Intravascular Lithotripsy for Infrapopliteal Stenosis in Critical Limb Ischemia

Critical limb ischemia (CLI) is a life-threatening condition associated with significant morbidity and mortality. Within the first year of CLI diagnosis, death occurs in 25% of patients and 30% will have a major limb amputation.¹ Vascular calcification is present in many CLI patients, particularly in the elderly, diabetics, and dialysis-dependent patients, and its presence in CLI patients increases mortality by 50%, with a fivefold increase in major amputation rate.^2,3 A recent meta-analysis suggests the interrelated effects of arterial calcification and renal failure result in an increased risk of mortality and that contemporary percutaneous transluminal angioplasty (PTA) studies report sub-optimal procedural and one-year outcomes, most likely due to increased co-morbidities and adverse lesion characteristics.⁴ Additionally, medial calcification is more prevalent in below-the-knee (BTK) arteries compared to the femoropopliteal segment and is believed to contribute to arterial wall stiffness that results in the vessel recoil and restenosis seen after endovascular interventions.^2,4-6 Balloon angioplasty of BTK lesions is common and safe, yet has been shown to have insufficient long-term durability and frequently results in re-occlusion. New technologies, including drug-coated balloons (DCBs), are currently being investigated to improve effectiveness outcomes, yet current results have not proven to show a benefit. Due to these issues, clinical use of bare metal stents, drug-eluting stents, and atherectomy has extended to use in the infrapopliteal arteries for the treatment of CLI, with the goal of improving primary patency, and reducing restenosis and target lesion revascularization (TLR). Restenosis, however, continues to be an issue with these therapies, as it is a combination of both neointimal hyperplasia and recoil.

Case

A 54-year-old male presented with a non-healing ulceration on his right heel. He had past medical history significant for diabetes, end-stage renal disease on peritoneal dialysis, and a previous left BTK amputation due to a non-healing wound. Initial evaluation revealed a heavily calcified, stenotic (80%) proximal right posterior tibial vessel, 40 mm in length (Figures 1-2). Given the location of the lesion, the preferred treatment strategy was balloon angioplasty. However, given the severe concentric calcification at the lesion site, intravascular lithotripsy (IVL) was utilized with the goal of improved balloon expansion, less acute recoil, and reduced risk of flow-limiting dissection. The lesion was crossed with an .014-in Grand Slam wire (Asahi Intecc). A 3.5 mm x 60 mm IVL catheter (Shockwave Medical) was advanced and centered across the lesion. The 3.5 mm IVL balloon was inflated to 4 atmospheres (atms) and 180 pulses were administered within the lesion site (Figure 2). The IVL balloon was then inflated to 8 atms for 60 seconds. The IVL balloon was then deflated and the catheter removed. Repeat angiography was performed, showing a reduction in stenosis from 80% to less than 10%, with no evidence of acute recoil, vessel dissection, or distal embolization (Figure 3). Following the intervention, there was improved wound healing. 

Discussion

The use of intravascular lithotripsy was first described in the femoropopliteal arteries for modification of calcified plaque.⁷ IVL delivers pulsatile sonic pressure waves locally to effectively modify vascular calcium. IVL leverages similar principles to urologic lithotripsy, which has been used as a safe and effective treatment for renal calculi for several decades. Both therapies use electrohydraulic-generated sonic pressure waves that pass through soft tissue and selectively interact strongly with high-density calcium, producing significant shear stresses that have the ability to fracture the calcium. The Shockwave IVL system consists of an IV pole-mountable generator, a connector cable, and a catheter that houses an array of lithotripsy emitters enclosed in an integrated balloon (Figure 4). Using standard techniques and choice of guidewire, the IVL catheter is advanced to the lesion and placed using marker bands. The emitters along the length of the balloon create a localized field effect within the vessel to fracture both intimal and medial calcium. Following the calcium disruption, the integrated balloon is then inflated to nominal pressure to maximize luminal gain. 

This case demonstrates the feasibility and usefulness of IVL in infrapopliteal calcified stenosis to achieve improved acute results. Current treatments, including atherectomy, only address superficial calcium with varying degrees of success and result in an increased risk of vascular complications, since they do not differentiate between the calcific lesion and soft tissue. IVL is the only technology that addresses both intimal and medial calcium due to its mechanism of action. It accomplishes this by leveraging the physics of lithotripsy, which selectively differentiates calcium from soft tissue, in order to effectively modify calcium.

References 

1. Norgren L, Hiatt WR, Dormandy JA, et al.  Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II). Eur J Vasc Endovasc Surg. 2007; 33: S1-S75.
2. Guzman RJ, Brinkley DM, Schumacher PM, et al.  Tibial artery calcification as a marker of amputation risk in patients with peripheral arterial disease. J Am Coll Cardiol. 2008; 51(20): 1967-1974.
3. Huang CL, Wu IH, Wu YW, et al. Association of lower extremity arterial calcification with amputation and mortality in patients with symptomatic peripheral artery disease. PLoS One. 201426; 9(2): e90201.
4. Mustapha JA, Finton SM, Diaz-Sandoval LJ, et al. Percutaneous transluminal angioplasty in patients with infrapopliteal arterial disease: systematic review and meta-analysis. Circ Cardiovasc Interv. 2016 May; 9(5): e003468.
5. Zettervall S, Marshall A, Fleser P, et al. Association of arterial calcification with CLI in patients with PAD. J Vasc Surg. 2018; 67(2): 507-513.
6. Lanzer P, Böhm M, Sorribas V, et al. Medial vascular calcification revisited: review and perspectives. Eur Heart J. 2014; 35: 1515-1525.
7. Brodman M, Werner M, Britton T, et al. Safety and performance of lithoplasty for treatment of calcified peripheral artery lesions. J Am Coll Cardiol. 2017 Aug 15; 70(7): 908-910.

Disclosure: Dr. Mangalmurti reports he is a training proctor for Shockwave, Philips-Spectranetics, Medtronic and CSI.

Dr. Mangalmurti can be contacted via email at smangalmurti@gmail.com.