior to catheterisation. The patient is systemically heparinised and the Activated Clotting Time maintained at over 200 seconds. The coarctation must be crossed carefully with a soft-tip wire to minimise the risk of lifting a dissection flap. In the case of severe narrowing, initial dilation with a low profile balloon (such as a coronary balloon) may be required prior to advancement of a long sheath across the coarctation, although this is not essential.

The usual angulations of x-ray tubes for visualising the aortic arch are straight lateral, left anterior oblique (sometimes with caudal angulation) and shallow right anterior oblique (to avoid super-position of the ascending and descending aorta) [9]. A stiff guidewire with a J-tip such as the Amplatzer® (Abbott Structural Heart, Plymouth, MN, USA) series is placed across the coarctation. Some operators advocate positioning the distal end of the wire in the left or right subclavian artery to ensure the balloon remains straight upon inflation, in order to reduce balloon curvature and the potential for rupture [2]. However, this practice may be associated with distal stent migration during balloon inflation. This complication is reduced by positioning the guidewire in the aortic root. A temporary pacing lead is placed in the right ventricle and should be tested for capture and to demonstrate a reduction in ascending aortic systolic blood pressure to 50 mmHg or below during rapid ventricular pacing. This method provides the operator with a greater degree of control over stroke volume than the use of adenosine-induced bradycardia or asystole, the onset and resolution of which cannot be finely controlled. However, in the presence of a tight aortic coarctation, pacing may not be needed. The use of intra-vascular ultrasound may potentially add a safety margin to the procedure. Vessel wall abnormalities such as medial and intimal disruption dating from previous interventions can be identified. This may aid in the selection of a stent required to cover the abnormal segment, which is frequently longer than the angiographic stenosis [15].

A large variety of balloons is available for coarctation stenting. The most commonly used are the Z-MED™ (NuMED), CORDIS® (Cordis), Cristal (Balt, Montmorency, France) and Balloon-in-balloon (BIB®) series (NuMED; Figure 4), the availability of other balloons will influence the operators’ choice. The BIB® balloons provide a greater degree of control over stent position afforded by a step-wise inflation and also significantly reduce the incidence of balloon rupture and stent migration [15]. All sizes run over a 0.035 inch guidewire. The inner balloon has a diameter half that of the outer and is one centimetre shorter. BIB® balloons range in outer diameter from 12 to 24 mm and in length from 2.5 to 5.5 cm in multiple combinations. The Cristal balloon is a high pressure, semi-compliant balloon designed to provide a predictable diameter at set pressure above or below the nominal pressure. This information is found on a compliance chart packaged with the balloon. The balloon is available in a diameter of 8 to 40 mm and a length of 2.0 to 4.0 cm. Again, all sizes run over a 0.035 inch guidewire.

Similarly, multiple stents are available. In patients who are not yet fully grown, a stent that can later be dilated to 25 mm or more should ideally be selected [15]. Early in the evolution of coarctation stenting, the Palmaz® (Cordis) 8 and 10 series were used. However, they and other older stents tended to have sharp points at the apex of each cell. This resulted in balloon ruptures and dissections [16]. Stents now have more rounded ends and the balloon technology has improved, minimising ruptures. Latterly, the LD series (Medtronic Inc., Minneapolis, MN, US) and Cheatham-Platinum (CP™; NuMED) series (covered and uncovered) have become increasingly popular. The Intrastent™ LD family are all composed of a stainless steel tube cut into an open lattice design. All have rounded cell edges to reduce the risk of balloon rupture and do not shorten until expanded beyond a diameter of 12 mm. The LD Max™ is available in lengths of 16, 26 and 36 mm and provides high levels of strength. The LD Mega™ is designed to lie somewhere between the two, providing both moderate strength and flexibility. It is available in the same lengths as the LD Max™. The AndraStent XL and XXL (AndraMed GmbH, Reutlingen, Germany) consist of a cobalt-chromium hybrid (semi-open) design and are characterised by offering high radial force with minimal recoil, ideal for dealing with resistant lesions. They are available in lengths of 13 (XL only) and 17 to 57 mm, and can be expanded from 8 (XL) to 32 (XXL) mm. Their strength ensures stent fracture is exceedingly unlikely [39]. All stents are uncovered.

Cheatham-Platinum (CP) stents are composed of a platinum / iridium wire arranged in a “zig-zag” pattern, laser welded at each joint and over-brazed with gold ( Figure 8.png" data-toggle="modal" data-target="#popup-media" class="media-link" data-media_id="1516" data-folder="pcr-textbook" data-chapterid="130"> Figure 7.png" data-toggle="modal" data-target="#popup-media" class="media-link" data-media_id="1515" data-folder="pcr-textbook" data-chapterid="130"> Figure 6.png" data-toggle="modal" data-target="#popup-media" class="media-link" data-media_id="1514" data-folder="pcr-textbook" data-chapterid="130"> Figure 5). The stents are available in lengths (unexpanded) of 16, 22, 28, 34, 39 and 45 mm and can be dilated from 8 to 24 mm. The degree of shortening upon expansion increases with final stent diameter and can be predicted from charts packaged with the stents. All CP stents are available either in bare metal form or covered with a sleeve of expandable polytetrafluoroethylene (ePTFE; Gore-tex, WL Gore and Associates, Flagstaff, AZ, USA). Other than when stenting across aortic arch vessels, covered stents are favoured due to the increased safety they provide in covering dissection points and preventing aneurysm formation [15, 40]. This is especially important when there is a particular risk of vessel injury, such as in severe coarctation, patients with advanced age, pre-existing aneurysm or aortic wall irregularities, or a connective tissue disorder [15]. Recently introduced is the NuDEL™ (NuMED) which is all-in-one stent delivery system designed for the efficient and effective treatment of CoA. It includes the covered CP stent, mounted on a BIB balloon catheter, which is then covered by a sheath (stent, balloon, sheath: all-in-one system). Pre-loaded system saves time and allows for quick actions in emergency situations [41].

BeGraft® Aortic stent (Bentley InnoMed, Hechingen, Germany) offers a covered stent alternative to the CP stent. This cobalt-chromium based stent is pre-mounted balloon-expandable stent-graft covered with micro-porous ePTFE tubing. This stent allows large postdilation diameter up to 30 mm. With availability of lengths of 19–59 mm and lower stent profile, they can be used in native and recurrent coarctation of the aorta in adults and in pediatric patients. The BeGraft® Aortic stent has received CE-mark approval in November 2016 for use in native and recurrent coarctation of the aorta in adolescent or adult patients and promising early outcomes were reported [42]. It has been proposed that the use of covered stents reduces the risk of aneurysms, dissection, and rupture [43, 44]. However, a randomized trial comparing the CP bare stent with the CP covered stent for severe native coarctation in adults demonstrated no difference in acute or follow-up aortic wall injury between the bare-metal and covered stents [45]. Nevertheless, covered stents offer the advantage of excluding any stretch-induced wall trauma from the endoluminal aspect of the aorta, particularly in the catastrophic event of aortic rupture as revealed by Coarctation of the Aorta Stent Trial (COAST) II study [46] which is a multi-center, single arm trial using the covered CP stent in treating or preventing aortic wall injury in patients with coarctation of the aorta.

A further available option is a self-expanding nitinol stent. Self-expandable stents have been used, because of their flexibility, conformability to the aortic anatomy and easy deployment. Furthermore, low constant radial force of these stents may result in a gradual widening of the stenotic lesion as well as leaving less tissue injury [47, 48].

OptiMed Sinus-XL stent (OptiMed Medizinische Instrumente GmbH, Ettlingen, Germany) was recently reported to produce satisfactory results with acceptable safety and efficacy and mid- to long-term outcome [49]. This stent is a self-expanding nitinol (shape-memory metal) stent, which is laser-cut without welding, with closed-cell design for maximal radial force. It is designed with sufficient flexibility to allow easy placement. The stent has 100-cm-long delivery system, which is designed to track over 0.035 inch guidewires. This stent system needs a 10F sheath for delivery and is available is sizes ranging from 16 to 34 mm in diameter and from 30 to 100 mm in length.

Pre-stenting angioplasty, whilst commonly performed in the past to assess the distensibility of the aorta, is no longer advocated [15, 22]. It is associated with an increased risk of intimal tears, aortic wall dissection and rupture, and the development of post-procedural aneurysm [22, 50]. For isolated coarctation in the usual location, a stent is usually dilated to no more than the diameter of the transverse arch and aorta at the level of the diaphragm, and frequently to a diameter somewhere between the two [9, 15].

The stent is deployed under low stroke volume conditions aided by rapid ventricular pacing. Following balloon deflation, it is important to advance the sheath over the balloon within the stent, rather than withdraw the balloon from the stent into the sheath in order to avoid dislodging the stent in the event of the balloon having become caught on the stent struts. Post-stent angiography can then be undertaken via the long sheath across the coarctation, or ideally from the radial approach, if available. In the absence of radial access, advancing a small calibre diagnostic end-hole catheter and subsequent withdrawal of the sheath to below the stent enables simultaneous pressures to be measured and a post-stent gradient to be obtained. However, repeated manipulation of catheters and wires across the coarctation site must be avoided [9, 17, 27]. Flaring of the ends of the stent remains controversial. Whilst few would argue against modelling the proximal end of the stent to ensure good apposition to the aortic walls, many do not flare the distal end. The degree of obstruction relief is independent of distal stent flaring and the cosmetic angiographic result [9]. When there is significant post-stenotic dilatation (as is commonly seen), apposition of the distal end of the stent will not be possible anyway. Most operators will not aim to abolish completely the waist of a stent at the coarctation site as its presence is indicative of stable anchoring. Over-enthusiastic dilation of a stent to over 3.5 times the initial calibre of the aorta is associated with aortic wall injury [22]. It is better practice to accept a residual gradient and return for a subsequent dilation several months later [9, 15]. Though an immediate residual gradient of over 10 mmHg is associated with a higher rate of need for re-intervention and a follow-up gradient over 20 mmHg, a residual gradient of less than 20 mmHg is considered a haemodynamic success by most operators [15, 17, 22].

Arterial haemostasis is crucial after the use of the large bore sheath, which is often up to 14 French, required especially for covered stent implantation. It is good practice to keep a wire in the abdominal aorta whilst withdrawing the large sheath into the iliac artery and perform an angiogram. This should demonstrate satisfactory integrity of the vessel before the complete withdrawal of the sheath. Vascular closure is typically accomplished by partially deploying one or more suture devices, such as the Perclose ProGlide™ (Abbott Vascular, Santa Clara, CA, USA), after initial access prior to upsizing the arteriotomy beyond 8 F, which allows the arteriotomy to subsequently be enlarged to the large-bore 14–16 F sheath, and closed after the procedure by tightening the knot(s) [51]. Great care must be taken to ensure good management of the femoral artery post-procedure, both to maintain satisfactory perfusion of the leg and to preserve the artery for potential future catheterisation. Loss of a pulse may require the use of systemic anti-coagulation or thrombolysis. If doubt exists over the integrity of the vessel, ultrasonic assessment must be undertaken urgently. Discharge of a patient with anything other than complete confidence in vessel integrity is fraught with danger. The two main complications that must be aggressively managed are ischaemia with potential damage to the leg, and retro-peritoneal bleeding, which may not be clinically obvious until the patient deteriorates. Such deterioration may be rapid and fatal. In the case of a reduced or absent femoral pulse, the interventionist must clearly be mindful of these two possibilities when considering anti-coagulation or thrombolysis.

Post-stenting, most patients can be managed at ward level. Frequent assessment of pulses and basic observations is mandatory. Rebound hypertension should be aggressively managed if the blood pressure is higher than 160/110 mmHg. The aim in an adult is to achieve a blood pressure no higher than 150/90 mmHg [16]. It is usual practice to maintain a patient on the same anti-hypertensive medication prescribed prior to stenting, at least until the first follow-up appointment. An anti-platelet medication such as aspirin or clopidogrel is given for six months to reduce the incidence (albeit low) of thrombus formation on the stent prior to endothelialisation.

DIFFICULT CASES

Whilst initially undertaken only for simple, discrete coarctation, stenting is now used increasingly in the setting of the anatomically complex coarctation [31, 37]. For near-atresia, the coarctation is best crossed antegradely from a radial approach, using a very soft-tip guidewire such as a coronary wire. The wire is snared in the distal descending aorta beyond the coarctation and externalised at the femoral arterial site, providing retrograde access across the coarctation for a low-profile balloon. Once a circuit is established, the coronary wire can be changed to 0.035 inch exchange length guidewire. This will allow the larger sheath to be passed through the coarctation site. In case of resistance, occasionally serial increases in balloon size may be required before the stenosis will permit passage of the large sheath ( Figure 8.png" data-toggle="modal" data-target="#popup-media" class="media-link" data-media_id="1516" data-folder="pcr-textbook" data-chapterid="130"> Figure 7.png" data-toggle="modal" data-target="#popup-media" class="media-link" data-media_id="1515" data-folder="pcr-textbook" data-chapterid="130"> Figure 6). Complete interruption of the aorta may be approached with either the high tip load coronary guidewire such as the ASAHI Astato XS 40 wire (Asahi Intecc, Nagoya, Japan) carefully advanced antegradely to a waiting snare, or the stiff-end of the wire or by radio-frequency perforation or transseptal puncture needle [44, 52]. Clearly all the approaches entail an increased risk of dissection, and so the use of a covered stent is mandatory. In aortic re-coarctation following surgical repair, post-operative aneurysm formation may be managed at the same time as obstruction by the use of telescopically deployed covered stents [37]. Covered stents are also preferred in the management of previously fractured stents, tortuous anatomy and advanced age (in which case the risk of aneurysm formation is higher) [40].

The deployment of stents across the origin of head and neck vessels, whilst initially thought highly inadvisable, is now sometimes undertaken, at least with respect to the subclavian arteries [10, 16]. In this case, bare metal stents are favoured as they do not compromise distal perfusion in an otherwise normal vasculature. Some operators establish radial access prior to stenting and, following stent deployment, pass a wire through a cell of the stent lying across the vessel origin. The cell is then balloon dilated. When using a covered stent, the Gore-tex may be perforated, allowing cell dilation [53, 54].

Whilst transverse arch hypoplasia with associated coarctation is ordinarily repaired surgically in infancy with good results, management of such hypoplasia using bare metal stents in older patients is well described. The peak-to-peak systolic gradient can be reduced to less than 10 mmHg and the calibre of the hypoplastic segment increased to at least 90% of the adjacent aorta in 90% of patients [10, 55]. Angioplasty alone in this setting should be avoided, as a residual gradient of over 20mmHg is seen in almost 60% of cases [17].

STENTING IN NEONATES AND SMALL CHILDREN

Neonates with severe CoA in a critical unstable haemodynamic state may be at an increased risk with surgical treatment. The risk of cardiac arrest upon the induction of anaesthesia is high, and may not permit the establishment of cardiopulmonary bypass to facilitate surgical repair. In this case, life-saving emergency interventional treatment using mostly coronary stents can be performed [56, 57].

According to several case reports and published small series, stabilisation of the clinical condition can be achieved for a few weeks allowing for later elective surgical treatment [36, 58]. Ideally a single stent should be used for the longer term in neonates, which should also allow for growth of the child. Such a stent does not exist for wider clinical use and the different technologies, such as biodegradable scaffolds, growth stents or dilatable stents are now the focus of research [11, 12, 13].

Biodegradable scaffold technology is developing slowly and a limited number of case reports have been published, so this is still work in progress [59, 60, 61]. The first pediatric use of a Magmaris® vascular scaffold (Biotronik AG, Bülach, Switzerland) in a low birth weight infant with aortic coarctation and distal arch hypoplasia was reported recently [12]. In addition to that pediatric poly-L-lactic-acid-based bioresorbable scaffold (Elixir Medical Corporation, Milpitas, CA, USA) was introduced with promising preclinical data [60].

The Osypka BabyStent (Osypka, Rheinfelden, Germany) is a low-profiled, balloon-expandable cobalt-chrome stent, which is breakable to permit unrestricted growth, is being evaluated to treat aortic CoA in infants. Preliminary experience with off-label implantation of the stent in four high-risk babies and infants presenting with restenosis after earlier surgical repair of aortic coarctation has been reported [11, 62].

In children, low profile open-cell stents, such as Cook Formula stents (Cook medical, Bloomington, IN, USA) or Valeo Stents (Edwards Lifesciences, CA, USA), can be redilated to nearly adult size without significant loss in radial strength [63, 64]. These may also be used in small children as a bridge to anticipated surgery [57, 64, 65]. However, these stents may be of inadequate calibre for an adult aorta and there are concerns that the large gaps between the stent struts that exist at full expansion may allow a prohibitive degree of neo-intimal proliferation [66].

To minimise arterial damage, a new type of sheath, Glidesheath Slender (Terumo, Tokyo, Japan), can be used with 1 F reduced external diameter compared with other sheaths [67]. In this, the outer diameter of the 5 F sheath is the same as a conventional 4 F sheath. This may be worth considering for use in small babies [68].

PROCEDURE SUCCESS

Stent placement in aortic coarctation and recoarctation was successful in 99% of the 105 children and adults who underwent stent implantation in the COAST study [69]. Two systematic review papers reported that the procedural success rate was 98%, the coarctation diameters increased to three times (from about 5mm to about 15mm) the initial calibre of the coarctation, and the pressure gradient deceased from 40 ~ 45 mmHg to less than 5 mmHg [70, 71].

ACUTE COMPLICATIONS

Although endovascular stenting has reduced the invasiveness of the treatment of coarctation of the aorta, it is associated with some complications. In a systematic review of forty-five publications (with a total of 1,612 patients), death was uncommon (0.4%), despite the occurrence of aortic dissection (0.9%) and rupture (0.4%). [70]. Noted risk factors for acute aortic wall complications include pre-dilatation balloon angioplasty, abdominal aortic location of the coarctation, and patients over forty years of age [16]. The formation of aneurysms has been reported after stent implantation with an incidence of 1.5 %. The aetiologies of these aneurysms may be attributed to overstretching of the vessel wall with balloon dilation and diminished quantity of elastin fibres with an increased collagen component. The contribution of stretching of the vessel wall leading to wall trauma and the above-described sequelae may be minimized with the use of covered stents [46].

Stent migration may occur in 2.4 - 2.7% of cases [70, 71]. This occurs mainly when deploying a stent on a balloon that is 2 mm or more greater than the diameter of the aorta proximal to the coarctation site, but may also result from deploying a stent on an under-sized balloon in the setting of pseudocoarctation, and from balloon rupture.

Additional complications may be related to the femoral access, including limb ischemia and hematoma and were reported in 2.2 % of the cases [71]. These complications can be reduced nowadays by the utilization of vascular closure devices [51].

DELAYED COMPLICATIONS

The incidence of aortic aneurysm formation following stenting is reported in 5.7 % of cases, most commonly at the site of the narrowest segment of the coarctation [22]. The majority of aneurysms are small and can be managed conservatively. Larger aneurysms may require exclusion with a covered stent or stent graft [9] ( Figure 8.png" data-toggle="modal" data-target="#popup-media" class="media-link" data-media_id="1516" data-folder="pcr-textbook" data-chapterid="130"> Figure 7). There is no evidence for aneurysm formation occurring more frequently in recurrent versus native coarctation or in cases of a high balloon: coarctation ratio, and there is no association with the type of stent used. However, there is an association between exceeding a balloon: coarctation ratio of 3.5:1 and evidence of aortic wall injury on follow-up imaging studies. In the case of bare metal stents, neo-intimal proliferation resulting in in-stent stenosis is seen more commonly in patients stented at a younger age. Over-dilating the stent at implantation may also be associated with an increased risk of subsequent neo-intimal proliferation [22]. Fracture of stents may occur within two years following stenting. However, this generally does not result in a loss of stent integrity or recurrence of a gradient [69]. The rate of re-interventions was around 10% which was including stent re-dilatation in order to account for the patients' somatic growth and to address aneurysms [70].

FOLLOW-UP

Patients are ideally assessed three months after coarctation stenting with adjunct imaging [16]. It may be possible to wean anti-hypertensive medication at this time.

A thorough physical examination includes four-limb blood pressure under resting conditions. Twenty-four hour ambulatory blood pressure recordings and exercise testing should be considered in the case of an apparent and rapid resolution in previously resistant hypertension. An electrocardiogram is mandatory [19].

Whilst echocardiography provides a useful office-level assessment of left ventricular thickness and function, arch patency and an estimate of the arch gradient, it does not provide adequate assessment of the aortic wall and therefore cannot be used to exclude complications [22]. Similarly, a chest x-ray is insufficiently sensitive to detect aortic wall complications. The two modalities of imaging most commonly used are CT and MRI. CT has ubiquitous availability in developed countries and its attractions are obvious. It is fast, high quality images are obtained, the stent is well-visualised and complications such as stent fracture, in-stent stenosis, aneurysm formation and dissection are readily appreciated [24]. However, the assessment of flow and a residual gradient are not possible. Of chief concern is the need for significant radiation exposure, particularly as patients require serial imaging and may require further catheterisation.

MRI has much to offer. Modern stents are non-ferrous and are not a contraindication. Whilst stent artefact prevents the direct evaluation of in-stent stenosis and stent fracture, dissection and aneurysms can be visualised ( Figure 8). Isotopic 3D volume balanced steady-state free precession sequences enable highly detailed evaluation of stent position and detection of aortic wall complications. MRI can also provide an assessment of left ventricular mass, volume and function, and aortic valve function [24]. All are important in the overall assessment following coarctation stenting. CP™ stents do not cause excessive artefact. However, the LD Max™ and Mega™ stents cause such a degree of artefact that CT is preferable.

Following demonstration of a satisfactory result on either CT or MRI, patients should be re-imaged approximately every three years, though there is no evidence for the optimum time interval. Anti-hypertensive medication can be weaned as tolerated.

FOCUS BOX 3Stenting of coarctation
  • Stenting of coarctation is indicated in both native and re-coarctation in older children, adolescents and adults
  • Biodegradable scaffolds, growth stents or dilatable stents are now the focus of research in neonates and small children
  • Careful planning prior to catheterisation is essential
  • The main complications are stent migration and aneurysm formation
  • Follow-up must include imaging such as CT or MRI

Comparing surgery, balloon angioplasty and stenting

All 3 treatment modalities have shown low acute mortality rate and significant improvement in systolic blood pressure [72]. However, a recent meta-analysis showed that balloon dilation is less likely to achieve treatment success as measured by the proportion of patients achieving a blood pressure gradient of ≤ 20 mmHg when compared with stenting. Furthermore, more patients undergoing balloon dilatation experienced severe complications during admission (6.4%) compared with stenting (2.6%) [73]. Stenting may thus be considered advantageous when compared with balloon angioplasty in older patients but with reservations in neonates or small children.

Transcatheter stent therapy is a safe, effective, and less invasive alternative to surgery in suitable anatomy. However, unlike surgical therapy, which has robust long-term outcome data, there are limited long-term clinical and haemodynamic outcome data after transcatheter stent therapy. An observational study by the CCISC (Congenital Cardiovascular Interventional Study Consortium) showed that both stent implantation and surgery achieved excellent hemodynamic results in the short term [74]. Stent patients had shorter hospitalization than surgical patients (2.4 vs. 6.4 days) and fewer complications than surgical (2.3%, 8.1%) though planned re-intervention was more likely in the group of stented patients [74]. This finding was relatively consistent with the previously reported results [75].

The incidence of re-intervention after surgical repair is approximately 10% [15]. The concerns pertaining to paraplegia and aneurysm formation following patch arterioplasty are well documented. The rate of re-interventions after stenting was 8.7% occurring during the two-year follow-up period and included stent re-dilatation in order to keep pace with the patients' somatic growth and dealing with aneurysms [69].

Despite favourable results of stenting in the short term, there is a concern that inserting a stiff metal stent into an already stiff arterial system that was exposed to chronic hypertension may negatively influence vascular properties and add to the ventricular after-load, which could influence long-term outcomes. The most recent observational study showed that the transcatheter group of patients had less regression of LV hypertrophy and less improvement in LV systolic and diastolic function indices during the mid-term follow-up, although both transcatheter and surgical therapy resulted in a similar acute hemodynamic improvement [76]. Therefore, as transcatheter stent therapy becomes more widely used in the coarctation of aorta patients, longer term follow-up will be important to determine the clinical impact of some of the observed differences between the 2 approaches.

Long-term hypertension

With such high rates of success in the relief of aortic arch obstruction following stenting and surgery, the effectiveness of both in treating hypertension remains disappointing [19, 23]. Hypertension is a significant long-term concern, as blood pressure is a key determinant of late morbidity and mortality after repaired coarctation [23]. It is present in 20% to 40% of patients 10 to 20 years after repair and is even more prevalent in those followed for longer periods. The most important predictor of problematic hypertension long after repair is the age at operation. The lowest rate is seen in those repaired under one year of age [18].

The blood pressure should be measured in all four limbs on an annual basis [18]. The rigour of measurement is an important factor in the post-procedural assessment. Whilst a spot reading may be normal in the office, the majority of patients continue to display a sub-normal circadian variation on 24-hour blood pressure assessment (non-dipping) [19]. Hypertension on ambulatory blood pressure monitoring is a superior predictor of cardiovascular events compared with spot checks [18]; four times as many patients with residual hypertension will be identified by 24-hour ambulatory blood pressure monitoring compared with spot checks [77]. An additional and important investigation that must be considered in apparently normotensive patients following surgery or stenting is the exercise-stress test. 20% to 35% of normotensive patients post-coarctectomy show a non-invasive hypertensive reaction on exercise [18, 78, 79]. Correspondingly, 30% to 35% of normotensive patients with an estimated aortic gradient on Doppler echocardiography of less than 20 mmHg develop an increased gradient of over 40 mmHg during exercise, a finding confirmed by isoprenaline stress during invasive pressure monitoring under sedation [38]. An exercise-induced aortic arch gradient is seen more commonly in a small transverse arch, and is three times more common in gothic arches than those of the crenal or normal variety [18, 38]. However, 50% of patients with an exercise-induced gradient paradoxically have a widely and uniformly patent arch [78]. The clinical significance of these findings remains unclear, and there is debate as to whether such patients require pharmacological management [18, 78].

Clearly, long-term residual hypertension following either surgical repair or percutaneous management of coarctation is not simply related to the adequacy of obstruction relief [78]. After successful repair, increased left ventricular mass and abnormal systolic and diastolic left ventricular function persist, even with a normal resting blood pressure [18]. Certainly, persistent up-regulation of the renin-angiotensin system resulting from decreased renal blood flow in the presence of coarctation is important [2, 18]. Arterial compliance declines with age due to increased fragmentation and decreased density of elastin, and increased collagen content and cross-linking [21]. Furthermore, it is now well established that patients with coarctation have abnormal peripheral vascular function rather than purely an isolated, mechanical obstruction [14, 15, 78]. In patients with coarctation, vascular stiffness in the proximal aortic segment is increased and distensibility is decreased, due to excess collagen and deficient smooth muscle [1]. Gothic arch morphology is associated with a higher degree of arterial stiffness and an increased intima-media thickness of the pre-coarctation arteries, which is associated with hypertension and increased left ventricular mass [20, 21]. Patients with coarctation also have impaired endothelium-dependent and independent dilation, which further contributes to an increased systemic vascular resistance [14, 21]. The dysfunction of the vascular bed can be demonstrated years after relief of obstruction [1]. In the case of stenting, at six months post-procedure, baseline aortic elasticity remains reduced (and is negatively correlated with the initial aortic pressure gradient) and aortic stiffness elevated [80] Given hypertension is the prime determinant of coarctation-induced morbidity, the long-term efficacy of stenting remains to be seen.

FOCUS BOX 4Hypertension following surgical repair or percutaneous management of coarctation
  • Is related to a pervasive vasculopathy characterised by arterial stiffness, independent of any residual aortic obstruction
  • Is frequently seen many years after repair or intervention
  • Is an important determinant of long-term morbidity and mortality
  • May require 24-hour ambulatory measurement and exercise-stress assessment for detection
  • Necessitates an assessment of the need for further intervention, which frequently reduces the requirement for anti-hypertensive medication

Takayasu Arteritis

Takayasu arteritis is a rare, chronic inflammatory disease of large arteries. There is a preponderance amongst females of Asian descent in the second decade of life. The cause is unknown. An acute phase of constitutional symptoms is followed by a chronic phase months to years later, during which arterial complications occur. Ultimately, all three arterial wall layers fibrose. The disease causes stenosis, occlusion and aneurysm formation in a patchy distribution, resulting in characteristic ‘skip-lesions’ [81]. Due to the non-specific nature of symptoms at presentation and the initial absence of clinical signs, most patients remain undiagnosed until the chronic or ‘pulseless’ stage of the disease. The two stages are not always distinct and infrequently coexist at different sites [82]. Claudication and hypertension are common [81, 83]. Mortality is up to 30% at five years [84]. In 50% of such cases this is due to congestive heart failure resulting from hypertension or aortic regurgitation. Only 28% of patients achieve sustained remission [83].

Angiography is essential for planning open bypass surgery and endovascular management [82]. A classification system is used to describe vessel involvement, the most common pattern being disease of the entire aorta and its primary branches above and below the diaphragm [81]. The first signs are localised narrowing or irregularity of the vessel lumen. Later there is stenosis or occlusion, or dilation and aneurysm formation (both saccular and fusiform) [85]. Angiography provides information on luminal anatomy rather than the vessel wall itself and requires the use of radiation and nephrotoxic contrast medium. MRI is therefore an important adjunct [81]. Subtle mural thickening can be demonstrated in the pre-stenotic inflammatory stage. However, as yet there is no conclusive evidence that MRI findings accurately correlate with disease activity or progression. This may be resolved by the advent of gadolinium-DTPA-enhanced three-dimensional MRI [82] and positron emission tomography, in which deoxyglucose (a glucose analogue) is labelled with Fluorine-18 (a positron-emitting radionuclide). Uptake is increased at sites of inflammation in large vessels (> 4 mm) [85].

Therapy during the acute phase of Takayasu arteritis is usually medical and consists of corticosteroids and sometimes cytotoxic immunosuppression. Later, surgical bypass grafting is required for long segment disease. Grafts must be anastomosed to healthy tissue [81]. Provided the disease is in the chronic phase, surgery is highly successful, with a mortality rate of less than 5%. However, mortality can nevertheless be high. Complications may include anastomotic site aneurysms (in up to 10% of cases) and graft occlusion, potentially resulting from flare-ups of “inactive” lesions [81, 82, 83]. Surgery during the acute phase results in a higher incidence of anastomotic stricture and pseudoaneurysm formation [81, 82]. Progressive inflammation and uncertainty regarding disease stage can limit surgical management [86].

Endovascular management is minimally invasive, cost-effective and safe [82, 86], though long-term durability remains unestablished [81, 82]. It avoids the morbidity associated with exposure of large vessels in the abdomen and thorax [81]. Whilst many lesions are short and amenable to angioplasty or stenting [81, 87], there are no clear guidelines for selecting endovascular therapy over surgery [82]. The repeatability of balloon dilation makes it first-line management in paediatrics [88]. In adults there should be ischaemic symptoms (such as claudication and renovascular hypertension), focal rather than long segment stenosis of over 70% to 75% and a clinically chronic disease phase [82, 86]. In comparison with coarctation of the aorta, it is generally recommended that the gradient across the stenotic area should be at least 50 mmHg [86, 89]. Stenosis can be very rigid and require high pressure balloons (over 15 atmospheres) to improve vessel calibre [87, 88, 89]. Severe lesions require graded dilation. A balloon diameter of 60% to 100% of the adjacent normal vessel diameter, but no more than three times the stenotic segment, reliably results in a significant reduction in gradient and increase in mean luminal diameter [81, 87, 89]. There is frequently a further improvement in vessel calibre and gradient over the next few months and an improvement or cure of hypertension [87, 89]. However, following balloon dilation alone, stenosis ultimately tends to recur. Stenting is often required to maintain a satisfactory result, particularly if the lesion is ostial or long, or if there is chronic occlusion. When dilating the para-renal aorta it is advisable to maintain a guidewire in each renal artery, given the potential for dissection with extension into the artery origin [88]. A few case reports showed promising results of using drug-coated balloon for peripheral vessel regions of Takayasu arteritis in short-term, though longer term efficacy is unknown [90, 91, 92].

Conclusive evidence for the use of an anti-platelet such as aspirin or ticlopidine before and after balloon dilation or stenting is lacking [87, 88]. However, most operators prescribe aspirin indefinitely following intervention [86]. It has been suggested that prednisolone should be given for six months following intervention to prevent a flare-up in disease [86, 89]. Endovascular therapy during acute inflammation should only be undertaken, if there is life-threatening hypertensive encephalopathy and congestive heart failure [82]. Should this be necessary, a concurrent course of steroid therapy should be considered [86].

Small intimal tears following angioplasty are frequent [88]. However, in comparison with coarctation, the incidence of aneurysm formation is very low, presumably due to tough fibrosis of the entire vessel wall [89]. Rare cases of dissection or aneurysm formation can be managed with stent grafting [93]. However, the area may also require stenting, given the insufficient radial strength of stent grafts in this setting. Complications such as stroke, acute thrombosis, severe dissection, myocardial infarction, emergency surgery and death are particularly rare [86].

FOCUS BOX 5Takayasu Arteritis
  • Takayasu arteritis is a rare, idiopathic, chronic inflammatory cause of transmural fibrosis of the aorta and its major branches
  • Angiography is required for planning surgery or intervention, though MRI better predicts disease stage
  • Surgical bypass grafting is required for long-segment disease. It can be associated with a high mortality and complication rate
  • Endovascular intervention is most effective for short lesions. For stenosis, high pressure dilation and stenting is often necessary
  • Serious complications following endovascular intervention are rare

Personal perspective - TOMOHITO KOGURE

Transcatheter stent therapy has been established as a less invasive alternative therapy to surgery in older children and adults. This practice is based on robust data demonstrating a comparable acute hemodynamic improvement after transcatheter stent therapy. However, there are still limited long-term clinical and hemodynamic outcome data after transcatheter stent therapy. It is postulated that the rigidity of the stented segment of the aorta may affect the compliance and flow characteristics of the thoracic aorta. In addition to that, the vasculopathy associated with coarctation is already well described that there is a reduction in aortic distensibility and elasticity, which does not resolve following relief of coarctation by any means. Hypertension therefore does not simply resolve after successful treatment of obstruction. Despite adequate intervention and drug therapy, patients with coarctation of aorta have a reduced life expectancy and increased risk of cardiovascular complications later in life. MRI may provide means of assessing aortic stiffness and vascular resistance prior to and after stenting potentially non-invasively. This could in turn help predict the need or otherwise for ongoing medical management of hypertension following the relief of obstruction. Re-coarctation should be proactively addressed. Cardiovascular complications may occur decades after initial treatment, warranting lifelong follow-up.

As demand for less invasive solutions increases to coarctation of aorta in infant and small children, the need for a robust, appropriate diameter low-profile bioresorbable and biodegradable scaffolds to provide a long-term solution to vessel rehabilitation is vital. Over the past few years, much progress has been made toward the development of such scaffolds. Ultimately, the performance of the scaffold in real life aortic coarctation in small infants is yet to be evaluated. Future clinical trials of such devices are needed with the hope of finding a suitable option for a population that remains underserved in this regard.

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