History and Literature Review

ACI Medical observed significant increases in arterial blood flow while testing a device that applied rapid, high level compressions to the lower limb. Excited by these findings, ACI identified the following goals: 1. Determine the mechanisms of action that produced this phenomenon, 2. Define the optimum stimulus for maximizing blood flow to ischemic tissues, 3. Measure the physiological effects on arteriopathic patients, 4. Study the clinical effects on patients with intermittent claudication and 5. Determine its clinical utility for limb salvage in patients with critical limb ischemia. ACI worked with academic centers in the US, UK, Canada and Ireland to reach these goals.

 

Following is a summary of the published literature and most recent studies in press.

van Bemmelen et al investigated the effect of rapid, intermittent calf compression on popliteal arterial flow using color duplex ultrasonography. They found that using pressures of about 100 mmHg applied to the dependent limb of arteriopathic patients approximately tripled popliteal artery flow. Not only was peak systolic increased but end diastolic flow was as well which suggests a significant decrease in peripheral resistance. He suggested that two physiologic mechanisms contributed to the hyperemic response: Emptying of the veins under the cuff dropped their venous pressure to almost zero while not affecting the arterial pressure. The arterial to venous pressure gradient was therefore increased and flow increased by a similar factor. Second, since the cuff is inflated rapidly (appx. 0.3 seconds rise time), the high shear rate causes the endothelium to release nitric oxide (NO), a powerful vasodilator.

Investigations by Eze, Comerota et al from Temple University showed that rapid, high pressure IPC not only increased popliteal artery flow (using duplex imaging) but also significantly increased foot skin perfusion using laser Doppler fluximetry. We learned the importance of compressing both foot and calf regions in that they both contributed to enhancement of popliteal arterial flow and cutaneous flow at the foot.

Understanding that reduction in venous pressure was an important mechanism of action, Delis and Azizi et al performed an optimization study that measured invasive foot vein pressures. They determined the optimal stimulus that was then incorporated into the device used in future clinical testing and the commercial device: foot, followed by calf compression to 120 mmHg in 330 msec rise time and fall time with 3 second pressure hold, 3 times per minute.

van Bemmelen et al continued their research with the optimized device and showed the significant increase in skin circulation using laser Doppler fluximetry in patients with infra-popliteal disease. He also showed Angiographic evidence of another mechanism of action: the formation of collateral arteries that takes place after several months use of the ArtAssist device. Further work on rabbits showed that collateralization is indeed an important, long-term mechanism of action.

Labropoulos et al measured arterial flow in the popliteal artery, medial gastrocnemial artery, genicular collateral artery and skin blood flow of the foot in patients with critical limb ischemia shown by arteriography. Flow was increased significantly in all measured vessels and cutaneously even in end stage ischemic disease.

Delis’ randomized, controlled trial (RCT) studied patients with intermittent claudication who are not usually candidates for surgical intervention. His group found that after 5 ½ months of ArtAssist device therapy, patients experience a tripling in pain free walking distance, increased arterial pressure at the ankle (most likely due to collateralization) and improved quality of life. These improvements were sustained for at least a year after therapy further supporting the mechanism of collateralization. The control group had no such improvements.

Ramaswami’s RCT on patients with intermittent claudication showed too that the significant increases in pain free walking distance were sustained after one year.

This was a three-arm RCT of ArtAssist compression, supervised exercise and unsupervised exercise done by Kakkos, et al. They showed almost tripling of pain free walking distances and increased ankle pressures in intermittent claudication patients in the ArtAssist device group and supervised exercise group while no benefits were observed in the unsupervised exercise group.

van Bemmelen et al were the first to examine the possible impact of ArtAssist device compression in limb salvage of critically ischemic limbs. Patients that used the device at least 2.4 hours per day showed improved arterial pulsatility and limb salvage compared to those that used the device for only about an hour per day. This study set the stage for additional limb salvage trials by Louridas and Esan.

Louridas, et al performed a pilot study to determine if ArtAssist compression was efficacious in preventing amputations in critically ischemic limbs that were unsuitable for surgical revascularization. Encouraging results supported the larger, RCT using a placebo device. With a 24 month follow-up, the ArtAssist device group had an 86% limb salvage rate in non-renal failure patients compared to a 32% limb salvage rate for the control group.

Esan et al performed a limb salvage trial with a one-year follow-up. Their limb salvage rate of 88% was similar to Louridas’ 86%. They also showed that rest pain was relieved in less than a week and that ArtAssist compression reduced hospital stay and imparted significant cost savings.

At the Mayo Clinic, Kavros et al studied 48 patients with ischemic ulcers, using a similar device that only applied calf compressions at lower pressures. Their limb salvage rates were inferior to the ArtAssist device’s results: 58% limb salvage in the experimental group and 17% in the control group. However, these significant results from a well-respected group support the concept of using this modality as adjunct therapy for limb salvage in critical ischemia.

The ArtAssist compression device is a home use treatment for patients with peripheral arterial disease. Recommended usage is 3 to 6 hours per day for 90 days. The mechanisms of action including arterial collateralization have been well identified. The device parameters of pressure, timing and compression locations to include the foot and calf have been optimized for PAD. It is shown to be effective in increasing pain free walking distance in claudicants for a sustained period in three independent studies. It has been shown to prevent amputations in critically ischemic limbs in three independent studies. This treatment modality is well tolerated, has no known adverse reactions and represents a cost effective alternative to other medical and surgical interventions.