Traditional treatment for complex lower extremity arterial occlusive disease has often included surgery, but development and improvement of other treatment alternatives has resulted in their application in these procedures as well. The question still remains: which of these alternatives will stand the test of time and replace other treatment options? I present an array of infrageniculate and dialysis access cases in which CryoPlasty Therapy (Boston Scientific Corporation, Natick, MA) was the primary modality for treating the lesions.

CASE REPORTS
Case 1
The patient was a 70-year-old man with debilitating bilateral claudication of the lower extremities (Rutherford category 3) and a history of coronary artery disease and hyperlipidemia. Noninvasive studies showed an ankle-brachial index of 0.6 and duplex findings of mostly calcific occlusive disease of the femoral arteries bilaterally (Figure 2A). Arteriography of the left lower extremity revealed focal calcific plaque with an occlusive lesion of the left common femoral artery (CFA) (Figure 1A). Selective access to the left proximal CFA was obtained via the right CFA using a Pinnacle Destination Sheath (Terumo Interventional Systems, Somerset, NJ). The left CFA occlusion was crossed with a Fathom® Guidewire (Boston Scientific Corporation). The lesion was predilated with a 3-mm Sterling® Balloon (Boston Scientific Corporation) (Figure 1B) and then treated with an 8- X 40-mm PolarCath® Balloon (Boston Scientific Corporation), which provided an excellent arteriographic result (Figure 1C). This was followed 3 weeks later by similar treatment of the right CFA occlusion. The patient had immediate resolution of the symptoms with no evidence of recurrence. Eighteen months later, the patient remained symptom free, and noninvasive examination of the CFAs bilaterally showed no evidence of plaque recurrence (Figure 2B).

Case 2
A 98-year-old woman with a history of coronary artery disease, hyperlipidemia, and hypertension presented with gangrene of the left first and fourth toes with noninvasive studies showing ankle-brachial indices of 0.37 and 0.42 on the right and left sides, respectively. With no surgical options available to treat this elderly woman, the decision was made to perform arteriography of the left lower extremity. Access to the left lower extremity was obtained via the right CFA. Arteriography of the left lower extremity revealed generalized calcific plaque of the entire left lower extremity arterial tree with multisegmental disease of the left superficial femoral artery (SFA) (Figure 3A) followed by complete occlusion of the left popliteal artery (Figure 3B). The only runoff to the leg was with a reconstituted peroneal artery via lateral geniculate collaterals. Selective access to the left SFA was obtained via the right CFA using a Pinnacle Destination Sheath. The left SFA multisegmental disease was treated with a 5- X 100-mm PolarCath® Balloon, which resulted in an excellent arteriographic result (Figure 3C). The left popliteal artery occlusion was crossed with a Fathom® Guidewire and a 3- X 40-mm Sterling® Balloon. The true lumen gain was confirmed with arteriography, and the lesion was predilated with the Sterling Balloon. The vessel was then treated with CryoPlasty Therapy of the popliteal artery with a 5- X 60-mm PolarCath Balloon. Runoff showed brisk flow in the left peroneal artery (Figure 3D) with reconstitution of the left anterior and posterior tibial arteries via collaterals from the left peroneal artery (Figure 3E).

The patient had immediate resolution of rest pain with healing of the ulcers and gangrenous areas. The patient was discharged home later that day. Nine months later, she remained symptom free, and noninvasive examination of the left popliteal artery showed no evidence of plaque recurrence.

Case 3
A 48-year-old man with long-standing type I diabetes mellitus, coronary artery disease, and end-stage renal disease underwent arteriovenous fistula creation at the wrist in the form of radiocephalic fistula. Two years after fistula use, the patient was noticed to have poor dialysis sessions, and noninvasive duplex imaging showed high-grade stenosis of the fistula just distal to the radiocephalic anastomosis. A fistulagram was obtained via a right brachial artery cutdown, and brachial artery access was obtained via a 7-F sheath. A fistulagram obtained via a sheath in the radial artery showed a near occlusive lesion of the proximal segment segment of the fistula (Figure 4A). The lesion was crossed using a Fathom Guidewire (Figure 4B) and predilated with a 3- X 40-mm Sterling® ES Balloon. The lesion was definitively treated with an 8- X 40-mm PolarCath Balloon. The follow-up fistulagram showed an excellent arteriographic result (Figure 4C). The patient was able to resume dialysis immediately thereafter, and follow-up surveillance duplex showed no evidence of recurrent lesion. The patient was still dialysis-symptom free and intervention-free at 24 months.

DISCUSSION
In my experience, percutaneous procedures for peripheral artery occlusive disease have generally exhibited inferior patency rates when compared to surgical treatments; however, surgical treatment has demonstrated its own drawbacks. The abundance of available endovascular treatments has led me to one conclusion: none of them are perfect yet. Balloon angioplasty for infrainguinal arterial disease can be successful but can also lead to procedural challenges like arterial wall dissection, recoil, recurrence, and treatment failure.

Traditionally in case 1, I would have suggested surgical treatment in the form of femoral endarterectomy. In case 3, the repair of the fistula with vein patch angioplasty would be certainly considered a premier treatment option. I believe that offering endovascular treatment options to patients without potentially compromising future surgical interventions, should they be needed, has a definitive place in the treatment of vascular disease.

CRYOPLASTY THERAPY
CryoPlasty Therapy combines angioplasty with cold therapy via the PolarCath® Peripheral Dilatation System. The PolarCath Peripheral Dilatation System incorporates nitrous oxide as a dilation medium. Widespread use of nitrous oxide in other medical applications eventually prompted its use in arterial interventions, and it is soluble in the vascular system. The release of nitrous oxide from liquid form to gaseous form results in volume expansion, exhibiting cooling in accordance with the law of energy conservation. CryoPlasty Therapy is designed to deliver temperatures of -10°C at the interface of balloon and intima. This low temperature theoretically may induce apoptosis in the vessel wall.

The PolarCath® Peripheral Dilatation System consists of several integrated components: a PolarCath Balloon catheter, the PolarCath® Inflation Unit, nitrous oxide canisters, and a power module. The PolarCath Balloon is outwardly similar to a conventional angioplasty balloon but it is composed of three layers. The inner balloon contains the nitrous oxide gas and maintains the pressure, allowing the outermost balloon to expand passively. The middle layer contains a textile fabric that is designed to insulate the reaction for an accurate delivery of the desired outside temperature. A pattern of radiopaque markers is also inscribed on this fabric to allow for visibility under fluoroscopy, because nitrous oxide within the balloon is otherwise radiolucent (Figure 5). This space was engineered to create a vacuum during preparation of the balloon. The device is designed to continuously monitor this vacuum throughout the inflation and treatment cycles. Finally, the balloon also houses a thermocouple that is designed to constantly monitor the temperature and determine whether it is within the ideal working range.

The PolarCath Balloon inflation cycle is automated and regulated by the PolarCath Inflation Unit. This is a microprocessor- controlled device that integrates the PolarCath Balloon and the nitrous oxide cylinder. Once each of the three components is connected, activation of the device runs through a preprogrammed series of methods that test and monitor the device performance, nitrous oxide delivery, desired balloon dilation and cooling parameters. The balloon undergoes a 20-second controlled inflation up to 8 atm. Once the balloon reaches 8 atm, liquid refrigerant is cycled through the balloon catheter, bringing the outer balloon temperature to -10°C. This treatment cycle lasts 20 seconds, after which the balloon warms, the gas is evacuated, and the balloon may be deflated. Although the PolarCath Inflation Unit may be used for multiple inflations per patient, each PolarCath Balloon inflation requires a new nitrous oxide cylinder, allowing lesions to be treated with multiple inflations if desired.

MECHANISM OF ACTION
The primary theoretical mechanism of action for CryoPlasty Therapy is the induction of apoptosis (programmed cell death) in the intima and media, which may theoretically affect the restenosis process. In in vitro cell specimen studies, Tatsutani et al demonstrated conversion to an apoptotic life cycle in human smooth muscle and endothelial cell lines with exposure to temperatures of -10°C.1

It has been shown in in vitro cell specimens that freezing interstitial saline in the medial layer of the vessel wall can create a hypertonic environment. Applying this concept to CryoPlasty Therapy, it is theorized that after deflation and rewarming, free water that was forced out of the cells may re-enter the cells, which should re-establish isotonicity. It is believed that this intracellular dehydration and rehydration may induce apoptosis. If this occurs, isotonicity may maintain cell membrane integrity, which could potentially prevent systemic inflammatory response, theoretically modulating the neointimal response.

Fava and colleagues studied 15 patients with application of CryoPlasty Therapy in arterial occlusive disease and reported a 93% (14/15) technical success rate.2 Angiographic follow-up at 14 ± 4 months showed the primary patency rate to be 83% (10/12). Laird et al then reported initial safety data in connection with their multicenter registry of 102 patients with femoropopliteal disease with a wide array of disease processes.3 Technical success was reported as 94.1% (96/102) with a primary patency rate of 70.1% at 9 months by Doppler ultrasound (23/77) and a clinical patency rate of 75% by Kaplan Meier estimate at 3.4 years for the 70 patients followed to 3.4 years.4

In my experience, I have used CryoPlasty Therapy as the primary option in locations where I am unlikely to stent, such as common iliac arterial lesions, the CFA, the profunda femoris artery, ostial lesions, the popliteal artery, and the tibial arteries. In these locations, my use of CryoPlasty Therapy has preserved my options for future surgical treatment should they be needed. I have found long-length lesions of entire segments of arteries, such as the SFA, tibial arteries, and autogenous bypass graft and dialysis accesses, to be especially amenable to CryoPlasty Therapy. I have also found that treating complex lesions can require a combination of devices and strategies, including balloon angioplasty and debulking technologies.

Baljeet Uppal, MD, is a vascular surgeon with Our Lady of Lourdes Hospital in Binghamton, New York. He has received no financial compensation for participation in this supplement. Dr. Uppal may be reached at baljeet.uppal@gmail.com.

  1. Tatsutani KN, Joye JD, Virmani R, et al. In vitro evaluation of vascular endothelial and smooth muscle cell survival and apoptosis in response to hypothermia and freezing. CryoLetters. 2005;26:55-64.
  2. Fava M, Loyola S, Polydorou A, et al. Cryoplasty for femoropopliteal arterial disease: late angiographic follow-up of initial human experience. J Vasc Interv Radiol. 2004;15:1239-1243.
  3. Laird J, Jaff MR, Biamino G, et al. Cryoplasty for the treatment of femoropopliteal arterial disease: results of a prospective, multicenter registry. J Vasc Interv Radiol. 2005;16:1067- 1073.
  4. Laird JR, Biamino G, McNamara T, et al. Cryoplasty for the treatment of femoropopliteal arterial disease: extended follow-up results. J Endovasc Ther. 2006;13(suppl 2):II52-II59.

POLARCATH® PERIPHERAL DILATATION SYSTEM
Prior to use please see the complete “Directions for Use” for more information on Indications, Contraindications, Warnings, Precautions, Adverse Events, and Operator's Instructions.

INDICATIONS:
The PolarCath System is indicated to dilate stenoses in the peripheral vasculature (iliac, femoral, popliteal, infrapopliteal, renal and subclavian arteries) and for the treatment of obstructive lesions of polytetrafluoroethylene (PTFE) access grafts or native arteriovenous dialysis fistulae. The PolarCath System is also indicated for postdeployed stent expansion of self-expanding peripheral vascular stents.

CONTRAINDICATIONS:
None.

WARNINGS:
Use of this device in coronary or carotid arteries has not been evaluated. Use of this device for stent delivery has not been evaluated. Use of this device for non-PTFE access grafts has not been evaluated. It is unknown whether the cold temperatures generated by the catheter will have any adverse effects on the material integrity and long term performance of these non-PTFE grafts.

POTENTIAL ADVERSE EFFECTS:
Possible adverse events include but are not limited to the following:

  • Allergic reaction to contrast media
  • Arteriovenous fistula
  • Death
  • Embolism
  • Gas embolism
  • Hemorrhage/hematoma
  • Pain and tenderness
  • Pseudoaneurysm formation
  • Pyrogenic reaction
  • Restenosis of the dilated vessel
  • Sepsis/infection
  • Thrombus
  • Total occlusion
  • Vessel dissection
  • Vessel perforation

PRECAUTIONS:

  • A thorough understanding of the technical principles, clinical applications, and risks associated with percutaneous transluminal angioplasty is necessary before using this device.
    • Only PTFE arteriovenous graft material has been tested for compatibility with the PolarCath Dilatation System. To determine compatibility, testing was conducted to evaluate the tensile mechanical strength of PTFE samples treated with CryoPlasty® Therapy compared to those treated with conventional balloon angioplasty in a simulated environment. No difference was found between the two systems.

CAUTION:
Federal law (USA) restricts this device to sale by or on the order of a physician.