Thomas Zeller, MD, PhD
Bad Krozingen, Germany
Recent data have confirmed that an endovascular-first approach using drug-eluting technologies or endoprostheses is at least non-inferior to bypass surgery even in longer lesions. However, the major drawback of balloon angioplasty, and even of stent placement, is the potential for a suboptimal outcome due to vessel recoil as a result of extensive calcification. Calcification — medial and intimal — is present in many patients with critical limb ischemia (CLI), particularly in the elderly, patients with diabetes, and dialysis-dependent patients. A study assessing CLI patients treated with percutaneous transluminal balloon angioplasty (PTA) found that early recoil occurred in 97% of patients, resulting in a reduction in the minimum lumen diameter of 29%, which may contribute to restenosis frequently seen following PTA. Medial calcification is believed to contribute to arterial wall stiffness, which ultimately results in vessel recoil and restenosis. In a recent computed tomography (CT) angiography study, Fanelli et al demonstrated concentric calcification as being more predictive for treatment failure compared with extension in length of calcification in femoropopliteal lesions.
The Shockwave Medical Lithoplasty® System is a novel lithotripsy-enhanced balloon catheter system designed to be delivered through the peripheral arterial system of the lower extremities to the site of a calcified lesion. The Lithoplasty technology is grounded in the same fundamental principles as lithotripsy, a trusted technology used to break up kidney stones — disruption of calcified tissue using pulsatile mechanical energy designed to minimize soft tissue injury. Lithotripsy, in which calcifications are fragmented by high-power acoustic pulse waves, is a well-characterized procedure with more than 30 years of history in medicine. First introduced in the 1980s, lithotripsy was used to break up concretions such as urinary and kidney stones and is still accepted as a preferred treatment for urinary stones and gallstones. Initial safety of extracorporeal lithotripsy therapy in the peripheral vasculature has been demonstrated when utilized for improving blood flow and walking ability in patients with symptomatic peripheral arterial disease (PAD). The Shockwave Lithoptripsy technology is delivered on a standard balloon catheter platform 6 cm in length, in diameters ranging from 3.5 to 7 mm, combining the calcium-disrupting capability of lithotripsy with the familiarity of a balloon. The system, by design, uses low inflation pressures of 4 to 6 atm for vessel apposition, potentially reducing vascular injury. It utilizes semi-compliant balloon catheters with 5 lithotripsy emitters along the length of the balloon that create sonic pressure waves to disrupt calcified lesions. The device generates pulsatile mechanical energy within the target treatment site, disrupts calcium within the lesion, and allows subsequent dilation of a peripheral artery stenosis using low balloon pressure. The lithotripsy connector delivers energy from the generator to the lithotripsy electrodes located on the center shaft of the balloon. A total of 30 impulses are delivered per treatment cycle, at least 2 lithoplasty cycles are delivered per lesion segment, and the catheter expires after 6 treatment cycles and 180 shocks delivered.
The DISRUPT I and II study was designed to study the safety and effectiveness of the Shockwave Medical Lithoplasty® System in the treatment of calcified, stenotic infrainguinal peripheral arteries. It is a two-phase, prospective, nonrandomized, multicenter study including monitoring with 100% source document verification, independent angiographic and duplex ultrasound core labs, and an independent clinical events committee. Main study endpoints were procedural success, defined as <50% residual stenosis and an exploratory endpoint of a ≤30% residual stenosis. Follow-up visits were performed at 30 days, 6 months, and 12 months and analyzed major adverse events, target lesion patency by duplex ultrasound (PSVR <2.5), target lesion revascularization, and functional outcomes. Main study inclusion criteria were intermittent claudication Rutherford Classification 2 to 4, Ankle-Brachial Index ≤0.9, superficial femoral artery/popliteal artery lesions ≥70% stenosis, a reference vessel diameter 3.5 to 7.0 mm, a lesion length ≤150 mm, and moderate or severe lesion calcification by angiography.
A total of 95 patients with 95 lesions with a mean lesion length of 72 mm were included. Moderate calcification was present in 45%, and severe calcification in 55%. There were minimal adjunctive therapies, including predilatation in 11.6%, postdilatation in 7.4%, and stent implantation in 1.1% (one type IV dissection after subintimal lesion passage). Acute treatment outcomes are displayed in Figure 1, including a luminal gain of 3 mm, which is comparable to recent nitinol stent studies in lesions excluding severely calcified lesions. At 6 months, primary patency rate is 76.7% and freedom from target lesion revascularization is 96.8%. The 12-month study results will be presented in the first quarter of 2018.
As a standalone therapy, lithoplasty probably won’t overcome the limitations of balloon angioplasty regarding durability of the intervention. Therefore, it is an attractive strategy to combine a method that results in high acute treatment success (lithoplasty) with a method that improves durability of the intervention (drug-coated balloon angioplasty). The currently-enrolling DISRUPT PAD III study compares this combined treatment approach against plain balloon angioplasty, followed by drug-coated balloon angioplasty in moderate-to-severe calcified femoropopliteal lesions. In summary, the Shockwave Lithoplasty technology potentially adds a third interventional tool for the treatment of calcified femoropopliteal lesions besides atherectomy and the Supera stent technology. Further studies are mandatory to evaluate the potential role of this technology.
Thomas Zeller, MD, PhD, spoke about Lithoplasty on Tuesday, February 6, 2018 at the International Symposium on Endovascular Therapy.