Peripheral arterial disease (PAD) is a progressive vascular condition characterized by the narrowing and calcification of peripheral arteries, leading to reduced blood flow and increased risk of critical limb ischemia (CLI) (1). In severe cases, PAD can result in major adverse events, including limb amputation, significantly impacting patients’ quality of life (2). Below-the-knee (BTK) arterial disease presents a particular challenge in endovascular treatment due to the complex nature of calcified lesions (3), which limit the efficacy of conventional therapies such as high-pressure balloon angioplasty and stenting (4). Newer technologies, such as intravascular lithotripsy (IVL), have been developed to overcome these limitations by utilizing acoustic pressure waves to fracture vascular calcium and facilitate low-pressure vessel dilatation with minimum vascular injury (5).

Despite its growing adoption in the treatment of calcified coronary and peripheral artery disease, there is a lack of real-world data on the safety and efficacy of the IVL in the Indian Patient population. Given the unique demographic and clinical characteristics of Indian PAD patients, assessing the effectiveness of IVL in this setting is crucial for optimizing treatment strategies. This study aims to evaluate the clinical outcomes of the Shockwave Peripheral IVL system for treating BTK arterial stenosis in real-world Indian patients. By focusing on both safety and effectiveness endpoints, the research seeks to provide valuable insights into the role of IVL as a viable alternative for managing complex calcified PAD cases.

Study Design

This study was designed as a retrospective, observation, single-arm, single-center study conducted at SMI Dehradun, India. The data of 25 patients were collected based on the predefined inclusion and exclusion criteria, ensuring a real-world, all-comer patient population with symptomatic PAD, including CLI. Patients included in the study had target lesions with ≥ 50% stenosis, reference vessel diameters ranging from 2.5 mm to 8.0 mm, lesion lengths of ≤200 mm, and ischemia classified as Rutherford category 1 to 6. Calcification severity was categorized as moderate when radiographic densities were visible in a single area of the vessel wall before contrast injection, while severe calcification was characterized by radiographic densities present on both sides of the arterial wall. The presence of BTK calcification was confirmed using computed tomography angiography or plain radiography. Patients with conditions such as acute limb ischemia, prior stenting at the target lesion, or major amputations were excluded from the study.

The Shockwave Peripheral IVL System was used for lithotripsy-enabled, low-pressure balloon dilation of the calcified lesions before drug-coated balloon angioplasty. The study was conducted post approval from the ethics committee and in accord with the Declaration of Helsinki, and Good Clinical Practice.

Study Device

The Shockwave peripheral intravascular lithotripsy (IVL) system is a specialized device designed for lithotripsy-enhanced, low-pressure balloon dilatation of calcified, stenotic peripheral arteries in patients requiring percutaneous therapy. The system delivers pulsatile sonic pressure waves to effectively fracture vascular calcium while minimizing vessel trauma. The primary components of the IVL system include a generator that produces 3 kV of energy, which is transmitted through a connector cable to the catheter. The catheter houses lithotripsy emitters enclosed within an integrated balloon. The balloon inflates to 4 atmospheres with a saline contrast mixture, ensuring appositions to the vessel wall and effective energy transfer. The emitters generate a series of sonic pressure waves, which pass through the fluid-filled balloon and selectively fracture both intimal and medial calcium. Once the calcium is disrupted, the balloon can be inflated to 6 atm to maximize luminal gain. The IVL catheter is suitable for treating BTK arterial stenoses.

Study Outcomes

The primary safety endpoint was determined by assessing freedom from major adverse events (MAE) within 30 days post-procedure, including mortality, emergency surgical revascularization, and limb amputation. The primary effectiveness endpoint was evaluated based on the acute reduction in target lesion diameter stenosis following the IVL procedure.

Data were collected retrospectively, with follow-up assessments performed at discharge and 30 days post-procedure. Statistical analysis was conducted using standard descriptive statistical methods, including frequency distributions for categorical variables and descriptive statistics for continuous variables.

A total of 25 patients were included in the study. The majority of patients had moderate calcification (96%), while severe calcification was observed in 4% of cases. The most commonly treated lesion locations were superficial femoral artery (36%) and popliteal artery (16%). The ankle-brachial index was recorded at 0.50 ± 0.08 pre-procedure. The demographic and clinical characteristics are shown in Table 1.

Table 1: Baseline Patient and Angiographic Characteristics

Procedural success was achieved in all cases, with 100% IVL catheter delivery success. All patients underwent balloon angioplasty pre-IVL. The mean number of IVL pulses delivered per lesion was 120.00 ± 34.64, with an inflation pressure of 4 atm. The average procedural duration was 44.60 ± 6.76 minutes, with a mean fluoroscopy time of 30.80 ± 6.56 minutes.  Contrast volume used was Visipaque 320 ml. The guiding catheter size was 6F in all cases. No stents were implanted, and post-IVL, a drug-coated balloon (Perpherics SMT) angioplasty was performed in all cases. The final angiographic characteristics have been summarized in Table 2.

Table 2: Procedure Characteristics and Angiographic Outcomes

Post-procedural angiographic outcomes demonstrated a mean post-treatment lumen diameter of 5.06 ± 1.66mm, with residual stenosis of 0-2% (mean 0.36%). No cases of dissection, perforation, distal embolization, thrombus formation, or abrupt closure were reported. Ulcer healing was observed in all patients. Primary patency was noted to be poor in all cases, but freedom from target lesion revascularization (TLR) was 100% at discharge and follow-up. No major adverse events, unplanned target limb amputations, or deaths were reported during the study period. At follow-up, target lesion patency was rated as good in all patients, shown in Table 3.

Table 3: Angiographic Outcomes and Safety Events

This study demonstrated that localized IVL with the Shockwave catheter can be performed safely and effectively in SFA and popliteal lesions. The acute results demonstrated minimal residual stenosis without relevant vascular complications or MAEs. These early outcomes in a medium to heavily calcified BTK cohort are consistent with previous studies evaluating IVL for peripheral artery disease, further reinforcing its role as a safe and effective vessel preparation strategy (6–8). The freedom from TLR in all cases at discharge and follow-up, suggests a durable early outcome following IVL in conjunction with drug-coated balloon therapy.

The BTK device was simple to use, combining the calcium disrupting capability of lithotripsy with the familiarity of traditional catheter based interventional devices. All patients in this study underwent successful IVL intervention without the need for adjunctive stenting. The procedural success was 100% without any vascular complications. The consistent performance of IVL in this study highlights its utility in treating complex calcified lesions while minimizing procedural risks.

The acute success of traditional endovascular therapies may be hampered by vessel recoil, dissection, or inadequate dilation due to the presence of heavy calcification. Previous studies have reported early recoil in up to 97% of patients treated with standard balloon angioplasty, leading to significant reductions in minimum lumen diameter and increasing the likelihood of restenosis (9,10). Long-term failure of BTK endovascular interventions remains a concern, with restenosis rates as high as 77% in some cases (4,11). In this study, the combination of IVL and drug-coated balloon provided promising early results with high patency rates at follow-up, indicating that this approach may mitigate some of the limitations associated with conventional balloon angioplasty.

Current treatment strategies for calcified arteries have resulted in an increased risk of adverse events due to their inability to differentiate between calcific lesions and soft tissue. IVL is the only technology that addresses both intimal and medial calcium while minimizing vessel injury, making it a viable alternative to traditional high-pressure balloon angioplasty or atherectomy (12). While the results from this study are encouraging, further long-term data are needed to assess the sustained benefits of IVL in BTK interventions and its role in improving clinical outcomes over time. 

Study Limitations

The study has several limitations. First, it was conducted as a single-center, observational, study with a relatively small sample size, which may limit the generalizability of the findings. Second, the follow-up period was short, preventing the assessment of long-term patency outcomes and durability of IVL therapy. Third, while IVL was consistently followed by drug-coated balloon usage, the study did not include a control group for comparison with alternative endovascular strategies such as high-pressure balloon angioplasty or atherectomy.

In conclusion, IVL demonstrated high procedural success, a favorable safety profile, and promising early clinical outcomes in the treatment of calcified below the knee arterial disease. The combination of IVL and drug-coated balloon therapy appears to be an effective strategy for optimizing vessel patency, but additional research is warranted to evaluate long-term outcomes.

Conflict in Interest: Nil

Funding: Nil

Acknowledgement: We would like to express our sincere gratitude to the staff at SGRRIHMS & SMIH for their support in data collection and management.

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