We’ve discussed cryoplasty before in Vascular News and it was no surprise that this cooling procedure for clearing blocked arteries was one of the hot topics at the International Symposium on Endovascular Therapy (ISET) 2003 in Miami.
The first clinical trials with cryoplasty were initiated in 2001 for superficial femoral artery (SFA) disease, with initial data being presented at ISET 2002. In this first-in-man (FIM) study, 12 patients with SFA/political disease were successfully treated with stand-alone cryoplasty. Angiographic follow-up at 6–9 months demonstrated 0% binary restenosis. At ISET 2003, James Joye, Director, Peripheral Vascular Interventions at the Cardiovascular Institute, El Camino Hospital, Mountain View California, provided an update on the results of this FIM study. Angiograms for the first 12 patients treated with cryoplasty in SFA and popliteal arteries showed that 10 of the 12 looked virtually unchanged from immediate post-procedure, and the restenosis rate was 16%, said Joye.
However, the primary focus of the ISET 2003 cryoplasty presentations was the start of the US IDE study (principal investigators: John Laird, Washington Hospital Center, Washington, the US, and Giancarlo Biamino, Director of Clinical Interventional Angiology at Herzzentrum, Leipzig, Germany) in the SFA and popliteal arteries. This concluded enrolment in mid December and, according to Joye, to date shows a restenosis rate of around 12% in what are fairly complex lesions. “Nearly 20% of these were chronic occlusions, a large number were calcified lesions at the adductor hiatus (a notoriously difficult target), and most had limited runoff (known to further limit the success of conventional approaches to the problem). A historical comparison would estimate a restenosis rate of over 50% in the same population of patients,” said Joye
The next major update on this study will be presented at the ACC and SIR meetings later this year. Final data should follow at TCT this autumn. At this stage, the initial data should be interpreted cautiously as restenosis often occurs after six months. So definite proof that cryoplasty is effective in the long term has not yet been obtained.
One benefit that has been shown by this study is a lower significant dissection rate for cryoplasty compared with conventional PTA. The rate of significant dissection with conventional PTA is around 40-45%, which has led to a higher use of stents. Despite stenting the restenosis rate remains around 50%. Joye stated: “Cryoplasty has reduced the rate of meaningful dissection to around 6%. This dramatic change eliminates the need for routine stenting and achieves similar acute results without a foreign body implant.”
The main difference between cryoplasty and angioplasty is that in cryoplasty the balloon is inflated with pressurised nitrous oxide instead of the saline used in angioplasty. The nitrous oxide cools to a temperature of minus 10 degrees Celsius, which freezes the plaque and induces apoptosis.
The device used to perform cryoplasty is a disposable instrument made up of three components: a cryoinflation unit, a catheter and a nitrous oxide cartridge.
The cyroinflation unit is a small hand-held device that is pre-programmed to deliver the therapy while monitoring temperature and several parameters that are designed to ensure patient safety during the procedure. The main product in this area is the PolarCath System, developed by Cryovascular Systems, which received FDA clearance last September for treating clogged leg arteries, opening the way for potential widespread use of this technique in the US. (It already has CE approval and has been launched in several European countries)
The interventionalist uses standard percutaneous angioplasty techniques to place the catheter via femoral artery access. Once this is accomplished, the catheter is connected to the cryoinflator and a cartridge of pressurised liquid nitrous oxide is then inserted into a receptacle in the cyroinflator, secured in place, and the start button is pressed. The balloon has radiopaque markers indicating the treatment length/zone. Total treatment time is less than one minute and multiple treatments are possible.
Clinical trials suggest that the cryoplasty technique is gentler on the artery wall than angioplasty, leading to much of the inflammation and scaring that contribute to restenosis being prevented. This result was anticipated as cryosurgical studies performed over 30 years ago confirmed that a benign healing process largely devoid of neointimal proliferation followed freezing arterial tissue in vivo (Gage, et al.). Cryoplasty appears to alter the morphology of collagen fibres in a way that limits the recoil but does not impair the conduit function of the artery.
Dr Joye believes that there are many other possible applications for cryoplasty in the vascular field. Joyce said: “We are investigating coronary applications for native coronary areas, bypass grafts and for vulnerable plaque treatment. In the peripheral arena we are exploring applications for limb salvage and dialysis graft treatment to name a few.”
One concern over cryoplasty is its anticipated cost compared to other procedures. “A cryoplasty balloon will certainly cost more than an existing PTA balloon. However, by contrast, it will cost significantly less than a drug-eluting stent,” explained Joye.
Joye contends, “In the real world, as at least half of lesions are dilated and stented, the cost per procedure is actually significantly less with cryoplasty” He added, “The more complex the lesion, the greater the cost advantage, because instead of the incremental cost of each successive stent, cryoplasty has a nominal cost associated with each inflation”. As an example he stated, “ A 30cm lesion in the SFA would require roughly two PTA balloons and four stents at a cost of around $9,000 dollars. If these are changed to drug-eluting stents, then the cost will be a minimum of $18,000. In contrast cryoplasty would cost only $2,500 for the whole procedure.”
In conclusion, cryoplasty may offer something that can exceed the success of uncoated or drug-eluting stents. This is without a permanent implant and without the high cost associated with drug-eluting stents. Nevertheless there is a concern that the technique is more expensive than traditional angioplasty techniques, which may hinder its adoption when conventional PTA is possible. “Given what we have seen it is difficult to justify conventional PTA when cryo is available because the results are that much better…given the dramatic improvement in results the cost of the cryoballoon will be easily justified”, said Joye. In addition, although clinical trials have been successful up to now, further data on long-term restenosis rates are needed.