Despite the recent introduction of vascular closure device (VCD) technology, vascular access site complications remain the leading source of morbidity and costs after the approximately eight to eight-and-a-half million percutaneous catheter-based procedures performed annually worldwide.1 VCD trials consistently demonstrate increased patient satisfaction, early ambulation, and decreased hospital resource utilisation compared with manual compression (MC).2,3 Unfortunately, these reports have not consistently demonstrated decreased complication rates, and current VCD technology has even created a new category of complications and treatments primarily involving infection and arterial thrombosis.4-9
In 1953, Seldinger classically reported the original description of percutaneous femoral artery (FA) access and, in so doing, first reported vascular access haemostasis (VAH).10 Since then, significant technological advances in the field of catheter-based cardiovascular (CV) therapy have rendered most early percutaneous technology obsolete. It is remarkable that, 50 years later, the gold standard of VAH remains MC, performed almost exactly as Seldinger originally described, '20-30 minutes hand-held pressure after catheter removal followed by overnight bed rest.'10 This gold standard remained largely unchallenged over the next four decades, until the widespread adoption of percutaneous CV interventions. These procedures require larger sheaths and more potent anticoagulation, increasing the clinical potential for complication.
The Problem Exposed
FA access complications (FAC) remain a significant source of mortality and are the leading cause of morbidity and costs after percutaneous coronary intervention (PCI).10-12 Remarkably, no standardisation exists with regard to reporting 'major' and/or 'minor' FAC rates, which vary widely from 0.4% to 27% depending on the definition of complications.7-9,12 Most reports site only 'major' FACs requiring surgery, and it is highly likely that many FACs go unreported or are accepted as 'part of the territory' (see Figure 1). Duffin et al.3 were among the first to identify FACs as a major problem, noting a 14% bleeding rate with PCI. In a randomised trial comparing MC with AngioSeal (St Jude Medical, St Paul, MN), Kussmall et al.11 reported a 27% overall 'any complication' rate in the MC group with heparin. In 2001, Danges et al.5 compared MC (n=4,596) with VCDs (n=497) after PCI and reported higher 'overall complication' rates with VCDs versus MC (21.4% versus 12.1%, respectively), again confirming significant 'overall complications' with MC and identifying that current VCD use may increase complications.
Pracyk et al.12 cited a 64% overall FAC rate with MC when patients were thoroughly scrutinised by physical examination and duplex ultrasound. A review of the literature reveals sparse data on MC with regard to a haemostatic mechanism, healing or scarring of the arteriotomy site, short- or long-term FA clinical sequelae, systemic effects of a groin haematoma, or a consensus recommendation on the safety, risks and timing of FA re-entry. After 50 years of truly remarkable CV technological achievements, it seems reasonable to ask whether MC should still be the gold standard, and why.
FAC - Clinical and Economic Costs
Aguirre et al.13 found FAC increased the length of patient stay to an average of 3.5 days compared with <2 days in an uncomplicated PCI. Moscucci et al.14 suggested that FAC may indirectly increase ischaemic complications after PCI when they reported the incidence of death and myocardial infarction (MI) among patients with FAC as 2.4% and 13%, respectively, versus 0.2% and 3.0% in 4,090 PCI patients without FAC (p<0.0001). Extrapolating financial costs to FAC is difficult, but in tracking blood transfusions after PCI, Lauer et al. estimated a single unit of blood transfusion during PCI adds an additional US$8,000 to the overall cost of that hospitalisation.15,16 The Replace-2 study has now shown increased 30-day and one-year mortalities in PCI patients who experience a bleeding complication and increased morbidities (MI, need for repeat PCI, etc.).17
Limitations of Current VCD
Currently, it is estimated that only 20-25% of all catheter-based procedures performed worldwide utilise a VCD for access site haemostasis.1,2 Several potential limitations associated with current technology that limit widespread clinical VCD utilisation are summarised in Table 1.
Percutaneous Staple Technology
Surgical metal staple technology has revolutionised traditional general, vascular and cardiothoracic surgery for several decades and has proven safe, biocompatible and cost-effective. The Vascular Closure System (EVS) closure device (Angiolink Corporation) was specifically designed with the goal of being the ideal VCD by addressing the limitations of current VCDs utilising well-known surgical and endovascular concepts, including biocompatibility, sterility, simplicity and the 'anatomic purse-string effect' to achieve immediate, safe, secure and cost-effective extraluminal femoral arteriotomy closure.9
The Angiolink Staple
The device consists of three components:
- A low-profile, 3mm biocompatible titanium staple (see Figure 2) designed for deployment 1mm above the vessel adventitia, and four staple legs, each with a distal 'pledget-flare' designed to gather an 'autogeneous tissue pledget' of femoral sheath, adventitia and media for an autogeneous extraluminal closure (see Figure 2).
- A simple one-piece 'three-step' introducer assembly containing an introducer, a dilator with a blood-marking lumen positioned 7mm from the distal tip, and two small 'stabilisation filaments' designed to transiently deploy intraluminally, maximising vessel wall stabilisation for staple deployment (see Figure 3).
- A trigger-activated staple deployment device (see Figure 3). The staple and stapler utilise a unique proprietary deployment cycle design that allows initial staple expansion and advancement to gather autogeneous tissue prior to final staple closure, achieving an 'anatomic purse-string' (see Figure 3).
The arterial sheath is removed and the dilator and introducer are introduced over a 0.035-inch guidewire through the overlying tissues until brisk bleeding is noted from the distal dilator port marking the depth of the arterial lumen. The guidewire is removed and the 'three-step' introducer maneuver is performed, stabilising the anterior vessel wall. The dilator is then removed and the staple device is advanced through the introducer until the stapler reaches the level of the stabilised anterior vessel wall where the system locks itself in place, which can be noted by an audible 'click'. The staple, still housed sterile in the deployment device, is now located 1-2mm above the adventitia. As the trigger is activated, the staple deployment cycle is performed, the stabilisation filaments are retracted, and the introducer is removed all in the same final movement, having deployed the completely sterile staple to the arteriotomy site (see Figure 3).
Achieving the 'Ideal VCD'
Titanium has become the most common human metal implant material because of its superior properties of strength and pliability, biocompatibility and inertness, and cost-effectiveness compared with stainless steel, making it ideal for the intricate Angiolink staple design. Permanent braided sutures, collagen plugs, and other absorbable procoagulants used with current VCD are non-inert, highly reactive, and may be an aetiologic factor in infection and arterial thrombosis.
The one-piece introducer assembly system has been designed for simplicity, uses cost-effective materials, and has a short learning curve. The staple remains sterile within the stapler 'housing' and introducer until final deployment inside the body at the extraluminal vessel wall - much like the sterile deployment of a stent, therefore avoiding operator or skin contamination. The entire system is designed for single-operator use and, with experience, the total operator closure time should be less than 60 seconds.
The 'purse-string suture' closure concept is a well-known surgical technique used to close large arteriotomies in large vessels, with the most notable being decannulation of large-bore cannulas from the ascending aorta during cardiac surgical procedures. The technique utilises pledgets to gather only vessel adventitia and media at the arteriotomy edges, allowing for tissue approximation when the cannula is removed and the suture is tied. This results in immediate, secure, totally extraluminal vessel closure in the anticoagulated patient with pulsatile aortic blood flow. This extraluminal closure is accomplished without luminal narrowing and, therefore, this device theoretically could be utilised in any vessel regardless of 'stick' location, size or anticoagulation status and could allow almost immediate ambulation.
The Angiolink Trial
The Angiolink pivotal safety and efficacy study and 30-day follow-up was completed in the first quarter of 2004. This multicenter, prospective, randomised trial was challenged by the US Food and Drug Administration (FDA) with higher standards than previous VCD trials by requiring >50% coronary and peripheral interventions, therefore larger sheaths (7-8Fr) in heavily anticoagulated patients. The pivotal trial results are shown in Table 2. The in-hospital major complication rate was 0.4% for Angiolink and 1.7% for MC. The 30-day major complication rate was 0.4% for Angiolink versus 2.5% for MC, therefore the Angiolink pivotal trial became one of the only VCD trials that has demonstrated fewer complications than the gold standard, MC. The pivotal trial confirmed the simplicity of the device by showing a mean total time to staple deployment of 1.3±2.2 minutes. The learning curve likewise proved simple as demonstrated by physicians requiring only a mean of 2.4 'roll-in' deployments before they felt they were trained and began trial enrollment. A subanalysis of the Angiolink pivotal trial on peripheral vascular disease (PVD) interventional cases was presented at the prestigious Transcatheter Cardiovascular Therapeutics (TCT) meeting in September 2004 in Washington DC. Pertinent findings of that PVD subanalysis include statistically significant improved time to haemostasis (TTH), time to ambulation (TTA), and major and minor complications in favour of the Angiolink versus MC group in the high-risk PVD patient with >80% receiving IIbIIIa anticoagulation in each group.
The Future Potential
Just as metal stent platform technology has revolutionised interventional CV care, and metal staple technology has revolutionised traditional surgery, there is this same revolutionary potential for catheter-based treatment and femoral access site management. Future designs of this device can be engineered both smaller and larger, and could accommodate >20F sheath sizes, making abdominal and thoracic aortic aneurysms and other larger sheath-based interventions (PFO, percutaneous hearts valve, etc.) totally percutaneous. Totally absorbable inert surgical staple technology already exists, and an absorbable Angiolink staple could easily address any concerns regarding re-access or re-entry with this first generation staple technology. The soon-to-be-released second generation Angiolink device will be lower profile and even easier to deploy by being compatible with the existing smaller sheath, therefore eliminating the introducer sheath.
VCDs were initially designed to achieve convenience for the patient and hospital and this has largely been achieved in the 20-25% of currently treated patients. This has likely been achieved at an increased complication rate with current VCDs. The Angiolink staple has the potential to make a VCD a powerful clinical treatment tool that can be utilised in all aspects of case management to truly effect clinical care and clinical decision-making. Immediate, safe, secure management of the femoral access site could potentially affect clinical decisions on endovascular treatments (larger sheaths, stentgrafts, new devices, etc.), periprocedural anticoagulation management (Coumadin, IIbIIIas, thrombolysis, etc.), staging procedures and hospital discharge. The current Angiolink staple has been designed to address the limitations of current vascular closure technology and, therefore, may have the potential to significantly increase clinical VCD utilisation. When the ideal VCD becomes available, there would be no reason not to use it on every procedure in every lab, worldwide.