Present and future status percutaneous interventions for adult congenital heart disease

Abbreviations

ASD: atrial septal defects

CHD: congenital heart disease

FA: femoral artery

ICE: intracardiac echocardiography

IE: infective endocarditis

IVC: inferior vena cava

LA: left atrium

LV: left ventricle

PA: pulmonary artery

PDA: patient ductus arteriosus

PFO: patent foramen ovale

PPVI: percutaneous pulmonary valve implantation

PV: pulmonary valve

PVE: pulmonary vein

RA: right atrium

RFV: right femoral vein

RVOT: right ventricular outflow tract

SV-ASD: sinus venosus Atrial Septal Defect

SVT: superior vena cava

TAVI: transcatheter aortic valve implantation

TV: tricuspid valve

VSD: ventricular septal defect

Take-home messages:

1. Percutaneous treatment has become a standard of care for many congenital conditions.
2. Nitinol memory metal has facilitated large devices being delivered through catheters.
3. Treatment of aortic coarctation in adults is predominantly percutaneous.
4. Percutaneous valve development for pulmonary valves was ahead of TAVI development and combines balloon-expandable and self-expanding technologies to allow most patients to be treated percutaneously.
5. TAVI and transcatheter edge-to-edge repair can be used to treat congenital heart patients too.

PDA occlusion

A patent ductus arteriosus (PDA) occurs when the arterial duct fails to close in early life, usually presenting in childhood with a murmur, failure to thrive or heart failure.  However, if there is little haemodynamic impact, it can present later in life with breathlessness, left ventricular dilatation, infective endocarditis (IE), heart failure, and rarely, pulmonary vascular disease [1].

In the absence of IE, percutaneous PDA closure is the treatment of choice with low risk and has a high success rate [2]. This differs from childhood treatment, as for many years the duct has had flow from the aorta to the pulmonary artery (PA). The duct usually tapers from the aorta with a narrow point in the roof of the left PA, such that it is often necessary to cross the duct from the aorta. Angiography should be performed prior to crossing the duct.  A Judkins left 4 catheter (JL4) from the femoral artery (FA) crosses and enters the PA easily.  Crossing the tricuspid valve (TV) with a balloon-tipped catheter, snaring the wire in the PA and exteriorising it without damage to the TV allows for the formation of an arteriovenous wire loop. A delivery sheath is advanced from the right femoral vein (RFV) and across the duct to deliver a nitinol wire device such as an Amplatzer Duct Occluder (Abbott), with the distal component in the aorta and the proximal in the PA. Coils are rarely used in adults, as there is space in the vessels for the nitinol wire plugs, which have a low chance of embolisation and low residual leak rates [3]. Symptomatic benefit and remodelling of the left ventricle (LV) is usually observed.

Atrial septal defects

The first devices for closure of the atrial septum were used in the 1990s, but with the licensing of the Amplatzer family of devices in the late 1990s, percutaneous atrial septal defects (ASD) and patent foramen ovale (PFO) closure rapidly took over the majority of secundum ASD closure and allowed PFO closure.[4]

Patent foramen ovale

PFO closure is primarily performed to prevent recurrent strokes in those who have already suffered a paradoxical embolus, which is supported by high quality randomised controlled trial (RCT) evidence [5]. Other indications include prevention of: embolic myocardial infarction, decompression illness for divers, migraines, positional oxygen desaturation (platypnea–orthodexia syndrome) or exertional desaturation [6].

The diagnosis is made using bubble contrast transthoracic echocardiography, and whilst helpful, transoesophageal echo (TOE) is not required to confirm the diagnosis.

PFO and ASD closure require periprocedural TOE or intracardiac echocardiography (ICE).  General anaesthesia is helpful for TOE. Ultrasound-guided puncture of the RFV is the usual access with a second puncture if ICE is used. 

Non-self-centring nitinol wire mesh devices and fabric covered frame devices are available and our local success rate at device implantation in a PFO is >99.5 % for over 1,500 procedures. Amplatzer devices and GORE CARDIOFORM Septal Occluders (GSO; W.L. Gore & Associates) featured highly in RCTs [7]. PFO closure should be extremely low risk with high success rates in experienced centres.  The most frequent complication is atrial arrhythmia, including atrial fibrillation (AF), but a meta-analysis demonstrated that the increased risk appears to only last around 45 days [8]. Residual shunts can occur and with Amplatzer devices are associated with presence of an atrial septal aneurysm (ASA) [9]. In our experience the GSO has a lower residual leak rate when an ASA is present.

Secundum ASD

Whilst the Amplatzer Septal Occluder (Abbott) was not the first device used to close secundum ASDs, it made the technique accessible and   first-line treatment. Other nitinol mesh devices include Figulla (Occlutech) and the differently designed GORE CARDIOFORM ASD Occluder (GCA) device, which retains a self-centring compressible waist with a larger disc on each side but has a nitinol wire frame encapsulated in Goretex (W.L. Gore & Associates) [10]. 

With 25 years of experience and different device designs, experienced centres can treat most ASDs presenting in adults percutaneously. The limiting factors are the lack of a rim to the superior vena cava (SVC) or PA, an absent rim inferiorly to the inferior vena cava (IVC), or a left atrium (LA) too small to accept the size of device required.  An absent aortic rim is common but not a specific contraindication. 

Initially, oversizing of devices was commonplace and may have contributed to the serious complication of device erosion, occurring in 1 in 1,000 patients treated with Amplatzer Septal Occluders [11]. Correct sizing is important; too small a device may embolise and too large a device may erode or fracture.  Complication rates are extremely low in experienced centres, and mortality is rare. Surgery is low risk, but recovery time and the long-term results of Amplatzer device-closure mean that surgery is only used when percutaneous treatment would not be possible safely.  

Complications and follow-up

Antiplatelet therapy is needed for both PFO and ASD devices for a period after implantation.  Our practice is to give clopidogrel 75 mg daily for 3 months and aspirin 75 mg daily for a minimum of 6 months.  For embolic indications, long-term aspirin is often recommended. 

Atrial fibrillation is the most common complication of PFO [8] and ASD closure, but as found in an internal audit of ASD patients, it can be persistent, whereas in PFO patients, if not present preprocedure, it will almost always resolve [8].  Patients with AF prior to an ASD procedure should be considered for a PV isolation prior to ASD closure, which, in our audit, reduced the likelihood of AF.

In older patients undergoing ASD closure the LA pressure can be high, especially if hypertensive.  Closing the septum can increase LA pressure leading to pulmonary oedema.  Consequently, for patients over 45 years and anyone with hypertension, we pretreat with angiotensin-converting enzyme (ACE) inhibitors/angiotensin receptor blockers and/or vasodilators and check LA pressure at the time of the procedure. If LA pressure is high, we test occlude the ASD and remeasure the pressure with a second catheter in the LA.  If the LA pressure rises dramatically, additional medical treatment may be needed.  Fenestrated occluders (which have a hole of a specific diameter within the device waist), may be needed for high LA pressure or if there is significant pulmonary vascular disease.

Superior sinus venosus - ASD percutaneous treatment

Superior sinus venosus (SV)-ASD is a complex defect of the superior aspect of the atrial septum associated with anomalous drainage of some of the right superior pulmonary venous drainage [12]. Percutaneous treatment is relatively new and requires detailed CT evaluation.  A large, long covered stent is placed, anchored in the SVC and protruding into the top of the right atrium (RA). This closes the connection between the atriums and excludes the pulmonary vein (PVE) from the RA, so its flow is directed behind the stent and into the LA.  A transseptal puncture is needed to enter the PVE behind the stent to measure pressure gradients and undertake angiography, and in some cases, to allow balloon protection of the pulmonary valve (PV) when the covered stent is expanded, to prevent PV stenosis. Currently, balloon-expandable 10- or 12-zig covered Cheatham-platinum (CP) stents are widely used, but specific stents, including self-expanding designs are being developed. This procedure is challenging and performed in a limited number of specialist centres but offers an alternative to surgery, particularly for higher risk patients.  This may treat a significant proportion of patients in the future but is unlikely to replace surgery altogether.

Ventricular septal defect

Those who reach adulthood with a congenital ventricular septal defect (VSD) rarely need intervention, but if there is volume load of the LV, aortic regurgitation due to cusp prolapse or infective endocarditis, VSD occlusion may be appropriate.  In the past, catheter intervention has been hampered by the proximity of the AV node leading to heart block, but newer designs of occluders are being used, mainly in the Far East, where VSD is more common.

Coarctation of the aorta

Balloon dilatation or surgery is the standard of care for neonates and small children with coarctation of the aorta [13]. However, for adults, angioplasty alone is less effective and can lead to aneurysm formation. Stenting of coarctations became common in the 2000s and subsequently balloon-expandable covered stents became available to reduce the risk of uncontrolled local dissection or aortic rupture [14]. Indications are usually poorly controlled hypertension, heart failure prior to aortic valve intervention and enlarging aneurysm or pseudoaneurysm [13].

Early stent designs had high fracture rates, but the NuMED CP and covered CP stents have shown excellent long-term results with very low fracture rates [14]. The procedure uses femoral access, with the wires (sometimes Teflon-coated) usually crossing the coarctation retrogradely, but antegrade crossing from a radial approach and snaring the wire in the descending aorta can be needed in near atresia. Care needs to be taken to ensure the guidewire passes through the coarctation and not a collateral artery, as dilating a collateral will have a poor outcome.

A stiff guidewire is passed from the right femoral artery into the right brachial artery, via the left brachiocephalic, or into the ascending aorta. A long sheath is placed beyond the coarctation. The balloon and stent complex is advanced within the sheath through the coarctation and the sheath is backed out to well below the narrowing. Angiography in two planes allows accurate positioning. We use a NuMED balloon-in-balloon system (BIB), where the shorter, smaller inner balloon is inflated first, avoiding the stent sliding off the balloon due to one end of the balloon inflating first, creating an Eiffel Tower-like shape.  Pacing is rarely needed but forward blood flow means that active control of the balloon is needed to avoid distal migration.

Native coarctation and recoarctation following surgery are both amenable to stenting. Native coarctation requires lower balloon pressures, and usually gives better results than stenting a recoarctation. Modern high-pressure balloons and covered stents permit treatment of the majority of coarctation and recoarctation with low risk.  We have referred fewer than 2% of adult coarctations for surgery in the last 20 years.

Treatment of coarctation-related aneurysm requires a different approach. Our preference is to use self-expanding covered stents such as the Valiant (Medtronic), or the GORE TAG. These are more flexible in a fragile aorta, have very good sealing and allow the covered stent to seal the healthy aorta on either side of the aneurysm.  Our experience is that stent grafts did not cause increased gradients.  Side branches, such as the left subclavian artery, could retrogradely fill an aneurysm sac, so these can be occluded with vascular plugs, surgical ligation, or anastomosis of the left subclavian to the left carotid artery [15].

Pulmonary arterial stenosis

Treatment of pulmonary arterial stenosis is with PA angioplasty and stenting [16]. This is less commonly needed in adults than in children. The indication will usually require elevated RV pressure or reduced relative pulmonary flow to lung segments [17]. MRI flow or nuclear medicine perfusion scanning should be undertaken to document the physiology, whilst magnetic resonance angiography (MRA) and computed tomography (CT) show the anatomy well.

PA angioplasty can be successful, particularly if the stenosis is related to scar or fibrosis. Stenting uses a similar technique to coarctation with a long sheath protecting the balloon and stent during positioning. Purpose-designed delivery systems, improvement in sheath technology and stents with lower profiles are areas for development.

The course of the coronary arteries and the structures adjacent to a PA stenosis should be identified.  Some PA stenoses may require dilatation with a high-pressure balloons or require a cutting balloon predilatation, particularly in pulmonary atresia.

Pulmonary valve

Pulmonary valvoplasty

Pulmonary valvoplasty is first line treatment for children and adults presenting with PV stenosis. In adults there can be right ventricular outflow tract (RVOT) obstruction secondary to right ventricular hypertrophy (RVH), which often resolves after valvuloplasty [18], and is not a contraindication to valvuloplasty, neither is some regurgitation. Extreme forms of muscular RVOT obstruction may require surgery.  Percutaneous valve therapy can be used if valvuloplasty fails to relieve the valvar gradient or causes severe regurgitation.

Access is from the RFV, and a wire is placed in the distal PA, often using a balloon-tipped catheter to avoid tricuspid valve damage.  A compliant balloon is used, such as Cristal (Bard Medical) or NuCLEUS (NuMED). The balloon-to-annulus ratio often needs to be 1.2 or more. The valve is imaged with angiography and a multitrack monorail angiographic catheter documents the position of the pressure gradient. When the balloon is inflated it initially has a waist and then opens suddenly to achieve parallel sides.  The valve is reassessed for gradient and regurgitation.  It can be repeated with a larger balloon.  Occasionally a double balloon technique is needed but with the availability of 28-30 mm balloons this is now rare. A successful pulmonary valvuloplasty can give a long-lasting result, especially in young adults.  The procedure can be repeated even in older adults [19]. Severe pulmonary regurgitation rarely causes acute haemodynamic problems.  This is a mature technique that is unlikely to change.

Percutaneous pulmonary valve implantation

The first transcatheter valve implanted into a human was in June 2000 by Philip Bonhoeffer in Paris with a NuMED 34 mm CP stent with a bovine jugular vein valve sutured within it, two years before the first human TAVI [20]. This valve became the Medtronic Melody valve and was initially implanted into surgically placed conduits, such as homografts and other conduits between the RV and PAs. Being of venous origin the valve works over a wide range of diameters.

Video 1. (Videoclip courtesy of Professor Philipp Bonhoeffer)

The upper three images show a Melody valve being hand-crimped onto the Ensemble (Medtronic) delivery system. The lower left image is the progressive inflation of the balloon-in-balloon system, the middle image the valve en face under test and the final angiogram showing the stainless-steel pre-stent and the platinum-iridium stent (appears darker) of the Melody valve with no regurgitation.

Any patient with a conduit from the RV to the PA appeared suitable, such as post-operative Tetralogy of Fallot, Ross procedures and pulmonary atresia patients.   Initially we observed stent fractures within the CP stent in up to 25% of cases, but pre-stenting of the conduit to make a protected “landing zone” reduced the fracture rate [21] and became standard of care. Procedural mortality was reported at 0.3% [22]. Conduit rupture and coronary compression are the most feared complications.  Conduit rupture can sometimes be managed with supportive treatment and reversal of anticoagulation, or with covered stents. However, coronary compression usually required surgical treatment, and has been reported to cause procedure-related death. The maximum size of the Melody is limited, with the largest delivery system having a 22 mm balloon and the outside of the balloon and valve complex being around 24 mm. 

The SAPIEN (Edwards Lifesciences) valves can be used in the pulmonary position, for larger conduits and some non-conduit “native right ventricular outflow tracts” where some of the circumference of the annulus or main pulmonary artery (MPA) is made of autologous tissue, such that it can be pulsatile and distensible. The SAPIEN 3 29 mm valve can be dilated up to 30.5 mm (outer diameter) and can be implanted into 10-zig CP stents allowing treatment of nearly all conduits, and many “native outflow tracts” including those with a transannular patch.  The SAPIEN valve has pericardial leaflets, which work best when at nominal size. 

More recently, self-expanding systems have been developed to treat even larger RVOTs. The first-in-human self-expanding percutaneous pulmonary valve implantation (PPVI) was undertaken in 2006 [23]. This prototype became the Medtronic Harmony and was approved by the FDA.  The Chinese-designed P-Valve (Venus Medtech) is a self-expanding nitinol valve approved for use in Europe and capable of treating some patients with RVOT and MPAs of 36 mm or even greater.  Edwards Lifesciences has a device, the Alterra, for large pulsatile outflow tracts that uses a self-expanding pre-stent to reduce the diameter of the landing zone allowing a 29mm Edwards SAPIEN 3 valve to be implanted.  All three of these technologies are promising and have good initial results. There has been some concern about ventricular arrhythmia when the self-expanding components are in contact with the muscular RVOT.  The arrhythmia appears transient but remains a cause for concern.

IE has been the main concern in the PPVI experience.  It has been shown that leaving residual gradients after PPVI, commonly in small conduits, predisposes to IE [24]. Initially the Melody valve was considered the culprit, but Melody is most commonly used in small homograft conduits, where IE is most likely. We minimise residual gradients by aggressive pre-stenting and dilation with high pressure balloons. If transcatheter valves are implanted into a stented tissue valve, we aim to over dilate or “crack” the surgical ring where possible to minimise gradients and turbulence, thus minimising IE risk. Self-expanding valves appear to have a low rate of IE, despite there being a large amount of prosthetic material, perhaps because of low gradients, and are rarely implanted into conduits.

PPVI was initially seen as a way to reduce the number of sternotomies that a patient may need in their lifetime but has now become first-line therapy.  Infective endocarditis rates appear to be similar to those of surgical PVs [25]. Once the self-expanding valves are widely available, the majority of PV problems will be treated percutaneously, with endocarditis or risk of coronary compression remaining the main indications for surgical treatment.

Aortic valve   

Aortic valvuloplasty

Aortic valvuloplasty is the standard of care for neonatal and childhood aortic stenosis and can be used through to middle-aged adults [26]. It is probably underutilised, especially for young women wanting to avoid having a mechanical valve during pregnancy.

In small children axillary artery access is used, but femoral artery access is preferred for older children and adults. The valve is crossed retrogradely with a guidewire, then a supportive exchange-length guidewire is introduced into the left ventricle. In adults we use wires with a looped end such as the SAFARI (Boston Scientific) wire. A balloon-to-annulus ratio of 0.9-1.0 is most common but can reach 1.2.  High pressures are not usually needed, so many operators use a syringe rather than an indeflator to avoid unnecessarily high pressure.  Relatively compliant balloons similar to pulmonary valvuloplasty are usually sufficient to achieve a good result, and it can be repeated with a larger balloon if needed.

Transcatheter aortic valve implantation

TAVI has revolutionised the treatment of aortic stenosis (AS) in elderly patients with degenerative disease, especially where a surgical valve replacement is high risk. We have previously reported the feasibility of using TAVI for adult CHD [27] as these patients have frequently had prior surgery so may also be at high risk for further surgery.

We have used TAVI to treat a number of younger patients with AS showing feasibility of treating various anatomic substrates, including bicuspid valve in a Fontan circulation [28], aortic homografts (where reoperation is especially difficult), a patient with congenitally corrected transposition of the great arteries and a range of post-surgical aortic valve problems.  Retrograde access has been possible through native coarctation, surgically repaired coarctation, and stented coarctations.

Surgeons argue that surgical pericardial valves last longer, but a meta-analysis shows that TAVI valves are just as durable as pericardial leaflet surgical valves and display lower gradients [29]. Pacemaker rates are higher in TAVI, but pacing rates are higher in some forms of redo-cardiac surgery. 

TAVI is not suitable for all adult congenital patients requiring aortic valve intervention, but it should be considered an option and not simply be dismissed because it was designed for older patients.

Additional techniques

Transcatheter paravalvular leak occlusion is a standard technique in acquired heart disease with dedicated devices, such as the Abbot microwave nitinol Amplatzer Vascular Plug III.  Congenital patients can also suffer paravalvular leakage and benefit from this technique. 

Edge-to-edge repair of mitral and tricuspid valves can be applied to congenital patients, even those with single atrioventricular valves.

We developed a technique to occlude false aneurysms, where we combined nitinol wire plug occlusion with coiling of the aneurysm behind the plug. We have also applied this to congenital patients [30].

Impact on practice

In the last 25 years, percutaneous transcatheter procedures have revolutionised the treatment of some adults with CHD.  Advances in equipment design, preprocedural imaging, vascular ultrasound guidance and improved technical skills of the operators have permitted percutaneous treatments to become the standard of care in many conditions, improving the lives of countless patients. The imagination and commitment of the engineers and operators appears undiminished, so there is no reason to expect that the rate of development will slow down.